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preferably through a complex rectal cancer MDT. Long-term sequelae such as chronic pain must be highlighted to patients. We advocate the establishment of an international registry to further record and characterise these rare, potentially troublesome lesions.A green, simple, and efficient dispersive micro-solid phase extraction method was developed for the extraction of polycyclic aromatic hydrocarbons from honey samples. In this method, for the first time, curcumin was used as an efficient and green sorbent to extract the analytes from the sample. After that the adsorbed analytes were eluted using a deep eutectic solvent prepared by mixing tetrabutylammonium chloride ethylene glycol and analyzed by gas chromatography-mass spectrometry. Important experimental factors affecting adsorption and desorption steps of the method were optimized and under optimal experimental conditions, low limits of detection (0.14-0.37 ng/g) and quantification (0.49-1.3 ng/g), wide linear range (1.3-500 ng/g) with a coefficient of determination ≥0.994 were obtained. Relative standard deviation values for intra- and interday precisions were ≤7.5% for all of the analytes at a concentration of 2 ng/g for each analyte (n = 6). Extraction recovery of the method was in the range of 72-81%. Finally, 20 honey samples were analyzed and the analytes were successfully detected. The method is environment friendly because of the use of curcumin as a sorbent. Also, biodegradability of the used deep eutectic solvent components is another advantage of the method.High humidity during harvest season often causes pre-harvest sprouting in barley (Hordeum vulgare). Prolonged grain dormancy prevents pre-harvest sprouting; however, extended dormancy can interfere with malt production and uniform germination upon sowing. In this study, we used Cas9-induced targeted mutagenesis to create single and double mutants in QTL FOR SEED DORMANCY 1 (Qsd1) and Qsd2 in the same genetic background. We performed germination assays in independent qsd1 and qsd2 single mutants, as well as in two double mutants, which revealed a strong repression of germination in the mutants. These results demonstrated that normal early grain germination requires both Qsd1 and Qsd2 function. However, germination of qsd1 was promoted by treatment with 3% hydrogen peroxide, supporting the notion that the mutants exhibit delayed germination. Likewise, exposure to cold temperatures largely alleviated the block of germination in the single and double mutants. Notably, qsd1 mutants partially suppress the long dormancy phenotype of qsd2, while qsd2 mutant grains failed to germinate in the light, but not in the dark. Consistent with the delay in germination, abscisic acid accumulated in all mutants relative to the wild type, but abscisic acid levels cannot maintain long-term dormancy and only delay germination. Elucidation of mutant allele interactions, such as those shown in this study, are important for fine-tuning traits that will lead to the design of grain dormancy through combinations of mutant alleles. Thus, these mutants will provide the necessary germplasm to study grain dormancy and germination in barley.We report on the utility of Radiofrequency Amplification by Stimulated Emission Radiation (RASER) for background-free proton detection of hyperpolarized biomolecules. We performed hyperpolarization of ~0.3 M ethyl acetate via pairwise parahydrogen addition to vinyl acetate. Proton NMR signal with signal-to-noise ratio exceeding 100,000 was detected without radio-frequency excitation at the clinically relevant magnetic field of 1.4 T using a standard (non-cryogenic) inductive detector with quality factor of Q = 68. No proton background signal was observed from protonated solvent (methanol) or other added co-solvents such as ethanol, water or bovine serum. Moreover, we demonstrate RASER detection without radio-frequency excitation of a bolus of hyperpolarized contrast agent in biological fluid. Completely background-free proton detection of hyperpolarized contrast agents in biological media paves the way to new applications in the areas of high-resolution NMR spectroscopy and in vivo spectroscopy and imaging.Ataxia-telangiectasia (A-T) is a genetic disorder caused by the lack of functional ATM kinase. A-T is characterized by chronic inflammation, neurodegeneration and premature ageing features that are associated with increased genome instability, nuclear shape alterations, micronuclei accumulation, neuronal defects and premature entry into cellular senescence. The causal relationship between the detrimental inflammatory signature and the neurological deficiencies of A-T remains elusive. Here, we utilize human pluripotent stem cell-derived cortical brain organoids to study A-T neuropathology. Mechanistically, we show that the cGAS-STING pathway is required for the recognition of micronuclei and induction of a senescence-associated secretory phenotype (SASP) in A-T olfactory neurosphere-derived cells and brain organoids. We further demonstrate that cGAS and STING inhibition effectively suppresses self-DNA-triggered SASP expression in A-T brain organoids, inhibits astrocyte senescence and neurodegeneration, and ameliorates A-T brain organoid neuropathology. Our study thus reveals that increased cGAS and STING activity is an important contributor to chronic inflammation and premature senescence in the central nervous system of A-T and constitutes a novel therapeutic target for treating neuropathology in A-T patients.
Pharmacotherapy is the primary treatment strategy in major depression. However, two-thirds of patients remain depressed after the initial antidepressant treatment. Augmented cognitive behavioral therapy (CBT) for pharmacotherapy-resistant depression in primary mental health care settings proved effective and cost-effective. 3-Methyladenine mouse Although we reported the clinical effectiveness of augmented CBT in secondary mental health care, its cost-effectiveness has not been evaluated. Therefore, we aimed to compare the cost-effectiveness of augmented CBT adjunctive to treatment as usual (TAU) and TAU alone for pharmacotherapy-resistant depression at secondary mental health care settings.
We performed a cost-effectiveness analysis at 64 weeks, alongside a randomized controlled trial involving 80 patients who sought depression treatment at a university hospital and psychiatric hospital (one each). The cost-effectiveness was assessed by the incremental cost-effectiveness ratio (ICER) that compared the difference in costs and qnts currently manifesting moderate/severe symptoms under secondary mental health care.
To find the impact of obstructive index (OI) as a predictor of management in antenatal pelviureteric junction obstruction (PUJO).
Records of 135 cases of antenatally detected unilateral PUJO, selected for initial observation were retrospectively analysed. All patients who underwent pyeloplasty on follow up were put in Group A. Those patients who were still on conservative management were put in Group B. Pelvic anteroposterior diameters of the affected [PAPD(A)] and normal kidney [PAPD(N)] of the same patient, along with the cortical thickness of the affected [CT(A)] and normal kidneys [CT(N)] on postnatal ultrasound scan and the T1/2 of the affected [T1/2 (A)] and normal kidneys [T1/2 (N)], the differential renal function (DRF) and shape of curve on diuretic renogram had been noted for each patient at 6 weeks. OI was defined as PAPD(A) X T1/2 (A) / PAPD(N) X T1/2 (N).
The median duration of follow up was 55 months (36 - 110). Median age at surgery was 12 months (4 - 80). Group A had 30 patients with 105 in Group B. On multivariate analysis, OI and shape of curve predicted need for surgery with statistical significance. Median OI in Group A was 18.9 compared to 4.82 in Group B (p<0.001, Mann- Whitney). Using ROC analysis, area under curve for OI was 0.95. A value of 12.2 could predict failure of conservative management with a sensitivity of 93.3% and a specificity of 92.4%.
The OI can reliably predict the need for surgery, at a very early stage, thus avoiding repeated tests and saving time.
The OI can reliably predict the need for surgery, at a very early stage, thus avoiding repeated tests and saving time.Mycosporine-like amino acids (MAAs) were widespread in diverse organisms to attenuate UV radiation. link2 We recently characterized the large, complicated MAA mycosporine-2-(4-deoxygadusolyl-ornithine) in desert cyanobacterium Nostoc flagelliforme. Synthesis of this MAA requires the five-gene cluster mysABDC2C3. Here, bioinformatic analysis indicated that mysC duplication within five-gene mys clusters is strictly limited to drought-tolerant cyanobacteria. Phylogenic analysis distinguished these duplicated MysCs into two clades that separated from canonical MysCs. Heterologous expression of N. flagelliforme mys genes in Escherichia coli showed that MysAB produces 4-deoxygadusol. The ATP-grasp ligase of MysC3 catalyses the linkage of the δ- or ε-amino group of ornithine/lysine to 4-deoxygadusol, yielding mycosporine-ornithine or mycosporine-lysine respectively. The ATP-grasp ligase of MysC2 strictly condenses the α-amino group of mycosporine-ornithine to another 4-deoxygadusol. link3 MysD (D-Ala-D-Ala ligase) functions following MysC2 to catalyse the formation of mycosporine-2-(4-deoxygadusolyl-ornithine). High arginine content likely provides a greater pool of ornithine over other amino acids during rehydration of desiccated N. flagelliforme. Duplication of ATP-grasp ligases is specific for the use of substrates that have two amino groups (such as ornithine) for the production of complicated MAAs with multiple chromophores. This five-enzyme biosynthesis pathway for complicated MAAs is a novel adaptation of cyanobacteria for UV tolerance in drought environments.The COVID-19 epidemic and government intervention measures may have adverse effects on people's mental health. To explore the influence of pets on the intervention of people's psychological problems during the COVID-19 epidemic, an online survey was carried out between April 9 and April 29, 2020. A total of 756 participants replied to this questionnaire. Mental health variables were assessed, and the comparison of behavior changes among pet owners and pets on positive mental well-being during COVID-19 epidemic. Comparative analysis was performed; compared with individuals without pets (n = 575), pet owners (n = 181) had a higher prevalence of insomnia (p = 0.006). Living in Wuhan city was a risk factor for people with psychological stress (p less then 0.05). Dog owners exhibited lower than average scores of insomnia and uncertainty of infection than cat owners (p = 0.004). People with more than one pet exhibited lower than average scores of depression than having one pet (p = 0.040). For analysis of psychological effects of pets on people, the role of pets in subjective feeling and positive psychological changes of pet owner was significantly different. Pet owners relieve that psychological pressure through behavioral changes towards their pets in early stage. Pets provided positive subjective well-being and psychological effects for their owners.
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