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This is an article in the field of mining engineering. The Southern Xizang is one of the main distribution areas of high temperature geothermal zones in China with rich geothermal resources. The chemical analysis and test results of the geothermal water show that the lithium content in the geothermal water of the high temperature geothermal zone in Southern Xizang can reach 34.51 mg/L, and the relative abundance of geothermal lithium is obviously better than that of the world's typical plateau Salt Lake brines, such as Clayton Valley in the Western Plateau of North America and Uyuni in the Andes Plateau of South America. The lithium magnesium ratio is mostly less than 3, which is conducive to lithium extraction from brine. The areas with high lithium content in the geothermal water of the high temperature geothermal zones in Southern Xizang are all distributed in the the Yarlung Zangbo River suture zone and the areas to the south, consistent with the distribution range of lithium rich rocks. At the same time, the Yarlung Zangbo River suture zone and its south area have more Cl-Na geothermal water than the north, and the south has higher TDS and longer circulation path. Based on the stable isotopic composition of hydrogen and oxygen in geothermal water and the provenance of lithium in the surrounding lithium-rich Salt Lake brine, it is inferred that the main sources of lithium in the geothermal water are leaching of lithium-rich rocks by geothermal water and lithium-rich magmatic hydrothermal solutions formed during magmatic differentiation.

Abstract Background Long-term treatment with trimethoprim-sulfamethoxazole (SXT) can lead to the formation of small-colony variants (SCVs) of Staphylococcus aureus. However, the mechanism behind SCVs formation remains poorly understood. In this study, we explored the phenotype and omics-based characterization of S. aureus SCVs induced by SXT and shed light on the potential causes of SCV formation. Methods Stable SCVs were obtained by continuously treating S. aureus isolates using 12/238 µg/ml of SXT, characterized by growth kinetics, antibiotic susceptibility testing, and auxotrophism test. Subsequently, a pair of representative strains (SCV and its parental strain) were selected for genomic, transcriptomic and metabolomic analysis. Results Three stable S. aureus SCVs were successfully screened and proven to be homologous to their corresponding parental strains. Phenotypic tests showed that all SCVs were non-classical mechanisms associated with impaired utilization of menadione, heme and thymine, and exhibited slower growth and higher antibiotic minimum inhibitory concentrations (MICs), compared to their corresponding parental strains. Genomic data revealed 15 missense mutations in 13 genes in the representative SCV, which were involved in adhesion, intramolecular phosphate transfer on ribose, transport pathways, and phage-encoded proteins. The combination analysis of transcriptome and metabolome identified 35 overlapping pathways possible associated with the phenotype switching of S. aureus. These pathways mainly included changes in metabolism, such as purine metabolism, pyruvate metabolism, amino acid metabolism, and ABC transporters, which could play a crucial role in promoting SCVs development by affecting nucleic acid synthesis and energy metabolism in bacteria. Conclusion This study provides profound insights into the causes of S. aureus SCV formation induced by SXT. The findings may offer valuable clues for developing new strategies to combat S. aureus SCV infections.

The combination of photodynamic therapy (PDT)-immunotherapy has brought much hope for cancer patients. However, the hypoxia tumor microenvironment (TME) can regulate tumor angiogenesis and inhibit immune response, thus limiting the therapeutic effects. In this paper, engineered cyanobacteria-M2-like tumor-associated macrophages (TAMs) targeting peptide modified Fe3O4 nanoparticles hybrid system (ECyano@Fe3O4-M2pep) was constructed for alleviating hypoxia and relieving immune suppression to achieve synergistic cancer PDT-immunotherapy. With the irradiation of red laser, oxygen was produced by the photosynthesis of ECyano to alleviate the hypoxia TME. Then, ECyano could secret 5-aminolevulinic acid (5-ALA) under the induction of theophylline for controllable PDT. In the process of PDT, the disulfide bond between ECyano and Fe3O4-M2pep was broken in response to reactive oxygen species (ROS), and then Fe3O4-M2pep was released to target M2-like TAMs, corresponding by the polarization of M2-like TAMs to M1-like TAMs for the killing of tumor cells. Compared with other groups, ECyano@Fe3O4-M2pep + theophylline + laser (ECyano@Fe3O4-M2pep + T + L) group displayed the lowest tumor volume (159.3 mm3) and the highest M1/M2 ratio (1.25- fold). We believe that this hybrid system will offer a promising way for the biomedical application of bacterial therapy.

Fibroblast activation and extracellular matrix (ECM) deposition play an important role in the tracheal abnormal repair process and fibrosis. As a transcription factor, SOX9 is involved in fibroblast activation and ECM deposition. However, the mechanism of how SOX9 regulates fibrosis after tracheal injury remains unclear. We investigated the role of SOX9 in TGF-β1-induced fibroblast activation and ECM deposition in rat tracheal fibroblast (RTF) cells. SOX9 overexpression adenovirus (Ad-SOX9) and siRNA were transfected into RTF cells. We found that SOX9 expression was up-regulated in RTF cells treated with TGF-β1. SOX9 overexpression activated fibroblasts and promoted ECM deposition. Silencing SOX9 inhibited cell proliferation, migration, and ECM deposition, induced G2 arrest, and increased apoptosis in RTF cells. RNA-seq and chromatin immunoprecipitation sequencing (ChIP-seq) assays identified MMP10, a matrix metalloproteinase involved in ECM deposition, as a direct target of SOX9, which promotes ECM degradation by increasing MMP10 expression through the Wnt/β-catenin signaling pathway. Furthermore, in vivo, SOX9 knockdown ameliorated granulation proliferation and tracheal fibrosis, as manifested by reduced tracheal stenosis. In conclusion, our findings indicate that SOX9 can drive fibroblast activation, cell proliferation, and apoptosis resistance in tracheal fibrosis via the Wnt/β-catenin signaling pathway. The SOX9–MMP10–ECM biosynthesis axis plays an important role in tracheal injury and repair. Targeting SOX9 and its downstream target MMP10 may represent a promising therapeutic approach for tracheal fibrosis.

Abstract Despite a more than 100‐year effort to combat malaria, it remains one of the most malignant infectious diseases globally, especially in Africa. Malaria is transmitted by several Anopheles mosquitoes. However, until now few studies have investigated future range dynamics of major An. mosquitoes in Africa through a unified scheme. Through a unified scheme, we developed 21 species distribution models to predict the range dynamics of 21 major An. species in Africa under future scenarios and also examined their overall range dynamic patterns mainly through suitability overlap index and range overlap index. Although future range dynamics varied substantially among the 21 An. species, we predicted large future range expansions for all 21 An. species, and increases in suitability overlap index were detected in more than 90% of the African continent for all future scenarios. Additionally, we predicted high range overlap index in West Africa, East Africa, South Sudan, Angola, and the Democratic Republic of the Congo under future scenarios. Although the relative impacts of land use, topography and climate variables on the range dynamics depended on species and spatial scale, climate played the strongest roles in the range dynamics of most species. Africa might face an increasing risk of malaria transmissions in the future, and better strategies are required to address this problem. Mitigating climate change and human disturbance of natural ecosystems might be essential to reduce the proliferation of An. species and the risk of malaria transmissions in Africa in the future. Our strategies against their impacts should be species‐specific.

Abstract Background With the development of information technology, information has been an important resource in clinical medicine, particularly within the emergency department. Given its role in patient rescue, the emergency department demands a high level of information literacy from nurses to effectively collect, analyze, and apply information due to the urgency and complexity of emergency nursing work. Although prior studies have investigated the information literacy of nursing staff, little has been undertaken in examining the patterns of information literacy and their predictors among emergency department nurses. Aim To clarify the subtypes of information literacy among nurses in the emergency department and explore the factors affecting profile membership. Methods A cross-sectional study was conducted among a convenience sample of 2490 nurses in the emergency department from April to June 2023. The clinical nurses completed the online self-report questionnaires including the general demographic questionnaire, information literacy scale, self-efficacy scale and social support scale. Data analyses involved the latent profile analysis, variance analysis, Chi-square tests and multivariate logistic regression. Results Four latent profiles were identified: ‘Low information literacy (Class 1)’, ‘Moderate information knowledge (Class 2)’, ‘High information knowledge and support (Class 3)’ and ‘High information literacy (Class 4)’, accounting for 20.14%, 42.11%, 23.36% and 14.39%, respectively. Each profile displayed unique characteristics representative of different information literacy patterns. Age, years of work, place of residence, hospital grade, title, professional knowledge, using databases, reading medical literature, participating in information literacy training, self-efficacy, and social support significantly predicted information literacy profile membership. Conclusions Information literacy exhibits different classification features among emergency department nurses, and over half of the nurses surveyed were at the lower or middle level. Identifying sociodemographic and internal-external predictors of profile membership can aid in developing targeted interventions tailored to the needs of emergency department nurses. Nursing managers should actively pay attention to nurses with low information literacy and provide support to improve their information literacy level. Relevance to clinical practice Insights from the current study of the latent profile analysis are beneficial to hospital managers in understanding the different types of emergency department nurses’ information literacy. These insights serve as a reference for managers to enhance nurses’ information literacy levels.

Abstract Background There is a complex relationship between social anxiety and sleep quality. However, network analysis studies of associations between social anxiety and sleep quality are lacking, particularly among patients with breast cancer. The current study aimed to extend this research to a sample of patients with breast cancer and to examine symptom-level associations between social anxiety and sleep quality using network analysis. Methods Network analysis was conducted to explore their associations and identify bridge items of social anxiety and sleep quality. Results The network structure revealed 9 important edges between social anxiety and sleep quality. “Subjective sleep quality” had the highest EI value in the network. “Working difficulty under watching” and “Sleep disorders” had the highest BEI values in their own communities. Conclusion There are complex pathological correlation pathways between social anxiety and sleep quality in breast cancer patients. “Subjective sleep quality”, “Working difficulty under watching” and “Sleep disorders” have the potential to be intervention targets for sleep disorder-social anxiety comorbidity. Medical staff can take corresponding interventions according to the the centrality indices and bridge centrality indicators identified in this study, which is likely to effectively reduce the comorbidity of sleep disorders and social anxiety.

Abstract Background Associations between reproductive factors and breast cancer (BC) risk vary by molecular subtype (i.e., luminal A, luminal B, HER2, and triple negative/basal-like [TNBC]). In this systematic review and meta-analysis, we summarized the associations between reproductive factors and BC subtypes. Methods Studies from 2000 to 2021 were included if BC subtype was examined in relation to one of 11 reproductive risk factors: age at menarche, age at menopause, age at first birth, menopausal status, parity, breastfeeding, oral contraceptive (OC) use, hormone replacement therapy (HRT), pregnancy, years since last birth and abortion. For each reproductive risk factor, BC subtype, and study design (case–control/cohort or case-case), random-effects models were used to estimate pooled relative risks and 95% confidence intervals. Results A total of 75 studies met the inclusion criteria for systematic review. Among the case–control/cohort studies, later age at menarche and breastfeeding were consistently associated with decreased risk of BC across all subtypes, while later age at menopause, later age of first childbirth, and nulliparity/low parity were associated with increased risk of luminal A, luminal B, and HER2 subtypes. In the case-only analysis, compared to luminal A, postmenopausal status increased the risk of HER2 and TNBC. Associations were less consistent across subtypes for OC and HRT use. Conclusion Identifying common risk factors across BC subtypes can enhance the tailoring of prevention strategies, and risk stratification models can benefit from subtype specificity. Adding breastfeeding status to current BC risk prediction models can enhance predictive ability, given the consistency of the associations across subtypes.

Airway fibrosis is among the pathological manifestations of benign central airway obstruction noted in the absence of effective treatments and requires new drug targets to be developed. Slit guidance ligand 2–roundabout guidance receptor 1 (Slit2–Robo1) is involved in fibrosis and organ development. However, its significance in airway fibrosis has not yet been reported. The study explored how the recombinant protein Slit2 functions in transforming growth factor-β1 (TGF-β1)-mediated airway fibrosis in vivo and in vitro. In this study, Slit2 expression initially increased in the tracheal granulation tissues of patients with tracheobronchial stenosis but decreased in the fibrotic tissue. In primary rat tracheal fibroblasts (RTFs), recombinant Slit2 inhibited the expression of extracellular matrices such as Timp1, α-SMA, and COL1A2, whereas recombinant TGF-β1 promoted the expression of Robo1, α-SMA, and COL1A2. Slit2 and TGF-β1 played a mutual inhibitory role in RTFs. Slit2 supplementation and Robo1 downregulation inhibited excessive extracellular matrix (ECM) deposition induced by TGF-β1 in RTFs via the TGF-β1/Smad3 pathway. Ultimately, exogenous Slit2 and Robo1 knockdown-mediated attenuation of airway fibrosis were validated in a trauma-induced rat airway obstruction model. These findings demonstrate that recombinant Slit2 alleviated pathologic tracheobronchial healing by attenuating excessive ECM deposition. Slit2–Robo1 is an attractive target for further exploring the mechanisms and treatment of benign central airway obstruction.

Lung cancer is a chronic wasting disease with insidious onset and long treatment cycle. Exosomes are specialized extracellular vesicles, at first exosomes were considered as a transporter of cellular metabolic wastes, but recently many studies have identified exosomes which contain a variety of biologically active substances that play a role in the regulation of cellular communication and physiological functions. Exosomes play an important role in the development of lung cancer and can promote metastasis through a variety of mechanisms. However, at the same time, researchers have also discovered that immune cells can also inhibit lung cancer through exosomes. In addition, researchers have discovered that some specific miRNAs in exosomes can be used as markers for early diagnosis of lung cancer. Engineering exosomes may be one of the strategies to enhance the clinical translational application of exosomes in the future, for example, strategies such as modifying exosomes to enhance targeting or utilizing exosomes as carriers for drug delivery have been explored. but more studies are needed to verify the safety and efficacy. This article reviews the latest research on exosomes in the field of lung cancer, from the mechanism of lung cancer development, the functions of immune cell-derived exosomes and tumor-derived exosomes, to the early diagnosis of lung cancer.

Background: Lymphocytes are generally accepted to be a key component of the immune response, and an inadequate immune response is closely associated with disease severity and adverse outcomes in hepatitis B virus (HBV)-infected patients. The present study aimed to determine and compare the prognostic values of five lymphocyte-based scores (monocyte-to-lymphocyte ratio [MLR], mean platelet volume-to-lymphocyte ratio [MPVLR], neutrophil-to-lymphocyte ratio [NLR], red cell distribution width-to-lymphocyte ratio [RLR], and C-reactive protein-to-lymphocyte ratio [CLR]) for HBV-associated decompensated cirrhosis (HBV-DC). Methods: Data were extracted from an institutional database. The outcome was 30-day mortality. Receiver operating characteristic curve analyses were conducted, and the resulting area under the curve (AUC) values were used to evaluate the predictive capabilities of the five lymphocyte-based scores for mortality in HBC-DC relative to Model for End-Stage Liver Disease (MELD) score. Results: The study included 273 patients, and the 30-day mortality was 20.9%. Lymphocyte counts were slightly lower in non-survivors than in survivors. The prognostic values of CLR, NLR, MLR, MPVLR, and RLR for mortality in HBV-DC were different. The predictive powers of NLR and MLR were superior to those of the other three scores and similar to that of MELD score. Multivariate analyses identified NLR, MLR, and MELD score as independent prognostic predictors. Conclusion: High NLR and MLR are easily accessible and reliable indicators for predicting 30-day mortality in HBV-DC and have superior prognostic ability compared with other lymphocyte-based scores.

AimThe aim of this study is to investigate the quality of life of nurses who collected nucleic acid samples throughout the COVID-19 epidemic's routine management, as well as the factors that may have influenced it.BackgroundAfter the outbreak of COVID-19, normalized epidemic prevention and control throughout China were implemented. Nucleic acid testing has become an effective measure for the early detection of virus-infected individuals. Nurses collecting nucleic acid samples undertake important tasks. Their quality of life is significant to maintaining team stability and containing the epidemic. However, research on their quality of life is still limited.MethodsA cross-sectional survey was conducted on 1,292 nurses who collected nucleic acid samples from five tertiary general hospitals in Xi'an through self-reported electronic questionnaires (including general demographic information, the Connor–Davidson Resilience Scale, the Social Support Rating Scale, and the World Health Organization Quality of Life Brief Scale). Descriptive, one-way ANOVA and multiple linear regression were performed using SPSS 26.0. Structural equation modeling was used to analyze the influencing factors.ResultsThe nurses collecting nucleic acid samples had a modest level of quality of life. Age, marital status, average daily sleep duration, frequency of exercise, psychological resilience, and social support were all influencing factors of quality of life, according to multiple linear regression analysis. Quality of life was found to be significantly related to psychological resilience and social support.ConclusionDemographic characteristics, psychological resilience, and social support are the factors affecting the quality of life of nurses who collect nucleic acid samples. Nursing managers should focus more on these factors to improve the quality of life for nurses.Relevance to clinical practiceNursing managers should realize the importance of the quality of life of nurses who collect nucleic acid samples in maintaining a vigorous nursing team and ensuring optimized epidemic control. Social support should also be provided to nurses to improve their psychological resilience, thereby improving their quality of life.

As a by-product of the sericulture industry, the utilization rate of silkworm pupa resources is currently not high. Proteins are converted into bioactive peptides through enzymatic hydrolysis. Not only can it solve the utilization problem, but it also creates more valuable nutritional additives. Silkworm pupa protein (SPP) was pretreated with tri-frequency ultrasonic (22/28/40 kHz). Effects of ultrasonic pretreatment on enzymolysis kinetics, enzymolysis thermodynamics, hydrolysate structure as well as hydrolysate antioxidant of SPP were investigated. Ultrasonic pretreatment significantly increased the hydrolysis efficiency, showing a 6.369% decrease in km and a 16.746% increase in kA after ultrasonic action (p < 0.05). The SPP enzymolysis reaction followed a second-order rate kinetics model. Evaluation of enzymolysis thermodynamics revealed that Ultrasonic pretreatment markedly enhanced the SPP enzymolysis, leading to a 21.943% decrease in Ea. Besides, Ultrasonic pretreatment significantly increased SPP hydrolysate’s surface hydrophobicity, thermal stability, crystallinity, and antioxidant activities (DPPH radical scavenging activity, Fe2+ chelation ability, and reducing power). This study indicated that tri-frequency ultrasonic pretreatment could be an efficient approach to enhancing the enzymolysis and improving the functional properties of SPP. Therefore, tri-frequency ultrasound technology can be applied industrially to enhance enzyme reaction process.

Photocatalytic coatings can degrade volatile organic compounds into non-toxic products, which has drawn the attention of scholars around the world. However, the pollution of dust on the coating adversely affects the photocatalytic efficiency and service life of the coating. Here, a series of TiO2-polyfluoroalkoxy (PFA) coatings with different contents of PFA were fabricated by suspension plasma spraying technology. The results demonstrate that the hybrid coatings contain a large number of circular and ellipsoidal nanoparticles and a porous micron-nano structure due to the inclusion of PFA. According to the optimized thermal spraying process parameters, TiO2 nanoparticles were partially melted to retain most of the anatase phases, whereas PFA did not undergo significant carbonization. As compared to the TiO2 coating, the static contact angle of the composite coating doped with 25 wt.% PFA increased from 28.2° to 134.1°. In addition, PFA strongly adsorbs methylene blue, resulting in a greater involvement of methylene blue molecules in the catalyst, where the catalytic rate of hybrid coatings is up to 95%. The presented nanocomposite coatings possess excellent photocatalytic and self-cleaning properties and are expected to find wider practical applications in the field of photocatalysis.

BackgroundInternet gaming disorder (IGD) has become a social problem in children. Evidence from previous studies has proven that anxiety is associated with IGD. However, IGD was always assessed as a whole based on total scores, and the fine-grained relationship between anxiety and IGD was hidden.ObjectiveThe present study aims to investigate the fine-grained relationship between anxiety and IGD in elementary school students during the COVID-19 lockdown, and to identify potential targets for psychological interventions.MethodsDuring the lockdown caused by the COVID-19 pandemic, 667 children from a primary school in China were investigated by the Spence Children’s Anxiety Scale-Short Version and Internet Gaming Disorder Scale. R4.1.1 software was used to construct a network model, assess bridge centrality, and test the robustness of the network and conduct a network.ResultsThere were 23 cross-community edges (weight ranged from −0.03 to 0.12), and each node of anxiety was connected to different nodes of IGD. The nodes with the top 80th percentile bridge expected influence were A2 “social phobia” (0.20), A3 “panic disorder” (0.21) and IGD5 “escape” (0.22). The robustness of the network was acceptable.ConclusionFrom the perspective of network analysis, the present study explored the correlation pathways between anxiety and IGD in children and identified social phobia and panic disorder as the best targets for intervention to reduce IGD.

BackgroundA growing number of research strongly suggest that metabolic syndrome and dyslipidemia contribute to the establishment of a pro-inflammatory state in asthma, according to accumulating data. However, the majority of recent research has focused on the association between lipids and asthma in children and adolescents, with contradictory findings. Consequently, we analyzed the relationship between serum lipid and blood eosinophil counts using data from the NHANES in the USA.MethodsAfter screening the individuals from the 2011 to 2018 NHANES survey, a total of 2,544 out of 39156 participants were eligible for our study. The potential association was discussed using the linear regression model, XGBoost algorithm model, generalized additive model, and two-piecewise linear regression model. In addition, we ran stratified analysis to identify specific demographics.ResultsAfter adjusting for covariates, the result indicated that blood eosinophil counts decreased by 45.68 (-68.56, -22.79)/uL for each additional unit of HDL-C (mmol/L). But serum LDL-C, total cholesterol or triglyceride was not correlated with blood eosinophil counts. Furthermore, we used machine learning of the XGBoost model to determine LDL-C, age, BMI, triglyceride, and HDL-C were the five most critical variables in the blood eosinophil counts. The generalized additive model and two-piecewise linear regression model were used to further identify linear relationship between the serum HDL-C and blood eosinophil counts.ConclusionsOur study elucidated a negative and linear correlation between serum HDL-C and blood eosinophil counts among American asthmatic adults, suggesting that serum HDL-C levels might be associated with the immunological condition of asthmatic adults. There was no correlation between serum LDL-C, total cholesterol, or triglyceride levels and blood eosinophil counts.

Summary: Hypobaric hypoxia (HH) is the primary challenge at highland. Prolonged HH exposure impairs right cardiac function. Mitochondria-associated membrane (MAM) plays a principal role in regulating mitochondrial function under hypoxia, but the mechanism was unclear. In this study, proteomics analysis identified that PACS2, a key protein in MAM, and mitophagy were downregulated in HH. Metabolomics analysis indicated suppression of glucose and fatty acids aerobic oxidation in HH conditions. Cardiomyocyte Pacs2 deficiency disrupted MAM formation and endoplasmic reticulum (ER)-mitochondria calcium flux, further inhibiting mitophagy and energy metabolism in HH. Pacs2 overexpression reversed these effects. Cardiac-specific knockout of Pacs2 exacerbated mitophagy inhibition, cardiomyocyte injury, and right cardiac dysfunction induced by HH. Conditional knock-in of Pacs2 recovered HH-induced right cardiac impairment. Thus, PACS2 is essential for protecting cardiomyocytes through ER-mitochondria calcium flux, mitophagy, and mitochondrial energy metabolism. Our work provides insight into the mechanism of HH-induced cardiomyocyte injury and potential targets for maintaining the right cardiac function at the highland.

Abstract Hypertension is the most common comorbidity in patients with coronavirus disease 2019 (COVID‐19) and increases in‐hospital mortality. Day‐by‐day blood pressure (BP) variability (BPV) is associated with clinical outcomes in hypertensive patients. However, little information is available on the association of BPV with the outcomes of COVID‐19 patients with hypertension. This study aimed to demonstrate whether day‐by‐day in‐hospital BPV had prognostic significance in these patients. The authors included 702 COVID‐19 patients with hypertension from Huoshenshan Hospital (Wuhan, China), who underwent valid in‐hospital BP measurements on at least seven consecutive days. Day‐by‐day BPV was assessed by standard deviation (SD), coefficient of variation (CV), and variation independent of mean (VIM). Overall, patients with severe COVID‐19 and non‐survivors had higher BPV than moderate cases and survivors, respectively. Additionally, higher BPV was correlated with greater age and higher levels of C‐reactive protein, procalcitonin, high‐sensitive cardiac troponin I, and B‐type natriuretic peptide. In multivariable Cox regression, SD of systolic BP (SBP) was predictive of mortality [hazard ratio (HR) 1.17, 95% confidence interval (CI) 1.05–1.30] as well as acute respiratory distress syndrome (ARDS) (HR 1.09, 95% CI 1.01–1.16). Similar trends were observed for CV and VIM of SBP, but not indices of diastolic BP variability. The authors demonstrated that day‐by‐day in‐hospital SBP variability can independently predict mortality and ARDS in COVID‐19 patients with hypertension. And high BPV might be correlated with severe inflammation and myocardial injury. Further studies are needed to clarify whether early reduction of BPV will improve the prognosis of these patients.

Alnus cremastogyne is a rapidly growing broad-leaved tree species that is widely distributed in southwest China. It has a significant economic and ecological value. However, with the expansion of the planting area, the influence of phenotypic variation and differentiation on Alnus cremastogyne has increased, resulting in a continuous decline in its genetic quality. Therefore, it is crucial to investigate the phenotypic variation of Alnus cremastogyne and select excellent breeding materials for genetic improvement. Herein, four growth-related phenotypic traits (diameter at breast height, the height of trees, volume, height under the branches) and twelve reproductive-related phenotypic traits (fresh weight of single cone, dry weight of single cone, seed weight per plant, thousand kernel weight, cone length, cone width, cone length × cone width, fruit shape index, seed rate, germination rate, germination potential, germination index) of 40 clones from four provenances were measured and analyzed. The phenotypic variation was comprehensively evaluated by correlation analysis, principal component analysis and cluster analysis, and excellent clones were selected as breeding materials. The results revealed that there were abundant phenotypic traits variations among and within provenances. Most of the phenotypic traits were highly significant differences (p < 0.01) among provenances. The phenotypic variation among provenances (26.36%) was greater than that of within provenances clones (24.80%). The average phenotypic differentiation coefficient was accounted for 52.61% among provenances, indicating that the phenotypic variation mainly came from among provenances. The coefficient of variation ranged from 9.41% (fruit shape index) to 97.19% (seed weight per plant), and the repeatability ranged from 0.36 (volume) to 0.77 (cone width). Correlation analysis revealed a significantly positive correlation among most phenotypic traits. In principal component analysis, the cumulative contribution rate of the first three principal components was 79.18%, representing the main information on the measured phenotypic traits. The cluster analysis revealed four groups for the 40 clones. Group I and group II exhibited better performance phenotypic traits as compared with group III and group IV. In addition, the four groups are not clearly clustered following the distance from the provenance. Employing the multi-trait comprehensive evaluation method, 12 excellent clones were selected, and the average genetic gain for each phenotypic trait ranged from 4.78% (diameter at breast height) to 32.05% (dry weight of single cone). These selected excellent clones can serve as candidate materials for the improvement and transformation of Alnus cremastogyne seed orchards. In addition, this study can also provide a theoretical foundation for the genetic improvement, breeding, and clone selection of Alnus cremastogyne.

BackgroundApproximately 94% of sensory information acquired by humans originates from the visual and auditory channels. Such information can be temporarily stored and processed in working memory, but this system has limited capacity. Working memory plays an important role in higher cognitive functions and is controlled by central executive function. Therefore, elucidating the influence of the central executive function on information processing in working memory, such as in audiovisual integration, is of great scientific and practical importance.PurposeThis study used a paradigm that combined N-back and Go/NoGo tasks, using simple Arabic numerals as stimuli, to investigate the effects of cognitive load (modulated by varying the magnitude of N) and audiovisual integration on the central executive function of working memory as well as their interaction.MethodsSixty college students aged 17–21 years were enrolled and performed both unimodal and bimodal tasks to evaluate the central executive function of working memory. The order of the three cognitive tasks was pseudorandomized, and a Latin square design was used to account for order effects. Finally, working memory performance, i.e., reaction time and accuracy, was compared between unimodal and bimodal tasks with repeated-measures analysis of variance (ANOVA).ResultsAs cognitive load increased, the presence of auditory stimuli interfered with visual working memory by a moderate to large extent; similarly, as cognitive load increased, the presence of visual stimuli interfered with auditory working memory by a moderate to large effect size.ConclusionOur study supports the theory of competing resources, i.e., that visual and auditory information interfere with each other and that the magnitude of this interference is primarily related to cognitive load.

This study explores the invisible bias quantification of urban governments in their affordable housing service delivery, which can accurately identify the deficiencies of affordable housing policy and alleviate homelessness, poverty, and inequality. We identified complicated eligibility criteria for public rental housing programs in 153 prefectural cities and constructed a public rental housing accessibility index for urban residents and migrants. We used the principal component analysis method; this study offers a new perspective to explore these disparities. We found distinct regional differences in local governments’ behaviors and preferences regarding affordable housing. Cities’ affordable housing provision for migrants is selective and mainly targets young and highly educated migrants. We suggest that local governments pay more attention to elderly migrant workers in affordable housing provision and build a comprehensive evaluation system to set reasonable access conditions to prioritize those with urgent housing needs.

BackgroundSocial avoidance plays an important role in influencing quality of life among patients with breast cancer. Social avoidance behaviors change with treatment periods. However, the trajectory patterns and the predictive factors have not been fully studied.ObjectiveThis study examined the growth trajectory of social avoidance and its predictors in patients with breast cancer.Materials and methodsA total of 176 patients with breast cancer in a university hospital in Shaanxi Province, China, were followed up four times over 6 months following surgery, and data from the final 144 patients were analyzed. The growth mixed model (GMM) was used to identify the trajectory categories, and the predictive factors of the trajectory types were analyzed by logistic regression.ResultsThe best-fit growth mixture modeling revealed three class models: persistent high social avoidance group (Class 1), social avoidance increased first and then decreased group (Class 2), and no social avoidance group (Class 3), accounting for 13.89, 31.94, and 54.17% of patients, respectively. Single-factor analysis showed that family income per capita, residence, and temperament type were related to the social avoidance trajectory. Logistic regression analysis showed that only temperament type was an independent predictor of the social avoidance trajectory, and patients with melancholia were more likely to have persistent high social avoidance.ConclusionOur study proved the heterogeneity of social avoidance behaviors and the influencing effect of temperament type on the development of social avoidance behaviors in Chinese patients with breast cancer. Health professionals should pay more attention to patients who are at higher risk of developing a persistent social avoidance pattern and provide target interventions.

BackgroundFor patients with breast cancer, family functioning is an important factor affecting self-transcendence, which is a key source of happiness. However, network analysis studies of family functioning and self-transcendence are lacking, particularly among patients with breast cancer.PurposeThe present study investigated the network structure of family functioning and self-transcendence in patients with breast cancer and aimed to identify bridge items to provide some theoretical support for the improvement and intervention of self-transcendence in patients with breast cancer.MethodsA total of 294 patients with breast cancer were enrolled in our study. Self-transcendence was evaluated with the Self-Transcendence Scale. Family functioning was evaluated with the Family Adaptation, Participation, Growth, Affection, Resolution (APGAR) Scale. Network analyses were used for the statistical analysis.ResultsIn the network of family functioning and self-transcendence in patients with breast cancer, there were 22 edges across communities, of which the 5 strongest edges connected to the 5 dimensions of family functioning are “Adaptation” with “Enjoyment of hobbies”, “Participation” with “Life enjoyment”, “Growth” with “Acceptance of bodily changes”, “Affection” with “Life enjoyment”, “Resolution” with “Help acceptance”. “Adaptation” had the highest bridge expected influence value (0.30) in the family functioning community, while “Life enjoyment” had the highest bridge expected influence value (0.27) in the self-transcendence community.ConclusionComplex patterns of associations existed in the fine-grained relationship between family functioning and self-transcendence in patients with breast cancer. From the perspective of network analysis, the “Adaptation” aspect of family functioning and the “Life enjoyment” aspect of self-transcendence may be the best targets for improving self-transcendence. These results have important implications to clinical practice, which provided potential targets for interventions to improve self-transcendence from the perspective of family functioning.

AimOur study aimed to investigate the effect of social responsibility on the subjective well-being of volunteers for COVID-19 and to examine the mediating role of job involvement in this relationship.BackgroundNowadays, more and more people join volunteer service activities. As we all know, volunteer work contributes to society without any return. Volunteers often have a strong sense of social responsibility and reap subjective well-being in their dedication. Although research shows that social responsibility will drive them to participate in volunteer work actively, it is less clear whether job involvement will impact their subjective well-being.MethodsThe data were collected in the precaution zone in Shanghai, China, from April to May 2022. A sample of 302 volunteers for COVID-19 completed the social responsibility scale, subjective well-being scale and job involvement scale in the form of an electronic questionnaire on their mobile phones. A structural equation model was adopted to verify the research hypotheses.ResultsSocial responsibility was significantly and positively related to volunteers’ subjective well-being and job involvement (p

Based on the spillover index and an improved spillover asymmetric measure method, this paper studies the volatility spillover and its asymmetric effect between crude oil and agricultural commodity futures in pre- and post-outbreak of COVID-19. We find that the total volatility spillover is higher with pre-outbreak of COVID-19. In addition, the volatility spillover caused by China’s crude oil is more prominent than international crude oil around the COVID-19, which highlights the necessity of risk control through the establishment of an energy financial market in China. Finally, although the asymmetric effect of volatility spillover has always existed, crude oil was less impacted by good news post-outbreak of COVID-19, indicating that the outbreak of COVID-19 makes assets dominated by commodity attributes more sensitive to bad news. These findings are beneficial for investors to establish a cross-sector risk hedging portfolio, and provide empirical evidence for policymakers to ensure energy and food security.

A newly-developed platform, the Illumina TruSeq Methyl Capture EPIC library prep (TruSeq EPIC), builds on the content of the Infinium MethylationEPIC Beadchip Microarray (EPIC-array) and leverages the power of next-generation sequencing for targeted bisulphite sequencing. We empirically examined the performance of TruSeq EPIC and EPIC-array in assessing genome-wide DNA methylation in breast tissue samples. TruSeq EPIC provided data with a much higher density in the regions when compared to EPIC-array (~2.74 million CpGs with at least 10X coverage vs ~752 K CpGs, respectively). Approximately 398 K CpGs were common and measured across the two platforms in every sample. Overall, there was high concordance in methylation levels between the two platforms (Pearson correlation r = 0.98, P

Abstract Acute high‐altitude (HA) exposure induces physiological responses of the heart and blood pressure (BP). However, few studies have investigated the responses associated with dipper and non‐dipper BP patterns. In this prospective study, 72 patients underwent echocardiography and 24‐h ambulatory BP testing at sea level and HA. Patients were divided into dipper and non‐dipper groups according to BP at sea level. Acute HA exposure elevated 24‐h systolic and diastolic BP and increased BP variability, particularly in the morning. Moreover, acute exposure increased left ventricular torsion, end‐systolic elastance, effective arterial elastance, and untwisting rate, but reduced peak early diastolic velocity/late diastolic velocity and peak early diastolic velocity/early diastolic velocity, implying enhanced left ventricular systolic function but impaired filling. Dippers showed pronounced increases in night‐time BP, while non‐dippers showed significant elevation in day‐time BP, which blunted differences in nocturnal BP fall, and lowest night‐time and evening BP. Dippers had higher global longitudinal strain, torsion, and untwisting rates after acute HA exposure. Variations in night‐time systolic BP correlated with variations in torsion and global longitudinal strain. Our study firstly demonstrates BP and cardiac function variations during acute HA exposure in different BP patterns and BP increases in dippers at night, while non‐dippers showed day‐time increases. Furthermore, enhanced left ventricular torsion and global longitudinal strain are associated with BP changes. Non‐dippers showed poor cardiac compensatory and maladaptive to acute HA exposure. However, the exact mechanisms involved need further illumination.

Aim: Psoriasis vulgaris (PV) is a complicated autoimmune disease characterized by erythema of the skin and a lack of available cures. PV is associated with an increased risk of metabolic syndrome and cardiovascular disease, which are both mediated by the interaction between systemic inflammation and aberrant metabolism. However, whether there are differences in the lipid metabolism between different levels of severity of PV remains elusive. Hence, we explored the molecular evidence for the subtyping of PV according to alterations in lipid metabolism using serum metabolomics, with the idea that such subtyping may contribute to the development of personalized treatment.Methods: Patients with PV were recruited at a dermatology clinic and classified based on the presence of metabolic comorbidities and their Psoriasis Area and Severity Index (PASI) from January 2019 to November 2019. Age- and sex-matched healthy controls were recruited from the preventive health department of the same institution for comparison. We performed targeted metabolomic analyses of serum samples and determined the correlation between metabolite composition and PASI scores.Results: A total of 123 participants, 88 patients with PV and 35 healthy subjects, were enrolled in this study. The patients with PV were assigned to a “PVM group” (PV with metabolic comorbidities) or a “PV group” (PV without metabolic comorbidities) and further subdivided into a “mild PV” (MP, PASI

ObjectiveThe psychological problems of frontline nurses in COVID-19 prevention and control are very prominent, and targeted intervention is needed to alleviate them. This study was to assess the impact of online intervention programs on psychological crisis of anxiety, depression levels and physical symptoms among frontline nurses fighting the COVID-19 pandemic.MethodsA three-stage online psychological crisis intervention program was established. The General Anxiety 7 (GAD-7) assessment, Patient Health Questionnaire-9 (PHQ-9), and the Self-rating Somatic Symptom Scale (SSS) were used to evaluate the effect of intervention on the day before entering isolation wards (Time 1), the first day after leaving the isolation ward (Time 2), and at the end of the intervention (Time 3).ResultsSixty-two nurses completed the study, including 59 female (95.2%) and three male nurses (4.8%) with an age range of 23–49 (mean 33.37 ± 6.01). A significant (P < 0.01) difference existed in the scores of GAD-7, PHQ-9, and SSS at different intervention periods. The GAD-7 score was significantly (P < 0.001) lower at the end of quarantine period (time 3) than that before entering the isolation wards (time 1) or after leaving the isolation wards (time 2), the PHQ-9 score was significantly (P = 0.016) lower at the end of quarantine period (time 3) than that after leaving the isolation wards (time 2), and the SSS score was significantly (P < 0.001) lower at the end of quarantine period (time 3) than that before entering the isolation wards (time 1) or after leaving the isolation wards (time 2).ConclusionThe three-stage online intervention program based on the psychological crisis can be effective in reducing negative emotions and somatic symptoms and improving the mental health of frontline nurses in prevention and control of the COVID-19 epidemic. It may provide an empirical basis for psychological crisis intervention of frontline medical staff when facing public health emergencies.

Climate change impacts agricultural production negatively. Therefore, rural residents experience large income and consumption fluctuations when dealing with climate change risks. However, little is known about whether digital financial inclusion can help rural residents improve their ability to resist climate change. This study uses the Peking University Digital Financial Inclusion Index of China and China Household Finance Survey data, together with historical temperature data from major cities, to study the impact of digital financial inclusion on Chinese rural residents’ consumption in response to climate change. The results suggest that digital financial inclusion significantly promotes rural households’ total consumption and consumption upgrades. Heterogeneity analyses also show that digital financial inclusion predominantly affects low-income households, low-asset households, and households living in China’s central and western regions. The instrumental variable and control function methods were used for robustness, and our main conclusions are robust and reliable. Although climate change reduces rural residents’ consumption and increases their risks, digital finance inclusion significantly mitigates this negative effect. The government can increase the usage depth of digital financial inclusion in rural areas by promoting the construction of digital financial inclusion facilities. The government should strive to deepen the impact of digital financial inclusion on rural household income and consumption to further improve their ability to resist climate risks.

Abstract Background Cellulosimicrobium cellulans is a gram-positive filamentous bacterium found primarily in soil and sewage that rarely causes human infection, especially in previously healthy adults, but when it does, it often indicates a poor prognosis. Case presentation We report a case of endocarditis and intracranial infection caused by C. cellulans in a 52-year-old woman with normal immune function and no implants in vivo. The patient started with a febrile headache that progressed to impaired consciousness after 20 days, and she finally died after treatment with vancomycin combined with rifampicin. C. cellulans was isolated from her blood cultures for 3 consecutive days after her admission; however, there was only evidence of C. cellulans sequences for two samples in the second-generation sequencing data generated from her peripheral blood, which were ignored by the technicians. No C. cellulans bands were detected in her cerebrospinal fluid by second-generation sequencing. Conclusions Second-generation sequencing seems to have limitations for certain specific strains of bacteria.

Abstract Background The data on the prevalence of resistance to mupirocin (MUP), fusidic acid (FA) and retapamulin (RET) in methicillin-resistant Staphylococcus aureus (MRSA) from China are still limited. This study aimed to examine these three antibiotics resistance in 1206 MRSA clinical isolates from Eastern China. Phenotypic MUP, FA and RET resistance was determined by minimum inhibitory concentrations (MICs), and genotypic by PCR and DNA sequencing of the mupA/B, fusB-D, cfr, vgaA/Av/A LC /B/C/E, lsaA-C/E and salA and mutations in ileS, fusA/E, rplC, and 23S RNA V domain. The genetic characteristics of resistance isolates were conducted by pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Results Overall MRSA MUP, FA and RET resistance was low (5.1, 1.0 and 0.3%, respectively). MupA was the mechanism of high-level MUP resistance. All low-level MUP resistance isolates possessed an equivocal mutation N213D in IleS; of these, 2 reported an additional V588F mutation with an impact on the Rossman fold. FusA mutations, such as L461K, H457Q, H457Y and V90I were the primary FA mechanisms among high-level resistance isolates, most of which also contained fusC; however, all low-level resistance strains carried fusB. Except lsaE gene detected in one isolate, no other resistance mechanisms tested were found among RET-resistant isolates. Additionally, sixteen PFGE types (A-P) were observed, among which type B was the most common (49/76, 64.5%), followed by types E and G (4/76, 5.3% each) and types C and M (3/76, 3.9% each). All resistant strains were divided into 15 ST types by MLST. ST764 (24/76, 31.6%), ST630 (11/76, 14.5%), ST239 (9/76, 11.8%) and ST5 (7/76, 9.2%) were the major types. PFGE type B isolates with the aforementioned STs were mainly found in mupirocin resistant isolates. Conclusions MUP, FA and RET exhibited highly activity against the MRSA isolates. Acquired genes and chromosome-borne genes mutations were responsible for MUP and FA resistance; however, the mechanism for some RET-resistant isolates remains to be further elucidated. Also, the surveillance to MUP in MRSA should be strengthened to prevent elevated resistance due to the expansion of clones.

AimOur previous proteomic analysis showed that small RNA SprC (one of the small pathogenicity island RNAs) of Staphylococcus aureus possesses the ability to regulate the expression of multiple bacterial proteins. In this study, our objective was to further provide insights into the regulatory role of SprC in gene transcription and metabolism of S. aureus.MethodsGene expression profiles were obtained from S. aureus N315 wild-type and its sprC deletion mutant strains by RNA-sequencing (RNA-seq), and differentially expressed genes (DEGs) were screened by R language with a |log2(fold change)| ≥1 and a false discovery rate (FDR) ≤ 0.05. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were carried out to understand the significance of the DEGs. The quality of RNA-seq was further verified by quantitative real-time PCR (qRT-PCR), mRNA target prediction, metabolomics analysis and transcript-level expression analysis of genes of sprC complementation strain.ResultsA total of 2497 transcripts were identified, of which 60 transcripts expressions in sprC knockout strain were significantly different (37 up-regulated and 23 down-regulated DEGs). GO analysis showed that the functions of these DEGs were mainly concentrated in the biological process and molecular function related to metabolism and pathogenesis, and a higher number of genes were involved in the oxidation-reduction process, catalytic activity and binding. KEGG pathways enrichment analysis demonstrated that metabolism and pathogenesis were the most affected pathways, such as metabolic pathways, biosynthesis of secondary metabolites, purine metabolism, fructose and mannose metabolism and S. aureus infection. The qRT-PCR results of the DEGs with defined functions in the sprC deletion and complementation strains were in general agreement with those obtained by RNA-seq. Metabolomics analysis revealed 77 specific pathways involving metabolic pathways. Among them, many, such as metabolic pathways, biosynthesis of secondary metabolites and purine metabolism, were consistent with those enriched in the RNA-seq analysis.ConclusionThis study offered valuable and reliable information about the regulatory roles of SprC in S. aureus biology through transcriptomics and metabolomics analysis. These results may provide clues for new potential targets for anti-virulence adjuvant therapy on S. aureus infection.

Inflammatory myofibroblastic tumor (IMT) is a mesenchymal spindle cell tumour with low malignant potential which is extremely rare in breasts. Because of the lack of typical imaging and clinical characteristics of IMT, it is easy to misdiagnose before operation. We now report a case of a 37-year-old woman presenting with a mass in her left breast. Ultrasound showed a well-circumscribed lesion in the lower outer quadrant. The patient underwent lumpectomy, and histopathology revealed a tumor which was composed of fusiform cells and inflammatory cells. Immunohistochemistry (IHC) showed tumor cells are positive for vimentin, ALK, BCL2, and SMA. The FISH test demonstrated ALK (2p23) chromosomal translocation (ALK positive). The final diagnosis of breast IMT was rendered with nonclassical morphology. Postoperative 30-month follow-up no evidence showed residual tumor or recurrence. As a very rare tumor, breast IMT could be easily misdiagnosed clinically and pathologically. Complete surgical resection of the tumor is preferred, and it has the risk of recurrence and metastasis.

Background: Acute high altitude (HA) exposure results in blood pressure (BP) variations in most subjects. Previous studies have demonstrated that higher BP is potentially correlated with acute mountain sickness (AMS). The BP load may be of clinical significance regarding systemic circulation status.Objectives: This study aimed to examine HA-induced BP changes in patients with AMS compared to those in healthy subjects. Further, we provided clinical information about the relationship between variations in 24-h ambulatory parameters (BP level, BP variability, and BP load) and AMS.Methods: Sixty-nine subjects were enrolled and all participants ascended Litang (4,100 m above sea level). They were monitored using a 24-h ambulatory blood pressure device and underwent echocardiography within 24 h of altitude exposure. The 2018 Lake Louise questionnaire was used to evaluate AMS.Results: The AMS group comprised more women than men [15 (65.2%) vs. 13 (28.3%), P < 0.001] and fewer smokers [4 (17.4%) vs. 23 (50.0%), P = 0.009]. The AMS group exhibited significant increases in 24-h BP compared to the non-AMS group (24-h SBP variation: 10.52 ± 6.48 vs. 6.03 ± 9.27 mmHg, P = 0.041; 24-h DBP variation: 8.70 ± 4.57 vs. 5.03 ± 4.98 mmHg, P = 0.004). The variation of mean 24-h cBPL (cumulative BP load) (mean 24-h cSBPL: 10.58 ± 10.99 vs. 4.02 ± 10.58, P = 0.016; 24-h mean cDBPL: 6.03 ± 5.87 vs. 2.89 ± 4.99, P = 0.034) was also obviously higher in AMS subjects than in non-AMS subjects after HA exposure. 24-h mean cSBPL variation (OR = 1.07, P = 0.024) and 24-h mean cDBPL variation (OR = 1.14, P = 0.034) were independent risk factors of AMS. Moreover, variation of 24-h mean cSBPL showed a good correlation with AMS score (R = 0.504, P < 0.001).Conclusions: Our study demonstrated that patients with AMS had higher BP and BP load changes after altitude exposure than healthy subjects. Excessive BP load variations were associated with AMS. Thus, BP load could be an effective indicator regarding systemic circulation status of AMS.

Abstract Aluminum toxicity is considered the main factor underlying nutrient deficiencies and growth limitations of plants in acidic soil. Red clover (Trifolium pratense L.) is an important legume grass distributed worldwide, and it has medicinal value and strong adaptability to acidic soil with Al. However, few studies have focused on the relationship between nutrient uptake and Al stress. In this study, the changes in nutrients in the organs (root, stem, and leaf) of the cultivars Brilliant, Dory, and Haifa under high aluminum stress were detected. The results indicated that the contents of macronutrients and micronutrients were significantly influenced by Al3+ concentrations and the interaction between Al3+ concentrations and cultivars (P

We aimed to develop an artificial intelligence (AI) diagnosis system for uterine smooth muscle tumors (UMTs) by using deep learning. We analyzed the morphological features of UMTs on whole-slide images (233, 108, and 30 digital slides of leiomyosarcomas, leiomyomas, and smooth muscle tumors of uncertain malignant potential stained with hematoxylin and eosin, respectively). Aperio ImageScope software randomly selected ≥10 areas of the total field of view. Pathologists randomly selected a marked region in each section that was no smaller than the total area of 10 high-power fields in which necrotic, vascular, collagenous, and mitotic areas were labeled. We constructed an automatic identification algorithm for cytological atypia and necrosis by using ResNet and constructed an automatic detection algorithm for mitosis by using YOLOv5. A logical evaluation algorithm was then designed to obtain an automatic UMT diagnostic aid that can “study and synthesize” a pathologist’s experience. The precision, recall, and F1 index reached more than 0.920. The detection network could accurately detect the mitoses (0.913 precision, 0.893 recall). For the prediction ability, the AI system had a precision of 0.90. An AI-assisted system for diagnosing UMTs in routine practice scenarios is feasible and can improve the accuracy and efficiency of diagnosis.

Allelic variation in floral quantitative traits, including the elements of flowers and fruits, is caused by extremely complex regulatory processes. In the genetic improvement of flare tree peony (Paeonia rockii), a unique ornamental and edible oil woody species in the genus Paeonia, a better understanding of the genetic composition of these complex traits related to flowers and fruits is needed. Therefore, we investigated the genetic diversity and population structure of 160 P. rockii accessions and conducted single-marker association analysis for 19 quantitative flower and fruit traits using 81 EST-SSR markers. The results showed that the population had a high phenotypic diversity (coefficients of variation, 11.87–110.64%) and a high level of genetic diversity (mean number of alleles, NA = 6.09). These accessions were divided into three subgroups by STRUCTURE analysis and a neighbor-joining tree. Furthermore, we also found a low level of linkage disequilibrium between these EST-SSRs and, by single-marker association analysis, identified 134 significant associations, including four flower traits with 11 EST-SSRs and 10 fruit traits with 32 EST-SSRs. Finally, based on the sequence alignment of the associated markers, P280, PS2, PS12, PS27, PS118, PS131, and PS145 may be considered potential loci to increase the yield of flare tree peony. These results laid the foundation for further analysis of the genetic structure of some key traits in P. rockii and had an obvious potential application value in marker-assisted selection breeding.

Background: Acute high-altitude (HA) exposure results in blood pressure (BP) and cardiac function variations in most subjects, some of whom suffer from acute mountain sickness (AMS). Several previous studies have found that cardiovascular function indicators are potentially correlated with AMS.Objectives: This study aims to examine HA-induced cardiovascular adaptations in AMS patients and compare them with healthy subjects. It also aims to investigate the relationship between cardiovascular function indicators and AMS, as well as to provide some insightful information about the prevention and treatment of AMS.Methods: Seventy-two subjects were enrolled in this cohort study. All the subjects ascended Litang (4,100 m above sea level). They were monitored by a 24-h ambulatory blood pressure (ABP) device and underwent echocardiography examination within 24 h of altitude exposure. The 2018 Lake Louise questionnaire was used to evaluate AMS.Results: Acute mountain sickness group consisted of more women (17 [60.7%] vs. 10 [22.7%], p = 0.001) and fewer smokers (5 [17.9%] vs. 23 [52.3%], p = 0.003). Compared with subjects without AMS, subjects with AMS had lower pulse pressure (PP) (daytime PP, 45.23 ± 7.88 vs. 52.14 ± 4.75, p < 0.001; nighttime PP, 42.81 ± 5.92 vs. 49.39 ± 7.67, p < 0.001) and lower effective arterial elastance (Ea) (1.53 ± 0.24 vs. 1.73 ± 0.39, p = 0.023). Multivariate regression indicated that female sex (OR = 0.23, p = 0.024), lower daytime PP (OR = 0.86, p = 0.004), and lower Ea (OR = 0.03, p = 0.015) at low altitude (LA) were independent risk factors for AMS. Combined daytime PP and Ea at LA had a high predictive value for AMS (AUC = 0.873; 95% CI: 0.789–0.956). Correlation analysis showed that AMS-induced headache correlated with daytime PP (R = −0.401, p < 0.001) and nighttime PP at LA (R = −0.401, p < 0.001).Conclusion: Our study demonstrated that AMS patients had a lower PP and Ea at LA. These baseline indicators of vasodilation at LA were closely associated with AMS, which may explain the higher headache severity in subjects with higher PP at LA.

With the rapid depletion of mineral resources, deep prospecting is becoming a frontier field in international geological exploration. The prediction of deep mineral resources is the premise and foundation of deep prospecting. However, conventional metallogenic predictive methods, which are mainly based on surface geophysical, geochemical, and remote sensing data and geological information, are no longer suitable for deep metallogenic prediction due to the large burial depth of deep-seated deposits. Consequently, 3D metallogenic prediction becomes a critical method for delineating deep prospecting target areas. As a world-class giant gold metallogenic province, the Jiaodong Peninsula is at the forefront in China in terms of deep prospecting achievements and exploration depth. Therefore, it has unique conditions for 3D metallogenic prediction and plays an important exemplary role in promoting the development of global deep prospecting. This study briefly introduced the method, bases, and results of the 3D metallogenic prediction in the northwest Jiaodong Peninsula and then established 3D geological models of gold concentration areas in the northwest Jiaodong Peninsula using drilling combined with geophysics. Since gold deposits in the northwest Jiaodong Peninsula are often controlled by faulting in the 3D space, this study proposed a method for predicting deep prospecting target areas based on a stepped metallogenic model and a method for predicting the deep resource potential of gold deposits based on the shallow resources of ore-controlling faults. Multiple characteristic variables were extracted from the 3D geological models of the gold concentration areas, including the buffer zone and dip angle of faults, the changing rate of fault dip angle, and the equidistant distribution of orebodies. Using these characteristic variables, five deep prospecting target areas in the Jiaojia and Sanshandao faults were predicted. Moreover, based on the proven gold resources at an elevation of −2000 m and above, the total gold resources of the Sanshandao, Jiaojia, and Zhaoping ore-controlling faults at an elevation of −5000–−2000 m were predicted to be approximately 3377–6490 t of Au. Therefore, it is believed that the total gold resources in the Jiaodong Peninsula are expected to exceed 10,000 t. These new predicted results suggest that the northwest Jiaodong Peninsula has huge potential for the resources of deep gold deposits, laying the foundation for further deep prospecting.

IntroductionPulmonary artery pressure (PAP) is increased and right ventricular (RV) function is well preserved in healthy subjects upon exposure to high altitude (HA). An increase in PAP may trigger notching of the right ventricular outflow tract Doppler flow velocity envelope (RVOT notch), which is associated with impaired RV function in patients with pulmonary hypertension. However, whether HA exposure can induce RVOT notch formation and the subsequent impact on cardiac function in healthy subjects remains unclear.MethodsA total of 99 subjects (69 males and 30 females) with a median age of 25 years were enrolled in this study; they traveled from 500 to 4100 m by bus over a 2-day period. All subjects underwent a comprehensive physiological and echocardiographic examination 1 day before ascension at low altitude and 15 ± 3 h after arrival at HA. The RVOT notch was determined by the presence of a notched shape in the RVOT Doppler flow velocity envelope. The systolic PAP (SPAP) was calculated as Bernoulli equation SPAP = 4 × (maximum tricuspid regurgitation velocity)2+5 and mean PAP (mPAP) = 0.61 × SPAP+2. Cardiac output was calculated as stroke volume × heart rate. Pulmonary capillary wedge pressure (PCWP) was calculated as 1.9+1.24 × mitral E/e’. Pulmonary vascular resistance (PVR) was calculated as (mPAP-PCWP)/CO.ResultsAfter HA exposure, 20 (20.2%) subjects had an RVOT notch [notch (+)], and 79 (79.8%) subjects did not have an RVOT notch [notch (−)]. In the multivariate logistic regression analysis, the SPAP, right ventricular global longitude strain (RV GLS), and tricuspid E/A were independently associated with the RVOT notch. The SPAP, mPAP, PVR, standard deviations of the times to peak systolic strain in the four mid-basal RV segments (RVSD4), peak velocity of the isovolumic contraction period (ICV), and the peak systolic velocity (s’) at the mitral/tricuspid annulus were increased in all subjects. Conversely, the pulse oxygen saturation (SpO2), RV GLS, and tricuspid annulus plane systolic excursion (TAPSE)/SPAP were decreased. However, the increases of SPAP, mPAP, PVR, and RVSD4 and the decreases of SpO2, RV GLS, and TAPSE/SPAP were more pronounced in the notch (+) group than in the notch (−) group. Additionally, increased tricuspid ICV and mitral/tricuspid s’ were found only in the notch (−) group.ConclusionHA exposure-induced RVOT notch formation is associated with impaired RV function, including no increase in the tricuspid ICV or s’, reduction of RV deformation, deterioration in RV-pulmonary artery coupling, and RV intraventricular synchrony.

BackgroundAcute high altitude (HA) exposure elicits blood pressure (BP) responses in most subjects, and some of them suffer from acute mountain sickness (AMS). However, a 24-h ambulatory BP (ABP) change and the correlation with the occurrence of AMS in different sexes are still unclear.ObjectivesThis prospective study aimed to investigate HA induced BP responses in males and females and the relationship between AMS and 24-h ABP.MethodsForty-six subjects were matched according to demographic parameters by propensity score matching with a ratio of 1:1. All the subjects were monitored by a 24-h ABP device; the measurement was one period of 24 h BP. 2018 Lake Louise questionnaire was used to evaluate AMS.ResultsBoth the incidence of AMS (14 [60.9%] vs. 5 [21.7%], P = 0.007) and headache (18 [78.3%] vs. 8 [34.8%], P = 0.003) were higher in females than in males. All subjects showed an elevated BP in the early morning [morning systolic BP (SBP), 114.72 ± 13.57 vs. 120.67 ± 11.10, P = 0.013]. The elevation of morning SBP variation was more significant in females than in males (11.95 ± 13.19 vs. −0.05 ± 14.49, P = 0.005), and a higher morning BP surge increase (4.69 ± 18.09 vs. −9.66 ± 16.96, P = 0.005) was observed after acute HA exposure in the female group. The increase of morning SBP was associated with AMS occurrence (R = 0.662, P < 0.001) and AMS score (R = 0.664, P = 0.001). Among the AMS symptoms, we further revealed that the incidence (R = 0.786, P < 0.001) and the severity of headache (R = 0.864, P < 0.001) are closely correlated to morning SBP.ConclusionsOur study demonstrates that females are more likely to suffer from AMS than males. AMS is closely associated with elevated BP in the early morning period, which may be correlated to higher headache incidence in subjects with higher morning SBP.

Male novel coronavirus disease (COVID-19) patients tend to have poorer clinical outcomes than female patients, while the myocardial injury is strongly associated with COVID-19-related adverse events. Owing to a lack of corresponding data, we aimed to investigate the sex differences in the incidence of myocardial injury in COVID-19 patients and to identify the potential underlying mechanisms, which may partly account for the sex bias in the incidence of adverse events. This retrospective study included 1,157 COVID-19 patients who were hospitalized in Huoshenshan Hospital from 12 March 2020 to 11 April 2020. Data on the patients’ demographic characteristics, initial symptoms, comorbidities and laboratory tests were collected. Totally, 571 (49.4%) female and 586 (50.6%) male COVID-19 patients were enrolled. The incidence of myocardial injury was higher among men than women (9.2 vs. 4.9%, p = 0.004). In the logistic regression analysis, age, and chronic kidney disease were associated with myocardial injury in both sexes. However, hypertension [odds ratio (OR) = 2.25, 95% confidence interval (CI) 1.20–4.22], coronary artery disease (OR = 2.46, 95% CI 1.14–5.34), leucocyte counts (OR = 3.13, 95% CI 1.24–7.86), hs-CRP (OR = 4.45, 95% CI 1.33–14.83), and D-dimer [OR = 3.93 (1.27–12.19), 95% CI 1.27–12.19] were independent risk factors only in the men. The correlations of hs-CRP and D-dimer with hs-cTnI and BNP were stronger in the men. The incidence of myocardial injury in COVID-19 patients is sex-dependent, predominantly in association with a greater degree of inflammation and coagulation disorders in men. Our findings can be used to improve the quality of clinical management in such settings.

BackgroundHigh altitude exposure induces overload of right-sided heart and may further predispose to supraventricular arrhythmia. It has been reported that atrial mechanical dyssynchrony is associated with atrial arrhythmia. Whether high altitude exposure causes higher right atrial (RA) dyssynchrony is still unknown. The aim of study was to investigate the effect of high altitude exposure on right atrial mechanical synchrony.MethodsIn this study, 98 healthy young men underwent clinical examination and echocardiography at sea level (400 m) and high altitude (4100 m) after an ascent within 7 days. RA dyssynchrony was defined as inhomogeneous timing to peak strain and strain rate using 2D speckle-tracking echocardiography.ResultsFollowing high altitude exposure, standard deviation of the time to peak strain (SD-TPS) [36.2 (24.5, 48.6) ms vs. 21.7 (12.9, 32.1) ms, pConclusionOur data for the first time demonstrated that high altitude exposure causes RA dyssynchrony in healthy young men, which may be secondary to increased pulmonary arterial pressure. In addition, subjects with higher RA dyssynchrony presented worse RA contractile function and right ventricular performance.

Antibiotics have been described to modulate bacterial virulence gene expression. This study aimed to assess the changes caused by anti-Staphylococcus agents in the transcription of leucocidin ED (lukED) gene of Staphylococcus aureus strain Newman in vitro and in vivo and to determine whether the altered expression is agr dependent. The bacteria were exposed to subinhibitory concentrations [1/2, 1/4, or 1/8 minimal inhibitory concentration (MIC)] of 11 antibiotics, and the expression of lukE and agr-effector RNAIII was determined using qRT-PCR. In vivo experiments were performed to evaluate the impact exerted by six representative antibiotics on the transcription of both genes. Molecular analysis showed that in vitro lukE transcription was dramatically promoted in the Newman strain exposed to sub-MICs of vancomycin, trimethoprim–sulfamethoxazole, clindamycin, gentamicin, daptomycin, and ciprofloxacin and considerably reduced when stimulated by cefazolin, erythromycin, rifampicin, tigecycline, and linezolid. In the murine abscess model, tigecycline significantly decreased the transcription of lukE and the bacterial numbers, whereas vancomycin increased them; although cefazolin increased the lukE expression (contrary to the in vitro effect), it had a remarkable role in reducing bacterial load. The correspondence analysis shows that RNAIII expression varied under seven of 11 antibiotics in vitro, and six drugs in vivo were consistent with lukE transcripts. In conclusion, our data show that anti-Staphylococcus antibiotics exert modulatory effects on lukE expression in vitro and/or in vivo, and the changed expression caused by some drugs may be involved with agr activity, thus providing a guide to choose appropriate agents to avoid promoting bacterial virulence in lukED-positive S. aureus infections.

The immune checkpoint blockade (ICB) immunotherapy has prolonged overall survival for cancer patients but the response rates are low. The resistance to ICB is likely due to compensatory upregulation of additional immune inhibitory molecules. In this study, we first systematically examined Tim-3 expression in immune cells in mouse tumors and found that Tim-3 was specifically up-regulated in a large number of Treg, conventional CD4+, CD8+ T cells, dendritic cell 1 (DC1), and macrophage 1 (M1) in the tumor microenvironment (TME). Interestingly, Tim-3+ T cells in the TME were phenotypically effector but not “exhausted” T cells because Tim-3+ PD-1+ CD8+ T cells had a higher number of mitochondria, greater levels of glycolysis, and higher tumor-specific cytolytic activities compared to Tim-3− PD-1− CD8+ T cells. The combination treatment with Tim-3 and PD-1 mAbs resulted in a synergistic antitumor activity but also increased the expression of Lag-3 and GITR in TIL, demonstrating cross-regulation between multiple checkpoint molecules. Furthermore, we found that the antitumor efficacy with triple combination of Tim-3, PD-1, and Lag3 mAbs was much greater than any two antibodies. Mechanistically, we demonstrated that simultaneous targeting of Tim-3, PD-1, and Lag-3 cooperatively increased the levels of granzyme B and tumor-specific cytolytic activities of CD8+ TIL. Our data indicate that multiple checkpoint molecules are coordinately upregulated to inhibit the function of hyperactivated T cells in the TME and requirement for the simultaneous blockade of PD-1, Tim-3 and Lag3 for cancer treatment.

The governments of most countries are striving to coordinate residents’ housing demands with the supply of land to achieve high-quality urbanization and improve residents’ welfare. Based on the panel data of all Chinese provinces from 2010 to 2017, this study obtains 248 observations. It uses the coupling coordination degree, the Mann–Kendall trend test, and spatial autocorrelation methods to analyze the temporal and spatial variation of the coordination degree of population urbanization and affordable housing land supply. The study aims to clarify the temporal trend further and identify the spatial mismatch of affordable housing land resource allocation and apply a panel fixed model to determine its driving factors. The regional differentiation of the coordinated development level of population urbanization and affordable housing land in China’s provinces is apparent. The overall spatial distribution characteristics of coordination are opposite to the development of its economic level. The Mann–Kendall trend test indicated that the coupling coordination degree had a significant upward trend nationwide. Moreover, the coupling coordination degree shows a strong positive global spatial correlation. The local spatial agglomeration characteristics of the coordination are significant and primarily manifested in high–high and low–low agglomeration. A negative correlation exists between the degree of coupling coordination and the dependence of local governments on land finance and housing prices.

[This corrects the article DOI: 10.1371/journal.pgen.1007813.].

Abstract Background The bicomponent leukotoxins and the pyrogenic toxin superantigens (PTSAgs) are important virulence factors of Staphylococcus aureus. It is necessary to survey the prevalence and expression of these toxin-encoding genes for understanding the possible pathogenic capacity of S. aureus to cause disease. Methods Five leukotoxin genes and thirteen PTSAg determinants were detected for 177 S. aureus isolates from blood (n = 88) and wound (n = 89) infections by Polymerase Chain Reaction (PCR). The expression of leukotoxin ED (lukED) was determined by quantitative real-time PCR (qRT-PCR). The genetic backgrounds of isolates were analyzed by Staphylococcal Cassette Chromosome mec (SCCmec) typing (for methicillin-resistant S. aureus isolates), Pulsed-Field Gel Electrophoresis (PFGE), accessory gene regulator (agr) typing and Multilocus Sequence Typing (MLST, for representative isolates based on PFGE type) methods. Results 99.4% (176/177) isolates contained at least one of leukotoxin genes. Among them, 94.9% (168/177), 81.4% (144/177) and 67.8% (120/177) isolates harbored hlgBC, lukED and lukAB, respectively. Compared to leukotoxin genes, there was a relatively lower overall prevalence of PTSAg genes [99.4% versus 72.9% (129/177), P