Mutual regulation of microglia and astrocytes after Gas6 inhibits spinal cord injury.

JOURNAL/nrgr/04.03/01300535-202502000-00032/figure1/v/2024-05-28T214302Z/r/image-tiff Invasive inflammation and excessive scar formation are the main reasons for the difficulty in repairing nervous tissue after spinal cord injury. Microglia and astrocytes play key roles in the spinal cord injury micro-environment and share a close interaction. However, the mechanisms involved remain unclear. In this study, we found that after spinal cord injury, resting microglia (M0) were polarized into pro-inflammatory phenotypes (MG1 and MG3), while resting astrocytes were polarized into reactive and scar-forming phenotypes. The expression of growth arrest-specific 6 (Gas6) and its receptor Axl were significantly down-regulated in microglia and astrocytes after spinal cord injury. In vitro experiments showed that Gas6 had negative effects on the polarization of reactive astrocytes and pro-inflammatory microglia, and even inhibited the cross-regulation between them. We further demonstrated that Gas6 can inhibit the polarization of reactive astrocytes by suppressing the activation of the Yes-associated protein signaling pathway. This, in turn, inhibited the polarization of pro-inflammatory microglia by suppressing the activation of the nuclear factor-κB/p65 and Janus kinase/signal transducer and activator of transcription signaling pathways. In vivo experiments showed that Gas6 inhibited the polarization of pro-inflammatory microglia and reactive astrocytes in the injured spinal cord, thereby promoting tissue repair and motor function recovery. Overall, Gas6 may play a role in the treatment of spinal cord injury. It can inhibit the inflammatory pathway of microglia and polarization of astrocytes, attenuate the interaction between microglia and astrocytes in the inflammatory microenvironment, and thereby alleviate local inflammation and reduce scar formation in the spinal cord.

Safety and 6-month immune persistence of inactivated poliovirus vaccine (Sabin strains) simultaneously administrated with other vaccines for primary and booster immunization in Jiangxi Province, China.

OBJECTIVES: This study aims to evaluate the safety of a new inactivated poliomyelitis vaccine (Sabin strains) (sIPV) for large-scale use in primary and booster immunizations, whether simultaneously administered with other vaccines or not and to explore the persistence of all vaccines at approximately six months after vaccination. METHOD: A total of 3200 infants were recruited into this study, including 2000 infants aged 2-3 months randomly assigned (1:1) into the "sIPV basic" or the "sIPV+DTaP" group for primary immunization of sIPV. Another 1200 children aged 18 months old and above were randomly assigned (2:2:1:1) into the "sIPV booster," "sIPV+HepA-I," "sIPV+MMR", or "sIPV+HepA-L" group for booster immunization of sIPV. Adverse events within 30 days of each vaccination dose in all participants were self-reported by guardians using a WeChat mini-program. Approximately 200 blood samples were collected at 5-7 months after the final vaccination to test for antibodies against poliovirus and other viruses. RESULTS: 3198 participants in total were included in the safety study, including 1999 infants aged 2-3 months old and 1199 children aged 18-26 months old. For primary immunization, the incidence of adverse reactions in the "sIPV basic" and the "sIPV+DTaP" group were 3.19 and 6.21% (P = 0.001), respectively. For booster immunization, the incidences of adverse reaction for the "sIPV booster" group were 2.25%, while the incidence for the "sIPV +others" group in total was 2.50% (P = 0.788). Most adverse reactions were mild. Fever was the most common symptom in all groups. No vaccine-related serious adverse events (SAEs) were observed in this study. The seropositivity rates of antibodies in the "sIPV basic" and the "sIPV+DTaP" group were 92.31 and 100% against type 1 poliovirus (P = 0.031); 96.15% and 98.57% against type 2 poliovirus (P = 0.575); 98.08% and 91.43% against type 3 poliovirus (P = 0.237), respectively. Regarding booster vaccination with sIPV, whether co-administered with other vaccines or not, the seropositivity rates of antibodies against the three types of polioviruses were all 100%. Seropositivity rates of antibodies against hepatitis A, measles, mumps, and rubella were all no <77%, except for pertussis, which was <30%. CONCLUSION: sIPV demonstrated good safety and immune persistence for primary and booster vaccinations, whether administered singly or simultaneously. Antibodies against hepatitis A, measles, mumps and rubella were not disrupted by the co-vaccination. However, the seropositivity rates and geometric mean concentrations (GMCs) of antibodies against pertussis indicate the necessity for a booster dose.

Teacher support and its impact on ESL student engagement in blended learning: The mediating effects of L2 grit and intended effort.

BACKGROUND: In the shifting paradigm of English as a Foreign Language (EFL) instruction, blended learning has become increasingly prevalent, necessitating understanding factors that drive student engagement. The research delves into the intricate interaction between teacher support and student engagement, postulating that L2 grit and intended effort function as mediators within this dynamic. METHODS: We employed a cross-sectional design involving a sample of 712 EFL students engaged in blended learning courses. Through quantitative analysis, we measured the constructs of teacher support, L2 grit, intended effort, and student engagement with validated scales. Structural Equation Modeling (SEM) was applied to investigate the relationships between these variables and to test the hypothesized mediation effects. RESULTS: The results demonstrated that teacher support correlated with higher levels of student engagement. L2 grit and intended effort were identified as significant mediators in this relationship. L2 grit acted as a bridge between teacher support and student engagement, reflecting the essential role of perseverance and passion for long-term language learning objectives. Intended effort further mediated this relationship, indicating that supportive teacher behaviors foster greater student effort, enhancing overall engagement. The study also revealed a chain mediation effect, suggesting that teacher support sequentially enhances L2 grit, which in turn increases intended effort, cumulatively leading to improved student engagement. CONCLUSION: The findings offer evidence of the central role of teacher support in bolstering student engagement through the development of L2 grit and the enhancement of intended effort. This paper underlines the necessity of a supportive learning environment in blended EFL settings and presents a novel sequential mediation framework that can guide educators, curriculum designers, and policymakers in creating more effective learning experiences.

Utilizing superheated steam to prepare traditional Chinese twice-cooked pork bellies, exploring its effects on the texture and flavor of fat layers.

Fat greatly impacts the overall texture and flavor of pork belly. Twice-cooked pork bellies (TPB), typically boiled and sliced before "back to pot" being stir-fried, is a classic Sichuan cuisine among stir-fried dishes. In this study, the effects of substituting conventional pan-frying (PCV) with superheated steam (SHS) technology on the sensory, texture, microstructure and flavor of the fat layers were investigated. SHS was used as an alternative to boiling (120 °C for 15, 20, 25, and 30 min), and "back to pot" stir-frying was also by SHS. TPB precooked for 25 min (P25) with SHS performed better quality characteristics than PCV, with less collagen fiber disruption and lipid droplet area, resulting in a lower hardness and higher shear force. Besides, the low-oxygen environment of SHS retarded the lipid peroxidation, showing a significantly lower MDA content than PCV. Differently, PCV exhibited more grassy and fatty flavors, while P25 exhibited a unique aroma of fruity and creamy due to its higher UFA/SFA ratios in the pre-cooking stage. Overall, the sensory scores of P25 were comparable to those of PCV (with no significant difference), revealing that SHS is expected to be applied to the industrial production of stir-fried dishes.

TNC upregulation promotes glioma tumourigenesis through TDG-mediated active DNA demethylation.

Gliomas represent the most predominant primary malignant tumor in central nervous system. Thymine DNA glycosylase (TDG) is a central component in active DNA demethylation. However, the specific mechanisms of TDG-mediated active DNA demethylation in gliomas remain unclear. This research indicates TDG expression is overexpressed in gliomas and correlated with poor prognosis. TDG knockdown suppressed the malignant phenotype of gliomas both in vitro and vivo. Notably, RNA-seq analysis revealed a strong association between TDG and tenascin-C (TNC). ChIP-qPCR and MeDIP-qPCR assays were undertaken to confirm that TDG participates in TNC active DNA demethylation process, revealing decreased DNA methylation levels and elevated TNC expression as a result. Silencing TNC expression also suppressed the tumor malignant phenotype in both in vitro and in vivo experiments. Additionally, simultaneous silencing of TNC reduced or even reversed the glioma promotion caused by TDG overexpression. Based on our findings, we conclude that TDG exerts an indispensable role in TNC active DNA demethylation in gliomas. The DNA demethylation process leads to alternations in TNC methylation levels and promotes its expression, thereby contributing to the development of gliomas. These results suggest a novel epigenetic therapeutic strategy targeting active DNA demethylation in gliomas.

Integrating MRI-based radiomics and clinicopathological features for preoperative prognostication of early-stage cervical adenocarcinoma patients: in comparison to deep learning approach.

OBJECTIVES: The roles of magnetic resonance imaging (MRI) -based radiomics approach and deep learning approach in cervical adenocarcinoma (AC) have not been explored. Herein, we aim to develop prognosis-predictive models based on MRI-radiomics and clinical features for AC patients. METHODS: Clinical and pathological information from one hundred and ninety-seven patients with cervical AC was collected and analyzed. For each patient, 107 radiomics features were extracted from T2-weighted MRI images. Feature selection was performed using Spearman correlation and random forest (RF) algorithms, and predictive models were built using support vector machine (SVM) technique. Deep learning models were also trained with T2-weighted MRI images and clinicopathological features through Convolutional Neural Network (CNN). Kaplan-Meier curve was analyzed using significant features. In addition, information from another group of 56 AC patients was used for the independent validation. RESULTS: A total of 107 radiomics features and 6 clinicopathological features (age, FIGO stage, differentiation, invasion depth, lymphovascular space invasion (LVSI), and lymph node metastasis (LNM) were included in the analysis. When predicting the 3-year, 4-year, and 5-year DFS, the model trained solely on radiomics features achieved AUC values of 0.659 (95%CI: 0.620-0.716), 0.791 (95%CI: 0.603-0.922), and 0.853 (95%CI: 0.745-0.912), respectively. However, the combined model, incorporating both radiomics and clinicopathological features, outperformed the radiomics model with AUC values of 0.934 (95%CI: 0.885-0.981), 0.937 (95%CI: 0.867-0.995), and 0.916 (95%CI: 0.857-0.970), respectively. For deep learning models, the MRI-based models achieved an AUC of 0.857, 0.777 and 0.828 for 3-year DFS, 4-year DFS and 5-year DFS prediction, respectively. And the combined deep learning models got a improved performance, the AUCs were 0.903. 0.862 and 0.969. In the independent test set, the combined model achieved an AUC of 0.873, 0.858 and 0.914 for 3-year DFS, 4-year DFS and 5-year DFS prediction, respectively. CONCLUSIONS: We demonstrated the prognostic value of integrating MRI-based radiomics and clinicopathological features in cervical adenocarcinoma. Both radiomics and deep learning models showed improved predictive performance when combined with clinical data, emphasizing the importance of a multimodal approach in patient management.

Frailty Status, Sedentary Behaviors, and Risk of Incident Bone Fractures.

BACKGROUND: The associations of physical pre-fraily and frailty with bone fractures and the modified effect of sedentary lifestyle remain uncertain. This study was performed to explore the association of physical pre-frailty and frailty with risk of incident bone fractures; and test the modification effects of sedentary lifestyle and other risk factors. METHODS: This cohort study included 413,630 participants without bone fractures at baseline in the UK Biobank study between 2006 and 2010 and followed up to 2021. The mean age of the participants was 56.5 years. A total of 224,351 (54.2%) enrolled participants were female and 376,053 (90.9%) included participants were white. Three Cox regression models were constructed to analyze the association of pre-frailty and frailty with total fractures, hip fractures, vertebrae fractures and other fractures. RESULTS: As compared with the physical non-frailty group, the multivariate adjusted Hazard Ratios (HRs) were 1.17 (95% CI: 1.14 to 1.21) and 1.63 (95% CI: 1.53 to 1.74) for the physical pre-frailty group and frailty group, respectively (P-trend<0.001). In addition, we found that sedentary behavior time significantly accentuated the associations of physical pre-frailty and frailty with total fractures (P-interaction<0.001), hip fractures (P-interaction=0.013) and other fractures (P-interaction<0.001). CONCLUSIONS: Our results indicate that physical pre-frailty and frailty are related to higher risks of bone fractures; such association was more pronounced among those with longer sedentary behavior time.

Giant strong coupling in a Q-BICs' tetramer metasurface.

Due to their ultrahigh Q-factor and small mode volume, bound states in the continuum (BICs) are intriguing for the fundamental study of the strong coupling regime. However, the strong coupling generated by BICs in one metasurface is not always strong enough, which highly limits its efficiency in applications. In this work, we realize a giant strong coupling of at most 60 meV in a quasi-BICs' (Q-BICs) tetramer metasurface composed of four Si cylinders with two different sets of diagonal lengths. The Q-BICs are induced from two types of electric quadrupole (EQ), for which detuning can be flexibly controlled by manipulating the C4v symmetry breaking Δd. The giant Rabi splitting in our proposed metasurface performs more than 15 times of the previous works, which provides more possibilities for important nonlinear and quantum applications, such as nanolaser and quantum optics.

Clinical characteristics and surgical outcomes of vertebral lesions associated with tumor-induced osteomalacia: report of 16 patients and review of the literature.

Vertebral tumors in patients with tumor-induced osteomalacia (TIO) have a low diagnostic rate and poor postoperative outcomes. The application of 68 Ga-DOTATATE-PET/CT significantly increased the detection rate. Compared with tumor curettage, segmental resection was recommended as the preferred surgical type due to its high recovery rate. PURPOSE: Tumor-induced osteomalacia (TIO) is an acquired hypophosphatemic osteomalacia, and surgery is the first-line therapy. Most TIO tumors are found in the bones of the appendicular skeleton, cranium, and paranasal sinuses but rarely in the vertebrae. Tumor curettage and segmental resection are the two main surgical options for vertebral TIO patients. However, research on the clinical characteristics and surgical prognosis of vertebral TIO patients is rare. In the present study, for the first time, we investigated the clinical characteristics of 16 vertebral TIO patients and compared the surgical outcomes of patients who underwent surgery via two different surgical methods. METHODS: This was a retrospective cohort study. In this study, we included 16 adult TIO patients with lesions in vertebrae from Peking Union Medical College Hospital (PUMCH), all of whom underwent surgery. Baseline laboratory data were collected through medical records review. Technetium-99 m octreotide scintigraphy (99Tcm-OCT) and 68gallium-DOTA-TATE-positron emission tomography/computed tomography (68 Ga-DOTATATE-PET/CT) were conducted at the Department of Nuclear Medicine of PUMCH. The tumor histopathology was confirmed by a senior pathologist at our center. RESULTS: Vertebral TIO patients had lower serum phosphorus and TmP/GFR and higher serum alkaline phosphatase (ALP), serum parathyroid hormone (PTH), and serum C-terminal cross-linked telopeptide of type I collagen (ß-CTX) levels than the normal range. The sensitivity of 68 Ga‒DOTATATE PET/CT was 100%, significantly greater than that of 99Tcm-OCT (40%). After comparing the outcomes between the two surgical methods, we found that the recovery rate after segmental resection (62.5%) was greater than that after tumor curettage (12.5%). In the thoracic and sacral vertebrae, segmental resection surgery had a good prognosis. CONCLUSION: 68 Ga-DOTATATE PET/CT could serve as the first diagnostic tool in patients with vertebral TIO, and segmental resection could be used as the preferred surgery. This study would raise awareness of the clinical features and management of these rare vertebral TIO patients.

Catalytic Ozonation of Low Concentration Toluene over MnFeOx-USY Catalyst: Effects of Interactions between Catalytic Components and Introduction of Gas Phase NOx.

A series of Mn and Fe metal oxide catalysts loaded onto USY, as well as single metal oxides, were prepared and characterized. The effects of interactions between the catalytic components and the introduction of gas phase NO on the catalytic ozonation of toluene were investigated. Characterization showed that there existed strong interactions between MnOx, FeOx, and USY, which enhanced the content of oxygen vacancies and acid sites of the catalysts and thus boosted the generation of reactive oxygen species and the adsorption of toluene. The MnFeOx-USY catalyst with MnOx and FeOx dimetallic oxides exhibited the most excellent performance of catalytic ozonation of toluene. On the other hand, the presence of NOx in reaction gas mixtures significantly promoted both toluene conversion and mineralization, which was attributed to the formation of nitrate species on the catalysts surface and thus the increase of both acid sites and toluene oxidation sites. Meanwhile, the reaction mechanism between O3 and C7H8 was modified in which the strong interactions between MnOx, FeOx, and USY accelerated the reaction progress based on the L-H route. In addition, the formation of the surface nitrate species not only promoted reaction progress following the L-H route but also resulted in the occurrence of the reaction via the E-R route.

5G Key Technologies for Helicopter Aviation Medical Rescue.

Rapid global population growth and urbanization have heightened the demand for emergency medical rescue, with helicopter medical rescue emerging as an effective solution. The advent of 5G communication technology, characterized by large bandwidth, low latency, and high reliability, offers substantial promise in enhancing the efficiency and quality of helicopter rescue operations. However, the full integration of 5G technology into helicopter emergency medical services is still in its nascent stages and requires further development. In this viewpoint, we present our experience from the Shenzhen University General Hospital of the application of 5G low-altitude network communication technology, body area network disease sensing technology, and 5G air-ground collaborative rapid diagnosis and treatment technology in aeromedical rescue. We consider that the 5G air-to-ground collaborative rapid diagnosis and treatment technology enables high-quality remote consultation, enhancing emergency medical rescue and providing strong support for future rescue operations.

Granulosa Cell-Layer Stiffening Prevents Escape of Mural Granulosa Cells from the Post-Ovulatory Follicle.

Ovulation is vital for successful reproduction. Following ovulation, cumulus cells and oocyte are released, while mural granulosa cells (mGCs) remain sequestered within the post-ovulatory follicle to form the corpus luteum. However, the mechanism underlying the confinement of mGCs has been a longstanding mystery. Here, in vitro and in vivo evidence is provided demonstrating that the stiffening of mGC-layer serves as an evolutionarily conserved mechanism that prevents mGCs from escaping the post-ovulatory follicles. The results from spatial transcriptome analysis and experiments reveal that focal adhesion assembly, triggered by the LH (hCG)-cAMP-PKA-CREB signaling cascade, is necessary for mGC-layer stiffening. Disrupting focal adhesion assembly through RNA interference results in stiffening failure, mGC escape, and the subsequent development of an abnormal corpus luteum characterized by decreased cell density or cavities. These findings introduce a novel concept of "mGC-layer stiffening", shedding light on the mechanism that prevents mGC escape from the post-ovulatory follicle.

Natural products as inhibitors against pancreatic cancer cell proliferation and invasion: possible mechanisms.

Pancreatic cancer is one of the gastrointestinal tumors with the lowest survival rate and the worst prognosis. At the time of diagnosis, the majority of patients have missed the opportunity for radical surgical resection and opt for chemotherapy as their primary treatment choice. And drug resistance emerges during the application of the most widely used chemotherapeutic regimens such as modified FOLFIRINOX regimen, gemcitabine monotherapy or 5-Fluorouracil combination therapy, which further reduces the therapeutic efficacy. Therefore, it is urgent to explore better treatment strategies for pancreatic cancer. In recent years, more and more studies have found that natural products have significant anti-pancreatic cancer properties. In this paper, we reviewed the possible mechanisms by which natural products inhibit the proliferation and invasion of pancreatic cancer cells, including the possible mechanisms of targeting the inhibition of the growth and proliferation regulatory pathways of pancreatic cancer cells, inducing apoptosis and autophagy of pancreatic cancer cells, inhibiting the EMT process of pancreatic cancer cells, and inhibiting the angiogenesis of pancreatic cancer. Meanwhile, natural products have also hindered the progress of their basic and clinical research due to the complexity of their composition and the limitation of biological extraction technology. Further exploration of the specific molecular mechanisms of natural products to inhibit the proliferation and invasion of pancreatic cancer cells, optimization of purification and preparation techniques, and enrichment of basic and clinical trials to verify their efficacy and safety may be the future direction of natural products in the field of anti-pancreatic cancer research.

Evaluating anemia in HIV-infected patients using chest CT.

Objective: The aim of this study was to investigate the role of the Hounsfield unit value of chest CT non-contrast enhanced scan in evaluating the severity of anemia in HIV-infected patients. Methods: Patients with HIV infection combined with anemia admitted to the Kunming Third People's Hospital were retrospectively collected and divided into mild anemia, moderate anemia, and severe anemia groups by peripheral hemoglobin (HB) content and calculated the ratio of ventricular septum density (VSD) to left ventricular density (LVD) and VSD to right ventricular density (RVD); then, the above patients were divided into the critical value group and the non-critical value group according to HB and compared the differences of LVD, RVD, VSD/LVD, and VSD/RVD in the two groups of patients. Results: A total of 126 patients were included, with a mean age of 47.9 ± 11.1 years; 43 cases were in the mild anemia group, 59 cases were in the moderate anemia group, and 24 cases were in the severe anemia group; the differences in LVD, RVD, VSD/LVD, and VSD/RVD were significant in the three groups; VSD/LVD was an independent predictor for the diagnosis of anemia critical value in the non-critical value group vs critical value group by multifactorial binary logistic regression analysis, and the ROC was plotted using VSD/LVD with an area under the curve of 0.731. Conclusions: The measurement of cardiac cavity density and ventricular septal density under CT plain film scan has a high accuracy in evaluating the severity of anemia in patients with HIV infection and can quickly determine the severity of HIV infection in the early stage and treat it as soon as possible.

Switching the Chemoselectivity in the Preparation of [18F]FNA-N-CooP, a Free Thiol-Containing Peptide for Targeted Positron Emission Tomography Imaging of Fatty Acid Binding Protein 3.

Fatty acid binding protein 3 (FABP3) is expressed both in tumor cells and in the tumor vasculature, making it a potential target for medical imaging and therapy. In this study, we aimed to radiolabel a CooP peptide with a free amino and thiol group, and evaluate the radiolabeled product [18F]FNA-N-CooP for imaging FABP3 expression in breast cancer brain metastases by positron emission tomography. [18F]FNA-N-CooP was prepared by highly chemoselective N-acylation and characterized using different chemical approaches. We validated its binding to the target using in vitro tissue section autoradiography and performed stability tests in vitro and in vivo. [18F]FNA-N-CooP was successfully synthesized in 16.8% decay-corrected radiochemical yield with high radiochemical purity (98.5%). It exhibited heterogeneous binding on brain metastasis tissue sections from a patient with breast cancer, with foci of radioactivity binding corresponding to FABP3 positivity. Furthermore, the tracer binding was reduced by 55% in the presence of nonradioactive FNA-N-CooP a blocker, indicating specific tracer binding and that FABP3 is a viable target for [18F]FNA-N-CooP. Favorably, the tracer did not bind to necrotic tumor tissue. However, [18F]FNA-N-CooP displayed limited stability both in vitro in mouse plasma or human serum and in vivo in mouse, therefore further studies are needed to improve the stability [18F]FNA-N-CooP to be used for in vivo applications.

Identification of Transcription Factors of Santalene Synthase Gene Promoters and SaSSY Cis-Elements through Yeast One-Hybrid Screening in Santalum album L.

The main components of sandalwood heartwood essential oil are terpenoids, approximately 80% of which are α-santalol and ß-santalol. In the synthesis of the main secondary metabolites of sandalwood heartwood, the key gene, santalene synthase (SaSSY), can produce α-santalene and ß-santalene by catalyzed (E, E)-FPP. Furthermore, santalene is catalyzed by the cytochrome monooxygenase SaCYP736A167 to form sandalwood essential oil, which then produces a fragrance. However, the upstream regulatory mechanism of the key gene santalene synthase remains unclear. In this study, SaSSY (Sal3G10690) promoter transcription factors and SaSSY cis-elements were screened. The results showed that the titer of the sandalwood cDNA library was 1.75 × 107 CFU/mL, 80% of the inserted fragments identified by PCR were over 750 bp in length, and the positivity rate of the library was greater than 90%. The promoter region of the SaSSY gene was shown to have the structural basis for potential regulatory factor binding. After sequencing and bioinformatics analysis, we successfully obtained 51 positive clones and identified four potential SaSSY transcriptional regulators. Sal6G03620 was annotated as the transcription factor MYB36-like, and Sal8G07920 was annotated as the small heat shock protein HSP20 in sandalwood. Sal1G00910 was annotated as a hypothetical protein of sandalwood. Sal4G10880 was annotated as a homeobox-leucine zipper protein (ATHB-15) in sandalwood. In this study, a cDNA library of sandalwood was successfully constructed using a yeast one-hybrid technique, and the transcription factors that might interact with SaSSY gene promoters were screened. This study provides a foundation for exploring the molecular regulatory mechanism involved in the formation of sandalwood heartwood.

Research Progress of Pyroptosis in Diabetic Kidney Disease.

Pyroptosis, known as one typical mode of programmed cell death, is generally characterized by the cleaved gasdermin family (GSDMs) forming pores in the cell membrane and inducing cell rupture, and the activation of aspartate-specific proteases (caspases) has also been found during this process. Diabetic Kidney Disease (DKD) is caused by the complication of diabetes in the kidney, and the most important kidney's function, Glomerular Filtration Rate (GFR), happens to drop to less than 90% of its usual and even lead to kidney failure in severe cases. The persistent inflammatory state induced by high blood glucose implies the key pathology of DKD, and growing evidence shows that pyroptosis serves as a significant contributor to this chronic immune-mediated inflammatory disorder. Currently, the expanded discovery of GSDMs, pyroptosis, and its association with innate immunity has been more attractive, and overwhelming research is needed to sort out the implication of pyroptosis in DKD pathology. In this review, we comb both classical studies and newly founds on pyroptosis, prick off the novel awakening of pyroptosis in DKD, and center on the significance of pyroptosis in DKD treatment, aiming to provide new research targets and treatment strategies on DKD.

The regulatory role of m6A modification in the maintenance and differentiation of embryonic stem cells.

As the most prevalent and reversible internal epigenetic modification in eukaryotic mRNAs, N 6-methyladenosine (m6A) post-transcriptionally regulates the processing and metabolism of mRNAs involved in diverse biological processes. m6A modification is regulated by m6A writers, erasers, and readers. Emerging evidence suggests that m6A modification plays essential roles in modulating the cell-fate transition of embryonic stem cells. Mechanistic investigation of embryonic stem cell maintenance and differentiation is critical for understanding early embryonic development, which is also the premise for the application of embryonic stem cells in regenerative medicine. This review highlights the current knowledge of m6A modification and its essential regulatory contribution to the cell fate transition of mouse and human embryonic stem cells.

Diagnostic and prognostic role of LINC01767 in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a primary contributor to cancer-related mortality on a global scale. However, the underlying molecular mechanisms are still poorly understood. Long noncoding RNAs are emerging markers for HCC diagnosis, prognosis, and therapeutic target. No study of LINC01767 in HCC was published. AIM: To conduct a multi-omics analysis to explore the roles of LINC01767 in HCC for the first time. METHODS: DESeq2 Package was used to analyze different gene expressions. Receiver operating characteristic curves assessed the diagnostic performance. Kaplan-Meier univariate and Cox multivariate analyses were used to perform survival analysis. The least absolute shrinkage and selection operator (LASSO)-Cox was used to identify the prediction model. Subsequent to the validation of LINC01767 expression in HCC fresh frozen tissues through quantitative real time polymerase chain reaction, next generation sequencing was performed following LINC01767 over expression (GSE243371), and Gene Ontology/Kyoto Encyclopedia of Genes and Genomes/Gene Set Enrichment Analysis/ingenuity pathway analysis was carried out. In vitro experiment in Huh7 cell was carried out. RESULTS: LINC01767 was down-regulated in HCC with a log fold change = 1.575 and was positively correlated with the cancer stemness. LINC01767 was a good diagnostic marker with area under the curve (AUC) [0.801, 95% confidence interval (CI): 0.751-0.852, P = 0.0106] and an independent predictor for overall survival (OS) with hazard ratio = 1.899 (95%CI: 1.01-3.58, P = 0.048). LINC01767 nomogram model showed a satisfied performance. The top-ranked regulatory network analysis of LINC01767 showed the regulation of genes participating various pathways. LASSO regression identified the 9-genes model showing a more satisfied performance than 5-genes model to predict the OS with AUC > 0.75. LINC01767 was down-expressed obviously in tumor than para-tumor tissues in our cohort as well as in cancer cell line; the over expression of LINC01767 inhibit cell proliferation and clone formation of Huh7 in vitro. CONCLUSION: LINC01767 was an important tumor suppressor gene in HCC with good diagnostic and prognostic performance.