Evaluation of Antioxidant Activity and Treatment of Eczema by Berberine Hydrochloride-Loaded Liposomes-in-Gel.

In this paper, berberine hydrochloride-loaded liposomes-in-gel were designed and developed to investigate their antioxidant properties and therapeutic effects on the eczema model of the mouse. Berberine hydrochloride-liposomes (BBH-L) as the nanoparticles were prepared by the thin-film hydration method and then dispersed BBH-L evenly in the gel matrix to prepare the berberine hydrochloride liposomes-gel (BBH-L-Gel) by the natural swelling method. Their antioxidant capacity was investigated by the free radical scavenging ability on 2,2-diphenyl-1-picrylhydrazyl (DPPH) and H2O2 and the inhibition of lipid peroxides malondialdehyde (MDA). An eczema model was established, and the efficacy of the eczema treatment was preliminarily evaluated using ear swelling, the spleen index, and pathological sections as indicators. The results indicate that the entrapment efficiency of BBH-L prepared by the thin-film hydration method was 78.56% ± 0.7%, with a particle size of 155.4 ± 9.3 nm. For BBH-L-Gel, the viscosity and pH were 18.16 ± 6.34 m Pas and 7.32 ± 0.08, respectively. The cumulative release in the unit area of the in vitro transdermal study was 85.01 ± 4.53 µg/cm2. BBH-L-Gel had a good scavenging capacity on DPPH and H2O2, and it could effectively inhibit the production of hepatic lipid peroxides MDA in the concentration range of 0.4-2.0 mg/mL. The topical application of BBH-L-Gel could effectively alleviate eczema symptoms and reduce oxidative stress injury in mice. This study demonstrates that BBH-L-Gel has good skin permeability, excellent sustained release, and antioxidant capabilities. They can effectively alleviate the itching, inflammation, and allergic symptoms caused by eczema, providing a new strategy for clinical applications in eczema treatment.

Selective adsorption of Cr(VI) by nitrogen-doped hydrothermal carbon in binary system.

Selective adsorption of heavy metal ions from industrial effluent is important for healthy ecosystem development. However, the selective adsorption of heavy metal pollutants by biochar using lignin as raw material is still a challenge. In this paper, the lignin carbon material (N-BLC) was synthesized by a one-step hydrothermal carbonization method using paper black liquor (BL) as raw material and triethylene diamine (TEDA) as nitrogen source. N-BLC (2:1) showed excellent selectivity for Cr(VI) in the binary system, and the adsorption amounts of Cr(VI) in the binary system were all greater than 150 mg/g, but the adsorption amounts of Ca(II), Mg(II), and Zn(II) were only 19.3, 25.5, and 6.3 mg/g, respectively. The separation factor (SF) for Cr(VI) adsorption was as high as 120.0. Meanwhile, FTIR, elemental analysis and XPS proved that the surface of N-BLC (2:1) contained many N- and O- containing groups which were favorable for the removal of Cr(VI). The adsorption of N-BLC (2:1) followed the Langmuir model and its maximum theoretical adsorption amount was 618.4 mg/g. After 5th recycling, the adsorption amount of Cr(VI) by N-BLC (2:1) decreased about 15%, showing a good regeneration ability. Therefore, N-BLC (2:1) is a highly efficient, selective and reusable Cr(VI) adsorbent with wide application prospects.

Single-cell profile reveals the landscape of cardiac immunity and identifies a cardio-protective Ym-1hi neutrophil in myocardial ischemia-reperfusion injury.

Myocardial ischemia-reperfusion injury (MIRI) is a major hindrance to the success of cardiac reperfusion therapy. Although increased neutrophil infiltration is a hallmark of MIRI, the subtypes and alterations of neutrophils in this process remain unclear. Here, we performed single-cell sequencing of cardiac CD45+ cells isolated from the murine myocardium subjected to MIRI at six-time points. We identified diverse types of infiltrating immune cells and their dynamic changes during MIRI. Cardiac neutrophils showed the most immediate response and largest changes and featured with functionally heterogeneous subpopulations, including Ccl3hi Neu and Ym-1hi Neu, which were increased at 6 h and 1 d after reperfusion, respectively. Ym-1hi Neu selectively expressed genes with protective effects and was, therefore, identified as a novel specific type of cardiac cell in the injured heart. Further analysis indicated that neutrophils and their subtypes orchestrated subsequent immune responses in the cardiac tissues, especially instructing the response of macrophages. The abundance of Ym-1hi Neu was closely correlated with the therapeutic efficacy of MIRI when neutrophils were specifically targeted by anti-Lymphocyte antigen 6 complex locus G6D (Ly6G) or anti-Intercellular cell adhesion molecule-1 (ICAM-1) neutralizing antibodies. In addition, a neutrophil subtype with the same phenotype as Ym-1hi Neu was detected in clinical samples and correlated with prognosis. Ym-1 inhibition exacerbated myocardial injury, whereas Ym-1 supplementation significantly ameliorated injury in MIRI mice, which was attributed to the tilt of Ym-1 on the polarization of macrophages toward the repair phenotype in myocardial tissue. Overall, our findings reveal the anti-inflammatory phenotype of Ym-1hi Neu and highlight its critical role in myocardial protection during the early stages of MIRI.

An Environment-Tolerant Ion-Conducting Double-Network Composite Hydrogel for High-Performance Flexible Electronic Devices.

High-performance ion-conducting hydrogels (ICHs) are vital for developing flexible electronic devices. However, the robustness and ion-conducting behavior of ICHs deteriorate at extreme temperatures, hampering their use in soft electronics. To resolve these issues, a method involving freeze-thawing and ionizing radiation technology is reported herein for synthesizing a novel double-network (DN) ICH based on a poly(ionic liquid)/MXene/poly(vinyl alcohol) (PMP DN ICH) system. The well-designed ICH exhibits outstanding ionic conductivity (63.89 mS cm-1 at 25 °C), excellent temperature resistance (- 60-80 °C), prolonged stability (30 d at ambient temperature), high oxidation resistance, remarkable antibacterial activity, decent mechanical performance, and adhesion. Additionally, the ICH performs effectively in a flexible wireless strain sensor, thermal sensor, all-solid-state supercapacitor, and single-electrode triboelectric nanogenerator, thereby highlighting its viability in constructing soft electronic devices. The highly integrated gel structure endows these flexible electronic devices with stable, reliable signal output performance. In particular, the all-solid-state supercapacitor containing the PMP DN ICH electrolyte exhibits a high areal specific capacitance of 253.38 mF cm-2 (current density, 1 mA cm-2) and excellent environmental adaptability. This study paves the way for the design and fabrication of high-performance multifunctional/flexible ICHs for wearable sensing, energy-storage, and energy-harvesting applications.

Positive correlation between lipid accumulation product index and arterial stiffness in Chinese patients with type 2 diabetes.

Background: Many studies have confirmed that lipid accumulation products (LAP) predict arterial stiffness (AS) in hypertensive patients. But there is little research on the use of LAP in identifying early atherosclerosis in patients with type 2 diabetes mellitus (T2DM). The aim of this study was to determine the relationship between the LAP index and brachial-ankle pulse wave velocity (baPWV) in Chinese patients with T2DM. Methods: A total of 1471 Chinese participants with T2DM, ranging in age from 18 to 80, were included in this cross-sectional study. BaPWV measurements were used to calculate the AS. A baPWV greater than the 75th percentile (1700 cm/s) was defined as indicating increased AS. The LAP index was calculated from the combination of waist circumference (WC) and triglycerides (TG). Results: According to the quartiles of the LAP index, baPWV tended to increase after adjusting for sex and age. Multiple linear regression analysis showed that the beta coefficient (ß) of baPWV increased by 31.0 cm/s for each unit of lnLAP that was increased, and the 95% confidence interval (CI) was (6.5, 55.5) cm/s. In multivariate logistic regression analyses, after fully adjusting for confounders, the risk of elevated baPWV increased with each unit increase in lnLAP, with an odds ratio (OR) of 1.3 (95% CI: 1.0, 1.8). According to the generalized additive model (GAM), we found that lnLAP was positively correlated with baPWV and baPWV elevation. The results were the same for males and females. Subgroup analyses showed that the positive correlation between lnLAP and elevated baPWV did not interact across all subgroups. Conclusions: In Chinese patients with T2DM, LAP was strongly and positively correlated with baPWV and elevated baPWV.

1,2,4-Triazole benzamide derivative TPB against Gaeumannomyces graminis var. tritici as a novel dual-target fungicide inhibiting ergosterol synthesis and adenine nucleotide transferase function.

BACKGROUND: Isopropyl 4-(2-chloro-6-(1H-1,2,4-triazol-1-yl)benzamido)benzoate (TPB) was a 1,2,4-triazole benzoyl arylamine derivative with excellent antifungal activity, especially against Gaeumannomyces graminis var. tritici (Ggt). Its mechanism of action was investigated by transmission electron microscopy (TEM) observation, assays of sterol composition, cell membrane permeability, intracellular ATP and mitochondrial membrane potential, and mPTP permeability, ROS measurement, RNA sequencing (RNA-seq) analysis. RESULTS: TPB interfered with ergosterol synthesis, reducing ergosterol content, increasing toxic intermediates, and finally causing biomembrane disruption such as increasing cell membrane permeability and content leakage, and destruction of organelle membranes such as coarse endoplasmic reticulum and vacuole. Moreover, TPB destroyed the function of adenine nucleotide transferase (ANT), leading to ATP transport obstruction in mitochondria, inhibiting mPTP opening, inducing intracellular ROS accumulation and mitochondrial membrane potential loss, finally resulting in mitochondrial damage including mitochondria swelled, mitochondrial membrane dissolved, and cristae destroyed and reduced. RNA-seq analyses showed that TPB increased the expression of ERG11, ERG24, ERG6, ERG5, ERG3 and ERG2 genes in ergosterol synthesis pathway, interfered with the expression of genes (NDUFS5, ATPeV0E, NCA2 and Pam17) related to mitochondrial structure, and inhibited the expression of genes (WrbA and GST) related to anti-oxidative stress. CONCLUSIONS: TPB exhibited excellent antifungal activity against Ggt by inhibiting ergosterol synthesis and destroying ANT function. So, TPB was a novel compound with dual-target mechanism of action and can be considered a promising novel fungicide for the control of wheat Take-all. The results provided new guides for the structural design of active compounds and powerful tools for pathogen resistance management. © 2023 Society of Chemical Industry.

Gamma-glutamyl transferase to high-density lipoprotein cholesterol ratio is a more powerful marker than TyG index for predicting metabolic syndrome in patients with type 2 diabetes mellitus.

Purpose: The prevalence of metabolic syndrome (MetS) is increasing globally and has become a global and national public health problem that cannot be ignored as an independent predictor of cardiovascular events, cancer and all-cause mortality. γ-glutamyl transferase (GGT) and high-density lipoprotein cholesterol (HDL-C) are associated with insulin resistance, dyslipidemia and oxidative stress. This study was designed to explore the relationship and predictive performance between γ-glutamyl transferase high-density lipoprotein cholesterol ratio (GGT/HDL-C) and MetS. Methods: This was a cross-sectional study. MetS was diagnosed from biochemical and anthropometric data in subjects with T2DM. Multivariate logistic regression was used to analyses the relationship between GGT/HDL-C ratio, TyG index and HOMA-IR and MetS in subjects with T2DM. Receiver operating characteristic (ROC) curve was drawn and the areas under the curve (AUC) were used to assess the ability of these indexes in screening MetS in subjects with T2DM. Statistical differences between the AUC values of these indexes were compared. In addition, we performed subgroup analyses and interactions. Results: 769 (70.55%) patients with T2DM were defined as having MetS. patients with MetS had higher anthropometric values and biochemical indicators compared to those without MetS. Multivariate logistic regression analysis of GGT/HDL-C ratio was an independent risk factor for MetS (Per 1 SD increase, OR = 2.49, 95% CI: 1.51, 4.10). According to ROC curve analysis, the value of GGT/HDL-C ratio in predicting MetS in subjects with T2DM was superior to that of TyG index and HOMA-IR. The best cut-off value for GGT/HDL-C prediction was 19.94. Conclusions: GGT/HDL-C ratio may be an important predictor of MetS in subjects with T2DM, and its predictive power is stronger than that of TyG index and HOMA-IR. The risk of MetS in subjects with T2DM is increased in the presence of a higher GGT/HDL-C ratio.

Lysosomal control of dendritic cell function.

Lysosomal compartments undergo extensive remodeling during dendritic cell (DC) activation to meet the dynamic functional requirements of DCs. Instead of being regarded as stationary and digestive organelles, recent studies have increasingly appreciated the versatile roles of lysosomes in regulating key aspects of DC biology. Lysosomes actively control DC motility by linking calcium efflux to the actomyosin contraction, while enhanced DC lysosomal membrane permeability contributes to the inflammasome activation. Besides, lysosomes provide a platform for the transduction of innate immune signaling and the intricate host-pathogen interplay. Lysosomes and lysosome-associated structures are also critically engaged in antigen presentation and cross-presentation processes, which are pivotal for the induction of antigen-specific adaptive immune response. Through the current review, we emphasize that lysosome targeting strategies serve as vital DC-based immunotherapies in fighting against tumor, infectious diseases, and autoinflammatory disorders.

Double-edged sword of technological progress to climate change depends on positioning in global value chains.

Technological progress (TP) is a double-edged sword to global climate change. This study for the first time reveals rebound and mitigation effects of efficiency-related TP in global value chains (GVCs) on greenhouse gas (GHG) emissions. The integrated effects of TP depend on the positioning of sectors in GVCs. The cost-saving TP in upstream sectors would stimulate downstream demand. This produces stronger rebound effects than mitigation potentials and leads to global GHG emission increments (e.g. TP in the gas sector of China and petroleum and coal products sector of South Korea). In contrast, sectors located in the trailing end of GVCs have greater potentials for GHG emission mitigation through TP, mainly due to the reduction of upstream inputs. (e.g. the construction sector of China and dwelling sector of the United States). Global GHG emissions and production outputs can be either a trade-off or a win-win relationship on account of TP than rebound effects, because TP in different sectors could possibly increase or decrease the emission intensity of GVCs. This study could recognize the most productive spots for GHG emission mitigation through efficiency-related TP. It provides a new perspective for international cooperation to promote global GHG emission mitigation.

The Use of Multidimensional Nomial Logistic Model and Structural Equation Model in the Validation of the 14-Item Health-Literacy Scale in Chinese Patients Living with Type 2 Diabetes.

Objective: To evaluate the psychometric properties of the 14-item health literacy scale (HL-14) in patients living with type 2 diabetes mellitus (T2DM) in clinical setting. Methods: Cross-sectional study using item response theory and structural equation modeling (SEM) for testing the item difficulty and three dimensional-HL configurations was adopted in this study. Chinese patients living with T2DM admitted to endocrinology department of Huadong hospital were evaluated by the HL-14 including communication, functional and critical health literacy from August to December 2021. Results: The multidimensional random coefficients multinomial logistic model indicated the difficulty settings of the scale are appropriate for the study populations, and differential item functioning was not observed for sex in the study. SEM demonstrated that the three-dimensional configuration of the scale is good in the study population (x2/df=2.698, Comparative Fit Index = 0.965, Root Mean Square Error of Approximation = 0.076, standard residual mean root = 0.042). Conclusion: The HL-14 scale is a reliable and valid measurement, which can perform equitably across sex in evaluating the health literacy in Chinese patients living with T2DM. Moreover, the scale may help fill the gaps of multidimensional health literacy assessment and rapid screening of health literacy ability for clinical practice.

Cancer-cell-secreted miR-204-5p induces leptin signalling pathway in white adipose tissue to promote cancer-associated cachexia.

Cancer-associated cachexia is a multi-organ weight loss syndrome, especially with a wasting disorder of adipose tissue and skeletal muscle. Small extracellular vesicles (sEVs) serve as emerging messengers to connect primary tumour and metabolic organs to exert systemic regulation. However, whether and how tumour-derived sEVs regulate white adipose tissue (WAT) browning and fat loss is poorly defined. Here, we report breast cancer cell-secreted exosomal miR-204-5p induces hypoxia-inducible factor 1A (HIF1A) in WAT by targeting von Hippel-Lindau (VHL) gene. Elevated HIF1A protein induces the leptin signalling pathway and thereby enhances lipolysis in WAT. Additionally, exogenous VHL expression blocks the effect of exosomal miR-204-5p on WAT browning. Reduced plasma phosphatidyl ethanolamine level is detected in mice lack of cancer-derived miR-204-5p secretion in vivo. Collectively, our study reveals circulating miR-204-5p induces hypoxia-mediated leptin signalling pathway to promote lipolysis and WAT browning, shedding light on both preventive screenings and early intervention for cancer-associated cachexia.

Quercetin serves as the major component of Xiang-lian Pill to ameliorate ulcerative colitis via tipping the balance of STAT1/PPARγ and dictating the alternative activation of macrophage.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese herbal formula, Xiang-lian Pill (XLP), is commonly prescribed for ulcerative colitis (UC) patients to relieve their clinical symptom. Nonetheless, the underlying cellular and molecular mechanisms of XLP's anti-UC effect remain incompletely understood. AIM OF THE STUDY: To evaluate the therapeutic effect and elucidate the possible working mechanisms of XLP in UC treatment. The major active component of XLP was also characterized. MATERIALS AND METHODS: Colitis was induced in C57BL/6 mice with 3% dextran sulfate sodium (DSS) dissolved in drinking water for 7 consecutive days. The UC mice were grouped and treated with XLP (3640 mg/kg) or vehicle orally during the procedure of DSS induction. Mouse body weight, disease activity index (DAI) score and colon length were recorded. Histopathological changes and inflammatory cell infiltration were evaluated by pathological staining and flow cytometric analysis (FACS). Network pharmacology, bioinformatic analysis, widely targeted and targeted metabolomics analysis were performed to screen the potential effective ingredients and key targets. Bone marrow derived macrophages (BMDMs), peripheral blood mononuclear cells (PBMCs), RAW264.7 and THP-1 cells were used to dissect the anti-inflammatory effect of XLP. RESULTS: Oral administration of XLP ameliorated DSS induced mouse colitis, as evidenced by reduced DAI and colonic inflammatory destruction. FACS results demonstrated that XLP treatment effectively restored immune tolerance in colon, inhibited the generation of monocyte derived macrophages and skewed macrophage polarization into M2 phenotype. Network pharmacology analysis suggested that innate effector modules related to macrophage activation comprise the major targets of XLP, and the counter-regulatory STAT1/PPARγ signaling possibly serves as the critical downstream pathway. Subsequent experiments unveiled an imbalance of STAT1/PPARγ signaling in monocytes derived from UC patients, and validated that XLP suppressed LPS/IFN-γ induced macrophage activation (STAT1 mediated) but facilitated IL-4 induced macrophage M2 polarization (PPARγ dependent). Meanwhile, our data showed that quercetin served as the major component of XLP to recapitulate the regulatory effect on macrophages. CONCLUSION: Our findings revealed that quercetin serves as the major component of XLP that regulates macrophage alternative activation via tipping the balance of STAT1/PPARγ, which provides a mechanistic explanation for the therapeutic effect of XLP in UC treatment.

Consumption in Non-Pastoral Regions Drove Three-Quarters of Forage-Livestock Conflicts in China.

Forage-livestock conflict (FLC) is a major anthropogenic cause of rangeland degradation. It poses tremendous threats to the environment owing to its adverse impacts on carbon sequestration, water supply and regulation, and biodiversity conservation. Existing policy interventions focus on the in situ FLCs induced by local production activities but overlook the role of consumption activities in driving FLCs. Here, we investigate the spatiotemporal variations in China's FLCs and the domestic final consumers at the county level by combining remote sensing data and multi-regional input-output model. Results show that during 2005-2015, China's pastoralism induced an average of 82 million tons of FLCs per year. Domestic final demand was responsible for 85-93% of the FLCs in China. There was spatiotemporal heterogeneity in domestic consumption driving China's FLCs. In particular, the final demand of non-pastoral regions was responsible for around three-quarters (74-79%) of the total FLCs throughout the decade. The rangeland-based livestock raising, agricultural and sideline product processing, and catering sectors are important demand-side drivers. These findings can support targeted demand-side strategies and interregional cooperation to reduce China's FLCs, thus mitigating rangeland degradation.

Comparative analysis of pre- and postmenopausal endometrial cancer in 216 patients.

Background: Endometrial carcinoma (EC) is one of the most common gynecological malignancies and has become more prevalent in recent decades. The clinical manifestations and characteristics of EC in premenopausal and postmenopausal women differ and present with distinct pathological stages and subtypes of EC. Surgery remains the principal therapeutic approach, but the postoperative prognosis is largely affected by the pathological state. Methods: A retrospective study was conducted on 216 patients with EC who were hospitalized from August 2008 to August 2019 in Wuhan Union Hospital. The patients were divided into 2 groups based on the pre- or postmenopausal occurrence of EC. The general clinical characteristics, intraoperative situation, clinicopathological data, and postoperative outcomes of the 2 groups were compared. Results: Patients with premenopausal EC had earlier menarche, a higher incidence of primary infertility and anemia, and fewer pregnancies and deliveries. Patients with postmenopausal EC were older and often had hyperlipidemia and diabetes. Additionally, patients who were postmenopausal had worse tumor pathological gradings, more severe muscular invasion, and a higher rate of lymphatic metastasis. These factors led to a higher demand for postoperative radiotherapy in patients but a lower survival rate. Conclusions: Generally, premenopausal EC differs from postmenopausal EC: the latter is more malignant and has a worse prognosis.

Potential Regulation for Surface-Enhanced Raman Scattering Detection and Identification of Carotenoids.

Surface-enhanced Raman scattering (SERS) is often impaired by the limited affinity of molecules to plasmonic substrates. Here, we use carbon fiber microelectrodes modified with silver nanoparticles as a plasmonic microsubstrate with tunable affinity for enrichment and molecular identification by SERS. The silver nanoparticles self-assemble by electrostatic interaction with diamine molecules that are electrochemically grafted onto the surface of the microelectrodes. ß-carotene and trans-ß-Apo-8'-carotenal, producing similar resonant SERS spectra, are employed as model molecules to study the effect of electroenrichment and SERS screening for different electrode potentials. The data show that at a characteristic electrode potential, the low affinity of polyene chains without hydrophilic groups to the substrate can be overcome. Different potentials were applied to recognize the two types of carotenoids by their typical SERS signal, and the applicability of this strategy was further confirmed in the environment of a real cell culture. The results indicate that by regulating the potential, carotenoid molecules with a similar molecular structure can be selectively quantified and identified by SERS. The developed SERS-active microelectrode is expected to help the development of portable, miniaturized point-of-care diagnostic SERS sensors.

Optimal Anthropometric Indicators and Cut Points for Predicting Metabolic Syndrome in Chinese Patients with Type 2 Diabetes Mellitus by Gender.

Purpose: The best predictors and cut points for metabolic syndrome (MetS) in Chinese patients with type 2 diabetes (T2DM) were determined by comparing six anthropometric measures: body mass index (BMI), triglyceride-glucose (TyG), the product of TyG and waist-to-hip ratio (TyG-WHpR), the product of TyG and waist-to-height ratio (TyG-WHtR), the product of TyG and waist circumference (TyG-WC), and the product of TyG and body mass index (TyG-BMI). Patients and Methods: Sixteen hundred and sixty-five adult patients with T2DM were collected, and the ability and cut points of each index to predict MetS were compared by plotting the receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC) values. Then, logistic regression analysis was used to adjust for confounders, including adjustment for menopause in women, to obtain the odds ratio (OR) and 95% confidence interval (CI). Results: MetS was present in 71.60% of T2DM patients, 75.00% of men, and 67.02% of women. BMI was the best predictor of MetS in men with T2DM (AUC = 0.8646, 95% CI: 0.8379-0.8912), with a cut point of 24.5500 kg/m2 (specificity: 0.7714; sensitivity: 0.7533), and TyG-WC was the best predictor of MetS in women with T2DM (AUC = 0.8362, 95% CI: 0.8034-0.8690), with a cut point of 154.1548 (specificity: 0.7455; sensitivity: 0.8076). Conclusion: The best predictor of MetS in adults with T2DM is BMI with a cut point of 24.5500 kg/m2 for men and TyG-WC with a cut point of 154.1548 for women.

UBC9 deficiency enhances immunostimulatory macrophage activation and subsequent antitumor T cell response in prostate cancer.

The role of tumor-associated macrophages (TAMs), along with the regulatory mechanisms underlying distinct macrophage activation states, remains poorly understood in prostate cancer (PCa). Herein, we report that PCa growth in mice with macrophage-specific Ubc9 deficiency is substantially suppressed compared with that in wild-type littermates, an effect partially ascribed to the augmented CD8+ T cell response. Biochemical and molecular analyses revealed that signal transducer and activator of transcription 4 (STAT4) is a crucial UBC9-mediated SUMOylation target, with lysine residue 350 (K350) as the major modification site. Site-directed mutation of STAT4 (K350R) enhanced its nuclear translocation and stability, thereby facilitating the proinflammatory activation of macrophages. Importantly, administration of the UBC9 inhibitor 2-D08 promoted the antitumor effect of TAMs and increased the expression of PD-1 on CD8+ T cells, supporting a synergistic antitumor efficacy once it combined with the immune checkpoint blockade therapy. Together, our results demonstrate that ablation of UBC9 could reverse the immunosuppressive phenotype of TAMs by promoting STAT4-mediated macrophage activation and macrophage-CD8+ T cell crosstalk, which provides valuable insights to halt the pathogenic process of tumorigenesis.

Survival prediction for patients with malignant biliary obstruction caused by pancreatic cancer undergoing biliary drainage: the COMBO-PaS model.

BACKGROUND: Patients with pancreatic cancer-caused biliary obstruction (PC-BO) have poor prognosis, but we lack of tools to predict survival for clinical decision-making. This study aims to establish a model for survival prediction among patients with PC-BO. METHODS: A total of 172 patients with PC-BO treated with percutaneous biliary drainage were randomly divided into a training group (n = 120) and a validation group (n = 52). The independent risk factors for overall survival were selected to develop a Cox model. The predictive performance of M stage, hepatic metastases, cancer antigen 199, and the Cox model was determined. Naples prognostic score (NPS), the prognostic nutritional index (PNI), and the controlling nutritional status (CONUT) for 1-month mortality risk were compared with the Cox model. RESULTS: The Cox model was developed based on total cholesterol, direct bilirubin, hepatic metastases, cancer antigen 199, stenosis type, and preprocedural infection (all P < 0.05), which named "COMBO-PaS." The COMBO-PaS model had the highest area under the curves (AUC) (0.801-0.933) comparing with other predictors (0.506-0.740) for 1-, 3-, and 6-month survival prediction. For 1-month mortality risk prediction, the COMBO-PaS model had the highest AUC of 0.829 comparing with NPS, PNI, and CONUT. CONCLUSION: The COMBO-PaS model was useful for survival prediction among patients with PC-BO.

Amine-functionalized magnetic microspheres from lignosulfonate for industrial wastewater purification.

Amine-functionalized magnetic microspheres (LS-Fe-NMA) were successfully prepared from lignosulfonate by magnetization and amine modification to remove Cr(VI) from industrial wastewater. In addition to SEM, FTIR, XPS, magnetic hysteresis curves and other characterizations, the adsorption tests were performed in real Cr(VI)-containing industrial wastewater. The experimental influencing factors, such as adsorbent types, LS content in the composites, adsorption time, dosages of adsorbent and adsorption temperature were systematically explored. The results of adsorption models fitting proved that the adsorption conformed to the Langmuir model and the pseudo-second-order kinetic model. At 45 °C, the calculated equilibrium adsorption amount by LS-Fe-NMA in industrial wastewater was 642.11 mg/g. In addition, the adsorption process followed the principle of spontaneous endothermic reaction. It was found that electrostatic interaction, redox and complexation existed during the adsorption process. The excellent adsorption performance and reusability of LS-Fe-NMA for Cr(VI) demonstrates its practical application value in real Cr(VI)-containing industrial wastewater.

Arginine metabolism regulates the pathogenesis of inflammatory bowel disease.

The pathogenesis of inflammatory bowel disease (IBD) is related to genetic susceptibility, enteric dysbiosis, and uncontrolled, chronic inflammatory responses that lead to colonic tissue damage and impaired intestinal absorption. As a consequence, patients with IBD are prone to nutrition deficits after each episode of disease resurgence. Nutritional supplementation, especially for protein components, is often implemented during the remission phase of IBD. Notably, ingested nutrients could affect the progression of IBD and the prognostic outcome of patients; therefore, they should be cautiously evaluated prior to being used for IBD intervention. Arginine (Arg) is a semi-essential amino acid required for protein synthesis and intimately associated with gut pathophysiology. To help optimize arginine-based nutritional intervention strategies, the present work summarizes that during the process of IBD, patients manifest colonic Arg deficiency and the turbulence of Arg metabolic pathways. The roles of Arg-nitric oxide (catalyzed by inducible nitric oxide synthase) and Arg-urea (catalyzed by arginases) pathways in IBD are debatable; the Arg-polyamine and Arg-creatine pathways are mainly protective. Overall, supplementation with Arg is a promising therapeutic strategy for IBD; however, the dosage of Arg may need to be carefully tailored for different individuals at different disease stages. Additionally, the combination of Arg supplementation with inhibitors of Arg metabolic pathways as well as other treatment options is worthy of further exploration.