Effects of soy protein isolate interaction with brown rice starch on the multiscale structure of brown rice bread.

BACKGROUND: Gluten-free bread (GFB) has technical bottlenecks such as hard texture, rough taste and low nutrition in practical production. In order to solve these problems, this study used germinated brown rice starch as the main raw material, and investigated the effects of soybean isolate protein (SPI) on the multiscale structure of germinated brown rice starch and bread quality. RESULTS: A gluten-free rice bread process simulation system was established, and the interaction between SPI and starch in the simulation system was characterized. The result shows that the interaction forces between SPI and germinated brown rice starch were mainly represented by hydrogen bonds, and with the addition of SPI, the crystallinity of starch showed a downward trend. At the same time, when the amount of SPI was 3%, the appearance quality was the best and the specific volume of bread was 1.08 mL g-1. When the amount of SPI was 6%, the texture quality was the best. Compared with the bread without SPI, the hardness of the bread with 6% SPI was reduced by 0.13 times, the springiness was increased by 0.03 times, the color was the most vibrant, the L* value being 1.02 times the original, and the baking loss was reduced to 0.98 times the original. CONCLUSIONS: The interaction force between SPI and germinated brown rice starch and its effect on bread quality were clarified, and these results inform choices about providing a theoretical basis for the subsequent development of higher-quality GFB. © 2024 Society of Chemical Industry.

Peering through the hedge: Multiple datasets yield insights into the phylogenetic relationships and incongruences in the tribe Lilieae (Liliaceae).

The increasing use of genome-scale data has significantly facilitated phylogenetic analyses, contributing to the dissection of the underlying evolutionary mechanisms that shape phylogenetic incongruences, such as incomplete lineage sorting (ILS) and hybridization. Lilieae, a prominent member of the Liliaceae family, comprises four genera and approximately 260 species, representing 43% of all species within Liliaceae. They possess high ornamental, medicinal and edible values. Yet, no study has explored the validity of various genome-scale data in phylogenetic analyses within this tribe, nor have potential evolutionary mechanisms underlying its phylogenetic incongruences been investigated. Here, transcriptome, Angiosperms353, plastid and mitochondrial data, were collected from 50 to 93 samples of Lilieae, covering all four recognized genera. Multiple datasets were created and used for phylogenetic analyses based on concatenated and coalescent-based methods. Evolutionary rates of different datasets were calculated, and divergence times were estimated. Various approaches, including coalescence simulation, Quartet Sampling (QS), calculation of concordance factors (gCF and sCF), as well as MSCquartets and reticulate network inference, were carried out to infer the phylogenetic discordances and analyze their underlying mechanisms using a reduced 33-taxon dataset. Despite extensive phylogenetic discordances among gene trees, robust phylogenies were inferred from nuclear and plastid data compared to mitochondrial data, with lower synonymous substitution detected in mitochondrial genes than in nuclear and plastid genes. Significant ILS was detected across the phylogeny of Lilieae, with clear evidence of reticulate evolution identified. Divergence time estimation indicated that most of lineages in Lilieae diverged during a narrow time frame (ranging from 5.0 Ma to 10.0 Ma), consistent with the notion of rapid radiation evolution. Our results suggest that integrating transcriptomic and plastid data can serve as cost-effective and efficient tools for phylogenetic inference and evolutionary analysis within Lilieae, and Angiosperms353 data is also a favorable choice. Mitochondrial data are more suitable for phylogenetic analyses at higher taxonomic levels due to their stronger conservation and lower synonymous substitution rates. Significant phylogenetic incongruences detected in Lilieae were caused by both incomplete lineage sorting (ILS) and reticulate evolution, with hybridization and "ghost introgression" likely prevalent in the evolution of Lilieae species. Our findings provide new insights into the phylogeny of Lilieae, enhancing our understanding of the evolution of species in this tribe.

Phylogeny, adaptive evolution, and taxonomy of Acronema (Apiaceae): evidence from plastid phylogenomics and morphological data.

Introduction: The genus Acronema, belonging to Apiaceae, includes approximately 25 species distributed in the high-altitude Sino-Himalayan region from E Nepal to SW China. This genus is a taxonomically complex genus with often indistinct species boundaries and problematic generic delimitation with Sinocarum and other close genera, largely due to the varied morphological characteristics. Methods: To explore the phylogenetic relationships and clarify the limits of the genus Acronema and its related genera, we reconstructed a reliable phylogenetic framework with high support and resolution based on two molecular datasets (plastome data and ITS sequences) and performed morphological analyses. Results: Both phylogenetic analyses robustly supported that Acronema was a non-monophyletic group that fell into two clades: Acronema Clade and East-Asia Clade. We also newly sequenced and assembled sixteen Acronema complete plastomes and performed comprehensively comparative analyses for this genus. The comparative results showed that the plastome structure, gene number, GC content, codon bias patterns were high similarity, but varied in borders of SC/IR and we identified six different types of SC/IR border. The SC/IR boundaries of Acronema chienii were significantly different from the other Acronema members which was consistent with the type VI pattern in the genus Tongoloa. We also identified twelve potential DNA barcode regions (ccsA, matK, ndhF, ndhG, psaI, psbI, rpl32, rps15, ycf1, ycf3, psaI-ycf4 and psbM-trnD) for species identification in Acronema. The molecular evolution of Acronema was relatively conservative that only one gene (petG) was found to be under positive selection (ω = 1.02489). Discussion: The gene petG is one of the genes involved in the transmission of photosynthetic electron chains during photosynthesis, which plays a crucial role in the process of photosynthesis in plants. This is also a manifestation of the adaptive evolution of plants in high-altitude areas to the environment. In conclusion, our study provides novel insights into the plastome adaptive evolution, phylogeny, and taxonomy of genus Acronema.

Inhibition of inflammatory osteoclasts accelerates callus remodeling in osteoporotic fractures by enhancing CGRP+TrkA+ signaling.

Impaired callus remodeling significantly contributes to the delayed healing of osteoporotic fractures; however, the underlying mechanisms remain unclear. Sensory neuronal signaling plays a crucial role in bone repair. In this study, we aimed to investigate the pathological mechanisms hindering bone remodeling in osteoporotic fractures, particularly focusing on the role of sensory neuronal signaling. We demonstrate that in ovariectomized (OVX) mice, the loss of CGRP+TrkA+ sensory neuronal signaling during callus remodeling correlates with increased Cx3cr1+iOCs expression within the bone callus. Conditional knockout of Cx3cr1+iOCs restored CGRP+TrkA+ sensory neuronal, enabling normal callus remodeling progression. Mechanistically, we further demonstrate that Cx3cr1+iOCs secrete Sema3A in the osteoporotic fracture repair microenvironment, inhibiting CGRP+TrkA+ sensory neurons' axonal regeneration and suppressing nerve-bone signaling exchange, thus hindering bone remodeling. Lastly, in human samples, we observed an association between the loss of CGRP+TrkA+ sensory neuronal signaling and increased expression of Cx3cr1+iOCs. In conclusion, enhancing CGRP+TrkA+ sensory nerve signaling by inhibiting Cx3cr1+iOCs activity presents a potential strategy for treating delayed healing in osteoporotic fractures. Inhibition of inflammatory osteoclasts enhances CGRP+TrkA+ signaling and accelerates callus remodeling in osteoporotic fractures.

Light-Up Fluorescence and Circularly Polarized Luminescence in Achiral Interlocked Framework via Adaptive Lone Pair-π Interaction Confinement.

Interactions between lone pairs and aromatic π systems are significant across biology and self-assembled materials. Herein, employing an achiral confinement metal-organic framework (MOF) encapsulates guest molecules, it is successfully realized that lone pair (lp)-π interaction induces fluorescence "turn-on" and circularly polarized luminescence for the first time. The MOFs synthesized based on naphthalenediimide show nearly non-emissive, which can be light-up by introducing acetone or ester guests containing lone pairs-π interaction. Furthermore, the introduction of a series of lp-rich chiral esters induces supramolecular chirality as well as circularly polarized luminescence in achiral MOFs, while also observing chiral adaptability. This work first demonstrates the luminescence and chiral induction via lone pair electrons-π interactions, presenting a fresh paradigm for the advancement of chiroptical materials.

Glioma stem cells remodel immunotolerant microenvironment in GBM and are associated with therapeutic advancements.

Glioma is the most common primary tumor of the central nervous system (CNS). Glioblastoma (GBM) is incurable with current treatment strategies. Additionally, the treatment of recurrent GBM (rGBM) is often referred to as terminal treatment, necessitating hospice-level care and management. The presence of the blood-brain barrier (BBB) gives GBM a more challenging or "cold" tumor microenvironment (TME) than that of other cancers and gloma stem cells (GSCs) play an important role in the TME remodeling, occurrence, development and recurrence of giloma. In this review, our primary focus will be on discussing the following topics: niche-associated GSCs and macrophages, new theories regarding GSC and TME involving pyroptosis and ferroptosis in GBM, metabolic adaptations of GSCs, the influence of the cold environment in GBM on immunotherapy, potential strategies to transform the cold GBM TME into a hot one, and the advancement of GBM immunotherapy and GBM models.

Effect of 5:2 intermittent fasting diet versus daily calorie restriction eating on metabolic-associated fatty liver disease-a randomized controlled trial.

Objective: Both 5:2 IF diet (intermittent fasting) and daily caloric restriction eating had been suggested for management of MAFLD (Metabolic-Associated Fatty Liver Disease), this study aimed to evaluate the effects of 5:2 IF diet on body weight and metabolic parameters in adults with MAFLD, in comparison to daily caloric restriction eating. Methods: This single-center, double-blind, prospective, randomized controlled trial included 60 patients with MAFLD, who were administered either a 5:2 IF diet limited calories consumed for 2 days each week with no restrictions on the remaining 5 (Group 5:2 IF diet) or a daily calorie restriction eating (Group daily calorie restriction). Fibrotouch-B instrument assessment, ultrasound assessment of hepatic steatosis, anthropometric indices and body composition analysis, blood sample measurements were conducted during two distinct visits: initially on the day of study commencement (T1), and subsequently at the conclusion of the 12-week intervention period (T2). Results: In comparison to daily calorie restriction eating, the 5:2 IF diet significantly decreased the proportion of hepatic steatosis ≥moderate (29.6% vs. 59.3%, p = 0.028) and the degree of hepatic fibrosis F ≥ 2 (3.7% vs. 25.9%, p = 0.05), and fewer percentage of patients were diagnosed with fatty liver via upper abdominal ultrasound in the 5:2 intermittent fasting diet group (33.3% vs. 63.0%, p = 0.029). Additionally, the CAP (controlled attenuation parameter) and LSM (liver stiffness measurements) value were significantly lower in the 5:2 IF diet group (p < 0.05). No statistically significant differences were observed between the two groups in terms of weight, BMI (body mass index), WC (waist circumference), HC (hip circumference), and WHR (waist to hip ratio). Similarly, there were no significant differences in lipid profile, glycemic indices and adverse events (p > 0.05). Conclusion: In summary, although both 5:2 IF diet and daily caloric restriction eating achieved similar effect on body weight, liver enzymes, lipid profile and glycemic indices after 12 weeks treatment, 5:2 IF diet demonstrates better improvement in fibrosis and steatosis scores independently from weight regulation. Consequently, it is anticipated to emerge as a viable dietary modality for lifestyle intervention among patients diagnosed with MAFLD. Clinical trial registration: https://www.crd.york.ac.uk/PROSPERO, identifier ChiCTR2400080292.

Au@Pd nanozyme-mediated catalytic therapy: a novel strategy for targeting tumor microenvironment in cancer treatment.

BACKGROUND: Breast cancer, with its high morbidity and mortality rates, is a significant global health burden. Traditional treatments-surgery, chemotherapy, and radiotherapy-are widely used but come with drawbacks such as recurrence, metastasis, and significant side effects, including damage to healthy tissues. To address these limitations, new therapeutic strategies are being developed. Peroxidases (POD) can catalyze excess H2O2 in the tumor microenvironment to generate reactive oxygen species (ROS), which induce cancer cell apoptosis by disrupting redox homeostasis and modulating apoptosis-related proteins. However, natural enzymes face challenges like poor stability, high cost, and sensitivity to environmental conditions, limiting their application in breast cancer treatment. Nanozymes, nanomaterials with enzyme-like activity, offer a promising alternative by overcoming these limitations. METHODS: In this study, we successfully prepared Au@Pd nanozymes with peroxidase activity by depositing metallic Pd on Au nanoparticles (Au NPs) synthesized using a trisodium citrate reduction method and ascorbic acid reduction. The in vitro validation was conducted through a series of experiments, including ROS detection, flow cytometry, CCK-8 assay, DNA damage assessment, live/dead cell staining, Western blot (WB), and qPCR. Tumor treatment was performed via tail vein injection of the drug, followed by HE staining of the treated tissues and biochemical analysis of the blood. RESULTS: Au@Pd nanozymes can effectively accumulate at the tumor site through the EPR effect and exert peroxidase-like activity, catalyzing the excess H2O2 in the tumor microenvironment to produce ROS. This triggers apoptosis pathways and DNA damage, leading to the downregulation of the anti-apoptotic protein Bcl-2, upregulation of the pro-apoptotic protein Bax, and induction of apoptosis-related genes, demonstrating strong anti-tumor effects. CONCLUSIONS: This study developed an efficient nanozyme-mediated catalytic therapy strategy targeting the tumor microenvironment for the treatment of breast cancer cells.

Oncolytic herpes simplex virus propagates tertiary lymphoid structure formation via CXCL10/CXCR3 to boost antitumor immunity.

Inducing tertiary lymphoid structure (TLS) formation can fuel antitumor immunity. It is necessary to create mouse models containing TLS to explore strategies of TLS formation. Oncolytic herpes simplex virus-1 (oHSV) exhibited intense effects in preclinical and clinical trials. However, the role of oHSV in TLS formation remains to be elucidated. Here, we observed the presence of TLS in 4MOSC1 and MC38 subcutaneous tumour models. Interestingly, oHSV evoked TLS formation, and increased infiltration of B cells and stem-like TCF1+CD8+ T cells proliferation. Mechanistically, oHSV increased the expression of TLS-related chemokines, along with upregulated CXCL10/CXCR3 to facilitate TLS formation. Notably, CXCL10 and CXCR3 were favourable prognostic factors for cancer patients, and closely related with immune cells infiltration. Inhibiting CXCL10/CXCR3 reduced TCF1+CD8+ T cells and granzyme B expression, and impaired oHSV-mediated TLS formation. Furthermore, oHSV-mediated TLS formation revealed superior response and survival rate when combined with αPD-1 treatment. Collectively, these findings indicate that oHSV recruits stem-like TCF1+CD8+ T cells through CXCL10/CXCR3 pathway to propagate TLS formation, and warrants future antitumor immunity development.

Spatial analysis of the prevalence of abdominal obesity in middle-aged and older adult people in China: exploring the relationship with meteorological factors based on gender differences.

Background: In recent years, the incidence of abdominal obesity among the middle-aged and older adult population in China has significantly increased. However, the gender disparities in the spatial distribution of abdominal obesity incidence and its relationship with meteorological factors among this demographic in China remain unclear. This gap in knowledge highlights the need for further research to understand these dynamics and inform targeted public health strategies. Methods: This study utilized data from the 2015 China Health and Retirement Longitudinal Study (CHARLS) to analyze the incidence of abdominal obesity among the middle-aged and older adult population in China. Additionally, meteorological data were collected from the National Meteorological Information Center. Using Moran's I index and Getis-Ord Gi* statistical methods, the spatial distribution characteristics of abdominal obesity incidence were examined. The influence of various meteorological factors on the incidence of abdominal obesity in middle-aged and older adult males and females was investigated using the q statistic from the Geodetector method. Furthermore, Multi-Scale Geographically Weighted Regression (MGWR) analysis was employed to explore the impact of meteorological factors on the spatial heterogeneity of abdominal obesity incidence from a gender perspective. Results: The spatial distribution of abdominal obesity among middle-aged and older adult individuals in China exhibits a decreasing trend from northwest to southeast, with notable spatial autocorrelation. Hotspots are concentrated in North and Northeast China, while cold spots are observed in Southwest China. Gender differences have minimal impact on spatial clustering characteristics. Meteorological factors, including temperature, sunlight, precipitation, wind speed, humidity, and atmospheric pressure, influence incidence rates. Notably, temperature and sunlight exert a greater impact on females, while wind speed has a reduced effect. Interactions among various meteorological factors generally demonstrate bivariate enhancement without significant gender disparities. However, gender disparities are evident in the influence of specific meteorological variables such as annual maximum, average, and minimum temperatures, as well as sunlight duration and precipitation, on the spatial heterogeneity of abdominal obesity incidence. Conclusion: Meteorological factors show a significant association with abdominal obesity prevalence in middle-aged and older adults, with temperature factors playing a prominent role. However, this relationship is influenced by gender differences and spatial heterogeneity. These findings suggest that effective public health policies should be not only gender-sensitive but also locally adapted.

Computed Tomography Imaging Guided Microenvironment-Responsive Ir@WO3-x Dual-Catalytic Nanoreactor for Selective Radiosensitization.

Radiotherapy (RT) is often administered, either alone or in combination with other therapies, for most malignancies. However, the degree of tumor oxygenation, damage to adjacent healthy tissues, and inaccurate guidance remain issues that result in discontinuation or failure of RT. Here, a multifunctional therapeutic platform based on Ir@WO3-x is developed which simultaneously addresses these critical issues above for precision radiosensitization. Ir@WO3-x nanoreactors exhibit strong absorption of X-ray, acting as radiosensitizers. Moreover, ultrasmall Ir enzyme-mimic nanocrystals (NCs) are decorated onto the surface of the nanoreactor, where NCs have catalyst-like activity and are sensitive to H2O2 in the tumor microenvironment (TME) under near infrared-II (NIR-II) light stimulation. They efficiently catalyze the conversion of H2O2 to O2, thereby ameliorating hypoxia, inhibiting the expression of HIF-1α, and enhancing RT-induced DNA damage in cancerous tissue, further improving the efficiency of RT. Additionally, in response to high H2O2 levels in TME, the Ir@WO3-x nanoreactor also exerts peroxidase-like activity, boosting exogenous ROS, which increases oxidative damage and enhances ROS-dependent death signaling. Furthermore, Ir@WO3-x can serve as a high-quality computed tomography contrast agent due to its high X-ray attenuation coefficient and generation of pronounced tumor-tissue contrast. This report highlights the potential of advanced health materials to enhance precision therapeutic modalities.

Choroidal vascular changes in early-stage myopic maculopathy from deep learning choroidal analysis: a hospital-based SS-OCT study.

BACKGROUND: The objective of this study is to illustrate the changes in the choroidal vasculature in individuals with diffuse chorioretinal atrophy (DCA, early-stage myopic maculopathy) and investigate the association between them. METHODS: This study included 1418 highly myopic eyes from 720 participants aged 18 - 60 years from the Wenzhou High Myopia Cohort Study. These participants underwent comprehensive ophthalmic assessments. Myopic maculopathy classification followed the Meta-PM system, with pathological myopia defined as myopic maculopathy of DCA or severer. Eyes with myopic maculopathy categorized as no macular lesions (C0), tessellated fundus (C1), and DCA (C2) were enrolled in the analysis. Choroidal images were obtained from swept-source optical coherence tomography (SS-OCT), and the images were processed with a deep learning-based automatic segmentation algorithm and the Niblack auto-local threshold algorithm. RESULTS: DCA was detected in 247 eyes (17.4%). In comparison to eyes with C0, those with C2 exhibited significant reductions in choroidal thickness (ChT), luminal area (LA), and stromal area (SA) across all evaluated regions (all P < 0.001). An increase in choroidal vascular index (CVI) was observed in all regions, except for the nasal perifoveal (N2) and inferior perifoveal (I2) regions (all P < 0.01). Multivariable logistic regression analysis revealed a negative association between the presence of DCA and increases in choroidal LA and SA (odds ratio ≤ 0.099, P < 0.001). Multivariable linear regression analysis showed that the mean deviation of the visual field test was positively associated with LA and SA at the vertical meridian (B = 1.512, P < 0.001 for LA; B = 1.956, P < 0.001 for SA). Furthermore, the receiver operating characteristic curve analyses showed the optimal ChT to diagnose pathological myopia was 82.4 µm in the N2 region, the LA was 0.076 mm2 and the SA was 0.049 mm2, with area under the curves of 0.916, 0.908, and 0.895, respectively. CONCLUSIONS: The results of this study indicated that both the presence of DCA and visual function impairment were associated with reductions in choroidal perfusion and stromal components. Moreover, we established threshold values for choroidal parameters in diagnosing pathological myopia, offering valuable references for clinical diagnosis and management.

Influences of noise reduction on speech intelligibility, listening effort, and sound quality among adults with severe to profound hearing loss.

Introduction: Noise reduction (NR) algorithms have been integrated into modern digital hearing aids to reduce noise annoyance and enhance speech intelligibility. This study aimed to evaluate the influences of a novel hearing aid NR algorithm on individuals with severe-to-profound hearing loss. Methods: Twenty-five participants with severe-to-profound bilateral sensorineural hearing loss underwent three tests (speech intelligibility, listening effort, and subjective sound quality in noise) to investigate the influences of NR. All three tests were performed under three NR strength levels (Off, Moderate, and Strong) for both speech in noise program (SpiN) and speech in loud noise program (SpiLN), comprising six different hearing aid conditions. Results: NR activation significantly reduced listening effort. Subjective sound quality assessments also exhibited benefits of activated NR in terms of noise suppression, listening comfort, satisfaction, and speech clarity. Discussion: Individuals with severe-to-profound hearing loss still experienced advantages from NR technology in both listening effort measure and subjective sound quality assessments. Importantly, these benefits did not adversely affect speech intelligibility.

Dopaminylation of endothelial TPI1 suppresses ferroptotic angiocrine signals to promote lung regeneration over fibrosis.

Lungs can undergo facultative regeneration, but handicapped regeneration often leads to fibrosis. How microenvironmental cues coordinate lung regeneration via modulating cell death remains unknown. Here, we reveal that the neurotransmitter dopamine modifies the endothelial niche to suppress ferroptosis, promoting lung regeneration over fibrosis. A chemoproteomic approach shows that dopamine blocks ferroptosis in endothelial cells (ECs) via dopaminylating triosephosphate isomerase 1 (TPI1). Suppressing TPI1 dopaminylation in ECs triggers ferroptotic angiocrine signaling to aberrantly activate fibroblasts, leading to a transition from lung regeneration to fibrosis. Mechanistically, dopaminylation of glutamine (Q) 65 residue in TPI1 directionally enhances TPI1's activity to convert dihydroxyacetone phosphate (DHAP) to glyceraldehyde 3-phosphate (GAP), directing ether phospholipid synthesis to glucose metabolism in regenerating lung ECs. This metabolic shift attenuates lipid peroxidation and blocks ferroptosis. Restoring TPI1 Q65 dopaminylation in an injured endothelial niche overturns ferroptosis to normalize pro-regenerative angiocrine function and alleviate lung fibrosis. Overall, dopaminylation of TPI1 balances lipid/glucose metabolism and suppresses pro-fibrotic ferroptosis in regenerating lungs.

[Combination of acupuncture therapy and kinesiotherapy: an example of pain rehabilitation].

The effect mechanism and the characteristics of clinical application of the combination of acupuncture therapy and kinesiotherapy are explored for pain rehabilitation. Analgesia of acupuncture therapy and kinesiotherapy is characterized by multiple targets and dimensions. The paper summarizes the effect mechanisms of these two therapies and their synergistic action and investigates the current situation and clinical characteristics of their combination in treatment of musculoskeletal pain, visceral pain and postoperative pain so that the references can be provided for the selection of pain rehabilitation programs.

Study on the Tribological Properties of Multilayer Concentric Hexagonal Laser Texturing on Rubber Surfaces of Screw Pumps.

Given the friction and drag reduction effects observed in various biological hexagonal structures in nature, a new design was implemented on the rubber surface of the stator of a submersible screw pump. This design featured a multilayer concentric hexagonal groove structure. Furthermore, a composite multilayer hexagonal structure integrating grooves and pits was also developed and applied. This study investigated the influence of groove layer number, groove depth, pit depth, and multilayer hexagonal groove texture arrangement on the rubber surface flow characteristics. Additionally, the pressure field state, the degree of influence on the oil film-bearing capacity, and the biomimetic and hydrodynamic lubrication theories were tested using the finite element analysis method. Tribological experiments were conducted on nanosecond laser-processed rubber textures under simulated liquid lubrication conditions, reflecting actual shale oil well experiments. These experiments aimed to investigate the influence of multilayer hexagonal shape parameters on the tribological characteristics of the stator-rotor friction pair of a submersible screw pump. The results indicated that with a constant overall size, a multilayer hexagonal structure with ~0.1 mm groove depth enhanced the oil film-bearing capacity, providing significant friction and drag reduction. For composite textures, a deeper pit depth within the study area enhanced the oil film-bearing capacity. Furthermore, a gradient arrangement of groove textures featuring wider outer grooves and shallower depth exhibited superior performance in terms of bearing capacity.

Ochratoxin A-induced DNA damage triggers G2 phase arrest via hMLH1-p53-p21 signaling pathway in human gastric epithelium immortalized cells in vitro.

Ochratoxin A (OTA), as one of the most important and harmful mycotoxins, is classed as possible human carcinogen (group 2B). As we all know, DNA damage may cause genomic instability, cell cycle disorder, activation of DNA damage pathway, and stimulation of DNA repair system. To explore the roles of DNA damage repair protein (hMLH1) on OTA-induced G2 arrest, the DNA damage, chromosome aberration, cell cycle distribution and p53-p21 signaling pathway were evaluatd after different time OTA exposure (6, 12, 24, 48h) in immortalized human gastric epithelial cells (GES-1). Our results demonstrated that OTA exposure could trigger genomic instability, DNA damage and G2 phase arrest of GES-1 cells. At the same time, OTA treatment could increase the expression of hMLH1, and induce phosphorylation of the p53 protein, as well as p21, in response to DNA damage. Finally, inhibition of hMLH1 by siRNA effectively prevented the activation of p53-p21 signaling pathway and rescued the G2 arrest elicited by OTA. This study demonstrated that hMLH1-p53-p21 signaling pathway played an important role in DNA damage and G2 cell cycle arrest the mediated by OTA in GES-1 cells.

SEC16A Variants Predispose to Chronic Pancreatitis by Impairing ER-to-Golgi Transport and Inducing ER Stress.

Chronic pancreatitis (CP) is a complex disease with genetic and environmental factors at play. Through trio exome sequencing, a de novo SEC16A frameshift variant in a Chinese teenage CP patient is identified. Subsequent targeted next-generation sequencing of the SEC16A gene in 1,061 Chinese CP patients and 1,196 controls reveals a higher allele frequency of rare nonsynonymous SEC16A variants in patients (4.90% vs 2.93%; odds ratio [OR], 1.71; 95% confidence interval [CI], 1.26-2.33). Similar enrichments are noted in a French cohort (OR, 2.74; 95% CI, 1.67-4.50) and in a biobank meta-analysis (OR, 1.16; 95% CI, 1.04-1.31). Notably, Chinese CP patients with SEC16A variants exhibit a median onset age 5 years earlier than those without (40.0 vs 45.0; p = 0.012). Functional studies using three CRISPR/Cas9-edited HEK293T cell lines show that loss-of-function SEC16A variants disrupt coat protein complex II (COPII) formation, impede secretory protein vesicles trafficking, and induce endoplasmic reticulum (ER) stress due to protein overload. Sec16a+/- mice, which demonstrate impaired zymogen secretion and exacerbated ER stress compared to Sec16a+/+, are further generated. In cerulein-stimulated pancreatitis models, Sec16a+/- mice display heightened pancreatic inflammation and fibrosis compared to wild-type mice. These findings implicate a novel pathogenic mechanism predisposing to CP.

Promoting the healing of infected diabetic wound by nanozyme-containing hydrogel with anti-bacterial inflammation suppressing, ROS-scavenging and oxygen-generating properties.

Bacterial infections already pose a significant threat to skin wounds, especially in diabetic patients who have difficulty healing wounds. However, wound or bacterial infections are known to produce excess reactive oxygen species (ROS), and hypoxia may further hinder wound healing and the development of chronic wounds. In this study, a multifunctional hydrogel for ROS scavenging and bacterial inhibition was developed by cross-linking polyvinyl alcohol (PVA) and sodium alginate (SA) with graphene oxide (GO) loaded with silver-platinum hybrid nanoparticles (GO@Ag-Pt). The PVA/SA hydrogel loaded with GO@Ag-Pt exhibited the ability to scavenge different types of ROS, generate O2, and kill a broad spectrum of bacteria in vitro. The silver-platinum hybrid nanoparticles significantly increased the antibacterial ability against Escherichia coli and Staphylococcus aureus compared with silver nanoparticles (AgNps). GO@Ag-Pt loaded hydrogel was effective in treating infections caused by S.aureus, thereby significantly promoting wound healing during the inflammatory phase. Hydrogel therapy significantly reduced the level of ROS and alleviated inflammation levels. Notably, our ROS-scavenging, antibacterial hydrogels can be used to effectively treat various types of wounds, including difficult-to-heal diabetic wounds with bacterial infections. Thus, this study proposes an effective strategy for various chronic wound healing based on ROS clearance and bacteriostatic hydrogels.