The cGAS-STING-interferon regulatory factor 7 pathway regulates neuroinflammation in Parkinson's disease.

JOURNAL/nrgr/04.03/01300535-202508000-00026/figure1/v/2024-09-30T120553Z/r/image-tiff Interferon regulatory factor 7 plays a crucial role in the innate immune response. However, whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown. Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells. Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype. In addition, siRNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase, tumor necrosis factor α, CD16, CD32, and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1. Taken together, our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.

Reproductive outcomes after hysteroscopic adhesiolysis in patients experiencing recurrent pregnancy loss and intrauterine adhesions.

OBJECTIVE: This study aims to evaluate the reproductive outcomes after hysteroscopic adhesiolysis in patients experiencing recurrent pregnancy loss (RPL) combined with intrauterine adhesions (IUA). DESIGN: Single-center retrospective cohort study. SETTING: International referral hospital for women with IUA and RPL. PATIENTS: Between January 2018 and June 2022, a cohort of 64 women diagnosed with RPL and IUA were studied, with a follow-up period of at least one year after hysteroscopic adhesiolysis. INTERVENTIONS: All patients had a diagnosis of IUA from the diagnostic hysteroscopy and were treated with hysteroscopic adhesiolysis, utilizing intraoperative ultrasound monitoring as required. MAIN MEASUREMENTS: Live birth rate and menstrual pattern change (subjective assessment) after hysteroscopic adhesiolysis. RESULTS: In our cohort, 59.38% (38/64) achieved pregnancy following hysteroscopic adhesiolysis, with 92.11% (35/38) conceiving within two years of the procedure. The miscarriage rate was recorded at 17.19% (11/64), and the live birth rate stood at 42.19% (27/64). Throughout the extended follow-up period, 64.06% (41/64) of the patients reported increased menstrual blood volume and improvements in menstrual patterns post-hysteroscopic adhesiolysis. Univariate analysis indicated that being aged ≥35 years (P=.026), having a history of infertility (P=.003), the presence of moderate or severe IUA (P=.023), and experiencing menstrual improvements post-surgery (P=.001) were independent predictors of live birth. Multivariate analysis further identified that women with a history of infertility had a reduced chance of live birth following hysteroscopic adhesiolysis (P=.008), while those who reported menstrual pattern improvements postoperatively had an increased probability of achieving a live birth (P=.031). CONCLUSIONS: Our findings indicate that RPL and IUA patients without prior infertility and showing menstrual pattern improvement after hysteroscopic adhesiolysis, are more likely to achieve live births. Standardized hysteroscopic treatment, postoperative anti-adhesion care, and early pregnancy planning are key to improving fertility outcomes in these patients.

Octenylsuccinylation strategy to construct high-amylose maize starch-myristic acid complexes with high thermal stability, complexation efficiency and anti-retrogradation ability.

Gelatinizing high-amylose maize starch (HAMSt) requires high temperatures to allow complexation with lipids, making it a challenging process. An octenylsuccinylation method was examined as a part of a strategy to decrease the gelatinization temperature of HAMSt, thereby promoting the complexation between HAMSt and myristic acid (MAc). Octenyl succinic anhydride (OSA) modification of HAMSt reduces the onset gelatinization temperature of HAMSt from 71.63 °C to 66.97 °C. Moreover, as the OSA concentration increased from 2 % to 11 %, the degree of substitution and molecular weights of the esterified HAMSt gradually increased from 0.0069 to 0.0184 and from 0.97 × 106 to 1.17 × 106 g/mol, respectively. Fourier transform infrared analysis indicated that the octenyl-succinate groups were grafted onto the HAMSt chains. The formation of HAMSt-MAc complexes improved the thermal stability of OSA-treated HAMSt (peak temperature increased by 0.11 °C-13.95 °C). Moreover, the diffraction intensity of the V-type peak of the 11 % sample was greater than that of other samples. Finally, the anti-retrogradation ability was in the order of OSA-HAMSt-MAc complexes > HAMSt-MAc complexes > HAMSt. Overall, our results indicate that octenylsuccinylation can be an effective strategy to promote the formation of OSA-HAMSt-MAc complexes and delay starch retrogradation.

Reliability and Validity of Revised Apathy Evaluation Scale-Self in Community-Dwelling Older Adults.

OBJECTIVES: The questionnaire Apathy Evaluation Scale-Self (AES-S) has been widely adopted globally, demonstrating high reliability and validity. However, direct translation of the AES into Chinese does not fit well into the Chinese cultural setting, so a structured and comprehensive revision is needed to obtain a high reliability and validity version of the scale. METHODS: In this study, 436 adults aged ≥ 60 years from two communities in Beijing were assessed using a modified AES-S. The methodology included item analysis, exploratory factor analysis, and confirmatory factor analysis. The scale's validity was tested using the Temporal Experience of Pleasure Scale (TEPS) and Mini-Mental State Examination (MMSE). Reliability assessment included retest reliability, internal consistency reliability, and split-half reliability. RESULTS: The modified Apathy Evaluation Scale-Self-Assessment (AES-S-C) presented a first-order four-factor structure with higher reliability and validity than the original version within the Chinese older adult community. CONCLUSIONS: The revised AES-S-C is more suitable for the Chinese older adults in community settings. CLINICAL IMPLICATIONS: This self-rated scale is suitable for screening apathy among older adults in community or nursing facilities, aiding in the identification of cognitive impairment and promoting mental health.

Endothelial cell dynamics in sepsis-induced acute lung injury and acute respiratory distress syndrome: pathogenesis and therapeutic implications.

Sepsis, a prevalent critical condition in clinics, continues to be the leading cause of death from infections and a global healthcare issue. Among the organs susceptible to the harmful effects of sepsis, the lungs are notably the most frequently affected. Consequently, patients with sepsis are predisposed to developing acute lung injury (ALI), and in severe cases, acute respiratory distress syndrome (ARDS). Nevertheless, the precise mechanisms associated with the onset of ALI/ARDS remain elusive. In recent years, there has been a growing emphasis on the role of endothelial cells (ECs), a cell type integral to lung barrier function, and their interactions with various stromal cells in sepsis-induced ALI/ARDS. In this comprehensive review, we summarize the involvement of endothelial cells and their intricate interplay with immune cells and stromal cells, including pulmonary epithelial cells and fibroblasts, in the pathogenesis of sepsis-induced ALI/ARDS, with particular emphasis placed on discussing the several pivotal pathways implicated in this process. Furthermore, we discuss the potential therapeutic interventions for modulating the functions of endothelial cells, their interactions with immune cells and stromal cells, and relevant pathways associated with ALI/ARDS to present a potential therapeutic strategy for managing sepsis and sepsis-induced ALI/ARDS.

Morphologic and mechanical adaptive variations in Saiga tatarica calcaneus: A model for interpreting the bone functional adaptation of wild artiodactyl in captivity.

Background and Aim: Captivity alters the locomotor behavior of wild artiodactyls and affects the mechanical loading of the calcaneus; however, the resulting adaptive changes in calcaneus morphology have not been sufficiently studied to date. This study aimed to investigate the morphological and mechanical adaptive variations in the calcaneus of Saiga tatarica to understand further the functional adaptation of the calcaneus in wild artiodactyl to captivity. Materials and Methods: Paired calcanei from autopsy samples of six captive wild artiodactyls (S. tatarica) and six domesticated artiodactyls (Ovis aries) were divided into skeletally immature and mature groups using X-ray evaluation of growth plate closure. High-resolution microcomputed tomography revealed a calcaneal diaphyseal cross-section. The mechanical and nanomorphological characteristics of the trabecular bone were determined by atomic force microscopy. Results: The percent cortical bone area (%CA), cortical thickness ratio (CTR), and Young's modulus (E) differed between species in the immature groups but not in the mature groups. S. tatarica had significantly higher growth rates for %CA, CTR, and E in the mid-shaft than O. aries (p < 0.05). Conclusion: The calcaneus morphology of S. tatarica converges with that of domesticated O. aries during ontogeny. These results indicate that the calcaneus of wild artiodactyls can undergo potentially transitional changes during the short-term adaptation to captivity. The above parameters can be preliminarily identified as morphological signs of functional bone adaptation in artiodactyls.

Recent progress of polymeric microneedle-assisted long-acting transdermal drug delivery.

Microneedle (MN)-assisted drug delivery technology has gained increasing attention over the past two decades. Its advantages of self-management and being minimally invasive could allow this technology to be an alternative to hypodermic needles. MNs can penetrate the stratum corneum and deliver active ingredients to the body through the dermal tissue in a controlled and sustained release. Long-acting polymeric MNs can reduce administration frequency to improve patient compliance and therapeutic outcomes, especially in the management of chronic diseases. In addition, long-acting MNs could avoid gastrointestinal reactions and reduce side effects, which has potential value for clinical application. In this paper, advances in design strategies and applications of long-acting polymeric MNs are reviewed. We also discuss the challenges in scale manufacture and regulations of polymeric MN systems. These two aspects will accelerate the effective clinical translation of MN products.

Identification, screening and taste mechanisms analysis of two novel umami pentapeptides derived from the myosin heavy chain of Atlantic cod (Gadus morhua).

Umami peptides are new ingredients for the condiment and seasoning industries, with healthy and nutrition characteristics, some of which were identified from aquatic proteins. This study aims to further explore novel umami peptides from Atlantic cod (Gadus morhua) by combining in silico, nano-HPLC-MS/MS, sensory evaluation, and electronic tongue analysis. Two novel peptides, Leu-Val-Asp-Lys-Leu (LVDKL) and Glu-Ser-Lys-Ile-Leu (ESKIL), from the myosin heavy chain of Atlantic cod (Gadus morhua), were screened and confirmed to have strong umami tastes with the thresholds of 0.427 mM and 0.574 mM, respectively. The molecular docking was adopted to explore the interactions between the umami peptides and the umami taste receptor T1R1/T1R3, which showed that the umami peptides interacted with T1R1/T1R3 mainly by electrostatic interaction, hydrogen bond interaction, and hydrophobic interaction. Furthermore, the physicochemical properties of the peptides were investigated by in silico methods and cell viability experiments. This study will provide a better understanding of the umami taste in Atlantic cod and will promote the development of condiments and seasonings.

The early development of offspring born to women with polycystic ovary syndrome: Insights from a prospective birth cohort study in Southwestern China.

PURPOSE: This prospective cohort study aimed to investigate the effect of maternal polycystic ovary syndrome (PCOS) on the offspring early development. METHODS: A total of 91 mother-child pairs, consisting of 33 PCOS and 58 non-PCOS, were recruited. Peripheral blood tests were performed during 12-16, 24-28, and 32-36 weeks of gestation. Ages & Stages Questionnaires (ASQ) were utilized to assess the motor development of offspring at 27 months of age. Logistic regression models were employed to compare groups and control confounding variables. RESULTS: Women with PCOS had a higher level of testosterone and free androgen index than the non-PCOS group in all three detection windows. There were no intergroup differences in any of the five domains of specific ASQ domain scores or the body measurements of the offspring at 27 months old. Stratification by sex of offspring suggested that no significant differences were detected in the male offspring. However, in the female offspring, the PCOS group exhibited lower gross motor scores in female offspring than the non-PCOS group (48.1 ± 11.8 vs. 55.2 ± 8.1, P = 0.027), as well as lower fine motor scores (48.5 ± 8.5 vs. 53.6 ± 11.0, P = 0.028). The gross motor score of female offspring in the PCOS group remained lower even after adjustments. Each 1 ng/mL increase in testosterone at 12-16 weeks of gestation was associated with a decrease in gross motor score of female offspring by 12.2 (95% CI = -23.3 to -1.0, P = 0.038). The highest tertile of testosterone at 12-16 weeks of gestation was associated with a 7.75-point decrease in gross motor score of female offspring compared to the lowest tertile of testosterone (95% CI = -14.9 to -0.6, P = 0.040), with a significant linear trend observed (P for trend = 0.031). CONCLUSIONS: The findings of this study suggest that maternal PCOS could exert a negative influence on the gross motor development of female offspring, potentially associated with intrauterine androgen exposure during the early stages of pregnancy.

Reducing polypyrimidine tract­binding protein 1 fails to promote neuronal transdifferentiation on HT22 and mouse astrocyte cells under physiological conditions.

In contrast to prior findings that have illustrated the conversion of non-neuronal cells into functional neurons through the specific targeting of polypyrimidine tract-binding protein 1 (PTBP1), accumulated evidence suggests the impracticality of inducing neuronal transdifferentiation through suppressing PTBP1 expression in pathological circumstances. Therefore, the present study explored the effect of knocking down PTBP1 under physiological conditions on the transdifferentiation of mouse hippocampal neuron HT22 cells and mouse astrocyte (MA) cells. A total of 20 µM negative control small interfering (si)RNA and siRNA targeting PTBP1 were transfected into HT22 and MA cells using Lipo8000™ for 3 and 5 days, respectively. The expression of early neuronal marker ßIII-Tubulin and mature neuronal markers NeuN and microtubule-associated protein 2 (MAP2) were detected using western blotting. In addition, ßIII-tubulin, NeuN and MAP2 were labeled with immunofluorescence staining to evaluate neuronal cell differentiation in response to PTBP1 downregulation. Under physiological conditions, no significant changes in the expression of ßIII-Tubulin, NeuN and MAP2 were found after 3 and 5 days of knockdown of PTBP1 protein in both HT22 and MA cells. In addition, the immunofluorescence staining results showed no apparent transdifferentiation in maker levels and morphology. The results suggested that the knockdown of PTBP1 failed to induce neuronal differentiation under physiological conditions.

Network of depressive symptoms before and after a diagnosis of chronic kidney disease.

OBJECTIVE: A diagnosis of chronic kidney disease (CKD) may increase the risk for depression. The network perspective focuses on dynamic relationships among individual symptoms, which could advance our understanding of the development of depression during the transition to a diagnosis of CKD. The aim of this study was to use network analysis to examine the longitudinal associations of depressive symptoms from before to after a diagnosis of CKD. METHOD: The analytic sample included 1,386 participants from the Chinese Health and Retirement Longitudinal Study. Participants were aged 45 years or older and reported a doctor's diagnosis of CKD in any wave of interviews between 2011 and 2018. Depressive symptoms were measured by the 10-item version of the Center for Epidemiological Studies Depression. Cross-lagged panel network analysis was conducted to examine relationships between symptoms at three time points: prediagnosis; onset of diagnosis, and postdiagnosis). RESULTS: After controlling for other symptoms and covariates, feeling unable to get going and less happiness at prediagnosis were the most predictive of other symptoms at the diagnosis of CKD. Feeling effortful to do everything and depressed mood at the diagnosis of CKD were the most predictive of other symptoms at postdiagnosis. CONCLUSIONS: Fatigue (i.e., feeling unable to get going, feeling effortful to do everything), less happiness, and depressed mood were central symptoms during the transition to a diagnosis of CKD. These findings highlight the benefits of identifying and managing these central symptoms to reduce the risk of activating other depressive symptoms. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Patient-derived organoids facilitating individual therapy in an adolescent with embryonal rhabdomyosarcoma of the cervix: a case report and literature review.

Rhabdomyosarcoma (RMS) is a highly aggressive pediatric neoplasm that originates from striated muscle or undifferentiated mesenchymal cells. Based on its histopathological characteristics, the World Health Organization categorizes RMS into four distinct subtypes: embryonal RMS, alveolar RMS, pleomorphic RMS, and sclerosing/spindle cell RMS. Embryonal RMS represents the predominant subtype and primarily manifests in the head and neck region, with the genitourinary system being the subsequent most frequent site of occurrence. Embryonal rhabdomyosarcoma of the cervix (cERMS) is more insidious in the reproductive tract, and there is still a lack of consensus on its treatment. Patient-derived organoids (PDOs) are being prioritized for use in guiding personalized medicine. The application of PDOs to test the sensitivity of chemotherapy drugs in patients with cERMS has rarely been reported. In this case report, we delineate the presentation and diagnosis of a 16-year-old adolescent with cERMS, emphasizing the utilization of PDOs in the management of this infrequent neoplasm. We intend to elucidate the diagnostic and therapeutic processes associated with cERMS by referencing previously reported literature on this infrequent tumor, aiming to offer a foundation for clinical practice.

Involvement of CXCL10 in Neuronal Damage under the Condition of Spinal Cord Injury and the Potential Therapeutic Effect of Nrg1.

OBJECTIVE: Few studies have reported the direct effect of C-X-C motif chemokine ligand 10 (CXCL10) and Neuregulin 1 (Nrg1) on neurons after spinal cord injury (SCI). This study reports the role of CXCL10 in the regulation of neuronal damage after SCI and the potential therapeutic effect of Nrg1. METHODS: The expression level of CXCL10 and Nrg1 in SCI mice was analyzed in the Gene Expression Omnibus DataSets, followed by immunohistochemical confirmation using a mouse SCI model. HT22 cells and NSC34 cells were treated with CXCL10 and Nrg1, individually or in combination, and then assayed for cell viability. The percentage of wound closure was determined through the cell scratch injury model using HT22 and NSC34 cells. Potential molecular mechanisms were also tested in response to either the individual administration of CXCL10 and Nrg1 or a mixture of both molecules. RESULTS: CXCL10 expression was significantly increased in both young and old mice subjected to SCI, while Nrg1 expression was significantly decreased. CXCL10 induced a decrease in cell viability, which was partially reversed by Nrg1. CXCL10 failed to inhibit scratch healing in HT22 and NSC34 cells, while Nrg1 promoted scratch healing. At the molecular level, CXCL10-activated cleaved caspase 9 and cleaved caspase 3 were both inhibited by Nrg1 through pERK1/2 signaling in HT22 and NSC34 cells. CONCLUSIONS: CXCL10 is upregulated in SCI. Despite the negative effect on cell viability, CXCL10 failed to inhibit the scratch healing of HT22 and NSC34 cells. Nrg1 may protect neurons by partially antagonizing the effect of CXCL10.

Effect of vitamin D supplementation on hormones and menstrual cycle regularization in polycystic ovary syndrome women: A systemic review and meta-analysis.

AIM: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disease among women of childbearing age. Women with PCOS frequently experience reproductive complications, which are closely associated with the concentration of vitamin D. This systemic review and meta-analysis were conducted to elucidate the possible effect of vitamin D supplementation in PCOS women on hormones, including Luteinizing hormone (LH), follicle-stimulating hormone (FSH), the ratio of LH and FSH (LH/FSH), and the menstrual cycle regularization. METHODS: We searched PubMed, Web of Science, Ovid MEDLINE, Cochrane Library, and EMBASE for the relevant articles published up to January 2022. The pooled estimates were calculated using RevMan 5.4 software. RESULTS: Twelve studies involving 849 PCOS patients were included. Our study indicated that vitamin D supplementation could reduce serum LH (standard mean difference [SMD]: -0.41; 95% confidence interval [CI]: -0.54, -0.28; p < 0.01). Subgroup analysis identified that the supplementation of vitamin D ≤4000 IU/day (SMD: -0.69; 95% CI: -1.15, -0.23; p < 0.01), treatment time ≤8 weeks (SMD: -0.61; 95% CI: -0.95, -0.26; p < 0.01), and vitamin D co-supplementation (SMD: -0.37; 95% CI: -0.65, -0.10; p < 0.01) were related to reduce serum LH level. In addition, vitamin D supplementation improved the regularity of menstrual cycle significantly (risk ratio [RR]: 1.35; 95% CI: 1.18, 1.54; p < 0.01). In stratified analysis, the significant effects only existed in dosage of vitamin D >4000 IU (RR: 1.62; 95% CI: 1.02, 2.57; p < 0.01), treatment time >8 weeks (RR: 1.41; 95% CI: 1.06, 1.87; p = 0.02) and vitamin D co-supplementation (RR: 1.18; 95% CI: 1.03, 1.35; p = 0.02). However, vitamin D might have no effects on serum FSH (SMD: -0.05; 95% CI: -0.42, 0.32; p = 0.79) and LH/FSH (SMD: -0.24; 95% CI: -0.55, 0.08; p = 0.14) in PCOS patients. CONCLUSIONS: Evidence from the existing randomized controlled trials indicated that vitamin D supplementation might improve the LH level and the menstrual cycle regularization but did not have any effect on FSH and LH/FSH levels in PCOS patients.

Effects of ethanol pretreatment on osteogenic activity and off-flavors in blue mussel (Mytilus edulis L.) enzymatic hydrolysates.

Aquatic protein hydrolysates have many biological activities, but the off-flavor seriously decreases their commercial acceptability. Therefore, it is important to invest in finding an effective deodorization of aquatic hydrolysates that do not affect activities. In this study, ethanol pretreatment of mussel was applied to establish a new method to deodorize the blue mussel (Mytilus edulis L.) hydrolysates. LC-MS and GC-MS analysis results showed that 87.34% of fatty acids, 83.94% of aldehydes, most volatile flavor compounds including aldehydes, ketones, alcohols, acids, and hydrocarbons were decreased after ethanol pretreatment. Besides, it was found that the enzymatic hydrolysates of mussel with or without ethanol pretreatment showed high osteogenic activity, which induced an increase of 33.65 ± 4.36% and 31.77 ± 5.45% in MC3T3-E1 cell growth. These results suggest that ethanol pretreatment has beneficial potential for improving the flavor aspects of blue mussel peptides which may have the potential to stimulate bone regeneration and formation.

Existence of chronic endometritis and its influence on pregnancy outcomes in infertile women with minimal/mild endometriosis.

OBJECTIVE: This study aimed to evaluate the prevalence of chronic endometritis (CE) in women with minimal/mild endometriosis and to analyze whether CE affects their pregnancy outcomes. METHODS: This retrospective study included 201 infertile women who were diagnosed with minimal/mild endometriosis after undergoing hysteroscopy combined with laparoscopy from January 2016 to December 2018. Immunohistochemistry was used to detect CD138 and CD38, which are specific markers of plasma cells in the endometrial stroma to diagnose CE. Subsequently, we investigated the prevalence of CE and the effects of CE on spontaneous cumulative pregnancy rate, live birth rate, and miscarriage rate within 24 months after surgery. RESULTS: The prevalence of CE in infertile women with minimal/mild endometriosis was 24.38%. Patients diagnosed with CE showed a significantly lower cumulative pregnancy rate and live birth rate compared with women without CE (46.51% vs. 71.13% [P = 0.004]; 44.19% vs. 63.38% [P = 0.025]). However, the rate of miscarriage in women with CE was also lower than in women without CE (0 vs. 7.04%, P = 0.074). CONCLUSION: Since CE had an adverse effect on cumulative pregnancy rate and live birth rate in infertile women with minimal/mild endometriosis, we suggested that diagnosis and treatment of CE may improve their pregnancy outcomes.

Role of CXCL10 in Spinal Cord Injury.

Spinal cord injury (SCI) results in acute inflammatory responses and secondary damages, including neuronal and glial cell death, axonal damage and demyelination, and blood-brain barrier (BBB) damage, eventually leading to neuronal dysfunction and other complications. C-X-C motif Chemokine Ligand 10 (CXCL10) is expressed after the injury, playing multiple roles in the development and progression of SCI. Moreover, the CXCL10 antagonist can restrict inflammatory immune responses and promote neuronal regeneration and functional recovery. In this review, we summarize the structure and biological functions of CXCL10, and the roles of the CXCL10 / CXCR3 axis in acute inflammatory responses, secondary damages, and complications during SCI, thus providing a potential theoretical basis by highlighting CXCL10 as a new potential drug target for the treatment of SCI.

MicroRNA-25-5p negatively regulates TXNIP expression and relieves inflammatory responses of brain induced by lipopolysaccharide.

Sepsis is one of the most common causes of death in patients suffering from severe infection or injury. Currently, a specific effective therapy remains to be established. In the present study, miR-25-5p, miR-105, miR-106b-5p, miR-154-3p, miR-20b-5p, miR-295-3p, miR-291-3p, miR-301b, miR-352, and miR-93-5p were predicted to target TXNIP mRNA from the databases of miRDB, Targetscan, and microT-CDS. The luciferase reporter assay confirmed that miR-25-5p negatively regulates TXNIP expression. The ELISA analyses and western blotting demonstrated that miR-25-5p downregulated the production of IL-1ß, IL-6, IL-8, and TNF-α in lipopolysaccharide (LPS)-stimulated cells or rats, as well as the protein levels of TXNIP, NLRP3, and cleaved caspase-1. In addition, miR-25-5p increased the cell viability and decreased the apoptosis in LPS-stimulated CTX TNA2 cells and reduced the abnormal morphology of the brain in LPS-stimulated rats. Besides, miR-25-5p decreased the relative mean fluorescence intensity of DCF in LPS-stimulated CTX TNA2 cell, apoptosis, and protein levels of MnSOD and catalase in LPS-stimulated brains. These findings indicate that miR-25-5p downregulated LPS-induced inflammatory responses, reactive oxygen species production, and brain damage, suggesting that miR-25-5p is a candidate treatment for septic encephalopathy.

Crosslinked biomimetic coating modified stainless-steel-mesh enables completely self-cleaning separation of crude oil/water mixtures.

The development of high-flux, durable and completely self-cleaning membranes is highly desired for separation of massive oil/water mixtures. Herein, differently crosslinked poly(2-methacryloyloxylethyl phosphorylcholine) (PMPC) brush grafted stainless steel mesh (SSM) membranes (SSM/PMPCs) were fabricated by integrating of mussel inspired universal adhesion and crosslinking chemistry with surface-initiated activators regenerated by electron transfer atom transfer radical polymerization (SI-ARGET-ATRP). The durability and self-cleaning performance of the prepared SSM membranes were evaluated by separating sticky crude oil/water mixtures in a continuous recycling dead-end filtration device. The water filtration flux driven by gravity reached 60,000 L⋅m-2⋅h-1 with a separation efficiency of over 99.98%. Furthermore, zero-flux-decline was observed during a 5 h continuous filtration when assisted by mechanical stirring. More significantly, such a completely self-cleaning separation of the well crosslinked SSM/PMPC2 membrane under optimized flux and stirring conditions had been operated cumulatively for 190 h in 30 days without any additional cleaning. These significant advances are more promising for practical applications in crude oil-contaminated water treatments and massive oil/water mixture separation.

Comprehensive Pan-Cancer Analysis of TRPM8 in Tumor Metabolism and Immune Escape.

Background: Transient receptor potential melastatin 8 (TRPM8) modulates tumor biology and sensitivity to treatment. The present study aimed to determine the part it plays in tumor immunity and physiology using pan-cancer analysis. Method: Data from the GTEx, CCLE, TISIDB, GSCA, cBioportal, and TCGA databases were collected using Estimate, Scanneo, and GSEA, and the associations between TRPM8 and prognosis, molecular subtypes, mutational burden, microsatellite instability, immune gene functions, and drug sensitivity were analyzed in 33 tumor types. Result: TRPM8 levels were found to be elevated in most tumors, particularly in solid tumors, with variations according to clinical stage. Mutation frequency was greatest in endometrial carcinoma. High levels of TRPM8 were linked to unfavorable prognosis, immune cell infiltration, and the tumor microenvironment, as well as correlating with abnormalities in the transcription levels of genes associated with immunity and DNA repair. TRPM8 was also linked to unfavorable patient outcomes and cancer-associated signaling. Conclusions: TRPM8 is strongly associated with tumor physiology and immunity. The Pan-Cancer analysis suggests the potential of TRPM8 as a treatment target or biomarker for determining the prognosis of a specific type of cancer.