...we combined the opinions of frontline epidemic control experts and reviewed the evidence in relevant literature. Two members of the evidence assessment team performed independent computer searches ...of English databases (PubMed, Ovid, Embase), Chinese databases (Chinese Biological Medical Literature database, China National Knowledge Infrastructure, Chinese Medical Journal Database), and relevant online website bulletins on COVID-19 (the World Health Organization, Elsevier, the Lancet, the New England Journal of Medicine, and the Journal of the American Medical Association, 2019 Novel Coronavirus Resource (2019nCoVR), and the Chinese Medical Journal Network). The search terms included the English terms and their Chinese equivalents: “novel coronavirus pneumonia,” “NCP,” “severe acute respiratory syndrome,” “SARS,” “Middle East Respiratory Syndrome,” “MERS,” “influenza,” “psychological therapy,” “guideline,” “statement,” “recommendation,” “randomized controlled trial,” and other rehabilitation-related English search terms and their Chinese equivalents included “respiratory rehabilitation,” “pulmonary rehabilitation,” “physiotherapy,” “physical therapy,” and “occupational therapy.” 11 Recommendations Intervention timing for respiratory rehabilitation in moderately ill patients Due to the limited understanding of the pathophysiological mechanisms of COVID-19, current clinical observations found that around 3% to 5% of moderately ill patients develop severe or even critical disease after 7 to 14 days of infection. ...the exercise intensity should not be too high as its objective is to maintain the existing physical status.
Mutant ZP1 in familial infertility Huang, Hua-Lin; Lv, Chao; Zhao, Ying-Chun ...
The New England journal of medicine,
03/2014, Letnik:
370, Številka:
13
Journal Article
Recenzirano
Odprti dostop
The human zona pellucida is composed of four glycoproteins (ZP1, ZP2, ZP3, and ZP4) and has an important role in reproduction. Here we describe a form of infertility with an autosomal recessive mode ...of inheritance, characterized by abnormal eggs that lack a zona pellucida. We identified a homozygous frameshift mutation in ZP1 in six family members. In vitro studies showed that defective ZP1 proteins and normal ZP3 proteins colocalized throughout the cells and were not expressed at the cell surface, suggesting that the aberrant ZP1 results in the sequestration of ZP3 in the cytoplasm, thereby preventing the formation of the zona pellucida around the oocyte.
Rationally optimizing the photoluminescence performance via accurate structural modulation is one of most important and challenging issues for hybrid halides. Herein, a viable crystal dimensional ...reduction strategy is proposed to reasonably enhance the photoluminescence quantum yield (PLQY) of hybrid antimony halide. Specifically, a synthetic technique is developed and new 1D DMPZSbCl5 ∙ H2O (DP‐SbCl5) is sliced to 0D DMPZ2SbCl6 ∙ Cl ∙ (H2O)2 (DP‐SbCl6) with crystal dimensional reduction from infinite SbCl52− chain to discrete SbCl63− octahedron. Comparing with nonluminescent 1D DP‐SbCl5, 0D DP‐SbCl6 displays highly efficient broadband yellow light emission with enhanced PLQY up to 75.94%. First‐principles calculation demonstrates that 0D DP‐SbCl6 features more flat and narrow band structure, which promotes the photoelectron localization and increases the quantum confinement, and finally boosts the luminescence efficiency. Together highly efficient and ultra‐stable luminescence performance enable DP‐SbCl6 as excellent down‐conversion broadband yellow phosphor to successfully fabricate white light emitting diodes with a high color rendering index of 92. This work provides a novel structural modulation strategy of crystal dimensional reduction to rationally optimize the PL performance of hybrid metal halides.
With controllable structural evolution from 1D to 0D hybrid antimony halides, the photoluminescence quantum yield (PLQY) realizes a notable enhancement from <1% to 75.94% in yellow spectral region benefitting from more localized photoelectrons and increased quantum confinement. This work provides a structural platform to verify the feasibility of crystal dimensionality reduction strategy to rationally improve the PLQY of metal halides.
Covering: up to 2020As a main bioactive component of the Chinese, Indian, and American Podophyllum species, the herbal medicine, podophyllotoxin (PTOX) exhibits broad spectrum pharmacological ...activity, such as superior antitumor activity and against multiple viruses. PTOX derivatives (PTOXs) could arrest the cell cycle, block the transitorily generated DNA/RNA breaks, and blunt the growth-stimulation by targeting topoisomerase II, tubulin, or insulin-like growth factor 1 receptor. Since 1983, etoposide (VP-16) is being used in frontline cancer therapy against various cancer types, such as small cell lung cancer and testicular cancer. Surprisingly, VP-16 (ClinicalTrials NTC04356690) was also redeveloped to treat the cytokine storm in coronavirus disease 2019 (COVID-19) in phase II in April 2020. The treatment aims at dampening the cytokine storm and is based on etoposide in the case of central nervous system. However, the initial version of PTOX was far from perfect. Almost all podophyllotoxin derivatives, including the FDA-approved drugs VP-16 and teniposide, were seriously limited in clinical therapy due to systemic toxicity, drug resistance, and low bioavailability. To meet this challenge, scientists have devoted continuous efforts to discover new candidate drugs and have developed drug strategies. This review focuses on the current clinical treatment of PTOXs and the prospective analysis for improving druggability in the rational design of new generation PTOX-derived drugs.
•UV radiation increased litter decomposition in hyper-arid regions.•Photodegradation effects were not strongest at the driest region.•Photodegradation effects on N loss dynamic depended on litter ...quality.•Lignin loss did not account for the increased mass loss under UV radiation.
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Photodegradation due to litter exposure to solar UV radiation is presumed to contribute to the surprisingly fast decomposition in some arid and semi-arid regions; however, few studies have directly examined photodegradation effects in hyper-arid regions (annual precipitation <150mm) and its dependence on precipitation. Three litters with different initial qualities (low vs high C:N) were decomposed under full spectrum sunlight (UV radiation) and UV filtering from solar radiation at three sites with contrasting precipitation amounts (144mm, 76mm and 16mm) for 2.5years. UV radiation increased mass loss and litter decomposition rates by 23–70%. UV photodegradation effects (UVE) on litter decomposition rate differed among experimental sites, with significantly stronger effects in less arid sites (144mm and 76mm) than more arid site (16mm). High-quality litter (low C:N ratio) showed the fastest decomposition rate, and UVE was also affected by litter quality, but no consistent trend was observed. Litter N loss was greatest in full sunlight and the linear relationships between C and N contents was not changed by UV filtering over time. UV radiation increased C loss of all fractions, and hemicellulose and cell solubles showed significant contributions to litter mass loss. Our findings suggest that UV photodegradation can increase mass loss and nutrient release by the positive priming effects on microbial decomposition in hyper-arid regions, although UVE differed among three sites with contrasting precipitation amounts.
Imbalanced Th17/Treg ratio is implicated in the pathogenesis of aplastic anemia. Studies have indicated that bone marrow-derived mesenchymal stem cells-derived exosomes (BMSC-Exo) could correct ...imbalanced Th17/Treg in aplastic anemia, but the mechanism remains not fully understand. This study was designed to investigate whether BMSC-Exo regulates the Th17/Treg balance in aplastic anemia by transferring miR-23a-3p. Here, miR-23a-3p inhibitor was utilized to knockdown the expression of miR-23a-3p in BMSC-Exo. A co-culture system of CD4
+
T cells from aplastic anemia patients and BMSC-Exo was used to explore the effects of BMSC-Exo on the Th17/Treg balance and the underlying mechanism in aplastic anemia. The patients with aplastic anemia exhibited Th17/Treg imbalance favoring the Th17 cells. BMSC-Exo could balance the percentage of Th17 and Treg cells in aplastic anemia, but the effects of BMSC-Exo can be eliminated when miR-23a-3p expression was silenced in BMSCs. IL-6 was a direct target of miR-23a-3p. IL-6 overexpression could abrogate BMSC-Exo-induced balance in Th17/Treg ratio. Overall, BMSC-Exo could balance Th17/Treg ratio in aplastic anemia via suppressing IL-6 expression by transferring miR-23a-3p at least in part. These data indicated miR-23a-3p may be a potential target for the treatment of aplastic anemia. Our study may provide a new idea for the therapy of the disease.
Several studies have examined the functions of nucleic acids in small extracellular vesicles (sEVs). However, much less is known about the protein cargos of sEVs and their functions in recipient ...cells. This study demonstrates the presence of lysine‐specific demethylase 1 (LSD1), which is the first identified histone demethylase, in the culture medium of gastric cancer cells. We show that sEVs derived from gastric cancer cells and the plasma of patients with gastric cancer harbor LSD1. The shuttling of LSD1‐containing sEVs from donor cells to recipient gastric cancer cells promotes cancer cell stemness by positively regulating the expression of Nanog, OCT4, SOX2, and CD44. Additionally, sEV‐delivered LSD1 suppresses oxaliplatin response of recipient cells in vitro and in vivo, whereas LSD1‐depleted sEVs do not. Taken together, we demonstrate that LSD1‐loaded sEVs can promote stemness and chemoresistance to oxaliplatin. These findings suggest that the LSD1 content of sEV could serve as a biomarker to predict oxaliplatin response in gastric cancer patients.
Synopsis
Lysine specific demethylase 1 is not only a nuclear protein but is also secreted. Gastric cancer cells release sEVs that contain LSD1, thereby promoting cancer cell stemness and oxaliplatin resistance.
LSD1 is a component of small extracellular vesicles (sEVs) from gastric cancer cells and gastric cancer patient plasma.
LSD1‐containing sEVs increase the expression of Nanog, OCT4, SOX2 and CD44, and promote oxaliplatin resistance.
sEVs‐delivered LSD1 may serve as a potential biomarker to predict oxaliplatin response in the clinic.
Lysine specific demethylase 1 is not only a nuclear protein but is also secreted. Gastric cancer cells release sEVs that contain LSD1, thereby promoting cancer cell stemness and oxaliplatin resistance.
Alzheimer's disease (AD) is a neurodegenerative disorder with cognitive impairment and abnormal mental behaviour. There is currently no effective cure. The development of early diagnostic markers and ...the mining of potential therapeutic targets are one of the important strategies. This study aimed to explore potential biomarkers or therapeutic targets related to AD in the hippocampus and prefrontal cortex, two brain regions highly related to AD. Differentially expressed genes and miRNAs between AD patients and healthy controls were obtained from the Gene Expression Omnibus database. The mRNA‐miRNA network was constructed and key genes involved in AD were screened out by protein–protein interaction analysis, and were subsequently verified by independent datasets and qPCR in an AD mouse model. Our findings showed that six hub genes including CALN1, TRPM7, ATR, SOCS3, MOB3A and OGDH were believed to be involved in the pathogenesis of AD. Western blot analysis further determined that CALN1, ATR and OGDH were the possible biomarkers and therapeutic targets for AD. In addition, 6 possible miRNAs biomarkers have also been verified by qPCR on AD animal models. Our findings may benefit clinical diagnosis and early prevention of AD.
Viral diarrhea is one of the leading causes of morbidity and mortality in children. This study was conducted to disclose the etiological cause and epidemiological features of viral diarrhea among ...children in China. From 2009 to 2021, active surveillance was performed on pediatric patients with acute diarrhea and tested for five enteric viruses. Positive detection was determined in 65.56% (3325/5072) patients and an age‐specific infection pattern was observed. A significantly higher positive rate was observed in 12–23‐month‐old children for rotavirus (47.46%) and adenovirus (7.06%), while a significantly higher positive rate was observed for norovirus (37.62%) in 6–11‐month‐old patients, and for astrovirus (11.60%) and sapovirus (10.79%) in 24–47‐month‐old patients. A higher positive rate of rotavirus in girls and norovirus in boys was observed only among 6–11 months of patients. We also observed more norovirus among patients from rural areas in the 0–5‐ and 36–47‐month groups and more rotavirus among those from rural areas in the 12–23‐month group. Diarrhea severity was greater for rotavirus in the 6–23‐month group and norovirus in the 6–11‐month group. Coinfections were observed in 29.26% (973/3325) of positive patients, and were most frequently observed between rotavirus and others (89.31%). Our findings could help the prediction, prevention, and potential therapeutic approaches to viral diarrhea in children.
Mitochondrial dysfunction is an early feature of Alzheimer's disease (AD). Accumulated damaged mitochondria, which are associated with impaired mitophagy, contribute to neurodegeneration in AD. We ...show levels of Disrupted‐in‐schizophrenia‐1 (DISC1), which is genetically associated with psychiatric disorders and AD, decrease in the brains of AD patients and transgenic model mice and in Aβ‐treated cultured cells. Disrupted‐in‐schizophrenia‐1 contains a canonical LC3‐interacting region (LIR) motif (210FSFI213), through which DISC1 directly binds to LC3‐I/II. Overexpression of DISC1 enhances mitophagy through its binding to LC3, whereas knocking‐down of DISC1 blocks Aβ‐induced mitophagy. We further observe overexpression of DISC1, but not its mutant (muFSFI) which abolishes the interaction of DISC1 with LC3, rescues Aβ‐induced mitochondrial dysfunction, loss of spines, suppressed long‐term potentiation (LTP). Overexpression of DISC1 via adeno‐associated virus (serotype 8, AAV8) in the hippocampus of 8‐month‐old APP/PS1 transgenic mice for 4 months rescues cognitive deficits, synaptic loss, and Aβ plaque accumulation, in a way dependent on the interaction of DISC1 with LC3. These results indicate that DISC1 is a novel mitophagy receptor, which protects synaptic plasticity from Aβ accumulation‐induced toxicity through promoting mitophagy.
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