Deficiency of geranylgeranyl biphosphate synthase in kidney tubules causes cystic kidney disease.

Polycystic kidney disease (PKD) is a common hereditary kidney disease. Although PKD occurrence is associated with certain gene mutations, its onset regulatory mechanisms are still not well understood. Here, we first report that the key enzyme geranylgeranyl diphosphate synthase (GGPPS) is specifically expressed in renal tubular epithelial cells of mouse kidneys. We aimed to explore the role of GGPPS in PKD. In this study, we established a Ggppsfl/fl:Cdh16cre mouse model and compared its phenotype with that of wild-type mice. A Ggpps-downregulation HK2 cell model was also used to further determine the role of GGPPS. We found that GGPPS was specifically expressed in renal tubular epithelial cells of mouse kidneys. Its expression also increased with age. Low GGPPS expression was observed in human ADPKD tissues. In the Ggppsfl/fl:Cdh16cre mouse model, Ggpps deletion in renal tubular epithelial cells induced the occurrence and development of renal tubule cystic dilation and caused the death of mice after birth due to abnormal renal function. Enhanced proliferation of cyst-lining epithelial cells was also observed after the knockout of Ggpps. These processes were related to the increased rate of Rheb on membrane/cytoplasm and hyperactivation of mTORC1 signaling. In conclusion, the deficiency of GGPPS in kidney tubules induced the formation of renal cysts. It may play a critical role in PKD pathophysiology. A novel therapeutic strategy could be designed according to this work.

Characterization and mechanism investigation of salt-activated methionine sulfoxide reductase A from halophiles.

Halophiles, thriving in harsh saline environments, capture scientific interest due to their remarkable ability to prosper under extreme salinity. This study unveils the distinct salt-induced activation of methionine sulfoxide reductases (MsrA) from Halobacterium hubeiense, showcasing a significant enhancement in enzymatic activity across various salt concentrations ranging from 0.5 to 3.5 M. This contrasts sharply with the activity profiles of non-halophilic counterparts. Through comprehensive molecular dynamics simulations, we demonstrate that salt ions stabilize and compact the enzyme's structure, notably enhancing its substrate affinity. Mutagenesis analysis further confirms the essential role of salt bridges formed by the basic Arg168 residue in salt-induced activation. Mutating Arg168 to an acidic or neutral residue disrupts salt-induced activation, substantially reducing the enzyme activity under salt conditions. Our research provides evidence of salt-activated MsrA activity in halophiles, elucidating the molecular basis of halophilic enzyme activity in response to salts.

Synthesis of Chiral Sulfoxides by A Cyclic Oxidation-Reduction Multi-Enzymatic Cascade Biocatalysis.

Optically pure sulfoxides are valuable organosulfur compounds extensively employed in medicinal and organic synthesis. In this study, we present a biocatalytic oxidation-reduction cascade system designed for the preparation of enantiopure sulfoxides. The system involves the cooperation of a low-enantioselective chimeric oxidase SMO (styrene monooxygenase) with a high-enantioselective reductase MsrA (methionine sulfoxide reductase A), facilitating "non-selective oxidation and selective reduction" cycles for prochiral sulfide oxidation. The regeneration of requisite cofactors for MsrA and SMO was achieved via a cascade catalysis process involving three auxiliary enzymes, sustained by cost-effective D-glucose. Under the optimal reaction conditions, a series of heteroaryl alkyl, aryl alkyl and dialkyl sulfoxides in R configuration were synthesized through this "one-pot, one step" cascade reaction. The obtained compounds exhibited high yields of >90 % and demonstrated enantiomeric excess (ee) values exceeding 90 %. This study represents an unconventional and efficient biocatalytic way in utilizing the low-enantioselective oxidase for the synthesis of enantiopure sulfoxides.

Engineering of methionine sulfoxide reductase A with simultaneously improved stability and activity for kinetic resolution of chiral sulfoxides.

Methionine sulfoxide reductase A (MsrA) has emerged as promising biocatalysts in the enantioselective kinetic resolution of racemic (rac) sulfoxides. In this study, we engineered robust MsrA variants through directed evolution, demonstrating substantial improvements of thermostability. Mechanism analysis reveals that the enhanced thermostability results from the strengthening of intracellular interactions and increase in molecular compactness. Moreover, these variants demonstrated concurrent improvements in catalytic activities, and notably, these enhancements in stability and activity collectively contributed to a significant improvement in enzyme substrate tolerance. We achieved kinetic resolution on a series of rac-sulfoxides with high enantioselectivity under initial substrate concentrations reaching up to 93.0 g/L, representing a great improvement in the aspect of the substrate concentration for biocatalytic preparation of chiral sulfoxide. Hence, the simultaneously improved thermostability, activity and substrate tolerance of MsrA represent an excellent biocatalyst for the green synthesis of optically pure sulfoxides.

Kinetic resolution of sulfoxides with high enantioselectivity using a new homologue of methionine sulfoxide reductase B.

Optically pure sulfoxides are noteworthy compounds that find wide applications in various industrial fields. Here, we report a methionine sulfoxide reductase B (MsrB) homologue that exhibits high enantioselectivity and broad substrate scope for the kinetic resolution of racemic (rac) sulfoxides. This MsrB homologue, named liMsrB, was identified from Limnohabitans sp. 103DPR2 and showed good activity together with enantioselectivity towards a series of aromatic, heteroaromatic, alkyl and thioalkyl sulfoxides. Chiral sulfoxides in the S configuration were prepared in approximately 50% yield and 92-99% enantiomeric excess through kinetic resolution at an initial substrate concentration of up to 90 mM (11.2 g L-1). This study presents an efficient route for the enzymatic preparation of (S)-sulfoxides through kinetic resolution.

Aramid nanofibers supported metal-organic framework aerogel for protection of chemical warfare agent.

Protective fabrics containing Zr-Based Metal-Organic Frameworks (Zr-MOFs) show great potential in the detoxification of chemical warfare agents (CWAs). However, the current studies still face the challenges of complicated fabrication processes, limited MOF loading mass, and insufficient protection. Herein, we developed a lightweight, flexible and mechanical robust aerogel by in situ growth of UiO-66-NH2 onto aramid nanofibers (ANFs) and assembly of UiO-66-NH2 loaded ANFs (UiO-66-NH2@ANFs) into 3D hierarchically porous architecture. The UiO-66-NH2@ANF aerogels feature high MOF loading of 261 %, high surface area of 589.349 m2 g-1, open and interconnected cellular structure, which provide efficient transfer channels and promote catalytic degradation of CWAs. As a result, the UiO-66-NH2@ANF aerogels demonstrate high 2-chloroethyl ethyl thioether (CEES) removal rate at 98.9 % and a short half-life of 8.15 min. Moreover, the aerogels present good mechanical stability (recovery rate of 93.3 % after 100 cycles under 30 % strain), low thermal conductivity (λ of 25.66 mW m-1 K-1), high flame resistance (LOI of 32 %) and good wearing comfortableness, indicating promising potential in multifunctional protection against CWAs.

METTL3/YTHDF2 m6A axis promotes the malignant progression of bladder cancer by epigenetically suppressing RRAS.

The present study aimed to explore the potential roles of the methyltransferase­like 3 (METTL3)­mediated methylation of RAS related (RRAS) mRNA in the tumorigenesis and development of bladder cancer (BCa). For this purpose, the relative expression levels of METTL3 in BCa specimens and cell lines were measured using reverse transcription­quantitative PCR (RT­qPCR) and western blot analysis. The association between the METTL3 expression level and the clinical characteristics of patients with BCa was analyzed using The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis databases. Cellular experiments were performed to confirm the effects of METTL3 on the proliferative, migratory and invasive capacities of BCa cells. RT­qPCR, western blot analysis, methylated RNA immunoprecipitation (MeRIP)­qPCR and dual­luciferase report assays were utilized to verify the METTL3/RRAS/YTH N6­methyladenosine (m6A) RNA binding protein 2 (YTHDF2) regulatory axis in BCa. The results revealed that METTL3 expression was markedly increased in BCa specimens and cell lines, and was associated with poor clinical characteristics of patients with BCa. In vitro and in vivo assays demonstrated that the silencing of METTL3 markedly suppressed the proliferative, migratory and invasive capacities of BCa cells. MeRIP­PCR and dual­luciferase report assays indicated that METTL3 could bind to the m6A sites of RRAS mRNA and suppress the transcriptional activity of RRAS. YTHDF2 could recognize the m6A sites of RRAS and mediate RRAS degradation. On the whole, the findings of the present study reveal the pivotal role of METTL3­catalyzed m6A modification in BCa tumorigenesis and development. The change could facilitate BCa tumor growth and metastasis by suppressing RRAS expression in an m6A YTHDF2­dependent manner. Targeting the METTL3/RRAS/YTHDF2 regulatory axis may thus prove to be a promising strategy for the diagnosis and therapy of BCa.

Comparison of the Efficacy and Complications of Soft Ureteroscopy Lithotripsy and Percutaneous Nephrolithotomy in the Treatment of Urinary Calculi: A Systematic Review and Meta-analysis.

Objective: To systematically evaluate the efficacy and complications of soft ureteroscopic lithotripsy (SUL) and percutaneous nephrolithotomy (PCNL) in the treatment of urinary calculi and to provide evidence-proof medicine basis for the popularization and application of flexible ureteroscopic lithotripsy. Methods: PubMed, EMBASE, ScienceDirect, Cochrane Library, China knowledge Network Database (CNKI), China VIP Database, Wanfang Database, and China Biomedical Literature Database (CBM) were searched for randomized controlled trials (RCT) related to soft ureteroscopic lithotripsy and percutaneous nephrolithotomy in the treatment of urinary calculi from Jan. 2010 to Mar. 2022. The bias risk of each included literature was assessed according to the standard of Cochrane manual 5.1.0. The collected data were meta-analyzed by RevMan 5.4 statistical software. Results: Ultimately, 6 RCT (a total of 794 samples) were included for meta-analysis. Heterogeneity test results of stone clearance rate were chi2 = 2.44, df = 5, P = 0.79 > 0.05, and I 2 = 0%, indicating none obvious heterogeneity among the included research data. The test of WMD was Z = 2.11 (P = 0.03). It could be considered that compared with PCNL in the treatment of urinary calculi, SUL had a higher stone clearance rate in patients with urolithiasis. Secondly, heterogeneity test of operation time was chi2 = 184.95, df = 5, P < 0.00001, and I 2 = 97%. The results of heterogeneity test of intraoperative blood loss displayed chi2 = 645.47, df = 5, P < 0.00001, and I 2 = 99%. Then, heterogeneity test results of postoperative hospital stay existed chi2 = 57.37, df = 5, P < 0.00001, and I 2 = 91% with an obvious heterogeneity. According to the results of this analysis, it could be considered that compared with PCNL in the treatment of urolithiasis, the operation time of SUL in the treatment of urolithiasis was longer, but the amount of intraoperative bleeding and postoperative hospital stay was significantly reduced. The results of heterogeneity of stress index level NE showed as chi2 = 0.32, df = 2, P = 0.85 > 0.05, and I 2 = 0%, and COR was chi2 = 1.09, df = 1, P = 0.30 > 0.05, and I 2 = 8%. It showed that there was no obvious heterogeneity. The heterogeneity of ACTH was chi2 = 390.36, df = 2, P < 0.00001, and I 2 = 99%, suggesting obvious heterogeneity. The test of combined effect dose WMD was Z = 21.90, 4.50, and 15.42, (P < 0.00001). It could be considered that there was a statistical difference in the WMD of stress response between patients with urinary calculi treated by soft ureteroscope and percutaneous nephrolithotomy, indicating that the stress response of patients with urinary calculi treated with SUL is less than that of PCNL. For the heterogeneity test of serum creatinine level, NE showed chi2 = 0.78, df = 2, P = 0.68 > 0.05, and I 2 = 0% without obvious heterogeneity, and the combined effect dose WMD is analyzed by random effect model. The test of combined effect dose WMD was Z = 4.22 (P < 0.00001). It can be considered that the improvement of serum creatinine level in patients with urolithiasis treated with SUL was better than that of PCNL. The results of heterogeneity test on the safety of operation are as follows: chi2 = 13.76, df = 5, P = 0.02, and I 2 = 64%, indicating obvious heterogeneity among the included research data. The combined effect dose of WMD was Z = 5.53 (P < 0.00001). This could be considered that soft ureteroscopic lithotripsy had higher safety and less postoperative complications than percutaneous nephrolithotomy in the treatment of urinary calculi. An inverted funnel chart was used to analyze the publication bias of the study with stone clearance rate as the outcome index. The results showed that the figure was not completely symmetrical and the Egger's test showed that the figure was P = 0.0005 < 0.001. It was suggested that there may be a certain degree of publication bias. Conclusion: PCNL and SUL can achieve higher stone clearance rate in the treatment of renal calculi. However, SUL has the advantages of less intraoperative bleeding, short stress reaction and postoperative hospital stay, less damage to renal function, and low incidence of complications, which is beneficial to the rapid recovery of patients after operation. More studies with higher methodological quality and longer intervention time are needed to further verify.

Hybrid nanofibrous aerogels for all-in-one solar-driven interfacial evaporation.

Solar-driven interfacial evaporation is an emerging technology to obtain fresh water using solar energy. However, the complicated system and the corresponding fabrication process severely restrict its large-scale and cost-effective production. Herein, an all-in-one solar-driven interfacial evaporator was fabricated via a hybrid nanofibrous aerogel of aramid nanofibers (ANFs), carbon nanotubes (CNTs), and gold nanoparticles (AuNPs). Assisted by the reprotonation of the ANFs, CNTs are assembled into the nanofibrous network for through-body light-to-heat activity, and AuNPs are set on the surface layer to enhance solar absorption. The aerogel also features low thermal conductivity to suppress heat losses and high capillary action to wick and confine water within the aerogels. Benefitting from the synergistic effect, the aerogel shows a high evaporation rate of 1.53 kg m-2h-1 and an evaporation efficiency of 91.3% under 1 sun irradiation. Simultaneously, the evaporator demonstrates high purification capacity for wastewaters with dyes and heavy metal ions. The integrated structure design and facile fabrication process would make the hybrid nanofibrous aerogel-based all-in-one evaporators promising for cost-effective and large-scale application under ambient solar irradiance.

Risk factors for kidney stone disease recurrence: a comprehensive meta-analysis.

BACKGROUND: Kidney stone disease (KSD) is a common illness that causes an economic burden globally. It is easy for patients to relapse once they have suffered from this disease. The reported recurrence rate of KSD ranged from 6.1% to 66.9%. We performed this meta-analysis to identify various potential risk factors for the recurrence of KSD. METHODS: The PubMed, Embase and Web of Science databases were searched using suitable keywords from inception to Mar 2022. A total of 2,663 records were collected initially. After screening the literature according to the inclusion and exclusion criteria, 53 articles (40 retrospective studies; 13 prospective studies) including 488,130 patients were enrolled. The study protocol was registered with PROSPERO (No. CRD42020171771). RESULTS: The pooled results indicated that 12 risk factors including younger age (n = 18), higher BMI (n = 16), family history of kidney stones (n = 12), personal history of kidney stones (n = 11), hypertension (n = 5), uric acid stone (n = 4), race of Caucasian (n = 3), suspected kidney stone episode before the first confirmed stone episode (n = 3), surgery (n = 3), any concurrent asymptomatic (nonobstructing) stone (n = 2), pelvic or lower pole kidney stone (n = 2), and 24 h urine test completion (n = 2) were identified to be associated with KSD recurrence. In the subgroup analysis, patients with higher BMI (OR = 1.062), personal history of nephrolithiasis (OR = 1.402), or surgery (OR = 3.178) had a higher risk of radiographic KSD recurrence. CONCLUSIONS: We identified 12 risk factors related to the recurrence of KSD. The results of this analysis could serve to construct recurrence prediction models. It could also supply a basis for preventing the recurrence of KSD.

Proton Donor-Regulated Mechanically Robust Aramid Nanofiber Aerogel Membranes for High-Temperature Thermal Insulation.

High-performance thermal insulators are urgently desired for energy-saving and thermal protection applications. However, the creation of such materials with synchronously ultralow thermal conductivity, lightweight, and mechanically robust properties still faces enormous challenges. Herein, a proton donor-regulated assembly strategy is presented to construct asymmetric aramid nanofiber (ANF) aerogel membranes with a dense skin layer and a high-porous nanofibrous body part. The asymmetric structure originates from the otherness of the structural restoration of deprotonated ANFs and the resulting ANF assembly due to the diversity of available proton concentrations. Befitting from the synergistic effect of the distinct architectures, the resulting aerogel membranes exhibit excellent overall performance in terms of a low thermal conductivity of 0.031 W·m-1·K-1, a low density of 19.2 mg·cm-3, a high porosity of 99.53%, a high tensile strength of 11.8 MPa (16.5 times enhanced), high heat resistance (>500 °C), and high flame retardancy. Furthermore, a blade-scraping process is further proposed to fabricate the aerogel membrane in a continuous and scalable manner, as it is believed to have potential applications in civil and military fields.

A new approach for reducing pollutants level: a longitudinal cohort study of physical exercises in young people.

BACKGROUND: The present study aimed to evaluate the elimination of three common pollutants (dimethoate, benzo(a)pyrene (BaP) and bisphenol A (BPA) by different physical exercises and to assess the possible factors which could affect the pollutants elimination. METHODS: A total of 200 individuals who chose different kinds of exercises in accordance to their own wish were recruited. The levels of urinary pollutants were measured using ß-glucuronidase hydrolysis followed by a high-performance liquid chromatography tandem mass spectrometry-based method. RESULTS: Totally, the levels of dimethoate, BaP and BPA were reduced after physical exercises. However, the elimination of BaP in male was higher than that in female but the elimination of BPA in female was higher than that in male. Multivariate logistic regression showed that the degree of heart rate (HR) change was a protective factor affecting the improvement effect of dimethoate, BaP and BPA while BMI (body mass index) was a risk factor. Nevertheless, sex was a risk factor affecting the improvement of dimethoate and BaP but had a lower efficacy on BPA improvement. CONCLUSION: The present findings indicate that physical exercises can be considered as a novel approach to eliminate pollutants level in human body and can also give suggestions for choosing specific physical exercises to male and female individuals. Moreover, those who are with higher BMI need to lose weight before eliminating pollutant level through physical exercises.

Urinary levels of dimethoate, bisphenol A and benzo[a]pyrene in first-year students of Hohai University from different geographical regions.

BACKGROUND: The objective of this study was to detect the urinary levels of dimethoate, benzo(a) pyrene (BaP), and bisphenol A (BPA) in first-year Hohai University students with different geographic origins. METHODS: First-morning urine samples were collected from 540 healthy freshmen aged 17 to 19 years. Chemical levels were measured using ß-glucuronidase hydrolysis followed by a high-performance liquid chromatography-tandem mass spectrometry-based method. Geometric means (GMs) of these three chemicals are presented by body mass index (BMI) and location in a volume-based and creatinine-standardized way. RESULTS: GM concentrations of omethoate, BPA and 3-OHBaP were 9.47 µg/L (10.80 µg/g creatinine), 3.54 µg/L (4.04 µg/g creatinine) and 0.34 ng/L (0.39 ng/g creatinine), respectively. The GM concentration of omethoate in males was significantly higher than that in females. The individuals with a BMI higher than 23.9 had higher GM concentrations of omethoate, BPA, and 3-OHBaP. The inhabitants of Southwest China had significantly lower GM concentrations of omethoate, BPA, and 3-OHBaP than those who lived in other locations in China. CONCLUSION: The average level of environmental chemical accumulation in freshmen is lower in Southwest China and differs in youth who live in different regions. In addition, obesity is correlated with higher toxin levels in youth.

In situ loading MnO2 onto 3D Aramid nanofiber aerogel as High-Performance lead adsorbent.

Fabricating a high-performance adsorbent as a desirable candidate for removing Pb2+ from aqueous water remains a challenge. Aramid nanofibers (ANFs) are promising building blocks that have realized multifunctional applications due to their intrinsic mechanical and chemical stability. Herein, an in situ loading strategy for preparing nanofiber composite aerogel was proposed by assembling ANFs into a 3D aerogel and applying it as host media for the in situ polymerization of pyrrole followed by facile redox reaction between the polypyrrole (PPy) and MnO4-1 to load manganese dioxide (MnO2). The idea was to fully exploit the structural advantages of ultra-low bulk density, large specific surface area, and high porosity of ANFs, and the possible chemical adsorption characteristics of MnO2 on the basis of ion exchange reaction. The adsorption capacity of 3D ANF/MnO2 composite aerogel was as large as 554.36 mg/g for Pb2+. The adsorption mechanism based on an exchange reaction between Pb2+ and protons on the surface of MnO2 was also investigated. The desorption results showed that the adsorption performance could remain up to 90% after five times of usage. In conclusion, this research provides promising insights into the preparation of high-performance lead adsorbent for water treatment.

A novel prognostic model based on immunogenomics for clear cell renal cell carcinoma.

BACKGROUND: Immune cell infiltration into tumor tissue is closely related to the clinical outcomes of patients with clear cell renal cell carcinoma (ccRCC). This study aimed to screen out potential immune genes associated with ccRCC, analyze their relationships with clinical outcomes, and construct a signature to predict ccRCC. METHODS: The transcriptome RNA-sequencing data in 539 ccRCC and 72 adjacent normal tissues were obtained from TCGA database. Biomedical computational algorithms were conducted to identify immune-related differential expressed genes (IRDGs) and enriched pathways. Then, LASSO Cox and multivariate Cox analyses were performed to screen out genes that were then used to construct the prognostic model. RESULTS: A total of 116 down-regulated and 565 up-regulated IRDGs were identified. Pathway enrichment analysis suggested that IRDGs was mainly enriched in the pathway of "cytokines and cytokine receptors". The entire data of ccRCC were randomly divided into the training set and the test set with a ratio of 1:1. A 4-gene signature was then constructed using LASSO Cox analysis and multivariate Cox analysis in the training set. This prognostic signature could stratify patients into high- and low-risk groups successfully, and serve as an independent predictor when adjusted with clinical factors by univariate and multivariate Cox regression analysis. These results were verified in the test set and the entire set. Besides, the abundance of CD4 + T cells and dendritic cells increased in the high-risk group. Finally, we built a nomogram incorporating risk score and clinical factors to predict the overall survival of ccRCC patients. CONCLUSIONS: These findings may contribute to the research of ccRCC in immunization part.

Risk Factors for Postpartum Stress Urinary Incontinence: a Systematic Review and Meta-analysis.

Stress urinary incontinence (SUI) is a distressing symptom affecting females globally and is one of the most common complications of delivery. The etiology of female SUI is multifactorial, and the trauma caused by delivery is one of the most important risk factors for SUI. We performed a meta-analysis to determine the relationship between these various factors and postpartum SUI. We searched PubMed, Embase, Web of Science, and the Cochrane Library until January 2019 using appropriate keywords and extracted 46 eligible studies that included 73,010 participants. The study protocol was registered with PROSPERO (No. CRD42020150094). The pooled results indicated that 12 risk factors, including vaginal delivery (OR 2.08, 95% CI 1.72-2.52), advanced age at gestation (OR 1.06, 95% CI 1.04-1.08), advanced maternal BMI (OR 1.04, 95% CI 1.03-1.06), excess weight gain during pregnancy (OR 1.13, 95% CI 1.00-1.26), advanced current BMI (OR 1.32, 95% CI 1.02-1.70), diabetes (OR 1.91, 95% CI 1.53-2.38), episiotomy (OR 1.76, 95% CI 1.06-2.94), forceps delivery (OR 2.69, 95% CI 1.25-5.76), gestational UI (OR 5.04, 95% CI 2.07-12.28), gestational SUI (OR 4.28, 95% CI 2.61-7.01), prenatal UI (OR 8.54, 95% CI 3.52-20.70), and early postpartum UI (OR 3.52, 95% CI 1.61-7.69), were associated with postpartum SUI. The findings of this analysis could serve to generate risk prediction models and provide a basis for developing treatment strategies for patients with postpartum SUI.

Resveratrol inhibits the tumor migration and invasion by upregulating TET1 and reducing TIMP2/3 methylation in prostate carcinoma cells.

BACKGROUND: Recently, resveratrol (Res) has been suggested to suppress the migration and invasion of prostate cancer (PCa). In the present study, we aimed to investigate the effects of Res on genomic DNA methylation, as well as the migration and invasion of PCa cells. METHODS: The suppression by Res of the growth of PCa cells was verified through a cytotoxicity assay. In addition, the effects of Res on 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), and ten-eleven translocation 1 (TET1) levels were assessed, and the cell migration and invasion were also determined. The expressions of TET1, tissue inhibitor of metalloproteinases (TIMP) 2, TIMP3, MMP2, and MMP9 were detected through Western blot analysis. Afterward, TET1 was silenced using lentiviral short hairpin RNA to examine the effect of TET1 on the Res-triggered inhibition of migration and invasion of PCa cells. RESULTS: Our results showed that Res upregulated the 5hmC and TET1 levels and downregulated the 5mC level. Moreover, Res also inhibited the migration and invasion of PCa cells, promoted the demethylation of TIMP2 and TIMP3 to upregulate their expressions, and suppressed the expressions of MMP2 and MMP9. The silencing of TET1 in the presence of Res showed that Res could exert its effect through TET1. CONCLUSIONS: Our findings indicated that Res inhibited the migration and invasion of PCa cells via the TET1/TIMP2/TIMP3 pathway, which might potentially serve as a target for the treatment of PCa.

Effects of Patients' Perceptions of Physician-Patient Relational Empathy on an Inflammation Marker in Patients with Crohn's Disease: The Intermediary Roles of Anxiety, Self-Efficacy, and Sleep Quality.

BACKGROUND: Physician-patient empathy is inextricably linked with outcomes of patients. The purpose of this study was to test whether anxiety, self-efficacy, and sleep quality played intermediary roles in relationships between patients' perceptions of physician-patient relational empathy and an inflammation marker in Crohn's disease patients. METHODS: The study included 187 patients. At admission (T1) and 3 months after admission (T2), anxiety, self-efficacy, sleep, and the inflammatory marker IL6 of patients were tested and compared. Patients' perceptions of physician-patient relational empathy (CARE scale) was measured at T2. Correlations among patients' anxiety, self-efficacy, sleep quality, IL6, and CARE scores were explored by Pearson's correlation analysis and a structural equation model. RESULTS: Compared with T1, patients showed higher self-efficacy and sleep quality and lower anxiety and IL6 at T2. Patients' perceptions of physician-patient relational empathy were negatively related to anxiety and IL6 and connected to self-efficacy and sleep quality positively. Patients' anxiety, self-efficacy, and sleep quality played intermediary roles incorrelations between empathy and IL6. CONCLUSION: In correlations of patients' perceptions of physician-patient relational empathy and IL6 in patients with Crohn's disease, patients' anxiety, self-efficacy, and sleep quality acted as intermediary effects. Therefore, medical staff should empathize with patients.

Influence Of Narrative Medicine-Based Health Education Combined With An Online Patient Mutual Assistance Group On The Health Of Patients With Inflammatory Bowel Disease and Arthritis.

BACKGROUND: Inflammatory bowel disease arthritis (IBDA) threatens patients' physical and mental health. Therefore, patients need not only physical therapy, but also adequate health education and psychological support. This study was designed to explore the effect of health education based on narrative medicine combined with an online patient mutual assistance group that was based on the physical and mental health of patients with IBDA. METHODS: A total of 120 patients with IBDA were randomly divided into four groups (30 patients per group). Patients in the control group were given routine health education on the premise of routine treatment. The three treatment groups were given health education based on narrative medicine, online patient mutual assistance group intervention, or combined intervention. Depression, sleep, arthralgia, irritable bowel syndrome (IBS) symptoms, and inflammatory factors were measured and compared before and 1 month after the intervention. RESULTS: Before the intervention, no significant differences were observed in baseline data between the four groups. However, after the intervention, the physical and mental health of patients who received health education based on narrative medicine or online patient mutual assistance groups was improved. Our data showed that patients in the combined intervention group experienced a better outcome. CONCLUSION: Narrative medicine-based health education combined with an online patient mutual assistance group is beneficial to the physical and mental health of IBDA patients. Taken together, this model needs to be further deepened and popularized in clinical practice.