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Recent studies on male infertility reveal a growing worry: more infertile men are dealing with inflammation in the testis. Analyzing testicular biopsies from infertile men highlights a significant presence of inflammation. This connection, supported by clinical and pathological evidence, emphasizes that testicular inflammation hampers sperm production, leading to lasting declines in sperm count and quality. However, the exact reasons behind male infertility due to orchitis, a type of testicular inflammation, are still uncertain. Understanding these fundamental aspects of molecular signals and cellular mechanisms in testicular inflammation is crucial. Our review delves into recent literature with a dual objective: elucidating potential mechanisms involving immune cells, non-immune cells, and cytokines that link orchitis to male infertility, while also paving the way for precise interventions and solutions to address the challenges of male infertility.

Abstract Background Chimeric antigen receptor (CAR)-T therapy has emerged as a promising treatment for hematologic malignancies. However, cytopenia remains one of the most frequent and challenging adverse effects of this therapy. Methods We conducted a retrospective analysis of 26 patients with relapsed/refractory aggressive B-cell lymphoma who received CAR-T therapy at our center. Subsequently, to investigate measures to address cytopenias following CAR-T therapy, we isolated and generated murine CAR-T cells and bone marrow-derived mesenchymal stem cells (MSCs), establishing a murine syngeneic CAR-T therapy model. We assessed the impact of MSC infusion on hematopoietic recovery post-CAR-T therapy by evaluating complete blood count, bone marrow hematopoietic stem cells and their subpopulations, bone marrow histomorphology, and hematopoiesis-related genes. Results All patients experienced cytopenias to varying degrees, with complete lineage involvement in half of the patients. Grade ≥ 3 cytopenias were observed in 88.46% of the patients. CAR-T therapy was associated with a higher incidence of biphasic, late-onset, or prolonged cytopenias. Survival analysis indicated that neutropenia and lymphopenia tended to be associated with better prognosis, whereas thrombocytopenia tended to be related to poorer outcomes. Through animal experiments, we discovered that MSCs infusion boosted HSCs and their long-term subpopulations, enhancing hematopoietic recovery, particularly in the megakaryocyte lineage, and mitigating bone marrow damage. Importantly, both in vitro and in vivo experiments demonstrated that MSCs did not compromise the activity or antitumor efficacy of CAR-T cells. Conclusions Our findings propose MSCs infusion as a promising strategy to address cytopenias, particularly thrombocytopenia, after CAR-T therapy. This approach could help overcome certain limitations of cellular immunotherapy by enhancing hematopoietic recovery without compromising the efficacy of CAR-T cells. Highlights 1 Cytopenia is a frequently observed adverse effect following CAR-T therapy, and it is often characterized by biphasic and prolonged patterns. 2 MSCs play a critical role in promoting hematopoietic recovery and mitigating bone marrow damage in a murine model of CAR-T therapy 3 The activity and antitumor efficacy of CAR-T cells were not impaired by MSCs. Graphical Abstract

Abstract Dementia represents a significant global health challenge, with early screening during the preclinical stage being crucial for effective management. Traditional diagnostic biomarkers for Alzheimer’s Disease, the most common form of dementia, are limited by cost and invasiveness. Mild cognitive impairment (MCI), a precursor to dementia, is currently identified through neuropsychological tests like the Montreal Cognitive Assessment (MoCA), which are not suitable for large-scale screening. Eye-tracking technology, capturing and quantifying eye movements related to cognitive behavior, has emerged as a promising tool for cognitive assessment. Subtle changes in eye movements could serve as early indicators of MCI. However, the interpretation of eye-tracking data is challenging. This study introduced a dementia screening tool, VR Eye-tracking Cognitive Assessment (VECA), using eye-tracking technology, machine learning, and virtual reality (VR) to offer a non-invasive, efficient alternative capable of large-scale deployment. VECA was conducted with 201 participants from Shenzhen Baoan Chronic Hospital, utilizing eye-tracking data captured via VR headsets to predict MoCA scores and classify cognitive impairment across different educational backgrounds. The support vector regression model employed demonstrated a high correlation (0.9) with MoCA scores, significantly outperforming baseline models. Furthermore, it established optimal cut-off scores for identifying cognitive impairment with notable sensitivity (88.5%) and specificity (83%). This study underscores VECA’s potential as a portable, efficient tool for early dementia screening, highlighting the benefits of integrating eye-tracking technology, machine learning, and VR in cognitive health assessments.

Abstract Background Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a rare cause of heart attack, which may not receive sufficient attention from patients during post-discharge treatment, especially among those with normal coronary angiography results. Case presentation We present the case of a 65-year-old woman who was readmitted to the hospital with ventricular septal rupture (VSR) complicated by ventricular aneurysm, occurring 2 weeks after myocardial infarction. During the initial admission, coronary angiography revealed normal coronary arteries, leading to a diagnosis of MINOCA. Epicardial coronary vasospasm or coronary embolism was considered as potential causes; however, the patient did not adhere to standardized treatment upon initial discharge. The delayed VSR led to a decline in cardiac function but did not result in severe hemodynamic impairment. Following correction of heart failure with medications, the patient underwent percutaneous VSR repair 19 days after diagnosis and was discharged with a favorable recovery. Conclusions The occurrence of delayed VSR complicated with ventricular aneurysm in patients with MINOCA is rare, highlighting the possibility of serious complications in MINOCA cases. Both cardioprotective therapies and cause-targeted therapies are essential in the management of patients with MINOCA.

Abstract Background and Objective Klotho is a protein that is closely related to human aging. Soluble Klotho (S-Klotho) is a circulating protein, and its level decreases in response to systemic inflammation. The relationship between the platelet/high-density lipoprotein cholesterol ratio (PHR), an emerging inflammatory index, and S-Klotho concentrations is still unclear. In addition, the mean platelet volume has been confirmed to have a significant negative association with S-Klotho concentrations, but the relationship between the platelet count (PC) and S-Klotho concentrations has not yet been reported. Methods Data from individuals who participated in the National Health and Nutrition Examination Survey (NHANES) during the five cycles from 2007 to 2016 were retrieved for analysis. Linear regression, two-piecewise linear regression, and restricted cubic spline (RCS) methods were used to analyze the associations of the PHR index and its components with S-Klotho concentrations. In addition, subgroup analysis and effect modification tests were conducted. Results A total of 11,123 participants (5463 men (48.17%)), with an average age of 56.2 years, were included. After full adjustment, the S-Klotho levels of participants in the highest quartile group of PHR (β: -51.19, 95% CI: -75.41 to -26.97, P

Abstract Plastic pollution is an emerging environmental issue, with microplastics and nanoplastics raising health concerns due to bioaccumulation. This work explored the impact of polystyrene nanoparticle (PS-NPs) exposure during prepuberty on male reproductive function post maturation in rats. Rats were gavaged with PS-NPs (80 nm) at 0, 3, 6, 12 mg/kg/day from postnatal day 21 to 95. PS-NPs accumulated in the testes and reduced sperm quality, serum reproductive hormones, and testicular coefficients. HE staining showed impaired spermatogenesis. PS-NPs disrupted the blood-testis barrier (BTB) by decreasing junction proteins, inducing inflammation and apoptosis. Transcriptomics identified differentially expressed genes related to metabolism, lysosome, apoptosis, and TLR4 signaling. Molecular docking revealed Cordycepin could compete with polystyrene for binding to TLR4. Cordycepin alleviated oxidative stress and improved barrier function in PS-NPs treated Sertoli cells. In conclusion, prepubertal PS-NPs exposure induces long-term reproductive toxicity in male rats, likely by disrupting spermatogenesis through oxidative stress and BTB damage. Cordycepin could potentially antagonize this effect by targeting TLR4 and warrants further study as a protective agent. This study elucidates the mechanisms underlying reproductive toxicity of PS-NPs and explores therapeutic strategies.

Abstract Background Rating scales and linear indices of surface electromyography (sEMG) cannot quantify all neuromuscular conditions associated with ankle-foot dysfunction in hemiplegic patients. This study aimed to reveal potential neuromuscular conditions of ankle-foot dysfunction in hemiplegic patients by nonlinear network indices of sEMG. Methods Fourteen male patients with hemiplegia and 10 age- and sex-matched healthy male adults were recruited and tested in static standing position. The characteristics of the root mean square (RMS), median frequency (MF), and three nonlinear indices, the clustering coefficient (C), the average shortest path length (L), and the degree centrality (DC), of eight groups of muscles in bilateral calves were observed. Results Compared to those of the control group, the RMS of the medial gastrocnemius (MG), flexor digitorum longus (FDL), and extensor digitorum longus (EDL) on the affected side were significantly lower (P

Abstract Accurate diagnosis of white blood cells from cytopathological images is a crucial step in evaluating leukaemia. In recent years, image classification methods based on fully convolutional networks have drawn extensive attention and achieved competitive performance in medical image classification. In this paper, we propose a white blood cell classification network called ResNeXt-CC for cytopathological images. First, we transform cytopathological images from the RGB color space to the HSV color space so as to precisely extract the texture features, color changes and other details of white blood cells. Second, since cell classification primarily relies on distinguishing local characteristics, we design a cross-layer deep-feature fusion module to enhance our ability to extract discriminative information. Third, the efficient attention mechanism based on the ECANet module is used to promote the feature extraction capability of cell details. Finally, we combine the modified softmax loss function and the central loss function to train the network, thereby effectively addressing the problem of class imbalance and improving the network performance. The experimental results on the C-NMC 2019 dataset show that our proposed method manifests obvious advantages over the existing classification methods, including ResNet-50, Inception-V3, Densenet121, VGG16, Cross ViT, Token-to-Token ViT, Deep ViT, and simple ViT about 5.5–20.43% accuracy, 3.6–23.56% F1-score, 3.5–25.71% AUROC and 8.1–36.98% specificity, respectively.

Abstract Hailstorms, characterized by their intensity, are often accompanied by strong winds and heavy rain, posing significant destructive potential. Data indicate that the economic losses caused by hail to buildings, particularly solar panels, have been increasing annually. However, research on the hail resistance of photovoltaic panels has predominantly focused on the isolated effects of hail impacts and wind loads, neglecting the coupling effects between wind and hail. In this study, a device was designed to couple both wind and hail. The effects of turbulence, hail size, and velocity on hail impact behavior were systematically studied and quantified. A predictive formula for the peak load of hail impact on structures was established. The results indicate that the impact of turbulence on hail is significant. When turbulence intensity varies with hail velocity, hail impact force increases as turbulence decreases and hail velocity increases. When both turbulence and hail diameter vary, the impact force of smaller hailstones shows less variation with increasing turbulence. According to variance analysis, hail velocity is the most significant factor affecting hail impact, followed by hail diameter and finally turbulence. The regression equation is given by $$F = - 0.624I_{{\text{u}}} + 5116.25D + 7.85V_{hail} - 259.709$$ F = - 0.624 I u + 5116.25 D + 7.85 V hail - 259.709 , where $$F$$ F represents the peak impact force in Newtons (N), $$I_{{\text{u}}}$$ I u denotes the turbulence intensity, $$D$$ D is the hail diameter in meters (m), and $$V_{hail}$$ V hail is the hail velocity in meters per second (m/s).

Abstract The Hoek–Brown (H–B) criterion has found widespread application in numerous rock engineering projects. However, its efficacy is compromised by an underestimation of rock strength due to its neglect of the influence of the intermediate principal stress ( $$\sigma_{2}$$ σ 2 ). Experimental evidence underscores the significant impact of $$\sigma_{2}$$ σ 2 . Consequently, there exists an imperative to formulate a three-dimensional (3D) criterion. In this study, a new deviatoric function with two additional parameters ( $$k$$ k and $$A$$ A ) is developed firstly, which ensure compliance with the prerequisites of smoothness and convexity. In addition, the parameters $$k$$ k and $$A$$ A are bonded with the weakening effect of the Lode angle ( $$\theta_{\sigma }$$ θ σ ) and the strengthening effect of the mean stress ( $$\sigma_{m}$$ σ m ), respectively. Then a new 3D strength criterion for rocks is proposed by combining this new deviatoric function and the triaxial compression meridian function of the original H–B criterion. Four distinct sets of test data encompassing various rock types are employed to validate the proposed criterion. The results demonstrate that the proposed criterion adeptly captures the strength characteristics of the four rock types, providing a good depiction of failure surfaces within the 3D principal stress space. Comparative analyses involve the utilization of several existing 3D H–B criteria for strength predictions. The proposed criterion exhibits superior fitting performance for all the selected rocks.

The Anqing section of the Yangtze (Changjiang) River in Anhui Province, China, is one of the most important migratory routes and distribution of the highly valued diadromous estuarine tapertail anchovy Coilia nasus. In the past, this section has suffered a severe loss of C. nasus resources caused by human activities, especially overfishing and water pollution. Since 2019, a fishing ban policy for the species in the Yangtze River has been introduced in China for resource restoration. Otoliths are calcium carbonate structures, and otolith microchemistry can provide detailed life history information that can be used to compare habitat use between different saline water bodies. To study the habitat history of C. nasus in the Anqing section of the Yangtze River after the implementation of the fishing ban, we examined the microchemical characteristics (Sr and Ca) of otoliths from the long (previously named C. ectenes) and short maxillary (previously named C. brachygnathus) types of anchovy using electron probe X-ray microanalysis (EPMA). Line-transect analysis of Sr/Ca ratios suggested that the short maxillary type of C. nasus could be divided into two groups. The otolith Sr/Ca ratios (calculated and expressed as Sr/Ca ×1, 000) of one group were always < 3.0, indicating their freshwater residency. Those of the other group had phases of low (< 3.0, believed to be indicative of a freshwater habitat) and high values (> 3.0, believed to be indicative of a brackish or seawater habitat), indicating that anchovies not only have a freshwater habitat history with low salinity but also a brackish habitat history with high salinity. The latter group of anchovies were typically anadromous C. nasus, as the Sr/Ca ratio of the otoliths of C. nasus fluctuated significantly and coincided with variations between freshwater and estuarine brackish or seawater (i.e., anchovies experienced not only freshwater habitats but also brackish water habitats at different stages of their life history). The Sr content mapping of EPMA with different color patterns for freshwater (blue), brackish water (green-yellow) and seawater (red) habitats also confirmed the results obtained from the line-transect analysis. Our results demonstrated that the population composition of C. nasus in the Anqing section of the Yangtze river became complex, and there was coexistence of freshwater resident and anadromous C. nasus in the Anqing section of the Yangtze River in Anhui Province, China (i.e., freshwater resident and anadromous short maxillary and anadromous long maxillary type C. nasus). This phenomenon may suggest a restoration of C. nasus resource diversity after the implementation of the fishing ban in the Anqing section of the Yangtze River.

Jatropha curcas L. (J. curcas), a shrub plant of the Euphorbiaceae family, has received enormous attention as a promising biofuel plant for the production of biodiesel and medical potential in ethnopharmacology. However, the tumor-promoter toxin phorbol esters present in J. curcas raise concerns for health and environmental risk as its large-scale cultivation limits the use of meal obtained after oil extraction for animal feed. Here, we determined the variation of phorbol ester profiles and contents in eight J. curcas tissues by high-performance liquid chromatography (HPLC) and found phorbol esters present in all parts of the plant except the seed shell. We showed tissue-specific patterns of accumulation of phorbol esters and associated terpenoids at the transcriptional level with high transcript levels in reproductive and young tissues. Genes involved in the same module of terpenoids biosynthesis were positively correlated. We further present diverse abiotic and biotic stresses that had different effects on the accumulation of transcripts in terpenoids shared and branched terpenoid pathways in plant seedlings. The fine-tuning of terpenoids biosynthesis may link with ecological functions in plants under extreme environments and defense against pathogens.

The load-bearing performance (LBP) of pumpable supports (PPS) is crucial for the stability of longwall pre-driven recovery room (PRR) surrounding rock. However, the unbalanced bearing coefficient (UBC)of the PPS (undertaking unequal load along the mining direction) has not been investigated. A mechanical model of the PRR was established, considering the main roof cantilever beam structure, to derive an assessment formula for the load, the failure criteria, and the UBC of the PPS. Subsequently, the generation mechanisms, and influencing factors of the UBC were revealed. Global sensitivity analysis shows that the main roof hanging length (l2) and the spacing between the PPS (r) significantly impact the UBC. A novel design of the PPS and the coupling control technology were proposed and applied to reduce the UBC of the PPS in the adjacent longwall PRR. Monitor results showed no failure of the PPS at the test site, with the UBC (ζ) reduced to 1.1 consistent with the design value (1.15) basically, fully utilizing the collaborative LBP of the PPS. Finally, the maximum roof-to-floor convergence of the PRR was 234 mm, effectively controlling the stability of the surrounding rock of the PRR and ensuring the mining equipment recovery.

In recent years, live streaming has become the mainstream way of online shopping in China. As the dominant player and performer in live streaming, streamers play a crucial role in consumers’ purchase decisions. Therefore, this study focuses on the self-presentation behavior of streamers in the context of e-commerce live streaming and explores the mechanism of its influence on consumers’ purchase intention from the perspective of persuasion knowledge. A total of 538 consumers from China participated in this anonymous survey. The results indicate that helpful and empathetic behaviors of streamers can significantly enhance consumers’ purchase intention, while derogatory, exaggerated, and flattering behaviors of streamers can significantly diminish consumers’ purchase intention. Persuasion knowledge played a mediating role and had a significant negative impact on purchase intention, while anticipated inaction regret weakened its effect on purchase intention.

This umbrella review was conducted aiming to assess the association between genetic variations and the development of diabetic retinopathy (DR) by collecting and evaluating available systematic reviews and meta-analysis results. We evaluated the methodological quality using the Measurement Tool to Assess Systematic Reviews (AMSTAR) 2.0, estimated the summary effect size by using the random effects model and calculated the 95% prediction intervals (PIs). Evidence from the included meta-analyses was graded according to established criteria as follows: convincing, highly suggestive, suggestive, weak, or not significant. This umbrella review included 32 meta-analyses of 52 candidate SNPs. The 12 selected meta-analyses were rated as “high,” 2 studies were rated as “moderate,” 11 studies were graded as “low,” and the remaining 7 studies were graded as “critically low” in terms of methodological quality. Carriers of specific genotypes and alleles of the transcription Factor 7-like 2 C/T (TCF7L2 C/T) polymorphism (rs7903146, p < 0.001) might be more susceptible to the occurrence of DR in the homozygous and recessive models, and these associations were supported by “convincing” evidence. Significant associations were also found between interleukin-6 (IL-6) -174 G/C (rs1800795; p < 0.05) or vascular endothelial growth factor (VEGF) polymorphisms (rs2010963, rs699947, rs1570360, rs2010963, rs699947, rs2146323; all p values

Abstract Background Steroid-induced osteonecrosis of femoral head (SONFH) is a severe health risk, and this study aims to identify immune-related biomarkers and pathways associated with the disease through bioinformatics analysis and animal experiments. Method Using SONFH-related datasets obtained from the GEO database, we performed differential expression analysis and weighted gene co-expression network analysis (WGCNA) to extract SONFH-related genes. A protein-protein interaction (PPI) network was then constructed, and core sub-network genes were identified. Immune cell infiltration and clustering analysis of SONFH samples were performed to assess differences in immune cell populations. WGCNA analysis was used to identify module genes associated with immune cells, and hub genes were identified using machine learning. Internal and external validation along with animal experiments were conducted to confirm the differential expression of hub genes and infiltration of immune cells in SONFH. Results Differential expression analysis revealed 502 DEGs. WGCNA analysis identified a blue module closely related to SONFH, containing 1928 module genes. Intersection analysis between DEGs and blue module genes resulted in 453 intersecting genes. The PPI network and MCODE module identified 15 key targets enriched in various signaling pathways. Analysis of immune cell infiltration showed statistically significant differences in CD8 + t cells, monocytes, macrophages M2 and neutrophils between SONFH and control samples. Unsupervised clustering classified SONFH samples into two clusters (C1 and C2), which also exhibited significant differences in immune cell infiltration. The hub genes (ICAM1, NR3C1, and IKBKB) were further identified using WGCNA and machine learning analysis. Based on these hub genes, a clinical prediction model was constructed and validated internally and externally. Animal experiments confirmed the upregulation of hub genes in SONFH, with an associated increase in immune cell infiltration. Conclusion This study identified ICAM1, NR3C1, and IKBKB as potential immune-related biomarkers involved in immune cell infiltration of CD8 + t cells, monocytes, macrophages M2, neutrophils and other immune cells in the pathogenesis of SONFH. These biomarkers act through modulation of the chemokine signaling pathway, Toll-like receptor signaling pathway, and other pathways. These findings provide valuable insights into the disease mechanism of SONFH and may aid in future drug development efforts.

Abstract The high‐value utilization of blast furnace slag (BFS) and steel slag (SS) as a valuable resource in the field of carbon reduction represents a green revolution, and also is an indispensable path toward breaking through resource and environmental constraints and achieving high‐quality, sustainable development through solid waste utilization in the steel industry. Achieving resource recycling while harnessing the untapped latent energy of resources and exploring their carbon sequestration capabilities has become a crucial avenue for further valorization through waste utilization. BFS and SS discharged from iron‐making or steel‐making furnaces carry a significant amount of latent heat, especially the calcium oxide component in SS, which gives it a unique advantage in the field of comprehensive BFS and SS utilization and carbonation‐based SS utilization. This article discusses the current research status of low‐carbon‐waste‐heat utilization in the production of microcrystalline glass, cementitious materials, functional adsorbents, and other products through front‐end modification of molten BFS and SS. This report also provides an overview of carbon capture by utilizing BFS and SS, offering insights into the research directions for subsequent heat recovery, online quality adjustment, high‐value utilization, and carbon sequestration using BFS and SS in the steel industry.

Abstract Euglena gracilis (E. gracilis), pivotal in the study of photosynthesis, endosymbiosis, and chloroplast development, is also an industrial microalga for paramylon production. Despite its importance, E. gracilis genome exploration faces challenges due to its intricate nature. In this study, we achieved a chromosome-level de novo assembly (2.37 Gb) using Illumina, PacBio, Bionano, and Hi-C data. The assembly exhibited a contig N50 of 619 Kb and scaffold N50 of 1.12 Mb, indicating superior continuity. Approximately 99.83% of the genome was anchored to 46 chromosomes, revealing structural insights. Repetitive elements constituted 58.84% of the sequences. Functional annotations were assigned to 39,362 proteins, enhancing interpretative power. BUSCO analysis confirmed assembly completeness at 80.39%. This first high-quality E. gracilis genome offers insights for genetics and genomics studies, overcoming previous limitations. The impact extends to academic and industrial research, providing a foundational resource.

Abstract Erectile dysfunction (ED) is the most prevalent consequences in men with diabetes mellitus (DM). Recent studies demonstrates that neutrophil extracellular traps (NETs) play important roles in DM and its complications. Nevertheless, whether NETs are involved in ED remains unknown. This work intended to explore the role and mechanisms of NETs in ED in the context of DM. Here, we observed that NET generation and pyroptosis were promoted in DM rats with ED compared with controls. Mechanistically, NETs facilitated NLRP3 inflammasome activation and subsequently triggered pyroptosis under high glucose stress, ultimately leading to ED. Intriguingly, DNase I (a NET degrading agent) alleviated ED and corpus cavernosum injury in DM rats. Overall, NETs might induce ED in DM by promoting NLRP3-mediated pyroptosis in the corpus cavernosum.

Abstract Background Rabies is a fatal zoonotic disease whose pathogenesis has not been fully elucidated, and vaccination is the only effective method for protecting against rabies virus infection. Most inactivated vaccines are produced using Vero cells, which are African green monkey kidney cells, to achieve large-scale production. However, there is a potential carcinogenic risk due to nonhuman DNA contamination. Thus, replacing Vero cells with human diploid cells may be a safer strategy. In this study, we developed a novel 2BS cell-adapted rabies virus strain and analysed its sequence, virulence and immunogenicity to determine its application potential as a human diploid cell inactivated vaccine. Methods and results The 2BS cell-adapted rabies virus strain 2aG4-B40 was established by passage for 40 generations and selection of plaques in 2BS cells. RNA sequence analysis revealed that mutations in 2BS cell-adapted strains were not located at key sites that regulate the production of neutralizing antibodies or virulence in the aG strain (GQ412744.1). The gradual increase in virulence (remaining above 7.0 logLD50/ml from the 40th to 55th generation) and antigen further indicated that these mutations may increase the affinity of the adapted strains for human diploid cells. Identification tests revealed that the 2BS cell-adapted virus strain was neutralized by anti-rabies serum, with a neutralization index of 19,952. PrEP and PEP vaccination and the NIH test further indicated that the vaccine prepared with the 2aG4-B40 strain had high neutralizing antibody levels (2.24 to 46.67 IU/ml), immunogenicity (protection index 270) and potency (average 11.6 IU/ml). Conclusions In this study, a 2BS cell-adapted strain of the 2aG4 rabies virus was obtained by passage for 40 generations. The results of sequencing analysis and titre determination of the adapted strain showed that the mutations in the adaptive process are not located at key sequence regions of the virus, and these mutations may enhance the affinity of the adapted strain for human diploid cells. Moreover, vaccines made from the adapted strain 2aG4-B40 had high potency and immunogenicity and could be an ideal candidate rabies virus strain for inactivated vaccine preparation.

Abstract Pregnane X receptor (PXR) has been reported to regulate glycolipid metabolism. The dysfunction of intestinal barrier contributes to metabolic disorders. However, the role of intestinal PXR in metabolic diseases remains largely unknown. Here, we show that activation of PXR by tributyl citrate (TBC), an intestinal-selective PXR agonist, improves high fat diet (HFD)-induced obesity. The metabolic benefit of intestinal PXR activation is associated with upregulation of β-1,3 galactosyltransferase 5 (B3galt5). Our results reveal that B3galt5 mainly expresses in the intestine and is a direct PXR transcriptional target. B3galt5 knockout exacerbates HFD-induced obesity, insulin resistance and inflammation. Mechanistically, B3galt5 is essential to maintain the integrity of intestinal mucus barrier. B3galt5 ablation impairs the O-glycosylation of mucin2, destabilizes the mucus layer, and increases intestinal permeability. Furthermore, B3galt5 deficiency abolishes the beneficial effect of intestinal PXR activation on metabolic disorders. Our results suggest the intestinal-selective PXR activation regulates B3galt5 expression and maintains metabolic homeostasis, making it a potential therapeutic strategy in obesity.

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

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.

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.