Effect of PEAR1, PTGS1 gene polymorphisms on the recurrence of aspirin-treated patients with ischemic stroke in the Han population of China: A 4-year follow-up study.

Platelet endothelial aggregation receptor 1 (PEAR1) and prostaglandin endoperoxide synthase 1 (PTGS1) polymorphisms can affect laboratory aspirin resistance. However, the impact of genetic polymorphisms on the recurrence of ischemic stroke (IS) patients treated with aspirin is not fully understood. This study aimed to examine the relationship between gene polymorphisms of PEAR1 and PTGS1 and IS recurrence in patients treated with aspirin. Peripheral blood samples were collected from 174 patients with nonrecurrent IS and 34 with recurrent IS after aspirin treatment. Follow-up was performed on all patients. PEAR1 rs12041331 and PTGS1 rs10306114 polymorphisms were determined using the PCR fluorescence probe method. And the correlations of them with the clinical characteristics were examined by multivariable logistic regression analysis. The distribution frequencies of PEAR1 rs12041331 and PTGS1 rs10306114 genotypes were in Hardy-Weinberg equilibrium, and there was no significant difference in the distribution of PEAR1 rs12041331 polymorphism. Compared to the nonrecurrent group, the AA genotype of the PTGS1 polymorphism was more frequent in the recurrent group (59.77% vs 35.29%, P = .003), and the A allele also showed a higher frequency than the G allele in the recurrent group (P = .001). Multivariable logistic regression analysis showed that smoking (OR = 5.228, 95% CI: 1.938-14.102, P = .001), coronary heart disease (OR = 4.754, 95% CI: 1.498-15.089, P = .008), and the polymorphism at PTGS1(A>G) AA/AG + GG (OR = 2.955, 95% CI: 1.320-6.616, P = .008) were independently associated with IS recurrence in Chinese patients. Our findings suggested that PTGS rs10306114 polymorphisms should receive more attention in the use of aspirin in patients with IS.

Digital exclusion and cognitive impairment in older people: findings from five longitudinal studies.

OBJECTIVES: Older people are more likely to have digital exclusion, which is associated with poor health. This study investigated the relationship between digital exclusion and cognitive impairment in older adults from 23 countries across five longitudinal surveys. DESIGN AND MEASUREMENTS: Digital exclusion is defined as self-reported non-use of the Internet. We assessed cognitive impairment on three dimensions: orientation, memory, and executive function. We used generalized estimation equations fitting binary logistic regression with exchangeable correlations to study the relationship between digital exclusion and cognitive impairment, and apply the minimum sufficiently adjusted set of causally directed acyclic graphs as the adjusted variable. SETTING AND PARTICIPANTS: We pooled a nationally representative sample of older adults from five longitudinal studies, including the China Health and Retirement Longitudinal study (CHARLS), the English Longitudinal Study of Ageing (ELSA), the Health and Retirement Study (HRS), the Mexican Health and Ageing Study (MHAS) and the Survey of Health, Ageing and Retirement in European (SHARE). RESULTS: We included 62,413 participants from five longitudinal studies. Digital exclusion varied by country, ranging from 21.69% (SHARE) in Denmark to 97.15% (CHARLS) in China. In the original model, digital exclusion was significantly associated with cognitive impairment in all five studies. In the adjusted model, these associations remained statistically significant: CHARLS (Odds ratio [OR] = 2.81, 95% confidence interval [CI] 1.84-4.28, ELSA (1.92 [1.70-2.18]), HRS(2.48[2.28-2.71), MHAS (1.92 [1.74-2.12]), and SHARE (2.60 [2.34-2.88]). CONCLUSION: Our research shows that a significant proportion of older people suffer from digital exclusion, especially in China. Digital exclusion was positively correlated with cognitive impairment. These findings suggest that digital inclusion could be an important strategy to improve cognitive function and reduce the risk of cognitive impairment in older adults.

Nicotine inhalant via E-cigarette facilitates sensorimotor function recovery by upregulating neuronal BDNF-TrkB signalling in traumatic brain injury.

BACKGROUND AND PURPOSE: Traumatic brain injury (TBI) causes lifelong physical and psychological dysfunction in affected individuals. The current study investigated the effects of chronic nicotine exposure via E-cigarettes (E-cig) (vaping) on TBI-associated behavioural and biochemical changes. EXPERIMENTAL APPROACH: Adult C57/BL6J male mice were subjected to controlled cortical impact (CCI) followed by daily exposure to E-cig vapour for 6 weeks. Sensorimotor functions, locomotion, and sociability were subsequently evaluated by nesting, open field, and social approach tests, respectively. Immunoblots were conducted to examine the expression of mature brain-derived neurotrophic factor (mBDNF) and associated downstream proteins (p-Erk, p-Akt). Histological analyses were performed to evaluate neuronal survival and neuroinflammation. KEY RESULTS: Post-injury chronic nicotine exposure significantly improved nesting performance in CCI mice. Histological analysis revealed increased survival of cortical neurons in the perilesion cortex with chronic nicotine exposure. Immunoblots revealed that chronic nicotine exposure significantly up-regulated mBDNF, p-Erk and p-Akt expression in the perilesion cortex of CCI mice. Immunofluorescence microscopy indicated that elevated mBDNF and p-Akt expression were mainly localized within cortical neurons. Immunolabelling of Iba1 demonstrated that chronic nicotine exposure attenuated microglia-mediated neuroinflammation. CONCLUSIONS AND IMPLICATIONS: Post-injury chronic nicotine exposure via vaping facilitates recovery of sensorimotor function by upregulating neuroprotective mBDNF/TrkB/Akt/Erk signalling. These findings suggest potential neuroprotective properties of nicotine despite its highly addictive nature. Thus, understanding the multifaceted effects of chronic nicotine exposure on TBI-associated symptoms is crucial for paving the way for informed and properly managed therapeutic interventions.

Transfer learning enables identification of multiple types of RNA modifications using nanopore direct RNA sequencing.

Nanopore direct RNA sequencing (DRS) has emerged as a powerful tool for RNA modification identification. However, concurrently detecting multiple types of modifications in a single DRS sample remains a challenge. Here, we develop TandemMod, a transferable deep learning framework capable of detecting multiple types of RNA modifications in single DRS data. To train high-performance TandemMod models, we generate in vitro epitranscriptome datasets from cDNA libraries, containing thousands of transcripts labeled with various types of RNA modifications. We validate the performance of TandemMod on both in vitro transcripts and in vivo human cell lines, confirming its high accuracy for profiling m6A and m5C modification sites. Furthermore, we perform transfer learning for identifying other modifications such as m7G, Ψ, and inosine, significantly reducing training data size and running time without compromising performance. Finally, we apply TandemMod to identify 3 types of RNA modifications in rice grown in different environments, demonstrating its applicability across species and conditions. In summary, we provide a resource with ground-truth labels that can serve as benchmark datasets for nanopore-based modification identification methods, and TandemMod for identifying diverse RNA modifications using a single DRS sample.

A new mode for the diagnosis of angioimmunoblastic T-cell lymphoma.

In order to explore a new mode for the diagnosis of angioimmunoblastic T-cell lymphoma (AITL), 31 cases of AITL and 28 cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) were used as the study subjects. Identifying T follicular helper (TFH) cells with CD4, CD10, Bcl-6, and PD-1, identifying proliferative B cells with CD20 and EZH2, identifying proliferative follicular dendritic cells (FDCs) with CD21 and CD23, and analyzing the value of TFH/B/FDC proliferation and immunolocalization in the diagnosis of AITL. (1) Outside the inherent lymphoid follicles, simultaneous proliferation of TFH/B/FDC (a new diagnostic mode) were observed in AITL [83.87%; 26/31], with their immunolocalizations in the same site [83.87%; 26/31], while this phenomenon was not observed in 28 cases of PTCL-NOS (P<0.05). (2) The sensitivity and specificity of using this new mode to diagnose AITL were both high (83.87%, 100%), which was superior to CD2 (100%, 0%), CD3 (100%, 0%), CD4 (100%, 32.14%), CD5 (100%, 25%), CD10 (61.9%, 100%), Bcl-6 (42.86%, 100%), PD-1 (83.87%, 96.43%), and its Youden Index (0.84) was the highest. The areas under the curve (AUC) of CD10, Bcl-6, PD-1, and new mode to diagnosis AITL were 0.81, 0.71, 0.90, and 0.92, respectively, while the new mode had the highest AUC. The simultaneous proliferation of TFH/B/FDC cells outside the inherent lymphoid follicles can be used to assist in the diagnosis of AITL, and the simultaneous spatiotemporal proliferation of TFH/B/FDC cells is a specific immunomorphology of AITL.

Characterization of Therapeutic Antibody Charge Heterogeneity Under Stress Conditions by Microfluidic Capillary Electrophoresis Coupled with Mass Spectrometry.

Therapeutic antibodies are a major class of biopharmaceutics that are applied in disease treatment because of their many advantages, including high specificity and high affinity to molecular targets. Between their production and administration, therapeutic antibodies are exposed to multiple stress conditions. Forced degradation and stress stability studies are conducted to simulate the risk of degradation and the effects of these stresses, thereby enhancing understanding of the drug product to support strategies to mitigate the impact from stressed conditions. These types of studies are also routinely conducted to evaluate product comparability when major process changes are implemented during the production. Charge variant analysis helps understand the changes in the electrostatic environment of biotherapeutics and can uncover underlying molecular level alterations associated with charge variants. Herein, we used ZipChip native capillary electrophoresis-mass spectrometry (nCE-MS) to elucidate the changes in charge variant profiles at the molecular level. In two case studies under thermal stress conditions, we observed that charge variants arose from both post-translational modifications (including deamidation, oxidation, and pyroglutamate formation) and sequence truncations at the hinge regions. Under oxidative stress conditions, oxidation was found to be the major contributor to the changes in the charge variant profiles. Under pH stress conditions, the changes in the charge variant profile were due to increased levels of deamidation, oxidation, and pyroglutamate formation. ZipChip nCE-MS analysis enables identification of charge variant species under various stress conditions, thus supporting process and formulation development of biotherapeutics.

Ionic liquid catalyzed low-temperature hydrothermal carbonization of sewage sludge to produce hydrochar with low heavy metal content and positive energy recovery.

An ionic liquid (IL, [DMAPA]HSO4) was prepared to facilitate the removal of heavy metals by hydrothermal carbonization (HTC) in sewage sludge (SS) and to obtain a positive energy recovery (ER, (Energyoutput/Energyinput - 1) > 0). The results found that the removal efficiencies of the Fe, Mn, Zn, Co, and Cd from SS exceeded 75 % with positive ER (6 %) at 20 wt% IL dosage (IL:SS). IL promoted the HTC reactions of proteins and polysaccharides to produce fixed carbon and small molecule polymers. The process mainly relies on IL to catalyze the dehydration and graphitization of SS and to destroy the heavy metal binding sites such as carboxyl and hydroxyl groups. Additionally, IL aids in constructing the macropore structures in hydrochar, thereby facilitating the release of heavy metals and water during the HTC process. This discovery holds promise for removing heavy metals from SS by one-pot HTC processes with positive energy recovery.

A Fully Automated Online Enrichment and Separation System for Highly Reproducible and In-Depth Analysis of Intact Glycopeptide.

A fully automated online enrichment and separation system for intact glycopeptides, named AutoGP, was developed in this study by integrating three different columns in a nano-LC system. Specifically, the peptide mixture from the enzymatic digestion of a complex biological sample was first loaded on a hydrophilic interaction chromatography (HILIC) column. The nonglycopeptides in the sample were washed off the column, and the glycopeptides retained by the HILIC column were eluted to a C18 trap column to achieve an automated glycopeptide enrichment. The enriched glycopeptides were further eluted to a C18 column for separation, and the separated glycopeptides were eventually analyzed by using an orbitrap mass spectrometer (MS). The optimal operating conditions for AutoGP were systemically studied, and the performance of the fully optimized AutoGP was compared with a conventional manual system used for glycopeptide analysis. The experimental evaluation shows that the total number of glycopeptides identified is at least 1.5-fold higher, and the median coefficient of variation for the analyses is at least 50% lower by using AutoGP, as compared to the results acquired by using the manual system. In addition, AutoGP can perform effective analysis even with a 1-µg sample amount, while a 10-µg sample at least will be needed by the manual system, implying an order of magnitude better sensitivity of AutoGP. All the experimental results have consistently proven that AutoGP can be used for much better characterization of intact glycopeptides.

The Critical Analysis of Membranes toward Sustainable and Efficient Vanadium Redox Flow Batteries.

Vanadium redox flow batteries (VRFB) are a promising technology for large-scale storage of electrical energy, combining safety, high capacity, ease of scalability, and prolonged durability; features which have triggered their early commercial implementation. Furthering the deployment of VRFB technologies requires addressing challenges associated to a pivotal component: the membrane. Examples include vanadium crossover, insufficient conductivity, escalated costs, and sustainability concerns related to the widespread adoption of perfluoroalkyl-based membranes, e.g., perfluorosulfonic acid (PFSA). Herein, recent advances in high-performance and sustainable membranes for VRFB, offering insights into prospective research directions to overcome these challenges, are reviewed. The analysis reveals the disparities and trade-offs between performance advances enabled by PFSA membranes and composites, and the lack of sustainability in their final applications. The potential of PFSA-free membranes and present strategies to enhance their performance are discussed. This study delves into vital membrane parameters to enhance battery performance, suggesting protocols and design strategies to achieve high-performance and sustainable VRFB membranes.

Responses of Protozoan Communities to Multiple Environmental Stresses (Warming, Eutrophication, and Pesticide Pollution).

To explore the impacts of multiple environmental stressors on animal communities in aquatic ecosystems, we selected protozoa-a highly sensitive group of organisms-to assess the effect of environmental change. To conduct this simulation we conducted a three-factor, outdoor, mesocosm experiment from March to November 2021. Changes in the community structure and functional group composition of protozoan communities under the separate and combined effects of these three environmental stressors were investigated by warming and the addition of nitrogen, phosphorus, and pesticides. The results were as follows: (1) Both eutrophication and pesticides had a considerable promotional effect on the abundance and biomass of protozoa; the effect of warming was not considerable. When warming was combined with eutrophication and pesticides, there was a synergistic effect and antagonistic effect, respectively. (2) Eutrophication promoted α diversity of protozoa and affected their species richness and dominant species composition; the combination of warming and pesticides remarkably reduced the α diversity of protozoa. (3) Warming, eutrophication, and pesticides were important factors affecting the functional groups of protozoa. Interaction among different environmental factors could complicate changes in the aquatic ecological environment and its protozoan communities. Indeed, in the context of climate change, it might be more difficult to predict future trends in the protozoan community. Therefore, our results provide a scientific basis for the protection and restoration of shallow lake ecosystems; they also offer valuable insights in predicting changes in shallow lakes.

Low gelatin concentration assisted cellulose nanocrystals stabilized high internal phase emulsion: The key role of interaction.

Low concentrations of gelatin (0.02-0.20 wt%) were applied to regulate the surface and interface properties of CNC (0.50 wt%) by forming CNC/G complexes. As gelatin concentration increased from 0 to 0.20 wt%, the potential value of CNC/G gradually changed from -44.50 to -17.93 mV. Additionally, various gelatin concentrations led to micromorphology changes of CNC/G complexes, with the formation of particle interconnection at gelatin concentration of 0.10 wt%, followed by network structure and enhanced aggregation at gelatin concentration of 0.15 and 0.20 wt% respectively. The water contact angle (25.91°-80.23°) and interface adsorption capacity of CNC/G were improved due to hydrophobic group exposure of gelatin. When gelatin concentration exceeded 0.10 % at a fixed oil phase volume fraction (75 %), a high internal phase emulsion (HIPE) stabilized by CNC/G can be formed with a good storage stability. The rheological and microstructure results of HIPE confirmed that low gelatin concentration can assist CNC to form stable emulsion structure. Especially, the auxiliary stabilization mechanism of various gelatin concentration was different. CNC/G-0.10 % and CNC/G-0.15 % stabilized HIPE mainly depended on the enhanced interface adsorption and network structure, while CNC/G-0.20 % stabilized HIPE mainly relied on enhanced interface adsorption/accumulation due to weak electrostatic repulsion and aggregate granular morphology of CNC/G-0.20 %.

VENet: Variational energy network for gland segmentation of pathological images and early gastric cancer diagnosis of whole slide images.

BACKGROUND AND OBJECTIVE: Gland segmentation of pathological images is an essential but challenging step for adenocarcinoma diagnosis. Although deep learning methods have recently made tremendous progress in gland segmentation, they have not given satisfactory boundary and region segmentation results of adjacent glands. These glands usually have a large difference in glandular appearance, and the statistical distribution between the training and test sets in deep learning is inconsistent. These problems make networks not generalize well in the test dataset, bringing difficulties to gland segmentation and early cancer diagnosis. METHODS: To address these problems, we propose a Variational Energy Network named VENet with a traditional variational energy Lv loss for gland segmentation of pathological images and early gastric cancer detection in whole slide images (WSIs). It effectively integrates the variational mathematical model and the data-adaptability of deep learning methods to balance boundary and region segmentation. Furthermore, it can effectively segment and classify glands in large-size WSIs with reliable nucleus width and nucleus-to-cytoplasm ratio features. RESULTS: The VENet was evaluated on the 2015 MICCAI Gland Segmentation challenge (GlaS) dataset, the Colorectal Adenocarcinoma Glands (CRAG) dataset, and the self-collected Nanfang Hospital dataset. Compared with state-of-the-art methods, our method achieved excellent performance for GlaS Test A (object dice 0.9562, object F1 0.9271, object Hausdorff distance 73.13), GlaS Test B (object dice 94.95, object F1 95.60, object Hausdorff distance 59.63), and CRAG (object dice 95.08, object F1 92.94, object Hausdorff distance 28.01). For the Nanfang Hospital dataset, our method achieved a kappa of 0.78, an accuracy of 0.9, a sensitivity of 0.98, and a specificity of 0.80 on the classification task of test 69 WSIs. CONCLUSIONS: The experimental results show that the proposed model accurately predicts boundaries and outperforms state-of-the-art methods. It can be applied to the early diagnosis of gastric cancer by detecting regions of high-grade gastric intraepithelial neoplasia in WSI, which can assist pathologists in analyzing large WSI and making accurate diagnostic decisions.

Expression landscape of cancer-FOXP3 and its prognostic value in pancreatic adenocarcinoma.

FOXP3, a key identifier of Treg, has also been identified in tumor cells, which is referred to as cancer-FOXP3 (c-FOXP3). Human c-FOXP3 undergoes multiple alternative splicing events, generating several isoforms, like c-FOXP3FL and c-FOXP3Δ3. Previous research on c-FOXP3 often ignore its cellular source (immune or tumor cells) and isoform expression patterns, which may obscure our understanding of its clinical significance. Our immunohistochemistry investigations which conducted across 18 tumors using validated c-FOXP3 antibodies revealed distinct expression landscapes for c-FOXP3 and its variants, with the majority of tumors exhibited a predominantly expression of c-FOXP3Δ3. In pancreatic ductal adenocarcinoma (PDAC), we further discovered a potential link between nuclear c-FOXP3Δ3 in tumor cells and poor prognosis. Overexpression of c-FOXP3Δ3 in tumor cells was associated with metastasis. This work elucidates the expression pattern of c-FOXP3 in pan-cancer and indicates its potential as a prognostic biomarker in clinical settings, offering new perspectives for its clinical application.

TSPAN8+ myofibroblastic cancer-associated fibroblasts promote chemoresistance in patients with breast cancer.

Cancer-associated fibroblasts (CAFs) are abundant stromal cells in the tumor microenvironment that promote cancer progression and relapse. However, the heterogeneity and regulatory roles of CAFs underlying chemoresistance remain largely unclear. Here, we performed a single-cell analysis using high-dimensional flow cytometry analysis and identified a distinct senescence-like tetraspanin-8 (TSPAN8)+ myofibroblastic CAF (myCAF) subset, which is correlated with therapeutic resistance and poor survival in multiple cohorts of patients with breast cancer (BC). TSPAN8+ myCAFs potentiate the stemness of the surrounding BC cells through secretion of senescence-associated secretory phenotype (SASP)-related factors IL-6 and IL-8 to counteract chemotherapy. NAD-dependent protein deacetylase sirtuin 6 (SIRT6) reduction was responsible for the senescence-like phenotype and tumor-promoting role of TSPAN8+ myCAFs. Mechanistically, TSPAN8 promoted the phosphorylation of ubiquitin E3 ligase retinoblastoma binding protein 6 (RBBP6) at Ser772 by recruiting MAPK11, thereby inducing SIRT6 protein destruction. In turn, SIRT6 down-regulation up-regulated GLS1 and PYCR1, which caused TSPAN8+ myCAFs to secrete aspartate and proline, and therefore proved a nutritional niche to support BC outgrowth. By demonstrating that TSPAN8+SIRT6low myCAFs were tightly associated with unfavorable disease outcomes, we proposed that the combined regimen of anti-TSPAN8 antibody and SIRT6 activator MDL-800 is a promising approach to overcome chemoresistance. These findings highlight that senescence contributes to CAF heterogeneity and chemoresistance and suggest that targeting TSPAN8+ myCAFs is a promising approach to circumvent chemoresistance.

The combination of high temperature and Vibrio infection worsens summer mortality in the clam Meretrix petechialis by increasing apoptosis and oxidative stress.

The interaction between environmental factors and Vibrio in bivalves is not well understood, despite the widely held belief that pathogen infection and seawater temperature significantly impact summer mortality. In the present study, we conducted simulated experiments to explore the effects of high temperature and Vibrio infection on the clam Meretrix petechialis. The survival curve analysis revealed that the combined challenge of high temperature and Vibrio infection (31°C-vibrio) led to significantly higher clam mortality compared to the groups exposed solely to Vibrio (27°C-vibrio), high temperature (31°C-control), and the control condition (27°C-control). Furthermore, PCoA analysis of 11 immune genes indicated that Vibrio infection predominated during the incubation period, with a gradual equilibrium between these factors emerging during the course of the infection. Additionally, our investigations into apoptosis and autophagy processes exhibited significant induction of mTOR and Bcl2 of the 31°C-vibrio group in the early challenge stage, followed by inhibition in the later stage. Oxidative stress analysis demonstrated a substantial additive effect on malondialdehyde (MDA) and glutathione (GSH) content in the combined challenge group compared to the control group. Comparative transcriptome analysis revealed a significant increase in differentially expressed genes related to immunity, such as complement C1q-like protein, C-type lectin, big defensin, and lysozyme, in the 31°C-vibrio group, suggesting that the synergistic effect of high temperature and Vibrio infection triggers more robust antibacterial immune responses. These findings provide critical insights for understanding the infection process and uncovering the causes of summer mortality.

A new medical device applied in a case of acute fecal impaction with overflow diarrhea: a case report.

BACKGROUND: Fecal impaction is a digestive system disease, that is most common in the elderly population and becomes more prevalent with increasing age. Manual removal can successfully remove the impaction in 80% of fecal impaction cases. In severe cases, endoscopy and surgery may be necessary. CASE PRESENTATION: A 78-year-old Han Chinese man living in a nursing home was diagnosed with fecal impaction; his initial symptom was overflow diarrhea, which is a rare occurrence with regard to fecal impaction. Nevertheless, we were able to effectively treat this situation by employing a new medical device that presents a novel method for addressing fecal impaction. CONCLUSION: Early identification of fecal impaction with atypical symptoms is crucial to provide proper emergency management. A safe and noninvasive treatment method, especially for elderly patients with fecal impaction, should be chosen.

FDA compound library screening Baicalin upregulates TREM2 for the treatment of cerebral ischemia-reperfusion injury.

Acute ischemic stroke (AIS) is a leading cause of global incidence and mortality rates. Oxidative stress and inflammation are key factors in the pathogenesis of AIS neuroinjury. Therefore, it is necessary to develop drugs that target neuroinflammation and oxidative stress in AIS. The Triggering Receptor Expressed on Myeloid Cells 2 (TREM2), primarily expressed on microglial cell membranes, plays a critical role in reducing inflammation and oxidative stress in AIS. In this study, we employed a high-throughput screening (HTS) strategy to evaluate 2625 compounds from the (Food and Drug Administration) FDA library in vitro to identify compounds that upregulate the TREM2 receptor on microglia. Through this screening, we identified Baicalin as a potential drug for AIS treatment. Baicalin, a flavonoid compound extracted and isolated from the root of Scutellaria baicalensis, demonstrated promising results. Next, we established an in vivo mouse model of cerebral ischemia-reperfusion injury (MCAO/R) and an in vitro microglia cell of oxygen-glucose deprivation reperfusion (OGD/R) to investigate the role of Baicalin in inflammation injury, oxidative stress, and neuronal apoptosis. Our results showed that baicalin effectively inhibited microglia activation, reactive oxygen species (ROS) production, and inflammatory responses in vitro. Additionally, baicalin suppressed neuronal cell apoptosis. In the in vivo experiments, baicalin not only improved neurological functional deficits and reduced infarct volume but also inhibited microglia activation and inflammatory responses. Overall, our findings demonstrate the efficacy of Baicalin in treating MCAO/R by upregulating TREM2 to reduce inflammatory responses and inhibit neuronal apoptosis.

Integrated transcriptomic and metabolomic analyses reveals anthocyanin biosynthesis in leaf coloration of quinoa (Chenopodium quinoa Willd.).

BACKGROUND: Quinoa leaves demonstrate a diverse array of colors, offering a potential enhancement to landscape aesthetics and the development of leisure-oriented sightseeing agriculture in semi-arid regions. This study utilized integrated transcriptomic and metabolomic analyses to investigate the mechanisms underlying anthocyanin synthesis in both emerald green and pink quinoa leaves. RESULTS: Integrated transcriptomic and metabolomic analyses indicated that both flavonoid biosynthesis pathway (ko00941) and anthocyanin biosynthesis pathway (ko00942) were significantly associated with anthocyanin biosynthesis. Differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) were analyzed between the two germplasms during different developmental periods. Ten DEGs were verified using qRT-PCR, and the results were consistent with those of the transcriptomic sequencing. The elevated expression of phenylalanine ammonia-lyase (PAL), chalcone synthase (CHS), 4-coumarate CoA ligase (4CL) and Hydroxycinnamoyltransferase (HCT), as well as the reduced expression of flavanone 3-hydroxylase (F3H) and Flavonol synthase (FLS), likely cause pink leaf formation. In addition, bHLH14, WRKY46, and TGA indirectly affected the activities of CHS and 4CL, collectively regulating the levels of cyanidin 3-O-(3'', 6''-O-dimalonyl) glucoside and naringenin. The diminished expression of PAL, 4CL, and HCT decreased the formation of cyanidin-3-O-(6"-O-malonyl-2"-O-glucuronyl) glucoside, leading to the emergence of emerald green leaves. Moreover, the lowered expression of TGA and WRKY46 indirectly regulated 4CL activity, serving as another important factor in maintaining the emerald green hue in leaves N1, N2, and N3. CONCLUSION: These findings establish a foundation for elucidating the molecular regulatory mechanisms governing anthocyanin biosynthesis in quinoa leaves, and also provide some theoretical basis for the development of leisure and sightseeing agriculture.

Comprehensive Multi-omics Approaches Provide Insights to Summer Mortality in the Clam Meretrix petechialis.

Bivalve mass mortalities have been reported worldwide, which not only can be explained as a result of pathogen infection, but may reflect changes in environments. Although these episodes were often reported, there was limited information concerning the molecular responses to various stressors leading to summer mortality. In the present work, RNA sequencing (RNA-seq), tandem mass tagging (TMT)-based quantitative proteomics, and 16S rRNA sequencing were used to explore the natural outbreak of summer mortality in the clam Meretrix petechialis. We identified a total of 172 differentially expressed genes (DEGs) and 222 differentially expressed proteins (DEPs) in the diseased group compared to the normal group. The inconsistent expression profiles of immune DEGs/DEPs may be due to the immune dysregulation of the diseased clams. Notably, 11 solute carrier family genes were found among the top 20 down-regulated genes in the diseased group, indicating that weakened transmembrane transport ability might occur in the diseased clams. Integration analysis of transcriptomic and proteomic results showed that many metabolic processes such as "arginine and proline metabolism" and "tyrosine metabolism" were inhibited in the diseased group, suggesting metabolic inhibition. Moreover, 16S rRNA sequencing revealed that the microbial composition of clam hepatopancreas was disordered in the diseased group. The comparison of DEGs expression between the natural summer mortality event and an artificial challenge experiment involving both Vibrio infection and heat stress revealed 9/15 genes showing similar expression trends between the two conditions, suggesting that the summer mortality might be caused by a combination of high temperature and Vibrio infection. These results would deepen our understanding of summer mortality and provide candidate resistance markers for clam resistance breeding.

Transcriptomic insights into vibrio-induced mortality in the clam Meretrix petechialis under high temperature.

In this study, we investigate the mortality of the clam Meretrix petechialis facing a vibrio challenge under different temperatures and the underlying molecular mechanisms. Our experiment distinctly revealed that clam mortality was predominantly observed under high temperature, highlighting the critical impact of thermal stress on clam susceptibility to infection. Using RNA-seq, we further compared the global transcriptional response to vibrio in clam gills between high and low temperatures. Compared to other groups, the differentially expressed genes in vibrio-challenged group at high temperature associated with immunity, oxidative stress, and membrane transport. Key results show a weakened immune response in clams at high temperature, especially in the TNF signaling pathway, and a decrease in membrane transport efficiency, notably in SLC proteins. Additionally, high temperature enhanced pro-inflammatory related unsaturated fatty acid metabolism, leading to increased oxidative damage. This was further evidenced by our biochemical assays, which showed significantly higher levels of lipid peroxidation and protein carbonylation in clams at high temperature, indicating heightened oxidative damage. RT-PCR validation of selected DEGs corroborated the RNA-seq findings. Our findings contribute to the understanding of more frequent shellfish mortality in summer, emphasizing the role of temperature in pathogen response, elucidating the molecular mechanisms underlying the synergistic effect of pathogen and high temperature stresses. The key genes identified provide potential targets for resistance-assisted breeding. This research has significant implications for bivalve aquaculture and their physiology, particularly in light of global climate changes affecting marine ecosystems.