Graph-based mitochondrial genomes of three foundation species in the Saccharum genus.

KEY MESSAGE: We reported the graph-based mitochondrial genomes of three foundation species (Saccharum spontaneum, S. robustum and S. officinarum) for the first time. The results revealed pan-structural variation and evolutionary processes in the mitochondrial genomes within Saccharum. Saccharum belongs to the Andropogoneae, and cultivars species in Saccharum contribute nearly 80% of sugar production in the world. To explore the genomic studies in Saccharum, we assembled 15 complete mitochondrial genomes (mitogenome) of three foundation species (Saccharum spontaneum, S. robustum and S. officinarum) using Illumina and Oxford Nanopore Technologies sequencing data. The mitogenomes of the three species were divided into a total of eight types based on contig numbers and linkages. All mitogenomes in the three species encoded 51 unique genes, including 32 protein-coding, 3 ribosomal RNA (rRNA) and 16 transfer RNA (tRNA) genes. The existence of long and short-repeat-mediated recombinations in the mitogenome of S. officinarum and S. robustum was revealed and confirmed through PCR validation. Furthermore, employing comparative genomics and phylogenetic analyses of the organelle genomes, we unveiled the evolutionary relationships and history of the major interspecific lineages in Saccharum genus. Phylogenetic analyses of homologous fragments between S. officinarum and S. robustum showed that S. officinarum and S. robustum are phylogenetically distinct and that they were likely parallel rather than domesticated. The variations between ancient (S. sinense and S. barberi) and modern cultivated species (S. hybrid) possibly resulted from hybridization involving different S. officinarum accessions. Lastly, this project reported the first graph-based mitogenomes of three Saccharum species, and a systematic comparison of the structural organization, evolutionary processes, and pan-structural variation of the Saccharum mitogenomes revealed the differential features of the Saccharum mitogenomes.

Exosomes: compositions, biogenesis, and mechanisms in diabetic wound healing.

Diabetic wounds are characterized by incomplete healing and delayed healing, resulting in a considerable global health care burden. Exosomes are lipid bilayer structures secreted by nearly all cells and express characteristic conserved proteins and parent cell-associated proteins. Exosomes harbor a diverse range of biologically active macromolecules and small molecules that can act as messengers between different cells, triggering functional changes in recipient cells and thus endowing the ability to cure various diseases, including diabetic wounds. Exosomes accelerate diabetic wound healing by regulating cellular function, inhibiting oxidative stress damage, suppressing the inflammatory response, promoting vascular regeneration, accelerating epithelial regeneration, facilitating collagen remodeling, and reducing scarring. Exosomes from different tissues or cells potentially possess functions of varying levels and can promote wound healing. For example, mesenchymal stem cell-derived exosomes (MSC-exos) have favorable potential in the field of healing due to their superior stability, permeability, biocompatibility, and immunomodulatory properties. Exosomes, which are derived from skin cellular components, can modulate inflammation and promote the regeneration of key skin cells, which in turn promotes skin healing. Therefore, this review mainly emphasizes the roles and mechanisms of exosomes from different sources, represented by MSCs and skin sources, in improving diabetic wound healing. A deeper understanding of therapeutic exosomes will yield promising candidates and perspectives for diabetic wound healing management.

Associations of sugary beverage consumption with chronic obstructive pulmonary disease (COPD), asthma, and asthma-COPD overlap syndrome: A prospective cohort study.

BACKGROUND: The associations between specific types of sugary beverages and major chronic respiratory diseases remain relatively unexplored. OBJECTIVE: To investigate the associations of sugar-sweetened beverages (SSBs), artificially sweetened beverages (ASBs), and natural juices (NJs) with chronic obstructive pulmonary disease (COPD), asthma, and asthma-COPD overlap syndrome (ACOS). METHODS: This prospective cohort study included 210,339 participants from the UK Biobank. Sugary beverage intake was measured in units (glasses/cans/cartons/250 ml) through 24-hour dietary questionnaires. Logistic regression and Cox proportional hazards models were used to analyze the prevalence and incidence, respectively. Quantile G-computation was employed to estimate the joint associations and relative contributions of the three types of sugary beverages. RESULTS: Over a median follow-up of 11.6 years, 3,491 participants developed COPD, 4,645 asthma, and 523 ACOS. In prevalence analysis, certain categories of SSB and NJ consumption were associated with increased asthma prevalence, while high ASB consumption (>2 units/day) was linked to higher risks of all three outcomes. In incidence analysis, high SSB consumption (>2 units/day) was associated with incident COPD [hazard ratio (HR) 95% confidence interval (CI): 1.53 (1.19, 1.98)] and asthma [HR (95% CI): 1.22 (0.98, 1.52)]. Dose‒response relationships were observed for ASB consumption with all three outcomes [continuous HR (95% CI): 1.98 (1.36, 2.87) for COPD; 1.65 (1.24, 2.20) for asthma; and 2.84 (1.20, 6.72) for ACOS]. Moderate NJ consumption (>0-1 unit/day) was inversely associated with COPD [HR (95% CI): 0.89 (0.82, 0.97)], particularly grapefruit and orange juice. Joint exposure to these beverages (per unit increase) was associated with COPD [HR (95% CI): 1.15 (1.02, 1.29)] and asthma [HR (95% CI): 1.16 (1.06, 1.27)], with ASBs having greater positive weights than SSBs. CONCLUSION: Consumption of SSBs and ASBs was associated with increased risks of COPD, asthma, and potentially ACOS, whereas moderate NJ consumption was associated with a reduced risk of COPD, depending on the juice type.

Recent Advances in Functional Hydrogel for Repair of Abdominal Wall Defects: A Review.

The abdominal wall plays a crucial role in safeguarding the internal organs of the body, serving as an essential protective barrier. Defects in the abdominal wall are common due to surgery, infection, or trauma. Complex defects have limited self-healing capacity and require external intervention. Traditional treatments have drawbacks, and biomaterials have not fully achieved the desired outcomes. Hydrogel has emerged as a promising strategy that is extensively studied and applied in promoting tissue regeneration by filling or repairing damaged tissue due to its unique properties. This review summarizes the five prominent properties and advances in using hydrogels to enhance the healing and repair of abdominal wall defects: (a) good biocompatibility with host tissues that reduces adverse reactions and immune responses while supporting cell adhesion migration proliferation; (b) tunable mechanical properties matching those of the abdominal wall that adapt to normal movement deformations while reducing tissue stress, thereby influencing regulating cell behavior tissue regeneration; (c) drug carriers continuously delivering drugs and bioactive molecules to sites optimizing healing processes enhancing tissue regeneration; (d) promotion of cell interactions by simulating hydrated extracellular matrix environments, providing physical support, space, and cues for cell migration, adhesion, and proliferation; (e) easy manipulation and application in surgical procedures, allowing precise placement and close adhesion to the defective abdominal wall, providing mechanical support. Additionally, the advances of hydrogels for repairing defects in the abdominal wall are also mentioned. Finally, an overview is provided on the current obstacles and constraints faced by hydrogels, along with potential prospects in the repair of abdominal wall defects.

Hybrid Double-Sided Tape with Asymmetrical Adhesion and Burst Pressure Tolerance for Abdominal Injury Treatment.

Patients with open abdominal (OA) wounds have a mortality risk of up to 30%, and the resulting disabilities would have profound effects on patients. Here, we present a novel double-sided adhesive tape developed for the management of OA wounds. The tape features an asymmetrical structure and employs an acellular dermal matrix (ADM) with asymmetric wettability as a scaffold. It is constructed by integrating a tissue-adhesive hydrogel composed of polydopamine (pDA), quaternary ammonium chitosan (QCS), and acrylic acid cross-linking onto the bottom side of the ADM. Following surface modification with pDA, the ADM would exhibit characteristics resistant to bacterial adhesion. Furthermore, the presence of a developed hydrogel ensures that the tape not only possesses tissue adhesiveness and noninvasive peelability but also effectively mitigates damage caused by oxidative stress. Besides, the ADM inherits the strength of the skin, imparting high burst pressure tolerance to the tape. Based on these remarkable attributes, we demonstrate that this double-sided (D-S) tape facilitates the repair of OA wounds, mitigates damage to exposed intestinal tubes, and reduces the risk of intestinal fistulae and complications. Additionally, the D-S tape is equally applicable to treating other abdominal injuries, such as gastric perforations. It effectively seals the perforation, promotes injury repair, and prevents the formation of postoperative adhesions. These notable features indicate that the presented double-sided tape holds significant potential value in the biomedical field.

Highly efficient anion exchange membrane water electrolyzers via chromium-doped amorphous electrocatalysts.

In-depth comprehension and modulation of the electronic structure of the active metal sites is crucial to enhance their intrinsic activity of electrocatalytic oxygen evolution reaction (OER) toward anion exchange membrane water electrolyzers (AEMWEs). Here, we elaborate a series of amorphous metal oxide catalysts (FeCrOx, CoCrOx and NiCrOx) with high performance AEMWEs by high-valent chromium dopant. We discover that the positive effect of the transition from low to high valence of the Co site on the adsorption energy of the intermediate and the lower oxidation barrier is the key factor for its increased activity by synchrotron radiation in-situ techniques. Particularly, the CoCrOx anode catalyst achieves the high current density of 1.5 A cm-2 at 2.1 V and maintains for over 120 h with attenuation less than 4.9 mV h-1 in AEMWE testing. Such exceptional performance demonstrates a promising prospect for industrial application and providing general guidelines for the design of high-efficiency AEMWEs systems.

Long-term exposure to fine particulate matter constituents in relation to chronic kidney disease: evidence from a large population-based study in China.

The effects of long-term exposure to fine particulate matter (PM2.5) constituents on chronic kidney disease (CKD) are not fully known. This study sought to examine the association between long-term exposure to major PM2.5 constituents and CKD and look for potential constituents contributing substantially to CKD. This study included 81,137 adults from the 2018 to 2019 baseline survey of China Multi-Ethnic Cohort. CKD was defined by the estimated glomerular filtration rate. Exposure concentration data of 7 major PM2.5 constituents were assessed by satellite remote sensing. Logistic regression models were used to estimate the effect of each PM2.5 constituent exposure on CKD. The weighted quantile sum regression was used to estimate the effect of mixed exposure to all constituents. PM2.5 constituents had positive correlations with CKD (per standard deviation increase), with ORs (95% CIs) of 1.20 (1.02-1.41) for black carbon, 1.27 (1.07-1.51) for ammonium, 1.29 (1.08-1.55) for nitrate, 1.20 (1.01-1.43) for organic matter, 1.25 (1.06-1.46) for sulfate, 1.30 (1.11-1.54) for soil particles, and 1.63 (1.39-1.91) for sea salt. Mixed exposure to all constituents was positively associated with CKD (1.68, 1.32-2.11). Sea salt was the constituent with the largest weight (0.36), which suggested its importance in the PM2.5-CKD association, followed by nitrate (0.32), organic matter (0.18), soil particles (0.10), ammonium (0.03), BC (0.01). Sulfate had the least weight (< 0.01). Long-term exposure to PM2.5 sea salt and nitrate may contribute more than other constituents in increasing CKD risk, providing new evidence and insights for PM2.5-CKD mechanism research and air pollution control strategy.

Endothelial peroxiredoxin-4 is indispensable for blood-brain barrier integrity and long-term functional recovery after ischemic stroke.

The endothelial lining of cerebral microvessels is damaged relatively early after cerebral ischemia/reperfusion (I/R) injury and mediates blood-brain barrier (BBB) disruption, neurovascular injury, and long-term neurological deficits. I/R induces BBB leakage within 1 h due to subtle structural alterations in endothelial cells (ECs), including reorganization of the actin cytoskeleton and subcellular redistribution of junctional proteins. Herein, we show that the protein peroxiredoxin-4 (Prx4) is an endogenous protectant against endothelial dysfunction and BBB damage in a murine I/R model. We observed a transient upregulation of Prx4 in brain ECs 6 h after I/R in wild-type (WT) mice, whereas tamoxifen-induced, selective knockout of Prx4 from endothelial cells (eKO) mice dramatically raised vulnerability to I/R. Specifically, eKO mice displayed more BBB damage than WT mice within 1 to 24 h after I/R and worse long-term neurological deficits and focal brain atrophy by 35 d. Conversely, endothelium-targeted transgenic (eTG) mice overexpressing Prx4 were resistant to I/R-induced early BBB damage and had better long-term functional outcomes. As demonstrated in cultures of human brain endothelial cells and in animal models of I/R, Prx4 suppresses actin polymerization and stress fiber formation in brain ECs, at least in part by inhibiting phosphorylation/activation of myosin light chain. The latter cascade prevents redistribution of junctional proteins and BBB leakage under conditions of Prx4 repletion. Prx4 also tempers microvascular inflammation and infiltration of destructive neutrophils and proinflammatory macrophages into the brain parenchyma after I/R. Thus, the evidence supports an indispensable role for endothelial Prx4 in safeguarding the BBB and promoting functional recovery after I/R brain injury.

Remediation of crude oil contaminated soil through an integrated biological-chemical-biological strategy.

A plausible approach to remediating petroleum contaminated soil is the integration of chemical and biological treatments. Using appropriate chemical oxidation, the integrated remediation can be effectively achieved to stimulate the biodegradation process, consequently bolstering the overall remediation effect. In this study, an integrated biological-chemical-biological strategy was proposed. Both conventional microbial degradation techniques and a modified Fenton method were employed, and the efficacy of this strategy on crude oil contaminated soil, as well as its impact on pollutant composition, soil environment, and soil microorganism, was assessed. The results showed that this integrated remediation realized an overall 68.3 % removal rate, a performance 1.7 times superior to bioremediation alone and 2.1 times more effective than chemical oxidation alone, elucidating that the biodegradation which had become sluggish was invigorated by the judicious application of chemical oxidation. By optimizing the positioning of chemical treatment, the oxidization was allowed to act predominantly on refractory substances like resins, thus effectively enhancing pollutant biodegradability. Concurrently, this oxidating maneuver contributed to a significant increase in concentrations of dissolvable nutrients while maintaining appropriate soil pH levels, thereby generating favorable growth conditions for microorganism. Moreover, attributed to the proliferation and accumulation of degrading bacteria during the initial bioremediation phase, the microbial growth subsequent to oxidation showed rapid resurgence and the relative abundance of typical petroleum-degrading bacteria, particularly Proteobacteria, was substantially increased, which played a significant role in enhancing overall remediation effect. Our research validated the feasibility of biological-chemical-biological strategy and elucidated its correlating mechanisms, presenting a salient reference for the further studies concerning the integrated remediation of petroleum contaminated soil.

Advancements in hydrogel-based drug delivery systems for the treatment of inflammatory bowel disease: a review.

Inflammatory bowel disease (IBD) is a chronic disorder that affects millions of individuals worldwide. However, current drug therapies for IBD are plagued by significant side effects, low efficacy, and poor patient compliance. Consequently, there is an urgent need for novel therapeutic approaches to alleviate IBD. Hydrogels, three-dimensional networks of hydrophilic polymers with the ability to swell and retain water, have emerged as promising materials for drug delivery in the treatment of IBD due to their biocompatibility, tunability, and responsiveness to various stimuli. In this review, we summarize recent advancements in hydrogel-based drug delivery systems for the treatment of IBD. We first identify three pathophysiological alterations that need to be addressed in the current treatment of IBD: damage to the intestinal mucosal barrier, dysbiosis of intestinal flora, and activation of inflammatory signaling pathways leading to disequilibrium within the intestines. Subsequently, we discuss in depth the processes required to prepare hydrogel drug delivery systems, from the selection of hydrogel materials, types of drugs to be loaded, methods of drug loading and drug release mechanisms to key points in the preparation of hydrogel drug delivery systems. Additionally, we highlight the progress and impact of the hydrogel-based drug delivery system in IBD treatment through regulation of physical barrier immune responses, promotion of mucosal repair, and improvement of gut microbiota. In conclusion, we analyze the challenges of hydrogel-based drug delivery systems in clinical applications for IBD treatment, and propose potential solutions from our perspective.

Highly dispersed ultrafine PtCo alloy nanoparticles on unique composite carbon supports for proton exchange membrane fuel cells.

The design of highly efficient and robust platinum-based electrocatalysts is pivotal for proton exchange membrane fuel cells (PEMFC). One of the long-standing issues for PEMFC is the rapid deactivation of the catalyst under working conditions. Here, we report a simple synthesis strategy for ultrafine PtCo alloy nanoparticles loaded on a unique carbon support derived from a zeolitic imidazolate framework-67 (ZIF-67) and Ketjen Black (KB) composite, exhibiting a remarkable catalytic performance toward the oxygen reduction reaction (ORR) and PEMFC. Benefitting from the N-doping and wide pore size distribution of the composite carbon supports, the growth of PtCo nanoparticles can be evenly restricted, leading to a uniform distribution. The Pt-integrated catalyst delivers an outstanding electrochemical performance with a mass activity that is 8.6 times higher than that of the commercial Pt/C catalyst. Impressively, the accelerated durability test (ADT) demonstrates that the hybrid carbon support can significantly enhance the durability. Theoretical simulations highlight the synergistic contribution between the supports and the PtCo nanoparticles. Moreover, hydrogen-oxygen fuel cells assembled with the catalyst exhibited a high power density of 1.83 W cm-2 at 4 A cm-2. These results provide a new opportunity to design advanced catalysts for PEMFC.

Monophenylboryl aza-BODIPY with free rotation of the B-phenyl group for enhanced photothermal conversion.

Owing to the efficient non-radiative relaxation by the free rotation of the B-phenyl moiety, monophenyl substituted aza-BODIPY on the boron centre with near-infrared absorption has high photothermal conversion efficiency, which is highly desirable for a photothermal therapy agent.

High power tunable Raman fiber laser at 1.2 µm waveband.

Development of a high power fiber laser at special waveband, which is difficult to achieve by conventional rare-earth-doped fibers, is a significant challenge. One of the most common methods for achieving lasing at special wavelength is Raman conversion. Phosphorus-doped fiber (PDF), due to the phosphorus-related large frequency shift Raman peak at 40 THz, is a great choice for large frequency shift Raman conversion. Here, by adopting 150 m large mode area triple-clad PDF as Raman gain medium, and a novel wavelength-selective feedback mechanism to suppress the silica-related Raman emission, we build a high power cladding-pumped Raman fiber laser at 1.2 µm waveband. A Raman signal with power up to 735.8 W at 1252.7 nm is obtained. To the best of our knowledge, this is the highest output power ever reported for fiber lasers at 1.2 µm waveband. Moreover, by tuning the wavelength of the pump source, a tunable Raman output of more than 450 W over a wavelength range of 1240.6-1252.7 nm is demonstrated. This work proves PDF's advantage in high power large frequency shift Raman conversion with a cladding pump scheme, thus providing a good solution for a high power laser source at special waveband.

In situ bioprinting of double network anti-digestive xanthan gum derived hydrogel scaffolds for the treatment of enterocutaneous fistulas.

The clinical treatment of enterocutaneous fistula is challenging and causes significant patient discomfort. Fibrin gel can be used to seal tubular enterocutaneous fistulas, but it has low strength and poor digestion resistance. Based on in situ bioprinting and the anti-digestive properties of xanthan gum (XG), we used carboxymethyl chitosan (CMC) and xanthan gum modified by grafted glycidyl methacrylate (GMA) and aldehyde (GCX) as the ink to print a double network hydrogel that exhibited high strength and an excellent anti-digestive performance. In addition, in vitro studies confirmed the biocompatibility, degradability, and self-healing of hydrogels. In our rabbit tubular enterocutaneous fistula model, the in situ printed hydrogel resisted corrosion due to the intestinal fluid and acted as a scaffold for intestinal mucosal cells to proliferate on its surface. To summarize, in situ bioprinting GCX/CMC double network hydrogel can effectively block tubular enterocutaneous fistulas and provide a stable scaffold for intestinal mucosal regeneration.

Establishment and evaluation of an improved rat model of open abdomen.

INTRODUCTION: This study aimed to establish an animal model of open abdomen (OA) through temporary abdominal closure via different techniques. METHODS: Adult male Sprague-Dawley rats were randomly divided into three groups: group A (OA with polypropylene mesh alone); group B (OA with polypropylene mesh combined with a patch); and group C (OA with polypropylene mesh and a sutured patch). Vital signs, pathophysiological changes, and survival rates were closely monitored in the rats for 7 days after surgery. Abdominal X-rays and histopathological examinations were performed to assess abdominal organ changes and wound healing. RESULTS: The results showed no significant difference in mortality rates among the three groups (p > 0.05). However, rats in group B exhibited superior overall condition, cleaner wounds, and a higher rate of wound healing compared to the other groups (p < 0.05). Abdominal X-rays indicated that varying degrees of distal intestinal obstruction in all groups. Histopathological examinations revealed fibrous hyperplasia, inflammatory cell infiltration, neovascularization, and collagen deposition in all groups. Group B demonstrated enhanced granulation tissue generation, neovascularization, and collagen deposition compared to the other groups (p < 0.05). CONCLUSIONS: Polypropylene mesh combined with patches is the most suitable method for establishing an animal model of OA. This model successfully replicated the pathological and physiological changes in postoperative patients with OA, specifically the progress of abdominal skin wound healing. It provides a practical and reliable animal model for OA research.

Ferroptosis: the emerging player in remodeling triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a highly heterogeneous breast tumor type that is highly malignant, invasive, and highly recurrent. Ferroptosis is a unique mode of programmed cell death (PCD) at the morphological, physiological, and molecular levels, mainly characterized by cell death induced by iron-dependent accumulation of lipid peroxides, which plays a substantial role in a variety of diseases, including tumors and inflammatory diseases. TNBC cells have been reported to display a peculiar equilibrium metabolic profile of iron and glutathione, which may increase the sensitivity of TNBC to ferroptosis. TNBC possesses a higher sensitivity to ferroptosis than other breast cancer types. Ferroptosis also occurred between immune cells and tumor cells, suggesting that regulating ferroptosis may remodel TNBC by modulating the immune response. Many ferroptosis-related genes or molecules have characteristic expression patterns and are expected to be diagnostic targets for TNBC. Besides, therapeutic strategies based on ferroptosis, including the isolation and extraction of natural drugs and the use of ferroptosis inducers, are urgent for TNBC personalized treatment. Thus, this review will explore the contribution of ferroptosis in TNBC progression, diagnosis, and treatment, to provide novel perspectives and therapeutic strategies for TNBC management.

A click chemistry-mediated all-peptide cell printing hydrogel platform for diabetic wound healing.

High glucose-induced vascular endothelial injury is a major pathological factor involved in non-healing diabetic wounds. To interrupt this pathological process, we design an all-peptide printable hydrogel platform based on highly efficient and precise one-step click chemistry of thiolated γ-polyglutamic acid, glycidyl methacrylate-conjugated γ-polyglutamic acid, and thiolated arginine-glycine-aspartate sequences. Vascular endothelial growth factor 165-overexpressed human umbilical vein endothelial cells are printed using this platform, hence fabricating a living material with high cell viability and precise cell spatial distribution control. This cell-laden hydrogel platform accelerates the diabetic wound healing of rats based on the unabated vascular endothelial growth factor 165 release, which promotes angiogenesis and alleviates damages on vascular endothelial mitochondria, thereby reducing tissue hypoxia, downregulating inflammation, and facilitating extracellular matrix remodeling. Together, this study offers a promising strategy for fabricating tissue-friendly, high-efficient, and accurate 3D printed all-peptide hydrogel platform for cell delivery and self-renewable growth factor therapy.

Long-term exposure to ambient PM2.5 and its constituents is associated with MAFLD.

Background & Aims: Existing evidence suggests that long-term exposure to ambient fine particulate pollution (PM2.5) may increase metabolic dysfunction-associated fatty liver disease (MAFLD) risk. However, there is still limited evidence on the association of PM2.5 constituents with MAFLD. Therefore, this study explores the associations between the five main chemical constituents of PM2.5 and MAFLD to provide more explicit information on the liver exposome. Methods: A total of 76,727 participants derived from the China Multi-Ethnic Cohort, a large-scale epidemic survey in southwest China, were included in this study. Multiple linear regression models were used to estimate the pollutant-specific association with MAFLD. Weighted quantile sum regression was used to evaluate the joint effect of the pollutant-mixture on MAFLD and identify which constituents contribute most to it. Results: Three-year exposure to PM2.5 constituents was associated with a higher MAFLD risk and more severe liver fibrosis. Odds ratios for MAFLD were 1.480, 1.426, 1.294, 1.561, 1.618, and 1.368 per standard deviation increase in PM2.5, black carbon, organic matter, ammonium, sulfate, and nitrate, respectively. Joint exposure to the five major chemical constituents was also positively associated with MAFLD (odds ratio 1.490, 95% CI 1.360-1.632). Nitrate contributed most to the joint effect of the pollutant-mixture. Further stratified analyses indicate that males, current smokers, and individuals with a high-fat diet might be more susceptible to ambient PM2.5 exposure than others. Conclusions: Long-term exposure to PM2.5 and its five major chemical constituents may increase the risk of MAFLD. Nitrate might contribute most to MAFLD, which may provide new clues for liver health. Males, current smokers, and participants with high-fat diets were more susceptible to these associations. Impact and implications: This large-scale epidemiologic study explored the associations between constituents of fine particulate pollution (PM2.5) and metabolic dysfunction-associated fatty liver disease (MAFLD), and further revealed which constituents play a more important role in increasing the risk of MAFLD. In contrast to previous studies that examined the effects of PM2.5 as a whole substance, this study carefully explored the health effects of the individual constituents of PM2.5. These findings could (1) help researchers to identify the specific particles responsible for hepatotoxicity, and (2) indicate possible directions for policymakers to efficiently control ambient air pollution, such as targeting the sources of nitrate pollution.

Itaconate inhibits SYK through alkylation and suppresses inflammation against hvKP induced intestinal dysbiosis.

Hypervirulent Klebsiella pneumoniae (hvKP) is a highly lethal opportunistic pathogen that elicits more severe inflammatory responses compared to classical Klebsiella pneumoniae (cKP). In this study, we investigated the interaction between hvKP infection and the anti-inflammatory immune response gene 1 (IRG1)-itaconate axis. Firstly, we demonstrated the activation of the IRG1-itaconate axis induced by hvKP, with a dependency on SYK signaling rather than STING. Importantly, we discovered that exogenous supplementation of itaconate effectively inhibited excessive inflammation by directly inhibiting SYK kinase at the 593 site through alkylation. Furthermore, our study revealed that itaconate effectively suppressed the classical activation phenotype (M1 phenotype) and macrophage cell death induced by hvKP. In vivo experiments demonstrated that itaconate administration mitigated hvKP-induced disturbances in intestinal immunopathology and homeostasis, including the restoration of intestinal barrier integrity and alleviation of dysbiosis in the gut microbiota, ultimately preventing fatal injury. Overall, our study expands the current understanding of the IRG1-itaconate axis in hvKP infection, providing a promising foundation for the development of innovative therapeutic strategies utilizing itaconate for the treatment of hvKP infections.

Genome-Wide Association Study Unravels Quantitative Trait Loci and Genes Associated with Yield-Related Traits in Sugarcane.

Sugarcane, a major sugar and energy crop worldwide faces an increasing demand for higher yields. Identifying yield-related markers and candidate genes is valuable for breeding high-yield varieties using molecular techniques. In this work, seven yield-related traits were evaluated in a diversity panel of 159 genotypes, derived from Tripidium arundinaceum, Saccharum spontaneum, and modern sugarcane genotypes. All traits exhibited significant genetic variance with high heritability and high correlations. Genetic diversity analysis reveals a genomic decay of 23 kb and an average single nucleotide polymorphism (SNP) number of 25,429 per genotype. These 159 genotypes were divided into 4 subgroups. Genome-wide association analysis identified 47 SNPs associated with brix, spanning 36 quantitative trait loci (QTLs), and 138 SNPs for other traits across 104 QTLs, covering all 32 chromosomes. Interestingly, 12 stable QTLs associated with yield-related traits were identified, which contained 35 candidate genes. This work provides markers and candidate genes for marker-assisted breeding to improve sugarcane yields.