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Abstract Background Breast cancer is the most prevalent cancer in women globally. Over-activated estrogen receptor (ER) α signaling is considered the main factor in luminal breast cancers, which can be effectively managed with selective estrogen receptor modulators (SERMs) like tamoxifen. However, approximately 30–40% of ER + breast cancer cases are recurrent after tamoxifen therapy. This implies that the treatment of breast cancer is still hindered by resistance to tamoxifen. Recent studies have suggested that post-translational modifications of ERα play a significant role in endocrine resistance. The stability of both ERα protein and its transcriptome is regulated by a balance between E3 ubiquitin ligases and deubiquitinases. According to the current knowledge, approximately 100 deubiquitinases are encoded in the human genome, but it remains unclear which deubiquitinases play a critical role in estrogen signaling and endocrine resistance. Thus, decoding the key deubiquitinases that significantly impact estrogen signaling, including the control of ERα expression and stability, is critical for the improvement of breast cancer therapeutics. Methods We used several ER positive breast cancer cell lines, DUB siRNA library screening, xenograft models, endocrine-resistant (ERα-Y537S) model and performed immunoblotting, real time PCR, RNA sequencing, immunofluorescence, and luciferase activity assay to investigate the function of USP36 in breast cancer progression and tamoxifen resistance. Results In this study, we identify Ubiquitin-specific peptidase 36 (USP36) as a key deubiquitinase involved in ERα signaling and the advancement of breast cancer by deubiquitinases siRNA library screening. In vitro and in vivo studies showed that USP36, but not its catalytically inactive mutant (C131A), could promote breast cancer progression through ERα signaling. Conversely, silencing USP36 inhibited tumorigenesis. In models resistant to endocrine therapy, silencing USP36 destabilized the resistant form of ERα (Y537S) and restored sensitivity to tamoxifen. Molecular studies indicated that USP36 inhibited K48-linked polyubiquitination of ERα and enhanced the ERα transcriptome. It is interesting to note that our results suggest USP36 as a novel biomarker for treatment of breast cancer. Conclusion Our study revealed the possibility that inhibiting USP36 combined with tamoxifen could provide a potential therapy for breast cancer.

Abstract Purpose To confirm which method provides lower rate of recurrent instability and superior clinical outcomes. Method We searched PubMed, Embase and Web of Science for the trials involving one intervention or both for patellar instability: medial patellofemoral ligament reconstruction (MPFLR) with and without tibial tubercle osteotomy (TTO). The postoperative Kujala score, Lysholm score, Tegner scores and the rate of recurrent instability (dislocation or subluxation) were analyzed as the primary clinical outcome parameters in a random or fixed effects meta-analysis. Results In total, 43 articles met inclusion criteria after full-text review. A total of 2046 patients were analyzed. The overall mean age was 20.3 years (range, 9.5–60.0 years), with a mean follow-up time of 3.2 years (range, 1–8 years). The mean Kujala scores in MPFLR and MPFLR + TTO were 89.04 and 84.44, respectively. There was significant difference in Kujala scores between MPFLR and MPFLR + TTO (MD = 4.60, 95%CI: 1.07–8.13; P = 0.01). The mean Lysholm scores in MPFLR and MPFLR + TTO were 90.59 and 88.14, respectively. There was no significant difference in Lysholm scores between MPFLR and MPFLR + TTO (MD = 2.45, 95%CI: -3.20-8.10; P = 0.40). The mean Tegner scores in MPFLR and MPFLR + TTO were 5.30 and 4.88, respectively. There was no significant difference in Tegner scores between MPFLR and MPFLR + TTO (MD = 0.42, 95%CI: -0.39-1.23; P = 0.31). At final follow-up, the rates of recurrent instability in MPFLR and MPFLR + TTO were 3% and 4%, respectively. There was no significant difference in the rates between MPFLR and MPFLR + TTO (OR = 0.99, 95%CI: 0.96–1.02; P = 0.4848). Conclusion MPFLR and MPFLR + TTO are effective and reliable treatments in the setting of patellofemoral instability. MPFLR seems to show a better performance in functional outcomes than MPFLR + TTO. Moreover, their rates of recurrent instability are very low, and no significant difference exists.

Abstract Colon cancer is a prevalent malignancy, while recent studies revealed the dys-regulation of Hippo signaling as the important driver for colon cancer progression. Several studies have indicated that post-translational modifications on YAP play crucial roles in both Hippo signaling activity and cancer progression. This raises a puzzling question about why YAP/TAZ, an auto-inhibitory pathway, is frequently over-activated in colon cancer, despite the suppressive cascade of Hippo signaling remaining operational. The protein stability of YAP is subject to a tiny balance between ubiquitination and deubiquitination processes. Through correlation analysis of DUBs (deubiquitinases) expression and Hippo target gene signature in colon cancer samples, we found JOSD1 as a critical deubiquitinase for Hippo signaling and colon cancer progression. JOSD1 could facilitate colon cancer progression and in colon cancer, inhibition of JOSD1 via shRNA has been demonstrated to impede tumorigenesis. Furthermore, molecular mechanism studies have elucidated that JOSD1 enhances the formation of the Hippo/YAP transcriptome by impeding K48-linked polyubiquitination on YAP. ChIP assays have shown that YAP binds to JOSD1’s promoter region, promoting its gene transcription. These results suggest that JOSD1 is involved in both activating and being targeted by the Hippo signaling pathway in colon cancer. Consequently, a positive regulatory loop between JOSD1 and Hippo signaling has been identified, underscoring their interdependence during colon cancer progression. Thus, targeting JOSD1 may represent a promising therapeutic approach for managing colon cancer.

Abstract Tropical cyclones (TCs) and their associated intense rainfall are among the most significant natural disasters. Exploring the characteristics of tropical cyclone precipitation (TCP) has always been a challenging issue in TC research. This study utilized the TC track data from the International Best Track Archive for Climate Stewardship and precipitation data from the multi-source weighted-ensemble precipitation covering the years 1980–2019, to examine shifts in precipitation rates and peak precipitation levels before and after TC landfall. The results highlight several key findings: (1) Precipitation during the TC landfall process is relatively stable beforehand but tends to decrease slightly after landfall. Generally, the maximum precipitation occurs during the landfall. (2) From 1980 to 2019, the rate of precipitation changes before landfall has significantly increased. Conversely, after the year 2000, the rate of precipitation changes after landfall has significantly decreased. (3) Over the past 40 years, while peak precipitation levels of landfalling TCs have remained relatively constant, the total precipitation has shown an increasing trend, particularly in regions like the main island of Hainan, southern Zhejiang, and Shanghai, which are characterized by high peak precipitation. The results help clarify the TC processes and provide reference points for parameter selection in regional TCP modeling.

Background: Cold environments pose serious threats on human health, with increased risk for myocardial infarction, stroke, frostbite, and hypothermia. Acquired cold acclimation is required to minimize cold-induced injures and to improve metabolic health. However, the underlying mechanisms remain to be fully elucidated. Objective: We aimed to identify critical amino acids involved in cold acclimation and unmask the regulatory mechanisms. Methods: A total of twenty male participants were recruited and followed up after 3 months’ natural cold exposure. Cold-induced vasodilation (CIVD) tests and clinical biochemical analysis were performed at baseline and after 3-months cold exposure, whilst blood samples were collected, and plasma amino acids were analyzed by targeted metabolomics. To further confirm the effect of lysine on cold tolerance and explain the latent mechanism, mice were challenged with chronic cold exposure for 7 days with lysine supplement, then core and local surface temperature as well as thermogenesis activity were detected. Results: Continuous cold exposure shortened the CIVD onset time and increased the average finger temperature. Levels of the plasma lysine and glycine were decreased in both humans and mice. Venn analysis from three datasets revealed that lysine was the only significantly changed plasma amino acid, which strongly correlated with the altered CIVD. Moreover, mice sustained a relatively higher core temperature and surface temperature in the back, tail and paws upon lysine supplementation. Furthermore, lysine supplementation increased the level of histone H3K18cr and promoted the gene and protein expression of Cpt1a, Cpt2 and Cyp27a1 in liver. Conclusion: Our work identified lysine as a critical amino acid for the remodeling of hepatic histone crotonylation that facilitates cold acclimation.

Amplifying small subunit (SSU) rRNA genes with universal primers in assessing microbial populations diversity, but target microorganisms are sometimes omitted due to inadequate primer coverage. Adding degenerate bases to primers can help, but existing methods are complex and time-consuming. This study introduces a user-friendly tool called “Degenerate primer 111” for adding degenerate bases to existing universal primers. By aligning one universal primer with one uncovered target microorganism’s SSU rRNA gene, this tool iteratively generates a new primer, maximizing coverage for the target microorganisms. The tool was used to modify eight pairs of universal primers (515F Parada–806R Apprill, S-D-Bact-0341-b-S-17/S-D-Bact-0785-a-A-21, OP_F114-KP_R013, 27F-1492R, 341F-806R, OP_F066-KP_R013, 515F Parada–926R Quince, 616*F-1132R), and generated 29 new universal primers with increased coverage of specific target microorganisms without increasing coverage of non-target microorganisms. To verify the effectiveness of the improved primers, one set of original and improved primers (BA-515F-806R and BA-515F-806R-M1) was used to amplify DNA from the same sample, and high-throughput sequencing of the amplicons confirmed that the improved primers detected more microbial species compared to the original primers. Future researchers can use this tool to develop more personalized primers to meet their diverse microorganism detection needs.

Corrosion poses a significant threat to the structural integrity of steel rails, especially in an acidic environment. In this study, we evaluate the corrosion properties of U75V-welded joints using potentiodynamic polarization curves, electrochemical impedance measurements, and corrosion morphology studies under simulated acidic conditions. Compared to non-normalized joints, the normalized joints exhibit a higher self-corrosion current (4.65 × 10−5 A/cm2) and a more negative self-corrosion potential (−0.56919 mV). The smaller and more uniform grain size obtained after normalizing provides multiple active sites on the surface for polarization reactions. Furthermore, owing to significant erosion caused on the rail surface by the acidic solutions, normalizing treatment enhances the passivation effects on the surface, resulting in increased corrosion resistance (221.96 Ω cm2). Our findings provide insights into the impact of normalizing treatments on the corrosion mechanism of U75V rail joints under acidic conditions.

Abstract Somatic copy number alterations (SCNAs) are pervasive in advanced human cancers, but their prevalence and spatial distribution in early-stage, localized tumors and their surrounding normal tissues are poorly characterized. Here, we perform multi-region, single-cell DNA sequencing to characterize the SCNA landscape across tumor-rich and normal tissue in two male patients with localized prostate cancer. We identify two distinct karyotypes: ‘pseudo-diploid’ cells harboring few SCNAs and highly aneuploid cells. Pseudo-diploid cells form numerous small-sized subclones ranging from highly spatially localized to broadly spread subclones. In contrast, aneuploid cells do not form subclones and are detected throughout the prostate, including normal tissue regions. Highly localized pseudo-diploid subclones are confined within tumor-rich regions and carry deletions in multiple tumor-suppressor genes. Our study reveals that SCNAs are widespread in normal and tumor regions across the prostate in localized prostate cancer patients and suggests that a subset of pseudo-diploid cells drive tumorigenesis in the aging prostate.

Objective Surgical treatment with internal fixation, specifically percutaneous fixation with three cannulated compression screws (CCSs), is the preferred choice for young and middle‐aged patients. The mechanical advantage of the optimal spatial configuration with three screws provides maximum dispersion and cortical support. We suspect that the spatial proportion of the oblique triangle configuration (OTC) in the cross‐section of the femoral neck isthmus (FNI) may significantly improve shear and fatigue resistance of the fixed structure, thereby stabilizing the internal fixation system in femoral neck fracture (FNF). This study aims to explore the mechanical features of OTC and provide a mechanical basis for its clinical application. Methods Twenty Sawbone femurs were prepared as Pauwels type III FNF models and divided equally into two fixation groups: OTC and inverted equilateral triangle configuration (IETC). Three 7.3 mm diameter cannulated compression screws (CCSs) were used for fixation. The specimens of FNF after screw internal fixation were subjected to static loading and cyclic loading tests, respectively, with five specimens for each test. Axial stiffness, 5 mm failure load, ultimate load, shear displacement, and frontal rotational angle of two fragments were evaluated. In the cyclic loading test, the load sizes were 700 N, 1400 N, and 2100 N, respectively, and the fracture end displacement was recorded. Results were presented as means ± SD. Data with normal distributions were compared by the Student's t test. Results In the static loading test, the axial stiffness, ultimate load, shear displacement, and frontal rotational angle of two fragments were (738.64 vs. 620.74) N/mm, (2957.61 vs. 2643.06) N, (4.67 vs. 5.39) mm, and (4.01 vs. 5.52)° (p 0.05). Conclusion When three CCSs are inserted in parallel to fix FNF, the OTC of three screws has obvious biomechanical advantages, especially in shear resistance and early postoperative weight‐bearing, which provides a mechanical basis for clinical selection of ideal spatial configuration for unstable FNF.

BackgroundBladder cancer (BLCA) was recognized as a significant public health challenge due to its high incidence and mortality rates. The influence of molecular subtypes on treatment outcomes was well-acknowledged, necessitating further exploration of their characterization and application. This study was aimed at enhancing the understanding of BLCA by mapping its molecular heterogeneity and developing a robust prognostic model using single-cell and bulk RNA sequencing data. Additionally, immunological characteristics and personalized treatment strategies were investigated through the risk score.MethodsSingle-cell RNA sequencing (scRNA-seq) data from GSE135337 and bulk RNA-seq data from several sources, including GSE13507, GSE31684, GSE32894, GSE69795, and TCGA-BLCA, were utilized. Molecular subtypes, particularly the basal-squamous (Ba/Sq) subtype associated with poor prognosis, were identified. A prognostic model was constructed using LASSO and Cox regression analyses focused on genes linked with the Ba/Sq subtype. this model was validated across internal and external datasets to ensure predictive accuracy. High- and low-risk groups based on the risk score derived from TCGA-BLCA data were analyzed to examine their immune-related molecular profiles and treatment responses.ResultsSix molecular subtypes were identified, with the Ba/Sq subtype being consistently associated with poor prognosis. The prognostic model, based on basal-squamous subtype-related genes (BSSRGs), was shown to have strong predictive performance across diverse clinical settings with AUC values at 1, 3, and 5 years indicating robust predictability in training, testing, and entire datasets. Analysis of the different risk groups revealed distinct immune infiltration and microenvironments. Generally higher tumor mutation burden (TMB) scores and lower tumor immune dysfunction and exclusion (TIDE) scores were exhibited by the low-risk group, suggesting varied potentials for systemic drug response between the groups. Finally, significant differences in potential systemic drug response rates were also observed between risk groups.ConclusionsThe study introduced and validated a new prognostic model for BLCA based on BSSRGs, which was proven effective in prognosis prediction. The potential for personalized therapy, optimized by patient stratification and immune profiling, was highlighted by our risk score, aiming to improve treatment efficacy. This approach was promised to offer significant advancements in managing BLCA, tailoring treatments based on detailed molecular and immunological insights.

Summary: Emerging evidence highlights the regulatory role of paired-like (PRD-like) homeobox transcription factors (TFs) in embryonic genome activation (EGA). However, the majority of PRD-like genes are lost in rodents, thus prompting an investigation into PRD-like TFs in other mammals. Here, we showed that PRD-like TFs were transiently expressed during EGA in human, monkey, and porcine fertilized embryos, yet they exhibited inadequate expression in their cloned embryos. This study, using pig as the research model, identified LEUTX as a key PRD-like activator of porcine EGA through genomic profiling and found that LEUTX overexpression restored EGA failure and improved preimplantation development and cloning efficiency in porcine cloned embryos. Mechanistically, LEUTX opened EGA-related genomic regions and established histone acetylation via recruiting acetyltransferases p300 and KAT2A. These findings reveal the regulatory mechanism of LEUTX to govern EGA in pigs, which may provide valuable insights into the study of early embryo development for other non-rodent mammals.

Abstract As smartphones become increasingly prevalent worldwide, the relationship between smartphone addiction and subjective well-being has become a focal point in academic circles. Prior research predominantly delved into the direct correlation between smartphone addiction and subjective well-being, yet there remains a dearth in exploring its underlying mechanisms. This study investigated the mediating role of loneliness in the relationship between smartphone addiction and subjective well-being among Chinese university students. Conducted across 16 universities in eight provinces and municipalities in China, this study encompassed 1527 university students. Data collection utilized scales measuring smartphone addiction, loneliness, and subjective well-being. The findings revealed that: (1) demographic variables such as place of origin, educational level, and family income influenced university students' subjective well-being; (2) a significant negative correlation existed between smartphone addiction and subjective well-being among university students, coupled with a significant positive correlation between smartphone addiction and loneliness, indicating the significant negative predictive effect of smartphone addiction on subjective well-being; (3) loneliness partially mediated the relationship between smartphone addiction and subjective well-being among university students, suggesting that smartphone addiction could directly impact university students' subjective well-being, or indirectly through its effect on loneliness.

Abstract Background Identifying risk factors for adverse pathologic features in low-risk papillary thyroid microcarcinoma (PTMC) can provide valuable insights into the necessity of surgical or non-surgical treatment. This study aims to develop a nomogram for predicting the probability of adverse pathologic features in low-risk PTMC patients. Methods A total of 662 patients with low-risk PTMC who underwent thyroid surgery were retrospectively analyzed in Qilu Hospital of Shandong University from May 2019 to December 2021. Logistic regression analysis was used to determine the risk factors for adverse pathologic features, and a nomogram was constructed based on these factors. Results Most PTMC patients with these adverse pathologic features had tumor diameters greater than 0.6 cm (p 0.05 each). The nomogram was drawn to provide a quantitative and convenient tool for predicting the risk of adverse pathologic features based on age, gender, family history of thyroid cancer, autoimmune thyroiditis, tumor size, and BRAF V600E mutation in low-risk PTMC patients. The areas under curves (AUC) were 0.645 (95% CI 0.580–0.702). Additionally, decision curve analysis (DCA) and calibration curves were used to evaluate the clinical benefits of this nomogram, presenting a high net benefit. Conclusion Tumor size > 0.60 cm was identified as an independent risk factor for adverse pathologic features in low-risk PTMC patients. The nomogram had a high predictive value and consistency based on these factors.

Abstract Purpose To explore the effect of azvudine as compared to paxlovid for oral treatment of hospitalized patients with SARS-CoV-2 infection. Methods We analyzed data from a cohort of patients with SARS-CoV-2 infection in Shandong provincial hospital between February 15 and March 15, 2023. The primary outcome was time to sustained clinical recovery through Day 28 and secondary outcomes included the percentage of participants who died from any cause by Day 28, the average hospitilization time and expenses, the changes in liver and kidney function and adverse events. The Kaplan–Meier method and Cox regression model was used for statistical analysis. Results There was no significant difference between azvudine and paxlovid in terms of time to sustained clinical recovery (p = 0.429) and death rates (p = 0.687). As for hospitalization time and fee, no significant differences were observed between azvudine group and paxlovid group (Hospitalization time: p = 0.633; Hospitalization fee: p = 0.820). In addition, there were no significant differences in the effects of the two drugs on liver and kidney function (p > 0.05). Conclusion Among adults who were hospitalised with SARS-CoV-2 infection, azvudine was noninferior to paxlovid in terms of time to sustained clinical recovery, death rates, hospitalization time and cost, with few safety concerns. Trial registration ChiCTR2300071309; Registered 11 May 2023. Level of evidence Level III; Retrospective cohort study.

Abstract Objective This study aims to identify potential independent risk factors for residual low back pain (LBP) in patients with thoracolumbar osteoporotic vertebral compression fractures (OVCFs) following percutaneous kyphoplasty (PKP) treatment. Additionally, we aim to develop a nomogram that can accurately predict the occurrence of residual LBP. Methods We conducted a retrospective review of the medical records of thoracolumbar OVCFs patients who underwent PKP treatment at our hospital between July 2021 and December 2022. Residual LBP was defined as the presence of moderate or greater pain (VAS score ≥ 4) in the low back one day after surgery, and patients were divided into two groups: the LBP group and the non-LBP group. These patients were then randomly allocated to either a training or a validation set in the ratio of 7:3. To identify potential risk factors for residual LBP, we employed lasso regression for multivariate analysis, and from this, we constructed a nomogram. Subsequently, the predictive accuracy and practical clinical application of the nomogram were evaluated through a receiver operating characteristic (ROC) curve, a calibration curve, and a decision curve analysis (DCA). Results Our predictive model revealed that five variables—posterior fascial oedema, intravertebral vacuum cleft, time from fracture to surgery, sarcopenia, and interspinous ligament degeneration—were correlated with the presence of residual LBP. In the training set, the area under the ROC was 0.844 (95% CI 0.772–0.917), and in the validation set, it was 0.842 (95% CI 0.744–0.940), indicating that the model demonstrated strong discriminative performance. Furthermore, the predictions closely matched actual observations in both the training and validation sets. The decision curve analysis (DCA) curve suggested that the model provides a substantial net clinical benefit. Conclusions We have created a novel numerical model capable of accurately predicting the potential risk factors associated with the occurrence of residual LBP following PKP in thoracolumbar OVCFs patients. This model serves as a valuable tool for guiding specific clinical decisions for patients with OVCFs.

Abstract Background Duplication of the bladder with duplication of the posterior urethra is a relatively rare congenital malformation. Cases of sagittal septum duplication of the bladder with duplication of the posterior urethra have rarely been reported. Furthermore, the combination thereof with congenital megacolon is rare. Case presentation A 21-year-old male was admitted to our hospital because of frequent urination for two months. He presented to another hospital first with frequent urination and underwent computed tomography (CT) and testicular biopsy. Anti-inflammatory therapy was administered by the doctor to the patient. For further diagnosis and treatment, the patient went to the outpatient department in our hospital on June 6, 2022. After admission, the patient underwent ultrasound, CT, MRI, cystoscopy, and other related examinations and tests. The examination results suggested that the patient had duplication of the bladder with duplication of the posterior urethra. In addition, the patient’s mother reported that he had suffered from long-term constipation with abdominal distension before the age of 5 years. At the time, he was admitted to the local hospital and was diagnosed with congenital megacolon based on the relevant examinations. After the patient was diagnosed with duplication of bladder and urethra, the doctor recommended surgical treatment to the patient. However, he considered that he only had frequent urination symptoms, and chose conservative treatment rather than to undergo surgical treatment. Thus, the doctor prescribed anti-inflammatory treatment. Four months later, the patient reported that frequent urination symptoms persisted, and was also considering fertility-related problems. The outpatient follow-up will be continued. Conclusions In this article, we summarize the imaging findings of duplication of the bladder with duplication of the posterior urethra and propose the advantages and disadvantages of each type of imaging examination. We also review the relevant literature on cases of bladders with duplication of the posterior urethra. The related differential diagnosis is summarized, and the significance of guiding clinical treatment and diagnosis is discussed.

The complexity of petroleum phases in deep formations plays an important role in the evaluation of hydrocarbon resources. Pressure is considered to have a positive impact on the preservation of liquid oils, yet direct evidence for this phenomenon is lacking in the case of deep reservoirs due to late destruction. Here, we present fluid-inclusion assemblages from a deep reservoir in the Tazhong area of the Tarim Basin, northwestern China, which formed as a direct consequence of fluid pressure evolution. Based on thermodynamic measurements and simulations of the coexisting aqueous and petroleum inclusions in these assemblages, the history of petroleum activities was reconstructed. Our results show that all analyzed fluid-inclusion assemblages demonstrated variable pressure conditions in different charging stages, ranging from hydrostatic to overpressure (a pressure coefficient of up to 1.49). Sequential petroleum charging and partial oil cracking may have been the main contributors to overpressure. By comparing the phases of petroleum and fluid pressures in the two wells, ZS1 and ZS5, it can be inferred that overpressure inhibits oil cracking. Thus, overpressure exerts an important influence on the preservation of liquid hydrocarbon under high temperatures. Furthermore, our results reveal that the exploration potential for liquid petroleum is considerable in the deep reservoirs of the Tarim Basin.

BackgroundThe long-term prognosis of patients with stable coronary artery disease (CAD) combined with orthostatic hypotension (OH) has rarely been reported. This research was designed to examine whether OH increases the risk of all-cause mortality and cardiovascular death among patients with stable CAD.MethodsWe retrospectively analyzed retired military personnel over 65 years of age who were hospitalized at the General Hospital of Southern Theater Command of the Chinese People’s Liberation Army between March and July 2010. A total of 924 patients with stable CAD were included, among whom 263 had OH. The risk of all-cause mortality and cardiovascular death in OH and non-OH groups were analyzed with the Cox proportional hazards models, and restricted cubic spline plots were utilized for subgroup analyses. Furthermore, competing risk models were applied for sensitivity analyses.ResultsThe median age of the patients was 82.00 (80.00–85.00) years. Over 159 months of follow-up, the loss to follow-up rate was 2.27%, and all-cause mortality was observed in 574 (63.57%) patients, including 184 with OH. Moreover, cardiovascular death occurred in 127 patients (13.73%), with 58 cases associated with OH. Although the relationship between OH and all-cause mortality was non-significant [body mass index (BMI)

BackgroundCXC chemokine receptor 4 (CXCR4) is associated with the progression and metastasis of numerous malignant tumors. However, its relationship with Gastroenteropancreatic Neuroendocrine Neoplasms Grade 3 (GEP-NENs G3) is unclear. The aim of this study was to characterize the expression of CXCR4 in GEP-NENS and to explore the clinical and prognostic value of CXCR4.MethodsThis study retrospectively collected clinical and pathological data from patients with GEP-NENs who receiving surgery in Qilu Hospital of Shandong University from January 2013 to April 2021, and obtained the overall survival of the patients based on follow-up. Immunohistochemistry (IHC) was performed on pathological paraffin sections to observe CXCR4 staining. Groups were made according to pathological findings. Kaplan-Meier (K-M) curve was used to evaluate prognosis. SPSS 26.0 was used for statistical analysis.Results100 GEP-NENs G3 patients were enrolled in this study. There was a significant difference in primary sites (P=0.002), Ki-67 index (P

SMARCA4-deficient tumors are gaining attention, and this type of tumor is highly malignant with a poor prognosis. The frequency of SMARCA4 deletion varies in different tumors. However, it has never been identified in the pancreas. A 67-year-old woman presented with upper abdominal pain lasting for half a month. Computed tomography indicated a space-occupying lesion in the head of the pancreas, considered a malignant tumor. Further Endoscopic ultrasound fine-needle aspiration was performed and reported as SMARCA4-deficient undifferentiated pancreatic tumor. The patient received no treatment and survived only two and a half months from diagnosis to death. We are the first to report SMARCA4-deficient pancreatic undifferentiated tumor in which this new tumor entity presents with poorer overall survival. We also summarized the advances of SMARCA4 in oncology and treatment.

Abstract Background The Hippo pathway is crucial in organ size control and tumorigenesis. Dysregulation of the Hippo/YAP axis is commonly observed in gastric cancer, while effective therapeutic targets for the Hippo/YAP axis are lacking. Identification of reliable drug targets and the underlying mechanisms that could inhibit the activity of the Hippo/YAP axis and gastric cancer progression is urgently needed. Methods We used several gastric cancer cell lines and xenograft models and performed immunoblotting, qPCR, and in vivo studies to investigate the function of CXCR7 in gastric cancer progression. Results In our current study, we demonstrate that the membrane receptor CXCR7 (C-X-C chemokine receptor 7) is an important modulator of the Hippo/YAP axis. The activation of CXCR7 could stimulate gastric cancer cell progression through the Hippo/YAP axis in vitro and in vivo, while pharmaceutical inhibition of CXCR7 via ACT-1004–1239 could block tumorigenesis in gastric cancer. Molecular studies revealed that the activation of CXCR7 could dephosphorylate YAP and facilitate YAP nuclear accumulation and transcriptional activation in gastric cancer. CXCR7 functions via G-protein Gαq/11 and Rho GTPase to activate YAP activity. Interestingly, ChIP assays showed that YAP could bind to the promoter region of CXCR7 and facilitate its gene transcription, which indicates that CXCR7 is both the upstream signalling and downstream target of the Hippo/YAP axis in gastric cancer. Conclusion In general, we identified a novel positive feedback loop between CXCR7 and the Hippo/YAP axis, and blockade of CXCR7 could be a plausible strategy for gastric cancer.

Abstract Background Physical exercise is the first-line intervention for prediabetes, and metformin is the most widely used oral insulin-sensitizing agent. Moreover, intermuscular adipose tissue (IMAT) directly affects insulin resistance by helping maintain glucose homeostasis. Here, we evaluated the effects of moderate aerobic exercise and/or metformin on histological IMAT parameters in non-streptozotocin-induced prediabetes. Methods Male Wistar rats with prediabetes fed a high-fat diet and high-sugar drinks were randomly assigned to high-fat diet (PRE), metformin (MET), moderate aerobic exercise (EXE), combined therapy (EMC), or EMC + compound-c (EMA) groups for 4 weeks. Multimodal magnetic resonance imaging (MRI) was then performed, and tissue-specific inflammation and energy and lipid metabolism were evaluated in IMAT. Results The EXE group had lower inflammatory factor levels, lipid metabolism, and mitochondrial oxidative stress, and shorter IMAT adipocyte diameters than the MET group. The MET group exhibited lower IL-1β and Plin5 expression than the PRE group. Furthermore, the IMAT of the EMC group had lower TNF-α and phosphorylated NF-κB levels and higher GLUT1 and GLUT4 expression than the PRE group. Multimodal MRI revealed significant changes in transverse-relaxation time 2, apparent diffusion coefficient, and fractional anisotropy values in the IMAT and muscles, as well as lower IMAT% values in the EXE and EMC groups than in the MET and PRE groups. Conclusion Moderate aerobic exercise training can effectively improve IMAT function and structure via the AMP-activated protein kinase pathway in prediabetes. Combining metformin with moderate aerobic exercise might elicit modest synergy, and metformin does not counterbalance the beneficial effects of exercise.

Bi-doped Sn–Ag–Cu (SAC) microelectronic solder is gaining attention for its utility as a material for solder joints that connect substrates to printed circuit boards (PCB) in future advanced packages, as Bi-doped SAC is reported to have a lower melting temperature, higher strength, higher wettability on conducting pads, and lower intermetallic compound (IMC) formation at the solder-pad interface. As solder joints are subjected to aging during their service life, an investigation of aging-induced changes in the microstructure and mechanical properties of the solder alloy is needed before its wider acceptance in advanced packages. This study focuses on the effects of 1 to 3 wt.% Bi doping in an Sn–3.0Ag–0.5Cu (SAC305) solder alloy on aging-induced changes in hardness and creep resistance for samples prepared by high cooling rates (>5 °C/s). The specimens were aged at ambient and elevated temperatures for up to 90 days and subjected to quasistatic nanoindentation to determine hardness and nanoscale dynamic nanoindentation to determine creep behavior. The microstructural evolution was investigated with a scanning electron microscope in tandem with energy-dispersive spectroscopy to correlate with aging-induced property changes. The hardness and creep strength of the samples were found to increase as the Bi content increased. Moreover, the hardness and creep strength of the 0–1 wt.% Bi-doped SAC305 was significantly reduced with aging, while that of the 2–3 wt.% Bi-doped SAC305 increased with aging. The changes in these properties with aging were correlated to the interplay of multiple hardening and softening mechanisms. In particular, for 2–3 wt.% Bi, the enhanced performance was attributed to the potential formation of additional Ag3Sn IMCs with aging due to non-equilibrium solidification and the more uniform distribution of Bi precipitates. The observations that 2–3 wt.% Bi enhances the hardness and creep strength of the SAC305 alloy with isothermal aging to mitigate reliability risks is relevant for solder samples prepared using high cooling rates.

Sn-Ag-Cu-Bi (SAC-Bi) alloys are gaining popularity as a potential replacement for current lead-free solder alloys in microelectronic packages. In this study, the tensile and viscoplastic behaviors of eight SAC-Bi alloys with 0, 1 wt.%, 2 wt.%, and 3 wt.% Bi content were investigated. The samples of these eight alloys were cast, aged at room temperature, 75 °C and 125 °C, and tensile-tested at rates of 0.1/s, 0.01/s, and 0.001/s in ambient and elevated temperature environments to facilitate the quantification of viscoplasticity using the Anand viscoplastic model. The Anand parameters of all eight alloys in the as-cast and aged conditions were determined. Tensile strength was found to increase with the addition of Bi. Additionally, alloys containing 2 and 3 wt.% Bi showed a 5 to 10% increase in tensile strength after isothermal aging of 90 days at 125 °C. On the contrary, the tensile strength of alloys with up to 1 wt.% Bi decreased by 22 to 48% after such aging. Using a Scanning Electron Microscope (SEM) and energy dispersive spectroscopy (EDS), the microstructure of the alloys was characterized. The aging-induced property changes in the samples were correlated to strengthening by Bi solute atoms for alloys with 1 wt.% Bi and the formation of Bi precipitation for alloys with 2 wt.% and 3 wt.% Bi.

In deep carbonate reservoirs, testing and production with open-hole completion can help release the maximum production capacity. However, because the reservoir is subjected to high in situ stress, if the test pressure differential is too large, the wellbore collapse and instability will occur easily, causing downhole accidents. Therefore, it is necessary to determine the state of the borehole during the open-hole test in the carbonate reservoir and analyze the ultimate test pressure differential accordingly to ensure test safety. Considering the characteristics of open-hole completion, based on the mechanical properties of the carbonate reservoir and the stress distribution around the borehole during testing, a calculation method of the elastic zone, plastic zone, and residual failure zone around the open-hole wellbore was proposed. Regarding actual engineering data, a criterion for the overall stability of the open-hole section had been established from three aspects: the volume ratio of the plastic zone; the failure zone around the wellbore; and the failure angle on the borehole wall. According to this criterion, it is possible to determine the ultimate pressure differential during the open-hole test process and provide theoretical support for designing the open-hole completion test and production parameters for deep carbonate reservoirs.

Abstract Synovial sarcoma (SS) is a rare malignant soft tissue sarcoma that originates from primitive mesenchymal cells with epithelial differentiation potential. It is most commonly found in the limbs and trunk. In the urinary system, it is mostly found in the kidneys. However, synovial sarcomas originating from the external urethra are extremely rare. Only one case of synovial sarcoma arising from the vulvar urethral orifice has been reported previously, and we report a second case of synovial sarcoma of the urethral orifice. In addition, a total of 16 vulvar synovial sarcomas were identified and the literature are analyzed in this report reviews from 1966 to the present.

Excessive long-term manganese intake can inflict irreversible damage to the nervous system, with a predominant effect on the substantia nigra-striatum pathway. Through a mouse model simulating manganese exposure, we delved into its implications on the central nervous motor system, uncovering autophagy-lysosome dysfunction as a pivotal factor in manganese-induced neurotoxicity. Our research illuminated the molecular mechanisms behind TFEB’s role in manganese-triggered neuronal autophagy dysfunction, offering insights into the cellular and molecular mechanisms of manganese-induced abnormal protein accumulation. This study lays a significant theoretical foundation for future endeavors aimed at safeguarding against manganese neurotoxicity. Furthermore, TFEB emerges as a potential early molecular biomarker for manganese exposure, providing a solid basis for preemptive protection and clinical treatment for populations exposed to manganese.

Background/PurposeSleep quality significantly impacts subjective well-being, yet its underlying mechanisms remain largely unknown from a scholarly perspective. Existing research has inadequately addressed the relationship between sleep quality and the subjective well-being of College students. This study primarily investigates the influence of sleep quality on the subjective well-being of College students and explores the mediating role of resilience and the moderating role of belief in a just world.MethodsThe study sample comprises 3349 enrolled College students. Measures include the Pittsburgh Sleep Quality Index, the Subjective Well-being Scale, resilience scale, and belief in a just world scale. A moderated mediation model is employed to verify the mediating role of resilience and the moderating role of belief in a just world.Results(1) Sleep quality among College students is significantly positively correlated with resilience, belief in a just world, and subjective well-being. (2) Sleep quality positively predicts subjective well-being among College students. Resilience among College students serves as a mediator between sleep quality and subjective well-being, while belief in a just world moderates the influence of resilience on subjective well-being.ConclusionThe results suggest that sleep quality can directly enhance the subjective well-being of College students and can also indirectly affect it through resilience. Additionally, belief in a just world can enhance the promoting effect of resilience on the subjective well-being of College students. These findings may contribute to understanding the impact of sleep quality on the subjective well-being of College students and its pathways. These research findings can serve as a reference for improving the subjective well-being of College students.

Abstract Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide. The Hippo signaling pathway has emerged as a significant suppressive pathway for hepatocellular carcinogenesis. The core components of the Hippo pathway constitute a kinase cascade, which inhibits the functional activation of YAP/TAZ. Interestingly, the overactivation of YAP/TAZ is commonly observed in hepatocellular carcinoma, although the inhibitory kinase cascade of the Hippo pathway is still functional. Recent studies have indicated that the ubiquitin‒proteasome system also plays important roles in modulating Hippo signaling activity. Our DUB (deubiquitinase) siRNA screen showed that USP1 is a critical regulator of Hippo signaling activity. Analysis of TCGA data demonstrated that USP1 expression is elevated in HCC and associated with poor survival in HCC patients. RNA sequencing analysis revealed that USP1 depletion affects Hippo signaling activity in HCC cell lines. Mechanistic assays revealed that USP1 is required for Hippo/TAZ axis activity and HCC progression. USP1 interacted with the WW domain of TAZ, which subsequently enhanced TAZ stability by suppressing K11-linked polyubiquitination of TAZ. Our study identifies a novel mechanism linking USP1 and TAZ in regulating the Hippo pathway and one possible therapeutic target for HCC.

North China is one of the high-risk areas for destructive and strong earthquakes in mainland China and has experienced numerous strong historical earthquakes. An earthquake of magnitude MW 5.5 struck Pingyuan County, Dezhou city, in Shandong Province, China, on 6 August 2023. This earthquake was the strongest in the eastern North China Craton since the 1976 Tangshan earthquake. Since the earthquake did not produce surface ruptures, the seismogenic structure for fault responsible for the Pingyuan MW 5.5 earthquake is still unclear. To reveal the subsurface geological structure near the earthquake epicenter, this study used high-resolution two-dimensional (2D) seismic reflection profiles and constructed a three-dimensional (3D) geometric model of the Tuqiao Fault by interpreting the faults in the seismic reflection profiles. This study further combined focal mechanism solutions, aftershock clusters, and other seismological data to discuss the seismogenic fault of the Pingyuan MW 5.5 earthquake. The results show that the Tuqiao Fault is not the seismogenic fault of the MW 5.5 earthquake. The actual seismogenic structure may be related to the NE-oriented high-angle strike-slip blind fault developed in the basement. We further propose three possible fault models for the strong seismogenic structure in North China to discuss the potential seismotectonics in this region.

Human Activity Recognition (HAR) refers to a field that aims to identify human activities by adopting multiple techniques. In this field, different applications, such as smart homes and assistive robots, are introduced to support individuals in their Activities of Daily Living (ADL) by analyzing data collected from various sensors. Apart from wearable sensors, the adoption of camera frames to analyze and classify ADL has emerged as a promising trend for achieving the identification and classification of ADL. To accomplish this, the existing approaches typically rely on object classification with pose estimation using the image frames collected from cameras. Given the existence of inherent correlations between human–object interactions and ADL, further efforts are often needed to leverage these correlations for more effective and well justified decisions. To this end, this work proposes a framework where Graph Neural Networks (GNN) are adopted to explicitly analyze human–object interactions for more effectively recognizing daily activities. By automatically encoding the correlations among various interactions detected through some collected relational data, the framework infers the existence of different activities alongside their corresponding environmental objects. As a case study, we use the Toyota Smart Home dataset to evaluate the proposed framework. Compared with conventional feed-forward neural networks, the results demonstrate significantly superior performance in identifying ADL, allowing for the classification of different daily activities with an accuracy of 0.88. Furthermore, the incorporation of encoded information from relational data enhances object-inference performance compared to the GNN without joint prediction, increasing accuracy from 0.71 to 0.77.

Aerobic fitness is a critical aspect of overall health and well-being, essential for maintaining a high quality of life. Unfortunately, sedentary behavior has been on the rise among young adults, and this has had a negative impact on their aerobic fitness levels. Therefore, it is crucial to identify enjoyable physical exercise training programs that can play a pivotal role in improving aerobic fitness. The objective of this study was to systematically review the experimental studies concerning the impact of small-sided games (SSGs) training programs, implemented across various team sports, on the enhancement of aerobic fitness in a youth sedentary population. A literature search was conducted in PubMed, Scopus, and the Web of Science on August 01, 2023. Our eligibility criteria focused on studies involving sedentary youth populations (aged

IntroductionAcademic misconduct among graduate students poses a significant challenge in graduate education. This study aims to explore the impact of innovative behavior on graduate student academic misconduct and its underlying mechanisms.MethodsA survey was conducted on 677 graduate students currently enrolled in Beijing universities to assess their innovative behavior, academic misconduct, academic anxiety, employment confidence, educational levels, among other factors. The study analyzed the mediating roles of academic anxiety, employment confidence, and educational levels in the relationship between innovative behavior and graduate student academic misconduct.ResultsGraduate student innovative behavior exerts a negative predictive effect on academic misconduct, with a stronger emphasis on innovative behavior associated with a reduced likelihood of academic misconduct. Academic anxiety plays a mediating role in the relationship between graduate student innovative behavior and academic misconduct. Educational levels and employment confidence each play moderating roles in the latter stages of the mediation effects concerning graduate student innovative behavior, academic anxiety, and academic misconduct.ConclusionThis study reveals the mediating role of academic anxiety in the relationship between innovative behavior and graduate student academic misconduct. It also identifies the moderating roles of employment confidence and educational levels. These findings deepen our understanding of the relationship between innovative behavior and graduate student academic misconduct and are conducive to preventing such misconduct among graduate students.

Highlights 1. RNF31 restrains cancer cell progression in TNBC. 2. RNF31 regulates YAP protein stability via promoting YAP K48-linked poly-ubiquitination. 3. RNF31 represses immune evasion via suppressing YAP/PD-L1 axis in TNBC.

Abstract Background Triple negative breast cancer (TNBC) is one of the most lethal breast cancer subtypes. Due to a lack of effective therapeutic targets, chemotherapy is still the main medical treatment for TNBC patients. Thus, it is important and necessary to find new therapeutic targets for TNBC. Recent genomic studies implicated the Hippo / Yap signal is over activated in TNBC, manifesting it plays a key role in TNBC carcinogenesis and cancer progression. RBCK1 was firstly identified as an important component for linear ubiquitin assembly complex (LUBAC) and facilitates NFKB signaling in immune response. Further studies showed RBCK1 also facilitated luminal type breast cancer growth and endocrine resistance via trans-activation estrogen receptor alpha. Methods RBCK1 and YAP protein expression levels were measured by western blotting, while the mRNA levels of YAP target genes were measured by RT–PCR. RNA sequencing data were analyzed by Ingenuity Pathway Analysis. Identification of Hippo signaling activity was accomplished with luciferase assays, RT–PCR and western blotting. Protein stability assays and ubiquitin assays were used to detect YAP protein degradation. Ubiquitin-based immunoprecipitation assays were used to detect the specific ubiquitination modification on the YAP protein. Results In our current study, our data revealed an opposite function for RBCK1 in TNBC progression. RBCK1 over-expression inhibited TNBC cell progression in vitro and in vivo, while RBCK1 depletion promoted TNBC cell invasion. The whole genomic expression profiling showed that RBCK1 depletion activated Hippo/YAP axis. RBCK1 depletion increased YAP protein level and Hippo target gene expression in TNBC. The molecular biology studies confirmed that RBCK1 could bind to YAP protein and enhance the stability of YAP protein by promoting YAP K48-linked poly-ubiquitination at several YAP lysine sites (K76, K204 and K321). Conclusion Our study revealed the multi-faced RBCK1 function in different subtypes of breast cancer patients and a promising therapeutic target for TNBC treatment. Video abstract

Lamprey underwent biliary atresia (BA) at its metamorphosis stage. In contrast to patients with BA who develop progressive disease, lamprey can grow and develop normally, suggesting that lamprey has several adaptations for BA. Here we show that adaptive changes in bile acid and cholesterol metabolism are produced after lamprey BA. Among 1102 differentially expressed genes (DGEs) after BA in lamprey, many are enriched in gene ontology (GO) terms and pathways related to steroid metabolism. We find that among the DGEs related to bile acids and cholesterol metabolism, the expression of cytochrome P450 family 7 subfamily A member 1 (CYP7A1), sodium-dependent taurine cotransport polypeptide (NTCP) are significantly downregulated, whereas nuclear receptor farnesoid X receptor (FXR), multidrug resistance-associated protein 3 (MRP3), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), sterol O-acyltransferase 1 (SOAT1), and ATP binding cassette subfamily A member 1 (ABCA1) are remarkably upregulated. The changes in expression level are also validated by RT-qPCR. Furthermore, the level of high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C) in juvenile serum is higher compared to larvae. Taken together, the findings collectively indicate that after BA, lamprey may maintain bile acids and cholesterol homeostasis in liver tissue by inhibiting bile acids synthesis and uptake, promoting its efflux back to circulation, and enhancing cholesterol esterification for storage as lipid droplets and its egress to form nascent HDL (nHDL). Understanding the possible molecular mechanisms of lamprey metabolic adaptation sheds new light on the understanding of the development and treatment of diseases caused by abnormal bile acid and cholesterol metabolism in humans.

Abstract The 2019 novel coronavirus disease (COVID‐19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is ongoing, and has necessitated scientific efforts in disease diagnosis, treatment, and prevention. Interestingly, extracellular vesicles (EVs) have been crucial in these developments. EVs are a collection of various nanovesicles which are delimited by a lipid bilayer. They are enriched in proteins, nucleic acids, lipids, and metabolites, and naturally released from different cells. Their natural material transport properties, inherent long‐term recycling ability, excellent biocompatibility, editable targeting, and inheritance of parental cell properties make EVs one of the most promising next‐generation drug delivery nanocarriers and active biologics. During the COVID‐19 pandemic, many efforts have been made to exploit the payload of natural EVs for the treatment of COVID‐19. Furthermore, strategies that use engineered EVs to manufacture vaccines and neutralization traps have produced excellent efficacy in animal experiments and clinical trials. Here, the recent literature on the application of EVs in COVID‐19 diagnosis, treatment, damage repair, and prevention is reviewed. And the therapeutic value, application strategies, safety, and biotoxicity in the production and clinical applications of EV agents for COVID‐19 treatment, as well as inspiration for using EVs to block and eliminate novel viruses are discussed.

Neurotoxicity caused by environmental lead (Pb) pollution is a worldwide public health concern, and developing a therapeutic strategy against Pb-induced neurotoxicity is an important area in the current research. Our prior research has demonstrated the significant involvement of microglia-mediated inflammatory responses in the manifestation of Pb-induced neurotoxicity. Additionally, the suppression of proinflammatory mediator activity significantly mitigated the toxic effects associated with Pb exposure. Recent studies have highlighted the critical role of the triggering receptor expressed on myeloid cells 2 (TREM2) in the pathogenesis of neurodegenerative disorders. TREM2 exerted protective effects on inflammation, but whether TREM2 is involved in Pb-induced neuroinflammation is poorly understood. In the present study, cell culture experiments and animal models were designed to investigate the role of TREM2 in Pb’s neuroinflammation. We examined the impact of pro- and anti-inflammatory cytokines involved in Pb-induced neuroinflammation. Flow cytometry and microscopy techniques were applied to detect microglia phagocytosis and migration ability. Our results showed that Pb treatment significantly downregulated TREM2 expression and altered the localization of TREM2 expression in microglia. The protein expression of TREM2 was restored, and the inflammatory responses provoked by Pb exposure were ameliorated upon the overexpression of TREM2. Furthermore, the phagocytosis and migratory capabilities of microglia, which were impaired due to Pb exposure, were alleviated by TREM2 overexpression. Our in vitro findings were corroborated in vivo, demonstrating that TREM2 regulates the anti-inflammatory functions of microglia, thereby mitigating Pb-induced neuroinflammation. Our results provide insights into the detailed mechanism by which TREM2 alleviates Pb-induced neuroinflammation and suggest that activating the anti-inflammatory functions of TREM2 may represent a potential therapeutic strategy against environmental Pb-induced neurotoxicity.

Para-testicular rhabdomyosarcoma (PTRMS) is a rare tumor, and it accounts for 7% of all rhabdomyosarcoma tumors. Among all the rhabdomyosarcoma (RMS) types, the spindle cell RMS is extremely rare. The present study describes a case of a para-testicular spindle cell RMS that was treated with a radical inguinal orchiectomy (RIO) and right scrotal resection. A 17-year-old male patient presented with a half-year history of a rapidly growing, painless, right scrotal mass. His CT of the pelvic cavity showed a mixed-density mass in the right scrotum, and the maximum cross-sectional area was approximately 76.5 mm × 64.5 mm. An X-ray of the chest demonstrated no evidence of metastasis, and a local surgical excision was performed subsequently. The histopathological and immunohistochemical examination confirmed the final diagnosis of spindle cell RMS. As a newly diagnosed case, strict and regular follow-up is needed. This article focuses on the importance of prompt recognition, diagnosis, pathological features, and appropriate management of para-testicular spindle cell RMS.

The economic efficiency of sheep breeding can be improved by enhancing sheep productivity. A recent genome-wide association study (GWAS) unveiled the potential impact of the MAST4 gene on prolificacy traits in Australian White sheep (AUW)). Herein, whole-genome sequencing (WGS) data from 26 different sheep breeds worldwide (n = 1507), including diverse meat, wool, milk, or dual-purpose sheep breed types from China, Europe, and Africa, were used. Moreover, polymerase chain reaction (PCR) genotyping of the MAST4 gene polymorphisms in (n = 566) Australian white sheep (AUW) was performed. The 3 identified polymorphisms were not homogeneously distributed across the 26 examined sheep breeds. Findings revealed prevalent polymorphisms (P3-ins-29 bp and P6-del-21 bp) with varying frequencies (0.02 to 0.97) across 26 breeds, while P5-del-24 bp was presented in 24 out of 26 breeds. Interestingly, the frequency of the P3-ins-29 bp variant was markedly higher in Chinese meat or dual-purpose sheep breeds, while the other two variants also showed moderate frequencies in meat breeds. Notably, association analysis indicated that all InDels were associated with AUW sheep litter size (p < 0.05). These results suggest that these InDels within the MAST4 gene could be useful in marker-assisted selection in sheep breeding.

Understanding the factors that hamper immune therapy in breast cancer may increase the range of patients who benefit. Here authors show that breast cancer cells produce and subsequently transfer active TGF-β type II receptors to CD8 + T cells to render them exhausted, thus paralyzing the anti-tumor immune response.

Abstract To ensure the power quality of a ship power system under disturbances due to changing sea states, an adaptive bus‐voltage controller with online load power fluctuation prediction is proposed to stabilize the ship bus voltage. The controller uses an online sequence extreme learning machine to update the output weight matrix and achieve an accurate online prediction of the ship load power fluctuations under the disturbance of random uncertainties. A stable additional control signal is provided to the bus‐voltage controller for adaptive operation. The prediction results are used to optimize the coordinated control of multiple generation systems and improve the bus‐voltage control performance by updating the droop control coefficients online. The adaptability provided by the online prediction algorithm and the performance of the bus‐voltage control are verified using recorded voyage data of an offshore marine engineering transport vessel.

The Albertine Basin is an important rift basin in the East African Rift System, enriched in oil and gas resources. The upper Miocene to lower Pliocene hydrocarbon source rocks are important source rocks in the basin, but the research is relatively limited. In this work, we evaluate the source rocks of the upper Miocene and lower Pliocene in the Albertine Basin by integrations of geological, rock pyrolysis and elemental geochemistry data and analyses the paleoenvironmental evolutions of the late Miocene to early Pliocene. These results show that the two sets of source rocks are under the mature stage, but the abundance and type of organic matter are different. The lower Pliocene source rocks have higher organic matter abundance and belong to middle-good source rocks, yielding type Ⅱ1 -Ⅱ2 kerogen. The upper Miocene source rocks have lower organic matter abundance and belong to poor source rocks, yielding type Ⅱ2-Ⅲ kerogen. The sedimentary environment is an important controlling factor for the difference in source rocks. During the late Miocene to early Pliocene, the study area was a freshwater lake with strong reducibility, gradually increasing water depth, a warmer climate, flourishing bacteria and microorganisms, and better organic matter types. At the same time, lake productivity is elevated, the sedimentation rate is accelerated, and organic matter can be preserved more efficiently, so the abundance of organic matter in source rocks is higher.

Abstract Progranulin (PGRN) is an autocrine growth factor that regulates cell proliferation, migration, wound healing, and tissue repair in mammals. Lamprey is the most primitive of the extant vertebrates and is regarded as the survivor of a once flourishing group of paleozoic vertebrates, with a history of more than 500 million years. To date, the evolutionary dynamics and the underlying function of the PGRNs remain largely unclear in lamprey. Here, we screened four genes encoding PGRNs from the genomes of Lethenteron reissneri and Petromyzon marinus, including one long form (named Lr-PGRN-L) and three short forms (named Lr-PGRN-S1, Lr-PGRN-S2, and Lr-PGRN-S3), and performed phylogenetic tree, functional domain, and synteny analyses to identify the evolutionary history of the four Lr-PGRNs. In addition, the expressions of the four Lr-pgrn family genes and the immune response against various pathogenic challenges were also investigated. We found that these genes were widely distributed in various tissues of lamprey and performed a variety of functions. Moreover, our results suggest that Lr-PGRN-S1 induces cell migration and proliferation, and is involved in repair after skin and spinal cord injury under appropriate conditions. Our findings are valuable because they improve the understanding of the evolutionary relationship of vertebrate pgrn genes, as well as providing new insights into the diverse and important roles of Lr-PGRNs.

Highlights 1. DUB1 is an important modulator of Hippo signaling in gastric cancer. 2. DUB1 expression is elevated in human gastric cancer samples and correlates with poor survival in gastric cancer. 3. DUB1 facilitates gastric cancer progression via the Hippo/TAZ axis. 4. DUB1 associates with TAZ and directly inhibits YAP polyubiquitination and degradation.

Recent studies have reported that oncoprotein YAP can function as tumour suppressor in certain contexts. Here the authors show that inhibition of Hippo signalling or YAP activation blocks ERα transcriptional program and ER + breast cancer growth and mechanistically this is through YAP interfering with TEAD-ERα signalling axis.

Abstract Long noncoding RNAs (lncRNAs) play important regulatory roles in a variety of pathological processes involving cancer. However, the exact molecular mechanisms of lncRNA regulation in endometrial carcinoma (EC) remain poorly defined. The aim of this study was to illustrate the mechanism of LINC00958 in regulating the function of IGF2BP3, an RNA binding protein involved in mRNA stability, and their clinical implications in EC. First, we investigated the clinical role of IGF2BP3 in EC and demonstrated its prognostic value. Loss-of-function and gain-of-function studies showed that IGF2BP3 promoted EC cell proliferation, migration and invasion. Then, we carried out RNA immunoprecipitation sequencing (RIP-seq) analysis, RNA pulldown and immunofluorescence-RNA fluorescence in situ hybridization to identify LINC00958 that interacted with IGF2BP3 in the cytoplasm of EC cells. Rescue experiments indicated that knockdown of LINC00958 partially offset the EC cell progression mediated by IGF2BP3. After that, RNA sequencing was used to screen out the downstream genes of IGF2BP3 and LINC00958. The results revealed that IGF2BP3 upregulated E2F3 expression by interacting with LINC00958. Furthermore, RNA stability assays demonstrated that silencing LINC00958 partially rescued the IGF2BP3-mediated promoting effect on the mRNA stability of E2F3. Collectively, this study suggests that LINC00958, as an oncogene, assists IGF2BP3 in stabilizing E2F3 mRNA and ultimately promotes EC progression, providing a promising therapeutic target for patients with EC.