Biomechanical characteristic differences of two new types of intramedullary nail devices in the treatment of comminuted intertrochanteric fractures of femur: a comparative study based on finite element analysis.

OBJECTIVE: Given the recent application of two new types of intramedullary nail devices in the treatment of comminuted femoral intertrochanteric fractures (CFIFs), there is still a lack of deep understanding and comparative evaluation of their biomechanical properties. Therefore, this study aims to systematically compare the advantages and disadvantages of these two new devices with traditional proximal femoral nail antirotation (PFNA) and InterTan nails in the fixation of CFIFs through finite element analysis. METHODS: Based on the validated finite element model, this study constructed an accurate CFIFs model. In this model, PFNA, InterTan nails, proximal femoral bionic nails (PFBN), and new intramedullary systems (NIS) were implanted, totaling four groups of finite element models. Each group of models was subjected to simulation tests under a vertical load of 2100 N to evaluate the displacement and Von Mises stress (VMS) distribution of the femur and intramedullary nail devices. RESULTS: Under a vertical load of 2100 N, a comparative analysis of the four finite element models showed that the NIS device exhibited the most superior performance in terms of peak displacement, while the PFNA device performed relatively poorly. Although the NIS device had the highest peak stress in the femur, it had the smallest peak displacement of both the femur and intramedullary nail devices, and the peak stress was mainly concentrated on the lateral side of the femur, with significantly lower stress in the proximal femur compared to the other three intramedullary nail devices. In contrast, the PFBN device had the lowest peak stress in the femur, and its peak displacement of both the femur and intramedullary nail devices was also less than that of PFNA and InterTan nails. CONCLUSION: This study demonstrates that in the treatment of CFIFs, PFBN and NIS devices exhibit superior biomechanical performance compared to traditional PFNA and InterTan nail devices. Especially the NIS device, which can achieve good biomechanical results when fixing femoral intertrochanteric fractures with missing medial wall. Therefore, both PFBN and NIS devices can be considered reliable closed reduction and internal fixation techniques for the treatment of CFIFs, with potential clinical application value.

Safety and efficacy of side-by-side versus stent-in-stent stenting for malignant hilar biliary obstruction: a systematic review and meta-analysis.

Objectives: Stenting of the malignant hilar biliary obstruction (MHBO) area for bile drainage is challenging. Bilateral stenting techniques of stent-in-stent (SIS) and stent-by-stent (SBS) have shown promising results. This study evaluates the efficacy of different stenting methods for MHBO. Design: A meta-analysis was performed to determine the efficacy of SIS and SBS stenting strategies for MHBO. Data sources and methods: Medical databases such as PubMed, Web of Science, Embase, and Scopus, were searched up to August 2023. We selected eligible studies reporting the data on technical and clinical success, adverse events, and incidence of re-obstruction (RO) of SBS and SIS groups in MHBO patients. We compared the outcomes of SBS and SIS groups. Results: A total of 9 studies comparing the data of 545 patients (268 in the SBS group and 277 in the SIS stenting group) were analyzed. There was no significant difference (p > 0.05) in the odds ratio (OR) of Re-obstruction (RO) 0.87 (95% confidence interval (95% CI) 0.6-1.25), technical success 0.58 (95% CI 0.16-2.11), clinical success 1.13 (95% CI 0.62-2.07), and adverse events 1.53 (95% CI 0.88-2.64). The mean difference in procedure time was -12.25 min (95% CI -18.39, -6.12), and the hazard ratio of stent patency was 1.22 (95% CI 1.01-1.47), favoring SBS, with high heterogeneity (I 2 = 94%). There was no significant difference in HR for survival 1.05 (95% CI 0.95-1.16) with high heterogeneity (I 2 = 84%). Conclusion: Compared with SIS, SBS showed better stent patency with comparable technical and clinical success and adverse events. Prospero registration: The registration number for this study on PROSPERO is CRD42024523230.

IL-10R inhibition reprograms tumor-associated macrophages and reverses drug resistance in multiple myeloma.

Multiple myeloma (MM) is the cancer of plasma cells within the bone marrow and remains incurable. Tumor-associated macrophages (TAMs) within the tumor microenvironment often display a pro-tumor phenotype and correlate with tumor proliferation, survival, and therapy resistance. IL-10 is a key immunosuppressive cytokine that leads to recruitment and development of TAMs. In this study, we investigated the role of IL-10 in MM TAM development as well as the therapeutic application of IL-10/IL-10R/STAT3 signaling inhibition. We demonstrated that IL-10 is overexpressed in MM BM and mediates M2-like polarization of TAMs in patient BM, 3D co-cultures in vitro, and mouse models. In turn, TAMs promote MM proliferation and drug resistance, both in vitro and in vivo. Moreover, inhibition of IL-10/IL-10R/STAT3 axis using a blocking IL-10R monoclonal antibody and STAT3 protein degrader/PROTAC prevented M2 polarization of TAMs and the consequent TAM-induced proliferation of MM, and re-sensitized MM to therapy, in vitro and in vivo. Therefore, our findings suggest that inhibition of IL-10/IL-10R/STAT3 axis is a novel therapeutic strategy with monotherapy efficacy and can be further combined with current anti-MM therapy, such as immunomodulatory drugs, to overcome drug resistance. Future investigation is warranted to evaluate the potential of such therapy in MM patients.

Endoscopic treatment for early duodenal papillary carcinoma: long-term outcomes.

BACKGROUND AND AIM: This study aims to determine whether endoscopic papillectomy (EP) is a safe and effective treatment for early duodenal papillary carcinoma with long-term follow-up. METHODS: From June 2012 to September 2022, 48 patients with early duodenal papilloma carcinoma who received endoscopic treatment were included. The histological types, percentage of complete resections, postoperative residuals, adverse events, and recurrences were evaluated. RESULTS: EP was successful in all patients; 46 were lumped, and two were fragmented, with a 95.8% intact removal rate (46/48). The preoperative biopsy pathological positive rate was 70.8% (34/48). The incidence of early postoperative adverse events (within 1 month after EP) were 16.7% (8/48), including four cases of acute pancreatitis, three cases of delayed bleeding, and one case of acute cholangitis. In addition, 4.2% (2/48) of the late adverse events were bile duct stenosis. After 6 months, the postoperative residual rate was 0%. The median time to recurrence was 17.5 months, and the postoperative recurrence rate was 16.7% (8/48) in patients treated with radiofrequency ablation. The median progression-free survival was 18.6 months (95% CI, 12.1-25.1), and the median overall survival was 121.5 months (95% CI, 105.6-120.9). CONCLUSIONS: EP is a safe and efficient alternative therapy for early duodenal papillary carcinoma. Endoscopic follow-up and treatment are essential because of the potential for recurrence.

Potential of novel iron 1,3,5-benzene tricarboxylate loaded on biochar to reduce ammonia and nitrous oxide emissions and its associated biological mechanism during composting.

In this study, a novel iron 1,3,5-benzene tricarboxylate loaded on biochar (BC-FeBTC) was developed and applied to kitchen waste composting. The results demonstrated that the emissions of NH3 and N2O were significantly reduced by 57.2% and 37.8%, respectively, compared with those in control group (CK). Microbiological analysis indicated that BC-FeBTC addition altered the diversity and abundance of community structure as well as key functional genes. The nitrification genes of ammonia-oxidizing bacteria were enhanced, thereby promoting nitrification and reducing the emission of NH3. The typical denitrifying bacterium, Pseudomonas, and critical functional genes (nirS, nirK, and nosZ) were significantly inhibited, contributing to reduced N2O emissions. Network analysis further revealed the important influence of BC-FeBTC in nitrogen transformation driven by functional microbes. These findings offer crucial scientific foundation and guidance for the application of novel materials aimed at mitigating nitrogen loss and environmental pollution during composting.

Development of machine learning prognostic models for overall survival of prostate cancer patients with lymph node-positive.

Prostate cancer (PCa) patients with lymph node involvement (LNI) constitute a single-risk group with varied prognoses. Existing studies on this group have focused solely on those who underwent prostatectomy (RP), using statistical models to predict prognosis. This study aimed to develop an easily accessible individual survival prediction tool based on multiple machine learning (ML) algorithms to predict survival probability for PCa patients with LNI. A total of 3280 PCa patients with LNI were identified from the Surveillance, Epidemiology, and End Results (SEER) database, covering the years 2000-2019. The primary endpoint was overall survival (OS). Gradient Boosting Survival Analysis (GBSA), Random Survival Forest (RSF), and Extra Survival Trees (EST) were used to develop prognosis models, which were compared to Cox regression. Discrimination was evaluated using the time-dependent areas under the receiver operating characteristic curve (time-dependent AUC) and the concordance index (c-index). Calibration was assessed using the time-dependent Brier score (time-dependent BS) and the integrated Brier score (IBS). Moreover, the beeswarm summary plot in SHAP (SHapley Additive exPlanations) was used to display the contribution of variables to the results. The 3280 patients were randomly split into a training cohort (n = 2624) and a validation cohort (n = 656). Nine variables including age at diagnosis, race, marital status, clinical T stage, prostate-specific antigen (PSA) level at diagnosis, Gleason Score (GS), number of positive lymph nodes, radical prostatectomy (RP), and radiotherapy (RT) were used to develop models. The mean time-dependent AUC for GBSA, RSF, and EST was 0.782 (95% confidence interval [CI] 0.779-0.783), 0.779 (95% CI 0.776-0.780), and 0.781 (95% CI 0.778-0.782), respectively, which were higher than the Cox regression model of 0.770 (95% CI 0.769-0.773). Additionally, all models demonstrated almost similar calibration, with low IBS. A web-based prediction tool was developed using the best-performing GBSA, which is accessible at https://pengzihexjtu-pca-n1.streamlit.app/ . ML algorithms showed better performance compared with Cox regression and we developed a web-based tool, which may help to guide patient treatment and follow-up.

Correlation between prescribing doctor attributes and intestinal cleanliness in colonoscopy: a study of 22522 patients.

OBJECTIVE: This study aimed to analyze the correlation between different attributes of doctors who prescribe colonoscopies and the cleanliness of the intestine to guide the development of colonoscopy application protocols. METHODS: Data on colonoscopy cases conducted in the gastroenterology department of Hangzhou First People's Hospital between April 2018 and March 2021 were collected. The gender, age, professional attributes of the prescribing doctors, and Boston Bowel Preparation Scale (BBPS) score were recorded. In addition, the correlation between the prescribing doctors' characteristics and the intestine's cleanliness was analyzed. RESULTS: The study included 22,522 patients with a mean BBPS score of 6.83 ± 1.94. There were 16,459 male and 6,063 female doctors with similar BBPS scores (p = 0.212). The study found no significant difference in BBPS scores between 19,338 internist and 3,184 non-internist (p = 0.154). However, BBPS scores differed significantly between 18,168 gastroenterologists and 4,354 non-gastroenterologists (p = 0.016) and between 19,990 intestinal-related specialties(gastroenterology and gastrointestinal surgery) and 2,532 non-intestinal-related specialties (p = 0.000). In addition, BBPS scores were significantly different between 18,126 prescribing endoscopiests and 4,396 non-endoscopiests (p = 0.014). However, there was no significant difference in BBPS scores among doctors of different ages (p = 0.190). The study found significant differences in BBPS scores between male and female patients and those under or over 40 years (p = 0.000). CONCLUSION: To improve colonoscopy preparation quality, priority should be given to doctors in gastroenterology, intestinal-related specialties, and endoscopiests. Their expertise may result in better education and improved bowel cleanliness.

Receptor tyrosine kinases Tyro3, Axl, and Mertk differentially contribute to antibody-induced arthritis.

Tyro3, Axl, and Mertk (abbreviated TAMs) comprise a family of homologous type 1 receptor tyrosine kinases (RTKs) that have been implicated as inhibitory receptors that dampen inflammation, but their roles in the pathogenesis of rheumatoid arthritis remains understudied. Here, to investigate TAMs in an inflammatory arthritis model, antibody-induced arthritis in single TAM-deficient mice (Tyro3- KO, Axl-KO, Mertk-KO) was induced by K/BxN serum injection. Subsequently, joint inflammation and cytokine levels, as well as the expression of Fcγ Rs and complement receptors were assessed in WT and TAM-deficient mice. Compared with littermate control mice, Axl-/- and Mertk-/- mice developed more severe antibody-induced arthritis, while in contrast, Tyro3-/- mice showed diminished joint inflammation. Concomitantly, the levels of cytokines in joints of Axl-/- and Mertk-/- mice were also significantly increased, while cytokines in the Tyro3-/- joint tissues were decreased. At the molecular and cellular level, TAMs showed distinct expression patterns, whereby monocytes expressed Axl and Mertk, but no Tyro3, while neutrophils expressed Axl and Tyro3 but little Mertk. Moreover, expression of Fcγ receptors and C5aR showed different patterns with TAMs expression, whereby FcγRIV was higher in monocytes of Axl-/- and Mertk-/- mice compared to wild-type mice, while Tyro3-/- neutrophils showed lower expression levels of FcγRI, FcγRIII and FcγRIV. Finally, expression of C5aR was increased in Mertk-/- monocytes, and was decreased in Tyro3-/- neutrophils. These data indicate that Axl, Mertk and Tyro3 have distinct functions in antibody-induced arthritis, due in part to the differential regulation of cytokines production, as well as expression of FcγRs and C5aR. Video Abstract.

IL-13-induced STAT3-dependent signaling networks regulate esophageal epithelial proliferation in eosinophilic esophagitis.

BACKGROUND: Basal zone hyperplasia (BZH) and dilated intercellular spaces (DISs) are thought to contribute to the clinical manifestations of eosinophilic esophagitis (EoE); however, the molecular pathways that drive BZH remain largely unexplored. OBJECTIVE: We sought to define the role of IL-13-induced transcriptional programs in esophageal epithelial proliferation in EoE. METHODS: We performed RNA sequencing, bioinformatics, Western blot, reverse transcriptase quantitative PCR, and histologic analyses on esophageal biopsies from healthy control and patients with EoE, primary esophageal cells derived from patients with EoE, and IL-13-stimulated esophageal epithelial keratinocytes grown at the air-liquid interface (EPC2-ALI). Genetic (shRNA) and pharmacologic (proteolysis-targeting chimera degrader) approaches and in vivo model of IL-13-induced esophageal epithelial remodeling (Krt5-rtTA x tetO-IL-13Tg) were used to define the role of signal transducer and activator of transcription 3 (STAT3) and STAT6 and secreted frizzled-related protein 1 (SFRP1) in esophageal epithelial proliferation. RESULTS: RNA-sequencing analysis of esophageal biopsies (healthy control vs EoE) and EPC2-ALI revealed 82 common differentially expressed genes that were enriched for putative STAT3 target genes. In vitro and in vivo analyses revealed a link between IL-13-induced STAT3 and STAT6 phosphorylation, SFRP1 mRNA expression, and esophageal epithelial proliferation. In vitro studies showed that IL-13-induced esophageal epithelial proliferation was STAT3-dependent and regulated by the STAT3 target SFRP1. SFRP1 mRNA is increased in esophageal biopsies from patients with active EoE compared with healthy controls or patients in remission and identifies an esophageal suprabasal epithelial cell subpopulation that uniquely expressed the core EoE proinflammatory transcriptome genes (CCL26, ALOX15, CAPN14, ANO1, and TNFAIP6). CONCLUSIONS: These studies identify SFRP1 as a key regulator of IL-13-induced and STAT3-dependent esophageal proliferation and BZH in EoE and link SFRP1+ esophageal epithelial cells with the proinflammatory and epithelial remodeling response in EoE.

MMP9 and TYROBP affect the survival of circulating tumor cells in clear cell renal cell carcinoma by adapting to tumor immune microenvironment.

Circulating tumor cells (CTCs) play a key role in tumor metastasis. CTCs have altered gene expression and can survive in the bloodstream. Finding the key genes whose expression are altered in CTCs could help explain the mechanism of tumor metastasis. We searched for genes differentially expressed in CTCs by analyzing four CTCs and primary tumor gene expression datasets in the GEO database. Key genes of clear cell renal cell carcinoma (ccRCC) CTCs were identified. The correlation between key genes and the immune microenvironment of ccRCC was explored. Finally, the CTCs cell model of ccRCC was constructed by in vivo screening method, and the expression of key genes was detected at the cell and tissue levels. A total of 771 DEGs were obtained. Gene enrichment analysis showed that DEGs of CTCs were mainly involved in the regulation of the tumor immune process and tumor cell apoptosis. Finally, we found 2 key genes, MMP9 and TYROBP in ccRCC CTCs. The high expression of these 2 genes predicted a poor prognosis of ccRCC, and the expression levels of these 2 genes were significantly increased in CTCs and ccRCC tissues. Our study suggested that genetic alterations in CTCs contribute to the ability of CTCs to survive in the blood by adapting to the tumor microenvironment. MMP9 and TYROBP are potential therapeutic and prognostic targets for ccRCC.

High oil content inhibits humification in food waste composting by affecting microbial community succession and organic matter degradation.

Composting is an effective technology to realize resource utilization of food waste in rural China. However, high oil content in food waste limits composting humification. This study investigated the effects of blended plant oil addition at different proportions (0, 10, 20, and 30%) on the humification of food waste composting. Oil addition at 10%-20% enhanced lignocellulose degradation by 16.6%-20.8% and promoted humus formation. In contrast, the high proportion of oil (30%) decreased the pH, increased the electrical conductivity, and reduced the seed germination index to 64.9%. High-throughput sequencing showed that high oil inhibited the growth and reproduction of bacteria (Bacillus, Fodinicurvataceae, and Methylococcaceae) and fungi (Aspergillus), attenuated their interaction, thus, reducing the conversion of organic matter, such as lignocellulose, fat, and total sugar, to humus, consequently leading to negative impacts on composting humification. The results can guide composting parameter optimization and improve effective management of rural food waste.

Mid-term study on the effects of arthroscopic discoid lateral meniscus plasty on patellofemoral joint: An observational study.

In the present study, we aimed to investigate the clinical outcomes of arthroscopic discoid lateral meniscus (DLM) plasty and the adaptive changes in the patellofemoral joint after surgery. From September 2010 to March 2012, 25 patients with DLM injuries who underwent arthroscopic meniscus plasty were enrolled in the prospective study. All patients underwent clinical evaluation before the operation and at the last follow-up, and imaging evaluation was performed by upright magnetic resonance imaging before and 1 month after the operation as well as at the last follow-up. Clinical evaluation included Lysholm score, Kujala score, McMurray's sign, patellar mobility, patella grind test, and quadriceps atrophy. Imaging evaluation included bisect offset index, patella tilt angle (PTA), and cartilage damage. Lysholm score, Kujala score, McMurray's sign, and quadriceps atrophy at the last follow-up were significantly improved compared with the preoperative levels (P < .05). At the last follow-up, there were no statistical differences in patella mobility and patella grind test compared with the preoperative levels. In addition, bisect offset index and PTA showed a dynamic trend of rising and then falling over time (P < .05). At 1 month after the operation, bisect offset index and PTA were significantly increased compared with the preoperative levels or the values at the last follow-up (P < .05), while there were no differences between the preoperation and the last follow-up. Cartilage damage became worse with time (P < 0.05), and the 2 were positively correlated (Spearman = 0.368). At the last follow-up, the degree of cartilage damage was significantly increased compared with the preoperative level (P < .017), while there was no significant difference between the 1-month postoperative grade and the preoperational grade or the last follow-up grade. The effect of arthroscopic DLM plasty on the patellofemoral joint was dynamic, with the position of the patella deviating in the early stages and recovering in the mid-term, especially when the knee was in the biomechanical standing position. In addition, the patellofemoral joint cartilage might undergo accelerated degeneration after the operation, while the mid-term effect of the operation was positive, and the patellofemoral joint function was acceptable.

Identification of risk factors for 1-year mortality among critically ill older adults with hip fractures surgery: A single medical center retrospective study.

Aim: The purpose of this study was to analyze the potential risk factors for mortality 1 year after hip fracture surgery in critically ill older adults. Methods: We reviewed 591 critically ill older adults who underwent hip surgery at our institution from January 2018 to April 2021. We collected baseline demographics, clinical information, and 1-year survival status of the sample patients by means of medical record systems and follow-up phone calls. Patients were divided into survival and mortality groups based on survival within 1 year after surgery. Results: Based on the results of the 1-year postoperative follow-up of patients, we obtained 117 cases in the death group and 474 cases in the survival group, and this led to a 1-year mortality rate of 19.8% (117/591) after hip fracture in critically ill older adults at our hospital. The risk factors that influenced the 1-year postoperative mortality were identified as advanced age (HR:1.04, 95%, 1.01-1.06), preoperative arrhythmia (HR: 1.95, 95%, 1.26-2.70), high level of NLR (HR:1.03, 95%, 1.01-1.06), respiratory failure (HR: 2.63, 95%, 1.32-5.23), and acute cardiovascular failure. 5.23) and acute cardiovascular events (HR: 1.65, 95%, 1.05-2.59). Conclusion: Advanced age, preoperative arrhythmias, high levels of NLR, postoperative respiratory failure, and acute cardiovascular events were independent risk factors for survival of critically ill older adults with hip fracture at 1 year after surgery. Therefore, laboratory tests such as high levels of preoperative NLR can be an important indicator of patient prognosis.

Corrigendum: A New Prognostic Risk Score: Based on the Analysis of Autophagy-Related Genes and Renal Cell Carcinoma.

[This corrects the article DOI: 10.3389/fgene.2021.820154.].

Four-octyl itaconate improves osteoarthritis by enhancing autophagy in chondrocytes via PI3K/AKT/mTOR signalling pathway inhibition.

Osteoarthritis (OA) is a highly prevalent and chronic disorder that is associated with a substantial social and economic burden. Itaconate, as an important regulator of cellular inflammation, is a metabolite synthesised by an enzyme encoded by immune-responsive gene 1. However, there are few studys regarding the effects of itaconate on OA. Here, we show the effect of the cell-permeable itaconate derivative 4-octyl itaconate (OI) on OA. OI attenuates the chondrocyte apoptosis induced by interleukin 1ß (IL-1ß) in vitro, indicating that OI protect chondrocytes against apoptosis. Moreover, OI ameliorates the chondrocyte autophagy inhibition induced by IL-1ß via the inhibition of PI3K/AKT/mTOR signalling pathway. Finally, OI enhances autophagy and reduces cartilage degradation in a rat model of OA established by destabilization of medial meniscus (DMM). In summary, our findings reveal that OI is involved in regulating the progression of OA. The above results shed light on the treatment of OA.

HDAC inhibitor quisinostat prevents estrogen deficiency-induced bone loss by suppressing bone resorption and promoting bone formation in mice.

Postmenopausal osteoporosis (PMOP) is a metabolic skeletal disorder characterized by reduced bone mass and impaired bone microarchitecture resulting in increased bone fragility and fracture risk. PMOP is primarily caused by excessive osteoclastogenesis induced by estrogen deficiency. Quisinostat (Qst) is a potent hydroxamate-based second-generation inhibitor of histone deacetylases (HDACs) that can inhibit osteoclast differentiation in vitro, and protect mice from titanium particle-induced osteolysis in vivo. However, whether Qst has therapeutic potential against PMOP remains unclear. In the present study, we evaluated the therapeutic efficacy of Qst on PMOP, using a murine model of ovariectomy (OVX)-induced osteoporosis. We examined the body weight, femur length, and histology of major organs, and showed that Qst did not cause obvious toxicity in mice. Micro-computed tomography and histological analyses revealed that Qst treatment prevented OVX-induced trabecular bone loss both in femurs and vertebrae. Moreover, ELISA showed that Qst decreased the serum levels of the osteoclastic bone resorption marker CTX-1, whereas increased the levels of the osteoblastic bone formation marker Osteocalcin in OVX mice. Consistent with the CTX-1 results, TRAP staining showed that Qst suppressed OVX-induced osteoclastogenesis. Mechanistically, we showed that Qst suppressed RANKL-induced osteoclast differentiation in part by inhibiting p65 nuclear translocation. Collectively, our results demonstrated that Qst can ameliorate estrogen deficiency-induced osteoporosis by inhibiting bone resorption and promoting bone formation in vivo. In summary, our study provided the first preclinical evidence to support Qst as a potential therapeutic agent for PMOP prevention and treatment.

Abnormal expression and the significant prognostic value of aquaporins in clear cell renal cell carcinoma.

Aquaporins (AQPs) are a kind of transmembrane proteins that exist in various organs of the human body. AQPs play an important role in regulating water transport, lipid metabolism and glycolysis of cells. Clear cell renal cell carcinoma (ccRCC) is a common malignant tumor of the kidney, and the prognosis is worse than other types of renal cell cancer (RCC). The impact of AQPs on the prognosis of ccRCC and the potential relationship between AQPs and the occurrence and development of ccRCC are demanded to be investigated. In this study, we first explored the expression pattern of AQPs by using Oncomine, UALCAN, and HPA databases. Secondly, we constructed protein-protein interaction (PPI) network and performed function enrichment analysis through STRING, GeneMANIA, and Metascape. Then a comprehensive analysis of the genetic mutant frequency of AQPs in ccRCC was carried out using the cBioPortal database. In addition, we also analyzed the main enriched biological functions of AQPs and the correlation with seven main immune cells. Finally, we confirmed the prognostic value of AQPs throughGEPIA and Cox regression analysis. We found that the mRNA expression levels of AQP0/8/9/10 were up-regulated in patients with ccRCC, while those of AQP1/2/3/4/5/6/7/11 showed the opposite. Among them, the expression differences of AQP1/2/3/4/5/6/7/8/9/11 were statistically significant. The differences in protein expression levels of AQP1/2/3/4/5/6 in ccRCC and normal renal tissues were consistent with the change trends of mRNA. The biological functions of AQPs were mainly concentrated in water transport, homeostasis maintenance, glycerol transport, and intracellular movement of sugar transporters. The high mRNA expression levels of AQP0/8/9 were significantly correlated with worse overall survival (OS), while those of AQP1/4/7 were correlated with better OS. AQP0/1/4/9 were prognostic-related factors, and AQP1/9 were independent prognostic factors. In general, this research has investigated the values of AQPs in ccRCC, which could become new survival markers for ccRCC targeted therapy.

A comprehensive assessment on bioavailability, leaching characteristics and potential risk of polycyclic aromatic hydrocarbons in biochars produced by a continuous pyrolysis system.

Biochar application as a soil amendment has attracted worldwide attention. Nevertheless, polycyclic aromatic hydrocarbons (PAHs) formed during biochar production might enter into ecosystems and threaten human health after application to soil. Continuous pyrolysis systems tend to cause an accumulation of PAHs in biochar owing to short residence time and rapid cooling. This study conducted a comprehensive assessment regarding potential risk of PAHs in biochars produced by a continuous pyrolysis system based on bioavailability, leaching behavior, toxic equivalent quantity, health risk and phytotoxicity of PAHs. Results showed that the concentrations of total PAHs in biochars were in the range of 93.40-172.40 mg/kg, exceeding the European Biochar Certificate standard. 3-rings PAHs were the predominant groups. The percentages of total freely dissolved and leachable PAHs were lower than 1%. RH contained the least bioavailable and leachable PAHs concentration and phytotoxicity compared with CS and PS, which might attribute to the characteristic of three biochars. CS and PS were acidic and exhibited high levels of DOC and VFAs, while RH was strongly alkaline and presented greater aromaticity and higher surface area, which might have resulted in high adsorptive capacity and decreased bioavailability of PAHs. When the biochar application rate was higher than 0.6 t/ha, the incremental lifetime cancer risk value for human exposure to biochar-borne PAHs through the biochar-amended soil was over 10-6, suggesting carcinogenic risks. Germination index values of biochars ranged from 25.66 to 88.95%. Phytotoxicity mainly was caused by bioavailable PAHs and dissolved organic compounds. Overall, these findings highlighted that although the percentage of bioavailable PAHs was low, the potential health risk and phytotoxicity of PAHs in biochars produced by a continuous pyrolysis system was of a great concern. High biochar application rates should be avoided without processing both for soil safety and human health.

SD-91 as A Potent and Selective STAT3 Degrader Capable of Achieving Complete and Long-Lasting Tumor Regression.

Signal transducer and activator of transcription 3 (STAT3) is an attractive cancer therapeutic target. We report herein our extensive in vitro and in vivo evaluations of SD-91, the product of the hydrolysis of our previously reported STAT3 degrader SD-36. SD-91 binds to STAT3 protein with a high affinity and displays >300-fold selectivity over other STAT family protein members. SD-91 potently and effectively induces degradation of STAT3 protein and displays a high selectivity over other STAT members and >7000 non-STAT proteins in cells. A single administration of SD-91 selectively depletes STAT3 protein in tumor tissues with a persistent effect. SD-91 achieves complete and long-lasting tumor regression in the MOLM-16 xenograft model in mice even with weekly administration. Hence, SD-91 is a potent, highly selective, and efficacious STAT3 degrader for extensive evaluations for the treatment of human cancers and other diseases for which STAT3 plays a key role.

Comparison of the TightRope system versus hook plate in acute acromioclavicular joint dislocations: a retrospective analysis.

This study compared the results of the minimally invasive coracoclavicular (CC) fixation with a single TightRope (MITR) procedure and the hook plate (HP) procedure for acute acromioclavicular (AC) joint dislocation treatment. Sixteen patients with a mean age of 44.9 ± 11 years were treated with the MITR procedure. Nineteen patients with a mean age of 40.2 ± 8.7 years were treated using the HP procedure. Clinical outcomes were evaluated with the Visual Analog Scale (VAS) for pain, Constant-Murley Score (CMS), and University of California at Los Angeles (UCLA) Shoulder score. Vertical displacement of the clavicle with reference to the height of the acromion was measured in standard anteroposterior radiographs. The mean follow-up was 27 months in the MITR group and 30 months in the HP group. No statistically significant differences were found between the MITR group and the HR group in terms of VAS score (0.4 ± 0.6 vs 0.7 ± 0.6, P = 0.138), UCLA Shoulder score (33.9 ± 2.5 vs 33.7 ± 1.5, P = 0.843), or CMS (95.7 ± 7.3 vs 93.7 ± 6.6, P = 0.400). No redislocation was identified in the HP group, while redislocation occurred in 1 of 16 (6.3%) patients in the MITR group. One patient in the HP group (5.3%) had acromial osteolysis, while no acromial osteolysis was found in the MITR group. No other adverse events, such as infections, tunnel widening, fractures, or implant-related complications, were observed. Both procedures provided satisfactory results. The HP procedure provided better reduction, while the MITR procedure provided a slightly lower tendency of pain. Long-term follow-up is needed to investigate the clinical outcomes and radiological outcomes of both groups.