Association between physical activity level and diabetes incidence among Chinese middle-aged and older adults: a cross-sectional study from the China health and retirement longitudinal study.

Background: It has been shown that diabetes is associated with insufficient physical activity among middle-aged and older adults, but the association between different physical activity levels (PAL) and diabetes incidence needs to be further explored. Objective: This study aims to explore the correlation and dose-response relationship between different PAL and the diabetes incidence in middle-aged and older adults. Methods: Utilizing data from the 2018 China Health and Retirement Longitudinal Study (CHARLS), this cross-sectional analysis included 17,226 middle-aged and older adults aged 45 and above. Binary logistic regression models and restricted cubic spline (RCS) were used to explore the correlation and dose-response relationship between different PAL and the incidence of diabetes in the total middle-aged and older adults population as well as in subgroups. Sensitivity analyses were also performed to verify the robustness of the findings. Results: In the entire study population, compared with the lowest PAL, participants in the third and fourth quartiles PAL saw diabetes incidence significantly reduced by 16% (p = 0.005) and 33% (p < 0.001), respectively (p for trend < 0.001). In subgroup analyses, the fourth quartile PAL significantly reduced the diabetes incidence among females, individuals aged 60-69, and rural residents by 25% (p = 0.011), 38% (p < 0.001) and 28% (p < 0.001), respectively. For males, middle-aged (45-59 years), and urban residents, the third quartile PAL reduced diabetes incidence by 22% (p = 0.004), 24% (p = 0.012), 21% (p = 0.013), respectively. When the fourth quartile PAL was reached, the diabetes incidence was significantly reduced in these populations by 41% (p < 0.001), 39% (p < 0.001), and 41% (p < 0.001), respectively. There was a negative dose-response relationship between physical activity and diabetes incidence in specific Chinese middle-aged and older adults population. In addition, sensitivity analyses indicated the robustness of the findings. Conclusion: Higher PAL was associated with lower diabetes incidence in specific Chinese middle-aged and older adults population. It is feasible to use physical activity to predict diabetes incidence in this demographic, and high PAL may be an effective means of preventing and controlling diabetes.

METTL3 mediated ferroptosis in chondrocytes and promoted pain in KOA via HMGB1 m6A modification.

Methyltransferase-like 3 (METTL3) plays a role in the development of knee osteoarthritis (KOA). However, the mechanism underlying the role of METTL3 in KOA is unclear. This work investigated the effects of MELLT3 on ferroptosis and pain relief in in vitro and in vivo KOA models. Chondrocytes were treated with 10 ng/mL interleukin-1ß (IL-1ß) or 5 µM Erastin (ferroptosis inducer). IL-1ß or Erastin treatment inhibited cell viability and glutathione levels; increased Fe2+, lipid reactive oxygen species and malondialdehyde production; and decreased glutathione peroxidase 4, ferritin light chain and solute carrier family 7 member 11 levels. The overexpression of METTL3 facilitated the N6-methyladenosine methylation of high mobility group box 1 (HMGB1). HMGB1 overexpression reversed the effect of sh-METTL3 on IL-1ß-treated chondrocytes. A KOA rat model was established by the injection of monosodium iodoacetate into the joints and successful model establishment was confirmed by haematoxylin and eosin staining and Safranin O/Fast Green staining. METTL3 depletion alleviated cartilage damage, the inflammatory response, ferroptosis and knee pain in KOA model rats, and these effects were reversed by the addition of HMGB1. In conclusion, METTL3 depletion inhibited ferroptosis and the inflammatory response, and ameliorated cartilage damage and knee pain during KOA progression by regulating HMGB1.

The effectiveness of extended reality on relieving pain after total knee arthroplasty: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Patients with total knee arthroplasty (TKA) often suffer from severe postoperative pain, which seriously hinders postoperative rehabilitation. Extended reality (XR), including virtual reality, augmented reality, and mixed reality, has been increasingly used to relieve pain after TKA. The purpose of this study was to evaluate the effectiveness of XR on relieving pain after TKA. METHODS: The electronic databases including PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and clinicaltrials.gov were searched for studies from inception to July 20, 2023. The outcomes were pain score, anxiety score, and physiological parameters related to pain. Meta-analysis was performed using the Review Manager 5.4 software. RESULTS: Overall, 11 randomized control trials (RCTs) with 887 patients were included. The pooled results showed XR had lower pain scores (SMD = - 0.31, 95% CI [- 0.46 to - 0.16], P < 0.0001) and anxiety scores (MD = - 3.95, 95% CI [- 7.76 to - 0.13], P = 0.04) than conventional methods. The subgroup analysis revealed XR had lower pain scores within 2 weeks postoperatively (SMD = - 0.49, 95% CI [- 0.76 to - 0.22], P = 0.0004) and XR had lower pain scores when applying XR combined with conventional methods (SMD = - 0.43, 95% CI [- 0.65 to - 0.20], P = 0.0002). CONCLUSION: This systematic review and meta-analysis found applying XR could significantly reduce postoperative pain and anxiety after TKA. When XR was combined with conventional methods, postoperative pain can be effectively relieved, especially within 2 weeks after the operation. XR is an effective non-pharmacological analgesia scheme.

Targeting TAOK1 with resveratrol inhibits esophageal squamous cell carcinoma growth in vitro and in vivo.

The worldwide incidence and mortality rates of esophageal squamous cell carcinoma (ESCC) have increased over the last decade. Moreover, molecular targets that may benefit the therapeutics of patients with ESCC have not been fully characterized. Our study discovered that thousand and one amino-acid protein kinase 1 (TAOK1) is highly expressed in ESCC tumor tissues and cell lines. Knock-down of TAOK1 suppresses ESCC cell proliferation in vitro and patient-derived xenograft or cell-derived xenograft tumors growth in vivo. Moreover, TAOK1 overexpression promotes ESCC growth in vitro and in vivo. Additionally, we identified that the natural small molecular compound resveratrol binds to TAOK1 directly and diminishes the kinase activity of TAOK1. Targeting TAOK1 directly with resveratrol significantly inhibits cell proliferation, induces cell cycle arrest and apoptosis, and suppresses tumor growth in ESCC. Furthermore, the silencing of TAOK1 or the application of resveratrol attenuated the activation of TAOK1 downstream signaling effectors. Interestingly, combining resveratrol with paclitaxel, cisplatin, or 5-fluorouracil synergistically enhanced their therapeutic effects against ESCC. In conclusion, this work illustrates the underlying oncogenic function of TAOK1 and provides a theoretical basis for the application of targeting TAOK1 therapy to the clinical treatment of ESCC.

The mechanism of lncRNA SNHG1 in osteogenic differentiation via miR-497-5p/ HIF1AN axis.

The pivotal role of lncRNAs in osteoporosis progression and development necessitates a comprehensive exploration of the functional and precise molecular mechanisms underlying lncRNA SNHG1's regulation of osteoblast differentiation and calcification. The study involved inducing BMSCs cells to differentiate into osteoblasts, followed by transfections of miR-497-5p inhibitors, pcDNA3.1-SNHG1, sh-HIF1AN, miR-497-5p mimics, and respective negative controls into BMSCs. Quantitative PCR (qPCR) was employed to assess the expression of SNHG1 and miR-497-5p. Western Blotting was conducted to measure the levels of short stature-related transcription factor 2 (RUNX2), osteopontin (OPN), osteocalcin (OCN), and HIF1AN. Alkaline phosphatase (ALP) activity was determined using appropriate assay kits. Calcium nodule staining was performed through Alizarin red staining. Dual luciferase reporter gene assays were executed to validate the interaction between SNHG1 and miR-497-5p, as well as HIF1AN. Throughout osteogenic differentiation, there was a down-regulation of SNHG1 and HIF1AN, in contrast to an elevation in miR-497-5p levels. Direct interactions between miR-497-5p and both SNHG1 and HIF1AN were observed. Notably, SNHG1 exhibited the ability to modulate HIF1AN by influencing miR-497-5p, thereby inhibiting osteogenic differentiation. Functioning as a competitive endogenous RNA, lncRNA SNHG1 exerts an inhibitory influence on osteogenic differentiation via the miR-497-5p/HIF1AN axis. This highlights the potential for lncRNA SNHG1 to emerge as a promising therapeutic target for osteoporosis. The study's findings pave the way for a novel target strategy in the future treatment of osteoporosis.

Long Non-coding RNA SNHG1 Suppresses the Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells by Binding with HMGB1.

Osteoporosis (OP) has a significant detrimental impact on the health of the elder. Long-term clinical effectiveness of current drugs used for OP treatment is limited. Therefore, it is very important to explore novel treatment targets for OP. The expression of SNHG1, HMGB1, OCN and OPN in gene level was measured using RT-qPCR, and the protein expression was determined by Western blotting assay. The concentration of IL-1ß and IL-18 in supernatant of the bone marrow mesenchymal stem cells (BMSCs) was measured by ELISA. The interaction between SNHG1 and HMGB1 was confirmed by RNA pull down. Besides, alizarin red staining was performed to evaluate the differentiation of BMSCs into osteoblast. SNHG1 and HMGB1 were found to be upregulated in the serum of OP patients. During the osteogenic differentiation of BMSCs, the expression of osteoblastogenesis markers (OCN and OPN) and the activity of ALP were upregulated, while the expression levels of SNHG1 and HMGB1 were decreased in a time-dependent manner. In addition, the interaction between SNHG1 and HMGB1, expression of pyroptosis-associated factors (caspase-1 p20 and GSDMD-N), and secretion of IL-1ß and IL-18 were also decreased during osteogenic differentiation. Interestingly, increasing SNHG1 promoted HMGB1 expression, activated pyroptosis, but inhibited osteogenic differentiation. Silencing HMGB1 or inhibiting caspase-1 partially rescued the inhibitory effect of SNHG1 on osteogenic differentiation. Our findings indicate that SNHG1 suppresses the osteogenic differentiation of BMSCs by activating pyroptosis through interaction with HMGB1 and promotion of HMGB1 expression. Our work provides further evidence supporting SNHG1 acts as a potential target for OP treatment, and reveals for the first time that SNHG1 regulates osteogenic differentiation by affecting pyroptosis.

Augmented reality-assisted versus conventional total hip arthroplasty: a systematic review and meta-analysis.

BACKGROUND: Extended reality (XR), including virtual reality, augmented reality (AR), and mixed reality, has been used to help achieve accurate acetabular cup placement in total hip arthroplasty (THA). This study aimed to compare the differences between XR-assisted and conventional THA. METHODS: In this systematic review and meta-analysis, electronic databases including PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and clinicaltrials.gov were searched for studies from inception to September 10, 2023. The outcomes were accuracy of inclination and anteversion, duration of surgery, and intraoperative blood loss. Meta-analysis was performed using Review Manager 5.4 software. RESULTS: A total of five studies with 396 patients were included in our study. The pooled results indicated AR-assisted THA had better accuracy of inclination and anteversion than conventional THA (SMD = - 0.51, 95% CI [- 0.96 to - 0.07], P = 0.02; SMD = - 0.96, 95% CI [- 1.19 to - 0.72], P < 0.00001), but duration of surgery and intraoperative blood loss were similar in the two groups. CONCLUSION: This systematic review and meta-analysis found that AR-assisted THA had better accuracy of inclination and anteversion than conventional THA, but the duration of surgery and intraoperative blood loss were similar in the two groups. Based on the pooled results, we suggested that AR can provide more precise acetabular cup placement than conventional methods in THA.

HECW2 promotes the progression and chemoresistance of colorectal cancer via AKT/mTOR signaling activation by mediating the ubiquitin-proteasome degradation of lamin B1.

Colorectal cancer (CRC) is among the most common malignancies worldwide. Although a recent study has shown that E3 ubiquitin ligases play a major role in regulating the occurrence and development of CRC, there are few reports on the role of the E3 ubiquitin ligase HECW2(HECT, C2 and WW domain containing E3 ubiquitin protein ligase 2) in CRC progression and chemoresistance. We found that HECW2 is highly expressed in CRC tissues. HECW2 knockdown inhibits CRC progression and chemoresistance, whereas HECW2 overexpression has the opposite effect. Mechanistically, HECW2 activates the AKT/mTOR signaling pathway by mediating the ubiquitin-proteasome degradation of lamin B1, thereby promoting CRC progression and chemoresistance. Our findings suggest that HECW2 may be a promising novel therapeutic target for CRC treatment.

Pathophysiological Insight into Fatty Acid-Binding Protein-4: Multifaced Roles in Reproduction, Pregnancy, and Offspring Health.

Fatty acid-binding protein-4 (FABP4), commonly known as adipocyte-fatty acid-binding protein (A-FABP), is a pleiotropic adipokine that broadly affects immunity and metabolism. It has been increasingly recognized that FABP4 dysfunction is associated with various metabolic syndromes, including obesity, diabetes, cardiovascular diseases, and metabolic inflammation. However, its explicit roles within the context of women's reproduction and pregnancy remain to be investigated. In this review, we collate recent studies probing the influence of FABP4 on female reproduction, pregnancy, and even fetal health. Elevated circulating FABP4 levels have been found to correlate with impaired reproductive function in women, such as polycystic ovary syndrome and endometriosis. Throughout pregnancy, FABP4 affects maternal-fetal interface homeostasis by affecting both glycolipid metabolism and immune tolerance, leading to adverse pregnancy outcomes, including miscarriage, gestational obesity, gestational diabetes, and preeclampsia. Moreover, maternal FABP4 levels exhibit a substantial linkage with the metabolic health of offspring. Herein, we discuss the emerging significance and potential application of FABP4 in reproduction and pregnancy health and delve into its underlying mechanism at molecular levels.

Effects of Aerobic Exercise on Serum Adiponectin Concentrations in Children and Adolescents with Obesity: A Systematic Review and Meta-Analysis.

Serum adiponectin plays a vital role in various physiological processes, such as anti-inflammatory, anti-atherosclerotic, anti-apoptotic and pro-angiogenic activities. Any abnormalities in its concentration can lead to adverse health outcomes, particularly in children and adolescents. Therefore, it is crucial to investigate factors influencing serum adiponectin concentrations in this population. The primary objective of this study was to systematically evaluate the impact of aerobic exercise on serum adiponectin concentrations in children and adolescents with obesity. To achieve this, a comprehensive literature search was conducted up to January 2023, utilising five databases: PubMed, Web of Science, Embase, Cochrane Library and Clinicaltrial.gov. The inclusion criteria involved studies that focused solely on aerobic exercise as an intervention for children and adolescents with obesity. Only studies that reported outcome indicators related to serum adiponectin were considered for analysis. The quality of the included studies was assessed using the Cochrane Risk of Bias (ROB) assessment tool, and statistical analysis was performed using RevMan 5.4.1 analysis software. This meta-analysis incorporated data from eight trials, involving a total of 272 subjects. The results demonstrated that aerobic training significantly increased serum adiponectin concentrations [standardized mean difference (SMD) = 0.85; 95% confidence interval (CI) = 0.33 to 1.37; I2 = 0%; p = 0.001] in children and adolescents with obesity when compared to non-exercise controls. Furthermore, the magnitude of this effect appears to be influenced by the intensity of aerobic exercise, with higher-intensity aerobic exercise resulting in greater increases in serum adiponectin concentrations.

Knockdown of NF-κB activating protein promotes pancreatic cancer growth and metastasis through mTOR signaling pathway.

BACKGROUND: NF-κB activating protein (NKAP) acts as a transcriptional suppressor in the Notch signaling pathway, It plays a role in hematopoiesis maintenance, immune cell development, maturation, and functional competency acquisition. NKAP has been found to act as an oncogene in many tumors, but it has not been reported in PAAD.The purpose of this study was to investigate the effect of NKAP on the growth and metastasis of pancreatic adenocarcinoma(PAAD). METHODS AND RESULTS: In this study, western blot and qRT-PCR showed that highly expressed NKAP was found in PAAD cell lines, and small interfering RNA (siRNA) was employed to reduce the expression of NKAP in PAAD cell lines. The results of CCK-8, clony formation, Transwell and flow cytometry showed that knockdown of NKAP significantly inhibited biological function of PAAD cells, and increased cell apoptosis. Study also observed that knockdown of NKAP inhibited the expression levels of apoptosis proteins and cyclin in PAAD cells. In addition, mTOR's degree of phosphorylation and the expression of its downstream target p70S6K can both be activated by NKAP. This effect was also confirmed in salvage experiments performed with Rapamycin(RaPa), an inhibitor of mTOR. At the end of the experiment, It was investigated how NKAP affected the drug sensitivity of gemcitabine used to treat PAAD. The results showed that knocking down NKAP could increase the drug sensitivity of gemcitabine. CONCLUSIONS: NKAP as an oncogene regulates the development of PAAD cells. The research found that the mTOR signaling pathway is engaged in the oncogenic role of NKAP in PAAD for the first time.

Early surgery within 48 h was associated with reduced perioperative blood loss and red blood cell transfusion requirements in older patients with hip fracture: a retrospective study.

PURPOSE: The aim of this study was to analyze the relationship between the timing of surgery and perioperative blood loss, red blood cell (RBC) transfusion rate, and RBC transfusion volume in older patients with hip fracture. METHODS: From January 2020 to August 2022, this retrospective study enrolled older patients with hip fracture who underwent surgery in our hospital. The demographics, fracture type, type of surgery, time from injury to hospital, timing of surgery, medical history (hypertension, diabetes), duration of surgery, intraoperative blood loss, laboratory tests, and preoperative, postoperative and perioperative RBC transfusion requirements were recorded and analyzed. According to the surgical treatment within 48 h or after 48 h after admission, the patients were divided into early surgery group (ES) and delayed surgery group (DS). RESULTS: A total of 243 older patients with hip fracture were finally included in the study. Among these, 96 patients (39.51%) underwent surgery within 48 h of admission and 147 (60.49%) underwent surgery after this time. Total blood loss (TBL) in the ES group was lower than that in the DS group (576.03 ± 265.57 ml vs 699.26 ± 380.58 ml, P = 0.003). Preoperative RBC transfusion rate, and preoperative and perioperative RBC transfusion volume in the ES group were significantly lower than those in the DS group (15.63% vs 26.53%, P = 0.046; 50.00 ± 128.15 ml vs 117.01 ± 225.85 ml, P = 0.004; 80.21 ± 196.63 ml vs 144.90 ± 253.52 ml, P = 0.027). CONCLUSION: Timing of surgery within 48 h of admission for older patients with hip fracture was associated with reduced the total blood loss and RBC transfusion requirements during the perioperative period.

Inhibition of STAT3 signaling as critical molecular event in HUC-MSCs suppressed Glioblastoma Cells.

Objective: We investigated the effect of human umbilical cord mesenchymal stem cells (HUC-MSCs) supernatants on proliferation, migration, invasion, and apoptosis in glioblastoma (GBM) cell lines RG-2, U251, U87-MG, and LN-428, as well as their apoptosis and autophagy-mediated through IL-6/JAK2/STAT3 signaling pathway to explore the molecular mechanisms. Methods: In this study, RG-2, U251, U87-MG, and LN-428 cells were treated with 9 mg/ml HUC-MSCs supernatants. Their responses to HUC-MSCs supernatants treatment and the status of STAT3 signaling were analyzed by multiple experimental approaches to elucidate the importance of HUC-MSCs supernatants for GBM. Results: The results demonstrated that after treatment with HUC-MSCs supernatants, in vitro proliferation of RG-2, U251, U87-MG, and LN-428 cells were inhibited, and their sustained growth was also blocked. RG-2, U251, and U87-MG cells showed significant S phase accumulation, while LN-428 cells were blocked in G0/G1 phase. Their migratory invasive capacities were inhibited, and their apoptosis and autophagy ratios were increased. These effects were mediated through the IL-6/JAK2/STAT3 and its downstream signaling pathway. Conclusion: Our data showed that HUC-MSCs supernatants had anti-tumor effects on GBM cells. It inhibited the proliferation, migration, and invasion of GBM cells and promoted their apoptosis. Negative regulation of the IL-6/JAK2/STAT3 signaling pathway enhanced apoptosis and autophagy in tumor cells, thereby improving the therapeutic effect on GBM.

DNA-Programmed Tuning of the Growth and Enzyme-Like Activity of a Bimetallic Nanozyme and Its Biosensing Applications.

Nanozymes, which combine the merits of both nanomaterials and natural enzymes, have aroused tremendous attention as new representatives of artificial enzyme mimics. However, it still remains to be a great challenge to rationally engineer the morphologies and surface properties of nanostructures that lead to the desired enzyme-like activities. Here, we report a DNA-programming seed-growth strategy to mediate the growth of platinum nanoparticles (PtNPs) on gold bipyramids (AuBPs) for the synthesis of a bimetallic nanozyme. We find that the preparation of a bimetallic nanozyme is in a sequence-dependent manner, and the encoding of a polyT sequence allows the successful formation of bimetallic nanohybrids with greatly enhanced peroxidase-like activity. We further observe that the morphologies and optical properties of T15-mediated Au/Pt nanostructures (Au/T15/Pt) change over the reaction time, and the nanozymatic activity can be tuned by controlling the experimental conditions. As a concept application, Au/T15/Pt nanozymes are used to establish a simple, sensitive, and selective colorimetric assay for the determination of ascorbic acid (AA), alkaline phosphatase (ALP), and the inhibitor sodium vanadate (Na3VO4), demonstrating excellent analytical performance. This work provides a new avenue for the rational design of bimetallic nanozymes for biosensing applications.

RPL11 promotes non-small cell lung cancer cell proliferation by regulating endoplasmic reticulum stress and cell autophagy.

BACKGROUND: Abnormal biogenesis and ribosome free function of ribosomal proteins (RPs) is important for tumorgenesis and development. Ribosomal protein L11 (RPL11) is a component of ribosomal 60 S large subunit with different roles in different cancers. Here, we aimed to unravel the role of RPL11 in non-small cell lung cancer (NSCLC), especially those affecting cell proliferation. METHODS: RPL11 expression in NCI-H1650, NCI-H1299, A549 and HCC827 and normal lung bronchial epithelial cells HBE was detected using western blotting. The function of RPL11 in NSCLC cells were determined by investigating cell viablity, colony formation and cell migration. Mechanism expoloration of RPL11 effect on NSCLC cells proliferation was explored using flow cytometry, and the effect on autophagy was investigated by the additon of autophagy inhibitor chloroquine (CQ) and endoplasmic reticulum stress (ERS) inhibitor tauroursodeoxycholic acid (TUDCA). RESULTS: RPL11 was highly expressed in NSCLC cells. Extopic expression of RPL11 promoted NCI-H1299 and A549 cells proliferation, and migration, and promoted the transition from the G1 phase to the S phase of the cell cycle. Small RNA interference of RPL11 (siRNA) suppressed NCI-H1299 and A549 cells proliferation and migration and arrested the cell cycle in G0/G1 phase. Moreover, RPL11 promoted NSCLC cell proliferation by modulating autophagy and ERS. Expression levels of autophagy and ERS markers were induced by RPL11 overexpression and inhibited by siRPL11. CQ partially suppressed RPL11-induced A549 and NCI-H1299 proliferation: CQ addition reduced RPL11-induced cells viability and clone numbers and reversed the cell cycle process. ERS inhibitor (TUDCA) partially reversed RPL11-induced autophagy. CONCLUSION: Taken together, RPL11 has a tumor-promoting role in NSCLC. It promotes the cell proliferation of NSCLC cells by regulating ERS and autophagy.

hMSC exosomes as a novel treatment for female sensitive skin: An in vivo study.

Background: Recent studies have reported that the incidence of sensitive skin is increasing. Skin sensitivity and skin barrier functions were related to many skin diseases including atopic dermatitis, psoriasis, rosacea, and so on. Mesenchymal stem cell (MSC)-derived exosomes (hMSC) might be considered as a new effective therapeutic scheme. Aims: This study aims to investigate the safety and efficacy of hMSC exosomes as a novel topical treatment for sensitive skin. Patients/Methods: Exosomes were extracted from primary hMSC via ultracentrifugation method. The morphology of hMSC exosomes was studied via transmission electron microscope. Expression of exosome specific surface marker was detected via Western blot. 22 subjects (female, aged 18-55) diagnosed with sensitive skin were enrolled. Follow-up was conducted before, 7-day, 14-day, and 28-day after hMSC exosomes use. Transepidermal water loss (TEWL), surface hydration, sebum secretion, and L*a*b* value were simultaneously tested at the same time point in an environment-controlled room. Results: Under transmission electron microscopy, the extracted hMSC exosomes were circular or elliptical with intact membrane structure, and their diameters ranged mainly from 40 to 80 nm. Western blot showed that the expression of markers CD63, CD9, and Tsg101 was positive. Brownian motion based nanoparticle trajectory analysis (NTA) showed that the main peak of particle size distribution occurred around 96 nm, the average particle size was 122 nm, and the main peak accounted for 96.7%. All this conformed to the biological characteristics of exosomes standardized by the International Society for Extracellular Vesicles. In the clinical trial, scores of objective symptoms including roughness, scales, erythema, and subjective symptoms including tension, burning, or itching, were improved after 7-, 14-, and 28- day using hMSC-exosomes. TEWL, hydration, sebum, pH, and a* values were tended to return to the level of healthy skin. Conclusion: The hMSC-exosomes, with the advantages of biocompatibility and biodegradability, could improve clinical symptoms and eruptions in sensitive skin patients, and might be as an MSC cell-free novel therapy in sensitive skin-related disease treatment.

Bioinformatics analysis of prognostic value and immunological role of MeCP2 in pan-cancer.

Methyl-CpG-binding protein 2(MeCP2) is an important epigenetic regulatory factor that promotes many tumor developments, such as liver cancer, breast cancer, and colorectal cancer. So far, no pan-cancer analysis has been reported. Therefore, this study aims to explore pan-cancer's prognostic value, immune infiltration pattern, and biological function. We used bioinformatics methods to analyze the expression and prognostic significance of MeCP2, and the relationship between MeCP2 and clinicopathological parameters, genetic variation, methylation, phosphorylation, immune cell infiltration, and biological function in pan-cancer from using a public database. The results showed that expression of MeCP2 was up-regulated in 8 cancers and down-regulated in 2 cancers, which was remarkably correlated with the prognosis, pathological stage, grade and subtype of cancers. The promoter methylation level of MeCP2 DNA was decreased in bladder urothelial carcinoma (BLCA), breast invasive carcinoma (BRCA), liver hepatocellular carcinoma (LIHC), prostate adenocarcinoma (PRAD), uterine corpus endometrial carcinoma (UCEC), testicular germ cell tumors (TGCT), and stomach adenocarcinoma (STAD);decreased phosphorylation of S25, S90, S92, S241, S286, S325 and S435 was found in MeCP2, such as UCEC, lung adenocarcinoma (LUAD), ovarian serous cystadenocarcinoma (OV), colon adenocarcinoma (COAD), and kidney renal clear cell carcinoma (KIRC). Furthermore, MeCP2 expression was significantly associated with multiple immunomodulators and immune cell infiltration levels across most tumors. Therefore, our pan-cancer explored the prognostic markers and immunotherapeutic value of MeCP2 in different cancers.

The alteration from agricultural to nomadic regimes resulted in human livelihood transformation in North-Central China during the 12th century: The archaeobotanical evidence.

Human livelihoods provided a crucial economic foundation for social development in ancient times and were influenced by various factors including environmental change, agricultural origin and intensification, as well as long-distance exchange and culinary tradition. The effect of geopolitical change on human subsistence, especially the shifts between agricultural and nomadic regimes, has not been well understood due to the absence of detailed historical records and archaeological evidence. During the 12th century, the control of the Zhengding area in Hebei Province of north-central China changed from the Northern Song (960-1127 CE) to the Jurchen Jin Dynasty (Jin Dynasty; 1115-1234 CE). Recent excavation of the Zhengding Kaiyuan Temple South (ZKS) site in the area provides a rare opportunity to study human livelihood transformation in relation to geopolitical change. In total, 21,588 charred crop caryopses including foxtail millet, wheat, broomcorn millet, hulled barley, and rice, and other carbonized remains including 55.15 g of boiled foxtail millet and 353.5 g of foxtail millet caryopses were identified, and nine AMS 14C dates of crop remains were obtained from the Northern Song and Jin layers at the ZKS site. This revealed that the dominant plant subsistence transformed from wheat to foxtail millet during the change from the Northern Song to the Jin Dynasties in Zhengding area. By comparing with historical documents and paleoclimate records, we propose that this abnormal shift of primary staple food from the relatively high-yield wheat to low-yield foxtail millet was induced by the traditional dietary preference for foxtail millet in the nomadic Jin society. The Jin government levied foxtail millet as taxation and promoted massive immigration from northeastern China to north-central China to consolidate their rule, which resulted in the adoption of foxtail millet as the most important crop in Zhengding area. The advantage for the cultivation of this frost-sensitive crop in north-central China over northeast China was probably enhanced by notable cold events during the 12th century, while the primary influencing factor for the transformation of human livelihoods in north-central China during that period was geopolitics rather than climate change.

CTRP3 alleviates myocardial ischemia/reperfusion injury in mice through activating LAMP1/JIP2/JNK pathway.

Myocardial ischemia reperfusion (I/R) injury is an important complication of myocardial infarction reperfusion therapy, and no effective treatment has been identified. Based on preexisting evidence, C1q/tumor necrosis factor-related protein 3 (CTRP3) has been reported to be closely associated with myocardial dysfunction. In this study, we found that CTRP3 was downregulated in acute coronary syndrome (ACS) patients and myocardial I/R mice. Silence of CTRP3 aggravated cardiac systolic function due to I/R of mice, while CTRP3 overexpression ameliorated cardiac function. Moreover, overexpression of CTRP3 improved I/R inhibitory effects on the levels of creatinine phosphokinase (CPK), lactate dehydrogenase (LDH) and cardiac troponin-I (cTn-I), myocardial infarction area, the intensity of the 3-nitrotyrosine (3-NT), apoptosis and protein levels of LAMP1, JNK-Interacting Protein-2 (JIP-2) and JNK, while these effects could be exacerbated by downregulation of CTRP3. Co-IP experiments could identify physical interactions between CTRP3 and lysosomal-associated membrane protein 1 (LAMP1) and Numb and JIP2. LAMP1 silence aggravated the inhibition effects of I/R on JIP2 and JNK protein expression, CPK, LDH and cTn-I levels and caspase-3 activity, while overexpression of LAMP1 recovered these inhibition effects of I/R. JNK inhibitor (SP600125) could reverse the inhibitory effects of CTRP3 overexpression on CPK, LDH, cTn-I, myocardial infarction, strong positive staining for 3-NT and apoptosis. These findings demonstrated that CTRP3 protected against injury caused by myocardial I/R through activating LAMP1/JIP2/JNK pathway to attenuate myocardial injury, improve left ventricular function, decrease myocardial infarction, and reduce myocardial apoptosis.

LINC01588 regulates WWP2-mediated cardiomyocyte injury by interacting with HNRNPL.

Cardiomyocyte dysfunction and apoptosis induced by ischemia-hypoxia are common features of many acute and chronic heart diseases. WW domain-containing E3 ubiquitin ligase (WWP2) has been identified as an important regulator in pathogenesis of some health-threatening diseases. Although a couple of recent reports prompted the potential role of WWP2 in heart dysfunction, however, its exact role and how its expression was regulated in ischemic-hypoxic cardiomyocytes are still elusive. Here, we found that WWP2 protein level was induced in anoxia/reoxygenation (A/R) treated cardiomyocytes in a time-dependent manner, accompanied by synchronous expression of LINC01588 and HNRNPL. Knockdown of LINC01588 increased cardiomyocyte apoptosis, the level of oxidative stress, and expression of pro-inflammatory cytokine genes, down-regulated the expression of WWP2 and promoted expression of SEPT4 gene that contributed to cardiomyocyte dysfunction and was a target gene of WWP2. LINC01588 overexpression improved the functions of A/R treated cardiomyocytes, up-regulated WWP2 and reduced SEPT4 expression. In the mechanism exploration, we found that LINC01588 could directly bind with HNRNPL protein that could interact with WWP2, suggesting that WWP2 was involved in the regulation of LINC01588 in A/R treated cardiomyocytes. Moreover, WWP2 inhibition declined the protective role of LINC01588 in cardiomyocyte dysfunction induced by A/R. Finally, we demonstrated that LINC01588 overexpression improved acute myocardial infarction in mice in vivo. In conclusion, LINC01588 improved A/R-induced cardiomyocyte dysfunction by interacting with HNRNPL and promoting WWP2-mediated degradation of SEPT4.