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Finding suitable co-catalysts to help metal sulfides achieve effective bulk phase and surface charge separation is the key to improving their photocatalytic performance. In this paper, two-phase 1T-2H MoSe2 was loaded onto the surface of Mn0.4Cd0.6S solid solution with a twin crystal structure, and the 1T-2H MoSe2/Mn0.4Cd0.6S Z-type heterojunction structure was successfully constructed to realize the high efficiency of hydrogen production in the visible light. The metallic properties of the 1T phase can significantly improve the catalytic activity of MoSe2. The transition from the 2H to the 1T phase can lead to the creation of extra defects, such as unsaturated Mo and Se, thereby increasing the number of active sites on the photocatalyst surface. The two crystalline phases are staggered and form homogeneous junctions within them in the twin crystalline structure Mn0.4Cd0.6S prepared under an alkaline environment, which gives it excellent bulk and charge separation properties. After loading, the 1T phase MoSe2 at the interface of MoSe2 and Mn0.4Cd0.6S can accelerate the charge separation between the interfaces, and the Z-type heterojunctions formed by the two and the better retention of useful excitation electrons and holes. The 1% 1T-2H MoSe2/Mn0.4Cd0.6S could achieve a notable hydrogen production rate of 12.34 mmol ∙ g−1 ∙ h−1, surpassing that of the Mn0.4Cd0.6S solid solution. This non-precious metal-loaded homojunction photocatalyst effectively harnesses solar energy to produce clean H2 under mild conditions, giving a promising prospect for practical applications and laying the groundwork for further exploration of MnxCd1-xS photocatalysts.

Abstract Post-discharge coping difficulty presents a significant challenge for mothers of preterm infants. The readiness for hospital discharge and parenting self-efficacy are crucial factors influencing post-discharge coping difficulty. However, the pathways through which these factors impact post-discharge coping difficulty remain unclear. This study aims to investigate the impact of readiness for hospital discharge on post-discharge coping difficulty and the mediating role of parenting self-efficacy among mothers of preterm infants. A prospective study involving 462 mothers of preterm infants from six tertiary hospitals in Shandong Province was conducted. Mothers were evaluated on the day of discharge (using the Baseline characteristics and Readiness for Hospital Discharge Scale) and three weeks post-discharge (utilizing the Parenting Sense of Competence Scale-Efficacy subscale and Post-Discharge Coping Difficulty Scale). Structural equation modeling was employed to analyze the mediating effect. The results of this study revealed that readiness for hospital discharge significantly decreased post-discharge coping difficulty (β = − 0.533, P

Cutaneous neurofibroma (cNF) is a prevalent clinical manifestation of neurofibromatosis type 1, significantly affecting the well-being and quality of life of the affected individuals. The adoption of reliable and reproducible volumetric measurement techniques is essential for precisely evaluating tumor burden and plays a critical role in the development of effective treatments for cNF. This study focuses on widely used volumetric measurement techniques, including vernier calipers, ultrasound, computed tomography, magnetic resonance imaging, and three-dimensional scanning imaging. It outlines the merits and drawbacks of each technique in assessing the cNF load, providing an overview of their current applications and ongoing research advancements in this domain.

Abstract Understanding the determinants of biodiversity in fragmented habitats is fundamental for informing sustainable landscape development, especially in urban landscapes that substantially fragment natural habitat. However, the relative roles of landscape and habitat characteristics, as emphasized by two competing frameworks (the island biogeography theory and the habitat diversity hypothesis), in structuring species assemblages in fragmented habitats have not been fully explored. This study investigated bird assemblages at 26 habitat patches (ranging in size from 0.3 to 290.4 ha) in an urban landscape, southwest China, among which habitat type composition and woody plant species composition varied significantly. Through 14 bird surveys conducted over six breeding seasons from 2017 to 2022, we recorded 70 breeding bird species (excluding birds recorded only once and fly-overs, such as raptors, swallows and swifts), with an average of 26 ± 10 (SD) species per patch. We found that patch area had significant direct and indirect effects on bird richness, with the indirect effects mediated by habitat richness (i.e., the number of habitat types). Isolation (measured as the distance to the nearest patch), perimeter to area ratio (PAR), and woody plant richness did not significantly predict variation in bird richness. Furthermore, none of these factors significantly sorted bird species based on their functional traits. However, the overall makeup of bird assemblages was significantly associated with the specific habitat types and woody plant species present in the patches. The results suggest that neither the island biogeography theory nor the habitat diversity hypothesis can fully explain the impacts of habitat fragmentation on bird richness in our study system, with their roles primarily being linked to patch area. The findings that habitat and plant compositions were the major drivers of variation in bird assemblage composition offer valuable insights into urban planning and green initiatives. Conservation efforts should focus not only on preserving large areas, but also on preventing urban monocultures by promoting diverse habitats within those areas, contributing to the persistence of meta-communities.

Abstract Background Colorectal cancer (CRC) poses a significant public health challenge in Canada, with the Atlantic provinces bearing a particularly high burden. The implementation of population-based colon screening programs is aimed to address this concern. However, limited research exists on the effect of these programs especially in Canada. This study aimed to examine the impact of the first few years of the CRC screening programs in the Atlantic provinces of Canada by assessing changes in screening uptake, barriers, and predictors of screening among eligible populations. Methods Employing a repeated cross-sectional design, this study analyzed data from a representative sample of 7614 respondents in 2010 and 6850 in 2017 from the Atlantic provinces aged 50–74 years, extracted from the Canadian Community Health Survey (CCHS). The outcomes measured were CRC screening rates, changes in predictors of screening uptake, and barriers to participation. Potential predictors examined included age, sex, income, education, smoking, and health status. Results The proportion of adults aged 50–74 years who meet CRC screening requirements increased from 42% in 2010 to 54% in 2017 yet below the national target of 60%. New Brunswick reported the most significant increase in screening prevalence (18%, p 60 years, OR = 2.09, p

Merging bound states in the continuum (BICs) and avoided crossing of resonances (ACR) are promising theoretical approaches to greatly enhance the quality (Q) factors of quasi-BICs in reciprocal space. We observe the phenomena of merging BICs and ACR in millimeter-sized C4v symmetry photonic crystal structures. The ACR at Γ point is obtained in the variation of the structural parameter. In off-Γ region, the merging BICs at arbitrary locations are observed in the experimental measurements. The findings offer a pathway to high-performance photonic devices with potential applications in optoelectronics and microwave experimentation.

Objective The guidelines recommend early caffeine administration for preterm infants requiring non-invasive mechanical ventilation since earlier treatment is associated with better outcomes. The objective was to evaluate the impact of early caffeine therapy (within 24 hours after birth) on respiratory outcomes in very preterm infants who were initially receiving invasive mechanical ventilation.Methods This was an observation cohort study from 1 January 2018 to 31 December 2022 based on a database that was prospectively collected and maintained. Infants who initially received invasive mechanical ventilation were divided into two groups based on the timing of caffeine initiation: within the first 24 hours after birth (early) and within 48 hours of birth or later (late). Generalised linear mixed models with a random effect model for the centre were used to assess the impact of different caffeine initiation times on neonatal outcomes.Results Among the cohort of 9880 infants born at

BackgroundRapidly developed chemoresistance to dacarbazine (DTIC) is a major obstacle in the clinical management of melanoma; however, the roles and mechanisms of epi-transcriptomic RNA modification in this process have not been investigated.MethodDTIC-resistant (DR) melanoma cells were established for bulk RNA sequencing. The expressions of mRNAs were detected using qRT-PCR, and protein levels were determined using Western blotting and immunohistochemistry. Acetylated RNAs were detected by dot blotting and immunoprecipitation sequencing (acRIP-seq). A lung metastasis mouse model of melanoma was established to evaluate the anti-melanoma effects in vivo.ResultsWe identified that the expression of N-acetyltransferase 10 (NAT10), a catalytic enzyme for the N4-acetylcytidine (ac4C) modification of RNA, was significantly upregulated in the DR cells. Clinically, NAT10 expression was elevated in disease progression samples and predicted a poor outcome. Using ac4C RNA immunoprecipitation (ac4C-RIP), we found that the mRNAs of two C2H2 zinc finger transcriptional factors, DDX41 and ZNF746, were targets of NAT10-mediated ac4C modification. Gain- and loss-of-function experiments in NAT10, or in DDX41 and ZNF746, altered the chemosensitivity of melanoma accordingly, and the two target genes also negatively correlated with clinical outcomes. Finally, pharmacological inhibition of NAT10 with Remodelin sensitized melanoma cells to DTIC treatment in vitro and in a mouse xenograft model.ConclusionOur study elucidates the previously unrecognized role of NAT10-mediated ac4C modification in the chemoresistance of melanoma and provides a rationale for developing new strategies to overcome chemoresistance in melanoma patients.

Abstract A global outbreak of monkeypox (mpox) caused by the mpox virus (MPXV) has posed a serious threat to public health worldwide, thus calling for the urgent development of antivirals and vaccines to curb its further spread. In this study, we screened 41 anhydride‐modified proteins and found that 3‐hydroxyphthalic anhydride‐modified β‐lactoglobulin (3HP‐β‐LG), a clinically used anti‐HPV agent, was highly effective in inhibiting infection of vaccinia virus Tiantan strain (VACV‐VTT) and MPXV. Mechanistic studies demonstrated that 3HP‐β‐LG bound to the virus, not the host cell, by targeting the early stage of virus entry, possibly through the interaction between the amino acids with negatively charges in 3HP‐β‐LG and the key amino acids with positive charges in the target region of A29L, a key surface protein of MPXV. A synergistic effect was observed when 3HP‐β‐LG was combined with tecovirimat, a small‐molecule antiviral drug approved by the United States Food and Drug Administration and the European Medicine Agency for the treatment of smallpox and mpox. Because of its clinically proven safety and stability, 3HP‐β‐LG shows promise for further development as a prophylactic agent to prevent the sexual transmission of MPXV.

ObjectivesTo explore the impact of lymph node diameter on the efficacy and safety of ultrasound-guided microwave ablation (MWA) in the treatment of cervical metastatic lymph nodes (CMLNs) from thyroid cancer.MethodsA total of 32 patients with 58 CMLNs from thyroid cancer underwent ultrasound-guided MWA and were included in the retrospective study. Patients were divided into three groups based on the mean largest diameter of the CMLNs: Group A (diameter ≤10mm), Group B (10mm < diameter ≤20mm), and Group C (diameter >20mm). The research involved comparing changes in cervical metastatic lymph nodes and serum thyroglobulin (sTg) levels, as well as the incidence of complications, before and after microwave ablation across three groups of patients.ResultsThe technical success rate of this study was 100% (32/32), and they showed no major complications. Compared with measurements taken before MWA, the mean largest diameter and volume of CMLNs, as well as the sTg level, showed significant reductions (p Group B > Group A. The occurrence rate of mild complications was Group A > Group C > Group B.ConclusionMWA is a safe and effective method for treating CMLNs, with advantages for localized nodes but limitations for larger ones. Careful consideration and personalized plans are advised, based on comprehensive evidence assessment.

This case report aims to highlight the importance of considering lymphoma as a potential differential diagnosis in patients presenting with laryngeal mass and associated cervical lymphadenopathy, particularly those with a history of chronic tonsillitis. A case of a 63-year-old male patient who underwent bilateral tonsillectomy for tumor in the left tonsil was presented. Two months after the procedure, he developed throat discomfort, dysphagia, neck swelling, and other symptoms. The patient was initially diagnosed with “tongue base mass” and chronic lymphadenitis. Partial excision of the tongue base mass was performed twice in another hospital, revealing chronic inflammation of the epithelial mucosa. Further evaluations, including electron laryngoscopy and imaging studies, were conducted to investigate the condition. A computed tomography (CT) scan showed irregular soft tissue density in the oropharyngeal region, along with multiple lymph nodes in the neck. Subsequent histopathological examination of the lingual base biopsy revealed peripheral T-cell lymphoma with a follicular T-helper cell phenotype. Immunohistochemical staining confirmed specific markers while ruling out other markers. In situ hybridization testing demonstrated positivity for Epstein–Barr virus-encoded RNA, and TCRG clonality was confirmed. The duration from symptom onset to diagnosis was 2 months. This case emphasizes the importance of considering lymphoma in patients with laryngeal mass and associated cervical lymphadenopathy, especially when a history of chronic tonsillitis is present. Accurate diagnosis and early intervention are crucial for effective management and improved patient outcomes.

The ambient air quality standard (AAQS) is a vital policy instrument for protecting the environment and human health. Hainan Province is at the forefront of China's efforts to protect its ecological environment, with an official goal to achieve world-leading air quality by 2035. However, neither the national AAQS nor the World Health Organization guideline offers sufficient guidance for improving air quality in Hainan because Hainan has well met the former while the latter is excessively stringent. Consequently, the establishment of Hainan's local AAQS becomes imperative. Nonetheless, research regarding the development of local AAQS is scarce, especially in comparatively more polluted countries such as China. The relatively high background values and significant interannual fluctuations in air pollutant concentrations in Hainan present challenges in the development of local AAQS. Our research proposes a world-class local AAQS of Hainan Province by reviewing the AAQS in major countries or regions worldwide, analyzing the influence of different statistical forms, and carefully evaluating the attainability of the standard. In the proposed AAQS, the annual mean concentration limit for PM2.5, the annual 95th percentile of daily maximum 8-h mean (MDA8) concentration limit for O3, and the peak season concentration limit for O3 are set at 10, 120, and 85 μg/m3, respectively. Our study indicates that, with effective control policies, Hainan is projected to achieve compliance with the new standard by 2035. The implementation of the local AAQS is estimated to avoid 1,526 (1,253–1,789) and 259 (132–501) premature deaths attributable to long-term exposure to PM2.5 and O3 in Hainan in 2035, respectively.

Abstract To solve three-dimensional structures of biological macromolecules in situ, large numbers of particles often need to be picked from cryo-electron tomograms. However, adoption of automated particle-picking methods remains limited because of their technical limitations. To overcome the limitations, we develop DeepETPicker, a deep learning model for fast and accurate picking of particles from cryo-electron tomograms. Training of DeepETPicker requires only weak supervision with low numbers of simplified labels, reducing the burden of manual annotation. The simplified labels combined with the customized and lightweight model architecture of DeepETPicker and accelerated pooling enable substantial performance improvement. When tested on simulated and real tomograms, DeepETPicker outperforms the competing state-of-the-art methods by achieving the highest overall accuracy and speed, which translate into higher authenticity and coordinates accuracy of picked particles and higher resolutions of final reconstruction maps. DeepETPicker is provided in open source with a user-friendly interface to support cryo-electron tomography in situ.

Abstract Background Artificial intelligence (AI)-assisted clinical trial screening is a promising prospect, although previous matching systems were developed in English, and relevant studies have only been conducted in Western countries. Therefore, we evaluated an AI-based clinical trial matching system (CTMS) that extracts medical data from the electronic health record system and matches them to clinical trials automatically. Methods This study included 1,053 consecutive inpatients primarily diagnosed with hepatocellular carcinoma who were referred to the liver tumor center of an academic medical center in China between January and December 2019. The eligibility criteria extracted from two clinical trials, patient attributes, and gold standard were decided manually. We evaluated the performance of the CTMS against the established gold standard by measuring the accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and run time required. Results The manual reviewers demonstrated acceptable interrater reliability (Cohen’s kappa 0.65–0.88). The performance results for the CTMS were as follows: accuracy, 92.9–98.0%; sensitivity, 51.9–83.5%; specificity, 99.0–99.1%; PPV, 75.7–85.1%; and NPV, 97.4–98.9%. The time required for eligibility determination by the CTMS and manual reviewers was 2 and 150 h, respectively. Conclusions We found that the CTMS is particularly reliable in excluding ineligible patients in a significantly reduced amount of time. The CTMS excluded ineligible patients for clinical trials with good performance, reducing 98.7% of the work time. Thus, such AI-based systems with natural language processing and machine learning have potential utility in Chinese clinical trials.

Background: Type 1 diabetes mellitus (T1DM) may be associated with various autoimmune diseases, but the causal relationship between T1DM and autoimmune skin diseases is not yet clear. Methods: The summary statistical data on T1DM and nine autoimmune skin diseases in European populations were extracted for mendelian randomization (MR) analysis. Subsequently, the analysis was replicated in East Asian populations. In the MR estimation, inverse variance-weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode methods were utilized. Outliers were excluded using MR-PRESSO, and horizontal pleiotropy was assessed with MR-Egger. Additionally, a multivariable MR analysis was conducted to investigate whether T1DM has an independent effect on autoimmune skin diseases after adjusting for potential confounders. Results: In Europe, the MR estimated based on IVW method indicated a causal association between genetically determined T1DM and systemic lupus erythematosus (SLE) (OR = 1.38, 95%CI: 1.26−1.50, p＜0.01), rheumatoid arthritis (RA) (OR = 1.15, 95%CI: 1.05−1.25, p＜0.01), as well as multiple sclerosis (MS) (OR = 1.17, 95%CI: 1.01−1.36, p = 0.04), but there is no association between T1DM and atopic dermatitis (AD), vitiligo, lichen planus (LP), hidradenitis suppurativa (HS), alopecia areata (AA) and systemic sclerosis (SS). After adjusting for time spent watching television, body mass index, type 2 diabetes mellitus, and body fat percentage, we found a causal relationship between T1DM and SLE (OR = 1.29, 95%CI: 1.16–1.44, p

Hyalinizing clear cell carcinomas (HCCCs) are infrequent, malignant tumors characterized by their low-grade nature. They typically originate from minor salivary glands. However, these tumors can potentially emerge in any location with minor salivary glands, including the nasopharynx. This report presents two cases of HCCC in females aged 61 and 72 years, with both tumors approximately 4 cm in size. In the first case, a 72-year-old female presented with recurrent bilateral epistaxis. Imaging studies revealed a nasopharyngeal mass, surgically excised, and histopathological analysis confirmed HCCC. Postoperatively, the patient received combined chemotherapy and radiotherapy, achieving a recurrence-free status 2.5 years later. The second case involves a 61-year-old female with a two-year history of bloody nasal discharge. Imaging studies identified a nasopharyngeal lesion, surgically removed, and histopathological examination confirmed HCCC. This patient underwent radiotherapy followed by combination chemotherapy with paclitaxel and carboplatin, displaying no signs of recurrence upon reevaluation after 10 months. These cases highlight the successful management of HCCC through a comprehensive, multimodal approach, integrating surgical intervention and adjuvant therapy. The favorable outcomes emphasize the significance of a thorough treatment strategy for HCCC in the nasopharynx, providing valuable insights for clinicians. Further studies are essential to enhance our understanding of this rare entity and refine treatment protocols for optimized patient outcomes.

Abstract Examining beta diversity of animal assemblages in fragmented habitats, which measures variation in species composition among different fragments, is important for understanding the impact of habitat fragmentation on biodiversity. However, relying solely on taxonomic composition may not provide a comprehensive understanding. Incorporating measures of functional and phylogenetic diversities is essential for elucidating the ecological mechanisms underlying changes in community composition. In addition, prevailing studies often prioritize the evaluation of landscape characteristics within fragments as determinants of beta diversity, neglecting differences in habitat type and plant community composition. In this study, we surveyed birds in 26 remnant woodlot patches (ranging from 0.3 to 290.4 ha) in an urban landscape, southwest China, during the breeding season from 2017 to 2022. We recorded 70 bird species (excluding those recorded only once and high‐flying birds, including raptors, swallows, and swifts), with the number of species per patch varying from 14 to 56. The overall bird taxonomic and phylogenetic beta diversities were primarily contributed by the turnover component, while functional beta diversity was dominated by the nestedness‐resultant component. Patch area and perimeter area ratio significantly influenced the taxonomic, functional, and phylogenetic beta diversities, primarily mediated through the nestedness‐resultant component, while inter‐patch distance had a significant effect via the turnover component. In addition, there was a considerable correlation of bird taxonomic, functional, and phylogenetic beta diversities with habitat type and woody plant beta diversities, including their respective partitioned turnover and nestedness‐resultant components. Our results suggest that bird assemblages in these patches may be regulated by selective extinction, interspecific competition, and environmental filtering. The findings have significant implications for sustainable landscape planning and habitat restoration. Conserving habitat patches of different sizes and maintaining or enhancing habitat heterogeneity between patches can facilitate the persistence of metacommunities.

Proper nutrient management is crucially important to the sustainable development of tea production. Compared to normal green-leaf cultivars, albino tea cultivars produce green tea of superior quality characterized by high contents of amino acids as a result of the hydrolysis of chloroplast proteins at albinism. However, the advantage of albino tea cultivars was offset by inferior growth and yield performance because of low contents of chlorophylls and limited photosynthesis capacity. Our understanding about the nutrition characteristics of albino tea cultivars was very limited. A four-year field experiment was conducted to develop proper nutrient management for Baiye-1 to overcome its weakness of low productivity without a tradeoff in tea quality and environmental risks. The nutrient management schemes were formulated by optimizing the rate and ratio of nitrogen (N), phosphorus, potassium and magnesium together with substitution of chemical fertilizers with organic manures. The total amounts of nutrients in the optimized schemes were reduced by 25% compared to the local farmers’ practice (FP). Results showed that optimized rates and ratio of nutrients together with partial substitution of chemical fertilizers with rapeseed cake manure more considerably improved albino tea yield, the contents of free amino acids, total polyphenol and catechins relative to FP. Partial substitution of chemical fertilizers with commercial livestock manure decreased tea quality, which was likely caused by a dilution effect of increasing tea yield and decreasing N status of tea plants. Full organic substitution of chemical fertilizers by rapeseed cake manure improved tea yield and quality but had relatively low agronomic efficiency and profit. The effect of optimized nutrient management schemes was associated with the improvement of nutritional status in tea plants. The present work demonstrated that the optimization of nutrient management considerably improved albino tea yield, quality and profit while decreased the application rate of fertilizers and the intensity of greenhouse gas emissions.

Abstract The reductions in aerosols often exacerbate climate warming. It remains unclear how to effectively alleviate PM2.5 pollution while minimizing the penalty on climate warming. Here we identify the clean air measures in China that are associated with low aerosol climate penalty efficiency (ACPE), which is defined as aerosol radiative forcing per unit PM2.5 concentration reduction. The measures in transportation, residential combustion, and open burning sectors generally caused lower ACPE [0.07, 0.24, and 0.10 (W m−2)/(μg m−3)] than those from other sectors [0.34–0.46 (W m−2)/(μg m−3)]. This is ascribed to relatively small decreases in cloud concentration nuclei per unit PM2.5 reduction in these sectors, which is further attributed to either relatively low aerosol hygroscopicity or relatively small decrease in aerosol number. Most measures in the former three sectors have low ACPE of

Human adenovirus type 7 (HAdV-7) is a significant viral pathogen that causes respiratory infections in children. Currently, there are no specific antiviral drugs or vaccines for children targeting HAdV-7, and the mechanisms of its pathogenesis remain unclear. The NLRP3 inflammasome-driven inflammatory cascade plays a crucial role in the host’s antiviral immunity. Our previous study demonstrated that HAdV-7 infection activates the NLRP3 inflammasome. Building upon this finding, our current study has identified the L4 100 kDa protein encoded by HAdV-7 as the primary viral component responsible for NLRP3 inflammasome activation. By utilizing techniques such as co-immunoprecipitation, we have confirmed that the 100 kDa protein interacts with the NLRP3 protein and facilitates the assembly of the NLRP3 inflammasome by binding specifically to the NACHT and LRR domains of NLRP3. These insights offer a deeper understanding of HAdV-7 pathogenesis and contribute to the development of novel antiviral therapies.

Objectives The objective was to investigate the associations of maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) trajectories with adverse pregnancy outcomes (APOs).Design This was a prospective cohort study.Setting This study was conducted in Shanghai Pudong New Area Health Care Hospital for Women and Children, Shanghai, China.Primary and secondary outcome measures A cohort study involving a total of 2174 pregnant women was conducted. Each participant was followed to record weekly weight gain and pregnancy outcomes. The Institute of Medicine classification was used to categorise prepregnancy BMI, and four GWG trajectories were identified using a latent class growth model.Results The adjusted ORs for the risks of large for gestational age (LGA), macrosomia, gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP) were significantly greater for women with prepregnancy overweight/obesity (OR=1.77, 2.13, 1.95 and 4.24; 95% CI 1.3 to 2.42, 1.32 to 3.46, 1.43 to 2.66 and 2.01 to 8.93, respectively) and lower for those who were underweight than for those with normal weight (excluding HDP) (OR=0.35, 0.27 and 0.59; 95% CI 0.22 to 0.53, 0.11 to 0.66 and 0.36 to 0.89, respectively). The risk of small for gestational age (SGA) and low birth weight (LBW) was significantly increased in the underweight group (OR=3.11, 2.20; 95% CI 1.63 to 5.92, 1.10 to 4.41; respectively) compared with the normal-weight group; however, the risk did not decrease in the overweight/obese group (p=0.942, 0.697, respectively). GWG was divided into four trajectories, accounting for 16.6%, 41.4%, 31.7% and 10.3% of the participants, respectively. After adjustment for confounding factors, the risk of LGA was 1.54 times greater for women in the slow GWG trajectory group than for those in the extremely slow GWG trajectory group (95% CI 1.07 to 2.21); the risk of SGA and LBW was 0.37 times and 0.46 times lower for women in the moderate GWG trajectory group and 0.14 times and 0.15 times lower for women in the rapid GWG trajectory group, respectively; the risk of macrosomia and LGA was 2.65 times and 2.70 times greater for women in the moderate GWG trajectory group and 3.53 times and 4.36 times greater for women in the rapid GWG trajectory group, respectively; and the women in the other three trajectory groups had a lower risk of GDM than did those in the extremely slow GWG trajectory group, but there was not much variation in the ORs. Notably, different GWG trajectories did not affect the risk of HDP.Conclusions As independent risk factors, excessively high and low prepregnancy BMI and GWG can increase the risk of APOs.

Background: The relationship between fruit, whole grain, and total energy consumption and the gut microbiome in the Chinese population remains unclear. Objective: We investigated the relationship between intakes of fruits, whole grains, and energy, and the diversity and composition of gut microbiota. Design: This cross-sectional study included 167 subjects aged 40-75 years who underwent colonoscopy at Nankai Hospital in Tianjin, China. Each of the participants completed a personal history questionnaire, a 7-day dietary record, and donated a fecal sample. The V3-V4 hypervariable region of the bacterial 16S rRNAgene was amplified and sequenced using Illumina Novaseq. The relationship between diet and gut microbiota was evaluated in terms of both the overall composition and the abundance of specific taxon. Results: Fruits intake was positively related to the abundance of Bacilli, Porphyromonadaceae, Streptococcaceae, Parabacteroides, Streptococcus, and Bilophila in fecal samples. Higher whole grains intake was associated with higher microbial diversity, as measured by Shannon, Simpson, and Chao1 indices. Specifically, there was a significant increase inthe relative abundance of Lachnospiraceae and a decrease in Actinobacteria with increased whole grains intake. Moreover, higher intake of total energy was associated with a lower abundance of Anaerostipes and a higher abundance of Lactobacillales and Acidaminococcus. Conclusion: Whole grains intake was positively associated with gut microbial diversity. Fruits and total energy intake were related to the abundance of specifictaxon (e.g., Bacilli and Acidaminococcus). These findings highlight the potential importance of dietary interventions for modulating gut microbiota composition and promoting overall health.

In order to improve the production efficiency of the coal washing process, increase the service life of the washing equipment, maximize the potential production capacity of the screening equipment in the coal preparation plant, improve the rationality of the screening process, comprehensively improve the relaxation screen screening system and reduce the wear rate of the screen surface due to the high screening efficiency, a measure of adjusting the performance parameters of the relaxation screen is proposed to optimize the screening efficiency and reduce the wear of the screen surface. The flexible sieve plate is discretized to reduce the complexity of the simulation process of the flexible sieve plate, and the multi-body dynamics simulation and the discrete element method are used to numerically simulate the sieving process of the sieve surface, and the performance parameters of the relaxation sieve are obtained. : The influence law of relaxation frequency, sieve surface inclination, and relaxation amount on screening efficiency, and considering the correlation coefficient method and the significance test method comprehensively, it is determined that the relaxation amount is a non-key factor affecting the screening efficiency. On the basis of summarizing the wear law of the relaxation sieve screening process, the influence law of the sieve surface relaxation amount on the wear depth in the simulation process is obtained through the Relative Wear and Archard Wear models. Based on the dual effects of relaxation on screening efficiency and wear depth, the linear weighting method was selected for multi-objective optimization of screen surface performance, and the performance parameters of the screen surface that ensured the highest screening efficiency and minimum wear depth were obtained and verified by simulation. The research results show that: the screening efficiency decreases with the increase of the inclination angle of the screen surface, and the greater the relaxation amount and the relaxation frequency, the change rule increases first and then decreases; After increasing, the trend decreases. Considering the screening efficiency and the wear of the screen surface comprehensively, the optimal performance parameters of the screen surface are obtained, that is, when the relaxation amount of the screen surface is selected as 5 mm, the screening efficiency can reach 80.85%, and the wear depth of the screen surface It is only 0.051 6 mm, compared with the optimal screening efficiency, the wear of the screen surface is reduced by 26.5%, while the screening efficiency is only reduced by 0.48%, which can significantly reduce the wear of the screen surface under the condition that the screening efficiency is less affected. It shows that the sieving performance of the optimized relaxation sieve has been significantly improved. The adoption of the above technical solutions can effectively improve the performance parameters of the screening link in the washing process, improve the production capacity of the equipment, and provide technical support for the intelligence of the washing system of the coal preparation plant.

Abstract The propulsion for mammalian sperm swimming is generated by flagella beating. Microtubule doublets (DMTs) along with microtubule inner proteins (MIPs) are essential structural blocks of flagella. However, the intricate molecular architecture of intact sperm DMT remains elusive. Here, by in situ cryo-electron tomography, we solved the in-cell structure of mouse sperm DMT at 4.5–7.5 Å resolutions, and built its model with 36 kinds of MIPs in 48 nm periodicity. We identified multiple copies of Tektin5 that reinforce Tektin bundle, and multiple MIPs with different periodicities that anchor the Tektin bundle to tubulin wall. This architecture contributes to a superior stability of A-tubule than B-tubule of DMT, which was revealed by structural comparison of DMTs from the intact and deformed axonemes. Our work provides an overall molecular picture of intact sperm DMT in 48 nm periodicity that is essential to understand the molecular mechanism of sperm motility as well as the related ciliopathies.

Abstract The common human coronaviruses (HCoVs) HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1 which are members of the coronavirus family are long co-existed with humans and widely distributed globally. Common HCoVs usually cause mild, self-limited upper respiratory tract infections (URTI), and also associated with lower respiratory tract infections (LRTI), especially in children. However, there are little multicentre studies have been conducted in children of several different areas in China, and the epidemic potential of common HCoVs remains unclear. Understanding of the common HCoVs is valuable for clinical and public health. Herein, we retrospectively analysed the medical records of children with acute lower respiratory tract infection admitted to 9 hospitals from different regions in China from 2014 to 2019. Of the 124 patients who tested positive for coronaviruses, OC43 was the predominant type, accounting for 36.3% (45/124) of the detections. Children aged ≤ 6 months and 12–23 months had the highest detection rate of common HCoVs, and the detection rate gradually declined after 2 years old. These four HCoVs could be detected all year round. Among the areas of our study, the overall positive rate was higher in southern China, especially in Guangzhou (29/124, 23.4%). Moreover, common HCoV-positive patients were codetected with 9 other common respiratory pathogens. 229E (11/13, 84.6%) was the most frequently associated with codetection, with EV/RhV was the most frequently codetected virus. Cough (113/124, 91.1%) and fever (73/124, 58.9%) were the most common symptoms of common HCoVs infection.

AIM: To investigate time trends in myopia and high myopia prevalence over 6y among young university adults in China. METHODS: This is a 6-year series cross-sectional study from 2016 to 2021. Totally 4910 freshmen were enrolled and completed a questionnaire concerning age, gender, and disease history. Students with eye diseases were excluded after a detailed eye examination. The refractive status was measured by non-cycloplegic objective refraction and ocular parameters were measured by Lenstar 900. The examination followed the same protocol each year. Trends over time in myopia and high myopia prevalence, as well as ocular biometry parameters, were analyzed. RESULTS: From 2016 to 2021, the axial length (AL) and corneal radius (CR) increased significantly (P=0.002 for AL; P=0.04 for CR). However, the spherical equivalent (SE) and the ratio of axial length to the corneal radius (AL/CR) did not change significantly (P=0.59 for SE; P=0.24 for AL/CR). The frequency of AL ≥26.0 mm increased from 26.6% in 2016 to 29.3% in 2021 (P=0.05 for trend). The prevalence of myopia and high myopia did not change significantly in our study (P≥0.18). Compared to a similar cross-sectional study conducted 10 years ago, the prevalence of myopia decreased significantly (94.9% vs 91.8%, P

Abstract For tumor treatment, the ultimate goal in tumor therapy is to eliminate the primary tumor, manage potential metastases, and trigger an antitumor immune response, resulting in the complete clearance of all malignant cells. Tumor microenvironment (TME) refers to the local biological environment of solid tumors and has increasingly become an attractive target for cancer therapy. Neutrophils within TME of gastric cancer (GC) spontaneously undergo ferroptosis, and this process releases oxidized lipids that limit T cell activity. Enhanced photodynamic therapy (PDT) mediated by di‐iodinated IR780 (Icy7) significantly increases the production of reactive oxygen species (ROS). Meanwhile, neutrophil ferroptosis can be triggered by increased ROS generation in the TME. In this study, a liposome encapsulating both ferroptosis inhibitor Liproxstatin‐1 and modified photosensitizer Icy7, denoted LLI, significantly inhibits tumor growth of GC. LLI internalizes into MFC cells to generate ROS causing immunogenic cell death (ICD). Simultaneously, liposome‐deliver Liproxstatin‐1 effectively inhibits the ferroptosis of tumor neutrophils. LLI‐based immunogenic PDT and neutrophil‐targeting immunotherapy synergistically boost the anti‐PD‐1 treatment to elicit potent TME and systemic antitumor immune response with abscopal effects. In conclusion, LLI holds great potential for GC immunotherapy.

Metabolic syndrome is associated with cardiovascular dysfunction, including elevated sympathetic outflow. However, the underlying brain mechanisms are unclear. The nucleus tractus solitarius (NTS) critically regulates autonomic reflexes related to cardiovascular function and contains neurons projecting to the caudal ventrolateral medulla (CVLM). Nitric oxide (NO) is a diffusible free-radical messenger in the vascular, immune, and nervous systems. In this study, we determine if NO in the NTS is involved in the synaptic plasticity underlying the elevated sympathetic outflow in fructose-induced hypertension. We retrogradely labeled CVLM-projecting NTS neurons through the injection of FluoSpheres into the CVLM in a fructose-fed rat model to determine the cellular mechanism involved in increased sympathetic outflow. Fructose feeding increased the blood pressure and glucose levels, which represent metabolic syndrome. We found that fructose feeding reduces the NO precursor L-arginine-induced increase in the firing activity of CVLM-projecting NTS neurons. Furthermore, fructose feeding reduces the L-arginine-induced increase in presynaptic spontaneous glutamatergic synaptic inputs to NTS neurons, while NO donor DEA/NO produces an increase in glutamatergic synaptic inputs in fructose-fed rats similar to that in vehicle-treated rats. In addition, fructose feeding reduces the NO-induced depressor response and sympathoinhibition. These data suggested that fructose feeding reduced NO production and, thus, the subsequent NO-induced glutamate releases in the NTS and depressor response. The findings of this study provide new insights into the central mechanisms involved in the neural control of cardiovascular and autonomic functions in the NTS in metabolic syndrome.

To address the problems of current mainstream semantic segmentation network such as rough edge segmentation of navel oranges defects, poor accuracy of small target defect segmentation and insufficient deep-level semantic extraction of defects, feature information will be lost, a multi-class segmentation model based on improved DeepLabv3+ is proposed to detect the surface defects of navel oranges. The Coordinate Attention Mechanism is embedded into the DeepLabv3+ network for better semantic segmentation performance, while the dilated convolution of Atrous Spatial Pyramid Pooling structure is replaced with deformable empty convolution to improve the fitting ability of the network to target shape changes and irregular defects. In addition, a BiFPN-based feature fusion branch is introduced at the DeepLabv3+ encoder side to realize multi-scale feature fusion and enrich feature space and semantic information. The experimental results show that the average intersection ratio and average pixel intersection ratio accuracies of the improved DeepLabv3+ model on the navel orange surface defect dataset are 77.32% and 86.38%, which are 3.81% and 5.29% higher than the original DeepLabv3+ network, respectively, improving the extraction capability of navel orange defect features and having better segmentation performance.

The highly conserved hydrophobic pocket region of HIV-1 gp41 NHR triple-stranded coiled coil is crucial for the binding of CHR to NHR to form a six-helix bundle (6-HB). This pocket is only exposed instantaneously during fusion, making it an ideal target for antibody drug design. However, IgG molecule is too big to enter the pocket during the fusion process. Therefore, to overcome the steric hindrance and kinetic obstacles caused by the formation of gp41 pre-hairpin fusion intermediate, we obtained nanobodies (Nbs) targeting NHR by immunizing alpaca with an NHR-trimer mimic. Specifically, we identified a Nb, Nb-172, that exhibited potent and broadly neutralizing activity against HIV-1 pseudoviruses, HIV-1 primary isolates, and T20-resistant HIV-1 strains. In addition, the combinatorial use of mD1.22 and Nb-172 exhibited synergism in inhibiting HIV-1 infection inactivating cell-free virions. Nb-172 can competitively bind to the hydrophobic pocket of gp41 NHR to inhibit 6-HB formation. These findings suggest that Nb-172 merits further investigation as a potential therapeutic for HIV-1 infection.

Abstract BRD4 is a member of the BET protein family involved in chromatin remodeling and transcriptional regulation. Several BET inhibitors (BETi) have entered clinical trials, demonstrating potential in inducing cancer cell apoptosis and tumor regression. However, resistance to BETi is common in solid tumors. In pancreatic cancer, it is found that cancer‐associated fibroblasts (CAFs) in the tumor microenvironment reduce the BET inhibitor JQ1 sensitivity by inducing BRD4 expression. Moreover, CAFs play a crucial role in the formation of a dense stromal barrier. Therefore, targeting CAFs in the tumor microenvironment of pancreatic cancer not only enhances cancer cells sensitivity to JQ1 but also increases drug perfusion and improves oxygen supply, thus reducing glycolysis and limiting energy supply. To address this challenge, a homologous targeting mechanism utilizing activated fibroblast membrane‐coated liposomes is proposed for specific drug precise target to CAFs‐rich pancreatic cancer. Additionally, TAT peptides enable liposomes penetration, delivering PFD for targeted anti‐fibrotic therapy, reducing extracellular matrix generation and glycolysis, and enhancing JQ1 delivery and sensitivity. In conclusion, the findings indicate the tremendous potential of this CAFs‐targeting liposomal delivery system in pancreatic cancer.

Background and objectivesThe potential association between rosacea and a heightened prevalence of Helicobacter pylori (HP) infection has been previously suggested. However, existing studies offer inconsistent results. This systematic review and meta-analysis aimed to elucidate the relationship between rosacea and HP infection.MethodsWe conducted comprehensive searches of PubMed, Embase, and Web of Science databases to identify relevant observational studies for our investigation. We utilized the random-effects model to aggregate the data to address the potential influence of heterogeneity among the studies on the outcome.ResultsOur analysis incorporated twenty-five datasets from 23 case-control and cross-sectional studies, encompassing 51,054 rosacea patients and 4,709,074 controls without skin disease. The pooled results revealed a significantly higher prevalence of HP infection in individuals with rosacea compared to controls (odds ratio [OR]: 1.51, 95% confidence interval [CI]: 1.17-1.95, pConclusionRosacea may be significantly associated with a higher prevalence of HP infection. High-quality prospective studies with delicately controlled confounding factors are needed to determine if HP infection is a risk factor for rosacea.

The automatic cutting of coal and rock surface morphology modeling based on the actual geological environment of coal mine underground excavation and mining is of great significance for improving the surface quality of coal and rock after cutting and enhancing the safety and stability of advanced support. To this end, using the principle of coordinate transformation, the kinematic trajectory of the cutting head of the tunneling machine is established, and the contour morphology of the cutting head under variable cutting technology is obtained. Then, based on the regenerative vibration theory of the cutting head, a dynamic model of the cutting head coal wall is established, and the coordinate relationship of the cutting head in the tunnel coordinate system under vibration induction is analyzed. Based on fractal theory and Z-MAP method, a simulation method for the surface morphology of coal and rock after cutting is proposed, which is driven by the cutting trajectory Under the coupling effect of cutting vibration induction and random fragmentation of coal and rock, simulation of the surface morphology of comprehensive excavation tunnels was conducted, and relevant experiments were conducted to verify the results. A 1:3 similarity experimental model of EBZ160 tunneling machine was used to build a cutting head coal and rock system cutting experimental platform for comparative experiments of cutting morphology. Furthermore, statistical methods were used to compare and evaluate the simulated roof with the actual roof. The results show that the relative errors between the maximum range of peaks and valleys, the peak skewness coefficient of height standard deviation, and the kurtosis coefficient of the actual roof are 1.3%, 24.5%, 16%, and 2.9%, respectively. Overall, this indicates that the surface morphology distribution characteristics of the simulated roof and the actual roof are similar, verifying the effectiveness of the modeling and simulation method proposed in this paper, and providing theoretical support for the design and optimization of advanced support in the future.

Using three musical pieces as musical stimuli from Romania, Brazil, and Saudi Arabia, this study extended Fung’s study by examining Chinese pre-service music teachers’ (n = 115) and schoolteachers’ (n = 131) personal preferences and external preferences for orchestral, folk, and popular music pieces. Two groups of participants were asked to select their preferred music from three pieces and to provide verbal descriptions of the reasons for their selections. The results showed (a) no significant differences in personal preference between the two groups but statistical significances in external preferences between the two groups; (b) the highest preference rating by both groups of teachers was folk music and the highest forced-choice preference was popular music; (c) statistically significant correlations between personal preference and external preference were evident in both groups across all three pieces; and (d) frequent descriptions by both groups of participants of the pieces in terms of musical characteristics were shared. The implications of this study are as follows. (1) Psychologists and music researchers gain insights about Chinese young adults’ listening preferences, which might offer implications for future research in the field of psychology; and (2) By enhancing multicultural awareness, music education teachers and researchers should combine different music styles to broaden students’ music horizons.

Abstract Background Activated phosphoinositide3-kinase (PI3K) δ syndrome 1 (APDS1) is a novel inborn errors of immunity (IEIs) caused by heterozygous gain of function mutations in PI3Kδ catalytic p110δ (PIK3CD). APDS1 has a spectrum of clinical manifestations. Recurrent respiratory infections, lymphoproliferation, hepatosplenomegaly, hyper-IgM syndrome and autoimmunity are the common symptoms of this disease. Case Presentation Patient 1 presented with recurrent respiratory infections, hepatosplenomegaly and hyper-IgM syndrome. Patient 2 developed early onset systemic lupus erythematosus (SLE)-like disease with resistant thrombocytopenia. c.3061 G > A and c.2314G > A variants in the PIK3CD gene were detected by whole exome sequencing in two patients respectively. c.2314G > A variant in PIK3CD gene of patient 2 is a newly report. After genetic diagnosis, two patients received sirolimus treatment and sirolimus alleviated clinical manifestations, including hepatosplenomegaly in patient 1 and thrombocytopenia in patient 2. Conclusion Genetics diagnosis should be considered in patients with complicated clinical manifestations with no or insufficient response to the conventional therapies. If whole exome sequencing suggests a variant in PIK3CD gene, sirolimus may relieve hepatosplenomegaly and resistant thrombocytopenia. This is the first report of c.2314G > A variant in PIK3CD gene.

Abstract Background Chronic active Epstein–Barr virus infection (CAEBV) and Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) are rare but life-threatening progressive diseases triggered by EBV infection. Glucocorticoid/immunosuppressants treatment is temporarily effective; however, most patients relapse and/or progress. Hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy; however, there are risks of transplantation-associated complications. Currently there is no standard treatment for CAEBV and EBV-HLH. Programmed death protein 1 (PD-1) inhibitors have achieved a high response in many EBV-related diseases. Sintilimab (a recombinant human IgG4 monoclonal antibody against PD-1) disrupts the interaction between PD-1 and its ligand, leading to T cell reinvigoration. Methods A retrospective analysis was performed on three children with CAEBV or EBV-HLH in the Children’s Hospital of Soochow University between 12 December 2020 and 28 November 2022. The efficacy of sintilimab was evaluated. Results Three patients, including two males and one female, were analyzed. Among them, two children were diagnosed with CAEBV with intermittent fever for more than four years, and one child was diagnosed with EBV-HLH. After sintilimab treatment and a mean follow-up of 17.1 months (range 10.0–23.3 months), patients 1 and 3 achieved a complete clinical response and patient 2 achieved a partial clinical response. All three children showed a > 50% decrease in EBV-DNA load in both blood and plasma. EBV-DNA copies in sorted T, B, and NK cells were also markedly decreased after sintilimab treatment. Conclusion Our data supported the efficacy of PD-1 targeted therapy in certain patients with CAEBV and EBV-HLH, and suggested that sintilimab could provide a cure for these diseases, without HSCT. More prospective studies and longer follow-up are needed to confirm these conclusions.

Abstract Native mass spectrometry (MS) is a powerful technique for interrogating membrane protein complexes and their interactions with other molecules. A key aspect of the technique is the ability to preserve native-like structures and noncovalent interactions, which can be challenging depending on the choice of detergent. Different strategies have been employed to reduce charge on protein complexes to minimize activation and preserve non-covalent interactions. Here, we report the synthesis of a class of polyamine detergents tailored for native MS studies of membrane proteins. These detergents, a series of spermine covalently attached to various alkyl tails, are exceptional charge-reducing molecules, exhibiting a ten-fold enhanced potency over spermine. Addition of polyamine detergents to proteins solubilized in maltoside detergents results in improved, charge-reduced native mass spectra and reduced dissociation of subunits. Polyamine detergents open new opportunities to investigate membrane proteins in different detergent environments that have thwarted previous native MS studies.

To address the shortcomings in the drawing and processing of comprehensive characteristic curves of hydraulic turbines and the problems in the operation and management of small hydropower stations, this paper proposes a method for reconstructing the comprehensive characteristic curves based on classification weight neural network. Firstly, this study discretizes the comprehensive characteristic curve of the target turbine factory package to obtain multiple sets of discrete data points, and compares them with the actual operating data of small hydropower plants, and then pre-processes the operating data by the type and operating characteristics of the unit. Next, this paper uses XGBoost to classify the two types of data to obtain the leaf node optimal scores and uses the scores as the prediction weights of the deep neural network to grid the discrete points of the hydraulic turbine for prediction, and finally obtains the specific integrated characteristic graph of the unit. The method based on classification weight neural network can substantially improve the accuracy and reliability of composite characteristic curves while avoiding multivariate nonlinear mathematical problems, which provides a new method and idea for the reconstruction and expansion of the hydraulic turbine characteristic curve, and also provides a theoretical basis for the safe and economic operation of hydropower units.

Flight control law parameters should be designed to provide a sufficient stability margin for closed-loop aircraft while ensuring command tracking accuracy. The singular perturbation margin (SPM) and generalized gain margin (GGM), which are generalizations of the classical phase margin (PM) and gain margin (GM), respectively, from a linear time-invariant system to a nonlinear time-varying system, can be used to quantitatively characterize the maximum singular perturbation and regular perturbation allowed to maintain system stability. In this paper, the sliding mode flight control structure and the design parameters of the sliding mode control law are first introduced for an oblique wing aircraft (OWA), the SPM-gauge and GGM-gauge are added to this closed-loop aircraft model, and the analytical expressions of the SPM and GGM are derived with respect to the control law parameters. Second, the stability margin design requirements of closed-loop aircraft in flight control system design specifications are converted into limitations on the SPM and GGM to determine the value range of the flight control law parameters. Then, with the goal of reducing the sum of the approaching time and sliding time, the parameter value combination is selected within the control law parameter range that meets the stability margin requirements, thus forming a flight control law design method for OWA during the wing skewing process. Finally, the designed control law parameters are applied to a sample OWA, and the stability margin of closed-loop aircraft during the wing skewing process is verified.

Objective: Leptin (LEP) is an obesity-associated adipokine associated with tumor cell growth. We examined the relevance of genetic variants of LEP and leptin receptor (LEPR) to colorectal cancer (CRC) survival by using data from the Newfoundland Familial Colorectal Cancer Study. Methods: A total of 532 patients newly diagnosed with CRC between 1997 and 2003 were followed up until April 2010. Data on their demographics and lifestyles were collected via questionnaires. Genotyping of blood samples was performed with the Illumina Human Omni-Quad Bead chip. Multivariable Cox models were used to assess the relationships of 35 tag single-nucleotide polymorphisms (SNPs) in LEP and LEPR with overall survival (OS), disease-free survival (DFS), and CRC-specific survival. Results: At the gene level, LEP was associated with DFS (P = 0.017), and LEPR was associated with both DFS (P = 0.021) and CRC-specific survival (P = 0.013) in patients with CRC. In single-SNP analysis, LEP rs11763517, LEPR rs9436301, and LEPR rs7602 were associated with DFS after adjustment for multiple testing. The LEPR haplotypes G-C-T (rs7534511-rs9436301-rs1887285) and A-A-G (rs7602-rs970467-rs9436748) were associated with prolonged OS among patients with CRC overall (G-C-T: HR, 0.63; 95% CI, 0.43–0.93; A-A-G: HR, 0.59; 95% CI, 0.38–0.91) and those diagnosed with colon cancer (G-C-T: HR, 0.54; 95% CI, 0.34–0.86; A-A-G: HR, 0.49; 95% CI, 0.29–0.83). Similar results were observed for DFS. Moreover, significant interactions were found among LEPR rs7602 (A vs. G), LEPR rs1171278 (T vs. C), red meat intake, and BMI status: the associations between these variants and prolonged DFS were limited to patients with below-median red meat consumption and body mass index (BMI) < 25 kg/m2. Conclusions: Polymorphic variations in the LEP and LEPR genes were associated with survival of patients after CRC diagnosis. The LEP/LEPR-CRC survival association was modified by participants’ red meat intake and BMI.

Abstract Objective This study examined the dental care utilization and self-preserved dental health of Asian immigrants relative to non-immigrants in Canada. Factors associated with oral health-related disparities between Asian immigrants and other Canadians were further examined. Methods We analyzed 37,935 Canadian residents aged 12 years and older in the Canadian Community Health Survey 2012–2014 microdata file. Factors (e.g., demographics, socioeconomic status, lifestyles, dental insurance coverage, and year of immigration) associated with disparities in dental health (e.g., self-perceived teeth health, dental symptoms during past one month, and teeth removed due to decay in past one year) and service utilization (e.g., visiting dentist within the last three years, visiting dentist more than once per year) between Asian immigrants and other Canadians were examined using multi-variable logistic regression models. Results The frequency of dental care utilization was significantly lower in Asian immigrants than their non-immigrant counterparts. Asian immigrants had lower self-perceived dental health, were less likely to be aware of recent dental symptoms, and more likely to report tooth extractions due to tooth decay. Low education (OR = 0.42), male gender(OR = 1.51), low household income(OR = 1.60), non-diabetes(OR = 1.87), no dental insurance(OR = 0.24), short immigration length (OR = 1.75) may discourage Asian immigrants from dental care utilization. Additionally, a perceived lack of necessity to dentist-visiting was a crucial factor accounting for the disparities in dental care uptake between Asian immigrants and non-immigrants. Conclusion Asian immigrants showed lower dental care utilization and oral health than native-born Canadians.

The threat to global health caused by three highly pathogenic human coronaviruses (HCoV), SARS-CoV-2, MERS-CoV and SARS-CoV, calls for the development of pan-HCoV therapeutics and vaccines. This study reports the design and engineering of a recombinant protein designated HR1LS. It contains three linked molecules, each consisting of three structural domains, including a heptad repeat 1 (HR1), a central helix (CH), and a stem helix (SH) region, in the S2 subunit of SARS-CoV-2 spike (S) protein. It was found that HR1LS protein automatically formed a trimer able to bind with heptad repeat 2 (HR2) region in the SARS-CoV-2 S2 subunit, thus potently inhibiting HCoV fusion and entry into host cells. Furthermore, immunization of mice with HR1LS, when combined with CF501 adjuvant, resulted in the production of neutralizing antibodies against infection of SARS-CoV-2 and its variants, as well as SARS-CoV, MERS-CoV, HCoV-229E, HCoV-NL63 and MjHKU4r-CoV-1. These results suggest that HR1LS is a promising candidate for further development as a novel HR1-trimer-based pan-HCoV entry inhibitor or vaccine for the treatment and prevention of infection by SARS-CoV-2 and its variants, but also other HCoVs with the potential to cause future emerging and re-emerging infectious coronavirus diseases.

ABSTRACTContinuous emergence of the Omicron variant, along with its subvariants, has caused an increasing number of infections, reinfections, and vaccine-breakthrough infections, seriously threatening human health. Recently, several new Omicron subvariants, such as BA.5, BA.2.75, BA.4.6, and BF.7, bearing distinct mutation profiles in their spike (S) proteins, have significantly increased their capacity to evade vaccine-induced immunity and have shown enhanced infectivity and transmissibility, quickly becoming dominant sublineages. In this study, we found the S proteins of these Omicron subvariants to have 2- to 4-fold more efficient membrane fusion kinetics than that of the original Omicron variant (BA.1), indicating that these novel Omicron subvariants might possess increased pathogenicity. We also identified that peptide-based pan-CoV fusion inhibitors, EK1 and EK1C4, showed equal efficacy against membrane fusion mediated by S proteins of the noted Omicron subvariants and infection by their pseudoviruses. Additionally, either immune sera induced by wild-type (WT) SARS-CoV-2 RBD-based vaccine or BA.2 convalescent sera showed potent synergism with EK1 against both WT SARS-CoV-2 and various Omicron subvariants, further suggesting that EK1-based fusion inhibitors are promising candidates for development as clinical antiviral agents against the currently circulating Omicron subvariants.

Abstract Introduction Propofol is the main drug used to induce sedation for endoscopic procedures, and few drugs had shaken its dominant clinical use for a decade until the development of remimazolam. Remimazolam has been demonstrated to perform well in post-marketing studies on sedation for colonoscopy or other procedures requiring short periods of sedation. This study aimed to establish whether remimazolam was effective and safe for inducing sedation for hysteroscopy. Methods One hundred patients who were scheduled to undergo hysteroscopy were randomly assigned to receive induction with remimazolam or propofol. A dose of 0.25 mg/kg remimazolam was administered. Propofol was started at 2–2.5 mg/kg. Before remimazolam or propofol induction, 1 μg/kg fentanyl was infused. Hemodynamic parameters, vital signs, and bispectral index (BIS) values were measured and adverse events recorded to evaluate safety. We comprehensively evaluated the efficacy and safety of the two drugs by the success rate of induction, fluctuation of vital signs, depth of anesthesia, adverse reactions, recovery time, and other indicators. Results Information on 83 patients was successfully recorded and carefully documented. The success rate of sedation in the remimazolam group (group R) was 93%, which was lower than for the propofol group (group P) (100%), but there was no statistically significant difference between the two groups. The incidence of adverse reactions in group R (7.5%) was significantly lower than that in group P (67.4%), and the results were statistically significant (P

Abstract Background Betel nut chewing plays a role in the pathogenesis of oral submucous fibrosis (OSF) and oral squamous cell carcinoma (OSCC). As the major active ingredient of the betel nut, the effect of arecoline and its underlying mechanism to OSF and OSCC pathogenesis remain unclear. Methods Next-generation sequencing-based transcriptome and dRRBS analysis were performed on OSF and OSCC cells under low-dose arecoline exposure. Functional analyses were performed to compare the different roles of arecoline during OSF and OSCC pathogenesis, and key genes were identified. Results In this study, we identified that low-dose arecoline promoted cell proliferation of both NFs and OSCC cells via the acceleration of cell cycle progression, while high-dose arecoline was cytotoxic to both NFs and OSCC cells. We performed for the first time the transcriptome and methylome landscapes of NFs and OSCC cells under low-dose arecoline exposure. We found distinct transcriptome and methylome profiles mediated by low-dose arecoline in OSF and OSCC cells, as well as specific genes and signaling pathways associated with metabolic disorders induced by low-dose arecoline exposure. Additionally, low-dose arecoline displayed different functions at different stages, participating in the modulation of the extracellular matrix via Wnt signaling in NFs and epigenetic regulation in OSCC cells. After exposure to low-dose arecoline, the node roles of FMOD in NFs and histone gene clusters in OSCC cells were found. Meanwhile, some key methylated genes induced by arecoline were also identified, like PTPRM and FOXD3 in NFs, SALL3 and IRF8 in OSCC cells, indicating early molecular events mediated by arecoline during OSF and OSCC pathogenesis. Conclusions This study elucidated the contribution of low-dose arecoline to OSF and OSCC pathogenesis and identified key molecular events that could be targeted for further functional studies and their potential as biomarkers.

Abstract Background China has a double burden of diabetes mellitus and tuberculosis. Diabetes mellitus and tuberculosis are both important risk factors for Aspergillus infection. Aspergillus lentulus is an emerging fungal pathogen in China and invasive aspergillosis due to A. lentulus is associated with high mortality. Case presentation A 79-year-old man was admitted to our hospital, complaining of a 7-day history of fever. Five days before admission, he was diagnosed with pulmonary infection at a local hospital, but his symptoms did not relieve after antibiotic therapy. The patient was diagnosed with diabetes mellitus two months ago. About 20 days ago, he began to present chest tightness and shortness of breath after physical activity. After admission, he developed continuous fever and rapid respiratory deterioration, and finally died after his family abandoned treatment. Pulmonary coinfection with M. tuberculosis and A. lentulus was identified by metagenome next-generation sequencing (mNGS) from bronchoalveolar lavage fluid. Conclusions Clinicians and laboratories should be alert to the emerging A. lentulus infection in China due to its drug-resistance and high mortality. In comparison with conventional methods, mNGS has a great advantage for the diagnosis of mixed pulmonary infection.

ObjectivesType 2 diabetes mellitus(T2DM) and hypertension(HTN) are common comorbidities, and known to affect the brain. However, little is known about the effects of the coexisting HTN on brain in T2DM patients. So we aim to investigate the impact of HTN on the subcortical nucleus morphological alternations in T2DM patients.Materials & methodsThis work was registered by the clinicaltrials.gov (grant number NCT03564431). We recruited a total of 92 participants, comprising 36 only T2DM patients, 28 T2DM patients with HTN(T2DMH) and 28 healthy controls(HCs) in our study. All clinical indicators were assessed and brain image data was collected for each participant. Voxel-based morphometry(VBM), automatic volume and vertex-based shape analyses were used to determine the subcortical nucleus alternations from each participant’s 3D-T1 brain images and evaluate the relationship between the alternations and clinical indicators.ResultsT2DMH patients exhibited volumetric reduction and morphological alterations in thalamus compared to T2DM patients, whereas T2DM patients did not demonstrate any significant subcortical alterations compared to HCs. Furthermore, negative correlations have been found between thalamic alternations and the duration of HTN in T2DMH patients.ConclusionOur results revealed that HTN may exacerbate subcortical nucleus alternations in T2DM patients, which highlighted the importance of HTN management in T2DM patients to prevent further damage to the brain health.

Objective: Metformin is a widely used drug, with a good safety profile, for treatment of type 2 diabetes. Recently, it has been found to also exhibit immunomodulatory potential. We aim to preliminarily explore the potential role of metformin in regulating innate immunity using UM-HET3 mice. Methods: In this study, we treated juvenile UM-HET3 mice with metformin and investigated the alteration of the innate immune response. Peripheral blood of HET3 mice was treated with ex-vivo lipopolysaccharide (LPS) stimulation to induce a leukocyte inflammatory response, which was detected by analyzing the expression of LPS receptors TLR4 and CD14 on leukocytes with flow cytometry. Furthermore, cytokine release induced by LPS was measured in isolated cell culture supernatants with ELISA. Results: In this study LPS treatment triggered a downregulation of TLR4 as well as an upregulation of CD14 expressed on the cell surface. Besides, it enhanced the secretion of pro-inflammatory cytokines TNF-α, IL-1β and IL-6. The results showed that metformin treatment led to a significant ( p < .05) increase in the expression of CD14 and pro-inflammatory cytokines, including IL-1β and IL-6, as well as increased proportion of TLR4 downregulation on the cell surface in response to LPS, specifically in males. Conclusions: This study indicates that treating juvenile mice with metformin enhances the innate immune response to bacterial endotoxin in males, but not in females.

ObjectiveTo examine the incidence and phenotypes of congenital heart disease (CHD) in a large cohort of patients with Hirschsprung's disease (HSCR).Study designRetrospective data review of children with HSCR between 2003 and 2020 was conducted at the Provincial Key Laboratory for Structural Birth Defects in Guangzhou, Guangdong, China. HSCR was confirmed by pathological diagnosis. CHD was defined as a gross structural abnormality of the heart or intrathoracic great vessels that is of functional significance.ResultsA total of 2,174 HSCR patients (84.7% males) were studied and 306 of them underwent echocardiography. Overall, 27 children (1.2%) had associated CHD. Among them, CHDs mostly presented as atrial and ventricular septal defects (n = 5 and 12 respectively) and patent ductus arteriosus (n = 4). Three patients (1.4‰) presented as a severe CHD including complete atrioventricular canal, congenitally corrected transposition of the great arteries and double-outlet of right ventricle. Among 14 patients carrying a chromosomal abnormality, CHD was detected in 4 infants (28.6%), all being mild forms of septal defects.ConclusionsSome new and severe types of CHD were found in patients with HSCR. Patients with syndromic features had higher incidence of CHD.