Body mass index in patients with Parkinson's disease: a systematic review.

Body mass index (BMI) has been found to have an impact on neurodegenerative diseases such as Parkinson's disease (PD). Several studies suggested that patients with PD have a lower BMI compared with controls. However, some studies indicated the differences between patients and controls as statistically insignificant. We performed this meta-analysis to clarify the relationship between BMI and PD based on the studies published from 1975 to April 2023 in the PubMed, Embase, and Cochrane Library databases. In total, 18 case-control studies met the inclusion criteria for meta-analysis. We found a statistically significant difference in mean BMI between patients with PD and healthy controls {standardized mean difference (SMD) [95% confidence interval (CI)] = -0.36 (-0.43, -0.29), P < 0.05}. Regarding sex, seven studies were included in the meta-analysis for female/male patients with PD. The mean BMI was significantly different between males with PD and healthy males [SMD (95% CI) = -0.34 (-0.47, -0.22), P < 0.05]. Moreover, the mean BMI of females with PD was significantly different from that of corresponding healthy females [SMD (95% CI) = -0.44 (-0.57, -0.30), P < 0.05]. The meta-analysis demonstrates a significantly lower BMI in patients with PD, but no gender differences, when compared with their respective healthy individuals.NEW & NOTEWORTHY The meta-analysis demonstrates a significantly lower body mass index in patients with PD, but no gender differences, when compared with their respective healthy individuals.

Alpha-synuclein affects certain iron transporters of BV2 microglia cell through its ferric reductase activity.

Alpha-synuclein (α-syn) is a major component of Lewy bodies, which is a biomarker of Parkinson's disease (PD). It accumulates in substantia nigra pars compacta (SNpc) to form insoluble aggregates and cause neurotoxicity, which is often accompanied by iron deposition. We compared the iron reductase activity between monomeric α-syn (M-α-syn) and oligomeric α-syn (O-α-syn) and investigated the effect of α-syn on iron metabolism of BV2 microglia cells as well. α-syn had ferric reductase activity, and O-α-syn had stronger enzyme activity than M-α-syn. M-α-syn upregulated iron uptake protein, divalent metal transporter1 (DMT1) expression, and iron influx but did not regulate iron release protein ferroportin1 (FPN1) expression and iron efflux. O-α-syn elevated the expression of both DMT1 and FPN1 and thus increased the iron influx and efflux in BV2 microglial cells, but the expressions of iron regulatory protein1 (IRP1) and hypoxia-inducible factor 2α (HIF-2α) had no significant change. Moreover, both M-α-syn and O-α-syn could increase the mRNA expressions of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in BV2 microglia cells. Both types of α-syn can activate microglia, which leads to increased expressions of proinflammatory factors. α-syn can affect DMT1 and FPN1 expressions in BV2 microglia cells, which might be through its ferric reductase activity.NEW & NOTEWORTHY The effects of monomeric α-syn (M-α-syn) and oligomeric α-syn (O-α-syn) on the iron metabolism of BV2 microglia cells were detected by exogenous α-syn treatment. This study provides a strong experimental basis for α-syn involvement in iron metabolism in microglia.

Activating the healing process: three-dimensional culture of stem cells in Matrigel for tissue repair.

BACKGROUND: To establish a strategy for stem cell-related tissue regeneration therapy, human gingival mesenchymal stem cells (hGMSCs) were loaded with three-dimensional (3D) bioengineered Matrigel matrix scaffolds in high-cell density microtissues to promote local tissue restoration. METHODS: The biological performance and stemness of hGMSCs under 3D culture conditions were investigated by viability and multidirectional differentiation analyses. A Sprague‒Dawley (SD) rat full-thickness buccal mucosa wound model was established, and hGMSCs/Matrigel were injected into the submucosa of the wound. Autologous stem cell proliferation and wound repair in local tissue were assessed by histomorphometry and immunohistochemical staining. RESULTS: Three-dimensional suspension culture can provide a more natural environment for extensions and contacts between hGMSCs, and the viability and adipogenic differentiation capacity of hGMSCs were significantly enhanced. An animal study showed that hGMSCs/Matrigel significantly accelerated soft tissue repair by promoting autologous stem cell proliferation and enhancing the generation of collagen fibers in local tissue. CONCLUSION: Three-dimensional cell culture with hydrogel scaffolds, such as Matrigel, can effectively improve the biological function and maintain the stemness of stem cells. The therapeutic efficacy of hGMSCs/Matrigel was confirmed, as these cells could effectively stimulate soft tissue repair to promote the healing process by activating the host microenvironment and autologous stem cells.

Neurons upregulate PD-L1 via IFN/STAT1/IRF1 to alleviate damage by CD8+ T cells in cerebral malaria.

BACKGROUND: Cerebral malaria (CM) is the most lethal complication of malaria, and survivors usually endure neurological sequelae. Notably, the cytotoxic effect of infiltrating Plasmodium-activated CD8+ T cells on cerebral microvasculature endothelial cells is a prominent feature of the experimental CM (ECM) model with blood-brain barrier disruption. However, the damage effect of CD8+ T cells infiltrating the brain parenchyma on neurons remains unclear. Based on the immunosuppressive effect of the PD-1/PD-L1 pathway on T cells, our previous study demonstrated that the systemic upregulation of PD-L1 to inhibit CD8+ T cell function could effectively alleviate the symptoms of ECM mice. However, it has not been reported whether neurons can suppress the pathogenic effect of CD8+ T cells through the PD-1/PD-L1 negative immunomodulatory pathway. As the important inflammatory factor of CM, interferons can induce the expression of PD-L1 via different molecular mechanisms according to the neuro-immune microenvironment. Therefore, this study aimed to investigate the direct interaction between CD8+ T cells and neurons, as well as the mechanism of neurons to alleviate the pathogenic effect of CD8+ T cells through up-regulating PD-L1 induced by IFNs. METHODS: Using the ECM model of C57BL/6J mice infected with Plasmodium berghei ANKA (PbA), morphological observations were conducted in vivo by electron microscope and IF staining. The interaction between the ECM CD8+ T cells (immune magnetic bead sorting from spleen of ECM mice) and primary cultured cortical neurons in vitro was observed by IF staining and time-lapse photography. RNA-seq was performed to analyze the signaling pathway of PD-L1 upregulation in neurons induced by IFNß or IFNγ, and verified through q-PCR, WB, IF staining, and flow cytometry both in vitro and in vivo using IFNAR or IFNGR gene knockout mice. The protective effect of adenovirus-mediated PD-L1 IgGFc fusion protein expression was verified in ECM mice with brain stereotaxic injection in vivo and in primary cultured neurons via viral infection in vitro. RESULTS: In vivo, ECM mice showed infiltration of activated CD8+ T cells and neuronal injury in the brain parenchyma. In vitro, ECM CD8+ T cells were in direct contact with neurons and induced axonal damage, as an active behavior. The PD-L1 protein level was elevated in neurons of ECM mice and in primary cultured neurons induced by IFNß, IFNγ, or ECM CD8+ T cells in vitro. Furthermore, the IFNß or IFNγ induced neuronal expression of PD-L1 was mediated by increasing STAT1/IRF1 pathway via IFN receptors. The increase of PD-L1 expression in neurons during PbA infection was weakened after deleting the IFNAR or IFNGR. Increased PD-L1 expression by adenovirus partially protected neurons from CD8+ T cell-mediated damage both in vitro and in vivo. CONCLUSION: Our study demonstrates that both type I and type II IFNs can induce neurons to upregulate PD-L1 via the STAT1/IRF1 pathway mediated by IFN receptors to protect against activated CD8+ T cell-mediated damage, providing a targeted pathway to alleviate neuroinflammation during ECM.

Fine-mapping of LrN3B on wheat chromosome arm 3BS, one of the two complementary genes for adult-plant leaf rust resistance.

The common wheat line 4N0461 showed adult-plant resistance to leaf rust. 4N0461 was crossed with susceptible cultivars Nongda4503 and Shi4185 to map the causal resistance gene(s). Segregation of leaf rust response in F2 populations from both crosses was 9 resistant:7 susceptible, indicative of two complementary dominant resistance genes. The genes were located on chromosome arms 3BS and 4BL and temporarily named LrN3B and LrN4B, respectively. Subpopulations from 4N0461 × Nongda4503 with LrN3B segregating as a single allele were used to fine-map LrN3B locus. LrN3B was delineated in a genetic interval of 0.07 cM, corresponding to 106 kb based on the Chinese Spring reference genome (IWGSC RefSeq v1.1). Four genes were annotated in this region, among which TraesCS3B02G014800 and TraesCS3B02G014900 differed between resistant and susceptible genotypes, and both were required for LrN3B resistance in virus-induced gene silencing experiments. Diagnostic markers developed for checking the polymorphism of each candidate gene, can be used for marker-assisted selection in wheat breeding programs.

The function and therapeutic potential of transfer RNA-derived small RNAs in cardiovascular diseases: A review.

Transfer RNA-derived small RNAs (tsRNAs) are a class of small non-coding RNA (sncRNA) molecules derived from tRNA, including tRNA derived fragments (tRFs) and tRNA halfs (tiRNAs). tsRNAs can affect cell functions by participating in gene expression regulation, translation regulation, intercellular signal transduction, and immune response. They have been shown to play an important role in various human diseases, including cardiovascular diseases (CVDs). Targeted regulation of tsRNAs expression can affect the progression of CVDs. The tsRNAs induced by pathological conditions can be detected when released into the extracellular, giving them enormous potential as disease biomarkers. Here, we review the biogenesis, degradation process and related functional mechanisms of tsRNAs, and discuss the research progress and application prospects of tsRNAs in different CVDs, to provide a new perspective on the treatment of CVDs.

Ligand-Induced Divergent Evolution of ZnSe Magic Sized Clusters.

Alkylamine ligand-induced evolutions of ZnSe magic sized clusters (MSCs) toward divergent products have been discovered for the first time. With correspondingly assigned molecular structures, the same ZnSe MSC was found to undergo either single-atom growth or dissolution through the elaborate tailoring of alkylamine ligands.

Cytogenetic and Genomic Characterization of a Novel Wheat-Tetraploid Thinopyrum elongatum 1BS⋠1EL Translocation Line with Stripe Rust Resistance.

Stripe rust, caused by Puccinia striiformis f. sp. tritici, is a destructive wheat disease pathogen. Thinopyrum elongatum is a valuable germplasm including diploid, tetraploid, and decaploid with plenty of biotic and abiotic resistance. In a previous study, we generated a stripe rust-resistant wheat-tetraploid Th. elongatum 1E/1D substitution line, K17-841-1. To further apply the wild germplasm for wheat breeding, we selected and obtained a new homozygous wheat-tetraploid Th. elongatum translocation line, T1BS⋅1EL, using genomic in situ hybridization, fluorescence in situ hybridization (FISH), oligo-FISH painting, and the wheat 55K single nucleotide polymorphism genotyping array. The T1BS⋅1EL is highly resistant to stripe rust at the seedling and adult stages. Pedigree and molecular marker analyses revealed that the resistance gene was located on the chromosome arm 1EL of tetraploid Th. elongatum, tentatively named Yr1EL. In addition, we developed and validated 32 simple sequence repeat markers and two kompetitive allele-specific PCR assays that were specific to the tetraploid Th. elongatum chromosome arm 1EL to facilitate marker-assisted selection for alien 1EL stripe rust resistance breeding. This will help us explore and locate the stripe rust resistance gene mapping on the 1E chromosome and deploy it in the wheat breeding program.

Maxillofacial growth changes after maxillary protraction therapy in children with class III malocclusion: a dual control group retrospective study.

PURPOSE: To investigate the balance between post-treatment effect and continued nature growth after maxillary protraction treatment in patients with skeletal class III malocclusion. METHODS: 31 patients aged 8.79 ± 1.65 years with skeletal Class III malocclusion had been treated with maxillary protraction and the treatment lasted an average of 1.16 years. The average observation duration after treatment in the maxillary protraction group was 2.05 ± 0.39 years. In the control groups, a sample of 22 patients (9.64 ± 2.53 years) with untreated skeletal class III malocclusion and 24 patients (9.28 ± 0.96 years) with skeletal class I malocclusion were matched to the treatment group according to age, sex and observation period. The mean observation interval of the control groups was 2.39 ± 1.29 years in the class III group and 1.97 ± 0.49 years in the class I group. RESULTS: The active orthopedic treatment effect showed a opposite trend to the natural craniomaxillofacial growth effect after treatment in many aspects. In the observation duration of treatment group, decrease in ANB, Wits appraisal and BAr-AAr were statistically significant compared to class I control group (p < 0.001), and there was a significant increase in NA-FH (P < 0.001) which was contrary to class III control group. Treatment group presented a significant increase in Gn-Co (P < 0.01) and Co-Go (P < 0.001), except for changes in the extent of the mandibular base (Pog-Go, P = 0.149) compared to class I control group. The vertical maxillomandibular skeletal variables (Gonial; MP-SN; MP-FH; Y-axis) in treatment group decreased significantly compared to those in class III control group (P < 0.01). U1-SN and L1-MP showed a significant increase, which was similar to the class I group (P > 0.05), and overjet decreased significantly relative to both of the two control groups (P < 0.05). CONCLUSION: Maxillary protraction therapy led to stable outcomes in approximately 77.42% of children with Class III malocclusion approximately 2 years after treatment. Unfavorable skeletal changes were mainly due to the greater protrusion of the mandible but maxillary protraction did have a certain degree of postimpact on the mandibular base. Protraction therapy does not fundamentally change the mode of maxillary growth in Class III subjects except for the advancement of the maxilla. Craniomaxillofacial region tend to restabilize after treatment and lead to skeletal growth rotation and more dentoalveolar compensation.

[Genetic characterization and drug resistance analysis of Salmonella Kentucky ST314 in Shenzhen in 2010-2021].

OBJECTIVE: To understand the prevalence, genetic characteristics and drug resistance features of Salmonella Kentucky ST314 in Shenzhen. METHODS: Whole genome sequencing of 14 strains of Salmonella Kentucky ST314 collected from 2010-2021 by the Foodborne Disease Surveillance Network of Shenzhen Center for Disease Control and Prevention for phylogenetic evolutionary analysis, drug resistance gene and plasmid detection; drug susceptibility experiments were performed by micro-broth dilution method. RESULTS: A total of 57 strains of Salmonella Kentucky were collected from the foodborne disease surveillance network, 14 of which were ST314. The Shenzhen isolates were clustered with isolates from Southeast Asian countries such as Vietnam and Thailand on clade 314.2, and the single nucleotide polymorphism distance between local strains in Shenzhen was large, indicating dissemination. In this study, a total of 17 drug resistance genes/mutations in 9 categories were detected in the genome of Salmonella Kentucky ST314, carrying 3 extended spectrum beta-lactamases(ESBLs), including bla_(CTX-M-24)(14.3%, 2/14), bla_(CTX-M-55)(7.1%, 1/14), and bla_(CTX-M-130)(14.3%, 2/14), all located on plasmids. Regarding quinolone resistance factors, two plasmid-mediated quinolone resistance(PMQR) genes were identified in the genome: qnrB6(71.4%, 10/14) and aac(6')Ib-cr(78.6%, 11/14), a quinolone resistance quinolone resistance-determining regions(QRDR) mutation T57 S(100%, 14/14). The multi-drug resistance rate of Salmonella Kentucky ST314 in Shenzhen was 92.86%(13/14)with the highest rate of resistance to tetracycline and cotrimoxazole(100%, 14/14), followed by chloramphenicol(92.86%, 13/14), cefotaxime and ampicillin(78.57%, 11/14), ciprofloxacin and nalidixic acid(71.43%, 10/14), and ampicillin-sulbactam had the lowest resistance rate(21.43%, 3/14). CONCLUSION: ST314 is the second most prevalent ST type among Salmonella Kentucky in Shenzhen, mainly isolated from food, especially poultry; phylogenetic analysis suggests that ST314 is a disseminated infection and the genome shows a highly genetically conserved phenotype. Drug resistance of Salmonella Kentucky ST314 is very serious, especially QRDR mutation, PMQR gene co-mediated quinolone resistance and plasmid-mediated cephalosporin resistance are prominent and deserve extensive attention.

Fixed-time angle of attack constrained control for aircraft considering dynamic icing process.

Aircraft icing deteriorates aerodynamic performance and reduces stall angle of attack, the fast convergence rate of tracking error is required to stabilize the aircraft when aircraft icing occurs. The state-of-the-art control methods for icing aircraft mostly assume that the icing of aircraft is instantaneous. Aiming at these issues, a fixed-time angle of attack-constrained control strategy is designed considering dynamic icing process. In order to explore the variation of aerodynamic coefficients in the process of dynamic icing, an ice wind tunnel experiment is implemented, and the relationship between lift coefficient, drag coefficient and pitching moment coefficient with angle of attack and icing intensity is obtained by fitting method. In order to prevent the stalling problem caused by the decrease of the stalling angle of attack in the process of dynamic icing, a method to determine the stalling angle of attack based on deep neural network is proposed. Considering the asymmetric and time-varying angle of attack constraint, a fixed-time convergent angle of attack-constrained robust control method is designed. The ice wind tunnel experiment shows the process of dynamic icing of the airfoil, and the simulation results verify the effectiveness of the proposed control method.

Hemispheric dominance in reading system alters contribution to face processing lateralization across development.

Face processing dominates the right hemisphere. This lateralization can be affected by co-lateralization within the same system and influence between different systems, such as neural competition from reading acquisition. Yet, how the relationship pattern changes through development remains unknown. This study examined the lateralization of core face processing and word processing in different age groups. By comparing fMRI data from 36 school-aged children and 40 young adults, we investigated whether there are age and regional effects on lateralization, and how relationships between lateralization within and between systems change across development. Our results showed significant right hemispheric lateralization in the core face system and left hemispheric lateralization in reading-related areas for both age groups when viewing faces and texts passively. While all participants showed stronger lateralization in brain regions of higher functional hierarchy when viewing faces, only adults exhibited this lateralization when viewing texts. In both age cohorts, there was intra-system co-lateralization for face processing, whereas an inter-system relationship was only found in adults. Specifically, functional lateralization of Broca's area during reading negatively predicted functional asymmetry in the FFA during face perception. This study initially provides neuroimaging evidence for the reading-induced neural competition theory from a maturational perspective in Chinese cohorts.

The potential of RNA methylation in the treatment of cardiovascular diseases.

RNA methylation has emerged as a dynamic regulatory mechanism that impacts gene expression and protein synthesis. Among the known RNA methylation modifications, N6-methyladenosine (m6A), 5-methylcytosine (m5C), 3-methylcytosine (m3C), and N7-methylguanosine (m7G) have been studied extensively. In particular, m6A is the most abundant RNA modification and has attracted significant attention due to its potential effect on multiple biological processes. Recent studies have demonstrated that RNA methylation plays an important role in the development and progression of cardiovascular disease (CVD). To identify key pathogenic genes of CVD and potential therapeutic targets, we reviewed several common RNA methylation and summarized the research progress of RNA methylation in diverse CVDs, intending to inspire effective treatment strategies.

Mushroom-derived bioactive components with definite structures in alleviating the pathogenesis of Alzheimer's disease.

Alzheimer's disease (AD) is a complicated neurodegenerative condition with two forms: familial and sporadic. The familial presentation is marked by autosomal dominance, typically occurring early in individuals under 65 years of age, while the sporadic presentation is late-onset, occurring in individuals over the age of 65. The majority of AD cases are characterized by late-onset and sporadic. Despite extensive research conducted over several decades, there is a scarcity of effective therapies and strategies. Considering the lack of a cure for AD, it is essential to explore alternative natural substances with higher efficacy and fewer side effects for AD treatment. Bioactive compounds derived from mushrooms have demonstrated significant potential in AD prevention and treatment by different mechanisms such as targeting amyloid formation, tau, cholinesterase dysfunction, oxidative stress, neuroinflammation, neuronal apoptosis, neurotrophic factors, ER stress, excitotoxicity, and mitochondrial dysfunction. These compounds have garnered considerable interest from the academic community owing to their advantages of multi-channel, multi-target, high safety and low toxicity. This review focuses on the various mechanisms involved in the development and progression of AD, presents the regulatory effects of bioactive components with definite structure from mushroom on AD in recent years, highlights the possible intervention pathways of mushroom bioactive components targeting different mechanisms, and discusses the clinical studies, limitations, and future perspectives of mushroom bioactive components in AD prevention and treatment.

Boosting Hydrogen Storage Performance of MgH2 by Oxygen Vacancy-Rich H-V2O5 Nanosheet as an Excited H-Pump.

MgH2 is a promising high-capacity solid-state hydrogen storage material, while its application is greatly hindered by the high desorption temperature and sluggish kinetics. Herein, intertwined 2D oxygen vacancy-rich V2O5 nanosheets (H-V2O5) are specifically designed and used as catalysts to improve the hydrogen storage properties of MgH2. The as-prepared MgH2-H-V2O5 composites exhibit low desorption temperatures (Tonset = 185 °C) with a hydrogen capacity of 6.54 wt%, fast kinetics (Ea = 84.55 ± 1.37 kJ mol-1 H2 for desorption), and long cycling stability. Impressively, hydrogen absorption can be achieved at a temperature as low as 30 °C with a capacity of 2.38 wt% within 60 min. Moreover, the composites maintain a capacity retention rate of ~ 99% after 100 cycles at 275 °C. Experimental studies and theoretical calculations demonstrate that the in-situ formed VH2/V catalysts, unique 2D structure of H-V2O5 nanosheets, and abundant oxygen vacancies positively contribute to the improved hydrogen sorption properties. Notably, the existence of oxygen vacancies plays a double role, which could not only directly accelerate the hydrogen ab/de-sorption rate of MgH2, but also indirectly affect the activity of the catalytic phase VH2/V, thereby further boosting the hydrogen storage performance of MgH2. This work highlights an oxygen vacancy excited "hydrogen pump" effect of VH2/V on the hydrogen sorption of Mg/MgH2. The strategy developed here may pave a new way toward the development of oxygen vacancy-rich transition metal oxides catalyzed hydride systems.

Aberrant non-canonical NF-κB signalling reprograms the epigenome landscape to drive oncogenic transcriptomes in multiple myeloma.

In multiple myeloma, abnormal plasma cells establish oncogenic niches within the bone marrow by engaging the NF-κB pathway to nurture their survival while they accumulate pro-proliferative mutations. Under these conditions, many cases eventually develop genetic abnormalities endowing them with constitutive NF-κB activation. Here, we find that sustained NF-κB/p52 levels resulting from such mutations favours the recruitment of enhancers beyond the normal B-cell repertoire. Furthermore, through targeted disruption of p52, we characterise how such enhancers are complicit in the formation of super-enhancers and the establishment of cis-regulatory interactions with myeloma dependencies during constitutive activation of p52. Finally, we functionally validate the pathological impact of these cis-regulatory modules on cell and tumour phenotypes using in vitro and in vivo models, confirming RGS1 as a p52-dependent myeloma driver. We conclude that the divergent epigenomic reprogramming enforced by aberrant non-canonical NF-κB signalling potentiates transcriptional programs beneficial for multiple myeloma progression.

Identification of differentially expressed genes of blood leukocytes for Schizophrenia.

Background: Schizophrenia (SCZ) is a severe neurodevelopmental disorder with brain dysfunction. This study aimed to use bioinformatic analysis to identify candidate blood biomarkers for SCZ. Methods: The study collected peripheral blood leukocyte samples of 9 SCZ patients and 20 healthy controls for RNA sequencing analysis. Bioinformatic analyses included differentially expressed genes (DEGs) analysis, pathway enrichment analysis, and weighted gene co-expression network analysis (WGCNA). Results: This study identified 1,205 statistically significant DEGs, of which 623 genes were upregulated and 582 genes were downregulated. Functional enrichment analysis showed that DEGs were mainly enriched in cell chemotaxis, cell surface, and serine peptidase activity, as well as involved in Natural killer cell-mediated cytotoxicity. WGCNA identified 16 gene co-expression modules, and five modules were significantly correlated with SCZ (p < 0.05). There were 106 upregulated genes and 90 downregulated genes in the five modules. The top ten genes sorted by the Degree algorithm were RPS28, BRD4, FUS, PABPC1, PCBP1, PCBP2, RPL27A, RPS21, RAG1, and RPL27. RAG1 and the other nine genes belonged to the turquoise and pink module respectively. Pathway enrichment analysis indicated that these 10 genes were mainly involved in processes such as Ribosome, cytoplasmic translation, RNA binding, and protein binding. Conclusion: This study finds that the gene functions in key modules and related enrichment pathways may help to elucidate the molecular pathogenesis of SCZ, and the potential of key genes to become blood biomarkers for SCZ warrants further validation.

Small Extracellular Vesicles Laden Oxygen-Releasing Thermosensitive Hydrogel for Enhanced Antibacterial Therapy against Anaerobe-Induced Periodontitis Alveolar Bone Defect.

Periodontitis is a bacterially induced chronic destructive inflammatory disease that leads to irreversible destruction of the tooth supporting structure, including connective tissue destruction, bone resorption, and even tooth loss. Until now, there has been no effective treatment to repair inflammatory bone loss in periodontitis. Recently, small extracellular vesicles (sEVs) emerged as the essential paracrine factors of mesenchymal stem cells (MSCs) that mediated tissue regeneration. However, limitations of antimicrobial activity associated with the use of sEVs have led to the urgency of new alternative strategies. Currently, we investigated the potential of a biocompatible oxygen-releasing thermosensitive hydrogel laded with sEVs secreted by bone marrow MSCs (BMMSCs) for the alveolar bone defect in periodontitis. The hydrogel composed of different polymers such as chitosan (CS), poloxamer 407 (P407), and cross-linked hyaluronic acid (c-HA) conglomerating is a kind of nanoporous structure material. Then, the gel matrix further encapsulated sEVs and calcium peroxide nanoparticles to realize the control of sEVs and oxygen release. Furthermore, ascorbic acid was added to achieve the REDOX equilibrium and acid-base equilibrium. The experiments in vivo and in vitro proved its good biocompatibility and effectively inhibited the growth of the periodontal main anaerobe, relieved periodontal pocket anaerobic infections, and promoted the periodontal defect regeneration. Therefore, this finding demonstrated that it was a promising approach for combating anaerobic pathogens with enhanced and selective properties in periodontal diseases, even in other bacteria-induced infections, for future clinical application.

Comparison of grain traits and genetic diversity between Chinese and Uruguayan soybeans (Glycine max L.).

Soybeans (Glycine max L.), originating in China, were introduced to South America in the late 19th century after passing through North America. South America is now a major soybean-producing region, accounting for approximately 40% of the global soybean production. Crops like soybeans gradually adapt to the local climate and human-selected conditions, resulting in beneficial variations during cultivation in different regions. Comparing the phenotypic and genetic variations in soybeans across different regions is crucial to determining the variations that may enhance soybean productivity. This study identified seed-related traits and conducted a genetic diversity analysis using 46 breeding soybean varieties from China and Uruguay. Compared to the Chinese soybean germplasm, the Uruguayan equivalent had a lower 100-grain weight, higher oil content, lower protein content, and higher soluble sugar content. Using ZDX1 gene chips, genetic typing was performed on the 46 breeding varieties. Cluster analysis based on SNP sites revealed significant differences in the genetic basis of Sino-Uruguayan soybean germplasm. Selection analysis, including nucleotide polymorphism (π) and fixation indexes (Fst), identified several genomic regions under selection between Sino-Uruguayan soybean germplasm. The selected intervals significantly enriched gene ontology (GO) terms related to protein metabolism. Additionally, differentiation occurred in genes associated with the oil content, seed weight, and cyst nematodes between Sino-Uruguayan soybean germplasm, such as GmbZIP123 and GmSSS1. These findings highlight the differences in seed-related phenotypes between Sino-Uruguay soybean germplasm and provide genomic-level insights into the mechanisms behind phenotypic differences, offering valuable references for understanding soybean evolution and molecular breeding.

TWEAK/Fn14 signalling driven super-enhancer reprogramming promotes pro-metastatic metabolic rewiring in triple-negative breast cancer.

Triple Negative Breast Cancer (TNBC) is the most aggressive breast cancer subtype suffering from limited targeted treatment options. Following recent reports correlating Fibroblast growth factor-inducible 14 (Fn14) receptor overexpression in Estrogen Receptor (ER)-negative breast cancers with metastatic events, we show that Fn14 is specifically overexpressed in TNBC patients and associated with poor survival. We demonstrate that constitutive Fn14 signalling rewires the transcriptomic and epigenomic landscape of TNBC, leading to enhanced tumour growth and metastasis. We further illustrate that such mechanisms activate TNBC-specific super enhancers (SE) to drive the transcriptional activation of cancer dependency genes via chromatin looping. In particular, we uncover the SE-driven upregulation of Nicotinamide phosphoribosyltransferase (NAMPT), which promotes NAD+ and ATP metabolic reprogramming critical for filopodia formation and metastasis. Collectively, our study details the complex mechanistic link between TWEAK/Fn14 signalling and TNBC metastasis, which reveals several vulnerabilities which could be pursued for the targeted treatment of TNBC patients.