PTPN23[Thr] variant reduces susceptibility and tumorigenesis in esophageal squamous cell carcinoma through dephosphorylation of EGFR.

Post-translational modifications (PTMs) have emerged as pivotal regulators of the development of cancers, including esophageal squamous cell carcinoma (ESCC). Here, we conducted a comprehensive analysis of PTM-related genetic variants associated with ESCC risk using large-scale genome-wide and exome-wide association datasets. We observed significant enrichment of PTM-related variants in the ESCC risk loci and identified five variants that were significantly associated with ESCC risk. Among them, rs6780013 in PTPN23 exhibited the highest level of significance in ESCC susceptibility in 9,728 ESCC cases and 10,977 controls (odds ratio [OR] = 0.85, 95 % confidence interval [CI] = 0.81- 0.89, P = 9.77 × 10-14). Further functional investigations revealed that PTPN23[Thr] variant binds to EGFR and modulates its phosphorylation at Thr699. PTPN23[Thr] variant substantially inhibited ESCC cell proliferation both in vitro and in vivo. Our findings underscore the critical role of PTPN23[Thr]-EGFR interaction in ESCC development, providing more insights into the pathogenesis of this cancer.

The 90% effective dose (ED90) of remimazolam for inhibiting responses to the insertion of a duodenoscope during ERCP.

BACKGROUND: Compared to midazolam, remimazolam has a faster onset and offset of hypnotic effect, as well as cardiorespiratory stability, this study aims to determine the 90% effective dose (ED90) of remimazolam to inhibit responses to insertion of a duodenoscope during endoscopic retrograde cholangiopancreatography (ERCP). METHODS: A dose-response study was carried out undergoing ERCP who received remimazolam-alfentanil anesthesia using 10 µg/kg of alfentanil between September 2021 and November 2021. The initial dose of remimazolam was 0.2 mg/kg. The dose was then decided based on the responses of earlier patients by exploiting the sequential ascend and descend according to a 9: 1 biased coin design. Upon failure, the dose of remimazolam was increased by 0.025 mg/kg in the next patient. When the insertion was successful, the succeeding patient was randomized to an identical dose or a dose that was lower by 0.025 mg/kg.The ED90 of remimazolam for inhibiting responses to the insertion of a duodenoscope during ERCP was calculated. Adverse events and complications of remimazolam were recorded. RESULTS: A total of 55 elderly patients (age > 65) were included in the study. 45 successfully anesthetized patients, and 10 unsuccessfully. The ED90 of remimazolam was 0.300 mg/kg (95% CI = 0.287-0.320). ED95 was 0.315 (95% CI = 0.312-0.323) and ED99 was 0.323 (95% CI = 0.323-0.325). Among the patients, 9 patients developed hypotension, 2 patients developed bradycardia and 1 patient developed tachycardia, and hypoxia occurred in 2 patients. CONCLUSIONS: A loading dose of 0.300 mg / kg of remimazolam for elderly patients undergoing ERCP can safely, effectively, and quickly induce patients to fall asleep and inhibit responses to the insertion of a duodenoscope. TRIAL REGISTRATION: The study protocol was registered at the website ClinicalTrials.gov on 22/09/2021(NCT05053763).

Influenza D virus infection in China, 2022-2023.

Influenza D virus (IDV) plays an important role in the bovine respiratory disease (BRD) complex. Its potential for the zoonotic transmission is of particular concern. In China, IDV has previously been identified in agricultural animals by molecular surveys with no live virus isolates reported. In this study, live IDVs were successfully isolated from cattle in China, which prompted us to further investigate the national prevalence, antigenic property, and infection biology of the virus. IDV RNA was detected in 11.1% (51/460) of cattle throughout the country in 2022-2023. Moreover, we conducted the first IDV serosurveillance in China, revealing a high seroprevalence (91.4%, 393/430) of IDV in cattle during the 2022-2023 winter season. Notably, all the 16 provinces from which cattle originated possessed seropositive animals, and 3 of them displayed the 100% IDV-seropositivity rate. In contrast, a very low seroprevalence of IDV was observed in pigs (3%, 3/100) and goats (1%, 1/100) during the same period of investigation. Furthermore, besides D/Yama2019 lineage-like IDVs, we discovered the D/660 lineage-like IDV in Chinese cattle, which has not been detected to date in Asia. Finally, the Chinese IDVs replicated robustly in diverse cell lines but less efficiently in the swine cell line. Considering the nationwide distribution, high seroprevalence, and appreciably genetic diversity, further studies are required to fully evaluate the risk of Chinese IDVs for both animal and human health in China, which can be evidently facilitated by IDV isolates reported in this study.

Characteristics of gut microbiota and its correlation with hs-CRP and somatic symptoms in first-episode treatment-naive major depressive disorder.

OBJECTIVE: Most patients with major depressive disorder (MDD) have somatic symptoms, but little studies pay attention in the microbial-inflammatory mechanisms of these somatic symptoms. Our study aimed to investigate alterations in gut microbiota and its correlation with inflammatory marker levels and somatic symptoms in first-episode treatment-naive MDD. METHODS: Subjects contained 160 MDD patients and 101 healthy controls (HCs). MDD patients were divided into MDD with somatic symptoms group (MDDS) and MDD without somatic symptoms group (MDDN) based on Somatic Self-rating Scale (SSS). 16S ribosomal RNA sequencing were performed to analyze the composition of the fecal microbiota. The inflammatory factors were measured using enzyme linked immunosorbent assay (ELISA). Correlation among the altered gut microbiota, inflammatory factor and severity of clinical symptoms were analysized. RESULTS: Relative to HCs, MDD patients had higher levels of high-sensitivity C-reactive protein (hs-CRP) as well as disordered α-diversity and ß-diversity of gut microbiota. Linear discriminant effect size (LEfSe) analysis showed that MDD patients had higher proportions of Bifidobacterium, Blautia, Haemophilus and lower proportions of Bacteroides, Faecalibacterium, Roseburia, Dialister, Sutterella, Parabacteroides, Bordetella, and Phascolarctobacterium from the genus aspect. Furthermore, correlation analysis showed Bacteroides and Roseburia had negative correlations with the hs-CRP, HAMD-24, the total and factor scores of SSS in all participants. Further, compared with MDDN, the Pielous evenness was higher in MDDS. Random Forest (RF) analysis showed 20 most important genera discriminating MDD-S and MDDN, HCs. The ROC analysis showed that the AUC was 0.90 and 0.81 combining these genera respectively. CONCLUSION: Our study manifested MDD patients showed disordered gut microbiota and elevated hs-CRP levels, and altered gut microbiota was closely associated with hs-CRP, depressive symptoms, and somatic symptoms.

Phytoplankton-derived polysaccharides and microbial peptidoglycans are key nutrients for deep-sea microbes in the Mariana Trench.

BACKGROUND: The deep sea represents the largest marine ecosystem, driving global-scale biogeochemical cycles. Microorganisms are the most abundant biological entities and play a vital role in the cycling of organic matter in such ecosystems. The primary food source for abyssal biota is the sedimentation of particulate organic polymers. However, our knowledge of the specific biopolymers available to deep-sea microbes remains largely incomplete. One crucial rate-limiting step in organic matter cycling is the depolymerization of particulate organic polymers facilitated by extracellular enzymes (EEs). Therefore, the investigation of active EEs and the microbes responsible for their production is a top priority to better understand the key nutrient sources for deep-sea microbes. RESULTS: In this study, we conducted analyses of extracellular enzymatic activities (EEAs), metagenomics, and metatranscriptomics from seawater samples of 50-9305 m from the Mariana Trench. While a diverse array of microbial groups was identified throughout the water column, only a few exhibited high levels of transcriptional activities. Notably, microbial populations actively transcribing EE genes involved in biopolymer processing in the abyssopelagic (4700 m) and hadopelagic zones (9305 m) were primarily associated with the class Actinobacteria. These microbes actively transcribed genes coding for enzymes such as cutinase, laccase, and xyloglucanase which are capable of degrading phytoplankton polysaccharides as well as GH23 peptidoglycan lyases and M23 peptidases which have the capacity to break down peptidoglycan. Consequently, corresponding enzyme activities including glycosidases, esterase, and peptidases can be detected in the deep ocean. Furthermore, cell-specific EEAs increased at 9305 m compared to 4700 m, indicating extracellular enzymes play a more significant role in nutrient cycling in the deeper regions of the Mariana Trench. CONCLUSIONS: Transcriptomic analyses have shed light on the predominant microbial population actively participating in organic matter cycling in the deep-sea environment of the Mariana Trench. The categories of active EEs suggest that the complex phytoplankton polysaccharides (e.g., cutin, lignin, and hemicellulose) and microbial peptidoglycans serve as the primary nutrient sources available to deep-sea microbes. The high cell-specific EEA observed in the hadal zone underscores the robust polymer-degrading capacities of hadal microbes even in the face of the challenging conditions they encounter in this extreme environment. These findings provide valuable new insights into the sources of nutrition, the key microbes, and the EEs crucial for biopolymer degradation in the deep seawater of the Mariana Trench. Video Abstract.

Effects of extracorporeal diaphragm pacing combined with inspiratory muscle training on respiratory function in people with stroke: a randomized controlled trial.

OBJECTIVES: To evaluate the effect of external diaphragmatic pacing (EDP) combined with inspiratory muscle training on respiratory function in post-stroke patients. METHODS: Patients with stroke were enrolled from the First Affiliated Hospital of Soochow University in China between 2021 and 2022. The patients were randomized into an EDP treatment group (control group) or an EDP treatment plus inspiratory muscle training group (experimental group). Each therapy was administered once a day for 6 days per week. The peak inspiratory flow (PIF), maximal inspiratory pressure (MIP), forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC% ratio, and diaphragm thickness and mobility were measured and compared between the two groups after 4 weeks. RESULTS: After 4 weeks of intervention, respiratory muscle function indicators including PIF (95% CI: 0.21-1.28, p = 0.008) and MIP (95% CI: 6.92-25.44, p = 0.001) significantly improved in the experimental group. Diaphragmatic thickness also significantly increased in the experimental group (p < 0.05), while diaphragmatic excursion showed no significant difference between the two groups. Additionally, FVC (95% CI: 0.14-1.14, p = 0.013) and FEV1 (95% CI: 0.20-1.06, p = 0.005) demonstrated a significant increase in the experimental group, whereas FEV1/FVC% (95% CI: -0.84 to 9.36, p = 0.099) exhibited no significant group difference. CONCLUSION: EDP combined with inspiratory muscle training in individuals with stroke provides greater benefits than EDP alone in terms of respiratory function recovery, except for the parameters of diaphragmatic excursion and FEV1/FVC%.

Models of the Three-Component Bilayer of Stratum Corneum: A Molecular Simulation Study.

The construction of the stratum corneum (SC) is crucial to the problems of transdermal drug delivery. SC consists of the keratinocyte layers and the lipid matrix surrounding it. Among them, the lipid matrix is the barrier for many exogenous molecules, mainly composed of ceramides (CERs), free fatty acids (FFA), and cholesterol (CHOL). In this work, we developed single-component (CERs, CER-NS, and CER-EOS) and six three-component models, and each model was simulated by using the GROMOS-54A7 force field. Short-period phase (SPP) and long-period phase (LPP) systems were established separately, and area per lipid (APL), thickness, order of carbon chain (SCD), and density distribution were analyzed. The transition of CER-NS and CER-EOS in LPP was observed. The results of hydrogen bonds in the lipid systems indicated that a strong hydrogen-bond network was formed between the skin-lipid bilayers. Umbrella sampling method simulations were performed to calculate the free energy change of ethanol moving into the skin-lipid bilayer. The results revealed that ethanol molecules pulled some water molecules into the membrane when they passed through SPP-1. Our findings provided some insights and models of the stratum corneum that could be used for the subsequent mechanism of macromolecule permeation through membranes in drugs, cosmetics, and so on.

CCR5 and inflammatory storm.

Chemokines and their corresponding receptors play crucial roles in orchestrating inflammatory and immune responses, particularly in the context of pathological conditions disrupting the internal environment. Among these receptors, CCR5 has garnered considerable attention due to its significant involvement in the inflammatory cascade, serving as a pivotal mediator of neuroinflammation and other inflammatory pathways associated with various diseases. However, a notable gap persists in comprehending the intricate mechanisms governing the interplay between CCR5 and its ligands across diverse and intricate inflammatory pathologies. Further exploration is warranted, especially concerning the inflammatory cascade instigated by immune cell infiltration and the precise binding sites within signaling pathways. This study aims to illuminate the regulatory axes modulating signaling pathways in inflammatory cells by providing a comprehensive overview of the pathogenic processes associated with CCR5 and its ligands across various disorders. The primary focus lies on investigating the pathomechanisms associated with CCR5 in disorders related to neuroinflammation, alongside the potential impact of aging on these processes and therapeutic interventions. The discourse culminates in addressing current challenges and envisaging potential future applications, advocating for innovative research endeavors to advance our comprehension of this realm.

Promotion of levoglucosan production from biomass pyrolysis by hydrogen peroxide pre-oxidation.

Due to the complexity of biomass structures, the conversion of raw biomass into value-added chemicals is challenging and often requires efficient pretreatment of the biomass. In this paper, a simple and green pre-oxidation method, which was conducted under the conditions of 2 wt% H2O2, 80 min, and 150 °C, was reported to significantly increase the production of levoglucosan (LG) from biomass pyrolysis. The result showed that the LG yield significantly increased from 2.3 wt% (without pre-oxidation) to 23.1 wt% when pine wood was employed as a sample for pyrolysis at 400 °C, resulting from the removal of hemicellulose fraction and the in-situ acid catalysis of lignin carboxyl groups formed during the pre-oxidation. When the conditions for pre-oxidation became harsher than the above, the LG yield reduced because the decomposition of cellulose fraction in biomass. The study supplies an effective method for utilization of biomass as chemicals.

Targeting metabolism to improve CAR-T cells therapeutic efficacy.

ABSTRACT: Chimeric antigen receptor T (CAR-T) cell therapy achieved advanced progress in the treatment of hematological tumors. However, the application of CAR-T cell therapy for solid tumors still faces many challenges. Competition with tumor cells for metabolic resources in an already nutrient-poor tumor microenvironment is a major contributing cause to CAR-T cell therapy's low effectiveness. Abnormal metabolic processes are now acknowledged to shape the tumor microenvironment, which is characterized by increased interstitial fluid pressure, low pH level, hypoxia, accumulation of immunosuppressive metabolites, and mitochondrial dysfunction. These factors are important contributors to restriction of T cell proliferation, cytokine release, and suppression of tumor cell-killing ability. This review provides an overview of how different metabolites regulate T cell activity, analyzes the current dilemmas, and proposes key strategies to reestablish the CAR-T cell therapy's effectiveness through targeting metabolism, with the aim of providing new strategies to surmount the obstacle in the way of solid tumor CAR-T cell treatment.

The potential effects of N-Acyl homoserine lactones on aerobic sludge granulation during phenolic wastewater treatment.

The formation of aerobic granular sludge (AGS) is relatively difficult during the treatment of refractory wastewater, which generally shows small granular sizes and poor stability. The formation of AGS is regulated by N-Acyl homoserine lactones (AHLs)-mediated quorum sensing (QS). However, the potential role of AHLs in AGS formation under the toxic stress of refractory pollutants and the heterogeneity in the distribution and function of AHLs across different aggregates are not well understood. This study investigated the potential effects of AHLs on the formation of AGS during phenolic wastewater treatment. The distribution and succession of AHLs across varying granular sizes and development stages of AGS were investigated. Results showed that AGS was successfully formed in 13 days with an average granular size of 335 ± 39 µm and phenol removal efficiency of >99%. The levels of AHLs initially increased and then decreased. C4-HSL and 3-oxo-C10-HSL were enriched in large granules, suggesting they may play a pivotal role in regulating the concentration and composition of extracellular polymeric substances (EPS). The content of EPS constantly increased to 149.4 mg/gVSS, and protein (PN) was enriched in small and large granules. Luteococcus was the dominant genus constituting up to 62% after the granulation process, and exhibited a strong association with C4-HSL. AHLs might also regulate the bacterial community responsible for EPS production, and pollutant removal, and facilitate the proliferation of slow-growing microorganisms, thereby enhancing the formation of AGS. The synthesis and dynamics of AHLs were mainly governed by AHLs-producing bacterial strains of Rhodobacter and Pseudomonas, and AHLs-quenching strains of Flavobacterium and Comamonas. C4-HSL and 3-oxo-C10-HSL might be the major contributors to promoting sludge granulation under phenol stress and play critical roles in large granules. These findings enhance our understanding of the roles that AHLs play in sludge granulation under toxic conditions.

Analysis of risk factors and interactions for pain in temporomandibular disorder: A cross-sectional study.

BACKGROUND: Risk factors for temporomandibular disorder (TMD) pain remain unclear. OBJECTIVES: This study aimed to identify risk factors for TMD pain using a biopsychosocial model and to investigate interactions between potential risk factors-oral behaviours (OBs), psychological factors and sleep quality-and their direct and indirect effects on TMD pain. METHODS: This was a cross-sectional study of 488 patients with TMDs (422 women; 30.8 ± 9.4 years). Pain was assessed using the Numerical Rating Scale. Demographic, behavioural, psychological and biomedical data were collected through clinical examination, face-to-face interviews and questionnaires. Multiple linear regression analysis was used to identify factors associated with TMD pain. Mediation and moderation analysis were used to evaluate interactions between variables. Significant mediation ('0' not included in the 95% confidence interval (CI)) and moderation (p < .05) effects on TMD pain were identified. RESULTS: Marital status, diagnosis subgroup, previous medication use, depression and sleep quality were significant risk factors for TMD pain (p < .05). Significant mediation effects were observed as follows: depression and sleep quality mediated the association between OBs and pain; sleep quality mediated the association between somatization, depression, anxiety and pain; and depression mediated the association between sleep quality and pain (all 95% CI did not contain '0'). CONCLUSIONS: (1) Marital status, diagnosis subgroup, previous medication use, depression and sleep quality were associated with TMD pain. (2) OBs can exacerbate pain by promoting depression and reducing sleep quality. Psychological factors and sleep quality can interact to exacerbate pain.

Zwitterionic Tröger's Base Microfiltration Membrane Prepared via Vapor-Induced Phase Separation with Improved Demulsification and Antifouling Performance.

The fouling of separation membranes has consistently been a primary factor contributing to the decline in membrane performance. Enhancing the surface hydrophilicity of the membrane proves to be an effective strategy in mitigating membrane fouling in water treatment processes. Zwitterionic polymers (containing an equimolar number of homogeneously distributed anionic and cationic groups on the polymer chains) have been used extensively as one of the best antifouling materials for surface modification. The conventional application of zwitterionic compounds as surface modifiers is intricate and inefficient, adding complexity and length to the membrane preparation process, particularly on an industrial scale. To overcome these limitations, zwitterionic polymer, directly used as a main material, is an effective method. In this work, a novel zwitterionic polymer (TB)-zwitterionic Tröger's base (ZTB)-was synthesized by quaternizing Tröger's base (TB) with 1,3-propane sultone. The obtained ZTB is blended with TB to fabricate microfiltration (MF) membranes via the vapor-induced phase separation (VIPS) process, offering a strategic solution for separating emulsified oily wastewater. Atomic force microscopy (AFM), scanning electron microscopy (SEM), water contact angle, and zeta potential measurements were employed to characterize the surface of ZTB/TB blended membranes, assessing surface morphology, charge, and hydrophilic/hydrophobic properties. The impact of varying ZTB levels on membrane surface morphology, hydrophilicity, water flux, and rejection were investigated. The results showed that an increase in ZTB content improved hydrophilicity and surface roughness, consequently enhancing water permeability. Due to the attraction of water vapor, the enrichment of zwitterionic segments was enriched, and a stable hydration layer was formed on the membrane surface. The hydration layer formed by zwitterions endowed the membrane with good antifouling properties. The proposed mechanism elucidates the membrane's proficiency in demulsification and the reduction in irreversible fouling through the synergistic regulation of surface charge and hydrophilicity, facilitated by electrostatic repulsion and the formation of a hydration layer. The ZTB/TB blended membranes demonstrated superior efficiency in oil-water separation, achieving a maximum flux of 1897.63 LMH bar-1 and an oil rejection rate as high as 99% in the oil-water emulsion separation process. This study reveals the migration behavior of the zwitterionic polymer in the membrane during the VIPS process. It enhances our comprehension of the antifouling mechanism of zwitterionic membranes and provides guidance for designing novel materials for antifouling membranes.

Transcriptomics analyses of IL-1ß-stimulated rat chondrocytes in temporomandibular joint condyles and effect of platelet-rich plasma.

The biological mechanism of action of platelet-rich plasma (PRP) in the treatment of temporomandibular joint (TMJ) osteoarthritis remains unclear. This study explored the mechanisms underlying interleukin (IL)-1ß-induced inflammation and investigated the effect of PRP on TMJ condylar chondrocytes. Primary chondrocytes were isolated from the TMJ condyle of 4-week-old rats, and differentially expressed genes among three treatment groups (phosphate-buffered saline [control], IL-1ß, and IL-1ß + PRP) were identified using RNA-seq and characterized using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes path-enrichment analyses. IL-1ß caused inflammatory injury to chondrocytes by upregulating the TNF, NF-κB, and IL-17 signaling pathways and downregulating the MAPK and PI3K/Akt signaling pathways. PRP activated the MAPK and PI3K/Akt signaling pathways, exerting a protective effect on IL-1ß-induced chondrocytes. PRP also activated the TNF and IL-17 signaling pathways, producing an inflammatory effect. Additionally, PRP increased the mRNA expression of the matrix catabolism-related genes Mmp3, Mmp9, and Mmp13; the proliferative markers Mki67 and PCNA; and the anti-apoptotic genes of the Bcl-2 family (Bcl2a1 and Bok), while reducing the expression of the pro-apoptotic genes Casp4 and Casp12. The findings suggest that the protective effect of PRP on IL-1ß-induced chondrocyte injury is mainly achieved via MAPK-PI3K/Akt signaling, increasing cell proliferation and inhibiting cell apoptosis.

Influence of para-substituted benzaldehyde derivatives with different push/pull electron strength groups on the conformation of human serum albumin and toxicological effects in zebrafish.

Excessive intake of benzaldehyde and its derivatives can cause irreversible damage to living organisms. Hence, benzaldehyde derivatives with different para-substitutions of push/pull electronic groups were chosen to investigate the effect of different substituent properties on the structure of human serum albumin (HSA). The binding constants, number of binding sites, major interaction forces, protein structural changes, and binding sites of benzaldehyde (BzH) and its derivatives (4-BzHD) with HSA in serum proteins were obtained based on multispectral and molecular docking techniques. The mechanism of BzH/4-BzHD interaction on HSA is mainly static quenching and is accompanied by the formation of a ground state complex. BzH/4-BzHD is bound to HSA in a 1:1 stoichiometric ratio. The interaction forces for the binding of BzH/4-BzHD to HSA are mainly hydrogen bonding and hydrophobic interaction, which are also accompanied by a small amount of electrostatic interactions. The effect of BzH/4-BzHD on HSA conformation follows: 4-Diethylaminobenzaldehyde (4-DBzH) > 4-Nitrobenzaldehyde (4-NBzH) > 4-Hydroxybenzaldehyde (4-HBzH) > 4-Acetaminobenzaldehyde (4-ABzH) > BzH, which means that the stronger push/pull electronic strength of the para-substituted benzaldehyde derivatives has a greater effect on HSA conformation. Furthermore, the concentration-lethality curves of different concentrations for BzH/4-BzHD on zebrafish verified above conclusion. This work provides a scientific basis for the risk assessment of benzaldehyde and its derivatives to the ecological environment and human health and for the environmental toxicological studies of benzaldehyde derivatives with different strengths of push/pull electron substitution.

Fabrication of crown ether-containing copolymer porous membrane and their enhanced adsorption performance for cationic dyes: Experimental and DFT investigations.

Adsorptive separation membranes are widely utilized for the removal of toxic dyeing pollutants from dyeing wastewater. However, developing novel adsorption membranes with large adsorption capacities and enhanced adsorption performance for dyes in actual wastewater poses a significant challenge. This study focuses on the fabrication of crown ether-containing copolymer porous membrane (CRPM) and investigation of the adsorption performance of dyes from aqueous solutions. The morphology structure and pore size distribution revealed that the membrane was endowed with rich micropores and hierarchical porous structures. Three typical cationic dyes (MB, RhB, CV) and an anionic dye (MO) were selected to evaluate the adsorption behavior. The results of adsorption isotherms and kinetics demonstrated that the adsorption data could be well-fitted using the Freundlich and pseudo-first-order kinetic models, the thermodynamic parameters revealed that the adsorption process of dyes on CRPM is a spontaneous endothermic reaction. The membrane exhibited excellent adsorption performance for cationic dyes, with RhB displaying a higher maximum adsorption capacity than previously reported porous membranes. Notably, dynamic adsorption-desorption filtration demonstrated a rapid removal efficiency, with RhB, MB, and CV achieving removal rates of 99.09%, 98.63%, and 99.14% respectively, after five cycles. The filtration volume of the CRPM membrane was 2.4-fold greater than that of a traditional PVDF membrane when applied to actual dyeing wastewater. DFT theoretical calculations were employed to elucidate the adsorption mechanism. These calculations confirmed the significant roles of electrostatic interactions, H-bonds and π-π interactions in facilitating the high-efficiency adsorption of cationic dyes. These findings highlight the potential of the crown ether-containing copolymer as a promising material for adsorption separation membranes in the treatment of dyeing wastewater.

IL-24 improves efficacy of CAR-T cell therapy by targeting stemness of tumor cells.

BACKGROUND: Cancer stem cells (CSCs) induce therapeutic resistance and may be an important barrier to cancer immunotherapy. Chimeric antigen receptor T (CAR-T) cell therapy has demonstrated remarkable efficacy in clinical settings. However, CAR-T cell therapy fails in a large proportion of patients, especially in those with solid tumors. It is unclear how CSCs mediate resistance to CAR-T cells, and whether CAR-T cells can more effectively eradicate CSCs. METHODS: In this study, the effect of CSCs on CAR-T cell therapy was determined using in vitro and in vivo assays. Subsequently, Interleukin-24 (IL-24) was expressed along with CAR in T cells. Further in vitro and in vivo tests were performed to determine the effects of IL-24 on CSCs and CAR-T cell therapy. RESULTS: IL-24 induced apoptosis in CSCs and contributed to T cell activation, differentiation, and proliferation. CAR.IL-24-T cells inhibited CSC enrichment and exhibited stronger antitumor activity in vitro and in vivo. CONCLUSIONS: IL-24 helps eliminate CSCs and endows CAR-T cells with improved antitumor reactivity.

Single-cell analysis identified POSTN+ cells associated with the aggressive phenotype and risk of esophageal squamous cell carcinoma.

Tumors are intricate and heterogeneous systems characterized by mosaic cancer cell populations with diverse expression profiles. Leveraging single-cell technologies, we employed the Scissor algorithm to delineate an epithelial subpopulation associated with the aggressive phenotype in esophageal squamous cell carcinoma (ESCC). This identified subpopulation exhibited elevated expression of genes involved in critical pathways, such as epithelial-mesenchymal transition and PI3K-Akt. Key signature genes within this subpopulation, namely CAV1, COL3A1, COL6A1, POSTN, and TAGLN, demonstrated significant upregulation concomitant with both tumorigenesis and tumor progression across independent single-cell datasets. Furthermore, we selected 1,450 expression quantitative trait loci of the top 62 signature genes of this cell subpopulation to investigate their potential in predicting ESCC risk. The results showed that the POSTN loci were predominantly associated with ESCC susceptibility. Through functional annotation and replication analyses, we identified that the rs1028728 in the POSTN promoter was significantly associated with increased ESCC risk in 7,049 ESCC cases and 8,063 controls (odds ratio = 1.29, 95% confidence interval: 1.18-1.42, p = 4.03 × 10-8). Subsequent biochemical experiments showed that the rs1028728[T] allele enhanced POSTN expression by affecting the binding of PRRX1 in the POSTN promoter. In summary, our meticulous single-cell analysis delineates an invasive epithelial subpopulation in ESCC, with POSTN emerging as an important marker for the aggressive phenotype. These findings offer more insights into potential strategies for the prevention and intervention of ESCC, enriching our understanding of this complex cancer landscape.

Response of C:N:P stoichiometry to long-term drainage of peatlands: Evidence from plant, soil, and enzyme.

Drought induced by climate warming and human activities regulates carbon (C) cycling of peatlands by changing plant community composition and soil properties. Estimating the responses of peatlands C cycling to environmental changes requires further study of C: nitrogen (N): phosphorus (P) stoichiometric ratios of soil, plants, and enzyme activities. However, systematic studies on the stoichiometry of above-ground and below-ground ecosystems of peatlands post drainage remain scarce. This study compared stoichimetric ratios of plant and soil and stoichimetric ratios of enzyme activities with different functions in two different parts of a minerotrophic peatland, a natural undisturbed part and a part that had been drained for almost 50 years, in Northern China. For the shrub plants, the average C:N:P ratios of leaf in natural and drained peatland were 448:17:1 and 393:15:1, respectively. This indicated that the growth rate of shrub plants is higher in the drained peatland than in the natural peatland, which makes P element more concentrated in the photosynthetic site. However, from the perspective of the dominant plant, the mean C:N:P ratio of Carex leaf was 650:25:1 in the natural peatland, but was 1028:50:1 for Dasiphora fruticosa in drained peatland. This indicated that the intensification of P-limitation of plant growth after drainage. Soil C:N:P ratios of above water table depth (AWT) were 238:15:1 and 277:12:1, but were 383:17:1 and 404:19:1 for below water table depth (BWT) in the natural and the drained peatland, respectively. Soil C:P ratios were greater than the threshold elemental ratio of C:P (174:1), but the soil C:N ratios were less than the threshold elemental ratio of C:N (23:1), which suggested that P was the most limiting nutrient of soil. The soil microbial activities were co-limited by C&P in Baijianghe peatlands. However, the microbial metabolic P limitation was intensified, but the C limitation was weakened for the above water table depth soil after long-term drainage. There are connection between plant-microbe P limitation in peatlands. The P limitation of microbial metabolism was significant positively correlated with soil C:N but negatively with soil moisture. The increase in the lignocelluloses index suggested considerable decomposition of soil organic matter after peatland drainage. These results of stoichiometric ratios from above- to below ground could provide scientific base for the C cycling of peatland undergone climate change.

The role of extracellular vesicles in COPD and potential clinical value.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous lung disease and a major health burden worldwide. Extracellular vesicles (EVs) are nanosized vesicles which possess a lipid bilayer structure that are secreted by various cells. They contain a variety of bioactive substances, which can regulate various physiological and pathological processes and are closely related to the development of diseases. Recently, EVs have emerged as a novel tool for intercellular crosstalk, which plays an essential role in COPD development. This paper reviews the role of EVs in the development of COPD and their potential clinical value, in order to provide a reference for further research on COPD.