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BackgroundThe novel coronavirus SARS-CoV-2 caused the global COVID-19 pandemic. Emerging reports support lower mortality and reduced case numbers in highland areas; however, comparative studies on the cumulative impact of environmental factors and viral genetic diversity on COVID-19 infection rates have not been performed to date. ObjectiveThe aims of this study were to determine the difference in COVID-19 infection rates between high and low altitudes, and to explore whether the difference in the pandemic trend in the high-altitude region of China compared to that of the lowlands is influenced by environmental factors, population density, and biological mechanisms. MethodsWe examined the correlation between population density and COVID-19 cases through linear regression. A zero-shot model was applied to identify possible factors correlated to COVID-19 infection. We further analyzed the correlation of meteorological and air quality factors with infection cases using the Spearman correlation coefficient. Mixed-effects multiple linear regression was applied to evaluate the associations between selected factors and COVID-19 cases adjusting for covariates. Lastly, the relationship between environmental factors and mutation frequency was evaluated using the same correlation techniques mentioned above. ResultsAmong the 24,826 confirmed COVID-19 cases reported from 40 cities in China from January 23, 2020, to July 7, 2022, 98.4% (n=24,430) were found in the lowlands. Population density was positively correlated with COVID-19 cases in all regions (ρ=0.641, P=.003). In high-altitude areas, the number of COVID-19 cases was negatively associated with temperature, sunlight hours, and UV index (P=.003, P=.001, and P=.009, respectively) and was positively associated with wind speed (ρ=0.388, P0.1). Key nonsynonymous mutations showed positive correlations with altitude, wind speed, and air pressure and showed negative correlations with temperature, UV index, and sunlight hours. ConclusionsBy comparison with the lowlands, the number of confirmed COVID-19 cases was substantially lower in high-altitude regions of China, and the population density, temperature, sunlight hours, UV index, wind speed, PM2.5, and CO influenced the cumulative pandemic trend in the highlands. The identified influence of environmental factors on SARS-CoV-2 sequence variants adds knowledge of the impact of altitude on COVID-19 infection, offering novel suggestions for preventive intervention.

BackgroundHigh-altitude pulmonary hypertension (HAPH) is a common disease in regions of high altitude where performing right heart catheterization (RHC) is challenging. The development of a diagnostic scoring system is crucial for effective disease screening.MethodsA total of 148 individuals were included in a retrospective analysis, and an additional 42 residents were prospectively enrolled. We conducted a multivariable analysis to identify independent predictors of HAPH. Subsequently, we devised a prediction score based on the retrospective training set to anticipate the occurrence and severity of HAPH. This scoring system was further subjected to validation in the prospective cohort, in which all participants underwent RHC.ResultsThis scoring system, referred to as the GENTH score model (Glycated hemoglobin [OR = 4.5], Echocardiography sign [OR = 9.1], New York Heart Association-functional class [OR = 12.5], Total bilirubin [OR = 3.3], and Hematocrit [OR = 3.6]), incorporated five independent risk factors and demonstrated strong predictive accuracy. In the training set, the area under the curve (AUC) values for predicting the occurrence and severity of HAPH were 0.851 and 0.832, respectively, while in the validation set, they were 0.841 and 0.893. In the validation set, GENTH score model cutoff values of ≤18 or >18 points were established for excluding or confirming HAPH, and a threshold of >30 points indicated severe HAPH.ConclusionsThe GENTH score model, combining laboratory and echocardiography indicators, represents an effective tool for distinguishing potential HAPH patients and identifying those with severe HAPH. This scoring system improves the clinical screening of HAPH diseases and offers valuable insights into disease diagnosis and management.

Objective To develop the first prediction model based on the common clinical symptoms of high-altitude pulmonary edema (HAPE), enabling early identification and an easy-to-execute self-risk prediction tool.Methods A total of 614 patients who consulted People’s Hospital of Tibet Autonomous Region between January 2014 and April 2022 were enrolled. Out of those, 508 patients (416 males and 92 females) were diagnosed with HAPE and 106 were patients without HAPE (33 females and 72 males). They were randomly distributed into training (n=431) and validation (n=182) groups. Univariate and multivariate analysis were used to screen predictors of HAPE selected from the 36 predictors; nomograms were established based on the results of multivariate analysis. The receiver operating characteristic curve (ROC) was developed to obtain the area under the ROC curve (AUC) of the predictive model, and its predictive power was further evaluated by calibrating the curve, while the Decision Curve Analysis (DCA) was developed to evaluate the clinical applicability of the model, which was visualised by nomogram.Results All six predictors were significantly associated with the incidence of HAPE, and two models were classified according to whether the value of SpO2 (percentage of oxygen in the blood) was available in the target population. Both could accurately predict the risk of HAPE. In the validation cohort, the AUC of model 1 was 0.934 with 95% CI (0.848 to 1.000), and model 2 had an AUC of 0.889, 95% CI (0.779 to 0.999). Calibration plots showed that the predicted and actual HAPE probabilities fitted well with internal validation, and the clinical decision curve shows intervention in the risk range of 0.01–0.98, resulting in a net benefit of nearly 99%.Conclusion The recommended prediction model (nomogram) could estimate the risk of HAPE with good precision, high discrimination and possible clinical applications for patients with HAPE. More importantly, it is an easy-to-execute scoring tool for individuals without medical professionals’ support.

We studied the misalignment between tourism resources and economic development in mountainous cities in the context of limited highway network accessibility. Using Lhasa City as a case study, we illustrated how to evaluate tourism resources and economic development and how to improve tourism resources and promote economic development. The tourism resources possessed by tourism destinations are prerequisites for tourism activities. This study focuses on the coupling coordination relationship between the degree of superiority in tourism resources and the level of economic development in Lhasa City. Data from Lhasa City in 2010, 2015, and 2020 were compared to explore a way of optimizing the spatial pattern of tourism development. The results of this study are as follows. (1) As a typical mountainous area on the Qinghai–Tibet Plateau, the accessibility of Lhasa’s mountainous area largely influences the choice of tourist destinations and is also an important indicator for evaluating the degree of tourism resource superiority. (2) On the whole, the economic development of Lhasa City and the degree of tourism resource superiority is not coordinated, mainly in the low coupling coordination stage, and with the passage of time, the degree of coupling coordination gradually becomes weaker. (3) If a town has advantageous tourism resources with slow economic development, it is easy to fall into the “resource curse” dilemma. In addition, if a town has poor tourism resources, it will be reduced to an outflow area of population and resources after leaving the investment drive, and easy to fall into the dilemma of the “poverty trap”.

To explore the contributions of chemical components in the particulate matter in Lhasa, the size distribution characteristics of the chemical components, such as carbonaceous species (organic carbon, OC; elemental carbon, EC), water-soluble ions (NH4+, Cl−, SO42−, and NO3−) and trace elements (Na, Ca, Al, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, K, Mg, and Pb), were investigated from August 2018 to May 2019. Principal component analysis (PCA) was also used to simulate the source of the particulate matter. The chemical components showed bimodal size distributions, except for Cu. The highest mass concentration of OC appeared at < 0.49 μm, and the second highest one existed at 1.5–3.0 μm in winter or at 3.0–7.2 μm in other seasons. The maximum concentrations of NH4+, Cl−, SO42−, and NO3− were at < 0.49 μm and peaked at 0.95–1.5 μm or > 3.0 μm. For seasonality, the concentrations of NO3− and SO42− were considerably higher in summer and autumn; trace elements (except for Cu, Zn, V, and Ni), OC, and EC presented higher values during late autumn and winter. The ratio between OC and EC (4.15–33.80) indicated the existence of secondary pollution in Lhasa. The [NO3−]–[SO42−] ratios during summer and autumn exceeding 1 suggested that the currently predominant vehicle exhaust made a greater contribution to the aerosols. According to the results of a PCA, the main pollution sources of particulate matter in Lhasa were suspended dust, biomass burning, fossil fuel combustion, secondary pollution, and vehicular emissions.

This study evaluates the abilities of fifteen High-resolution Coupled Model Intercomparison Project phase 6 (CMIP6) models to simulate temperature and precipitation over the Tibetan Plateau (TP) for the years 1980–2014. The impacts of terrain correction and Empirical Orthogonal Function (EOF) correction on simulations of temperature and precipitation are examined. The results show that equal-weighted ensemble averaging of the CMIP6 high-resolution model provides a good representation of the spatial distribution of temperature over the TP, although simulations underestimate observations by 1.87 °C. The simulated spatial range of temperature cooling significantly exceeds the observed range, particularly in the central and southwestern TP. The performances of the simulations for precipitation are far poorer than those for temperature, and although the CMIP6 model represents the distribution of annual mean precipitation, simulations of precipitation show significant deviations from observations. Furthermore, model simulations of precipitation are 1.57 mm lower than observed, and 30% lower than observed in the southeastern TP. However, the CMIP6 model overestimated the intensity of precipitation in most regions, especially in the southeastern part of the TP. Meanwhile, the EOF analysis indicates that the effects of the correction of temperature exceed that of precipitation. Therefore, a range of methods should be considered for correcting temperature and precipitation over a complex terrain.

Berberine (BBR) is used to treat diarrhea clinically. However, its reproductive toxicity is unclear. This study aims to investigate the impact of BBR on the male reproductive system. Intragastric BBR administration for 14 consecutive days results in a significant decrease in the serum testosterone concentration, epididymal sperm concentration, mating rate and fecundity of male mice. Testicular treatment with testosterone propionate (TP) partially reverses the damage caused by BBR to the male reproductive system. Mechanistically, the decrease in Muribaculaceae abundance in the gut microbiota of mice is the principal cause of the BBR-induced decrease in the sperm concentration. Both fecal microbiota transplantation (FMT) and polyethylene glycol (PEG) treatment demonstrate that Muribaculaceae is necessary for spermatogenesis. The intragastric administration of Muribaculaceae intestinale to BBR-treated mice restores the sperm concentration and testosterone levels. Metabolomic analysis reveals that BBR affects arginine and proline metabolism, of which ornithine level is downregulated. Combined analysis via 16S rRNA metagenomics sequencing and metabolomics shows that Muribaculaceae regulates ornithine level. The transcriptomic results of the testes indicate that the expressions of genes related to the low-density lipoprotein receptor (LDLR)-mediated testosterone synthesis pathway decrease after BBR administration. The transcriptional activity of the Ldlr gene in TM3 cells is increased with increased ornithine supplementation in the culture media, leading to increased testosterone synthesis. Overall, this study reveals an association between a BBR-induced decrease in Muribaculaceae abundance and defective spermatogenesis, providing a prospective therapeutic approach for addressing infertility-related decreases in serum testosterone triggered by changes in the gut microbiota composition.

To investigate the vertical distribution of volatile organic compounds (VOCs) concentrations in the Lhasa valley region, an intensive measurement campaign was first conducted in summer using a tethered balloon. The results showed that the average concentration of surface VOCs was 49.1 ± 30.1 ppbv, alkanes and aromatics were the main components. Notably, a very large discrepancy in VOCs was obtained between the wet (71.6 ± 25.9 ppbv) and dry (25.6 ± 8.0 ppbv) episodes, which was attributed to the atmospheric stability and diffusion capacity. Moreover, the total VOC (TVOCs) concentration declined under fluctuations, but it rapidly increased with height in the afternoon during the wet episode (2.50 ppbv/100 m, R 2  = 0.47). According to the PMF results, combustion was the dominant emission source, additionally, the contribution of solvent coating in the wet episode and the background in the dry episode increased with height. Moreover, the O 3 concentration increased with height, and the decrease in L NOx-OH could effectively prevent the occurrence of high O 3 values. This study indicated that low wind speeds and high humidity levels highly likely cause the accumulation of atmospheric VOCs under static and stable conditions, while the control of high O 3 concentrations must still greatly consider summertime NOx emissions in Lhasa., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Our study aimed to compare the prevalence of postoperative fever during the COVID-19 pandemic period with that of the preceding non-pandemic period., Methods: A retrospective analysis was conducted on patients with pectus excavatum (PE) undergoing minimally invasive repair (also called NUSS procedure) at Nanjing Children's Hospital from January 1, 2017 to March 1, 2019 (Group 2019), and from January 1, 2020 to March 1, 2021 (Group 2021). Data from a total of 284 patients, consisting of 200 (70.4%) males and 84 (29.6%) females with an average age of 9.73 ± 3.41 (range, 4 to 17) years, were collected. The presence of post-operative fever (defined as a forehead temperature of 37.5℃ or above within 72 h post-surgery), as well as the time of operation, duration of postoperative mechanical ventilator and urinary catheter use, and length of hospitalization were all assessed in admitted patients from Group 2019 (n = 144) and Group 2021 (n = 140). Postoperative white blood cell (WBC), C-reactive protein (CRP) levels, and prevalence of postoperative complications (i.e., pneumothorax, pulmonary atelectasis, pneumonia, wound infection, and dehiscence) were also determined., Result: Our results showed a statistically significant decrease in the incidence of postoperative fever within 24 to 72 h of surgery in patients admitted from Group 2019 as compared to Group 2021 (p < 0.001), as well as a decrease in peak body temperature within 72 h (p < 0.05). Meanwhile, no significant differences were observed in age and body mass index (BMI), time of operation, or duration of postoperative mechanical ventilator and urinary catheter use between the two groups (p > 0.05). The average hospitalization length of Group 2021 was significantly shorter than Group 2019 (12.49 ± 2.57 vs. 11.85 ± 2.19 days, p < 0.05). Furthermore, while the WBC count between the two groups 24 h after surgery showed a statistical difference (p < 0.05), no differences in CRP levels or the incidence of postoperative complications were observed (p > 0.05)., Conclusion: The prevalence of postoperative fever within 72 h of surgery and the length of hospital stay for patients with PE undergoing NUSS surgery were both decreased in Group 2021. We propose that the above phenomenon may be related to increased used of personal protection equipment (such as surgical masks and filtering facepiece respirators (FFRs)) by physicians, nurses, and the patients themselves., (© 2023. Società Italiana di Pediatria.)

Purpose: Explore the transcription change of brain ischemia and reperfusion injury after deep hypothermic low flow., Method: The data from PRJNA739516 and GSE104036 were obtained for the differentially expressed genes identification, functional enrichment analysis, gene set enrichment analysis, protein-protein interaction construction and hub gene identification. Oxygen and glucose deprivation model was set to validate the hub gene and explore the detailed brain injury mechanism., Result: Interleukin, immunological response, NF-κB signaling pathway, G protein-coupled receptor signaling pathway and NLRP inflammatory are functional pathway were enriched in differentially expressed genes analysis. Sucnr1, Casr, Cxcr4, C5ar1, Tas2r41, Tas2r60 and Hcar2 were identified and verified in the OGD model. Knocking down GPR91 reduces the inflammatory response after OGD and GPR91 may be involved in the inflammatory pre-reaction through the synergistic activation of NF-κB, NLRP3, and IL-1β respectively., Conclusion: Our study found that Interleukin, immunological response, NF-κB signaling pathway, G protein-coupled receptor signaling pathway and NLRP inflammatory are all associated with brain ischemia and reperfusion injury after deep hypothermic low flow and GPR91 can activate NF-κB/NLRP3 pathway and trigger the release of IL-1β in this progress., (© 2023 The Authors.)

Background: Cardiopulmonary bypass may cause malfunction in the myocardium. Cuproptosis is a novel cell death aggregating mitochondrial proteins. However, the research on cardiopulmonary bypass-caused heart tissue injury in immune infiltration and cuproptosis is limited., Method: Immune infiltration, enrichment analysis, protein-protein interaction network, and medication prediction are applied to reanalysis differentially expressed genes and cuproptosis-related genes in gene expression omnibus data set GSE132176., Results: Seven cuproptosis related genes (PDHA1, LIPT1, LIAS, DLST, DLD, DLAT, and DBT) and dendritic cells and Th1 cells are involved in heart tissue injury in response to surgery with cardiopulmonary bypass., Conclusions: Immune infiltration and cuproptosis are potential mechanisms by which cardiopulmonary bypass surgery may cause damage to heart tissue, which may be a new therapeutic target., (© 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Due to the harsh environment in the Tibetan Plateau, traditional grazing greatly limits the growth potential of local animals and causes severe ecosystem degradation. This is an urgent issue to be solved, which requires alternative strategies for grazing animals in the Tibetan alpine pastoral livestock systems. This study aimed to investigate the effects of different feeding strategies on growth performance and ruminal microbiota-host interactions in the local breed of sheep (Gangba sheep). Thirty 9-month old Gangba sheep ( n = 10 per group) were assigned to natural grazing (G), semi-grazing with supplementation (T), and barn feeding (F) groups (supplementation of concentrate and oat hay) based on body weight. At the end of the experiment (75 d), all sheep were weighed, rumen fluid was obtained from six sheep per group, and ruminal epithelium was obtained from 3 sheep per group. The results showed that: (1) Compared with the G and T groups, the F group significantly increased dry matter intake, average daily gain, and feed conversion ratio of animals. Additionally, Gangba sheep in the F group had higher concentrations of ruminal short-chain volatile fatty acids (VFAs), especially propionate and butyrate ( P <0.05) than sheep in the G and T groups. (2) The principal coordinates analysis indicated a significant difference in bacterial composition among different feed strategies. More specifically, the relative abundance of propionate (unidentified F082 and Succiniclasticum ) and butyrate-producing ( Eubacterium&#95;coprostanoligenes&#95;group ) genera were also observed to be increased in the F group, in which unidentified F082 was identified as a differential biomarker among the three groups according to linear discriminant analysis effect size analysis. (3) The dynamics of the rumen epithelial transcriptome revealed that ECM-receptor interactions, focal adhesion, and PI3K-Akt signaling pathways, which are critical in mediating many aspects of cellular functions such as cell proliferation and motility, were upregulated in the F group. In conclusion, under harsh conditions in the Tibetan alpine meadow, barn feeding increased ruminal VFAs concentrations (especially propionate and butyrate), which stimulated gene expression related to cell proliferation in rumen epithelium, appearing to be superior to natural grazing and semi-grazing in gaining body weight of the local Gangba sheep., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jize, Zhuoga, Xiaoqing, Na, Jiacuo, Cuicheng and Bandan.)

Tibetan sheep have lived on the Qinghai-Tibetan Plateau for thousands of years and have good adaptability to the hypoxic environment and strong disease resistance. However, the molecular mechanism by which Tibetan sheep adapt to this extreme environment, especially the role of genetic regulation, is still unknown. Emerging evidence suggests that long noncoding RNAs (lncRNAs) participate in the regulation of a diverse range of biological processes. To explore the potential lncRNAs involved in the adaptation to high-altitude hypoxia of Tibetan sheep, we analysed the expression profile of lncRNAs and mRNAs in the liver and lung tissues of sheep using comparative transcriptome analysis between four Tibetan sheep populations (high altitude) and one Hu sheep population (low altitude). The results showed a total of 7848 differentially expressed (DE) lncRNA transcripts, and 22,971 DE mRNA transcripts were detected by pairwise comparison. The expression patterns of selected mRNAs and lncRNAs were validated by qRT-PCR, and the results correlated well with the transcriptome data. Moreover, the functional annotation analysis based on the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases showed that DE mRNAs and the target genes of the lncRNAs were significantly enriched in organ morphogenesis, response to stimulus, haem binding, the immune system, arginine and proline metabolism, and fatty acid biosynthesis. The prediction of mRNA-mRNA and lncRNA-mRNA interaction networks further revealed transcripts potentially involved in adaptation to high-altitude hypoxia, and the hub genes DDX24, PDCD11, EIF4A3, NDUFA11, SART1, PRPF8 and TCONS&#95;00306477, TCONS&#95;00306029, TCONS&#95;00139593, TCONS&#95;00293272, and TCONS&#95;00313398 were selected. Additionally, a set of target genes, PIK3R1, IGF1R, FZD6, IFNB2, ATF3, MB, CYP2B4, PSMD13, and TGFB1, were also identified as candidate genes associated with high-altitude hypoxia adaptation. In conclusion, a collection of novel expressed lncRNAs, a set of target genes and biological pathways known to be relevant for altitude adaptation were identified by comparative transcriptome analysis between Tibetan sheep and Hu sheep. Our results are the first to identify the characterization and expression profile of lncRNAs between Tibetan sheep and Hu sheep and provide insights into the genetic regulation mechanisms by which Tibetan sheep adapt to high-altitude hypoxic environments., (© 2022. The Author(s).)

Most sheep breeding programs designed for the tropics and sub-tropics have to take into account the impacts of environmental adaptive traits. However, the genetic mechanism regulating the multiple biological processes driving adaptive responses remains unclear. In this study, we applied a selective sweep analysis by combing 1% top values of F st and ZHp on both altitude and geographic subpopulations (APS) in 636 indigenous Tibetan sheep breeds. Results show that 37 genes were identified within overlapped genomic regions regarding F st significantly associated with APS. Out of the 37 genes, we found that 8, 3 and 6 genes at chromosomes (chr.) 13, 23 and 27, respectively, were identified in the genomic regions with 1% top values of ZHp. We further analyzed the INDEL variation of 6 genes at chr.27 (X chromosome) in APS together with corresponding orthologs of 6 genes in Capra, Pantholops, and Bos Taurus. We found that an INDEL was located within 5'UTR region of HAG1 gene. This INDEL of HAG1 was strongly associated with the variation of APS, which was further confirmed by qPCR. Sheep breeds carrying "C-INDEL" of HAG1 have significantly greater body weight, shear amount, corpuscular hemoglobin and globulin levels, but lower body height, than those carrying "CA-INDEL" of HAG1. We concluded that "C-INDEL" variation of HAG1 gene confers better hypoxia tolerance in the highlands of Tibetan and explains well geographic distributions in this population. These results contribute to our understanding of adaptive responses to altitude and geographic adaptation in Tibetan sheep populations and will help to guide future conservation programs for Tibetan sheep native to Qinghai-Tibetan Plateau.

Leptomias sp. belongs to Coleoptera, Curculionidae, Leptomias Faust. It is mainly distributed in the Himalayas and Yarlung Zangbo River valleys in Tibet. It is the first time to report the complete mitochondrial genome of Leptomias sp., which featured a typical circular molecule of 16,801 bp in length, including 13 PCGs, 22 tRNAs, two rRNAs, and one control region. The overall nucleotide composition was 38.7% of A, 10.0% of G, 34.3% of T, and 17.0% of C. The content of A + T was higher than G + C. In this study, we also determined that Leptomias sp. was the sister to the Sympiezomias velatus based the phylogenetic analysis of nucleotide sequence datasets. This study provides a useful resource for further studies on conservation and population genetics of Leptomias species., Competing Interests: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)