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Background Endothelin-1 (ET-1) is an endogenous vasoconstrictor implicated in coronary artery disease (CAD) and diabetes. This study aimed to determine the prognostic value of ET-1 in the patients with stable CAD under different glucose metabolism states. Methods In this prospective, large-cohort study, we consecutively enrolled 7,947 participants with angiography-diagnosed stable CAD from April 2011 to April 2017. Patients were categorized by baseline glycemic status into three groups (normoglycemia, prediabetes, and diabetes) and further divided into nine groups by circulating ET-1 levels. Patients were followed for the occurrence of cardiovascular events (CVEs), including nonfatal myocardial infarction, stroke, and cardiovascular mortality. Results Of the 7,947 subjects, 3,352, 1,653, and 2,942 had normoglycemia, prediabetes, and diabetes, respectively. Over a median follow-up of 37.5 months, 381 (5.1%) CVEs occurred. The risk for CVEs was significantly higher in patients with elevated ET-1 levels after adjustment for potential confounders. When patients were categorized by both status of glucose metabolism and plasma ET-1 levels, the high ET-1 levels were associated with higher risk of CVEs in prediabetes (adjusted hazard ratio [HR], 2.089; 95% confidence interval [CI], 1.151 to 3.793) and diabetes (adjusted HR, 2.729; 95% CI, 1.623 to 4.588; both P

Abstract Background Premature infants have less physiologic reserve and often delayed vaccination compared to full-term infants. The birth dose of hepatitis B vaccine (HepB-BD) is an essential measure to achieve the goal of "zero infections" of hepatitis B virus in all newborns. However, there are few investigations of hepatitis B vaccination of preterm infants, leading to uncertainty of coverage and insufficient knowledge of factors influencing timely vaccination of this important population. Methods We obtained hepatitis B vaccine (HepB) vaccination histories of premature infants born during 2019–2021 in three provinces from the respective provincial immunization information systems. Extracted data included date of birth, sex, region, and dates of HepB administration. We conducted descriptive analyses that included basic characteristics of the study subjects, HepB-BD administration, and full-series HepB vaccination. Factors potentially influencing HepB-BD and full series vaccination were analyzed by logistic regression. Results There were 1623 premature infants included in the analytic data set. Overall HepB-BD coverage was 71.41%; coverage among premature infants born to mothers with unknown hepatitis B surface antigen (HBsAg) status was 69.57%; coverage was higher at county-level-and-above hospitals (72.02%) than hospitals below county level (61.11%). Full-series HepB coverage was 94.15%; full-series coverage among preterm infants weighing less than 2000 g at birth was 76.92%. Logistic regression showed that the HepB-BD vaccination rate was positively associated with being born to an HBsAg-positive mother and being preterm with high birth weight. Regression analysis for factors influencing full-series HepB coverage showed that being born prematurely was positively associated with full-series coverage and being premature with a very low birth weight was negatively associated with full-series coverage. Conclusions HepB-BD coverage levels in three provinces of China were less than the target of 90%, especially among premature infants born to mothers with unknown HBsAg status and at hospitals below the county level. Screening of pregnant women should be a universal normal standard. Hepatitis B vaccination training should be strengthened in hospitals to improve the HepB-BD vaccination rate of premature infants and to effectively prevent mother-to-child transmission of hepatitis B virus.

Abstract This study investigated the effect of rubber content on the mechanical characteristics of ultra-high-performance rubberised concrete (UHPRuC). The results revealed a distinctive non-linear decrease in the dry density of UHPRuC as the rubber content increased. Notably, lower rubber content led to a columnar failure mode, while higher content (≥ 20%) exhibited a mixed failure mode with vertical cracking and diagonal fracture. Importantly, the compressive strength showed minimal reduction compared to conventional concrete, presenting a remarkable 50% mitigation of strength reduction compared to previous studies. Utilising reference concrete with robust bond strength proved highly effective in preserving strength in rubberized concrete. Despite its effectiveness in mitigating compressive strength reduction, UHPC could not effectively offset flexural strength loss, which ranged from 1.5 to 3 times that of compressive strength loss. The addition of rubber aggregate in UHPC reduced the peak flexural strength, residual strength, and flexural toughness at a similar rate, while significantly increasing the vibration decaying rate. Incorporating 40% rubber in UHPRuC reduced the eCO2 up to 37%. Our findings emphasise the importance of reference concrete with good bond strength and shows that the addition of rubber aggregate in UHPC leads to reductions in strength but increases the energy-dissipating capacity.

Abstract Pomacea canaliculata is one of the most successful invader in worldwide, adversely affecting native ecosystem through direct predation or indirect competition, while the mechanism of indirect effects on native species remain poorly understood. To clarify the effects of P. canaliculata on the native near-niche species, Bellamya purificata, a widespread freshwater gastropod in China, was selected as the research subject. The changes of mortality, histology, antioxidant system as well as the intestinal flora diversity of B. purificata were explored in present study. The results showed that the median lethal dose of P. canaliculata culture solution for B. purificata was 23.76 ind/L and a concentration-dependent damage of both the gonad and hepatopancreas were observed, the gonadal villi were dissolved and the hepatopancreas cells were broken at 20 ind/L. Furthermore, different concentrations of P. canaliculata culture solution leading to the antioxidant damage on the enzyme or non-enzyme systems of B. purificata at various degrees. Additionally, a decrease in the diversity of the intestinal flora was observed, accompanied by an increase in the abundance of pathogenic bacteria such as Pseudomonas and Aeromonas after the exposure of the culture solution of P. canaliculata. Last, after being recovered in freshwater for 24 h, the antioxidant damage of B. purificata and the disturbance of intestinal flora diversity were still not recovered especially in the high concentration group. The indirect competitive mechanism of P. canaliculata culture solution on B. purificata were explored from the aspects of tissue, biochemical level and intestinal flora, which enriched the research of P. canaliculata invasion on native snails in China, and provided new insights for the study of the invasion strategy of P. canaliculata.

Abstract Porcine pasteurellosis is an infectious disease caused by Pasteurella multocida (P. multocida), which seriously endangers the healthy development of pig breeding industry. Early detection of disease transmission in animals is a crucial early warning for humans. Therefore, predicting risk areas for disease is essential for public health authorities to adopt preventive measures and control strategies against diseases. In this study, we developed a predictive model based on multi-criteria decision analysis (MCDA) and assessed risk areas for porcine pasteurellosis in the Chinese mainland. By using principal component analysis, the weights of seven spatial risk factors were determined. Fuzzy membership function was used to standardize all risk factors, and weight linear combination was used to create a risk map. The sensitivity of the risk map was analyzed by calculating the mean of absolute change rates of risk factors, as well as calculating an uncertainty map. The results showed that risk areas for porcine pasteurellosis were predicted to be locate in the south-central of the Chinese mainland, including Sichuan, Chongqing, Guangdong, and Guangxi. The maximum standard deviation of the uncertain map was less than 0.01and the ROC results showed that the prediction model has moderate predictive performance with the area under the curve (AUC) value of 0.80 (95% CI 0.75–0.84). Based on the above process, MCDA was combined with WebGIS technology to construct a system for predicting risk areas of porcine pasteurellosis. Risk factor data was directly linked to the developed model, providing decision support for disease prevention and control through monthly updates.

Abstract Background The objectives of this study were twofold: (1) to compare gait characteristics between cerebral small vessel disease (CSVD) patients with low-risk oral frailty (OF) and high-risk OF, particularly during dual-task walking (DTW); (2) to investigate the association of OF, the gait characteristics of DTW, and falls among older adults patients with CSVD. Methods A total of 126 hospitalized patients diagnosed with CSVD were recruited and classified into a low-risk group (n = 90) and a high-risk group (n = 36) based on OF status in our study. Comprehensive data pertaining to basic parameters (cadence, as well as stride time, velocity and length), variability, asymmetry, and coordination were gathered during both single-task walking (STW) and DTW. Additionally, the number of falls was calculated. Subsequently, t-test or chi-squared test was used for comparison between the two groups. Furthermore, linear regression analysis was employed to elucidate the association of the OF index-8 score and gait parameters during cognitive DTW. Also, logistic regression models were utilized to assess the independent association of OF risk and falls. Results During cognitive DTW, the high-risk group demonstrated inferior performance in terms of basic parameters (p

Elaeagnus bambusetorum Hand.-Mazz. is a rare plant from China in the Elaeagnaceae family. In this study, we sequenced its complete chloroplast genome. The whole chloroplast genome was 152,265 bp in length, containing a pair of inverted repeats of 25,897 bp, separated by large single copy and small single copy regions of 82,291 bp and 18,180 bp, respectively. The complete genome contained 113 genes, including 79 protein-coding genes, 30 tRNA genes, and 4 rRNA genes. The overall GC content was 37.1%. Phylogenetic analysis using the whole chloroplast genome revealed that E. bambusetorum is sister to E. loureirii and E. conferta. Our study provides valuable insights into the genetic information of E. bambusetorum, which may have important implications for species conservation.

Objectives: To investigate the clinical and molecular epidemiological characteristics of blaIMP-4-carrying Klebsiella pneumoniae in a tertiary hospital in China. Methods: Ten carbapenem-resistant K. pneumoniae (CRKP) isolates carrying the blaIMP-4 gene were collected. Molecular characteristics were analysed using whole-genome sequencing. Plasmid conjugation experiments were used to analyse conjugation of the plasmids. We compared and analysed K. pneumoniae-carrying blaIMP-4 genomic datasets obtained from the National Center for Biotechnology Information (NCBI) with the strains in this study. Results: All 10 CRKP isolates carrying blaIMP-4 were collected from 10 adult patients in the respiratory intensive care unit. These strains were only sensitive to polymyxins and tigecycline due to them simultaneously carrying multiple resistance genes, namely blaOKP-A-5, fosA, oqxA, and oqxB. Notably, R29 harboured two carbapenemase genes (blaNDM-1 and blaIMP-4). These strains had similar drug-resistant phenotypes and genes, all belonging to sequence type (ST)196. Additionally, the patients had experienced spatiotemporal intersection during hospitalization, suggesting that these strains underwent clonal transmission, but they belonged to different clonal clusters from the blaIMP-4-positive K. pneumoniae currently published in the NCBI. Among the 10 strains, blaIMP-4 was located on the IncN plasmid, and six strains had successfully transferred the plasmid to the recipient strain EC600 through plasmid conjugation. Conclusions: The blaIMP-4-positive ST196 CRKP isolate showed clonal distribution in the respiratory intensive care unit, which was mediated by the IncN plasmid. Consequently, there should be increased monitoring of carbapenem-resistant strains in clinical settings to prevent and control its transmission.

Objective: To study the relationship between umbilical cord blood vitamin A (VA) and neonatal lung diseases and explore the impact of umbilical cord blood VA on neonatal lung diseases. Method: Umbilical vein blood was collected at birth, and its VA content was measured. According to the VA levels in umbilical cord blood, a VA deficiency (VAD) group, a marginal deficiency group and a normal group were created and followed up until 28 days after birth. Results: The umbilical cord blood VA level in the neonatal group with lung disease was 0.13 ± 0.05 mg/L, while the result for the VA level in the non-lung disease group was 0.15 ± 0.05 mg/L. The umbilical cord blood VA levels in the neonatal lung disease group were significantly lower than those in the non-lung disease group. The incidence of neonatal pulmonary diseases was highest in the VAD group, and the incidence decreased as the level of VA in umbilical cord blood increased. Umbilical cord blood VAD and premature birth were found to be independent risk factors for neonatal respiratory disease. Conclusion: Umbilical cord blood VAD and premature birth are independent risk factors for neonatal pulmonary diseases. The lower the level of VA in umbilical cord blood, the more susceptible infants will be to neonatal respiratory infections in the neonatal period.

Although serving as the workhorse, MS/MS cannot fully satisfy the analytical requirements of quantitative sub-metabolome characterization. Because more information intrinsically correlates to more structural and concentration clues, here, efforts were devoted to comprehensively tracing and deciphering MS/MS behaviors through constructing triple three-dimensional (3×3D)-MS/MS spectrum. Ginsenosides-targeted metabolomics of notoginseng, one of the most famous edible medicinal plants, was employed as a proof-of-concept. Serial authentic ginsenosides were deployed to build the correlations between 3×3D-MS/MS spectra and structure/concentration features. Through assaying ginsenosides with progressive concentrations using QTOF-MS to configure 1st 3D spectrum, the generations of MS1 spectral signals, particularly multi-charged multimer anions, e.g., [2M–2H]2– and [2M+2HCOO]2– ions, relied on both concentration and the amount of sugar chains. By programming progressive collision energies to the front collision cell of Qtrap-MS device to gain 2nd 3D spectrum, optimal collision energy (OCE) corresponding to the glycosidic bond fission was primarily correlated with the masses of precursor and fragment ions and partially governed by the glycosidation site. The quantitative relationships between OCEs and masses of precursor and fragment ions were utilized to build large-scale quantitative program for ginsenosides. After applying progressive exciting energies to the back collision chamber to build 3rd 3D spectrum, the fragment ion and the decomposition product anion exhibited identical dissociation trajectories when they shared the same molecular geometry. After ginsenosides-focused quantitative metabolomics, significant differences occurred for sub-metabolome amongst different parts of notoginseng. The differential ginsenosides were confirmatively identified by applying the correlations between 3×3D-MS/MS spectra and structures. Together, 3×3D-MS/MS spectrum covers all MS/MS behaviors and dramatically facilitates sub-metabolome characterization from both quantitative program development and structural identification.

The microstructures and cryogenic mechanical properties of dissimilar friction stir welding (FSW) joints between nitrogen-alloyed CoCrFeMnNi high-entropy alloys (HEAs) and Fe–32.1Mn–7.5Cr–0.6Mo–1.2 N steel were investigated. The results reveal that defect-free dissimilar joints can be achieved through FSW. Furthermore, the grains of nitrogen-alloyed CoCrFeMnNi HEAs in the stir zone of the dissimilar joint are significantly more refined than those of Fe–32.1Mn–7.5Cr–0.6Mo–1.2 N steel. Joint efficiency at room and low temperature both exceed 90% of the base metal. Moreover, the cryogenic yield and ultimate strength of the dissimilar joints are higher than those recorded at room temperature. The fracture position is at the heat-affected zone of HEAs under two temperature conditions.

Abstract Background Cystic echinococcosis (CE) is a zoonotic disease caused by the larval stage of the dog tapeworm Echinococcus granulosus sensu lato (E. granulosus), with a worldwide distribution. The current treatment strategy for CE is insufficient. Limited drug screening models severely hamper the discovery of effective anti-echinococcosis drugs. Methods In the present study, using high-content screening technology, we developed a novel high-throughput screening (HTS) assay by counting the ratio of propidium iodide-stained dead protoscoleces (PSCs) to the total number of PSCs. In vitro and ex vivo cyst viability assays were utilized to determine the effect of drugs on cyst viability. Results Using the newly established HTS assay, we screened approximately 12,000 clinical-stage or The Food and Drug Administration (FDA)-approved small molecules from the Repurposing, Focused Rescue, and Accelerated Medchem (ReFRAME) library, as well as the LOPAC1280 and SelleckChem libraries, as a strategic approach to facilitate the drug discovery process. Initial screening yielded 173 compounds with anti-echinococcal properties, 52 of which demonstrated dose–response efficacy against E. granulosus PSCs in vitro. Notably, two agents, omaveloxolone and niclosamide, showed complete inhibition upon further validation in cyst and microcyst viability assays in vitro after incubation for 3 days, and in an ex vivo cyst viability assay using cysts isolated from the livers of mice infected with E. granulosus, as determined by morphological assessment. Conclusions Through the development of a novel HTS assay and by repurposing libraries, we identified omaveloxolone and niclosamide as potent inhibitors against E. granulosus. These compounds show promise as potential anti-echinococcal drugs, and our strategic approach has the potential to promote drug discovery for parasitic infections. Graphical Abstract

Abstract Epigenetic alterations, such as those in chromatin structure and DNA methylation, have been extensively studied in a number of tumor types. But oral cancer, particularly oral adenocarcinoma, has received far less attention. Here, we combined laser-capture microdissection and muti-omics mini-bulk sequencing to systematically characterize the epigenetic landscape of oral cancer, including chromatin architecture, DNA methylation, H3K27me3 modification, and gene expression. In carcinogenesis, tumor cells exhibit reorganized chromatin spatial structures, including compromised compartment structures and altered gene-gene interaction networks. Notably, some structural alterations are observed in phenotypically non-malignant paracancerous but not in normal cells. We developed transformer models to identify the cancer propensity of individual genome loci, thereby determining the carcinogenic status of each sample. Insights into cancer epigenetic landscapes provide evidence that chromatin reorganization is an important hallmark of oral cancer progression, which is also linked with genomic alterations and DNA methylation reprogramming. In particular, regions of frequent copy number alternations in cancer cells are associated with strong spatial insulation in both cancer and normal samples. Aberrant methylation reprogramming in oral squamous cell carcinomas is closely related to chromatin structure and H3K27me3 signals, which are further influenced by intrinsic sequence properties. Our findings indicate that structural changes are both significant and conserved in two distinct types of oral cancer, closely linked to transcriptomic alterations and cancer development. Notably, the structural changes remain markedly evident in oral adenocarcinoma despite the considerably lower incidence of genomic copy number alterations and lesser extent of methylation alterations compared to squamous cell carcinoma. We expect that the comprehensive analysis of epigenetic reprogramming of different types and subtypes of primary oral tumors can provide additional guidance to the design of novel detection and therapy for oral cancer.

Chlaenius bimaculatus Dejean, 1826 (Coleoptera: Carabidea) is a predator of several lepidopteran pests, including Spodoptera frugiperda, S. litura and Helcystogramma triannulella. However, there has been little research into using C. bimaculatus to control crop pests. In this study, we sequenced the complete mitochondrial genome of C. bimaculatus. The results showed that the entire mitochondrial genome was 16,419 bp and contained 24% GC. 13 protein-coding, 22 transfer RNA, and two ribosomal RNA genes were identified. C. bimaculatus shares the same genetic arrangement and composition as other Coleoptera insects. In addition, phylogenetic analysis revealed that C. bimaculatus is closely related to Diplocheila zeelandica.

The high-temperature molten salt pump is the core equipment in the small modular molten salt reactor with media temperatures up to 700 °C. The cantilever ratio of the molten salt pump is usually large. Excessively large cantilever ratios cause increased deformations and rotational amplitudes at the impeller, thus affecting the operational stability of the main pump; small cantilever ratios cause heavy temperature gradients, thus affecting the structural integrity evaluation. This paper used numerical simulation methods to calculate and analyze the temperature field, stress, and structural integrity, optimized the pump shaft cantilever length of the original scheme based on structural integrity using the dichotomy method, and analyzed the rotor dynamics of the optimization results. The results of this study show that the thermal expansion load caused by the temperature difference has a significant mechanical effect on the structure; the first-order critical speed of the rotor system of the optimized schemes has been improved, and the amplitude of the unbalanced response has been significantly reduced, which not only improves the operational stability of the rotor, also contributes to the compact design of the main pump of a small modular molten salt reactor.

Cerebral venous sinus thrombosis (CVST) and hyperlipidemia are severe complications of L-Asparaginase (L-Asp) during the treatment of B-cell acute lymphoblastic leukemia (B-ALL). Herein, we reported a 9-year-old B-ALL boy who underwent abnormal hypertriglyceridemia and CVST presenting as seizures and disturbance of consciousness twice during the induction therapy. Fortunately, he survived treatment with anticoagulant and lipid-lowering therapy. No thrombophilia-related gene mutation was detected, but a heterozygous mutation in lipoprotein lipase (LPL) gene was identified. His neurological symptoms were managed with short-term anticoagulant therapy and long-term lipid-lowering therapy. This case illustrated the manifestation and potential pathogenesis of CVST and highlighted the essentiality of screening baseline lipid profile and dyslipidemia- and thrombophilia-related gene mutation.

Mg is a typical biodegradable metal widely used for biomedical applications due to its considerable mechanical properties and bioactivity. Biodegradable polymers have attracted great interest owing to their favorable processability and inclusiveness. However, it is challenging for the degradation rates of Mg or polymers to precisely match tissue repair processes, and the significant changes in local pH during degradation hinder tissue repair. The concept of combining Mg with polymers is proposed to overcome the shortcomings of materials, aiming to meet repair needs from various aspects such as mechanics and biology. Therefore, it is essential to systematically understand the behavior of biodegradable Mg/polymer composite (BMPC) from the design, manufacturing, mechanical properties, degradation, and biological effects. In this review, we elaborate on the design concepts and manufacturing strategies of high-strength BMPC, the “structure-function” relationship between the microstructures and mechanical properties of composites, the variation in the degradation rate due to endogenous and exogenous factors, and the establishment of advanced degradation research platform. Additionally, the interplay among composite components during degradation and the biological function of composites under non-responsive/stimuli-responsive platforms are also discussed. Finally, we hope that this review will benefit future clinical applications of “structure-function” integrated biomaterials.

Ion mobility spectrometry (IMS) is a trace detection technique operating at atmospheric pressure. It is widely utilized in various fields, such as explosives and drug detection, chemical warfare agent detection, and biomedical applications, due to its fast response time and high sensitivity. The various of substances can be identified through analyzing the discrepancies in the drift time of charged particles in an electric field. Depending on the polarity of the charged particles, it can operate under either positive or negative ion mode. Currently, the majority of IMS operate in only one detection mode. For example, explosives detection operates under negative ion mode, while drug detection operates under positive ion mode. However, single detection mode system is prone to miss detections because some substances may differentially respond to positive and negative detection modes. Simultaneous detection under both positive and negative ion modes can further enhance detection accuracy. In this study, a dual-drift tube ion mobility spectrometry capable of simultaneously detecting positive and negative ions was constructed using corona discharge ionization source technology and a compact dual ion-gated pulse control circuit. The instrument parameters of IMS were optimized, while simultaneously determined hexogen, methamphetamine and the metabolite of trinitrotoluene (TNT)，2,4-diamino-6-nitrotoluene (2,4-DANT). The optimal experimental conditions were selected as follows: a drift gas flow rate of 600 mL/min, a carrier gas flow rate of 500 mL/min, a drift tube temperature of 100 ℃, and a thermal desorption temperature of 200 ℃. The reduced mobility values of 1.72 cm2/V·s and 1.44 cm2/V·s are obtained through the detection of explosive hexogen (RDX) and drug methamphetamine (MA), respectively. These values agree well with the reported values, thereby proving the reliability of the instrument’s detection. Finally, the performance of the developed instrument was evaluated using 2,4-DANT, this substance that can be detected under both positive and negative ion modes. Production peaks are observed in both modes, and the normalized mobility values for 2,4-DANT are reported as approximately 1.67 cm2/V·s and 1.33 cm2/V·s under positive and negative ion modes, respectively. Through exploring the detection limits for both positive and negative ions, it was revealed that the homemade dual ion mobility spectrometer is capable of simultaneous detection of both positive and negative ions, achieves the lowest detection limits of 200 pg and 260 pg for 2,4-DANT, respectively. Importantly, these detection limits are not significantly compromised by sample division, which underscores the broad applicability and value of the instrument, highlighting its potential in various fields.

In response to thermal runaway (TR) of electric vehicles, recent attention has been focused on mitigation strategies such as efficient heat dredging in battery thermal management. Thermal management with particular focus on battery cooling has been becoming increasingly significant. TR usually happened when an electric vehicle is unpowered and charged. In this state, traditional active battery cooling schemes are disabled, which can easily lead to dangerous incidents due to loss of cooling ability, and advanced passive cooling strategies are therefore gaining importance. Herein, we developed an enhanced thermal radiation material, consisting of ∼1 ​μm thick multilayered nano-sheet graphene film coated upon the heat dissipation surface, thereby enhancing thermal radiation in the nanoscale. The surface was characterized on the nanoscale, and tested in a battery-cooling scenario. We found that the graphene-based coating's spectral emissivity is between 91 ​% and 95 ​% in the mid-infrared region, and thermal experiments consequently illustrated that graphene-based radiative cooling yielded up to 15.1 ​% temperature reduction when compared to the uncoated analogue. Using the novel graphene surface to augment a heat pipe, the temperature reduction can be further enlarged to 25.6 ​%. The new material may contribute to transportation safety, global warming mitigation and carbon neutralization.

Abstract Human immunodeficiency virus (HIV) infection is strongly associated with a heightened incidence of lymphomas. To mirror the natural course of human HIV infection, animal models have been developed. These models serve as valuable tools to investigate disease pathobiology, assess antiretroviral and immunomodulatory drugs, explore viral reservoirs, and develop eradication strategies. However, there are currently no validated in vivo models of HIV‐associated lymphoma (HAL), hampering progress in this crucial domain, and scant attention has been given to developing animal models dedicated to studying HAL, despite their pivotal role in advancing knowledge. This review provides a comprehensive overview of the existing animal models of HAL, which may enhance our understanding of the underlying pathogenesis and approaches for malignancies linked to HIV infection.

Abstract Objective Exploration of the efficacy of treating large indirect inguinal hernias in infants and young children using umbilical double-port laparoscopy combined with extraperitoneal water injection. Methods A retrospective analysis was conducted on 165 cases of primary unilateral large indirect inguinal hernias in infants and young children treated at our hospital from May 2018 to May 2023. Among them, 90 cases underwent umbilical double-port laparoscopic surgery combined with extraperitoneal water injection and high ligation of the hernia sac (Double-Port Group), and another 75 cases underwent conventional three-port laparoscopic high ligation of the hernia sac (Three-Port Group). The two groups were compared in terms of operation time, postoperative pain scores at 24 hours, hospital stay, incision complications, and recurrence within one year after surgery. Results Both groups successfully completed the surgery without any intraoperative complications. The pain score at 24 hours postoperatively was lower in the Double-Port Group compared to the Three-Port Group, and there was no statistically significant difference in operation time, hospital stay, and incision complications between the two groups (P > 0.05). Both groups were followed up for one year postoperatively; the Three-Port Group had one recurrence that was cured after further treatment, while there were no recurrences in the Double-Port Group. Conclusion Umbilical double-port laparoscopy combined with extraperitoneal water injection for the treatment of large indirect inguinal hernias in infants and young children has the advantages of being safe and reliable, with concealed and aesthetic incisions, and rapid recovery.

Abstract Objective We aimed to summarize the association between gestational diabetes mellitus (GDM) and its intergenerational cardiovascular diseases (CVDs) impacts in both mothers and offspring post-delivery in existing literature. Methods PubMed, Embase, Web of Science, and Scopus were utilized for searching publications between January 1980 and June 2024, with data extraction and meta-analysis continuing until 31 July 2024. Based on a predefined PROSPERO protocol, studies published as full-length, English-language journal articles that reported the presence of GDM during pregnancy and its association with any CVD development post-delivery were selected. All studies were evaluated using the Newcastle-Ottawa Scale. Maximally adjusted risk estimates were pooled using random-effects meta-analysis to assess the risk ratio (RR) of GDM, and overall and subtypes of CVDs in both mothers and offspring post-delivery. Results The meta-analysis was based on 38 studies with a total of 77,678,684 participants. The results showed a 46% increased risk (RR 1.46, 95% CI 1.34–1.59) for mothers and a 23% increased risk (1.23, 1.05–1.45) for offspring of developing overall CVDs after delivery, following a GDM-complicated pregnancy. Our subgroup analysis revealed that mothers with a history of GDM faced various risks (20% to 2-fold) of developing different subtypes of CVDs, including cerebrovascular disease, coronary artery disease, heart failure, and venous thromboembolism. Conclusions These findings underscore the heightened risk of developing various CVDs for mothers and offspring affected by GDM, emphasizing the importance of preventive measures even right after birth to mitigate the burden of CVDs in these populations.

Abstract Background Chinese patent medicines (CPMs) are widely used in China as an adjuvant treatment in dilated cardiomyopathy with heart failure (DCM-HF). However, comprehensive and systematic evidence supporting the beneficial effects of CPMs combined with current complementary and alternative medicine (CAM) treatments against DCM-HF was limited. This network meta-analysis (NMA) aimed to assess and rank the relative efficacy of eight different CPMs for DCM-HF. Methods To retrieve randomized controlled trials (RCTs) focusing on the use of CPMs combined with CAM for DCM-HF, the databases of PubMed, Embase, Web of Science Core Collection, Cochrane Library, ProQuest, China National Knowledge Infrastructure (CNKI), China Science Periodical Database (CSPD), Chinese Citation Database (CCD), Chinese Biomedical Literature Database (CBM), and ClinicalTrials.gov were comprehensively searched from their inception to 29 February 2024. The quality of the included RCTs was examined using the Cochrane Risk of Bias assessment tool, version 2.0 (RoB 2). Surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the relative efficacy. Bayesian network meta-analysis was designed to assess the efficacy of different CPMs. Results After applying the inclusion and exclusion criteria, a total of 77 eligible RCTs involving 6980 patients were enrolled. The outcomes assessed included clinical effectiveness rate (CER), left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD), 6-min walk test (6MWT), brain natriuretic peptide (BNP), and cardiac output (CO). The results of the NMA indicated that Qili Qiangxin capsule (QLQX), Wenxin granule (WX), Tongxinluo capsule (TXL), Qishen Yiqi dropping pill (QSYQ), Shexiang Baoxin pill (SXBX), Yangxinshi tablet (YXST), Yixinshu capsule (YXSC), and Getong Tongluo capsule (GTTL) combined with CAM significantly improved performance compared with CAM alone in treating DCM-HF. YXST + CAM (MD = − 9.93, 95% CI − 12.83 to − 7.03) had the highest probability of being the best treatment on account of the enhancement of LVEF. WX + CAM had the highest likelihood of being the best treatment considering the improvement in LVEDD (MD = − 11.7, 95% CI − 15.70 to − 7.79) and 6MWT (MD = − 51.58, 95% CI − 73.40 to − 29.76). QLQX + CAM (MD = − 158.59, 95% CI − 267.70 to − 49.49) had the highest likelihood of being the best intervention for the reduction in BNP. TXL + CAM (MD = − 0.93, 95% CI − 1.46 to − 0.40) might be the optimal choice for increasing CO levels in DCM-HF patients. No serious treatment-emergent adverse events were observed. Conclusion This NMA suggested that adding CPMs to the current CAM treatment exerted a more positive effect on DCM-HF. Thereinto, QLQX + CAM, TXL + CAM, WX + CAM, and YXST + CAM showed a preferable improvement in patients with DCM-HF when unified considering the clinical effectiveness rate and other outcomes. Furthermore, due to the lack of information on CPMs against DCM-HF and the uneven distribution of included studies among interventions, more high-quality studies are needed to provide more robust evidence to support our findings. Systematic review registration PROSPERO (CRD42023482669).

Abstract Policies to address climate change have been implemented worldwide in recent years. The core of these policies is to control greenhouse gas (GHG) emissions, which primarily stem from the consumption of fossil fuels. Consequently, the implementation of climate policies can affect other energy-related issues, such as energy poverty, a critical element of the UN Sustainable Development Goals (SDGs). This paper uses cross-country data from 2000 to 2020 to study the possible policy spillovers from climate actions to energy poverty. We show that a spillover effect does exist. In other words, a higher number of climate policies is associated with a lower level of energy poverty. The spillover is realized through improvements in energy efficiency, the promotion of renewable energy, and support for innovations. In addition, legislative policies are found to have stronger spillover effects. While the overall policy effects are positive for executive policies, regulations tend to have negative impacts on energy development. There is also evidence demonstrating heterogeneous effects between long-term and short-term policies, and between developed and developing countries. Discovering this spillover effect gives extra motivation for countries to adopt climate policies and actively seek synergies in achieving broader sustainable goals.

Abstract Due to the repeated changes in the COVID-19 pandemic, we live in an era of various uncertainties that raise future anxiety and behavioral addiction problems. According to the Protection Motivation Theory (PMT), the present study attempted to explore the impact of COVID-19 intolerance of uncertainty (COVID-19 IU) on internet addiction (IA) among college students and the mediating role of future anxiety (FA) by constructing a mediating model. A questionnaire survey was conducted on 679 Chinese college students and PROCESS 3.5 was utilized to test the hypotheses. The results indicated that the COVID-19 IU was significantly positively correlated with IA and FA, and FA was significantly positively correlated with IA. COVID-19 IU had a significant positive predictive effect on IA; FA played a complementary partial mediating role between COVID-19 IU and IA. The results supported the PMT, which not only enriched our understanding of FA under uncertain life circumstances, but also deepened our understanding of the potential mechanisms of the effects of IA. Finally, discussions and suggestions were presented based on the results.

Abstract Hydrogen sulfide is essential in numerous physiological and pathological processes and has emerged as a promising cancer imaging and signaling molecule and a potentially versatile therapeutic agent. However, the endogenous levels of hydrogen sulfide remain insufficient to perform its biological functions, and thus, developing novel strategies that amplify hydrogen sulfide signals at lesion sites is of increasing interest. In this work, a nanoplatform (SNP) based on hydrogen sulfide-responsive self-immolative poly(thiocarbamate) with localized hydrogen sulfide signal amplification capability is developed to encapsulate a hydrogen sulfide-responsive fluorescent probe (e.g., hemicyanine dye; p-Cy) or an anticancer prodrug (e.g., doxorubicin; p-DOX) to form a nanoprobe (SNPp-Cy) or nanomedicine (SNPp-DOX) for cancer imaging and therapy, respectively. SNPp-Cy exhibits a low detection limit for hydrogen sulfide, enabling ultrasensitive detection of small (

Abstract Background The national volume-based procurement (NVBP) policy has significantly decreased prices and increased the accessibility of NVBP drugs. Nevertheless, issues such as heightened adverse reactions and suboptimal efficacy have arisen. Concerns regarding the quality of low-cost medications and the absence of long-term research have been widely recognized. This has led to caution among patients with late-life depression (LLD) due to their delicate health and the severity of their condition. This study evaluated the choice intention for NVBP drugs and associated factors in older patients with LLD. Methods A weighted sample of 408 participants between December 2022 and March 2023 were included. Data were collected via face-to-face interviews and questionnaires. To identify significant associated factors of choice intention, a multilevel logistic regression model was employed. Results Over half (53.68%) of older patients with LLD intended to choose NVBP drugs. Associated factors included self-assessed poor economy, higher out-of-pocket expenses, monthly household income exceeding CNY 6000, absence of other non-communicable chronic diseases, ordinary registration, urban employee medical insurance, no requirements for brand-name drugs, adverse reactions after using NVBP drugs, and rejection of physicians’ recommendation for NVBP drugs. The interaction effect between the real economic condition and patients self-assessed economy significantly influences choice intention for NVBP drugs. Among 124 patients with self-assessed poor economy, 75 showed a higher intention to use NVBP drugs. In these patients, age, medical insurance reimbursement, and brand awareness were significantly associated with choice intention. Conclusion Economic factors, physical conditions, medical needs, and physician recommendations significantly influenced the choice intention for NVBP drugs. The choice intention can be improved by strengthening physician-patient communication, increasing the scope and proportion of medical insurance reimbursement, improving substitution studies, and conducting post-marketing re-evaluations of NVBP drugs.

Abstract BCL-2 inhibitors such as venetoclax offer therapeutic promise in acute myeloid leukemia (AML) and other cancers, but drug resistance poses a significant challenge. It is crucial to understand the mechanisms that regulate venetoclax response. While correlative studies have identified numerous genes linked to venetoclax sensitivity, their direct impact on the drug response remains unclear. In this study, we targeted around 1400 genes upregulated in venetoclax-sensitive primary AML samples and carried out a CRISPR knockout screen to evaluate their direct effects on venetoclax response. Our screen identified the transcription factor ZNF740 as a critical regulator, with its expression consistently predicting venetoclax sensitivity across subtypes of the FAB classification. ZNF740 depletion leads to increased resistance to ventoclax, while its overexpression enhances sensitivity to the drug. Mechanistically, our integrative transcriptomic and genomic analysis identifies NOXA as a direct target of ZNF740, which negatively regulates MCL-1 protein stability. Loss of ZNF740 downregulates NOXA and increases the steady state protein levels of MCL-1 in AML cells. Restoring NOXA expression in ZNF740-depleted cells re-sensitizes AML cells to venetoclax treatment. Furthermore, we demonstrated that dual targeting of MCL-1 and BCL-2 effectively treats ZNF740-deficient AML in vivo. Together, our work systematically elucidates the causal relationship between venetoclax response signature genes and establishes ZNF740 as a novel transcription factor regulating venetoclax sensitivity.

Abstract Background The diagnosis of tuberculous pleurisy (TP) presents a significant challenge due to the low bacterial load in pleural effusion (PE) samples. Cell-free Mycobacterium tuberculosis DNA (cf-TB) in PE samples is considered an optimal biomarker for diagnosing TP. This study aimed to evaluate the applicability of cf-TB testing across diverse research sites with a relatively large sample size. Methods Patients suspected of TP and presenting with clinical symptoms and radiological evidence of PE were consecutively enrolled by treating physicians from 11 research sites across 6 provinces in China between April 2020 and August 2022. Following centrifugation, sediments obtained from PE were used for Xpert MTB/RIF (Xpert) and mycobacterial culture, while the supernatants were subjected to cf-TB testing. This study employed a composite reference standard to definite TP, which was characterized by any positive result for Mycobacterium tuberculosis (MTB) through either PE culture, PE Xpert, or pleural biopsy. Results A total of 1412 participants underwent screening, and 1344 (95.2%) were subsequently enrolled in this study. Data from 1241 (92.3%) participants were included, comprising 284 with definite TP, 677 with clinically diagnosed TP, and 280 without TP. The sensitivity of cf-TB testing in definite TP was 73.6% (95% CI 68.2–78.4), significantly higher than both Xpert (40.8%, 95% CI 35.3–46.7, P

Abstract Quantum metrology promises unprecedented precision of parameter estimation, but it is often vulnerable to noise. While significant efforts have been devoted to improving the metrology performance in Markovian environments, practical control schemes specifically designed for non-Markovian noises are much less investigated. Here, we propose two control-enhanced quantum metrology schemes that are suitable for tackling general non-Markovian noises described by noise channels or noise spectra. We conduct experiments to verify the efficacy of these schemes on a nuclear magnetic resonance system. The experimental results involving multiqubit probes show that the parameter estimation precision can be greatly improved, significantly surpassing the standard quantum limit, with our schemes. At present, non-Markovian noises are widely encountered on diverse quantum devices, the proposed schemes are relevant for realistic metrology applications on these platforms.

Abstract Background This study aims to analyse changes in urinary kidney injury markers in children with Mycoplasma pneumoniae pneumonia (MPP), investigate the risk factors for MPP-related acute kidney injury (AKI) and establish a model to predict MPP-related AKI. Methods Ninety-five children were enrolled based on the study’s inclusion and exclusion criteria. They were divided into a severe MPP (SMPP) group and a non-SMPP group and then into an AKI group and a non-AKI group according to the presence of AKI. A univariate logistic regression analysis was performed to explore the early risk factors for AKI. Based on a multivariate logistic regression analysis and a least absolute shrinkage and selection operator regression analysis, appropriate variables were selected to establish a prediction model, and R 4.2.2 software was used to draw nomograms and generate a dynamic nomogram website. Results Seven urinary kidney injury markers were abnormally elevated in the SMPP group and the non-SMPP group: urinary N-acetyl-β-D-glucosaminidase (NAG), β2-microglobulin, α1-microglobulin, retinol-binding protein, urinary immunoglobulin G, urinary transferrin and urinary microalbumin. Sixteen children were identified with AKI during hospitalisation. The AKI group had higher levels of urinary NAG, α1-microglobulin, β2-microglobulin, urinary microalbumin, urinary transferrin and retinol-binding protein than the non-AKI group (P

Abstract The high‐voltage pulse discharge technology, which is based on the electrohydraulic effect, can generate powerful, controllable, and repetitive electrohydraulic shock waves (EHSWs) in underground confined space, so it has been applied in the petroleum industry to improve the permeable of the reservoir. In this paper, a numerical model based on LS‐DYNA is built to study the damage analysis of the cement sheath and rock subjected to EHSWs during perforation completion. The results show that the stress state of the cement sheath and rock surrounding the perforation hole is determined by the shock pressure from both the perforation hole and the wellbore; the damage of the cement sheath and rock is mainly caused by tensile stress; the damage zone of the cement sheath is mainly distributed on the inner surface and near the perforation hole, while the damage zone of rock is distributed near the perforation hole; after multiple discharges, the damage of cement sheath and rock gradually accumulates, and the damage zone eventually forms a vertical plane along perforation holes. Overall, these results provide guidance for the safe application of the high‐voltage pulse discharge technology in the oil field.

Abstract Spinal cord injury (SCI) presents a critical medical challenge, marked by substantial neural damage and persistent functional deficits. This study investigates the therapeutic potential of cold atmospheric plasma (CAP) for SCI, utilizing a tailored dielectric barrier discharge (DBD) device to conduct comprehensive in vivo and in vitro analyses. The findings show that CAP treatment significantly improves functional recovery after SCI, reduces neuronal apoptosis, lowers inflammation, and increases axonal regeneration. These findings illustrate the efficacy of CAP in fostering a conducive environment for recovery by modulating inflammatory responses, enhancing neuronal survival, and encouraging regenerative processes. The underlying mechanism involves CAP’s reactive oxygen species (ROS) reduction, followed by activating antioxidant enzymes. These findings position CAP as a pioneering approach for spinal cord injury (SCI) treatment, presenting opportunities for improved neural recovery and establishing a new paradigm in SCI therapy.

Abstract Background Epimedin A (EA) has been shown to suppress extensive osteoclastogenesis and bone resorption, but the effects of EA remain incompletely understood. The aim of our study was to investigate the effects of EA on osteoclastogenesis and bone resorption to explore the corresponding signalling pathways. Methods Rats were randomly assigned to the sham operation or ovariectomy group, and alendronate was used for the positive control group. The therapeutic effect of EA on osteoporosis was systematically analysed by measuring bone mineral density and bone biomechanical properties. In vitro, RAW264.7 cells were treated with receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) to induce osteoclast differentiation. Cell viability assays, tartrate-resistant acid phosphatase (TRAP) staining, and immunofluorescence were used to elucidate the effects of EA on osteoclastogenesis. In addition, the expression of bone differentiation-related proteins or genes was evaluated using Western blot analysis or quantitative polymerase chain reaction (PCR), respectively. Results After 3 months of oral EA intervention, ovariectomized rats exhibited increased bone density, relative bone volume, trabecular thickness, and trabecular number, as well as reduced trabecular separation. EA dose-dependently normalized bone density and trabecular microarchitecture in the ovariectomized rats. Additionally, EA inhibited the expression of TRAP and NFATc1 in the ovariectomized rats. Moreover, the in vitro results indicated that EA inhibits osteoclast differentiation by suppressing the TRAF6/PI3K/AKT/NF-κB pathway. Further studies revealed that the effect on osteoclast differentiation, which was originally inhibited by EA, was reversed when the TRAF6 gene was overexpressed. Conclusions The findings indicated that EA can negatively regulate osteoclastogenesis by inhibiting the TRAF6/PI3K/AKT/NF-κB axis and that ameliorating ovariectomy-induced osteoporosis in rats with EA may be a promising potential therapeutic strategy for the treatment of osteoporosis.

Abstract The prevention and treatment of gastrointestinal mucosal injury caused by a plateau hypoxic environment is a clinical conundrum due to the unclear mechanism of this syndrome; however, oxidative stress and microbiota dysbiosis may be involved. The Robinia pseudoacacia L. flower, homologous to a functional food, exhibits various pharmacological effects, such as antioxidant, antibacterial, and hemostatic activities. An increasing number of studies have revealed that plant exosome-like nanoparticles (PELNs) can improve the intestinal microbiota and exert antioxidant effects. In this study, the oral administration of Robinia pseudoacacia L. flower exosome-like nanoparticles (RFELNs) significantly ameliorated hypoxia-induced gastric and small intestinal mucosal injury in mice by downregulating hypoxia-inducible factor-1α (HIF-1α) and HIF-2α expression and inhibiting hypoxia-mediated ferroptosis. In addition, oral RFELNs partially improved hypoxia-induced microbial and metabolic disorders of the stomach and small intestine. Notably, RFELNs displayed specific targeting to the gastrointestinal tract. In vitro experiments using gastric and small intestinal epithelial cell lines showed that cell death caused by elevated HIF-1α and HIF-2α under 1% O2 mainly occurred via ferroptosis. RFELNs obviously inhibited HIF-1α and HIF-2α expression and downregulated the expression of NOX4 and ALOX5, which drive reactive oxygen species production and lipid peroxidation, respectively, suppressing ferroptosis under hypoxia. In conclusion, our findings underscore the potential of oral RFELNs as novel, naturally derived agents targeting the gastrointestinal tract, providing a promising therapeutic approach for hypoxia-induced gastric and small intestinal mucosal ferroptosis. Graphical Abstract

Abstract Background The co-infection of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) and tuberculosis (TB) poses a significant clinical challenge and is a major global public health issue. This study aims to elucidate the disease burden of HIV-TB co-infection in global, regions and countries, providing critical information for policy decisions to curb the HIV-TB epidemic. Methods The ecological time-series study used data from the Global Burden of Disease (GBD) Study 2021. The data encompass the numbers of incidence, prevalence, mortality, and disability-adjusted life year (DALY), as well as age-standardized incidence rate (ASIR), prevalence rate (ASPR), mortality rate (ASMR), and DALY rate for HIV-infected drug-susceptible tuberculosis (HIV-DS-TB), HIV-infected multidrug-resistant tuberculosis (HIV-MDR-TB), and HIV-infected extensively drug-resistant tuberculosis (HIV-XDR-TB) from 1990 to 2021. from 1990 to 2021. The estimated annual percentage change (EAPC) of rates, with 95% confidence intervals (CIs), was calculated. Results In 2021, the global ASIR for HIV-DS-TB was 11.59 per 100,000 population (95% UI: 0.37–13.05 per 100,000 population), 0.55 per 100,000 population (95% UI: 0.38–0.81 per 100,000 population), for HIV-MDR-TB, and 0.02 per 100,000 population (95% UI: 0.01–0.03 per 100,000 population) for HIV-XDR-TB. The EAPC for the ASIR of HIV-MDR-TB and HIV-XDR-TB from 1990 to 2021 were 4.71 (95% CI: 1.92–7.59) and 13.63 (95% CI: 9.44–18.01), respectively. The global ASMR for HIV-DS-TB was 2.22 per 100,000 population (95% UI: 1.73–2.74 per 100,000 population), 0.21 per 100,000 population (95% UI: 0.09–0.39 per 100,000 population) for HIV-MDR-TB, and 0.01 per 100,000 population (95% UI: 0.00–0.03 per 100,000 population) for HIV-XDR-TB in 2021. The EAPC for the ASMR of HIV-MDR-TB and HIV-XDR-TB from 1990 to 2021 were 4.78 (95% CI: 1.32–8.32) and 10.00 (95% CI: 6.09–14.05), respectively. Conclusions The findings indicate that enhancing diagnostic and treatment strategies, strengthening healthcare infrastructure, increasing access to quality medical care, and improving public health education are essential to combat HIV-TB co-infection. Graphical Abstract

This review thoroughly explores the multifaceted roles of sexual hormones, emphasizing their impact beyond reproductive functions and underscoring their significant influence on cardiometabolic regulation. It analyzes the broader physiological implications of estrogen, testosterone, and progesterone, highlighting their effects on metabolic syndrome, lipid metabolism, glucose homeostasis, and cardiovascular health. Drawing from diverse molecular, clinical, and therapeutic studies, the paper delves into the intricate interplay between these hormones and cardiometabolic processes. By presenting a comprehensive analysis that goes beyond traditional perspectives, and recognizing sexual hormones as more than reproductive agents, the review sheds light on their broader significance in health and disease management, advocating for holistic and personalized medical approaches.