Capturing totipotency in human cells through spliceosomal repression.

The cleavage of zygotes generates totipotent blastomeres. In human 8-cell blastomeres, zygotic genome activation (ZGA) occurs to initiate the ontogenesis program. However, capturing and maintaining totipotency in human cells pose significant challenges. Here, we realize culturing human totipotent blastomere-like cells (hTBLCs). We find that splicing inhibition can transiently reprogram human pluripotent stem cells into ZGA-like cells (ZLCs), which subsequently transition into stable hTBLCs after long-term passaging. Distinct from reported 8-cell-like cells (8CLCs), both ZLCs and hTBLCs widely silence pluripotent genes. Interestingly, ZLCs activate a particular group of ZGA-specific genes, and hTBLCs are enriched with pre-ZGA-specific genes. During spontaneous differentiation, hTBLCs re-enter the intermediate ZLC stage and further generate epiblast (EPI)-, primitive endoderm (PrE)-, and trophectoderm (TE)-like lineages, effectively recapitulating human pre-implantation development. Possessing both embryonic and extraembryonic developmental potency, hTBLCs can autonomously generate blastocyst-like structures in vitro without external cell signaling. In summary, our study provides key criteria and insights into human cell totipotency.

The BAG3-IFITM2 Axis Enhances Pancreatic Ductal Adenocarcinoma Growth via the MAPK Signaling Pathway.

Pancreatic ductal adenocarcinoma (PDAC), a highly lethal malignancy, exhibits escalating incidence and mortality rates, underscoring the urgent need for the identification of novel therapeutic targets and strategies. The BAG3 protein, a multifunctional regulator involved in various cellular processes, notably plays a crucial role in promoting tumor progression and acts as a potential "bridge" between tumors and the tumor microenvironment. In this study, we demonstrate that PDAC cells secrete BAG3 (sBAG3), which engages the IFITM2 receptor to activate the MAPK signaling pathway, specifically enhancing pERK activity, thereby propelling PDAC growth. Furthermore, our preliminary investigation into the effects of sBAG3 on co-cultured NK cells intriguingly discovered that sBAG3 diminishes NK cell cytotoxicity and active molecule expression. In conclusion, our findings confirm the pivotal role of the sBAG3-IFITM2 axis in fostering PDAC progression, highlighting the potential significance of sBAG3 as a dual therapeutic target for both tumor and immune cells.

m6A methylation of RNF43 inhibits the progression of endometriosis through regulating oxidative phosphorylation via NDUFS1.

Oxidative phosphorylation is becoming increasingly important in the induction and development of endometriosis. Recently, it has been reported that ring finger protein 43 (RNF43) is involved in the process of oxidative phosphorylation, but the mechanism remains unclear. Our investigation is to delve into the roles of RNF43 in endometriosis and elucidate the related mechanisms. We found RNF43 was downregulated in ectopic endometrial tissue and primary ectopic endometrial stromal cells (ECESCs). Knockdown of RNF43 enhanced cell viability and migration by activating oxidative phosphorylation in eutopic endometrial stromal cells (EUESCs), while overexpression of RNF43 led to the opposite results. Moreover, RNF43 reinforced the ubiquitination and degradation of NADH dehydrogenase Fe-S protein 1 (NDUFS1) by interacting with it. Likewise to RNF43 overexpression, NDUFS1 silencing inhibited cell viability, migration, and oxidative phosphorylation in ECESCs. NDUFS1 was a downstream target of RNF43, mediating its biological role in endometriosis. Interestingly, the expression and stability of RNF43 mRNA were regulated by the Methyltransferase-like 3 (METTL3)/IGF2BP2 m6A modification axis. The results of rat experiments showed decreased RNF43 expression and increased NDUFS1 expression in endometriosis rats, which was enhanced by METTL3 inhibition. Those observations indicated that m6A methylation-mediated RNF43 negatively affects viability and migration of endometrial stromal cells through regulating oxidative phosphorylation via NDUFS1. The discovery of METTL3/RNF43/NDUFS1 axis suggested promising therapeutic targets for endometriosis.

Development of a Novel CD8+ T Cell-Associated Signature for Prognostic Assessment in Hepatocellular Carcinoma.

OBJECTIVE: The aim of this study was to analyze the clinical significance and prognostic value of CD8+ T cell-related regulatory genes in hepatocellular carcinoma (HCC). METHODS: This was a retrospective study. We combined TCGA-LIHC and single-cell RNA sequencing data for Lasso-Cox regression analysis to screen for CD8+ T cell-associated genes to construct a novel signature. The expression of the signature genes was detected at cellular and tissue levels using qRT-PCR, immunohistochemistry, and tissue microarrays. The CIBERSORT algorithm was then used to assess the immune microenvironmental differences between the different risk groups and a drug sensitivity analysis was performed to screen for potential HCC therapeutic agents. RESULTS: An 8-gene CD8 + T cell-associated signature (FABP5, GZMH, ANXA2, KLRB1, CD7, IL7R, BATF, and RGS2) was constructed. Survival analysis showed that high-risk patients had a poorer prognosis in all cohorts. Tumor immune microenvironment analysis revealed 22 immune cell types that differed significantly between patients in different risk groups, with patients in the low-risk group having an immune system that was more active in terms of immune function. Patients in the high-risk group were more prone to immune escape and had a poorer response to immunotherapy, and AZD7762 was screened as the most sensitive drug in the high-risk group. Finally, preliminary experiments have shown that BATF has a promoting effect on the proliferation, migration and invasion of HuH-7 cells. CONCLUSIONS: The CD8+ T-cell-associated signature is expected to be a tool for optimizing individual patient decision-making and monitoring protocols, and to provide new ideas for treatment and prognostic assessment of HCC.

Research Methods and New Advances in Drug-Drug Interactions Mediated by Renal Transporters.

The kidney is critical in the human body's excretion of drugs and their metabolites. Renal transporters participate in actively secreting substances from the proximal tubular cells and reabsorbing them in the distal renal tubules. They can affect the clearance rates (CLr) of drugs and their metabolites, eventually influence the clinical efficiency and side effects of drugs, and may produce drug-drug interactions (DDIs) of clinical significance. Renal transporters and renal transporter-mediated DDIs have also been studied by many researchers. In this article, the main types of in vitro research models used for the study of renal transporter-mediated DDIs are membrane-based assays, cell-based assays, and the renal slice uptake model. In vivo research models include animal experiments, gene knockout animal models, positron emission tomography (PET) technology, and studies on human beings. In addition, in vitro-in vivo extrapolation (IVIVE), ex vivo kidney perfusion (EVKP) models, and, more recently, biomarker methods and in silico models are included. This article reviews the traditional research methods of renal transporter-mediated DDIs, updates the recent progress in the development of the methods, and then classifies and summarizes the advantages and disadvantages of each method. Through the sorting work conducted in this paper, it will be convenient for researchers at different learning stages to choose the best method for their own research based on their own subject's situation when they are going to study DDIs mediated by renal transporters.

Machine Learning Techniques Applied to the Study of Drug Transporters.

With the advancement of computer technology, machine learning-based artificial intelligence technology has been increasingly integrated and applied in the fields of medicine, biology, and pharmacy, thereby facilitating their development. Transporters have important roles in influencing drug resistance, drug-drug interactions, and tissue-specific drug targeting. The investigation of drug transporter substrates and inhibitors is a crucial aspect of pharmaceutical development. However, long duration and high expenses pose significant challenges in the investigation of drug transporters. In this review, we discuss the present situation and challenges encountered in applying machine learning techniques to investigate drug transporters. The transporters involved include ABC transporters (P-gp, BCRP, MRPs, and BSEP) and SLC transporters (OAT, OATP, OCT, MATE1,2-K, and NET). The aim is to offer a point of reference for and assistance with the progression of drug transporter research, as well as the advancement of more efficient computer technology. Machine learning methods are valuable and attractive for helping with the study of drug transporter substrates and inhibitors, but continuous efforts are still needed to develop more accurate and reliable predictive models and to apply them in the screening process of drug development to improve efficiency and success rates.

Hydrogen Sulfide can Scavenge Free Radicals to Improve Spinal Cord Injury by Inhibiting the p38MAPK/mTOR/NF-κB Signaling Pathway.

Spinal cord injury (SCI) causes irreversible cell loss and neurological dysfunctions. Presently, there is no an effective clinical treatment for SCI. It can be the only intervention measure by relieving the symptoms of patients such as pain and fever. Free radical-induced damage is one of the validated mechanisms in the complex secondary injury following primary SCI. Hydrogen sulfide (H2S) as an antioxidant can effectively scavenge free radicals, protect neurons, and improve SCI by inhibiting the p38MAPK/mTOR/NF-κB signaling pathway. In this report, we analyze the pathological mechanism of SCI, the role of free radical-mediated the p38MAPK/mTOR/NF-κB signaling pathway in SCI, and the role of H2S in scavenging free radicals and improving SCI.

Noncovalent interaction network of chalcogen, halogen and hydrogen bonds for supramolecular ß-sheet organization.

An alanine-based bilateral building block, linked by 2,5-thiophenediamide motifs and equipped with C-terminal 4-iodoaniline groups, was designed, allowing a noncovalent interaction network consisting of intramolecular chalcogen bonds and intermolecular halogen/hydrogen bonds, which cooperatively maintain a supramolecular ß-sheet organization in the solid state, as well as in dilute CH3CN solution with a high g factor of -0.017.

Identification, heterologous expression and characterization of a new unspecific peroxygenase from Marasmius fiardii PR-910.

Unspecific peroxygenases (UPOs) are glycosylated enzymes that provide an efficient method for oxyfunctionalizing a variety of substrates using only hydrogen peroxide (H2O2) as the oxygen donor. However, their poor heterologous expression has hindered their practical application. Here, a novel UPO from Marasmius fiardii PR910 (MfiUPO) was identified and heterologously expressed in Pichia pastoris. By employing a two-copy expression cassette, the protein titer reached 1.18 g L-1 in a 5 L bioreactor, marking the highest record. The glycoprotein rMfiUPO exhibited a smeared band in the 40 to 55 kDa range and demonstrated hydroxylation, epoxidation and alcohol oxidation. Moreover, the peroxidative activity was enhanced by 150% after exposure to 50% (v/v) acetone for 40 h. A semi-preparative production of 4-OH-ß-ionone on a 100 mL scale resulted in a 54.2% isolated yield with 95% purity. With its high expression level, rMfiUPO is a promising candidate as an excellent parental template for enhancing desirable traits such as increased stability and selectivity through directed evolution, thereby meeting the necessary criteria for practical application.

Functional metabolomics reveals arsenic-induced inhibition of linoleic acid metabolism in mice kidney in drinking water.

Arsenic (As) is a heavy metal known for its detrimental effects on the kidneys, but the precise mechanisms underlying its toxicity remain unclear. In this study, we employed an integrated approach combining traditional toxicology methods with functional metabolomics to explore the nephrotoxicity induced by As in mice. Our findings demonstrated that after 28 days of exposure to sodium arsenite, blood urea nitrogen, serum creatinine levels were significantly increased, and pathological examination of the kidneys revealed dilation of renal tubules and glomerular injury. Additionally, uric acid, total cholesterol, and low-density lipoprotein cholesterol levels were significant increased while triglyceride level was decreased, resulting in renal insufficiency and lipid disorders. Subsequently, the kidney metabolomics analysis revealed that As exposure disrupted 24 differential metabolites, including 14 up-regulated and 10 down-regulated differential metabolites. Ten metabolic pathways including linoleic acid and glycerophospholipid metabolism were significantly enriched. Then, 80 metabolic targets and 168 predicted targets were identified using metabolite network pharmacology analysis. Of particular importance, potential toxicity targets, such as glycine amidinotransferase, mitochondrial (GATM), and nitric oxide synthase, and endothelial (NOS3), were prioritized through the "metabolite-target-pathway" network. Receiver operating characteristics curve and molecular docking analyses suggested that 1-palmitoyl-2-myristoyl-sn-glycero-3-PC, linoleic acid, and L-hydroxyarginine might be functional metabolites associated with GATM and NOS3. Moreover, targeted verification result showed that the level of linoleic acid in As group was 0.4951 µg/mL, which was significantly decreased compared with the control group. And in vivo and in vitro protein expression experiments confirmed that As exposure inhibited the expression of GATM and NOS3. In conclusion, these results suggest that As-induced renal injury may be associated with the inhibition of linoleic acid metabolism through the down-regulation of GATM and NOS3, resulting in decreased levels of linoleic acid, 1-palmitoyl-2-myristoyl-sn-glycero-3-PC, and L-hydroxyarginine metabolites.

Understanding the potential of taxi sharing: The case of Chengdu.

The emergence of taxi sharing enhances urban transport efficiency and reduces carbon emissions. Using GPS tracking data from taxis in Chengdu, China, this study first outlines conditions for identifying shareable taxi orders based on their origins and destinations. We then develop a three-phase computational model to optimize matches among all potential shareable orders, calculating the shareable mileage and the proportion of original mileage that could be shared. Our comprehensive temporal and spatial analysis reveal a significant market for taxi sharing in Chengdu, with higher potential on workdays than non-workdays and four distinct demand peaks throughout the day. The morning peak on workdays and the night peak on non-workdays are particularly pronounced. Most shareable orders originate within major city districts. We find a positive correlation between the potential of taxi sharing and average traffic speed, and negative correlations with order volume, regional economic development, and population density. Functional zones related to Enterprises, Motorcycle Services, and Transportation Services exhibit significantly higher sharing potential. Compared to traditional taxi operations, taxi sharing significantly reduces total travel mileage. This quantitative analysis offers insights into the potential demand for taxi sharing among urban residents and may help government authorities optimize taxi resources for the sustainable development of urban transport.

Design, Synthesis, and Bioevaluation of Transcriptional Enhanced Assocciated Domain (TEAD) PROTAC Degraders.

Dysregulation of the Hippo pathway has been observed in various cancers. The transcription factor TEAD, together with its coactivators YAP/TAZ, plays a crucial role in regulating the transcriptional output of the Hippo pathway. Recently, extensive research has focused on small molecule inhibitors targeting TEAD, but studies on TEAD degraders are comparatively rare. In this study, we designed and synthesized a series of TEAD PROTACs by connecting a pan-TEAD inhibitor with the CRBN ligand thalidomide. A representative compound, 27, exhibited potent antiproliferative activity against NF2-deficient NCI-H226 cells. It dose-dependently induced TEAD degradation dependent on CRBN and proteasome system and decreased key YAP target genes CYR61 and CTGF expressions in NCI-H226 cells. Further degradation selectivity studies revealed that 27 exhibited more potent activity against TEAD2 compared to those of the other three family members in Flag-TEADs transfected 293T cells. Therefore, 27 may serve as a valuable tool for advancing biological studies related to TEAD2.

Mitigation of Salt Stress in Rice by the Halotolerant Plant Growth-Promoting Bacterium Enterobacter asburiae D2.

Salinity is a major abiotic stress that seriously affects crop growth worldwide. In this work, we aimed to isolate potential halotolerant plant growth-promoting rhizobacteria (PGPR) to mitigate the adverse impacts of salt stress in rice. An isolate, D2, with multiple plant growth-promoting (PGP) characteristics was identified as Enterobacter asburiae D2. Strain D2 could produce indole-3-acetic acid and siderophore. It also exhibited phosphate solubilization and 1-aminocyclopropane-1-carboxylic deaminase activity. Genome analysis further provided insights into the molecular mechanism of its PGP abilities. Strain D2 inoculation efficiently stimulated rice growth under both normal and saline conditions. Compared with the non-inoculated plants, a significant increase in plant height (18.1-34.7%), root length (25.9-57.1%), root dry weight (57.1-150%), and shoot dry weight (17.3-50.4%) was recorded in inoculated rice seedlings. Meanwhile, rice seedlings inoculated with strain D2 showed improvement in chlorophyll and proline content, while the oxidant damage was reduced in these plants in comparison with the control group. Moreover, the K+/Na+ ratio of the inoculated rice seedlings exposed to NaCl and Na2CO3 was higher than that of the uninoculated groups. These results imply that Enterobacter asburiae D2 is a potential PGPR that can be used for alleviation of salt stress in rice.

Boosting cadmium tolerance in Phoebe zhennan: the synergistic effects of exogenous nitrogen and phosphorus treatments promoting antioxidant defense and root development.

Plants possess intricate defense mechanisms to resist cadmium (Cd) stress, including strategies like metal exclusion, chelation, osmoprotection, and the regulation of photosynthesis, with antioxidants playing a pivotal role. The application of nitrogen (N) and phosphorus (P) fertilizers are reported to bolster these defenses against Cd stress. Several studies investigated the effects of N or P on Cd stress in non-woody plants and crops. However, the relationship between N, P application, and Cd stress resistance in valuable timber trees remains largely unexplored. This study delves into the Cd tolerance mechanisms of Phoebe zhennan, a forest tree species, under various treatments: Cd exposure alone, combined Cd stress with either N or P and Cd stress with both N and P application. Our results revealed that the P application enhanced root biomass and facilitated the translocation of essential nutrients like K, Mn, and Zn. Conversely, N application, especially under Cd stress, significantly inhibited plant growth, with marked reductions in leaf and stem biomass. Additionally, while the application of P resulted in reduced antioxidant enzyme levels, the combined application of N and P markedly amplified the activities of peroxidase by 266.36%, superoxide dismutase by 168.44%, and ascorbate peroxidase by 26.58% under Cd stress. This indicates an amplified capacity of the plant to neutralize reactive oxygen species. The combined treatment also led to effective regulation of nutrient and Cd distribution in roots, shoots, and leaves, illustrating a synergistic effect in mitigating toxic impact of N. The study also highlights a significant alteration in photosynthetic activities under different treatments. The N addition generally reduced chlorophyll content by over 50%, while P and NP treatments enhanced transpiration rates by up to 58.02%. Our findings suggest P and NP fertilization can manage Cd toxicity by facilitating antioxidant production, osmoprotectant, and root development, thus enhancing Cd tolerance processes, and providing novel strategies for managing Cd contamination in the environment.

A novel approach combining network pharmacology and experimental validation to study the protective effect of ginsenoside Rb1 against cantharidin-induced hepatotoxicity in mice.

Cantharidin (CTD) is a widely used anticancer compound, but its clinical use is mainly limited due to hepatotoxicity. Ginsenoside Rb1 (GRb1) shows potential hepatoprotective effects. Nonetheless, the protective effect and underlying mechanism of GRb1 against CTD-induced hepatotoxicity in mice have not been investigated. This study aims to elucidate the effect and mechanism of GRb1 on CTD-induced hepatotoxicity using network pharmacology and in vivo experiments. Network pharmacology studies have shown that 263 targets were the main mechanisms by which GRb1 alleviates CTD-induced hepatotoxicity. KEGG enrichment analysis revealed that 75 hub genes were mainly enriched in TNF, IL-17 and apoptosis signalling pathways. Molecular docking analysis showed that GRb1 exhibited high affinity with Akt1, Tnf, Il6, Bcl2 and Caspase3. In addition, results from animal studies demonstrated that GRb1 could ameliorate CTD-induced hepatotoxicity by inhibiting protein expression of Caspase-3, Caspase-8, Bcl-2/Bax, GRP78, ATF6, ATF4, CHOP, IRE1α and PERK. This research revealed the mechanism of GRb1 against CTD-induced hepatotoxicity by inhibiting apoptosis and endoplasmic reticulum stress (ERS) and it may provide a scientific rationale for the potential use of GRb1 in the treatment of hepatotoxicity induced by CTD.

NAMPT­NAD+ is involved in the senescence­delaying effects of saffron in aging mice.

As the proportion of the elderly population grows rapidly, the senescence-delaying effects of Traditional Chinese Medicine is being investigated. The aim of the present study was to investigate the senescence-delaying effects of saffron in naturally aging mice. The active ingredients in an aqueous saffron extract were determined using high-performance liquid chromatography (HPLC). Mice were divided into saffron (8- and 16-months-old) and control groups (3-, 8-, and 16-months-old), and saffron extract was administered to the former groups for 8 weeks. The open field test and Barnes maze test were used to evaluate the locomotor activity, learning and memory function of the mice. The levels of inflammatory factors in the brain were determined by ELISA. In addition, the activities of acetylcholinesterase (AChE) and superoxide dismutase, and the contents of malondialdehyde and nicotinamide adenine dinucleotide (NAD+) were detected by enzyme immunoassay, and the content of NAMPT was detected by ELISA, western blotting and reverse transcription-quantitative PCR. The cellular distribution of NAMPT and synaptic density were evaluated by immunofluorescence, and the pathological morphologies of the liver, skin, kidneys were observed by hematoxylin and eosin staining. HPLC revealed that the crocin and picrocrocin contents of the saffron extract were 19.56±0.14 and 12.00±0.13%, respectively. Saffron exhibited the potential to improve the learning and memory function in aging mice as it increased synaptic density and decreased AChE activity. Also, saffron ameliorated the pathological changes associated with organ aging, manifested by increasing the number of hepatocytes and the thickness of the skin, and preventing the aging-induced ballooning and bleeding in the kidneys. Furthermore, saffron increased the contents of NAMPT and NAD+ in the brain and decreased the content of NAMPT in the serum. In addition, it changed the cellular distribution of NAMPT in aging mice, manifested as reduced NAMPT expression in microglia and astrocytes, and increased NAMPT expression in neurons. Saffron also decreased the contents of proinflammatory cytokines and oxidative stress factors in aging mice. Altogether, these findings indicate that saffron exerts senescence-delaying effects in naturally aging mice, which may be associated with the NAMPT-NAD+ pathway.

A novel M2-like tumor associated macrophages-related gene signature for predicting the prognosis and immunotherapy efficacy in gastric cancer.

BACKGROUND: M2-like tumor-associated macrophages (M2-like TAMs) play key roles in tumor progression and the immune response. However, the clinical significance and prognostic value of M2-like TAMs-associated regulatory genes in gastric cancer (GC) have not been clarified. METHODS: Herein, we identified M2-like TAM-related genes by weighted gene coexpression network analysis of TCGA-STAD and GSE84437 cohort. Lasso-Cox regression analyses were then performed to screen for signature genes, and a novel signature was constructed to quantify the risk score for each patient. Tumor mutation burden (TMB), survival outcomes, immune cells, and immune function were analyzed in the risk groups to further reveal the immune status of GC patients. A gene-drug correlation analysis and sensitivity analysis of anticancer drugs were used to identify potential therapeutic agents. Finally, we verified the mRNA expression of signature genes in patient tissues by qRT-PCR, and analyzed the expression distribution of these genes by IHC. RESULTS: A 4-gene (SERPINE1, MATN3, CD36, and CNTN1) signature was developed and validated, and the risk score was shown to be an independent prognostic factor for GC patients. Further analyses revealed that GC patients in the high-risk group had a worse prognosis than those in the low-risk group, with significant differences in TMB, clinical features, enriched pathways, TIDE score, and tumor microenvironment features. Finally, we used qRT-PCR and IHC analysis to verify mRNA and protein level expression of signature genes. CONCLUSION: These findings highlight the importance of M2-like TAMs, provide a new perspective on individualized immunotherapy for GC patients.

A New Approach for Exploring Reperfusion Brain Damage in Hypoxic Ischemic Encephalopathy.

Reperfusion is an essential pathological stage in hypoxic ischemic encephalopathy (HIE). Although the Rice-Vannucci model is widely used in HIE research, it remains difficult to replicate HIE-related reperfusion brain injury. The purpose of this study is to establish a rat model of hypoxia ischemia reperfusion brain damage (HIRBD) using a common carotid artery (CCA) muscle bridge in order to investigate the mechanisms of cerebral resistance to hypoxic-ischemic and reperfusion brain damage. Random assignment of Sprague-Dawley (SD) rats to the Sham, HIRBD, and Rice-Vannucci groups. Changes in body weight, mortality rate, spontaneous alternation behavior test (SAB test), and dynamic changes in cerebral blood flow (CBF) were detected. The damaged cerebral cortices were extracted for morphological comparison, transcriptomic analysis, and quantitative real-time PCR. Harvesting the hippocampus for transmission electron microscopy (TEM) detection. As a result, CCA muscle bridge could effectively block CBF, which recovered after the muscle bridge detachment. Pathological comparison, the SAB test, and TEM analysis revealed that brain damage in Rice-Vannucci was more severe than HIRBD. Gpx1, S100a6, Cldn5, Esr1, and Gfap were highly expressed in both HIRBD and Rice-Vannucci. In conclusion, the CCA muscle bridge-established HIRBD model could be used as an innovative and dependable model to simulate pathological process of HIRBD.

Identification of biomarkers associated with pediatric asthma using machine learning algorithms: A review.

Pediatric asthma is a complex disease with a multifactorial etiology. The identification of biomarkers associated with pediatric asthma can provide insights into the pathogenesis of the disease and aid in the development of novel diagnostic and therapeutic strategies. This study aimed to identify potential biomarkers for pediatric asthma using Weighted Gene Co-expression Network Analysis (WGCNA) and machine learning algorithms. We obtained gene expression data from publicly available databases and performed WGCNA to identify gene co-expression modules associated with pediatric asthma. We then used machine learning algorithms, including random forest, lasso regression algorithm, and support vector machine-recursive feature elimination, to classify asthma cases and controls based on the identified gene modules. We also performed functional enrichment analyses to investigate the biological functions of the identified genes.We detected 24,544 genes exhibiting differential expression between controlled and uncontrolled genes from the GSE135192 dataset. In the combined WCGNA analysis, a total of 104 co-expression genes were screened, both controlled and uncontrolled. After screening, 11 hub genes were identified. They were AK2, PDK4, PER3, GZMH, NUMBL, NRL, SCO2, CREBZF, LARP1B, RXFP1, and VDAC3P1. The areas under their receiver operating characteristic curve were above 0.78. Our study identified potential biomarkers for pediatric asthma using WGCNA and machine learning algorithms. Our findings suggest that 11 hub genes could be used as novel diagnostic markers and treatment targets for pediatric asthma. These findings provide new insights into the pathogenesis of pediatric asthma and may aid in the development of novel diagnostic and therapeutic strategies.

Treatment of Tourette syndrome by acupuncture combined with Chinese medicine based on syndrome differentiation: A review.

Tourette syndrome (TS) is a chronic neurodevelopmental disorder characterized by involuntary motor and speech tics, which can greatly reduce the quality of life of patients. The pathophysiology of TS involves both genetic and environmental factors. Assessing TS pathogenesis is complex, and its underlying pathophysiology is not fully understood. It is gratifying that the research in the past 5 years has brought new research progress on the genetic, neurophysiological and brain network changes of TS. However, despite the progress of research, the treatment methods and drugs of modern medicine are still unsatisfactory, and it is difficult to achieve satisfactory results. Traditional Chinese medicine, as a part of complementary and alternative medicine, has unique efficacy in the treatment of TS, and the safety of its treatment is also worthy of attention. Based on the latest achievements in the pathophysiology of TS, this article will discuss the treatment of TS by acupuncture combined with medicine.