Notes

Tailored AAC Treatment to improve Engagement as well as Interaction for any Teen using Lower Affliction.
National-scale empirical models of air pollution (e.g., Land Use Regression) rely on predictor variables (e.g., population density, land cover) at different geographic scales. These models typically lack microscale variables (e.g., street level), which may improve prediction with fine-spatial gradients. We developed microscale variables of the urban environment including Point of Interest (POI) data, Google Street View (GSV) imagery, and satellite-based measures of urban form. We developed United States national models for six criteria pollutants (NO2, PM2.5, O3, CO, PM10, SO2) using various modeling approaches Stepwise Regression + kriging (SW-K), Partial Least Squares + kriging (PLS-K), and Machine Learning + kriging (ML-K). We compared predictor variables (e.g., traditional vs microscale) and emerging modeling approaches (ML-K) to well-established approaches (i.e., traditional variables in a PLS-K or SW-K framework). We found that combined predictor variables (traditional + microscale) in the ML-K models outperformed the well-established approaches (10-fold spatial cross-validation (CV) R2 increased 0.02-0.42 [average 0.19] among six criteria pollutants). Comparing all model types using microscale variables to models with traditional variables, the performance is similar (average difference of 10-fold spatial CV R2 = 0.05) suggesting microscale variables are a suitable substitute for traditional variables. ML-K and microscale variables show promise for improving national empirical models.Therapy resistance is the major cause of cancer death. As patients respond heterogeneously, precision/personalized medicine needs to be considered, including the application of nanoparticles (NPs). The success of therapeutic NPs requires to first identify clinically relevant resistance mechanisms and to define key players, followed by a rational design of biocompatible NPs capable to target resistance. Consequently, we employed a tiered experimental pipeline from in silico to analytical and in vitro to overcome cisplatin resistance. First, we generated cisplatin-resistant cancer cells and used next-generation sequencing together with CRISPR/Cas9 knockout technology to identify the ion channel LRRC8A as a critical component for cisplatin resistance. LRRC8A's cisplatin-specificity was verified by testing free as well as nanoformulated paclitaxel or doxorubicin. The clinical relevance of LRRC8A was demonstrated by its differential expression in a cohort of 500 head and neck cancer patients, correlating with patient survival under cisplatin therapy. To overcome LRRC8A-mediated cisplatin resistance, we constructed cisplatin-loaded, polysarcosine-based core cross-linked polymeric NPs (NPCis, Ø ∼ 28 nm) with good colloidal stability, biocompatibility (low immunogenicity, low toxicity, prolonged in vivo circulation, no complement activation, no plasma protein aggregation), and low corona formation properties. 2D/3D-spheroid cell models were employed to demonstrate that, in contrast to standard of care cisplatin, NPCis significantly (p less then 0.001) eradicated all cisplatin-resistant cells by circumventing the LRRC8A-transport pathway via the endocytic delivery route. We here identified LRRC8A as critical for cisplatin resistance and suggest LRRC8A-guided patient stratification for ongoing or prospective clinical studies assessing therapy resistance to nanoscale platinum drug nanoformulations versus current standard of care formulations.Herein, a new luminescent zirconium MOF [Zr-BBI, BBI = 4,4',4″,4‴-(1,4-phenylenebis(1H-imidazole-2,4,5-triyl))tetrabenzoic acid] was successfully constructed by a rationally designed functionalized bisimidazole tetracarboxylic acid ligand. Zr-BBI consists of eight-connected Zr6 clusters and four-connected BBI ligands. The high connection mode must be responsible for the high stabilities of Zr-BBI in both acidic and basic systems. Apart from the high stability, the inherent bisimidazole units endow Zr-BBI with the traits of intense fluorescent emission as well as the protonation/deprotonation behavior. Therefore, Zr-BBI could display a highly sensitive fluorescence response along with the varying pH values in the aqueous solutions and act as a pH sensing scaffold, especially in the pH value range from 4.6 to 7.12. Zr-BBI also shows good fluorescence detection performance toward Cr2O72- at a low concentration with a high KSV value up to 6.49 × 104 M-1. Moreover, by the utilization of Zr-BBI as a catalyst, Cr(VI) could be effectively photoreduced to Cr(III) in aqueous solution under visible light irradiation, in which the introduction of a hole scavenger (benzyl alcohol) could further significantly enhance the photocatalytic efficiency. Compared to that of the recently representative MOFs, the k value of the photocatalytic reaction over Zr-BBI is as high as 0.073 min-1. With the consideration of the presented results, Zr-BBI can serve as a multifunctional platform for efficiently sensing and photoreducing Cr2O72- in an aqueous system, which fully illustrates the feasibility that introducing specific functional groups in the framework of MOFs would enhance the related photocatalytic activity.Large doses and long duration are often required for herbal medicines to kill bacteria effectively. Herein, a photoacoustic interfacial engineering strategy was utilized to endow curcumin (Cur, a kind of herbal medicine) with rapid and highly effective bacteria-killing efficacy, in which Cur was combined with CuS to form a hybrid material of CuS/Cur with tight contact through in situ nucleation and growth on the petaloid CuS surface. Due to the different work functions of CuS and Cur, the interfacial electrons were redistributed, i.e., a large number of electrons gathered on the side of CuS. In contrast, the holes gathered on the side of Cur after contact. An internal electric field was formed to drive the excited electrons to transfer from CuS to Cur, thus enhancing the separation of electron-hole pairs. Besides exerting the drug nature of Cur itself, the CuS/Cur hybrid also had photo-sono responsive ability, which endowed the hybrid with photothermal, photodynamic, and sonodynamic effects. Therefore, this Cur-based hybrid killed 99.56% of Staphylococcus aureus and 99.48% of Escherichia coli under 808 nm near-infrared light irradiation and ultrasound successively for 15 min, which was ascribed to the synergy of ROS, hyperthermia, and released Cu2+ together with the drug properties of Cur. This work provides a strategy to enhance the therapeutic effects of herbal medicines against pathogenic bacterial infections by exciting the intrinsic properties of herbal medicines as materials through a photo-sono interfacial engineering strategy.The interfacial interaction including chemical bonding or electron transfer and even physisorption in composite electrocatalysts has a considerable effect on electrocatalytic oxidation reaction. Herein, we report a tremendously enhanced catalytic activity and excellent durability for the ethanol electro-oxidation reaction in NiMoO4-C-supported Pd composites (Pd/NiMoO4-C) compared to the commercial Pd/C (10%) catalyst. The X-ray powder diffraction, transmission electron microscopy, and X-ray photoelectron spectroscopy measurements disclose that the strong electron transfer between NiMoO4 nanorods and Pd nanoparticles likely induces the formation of more electrochemical active centers and improves the adsorption-desorption capacity of reactants and corresponding intermediates. In addition, the Pd/NiMoO4-C composite exhibits superior specific activity for ethanol oxidation compared to the Pd/NiMoO4 catalyst with physically incorporated carbon black, which further reveals that the stronger anchoring effect between Pd and C and higher electrical conductivity in Pd/NiMoO4-C composites are also conducive to promote the ethanol oxidation reaction. These discoveries provide an effective and simple method for the design of advanced electrocatalysts and provide more insights into optimizing the electronic interaction between the catalyst and support in general.Penta-twinned metal nanowires are finding widespread application in existing and emerging technologies. However, little is known about their growth mechanisms. We probe the origins of chloride- and alkylamine-mediated, solution-phase growth of penta-twinned Cu nanowires from first-principles using multiscale theory. Using quantum density functional theory (DFT) calculations, we characterize the binding and surface diffusion of Cu atoms on chlorine-covered Cu(100) and Cu(111) surfaces. We find stronger binding and slower diffusion of Cu atoms on chlorinated Cu(111) than on chlorinated Cu(100), which is a reversal of the trend for bare Cu surfaces. We also probe interfacet diffusion and find that this proceeds faster from Cu(100) to Cu(111) than the reverse. Using the DFT rates for hopping between individual sites at Ångstrom scales, we calculate coarse-grained, interfacet rates for nanowires of various lengths─up to hundreds of micrometers─and diameters in the 10 nm range. We predict nanowires with aspect ratios of ∼100, based on surface diffusion alone. We also account for the influence of a self-assembled alkylamine layer that covers most of the 100 facets, but is absent or thin and disordered on the 111 facets and in an "end zone" near the 100/111 boundary. With an end zone, we predict a wide range of nanowire aspect ratios in the experimental ranges. Our work reveals the mechanisms by which a halide─chloride─promotes the growth of high-aspect-ratio nanowires.Monoclonal antibody (mAb) pharmaceuticals consist of a plethora of different proteoforms with different functional characteristics, including pharmacokinetics and pharmacodynamics, requiring their individual assessment. Current binding techniques do not distinguish between coexisting proteoforms requiring tedious production of enriched proteoforms. Here, we have developed an approach based on mobility shift-affinity capillary electrophoresis-mass spectrometry (ACE-MS), which permitted us to determine the binding of coexisting mAb proteoforms to Fc receptors (FcRs). For high-sensitivity MS analysis, we used a sheathless interface providing adequate mAb sensitivity allowing functional characterization of mAbs with a high sensitivity and dynamic range. As a model system, we focused on the interaction with the neonatal FcR (FcRn), which determines the half-life of mAbs. Depending on the oxidation status, proteoforms exhibited different electrophoretic mobility shifts in the presence of FcRn, which could be used to determine their affinity. We confirmed the decrease of the FcRn affinity with antibody oxidation and observed a minor glycosylation effect, with higher affinities for galactosylated glycoforms. Next to relative binding, the approach permits the determination of individual KD values in solution resulting in values of 422 and 139 nM for double-oxidized and non-oxidized variants. Hyphenation with native MS provides unique capabilities for simultaneous heterogeneity assessment for mAbs, FcRn, and complexes formed. The latter provides information on binding stoichiometry revealing 11 and 12 for antibody/FcRn complexes. The use of differently engineered Fc-only constructs allowed distinguishing between symmetric and asymmetric binding. The approach opens up unique possibilities for proteoform-resolved antibody binding studies to FcRn and can be extended to other FcRs and protein interactions.Advances in materials chemistry and engineering serve as the basis for multifunctional neural interfaces that span length scales from individual neurons to neural networks, neural tissues, and complete neural systems. Such technologies exploit electrical, electrochemical, optical, and/or pharmacological modalities in sensing and neuromodulation for fundamental studies in neuroscience research, with additional potential to serve as routes for monitoring and treating neurodegenerative diseases and for rehabilitating patients. This review summarizes the essential role of chemistry in this field of research, with an emphasis on recently published results and developing trends. The focus is on enabling materials in diverse device constructs, including their latest utilization in 3D bioelectronic frameworks formed by 3D printing, self-folding, and mechanically guided assembly. A concluding section highlights key challenges and future directions.Two-dimensional (2D) transition-metal dichalcogenide (TMDC)-based semiconducting van der Waals (vdW) heterostructures are considered as potential candidates for next-generation nanoelectronics due to their unique and tunable properties. Controlling the carrier type and band alignment in 2D TMDCs and their vdW heterostructures is critical for realizing heterojunctions with the desired performances and functionalities. In this report, controlling the carrier type and band alignment in a vertical MoTe2/MoS2 heterojunction is presented via thickness engineering and surface charge transfer doping. A highly rectifying p-n diode and a nonrectifying n-n junction are obtained with different MoTe2 thicknesses due to their different doping conditions. A vertical tunnel diode is subsequently achieved with a controlled oxygen plasma treatment, which selectively induces degenerate p-type doping to MoTe2, whereas the intrinsic n-type characteristic of MoS2 is maintained during the treatment. These techniques to realize multifunctional diodes are universal and applicable to emerging nanoelectronics based on 2D materials.Low-temperature anion exchange membrane direct ammonia fuel cells (AEM-DAFCs) have emerged as a potential power source for transportation applications with the recognition that liquid ammonia is a carbon-free hydrogen carrier and facilitates storage, refill, and distribution. However, ammonia crossover from the cell anode to cathode can decrease the fuel efficiency, drop the voltage, and poison the cathode catalysts. In this work, the Mn-Co spinel on three different carbon supports [BP2000, Vulcan XC-72R, and multiwalled carbon nanotubes (MWCNTs)] has been successfully synthesized and demonstrated a high oxygen reduction reaction (ORR) activity with good ammonia tolerance. The structure and composition of the obtained Mn-Co-C catalysts were characterized by high-angle annular dark-field scanning transmission electron microscopy, X-ray diffraction, energy-dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy. All three catalysts exhibit superb ammonia tolerance, and Mn-Co-BP2000 demonstrates the highest ORR activity, even better than the commercial Pt-C in the presence of ammonia. When paired with the commercial PtIr-C anode, the Mn-Co-BP2000 cathode improved the peak power density of single cells from 100.1 mW cm-2 for the Pt-C cathode to 128.2 mW cm-2 under a 2 bar backpressure in both electrodes at 80 °C. All the results have manifested that Mn-Co-BP2000 is a good cathode catalyst for low-temperature AEM-DAFCs.Looking for a high-efficiency, durabile, and low-cost dual-functional oxygen electrocatalyst as the air electrode catalyst in rechargeable zinc-air batteries (ZABs) is urgently desirable but faces many challenges. Herein, we propose the preparation strategy of effectively using a bifunctional electrocatalyst (Fe-Nx/C) based on the zeolite imidazole organic framework-8 (ZIF-8) as the template agent, with surface modification coated by ferrocene (Fc) molecules followed by pyrolysis at high temperature under inert atmosphere. Benefiting from the surface modification of ZIF-8 with Fc molecules, more abundant multiple catalytic Fe/Fe-Nx/FeCx sites with high intrinsic activity are derived, the resultant Fe-Nx/C exhibits excellent potential gap (ΔE = 0.63 V) and durability, which is obviously superior to the Pt/C + IrO2 benchmark (ΔE = 0.77 V) and other state-of-the-art electrocatalysts. Furthermore, the assembled rechargeable ZABs employing the Fe-Nx/C as an air-electrode show a reduced charging-discharging potential difference of 0.603 V, high power density of 214.8 mW cm-2, and long-term cycling stability of more than 290 h at 2.0 mA cm-2. Therefore, this work presents a feasible strategy to prepare a high-efficiency and durability ORR/OER bifunctional electrocatalyst toward high performance ZABs and next-generation energy storage devices.We investigated the scalability of a previously developed growth switch based on external control of RNA polymerase expression. Our results indicate that, in liter-scale bioreactors operating in fed-batch mode, growth-arrested Escherichia coli cells are able to convert glucose to glycerol at an increased yield. A multiomics quantification of the physiology of the cells shows that, apart from acetate production, few metabolic side effects occur. However, a number of specific responses to growth slow-down and growth arrest are launched at the transcriptional level. These notably include the downregulation of genes involved in growth-associated processes, such as amino acid and nucleotide metabolism and translation. Interestingly, the transcriptional responses are buffered at the proteome level, probably due to the strong decrease of the total mRNA concentration after the diminution of transcriptional activity and the absence of growth dilution of proteins. Growth arrest thus reduces the opportunities for dynamically adjusting the proteome composition, which poses constraints on the design of biotechnological production processes but may also avoid the initiation of deleterious stress responses.Extracellular polymeric substances (EPS) are produced by many microorganisms and play an essential role in physiological systems such as nutrient storage and stress resistance. Besides, EPS show great potential in biomedical and therapeutic applications due to their biocompatibility and biodegradability. In situ noninvasive monitoring of the EPS produced by microorganisms is thus critical but has not yet been achieved. Herein, we developed a novel aggregation-induced emission (AIE) active nanoprobe enabling in situ visualization of the EPS distribution produced by various microorganisms (cyanobacteria, yeast, freshwater, and marine phytoplankton). The synthesized AIE-active nanoprobe displayed excellent specificity and precision for the staining of EPS, as well as strong photostability, showing great advantage in sensing the EPS in living organisms. With the application of this novel probe, the three-dimensional (3D) framework of EPS distribution was visualized under different environmental conditions (temperature, light intensity, nutrition, and pH). The EPS distribution was found to correlate significantly with the metal tolerance and cyanobacterial photosynthesis capability. Collectively, this study proposed an AIE-active nanoprobe for visualizing the EPS distribution and quantifying the EPS thickness/volume, and has significant implications in understanding the physiological functions of microorganisms.Polycyclic aromatic hydrocarbons (PAHs) are among the most toxic and bioavailable components found in petroleum and represent a high risk to aquatic organisms. The aryl hydrocarbon receptor (Ahr) is a ligand-activated transcription factor that mediates the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other planar aromatic hydrocarbons, including certain PAHs. Ahr acts as a xenosensor and modulates the transcription of biotransformation genes in vertebrates, such as cytochrome P450 1A (cyp1a). Atlantic cod (Gadus morhua) possesses two Ahr proteins, Ahr1a and Ahr2a, which diverge in their primary structure, tissue-specific expression, ligand affinities, and transactivation profiles. Here, a luciferase reporter gene assay was used to assess the sensitivity of the Atlantic cod Ahrs to 31 polycyclic aromatic compounds (PACs), including two- to five-ring native PAHs, a sulfur-containing heterocyclic PAC, as well as several methylated, methoxylated, and hydroxylated congeners. Notably, most parent compounds, including naphthalene, phenanthrene, and partly, chrysene, did not act as agonists for the Ahrs, while hydroxylated and/or alkylated versions of these PAHs were potent agonists. Importantly, the greater potencies of substituted PAH derivatives and their ubiquitous occurrence in nature emphasize that more knowledge on the toxicity of these environmentally and toxicologically relevant compounds is imperative.Iron (Fe) plays important roles in both essential cellular processes and virulence pathways for many bacteria. Consequently, Fe withholding by the human innate immune system is an effective form of defense against bacterial infection. In this Perspective, we review recent studies that have established a foundation for our understanding of the impact of the metal-sequestering host defense protein calprotectin (CP) on bacterial Fe homeostasis. We also discuss two recently uncovered strategies for bacterial adaptation to Fe withholding by CP. Together, these studies provide insight into how Fe sequestration by CP affects bacterial pathogens that include Pseudomonas aeruginosa, Acinetobacter baumannii, and Staphylococcus aureus. Overall, recent studies suggest that Fe withholding by CP may have implications for bacterial survival and virulence in the host, and further explorations that directly address this possibility present an important area for discovery.Tungsten carbide (W2C) has emerged as a potential alternative to noble-metal catalysts toward hydrogen evolution reaction (HER) owing to its Pt-like electronic configuration. However, unsatisfactory activity, dilatory electron transfer, and inefficient synthesizing methods, especially for nanoscale particles, have severely hindered its large-scale applications. Herein, a novel heterostructure composed of W2C and tungsten phosphide (WP) embedded in nitrogen-decorated carbon (W2C/WP@NC) was constructed as an efficient HER electrocatalyst. The as-prepared W2C/WP@NC catalyst exhibits remarkable electrocatalytic activity and robust durability toward HER both in acids and bases. More notably, the W2C/WP@NC catalyst demonstrates low overpotentials of 116.37 and 196.2 mV to afford a current density of 10 mA cm-2 and reveals slight potential decays of about 6.4 and 7.64% over 12 h continuous operation in bases and acids, respectively. The overall water-splitting performance was further evaluated using the W2C/WP@NC catalyst as the cathode and commercial RuO2 as the anode in an electrolyzer, which can realize an overall current density of 10 mA cm-2 and maintain long durability of more than 12 h with a small cell voltage of 1.723 V. This work opens up new opportunities for exploring cost-efficient electrocatalysts in sustainable energy conversion.Access to the potential applications of metal-organic frameworks (MOFs) depends on rapid fabrication. While there have been advances in the large-scale production of single-component MOFs, rapid synthesis of multicomponent MOFs presents greater challenges. Multicomponent systems subjected to rapid synthesis conditions have the opportunity to form separate kinetic phases that are each built up using just one linker. We sought to investigate whether continuous flow chemistry could be adapted to the rapid formation of multicomponent MOFs, exploring the UMCM-1 and MUF-77 series. Surprisingly, phase pure, highly crystalline multicomponent materials emerge under these conditions. To explore this, in situ WAXS was undertaken to gain an understanding of the formation mechanisms at play during flow synthesis. Key differences were found between the ternary UMCM-1 and the quaternary MUF-7, and key details about how the MOFs form were then uncovered. Counterintuitively, despite consisting of just two ligands UMCM-1 proceeds via MOF-5, whereas MUF-7 consists of three ligands but is generated directly from the reaction mixture. By taking advantage of the scalable high-quality materials produced, C6 separations were achieved in breakthrough settings.In this work, we demonstrate a 3-dimensional graphene oxide (3D GO) stalk that operates near the capillary wicking limit to achieve an evaporation flux of 34.7 kg m-2 h-1 under 1 sun conditions (1 kW/m2). This flux represents nearly a 100 times enhancement over a conventional solar evaporation pond. Interfacial solar evaporation traditionally uses 2D evaporators to vaporize water using sunlight, but their low evaporative water flux limits their practical applicability for desalination. Some recent studies using 3D evaporators demonstrate potential for more efficient water transfer, but the flux improvement has been marginal because of a low evaporation area index (EAI), which is defined as the ratio of the total evaporative surface area to the projected ground area. By using a 3D GO stalk with an ultrahigh EAI of 70, we achieved nearly a 20-fold enhancement over a 2D GO evaporator. The 3D GO stalk also exhibited additional advantages including omnidirectional sunlight utilization, a high evaporation flux under dark conditions from more efficient utilization of ambient heating, a dramatic increase of the evaporation rate by introducing wind, and scaling resistance in evaporating brines with a salt content of up to 17.5 wt %. This performance makes the 3D GO stalk well suited for the development of a low-cost, reduced footprint technology for zero liquid discharge in brine management applications.NASICON-type Li1+xAlxTi2-x(PO4)3 (LATP) is a promising solid electrolyte (SE) candidate for next-generation solid-state batteries. However, its use in solid-state composite electrodes is inhibited by its stiffness, which results in poor interparticle contact unless high-temperature treatments are applied. The poor LATP-LATP and LATP-active material in the positive electrode (cathode) composite produced at ambient temperature yield poor ionic conductivity, impeding the electrode's performance. Herein, we focus on the optimization of the electrochemical performance of LiNi0.8Co0.1Mn0.1O2 (NCM811)-LATP composite electrodes made by tape casting, taking advantage of a small fraction of an ionic liquid electrolyte (ILE) filling the composite cathode porosity. The incorporated LATP particles are found to closely surround the large NCM811 secondary particles, partially filling the composite electrode pores and resulting in a porosity reduction from 37 vol % (NCM811 only) to 32 vol % (NCM811-LATP). After filling up the majority of the electrode porosity with ILE, the NCM811-LATP composite electrodes offer improved capacity retention upon both long-term cycling tests (>99.3% after 200 cycles) and high-rate tests (>70% at 2 C-rate), due to the more stable LATP|NCM811 interface, and facilitated Li+ diffusion in the composite electrode bulk. Results obtained from proof-of-concepts monopolar (3.0-4.3 V) and bipolar-stacked (6.0-8.6 V) cells are reported.Dental diseases resulting from movement disorders and volatile gases are very common. The classic method for detecting occlusal force is effective; however, its function is one-time rather than real-time monitoring, and the technology is very time-consuming. Herein, we report a multifunctional, flexible, and degradable bacterial cellulose/Ti3C2Tx MXene bioaerogel for the accurate detection of occlusal force and early diagnosis of periodontal diseases. Combining the mechanical properties of MXene and the abundant functional groups of bacterial cellulose, 3D porous bioaerogels exhibit both pressure-sensitive and ammonia (NH3)-sensitive responses. By integrating these substances into a flexible array, the resulting device can distinguish the intensity, location, and even the time sequence of the occlusion force; moreover, it can provide NH3 gas and occlusion force response signals. Therefore, this technology is promising for both disease diagnosis and oral health. In addition, the introduction of a renewable biomaterial allows the bioaerogel to degrade completely using a low-concentration hydrogen peroxide solution, making the device environmentally friendly and satisfying the demands for sustainable development.Microalgae are emerging as next-generation renewable resources for production of sustainable biofuels and high-value bioproducts. Conventional microalgae harvesting methods including centrifugation, filtration, flocculation, and flotation are limited by intensive energy consumption, high capital cost, long treatment time, or the requirement of chemical addition. In this study, we design and fabricate porous superabsorbent polymer (PSAP) beads for self-driven 3D microfiltration of microalgal cultures. The PSAP beads can swell fast in a microalgal suspension with high water absorption capacity. During this process, microalgal cells are excluded outside the beads and successfully concentrated in the residual medium. After treatment, the beads can be easily separated from the microalgal concentrate and reused after dewatering. In one PSAP treatment, a high concentration factor for microalgal cultures up to 13 times can be achieved in 30 min with a harvesting efficiency higher than 90%. Furthermore, microalgal cultures could be concentrated from 0.2 g L-1 to higher than 120 g L-1 with minimal biomass loss through multistage PSAP treatments. Therefore, the use of PSAP beads for microalgae harvesting is fast, effective, and scalable. It does not require any complex instrument or chemical addition. This technique potentially provides an efficient and feasible alternative to obtain high concentrations of functional biomass at a very low cost.Knowledge of the distribution and dissemination of antibiotic resistance genes (ARGs) is essential for understanding anthropogenic impacts on natural ecosystems. The transportation of ARGs via aquatic environments is significant and has received great attention, but whether there has been anthropogenic ARG pollution to the hadal ocean ecosystem has not been well explored. For investigating ecological health concerns, we profiled the ARG occurrence in sediments of the Mariana Trench (MT) (10 890 m), the deepest region of the ocean. Metagenomic-based ARG profiles showed a sudden increase of abundance and diversity in the surface layer of MT sediments reaching 2.73 × 10-2 copy/cell and 81 subtypes, and a high percentage of ∼63.6% anthropogenic pollution sources was predicted by the Bayesian-modeling classification method. These together suggested that ARG accumulation and anthropogenic impacts have already permeated into the bottom of the deepest corner on the earth. Moreover, six ARG-carrying draft genomes were retrieved using a metagenomic binning strategy, one of which assigned as Streptococcus was identified as a potential bacterial host to contribute to the ARG accumulation in MT, carrying ermF, tetM, tetQ, cfxA2, PBP-2X, and PBP-1A. We propose that the MT ecosystem needs further long-term monitoring for the assessment of human impacts, and our identified three biomarkers (cfxA2, ermF, and mefA) could be used for the rapid monitoring of anthropogenic pollution. Together our findings imply that anthropogenic pollution has penetrated into the deepest region of the ocean and urge for better pollution control to reduce the risk of ARG dissemination to prevent the consistent accumulation and potential threat to the natural environment.Metallic transition-metal dichalcogenides (TMDs) are rich material systems in which the interplay between strong electron-electron and electron-phonon interactions often results in a variety of collective electronic states, such as charge density waves (CDWs) and superconductivity. While most metallic group V TMDs exhibit coexisting superconducting and CDW phases, 2H-NbS2 stands out with no charge ordering. Further, due to strong interlayer interaction, the preparation of ultrathin samples of 2H-NbS2 has been challenging, limiting the exploration of presumably rich quantum phenomena in reduced dimensionality. Here, we demonstrate experimentally and theoretically that light substitutional doping of NbS2 with heavy atoms is an effective approach to modify both interlayer interaction and collective electronic states in NbS2. Very low concentrations of Re dopants ( less then 1%) make NbS2 exfoliable (down to monolayer) while maintaining its 2H crystal structure and superconducting behavior. In addition, first-principles calculations suggest that Re dopants can stabilize some native CDW patterns that are not stable in pristine NbS2.Fluorine (F) atoms with the highest electronegativity and low polarizability can easily modify the surface and composition of carbon-based electrode materials. However, this is accompanied by complete irreversibility and uncontrolled reactivity, thus hindering their use in rechargeable electronic devices. Therefore, understanding the electrochemical effects of the C-F configuration might lead to achieving superior electrochemical properties. Here, we demonstrate that the fluorinated and simultaneously reduced graphene oxide (FrGO) was easily synthesized through direct gas fluorination. The as-prepared 11%-FrGO electrode exhibited a high capacity (1365 mAh g-1 at 0.1 A g-1), remarkable rate capability, and good stability (64% retention after 1000 cycles at 5 A g-1). Furthermore, the annealed FrGO (11%-FrGO(A)) electrode in which the C-F bond configurations were controlled by facile thermal treatment shows long-term stability (80% retention after 1000 cycles at 5 A g-1). Above a certain content, F atoms enhance Li-ion adsorption and electron transfer, accelerate Li-ion diffusion, and facilitate the formation of a solid electrolyte interphase layer. In particular, the C-F configuration plays a significant role in retaining the capacity under harsh recharging conditions. The results in this study could provide valuable insights into the field of rechargeable devices.Highly efficient elimination of petroleum pollution is of great importance for addressing environmental issues and social sustainability. In this study, we demonstrate a novel strategy for efficient elimination of petroleum pollution by selective adsorption of it by an ultralight hydrophobic/lipophilic microorganism-loaded biomass porous foam (BTS-MSFT4@MTMS) followed by a green degradation of adsorbates under mild conditions. The porous structure of biomass porous foam (MSFT) could provide plenty of room for immobilization of Bacillus thuringiensis (BTS), while a simple surface modification of the MSFT load with a BTS strain (BTS-MSFT4) by methyltrimethoxysilane (MTMS) could change its wettability from hydrophilic to lipophilic, which makes selective adsorption of hydophobic petroleum pollution from water for biodegradation possible. As expected, using a petroleum n-hexadecane solution with a concentration of 3% as a model oily wastewater, the as-prepared BTS-MSFT4@MTMS possesses both a superior selective adiodegradation into biodegradable BTS-MSFT4@MTMS may particularly have great potential for practical application in environmental remediation.Polydopamine (PDA) has been widely used in biomedical applications including imaging contrast agents, antioxidants, UV protection, and photothermal therapy due to its biocompatibility, metal-ion chelation, free-radical scavenging, and wideband absorption, but its low photothermal efficiency still needs to be improved. In this study, we chelated near-infrared (NIR) sensitive carbon quantum dots on the surface of polydopamine (PDA-PEI@N,S-CQDs) to increase its near-infrared absorption. Surprisingly, although only 4% (w/w) of carbon quantum dots was conjugated on the PDA surface, it still increased the photothermal efficiency by 30%. Moreover, PDA-PEI@N,S-CQDs could also be used as the drug carrier for loading 60% (w/w) of the DOX and achieved stimuli-responsive drug release under lysosomal pH (pH 5.0) and 808 nm laser illumination. For in vitro therapeutic experiment, PDA-PEI@N,S-CQDs showed the remarkable therapeutic performance under 808 nm laser irradiation for killing 90% of cancer cells compared with 50% by pure PDA nanoparticles, and the efficacy was even higher after loading DOX owing to the synergistic effect by photothermal therapy and chemotherapy. This intelligent and effective therapeutic nanosystem based on PDA-PEI@N,S-CQDs showed enhanced photothermal behavior after chelating carbon dots and promoted the future development of a nanoplatform for stimuli-responsive photothermal/chemo therapy.
Little evidence has been available to support the use of thiazide diuretics to treat hypertension in patients with advanced chronic kidney disease.

We randomly assigned patients with stage 4 chronic kidney disease and poorly controlled hypertension, as confirmed by 24-hour ambulatory blood-pressure monitoring, in a 11 ratio to receive chlorthalidone at an initial dose of 12.5 mg per day, with increases every 4 weeks if needed to a maximum dose of 50 mg per day, or placebo; randomization was stratified according to previous use of loop diuretics. The primary outcome was the change in 24-hour ambulatory systolic blood pressure from baseline to 12 weeks. Secondary outcomes were the change from baseline to 12 weeks in the urinary albumin-to-creatinine ratio, N-terminal pro-B-type natriuretic peptide level, plasma renin and aldosterone levels, and total body volume. Safety was also assessed.

A total of 160 patients underwent randomization, of whom 121 (76%) had diabetes mellitus and 96 (60%) were receiving leases in serum creatinine level, hyperglycemia, dizziness, and hyperuricemia occurred more frequently in the chlorthalidone group than in the placebo group.

Among patients with advanced chronic kidney disease and poorly controlled hypertension, chlorthalidone therapy improved blood-pressure control at 12 weeks as compared with placebo. (Funded by the National Heart, Lung, and Blood Institute and the Indiana Institute of Medical Research; CLICK ClinicalTrials.gov number, NCT02841280.).
Among patients with advanced chronic kidney disease and poorly controlled hypertension, chlorthalidone therapy improved blood-pressure control at 12 weeks as compared with placebo. (Funded by the National Heart, Lung, and Blood Institute and the Indiana Institute of Medical Research; CLICK ClinicalTrials.gov number, NCT02841280.).
Daprodustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor. In patients with chronic kidney disease (CKD) who are not undergoing dialysis, the efficacy and safety of daprodustat, as compared with the conventional erythropoiesis-stimulating agent darbepoetin alfa, are unknown.

In this randomized, open-label, phase 3 trial with blinded adjudication of cardiovascular outcomes, we compared daprodustat with darbepoetin alfa for the treatment of anemia in patients with CKD who were not undergoing dialysis. The primary outcomes were the mean change in the hemoglobin level from baseline to weeks 28 through 52 and the first occurrence of a major adverse cardiovascular event (MACE; a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke).

Overall, 3872 patients were randomly assigned to receive daprodustat or darbepoetin alfa. The mean (±SD) baseline hemoglobin levels were similar in the two groups. The mean (±SE) change in the hemoglobin level from baseline to weialysis, daprodustat was noninferior to darbepoetin alfa with respect to the change in the hemoglobin level from baseline and with respect to cardiovascular outcomes. (Funded by GlaxoSmithKline; ASCEND-ND ClinicalTrials.gov number, NCT02876835.).
Among patients with chronic kidney disease (CKD), the use of recombinant human erythropoietin and its derivatives for the treatment of anemia has been linked to a possibly increased risk of stroke, myocardial infarction, and other adverse events. Several trials have suggested that hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors (PHIs) are as effective as erythropoiesis-stimulating agents (ESAs) in increasing hemoglobin levels.

In this randomized, open-label, phase 3 trial, we assigned patients with CKD who were undergoing dialysis and who had a hemoglobin level of 8.0 to 11.5 g per deciliter to receive an oral HIF-PHI (daprodustat) or an injectable ESA (epoetin alfa if they were receiving hemodialysis or darbepoetin alfa if they were receiving peritoneal dialysis). The two primary outcomes were the mean change in the hemoglobin level from baseline to weeks 28 through 52 (noninferiority margin, -0.75 g per deciliter) and the first occurrence of a major adverse cardiovascular event (a compositeaprodustat was noninferior to ESAs regarding the change in the hemoglobin level from baseline and cardiovascular outcomes. (Funded by GlaxoSmithKline; ASCEND-D ClinicalTrials.gov number, NCT02879305.).
Among patients with CKD undergoing dialysis, daprodustat was noninferior to ESAs regarding the change in the hemoglobin level from baseline and cardiovascular outcomes. (Funded by GlaxoSmithKline; ASCEND-D ClinicalTrials.gov number, NCT02879305.).Monoubiquitination of histone H2B at lysine 120 plays a vital role in active transcription and DNA damage response pathways. UBR7 has been recently identified as an H2BK120 monoubiquitin ligase. However, the molecular details of its ubiquitin transfer mechanism are not well understood. Here, we report that PHD finger of UBR7 is essential for its association with E2 UbcH6 and consequent ubiquitin transfer to its substrate histone H2B. We have also identified the critical region of UbcH6 involved in this function and shown that the residues stretching from 114 to 125 of histone H2B C-terminal tail are sufficient for UBR7/UbcH6-mediated ubiquitin transfer. We also employed antibody-independent mass spectrometry to confirm UBR7 mediated ubiquitination of H2B C-terminal tail. We have demonstrated that the PHD finger of UBR7 forms a dimer and this dimerization is essential for ubiquitination of histone H2B. We have mapped the critical residues involved in dimerization and mutation of these residues abrogates E3 ligase activity and is associated with cancer. Furthermore, we have compared the mode of ubiquitin discharge from UbcH6 mediated by UBR7 and RNF20 through thioester hydrolysis assay. Interestingly, binding of substrate H2B to UBR7 induces conformational change in the PHD finger, which triggers ubiquitin transfer from UbcH6. However RNF20 RING finger alone is sufficient to promote the release of ubiquitin from UbcH6. Overall, the mechanism of ubiquitin transfer by the newly identified E3 ubiquitin ligase UBR7 is markedly different from that of RNF20.
Ribociclib, one of the cyclin-dependent kinases (CDK) 4 and 6 inhibitors, in combination with endocrine therapies has been approved in the treatment of hormonal receptor positive, HER-2 negative metastatic breast cancer worldwide. Long-term usage of ribociclib with concomitant drugs, potential drug-drug interaction may develop which can limit the therapeutic value of CDK4/6 inhibitor.

A 62-year-old with history of non-insulin dependent diabetic, dyslipidemia, and essential hypertension was diagnosed with HR-positive, HER-2 negative metastatic breast cancer and treated with fulvestrant plus ribociclib. Four weeks after administration, elevated serum creatinine was observed, and then severe lactic acidosis with acute respiratory failure was subsequently reported. Ribociclib and fulvestrant were temporarily discontinued. Three days after renal replacement therapy, her clinical was stabilized. Combination ribociclib with metformin resulted in high plasma metformin levels and dangerous consequences. Hence, special precaution should be considered during concomitant treatment with sensitive transporter substrates.

Metformin associated lactic acidosis may potentially occur after combination with ribocilib, an uncommon but lethal complication from the interaction of these drugs, especially in patients who had preexisting renal impairment.
Metformin associated lactic acidosis may potentially occur after combination with ribocilib, an uncommon but lethal complication from the interaction of these drugs, especially in patients who had preexisting renal impairment.
Despite high rates of medication non-adherence among patients with systemic lupus erythematosus (SLE), effective interventions to improve adherence in SLE are limited. We aimed to assess the feasibility of a pilot intervention and explore its effect on adherence (clinicaltrials.gov identifier NCT03738826).

The intervention used pharmacy refill data to monitor non-adherence and prompt discussions surrounding SLE medications during clinic encounters. Over 12 weeks, the intervention was delivered through routine clinic visits by providers to patients with SLE who take SLE-specific medications. We measured acceptability, appropriateness, and feasibility using provider surveys. We also measured acceptability by patient surveys and feasibility by medical record documentation. We explored change in adherence by comparing percent of patients with medication possession ratio (MPR) ≥80% three months before and after the intervention visit using the McNemar's test.

Six rheumatologists participated; 130 patients we intervention, assess its efficacy in a controlled setting, and adapt its use among other clinic settings. This article is protected by copyright. All rights reserved.
Glucose metabolic disorder is the main cause for type 2 diabetes mellitus (T2DM) progression. Exploring the molecular mechanisms of metabolic disorder are crucial for T2DM treatment.

MicroRNA (miR)-363, NOTCH1 and forkhead box C2 (FOXC2) expressions in high glucose (HG)-treated HepG2 cells and the livers of T2DM rats were assessed using qPCR. Protein levels of NOTCH1, FOXC2 and phosphatidylinositol 3-kinase (PI3K)/serine/threonine protein kinase (Akt)-related proteins were evaluated using western blot. Lipid accumulation was determined using Oil Red O staining. Then glucose consumption, blood glucose level and glycogen content were detected using kits. Finally, dual luciferase reporter assay was employed to verify the binding relationship between miR-363 and NOTCH1, and the binding relationship between miR-363 and FOXC2.

MiR-363 was significantly upregulated in the livers of diabetic rats and HG-induced HepG2 cells, while NOTCH1 and FOXC2 were downregulated. In HG-induced HepG2 cells, miR-363 inhibitor markedly increased glucose consumption and uptake, and reduced accumulation of lipid droplets. Then NOTCH1 and FOXC2 were identified as downstream targets of miR-363. NOTCH1 overexpression or FOXC2 overexpression could ameliorate glucose and lipids metabolism disorder in T2DM model cells. In addition, we found that FOXC2 inhibition abolished the effect of NOTCH1 overexpression on HG-induced HepG2 cells. Finally, we proved that PI3K/AKT pathway was the downstream pathway of FOXC2.

MiR-363 was considered as a key regulator of glucose and lipids metabolism in T2DM, which regulated PI3K/AKT axis by targeting NOTCH1 and FOXC2, thus leading to hepatic glucose and lipids metabolism disorder in T2DM.
MiR-363 was considered as a key regulator of glucose and lipids metabolism in T2DM, which regulated PI3K/AKT axis by targeting NOTCH1 and FOXC2, thus leading to hepatic glucose and lipids metabolism disorder in T2DM.Glioma is the predominant brain malignancy and is correlated with high mortality and severe morbidity. The transcription factor Limb-bud and heart (LBH) has been reported to be involved in the development of several cancers, but its role in glioma development remains elusive. Here, we examined the effect of LBH on glioma progression. The expression of LBH was increased in glioma samples from TCGA database, and up-regulation of LBH was observed to be correlated with the poor survival of glioma patients. We also report that expression of LBH was elevated in clinical glioma tissues compared with the adjacent normal tissues, and was also enhanced in glioma cell lines. LBH promotes proliferation and inhibits cell cycle arrest and apoptosis in glioma cells. In addition, LBH increased the migration and invasion of glioma cells in vitro. Moreover, tumorigenicity analysis revealed that LBH could promote the tumor growth of glioma cells in vivo. In conclusion, our findings suggest that LBH contributes to glioma progression in vitro and in vivo. Our findings provides new insights into the mechanism by which LBH promotes the development of glioma, improving our understanding of the correlation between LBH with cancer. LBH may have potential as a target for glioma therapy.Lipid metabolism is essential for stemness maintenance, self-renewal, and differentiation of stem cells, however, the regulatory function of cholesterol metabolism in erythroid differentiation is poorly studied. In the present study, a critical role for cholesterol homeostasis in terminal erythropoiesis is uncovered. The master transcriptional factor GATA1 binds to Sterol-regulatory element binding protein 2 (SREBP2) to downregulate cholesterol biosynthesis, leading to a gradual reduction in intracellular cholesterol levels. It is further shown that reduced cholesterol functions to block erythroid proliferation via the cholesterol/mTORC1/ribosome biogenesis axis, which coordinates cell cycle exit in the late stages of erythroid differentiation. The interaction of GATA1 and SREBP2 also provides a feedback loop for regulating globin expression through the transcriptional control of NFE2 by SREBP2. Importantly, it is shown that disrupting intracellular cholesterol hemostasis resulted in defect of terminal erythroid differentiation in vivo. These findings demonstrate that fine-tuning of cholesterol homeostasis emerges as a key mechanism for regulating erythropoiesis.Loss of the mitochondrial fission enzyme dynamin-related protein 1 (Drp1) in cardiomyocytes results in energy shortage and heart failure. We aim to understand the intracellular signal pathway and extracellular factors regulating Drp1 phosphorylation and mitochondrial morphology and function in cardiomyocytes. We found cyclic mechanical stretching induced mitochondrial fission through Drp1 and focal adhesion kinase (FAK) in neonatal rat ventricular myocytes (NRVMs). FAK regulated phosphorylation of Drp1 and mitochondrial Drp1 levels. Extracellular fibronectin activated Drp1 and caused mitochondrial fission through FAK and extracellular signal-regulated kinase 1/2 (ERK1/2). Fibronectin increased NRVMs oxygen consumption rate and ATP content via FAK-ERK1/2-Drp1. Inhibition of the FAK-ERK1/2-Drp1 pathway caused cellular energy shortage. In addition, the FAK-ERK1/2-Drp1 pathway was rapidly activated by adrenergic agonists and contributed to agonists-stimulated NRVMs respiration. Interestingly, fibronectin limited the adrenergic agonists-induced NRVMs respiration by restricting phosphorylation of Drp1. Our results suggest that extracellular fibronectin and adrenergic stimulations use the FAK-ERK1/2-Drp1 pathway to regulate mitochondrial morphology and function in cardiomyocytes.
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