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Abstract Background Triglyceride (TG) and its related metabolic indices are recognized as important biomarker gauging cardiovascular diseases. This study aimed to explore the association between multiple TG-derived metabolic indices including the atherogenic index of plasma (AIP), triglyceride-glucose (TyG) index, triglyceride glucose-body mass index (TyG-BMI) and cardiovascular outcomes to identify valuable predictors for cardiovascular prognosis in patients with type 2 diabetes (T2DM) and coronary heart disease (CHD). Methods Data of 1034 patients with T2DM and CHD from China-Japan Friendship Hospital between January 2019 and March 2022 were collected and analyzed. Multivariate Cox proportional hazards models and restricted cubic spline (RCS) analysis were conducted to examine the associations between AIP, TyG index, TyG-BMI and major adverse cardiac and cerebrovascular events (MACCEs). The area under the receiver operating characteristic (ROC) curve (AUC) was used to screen the most valuable predictor. Kaplan-Meier curve analysis was employed to examine the relationship between the predictor and prognosis. The goodness-of-fit of models was evaluated using the calibration curve and χ2 likelihood ratio test. Subgroup analysis and interaction test were performed to control for confounding factors. Results The overall incidence of MACCEs was 31.04% during a median of 13.3 months of follow-up. The results showed that AIP, TyG index and TyG-BMI were all positively correlated with the risk of MACCEs in patients with T2DM and CHD (P

Abstract Nasopharyngeal carcinoma (NPC) presents a significant medical challenge due to its high incidence rate and poor prognosis, which are attributed primarily to tumor metastasis and drug resistance. Sine oculis homeobox homolog 1 (SIX1) has been identified as a crucial target for cancer treatment. However, its role in NPC remains incompletely understood. This study investigated the mechanisms by which the degradation of the SIX1 protein, which is mediated by ubiquitin, affects the malignant characteristics of NPC throughout the cell cycle. Our findings reveal that reduced expression of the itchy E3 ubiquitin ligase E3 (ITCH) in NPC impedes the degradation of the SIX1 protein, leading to enhance oncogenic properties. Knockdown experiments which SIX1 was inhibited demonstrated a decrease in the proliferation, migration, and invasion of NPC cell lines, whereas overexpression of SIX1 yielded the opposite effects. Further experimental validation revealed that SIX1 promotes NPC progression via the cell division cycle 27 (CDC27)/cyclin B1 axis. These findings provide valuable insights into potential therapeutic targets and prognostic indicators for NPC treatment, emphasizing the ITCH/SIX1/CDC27/cyclin B1 axis as a promising target for novel therapies.

Abstract As oil production increasingly transitions from shallow to deep formation, the need for efficient PDC cutters to drill through deep hard rock becomes paramount. Currently, there is a lack of effective methods for optimizing cutter shapes and their cutting parameters. This study addresses this gap by developing a rock-breaking mechanism model for PDC cutters and proposing a Stability Index (SI) based on cutting force variations during the cutting process. Using the FDEM method, we simulated the rock-breaking processes of planar, stinger, and machete cutters under various cutting depths and angles. SI and Mechanical Specific Energy (MSE) were employed as evaluation metrics to analyze the rock-breaking characteristics and determine the optimal cutting parameters for each cutter type. The results indicate that at shallow cutting depths, cutting force changes are minimal, predominantly causing plastic damage to the rock, resulting in lower stress and reduced wear on the PDC cutters. Conversely, at greater cutting depths, significant fluctuations in cutting force occur, leading to brittle failure and the generation of large cuttings. This sudden increase in cutting force can accelerate rock breaking but also increases the risk of cutter wear. Our findings suggest that the planar cutter offers stable performance with high cutting force requirements, optimal at a cutting depth of 1.5 mm and an angle of less than 20°. The stinger cutter, requiring lower cutting forces, performs best at a cutting depth of 2 mm and an angle of 20°. The machete cutter exhibits characteristics similar to the stinger cutter at shallow depths and the planar cutter at deeper depths, making it suitable for drilling at a depth of 2 mm and an angle of less than 10°. By balancing SI and MSE, this study provides a comprehensive approach to optimizing PDC cutter performance, enhancing drilling efficiency while minimizing cutter wear.

Abstract Production of epoxides via selective oxidation of olefins affords a fundamental source of key intermediates for the industrial manufacture of diverse chemical stocks and materials. Current oxidation strategy generally works under harsh conditions including high temperature, high pressure, and/or request for potentially hazardous oxidants, leading to substantial challenges in sustainability and energy efficiency. To this end, direct electrocatalytic epoxidation poses as a promising solution to these issues, yet their industrial applications are limited by the low selectivity, low yield, and poor stability of the electrocatalysts. Here we report a universal electrochemical epoxidation approach via a kinetically confined surface radical pathway. High epoxidation efficiency can be achieved under mild working conditions (e.g., >99% selectivity, >80% yield and >80% Faraday efficiency for cyclohexene-to-cyclohexene oxide conversion), which can be extended to broad scope of olefin substrates. The catalytic performance originated from a surface bimolecular (L-H) reaction mechanism involving formation and surface confinement of bromine radicals due to kinetic restriction, which effectively activates inert C=C bonds while avoiding the homogenous radical side reactions. With the use of renewable energy and water as green oxygen source, successful implementation of this approach will pave the way for more sustainable chemical production and manufacturing.

Abstract The propagation speed of gravitational waves is a fundamental issue in gravitational theory. According to general relativity, gravitational waves propagate at the speed of light. However, alternative theories of gravity propose modifications to general relativity, including variations in the speed of gravitational waves. In this paper, we investigate scalar-induced gravitational waves that propagate at speeds different from the speed of light. First, we analytically calculate the power spectrum of scalar induced gravitational waves based on the speed and spectrum of primordial curvature perturbations. We then explore several scalar power spectra, deriving corresponding fractional energy densities, including monochromatic spectrum, scale-invariant spectrum, and power-law spectrum. Finally, we constrain scalar-induced gravitational waves and evaluate the signatures of their speed from the combination of CMB+BAO and gravitational wave observations. Our numerical results clearly illustrate the influence of the speed of scalar-induced gravitational waves.

Abstract Deep learning algorithms have demonstrated remarkable efficacy in various medical image analysis (MedIA) applications. However, recent research highlights a performance disparity in these algorithms when applied to specific subgroups, such as exhibiting poorer predictive performance in elderly females. Addressing this fairness issue has become a collaborative effort involving AI scientists and clinicians seeking to understand its origins and develop solutions for mitigation within MedIA. In this survey, we thoroughly examine the current advancements in addressing fairness issues in MedIA, focusing on methodological approaches. We introduce the basics of group fairness and subsequently categorize studies on fair MedIA into fairness evaluation and unfairness mitigation. Detailed methods employed in these studies are presented too. Our survey concludes with a discussion of existing challenges and opportunities in establishing a fair MedIA and healthcare system. By offering this comprehensive review, we aim to foster a shared understanding of fairness among AI researchers and clinicians, enhance the development of unfairness mitigation methods, and contribute to the creation of an equitable MedIA society.

Abstract Schizophrenia is a severe psychiatric disorder with high heritability, characterized by positive and negative symptoms as well as cognitive abnormalities. Dysfunction in glutamate synapse is strongly implicated in the pathophysiology of schizophrenia. However, the precise role of the perturbed glutamatergic system in contributing to the cognitive abnormalities of schizophrenia at the synaptic level remains largely unknown. Although our previous work found that Opcml promotes spine maturation and Opcml-deficient mice exhibit schizophrenia-related cognitive impairments, the synaptic mechanism remains unclear. By using whole-cell patch clamp recording, we found that decreased neuronal excitability and alterations in intrinsic membrane properties of CA1 PNs in Opcml-deficient mice. Furthermore, Opcml deficiency leads to impaired glutamatergic transmission in hippocampus, which is closely related to postsynaptic AMPA/NMDA receptors dysfunction, resulting in the disturbances of E/I balance. Additionally, we found that the aripiprazole which we used to ameliorate abnormal cognitive behaviors also rescued the impaired glutamatergic transmission in Opcml-deficient mice. These findings will help to understand the synaptic mechanism in schizophrenia pathogenesis, providing insights into schizophrenia therapeutics with glutamatergic disruption.

In order to reduce the risk of coal mine production, timely predict and control the risk of roadway roof fall, twelve evaluation indexes such as the thickness of stable rock strata, geological conditions and cross-section shape of roadway were selected. The risk evaluation index system of roadway roof fall was constructed, and the risk degree standard of roadway roof fall was proposed. The risk evaluation model of roadway roof fall was established by using the combination weight matter-element extension theory of analytic hierarchy process (AHP) and entropy weight (EW). The risk degree of roadway roof fall was determined according to the principle of maximum membership degree, and the risk assessment system of roadway roof fall (MW-MEW) was developed based on JavaWeb. The evaluation method and MW-MEW system were applied to evaluate the risk degree of roof fall in C9 return air connecting roadway of Xinglu Coal Mine, and the evaluation results were compared with those of AHP-matter element extension model. The results showed that the evaluation results of the evaluation method were in line with the actual engineering situation and were better than the AHP-matter element extension model.

Abstract Thermal quench of a nearly collisionless plasma against an isolated cooling boundary or region is an undesirable off-normal event in magnetic fusion experiments, but an ubiquitous process of cosmological importance in astrophysical plasmas. Parallel transport theory of ambipolar-constrained tail electron loss is known to predict rapid cooling of the parallel electron temperature $$T_{e\parallel },$$ although $$T_{e\parallel }$$ is difficult to diagnose in actual experiments. Instead direct experimental measurements can readily track the perpendicular electron temperature $$T_{e\perp }$$ via electron cyclotron emission. The physics underlying the observed fast drop in $$T_{e\perp }$$ requires a resolution. Here two collisionless mechanisms, dilutional cooling by infalling cold electrons and wave-particle interaction by two families of whistler instabilities, are shown to enable fast $$T_{e\perp }$$ cooling that closely tracks the mostly collisionless crash of $$T_{e\parallel }.$$ These findings motivate both experimental validation and reexamination of a broad class of plasma cooling problems in laboratory, space, and astrophysical settings.

Abstract Background Ferroptosis, a non-apoptotic form of regulated cell death, plays a critical role in the suppression of various tumor types, including ovarian cancer. Artesunate (ART), a derivative of artemisinin, exhibits extensive antitumor effects and is associated with ferroptosis. This study aimed to investigate the mechanisms through which ART induces ferroptosis to inhibit ovarian cancer. Methods RNA sequencing was conducted to identify differentially expressed genes associated with ART-induced ferroptosis. Dual-luciferase reporter assays and electrophoretic mobility shift assays were performed to confirm the interaction between Homeobox C11 (HOXC11) and the Prominin 2 (PROM2) promoter. Cell Counting Kit-8 (CCK-8) assays, flow cytometry, and wound healing assays were used to analyze the antitumor effects of ART. Western blot, biochemical assays and transmission electron microscope were utilized to further characterize ART-induced ferroptosis. In vivo, the effects of ART on ferroptosis were examined using a xenograft mouse model. Results RNA sequencing analysis revealed that the HOXC11, PROM2 and Phosphatidylinositol 3-Kinase/ Protein Kinase B (PI3K/AKT) pathways were downregulated by ART. HOXC11 was found to regulate PROM2 expression by binding to its promoter directly. HOXC11 overexpression reversed ART-induced effects on ovarian cancer cell proliferation, migration, apoptosis and ferroptosis by activating the PROM2/PI3K/AKT signaling axis. Conversely, silencing PROM2 in HOXC11-overexpressing cells restored ART-induced ferroptosis and its associated antitumor effects by inhibiting the PI3K/AKT pathway. Consistently, in vivo studies using a xenograft mouse model confirmed that ART-induced tumor inhibition was mediated by ferroptosis through the suppression of the HOXC11/PROM2/PI3K/AKT pathway. Conclusion This study identifies the HOXC11/PROM2/PI3K/AKT axis as a novel regulatory mechanism underlying ART-induced ferroptosis in ovarian cancer. Targeting the HOXC11/PROM2 axis may represent a promising therapeutic strategy for enhancing ferroptosis, offering new insights for the treatment of ovarian cancer.

Abstract Background Malaria is a mosquito-transmitted disease that kills more than half a million people annually. The lack of effective malaria vaccines and recently increasing malaria cases urge innovative approaches to prevent malaria. Previously, we reported that the extract from the soil-dwelling fungus Purpureocillium lilacinum, a common fungus from the soil, reduced Plasmodium falciparum oocysts in Anopheles gambiae midguts after mosquitoes contacted the treated surface before feeding. Methods We used liquid chromatography to fraction fungal crude extract and tract the active fraction using a contact-wise approach and standard membrane feeding assays. The purified small molecules were analyzed using precise mass spectrometry and tandem mass spectrometry. Results We isolated four active small molecules from P. lilacinum and determined them as leucinostatin A, B, A2, and B2. Pre-exposure of mosquitoes via contact with very low-concentration leucinostatin A significantly reduced the number of oocysts. The half-maximal response or inhibition concentration (EC50) via pre-exposure was 0.7 mg/m2, similar to atovaquone but lower than other known antimalarials. The inhibitory effect of leucinostatin A against P. falciparum during intraerythrocytic development, gametogenesis, sporogonic development, and ookinete formation, with the exception of oocyst development, suggests that leucinostatins play a part during parasite invasion of new cells. Conclusions Leucinostatins, secondary metabolites from P. lilacinum disrupt malaria development, particular transmission to mosquitoes by contact. The contact-wise malaria control as a nonconventional approach is highly needed in malaria-endemic areas. Graphical Abstract

Abstract This paper aims to analyze the risk factors for the recurrence or progression of non-functioning pituitary adenomas (NFPAs) in male patients after transnasal sphenoidal surgery and to develop a predictive model for prognosis. Clinical and follow-up data of 126 male patients with NFPAs treated by transnasal sphenoidal surgery from January 2011 to January 2021 in Fuzhou 900th Hospital were retrospectively analyzed. Lasso regression analysis was used to screen the best predictors, and the predictors were further screened by multivariate logistic regression analysis, and the nomogram prediction model was constructed. The performance of the model was verified by three aspects: discrimination, calibration and clinical utility by using the consistency index (C-index), receiver operating characteristic curve (ROC), calibration curve, clinical decision curve (DCA) and Clinical impact curve (CIC). Out of 126 cases, 7 (5.56%) showed postoperative tumor recurrence, and 18 (14.29%) exhibited postoperative residual regrowth (progression). Age (P = 0.024), maximum tumor diameter (P

Abstract Hypopharyngeal carcinoma is one of the malignant tumors of the head and neck with a particularly poor prognosis. Recurrence and metastasis are important reasons for poor prognosis of hypopharyngeal cancer patients, and malignant proliferation, migration, and invasion of tumor cells are important factors for recurrence and metastasis of hypopharyngeal cancer. Therefore, elucidating hypopharyngeal cancer cells’ proliferation, migration, and invasion mechanism is essential for improving diagnosis, treatment, and prognosis. Plasmacytoma Variant Translocation 1 (PVT1) is considered a potential diagnostic marker and therapeutic target for tumors. However, it remains unclear whether PVT1 is related to the occurrence and development of hypopharyngeal cancer and its specific mechanism. In this study, the promoting effect of PVT1 on the proliferation, migration, and invasion of hypopharyngeal carcinoma FaDu cells was verified by cell biology experiments and animal studies, and it was found that PVT1 inhibited the expression of TGF-β, suggesting that PVT1 may regulate the occurrence and development of hypopharyngeal carcinoma FaDu cells through TGF-β.

Abstract Objective To investigate the clinical efficacy of transumbilical single-incision laparoscopic surgery in the treatment of complicated appendicitis in overweight/obese adolescents. Methods A retrospective analysis was conducted on the clinical data of 226 adolescent patients with complicated appendicitis who were admitted to our hospital from January 2014 to June 2022. Among them, 102 cases underwent transumbilical single-incision laparoscopic appendectomy as the observation group, and another 124 cases underwent conventional three-port laparoscopic appendectomy as the control group. The surgical time, intraoperative blood loss, duration of incisional pain, postoperative flatus time, length of hospital stay, surgical site infection (SSI), satisfaction with cosmetic result, and occurrence of postoperative complications were compared between the two groups. Results Both groups completed the surgery smoothly, and there were no statistically significant differences in gender, age, BMI, duration of illness, white blood cell count, and preoperative CRP value between the two groups (P > 0.05). There were no statistically significant differences in surgical time and intraoperative blood loss between the two groups (P > 0.05). However, the observation group had shorter hospital stays, shorter duration of incisional pain, shorter postoperative time to flatus, and lower overall postoperative complication rates compared to the control group, with statistically significant differences (P

Abstract Background Recombination signal-binding protein for immunoglobulin kappa J region (RBPJ) is a transcriptional regulator that plays an important role in maintaining immune homeostasis. This study aimed to estimate the expression of RBPJ in rheumatoid arthritis (RA) patients and investigate its relationship with RA. Methods A total of 83 newly diagnosed RA patients and 70 healthy controls were included. mRNA was extracted from peripheral blood mononuclear cells (PBMCs), and the expression of RBPJ was detected using quantitative real-time PCR (qRT‒PCR). An RA dataset (GSE89408) was obtained from the Gene Expression Omnibus (GEO) database, and RA synovial tissues were divided into two groups. The differentially expressed genes (DEGs) were selected with the “DESeq2” R package. Results RBPJ expression was lower in RA patients than in health controls and was negatively correlated with the DAS28 score, C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR). RA synovial tissues from GSE89408 were classified into RBPJ-low (≤ 25%) and RBPJ-high (≥ 75%) groups according to RBPJ expression, and 562 DEGs were identified. Gene Ontology (GO) enrichment analyses revealed that the DEGs significantly affected the regulation of T cell activation and lymphocyte/mononuclear cell differentiation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the most enriched pathways of DEGs were the T cell receptor signaling pathway, Th1/2 and Th17 cell differentiation, the PI3K − Akt signaling pathway and cytokine‒cytokine receptor interaction. CytoHubba Plugin revealed that most of the top 10 genes were involved in osteoclast differentiation, the T cell receptor signaling pathway and cytokine‒cytokine receptor interaction. Conclusions RBPJ expression was significantly lower in RA patients and negatively correlated with disease activity. GEO dataset analysis demonstrated that RBPJ may be involved in osteoclast differentiation, T cell activation and differentiation, and the T cell receptor signaling pathway. Our research may contribute to understanding the potential mechanisms by which RBPJ regulates T cell differentiation and cytokine‒cytokine receptor interaction in RA patients.

Abstract Malignant ovarian sex cord-stromal tumors are rare neoplasms that account for approximately 5–7% of all ovarian malignancies, and they are primarily treated with surgery. The prognosis of patients with different surgical extents remains controversial. Therefore, the effects of different surgical extents on the prognosis of patients were explored in this retrospective cohort study. Patients with malignant ovarian sex cord-stromal tumors who underwent surgical treatment from January 2000 to December 2019 were selected. Disease-free survival and overall survival rates were calculated by the Kaplan–Meier method and compared by the log-rank test. Prognosis factors were identified by Cox regression analysis. P

Abstract Background Mushroom poisoning is a significant food safety issue in Guizhou Province, China. Studies on this topic are essential for its prevention and control. We aimed to analyze the epidemiological characteristics of mushroom poisoning and study the correlation between its cases and meteorological factors in Guizhou Province. Methods We collected data on mushroom poisoning and meteorological factors in Guizhou Province in 2023. A descriptive analysis was conducted on the epidemiological features of mushroom poisoning and meteorological factors. We used Spearman correlation analysis and the generalized additive model to examine the relationship between meteorological factors and the number of mushroom poisoning cases. Results In 2023, mushroom poisoning cases in Guizhou Province were concentrated among individuals aged 20–59. Clinical symptoms were primarily gastrointestinal symptoms and occurrences peaked from June to October, mainly in the northeastern region of the province. Most incidents occurred in households. In 72 mushroom poisoning incidents where species were identified, 33 poisonous mushrooms were found. The number of mushroom poisoning cases in Guizhou Province was positively correlated with each meteorological factor(P

In the era of antiretroviral therapy (ART), mortality among people living with the human immunodeficiency virus (HIV) has significantly decreased, yet the population of people living with HIV remains substantial. Among people living with HIV (PLWH), HIV-associated lymphoma (HAL) has surpassed Kaposi’s sarcoma to become the most common tumor in this population in developed countries. However, there remains a dearth of comprehensive and systematic understanding regarding HIV-associated lymphomas. This review aims to shed light on the changes in the immune system among PLWH and the characteristics of the immune microenvironment in HIV-associated lymphoma, with a specific focus on the immune system’s role in these individuals. Additionally, it seeks to explore recent advancements in immunotherapy for the treatment of HIV-associated lymphoma, intending to enhance strategies for immunotherapy in this specific population.

The incidence of prostate, breast, and thyroid cancers has increased in China over the past few decades. Whether and how much these increases can be attributed to overdiagnosis are less understood. This study aimed to estimate the proportion of overdiagnosis among these three cancers in China during 2004–2019. The age-specific cancer incidence, cancer mortality, and all-cause mortality in China were extracted from the Global Burden of Diseases 2019. The lifetime risk of developing and that of dying from each cancer were calculated using the life table method. The proportion of overdiagnosis of a cancer was estimated as the difference between the lifetime risk of developing the cancer and that of suffering from the cancer (including death, metastasis, and symptoms caused by the cancer), further divided by the lifetime risk of developing the cancer. The highest possible values of these parameters were adopted in the estimation so as to obtain the lower bounds of the proportions of overdiagnosis. Sensitivity analyses assuming different lag periods between the diagnosis of a cancer and death from the cancer were performed. The results showed that the lifetime risk of developing prostate, breast, and thyroid cancer increased dramatically from 2004 to 2019 in China, while the increase in the lifetime risk of dying from these cancers was less pronounced. The proportions of overdiagnosis among prostate, breast, and thyroid cancers were estimated to be 7.88%, 18.99%, and 24.92%, respectively, in 2004, and increased to 18.20%, 26.25%, and 29.24%, respectively, in 2019. The increasing trends were statistically significant for all three cancers (all p < 0.001). In sensitivity analyses, the proportions of overdiagnosis decreased, but upward trends over time remained for all three cancers. In conclusion, the overdiagnosis of prostate, breast, and thyroid cancers in China increased from 2004 to 2019, with the highest proportion seen in thyroid cancer and the most rapid increase seen in prostate cancer. Multifaceted efforts by policy makers, guideline developers, and clinicians are needed to tackle this problem.

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.

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.

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.

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

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.

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.

Abstract Pre-trained models based on the Transformer architecture have significantly advanced research within the domain of Natural Language Processing (NLP) due to their superior performance and extensive applicability across multiple technological sectors. Despite these advantages, there is a significant challenge in optimizing these models for more efficient deployment. To be concrete, the existing post-training pruning frameworks of transformer models suffer from inefficiencies in the crucial stage of pruning accuracy recovery, which impacts the overall pruning efficiency. To address this issue, this paper introduces a novel and efficient iteration scheme with conjugate gradient in the pruning recovery stage. By constructing a series of conjugate iterative directions, this approach ensures each optimization step is orthogonal to the previous ones, which effectively reduces redundant explorations of the search space. Consequently, each iteration progresses effectively towards the global optimum, thereby significantly enhancing search efficiency. The conjugate gradient-based faster-pruner reduces the time expenditure of the pruning process while maintaining accuracy, demonstrating a high degree of solution stability and exceptional model acceleration effects. In pruning experiments conducted on the BERTBASE and DistilBERT models, the faster-pruner exhibited outstanding performance on the GLUE benchmark dataset, achieving a reduction of up to 36.27% in pruning time and a speed increase of up to 1.45× on an RTX 3090 GPU.

Background: Skeleton involvement is one of the most significant aspects of Gaucher disease (GD). However, the treatment for spinal involvement in GD among patients undergoing enzyme replacement therapy (ERT) is poorly characterized. We present a case of progressive kyphotic spinal deformity in a young child caused by vertebral involvement, which was managed by posterior spinal fusion without anterior spinal release under ERT. Case presentation: This is a retrospective study. A 10-year-old boy presenting with progression kyphosis (thoracic kyphotic angle of 113°) associated with type-IIIb GD had undergone posterior spinal fusion with segmental pedicle screw fixation (from T6-L3) and Ponte osteotomy. The patient went back to school without further brace protection. Proximal junctional kyphosis (PJK) was observed at 4 months postoperatively. Revision surgery was performed to prevent neurological impairment. Additional posterior spinal fusion from T2–T6 and decompressive laminectomy were performed during the revision surgery. A 2-year follow-up showed no recurrence of PJK and solid fusion was achieved in the patient under ERT and brace protection. Conclusions: Posterior spinal fusion without anterior spinal release is a good treatment option for severe spinal deformity in patients with GD. However, the fusion level and reinforced fixation require careful consideration. Revision surgery and brace protection is needed as long as PJK is observed.

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 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 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 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 Objective The management of length-unstable femoral shaft fractures(LUFSFs) in pediatric patients is still controversial. This study aims to explore the clinical efficacy of ultrasound-guided closed reduction combined with external fixation for treating LUFSFs in children. Methods We conducted a retrospective analysis of clinical data from 19 pediatric patients with LUFSFs who underwent ultrasound-guided closed reduction and external fixation between January 2018 and January 2023. Ultrasound was employed not only to facilitate closed reduction of the fracture but also to guide real-time insertion of Schanz pins and monitor pin length as it traversed the opposite cortex. Surgical time, intraoperative fluoroscopy count, hospital stay length, fracture fixation duration, complication incidence, fracture reduction quality at the final follow-up were recorded. Results The patients’ average age was 7.5 years( range: 5 to 11 years). The mean surgical duration was 70.4 min (range: 48–105 min), and the average intraoperative fluoroscopy count was 6.5 (range: 2–16). Fracture fixation lasted an average of 10.9 weeks (range: 7–20 weeks). All patients were followed up for more than one year. 6 cases of superficial pin tract infection occurred, which resolved with oral antibiotics and enhanced needle tract care. No deep infections were observed. Temporary stiffness of the knee joint was observed in 2 patients. According to Flynn’s efficacy evaluation system, fracture reduction quality at the final follow-up was rated as excellent in 11 cases and satisfactory in 8 cases, yielding a combined success rate of 100% (19/19). Conclusions The technique of ultrasound-guided closed reduction combined with external fixation offers favorable outcomes for children aged 5 to 11 years with LUFSFs, reducing reliance on fluoroscopic guidance.

Abstract Background Epstein-Barr virus (EBV) can be reactivated and proliferated with fatal outcome in immuno-compromised people, but the clinical consequences of EBV infection in patients with severe fever with thrombocytopenia syndrome (SFTS) remain uncertain. In this study, we investigated the infection rate, the influence and the early predictors of EBV infection in SFTS patients. Methods In this retrospective study, SFTS patients who were treated in the First Affiliated Hospital of Nanjing Medical University from May 2011 to August 2021 were enrolled and divided into infected and non-infected groups. We compared the demographic characteristics, clinical manifestations and signs, laboratory tests and prognosis, and explored the risk factors of EBV infection by receiver operating characteristic (ROC) curve and logistic regression. Results A total of 120 hospitalized SFTS patients with EBV-DNA testing were enrolled in this study. Patients with EBV infection had statistically significant higher mortality rate (32.0% vs. 11.43%, P = 0.005). Compared with the non-infected group, the EBV-infected group had higher levels of C-reactive protein (CRP), creatine-kinase (CK), fasting blood glucose (FBG), blood urea nitrogen (BUN), D-dimer, and CD56+ cell counts, lower levels of immunoglobulin G (IgG), IgM, complement 3 (C3), and C4. The proportion of patients with age ≥ 60 years and ferritin > 1500.0 ng/ml in the EBV-infected group was significantly higher than that in the non-infected group. The results of ROC analysis showed that the cut-off values of CRP, IgG, C3, C4, and CD56+ cell counts to predict EBV infection were 13.2 mg/l, 12.5 g/l, 1.1 g/l, 0.6 g/l, 0.3 g/l, and 94.0 cells/µl. Multivariable logistic analysis showed that age ≥ 60 years old, CRP > 13.2 mg/l, BUN > 5.4 mmol/l, ferritin > 1500.0 ng/ml, IgG 94.0 cells/µl were the independent risk factors of EBV infection in SFTS patients. Conclusions SFTS combined with EBV infection is associated with high morbidity and mortality. It is necessary to strengthen screening for EBV infection and its early predictive markers after admission in SFTS patients.

Abstract EGFR mutations are critical oncogenic drivers in lung adenocarcinoma (LUAD). However, the mechanisms by which they impact the tumor microenvironment (TME) and tumor immunity are unclear. Furthermore, the reasons underlying the poor response of EGFR-mutant (EGFR-MU) LUADs to immunotherapy with PD-1/PD-L1 inhibitors are unknown. Utilizing single-cell RNA (sc-RNA) and bulk RNA sequencing datasets, we conducted high-dimensional weighted gene coexpression network analysis to identify key genes and immune-related pathways contributing to the immunosuppressive TME. EGFR-MU cancer cells downregulated MHC class I genes to evade CD8+ cytotoxic T cells, expressed substantial levels of MHC class II molecules, and engaged with CD4+ regulatory T cells (Tregs). EGFR-MU tumors may recruit Tregs primarily through the CCL17/CCL22/CCR4 axis, leading to a Treg-enriched TME. High levels of MHC class II-positive cancer-associated fibroblasts and tumor endothelial cells were found within EGFR-MU tumors. Owing to the absence of costimulatory factors, they may inhibit rather than activate the tumor antigen-specific CD4+ T-cell response, contributing further to immune suppression. Multiplex immunohistochemistry analyses in a LUAD cohort confirmed increased expression of MHC class II molecules in cancer cells and fibroblasts in EGFR-MU tumors. Our research elucidates the highly immunosuppressive TME in EGFR-MU LUAD and suggests potential targets for effective immunotherapy.

Abstract Objective To investigate the relationship between uric acid to high-density lipoprotein cholesterol ratio (UHR) and circulating α-klotho levels in U.S. adults. Methods A cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2016. Circulating α-klotho was defined as the dependent variable and UHR was defined as the independent variable. Multivariable linear regression was performed to assess the relationship between the independent and dependent variables. The nonlinear relationship and effect size between UHR and α-klotho were evaluated using smooth curve fitting and threshold effect analysis. Subgroup analysis and sensitivity analysis were conducted to determine the stability of the results. The diagnostic performance of UHR and α-klotho in common elderly diseases was compared using ROC (Receiver Operating Characteristic) analysis. Results Among 12,849 participants, there was a negative relationship between the UHR and circulating α-klotho. In the fully adjusted overall model, each unit increase in UHR was associated with a decrease of 4.1 pg/mL in α-klotho. The threshold effect analysis showed that before the inflection point of 8.2, each unit increase in UHR was associated with a decrease of 15.0 pg/mL in α-klotho; beyond the inflection point of 8.2, each unit increase in UHR was associated with a decrease of 2.8 pg/mL in α-klotho. Subgroup analyses and sensitivity analysis indicated that the relationship between UHR and α-klotho remained stable across most populations. The ROC diagnostic test indicated that the evaluative efficacy of UHR in diagnosing age-related diseases was comparable to that of α-klotho. Conclusion This study revealed that the UHR was associated with the circulating α-klotho concentration, with a negative association observed in most cases. This finding suggested that the UHR might be a promising indicator for evaluating circulating α-klotho levels.

Abstract The increasing prevalence of myopia worldwide presents a significant public health challenge. A key strategy to combat myopia is with early detection and prediction in children as such examination allows for effective intervention using readily accessible imaging technique. To this end, we introduced DeepMyopia, an artificial intelligence (AI)-enabled decision support system to detect and predict myopia onset and facilitate targeted interventions for children at risk using routine retinal fundus images. Based on deep learning architecture, DeepMyopia had been trained and internally validated on a large cohort of retinal fundus images (n = 1,638,315) and then externally tested on datasets from seven sites in China (n = 22,060). Our results demonstrated robustness of DeepMyopia, with AUCs of 0.908, 0.813, and 0.810 for 1-, 2-, and 3-year myopia onset prediction with the internal test set, and AUCs of 0.796, 0.808, and 0.767 with the external test set. DeepMyopia also effectively stratified children into low- and high-risk groups (p