Decellularized Brain Extracellular Matrix Hydrogel Aids the Formation of Human Spinal-Cord Organoids Recapitulating the Complex Three-Dimensional Organization.

The intricate electrophysiological functions and anatomical structures of spinal cord tissue render the establishment of in vitro models for spinal cord-related diseases highly challenging. Currently, both in vivo and in vitro models for spinal cord-related diseases are still underdeveloped, complicating the exploration and development of effective therapeutic drugs or strategies. Organoids cultured from human induced pluripotent stem cells (hiPSCs) hold promise as suitable in vitro models for spinal cord-related diseases. However, the cultivation of spinal cord organoids predominantly relies on Matrigel, a matrix derived from murine sarcoma tissue. Tissue-specific extracellular matrices are key drivers of complex organ development, thus underscoring the urgent need to research safer and more physiologically relevant organoid culture materials. Herein, we have prepared a rat decellularized brain extracellular matrix hydrogel (DBECMH), which supports the formation of hiPSC-derived spinal cord organoids. Compared with Matrigel, organoids cultured in DBECMH exhibited higher expression levels of markers from multiple compartments of the natural spinal cord, facilitating the development and maturation of spinal cord organoid tissues. Our study suggests that DBECMH holds potential to replace Matrigel as the standard culture medium for human spinal cord organoids, thereby advancing the development of spinal cord organoid culture protocols and their application in in vitro modeling of spinal cord-related diseases.

Human Placenta Decellularized Extracellular Matrix Hydrogel Promotes the Generation of Human Spinal Cord Organoids with Dorsoventral Organization from Human Induced Pluripotent Stem Cells.

Spinal cord organoids are of significant value in the research of spinal cord-related diseases by simulating disease states, thereby facilitating the development of novel therapies. However, the complexity of spinal cord structure and physiological functions, along with the lack of human-derived inducing components, presents challenges in the in vitro construction of human spinal cord organoids. Here, we introduce a novel human decellularized placenta-derived extracellular matrix hydrogel (DPECMH) and, combined with a new induction protocol, successfully construct human spinal cord organoids. The human placenta-sourced decellularized extracellular matrix (dECM), verified through hematoxylin and eosin staining, DNA quantification, and immunofluorescence staining, retained essential ECM components such as elastin, fibronectin, type I collagen, laminin, and so forth. The temperature-sensitive hydrogel made from human placenta dECM demonstrated good biocompatibility and promoted the differentiation of human induced pluripotent stem cell (hiPSCs)-derived spinal cord organoids into neurons. It displayed enhanced expression of laminar markers in comparison to Matrigel and showed higher expression of laminar markers compared to Matrigel, accelerating the maturation process of spinal cord organoids and demonstrating its potential as an organoid culture substrate. DPECMH has the potential to replace Matrigel as the standard additive for human spinal cord organoids, thus advancing the development of spinal cord organoid culture protocols and their application in the in vitro modeling of spinal cord-related diseases.

Ligustilide covalently binds to Cys703 in the pre-S1 helix of TRPA1, blocking the opening of channel and relieving pain in rats with acute soft tissue injury.

ETHNOPHARMACOLOGICAL RELEVANCE: The natural anodyne Ligustilide (Lig), derived from Angelica sinensis (Oliv.) Diels and Ligusticum chuanxiong Hort., has been traditionally employed for its analgesic properties in the treatment of dysmenorrhea and migraine, and rheumatoid arthritis pain. Despite the existing reports on the correlation between TRP channels and the analgesic effects of Lig, a comprehensive understanding of their underlying mechanisms of action remains elusive. AIM OF THE STUDY: The objective of this study is to elucidate the mechanism of action of Lig on the analgesic target TRPA1 channel. METHODS: The therapeutic effect of Lig was evaluated in a rat acute soft tissue injury model. The analgesic target was identified through competitive inhibition of TRP channel agonists at the animal level, followed by Fluo-4/Ca2+ imaging on live cells overexpressing TRP proteins. The potential target was verified through in-gel imaging, colocalization using a Lig-derived molecular probe, and a drug affinity response target stability assay. The binding site of Lig was identified through protein spectrometry and further analyzed using molecular docking, site-specific mutation, and multidisciplinary approaches. RESULTS: The administration of Lig effectively ameliorated pain and attenuated oxidative stress and inflammatory responses in rats with soft tissue injuries. Moreover, the analgesic effects of Lig were specifically attributed to TRPA1. Mechanistic studies have revealed that Lig directly activates TRPA1 by interacting with the linker domain in the pre-S1 region of TRPA1. Through metabolic transformation, 6,7-epoxyligustilide (EM-Lig) forms a covalent bond with Cys703 of TRPA1 at high concentrations and prolonged exposure time. This irreversible binding prevents endogenous electrophilic products from entering the cysteine active center of ligand-binding pocket of TRPA1, thereby inhibiting Ca2+ influx through the channel opening and ultimately relieving pain. CONCLUSIONS: Lig selectively modulates the TRPA1 channel in a bimodal manner via non-electrophilic/electrophilic metabolic conversion. The epoxidized metabolic intermediate EM-Lig exerts analgesic effects by irreversibly inhibiting the activation of TRPA1 on sensory neurons. These findings not only highlight the analgesic mechanism of Lig but also offer a novel nucleophilic attack site for the development of TRPA1 antagonists in the pre-S1 region.

PM2.5 exposure upregulates pro-inflammatory protein expression in human microglial cells via oxidant stress and TLR4/NF-κB pathway.

Exposure to ambient PM2.5 is associated with neurodegenerative disorders, in which microglia activation plays a critical role. Thus far, the underlying mechanisms for PM2.5-induced microglia activation have not been well elucidated. In this study, a human microglial cell line (HMC3) was used as the in vitro model to examine the inflammatory effect (hall marker of microglia activation) of PM2.5 and regulatory pathways. The expression of inflammatory mediators including interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) as well as the brain derived neurotrophic factor (BDNF) were determined by ELISA and/or real-time PCR, respectively. Flow cytometry was used to measure the production of intracellular reactive oxygen species (ROS). Western blot was used to measure protein levels of Toll-like receptor 4 (TLR4), NF-κB inhibitor α (IκBα) and COX-2. It was shown that PM2.5 stimulation increased IL-6 and COX-2 expression but decreased BDNF expression in a dose-dependent manner. Further studies showed that PM2.5 triggered the formation of ROS and pre-treatment with the ROS scavenger acetylcysteine (NAC) significantly suppressed PM2.5-induced IL-6 and COX-2 expression. Moreover, the nuclear factor kappa B (NF-κB) inhibitor BAY11-7085 or the TLR4 neutralizing antibody markedly blocked PM2.5-induced IL-6 and COX-2 expression. However, NAC or BAY11-7085 exhibited minimal effect on PM2.5-induced BDNF down-regulation. In addition, pre-treatment with BAY11-7085 or TLR4 neutralizing antibody reduced ROS production induced by PM2.5, and NAC pre-treatment inhibited TLR4 expression and NF-κB activation induced by PM2.5. Collectively, PM2.5 treatment induced IL-6 and COX-2 but suppressed BDNF expression. PM2.5-induced IL-6 and COX-2 expression was mediated by interactive oxidative stress and TLR4/NF-κB pathway.

TAK-242 improves sepsis-associated acute kidney injury in rats by inhibiting the TLR4/NF-κB signaling pathway.

OBJECTIVE: This study was designed to observe the effect of toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway activity on sepsis-associated acute kidney injury (SA-AKI), thereby providing new considerations for the prevention and treatment of SA-AKI. METHODS: The rats were divided into Sham, cecal ligation and puncture (CLP), CLP + vehicle, and CLP + TAK-242 groups. Except the Sham group, a model of CLP-induced sepsis was established in other groups. After 24 h, the indicators related to kidney injury in blood samples were detected. The pathological changes in the kidneys were observed by hematoxylin-eosin staining, and tubular damage was scored. Oxidative stress-related factors, mitochondrial dysfunction-related indicators in each group were measured; the levels of inflammatory factors in serum and kidney tissue of rats were examined. Finally, the expression of proteins related to the TLR4/NF-κB signaling pathway was observed by western blot. RESULTS: Compared with the CLP + vehicle and CLP + TAK-242 groups, the CLP + TAK-242 group reduced blood urea nitrogen (BUN), creatinine (Cr), cystatin-C (Cys-C), reactive oxygen species (ROS), malondialdehyde (MDA), and inflammatory factors levels (p < 0.01), as well as increased superoxide dismutase (SOD) activity of CLP rats (p < 0.01). Additionally, TAK-242 treatment improved the condition of CLP rats that had glomerular and tubular injuries and mitochondrial disorders (p < 0.01). Further mechanism research revealed that TAK-242 can inhibit the TLR4/NF-κB signaling pathway activated by CLP (p < 0.01). Above indicators after TAK-242 treatment were close to those of the Sham group. CONCLUSION: TAK-242 can improve oxidative stress, mitochondrial dysfunction, and inflammatory response by inhibiting the activity of TLR4/NF-κB signaling pathway, thereby preventing rats from SA-AKI.

Enhanced visible light photocatalytic performance of carbon and oxygen co-doped carbon nitride with a three-dimensional structure: Performance and mechanism study.

As a cost-effective photocatalyst, carbon nitride (g-C3N4) holds tremendous promise for addressing energy shortages and environmental pollution. However, its application is limited by disadvantages such as low specific surface area and easy recombination of photogenerated electron-hole pairs. This study introduces C and O co-doped g-C3N4 with a three-dimensional (3D) structure achieved through a straightforward one-step calcination process, demonstrating excellent photocatalytic activity of hydrogen production and oxytetracycline degradation, with superoxide radicals as the primary active species. We propose a plausible enhanced mechanism based on systematic characterizations and density functional theory calculations. The 3D structure confers a substantial specific surface area, enhancing both the adsorption area and active sites of catalysts while bolstering structural stability. Co-doping optimizes the band structure and electric conductivity of the catalyst, facilitating rapid migration of photogenerated charges. The synergistic effects of these enhancements significantly elevate the photocatalytic performance. This study presents a convenient and feasible method for the preparation of dual-regulated photocatalysts with outstanding performance.

Maternal tobacco exposure during pregnancy and atopic dermatitis in offspring: A systematic review and meta-analysis.

The main purpose of this review was to examine the evidence of the relationship between active smoking or passive smoking during pregnancy and atopic dermatitis in offspring. The protocol was written following the PRISMA Checklist and was registered in the PROSPERO database (registration number CRD42022381136). We implemented a comprehensive search in PubMed, Embase and Web of Science databases to identify all potentially related articles from inception through 1 December 2022. We assessed cohort studies and case-control studies using the Newcastle-Ottawa Scale (NOS), and the Joanna Briggs Institute (JBI) critical appraisal tool to assess the quality of cross-sectional studies. Heterogeneity was investigated by using Cochrane Q tests and I2 statistics. In addition, according to the research design, population source and population size, the reasons for the heterogeneity were analysed. A total of 15 observational studies were included in this analysis. Our meta-analysis suggests that atopic dermatitis in offspring is not associated with active smoking during pregnancy (pooled OR, 0.96 [95% CI 0.86-1.07]); however, it is related to passive smoking (OR, 1.52 [95% CI 1.36-1.70]). Passive smoking during pregnancy is associated with an increased risk of eczema development in offspring. More research is needed to explore the risk of active smoking and eczema development in offspring, especially the association between measurements of pregnancy cotinine levels in maternal body fluids and AD in offspring.

A novel method for multi-pollutant monitoring in water supply systems using chemical machine vision.

Drinking water is vital for human health and life, but detecting multiple contaminants in it is challenging. Traditional testing methods are both time-consuming and labor-intensive, lacking the ability to capture abrupt changes in water quality over brief intervals. This paper proposes a direct analysis and rapid detection method of three indicators of arsenic, cadmium, and selenium in complex drinking water systems by combining a novel long-path spectral imager with machine learning models. Our technique can obtain multiple parameters in about 1 s. The experiment involved setting up samples from various drinking water backgrounds and mixed groups, totaling 9360 injections. A raw visible light source ranging from 380 to 780 nm was utilized, uniformly dispersing light into the sample cell through a filter. The residual beam was captured by a high-definition camera, forming a distinctive spectrum. Three deep learning models-ResNet-50, SqueezeNet V1.1, and GoogLeNet Inception V1-were employed. Datasets were divided into training, validation, and test sets in a 6:2:2 ratio, and prediction performance across different datasets was assessed using the coefficient of determination and root mean square error. The experimental results show that a well-trained machine learning model can extract a lot of feature image information and quickly predict multi-dimensional drinking water indicators with almost no preprocessing. The model's prediction performance is stable under different background drinking water systems. The method is accurate, efficient, and real-time and can be widely used in actual water supply systems. This study can improve the efficiency of water quality monitoring and treatment in water supply systems, and the method's potential for environmental monitoring, food safety, industrial testing, and other fields can be further explored in the future.

ANXA3 interference inactivates ERK/ELK1 pathway to mitigate inflammation and apoptosis in sepsis-associated acute lung injury.

Acute lung injury (ALI) is a prevailing and deadly complication of sepsis coupled with increasing incidence and fatality rate. Annexin A3 (ANXA3) has been unraveled to be upregulated during sepsis. This study purposed to assess the role and the mechanism of ANXA3 in sepsis-induced ALI. After the construction of mouse model of sepsis, the pathological changes of mice lung tissues were estimated by H&E staining. ANXA3 expression in mice lung tissues and serum was examined. The degree of pulmonary edema and the levels of inflammatory factors in bronchoalveolar lavage fluid (BALF) were analyzed. In lipopolysaccharide (LPS)-induced mouse ALI model in vitro, CCK-8 assay measured cell viability and flow cytometry analysis detected cell apoptosis. Besides, ELISA assay detected the release of inflammatory cytokines. Western blot analyzed the expression of proteins associated with inflammation, apoptosis and extracellular-signal-regulated kinase (ERK)/ETS-like gene 1 (ELK1) signaling. Results revealed that ANXA3 was overexpressed in the lung tissues and serum of septic mice. Following the knockdown of ANXA3, sepsis-induced lung injury was alleviated, manifested as reduced lung edema, decreased inflammatory cell infiltration and inhibited cell apoptosis. Additionally, ANXA3 silence blocked ERK/ELK1 signaling both in sepsis mouse models and in vitro model of ALI induced by lipopolysaccharide (LPS). Moreover, the inhibitory effects of ANXA3 silencing on ERK/ELK1 signaling activation, the viability damage, inflammation and apoptosis in LPS-induced mouse ALI model in vitro were partially reversed by ERK activator. Collectively, depletion of ANXA3 exerted suppressive effects on the inflammation and apoptosis in sepsis-induced ALI through blocking ERK/ELK1 signaling.

Plasma THBS1 as a predictive biomarker for poor prognosis and brain metastasis in patients with HER2-enriched breast cancer.

BACKGROUND: Thrombospondin-1 (THBS1) is a secretory adhesive glycoprotein involved in the progression of multiple malignancies, including breast cancer. However, the clinical significance and prognostic role of plasma THBS1 in breast cancer have yet to be clarified. METHODS: Plasma THBS1 levels in 627 breast cancer patients were analyzed by enzyme-linked immunosorbent assay. Bone marrow blood was drawn from the anterior/posterior superior iliac spine to detect the presence of disseminated tumor cells (DTCs). The effects of plasma THBS1 on the clinicopathological characteristics and survival prediction of breast cancer patients were explored. RESULTS: Plasma THBS1 did not correlate with overall survival, breast cancer-specific survival (BCSS), and distant disease-free survival (DDFS) in the entire breast cancer cohort. Notably, HER2-enriched patients with high-plasma THBS1 levels had significantly shorter BCSS (P = 0.027) and DDFS (P = 0.011) than those with low levels. Multivariate analyses revealed that plasma THBS1 was an independent prognostic marker of BCSS (P = 0.026) and DDFS (P = 0.007) in HER2-enriched patients. THBS1 levels were 24% higher in positive DTC patients than in negative DTC patients (P = 0.031), and high levels were significantly associated with poor BCSS in positive DTC patients (HR 2.08, 95% CI 1.17-3.71; P = 0.019). Moreover, high-plasma THBS1 levels were specifically associated with an increased occurrence of brain metastasis in HER2-enriched patients (P = 0.041). CONCLUSION: These findings suggest that plasma THBS1 may be serving as an unfavorable prognosis predictor for HER2-enriched breast cancer and justifies the need for further research.

Grape seed proanthocyanidin extract alleviates inflammation in experimental colitis mice by inhibiting NF-κB signaling pathway.

Ulcerative colitis (UC) is a complex inflammatory disease of colorectum that induces abnormal immune responses and severely affects the quality of life of the patients. Grape seed proanthocyanidin extract (GSPE) exerts anti-inflammatory and antioxidant functions in many inflammatory diseases. The objective of this study was to investigate the potential therapeutic effects and underlying mechanisms of GSPE in UC using a dextran sodium sulfate (DSS)-induced mouse UC model and a lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage model. In this study, we found that the GSPE markedly prevented DSS-induced weight loss and colon length shortening in UC mice. Further investigations showed that GSPE significantly attenuated the expression of pro-inflammatory cytokines TNF-α, IL-6, and IL-1ß, and elevated the expression of anti-inflammatory cytokine IL-10 in the colon tissues and serum of DSS-induced colitis mice by suppressing NF-κB signaling pathway. Furthermore, LPS-induced inflammation in RAW264.7 cells was also reversed by GSPE. Taken together, our results confirm that GSPE can ameliorate inflammatory response in experimental colitis via inhibiting NF-κB signaling pathway. This study advances the research progress on a potentially effective therapeutic strategy for inflammatory bowel diseases.

Association of short-term PM2.5 exposure with airway innate immune response, microbiota and metabolism alterations in human airways.

Exposure to fine particulate matter (PM2.5) has been associated with impaired airway innate immunity, leading to diverse lung disorders. However, the mechanisms of the adverse effects of PM2.5 on the airway innate immune system has not been adequately elucidated. This study aimed to investigate the association between short-term exposure to ambient PM2.5 and airway innate immune responses. A panel study of 53 undergraduate students was conducted in November 2020 and April 2021. Levels of airway innate immune biomarkers including interleukin-1ß (IL-1ß), IL-4, IL-6, IL-8, IL-17, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), myeloperoxidase (MPO), and matrix metalloproteinase-9 (MMP-9) in induced sputum were measured, and airway microbiota and metabolites examined. Linear mixed-effect model was used to evaluate the effects of short-term exposure to PM2.5 on the above-listed airway immune biomarkers. The results indicated that for every 10 µg/m3 increase in PM2.5 concentration (at lag3), was associated with an increase of 21.3 % (5.4 %-37.1 %), 26.2 % (0.30 %-52.1 %), 22.4 % (0.70 %-44.2 %), 27.4 % (6.6 %-48.3 %), 18.3 % (4.6 %-31.9 %), 3.9 % (0.20 %-7.6 %) or 2.4 % (0.10 %-4.7 %) in IL-6, TNF-α, IL-17, IL-4, IFN-γ, MPO, or MMP-9 levels, respectively. Meanwhile, exposure to higher levels of ambient PM2.5 was found to significantly modulate airway microbiota and metabolite profile. Specifically, Prevotella and Fusobacterium, as well as 96 different metabolites were associated with PM2.5 levels. The metabolic pathways associated with these metabolites mainly included amino acid biosynthesis and metabolism. Notably, PM2.5 exposure-induced alterations of some airway microbiota were significantly correlated with specific airway metabolic change. Taken together, these results demonstrated that short-term exposure to PM2.5 was associated with alterations of airway immune response, microbial dysbiosis and changes of metabolites. This study provided insights into the mechanisms underlying PM2.5-induced airway innate immune responses.

Assessment of Human Exposure to Traditional and Novel Organophosphate Esters via Multiple Personal Matrices.

Herein, 16 traditional and 13 novel organophosphate esters (OPEs) in skin wipes, personal PM2.5, sputum, and nails (fingernails and toenails) and 7 OPE metabolites in urine synchronously obtained from 64 college students were analyzed. Similar compositional profiles of the OPEs were found in skin wipes and nails and in personal PM2.5 and induced sputum. Significant correlations were observed between the concentrations of high-lipophilicity low-volatility OPEs in skin wipes and nails and between the concentrations of high-volatility low-lipophilicity OPEs in personal PM2.5 and sputum. These results imply that OPEs in fingernails and toenails may mainly come from external sources rather than internal exposure, and human nails and sputum can be used as indicators of human exposure to OPEs. A comparison between the daily exposure doses of the OPEs in personal PM2.5 and sputum shows that more volatile compounds may have higher inhalation bioavailability, which should be considered to improve the accuracy of inhalation exposure assessments. According to comprehensive external and internal exposure assessment, dermal absorption may be a more dominant pathway than inhalation, and skin wipes may be the best representative environmental matrix of human exposure to OPEs.

Sfrp1 as a Pivotal Paracrine Factor in the Trained Pericardial Stem Cells that Foster Reparative Activity.

Tissue damage often induces local inflammation that in turn dictates a series of subsequential responses, such as stem cell activation and growth, to maintain tissue homeostasis. The aim of the study is to testify the possibility of using inflammation-trained stem cells as optimal donor cells to augment the efficacy of cell therapy. The pericardial stem/stromal cells derived from the animals after myocardial infarction (MI-pSC) showed an enhanced myogenic potential and augmented reparative activity after transplantation in the injured hearts, as compared to the Sham-pSC. Bulk RNA-Seq analysis revealed significant upregulation of a panel of myogenic and trophic genes in the MI-pSC and, notably, Sfrp1 as an important anti-apoptotic factor induced robustly in the MI-pSC. Injection of the MI-pSC yielded measurable numbers of surviving cardiomyocytes (Tunel and Casp-3 negative) within the infarct area, but the effects were significantly diminished by siRNA-based silence of Sfrp1 gene in the pSC. Primed Sham-pSC with pericardial fluid from MI rats mimicked the upregulation of Sfrp1 and enhanced myogenic potential and reparative activity of pSC. Taken together, our results illustrated the inflammation-trained pSC favor a reparative activity through upregulation of Sfrp1 gene that confers anti-apoptotic activity in the injured cardiomyocytes. Therefore, the active form of stem cells may be used as a cardiac protective agent to boost therapeutical potential of stem cells.

Association of the m6 A reader IGF2BP3 with tumor progression and brain-specific metastasis in breast cancer.

BACKGROUND: This study aimed to determine the role of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), an N6 -methyladinosine reader, in the progression and distant metastasis of breast cancer. METHODS: IGF2BP3 expression was assessed in 152 pairs of breast cancer and adjacent normal tissue (ANT) by real-time quantitative polymerase chain reaction and in 561 cases of breast cancer and 163 cases of ANT by immunohistochemistry. Survival curves were estimated using the Kaplan-Meier method and then compared statistically using the log-rank test. The prognostic role of IGF2BP3 was determined by Cox regression analysis. RESULTS: Analysis of public gene data sets revealed that IGF2PB3 predicted distant metastasis in breast cancer and was highly correlated with brain metastasis. In the clinical retrospective cohort, the positive rate of IGF2BP3 increased gradually with breast cancer progression. Positive IGF2BP3 expression was related to poor distant metastasis-free survival (DMFS, p = .030) and Cox regression analysis identified IGF2BP3 as an independent risk factor for DMFS (hazard ratio, 1.876; 95% confidence interval, 1.128-3.159; p = .019). Positive IGF2BP3 expression was markedly related to breast cancer brain metastasis (p = .011) but not to lung and bone metastasis. Moreover, patients with IGF2BP3-positive brain metastasis had lower survival than patients with IGF2BP3-negative brain metastasis (p = .041). Gene expression profiling results indicated that high IGF2BP3 expression was associated with the PD-1 checkpoint pathway, HER2-HER3 signaling, and epithelial-mesenchymal transition. CONCLUSIONS: IGF2BP3 may serve as a novel predictive biomarker and a potential therapeutic target for breast cancer brain metastasis, which warrants further investigation. PLAIN LANGUAGE SUMMARY: As an m6 A reader, IGF2BP3 is dysregulated and implicated in various cancers but its role in breast cancer has not been fully clarified. In this study, we found that IGF2BP3 was upregulated in breast cancer and IGF2BP3 expression increased gradually during breast cancer progression. IGF2BP3 expression exerted no effect on the overall survival and breast cancer-specific survival of breast cancer patients; however, IGF2BP3-positive patients were more likely to develop distant metastasis than IGF2BP3-negative patients. In addition, IGF2BP3 was associated with brain-specific metastasis in breast cancer patients. These findings warrant further investigation because they provide a rationale for novel predictive or therapeutic approaches.

Curcumin alleviates traumatic brain injury induced by gas explosion through modulating gut microbiota and suppressing the LPS/TLR4/MyD88/NF-κB pathway.

Gas explosions (GE) are a prevalent and widespread cause of traumatic brain injury (TBI) in coal miners. However, the impact and mechanism of curcumin on GE-induced TBI in rats remain unclear. In this study, we simulated GE-induced TBI in rats and administered curcumin orally at a dose of 100 mg/kg every other day for 7 days to modulate the gut microbiota in TBI rats. We employed 16S rRNA sequencing and LC-MS/MS metabolomic analysis to investigate changes in the intestinal flora and its metabolic profile. Additionally, we utilized ELISA, protein assays, and immunohistochemistry to assess neuroinflammatory signaling molecules for validation. In a rat TBI model, GE resulted in weight loss, pathological abnormalities, and cortical hemorrhage. Treatment with curcumin significantly mitigated histological abnormalities and microscopic mitochondrial structural changes in brain tissue. Furthermore, curcumin treatment markedly ameliorated GE-induced brain dysfunction by reducing the levels of several neuroinflammatory signaling molecules, including neuron-specific enolase, interleukin (IL)-1ß, IL-6, and cryptothermic protein 3. Notably, curcumin reshaped the gut microbiome by enhancing evenness, richness, and composition. Prevotella_9, Alloprevotella, Bacilli, Lactobacillales, Proteobacteria, and Gammaproteobacteria were identified as prominent members of the gut microbiota, increasing the linear discriminant analysis scores and specifically enhancing the abundance of bacteria involved in the nuclear factor (NF)-κB signaling pathway, such as Lachnospiraceae and Roseburia. Additionally, there were substantial alterations in serum metabolites associated with metabolic NF-κB signaling pathways in the model group. Curcumin administration reduced serum lipopolysaccharide levels and downregulated downstream Toll-like receptor (TLR)4/myeloid differentiation primary response 88 (MyD88)/NF-κB signaling. Furthermore, curcumin alleviated GE-induced TBI in rats by modulating the gut microbiota and its metabolites. Based on these protective effects, curcumin may exert its influence on the gut microbiota and the TLR4/MyD88/NF-κB signaling pathways to ameliorate GE-induced TBI.

DEHP and DINP accelerate aging effects in male and female of Drosophila melanogaster depend on AKT/FOXO pathway.

Phthalates are commonly used as plasticizers. Numerous studies have focused on endocrine, reproductive, and developmental toxicity of phthalates exposure to male organisms. In recent years, some studies looking into the aging effects of phthalates exposure in D. melanogaster showed discrepant results. In this study, we compared the different concentrations of Di(2-ethylhexyl) phthalate (DEHP) and di-isononyl phthalate (DINP) for acute and chronic treatment for different gender D. melanogaster and explored the potential mechanism of DEHP and DINP exposure. The results showed that acute exposure to DEHP or DINP at a high dose significantly decreased the lifespan of female and male D. melanogaster under HFD stress. Chronic exposure significantly decreased the lifespan of flies in all exposure groups except for the low-dose DINP exposure female group. Among them, in the normal feeding group, we found that female flies seemed to be more resistant to DEHP or DINP exposure. Meanwhile, the locomotion ability and fertility of flies exhibited a dose-dependent decline. Furthermore, phthalates did not significantly reduce the lifespan or health status of akt and foxo mutant flies in the mutant fly assays, and real-time quantitative-PCR (q-PCR) data revealed akt and foxo significant change with 10 µM DEHP or DINP treatment. This suggests that akt and foxo played a role in the process by which DEHP and DINP caused age-related declines in D. melanogaster.

CT-Net: Asymmetric compound branch Transformer for medical image segmentation.

The Transformer architecture has been widely applied in the field of image segmentation due to its powerful ability to capture long-range dependencies. However, its ability to capture local features is relatively weak and it requires a large amount of data for training. Medical image segmentation tasks, on the other hand, demand high requirements for local features and are often applied to small datasets. Therefore, existing Transformer networks show a significant decrease in performance when applied directly to this task. To address these issues, we have designed a new medical image segmentation architecture called CT-Net. It effectively extracts local and global representations using an asymmetric asynchronous branch parallel structure, while reducing unnecessary computational costs. In addition, we propose a high-density information fusion strategy that efficiently fuses the features of two branches using a fusion module of only 0.05M. This strategy ensures high portability and provides conditions for directly applying transfer learning to solve dataset dependency issues. Finally, we have designed a parameter-adjustable multi-perceptive loss function for this architecture to optimize the training process from both pixel-level and global perspectives. We have tested this network on 5 different tasks with 9 datasets, and compared to SwinUNet, CT-Net improves the IoU by 7.3% and 1.8% on Glas and MoNuSeg datasets respectively. Moreover, compared to SwinUNet, the average DSC on the Synapse dataset is improved by 3.5%.

CR-Conformer: a fusion network for clinical skin lesion classification.

Deep convolutional neural network (DCNN) models have been widely used to diagnose skin lesions, and some of them have achieved diagnostic results comparable to or even better than dermatologists. Most publicly available skin lesion datasets used to train DCNN were dermoscopic images. Expensive dermoscopic equipment is rarely available in rural clinics or small hospitals in remote areas. Therefore, it is of great significance to rely on clinical images for computer-aided diagnosis of skin lesions. This paper proposes an improved dual-branch fusion network called CR-Conformer. It integrates a DCNN branch that can effectively extract local features and a Transformer branch that can extract global features to capture more valuable features in clinical skin lesion images. In addition, we improved the DCNN branch to extract enhanced features in four directions through the convolutional rotation operation, further improving the classification performance of clinical skin lesion images. To verify the effectiveness of our proposed method, we conducted comprehensive tests on a private dataset named XJUSL, which contains ten types of clinical skin lesions. The test results indicate that our proposed method reduced the number of parameters by 11.17 M and improved the accuracy of clinical skin lesion image classification by 1.08%. It has the potential to realize automatic diagnosis of skin lesions in mobile devices.

The relationship between air pollution and depression and anxiety disorders - A systematic evaluation and meta-analysis of a cohort-based study.

OBJECTIVE: To explore the correlation between air pollution and the onset of depression and anxiety disorders, to draw more comprehensive and integrated conclusions, and to provide recommendations for maintaining mental health and developing policies to reduce mental health risks caused by air pollution. METHODS: Meta-analysis of cohort study articles exploring the relationship between air pollution and depression or anxiety disorders included in Pubmed, Web Of Science, CNKI, and Wan Fang database before October 31, 2022, and subgroup analysis of the association between air pollution and depression and anxiety disorders regarding the air pollutants studied, the study population, and Publication bias analysis and sensitivity analysis. RESULTS: A total of 25 articles meeting the criteria were included in this study, including 23 articles examining the relationship between air pollution and depression and 5 articles examining the relationship between air pollution and anxiety disorders. The results of the meta-analysis were based on the type of pollutant and showed that there was a high degree of heterogeneity among the studies on the relationship between air pollution and depression and a significant heterogeneity among the studies on PM2.5 and the risk of anxiety disorders (I2 = 71%, p < .01), so a random-effects model was selected for the analysis. CO, O3, and SO2 and depression onset had combined RR values of 1.10 (1.00, 1.20), 1.06 (0.87, 1.29), 1.17 (1.06, 1.31), 1.19 (0.90, 1.58), 1.03 (0.99, 1.07), and 1.09 (0.97, 1.24), respectively, and PM2.5 and anxiety The combined RR value for morbidity was 1.10 (0.99, 1.22). The results of sensitivity analysis showed that the combined results were stable and reliable. The results of Egger regression method test showed that none of them had significant publication bias (p > .05). LIMITATION: Combined exposure to air pollutants on depression and anxiety, further studies by other researchers are needed in the future. CONCLUSIONS: PM2.5 and NO2 exposure, especially long-term exposure, may be associated with the onset of depression, and no association was found for the time being between PM10, CO, O3, SO2 exposure and depression and PM2.5 exposure and anxiety disorders.