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Abstract Palbociclib is a CDK4/6 inhibitor approved for the treatment of breast cancer by suppressing cell proliferation. However, monotherapy with palbociclib was discouraging in prostate cancer, calling for a mechanism-based effective therapy. In this study, we reported in prostate cancer that palbociclib is a potent sensitizer of ferroptosis, which is worked out by downregulating the expression of TRIB3, a gene highly expressed in prostate cancer. Specifically, TRIB3 knockdown augmented the response of prostate cancer cells to ferroptosis inducers, whereas, TRIB3 overexpression rescued prostate cancer cells from palbociclib-induced ferroptosis. Mechanistically, TRIB3 inhibition by palbociclib resulted in downregulation of SOX2, which subsequently led to compromised expression of SLC7A11, a cystine/glutamate antiporter that counteracts ferroptosis. Functionally, a combined treatment of palbociclib with ferroptosis inducer significantly suppressed prostate cancer growth in a xenograft tumor model. Together, these results uncover an essential role of TRIB3/SOX2/SLC7A11 axis in palbociclib-induced ferroptosis, suggesting palbociclib a promising targeted therapy in combine with ferroptosis induction for the treatment of prostate cancer.

Bariatric surgery is an effective treatment for type 2 Diabetes Mellitus (T2DM), yet the precise mechanisms underlying its effectiveness remain incompletely understood. While previous research has emphasized the role of rearrangement of the gastrointestinal anatomy, gaps persist regarding the specific impact on the gut microbiota and barriers within the biliopancreatic, alimentary, and common limbs. This study aimed to investigate the effects of duodenal-jejunal bypass (DJB) surgery on obese T2DM mice. We performed DJB and SHAM surgery in obese T2DM mice to investigate changes in the gut microbiota and barrier across different intestinal limbs. The effects on serum metabolism and potential associations with T2DM improvement were also investigated. Following DJB surgery, there was an increased abundance of commensals across various limbs. Additionally, the surgery improved intestinal permeability and inflammation in the alimentary and common limbs, while reducing inflammation in the biliopancreatic limbs. Furthermore, DJB surgery also improved T2DM by increasing L-glutamine, short-chain fatty acids, and bile acids and decreasing branched-chain amino acids. This study underscores the role of intestinal rearrangement in reshaping gut microbiota composition and enhancing gut barrier function, thereby contributing to the amelioration of T2DM following bariatric surgery, and providing new insights for further research on bariatric surgery.

Breast phyllodes tumor (PT) is a rare fibroepithelial neoplasm with potential malignant behavior. Long non-coding RNAs (lncRNAs) play multifaceted roles in various cancers, but their involvement in breast PT remains largely unexplored. In this study, microarray was leveraged for the first time to investigate the role of lncRNA in PT. We identified lncRNA ZFPM2-AS1 was significantly upregulated in malignant PT, and its overexpression endowed PT with high tumor grade and adverse prognosis. Furthermore, we elucidated that ZFPM2-AS1 promotes the proliferation, migration, and invasion of malignant PT in vitro. Targeting ZFPM2-AS1 through nanomaterial-mediated siRNA delivery in patient-derived xenograft (PDX) model could effectively inhibit tumor progression in vivo. Mechanistically, our findings showed that ZFPM2-AS1 is competitively bound to CDC42, inhibiting ACK1 and STAT1 activation, thereby launching the transcription of TNFRSF19. In conclusion, our study provides evidence that ZFPM2-AS1 plays a pivotal role in the pathogenesis of breast PT, and suggests that ZFPM2-AS1 could serve as a prognostic indicator for patients with PT as well as a promising novel therapeutic target.

Abstract Despite limited research on refractory and/or endocrine therapy failure in elderly metastatic breast cancer (MBC) patients, a prior study showed that low-dose oral cyclophosphamide (CY) can improve the overall survival rate of MBC patients, possibly through the immunoregulation of regulatory T cells (Tregs). We preliminarily investigated the combination of endocrine therapy (ET) with oral low-dose CY as salvage therapy in elderly patients via peripheral blood regulatory T-cell analyses. In addition, we evaluated the associations of tumor tertiary lymphoid structures (TLSs) with therapeutic outcomes. HR+/HER2− advanced breast cancer patients who received low-dose CY combined with ET or ET only from April 2015 to August 2021 were enrolled in this retrospective study. The primary outcome was the clinical control rate (CCR), and the secondary outcome was progression-free survival (PFS). Circulating T lymphocyte subpopulations represented by Tregs were monitored during treatment by flow cytometry methods. TLSs wereconfirmed by hematoxylin–eosin staining of pretreatment specimens, and CD3, CD4, and Foxp3 were detected using Opal multicolor immunofluorescence. A total of 85 patients who received CY + ET and 50 patients who received ET only were enrolled, the percentage of patients who received CCR was 73% (62/85) vs. 70% (45/50), and the objective response rate (ORR) was 28% (24/85) vs. 24% (12/50). No deaths occurred during the study period. The mean PFS time was 13 vs. 11 months (P = 0.03). In the CY + ET group, decreases in CD4+/CD25+/Foxp3+ T cells (P

This paper details and develops novel wing shape hydrocarbon fuel cooling channel for enhancing the heat transfer capability of hypersonic vehicle electricity supply blades under rotating conditions. The effect of parameters such as wing base position and height on the thermal performance in the rotating situation is studied. The calculation results show that the wing base height H = 0.6D-0.8D wing shape channels have generally higher thermal performance and generally lower friction coefficient. Thermal performance of the channel with wing base parameters L = 10 D, H = 0.6 D is maximally increased by 350.2 % and friction coefficient is maximally reduced by 98.5 % compared with the straight channel at inlet temperature of 590 K and rotational speed of 35,000 rpm. As the wing base position L increases, both the thermal performance and the friction coefficient increase and then decrease under the influence of the pressure difference. Under the condition of high rotational speed, the wing base height H = 0.8 D and H = 0.6 D wing shape channels will obtain the maximum value of thermal performance in the range of L = 2 D-4 D and L = 6 D-10 D of the wing base position, respectively.

This paper examines the impact of a polyvinylidene fluoride (PVDF) and carbon nanotube (CNT) hybrid coating on the heat transfer and hydraulic performance of serpentine microchannel heat sinks. In an aluminum serpentine microchannel heat sink using deionized water as the working fluid, the heat transfer performance and flow resistance were analyzed for different mass fluxes (G) in both PVDF-CNT coated (PSMC) and uncoated (TSMC) heat sinks under different heat flow densities. The results demonstrate that the PVDF-CNT coating enhances the heat transfer and hydraulic performance of the serpentine flow channel. Compared to the TSMC, the convective heat transfer coefficient of the PSMC increased by up to 61.9%, while the flow resistance coefficient decreased by up to 33.8%. The PVDF-CNT coating offers a superior balance of heat transfer performance and pressure drop compared to the addition of fins. A critical interval for the inlet mass flux G was identified, beyond which the heat transfer efficiency improvement of PSMC over TSMC was more pronounced.

Abstract Background The presence of mesenchymal stem cells has been confirmed in some solid tumors where they serve as important components of the tumor microenvironment; however, their role in cancer has not been fully elucidated. The aim of this study was to investigate the functions of mesenchymal stem cells isolated from tumor tissues of patients with non-small cell lung cancer. Results Human lung cancer-derived mesenchymal stem cells displayed the typical morphology and immunophenotype of mesenchymal stem cells; they were nontumorigenic and capable of undergoing multipotent differentiation. These isolated cells remarkably enhanced tumor growth when incorporated into systems alongside tumor cells in vivo. Importantly, in the presence of mesenchymal stem cells, the ability of peripheral blood mononuclear cell-derived natural killer and activated T cells to mediate tumor cell destruction was significantly compromised. Conclusion Collectively, these data support the notion that human lung cancer-derived mesenchymal stem cells protect tumor cells from immune-mediated destruction by inhibiting the antitumor activities of natural killer and T cells.

The aim of the present study was to explore the functional mechanism of NF-Kappa B-interacting Long non-protein coding RNA (NKILA) in breast malignant phyllodes tumors (BMPTs). The expression and functional role of NKILA were investigated by performing qRT‒PCR, Transwell assays, and CCK‒8 assays in primary BMPT cells. A Kaplan‒Meier curve was used to assess overall survival (OS) and local recurrence-free survival (LRFS). The location and expression levels of NKILA and P65 were determined by fluorescence in situ hybridization (FISH) and immunofluorescence (IF), respectively. NKILA was downregulated in patients with BMPT, especially in patients with local recurrence. NKILA had an antitumor effect and promoted the chemosensitivity of cells to cisplatin by blocking P65 phosphorylation and nuclear translocation. In conclusion, NKILA may be a potential therapeutic target for BMPT, especially for BMPT patients with local recurrence.

Abstract Background As a rapid‐progressing tumor, breast malignant phyllodes tumors (PTs) are challenged by the lack of effective therapeutic strategies and suitable prognostic markers. This study aimed to clarify the role and mechanism of CD146 on promoting PTs malignant progression, and to identify a novel prognosis marker and treatment target of breast malignant PTs. Methods The expression and prognostic significance of CD146 in PTs was detected through single‐cell RNA‐sequencing (scRNA‐seq), immunostaining, real‐time PCR and other methodologies. Functional experiments including proliferation assay, colony formation assay, transwell assay, and collagen contraction assay were conducted to validate the role of CD146 in malignant progression of PTs. The efficacy of anti‐CD146 monoclonal antibody AA98 against malignant PTs was corroborated by a malignant PT organoid model and a PT patient‐derived xenograft (PDX) model. Transcriptome sequencing, proteomic analysis, co‐immunoprecipitation, and pull‐down assay was employed to identify the modulating pathway and additional molecular mechanism. Results In this study, the scRNA‐seq analysis of PTs disclosed a CD146‐positive characteristic in the α‐SMA+ fibroblast subset. Furthermore, a progressive elevation in the level of CD146 was observed with the malignant progression of PTs. More importantly, CD146 was found to serve as an independent predictor for recurrence in PT patients. Furthermore, CD146 was found to augment the viability and invasion of PTs. Mechanistically, CD146 acted as a protective “shield” to prevent the degradation of Discoidin, CUB, and LCCL domain‐containing protein 2 (DCBLD2), thereby activating the phosphoinositide 3‐kinase (PI3K)/protein kinase B (AKT) signaling pathway and enhancing malignant behaviors of PT cells. In the malignant PT organoid and PDX model, a significant suppression of malignant PT growth was observed after the application of AA98. Conclusions These findings suggested that CD146 served as an efficacious marker for predicting PT malignant progression and showed promise as a prognosis marker and treatment target of breast malignant PTs. The study further unveiled the essential role of the CD146‐DCBLD2/PI3K/AKT axis in the malignant progression of PTs.

Abstract Background To develop and validate radiomics models for prediction of tumor response to neoadjuvant therapy (NAT) in patients with locally advanced rectal cancer (LARC) using both pre-NAT and post-NAT multiparameter magnetic resonance imaging (mpMRI). Methods In this multicenter study, a total of 563 patients were included from two independent centers. 453 patients from center 1 were split into training and testing cohorts, the remaining 110 from center 2 served as an external validation cohort. Pre-NAT and post-NAT mpMRI was collected for feature extraction. The radiomics models were constructed using machine learning from a training cohort. The accuracy of the models was verified in a testing cohort and an independent external validation cohort. Model performance was evaluated using area under the curve (AUC), sensitivity, specificity, positive predictive value, and negative predictive value. Results The model constructed with pre-NAT mpMRI had favorable accuracy for prediction of non-response to NAT in the training cohort (AUC = 0.84), testing cohort (AUC = 0.81), and external validation cohort (AUC = 0.79). The model constructed with both pre-NAT and post-NAT mpMRI had powerful diagnostic value for pathologic complete response in the training cohort (AUC = 0.86), testing cohort (AUC = 0.87), and external validation cohort (AUC = 0.87). Conclusions Models constructed with multiphase and multiparameter MRI were able to predict tumor response to NAT with high accuracy and robustness, which may assist in individualized management of LARC.

Abstract This study aimed to investigate the relationship between venous blood parameters and respiratory functions in patients with amyotrophic lateral sclerosis (ALS) and develop a model to predict respiratory impairment for individual patients with ALS. A total of 416 ALS patients were included in the study, and various hematologic and biochemical laboratory parameters as well as demographic and clinical factors were collected and compared. A multivariable logistic regression model was constructed to assess the association between FVC and venous blood biomarkers and clinical factors. The results showed that along with onset age, bulbar-onset, disease duration, BMI, eosinophil count (EO#), basophil count (BASO#), creatinine (CREA), uric acid (URCI) and low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL/HDL) ratio were associated with reduced FVC. The area under the ROC curve is 0.735 for the test set and 0.721 for the validation set. The study also developed a relatively acceptable model for predicting respiratory impairment in ALS patients. These findings suggest that EO#, BASO#, CREA, URIC and LDL/HDL ratio can be useful in assessing FVC in ALS and can be easily accessible, accurate, and low-cost parameters.

Abstract Background The association between gastrointestinal cancer and types of meat consumption, including red meat, processed meat, or a combination of both, remains disputable. Therefore, we performed a systematic review and meta-analysis of prospective cohort studies to estimate the association between meat consumption and gastrointestinal cancer risk. Methods PubMed, EmBase, and the Cochrane library databases were searched systematically for eligible studies that investigated the relation between meat consumption and the risk of developing gastrointestinal cancers, including esophageal cancer (EC), gastric cancer (GC), colorectal cancer (CRC), colon cancer (CC), rectal cancer (RC), pancreatic cancer (PC), and hepatocellular carcinoma (HCC) throughout February, 2023. The pooled relative risk (RR) with 95% confidence interval (CI) was assigned as an effect estimate and calculated using a random-effects model with inverse variance weighting. Results Forty cohorts comprising 3,780,590 individuals were selected for the final quantitative analysis. The summary results indicated that a higher red meat consumption was associated with an increased risk of CRC (RR: 1.09; 95% CI: 1.02–1.16; P = 0.007) and CC (RR: 1.13; 95% CI: 1.03–1.25; P = 0.011). Moreover, a higher processed meat consumption was associated with an increased risk of CRC (RR: 1.19; 95% CI: 1.13–1.26; P

Junctional adhesion molecule-A (JAM-A), also known as F11 receptor (F11R), is a transmembrane glycoprotein that is involved in various biological processes, including cancer initiation and progression. However, the functional characteristics and significance of JAM-A in pan-cancer remain unexplored. In this study, we used multiple databases to gain a comprehensive understanding of JAM-A in human cancers. JAM-A was widely expressed in various tissues, mainly located on the microtubules and cell junctions. Aberrant expression of JAM-A was detected in multiple cancers at both mRNA and protein levels, which can be correlated with poorer prognosis and may be attributed to genetic alterations and down-regulated DNA methylation. JAM-A expression was also associated with immune infiltration and may affect immunotherapy responses in several cancers. Functional enrichment analysis indicated that JAM-A participated in tight junction and cancer-related pathways. In vitro experiments verified that JAM-A knockdown suppressed the proliferation and migration abilities of breast cancer cells and liver cancer cells. Overall, our study suggests that JAM-A is a pan-cancer regulator and a potential biomarker for predicting prognosis and immune-therapeutic responses for different tumors.

Background. In the context of hepatocellular carcinoma (HCC), tumor-associated macrophages (TAMs) are pivotal for the immunosuppressive nature of the tumor microenvironment (TME). This investigation delves into the functional transformations of TAMs within the TME by leveraging single-cell transcriptomics to pinpoint critical genes influencing TAM subset polarization. Methods. We procured single-cell and bulk transcriptomic data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA), implementing quality assurance, dimensional reduction, clustering, and annotation on the single-cell sequencing data. To examine cellular interactions, CellChat was utilized, while single-cell regulatory network inference and clustering (SCENIC) was applied to deduce transcription factors (TFs) and their associated targets. Through gene enrichment, survival, and immune infiltration correlation analyses, we sought to pinpoint and validate influential genes. A TAM model under HCC conditions was then established to confirm the expression levels of these key genes. Results. Our analysis encompassed 74,742 cells and 23,110 genes. Through postdimensional reduction and clustering, we identified seven distinct cell types and nine TAM subtypes. Analysis via CellChat highlighted a predominance of M2-phenotype-inclined TAM subsets within the tumor’s core. SCENIC pinpointed the transcription factor PRDM1 and its target genes as pivotal in this region. Further analysis indicated these genes’ involvement in macrophage polarization. Employing trajectory analysis, survival analysis, and immune infiltration correlation, we scrutinized and validated genes likely directing M2 polarization. Experimental validation confirmed PRDM1’s heightened expression in TAMs conditioned by HCC. Conclusions. Our findings suggest the PRDM1 gene is a key regulator of M2 macrophage polarization, contributing to the immunosuppressive TME in HCC.

BackgroundWhile dietary factors have shown an association with Parkinson’s disease (PD), the available data remains a subject of ongoing debate and controversy.AimWe sought to evaluate potential relationships between dietary consumption of nutrients and micronutrients and risk of PD in a large sample.MethodsCross-sectional data were retrospectively analyzed for 10,651 adults aged 40–80 years that had been collected in the US between 2007 and 2016 as a component of the nationwide National Health and Nutrition Examination Survey. Aspects of dietary intake were compared between those who reported having specific PD medication regimens or not when they completed the survey, and potential associations between diet and risk of PD were explored using binomial logistic regression. We employed Propensity Score Matching (PSM) to minimize the impact of potential confounding factors, thus enhancing the reliability of the results. Additionally, subgroup analysis based on gender and age was conducted to investigate these relationships.ResultsHigher dietary intake of iron was linked to greater PD risk [odds ratio (OR) 1.065, 95% confidence interval (CI) 1.019–1.114, p = 0.006], whereas risk decreased with higher intake of vitamin K (OR 0.999, 95% CI 0.998–1.000, p = 0.024) or vitamin C (OR 0.998, 95% CI 0.996–0.999, p = 0.039). Even after applying PSM, the connection between dietary iron intake and dietary vitamin C intake with PD risk remained substantial. Subgroup analysis results revealed a significant positive association between dietary intake of iron from food and the PD risk, which was evident among individuals under 60 years of age and among males.ConclusionThe intake of micronutrients can influence risk of PD, which should be verified and explored further in prospective samples with other dietary habits and ethnic backgrounds.

Breast phyllodes tumors (PTs) are biphasic, with epithelial and stromal components. Although the PT incidence is low (approximately 1% of all breast tumors), its clinical outcomes are unpredictable, and malignant PTs often progress rapidly. No effective treatment is currently available, thus resulting a high mortality rate from malignant PTs. PT cell lines must be established to facilitate the study of PTs. Herein, we established six PT cell lines through continuous passage or cell immortalization. We characterized these PT cell lines through in vitro functional assays, malignant PT marker detection and short tandem repeat identification. Benign PT cell lines (SYSH-BPT-01 and SYSH-BPT-02) were transfected with human papillomavirus 16 E6/E7, and two malignant PT cell lines (SYSH-MPT-01 and SYSH-MPT-02) were transfected with Simian virus 40 large T antigen. Two malignant PT cell lines (SYSH-MPT-03 and SYSH-MPT-04) were established through continuous passage. All malignant PT cell lines showed greater proliferation, colony formation, migration, invasion and collagen contraction ability than the benign PT cell lines. Moreover, the expression levels of malignant PT markers (α-smooth muscle actin and fibroblast activation protein) and short tandem repeat identification indicated that each PT cell line was identical to the parental primary cells. We successfully established PT cell lines that preserved the features of primary cells. These cell lines may serve as ideal experimental models for studying the function of breast PTs, thus opening new possibilities for PT drug screening and therapeutic target validation.

Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.

ObjectiveFreezing of gait (FOG) is common in neurodegenerative forms of atypical parkinsonism, but few studies have examined FOG in multiple system atrophy (MSA). In this study, we examined the prevalence of freezing of gait and its relationship to clinical features in a large cohort of Chinese MSA patients.MethodsThis exploratory study included 202 Chinese patients with probable MSA. FOG was defined as a score ≥ 1 on item 14 of the Unified Parkinson’s Disease Rating Scale. Patients with or without FOG were compared in terms of the Unified MSA Rating Scale (UMSARS) as well as cognitive and neuropsychiatric assessments.ResultsThe frequency of FOG was 48.0, 52.1, and 38.7% in MSA, MSA with predominant parkinsonism (MSA-P), and MSA with predominant cerebellar ataxia (MSA-C), respectively. FOG was associated with worse subscores on parts I, II and IV of the UMSARS as well as worse total UMSARS score; greater likelihood of speech difficulties, falls, gait impairment and balance disorder; more severe symptoms of anxiety and depression; and lower activities of daily living. The binary logistic regression model indicated that higher total UMSARS scores were associated with FOG in MSA, MSA-P, and MSA-C patients.ConclusionFreezing of gait may be common among Chinese MSA patients, FOG may correlate with severe motor symptoms, anxiety, depression and activities of daily living. Total UMSARS score may be an independent risk factor for FOG.

ObjectiveThis study aimed to investigate the prevalence and clinical characteristics of subjective constipation in Chinese patients with multiple system atrophy (MSA), as well as the timing of constipation onset relative to the occurrence of motor symptoms.MethodsA total of 200 patients who were consecutively admitted to two large Chinese hospitals from February 2016 to June 2021 and subsequently diagnosed with probable MSA were enrolled in this cross-sectional study. Demographic and constipation-related clinical data were collected, and motor and non-motor symptoms were assessed using various scales and questionnaires. Subjective constipation was defined using ROME III criteria.ResultsThe frequency of constipation was 53.5, 59.7, and 39.3% in MSA, MSA with predominately parkinsonism (MSA-P), and MSA with predominately cerebellar ataxia (MSA-C), respectively. MSA-P subtype and high total UMSARS scores were associated with constipation in MSA. Similarly, the high total UMSARS scores were associated with constipation in MSA-P and MSA-C patients. Among the 107 patients with constipation, 59.8% began experiencing it before the onset of motor symptoms, and the interval between constipation and occurrence of motor symptoms was significantly longer in these patients than in those who experienced constipation after onset of motor symptoms.ConclusionConstipation is a highly prevalent non-motor symptom in MSA and more often occurs before the onset of motor symptoms. The results of this study may help guide future research into MSA pathogenesis in its earliest stages.

Abstract Penetration of immune cells into tumor cells was believed to be immune-suppressive via cell-in-cell (CIC) mediated death of the internalized immune cells. We unexpectedly found that CIC formation largely led to the death of the host tumor cells, but not the internalized immune cells, manifesting typical features of death executed by NK cells; we named this “in-cell killing” which displays the efficacy superior to the canonical way of “kiss-killing” from outside. By profiling isogenic cells, CD44 on tumor cells was identified as a negative regulator of “in-cell killing” via inhibiting CIC formation. CD44 functions to antagonize NK cell internalization by reducing N-cadherin-mediated intercellular adhesion and by enhancing Rho GTPase-regulated cellular stiffness as well. Remarkably, antibody-mediated blockade of CD44 signaling potentiated the suppressive effects of NK cells on tumor growth associated with increased heterotypic CIC formation. Together, we identified CIC-mediated “in-cell killing” as a promising strategy for cancer immunotherapy.

Background: The BRAFV600E mutation is a valuable indicator for thyroid cancer diagnosis. This study aimed to develop a deep convolutional neural network (DCNN) model based on ultrasound images to predict the BRAFV600E mutation status of thyroid nodules. Methods: The ultrasound images were obtained from four hospitals between January 2017 and January 2022. We trained and validated the DCNN model based on the primary set from center 1 (979 images, 528 patients). The DCNN network consists of Conv block, Downsample block, Gaussian error linear unit, Global Average Polling, and Full Connected. The predictive performance of this model was evaluated by using areas under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity in four independent test sets from center 1 to center 4 (531 images, 282 patients). Heatmaps were used to visualize the most predictive regions of each image. Specimens obtained through fine‐needle aspiration or surgery were used to detect the BRAFV600E mutation. Results: The DCNN model achieved encouraging predictive performance by fivefold cross‐validation (AUC 0.95) in the primary set. This performance was further confirmed in the independent internal test set (AUC 0.93) and three independent external test sets (AUC 0.84–0.88). The deep learning score revealed significant differences between BRAFV600E‐mutant and BRAFV600E‐wild‐type groups (all test sets p < .001). The heatmaps visualized the most predictive region located inside or alongside the thyroid nodules. Conclusion: A DCNN model with encouraging predictive performance was developed based on ultrasound images to predict the BRAFV600E mutation status of thyroid nodules.

Abstract Senescence is believed to be a pivotal player in the onset and progression of tumors as well as cancer therapy. However, the guiding roles of senescence in clinical outcomes and therapy selection for patients with cancer remain obscure, largely due to the absence of a feasible senescence signature. Here, by integrative analysis of single cell and bulk transcriptome data from multiple datasets of gastric cancer patients, we uncovered senescence as a veiled tumor feature characterized by senescence gene signature enriched, unexpectedly, in the noncancerous cells, and further identified two distinct senescence-associated subtypes based on the unsupervised clustering. Patients with the senescence subtype had higher tumor mutation loads and better prognosis as compared with the aggressive subtype. By the machine learning, we constructed a scoring system termed as senescore based on six signature genes: ADH1B, IL1A, SERPINE1, SPARC, EZH2, and TNFAIP2. Higher senescore demonstrated robustly predictive capability for longer overall and recurrence-free survival in 2290 gastric cancer samples, which was independently validated by the multiplex staining analysis of gastric cancer samples on the tissue microarray. Remarkably, the senescore signature served as a reliable predictor of chemotherapeutic and immunotherapeutic efficacies, with high-senescore patients benefited from immunotherapy, while low-senescore patients were responsive to chemotherapy. Collectively, we report senescence as a heretofore unrecognized hallmark of gastric cancer that impacts patient outcomes and therapeutic efficacy.

ObjectivesPatients with essential tremor (ET) syndrome have more prevalent and more serious gait and balance impairments than healthy controls. In this cross-sectional study, we explored whether balance impairments are associated with falls as well as more pronounced non-motor symptoms in patients with ET syndrome.MethodsWe assessed the tandem gait (TG) test, as well as falls or near-falls that occurred over the previous year. Non-motor symptoms—including cognitive deficits, psychological and sleep disorders—were evaluated. In univariate analyses, statistical significance was corrected for multiple comparisons using the Benjamini–Hochberg method. Multiple logistic regression was utilized to evaluate the risk factors of poor TG performance in patients with ET syndrome.ResultsA total of 358 patients with ET syndrome were divided into the abnormal TG (a-TG) and normal TG (n-TG) groups based on their performances in the TG test. We revealed that 47.2% of patients with ET syndrome had a-TG. The patients with a-TG were older, were more likely female, and were more likely present with cranial tremors and falls or near-falls (all adjusted P < 0.01). The patients with a-TG had significantly lower Mini-Mental Status Examination scores, as well as significantly higher Hamilton Depression/Anxiety Rating Scale and Pittsburgh Sleep Quality Index scores. Multiple logistic regression analysis demonstrated that female sex (OR 1.913, 95% CI: 1.180–3.103), age (OR 1.050, 95% CI: 1.032–1.068), cranial tremor scores (OR 1.299, 95% CI: 1.095–1.542), a history of falls or near-falls (OR 2.952, 95% CI: 1.558–5.594), and the presence of depressive symptoms (OR 1.679, 95% CI: 1.034–2.726) were associated with the occurrence of a-TG in patients with ET syndrome.ConclusionTG abnormalities may be a predictor of fall risk in patients with ET syndrome and are associated with non-motor symptoms, especially depression.

Food safety has received unprecedented attention since the COVID-19 outbreak. Exploring food safety regulatory mechanisms in the context of cluster public crises is critical for COVID-19 prevention and control. As a result, using data from a food safety regulation survey in the Bei-jing-Tianjin-Hebei urban cluster, this paper investigates the impact of food safety regulation on the prevention and control of COVID-19. The study found that food safety regulation and cluster public crisis prevention and control have a significant positive relationship, with the ability to integrate regulatory resources acting as a mediator between the two. Second, industry groups argue that the relationship between regulatory efficiency and regulatory resource integration should be moderated in a positive manner. Finally, industry association support positively moderates the mediating role of regulatory re-source integration capacity between food safety regulatory efficiency and cluster public crises, and there is a mediating effect of being moderated. Our findings shed light on the mechanisms underlying the roles of regulatory efficiency, resource integration capacity, and industry association support in food safety, and they serve as a useful benchmark for further improving food safety regulations during the COVID-19 outbreak.

Abstract SARS-CoV-2 infection could cause severe acute respiratory syndrome, largely attributed to dysregulated immune activation and extensive lung tissue damage. However, the underlying mechanisms are not fully understood. Here, we reported that viral infection could induce syncytia formation within cells expressing ACE2 and the SARS-CoV-2 spike protein, leading to the production of micronuclei with an average rate of about 4 per syncytium (> 93%). Remarkably, these micronuclei were manifested with a high level of activation of both DNA damage response and cGAS-STING signaling, as indicated by micronucleus translocation of γH2Ax and cGAS, and upregulation of their respective downstream target genes. Since activation of these signaling pathways were known to be associated with cellular catastrophe and aberrant immune activation, these findings help explain the pathological effects of SARS-CoV-2 infection at cellular and molecular levels, and provide novel potential targets for COVID-19 therapy.

Abstract Although targeting cancer metabolism is a promising therapeutic strategy, clinical success depends on accurate molecular and metabolic subtyping. Here, this study reports two metabolism‐based molecular subtypes associated with the ketogenic treatment of colon cancer: glycolytic (glycolysis+/ketolysis−) and ketolytic (glycolysis+/ketolysis+), which are manifested by distinct profiles of metabolic enzymes and mitochondrial dysfunction, and by different responses to ketone‐containing interventions in vitro and in vivo. Notably, the glycolytic subtype is able to be transformed into the ketolytic subtype in p53‐mutated tumors upon glucose limitation, rendering resistance to ketogenic therapy associated with upregulation of ketolytic enzymes, such as OXCT1 by mutant p53. The allosteric activator of mutant p53 effectively blocks the rewired molecular expression and the reprogrammed metabolism, leading to the suppression of tumor growth. The findings highlight the utility of metabolic subtyping to guide ketogenic therapy in colon cancer and identify mutant p53 as a synthetic lethality target for ketogenic treatment.

Using tetraethoxysilane (TEOS) as a precursor, silica aerogels were synthesized via the sol-gel polymerization followed by supercritical drying process. During the polymerization period, N, N-dimethylformamide (DMF), acting as a chemical additive for the structure control, was introduced in the hydrolysis step and condensation step, respectively. As a result, the nanopore volumes for the pores smaller than 100 nm were up to 6.0 cm3/g and 5.7 cm3/g for the samples that produced with DMF addition in the hydrolysis step and condensation step, while the value for the sample without DMF was only 4.6 cm3/g. Besides, the sample with DMF addition in the condensation step possessed more uniform pore size distribution while compared with that with DMF addition in the hydrolysis step. DMF can provide a shielding layer around the colloid particles through hydrogen bonds, inhibiting the aggregation of colloid particles and the enlarging of pore sizes.

For the problem of power generation turbine blade ablation in hypersonic vehicles, hydrocarbon fuel carried by the vehicle is used to cool the turbine blades. In order to fully utilize the cooling capacity of hydrocarbon fuel, the structure of the cooling channels needs to be optimized. In this study, a variable clearance hydrocarbon fuel cooling channel is applied for the first time to the rotating turbine blades of a hypersonic vehicle to enhance the heat transfer ability of hydrocarbon fuel. The effect of clearance size on the heat transfer performance of hydrocarbon fuel under rotating conditions is investigated. The accuracy of the calculations is verified by comparison with experimental data. The results of the study show that the heat transfer performance can be significantly improved by changing the clearance of the turning section. The clearance size 2.5 D channel has the highest thermal performance with a maximum improvement of 1.8 times. The law of change of thermal performance is affected by crossing the critical temperature point, as it is different before and after the crossing. Thermal performance changes from decreasing then increasing to increasing then decreasing as the clearance size increases for high rotation speed conditions as the temperature of the entrance straddles the critical temperature. The Nusselt number first increases and then decreases for all channels with different clearance sizes with an increasing rotational speed. The friction factor changes from first increasing and then decreasing to decreasing and then increasing as the clearance size increases for high rotation speed conditions as the temperature of the entrance straddles the critical temperature.

Ram air turbines are used in the power generation systems of hypersonic vehicles, which can address the problem of the high power consumption of weapon systems. However, high incoming air temperatures can cause the turbine blades of power generation to ablate. At this point, the incoming air can no longer be used as a cooling source to cool the turbine blades. To prevent the ablation of the turbine blades of the hypersonic vehicle power generation, hydrocarbon fuel carried by the hypersonic vehicle itself is used to cool the turbine blades. Hence, hydrocarbon fuels under rotating conditions are investigated. The results show that the rotation leads to a strong pressure gradient that causes the density and dynamic viscosity of hydrocarbon fuel to increase dramatically. Compared to the static condition, the density and dynamic viscosity of the hydrocarbon fuel increase by a maximum of 65.1% and 405%, respectively, under the rotating condition. This leads to an obvious reduction in velocity. The comprehensive influence of the physical properties of the fuel, centrifugal force, and Coriolis force causes the convective heat transfer coefficient and Nusselt number of the channel to first increase and then decrease with the increase in the rotational speed. Compared to the static condition, the convective heat transfer coefficient and Nusselt number increase by a maximum of 69.7% and 45.6%, respectively, under the rotating condition. The critical rotational speed of the Nusselt number from rise to fall is 20,000 rpm for different inlet temperature conditions.

With the number of Internet of Things devices continually increasing, the endogenous security of Internet of Things communication systems is growingly critical. Physical layer authentication is a powerful means of resisting active attacks by exploiting the unique characteristics inherent in wireless signals and physical devices. Many existing physical layer authentication schemes usually assume physical layer attributes obey certain statistical distributions that are unknown to receivers. To overcome the uncertainty, machine learning–based authentication approaches have been employed to implement threshold-free authentication. In this article, we utilize an expectation–conditional maximization algorithm to provide the physical layer attribute estimates required for the authentication phase and a logistic regression model to achieve threshold-free physical layer authentication. Moreover, a Frank–Wolfe algorithm is considered to achieve fast convergence of the logistic regression parameters and multi-attributes are adopted to increase the differentiation of transmitters. Simulation results demonstrate that the obtained attribute estimates are sufficient to provide a reliable source of data for authentication and the proposed threshold-free multi-attributes physical layer authentication scheme can effectively improve authentication accuracy, with the false alarm rate P f reduced to 0.0263% and the miss detection rate P m reduced to 0.3466%.

HIF1alpha is reported to drive tumourigenesis through activating glycolysis. Here, the authors show that HIFAL, the HIF1alpha antisense long non-coding RNA, and HIF1alpha form a positive feed-forward loop which is essential for HIF1a-mediated metabolic reprogramming and oncogenic role.

Taxanes represented by paclitaxel and targeted therapy including trastuzumab are two common agents for human epidermal growth factor receptor-2 (HER-2)-positive breast cancer patients. Effectiveness, however, usually comes at the cost of many side effects, some of which are even fatal. Drug-induced interstitial lung diseases (DILDs) comprise a group of drug-induced pulmonary injuries usually caused by using these medications. For DILDs, systemic therapy can be harmful to lung tissues and rapidly threaten the lives of some breast cancer patients. Through the cases from our hospital and related studies in medical databases, we hope readers can learn a lesson from an angle of multi-disciplinary integration based on clinical practice and pharmacological mechanisms to make anti-cancer agents less harmful and reduce the incidence of DILD in breast cancer patients during systemic therapy.

Although peripheral venous blood biomarkers are related to respiratory function in Amyotrophic lateral sclerosis (ALS) patients, there are still few prediction models that predict pulmonary function. This study aimed to investigate the venous blood biomarkers associated with respiratory function in patients with ALS from southwest China and to create prediction models based on those clinical biomarkers using logistic regression. A total of 319 patients with ALS from the retrospective cohort and 97 patients with ALS from the prospective cohort were enrolled in this study. A multivariable prediction model for the correlation between peak expiratory flow (PEF) and hematologic, biochemical laboratory parameters, and clinical factors in patients with ALS was created. Along with female patients, bulbar-onset, lower body mass index (BMI), later age of onset, lower level of creatinine, uric acid, triglyceride, and a higher level of high-density lipoprotein cholesterol (HDL_C) were related to reduced PEF. The area under the receiver operating characteristics (ROC) curve is.802 for the test set and.775 for the validation set. The study constructed a multivariable prediction model for PEF in patients with ALS. The results can be helpful for clinical practice to predict respiratory impairment.

The human epidermal growth factor receptor-2 (ERBB2; formerly HER2)isoform ERBB2ΔEx16 (ERBB2d16) was oncogenic by mediating epithelial-mesenchymal transition (EMT), immune evasion, and resistance cell death to the anti-HER2 (trastuzumab) therapy. However, its physiological implications in gastric cancer were unclear. In this study, we examined a total of 110 patients with either locally advanced or metastatic HER2+ gastric cancer for the expression of ERBB2d16 and EMT markers, and the infiltration of CD3+ T cells in tumor tissues, and evaluated their relevance with the responses to the standard chemotherapy plus trastuzumab according to the RECIST criteria. We found that the ERBB2d16 isoform was present at a relatively high level in about half of the tumor samples examined (53/110) and an elevated ERBB2d16/ERBB2 ratio was positively associated with the expression of high E-cadherin and low vimentin indicating EMT, and with poor CD3+ T cell infiltration and strong intratumoral expression of programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) as well as reduced diversity of T cell receptor clones. Moreover, the progression-free survival and overall survival of patients treated with trastuzumab were substantially shorter in those with a high ERBB2d16/ERBB2 ratio. In agreement, analysis by Cox proportional hazards models confirmed that high ERBB2d16 expression was a risk factor associated with an adverse prognosis. Thus, our data fit well with an oncogenic role of ERBB2d16 in gastric cancer by promoting EMT and immunosuppression. We also found that ERBB2d16 expression resists gastric cell death in patients treated with trustuzumab, and the ERBB2d16/ERBB2 ratio may serve as a novel prognostic maker for patients with gastric cancer that receive trastuzumab therapy.

ObjectiveMetastatic spinal dissemination (MSD) of supratentorial glioma is very rare and there is no established standard of care. The current study investigates the clinical characteristics and course of spinal dissemination of supratentorial glioma.MethodsA retrospective analysis of adult patients with MSD of supratentorial glioma treated in the Department of Oncology in Beijing Shijitan Hospital, Capital Medical University from June 2012 until August 2021 was performed. The time to event was estimated using Kaplan–Meier analysis. Univariate analyses were performed using log-rank test and multivariate analysis was performed using the Cox proportional hazards model.ResultsThirty-four adult patients with MSD of supratentorial glioma were enrolled in this retrospective study. The median time to MSD (TTMSD) and overall survival (OS) were 5 months (range: 0–78 months) and 15 months (range: 0.7–85 months), respectively, in the entire cohort. Univariate analysis demonstrated that the patients who had received TMZ therapy had a longer TTMSD than those who did not (mTTMSD: 15 vs. 3 months, log-rank P = 0.0004). Furthermore, a protracted duration of salvage chemotherapy of >6 months after MSD was associated with longer OS of the patients with MSD of supratentorial glioma (mOS: 13 vs. 5 months, log-rank P = 0.0163) and reduced the death risk by 64.3% (hazard ratio: 0.357, 95% CI: 0.141–0.901, P = 0.029) compared with a duration ≤6 months.ConclusionPatients with MSD of supratentorial glioma experienced poor prognosis and adjuvant chemotherapy may delay the occurrence of MSD. The protracted duration of systemic salvage chemotherapy may favor survival after spinal dissemination.

Cell-in-cell (CIC) structures are defined as the special structures with one or more cells enclosed inside another one. Increasing data indicated that CIC structures were functional surrogates of complicated cell behaviors and prognosis predictor in heterogeneous cancers. However, the CIC structure profiling and its prognostic value have not been reported in human esophageal squamous cell Carcinoma (ESCC). We conducted the analysis of subtyped CIC-based profiling in ESCC using “epithelium-macrophage-leukocyte” (EML) multiplex staining and examined the prognostic value of CIC structure profiling through Kaplan-Meier plotting and Cox regression model. Totally, five CIC structure subtypes were identified in ESCC tissue and the majority of them was homotypic CIC (hoCIC) with tumor cells inside tumor cells (TiT). By univariate and multivariate analyses, TiT was shown to be an independent prognostic factor for resectable ESCC, and patients with higher density of TiT tended to have longer post-operational survival time. Furthermore, in subpopulation analysis stratified by TNM stage, high TiT density was associated with longer overall survival (OS) in patients of TNM stages III and IV as compared with patients with low TiT density (mean OS: 51 vs 15 months, P = 0.04) and T3 stage (mean OS: 57 vs 17 months, P=0.024). Together, we reported the first CIC structure profiling in ESCC and explored the prognostic value of subtyped CIC structures, which supported the notion that functional pathology with CIC structure profiling is an emerging prognostic factor for human cancers, such as ESCC.

Allium hookeri is a rare medicinal plant with unique flavor. In this study, the first complete chloroplast (cp) genome of A. hookeri was sequenced and assembled based on the next generation sequencing. The cp genome is 153,592 bp in length, including a large single-copy (LSC) region of 82,609 bp, a small single-copy (SSC) region of 17,487 bp, and a pair of inverted repeat (IR) regions of 26,748 bp each. The genome encodes 131 genes, including 86 protein-coding genes, 39 tRNA genes, and six rRNA genes. The GC content of whole genome is 36.99%. The phylogenetic analysis based on 24 complete cp sequences revealed that A. hookeri was at the base of the phylogenetic tree, indicating an older species in the Allium genus.

Euchresta tubulosa Dunn not only is a national second-level protected wild plant in China, but also has a long history as a source plant in traditional Chinese medicine. The chloroplast (cp) genome of E. tubulosa was 154,102 bp, consisting of a large single-copy region (LSC: 92,877 bp), a small single-copy region (SSC: 36,645 bp), and a pair of inverted repeat regions (IRb and Ira: 12,290 bp, respectively). These sequences encoded 123 genes, including 78 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The phylogenetic analysis showed that E. tubulosa is close to Lupinus species.

Chimonobambusa quadrangularis (Fenzl) Makino is one of the ‘Square Bamboo’ due to its square-shaped culm. However, as an edible bamboo, there is no genomic information reported so far. In this study, we reported and characterized the first plastome of C. quadrangularis based on Illumina Hiseq sequencing. The plastome exhibited a typical angiosperm circular structure, containing four regions: large single-copy region (LSC: 83,125 bp), small single-copy region (SSC: 12,811 bp), and a pair of inverted repeat regions (IR: 21,802 bp). The plastome consisted of 139,540 bp in size, with 82 protein-coding genes, 39 tRNA genes, and eight rRNA genes. The total nucleotide composition consisted of 30.16% A, 30.97% T, 19.25% C, and 19.63% G. The G + C content of the whole plastome was 38.88%. Phylogenetic analysis based on the complete plastomes of six species indicated that C. quadrangularis was closed to C. hejiangensis. The plastome is helpful for studying the evolution of beneficial adaptations and developing bioremediation and biomedical science.

Objective. To investigate the differences of candidate cerebrospinal fluid (CSF) biomarkers associated with multiple system atrophy (MSA) and Parkinson’s disease (PD). Method. Here, a systematic review and meta-analysis were conducted on studies related to CSF biomarkers associated with MSA and PD obtained from PubMed, Web of Science, Embase, and Cochrane databases. Data were pooled where appropriate and used to calculate standardized mean differences (SMDs) with 95% confidence intervals (CI). Heterogeneity was assessed using the I2 statistic while Egger’s test was used to test for existing publication bias. Results. MSA patients had higher CSF t-tau (SMD=0.41, 95% CI: 0.10 to 0.72) and YKL-40 (SMD=0.63, 95% CI 0.12 to1.15) as well as DJ-1 (SMD=1.05, 95% CI 0.67 to 1.42) levels than PD patients, while CSF p-tau (SMD=−0.17, 95% CI, -0.31 to -0.02) and Aβ-42 (SMD=−0.33, 95% CI, -0.55 to -0.12) levels in MSA patients were lower than those in PD patients. There were no differences in CSF’s GFAP and Flt3 ligand levels in both MSA and PD patients. Conclusion. The study revealed the differences in CSF biomarker levels between MSA and PD cohorts that can be further explored to clinically distinguish MSA from PD.

In this paper, the flow and heat dissipation performance of 0.1–0.5 vol per cent of Al2O3 -water nanofluid through serpentine micro-channel was experimentally studied in the Reynolds range 124–1000. By analyzing the experimental results of nanofluid flow and heat dissipation: In the experiment, the Nusselt number of nanofluids is 1.12–1.66 times that of deionized water, which indicates that Al2O3 -water nanofluids have significant heat transfer enhancement effect. Nanofluid flow resistance is 1.02–1.80 times that of deionized water, this indicates that Al2O3 -water nanofluid has the disadvantage of increasing energy consumption. From a comprehensive performance point of view: all the nanofluids used in the experiment have enhanced heat transfer factors more significant than one, and the enhanced heat transfer effect is better than that of deionized water, this suggests that Al2O3 -water nanofluid has the drawback of rising energy consumption. All the nanofluids used in the experiment have enhanced heat transfer factors more significant than one, and the enhanced heat transfer effect is better than that of deionized water. Nano-fluids, with a volume fraction of 0.4%, have an average increased heat transfer factor of 1.4, which is the best overall performance.

Summary: The cellular targets of SARS-CoV-2, the novel coronavirus causing the COVID-19 pandemic, is still rudimentary. Here, we incorporated the protein information to analyze the expression of ACE2, the SARS-CoV-2 receptor, together with co-factors, TMPRSS2 and Furin, at single-cell level in situ, which we called protein-proofed single-cell RNA (pscRNA) profiling. Systemic analysis across 36 tissues revealed a rank list of candidate cells potentially vulnerable to SARS-CoV-2. The top targets are lung AT2 cells and macrophages, then cardiomyocytes and adrenal gland stromal cells, followed by stromal cells in testis, ovary, and thyroid, whereas the kidney proximal tubule cells, cholangiocytes, and enterocytes are less likely to be the primary SARS-CoV-2 targets. Actually, the stomach may constitute a physical barrier against SARS-CoV-2 as the acidic environment (pH < 2.0) could completely inactivate SARS-CoV-2 pseudo-viruses. Together, we provide a comprehensive view on the potential SARS-CoV-2 targets by pscRNA profiling.

Background Endometriosis (EMs) is a non-malignant gynecological disease, whose pathogenesis remains to be clarified. Recent studies have found that hypoxia induces epithelial-mesenchymal transition (EMT) as well as epigenetic modification in EMs. However, the relationship between EMT and demethylation modification under hypoxia status in EMs remains unknown. Methods The expression of N-cadherin, E-cadherin and TET1 in normal endometria, eutopic endometria and ovarian endometriomas was assessed by immunohistochemistry and immunofluorescence double staining. 5-hmC was detected by fluorescence-based ELISA kit using a specific 5-hmC antibody. Overexpression and inhibition of TET1 or hypoxia-inducible factor 2α (HIF-2α) were performed by plasmid and siRNA transfection. The expression of HIF-2α, TET1 and EMT markers in Ishikawa (ISK) cells (widely used as endometrial epithelial cells) was evaluated by western blotting. The interaction of HIF-2α and TET1 was analyzed by chromatin immunoprecipitation. Results Demethylation enzyme TET1 (ten-eleven translocation1) was elevated in glandular epithelium of ovarian endometrioma, along with the activation of EMT (increased expression of N-cadherin, and decreased expression of E-cadherin) and global increase of epigenetic modification marker 5-hmC(5-hydroxymethylcytosine). Besides, endometriosis lesions had more TET1 and N-cadherin co-localized cells. Further study showed that ISK cells exhibited enhanced EMT, and increased expression of TET1 and HIF-2α under hypoxic condition. Hypoxia-induced EMT was partly regulated by TET1 and HIF-2α. HIF-2α inhibition mitigated TET1 expression changes provoked by hypoxia. Conclusions Hypoxia induces the expression of TET1 regulated by HIF-2α, thus may promote EMT in endometriosis.

The high efficiency multi-staged plasma (HEMP) thruster, also known as the cusped field thruster, becomes a candidate microthruster of new generation space observation missions for its low complexity and potential long life over a wide range of thrust. Since there is a lack of relevant research of the wall material effects on the HEMP thruster, a low-power HEMP thruster with three different dielectric wall materials is tested to discover the effects on performance and discharge characteristics. A Faraday probe, a retarding potential analyzer, and a Langmuir probe are employed to diagnose the plume, and the plasma behavior differences in ionization and acceleration processes are indicated. The result shows that the secondary electron emission coefficient of the wall material has definite effects under a low mass flow rate, which is similar to the effects on the Hall thrusters, but no distinct difference is found in high flow rate conditions.

Summary: Entosis is a cell-in-cell (CIC)-mediated death program. Contractile actomyosin (CA) and the adherens junction (AJ) are two core elements essential for entotic CIC formation, but the molecular structures interfacing them remain poorly understood. Here, we report the characterization of a ring-like structure interfacing between the peripheries of invading and engulfing cells. The ring-like structure is a multi-molecular complex consisting of adhesive and cytoskeletal proteins, in which the mechanical sensor vinculin is highly enriched. The vinculin-enriched structure senses mechanical force imposed on cells, as indicated by fluorescence resonance energy transfer (FRET) analysis, and is thus termed the mechanical ring (MR). The MR actively interacts with CA and the AJ to help establish and maintain polarized actomyosin that drives cell internalization. Vinculin depletion leads to compromised MR formation, CA depolarization, and subsequent CIC failure. In summary, we suggest that the vinculin-enriched MR, in addition to CA and AJ, is another core element essential for entosis.

Though homotypic cell-in-cell (hoCIC) structures are implicated in the development and progression of multiple human tumors, the molecular mechanisms underlying their formation remain poorly understood. We found that the expression of Protocadherin-7 (PCDH7), an integral membrane protein, was negatively associated with the formation of hoCIC structures. Overexpression of PCDH7 efficiently inhibits, while its depletion significantly enhances, hoCIC formation, which was attributed to its regulation on intercellular adhesion and contractile actomyosin as well. Via directly interacting with and inactivating PP1α, a protein phosphatase that dephosphorylates pMLC2, PCDH7 increases the level of pMLC2 leading to enhanced actomyosin at the intercellular region and compromised hoCIC formation. Remarkably, PCDH7 enhanced anchorage-independent cell growth in a hoCIC-dependent manner. Together, we identified PCDH7 as the first trans-membrane protein that inhibits hoCIC formation to promote tumor growth.

Detection of the vitality of wounds is essential in forensic practice. The present study used Illumina RNA-seq technology to determine gene expression profiles in contused mouse skin. In obtained high quality sequencing reads, the reads were mapped onto a reference transcriptome (Mus_musculus.GRCm38.83). The results revealed that there were 659 up-regulated and 996 down-regulated differentially expressed genes (DEGs) in contused mouse skin. The DEGs were further analyzed using the Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes databases. Genes from different functional categories and signalling pathways were enriched, including the immune system process, immune response, defense response, cytokine–cytokine receptor interaction, complement and coagulation cascades and chemokine signalling pathway. Expression patterns of 11 DEGs were verified by RT-qPCR in mice skins. In addition, alterations of five DEGs were also analyzed in postmortem human wound samples. The results were in concordance with the results of RNA-seq. These findings suggest that RNA-seq is a powerful tool to reveal DEGs as potential markers for vital reaction in terms of forensic practices.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) syndrome, caused by mutations in the thymidine phosphorylase gene, manifests as a multisystemic disorder characterized by severe gastrointestinal dysmotility, cachexia, ptosis and ophthalmoparesis, peripheral neuropathy, and leukoencephalopathy. These clinical manifestations, with the exception of leukoencephalopathy, are mimicked by MNGIE-like syndrome, linked to polymerase-gamma (POLG) gene. Here, we report a 49-year-old Chinese man with MNGIE-like syndrome involved leukoencephalopathy and was associated with novel POLG mutations. This case expands the clinical spectrum of MNGIE-like syndrome.

In recent years, bariatric surgery has emerged as a promising treatment for type 2 diabetes. Bariatric surgery is known to cause alterations in the relative abundance and composition of gut microbiota, which may lead to alterations in the levels of Short-Chain Fatty Acids (SCFAs) that are produced during fermentation by gut microbes. However, little is known about the mechanism of improved glucose metabolism mediated by gut microbiota following bariatric surgery. The aim of our study was to explore whether changes in gut microbiota and in fecal SCFA could be detected following single-anastomosis duodenal jejunal bypass (DJB-sa) surgery, a type of bariatric surgery, and whether these alterations might be related to the improvement of glucose metabolism. To this end, we performed DJB-sa or SHAM surgery on Goto-Kakisaki (GK) rats. We then compared the glucose metabolism as well as changes in gut microbiota and SCFAs levels between both groups. Our results showed that DJB-sa surgery was associated with a significant decrease in fasting blood glucose (FBG), intraperitoneal glucose tolerance test (IPGTT), and fasting serum insulin (FSI). And, DJB-sa led to a change in the composition of gut microbiota including an increase in the relative abundance of SCFA-producing bacteria (Bifidobacterium and Subdoligranulum). Moreover, the levels of six SCFAs in feces, as well as the intestinal expression of SCFA receptors including G-protein-coupled receptor 41 (GPR41), G-protein-coupled receptor 43 (GPR43), and G-protein-coupled receptor 109A (GPR109A), and the expression of Glucagon-like peptide-1 (GLP-1) displayed a significant increase following DJB-sa compared with the Sham group. Thus, the gut microbiota may contribute to the improvement of glucose metabolism in type 2 diabetes following DJB-sa. In conclusion, our study shows that DJB-sa improves glucose metabolism by modulating gut microbiota and by increasing short-chain fatty acid production.