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Abstract Background It is common knowledge that people’s intestinal microbiota is significantly influenced by the external environment. Although the Antarctic continent has been discovered for nearly 200 years, it is still unclear how this environment affects the human intestinal microbiota, especially that of the Chinese Han population. Methods Twelve explorers underwent a one-year Antarctic deployment from December 2017 to December 2018. The gut microbiota and clinical indexes at five time points, including two months (T1), five months (T2), eight months (T3), 11 months (T4) of residence in Antarctica and 7 months after returning to China (T5), were investigated. Results The intestinal microbiota of the participants was changed after one-year Antarctic deployment even after they left Antarctica. For the microbiota tested after returning to China (T5), the amount of Citrobacter, Akkermansia and conditional pathogens such as Escherichia-Shigella increased significantly (P

Abstract Background This study aims to review the clinical characteristics, therapeutic response and outcome of idiopathic pulmonary hemosiderosis (IPH), and discover the risk factors for recurrence in children with IPH, which will be helpful for the early diagnosis and reasonable treatment of this disease. Methods Children with a diagnosis of IPH were enrolled in the study. Clinical data of the children were collected and analysed. Results A total of 32 patients with regular follow-up after diagnosis were included in this study. Anaemia, cough and haemoptysis constituted the most common initial symptoms of the disease, and the incidences were 90.6%, 75% and 56.2%, respectively. The mean gap between the onset of symptoms and diagnosis was 5 (0.25-36) months. Most of the children experienced remission (complete and partial remission) over the course of 6 months of treatment, but 19 of the children experienced relapse. The causes of disease recurrence included respiratory tract infection (37.5%), corticosteroid (CS) reduction (18.8%), and irregular medication (6.3%). Interestingly, we found that children with history of allergy (HR 4.255, 1.107–16.356) tended to experience disease recurrence (p = 0.01). Conclusions Cough and anaemia are the most common symptoms in children with IPH. The recurrence rate of this disease is high, and respiratory tract infection is the most common cause of its recurrence. High-dose CS impluse therapy cannot reduce the recurrence rate of the disease. Allergic history was an import factor associated with disease recurrence. Trial registration This study is a retrospective and observational study, which does not involve human specimens or clinical intervention. Therefore, clinical trial registration is not required, and there is no clinical trial number. However, the study was approved by the Institutional Review Board/Ethics Committee affiliated with West China Second University Hospital, Sichuan University (Ethics review number 2022074).

Abstract Background The prognosis of breast cancer patients with visceral metastasis (VM) is significantly worse than that of patients without VM. We aimed to evaluate EZH2 (enhancer of zeste homolog 2) mutation as a biomarker associated with VM. Methods Data from forty-nine patients with metastatic breast cancer (MBC) pathologically confirmed at our hospital between March 2016 and September 2018 were collected. Metastatic tissue samples were obtained via ultrasound-guided needle biopsy, and paired peripheral blood samples were also collected. Tissue and blood samples were subjected to targeted next-generation sequencing via a 247-gene panel. Stably transfected MDA-MB-231 cells expressing wild-type EZH2 (EZH2WT) or a mutant form of EZH2 (EZH2K515R) were generated. Cell proliferation, colony formation ability, migration and invasion abilities and apoptosis were assessed using CCK-8 assays, plate colony formation assays, Transwell chamber assays and flow cytometry. Results The incidence of EZH2 mutations in the VM subgroup was greater than that in the non-VM subgroup in the entire cohort (n = 49, 42.3% vs. 13.0%, p = 0.024) and in the triple-negative breast cancer (TNBC) subgroup (n = 20, 50.0% vs. 10.0%, p = 0.05). Patients carrying EZH2 mutations had a significantly greater risk of developing VM than did those in the non-EZH2 mutation group in the entire cohort (HR 2.9) and in the TNBC subgroup (HR 6.45). Multivariate analysis revealed that EZH2 mutation was an independent prognostic factor for VM (HR 2.99, p = 0.009) in the entire cohort and in the TNBC subgroup (HR 10.1, p = 0.006). Data from cBioPortal also showed that patients with EZH2 mutations had a significantly greater risk of developing VM (HR 3.1), and the time to develop VM was significantly earlier in the EZH2 mutation group (31.5 months vs. 109.7 months, p = 0.008). Multivariate analysis revealed that EZH2 mutation (HR 2.73, p = 0.026) was an independent factor for VM after breast cancer surgery. There was no correlation between EZH2 mutations and BRCA1/2 mutations. Most of the patients (81.8%) in our cohort who developed VM carried the “c.1544A > G (p.K515R)” mutation. Compared with EZH2WT MDA-MB-231 cells, EZH2K515R MDA-MB-231 cells had greater colony formation rates (p

Abstract Background At present, preterm infants with respiratory distress syndrome (RDS) in China present higher mortality and morbidity rates than those in high-income countries. The aim of this nationwide survey was to assess the clinical management of RDS in China. Methods A nationwide cross-sectional survey to assess adherence to RDS management recommendations was performed. One neonatologist per hospital was randomly selected. The primary outcome was the key care of RDS management. Results Among the 394 participating hospitals, 88·3% were birthing centres. The number of doctors and nurses per bed were 0·27 and 0·72, respectively. Antenatal corticosteroids (any dose) were administered to 90% of the women at risk of preterm birth at 32 weeks. T-piece resuscitators were available in 77·8% of delivery rooms (DRs) (tertiary hospitals: 82·5% vs. secondary hospitals: 63·0%, p

Abstract Background The COVID-19 pandemic has underscored the critical role of sequencing technology in disease control and outbreak response. However, resource limitations and challenging environments often impede such efforts in low and middle-income countries. This study aimed to investigate the spectrum of viral co-infections, particularly with human viral pathogens, in SARS-CoV-2 positive individuals in Sierra Leone using metagenomic sequencing, evaluating the feasibility of utilizing this technology for epidemiological and evolutionary surveillance of pathogens related to public health in low-income environments. Methods We retrospectively collected and analyzed 98 nasopharyngeal swab specimens from SARS-CoV-2 positive individuals in Sierra Leone. Samples were pre-processed locally and transferred to China via FTA cards for metagenomic sequencing, which was performed using the Novaseq platform. The study focused on the identification of nasopharyngeal viruses co-infecting with SARS-CoV-2, with a deeper analysis of significant human viral pathogens such as HPV. Results The study identified 22 viral taxa from 20 families, including 4 human viruses. Notably, 19.4% of samples showed HPV co-infection with 34 distinct types, predominantly beta and gamma HPVs. Multiple HPV types were found in individual samples, indicating a high complexity of viral co-infections. Conclusions The identification of a wide range of co-infecting viruses, particularly multiple HPV genotypes, highlights the complexity of viral interactions and their potential implications for public health. These findings enhance our understanding of viral co-infections and provide valuable insights for public health interventions in Sierra Leone. Further research is needed to explore the clinical significance of these findings and their impact on disease outcomes.

Abstract DNA damage is a key factor affecting gametogenesis and embryo development. The integrity and stability of DNA are fundamental to a woman’s successful conception, embryonic development, pregnancy and the production of healthy offspring. Aging, reactive oxygen species, radiation therapy, and chemotherapy often induce oocyte DNA damage, diminished ovarian reserve, and infertility in women. With the increase of infertility population, there is an increasing need to study the relationship between infertility related diseases and DNA damage and repair. Researchers have tried various methods to reduce DNA damage in oocytes and enhance their DNA repair capabilities in an attempt to protect oocytes. In this review, we summarize recent advances in the DNA damage response mechanisms in infertility diseases such as PCOS, endometriosis, diminished ovarian reserve and hydrosalpinx, which has important implications for fertility preservation.

Abstract Adverse events (AEs) are a significant concern for healthcare systems. However, it is difficult to evaluate their influence because of the complexity of various medical services. This study aimed to assess the influence of AEs on the outcomes of hospitalized patients using a diagnosis-related group (DRG) database. We conducted a case–control study of hospitalized patients at a multi-district tertiary hospital with 2200 beds in China, using data from a DRG database. An AE refers to an unintended physical injury caused or contributed to by medical care that requires additional hospitalization, monitoring, treatment, or even death. Relative weight (RW), a specific indicator of DRG, was used to measure the difficulty of diagnosis and treatment, disease severity, and medical resources utilized. The primary outcomes were hospital length of stay (LOS) and hospitalization costs. The secondary outcome was discharge to home. This study applied DRG-based matching, Hodges–Lehmann estimate, regression analysis, and subgroup analysis to evaluate the influence of AEs on outcomes. Two sensitivity analyses by excluding short LOS and changing adjustment factors were performed to assess the robustness of the results. We identified 2690 hospitalized patients who had been divided into 329 DRGs, including 1345 patients who experienced AEs (case group) and 1345 DRG-matched normal controls. The Hodges–Lehmann estimate and generalized linear regression analysis showed AEs led to prolonged LOS (unadjusted difference, 7 days, 95% confidence interval [CI] 6–8 days; adjusted difference, 8.31 days, 95% CI 7.16–9.52 days) and excess hospitalization costs (unadjusted difference, $2186.40, 95% CI: $1836.87-$2559.16; adjusted difference, $2822.67, 95% CI: $2351.25-$3334.88). Logistic regression analysis showed AEs were associated with lower odds of discharge to home (unadjusted odds ratio [OR] 0.66, 95% CI 0.54–0.82; adjusted OR 0.75, 95% CI 0.61–0.93). The subgroup analyses showed that the results for each subgroup were largely consistent. LOS and hospitalization costs increased significantly after AEs in complex diseases (RW ≥ 2) and in relation to high degrees of harm subgroups (moderate harm and above groups). Similar results were obtained in sensitivity analyses. The burden of AEs, especially those related to complex diseases and severe harm, is significant in China. The DRG database serves as a valuable source of information that can be utilized for the evaluation and management of AEs.

Abstract Purpose To investigate the prevalence of insomnia among nurses with long COVID-19, analyze the potential risk factors and establish a nomogram model. Methods Nurses in Ningbo, China, were recruited for this study. General demographic information and insomnia, burnout, and stress assessment scores were collected through a face-to face questionnaire survey administered at a single center from March to May 2023. We used LASSO regression to identify potential factors contributing to insomnia. Then, a nomogram was plotted based on the model chosen to visualize the results and evaluated by receiver operating characteristic curves and calibration curves. Results A total of 437 nurses were recruited. 54% of the nurses had insomnia according to the Insomnia Severity Index (ISI) score. Eleven variables, including family structure, years of work experience, relaxation time, respiratory system sequelae, nervous system sequelae, others sequelae, attitudes toward COVID-19, sleep duration before infection, previous sleep problems, stress, and job burnout, were independently associated with insomnia. The R-squared value was 0.464, and the area under the curve was 0.866. The derived nomogram showed that neurological sequelae, stress, job burnout, sleep duration before infection, and previous sleep problems contributed the most to insomnia. The calibration curves showed significant agreement between the nomogram models and actual observations. Conclusion This study focused on insomnia among nurses with long COVID-19 and identified eleven risk factors related to nurses’ insomnia. A nomogram model was established to illustrate and visualize these factors, which will be instrumental in future research for identifying nurses with insomnia amid pandemic normalization and may increase awareness of the health status of healthcare workers with long COVID-19.

Abstract The reconstruction of critical-size calvarial defects remains a fundamental challenge. Recombinant collagen has gained significant attention in bone tissue engineering owing to its remarkable bioactivity and non-immunogenicity. Herein, we have for the first time developed a bioactive poly(ethylene glycol)-chondroitin sulfate-triple helical recombinant collagen (PEG-ChS-THRC) hydrogel for enhanced bone regeneration in cranial defects. A simple and mild crosslinking reaction of two-arm polyethylene glycol active ester (NHS-PEG-NHS), adipic dihydrazide modified chondroitin sulfate (ChS-ADH) and triple helical recombinant collagen (THRC) leads to the formation of the PEG-ChS-THRC hydrogel. The hydrogel demonstrates interconnected porous structures, enhanced mechanical strength, diminished swelling ratios and adjustable biodegradability. It possesses exceptional biocompatibility and bioactivity, significantly facilitating cell proliferation, adhesion, migration, and osteogenic differentiation of BMSCs. Micro-computed tomography (micro-CT), magnetic resonance imaging (MRI) and histological characterization of rat models with critical-size cranial defects have consistently demonstrated that the PEG-ChS-THRC hydrogel significantly promotes bone tissues regeneration. The innovative bioactive scaffold provides a remarkably improved remedy for critical-size cranial defects, holding greatly promising applications in the fields of bone tissue regeneration. Graphical Abstract

The bacterial communities in rhizosphere soil interact with the roots of plants. This interaction is beneficial for both the bacteria and the plants, which makes it very important to identify the structure of these bacterial communities for plant growth and development. However, the composition characteristics of bacterial communities in rhizosphere soil of 2-year and 5-year Haloxylon ammodendron have not been clearly defined. The purpose of this study was to identify the diverse composition of 2-year and 5-year Haloxylon ammodendron in Turpan, Xinjiang. Thus, rhizosphere soil bacteria were analyzed by isolating, purifying, and identifying the species through high-throughput sequencing technology. The bacterial strains in the rhizosphere soil of Haloxylon ammodendron were isolated with the dilution coating method, resulting in 37 isolated strains. The selective media were used to screen the growth-promoting characteristics of the rhizosphere soil isolates of Haloxylon ammodendron. The results of high-throughput amplification sequencing showed that the rhizosphere bacteria in the 2-year rhizosphere soil belonged to 45 phyla, 109 classes, 288 orders, 451 families, 826 genera, and 404 species, and those in the 5-year rhizosphere soil belonged to 56 phyla, 148 classes, 369 orders, 601 families, 1062 genera, and 671 species. Among them, Firmicutes, Proteobacteria, Actinobacteriota, Bacteroidota, Crenarchaeota, and so on are the dominant bacteria. There were 12206 and 14,053 OTUs in the 2-year-old and 5-year-old rhizosphere soil bacteria, respectively, and 3329 OTUs in the 2-year- and 5-year-old rhizosphere soil, accounting for 16.98% of the total number of OTUs. The results showed that three strains, sg16, sg21, and ss4, had the highest inorganic phosphorus solubility index (1.58). The isolated strain did not have the ability to dissolve organophosphorus and potassium, while the screened strain sg16 had the ability to fix nitrogen. Two strains with a good iron-bearing capacity, Sg9F and Sg1, were screened, among which Sg9F had the highest D/d value and Sg9F had the strongest iron-bearing capacity. The results showed that 37 strains of rhizosphere soil bacteria belonged to six genera. They are Bacillus, Corynebacterium, Phyllobacterium, Lysinibacillus, Sinorhizobium meliloti, and Streptomyces levis. Among them are sg21 (Bacillus sp.), sg1 (Bacillus sp.), sg9F (Streptomyces levis), sg16 (Phyllobacterium phragmitis), and ss4 (Sinorhizobium meliloti). This study provides a particular research basis for the influence of Haloxylon ammodendron rhizosphere bacteria on soil nutrient release and depicts a solution for improving the yield and quality of cistanche deserticola indirectly through isolating, screening, and identifying rhizosphere soil bacteria, including screening strains with growth-promoting functions and analyzing the population structure of rhizosphere bacteria in 2- and 5-year soil in combination with high-throughput sequencing technology.

Sweet cherry (Prunus avium) is one of the economically valuable horticultural fruit trees and it is widely cultivated throughout the world. Whirly (WHY) genes are a unique gene family with few members and have important biological functions in plant growth, development, and response to abiotic stress. This study utilized whole-genome identification to conduct a comprehensive analysis of the WHY genes in sweet cherry and examined their transcription levels in different tissues and under abiotic stress to explore their functions. Two WHY genes were identified in the sweet cherry genome and named PavWHY1 and PavWHY2, respectively, based on their homology with those in Arabidopsis thaliana. Both genes have theoretical isoelectric points greater than seven and are hydrophilic proteins, suggesting that they may be localized in plastids. The two genes are evolutionarily classified into two categories, with large differences in gene structure, and highly similar protein tertiary structures, and both have conserved domains of WHY. PavWHY1 and PavWHY2 are collinear with AtWHY1 and AtWHY2, respectively. The promoter sequence contains cis-acting elements related to hormones and abiotic stress, which are differentially expressed during flower bud differentiation, fruit development, and cold accumulation. qRT–PCR showed that PavWHY1 and PavWHY2 were differentially expressed in flower and fruit development and responded to low temperature and exogenous ABA treatment. The recombinant plasmid pGreenII-0800-Luc with the promoters of these two genes can activate luciferase expression in tobacco. Protein interaction predictions indicate that these gene products may interact with other proteins. This study reveals the molecular features, evolutionary relationships, and expression patterns of sweet cherry WHY genes, and investigates the activities of their promoters, which lays the foundation for further exploration of their biological functions and provides new insights into the WHY gene family in Rosaceae.

A case of bullous pilomatricoma is reported. A 22-year-old female had brown blue nodule on the right shoulder for 3 months and blisters for over 2 months. Dermatological examination revealed a demarcated 1.6 cm×1.0 cm×0.7 cm light purple semitranslucent bulla with loose wall and movable base on the right shoulder. A movable hard mass sized 0.4 cm×0.3 cm could be palpated. Histopathological examination of the lesion showed a mass with clear boundaries, and filtrates of basophils, transitional cells and shadow cells, along with proliferation and dilation of lymphatic vessels. The diagnosis was bullous pilomatricoma. Following surgical removal of the tumor, no recurrence was observed during 6 months of follow-up.

Abstract Background The presence of depression related to an increased risk of all-cause and cardiovascular disease (CVD) mortality has been reported. However, studies conducted on certain specific depressive symptoms are scarce. Our purpose was to assess the effect of both depressive symptoms scores and certain specific depressive symptoms on all-cause and CVD mortality. Methods In the present cohort study, all participants, aged 18 years or older, were enrolled in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2014. Depressive symptoms score was assessed using the validated 9-item Patient Health Questionnaire Depression Scale (PHQ-9), which ranges from 0 to 27, with a PHQ-9 score ≥ 10 diagnosed as depression. The outcome events were all-cause and CVD mortality, which were followed up from 2005 to 2014. The associations of both depressive symptoms score and certain specific depressive symptoms with all-cause and CVD mortality were examined by weighted multivariable proportional hazards models. Results A total of 26,028 participants aged ≥ 18 years were included in the statistical analysis, including 12,813 (49.2%) males and 13,215 (50.8%) females, with a mean (SD) age of 47.34 (18.86) years. During the 9.32 (3.20) years of mean (SD) follow-up, 3261 deaths were recorded, of which 826 were cardiovascular deaths. All-cause mortality was 16.87/1000 person-years in subjects with depression. In terms of CVD mortality, these figures were 4.53/1000 person-years. In the full model (model 3), elevated depressive symptoms scores were independently associated with an increased risk of all-cause mortality (Highest depression symptom score group: adjusted hazard ratio, 1.63; 95% CI 1.44–1.85) and CVD mortality (Highest depression symptom score group: adjusted hazard ratio, 1.73; 95% CI 1.34–2.24). All 9 specific depressive symptoms that make up the PHQ-9 were related to an increased risk of all-cause mortality. However, only 3 symptoms, including trouble sleeping or sleeping too much, poor appetite or overeating, and suicidal ideation, were no significantly associated with an increased risk of CVD mortality. Conclusions The elevated depressive symptoms scores were strongly associated with an increased risk of all-cause and CVD mortality in US adults. Furthermore, all 9 specific depressive symptoms were associated with high all-cause mortality. However, trouble sleeping or sleeping too much, poor appetite or overeating, and suicidal ideation might not increase the risk of CVD mortality.

Abstract Purpose To evaluate the availability, cost, affordability of anti-cancer medicines in Nanjing, Jiangsu. Methods A longitudinal tracking investigation study was performed to collect information about 24 essential anti-cancer medicines (EAMs) and 17 innovative anti-cancer medicines (IAMs) in 26 healthcare institutions in Nanjing from 2016 to 2020. The availability, cost, drug utilization and affordability of EAMs and IAMs were investigated. Results The availability of EAMs showed no significant changes in Nanjing, but the availability of IAMs showed a significant increase in 2018 and 2019 and tended to stabilize in 2020. For EAMs, the DDDc(Defined Daily Dose cost) of LPGs (Lowest-Priced Generics) showed no significant changes, and the DDDc of OBs (Originator Brands) and IAMs significantly decreased. The DDDs(Defined Daily Doses) of EAMs (LPGs) showed a decreasing trend since 2016 and rose again in 2019. Overall, the DDDs of EAMs (LPGs) decreased by 25.18% between 2016 and 2020, but the proportion selected for clinical treatment remained at 67.35% in 2020. The DDDs of EAMs (OBs) and IAMs both showed an increasing trend year by year, with a proportional increase of 207.72% and 652.68%, respectively; but the proportion selected for clinical treatment was only 16.09% and 16.56% respectively in 2020. EAMs (LPGs) had good affordability for urban residents but poor affordability for rural residents; the affordability of EAMs (OBs) and IAMs was poor for both urban and rural residents. Conclusions There were no significant changes in the availability and cost of EAMs (LPGs), whose lower prices showed better affordability. Although their relative change in drug utilization showed a decreasing trend, they still dominated clinical treatment. Driven by the national drug price negotiation (NDPN) policy, the availability of IAMs was on the rise. It is necessary to further develop and strengthen policies for essential medicines procurement assessment to improve the accessibility of EAMs.

Abstract Ziziphi Spinosae Semen (ZSS) is the first choice for the treatment of insomnia. This research aimed to reveal the spatial distribution of identifying quality markers of ZSS and to illustrate the metabolite quality characteristics of this herbal medicine. Here, we performed a matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) in situ to detect and image 33 metabolites in ZSS, including three saponins, six flavonoids, four alkaloids, eight fatty acids, and 12 amino acids. The MALDI images of the metabolites clearly showed the heterogeneous spatial distribution in different regions of ZSS tissues, such as the cotyledon, endosperm, and radicle. The distribution area of two saponins, six flavonoids, and three alkaloids increased significantly after the fried processing of ZSS. Based on the ion images, samples with different processing technologies were distinguished unambiguously by the pattern recognition method of orthogonal partial least squares discrimination analysis (OPLS-DA). Simultaneously, 23 major influencing components exerting higher ion intensities were identified as the potential quality markers of ZSS. Results obtained in the current research demonstrate that the processing of ZSS changes its content and distribution of the medicinal components. The analysis of MALDI-MSI provides a novel MS-based molecular imaging approach to investigate and monitor traditional medicinal plants.

Highlights MXene sediments is innovatively used as photothermal material for seawater desalination. Inspired by the natural wood transpiration process, a 3D MXene sediment-based aerogel with vertically aligned channels is innovatively prepared as solar evaporator. With unique structure and composition, excellent photothermal conversion efficiency, evaporation rate, salt resistance, and resistance to biological/oil/special environments are achieved in practical desalination.

Abstract The concentration prediction of PM2.5 plays a vital role in controlling the air and improving the environment. This paper proposes a prediction model (namely EEMD-ALSTM) based on Ensemble Empirical Mode Decomposition (EEMD), Attention Mechanism and Long Short-Term Memory network (LSTM). Through the combination of decomposition and LSTM, attention mechanism is introduced to realize the prediction of PM2.5 concentration. The advantage of EEMD-ALSTM model is that it decomposes and combines the original data using the method of ensemble empirical mode decomposition, reduces the high nonlinearity of the original data, and Specially reintroduction the attention mechanism, which enhances the extraction and retention of data features by the model. Through experimental comparison, it was found that the EEMD-ALSTM model reduced its MAE and RMSE by about 15% while maintaining the same R2 correlation coefficient, and the stability of the model in the prediction process was also improved significantly.

Recently, the challenges pertaining to the recycling of metal-based electrode materials and the resulting environmental pollution have impeded the advancement of battery technology. Consequently, biomass-derived carbon materials, distinguished by their eco-friendliness and consistent performance, stand as a pivotal solution to this predicament. Researchers have made significant strides in the integration of porous carbon materials derived from biomass into battery systems. Nevertheless, these materials face issues such as limited efficiency, modest yields, and a complex fabrication process. This paper endeavors to summarize the recent advancements in the utilization of biomass-derived carbon materials within the realm of batteries, offering a comprehensive examination of their battery performance from three distinct perspectives: synthesis, structure, and application. We posit that composite materials composed of biomass-derived carbon align with the trajectory of future development and present extensive potential for application. Ultimately, we will expound upon our profound outlook regarding the furtherance of biomass-derived carbon materials.

Mechanical metamaterials signify a groundbreaking leap in material science and engineering. The intricate and experience-dependent design process poses a challenge in uncovering architectural material sequences with exceptional mechanical properties. This study introduces inverse-designed 3D sequential metamaterials with outstanding mechanical attributes, achieved through a novel computational framework. The explored sequences based on Schoen's I-graph–wrapped package (IWP) and Schwarz Primitive (Schwarz P) surpass the Hashin-Shtrikman upper bound of Young's modulus at relative densities of 0.24 and 0.43, outperforming previous records. Optimized Body-Centered-Cubic (BCC) truss-based sets outperform traditional ones by 72.7%. This innovative approach can be extended for metamaterial customization, involving the optimization of multi-directional Young's modulus, total stiffness, and the addition of isotropy constraints. The paper explores the characteristics and implications of this innovation, emphasizing the impact of geometric and topological variations on mechanical performance. These metamaterial sequences offer unparalleled adaptability, and hold significant potential in structural engineering and adaptive mechanical systems, opening avenues for technological advancements.

BackgroundTo clarify whether Vitamin D prevent the occurrence of type 2 diabetes mellitus (T2DM) and improve glucose control in T2DM patients, we conducted this umbrella review, taking into account the inconsistent results of existing Meta-analyses. We aim to reveal the causal relationship between Vitamin D and T2DM through summarizing Meta-analyses of observational studies, and clarify the improvement on glucose control in T2DM patients through summarizing Meta-analyses of RCT studies between Vitamin D supplementation and T2DM patients, especially in T2DM patients with Vitamin D deficiency.MethodsWe collected the Meta-analyses of observational studies and RCTs in PubMed, Scopus, Embase, Web of Science, and Cochrane.Results16 Meta-analyses (6 effect sizes for cohort studies and 10 effect sizes for RCTs) were included in the umbrella Meta-analyses. Random-effects model was carried out to calculate the pooled point estimates and their respective 95% confidence intervals (CI). The results revealed that lower 25(OH)D levels increased the risk of T2DM (Pooled ESRR = 1.34; 95%CI: 1.16, 1.53), Vitamin D supplementation ameliorated FBG (ES = −0.56; 95%CI: −1.00, −0.11), HbA1c (ES = −0.11; 95%CI: −0.20, −0.02), insulin (ES = −0.38; 95%CI: −0.59, −0.18) and HOMA-IR (ES = −0.37; 95%CI: −0.57, −0.16) in T2DM patients, especially in those with Vitamin D deficiency (FBG = −0.98; HbA1c = −0.27; HOMA-IR = −0.52).ConclusionThe present umbrella Meta-analyses demonstrates the potential benefits of higher serum Vitamin D levels and Vitamin D supplementation in reducing the development and symptoms of T2DM.

Background: Female vulvar lichen sclerosus (VLS) is a chronic inflammatory skin disease of the vulva and its etiology is unknown. The main clinical symptoms are itching, burning and dyspareunia, and there is a lack of effective treatment. Methods: Clinical and follow-up data of women with VLS who underwent 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) from January 2023 to December 2023 in the department of obstetrics and gynecology, Qilu Hospital of Shandong University, were retrospectively analyzed. According to the inclusion and exclusion criteria, 36 patients with VLS who received ineffective conventional treatment (intractable VLS) were enrolled. Objective signs and subjective symptoms of vulvar lesions were recorded before treatment and 6 months after the end of treatment according to corresponding scoring criteria. Quality of life was evaluated using the Dermatology Life Quality Index (DLQI). Results: All patients received six sessions of ALA-PDT treatment and follow-up visits. After ALA-PDT treatment, 24 of 36 (66.67 %) patients' itching symptoms completely disappeared, 10 of 36 (27.78 %) patients' itching symptoms were relieved from severe to mild, and only 2 of 36 (5.56 %) patients' symptoms were not significantly relieved. 16 of 36 (44.4 %) patients' itching symptoms completely disappeared, 9 of 36 (25 %) patients' itching symptoms were relieved from severe to mild, and only 2 of 36 (5.56 %) patients still had severe pain. Compared to 22 patients with dyspareunia before treatment, only 9 patients still had dyspareunia with varying degrees of dyspareunia relief after treatment. Clinical signs improved significantly in the patients after ALA-PDT treatment. The total scores of clinical signs were (5.31 ± 1.67 vs 3.67 ± 1.71) before and after treatment. All patients showed improvement in DLQI after treatment. The main side effects of ALA-PDT were pain, erythema and swelling which were transient and tolerable. All patients were “satisfied” or “very satisfied” with the results of the treatment. Conclusions: ALA-PDT is a safe and effective treatment for women with intractable vulva lichen sclerosus.

Osteoporosis becomes a global public health concern due to its rising prevalence and substantial impact on life quality. Salvia miltiorrhiza Bunge (Salviae Miltiorrhizae Radix et Rhizoma, SM) has been firstly recorded in Shen Nong’s Herbal Classic, and is frequently prescribed in conjunction with other herbs for the management of osteoporosis. This systematic review aims to comprehensively analyze the recent advances of SM on osteoporosis in traditional Chinese clinical uses and preclinical investigations. Literature encompassing pertinent studies were systematically retrieved across multiple databases, including the PubMed, Web of Science, Chinese National Knowledge Infrastructure, Chinese VIP Database, and Chinese Biomedical Literature Database. Original investigations spanning from February 2014 to March 2024, including traditional Chinese medicine (TCM) clinical trials and preclinical studies, were employed to analyze the effects and actions of SM on osteoporosis. Thirty-eight TCM clinical trials were identified to employ SM in combination with other herbs for the management of primary and secondary osteoporosis. The overall efficacy was between 77% and 96.67%. Forty preclinical studies were identified to investigate the effects and actions of SM and/or its ingredients on osteoporosis. The anti-osteoporosis actions of this herb may be attributed to inhibit osteoclastogenesis/bone resorption and promote osteoblastogenesis/osteogenesis. The ethanol extracts and its ingredients (tanshinones) inhibit osteoclastogenesis/bone resorption by inhibiting the MAPK/NF-κB/NFATc1 signaling pathway and cathepsin K-induced collagen degradation. Both ethanol extracts (tanshinones) and water extracts (Sal B and tanshinol) contribute to osteoblastogenesis by promoting osteogenesis and angiogenesis via activation of the Wnt/β-catenin/VEGF and ERK/TAZ pathways, and eliminating ROS production targeting Nrf2/ARE/HO-1 pathway. In conclusions, SM may offer a novel strategy for osteoporosis management. Well-designed clinical trials are still needed to evaluate the actions of this herb and its ingredients on bone remodeling.

Abstract Recently, metasurface‐based photodetectors (metaphotodetectors) have been developed and applied in various fields. Metasurfaces are artificial materials with unique properties that have emerged over the past decade, and photodetectors are powerful tools used to quantify incident electromagnetic wave information by measuring changes in the conductivity of irradiated materials. Through an efficient microstructural design, metasurfaces can effectively regulate numerous characteristics of electromagnetic waves and have demonstrated unique advantages in various fields, including holographic projection, stealth, biological image enhancement, biological sensing, and energy absorption applications. Photodetectors play a crucial role in military and civilian applications; therefore, efficient photodetectors are essential for optical communications, imaging technology, and spectral analysis. Metaphotodetectors have considerably improved sensitivity and noise‐equivalent power and miniaturization over conventional photodetectors. This review summarizes the advantages of metaphotodetectors based on five aspects. Furthermore, the applications of metaphotodetectors in various fields including military and civil applications, are systematically discussed. It highlights the potential future applications and developmental trends of metasurfaces in metaphotodetectors, provides systematic guidance for their development, and establishes metasurfaces as a promising technology.

BackgroundThe causal relationship between gut microbiota and insulin-like growth factor 1 (IGF-1) remains unclear. The purpose of this study was to explore the causal relationship between gut microbiota and IGF-1 in men and women.MethodsSingle-nucleotide polymorphisms (SNPs) related to gut microbiota were derived from pooled statistics from large genome-wide association studies (GWASs) published by the MiBioGen consortium. Pooled data for IGF-1 were obtained from a large published GWAS. We conducted Mendelian randomization (MR) analysis, primarily using the inverse variance weighted (IVW) method. Additionally, we performed sensitivity analyses to enhance the robustness of our results, focusing on assessing heterogeneity and pleiotropy.ResultsIn forward MR analysis, 11 bacterial taxa were found to have a causal effect on IGF-1 in men; 14 bacterial taxa were found to have a causal effect on IGF-1 in women (IVW, all P < 0.05). After false discovery rate (FDR) correction, all bacterial traits failed to pass the FDR correction. In reverse MR analysis, IGF-1 had a causal effect on nine bacterial taxa in men and two bacterial taxa in women respectively (IVW, all P < 0.05). After FDR correction, the causal effect of IGF-1 on order Actinomycetales (PFDR= 0.049) remains in men. The robustness of the IVW results was further confirmed after heterogeneity and pleiotropy analysis.ConclusionOur study demonstrates a bidirectional causal link between the gut microbiota and IGF-1, in both men and women.

IntroductionCorm rot in saffron (Crocus sativus L.) significantly impacts yield and quality. Non-toxic fungi, particularly Trichoderma species, are valuable for biological control due to their production of diverse and biologically active secondary metabolites.MethodsThis study aimed to isolate an effective antagonistic fungus against the pathogenic fungi causing corm rot in saffron. Four pathogenic fungi (Fusarium oxysporum, Fusarium solani, Penicillium citreosulfuratum, and Penicillium citrinum) were isolated from diseased saffron bulbs in Chongming. Initial screening through dual culture with these pathogens re-screening from rhizosphere soil samples of C. sativus based on its inhibitory effects through volatile, nonvolatile, and fermentation broth metabolites. The inhibitory effect of biocontrol fungi on pathogenic fungi in vitro was evaluated by morphological observation and molecular biology methods.ResultsAntagonistic fungi were identified as Trichoderma brevicompactum DTN19. F. oxysporum was identified as the most severe pathogen. SEM (scanning electron microscope) and TEM (transmission electron microscope) observations revealed that T. brevicompactum DTN19 significantly inhibited the growth and development of F. oxysporum mycelium, disrupting its physiological structure and spore formation. Additionally, T. brevicompactum DTN19 demonstrated nitrogen fixation and production of cellulase, IAA (Indole acetic acid), and siderophores. Whole-genome sequencing of strain DTN19 revealed genes encoding protease, cellulase, chitinase, β-glucosidase, siderophore, nitrogen cycle, and sulfate transporter-related proteinsDiscussionT. brevicompactum DTN19 may inhibit the propagation of pathogenic fungi by destroying their cell walls or producing antibiotics. It can also produce IAA and iron carriers, which have the potential to promote plant growth. Overall, T. brevicompactum DTN19 showed the development prospect of biological agents.

Ovaries are essential for healthy female reproduction, with the follicles as their fundamental functional units, which consist of an oocyte and surrounding granulosa cells. The development and formation of follicles in the ovaries are closely linked to reproductive health. Oxylipins refer to oxidative metabolites produced from the oxidation of polyunsaturated fatty acids, either through automatic oxidation or with the help of specific enzymes. They play crucial regulatory roles in the immune system, oxidative stress, and inflammatory reactions and are intimately linked to the development of numerous illnesses, such as diabetes, heart disease, asthma, and Alzheimer’s disease. Furthermore, oxylipins have a complex relationship with ovarian function, and both prostaglandins and leukotrienes produced by arachidonic acid affect processes such as follicle growth and development, ovulation, and hormone regulation. The synthesis and metabolism of oxylipins in the ovaries are finely regulated. Oxylipin dysregulation has been linked to various ovarian diseases, including endometriosis, polycystic ovary syndrome, ovarian cancer, and premature ovarian insufficiency. In addition, potential therapeutic targets and interventions targeting the oxylipin pathway for the treatment of ovarian diseases have become a prominent research focus, including regulating the enzymes responsible for oxylipin synthesis, using anti-inflammatory agents, and regulating lipid metabolism. Recent research has been directed towards improving the reproductive outcomes of women with ovarian diseases through this series of interventions. An overview of the role of oxylipins in ovarian function and disease is provided in this article, which will aid researchers in understanding the current state of the field and in identifying future directions.

Viral vectors are agents enabling gene transfer and genome editing and have widespread utility across the healthcare and biotechnology sectors. In January 2023, the International Bureau for Weights and Measures’ Consultative Committee for Amount of Substance (CCQM) held a workshop on Metrology for Viral systems as molecular tools. The workshop brought together international leaders from across regulatory, industry, government science, and metrology sectors to better understand key challenges for the community: Exploring current limitations in the measurement of virus-derived, virus-based, and virus-like systems in terms of quantification and characterisation; surveying the state-of-the-art in analytical methods and reference material provision for these entities; and initiating a dialog for the strategic development and implementation of suitable standardisation approaches for this sector. This article presents the workshop background and rationale, presentation summaries, conclusions, and recommendations.

Abstract Near-infrared (NIR) hyperspectral imaging is a powerful technique that enables the capture of three-dimensional (3D) spectra-spatial information within the NIR spectral range, offering a wide array of applications. However, the high cost associated with InGaAs focal plane array (FPA) has impeded the widespread adoption of NIR hyperspectral imaging. Addressing this challenge, in this study, we adopt an alternative approach—single-pixel detection for NIR hyperspectral imaging. Our investigation reveals that single-pixel detection outperforms conventional FPA, delivering a superior signal-to-noise ratio (SNR) for both spectral and imaging reconstruction. To implement this strategy, we leverage self-assembled colloidal quantum dots (CQDs) and a digital micromirror device (DMD) for NIR spectral and spatial information multiplexing, complemented by single-pixel detection for simultaneous spectral and image reconstruction. Our experimental results demonstrate successful NIR hyperspectral imaging with a detection window about 600 nm and an average spectral resolution of 8.6 nm with a pixel resolution of 128 × 128. The resulting spectral and spatial data align well with reference instruments, which validates the effectiveness of our approach. By circumventing the need for expensive and bulky FPA and wavelength selection components, our solution shows promise in advancing affordable and accessible NIR hyperspectral imaging technologies, thereby expanding the range of potential applications.

Abstract High-altitude cerebral edema (HACE) is a severe neurological condition that can occur at high altitudes. It is characterized by the accumulation of fluid in the brain, leading to a range of symptoms, including severe headache, confusion, loss of coordination, and even coma and death. Exosomes play a crucial role in intercellular communication, and their contents have been found to change in various diseases. This study analyzed the metabolomic characteristics of blood exosomes from HACE patients compared to those from healthy controls (HCs) with the aim of identifying specific metabolites or metabolic pathways associated with the development of HACE conditions. A total of 21 HACE patients and 21 healthy controls were recruited for this study. Comprehensive metabolomic profiling of the serum exosome samples was conducted using ultraperformance liquid chromatography–tandem mass spectrometry (UPLC‒MS/MS). Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed to identify the metabolic pathways affected in HACE patients. Twenty-six metabolites, including ( +)-camphoric acid, choline, adenosine, adenosine 5′-monophosphate, deoxyguanosine 5′-monophosphate, guanosine, and hypoxanthine-9-β-D-arabinofuranoside, among others, exhibited significant changes in expression in HACE patients compared to HCs. Additionally, these differentially abundant metabolites were confirmed to be potential biomarkers for HACE. KEGG pathway enrichment analysis revealed several pathways that significantly affect energy metabolism regulation (such as purine metabolism, thermogenesis, and nucleotide metabolism), estrogen-related pathways (the estrogen signaling pathway, GnRH signaling pathway, and GnRH pathway), cyclic nucleotide signaling pathways (the cGMP-PKG signaling pathway and cAMP signaling pathway), and hormone synthesis and secretion pathways (renin secretion, parathyroid hormone synthesis, secretion and action, and aldosterone synthesis and secretion). In patients with HACE, adenosine, guanosine, and hypoxanthine-9-β-D-arabinofuranoside were negatively correlated with height. Deoxyguanosine 5′-monophosphate is negatively correlated with weight and BMI. Additionally, LPE (18:2/0:0) and pregnanetriol were positively correlated with age. This study identified potential biomarkers for HACE and provided valuable insights into the underlying metabolic mechanisms of this disease. These findings may lead to potential targets for early diagnosis and therapeutic intervention in HACE patients.

Abstract While many studies have examined the role of biochar in carbon (C) accrual in short-term scale, few have explored the decadal scale influences of biochar on non-biochar C, e.g., native soil organic C (SOC) and added substrate. To address this knowledge gap, soils were collected from decade-old biochar field trials located in the United Kingdom (Cambisol) and China (Fluvisol), with each site having had three application rates (25–30, 50–60 and 75–100 Mg ha−1) of biochar plus an unamended Control, applied once in 2009. We assessed physicochemical and microbial properties associated with sucrose (representing the rhizodeposits) mineralization and the priming effect (PE) on native SOC. Here, we showed both soils amended with biochar at the middle application rate (50 Mg ha−1 biochar in Cambisol and 60 Mg ha−1 biochar in Fluvisol) resulted in greater substrate mineralization. The enhanced accessibility and availability of sucrose to microorganisms, particularly fast-growing bacterial genera like Arenimonas , Spingomonas, and Paenibacillus (r-strategists belonging to the Proteobacteria and Firmicutes phyla, respectively), can be attributed to the improved physicochemical properties of the soil, including pH, porosity, and pore connectivity, as revealed by synchrotron-based micro-CT. Random forest analysis also confirmed the contribution of the microbial diversity and physical properties such as porosity on sucrose mineralization. Biochar at the middle application rate, however, resulted in the lowest PE (0.3 and 0.4 mg of CO2-C g soil−1 in Cambisol and Fluvisol, respectively) after 53 days of incubation. This result might be associated with the fact that the biochar promoted large aggregates formation, which enclosed native SOC in soil macro-aggregates (2–0.25 mm). Our study revealed a diverging pattern between substrate mineralization and SOC priming linked to the biochar application rate. This suggests distinct mechanisms, biophysical and physicochemical, driving the mineralization of non-biochar carbon in a field where biochar was applied a decade before.

Abstract Background Head and neck squamous cell carcinoma (HNSCC) is a prevalent cancer with a poor survival rate due to anatomical limitations of the head and a lack of reliable biomarkers. Cuproptosis represents a novel cellular regulated death pathway, and N6-methyladenosine (m6A) is the most common internal RNA modification in mRNA. They are intricately connected to tumor formation, progression, and prognosis. This study aimed to construct a risk model for HNSCC using a set of mRNAs associated with m6A regulators and cuproptosis genes (mcrmRNA). Methods RNA-seq and clinical data of HNSCC patients from The Cancer Genome Atlas (TCGA) database were analyzed to develop a risk model through the least absolute shrinkage and selection operator (LASSO) analysis. Survival analysis and receiver operating characteristic (ROC) analysis were performed for the high- and low-risk groups. Additionally, the model was validated using the GSE41613 dataset from the Gene Expression Omnibus (GEO) database. GSEA and CIBERSORT were applied to investigate the immune microenvironment of HNSCC. Results A risk model consisting of 32 mcrmRNA was developed using the LASSO analysis. The risk score of patients was confirmed to be an independent prognostic indicator by multivariate Cox analysis. The high-risk group exhibited a higher tumor mutation burden. Additionally, CIBERSORT analysis indicated varying levels of immune cell infiltration between the two groups. Significant disparities in drug sensitivity to common medications were also observed. Enrichment analysis further unveiled significant differences in metabolic pathways and RNA processing between the two groups. Conclusions Our risk model can predict outcomes for HNSCC patients and offers valuable insights for personalized therapeutic approaches.

Abstract Background Sepsis is a severe form of systemic inflammatory response syndrome that is caused by infection. Sepsis is characterized by a marked state of stress, which manifests as nonspecific physiological and metabolic changes in response to the disease. Previous studies have indicated that the stress hyperglycemia ratio (SHR) can serve as a reliable predictor of adverse outcomes in various cardiovascular and cerebrovascular diseases. However, there is limited research on the relationship between the SHR and adverse outcomes in patients with infectious diseases, particularly in critically ill patients with sepsis. Therefore, this study aimed to explore the association between the SHR and adverse outcomes in critically ill patients with sepsis. Methods Clinical data from 2312 critically ill patients with sepsis were extracted from the MIMIC-IV (2.2) database. Based on the quartiles of the SHR, the study population was divided into four groups. The primary outcome was 28-day all-cause mortality, and the secondary outcome was in-hospital mortality. The relationship between the SHR and adverse outcomes was explored using restricted cubic splines, Cox proportional hazard regression, and Kaplan‒Meier curves. The predictive ability of the SHR was assessed using the Boruta algorithm, and a prediction model was established using machine learning algorithms. Results Data from 2312 patients who were diagnosed with sepsis were analyzed. Restricted cubic splines demonstrated a "U-shaped" association between the SHR and survival rate, indicating that an increase in the SHR is related to an increased risk of adverse events. A higher SHR was significantly associated with an increased risk of 28-day mortality and in-hospital mortality in patients with sepsis (HR > 1, P

Abstract Background Giant ovarian cysts (GOCs)complicated with progressive bulbar paralysis (PBP) are very rare, and no such literature about these cases have been reported. Through the diagnosis and treatment of this case, the perioperative related treatment of such patients was analyzed in detail, and early-stage ovarian mucinous carcinoma was unexpectedly found during the treatment, which provided reference for clinical diagnosis and treatment of this kind of diseases. Case presentation In this article, we reported a 38-year-old female patient. The patient was diagnosed with PBP 2 years ago. Examination revealed a large fluid-dominated cystic solid mass in the pelvis measuring approximately 28.6×14.2×8.0 cm. Carbohydrate antigen19-9(CA19-9) 29.20 IU/mL and no other significant abnormalities were observed. The patient eventually underwent transabdominal right adnexal resection under regional anesthesia, epidural block. Postoperative pathology showed mucinous carcinoma in some areas of the right ovary. The patient was staged as stage IA, and surveillance was chosen. With postoperative follow-up 1 month later, her CA19-9 decreased to 14.50 IU/ml. Conclusions GOCs combined with PBP patients require a multi-disciplinary treatment. Preoperative evaluation of the patient's PBP progression, selection of the surgical approach in relation to the patient's fertility requirements, the nature of the ovarian cyst and systemic condition are required. Early mucinous ovarian cancer accidentally discovered after operation and needs individualized treatment according to the guidelines and the patient's situation. The patient's dysphagia and respiratory function should be closely monitored during the perioperative period. In addition, moral support from the family is also very important.

Bread wheat (Triticum aestivum) is a staple food crop worldwide. The genetic dissection of important nutrient traits is essential for the biofortification of wheat to meet the nutritional needs of the world’s growing population. Here, 45,298 single-nucleotide polymorphisms (SNPs) from 55K chip arrays were used to genotype a panel of 768 wheat cultivars, and a total of 154 quantitative trait loci (QTLs) were detected for eight traits under three environments by genome-wide association study (GWAS). Three QTLs (qMn-3B.1, qFe-3B.4, and qSe-3B.1/qFe-3B.6) detected repetedly under different environments or traits were subjected to subsequent analyses based on linkage disequilibrium decay and the P-values of significant SNPs. Significant SNPs in the three QTL regions formed six haplotypes for qMn-3B.1, three haplotypes for qFe-3B.4, and three haplotypes for qSe-3B.1/qFe-3B.6. Phenotypic analysis revealed significant differences among haplotypes. These results indicated that the concentrations of several nutrient elements have been modified during the domestication of landraces to modern wheat. Based on the QTL regions, we identified 15 high-confidence genes, eight of which were stably expressed in different tissues and/or developmental stages. TraesCS3B02G046100 in qMn-3B.1 and TraesCS3B02G199500 in qSe-3B.1/qFe-3B.6 were both inferred to interact with metal ions according to the Gene Ontology (GO) analysis. TraesCS3B02G199000, which belongs to qSe-3B.1/qFe-3B.6, was determined to be a member of the WRKY gene family. Overall, this study provides several reliable QTLs that may significantly affect the concentrations of nutrient elements in wheat grain, and this information will facilitate the breeding of wheat cultivars with improved grain properties.

Abstract To investigate the predictive value of baseline platelet count and its short-term dynamic changes in the prognosis of patients with acute heart failure (AHF) in the intensive care unit. Patients diagnosed with AHF in the medical information mart for intensive care III and their clinical data were retrospectively filtered. Patients were divided into survivor and non-survivor groups based on their prognosis during hospitalization, and differences in baseline data between groups were compared. Logistic regression models and restricted cubic spline (RCS) plots were performed to evaluate the relationship between baseline platelet counts and in-hospital mortality. Changes and trends in platelet counts were compared between the survivor and non-survivor groups after adjusting for confounders with the generalized additive mixing model (GAMM). A total of 2930 critical patients with acute heart failure were included, of which 2720 were survivors and 210 were non-survivors. Multiple logistic regression models revealed that baseline platelet count was an independent factor in hospital mortality (OR 0.997, 95% CI 0.994–0.999, P-value = 0.018). The RCS plot demonstrated a U-shaped dose–response relationship between baseline platelet count and in-hospital mortality. GAMM analysis suggested that the platelet counts decreased and then increased in the survivor group and gradually decreased in the non-survivor group, with a gradual increase of difference between two groups. After adjusting for confounders, the mean daily increase was −6.014 (95% CI −7.076–4.953, P-value

Abstract Wilson’s disease is caused by abnormal copper metabolism resulting in deposition in various organs, including the brain, liver, and cornea, thus disrupting organ function. It is characterized by encephalopathy, extrapyramidal symptoms, progressive liver failure, and copper ring deposition in the cornea. Management of this disease should include quality of life maintenance; however, relevant studies on this topic are lacking. This study aimed to assess the factors affecting the quality of life (QoL) of patients with Wilson’s disease. A cross-sectional survey using convenience sampling was conducted between July 2020 and March 2021 at the hospital. Data on patient characteristics, 36-item Short-Form General Health Survey, Uniform Wilson Disease Rating Scale, and Hamilton Depression Rating Scale scores were collected. Associations among quality of life depression, anxiety, and Wilson’s disease progression were examined using Pearson correlation analysis. Factors affecting the quality of life of patients, including depression, anxiety, liver function, clinical symptoms, diet, liver function, brain magnetic resonance imaging (MRI) findings, disease duration, Barthel Index, and Morse scores were examined using multivariate linear regression analysis. This study included 134 patients with Wilson’s disease whose mean age was 29.12 ± 8.59 years. The mean QoL score in the patient group was 71.38 ± 9.55 points and was negatively correlated with anxiety (r = − 0.883, P = 0.000), depression (r = − 0.852 P = 0.000), and clinical symptoms (r = − 0.542, P = 0.000) scores. Anxiety, depression, and clinical symptoms severity are vital factors for the QoL of patients with Wilson’s disease. The study provides foundational evidence to design novel interventions, including symptom management, diet, and self-care ability, which can help in improving the quality of life in patients with Wilson’s disease and decreasing the burden associated with this disease.

Abstract One-unit-cell FeSe films on SrTiO3 substrates are of great interest owing to significantly enlarged pairing gaps characterized by two coherence peaks at ±10 meV and ±20 meV. In-situ transport measurement is desired to reveal novel properties. Here, we performed in-situ microscale electrical transport and combined scanning tunneling microscopy measurements on continuous one-unit-cell FeSe films with twin boundaries. We observed two spatially coexisting superconducting phases in domains and on boundaries, characterized by distinct superconducting gaps ( $${\Delta }_{1}$$ Δ 1 ~15 meV vs. $${\Delta }_{2}$$ Δ 2 ~10 meV) and pairing temperatures (T p1~52.0 K vs. T p2~37.3 K), and correspondingly two-step nonlinear $$V \sim {I}^{\alpha }$$ V ~ I α behavior but a concurrent Berezinskii–Kosterlitz–Thouless (BKT)-like transition occurring at $${T}_{{{{{{\rm{BKT}}}}}}}$$ T BKT ~28.7 K. Moreover, the onset transition temperature $${T}_{{{{{{\rm{c}}}}}}}^{{{{{{\rm{onset}}}}}}}$$ T c onset ~54 K and zero-resistivity temperature $${T}_{{{{{{\rm{c}}}}}}}^{{{{{{\rm{zero}}}}}}}$$ T c zero ~31 K are consistent with T p1 and $${T}_{{{{{{\rm{BKT}}}}}}}$$ T BKT , respectively. Our results indicate the broadened superconducting transition in FeSe/SrTiO3 is related to intrinsic electronic inhomogeneity due to distinct two-gap features and phase fluctuations of two-dimensional superconductivity.

Prior to entering the water body, microplastics (MPs) are mostly collected at the sewage treatment plant and the biological treatment unit is the sewage treatment facility's central processing unit. This review aims to present a comprehensive analysis of the detrimental impacts of MPs on the biological treatment unit of a sewage treatment plant and it covers how MPs harm the effluent quality of biological treatment processes. The structure of microbial communities is altered by MPs presence and additive release, which reduces functional microbial activity. Extracellular polymers, oxidative stress, and enzyme activity are explored as micro views on the harmful mechanism of MPs on microorganisms, examining the toxicity of additives released by MPs and the harm caused to microorganisms by harmful compounds that have been adsorbed in the aqueous environment. This article offers a theoretical framework for a thorough understanding of the potential problems posed by MPs in sewage treatment plants and suggests countermeasures to mitigate those risks to the aquatic environment. HIGHLIGHTS This paper provides a detailed overview of the toxic effects of microplastics (MPs) on biological treatment units.; Explored the toxic effects of MPs releasing additives and the harm of adsorbed toxic substances in the water environment to microorganisms.; Microscopic discussion on the influence mechanism of MPs on microorganisms in wastewater treatment plants.; Propose the potential threat of MPs in sewage treatment plants.;

Abstract The voltage-gated calcium channel CaV1.2 is essential for cardiac and vessel smooth muscle contractility and brain function. Accumulating evidence demonstrates that malfunctions of CaV1.2 are involved in brain and heart diseases. Pharmacological inhibition of CaV1.2 is therefore of therapeutic value. Here, we report cryo-EM structures of CaV1.2 in the absence or presence of the antirheumatic drug tetrandrine or antihypertensive drug benidipine. Tetrandrine acts as a pore blocker in a pocket composed of S6II, S6III, and S6IV helices and forms extensive hydrophobic interactions with CaV1.2. Our structure elucidates that benidipine is located in the DIII-DIV fenestration site. Its hydrophobic sidechain, phenylpiperidine, is positioned at the exterior of the pore domain and cradled within a hydrophobic pocket formed by S5DIII, S6DIII, and S6DIV helices, providing additional interactions to exert inhibitory effects on both L-type and T-type voltage gated calcium channels. These findings provide the structural foundation for the rational design and optimization of therapeutic inhibitors of voltage-gated calcium channels.

Abstract Facile and efficient photocatalysts using sunlight, as well as fast and sensitive surface-enhanced Raman spectroscopy (SERS) substrates, are urgently needed for practical degradation of tetracycline (TC). To meet these requirements, a new paradigm for PI/TiO2/Ag organic‒inorganic ternary flexible microfibers based on semiconducting titanium dioxide (TiO2), the noble metal silver (Ag) and the conjugated polymer polyimide (PI) was developed by engineering a simple method. Under sunlight, the photocatalytic characteristics of the PI/TiO2/Ag flexible microfibers containing varying amounts of Ag quantum dots (QDs) were evaluated with photocatalytic degradation of TC in aqueous solution. The results demonstrated that the amount of Ag affected the photocatalytic activity. Among the tested samples, PI/TiO2/Ag-0.07 (93.1%) exhibited a higher photocatalytic degradation rate than PI/TiO2 (25.7%), PI/TiO2/Ag-0.05 (77.7%), and PI/TiO2/Ag-0.09 (63.3%). This observation and evaluation conducted in the present work strongly indicated a charge transfer mechanism. Moreover, the PI/TiO2/Ag-0.07 flexible microfibers exhibited highly sensitive SERS detection, as demonstrated by the observation of the Raman peaks for TC even at an extremely low concentration of 10–10 moles per liter. The excellent photocatalytic performance and SERS detection capability of the PI/TiO2/Ag flexible microfibers arose from the Schottky barrier formed between Ag and TiO2 and also from the outstanding plasmonic resonance and visible light absorptivity of Ag, along with immobilization by the PI. The successful synthesis of PI/TiO2/Ag flexible microfibers holds significant promise for sensitive detection and efficient photocatalytic degradation of antibiotics.

The juvenile-to-adult phase change with first flowering as the indicator plays a crucial role in the lifecycle of fruit trees. However, the molecular mechanisms underlying phase change in fruit trees remain largely unknown. Shikimic acid (ShA) pathway is a main metabolic pathway closely related to the synthesis of hormones and many important secondary metabolites participating in plant phase change. So, whether ShA regulates phase change in plants is worth clarifying. Here, the distinct morphological characteristics and the underlying mechanisms of phase change in jujube (Ziziphus jujuba Mill.), an important fruit tree native to China with nutritious fruit and outstanding tolerance abiotic stresses, were clarified. A combined transcriptome and metabolome analysis found that ShA is positively involved in jujube (‘Yuhong’ × ‘Xing 16’) phase change. The genes in the upstream of ShA synthesis pathway (ZjDAHPS, ZjDHQS and ZjSDH), the contents of ShA and the downstream secondary metabolites like phenols were significantly upregulated in the phase change period. Further, the treatment of spraying exogenous ShA verified that ShA at a very low concentration (60 mg · L−1) can substantially speed up the phase change and flowering of jujube and other tested plants including Arabidopsis, tomato and wheat. The exogenous ShA (60 mg · L−1) treatment in jujube seedlings could increase the accumulation of endogenous ShA, enhance leaf photosynthesis and the synthesis of phenols especially flavonoids and phenolic acids, and promote the expression of genes (ZjCOs, ZjNFYs and ZjPHYs) involved in flowering pathway. Basing on above results, we put forward a propose for the underlying mechanism of ShA regulating phase change, and a hypothesis that ShA could be considered a phytohormone-like substance because it is endogenous, ubiquitous, movable and highly efficient at very low concentrations. This study highlights the critical role of ShA in plant phase change and its phytohormone-like properties.

Abstract Background Undernutrition (UN) is a critical public health issue that threatens the lives of children under five in developing countries. While evidence indicates the crucial role of the gut microbiome (GM) in UN pathogenesis, the strain-level inspection and bacterial co-occurrence network investigation in the GM of UN children are lacking. Results This study examines the strain compositions of the GM in 61 undernutrition patients (UN group) and 36 healthy children (HC group) and explores the topological features of GM co-occurrence networks using a complex network strategy. The strain-level annotation reveals that the differentially enriched species between the UN and HC groups are due to discriminated strain compositions. For example, Prevotella copri is mainly composed of P. copri ASM1680343v1 and P. copri ASM345920v1 in the HC group, but it is composed of P. copri ASM346549v1 and P. copri ASM347465v1 in the UN group. In addition, the UN-risk model constructed at the strain level demonstrates higher accuracy (AUC = 0.810) than that at the species level (AUC = 0.743). With complex network analysis, we further discovered that the UN group had a more complex GM co-occurrence network, with more hub bacteria and a higher clustering coefficient but lower information transfer efficiencies. Moreover, the results at the strain level suggested the inaccurate and even false conclusions obtained from species level analysis. Conclusions Overall, this study highlights the importance of examining the GM at the strain level and investigating bacterial co-occurrence networks to advance our knowledge of UN pathogenesis.

Citrobacter braakii (C. braakii) is an anaerobic, gram‐negative bacterium that has been isolated from the environment, food, and humans. Infection by C. braakii has been associated with acute mucosal inflammation in the intestine, respiratory tract, and urinary tract. However, the pathogenesis of C. braakii in the gastric mucosa has not yet been clarified. In this study, the bacterium was detected in 35.5% (61/172) of patients with chronic gastritis (CG) and was closely associated with the severity of mucosal inflammation. Citrobacter braakii P1 isolated from a patient with CG exhibited urease activity and acid resistance. It contained multiple secretion systems, including a complete type I secretion system (T1SS), T5aSS and T6SS. We then predicted the potential pilus‐related adhesins. Citrobacter braakii P1 diffusely adhered to AGS cells and significantly increased lactate dehydrogenase (LDH) release; the adhesion rate and LDH release were much lower in HEp‐2 cells. Strain P1 also induced markedly increased mRNA and protein expression of IL‐8 and TNF‐α in AGS cells, and the fold increase was much higher than that in HEp‐2 cells. Our results demonstrate proinflammatory and cytotoxic role of C. braakii in gastric epithelial cells, indicating the bacterium is potentially involved in inducing gastric mucosa inflammation.

Highland barley is the main food of Tibetan people, which is rich in starch, fat, protein, vitamins, dietary fiber, β-glucan, polyphenol, amino acid, etc. Highland barley has widely healthy functions such as hypolipidemic, hypoglycemic, cholesterol lowing, antioxidation, and gastrointestinal regulation, etc. Due to the special characteristics including bran thickness, taste bad, and indigestible of the crude material, as a result that highland barley could be edible after processing. Superheated steam, baking, frying, steaming, boiling, and other hot processing methods as well as germination are common processing methods for highland barley. Different processing steps of highland barley would have a certain impact on the contents and structures of its nutritional compositions, and the biological activities such as hypolipidemic and hypoglycemic are also varied. Therefore, this paper reviews the effects of different processing methods on nutrients and bioactivities of highland barley in recent 10 years, and its variable regular and influencing factors are also discussed. Finally, the development of functional food products of highland barley is prospected. It has certain reference value for the in-depth digging, quality improvement, technological innovation and new product development of highland barley.

TGF-β signaling pathway has been demonstrated to be closely related to chemoresistance, which is the major cause of recurrence and poor outcome in colorectal cancer (CRC), however, the comprehensive epigenetic landscape that functionally implicates in the regulation of TGF-β pathway-associated chemoresistance has not yet well established in CRC. In our study, chromatin immunoprecipitation sequencing (ChIP-seq) and Western blot were employed to investigate epigenetic modifications for histones in response to TGF-β1 intervene. We found that the activation of the TGF-β pathway was characterized by genome-wide high levels of H3K9ac and H3K18ac. Mechanistically, the activation of the TGF-β signaling pathway leads to the downregulation of the deacetylase HDAC4, resulting in the upregulation of H3K9ac and H3K18ac. Consequently, this cascade induces oxaliplatin chemoresistance in CRC by triggering the anti-apoptotic PI3K/AKT signaling pathway. Our in vivo experiment results confirmed that overexpression of HDAC4 significantly enhances the sensitivity of CRC to oxaliplatin chemotherapy. Moreover, the expression level of HDAC4 was positively correlated with patients’ prognosis in CRC. Our data suggest that histone-acetyl modification demonstrates a crucial role in modulating TGF-β pathway-associated chemoresistance in CRC, and HDAC4 would be a biomarker for prognostic prediction and potential therapeutic target for treatment in CRC.

This study evaluated the effects of four highland barley proteins (HBPs), namely albumin, globulin, gliadin and glutenin, on the retrogradation and in vitro digestion properties of highland barley starch (HBS). The results showed globulin had the most significant effect on inhibiting short-term retrogradation of HBS, which was reflected in the reduction of G' and G''. Compare with HBS, four HBPs could significantly inhibit long-term recrystallization process. For albumin, globulin, gliadin and glutenin, the degree of retrogradation reduced from 51.55 % to 48.20 %, 35.06 %, 42.22 % and 32.63 %, respectively, which was reflected in the decrease of water migration rate, crystal enthalpy, crystallinity and short-range order. It could be found that glutenin had the most significant effect on inhibiting long-term retrogradation of HBS. Moreover, the anti-digestion properties of retrograded HBS with HBPs intervention significantly increased, with glutenin most significantly. Compared with HBS, resistant starch (RS) content increased by 59.76 % at 28 d of retrogradation.

As the forefront of human–computer intelligent interaction, digital humans have increasingly diverse application scenarios, but also face many challenges. In order to enhance the intelligence level and interaction capability of digital human, the study first optimizes the traditional UniLM model, then introduces the mechanism of multi-head attention, and mitigates the exposure bias by using adversarial training and random replacement of decoder to design an improved UniLM model, and finally applies the improved model to the digital human management system. The results show that the precision rate of the improved UniLM model is improved by 7.68%, 6.4%, and 4.96%, the recall rate is improved by 11.94%, 9.69%, and 8.83%, and the F1-score is improved by 8.34%, 6.41%, and 7.68% compared with the other three models, which proves that it has a better precision rate, robustness, and generalization ability. The perplexity of the improved UniLM model is 135, 95, 76, 71, and 55 under five text lengths, which is significantly lower than the other models, proving that its text generation ability is better. The above results demonstrate the performance of the research-designed digital human system based on the Improved UniLM model, which provides a direction for the further development of digital human technology.

Natural disasters are becoming increasingly regional, frequent, and complex. Semi-quantitative risk assessments based on risk indices or relative risk levels lack quantitative parameters to characterize losses adequately. This study focuses on earthquakes and geological disasters, quantitatively assessing the risk of probable maximum loss (PML) from multi-hazard on the Tibet Plateau (TP) in terms of both absolute and relative values. The results indicate that total PML from multi-hazard on the TP is estimated at 465.5 billion CNY, with a relative value of 5.3%. The total loss value of towns with very high absolute PML is estimated at 254.8 billion CNY, while the relative loss value of towns with very high relative PML is 25.1%. Towns with high absolute value of PML for multi-hazard may have higher fixed asset values, while those with high relative value imply higher vulnerability. Adjusting building structures and reducing the vulnerability of buildings could effectively mitigate the risk of disaster losses caused by multiple hazards.

ABSTRACTThe air quality in China has changed due to the implementation of clean air actions since 2013. Evaluating the spatial pattern of PM2.5 and the effectiveness of reducing anthropogenic emissions in urban and nonurban areas is crucial. Therefore, the China Long-term Air Pollutant dataset for PM2.5 (CLAP_PM2.5) was generated from 2010 to 2022 with a daily 0.1° resolution using the random forest model and integrating multiple data sources, including extensive in-situ PM2.5 measurements, visibility, satellite retrievals, surface and upper-level meteorological data and other ancillary data. The CLAP_PM2.5 dataset is more reliable and accurate than other public datasets. Analysis of CLAP_PM2.5 from 2010 to 2022 reveals the decrease in positive urban-nonurban PM2.5 differences and higher decreasing rates of PM2.5 in most city clusters in eastern China. Furthermore, separating meteorological and emission contributions to the PM2.5 variability by a meteorological normalization approach indicates that meteorological contribution gradually changed from unfavorable to PM2.5 reduction during 2013–2017 to favorable to decline enhancement during 2018–2022, and in urban regions, meteorological contribution is higher than that in nonurban areas. Overall, the reduction in deweathered PM2.5 concentrations highlights China's significant achievements in terms of comprehensive clean air actions.

ABSTRACTFluoroquinolones (FQ) are essential for the treatment of multidrug-resistant tuberculosis (MDR-TB). The FQ resistance (FQ-R) rate in MDR-TB in China and its risk factors remain poorly understood. We conducted a retrospective, population-based genomic epidemiology study of MDR-TB patients in Shanghai, China, from 2009 to 2018. A genomic cluster was defined as strains with genetic distances ≤ 12 single nucleotide polymorphisms. The transmitted FQ-R was defined as the same FQ resistance-conferring mutations shared by ≥ 2 strains in a genomic cluster. We used multivariable logistic regression analysis to identify the risk factors for drug resistance. Among the total 850 MDR-TB patients included in the study, 72.8% (619/850) were male, the median age was 39 (interquartile range 28, 55) years, 52.7% (448/850) were migrants, and 34.5% (293/850) were previously treated patients. Most of the MDR-TB strains belong to the Beijing lineage (91.7%, 779/850). Overall, the genotypic resistance rate of FQ was 34.7% (295/850), and 47.1% (139/295) FQ-R patients were in genomic clusters, of which 98 (33.2%, 98/295) were presumed as transmitted FQ-R. Patients with treatment-naïve (aOR = 1.84; 95% CI: 1.09, 3.16), diagnosed in a district-level hospital (aOR = 2.69; 95% CI: 1.56, 4.75), and streptomycin resistance (aOR = 3.69; 95% CI: 1.65, 9.42) were significantly associated with the transmission of FQ-R. In summary, the prevalence of FQ-R among MDR-TB patients was high in Shanghai, and at least one-third were transmitted. Enforced interventions including surveillance of FQ drug susceptibility testing and screening among MDR-TB before initiation of treatment were urgently needed.