Supported Au single atoms and nanoparticles on MoS2 for highly selective CO2-to-CH3COOH photoreduction.

Effectively controlling the selective conversion of CO2 photoreduction to C2 products presents a significant challenge. Here, we develop a heterojunction photocatalyst by controllably implanting Au nanoparticles and single atoms into unsaturated Mo atoms of edge-rich MoS2, denoted as Aun/Au1-CMS. Photoreduction of CO2 results in the production of CH3COOH with a selectivity of 86.4%, which represents a 6.4-fold increase compared to samples lacking single atoms, and the overall selectivity for C2 products is 95.1%. Furthermore, the yield of CH3COOH is 22.4 times higher compared to samples containing single atoms and without nanoparticles. Optical experiments demonstrate that the single atoms domains can effectively capture photoexcited electrons by the Au nanoparticles, or the local electric field generated by the nanoparticles promotes the transfer of photogenerated electrons in MoS2 to Au single atoms, prolonging the relaxation time of photogenerated electrons. Mechanistic investigations reveal that the orbital coupling of Au5d and Mo4d strengthens the oxygen affinity of Mo and carbon affinity of Au. The hybridized orbitals reduce energy splitting levels of CO molecular orbitals, aiding C-C coupling. Moreover, the Mo-Au dual-site stabilize the crucial oxygen-associated intermediate *CH2CO, thereby enhancing the selectivity towards CH3COOH. The cross-scale heterojunctions provide an effective strategy to simultaneously address the kinetical and thermodynamical limitations of CO2-to-CH3COOH conversion.

Joint effects of tobacco smoke exposure and heavy metals on serum sex hormones in adult males.

OBJECTIVE: This study aimed to explore the associations of tobacco smoke exposure (TSE) and heavy metal exposure on sex hormones and the joint effects between them in adult males. METHODS: The study used data of 2244 adult males from the National Health and Nutrition Examination Survey (NHANES, 2013-2016). Weighted linear regression models were used to calculate their beta (ß) coefficients and corresponding confidence interval (95% CI), which assessed the joint effects of TSE and heavy metals on sex hormones. RESULTS: Sex hormone-binding globulin (SHBG) showed a positive association with increased per standard deviation (SD) for cotinine (ß=0.024 [0.004, 0.043]; P<0.001), lead (ß=0.021 [0.002, 0.039]; P=0.028), and cadmium (ß=0.034 [0.015, 0.053]; P<0.001). Manganese was positively associated with estradiol (E2) (ß=0.025 [0.009, 0.042]; P=0.002). The subjects with higher cadmium levels were more likely to have higher total testosterone (TT) (ß=0.042 [0.023, 0.062]; P<0.001). TSE and lead exerted synergistic effects on TT (p for interaction = 0.015) and E2 (p for interaction = 0.009), as also did TSE and cadmium on SHBG (p for interaction = 0.037). Compared with the reference group, TSE participants who were exposed to high concentrations of lead, cadmium, mercury, and manganese had significantly elevated TT levels, but these high levels presented no significant association with E2 levels. A significantly higher level of SHBG among TSE participants was detected in high concentrations for lead, cadmium, and mercury. CONCLUSION: TSE exacerbated sex hormone imbalances when combined with high levels of metal exposure. Smoking cessation is crucial, especially in the case of high levels of occupational exposure to heavy metals.

Identification of significant biomarkers for predicting the risk of bipolar disorder with arteriosclerosis based on integrative bioinformatics and machine learning.

Introduction: Increasing evidence has indicated a connection between bipolar disorder (BD) and arteriosclerosis (AS), yet the specific molecular mechanisms remain unclear. This study aims to investigate the hub genes and molecular pathways for BD with AS. Methods: BD-related dataset GSE12649 were downloaded from the Gene Expression Omnibus database and differentially expressed genes (DEGs) and key module genes derived from Limma and weighted gene co-expression network analyses (WGCNA) were identified. AS-related genes were sourced from the DisGeNET database, and the overlapping genes between DEGs and AS-related genes were characterized as differentially expressed arteriosclerosis-related genes (DE-ASRGs). The functional enrichment analysis, protein-protein interaction (PPI) network and three machine learning algorithms were performed to explore the hub genes, which were validated with two external validation sets. Additionally, immune infiltration was performed in BD. Results: Overall, 67 DE-ASRGs were found to be overlapping between the DEGs and AS-related genes. Functional enrichment analysis highlighted the cancer pathways between BD and AS. We identified seven candidate hub genes (CTSD, IRF3, NPEPPS, ST6GAL1, HIF1A, SOX9 and CX3CR1). Eventually, two hub genes (CX3CR1 and ST6GAL1) were identified as BD and AS co-biomarkers by using machine learning algorithms. Immune infiltration had revealed the disorder of immunocytes. Discussion: This study identified the hub genes CX3CR1 and ST6GAL1 in BD and AS, providing new insights for further research on the bioinformatic mechanisms of BD with AS and contributing to the diagnosis and prevention of AS in psychiatric clinical practice.

Carcinomembrane-Camouflaged Perfluorochemical Dual-Layer Nanopolymersomes Bearing Indocyanine Green and Camptothecin Effectuate Targeting Photochemotherapy of Cancer.

Photochemotherapy has been recognized as a promising combinational modality for cancer treatment. However, difficulties such as off-target drug delivery, systemic toxicity, and the hypoxic nature of the tumor microenvironment remain hindrances to its application. To overcome these challenges, cancer cell membrane camouflaged perfluorooctyl bromide (PFOB) dual-layer nanopolymersomes bearing indocyanine green (ICG) and camptothecin (CPT), named MICFNS, were developed in this study, and melanoma was exploited as the model for MICFNS manufacture and therapeutic application. Our data showed that MICFNS were able to stabilize both ICG and CPT in the nanocarriers and can be quickly internalized by B16F10 cells due to melanoma membrane-mediated homology. Upon NIR irradiation, MICFNS can trigger hyperthermia and offer enhanced singlet oxygen production due to the incorporation of PFOB. With ≥10/2.5 µM ICG/CPT, MICFNS + NIR can provide comparable in vitro cancericidal effects to those caused by using an 8-fold higher dose of encapsulated CPT alone. Through the animal study, we further demonstrated that MICFNS can be quickly brought to tumors and have a longer retention time than those of free agents in vivo. Moreover, the MICFNS with 40/10 µM ICG/CPT in combination with 30 s NIR irradiation can successfully inhibit tumor growth without systemic toxicity in mice within the 14 day treatment. We speculate that such an antitumoral effect was achieved by phototherapy followed by chemotherapy, a two-stage tumoricidal process performed by MICFNS. Taken together, we anticipate that MICFNS, a photochemotherapeutic nanoplatform, has high potential for use in clinical anticancer treatment.

Genetic biomarker prediction based on gender disparity in asthma throughout machine learning.

Background: Asthma is a chronic respiratory condition affecting populations worldwide, with prevalence ranging from 1-18% across different nations. Gender differences in asthma prevalence have attracted much attention. Purpose: The aim of this study was to investigate biomarkers of gender differences in asthma prevalence based on machine learning. Method: The data came from the gene expression omnibus database (GSE69683, GSE76262, and GSE41863), which involved in a number of 575 individuals, including 240 males and 335 females. Theses samples were divided into male group and female group, respectively. Grid search and cross-validation were employed to adjust model parameters for support vector machine, random forest, decision tree and logistic regression model. Accuracy, precision, recall, and F1 score were used to evaluate the performance of the models during the training process. After model optimization, four machine learning models were utilized to predict biomarkers of sex differences in asthma. In order to validate the accuracy of our results, we performed Wilcoxon tests on the genes expression. Result: In datasets GSE76262 and GSE69683, support vector machine, random forest, logistic regression, and decision tree all achieve 100% accuracy, precision, recall, and F1 score. Our findings reveal that XIST serves as a common biomarker among the three samples, comprising a total of 575 individuals, with higher expression levels in females compared to males (p < 0.01). Conclusion: XIST serves as a genetic biomarker for gender differences in the prevalence of asthma.

PDIA3 defines a novel subset of adipose macrophages to exacerbate the development of obesity and metabolic disorders.

Adipose tissue macrophages (ATMs) play important roles in maintaining adipose tissue homeostasis and orchestrating metabolic inflammation. Given the extensive functional heterogeneity and phenotypic plasticity of ATMs, identification of the authentically pathogenic ATM subpopulation under obese setting is thus necessitated. Herein, we performed single-nucleus RNA sequencing (snRNA-seq) and unraveled a unique maladaptive ATM subpopulation defined as ATF4hiPDIA3hiACSL4hiCCL2hi inflammatory and metabolically activated macrophages (iMAMs), in which PDIA3 is required for the maintenance of their migratory and pro-inflammatory properties. Mechanistically, ATF4 serves as a metabolic stress sensor to transcribe PDIA3, which then imposes a redox control on RhoA activity and strengthens the pro-inflammatory and migratory properties of iMAMs through RhoA-YAP signaling. Administration of Pdia3 small interfering RNA (siRNA)-loaded liposomes effectively repressed adipose inflammation and high-fat diet (HFD)-induced obesity. Together, our data support that strategies aimed at targeting iMAMs by suppressing PDIA3 expression or activity could be a viable approach against obesity and metabolic disorders in clinical settings.

A comprehensive examination and meta-analysis evaluating perioperative, oncological, and functional results of robotic-assisted radical prostatectomy (RARP) in comparison to three-dimensional laparoscopic radical prostatectomy (3D LRP).

Assessing the perioperative, oncological, and functional results of robotic-assisted radical prostatectomy (RARP) versus three-dimensional laparoscopic radical prostatectomy (3D LRP), a comprehensive exploration of the Cochrane Library, PubMed, EMBASE, and Web of Science databases was carried out until July 2024. The combined results were evaluated by utilizing the weighted mean differences (WMDs) and odds ratios (ORs) through the application of Stata version 18, where data were gathered and scrutinized. In addition, sensitivity analyses were performed to ensure the robustness of our findings. In the meta-analysis we conducted, four studies were incorporated in total, which comprised two randomized controlled trials, one study that was retrospective and another that was prospective. The findings revealed that RARP was associated with a significantly reduced estimated blood loss (EBL) (WMD - 31.04, 95%CI - 54.57, - 7.51; p = 0.01) compared to 3D LRP. Nonetheless, there were no notable statistical variances seen between the two groups regarding operative time (OT), nerve-sparing rates, positive surgical margin (PSM) rates, biochemical recurrence (BCR) rates, or the restoration of urinary continence and potency 3 or 6 months after the surgery. In conclusion, our comprehensive meta-analysis has offered a detailed contrast between the results of RARP and 3D LRP in the treatment of prostate cancer. The findings highlight a considerable decrease in projected blood loss linked with RARP, yet no notable variances were detected between the two methods regarding other perioperative, oncological, and functional results.

Co-exposure to microplastics and soil pollutants significantly exacerbates toxicity to crops: Insights from a global meta and machine-learning analysis.

Environmental contamination of microplastics (MPs) is ubiquitous worldwide, and co-contamination of arable soils with MPs and other pollutants is of increasing concern, and may lead to unexpected consequences on crop production. However, the overall implications of this combined effect, whether beneficial or detrimental, remain a subject of current debate. Here, we conducted a global meta and machine-learning analysis to evaluate the effects of co-exposure to MPs and other pollutants on crops, utilizing 3346 biological endpoints derived from 68 different studies. Overall, compared with control groups that only exposure to conventional soil contaminants, co-exposure significantly exacerbated toxicity to crops, particularly with MPs intensifying adverse effects on crop morphology, oxidative damage, and photosynthetic efficiency. Interestingly, our analysis demonstrated a significant reduction in the accumulation of pollutants in the crop due to the presence of MPs. In addition, the results revealed that potential adverse effects were primarily associated with crop species, MPs mass concentration, and exposure duration. Our study reaffirms the substantial repercussions of MPs as emerging pollutants on crops within the context of integrated pollution, providing novel insights into improving sustainability in agro-ecosystems.

Perioperative, functional, and oncologic outcomes in obese patients undergoing Da Vinci robot-assisted radical prostatectomy: a systematic review and meta-analysis.

OBJECTIVE: The influence of robot-assisted radical prostatectomy (RARP) in obese (OB) and non-obese (NOB) prostate cancer patients remains a topic of debate. The objective of this study was to juxtapose the perioperative, functional, and oncologic outcomes of RARP in OB and NOB cohorts. MATERIALS AND METHODS: We systematically searched the databases such as PubMed, Embase, Web of Science, and the Cochrane Library database to identify relevant studies published in English up to September 2023. Review Manager was used to compare various parameters. The study was registered with PROSPERO (CRD42023473136). Sixteen comparative trials were included for 8434 obese patients compared with 55,266 non-obese patients. RESULTS: The OB group had a longer operative time (WMD 17.8 min, 95% CI 9.7,25.8; p < 0.0001), a longer length of hospital stay (WMD 0.18 day, 95% CI 0.12,0.24; p < 0.00001, a higher estimated blood loss (WMD 50.6 ml, 95% CI 11.7,89.6; p = 0.01), and higher pelvic lymphadenectomy rate (RR 1.08, 95% CI 1.04,1.12; p < 0.0001)and lower nerve sparing rate (RR 0.95, 95% CI 0.91,0.99; p < 0.01), but there was no difference between unilateral (RR 1.0, 95% CI 0.8,1.3; p = 0.8)and bilateral (RR 0.9, 95% CI 0.9,1.0; p = 0.06)nerve sparing rate. Then, complication rates (RR 1.6, 95% CI 1.5,1.7; p < 0.00001) were higher in the OB group, and both major (RR 1.4, 95% CI 1.1,1.8; p = 0.01)and minor (RR 1.4, 95% CI 1.1,1.7; p < 0.01)complication rates were higher in the OB group. Moreover, obese patients showed significantly higher probabilities of incontinence (RR 1.17, 95% CI 1.03,1.33; p = 0.01) and impotency (RR 1.08, 95% CI 1.01,1.15; p = 0.02) at 1 year. Last, the positive surgical margin (RR 1.2, 95% CI 1.1,1.3; p < 0.01) was higher in the OB group. CONCLUSION: In the obese group, perioperative outcomes, total complications, functional outcomes, and oncologic outcomes were all worse for RARP. Weight loss before RARP may be a feasible strategy to improve the prognosis of patients.

Nomogram predicting the prognosis of primary liver cancer after radiofrequency ablation combined with transcatheter arterial chemoembolization.

BACKGROUND: The incidence and mortality rates of primary hepatocellular carcinoma (HCC) are high, and the conventional treatment is radiofrequency ablation (RFA) with transcatheter arterial chemoembolization (TACE); however, the 3-year survival rate is still low. Further, there are no visual methods to effectively predict their prognosis. AIM: To explore the factors influencing the prognosis of HCC after RFA and TACE and develop a nomogram prediction model. METHODS: Clinical and follow-up information of 150 patients with HCC treated using RFA and TACE in the Hangzhou Linping Hospital of Traditional Chinese Medicine from May 2020 to December 2022 was retrospectively collected and recorded. We examined their prognostic factors using multivariate logistic regression and created a nomogram prognosis prediction model using the R software (version 4.1.2). Internal verification was performed using the bootstrapping technique. The prognostic efficacy of the nomogram prediction model was evaluated using the concordance index (CI), calibration curve, and receiver operating characteristic curve. RESULTS: Of the 150 patients treated with RFA and TACE, 92 (61.33%) developed recurrence and metastasis. Logistic regression analysis identified six variables, and a predictive model was created. The internal validation results of the model showed a CI of 0.882. The correction curve trend of the prognosis prediction model was always near the diagonal, and the mean absolute error before and after internal validation was 0.021. The area under the curve of the prediction model after internal verification was 0.882 [95% confidence interval (95%CI): 0.820-0.945], with a specificity of 0.828 and sensitivity of 0.656. According to the Hosmer-Lemeshow test, χ 2 = 3.552 and P = 0.895. The predictive model demonstrated a satisfactory calibration, and the decision curve analysis demonstrated its clinical applicability. CONCLUSION: The prognosis of patients with HCC after RFA and TACE is affected by several factors. The developed prediction model based on the influencing parameters shows a good prognosis predictive efficacy.

In-situ atomic tracking of intermetallic compound formation during thermal annealing.

Intermetallic compounds (IMCs) with ordered atomic structure have gained great attention as nanocatalysts for its enhanced activity and stability. Although the reliance of IMC preparation on high-temperature annealing is well known, a comprehensive understanding of the formation mechanisms of IMCs in this process is currently lacking. Here, we employ aberration-corrected high-angle annular dark-field scanning transmission electron microscopy (AC-HAADF-STEM) to track the formation process of IMCs on carbon supports during in-situ annealing, by taking PtFe as a case study within an industry-relevant impregnation synthesis framework. We directly discern five different stages at the atomic level: initial atomic precursors; Pt cluster formation; Pt-Fe disordered alloying; structurally ordered Pt3Fe formation, and final Pt3Fe-PtFe IMC conversion. In particular, we find that the crucial role of high-temperature annealing resides in facilitating the diffusion of Fe towards Pt, enabling the creation of alloys with the targeted stoichiometric ratio, which in turn provides the thermodynamic driving force for the disorder-to-order transition.

On the FT-ICR mass spectrometry analysis of dissolved organic matter released by adsorbent during coal chemical wastewater treatment.

This study analyzed the dissolved organic matter (DOM) released by adsorbent during wastewater treatment. It was found that the adsorption method resulted in an organic removal efficiency of over 97 % for coal-to-olefin (CTO) wastewater, with the lowest value of 15.7 mg/L. The Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR MS) detected 4111 DOM in the wastewater, 4052 remaining DOM after first-stage anthracite (ANC) adsorption, and 1013 after second-stage macroporous adsorption resin (MAR). The removal degree of lipids in wastewater was the highest, followed by aliphatic/amino-acid/mini-peptides and lignin. During the adsorption process, the proportion of halogenated compounds (HCs) declined from 59.86 % to 38.63 % and 21.67 %. Additionally, freshly produced 2035 and 311 DOMs were found in the adsorption effluent of ANC and MAR, respectively, with HCs accounting for 34.71 % and 67.96 %. Upon flowing ultra-pure water through ANC and MAR, the effluent dissolved organic carbon (DOC) ranges were 1.118-3.574 mg/L and 1.014-2.557 mg/L, respectively. There were 159 and 131 species of DOM detected, respectively, with HCs content of 59.06 % and 45.02 %. Comparative experiments revealed the complex components of the wastewater promoting the release of organic matter on the adsorbent surface that further reacted to generate organic matter. However, fewer substances were released by the adsorbent.

Oncoprotein-induced transcript 3 protein-enriched extracellular vesicles promotes NLRP3 ubiquitination to alleviate acute lung injury after cardiac surgery.

Acute lung injury (ALI) including acute respiratory distress syndrome (ARDS) is a major complication and increase the mortality of patients with cardiac surgery. We previously found that the protein cargoes enriched in circulating extracellular vesicles (EVs) are closely associated with cardiopulmonary disease. We aimed to evaluate the implication of EVs on cardiac surgery-associated ALI/ARDS. The correlations between "oncoprotein-induced transcript 3 protein (OIT3) positive" circulating EVs and postoperative ARDS were assessed. The effects of OIT3-overexpressed EVs on the cardiopulmonary bypass (CPB) -induced ALI in vivo and inflammation of human bronchial epithelial cells (BEAS-2B) were detected. OIT3 enriched in circulating EVs is reduced after cardiac surgery with CPB, especially with postoperative ARDS. The "OIT3 positive" EVs negatively correlate with lung edema, hypoxemia and CPB time. The OIT3-overexpressed EVs can be absorbed by pulmonary epithelial cells and OIT3 transferred by EVs triggered K48- and K63-linked polyubiquitination to inactivate NOD-like receptor protein 3 (NLRP3) inflammasome, and restrains pro-inflammatory cytokines releasing and immune cells infiltration in lung tissues, contributing to the alleviation of CPB-induced ALI. Overexpression of OIT3 in human bronchial epithelial cells have similar results. OIT3 promotes the E3 ligase Cbl proto-oncogene B associated with NLRP3 to induce the ubiquitination of NLRP3. Immunofluorescence tests reveal that OIT3 is reduced in the generation from the liver sinusoids endothelial cells (LSECs) and secretion in liver-derived EVs after CPB. In conclusion, OIT3 enriched in EVs is a promising biomarker of postoperative ARDS and a therapeutic target for ALI after cardiac surgery.

C3-Alkylation of Imidazo[1,2-a]pyridines via Three-Component Aza-Friedel-Crafts Reaction Catalyzed by Y(OTf)3.

As an important class of nitrogen-containing fused heterocyclic compounds, imidazo[1,2-a]pyridines often exhibit significant biological activities, such as analgesic, anticancer, antiosteoporosis, anxiolytic, etc. Using Y(OTf)3 as a Lewis acid catalyst, a simple and efficient method has been developed for the synthesis of C3-alkylated imidazo[1,2-a]pyridines through the three-component aza-Friedel-Crafts reaction of imidazo[1,2-a]pyridines, aldehydes, and amines in the normal air atmosphere without the protection of inert gas and special requirements for anhydrous and anaerobic conditions. A series of imidazo[1,2-a]pyridine derivatives were obtained with moderate to good yields, and their structures were confirmed by 1H NMR, 13C NMR, and HRMS. Furthermore, this conversion has the advantages of simple operation, excellent functional group tolerance, high atomic economy, broad substrate scope, and can achieve gram-level reactions. Notably, this methodology may be conveniently applied to the further design and rapid synthesis of potential biologically active imidazo[1,2-a]pyridines with multifunctional groups.

Fertilization regulates global thresholds in soil bacteria.

Global patterns in soil microbiomes are driven by non-linear environmental thresholds. Fertilization is known to shape the soil microbiome of terrestrial ecosystems worldwide. Yet, whether fertilization influences global thresholds in soil microbiomes remains virtually unknown. Here, utilizing optimized machine learning models with Shapley additive explanations on a dataset of 10,907 soil samples from 24 countries, we discovered that the microbial community response to fertilization is highly dependent on environmental contexts. Furthermore, the interactions among nitrogen (N) addition, pH, and mean annual temperature contribute to non-linear patterns in soil bacterial diversity. Specifically, we observed positive responses within a soil pH range of 5.2-6.6, with the influence of higher temperature (>15°C) on bacterial diversity being positive within this pH range but reversed in more acidic or alkaline soils. Additionally, we revealed the threshold effect of soil organic carbon and total nitrogen, demonstrating how temperature and N addition amount interacted with microbial communities within specific edaphic concentration ranges. Our findings underscore how complex environmental interactions control soil bacterial diversity under fertilization.

Harnessing Deep Learning for Accurate Pathological Assessment of Brain Tumor Cell Types.

Primary diffuse central nervous system large B-cell lymphoma (CNS-pDLBCL) and high-grade glioma (HGG) often present similarly, clinically and on imaging, making differentiation challenging. This similarity can complicate pathologists' diagnostic efforts, yet accurately distinguishing between these conditions is crucial for guiding treatment decisions. This study leverages a deep learning model to classify brain tumor pathology images, addressing the common issue of limited medical imaging data. Instead of training a convolutional neural network (CNN) from scratch, we employ a pre-trained network for extracting deep features, which are then used by a support vector machine (SVM) for classification. Our evaluation shows that the Resnet50 (TL + SVM) model achieves a 97.4% accuracy, based on tenfold cross-validation on the test set. These results highlight the synergy between deep learning and traditional diagnostics, potentially setting a new standard for accuracy and efficiency in the pathological diagnosis of brain tumors.

Structural Simplification of Podophyllotoxin: Discovery of γ-Butyrolactone Derivatives as Novel Antiviral Agents for Plant Protection.

Natural products are a valuable resource for the discovery of novel crop protection agents. A series of γ-butyrolactone derivatives, derived from the simplification of podophyllotoxin's structure, were synthesized and assessed for their efficacy against tobacco mosaic virus (TMV). Several derivatives exhibited notable antiviral properties, with compound 3g demonstrating the most potent in vivo anti-TMV activity. At 500 µg/mL, compound 3g achieved an inactivation effect of 87.8%, a protective effect of 71.7%, and a curative effect of 67.7%, surpassing the effectiveness of the commercial plant virucides ningnanmycin and ribavirin. Notably, the syn-diastereomer (syn-3g) exhibited superior antiviral activity compared to the anti-diastereomer (anti-3g). Mechanistic studies revealed that syn-3g could bind to the TMV coat protein and interfere with the self-assembly process of TMV particles. These findings indicate that compound 3g, with its simple chemical structure, could be a potential candidate for the development of novel antiviral agents for crop protection.

EGR3 Inhibits Tumor Progression by Inducing Schwann Cell-Like Differentiation.

The mechanism and function of the expression of Schwann characteristics by nevus cells in the mature zone of the dermis are unknown. Early growth response 3 (EGR3) induces Schwann cell-like differentiation of melanoma cells by simulating the process of nevus maturation, which leads to a strong phenotypic transformation of the cells, including the formation of long protrusions and a decrease in cell motility, proliferation, and melanin production. Meanwhile, EGR3 regulates the levels of myelin protein zero (MPZ) and collagen type I alpha 1 chain (COL1A1) through SRY-box transcription factor 10 (SOX10)-dependent and independent mechanisms, by binding to non-strictly conserved motifs, respectively. Schwann cell-like differentiation demonstrates significant benefits in both in vivo and clinical studies. Finally, a CD86-P2A-EGR3 recombinant mRNA vaccine is developed which leads to tumor control through forced cell differentiation and enhanced immune infiltration. Together, these data support further development of the recombinant mRNA as a treatment for cancer.

Wastewater Discharge Transports Riverine Microplastics over Long Distances.

Wastewater discharge from wastewater treatment plants continuously pumps microplastics into rivers, yet their transport distances within these waterways remain unknown. Herein, we developed a conceptual framework by synthesizing the microplastic data from the Yangtze River Basin to evaluate its transport distances, quantifying a significant spatial dependence between large-scale wastewater discharge and riverine microplastics (p < 0.05). The presence of microplastics at a specific sampling site could be attributed to wastewater discharge within a large-scale range spanning >1000 km upstream, encompassing a substantial portion equivalent to one-third of the Yangtze River Basin. The dominance analysis indicated that the contribution of wastewater discharge in rivers with higher discharge (>100 m3/s) to riverine microplastic pollution exceeded 65% within the Yangtze River Basin. The spatial dependence framework of riverine microplastics on wastewater discharge advances our prior understanding of the prevention and control of riverine microplastics by demonstrating that such pollution is not limited to nearby environmental factors.

Chronic oral administration of L-carnitine induces testicular injury: in vivo evidence.

PURPOSE: While L-carnitine is commonly used to treat oligoasthenozoospermia, concerns have been raised regarding its potential harm to spermatogenesis. This study aims to investigate the potential testicular toxicity of long-term oral administration of L-carnitine. METHODS: In this study, we refer to the clinical adult dosage and mode of L-carnitine administration, and after converting to mouse doses, mice were daily intragastrical administered L-carnitine to investigate whether it was harmful to the testis. The investigation involved assessing its potential testicular toxicity through histopathological staining, sperm motility analysis, and quantitative real-time PCR. RESULTS: Our results showed that L-carnitine increased sperm motility after 14 days of continuous administration, but increased luminal exfoliated spermatogenic cells occurred in the testis, and TUNEL results showed increased apoptotic cells. Compared with the control group, the mRNA expression of the spermatogenic cell marker at each stage was decreased in mice treated for 14 consecutive days of L-carnitine. After 50 days of continuous administration followed by 14 days of drug withdrawal, the total sperm motility of mice was almost 0, and a large number of abnormal eosinophilic spermatogenic cells appeared in the testis. These indicate that oral L-carnitine for more than 14 days impairs spermatogenesis in mice, and sudden discontinuation of administration results in substantial death of established spermatogenic cell populations. CONCLUSION: Our findings suggest that chronic oral administration of L-carnitine impairs spermatogenic function in the testis. The oral administration of L-carnitine to enhance sperm motility should not exceed the 2/5 point of the spermatogenic cycle.