Low expression of ELOVL6 may be involved in fat loss in white adipose tissue of cancer-associated cachexia.

BACKGROUND: Cancer-associated cachexia (CAC) arises from malignant tumors and leads to a debilitating wasting syndrome. In the pathophysiology of CAC, the depletion of fat plays an important role. The mechanisms of CAC-induced fat loss include the enhancement of lipolysis, inhibition of lipogenesis, and browning of white adipose tissue (WAT). However, few lipid-metabolic enzymes have been reported to be involved in CAC. This study hypothesized that ELOVL6, a critical enzyme for the elongation of fatty acids, may be involved in fat loss in CAC. METHODS: Transcriptome sequencing technology was used to identify CAC-related genes in the WAT of a CAC rodent model. Then, the expression level of ELOVL6 and the fatty acid composition were analyzed in a large clinical sample. Elovl6 was knocked down by siRNA in 3T3-L1 mouse preadipocytes to compare with wild-type 3T3-L1 cells treated with tumor cell conditioned medium. RESULTS: In the WAT of patients with CAC, a significant decrease in the expression of ELOVL6 was found, which was linearly correlated with the extent of body mass reduction. Gas chromatographic analysis revealed an increase in palmitic acid (C16:0) and a decrease in linoleic acid (C18:2n-6) in these tissue samples. After treatment with tumor cell-conditioned medium, 3T3-L1 mouse preadipocytes showed a decrease in Elovl6 expression, and Elovl6-knockdown cells exhibited a reduction in preadipocyte differentiation and lipogenesis. Similarly, the knockdown of Elovl6 in 3T3-L1 cells resulted in a significant increase in palmitic acid (C16:0) and a marked decrease in oleic acid (C18:1n-9) content. CONCLUSION: Overall, the expression of ELOVL6 was decreased in the WAT of CAC patients. Decreased expression of ELOVL6 might induce fat loss in CAC patients by potentially altering the fatty acid composition of adipocytes. These findings suggest that ELOVL6 may be used as a valuable biomarker for the early diagnosis of CAC and may hold promise as a target for future therapies.

Additional suture augmentation to anterior cruciate ligament reconstruction with hamstring autografts bring no benefits to clinical results, graft maturation and graft-bone interface healing.

BACKGROUND: From the perspective of graft protection and early rehabilitation during the maturation and remodeling phases of graft healing, suture augmentation (SA) for anterior cruciate ligament reconstruction (ACLR) has attracted more and more attention. STUDY DESIGN: Retrospective study. PURPOSE: To determine whether the additional SA affects clinical results, graft maturation and graft-bone interface healing during two years follow-up after ACLR. METHODS: 20 ACLRs with additional SA (ACLR-SA group) and 20 ACLRs without additional SA (ACLR group) were performed between January 2020 and December 2021 by the same surgeon and were retrospectively analyzed. Pre- and postoperative International Knee Documentation Committee (IKDC) scores, Lysholm scores, graft failure and reoperation were evaluated. The signal/noise quotient (SNQ) of autografts and the signal intensity of graft-bone interface were analyzed. All 40 patients in ACLR-SA group and ACLR group completed 2-years follow-up. RESULTS: There was no patient in the two cohorts experienced graft failure and reoperation. The postoperative IKDC and Lysholm scores have been significantly improved compared with preoperative scored in both ACLR-SA group and ACLR group, however, there was no significant difference between two groups. The SNQ of proximal graft of ACLR-SA group (14.78 ± 8.62 vs. 8.1 ± 5.5, p = 0.041) was significantly greater while the grades of graft-bone interface healing of posterior tibial was significantly lower than that of ACLR group at 1-year postoperatively (p = 0.03), respectively. There were no significant differences between the two groups of the SNQ of proximal, distal medial graft segments, and the graft-bone interface healing grades of anterior femoral, posterior femoral, anterior tibial and posterior tibial at other time points (p>0.05). CONCLUSIONS: The additional SA in ACLR had no effect on IKDC scores, Lysholm scores, graft maturation and graft-bone interface healing at 2-year postoperatively. Our research does not support the routine use of SA in ACLR.

The efficacy of medial meniscal posterior Root tear Repair with or without high tibial osteotomy: a systematic review.

BACKGROUND: Medial meniscal posterior root tear (MMPRTs) is a common lesion of the knee joint, and repair surgery is a well-established treatment option. However, patients with obvious varus alignment are at an increased risk for MMPRT and can suffer from a greater degree of medial meniscus extrusion, which leads to the development of osteoarthritis following repair. The efficacy of high tibial osteotomy (HTO) as a means of correcting this malformation, and its potential benefits for MMPRT repair, remains unclear. PURPOSE: To explore whether HTO influenced the outcome of MMPRT repair in clinical scores and radiological findings. STUDY DESIGN: Systematic review. METHODS: According to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) guidelines, we searched PubMed, Embase, Web of Science, and the Cochrane Library databases for studies reporting the outcomes of MMPRT repair and extracted data about characteristics of patients, clinical functional scores and radiologic outcomes. One reviewer extracted the data and 2 reviewers assessed the risk of bias and performed a synthesis of the evidence. Articles were eligible if they reported the results of MMPRT repair with exact mechanical axis (registered in the International Prospective Register of Systematic Reviews, CRD42021292057). RESULTS: Fifteen studies with 625 cases of high methodological quality were identified. Eleven studies were assigned to the MMPRT repair group (M) with 478 cases performing MMPRT repair only, and others belonged to the MMPRT repair and HTO group (M and T) performing HTO and MMPRT repair. Most of the studies had significantly improved clinical outcome scores, especially in M groups. And the radiologic outcomes showed that the osteoarthritis deteriorated in both groups with similar degree in about 2-year follow-up. CONCLUSION: HTO is a useful supplement in treating MMPRT patients with severe osteoarthritis and the clinical and radiological outcomes were similar with MMPRT repair alone. Which would be better for patients' prognosis generally, performing MMPRT repair alone or a combination of HTO and MMPRT repair, was still controversial. We suggested taking K-L grade into account. Large-scale randomized control studies were called for in the future to help make better clinical decisions. LEVEL OF EVIDENCE: III.

Increased Lateral Femoral Condyle Ratio Measured by Magnetic Resonance Imaging Is Associated With Anterior Cruciate Ligament Rerupture.

PURPOSE: To investigate the association between lateral femoral condyle ratio (LFCR) measured by magnetic resonance imaging (MRI) and anterior cruciate ligament (ACL) rerupture after anatomic ACL reconstruction (ACLR) and to compare the diagnostic accuracy between MRI and radiograph measurements. METHODS: A retrospective review was conducted on patients who underwent anatomic ACLR in our institution between 2015 and 2018. Patients who experienced rerupture after ACLR were identified and matched 1:1 with control patients who showed no evidence of graft failure during a minimum 48-month follow-up. The matching criteria included age, sex, and body mass index. LFCR was measured on MRI scans and radiographs of the affected limb. Patients' characteristics, surgical features, and anatomic measurements were compared between groups. Conditional logistic regression was performed to investigate whether MRI-measured LFCR is a risk factor for ACL rerupture. The optimal cutoff value was determined by receiver operating characteristic curves (ROC). Delong's test was performed to compare the diagnostic accuracy between MRI and radiograph measurements. RESULTS: A total of 72 patients who sustained ACL rerupture were included and matched with 72 control subjects. Compared to patients with intact ACLR, those who sustained ACL rerupture showed a significant increase in LFCR on MRI scans (63.38% ± 2.26% [95% CI, 62.84%-63.91%] vs 61.10% ± 2.19% [95% CI, 60.59%-61.61%], P < .001). An MRI-measured LFCR >62.18% was set as the cutoff point to discern patients at a higher risk of graft failure after anatomic ACLR, with sensitivity and specificity of 75.0% and 70.8%, respectively. MRI-measured LFCR demonstrated superior diagnostic accuracy during ROC curve analysis, achieving a higher area under the curve compared to radiograph-measured LFCR (0.783 ± 0.051 vs 0.668 ± 0.060, P = .041). CONCLUSIONS: The study found that MRI-measured LFCR was associated with ACL rerupture. A cutoff value of 62.18% was determined, which can help identify patients at a higher risk of rerupture. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Arthroscopic Anatomical Double-Bundle Medial Patellofemoral Complex Reconstruction Improves Clinical Outcomes in Treating Recurrent Patellar Dislocation Despite Trochlear Dysplasia, Elevated Tibial Tubercle-Trochlear Groove Distance, and Patellar Alta.

PURPOSE: To evaluate the clinical outcomes of arthroscopically assisted double-bundle medial patellofemoral complex reconstruction (MPFC-R). METHODS: A retrospective review was carried out among adult patients who experienced at least 2 patellar dislocations and underwent primary arthroscopically assisted MPFC-R between January 2014 and November 2019. Dejour classification, tibial tubercle-trochlear groove (TT-TG) distance, and patellar height (with Insall-Salvati index) were measured. Pre- and postoperative patellar tilt were compared. Information on outcome scores, ability to return to sports, postoperative recurrent dislocations, and complications was recorded. RESULTS: A total of 42 MPFC-Rs in 39 patients were included. Mean age at surgery was 22.2 ± 7.6 years; 69.2% of patients were female. Mean follow-up was 47.3 ± 20.2 months. Seventy-four percent of cases had Dejour B (19.0%), C (33.3%), and D (21.4%) trochlear dysplasia; mean TT-TG distance was 19.6 ± 3.5 mm, and mean Insall-Salvati index was 1.21 ± 0.17. Mean patellar tilt decreased from 27.6 ± 11.6° to 9.4 ± 6.5° (P < .001). All patients had statistically significant (P < .001) improvement in mean International Knee Documentation Committee (IKDC) (44.9 ± 18.2 to 87.5 ± 6.9), Lysholm (61.4 ± 16.6 to 94.1 ± 6.4), Kujala (56.0 ± 16.8 to 92.9 ± 5.3), and Tegner score (2.7 ± 1.3 to 4.6 ± 1.4). The majority of patients (96.9%) returned to sports, with 90.3% returning to the same or greater level of activity. No postoperative dislocations or subluxations were reported. CONCLUSIONS: Arthroscopically assisted double-bundle MPFC-R is a promising procedure to treat recurrent patellar instability at 2- to 7-year mid-term follow-up, despite the presence of trochlear dysplasia, elevated TT-TG distance and patellar alta. The improvement of IKDC score exceeded the minimal clinically important difference in 95.2% patients, and 66.7% surpassed the patient acceptable symptomatic state based on postoperative IKDC score with no redislocations being reported at latest follow-up. LEVEL OF EVIDENCE: Level IV, case series, retrospective.

There is no difference in the efficacy of anterior cruciate ligament reconstruction using autograft combined with or without ligament augmentation: a systematic review and meta-analysis.

PURPOSE: This study aims to determine the efficacy of anterior cruciate ligament reconstruction (ACLR) using autograft combined with or without ligament augmentation. METHODS: A computerized search of the databases was conducted, including PubMed, Web of Science, Embase, Scopus and the Cochrane Library. Only prospective or retrospective comparative studies with a minimum 2-year follow-up were considered for inclusion. Two independent reviewers performed data extraction and methodological quality assessment. A Mantel-Haenszel analysis was used for the pooling of results. Sensitivity analysis was performed to maintain the stability of results. The egger test was applied to assess the publication bias. RESULTS: Fourteen studies were included. The total cohort was 1353 patients (non-augmented group: 763 patients; augmented group: 590 patients). There were three Randomized Controlled Trials (RCTs, Level I), six retrospective comparative studies (Level III) and five case-control studies (Level III). The follow-up rate was ≥ 88% and the follow-up periods were ≥ 24 months in all included studies. The augmented graft used to compare with autograft included the Ligament Augmentation Device (LAD), the Ligament Advanced Reinforcement System (LARS) artificial ligament, FiberTape, hamstring tendon allograft, degradable poly (urethane urea). No significant differences were observed between the augmented and non-augmented groups regarding postoperative patient-reported outcomes (PROs), including the International Knee Documentation Committee score, Lysholm score and Tegner score, knee laxity, including KT-1000, side-to-side difference, Lachman test and pivot shift and rate of graft failure. CONCLUSIONS: ACLR using autografts combined with ligament augmentation shows no advantages in PROs, knee laxity and graft failure rate compared with using autografts only. LEVEL OF EVIDENCE: Level III. TRIAL REGISTRATION: The research protocol was registered at the PROSPERO database (CRD42022324784).

The apex of the deep cartilage is a stable landmark to evaluate the femoral tunnel position in ACL reconstruction.

PURPOSE: To develop a simple and effective method for evaluating the femoral tunnel position using the apex of the deep cartilage (ADC) as the landmark. METHODS: A total of 52 patients who underwent arthroscopic ACL reconstruction were recruited between June and September 2021. The femoral tunnel was placed on the central point of the anteromedial footprint with an accessory anteromedial and a high anterolateral portal. Then, the length from the ADC to the shallow cartilage margin (L1) and to the center of the femoral tunnel (l1), as well as the center to the low cartilage margin (H1, intraoperative height), was measured under arthroscopy and on postoperative CT scans (L2, l2 and H2). Moreover, intraoperative and postoperative cartilage ratios were equivalent to l1/L1 and l2/L2, respectively. Linear regression, Pearson correlation and Bland-Altman analysis were performed to evaluate the consistency between these two measurements of cartilage ratio (l/L) and height (H). RESULTS: The mean age at the time of surgery was 28.7 years; 42 patients were male, and 17 patients were hurt in the left knee among 52 patients. The intraoperative cartilage ratio was 0.37 ± 0.04, and the height was 8.1 ± 1.1 mm with almost perfect inter-observer reproducibility. After the surgery, the cartilage ratio and height were measured as 0.39 ± 0.04 and 8.2 ± 1.3 mm on 3D-CT, respectively, with almost perfect intra- and inter-observer reproducibility. Significant positive correlations and linear regression were detected in the cartilage ratio (r = 0.844, p < 0.001), and height (r = 0.926, p < 0.001) intraoperatively and postoperatively. The Bland-Altman plot also showed excellent consistency between arthroscopy and 3D-CT. CONCLUSIONS: The ADC is a good landmark in the assessment of femoral tunnel position, with excellent consistency between intraoperative arthroscopic measurements and postoperative 3D-CT. CLINICALTRIALS: gov Identifier: NCT04937517. LEVEL OF EVIDENCE: Level III.

The apex of the deep cartilage is a stable landmark to position the femoral tunnel during remnant-preserving anterior cruciate ligament reconstruction.

PURPOSE: The aim of this retrospective cohort study was to investigate whether the apex of the deep cartilage (ADC) could help surgeons position the femoral tunnel accurately in remnant-preserving anterior cruciate ligament (ACL) reconstruction (ACLR). METHODS: In the current retrospective cohort study, a total of 134 patients who underwent ACLR between 2016 and 2020 were included. The femoral tunnel position was located using ADC as the landmark. The patients were divided into two groups: the remnant-preserving group (RP group, n = 68) underwent remnant-preserving ACLR, and the nonremnant group (NRP group, n = 66) underwent traditional ACLR with remnant removal. Postoperatively, the femoral tunnel position was evaluated on 3D-CT. The length from the ADC to the shallow cartilage margin (L) and to the centre of the femoral tunnel (l) and the length from the centre of the femoral tunnel to a low cartilage ratio in the direction from high to low (H) were measured. RESULTS: The l/L values of the RP and NRP groups were both 0.4 ± 0.1 after rounding (n.s.), and the H values were 9.3 ± 1.6 mm and 9.3 ± 1.7 mm, respectively (n.s.). There was no significant difference in l/L or H between the two groups. The estimation plot also showed high consistency of H and l/L of the two groups. The inter- and intraobserver reliability of I, L, l/L, and H were almost perfect. CONCLUSIONS: The apex of the deep cartilage is a good landmark for positioning the femoral tunnel in remnant-preserving ACL reconstruction. LEVEL OF EVIDENCE: Level III.

A comparative study of modern total ankle replacement and ankle arthrodesis for ankle osteoarthritis at different follow-up times: a systematic review and meta-analysis.

PURPOSE: Total ankle replacement (TAR) or ankle arthrodesis (AA) is the main surgical treatment for end-stage ankle osteoarthritis. However, the therapeutic effect of the two surgical procedures at different follow-up times remains controversial. The purpose of this meta-analysis is to compare the short-term, medium-term, and long-term safety and efficiency of the two modern surgical treatments. METHODS: We conducted a comprehensive search in PubMed, EMBASE, Cochrane library databases, Web of Science, and Scopus. The main results were the patient's reported outcome measure (PROM) score, satisfaction, complications, reoperation, and surgery success rate. Different follow-up times and implant designs were used to evaluate the source of heterogeneity. We used a fixed effects model for meta-analysis and I2 statistic for evaluating heterogeneity. RESULTS: Thirty-seven comparative studies were included. In the short term, TAR significantly improved clinical scores (AOFAS score: WMD = 7.07, 95% Cl: 0.41-13.74, I2 = 0.0%; SF-36 PCS score: WMD = 2.40, 95% Cl: 2.22-2.58, I2 = 0.0%; SF-36 MCS score: WMD = 0.40, 95% Cl: 0.22-0.57, I2 = 0.0%; VAS for pain: WMD = - 0.50, 95% Cl: - 0.56-0.44, I2 = 44.3%) and had the lower incidence of revision (RR = 0.43, 95% CI: 0.23-0.81, I2 = 0.0%) and complications (RR = 0.67, 95% Cl: 0.50-0.90, I2 = 0.0%). In the medium term, there were still higher improvements in both the clinical scores (SF-36 PCS score: WMD = 1.57, 95% Cl: 1.36-1.78, I2 = 20.9%; SF-36 MCS score: WMD = 0.81, 95% Cl: 0.63-0.99, I2 = 48.8%) and the patient satisfaction (RR = 1.24, 95% Cl: 1.08-1.41, I2 = 12.1%) in the TAR group, but its total complications rate (RR = 1.84, 95% Cl: 1.26-2.68, I2 = 14.9%) and revision rate (RR = 1.58, 95% CI: 1.17-2.14, I2 = 84.6%) were significantly higher than that of the AA group. In the long term, there was no significant difference in clinical score and satisfaction, and a higher incidence of revision (RR = 2.32, 95% Cl: 1.70-3.16, I2 = 0.0%) and complications (RR = 3.18, 95% Cl: 1.69-5.99, I2 = 0.0%) was observed in TAR than in AA. The result of the third-generation design subgroup was consistent with that of the above pooled results. CONCLUSION: TAR had advantages over AA in the short term due to better performance in terms of PROMs, complications, and reoperation rates, but its complications become a disadvantage in the medium term. In the long term, AA seems to be favored because of lower complications and revision rates, although there is no difference in clinical scores.

Phosphorylated LASS2 inhibits prostate carcinogenesis via negative regulation of Wnt/ß-catenin signaling.

LASS2 is a novel tumor-suppressor gene and has been characterized as a ceramide synthase, which synthesizes very-long acyl chain ceramides. However, LASS2 function and pathway-related activity in prostate carcinogenesis are still largely unexplored. Here, we firstly report that LASS2 promotes ß-catenin degradation through physical interaction with STK38, SCYL2, and ATP6V0C via the ubiquitin-proteasome pathway, phosphorylation of LASS2 is essential for ß-catenin degradation, and serine residue 248 of LASS2 is illustrated to be a key phosphorylation site. Furthermore, we find that dephosphorylation of LASS2 at serine residue 248 significantly enhances prostate cancer cell growth and metastasis in vivo, indicating that phosphorylated LASS2 inhibits prostate carcinogenesis through negative regulation of Wnt/ß-catenin signaling. Thus, our findings implicate LASS2 as a potential biomarker and therapeutic target of prostate cancer.

Long noncoding RNA MIR99AHG promotes gastric cancer progression by inducing EMT and inhibiting apoptosis via miR577/FOXP1 axis.

BACKGROUND: Long non-coding RNAs (lncRNAs) play a vital role in the genesis and development of human cancer. LncRNA MIR99AHG has been reported to be upregulated in acute myeloid leukemia (AML); however, its function in gastric cancer (GC) is still not clear. Here we were aiming to screen the prognostic lncRNA candidates and to explore the function of MIR99AHG in GC. METHODS: We have preliminarily screened some candidate lncRNA biomarkers in GC tissues through analyzing microarray datasets. The expression level of MIR99AHG in GC cell lines and tissues was monitored via qPCR. Survival analysis was performed with the patients of our hospital and TCGA database cases. CCK-8 assay, trans-well assay and flow cytometry were performed to determine cell proliferation, invasion, migration and apoptosis. Meanwhile, a target of MIR99AHG was predicted and identified by luciferase reporter gene detection experiments. RESULTS: MIR99AHG was strongly up-regulated in human GC and contributed to cancer progression. Kaplan-Meier analysis revealed that up-regulating MIR99AHG expression was positively correlated with unfavorable overall survival (P < 0.01) of patients from our hospital and TCGA database. Knockdown of MIR99AHG expression inhibited cell proliferation, invasion, migration and promoted cell apoptosis. Moreover, MIR99AHG worked as an oncogenic gene though competing for endogenous RNA (ceRNA) of miR-577. CONCLUSIONS: Our findings suggested that MIR99AHG contributes to malignant phenotypes of GC and may become a promising therapeutic target.

Cachexia-related long noncoding RNA, CAAlnc1, suppresses adipogenesis by blocking the binding of HuR to adipogenic transcription factor mRNAs.

Cancer-associated cachexia (CAC) is a devastating syndrome characterized by progressive losses of adipose tissue and skeletal muscle. CAC-related adipose tissue loss (CAL) occurs early and is associated with a shorter survival time. To explore potential regulatory long noncoding RNAs (lncRNAs) of CAL, RNA microarrays were used to analyze the transcriptomes of white adipose tissue from CAC mice vs. control mice. A set of differentially expressed lncRNAs was identified, and among them was CAAlnc1, which suppressed adipogenesis of C3H10 cells as demonstrated by gain-of-function and loss-of-function experiments. RNA immunoprecipitation and pull-down assays revealed Hu antigen R (HuR) was an important binding partner of CAAlnc1. The interaction between CAAlnc1 and HuR blocked the binding of HuR to adipogenic transcription factor mRNAs and further downregulated the expression of these transcription factors. This study generated a list of CAL-related lncRNAs and provided details of a functional lncRNA which may play an important role in CAL.

Investigation of the Pressure Gain Characteristics and Cycle Performance in Gas Turbines Based on Interstage Bleeding Rotating Detonation Combustion.

To further improve the cycle performance of gas turbines, a gas turbine cycle model based on interstage bleeding rotating detonation combustion was established using methane as fuel. Combined with a series of two-dimensional numerical simulations of a rotating detonation combustor (RDC) and calculations of cycle parameters, the pressure gain characteristics and cycle performance were investigated at different compressor pressure ratios in the study. The results showed that pressure gain characteristic of interstage bleeding RDC contributed to an obvious performance improvement in the rotating detonation gas turbine cycle compared with the conventional gas turbine cycle. The decrease of compressor pressure ratio had a positive influence on the performance improvement in the rotating detonation gas turbine cycle. With the decrease of compressor pressure ratio, the pressurization ratio of the RDC increased and finally made the power generation and cycle efficiency enhancement rates display uptrends. Under the calculated conditions, the pressurization ratios of RDC were all higher than 1.77, the decreases of turbine inlet total temperature were all more than 19 K, the power generation enhancements were all beyond 400 kW and the cycle efficiency enhancement rates were all greater than 6.72%.

Interleukin-6 induces fat loss in cancer cachexia by promoting white adipose tissue lipolysis and browning.

BACKGROUND: Cancer cachexia is a progressive and multi-factorial metabolic syndrome characterized by loss of adipose tissue and skeletal muscle. White adipose tissue (WAT) lipolysis and white-to-brown transdifferentiation of WAT (WAT browning) are proposed to contribute to WAT atrophy in cancer cachexia. Chronic inflammation, mediated by cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), has been reported to promote cancer cachexia. However, whether chronic inflammation promotes cancer cachexia by regulating WAT metabolism and the underlying mechanism remains unclear. METHODS: In this study, we first analyzed the association between chronic inflammation and WAT metabolism in gastric and colorectal cancer cachectic patients. In cachectic mice treated with anti-IL-6 receptor antibody, we clarified whether WAT lipolysis and browning were regulated by IL-6. RESULTS: Clinical analyses showed positive significant association between serum IL-6 and free fatty acid (FFA) both in early- and late-stage cancer cachexia. However, serum TNF-α was positively associated with serum FFA in the early- but not late-stage cachexia. WAT lipolysis was increased in early- and late-stage cachexia, while WAT browning was detected only in late-stage cachexia. Anti-IL-6 receptor antibody inhibited WAT lipolysis and browning in cachectic mice. CONCLUSIONS: Based on these findings, we conclude that chronic inflammation (especially that mediated by IL-6) might promote cancer cachexia by regulating WAT lipolysis in early-stage cachexia and browning in late-stage cachexia.

MicroRNA-425-5p regulates chemoresistance in colorectal cancer cells via regulation of Programmed Cell Death 10.

Acquired chemoresistance represents a major obstacle in cancer treatment, the underlying mechanism of which is complex and not well understood. MiR-425-5p has been reported to be implicated tumorigenesis in a few cancer types. However, its role in regulating chemoresistance has not been investigated in colorectal cancer (CRC) cells. Microarray analysis was performed in isogenic chemosensitive and chemoresistant HCT116 cell lines to identify differentially expressed miRNAs. miRNA quantitative real-time PCR was used to detect miR-425-5p expression levels between drug resistant and parental cancer cells. MiR-425-5p mimic and inhibitor were transfected, followed by CellTiter-Glo(®) assay to examine drug sensitivity in these two cell lines. Western Blot and luciferase assay were performed to investigate the direct target of miR-425-5p. Xenograft mouse models were used to examine in vivo function of miR-425-5p. Our data showed that expression of miR-425-5p was significantly up-regulated in HCT116-R compared with parental HCT116 cells. Inhibition of miR-425-5p reversed chemoresistance in HCT116-R cells. Programmed cell death 10 (PDCD10) is the direct target of miR-425-5p which is required for the regulatory role of miR-425-5p in chemoresistance. MiR-425-5p inhibitor sensitized HCT116-R xenografts to chemo drugs in vivo. Our study demonstrated that miR-425-5p regulates chemoresistance of CRC cells by modulating PDCD10 expression level both in vitro and in vivo. MiR-425-5p may represent a new therapeutic target for the intervention of CRC.

Silencing of miR-101 Prevents Cartilage Degradation by Regulating Extracellular Matrix-related Genes in a Rat Model of Osteoarthritis.

Osteoarthritis (OA) is a common, degenerative joint disease characterized by articular cartilage degradation. Currently, clinical trials based on microRNA therapy have been performed to treat various diseases. However, no treatment has been found for arthritis. This study investigated the functions of miR-101 in cartilage degradation in vivo and evaluated the feasibility of using miR-101 as a therapeutic agent for OA. Mono-iodoacetate-induced arthritis (MIA) rats were used as an animal model of OA. miR-101 mimic or miR-101 inhibitor was injected into the rats' knees to evaluate its effects on cartilage degradation. Cartilage degradation aggravated at 14 days after the injection of miR-101 mimic. By contrast, miR-101 silencing reduced cartilage degradation. Moreover, the administration of miR-101 mimic is sufficient to cause cartilage degradation in the normal cartilage of rats. By contrast, miR-101 inhibitor could prevent this change. Microarray and qPCR were used to investigate the different expressed genes after injecting miR-101 mimic and miR-101 inhibitor in the rats' articular cartilage. Several cartilage degradation-related genes were selected and validated to function in cartilage degradation with miR-101. Our results demonstrated the therapeutic effect of miR-101 inhibition on cartilage degradation in MIA rats by regulating several cartilage degradation-related genes.

Microwave Imaging under Oblique Illumination.

Microwave imaging based on inverse scattering problem has been attracting many interests in the microwave society. Among some major technical challenges, the ill-posed, multi-dimensional inversion algorithm and the complicated measurement setup are critical ones that prevent it from practical applications. In this paper, we experimentally investigate the performance of the subspace-based optimization method (SOM) for two-dimensional objects when it was applied to a setup designed for oblique incidence. Analytical, simulation, and experimental results show that, for 2D objects, neglecting the cross-polarization scattering will not cause a notable loss of information. Our method can be potentially used in practical imaging applications for 2D-like objects, such as human limbs.

Comparison of Clinical Outcomes Between Modern Augmented ACL Repair and Autograft ACL Reconstruction: A Systematic Review and Meta-analysis of Studies With Minimum 2-Year Follow-up.

Background: Anterior cruciate ligament (ACL) reconstruction has been the gold standard for primary ACL rupture since the 1990s. In the past decade, ACL repair has received renewed attention and increased research. Purpose: To compare the clinical outcomes of modern augmented ACL repair versus autograft reconstruction for ACL ruptures. Study Design: Systematic review; Level of evidence, 3. Methods: A search of the PubMed, EMBASE, Scopus, Web of Science, and the Cochrane Library databases was conducted for prospective or retrospective comparative studies published between January 1, 2010, and January 3, 2023, with a minimum 2-year follow-up. Two independent reviewers performed data extraction and methodological quality assessment. Sensitivity analysis was performed to maintain the stability of results. Results: Nine studies were included (minimum follow-up period, 24-60 months). The total sample size was 833 patients (augmented repair group: 358 patients; autograft ACL reconstruction group: 475 patients). There were 4 randomized controlled trials (level 1), 1 prospective comparative study (level 2), 2 retrospective comparative studies (level 3), and 2 case-control studies (level 3). The augmented ACL repair group attained significantly higher Lysholm score (weighted mean difference [WMD] = 1.57; 95% confidence interval [CI], 0.14-3.01; P = .03) and hamstring strength (WMD = 36.69; 95% CI, 29.07-44.31; P < .01) but had higher rates of hardware removal (odds ratio [OR] = 6.30; 95% CI, 2.44-16.23; P = .0001), reoperation (OR = 1.87; 95% CI, 1.33-2.62; P = .0003), and failure (OR = 1.58; 95% CI, 1.03-2.43; P = .0003) compared with the autograft ACL reconstruction group. No significant differences were observed between the repair and reconstruction groups regarding postoperative International Knee Documentation Committee scores, Tegner scores, knee laxity, satisfaction, ACL revisions, complications, and reoperation rather than revision. Conclusion: Augmented ACL repair was associated with higher rates of reoperation, hardware removal, and failure compared with autograft ACL reconstruction in studies with minimum 2-year follow-up data. However, augmented ACL repair had higher Lysholm scores and hamstring strength versus autograft ACL reconstruction.

Identification of the inhibition mechanism of carbonic anhydrase II by fructooligosaccharides.

Polygonatum sibiricum (P. sibiricum), recognized as a precious nourishing Chinese traditional medicine, exhibits the pharmacological effect of anti-aging. In this work, we proposed a novel mechanism underlying this effect related to the less studied bioactive compounds fructooligosaccharides in P. sibiricum (PFOS) to identify the inhibition effect of the small glycosyl molecules on the age-related zinc metalloprotease carbonic anhydrase II (CA II). Molecular docking and molecular dynamics simulation were used to investigate the structural and energetic properties of the complex systems consisting of the CA II enzyme and two possible structures of PFOS molecules (PFOS-A and PFOS-B). The binding affinity of PFOS-A (-7.27 ± 1.02 kcal/mol) and PFOS-B (-8.09 ± 1.75 kcal/mol) shows the spontaneity of the binding process and the stability of the combination in the solvent. Based on the residue energy decomposition and nonbonded interactions analysis, the C-, D- and G-sheet fragments of the CA II were found to be crucial in binding process. Van der Waals interactions form on the hydrophobic surface of CAII mainly with 131PHE and 135VAL, while hydrogen bonds form on the hydrophilic surface mainly with 67ASN and 92GLN. The binding of PFOS results in the blocking of the zinc ions pocket and then inhibiting its catalytic activity, the stability of which has been further demonstrated by free energy landscape. These findings provide evidence of the effective inhibition of PFOS to CA II enzyme, which leads to a novel direction for exploring the mechanism of traditional Chinese medicine focused on small molecule fructooligosaccharides.

An electrochemiluminescence aptasensor based on Ti3C2 QDs-1T/2H MoS2 nano-hybrid material for the highly sensitive detection of lincomycin.

Developing a highly selective and sensitive analysis strategy for lincomycin (LIN) is of great significance for environmental protection and food safety. Herein, we reported a novel electrochemiluminescence (ECL) aptasensor based on Ti3C2 QDs-1T/2H MoS2 nano-hybrid luminophore for detection of LIN. The hybridization of Ti3C2 QDs and 1T/2H MoS2 endowed nanocomposite with structural and compositional advantages for boosting the ECL performance of QDs by about three times. This enhancement could be attributed to the remarkable electrocatalytic activity and high conductivity exhibited by 1T/2H MoS2. Secondly, the great surface area of 1T/2H MoS2 is conducive to the high dispersion of Ti3C2 QDs, and its good conductivity could promote charge transfer. On the other hand, the excellent catalytic performance of 1T/2H MoS2 could facilitate the reduction of S2O82- to produce more radical, which significantly enhance the ECL signal of Ti3C2 QDs. Given these features, a sensor for detection of LIN was established based on specific recognition between target and aptamer. The sensor showed a good linear relationship (0.05 ng mL-1 ∼100 µg mL-1) with a detection limit as low as 0.02 ng mL-1. It is worth noting that this work has been validated in testing milk samples, exhibiting great potential application prospects in food analysis.