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Abstract Although tamoxifen is commonly utilized as adjuvant therapy for Estrogen Receptor alpha (ERα)-positive breast cancer patients, approximately 30–50% of individuals treated with tamoxifen experience relapse. Therefore, it is essential to investigate additional factors besides ERα that influence the estrogen response. In this study, cross-analysis of databases were performed, and the results revealed a significant association between LINC00626 and ERα signaling as well as increased expression levels of this gene in tamoxifen-resistant cells. LINC00626 is a novel ERα-regulated long non-coding RNA (lncRNA) that has not yet been examined for its potential contribution to endocrine therapy resistance. This study revealed that the upregulation of LINC00626 in breast cancer was associated with poor overall survival in patients. Additionally, ERα signaling was found to transcriptionally regulate LINC00626 expression, thereby promoting cancer progression and enhancing resistance to tamoxifen in breast cancer cells via the regulation of UPF1 expression. Depletion of LINC00626 restored sensitivity to tamoxifen by activating the PERK-ATF4-CHOP signaling pathway via UPF1. These findings support the role of LINC00626 as a potential therapeutic target for combating tamoxifen resistance.

The interaction between prismatic dislocations and a [Formula: see text] twin boundary is systematically investigated using atomistic simulations. Interestingly, when the slip plane is parallel to the plane of shear, the parent prismatic dislocation is transmuted into a prismatic dislocation in the twin while the Burgers vector remains unchanged. In contrast, when the prismatic slip plane is inclined with the plane of shear, the prismatic dislocation is transmuted into the uncommon pyramidal-[Formula: see text] dislocation on the [Formula: see text] plane. The energetics during twin-slip interactions are quantified by Nudged Elastic Band calculations. Our results provide a new understanding in terms of twin-slip interaction in HCP metals.

Non-high-density lipoprotein cholesterol (non-HDL), a more readily available and reliable lipid parameter, is unclear in its association with type 2 diabetes (T2D). Previous studies assessing the relationship between non-HDL and T2D risk remains inconsistent results. We performed a meta-analysis to systematically evaluate this association. The PubMed, EMBASE, Medline, Web of Science, and Cochrane Library databases were systematically searched to find articles on “non-HDL” and “T2D” from inception to December 6, 2023. A random-effects model was used to calculate the effect estimates and 95% confidence intervals. Subgroup analyses and univariate Meta-regression were performed to explore sources of heterogeneity. The main exposure and outcome were non-HDL and T2D, respectively, in the general population. A total of 8 studies included 251,672 participants who met the inclusion criteria for this study. Meta-analysis showed that higher non-HDL increased the risk of T2D compared with the lower non-HDL group (total effect size: 1.16; 95% CI 1.079–1.251, p < 0.001). Subgroup analyses and Meta-regression of the association between non-HDL and T2D were not affected by region, proportion of men, sample size, or adjustment for confounders (including BMI, hypertension, waist circumference, and family history of diabetes). Higher non-HDL may be associated with an increased risk of T2D. Large prospective cohort studies are needed to validate these findings, and further studies are required in order to elucidate the underlying pathophysiologic mechanisms underlying the association between non-HDL and T2D.

Abstract Hypertension combined with hyperhomocysteinemia significantly raises the risk of ischemic stroke. Our study aimed to develop and validate a biomarker-based prediction model for ischemic stroke in Hyperhomocysteinemia-type (H-type) hypertension patients. We retrospectively included 3,305 patients in the development cohort, and externally validated in 103 patients from another cohort. Logistic regression, least absolute shrinkage and selection operator regression, and best subset selection analysis were used to assess the contribution of variables to ischemic stroke, and models were derived using four machine learning algorithms. Area Under Curve (AUC), calibration plot and decision-curve analysis respectively evaluated the discrimination and calibration of four models, then external validation and visualization of the best-performing model. There were 1,415 and 42 patients with ischemic stroke in the development and validation cohorts. The final model included 8 predictors: age, antihypertensive therapy, biomarkers (serum magnesium, serum potassium, proteinuria and hypersensitive C-reactive protein), and comorbidities (atrial fibrillation and hyperlipidemia). The optimal model, named A2BC ischemic stroke model, showed good discrimination and calibration ability for ischemic stroke with AUC of 0.91 and 0.87 in the internal and external validation cohorts. The A2BC ischemic stroke model had satisfactory predictive performances to assist clinicians in accurately identifying the risk of ischemic stroke for patients with H-type hypertension.

Abstract Background Staphylococcus aureus, a known contributor to non-healing wounds, releases vesicles (SAVs) that influence the delicate balance of host-pathogen interactions. Efferocytosis, a process by which macrophages clear apoptotic cells, plays a key role in successful wound healing. However, the precise impact of SAVs on wound repair and efferocytosis remains unknown. Methods Filtration, ultracentrifugation, and iodixanol density gradient centrifugation were used to purify the bacterial vesicles. Transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot (WB) were used to characterize the vesicles. Macrophage efferocytosis efficiency was assessed using flow cytometry and confocal microscopy, while efferocytosis at wound sites was analyzed through WB, FACS, and TUNEL staining. Hematoxylin and eosin (H&E) staining and wound size measurements were used to evaluate the wound healing process. Phosphorylation of signaling pathways was detected by WB, and efferocytosis receptor expression was measured using RNA sequencing, qPCR, and flow cytometry. siRNA and pathway inhibitors were used to investigate the roles of key receptors and signaling pathways in efferocytosis. Results We identified SAVs at infected wound sites, linking them to delayed healing of wounds. SAVs inhibit efferocytosis by activating the TLR2-MyD88-p38 MAPK signaling pathway, which regulates efferocytosis receptor genes. This activation promoted cleavage and shedding of MerTK, a crucial receptor for macrophage-driven efferocytosis. Notably, selective inhibition of p38 MAPK prevented MerTK shedding, restored efferocytosis and accelerated wound healing significantly, offering a promising therapeutic approach for chronic, non-healing wounds. Conclusion These findings uncover a novel mechanism in S. aureus-infected wounds, highlighting how the disruption of efferocytosis via the TLR2-MyD88-p38 MAPK-MerTK axis becomes a key force behind impaired healing of wounds. Targeting this pathway could open up a new therapeutic avenue facilitating the treatment of chronic, non-healing skin injuries.

Abstract Post-transplant diabetes mellitus (PTDM) is a common complication following renal transplantation, and its incidence has been gradually increasing in recent years, posing a significant public health challenge. Managing PTDM is complex, as studies suggest that it involves changes in the microbial flora across multiple organs. Recent research highlights the critical role of gut flora metabolism in the development of diabetes among post-renal transplant patients. This paper reviews the alterations in gut flora observed in PTDM patients and explores how gut flora influences PTDM. These findings may offer new perspectives on targeting gut flora metabolites for the prevention and treatment of PTDM.

Promoting the precipitation of Guinier-Preston (G.P.) zones in fast-extruded Mg-Al-Ca-Mn alloys could enhance the age-hardenability, which remains a significant challenge. Herein, we report an unexpected enhancement of age-hardenability in a Mg-0.35Al-0.13Ca-0.18Mn alloy (at.%) by a mere addition of 0.02 at.% Ag, i.e. the hardening response increases from 38 MPa to 59 MPa. The Ag addition is demonstrated to promote the early-stage solute clustering, which is responsible for the promoted precipitation of G.P. zones with a denser distribution. Our findings may provide new insights into the development of fast-extruded Mg-Al-Ca-Mn alloys with high strength.

The preparation of large-scale magnesium (Mg) alloy parts by wire arc additive manufacturing (WAAM) has broad application prospects, including automotive and aerospace industries. The chemical composition of Mg alloy wires plays a critical role in determining mechanical properties of WAAM Mg alloys. However, types of Mg alloy wires for WAAM need to be extended, in order to improve mechanical properties. Therefore, in the present work, a novel ATZM31 Mg alloy wire has been prepared and applied to the cold metal transfer (CMT)-WAAM process. This study focuses on understanding the forming quality, microstructure evolution, and mechanical properties of the ATZM31 alloy thin-wall component fabricated by WAAM. The results show that the Mg alloy thin-wall component possesses satisfactory formability, with minor sidewall roughness. The ATZM31 thin-wall component is mainly composed of columnar dendrites and equiaxed dendrites of the α-Mg phase, with the η-Al8Mn5 phase distributes dispersedly at grain boundaries. The area fraction of the η-Al8Mn5 phase is estimated to be ∼0.21% based on the statistical analysis of SEM images. Due to different cooling behaviors, the distribution of grain size along the build direction of the thin-walled component is uneven. The average grain size is ∼46 µm, ∼74 µm and ∼61 µm at the bottom, middle and top of the ATZM31 alloy thin-wall component, respectively. From the substrate to the top of the ATZM31 alloy thin-wall component, the hardness decreases gradually. The ultimate tensile strength along the deposition direction and build direction are ∼225 MPa and ∼214 MPa, respectively, without pronounced anisotropy. The ATZM31 alloy thin-wall component fabricated by WAAM exhibits a comparable ultimate tensile strength to forged AZ31 Mg alloys and weaker anisotropy than wrought Mg alloys.

Abstract Background polyunsaturated fatty acids (PUFAs) are a category of fatty acids that contain omega-3 and omega-6 fatty acids, which constitute a substantial portion of the Western diet and are vital for maintaining human wellness. The extent to which circulating PUFAs influence the effects of BMI on leukocyte telomere length (LTL) is unknown. Additionally, the impact of circulating PUFA on LTL remains controversial in observational studies. Methods Using publicly accessible datasets, a genome-wide association study (GWAS) was carried out to determine genetic association estimates for BMI, circulating PUFAs, and LTL. The circulating PUFAs considered were omega-3 PUFAs (i.e., docosahexaenoic acid (DHA) and total omega-3 PUFAs) and omega-6 PUFAs (i.e., linoleic acid (LA) and total omega-6 PUFAs). Two-sample Mendelian randomization (MR) was used to investigate the causal relationships between BMI and PUFA with LTL. Additionally, we examined whether certain PUFA mediate the impact of BMI on LTL. Results None of the evidence supported a causal effect of genetically predicted DHA and total omega-3 PUFA on LTL (DHA: β = 0.001, 95% CI: −0.023 to 0.026, p = 0.926; total omega-3 PUFA: β = 0.008, 95% CI: −0.013 to 0.029, p = 0.466). After conducting sensitivity analyses to account for various models of horizontal pleiotropy, the causal association between higher levels of LA and longer LTL persisted (β = 0.034, 95% CI 0.016 to 0.052, p

Abstract: Dental data can reveal evidence for a past population's oral health, nutrition, and certain cultural activities. This study aims to explore oral health and dental attrition during the late Bronze Age in order to explore health outcomes in different subgroups as well as aspects of foodways and changes in subsistence strategies during the second millennium BCE in northwest China. To do this, the skeletal remains of adult individuals associated with the Siwa material culture (1400–1100 BC) from the Mogou site (n = 28) were macroscopically assessed and compared with previously published data derived from a subsample of individuals associated with Qijia period material culture complex (1750–1400 BC) from the same site. The results show that the Siwa‐period population experienced a high frequency of carious lesions and antemortem tooth loss associated with advanced attrition (of both molars and nonmolar teeth), which did not vary significantly by sex. Females had a higher prevalence of carious lesions and antemortem tooth loss than did males, while males had a higher prevalence of dental calculus. These male/female health outcomes are also attested during the earlier Qijia period at the Mogou site. The Siwa period differs from the Qijia in that females experienced slightly worse attrition than their predecessors. Overall, oral health does not diverge significantly between the Qijia and Siwa periods, suggesting that the factors that contributed to oral health including dietary practices may have persisted diachronically for individuals buried at this site.

Abstract Sleepiness is commonly associated with neuroinflammation; however, the underlying neuroregulatory mechanisms remain unclear. Previous research suggests that the paraventricular thalamus (PVT) plays a crucial role in regulating sleep‐wake dynamics; thus, neurological abnormalities in the PVT may contribute to neuroinflammation-induced sleepiness. To test this hypothesis, we performed electroencephalography recordings in mice treated with lipopolysaccharide (LPS) and found that the mice exhibited temporary sleepiness lasting for 7 days. Using the Fos-TRAP method, fiber photometry recordings, and immunofluorescence staining, we detected temporary PVT neuron hypoactivation and microglia activation from day 1 to day 7 post-LPS treatment. Combining the results of bulk and single-cell RNA sequencing, we found upregulation of aconitate decarboxylase 1 (Acod1) in PVT microglia post-LPS treatment. To investigate the role of Acod1, we manipulated Acod1 gene expression in PVT microglia via stereotactic injection of short hairpin RNA adenovirus. Knockdown of Acod1 exacerbated inflammation, neuronal hypoactivation, and sleepiness. Itaconate is a metabolite synthesized by the enzyme encoded by Acod1. Finally, we confirmed that exogenous administration of an itaconate derivative, 4-octyl itaconate, could inhibit microglia activation, alleviate neuronal dysfunction, and relieve sleepiness. Our findings highlight PVT’s role in inflammation-induced sleepiness and suggest Acod1 as a potential therapeutic target for neuroinflammation.

Achieving impressive superplasticity is an important strategy to manufacture Mg alloy products with complex shapes. In the present study, we report that an excellent superplastic deformation with elongation larger than 500% can be achieved at 623 K and 1.0 × 10−3 s−1 in a Mg-1.51Zn-0.59Ca-0.59Al-0.70Mn (wt.%, ZXAM2111) alloy fabricated by equal-channel angular pressing. The superplastic deformation is mainly carried by grain boundary sliding (GBS), accompanied by a grain size growth from ∼3.0 µm to ∼6.0 µm after deformation. Before deformation, the ZXAM2111 alloy is mainly characterized by a strong co-segregation of Zn and Ca atoms at grain boundaries and uniformly distributed β-Mn particles. With deformation proceeding, the β-Mn particles further dynamically precipitate along grain boundaries that parallel the tensile axis, leading to improved resistance to grain coarsening. Although the enhanced stabilizing effects decrease the strain rate sensitivity value, the resulting impressive microstructure stability provides a cornerstone of the active operation of GBS, facilitating the achievement of superplastic deformation. The present work could provide insight into developing low-alloyed Mg alloys with high microstructure thermal stability to achieve superplasticity.

Abstract Purpose To evaluate 18F-FDG myocardial metabolism imaging (MMI) using a total-body PET/CT scanner and explore the feasible scan duration to guide the clinical practice. Methods A retrospective analysis was conducted on 41 patients who underwent myocardial perfusion-metabolism imaging to assess myocardial viability. The patients underwent 18F-FDG MMI with a total-body PET/CT scanner using a list-mode for 600 s. PET data were trimmed and reconstructed to simulate images of 600-s, 300-s, 120-s, 60-s, and 30-s acquisition time (G600-G30). Images among different groups were subjectively evaluated using a 5-point Likert scale. Semi-quantitative evaluation was performed using standardized uptake value (SUV), myocardial to background activity ratio (M/B), signal to noise ratio (SNR), contrast to noise ratio (CNR), contrast ratio (CR), and coefficient of variation (CV). Myocardial viability analysis included indexes of Mismatch and Scar. G600 served as the reference. Results Subjective visual evaluation indicated a decline in the scores of image quality with shortening scan duration. All the G600, G300, and G120 images were clinically acceptable (score ≥ 3), and their image quality scores were 4.9 ± 0.3, 4.8 ± 0.4, and 4.5 ± 0.8, respectively (P > 0.05). Moreover, as the scan duration reduced, the semi-quantitative parameters M/B, SNR, CNR, and CR decreased, while SUV and CV increased, and significant difference was observed in G300-G30 groups when comparing to G600 group (P

Abstract Psoriasis is a chronic inflammatory skin disorder with multiple causes, including genetic and environmental factors. Despite advances in treatment, there remains a need to identify novel therapeutic targets. A Mendelian randomization (MR) analysis was conducted to identify therapeutic targets for psoriasis. Data on cis-expression quantitative trait loci were obtained from the eQTLGen Consortium (n = 31,684). Summary statistics for psoriasis (outcome) were sourced from the GWAS Catalog with a sample size of 484,598, including 5,427 cases and 479,171 controls. Colocalization analysis was used to assess whether psoriasis risk and gene expression were driven by shared single nucleotide polymorphisms. Drug prediction and molecular docking were utilized to validate the pharmacological value of the drug targets. The MR analysis found that 81 drug targets were significantly associated, and two (TYK2 and PRSS36) were supported by colocalization analysis (PP.H4 > 0.80). Phenome-wide association studies did not show any associations with other traits at the gene level. Biologically, these genes were closely related to immune function. Molecular docking revealed strong binding with drugs and proteins, as supported by available structural data. This study validated TYK2 as a drug target for psoriasis, in line with its existing clinical use, including the development of decucravacitinib. PRSS36 is a potential novel target requiring further investigation.

Abstract Tinnitus has been identified as a potential contributor to anxiety. Thalamo-cortical pathway plays a crucial role in the transmission of auditory and emotional information, but its casual link to tinnitus-associated anxiety remains unclear. In this study, we explore the neural activities in the thalamus and cortex of the sodium salicylate (NaSal)-treated mice, which exhibit both hyperacusis and anxiety-like behaviors. We find an increase in gamma band oscillations (GBO) in both auditory cortex (AC) and prefrontal cortex (PFC), as well as phase-locking between cortical GBO and thalamic neural activity. These changes are attributable to a suppression of GABAergic neuron activity in thalamic reticular nucleus (TRN), and optogenetic activation of TRN reduces NaSal-induced hyperacusis and anxiety-like behaviors. The elevation of endocannabinoid (eCB)/ cannabinoid receptor 1 (CB1R) transmission in TRN contributes to the NaSal-induced abnormalities. Our results highlight the regulative role of TRN in the auditory and limbic thalamic-cortical pathways.

Food bioactive compounds, such as polyphenols, carotenoids, functional proteins and unsaturated fatty acids, have been used as important ingredients of functional foods due to their diverse biological activities. However, the low aqueous solubility, poor stability and limited bioavailability of these compounds limit their applications in the food industry. The preparation of delivery carriers from natural food macromolecules offers a promising approach to enhance the solubility, stability, and bioavailability of bioactive compounds. As a novel delivery system, intelligent responsive delivery carriers enable precise targeted and controlled release of bioactive compounds, thus improving their bioavailability. In addition, the delivery carriers have the capacity to effectively improve the added nutritional value, enhance the sensory properties, and extend the shelf life of functional foods. This review summarizes the functional properties of food bioactive compounds, the challenges in their application and their steady-state delivery strategies, with a particular emphasis on the common intelligent responsive delivery carriers and their mechanisms of action. Finally, this article discusses the application of these delivery carriers in functional foods, and provides an outlook on future research on bioactive compound delivery systems.

Abstract Background Immunotherapy has revolutionized the treatment of ovarian cancer (OC), but different immune microenvironments often constrain the efficacy of immunotherapeutic interventions. Therefore, there is an imperative to delineate novel immune subtypes for development of efficacious immunotherapeutic strategies. Methods The immune subtypes of OC were identified by consensus cluster analysis. The differences in clinical features, genetic mutations, mRNA stemness (mRNAsi) and immune microenvironments were analyzed among subtypes. Subsequently, prognostic risk models were constructed based on differentially expressed genes (DEGs) of the immune subtypes using weighted correlation network analysis. Results OC patients were classified into three immune subtypes with distinct survival rates and clinical features. Different subtypes exhibited varying tumor mutation burdens, homologous recombination deficiencies, and mRNAsi levels. Significant differences were observed among immune subtypes in terms of immune checkpoint expression and immunogenic cell death. Prognostic risk models were validated as independent prognostic factors demonstrated great predictive performance for survival of OC patients. Conclusion In this study, three distinct immune subtypes were identified based on gene sets related to vaccine response, with the C2 subtype exhibiting significantly worse prognosis. While no statistically significant differences in tumor mutation burden (TMB) were observed across the three subtypes, the homologous recombination deficiency (HRD) score and mRNA stemness index (mRNAsi) were notably elevated in the C2 group compared to the others. Immune infiltration analysis indicated that the C2 subtype may have an increased presence of regulatory T (Treg) cells, potentially contributing to a more favorable response to combination therapies involving PARP inhibitors and immunotherapy. These findings offer a precision medicine approach for tailoring immunotherapy in ovarian cancer patients. Moreover, the C3 subtype demonstrated significantly lower expression levels of immune checkpoint genes, a pattern validated by independent datasets, and associated with a better prognosis. Further investigation revealed that the immune-related gene FCRL5 correlates with ovarian cancer prognosis, with in vitro experiments showing that it influences the proliferation and migration of the ovarian cancer cell line SKOV3.

Abstract Ferroptosis is an important pathological mechanism of chronic heart failure (CHF). This study aimed to investigate the protective mechanism of Astragaloside IV (AS-IV) on CHF rats by integrating bioinformatics and ferroptosis. CHF-related targets and ferroptosis-related targets were collected. After the intersection, the common targets were obtained. The PPI network of the common targets was constructed, and topological analysis of the network was carried out. The target with the highest topological parameter values was selected as the key target. The key target p53 was obtained through bioinformatics analysis, and its molecular docking model with AS-IV was obtained, as well as molecular dynamics simulation analysis. The rat models of CHF after myocardial infarction were established by ligation of left coronary artery and treated with AS-IV for 4 weeks. AS-IV treatment significantly improved cardiac function in CHF rats, improved cardiomyocyte morphology and myocardial fibrosis, reduced mitochondrial damage, decreased myocardial MDA and Fe2+ content, increased GSH content, inhibited the expression of p53 and p-p53, and up-regulated the expression of SLC7A11 and GPX4. In conclusion, AS-IV improved cardiac function in CHF rats, presumably by regulating p53/SLC7A11/GPX4 signaling pathway and inhibiting myocardial ferroptosis.

Abstract Multiple synchronous lung cancers (MSLCs) constitute a unique subtype of lung cancer. To explore the genomic and immune heterogeneity across different pathological stages of MSLCs, we analyse 16 MSLCs from 8 patients using single-cell RNA-seq, single-cell TCR sequencing, and bulk whole-exome sequencing. Our investigation indicates clonally independent tumours with convergent evolution driven by shared driver mutations. However, tumours from the same individual exhibit few shared mutations, indicating independent origins. During the transition from pre-invasive to invasive adenocarcinoma, we observe a shift in T cell phenotypes characterized by increased Treg cells and exhausted CD8+ T cells, accompanied by diminished cytotoxicity. Additionally, invasive adenocarcinomas exhibit greater neoantigen abundance and a more diverse TCR repertoire, indicating heightened heterogeneity. In summary, despite having a common genetic background and environmental exposure, our study emphasizes the individuality of MSLCs at different stages, highlighting their unique genomic and immune characteristics.

Abstract Objective To explore the distribution of thrombin–antithrombin complex (TAT), plasmin-α2-antiplasmin inhibitor complex (PIC), thrombomodulin (TM), and tissue plasminogen activator-inhibitor complex (t-PAIC) in healthy older Chinese adults, and establish the reference intervals (RIs). Methods The Biotech Shine i2900 chemiluminescence immune assay was used to measure the plasma concentrations of TAT, PIC, TM, and t-PAIC in 1628 adults ≥ 60 years. The RIs were established using the 2.5th and 97.5th percentiles of the distribution. Results TAT levels were lower in males than females across all ages. Differences between the ages of 60–79 and ≥ 80 in both sex groups were statistically significant, with an upward trend with age. PIC levels showed no difference between the sexes but increased with age in both groups. TM levels did not differ between the sex groups, with slight fluctuation with age. The level in females aged 60–69 was slightly higher than that in the other groups; the difference was statistically significant. T-PAIC levels were not significantly different between the sex groups, with less fluctuation with sex and age. The level in males ≥ 80 years old was slightly lower than that in the other groups; the difference was statistically significant. The RIs for all markers in healthy older Chinese adults were determined and statistically reported by age and sex. For TAT, the RIs for males aged 60–79 and ≥ 80 are 0.51–2.30 ng/mL and 0.88–3.72 ng/mL, respectively, whereas for females aged 60–79 and ≥ 80, the RIs are 0.68–2.82 ng/mL and 1.02–3.67 ng/mL, respectively. For PIC, the RIs for the age groups 60–69, 70–79, and ≥ 80 are 0.10–0.89 µg/mL, 0.12–1.00 µg/mL, and 0.21–1.04 µg/mL, respectively. The RI of TM for females aged 60–69 is 3.32–13.22 TU/mL, whereas it is 2.96–13.26 TU/mL for the other groups. The RI of t-PAIC for males aged ≥ 80 is 1.63–10.68 ng/mL, whereas it is 2.33–11.34 ng/mL for the other groups. Conclusions Discrepancies exist in thrombus markers among different sex and age groups. The RIs of TAT, PIC, TM and t-PAIC for healthy older Chinese adults were successfully established.

ABSTRACT It is well known that gut microbial imbalance is a potential factor for the occurrence and development of diabetes mellitus (DM) and its complications. Moreover, the heart and gut microbiota can regulate each other through the gut–metabolite–heart axis. In this study, metagenomics, metabolomics, and transcriptomics were chosen to sequence the changes in gut microbiota, serum metabolite levels, and differentially expressed genes (DEGs) in leptin receptor-deficient db/db mice and analyze the correlation between serum metabolites and gut microbiota or DEGs. According to the results, there were significant differences in the 1,029 cardiac genes and 353 serum metabolites in diabetic mice of the db/db group, including DEGs enriched in the PPAR signaling pathway and increased short-chain carboxylic acids (CAs), when compared with the normal db/m group. According to metagenomics, the gut microbiota of mice in the db/db group were disrupted, and particularly Lachnospiraceae bacteria and Oscillospiraceae bacteria significantly decreased. Also, according to the Pearson correlation analysis, a significant positive correlation was found between CAs and PPAR signaling pathway-related DEGs, and a negative correlation was found between CAs and the abundance of the above-mentioned species. To sum up, type 2 diabetes mellitus (T2DM) can upregulate the expression of partial cardiac genes through the levels of serum short-chain CAs affected by gut microbiota, thus playing a role in the occurrence and development of diabetic cardiomyopathy (DCM).IMPORTANCEOur research results clearly link the changes in heart genes of T2DM and normal mice with changes in serum metabolites and gut microbiota, indicating that some genes in biological processes are closely related to the reduction of protective microbiota in the gut microbiota. This study provides a theoretical basis for investigating the mechanism of DCM and may provide preliminary evidence for the future use of gut microbiota therapy for DCM.

The intervertebral disks (IVD) serve as shock absorbers in the spine. As the largest avascular tissue in the human body, it has a limited capacity for regeneration. To address this issue, various innovative biomimetic materials have been explored to facilitate IVD regeneration at both microscopic and macroscopic levels. Techniques such as electrostatic spinning and fiber‐winding machines have been employed to prepare biomimetic materials. In this review, the physiological structure of the IVD is described, and advanced studies on its microstructure are summarized. The techniques used in biomimetic biomaterial development are further investigated, and biomimetic materials that facilitate IVD regeneration are systematically explored. Specifically, this article provides a detailed description and summary of the key features of biomimetic materials, including the types of loads they can withstand and their regenerative effects. Finally, a prospective outlook for the development and application of biomimetic materials in IVD regeneration is presented.

Background and objectiveThere is a close correlation between bone loss, depression, and antidepressants. N-3 PUFA supplementation has been considered an effective add-on therapeutic approach in ameliorating bone loss and relieving depression. However, the adjunctive effect of n-3 PUFA on bone metabolism in participants with depression is still unknown. This is a pilot study to investigate the dynamics of bone metabolism in depression and evaluate the efficacy of fish oil on bone loss in depression.MethodsIn this study, we focused on the change of bone turnover markers in depression, the effect of n-3 PUFA supplementation on bone turnover markers, and its association with clinical characteristics. A case–control study and a secondary analysis of a previously published randomized clinical trial (NCT03295708) that evaluates the efficacy of n-3 PUFA supplementation in venlafaxine-treated depressed participants have been included.ResultsThe levels of PINP (z = −2.233, p = 0.026) in depressed participants were significantly increased compared with healthy controls at baseline. The secondary analysis has shown significant differences exited on CTX (χ2 = 4.848, p = 0.028) and OSTEOC (χ2 = 6.178, p = 0.013) between n-3 PUFA and placebo group. The levels of CTX and OSTEOC (p

Largemouth bass (Micropterus salmoides) is poor at utilizing starch, and it is not clear whether commensal microorganisms can alleviate the adverse influences of high wheat starch in M. salmoides. Here, twelve autochthonous microorganisms with amylase producing abilities were isolated from the M. salmoides fed with diets containing 6 %, 12 %, or 18 % starch. Among them, Citrobacter freundii F1, Bacillus altitudinis F7, Enterococcus casseliflavus D12, Plesiomonas shigelloides D15, Bacillus cabrialesii D16, Citrobacter portucalensis K25 and Serratia oryzae K28 showed no hemolytic activity and were safety for M. salmoides. A 42-d feeding experiment was performed to study the functions of the seven microorganisms. A total of 810 fish (5.9 ± 0.01 g) were equally distributed into 9 groups. The control groups C6 and C18 were respectively fed with 6 % and 18 % wheat starch diets, the groups F1, F7, D12, D15, D16, K25 and K28 were fed with 18 % wheat starch diets respectively supplemented with 1.0×108 CFU/g C. freundii F1, B. altitudinis F7, E. casseliflavus D12, P. shigelloides D15, B. cabrialesii D16, C. portucalensis K25 and S. oryzae K28. The results indicated that compared with 6 % starch, 18 % level inhibited the growth performance, increased the hepatic glycogen and fat contents, improved the activities of glycolysis-related enzymes (hexokinase (HK), glucokinase (GK), phosphofructokinase (PFK), pyruvate kinase (PK)), decreased the activities of gluconeogenesis-related enzymes, pyruvate carboxylase (PC) and phosphoenolpyruvate carboxykinase (PEPCK), promoted the activity of lipid synthases-related enzyme carnitine palmitoyl transferaseⅠ (CPT1) and reduced the activity of lipolytic enzymes-related lipoprotein lipase (LPL). C. freundii F1, P. shigelloides D15, C. portucalensis K25 and S. oryzae K28 had relatively poor alleviating effects, while B. altitudinis F7, E. casseliflavus D12 and B. cabrialesii D16 significantly promoted the final body weight (FBW), weight gain rate (WGR), specific growth rate (SGR), protein efficiency ratio (PER), decreased feed conversion rate (FCR), significantly reduced the hepatic glycogen and fat contents, decreased the activities of glycolysis-related enzymes (HK, GK, PK), improved the activities of gluconeogenesis-related enzymes (PC, PEPCK), reduced the activity of lipid synthases-related enzyme CPT1 (P < 0.05), which proved that these three strains could effectively alleviate the negative effects of high starch in M. salmoides. In conclusion, among the seven autochthonous microorganisms, B. altitudinis F7, E. casseliflavus D12 and B. cabrialesii D16 presented better potential advantages in improving glucose and lipid metabolisms, thus promoting the growth performance of M. salmoides fed with high wheat starch diet.

Abstract Objective Recent studies have indicated a potential association between giant cell arteritis (GCA) and diabetes mellitus, encompassing both type 1 diabetes (T1D) and type 2 diabetes (T2D). However, the exact nature of this relationship requires further investigation to be fully elucidated. Methods Genetic links between T1D/T2D and GCA were explored using data from genome-wide association studies available to the public, focusing on populations of European ancestry. We applied a bidirectional mendelian randomization (MR) approach to assess the potential association between these diseases. Confirmatory analyses, including additional datasets and a comprehensive meta-analysis, were utilized. The inverse-variance-weighted (IVW) method was applied to pinpoint heterogeneity and pleiotropy, while subsequent sensitivity analyses aimed to trace the origins of any heterogeneity. Results Initial analysis demonstrated a correlation between T1D and an elevated likelihood of developing GCA (IVW odds ratio = 1.33, with a 95% confidence interval of 1.22–1.46, and a P-value of 9.42E−10). The causal association was verified through four validation datasets and meta-analysis (all P-value

Abstract Observational data suggest a link between gut microbiota and immune-related vasculitis, but causality remains unclear. A bidirectional mendelian randomization study was conducted using public genome-wide data. The inverse-variance-weighted (IVW) method identified associations and addressed heterogeneity.Families Clostridiaceae 1 and Actinomycetaceae correlated positively with granulomatosis with polyangiitis risk, while classes Lentisphaeria and Melainabacteria, and families Lachnospiraceae and Streptococcaceae showed negative associations. Behçet's disease was positively associated with the risk of family Streptococcaceae abundance. And other several gut microbiota constituents were identified as potential risk factors for immune-related vasculitis. Furthermore, combining positive association results from the IVW analysis revealed numerous shared gut microbiota constituents associated with immune-related vasculitis. MR analysis demonstrated a causal association between the gut microbiota and immune-related vasculitis, offering valuable insights for subsequent mechanistic and clinical investigations into microbiota-mediated immune-related vasculitis.

Abstract Primary familial brain calcification (PFBC) is a genetic neurological disorder characterized by symmetric brain calcifications that manifest with variable neurological symptoms. This study aimed to explore the genetic basis of PFBC and elucidate the underlying pathophysiological mechanisms. Six patients from four pedigrees with brain calcification were enrolled. Whole-exome sequencing identified two novel homozygous variants, c.488G > T (p.W163L) and c.2135G > A (p.W712*), within the myogenesis regulating glycosidase (MYORG) gene. Cerebellar ataxia (n = 5) and pyramidal signs (n = 4) were predominant symptoms, with significant clinical heterogeneity noted even within the same family. An autopsy of one patient revealed extensive brainstem calcifications, sparing the cerebral cortex, and marked by calcifications predominantly in capillaries and arterioles. The pathological study suggested morphological alterations characterized by shortened foot processes within astrocytes in regions with pronounced calcification and decreased immunoreactivity of AQP4. The morphology of astrocytes in regions without calcification remains preserved. Neuronal loss and gliosis were observed in the basal ganglia, thalamus, brainstem, cerebellum, and dentate nucleus. Notably, olivary hypertrophy, a previously undescribed feature in MYORG-PFBC, was discovered. Neuroimaging showed reduced blood flow in the cerebellum, highlighting the extent of cerebellar involvement. Among perivascular cells constituting the blood-brain barrier (BBB) and neurovascular unit, MYORG is most highly expressed in astrocytes. Astrocytes are integral components of the BBB, and their dysfunction can precipitate BBB disruption, potentially leading to brain calcification and subsequent neuronal loss. This study presents two novel homozygous variants in the MYORG gene and highlights the pivotal role of astrocytes in the development of brain calcifications, providing insights into the pathophysiological mechanisms underlying PFBC associated with MYORG variants.

To study the pollution status of the five water systems of Poyang Lake, this paper analyzes and evaluates the water quality of the Ganjiang River, Xinjiang River, Fuhe River, Xiuhe River, and Raohe River by adopting the gray correlation method, the single-factor evaluation method and the comprehensive pollution index evaluation method. Five evaluation factors, namely, dissolved oxygen, potassium permanganate, ammonia nitrogen, total nitrogen, and total phosphorus are selected. The results show that the overall water quality of the studied waters is between Class I and Class III, with all five rivers showing excessive total nitrogen levels throughout the year due to agricultural wastewater discharge, and low dissolved oxygen levels in July and August due to high temperatures. By using the gray correlation method, single factor evaluation method, and integrated pollution index evaluation method, the study analyzes the advantages and disadvantages of the three methods, and compares and synthesizes the evaluation results. Specifically, the integrated pollution index method and the gray correlation method provide more objective results, and the results of the study can be used as a reference for the prevention and control of water pollution in the "Five Rivers" as well as for the integrated management of water quality.

Background: Cannabidiol (CBD), extracted from Cannabis sativa, has anticancer, anti-inflammation, and analgesic effects. Nevertheless, its therapeutic effect and the mechanism by which it alleviates oral mucositis (OM) remain unclear. Aims: To explore the impact of CBD on OM in mice and on human oral keratinocyte (HOK) cells. Study Design: Expiremental study. Methods: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, GeneCard, DisGeNET, and Gene Expression Omnibus databases were used to conduct therapeutic target gene screening for drugs against OM. Cytoscape software was used to build networks linking components, targets, and diseases. The STRING database facilitated analysis of intertarget action relationships, and the target genes were analyzed for Kyoto Encyclopedia of Genes and Genomes pathway enrichment. Occurrence of serum inflammation-related factors, hematoxylin and eosin staining, and immunohistochemistry were used to assess OM injury. Cell proliferation, migration, pyroptosis, and apoptosis of HOK cells under different treatments were assessed. Molecular mechanisms were elucidated through western blot and quantitative real-time polymerase chain reaction analyses. Results: A total of 49 overlapping genes were pinpointed as potential targets, with NF-κB1, PIK3R1, NF-κBIA, and AKT1 being recognized as hub genes among them. Additionally, the PI3K/Akt/NF-κB and interleukin-17 signaling pathways were identified as relevant. Our in vivo experiments showed that CBD significantly reduced the proportion of lesion area, mitigated oral mucosal tissue lesions, and downregulated the expression levels of genes and levels of proteins, including NLRP3, P65, AKT, and PI3K. In vitro experiments indicated that CBD enhanced HOK cell proliferation and migration and reduced apoptosis through inhibition of the PI3K/Akt/NF-κB signaling pathway and pyroptosis. Conclusion: Our findings suggest a novel mechanism for controlling OM, in which CBD suppresses the PI3K/Akt/NF-κB signaling pathway and pyroptosis, thereby mitigating OM symptoms.

Abstract Glioma is the most common malignant tumor in the central nervous system, and its unique pathogenesis often leads to poor treatment outcomes and prognosis. In 2021, the World Health Organization (WHO) divided gliomas into five categories based on their histological characteristics and molecular changes. Non-coding RNA is a type of RNA that does not encode proteins but can exert biological functions at the RNA level, and long non-coding RNA (lncRNA) is a type of non-coding RNA with a length exceeding 200 nt. It is controlled by various transcription factors and plays an indispensable role in the regulatory processes in various cells. Numerous studies have confirmed that the dysregulation of lncRNA is critical in the pathogenesis, progression, and malignancy of gliomas. Therefore, this article reviews the proliferation, apoptosis, invasion, migration, angiogenesis, immune regulation, glycolysis, stemness, and drug resistance changes caused by the dysregulation of lncRNA in gliomas, and summarizes their potential clinical significance in gliomas.

Texture regulation is a prominent method to modify the mechanical properties and anisotropy of magnesium alloy. In this work, the Mg-1Al-0.3Ca-0.5Mn-0.2Gd (wt.%) alloy sheet with TD-tilted and circular texture was fabricated by unidirectional rolling (UR) and multidirectional rolling (MR) method, respectively. Unlike generating a strong in-plane mechanical anisotropy in conventional TD-tilted texture, the novel circular texture sample possessed a weak in-plane yield anisotropy. This can be rationalized by the similar proportion of soft grains with favorable orientation for basal slip and {101¯2} tensile twinning during the uniaxial tension of circular-texture sample along different directions. Moreover, compared with the TD-tilted texture, the circular texture improved the elongation to failure both along the rolling direction (RD) and transverse direction (TD). By quasi-in-situ EBSD-assisted slip trace analysis, higher activation of basal slip was observed in the circular-texture sample during RD tension, contributing to its excellent ductility. When loading along the TD, the TD-tilted texture promoted the activation of {101¯2} tensile twins significantly, thus providing nucleation sites for cracks and deteriorating the ductility. This research may shed new insights into the development of formable and ductile Mg alloy sheets by texture modification.

In recent years, climate change and marine pollution have significantly degraded coral reefs, highlighting the urgent need for automated coral detection to monitor marine ecosystems. However, underwater coral detection presents unique challenges, including low image contrast, complex coral structures, and dense coral growth, which limit the effectiveness of general object detection algorithms. To address these challenges, we propose SCoralDet, a soft coral detection model based on the YOLO architecture. First, we introduce a Multi-Path Fusion Block (MPFB) to capture coral features across multiple scales, enhancing the model’s robustness to uneven lighting and image blurring. We further improve inference efficiency by applying reparameterization. Second, we integrate lightweight components such as GSConv and VoV-GSCSP to reduce computational overhead without sacrificing performance. Additionally, we develop an Adaptive Power Transformation label assignment strategy, which dynamically adjusts anchor alignment metrics. By incorporating soft labels and soft central region loss, our model is guided to prioritize high-quality, well-aligned predictions. We evaluate SCoralDet on the Soft-Coral dataset, achieving an inference latency of 9.52 ms and an mAP50 of 81.9. This surpasses the performance of YOLOv5 (79.9), YOLOv6 (79.4), YOLOv8 (79.5), YOLOv9 (78.3), and YOLOv10 (79.5). These results demonstrate the effectiveness and practicality of SCoralDet in underwater coral detection tasks.