Cost-effective fabrication of a high-conductivity copper electrode for heterojunction solar cells via laser-induced selective metallization.

Replacing expensive silver with inexpensive copper for the metallization of silicon wafer solar cells can lead to significant reductions in material costs associated with cell production, but the susceptibility of the Cu material to oxidation remains a challenging issue to solve. In this study, we investigate copper metallization of Indium Tin Oxide surfaces to define copper grid electrodes for heterojunction cells. We propose a novel laser-induced selective metallization (LISM) method to fabricate large-scale copper electrodes for heterojunction solar cells at low cost. This study includes a comprehensive evaluation of the morphological characteristics and electrical properties of the electrodes. The effects of laser parameters on the morphology, composition, size, and conductivity of copper electrodes are investigated. The goal of establishing the process window is to obtain the optimal laser parameters for manufacturing highly conductive copper electrodes. These optimized parameters will then be employed to fabricate high-performance electrodes for solar cells. Furthermore, a detailed analysis of the mechanism underlying laser selective metallization is provided. The resulting Cu electrodes exhibit high conductivity and low resistivity of 1.98 × 10-5Ω.cm, demonstrating the potential of this method for efficient and cost-effective solar electrode production.

Prognostic Implications of LRP1B and Its Relationship with the Tumor-Infiltrating Immune Cells in Gastric Cancer.

BACKGROUND: Recent studies have shown that low-density lipoprotein receptor-related protein 1b (LRP1B), as a potential tumor suppressor, is implicated in the response to immunotherapy. The frequency of LRP1B mutation gene is high in many cancers, but its role in gastric cancer (GC) has not been determined. METHODS: The prognostic value of LRP1B mutation in a cohort containing 100 patients having received radical gastrectomy for stage II-III GC was explored. By analyzing the data of LRP1B mRNA, the risk score of differentially expressed genes (DEGs) between LRP1B mutation-type and wild-type was constructed based on the TCGA-STAD cohort. The infiltration of tumor immune cells was evaluated by the CYBERSORT algorithm and verified by immunohistochemistry. RESULTS: LRP1B gene mutation was an independent risk factor for disease-free survival (DFS) in GC patients (HR = 2.57, 95% CI: 1.28-5.14, p = 0.008). The Kaplan-Meier curve demonstrated a shorter survival time in high-risk patients stratified according to risk score (p < 0.0001). CYBERSORT analysis showed that the DEGs were mainly concentrated in CD4+ T cells and macrophages. TIMER analysis suggested that LRP1B expression was associated with the infiltration of CD4+ T cells and macrophages. Immunohistochemistry demonstrated that LRP1B was expressed in the tumor cells (TCs) and immune cells in 16/89 and 26/89 of the cohort, respectively. LRP1B-positive TCs were associated with higher levels of CD4+ T cells, CD8+ T cells, and CD86/CD163 (p < 0.05). Multivariate analysis showed that LRP1B-positive TCs represented an independent protective factor of DFS in GC patients (HR = 0.43, 95% CI: 0.10-0.93, p = 0.042). CONCLUSIONS: LRP1B has a high prognostic value in GC. LRP1B may stimulate tumor immune cell infiltration to provide GC patients with survival benefits.

Modified Stabilization Test to Diagnose Chronic Syndesmotic Injuries Based on Posture Control.

BACKGROUND: To propose and validate a modified noninvasive method for the diagnosis of chronic syndesmotic injuries. METHODS: This study included 16 patients with chronic ankle instability. Herein, we propose the Modified Stabilization Test, a new measurement for use in the diagnosis of chronic syndesmotic injury, as determined by wearing a 60-kPa pneumatic brace. The test combines the center of pressure and sensory organization test to measure postural control. For comparison, we also measured the tibiofibular clear space, tibiofibular overlap, and medial clear space using anteroposterior radiograph; a line marked horizontally above the tibial plaque using computed tomography (CT) to measure the syndesmotic gap and fibular rotation angle; and magnetic resonance imaging (MRI) scans to determine the presence of the λ sign. The distance of syndesmosis was confirmed in 16 individuals through arthroscopy, and the results of the examination were used to determine the diagnostic efficacy of each index. RESULTS: Receiver operating characteristic curve analysis revealed that the optimal cut-off value, sensitivity, and specificity of the Modified Stabilization Test for the diagnosis of chronic syndesmotic injuries were 0.80, 100%, and 87.5%, respectively. The area under the curve (AUC) of the Modified Stabilization Test was 0.906 (95% CI 0.656, 0.993; P < .001), which was superior to imaging indices such as radiography, CT, and MRI (AUC = 0.516-0.891). CONCLUSION: We developed the Modified Stabilization Test-a noninvasive diagnostic tool for the screening of chronic syndesmotic injuries. The test showed high sensitivity and specificity for the identification of chronic syndesmotic injuries and is helpful in the identification of chronic syndesmotic injuries. LEVEL OF EVIDENCE: Level II, diagnostic-investigating a diagnostic test.

Sufficient Phosphorus Enhances Resistance and Changes Accumulation of Lead in Chlamydomonas reinhardtii.

Phosphorus (P) is critical for algal growth and resistance to environmental stress. However, little is known about the effects of P supply on the lead (Pb) toxicity and accumulation in microalgae. We set up two P concentrations, 315 (PL ) and 3150 µg L-1 (PH ), in algal culture, and the responses of Chlamydomonas reinhardtii to various Pb treatments (0, 200, 500, 1000, 2000, and 5000 µg L-1 ) were investigated. Compared with the PL condition, PH promoted cell growth but reduced cellular respiration by approximately 50%. Moreover, PH alleviated damage to the photosynthetic system in algal cells after Pb stress. After exposure to 200-2000 µg L-1 Pb, higher Pb2+ concentrations and Pb removal were observed in the PL medium. However, under exposure to 5000 µg L-1 Pb, less Pb2+ was present but more Pb was removed by the algal cells in the PH medium. More P supply enhanced the secretion of extracellular fluorescent substances by C. reinhardtii. Transcriptomic analysis showed that genes associated with synthesis of phospholipids, tyrosine-like proteins, ferredoxin, and RuBisCO were up-regulated after Pb exposure. Together the findings of our study demonstrated the critical roles of P in Pb accumulation and resistance in C. reinhardtii. Environ Toxicol Chem 2023;42:1960-1970. © 2023 SETAC.

Microplastics perturb colonic epithelial homeostasis associated with intestinal overproliferation, exacerbating the severity of colitis.

A great amount of the population died due to living or working in an unhealthy environment, highlighting the critical role of environmental pollutants in inducing diseases. Microplastics are widespread environmental pollutants and have been found in various tissues of human beings, yet the risk of microplastics in the occurrence of disease, especially environmentally-related colitis, is unclear. This study focused on the effects of microplastics exposure on intestinal homeostasis and the initiation of colitis. We noticed that microplastics exposure had a limited impact on mice, as verified by no difference observed in bodyweight change, IL-1ß and IL-6 levels in jejunum and liver. Nevertheless, in the colon, the IL-1ß and IL-6 levels were slightly increased and the goblet cell number was decreased. Interestingly, we observed that crypt number and depth, the levels of intestinal stem cell markers, combined with the expression of proliferating cell nuclear antigen and proto-oncogene c-Myc were all significantly increased with microplastics treatment, indicating the overproliferation of colonic mucosa. The effect of microplastics on proliferation and differentiation of crypt was further demonstrated to be regulated by the overactivation of the Notch signaling pathway in intestinal organoids. Furthermore, microplastics exposure accelerated the development of colitis with severe bodyweight loss, diarrhea and bloody stools, macroscopic and pathological damage, and inflammation levels. Worsened liver pathological damage and inflammation in mice with colitis under microplastics exposure also were found. These results suggested that microplastics disrupted the balance between colonic epithelium self-renewal and differentiation, exacerbating the colitis, and might be an environmental-related disease risk factor.

Experimental Static and Dynamic Characteristics of Recycled Waste Tire Rubber Particle-Cement-Sand Composite Soil.

To investigate the static and dynamic characteristics of rubber-sand composite soil (RS soil) reinforced with cement, a series of triaxial compression tests and resonant column tests was performed by considering the influence of rubber content (10%, 20%, 30%, 40%, and 50%), cement content (0, 1.5, 2.5, 3.5 and 4.0 g/100 mL), and effective consolidation confining pressure (50, 100, and 150 kPa). Compared with the RS soil, the addition of cement significantly improved the shear strength of a cement-rubber-sand composite soil (RCS soil), based on an undrained shear test. The increase in cement content not only makes the elastic modulus and cohesion of the RCS soil increase but also reduces the internal friction angle of the RCS soil. With the increase in rubber content, the failure of the RCS soil samples changes from strain-softening to hardening, and the prediction equation of the initial elastic modulus of the RCS soil is given herein when the recommended cement content is 3.5 g/100 mL. The effects of rubber content, cement content, and effective confining pressure on the dynamic shear modulus and damping ratio of the RCS soil were studied via the resonant column test. The test results show that the increase in rubber content slows down the modulus attenuation of the RCS soil, but increases its damping ratio. The test results also show that the increase in cement content makes the bonding force between particles greater so that the modulus attenuation of the RCS soil becomes slower and the damping ratio is reduced. At the same time, according to the change rule of the maximum dynamic shear modulus of the RCS soil with the rubber content, when the recommended cement content is 3.5 g/100 mL, an empirical formula and recommended value of the shear modulus Gmax of the RCS soil are proposed.

Indispensable role of melatonin, a scavenger of reactive oxygen species (ROS), in the protective effect of Akkermansia muciniphila in cadmium-induced intestinal mucosal damage.

The gastrointestinal tract is the main target of cadmium toxicity. However, whether Akkermansia muciniphila (A. muciniphila), which has been reported to be the next generation of promising probiotics, can alleviate cadmium-induced intestinal damage has not been investigated. In this study, we found that compared to the cadmium exposure group, mice gavaged with A. muciniphila showed less severe intestinal mucosal damage, with improved bodyweight, colon length, a decline in inflammation, and significantly increased glutathione and goblet cell numbers. Meanwhile, melatonin was interestingly found to be strikingly increased after A. muciniphila treatment. We then demonstrated that melatonin also could ameliorate the intestinal mucosal damage caused by cadmium through scavenging reactive oxygen species (ROS) and increasing the number of goblet cells. Furthermore, mice treated with inhibitors had a low level of melatonin and could not reproduce the beneficial effects of the A. muciniphila. Our results implied that the regulation of melatonin production by A. muciniphila is associated with an increase in enterochromaffin cells number, which determine melatonin secretion. This study indicated that the A. muciniphila-melatonin axis reduces cadmium-induced damage by increasing the goblet cells and scavenging the ROS, which may guide the prevention of the toxic effects of heavy metals.

Total Talar Replacement With Custom-Made Vitallium Prosthesis for Talar Avascular Necrosis.

Background: The current study investigated the application of three-dimensional (3D) printing technology in the treatment of talar avascular necrosis (TAN). Custom-made Vitallium talar prostheses were designed and generated via 3D printing. We hypothesized that these talar prostheses would facilitate more stable positioning, better ergonomically fit the ankle joint surfaces, and promote favorable long-term prognoses. Material and Methods: Computed tomography scans of both ankle joints were acquired from three patients diagnosed with TAN. The talar on the unaffected side was used as the design blueprint. Hence, with the aid of 3D printing technology a customized talar prosthesis made from a novel Vitallium alloy could be manufactured for each individual patient. Results: In all three cases there were no signs of prosthesis loosening or substantial degenerative change in the surrounding area of the joint, but small osteophytes were observed on the tibial side and navicular side. No chronic infection or other prosthesis-related complications were observed in any of the patients. All three were able to walk without pain at the most recent follow-up. Conclusion: With the aid of 3D printing and a novel Vitallium alloy, total talar replacement achieved encouraging results in 3/3 patients. All patients were satisfied with their joint function, and were able to return to their daily activities without limitations. Although more cases and longer-term follow-up periods are required, the success rate reported herein is encouraging.

Effects of traditional Chinese medicine collaborative model (TCMCM) combined with adjuvant chemotherapy on IIIb and IIIc gastric cancer: a protocol for a randomized controlled trial.

BACKGROUND: Metastasis and/or recurrence can decrease the survival time of gastric cancer patients undergoing radical operation. Among them, those with stage IIIb and IIIc are especially at a high risk of metastasis and recurrence. The traditional Chinese medicine collaborative model (TCMCM) has been used in the treatment of cancer; however, its effects have not been systematically evaluated. This study is designed to evaluate whether TCMCM can decrease adverse effects after chemotherapy and reduce the recurrence and metastasis of stage IIIb and IIIc gastric cancer. METHODS/DESIGN: This prospective, multicenter, randomized, open-label trial will recruit 260 patients with stage IIIb and IIIc gastric cancer who undergo radical surgery for D2 lymphadenectomy. The patients will be randomly assigned to receive usual adjuvant chemotherapy and TCMCM (intervention group) in a 1:1 ratio. Patients in the intervention group will receive an oral traditional Chinese formula, auricular acupressure, and acupoint therapy. All participants will receive usual adjuvant chemotherapy. The primary outcome is a 3-year disease-free survival rate. Secondary outcomes include quality of life, side effects caused by chemotherapy, and safety-related measures. Assessments will be performed during the screening period, at 4 and 8 cycles after adjuvant chemotherapy, and 9, 12, 18, 24, 30, and 36 months after randomization. Adverse events will be recorded. In addition, biological samples will be collected for mechanism analysis. DISCUSSION: This will be the first clinical trial to evaluate the effects of TCMCM on disease-free survival (DFS) and quality of life in patients with stage IIIb and IIIc gastric cancer. Our results may be used to standardize TCMCM. We will also perform a larger-scale clinical trial in the future. TRIAL REGISTRATION: ClinicalTrials.gov NCT03607656 . Registered on 1 July 2018. The final protocol version is V1.1.

Acacetin inhibits invasion, migration and TGF-ß1-induced EMT of gastric cancer cells through the PI3K/Akt/Snail pathway.

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is a pivotal cellular phenomenon involved in tumour metastasis and progression. In gastric cancer (GC), EMT is the main reason for recurrence and metastasis in postoperative patients. Acacetin exhibits various biological activities. However, the inhibitory effect of acacetin on EMT in GC is still unknown. Herein, we explored the possible mechanism of acacetin on EMT in GC in vitro and in vivo. METHODS: In vitro, MKN45 and MGC803 cells were treated with acacetin, after which cell viability was detected by CCK-8 assays, cell migration and invasion were detected by using Transwell and wound healing assays, and protein expression was analysed by western blots and immunofluorescence staining. In vivo, a peritoneal metastasis model of MKN45 GC cells was used to investigate the effects of acacetin. RESULTS: Acacetin inhibited the proliferation, invasion and migration of MKN45 and MGC803 human GC cells by regulating the expression of EMT-related proteins. In TGF-ß1-induced EMT models, acacetin reversed the morphological changes from epithelial to mesenchymal cells, and invasion and migration were limited by regulating EMT. In addition, acacetin suppressed the activation of PI3K/Akt signalling and decreased the phosphorylation levels of TGF-ß1-treated GC cells. The in vivo experiments demonstrated that acacetin delayed the development of peritoneal metastasis of GC in nude mice. Liver metastasis was restricted by altering the expression of EMT-related proteins. CONCLUSION: Our study showed that the invasion, metastasis and TGF-ß1-induced EMT of GC are inhibited by acacetin, and the mechanism may involve the suppression of the PI3K/Akt/Snail signalling pathway. Therefore, acacetin is a potential therapeutic reagent for the treatment of GC patients with recurrence and metastasis.

Electron microscopic imaging and NanoSIMS investigation on physiological responses of Aspergillus niger under Pb(II) and Cd(II) stress.

In the bioremediation process, coexistence of lead (Pb) and cadmium causes complex toxicity, resulting in the difficulty of bioremediation. This study investigated the physiological responses and bioaccumulation mechanisms of the typical filamentous fungus Aspergillus niger under the coexistence of Pb and Cd. Four treatments were set up, i.e., control, sole Pb, sole Cd, and coexistence of Pb and Cd. The morphology of A. niger were observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM), respectively. Then, nano-scale secondary ion mass spectrometry (NanoSIMS) was applied to accurately investigate the distribution of heavy metals in the fungal cells under the coexistence of Pb and Cd. Finally, the metallogenic process and mineral types were simulated by Geochemist's Workbench (GWB). The electron microscopic and NanoSIMS imaging showed that Pb and Cd were accumulated in both the extracellular and intracellular regions of the A. niger cells. In particular, the accumulated Pb content was ten times higher than that of Cd. However, Cd showed stronger toxicity than Pb to A. niger. Compared with the control treatment, Cd stress resulted in a two-fold increase of cell diameter and more extracellular substances, whereas the cell diameter increased nearly four times in the coexistence treatment. Moreover, the bioaccumulation of Pb was more intense than that of Cd during competitive sorption. The GWB simulation confirmed that Pb2+ can form multiple minerals (e.g., PbC2O4, PbHPO4, and Pb3(PO4)2, etc.), which significantly weakened its toxicity on the cell surface. This study elucidated the morphological characteristics of A. niger and competitive bioaccumulation under the coexistence of Pb and Cd, which would facilitate the application of microorganisms to the bioremediation of coexisted metals.

TP53 mutation and MET amplification in circulating tumor DNA analysis predict disease progression in patients with advanced gastric cancer.

BACKGROUND: Gastric cancer (GC) is a heterogeneous disease that encompasses various molecular subtypes. The molecular mutation characteristics of circulating tumor DNA (ctDNA) in advanced gastric cancer (AGC), especially the clinical utility of TP53 mutation and MET amplification in ctDNA need to be further explored. OBJECTIVES: The aim of this study was mainly to assess the clinical utility of TP53 mutation and MET amplification in ctDNA as biomarkers for monitoring disease progression of AGC. PATIENTS AND METHODS: We used multigene NGS-panel technology to study the characteristics of ctDNA gene mutations and screen the key mutant genes in AGC patients. The Kaplan-Meier method was used to calculate the survival probability and log-rank test was used to compare the survival curves of TP53 mutation and MET amplification in ctDNA of AGC patients. The survival time was set from the blood test time to the follow-up time to observe the relationship between the monitoring index and tumor prognosis. RESULTS: We performed mutation detection on ctDNA in 23 patients with AGC and identified the top 20 mutant genes. The five most frequently mutated genes were TP53 (55%), EGFR (20%), ERBB2 (20%), MET (15%) and APC (10%). TP53 was the most common mutated gene (55%) and MET had a higher frequency of mutations (15%) in our study. Kaplan-Meier analysis showed that patients with TP53 mutant in ctDNA had shorter overall survival (OS) than these with TP53 wild (P < 0.001). The Allele frequency (AF) of TP53 mutations in patient number 1 was higher in the second time (0.94%) than in the first time (0.36%); the AF of TP53 mutations in patient number 16 was from scratch (0∼0.26%). In addition, the AF of TP53 mutations in patients who survive was relatively low (P = 0.047). Simultaneously, Kaplan-Meier analysis showed that patients with MET amplification also had shorter OS than these with MET without amplification (P < 0.001). CONCLUSION: TP53 and MET are the two common frequently mutant genes in ctDNA of AGC patients.TP53 mutation and MET amplification in ctDNA could predict disease progression of AGC patients.

Timer-based proteomic profiling of the ubiquitin-proteasome system reveals a substrate receptor of the GID ubiquitin ligase.

Selective protein degradation by the ubiquitin-proteasome system (UPS) is involved in all cellular processes. However, the substrates and specificity of most UPS components are not well understood. Here we systematically characterized the UPS in Saccharomyces cerevisiae. Using fluorescent timers, we determined how loss of individual UPS components affects yeast proteome turnover, detecting phenotypes for 76% of E2, E3, and deubiquitinating enzymes. We exploit this dataset to gain insights into N-degron pathways, which target proteins carrying N-terminal degradation signals. We implicate Ubr1, an E3 of the Arg/N-degron pathway, in targeting mitochondrial proteins processed by the mitochondrial inner membrane protease. Moreover, we identify Ylr149c/Gid11 as a substrate receptor of the glucose-induced degradation-deficient (GID) complex, an E3 of the Pro/N-degron pathway. Our results suggest that Gid11 recognizes proteins with N-terminal threonines, expanding the specificity of the GID complex. This resource of potential substrates and relationships between UPS components enables exploring functions of selective protein degradation.

Clinic-Pathological Characteristics and Prognostic Value of PD-L1 and HER2 in Gastric Cancer.

The aim of this study is to study the relationship between programmed cell death-1 ligand (PD-L1) and human epidermal growth receptor 2 (HER2) and the clinical-pathological features of gastric cancer (GC) and its predictive effect on the prognosis of gastric cancer (GC) patients. A retrospective analysis was performed on 113 patients undergoing GC surgery. The expression of PD-L1 and HER2 in GC and paired adjacent nontumor tissues was detected by immunohistochemistry or fluorescence in situ hybridization, and the relationships between PD-L1 and HER2 expression and clinical-pathological features and survival were analyzed by chi-square analysis, Pearson analysis, logistic regression analysis, Kaplan-Meier analysis, and Cox regression model. PD-L1 and HER2 were expressed in tumor tissues, but not in adjacent nontumor tissues. There was no correlation between the expression of PD-L1 and HER2. The expression of PD-L1 in GC was closely related to gender (p = 0.019), regional lymph node (p = 0.006), metastasis (p = 0.033), and survival status (p = 0.033), while HER2 was closely related to tumor differentiation (p = 0.033), regional lymph node (p = 0.016), and tumor-node-metastasis (TNM) stage (p = 0.036). The survival time of PD-L1-positive patients was longer than that of PD-L1-negative patients (p = 0.020). The expression of HER2 showed no difference in overall survival (p = 0.125). Multivariate analysis suggested that the TNM stage (p = 0.001) and PD-L1 expression (p = 0.047) were independent prognostic factors for survival time of GC. The expression of PD-L1 has biological significance in GC, which is closely related to the clinical-pathological characteristics and prognosis of GC patients.

Measurement of the Lower Lid Margin Thickness by Anterior Segment Optical Coherence Tomography.

PURPOSE: To verify the feasibility of using anterior segment optical coherence tomography (AS-OCT) to measure the lower lid margin thickness (LLMT) from posterior lash line to the mucocutaneous junction. METHODS: This was a prospective, single-center, observational study. Fifty-six volunteers between 20 and 79 years old with normal healthy eyes were included in this study. Using AS-OCT to measure the LLMT at the middle position was separately performed by two operators under the same conditions. RESULTS: The mean age of 56 subjects (24 males and 32 females) was 45.4 ± 15.7 years. The LLMT measured by AS-OCT between two operators was 0.86 ± 0.23 mm and 0.85 ± 0.22 mm, respectively. The reliability and repeatability between two operators were evaluated by intraclass correlation coefficient (ICC = 0.97). Based on one operator's measurements, the LLMT was 0.70 ± 0.10 mm at ages 20-29, 0.68 ± 0.09 mm at ages 30-39, 0.94 ± 0.12 mm at ages 40-49, 0.93 ± 0.20 mm at ages 50-59, 1.03 ± 0.15 mm at ages 60-69, and 1.24 ± 0.19 mm at ages 70-79, which indicated a significant positive correlation with age (rs = 0.74, p < 0.001). In addition, there was a significant difference in the LLMT between genders (0.94 ± 0.26 vs. 0.80 ± 0.19 mm, p = 0.03). CONCLUSIONS: A good agreement between two operators indicated that it seemed to be feasible to use AS-OCT to measure the LLMT. Additionally, we found that the LLMT appeared to be closely related to age and gender.

[Effects of aerobic exercise combined with Lycium ruthenicum on some indicators of myocardial lipid metabolism in rats with high-fat diet].

OBJECTIVE: To study the effects of aerobic exercise combined with Lycium ruthenicumon on some indicators of myocardial lipid metabolism in rats with high-fat diet. METHODS: Fifty-five male Wistar rats were subjected to adaptive feeding for 4 days and weight-free swimming training for 3 days, 20 min/d. After eliminating 5 rats that were not suitable for swimming training, the others were randomly divided into 5 groups according to their weight: regular diet + quiet control group (RDC), high fat diet + quiet control group (HDC), high-fat diet + Lycium ruthenicum quiet control group (HDLC), high fat diet + aerobic exercise group (HDM), high fat diet + Lycium ruthenicum + aerobic exercise group (HDLM), 10 in each group. Group HDM and HDLM did 60 min/d swimming training for 6 weeks with no-bearing. Group C were fed regular diet; The other groups were fed with high-fat diet; Group HDLC and HDLM were intragastrically treated with Lycium ruthenicum at the dose of 4.48 g/(kg·d), and the volume was 5 mL/kg, and the other groups were given equivalent distilled water. The Lee's index, serum and myocardial biochemical indexes were measured after 6 weeks. RESULTS: Compared with group RDC, Lee's index, serum free fatty acids (FFA), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), myocardial FFA and intercellular adhesion molecule-1 (ICAM-1) increased significantly (P＜0.01), serum level of high-density lipoprotein cholesterol (HDL-C) decreased significantly (P＜0.01) in group HDC. Compared with group HDC, Lee's index, serum FFA, IL-6, TNF-α, TC, TG, LDL-C, myocardial FFA and ICAM-1 decreased significantly (P＜0.05 or P＜0.01), serum HDL-C levels increased significantly (P＜0.05 or P＜0.01) in group HDLC, HDM and HDLM. Compared with group HDLC and HDM, Lee's index, serum FFA, IL-6, TNF-α, TC, TG, LDL-C, myocardial FFA and ICAM-1 decreased significantly (P＜0.05), serum HDL-C level increased significantly (P＜0.05) in group HDLM. CONCLUSION: Aerobic exercise and/or Lycium ruthenicum can improve lipid metabolism in rats with high-fat diet, reduce lipotoxicity caused by obesity. Combined intervention is more effective.

New Insight of Circular RNAs in Human Musculoskeletal Diseases.

Circular RNAs (circRNAs), a novel group of noncoding RNAs, are present in most eukaryotic cells. Different from messenger RNAs, circRNAs have a covalently closed single-stranded stable structure and often act in cell type and tissue-specific manners, indicating that they can be used as biomarkers. With the advance of high-throughput RNA sequencing technology and bioinformatics, a large number of circRNAs have been identified in association with musculoskeletal diseases, but the functions of most circRNAs have not been clarified. circRNAs regulate biological processes by adsorbing microRNA as "sponges," binding to proteins, acting as transcriptional regulators, and participating in translation of proteins. In this study, we discuss the latest understanding of biogenesis and gene regulatory mechanisms of circRNAs with special emphasis on new targets for musculoskeletal disease diagnosis and clinical treatment.

Male patients with TERT mutation may be more likely to benefit from immunotherapy, especially for melanoma.

Genomic mutation may be key factors for sex-biased disparities in cancer diagnosis, prognosis and prediction of treatment response. Current study has revealed that sex-based dimorphism on the efficacy of immune checkpoint inhibitors (ICIs) in various cancers and confirmed that male patients can benefit more from immunotherapy. However, only a subset of male patients responds well to ICIs. Therefore, biomarkers are desperately needed to identify the group of patients who may be more likely to benefit from ICIs. With the availability of the cBioPortal database, we identified that TERT mutation may serve as a sex-specific cancer biomarker and TERT mutation frequency of melanoma was higher in male patients. Notably, we found that male patients with TERT mutation may be more likely to benefit from immunotherapy (p = 0.006), especially for melanoma (p < 0.001). Therefore, our research provides a possible direction for the exploration of immunotherapy prediction biomarkers based on sex difference.

Identification of biomarkers associated with synovitis in rheumatoid arthritis by bioinformatics analyses.

OBJECTIVES: Rheumatoid arthritis (RA) is the most common inflammatory arthritis in the world, but its underlying mechanism is still unclear. The present study aims to screen and verify the potential biomarkers of RA. METHODS: We searched the Gene Expression Omnibus (GEO) database for synovial expression profiling from different RA microarray studies to perform a systematic analysis. Functional annotation of differentially expressed genes (DEGs) was conducted, including GO enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The protein-protein interaction (PPI) networks of the DEGs were constructed based on data from the STRING database. The expression levels of the hub genes in normal membranes and RA synovium were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot system. RESULTS: A total of 444 differential expression genes were identified, including 172 up-regulated and 272 down-regulated genes in RA synovium compared with normal controls. The top ten hub genes; protein tyrosine phosphatase receptor type C (PTPRC), LCK proto-oncogene (LCK), cell division cycle 20 (CDC20), Jun proto-oncogene (JUN), cyclin-dependent kinase 1 (CDK1), kinesin family member 11 (KIF11), epidermal growth factor receptor (epidermal growth factor receptor (EGFR), vascular endothelial growth factor A (VEGFA), mitotic arrest deficient 2 like 1 (MAD2L1), and signal transducer and activator of transcription 1 (STAT1) were identified from the PPI network, and the expression level of VEGFA and EGFR was significantly increased in RA membranes (P<0.05). CONCLUSION: Our results indicate that the hub genes VEGFA and EGFR may have essential effects during the development of RA and can be used as potential biomarkers of RA.

Study of Osteoarthritis-Related Hub Genes Based on Bioinformatics Analysis.

Osteoarthritis (OA) is a common cause of morbidity and disability worldwide. However, the pathogenesis of OA is unclear. Therefore, this study was conducted to characterize the pathogenesis and implicated genes of OA. The gene expression profiles of GSE82107 and GSE55235 were downloaded from the Gene Expression Omnibus database. Altogether, 173 differentially expressed genes including 68 upregulated genes and 105 downregulated genes in patients with OA were selected based on the criteria of ∣log fold-change | >1 and an adjusted p value < 0.05. Protein-protein interaction network analysis showed that FN1, COL1A1, IGF1, SPP1, TIMP1, BGN, COL5A1, MMP13, CLU, and SDC1 are the top ten genes most closely related to OA. Quantitative reverse transcription-polymerase chain reaction showed that the expression levels of COL1A1, COL5A1, TIMP1, MMP13, and SDC1 were significantly increased in OA. This study provides clues for the molecular mechanism and specific biomarkers of OA.