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With our ML approaches, we discovered five DNA-SWNT sensors with higher fluorescence intensity response to serotonin than obtained previously. Overall, the explored ML approaches, shown to predict useful DNA sequences, can be used for discovery of DNA-based sensors and nanobiotechnologies.The SARS-CoV-2 virus has been known to gain entry into the host cell through the spike protein that binds to the host ACE2 cell surface protein. However, the role of the putative sugar-binding sites in the spike protein has remained unclear. We provide a comprehensive in silico outlook into the infection initiation wherein the virus first recognizes the sialosides on the cell via its S1A domain of the spike protein as it surfs over the cell surface. This facilitates the subsequent interaction with the cellular glycosaminoglycans through the S1B domain of the spike protein as it binds to the ACE2 receptor. The unique coadaptation to recognize both the host protein and the cell-surface carbohydrate receptors provides an additional coupling mechanism for efficient viral attachment and infection.Hafnia-based ferroelectric memory devices with excellent ferroelectricity, low power consumption, and fast operation speed have attracted considerable interest with the ever-growing desire for nonvolatile memory in flexible electronics. However, hafnia films are required to perform a high temperature (>500 °C) annealing process for crystallization into the ferroelectric orthorhombic phase. It can hinder the integration of hafnia ferroelectric films on flexible substrates including plastic and polymer, which are not endurable at high temperatures above 300 °C. Here, we propose the extremely low-temperature (∼250 °C) process for crystallization of Hf0.5Zr0.5O2 (HZO) thin films by applying a focused-microwave induced annealing method. HZO thin films on a flexible mica substrate exhibits robust remnant polarization (2Pr ∼ 50 μC/cm2), which is negligibly changed under bending tests. In addition, the electrical characteristics of a HZO capacitor on the mica substrate were evaluated, and ferroelectric thin film transistors (Fe-TFTs), using a HZO gate insulator, were fabricated on mica substrates for flexible synapse applications. Symmetric potentiation and depression characteristics are successfully demonstrated in the Fe-TFT memory devices, and the synaptic devices result in high recognition accuracy of 91.44%. The low-temperature annealing method used in this work are promising for forming hafnia-based Fe-TFT memory devices as a building block on a flexible platform.Trichoderma reesei has an extremely high capacity for synthesizing and secreting proteins, thus exhibiting promise as an expression platform for heterologous proteins. However, T. reesei secretes large amounts of native proteins, which hinders its widespread application for heterologous protein production. Here, we designed and built a series of T. reesei chassis using an iterative gene deletion approach based on an efficient genome editing system. Donor DNAs with specially designed construct facilitated screening of positive deletion strains without ectopic insertion. Finally, marker-free T. reesei chassis with lower rates of native protein secretion and low levels of extracellular protease activity were constructed after 11 consecutive rounds of gene deletion. Higher production levels of three heterologous proteins─a bacterial xylanase XYL7, a fungal immunomodulatory protein LZ8, and the human serum albumin HSA─were achieved with these chassis using the cbh1 promoter. It is possible that diverse high-value proteins might be produced at a high yield using this engineered platform.Molecular solar thermal fuels (MOSTs), especially azobenzene-based MOSTs (Azo-MOSTs), have been considered as ideal energy-storage and conversion systems in outer or confined space because of their "closed loop" properties. However, there are two main obstacles existing in practical applications of Azo-MOSTs the solvent-assistant charging process and the high molar extinction coefficient of chromophores, which are both closely related to the π-π stacking. Here, we report one efficient strategy to improve the energy density by introducing a supramolecular "cation-π" interaction into one phase-changeable Azo-MOST system. The energy density is increased by 24.7% (from 164.3 to 204.9 J/g) in Azo-MOST with a small loading amount of cation (2.0 mol %). Upon light triggering, the cation-π-enhanced Azo-MOST demonstrates one gravimetric energy density of about 56.9 W h/kg and a temperature increase of 8 °C in ambient conditions. Then the enhanced mechanism is revealed in both molecular and crystalline scales. This work demonstrates the huge potential of supramolecular interaction in the development of Azo-MOST systems, which could not only provide a universal method for enhancing the energy density of solar energy storage but also balance the conflicts between molecular design and the condensed state for phase-changeable materials.Detection and imaging of RNA at the single-cell level is of utmost importance for fundamental research and clinical diagnostics. Current techniques of RNA analysis, including fluorescence in situ hybridization (FISH), are long, complex, and expensive. Here, we report a methodology of amplified FISH (AmpliFISH) that enables simpler and faster RNA imaging using small and ultrabright dye-loaded polymeric nanoparticles (NPs) functionalized with DNA. We found that the small size of NPs (below 20 nm) was essential for their access to the intracellular mRNA targets in fixed permeabilized cells. Moreover, proper selection of the polymer matrix of DNA-NPs minimized nonspecific intracellular interactions. Optimized DNA-NPs enabled sequence-specific imaging of different mRNA targets (survivin, actin, and polyA tails), using a simple 1 h staining protocol. Encapsulation of cyanine and rhodamine dyes with bulky counterions yielded green-, red-, and far-red-emitting NPs that were 2-100-fold brighter than corresponding quantum dots. These NPs enabled multiplexed detection of three mRNA targets simultaneously, showing distinctive mRNA expression profiles in three cancer cell lines. Image analysis confirmed the single-particle nature of the intracellular signal, suggesting single-molecule sensitivity of the method. AmpliFISH was found to be semiquantitative, correlating with RT-qPCR. In comparison with the commercial locked nucleic acid (LNA)-based FISH technique, AmpliFISH provides 8-200-fold stronger signal (dependent on the NP color) and requires only three steps vs ∼20 steps together with a much shorter time. Thus, combination of bright fluorescent polymeric NPs with FISH yields a fast and sensitive single-cell transcriptomic analysis method for RNA research and clinical diagnostics.Machine learning (ML), which is becoming an increasingly popular tool in various scientific fields, also shows the potential to aid in the screening of materials for diverse applications. In this study, the computation-ready experimental (CoRE) metal-organic framework (MOF) data set for which the O2 and N2 uptakes, self-diffusivities, and Henry's constants were calculated was used to fit the ML models. The obtained models were subsequently employed to predict such properties for a hypothetical MOF (hMOF) data set and to identify structures having a high O2/N2 selectivity at room temperature. The performance of the model on known entries indicated that it would serve as a useful tool for the prediction of MOF characteristics with r2 correlations between the true and predicted values typically falling between 0.7 and 0.8. The use of different descriptor groups (geometric, atom type, and chemical) was studied; the inclusion of all descriptor groups yielded the best overall results. Only a small number of entries surpassed the performance of those in the CoRE MOF set; however, the use of ML was able to present the structure-property relationship and to identity the top performing hMOFs for O2/N2 separation based on the adsorption and diffusion selectivity.
Antipsychotic-associated weight gain is a common adverse effect with several negative outcomes in the clinical evolution of patients, which might also affect patients' self-identity from physical appearance and imply treatment discontinuation. However, recent research has drawn attention to an unexpected clinical improvement associated with weight gain, mostly in patients under treatment with clozapine or olanzapine.
Twenty-three treatment-resistant psychosis patients initiating clozapine were evaluated. Longitudinal psychopathological assessment through the Positive and Negative Syndrome Scale (PANSS) and anthropometric evaluation were performed at baseline, week 8, and 18.
Body mass index (BMI) change during clozapine treatment was associated with clinical improvement measured with PANSS total score at week 8 (P = 0.021) while showed a trend at week 18 (P = 0.058). The PANSS general score was also associated with weight gain at week 8 (P = 0.022), whereas negative subscale score showed a trend at weeksuggesting some pathophysiological mechanism underlying both conditions.
The risk of sudden cardiac death in patients receiving atypical antipsychotics may be related to QTc prolongation. The aim of this study was to investigate the risk factors for QTc prolongation to prevent QTc prolongation and guide clinical practice.
All electrocardiogram recordings of 913 schizophrenia patients who were receiving atypical antipsychotics were reviewed for prolonged QTc and associated conditions. Binary logistic regression analysis was used to investigate risk factors for QTc prolongation.
Logistic regression analysis demonstrated that sex (odds ratio [OR], 0.386; P = 0.010), age (OR, 1.047; P = 0.000), high-density lipoprotein (OR, 0.257; P = 0.014), and antipsychotics dose (OR, 1.040; P = 0.036) were significantly associated with QTc prolongation.
In patients with male sex, elder age, low high-density lipoprotein, or large antipsychotics dose, QTc should be monitored more frequently.
In patients with male sex, elder age, low high-density lipoprotein, or large antipsychotics dose, QTc should be monitored more frequently.
Tranylcypromine is the only irreversible monoamine oxidase inhibitor that is approved in the United States and in Europe for the management of treatment-resistant major depressive disorder. Comprehensive data in the literature regarding the efficacy and tolerability of tranylcypromine (TCP) combination strategies have not been systematically investigated yet.
We conducted a systematic review of available literature based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Study types considered eligible for inclusion were studies that reported information on efficacy and/or tolerability/adverse effects of pharmacological TCP add-on or coadministration strategies among people with psychiatric disorders.
Ninety-six articles were included in qualitative analyses. A relevant body of evidence shows that TCP combined with first- and second-generation antipsychotics seems relatively safe and might have beneficial effects in some patients with depressive disorders, although caution is needed with some second-generation antipsychotics that have proserotonergic activity.
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