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Abstract Introduction Hypertensive intracerebral hemorrhage (HICH) is a condition associated with significant morbidity, mortality, and disability, particularly among the elderly population. The management of moderate thalamic-basal ganglia cerebral hemorrhage primarily relies on conservative approaches. Nevertheless, the rate of long-term disability remains high. In recent years, there has been significant advancement in minimally invasive surgery and diffusion tensor imaging techniques. Consequently, the utilization of Diffusion Tensor Imaging (DTI) technology in patients with cerebral haemorrhage allows for the identification of the haematoma’s location in relation to the Corticospinal Tract (CST). This enables the development of precise puncture pathways that can be visualized, thereby avoiding any potential damage to the CST. Methods and analysis Diffusion Tensor Imaging (DTI) is a method used to assess the structural and physiological characteristics of biological tissue by examining the diffusion behavior of water molecules.In the central nervous system, limb paralysis will be inevitable if the corticospinal tract is damaged. By employing DTI imaging techniques on individuals, it becomes possible to visualize the spatial relationship between the hematoma and the CST. This approach allows avoidance of the CST during preoperative planning of the puncture path, thus reducing secondary injuries caused by the procedure. The primary objective of this study was to assess the ability of patients in the minimally invasive surgery group and the conservative group to perform activities of daily living after 6 months of treatment. In addition, secondary outcomes included assessment of hematoma resorption/clearance ratios, cytokine levels, complication rates, and therapeutic indexes at different treatment durations, as well as long-term safety and efficacy at 2–3 years of follow-up. Furthermore, subgroup analysis, and sensitivity analysis were conducted to further analyze the data. Logistic single-variate and multivariate regression analyses were applied to understand the adverse factors affecting prognosis. Ethics and dissemination The clinical study was reviewed and approved by the Ethics Committee of the First People’s Hospital of Yibin. The ethical number is: 2023 Review (64). Registration number This protocol is registered in the Prospective Registry of Chinese Clinical Trial Registries (PROCCTR). The full date of first registration is 28/12/2023. The registration number for PROCCTR is ChiCTR2300079252.

The choroid plexus (ChP) serves as the principal origin of cerebrospinal fluid (CSF). CSF hypersecretion due to ChP inflammation has emerged as an important pathogenesis of hydrocephalus recently. Nevertheless, the precise mechanisms of ChP inflammation and the ensuing CSF hypersecretion in hydrocephalus remain ill-defined. In the present study, we elucidate the critical role of macrophages in the pathogenesis of ChP inflammation. Specifically, we identify the chemokine CCL2, released by ChP epithelial cells, recruits CCR2+ monocytes to the ChP thereby inciting hydrocephalus pathogenesis. The accumulated ChP macrophages increase the inflammation in ChP epithelial cells through TNF-α/TNFR1/NF-κB signaling cascade, thereby leading to CSF hypersecretion. Strikingly, augmentation of ChP‒CCL2 using an adeno-associated viral approach (AAV) exacerbates macrophage recruitment, activation, and ventriculomegaly in rat PHH models. Systemic application of Bindarit, a specific CCL2 inhibitor, significantly inhibits ChP macrophage infiltration and activation and reduces CSF secretion rate. Furthermore, the administration of CCR2 antagonist (INCB 3284) reduces ChP macrophage accumulation and ventriculomegaly. This study not only unveils the ChP CCL2‒CCR2 signaling in the pathophysiology of hydrocephalus but also unveils Bindarit as a promising therapeutic choice for the management of posthemorrhagic hydrocephalus.

To investigate different irradiation doses of Se-enriched A.Auricularia polysaccharide (SAAP) in type 1 diabetes mellitus (T1DM) mice. In this study, extraction of polysaccharides from selenium-enriched fungus was carried out after 60Co-γ-ray irradiation treatment. The optimal extraction conditions of SAAP were optimized by response surface methodology. The optimal irradiation dose was selected for the study of in vivo hypoglycemia by comparing the hypoglycemic effect of SAAP under different irradiation doses. C57BL/6 T1DM mice model was established by injecting streptozotocin (STZ) to evaluate the effects of fasting blood glucose (FBG), oral glucose tolerance (OGTT), and SAAP on the glucolipid metabolism and the regulation of oxidative stress in T1DM mice. The results showed that after response surface optimization, the optimal extraction conditions for SAAP: Material-liquid ratio of 37.98:1 mL/g, extraction temperature of 97.94 ℃, extraction time of 3.42 h. The optimal parameters were as follows: liquid-material ratio of 38:1 mL/g, extraction temperature 98 ℃, extraction time of 3.5 h, and SAAP concentration of 0.73 mg/mL. SAAP could improve the symptoms of polydipsia, polyphagia and weight loss in T1DM mice (P

Abstract Background The spatiotemporal epidemiological evidence supporting joint endoscopic screening for esophageal cancer (EC) and gastric cancer (GC) remains limited. This study aims to identify combined high-risk regions for EC and GC and determine optimal areas for joint and separate endoscopic screening. Methods We analyzed the association of incidence trends between EC and GC in cancer registry areas across China from 2006 to 2016 using spatiotemporal statistical methods. Based on these analyses, we divided different combined risk regions for EC and GC to implement joint endoscopic screening. Results From 2006 to 2016, national incidence trends for both EC and GC showed a decline, with an average annual percentage change of -3.15 (95% confidence interval [CI]: -5.33 to -0.92) for EC and -3.78 (95% CI: -4.98 to -2.56) for GC. A grey comprehensive correlation analysis revealed a strong temporal association between the incidence trends of EC and GC, with correlations of 79.00% (95% CI: 77.85 to 80.14) in males and 77.62% (95% CI: 76.50 to 78.73) in females. Geographic patterns of EC and GC varied, demonstrating both homogeneity and heterogeneity across different regions. The cancer registry areas were classified into seven distinct combined risk regions, with 33 areas identified as high-risk for both EC and GC, highlighting these regions as priorities for joint endoscopic screening. Conclusion This study demonstrates a significant spatiotemporal association between EC and GC. The identified combined risk regions provide a valuable basis for optimizing joint endoscopic screening strategies for these cancers.

Abstract Psoriasis is an immune-mediated skin disease associated with neurogenic inflammation, but the underlying molecular mechanism remains unclear. We demonstrate here that acid-sensing ion channel 3 (ASIC3) exacerbates psoriatic inflammation through a sensory neurogenic pathway. Global or nociceptor-specific Asic3 knockout (KO) in female mice alleviates imiquimod-induced psoriatic acanthosis and type 17 inflammation to the same extent as nociceptor ablation. However, ASIC3 is dispensable for IL-23-induced psoriatic inflammation that bypasses the need for nociceptors. Mechanistically, ASIC3 activation induces the activity-dependent release of calcitonin gene-related peptide (CGRP) from sensory neurons to promote neurogenic inflammation. Botulinum neurotoxin A and CGRP antagonists prevent sensory neuron-mediated exacerbation of psoriatic inflammation to similar extents as Asic3 KO. In contrast, replenishing CGRP in the skin of Asic3 KO mice restores the inflammatory response. These findings establish sensory ASIC3 as a critical constituent in psoriatic inflammation, and a promising target for neurogenic inflammation management.

Grouper, a species of coral reef fish, exhibits a wide geographical distribution within the warm waters of the tropical and subtropical regions across the globe, primarily inhabiting the middle and lower layers of water. Characterized as a substantial marine economic fish, grouper possesses considerable nutritional value, boasts a high market worth, and garners significant consumer demand. Its popularity among consumers is attributed to its inherent attributes, and it holds immense potential for further cultivation and breeding endeavors. This study utilized micro-satellite (MISA) software to investigate the distribution characteristics of microsatellites in the genomes of five grouper species (Epinephelus akaara, E.coioides, E.fuscoguttatus, E.lanceolatus, and E.moara). A custom script was developed to analyze the screening results, and statistical analyses were conducted on the microsatellite repeat types, duplicate copy types, and core copy numbers in the genomes of the five grouper species. Over 280 000 microsatellite sites were identified from the entire genomes of the five grouper species. The relative abundance of microsatellites ranged from 271–296, with a total length ranging from 6.30–7.06 Mb. The average length of the microsatellites was approximately 22 bp, and their proportion in the genomes ranged from 0.59%–0.67%. These results provide insights into the distribution characteristics of microsatellites in the genomes of these five grouper species and can inform future studies on their genomic architecture and evolution. The repetitive types of microsatellites were analyzed in terms of number, proportion, and relative abundance. The number, proportion, and relative abundance of repetitive types followed a consistent pattern, with the highest number of double base repeats, followed by single base repeats. This pattern decreased as the number of repeat units increased. A, AC, AAT, AAG, AGC, AATC, AAAT, AGAT, AATG, AGAGG, AAAAT, AAGAT, ACAGAG, AAANNN, and AANNNN (N represents any of the three bases except A) were the most dominant types of each duplicate copy type. Type A accounted for 90.00% of single base repeats, while type AC was the most dominant in double base repeats, accounting for nearly 80.00%. Interestingly, the content of the CG duplication category was the least, accounting for only 0.04%–0.10% in the five grouper species. This may be owing to the fact that the composition content of the four bases in the different species' genomes is different, and there may be structural problems with different bases. The results of this study provide insight into the distribution characteristics of microsatellites in the genomes of these five grouper species. The high frequency distribution of AGG and AGC in the dominant types of triple base repeats may play a crucial role in regulating genes involved in immunity, disease, and other genes in groupers. Previous studies show that AGG is a well-known binding site for numerous transcription factors involved in early growth and development of various species. Additionally, the change of base repeat polymorphism of the AGC category is directly linked to genetic diseases and holds significant evolutionary and medical research value. AAAN, AAAAN, and AAAAAN are dominant repeat types that are widely distributed in mammals among the four, five, and six base repeat types, respectively. Different types of microsatellites show significant variability in the number of core copy numbers. Nevertheless, the number of duplicate copies of each type of microsatellite exhibit a consistent trend in the five groupers, and the number of microsatellites decrease with an increase in the number of duplicate copies. The analysis of microsatellite distribution revealed several key findings. First, over 95% of single base repeat copies were concentrated in a range of 12 to 25 times. The main number of copies for two base repeats ranged from 6 to 32 times, with a small peak between 11 and 14 copies, and decreasing numbers with increasing copies. The number of copies for four and five base repeats was mainly concentrated in the ranges of 5–16 and 5–17, and 5–14, respectively. Notably, AGAT, AAAG, AAGAG, AATAT, and AGAGG repeats exhibited a large number of copies, even when the number of copies was high. The increase in copy number may represent changes in polymorphism at these loci that may lead to disease or changes in corresponding functions. Overall, these findings provide important insights into the distribution and potential functional significance of microsatellites in the genome of the studied species. The distribution characteristics of microsatellites in the genomes of the five groupers provide a valuable basis to understand the evolutionary mechanisms and functional expression of these species. The distribution of duplicate copy numbers of each type of duplication displays two peaks at 6 and 12 repetitions, with the number of microsatellites decreasing with increasing numbers of core copies. Some duplication types show particularly prominent numbers in specific species, such as T, TA, and AGACAG in E.lanceolatus, copied 502, 803, and 48 times respectively; GAG, CACT, and CCACA in E.moara, copied 205, 652, and 111 times respectively. These variations highlight the importance of exploring the role of microsatellite loci to develop a better understanding of the genetic distance and kinship among the five groupers. This analysis lays the groundwork to develop high-quality microsatellite molecular markers, and facilitates the selection of favorable varieties and the development of new varieties. In general, these research results provide important data to understand the genomic characteristics of the five groupers and helps to conduct advanced genetic research on these species.

Abstract Background The way of testicular tissue fixation directly affects the correlation and structural integrity between connective tissue and seminiferous tubules, which is essential for the study of male reproductive development. This study aimed to find the optimal fixative and fixation time to produce high-quality testicular histopathological sections, and provided a suitable foundation for in-depth study of male reproductive development with digital pathology technology. Methods Testes were removed from both sides of 25 male C57BL/6 mice. Samples were fixed in three different fixatives, 10% neutral buffered formalin (10% NBF), modified Davidson’s fluid (mDF), and Bouin’s Fluid (BF), for 8, 12, and 24 h, respectively. Hematoxylin and eosin (H&E) staining, periodic acid Schiff-hematoxylin (PAS-h) staining, and immunohistochemistry (IHC) were used to evaluate the testicle morphology, staging of mouse seminiferous tubules, and protein preservation. Aperio ScanScope CS2 panoramic scanning was used to perform quantitative analyses. Results H&E staining showed 10% NBF resulted in an approximately 15–17% reduction in the thickness of seminiferous epithelium. BF and mDF provided excellent results when staining acrosomes with PAS-h. IHC staining of synaptonemal complexes 3 (Sycp3) was superior in mDF compared to BF-fixed samples. Fixation in mDF and BF improved testis tissue morphology compared to 10% NBF. Conclusions Quantitative analysis showed that BF exhibited a very low IHC staining efficiency and revealed that mouse testes fixed for 12 h with mDF, exhibited morphological details, excellent efficiency of PAS-h staining for seminiferous tubule staging, and IHC results. In addition, the morphological damage of testis was prolonged with the duration of fixation time.

This study focused on examining the effects and mechanism of action of ginseng flower alcohol extract (GFAE) on a drug-induced liver injury (DILI) mice model. Ginseng blossoms were extracted with alcohol and examined for their principal active components using high performance liquid chromatography (HPLC), revealing that GFAE was made up of six ginsenoside active components. By creating a mouse model of DILI and measuring its relevant inflammatory indexes and related proteins, it was revealed that GFAE treats DILI by decreasing inflammatory factors, inhibiting inflammation and hepatocyte apoptosis, suppressing abnormal activation of the Phosphatidylinositol 3-Kinase/Protein Kinase B/Mammalian Rapamycin Target Protein (PI3K/AKT/mTOR) signaling pathway, and increasing beneficial bacteria in the intestinal tract, enhancing intestinal flora diversity, and improving the intestinal environment.

Lung cancer as a molecularly and histologically high heterogonous disease, there is an urgent need to predict lung cancer patients' responses to anti-cancer treatment, and patient-derived organoids (PDOs) have been recognized as a valuable platform for preclinical drug screening. In this study, we successfully established 26 PDO lines from various subtypes of lung cancers including benign tumor, adenocarcinoma, squamous cell carcinoma, adenosquamous carcinoma, large-cell carcinoma, and small-cell carcinoma. These PDOs were shown to retain the major genomic and histological characteristics of primary tumors and remain stable during long-term culture. With the help of targeted genomic sequencing, we found that lung cancer that harbors METN375S mutation is selectively sensitive to afatinib, and a combination of afatinib and gemcitabine induced synthetic lethality in PDO and mini-PDX models. In summary, our findings demonstrate the potential of PDO in predicting lung cancer drug response, and reveal a promising strategy for METN375S mutant lung cancer treatment.

Summary: Progression of acute traumatic brain injury (TBI) into chronic neurodegeneration is a major health problem with no protective treatments. Here, we report that acutely elevated mitochondrial fission after TBI in mice triggers chronic neurodegeneration persisting 17 months later, equivalent to many human decades. We show that increased mitochondrial fission after mouse TBI is related to increased brain levels of mitochondrial fission 1 protein (Fis1) and that brain Fis1 is also elevated in human TBI. Pharmacologically preventing Fis1 from binding its mitochondrial partner, dynamin-related protein 1 (Drp1), for 2 weeks after TBI normalizes the balance of mitochondrial fission/fusion and prevents chronically impaired mitochondrial bioenergetics, oxidative damage, microglial activation and lipid droplet formation, blood-brain barrier deterioration, neurodegeneration, and cognitive impairment. Delaying treatment until 8 months after TBI offers no protection. Thus, time-sensitive inhibition of acutely elevated mitochondrial fission may represent a strategy to protect human TBI patients from chronic neurodegeneration.

Abstract Objective Sex differences in outcomes of patients with aneurysmal subarachnoid hemorrhage (aSAH) remain controversial. Therefore, the aim of this study was to investigate the sex differences in the prognosis of patients with aSAH. Methods This study retrospectively analyzed the clinical data of aSAH patients admitted to the Department of Neurosurgery of General Hospital of Northern Theater Command, from April 2020 to January 2022. The modified Rankin Scale (mRS) was used to evaluate outcomes at 3-month post-discharge. Baseline characteristics, in-hospital complications and outcomes were compared after 1:1 propensity score matching (PSM). Results A total of 665 patients were included and the majority (63.8%) were female. Female patients were significantly older than male patients (59.3 ± 10.9 years vs. 55.1 ± 10.9 years, P

Abstract This paper proposes a prediction method for the tension force of support ropes in flexible rockfall barriers. The method is based on two full-scale model tests with an impact energy of 3000 kJ, as well as 36 set numerical models featuring varying lengths and impact energies. From the results of full scale tests and numerical models, it is inferred that the tension force at the end of the support rope is significantly less than that at the point of impact, exhibiting an approximate Gaussian attenuation distribution with propagation distance. To account for the attenuation of tensile forces in support ropes, a tensile attenuation coefficient is defined. Through comparative analysis of data obtained from 36 models with varying impact energies and propagation distances, the average attenuation coefficient for the upper support rope is determined to be approximately 0.7, while the average coefficient for the lower support rope is around 0.8. Utilizing the least squares method, a prediction method for the tension force of support ropes in flexible rockfall barriers is established. This method takes into account both the propagation distance and impact energy, enabling accurate predictions of the tensile behavior of the ropes under different conditions. This prediction model provides valuable insights for engineers in the design and optimization of these flexible barriers for rockfall mitigation.

Abstract Background The COVID-19 pandemic has resulted in widespread disruptions to primary healthcare delivery and shifts to virtual care. Reduced in-person paediatric primary care visit rates have been reported. However, the extent to which access to primary preventative care has been impacted remains unclear. The objective of this scoping review is to characterise the utilisation of preventative primary care and its association with child development for children ages 0–5 years old during the COVID-19 era. In addition, we will determine if specific groups of children are at greater risk for reduced access to care. Methods A systematic search will be conducted for studies published between March 11, 2020, and October 2023 in the following databases: MEDLINE (Ovid), Embase (Ovid), Cochrane Library (CENTRAL and CDSR), Web of Science, and CINAHL (EBSCOhost). This scoping review will follow the methodological framework developed by Arksey and O’Malley and updated by the Joanna Briggs Institute (JBI). Studies related to primary preventative care of children aged 0–5 years old conducted in English and in high-income countries will be screened. Studies published before March 11, 2020, in acute care and low–middle-income settings will be excluded. Results will be summarised for appointments attended, delayed, and missed. In addition, we will summarise findings on the impact of COVID-19 on child development. Findings will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. Discussion Further investigation is required to better understand the relationship between attendance of preventative primary care for children and its effects on child development. The findings obtained from this review will offer essential context to guide policy-making and healthcare service planning for the period following the pandemic.

Abstract The integrated design of traffic signal control (TSC) and reversible lane (RL) is an effective way to solve the problem of tidal congestion with uncertainty at isolated intersections, because of its advantage in making full use of temporal‐spatial transportation facilities. Considering the contradiction between the dynamic TSC scheme and the fixed RL scheme in one period, a two‐stage optimization method based on improved mean‐standard deviation (MSD) model for isolated intersections with historical and real‐time uncertain traffic flow is proposed. In the first stage, applying the same‐period historical data of multiple days, a robust optimal traffic signal control model with reversible lane based on MSD model (MSD‐RTR model) is put forward to obtain the fixed RL scheme and the compatible initial TSC scheme. A double‐layer nested genetic algorithm (DN‐GA) is designed to solve this model. In the second stage, applying real‐time period data and multi‐day same‐period historical data, a robust optimal dynamic traffic signal control model based on MSD model (MSD‐RDT model) is put forward to obtain the dynamic TSC scheme. Three modes which reflect the different weights of historical period and real‐time period in this MSD‐RDT model are presented to improve the model stability, and a multi‐mode genetic algorithm (MM‐GA) is designed. Finally, a case study is presented to demonstrate the efficiency and applicability of the proposed models and algorithms.

AC induction motors have been widely used in various industries, and their sensorless control system has the advantages of simple structure and low cost. To realize sensorless control of the induction motor, the rotor flux and speed must be observed. The sliding mode observer has strong robustness and high observation accuracy; therefore, it has attracted considerable attention. In addition, in the induction motor control system, the high switching frequency of the inverter causes high loss to the switching device and reduces the service life of the inverter. Therefore, the inverter switching frequency should be reduced to the maximum achievable level during the control process. However, in the traditional low switching frequency control method based on space vector pulse-width-modulation (SVPWM), a decrease in the switching frequency reduces the sampling frequency of the system. Simultaneously, it increases the sampling time delay, reduces the control bandwidth, and directly affects the observation accuracy of the rotor flux observer in the sensorless control method, thereby resulting in a poor sensorless control effect. Predictive control has the characteristics of rolling optimization, which realizes a low switching frequency and ensures a high sampling frequency of the system, thus ensuring the observation accuracy of the observer and system control effect in the sensorless application scenario. Therefore, this paper proposes a sensorless control method for an induction motor with low switching frequency to solve the problem that the traditional control method adversely affects noninductive flux observation. The sensorless predictive control system of the induction motor is constructed by combining a speed adaptive sliding mode observer under the boundary confined predictive control method. This sensorless control system can effectively reduce the switching frequency at a high sampling frequency and ensure a high dynamic characteristic of the system. In addition, the introduction of the sliding mode makes the observer robust. Experimental results reveal that the proposed low switching frequency sensorless control strategy exhibits high control accuracy and strong anti-interference performance. The adaptive sliding mode observer has good observation accuracy in the steady state and dynamic experiments, and the current loop response time can reach 1.52 ms. Moreover, it can achieve stable observation and operation when the speed is higher than 75 r·min–1, and the highest average switching frequency of the system is maintained at about 500 Hz, which is a low level.

Abstract The United Nations’ Sustainable Development Goal (SDG) 3.9 calls for a substantial reduction in deaths attributable to PM2.5 pollution (DAPP). However, DAPP projections vary greatly and the likelihood of meeting SDG3.9 depends on complex interactions among environmental, socio-economic, and healthcare parameters. We project potential future trends in global DAPP considering the joint effects of each driver (PM2.5 concentration, death rate of diseases, population size, and age structure) and assess the likelihood of achieving SDG3.9 under the Shared Socioeconomic Pathways (SSPs) as quantified by the Scenario Model Intercomparison Project (ScenarioMIP) framework with simulated PM2.5 concentrations from 11 models. We find that a substantial reduction in DAPP would not be achieved under all but the most optimistic scenario settings. Even the development aligned with the Sustainability scenario (SSP1-2.6), in which DAPP was reduced by 19%, still falls just short of achieving a substantial (≥20%) reduction by 2030. Meeting SDG3.9 calls for additional efforts in air pollution control and healthcare to more aggressively reduce DAPP.

Objective: To investigate the optimal extraction process and antioxidant and anti-fatigue activities of ginseng adventitious roots total saponins (GARS). Methods: GARS was extracted using ethanol reflux method, and the effects of different factors such as ethanol concentration, solvent-to-solid ratio, extraction temperature, and extraction time on the content of GARS were studied by orthogonal test. The antioxidant and anti-fatigue activities of GARS were determined by measuring the scavenging abilities of DPPH, ABTS+, PTIO, ·OH, and O2−·, as well as the reducing power. The effects of GARS on the swimming and climbing times of mice, the contents of muscle/gallbladder glycogen, lactate (LD), and urea nitrogen (BUN) were determined to evaluate its anti-fatigue ability. Results: The optimal extraction conditions were ethanol concentration of 70%, solvent-to-solid ratio of 1:30 g/mL, extraction temperature of 70 ℃, and extraction time of 40 min, with a GARS content of 107.85 mg/g. GARS showed significant antioxidant and anti-fatigue activities, with its antioxidant and reducing power being positively correlated with its concentration. GARS significantly prolonged the swimming and climbing times of mice (P

Abstract Background Whether iron intake can affect cardiovascular disease (CVD) and dyslipidemia is controversial. However, few studies have focused on reducing the risk of CVD in people at risk for dyslipidemia. This study explored the linear relationship and possible nonlinear relationship between CVD and dyslipidemia. Methods Dietary data were obtained from the China Health and Nutrition Survey between 2004 and 2015. The survey included 8173 participants older than 18 years. CVD risk was estimated by the Framingham risk score (FRS). Logistic regression analysis was used to determine whether iron intake affects CVD incidence and lipid profiles. The nonlinear association was tested with restricted cubic splines (RCSs). Results For males, higher total iron intake [the fifth quintile (Q) vs. Q1 odds ratio (OR): 0.335, 95% confidence interval (CI): 0.248–0.453], heme iron intake (OR: 0.679, 95% CI: 0.492–0.937) and non-heme iron intake (OR: 0.362, 95% CI: 0.266–0.492) reduced CVD incidence. Heme iron intake increased high low-density lipoprotein cholesterol (LDL-C) (OR: 1.786, 95% CI: 1.226–2.602), high total cholesterol (TC) (OR: 2.404, 95% CI: 1.575–3.669), high triglyceride (TG) (OR: 1.895, 95% CI: 1.423–2.523), and low apolipoprotein A1/apolipoprotein B (ApoA-1/ApoB) risk (OR: 1.514, 95% CI: 1.178–1.945). Moderate non-heme iron intake reduced high-density lipoprotein cholesterol (HDL-C) incidence (Q5 vs. Q1 OR: 0.704, 95% CI: 0.507–0.979). For females, higher total iron intake (Q5 vs. Q1 OR: 0.362, 95% CI: 0.266–0.492) and non-heme iron intake (OR: 0.347, 95% CI: 0.154–0.781) reduced CVD incidence. Heme iron intake increased high LDL-C (OR: 1.587, 95% CI: 1.160–2.170) and high TC incidence (OR: 1.655, 95% CI: 1.187–2.309). Conclusions Men, especially those at risk of developing dyslipidemia, should consume non-heme rather than heme iron to reduce CVD incidence. For women, increased heme iron intake did not reduce CVD incidence. Therefore, women should minimize their heme iron intake to prevent dyslipidemia.

The radial-additive friction stir repairing (R-AFSR) process was used to successfully repair the exceeded tolerance hole of 2024-T4 aluminum alloy, and the formation and tensile strength of repaired joint were investigated. The enhanced hybridizing grey wolf optimization algorithm (EHGWOA) was innovatively proposed and had the advantages of strong search ability and large convergence speed. The weights and thresholds of back propagation neural network (BPNN) were optimized by the EHGWOA to enhance its prediction accuracy. Then, the EHGWOA-BPNN system was used to predict the joint strength and optimize the process parameters combination of R-AFSR process. The results showed that the repaired joint had not only the stir zone (SZ) with the thickness almost equal to the plate thickness but also no kissing bond defect in the SZ, thereby leading to the high tensile strength of the repaired joint. The maximum tensile strength of 308 MPa was obtained under the process parameters optimized by the EHGWOA-BPNN system, which was 4.5% higher than the maximum strength before optimization. The R-AFSR has great prospects to repair the exceeded tolerance holes of aluminum alloys, and the EHGWOA-BPNN system can be used to maximize the strength of repaired joint.

Background: One common environmental stressor in fisheries is hypoxia stress, which frequently causes significant fish mortality and financial losses. This study aimed to examine the potential utility of serum concentrations of hypoxia-inducible factor-1α (HIF-1α) as a biomarker in fat greenlings, Hexagrammos otakii, under hypoxic stress. Methods: The phylogenetic analysis of HIF-1α was carried out. Then, fat greenlings (Hexagrammous otakii) were subjected to hypoxia (DO: 2.2 ± 0.2 mg/L) for 6 h, 12 h, 24 h, 48 h. Upon admission under hypoxia stress, serum HIF-1α concentrations were measured using an enzyme-linked immunosorbent assay (ELISA). The outcomes of the laboratory tests were collected. Then, correlation analysis and regression equation fitting were performed. Results: In this study, HoHIF-1α was determined by bioinformatics analysis. The relative expression of hemoglobinβ2 (HBβ2), lactate dehydrogenase (LDH), endoplasmic reticulum oxidase-1α (ERO-1α), and HIF-1α and the level of HB, LA, ERO-1α and HIF-1α were increased significantly. The hypoxia stress group had considerably greater serum HIF-1α concentrations in comparison to the control group. Furthermore, compared to lactate concentrations, HIF-1α concentrations were linked to a superior predictive capacity for hypoxia stress diagnosis. Then, the correlation analysis result showed that HIF-1α was positively correlated with hemoglobin (HB), ERO-1α, and lactic acid (LA). Meanwhile, HIF-1α has a good linear relationship with HB, ERO-1α, and LA respectively. The HIF-1α concentrations increase of more than 30.27 pg/mL indicates severe hypoxia stress in the H. otakii. Conclusions: HIF-1α was positively correlated with HB, ERO-1α, and LA in H. otakii under hypoxia stress. Serum HIF-1α concentrations are a valuable indicator for hypoxia stress diagnosis and H. otakii recovery status prediction.

Atmospheric fine particulate matter (PM2.5) can harm various systems in the human body. Due to limitations in the current understanding of epidemiology and toxicology, the disease types and pathogenic mechanisms induced by PM2.5 in various human systems remain unclear. In this study, the disease types induced by PM2.5 in the respiratory, circulatory, endocrine, and female and male urogenital systems have been investigated and the pathogenic mechanisms identified at molecular level. The results reveal that PM2.5 is highly likely to induce pulmonary emphysema, reperfusion injury, malignant thyroid neoplasm, ovarian endometriosis, and nephritis in each of the above systems respectively. The most important co-existing gene, cellular component, biological process, molecular function, and pathway in the five systems targeted by PM2.5 are Fos proto-oncogene (FOS), extracellular matrix, urogenital system development, extracellular matrix structural constituent conferring tensile strength, and ferroptosis respectively. Differentially expressed genes that are significantly and uniquely targeted by PM2.5 in each system are BTG2 (respiratory), BIRC5 (circulatory), NFE2L2 (endocrine), TBK1 (female urogenital) and STAT1 (male urogenital). Important disease-related cellular components, biological processes, and molecular functions are specifically induced by PM2.5. For example, response to wounding, blood vessel morphogenesis, body morphogenesis, negative regulation of response to endoplasmic reticulum stress, and response to type I interferon are the top uniquely existing biological processes in each system respectively. PM2.5 mainly acts on key disease-related pathways such as the PD-L1 expression and PD-1 checkpoint pathway in cancer (respiratory), cell cycle (circulatory), apoptosis (endocrine), antigen processing and presentation (female urogenital), and neuroactive ligand-receptor interaction (male urogenital). This study provides a novel analysis strategy for elucidating PM2.5-related disease types and is an important supplement to epidemiological investigation. It clarifies the risks of PM2.5 exposure, elucidates the pathogenic mechanisms, and provides scientific support for promoting the precise prevention and treatment of PM2.5-related diseases.

Active front-end converters are part of high power installations for regenerative energy systems, feeding the regenerated energy into the utility. Under the island mode operation of the regenerative energy system, the load characteristics are difficult to detect, and the change of the load characteristics will cause the corresponding resonance. V/f control is usually used to ensure the harmonic quality. At high switching frequency, it has a good control effect. However, high switching frequency causes high switching loss. In order to reduce the switching loss, it will produce more harmonic distortion. Furthermore, the commonly used modulation strategies in this case face the problem of low real-time performance. Therefore, in order to avoid the harm caused by circuit resonance under the condition of reducing the switching frequency, this paper proposes a specific harmonic suppression algorithm with high real-time performance, which can be used as an optional control algorithm in the island operation state of power system. At the same time, aiming at the difficulty of adjusting the weight factors, this paper proposes a weight factor automatic tuner, which automatically adjusts the weight factors according to the harmonic component.

Nuclear progesterone receptor (nPR) is a member of the nuclear receptor family known to play a critical role in gonad development, gametogenesis, and ovulation in vertebrates, and also important in pregnancy maintenance and parturition in mammals. However, its biological functions in ovoviviparity teleosts are less clear. This study aimed to determine the possible role of nPR in fish oogenesis, pregnancy and parturition using black rockfish as a model. The npr, which consists of 2076 bp and codes for a 691 amino acids protein, was cloned. Phylogenetic analysis revealed that the nPR of black rockfish is more conserved in teleosts. Quantitative real-time PCR analyses in various tissues showed that npr was mainly detected in the pituitary followed by the ovary, testis and brain, while it was very low or undetectable in the spleen, head kidney, intestine and gill. During the gonadal development process, the npr level showed no variation in the ovary. In testis, the mRNA level of npr showed varied expression in different developmental stages with the highest level in the maturation stage. Detection of npr expression during fertilization and the perinatal period further showed that nPR may play important roles in the regulation of pregnancy and the parturition. In situ hybridization further revealed that npr mRNA was observed in the follicular cell layer during the perinatal period. The results from in vitro experiments showed that npr level was significantly downregulated when the primary cultured follicular cells during vitellogenesis (stage Ⅳ) were exposed to hCG. Studies using primary culture of black rockfish ovarian cells during the perinatal period, treated in vitro revealed that genes related to PGs synthesis (pla2g4a, cox2) and matrix metalloproteinases (mmp2, mmp9) were upregulated in response to 17,20β-P. However, treatment with 17,20β-P downregulated npr expression. In conclusion, these data suggest that nPR plays an essential role in fertilization, pregnancy maintenance and parturition in black rockfish.

Abstract The mechanochemical GTPase dynamin-related protein 1 (Drp1) catalyzes mitochondrial and peroxisomal fission, but the regulatory mechanisms remain ambiguous. Here we find that a conserved, intrinsically disordered, six-residue Short Linear Motif at the extreme Drp1 C-terminus, named CT-SLiM, constitutes a critical allosteric site that controls Drp1 structure and function in vitro and in vivo. Extension of the CT-SLiM by non-native residues, or its interaction with the protein partner GIPC-1, constrains Drp1 subunit conformational dynamics, alters self-assembly properties, and limits cooperative GTP hydrolysis, surprisingly leading to the fission of model membranes in vitro. In vivo, the involvement of the native CT-SLiM is critical for productive mitochondrial and peroxisomal fission, as both deletion and non-native extension of the CT-SLiM severely impair their progression. Thus, contrary to prevailing models, Drp1-catalyzed membrane fission relies on allosteric communication mediated by the CT-SLiM, deceleration of GTPase activity, and coupled changes in subunit architecture and assembly-disassembly dynamics.

Abstract Background The association between lipid and bone metabolism, particularly the role of high-density lipoprotein cholesterol (HDL-C) in regulating bone mineral density (BMD), is of significant interest. Despite numerous studies, findings on this relationship remain inconclusive, especially since evidence from large, sexually diverse Chinese populations is sparse. This study, therefore, investigates the correlation between HDL-C and lumbar BMD in people of different genders using extensive population-based data from physical examinations conducted in China. Methods Data from a cross-sectional survey involving 20,351 individuals aged > = 20 years drawn from medical records of health check-ups at the Health Management Centre of the Henan Provincial People’s Hospital formed the basis of this study. The primary objective was to determine the correlation between HDL-C levels and lumbar BMD across genders. The analysis methodology included demographic data analysis, one-way ANOVA, subgroup analyses, multifactorial regression equations, smoothed curve fitting, and threshold and saturation effect analyses. Results Multifactorial regression analysis revealed a significant inverse relationship between HDL-C levels and lumbar BMD in both sexes, controlling for potential confounders (Male: β = -8.77, 95% CI -11.65 to -5.88, P 28 kg/m2 and HDL-C > 1.45 mmol/L and in females with a BMI between 24 and 28 kg/m2. Conclusion Elevated HDL-C is associated with decreased bone mass, particularly in obese males. These findings indicate that individuals with high HDL-C levels should receive careful clinical monitoring to mitigate osteoporosis risk. Trial registration The research protocol received ethics approval from the Ethics Committee at Beijing Jishuitan Hospital, in conformity with the Declaration of Helsinki guidelines (No. 2015-12-02). These data are a contribution of the China Health Quantitative CT Big Data Research team, registered at clinicaltrials.gov (code: NCT03699228).

Abstract Metastasis is the leading cause of high mortality in colorectal cancer (CRC), which is not only driven by changes occurring within the tumor cells, but is also influenced by the dynamic interaction between cancer cells and components in the tumor microenvironment (TME). Currently, the exploration of TME remodeling and its impact on CRC metastasis has attracted increasing attention owing to its potential to uncover novel therapeutic avenues. Noteworthy, emerging studies suggested that tumor-associated macrophages (TAMs) within the TME played important roles in CRC metastasis by secreting a variety of cytokines, chemokines, growth factors and proteases. Moreover, TAMs are often associated with poor prognosis and drug resistance, making them promising targets for CRC therapy. Given the prognostic and clinical value of TAMs, this review provides an updated overview on the origin, polarization and function of TAMs, and discusses the mechanisms by which TAMs promote the metastatic cascade of CRC. Potential TAM-targeting techniques for personalized theranostics of metastatic CRC are emphasized. Finally, future perspectives and challenges for translational applications of TAMs in CRC development and metastasis are proposed to help develop novel TAM-based strategies for CRC precision medicine and holistic healthcare.

Abstract Background Antiviral therapy has been reported to be associated with lower recurrence rate of hepatocellular carcinoma (HCC) for patients with hepatitis B virus (HBV) infection. While entecavir (ETV) and tenofovir disoproxil fumarate (TDF) were both recommended as first-line therapies for HBV patients, recent retrospective studies proposed a lower incidence rate of HCC occurrence or recurrence in those receiving TDF compared ETV. However, the survival benefits of switching to TDF therapy after prolonged ETV treatment before surgery remain uncertain. We delineate the rationale and design of SWITE, a randomized, open-label, phase III trial contrasting TDF switch therapy versus ETV maintenance in HBV-related HCC patients. Methods and analysis This is a prospective, randomized, controlled, single-center study with two parallel groups of patients with HBV-related HCC who have received long-term ETV therapy before surgery. West China Hospital will enroll 238 patients, randomized in a 1:1 ratio to TDF switch therapy or ETV maintenance after surgery. The primary endpoint of this study is 3-year recurrence free survival (RFS), with the secondary endpoint being 3-year overall survival (OS) after curative surgery of HCC. Safety events will be diligently recorded. Ethics and dissemination The study protocol aligns with the ethical guidelines of the 1975 Declaration of Helsinki. It was approved by ethics committee of West China Hospital (approval number: 2022-074) and was registered with chictr.org.cn (chiCTR2200057867). Informed consent will be obtained from all participants. The results of this trial will be published in peer-reviewed journals and presentations at national and international conferences relevant to this topic. Trial registration chiCTR2200057867 . Date of registration is March 20 2022.

This study presents a bionic structure-based liquid cooling plate designed to address the heat generation characteristics of prismatic lithium-ion batteries. The size of the lithium-ion battery is 148 mm × 26 mm × 97 mm, the positive pole size is 20 mm × 20 mm × 3 mm, and the negative pole size is 22 mm × 20 mm × 3 mm. Experimental testing of the Li-ion battery’s heat generation model parameters, in conjunction with bionic structure and micro-channel features, has led to the development of this innovative cooling system. The traditional bionic liquid cooling plate’s structure is often singular; however, the flow path of the liquid cooling plate designed in this paper is based on the combination of the distribution of human blood vessel branches and the structure of insect wing veins. The external dimension of the liquid cooling plate is 152 mm × 100 mm × 6 mm (length × width × height). Utilizing numerical simulation and thermodynamic principles, we analyzed the heat transfer efficacy of the bionic liquid cooling module for power batteries. Specifically, we investigated the impact of varying coolant flow rates and the contact radius between flow channels on the thermal performance of the bionic battery modules. Our findings indicate that a liquid flow rate of 0.6 m/s achieves a stable maximum surface temperature and temperature differential across the bionic battery liquid cooling module, with a relatively low overall system power consumption, suggesting room for further enhancement of heat transfer performance. By augmenting the contact radius between flow channels, we observed an initial increase in the maximum surface temperature, temperature differential, and inlet–outlet pressure differential at a flow rate of 0.2 m/s. However, at flow rates equal to or exceeding 0.4 m/s, these parameters stabilized across different design Scenarios. Notably, the pump power consumption remained consistent across various scenarios and flow rates. This study’s outcomes offer valuable insights for the development of liquid-cooled battery thermal management systems that are energy-efficient and offer superior heat transfer capabilities.

The identification of drug–target interaction (DTI) is crucial for drug discovery. However, how to reduce the graph neural network’s false positives due to its bias and negative transfer in the original bipartite graph remains to be clarified. Considering that the impact of heterogeneous auxiliary information on DTI varies depending on the drug and target, we established an adaptive enhanced personalized meta-knowledge transfer network named Meta Graph Association-Aware Contrastive Learning (MGACL), which can transfer personalized heterogeneous auxiliary information from different nodes and reduce data bias. Meanwhile, we propose a novel DTI association-aware contrastive learning strategy that aligns high-frequency drug representations with learned auxiliary graph representations to prevent negative transfer. Our study improves the DTI prediction performance by about 3%, evaluated by analyzing the area under the curve (AUC) and area under the precision–recall curve (AUPRC) compared with existing methods, which is more conducive to accurately identifying drug targets for the development of new drugs.

The codon usage patterns of mitochondrial genomes offer insights into the evolutionary and phylogenetic studies of species. Codon usage analysis has been conducted in a few Chironomidae species, and the codon usage patterns in other species remain ambiguous. We aim to reveal the codon usage differences in the mitochondrial genomes across this family. We sequenced the first mitochondrial genome of the genus Conchapelopia and the third mitochondrial genome of the subfamily Tanypodinae. Then, we analyzed its relative synonymous codon usage and effective number of codons with registered mitochondrial genomes from 28 other genera. The results indicated that there was limited variation in codon usage across five subfamilies, Chironominae, Orthocladiinae, Diamesinae, Prodiamesinae and Tanypodinae. While Parochlus steinenii from Podonominae presented a weaker codon bias, P. steinenii possessed the most genes experiencing natural selection. Additionally, ND1, ND2 and ND3 were found to be the most frequently selected genes across all species. Our findings contribute to further understanding the evolutionary and phylogenetic relationships of Chironomidae.

Marine microbial secondary metabolites with diversified structures have been found as promising sources of anti-inflammatory lead compounds. This review summarizes the sources, chemical structures, and pharmacological properties of anti-inflammatory natural products reported from marine microorganisms in the past three years (2021–2023). Approximately 252 anti-inflammatory compounds, including 129 new ones, were predominantly obtained from marine fungi and they are structurally divided into polyketides (51.2%), terpenoids (21.0%), alkaloids (18.7%), amides or peptides (4.8%), and steroids (4.3%). This review will shed light on the development of marine microbial secondary metabolites as potential anti-inflammatory lead compounds with promising clinical applications in human health.

As the scale of power systems continue to expand and their structure becomes increasingly complex, it is likely that branch power flow exceedance may occur during the operation of power systems, posing threats to the safe and stable operation of entire systems. This paper addresses the issue of branch flow exceedance in power networks. To enhance the operational efficiency and optimize the adjustment effects, this paper proposes a method for eliminating branch power flow exceedance by improving the particle swarm optimization (PSO) algorithm through the introduction of sensitivity and distribution factors. Firstly, it introduces the basic theory and calculation methods of sensitivity analysis, focusing on deriving the calculation principles of power flow sensitivity and voltage sensitivity, used to predict the responses of power flow at each branch in the power network to power or voltage changes. Subsequently, the paper provides a detailed derivation of the calculation principles for the line outage distribution factor (LODF), which effectively assesses the changes in branch power flow in the power network under specific conditions. Finally, a method for eliminating branch power flow exceedance based on a combination of sensitivity analysis and PSO algorithm is proposed. Through case analysis, it is demonstrated how to use the sensitivity and distribution factor to predict and control the power flow exceedance issues in power systems, verifying the efficiency and practicality of the proposed method for eliminating branch power flow exceedance. The study shows that this method can rapidly and accurately predict and address branch power flow exceedance in power system, thereby enhancing the operational safety of the power system.

IntroductionThe contamination of farmland soil with the heavy metal cadmium (Cd) has consistently been a globally recognized environmental issue, especially with the rapid development of the central part of the Hanjiang River basin. The Cd contamination has become increasingly serious, and the accumulation and translocation of Cd in the soil-crop system warrant further research.MethodsIn this study, representative yellowish-brown soil and limestone soil from Hubei Province in China, as well as five varieties of potato (Solanum tuberosum L), were selected to investigate Cd accumulation and transfer regulation from soil to plants using pot tests at varying Cd concentration levels.Results and discussionFor Eshu-12, Favorita, Huashu-6, Mira, and Zhongshu-5, the accumulation capacity of Cd in different parts exhibits a consistent pattern: Cdroot > Cdstem > Cdleaf > Cdtuber. The potato varieties exhibited distinct differences in Cd concentration, as follows: CdFavorita > CdMira > CdEshu-12 > CdHuashu-6 > CdZhongshu-5. The yellowish-brown soil demonstrated a higher accumulation and lower transport capacity to the plants of Cd, while limestone soil exhibited the opposite trend. The bio-concentration factor and transfer coefficients in yellowish-brown soil revealed significant (p

Objective: We explored the differences in deep venous catheterization-associated complications between patients with hematological malignancies after peripherally inserted central catheter placement and such patients after implantable venous access port catheterization. Introduction: peripherally inserted central catheters and implantable venous access ports are the most popular devices used for chemotherapy. However, no study has revealed differences between peripherally inserted central catheters and implantable venous access ports in Chinese patients with hematological malignancies. Methods: The clinical data of 322 patients with hematological malignancies who were treated from January 1, 2020 to December 30, 2021 were included in a retrospective cohort study. Postoperative color Doppler ultrasonography and follow-up results were used to compare the incidence rates of deep venous catheterization -associated complications after peripherally inserted central catheters and implantable venous access ports catheterization. Results: The relative risk of catheter-related complications considering the type of device was 8.3 (95% CI = 3.0–22.8). In addition, chi-square segmentation analysis revealed a significant difference in the complication rate between the internal jugular vein and the basilic vein (χ 2 = 22.002, p

The aim of this study was to investigate the effects and mechanisms of action of extract of Adventitious Root of Ginseng (GARE) on a mouse model of Type 1 diabetes mellitus (T1DM). Firstly, using network pharmacology methods to predict relevant targets. The main active components of GARE were analyzed using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS). Mice were then divided into multiple experimental groups and a T1DM model was established. The results showed that GARE significantly reduced blood glucose levels in mice, while also decreasing the levels of total cholesterol (TC), triglycerides (TG), and glycosylated hemoglobin (GHb). GARE increased the activity of antioxidant enzymes and reduced the expression of inflammatory factors in the liver. Furthermore, GARE exerted its protective effects by inhibiting the PI3K/AKT/mTOR signaling pathway. These findings suggest that GARE may have potential therapeutic effects for T1DM and provide a theoretical basis for the development and utilization of adventitious root of ginseng (GAR) resources.

Tick-borne Apicomplexan parasites pose a significant threat to both public health and animal husbandry. Identifying potential pathogenic parasites and gathering their epidemiological data are essential for prospectively preventing and controlling infections. In the present study, genomic DNA of ticks collected from two goat flocks (Goatflock1 and Goatflock2) and one dog group (Doggroup) were extracted and the 18S rRNA gene of Babesia/Theileria/Colpodella spp. was amplified by PCR and sequenced. Phylogenetic analysis was conducted based on the obtained sequences. The differences in pathogen positive rates between ticks of different groups were statistically analyzed using the Chi-square or continuity-adjusted Chi-square test. As a result, two pathogenic Theileria (T.) luwenshuni genotypes, one novel pathogenic Colpodella sp. HLJ genotype, and two potential novel Colpodella spp. (referred to as Colpodella sp. struthionis and Colpodella sp. yiyuansis in this study) were identified in the Haemaphysalis (H.) longicornis ticks. Ticks of Goatflock2 had a significantly higher positive rate of Colpodella spp. than those from Goatflock1 (χ2=92.10; P = 8.2 × 10−22) and Doggroup (χ2=42.34; P = 7.7 × 10−11), and a significantly higher positive rate of T. luwenshuni than Doggroup (χ2=5.38; P = 0.02). However, the positive rates of T. luwenshuni between Goatflock1 and Goatflock2 were not significantly different (χ2=2.02; P = 0.16), and so as the positive rates of both pathogens between Goatflock1 and Doggroup groups (P > 0.05). For either Colpodella spp. or T. luwenshuni, no significant difference was found in prevalence between male and female ticks. These findings underscore the potential importance of Colpodella spp. in domestic animal-attached ticks, as our study revealed two novel Colpodella spp. and identified Colpodella spp. in H. longicornis for the first time. The study also sheds light on goats' potential roles in the transmission of Colpodella spp. to ticks and provides crucial epidemiological data of pathogenic Theileria and Colpodella. These data may help physicians, veterinarians, and public health officers prepare suitable detection and treatment methods and develop prevention and control strategies.

Abstract The North Pacific sea surface temperature (SST) has a profound climatic influence. The El Niño‐Southern Oscillation (ENSO) significantly impacts the North Pacific SST; however, the influence of the distinct phases of ENSO on SST predictability remains unclear. To overcome the model limitations, this study assessed SST predictability under diverse ENSO phases using reanalysis. The predictability limit of the North Pacific SST under La Niña (8.4 months) is longer than that under Neutral (5.9 months) and El Niño (5.5 months) conditions, which unveils asymmetry. This asymmetry mirrors contemporary multimodal prediction skills. Error growth dynamics reveal La Niña's robust signal strength with a slow error growth rate, in contrast to El Niño's weaker signal and faster error growth. There exhibits intermediate signal strength and elevated error growth in Neutral condition. Physically, predictability signal strength aligns with SST variability, whereas the error growth rate correlates with atmospheric‐ocean heating anomalies. La Niña, which induces positive heating anomalies, minimizes the impact of atmospheric noise, resulting in lower error growth. The result is beneficial for improving North Pacific SST predictions.

Purpose Parent involvement is crucial for tailored early intervention programs. The Hanen More Than Words (HMTW) program is a parent-implemented language intervention for autistic children. The current study examined the effectiveness of the HMTW program delivered online among Chinese families. Methods Using a randomized controlled trial design, 22 Chinese families of autistic children in Hong Kong completed the trial. Baseline and post-intervention assessments were conducted to measure changes in parent-child interaction, parents’ use of linguistic facilitation techniques (LFTs), and children's communication skills. Additionally, the influence of parental self-efficacy and parenting stress on treatment outcomes was explored. Results The intervention group demonstrated significant improvements in parent-child attention synchrony. Although the treatment effect on children's spontaneous communication was not significant, the intervention group showed a larger effect size compared to the controls. The treatment outcomes were mainly influenced by the parents’ initial levels of self-efficacy but not by parenting stress. Conclusion These findings provide preliminary evidence of the effectiveness of the online-delivered HMTW program for Chinese parents of autistic children. Further research involving a larger sample and focusing on long-term effects is needed.

Hepatocellular carcinoma (HCC) is a common malignancy with poor prognosis. In recent years, immune checkpoint inhibitors (ICIs) have enabled breakthroughs in the clinical treatment of patients with HCC, but the overall response rate to ICIs in HCC patients is still low, and no validated biomarker is available to guide clinical decision making. Here, we demonstrated that the long non-coding RNA Lnc-CCNH-8 is highly expressed in HCC and correlates with poor prognosis. Functionally, elevated Lnc-CCNH-8 inactivated co-cultured T cells in vitro and compromised antitumor immunity in an immunocompetent mouse model. Mechanistically, up-regulated Lnc-CCNH-8 can sponge microRNA (miR)-217 to regulate the expression of PD-L1. In addition, Lnc-CCNH-8 can also stabilize PD-L1 through miR-3173/PKP3 axis. Furthermore, mice bearing tumors with high Lnc-CCNH-8 expression had significant therapeutic sensitivity to anti-PD-L1 monoclonal antibody treatment. More important, HCC patients with high levels of plasma exosomal Lnc-CCNH-8 had a better therapeutic response to ICIs. Taken together, our results reveal the function of Lnc-CCNH-8 in inducing immune escape from CD8+ T-cell-mediated killing by up-regulating PD-L1 in a miR-217/miR-3173-dependent manner, which also reveals a novel mechanism of PD-L1 regulation in HCC, and exosomal Lnc-CCNH-8 can serve as a predictive marker for immunotherapy response in HCC.

Abstract Background The impact of total cholesterol (TC) on lumbar bone mineral density (BMD) is a topic of interest. However, empirical evidence on this association from demographic surveys conducted in China is lacking. Therefore, this study aimed to examine the relationship between serum TC and lumbar BMD in a sample of 20,544 Chinese adults between the ages of 20 and 80 years over a period of 5 years, from February 2018 to February 2023. Thus, we investigated the effect of serum TC level on lumbar BMD and its relationship with bone reduction in a Chinese adult population. Methods This cross-sectional study used data obtained from the Department of Health Management at Henan Provincial People’s Hospital between February 2018 and February 2023. The aim of this study was to examine the correlation between serum TC and lumbar BMD in individuals of different sexes. The research methodology encompassed population description, analysis of stratification, single-factor and multiple-equation regression analyses, smooth curve fitting, and analysis of threshold and saturation effects. The R and EmpowerStats software packages were used for statistical analysis. Results After adjusting for confounding variables, a multiple linear regression model revealed a significant correlation between TC and lumbar BMD in men. In subgroup analysis, serum TC was found to have a positive association with lumbar BMD in men, specifically those aged 45 years or older, with a body mass index (BMI) ranging from 24 to 28 kg/m2. A U-shaped correlation arose between serum TC and lumbar BMD was detected in women of different ages and BMI, the inflection point was 4.27 mmol/L for women aged ≥ 45 years and 4.35 mmol/L for women with a BMI of ≥ 28 kg/m2. Conclusion In this study, Chinese adults aged 20–80 years displayed different effects of serum TC on lumbar BMD in sex-specific populations. Therefore, monitoring BMI and serum TC levels in women of different ages could prevent osteoporosis and osteopenia. Trial registration The research protocol was approved by the Ethics Committee of Beijing Jishuitan Hospital, in accordance with the Declaration of Helsinki guidelines (No. 2015-12-02). These data are part of the China Health Quantitative CT Big Data Research team, which has been registered at clinicaltrials.gov (code: NCT03699228).

Abstract T cell leukemia homeobox 2 (TLX2) plays an important role in some tumors. Bioinformatics and experimental validation represent a useful way to explore the mechanisms and functions of TLX2 gene in the cancer disease process from a pan cancer perspective. TLX2 was aberrantly expressed in pan cancer and cell lines and correlated with clinical stage. High TLX2 expression was significantly associated with poor overall survival in COAD, KIRC, OC, and UCS. The greatest frequency of TLX2 alterations in pan cancer was amplification. Alterations of NXF2B, MSLNL, PCGF1, INO80B-WBP1, LBX2-AS1, MRPL53, LBX2, TTC31, WDR54, and WBP1 co-occurred in the TLX2 alteration group. PFS was significantly shorter in the TLX2-altered group (n = 6) compared to the TLX2-unaltered group (n = 400). Methylation levels of TLX2 were high in 17 tumors. TLX2 expression was associated with MSI in seven tumors and TMB in five tumors. TLX2 expression was associated with immune infiltration and immune checkpoint genes. TLX2 may be associated with some pathways and chemoresistance. We constructed a possible competing endogenous RNA (ceRNA) network of LINC01010/miR-146a-5p/TLX2 in OC. TLX2 expression was significantly upregulated in ovarian cancer cell lines compared to ovarian epithelial cell lines. Aberrant expression of TLX2 in pan cancer may promote tumorigenesis and progression through different mechanisms. TLX2 may represent an important therapeutic target for human cancers.

Abstract Background Social frailty has not been comprehensively studied in China. Our objective is to investigate the prevalence of social frailty among the older population in China, as well as identify relevant factors and urban-rural differences. Methods We obtained data from the Fourth Sample Survey of the Aged Population in Urban and Rural China (SSAPUR) database. The study employed a multistage, stratified, cluster-sampling method, recruiting a total of 224,142 adults aged 60 years or older. Participants were interviewed to gather demographic data and information on family, health and medical conditions, health care service status, living environment conditions, social participation, protected rights status, spiritual and cultural life, and health. Social frailty was assessed using the HALFE Social Frailty Index. A score of three or above indicated social frailty. Results We analyzed a total of 222,179 cases, and the overall prevalence of social frailty was found to be 15.2%. The highest prevalence was observed among participants aged 75–79 years (18.0%). The prevalence of social frailty was higher in rural older populations compared to urban older populations (19.9% in rural vs. 10.9% in urban, P

Methionine oxidation to the sulfoxide form (MSox) is a poorly understood post-translational modification of proteins associated with non-specific chemical oxidation from reactive oxygen species (ROS), whose chemistries are linked to various disease pathologies, including neurodegeneration. Emerging evidence shows MSox site occupancy is, in some cases, under enzymatic regulatory control, mediating cellular signaling, including phosphorylation and/or calcium signaling, and raising questions as to the speciation and functional nature of MSox across the proteome. The 5XFAD lineage of the C57BL/6 mouse has well-defined Alzheimer’s and aging states. Using this model, we analyzed age-, sex-, and disease-dependent MSox speciation in the mouse hippocampus. In addition, we explored the chemical stability and statistical variance of oxidized peptide signals to understand the needed power for MSox-based proteome studies. Our results identify mitochondrial and glycolytic pathway targets with increases in MSox with age as well as neuroinflammatory targets accumulating MSox with AD in proteome studies of the mouse hippocampus. Further, this paper establishes a foundation for reproducible and rigorous experimental MSox-omics appropriate for novel target identification in biological discovery and for biomarker analysis in ROS and other oxidation-linked diseases.

The complete mitochondrial genome of Polypedilum henicurum was sequenced and analyzed. The whole mitogenome is 15,964 bp in length and contains 13 protein-coding genes (PCGs), 22 transfer RNAs (tRNAs), and two ribosomal RNAs (rRNAs). The overall nucleotide composition is 39.5% A, 39.0% T, 13.1% C, and 8.4% G. Most PCGs start with ATN codon excluding COX1 (TTG) and all PCGs end with TAA codon. Gene arrangement stays the same with the ancestral mitochondrial genome. Bayesian inference phylogenetic tree supports its close relationship with P. unifascium. This work enriches the library of Chironomidae mitochondrial genomes and provides a valuable resource for understanding the evolutionary history of Polypedilum.

Abstract Background Diabetes and hyperlipidaemia are both risk factors for coronary artery disease, and both are associated with a high triglyceride-glucose index (TyG index). The TyG index has been presented as a marker of insulin resistance (IR). Its utility in predicting and detecting cardiovascular disease has been reported. However, few studies have found it to be a helpful marker of atherosclerosis in patients with symptomatic coronary artery disease (CAD). The purpose of this study was to demonstrate that the TyG index can serve as a valuable marker for predicting coronary and carotid atherosclerosis in symptomatic CAD patients, regardless of diabetes mellitus and hyperlipidaemia. Methods This study included 1516 patients with symptomatic CAD who underwent both coronary artery angiography and carotid Doppler ultrasound in the Department of Cardiology at Tianjin Union Medical Center from January 2016 to December 2022. The TyG index was determined using the Ln formula. The population was further grouped and analysed according to the presence or absence of diabetes and hyperlipidaemia. The Gensini score and carotid intima-media thickness were calculated or measured, and the patients were divided into four groups according to TyG index quartile to examine the relationship between the TyG index and coronary or carotid artery lesions in symptomatic CAD patients. Results In symptomatic CAD patients, the TyG index showed a significant positive correlation with both coronary lesions and carotid plaques. After adjusting for sex, age, smoking, BMI, hypertension, diabetes, and the use of antilipemic and antidiabetic agents, the risk of developing coronary lesions and carotid plaques increased across the baseline TyG index. Compared with the lowest quartile of the TyG index, the highest quartile (quartile 4) was associated with a greater incidence of coronary heart disease [OR = 2.55 (95% CI 1.61, 4.03)] and carotid atherosclerotic plaque [OR = 2.31 (95% CI 1.27, 4.20)] (P

Abstract Background Breast cancer‐related lymphedema (BCRL) is one of the common postoperative complications that severely affects the functions of the arm and quality of life. Since lymphedema is difficult to treat and prone to recurrence, early prevention of lymphedema is crucial. Methods Patient diagnosed with breast cancer (N = 108) were randomized to the intervention (n = 52) or control group (n = 56). In the intervention group, patients were provided the lymphedema prevention program based on the theory of knowledge–attitude–practice during the perioperative period and the first three chemotherapy sessions (mainly includes health education, seminars, knowledge manuals, sports guidance, peer education, and WeChat group).The limb volume, handgrip strength, arm function, and quality of life were measured in all patients at the baseline, 9 weeks (T1), and 18 weeks (T2) after surgery. Results The incidence of lymphedema in the Intervention group was numerically lower than in the control group after implementing the lymphedema prevention program, but the difference was not statistically significant (T1: 1.9% vs. 3.8%, p = 1.000; T2: 3.6% vs. 7.1%, p = 0.744). However, compared with the control group, the intervention group showed there was less deterioration in handgrip strength (T1 [t = −2.512, p

Objective The sagittal shapes of the femoral condyles were thought to consist of circles. However, the line connecting the centers of circles was not consistent with the surgical epicondylar axis (SEA) which was commonly used in surgery. Recently, ellipses have been proposed as an alternative method to represent the sagittal femoral condylar shape. Does the condylar ellipse line (CEL) coincide with the SEA in 3D MRI reconstruction analysis? Methods From May to August 2021, a total of 80 healthy subjects were scanned by MRI on the right knee in this retrospective study. The ellipses on the most distal slices of the medial and lateral condyles were determined. A line connecting the centers of the medial and lateral ellipses was the CEL. A line connecting the deepest point of the medial sulcus and the most prominent point of the lateral epicondyle was the SEA. Angular measurement of the SEA and the CEL relative to the posterior condylar line (PCL) and the distal condylar line (DCL) was performed on an axial and coronal view of the 3D model, respectively. Measurements were compared between males and females by using the independent‐samples t‐test. Pearson correlation was used to analyze the relationship between SEA‐PCL and CEL‐PCL, SEA‐DCL, and CEL‐DCL. Results On the axial view, the mean SEA‐CEL was 0.35° ± 0.96°. SEA‐PCL (2.91° ± 1.40°) had a high correlation with CEL‐PCL (3.27° ± 1.11°) (r = 0.731, p

Abstract The aim of this study was to investigate the possible interaction of mitochondrial dysfunction and inflammatory cytokines in the risk of anxiety and depression. We utilized the UK Biobank for the sample of this study. A mitochondria-wide association(MiWAS) and interaction analysis was performed to investigate the interaction effects of mitochondrial DNA (mtDNA)×C-reactive protein (CRP) on the risks of self-reported anxiety (N = 72,476), general anxiety disorder (GAD-7) scores (N = 80,853), self-reported depression (N = 80,778), Patient Health Questionnaire (PHQ-9) scores (N = 80,520) in total samples, females and males, respectively, adjusting for sex, age, Townsend deprivation index (TDI), education score, alcohol intake, smoking and 10 principal components. In all, 25 mtSNPs and 10 mtSNPs showed significant level of association with self-reported anxiety and GAD-7 score respectively. A total of seven significant mtDNA × CRP interactions were found for anxiety, such as m.3915G>A(MT-ND1) for self-reported anxiety in total subjects (P = 6.59 × 10−3), m.4561T>C(MT-ND2) (P = 3.04 × 10−3) for GAD-7 score in total subjects. For depression, MiWAS identified 17 significant mtSNPs for self-reported depression and 14 significant mtSNPs for PHQ-9 scores. 17 significant mtDNA associations (2 for self-reported depression and 15 for PHQ-9 score) was identified, such as m.14869G>A(MT-CYB; P = 2.22 × 10−3) associated with self-reported depression and m.4561T>C (MT-ND2; P value = 3.02 × 10−8) associated with PHQ-9 score in all subjects. In addition, 5 common mtDNA shared with anxiety and depression were found in MiWAS, and 4 common mtDNA variants were detected to interact with CRP for anxiety and depression, such as m.9899T>C(MT-CO3). Our study suggests the important interaction effects of mitochondrial function and CRP on the risks of anxiety and depression.

Abstract Objectives Eicosapentaenoic acid in its ethyl ester form is the single active component of icosapent ethyl (IPE). This study was a phase III, multi-center trial assessing the safety and efficiency of IPE for treating very high triglyceride (TG) in a Chinese cohort. Methods Patients having TG levels (5.6–22.6 mmol/L) were enrolled and randomly assigned to receive a treatment of oral intake of 4 g or 2 g/day of IPE, or placebo. Before and after 12 weeks of treatment, TG levels were assessed and the median was calculated to determine the change between the baseline and week 12. In addition to examining TG levels, the impact of such treatments on other lipid changes was also investigated. The official Drug Clinical Trial Information Management Platform has registered this study (CTR20170362). Results Random assignments were performed on 373 patients (mean age 48.9 years; 75.1% male). IPE (4 g/day) lowered TG levels by an average of 28.4% from baseline and by an average of 19.9% after correction for placebo (95% CI: 29.8%-10.0%, P