Critical patients with the coronavirus disease 2019 (COVID-19), even those whose nucleic acid test results had turned negative and those receiving maximal medical support, have been noted to progress ...to irreversible fatal respiratory failure. Lung transplantation (LT) as the sole therapy for end-stage pulmonary fibrosis related to acute respiratory distress syndrome has been considered as the ultimate rescue therapy for these patients.
From February 10 to March 10, 2020, three male patients were urgently assessed and listed for transplantation. After conducting a full ethical review and after obtaining assent from the family of the patients, we performed three LT procedures for COVID-19 patients with illness durations of more than one month and extremely high sequential organ failure assessment scores.
Two of the three recipients survived post-LT and started participating in a rehabilitation program. Pearls of the LT team collaboration and perioperative logistics were summarized and continually improved. The pathological results of the explanted lungs were concordant with the critical clinical manifestation, and provided insight towards better understanding of the disease. Government health affair systems, virology detection tools, and modern communication technology all play key roles towards the survival of the patients and their rehabilitation.
LT can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis. If confirmed positive-turned-negative virology status without organ dysfunction that could contraindicate LT, LT provided the final option for these patients to avoid certain death, with proper protection of transplant surgeons and medical staffs. By ensuring instant seamless care for both patients and medical teams, the goal of reducing the mortality rate and salvaging the lives of patients with COVID-19 can be attained.
Human infection with the novel avian-origin influenza A (H7N9) virus has aroused global concern. In this report, the clinical characteristics of 111 laboratory-confirmed cases in China are presented.
...On March 30, 2013, three patients with fatal cases of rapid, progressive pneumonia were confirmed to be infected with a novel avian-origin influenza A (H7N9) virus that had not been detected in humans and animals previously.
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The new human H7N9 viruses are the product of reassortment of viruses that are of avian origin.
Global attention was soon focused on the situation because of the increasing number of new cases and the high rate of death associated with these infections.
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As of May 9, the World Health Organization (WHO) had reported 131 laboratory-confirmed cases, including 32 deaths.
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However, data on . . .
The methylotrophic yeast Pichia pastoris (Komagataella phaffii) is a highly distinguished expression platform for the excellent synthesis of various heterologous proteins in recent years. With the ...advantages of high‐density fermentation, P. pastoris can produce gram amounts of recombinant proteins. While not every protein of interest can be expressed to such high titers, such as Baeyer–Villiger monooxygenase (BVMO) (AcPSMO) which is responsible for pyrazole sulfide asymmetric oxidation. In this work, an excellent yeast expression system was established to facilitate efficient AcPSMO expression, which exhibited 9.5‐fold enhanced secretion. Subsequently, an ultrahigh throughput screening method based on fluorescence‐activated cell sorting by fusing super folder green fluorescent protein (sfGFP) in the C‐terminal of AcPSMO was developed, and directed evolution was performed. The protein expression level of the superior mutant AcPSMOP1 (S58T/T252P/E336N/H456D) reached 84.6 mg/L at 100 mL shaking flask, which was 4.7 times higher than the levels obtained with the wild‐type. Finally, the optimized chassis cells were used for high‐density fermentation on a 5‐L scale, and AcPSMOP1 protein yield of 3.4 g/L was achieved, representing approximately 85% of the total protein secreted. By directly employing the pH‐adjusted supernatant as a biocatalyst, 20 g/L pyrmetazole sulfide was completely transformed into the corresponding (S)‐sulfoxide, with a 78.8% isolated yield. This work confers dramatic benefits for efficient secretion of other BVMOs in P. pastoris.
A platform for efficient secretion of BVMO in P. pastoris was established.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Nuclear factor Y (NF-Y) is a ubiquitous transcription factor composed of three distinct subunits (NF-YA, NF-YB, and NF-YC). We found that the Arabidopsis thaliana NFYA5 transcript is strongly induced ...by drought stress in an abscisic acid (ABA)-dependent manner. Promoter:β-glucuronidase analyses showed that NFYA5 was highly expressed in vascular tissues and guard cells and that part of the induction by drought was transcriptional. NFYA5 contains a target site for miR169, which targets mRNAs for cleavage or translational repression. We found that miR169 was downregulated by drought stress through an ABA-dependent pathway. Analysis of the expression of miR169 precursors showed that miR169a and miR169c were substantially downregulated by drought stress. Coexpression of miR169 and NFYA5 suggested that miR169a was more efficient than miR169c at repressing the NFYA5 mRNA level. nfya5 knockout plants and plants overexpressing miR169a showed enhanced leaf water loss and were more sensitive to drought stress than wild-type plants. By contrast, transgenic Arabidopsis plants overexpressing NFYA5 displayed reduced leaf water loss and were more resistant to drought stress than the wild type. Microarray analysis indicated that NFYA5 is crucial for the expression of a number of drought stress-responsive genes. Thus, NFYA5 is important for drought resistance, and its induction by drought stress occurs at both the transcriptional and posttranscriptional levels.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Although effects of weather changes on human health have been widely reported, there is limited information regarding effects on pregnant women in developing countries.
We investigated the ...association between maternal exposure to ambient temperature and the risk of preterm birth (< 37 weeks of gestation) in Guangzhou, China.
We used a Cox proportional hazards model to estimate associations between preterm birth and average temperature during each week of gestation, with weekly temperature modeled as a time-varying exposure during four time windows: 1 week (the last week of the pregnancy), 4 weeks (the last 4 weeks of the pregnancy), late pregnancy (gestational week 20 onward), and the entire pregnancy. Information on singleton vaginal birth between 2001 and 2011 was collected. Daily meteorological data during the same period were obtained from the Guangzhou Meteorological Bureau.
A total of 838,146 singleton vaginal births were included, among which 47,209 (5.6%) were preterm births. High mean temperatures during the 4 weeks, late pregnancy, and the entire pregnancy time windows were associated with an increased risk of preterm birth. Compared with the median temperature (24.4°C), weekly exposures during the last 4 weeks of the pregnancy to extreme cold (7.6°C, the 1st percentile) and extreme heat (31.9°C, the 99th percentile) were associated with 17.9% (95% CI: 10.2, 26.2%) and 10.0% (95% CI: 2.9, 17.6%) increased risks of preterm birth, respectively. The association between extreme heat and preterm birth was stronger for preterm births during weeks 20-31 and 32-34 than those during weeks 35-36.
These findings might have important implications in preventing preterm birth in Guangzhou as well as other areas with similar weather conditions.
He JR, Liu Y, Xia XY, Ma WJ, Lin HL, Kan HD, Lu JH, Feng Q, Mo WJ, Wang P, Xia HM, Qiu X, Muglia LJ. 2016. Ambient temperature and the risk of preterm birth in Guangzhou, China (2001-2011). Environ Health Perspect 124:1100-1106; http://dx.doi.org/10.1289/ehp.1509778.
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CEKLJ, DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
The coronavirus disease 2019 (COVID-19) has been spreading worldwide. Severe cases quickly progressed with unfavorable outcomes. We aim to investigate the clinical features of COVID-19 and identify ...the risk factors associated with its progression. Data of confirmed SARS-CoV-2-infected patients and healthy participants were collected. Thirty-seven healthy people and 79 confirmed patients, which include 48 severe patients and 31 mild patients, were recruited. COVID-19 patients presented with dysregulated immune response (decreased T, B, and NK cells and increased inflammatory cytokines). Also, they were found to have increased levels of white blood cell, neutrophil count, and D-dimer in severe cases. Moreover, lymphocyte, CD4
T cell, CD8
T cell, NK cell, and B cell counts were lower in the severe group. Multivariate logistic regression analysis showed that CD4
cell count, neutrophil-to-lymphocyte ratio (NLR) and D-dimer were risk factors for severe cases. Both CT score and clinical pulmonary infection score (CPIS) were associated with disease severity. The receiver operating characteristic (ROC) curve analysis has shown that all these parameters and scores had quite a high predictive value. Immune dysfunction plays critical roles in disease progression. Early and constant surveillance of complete blood cell count, T lymphocyte subsets, coagulation function, CT scan and CPIS was recommended for early screening of severe cases.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Pursuant to the Paris Agreement, China committed itself to peak its carbon emissions by around 2030 and to increase the non-fossil share of primary energy to 20% at the same time. The government has ...supported the international agreement by setting and strengthening the domestic policy targets for an earlier peak and faster reduction, aiming to contain the average global temperature increase to well below 2 °C. We develop a Kaya Inequality method to assess the time of peak and pace of reduction of China's energy-related CO2 emissions based on the national energy policy targets for 2030. We find that, despite the minor fluctuations, the current plateau essentially represents the peak emissions and should enter a phase of steady decline by around 2025, given current trends in energy consumption and decarbonization. Such developments would be consistent with the strengthened national policy target to achieve 50% of renewable power generation by 2030. However, the basic policy targets – a 20% share of non-fossil energy and 6 Gtce in total energy consumption by 2030 – would be insufficient to peak carbon emissions by around 2030. The synergy and interplay between domestic policy target setting and international climate commitments shed light on the need to elevate national climate ambitions under the Paris Agreement and beyond.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Trimethylated histone H3 lysine 27 (H3K27me3) is a repressive histone marker that regulates a variety of developmental processes, including those that determine flowering time. However, relatively ...little is known about the mechanism of how H3K27me3 is recognized to regulate transcription. Here, we identified BAH domain‐containing transcriptional regulator 1 (BDT1) as an H3K27me3 reader. BDT1 is responsible for preventing flowering by suppressing the expression of flowering genes. Mutation of the H3K27me3 recognition sites in the BAH domain disrupted the binding of BDT1 to H3K27me3, leading to de‐repression of H3K27me3‐enriched flowering genes and an early‐flowering phenotype. We also found that BDT1 interacts with a family of PHD finger‐containing proteins, which we named PHD1–6, and with CPL2, a Pol II carboxyl terminal domain (CTD) phosphatase responsible for transcriptional repression. Pull‐down assays showed that the PHD finger‐containing proteins can enhance the binding of BDT1 to the H3K27me3 peptide. Mutations in all of the PHD genes caused increased expression of flowering genes and an early‐flowering phenotype. This study suggests that the binding of BDT1 to the H3K27me3 peptide, which is enhanced by PHD proteins, is critical for preventing early flowering.
BAH DOMAIN‐CONTAINING TRANSCRIPTIONAL REGULATOR 1 (BDT1) functions as a histone H3K27me3 reader. A group of PHD finger‐containing proteins interact with BDT1 and enhance BDT1 binding to H3K27me3. BDT1 and the PHD finger‐containing proteins associate with H3K27me3‐enriched flowering genes and repress their transcription, thereby preventing early flowering.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Blending with biodegradable poly (butylene succinate) (PBS) is an effective way for improving the performance of PLA. However, the property of the blends is not significantly improved due to poor ...compatibility between the two polymers. Herein, we propose a simple method to prepare biodegradable PLA/PBS blends successfully by UV-induced reactive extrusion. Multifunctional monomer trimethylolpropane tri-acrylate (TMPTA) is used as chain extender to react with PLA and PBS to generate graft copolymers at the PLA/PBS interface. Addition of glycidyl methacrylate (GMA) could further promote the graft reaction, thus increase the compatibility and the mechanical properties of the blends. The occurrence of the long chain branched reaction between the PLA and PBS is evidenced by the rheological results and Fourier-transform infrared spectroscopy analysis. Appropriate amount of GMA reduces the size of dispersed PBS phase and enhances the interfacial strength. The crystallization of PLA is effectively improved, as evidenced by the increased cool crystallization peak and apparent enhancement crystallinity. Ultimately, PLA/PBS blends compatibilized with GMA/TMPTA exhibit a remarkable improvement in elongation at break of 341%, notched impact strength and a preferable maintenance of 50 MPa in tensile strength.
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•The synergistic effect of GMA and TMPTA plays a good role in compatibilization.•Chain extension and crystallization of PLA/PBS blends are realized simultaneously.•This strategy can maintain good mechanical properties of composites.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Autophagy is a lysosomal degradation process known as autophagic flux, involving the engulfment of damaged proteins and organelles by double-membrane autophagosomes. It comprises microautophagy, ...chaperone-mediated autophagy (CMA), and macroautophagy. Macroautophagy consists of three stages: induction, autophagosome formation, and autolysosome formation. Atg8-family proteins are valuable for tracking autophagic structures and have been widely utilized for monitoring autophagy. The conversion of LC3 to its lipidated form, LC3-II, served as an indicator of autophagy. Autophagy is implicated in human pathophysiology, such as neurodegeneration, cancer, and immune disorders. Moreover, autophagy impacts urological diseases, such as interstitial cystitis /bladder pain syndrome (IC/BPS), ketamine-induced ulcerative cystitis (KIC), chemotherapy-induced cystitis (CIC), radiation cystitis (RC), erectile dysfunction (ED), bladder outlet obstruction (BOO), prostate cancer, bladder cancer, renal cancer, testicular cancer, and penile cancer. Autophagy plays a dual role in the management of urologic diseases, and the identification of potential biomarkers associated with autophagy is a crucial step towards a deeper understanding of its role in these diseases. Methods for monitoring autophagy include TEM, Western blot, immunofluorescence, flow cytometry, and genetic tools. Autophagosome and autolysosome structures are discerned via TEM. Western blot, immunofluorescence, northern blot, and RT-PCR assess protein/mRNA levels. Luciferase assay tracks flux; GFP-LC3 transgenic mice aid study. Knockdown methods (miRNA and RNAi) offer insights. This article extensively examines autophagy’s molecular mechanism, pharmacological regulation, and therapeutic application involvement in urological diseases.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK