Glutathionylation of a glycolytic enzyme promotes cell death and vigor loss during aging of elm seeds.

Seed deterioration during storage is a major problem in agricultural and forestry production and for germplasm conservation. Our previous studies have shown that a mitochondrial outer membrane protein VOLTAGE-DEPENDENT ANION CHANNEL (VDAC) is involved in programmed cell death (PCD)-like viability loss during the controlled deterioration treatment (CDT) of elm (Ulmus pumila L.) seeds, but its underlying mechanism remains unclear. In this study, we demonstrate that the oxidative modification of GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE (GAPDH) is functioned in the gate regulation of VDAC during the CDT of elm seeds. Through biochemical and cytological methods and observations of transgenic material [Arabidopsis (Arabidopsis thaliana), Nicotiana benthamiana, and yeast (Saccharomyces cerevisiae)], we demonstrate that cysteine S-glutathionylated UpGAPDH1 interacts with UpVDAC3 during seed aging, which leads to a mitochondrial permeability transition and aggravation of cell death, as indicated by the leakage of the mitochondrial pro-apoptotic factor cytochrome c and the emergence of apoptotic nucleus. Physiological assays and inductively coupled plasma mass spectrometry (ICP-MS) analysis revealed that GAPDH glutathionylation is mediated by increased glutathione, which might be caused by increases in the concentrations of free metals, especially Zn. Introduction of the Zn-specific chelator TPEN [(N, N, N', N'-Tetrakis (2-pyridylmethyl)ethylenediamine)] significantly delayed seed aging. We conclude that glutathionylated UpGAPDH1 interacts with UpVDAC3 and serves as a pro-apoptotic protein for VDAC-gating regulation and cell death initiation during seed aging.

Structural Equation Modelling to Identify Psychometric Determinants of Medication Adherence in a Survey of Kidney Dialysis Patients.

Purpose: Medication non-adherence in dialysis patients is associated with increased mortality and higher healthcare costs. We assessed whether medication adherence is influenced by specific psychometric constructs measuring beliefs about the necessity for medication and concerns about them. We also tested whether medication knowledge, health literacy, and illness perceptions influenced this relationship. Patients and Methods: This study is based on data from a cross-sectional in-person questionnaire, administered to a random sample of all adult dialysis patients at a teaching hospital. The main outcome was self-assessed medication adherence (8-Item Morisky Medication Adherence Scale). The predictors were: concerns about medications and necessity for medication (Beliefs About Medication Questionnaire); health literacy; medication knowledge (Medication Knowledge Evaluation Tool); cognitive, emotional, and comprehensibility Illness perceptions (Brief Illness Perception Questionnaire). Path analysis was performed using structural equations in both covariance and variance-based models. Results: Necessity for medication increased (standardized path coefficient [ß] 0.30 [95% CI 0.05, 0.54]) and concerns about medication decreased (standardized ß -0.33 [-0.57, -0.09]) medication adherence, explaining most of the variance in outcome (r2=0.95). Medication knowledge and cognitive illness perceptions had no effects on medication adherence, either directly or indirectly. Higher health literacy, greater illness comprehension, and a more positive emotional view of their illness had medium-to-large sized effects in increasing medication adherence. These were indirect rather and direct effects mediated by decreases in concerns about medications (standardized ß respectively -0.40 [-0.63,-0.16], -0.60 [-0.85, -0.34], -0.33 [-0.52, -0.13]). Conclusion: Interventions that reduce patients' concerns about their medications are likely to improve adherence, rather than interventions that increase patients' perceived necessity for medication. Improving patients' general health literacy and facilitating a better understanding and more positive perception of the illness can probably achieve this. Our study is potentially limited by a lack of generalizability outside of the population and setting in which it was conducted.

Risk effects of meteorological factors on human brucellosis in Jilin province, China, 2005-2019.

Background: The impact of climate on zoonotic infectious diseases (or can be referred to as climate-sensitive zoonotic diseases) is confirmed. Yet, research on the association between brucellosis and climate is limited. We aim to understand the impact of meteorological factors on the risk of brucellosis, especially in northeastern China. Methods: Monthly incidence data for brucellosis from 2005 to 2019 in Jilin province was obtained from the China Information System for Disease Control and Prevention (CDC). Monthly meteorological data (average temperature (°C), wind velocity (m/s), relative humidity (%), sunshine hours (h), air pressure (hPa), and rainfall (mm)) in Jilin province, China, from 2005 to 2019 were collected from the China Meteorological Information Center (http://data.cma.cn/). The Spearman's correlation was used to choose among the several meteorological variables. A distributed lag non-linear model (DLNM) was used to estimate the lag and non-linearity effect of meteorological factors on the risk of brucellosis. Results: A total of 24,921 cases of human brucellosis were reported in Jilin province from 2005 to 2019, with the peak epidemic period from April to June. Low temperature and low sunshine hours were protective factors for the brucellosis, where the minimum RR values were 0.50 (95 % CI = 0.31-0.82) for -13.7 °C with 1 month lag and 0.61 (95 % CI = 0.41-0.91) for 110.5h with 2 months lag, respectively. High temperature, high sunshine hours, and low wind velocity were risk factors for brucellosis. The maximum RR values were 2.91 (95 % CI = 1.43-5.92, lag = 1, 25.7 °C), 1.85 (95 % CI = 1.23-2.80, lag = 2, 332.6h), and 1.68 (95 % CI = 1.25-2.26, lag = 2, 1.4 m/s). The trends in the impact of extreme temperature and extreme sunshine hours on the transmission of brucellosis were generally consistent. Conclusion: High temperature, high sunshine hours, and low wind velocity are more conducive to the transmission of brucellosis with an obvious lag effect. The results will deepen the understanding of the relationship between climate and brucellosis and provide a reference for formulating relevant public health policies.

FoxO3 regulates mouse bone mesenchymal stem cell fate and bone-fat balance during skeletal aging.

Age-related osteoporosis is characterized by an imbalance between osteogenic and adipogenic differentiation in bone mesenchymal stem cells (BMSCs). Forkhead box O 3 (FoxO3) transcription factors is involved in lifespan and cell differentiation. In this study, we explore whether FoxO3 regulates age-related bone loss and marrow fat accumulation. The expression levels of FoxO3 in BMSCs during aging were detected in vivo and in vitro. To explore the role of FoxO3 in osteogenic and adipogenic differentiation, primary BMSCs were isolated from young and aged mice. FoxO3 expression was modulated by adenoviral vector transfection. The role of FoxO3 in bone-fat balance was evaluated by alizarin red S staining, oil red O staining, quantitative reverse transcription-PCR (qRT-PCR), western blot (WB) and histological analysis. Age-related bone loss and fat deposit are associated with downregulation of FoxO3. Overexpression of FoxO3 alleviated age-related bone loss and marrow fat accumulation in aged mice. Mechanistically, FoxO3 reduced adipogenesis and enhanced osteogenesis of BMSCs via downregulation of PPAR-γ and Notch signaling respectively. In conclusion, FoxO3 is an essential factor controlling the fate of BMSCs, and is a potential target for prevention of age-related osteoporosis.

Synergistic detoxification efficiency and mechanism of triclocarban degradation by a bacterial consortium in the liver-gut-microbiota axis of zebrafish (Danio rerio).

Triclocarban (TCC), an emerging organic contaminant, poses a potential threat to human health with long-term exposure. Here, Rhodococcus rhodochrous BX2 and Pseudomonas sp. LY-1 were utilized to degrade TCC at environmental related concentrations for enhancing TCC biodegradation and investigating whether the toxicity of intermediate metabolites is lower than that of the parent compound. The results demonstrated that the bacterial consortium could degrade TCC by 82.0% within 7 days. The calculated 96 h LC50 for TCC, as well as its main degradation product 3,4-Dichloroaniline (DCA) were 0.134 mg/L and 1.318 mg/L respectively. Biodegradation also alleviated histopathological lesions induced by TCC in zebrafish liver and gut tissues. Liver transcriptome analysis revealed that biodegradation weakened differential expression of genes involved in disrupted immune regulation and lipid metabolism caused by TCC, verified through RT-qPCR analysis and measurement of related enzyme activities and protein contents. 16 S rRNA sequencing indicated that exposure to TCC led to gut microbial dysbiosis, which was efficiently improved through TCC biodegradation, resulting in decreased relative abundances of major pathogens. Overall, this study evaluated potential environmental risks associated with biodegradation of TCC and explored possible biodetoxification mechanisms, providing a theoretical foundation for efficient and harmless bioremediation of environmental pollutants.

Lei's formula attenuates osteoarthritis mediated by suppression of chondrocyte senescence via the mTOR axis: in vitro and in vivo experiments.

Lei's formula (LSF), a traditional Chinese herbal remedy, is recognized for its remarkable clinical effectiveness in treating osteoarthritis (OA). Despite its therapeutic potential, the exact molecular mechanisms underlying LSF's action in OA have remained enigmatic. Existing research has shed light on the role of the mTOR signaling pathway in promoting chondrocyte senescence, a central factor in OA-related cartilage degeneration. Consequently, targeting mTOR to mitigate chondrocyte senescence presents a promising avenue for OA treatment. The primary objective of this study is to establish LSF's chondroprotective potential and confirm its anti-osteoarthritic efficacy through mTOR inhibition. In vivo assessments using an OA mouse model reveal substantial articular cartilage degeneration. However, LSF serves as an effective guardian of articular cartilage, evidenced by reduced subchondral osteosclerosis, increased cartilage thickness, improved surface smoothness, decreased OARSI scores, elevated expression of cartilage anabolic markers (Col2 and Aggrecan), reduced expression of catabolic markers (Adamts5 and MMP13), increased expression of the chondrocyte hypertrophy marker (Col10), and decreased expression of chondrocyte senescence markers (P16 and P21). In vitro findings demonstrate that LSF shields chondrocytes from H2O2-induced apoptosis, inhibits senescence, enhances chondrocyte differentiation, promotes the synthesis of type II collagen and proteoglycans, and reduces cartilage degradation. Mechanistically, LSF suppresses chondrocyte senescence through the mTOR axis, orchestrating the equilibrium between chondrocyte anabolism and catabolism, ultimately leading to reduced apoptosis and decelerated OA cartilage degradation. LSF holds significant promise as a therapeutic approach for OA treatment, offering new insights into potential treatments for this prevalent age-related condition.

Exogenous hydrogen sulphide promotes plant flowering through the Arabidopsis splicing factor AtU2AF65a.

Alternative splicing (AS) is an important regulatory mode at the post-transcriptional level, through which many flowering genes regulate floral transition by producing multiple transcripts, and splicing factors have essential roles in this process. Hydrogen sulphide (H2S) is a newly found gasotransmitter that has critical physiological roles in plants, and one of its potential modes of action is via persulfidation of target proteins at specific cysteine sites. Previously, it has been shown that both the splicing factor AtU2AF65a and H2S are involved in the regulation of plant flowering. This study found that, in Arabidopsis, the promoting effect of H2S on flowering was abolished in atu2af65a-4 mutants. Transcriptome analyses showed that when AtU2AF65a contained mutations, the regulatory function of H2S during the AS of many flowering genes (including SPA1, LUH, LUG and MAF3) was inhibited. The persulfidation assay showed that AtU2AF65a can be persulfidated by H2S, and the RNA immunoprecipitation data indicated that H2S could alter the binding affinity of AtU2AF65a to the precursor messenger RNA of the above-mentioned flowering genes. Overall, our results suggest that H2S may regulate the AS of flowering-related genes through persulfidation of splicing factor AtU2AF65a and thus lead to early flowering in plants.

Role of TGF-ß3 in modulating inflammatory responses and wound healing processes in ischemic ulcers in atherosclerotic patients.

Ischemic ulcers pose a multifaceted clinical dilemma for patients with atherosclerosis, frequently compounded by suboptimal wound healing mechanisms. The dual function of Transforming Growth Factor Beta 3 (TGF-ß3) in ischemic ulcer healing is not fully comprehended, despite its involvement in modulating inflammatory responses and tissue regeneration. The main aim of this investigation was to clarify the functions and mechanisms by which TGF-ß3 regulates inflammatory responses and promotes wound healing in patients with ischemic ulcers who have atherosclerosis. Between August 2022 and November 2023, this cross-sectional investigation was conducted on 428 patients diagnosed with atherosclerotic ischemic ulcers in Haikou, China. The expression and function of TGF-ß3 were examined throughout the different stages of wound healing, including inflammation, proliferation and remodelling. In addition to documenting patient demographics and ulcer characteristics, an analysis was conducted on biopsy samples to determine the expression of TGF-ß3, pro-inflammatory and anti-inflammatory markers. A subset of patients were administered topical TGF-ß3 in order to evaluate its therapeutic effects. The expression pattern of TGF-ß3 was found to be stage-dependent and significant, exhibiting increased levels during the phase of inflammation and reduced activity in subsequent phases. TGF-ß3 levels were found to be greater in ulcers that were larger and deeper, especially in inflammatory phase. TGF-ß3 applied topically induced discernible enhancement in ulcer healing parameters, such as reduction in ulcer depth and size. The therapeutic significance of TGF-ß3 was emphasised due to its twofold function of regulating the inflammatory environment and facilitating the regeneration of damaged tissues. Ischemic ulcer lesion healing is significantly influenced by TGF-ß3, which functions as an anti-inflammatory and pro-inflammatory mediator. Its correlation with ulcer characteristics and stages of healing suggests that it may have utility as a targeted therapeutic agent.

A half jaw panoramic stitching method of intraoral endoscopy images based on dental arch arrangement.

To address the challenges of repetitive and low-texture features in intraoral endoscopic images, a novel methodology for stitching panoramic half jaw images of the oral cavity is proposed. Initially, an enhanced self-attention mechanism guided by Time-Weighting concepts is employed to augment the clustering potential of feature points, thereby increasing the number of matched features. Subsequently, a combination of the Sinkhorn algorithm and Random Sample Consensus (RANSAC) is utilized to maximize the count of matched feature pairs, accurately remove outliers and minimize error. Last, to address the unique spatial alignment among intraoral endoscopic images, a wavelet transform and weighted fusion algorithm based on dental arch arrangement in intraoral endoscopic images have been developed, specifically for use in the fusion stage of intraoral endoscopic images. This enables the local oral images to be precisely positioned along the dental arch, and seamless stitching is achieved through wavelet transformation and a gradual weighted fusion technique. Experimental results demonstrate that this method yields promising outcomes in panoramic stitching tasks for intraoral endoscopic images, achieving a matching accuracy of 84.6% and a recall rate of 78.4% in a dataset with an average overlap of 35%. A novel solution for panoramic stitching of intraoral endoscopic images is provided by this method.

Polyoxometalate-Structured Materials: Molecular Fundamentals and Electrocatalytic Roles in Energy Conversion.

Polyoxometalates (POMs), a kind of molecular metal oxide cluster with unique physical-chemical properties, have made essential contributions to creating efficient and robust electrocatalysts in renewable energy systems. Due to the fundamental advantages of POMs, such as the diversity of molecular structures and large numbers of redox active sites, numerous efforts have been devoted to extending their application areas. Up to now, various strategies of assembling POM molecules into superstructures, supporting POMs on heterogeneous substrates, and POMs-derived metal compounds have been developed for synthesizing electrocatalysts. From a multidisciplinary perspective, the latest advances in creating POM-structured materials with a unique focus on their molecular fundamentals, electrocatalytic roles, and the recent breakthroughs of POMs and POM-derived electrocatalysts, are systematically summarized. Notably, this paper focuses on exposing the current states, essences, and mechanisms of how POM-structured materials influence their electrocatalytic activities and discloses the critical requirements for future developments. The future challenges, objectives, comparisons, and perspectives for creating POM-structured materials are also systematically discussed. It is anticipated that this review will offer a substantial impact on stimulating interdisciplinary efforts for the prosperities and widespread utilizations of POM-structured materials in electrocatalysis.

Multiomics analysis reveals that microbiota regulate fat and muscle synthesis in chickens.

Intestinal microbiota regulates the host metabolism, including fat metabolism and muscle development in mammals; however, studies on the interactions between the gut microbiome and in chickens with respect to fat metabolism and muscle development are still rare. We established a germ-free (GF) chicken model to determine the transcriptomes and metabolomes of GF and specific-pathogen-free (SPF) chickens. Transcriptome analysis showed 1,282 differentially expressed genes (DEGs) in GF and SPF chickens. The expression levels of some genes related to muscle formation were very high in SPF chickens but low in GF chickens, suggesting that GF chickens had poorer muscle development ability. In contrast, the expression levels of some fat synthesis-related genes were very low in SPF chickens but high in GF chickens, suggesting that GF chickens had a more potent fat-synthesizing ability. Metabolome analysis revealed 62 differentially expressed metabolites (DEMs) in GF and SPF chickens, of which 35 were upregulated and 27 were downregulated. Furthermore, the Pearson correlation coefficient (PCC) was calculated, and an interaction network was constructed to visualize the crosstalk between the genes, metabolites, and gut microbiota in GF and SPF chickens. The top 10 gut microbiota were positively correlated with lipid metabolism including13(S)-HpODE and 9(S)-HpOTrE, and genes related to muscle development, while were negatively correlated with genes related to fat synthesis. In conclusion, this study indicated that chicken intestinal microbiota regulate host metabolism, inhibit fat synthesis, and may promote muscle development.

Clinical study of camrelizumab combined with docetaxel and carboplatin as a neoadjuvant treatment for locally advanced oesophageal squamous cell carcinoma.

Herein, we aimed to evaluate the efficacy and safety of camrelizumab combined with docetaxel and carboplatin as a neoadjuvant treatment for locally advanced oesophageal squamous cell carcinoma (OSCC). Fifty-one patients with OSCC, treated from July 2020 to October 2022, were analyzed. Of them, 41 patients underwent surgery 4-8 weeks after undergoing two cycles of camrelizumab (200 mg IV Q3W) combined with docetaxel (75 mg/m2 IV Q3W) and carboplatin (area under the curve = 5-6 IV Q3W). The primary endpoint was the pathological complete response rate. All 51 patients (100%) experienced treatment-related grades 1-2 adverse events, and 2 patients (3.9%) experienced grade 4 events (including elevated alanine transaminase/aspartate transferase levels and Guillain-Barre syndrome). Fifty patients were evaluated for the treatment efficacy. Of them, 13 achieved complete response, and the objective response rate was 74%. Only 41 patients underwent surgical treatment. The pathological complete response rate was 17.1%, the major pathological response rate was 63.4%, and the R0 resection rate was 100%. Approximately 22% of the patients had tumor regression grades 0. Eight patients (19.5%) developed surgery-related complications. The median follow-up time was 18 months (range: 3-29 months). Four patients experienced disease progression, while four died. The median disease-free survival and overall survival were not reached. Camrelizumab combined with docetaxel and carboplatin is an effective and safe neoadjuvant treatment for locally advanced OSCC. This regimen may afford a potential strategy to treat patients with locally advanced OSCC.

Investigating the Impact of Humic Acid on Copper Accumulation in Sinonovacula constricta Using a Toxicokinetic-Toxicodynamic Model.

In aquatic ecosystems, the interaction between heavy metals and dissolved organic carbon (DOC) plays a pivotal role in modifying the bioavailability of these metals. This study, employing a toxicokinetic-toxicodynamic model, delves into the interactive effects of humic acid (HA), a significant component of DOC, on the bioaccumulation and toxicity of copper (Cu) in the estuarine economic bivalve Sinonovacula constricta. Utilizing the stable isotope 65Cu as a tracer, we evaluated Cu uptake in S. constricta under varied DOC concentrations in a controlled laboratory setting. Our findings reveal that at DOC concentrations below 3.05 mg L-1, the bioavailability of Cu is reduced due to shifts in the speciation distribution of Cu, resulting in decreased bioaccumulation within S. constricta. Conversely, at DOC levels exceeding 3.05 mg L-1, the formation of colloidal Cu-HA complexes allows its entry into the bivalves' digestive system. Moreover, toxicity assays demonstrate an increase in S. constricta survival rates with higher DOC concentrations, suggesting a protective effect of DOC against Cu toxicity. The integration of accumulation and toxicity data infers that Cu-HA complexes, when ingested via the digestive tract, exhibit lower toxicity compared to Cu directly assimilated from the water phase. These findings emphasize the need to consider environmental DOC levels in assessing Cu pollution risks and provide insights for managing heavy metal toxicity in estuarine aquaculture.

Two-dimensional graphene+ as an anode material for calcium-ion batteries with ultra-high capacity: a first-principles study.

Multivalent-ion batteries have garnered significant attention due to their high energy density, low cost, and superior safety. Calcium-ion batteries (CIBs) are regarded as the next-generation energy storage systems for their abundant natural resources and bivalent characteristics. However, the absence of high-performance anode materials poses a significant obstacle to the progress of battery technology. Two-dimensional (2D) Dirac materials have excellent conductivity and abundant active sites, rendering them promising candidates as anode materials. A novel 2D Dirac material known as "graphene+" has been theoretically reported, exhibiting prominent properties including good stability, exceptional ductility, and remarkable electronic conductivity. By using first-principles calculations, we systematically investigate the performance of graphene+ as an anode material for CIBs. Graphene+ exhibits an ultra-high theoretical capacity (1487.7 mA h g-1), a small diffusion barrier (0.21 eV), and a low average open-circuit voltage (0.51 V). Furthermore, we investigate the impact of the electrolyte solvation on the performance of Ca-ion adsorption and migration. Upon contact with electrolyte solvents, graphene+ exhibits strong adsorption strength and rapid migration of Ca-ions on its surface. These results demonstrate the promising potential of graphene+ as a high-performance anode material for CIBs.

Long-term maintenance of high yield and soil fertility with integrated soil-crop system management on the Loess Plateau.

Ridge-furrow with full film mulching has been widely applied to increase crop yield and water productivity on the Loess Plateau, but it may stimulate carbon (C) mineralization. How to integrate other technological benefits based on this technology for long-term maintenance of high yield and soil fertility is a pressing issue. With the local farmers' practice (FP) as a control, three integrated soil-crop system management (ISSM) practices integrating fertilizer rates, fertilizer types and planting densities (ISSM-N1, ISSM-N2 and ISSM-MN) were established to improve maize yield and soil quality. Compared with the FP, the maize yield increased by 13.34%, 21.83% and 30.24%, and the soil quality index (SQI) increased by 9.66%, 14.91% and 38.38% for ISSM-N1, ISSM-N2 and ISSM-MN, respectively. However, ISSM-N1 did not significantly increase yield, and ISSM-N2 increased residual soil nitrate and decreased nitrogen (N) partial factor productivity significantly. Compared to the FP, ISSM practices increased soil organic carbon (SOC), labile organic C fractions (LOCFs) and potassium permanganate organic C fractions in the topsoil to varying degrees, but only ISSM-MN reached significant levels for most C fractions. The sensitivity index indicated very easily oxidizable C (24.6%), easily oxidizable C (24.7%), hot-water extractable C (30.8%), labile organic C (24.7%) and particulate organic C (57.3%) were more sensitive than SOC (22.7%). ISSM-MN sequestered significantly higher C than the other treatments. The results of the relative importance analysis and the structural equation model indicated that LOCFs were the direct contributors to yield, while recalcitrant C (CO) was the indirect contributor, revealing the underlying mechanism that CO decomposed to replenish LOCFs and the total N pool with the water soluble C pool as the transit station. Overall, ISSM-MN is the most promising strategy to improve crop yield and soil fertility in the long term on the Loess Plateau.

Spiky Artificial Peroxidases with V-O-Fe Pair Sites for Combating Antibiotic-Resistant Pathogens.

With the sharp rise of antibiotic-resistant pathogens worldwide, it is of enormous importance to create new strategies for combating pathogenic bacteria. Here, we create an iron oxide-based spiky artificial peroxidase (POD) with V-O-Fe pair sites (V-Fe2 O3 ) for combating methicillin-resistant Staphylococcus aureus (MRSA). The experimental studies and theoretical calculations demonstrate that the V-Fe2 O3 can achieve the localized "capture and killing" bifunction from the spiky morphology and massive reactive oxygen species (ROS) production. The V-Fe2 O3 can reach nearly 100 % bacterial inhibition over a long period by efficiently oxidizing the lipid membrane. Our wound disinfection results identify that the V-Fe2 O3 can not only efficiently eliminate MRSA and their biofilm but also accelerate wound recovery without causing noticeable inflammation and toxicity. This work offers essential insights into the critical roles of V-O-Fe pair sites and localized "capture and killing" in biocatalytic disinfection and provides a promising pathway for the de novo design of efficient artificial peroxidases.

Effectiveness and Respiratory Adverse Events Following Inactivated and mRNA COVID-19 Vaccines in Patients with COPD and Asthma: A Chinese Population-Based Study.

INTRODUCTION: Effectiveness and respiratory adverse events following coronavirus disease-2019 (COVID-19) vaccines have not been well investigated in Chinese patients with chronic obstructive pulmonary disease (COPD) and asthma. METHODS: Using electronic health care records in Hong Kong, we included adults with COPD or asthma or both and hospitalised for severe respiratory exacerbation in a self-controlled case series (SCCS) study between 23/02/2021 and 30/11/2022. Conditional Poisson regression models were used to estimate the incidence of outcomes within exposure periods (28 days after each dose) compared with baseline periods. Cox proportional hazard models evaluated vaccine effectiveness (VE) against COVID-related mortality, hospitalisation, and severe complications, including admission to intensive care units or ventilatory support. The VE assessment was based on vaccine types and the number of doses. RESULTS: In the SCCS, 343 CoronaVac recipients and 212 BNT162b2 recipients were included. No increased risk of outcomes was observed within the exposure periods. In the cohort study, 108,423 and 83,323 patients received ≥ 2 doses of CoronaVac and BNT162b2, respectively. The VE (95% CI) against COVID-related mortality, hospitalisation, and severe complications after two-dose CoronaVac was 77% (74-80%), 18% (6-23%), and 29% (12-43%), respectively, while for the two-dose regimen of BNT162b2, it was 92% (91-94%), 33% (30-37%), and 57% (45-66%), respectively. Higher VE against COVID-related mortality, hospitalisation, and severe complications was found for the three-dose regimen of CoronaVac (94%, 40%, and 71%) and BNT162b2 (98%, 65%, and 83%). Administering a fourth dose of either vaccine showed additional reductions in COVID-related outcomes. CONCLUSIONS: Among people with COPD and asthma, the COVID-19 vaccines CoronaVac and BNT162b2 did not increase severe exacerbations and achieved moderate-to-high effectiveness against COVID-related outcomes. COVID-19 vaccination remains essential and should be encouraged to protect this vulnerable population in future epidemic waves.

METTL14 promotes IL-6-induced viability, glycolysis and inflammation in HaCaT cells via the m6A modification of TRIM27.

Interleukin-6 (IL-6) is a cytokine generated by healthy constituents of the skin, but is also up-regulated by a wide range of skin lesions and inflammatory conditions to trigger cytopathy of skin cells. TRIM27 was identified to contribute to the functional effects of IL-6 on skin cells. However, the underlying mechanism was not clear. Lentivirus infection was used for gene overexpression or silencing. RT-PCR and Western blot were used to respectively assess mRNA and protein levels. Cell viability was assessed by CCK-8 assay. Extracellular flux analysis was used to assess the levels of oxygen consumption rate and extracellular acidification rate. Mouse back skin was treated with imiquimod to produce psoriasis-like inflammation in vivo. Histological assessment and immunohistochemistry staining were respectively applied to analyse lesioned mouse and human skin samples. IL-6-induced increased viability, glycolysis and inflammation in keratinocytes was inhibited both by a chemical methylation inhibitor and by METTL14 knockdown. Further investigation found that METTL14 induces m6A methylation of TRIM27, which is recognized by a m6A reader, IGF2BP2. Elevation of TRIM27 level and activation of IL-6/STAT3 signalling pathway were found in an in vivo psoriasis-like inflammation model, whereas inhibition m6A methylation strongly alleviated the inflammation. Finally, METTL14, TRIM27, STAT3, p-STAT3 and IL-6 expressions were all found to be increased in clinical skin samples of psoriatic patients. Our results unravelled METTL14/TRIM27/IGF2BP2 signalling axis in keratinocyte cytopathy, which plays a critical role in facilitating the activation of IL-6/STAT3 signalling pathway. Our findings should provide inspirations for the design of new therapeutics for skin inflammatory diseases including psoriasis.

Indocyanine green-loaded platelet activated by photodynamic and photothermal effects for selective control of wound repair.

OBJECTIVE: Prompt and effective wound repair is an essential strategy to promote recovery and prevent infection in patients with various types of trauma. Platelets can release a variety of growth factors upon activation to facilitate revascularization and tissue repair, provided that their activation is uncontrollable. The present study is designed to explore the selective activation of platelets by photodynamic and photothermal effects (PDE/PTE) as well as the trauma repair mediated by PDE/PTE. MATERIALS AND METHODS: In the current research, platelets were extracted from the blood of mice. Indocyanine green (ICG) was applied to induce PDE/PTE. The uptake of ICG by platelets was detected by laser confocal microscopy and flow cytometry. The cellular integrity was measured by microscopy. The reactive oxygen species (ROS) generation and temperature of platelets were assayed by 2,7-Dichlorodihydrofluorescein diacetate (DCFH-DA) and temperature detector. The activation of platelets was measured by western blots (WB), dynamic light scattering (DLS), and scanning electron microscopy (SEM). The release of growth factor was detected by enzyme-linked immuno sorbent assay (Elisa), wherein the in vitro cell proliferation was investigated by 5-Ethynyl-2'-deoxyuridine (EDU) assay. The wound infection rates model and histological examination were constructed to assay the ICG-loaded platelet-mediated wound repair. RESULTS: Platelets could load with ICG, a kind of photodynamic and photothermal agent, as carriers and remain intact. Near-infrared (NIR) laser irradiation of ICG-loaded platelets (ICG@PLT) facilitated higher temperature and ROS generation, which immediately activated ICG@PLT, as characterized by increased membrane p-selectin (CD62p), cyclooxygenase-2 (COX-2), thromboxane A2 receptor (TXA2R) expression, elevated hydrated particle size, and prominent aggregation in platelets. Further investigation revealed that massive insulin-like growth factor (IGF) and platelet-derived growth factor (PDGF) were released from the activated ICG@PLT, which also promoted the proliferation of endothelial cells and keratinocytes in co-culture. In consequence, activated platelets and increased neovascularization could be observed in rats with wound infection treated by ICG@PLT in the presence of NIR. More impressively, the hydrogel containing ICG@PLT accelerated wound healing and suppressed inflammation under NIR, exhibiting excellent wound repair properties. CONCLUSION: Taken together, the current work identified that platelets could be activated by PDE/PTE and thereby release growth factor, potentiating wound repair in a controlled manner.

A dehazing method for flight view images based on transformer and physical priori.

Aiming at the problems of local dehazing distortion and incomplete global dehazing of existing algorithms in real airborne cockpit environments, a two-stage dehazing method PhysiFormer combining physical a priori with a Transformer oriented flight perspective was proposed. The first stage used synthetic pairwise data to pre-train the dehazing model. First, a pyramid pooling module (PPM) was introduced in the Transformer for multiscale feature extraction to solve the problem of poor recovery of local details, then a global context fusion mechanism was used to enable the model to better perceive global information. Finally, considering that combining the physical a priori needs to rely on the estimation of the atmosphere light, an encoding-decoding structure based on the residual blocks was used to estimate the atmosphere light, which was then used for dehazing through the atmospheric scattering model for dehazing. The second stage used real images combined with physical priori to optimize the model to better fit the real airborne environment. The experimental results show that the proposed method has better naturalness image quality evaluator (NIQE) and blind/referenceless image spatial quality evaluator (BRISQUE) indexes and exhibits the best dehazing visual effect in the tests of dense haze, non-uniform haze and real haze images, which effectively improves the problems of color distortion and haze residue.