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Objective·To develope an auditory brainstem implant (ABI) vocoder based on cochlear implant (CI) vocoder characteristics and ABI electrode array topology, and to verify its reliability.Methods·An "n-of-m" coding strategy CI/ABI vocoder was constructed based on MATLAB. Within each frame, only the envelopes of the n channels with the highest energy were selected. The interaction coefficient (IC) (range: 1‒3), channel numbers (range: 5‒22), and electrode array topology (CI/ABI) were adjustable parameters, allowing for the synthesis of simulated speech. Psychoacoustic evaluation was employed, recruiting normal hearing subjects to perform closed-set simulated phoneme perception. The phoneme recognition accuracy (20 vowel questions/condition, 11 consonant questions/condition) was compared with the corresponding conditions of CI and ABI from reference literature to determine the IC value of the vocoder and verify its reliability.Results·The vocoder successfully synthesized all test stimuli. In the closed-set CI-simulated speech recognition, the simulated vowel and consonant recognition accuracy for IC2 and IC3 conditions showed no significant difference compared to the accuracy reported in the CI reference literature (P>0.05). The difference in vowel and consonant accuracy between IC2 and the literature was smaller than that between IC3 and the literature (vowel |d|=1.6% vs. 20%, consonant |d|=8.4% vs. 9.9%), thus determining the optimal interaction coefficient of this model as 2. Subsequently, when modifying the electrode array topology to ABI, it was found that the simulated phoneme recognition accuracy for a 16-channel ABI was significantly lower than that for the 16-channel CI group, consistent with the reported literature. The simulated vowel and consonant accuracy within the 5‒8 channel range for ABI showed no significant difference (P>0.05), also aligning with the trend reported in the literature.Conclusion·A CI/ABI vocoder based on "n-of-m" coding strategy is established and the optimal IC is determined. The established ABI encoder has been evaluated for high reliability through psychoacoustic experiments. It provides suitable technical means for validating ABI-specific coding strategies.

Abstract This study investigated the integration of online learning into complete denture rehabilitation (CDR) training for dental interns, highlighting its impact on their education and readiness for clinical practice. Given that CDR poses significant challenges due to its technical complexity and profound influence on patient well-being, online learning has emerged as a strategic educational tool to enhance interns’ knowledge and skills. This research included the administration of a comprehensive questionnaire to 63 dental interns to assess their backgrounds, experiences with online learning, and attitudes toward its application in CDR education. The results revealed strong engagement with online learning, with a majority valuing its flexibility, accessibility, and capacity to facilitate self-paced, individualized learning. Despite the enthusiasm for online modalities, the results identified notable gaps in interns’ confidence in and preparedness for performing CDR, highlighting the need for targeted improvements in online curriculum development. By emphasizing the essential role of innovative teaching methods, including virtual reality (VR), this study underscores the need for a balanced educational approach that combines traditional and digital platforms. This strategy aims to prepare future dental professionals for the complexities of modern clinical environments, ensuring that they are well equipped to meet the diverse needs of the edentulous population.

Abstract Long-chain fatty acid transport protein 1 (FATP1) is a member of the fatty acid transporter family. It facilitates transmembrane transport of fatty acids and participates in lipid metabolism. Lipids are essential components of the cell and organelle membranes of Trichinella spiralis. The nematode has lost the capacity to synthesise the necessary lipids de novo and has instead evolved to obtain fatty acids and their derivatives from its host. This study aims to ascertain the primary biological characteristics and roles of T. spiralis FATP1 (TsFATP1) in lipid metabolism, larval moulting, and the development of this nematode. The results show that TsFATP1 is highly expressed at enteral T. spiralis stages, mainly localised at the cuticle, the stichosome and the intrauterine embryos of the parasite. The silencing of the TsFATP1 gene by TsFATP1-specific dsRNA significantly decreases the expression levels of TsFATP1 in the worm. It reduces the contents of ATP, triglycerides, total cholesterol, and phospholipids both in vitro and in vivo. RNAi inhibits lipid metabolism, moulting, and the growth of this nematode. The results demonstrate that TsFATP1 plays an essential role in lipid metabolism, moulting, and the development of T. spiralis. It could also be a target candidate for the anti-Trichinella vaccine and drugs.

Abstract The sense of agency refers to the feeling of initiating and controlling one’s actions and their resulting effects on the external environment. Previous studies have uncovered behavioral evidence of excessive self-attribution and, conversely, a reduction in the sense of agency in patients with schizophrenia. We hypothesize that this apparent paradox is likely to result from impairment in lower-level processes underlying the sense of agency, combined with a higher-level compensational bias. The present study employed three behavioral tasks utilizing the same stimuli and experimental design to systematically evaluate multiple factors that influence the sense of agency, including motor control, sensorimotor processing, and self-attribution. Participants’ real-time mouse movements were combined with prerecorded motions of others in ratios of 30/70, 55/45, or 80/20, with an additional angular bias of either 0° or 90°. Twenty-six patients with schizophrenia and 27 health control volunteers participated in the three tasks. Patients with schizophrenia performed significantly worse in the reaching and control detection tasks than healthy controls. However, their self-attribution in the control judgment task was comparable to that of the healthy controls. Patients with schizophrenia were impaired in motor control components and in the detection of control using sensorimotor information, but their evaluation of agency remained relatively less affected. This underscores the importance of distinguishing between different subcomponents when addressing the abnormal sense of agency in patients with schizophrenia. Subsequent cluster analysis revealed that the combined task performance accurately distinguished between the patients and healthy control participants.

Objective The microbial dolomite of the second Member of the Dengying Formation（Deng 2 Member） in the Penglai area of the Sichuan Basin is widely distributed and considered a potential target for deep carbonate oil and gas exploration. Unlike conventional high-quality reservoirs characterized by porosity and karst fractures, the carbonate rocks of the Deng 2 Member mainly consist of microbial dolomite. The genesis and diagenetic evolution of these high-quality reservoirs remain unclear. Methods This study employed petrographic thin sections, scanning electron microscopy (SEM), cathodoluminescence, and computed tomography （CT）scanning to conduct a detailed analysis of the microbial dolomite reservoirs in the Dengying Formation, using field outcrop and core samples. The aim was to gain a deeper understanding of the effects of diagenesis on pore formation and the development of high-quality reservoirs. Results and Conclusion The microbial carbonate reservoirs in the study area were characterized by low porosity and very low permeability, predominantly consisting of fracture-porosity (cavity) type microbial dolomite. The reservoir space was primarily composed of intergranular dissolution pores, residual framework dissolution pores, intragranular dissolution pores, and small to medium-sized dissolution cavities, with minor occurrences of intercrystalline pores and intercrystalline dissolution pores. The Deng 2 Member has undergone multiple diagenetic processes; penecontemporaneous dissolution and early epigenetic dissolution were key factors in enhancing porosity. Significance These findings enhance the understanding of the genesis of high-quality microbial carbonate reservoirs in the Ediacaran System of the Sichuan Basin and provide valuable information for deep oil and gas exploration and development in the region.

Abstract The face serves as a crucial cue for self-identification, while the sense of agency plays a significant role in determining our influence through actions in the environment. The current study investigates how self-identification through facial recognition may influence the perception of control via motion. We propose that self-identification might engender a belief in having control over one’s own face, leading to a more acute detection and greater emphasis on discrepancies between their actions and the sensory feedback in control judgments. We refer to the condition governed by the belief in having control as the exploitation mode. Conversely, when manipulating another individual’s face, the belief in personal control is absent. In such cases, individuals are likely to rely on the regularity between actions and sensory input for control judgments, exhibiting behaviors that are exploratory in nature to glean such information. This condition is termed the explorative mode. The study utilized a face-motion mixing paradigm, employing a deep generative model to enable participants to interact with either their own or another person’s face through facial and head movements. During the experiment, participants observed either their own face or someone else’s face (self-face vs. other-face) on the screen. The motion of the face was driven either purely by their own facial and head motion or by an average of the participant’s and the experimenter’s motion (full control vs. partial control). The results showed that participants reported a higher sense of agency over the other-face than the self-face, while their self-identification rating was significantly higher for the self-face. More importantly, controlling someone else’s face resulted in more movement diversity than controlling one’s own face. These findings support our exploration–exploitation theory: When participants had a strong belief in control triggered by the self-face, they became highly sensitive to any sensorimotor prediction errors, leading to a lower sense of agency. In contrast, when the belief of control was absent, the exploration mode triggered more explorative behaviors, allowing participants to efficiently gather information to establish a sense of agency.

How to capture the dynamic changes and dependencies of user behavior is a vital issue existing in point-of-interest (POI) recommendation. It mainly faces challenges including data scarcity, difficulty in extracting spatio-temporal sequence features and in capturing users?? individuated differences. In order to address these challenges, this paper proposes a time-sequence POI recommendation method based on spatio-temporal vicinity perception and implicit changes of users?? state. This method is aimed at converting the learning of user behavior into the learning of users?? latent state, combined with distance information to introduce spatial information, which effectively captures users?? mobile characteristics. Firstly, the variational autoencoder is utilized to represent the potential state of users. And then the dependency among the latent states is learnt through the graph neural network so as to capture the time-sequence dependence of user behavior. Furthermore, this paper makes use of the attention mechanism and radial basis function to capture the spatial dependence between the user and location candidate sets. Next, this paper evaluates the frequencies of user visiting each location, hence achieving point-of-interest recommendation. Experimental comparison and analysis on three real datasets demonstrate that the temporal recommendation performance of the proposed method is superior to existing benchmark algorithms.

Abstract Benzodiazepines, commonly used for anxiolytics, hinder conditioned fear extinction, and the underlying circuit mechanisms are unclear. Utilizing remimazolam, an ultra-short-acting benzodiazepine, here we reveal its impact on the thalamic nucleus reuniens (RE) and interconnected hippocamposeptal circuits during fear extinction. Systemic or RE-specific administration of remimazolam impedes fear extinction by reducing RE activation through A type GABA receptors. Remimazolam enhances long-range GABAergic inhibition from lateral septum (LS) to RE, underlying the compromised fear extinction. RE projects to ventral hippocampus (vHPC), which in turn sends projections characterized by feed-forward inhibition to the GABAergic neurons of the LS. This is coupled with long-range GABAergic projections from the LS to RE, collectively constituting an overall positive feedback circuit construct that promotes fear extinction. RE-specific remimazolam negates the facilitation of fear extinction by disrupting this circuit. Thus, remimazolam in RE disrupts fear extinction caused by hippocamposeptal intermediation, offering mechanistic insights for the dilemma of combining anxiolytics with extinction-based exposure therapy.

BackgroundAtrial fibrillation (AF) is a prevalent cardiac arrhythmia associated with substantial morbidity and mortality. Oxidative stress (OS) has been implicated in the pathogenesis of AF, suggesting that targeting OS-related genes could offer novel therapeutic opportunities. This study aimed to identify causal OS-related genes contributing to AF through a comprehensive multi-omics Summary-based Mendelian Randomization (SMR) approach.MethodsThis study integrated data from genome-wide association studies (GWAS) with methylation quantitative trait loci (mQTL), expression QTL (eQTL), and protein QTL (pQTL) to explore the relationships between oxidative stress-related (OS-related) genes and AF risk. Genes associated with oxidative stress and AF were obtained from the Nielsen et al. study (discovery) and the FinnGen study (replication). The SMR analysis and HEIDI test were utilized to assess causal associations, followed by Bayesian co-localization analysis (PPH4 > 0.5) to confirm shared causal variants. Multi-omics data were employed to analyze the associations within mQTL-eQTL pathways. A two-sample MR analysis was conducted for sensitivity verification. The significance of findings was determined using a false discovery rate (FDR) < 0.05 and p_HEIDI > 0.01.ResultsAt the DNA methylation level, 19 CpG sites near 7 unique genes were found to have causal effects on AF and strong co-localization evidence support (PPH4 > 0.70). At the gene expression level, six oxidative stress-related genes from eQTLGen and three from GTEx (v8), including TNFSF10, CDKN1A, ALOX15, TTN, PTK2, ALB, KCNJ5, and CASQ2, were found to have causal effects on AF in the sensitivity and co-localization analyses (PPH4 > 0.50). At the circulating protein level, both ALAD (OR 0.898, 95% CI 0.845–0.954, PPH4 = 0.67) and APOH (OR 0.896, 95% CI 0.844–0.952, PPH4 = 0.93) were associated with a lower risk of AF, and APOH was validated in the replication group. After integrating the multi-omics data between mQTL and eQTL, we identified two oxidative stress-related genes, TTN and CASQ2. The methylation of cg09915519 and cg10087519 in TTN was associated with higher expression of TTN and a lower risk of AF, which aligns with the negative effect of TTN gene expression on AF risk. TTN may play a protective role in AF.ConclusionThis study identified several OS-related genes, particularly TTN, as having causal roles in AF, which were verified across three-omics pathways. The findings underscore the importance of these genes in AF pathogenesis and highlight their potential as therapeutic targets. The integration of multi-omics data provides a comprehensive understanding of the molecular mechanisms underlying AF, paving the way for targeted therapeutic strategies.

Abstract Background Growth hormone (GH) has been proposed as an adjunct in in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles, especially in women with poor ovarian response. However, it is unclear whether GH supplementation is effective in women with poor embryonic development in the previous IVF cycle. The aim of this study was to evaluate the effectiveness of GH supplementation in IVF/ICSI cycles in women with poor embryonic development in the previous cycle. Methods This is a retrospective cohort study from a public fertility center in China, in which we performed propensity score-matching (PSM) for female age and AFC in a ratio of 1:1. We compared the cumulative live birth rate per started cycle, as well as a series of secondary outcomes. We included 3,043 women with poor embryonic development in the previous IVF/ICSI cycle, of which 1,326 had GH as adjuvant therapy and 1,717 had not. After PSM, there were 694 women in each group. Results After PSM, multivariate analyses showed the cumulative live birth rate to be significantly higher in the GH group than the control group [N = 694, 34.7% vs. N = 694, 27.5%, risk ratio (RR): 1.4 (95%CI: 1.1–1.8)]. Endometrial thickness, number of oocytes retrieved, number of embryos available, and number of good-quality embryos were significantly higher in the GH group compared to controls. Pregnancy outcomes in terms of birth weight, gestational age, fetal sex, preterm birth rate, and type of delivery were comparable. When we evaluated the impact of GH on different categories of female age, the observed benefit in the GH group did not appear to be significant. When we assessed the effect of GH in different AFC categories, the effect of GH was strongest in women with an AFC5-6 (32.2% versus 19.5%; RR 2.0; 95% CI 1.2–3.3). Conclusions Women with poor embryonic quality in the previous IVF/ICSI cycles have higher rates of cumulative live birth with GH supplementation.

Objective To investigate the high risk factors of endometrial polyps (EPs) in infertile patients and its impact on the pregnancy outcome after embryo transfer. Methods A case-control trail was conducted on the infertility patients who undergoing embryo transfer in our hospital for the first time after hysteroscopy from January 2016 to December 2022.Their clinical data were collected and retrospectively analyzed.Univariate and stepwise logistic regression analyses were used to identify the risk factors for EPs, and the impact of polyps on the pregnancy outcomes of assisted reproductive pregnancy was analyzed with propensity score matching (PSM) at a 1:2 ratio. Results A total of 388 patients diagnosed with EPs and undergoing hysteroscopic endometrial polypectomy were assigned into the EPs group, and 2 163 non-polyp patients were into the non-EPs group.Univariate analysis showed statistical differences were observed in age[31(29, 34)vs 31(28, 33), P=0.002], history of pelvic inflammatory disease (42.78%vs 64.17%, P=0.000), age at menarche[14(12, 14)vs 13(12, 14) years old, P=0.000], number of pregnancies[0(0, 1)vs 1(0, 2), P=0.000], primary infertility (60.30%vs 50.20%, P=0.000), duration of infertility[4(2.1, 6.0)vs 4(2.0, 6.0) years, P=0.002], concomitant endometriosis (9.53%vs 6.52%, P=0.032), concomitant uterine fibroids (11.85%vs 6.93%, P=0.001), and basal estrogen level[38.12(27.00, 59.00)vs 36.00(25.00, 53.00)μg/L, P=0.016]between the 2 groups.Logistic stepwise regression analysis indicated that age (OR=1.082, 95%CI: 1.053~1.113, P < 0.05), primary infertility (OR=2.951, 95%CI: 1.990~4.376, P < 0.05), and elevated basal estrogen (OR=1.003, 95%CI: 1.001~1.005, P < 0.05) were risk factors for EPs.The postoperative biochemical pregnancy rate (59.28%vs 52.70%), clinical pregnancy rate (53.09%vs 45.48%), and live birth rate (43.81%vs 35.82%) were significantly higher in the matched EPs group than the non-EPs group (P < 0.05).No statistical difference was observed in pregnancy outcome in the patients with different polyp locations and sizes.The patients with multiple polyps had an obvious higher rate of early miscarriage than those with single polyp (17.27%vs 7.29%, P < 0.05), while those with recurrent polyps also had a higher rate of early miscarriage than those with primary polyps (27.78%vs 11.23%, P < 0.05). Conclusion Age, primary infertility, and elevated basal estrogen are risk factors for EPs in infertility patients, while hysteroscopic endometrial polypectomy prior to embryo transfer results in improved pregnancy outcomes in those with EPs.The location and size of endometrial polyps have weak impact on pregnancy outcomes following embryo transfer, but, the presence of multiple or recurrent polyps may elevate the risk of early miscarriage.

Abstract Osteoporosis is usually caused by excessive bone resorption and energy metabolism plays a critical role in the development of osteoporosis. However, little is known about the role of energy metabolism-related genes in osteoporosis. This study aimed to explore the important energy metabolism-related genes involved in the development of osteoporosis and develop a diagnosis signature for osteoporosis. The GSE56814, GSE62402, and GSE7158 datasets were downloaded from the NCBI Gene Expression Omnibus. The intersection of differentially expressed genes between high and low levels of body mineral density (BMD) and genes related to energy metabolism were screened as differentially expressed energy metabolism genes (DE-EMGs). Subsequently, a DE-EMG-based diagnostic model was constructed and differential expression of genes in the model was validated by RT-qPCR. Furthermore, a receiver operating characteristic curve and nomogram model were constructed to evaluate the predictive ability of the diagnostic model. Finally, the immune cell types in the merged samples and networks associated with the selected optimal DE-EMGs were constructed. A total of 72 overlapped genes were selected as DE-EMGs, and a five DE-EMG based diagnostic model consisting B4GALT4, ADH4, ACAD11, B4GALT2, and PPP1R3C was established. The areas under the curve of the five genes in the merged training dataset and B4GALT2 in the validation dataset were 0.784 and 0.790, respectively. Moreover, good prognostic prediction ability was observed using the nomogram model (C index = 0.9201; P = 5.507e−14). Significant differences were observed in five immune cell types between the high- and low-BMD groups. These included central memory, effector memory, and activated CD8 T cells, as well as regulatory T cells and activated B cells. A network related to DE-EMGs was constructed, including hsa-miR-23b-3p, DANCR, 17 small-molecule drugs, and two Kyoto Encyclopedia of Genes and Genomes pathways, including metabolic pathways and pyruvate metabolism. Our findings highlighted the important roles of DE-EMGs in the development of osteoporosis. Furthermore, the DANCR/hsa-miR-23b-3p/B4GALT4 axis might provide novel molecular insights into the process of osteoporosis development.

Background: Coronary heart disease (CHD) is a common heart disease and a leading cause of death in developed countries and some developing countries such as China. It is recognized as a multifactorial disease, with dyslipidemia being closely associated with the progression of coronary atherosclerosis. Numerous studies have confirmed the relationship between a single indicator of low-density lipoprotein cholesterol (LDL-C) or high-density lipoprotein cholesterol (HDL-C) and CHD. However, the association between LDL-C to HDL-C ratio (LHR) and CHD remains unclear. This study aimed to comprehensively explore the association between LHR and CHD. Methods: This meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses. PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases were comprehensively searched up to June 15, 2023, to find the studies that indicated the connection between LHR and CHD. A total of 12 published studies were selected. The random-effects model was used to pool the data and mean difference (MD), and the 95% confidence intervals (CI) were taken as the overall outcome. No language restrictions existed in the study selection. The Review Manager 5.4 and Stata 12 were used to analyze the data. Results: Twelve high-quality clinical studies involving 5544 participants, including 3009 patients with CHD, were enrolled in the meta-analysis. The findings revealed that the LHR was higher by 0.65 in patients with CHD than in those without CHD (MD, 0.65; 95% CI, 0.50–0.80). Conclusion: The LHR was found to be positively correlated with CHD, suggesting that it may serve as a potential indicator of CHD.

The dynamics of hydrological processes and the storage mechanisms of karst water resources are the most important issues in karst hydrology. The impact of environmental changes on water quantity, and the evaluation and quantification of eco-hydrological processes remain poorly addressed. In this study, high-frequency continuous monitoring in multi-scale karst watersheds in Southwest China combined the approaches of water isotopes and the hybrid single-particle lagrangian integrated trajectory (HYSPLIT) model to identify the recharge mechanisms between atmospheric vapor, rainfall, surface water, and groundwater, and to reveal the interaction of eco-hydrological processes. The dominant moisture sources in Puding (PD) County were the Indian Ocean (43–69%) and local moisture (24–33%). The δ18O and deuterium excess (d-excess) values showed a positive correlation indicating that secondary or sub-cloud evaporation was prominent in the wet seasons. Karst water line-conditioned excess (lc-excess) indicated that karst water interacted with recent precipitation, groundwater, and evaporation across seasons. Owing to its specific hydrogeological structure, surface water and rainwater have a higher contribution rate to groundwater replenishment. The Chenqi stream replenished the Houzhai River mainly in the form of groundwater, with percentages ranging from 38.1 to 93.5% in the wet season, and 47.8–80.1% in the dry season. In the Houzhai outlet, surface water and groundwater interconverted frequently with a percentage of 45.6–49.1%. We believe this is the first systematic study to quantify the supply relationship between water vapor transport, rainfall, surface water and groundwater in the Chinese karst zone, making a significant move forward in the field of karst hydrological processes and improving the efficiency of water resource evaluation and management.

Background This study aims to establish a simplified and effective animal model of catheter malfunction caused by omental wrapped using negative pressure suction.Method The peritoneal dialysis catheter outlet was linked to a negative-pressure (0-75mmHg) suction pump to intensify the negative pressure. Different negative pressures were tested for model construction in vitro. In vivo, a model of peritoneal catheter malfunction caused by omental wrapped was constructed in five beagles after catheter placement. Catheter drainage conditions and related complications were monitored before and after the model establishment.Results In the vitro experiment, the overall success rate of constructed models was 90% (36/40). The total malfunction rate was higher in 62.5 mmHg (10/10) and 75 mmHg (10/10) than in 12.5 mmHg (8/10) and 37.5 mmHg (8/10). The outflow velocity of dialysate at 62.5 mmHg was significantly lower than that at 12.5 mmHg and 37.5 mmHg, without a statistically significant difference compared to 75 mmHg. In the in vivo experiment, catheter outflow velocity increased, and residual fluid volume decreased after omental wrapped (99.6 ± 6.7 ml/min vs. 32.6 ± 4.6 ml/min at initial five minutes, p

IntroductionIn the realm of natural frozen-thawed embryo transfer (FET) cycles, the application of luteal phase support (LPS) is a prevalent practice, primarily due to its beneficial impact on reproductive outcomes. Among the various LPS medications, human chorionic gonadotropin (hCG) is one that exerts its function on both the corpus luteum and the endometrium.ObjectiveTo evaluate the effect of hCG administration as LPS on reproductive outcomes in natural FET cycles.MethodsThis study was a retrospective cohort analysis conducted at a tertiary care hospital. It included women who underwent natural FET treatment from January 2018 to December 2022. Participants were divided into the hCG LPS group and the non-hCG LPS group on the basis of whether they used hCG as LPS after blastocyst transfer. The primary outcome was the clinical pregnancy and live birth rates. The secondary outcomes included the early miscarriage rate (before 12th gestational week) and total miscarriage rate.ResultsA total of 4762 women were included in the analysis, and 1910 received hCG LPS and 2852 received no hCG LPS (control group). In the general cohort, the clinical pregnancy and live birth rates in the hCG LPS group were significantly lower than those in the control group (63.82% vs 66.41%, aOR 0.872, 95% CI 0.765–0.996, P=0.046; 53.98% vs 57.15%, aOR 0.873, 95% CI 0.766–0.991, P=0.035, respectively). The early miscarriage and total miscarriage rates were similar between the two groups. In a subgroup analysis, in women who received an hCG trigger, there was no significant difference in the clinical pregnancy rate or live birth rate between the two groups. However, in women who ovulated spontaneously, the clinical pregnancy and live birth rates in the hCG LPS group were significantly lower than those in the control group (60.99% vs 67.21%, aOR 0.786, 95% CI 0.652–0.946, P=0.011; 50.56% vs 57.63%, aOR 0.743, 95% CI 0.619–0.878, P=0.001, respectively).ConclusionAmong women undergoing natural cycle frozen–thawed blastocyst transfer, hCG LPS is associated with lower clinical pregnancy and live birth rates. Additionally, the adverse effect of hCG LPS is more pronounced in women who ovulate spontaneously.

Background Colorectal cancer (CRC) remains a global health concern with persistently high incidence and mortality rates. However, the specific pathogenesis of CRC remains poorly understood. This study aims to investigate the role and pathogenesis of serine and arginine rich splicing factor 10 (SRSF10) in colorectal cancer. Methods Bioinformatics analysis was employed to predict SRSF10 gene expression in CRC patients. Functional experiments involving SRSF10 knockdown and overexpression were conducted using CCK8, transwell, scratch assay, and flow cytometry. Additionally, the PRIdictor website was utilized to predict the SRSF10 interaction site with RFC5. The identification of different transcripts of SRSF10-acting RFC5 pre-mRNA was achieved through agarose gel electrophoresis. Result The knockdown of SRSF10 inhibited the proliferation and migration ability of CRC cells, while promoting apoptosis and altering the DNA replication of CRC cells. Conversely, when SRSF10 was highly expressed, it enhanced the proliferation and migration ability of CRC cells and caused changes in the cell cycle of colorectal cancer cells. This study revealed a change in the replicating factor C subunit 5 (RFC5) gene in colorectal cancer cells following SRSF10 knockdown. Furthermore, it was confirmed that SRSF10 increased RFC5 exon2-AS1(S) transcription variants, thereby promoting the development of colorectal cancer through AS1 exclusion to exon 2 of RFC5. Conclusion In summary, this study demonstrates that SRSF10 promotes the progression of colorectal cancer by generating an aberrantly spliced exclusion isoform of AS1 within RFC5 exon 2. These findings suggest that SRSF10 could serve as a crucial target for the clinical diagnosis and treatment of CRC.

Excessive alcohol exposure can cause neurobehavioral deficits and structural alterations in the brain. Emerging research evidence suggests that endoplasmic reticulum (ER) stress plays an important role in alcohol-induced neurotoxicity. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an ER stress inducible protein and is responsible to maintain ER homeostasis. MANF is highly expressed in both the developing and mature brain. We have previously shown that MANF deficiency exacerbated alcohol induced neurodegeneration and ER stress in the developing brain. However, little is known regarding the role of MANF in alcohol induced neuronal damage in the adult brain. In this study, we used a neuron-specific MANF knockout (KO) mouse model to investigate the effect of MANF deficiency on acute binge alcohol exposure-induced neurobehavioral deficits and ER stress. Adult male and female MANF KO mice and littermate controls received daily alcohol gavage (5 g/kg) for 10 days and then subjected to a battery of neurobehavioral tests including rotarods, balance beam, DigiGait, open field, elevated plus maze, Barnes maze, and three-chamber sociability task. Female MANF KO animals were more susceptible to alcohol-induced body weight loss. Alcohol exposure did not affect motor function, however female but not male MANF KO mice exhibited an increased locomotor activity in open field test. Learning and memory was not significantly impaired, but it was altered by MANF deficiency in females while it was affected by alcohol treatment in males. Both alcohol-exposed male and female MANF KO mice displayed increased sociability. Alcohol induced the expression of ER chaperones GRP78 and GRP94 and altered the levels of several unfolded protein response (UPR) and neuroinflammation markers in MANF KO mice in a sex-specific manner. The expression of MANF interacting proteins neuroplastin, PDIA1, and PDIA6 was increased in MANF KO mice, and was further induced by alcohol. In conclusion, alcohol exposure and neuronal MANF deficiency interacted to alter neurobehavioral outcomes, ER homeostasis and neuroinflammation in a sex-specific manner.

BackgroundIn recent years, with the rapid advancement of fundamental ultrasonography research, the application of ultrasound in disease treatment has progressively increased. An increasing body of research indicates that microbubbles serve not only as contrast agents but also in conjunction with ultrasound, enhancing cavitation effects and facilitating targeted drug delivery, thereby augmenting therapeutic efficacy. The objective of this study is to explore the current status and prevailing research trends in this field from 2009 to 2023 through bibliometric analysis and to forecast future developmental trajectories.MethodsWe selected the Science Citation Index Expanded (SCI-Expanded) from the Web of Science Core Collection (WOSCC) as our primary data source. On 19 January 2024, we conducted a comprehensive search encompassing all articles and reviews published between 2009 and 2023 and utilized the bibliometric online analysis platform, CiteSpace and VOSviewer software to analyze countries/regions, institutions, authors, keywords, and references, used Microsoft Excel 2021 to visualize the trends of the number of articles published by year.ResultsBetween 1 January 2009, and 31 December 2023, 3,326 publications on ultrasound combined with microbubble therapy technology were included. There were a total of 2,846 articles (85.6%) and 480 reviews (14.4%) from 13,062 scholars in 68 countries/regions published in 782 journals. China and the United States emerged as the primary contributors in this domain. In terms of publication output and global institutional collaboration, the University of Toronto in Canada has made the most significant contribution to this field. Professor Kullervo Hynynen has achieved remarkable accomplishments in this area. Ultrasound in Medicine and Biology is at the core of the publishing of research on ultrasound combined with microbubble therapy technology. Keywords such as “sonodynamic therapy,” “oxygen,” “loaded microbubbles” and “Alzheimer’s disease” indicate emerging trends in the field and hold the potential to evolve into significant areas of future investigation.ConclusionThis study provides a summary of the key contributions of ultrasound combined with microbubble therapy to the field’s development over the past 15 years and delves into the historical underpinnings and contemporary trends of ultrasound combined with microbubble therapy technology, providing valuable guidance for researchers.

BackgroundCongenital scoliosis and congenital anomalies of the kidney and urinary tract are distinct genetic disorders with differing clinical manifestations. Clinically, their coexistence is not rare, but the etiologies of these complex diseases remain largely unknown, especially their shared genetic basis.MethodsWe sequenced the genomes of 40 individuals diagnosed with both CS and CAKUT, alongside 2,764 controls from a Chinese Han population cohort. Our analyses encompassed gene-based and pathway-based weighted rare variant association tests, complemented by copy number variant association analyses, aiming to unravel the shared genomic etiology underlying these congenital conditions.ResultsGene-based analysis identified PTPN11 as a pivotal gene influencing both skeletal and urinary system development (P = 1.95E-21), participating in metabolic pathways, especially the MAPK/ERK pathway known to regulate skeletal and urinary system development. Pathway-based enrichment showed a significant signal in the MAPK/ERK pathway (P = 3E-04), reinforcing the potential role of PTPN11 and MAPK/ERK pathway in both conditions. Additionally, CNV analysis pinpointed IGFLR1 haploinsufficiency as a potential influential factor in the combined CS-CAKUT phenotypic spectrum.ConclusionThis study enriches our understanding of the intricate genomic interplay underlying congenital scoliosis and kidney and urinary tract anomalies, emphasizing the shared genetic foundations between these two disorders.

Abstract Congenital vertebral malformation, affecting 0.13–0.50 per 1000 live births, has an immense locus heterogeneity and complex genetic architecture. In this study, we analyze exome/genome sequencing data from 873 probands with congenital vertebral malformation and 3794 control individuals. Clinical interpretation identifies Mendelian etiologies in 12.0% of the probands and reveals a muscle-related disease mechanism. Gene-based burden test of ultra-rare variants identifies risk genes with large effect sizes (ITPR2, TBX6, TPO, H6PD, and SEC24B). To further investigate the biological relevance of the genetic association signals, we perform single-nucleus RNAseq on human embryonic spines. The burden test signals are enriched in the notochord at early developmental stages and myoblast/myocytes at late stages, highlighting their critical roles in the developing spine. Our work provides insights into the developmental biology of the human spine and the pathogenesis of spine malformation.

Abstract Background Some studies have suggested that hepatitis B virus (HBV) infection had a negative association with semen quality, but the conclusions have been inconsistent. The purpose of our study was to systematically assess the association between HBV infection and semen parameters. Methods We searched electronic databases for studies published from January 1980 to August 2023. Eleven studies were included in the analysis. Primary outcomes were semen volume, sperm concentration, sperm morphology, sperm motility and sperm progressive motility. We also conducted a subgroup analysis between China and other countries. Result Compared with the semen quality of HBV-negative men, HBV infection had a negative association with semen volume (MD: −0.20 mL, 95%CI: −0.32 to − 0.09, P = 0.0004), sperm concentration (MD: −4.46 × 106/mL, 95%CI: −7.09 to − 1.84, P = 0.0009), sperm morphology (MD: −2.49%, 95%CI: −4.35 to − 0.64, P = 0.008), sperm motility (MD: −6.85%, 95%CI: −11.53 to − 2.18, P = 0.004), and sperm progressive motility (MD: −6.63%, 95%CI: −10.24 to − 3.02, P = 0.0003). However, HBV infection had no significant association with total sperm count (MD: −31.50 × 106, 95%CI: −74.11 to 11.10, P = 0.15). The association between HBV and semen quality were inconsistent between the subgroups. Conclusion HBV infection had a negative association with sperm concentration, motility, morphology, and semen volume. However, The association between HBV and total sperm count remain unclear. This metaanalysis suggests that we should pay attention to the adverse effect of HBV on sperm quality, and several studies have reported the relevant mechanisms. But due to the significant heterogeneity among studies on some semen parameters, further large and well-designed researches are needed before introducing clinical management recommendations.

Abstract Objective To analyse the anterior teeth effects of clear aligners on five different patterns of mandibular molar movement and to define the most effective configuration to be implemented with clear aligners through finite element analysis. Methods A three-dimensional mandibular model with a deep overbite in the mandible was constructed using cone beam computerized tomography (CBCT) data. The model included the mandibular dentition, mandibular periodontal ligaments, attachments, and aligners. Five models were created: (1) configuration A: second molar distalization (0.25 mm); (2) configuration B: second molar distalization (0.25 mm), first molar extrusion (0.15 mm); (3) configuration C: second molar distalization (0.25 mmm), first and second premolar extrusion(0.15 mm); (4) configuration D: second molar distalization (0.25 mm), first molar and first/second premolar extrusion(0.15 mm); and (5) configuration E: second molar distalization (0.25 mm), first molar and first/second premolar extrusion (0.15 mm), first molar and first/second premolar expansion (0.15 mm). Results In all configurations, the anterior teeth exhibited labial tipping and the mandibular central incisor of configuration E showed the highest labial tipping. Configuration E demonstrated a relatively minor impact on mandibular molars distalization compared with configuration A. Configuration A showed the highest distal displacement value, and configuration E produced the lowest displacement value. Configuration E caused the highest periodontal ligament (PDL) pressure of the central and lateral incisors. The differences in the canines between configurations C and D,were not significant, and the stress distribution differed among the five groups. Conclusions All patterns utilizing clear aligners facilitated mandibular molar distalization. Extruding the premolars and second molar distalization at the same time had little impact on second molar distalization; When expansion and extrusion were simultaneously performed during the distalization of mandibular molars, our prime consideration was the alveolar bone on the labial side of the anterior teeth to prevent the occurrence of gingival recession, dehiscence, and fenestration. Due to the lack of consideration for periodontal tissues in this study, clinical protocols should be designed based on the periodontal status of the mandibular anterior teeth.

Abstract Background The excretory/secretory (ES) antigen of Trichinella spiralis muscle larvae (ML) is currently the most widely used diagnostic antigen to detect T. spiralis infection. However, this antigen has certain drawbacks, such as a complicated ES antigen preparation process and lower sensitivity during the early phase of infection. The aim of this study was to investigate the features of a novel T. spiralis trypsin (TsTryp) and evaluate its potential diagnostic value for trichinellosis. Methods The TsTryp gene was cloned and recombinant TsTryp (rTsTryp) expressed. Western blotting and an enzyme-linked immunosorbent assay (ELISA) were performed to confirm the antigenicity of rTsTryp. The expression pattern and distribution signature of TsTryp at various life-cycle stages of T. spiralis were analyzed by quantitative PCR, western blotting and the immunofluorescence test. An ELISA with rTsTryp and ML ES antigens was used to detect immunoglobulins G and M (IgG, IgM) in serum samples of infected mice, swine and humans. The seropositive results were further confirmed by western blot with rTsTryp and ML ES antigens. Results TsTryp expression was observed in diverse T. spiralis life-cycle phases, with particularly high expression in the early developmental phase (intestinal infectious larvae and adults), with distribution observed mainly at the nematode outer cuticle and stichosome. rTsTryp was identified by T. spiralis-infected mouse sera and anti-rTsTryp sera. Natural TsTryp protease was detected in somatic soluble and ES antigens of the nematode. In mice infected with 200 T. spiralis ML, serum-specific IgG was first detected by rTsTryp-ELISA at 8 days post-infection (dpi), reaching 100% positivity at 12 dpi, and first detected by ES-ELISA at 10 dpi, reaching 100% positivity at 14 dpi. Specific IgG was detected by rTsTryp 2 days earlier than by ES antigens. When specific IgG was determined in serum samples from trichinellosis patients, the sensitivity of rTsTryp-ELISA and ES antigens-ELISA was 98.1% (51/52 samples) and 94.2% (49/52 samples), respectively (P = 0.308), but the specificity of rTsTryp was significantly higher than that of ES antigens (98.7% vs. 95.4%; P = 0.030). Additionally, rTsTryp conferred a lower cross-reaction, with only three serum samples in total testing positive from 11 clonorchiasis, 20 cysticercosis and 24 echinococcosis patients (1 sample from each patient group). Conclusions TsTryp was shown to be an early and highly expressed antigen at intestinal T. spiralis stages, indicating that rTsTryp represents a valuable diagnostic antigen for the serodiagnosis of early Trichinella infection. Graphical Abstract

Abstract Bile acids play important roles in lipid metabolism and glucose homeostasis. Limited research exist on the association between serum total bile acid (TBA) levels and major adverse cardiovascular events (MACEs) in patients with acute coronary syndrome (ACS), particularly those with comorbid type 2 diabetes mellitus (T2DM). This study was conducted to examine the relationship between baseline serum TBA level and T2DM status in patients with ACS after percutaneous coronary intervention (PCI) and to identify the predictive value of TBA levels for a 2-year risk of MACEs. 425 ACS patients underwent PCI were recruited and divided into three groups based on baseline serum TBA concentration. An analysis of the association between the T2DM status and baseline serum TBA levels was conducted using univariate linear regression and multivariate linear regression. The predictive relevance of serum TBA levels was evaluated using the receiver operating characteristic (ROC) curve and Cox regression. Kaplan–Meier curves were employed to analyze the differences among groups in predicting MACEs over a 2-year follow-up period. Baseline serum TBA levels were higher in ACS patients who were diagnosed with T2DM (the median 3.6 µmol/L) than those without T2DM (the median 3.0 µmol/L). T2DM status in ACS patients was positively correlated with baseline serum TBA concentrations (β: 1.7, 95% confidence interval [CI] 0.3–3.0), particularly in the male (β: 2.0, 95% CI 0.3–3.6) and 50–69-year-old (β: 2.5, 95% CI 0.6–4.4) populations. The areas under the ROC curve of baseline serum TBA levels predicted MACEs in ACS and ACS-T2DM patients following PCI were 0.649 (95% CI 0.595–0.703) and 0.783 (95% CI 0.685–0.881), respectively. Furthermore, Cox regression analysis showed that baseline serum TBA level was associated with the occurrence of MACEs in patients with ACS after PCI over a 2-year follow-up period, especially in those diagnosed with T2DM, whose baseline TBA concentration was lower than 10.0 µmol/L. ACS Patients with T2DM had higher serum TBA levels. TBA level at baseline was an independent predictor of MACEs in ACS patients who underwent PCI, especially with comorbid T2DM.

Periodontal ligament stem cells (PDLSCs) have the potential for multidirectional differentiation and are the preferred seed cells for periodontal tissue regeneration. In recent years, a large number of studies have confirmed that PDLSCs also possess broad immunomodulatory properties. Therefore, in-depth exploration of their specific molecular mechanisms is of great significance for the treatment of periodontitis. The aim of this paper is to summarize the research progress on the regulation of PDLSCs on various immune cells and the effect of the inflammatory environment on the immune characteristics of PDLSCs to provide an important theoretical basis for the allotransplantation of PDLSCs and improve the therapeutic effect of periodontal tissue regeneration. Studies have shown that PDLSCs possess a certain degree of immunosuppressive effect on both innate and acquired immune cells, and inflammatory stimulation may lead to the impairment of the immunoregulatory properties of PDLSCs. However, current studies are mainly limited to in vitro cell tests and lack in-depth studies on the immunomodulatory effects of PDLSCs in vivo. In vivo studies based on cell lineage tracing and conditional gene knockout technology may become the main directions for future research.

Abstract Background Ovarian clear cell carcinoma (OCCC) represents a subtype of ovarian epithelial carcinoma (OEC) known for its limited responsiveness to chemotherapy, and the onset of distant metastasis significantly impacts patient prognoses. This study aimed to identify potential risk factors contributing to the occurrence of distant metastasis in OCCC. Methods Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, we identified patients diagnosed with OCCC between 2004 and 2015. The most influential factors were selected through the application of Gaussian Naive Bayes (GNB) and Adaboost machine learning algorithms, employing a Venn test for further refinement. Subsequently, six machine learning (ML) techniques, namely XGBoost, LightGBM, Random Forest (RF), Adaptive Boosting (Adaboost), Support Vector Machine (SVM), and Multilayer Perceptron (MLP), were employed to construct predictive models for distant metastasis. Shapley Additive Interpretation (SHAP) analysis facilitated a visual interpretation for individual patient. Model validity was assessed using accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and the area under the receiver operating characteristic curve (AUC). Results In the realm of predicting distant metastasis, the Random Forest (RF) model outperformed the other five machine learning algorithms. The RF model demonstrated accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and AUC (95% CI) values of 0.792 (0.762–0.823), 0.904 (0.835–0.973), 0.759 (0.731–0.787), 0.221 (0.186–0.256), 0.974 (0.967–0.982), 0.353 (0.306–0.399), and 0.834 (0.696–0.967), respectively, surpassing the performance of other models. Additionally, the calibration curve's Brier Score (95%) for the RF model reached the minimum value of 0.06256 (0.05753–0.06759). SHAP analysis provided independent explanations, reaffirming the critical clinical factors associated with the risk of metastasis in OCCC patients. Conclusions This study successfully established a precise predictive model for OCCC patient metastasis using machine learning techniques, offering valuable support to clinicians in making informed clinical decisions.

PurposeAlcohol consumption increases the risk of breast cancer and promotes cancer progression. Alcohol exposure could affect both processes of the mammary carcinogenesis, namely, the cell transformation and onset of tumorigenesis as well as cancer aggressiveness including metastasis and drug resistance/recurrence. However, the cellular and molecular mechanisms underlying alcohol tumor promotion remain unclear. There are four members of the mammalian p38 mitogen-activated protein kinase (MAPK) family, namely, p38α, p38β, p38γ and p38δ. We have previously demonstrated alcohol exposure selectively activated p38γ MAPK in breast cancer cells in vitro and in vivo. Pirfenidone (PFD), an antifibrotic compound approved for the treatment of idiopathic pulmonary fibrosis, is also a pharmacological inhibitor of p38γ MAPK. This study aimed to determine whether PFD is useful to inhibit alcohol-induced promotion of breast cancer.MethodsFemale adolescent (5 weeks) MMTV-Wnt1 mice were exposed to alcohol with a liquid diet containing 6.7% ethanol. Some mice received intraperitoneal (IP) injection of PFD (100 mg/kg) every other day. After that, the effects of alcohol and PFD on mammary tumorigenesis and metastasis were examined.ResultsAlcohol promoted the progression of mammary tumors in adolescent MMTV-Wnt1 mice. Treatment of PFD blocked tumor growth and alcohol-promoted metastasis. It also significantly inhibited alcohol-induced tumorsphere formation and cancer stem cell (CSC) population.ConclusionPFD inhibited mammary tumor growth and alcohol-promoted metastasis. Since PFD is an FDA-approved drug, the current findings may be helpful to re-purpose its application in treating aggressive breast cancer and alcohol-promoted mammary tumor progression.

Abstract Background The incidence and prevalence of nonalcoholic fatty liver disease related hepatocellular carcinoma (NAFLD-HCC) are rapidly increasing worldwide. This study aimed to identify biomarker genes for prognostic prediction model of NAFLD-HCC hepatectomy by integrating text-mining, clinical follow-up information, transcriptomic data and experimental validation. Methods The tumor and adjacent normal liver samples collected from 13 NAFLD-HCC and 12 HBV-HCC patients were sequenced using RNA-Seq. A novel text-mining strategy, explainable gene ontology fingerprint approach, was utilized to screen NAFLD-HCC featured gene sets and cell types, and the results were validated through a series of lab experiments. A risk score calculated by the multivariate Cox regression model using discovered key genes was established and evaluated based on 47 patients’ follow-up information. Results Differentially expressed genes associated with NAFLD-HCC specific tumor microenvironment were screened, of which FABP4 and VWF were featured by previous reports. A risk prediction model consisting of FABP4, VWF, gender and TNM stage were then established based on 47 samples. The model showed that overall survival in the high-risk score group was lower compared with that in the low-risk score group (p = 0.0095). Conclusions This study provided the landscape of NAFLD-HCC transcriptome, and elucidated that our model could predict hepatectomy prognosis with high accuracy.

Abstract Objective The aim of this study was to determine whether serum vitamin D levels are associated with H. pylori infection and whether low serum vitamin D levels are an independent risk factor for H. pylori infection. Methods We conducted a retrospective analysis of a multicenter cohort study from 2017 to 2019. A total of 415 H. pylori + patients and 257 H. pylori − patients aged between 18 and 75 years with both 13 C-urea breath test and serum vitamin D level results were included from four hospitals. A questionnaire was used to collect information on potential factors influencing H. pylori infection. Results Serum vitamin D levels were significantly lower in the H. pylori + group than in the H. pylori − group (16.7 ± 6.6 ng/ml vs. 19.2 ± 8.0 ng/ml, p

Background Obstructive sleep apnea (OSA) has a high prevalence, and it has been shown to be an independent risk factor for various diseases. Therefore, it is important to strengthen screening for population at highrisk of OSA. OSA patients are prone to combine with lipid metabolism disorders, but it remains unclear whether the atherogenic index of plasma (AIP), visceral adiposity index (VAI), lipid accumulation product (LAP), cardiometabolic index (CMI), and Chinese visceral adiposity index (CVAI), which are used asmetabolic indexes, can be used to predict OSA. Objective To analyze the correlation between metabolic indexes and OSA, and evaluate the predictive efficacy of each metabolic index through a case-control study. Methods A total of 2 968 inpatients with suspected OSA and aged ≥18 years who completed polysomnography (PSG) in the First Affiliated Hospital of Xinjiang Medical University from March 2017 to June 2022 were selected, with 2 850 patients finally included based on the inclusion and exclusion criteria and divided into the OSA group 〔apnea-hypopnea index (AHI) ≥5 times/h, n=2 193〕 and non-OSA group (AHI0.05), but AIP and CVAI were associated with OSA (P

ABSTRACTUsing a sample of Chinese A-share listed firms on Shanghai and Shenzhen stock exchanges from year 2003–2019, this paper examines the impact of multiple large shareholders (MLS) on abnormal stock trading halts. The results reveal that listed companies with MLS have a lower probability of abnormal stock trading halts. When the number and share percentage of non-controlling shareholders increase, their inhibitory effect on arbitrary stock trading halts is more significant. Channel tests suggest that MLS can restrain abnormal stock trading halts by reducing the tunnelling activities by controlling shareholders, increasing the proportion of dissenting votes on corporate board, and improving corporate information disclosure quality. The impact of MLS on abnormal stock trading halts is more pronounced in firms with lower quality of internal control and information transparency.

Chronic obstructive pulmonary disease (COPD) is commonly caused by smoking. FUN14 domain-containing protein 1 (FUNDC1) plays a fundamental role in mitochondrial autophagy and apoptosis in cigarette smoke extract (CSE)-treated BEAS-2B cells. The present study investigated the mechanism of action of FUNDC1 in mitochondrial dysfunction and apoptosis in CSE-treated BEAS-2B cells. The interaction between ubiquitin-specific peptidase 19 (USP19) and FUNDC1 was analyzed using co-immunoprecipitation. Effects of USP19 knockdown and/or FUNDC1 overexpression on the survival, apoptosis, mitochondrial membrane potential, and oxygen consumption rate (OCR) of BEAS-2B cells treated with 15% CSE were determined. In BEAS-2B cells, CSE inhibited cell survival, promoted apoptosis, increased the expression of USP19 and FUNDC1, increased the ratio of LC3 II to LC3 I (LC3 II/I), and decreased mitochondrial membrane potential and TOM20 levels. In CSE-treated BEAS-2B cells, USP19 knockdown reduced FUNDC1 and LC3 II/I, increased the levels of TOM20, improved cell survival, mitochondrial membrane potential, and OCR, and inhibited apoptosis. USP19 deubiquitinates FUNDC1. FUNDC1 overexpression inhibited the effect of USP19 knockdown in CSE-treated BEAS-2B cells. Overall, decreasing USP19 expression alleviates CSE-induced mitochondrial dysfunction in BEAS-2B cells by downregulating FUNDC1, providing novel insights into the molecular mechanism of FUNDC1 regulation in COPD.

Increasing evidences suggest the important role of calcium homeostasis in hallmarks of cancer, but its function and regulatory network in metastasis remain unclear. A comprehensive investigation of key regulators in cancer metastasis is urgently needed. Transcriptome sequencing (RNA-seq) of primary esophageal squamous cell carcinoma (ESCC) and matched metastatic tissues and a series of gain/loss-of-function experiments identified potassium channel tetramerization domain containing 4 (KCTD4) as a driver of cancer metastasis. KCTD4 expression was found upregulated in metastatic ESCC. High KCTD4 expression is associated with poor prognosis in patients with ESCC and contributes to cancer metastasis in vitro and in vivo. Mechanistically, KCTD4 binds to CLIC1 and disrupts its dimerization, thus increasing intracellular Ca2+ level to enhance NFATc1-dependent fibronectin transcription. KCTD4-induced fibronectin secretion activates fibroblasts in a paracrine manner, which in turn promotes cancer cell invasion via MMP24 signaling as positive feedback. Furthermore, a lead compound K279-0738 significantly suppresses cancer metastasis by targeting the KCTD4‒CLIC1 interaction, providing a potential therapeutic strategy. Taken together, our study not only uncovers KCTD4 as a regulator of calcium homeostasis, but also reveals KCTD4/CLIC1-Ca2+-NFATc1-fibronectin signaling as a novel mechanism of cancer metastasis. These findings validate KCTD4 as a potential prognostic biomarker and therapeutic target for ESCC.

Abstract Tuning the composition of perovskites to approach the ideal bandgap raises the single-junction Shockley-Queisser efficiency limit of solar cells. The rapid development of narrow-bandgap formamidinium lead triiodide-based perovskites has brought perovskite single-junction solar cell efficiencies up to 26.1%. However, such compositional engineering route has reached the limit of the Goldschmidt tolerance factor. Here, we experimentally demonstrate a resonant perovskite solar cell that produces giant light absorption at the perovskite band edge with tiny absorption coefficients. We design multiple guide-mode resonances by momentum matching of waveguided modes and free-space light via Brillouin-zone folding, thus achieving an 18-nm band edge extension and 1.5 mA/cm2 improvement of the current. The external quantum efficiency spectrum reaches a plateau of above 93% across the spectral range of ~500 to 800 nm. This resonant nanophotonics strategy translates to a maximum EQE-integrated current of 26.0 mA/cm2 which is comparable to that of the champion single-crystal perovskite solar cell with a thickness of ~20 μm. Our findings break the ray-optics limit and open a new door to improve the efficiency of single-junction perovskite solar cells further when compositional engineering or other carrier managements are close to their limits.

Abstract The enolimine-ketoenamine tautomerism has been utilised to construct 2D covalent organic frameworks (COFs) with a higher level of chemical robustness and superior photoelectronic activity. However, it remains challenging to fully control the tautomeric states and correlate their tautomeric structure-photoelectronic properties due to the mobile equilibrium of proton transfer between two other atoms. We show that symmetry-asymmetry tautomerisation from diiminol to iminol/cis-ketoenamine can be stabilised and switched in a crystalline, porous, and dynamic 3D COF (dynaCOF-301) through concerted structural transformation and host-guest interactions upon removal and adaptive inclusion of various guest molecules. Specifically, the tautomeric dynaCOF-301 is constructed by linking the hydroquinone with a tetrahedral building block through imine linkages to form 7-fold interwoven diamondoid networks with 1D channels. Reversible framework deformation and ordering-disordering transition are determined from solvated to activated and hydrated phases, accompanied by solvatochromic and hydrochromic effects useful for rapid, steady, and visual naked-eye chemosensing.

Abstract Alpha-fetoprotein (AFP)-secreting hepatocellular carcinoma (HCC), which accounts for ~75% of HCCs, is more aggressive with a worse prognosis than those without AFP production. The mechanism through which the interaction between tumors and the microenvironment leads to distinct phenotypes is not yet clear. Therefore, our study aims to identify the characteristic features and potential treatment targets of AFP-negative HCC (ANHC) and AFP-positive HCC (APHC). We utilized single-cell RNA sequencing to analyze 6 ANHC, 6 APHC, and 4 adjacent normal tissues. Integrated multi-omics analysis together with survival analysis were also performed. Further validation was conducted via cytometry time-of-flight on 30 HCCs and multiplex immunohistochemistry on additional 59 HCCs. Our data showed that the genes related to antigen processing and interferon-γ response were abundant in tumor cells of APHC. Meanwhile, APHC was associated with multifaceted immune distortion, including exhaustion of diverse T cell subpopulations, and the accumulation of tumor-associated macrophages (TAMs). Notably, TAM-SPP1+ was highly enriched in APHC, as was its receptor CD44 on T cells and tumor cells. Targeting the Spp1-Cd44 axis restored T cell function in vitro and significantly reduced tumor burden when treated with either anti-Spp1 or anti-Cd44 antibody alone or in combination with anti-Pd-1 antibody in the mouse model. Furthermore, elevated IL6 and TGF-β1 signaling contributed to the enrichment of TAM-SPP1+ in APHC. In conclusion, this study uncovered a highly suppressive microenvironment in APHC and highlighted the role of TAM-SPP1+ in regulating the immune microenvironment, thereby revealing the SPP1-CD44 axis as a promising target for achieving a more favorable immune response in APHC treatment.

BackgroundMyopia poses a global health concern and is influenced by both genetic and environmental factors. The incidence of myopia tends to increase during infectious outbreaks, such as the COVID-19 pandemic. This study examined the screen-time behaviors among Chinese children and adolescents and investigated the efficacy of artificial intelligence (AI)-based alerts in modifying screen-time practices.MethodsA cross-sectional analysis was performed using data from 6,716 children and adolescents with AI-enhanced tablets that monitored and recorded their behavior and environmental light during screen time.ResultsThe median daily screen time of all participants was 58.82 min. Among all age groups, elementary-school students had the longest median daily screen time, which was 87.25 min and exceeded 4 h per week. Children younger than 2 years engaged with tablets for a median of 41.84 min per day. Learning accounted for 54.88% of participants’ screen time, and 51.03% (3,390/6,643) of the participants used tablets for 1 h at an average distance

Abstract Zn‐ion batteries are regarded as the most promising batteries for next‐generation, large‐scale energy storage because of their low cost, high safety, and eco‐friendly nature. The use of aqueous electrolytes results in poor reversibility and leads to many challenges related to the Zn anode. Electrolyte additives can effectively address many such challenges, including dendrite growth and corrosion. This review provides a comprehensive introduction to the major challenges in and current strategies used for Zn anode protection. In particular, an in‐depth and fundamental understanding is provided of the various functions of electrolyte additives, including electrostatic shielding, adsorption, in situ solid electrolyte interphase formation, enhancing water stability, and surface texture regulation. Potential future research directions for electrolyte additives used in aqueous Zn‐ion batteries are also discussed.

Abstract Conversion‐type electrodes offer a promising multielectron transfer alternative to intercalation hosts with potentially high‐capacity release in batteries. However, the poor cycle stability severely hinders their application, especially in aqueous multivalence‐ion systems, which can fundamentally impute to anisotropic ion diffusion channel collapse in pristine crystals and irreversible bond fracture during repeated conversion. Here, an amorphous bismuth sulfide (a‐BS) formed in situ with unprecedentedly self‐controlled moderate conversion Cu2+ storage is proposed to comprehensively regulate the isotropic ion diffusion channels and highly reversible bond evolution. Operando synchrotron X‐ray diffraction and substantive verification tests reveal that the total destruction of the Bi─S bond and unsustainable deep alloying are fully restrained. The amorphous structure with robust ion diffusion channels, unique self‐controlled moderate conversion, and high electrical conductivity discharge products synergistically boosts the capacity (326.7 mAh g−1 at 1 A g−1), rate performance (194.5 mAh g−1 at 10 A g−1), and long‐lifespan stability (over 8000 cycles with a decay rate of only 0.02 ‰ per cycle). Moreover, the a‐BS Cu2+‖Zn2+ hybrid ion battery can well supply a stable energy density of 238.6 Wh kg−1 at 9760 W kg−1. The intrinsically high‐stability conversion mechanism explored on amorphous electrodes provides a new opportunity for advanced aqueous storage.

BackgroundProteases secreted by Trichinella spiralis intestinal infective larvae (IIL) play an important role in larval invasion and pathogenesis. However, the mechanism through which proteases mediate larval invasion of intestinal epithelial cells (IECs) remains unclear. A novel T. spiralis trypsin (TsTryp) was identified in IIL excretory/secretory (ES) proteins. It was an early and highly expressed protease at IIL stage, and had the potential as an early diagnostic antigen. The aim of this study was to investigate the biological characteristics of this novel TsTryp, its role in larval invasion of gut epithelium, and the mechanisms involved.Methodology/principal findingTsTryp with C-terminal domain was cloned and expressed in Escherichia coli BL21 (DE3), and the rTsTryp had the enzymatic activity of natural trypsin, but it could not directly degrade gut tight junctions (TJs) proteins. qPCR and western blotting showed that TsTryp was highly expressed at the invasive IIL stage. Immunofluorescence assay (IFA), ELISA and Far Western blotting revealed that rTsTryp specifically bound to IECs, and confocal microscopy showed that the binding of rTsTryp with IECs was mainly localized in the cytomembrane. Co-immunoprecipitation (Co-IP) confirmed that rTsTryp bound to protease activated receptors 2 (PAR2) in Caco-2 cells. rTsTryp binding to PAR2 resulted in decreased expression levels of ZO-1 and occludin and increased paracellular permeability in Caco-2 monolayers by activating the extracellular regulated protein kinases 1/2 (ERK1/2) pathway. rTsTryp decreased TJs expression and increased epithelial permeability, which could be abrogated by the PAR2 antagonist AZ3451 and ERK1/2 inhibitor PD98059. rTsTryp facilitated larval invasion of IECs, and anti-rTsTryp antibodies inhibited invasion. Both inhibitors impeded larval invasion and alleviated intestinal inflammation in vitro and in vivo.ConclusionsTsTryp binding to PAR2 activated the ERK1/2 pathway, decreased the expression of gut TJs proteins, disrupted epithelial integrity and barrier function, and consequently mediated larval invasion of the gut mucosa. Therefore, rTsTryp could be regarded as a potential vaccine target for blocking T. spiralis invasion and infection.

IntroductionThe under representation of women in STEM fields is a persistent issue worldwide. In China, although women have made significant progress in pursuing STEM degrees in recent years, they continue to face challenges in the workforce. Given the importance of the self-perceived employability (SPE) of female STEM students in China, the research questions are: How do curriculum experience, extracurricular experience, and faculty supportive activities affect the SPE of female STEM students in Chinese universities? To what extent does university stratification affect the relationship between college experience and female STEM students’ SPE?MethodsWe analyzed the 2018 data of the Chinese College Student Survey (CCSS) consisting of a sample of 59,066 students, and six focus group interviews.ResultsThe findings suggest that curriculum experience, extracurricular experience and faculty supportive activities have a positive impact on the SPE of female students, but the gender gap in SPE is still valid as reflected by the fact that women have lower SPE than men in each tier of universities and that men benefit more in terms of the increase in SPE from most types of college activities and support except academic ones.DiscussionThis study reveals that the different tiers of universities in China affect female students’ SPE in different ways, and provides valuable evidence for academic as well as university administrators and policymakers regarding how college experience affect women and how university stratification can affect female students’ college experience and their career expectations and paths.

AbstractThe present study evaluated the presentations and outcomes of coronavirus disease 2019 (COVID-19) among patients undergoing maintenance hemodialysis (MHD) and the impact of the Omicron BF.7 variant. Adult patients (age ≥ 18 years), who underwent MHD (dialysis vintage ≥ 3 months) at the Hemodialysis Center at Beijing Tsinghua Changgung Hospital between December 2022 and January 2023, were included based on predefined eligibility criteria. Clinical and laboratory characteristics were retrospectively collected. Among 131 patients who underwent MHD (10.7% vaccination rate), 106 (80.9%) tested positive for COVID-19. The prevalence of asymptomatic, mild, moderate, and severe COVID-19 was 8.5%, 58.5%, 17%, and 16%, respectively. Among the 97 patients with symptoms, 23 (23.7%) were hospitalized and six (5.7%) died. Fever was experienced by 74.2% of patients and respiratory symptoms were the most common (81.4%). Residual symptoms persisted in 20.9% of patients one month after the onset of COVID-19. COVID-19-positive hemodialysis patients were more likely to experience weight loss and exhibit reduced albumin levels compared to those without COVID-19 (p

The introduction of mobile edge computing (MEC) technology in rail transit which has the characteristics of complex environment, high densities of passengers, and high-speed mobility can meet the low latency, mobility, and massive connection requirements of rail transit.However, MEC not only improves the performance of rail transit communication network but also brings security challenges.Firstly, an overview of rail transit communication network and MEC was given.Then the value of introducing MEC into rail transit and the architecture of rail transit edge computing network were discussed.After that, the security threats faced by rail transit edge computing network was analyzed and protection scheme was proposed.Finally, some open questions were proposed, which was expected to provide ideas for future research.

ABSTRACTThe stock price index is a thermometer reflecting changes in the stock market, and can convey key information on capital market dynamics and trends to investors. This paper empirically investigates the impact of index adjustments on corporate social responsibility performance by employing the quasi-natural experiment of CSI 300 index adjustments. We find that index additions significantly promote corporate social responsibility performance. Mechanism analysis supports the shareholder value maximisation motivation that drives the fulfilment of corporate social responsibility. In addition, more analyst following and investor attention plays a significant mediating role in the promotion impact of stock index additions on corporate social responsibility. Further analyses show that the positive impact of the stock index additions on corporate social responsibility performance is more pronounced in industries with more competitive product market. However, index deletions do not significantly reduce corporate social responsibility performance, implying that index additions and index deletions have asymmetric effects.

The use of heat pipes (HP) for the DEMO in-vessel plasma-facing components (PFCs) has been considered because of their high capacity to transport the heat from a heat source to a heat sink by means of the vaporization and condensation of the working fluid inside and their ability to enlarge the heat transfer area of the cooling circuit substantially. Recent engineering studies conducted in the framework of the EUROfusion work package Divertor (Wen et al, 2021) indicate that it is possible to design a heat pipe with a capillary limit above 6 kW using a composite capillary structure (wherein axial grooves cover the adiabatic zone and the condenser, and sintered porous material covers the evaporator). This power level would correspond to an applied heat flux of 20 MW/m2, rendering such a design interesting with respect to a divertor target concept. To validate the results of the initial engineering analysis, several experiments have been conducted to evaluate the actual performance of the proposed heat pipe concept. The present contribution presents the experiment’s results regarding the examination of the operating limits of two different designs for an evaporator: one featuring a plain porous structure, and one featuring ribs and channels.

Objective: To describe the pain intensity among hospitalized patients with calciphylaxis, elucidate the factors associated with pain improvement, and examine the link between pain improvement and clinical outcomes. Patients and Methods: Patients were identified from the Partners Research Patient Data Registry and the Partners Calciphylaxis Registry and Biorepository (Clinicaltrials.gov ID: NCT03032835). Those with calciphylaxis requiring hospitalization for at least 14 consecutive days during the study period from May 2016 through December 2021 were included. Pain intensity was assessed using patient-reported pain scores on numerical rating scales from 0 to 10. Associations between pain improvement and clinical outcomes, including lesion improvement, amputation, and mortality, were examined using univariate and multivariate regression models. Results: Our analysis included 111 patients (age, 58±14 years; men, 40%; on maintenance dialysis, 79%). No significant improvement of pain intensity was observed over the 14 days of hospitalization (mean difference, −0.71; P=.08). However, among 49 (44.1%) patients who showed at least 1-point improvement in the pain score, there was an association with surgical debridement during hospitalization (odds ratio, 3.37; 95% CI, 1.17-9.67; P=.02). Hyperbaric oxygen therapy was associated with pain improvement (odds ratio, 5.38; 95% CI, 1.14-25.50; P=.03) in patients on maintenance dialysis. Pain improvement was associated with lower rates of subsequent amputation at 6 months of follow up (6% vs 13%; P

Organic macrocycles and cages have been well-developed as porous solids for gas detection but balancing adaptability and robustness in these materials remains challenging. Here, the authors report a dynamic 3D covalent organic framework that can undergo concerted and adaptive structural transitions upon adsorption of gas and vapours.

Abstract Background Brain edema is a rare and serious complication of assisted reproductive technology (ART). The increased intracranial pressure and injured brain parenchyma are life-threatening and may even result in death. The pathogenesis may involve increased vascular permeability mediated by vascular endothelial growth factor and other vasoactive substances, including interleukin 6, interleukin 1β, angiotensin II, insulin-like growth factor 1, transforming growth factor β, and the renin–angiotensin system. Case presentation We presented a unique case report of a 29-year-old woman developed sudden irritability, blurred consciousness, and vomiting 8 h after oocyte retrieval. Blood examinations showed hyponatremia and cranial computed tomography showed swelling of the brain parenchyma. After therapeutic use of hypertonic saline and mannitol infusion, the patient’s consciousness recovered and her neurological state improved. Conclusions Brain edema is a rare and serious complication of ART. Quick infusion of hypertonic salt solution and mannitol is a key treatment. A good prognosis can be achieved after prompt treatment.