Pathophysiological Relevance and Therapeutic Outlook of GPR43 in Atherosclerosis.

Atherosclerosis (AS) is an inflammatory arterial disorder that occurs due to the deposition of the excessive lipoprotein under the artery intima, mainly including low-density lipoprotein (LDL) and other apolipoprotein B-containing lipoproteins. G protein-coupled receptors (GPCRs) play a crucial role in transmitting signals in physiological and pathophysiological conditions. GPCRs recognize inflammatory mediators, thereby serving as important players during chronic inflammatory processes. It has been demonstrated that free fatty acids can function as ligands for various GPCRs, such as free fatty acid receptor (FFAR)1/GPR40, FFAR2/GPR43, FFAR3/GPR41, FFAR4/GPR120, and the lipid metabolite binding glucose-dependent insulinotropic receptor (GPR119). This review discusses GPR43 and its ligands in the pathogenesis of AS, especially focusing on its distinct role in regulating chronic vascular inflammation, inhibiting oxidative stress, ameliorating endothelial dysfunction and improving dyslipidemia. It is hoped that this review may provide guidance for further studies aimed at GPR43 as a promising target for drug development in the prevention and therapy of AS.

Phylogenetic and Chemical Probing Information as Soft Constraints in RNA Secondary Structure Prediction.

Extrinsic, experimental information can be incorporated into thermodynamics-based RNA folding algorithms in the form of pseudo-energies. Evolutionary conservation of RNA secondary structure elements is detectable in alignments of phylogenetically related sequences and provides evidence for the presence of certain base pairs that can also be converted into pseudo-energy contributions. We show that the centroid base pairs computed from a consensus folding model such as RNAalifold result in a substantial improvement of the prediction accuracy for single sequences. Evidence for specific base pairs turns out to be more informative than a position-wise profile for the conservation of the pairing status. A comparison with chemical probing data, furthermore, strongly suggests that phylogenetic base pairing data are more informative than position-specific data on (un)pairedness as obtained from chemical probing experiments. In this context we demonstrate, in addition, that the conversion of signal from probing data into pseudo-energies is possible using thermodynamic structure predictions as a reference instead of known RNA structures.

Implementation and Evaluation of Discharge Planning for Patients Undergoing Umbilical Cord Blood Transplantation.

BACKGROUND Umbilical cord blood transplantation (UCBT) patients have high rates of unplanned readmissions and poor quality of life (QoL). The aim of this study was to evaluate the effects of discharge planning on unplanned readmissions, self-efficacy, QoL, and clinical outcomes. MATERIAL AND METHODS Patients who received their first UCBT from April 2022 to March 2023 were included. Participants (n=72) were assigned to a control group (CG: received usual care) or an intervention group (IG: received discharge planning from admission to 100 days after UCBT). The cumulative readmission rates 30 days after discharge and 100 days after UCBT were analyzed using the log-rank test. Self-efficacy and QoL were assessed at admission and 100 days after UCBT using the General Self-Efficacy Scale and FACT-BMT version 4, clinical outcomes derived from medical records. RESULTS Sixty-six patients completed the study. Discharge planning did not reduce readmission rates 30 days after discharge (20.59% vs 31.25%, P=0.376) or 100 days after UCBT (29.41% vs 34.38%, P=0.629). However, the IG showed significantly better self-efficacy (P<0.001), and except for social and emotional well-being, all the other dimensions and 3 total scores of FACT-BMT in the IG were higher than for the controls at 100 days after UCBT (P<0.05). CONCLUSIONS The discharge planning program can improve self-efficacy and QoL of UCBT recipients. The implementation of discharge planning for patients undergoing UCBT was necessary for successful hospital-to-home transitions.

Genomic and Phenotypic Adaptations of Rattus tanezumi to Cold Limit Its Further Northward Expansion and Range Overlap with R. norvegicus.

Global climate change has led to shifts in the distribution ranges of many terrestrial species, promoting their migration from lower altitudes or latitudes to higher ones. Meanwhile, successful invaders have developed genetic adaptations enabling the colonization of new environments. Over the past 40 years, Rattus tanezumi (RT) has expanded into northern China (Northwest and North China) from its southern origins. We studied the cold adaptation of RT and its potential for northward expansion by comparing it with sympatric Rattus norvegicus (RN), which is well adapted to cold regions. Through population genomic analysis, we revealed that the invading RT rats have split into three distinct populations: the North, Northwest, and Tibetan populations. The first two populations exhibited high genetic diversity, while the latter population showed remarkably low genetic diversity. These rats have developed various genetic adaptations to cold, arid, hypoxic, and high-UV conditions. Cold acclimation tests revealed divergent thermoregulation between RT and RN. Specifically, RT exhibited higher brown adipose tissue activity and metabolic rates than did RN. Transcriptome analysis highlighted changes in genes regulating triglyceride catabolic processes in RT, including Apoa1 and Apoa4, which were upregulated, under selection and associated with local adaptation. In contrast, RN showed changes in carbohydrate metabolism genes. Despite the cold adaptation of RT, we observed genotypic and phenotypic constraints that may limit its ability to cope with severe low temperatures farther north. Consequently, it is less likely that RT rats will invade and overlap with RN rats in farther northern regions.

FASTKD1 as a diagnostic and prognostic biomarker for STAD: Insights into m6A modification and immune infiltration.

Fas-activated serine/threonine kinase domain 1 (FASTKD1), a known modulator of mitochondrial-mediated cell death and survival processes, has garnered attention for its potential role in various biological contexts. However, its involvement in gastric cancer remains unclear. Thus, the present study aimed to investigate the relationship between FASTKD1 expression and key factors, including clinicopathological characteristics, immune infiltration and m6A modification in stomach adenocarcinoma (STAD). The expression of FASTKD1 was analyzed in STAD and normal adjacent tissues to assess its association with clinicopathological characteristics and survival prognosis. Data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used in this study. Additionally, the findings were validated through immunohistochemical staining. Co-expression analysis of FASTKD1 was performed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (GO/KEGG) enrichment analysis, Gene Set Enrichment Analysis (GSEA) and LinkedOmics database analysis. An in-depth analysis was conducted using databases, such as Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), GEO and TCGA to explore the potential correlation between FASTKD1 expression and immune infiltration and m6A modification in STAD. The results revealed that FASTKD1 was significantly upregulated across different tumor types, including STAD. Notably, FASTKD1 was able to distinguish between tumor and normal tissue samples with accuracy. Furthermore, the expression levels of FASTKD1 were significantly associated with clinical stage and survival. Through GO/KEGG enrichment analysis and GSEA, it was revealed that the genes co-expressed with FASTKD1 were active in a variety of biological processes. Within the TIMER, GEPIA and TCGA databases, a notable inverse correlation was observed between FASTKD1 expression and the abundance of immune cell subsets. Notably, significant correlations were established between FASTKD1 and m6A modification genes, YTHDF1 and LRPPRC, in both TCGA and GEO datasets. In conclusion, FASTKD1 may serve a significant role in m6A modification and immune infiltration processes, making it a potentially valuable diagnostic and prognostic biomarker in STAD.

Implications of YWHAH Gene Expression in the Early Detection of Sepsis.

ABSTRACT: Sepsis, a complex and multifaceted condition, is a common occurrence with serious implications for critically ill patients in the Intensive Care Unit (ICU). The YWHAH gene encodes the 14-3-3n protein, a member of the 14-3-3 protein family. While existing research primarily focuses on the role of 14-3-3n in conditions such as schizophrenia and various cancers, our study revealed that the expression of the YWHAH gene remained relatively stable in both infected individuals and healthy controls. Through Venn plot analysis following weighted gene correlation network analysis (WGCNA), we observed a potential association between elevated YWHAH expression and the transition from infection to sepsis. In a comprehensive analysis of public single-cell transcriptome databases, the expression of YWHAH was found to be distinctive in cases of sepsis and infection. These findings were corroborated through an in vitro analysis utilizing real-time polymerase chain reaction. This study represents the initial identification of variations in YWHAH gene expression between patients with infection and sepsis, potentially offering insights for the development of early detection and treatment strategies for sepsis.

Effect of navigation endoscopy combined with three-dimensional printing technology in the treatment of orbital blowout fractures.

AIM: To explore the combined application of surgical navigation nasal endoscopy (NNE) and three-dimensional printing technology (3DPT) for the adjunctive treatment of orbital blowout fractures (OBF). METHODS: Retrospective analysis was conducted on the data of patients with OBF who underwent surgical treatment at the Affiliated Eye Hospital of Nanchang University between July 2012 and November 2022. The control group consisted of patients who received traditional surgical treatment (n=43), while the new surgical group (n=52) consisted of patients who received NNE with 3DPT. The difference in therapeutic effects between the two groups was evaluated by comparing the duration of the operation, best corrected visual acuity (BCVA), enophthalmos difference, recovery rate of eye movement disorder, recovery rate of diplopia, and incidence of postoperative complications. RESULTS: The study included 95 cases (95 eyes), with 63 men and 32 women. The patients' age ranged from 5 to 67y (35.21±15.75y). The new surgical group and the control group exhibited no statistically significant differences in the duration of the operation, BCVA and enophthalmos difference. The recovery rates of diplopia in the new surgical group were significantly higher than those in the control group at 1mo [OR=0.03, 95%CI (0.01-0.15), P<0.0000] and 3mo [OR=0.11, 95%CI (0.03-0.36), P<0.0000] post-operation. Additionally, the recovery rates of eye movement disorders at 1 and 3mo after surgery were OR=0.08, 95%CI (0.03-0.24), P<0.0000; and OR=0.01, 95%CI (0.00-0.18), P<0.0000. The incidence of postoperative complications was lower in the new surgical group compared to the control group [OR=4.86, 95%CI (0.95-24.78), P<0.05]. CONCLUSION: The combination of NNE and 3DPT can shorten the recovery time of diplopia and eye movement disorder in patients with OBF.

Developing Complex RNA Design Applications in the Infrared Framework.

Applications in biotechnology and bio-medical research call for effective strategies to design novel RNAs with very specific properties. Such advanced design tasks require support by computational tools but at the same time put high demands on their flexibility and expressivity to model the application-specific requirements. To address such demands, we present the computational framework Infrared. It supports developing advanced customized design tools, which generate RNA sequences with specific properties, often in a few lines of Python code. This text guides the reader in tutorial format through the development of complex design applications. Thanks to the declarative, compositional approach of Infrared, we can describe this development as a step-by-step extension of an elementary design task. Thus, we start with generating sequences that are compatible with a single RNA structure and go all the way to RNA design targeting complex positive and negative design objectives with respect to single or even multiple target structures. Finally, we present a "real-world" application of computational design to create an RNA device for biotechnology: we use Infrared to generate design candidates of an artificial "AND" riboswitch, which activates gene expression in the simultaneous presence of two different small metabolites. In these applications, we exploit that the system can generate, in an efficient (fixed-parameter tractable) way, multiple diverse designs that satisfy a number of constraints and have high quality w.r.t. to an objective (by sampling from a Boltzmann distribution).

Deletion of TECRL promotes skeletal muscle repair by up-regulating EGR2.

Myogenic regeneration relies on the proliferation and differentiation of satellite cells. TECRL (trans-2,3-enoyl-CoA reductase like) is an endoplasmic reticulum protein only expressed in cardiac and skeletal muscle. However, its role in myogenesis remains unknown. We show that TECRL expression is increased in response to injury. Satellite cell-specific deletion of TECRL enhances muscle repair by increasing the expression of EGR2 through the activation of the ERK1/2 signaling pathway, which in turn promotes the expression of PAX7. We further show that TECRL deletion led to the upregulation of the histone acetyltransferase general control nonderepressible 5, which enhances the transcription of EGR2 through acetylation. Importantly, we showed that AAV9-mediated TECRL silencing improved muscle repair in mice. These findings shed light on myogenic regeneration and muscle repair.

Artesunate induces ferroptosis by regulating MT1G and has an additive effect with doxorubicin in diffuse large B-cell lymphoma cells.

Diffuse Large B-cell lymphoma (DLBCL) is a highly aggressive disease with heterogeneous outcomes and marked variability in the response to chemotherapy. DLBCL comprises two major subtypes: germinal centre B-cell-like (GCB) and activated B-cell-like (ABC). Our study highlights the extensive antitumour activity of artesunate (ART) against both major DLBCL subtypes. Transcriptome analysis suggests the potential involvement of ferroptosis in artesunate-induced cell death. Because of low glutathione (GSH) and glutathione peroxidase 4 (GPX4) levels, along with the accumulation of free iron (Fe2+), artesunate induces the excessive production of reactive oxygen species (ROS), ultimately leading to ferroptosis, a form of cell death driven by phospholipid peroxidation. A putative target of artesunate, metallothionein 1G (MT1G), was selected for further analysis. Subsequent studies revealed that inhibiting MT1G expression in vitro significantly impedes the ferroptosis-promoting activity of artesunate by reducing lipid peroxidation and iron accumulation. We also showed that the combination of artesunate and doxorubicin had a marked additive inhibitory effect on GCB and ABC DLBCL cells. In conclusion, artesunate induces ferroptotic death in GCB and ABC DLBCL cells by attenuating the GPX4/GSH antioxidant defence system and increasing intracellular iron levels, indicating its therapeutic potential for relapsed or refractory DLBCL.

Evaluation of the mechanism of Gong Ying San activity on dairy cows mastitis by network pharmacology and metabolomics analysis.

OBJECTIVES: The goal of this investigation was to identify the main compounds and the pharmacological mechanism of the traditional Chinese medicine formulation, Gong Ying San (GYS), by infrared spectral absorption characteristics, metabolomics, network pharmacology, and molecular-docking analysis for mastitis. The antibacterial and antioxidant activities were determined in vitro. METHODS: The chemical constituents of GYS were detected by ultra-high-performance liquid chromatography Q-extractive mass spectrometry (UHPLC-QE-MS). Related compounds were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP, http://tcmspw.com/tcmsp.php) and the Encyclopedia of Traditional Chinese Medicine (ETCM, http://www.tcmip.cn/ETCM/index.php/Home/) databases; genes associated with mastitis were identified in DisGENT. A protein-protein interaction (PPI) network was generated using STRING. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment screening was conducted using the R module. Molecular-docking analyses were performed with the AutoDockTools V1.5.6. RESULTS: Fifty-four possible compounds in GYS with forty likely targets were found. The compound-target-network analysis showed that five of the ingredients, quercetin, luteolin, kaempferol, beta-sitosterol, and stigmasterol, had degree values >41.6, and the genes TNF, IL-6, IL-1ß, ICAM1, CXCL8, CRP, IFNG, TP53, IL-2, and TGFB1 were core targets in the network. Enrichment analysis revealed that pathways associated with cancer, lipids, atherosclerosis, and PI3K-Akt signaling pathways may be critical in the pharmacology network. Molecular-docking data supported the hypothesis that quercetin and luteolin interacted well with TNF-α and IL-6. CONCLUSIONS: An integrative investigation based on a bioinformatics-network topology provided new insights into the synergistic, multicomponent mechanisms of GYS's anti-inflammatory, antibacterial, and antioxidant activities. It revealed novel possibilities for developing new combination medications for reducing mastitis and its complications.

[Synthesis and tissue distribution of bufadienolides in Bufo bufo gargarizans].

This study explored the biosynthesis of bufadienolides(BDs) in Bufo bufo gargarizans to solve the dilemma of the decreasing resources of B. bufo gargarizans and provide a theoretical basis for the sustainable utilization of the resources. Ultra-high performance liquid chromatography-Orbitrap-mass spectrometry(UHPLC-Orbitrap-MS) was employed to detect the synthesis sites of BDs in B. bufo gargarizans, and the results were verified by desorption electrospray ionization-mass spectrometry imaging(DESI-MSI) and homogenate incubation experiments. BDs in B. bufo gargarizans had the highest content in the liver and the highest concentration in the gallbladder, in addition to the parotid gland and skin, which suggested that the liver could synthesize BDs. The results of DESI-MSI also showed that BDs were mainly enriched in the liver rather than the immature parotid gland. The incubation experiment of liver homogenates demonstrated the liver of B. bufo gargarizans had the ability to synthesize BDs. This study showed that the liver was a major organ for the synthesis of BDs in B. bufo gargarizans during metamorphosis, development, and growth, which provided strong theoretical support for the biosynthesis of BDs and the sustainable utilization of B. bufo gargarizans resources.

Correlation analysis of serum TLR4 protein levels and TLR4 gene polymorphisms in gouty arthritis patients.

OBJECTIVE: The Toll-like receptor (TLR) 4-mediated nuclear factor kappa B (NF-κB) signaling pathway regulates the production of inflammatory factors and plays a key role in the pathogenesis of gouty arthritis. The aim of the present study was to investigate the link among TLR4 gene polymorphisms at various loci, protein expression, and gouty arthritis susceptibility. METHODS: Between 2016 and 2021, a case-control study was used to collect a total of 1207 study subjects, including 317 male patients with gouty arthritis (gout group) and 890 healthy males (control group). The association between gout susceptibility and different genetic models was analyzed by typing three loci of the TLR4 gene (rs2149356, rs2737191, and rs10759932) using a multiplex point mutation rapid assay, and the association between protein expression and gout was confirmed by measuring TLR4 protein concentrations using enzyme-linked immunosorbent assays (ELISAs). RESULTS: In a codominant models AA and AG, the rs2737191 polymorphism in the gout group increased the risk of gout compared to the AA genotype (OR = 2.249, 95%CI 1.010~5.008), and the risk of gout was higher for those carrying the G allele compared to the A allele (OR = 2.227, 95%CI 1.006~4.932). TLR4 protein expression was different between the two groups with different locus genotypes. The differences in TLR4 protein expression between the gout group and control group were statistically significant between the following genotypes: the GG and GT genotypes of the rs2149356 polymorphism; the AA and AG genotypes of the rs2737191 polymorphism; and the TT and TC genotypes of the rs10759932 polymorphism(P<0.05). The TLR4 protein level in the gout group (19.19±3.09 ng/ml) was significantly higher than that in the control group (15.85±4.75 ng/ml). CONCLUSION: The AG genotype of the TLR4 gene rs2737191 polymorphism may be correlated with the development of gouty arthritis. The level of TLR4 protein expression is significantly higher in patients with gouty arthritis than in controls, and there is a correlation between high TLR4 protein expression and the development of gouty arthritis.

Infrared: a declarative tree decomposition-powered framework for bioinformatics.

MOTIVATION: Many bioinformatics problems can be approached as optimization or controlled sampling tasks, and solved exactly and efficiently using Dynamic Programming (DP). However, such exact methods are typically tailored towards specific settings, complex to develop, and hard to implement and adapt to problem variations. METHODS: We introduce the Infrared framework to overcome such hindrances for a large class of problems. Its underlying paradigm is tailored toward problems that can be declaratively formalized as sparse feature networks, a generalization of constraint networks. Classic Boolean constraints specify a search space, consisting of putative solutions whose evaluation is performed through a combination of features. Problems are then solved using generic cluster tree elimination algorithms over a tree decomposition of the feature network. Their overall complexities are linear on the number of variables, and only exponential in the treewidth of the feature network. For sparse feature networks, associated with low to moderate treewidths, these algorithms allow to find optimal solutions, or generate controlled samples, with practical empirical efficiency. RESULTS: Implementing these methods, the Infrared software allows Python programmers to rapidly develop exact optimization and sampling applications based on a tree decomposition-based efficient processing. Instead of directly coding specialized algorithms, problems are declaratively modeled as sets of variables over finite domains, whose dependencies are captured by constraints and functions. Such models are then automatically solved by generic DP algorithms. To illustrate the applicability of Infrared in bioinformatics and guide new users, we model and discuss variants of bioinformatics applications. We provide reimplementations and extensions of methods for RNA design, RNA sequence-structure alignment, parsimony-driven inference of ancestral traits in phylogenetic trees/networks, and design of coding sequences. Moreover, we demonstrate multidimensional Boltzmann sampling. These applications of the framework-together with our novel results-underline the practical relevance of Infrared. Remarkably, the achieved complexities are typically equivalent to the ones of specialized algorithms and implementations. AVAILABILITY: Infrared is available at https://amibio.gitlabpages.inria.fr/Infrared with extensive documentation, including various usage examples and API reference; it can be installed using Conda or from source.

Greenness, Genetic Predisposition, and Tinnitus.

This study aimed to investigate the association between residential greenness and tinnitus and the potential interaction between greenness and genetic predisposition to tinnitus. The normalized difference vegetation index (NDVI) is used to measure residential greenness. The tinnitus is defined based on self-reported. In the cross-sectional analyses, logistic regression models are used for the baseline sample of the United Kingdom Biobank cohort. In the secondary analysis, a Cox proportional hazard model is used for a subsample of participants who completed the tinnitus questionnaire at follow-up. In the cross-sectional analysis including 106471 participants, higher residential greenness is associated with lower odds of tinnitus for each interquartile range increase in continuous NDVI, with an adjusted odds ratio of 0.97 (95% confidence interval: 0.95 to 0.99) for tinnitus. A similar association is observed in the longitudinal analysis, with an adjusted hazard ratio of 0.92 (95% confidence interval: 0.86 to 0.98) for the association of NDVI increased per interquartile range with incident tinnitus. Moreover, there is a significant interaction between greenness and genetic predisposition to tinnitus (P < 0.05). This study suggested that residential greenness is negatively associated with tinnitus. Greenness and genetic predisposition to tinnitus are found to have a significant interaction.

The J bs-5YP peptide can alleviate dementia in senile mice by restoring the transcription of Slc40a1 to secrete the excessive iron from brain.

INTRODUCTION: With age and ATP decrease in the body, the transcription factors hypophosphorylation weakens the transcription of Slc40a1 and hinders the expression of the iron discharger ferroportin. This may lead to iron accumulation in the brain and the catalysis of free radicals that damage cerebral neurons and eventually lead to Alzheimer's disease (AD). OBJECTIVES: To prevent AD caused by brain iron excretion disorders and reveal the mechanism of J bs-5YP peptide restoring ferroportin. METHODS: We prepared J bs-YP peptide and administered it to the senile mice with dementia. Then, the intelligence of the mice was tested using a Morris Water Maze. The ATP content in the body was detected using the ATP hydrophysis and Phosphate precipitation method. The activation of Slc40a1 transcription was assayed with ATAC seq and the ferroportin, as well as the phosphorylation levels of Ets1 in brain were detected by Western Blot. RESULTS: The phosphorylation level of Ets1in brain was enhanced, and subsequently, the transcription of Slc40a1 was activated and ferroportin was increased in the brain, the levels of iron and free radicals were reduced, with the neurons protection, and the dementia was ultimately alleviated in the senile mice. CONCLUSION: J bs-5YP can recover the expression of ferroportin to excrete excessive iron in the brain of senile mice with dementia by enhancing the transcription of Slc40a1 via phosphorylating Ets1, revealing the potential of J bs-5YP as a drug to alleviate senile dementia.

Kazakh adults in Xinjiang have a prevalent obesity problem but a low prevalence of diabetes.

BACKGROUND: The prevalence of diabetes and obesity has been continuously rising worldwide over the last three decades, particularly in China. The prevalence varies widely among different ethnicities. In this study, we investigated the prevalence of diabetes and obesity, as well as the associated factors for diabetes in Kazakh adults in Xinjiang to improve diabetes screening. METHODS: We collected data from the Xinjiang physical examination in 2018, including a total sample of 118,505 Kazakh adults in Altay District. Data on demographic characteristics, medical history, physical examination, fasting plasma glucose (FPG) and serum lipid profiles were collected. The chi-square test was used to examine the differences between multiple variables. Multivariate logistic regression was performed to identify the factors associated with diabetes. RESULTS: The mean age was 43. 66 years (SD 14.14). 49.3% of the population were women and 75.5% were rural residents. The mean FPG was 5.33 mmol/L (SD 1.22). The prevalence of diabetes was 6.3% and 4.1% received a new diagnosis by FPG. 26.6% were diagnosed with impaired fasting glucose (IFG). The mean body mass index (BMI) was 26.29 kg/m2 (SD 14.14) and the mean waist circumference was 87.69 cm (SD 12.74). 33.2% of the population were overweight, and 33.0% were obese. The prevalence of central obesity was 51.4%. Diabetes was mostly positively associated with hypertension (OR = 3.821, P<0.001), hypertriglyceridemia (OR = 2.757, P<0.001), and hyper-LDL-cholesterolemia (OR = 2.331, P<0.001) in the Kazakh population. The ORs for overweight, obesity and central obesity predictive of diabetes were 1.265, 1.453 and 1.222 ( all P<0.001), respectively. CONCLUSIONS: Despite having a high prevalence of obesity and central obesity, the Kazakh population had a considerably low prevalence of diabetes. Obesity was not the most important risk factor for diabetes in Kazakh individuals. The awareness of diabetes was low. When screening for diabetes in Kazakhs, those with hypertension or dyslipidemia should receive more attention.

Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Ameliorate Aging-Induced BTB Impairment in Porcine Testes by Activating Autophagy and Inhibiting ROS/NLRP3 Inflammasomes via the AMPK/mTOR Signaling Pathway.

As a pivotal player in spermatogenesis, the blood-testis barrier (BTB) made from junction apparatus coexisting in Sertoli cells (SCs) is impaired with an increase in age and ultimately induces spermatogenic dysfunction or even infertility. It has been corroborated that bone marrow mesenchymal stem cell (BMSC) transplantation can efficiently repair and regenerate the testicular function. As vital mediators of cell-to-cell communication, MSC-derived exosomes (Exos) can directly serve as therapeutic agents for tissue repair and regeneration. However, the therapeutic value of BMSC-Exos in aging-induced BTB damage remains to be confirmed. In this study, we explored that the old porcine testes had defective autophagy, which aggravated BTB disruption in SCs. BMSC-Exos could decrease ROS production and NLRP3 inflammasome activation but enhanced autophagy and tight junction (TJ) function in D-gal-triggered aging porcine SCs and mouse model testes, according to in vitro and in vivo experiments. Furthermore, rapamycin, NAC, MCC950, and IL-1Ra restored the TJ function in D-gal-stimulated aging porcine SCs, while BMSC-Exos' stimulatory effect on TJ function was inhibited by chloroquine. Moreover, the treatment with BMSC-Exos enhanced autophagy in D-gal-induced aging porcine SCs by means of the AMPK/mTOR signal transduction pathway. These findings uncovered through the present study that BMSC-Exos can enhance the BTB function in aging testes by improving autophagy via the AMPK/mTOR signaling pathway, thereby suppressing ROS production and NLRP3 inflammasome activation.

Cu+-doped lead-free double perovskite quantum dots for enhancing the photovoltaic performance of carbon-based Cs2AgInCl6 perovskite solar cells.

Lead-free double perovskite solar cells (PSCs) have received widespread attention because of their non-toxic nature and three-dimensional structure. However, their photovoltaic efficiency is limited by their large bandgap, including indirect or direct forbidden. Herein, Cu+ ions are incorporated into Cs2AgInCl6 double perovskite quantum dots, following which the bandgap is effectively decreased from 3.6 to 2.9 eV. Meanwhile, a facile method of drop-coating is employed to fabricate Cs2AgInCl6 films and carbon electrodes. A carbon electrode derived from a by-product of the cane sugar industry (molasses) is used to replace the expensive hole-transport materials and metal electrodes. A 0.5% Cu+-doped Cs2AgInCl6, device fabricated using carbon-based PSCs with a stacked-architecture achieves a power conversion efficiency of 1.77%, which is 2.9 times higher than that of the original device, and displays a better stability compared with that of the control one. This study provides guidance for preparing PSCs using a low-cost, facile strategy.

SFXN1 as a potential diagnostic and prognostic biomarker of LUAD is associated with 18F-FDG metabolic parameters.

BACKGROUND: Sideroflexin 1 (SFXN1) has been discovered as a novel tumor marker for lung adenocarcinoma, but data on its importance in the development of lung adenocarcinoma is still limited. This study evaluated the correlation between SFXN1 and parameters related to 18F-flurodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT), and further explored the role of SFXN1 in the value-added and glycolytic processes of LUAD. METHOD: The expression and prognostic value of SFXN1 mRNA in LUAD were analyzed using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data base. Retrospective analysis of 18F-FDG PET imaging and metabolic parameters in 42 patients to explore the relationship between the expression of SFXN1 and glucose metabolism levels in lung adenocarcinoma and its clinical significance. H1975 cells were selected as the in vitro research object, and the biological effects of SFXN1 on LUAD were further elucidated through Edu proliferation assay, CCK8 activity assay, wound healing experiment, and cell flow cytometry. RESULT: SFXN1 is highly expressed in various tumors, including LUAD, and its high expression can serve as an independent predictor of overall survival in lung adenocarcinoma. In addition, the expression of SFXN1 in LUAD was significantly correlated with 18F-FDG PET/CT parameters: maximum and average standardized uptake values (SUVmax and SUVmean), as well as total lesion glycolysis (TLG) (rho = 0.574, 0.589, and 0.338, p < 0.05), which can predict the expression of SFXN1 with an accuracy of 0.934. In vitro functional experiments have shown that knocking down SFXN1 inhibits the proliferation and migration of LUAD cells, promotes cell apoptosis, and may inhibit tumor activity by regulating the expression of glycolytic related genes SLC2A1, HK2, GPI, ALDOA, GAPDH, ENO1, PKM, and LDHA. CONCLUSION: The overexpression of SFXN1 is closely related to FDG uptake, and SFXN1, as a promising prognostic biomarker, may mediate the development of LUAD through the glycolytic pathway.