Search

Objective To determine the efficacy and safety of Astragalus combined with renin-angiotensin-aldosterone system (RAAS) blockers in treating stage III diabetic nephropathy (DN) by meta-analysis.Methods PubMed, Embase, Cochrane Library, Wiley, and Web of Science databases were searched for articles published between August 2007 and August 2022. Clinical studies on Astragalus combined with RAAS blockers for the treatment of stage III DN were included. Meta-analysis was performed by RevMan 5.1 and Stata 14.3 software.Results A total of 32 papers were included in this meta-analysis, containing 2462 patients from randomized controlled trials, with 1244 receiving the combination treatment and 1218 solely receiving RAAS blockers. Astragalus combined with RAAS blockers yielded a significantly higher total effective rate (TER) (mean difference [MD] 3.63, 95% confidence interval [CI] 2.59–5.09) and significantly reduced urinary protein excretion rate (UPER), serum creatinine (Scr), blood urine nitrogen (BUN) and glycosylated hemoglobin (HbAlc) levels. In subgroup analysis, combining astragalus and angiotensin receptor blocker significantly lowered fasting plasma glucose (FPG) and 24 h urinary protein (24hUTP) levels, compared with the combined astragalus and angiotensin-converting enzyme inhibitor treatment. Meanwhile, the latter significantly decreased the urinary microprotein (β2-MG). Importantly, the sensitivity analysis confirmed the study’s stability, and publication bias was not detected for UPER, BUN, HbAlc, FPG, or β2-MG. However, the TER, SCr, and 24hUTP results suggested possible publication bias.Conclusions The astragalus-RAAS blocker combination treatment is safe and improves outcomes; however, rigorous randomized, large-scale, multi-center, double-blind trials are needed to evaluate its efficacy and safety in stage III DN.

The discovery of promising cytokines and clarification of their immunological mechanisms in controlling the intracellular fate of Mycobacterium tuberculosis (Mtb) are necessary to identify effective diagnostic biomarkers and therapeutic targets. To escape immune clearance, Mtb can manipulate and inhibit the normal host process of phagosome maturation. Phagosome maturation arrest by Mtb involves multiple effectors and much remains unknown about this important aspect of Mtb pathogenesis. In this study, we found that interleukin 16 (IL-16) is elevated in the serum samples of Tuberculosis (TB) patients and can serve as a specific target for treatment TB. There was a significant difference in IL-16 levels among active TB, latent TB infection (LTBI), and non-TB patients. This study first revealed that macrophages are the major source of IL-16 production in response to Mtb infection, and elucidated that IL-16 can promote Mtb intracellular survival by inhibiting phagosome maturation and suppressing the expression of Rev-erbα which can inhibit IL-10 secretion. The experiments using zebrafish larvae infected with M. marinum and mice challenged with H37Rv demonstrated that reducing IL-16 levels resulted in less severe pathology and improved survival, respectively. In conclusion, this study provided direct evidence that Mtb hijacks the host macrophages-derived interleukin 16 to enhance intracellular growth. It is suggesting the immunosuppressive role of IL-16 during Mtb infection, supporting IL-16 as a promising therapeutic target.

AbstractObjective This study aimed to evaluate the combined efficacy of hyperthermia and chemotherapy using a bladder cancer organoid model and to explore hyperthermia-related molecular pathways.Method Tumor organoids were generated by embedding RT4 bladder cancer cells into Matrigel. The resulting organoids were treated with pirarubicin or gemcitabine at 37 °C or 42 °C. Proliferation was determined by Ki67 immunofluorescence staining, and apoptosis was assessed using a TdT-mediated dUTP nick end labeling (TUNEL) assay. RNA sequencing was used to identify the differentially expressed genes.Results Bladder cancer organoids were successfully established and exhibited robust proliferative abilities. Treatment with gemcitabine or pirarubicin under hyperthermic conditions caused pronounced structural damage to the organoids and increased cell death compared to that in the normothermically treated group. Furthermore, Ki67 labeling and TUNEL assays showed that the hyperthermia chemotherapy group showed a significantly reduced proliferation rate and high level of apoptosis. Finally, RNA sequencing revealed the IFN-γ signaling pathway to be associated with hyperthermia.Conclusion Overall, hyperthermia combined with chemotherapy exerted better therapeutic effects than those of normothermic chemotherapy in grade 1-2 non-muscle-invasive bladder cancer, potentially through activation of the IFN-γ-JAK-STAT pathway.

BackgroundChronic viral infections, such as Human Immunodeficiency Virus (HIV), and their reactivation are considered potential contributing factors to Long-Corona Virus Disease (LC). However, research on the long-term sequelae of Long-COVID in individuals with HIV is limited.MethodsWe conducted a case-control study involving a total of 84 participants categorized into two groups: people living with HIV (PLWH) and people not living with HIV (PNLWH) within the six-month post-infection LC population. Differences in sequelae symptoms, cardiovascular biomarkers (VCAM-1, ICAM-1, and ACE2), Severe Acute Respiratory Syndrome Coronavirus 2 neutralization antibodies (SARS-CoV-2 nAb) and cytokines (IFN-γ, IL-6, and IL-17) were analyzed between the two groups.ResultsAfter 6 months of infection, PLWH exhibited significantly higher serum levels of ACE2, VCAM-1, and ICAM-1 (P < 0.01, respectively) compared to PNLWH with COVID-19. Additionally, sequelae symptoms were more pronounced in PNLWH, and there were no differences in serum levels of IFN-γ, TNF-α, IL-6, and IL-17 between the two groups (P > 0.05, respectively).ConclusionPLWH had lower symptoms of LC and reduced frequency of symptoms, increased cardiovascular risk factors, and no differences in levels of inflammation or SARS-CoV-2 nAb levels when compared to PNLWH.

ObjectiveTo investigate the association between plasma total homocysteine (tHcy) levels and behavioral and psychological symptoms of dementia (BPSD) in dementia with Lewy bodies (DLB) patients.MethodsA total of 82 DLB patients and 134 age-matched healthy controls were included in this study. DLB patients were assessed using the Mini-Mental Status Examination (MMSE), the Clinical Dementia Rating Scale (CDR), and the Neuropsychiatric Inventory (NPI). Plasma tHcy, serum vitamin B12, and folate levels were measured in all study participants. We used Spearman’s rank correlation test to analyze the association between tHcy concentrations and NPI scores, MMSE, CDR, and the duration of dementia in DLB patients.ResultsClinically significant BPSD was present in 92.7% of DLB patients. The most frequent BPSD were hallucinations (30.4%), apathy (30.4%), and delusions (26.8%). Elevated plasma tHcy levels were significantly associated with total NPI scores in DLB patients, particularly in 10 NPI sub-domains, except for agitation/aggression and disinhibition. No statistically significant association was found between plasma tHcy levels and MMSE, CDR, or dementia duration.LimitationsLongitudinal studies with larger sample sizes are required to further explore the relationship between tHcy levels and BPSD in DLB patients as the disease progresses.ConclusionOur study highlighted the high incidence of BPSD and was the first to show that BPSD is associated with elevated plasma tHcy levels in DLB patients in China. These results support the hypothesis that controlling homocysteine levels could offer a new direction for managing BPSD.

PurposeThe aim of this study is to compare mean platelet volume/platelet count ratio (PVPR) and other indicators’ predictive abilities. Simultaneously, a new nomogram for predicting recurrence-free survival (RFS) after gastrointestinal stromal tumors (GISTs) R0 resection was developed.MethodsFrom January 2010 to July 2019, 295 patients with GIST who were operated on at Harbin Medical University Cancer Hospital were retrospectively reviewed. With a 4-year RFS as the end point, using the Kaplan–Meier methods and log rank test, and then conducting Cox regression analysis, we compared and identified meaningful indicators for predicting prognosis. Finally, a nomogram was developed and validated using calibration curves.ResultsThe receiver operating characteristic curve indicated that a cutoff point of 0.044 was the ideal threshold for PVPR, and patients were divided into a high-PVPR group (≤0.044) and a low-PVPR group (>0.044). Kaplan–Meier curves suggested that PVPR>0.044 had obvious associations with better RFS (p < 0.001). In accordance with multivariate analysis, PVPR (>0.044 vs. ≤0.044) (p = 0.005), National Institutes of Health (NIH) risk category (p < 0.001), and Ki-67 (p = 0.005) were the independent prognostic indicators of RFS. Tumor size, gastrointestinal bleeding, mitotic index, NIH risk category, CD34, and Ki-67 all exhibited an obvious correlation with PVPR (all p < 0.05). The nomogram’s probability of concordance was 0.823, indicating that the nomogram predictions were well calibrated.ConclusionIn GISTs, RFS can be independently predicted by PVPR. Patients with higher PVPR have better RFS. The nomogram including PVPR could be used to assist clinical treatment decision-making.

Precisely capturing and manipulating microparticles is the key to exploring microscopic mysteries. Optical tweezers play a crucial role in facilitating these tasks. However, existing optical tweezers are limited by their dependence on specific beam modes, which restrict their ability to flexibly switch and manipulate optical traps, thereby limiting their application in complex scientific challenges. Here, we propose a new method to achieve type switching and manipulation of optical traps using a single structured beam via optical coherence engineering. A conjugate-model random structured beam with a switch is designed. By altering the state of the switch, we can change the type of optical cage, enabling the capture of different particle types. Furthermore, the range, strength, and position of the optical trap can be controlled by adjusting the initial beam parameters. We hope that optical coherence engineering will extend the capabilities of existing structured optical tweezers, paving the way for advances in future optical tweezers applications.

Huntington’s disease (HD) is a progressive neurodegenerative disorder characterized by motor dysfunction and cognitive decline. While retinal abnormalities have been documented in some HD patients and animal models, the nature of these abnormalities—specifically whether they originate in the inner or outer retina—remains unclear, particularly regarding their progression with age. This study investigates the retinal structure and function in HD transgenic mice (R6/1) compared to C57BL/6 J control mice at 2, 4, and 6 months of age, encompassing both pre-symptomatic and symptomatic stages of HD. Pathological assessments of the striatum and evaluations of motor function confirmed significant HD-related alterations in R6/1 mice at 6 months. Visual function was subsequently analyzed, accompanied by immunofluorescent staining of retinal and optic nerve tissues over time. Our findings revealed that R6/1 mice exhibited pronounced HD symptoms at 6 months, characterized by neuronal loss in the striatum and impaired locomotor abilities. Functionally, visual acuity declined at 6 months, while retinal light responses began to deteriorate by 4 months. Structurally, R6/1 mice demonstrated a global reduction in cone opsin expression as early as 2 months, with a decrease in rhodopsin levels at 4 months, alongside a thinner retinal structure compared to controls. Notably, rod bipolar cell populations were decreased at 6 months, exhibiting shorter dendritic branches and reduced synaptic connections with photoreceptors in the outer retina. Additionally, ganglion cell numbers in the inner retina decreased at 6 months, accompanied by aberrant neural fibers in the optic nerve. Microglial activation was evident at 4 months, while astrocytic activation was observed at 6 months. Aggregates of mutant huntingtin (mHTT) were first detected in the ganglion cell layer and optic nerve at 2 months, subsequently disseminating throughout all retinal layers with advancing age. These results indicate that retinal pathology in R6/1 mice manifests earlier in the outer retina than in the inner retina, which does not align with the progression of mHTT aggregation. Consequently, the R6/1 mouse retina may serve as a more effective model for elucidating the mechanisms underlying HD and evaluating potential therapeutic strategies, rather than functioning as an early diagnostic tool for the disease.

ABSTRACT Children diagnosed with severe tonsillar hypertrophy display discernible craniofacial features distinct from those with adenoid hypertrophy, prompting illuminating considerations regarding microbiota regulation in this non-inflammatory condition. The present study aimed to characterize the salivary microbial profile in children with tonsillar hypertrophy and explore the potential functionality therein. A total of 112 children, with a mean age of 7.79 ± 2.41 years, were enrolled and divided into the tonsillar hypertrophy (TH) group (n = 46, 8.4 ± 2.5 years old), adenoid hypertrophy (AH) group (n = 21, 7.6 ± 2.8 years old), adenotonsillar hypertrophy (ATH) group (n = 23, 7.2 ± 2.1 years old), and control group (n = 22, 8.6 ± 2.1 years old). Unstimulated saliva samples were collected, and microbial profiles were analyzed by 16S rRNA sequencing of V3–V4 regions. Diversity and composition of salivary microbiome and the correlation with parameters of overnight polysomnography and complete blood count were investigated. As a result, children with tonsillar hypertrophy had significantly higher α-diversity indices (P＜0.05). β-diversity based on Bray–Curtis distance revealed that the salivary microbiome of the tonsillar hypertrophy group had a slight separation from the other three groups (P＜0.05). The linear discriminant analysis effect size (LEfSe) analysis indicated that Gemella was most closely related to tonsillar hypertrophy, and higher abundance of Gemella, Parvimonas, Dialister, and Lactobacillus may reflect an active state of immune regulation. Meanwhile, children with different degrees of tonsillar hypertrophy shared similar salivary microbiome diversity. This study demonstrated that the salivary microbiome in pediatric tonsillar hypertrophy patients had different signatures, highlighting that the site of upper airway obstruction primarily influences the salivary microbiome rather than hypertrophy severity.IMPORTANCETonsillar hypertrophy is the most frequent cause of upper airway obstruction and one of the primary risk factors for pediatric obstructive sleep apnea (OSA). Studies have discovered that children with isolated tonsillar hypertrophy exhibit different craniofacial morphology features compared with those with isolated adenoid hypertrophy or adenotonsillar hypertrophy. Furthermore, characteristic salivary microbiota from children with OSA compared with healthy children has been identified in our previous research. However, few studies provided insight into the relationship between the different sites of upper airway obstruction resulting from the enlargement of pharyngeal lymphoid tissue at different sites and the alterations in the microbiome. Here, to investigate the differences in the salivary microbiome of children with tonsillar hypertrophy and/or adenoid hypertrophy, we conducted a cross-sectional study and depicted the unique microbiome profile of pediatric tonsillar hypertrophy, which was mainly characterized by a significantly higher abundance of genera belonging to phyla Firmicutes and certain bacteria involving in the immune response in tonsillar hypertrophy, offering novel perspectives for future related research.

Background: Female vulvar lichen sclerosus (VLS) is a chronic inflammatory skin disease of the vulva and its etiology is unknown. The main clinical symptoms are itching, burning and dyspareunia, and there is a lack of effective treatment. Methods: Clinical and follow-up data of women with VLS who underwent 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) from January 2023 to December 2023 in the department of obstetrics and gynecology, Qilu Hospital of Shandong University, were retrospectively analyzed. According to the inclusion and exclusion criteria, 36 patients with VLS who received ineffective conventional treatment (intractable VLS) were enrolled. Objective signs and subjective symptoms of vulvar lesions were recorded before treatment and 6 months after the end of treatment according to corresponding scoring criteria. Quality of life was evaluated using the Dermatology Life Quality Index (DLQI). Results: All patients received six sessions of ALA-PDT treatment and follow-up visits. After ALA-PDT treatment, 24 of 36 (66.67 %) patients' itching symptoms completely disappeared, 10 of 36 (27.78 %) patients' itching symptoms were relieved from severe to mild, and only 2 of 36 (5.56 %) patients' symptoms were not significantly relieved. 16 of 36 (44.4 %) patients' itching symptoms completely disappeared, 9 of 36 (25 %) patients' itching symptoms were relieved from severe to mild, and only 2 of 36 (5.56 %) patients still had severe pain. Compared to 22 patients with dyspareunia before treatment, only 9 patients still had dyspareunia with varying degrees of dyspareunia relief after treatment. Clinical signs improved significantly in the patients after ALA-PDT treatment. The total scores of clinical signs were (5.31 ± 1.67 vs 3.67 ± 1.71) before and after treatment. All patients showed improvement in DLQI after treatment. The main side effects of ALA-PDT were pain, erythema and swelling which were transient and tolerable. All patients were “satisfied” or “very satisfied” with the results of the treatment. Conclusions: ALA-PDT is a safe and effective treatment for women with intractable vulva lichen sclerosus.

The high catalytic activity of photocatalysts is greatly influenced by the efficient separation of photogenerated charge carriers. In this study, six g‐C3N4‐based COFs are designed and synthesized, and CN‐203 is identified as the most efficient photocatalyst through experimental screening. Quantitative measurements reveal that singlet oxygen production is ≈100 times that of ·O2− and 5000 times that of ·OH. When combined with PMS, CN‐203 exhibits degradation rates for RhB and TC that are ≈30 (k = 0.0293 s−1) and 10 (k = 0.2940 min−1) times faster than those of CN550(RhB, k = 0.0531 min−1; TC, k = 0.0301 min−1), respectively. Structural simulations and calculations show that the modified CN‐203 have better electron–hole separation in the excited state, and the energy gap between HOMO and LUMO is significantly reduced after modification. The study also revealed the structure–function relationship between the modification of the same site with different functional groups and its effect on photocatalysis. Overall, this study provides valuable insights into the relationship between surface structure and photocatalytic applications.

The key odorants contributing to the warmed-over flavor (WOF) of reheated precooked stewed beef were characterized using a sensomics approach. Overall, 36 odorants were identified, and based on flavor dilution factors, odor activity values, aroma recombination, and omission test, 11 compounds mainly derived from lipid oxidation were characterized as the key odorants contributing to the formation of WOF. In particular, 3-(methylthio)propanal, which was positively correlated with meaty aroma, was implicated in an overall increase in WOF. Thus, these odorants were elected as potential markers of WOF in the reheated precooked stewed beef. In summary, the WOF of the precooked stewed beef could be attributed to an overall increase in lipid oxidation products and a decrease in the odorants with desirable aromas. The characterization of WOF in precooked stewed beef will aid in the flavor quality control of precooked stewed beef dishes.

Understanding the effects of microwave irradiation and thermal treatment on the dynamic compression and fragmentation properties of rocks is essential to quantify energy consumption in rock engineering. In this study, Fangshan granite (FG) specimens were exposed to microwave irradiation and heat treatment. The damage of FG specimens induced by these two methods was compared using X-ray CT scanning and ultrasonic wave method. The temperatures of FG after microwave irradiation and thermal treatment were effectively evaluated using a newly proposed technique. A novelty method for precisely determining the geometric features of fragments is developed to estimate the fragmentation energy. Thus, the dynamic uniaxial compressive strength (UCS), the dynamic fragmentation characteristics, and the fragmentation energy of FG after these two pretreatment methods can be reasonably compared. The noticeable distinction of loading rate effect on the dynamic UCS of FG between these two pretreatment methods is first observed. A relationship is established between the dynamic UCS and the damage induced by microwave irradiation and heat treatment. Moreover, fragmentation energy fan analysis is introduced to accurately compare the fragmentation properties of FG after two pretreatment methods in dynamic compression tests.

Abstract The DC multi‐port converter's applications are increasing owing to its favourable features, including variable control mode, high power density, and bi‐directional power supply. On the other hand, the impedance interaction between each port of the electrolytic capacitor‐less DC multi‐port converter may generate an instability. To address the above mentioned problem, a method is proposed in this paper for reshaping the impedances of the energy storage converter by constructing a virtual impedance connected in parallel with the output impedance of the electrolytic capacitor‐less DC multi‐port converter. Furthermore, this paper introduces the stability criterion based on the unified impedance theory, which classifies a converter as either the bus current‐controlled converter or the bus voltage‐controlled converter. The proposed control approaches raise the magnitude of the output impedance of the electrolytic capacitor‐less DC multi‐port converter to satisfy the unified impedance theory criterion without modifying each port. The simulation results show that the proposed method is better than the traditional methods, and comprehensive experimental results are provided to validate the proposed methods.

Abstract Understanding the fluorescence resonance energy transfer (FRET) of metal nanoparticles at the atomic level has long been a challenge due to the lack of accurate systems with definite distance and orientation of molecules. Here we present the realization of achieving FRET between two atomically precise copper nanoclusters through cocrystallization-induced spatial confinement. In this study, we demonstrate the establishment of FRET in a cocrystallized Cu8(p-MBT)8(PPh3)4@Cu10(p-MBT)10(PPh3)4 system by exploiting the overlapping spectra between the excitation of the Cu10(p-MBT)10(PPh3)4 cluster and the emission of the Cu8(p-MBT)8(PPh3)4 cluster, combined with accurate control over the confined space between the two nanoclusters. Density functional theory is employed to provide deeper insights into the role of the distance and dipole orientations of molecules to illustrate the FRET procedure between two cluster molecules at the electronic structure level.

Abstract Background TTN is a complex gene with large genomic size and highly repetitive structure. Pathogenic variants in TTN have been reported to cause a range of skeletal muscle and cardiac disorders. Homozygous or compound heterozygous mutations tend to cause a wide spectrum of phenotypes with congenital or childhood onset. The onset and severity of the features were considered to be correlated with the types and location of the TTN variants. Methods Whole-exome sequencing was performed on three unrelated families presenting with fetal akinesia deformation sequence (FADS), mainly characterized by reduced fetal movements and limb contractures. Sanger sequencing was performed to confirm the variants. RT-PCR analysis was performed. Results TTN c.38,876–2 A > C, a meta transcript-only variant, with a second pathogenic or likely pathogenic variant in trans, was observed in five affected fetuses from the three families. Sanger sequencing showed that all the fetal variants were inherited from the parents. RT-PCR analysis showed two kinds of abnormal splicing, including intron 199 extension and skipping of 8 bases. Conclusions Here we report on three unrelated families presenting with FADS caused by four TTN variants. In addition, our study demonstrates that pathogenic meta transcript-only TTN variant can lead to defects which is recognizable prenatally in a recessive manner.

Abstract Tissue specificity is a fundamental property of an organ that affects numerous biological processes, including aging and longevity, and is regulated by the circadian clock. However, the distinction between circadian-affected tissue specificity and other tissue specificities remains poorly understood. Here, using multi-omics data on circadian rhythms in mice, we discovered that approximately 35% of tissue-specific genes are directly affected by circadian regulation. These circadian-affected tissue-specific genes have higher expression levels and are associated with metabolism in hepatocytes. They also exhibit specific features in long-reads sequencing data. Notably, these genes are associated with aging and longevity at both the gene level and at the network module level. The expression of these genes oscillates in response to caloric restricted feeding regimens, which have been demonstrated to promote longevity. In addition, aging and longevity genes are disrupted in various circadian disorders. Our study indicates that the modulation of circadian-affected tissue specificity is essential for understanding the circadian mechanisms that regulate aging and longevity at the genomic level.

Abstract Background Collagen (COL) genes, play a key role in tumor invasion and metastasis, are involved in tumor extracellular matrix (ECM)-receptor interactions and focal adhesion pathways. However, studies focusing on the diagnostic value of the COL4 family in stomach adenocarcinoma (STAD) are currently lacking. Methods The TCGA database was employed to retrieve the clinical features and RNA sequencing expression profiles of patients with STAD. We conducted an investigation to examine the expression disparities between STAD and adjacent normal tissues. Kaplan-Meier survival analysis was utilized to assess their prognostic significance, while Spearman correlation analysis was employed to determine their association with immune checkpoint genes and immunomodulatory molecules. Furthermore, GO and KEGG analyses were performed on the COL4s-related genes, revealing potential biological pathways through gene set enrichment analysis (GSEA). Subsequently, we explored the extent of immune infiltration of the COL4 family in STAD using the TIMER database. Lastly, the expression levels of the COL4 family in STAD were further validated through quantitative PCR (qPCR) and western blot techniques. Results The expression levels of COL4A1/2 were significantly upregulated, while COL4A5/6 were conspicuously downregulated in STAD. The survival analysis revealed that the upregulated COL4s indicated poorer overall survival, first progression and post-progression survival outcomes. Additionally, our findings demonstrated a positive correlation between the expressions of COL4A1/2/3/4 and the infiltration of immune cells, including CD8 + T cells, dendritic cells, macrophages, neutrophils and CD4 + T cells. Further correlation analysis uncovered a favorable association between the expression of COL4A1/2/3/4 and various crucial immunomodulatory molecules, immunological checkpoint molecules, and chemokines. Quantitative PCR analysis confirmed that the expression patterns of COL4A1/3/4/6 genes aligned with the finding from the TCGA database. However, gastric cancer cells exhibited downregulation of COL4A2. Consistently, the protein level of COL4A1 was elevated, whereas the protein level of COL4A2 was reduced in the gastric cancer cell lines. Conclusion COL4s could potentially serve as biomarkers for diagnosing and predicting the prognosis of STAD.

Abstract College students represent a burgeoning force in mass entrepreneurship, underscoring the critical need to nurture their entrepreneurial endeavors. This study adopts a quantitative method, surveying 33,660 Chinese college students engaged in entrepreneurial activities. It examines the impact of various entrepreneurial policies and regional entrepreneurship spirit on these students’ decision-making processes. The findings reveal a positive correlation between entrepreneurial policies and entrepreneurial decision-making among college students, with regional entrepreneurship spirit serving as a mediator. Gender influences the relationship between regional entrepreneurship spirit and entrepreneurial decision-making, primarily moderating the effects of supply-based and environmentally-oriented policies. Entrepreneurship must be deeply integrated within China’s unique social networks and informal institutional frameworks. The moderating influence of gender also highlights differing policy impacts among various student groups. This research contributes to the enhancement and understanding of the policy support mechanism’s effect on college students and underscores the necessity for precise implementation of entrepreneurship policies tailored to college students.

Abstract Background Residual risk assessment for acute coronary syndrome (ACS) patients after sufficient medical management remains challenging. The usefulness of measuring high-sensitivity C-reactive protein (hsCRP) and remnant cholesterol (RC) in assessing the level of residual inflammation risk (RIR) and residual cholesterol risk (RCR) for risk stratification in these patients needs to be evaluated. Methods Patients admitted for ACS on statin treatment who underwent percutaneous coronary intervention (PCI) between March 2016 and March 2019 were enrolled in the analysis. The included patients were stratified based on the levels of hsCRP and RC during hospitalization. The primary outcome was ischemic events at 12 months, defined as a composite of cardiac death, myocardial infarction, or stroke. The secondary outcomes included 12-month all-cause death and cardiac death. Results Among the 5778 patients, the median hsCRP concentration was 2.60 mg/L and the median RC concentration was 24.98 mg/dL. The RIR was significantly associated with ischemic events (highest hsCRP tertile vs. lowest hsCRP tertile, adjusted hazard ratio [aHR]: 1.52, 95% confidence interval [CI]: 1.01–2.30, P = 0.046), cardiac death (aHR: 1.77, 95% CI:1.02–3.07, P = 0.0418) and all-cause death (aHR: 2.00, 95% CI: 1.24–3.24, P = 0.0048). The RCR was also significantly associated with these outcomes, with corresponding values for the highest tertile of RC were 1.81 (1.21–2.73, P = 0.0043), 2.76 (1.57–4.86, P = 0.0004), and 1.72 (1.09–2.73, P = 0.0208), respectively. The risks of ischemic events (aHR: 2.80, 95% CI: 1.75–4.49, P

Abstract Aims/Introduction Machine learning algorithms based on the artificial neural network (ANN), support vector machine, naive Bayesian or logistic regression model are commonly used to identify diabetes. This study investigated which approach performed the best and whether muscle strength provided any incremental benefit in identifying undiagnosed diabetes in Chinese adults. Methods This cross‐sectional study enrolled 4,482 eligible participants from eight provinces in China, who were randomly divided into the training dataset (n = 3,586) and the testing dataset (n = 896). Muscle strength was assessed by handgrip strength and the number of chair stands in the 30‐s chair stand test. An oral glucose tolerance test was used to ascertain undiagnosed diabetes. The areas under the curve (AUCs) were calculated accordingly and compared with each other. Results Of the included participants, 233 had newly diagnosed diabetes. All the four machine learning algorithms, which were developed based on nonlaboratory parameters, showed acceptable discriminative ability in identifying undiagnosed diabetes (all AUCs >0.70), with the ANN approach performing the best (AUC 0.806). Adding handgrip strength or the 30‐s chair stand test to this approach did not increase the AUC further (P = 0.39 and 0.26, respectively). Furthermore, compared with the New Chinese Diabetes Risk Score, the ANN approach showed a larger AUC in identifying undiagnosed diabetes (Pcomparison

Abstract Background Acute coronary syndrome due to coronary artery embolism in the setting of ascending aortic thrombus is an uncommon condition, even rarer when there is no aortic pathology such as aneurysm, severe atherosclerosis, aortic dissection, or thrombophilia (whether inherited or acquired). Case presentation We report a case of a 58-year-old male presented with acute chest pain, electrocardiogram showing non-ST-elevation acute coronary syndrome. The computed tomography angiography of coronary artery revealed a mural thrombus in the proximal part of ascending aorta, located above the left coronary artery ostium, without any aortic pathologies. With the exception of hypertension and cigarette smoking, no other risk factors were identified in this patient that may increase the risk of thrombosis. Given the life-threatening risk of interventional therapy and surgery, the patient determinedly opted for anticoagulant and dual antiplatelet therapy. Then he experienced the reoccurrence of chest pain after 6-day treatment, progressed to anterior and inferior ST-segment elevation myocardial infarction. Coronary artery embolism originating from the ascending aortic thrombus was suspected. Considering the hemodynamic instability of the patient, the medical treatment was continued and bridged to warfarin and aspirin after discharge. Follow-up computed tomography angiography at 6 months showed no obstruction in coronary artery and complete resolution of the thrombus. No thromboembolic events occurred henceforward. Conclusions Acute coronary syndrome could be a manifestation of secondary coronary embolism due to ascending aortic thrombus. Currently, there is no standardized guideline for the treatment of aortic mural thrombus, individualized treatment is recommended. When surgical therapy is not applicable for the patient, anticoagulation and dual antiplatelet treatment are alternative treatments that may successfully lead to the resolution of the aortic thrombus.

Abstract Background We describe a case in which bilateral optic nerve infiltration and leukemic retinopathy were the initial signs of disease relapse in a patient with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+-ALL) with central nervous system (CNS) involvement. Case presentation A 65-year-old Asian female with Ph+-ALL in complete remission presented at our institution with symptoms of visual disturbance, central scotoma and pain with eye movement in both eyes for a 1-month duration. Ophthalmic examination revealed remarkable optic disc swelling with multiple flame-shaped peripapillary hemorrhages, retinal venous dilation and retinal hemorrhages in both eyes. She was subsequently referred to the treating oncologist and diagnosed with Ph+-ALL relapse with multiple relapsed diseases involving the bone marrow and CNS. After intrathecal (IT) therapy, her visual acuity dramatically improved, and her leukemic infiltrates decreased. Conclusions To the best of our knowledge, this is the first case report of ALL relapse with CNS involvement presenting as bilateral optic nerve infiltration and leukemic retinopathy in an adult. Hence, we highlight the priority and sensitivity of ophthalmic examinations, as they are noninvasive methods for detecting leukemia relapse.

Abstract Histone deacetylase (HDAC) serves as a critical molecular regulator in the pathobiology of various malignancies and have garnered attention as a viable target for therapeutic intervention. A variety of HDAC inhibitors (HDACis) have been developed to target HDACs. Many preclinical studies have conclusively demonstrated the antitumor effects of HDACis, whether used as monotherapy or in combination treatments. On this basis, researchers have conducted various clinical studies to evaluate the potential of selective and pan-HDACis in clinical settings. In our work, we extensively summarized and organized current clinical trials, providing a comprehensive overview of the current clinical advancements in targeting HDAC therapy. Furthermore, we engaged in discussions about several clinical trials that did not yield positive outcomes, analyzing the factors that led to their lack of anticipated therapeutic effectiveness. Apart from the experimental design factors, issues such as toxicological side effects, tumor heterogeneity, and unexpected off-target effects also contributed to these less-than-expected results. These challenges have naturally become significant barriers to the application of HDACis. Despite these challenges, we believe that advancements in HDACi research and improvements in combination therapies will pave the way or lead to a broad and hopeful future in the treatment of solid tumors.

Abstract Down-polyethylene film material has been introduced for the first time as an excellent non-frame sound absorber, showing a distinctively outstanding performance. It contains down fiber adjacent to each other without firm connection in between, forming a structure of elastic fiber network. The unique structure has broadband response to sound wave, showing non-synchronous vibration in low and middle frequency and synchronous vibration in middle and high frequency. The broadband resonance in middle and high frequency allows the structure to achieve complete sound absorption in resonance frequency band. Moreover, down-polyethylene film material possesses forced vibration, corresponding sound absorption coefficient has been obtained based on vibration theory. The down-film sound absorption material has the characteristics of light weight, soft, environment-friendly, and has excellent broadband sound absorption performance.

Abstract This study elaborates on the design, fabrication, and data analysis details of SPEED, a recently proposed smartphone-based digital polymerase chain reaction (dPCR) device. The dPCR chips incorporate partition diameters ranging from 50 μm to 5 μm, and these partitions are organized into six distinct blocks to facilitate image processing. Due to the superior thermal conductivity of Si and its potential for mass production, the dPCR chips were fabricated on a Si substrate. A temperature control system based on a high-power density Peltier element and a preheating/cooling PCR protocol user interface shortening the thermal cycle time. The optical design employs four 470 nm light-emitting diodes as light sources, with filters and mirrors effectively managing the light emitted during PCR. An algorithm is utilized for image processing and illumination nonuniformity correction including conversion to a monochromatic format, partition identification, skew correction, and the generation of an image correction mask. We validated the device using a range of deoxyribonucleic acid targets, demonstrating its potential applicability across multiple fields. Therefore, we provide guidance and verification of the design and testing of the recently proposed SPEED device.

Abstract Background Previous evidence showed a possible link of dyslipidemia with bone health. Nevertheless, the correlation of remnant cholesterol (RC) with bone mineral density (BMD) has yet to be well investigated. This study investigated the association of RC with total spine BMD in general Americans. Methods This study explored the relationship of RC with total spine BMD in subjects aged ≥ 20 years from the National Health and Nutrition Examination Survey (NHANES) 2013–2018. After adjusting for covariates, multivariate linear regression and stratified analyses were conducted to determine the correlation of serum RC with total spine BMD in adult Americans. Restricted cubic spline (RCS) was applied to examine the nonlinear association of serum RC with total spine BMD. Results This study included 3815 individuals ≥ 20 years old, 1905 (49.93%) of whom were men and 1910 (50.07%) of whom were women. After adjusting for all covariates, the results showed a negative relationship of serum RC with total spine BMD (β= -0.024, 95% CI: -0.039, -0.010). The interaction tests of age, sex, race, and BMI showed no statistically significant effects on the association. The RCS also indicated a negative linear correlation of serum RC with total spine BMD (nonlinear P = 0.068, overall P

Abstract Background Previous studies have shown that the relationship between high-density lipoprotein cholesterol (HDL-C) and stroke is controversial, and the association between the platelet/high-density lipoprotein cholesterol ratio (PHR), a novel marker for inflammation and hypercoagulability states, and stroke has not been established. Methods This study presents an analysis of cross-sectional data from the 2005–2018 National Health and Nutrition Examination Survey (NHANES). Stroke history, HDL-C levels, and platelet counts were obtained during cross-sectional surveys. The PHR was calculated as the ratio of the number of platelets to HDL-C concentration. Weighted logistic regression was used to assess the associations of HDL-C and the PHR with stroke. Nonlinearity of this relationship was determined through restricted cubic splines (RCSs) and two-piecewise linear regression for identifying inflection points. Furthermore, Cox regression was utilized to prospectively analyze the associations of the PHR and HDL-C concentration with cardiovascular disease (CVD) mortality in stroke survivors. Results A total of 27,301 eligible participants were included in the study; mean age, 47.28 years and 50.57% were female, among whom 1,040 had a history of stroke. After full adjustment, the odds ratio (OR) of stroke associated with a per standard deviation (SD) increase in the PHR was estimated at 1.13 (95% confidence interval (CI): 1.03 − 1.24, P = 0.01), and the OR of stroke associated with a per SD increase in HDL-C was 0.95 (95% CI: 0.86–1.05, P = 0.30). The RCS indicated a nonlinear relationship for both variables (P PHR = 0.018 and P HDL-C = 0.003), and further piecewise linear regression identified inflection points at PHR = 223.684 and HDL-C = 1.4 mmol/L. Segmental regression indicated that in the PHR ≥ 223.684 segment, the estimated OR of stroke associated with a per-SD increase in the PHR was 1.20 (95% CI: 1.09 − 1.31, P 0.05). Furthermore, Cox regression and RCS showed that a per-SD increase in the PHR was linearly associated with a greater risk of CVD mortality among stroke survivors (HR: 1.14, 95% CI: 1.06 − 1.22, P

Abstract Background Immunosuppression is a leading cause of septic death. Therefore, it is necessary to search for biomarkers that can evaluate the immune status of patients with sepsis. We assessed the diagnostic and prognostic value of low-density neutrophils (LDNs) and myeloid-derived suppressor cells (MDSCs) subsets in the peripheral blood mononuclear cells (PBMCs) of patients with sepsis. Methods LDNs and MDSC subsets were compared among 52 inpatients with sepsis, 33 inpatients with infection, and 32 healthy controls to investigate their potential as immune indicators of sepsis. The percentages of LDNs, monocytic MDSCs (M-MDSCs), and polymorphonuclear MDSCs (PMN-MDSCs) in PBMCs were analyzed. Sequential organ failure assessment (SOFA) scores, C-reactive protein (CRP), and procalcitonin (PCT) levels were measured concurrently. Results The percentages of LDNs and MDSC subsets were significantly increased in infection and sepsis as compared to control. MDSCs performed similarly to CRP and PCT in diagnosing infection or sepsis. LDNs and MDSC subsets positively correlated with PCT and CRP levels and showed an upward trend with the number of dysfunctional organs and SOFA score. Non-survivors had elevated M-MDSCs compared with that of patients who survived sepsis within 28 days after enrollment. Conclusions MDSCs show potential as a diagnostic biomarker comparable to CRP and PCT, in infection and sepsis, even in distinguishing sepsis from infection. M-MDSCs show potential as a prognostic biomarker of sepsis and may be useful to predict 28-day hospital mortality in patients with sepsis.

Abstract Background Glycyrrhiza inflata Bat. and Glycyrrhiza uralensis Fisch. are both original plants of ‘Gan Cao’ in the Chinese Pharmacopoeia, and G. uralensis is currently the mainstream variety of licorice and has a long history of use in traditional Chinese medicine. Both of these species have shown some degree of tolerance to salinity, G. inflata exhibits higher salt tolerance than G. uralensis and can grow on saline meadow soils and crusty saline soils. However, the regulatory mechanism responsible for the differences in salt tolerance between different licorice species is unclear. Due to land area-related limitations, the excavation and cultivation of licorice varieties in saline-alkaline areas that both exhibit tolerance to salt and contain highly efficient active substances are needed. The systematic identification of the key genes and pathways associated with the differences in salt tolerance between these two licorice species will be beneficial for cultivating high-quality salt-tolerant licorice G. uralensis plant varieties and for the long-term development of the licorice industry. In this research, the differences in growth response indicators, ion accumulation, and transcription expression between the two licorice species were analyzed. Results This research included a comprehensive comparison of growth response indicators, including biomass, malondialdehyde (MDA) levels, and total flavonoids content, between two distinct licorice species and an analysis of their ion content and transcriptome expression. In contrast to the result found for G. uralensis, the salt treatment of G. inflata ensured the stable accumulation of biomass and total flavonoids at 0.5 d, 15 d, and 30 d and the restriction of Na+ to the roots while allowing for more K+ and Ca2+ accumulation. Notably, despite the increase in the Na+ concentration in the roots, the MDA concentration remained low. Transcriptome analysis revealed that the regulatory effects of growth and ion transport on the two licorice species were strongly correlated with the following pathways and relevant DEGs: the TCA cycle, the pentose phosphate pathway, and the photosynthetic carbon fixation pathway involved in carbon metabolism; Casparian strip formation (lignin oxidation and translocation, suberin formation) in response to Na+; K+ and Ca2+ translocation, organic solute synthesis (arginine, polyamines, GABA) in response to osmotic stresses; and the biosynthesis of the nonenzymatic antioxidants carotenoids and flavonoids in response to antioxidant stress. Furthermore, the differential expression of the DEGs related to ABA signaling in hormone transduction and the regulation of transcription factors such as the HSF and GRAS families may be associated with the remarkable salt tolerance of G. inflata. Conclusion Compared with G. uralensis, G. inflata exhibits greater salt tolerance, which is primarily attributable to factors related to carbon metabolism, endodermal barrier formation and development, K+ and Ca2+ transport, biosynthesis of carotenoids and flavonoids, and regulation of signal transduction pathways and salt-responsive transcription factors. The formation of the Casparian strip, especially the transport and oxidation of lignin precursors, is likely the primary reason for the markedly higher amount of Na+ in the roots of G. inflata than in those of G. uralensis. The tendency of G. inflata to maintain low MDA levels in its roots under such conditions is closely related to the biosynthesis of flavonoids and carotenoids and the maintenance of the osmotic balance in roots by the absorption of more K+ and Ca2+ to meet growth needs. These findings may provide new insights for developing and cultivating G. uralensis plant species selected for cultivation in saline environments or soils managed through agronomic practices that involve the use of water with a high salt content.

Infertility is a disease of impaired fertility. With socioeconomic development, changes in human lifestyles, and increased environmental pollution, the problem of low human fertility has become increasingly prominent. The incidence of global infertility is increasing every year. Many factors lead to infertility, and common female factors include tubal factors, ovulation disorders, endometriosis, and immune factors. The gut microbiota is involved in many physiological processes, such as nutrient absorption, intestinal mucosal growth, glycolipid metabolism, and immune system regulation. An altered gut flora is associated with female infertility disorders such as polycystic ovary syndrome (PCOS), endometriosis (EMs), and premature ovarian failure (POF). Dysbiosis of the gut microbiota directly or indirectly contributes to the development of female infertility disorders, which also affect the homeostasis of the gut microbiota. Identifying the etiology and pathogenesis of infertility in patients is the focus of reproductive medicine physicians. We studied the developmental mechanism between the gut microbiota and PCOS, EMs, and POF from a new perspective, providing new ideas for diagnosing and treating female infertility diseases and specific reference values for eugenics.

Abstract Obstructive sleep apnea syndrome (OSAS), characterized by chronic intermittent hypoxia (CIH), is an independent risk factor for aggravating non‐alcoholic steatohepatitis (NASH). The prevailing mouse model employed in CIH research is inadequate for the comprehensive exploration of the impact of CIH on NASH development due to reduced food intake observed in CIH‐exposed mice, which deviates from human responses. To address this issue, a pair‐feeding investigation with CIH‐exposed and normoxia‐exposed mice is conducted. It is revealed that CIH exposure aggravates DNA damage, leading to hepatic fibrosis and inflammation. The analysis of genome‐wide association study (GWAS) data also discloses the association between Eepd1, a DNA repair enzyme, and OSAS. Furthermore, it is revealed that CIH triggered selective autophagy, leading to the autophagic degradation of Eepd1, thereby exacerbating DNA damage in hepatocytes. Notably, Eepd1 liver‐specific knockout mice exhibit aggravated hepatic DNA damage and further progression of NASH. To identify a therapeutic approach for CIH‐induced NASH, a drug screening is conducted and it is found that Retigabine dihydrochloride suppresses CIH‐mediated Eepd1 degradation, leading to alleviated DNA damage in hepatocytes. These findings imply that targeting CIH‐mediated Eepd1 degradation can be an adjunctive approach in the treatment of NASH exacerbated by OSAS.

In the realm of renewable energy, the integration of wind power and hydrogen energy systems represents a promising avenue towards environmental sustainability. However, the development of cost-effective hydrogen energy storage solutions is crucial to fully realize the potential of hydrogen as a renewable energy source. By combining wind power generation with hydrogen storage, a comprehensive hydrogen energy system can be established. This study aims to devise a physiologically inspired optimization approach for designing a standalone wind power producer that incorporates a hydrogen energy system on a global scale. The optimization process considers both total cost and capacity loss to determine the optimal configuration for the system. The optimal setup for an off-grid solution involves the utilization of eight distinct types of compact horizontal-axis wind turbines. Additionally, a sensitivity analysis is conducted by varying component capital costs to assess their impact on overall cost and load loss. Simulation results indicate that at a 15 % loss, the cost of energy (COE) is $1.3772, while at 0 % loss, it stands at $1.6908. Capital expenses associated with wind turbines and hydrogen storage systems significantly contribute to the overall cost. Consequently, the wind turbine-hydrogen storage system emerges as the most cost-effective and reliable option due to its low cost of energy.

BackgroundMany studies worldwide have reported the association between mental health and blood pressure, but the results are mixed, and even contradictory. We aim to investigate the relationship between systolic and diastolic blood pressure and depression in the entire US population.MethodsThis study analyzed cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. All adults completed 3-4 blood pressure measurements after sitting quietly for 5 minutes. Depression was diagnosed based on the Patient Health Questionnaire (PHQ-9), with a score ≥10 defined as depression. Weighted logistic regression and restricted cubic splines (RCS) were used to assess the relationship between blood pressure and depression. Two-piecewise linear regression was used to determine the inflection point. Additionally, subgroup analyses and interaction tests were conducted to identify potential subgroups. Finally, two sensitivity analyses were conducted.ResultsA total of 26,581 American adults were included, with a mean age of 47.2 years, of whom 13,354 (49.54%) were male; 2,261 individuals were defined as depressed, with a weighted prevalence of 7.41%. All participants’ mean systolic blood pressure (SBP) was 121.7 mmHg, and the mean diastolic blood pressure (DBP) was 70.9 mmHg. RCS showed a nonlinear association between SBP and depression, while DBP showed a positive linear association with depression. Two-piecewise linear regression showed that the inflection point of the association between SBP and depression was 129.7 mmHg. Weighted logistic regression showed that after fully adjusting for depression-related risk factors, there was a significant positive correlation between per 10 mmHg increase in DBP and depression (OR: 1.06, 95% CI: 1.00-1.12, P=0.04); however, only on the left side of the inflection point, SBP tended to decrease the odds of depression (P =0.09). Furthermore, interaction analysis showed that the association between DBP and depression was significantly stronger in cancer patients (P for interaction=0.02); on the left side of the inflection point (

Background Although CA19-9 is an essential blood biomarker of pancreatic cancer (PC), its sensitivity and specificity are limited for early detection. Methods We analyzed the serum proprotein convertase subtilisin/kexin type 9 (sPCSK9) in PC patients, benign disease groups (BDG), and healthy controls (HC) by ELISA. Results Consistently, sPCSK9 was considerably lower in PC patients than in HC (Z = −2.546, P < 0.05), and sPCSK9 in PC patients was statistically significantly higher than in BDG (Z = −5.457, P < 0.001). sPCSK9 was linked to the invasion of lymph nodes (χ2 = 6.846, P < 0.01). According to ROC curves, combining sPCSK9 with CA19-9 could potentially enhance the diagnostic capability of CA19-9 in early-stage PC patients. Furthermore, the low sPCSK9 group (n = 41) exhibited statistically significantly prolonged overall survival compared to the high sPCSK9 group (n = 15), with median survival times of 27 months (95% CI [17.59–36.41]) and 11 months (95% CI [7.21–14.79]), respectively (P = 0.022). Conclusion The diagnostic performance of CA19-9 for early-stage PC patients could be improved by combining sPCSK9 with CA19-9. Moreover, the higher sPCSK9 group has a significantly shorter overall survival rate.

The global prevalence of obesity is rising year by year, which has become a public health problem worldwide. Many animal and clinical studies have shown that Lactiplantibacillus plantarum is considered an ideal probiotic and potential supplement for the treatment of obesity. In this study, we aimed to complete the genome sequence of L. plantarum HOM2217, which was isolated from human milk, and study its physiological characteristics and anti-obesity effects in 3T3-L1 cells and rats fed a high-fat diet (HFD) to determine its potential as a starter for functional food products. Whole-genome analysis demonstrated that HOM2217 contained a single circular chromosome of 3,267,529 bp with a GC content of 44.5% and one plasmid (62,350 bp) with a GC content of 38.5%. Compared to the reference strains, HOM2217 demonstrated superior tolerance to gastrointestinal conditions, higher adhesion to intestinal epithelial cell lines, potent antimicrobial activity against Enterobacter cloacae ATCC 13047, and effective cholesterol removal ability in vitro. Treatment with heat-killed HOM2217 significantly reduced lipid accumulation and intracellular triglyceride production in 3T3-L1 adipocytes. Daily treatment of HFD-fed rats with HOM2217 for 7 weeks decreased body weight, body weight gain, and body fat without changes in food intake. HOM2217 also significantly increased the serum high-density lipoprotein cholesterol (HDL-C) level, decreased the serum tumor necrosis factor (TNF-α) and increased short-chain fatty acid (SCFA) (formic acid, acetic acid, and butyric acid) levels in the cecum. Thus, HOM2217 could potentially prevent obesity in rats by inhibiting inflammatory responses and regulating lipid metabolism and SCFAs expression. Therefore, HOM2217 has potential as an alternative treatment for obesity.

IntroductionThere is growing evidence indicating a complex interaction between blood metabolites and atopic dermatitis (AD). The objective of this study was to investigate and quantify the potential influence of plasma metabolites on AD through Mendelian randomization (MR) analysis.MethodsOur procedures followed these steps: instrument variable selection, primary analysis, replication analysis, Meta-analysis of results, reverse MR analysis, and multivariate MR (MVMR) analysis. In our study, the exposure factors were derived from the Canadian Longitudinal Study on Aging (CLSA), encompassing 8,299 individuals of European descent and identifying 1,091 plasma metabolites and 309 metabolite ratios. In primary analysis, AD data, was sourced from the GWAS catalog (Accession ID: GCST90244787), comprising 60,653 cases and 804,329 controls. For replication, AD data from the Finnish R10 database included 15,208 cases and 367,046 controls. We primarily utilized the inverse variance weighting method to assess the causal relationship between blood metabolites and AD.ResultsOur study identified significant causal relationships between nine genetically predicted blood metabolites and AD. Specifically, 1-palmitoyl-2-stearoyl-GPC (16:0/18:0) (OR = 0.92, 95% CI 0.89–0.94), 1-methylnicotinamide (OR = 0.93, 95% CI 0.89–0.98), linoleoyl-arachidonoyl-glycerol (18:2/20:4) [1] (OR = 0.94, 95% CI 0.92–0.96), and 1-arachidonoyl-GPC (20:4n6) (OR = 0.94, 95% CI 0.92–0.96) were associated with a reduced risk of AD. Conversely, phosphate / linoleoyl-arachidonoyl-glycerol (18:2/20:4) [2] (OR = 1.07, 95% CI 1.04–1.10), docosatrienoate (22:3n3) (OR = 1.07, 95% CI 1.04–1.10), retinol (Vitamin A) / linoleoyl-arachidonoyl-glycerol (18:2/20:4) [2] (OR = 1.08, 95% CI 1.05–1.11), retinol (Vitamin A) / linoleoyl-arachidonoylglycerol (18:2/20:4) [1] (OR = 1.08, 95% CI 1.05–1.12), and phosphate / linoleoyl-arachidonoyl-glycerol (18:2/20:4) [1] (OR = 1.09, 95% CI 1.07–1.12 were associated with an increased risk of AD. No evidence of reverse causality was found in the previously significant results. MVMR analysis further confirmed that 1-palmitoyl-2-stearoyl-GPC (16:0/18:0) and 1-methylnicotinamide are independent and dominant contributors to the development of AD.ConclusionOur study revealed a causal relationship between genetically predicted blood metabolites and AD. This discovery offers specific targets for drug development in the treatment of AD patients and provides valuable insights for investigating the underlying mechanisms of AD in future research.

BackgroundHepatorenal syndrome (HRS) bears a very poor prognosis with unmet need for safe and effective therapies. This systematic review and meta-analysis aimed to re-assess safety and efficacy of terlipressin versus placebo or noradrenaline for HRS, based on previous randomized controlled trials (RCTs).MethodsPubMed, EMBASE, MEDLINE (OvidSP) and Cochrane registers were searched for trials reporting HRS treatment by terlipressin or noradrenaline. Search terms included: “hepatorenal syndrome”, “terlipressin”, “noradrenaline”, and corresponding synonyms. Comparisons between terlipressin, noradreanaline, placebo and albumin were included. Meta-analysis was conducted for treatment response (both HRS reversal and complete response), mortality and adverse events.Results15 RCTs were included, enrolling 1236 HRS patients (type 1: 1166, type 2: 70). Treatment with terlipressin+albumin resulted in significantly higher treatment response than placebo+albumin or albumin alone (risk ratio [RR]:2.75, 95% confidence interval [CI]:1.96 to 3.84; I2 = 28%, p = 0.23; n = 6). Noradrenaline was equally effective in treatment response compared to terlipressin (RR:1.19, 95% CI:0.96 to 1.46; I2 = 16%, p = 0.31; n = 7), but trials were limited by its non-blind design and small size. Sensitivity analysis showed no survival benefit with terlipressin compared to either placebo (RR:1.03, 95% CI:0.83 to 1.28; I2 = 0%, p = 0.72; n = 3) or noradreanline (RR:0.83, 95% CI:0.69 to 1.00; I2 = 4%, p = 0.39; n = 7) at 30 days of follow-up. Terlipressin carried higher risk of treatment-related adverse events compared to either placebo (RR:2.92, 95% CI:1.48 to 5.77; I2 = 0%, p = 0.75; n = 3) or noradrenaline (RR:2.45, 95% CI:1.37 to 4.37; I2 = 0%, p = 0.92; n = 5).ConclusionTerlipressin is superior to placebo, and comparable to noradreanline in treatment response, but survival benefit is lacking. Noradrenaline, with low certainty, may be a better alternative for HRS.

In response to China's national policy of “achieving carbon peak by 2030 and carbon neutrality by 2060″, and to promote the heating system of rural buildings in China's severe cold zone. Two heating schemes of the GSHP (Ground Source Heat Pump) system and the SGSHP (Solar Ground Source Heat Pump) system are designed and simulated for a single rural residential building in Harbin city. The results present that the outlet temperature of buried pipe in SGSHP system is 13.86 % higher than that in GSHP system, and coefficient of performance (COP) correspondingly increases 9.2 %. There is a better comprehensive performance for the SGSHP system in cold climates. The standard coal consumption of SGSHP system is about 72.35 % less than that of biomass boiler system, showing a greater energy efficiency. Compared to the local conventional biomass boiler system, the dynamic cost payback period of the SGSHP system amounts to 11 years, while yielding a net present value (NPV) of 10,800 CNY throughout the project's life cycle. The emissions of CO2, SO2, and dust are reduced by 2617.13 kg, 19.38 kg, and 14.535 kg respectively. The results indicate a great overall performance of the SGSHP system for residential heating in the cold climate zone. This research offers an energy efficient and eco-friendly alternative for the space heating of Chinese rural buildings in cold climates.

In the current study, the CN-CD30V10A battery tester, K-type temperature sensor, and RS485 are utilized to perform charging and discharging tests on the Panasonic 21,700 lithium-ion battery at various rates. The voltage and temperature changes are measured in real-time, with the data transmitted to the computer via RS485. Then a micro-thermal resistance method is proposed to calculate the equivalent thermal resistance of the cell core along the axial positive and negative poles, as well as along the radial outer circumference surface under anisotropic conditions. Based on the experimental results and the equivalent thermal resistance, an electrothermal coupling model is established for battery internal temperature estimation, taking into account anisotropy and temperature effects on heat transfer. Through the integration of the model and externally measured temperature, the internal temperature is accurately estimated. Moreover, the proposed model (Root-Mean-Square Error, RMSE=0.329) exhibits a significant improvement in accuracy compared to equivalent circuit model (RMSE=1.08), extended Kalman filter (RMSE=0.95), network extended Kalman filter (RMSE=0.58), and neural network unscented Kalman filter (RMSE=0.61). Specifically, the model achieves an approximately 76 % to 228 % reduction in RMSE compared to these methods.

Objectives The Action To promote brain HEalth iN Adults study aimed to determine the feasibility and applicability of recruitment using home blood pressure (BP) monitoring, routine blood biochemistry and videoconference measures of cognition, in adults at high risk of dementia.Design A decentralised double-blind, placebo-controlled, randomised feasibility trial with a four-stage screening process.Setting Conducted with participants online in the state of New South Wales, Australia.Participants Participants were aged 50–70 years with moderately elevated BP (systolic >120 and 80 and

Hypertensive disorders of pregnancy (HDP) are severe complications of pregnancy with high morbidity and are a major cause of increased maternal and infant morbidity and mortality. Currently, there is a lack of effective early diagnostic indicators and safe and effective preventive strategies for HDP in clinical practice, except for monitoring maternal blood pressure levels, the degree of proteinuria, organ involvement and fetal conditions. The intestinal microbiota consists of the gut flora and intestinal environment, which is the largest microecosystem of the human body and participates in material and energy metabolism, gene expression regulation, immunity regulation, and other functions. During pregnancy, due to changes in hormone levels and altered immune function, the intestinal microecological balance is affected, triggering HDP. A dysregulated intestinal microenvironment influences the composition and distribution of the gut flora and changes the intestinal barrier, driving beneficial or harmful bacterial metabolites and inflammatory responses to participate in the development of HDP and promote its malignant development. When the gut flora is dysbiotic and affects blood pressure, supplementation with probiotics and dietary fiber can be used to intervene. In this review, the interaction between the intestinal microbiota and HDP was investigated to explore the feasibility of the gut flora as a novel biomarker of HDP and to provide a new strategy and basis for the prevention and treatment of clinical HDP.

Background: Breast cancer stands as a globally significant contributor to both incidence rates and mortality among women. Approximately 10–15 % of women will face a diagnosis of an advanced yet potentially treatable stage of the disease. When individuals diagnosed with locally advanced breast cancer (LABC) exhibit resistance to preoperative chemotherapy and experience tumor progression, they unfortunately forfeit the opportunity for surgical intervention, thereby diminishing the prospects for a radical cure. Method: We conducted a prospective, single-arm cohort study aimed at evaluating the feasibility of locally modified radical resection for LABC with skin invasion. The primary endpoints encompassed overall survival (OS) and disease-free survival (DFS), whereas the secondary endpoint focused on the quality of life (QoL) among breast cancer patients. Results: Between March 2018 and December 2022, a total of 38 eligible patients were enrolled in this study. The Kaplan-Meier estimates for 1-year, 3-year, and 5-year DFS among all patients were 69.8 %, 53.3 %, and 37.5 %, respectively. Correspondingly, the OS rates were 100.0 %, 85.6 %, and 68.0 %. Both univariate and multivariate analyses revealed that patients with a history of neoadjuvant chemotherapy who exhibited stable or progressive disease had inferior DFS outcomes. Notably, patients demonstrated clinically meaningful and statistically significant enhancements in functional status and overall QoL. However, no notable improvement was observed in specific symptom domains. Conclusion: Patients with locally advanced breast cancer, specifically those presenting with T4 tumors, who undergo surgical intervention followed by postoperative adjuvant therapy, can attain favorable prognostic outcomes and experience an enhanced quality of life.

Abstract BackgroundRecently, the growing demand for pediatric sedation services outside the operating room has imposed a heavy burden on pediatric centers in China. There is an urgent need to develop a novel system for improved sedation services. ObjectiveThis study aimed to develop and implement a computerized system, the Pediatric Sedation Assessment and Management System (PSAMS), to streamline pediatric sedation services at a major children’s hospital in Southwest China. MethodsPSAMS was designed to reflect the actual workflow of pediatric sedation. It consists of 3 main components: server-hosted software; client applications on tablets and computers; and specialized devices like gun-type scanners, desktop label printers, and pulse oximeters. With the participation of a multidisciplinary team, PSAMS was developed and refined during its application in the sedation process. This study analyzed data from the first 2 years after the system’s deployment. Implementation (Results)From January 2020 to December 2021, a total of 127,325 sedations were performed on 85,281 patients using the PSAMS database. Besides basic variables imported from Hospital Information Systems (HIS), the PSAMS database currently contains 33 additional variables that capture comprehensive information from presedation assessment to postprocedural recovery. The recorded data from PSAMS indicates a one-time sedation success rate of 97.1% (50,752/52,282) in 2020 and 97.5% (73,184/75,043) in 2021. The observed adverse events rate was 3.5% (95% CI 3.4%‐3.7%) in 2020 and 2.8% (95% CI 2.7%-2.9%) in 2021. ConclusionsPSAMS streamlined the entire sedation workflow, reduced the burden of data collection, and laid a foundation for future cooperation of multiple pediatric health care centers.

BackgroundThe prevalence of venous thromboembolism (VTE) is high in patients with cancer and can often present as the first symptom of malignancy. Cancer-associated VTE is one of the most important risk factors contributing to cancer mortality, making its prevention and treatment critical for patients with lung cancer.MethodsWe systematically searched for observational studies that estimated the prevalence of VTE in patients with lung cancer. A comprehensive search of electronic databases, including PubMed, EMBASE and Cochrane Library, was systematically conducted from database inception through January 21, 2022. The qualities of included studies were assessed in three domains, including patient selection, comparison, and results. Random effects meta-analyses of the prevalence of VTE in lung cancer were conducted using the metaprop procedure. Chi-square test and I2 value were used to evaluate study heterogeneity.ResultsThirty-five studies involving 742,156 patients were considered eligible for this study. The pooled prevalence of VTE among patients with lung cancer was 5% (95% CI: 0.043–0.056, P = 0.000). The regional prevalence of VTE was 7% (95% CI: 0.06–0.08; I2 = 99.2%) in North America, 8% (95% CI: 0.06–0.10; I2 = 97.6%) in Asia, 6% (95% CI: 0.04–0.09; I2 = 95.9%) in Europe and 11% (95% CI: 0.07–0.15) in Australasia.ConclusionsThe prevalence of lung cancer-related VTE is high and region-specific. These results of this review emphasize the importance of understanding the incidence of lung cancer-related VTE and provide argue for VTE screening of patients with lung cancer.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier PROSPERO (CRD42022306400).

The nucleus accumbens (NAc), a central component of the brain’s reward circuitry, has been implicated in a wide range of behaviors and emotional states. Emerging evidence, primarily drawing from recent rodent studies, suggests that the function of the NAc in reward and aversion processing is multifaceted. Prolonged stress or drug use induces maladaptive neuronal function in the NAc circuitry, which results in pathological conditions. This review aims to provide comprehensive and up-to-date insights on the role of the NAc in motivated behavior regulation and highlights areas that demand further in-depth analysis. It synthesizes the latest findings on how distinct NAc neuronal populations and pathways contribute to the processing of opposite valences. The review examines how a range of neuromodulators, especially monoamines, influence the NAc’s control over various motivational states. Furthermore, it delves into the complex underlying mechanisms of psychiatric disorders such as addiction and depression and evaluates prospective interventions to restore NAc functionality.

Polycystic ovarian syndrome (PCOS) is a common heterogeneous reproductive endocrine metabolic disorder in women of reproductive age characterized by clinical and biochemical hyperandrogenemia, ovulation disorders, and polycystic ovarian morphology. Ferroptosis is a novel type of cell death driven by iron accumulation and lipid peroxidation. Ferroptosis plays a role in maintaining redox balance, iron metabolism, lipid metabolism, amino acid metabolism, mitochondrial activity, and many other signaling pathways linked to diseases. Iron overload is closely related to insulin resistance, decreased glucose tolerance, and the occurrence of diabetes mellitus. There is limited research on the role of ferroptosis in PCOS. Patients with PCOS have elevated levels of ferritin and increased reactive oxygen species in ovarian GCs. Studying ferroptosis in PCOS patients is highly important for achieving personalized treatment. This article reviews the progress of research on ferroptosis in PCOS, introduces the potential connections between iron metabolism abnormalities and oxidative stress-mediated PCOS, and provides a theoretical basis for diagnosing and treating PCOS.

Introduction: The development of small molecule modulators rooted the plant resistance mechanism represents a compelling strategy for improving plant resistance and fortifying food security. Systemins induced by wounds can activate a wide range of plant resistance responses, but compounds that regulate the systemin signaling pathway have yet to be found. Objectives: This study aimed to provide a strategy for the development of small molecule modulators based on virtual screening of systemin receptors. Methods: A systemin receptor model was established for virtual screening, leading to the identification of chemical structure with high binding affinity through molecular docking. Subsequently, the synthesized compound underwent evaluation for its potential to enhance plant resistance against viruses through frictional inoculation. The underlying mechanism of the target compound was analyzed using proteomics. Results: Through virtual screening, a promising active compound, F1, was identified and further optimized. Molecular docking showed that they had the ability to bind SR160. Some of the targeted compounds exhibited potential in enhancing plant resistance against Tobacco mosaic virus (TMV) and Cucumber mosaic virus (CMV). Notably, compound F26 showed satisfactory activity against TMV with an EC50 value of 70.6 μg/mL. The analysis of plant response following treatment with F26 indicated that it may reinforce the plant’s defense mechanisms against viruses by augmenting the wound signaling pathway.

In modern war or daily life, blast-induced traumatic brain injury (bTBI) is a growing health concern. Our previous studies demonstrated that inflammation was one of the main features of bTBI, and CD28-activated T cells play a central role in inflammation. However, the mechanism of CD28 in bTBI remains to be elucidated. In this study, traumatic brain injury model induced by chest blast exposure in male mice was established, and the mechanism of CD28 in bTBI was studied by elisa, immunofluorescence staining, flow cytometry analysis and western blot. After exposure to chest shock wave, the inflammatory factors IL-4, IL-6 and HMGB1 in serum were increased, and CD3+ T cells, CD4+ and CD8+ T cell subsets in the lung were activated. In addition, chest blast exposure resulted in impaired spatial learning and memory ability, disruption of the blood-brain barrier (BBB), and the expression of Tau, p-tau, S100β and choline acetyltransferase were increased. The results indicated that genetic knockdown of CD28 could inhibit inflammatory cell infiltration, as well as the activation of CD3+ T cells, CD4+ and CD8+ T cell subsets in the lung, improve spatial learning and memory ability, and ameliorate BBB disruption and hippocampal neuron damage. Moreover, genetic knockdown of CD28 could reduce the expression of p-PI3K, p-AKT and NF-κB. In conclusion, chest blast exposure could lead to bTBI, and attenuate bTBI via the PI3K/AKT/NF-κB signaling pathway in male mice. This study provides new targets for the prevention and treatment of veterans with bTBI.