Highly stereoselective α-glycosylation with GalN3 donors enabled collective synthesis of mucin-related tumor associated carbohydrate antigens.

Mucin-related tumor-associated carbohydrate antigens (TACAs) are important and interesting targets for cancer vaccine therapy. However, efficient access to a library of mucin-related TACAs remains a challenging task. One of the key issues is the challenging construction of α-GalNAc linkages. Here, we report highly stereoselective α-glycosylation with GalN3N-phenyl trifluoroacetimidate donors, which features excellent yields, outstanding stereoselectivities, broad substrate scope and mild reaction conditions. This method is successfully applied to highly stereoselective synthesis of GalN3-α-O-Ser, which served as the common intermediate for collective synthesis of a wide range of TACAs including TN antigen, STN antigen, 2,6 STF antigen, 2,3 STF antigen, glycophorin and cores 1-8 mucin-type O-glycans. In particular, the rationale for this highly stereoselective α-glycosylation is provided for the first time using DFT calculations and mechanistic studies, highlighting the crucial roles of reagent combinations (TMSI and Ph3PO) and the H-bonding directing effect of the N3 group.

Virome survey of the bat, Rhinolophus affinis, in Hainan Province, China.

Bats are important mammal reservoirs of zoonotic pathogens. However, due to research limitations involving species, locations, pathogens, or sample types, the full diversity of viruses in bats remains to be discovered. We used next-generation sequencing technology to characterize the mammalian virome and analyze the phylogenetic evolution and diversity of mammalian viruses carried by bats from Haikou City and Tunchang County in Hainan Province, China. We collected 200 pharyngeal swab and anal swab samples from Rhinolophus affinis, combining them into nine pools based on the sample type and collection location. We subjected the samples to next-generation sequencing and conducted bioinformatics analysis. All samples were screened via specific PCR and phylogenetic analysis. The diverse viral reads, closely related to mammals, were assigned into 17 viral families. We discovered many novel bat viruses and identified some closely related to known human/animal pathogens. In the current study, 6 complete genomes and 2 partial genomic sequences of 6 viral families and 8 viral genera have been amplified, among which 5 strains are suggested to be new virus species. These included coronavirus, pestivirus, bastrovirus, bocavirus, papillomavirus, parvovirus, and paramyxovirus. The primary finding is that a SADS-related CoV and a HoBi-like pestivirus identified in R. affinis in Hainan Province could be pathogenic to livestock. This study expands our understanding of bats as a virus reservoir, providing a basis for further research on the transmission of viruses from bats to humans.

MORN2 regulates the morphology and energy metabolism of mitochondria and is required for male fertility in mice.

BACKGROUND: Mitochondria produce adenosine triphosphate through respiratory activities to power sperm differentiation and motility, and decreased mitochondrial respiratory activity can result in poor sperm motility and asthenospermia. The mitochondrial sheath is a component of the mid-piece of the sperm flagellum, and dysfunction of the sheath can reduce sperm motility and cause male infertility. The membrane occupation and recognition nexus-motif protein 2 (MORN2) is testis enriched in mice, and the MORN motif was reported to play a role in the regulation of bioelectrical signal homeostasis in cardiomyocytes. METHODS: We generated Morn2-/- mice using CRISPR/Cas9 and evaluated the potential functions of MORN2 in spermiogenesis through histological analysis, fertility examination, RT-PCR, CASA, immunofluorescence, TUNEL, electron microscopy analysis, mitochondrial energy metabolism analysis, etc. RESULTS: The Morn2-/- mice were infertile, and their sperm showed severe motility defects. Morn2-/- sperm also had abnormal morphology characterized by bent heads, aberrant mitochondrial sheath formation, lower mitochondrial membrane potential, higher levels of reactive oxygen species, and decreased mitochondrial respiratory activity. CONCLUSIONS: Our study demonstrates that MORN2 is essential for male fertility and indicates that MORN2 functions in mitochondrial sheath formation and regulates mitochondrial respiratory activity.

A model based on immunogenic cell death-related genes predicts prognosis and response to immunotherapy in kidney renal clear cell carcinoma.

Background: The prognosis of patients with kidney renal clear cell carcinoma (KIRC), a life-threatening condition, is poor. Immunogenic cell death (ICD) induces regulated cell death via immunogenic signal secretion and exposure. ICD induces regulated cell death through immunogenic signal secretion and exposure. ICD plays an essential role in tumorigenesis, however, the role of ICD in KIRC remains unclear. Methods: This study examined the expression levels of 34 ICD-related genes in The Cancer Genome Atlas (TCGA) data set. Signature genes linked to KIRC survival were identified using Cox regression. Next, a prognostic risk model (RM) was built. Subsequently, the KIRC patients were divided into low- and high-risk groups. Kaplan-Meier curves and receiver operating characteristic (ROC) curves were plotted. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were carried out to investigate the possible role of differential gene expression between the two groups. The immune microenvironment (IME) was assessed using Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression, CIBERSORT, and single-sample gene-set enrichment analysis algorithms. An enrichment analysis was used to determine the biological significance of these regulatory networks we conducted. The relationship between immune checkpoint gene expression and risk score, and the relationship between treatment outcome and gene expression were assessed using correlation analyses. Results: We developed a KIRC RM based on five ICD-related genes (i.e., FOXP3, IFNB1, IL6, LY96, and TLR4), which were identified as the prognostic signature genes. Using the TCGA data set, we conducted a survival analysis and found that the 3-year RM had an area under the curve (AUC) of 0.735, which validated the reliability of the signature. Similarly, using the International Cancer Genome Consortium (ICGC) data set, we found that the 3-year RM had an AUC of 0.732. Conclusions: A RM based on five ICD-related genes was built to predict the prognosis of KIRC patients. This RM predicted patient prognosis and reflected the tumor IME of KIRC patients. Thus, this RM could be used to promote individualized treatments and provide potential novel targets for immunotherapy.

Association between intracranial aneurysm wall enhancement and intracranial atherosclerotic plaque: a cross-sectional study using high-resolution vessel wall imaging.

Background: Intracranial aneurysms and intracranial atherosclerosis are prevalent cerebrovascular diseases, and individuals with atherosclerosis have a higher incidence of aneurysms than those without atherosclerosis. However, few studies have conducted combined analyses to investigate the potential association between intracranial aneurysms and intracranial atherosclerosis. This retrospective cross-sectional study aimed to investigate the association between the characteristics of the aneurysm wall and intracranial large arterial plaque using high-resolution vessel wall imaging (HR-VWI). Methods: Hospitalized patients diagnosed with anterior circulation unruptured intracranial aneurysms (UIAs), who were diagnosed at Huashan Hospital of Fudan University in Shanghai, China, between March 2016 to February 2018, were consecutively recruited for this study. The patients' pre-treatment HR-VWI images and 3D time-of-flight magnetic resonance angiography (3D-TOF-MRA) images were collected. The patients and UIAs were divided into two groups according to the presence or absence of plaque in the M1 segment of the middle cerebral artery (MCA). Clinical information and aneurysm characteristics were compared between the two groups. Aneurysm wall enhancement (AWE) and M1 plaque were graded on scales of 0 to 2 on HR-VWI. Based on the gradings, the correlation between AWE and the M1 plaques was analyzed. Results: A total of 109 patients with 128 saccular UIAs in the anterior circulation were enrolled in the study. Of the patients, there were 56 patients (with 65 UIAs) in the group with M1 plaque and 53 patients (with 63 UIAs) in the group without plaque. There were significant differences between the two groups in terms of both their clinical information (age and hypertension) and aneurysm characteristics (AWE pattern and AWE degree). The grades of the AWE patterns and the AWE degrees of the UIAs were higher in the group with M1 plaque than in the group without plaque. In the M1 plaque group, the grade of M1 plaque was positively correlated with the grade of AWE pattern (correlation coefficient R=0.41, P=0.001) and the grade of AWE degree (correlation coefficient R=0.50, P<0.001). Conclusions: MCA atherosclerosis plaque was associated with the AWE of saccular aneurysms. When evaluating UIAs, attention should also be paid to the large arterial wall, which may assist in assessing the stability of the aneurysm and enable better decision making.

Construction and validation of a novel NAD+ metabolism-related risk model for prognostic prediction in osteosarcoma.

Currently, the prognosis of osteosarcoma (OS) remains discouraging, especially in elderly/metastatic OS patients. By impairing the antitumor effect of immune cells, tumor immune microenvironment (TIME) provides an environment conducive to tumor proliferation, which highly requires accelerated nicotinamide adenine dinucleotide (NAD+) metabolism for energy. Recently, many genes involved in the sustained production of NAD+ in malignant tumors have been verified to be possible prognostic indicators and therapeutic targets. Therefore, the current study was to probe into the association of NAD+ metabolism-related genes with TIME, immunotherapeutic response, and prognosis in OS. All OS data for the study were acquired from TARGET and GEO databases. In bioinformatics analysis, we performed Cox analysis, consensus clustering, principal component analysis, t-distributed stochastic neighbor embedding, uniform manifold approximation and projection, gene set enrichment analysis, gene set variation analysis, Lasso analysis, survival and ROC curves, nomogram, immune-related analysis, drug sensitivity analysis, and single-cell RNA sequencing (scRNA-seq) analysis. Cell transfection assay, RT-qPCR, western blot analysis, as well as cell wound healing, migration, and invasion assays were performed in vitro. Bioinformatics analysis identified A&B clusters and six NAD+ metabolism-related differentially expressed genes, constructed risk model and nomogram, and performed immune-related analysis, drug susceptibility analysis, and scRNA-seq analysis to inform the clinical treatment framework. In vitro experiment revealed that CBS and INPP1 can promote migration, proliferation as well as invasion of OS cells through TGF-ß1/Smad2/3 pathway. Based on bioinformatics analysis and in vitro validation, this study confirmed that NAD+ metabolism affects TIME to suggest the prognosis of OS.

Luteolin suppresses oral carcinoma 3 (OC3) cell growth and migration via modulating polo-like kinase 1 (PLK1) expression and cellular energy metabolism. / æœ¨çŠ€è‰ç´ é€šè¿‡è°ƒèŠ‚PLK1è¡¨è¾¾å’Œç»†èƒžèƒ½é‡ä»£è°¢æŠ‘åˆ¶å£è ”ç™Œç»†èƒžOC3的生长和迁移.

Oral squamous cell carcinoma (OSCC) is a prevalent malignant tumor affecting the head and neck region (Leemans et al., 2018). It is often diagnosed at a later stage, leading to a poor prognosis (Muzaffar et al., 2021; Li et al., 2023). Despite advances in OSCC treatment, the overall 5-year survival rate of OSCC patients remains alarmingly low, falling below 50% (Jehn et al., 2019; Johnson et al., 2020). According to statistics, only 50% of patients with oral cancer can be treated with surgery. Once discovered, it is more frequently at an advanced stage. In addition, owing to the aggressively invasive and metastatic characteristics of OSCC, most patients die within one year of diagnosis. Hence, the pursuit of novel therapeutic drugs and treatments to improve the response of oral cancer to medication, along with a deeper understanding of their effects, remains crucial objectives in oral cancer research (Johnson et al., 2020; Bhat et al., 2021; Chen et al., 2023; Ruffin et al., 2023).

Overview of research progress on the association of dietary potassium intake with serum potassium and survival in hemodialysis patients, does dietary potassium restriction really benefit hemodialysis patients?

For the general population, increasing potassium intake can reduce the incidence of cardiovascular and cerebrovascular diseases. However, since hyperkalemia is a common and life-threatening complication in maintenance hemodialysis patients, which can increase the risk of malignant arrhythmia and sudden death, the current mainstream of management for hemodialysis patients is dietary potassium restriction in order to prevent hyperkalemia. Hemodialysis patients are usually advised to reduce dietary potassium intake and limit potassium-rich fruits and vegetables, but there is limited evidence to support this approach can reduce mortality and improve quality of life. There is still no consistent conclusion on the association between dietary potassium intake and serum potassium and survival in hemodialysis patients. According to the current small observational studies, there was little or even no association between dietary potassium intake and serum potassium in hemodialysis patients when assurance of adequate dialysis and specific dietary patterns (such as the plant-based diet mentioned in the article) are being followed, and excessive dietary potassium restriction may not benefit the survival of hemodialysis patients. Additionally, when assessing the effect of diet on serum potassium, researchers should not only focus on the potassium content of foods, but also consider the type of food and the content of other nutrients. However, more large-scale, multi-center clinical trials are required to provide high-quality evidence support. Besides, further research is also needed to determine the optimal daily potassium intake and beneficial dietary patterns for hemodialysis patients.

Co-option of a non-retroviral endogenous viral element in planthoppers.

Non-retroviral endogenous viral elements (nrEVEs) are widely dispersed throughout the genomes of eukaryotes. Although nrEVEs are known to be involved in host antiviral immunity, it remains an open question whether they can be domesticated as functional proteins to serve cellular innovations in arthropods. In this study, we found that endogenous toti-like viral elements (ToEVEs) are ubiquitously integrated into the genomes of three planthopper species, with highly variable distributions and polymorphism levels in planthopper populations. Three ToEVEs display exon‒intron structures and active transcription, suggesting that they might have been domesticated by planthoppers. CRISPR/Cas9 experiments revealed that one ToEVE in Nilaparvata lugens, NlToEVE14, has been co-opted by its host and plays essential roles in planthopper development and fecundity. Large-scale analysis of ToEVEs in arthropod genomes indicated that the number of arthropod nrEVEs is currently underestimated and that they may contribute to the functional diversity of arthropod genes.

Identification of lncRNAs associated with uterine corpus endometrial cancer prognosis based on the competing endogenous RNA network.

Uterine Corpus Endometrial Carcinoma (UCEC) is one of the major malignant tumors of the female reproductive system. However, there are limitations in the currently available diagnostic approaches for UCEC. Long non-coding RNAs (lncRNAs) play important roles in regulating biological processes as competitive endogenous RNA (ceRNA) in tumors. To study the potential of lncRNAs as non-invasive diagnostic tumor markers, RNA-sequencing dataset of UCEC patients from The Cancer Genome Atlas was used to identify differentially expressed genes. A lncRNA-miRNA-mRNA ceRNA network was constructed by differentially expressed lncRNAs, miRNAs and miRNAs. Pathway enrichment and functional analysis for the mRNAs in the constructed ceRNA network provide the direction of future research for UCEC by demonstrating the most affected processes and pathways. Seven potential lncRNA biomarkers (C20orf56, LOC100144604, LOC100190940, LOC151534, LOC727677, FLJ35390, LOC158572) were validated in UCEC patients by quantitative real-time PCR. Notably, LOC100190940 and LOC158572 were identified as novel RNA molecules with unknown functions. Receiver operating characteristic (ROC) curve analysis demonstrated that the combined 7 lncRNAs had a high diagnostic value for UCEC patients with area under curve (AUC) of 0.941 (95% CI: 0.875-0.947). Our study highlights the potential of the validated 7 lncRNAs panel as diagnostic biomarkers in UCEC, providing new insights into the UCEC pathogenesis.

Neuroprotective Effects of Human-Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cell Extracellular Vesicles in Ischemic Stroke Models.

BACKGROUND: Stroke represents the second leading cause of death and the primary cause of long-term disability in humans. The transplantation of mesenchymal stem cells (MSC) reportedly improves functional outcomes in animal models of cerebral ischemia. Here, we evaluate the neuroprotective potential of extracellular vesicles secreted from human-induced pluripotent stem cell-derived mesenchymal stem cells (hiPS-MSC-EV) using preclinical cell-based and animal-based models of ischemic strokes. METHODS: hiPS-MSC-EV were isolated using an ultrafiltration method. HT22 cells were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) injury for 2 h, followed by treatment with hiPS-MSC-EV (100 µg/mL). Male C57BL/6 mice were subjected to middle cerebral artery occlusion (MCAO) followed by an intravenous injection of hiPS-MSC-EV (100 µg) at three distinct time points. RESULTS: Our experimental approach revealed hiPS-MSC-EV promoted HT22 cell proliferation, reduced apoptosis, and altered cellular morphology following OGD/R. In addition, hiPS-MSC-EV reduced the volume of infarcts, improved spontaneous movement abilities, and enhanced angiogenesis by expressing the VEGF and CXCR4 proteins in the infarcted hemisphere of the MCAO-treated mouse model. CONCLUSION: Our findings provide evidence of the potential neuroprotective effects of hiPS-MSC-derived extracellular vesicles (hiPS-MSC-EVs) in both in vitro and in vivo mouse models of ischemic stroke. These results suggest that hiPS-MSC-EVs may play a role in neurorestoration and offer insights into potential cell-free strategies for addressing cerebral ischemia.

C1GalT1 expression reciprocally controls tumour cell-cell and tumour-macrophage interactions mediated by galectin-3 and MGL with double impact on cancer development and progression.

Although most cell membrane proteins are modified by glycosylation, our understanding of the role and actions of protein glycosylation is still very limited. ß1,3galactosyltransferase (C1GalT1) is a key glycosyltransferase that controls the biosynthesis of the Core 1 structure of O-linked mucin type glycans and is overexpressed by many common types of epithelial cancers. This study reports that suppression of C1GalT1 expression in human colon cancer cells caused substantial changes of protein glycosylation of cell membrane proteins, many of which were ligands of the galactoside-binding galectin-3 and the macrophage galactose-type lectin (MGL). This led to significant reduction of cancer cell proliferation, adhesion, migration and the ability of tumour cells to form colonies. Crucially, C1GalT1 suppression significantly reduced galectin-3-mediated tumour cell-cell interaction and galectin-3-promoted tumour cell activities. In the meantime, C1GalT1 suppression substantially increased MGL-mediated macrophage-tumour cell interaction and macrophage-tumour cell phagocytosis and cytokine secretion. C1GalT1-expressing cancer cells implanted in chick embryos resulted in the formation of significantly bigger tumours than C1GalT1-suppressed cells and the presence of galectin-3 increased tumour growth of C1GalT1-expressing but not C1GalT1-suppressed cells. More MGL-expressing macrophages and dendritic cells were seen to be attracted to the tumour microenvironment in ME C1galt1-/-/Erb mice than in C1galt1f/f /Erb mice. These results indicate that expression of C1GalT1 by tumour cells reciprocally controls tumour cell-cell and tumour-macrophage interactions mediated by galectin-3 and MGL with double impact on cancer development and progression. C1GalT1 overexpression in epithelial cancers therefore may represent a fundamental mechanism in cancer promotion and in reduction of immune response/surveillance in cancer progression.

Identification of two novel papillomaviruses in belugas.

Introduction: Papillomaviruses (PVs) can cause hyperplasia in the skin and mucous membranes of humans, mammals, and non-mammalian animals, and are a significant risk factor for cervical and genital cancers. Methods: Using next-generation sequencing (NGS), we identified two novel strains of papillomavirus, PV-HMU-1 and PV-HMU-2, in swabs taken from belugas (Delphinapterus leucas) at Polar Ocean Parks in Qingdao and Dalian. Results: We amplified the complete genomes of both strains and screened ten belugas and one false killer whale (Pseudorca crassidens) for the late gene (L1) to determine the infection rate. In Qingdao, 50% of the two sampled belugas were infected with PV-HMU-1, while the false killer whale was negative. In Dalian, 71% of the eight sampled belugas were infected with PV-HMU-2. In their L1 genes, PV-HMU-1 and PV-HMU-2 showed 64.99 and 68.12% amino acid identity, respectively, with other members of Papillomaviridae. Phylogenetic analysis of combinatorial amino acid sequences revealed that PV-HMU-1 and PV-HMU-2 clustered with other known dolphin PVs but formed distinct branches. PVs carried by belugas were proposed as novel species under Firstpapillomavirinae. Conclusion: The discovery of these two novel PVs enhances our understanding of the genetic diversity of papillomaviruses and their impact on the beluga population.

Diversity and independent evolutionary profiling of rodent-borne viruses in Hainan, a tropical island of China.

The risk of emerging infectious diseases (EID) is increasing globally. More than 60% of EIDs worldwide are caused by animal-borne pathogens. This study aimed to characterize the virome, analyze the phylogenetic evolution, and determine the diversity of rodent-borne viruses in Hainan Province, China. We collected 682 anal and throat samples from rodents, combined them into 28 pools according to their species and location, and processed them for next-generation sequencing and bioinformatics analysis. The diverse viral contigs closely related to mammals were assigned to 22 viral families. Molecular clues of the important rodent-borne viruses were further identified by polymerase chain reaction for phylogenetic analysis and annotation of genetic characteristics such as arenavirus, coronavirus, astrovirus, pestivirus, parvovirus, and papillomavirus. We identified pestivirus and bocavirus in Leopoldoms edwardsi from Huangjinjiaoling, and bocavirus in Rattus andamanensis from the national nature reserves of Bangxi with low amino acid identity to known pathogens are proposed as the novel species, and their rodent hosts have not been previously reported to carry these viruses. These results expand our knowledge of viral classification and host range and suggest that there are highly diverse, undiscovered viruses that have evolved independently in their unique wildlife hosts in inaccessible areas.

Alleviation of Limosilactobacillus reuteri in polycystic ovary syndrome protects against circadian dysrhythmia-induced dyslipidemia via capric acid and GALR1 signaling.

Knowledge gaps that limit the development of therapies for polycystic ovary syndrome (PCOS) concern various environmental factors that impact clinical characteristics. Circadian dysrhythmia contributes to glycometabolic and reproductive hallmarks of PCOS. Here, we illustrated the amelioration of Limosilactobacillus reuteri (L. reuteri) on biorhythm disorder-ignited dyslipidemia of PCOS via a microbiota-metabolite-liver axis. A rat model of long-term (8 weeks) darkness treatment was used to mimic circadian dysrhythmia-induced PCOS. Hepatic transcriptomics certified by in vitro experiments demonstrated that increased hepatic galanin receptor 1 (GALR1) due to darkness exposure functioned as a critical upstream factor in the phosphoinositide 3-kinase (PI3K)/protein kinase B pathway to suppress nuclear receptors subfamily 1, group D, member 1 (NR1D1) and promoted sterol regulatory element binding protein 1 (SREBP1), inducing lipid accumulation in the liver. Further investigations figured out a restructured microbiome-metabolome network following L. reuteri administration to protect darkness rats against dyslipidemia. Notably, L. reuteri intervention resulted in the decrease of Clostridium sensu stricto 1 and Ruminococcaceae UCG-010 as well as gut microbiota-derived metabolite capric acid, which could further inhibit GALR1-NR1D1-SREBP1 pathway in the liver. In addition, GALR antagonist M40 reproduced similar ameliorative effects as L. reuteri to protect against dyslipidemia. While exogenous treatment of capric acid restrained the protective effects of L. reuteri in circadian disruption-induced PCOS through inhibiting GALR1-dependent hepatic lipid metabolism. These findings purport that L. reuteri could serve for circadian disruption-associated dyslipidemia. Manipulation of L. reuteri-capric acid-GALR1 axis paves way for clinical therapeutic strategies to prevent biorhythm disorder-ignited dyslipidemia in PCOS women.

BPAT-UNet: Boundary preserving assembled transformer UNet for ultrasound thyroid nodule segmentation.

BACKGROUND AND OBJECTIVE: Accurate and efficient segmentation of thyroid nodules on ultrasound images is critical for computer-aided nodule diagnosis and treatment. For ultrasound images, Convolutional neural networks (CNNs) and Transformers, which are widely used in natural images, cannot obtain satisfactory segmentation results, because they either cannot obtain precise boundaries or segment small objects. METHODS: To address these issues, we propose a novel Boundary-preserving assembly Transformer UNet (BPAT-UNet) for ultrasound thyroid nodule segmentation. In the proposed network, a Boundary point supervision module (BPSM), which adopts two novel self-attention pooling approaches, is designed to enhance boundary features and generate ideal boundary points through a novel method. Meanwhile, an Adaptive multi-scale feature fusion module (AMFFM) is constructed to fuse features and channel information at different scales. Finally, to fully integrate the characteristics of high-frequency local and low-frequency global, the Assembled transformer module (ATM) is placed at the bottleneck of the network. The correlation between deformable features and features-among computation is characterized by introducing them into the above two modules of AMFFM and ATM. As the design goal and eventually demonstrated, BPSM and ATM promote the proposed BPAT-UNet to further constrain boundaries, whereas AMFFM assists to detect small objects. RESULTS: Compared to other classical segmentation networks, the proposed BPAT-UNet displays superior segmentation performance in visualization results and evaluation metrics. Significant improvement of segmentation accuracy was shown on the public thyroid dataset of TN3k with Dice similarity coefficient (DSC) of 81.64% and 95th percentage of the asymmetric Hausdorff distance (HD95) of 14.06, whereas those on our private dataset were with DSC of 85.63% and HD95 of 14.53, respectively. CONCLUSIONS: This paper presents a method for thyroid ultrasound image segmentation, which achieves high accuracy and meets the clinical requirements. Code is available at https://github.com/ccjcv/BPAT-UNet.

Galectin-3 promotes secretion of proteases that decrease epithelium integrity in human colon cancer cells.

Galectin-3 is a galactoside-binding protein that is commonly overexpressed in many epithelial cancers. It is increasingly recognized as a multi-functional, multi-mode promoter in cancer development, progression, and metastasis. This study reports that galectin-3 secretion by human colon cancer cells induces cancer cell secretion, in an autocrine/paracrine manner, of a number of proteases including cathepsin-B, MMP-1 and MMP-13. The secretion of these proteases causes disruption of epithelial monolayer integrity, increases its permeability and promotes tumour cell invasion. This effect of galectin-3 is shown to be mediated through induction of cellular PYK2-GSK3α/ß signalling and can be prevented by the presence of galectin-3 binding inhibitors. This study thus reveals an important mechanism in galectin-3-mediated promotion of cancer progression and metastasis. It provides further evidence to the increased realization of galectin-3 as a potential therapeutic target for the treatment of cancer.

A novel loop-mediated isothermal amplification-lateral flow dipstick method for Helicobacter pylori detection.

Introduction: To eradicate Helicobacter pylori (H. pylori) and reduce the risk of gastric cancer, a sensitive, specific, convenient, and simple detection method is needed. This study aimed to establish a novel loop-mediated isothermal amplification-lateral flow dipstick (LAMP-LFD) method for H. pylori detection. Methods: LAMP primer design software was used to design primers for the conserved sites of the H. pylori ureB gene. UreB-FIP-labeled biotin was used for LAMP amplification, and FAM-labeled probes were specifically hybridized with LAMP amplification products, which were then detected by LFD. In addition, a clinical study was conducted to assess LAMP-LFD in 20 fecal samples. Results: The results of the optimization indicated that H. pylori could be specifically detected by LFD without cross-reaction with other non-H. pylori bacteria when the LAMP was performed at 65°C for 60 min. The lower limit of the detection method was 102 copies/µL, which was 100 times the sensitivity of polymerase chain reaction (PCR). H. pylori-positive fecal samples were detected by LAMP-LFD in 13/20 patients. Discussion: In conclusion, a new LAMP-LFD assay has been fully established and confirmed for H. pylori detection. The entire process can be completed in approximately 1.5 h, with the advantages of strong specificity, high sensitivity, and simple operation. This study provides a novel potential method for the detection of H. pylori in the clinical settings of primary hospitals and low-resource countries.

African Swine Fever Virus Envelope Glycoprotein CD2v Interacts with Host CSF2RA to Regulate the JAK2-STAT3 Pathway and Inhibit Apoptosis to Facilitate Virus Replication.

African swine fever (ASF) is a highly infectious disease caused by the African swine fever virus (ASFV) in swine. It is characterized by the death of cells in infected tissues. However, the molecular mechanism of ASFV-induced cell death in porcine alveolar macrophages (PAMs) remains largely unknown. In this study, transcriptome sequencing of ASFV-infected PAMs found that ASFV activated the JAK2-STAT3 pathway in the early stages and apoptosis in the late stages of infection. Meanwhile, the JAK2-STAT3 pathway was confirmed to be essential for ASFV replication. AG490 and andrographolide (AND) inhibited the JAK2-STAT3 pathway, promoted ASFV-induced apoptosis, and exerted antiviral effects. Additionally, CD2v promoted STAT3 transcription and phosphorylation as well as translocation into the nucleus. CD2v is the main envelope glycoprotein of the ASFV, and further investigations showed that CD2v deletion downregulates the JAK2-STAT3 pathway and promotes apoptosis to inhibit ASFV replication. Furthermore, we discovered that CD2v interacts with CSF2RA, which is a hematopoietic receptor superfamily member in myeloid cells and a key receptor protein that activates receptor-associated JAK and STAT proteins. In this study, CSF2RA small interfering RNA (siRNA) downregulated the JAK2-STAT3 pathway and promoted apoptosis to inhibit ASFV replication. Taken together, ASFV replication requires the JAK2-STAT3 pathway, while CD2v interacts with CSF2RA to regulate the JAK2-STAT3 pathway and inhibit apoptosis to facilitate virus replication. These results provide a theoretical basis for the escape mechanism and pathogenesis of ASFV. IMPORTANCE African swine fever is a hemorrhagic disease caused by the African swine fever virus (ASFV), which infects pigs of different breeds and ages, with a fatality rate of up to 100%. It is one of the key diseases affecting the global livestock industry. Currently, no commercial vaccines or antiviral drugs are available. Here, we show that ASFV replicates via the JAK2-STAT3 pathway. More specifically, ASFV CD2v interacts with CSF2RA to activate the JAK2-STAT3 pathway and inhibit apoptosis, thereby maintaining the survival of infected cells and promoting viral replication. This study revealed an important implication of the JAK2-STAT3 pathway in ASFV infection and identified a novel mechanism by which CD2v has evolved to interact with CSF2RA and maintain JAK2-STAT3 pathway activation to inhibit apoptosis, thus elucidating new information regarding the signal reprogramming of host cells by ASFV.

Extracellular vesicles from iPSC-MSCs alleviate chemotherapy-induced mouse ovarian damage via the ILK-PI3K/AKT pathway.

Chemotherapy can significantly reduce follicle counts in ovarian tissues and damage ovarian stroma, causing endocrine disorder, reproductive dysfunction, and primary ovarian insufficiency (POI). Recent studies have suggested that extracellular vesicles (EVs) secreted from mesenchymal stem cells (MSCs) exert therapeutic effects in various degenerative diseases. In this study, transplantation of EVs from human induced pluripotent stem cell-derived MSCs (iPSC-MSC-EVs) resulted in significant restoration of ovarian follicle numbers, improved granulosa cell proliferation, and inhibition of apoptosis in chemotherapy-damaged granulosa cells, cultured ovaries, and in vivo ovaries in mice. Mechanistically, treatment with iPSC-MSC-EVs resulted in up-regulation of the integrin-linked kinase (ILK) -PI3K/AKT pathway, which is suppressed during chemotherapy, most likely through the transfer of regulatory microRNAs (miRNAs) targeting ILK pathway genes. This work provides a framework for the development of advanced therapeutics to ameliorate ovarian damage and POI in female chemotherapy patients.