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Severe acute respiratory syndrome coronavirus 2 was isolated from feces of a patient in China with coronavirus disease who died. Confirmation of infectious virus in feces affirms the potential for fecal-oral or fecal-respiratory transmission and warrants further study.

SARS-CoV-2 caused a major outbreak of severe pneumonia (COVID-19) in humans. Viral RNA was detected in multiple organs in COVID-19 patients. However, infectious SARS-CoV-2 was only isolated from respiratory specimens. Here, infectious SARS-CoV-2 was successfully isolated from urine of a COVID-19 patient. The virus isolated could infect new susceptible cells and was recognized by its' own patient sera. Appropriate precautions should be taken to avoid transmission from urine.

Mitophagy alleviates neuronal damage after cerebral ischemia by selectively removing dysfunctional mitochondria. Phosphatase and tensin homolog (PTEN) induced putative kinase 1 (PINK1)/Parkin-mediated mitophagy is the most well-known type of mitophagy. However, little is known about the role of PINK1/Parkin-mediated mitophagy in ischemic tolerance induced by hypoxic postconditioning (HPC) with 8% O 2 against transient global cerebral ischemia (tGCI). Hence, we aimed to test the hypothesis that HPC-mediated PINK1/Parkin-induced mitochondrial ubiquitination and promotes mitophagy, thus exerting neuroprotection in the hippocampal CA1 subregion against tGCI. We found that mitochondrial clearance was disturbed at the late phase of reperfusion after tGCI, which was reversed by HPC, as evidenced by the reduction of the translocase of outer mitochondrial membrane 20 homologs (TOMM20), translocase of inner mitochondrial membrane 23 (TIMM23) and heat shock protein 60 (HSP60) in CA1 after HPC. In addition, HPC further increased the ratio of LC3II/I in mitochondrial fraction and promoted the formation of mitophagosomes in CA1 neurons after tGCI. The administration of lysosome inhibitor chloroquine (CQ) intraperitoneally or mitophagy inhibitor (Mdivi-1) intracerebroventricularly abrogated HPC-induced mitochondrial turnover and neuroprotection in CA1 after tGCI. We also found that HPC activated PINK1/Parkin pathway after tGCI, as shown by the augment of mitochondrial PINK1 and Parkin and the promotion of mitochondrial ubiquitination in CA1. In addition, PINK1 or Parkin knockdown with small-interfering RNA (siRNA) suppressed the activation of PINK1/Parkin pathway and hampered mitochondrial clearance and attenuated neuroprotection induced by HPC, whereas PINK1 overexpression promoted PINK1/Parkin-mediated mitophagy and ameliorated neuronal damage in CA1 after tGCI. Taken together, the new finding in this study is that HPC-induced neuroprotection against tGCI through promoting mitophagy mediated by PINK1/Parkin-dependent pathway.

Wetlands, as a regulator of water cycle and balance, play a key role in preventing flood and drought disasters and protecting biodiversity. The Yellow River Basin is an important ecological barrier and economic zone in our country. By predicting the distribution of wetland landscape and evaluating its evolutionary characteristics, strategies for wetland conservation and utilization in the Yellow River Basin can be formulated. Future land use simulation model can not only simulate the change of multiple land use types, but also reflect the uncertainty of real land use change. In this study, the model was improved and used to predict future wetland changes in the Yellow River Basin. Using the wetland distribution data in 2000 as the initial data, and the wetland distribution data in 2015 as the validation data, setting the parameters according to the land use data of the Yellow River Basin from 1980 to 2000 and the wetland type transfer matrix, after verifying the applicability of the model, the spatial distribution pattern of wetlands in the Yellow River Basin in 2030 was simulated. This research shows that the cost matrix setting method based on the wetland transfer matrix can effectively avoid the errors caused by subjective judgment assignment. By 2030, the wetland distribution in the Yellow River Basin will remain stable, with marshes, paddy fields, and beaches as the main types, similar to 2015. Of all the regions in the Yellow River Basin, Zhengzhou had the highest rate of wetland loss, down 31.94%. On the contrary, Sanmenxia had the highest growth rate of 24.44%.

The interplay between lipid droplets (LDs) and endosomes remains unknown. Here, we screen and synthesize AP1-coumarin, an LD-specific probe, by conjugating a fluorescent dye coumarin to a triazine compound AP1. AP1-coumarin labels all stages of LDs in live cells and markedly induces the accumulation of enlarged RAB5-RAB7 double-positive intermediate endosomes. The AP1-coumarin-labeled LDs contact these intermediate endosomes, with some LDs even being engulfed in them. When LD biogenesis is inhibited, the ability of AP1-coumarin to label LDs is markedly reduced, and the accumulation of enlarged intermediate endosomes is abolished. Moreover, blocking the biogenesis of LDs decreases the number of late endosomes while increasing the number of early endosomes and inhibits the endosomal trafficking of low-density lipoprotein (LDL) and transferrin. Correspondingly, interference with RAB5 or RAB7, either through knockdown or using dominant-negative mutants, inhibits LD catabolism, whereas the expression of a RAB7 constitutively active mutant accelerates LD catabolism. Additionally, CCZ1 knockdown not only induces the accumulation of intermediate endosomes but also inhibits LD catabolism. These results collectively suggest that LDs and endosomes interact and influence each other’s functions, and endosomal trafficking participates in the catabolic process of LDs to maintain lipid homeostasis. Lipid droplets (LDs) and endosomes play crucial roles in cellular processes, yet their interplay is poorly understood. Here, the authors develop an LD-specific probe, AP1-coumarin, and reveal dynamic interactions between LDs and endosomes, regulating lipid homeostasis.

Nucleoli are fundamentally essential sites for ribosome biogenesis in cells and formed by liquid-liquid phase separation (LLPS) for a multilayer condensate structure. How the nucleoli integrity is maintained remains poorly understood. Here, we reveal that METTL3/METTL14, the typical methyltransferase complex catalyzing N6-methyladnosine (m 6 A) on mRNAs maintain nucleoli integrity in human embryonic stem cells (hESCs). METTL3/METTL14 deficiency impairs nucleoli and leads to the complete loss of self-renewal in hESCs. We further show that SUV39H1/H2 protein, the methyltransferases catalyzing H3K9me3 were dramatically elevated in METTL3/METTL14 deficient cells, which causes an accumulation and infiltration of H3K9me3 across the whole nucleolus and impairs the LLPS. Mechanistically, METTL3/METTL14 complex serves as an essential adapter for CRL4 E3 ubiquitin ligase targeting SUV39H1/H2 for polyubiquitination and proteasomal degradation and therefore prevents H3K9me3 accumulation in nucleoli. Together, these findings uncover a previously unknown role of METTL3/METTL14 to maintain nucleoli integrity by facilitating SUV39H1/H2 degradation in human cells. Nucleoli are essential cellular sites for ribosome biogenesis that are formed by liquid-liquid phase separation. Here the authors show that METTL3/METTL14 maintain nucleoli integrity through mediating SUV39H1/2 degradation in human embryonic stem cells.

The class III PI3-kinase (PIK3C3) is an enzyme responsible for the generation of phosphatidylinositol 3-phosphate (PI3P), a critical component of vesicular membrane. Here, we report that PIK3C3 deficiency in zebrafish results in intestinal injury and inflammation. In pik3c3 mutants, gut tube forms but fails to be maintained. Gene expression analysis reveals that barrier-function-related inflammatory bowel disease (IBD) susceptibility genes ( e-cadherin , hnf4a , ttc7a ) are suppressed, while inflammatory response genes are stimulated in the mutants. Histological analysis shows neutrophil infiltration into mutant intestinal epithelium and the clearance of gut microbiota. Yet, gut microorganisms appear dispensable as mutants cultured under germ-free condition have similar intestinal defects. Mechanistically, we show that PIK3C3 deficiency suppresses the formation of PI3P and disrupts the polarized distribution of cell-junction proteins in intestinal epithelial cells. These results not only reveal a role of PIK3C3 in gut homeostasis, but also provide a zebrafish IBD model. The functions of the class III PI3-kinase (PIK3C3) in gut homeostasis and innate immunity are poorly understood. Here the authors show that PIK3C3-deficient zebrafishes develop intestinal injury and inflammation due to mislocalization of cell junction proteins.

Ribosome biogenesis plays a pivotal role in maintaining stem cell homeostasis, yet the precise regulatory mechanisms governing this process in mouse embryonic stem cells (mESCs) remain largely unknown. In this investigation, we ascertain that DEAD-box RNA helicase 10 (DDX10) is indispensable for upholding cellular homeostasis and the viability of mESCs. Positioned predominantly at the nucleolar dense fibrillar component (DFC) and granular component (GC), DDX10 predominantly binds to 45S ribosomal RNA (rRNA) and orchestrates ribosome biogenesis. Degradation of DDX10 prevents the release of U3 snoRNA from pre-rRNA, leading to perturbed pre-rRNA processing and compromised maturation of the 18S rRNA, thereby disrupting the biogenesis of the small ribosomal subunit. Moreover, DDX10 participates in the process of liquid-liquid phase separation (LLPS), which is necessary for efficient ribosome biogenesis. Notably, the NUP98-DDX10 fusion associated with acute myelocytic leukemia (AML) alters the cellular localization of DDX10 and results in loss of ability to regulate pre-rRNA processing. Collectively, this study reveals the critical role of DDX10 as a pivotal regulator of ribosome biogenesis in mESCs. Ribosome biogenesis is crucial for maintaining stem cell homeostasis. Here, authors reveal that DDX10 plays a critical role in ribosome biogenesis by regulating 18S rRNA maturation, which is vital for the proliferation and maintenance of mESCs.

Selecting road networks in cartographic generalization has consistently posed formidable challenges, driving research toward the application of intelligent models. Despite previous efforts, the accuracy and connectivity preservation in these studies, particularly when dealing with road types of similar sample sizes, still warrant improvement. To address these shortcomings, we introduce a Heterogeneous Graph Attention Network (HAN) for road selection, where the feature masking method is initially utilized to assess the significance of road features. Concentrating on the most relevant features, two meta-paths are introduced within the HAN framework: one for aggregating features of the same road type within the first-order neighborhood, emphasizing local connectivity, and another for extending this aggregation to the second-order neighborhood, capturing a broader spatial context. For a comprehensive evaluation, we use a set of metrics considering both quantitative and qualitative aspects of the road network. On road types with similar sample sizes, the HAN model outperforms other models in both transductive and inductive tasks. Its accuracy (ACC) is higher by 1.62% and 0.67%, and its F1-score is higher by 1.43% and 0.81%, respectively. Additionally, it enhances the overall connectivity of the selected network. In summary, our HAN-based method provides an advanced solution for road network selection, surpassing previous approaches in terms of accuracy and connectivity preservation.

Celastrol, an active ingredient derived from , has shown therapeutic potential for various kidney renal diseases. The kidney protective activity of celastrol is mainly exerted through anti-inflammatory, and antioxidant effects. However, celastrol causes dose-dependent kidney toxicity, which results in increased risks of mortality among patients. This study aimed to develop a kidney organoid-based prediction system to assess the safety and efficacy of celastrol in reducing cisplatin-induced nephrotoxicity. We investigated the ability of celastrol to reduce cisplatin-induced nephrotoxicity using kidney organoids. Kidney organoids were cultured and characterized, exhibiting renal tubular and glomerular structures and expressing specific kidney markers such as NPHS1, CD31, LTL, and SLC12A1. Data were obtained from experiments in which kidney organoids were exposed to therapeutically relevant concentrations or a toxic dosing profile of cisplatin and celastrol, to assess their impact on cell viability using flow cytometry and Acridine Orange/Propidium Iodide (AO/PI) staining. In addition, RNA-seq analyses were performed to determine the mechanisms of celastrol function in the kidney. Kidney organoids exposed to 50 µM cisplatin showed significantly increased cell death (only 0.37% cells with normal cell structure), whereas celastrol under 5 µM (56% cells with normal cell structure) showed significantly less nephrotoxicity than cisplatin. The protective effects of celastrol against cisplatin-induced nephrotoxicity were further investigated by treating the organoids with both compounds. The results demonstrated that 2 µM celastrol reduced cisplatin-induced nephrotoxicity by downregulating SNORD3A and HIST1H3A gene levels. This study highlights the potential of celastrol as a protective compound against cisplatin-induced kidney damage and emphasizes the importance of using advanced models, such as iPSC-derived kidney organoids, to predict therapeutic effect and nephrotoxic concentrations of novel drugs.