Small molecule activators of TAK1 promotes its activity-dependent ubiquitination and TRAIL-mediated tumor cell death.

TAK1 is a key modulator of both NF-κB signaling and RIPK1. In TNF signaling pathway, activation of TAK1 directly mediates the phosphorylation of IKK complex and RIPK1. In a search for small molecule activators of RIPK1-mediated necroptosis, we found R406/R788, two small molecule analogs that could promote sustained activation of TAK1. Treatment with R406 sensitized cells to TNF-mediated necroptosis and RIPK1-dependent apoptosis by promoting sustained RIPK1 activation. Using click chemistry and multiple biochemical binding assays, we showed that treatment with R406 promotes the activation of TAK1 by directly binding to TAK1, independent of its original target Syk kinase. Treatment with R406 promoted the ubiquitination of TAK1 and the interaction of activated TAK1 with ubiquitinated RIPK1. Finally, we showed that R406/R788 could promote the cancer-killing activities of TRAIL in vitro and in mouse models. Our studies demonstrate the possibility of developing small molecule TAK1 activators to potentiate the effect of TRAIL as anticancer therapies.

CsPAT1, a GRAS transcription factor, promotes lignin accumulation by antagonistic interacting with CsWRKY13 in tea plants.

Lignin is an important component of plant cell walls and plays crucial roles in the essential agronomic traits of tea quality and tenderness. However, the molecular mechanisms underlying the regulation of lignin biosynthesis in tea plants remain unclear. CsWRKY13 acts as a negative regulator of lignin biosynthesis in tea plants. In this study, we identified a GRAS transcription factor, phytochrome A signal transduction 1 (CsPAT1), that interacts with CsWRKY13. Silencing CsPAT1 expression in tea plants and heterologous overexpression in Arabidopsis demonstrated that CsPAT1 positively regulates lignin accumulation. Further investigation revealed that CsWRKY13 directly binds to the promoters of CsPAL and CsC4H and suppresses transcription of CsPAL and CsC4H. CsPAT1 indirectly affects the promoter activities of CsPAL and CsC4H by interacting with CsWRKY13, thereby facilitating lignin biosynthesis in tea plants. Compared with the expression of CsWRKY13 alone, the co-expression of CsPAT1 and CsWRKY13 in Oryza sativa significantly increased lignin biosynthesis. Conversely, compared with the expression of CsPAT1 alone, the co-expression of CsPAT1 and CsWRKY13 in O. sativa significantly reduced lignin accumulation. These results demonstrated the antagonistic regulation of the lignin biosynthesis pathway by CsPAT1 and CsWRKY13. These findings improve our understanding of lignin biosynthesis mechanisms in tea plants and provide insights into the role of the GRAS transcription factor family in lignin accumulation.

Integrative analysis reveals structural basis for transcription activation of Nurr1 and Nurr1-RXRα heterodimer.

Orphan nuclear receptor Nurr1 plays important roles in the progression of various diseases, including Parkinson's disease, neuroinflammation, Alzheimer's disease, and multiple sclerosis. It can recognize DNA as a monomer or heterodimer with retinoid X receptor α (RXRα). But the molecular mechanism of its transcriptional activity regulation is still largely unknown. Here we obtained a crystal structure of monomer Nurr1 (DNA- and ligand-binding domains, DBD and LBD) bound to NGFI-B response element. The structure exhibited two different forms with distinct DBD orientations, unveiling the conformational flexibility of nuclear receptor monomer. We then generated an integrative model of Nurr1-RXRα heterodimer. In the context of heterodimer, the structural flexibility of Nurr1 would contribute to its transcriptional activity modulation. We demonstrated that the DNA sequence may specifically modulate the transcriptional activity of Nurr1 in the absence of RXRα agonist, but the modulation can be superseded when the agonist binds to RXRα. Together, we propose a set of signaling pathways for the constitutive transcriptional activation of Nurr1 and provide molecular mechanisms for therapeutic discovery targeting Nurr1 and Nurr1-RXRα heterodimer.

Simplified Helicobacter pylori therapy for patients with penicillin allergy: a randomised controlled trial of vonoprazan-tetracycline dual therapy.

BACKGROUND AND AIMS: This study aimed to evaluate the efficacy and safety of vonoprazan and tetracycline (VT) dual therapy as first-line treatment for Helicobacter pylori infection in patients with penicillin allergy. METHODS: In this randomised controlled trial, treatment-naïve adults with H. pylori infection and penicillin allergy were randomised 1:1 to receive either open-label VT dual therapy (vonoprazan 20 mg two times per day+tetracycline 500 mg three times a day) or bismuth quadruple therapy (BQT; lansoprazole 30 mg two times per day+colloidal bismuth 150 mg three times a day+tetracycline 500 mg three times a day+metronidazole 400 mg three times a day) for 14 days. The primary outcome was non-inferiority in eradication rates in the VT dual group compared with the BQT group. Secondary outcomes included assessing adverse effects. RESULTS: 300 patients were randomised. The eradication rates in the VT group and the BQT group were: 92.0% (138/150, 95% CI 86.1% to 95.6%) and 89.3% (134/150, 95% CI 83.0% to 93.6%) in intention-to-treat analysis (difference 2.7%; 95% CI -4.6% to 10.0%; non-inferiority p=0.000); 94.5% (138/146, 95% CI 89.1% to 97.4%) and 93.1% (134/144, 95% CI 87.3% to 96.4%) in modified intention-to-treat analysis (difference 1.5%; 95% CI -4.9% to 8.0%; non-inferiority p=0.001); 95.1% (135/142, 95% CI 89.7% to 97.8%) and 97.7% (128/131, 95% CI 92.9% to 99.4%) in per-protocol analysis (difference 2.6%; 95% CI -2.9% to 8.3%; non-inferiority p=0.000). The treatment-emergent adverse events (TEAEs) were significantly lower in the VT group (14.0% vs 48.0%, p=0.000), with fewer treatment discontinuations due to TEAEs (2.0% vs 8.7%, p=0.010). CONCLUSIONS: VT dual therapy demonstrated efficacy and safety as a first-line treatment for H. pylori infection in the penicillin-allergic population, with comparable efficacy and a lower incidence of TEAEs compared with traditional BQT. TRIAL REGISTRATION NUMBER: ChiCTR2300074693.

Circadian rhythm response and its effect on photosynthetic characteristics of the Lhcb family genes in tea plant.

BACKGROUND: The circadian clock, also known as the circadian rhythm, is responsible for predicting daily and seasonal changes in the environment, and adjusting various physiological and developmental processes to the appropriate times during plant growth and development. The circadian clock controls the expression of the Lhcb gene, which encodes the chlorophyll a/b binding protein. However, the roles of the Lhcb gene in tea plant remain unclear. RESULTS: In this study, a total of 16 CsLhcb genes were identified based on the tea plant genome, which were distributed on 8 chromosomes of the tea plant. The promoter regions of CsLhcb genes have a variety of cis-acting elements including hormonal, abiotic stress responses and light response elements. The CsLhcb family genes are involved in the light response process in tea plant. The photosynthetic parameter of tea leaves showed rhythmic changes during the two photoperiod periods (48 h). Stomata are basically open during the day and closed at night. Real-time quantitative PCR results showed that most of the CsLhcb family genes were highly expressed during the day, but were less expressed at night. CONCLUSIONS: Results indicated that CsLhcb genes were involved in the circadian clock process of tea plant, it also provided potential references for further understanding of the function of CsLhcb gene family in tea plant.

The association of triglyceride-glucose-waist circumference with metabolic associated fatty liver disease and the severity of liver steatosis and fibrosis in American adults: a population-based study.

BACKGROUND: The global obesity pandemic has led to an alarming rise in the prevalence of metabolic-associated fatty liver disease (MAFLD), making it a substantial clinical and economic burden on society. Early detection and effective treatment of MAFLD are imperative to mitigate its impact. METHODS: This cross-sectional study was conducted involving 4634 adults from the National Health and Nutrition Examination Surveys (NHANES) 2017-2018 cycle. Transient elastography (TE) was used to diagnose MAFLD and assess the extent of liver steatosis and fibrosis. Multivariate logistic regression models were utilized to examine the association between the triglyceride and glucose index-waist circumference (TyG-WC) and the risk of MAFLD, liver fibrosis, and steatosis. RESULTS: A positive association between TyG-WC and MAFLD persisted across all three models: model1: OR = 8.44, 95% CI: 6.85-10.38 (unadjusted), model2: OR = 8.28, 95% CI: 6.53-10.50 (partially adjusted), and model3: OR = 7.98, 95% CI: 4.11-15.46 (fully adjusted). Further investigation through interaction and stratified analysis revealed that this association was more pronounced in the non-obese and Non-Hispanic White persons groups. Moreover, a non-linear relationship analysis unveiled threshold and saturation effects between TyG-WC and MAFLD. Specifically, a TyG-WC value of approximately 600 may represent the threshold effect for MAFLD risk, while 1200 may signify the saturation effect of MAFLD risk. Finally, a robust correlation between TyG-WC and the severity of liver steatosis and fibrosis was found. CONCLUSIONS: The findings suggest that the TyG-WC index exhibits excellent predictive value for MAFLD in the general American population.

Sex-specific grey matter abnormalities in individuals with chronic insomnia.

Previous studies have reported sex differences in altered brain function in patients with chronic insomnia (CI). However, sex-related alterations in brain morphology have rarely been investigated. This study aimed to investigate sex-specific grey matter (GM) alterations in patients with CI and to examine the relationship between GM alterations and neuropsychological assessments. Ninety-three (65 females and 28 males) patients and 78 healthy (50 females and 28 males) controls were recruited. Structural magnetic resonance imaging data were analysed using voxel-based morphometry to test for interactions between sex and diagnosis. Spearman's correlation was used to assess the associations among structure, disease duration, and sleep-, mood-, and cognition-related assessments. Males with CI showed reduced GM volume in the left inferior parietal lobe, left middle cingulate cortex, and right supramarginal gyrus. Females with CI showed increased GM volume in the right Rolandic operculum. Moreover, mood-related assessments were negatively correlated with GM volumes in the right supramarginal gyrus and left inferior parietal lobe in the male patients, and cognitive-related assessments were positively correlated with GM volumes in the Rolandic operculum in the female patients. Our findings indicate sex-specific alterations in brain morphology in CI, thereby broadening our understanding of sex differences in CI and potentially providing complementary evidence for the development of more effective therapies and individual treatments.

Collapse of complexity of brain and body activity due to excessive inhibition and MeCP2 disruption.

Complex body movements require complex dynamics and coordination among neurons in motor cortex. Conversely, a long-standing theoretical notion supposes that if many neurons in motor cortex become excessively synchronized, they may lack the necessary complexity for healthy motor coding. However, direct experimental support for this idea is rare and underlying mechanisms are unclear. Here we recorded three-dimensional body movements and spiking activity of many single neurons in motor cortex of rats with enhanced synaptic inhibition and a transgenic rat model of Rett syndrome (RTT). For both cases, we found a collapse of complexity in the motor system. Reduced complexity was apparent in lower-dimensional, stereotyped brain-body interactions, neural synchrony, and simpler behavior. Our results demonstrate how imbalanced inhibition can cause excessive synchrony among movement-related neurons and, consequently, a stereotyped motor code. Excessive inhibition and synchrony may underlie abnormal motor function in RTT.

Interleukin-37 relieves PM2.5-triggered lung injury by inhibiting autophagy through the AKT/mTOR signaling pathway in vivo and in vitro.

Autophagy mediates PM2.5-related lung injury (LI) and is tightly linked to inflammation and apoptosis processes. IL-37 has been demonstrated to regulate autophagy. This research aimed to examine the involvement of IL-37 in the progression of PM2.5-related LI and assess whether autophagy serves as a mediator for its effects.To create a model of PM2.5-related LI, this research employed a nose-only PM2.5 exposure system and utilized both human IL-37 transgenic mice and wild-type mice. The hIL-37tg mice demonstrated remarkable reductions in pulmonary inflammation and pathological LI compared to the WT mice. Additionally, they exhibited activation of the AKT/mTOR signaling pathway, which served to regulate the levels of autophagy and apoptosis.Furthermore, in vitro experiments revealed a dose-dependent upregulation of autophagy and apoptotic proteins following exposure to PM2.5 DMSO extraction. Simultaneously, p-AKT and p-mTOR expression was found to decrease. However, pretreatment with IL-37 demonstrated a remarkable reduction in the levels of autophagy and apoptotic proteins, along with an elevation of p-AKT and p-mTOR. Interestingly, pretreatment with rapamycin, an autophagy inducer, weakened the therapeutic impact of IL-37. Conversely, the therapeutic impact of IL-37 was enhanced when treated with 3-MA, a potent autophagy inhibitor. Moreover, the inhibitory effect of IL-37 on autophagy was successfully reversed by administering AKT inhibitor MK2206. The findings suggest that IL-37 can inhibit both the inflammatory response and autophagy, leading to the alleviation of PM2.5-related LI. At the molecular level, IL-37 may exert its anti autophagy and anti apoptosis effects by activating the AKT/mTOR signaling pathway.

Medical education challenges in Mainland China: An analysis of the application of problem-based learning.

BACKGROUND: The medical education system in mainland China faces numerous challenges and the lack of learner-centered approaches may contribute to passive learning and reduced student engagement. While problem-based learning (PBL) is common in Western medical schools, its feasibility in China is questioned due to cultural differences. This systematic review aims to summarize the application of PBL in medical education in mainland China based on existing literature, as well as to identify the challenges and opportunities encountered in its implementation. METHODS: A systematic literature review was conducted using electronic databases, including MEDLINE, Cochrane Library, EMBASE, Web of Science, Wan fang and CNKI databases. Grey literature sources were explored using Google Scholar. The search was limited to articles that include at least one English abstract up to May 1st, 2023. The inclusion criteria were studies that reported the use of PBL in medical education in mainland China. RESULTS: A total of 21 articles were included in the final analysis. The findings indicate that PBL is a well-adopted and effective learning method in most medical education, especially for developing critical thinking, problem-solving, and teamwork skills. However, the application of PBL in mainland China is limited due to various challenges, including faculty resistance, inadequate resources and cultural barriers. To effectively address these challenges, it is essential to provide faculty training, develop appropriate assessment methods to evaluate student progress within the PBL framework and create conducive spaces and resources that support collaborative learning and critical thinking. CONCLUSION: The utilization of PBL in mainland China holds potential for enhancing medical education. However, its successful implementation requires significant efforts to address the identified challenges. It is crucial to engage stakeholders in a collaborative effort to promote the application of PBL and ultimately improve the quality of medical education in mainland China.

Hypolipidemic Effects of Mesona chinensis Benth Polysaccharides with Different Structures and Molecular Weights.

Four novel Mesona chinensis Benth polysaccharides were isolated using aqueous alcohol precipitation. Their molecular weights were determined using high-performance gel permeation chromatography: MA1 (2.3 kDa), MA2 (80.5 kDa), MA3 (180.9 kDa), and MA4 (635.2 kDa), and their compositions were analyzed using GC-MS. The polysaccharides were mainly D-glucose, D-galactose, L-Rhamnose, D-arabinose, D-xylose, and D-mannose. The structural characteristics were further analyzed using infrared spectrophotometry and were identified as a type of pyrrhic sugar. An insulin-induced insulin resistance model of HepG2 cells and oleic acid-induced fat accumulation model of insulin were established to evaluate the hypolipidemic effects. Three Bacteroides spp. [Bacteroides thetaiotaomicron (BT), B. ovatus (BO), and B. cellulosilyticus (BC)] that were negatively correlated with lipid-lowering activity were used to evaluate the lipid-lowering activity of polysaccharides. The Bacteroides metabolites of MA1 and MA2 exhibited hypolipidemic effects and antioxidant activities and could potentially be used as lipid-lowering supplements.

Cadmium Exposure in Male Rats Results in Ovarian Granulosa Cell Apoptosis in Female Offspring and Paternal Genetic Effects.

The aim of this study was to investigate whether the damage to male offspring induced by cadmium (Cd) exposure during embryonic period leads to the apoptosis of ovarian granulosa cells (OGCs) in the next generation of female offspring, and whether this apoptosis in the offspring was due to paternal genetic effects. Pregnant Sprague-Dawley (SD) rats were exposed to CdCl2 (0, 0.5, 2.0, or 8.0 mg/kg) by gavage daily for 20 days to produce the filial 1 (F1) generation. F1 males were mated with newly purchased females to produce the F2 generation, and the F3 generation was generated in the same way. No apoptotic bodies were observed in the OGCs of either the F2 or F3 generation as shown by electron microscopy, and a reduced OGC apoptosis rate (detected by flow cytometry) was observed in F2 OGCs from the Cd-exposed group. Moreover, the mRNA (qRT-PCR) levels of Bax and Bcl-2 and the protein (western blotting) level of pro-caspase-8 increased in the F2 generation (p < 0.05). The expression of apoptosis-related miRNAs (qRT-PCR) and methylation of apoptosis-related genes (determined via bisulfite-sequencing PCR) in OGCs were further determined. Compared with those of the controls, the expression patterns of microRNAs (miRNAs) in the F2 offspring were different in the Cd-exposed group. The miR-92a-2-5p expression levels were decreased in both the F2 and F3 generations (p < 0.05), while the average methylation level of apoptosis-related genes did not change significantly (except for individual loci). In summary, this study showed that the paternal genetic intergenerational effect of male Cd exposure during embryonic period induced apoptosis of OGCs in the offspring was weakened, and the transgenerational effect disappeared; nevertheless, intergenerational and transgenerational changes in apoptosis-related genes, epigenetic modifications, DNA methylation, and miRNAs were observed, and may be important for understanding the homeostatic mechanisms of the body to alleviate the intergenerational transmission of Cd-induced damage.

A highly sensitive point-of-care detection platform for Salmonella typhimurium by integrating magnetic enrichment and fluorescent CsPbBr3@SiO2.

A platform was designed based on Fe3O4 and CsPbBr3@SiO2 for integrated magnetic enrichment-fluorescence detection of Salmonella typhimurium, which significantly simplifies the detection process and enhances the working efficiency. Fe3O4 served as a magnetic enrichment unit for the capture of S. typhimurium. CsPbBr3@SiO2 was employed as a fluorescence-sensing unit for quantitative signal output, where SiO2 was introduced to strengthen the stability of CsPbBr3, improve its biomodificability, and prevent lead leakage. More importantly, the SiO2 shell shows neglectable absorption or scattering towards fluorescence, making the CsPbBr3@SiO2 exhibit a high quantum yield of 74.4%. After magnetic enrichment, the decreasing rate of the fluorescence emission intensity of the CsPbBr3@SiO2 supernatant at 527 nm under excitation light at UV 365 nm showed a strong linear correlation with S. typhimurium concentration of 1 × 102~1 × 108 CFU∙mL-1, and the limit of detection (LOD) reached 12.72 CFU∙mL-1. This platform has demonstrated outstanding stability, reproducibility, and resistance to interference, which provides an alternative for convenient and quantitative detection of S. typhimurium.

The Role of ACE2 in Neurological Disorders: From Underlying Mechanisms to the Neurological Impact of COVID-19.

Angiotensin-converting enzyme 2 (ACE2) has become a hot topic in neuroscience research in recent years, especially in the context of the global COVID-19 pandemic, where its role in neurological diseases has received widespread attention. ACE2, as a multifunctional metalloprotease, not only plays a critical role in the cardiovascular system but also plays an important role in the protection, development, and inflammation regulation of the nervous system. The COVID-19 pandemic further highlights the importance of ACE2 in the nervous system. SARS-CoV-2 enters host cells by binding to ACE2, which may directly or indirectly affect the nervous system, leading to a range of neurological symptoms. This review aims to explore the function of ACE2 in the nervous system as well as its potential impact and therapeutic potential in various neurological diseases, providing a new perspective for the treatment of neurological disorders.

Genome-Wide Identification of CHYR Gene Family in Sophora alopecuroides and Functional Analysis of SaCHYR4 in Response to Abiotic Stress.

Sophora alopecuroides has important uses in medicine, wind breaking, and sand fixation. The CHY-zinc-finger and RING-finger (CHYR) proteins are crucial for plant growth, development, and environmental adaptation; however, genetic data regarding the CHYR family remain scarce. We aimed to investigate the CHYR gene family in S. alopecuroides and its response to abiotic stress, and identified 18 new SaCHYR genes from S. alopecuroides whole-genome data, categorized into 3 subclasses through a phylogenetic analysis. Gene structure, protein domains, and conserved motifs analyses revealed an exon-intron structure and conserved domain similarities. A chromosome localization analysis showed distribution across 12 chromosomes. A promoter analysis revealed abiotic stress-, light-, and hormone-responsive elements. An RNA-sequencing expression pattern analysis revealed positive responses of SaCHYR genes to salt, alkali, and drought stress. SaCHYR4 overexpression considerably enhanced alkali and drought tolerance in Arabidopsis thaliana. These findings shed light on SaCHYR's function and the resistance mechanisms of S. alopecuroides, presenting new genetic resources for crop resistance breeding.

Efficacy of Agricultural Residue-Derived Biochar for Tackling Cadmium Contamination in an Aqueous Solution.

This study aimed to investigate the efficacy of biochar, produced from different agricultural residues varying in lignin and cellulose content and subjected to different pyrolysis temperatures, in removing cadmium ions (Cd (II)) from an aqueous solution. This removal process is crucial for protecting human health and the environment. Specifically, the study focused on the adsorption behaviors of Cd (II) by the biochars made from rice husk biochar (RHB), maize straw biochar (MSB), peanut shell biochar (PSB), cottonseed shell biochar (CHB), and mulberry leaf biochar (MLB), which were prepared at 300 °C and 600 °C. The results indicated that the type of agricultural residue used to produce biochar significantly influenced the adsorption of Cd (II). Notably, mulberry leaf biochar prepared at 300 °C (MLB-300) demonstrated the highest adsorption efficiency, achieving a maximum adsorption capacity of 42.2 mg g-1. Batch adsorption experiments assessed the impact of various factors, including system pH, NO3- concentration, and adsorption duration. The adsorption kinetics were better described by the pseudo-second-order model than the pseudo-first-order model. Moreover, the study found that the lignin content of the biochar plays a major role in determining the adsorption capacity. The surface characteristics of biochar, influenced by the types of agricultural residues and preparation temperature, directly impact its adsorption mechanism and capacity. While biochar produced at 300 °C showed optimal Cd(II) adsorption, those processed at 600 °C were less effective, likely due to the loss of functional groups at higher temperatures.

Outcome of chairside CAD/CAM ceramic restorations on endodontically treated posterior teeth: a prospective study.

OBJECTIVE: The aim of this study was to evaluate the outcome and risk factors for chairside CAD/CAM full cusp coverage restorations on endodontically treated posterior teeth after 3 years of follow-up. METHODS: A total of 245 endodontically treated posterior teeth of 224 patients were included and restored with CAD/CAM full cusp coverage all-ceramic restorations according to a standardized protocol. Patients were recalled after treatments 1 to 3 years and underwent clinical and radiological examinations. At recall, modified FDI criteria were used to determine treatment outcomes by 2 evaluators. Success was determined when FDI scores were 1-2, and failure was indicated when FDI scores were 5. Logistic regression analysis was performed to evaluate potential risk factors. RESULTS: A total of 183 patients presented at recall, and the clinical outcomes of 201 teeth were analyzed with a recall rate of 82.0% for teeth and 81.7% for patients after 1-3 years of follow-up.185 of 201 teeth were found to have FDI scores of 1-2, and the success rate was 92%. No teeth were extracted during the follow-up period. Fourteen failed cases with an FDI score of 5 presented restoration dislocation, fracture of restoration or/and tooth. Logistic regression analysis revealed that oral parafunction (OR 2.281, 95% CI 2.2 ~ 47.5, P value 0.01) was a risk factor for success rate. CONCLUSION: Chairside CAD/CAM all-ceramic full cusp coverage restoration was (could be) a promising alternative for restoring endodontically treated posterior teeth.

Astrocyte-to-neuron reprogramming and crosstalk in the treatment of Parkinson's disease.

Parkinson's disease (PD) is currently the fastest growing disabling neurological disorder worldwide, with motor and non-motor symptoms being its main clinical manifestations. The primary pathological features include a reduction in the number of dopaminergic neurons in the substantia nigra and decrease in dopamine levels in the nigrostriatal pathway. Existing treatments only alleviate clinical symptoms and do not stop disease progression; slowing down the loss of dopaminergic neurons and stimulating their regeneration are emerging therapies. Preclinical studies have demonstrated that transplantation of dopamine cells generated from human embryonic or induced pluripotent stem cells can restore the loss of dopamine. However, the application of cell transplantation is limited owing to ethical controversies and the restricted source of cells. Until recently, the reprogramming of astrocytes to replenish lost dopaminergic neurons has provided a promising alternative therapy for PD. In addition, repair of mitochondrial perturbations, clearance of damaged mitochondria in astrocytes, and control of astrocyte inflammation may be extensively neuroprotective and beneficial against chronic neuroinflammation in PD. Therefore, this review primarily focuses on the progress and remaining issues in astrocyte reprogramming using transcription factors (TFs) and miRNAs, as well as exploring possible new targets for treating PD by repairing astrocytic mitochondria and reducing astrocytic inflammation.

Identification of key genes and the pathophysiology associated with allergen-specific immunotherapy for allergic rhinitis.

BACKGROUND: Allergen-specific immunotherapy (AIT) is a causative treatment in allergic rhinitis (AR), comprising long-term allergen administration and over three years of treatment. This study is carried out for revealing the mechanisms and key genes of AIT in AR. METHODS: The present study utilized online Gene Expression Omnibus (GEO) microarray expression profiling dataset GSE37157 and GSE29521 to analyze the hub genes changes related to AIT in AR. Based on limma package, differential expression analysis for the two groups (samples of allergic patients prior to AIT and samples of allergic patients undergoing AIT) was performed to obtain differentially expressed genes (DEGs). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEGs were conducted using DAVID database. A Protein-Protein Interaction network (PPI) was built and a significant network module was acquired by using Cytoscape software (Cytoscape, 3.7.2). Utilizing the miRWalk database, we identified potential gene biomarkers, constructed interaction networks of target genes and microRNAs (miRNAs) using Cytoscape software, and explore the cell type-specific expression patterns of these genes in peripheral blood using publicly available single-cell RNA sequencing data (GSE200107). Finally, we are using PCR to detect changes in the hub genes that are screened using the above method in peripheral blood before and after AIT treatment. RESULTS: GSE37157 and GSE29521 included 28 and 13 samples, respectively. A total of 119 significantly co-upregulated DEGs and 33 co-downregulated DEGs were obtained from two datasets. The GO and KEGG analyses demonstrated that protein transport, positive regulation of apoptotic process, Natural killer cell mediated cytotoxicity, T cell receptor signaling pathway, TNF signaling pathway, B cell receptor signaling pathway and Apoptosis may be potential candidate therapeutic targets for AIT of AR. From the PPI network, 20 hub genes were obtained. Among them, the PPI sub-networks of CASP3, FOXO3, PIK3R1, PIK3R3, ATF4, and POLD3 screened out from our study have been identified as reliable predictors of AIT in AR, especially the PIK3R1. CONCLUSION: Our analysis has identified novel gene signatures, thereby contributing to a more comprehensive understanding of the molecular mechanisms underlying AIT in the treatment of AR.

Single-Probe-Based Colorimetric and Photothermal Dual-Mode Identification of Multiple Bacteria.

Effective identification of multiple pathogenic bacteria in unknown samples is important for disease prevention and control but remains a challenge yet. A single-mode array-based sensing approach is simple and sensitive, but it usually relies on the use of multiple cross-reactive receptors to construct sensor arrays, which is cumbersome and insufficiently accurate. Here, we developed a sensor array with colorimetric and photothermal dual mode of differentiating multiple pathogenic bacteria. The sensor array was based on boronic acid-functionalized Au-Fe3O4 nanoparticles (BA-GMNPs), which not only possess localized surface plasmon resonance properties, showing a burgundy color similar to that of AuNPs, but also exhibit mild superparamagnetism, allowing for the differentiation of bacteria before and after binding to the nanoparticles. Immobilization of BA-GMNPs on the bacterial cell surface by covalent bonding would diminish NaCl-induced assembly of BA-GMNPs. Different BA-GMNPs@bacterial complexes differed in their ability to resist assembly and produced different colorimetric and photothermal response signals. A unique molecular fingerprint of each bacterium was obtained by linear discriminant analysis of the response patterns, demonstrating an effective differentiation among the six species studied. Compared with single-mode sensing arrays based on multiple receptors, this method only requires the preparation of a single nanomaterial, which produces two signal outputs for the identification of multiple bacteria with better differentiation. It can distinguish not only multiple pathogenic bacteria but also Gram-negative and Gram-positive bacteria, and, more importantly, it can perform preliminary discrimination of unknown samples.