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Abstract Obesity, a growing global health concern, is closely linked to depression. However, the neural mechanism of association between obesity and depression remains poorly understood. In this study, neural‐specific WFS1 deficiency exacerbates the vicious cycle of obesity and depression in mice fed a high‐fat diet (HFD), positioning WFS1 as a crucial factor in this cycle. Through human pluripotent stem cells (hESCs) neural differentiation, it is demonstrated that WFS1 regulates Zn2+ homeostasis and the apoptosis of neural progenitor cells (NPCs) and cerebral organoids by inhibiting the zinc transporter ZnT3 under the situation of dysregulated lipid metabolism. Notably, riluzole regulates ZnT3 expression to maintain zinc homeostasis and protect NPCs from lipotoxicity‐induced cell death. Importantly, riluzole, a therapeutic molecule targeting the nervous system, in vivo administration prevents HFD‐induced obesity and associated depression. Thus, a WFS1‐ZnT3‐Zn2+ axis critical is demonstrated for the vicious cycle of obesity and depression and that riluzole may have the potential to reverse this process against obesity and depression.

BackgroundProstate cancer (PCa) is the second most prevalent malignancy among men globally. The diagnosis, treatment, and prognosis of prostate cancer frequently fall short of expectations. In recent years, the connection between inflammation and prostate cancer has attracted considerable attention. However, there is a lack of bibliometric studies analyzing the research on inflammation within the domain of prostate cancer.Research methodsWe utilized the Web of Science Core Collection (WOSCC) as our data source to extract articles and reviews related to inflammation in prostate cancer, published up until April 12, 2024. The collected data underwent meticulous manual screening, followed by bibliometric analysis and visualization using the Biblioshiny package in R.ResultsThis study encompasses an analysis of 2,786 papers focusing on inflammation-related research within the realm of prostate cancer. Recent years have seen a significant proliferation of publications in this area, with the United States and China being the foremost contributors. The most prolific author in this domain is Demarzoam, with Johns Hopkins University standing out as the most influential institution. The leading journal in disseminating these studies is PROSTATE. Keyword co-occurrence analysis reveals that ‘inflammation-related biomarkers’, ‘inflammation index’, and ‘tumor immune microenvironment’ represent the current research hotspots and frontiers.ConclusionThe findings of this bibliometric study serve to illuminate the current landscape of inflammation-related research in the field of prostate cancer, while further augmenting the discourse on inflammation-mediated cancer therapeutics. Of particular note is the potential of these discoveries to facilitate a more nuanced understanding among researchers regarding the interplay between inflammation and prostate cancer.

Background Antineoplastic chemotherapies are dramatically efficient when they provoke immunogenic cell death (ICD), thus inducing an antitumor immune response and even tumor elimination. However, activated caspases, the hallmark of most cancer chemotherapeutic agents, render apoptosis immunologically silent. Whether they are dispensable for chemotherapy-induced cell death and the apoptotic clearance of cells in vivo is still elusive.Methods A rational cell-based anticancer drug library screening was performed to explore the immunogenic apoptosis pathway and therapeutic targets under apoptotic caspase inhibition. Based on this screening, the potential of caspase inhibition in enhancing chemotherapy-induced antitumor immunity and the mechanism of actions was investigated by various cells and mouse models.Results Heat shock protein 90 (Hsp90) inhibition activates caspases in tumor cells to produce abundant genomic and mitochondrial DNA fragments and results in cell apoptosis. Meanwhile, it hijacks Caspase-9 signaling to suppress intrinsic DNA sensing. Pharmacological blockade or genetic deletion of Caspase-9 causes tumor cells to secrete interferon (IFN)-β via tumor intrinsic mitochondrial DNA/the second messenger cyclic GMP–AMP (cGAS) /stimulator of interferon genes (STING) pathway without impairing Hsp90 inhibition-induced cell death. Importantly, both Caspase-9 and Hsp90 inhibition triggers an ICD, leading to the release of numerous damage-associated molecular patterns such as high-mobility group box protein 1, ATP and type I IFNs in vitro and remarkable antitumor effects in vivo. Moreover, the combination treatment also induces adaptive resistance by upregulating programmed death-ligand 1 (PD-L1). Additional PD-L1 blockade can further overcome this acquired immune resistance and achieve complete tumor regression.Conclusions Blockade of Caspase-9 signaling selectively provokes Hsp90-based chemotherapy-mediated tumor innate sensing, leading to CD8+ T cell-dependent tumor control. Our findings implicate that pharmacological modulation of caspase pathway increases the tumor-intrinsic innate sensing and immunogenicity of chemotherapy-induced apoptosis, and synergizes with immunotherapy to overcome adaptive resistance.

Abstract The main challenge of Multiple Object Tracking (MOT) is that there is great uncertainty in data association when using the tracked predicted values and tracked trajectories. Meanwhile, the MOT is complex and time‐consuming. When equipment resources are limited or real‐time requirement is high, its application is very limited. Therefore, we propose a Lightweight Deep Appearance Embedding (LDAE) to assist the association of trajectories. Firstly, in addition to motion information in data association, we also introduce more discriminative appearance features to participate in the affinity measure to effectively distinguish similar targets. Secondly, according to the idea of feature mapping, we design a lightweight deep appearance embedding module. It can help extract appearance features with less computation. Finally, we propose a simulated occlusion strategy for the training of the LDAE, which helps improve the ability to recognise different targets in dense scenes. The LDAE dramatically reduces the computational cost and improves the accuracy of data association. Extensive experiments are conducted on the MOT datasets (MOT16, MOT17 and MOT20), which prove that the LDAE outperforms several state‐of‐the‐art trackers in the tracking accuracy and anti‐occlusion performance. Furthermore, we apply the LDAE to escalators, which can achieve fast and stable tracking effect.

Immature function and fragility hinder application of hESC-derived β cells (SC-β cell) for diabetes cell therapy. Here, the authors identify ZnT8 as a gene editing target to enhance the insulin secretion and cell survival under metabolic stress by abolishing zinc transport in SC-β cells.

BackgroundThis study aimed to establish an effective model for preoperative prediction of tumor deposits (TDs) in patients with rectal cancer (RC). MethodsIn 500 patients, radiomic features were extracted from magnetic resonance imaging (MRI) using modalities such as high-resolution T2-weighted (HRT2) imaging and diffusion-weighted imaging (DWI). Machine learning (ML)-based and deep learning (DL)-based radiomic models were developed and integrated with clinical characteristics for TD prediction. The performance of the models was assessed using the area under the curve (AUC) over five-fold cross-validation.ResultsA total of 564 radiomic features that quantified the intensity, shape, orientation, and texture of the tumor were extracted for each patient. The HRT2-ML, DWI-ML, Merged-ML, HRT2-DL, DWI-DL, and Merged-DL models demonstrated AUCs of 0.62 ± 0.02, 0.64 ± 0.08, 0.69 ± 0.04, 0.57 ± 0.06, 0.68 ± 0.03, and 0.59 ± 0.04, respectively. The clinical-ML, clinical-HRT2-ML, clinical-DWI-ML, clinical-Merged-ML, clinical-DL, clinical-HRT2-DL, clinical-DWI-DL, and clinical-Merged-DL models demonstrated AUCs of 0.81 ± 0.06, 0.79 ± 0.02, 0.81 ± 0.02, 0.83 ± 0.01, 0.81 ± 0.04, 0.83 ± 0.04, 0.90 ± 0.04, and 0.83 ± 0.05, respectively. The clinical-DWI-DL model achieved the best predictive performance (accuracy 0.84 ± 0.05, sensitivity 0.94 ± 0. 13, specificity 0.79 ± 0.04).ConclusionsA comprehensive model combining MRI radiomic features and clinical characteristics achieved promising performance in TD prediction for RC patients. This approach has the potential to assist clinicians in preoperative stage evaluation and personalized treatment of RC patients.

ObjectiveRed blood cell (RBC) parameters are associated with outcomes following aneurysmal subarachnoid hemorrhage (aSAH), but their predictive value remains uncertain. This study aimed to detect the association between RBC parameters and functional outcome in aSAH patients undergoing surgical clipping.MethodsThis retrospective observational study included aSAH patients who underwent surgical clipping at Affiliated Hospital of North Sichuan Medical College between August 2016 and September 2019. The functional outcome following aSAH was assessed by modified Rankin Scale (mRS), and mRS 3–6 was defined as poor functional outcome.ResultsOut of 187 aSAH patients included (62% female, 51–66 years old), 73 patients had poor functional outcome. Multivariate logistic regression of admission parameters showed that World Federation of Neurosurgical Societies (WFNS) grade (odds ratio [95% CI]: 1.322 [1.023–1.707], p = 0.033) and white blood cell (WBC) (odds ratio [95% CI]: 1.136 [1.044–1.236], p = 0.003) were independently associated with poor functional outcome. In postoperative parameters, RBC distribution width (RDW) (odds ratio [95% CI]: 1.411 [1.095–1.818], p = 0.008), mean platelet volume (MPV, odds ratio [95% CI]: 1.253 [1.012–1.552], p = 0.039) and admission WFNS grade (odds ratio [95% CI]: 1.439 [1.119–1.850], p = 0.005) were independently associated with poor functional outcome. The predictive model including WFNS grade, admission WBC, and postoperative RDW and MPV had significantly higher predictive power compared to WFNS grade alone (0.787 [0.722–0.852] vs. 0.707 [0.630–0.784], p = 0.024). The combination of WFNS grade and WBC on admission showed the highest positive predictive value (75.5%) and postoperative RDW and MPV combined with admission WFNS grade and WBC showed the highest negative predictive value (83.7%).ConclusionPostoperative RDW is independently associated with poor functional outcome in aSAH patients undergoing surgical clipping. A combined model containing postoperative RDW may help predict good outcome in patients with aSAH after timely aneurysm clipping.

Obesity-related muscular dysfunction and relative muscle atrophy affect an increasing number of people. Elucidating the molecular mechanisms of skeletal muscle cell development and growth may contribute to the maintenance of skeletal muscle mass in obesity. Fatty acid translocase (FAT/CD36), as a long-chain fatty acid transport protein, is crucial for lipid metabolism and signaling. CD36 is known to function in myogenic differentiation, and whether it affects the proliferation of skeletal muscle cells and the underlying mechanisms remain unclear. In this study, the effect of CD36 deficiency on skeletal muscle cell viability and proliferation was examined using C2C12 myoblasts. Results showed that the deletion of CD36 enhanced the inhibitory effect of PA on the proliferation and the promotion of apoptosis in skeletal muscle cells. Intriguingly, the silencing of CD36 suppressed cell proliferation by preventing the cell cycle from the G0/G1 phase to the S phase in a cyclin D1/CDK4-dependent manner. Overall, we demonstrated that CD36 was involved in skeletal muscle cell proliferation by cell cycle control, and these findings might facilitate the treatment of obesity-related muscle wasting.

Functional materials with high viscosity and solid materials have received more and more attentions in flexible pressure sensors, which are inadequate in the most used molding method. Herein, laser direct writing (LDW) method is proposed to fabricate flexible piezoresistive sensors with microstructures on PDMS/ MWCNTs composites with an 8% MWCNTs mass fraction. By controlling laser energy, microstructures with different geometries can be obtained, which significantly impacts the performances of the sensors. Subsequently, curved microcones with excellent performance are fabricated under parameters of f = 40 kHz and v = 150 mm·s-1. The sensor exhibits continuous multi-linear sensitivity, ultrahigh original sensitivity of 21.80 % kPa-1, wide detection range of over 20 kPa, response/recovery time of ~100 ms and good cycle stability for more than 1000 times. Besides, obvious resistance variation can be observed when tiny pressure (a peanut of 30 Pa) is applied. Finally, the flexible piezoresistive sensor can be applied for LED brightness controlling, pulse detection and voice recognition.

During gait rehabilitation training， patients with hemiplegia or stroke are prone to muscle cramps， which can cause them to lose their balance due to their inability to support their weight and cause secondary injuries. In response to the above problems， a six-degree-of-freedom parallel rehabilitation robot driven by eight cables is designed， which can not only perform gait training on patients but also implement effective anti-fall protection for patients. Firstly， the configuration of the robot is described， and its kinematics model is established by using the closed vector quadrilateral method. Secondly， combined with the characteristics of cable-driven， a concept of a robot force control workspace and its solution method are proposed based on the statics analysis. In order to avoid secondary injuries to patients after losing their balance， a space trajectory safety wall is further proposed based on the force-controlled working space， which classified the possible shapes to be protected for patients and studied the space trajectory path planning method for their return to the safety wall. Finally， two different types of to-be-protected profiles are selected to study the changes in cable length and tension as they moved along the regression trajectory which verified the effectiveness and rationality of the trajectory planning method for the return safety wall.

The possible role of fatty acid translocase (CD36) in the treatment of obesity has gained increasing research interest since researchers recognized its coordinated function in fatty acid uptake and oxidation. However, the effect of CD36 deficiency on intracellular insulin signaling is complex and its impact may depend on different nutritional stresses. Therefore, we investigated the various effects of CD36 deletion on insulin signaling in C2C12 myotubes with or without palmitic acid (PA) overload. In the present work, we reported the upregulated expression levels of CD36 in the skeletal muscle tissues of obese humans and mice as well as in C2C12 myotubes with PA stimulation. CD36 knockdown using RNA interference showed that insulin signaling was impaired in CD36-deficient C2C12 cells in the absence of PA loading, suggesting that CD36 is essential for the maintenance of insulin action, possibly resulting from increased mitochondrial dysfunction and endoplasmic reticulum (ER) stress; however, CD36 deletion improved insulin signaling in the presence of PA overload due to a reduction in lipid overaccumulation. In conclusion, we identified differential roles of CD36 in regulating muscle insulin response under conditions with and without PA overload, which provides supportive evidence for further research into therapeutic approaches to diabetes.

Abstract Background Liver fibrosis and fibrosis‐related hepatocarcinogenesis are a rising cause for morbidity and death worldwide. Although transforming growth factor‐β (TGF‐β) is a critical mediator of chronic liver fibrosis, targeting TGF‐β isoforms and receptors lead to unacceptable side effect. This study was designed to explore the antifibrotic effect of Compound kushen injection (CKI), an approved traditional Chinese medicine formula, via a therapeutic strategy of rebalancing TGF‐β/Smad7 signaling. Methods A meta‐analysis was performed to evaluate CKI intervention on viral hepatitis‐induced fibrosis or cirrhosis in clinical randomized controlled trials (RCTs). Mice were given carbon tetrachloride (CCl4) injection or methionine‐choline deficient (MCD) diet to induce liver fibrosis, followed by CKI treatment. We examined the expression of TGF‐β/Smad signaling and typical fibrosis‐related genes in hepatic stellate cells (HSCs) and fibrotic liver tissues by qRT‐PCR, Western blotting, RNA‐seq, immunofluorescence, and immunohistochemistry. Results Based on meta‐analysis results, CKI improved the liver function and relieved liver fibrosis among patients. In our preclinical studies by using two mouse models, CKI treatment demonstrated promising antifibrotic effects and postponed hepatocarcinogenesis with improved liver function and histopathologic features. Mechanistically, we found that CKI inhibited HSCs activation by stabilizing the interaction of Smad7/TGF‐βR1 to rebalance Smad2/Smad3 signaling, and subsequently decreased the extracellular matrix formation. Importantly, Smad7 depletion abolished the antifibrotic effect of CKI in vivo and in vitro. Moreover, matrine, oxymatrine, sophocarpine, and oxysophocarpine were identified as material basis responsible for the antifibrosis effect of CKI. Conclusions Our results unveil the approach of CKI in rebalancing TGF‐β/Smad7 signaling in HSCs to protect against hepatic fibrosis and hepatocarcinogenesis in both preclinical and clinical studies. Our study suggests that CKI can be a candidate for treatment of hepatic fibrosis and related oncogenesis.

This work aims to develop and techno-economically analyze a novel coal-based polygeneration process of Molten Carbonate Fuel Cell (MCFC) and methane synthesis with a waste heat recovery system. In this process, the unshifted syngas without entering Rectisol is directly mixed with a part of H2-rich syngas to reduce the energy consumption of Rectisol and flexibly adjust the H/C ratio. An extended Duran-Grossmann (D-G) model for waste heat recovery steam cycle optimization is proposed by conducting Heat Integration among the whole process. According to techno-economic analysis, the annual capital cost of the proposed system is 50,006,000 $, the overall exergy efficiency is 56.3 %. Compared with the base plant, the MCFC with power generation of 16.98 MW is applied instead of the Rankine cycle (RC), which results in a 14 % increase in the efficiency of the power generation system. The major contributions derived from this work are of significant aid in highlighting strong potentials for overall performance enhancement via polygeneration optimization.

Compared with direct utilisation as fuel, the downstream processing of shale gas shows great potential in economic competitiveness, in which methanol is a particularly important product. This study simulates a technical route for producing methanol from shale gas, which is evaluated from the points of economic, exergy and environment. The economic target is estimated by purchased cost curves, while exergy analysis demonstrates the distribution of exergy destruction. A hybrid LCI (Life cycle inventory) model is established to assess pollutant emissions by sources. The results show that methane reforming features the highest capital cost, while methanol synthesis requires the highest operating cost. The reaction systems account for 73.3 % of total exergy destruction. Electricity consumption dominates the environmental impacts of the whole process.

As a sort of emerging unconventional energy, shale gas has extensive market outlook by virtue of its enormous reserves, and concerns for shale gas exploitation and processing have been raised nowadays. Raw shale gas must be processed to achieve certain specifications before it can be transmitted in pipelines or utilized by consumers. Sweetening is a gas conditioning process to decrease the concentration of acid gases such as hydrogen sulfide and carbon dioxide which are not preferred in sales gas in consideration of heating value specification and corrosion prevention. However, the after-treatment of acid gases is not discussed in many research of sweetening process. In this paper, a flowsheet of shale gas sweetening process is established using Aspen Plus v8.6. Dissolution of light gases and weak electrolyte, absorption of acid gases and reactions in electrolyte solution are considered simultaneously in process modelling. Diethanolamine (DEA) solution is employed as the solvent to separate acid gases from raw shale gas. The optimal feed stage of rich solvent regeneration and reflux ratio of regenerator are analysed to optimize the sweetening flowsheet. A three-stage Claus process is simulated coupling with shale gas sweetening process to convert hydrogen sulfide in acid gas to element sulphur for pollution reduction. A principle is proposed to determine the operating temperature of each Claus reactor which is a decisive parameter on sulfur recovery efficiency and performance of Claus process. Ultimately, the sulfur recovery efficiency of the three-stage Claus process proposed in this paper is 97.35 %. The effectivity of the principle is confirmed by the results reported in literatures. Energy synthesis is then adopted to integrate sweetening process with Claus process in both mass and energy flow. The coupled process provides with more streams than a single sweetening or Claus process, promoting the reasonability of energy utilization. Streams are extracted and matched for heat exchanger network (HEN) synthesis to reduce the energy consumption and total annual cost of the whole process.

In the brain, the serotonergic neurons located in the raphe nucleus are the unique resource of the neurotransmitter serotonin, which plays a pivotal role in the regulation of brain development and functions. Dysfunction of the serotonin system is present in many psychiatric disorders. Lack of in vitro functional human model limits the understanding of human central serotonergic system and its related diseases and clinical applications. Previously, we have developed a method generating human serotonergic neurons from induced pluripotent stem cells (iPSCs). In this study, we analyzed the features of these human iPSCs-derived serotonergic neurons both in vitro and in vivo. We found that these human serotonergic neurons are sensitive to the selective neurotoxin 5, 7-Dihydroxytryptamine (5,7-DHT) in vitro. After being transplanted into newborn mice, the cells not only expressed their typical molecular markers, but also showed the migration and projection to the host’s cerebellum, hindbrain and spinal cord. The data demonstrate that these human iPSCs-derived neurons exhibit the typical features as the serotonergic neurons in the brain, which provides a solid foundation for studying on human serotonin system and its related disorders.

Direct lineage conversion of adult cells is a promising approach for regenerative medicine. A major challenge of lineage conversion is to generate specific cell subtypes. The pancreatic islets contain three major hormone-secreting endocrine subtypes: insulin+ β-cells, glucagon+ α-cells, and somatostatin+ δ-cells. We previously reported that a combination of three transcription factors, Ngn3, Mafa, and Pdx1, directly reprograms pancreatic acinar cells to β-cells. We now show that acinar cells can be converted to δ-like and α-like cells by Ngn3 and Ngn3+Mafa respectively. Thus, three major islet endocrine subtypes can be derived by acinar reprogramming. Ngn3 promotes establishment of a generic endocrine state in acinar cells, and also promotes δ-specification in the absence of other factors. δ-specification is in turn suppressed by Mafa and Pdx1 during α- and β-cell induction. These studies identify a set of defined factors whose combinatorial actions reprogram acinar cells to distinct islet endocrine subtypes in vivo.

During programmed cell death, apoptotic cells are recognized and rapidly engulfed by phagocytes. Although a number of genes have been identified that promote cell corpse engulfment, it is not well understood how phagocytosis of apoptotic cells is negatively regulated. Here we have identified Caenorhabditis elegans myotubularin MTM-1 as a negative regulator of cell corpse engulfment. Myotubularins (MTMs) constitute a large, highly conserved family of lipid phosphatases. MTM gene mutations are associated with various human diseases, but the cellular functions of MTM proteins are not clearly defined. We found that inactivation of MTM-1 caused significant reduction in cell corpses in strong loss-of-function mutants of ced-1, ced-6, ced-7, and ced-2, but not in animals deficient in the ced-5, ced-12, or ced-10 genes. In contrast, overexpression of MTM-1 resulted in accumulation of cell corpses. This effect is dependent on the lipid phosphatase activity of MTM-1. We show that loss of mtm-1 function accelerates the clearance of cell corpses by promoting their internalization. Importantly, the reduction of cell corpses caused by mtm-1 RNAi not only requires the activities of CED-5, CED-12, and CED-10, but also needs the functions of the phosphatidylinositol 3-kinases (PI3Ks) VPS-34 and PIKI-1. We found that MTM-1 localizes to the plasma membrane in several known engulfing cell types and may modulate the level of phosphatidylinositol 3-phosphate (PtdIns(3)P) in vivo. We propose that MTM-1 negatively regulates cell corpse engulfment through the CED-5/CED-12/CED-10 module by dephosphorylating PtdIns(3)P on the plasma membrane.

BACKGROUND:The serine/threonine kinase BUB1 (Budding Uninhibited by Benzimidazole 1) was originally identified in yeast as a checkpoint protein, based on its mutant's incapacity of delaying the cell cycle in response to loss of microtubules. Our understanding of its function is primarily from studies carried out in yeast S. cerevisiae. It has been shown that it is a component of the mitotic spindle checkpoint and regulates the separation of sister chromatids through its downstream molecules. However, its roles in multi-cellular organisms remain unclear. METHODS AND FINDINGS:In nematode C. elegans, rapid cell divisions primarily occur in embryos and in germline of postembryonic larvae and adults. In addition, a select set of cells undergo a few rounds of cell division postembryonically. One common phenotype associated with impaired cell division is described as Stu (Sterile and Uncoordinated) [1], [2]. We conducted a genetic screen for zygotic mutants that displayed Stu phenotype in C. elegans. We isolated seven Stu mutants that fell into five complementation groups. We report here that two mutations, FanWang5 (fw5) and FanWang8 (fw8) affect the bub-1 gene, a homolog of yeast BUB1. Both mutant alleles of fw5 and fw8 exhibited variable behavioral defects, including developmental arrest, uncoordination and sterility. The number of postembryonically born neurons in the ventral cord decreased and their axon morphology was abnormal. Also, the decrease of neurons in the ventral cord phenotype could not be suppressed by a caspase-3 loss-of-function mutant. In addition, bub-1(fw5 and fw8) mutants showed widespread effects on postembryonic development in many cell lineages. We found that bub-1 functioned maternally in several developmental lineages at the embryonic stage in C. elegans. Studies in yeast have shown that BUB1 functions as a spindle checkpoint protein by regulating the anaphase promoting complex/cyclosome (APC/C). We performed double mutant analysis and observed that bub-1 genetically interacted with several downstream genes, including fzy-1/CDC20, mat-2/APC1 and emb-27/APC6. CONCLUSIONS:Our results demonstrate a conserved role of bub-1 in cell-cycle regulation and reveal that C. elegans bub-1 is required both maternally and zygotically. Further, our genetic analysis is consistent with that the function of bub-1 in C. elegans is likely similar to its yeast and mammalian homologs.

Abstract Background Psoriasis is a chronic inflammatory skin disorder associated with various comorbidities. The role of nutrition and dietary antioxidants in psoriasis management has gained attention. The Composite Dietary Antioxidant Index (CDAI) quantifies overall dietary antioxidant intake, but its association with psoriasis remains unclear. This study aimed to investigate the association between the CDAI and psoriasis, as well as the relationship between individual components of CDAI and psoriasis risk. Methods Data from the US National Health and Nutrition Examination Survey (NHANES) were analyzed. Baseline characteristics, CDAI scores, and psoriasis status were assessed. Multivariable logistic regression and restricted cubic splines were employed to analyze the association. Results The study included 23,311 participants, with 621 diagnosed with psoriasis. Higher CDAI scores were associated with a lower odds ratio (OR) of psoriasis occurrence (OR = 0.72, 95% CI 0.56–0.92, P = 0.009 in Model 3). Vitamin E intake exhibited an inverse correlation with psoriasis risk (OR = 0.76, 95% CI 0.60–0.96, P = 0.039 in Model 3). Other CDAI components did not show significant associations with psoriasis. Conclusion This study demonstrates a significant inverse association between CDAI and psoriasis, indicating that higher dietary antioxidant intake is associated with a reduced risk of psoriasis. Specifically, higher vitamin E intake was associated with a lower likelihood of psoriasis. These findings underscore the potential role of dietary antioxidants in psoriasis management. Further research is warranted to elucidate the underlying mechanisms and explore targeted dietary interventions.

Abstract Background Optimal blood pressure (BP) levels to reduce the long-term risk of cognitive decline remains controversial. We aimed to investigate the association between BP and anti-hypertensive treatment status with cognitive decline in older adults. Methods This study used data from the China Health and Retirement Longitudinal Study. Cognitive function was assessed at year 2011, 2013, 2015, and 2018. Global cognitive Z-score was calculated as the average score of episodic memory and mental intactness. BP were measured at the first and second wave. Pulse pressure (PP) was calculated as systolic BP (SBP) minus diastolic BP. Cumulative BP was calculated as the area under the curve using BP measurements from 2011 to 2013. Linear mixed models were used to assess the longitudinal association between BP-related measurements and cognitive decline. Results We included 11,671 participants (47.3% men and mean age 58.6 years). Individual with BP > 140/90 mm Hg or taking anti-hypertensive medication were independently associated with accelerated cognitive decline (β=-0.014, 95% CI: -0.020 to -0.007). Individuals with anti-hypertensive medication use, but with controlled SBP to less than 120 mm Hg did not have a significantly increased risk of cognitive decline compared with normotension (β=-0.003, 95% CI: -0.021 to 0.014). Individuals on anti-hypertensive treatment with PP of more than 70 mm Hg had a significantly higher risk of cognitive decline (β=-0.033, 95% CI: -0.045 to -0.020). Regardless of anti-hypertensive treatment status, both elevated baseline and cumulative SBP and PP were found to be independently associated with accelerated cognitive decline. Conclusions Cumulatively elevated SBP, PP and uncontrolled BP were associated with subsequent cognitive decline. Effectively controlling BP with anti-hypertensive treatment may be able to preserve cognitive decline in older adults.

Candida albicans is an opportunistic fungal pathogen known for surviving in various nutrient-limited conditions within the host and causing infections. Our prior research revealed that Hfl1p, an archaeal histone-like or Hap5-like protein, is linked to mitochondrial ATP generation and yeast-hyphae morphogenesis. However, the specific roles of Hfl1p in these virulence behaviours, through its function in the CBF/NF-Y complex or as a DNA polymerase II subunit, remain unclear. This study explores Hfl1p’s diverse functions in energy metabolism and morphogenesis. By combining proteomic analysis and phenotypic evaluations of the hfl1Δ/hfl1Δ mutant with ChIP data, we found that Hfl1p significantly impacts mitochondrial DNA-encoded CI subunits, the tricarboxylic acid (TCA) cycle, and morphogenetic pathways. This influence occurs either independently or alongside other transcription factors recognizing a conserved DNA motif (TAXXTAATTA). These findings emphasize Hfl1p’s critical role in linking carbon metabolism and mitochondrial respiration to the yeast-to-filamentous form transition, enhancing our understanding of C. albicans’ metabolic adaptability during morphological transition, an important pathogenic trait of this fungus. This could help identify therapeutic targets by disrupting the relationship between energy metabolism and cell morphology in C. albicans.

Introduction This study combined the bioinformatics and in vitro experiment-related technologies to analyze the impact of steroid 5 alpha-reductase 3 (SRD5A3) on the prognosis and immune microenvironment of Liver Hepatocellular Carcinoma (LIHC).Method Gene expression and clinical data were obtained from public databases. The prognosis was evaluated using survival, multifactor Cox, enrichment, and mutation analyses. This was then verified through in vitro experiments.Results The expression level of SRD5A3 in LIHC tissues was significantly higher than that in the adjacent tissues. Kaplan–Meier survival analysis showed that high SRD5A3 expression was associated with poor overall survival (OS) and short progression-free survival in patients with LIHC. Multivariate Cox regression analysis revealed that positive SRD5A3 expression was an independent risk factor for OS in patients with LIHC. Expression of SRD5A3 was negatively correlated with immune cell infiltration of CD4+ T, CD8+ T, and B cells. GO and KEGG enrichment analyses showed that SRD5A3 was significantly enriched in signaling- and tumor metastasis-related pathways. Nomogram and calibration curve showed that the predicted performance of the model was consistent with the actual results. In vitro results confirmed that SRD5A3 knockdown inhibited the migration, invasion, and proliferation of LIHC cells.Conclusions SRD5A3 is actively expressed in LIHC, and positive expression of SRD5A3 is an independent risk factor for different prognoses in patients with LIHC. SRD5A3 can promote the proliferation, migration, and invasion of liver cancer cells and is related to short immune infiltration in patients with LIHC.