Exosomal microRNA-363 mediates the destructive effect of M1 macrophages on chondrocytes by repressing G3BP2.

M1 polarization of synovial macrophages contributes to cartilage degeneration and osteoarthritis (OA) development. However, limited knowledge is available about how M1 macrophages affect the biological properties of chondrocytes. This study aimed to explore the role of exosomal microRNAs (miRs) released from M1 macrophages in modulating the proliferation and survival of chondrocytes. Through bioinformatic analysis and experimental validation, we indicated that miR-363 was selectively induced in M1 macrophages (CD68+CD80+) but not M2 macrophages (CD68+CD206+). The upregulation of miR-363 in M1 macrophages depended on the activation of STAT1 signaling. Clinically, OA patients had a significantly higher miR-363 level in synovial fluid than control individuals without OA. Functional studies revealed that inhibition of miR-363 blocked the M1 macrophage polarization induced by lipopolysaccharide and IFN-γ. Moreover, exosomal miR-363 released from M1 macrophages significantly suppressed the proliferation and survival and induced inflammatory gene expression in chondrocytes. G3BP2 was identified as a target gene for miR-363 and could be negatively regulated by miR-363. Knockdown of G3BP2 recapitulated the effect of miR-363 overexpression on chondrocytes. Most importantly, enforced expression of G3BP2 attenuated miR-363-induced apoptosis and inflammatory response in chondrocytes. In conclusion, miR-363 plays an indispensable role in M1 macrophage polarization and can be released from M1 macrophages via exosomes to cause chondrocyte injury and inflammation. The miR-363/G3BP2 axis may represent a promising target for the prevention of OA development.

MTFR2 accelerates hepatocellular carcinoma mediated by metabolic reprogramming via the Akt signaling pathway.

Metabolic reprogramming has recently been identified as a hallmark of malignancies. The shift from oxidative phosphorylation to glycolysis in hepatocellular carcinoma (HCC) meets the demands of rapid cell growth and provides a microenvironment for tumor progression. This study sought to uncover the function and mechanism of MTFR2 in the metabolic reprogramming of HCC. Elevated MTFR2 expression was associated with poor patient prognosis. Downregulation of MTFR2 blocked malignant behaviors, epithelial-to-mesenchymal transition (EMT), and glycolysis in HCC cells. Nuclear transcription factor Y subunit gamma (NFYC) was also associated with poor patient prognosis, and NFYC bound to the promoter of MTFR2 to activate transcription and promote Akt signaling. The repressive effects of NFYC knockdown on EMT and glycolysis in HCC cells were compromised by MTFR2 overexpression, elicited through the activation of the Akt signaling. Knockdown of NFYC slowed the growth and intrahepatic metastasis in vivo, which was reversed by MTFR2 overexpression. In conclusion, our work shows that activation of MTFR2 by the transcription factor NFYC promotes Akt signaling, thereby potentiating metabolic reprogramming in HCC development. Targeting the NFYC/MTFR2/Akt axis may represent a therapeutic strategy for HCC.

The causal role of circulating inflammatory markers in osteoporosis: a bidirectional Mendelian randomized study.

Background: Osteoporosis (OP) associated with aging exerts substantial clinical and fiscal strains on societal structures. An increasing number of research studies have suggested a bidirectional relationship between circulating inflammatory markers (CIMs) and OP. However, observational studies are susceptible to perturbations in confounding variables. In contrast, Mendelian randomization (MR) offers a robust methodological framework to circumvent such confounders, facilitating a more accurate assessment of causality. Our study aimed to evaluate the causal relationships between CIMs and OP, identifying new approaches and strategies for the prevention, diagnosis and treatment of OP. Methods: We analyzed publicly available GWAS summary statistics to investigate the causal relationships between CIMs and OP. Causal estimates were calculated via a systematic analytical framework, including bidirectional MR analysis and Bayesian colocalization analysis. Results: Genetically determined levels of CXCL11 (OR = 0.91, 95% CI = 0.85-0.98, P = 0.008, PFDR = 0.119), IL-18 (OR = 0.88, 95% CI = 0.83-0.94, P = 8.66×10-5, PFDR = 0.008), and LIF (OR = 0.86, 95% CI = 0.76-0.96, P = 0.008, PFDR = 0.119) were linked to a reduced risk of OP. Conversely, higher levels of ARTN (OR = 1.11, 95% CI = 1.02-1.20, P = 0.012, PFDR = 0.119) and IFNG (OR = 1.16, 95% CI = 1.03-1.30, P = 0.013, PFDR = 0.119) were associated with an increased risk of OP. Bayesian colocalization analysis revealed no evidence of shared causal variants. Conclusion: Despite finding no overall association between CIMs and OP, five CIMs demonstrated a potentially significant association with OP. These findings could pave the way for future mechanistic studies aimed at discovering new treatments for this disease. Additionally, we are the first to suggest a unidirectional causal relationship between ARTN and OP. This novel insight introduces new avenues for research into diagnostic and therapeutic strategies for OP.

SETBP1 activation upon MDM4-enhanced ubiquitination of NR3C1 triggers dissemination of colorectal cancer cells.

Colorectal cancer (CRC) presents a growing concern globally, marked by its escalating incidence and mortality rates, thus imposing a substantial health burden. This investigation delves into the role of nuclear receptor subfamily 3 group C member 1 (NR3C1) in CRC metastasis and explores the associated mechanism. Through a comprehensive bioinformatics analysis, NR3C1 emerged as a gene with diminished expression levels in CRC. This finding was corroborated by observations of a low-expression pattern of NR3C1 in both CRC tissues and cells. Furthermore, experiments involving NR3C1 knockdown revealed an exacerbation of proliferation, migration, and invasion of CRC cells in vitro. Subsequent assessments in mouse xenograft tumor models, established by injecting human HCT116 cells either through the tail vein or at the cecum termini, demonstrated a reduction in tumor metastasis to the lung and liver, respectively, upon NR3C1 knockdown. Functionally, NR3C1 (glucocorticoid receptor) suppressed SET binding protein 1 (SETBP1) transcription by binding to its promoter region. Notably, mouse double minute 4 (MDM4) was identified as an upstream regulator of NR3C1, orchestrating its downregulation via ubiquitination-dependent proteasomal degradation. Further investigations unveiled that SETBP1 knockdown suppressed migration and invasion, and epithelial to mesenchymal transition of CRC cells, consequently impeding in vivo metastasis in murine models. Conversely, upregulation of MDM4 exacerbated the metastatic phenotype of CRC cells, a propensity mitigated upon additional upregulation of NR3C1. In summary, this study elucidates a cascade wherein MDM4-mediated ubiquitination of NR3C1 enables the transcriptional activation of SETBP1, thereby propelling the dissemination of CRC cells.

Detection value of third-generation sequencing to identify the pathogenic organisms in prosthetic joint infection.

To compare the detection value of third-generation sequencing (TGS) with pathogenic microbial culture in prosthetic joint infection (PJI). Arthrocentesis was performed on 29 patients who underwent hip and knee revision surgeries. In the PJI group, TGS detected 85.71 % of positive cases, while pathogenic microbial culture detected only 42.85 %. TGS identified 17 different pathogenic microorganisms, including Staphylococcus epidermidis, Staphylococcus aureus, Streptococcus lactis, and Mycobacterium tuberculosis complex. In the loosening group, TGS was positive in one patient, while microbial culture was negative in all cases. TGS showed higher sensitivity (85.71 % vs. 42.85 %), comparable specificity (93.33 % vs. 100 %), and similar positive predictive value (92.31 % vs. 100 %) compared to culture.However, TGS had a higher negative predictive value (87.5 % vs. 65.22 %).Additionally, TGS provided faster results (mean time 23.8±3.6 h) compared to microbial culture (mean time 108.0±9.4 h).These findings suggest that TGS holds promise for detecting pathogenic microorganisms in PJI and has potential for clinical application.

Cancer-Related Fatigue and Its Influencing Factors Among Colorectal Cancer Patients: A Generalized Linear Modeling Approach.

Purpose: This study aimed to improve cancer-related fatigue (CRF) and health outcomes of colorectal cancer patients by understanding the status quo of CRF, exploring the relations of coping, anxiety symptoms, depressive symptoms, body image perception and CRF, and also identifying the factors affecting CRF based on a generalized linear modeling approach. Patients and Methods: An exploratory cross-sectional study was conducted on 370 colorectal cancer patients at two hospitals in Anhui Province, China, from July 2020 to February 2021. The data were collected by using general information questionnaire, cancer fatigue scale, simplified coping style questionnaire, generalized anxiety disorder-7 scale, patient health questionnaire-9, and body image scale. Descriptive statistics, t-tests, one-way analysis of variance, Pearson correlation analyses, and generalized linear model analyses were applied to analyze the data. Results: The average CRF score of the patients was 21.612 (SD=6.160), with a prevalence rate of 69.4% for clinically relevant fatigue. The generalized linear model revealed that: In step 1, gender (female) (B=1.799, Waldχ2=7.506, p=0.006), per capita monthly income (1001-3000 RMB) (B=-1.673, Waldχ2=5.536, p=0.019) and treatment modalities (chemotherapy+others) (B=2.425, Waldχ2=8.211, p=0.004) were related to CRF. In step 2, depressive symptoms (B=1.223, Waldχ2=129.019, p<0.001) and negative coping strategies (B=0.215, Waldχ2=11.347, p=0.001) exhibited significant positive correlations with CRF, positive coping strategies (B=-0.319, Waldχ2=59.175, p<0.001) showed significant negative correlations with CRF; While anxiety symptoms (B=0.162, Waldχ2=1.840, p=0.175) and body image perception (B=0.013, Waldχ2=0.048, p=0.826) had no correlations with CRF. Conclusion: The prevalence of CRF was relatively high among colorectal cancer patients. Coping and depressive symptoms were the modifiable influencing factors of CRF. Tailored interventions dedicated to promoting positive coping behavior, diminishing negative coping behavior and reducing depressive symptoms may improve the CRF of patients with colorectal cancer. Healthcare providers working with these patients should receive corresponding education and training in these complementary treatments. Additionally, when developing non-pharmacological interventions, appropriate consideration of the patients' gender, income condition and the type of anticancer treatment is also necessary.

LncRNA RUNX1-IT1 is downregulated in gastric cancer and suppresses the maturation of miR-20a by binding to its precursor.

BACKGROUND: RUNX1-IT1 has been characterized as a tumor suppressive long non-coding RNA (lncRNA) in several types of cancer but not gastric cancer (GC). This study aimed to explore the role of RUNX1-IT1 in GC. METHODS: The expression of RUNX1-IT1, microRNA (miR)-20a precursor and mature miR-20a in GC and healthy tissues donated by GC patients (n=62) were measured by RT-qPCR. Correlation analysis was performed by linear regression. The expression of mature miR-20a and miR-20a precursor in cells with overexpression of RUNX1-IT1 was also determined by RT-qPCR. Cell invasion and migration were evaluated by Transwell assays. RESULTS: RUNX1-IT1 was downregulated in GC. Across GC tissues, RUNX1-IT1 and mature miR-20a were inversely correlated. However, RUNX1-IT1 and miR-20a precursor were not closely correlated. RUNX1-IT1 and miR-20a precursor were predicted to interact with each other, and overexpression of RUNX1-IT1 in GC cells decreased the expression levels of mature miR-20a. Transwell assay showed that the enhancing effect of miR-20a on cell invasion and migration was reduced by overexpression of RUNX1-IT1. CONCLUSIONS: RUNX1-IT1 may suppress the GC cell movement by inhibiting the maturation of miR-20a.

Association Between Fatigue and Falls Risk Among the Elderly Aged Over 75 Years in China: The Chain Mediating Role of Falls Efficacy and Lower Limb Function.

Background: Although fatigue has been shown to be strongly associated with falls risk, very few studies have focused on its mechanism involved in community-dwelling older subjects. The purpose of this study was to explore the relationship between fatigue and falls risk and its internal mechanism by constructing a chain mediation model. Methods: A cross-sectional study design was adopted. A convenience sample of 270 older adults was recruited from July to October 2021 in an urban community, in Beijing, China. The participants completed the 14-item Fatigue Scale (FS-14), Falls Efficacy Scale International (FES-I), the Short Physical Performance Battery (SPPB) and Fall-Risk Self-Assessment Questionnaire (FRQ) to measure fatigue, falls efficacy, lower limb function and falls risk. The theory of unpleasant symptoms was used as a conceptual framework. Structural equation modeling (SEM) was utilized to test the hypothetical model. Results: The overall fit of final model was found to be satisfactory: χ2/df = 1.61, CFI = 0.971, TLI = 0.962, RMSEA = 0.049 (95% CI 0.030/0.066) and SRMR = 0.023. Fatigue had a direct effect on falls risk (ß = 0.559, S.E. = 0.089, 95% CI 0.380/0.731), and it also had indirect effects on falls risk (ß = 0.303, S.E. = 0.072, 95% CI 0.173/0.460) through mediating factors. Falls efficacy and lower limb function were the main mediating variables, and there was a chain mediating effect (ß = 0.015, S.E. = 0.010, 95% CI 0.003/0.046). Conclusions: Our study suggests that fatigue can influence falls risk among the elderly in China. There are many mediating paths between fatigue and falls risk. These results may help healthcare professionals to better understand the inherent relationship between fatigue and fall risk that may benefit older adults.

Activating transcription factor 2 promotes the progression of hepatocellular carcinoma by inducing the activation of the WHSC1-mediated TOP2A/PI3K/AKT axis.

Activating transcription factor 2 (ATF2) is a tumor driver gene implicated in several human malignancies. This study aimed to determine the roles of ATF2 and its related molecules in the tumorigenesis of hepatocellular carcinoma (HCC). According to the Pan-cancer bioinformatics system, ATF2 is highly expressed in HCC. An increase in the expression of ATF2 was identified in clinically collected tumor tissues and procured HCC cells. The silencing of ATF2 reduced the viability, colony formation, invasion, and death resistance of HepG2 and SNU-398 cells in vitro. ATF2 promoted the transcription of Wolf-Hirschhorn syndrome candidate 1 (WHSC1) by binding to its promoter. WHSC1 further increased the expression of DNA topoisomerase II alpha (TOP2A) in HCC by inducing the dimethylation of histone H3 lysine 36 (H3K36me2) in the TOP2A promoter region. TOP2A activated the oncogenic PI3K/AKT signaling pathway. Further overexpression of WHSC1 activated the TOP2A/PI3K/AKT axis and restored the malignant behaviors of HCC cells suppressed by ATF2 silencing in vitro. In summary, this study demonstrated that, depending on WHSC1, ATF2 can activate the TOP2A/PI3K/AKT signaling cascade to promote the tumorigenesis of HCC. ATF2, WHSC1, and TOP2A may serve as potential targets in managing HCC.

Increasing global urban exposure to flooding: An analysis of long-term annual dynamics.

An improved understanding of global Urban Exposure to Flooding (UEF) is essential for developing risk-reduction strategies for sustainable urban development. This study is the first to assess the long-term historical global UEF at a fine spatial resolution (i.e., 30 m) and annual temporal frequency, with consideration of smaller urban areas in the exposure assessment compared to those using coarse resolution data. We assessed the UEF by investigating the spatially explicit urban expansion in the 100-year floodplain extents. The global UEF increased more than four-fold from 16,443 km2 in 1985 to 92,233 km2 in 2018 with accelerated temporal trends. The most notable growth in UEF occurred in Asia (74.1%), followed by Europe (11.6%), Northern America (8.7%), Africa (2.9%), Southern America (2.2%), and Australia (0.5%). Notably, China and US were the two countries with the largest UEF, accounting for about 61.5% of global growth in UEF. In addition, only 1.2% of global floodplains were occupied by urban expansion by 2018, whereas this percentage reached 20% in the basins of Western Europe, Eastern Asia, and Northeastern US. Moreover, although the floodplains only accounted for 5.5% of the global land areas, 12.6% of the urban expansion occurred in the floodplains from 1985 to 2018, with the most rapid increases in the basins in Southeastern and Eastern China. Our findings highlight that the trends of accelerated increasing urban exposure to flooding have been occurring for at least the past three decades.

Effects of psychosocial factors on posttraumatic growth among lung cancer patients: A structural equation model analysis.

OBJECTIVE: The purpose of this study was to investigate how locus of control, coping strategies, emotion regulation strategies and social support affect posttraumatic growth. METHODS: A cross-sectional study design was adopted. A convenience sample of 540 patients with lung cancer was recruited from November 2016 to July 2017 at two tertiary grade A hospitals in China. The participants completed a series of questionnaires. Structural equation modelling was used to explore the effects of psychosocial factors on posttraumatic growth. RESULTS: Social support had a direct positive effect on posttraumatic growth (ß = 0.318, SE = 0.071, BC 95% CI = 0.252/0.390), and it also had indirect effects on posttraumatic growth (ß = 0.112, SE = 0.023, BC 95%CI = 0.088/0.135) through mediating psychological factors. Coping strategies and the cognitive reappraisal emotion regulation strategy were the main mediating variables, explaining approximately 73.1% of the indirect effect between social support and posttraumatic growth. CONCLUSIONS: Our study suggests that Chinese lung cancer survivors can show relatively high posttraumatic growth. There are many mediating paths between social support and posttraumatic growth. These results may help healthcare professionals to identify the psychosocial factors that may benefit lung cancer patients and develop interventions to promote posttraumatic growth.

Incidence and risk factors related to fear of falling during the first mobilisation after total knee arthroplasty among older patients with knee osteoarthritis: A cross-sectional study.

BACKGROUND: The factors that lead to the fear of falling among older people after total knee arthroplasty (TKA) are poorly understood. The present study aims to examine the fear of falling among such patients and to determine the factors that are associated with that fear. METHODS: A total of 285 patients aged ≥65 with knee osteoarthritis who underwent TKA at an orthopaedic hospital between November 2019 and May 2020 completed surveys about their own first mobilisation after TKA. They were asked to indicate whether they were afraid of falling by asking a single question, and what their pain level was on a visual analogue scale. They also completed the General Anxiety Disorder scale, the Geriatric Depression Scale-Short Form and the Social Support Rating Scale. Multivariate logistic regression was used to identify risk factors for fear of falling during the first mobilisation after TKA. This study was reported in compliance with the STROBE checklist for cross-sectional studies (see Supplementary File S1). RESULTS: Just over half (56.5%) of participants reported being afraid of falling. Multivariate logistic regression identified three independent risk factors that explained a total of 31% of the variance in the fear of falling: female sex (odds ratio (OR) = 4.21, 95% confidence interval (CI) = 2.35-7.55), higher body mass index (OR =3.93, 95% CI =1.53-10.10) and higher anxiety (OR = 1.56, 95% CI = 1.37-1.78). CONCLUSIONS: Many older patients fear falling when they begin to move after TKA, particularly women and those with higher body mass index or anxiety. These subgroups may merit special attention from healthcare professionals to mitigate their fears and optimise recovery after TKA.

Factors associated with the resilience of Tibetan adolescent survivors five years after the 2010 Yushu earthquake.

Resilience contributes to the recovery of disaster victims. The resilience of Tibetan adolescents after the Yushu earthquake has not been properly studied. This study aimed to examine the current resilience and associated factors in Tibetan adolescent survivors in the hardest-hit area 5 years after the Yushu earthquake. This cross-sectional survey was conducted in the area hit the hardest by the Yushu earthquake. Data were collected from 4681 respondents in October and November 2015. Measurements included the participant characteristics, traumatic earthquake experience, the Connor-Davidson resilience scale (CD-RISC), and the social support appraisals (SS-A) scale. The individual datasets were randomized as 80% for the training set and 20% for the validation set. The mean resilience score of the Tibetan adolescent survivors was 55.0±12.3. Thirteen variables were entered into the regression equation. The three dimensions of social support (from family, from friends, from others than family/friends) were positively associated with resilience (all P<0.05), among which support from others than family/friends was the strongest (r = 0.388, P<0.001). Academic performance, activeness of participation in school activities, harmonious relationship with teachers/classmates, health over the last year, and regular physical exercise were positively associated with resilience (all P<0.05). Being female and being extremely worried about their own lives were negatively associated with resilience (both P<0.05). In conclusion, among Tibetan adolescent survivors to the Yushu earthquake of 2010, support from others than family/friends was the strongest positive factor associated with resilience, while being female and extreme worry about their own lives were negative factors. These results expand our knowledge regarding resilience in Tibetan adolescent disaster survivors.

Accumulation of microplastics in typical commercial aquatic species: A case study at a productive aquaculture site in China.

The widespread occurrence of microplastics in the marine environment has drawn global attention because microplastics may impact the populations of marine organisms. As such, aquaculture industry may suffer from microplastic pollution, especially when plastic products are widely used for aquaculture. Here, we assessed the abundance and characteristics (type, size and composition) of microplastics in sediment and typical commercial species (fish, bivalves and shrimps) in an aquaculture site at Xiangshan Bay, which has been operated intensively for decades. Satellite remote sensing images revealed that aquaculture activities were associated with microplastic pollution in sediment, where the microplastics (51-88 items/kg dry weight) were mostly fibres (>94%) and between 500 and 2000 µm. Cellulose was the predominant polymer (60-88% of microplastic composition), followed by polypropylene. Microplastics accumulated in all the commercial species (0.95-2.1 items per individual), where shrimp (Parapenaeopsis hardwickii) had lower potential for microplastic accumulation than the other species. The predominance of fibres and cellulose in the commercial species implies their limited ability to recognize the type and composition of microplastics during ingestion. Given the limited accumulation of microplastics in these typical commercial species even at a productive aquaculture site, we suggest that microplastics may not increase the health risk of consuming seafood and their impacts on commercial species may be less deleterious than previously thought.

Patient delay and associated factors among Chinese women with breast cancer: A cross-sectional study.

To examine the current situation of patient delay and to identify factors associated with patient delay among women with breast cancer in China.A total of 283 women, aged 23 to 83 years old and with histologically confirmed breast cancer, were investigated in this cross-sectional study. The women were recruited from seven selected hospitals in Sichuan Province, China. Face-to-face interviews using a structured questionnaire were performed.Among the 283 participants, the range of patient delay was 0.2 to 900 days with a median patient delay of 50 days. A total of 35.8% of patients waited ≥90 days to access medical treatment after symptom onset. Binary logistic regression analysis showed that the main predictors of patient delay were knowledge of breast cancer symptoms (OR = 0.716, 95%CI:0.637-0.804, P = .000), external health locus of control (OR = 1.173, 95%CI:1.087-1.266, P = .000), breast self-examination/physical examination (OR = 0.065, 95%CI: 0.007-0.590, P = .015), perceived health competence (OR = 0.873, 95%CI:0.808-0.944, P = .000), family support (OR = 0.911,95%CI:0.847-0.981, P = .013), pain stimulation (OR = 0.191, 95%CI:0.046-0.792, P = .023) and age (OR = 1.028, 95%CI:1.000-1.058, P = .049).These factors explained 41.0% of the variance.Information on the current situation and predictors of patient delay in Chinese women with breast cancer might provide meaning insights into the early diagnosis of breast cancer. The results of this study may help health professionals develop specific clinical practice strategies to reduce patient delay of initial treatment as a way to improve outcomes for women with breast cancer.

On Optimal Imaging Angles in Multi-Angle Ocean Sun Glitter Remote-Sensing Platforms to Observe Sea Surface Roughness.

Sea surface roughness (SSR) is a key physical parameter in studies of air-sea interactions and the ocean dynamics process. The SSR quantitative inversion model based on multi-angle sun glitter (SG) images has been proposed recently, which will significantly promote SSR observations through multi-angle remote-sensing platforms. However, due to the sensitivity of the sensor view angle (SVA) to SG, it is necessary to determine the optimal imaging angle and their combinations. In this study, considering the design optimization of imaging geometry for multi-angle remote-sensing platforms, we have developed an error transfer simulation model based on the multi-angle SG remote-sensing radiation transmission and SSR estimation models. We simulate SSR estimation errors at different imaging geometry combinations to evaluate the optimal observation geometry combination. The results show that increased SSR inversion accuracy can be obtained with SVA combinations of 0° and 20° for nadir- and backward-looking SVA compared with current combinations of 0° and 27.6°. We found that SSR inversion prediction error using the proposed model and actual SSR inversion error from field buoy data are correlated. These results can provide support for the design optimization of imaging geometry for multi-angle ocean remote-sensing platforms.