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A large number of SARS-related coronaviruses (SARSr-CoV) have been detected in horseshoe bats since 2005 in different areas of China. However, these bat SARSr-CoVs show sequence differences from SARS coronavirus (SARS-CoV) in different genes (S, ORF8, ORF3, etc) and are considered unlikely to represent the direct progenitor of SARS-CoV. Herein, we report the findings of our 5-year surveillance of SARSr-CoVs in a cave inhabited by multiple species of horseshoe bats in Yunnan Province, China. The full-length genomes of 11 newly discovered SARSr-CoV strains, together with our previous findings, reveals that the SARSr-CoVs circulating in this single location are highly diverse in the S gene, ORF3 and ORF8. Importantly, strains with high genetic similarity to SARS-CoV in the hypervariable N-terminal domain (NTD) and receptor-binding domain (RBD) of the S1 gene, the ORF3 and ORF8 region, respectively, were all discovered in this cave. In addition, we report the first discovery of bat SARSr-CoVs highly similar to human SARS-CoV in ORF3b and in the split ORF8a and 8b. Moreover, SARSr-CoV strains from this cave were more closely related to SARS-CoV in the non-structural protein genes ORF1a and 1b compared with those detected elsewhere. Recombination analysis shows evidence of frequent recombination events within the S gene and around the ORF8 between these SARSr-CoVs. We hypothesize that the direct progenitor of SARS-CoV may have originated after sequential recombination events between the precursors of these SARSr-CoVs. Cell entry studies demonstrated that three newly identified SARSr-CoVs with different S protein sequences are all able to use human ACE2 as the receptor, further exhibiting the close relationship between strains in this cave and SARS-CoV. This work provides new insights into the origin and evolution of SARS-CoV and highlights the necessity of preparedness for future emergence of SARS-like diseases.

In the early February, 2020, we called up an experts’ committee with more than 30 Chinese experts from 11 national medical academic organizations to formulate the first edition of consensus statement on diagnosis, treatment and prevention of coronavirus disease 2019 (COVID-19) in children, which has been published in this journal. With accumulated experiences in the diagnosis and treatment of COVID-19 in children, we have updated the consensus statement and released the second edition recently. The current version in English is a condensed version of the second edition of consensus statement on diagnosis, treatment and prevention of COVID-19 in children. In the current version, diagnosis and treatement criteria have been optimized, and early identification of severe and critical cases is highlighted. The early warning indicators for severe pediatric cases have been summarized which is utmost important for clinical practice. This version of experts consensus will be valuable for better prevention, diagnosis and treatment of COVID-19 in children worldwide.  

A synthetic-turbulence and temperature-fluctuation-generation method is developed and embedded in large-eddy simulations to investigate the effects of weak stable stratification (i.e. Richardson number Ri≤1) on turbulence and dispersion following a simulated rural-to-urban transition. The modelling approach is validated by comparing predictions of mean velocity, turbulent stresses, and point-source dispersion against data from a wind-tunnel experiment that simulates a stable atmospheric boundary layer (Ri=0.21) approaching a regular array of uniform rectangular blocks. The depth of the internal boundary layer (IBL) that develops from the leading edge of the block array is determined using the wall-normal turbulent stress method proposed by Sessa et al. (J Wind Eng Ind Aerodyn 182:189–291, 2018). This shows that the depth and growth rate of the IBL are sensitive to the thermal stability and the turbulence kinetic energy (TKE) prescribed at the inlet, such that the IBL depth reduces as the TKE of the inflow is reduced while maintaining the same Ri, or as the Ri is increased while maintaining the same inflow TKE. When a ground level line source is introduced it is found that increasing Ri evidently reduces the vertical scalar fluxes at the canopy height, while increasing the mean concentrations within the streets. Furthermore, as with IBL development it is found that for a given value of Ri the effect of stratification becomes more pronounced as the inflow level of TKE is reduced, affecting scalar fluxes within and above the canopy, and volume-averaged mean concentrations within the streets.

Triple-negative breast cancer (TNBC) is a refractory type of breast cancer that does not yet have clinically effective drugs. The aim of this study is to investigate the synergistic effects and mechanisms of resveratrol combined with cisplatin on human breast cancer MDA-MB-231 (MDA231) cell viability, migration, and invasion in vivo and in vitro. In vitro, MTS assays showed that resveratrol combined with cisplatin inhibits cell viability as a concentration-dependent manner, and produced synergistic effects (CI < 1). Transwell assay showed that the combined treatment inhibits TGF-β1-induced cell migration and invasion. Immunofluorescence assays confirmed that resveratrol upregulated E-cadherin expression and downregulated vimentin expression. Western blot assay demonstrated that resveratrol combined with cisplatin significantly reduced the expression of fibronectin, vimentin, P-AKT, P-PI3K, P-JNK, P-ERK, Sma2, and Smad3 induced by TGF-β1 (p < 0.05), and increased the expression of E-cadherin (p < 0.05), respectively. In vivo, resveratrol enhanced tumor growth inhibition and reduced body weight loss and kidney function impairment by cisplatin in MDA231 xenografts, and significantly reduced the expressions of P-AKT, P-PI3K, Smad2, Smad3, P-JNK, P-ERK, and NF-κB in tumor tissues (p < 0.05). These results indicated that resveratrol combined with cisplatin inhibits the viability of breast cancer MDA231 cells synergistically, and inhibits MDA231 cells invasion and migration through Epithelial-mesenchymal transition (EMT) approach, and resveratrol enhanced anti-tumor effect and reduced side of cisplatin in MDA231 xenografts. The mechanism may be involved in the regulations of PI3K/AKT, JNK, ERK and NF-κB expressions.

The strategic design of donor–acceptor (D-A) conjugated porous polymers has emerged as a pivotal methodology for advancing efficient photocatalytic hydrogen evolution. However, conventional D-A polymeric architectures face inherent limitations: excessively strong acceptor units may lower the LUMO energy level, compromising proton (H+) reduction capability, while weak D-A interactions result in inadequate light-harvesting capacity and insufficient photogenerated electrons, ultimately diminishing photocatalytic activity. To address these challenges, we developed a new D1-A-D2 conjugated porous polymer (CPP) system. The strategic incorporation of a secondary donor benzothiophene (DBBTh) unit enabled precise bandgap engineering in D1-A-D2 CPPs. Experimental results demonstrate that DBBTh integration significantly enhances both light absorption efficiency and proton reduction ability. Under visible-light irradiation (λ > 420 nm), the Py-BKh1 photocatalyst achieved a hydrogen evolution rate (HER) of 10.2 mmol h−1 g−1 with an apparent quantum yield (AQY) of 9.5% at 500 nm. This work provides a groundbreaking paradigm for designing high-performance organic photocatalysts.

We proposed a method to represent scientific papers by a complex network, which combines the approaches of neural and complex networks.Its novelty is representing a paper by a word branch, which carries the sequential structure of words in sentences. The branches are generated by the attention mechanism in deep learning models. We connected those branches at the positions of their common words to generate networks, called word-attention networks, and then detect their communities, defined as topics.Those detected topics can carry the sequential structure of words in sentences, represent the intra- and inter-sentential dependencies among words, and reveal the roles of words playing in them by network indexes.The parameter setting of our method may depend on practical data. Thus it needs human experience to find proper settings.Our method is applied to the papers of the PNAS, where the discipline designations provided by authors are used as the golden labels of papers’ topics.This empirical study shows that the proposed method outperforms the Latent Dirichlet Allocation and is more stable.

One-dimensional urban models embedded in mesoscale numerical models may place several grid points within the urban canopy. This requires an accurate parametrization for shear stresses (i.e. vertical momentum fluxes) including the dispersive stress and momentum sinks at these points. We used a case study with a packing density of 33% and checked rigorously the vertical variation of spatially-averaged total shear stress, which can be used in a one-dimensional column urban model. We found that the intrinsic spatial average, in which the volume or area of the solid parts are not included in the average process, yield greater time–spatial average of total stress within the canopy and a more evident abrupt change at the top of the buildings than the comprehensive spatial average, in which the volume or area of the solid parts are included in the average.

Effectively regulating monomer and excimer emission in a singular supramolecular luminous platform is challenging due to high difficulty of precise control over its aggregation and dispersion behavior when subjected to external stimuli. Here, we show a metallo-cage ( MTH ) featuring a triple helical motif that displays a unique dual emission. It arises from both intramolecular monomer and intermolecular excimer, respectively. The distorted molecular conformation and the staggered stacking mode of MTH excimer are verified through single crystal X-ray diffraction analysis. These structural features facilitate the switch between monomer and excimer emission, which are induced by changes in concentration and temperature. Significantly, adjusting the equilibrium between these two states in MTH enables the production of vibrant white light emission in both solution and solid state. Moreover, when combined with a PMMA (polymethyl methacrylate) substrate, the resulting thin films can serve as straightforward fluorescence thermometer and thermally activated information encryption materials. Effectively regulating monomer and excimer emission in a singular supramolecular luminous platform is challenging due to high difficulty of precise control over its aggregation and dispersion behavior when subjected to external stimuli. Here, the authors report a metallo-cage featuring a triple helical motif that displays a unique dual emission.

Delirium and cognitive decline are linked to clinically relevant anesthetics in the vulnerable elderly population, prompting the need for new and safer anesthetic strategies. Most general anesthetics potentiate the activity of GABA A receptors. However, these drugs act on myriad other targets, causing unwanted effects. Dexmedetomidine (Dex), a selective α 2 adrenergic receptor agonist, is associated with reduced incidences of delirium and cognitive decline in the elderly. Unfortunately, despite its sedative effect, Dex is not suitable for general anesthesia when used alone. We previously demonstrated that enhancing Dex with low doses of either sevoflurane or propofol resulted in a potent general anesthetic that was rapidly reversible. In this study we assessed whether Dex enhanced by magnesium (Mg 2+ ) infusion could produce a general anesthetic. Mg 2+ is an essential ion in the body, possessing sedative effects attributable to antagonizing NMDA receptors and voltage-gated Ca 2+ channels and it may indirectly potentiate GABAergic signaling. Mg 2+ has been shown to be neuroprotective and safe to use even in pregnant women. Mg 2+ is a safer adjunct agent than either sevoflurane or propofol. For this study, rats of both sexes were anesthetized with a combination of Dex and Mg 2+ and then underwent procedures to determine the efficacy of the anesthetic. Dex with Mg 2+ produced an effective general anesthetic that was reversed by a combination of low dose atipamezole, an α 2 competitive antagonist, and caffeine. We compared Dex supplemented with Mg 2+ to Dex supplemented with midazolam, a selective positive GABA A modulator and found that immobility, antinociception, EEG signatures, and hemodynamic profiles were comparable. Our findings showed that activation of α 2 receptors by Dex, with blockade of NMDA receptors/ Ca 2+ channels by Mg 2+ produce an effective and reversible general anesthetic with possible neuroprotective properties that may be appropriate for cognitively vulnerable patients like the elderly.

Objective Single-stranded DNA-binding protein 1 (SSBP1) plays an important role in DNA repair processes and the maintenance of genomic stability. The aim of this study was to evaluate the expression of SSBP1 and its prognostic value in lung adenocarcinoma (LUAD) using bioinformatics approaches. Methods We applied databases including UALCAN, Kaplan-Meier plotter, LinkedOmics, Webgestalt, cBioPortal and TIMER2.0 in this study. Results We found that SSBP1 expression was up-regulated in LUAD samples and was correlated with clinicopathological features including age, cancer stage, and nodal metastasis status by the UALCAN analysis. Multivariate Cox regression analysis by the Kaplan-Meier plotter showed that high SSBP1 expression was independently correlated with poor overall survival (hazard ratio = 1.63, 95% confidence interval: 1.08−2.46, logrank P = 0.02). The LinkedOmics analysis showed that 5078 genes were positively correlated with SSBP1 expression, whereas 7905 genes were negatively correlated with SSBP1 in LUAD. Functional enrichment analysis using the Webgestalt tool showed that for SSBP1 and the genes positively correlating with it, the significantly enriched biological process was ribosomal large subunit biogenesis, and the significantly enriched pathway was proteasome. According to the cBioPortal database, the frequency of SSBP1 alterations was 1.7% in LUAD patients, and patients with SSBP1 alterations had worse prognosis (logrank P = 4.26e-05) compared with those unaltered for SSBP1. Finally, SSBP1 expression was negatively correlated with B cell infiltration level (Rho = −0.193, P = 1.54e-05) and the expression of B cell biomarkers including CD79A and CD19. Conclusion Our results suggest that SSBP1 may be a prognostic marker for human LUAD.