Triptolide Inhibits Th17 Response by Upregulating microRNA-204-5p and Suppressing STAT3 Phosphorylation in Psoriasis.

Background: Psoriasis is an immune and inflammation-related skin disease. Triptolide with immunosuppressive and anti-inflammatory properties has been utilized for psoriasis treatment. However, the potential immunological mechanisms of triptolide have not been fully elucidated. Methods: Using an imiquimod (IMQ)-induced psoriatic mouse model, we detected the effects of triptolide on psoriasis-like lesions including scales, thickening, and erythema. Methyl thiazol tetrazolium (MTT) cytotoxicity assay was performed for evaluating the influence of triptolide on cell viability. Gene expression at mRNA and protein levels were examined by reverse transcription-quantitative polymerase chain reaction and Western blot analysis, respectively. The combination between microRNA-204-5p (miR-204-5p) and signal transduction and transcription activator-3 (STAT3) was confirmed by luciferase reporter assay. Enzyme-linked immunosorbent assay was conducted to examine interleukin (IL)-17 and interferon-γ (IFN-γ) levels using corresponding kits. Hematoxylin and eosin staining was used for the visualization of epidermal thickness. Flow cytometry analysis was employed for examining T helper (Th) 17 cells. Results: Triptolide ameliorated IMQ-induced psoriatic skin lesions manifested by the decreased psoriasis area and severity indexes (PASI) scores. Triptolide inhibited Th17 cell differentiation from splenocytes. Additionally, triptolide elevated miR-204-5p expression, whereas it downregulated STAT3 expression levels both in vitro and in vivo. Moreover, miR-204-5p directly targeted STAT3 in HaCaT cells. Furthermore, triptolide repressed the expression of proinflammatory cytokines in IMQ-evoked psoriasis-like mice. Conclusion: Triptolide inhibits STAT3 phosphorylation via upregulating miR-204-5p and thus suppressing Th17 response in psoriasis.

Understanding physical exercise among individuals with substance use disorders using an integrated theoretical perspective of the health action process approach and theory of planned behavior.

Introduction: Physical exercise is considered a useful non-pharmacological adjunctive treatment for promoting recovery from substance use disorders (SUD). However, adherence to physical exercise treatments is low, and little is known about what factors are associated with the initiation and maintenance of physical exercise behaviors. The aim of this study was to explore the psychosocial factors underlying these behaviors in individuals with SUD using an integrated theoretical model based on the health action process approach (HAPA) and the theory of planned behavior (TPB). Methods: A total of 1,197 individuals with SUDs (aged 37.20 ± 8.62 years) were recruited from 10 compulsory isolation drug rehabilitation centers in Zhejiang Province via convenience sampling according to a set of inclusion criteria. Self-reported data were collected to assess task self-efficacy (TSE), maintenance self-efficacy (MSE), recovery self-efficacy (RSE), outcome expectations (OE), action planning (AP), coping planning (CP), social support (SS), subjective norms (SN), attitude behavior (AB), behavioral intention (BI), perceived behavioral control (PBC), risk perception (RP), exercise stage, and exercise behavior in this integrated model. ANOVA and structural equation modeling (SEM) were used to evaluate this model. Results: One-way ANOVA revealed that the majority of the moderating variables were significantly different in the exercise phase. Further SEM showed that the model fit the data and revealed several important relationships. TSE, RP, SS, AB, and SN were indirectly associated with physical exercise behavior in individuals with SUD through the BI in the SUD initiation stage. In addition, PBC was directly related to physical exercise behavior in individuals with SUD. In the maintenance stage, MSE, AP, CP and exercise behavior were significantly related. Moreover, AP and CP were mediators of BI and MSE. Conclusion: This study is the first attempt to integrate patterns of physical exercise behavior in individuals with SUD. The HAPA-TPB integration model provides a useful framework for identifying determinants of physical exercise behavioral intentions and behaviors in individuals with SUD and for explaining and predicting the initiation and maintenance of physical exercise behaviors in these individuals. Moreover, the model provides scientific guidance for the enhancement of physical exercise adherence in individuals with SUD.

Chronic Heat Stress Induces Oxidative Stress and Induces Inflammatory Injury in Broiler Spleen via TLRs/MyD88/NF-κB Signaling Pathway in Broilers.

The spleen is the largest peripheral immune organ of the organism, accounting for 25% of the total lymphoid tissue of the body. During HS, the spleen is damaged due to the elevated environment, which seriously affects life performance and broilers' health. This study aimed to investigate the mechanism of chronic HS damage to broiler spleen tissues. The broilers were typically raised until they reached 21 days of age, after which they were arbitrarily allocated into two groups: an HS group and a cntrol group. The HS group was subjected to a temperature of 35 °C for 10 h each day, starting at 21 days of age. At 35 and 42 days of age, spleen and serum samples were obtained from the broilers. The results showed that after HS, a significant decrease in productive performance was observed at 42 days of age (p < 0.01), and the spleen index, and bursa index were significantly decreased (p < 0.01). T-AOC of the organism was significantly decreased (p < 0.05), GSH-PX, SOD, and CAT antioxidant factors were significantly decreased (p < 0.01), and MDA was significantly elevated (p < 0.01). HS also led to a significant increase in cytokines IL-6, TNF-α, and INF-γ and a significant decrease in IL-4 in the spleen. The histopathologic results showed that the spleen's red-white medulla was poorly demarcated. The cells were sparsely arranged after HS. After HS, the expression of TLRs, MYD88, and NF-κB genes increased significantly. The expression of HSP70 increased significantly, suggesting that HS may induces an inflammatory response in broiler spleens through this signaling pathway, which may cause pathological damage to broiler spleens, leading to a decrease in immune function and progressively aggravating HS-induced damage with the prolongation of HS.

Research progress of electrode shapes in EWOD-based digital microfluidics.

Digital microfluidics (DMF) is an innovative technology used for precise manipulation of liquid droplets. This technology has garnered significant attention in both industrial applications and scientific research due to its unique advantages. Among the key components of DMF, the driving electrode plays a role in facilitating droplet generation, transportation, splitting, merging, and mixing. This comprehensive review aims to present an in-depth understanding of the working principle of DMF particularly focusing on the Electrowetting On Dielectric (EWOD) method. Furthermore, it examines the impact of driving electrodes with varying geometries on droplet manipulation. By analyzing and comparing their characteristics, this review offers valuable insights and a fresh perspective on the design and application of driving electrodes in DMF based on the EWOD approach. Lastly, an assessment of the development trend and potential applications of DMF concludes the review, providing an outlook for future prospects in the field.

Priority control sequence of 34 typical pollutants in effluents of Chinese wastewater treatment plants.

The identification of the priority control sequence of pollutants in effluents of wastewater treatment plants (WWTPs) has important implications for the management of water quality. This study chose 34 typical pollutants based on their representativeness and detection rates in municipal wastewater. The occurrence frequency and concentration of these pollutants in 168 Chinese WWTP effluents were measured at the national level. The data on in vitro toxicity (67 assays) and in vivo toxicity (216 species) for target pollutants were obtained from the public toxicity database and our experimental data. An environmental health prioritization index (EHPi) method was proposed to integrate the occurrence frequency, concentration, removal rate, and in vitro and in vivo toxicity to determine the priority control sequence of target pollutants. Ethynyl estradiol, 17ß-estradiol, estrone, diclofenac, and atrazine were the top 5 pollutants identified by the EHPi score. Several pollutants with high EHPi scores showed spatial differences. Besides the EHPi method which was from the single pollutant perspective, the combined toxicity of pollutants (300 pairs of binary combinations) was also measured based on in vitro toxicity assays to evaluate the key pollutants from the pollutant-pollutant interacting perspective. The pollutants (such as ofloxacin and acetaminophen) that could have significant synergetic effects with many other pollutants are worthy of prior attention. This study shed new light on the identification of the priority control sequence of pollutants in WWTP effluents. The results provide meaningful data for the effective management and control of wastewater water quality.

Chronic heat stress induces lung injury in broiler chickens by disrupting the pulmonary blood-air barrier and activating TLRs/NF-κB signaling pathway.

As an important respiratory organ, the lung is susceptible to damage during heat stress due to the accelerated breathing frequency caused by an increase in environmental temperature. This can affect the growth performance of animals and endanger their health. This study aimed to explore the mechanism of lung tissue damage caused by heat stress. Broilers were randomly divided into a control group (Control) and a heat stress group (HS). The HS group was exposed to 35°C heat stress for 12 h per d from 21-days old, and samples were taken from selected broilers at 28, 35, and 42-days old. The results showed a significant increase in lactate dehydrogenase (LDH) activity in the serum and myeloperoxidase (MPO) activity in the lungs of broiler chickens across all 3 age groups after heat stress (P < 0.01), while the total antioxidant capacity (T-AOC) was significantly enhanced at 35-days old (P < 0.01). Heat stress also led to significant increases in various proinflammatory factors in serum and expression levels of HSP60 and HSP70 in lung tissue. Histopathological results showed congestion and bleeding in lung blood vessels, shedding of pulmonary epithelial cells, and a large amount of inflammatory infiltration in the lungs after heat stress. The mRNA expression of TLRs/NF-κB-related genes showed an upward trend (P < 0.05) after heat stress, while the mRNA expression of MLCK, a gene related to pulmonary blood-air barrier, significantly increased after heat stress, and the expression levels of MLC, ZO-1, and occludin decreased in contrast. This change was also confirmed by Western blotting, indicating that the pulmonary blood-air barrier is damaged after heat stress. Heat stress can cause damage to the lung tissue of broiler chickens by disrupting the integrity of the blood-air barrier and increasing permeability. This effect is further augmented by the activation of TLRs/NF-κB signaling pathways leading to an intensified inflammatory response. As heat stress duration progresses, broiler chickens develop thermotolerance, which gradually mitigates the damaging effects induced by heat stress.

Fabrication of CoSe2/CoP with rich selenium- and phosphorus-vacancies and heterogeneous interfaces for asymmetric supercapacitors.

CoSe2/CoP with rich Se- and P-vacancies and heterogeneous interfaces (v-CoSe2/CoP) is grown on the surface of nickel foam via a two-step strategy: electrodeposition and NaBH4 reduction, which can be used as the cathode material in asymmetric supercapacitors. The SEM characterization reveals the honeycomb-like structure of the v-CoSe2/CoP, and the results of EPR, XPS and HRTEM reveal the existence of anionic vacancies and heterogeneous interfaces in the v-CoSe2/CoP. The as-fabricated v-CoSe2/CoP exhibits high specific capacitance (3206 mF cm-2 at 1.0 mA cm-2) and cyclic stability (91 % capacitance retention after 2000 cycles). An asymmetric supercapacitor is assembled by using the v-CoSe2/CoP and activated carbon (AC) as cathode and anode materials, respectively, which displays a high energy density of 40.6 Wh kg-1 at the power density of 211.5 W kg-1. The outstanding electrochemical performances of the v-CoSe2/CoP might be ascribed to the synergistic effects of Se- and P-vacancies and the heterogeneous interfaces in the v-CoSe2/CoP.

Reduced Mo-doped NiCo2O4 with rich oxygen vacancies as an advanced electrode material in supercapacitors.

Reduced Mo-doped NiCo2O4 (R-Mo-NiCo2O4) was facilely prepared through a dual-defect strategy. Mo-doped NiCo layered double hydroxide (Mo-NiCo-LDH) was used as the precursor and calcined in an air atmosphere, and the resultant Mo-doped NiCo2O4 (Mo-NiCo2O4) was further reduced by NaBH4. The number of oxygen vacancies in the obtained R-Mo-NiCo2O4 is significantly increased by both Mo doping and NaBH4 reduction, resulting in greatly enhanced electrical conductivity and facilitated charge transfer. Finally, the R-Mo-NiCo2O4 was used as the electrode material in supercapacitors, which displayed greatly improved electrochemical performance, such as higher specific capacity (285.8 mA h g-1 at 1 A g-1), rate capability (86.1%) and cycling stability (87.4% retention after 5000 cycles).

Fabrication and characterization of ZnO nanofilms using extracted pectin of Premna microphylla Turcz leaves and carboxymethyl cellulose.

The current study sought to fabricate pectin nano-films from Premna microphylla Turcz (PMTP) leaves using a combination of ZnO-carboxymethyl cellulose. The rheological and physical properties of fabricated nano-ZnO films were studied. Spectroscopy FT-IR, microscopic study (SEM), thermogravimetry (TG), and XRD were applied to characterize the fabricated film. The antibacterial activity of the nanofilm was determined using the antibacterial circle method. The findings showed that the addition of PMTP can reduce the nanofilm color, water solubility/hydrophilicity, air permeability, and ultraviolet light permeability of the nanofilm. Treatment CPN0.5 achieved the optimized Tensile strength (TS) of 4.50 Mpa, significant differences compared to CPN2 (3.99 Mpa) and CPN1 (3.65 Mpa). In addition, treatment CPN1 achieved the lowest WVP value (29.35) compared to the highest value (41.62) achieved by CPN0.5 treatment with no significant differences with CPN3 (29.7) and CPN1 (30.98) treatments. Elongation (E%) at break was the best for each CP10 (74.9) and CPN0.5 (73.03). Moreover, ZnO can enhance the nanofilm activity and the nanofilm water swelling ratio. Furthermore, adding ZnO to the nano-formula improved the antibacterial activity of the fabricated film against Staphylococcus aureus. In sum, nanofilms fabricated of PMTP and ZnO possess promising prospects as antibacterial agents in packaging applications.

Gpr174 Knockout Alleviates DSS-Induced Colitis via Regulating the Immune Function of Dendritic Cells.

Background: Dysfunction of the immune system would disturb the intestinal homeostasis and lead to inflammatory bowel disease (IBD). Dendritic cells (DCs) help maintain intestinal homeostasis and immediately respond to pathogens or injuries once the mucosa barriers are destroyed during IBD. G protein-coupled receptors(GPR)174 is an essential regulator of immunity that is widely expressed in most immune cells, including DCs. However, the role of GPR174 in regulating the immune function of DC in colitis has not been investigated. Methods: Dextran sodium sulfate (DSS) was administered to establish the mice colitis model. Data of weight, length of colon, disease activity index (DAI), and macroscopic scores were collected. The flow cytometry was used to detect the infiltrations of T cells and DCs, the mean fluorescence intensity (MFI) of CD80, CD86, CD40, and major histocompatibility complex-II (MHC-II). And T cells proliferataion was measured by carboxyfluorescein diacetate succinimidyl ester (CFSE). The expression of cytokines (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), interferon-γ (IFN-γ), interleukin -4 (IL-4)) and GPR174 mRNA were measured by Elisa, quantitative polymerase chain reaction (qPCR), and immunofluorescence. RNA of bone-marrow-derived dendritic cells (BMDCs) was extracted for sequencing. Adoptive transfer of BMDCs was administrated intravenously. Results: Gpr174-/- mice exposed to 3% DSS showed significant alleviation characterized by reduced loss of weight, more minor colon damage, and better DAI and macroscopic scores. The expression of pro-inflammatory cytokines (TNF-α, IL-6) decreased, while anti-inflammatory cytokine (IL-10) increased compared with WT mice. In vitro, Gpr174-/- BMDCs showed less maturity, with a declined expression of MHC-II, CD80, CD86 and reduced TNF-α, higher IL-10 after LPS stimulation. Gpr174-/- BMDCs were less capable of activating OT-II naïve CD4+ T cells than WT BMDCs and induced more Th0 cells to differentiate into Treg while less into Th1. Furthermore, the transcriptome sequencing analysis exhibited that Gpr174 participated in TNF-α (NF-κB) signaling, leukocyte transendothelial migration, and Th1/Th2 cell differentiation pathways. Adoptive transfer of Gpr174-/- BMDCs to WT mice ameliorated DSS-induced colitis. Conclusion: Our study indicated that GPR174 was involved in the pathogenesis of IBD by regulating the maturation of the dendritic cells to maintain immune homeostasis. TNF-α (NF-κB) signaling pathway, leukocyte transendothelial migration, and Th1/Th2 cell differentiation pathways may be the target pathway.

Artificial intelligence computed tomography helps evaluate the severity of COVID-19 patients: A retrospective study.

BACKGROUND: Computed tomography (CT) is a noninvasive imaging approach to assist the early diagnosis of pneumonia. However, coronavirus disease 2019 (COVID-19) shares similar imaging features with other types of pneumonia, which makes differential diagnosis problematic. Artificial intelligence (AI) has been proven successful in the medical imaging field, which has helped disease identification. However, whether AI can be used to identify the severity of COVID-19 is still underdetermined. METHODS: Data were extracted from 140 patients with confirmed COVID-19. The severity of COVID-19 patients (severe vs. non-severe) was defined at admission, according to American Thoracic Society (ATS) guidelines for community-acquired pneumonia (CAP). The AI-CT rating system constructed by Hangzhou YITU Healthcare Technology Co., Ltd. was used as the analysis tool to analyze chest CT images. RESULTS: A total of 117 diagnosed cases were enrolled, with 40 severe cases and 77 non-severe cases. Severe patients had more dyspnea symptoms on admission (12 vs. 3), higher acute physiology and chronic health evaluation (APACHE) II (9 vs. 4) and sequential organ failure assessment (SOFA) (3 vs. 1) scores, as well as higher CT semiquantitative rating scores (4 vs. 1) and AI-CT rating scores than non-severe patients (P<0.001). The AI-CT score was more predictive of the severity of COVID-19 (AUC=0.929), and ground-glass opacity (GGO) was more predictive of further intubation and mechanical ventilation (AUC=0.836). Furthermore, the CT semiquantitative score was linearly associated with the AI-CT rating system (Adj R 2=75.5%, P<0.001). CONCLUSIONS: AI technology could be used to evaluate disease severity in COVID-19 patients. Although it could not be considered an independent factor, there was no doubt that GGOs displayed more predictive value for further mechanical ventilation.

Predictive Significance of the Prognostic Nutritional Index (PNI) in Patients with Severe COVID-19.

BACKGROUND: The prognostic nutritional index (PNI) has been reported to significantly correlate with poor survival and postoperative complications in patients with various diseases, but its relationship with mortality in COVID-19 patients has not been addressed. METHOD: A multicenter retrospective study involving patients with severe COVID-19 was conducted to investigate whether malnutrition and other clinical characteristics could be used to stratify the patients based on risk. RESULTS: A total of 395 patients were included in our study, with 236 patients in the training cohort, 59 patients in the internal validation cohort, and 100 patients in the external validation cohort. During hospitalization, 63/236 (26.69%) and 14/59 (23.73%) patients died in the training and validation cohorts, respectively. PNI had the strongest relationships with the neutrophil-lymphocyte ratio (NLR) and lactate dehydrogenase (LDH) level but was less strongly correlated with the CURB65, APACHE II, and SOFA scores. The baseline PNI score, platelet (PLT) count, LDH level, and PaO2/FiO2 (P/F) ratio were independent predictors of mortality in COVID-19 patients. A nomogram incorporating these four predictors showed good calibration and discrimination in the derivation and validation cohorts. A PNI score less than 33.405 was associated with a higher risk of mortality in severe COVID-19 patients in the Cox regression analysis. CONCLUSION: These findings have implications for predicting the risk of mortality in COVID-19 patients at the time of admission and provide the first direct evidence that a lower PNI is related to a worse prognosis in severe COVID-19 patients.

Multiplex immunoassays reveal increased serum cytokines and chemokines associated with the subtypes of achalasia.

BACKGROUND: Achalasia is an esophageal motility disorder with unknown etiology. Previous findings indicate that immune-mediated inflammatory process causes inhibitory neuronal degeneration. This study was designed to evaluate levels of serological cytokines and chemokines in patients with achalasia. METHODS: We collected information from forty-seven patients with achalasia who underwent peroral endoscopic myotomy. Control samples were collected from forty-seven age- and sex-matched healthy people. The concentrations of serological cytokines and chemokines were analyzed by Luminex xMAP immunoassay. Serological and clinical data were compared between groups. KEY RESULTS: Compared with healthy controls, achalasia patients had significantly increased concentrations of eleven cytokines and chemokines, namely, TGF-ß1 (P < .001), TGF-ß2 (P < .001), TGF-ß3 (P < .001), IL-1ra (P < .001), IL-17 (P = .005), IL-18 (P < .001), IFN-γ (P < .001), MIG (P < .001), PDGF-BB (P < .001), IP-10 (P = .003), and SCGF-B (P < .001). Gene ontology (GO) and network functional enrichment analysis revealed regulation of signaling receptor activity and receptor-ligand activity were the most related pathways of these cytokines and chemokines. Levels of twelve cytokines and chemokines were significantly increased in type III compared with I/II achalasia, namely, TGF-ß2, IL-1ra, IL-2Ra, IL-18, MIG, IFN-γ, SDF-1a, Eotaxin, PDGF-BB, IP-10, MCP-1, and TRAIL. CONCLUSIONS AND INFERENCES: Patients with achalasia exhibited increased levels of serological cytokines and chemokines. Levels of cytokines and chemokines were significantly increased in type III than in type I/II achalasia. Cytokines and chemokines might contribute to the inflammatory development of achalasia.