Effects of regulating gut microbiota by electroacupuncture in the chronic unpredictable mild stress rat model.

OBJECTIVE: This study aims to investigate the effect of electroacupuncture (EA) treatment on depression, and the potential molecular mechanism of EA in depression-like behaviors rats. METHODS: A total of 40 male Sprague Dawley rats were divided into three groups: normal control, chronic unpredictable mild stress (CUMS), and EA (CUMS + EA). The rats in CUMS and EA groups underwent chronic stress for 10 weeks, and EA group rats received EA treatment for 4 weeks starting from week 7. Body weight and behavioral tests, including the sucrose preference test (SPT), the forced swimming test (FST), and the open field test (OFT) were monitored. Gut microbiota composition was assessed via 16S rDNA sequencing, and lipid metabolism was analyzed by using UPLC-Q-TOF/MS technology. RESULTS: In comparison to CUMS group, EA could improve the behavior including bodyweight, immovability time, sucrose preference index, crossing piece index and rearing times index. After 4 weeks of EA treatment, 5-HT in hippocampus, serum and colon of depressive rats were simultaneously increased, indicating a potential alleviation of depression-like behaviors. In future studies revealed that EA could regulate the distribution and functions of gut microbiota, and improve the intestinal barrier function of CUMS rats. The regulation of intestinal microbial homeostasis by EA may further affect lipid metabolism in CUMS rats, and thus play an antidepressant role. CONCLUSION: This study suggested that EA has potential antidepressant effects by regulating gut microbiota composition and abundance, subsequently affecting lipid metabolism.

Induction of hepatic fibrosis in mice with schistosomiasis by extracellular microRNA-30 derived from Schistosoma japonicum eggs.

Background: Schistosomiasis is a zoonotic parasitic disorder induced by the infestation of schistosomes, a genus of trematodes. MicroRNAs (miRNAs) in egg-derived exosomes are crucial for modulating the host's immune responses and orchestrating the pathophysiological mechanisms. Although the exosomes secreted by S. japonicum contain abundant miRNAs, the specific roles of these miRNAs in the pathogenesis of schistosomiasis-induced hepatic fibrosis are yet to be comprehensively elucidated. The egg exosomes of S. japonicum secrete miRNA-30, a novel miRNA. Methods: In vitro, the effect of miRNA-30 was evaluated by transfecting HSCs with miRNA mimics. The target gene biosignature for miRNA-30 was predicted using the miRDB software. The effect of miRNA-30 in hepatic fibrosis was evaluated by either elevating its expression in healthy mice or by inhibiting its activity in infected mice by administration of recombinant adeno-associated virus serotype eight vectors expressing miRNA-30 or miRNA sponges. Results: This novel miRNA can activate hepatic stellate cells (HSCs), the prinary effector cells of hepatic fibrosis, in vitro, i.e., it significantly increases the fibrogenic factors Col1(α1), Col3(α1), and α-SMA at both mRNA and protein levels. In addition, miRNA-30 may activate HSCs by targeting the host RORA gene. In addition, in vivo experiments were conducted by administering a recombinant adeno-associated viral vector to modulate the expression levels of miRNA-30. The overexpression of miRNA-30 in healthy mice significantly elevated the expression of Col1(α1), Col3(α1), and α-SMA at both the transcriptomic and proteomic scales. This overexpression was coupled with a pronounced augmentation in the hepatic hydroxyproline content. Conversely, the in vivo silencing of miRNA-30 in infected mice induced a considerable reduction in the size of hepatic granulomas and areas of collagen deposition. Hence, in vivo, modulation of miRNA-30 expression may play a pivotal role in ameliorating the severity of hepatic fibrosis in mice afflicted with S. japonica. Conclusions: The study results suggest that miRNA-30 may augment schistosomiasis-induced hepatic fibrosis through a probable interaction with the host RORA. Our study may improve the current theoretical framework regarding cross-species regulation by miRNAs of hepatic fibrosis in schistosomiasis.

Early-onset palatal myoclonus in Wernekinck commissure syndrome secondary to caudal paramedian midbrain infarction: A case report and a mini review of the literature.

INTRODUCTION: Wernekinck commissure syndrome (WCS) is an extremely rare midbrain syndrome, which selectively destroys the decussation of the superior cerebellar peduncle and the central tegmental tract, which commonly presents with bilateral cerebellar ataxia, dysarthria, and internuclear ophthalmoplegia. Palatal myoclonus in Wernekinck commissure syndrome is uncommon and often occurs as a late phenomenon due to hypertrophic degeneration of bilateral inferior olivary nuclei. MATERIAL AND METHOD: A patient with WCS, admitted to our hospital from December 2023, was chosen for this study, and the syndrome's clinical manifestations, imaging features, and etiology were retrospectively analyzed based on the literature. A 68-year-old right-handed East Asian man presented with dizziness, slurred speech, difficulty with swallowing and walking, and rhythmic contractions of the soft palate. He had several risk factors for ischemic cerebrovascular diseases (age, sex, dyslipidemia, hypertension and smoking history). Brain magnetic resonance imaging showed hyperintensity of DWI and hypointensity of ADC at the caudal midbrain which was around the paramedian mesencephalic tegmentum anterior to the aqueduct of midbrain. RESULTS: He was diagnosed with Wernekinck commissure syndrome (WCS) secondary to caudal paramedian midbrain infarction. He was started on dual antiplatelet therapy (aspirin and clopidogrel) and intensive statin therapy. Blood pressure and glucose were also adjusted. His symptoms improved rapidly, and he walked steadily and speak clearly after 7 days of treatment. CONCLUSIONS: Palatal myoclonus is known to occur as a late phenomenon due to hypertrophic degeneration of bilateral inferior olivary nuclei. However, Our case suggests that palatal myoclonus can occur in the early stages in WCS.

Novel antibody-drug conjugates based on DXd-ADC technology.

In recent years, antibody-drug conjugate (ADC) technology, which uses monoclonal antibodies (mAbs) to specifically deliver effective cytotoxic payloads to tumor cells, has become a promising method of tumor targeted therapy. ADCs are a powerful class of biopharmaceuticals that link antibodies targeting specific antigens and small molecule drugs with potent cytotoxicity via a linker, thus enabling selective destruction of cancer cells while minimizing systemic toxicity. DXd is a topoisomerase I inhibitor that induces DNA damage leading to cell cycle arrest, making it an option for ADC payloads. The DXd-ADC technology, developed by Daiichi Sankyo, is a cutting-edge platform that produces a new generation of ADCs with improved therapeutic metrics and has shown significant therapeutic potential in various types of cancer. This review provides a comprehensive assessment of drugs developed with DXd-ADC technology, with a focus on mechanisms of action, pharmacokinetics studies, preclinical data, and clinical outcomes for DS-8201a, U3-1402, DS-1062a, DS-7300a, DS-6157a, and DS-6000a. By integrating existing data, we aim to provide valuable insights into the current therapeutic status and future prospects of these novel agents.

Colored Radiative Cooling and Flame-Retardant Polyurethane-Based Coatings: Selective Absorption/Reflection in Solar Waveband.

The aesthetic demand has become an imperative challenge to advance the practical and commercial application of daytime radiative cooling technology toward mitigating climate change. Meanwhile, the application of radiative cooling materials usually focuses on the building surface, related tightly to fire safety. Herein, the absorption and reflection spectra of organic and inorganic colorants are first compared in solar waveband, finding that iron oxides have higher reflectivity in NIR region. Second, three kinds of iron oxides-based colorants are selected to combine porous structure and silicon-modified ammonium polyphosphate (Si-APP) to engineer colored polyurethane-based (PU) coating, thus enhancing the reflectivity and flame retardancy. Together with reflectivity of more than 90% in near-infrared waveband and infrared emissivity of ≈91%, average temperature drops of ≈5.7, ≈7.9, and ≈3.8 °C are achieved in porous PU/Fe2O3/Si-APP, porous PU/Fe2O3·H2O/Si-APP, and porous PU/Fe3O4·H2O/Si-APP, compared with dense control samples. The catalysis effect of iron oxides in the cross-linking reaction of pyrolysis products and dehydration mechanism of Si-APP enable PU coating to produce an intumescent and protective char residue. Consequently, PU composite coatings demonstrate desirable fire safety. The ingenious choice of colorants effectively minimizes the solar heating effect and trades off the daytime radiative cooling and aesthetic appearance requirement.

Does androgenic alopecia aggravate the risk of prostate cancer? Evidence from Mendelian randomization.

Background: Epidemiological reports indicate a potential association between androgenic alopecia (AGA) and increased prostate cancer (PC) prevalence, but conflicting reports also exist. This study aims to elucidate the causality of AGA on PC risk using Mendelian randomization (MR) analysis. Materials and methods: Two-sample MR analyses utilized public genome-wide association studies summary data for single-nucleotide polymorphisms associated with AGA. Four statistical methods were used: inverse variance weighted (IVW), MR-Egger, weighted median, and weighted mode, with IVW as the preliminary estimation method. Additionally, sensitivity analyses were conducted to address pleiotropic bias. Results: Genetically proxied AGA did not demonstrate a causal effect on PC risk (IVW P > 0.05). Consistently, complementary methods yielded results aligned with IVW. Conclusions: Our MR analysis indicates no causal relationship between genetically predicted AGA and PC risk, suggesting that observed associations in epidemiological studies may not be causal.

Causal Relationship Between Obstructive Sleep Apnea and Temporomandibular Disorders: A Bidirectional Mendelian Randomization Analysis.

Objective: This study was conducted to investigate the bidirectional causal relationship between obstructive sleep apnea (OSA) and temporomandibular disorders (TMD). Methods: Using an online pooled dataset of genome-wide association studies (GWAS), a two-sample bi-directional Mendelian randomization (MR) method was implemented. Inverse variance weighting was used as the primary analyses approach, and other methods of MR Egger, weighted median method, MR-Egger, Simple mode, and Weighted mode analysis were conducted as supplements to evaluate the causal relationship between OSA and TMD with odds ratios (OR) and 95% confidence interval (CI). Furthermore, the Cochran Q, MR-Egger, and MR-PRESSO approaches were used to perform the heterogeneity test and multiple validity. Results: The general results of the forward MR analysis indicated that OSA had a significant causal influence on TMD (OR=1.241, 95% CI: 1.009-1.526, P=0.041), but no significant correlation was observed in the reverse MR analysis (IVW: OR=0.975, 95% CI=0.918-1.036, P=0.411). Conclusion: In summary, our research demonstrated a hereditary causative relationship between OSA and TMD, indicating that appropriate intervention is required for both prevention and treatment of TMD.

Engineering robust and transparent dual-crosslinked hydrogels for multimodal sensing without conductive additives.

Conductive hydrogels are pivotal for the advancement of flexible sensors, electronic skin, and healthcare monitoring systems, facilitating transformative innovations. However, issues such as inadequate intrinsic compatibility, mismatched mechanical properties, and limited stability curtail their potential, resulting in compromised device efficacy and performance degradation. In this research, we engineered functional hydrogels featuring a dual-crosslinked network composed of (PA/PVA)-P(AM-AA) to address these challenges. This design eliminates the need for conductive additives, thereby enhancing intrinsic compatibility. Notably, the hydrogels exhibit exceptional mechanical properties, with high tensile strength (∼700 %), Young's modulus (∼5.33 MPa), increased strength (∼2.46 MPa) and toughness (∼6.59 MJ m-3). They also achieve a compressive strength of âˆ¼7.33 MPa at 80 % maximal compressive strain and maintain about 89 % transparency. Moreover, flexible sensors derived from these hydrogels demonstrate enhanced multimodal sensing capabilities, including temperature, strain, and pressure detection, enabling precise monitoring of human movements. The integration of multiple hydrogels into a three-dimensional sensor array facilitates detailed spatial pressure distribution mapping. By strategically applying dual-crosslinked network engineering and eliminating conductive additives, we have streamlined the design and manufacturing of hydrogels to meet the rising demand for high-performance wearable sensors.

Ammonia recovery via direct contact membrane distillation: Modeling and performance optimization.

Ammonia recovery from wastewater has positive environmental benefits, avoiding eutrophication and reducing production energy consumption, which is one of the most effective ways to manage nutrients in wastewater. Specifically, ammonia recovery by membrane distillation has been gradually adopted due to its excellent separation properties for volatile substances. However, the global optimization of direct contact membrane distillation (DCMD) operating parameters to maximize ammonia recovery efficiency (ARE) has not been attempted. In this work, three key operating factors affecting ammonia recovery, i.e., feed ammonia concentration, feed pH, and DCMD running time, were identified from eight factors, by a two-level Plackett-Burman Design (PBD). Subsequently, Box-Behnken design (BBD) under the response surface methodology (RSM) was used to model and optimize the significant operating parameters affecting the recovery of ammonia though DCMD identified by PBD and statistically verified by analysis of variance (ANOVA). Results showed that the model had a high coefficient of determination value (R2 = 0.99), and the interaction between NH4Cl concentration and feed pH had a significant effect on ARE. The optimal operating parameters of DCMD as follows: NH4Cl concentration of 0.46 g/L, feed pH of 10.6, DCMD running time of 11.3 h, and the maximum value of ARE was 98.46%. Under the optimized conditions, ARE reached up to 98.72%, which matched the predicted value and verified the validity and reliability of the model for the optimization of ammonia recovery by DCMD process.

Metagenomic Next-Generation Sequencing as an Effective Diagnostic Tool for Talaromycosis in HIV-Negative Patients.

The diagnosis of Talaromyces marneffei infection in HIV-negative patients remains challenging. There is an urgent need for rapid and convenient methods to diagnose this complicated disease. The aim of this study was to evaluate the diagnostic efficiency of metagenomic next-generation sequencing (mNGS) for talaromycosis in non-HIV-infected patients by comparing mNGS with traditional microbial culture. In total, 66 samples from 57 patients were analyzed via both mNGS and microbial culture. The ROC curve showed a sensitivity for mNGS of 97.22%, which was greater than that of microbial culture (61.11%). Samples from the respiratory tract, infectious skin lesions, and lymph nodes are recommended as routine samples for talaromycosis detection via mNGS. Furthermore, mNGS significantly reduced the diagnostic time compared to microbial culture. Overall, our study demonstrated that mNGS is a promising tool for rapid and accurate pathogenic detection in HIV-negative patients with talaromycosis.

Final analysis of a phase II trial of neoadjuvant chemoimmunotherapy for locoregionally advanced head and neck squamous cell carcinoma.

OBJECTIVES: Neoadjuvant chemoimmunotherapy has shown promising results for resectable, locoregionally advanced (LA) head and neck squamous cell carcinoma (L/A HNSCC). We published the first phase II trial of neoadjuvant camrelizumab combined with chemotherapy in resectable, L/A HNSCC, demonstrating it was safe and feasible with favorable pathological complete response (pCR). Here, we report the final analysis results for neoadjuvant chemoimmunotherapy in L/A HNSCC (minimum 2.0 years of follow-up). MATERIALS AND METHODS: Three cycles of chemoimmunotherapy were administered before surgery to patients with L/A HNSCC. Two-year disease-free survival (DFS), overall survival (OS) and quality of life (QOL) were reported. RESULTS: The overall two-year DFS and OS rates were 90 % and 100 %, respectively. With a median follow-up of 33.7 months, 9 of 10 (90 %) patients with pCR were alive and disease free. Patients with TNM stage (II/III) or < 20 % of residual viable tumor trended toward improved DFS; hazard ratio (HR), 0.44 [95 % confidence interval (CI), 0.04-5.28] and HR, 0.26 (95 % CI, 0.03-2.36), respectively. All QLQ-C30 functioning and symptom scales other than nausea and vomiting were resolved at 2 years after the completion of radiotherapy. CONCLUSION: Neoadjuvant camrelizumab in combination with chemotherapy provided encouraging clinical outcomes for patients with L/A HNSCC. Further studies with longer follow-up and larger samples are warranted. TRIAL REGISTRATION: Chictr.org.cn, ChiCTR1900025303. Registered Aug 22, 2019. https://www.chictr.org.cn/showproj.html?proj=41380.

The microbiome compositional and functional differences between rectal mucosa and feces.

In recent years, most studies on the gut microbiome have primarily focused on feces samples, leaving the microbial communities in the intestinal mucosa relatively unexplored. To address this gap, our study employed shotgun metagenomics to analyze the microbial compositions in normal rectal mucosa and matched feces from 20 patients with colonic polyps. Our findings revealed a pronounced distinction of the microbial communities between these two sample sets. Compared with feces, the mucosal microbiome contains fewer genera, with Burkholderia being the most discriminating genus between feces and mucosa, highlighting its significant influence on the mucosa. Furthermore, based on the microbial classification and KEGG Orthology (KO) annotation results, we explored the association between rectal mucosal microbiota and factors such as age, gender, BMI, and polyp risk level. Notably, we identified novel biomarkers for these phenotypes, such as Clostridium ramosum and Enterobacter cloacae in age. The mucosal microbiota showed an enrichment of KO pathways related to sugar transport and short chain fatty acid metabolism. Our comprehensive approach not only bridges the knowledge gap regarding the microbial community in the rectal mucosa but also underscores the complexity and specificity of microbial interactions within the human gut, particularly in the Chinese population. IMPORTANCE: This study presents a system-level map of the differences between feces and rectal mucosal microbial communities in samples with colorectal cancer risk. It reveals the unique microecological characteristics of rectal mucosa and its potential influence on health. Additionally, it provides novel insights into the role of the gut microbiome in the pathogenesis of colorectal cancer and paves the way for the development of new prevention and treatment strategies.

Kaolin-Derived Porous Silico-Aluminate Nanoparticles as Absorbents for Emergency Disposal of Toluene Leakage.

To rapidly eliminate toluene from aqueous environments during leakage accidents, this paper synthesized porous silico-aluminate nanoparticles (SANs) via a hydrothermal method, using cost-effective and non-toxic natural kaolin as the basic raw material. The morphology and structure of the porous SANs were characterized using scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and BET-specific surface area tests. The effects of different conditions, such as the dosage of porous SANs, initial concentration of toluene, temperature, capture time, and pH, on the adsorption performance of porous SANs were analyzed. The as-prepared SANs exhibited a high removal efficiency and rapid adsorption performance toward toluene in aqueous solution. Finally, the kinetics of the adsorption of toluene in aqueous solution by porous SANs were investigated. The mechanism of the adsorption of toluene by porous SANs was further discussed. These findings provide a cost-effective and highly efficient absorbent for the emergency disposal of toluene leakage accidents.

Improving Sag Resistance in Geopolymer Coatings Using Diatomite Filler: Effects on Rheological Properties and Early Hydration.

The reduction in the rheological parameters and dissolution rate of precursors in geopolymer coatings during early hydration significantly contributes to sagging. This study aims to improve the sag resistance of these coatings by incorporating diatomite filler. Rheological testing was conducted to assess the impact of diatomite and its concentration on the yield stress, plastic viscosity, and thixotropy of the geopolymer coatings. The results indicated that diatomite's large specific surface area and high reactivity have a significant influence on the rheological parameters and early dissolution rate of precursors. With a diatomite concentration of 1.1%, the coating exhibited a yield stress of 2.749 Pa and a plastic viscosity of 0.921 Pa·s, maintaining stability, homogeneity, and no sagging at a thickness of 600 µm. Furthermore, the highly active SiO2 in diatomite participates in the secondary hydration reaction of the geopolymer materials led to the formation of substantial C-(A)-S-H gel. This gel enhances internal interconnectivity within the coating, thereby improving its rheological and mechanical properties.

Microcapsule Modification Strategy Empowering Separator Multifunctionality to Enhance Safety of Lithium-Metal Batteries.

The uncontrollable growth of lithium dendrites and the flammability of electrolytes are the direct impediments to the commercial application of high-energy-density lithium metal batteries (LMBs). Herein, this study presents a novel approach that combines microencapsulation and electrospinning technologies to develop a multifunctional composite separator (P@AS) for improving the electrochemical performance and safety performance of LMBs. The P@AS separator forms a dense charcoal layer through the condensed-phase flame retardant mechanism causing the internal separator to suffocate from lack of oxygen. Furthermore, it incorporates a triple strategy promoting the uniform flow of lithium ions, facilitating the formation of a highly ion-conducting solid electrolyte interface (SEI), and encouraging flattened lithium deposition with active SiO2 seed points, considerably suppressing lithium dendrites growth. The high Coulombic efficiency of 95.27% is achieved in Li-Cu cells with additive-free carbonate electrolyte. Additionally, stable cycling performance is also maintained with a capacity retention rate of 93.56% after 300 cycles in LFP//Li cells. Importantly, utilizing P@AS separator delays the ignition of pouch batteries under continuous external heating by 138 s, causing a remarkable reduction in peak heat release rate and total heat release by 23.85% and 27.61%, respectively, substantially improving the fire safety of LMBs.

Detection of HBV DNA integration in plasma cell-free DNA of different HBV diseases utilizing DNA capture strategy.

The landscape of hepatitis B virus (HBV) integration in the plasma cell-free DNA (cfDNA) of HBV-infected patients with different stages of liver diseases [chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC)] remains unclear. In this study, we developed an improved strategy for detecting HBV DNA integration in plasma cfDNA, based on DNA probe capture and next-generation sequencing. Using this optimized strategy, we successfully detected HBV integration events in chimeric artificial DNA samples and HBV-infected HepG2-NTCP cells at day one post infection, with high sensitivity and accuracy. The characteristics of HBV integration events in the HBV-infected HepG2-NTCP cells and plasma cfDNA from HBV-infected individuals (CHB, LC, and HCC) were further investigated. A total of 112 and 333 integration breakpoints were detected in the HepG2-NTCP cells and 22 out of 25 (88%) clinical HBV-infected samples, respectively. In vivo analysis showed that the normalized number of support unique sequences (nnsus) in HCC was significantly higher than in CHB or LC patients (P values â€‹< â€‹0.05). All integration breakpoints are randomly distributed on human chromosomes and are enriched in the HBV genome around nt 1800. The majority of integration breakpoints (61.86%) are located in the gene-coding region. Both non-homologous end-joining (NHEJ) and microhomology-mediated end-joining (MMEJ) interactions occurred during HBV integration across the three different stages of liver diseases. Our study provides evidence that HBV DNA integration can be detected in the plasma cfDNA of HBV-infected patients, including those with CHB, LC, or HCC, using this optimized strategy.

The biomedical knowledge graph of symptom phenotype in coronary artery plaque: machine learning-based analysis of real-world clinical data.

A knowledge graph can effectively showcase the essential characteristics of data and is increasingly emerging as a significant means of integrating information in the field of artificial intelligence. Coronary artery plaque represents a significant etiology of cardiovascular events, posing a diagnostic challenge for clinicians who are confronted with a multitude of nonspecific symptoms. To visualize the hierarchical relationship network graph of the molecular mechanisms underlying plaque properties and symptom phenotypes, patient symptomatology was extracted from electronic health record data from real-world clinical settings. Phenotypic networks were constructed utilizing clinical data and protein‒protein interaction networks. Machine learning techniques, including convolutional neural networks, Dijkstra's algorithm, and gene ontology semantic similarity, were employed to quantify clinical and biological features within the network. The resulting features were then utilized to train a K-nearest neighbor model, yielding 23 symptoms, 41 association rules, and 61 hub genes across the three types of plaques studied, achieving an area under the curve of 92.5%. Weighted correlation network analysis and pathway enrichment were subsequently utilized to identify lipid status-related genes and inflammation-associated pathways that could help explain the differences in plaque properties. To confirm the validity of the network graph model, we conducted coexpression analysis of the hub genes to evaluate their potential diagnostic value. Additionally, we investigated immune cell infiltration, examined the correlations between hub genes and immune cells, and validated the reliability of the identified biological pathways. By integrating clinical data and molecular network information, this biomedical knowledge graph model effectively elucidated the potential molecular mechanisms that collude symptoms, diseases, and molecules.