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.

Assessment of urban flood resilience based on the socio-ecological composite index model: a case study in Wuhua District, Kunming City, China.

Global climate change and rapid urbanization have increased the frequency of flooding, making urban flood resilience a critical objective. This article introduces a methodology for assessing urban flood resilience, utilizing a social-ecological synthesis index that integrates geographical and temporal data with Geographic Information System (GIS). The study focuses on ten administrative subdistricts in Wuhua District, Kunming City, China, and selects 18 social-ecological indicators. These indicators, chosen from social and ecological perspectives, are weighted using the entropy weight method to determine their significance in the assessment system. By combining scores for each subdistrict, the study quantifies flood resilience and creates a spatial distribution map using ArcGIS. Key findings reveal that out of the ten administrative subdistricts, five in Wuhua District, particularly in the core urban area of Kunming, demonstrate strong overall flood resilience. Influenced by social-ecological indicators, there is significant spatial differentiation in flood resilience within Wuhua District, with a decreasing trend radiating from the city center to areas farther from the urban core. The research indicates that regions with well-established transportation infrastructure, a wide distribution of government institutions, improved water management facilities, and a substantial population with higher education levels contribute significantly to enhancing urban flood resilience.

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.

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-4-STAT6 axis amplifies histamine-induced vascular endothelial dysfunction and hypovolemic shock.

BACKGROUND: Mast cell-derived mediators induce vasodilatation and fluid extravasation, leading to cardiovascular failure in severe anaphylaxis. We previously revealed a synergistic interaction between the cytokine IL-4 and the mast cell-derived mediator histamine in modulating vascular endothelial (VE) dysfunction and severe anaphylaxis. The mechanism by which IL-4 exacerbates histamine-induced VE dysfunction and severe anaphylaxis is unknown. OBJECTIVE: We sought to identify the IL-4-induced molecular processes regulating the amplification of histamine-induced VE barrier dysfunction and the severity of IgE-mediated anaphylactic reactions. METHODS: RNA sequencing, Western blot, Ca2+ imaging, and barrier functional analyses were performed on the VE cell line (EA.hy926). Pharmacologic degraders (selective proteolysis-targeting chimera) and genetic (lentiviral short hairpin RNA) inhibitors were used to determine the roles of signal transducer and activator of transcription 3 (STAT3) and STAT6 in conjunction with in vivo model systems of histamine-induced hypovolemic shock. RESULTS: IL-4 enhancement of histamine-induced VE barrier dysfunction was associated with increased VE-cadherin degradation, intracellular calcium flux, and phosphorylated Src levels and required transcription and de novo protein synthesis. RNA sequencing analyses of IL-4-stimulated VE cells identified dysregulation of genes involved in cell proliferation, cell development, and cell growth, and transcription factor motif analyses revealed a significant enrichment of differential expressed genes with putative STAT3 and STAT6 motif. IL-4 stimulation in EA.hy926 cells induced both serine residue 727 and tyrosine residue 705 phosphorylation of STAT3. Genetic and pharmacologic ablation of VE STAT3 activity revealed a role for STAT3 in basal VE barrier function; however, IL-4 enhancement and histamine-induced VE barrier dysfunction was predominantly STAT3 independent. In contrast, IL-4 enhancement and histamine-induced VE barrier dysfunction was STAT6 dependent. Consistent with this finding, pharmacologic knockdown of STAT6 abrogated IL-4-mediated amplification of histamine-induced hypovolemia. CONCLUSIONS: These studies unveil a novel role of the IL-4/STAT6 signaling axis in the priming of VE cells predisposing to exacerbation of histamine-induced anaphylaxis.

A Scoping Review of the Epidemiology, Management, and Outcomes of Golf-Related Fractures.

ABSTRACT: Golf is a popular sport; however, there is a paucity of data in relation to golf-associated fractures, and the rate and timing of returning to golf. The aim of this review is to describe golf-associated fractures, including epidemiology, management, and timing of returning to golf following treatment. A literature search was performed using MEDLINE/PubMed, Embase, and Web of Science. Data were extracted and summarized in a narrative synthesis. A total of 436 articles were identified with an initial search of which 58 met the inclusion criteria. Twelve anatomical sites of golf swing-related fractures were identified, of which 10 sites were specific for stress fractures. The most common sites of golf swing-related stress fractures were the ribs followed by the hook of hamate. There was a common theme of delay to diagnosis, being initially assigned to a soft tissue injury. Most golfers with swing-related stress fractures were able to return to golf with the exception of osteoporotic associated vertebral stress fractures. Timing of returning to golf was between 4 and 12 months for most of the golfers with stress fractures following conservative management. Operative intervention was an option of hook of hamate nonunion, following a stress fracture, and tibial shaft stress fractures. Golf equipment-related fractures were not rare and were associated with major trauma and in some cases associated with significant persistent morbidity. Golf-related stress fractures commonly involve the ribs and hook of hamate; knowledge of this may aid in early diagnosis and appropriate treatment when symptomatic golfers are encountered. Although golf is a noncontact sport, fractures associated with golf equipment can be life changing, and safety training guidelines should be established.

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.

Biomechanical study of different bone cement distribution on osteoporotic vertebral compression Fracture-A finite element analysis.

Purpose: This study aimed to compare the biomechanical effects of different bone cement distribution methods on osteoporotic vertebral compression fractures (OVCF). Patients and methods: Raw CT data from a healthy male volunteer was used to create a finite element model of the T12-L2 vertebra using finite element software. A compression fracture was simulated in the L1 vertebra, and two forms of bone cement dispersion (integration group, IG, and separation group, SG) were also simulated. Six types of loading (flexion, extension, left/right bending, and left/right rotation) were applied to the models, and the stress distribution in the vertebra and intervertebral discs was observed. Additionally, the maximum displacement of the L1 vertebra was evaluated. Results: Bone cement injection significantly reduced stress following L1 vertebral fractures. In the L1 vertebral body, the maximum stress of SG was lower than that of IG during flexion, left/right bending, and left/right rotation. In the T12 vertebral body, compared with IG, the maximum stress of SG decreased during flexion and right rotation. In the L2 vertebral body, the maximum stress of SG was the lowest under all loading conditions. In the T12-L1 intervertebral disc, compared with IG, the maximum stress of SG decreased during flexion, extension, and left/right bending and was basically the same during left/right rotation. However, in the L1-L2 intervertebral discs, the maximum stress of SG increased during left/right rotation compared with that of IG. Furthermore, the maximum displacement of SG was smaller than that of IG in the L1 vertebral bodies under all loading conditions. Conclusions: SG can reduce the maximum stress in the vertebra and intervertebral discs, offering better biomechanical performance and improved stability than IG.

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.

Research Progress on Surface Damage and Protection Strategies of Armature-Rail Friction Pair Materials for Electromagnetic Rail Launch.

Electromagnetic rail launch technology has attracted increasing attention owing to its advantages in terms of range, firepower, and speed. However, due to electricity-magnetism-heat-force coupling, the surface of the armature-rail friction pair becomes severely damaged, which restricts the development of this technology. A series of studies have been conducted to reduce the damage of the armature-rail friction pair, including an analysis of the damage mechanism and protection strategies. In this study, various types of surface damage were classified into mechanical, electrical, and coupling damages according to their causes. This damage is caused by factors such as mechanical friction, mechanical impact, and electric erosion, either individually or in combination. Then, a detailed investigation of protection strategies for reducing damage is introduced, including material improvement through the use of novel combined deformation and heat treatment processes to achieve high strength and high conductivity, as well as surface treatment technologies such as structural coatings for wear resistance and functional coatings for ablation and melting resistance. Finally, future development prospects of armature-rail friction pair materials are discussed. This study provides a theoretical basis and directions for the development of high-performance materials for the armature-rail friction pair.

Study of the variation law of the airflow resistance and related physical parameters of the pile throughout compost process with cattle manure.

Composting is widely adopted in livestock waste management, and the ventilation system control is essential for composting efficiency. For ventilation system, the airflow resistance is a major factor influencing the ventilation intensity and oxygen supply capacity. This study explored the variation law of airflow resistance, bulk density, specific gravity, particle size and total pressure throughout composting with cattle manure. The airflow resistance was calculated with Ergun equation, and contribution coefficients of different components were analyzed with principal component analysis (PCA). Results showed that the viscous airflow resistance was dominant throughout cattle manure composting. The average airflow resistance was 0.146 Pa/m, and resistance of pile at lower layer was higher than that at the upper layer by 18.1 %. For contribution coefficient affecting airflow resistance, the ranks were bulk density, average particle size and specific gravity. During composting process, the average airflow resistance decreased by 40.1 % and the total pressure reduced by 3.47 %. All parameters had the greatest variation at thermophilic phase, which accounted for more than 60 % of the total variation amplitude. Meanwhile, less than 10 % of the total pressure was used to overcome the airflow resistance. Therefore, reducing bulk density of pile should be considered preferentially to decrease the airflow resistance. During cattle manure composting process, the total pressure of ventilation system ought to be adjusted with the aerobic reaction to a lower level, especially at thermophilic phase with the most rapid descent rate. This study can provide support for reducing the energy consumption required for ventilation of composting.

Biochar addition accelerates the humification process by affecting the microbial community during human excreta composting.

Biochar addition plays an important role in manure composting, but its driving mechanism on microbial succession and humification process of human excreta composting is still unclear. In the present study, the mechanism of biochar addition was explored by analysing the humification process and microbial succession pattern of human excreta aerobic composting without and with 10% biochar (HF and BHF). Results indicated that BHF improved composting temperature, advanced the thermophilic phase by 1 d, increased the germination index by 49.03%, promoted the growth rate of humic acid content by 17.46%, and raised the compost product with the ratio of humic acid to fulvic acid (HA/FA) by 16.19%. Biochar regulated the diversity of fungi and bacteria, increasing the relative abundance of Planifilum, Meyerozyma and Melanocarpus in the thermophilic phase, and Saccharomonospora, Flavobacterium, Thermomyces and Remersonia in the mature phase, which accelerates the humification. Bacterial communities' succession had an obvious correlation with the total carbon, total nitrogen, and temperature (P < 0.05), while the succession of fungal communities was influenced by the HA/FA and pH (P < 0.05). This study could provide a reference for the improvement of on-site human excreta harmless by extending the thermophilic phase, and facilitating the humification in human excreta compost with biochar addition.

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.

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.

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.

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.

A novel homozygous C-terminal deletion in BTG4 causes zygotic cleavage failure and female infertility.

PURPOSE: We aimed to identify pathogenic variants in a female patient with primary infertility and recurrent failure of in vitro fertilization with zygotic cleavage failure. METHODS: The genomic DNA from the affected individual was subjected to whole-exome sequencing and the variant was confirmed by Sanger sequencing. The functional effect of the identified variant was further investigated in 293 T cells. RESULTS: We identified a novel homozygous deletion in BTG4 (c.580_616del) in the affected individual. The deletion results in frameshift and replacement of the last 29 residues (aa195-223) with 66 random amino acids. The mutated amino acid residues are highly conserved among mammalian species. Co-immunoprecipitation in 293 T cells showed that the mutation abolished the interaction between BTG4 and PABPN1L. CONCLUSION: This study conforms previous studies and expands the mutational spectrum of BTG4. Our findings prove the functional importance of the C-terminal of BTG4. BTG4 is a potential diagnostic and therapeutic target for patients suffering from zygotic cleavage failure.