Isosilybin A exhibits anti-inflammatory properties in rosacea by inhibiting MAPK pathway and M1 macrophage polarization.

Rosacea is a chronic inflammatory skin disease, which is prone to flares and requires continuous management and treatment. However, long-term use of drugs can lead to additional adverse drug reactions. Based on the comorbid relationship between rosacea and Parkinson's disease, bioinformatics and network pharmacology analysis were used to identify a safer drug for rosacea. It has been demonstrated that ISA has an ameliorative impact on the symptoms of Parkinson's disease. The results demonstrated that ISA exhibited anti-inflammatory properties, including reducing erythema areas and inflammatory cell infiltration in rosacea-like mice models, and inhibiting the expression of inflammatory factors in cellular inflammation models. Furthermore, the anti-inflammatory effect of ISA was associated with inhibition of the Erk, p38 and NF-κB signaling pathways and inhibition of macrophage polarization to M1 type. In addition, molecular docking and drug affinity responsive target stability experiment results indicated that VEGFA and RELA were the direct targets of ISA in the treatment for rosacea. In conclusion, these results suggested that ISA may be a potential therapeutic agent for rosacea.

Therapeutic effects of Lingguizhugan decoction in a rat model of high-fat diet-induced insulin resistance.

BACKGROUND: Lingguizhugan (LGZG) decoction is a widely used classic Chinese medicine formula that was recently shown to improve high-fat diet (HFD)-induced insulin resistance (IR) in animal studies. AIM: To assess the therapeutic effect of LGZG decoction on HFD-induced IR and explore the potential underlying mechanism. METHODS: To establish an IR rat model, a 12-wk HFD was administered, followed by a 4-wk treatment with LGZG. The determination of IR status was achieved through the use of biochemical tests and oral glucose tolerance tests. Using a targeted meta-bolomics platform to analyze changes in serum metabolites, quantitative real-time PCR (qRT-PCR) was used to assess the gene expression of the ribosomal protein S6 kinase beta 1 (S6K1). RESULTS: In IR rats, LGZG decreased body weight and indices of hepatic steatosis. It effectively controlled blood glucose and food intake while protecting islet cells. Metabolite analysis revealed significant differences between the HFD and HFD-LGZG groups. LGZG intervention reduced branched-chain amino acid levels. Levels of IR-related metabolites such as tryptophan, alanine, taurine, and asparagine decreased significantly. IR may be linked to amino acids due to the contemporaneous increase in S6K1 expression, as shown by qRT-PCR. CONCLUSIONS: Our study strongly suggests that LGZG decoction reduces HFD-induced IR. LGZG may activate S6K1 via metabolic pathways. These findings lay the groundwork for the potential of LGZG as an IR treatment.

Interpretable machine learning models for predicting clinical pregnancies associated with surgical sperm retrieval from testes of different etiologies: a retrospective study.

BACKGROUND: The relationship between surgical sperm retrieval of different etiologies and clinical pregnancy is unclear. We aimed to develop a robust and interpretable machine learning (ML) model for predicting clinical pregnancy using the SHapley Additive exPlanation (SHAP) association of surgical sperm retrieval from testes of different etiologies. METHODS: A total of 345 infertile couples who underwent intracytoplasmic sperm injection (ICSI) treatment with surgical sperm retrieval due to different etiologies from February 2020 to March 2023 at the reproductive center were retrospectively analyzed. The six machine learning (ML) models were used to predict the clinical pregnancy of ICSI. After evaluating the performance characteristics of the six ML models, the Extreme Gradient Boosting model (XGBoost) was selected as the best model, and SHAP was utilized to interpret the XGBoost model for predicting clinical pregnancies and to reveal the decision-making process of the model. RESULTS: Combining the area under the receiver operating characteristic curve (AUROC), accuracy, precision, recall, F1 score, brier score, and the area under the precision-recall (P-R) curve (AP), the XGBoost model has the best performance (AUROC: 0.858, 95% confidence interval (CI): 0.778-0.936, accuracy: 79.71%, brier score: 0.151). The global summary plot of SHAP values shows that the female age is the most important feature influencing the model output. The SHAP plot showed that younger age in females, bigger testicular volume (TV), non-tobacco use, higher anti-müllerian hormone (AMH), lower follicle-stimulating hormone (FSH) in females, lower FSH in males, the temporary ejaculatory disorders (TED) group, and not the non-obstructive azoospermia (NOA) group all resulted in an increased probability of clinical pregnancy. CONCLUSIONS: The XGBoost model predicts clinical pregnancies associated with testicular sperm retrieval of different etiologies with high accuracy, reliability, and robustness. It can provide clinical counseling decisions for patients with surgical sperm retrieval of various etiologies.

Effect of microwaves combined with peracetic acid to improve the dewatering performance of residual sludge.

The activated sludge process plays a crucial role in modern wastewater treatment plants. During the treatment of daily sewage, a large amount of residual sludge is generated, which, if improperly managed, can pose burdens on the environment and human health. Additionally, the highly hydrated colloidal structure of biopolymers limits the rate and degree of dewatering, making mechanical dewatering challenging. This study investigates the impact and mechanism of microwave irradiation (MW) in conjunction with peracetic acid (PAA) on the dewatering efficiency of sludge. Sludge dewatering effectiveness was assessed through capillary suction time (CST) and specific resistance to filtration (SRF). Examination of the impact of MW-PAA treatment on sludge dewatering performance involved assessing the levels of extracellular polymeric substances (EPS), employing three-dimensional excitation-emission matrix (3D-EEM), Fourier transform-infrared spectroscopy (FT-IR), and scanning electron microscopy. Findings reveal that optimal dewatering performance, with respective reductions of 91.22% for SRF and 84.22% for CST, was attained under the following conditions: microwave power of 600 W, reaction time of 120 s, and PAA dosage of 0.25 g/g MLSS. Additionally, alterations in both sludge EPS composition and floc morphology pre- and post-MW-PAA treatment underwent examination. The findings demonstrate that microwaves additionally boost the breakdown of PAA into •OH radicals, suggesting a synergistic effect upon combining MW-PAA treatment. These pertinent research findings offer insights into employing MW-PAA technology for residual sludge treatment.

Validation of the "obturator functioning scale" for Chinese-speaking patients with obturator prostheses after cancer-related maxillectomy.

Objective: The Obturator Functioning Scale (OFS) is a scale without formal measures of validity in any language. This study aimed to translate and adapt the OFS from English to Chinese and check its reliability and validity in Chinese-speaking patients with obturator prostheses after cancer-related maxillectomy. Methods: The 15-item Chinese preversion of the OFS was completed by 133 patients in three tertiary stomatological hospitals. Of these, 41 completed it again one week after the first measurement. The patients also completed the Chinese version of the University of Washington quality of life scale (UW-QOL, Version 4). Results: Item 12 ("upper lip feels numb") was deleted to achieve a better statistical fit. The 14-item Chinese version of the OFS (OFS-Ch) demonstrated high internal consistency (Cronbach's alpha = 0.908). The test-retest reliability coefficients for most items exceeded 0.90, indicating substantial reproducibility. Confirmatory factor analysis found that the scale consisted of three correlated factors: 1) eating (four items), 2) speech (five items), and 3) other problems (five items). This explained 70.2 % of the total variance using exploratory factor analysis. The scale was significantly convergent and discriminant and could validly discriminate between patients with Brown I and IId maxillary defects. Conclusions: Our results showed that the OFS-Ch scale is a valid tool for evaluating oral dysfunction and satisfaction with appearance for patients with the obturator prosthesis and identifying those at risk of poor obturator function in clinical settings.

Naringin acts as a TRPV1 antagonist to attenuate UVB-induced senescence and damage in HaCaT cells.

This study aimed to explore the mechanism of naringin (Nar) in alleviating ultraviolet B (UVB)-induced HaCaT cell senescence and damage. Human keratinocytes (HaCaT cells) were divided into control, UVB, UVB + Nar, UVB + Cap, and UVB + Nar + Cap groups. Analysis was performed using the MTT assay to assess cell viability, flow cytometry to measure the apoptosis level, SA-ß-Gal staining to observe cellular senescence, and Western blot to assess protein levels of TRPV1, p16, p53, p21, matrix metalloproteinase (MMP)-1, and MMP-9. Both UVB irradiation and capsaicin (Cap) treatment upregulated the expression of TRPV1 in HaCaT cells, inhibited cell proliferation, promoted apoptosis, and increased the expression of p16, p53, p21, MMP-1, and MMP-9. Nar treatment reversed the above effects via inhibition of TRPV1 expression, thereby relieving senescence and cell damage induced by UVB irradiation. Taken together, these findings suggest that Nar can reduce UVB-induced senescence and damage in HaCaT cells by acting as an antagonist of TRPV1.

A population-based study of Helicobacter pylori: Does asymptomatic infection mean no gastroscopic lesions?

OBJECTIVES: We determined the common clinical characteristics of patients infected with Helicobacter pylori (H. pylori) and investigated the relationship between H. pylori infection, and clinical symptoms, and gastroscopic manifestations. Our focus was specifically on the clinical manifestations in asymptomatic patients. METHODS: We obtained the physical examination data of patients who underwent the 14C urea breath test between January 2018 and December 2020 at our Hospital. Basic demographic data, questionnaire data on clinical symptoms, and clinical examination data of the patients were also collected, and the correlation analysis was performed. RESULTS: A total of 2863 participants were included in the study. The overall H. pylori infection rate was 26.30%. The clinical symptoms between H. pylori-positive patients and H. pylori-negative patients did not differ significantly (P > .05). However, H. pylori-positive patients exhibited more severe gastroscopic manifestations (P < .001). The 14C urea breath test disintegrations per minute (DPM) values in H. pylori-positive patients correlated with their serum pepsinogen and gastrin-17 levels. With an increase in the DPM value, more combinations of clinical symptoms appeared in the patients. Among H. pylori-positive patients, DPM levels in asymptomatic patients were lower than those in symptomatic patients (P < .001). However, gastroscopic manifestations did not vary significantly between asymptomatic and symptomatic patients (P > .05). CONCLUSION: Patients infected with H. pylori showed no specific gastrointestinal symptoms. Patients with asymptomatic infection showed lower DPM levels, but their gastroscopic manifestations were similar to those of patients with symptomatic infection, and their lesions were more severe than H. pylori-negative people.

Microencapsulation of Bifidobacterium bifidum F-35 via modulation of emulsifying technique and its mechanical effects on the rheological stability of set-yogurt.

Microencapsulation of B. bifidum F-35 was carried out through emulsification technique in order to increase the microbial load while maintaining the rheological functions of set-yogurt. To produce single-layer (SL) microcapsules of whey protein, the pH was adjusted to 6.4 within Transglutaminase-induced gelation. Sodium alginate was processed as the external layer using calcium-induced gelation (pH 5.5) to produce the double-layer (DL) microcapsule. Scanning electron microscopy revealed that SL and DL microcapsules had sizes of 10 and 280 µm, respectively. The highest microbial load was clearly visible in the DL sample. According to texture profile analysis, the DL sample had the highest levels of gumminess, chewiness, and adhesiveness. The free sample outperformed the encapsulated samples in terms of springiness and cohesiveness. Although the SL sample had the highest viscosity, it produced a deformed gel when firmness was measured. In terms of firmness, the DL sample performed quite well. The viability of encapsulated B. bifidum F-35 in DL was higher than SL microcapsules during storage. Microencapsulation of B. bifidum F-35 with whey protein and sodium alginate is a promising technique that could improve the rheological properties of set-yogurt as a popular vehicle for bioactive ingredients.

The effect of secukinumab treatment for psoriasis on serum cytokines and correlation with disease severity.

OBJECTIVE: To investigate the effects of secukinumab treatment for psoriasis on different functional cytokines and inflammatory mediators in patients' serum METHODS: Enzyme-linked immunosorbent assay was used to detect interleukin (IL)-1ß and IL-1RA associated with intrinsic immunity; IL-6, IL-18, and growth regulated oncogene alpha (GROα) associated with neutrophils; IL-12, tumour necrosis factor (TNF)-α, and interferon (IFN)-γ associated with Th1; IL-23, IL-17A, and IL-22 associated with Th17; Thymus activation regulated chemokine (TARC), IL-13, and defensin beta 2 (DEFB2) associated with Th2; Vascular endothelial growth factor (VEGF)-A and IL-10 associated with angiogenesis; and IFN-γ associated with sepsis in the peripheral blood of 12 patients with common psoriasis treated with secukinumab and 15 healthy controls. IL-23, IL-17A, IL-22 associated with Th17; TARC, IL-13, DEFB2 associated with Th2; VEGF-A, IL-10 associated with angiogenesis and procalcitonin (PCT) associated with sepsis. The differences in expression of the above cytokines before and after treatment and the correlation with psoriasis disease severityï¼»Psoriasis Area Severity Index(PASI) scoreï¼½, age, and disease duration were analyzed. RESULTS: The mean PASI score of the enrolled patients with moderate to severe psoriasis was 21.6 ± 11.0 before treatment and decreased to below 1 after treatment. Serum IL-6; IL-18, GROα, IFN-γ, TNF-α, VEGF-A, and IL-17A were significantly higher than normal. And IL-17A and IFN-γ were positively correlated with disease duration and age, and IL-18 was positively correlated with PASI score. The expression levels of IL-6, GROα, VEGF-A, IFN-γ, TNF-α, IL-17A and IL-23 were significantly lower after secukinumab treatment compared with those before treatment, but the expression levels of IFN-γ, VEGF-A, TARC, IL-13, and DEFB2 were still significantly higher than those of normal subjects after treatment CONCLUSIONS: secukinumab clears skin lesions by antagonizing IL-17A and simultaneously decreasing the expression levels of IL-6, GRO α, VEGF-A, IFN-γ, TNF-α, IL-17A, and IL-23.

Subtractionless compressed-sensing-accelerated whole-body MR angiography using two-point Dixon fat suppression with single-pass half-reduced contrast dose: feasibility study and initial experience.

PURPOSE: To investigate the feasibility and clinical utility of a compressed-sensing-accelerated subtractionless whole-body MRA (CS-WBMRA) protocol with only contrast injection for suspected arterial diseases, by comparison to conventional dual-pass subtraction-based whole-body MRA (conventional-WBMRA) and available computed tomography angiography (CTA). MATERIALS AND METHODS: This prospective study assessed 86 patients (mean age, 56 years ± 16.4 [standard deviation]; 25 women) with suspected arterial diseases from May 2021 to December 2022, who underwent CS-WBMRA (n = 48, mean age, 55.9 years ± 16.4 [standard deviation]; 25 women) and conventional-WBMRA (n = 38, mean age, 48 years ± 17.4 [standard deviation]; 20 women) on a 3.0 T MRI after random group assignment based on the chronological order of enrolment. Of all enrolled patients administered the CS-WBMRA protocol, 35% (17/48) underwent CTA as required by clinical demands. Two experienced radiologists independently scored the qualitative image quality and venous enhancement contamination. Quantitative image assessment was carried out by determining and comparing the apparent signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) of four representative arterial segments. The total examination time and contrast-dose were also recorded. The independent samples t-test or the Wilcoxon rank sum test was used for statistical analysis. RESULTS: The overall scores of CS-WBMRA outperformed those of conventional-WMBRA (3.40 ± 0.60 vs 3.22 ± 0.55, P < 0.001). In total, 1776 and 1406 arterial segments in the CS-WBMRA and conventional-WBMRA group were evaluated. Qualitative image scores for 7 (of 15) vessel segments in the CS-WMBRA group had statistically significantly increased values compared to those of the conventional-WBMRA groups (P < 0.05). Scores from the other 8 segments showed similar image quality (P > 0.05) between the two protocols. In the quantitative analysis, overall apparent SNRs were significantly higher in the conventional-WBMRA group than in the CS-WBMRA group (214.98 ± 136.05 vs 164.90 ± 118.05; P < 0.001), while overall apparent CNRs were not significantly different in these two groups (CS vs conventional: 107.13 ± 72.323 vs 161.24 ± 118.64; P > 0.05). In the CS-WBMRA group, 7 of 1776 (0.4%) vessel segments were contaminated severely by venous enhancement, while in the convention-WBMRA group, 317 of 1406 (23%) were rated as severe contamination. In the CS-WBMRA group, total examination and reconstruction times were only 7 min and 10 min, respectively, vs 20 min and < 30 s for the conventional WBMRA group, respectively. The contrast agent dose used in the CS-WBMRA protocol was reduced by half compared to conventional-WBMRA protocol (18.7 ± 3.5 ml vs 37.2 ± 5.4 ml, P = 0.008). CONCLUSION: The CS-WBMRA protocol provides excellent image quality and sufficient diagnostic accuracy for whole-body arterial disease, with relatively faster workflow and half-dose reduction of contrast agent, which has greater potential in clinical practice compared with conventional-WBMRA.

The Efficacy and Cognitive Impact of Perampanel Monotherapy in Patients with Self-Limited Epilepsy with Centrotemporal Spikes: A Retrospective Analysis.

Objective: The third generation of antiepileptic medication (ASM) perampanel (PER), is mostly used as an add-on treatment for refractory epilepsy patients, and rarely used as a monotherapy. This study aims to observe the efficacy and assess the cognitive effects of PER monotherapy in patients with self-limited epilepsy with centrotemporal spikes (SeLECTS). Patients and Methods: Through screening, 86 patients who were first diagnosed with SeLECTS and treated with PER monotherapy were included in this study. All patients were followed up at least 12 months, and Evaluated the efficacy and safety of PER by observing the seizures of patients. At the same time, we used the P300 event-related potential (ERP) component and Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) to evaluate the cognitive changes in children before and after treatment with PER. Results: Ten percent of the children experienced adverse effects, such as dizziness, gait instability, and irritability. The drug retention rate at the last follow-up was 98.83%. Further more, the P300 ERP component and WISC-IV tests were performed no significant difference before and 12 months after PER monotherapy in SeLECTS children. Conclusion: The third-generation of ASM PER monotherapy had a clear effect in children with SeLECTS. A small dose of PER can control seizures well and has no obvious effect on cognitive development.

Epidemiological and clinical features of hypertrophic scar and keloid in Chinese college students: A university-based cross-sectional survey.

Background: Hypertrophic scar (HS) and keloid (KD) are common dermal fibroproliferative growth caused by pathological wound healing. HS's prevalence is currently undetermined in China. Though it primarily occurs in dark-skinned individuals, KD can develop in all races, and its prevalence among Chinese people is poorly documented. Objective: To explore the present epidemiological status of them in Chinese college students. Methods: We conducted a university-based cross-sectional study at one university in Fujian, China. A total of 1785 participants aged 16-34 years (mean age, 20.0 ± 2.0; 58.7% female) were enrolled and statistical analyses were performed. Results: HS and KD were observed in 5.2% (95% confidence interval [CI]: 4.2-6.2) and 0.6% (95% CI: 0.3-1.0) of the population respectively. There was a significant difference by sex in HS (P < 0.05), but not in KD. The prevalence of HS and KD both showed a significant difference by age (P < 0.05), but not in ethnic and native place distribution. The occurrence of HS and KD were both concentrated in individuals 9-20 years old (HS: 77.2%; KD: 81.8%). They were mainly distributed in the upper limbs (52.1%; 64.3%), and the main cause was trauma (51.0%; 35.7%). In addition, male sex was a risk factor for HS (adjusted P < 0.001), and KD was associated with age ≥22 years and family history (adjusted P < 0.050). Conclusion: HS and KD are common in Chinese college students, and more attention and research is warranted.

Mesenchymal Stem Cells Promote Intestinal Mucosal Repair by Positively Regulating the Nrf2/Keap1/ARE Signaling Pathway in Acute Experimental Colitis.

BACKGROUND/AIMS: Mesenchymal stem cells (MSCs) are a type of adult pluripotent stem cell that has anti-inflammatory and immunomodulatory effects, and whose conditioned medium (CM) has also been found to be effective. We used MSC and CM enemas to investigate their ameliorative effects in a mouse model of colitis. METHODS: We employed MSCs, CM, and MSCs + ML385 (an inhibitor of Nrf2) in dextran sodium sulfate (DSS)-induced colitis. Mice were sacrificed on day 8, and the effects of MSC or CM treatment on the levels of inflammation and oxidative stress in colonic epithelial cells were evaluated by histological analyses. RESULTS: MSCs inhibited inflammatory cell infiltration and proinflammatory cytokine expression in the colon. In addition, MSCs reduced extracellular matrix deposition and maintained the mechanical barrier and permeability of colonic epithelial cells. Mechanistically, MSCs activated Nrf2, which then increased HO-1 and NQO-1 levels and downregulated the expression of Keap1 to suppress reactive oxygen species production and MDA generation, accompanied by increases in components of the enzymatic antioxidant system, including SOD, CAT, GSH-Px, and T-AOC. However, after administering an Nrf2 inhibitor (ML385) to block the Nrf2/Keap1/ARE pathway, we failed to observe protective effects of MSCs in mice with colitis. CM alone also produced some of the therapeutic benefits of MSCs but was not as effective as MSCs. CONCLUSIONS: Our data confirmed that MSCs and CM can effectively improve intestinal mucosal repair in experimental colitis and that MSCs can improve this condition by activating the Nrf2/Keap1/ARE pathway.

Chk1/2 inhibitor AZD7762 blocks the growth of preantral follicles by inducing apoptosis, suppressing proliferation, and interfering with the cell cycle in granulosa cells.

BACKGROUND: Checkpoint kinases 1/2 (Chk1/2) have an important role in somatic cell development and oocyte meiotic maturation. However, the role of Chk1/2 in folliculo-genesis has not been fully elucidated. The aim of this study was to assess the effects of Chk1/2 inhibition on ovarian folliculogenesis and granulosa cell development in mice. METHODS: Preantral follicles (100-120 µm) and granulosa cells from pre-ovulatory follicles (pre-GCs) of mice were isolated and cultured with or without Chk1/2 inhibitor AZD7762. Preantral follicles were cultured for 96h. Then, follicle morphology and fol-licular growth were assessed every 48h. Granulosa cells were cultured for 48h with or without AZD7762, after which cell apoptosis, cell proliferation, and cell cycle analysis were assessed; meanwhile, the mRNA expression of PCNA and Bax were measured by real-time RT-PCR, and PCNA and Bax protein were measured by Western blot. RESULTS: Compared with control follicles, AZD7762 inhibited growth of preantral folli-cles (P<0.05). Furthermore, inhibition of Chk1/2 significantly induced apoptosis (P<0.05) and inhibited the proliferation of granulosa cells (P<0.01), arrested cell cycle at S and G2/M phases, and decreased G1 phase fraction (P<0.001). Also, the expres-sion of PCNA mRNA and protein were reduced (P<0.01), while Bax mRNA and pro-tein were increased (P<0.05) post AZD7762 treatment in granulosa cells. CONCLUSIONS: This study revealed that Chk1 and Chk2 have a crucial role during preantral follicular development by regulating the proliferation and apoptosis of granu-losa cells.

Conditioned medium of mesenchymal stem cells pretreated with H2O2 promotes intestinal mucosal repair in acute experimental colitis.

Mesenchymal stem cells (MSCs) are a new therapeutic strategy for inflammatory bowel disease (IBD), and their efficacy has been widely recognized. However, there are still some challenges in cell therapy, including stable cell passage, laboratory conditions for cell culture, high-cost burden, and poor transplantation. The conditioned medium (CM) of MSCs is considered be an excellent alternative to cell transplantation, but the paracrine group in MSC-CM is limited in variety and low in concentration, which cannot meet the therapeutic needs of injured tissues and needs to be optimized. Pretreatment with low concentration of hydrogen peroxide (H2O2) can not only protect cells from oxidative damage, but also play a role similar to growth factors and regulate the physiological function of stem cells, to obtain an improved conditioned medium. To determine the optimal protocol for pretreatment of MSCs with H2O2, and to study the efficacy and potential mechanism of MSC-CM pretreated with H2O2 on Dextran Sulfate Sodium (DSS)-induced acute experimental colitis. MSCs were exposed to different concentrations of H2O2, and the optimal H2O2 pretreatment conditions were determined by evaluating their critical cell functional properties. H2O2-pretreated MSC-CM was transplanted into experimental mouse colitis by enema at 2, 4, and 6 days in modeling, and the changes of colonic tissue structure, the levels of inflammation and oxidative stress, the molecular changes of Nrf2/Keap1/ARE axis, and the related indicators of apoptosis in colonic epithelial cells were observed in each group. In vitro, Pretreated MSCs with 25 µM H2O2 significantly enhanced cell proliferation, migration, and survival, but had no effect on apoptosis. In vivo, MSC-CM treatment decreased apoptosis and extracellular matrix deposition, and maintained the mechanical barrier and permeability of colonic epithelial cells in experimental mouse colitis. Mechanistically, H2O2-pretreated MSC-CM against reactive oxygen species (ROS) production and MDA generation, accompanied by increases in components of the enzymatic antioxidant system includes SOD, CAT, GSH-PX, and T-AOC, which is through the up-regulation of the Nrf2, HO-1, and NQO-1 antioxidant genes. Our data confirmed that 25 µM H2O2 pretreated MSC-CM treatment could effectively improve intestinal mucosal repair in experimental colitis, which may be achieved by activating Nrf2/Keap1/ARE pathway.

Mineralogy and fluid chemistry controls on lithium isotope fractionation during clay adsorption.

Our current understanding of controls on δ7Li variability and fractionation mechanisms is limited, complicating the interpretation of chemical weathering. The role of clay adsorption in Li isotope fractionation during chemical weathering has been confirmed. However, clay assemblage and fluid chemistry are not simple and often variable in weathering settings, potentially modulating Li isotope fractionation on Earth's surface. Here, this research investigated the patterns and processes of Li isotope fractionation during adsorption on kaolinite and smectite with fluid chemistry of 0.001 M NaCl, 0.5 M NaCl, and 0.001 M Na2HPO4. Specifically, the time-dependent experiments with the reaction period up to 15 days revealed that the steady state can be achieved within one day under neutral conditions. The concentration-dependent (initial Li concentration of 2 to 1000 µM) experiments confirmed the accumulation of Li+ in smectite interlayers and adsorption of Li+ only at the external surfaces of kaolinite. Using 0.5 M NaCl solution and the desorption experiments, we hypothesize that outer-sphere Li may exist in the interlayer sites, which can be replaced by excess Na+. In comparison, inner-sphere Li+ (unexchangeable) potentially dominates at the edge surface of clays. The presence of Na2HPO4 increases the binding capacity for Li+ adsorption, in particular for kaolinite. In all cases, 6Li is enriched on clay surfaces and interlayer spaces, consistent with field observations. Fluid chemistry may affect the degree of clay Li adsorption but exerted negligible impacts on isotope fractionation. For kaolinite, a wide variation (up to 30 ‰) in isotopic fractionation between adsorbed and aqueous Li (Δ7Liaq-ad) exists, conforming to a kinetic fractionation mechanism with a constant fractionation factor αad-aq of ~0.992. By contrast, the isotopic fractionation between Li adsorbed on smectite and Li+ left in solutions keeps constant (Δ7Liaq-ad of ~5 ‰), likely following an equilibrium isotope fractionation law with an αad-aq of ~0.995.

Nitrogen deposition increases xylem hydraulic sensitivity but decreases stomatal sensitivity to water potential in two temperate deciduous tree species.

Although the effects of nitrogen deposition on tree water relations are studied extensively, its impact on the relative sensitivities of stomatal and xylem hydraulic conductance to vapor pressure deficit and water potential is still poorly understood. This study investigated the effects of a 7-year N deposition treatment on the responses of leaf water relations and sensitivity of canopy stomatal conductance to vapor pressure deficit (VPD) and water potential, as well as the sensitivity of branch hydraulic conductance to water potential in a dominant tree species (Quercus wutaishanica) and an associated tree species (Acer mono) in a temperate forest. It was found that the N deposition increased stomatal sensitivity to VPD, decreased stomatal sensitivity to water potential, and increased the vulnerability of the hydraulic system to cavitation in both species. The standardized stomatal sensitivity to VPD, however, was not affected by the N deposition, indicating that the stomata maintained the ability to regulate the water balance under nitrogen deposition condition. Although the increased stomatal sensitivity to VPD could compensate the decreased stomatal sensitivity to water potential to some extent, the combined response would increase the percentage loss of hydraulic conductivity (PLC) when 50 % loss in stomatal conductance occurred, particularly in the dominant species Q. wutaishanica. The result indicates that N deposition would increase the risk of hydraulic failure in those species if the soil and/or air becomes drier under future climate change scenarios. The results of the study can have significant implications on the modelling of ecosystem vulnerability to drought under the scenario of atmospheric nitrogen deposition.

Knockdown of Chk1 inhibits proliferation and promotes apoptosis in mouse granulosa cells and its regulation mechanism by miR-15a and miR-16.

Checkpoint kinase 1 (Chk1) is a protein kinase which preserves the genome integrity, and works as an evolutionally conserved DNA damage response and cell cycle checkpoint. However, the functional roles and regulatory mechanism of Chk1 in mouse granulosa cells (GCs) have not been fully elucidated. In this study, by RNA interfering, Chk1 gene was knocked down in GCs. Knockdown of Chk1 inhibited proliferation and increased apoptosis of GCs (p < 0.05), respectively; in addition, cell cycle of GCs was arrested at S and G2/M phases. Further qRT-PCR results showed that cell cycle factors (Cyclin B1 and Cyclin D 1) and a marker gene of proliferation (PCNA) were downregulated (p < 0.001), while apoptotic factors (p53b, p21, caspase-3, and Bax) were upregulated (p < 0.01), which suggested that knockdown of Chk1 may inhibit proliferation, regulate cell cycle, and promote apoptosis at the transcriptional level in GCs. In vitro studies showed a negative correlation between Chk1 mRNA and miR-16 expression during follicular development. To elucidate the relationship between Chk1 and miR-15a/16, luciferase reporter plasmids were constructed and luciferase assays revealed that both miR-15a and miR-16 could bind to the 3' UTR of Chk1 mRNA, and significantly downregulate the protein level of Chk1 (p < 0.01), while miR-16, not miR-15a, could significantly decrease the mRNA level of Chk1 (p < 0.05). This result indicated that miR-16 directly induced Chk1 mRNA destabilization, while miR-15a regulated Chk1 expression through translational repression. Taken together, this study uncovered the roles of Chk1 in mouse granulosa cells and its regulation by miR-15a and miR-16 through different mechanisms.

Quality of life in patients with cancer-related Brown IIb maxillary defect: A comparison between conventional obturation rehabilitation and submental flap reconstruction.

OBJECTIVES: The purpose of this retrospective study was to compare the differences in quality of life (QOL) outcomes between the conventional obturator prostheses (COP) and the pedicled submental artery island flap (SAIF) in the reconstruction of Brown IIb maxillary defects. MATERIALS AND METHODS: The QOL of 116 eligible patients who had a lapse ≥ 12 months after the cancer-related maxilla ablation was evaluated by the University of Washington quality of life scale (UW-QOL), Performance Status Scale for Head and Neck (PSS-HN), and Obturator Functioning Scale (OFS). RESULTS: Patients in the SAIF group reported statistically and clinically significant higher overall QOL scores but lower chewing scores in the UW-QOL scale when compared with those in the COP group (P < 0.05). Clinically significantly higher scores were also observed in the recreation and anxiety domains in the UW-QOL scale for the SAIF group, but there was no statistical significances. The COP group reported more complaints about the nasal leakage when swallowing and the shape of the upper lip, and had a stronger willingness to avoid family or social events in the OFS (P < 0.05). CONCLUSIONS: For patients with Brown IIb defects, SAIF reconstruction can achieve reduced nasal leakage when swallowing, improved upper-lip contour, increased social activity, and superior overall QOL than COP. The inferior chewing function in the SAIF group indicated the need for dental rehabilitation with a conventional denture or osseointegrated implants.

MicroRNAs miR-14 and miR-2766 regulate tyrosine hydroxylase to control larval-pupal metamorphosis in Helicoverpa armigera.

BACKGROUND: The cotton bollworm, Helicoverpa armigera, is a worldwide polyphagous pest, causing huge economic losses in vegetable, cotton and corn crops, among others. Owing to long-term exposure to Bacillus thuringiensis (Bt) toxins, evolution of resistance has been detected in this pest. As a conservative and effective neurotransmitter, dopamine (DA) has an important role in insect growth and development. In this study, we investigated the regulatory functions of DA and its associated non-coding RNA in metamorphosis in H. armigera. RESULTS: Expression profiles indicated that DA and DA pathway genes were highly expressed during larval-pupal metamorphosis in H. armigera. RNA interference and pharmacological experiments confirmed that tyrosine hydroxylase (TH), dopa decarboxylase, vesicular amine transporter and DA receptor 2 are critical genes related to the development of H. armigera from larvae to pupae. We also found that miR-14 and miR-2766 targeted the 3' untranslated region to post-transcriptionally regulate HaTH function. Application of miR-2766 and miR-14 antagomirs significantly increased levels of HaTH transcripts and proteins, while injection of miR-2766 and miR-14 agomirs not only suppressed messenger RNA and protein levels of HaTH, but also resulted in defective pupation in H. armigera. CONCLUSION: These results suggest that DA deficiency inhibits larval-pupal metamorphosis in H. armigera. Potentially, DA pathway genes and their microRNAs could be used as a novel target for H. armigera management. © 2022 Society of Chemical Industry.