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Exercise prescriptions play a vital role in the prevention and treatment of chronic diseases. A consensus regarding exercise prescription is important for physical health. The “Consensus statement of Chinese experts on exercise prescription” (hereinafter referred to as “Expert Consensus”) divides exercise prescription into two categories: fitness exercise prescription and medical exercise prescription. Traditional Chinese fitness exercises, exercise risk, exercise prescription, and basic precautions for exercise prescription are explained.

RNA N6-methyladenosine (m6A) methylation is the most abundant and conserved RNA modification in eukaryotes. It participates in the regulation of RNA metabolism and various pathophysiological processes. Non-coding RNAs (ncRNAs) are defined as small or long transcripts which do not encode proteins and display numerous biological regulatory functions. Similar to mRNAs, m6A deposition is observed in ncRNAs. Studying RNA m6A modifications on ncRNAs is of great importance specifically to deepen our understanding of their biological roles and clinical implications. In this review, we summarized the recent research findings regarding the mutual regulation between RNA m6A modification and ncRNAs (with a specific focus on microRNAs, long non-coding RNAs, and circular RNAs) and their functions. We also discussed the challenges of m6A-containing ncRNAs and RNA m6A as therapeutic targets in human diseases and their future perspective in translational roles.

Abstract Droplet transmission is the primary infection route for respiratory diseases like COVID‐19 and influenza, but small and low‐cost wearable droplet detection devices are a significant challenge. Herein, a respiratory droplet micro‐sensor based on graphene oxide quantum dots (GOQDs) assembled onto SiO2 microspheres by the nebulized natural deposition is presented. Benefiting from the energy dissipation of the microsphere to droplets, the sensor can detect droplets as far as 2 m from coughing. With this sensor, droplet signal variations caused by some factors like distance, speech, angles, and wind directions are explored, and the effectiveness of different protective measures in preventing droplet transmission is evaluated. This droplet detection technology is expected to be utilized for the development of personal detection and protection devices against infectious respiratory diseases.

Mountain gravity wave characteristics are important for analyzing the nighttime heavy rainfall events occurring in Sichuan. Based on the GPM satellite precipitation data, FY-4A satellite cloud data, and ERA5 reanalysis data, we analyze the mesoscale characteristics of a nighttime rainstorm with a gravity wave that occurred on 10-11 July 2018 in the northeastern Sichuan Basin mountains. The results are as follows. (1) The oscillatory feature of cloud water content and the wavelike variation of the potential temperature field reflect, to some extent, the influence of the fluctuations on the mesoscale system. (2) The fluctuation trends of wind vertical shear index, thermal helicity, and moisture helicity appear during the development of waves, indicating the characteristics of gravity waves. (3) The areas with large values of wind vertical shear index, the extreme center of thermal helicity, and moisture helicity are consistent well with the heavy precipitation regions. (4) The gravity wave may be formed by the interaction of topographic disturbances, shear instability, and non-geostrophic equilibrium, which enhance the rainstorm. The regions with a small value of the Richardson number and a nonzero value of the nonlinear equilibrium equation can indicate the location and movement direction of the rainbands. Diagnosis of Richardson number shows that the vertical shear instability is formed before the mesoscale wave is excited, but it decreases with increasing fluctuations, which indicates that part of the energy of the waves comes from the unstable flow.

Abstract While recent years have witnessed the unprecedented success of deep convolutional neural networks (CNNs) and vision transformers in single‐image super‐resolution (SISR), the degradation assumptions are simple and usually bicubic downsampling. Thus, their performances will drop dramatically when the actual degradation does not match this assumption, and they lack the capability to handle multiple degradations (e.g. Gaussian noise, bicubic downsizing, and salt & pepper noise). To address the issues, in this paper, the authors propose a joint SR model (JIRSR) that can effectively handle multiple degradations in a single model. Specifically, the authors build the parallel Transformer and CNN branches that complement each other through bidirectional feature fusion. Moreover, the authors also adopt a random permutation of different kinds of noise and resizing operations to build the training datasets. Extensive experiments on classical SR, denoising, and multiple degradation removal demonstrate that the authors’ JIRSR achieves state‐of‐the‐art (SOTA) performance on public benchmarks. Concretely, the authors’ JIRSR outperforms the second‐best model by 0.23 to 0.74 dB for multiple degradations removal and is 0.20 to 0.36 dB higher than the SOTA methods on the Urban100 dataset under the ×4 SR task.

Abstract Dynamic multiobjective optimization is a significant challenge in accurately capturing changes in Pareto optimal sets (PS), encompassing both location and manifold changes. Existing approaches primarily focus on tracking changes in the location of the PS, often overlooking the potential impact of changes in the PS manifold, which can be decomposed into rotation and distortion changes. Such oversights can lead to a reduction in the overall performance of an algorithm. To address this issue, a prediction method based on joint subspace and correlation alignment (PSCA) is proposed. PSCA leverages a subspace alignment strategy to effectively capture rotation change in the PS manifold while employing a correlation alignment strategy to capture distortion change. By integrating these two strategies, a quasi-initial population is generated that embodies the captured rotation and distortion change patterns in a new environment. Then, the promising individuals are selected from this quasi-initial population based on their nondominated relations and crowding degree to form the initial population in the new environment. To evaluate the effectiveness of PSCA, we conduct experiments on fourteen benchmark problems. The experimental results demonstrate that PSCA achieves significant improvements over several state-of-the-art algorithms.

Abstract Background DNA methylation may be involved in the regulation of malignant transformation from sinonasal inverted papilloma (SNIP) to squamous cell carcinoma (SCC). The study of gene methylation changes and screening of differentially methylated loci (DMLs) are helpful to predict the possible key genes in the malignant transformation of SNIP-SCC. Materials and methods Microarray dataset GSE125399 was downloaded from the Gene Expression Omnibus (GEO) database and differentially methylated loci (DMLs) were analyzed using R language (Limma package). ClusterProfiler R package was used to perform Gene Ontology (GO) analysis on up-methylated genes and draw bubble maps. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and its visualization analysis were analyzed to speculate the possible key Genes in SNIP-SCC malignant transformation. Subsequently, SNIP cases archived in our department were collected, tissue microarray was made, and immunohistochemical staining was performed to analyze the expression levels of UCKL1, GSTT1, HLA-G, MAML2 and NRGN in different grades of sinonasal papilloma tissues. Results Analysis of dataset GSE125399 identified 56 DMLs, including 49 upregulated DMLs and 7 downregulated DMLs. Thirty-one genes containing upregulated DNA methylation loci and three genes containing downregulated DNA methylation loci were obtained by methylation microarray annotation analysis. In addition, KEGG pathway visualization analysis of 31 up-methylated genes showed that there were four significantly up-methylated genes including UCKL1, GSTT1, HLA-G and MAML2, and one significantly down-methylated gene NRGN. Subsequently, compared with non-neoplasia nasal epithelial tissues, the expression of HLA-G and NRGN was upregulated in grade I, II, III and IV tissues, while the expression of MAML2 was lost. The protein expression changes of MAML2 and NRGN were significantly negatively correlated with their gene methylation levels. Conclusions By analyzing the methylation dataset, we obtained four up-regulated methylation genes UCKL1, GSTT1, HLA-G and MAML2 and one down-regulated gene NRGN. MAML2, a tumor suppressor gene with high methylation modification but loss of protein expression, and NRGN, a tumor gene with low methylation modification but upregulated protein expression, can be used as biological indicators to judge the malignant transformation of SNIP-SCC.

In this study, sensory evaluation and headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) were used to identify and analyze the volatile components of Yingjiang Camellia taliensis bud tea (usually called spore tea, marked as spore black tea YBH, spore white tea YBB) and Fengqing large-leaved species bud tea (marked as Fengqing black tea FQH, Fengqing white tea FQB) in order to investigate the aroma composition and differences between Yunnan Yingjiang Camellia taliensis bud tea and Fengqing large-leaved species bud tea. The results of HS-SPME-GC-MS showed that a total of 616 volatile metabolites from 16 categories were detected in the four tea samples. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) showed that in the comparison of two varieties of black tea, 8 unique differential metabolites were detected in YBH, and 7 unique differential metabolites in FQH, while in the comparison of two varieties of white tea, 3 unique differential metabolites were detected in YBB and 4 unique differential metabolites in FQB. The odor activity value (OAV) evaluation of the main characteristic differential volatile metabolites showed that (Z)-2-decenal and geraniol were the potential characteristic aromas to distinguish Yingjiang Camellia taliensis and Fengqing large-leaved species, (Z)-2-decenal (OAV>100) was an important aroma component of Yingjiang Camellia taliensis. It was speculated that damascenone (OAV>1) was the key substances for YBH to produce strong flower and fruit aroma. Caproic acid and linalyl acetate might be the main substances of YBB with natural flower fragrance. β-Ionone (OAV>10) was an important aroma component of Fengqing large-leaved species. It was speculated that benzaldehyde (OAV>1) was the main substance of FQH with flower aroma, and (Z)-2-decenal and caproic acid were the main substances of FQB with floral and fragrance. In summary, the aroma components of Yingjiang Camellia taliensis spore tea are richer than the control variety and the aroma of YBH is more fragrant.

Abstract The complexity of the tumor microenvironment (TME) is a crucial factor in lung adenocarcinoma (LUAD) progression. To gain deeper insights into molecular mechanisms of LUAD, we perform an integrative single-cell RNA sequencing (scRNA-seq) data analysis of 377,574 cells from 117 LUAD patient samples. By linking scRNA-seq data with bulk gene expression data, we identify a cluster of prognostic-related UPP1high tumor cells. These cells, primarily situated at the invasive front of tumors, display a stronger association with the immunosuppressive components in the TME. Our cytokine array analysis reveals that the upregulation of UPP1 in tumor cells leads to the increased release of various immunosuppressive cytokines, with TGF-β1 being particularly prominent. Furthermore, this UPP1 upregulation also elevates the expression of PD-L1 through the PI3K/AKT/mTOR pathway, which contributes to the suppression of CD8 + T cells. Cytometry by time-of-flight (CyTOF) analysis provides additional evidence of the role of UPP1 in shaping the immunosuppressive nature of the TME. Using patient-derived organoids (PDOs), we discover that UPP1high tumors exhibit relatively increased sensitivity to Bosutinib and Dasatinib. Collectively, our study highlights the immunosuppressive role of UPP1 in LUAD, and these findings may provide insights into the molecular features of LUAD and facilitate the development of personalized treatment strategies.

Abstract Background Exposure to PM2.5 has been implicated in a range of detrimental health effects, particularly affecting the respiratory system. However, the precise underlying mechanisms remain elusive. Methods To address this objective, we collected ambient PM2.5 and administered intranasal challenges to mice, followed by single-cell RNA sequencing (scRNA-seq) to unravel the heterogeneity of neutrophils and unveil their gene expression profiles. Flow cytometry and immunofluorescence staining were subsequently conducted to validate the obtained results. Furthermore, we assessed the phagocytic potential of neutrophils upon PM2.5 exposure using gene analysis of phagocytosis signatures and bacterial uptake assays. Additionally, we utilized a mouse pneumonia model to evaluate the susceptibility of PM2.5-exposed mice to Pseudomonas aeruginosa infection. Results Our study revealed a significant increase in neutrophil recruitment within the lungs of PM2.5-exposed mice, with subclustering of neutrophils uncovering subsets with distinct gene expression profiles. Notably, exposure to PM2.5 was associated with an expansion of PD-L1high neutrophils, which exhibited impaired phagocytic function dependent upon PD-L1 expression. Furthermore, PM2.5 exposure was found to increase the susceptibility of mice to Pseudomonas aeruginosa, due in part to increased PD-L1 expression on neutrophils. Importantly, monoclonal antibody targeting of PD-L1 significantly reduced bacterial burden, dissemination, and lung inflammation in PM2.5-exposed mice upon Pseudomonas aeruginosa infection. Conclusions Our study suggests that PM2.5 exposure promotes expansion of PD-L1high neutrophils with impaired phagocytic function in mouse lungs, contributing to increased vulnerability to bacterial infection, and therefore targeting PD-L1 may be a therapeutic strategy for reducing the harmful effects of PM2.5 exposure on the immune system.

Based on the conventional observation data, FY-4A TBB data, and ERA5 reanalysis data, a sustained extreme rainstorm event occurred in the western Sichuan Basin from August 14 to 18, 2020 was analyzed from the aspects of circulation background, mesoscale characteristics, water vapor and dynamic conditions, energy and instability conditions, etc. The results are as follows. The rainstorm was caused by the stable and limited movement of the western Pacific subtropical high, which blocked the eastward movement of the plateau low-trough and kept it stable in the western basin. At the same time, the shear line and jet stream were maintained in the middle and lower levels, and the surface cold air moving southward provides a favorable circulation background for the continuous extreme rainstorm. The formation, merging, and strengthening of mesoscale convective cloud clusters were affected by the topographic barrier, peripheral airflow of subtropical high, the shear line, and mesoscale low vortex. The strong center of the convective cloud cluster was maintained in the western part of the basin, which was the direct influence system of the rainstorm event. The rainstorm water vapor originated from the Bay of Bengal and the western Pacific Ocean. Under the influence of the topographic convergence uplift, a strong water vapor convergence center was formed in the western part of the basin. The each water vapor physical quantity in the rainstorm event presents extreme characteristics, providing sufficient water vapor conditions for the generation of continuous extreme rainstorm. Convergence and positive vorticity were developed throughout the rainstorm over the rainstorm area, which favored the enhancement of vertical upward movement. The rainstorm area was located in the frontal area of dense pseudo-equivalent potential temperature, and the dynamic forcing of the frontal area was beneficial to the upward transport of energy and water vapor, which made the rainstorm area maintain a high-energy and high-humidity environment continuously. The generalized wet potential vorticity anomalies were also found over the rainstorm area. The instability of the rainstorm area potential was mainly caused by its divergence component, which represented the coupling effect of horizontal divergence and potential stability. The positive divergence of potential was determined by the divergence component and the vertical wind shear component. The 850 hPa area with a high potential divergence value corresponded well with the heavy precipitation area.

Fine particulate matter (PM2.5) has been extensively implicated in the pathogenesis of neurodevelopmental disorders, but the underlying mechanism remains unclear. Recent studies have revealed that PM2.5 plays a role in regulating iron metabolism and redox homeostasis in the brain, which is closely associated with ferroptosis. In this study, the role and underlying mechanism of ferroptosis in PM2.5-induced neurotoxicity were investigated in mice, primary hippocampal neurons, and HT22 cells. Our findings demonstrated that exposure to PM2.5 could induce abnormal behaviors, neuroinflammation, and neuronal loss in the hippocampus of mice. These effects may be attributed to ferroptosis induced by PM2.5 exposure in hippocampal neurons. RNA-seq analysis revealed that the upregulation of iron metabolism-related protein Heme Oxygenase 1 (HO-1) and the activation of mitophagy might play key roles in PM2.5-induced ferroptosis in HT22 cells. Subsequent in vitro experiments showed that PM2.5 exposure significantly upregulated HO-1 in primary hippocampal neurons and HT22 cells. Moreover, PM2.5 exposure activated mitophagy in HT22 cells, leading to the loss of mitochondrial membrane potential, alterations in the expression of autophagy-related proteins LC3, P62, and mTOR, as well as an increase in mitophagy-related protein PINK1 and PARKIN. As a heme-degradation enzyme, the upregulation of HO-1 promotes the release of excess iron, genetically inhibiting the upregulation of HO-1 in HT22 cells could prevent both PM2.5-induced mitophagy and ferroptosis. Furthermore, pharmacological inhibition of mitophagy in HT22 cells reduced levels of ferrous ions and lipid peroxides, thereby preventing ferroptosis. Collectively, this study demonstrates that HO-1 mediates PM2.5-induced mitophagy-dependent ferroptosis in hippocampal neurons, and inhibiting mitophagy or ferroptosis may be a key therapeutic target to ameliorate neurotoxicity following PM2.5 exposure.

BackgroundLower respiratory tract infections represent prevalent ailments. Nonetheless, current comprehension of the microbial ecosystems within the lower respiratory tract remains incomplete and necessitates further comprehensive assessment. Leveraging the advancements in metagenomic next-generation sequencing (mNGS) technology alongside the emergence of machine learning, it is now viable to compare the attributes of lower respiratory tract microbial communities among patients across diverse age groups, diseases, and infection types.MethodWe collected bronchoalveolar lavage fluid samples from 138 patients diagnosed with lower respiratory tract infections and conducted mNGS to characterize the lung microbiota. Employing various machine learning algorithms, we investigated the correlation of key bacteria in patients with concurrent bronchiectasis and developed a predictive model for hospitalization duration based on these identified key bacteria.ResultWe observed variations in microbial communities across different age groups, diseases, and infection types. In the elderly group, Pseudomonas aeruginosa exhibited the highest relative abundance, followed by Corynebacterium striatum and Acinetobacter baumannii. Methylobacterium and Prevotella emerged as the dominant genera at the genus level in the younger group, while Mycobacterium tuberculosis and Haemophilus influenzae were prevalent species. Within the bronchiectasis group, dominant bacteria included Pseudomonas aeruginosa, Haemophilus influenzae, and Klebsiella pneumoniae. Significant differences in the presence of Pseudomonas phage JBD93 were noted between the bronchiectasis group and the control group. In the group with concomitant fungal infections, the most abundant genera were Acinetobacter and Pseudomonas, with Acinetobacter baumannii and Pseudomonas aeruginosa as the predominant species. Notable differences were observed in the presence of Human gammaherpesvirus 4, Human betaherpesvirus 5, Candida albicans, Aspergillus oryzae, and Aspergillus fumigatus between the group with concomitant fungal infections and the bacterial group. Machine learning algorithms were utilized to select bacteria and clinical indicators associated with hospitalization duration, confirming the excellent performance of bacteria in predicting hospitalization time.ConclusionOur study provided a comprehensive description of the microbial characteristics among patients with lower respiratory tract infections, offering insights from various perspectives. Additionally, we investigated the advanced predictive capability of microbial community features in determining the hospitalization duration of these patients.

Summary: Background: GST-HG171 is a potent, broad-spectrum, orally bioavailable small-molecule 3C like protease inhibitor that has demonstrated greater potency and efficacy compared to Nirmatrelvir in pre-clinical studies. We aimed to evaluate the efficacy and safety of orally administered GST-HG171 plus Ritonavir in patients with coronavirus disease 2019 (COVID-19) infected with emerging XBB and non-XBB variants. Methods: This randomised, double-blind, placebo-controlled phase 2/3 trial was conducted in 47 sites in China among adult patients with mild-to-moderate COVID-19 with symptoms onset ≤72 h. Eligible patients were randomised 1:1 to receive GST-HG171 (150 mg) plus Ritonavir (100 mg) or corresponding placebo tablets twice daily for 5 days, with stratification factors including the risk level of disease progression and vaccination status. The primary efficacy endpoint was time to sustained recovery of clinical symptoms within 28 days, defined as a score of 0 for 11 COVID-19-related target symptoms for 2 consecutive days, assessed in the modified intention-to-treat (mITT) population. This trial was registered at ClinicalTrials.gov (NCT05656443) and Chinese Clinical Trial Registry (ChiCTR2200067088). Findings: Between Dec 19, 2022, and May 4, 2023, 1525 patients were screened. Among 1246 patients who underwent randomisation, most completed basic (21.2%) or booster (74.9%) COVID-19 immunization, and most had a low risk of disease progression at baseline. 610 of 617 who received GST-HG171 plus Ritonavir and 603 of 610 who received placebo were included in the mITT population. Patients who received GST-HG171 plus Ritonavir showed shortened median time to sustained recovery of clinical symptoms compared to the placebo group (13.0 days [95.45% confidence interval 12.0–15.0] vs. 15.0 days [14.0–15.0], P = 0.031). Consistent results were observed in both SARS-CoV-2 XBB (45.7%, 481/1053 of mITT population) and non-XBB variants (54.3%, 572/1053 of mITT population) subgroups. Incidence of adverse events was similar in the GST-HG171 plus Ritonavir (320/617, 51.9%) and placebo group (298/610, 48.9%). The most common adverse events in both placebo and treatment groups were hypertriglyceridaemia (10.0% vs. 14.7%). No deaths occurred. Interpretation: Treatment with GST-HG171 plus Ritonavir has demonstrated benefits in symptom recovery and viral clearance among low-risk vaccinated adult patients with COVID-19, without apparent safety concerns. As most patients were treated within 2 days after symptom onset in our study, confirming the potential benefits of symptom recovery for patients with a longer duration between symptom onset and treatment initiation will require real-world studies. Funding: Fujian Akeylink Biotechnology Co., Ltd.

The secondary disasters such as flash floods, landslides and debris flows induced by sudden mountain rainstorm are major natural disasters in mountain areas of China. In this paper, the statistical characteristics of sudden mountain rainstorm events in Sichuan Province are analyzed by using the 10 year hourly precipitation data of national stations from 2008 to 2017. The results are as following: (1) During the 10 years from 2008 to 2017, there were 979 sudden mountain rainstorm events in Sichuan Province, with an average of 98 events per year. More than 5 sudden rainstorm events occurred in most areas. Sudden rainstorm events mainly occur in the Sichuan Basin and its eastern and southern mountainous areas, and the frequency of sudden rainstorm events in the western mountainous areas is far higher than that in the eastern mountainous areas, which indicates that it is closely related to the terrain. (2) The sudden rainstorm events increased from April, increased by leaps and bounds from June to July, and gradually decreased after July. The sudden rainstorm events at night is more than that in the daytime. The high-frequency distribution of sudden rainstorm events starts at 16:00 pm. in the western mountainous area of Sichuan Province, and turns to the highest in the eastern mountainous area at midnight, which shows that there is a process of development and propagation of heavy rainfall from west to east. (3) The duration of mountain sudden rainstorm events is mostly concentrated in 3~12h, and the average duration is longer in June, July and September, but shorter in May and August. (4) The annual average rainfall of sudden mountain rainstorm events ranges from 80 mm to 120 mm. The accumulated rainfall is the largest in July, followed by August, and the smallest in May and September. In 2015, the frequency of sudden mountain rainstorm events was the least, but the annual average accumulated rainfall was the most, indicating that the intensity of sudden rainstorm was the largest in 2015.

Abstract Unavoidable nonmetallic inclusions generated in the steelmaking process are fatal defects that often cause serious corrosion failure of steel, leading to catastrophic accidents and huge economic losses. Over the past decades, extensive efforts have been made to address this difficult issue, but none of them have succeeded. Here, we propose a strategy of wrapping deleterious inclusions with corrosion-resistant niobium armour (Z phase). After systematic theoretical screening, we introduce minor Nb into duplex stainless steels (DSSs) to form inclusion@Z core-shell structures, thus isolating the inclusions from corrosive environments. Additionally, both the Z phase and its surrounding matrix possess excellent corrosion resistance. Thus, this strategy effectively prevents corrosion caused by inclusions, thereby doubly improving the corrosion resistance of DSSs. Our strategy overcomes the long-standing problem of “corrosion failure caused by inclusions”, and it is verified as a universal technique in a series of DSSs and industrial production.

Abstract Background Pneumocystis pneumonia (PCP) is a life-threatening pulmonary fungal infection that predominantly affects immunocompromised individuals, including kidney transplant recipients. Recent years have witnessed a rising incidence of PCP in this vulnerable population, leading to graft loss and increased mortality. Immunosuppression, which is essential in transplant recipients, heightens susceptibility to viral and opportunistic infections, magnifying the clinical challenge. Concurrently, the global impact of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been profound. Kidney transplant recipients have faced severe outcomes when infected with SARS-CoV-2, often requiring intensive care. Co-infection with COVID-19 and PCP in this context represents a complex clinical scenario that requires precise management strategies, involving a delicate balance between immunosuppression and immune activation. Although there have been case reports on management of COVID-19 and PCP in kidney transplant recipients, guidance on how to tackle these infections when they occur concurrently remains limited. Case presentations We have encountered four kidney transplant recipients with concurrent COVID-19 and PCP infection. These patients received comprehensive treatment that included adjustment of their maintenance immunosuppressive regimen, anti-pneumocystis therapy, treatment for COVID-19 and other infections, and symptomatic and supportive care. After this multifaceted treatment strategy, all of these patients improved significantly and had favorable outcomes. Conclusions We have successfully managed four kidney transplant recipients co-infected with COVID-19 and PCP. While PCP is a known complication of immunosuppressive therapy, its incidence in patients with COVID-19 highlights the complexity of dual infections. Our findings suggest that tailored immunosuppressive regimens, coupled with antiviral and antimicrobial therapies, can lead to clinical improvement in such cases. Further research is needed to refine risk assessment and therapeutic strategies, which will ultimately enhance the care of this vulnerable population.

Abstract Gamma radiation is progressively emerging as an effective method to enhance the sterilization efficiency of medical plastics including Polyvinyl chloride (PVC). The parameters of the radiation facility will affect the efficiency of radiation sterilization. To investigate these effects, we simulate the gamma radiation sterilization performance of PVC material sample using Monte Carlo Method. The simulation results indicated that compared with the sterilization time of 20–90 min from high-temperature steam sterilization of medical waste, by optimizing the parameters of the model radiation facility, the radiation sterilization time can be reduced to 6.61 min. The optimized model facility parameters are as follows: the gamma photon energy is 1.25 MeV, the model space is 300 × 300 × 300 cm3, the reflective layer material is concrete and its thickness is 8 cm, the PVC sample layer area is 100 × 100 cm2, the distance between the radiation source and the PVC sample layer is 150 cm, the energy deposition in the bottom layer of the PVC sample layer is 1.31315 × 10–6 MeV/g. This study offers a potentially feasible way for PVC sterilization, while also providing a crucial reference for the further promotion and application of radiation sterilization technology.

Background Acute pulmonary embolism (APE) is classified as a subset of diseases that are characterized by lung obstruction due to various types of emboli. Current clinical APE treatment using anticoagulants is frequently accompanied by high risk of bleeding complications. Recombinant hirudin (R-hirudin) has been found to have antithrombotic properties. However, the specific impact of R-hirudin on APE remains unknown. Methods Sprague-Dawley (SD) rats were randomly assigned to five groups, with thrombi injections to establish APE models. Control and APE group rats were subcutaneously injected with equal amounts of dimethyl sulfoxide (DMSO). The APE+R-hirudin low-dose, middle-dose, and high-dose groups received subcutaneous injections of hirudin at doses of 0.25 mg/kg, 0.5 mg/kg, and 1.0 mg/kg, respectively. Each group was subdivided into time points of 2 h, 6 h, 1 d, and 4 d, with five animals per point. Subsequently, all rats were euthanized, and serum and lung tissues were collected. Following the assessment of right ventricular pressure (RVP) and mean pulmonary artery pressure (mPAP), blood gas analysis, enzyme-linked immunosorbnent assay (ELISA), pulmonary artery vascular testing, hematoxylin-eosin (HE) staining, Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining, immunohistochemistry, and Western blot experiments were conducted. Results R-hirudin treatment caused a significant reduction of mPAP, RVP, and Malondialdehyde (MDA) content, as well as H2O2 and myeloperoxidase (MPO) activity, while increasing pressure of oxygen (PaO2) and Superoxide Dismutase (SOD) activity. R-hirudin also decreased wall area ratio and wall thickness to diameter ratio in APE rat pulmonary arteries. Serum levels of endothelin-1 (ET-1) and thromboxaneB2 (TXB2) decreased, while prostaglandin (6-K-PGF1α) and NO levels increased. Moreover, R-hirudin ameliorated histopathological injuries and reduced apoptotic cells and Matrix metalloproteinase-9 (MMP9), vascular cell adhesion molecule-1 (VCAM-1), p-Extracellular signal-regulated kinase (ERK)1/2/ERK1/2, and p-P65/P65 expression in lung tissues. Conclusion R-hirudin attenuated pulmonary hypertension and thrombosis in APE rats, suggesting its potential as a novel treatment strategy for APE.

Background The purpose of the present study was to investigate the effect of erythropoietin (EPO) on lung ischemia-reperfusion injury (LIRI). Methods Sprague Dawley rats and BEAS-2B cells were employed to construct an ischemia-reperfusion (I/R)-induced model in vivo and in vitro, respectively. Afterward, I/R rats and tert-butyl hydroperoxide (TBHP)-induced cells were treated with different concentrations of EPO. Furthermore, 40 patients with LIRI and healthy controls were enrolled in the study. Results It was observed that lung tissue damage, cell apoptosis and the expression of BAX and caspase-3 were higher in the LIRI model in vivo and in vitro than in the control group, nevertheless, the Bcl-2, FGF23 and FGFR4 expression level was lower than in the control group. EPO administration significantly reduced lung tissue damage and cell apoptosis while also up-regulating the expression of FGF23 and FGFR4. Rescue experiments indicated that EPO exerted a protective role associated with the FGF23/FGFR4/p-ERK1/2 signal pathway. Notably, the expression of serum EPO, FGF23, FGFR4 and Bcl-2 was decreased in patients with LIRI, while the expression of caspase-3 and BAX was higher. Conclusion EPO could effectively improve LIRI, which might be related to the activation of the FGF23/FGFR4/p-ERK1/2 signaling pathway.

In order to comprehend the underlying mechanisms contributing to the development and exacerbation of asthma resulting from exposure to fine particulate matter (PM2.5), we established an asthmatic model in fat mass and obesity-associated gene knockdown mice subjected to PM2.5 exposure. Histological analyses using hematoxylin-eosin (HE) and Periodic Acid-Schiff (PAS) staining revealed that the down-regulation of the fat mass and obesity-associated gene (Fto) expression significantly ameliorated the pathophysiological alterations observed in asthmatic mice exposed to PM2.5. Furthermore, the down-regulation of Fto gene expression effectively attenuated damage to the airway epithelial barrier. Additionally, employing in vivo and in vitro models, we elucidated that PM2.5 modulated FTO expression by inducing oxidative stress. Asthmatic mice exposed to PM2.5 exhibited elevated Fto expression, which correlated with increased levels of reactive oxygen species. Similarly, when cells were exposed to PM2.5, FTO expression was up-regulated in a ROS-dependent manner. Notably, the administration of N-acetyl cysteine successfully reversed the PM2.5-induced elevation in FTO expression. Concurrently, we performed transcriptome-wide Methylated RNA immunoprecipitation Sequencing (MeRIP-seq) analysis subsequent to PM2.5 exposure. Through the implementation of Gene Set Enrichment Analysis and m6A-IP-qPCR, we successfully identified inhibitor of nuclear factor kappa B kinase subunit beta (IKBKB) as a target gene regulated by FTO. Interestingly, exposure to PM2.5 led to increased expression of IKBKB, while m6A modification on IKBKB mRNA was reduced. Furthermore, our investigation revealed that PM2.5 also regulated IKBKB through oxidative stress. Significantly, the down-regulation of IKBKB effectively mitigated epithelial barrier damage in cells exposed to PM2.5 by modulating nuclear factor-kappa B (NF-κB) signaling. Importantly, we discovered that decreased m6A modification on IKBKB mRNA facilitated by FTO enhanced its stability, consequently resulting in up-regulation of IKBKB expression. Collectively, our findings propose a novel role for FTO in the regulation of IKBKB through m6A-dependent mRNA stability in the context of PM2.5-induced oxidative stress. Therefore, it is conceivable that the utilization of antioxidants or inhibition of FTO could represent potential therapeutic strategies for the management of asthma exacerbated by PM2.5 exposure.

The impact of high temperature environments on the physical and mechanical properties of rocks is a significant factor to consider. The investigation into the impact of elevated temperatures on the physical and mechanical characteristics of rocks holds great importance in the advancement and exploitation of deep-seated mineral reserves, as well as in ensuring the safety and stability of subterranean engineering projects. This study utilizes the state-of-the-art GCTS Mechanical Loading Test System to conduct uniaxial and triaxial compression tests on sandstone after thermal treatment from 25°C to 650°C. In addition, XRD, SEM and nuclear magnetic resonance experiments were carried out on the sandstone after thermal treatment. The aim of the experiments is to provide a quantitative characterization of mechanical properties and behaviors of the rock samples. The results show that the mass, density, and wave velocity of sandstone decrease with increasing temperature, while volume and porosity increase. The mass, volume, and rate of density change of sandstone exhibit a significant increase when subjected to temperatures above 500°C. The uniaxial compressive strength and elastic modulus exhibit an initial increase followed by a subsequent decrease as the temperature rises, with 300°C serving as the critical turning point. The axial peak strain and Poisson’s ratio increase with increasing temperature. The cohesion decreases with increasing temperature, while the internal friction angle increases. Additionally, it is observed that the rate of change for both properties exhibits an increase beyond the temperature threshold of 400°C.

Fibrotic hypersensitivity pneumonitis (FHP) is a fatal interstitial pulmonary disease with limited treatment options. Lung macrophages are a heterogeneous cell population that exhibit distinct subsets with divergent functions, playing pivotal roles in the progression of pulmonary fibrosis. However, the specific macrophage subpopulations and underlying mechanisms involved in the disease remain largely unexplored. In this study, a decision tree model showed that matrix metalloproteinase-14 (MMP14) had higher scores for important features in the up-regulated genes in macrophages from mice exposed to the Saccharopolyspora rectivirgula antigen (SR-Ag). Using single-cell RNA sequencing (scRNA-seq) analysis of hypersensitivity pneumonitis (HP) mice profiles, we identified MMP14high macrophage subcluster with a predominant M2 phenotype that exhibited higher activity in promoting fibroblast-to myofibroblast transition (FMT). We demonstrated that suppressing toll-like receptor 2 (TLR2) and nuclear factor kappa-B (NF-κB) could attenuate MMP14 expression and exosome secretion in macrophages stimulation with SR-Ag. The exosomes derived from MMP14-overexpressing macrophages were found to be more effective in regulating the transition of fibroblasts through exosomal MMP14. Importantly, it was observed that the transfer of MMP14-overexpressing macrophages into mice promoted lung inflammation and fibrosis induced by SR-Ag. NSC-405020 binding to the hemopexin domain (PEX) of MMP-14 ameliorated lung inflammation and fibrosis induced by SR-Ag in mice. Thus, MMP14-overexpressing macrophages may be an important mechanism contributing to the exacerbation of allergic reactions. Our results indicated that MMP14 in macrophages has the potential to be a therapeutic target for HP.

Background and objective Idiopathic pulmonary fibrosis (IPF) is an idiopathic chronic, progressive interstitial lung disease with a diagnosed median survival of 3-5 years. IPF is associated with an increased risk of lung cancer. Therefore, exploring the shared pathogenic genes and molecular pathways between IPF and lung adenocarcinoma (LUAD) holds significant importance for the development of novel therapeutic approaches and personalized precision treatment strategies for IPF combined with lung cancer. Methods Bioinformatics analysis was conducted using publicly available gene expression datasets of IPF and LUAD from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis was employed to identify common genes involved in the progression of both diseases, followed by functional enrichment analysis. Subsequently, additional datasets were used to pinpoint the core shared genes between the two diseases. The relationship between core shared genes and prognosis, as well as their expression patterns, clinical relevance, genetic characteristics, and immune-related functions in LUAD, were analyzed using The Cancer Genome Atlas (TCGA) database and single-cell RNA sequencing datasets. Finally, potential therapeutic drugs related to the identified genes were screened through drug databases. Results A total of 529 shared genes between IPF and LUAD were identified. Among them, SULF1 emerged as a core shared gene associated with poor prognosis. It exhibited significantly elevated expression levels in LUAD tissues, concomitant with high mutation rates, genomic heterogeneity, and an immunosuppressive microenvironment. Subsequent single-cell RNA-seq analysis revealed that the high expression of SULF1 primarily originated from tumor-associated fibroblasts. This study further demonstrated an association between SULF1 expression and tumor drug sensitivity, and it identified potential small-molecule drugs targeting SULF1 highly expressed fibroblasts. Conclusions This study identified a set of shared molecular pathways and core genes between IPF and LUAD. Notably, SULF1 may serve as a potential immune-related biomarker and therapeutic target for both diseases.

In order to probe into the value of exploration and utilization of Yingjiang uncultivated ancient tea resources, representative samples of spore tea from Camellia taliensis in Yingjiang county (spore white tea and spore black tea) were selected, and typical Yunnan samples (Yunnan white tea and Yunnan black tea golden bud) were taken as a control sample of them. At the same time, sensory evaluation and chemical composition test detection were used to compare the differences in taste chemical composition of the sample, and analyze the key taste components of the sample in combination with the method of taste activity value (TAV). The results showed that in sensory evaluation, spore white tea and spore black tea had a unique shape like a bamboo shoot, and their quality of taste was better than that of Yunnan white tea and Yunnan black tea golden bud. The test results of chemical composition showed that the content of chemical components in the taste of spore white tea was generally low and other components were significantly lower than that of Yunnan white tea, except for the content of soluble sugar as high as 9.45%, the content of taste's chemical components of spore black tea such as water extract, free amino acid, soluble sugar, sweet amino acid was high, all of which were significantly higher than that of Yunnan black tea golden bud, especially the content of soluble sugar which was up to 20.37%. While the content of tea polyphenols, caffeine, ester catechins, etc. was relatively low, in which the content of tea polyphenols was as low as 6.98%, showing that the ratio of tea polyphenols to amino acids was low and the ratio of soluble sugar to caffeine was high. Thus, the results were consistent with the sensory evaluation results. The results of TAV analysis showed that the contribution of the bitter and astringent chemical components including catechin components, caffeine and partial amino acids in the key components to spore white tea and spore black tea was lower than that of the control samples. In conclusion, the content of chemical components in the taste of Yingjiang spore tea was quite different from the control sample in Yunnan Province, and the quality of Yingjiang spore tea was excellent. What's more, the uncultivated ancient tea resources of Camellia taliensis had high value of exploration and utilization, especially suitable for making black tea.

With the application of modern coal mining technology and the fact that there are fewer and fewer high-quality coal seams, the quality enhancement and utilization of low-rank coal are gaining more and more attention. To solve the problems of high consumption of chemicals and low recovery of refined coal in the flotation separation process of low-rank coal, the long-flame coal from the Inner Mongolia Autonomous Region of China was selected as the research object, and the factors affecting the flotation process were analyzed and optimized by adopting the response surface method and establishing a regression model with high precision and reliability. The test results showed that the primary and secondary relationships of the factors on the fine coal yield were as follows: slurry concentration > frother dosage > collector dosage; and the primary and secondary relationships of the factors on the flotation refinement index were as follows: slurry concentration > collector dosage > frother dosage. The optimal conditions for flotation were 2453.09 g/t of collector, 795.84 g/t of frother, and 50.04 g/L of slurry concentration. Under these conditions, the fine coal yield was 51.51%, and the relative error of 53.71% was 4.27%. The flotation refinement index was 21.34%, and the relative error with the predicted value of 21.58% was 1.12%. The relative error of the experimental results was within a reasonable range, which indicated that the regression model obtained by the response surface method was highly reliable. The research results are of great significance to strengthen the comprehensive utilization of long-flame coal in full particle size and improve the economic benefits of coal enterprises.

The application of hexanitrohexaazaisowurtzitane (HNIW) as an oxidizer in solid propellants aligns with the pursuit of high-energy materials. However, the phase transformation behavior and high impact sensitivity of HNIW are its limitations. Due to the strong adhesion and mild synthesis conditions, polydopamine (PDA) has been employed to modify HNIW. However, the method suffers from a slow coating process and a non-ideal coating effect under short reaction time. Herein, oxygen-accelerated dopamine in situ polymerization coating method was developed. It was found that oxygen not only reduced the coating time but also contributed to forming a dense and uniform PDA layer. HNIW@PDA coated in oxygen for 6 h exhibited the most favorable performance, with a delay of 20.8 °C in the phase transition temperature and a reduction of 145.45% in the impact sensitivity. The -OH groups on the surface of PDA enhanced the interaction between HNIW and polymer binders, resulting in a 20.36% reduction in the dewetting percentage. The lower content of PDA in HNIW@PDA (1.17%) resulted in minimal variation in the heat of explosion for HNIW@PDA-based HTPB propellant (6287 kJ/kg) in comparison to HNIW-based HTPB propellant (6297 kJ/kg). Hence, HNIW@PDA-based propellants are expected to offer an alternative with promising safety and mechanical performance compared to existing HNIW-based propellants, thus facilitating the application of HNIW in high-energy propellants. This work presents a low-cost method for efficiently inhibiting the phase transformation of polycrystalline explosives and reducing the impact sensitivity. It also offers a potential approach to enhance the interfacial interaction between nitro-containing explosives and polymer binders.

Abstract Tumor-infiltrating immune cells and fibroblasts are significant components of the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC), and they participate in tumor progression as closely as tumor cells. However, the relationship between the features of the TME and patient outcomes and the interactions among TME components are still unclear. In this study, we evaluated the PDAC TME in terms of the quantity and location of cluster of differentiation (CD)4+ T cells, CD8+ T cells, macrophages, stromal maturity, and tumor-stroma ratio (TSR), as evaluated by immunohistochemical staining of serial whole-tissue sections from 116 patients with PDAC. The density of T cells and macrophages (mainly activated macrophages) was significantly higher at the invasive margins (IMs) than at the tumor center (TC). CD4+ T cells were significantly association with all the other tumor-associated immune cells (TAIs) including CD8, CD68 and CD206 positive cells. Tumors of the non-mature (intermediate and immature) stroma type harbored significantly more CD8+ T cells at the IMs and more CD68+ macrophages at the IMs and the TC. The density of CD4+, CD8+, and CD206+ cells at the TC; CD206+ cells at the IMs; and tumor-node-metastasis (TNM) staging were independent risk factors for patient outcomes, and the c-index of the risk nomogram for predicting the survival probability based on the TME features and TNM staging was 0.772 (95% confidence interval: 0.713–0.832). PDAC harbored a significantly immunosuppressive TME, of which the IMs were the hot zones for TAIs, while cells at the TC were more predictive of prognosis. Our results indicated that the model based on the features of the TME and TNM staging could predict patient outcomes.

Abstract Exercise has well-recognized beneficial effects on the whole body. Previous studies suggest that exercise could promote tissue regeneration and repair in various organs. In this review, we have summarized the major effects of exercise on tissue regeneration primarily mediated by stem cells and progenitor cells in skeletal muscle, nervous system, and vascular system. The protective function of exercise-induced stem cell activation under pathological conditions and aging in different organs have also been discussed in detail. Moreover, we have described the primary molecular mechanisms involved in exercise-induced tissue regeneration, including the roles of growth factors, signaling pathways, oxidative stress, metabolic factors, and non-coding RNAs. We have also summarized therapeutic approaches that target crucial signaling pathways and molecules responsible for exercise-induced tissue regeneration, such as IGF1, PI3K, and microRNAs. Collectively, the comprehensive understanding of exercise-induced tissue regeneration will facilitate the discovery of novel drug targets and therapeutic strategies.

Vibration data from mechanical equipment contain extensive information distributed across multiple dimensions. Single-scale analysis fails to comprehensively reflect its damage characteristics, thereby reducing fault diagnosis accuracy. This study proposes a novel signal vibration feature extraction method called hierarchical refined composite generalized multiscale fluctuation dispersion entropy (HRCGMFDE). This method simultaneously extracts fault information from both low-frequency and high-frequency components of the data, addressing the drawback of high-frequency information loss in refined composite generalized multiscale fluctuation dispersion entropy (RCMFDE). Comparative results on two simulated signals demonstrate the method’s advantages of high stability and more accurate complexity measurement. Furthermore, low-frequency and high-frequency components of the data are comprehensively extracted using dual-tree complex wavelet packet transform (DTCWPT), and high-dimensional features are downscaled using t-distributed stochastic neighbor embedding (t-SNE) to obtain low-dimensional sensitive fault features. Subsequently, a Random Forest (RF) classifier is employed for fault identification. Finally, the effectiveness of the proposed method is validated using three typical mechanical datasets. Results confirm the method’s capability to effectively determine the fault states of bearings, gearboxes, and centrifugal pumps, showcasing significant advantages over comparative methods.

Exercise can stimulate physiological cardiac growth and provide cardioprotection effect in ischemia/reperfusion (I/R) injury. MiR-210 is regulated in the adaptation process induced by exercise; however, its impact on exercise-induced physiological cardiac growth and its contribution to exercise-driven cardioprotection remain unclear. We investigated the role and mechanism of miR-210 in exercise-induced physiological cardiac growth and explored whether miR-210 contributes to exercise-induced protection in alleviating I/R injury. Here, we first observed that regular swimming exercise can markedly increase miR-210 levels in the heart and blood samples of rats and mice. Circulating miR-210 levels were also elevated after a programmed cardiac rehabilitation in patients that were diagnosed of coronary heart diseases. In 8-week swimming model in wild-type (WT) and miR-210 knockout (KO) rats, we demonstrated that miR-210 was not integral for exercise-induced cardiac hypertrophy but it did influence cardiomyocyte proliferative activity. In neonatal rat cardiomyocytes, miR-210 promoted cell proliferation and suppressed apoptosis while not altering cell size. Additionally, miR-210 promoted cardiomyocyte proliferation and survival in human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and AC16 cell line, indicating its functional roles in human cardiomyocytes. We further identified miR-210 target genes, cyclin-dependent kinase 10 (CDK10) and ephrin-A3 (EFNA3), that regulate cardiomyocyte proliferation and apoptosis. Finally, miR-210 KO and WT rats were subjected to swimming exercise followed by I/R injury. We demonstrated that miR-210 crucially contributed to exercise-driven cardioprotection against I/R injury. In summary, this study elucidates the role of miR-210, an exercise-responsive miRNA, in promoting the proliferative activity of cardiomyocytes during physiological cardiac growth. Furthermore, miR-210 plays an essential role in mediating the protective effects of exercise against cardiac I/R injury. Our findings suggest exercise as a potent nonpharmaceutical intervention for inducing miR-210, which can alleviate I/R injury and promote cardioprotection.

AbstractPurpose Few risk-forecasting models of allergic rhinitis (AR) exist that may aid AR pre-exposure prophylaxis (PrEP) in clinical practice. Therefore, this study aimed to develop and validate an effective clinical model for identifying candidates for AR PrEP using a routine medical questionnaire.Methods This study was conducted in 10 Chinese provinces with 13 medical centers (n = 877) between 2019 and 2021. Clinical characteristics and exposure history were collected via face-to-face interviews. Well-trained physicians diagnosed patients with AR based on skin prick test results and clinical performance. The least absolute shrinkage and selection operator model was used to identify potential risk factors for AR, and the logistic regression model was used to construct the risk-forecasting model. Predictive power and model reliability were assessed using area under the receiver operating characteristic curve and calibration curves, respectively.Results This study diagnosed 625 patients with AR who had positive responses to at least one indoor or outdoor allergen and 460 to at least one outdoor pollen allergen. Two nomograms were established to identify two types of AR with various sensitization patterns. Both models had an area under curve of approximately 0.7 in the development and internal validation datasets. Additionally, our findings found good agreement for the calibration curves of both models.Conclusion Early identification of candidates for AR PrEP using routine medical information may improve the deployment of limited resources and effective health management. Our models showed good performance in predicting AR; therefore, they can serve as potential automatic screening tools to identify AR PrEP candidates.

Muscle atrophy is debilitating and can be induced by several stressors. Unfortunately, there are no effective pharmacological treatment until now. MicroRNA (miR)-29b is an important target that we identified to be commonly involved in multiple types of muscle atrophy. Although sequence-specific inhibition of miR-29b has been developed, in this study, we report a novel small-molecule miR-29b inhibitor that targets miR-29b hairpin precursor (pre-miR-29b) (Targapremir-29b-066 [TGP-29b-066]) considering both its three-dimensional structure and the thermodynamics of interaction between pre-miR-29b and the small molecule. This novel small-molecule inhibitor has been demonstrated to attenuate muscle atrophy induced by angiotensin II (Ang II), dexamethasone (Dex), and tumor necrosis factor α (TNF-α) in C2C12 myotubes, as evidenced by increase in the diameter of myotube and decrease in the expression of Atrogin-1 and MuRF-1. Moreover, it can also attenuate Ang II-induced muscle atrophy in mice, as evidenced by a similar increase in the diameter of myotube, reduced Atrogin-1 and MuRF-1 expression, AKT-FOXO3A-mTOR signaling activation, and decreased apoptosis and autophagy. In summary, we experimentally identified and demonstrated a novel small-molecule inhibitor of miR-29b that could act as a potential therapeutic agent for muscle atrophy.

There are sometimes great differences in the raindrop spectrum characteristics between short-term heavy rain (SHR) and persistent heavy rain (PHR) due to the different of cold cloud and warm cloud processes. Analyzing the difference of raindrop spectrum characteristics between SHR and PHR is helpful to understand the microphysical characteristics of the different types of heavy precipitation, which can play an important role in improving the estimation accuracy of radar quantitative precipitation. Taking an event with SHR and PHR processes caused by the Southwest China vortex in June 2018 in Hubei as an example, based on the observations from the automatic weather stations, CINRADA/SA Doppler weather radar data, raindrop spectrum from DSG5 precipitation phenomenon instruments, and the ERA5 reanalysis data, we comparatively analyzed the raindrop spectrum characteristics between SHR and PHR, and discussed their difference in the radar reflectivity (Z)-rainfall (R) relationship (Z=aRb) by fitting analysis. Results are as follows. (1) In the SHR process of this event, the average number concentration (ND) in the each particle size (D) is high, and the particle size is large for the convective cloud precipitation, which is related to the active ice phase process in the internal and the coalescence and collision-breakup process of raindrops in the warm cloud layer. While in the PHR process of this event, the ND of small particle size (D < 2mm) is high but the ND of medium and large particle size is low for the stratiform cloud precipitation. (2) Distribution of the normalized Gamma spectral intercept parameter (lgNw) and the mass weighted average diameter (Dm) shows that the SHR process has a wider raindrop spectrum, larger Dm and smaller lgNw, and the slope of separation line of convective-stratiform cloud precipitation is smaller. (3) The Z-R fitting formulas for the convective cloud precipitation in the SHR and PHR processes are Z=183.33 R1.56 and Z=169.74 R1.49, respectively. When the rain intensity (R) is greater than 60 mm·h-1, compared with the typical Z-R fitting formula (Z=300R1.40) for Doppler weather radar, the Z-R fitting formula (Z=428.38R1.37) for the convective cloud precipitation in the SHR process have a similar b value but a larger a value. If given Z, the R estimated by the Z-R fitting formula of SHR is weaker than that of PHR, which is caused by the existence of a small number of large particles.

Abstract Neonatal mouse heart can regenerate after left ventricle (LV) apical resection (AR). Since current AR rodent method is accomplished by resecting LV apex until exposure of LV chamber, it is relatively difficult to operate reproducibly. We aimed to develop a modified AR method with high accuracy and reproducibility and to investigate whether cardiac regenerative capacity could be replicated in neonatal rats. For 15% AR of whole heart weight in 1-day-old (P1) neonatal mice, a modified 10 μL pipette tip cut to 0.48 mm in internal diameter was connected to a vacuum pump working at 0.06 ± 0.005 MPa and gently kept in touch with LV apex for nearly but no more than 12 s. LV apex was resected by a single incision adjacent to the pipette tip. The modified AR method in P1 mice achieved cardiac structural and functional recovery at 21 days post resection (dpr). Data from different operators showed smaller variation of resected LV apex and higher reproducibility using the modified AR method. Furthermore, we showed that 5% AR of whole heart weight in P1 neonatal rats using a modified 200 μL pipette tip cut to 0.63 mm in internal diameter led to complete regeneration of LV apex and full preservation of cardiac function at 42 dpr. In conclusion, the modified AR rodent model leads to accurate resection of LV apex with high homogeneity and reproducibility and it is practically convenient for the study of structural, functional, and molecular mechanisms of cardiac regeneration in both neonatal mice and rats.

Glycidyl azide polymer (GAP)-based polyurethane is an ideal elastomeric matrix for high-energy, low-smoke, and insensitive solid propellants. As the skeleton structure of GAP propellants, changes in the structure and properties of GAP elastomers during aging lead to the deterioration of propellant performance (especially in relation to mechanical properties), which causes safety risks. A high-temperature-accelerated aging experiment (70 °C) on a GAP elastomer was conducted. The evolution of the microstructure of the GAP elastomer system was analyzed by Fourier-transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (NMR), and variations in the macroscopic properties were analyzed by the hardness test and the uniaxial tensile test. The experimental results showed that thermal aging of the GAP elastomer is a coupled process of multiple chemical reactions. The azide groups, urethane groups, and ether bonds were the weak links in the network structure, breaking during the aging process, and the crosslinking density rose and then decreased. Macroscopic properties also showed segmented changes. The aging process was divided into three stages: post-curing (stage one); when the crosslinked network began to break (stage two), and when the crosslinked network was destroyed (stage three). Changes in the microstructure and macroscopic properties were consistent. This work is of great significance for exploring the aging mechanism of GAP propellants and extending their storage life.

In this paper, by treating the cosmological constant as a thermodynamic pressure, we study the thermodynamics and phase transitions of the dyonic AdS black holes in Gauss-Bonnet-Scalar gravity, where the conformal scalar field is considered. In a more general extended phase space, we first verified the first law of black hole thermodynamics, and find that it is always true. Meanwhile, the corresponding Smarr relation is also obtained. Then, we found that this black hole exhibits interesting critical behaviors in six dimensions, i.e., two swallowtails can be observed simultaneously. Interestingly, in a specific parameter space, we observed the small/intermediate/large black hole phase transitions, with the triple point naturally appearing. Additionally, the small/large black hole phase transition, similar to the liquid/gas phase transition of the van der Waals fluids, can also be found in other parameter regions. Moreover, we note that the novel phase structure composed of two separate coexistence curves discovered in the dyonic AdS black holes in Einstein-Born-Infeld gravity disappears in Gauss-Bonnet-Scalar gravity. This suggests that this novel phase structure may be related to gravity theory, and importantly, it is generally observed that the triple point is a universal property of dyonic AdS black holes. On the other hand, we calculated the critical exponents near the critical points and found that they share the same values as in mean field theory. Finally, it is true that these results will provide some deep insights into the interesting thermodynamic properties of the dyonic AdS black holes in the background of conformal scalar fields.

Mango fruits are susceptible to diseases, such as anthracnose, during fruit development, leading to yield reduction. Epicuticular wax is closely related to resistance of plants to pathogenic bacterial invasion. In this study, the effect of mango fruit epicuticular wax on the invasion of Colletotrichum gloeosporioides was investigated, followed by to understand the changes of wax chemical composition and crystal morphology during mango fruit development using GC-MS and SEM. Results showed that the epicuticular wax of mango fruits can prevent the invasion of C. gloeosporioides, and ‘Renong’ showed the strongest resistance to C. gloeosporioides. The wax content of four mango varieties first increased and then decreased from 40 days after full bloom (DAFB) to 120 DAFB. In addition, 95 compounds were detected in the epicuticular wax of the four mango varieties at five developmental periods, in which primary alcohols, terpenoids and esters were the main wax chemical composition. Furthermore, the surface wax structure of mango fruit changed dynamically during fruit development, and irregular platelet-like crystals were the main wax structure. The present study showed the changes of wax content, chemical composition and crystal morphology during mango fruit development, and the special terpenoids (squalene, farnesyl acetate and farnesol) and dense crystal structure in the epicuticular wax of ‘Renong’ fruit may be the main reason for its stronger resistance to C. gloeosporioides than other varieties. Therefore, these results provide a reference for the follow-up study of mango fruit epicuticular wax synthesis mechanism and breeding.

A good safety and immunogenicity profile was reported in Phase I and II clinical trials of inactivated SARS-CoV-2 vaccines. Here, we report two cases associated with vaccine-associated adverse events, including one patient with fever and another with anaphylactic shock resulting from inactivated SARS-CoV-2 vaccination. Cell sub-types and the importance of genetic characteristics were assessed using single-cell mRNA sequencing and machine learning. Overall, the patient with fever showed a significant increase in the numbers of cytotoxic CD8 T cells and MKI67high CD8 T cells. A potential concurrent infection with the Epstein–Barr virus enhanced interferon type I responses to vaccination against the virus. STAT1, E2F1, YBX1, and E2F7 played a key role in the transcription regulation of MKI67high CD8 T cells. In contrast, the patient with allergic shock displayed predominant increases in the numbers of S100A9high monocytes, activated CD4 T cells, and PPBPhigh megakaryocytes. The decision tree showed that LYZ and S100A8 in S100A9high monocytes contributed to the degranulation of neutrophils and activation of neutrophils involved in allergic shock. PPBP and PF4 were major contributors to platelet degranulation. These findings highlight the diversity of adverse reactions following inactivated SARS-CoV-2 vaccination and show the emerging role of cellular subtypes and central genes in vaccine-associated adverse reactions.

Background Infertility is recognized as a common and worrisome problem of human reproduction worldwide. Based on previous studies, male factors account for about half of all infertility cases. Exposure to environmental toxicants is an important contributor to male infertility. Bisphenol A (BPA) is the most prominent toxic environmental contaminant worldwide affecting the male reproductive system. BPA can impair the function of the Golgi apparatus which is important in spermatogenesis. GGA1 is known as Golgi-localized, gamma adaptin ear-containing, ARF-binding protein 1. Previously, it has been shown that GGA1 is associated with spermatogenesis in Drosophila, however, its function in mammalian spermatogenesis remains unclear. Methods Gga1 knockout mice were generated using the CRISPR/Cas9 system. Gga1-/- male mice and wild-type littermates received intraperitoneal (i.p.) injections of BPA (40 µg/kg) once daily for 2 weeks. Histological and immunofluorescence staining were performed to analyze the phenotypes of these mice. Results Male mice lacking Gga1 had normal fertility without any obvious defects in spermatogenesis, sperm count and sperm morphology. Gga1 ablation led to infertility in male mice exposed to BPA, along with a significant reduction in sperm count, sperm motility and the percentage of normal sperm. Histological analysis of the seminiferous epithelium showed that spermatogenesis was severely disorganized, while apoptotic germ cells were significantly increased in the Gga1 null mice exposed to BPA. Our findings suggest that Gga1 protects spermatogenesis against damage induced by environmental pollutants.

Exercise is a vital component in maintaining optimal health and serves as a prospective therapeutic intervention for various diseases. The human microbiome, comprised of trillions of microorganisms, plays a crucial role in overall health. Given the advancements in microbiome research, substantial databases have been created to decipher the functionality and mechanisms of the microbiome in health and disease contexts. This review presents an initial overview of microbiomics development and related databases, followed by an in-depth description of the multi-omics technologies for microbiome. It subsequently synthesizes the research pertaining to exercise-induced modifications of the microbiome and diseases that impact the microbiome. Finally, it highlights the potential therapeutic implications of an exercise-modulated microbiome in intestinal disease, obesity and diabetes, cardiovascular disease, and immune/inflammation-related diseases.

Exercise has long been known for its active role in improving physical fitness and sustaining health. Regular moderate-intensity exercise improves all aspects of human health and is widely accepted as a preventative and therapeutic strategy for various diseases. It is well-documented that exercise maintains and restores homeostasis at the organismal, tissue, cellular, and molecular levels to stimulate positive physiological adaptations that consequently protect against various pathological conditions. Here we mainly summarize how moderate-intensity exercise affects the major hallmarks of health, including the integrity of barriers, containment of local perturbations, recycling and turnover, integration of circuitries, rhythmic oscillations, homeostatic resilience, hormetic regulation, as well as repair and regeneration. Furthermore, we summarize the current understanding of the mechanisms responsible for beneficial adaptations in response to exercise. This review aimed at providing a comprehensive summary of the vital biological mechanisms through which moderate-intensity exercise maintains health and opens a window for its application in other health interventions. We hope that continuing investigation in this field will further increase our understanding of the processes involved in the positive role of moderate-intensity exercise and thus get us closer to the identification of new therapeutics that improve quality of life.

The benefit of regular exercise on the heart has been well documented but the role of RNA m6A modification in exercise-induced cardiac remodelling remains largely unknown. In this study, the authors report that METTL14 plays an important role in RNA m6A modification in exercise-induced physiological cardiac hypertrophy.

Abstract Exercise training has been widely recognized as a healthy lifestyle as well as an effective non-drug therapeutic strategy for cardiovascular diseases (CVD). Functional and mechanistic studies that employ animal exercise models as well as observational and interventional cohort studies with human participants, have contributed considerably in delineating the essential signaling pathways by which exercise promotes cardiovascular fitness and health. First, this review summarizes the beneficial impact of exercise on multiple aspects of cardiovascular health. We then discuss in detail the signaling pathways mediating exercise’s benefits for cardiovascular health. The exercise-regulated signaling cascades have been shown to confer myocardial protection and drive systemic adaptations. The signaling molecules that are necessary for exercise-induced physiological cardiac hypertrophy have the potential to attenuate myocardial injury and reverse cardiac remodeling. Exercise-regulated noncoding RNAs and their associated signaling pathways are also discussed in detail for their roles and mechanisms in exercise-induced cardioprotective effects. Moreover, we address the exercise-mediated signaling pathways and molecules that can serve as potential therapeutic targets ranging from pharmacological approaches to gene therapies in CVD. We also discuss multiple factors that influence exercise’s effect and highlight the importance and need for further investigations regarding the exercise-regulated molecules as therapeutic targets and biomarkers for CVD as well as the cross talk between the heart and other tissues or organs during exercise. We conclude that a deep understanding of the signaling pathways involved in exercise’s benefits for cardiovascular health will undoubtedly contribute to the identification and development of novel therapeutic targets and strategies for CVD.

Based on the precipitation observations collected from the stations and the ERA5 analysis data, the moisture flux and budget of a rainstorm event that occurred in Jiangxia, Wuhan during the Meiyu period in 2020 were estimated. In addition, the Lagrangian hybrid single-particle orbit model (HYSPLIT4) is used to quantitatively analyze the contributions of various sources to the precipitation process during the event. The results are as follows. (1) The synoptic condition and its stability led to this rainstorm event and its maintenance. (2) The moisture was mainly transported from the South and West. It is the key for this torrential rainstorm event that the moisture was transported and concentrated through the Indian summer monsoon circulation at the lower latitude and the southerly flow surround the Western Pacific Subtropical High. In addition, the southerly inflow of moisture played an important role in the moisture budget of this rainstorm. (3) The main moisture sources of this rainstorm events were identified as the Indian Ocean, the Bay of Bengal-South China Sea, and the western Pacific, which accounted for 24%, 41%, and 34% of the total moisture supply, respectively. (4) The southern flow was the major channel for the moisture transport at 925 hPa, which mainly originated from the western Pacific and the South China Sea, while the southwestern flow was the major channel for the moisture transport at 850 hPa, which mainly originated from the Indian Ocean and the Bay of Bengal.

Abstract Renal fibrosis is a common consequence of various progressive nephropathies, including obstructive nephropathy, and ultimately leads to kidney failure. Infiltration of inflammatory cells is a prominent feature of renal injury after draining blockages from the kidney, and correlates closely with the development of renal fibrosis. However, the underlying molecular mechanism behind the promotion of renal fibrosis by inflammatory cells remains unclear. Herein, we showed that unilateral ureteral obstruction (UUO) induced Gasdermin D (GSDMD) activation in neutrophils, abundant neutrophil extracellular traps (NETs) formation and macrophage-to-myofibroblast transition (MMT) characterized by α-smooth muscle actin (α-SMA) expression in macrophages. Gsdmd deletion significantly reduced infiltration of inflammatory cells in the kidneys and inhibited NETs formation, MMT and thereby renal fibrosis. Chimera studies confirmed that Gsdmd deletion in bone marrow-derived cells, instead of renal parenchymal cells, provided protection against renal fibrosis. Further, specific deletion of Gsdmd in neutrophils instead of macrophages protected the kidney from undergoing fibrosis after UUO. Single-cell RNA sequencing identified robust crosstalk between neutrophils and macrophages. In vitro, GSDMD-dependent NETs triggered p65 translocation to the nucleus, which boosted the production of inflammatory cytokines and α-SMA expression in macrophages by activating TGF-β1/Smad pathway. In addition, we demonstrated that caspase-11, that could cleave GSDMD, was required for NETs formation and renal fibrosis after UUO. Collectively, our findings demonstrate that caspase-11/GSDMD-dependent NETs promote renal fibrosis by facilitating inflammation and MMT, therefore highlighting the role and mechanisms of NETs in renal fibrosis.