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Aging is an inevitable process influenced by genetics, lifestyles, and environments. With the rapid social and economic development in recent decades, the proportion of the elderly has increased rapidly worldwide, and many aging-related diseases have shown an upward trend, including nervous system diseases, cardiovascular diseases, metabolic diseases, and cancer. The rising burden of aging-related diseases has become an urgent global health challenge and requires immediate attention and solutions. Natural products have been used for a long time to treat various human diseases. The primary cellular pathways that mediate the longevity-extending effects of natural products involve nutrient-sensing pathways. Among them, the sirtuin, AMP-activated protein kinase, mammalian target of rapamycin, p53, and insulin/insulin-like growth factor-1 signaling pathways are most widely studied. Several studies have reviewed the effects of individual natural compounds on aging and aging-related diseases along with the underlying mechanisms. Natural products from food sources, such as polyphenols, saponins, alkaloids, and polysaccharides, are classified as antiaging compounds that promote health and prolong life via various mechanisms. In this article, we have reviewed several recently identified natural products with potential antiaging properties and have highlighted their cellular and molecular mechanisms. The discovery and use of dietary supplements and natural products that can prevent and treat multiple aging-related diseases in humans will be beneficial. Thus, this review provides theoretical background for existing dietary supplements and natural products as potential antiaging agents.

O3 poses a significant threat to human health and the ecological environment. In recent years, O3 pollution has become increasingly serious, making it difficult to accurately control O3 precursor emissions. Satellite indicator methods, such as the FNR (formaldehyde-to-nitrogen dioxide ratio (HCHO/NO2 ratio)), provide an effective way to identify ozone pollution control areas on a large geographical scale due to their simple acquisition of datasets. This can help determine the primary factors contributing to O3 pollution and assist in managing it. Based on TROPOMI data from May 2018 to December 2022, combined with ground-based monitoring data from the China National Environmental Monitoring Centre, we explored the uncertainty associated with using the HCHO/NO2 ratio (FNR) as an indicator in ozone control area determination. We focused on the four representative regions in China: Jing-Jin-Ji-Lu-Yu (JJJLY), Jiang-Zhe-Hu-Wan (JZHW), Chuan-Yu (CY), and South China. By using the statistical curve-fitting method, we found that the FNR thresholds were 3.5–5.1, 2.0–4.0, 2.5–4.2, and 1.7–3.5, respectively. Meanwhile, we analyzed the spatial and temporal characteristics of the HCHO, NO2, and O3 control areas. The HCHO concentrations and NO2 concentrations had obvious cyclical patterns, with higher HCHO column densities occurring in summer and higher NO2 concentrations in winter. These high values always appeared in areas with dense population activities and well-developed economies. The distribution characteristics of the ozone control areas indicated that during O3 pollution periods, the urban areas with industrial activities and high population densities were primarily controlled by VOCs, and the suburban areas gradually shifted from VOC-limited regimes to transitional regimes and eventually reverted back to VOC-limited regimes. In contrast, the rural and other remote areas with relatively less development were mainly controlled by NOx. The FNR also exhibited periodic variations, with higher values mostly appearing in summer and lower values appearing in winter. This study identifies the main factors contributing to O3 pollution in different regions of China and can serve as a valuable reference for O3 pollution control.

Malus sieversii (Ledeb.) M.Roem. is the ancestor of cultivated apples, and is an excellent germplasm resource with high resistance to cold. Artificial refrigerators were used to simulate the low temperature of −3 °C to treat Malus sieversii (Ledeb.) M.Roem. histoculture seedlings. Observations were performed to find the effects of freezing stress on the status of open or closed stomata, photosystems, and detection of metabolomic products in leaves of Malus sieversii (Ledeb.) M.Roem. histoculture seedlings. The percentage of closed stomata in the Malus sieversii (Ledeb.) M.Roem. histoculture seedlings increased, the maximum fluorescence (Fm’) excited by a strong light (saturating pulse) was weakened relative to the real-time fluorescence in its vicinity, and the quantum yield of unregulated energy dissipation was increased in PSII under freezing stress. The metabolites in the leaves of the Malus sieversii (Ledeb. M.Roem.) histoculture seedlings were analyzed by ultra-performance liquid chromatography–tandem mass spectrometry using CK, T12h, T36 h, and HF24h. Results demonstrated that cold stress in the Malus sieversii (Ledeb.) M.Roem. histoculture seedlings led to wilting, leaf stomatal closure, and photosystem damage. There were 1020 metabolites identified as lipids (10.2%), nucleotides and their derivatives (5.2%), phenolic acids (19.12%), flavonoids (24.51%), amino acids and their derivatives (7.75%), alkaloids (5.39%), terpenoids (8.24%), lignans (3.04%), organic acids (5.88%), and tannins (0.88%). There were 110 differential metabolites at CKvsT12h, 113 differential metabolites at CKvsT36h, 87 differential metabolites at T12hvsT36h, 128 differential metabolites at CKvsHF24h, 121 differential metabolites at T12hvsHF24h, and 152 differential metabolites at T36hvsHF24h. The differential metabolites in the leaves of the Malus sieversii (Ledeb.) M.Roem. seedlings grown under low-temperature stress mainly involved glycolysis, amino acid metabolism, lipid metabolism, pyrimidine metabolism, purine metabolism, and secondary metabolite metabolism. The Malus sieversii (Ledeb.) M.Roem. seedlings responded to the freezing stress by coordinating with each other through these metabolic pathways. The metabolic network of the leaves of the Malus sieversii (Ledeb.) M.Roem. histoculture seedlings under low temperature stress was also proposed based on the above pathways to deepen understanding of the response of metabolites of Malus sieversii (Ledeb.) M.Roem. to low-temperature stress and to lay a theoretical foundation for the development and utilization of Malus sieversii (Ledeb.) M.Roem. cultivation resources.

Cell-cell communication is a vital feature involving numerous biological processes. Here, the authors develop SpaTalk, a cell-cell communication inference method using knowledge graph for spatially resolved transcriptomic data, providing valuable insights into spatial intercellular tissue dynamics.

IntroductionAge-related macular degeneration (AMD), an ever-increasing ocular disease, has become one of the leading causes of irreversible blindness. Recent advances in single-cell genomics are improving our understanding of the molecular mechanisms of AMD. However, the pathophysiology of this multifactorial disease is complicated and still an ongoing challenge. To better understand disease pathogenesis and identify effective targets, we conducted an in-depth analysis of the single-cell transcriptome of AMD.MethodsThe cell expression specificity of the gene (CESG) was selected as an index to identify the novel cell markers. A computational framework was designed to explore the cell-specific TF regulatory loops, containing the interaction of gene pattern signatures, transcription factors regulons, and differentially expressed genes.ResultsThree potential novel cell markers were DNASE1L3 for endothelial cells, ABCB5 for melanocytes, and SLC39A12 for RPE cells detected. We observed a notable change in the cell abundance and crosstalk of fibroblasts cells, melanocytes, schwann cells, and T/NK cells between AMD and controls, representing a complex cellular ecosystem in disease status. Finally, we identified six cell type related and three disease-associated ternary loops and elaborated on the robust association between key immune-pathway and AMD.DiscussionIn conclusion, this study facilitates the optimization of screening for AMD-related receptor ligand pathways and proposes to further improve the interpretability of disease associations from single-cell data. It illuminated that immune-related regulation paths could be used as potential diagnostic markers for AMD, and in the future, also as therapeutic targets, providing insights into AMD diagnosis and potential interventions.

ObjectiveWe aimed to evaluate the effects of integrated Chinese and Western medical therapeutic modalities on clinical prognosis in a population with stable angina pectoris (SAP) of coronary heart disease (CHD).MethodsIn a prospective cohort study, 732 patients with SAP of CHD hospitalized in the Integrated Cardiology Unit of the China-Japan Friendship Hospital From October 2020 to October 2021 were included. The patients were divided into integrated treatment and conventional treatment groups according to whether they had been taking Chinese medicine for more than 6 months per year. The occurrence of composite cardiovascular events (CVEs), including cardiac death, non-fatal myocardial infarction, revascularization, stroke, all-cause death, and readmission due to angina attack, heart failure, or malignant arrhythmia, was recorded during follow-up. The effects of different treatment modalities on prognosis were evaluated using univariate and multifactorial logistic regression. Logistic regression models were evaluated using receiver operating characteristic (ROC) curves. In sensitivity analysis, the correlation between treatment modality and outcome events was corrected by rematching the two groups of patients using the propensity score matching (PSM) method.ResultsThe data from 690 patients were included in the analysis, with 327 patients in the integrated treatment group and 363 patients in the conventional treatment group. CVEs occurred in 19 patients (5.8%) in the integrated treatment group and 37 patients (10.2%) in the conventional treatment group. The proportion of outcome events was significantly lower in the combination treatment group than in the conventional treatment group (P = 0.037). Covariate correction by multimodal multifactorial logistic regression revealed a lower risk of CVEs in patients receiving integrated therapy compared with conventional therapy (OR = 0.246, 95% CI = 0.097–0.622, P = 0.003). Moreover, a history of renal insufficiency (OR = 3.991, 95% CI = 1.164–13.684, P = 0.028) and a higher Gensini score (OR = 1.039, 95% CI = 1.028–1.050, P

BackgroundThe real-world experience of dupilumab in Chinese is limited, and the initial loading dose has not yet been deeply explored in patients aged 11 years. Among patients aged 11 years groups, respectively, at week 16. After increasing the loading dose, 69.6% (16/23) of patients aged

BackgroundNumerous research have investigated the predictor role of progesterone (P) level on the human Chorionic Gonadotropin (hCG) trigger day of assisted reproductive technology (ART) outcomes. However, the relationship of progesterone levels on hCG day to clinical pregnancy outcomes in IVF/ICSI cycles for patients with different BMI groups is still elusive. This study aimed to investigate the effects of progesterone elevation on triggering day on clinical pregnancy rate (CPR) of IVF/ICSI cycles in patients with different female BMI.MethodsWe conducted a retrospective cohort study included 6982 normal-weight parents (18.5Kg/m2≤BMI 1.00 ng/ml on triggering day were significantly lower than that (72.4%) of progesterone level

As a potential drug candidate for the treatment of hypertension and complications, it is speculated that the component-based Chinese medicine of Ginkgo biloba leaves (GBCCM) which mainly composed of flavonoid aglycones (FAs) and terpene lactones (TLs) may have different pharmacological effects at different doses or ratios. Taking the normal mice as the study object, metabonomics was conducted by giving different doses of GBCCM. Based on the components of GBCCM absorbed into the blood, the network pharmacological prediction was carried out. By integrating the results of metabonomics and network pharmacology, predict the possible pharmacological effects of GBCCM and conduct experimental verification. It was found that eight of the 19 compounds in GBCCM could be absorbed into the blood. GBCCM mainly affected the signal pathways of unsaturated fatty acid, pyruvate, bile acid, melanin and stem cells. It was speculated that GBCCM might have activities such as lowering blood pressure, regulating stem cell proliferation and melanogenesis. By establishing the models of mushroom tyrosinase, rat bone marrow mesenchymal stem cells (BMSCs) and spontaneously hypertensive rats (SHRs), we found that FAs and TLs showed synergistic effect in hypertension and tyrosinase models, and the optimal ratio was 3:2 (4.4 mg/kg) and 1:1 (0.4 mg/ml), respectively. As effective substances, FAs significantly promoted the proliferation of rat BMSCs on the third and fifth days at the concentration of 0.2 μg/ml (p < 0.05). GBCCM showed a variety of pharmacological effects at different doses and ratios, which provided an important reference for the druggability of GBCCM.

Droplet phase change is important for energy storage and saving technology. The initial profile of the droplet is extremely important for its vaporization or solidification on a horizontal surface. To understand the effect of liquid physical properties on droplet profile, a theoretical model was developed in this study, based on the Young-Laplace equation with gravity effect specially considered. After the model was experimentally validated by comparing the geometric shape of water droplets, it was further used for predicting droplet shapes of other materials, and thus analyzing the influence of different physical properties, such as temperature, pressure, surface wettability, etc. Results show that the results of this model agree well with the experimental data. The maximum and average deviations are less than 4.5% and 1.5%, respectively. For all kinds of droplets on the fixed surfaces, when the temperature increases, the droplet contact radius increases and height decreases. The droplets of nitrogen and carbon dioxide are more sensitive to temperature than ethanol and ethylene glycol droplets. For 20 μL droplets on the surface of contact angle 150°, when the temperature changes from 273.15 K to 293.15 K, the droplet contact radiuses increase by 30.6% for carbon dioxide, 1.2% for ethanol and 0.67% for ethylene glycol, and the droplet heights decrease by 42.9%, 2.5%, 1.1%, respectively. Results of this study are meaningful for predicting the phase change process of droplets on the horizontal surface by controlling their initial profiles.

Due to their fascinating topological structures and application prospects, coordination supramolecular complexes have continuously been studied by scientists. However, the controlled construction and property study of organometallic handcuffs remains a significant and challenging research subject in the area of supramolecular chemistry. Hence, a series of tetranuclear organometallic and heterometallic handcuffs bearing different size and metal types were rationally designed and successfully synthesized by utilizing a quadridentate pyridyl ligand (tetra-(3-pyridylphenyl)ethylene) based on three Cp*Rh (Cp* = η5-C5Me5) fragments bearing specific longitudinal dimensions and conjugated planes. These results were determined with single-crystal X-ray diffraction analysis technology, ESI-MS NMR spectroscopy, etc. Importantly, the photoquenching effect of Cp* groups and the discrepancy of intermolecular π–π stacking interactions between building block and half-sandwich fragments promote markedly different photothermal conversion results. These results will further push the synthesis of topological structures and the development of photothermal conversion materials.

COVID-19 has caused severe threats to lives and damage to property worldwide. The immunopathology of the disease is of particular concern. Currently, researchers have used gene co-expression networks (GCNs) to deepen the study of molecular mechanisms of immune responses to COVID-19. However, most efforts have not fully explored dynamic changes of cell-type-specific molecular networks in the disease process. This study proposes a GCN construction pipeline named single-cell Disease Progression cellular module analysis (scDisProcema), which can trace dynamic changes of immune system response during disease progression using single-cell data. Here, scDisProcema considers changes in cell fate and expression patterns during disease development, identifying gene modules responsible for different immune cells. The hub genes are screened for each module by the specific expression level and the intercellular connectivity of modules. Based on functional items enriched by each gene module, we elucidate the biological processes of different cells involved in disease development and explain the molecular mechanisms underlying the process of cell depletion or proliferation caused by disease. Compared with traditional WGCNA methods, scDisProcema can make more convenient use of the heterogeneity information provided by scRNA-seq data and has great potential in exploring molecular changes during disease progression and organ development.

Semantic segmentation of high-resolution aerial images is a challenging task on account of interclass homogeneity and intraclass heterogeneity of land cover. Recent works have sought to mitigate this issue by exploiting pixelwise global contextual information using self-attention mechanism. However, the existing attention-based methods usually generate inaccurate object boundary segmentation results, as the self-attention model is embedded in high-level features with low resolution due to prohibitively computational complexity. Moreover, existing attention-based models ignore classwise contextual information from intermediate results, which leads to undesirable feature separability. To obtain discriminative feature as well as generate accurate segmentation boundaries, we present a novel segmentation framework, named cascade class-aware enhanced network (CCENet) for high-resolution aerial imagery. The proposed CCENet predicts segmentation results on multiple stages, and the result of the previous stage is used to refine object boundary details for the latter stage. To exploit the class-aware prior information in previous stage, we propose a lightweight class-aware enhanced module (CaEM) to grab the class-aware contextual dependencies. Specifically, CaEM first extracts a set of class representation of the land covers by global class pooling block and then reconstructs enhanced features using class relation measurement, which alleviates the interclass homogeneity and intraclass heterogeneity of ground objects in feature space. Quantitative and qualitative experimental results on three publicly available datasets demonstrate the superiority of our CCENet over other state-of-the-art methods in the items of high labeling accuracy and computation efficiency.

Remote sensing-based change detection (CD) is a critical technique of detecting land surface changes in earth observation. Inspired by recent success of a lightweight CD network– 3M-CDNet, we implemented 9 meaningful modifications to it, for example, the incorporation of MHSA (Multi-Head Self-Attention). This elaborately designed model is termed as 3M-CDNet-V2. Its effectiveness and advantages were demonstrated on three engineering CD datasets, and experimental results indicated that: (1) relative to other state-of-the-art algorithms, the proposed model obtained very competitive or slight better performance on both visual comparison and quantitative metrics evaluation. (2) By applying a novel transfer learning strategy, 3M-CDNet-V2 could perform well on the small dataset. (3) The incorporation of MHSA brings a substantial accuracy improvement while moderately increasing the computational complexity. (4) The late fusion framework and deep supervision contribute most to the performance gain of 3M-CDNet-V2, while the introduction of low-level features to the classifier by skip connection could guide the model to focus on detailed spatial information such as small changes, narrow shaped objects, or accurate boundaries. We hope that our 3M-CDNet-V2 model helps in improving the understanding of network architecture design for CD.

Nanoparticle drug delivery systems have proved anti-tumor effects; however, they are not widely used in tumor therapy due to insufficient ability to target specific sites, multidrug resistance to anti-tumor drugs, and the high toxicity of the drugs. With the development of RNAi technology, nucleic acids have been delivered to target sites to replace or correct defective genes or knock down specific genes. Also, synergistic therapeutic effects can be achieved for combined drug delivery, which is more effective for overcoming multidrug resistance of cancer cells. These combination therapies achieve better therapeutic effects than delivering nucleic acids or chemotherapeutic drugs alone, so the scope of combined drug delivery has also been expanded to three aspects: drug-drug, drug-gene, and gene-gene. This review summarizes the recent advances of nanocarriers to co-delivery agents, including i) the characterization and preparation of nanocarriers, such as lipid-based nanocarriers, polymer nanocarriers, and inorganic delivery carriers; ii) the advantages and disadvantages of synergistic delivery approaches; iii) the effectual delivery cases that are applied in the synergistic delivery systems; and iv) future perspectives in the design of nanoparticle drug delivery systems to co-deliver therapeutic agents.

Abstract The clustered regularly interspaced short palindromic repeats (CRISPR)‐based genetic screening has been demonstrated as a powerful approach for unbiased functional genomics research. Single‐cell CRISPR screening (scCRISPR) techniques, which result from the combination of single‐cell toolkits and CRISPR screening, allow dissecting regulatory networks in complex biological systems at unprecedented resolution. These methods allow cells to be perturbed en masse using a pooled CRISPR library, followed by high‐content phenotyping. This is technically accomplished by annotating cells with sgRNA‐specific barcodes or directly detectable sgRNAs. According to the integration of distinct single‐cell technologies, these methods principally fall into four categories: scCRISPR with RNA‐seq, scCRISPR with ATAC‐seq, scCRISPR with proteome probing, and imaging‐based scCRISPR. scCRISPR has deciphered genotype–phenotype relationships, genetic regulations, tumor biological issues, and neuropathological mechanisms. This review provides insight into the technical breakthrough of scCRISPR by systematically summarizing the advancements of various scCRISPR methodologies and analyzing their merits and limitations. In addition, an application‐oriented approach guide is offered to meet researchers’ individualized demands.

Because of its high prevalence and poor long-term clinical treatment effect, liver disease is regarded as a major public health problem around the world. Among them, viral hepatitis, fatty liver, cirrhosis, non-alcoholic fatty liver disease (NAFLD), and autoimmune liver disease are common causes and inducements of liver injury, and play an important role in the occurrence and development of hepatocellular carcinoma (HCC). Tanshinone IIA (TsIIA) is a fat soluble polyphenol of Salvia miltiorrhiza that is extracted from Salvia miltiorrhiza. Because of its strong biological activity (anti-inflammatory, antioxidant), it is widely used in Asia to treat cardiovascular and liver diseases. In addition, TsIIA has shown significant anti-HCC activity in previous studies. It not only has significant anti proliferation and pro apoptotic properties. It can also play an anti-cancer role by mediating a variety of signal pathways, including phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/rapamycin (mTOR), mitogen-activated protein kinase (MAPK), and nuclear factor kappa-B (NF-κB). This review not only reviews the existing evidence and molecular mechanism of TsIIA’s anti-HCC effect but also reviews the liver-protective effect of TsIIA and its impact on liver fibrosis, NAFLD, and other risk factors for liver cancer. In addition, we also conducted network pharmacological analysis on TsIIA and HCC to further screen and explore the possible targets of TsIIA against hepatocellular carcinoma. It is expected to provide a theoretical basis for the development of anti-HCC-related drugs based on TsIIA.

BackgroundSmartphone addiction (SA) is associated with adverse consequences, especially for freshmen. Evidence indicates that SA is associated with depression, and it is necessary to conduct a longitudinal study to explore the association further.MethodsSA (measured by the Smartphone Addiction Scale-Short Version) and depression (measured by the Zung's Self-Rating Depression Scale) among 1,186 freshmen were surveyed at baseline and a respective 12-month follow-up for each participant. The application of a cross-lagged panel model approach (CLPM) revealed an association between SA and depression after adjusting for demographic variables.ResultsThe CLPM results showed a significant path from baseline SA to follow-up depression (β = 0.08, P < 0.001) and a significant path from baseline depression to follow-up SA (β = 0.08, P < 0.001). Compared with the overall cross-lagged model, the cross-lagged coefficient of the path from baseline SA to follow-up depression increased in the female group (β = 0.10, P = 0.015), and the cross-lagged coefficient of the path from baseline depression to follow-up SA also increased significantly (β = 0.15, P < 0.001). In contrast, the cross-lagged model in the male group showed no predictive effect between SA and depression (P > 0.05).ConclusionsThe current study showed a significant bidirectional association between smartphone addiction and depression among freshmen, but only in the female population.

BackgroundNetherton syndrome is a rare, life-threatening autosomal recessive genetic disorder with no effective treatment yet. Skin barrier dysfunction caused by SPINK5 gene mutations is a hallmark of the disease. Antigen penetration through the defective skin and nonspecific inflammation provide a pro-T helper 2 (Th2) immune microenvironment in the disease. Therefore, Th2 cytokines are considered to be candidate therapeutic targets.ObjectiveTo evaluate the clinical responses of patients with Netherton syndrome to dupilumab, an IL-4Rα antagonist, and identify changes in the Th1/2/17 pathway activity, skin barrier defect protein LEKTI expression after treatment.MethodsFour children with severe Netherton syndrome (aged 2 y to 4 y and 6 m) who were treated with dupilumab from January to June 2022 were evaluated at baseline, and at 4, 8, 12, 16, and 20 weeks after the start of dupilumab administration. Treatment response was assessed using the Eczema Area and Severity Index (EASI), the Numerical Rating Scale (NRS), the Dermatology Life Quality Index (CDLQI), and the Dermatitis Family Impact-questionnaire (DFI). Blood eosinophil counts, serum IgE levels and inflammatory cytokines were measured. The immunotyping of Th1/2/17 cells was performed by flow cytometry and cytokine expressions in T cell subsets were analyzed by single-cell RNA sequencing. In addition, expression of the LEKTI in skin lesions was evaluated by immunohistochemical analysis.ResultsAll four patients experienced clinical improvement, with significantly reduced EASI scores (by 75.0–83.9%) and NRS (by 87.5–90.0%) from baseline to 20 weeks of treatment. Improved quality of life scores were also seen for all patients, as measured by CDLQI and DFI. Serum IgE levels also fell by 75.6–86.9%. The serum Th2 cytokines IL-4, IL-5 and IL-13 were found at low level, with no significant changes during the treatment. However, Th2 cytokines expressed by T cells, especially IL-4, decreased at single-cell level after treatment (P = 0.029). The baseline percentage of Th2 cells (among total CD3+CD4+ T cells) was significantly higher in patients than that in healthy controls (HC) (P < 0.0001); this percentage fell from 8.25% ± 0.75% to 4.02% ± 0.62% after 20 weeks dupilumab treatment. There was no noticeable change in LEKTI protein expression in skin lesions pre- and post-treatment. Two patients reported mild ocular adverse effects, but there were no severe adverse events.ConclusionDupilumab may be an effective and safe treatment option in a subset of pediatric patients with Netherton syndrome, especially in improving itch and the quality of life. These effects were achieved in part by suppression of the Th2-mediated inflammation.

Abstract Background Bone morphogenetic protein 2 (BMP2), growth differentiation factor 8 (GDF8) and their functional receptors are expressed in human ovarian follicles, and these two intrafollicular factors play essential roles in regulating follicle development and luteal function. As BMP antagonists, gremlin1 (GREM1) and gremlin2 (GREM2) suppress BMP signaling through blockage of ligand-receptor binding. However, whether BMP2 regulates the expression of GREM1 and GREM2 in follicular development remains to be determined. Methods In the present study, we investigated the effect of BMP2 on the expression of GREM1 and GREM2 and the underlying mechanisms in human granulosa-lutein (hGL) cells. An established immortalized human granulosa cell line (SVOG) and primary hGL cells were used as study models. The expression of GREM1 and GREM2 were examined following cell incubation with BMP2 at different concentrations and time courses. The TGF-β type I inhibitors (dorsomorphin, DMH-1 and SB431542) and small interfering RNAs targeting ALK2, ALK3, SMAD2/3, SMAD1/5/8 and SMAD4 were used to investigate the involvement of the SMAD-dependent pathway. Results Our results showed that BMP2 significantly increased the expression of GREM2 (but not GREM1) in a dose- and time-dependent manner. Using a dual inhibition approach combining kinase inhibitors and siRNA-mediated knockdown, we found that the BMP2-induced upregulation of GREM2 expression was mediated by the ALK2/3-SMAD1/5-SMAD4 signaling pathway. Moreover, we demonstrated that BMP2 pretreatment significantly attenuated the GDF8-induced phosphorylation of SMAD2 and SMAD3, and this suppressive effect was reversed by knocking down GREM2 expression. Conclusions Our findings provide new insight into the molecular mechanisms by which BMP2 modulates the cellular activity induced by GDF8 through the upregulated expression of their antagonist (GREM2).

Infantile hemangioma (IH) is a benign vascular tumor, characterized by a unique sequence of non-linear growth and spontaneous involution. Some hemangiomas require intensive treatment to avoid functional and aesthetic insufficiency. Although β-adrenergic receptor (β-AR) antagonists have been increasingly used as the first-line treatment since 2008, the IH rebound still exists with uncertain mechanism. Here, we report three cases of abrupt IH deteriorations that are mainly related to β2-AR agonist administration. Potential IH proliferation induced by β2-AR agonists, especially from oral or nebulized approaches, should be recognized more widely by healthcare providers. Additionally, it is necessary to carry out large sample studies to analyze the influence of β2-AR agonist administration on the deterioration of IH.

We calculate the Sivers function of u¯ and d¯ quarks using the overlap representation within the light-cone formalism. The light-cone wave functions of the proton are obtained in terms of the |q¯qB〉 Fock states motivated by the meson-baryon fluctuation model. We consider the final-state interaction at the level of one gluon exchange. In a simplified scenario, the Sivers function of u¯ and d¯ can be expressed as the convolution of the Sivers function of the pion inside the proton and the unpolarized distribution of q¯ inside the pion. The model parameters are fixed by fitting the unpolarized sea quark distributions to the known parameterizations. We present the numerical results for f1⊥u¯/p(x,kT2) and f1⊥d¯/p(x,kT2). The first transverse moment of the sea quark Sivers functions in our model are find to be negative and the magnitude is about 0.004 at most.

Angong Niuhuang Pill (ANP) is a famous traditional Chinese patent medicine and is used for treating ischemic or hemorrhagic stroke for centuries. However, the mechanism of action of ANP in stroke treatment has rarely been reported. With increasing evidence for a mechanistic link between acute ischemic stroke and gut microbiota alterations, this study aimed to determine the mechanism of action of ANP in treating acute ischemic stroke from the perspective of the gut microbiota. A mouse model of acute ischemic stroke by middle cerebral artery occlusion (MCAO) was established, and 16S ribosomal RNA (rRNA) gene sequencing and metabolomic analysis were performed on the cecal content samples collected from the sham, model, and ANP-treated MCAO mice. The results showed that ANP significantly ameliorated cerebral infarct volume, improved neurological deficits, and reduced histopathological injuries in the ipsilateral ischemic cortex, hippocampus, and striatum. The latter effects included inhibition of neuronal death, increased Nissl bodies, and decreased cell apoptosis. Moreover, ANP reversed gut microbiota dysbiosis by modulating the abundance of bacteria whose effects may mitigate MCAO damage, such as the phyla Bacteroidetes and Firmicutes, the families Lachnospiraceae and Prevotellaceae, and the genera Alloprevotella and Roseburia. Microbial metabolites related to inflammation and neuroprotection, such as prostaglandin I2 and uridine, were also regulated by ANP treatment. Uridine, guanosine, and inosine might be potential neuromodulators produced by the gut microbiota in the ANP-treated group. Spearman correlation analysis revealed that these metabolites were intimately related to certain genera, including Alloprevotella, Lachnoclostridium, Enterorhabdus, Roseburia, Lachnospiraceae_UCG-006, and Colidextribacter. Our results demonstrated that alleviating gut microbiota dysbiosis is one of the mechanisms by which ANP protects against ischemic stroke and suggest that targeting Alloprevotella, Lachnoclostridium, Enterorhabdus, Roseburia, Lachnospiraceae_UCG-006, and Colidextribacter might be a potential anti-stroke therapy.

The organic dyes used in printing and dyeing wastewater have complex components, diverse structures and strong chemical stability, which make them not suitable for treatment and difficult to degrade in the environment. Porphyrins are macromolecules with 18 π electrons formed by four pyrrole molecules connected with a methylene bridge that has a stable structure. Porphyrin combines with iron to form an active intermediate with a structure similar to the cytochrome P450 enzyme, so they are widely used in the biomimetic field. In the current study, 5,10,15,20-tetra (4-carboxyphenyl) porphine ferric chloride (III) (Fe(III)TCPP) was used as a catalyst and iodosobenzene was used as an oxidant to explore the catalytic degradation of triphenylmethane dyes, such as rhodamine B (RhB) and malachite green (MG). The results of UV-Vis spectral analysis have shown that the conversion rate of the rhodamine B was over 90% when the amount of Fe(III)TCPP was 0.027 mM and the amount of iodosobenzene was eight equivalents. When the catalyst was 0.00681 mM and the amount of the oxidant was five equivalents, the conversion rate of the malachite green reached over 95%. This work provides a feasible method for the degradation of triphenylmethane dyes.

Abstract Background Myopia is the most common visual impairment in children and adolescents worldwide. This study described an economical and effective population-based screening pipeline and performed the project of a million scale children and adolescents myopia survey (CAMS), which will shed light on the further study of myopia from the level of epidemiology and precision medicine. Methods We developed a novel population-based screening pattern, an intelligent screening process and internet-based information transmission and analysis system to carry out the survey consisting of school children in Wenzhou, China. The examination items include unaided distance visual acuity, presenting distance visual acuity, and non-cycloplegic autorefraction. Myopia and high myopia were defined as spherical equivalent (SE) ≤ − 1.00 diopters (D) and SE ≤ − 6.00 D, respectively. Next, the reports of the vision checking were automatically sent to parents and the related departments. The CAMS project will be done two to four times annually with the support of the government. An online eyesight status information management system (OESIMS) was developed to construct comprehensive and efficient electronic vision health records (EVHRs) for myopia information inquiry, risk pre-warning, and further study. Results The CAMS completed the first-round of screening within 30 days for 99.41% of Wenzhou students from districts and counties, in June 2019. A total of 1,060,925 participants were eligible for CAMS and 1,054,251 (99.37% participation rate) were selected through data quality control, which comprised 1305 schools, and 580,609, 251,050 and 170,967 elementary, middle, and high school students. The mean age of participants was 12.21 ± 3.32 years (6–20 years), the female-to-male ratio was 0.82. The prevalence of myopia in elementary, middle, and high school students was 38.16%, 77.52%, and 84.00%, respectively, and the high myopia incidence was 0.95%, 6.90%, and 12.98%. Conclusions The CAMS standardized myopia screening model involves automating large-scale information collection, data transmission, data analysis and early warning, thereby supporting myopia prevention and control. The entire survey reduced 90% of staff, cost, and time consumption compared with previous surveys. This will provide new insights for decision support for public health intervention.

Reservoirs are important water sources of urban drinking water supply. Bacteria play an important role in the removal of organics in reservoirs, but some of them can pose a health risk to consumers. Knowledge of bacterial community composition in drinking water sources can favour the drinking water security safeguards. This study investigated the monthly composition and diversity of bacterial communities in three cascade reservoirs using high-throughput Illumina HiSeq sequencing over one hydrological year. The diversity and structure of the bacterial community showed distinct spatiotemporal variation. Mycobacterium, Acinetobacter, Sphingomonas, Sphingobacterium and Pseudomonas were the genera resistant to chlorine. In addition, Acinetobacter, Arcobacter, Mycobacterium, Pseudomonas and Staphylococcus were the main potential pathogenic genera. The bacterial community diversity and the average relative abundance of potential pathogenic genera detected in the wet season were higher than those in the dry season. Water temperature was found to be the main factor for the temporal variation. The spatial variation of bacterial community diversity and the average relative abundance of potential pathogenic genera were related to water current and the degree of water pollution, respectively. The results of this study can conduce the beneficial management of drinking water treatment processes. HIGHLIGHTS Bacterial communities in three cascade reservoirs showed spatiotemporal variation.; Bacterial diversity and potential pathogenic genera abundance were higher in the wet season.; Water temperature was the major factor leading to the temporal variation.; The spatial variation was related to water current and the degree of water pollution.;

Linezolid is an oxazolidinone antibacterial drug, and its therapeutic drug monitoring and individualized treatment have been challenged since its approval. With the in-depth clinical research of linezolid, we have changed our attitude toward its therapeutic drug monitoring and our view of individualized treatment. On the basis of summarizing the existing clinical studies, and based on the practical experience of each expert in their respective professional fields, we have formed this expert consensus. Our team of specialists is a multidisciplinary team that includes pharmacotherapists, clinical pharmacology specialists, critical care medicine specialists, respiratory specialists, infectious disease specialists, emergency medicine specialists and more. We are committed to the safe and effective use of linezolid in patients in need, and the promotion of its therapeutic drug monitoring.

Parkinson’s disease (PD) is the second most common neurodegenerative disease in the world; however, it lacks effective and safe treatments. Ginkgo biloba dropping pill (GBDP), a unique Chinese G. biloba leaf extract preparation, exhibits antioxidant and neuroprotective effects and has a potential as an alternative therapy for PD. Thus, the aims of this study were to evaluate the effects of GBDP in in vitro and in vivo PD models and to compare the chemical constituents and pharmacological activities of GBDP and the G. biloba extract EGb 761. Using liquid chromatography tandem-mass spectrometry, 46 GBDP constituents were identified. Principal component analysis identified differences in the chemical profiles of GBDP and EGb 761. A quantitative analysis of 12 constituents showed that GBDP had higher levels of several flavonoids and terpene trilactones than EGb 761, whereas EGb 761 had higher levels of organic acids. Moreover, we found that GBDP prevented 6-hydroxydopamine-induced dopaminergic neuron loss in zebrafish and improved cognitive impairment and neuronal damage in methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD mice. Although similar effects were observed after EGb 761 treatment, the neuroprotective effects were greater after GBDP treatment on several endpoints. In addition, in vitro results suggested that the Akt/GSK3β pathway may be involved in the neuroprotective effects of GBDP. These findings demonstrated that GBDP have potential neuroprotective effects in the treatment of PD.

Objective To identify the causes and suspected risk factors of the food poisoning incident, provide evidence for control measures, and provide reference for the investigation and prevention of similar food poisoning. Methods The case investigations and on-site hygiene surveys were carried out by actively searching for cases through epidemiological and laboratory testing techniques. Then, the relevant food, external environment and case samples were collected for laboratory testing to determine the suspicious meals and food of this event. Results A total of 21 cases(including 2 confirmed cases) were screened out. The attack rate of this event was 12.96%(21/162), and the main clinical symptoms were vomiting(95.24%,20/21), abdominal pain(66.67%,14/21), nausea(66.67%,14/21) and diarrhea(57.14%,12/21). Data from the case control studies result showed that the suspected food was the rice left over from the dinner on October 16th(OR=18.18, 95%CI: 2.05-161.38). Two cases were detected Staphylococcus aureus and enterotoxin type B in an anal swab and vomit. Conclusion The cause of this food poisoning outbreak was the leftover rice from the canteen on the 16th dinner, which was contaminated by Staphylococcus aureus and enterotoxin type B. Rice was placed at room temperature for about 5 hours and was not heated thoroughly before eating, which was a risk factor for this event. Food safety supervision and food safety education for canteen employees should be further strengthened to improve food safety awareness and prevent similar incidents.

Inflammation is a vital protective response in living systems and closely related to various diseases. As a member of the reactive oxygen species (ROS) family, peroxynitrite (ONOO−) is involved in the organism’s inflammatory process and considered as an important biomarker of inflammation. Therefore, the construction of a simple, rapid, and sensitive tool for detecting ONOO− is of great importance for the diagnosis of inflammation. In this study, we constructed the new near-infrared fluorescence probe BDP-ENE-S-Py+ based on BODIPY dye, which has the advantages of fast response speed (2 min), good selectivity, and a high signal-to-noise ratio. Moreover, the probe had a good linear relationship (LOD = 120 nM) when the ONOO− concentration was 10–35 µM. In addition, BDP-ENE-S-Py+ could detect exogenous ONOO− in liver cancer cells without interference from other reactive oxygen species and visualize the fluctuations in ONOO− concentrations in cells. More importantly, BDP-ENE-S-Py+ was able to track the upregulation of ONOO− content in a mouse model of peritonitis induced by LPS. This work demonstrated that the near-infrared fluorescent probe for visualizing ONOO− level fluctuations could provide a promising tool for inflammation-related studies.

Drought is the main abiotic stress limiting soybean production worldwide and seriously limits the reproductive growth of soybean. To elucidate the molecular mechanisms of drought stress response in soybean seed developmental stages, transcriptome analysis was performed on five seed developmental stages under drought stress and control conditions. Thousands of genes were found to change in expression level under drought stress, GO and KEGG enrichment analysis showed that differentially expressed genes (DEGs) were involved in drought resistance at every stage or tissue, but there were very few DEGs at the primary stage of seed development, which indicated that the seeds at the primary developmental stage were influenced little by drought stress. There was no shared DEG among all five stages or tissues, this indicated that they have different mechanisms to resist drought stress. Furthermore, we investigated DEGs associated with drought response at different stages to identify candidate regulators of drought stress response during soybean seed development. These genes are associated with metabolic and regulatory networks, among others. Taken together, the results will expand our understanding of the adaptation of soybean to drought stress and provide new insights into the molecular mechanisms of soybean drought tolerance development.

Time-series single-cell RNA sequencing (scRNA-seq) provides a breakthrough in modern biology by enabling researchers to profile and study the dynamics of genes and cells based on samples obtained from multiple time points at an individual cell resolution. However, cell asynchrony and an additional dimension of multiple time points raises challenges in the effective use of time-series scRNA-seq data for identifying genes and cell subclusters that vary over time. However, no effective tools are available. Here, we propose scTITANS (https://github.com/ZJUFanLab/scTITANS), a method that takes full advantage of individual cells from all time points at the same time by correcting cell asynchrony using pseudotime from trajectory inference analysis. By introducing a time-dependent covariate based on time-series analysis method, scTITANS performed well in identifying differentially expressed genes and cell subclusters from time-series scRNA-seq data based on several example datasets. Compared to current attempts, scTITANS is more accurate, quantitative, and capable of dealing with heterogeneity among cells and making full use of the timing information hidden in biological processes. When extended to broader research areas, scTITANS will bring new breakthroughs in studies with time-series single cell RNA sequencing data.

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by progressive and irreversible loss of lung function. Clinically safe and efficacious drug treatments for IPF are lacking. Pirfenidone (an anti-inflammatory, antioxidant and anti-fibrotic small-molecule drug) is considered a promising treatment for IPF. Unfortunately, several disadvantages of pirfenidone caused by traditional administration (e.g., gastrointestinal reactions, short elimination half-life) hinder its implementation. We designed pirfenidone pH-sensitive liposomes (PSLs) to target the acidic microenvironment of IPF and act directly at the disease site through pulmonary administration. Pirfenidone was encapsulated in liposomes to extend its half-life, and modified with polyethylene glycol on the surface of liposomes to improve the permeability of the mucus layer in airways. In vitro, the cytotoxicity of pirfenidone PSLs to pulmonary fibroblasts was increased significantly at 48 h compared with that using pirfenidone. In a murine and rat model of bleomycin-induced pulmonary fibrosis, pirfenidone PSLs inhibited IPF development and increased PSL accumulation in the lungs compared with that using pirfenidone solution or phosphate-buffered saline. Pirfenidone PSLs had potentially fewer side effects and stronger lung targeting. These results suggest that pirfenidone PSLs are promising preparations for IPF treatment.

Background: Myopia is the most common visual impairment among Chinese children and adolescents. The purpose of this study is to explore key interventions for myopia prevalence, especially for early-onset myopia and high myopia.Methods: Univariate and multivariate analyses were conducted to evaluate potential associations between risk factor exposure and myopia. LASSO was performed to prioritize the risk features, and the selected leading factors were used to establish the assembled simulation model. Finally, two forecasting models were constructed to predict the risk of myopia and high myopia.Results: Children and adolescents with persistently incorrect posture had a high risk of myopia (OR 7.205, 95% CI 5.999–8.652), which was 2.8 times higher than that in students who always maintained correct posture. In the cohort with high myopia, sleep time of less than 7 h per day (OR 9.789, 95% CI 6.865–13.958), incorrect sitting posture (OR 8.975, 95% CI 5.339–15.086), and siblings with spherical equivalent

Allergens have been identified as potential triggers in patients with atopic dermatitis (AD). Patients with AD are highly sensitive to cockroach allergen. The underlying mechanism, however, remains undetermined. Here, we established a cockroach allergen–induced AD-like mouse model, and we demonstrate that repeated exposure to cockroach allergen led to aggravated mouse skin inflammation, characterized by increased type 2 immunity, type 2 innate lymphoid cells (ILC2s), and mast cells. Increased mast cells were also observed in patients with AD. Mast cell–deficient mice (KitW-sh/W-sh) showed diminished skin inflammation, suggesting that mast cells are required in allergen-induced skin inflammation. Furthermore, DC immunoreceptor (DCIR) is upregulated in skin mast cells of patients with AD and mediates allergen binding and uptake. DCIR–/– mice or reconstituted KitW-sh/W-sh mice with DCIR–/– mast cells showed a significant reduction in AD-like inflammation. Both in vitro and in vivo analyses demonstrate that DCIR–/– mast cells had reduced IgE-mediated mast cell activation and passive cutaneous anaphylaxis. Mechanistically, DCIR regulates allergen-induced IgE-mediated mast cell ROS generation and oxidation of calmodulin kinase II (ox-CaMKII). ROS-resistant CaMKII (MM-VVδ) prevents allergen-induced mast cell activation and inflammatory mediator release. Our study reveals a DCIR/ROS/CaMKII axis that controls allergen-induced mast cell activation and AD-like inflammation.

Objective A 13C isotope labeled internal standard-gas chromatography-tandem mass spectrometric (GC-MS/MS) with dispersive solid phase extraction (d-SPE) method was developed for the simultaneous determination of 7 polybrominated diphenyl ethers (PBDEs) residues in milk. Methods After adding13C12 isotope internal standard and extracted with 1% acetic acid acetonitrile, purified with the new Z-Sep+C18 dispersive agent, the analytes in the sample solutions were seperated by DB-5 column (30 m×0.25 mm, 0.25 μm). Operated by electron impact ion source (EI) with multiple reactions monitoring (MRM) mode, the samples were analyzed by gas chromatography-tandem mass spectrometer. The quantifications were performed by the isotope internal standard method with matrix-matched calibration standards. Results Good linearity was obtained for 7 PBDEs in the concentration range of 0.500-100 ng/mL with correlation coefficients (r) above 0.999. Recoveries for 7 PBDEs at three spiked levels of 0.1, 1.0, and 10 μg/kg were in the range of 89.7%-102.9% with relative standard deviations (RSDs, n = 6) of 3.8%-8.3%. The limits of detection and the limits of quantification were in the ranges of 2.4-9.8 and 7.5-30 ng/kg, respectively. Conclusion The established method was simple, efficient and sensitive, and could be applied in the determination of 7 PBDEs in milk.

Abstract Background Liver ischemia/reperfusion (I/R) injury is an inevitable pathological phenomenon in various clinical conditions, such as liver transplantation, resection surgery, or shock, which is the major cause of morbidity and mortality after operation. Ginkgo Biloba Dropping Pill (GBDP) is a unique Chinese Ginkgo Biloba leaf extract preparation that exhibits a variety of beneficial biological activities. The aim of this study is to investigate the protective effects of GBDP on the liver I/R injury both in the in vitro and in vivo. Methods Hypoxia/reoxygenation (H/R) experiments were performed in alpha mouse liver 12 (AML-12) cells and primary hepatocytes, which were pretreated with GBDP (60 or 120 µg/mL) followed by incubation in a hypoxia chamber. Cell viability was detected by 3-(4,5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide (MTT) assay. Annexin V staining as well as western blot analysis of apoptosis-related proteins was performed to detect the protective effect of GBDP on cell apoptosis induced by H/R injury. C57BL/6 mice were used to establish the liver I/R injury model, and were pretreated with GBDP (100 or 200 mg/kg/day, i.g.) for two weeks. The liver damage was evaluated by detection of plasma levels of alanine transaminase (ALT) and aspartate transaminase (AST), as well as histopathological examinations. Liver inflammation was determined by detecting the secretion of pro-inflammatory cytokines and neutrophil infiltration through enzyme-linked immunosorbent assay (ELISA) and myeloperoxidase (MPO) immunohistochemistry staining. Finally, Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick and labeling (TUNEL) staining and western blot analysis of apoptosis-related proteins were used to investigate the anti-apoptotic effect of GBDP in mice. Results In the in vitro study, GBDP pretreatment improved the cell viability of AML-12 cells in the H/R injury model. Similarly, the same result was found in the primary hepatocytes isolated from C57BL/6 mice. Moreover, GBDP decreased the number of apoptotic cells and reduced the expression of apoptosis-related proteins induced by H/R injury. In the in vivo study, oral administration of GBDP ameliorated liver injury evidenced by a significant decline in the levels of ALT and AST. Furthermore, the result of hematoxylin and eosin (H&E) staining showed that GBDP reduced the size of necrosis area in the liver tissue. In addition, the decreased infiltration of neutrophils and secretion of pro-inflammatory cytokines indicated that GBDP may play an anti-inflammatory effect. More importantly, GBDP reduced TUNEL-positive cells and the expression of apoptosis-related proteins in the liver indicating GBDP has anti-apoptotic effects. Conclusions Our findings elucidated that GBDP has potential effects for protecting against liver I/R injury characterized by its anti-apoptotic, anti-necrotic, and anti-inflammatory properties, which would promisingly make contributions to the exploration of therapeutic strategies in the liver I/R injury.

Abstract Background In the UK certain groups with pre-disposing conditions are eligible for vaccination with the pneumococcal polysaccharide vaccine (PPV23). Uptake of the vaccine in these individuals has not been reported for 10 years. Hence this study investigated the rates of pneumococcal vaccination, the time to vaccination since diagnosis, and factors associated with vaccination in individuals aged 18–64 years with certain underlying medical conditions. Methods A retrospective database analysis was conducted using the Clinical Practice Research Datalink (CPRD). Individuals aged 18 to 64 years who had a diagnosis for underlying medical conditions of interest at the index date (January 1, 2011 to December 31, 2015) were included in this study. Both underlying conditions and pneumococcal vaccination were identified using Read codes. A multivariable logistic regression model was used to identify factors associated with pneumococcal vaccination. Results A total of 99,153 individuals with underlying medical conditions were included in this study. Within 1 year of follow-up, 13.6% had received pneumococcal vaccination. This figure rose to 32.0% after 4 years of follow-up. The mean time between diagnosis and vaccination was 148.7 days across the overall cohort. Based on multivariate analysis of results, individuals with chronic heart disease, chronic kidney disease, chronic liver disease, chronic respiratory disease or diabetes mellitus were significantly less likely (P

To determine prevalence of, seroprevalence of, and potential exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among a cohort of evacuees returning to the United States from Wuhan, China, in January 2020, we conducted a cross-sectional study of quarantined evacuees from 1 repatriation flight. Overall, 193 of 195 evacuees completed exposure surveys and submitted upper respiratory or serum specimens or both at arrival in the United States. Nearly all evacuees had taken preventive measures to limit potential exposure while in Wuhan, and none had detectable SARS-CoV-2 in upper respiratory tract specimens, suggesting the absence of asymptomatic respiratory shedding among this group at the time of testing. Evidence of antibodies to SARS-CoV-2 was detected in 1 evacuee, who reported experiencing no symptoms or high-risk exposures in the previous 2 months. These findings demonstrated that this group of evacuees posed a low risk of introducing SARS-CoV-2 to the United States.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as the etiologic agent associated with coronavirus disease, which emerged in late 2019. In response, we developed a diagnostic panel consisting of 3 real-time reverse transcription PCR assays targeting the nucleocapsid gene and evaluated use of these assays for detecting SARS-CoV-2 infection. All assays demonstrated a linear dynamic range of 8 orders of magnitude and an analytical limit of detection of 5 copies/reaction of quantified RNA transcripts and 1 x 10−1.5 50% tissue culture infectious dose/mL of cell-cultured SARS-CoV-2. All assays performed comparably with nasopharyngeal and oropharyngeal secretions, serum, and fecal specimens spiked with cultured virus. We obtained no false-positive amplifications with other human coronaviruses or common respiratory pathogens. Results from all 3 assays were highly correlated during clinical specimen testing. On February 4, 2020, the Food and Drug Administration issued an Emergency Use Authorization to enable emergency use of this panel.

We describe the contact investigation for an early confirmed case of coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in the United States. Contacts of the case-patient were identified, actively monitored for symptoms, interviewed for a detailed exposure history, and tested for SARS-CoV-2 infection by real-time reverse transcription PCR (rRT-PCR) and ELISA. Fifty contacts were identified and 38 (76%) were interviewed, of whom 11 (29%) reported unprotected face-to-face interaction with the case-patient. Thirty-seven (74%) had respiratory specimens tested by rRT-PCR, and all tested negative. Twenty-three (46%) had ELISA performed on serum samples collected ≈6 weeks after exposure, and none had detectable antibodies to SARS-CoV-2. Among contacts who were tested, no secondary transmission was identified in this investigation, despite unprotected close interactions with the infectious case-patient.

The etiologic agent of an outbreak of pneumonia in Wuhan, China, was identified as severe acute respiratory syndrome coronavirus 2 in January 2020. A patient in the United States was given a diagnosis of infection with this virus by the state of Washington and the US Centers for Disease Control and Prevention on January 20, 2020. We isolated virus from nasopharyngeal and oropharyngeal specimens from this patient and characterized the viral sequence, replication properties, and cell culture tropism. We found that the virus replicates to high titer in Vero-CCL81 cells and Vero E6 cells in the absence of trypsin. We also deposited the virus into 2 virus repositories, making it broadly available to the public health and research communities. We hope that open access to this reagent will expedite development of medical countermeasures.

Abstract For multicellular organisms, cell-cell communication is essential to numerous biological processes. Drawing upon the latest development of single-cell RNA-sequencing (scRNA-seq), high-resolution transcriptomic data have deepened our understanding of cellular phenotype heterogeneity and composition of complex tissues, which enables systematic cell-cell communication studies at a single-cell level. We first summarize a common workflow of cell-cell communication study using scRNA-seq data, which often includes data preparation, construction of communication networks, and result validation. Two common strategies taken to uncover cell-cell communications are reviewed, e.g., physically vicinal structure-based and ligand-receptor interaction-based one. To conclude, challenges and current applications of cell-cell communication studies at a single-cell resolution are discussed in details and future perspectives are proposed.

Objective: To investigate the effects of Ganjiang granule (GG) on cecal microflora and serum biochemical components in rats with constipation-predominant irritable bowel syndrome (IBS–C). Methods: Twenty-four Sprague–Dawley rats were randomly divided into four groups: control, model, GG, and probiotics. Rats in the model, GG, and probiotics groups received 3 °C tap water intragastrically; rats in the GG group were treated with GG; rats in the probiotics group were treated with probiotics. For all rats, enzyme-linked immunosorbent assay and colorimetry were used to assess serum biochemical components related to gastrointestinal function; 16S rRNA high-throughput sequencing was used to analyze the cecal microflora. Results: The serum level of 5-hydroxytryptamine (HT) was higher in the model group than in the control group (Z = −2.082, P = .037). The model group exhibited changes in cecal microflora: the relative abundances of Lactobacillus decreased (Z = −2.882, P = .004) and Dorea increased (t = −3.030, P = .023), compared with the control group. The GG and probiotics groups exhibited normal serum levels of 5-HT. The GG and probiotics groups exhibited improved serum levels of gastrin; the probiotics group exhibited an improved serum level of vasoactive intestinal peptide. Compared with the model group, The GG group exhibited greater relative abundance of Ruminococcus (Z = −2.402, P = .016); the probiotics group exhibited greater relative abundance of SMB53 (Z = −2.823, P = .005) and lower relative abundances of Desulfovibrio (Z = −2.823, P = .005) and Facklamia (Z = −2.608, P = .009). Conclusion: The effects of GG on IBS-C may be related to regulation of the serum level of 5-HT, as well as elevated relative abundance of beneficial bacteria in cecal microflora.

State-owned enterprises (SOEs) are important components of the Chinese economy. Although SOEs are generally considered inefficient in operations, China’s economy, which relies heavily on SOEs, has been highly successful over the last four decades. This indicates the importance of SOEs in China’s past and future economic success. Therefore, in this study, we review the literature on economic theories and 40 years of practice of Chinese SOEs and discuss implications for future research. Our review consists of four parts: the theories of SOEs and their reform, the performance and financing strategies of SOEs, corporate governance in SOEs, and corporate social responsibility in SOEs. Keywords: State-owned enterprises (SOE), Literature review, China

Abstract Background Deciphering intra‐ and inter‐tumoural heterogeneity is essential for understanding the biology of gastric cancer (GC) and its metastasis and identifying effective therapeutic targets. However, the characteristics of different organ‐tropism metastases of GC are largely unknown. Methods Ten fresh human tissue samples from six patients, including primary tumour and adjacent non‐tumoural samples and six metastases from different organs or tissues (liver, peritoneum, ovary, lymph node) were evaluated using single‐cell RNA sequencing. Validation experiments were performed using histological assays and bulk transcriptomic datasets. Results Malignant epithelial subclusters associated with invasion features, intraperitoneal metastasis propensity, epithelial–mesenchymal transition‐induced tumour stem cell phenotypes, or dormancy‐like characteristics were discovered. High expression of the first three subcluster‐associated genes displayed worse overall survival than those with low expression in a GC cohort containing 407 samples. Immune and stromal cells exhibited cellular heterogeneity and created a pro‐tumoural and immunosuppressive microenvironment. Furthermore, a 20‐gene signature of lymph node‐derived exhausted CD8+ T cells was acquired to forecast lymph node metastasis and validated in GC cohorts. Additionally, although anti‐NKG2A (KLRC1) antibody have not been used to treat GC patients even in clinical trials, we uncovered not only malignant tumour cells but one endothelial subcluster, mucosal‐associated invariant T cells, T cell‐like B cells, plasmacytoid dendritic cells, macrophages, monocytes, and neutrophils may contribute to HLA‐E‐KLRC1/KLRC2 interaction with cytotoxic/exhausted CD8+ T cells and/or natural killer (NK) cells, suggesting novel clinical therapeutic opportunities in GC. Additionally, our findings suggested that PD‐1 expression in CD8+ T cells might predict clinical responses to PD‐1 blockade therapy in GC. Conclusions This study provided insights into heterogeneous microenvironment of GC primary tumours and organ‐specific metastases and provide support for precise diagnosis and treatment.

As a popular research subject in the field of computer vision, knowledge distillation (KD) is widely used in semantic segmentation (SS). However, based on the learning paradigm of the teacher–student model, the poor quality of teacher network feature knowledge still hinders the development of KD technology. In this paper, we investigate the output features of the teacher–student network and propose a feature condensation-based KD network (FCKDNet), which reduces pseudo-knowledge transfer in the teacher–student network. First, combined with the pixel information entropy calculation rule, we design a feature condensation method to separate the foreground feature knowledge from the background noise of the teacher network outputs. Then, the obtained feature condensation matrix is applied to the original outputs of the teacher and student networks to improve the feature representation capability. In addition, after performing feature condensation on the teacher network, we propose a soft enhancement method of features based on spatial and channel dimensions to improve the dependency of pixels in the feature maps. Finally, we divide the outputs of the teacher network into spatial condensation features and channel condensation features and perform distillation loss calculation with the student network separately to assist the student network to converge faster. Extensive experiments on the public datasets Pascal VOC and Cityscapes demonstrate that our proposed method improves the baseline by 3.16% and 2.98% in terms of mAcc, and 2.03% and 2.30% in terms of mIoU, respectively, and has better segmentation performance and robustness than the mainstream methods.