Expression profile of microRNAs in bovine lymphocytes infected with Theileria annulata and treated with buparvaquone.

Several miRNA-based studies on Theileria-transformed bovine cells have been conducted; however, the mechanism by which transformed cells exhibit uncontrolled proliferation is not yet fully understood. Therefore, it is necessary to screen more microRNAs that may play a role in the transformation process of host cells infected with Theileria annulata to better understand the transformation mechanisms of Theileria-infected cells. RNA sequencing was used to analyze miRNAs expression in the host bovine lymphocytes infected with T. annulata at different time points after buparvaquone (BW720) treatment and DMSO treatment (control groups). Differential miRNAs related to cell proliferation and apoptosis were identified through comparison with gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, and a regulatory network of miRNA-mRNA was constructed. In total, 272 differentially expressed miRNAs were found at 36, 60 and 72 h. The miRNAs change of bta-miR-2285t, novel-miR-622, bta-miR-2478, and novel-miR-584 were significant. Analysis of 27 of these co-differential expressed miRNAs revealed that 15 miRNAs were down-regulated and 12 miRNAs were up-regulated. A further analysis of the changes in the expression of each of these 27 miRNAs in the three datasets suggested that bta-miR-2285t, bta-miR-345-5p, bta-miR-34a, bta-miR-150, and the novel-miR-1372 had significantly changed. Predicted target genes for these 27 miRNAs were analyzed by KEGG and the results demonstrated that EZR, RASSF, SOCS1 were mainly enriched in the signaling pathway microRNAs in cancer. MAPKAPK2, RELB, FLT3LG, and GADD45B were mainly enriched in the MAPK signaling pathway, and some genes were enriched in Axon guidance. This study has provided valuable information to further the understanding of the regulatory function of miRNAs in the host microenvironment and host-parasite interaction mechanisms.

The apparent diffusion coefficient based on small-field DWI is superior to T2-weighted imaging in evaluating neurological dysfunction of degenerative cervical myelopathy.

PURPOSE: To investigate the clinical application of zonally magnified oblique multislice (ZOOM) imaging technology in patients with degenerative cervical myelopathy (DCM) and compare it with T2WI imaging. METHODS: A total of 111 patients diagnosed with DCM were recruited. According to mJOA, patients with DCM were divided into ND + group with neurological dysfunction and ND- group without neurological dysfunction. Routine MRI and ZOOM-DWI were performed on 3.0 T MRI to obtain sagittal T2WI and apparent diffusion coefficient (ADC) diagram. ADC values of the narrow segment and its adjacent upper and lower segments were measured, and compared between the ND + and ND- groups. The correlation between ADC value of cervical spinal cord and mJOA score was analyzed. Additionally, ROC curves were plotted to calculate the AUC values. RESULTS: The comparison between ND + and ND- groups shows that there are significant differences in mJOA score, T2WI, anteroposterior diameter of spinal canal, ADC values of narrow, upper and lower segment (P < 0.05). In ND + group, there is a significant difference between ADC values of the narrow and its upper and lower segments (P < 0.001), while with no significant difference in ADC values of the upper and lower segments (P > 0.05). Results of correlation analysis indicate that in the ND + group, neurological dysfunction evaluated by mJOA scores is correlated with increased ADC values of the narrow segment (r = -0.52, P < 0.001), but not significantly correlated with ADC values of the upper and lower segments. Furthermore, T2WI, anteroposterior diameter of the spinal canal, and cervical cord ADC values all has diagnostic efficacy in evaluating neurological dysfunction in DCM (AUC > 0.5, P < 0.05), with the ADC value of the narrow segment being optimal. CONCLUSION: The ADC value of spinal cord obtained by small-field ZOOM-DWI can be used to evaluate neurological dysfunction in DCM, and is superior to traditional T2WI.

HA-TiNet: Learning a Distinctive and General 3D Local Descriptor for Point Cloud Registration.

Extracting geometric features from 3D point clouds is widely applied in many tasks, including registration and recognition. We propose a simple yet effective method, termed height-azimuth image based transformation-invariant net (HA-TiNet), to learn a distinctive, general and rotation-invariant 3D local descriptor. HA-TiNet is composed of a height-azimuth image generator and a feature extraction net. Based on a local reference axis (LRA), the height-azimuth image generator first partitions local region along the plane-radial direction, and then implements a statistic of height and azimuth information in each divided space to generate a set of height-azimuth images. The generated height-azimuth images are invariant in the rotation around x- and y-axes and have high accuracy due to the high repeatability of an LRA. Besides, they can be easily embedded in 2D convolutional neural networks (CNNs). Our feature extraction net learns the information on the height-azimuth images using a ResNet-based backbone and a rotation-invariant layer. The ResNet-based backbone is lightweight while very effective. The rotation-invariant layer removes the rotation-variance around z-axis, making our descriptor have full rotation-invariance. Extensive experiments on indoor and outdoor datasets show that our method presents superior overall performance, and exhibits strong descriptiveness and generalization ability compared to the state-of-the-art descriptors. The source code will be made publicly available at https://github.com/ahulq/HA-TiNet.

Two "turn on" fluorescence probes based on nitroso recognition group for detecting hydrogen sulfide.

Hydrogen sulfide is a vital signaling molecule which holds a pivotal position in numerous biological functions. In this research, two novel "OFF-ON" fluorescence probes named YNO and TNO were designed based on the nitroso recognition group to detect H2S. Both YNO and TNO performed outstanding response rate and linear relationship between the fluorescence intensity and the concentration of H2S. YNO possessed larger Stokes shift and longer emission wavelength. TNO had lower limit of detection. In addition, YNO was successful applied to sense endogenous and exogenous H2S and target endoplasmic reticulum (ER) in Hela cells.

Haemonchus contortus alters distribution and utilization of protein and amino acids in different tissues of host sheep.

The objective was to determine host animal protein/amino acid redistribution and use among the abomasum, duodenum and muscle of sheep infected with Haemonchus contortus. Sixteen male Ujumqin sheep (32.4 ± 3.9 kg) were dewormed and randomly assigned to two groups, infected or not infected with H. contortus (GIN and CON). The GIN group had lower (P < 0.05) dry matter intake, average daily gain, and live body weight than CON, with extensive focal infiltration of lymphocytes in the lamina propria and bottom of the abomasal epithelium. In the abomasum and duodenum, there were 100 and 220 genes, respectively, that were up-regulated, whereas 56 and 149 were down-regulated. In the abomasum, the most enriched KEGG pathways were related to immunity and inflammation reaction, including: viral protein interaction with cytokine and cytokine receptor (P = 0.017), influenza A (P = 0.030), IL-17 signaling pathway (P = 0.030). In the duodenum, KEGG pathways were more enriched in nutrient metabolism, including pancreatic secretion (P < 0.001), protein digestion and absorption (P < 0.001), graft-versus-host disease (P = 0.004). Furthermore, most genes related with the above KEGG pathways were increased in the abomasum but decreased in the duodenum. Amino acid profiles in abomasum and duodenum of CON and GIN groups were clustered in a partial least-squares discriminant analysis model, with significant changes in 36 and 19 metabolites in abomasal and duodenal chyme, respectively. Further confirmed by transcriptome-targeted metabolome association analysis, GIN mainly enhanced metabolism of arginine and sulphur amino acids in abomasum and those metabolic pathways were associated. Meanwhile, GIN mainly decreased pyruvate related amino acid metabolism in duodenum. Moreover, concentrations of Arg (P = 0.036), His (P = 0.027), and Cys (P = 0.046) in longissimus thoracis et lumborum were decreased in GIN, whereas concentrations of Gly (P = 0.012) and Ala (P = 0.046) were increased. In conclusion, H. contortus enhanced metabolism of arginine and sulphur amino acids in the abomasum; decreased pyruvate metabolism in the duodenum; and drove more protein/amino acids for abomasal tissues to resist physical and immune damage, reducing protein and amino acids in duodenum and muscle for support host growth. Specific nutrients (such like arginine, histidine, and cysteine) may play important role in control gastrointestinal nematode infection for ruminant.

Elastic wave control in reticulated plates using Schwarz primitive cells.

In this work, the Schwarz primitive unit cell is used as the building block of different types of metastructures for steering and focusing elastic vibrations. The emergence of a Bragg-type bandgap when constructing a two-dimensional plate from such unit cells is experimentally validated. It is demonstrated that increasing both mass and porosity of the Schwarz primitive leads to a decrease in the frequency of the out-of-plane propagating wave targeted in this study. By arranging these modified Schwarz primitive unit cells in constant and graded layouts, two-dimensional plates with an embedded metabarrier and a metalens are numerically designed. The metabarrier protects an interior area of the plate from the propagating waves on a wide frequency band (approx. 1.4-3.4 kHz). Equally, the refractive index profile necessary for gradient index lenses is obtained via a progressive variation of the added mass or, alternatively, the porosity of the unit cell over a rectangular area. For the first time, bending of the out-of-plane mode towards the focusing point is practically validated in a challenging mesoscale experiment requiring the assembly of different three-dimensional printed sections of the plate. The increased porosity design is advantageous not only in terms of overall lightweight, but also towards additive manufacturing as it requires less material.This article is part of the theme issue 'Current developments in elastic and acoustic metamaterials science (Part 1)'.

Novel fluorescence probe for ClO- in living cells: Based on FRET mechanism.

Hypochlorous acid (HClO) as a kind of reactive oxygen species (ROS) plays a vital role in many biological processes. Organic fluorescence probes have attracted great interests for the detection of HClO, due to their relatively high selectivity and sensitivity, satisfactory spatiotemporal resolution and good biocompatibility. Constructing fluorescence probes to detect HClO with advantages of large Stokes shift, wide emission gap, near infrared emission and good water solubility is still challenging. In this work, a new ratiometric fluorescence probe (named HCY) for HClO was developed. FRET-based HCY was constructed by bonding a coumarin and a flavone fluorophore. In absence of HClO, HCY exists FRET process, however, FRET is inhibited in the presence of HClO because the conjugated double bond broke. Due to the good match of the emission spectrum of the donor and the absorption spectrum of the acceptor, the FRET system appears favorable energy transfer efficiency. HCY showed high sensitivity and rapid response time. The linearity between the ratios of fluorescence intensity and concentration of HClO was established with a low limit of detection. What's more, HCY was also applied for fluorescence images of HClO in RAW264.7 cells.

Periodontal disease increases the severity of chronic obstructive pulmonary disease: a Mendelian randomization study.

BACKGROUND: Recent research suggests that periodontitis can increase the risk of chronic obstructive pulmonary disease (COPD). In this study, we performed two-sample Mendelian randomization (MR) and investigated the causal effect of periodontitis (PD) on the genetic prediction of COPD. The study aimed to estimate how exposures affected outcomes. METHODS: Published data from the Gene-Lifestyle Interaction in the Dental Endpoints (GLIDE) Consortium's genome-wide association studies (GWAS) for periodontitis (17,353 cases and 28,210 controls) and COPD (16,488 cases and 169,688 controls) from European ancestry were utilized. This study employed a two-sample MR analysis approach and applied several complementary methods, including weighted median, inverse variance weighted (IVW), and MR-Egger regression. Multivariable Mendelian randomization (MVMR) analysis was further conducted to mitigate the influence of smoking on COPD. RESULTS: We chose five single-nucleotide polymorphisms (SNPs) as instrumental variables for periodontitis. A strong genetically predicted causal link between periodontitis and COPD, that is, periodontitis as an independent risk factor for COPD was detected. PD (OR = 1.102951, 95% CI: 1.005-1.211, p = 0.039) MR-Egger regression and weighted median analysis results were coincident with those of the IVW method. According to the sensitivity analysis, horizontal pleiotropy's effect on causal estimations seemed unlikely. However, reverse MR analysis revealed no significant genetic causal association between COPD and periodontitis. IVW (OR = 1.048 > 1, 95%CI: 0.973-1.128, p = 0.2082) MR Egger (OR = 0.826, 95%CI:0.658-1.037, p = 0.1104) and weighted median (OR = 1.043, 95%CI: 0.941-1.156, p = 0.4239). The results of multivariable Mendelian randomization (MVMR) analysis, after adjusting for the confounding effect of smoking, suggest a potential causal relationship between periodontitis and COPD (P = 0.035). CONCLUSION: In this study, periodontitis was found to be independent of COPD and a significant risk factor, providing new insights into periodontitis-mediated mechanisms underlying COPD development.

Research progress of immunotherapy for advanced head and neck cancer.

Head and neck cancer accounts for about one-fifth of all malignant tumors, and the incidence is increasing year by year. The overall mortality rate was high and the 5-year survival rate was low. At present, the combination of surgery, radiotherapy, and chemotherapy is the main treatment in clinical practice, but the treatment of recurrent or metastatic advanced head and neck cancer is still a challenge. With the rise of immunotherapy, more and more studies on immune checkpoint inhibitors have been conducted. This review summarizes the mechanism, clinical application and safety of immunotherapy for advanced head and neck cancer.

New alkaloids from Stemona tuberosa and structural revision of tuberostemonols P and R.

Three Stemona alkaloids named stemotuberines A-C (1-3) with unique C17N frameworks, presumably formed by elimination of the C-11-C-15 lactone ring of the stichoneurine skeleton, were isolated from the roots of Stemona tuberosa. Their structures were elucidated by spectroscopic analysis, X-ray diffraction, and computational methods. Compounds 2 and 3 showed inhibition (IC50 values of 37.1 and 23.2 µM, respectively) against LPS-induced nitric oxide production in RAW 264.7 cells. In addition, concern was expressed about the reported plant origin (S. sessilifolia) of the recently described alkaloids tuberostemonols O-R (4-7), which should be S. tuberosa. NMR calculations indicated structural misassignment of these compounds except for 6. Isolation of tuberostemonol P (5) from our material of S. tuberosa allowed for a close examination of the spectroscopic data leading to the revised structure 5a. Tuberostemonol R (7) was found to have identical 1H and 13C NMR data to the well-known alkaloid croomine, and therefore its structure including relative stereochemistry must be revised as 7a.

A near-infrared fluorescent probe for simultaneous detection of pH and viscosity.

In this work, we developed a ratiometric fluorescent probe (NT) based on ICT framework in near-infrared (NIR) which could detect pH and viscosity simultaneously. Long emission wavelength in NIR could protect the probe from interference of background fluorescence and improve the accuracy of the test. Due to the presence of thiazole-salt, the probe possessed good water solubility and could respond immediately to pH in water system. The pH values measured by NT in the actual samples were not much different from that measured by the pH meter, therefore, NT could give excellent accuracy. NT realized the reversible detection of pH by protonation and deprotonation. NT was used successfully to detect the pH of actual water samples, human serum and meat, as well as the viscosity variation caused by thickeners. Additionally, NT could monitor the changes of pH and viscosity in living cells. Therefore, the novel probe exhibited potential application in the fields of the environment, human health and food safety evaluation.

[Review of clinical effects of disk-up sinus reamer(DSR)-based internal sinus floor elevation with implantation in 10 years].

PURPOSE: To analyze the bone remodeling around the implant 10 years after disk-up sinus reamer(DSR)-based internal sinus floor elevation with implantation and to investigate the influence of different factors on implant retention. METHODS: The clinical and imaging data of patients undergoing DSR-based sinus floor elevation with simultaneous implantation were collected from the Department of Dental Implantology, Affiliated Hospital of Qingdao University from January 2008 to December 2011. Panoramic film and CBCT were used to measure the changes of bone mass around implant in different periods. Kaplan-Meier and Log-rank tests were used to analyze the effects of different factors on implant retention with SPSS 26.0 software package. RESULTS: The study included 98 patients with a total of 128 implants. During the follow-up of 0-168 months, 7 implants failed, and the remaining formed good osseointegration and functioned, with a 10-year cumulative retention rate of 94.53%. The height of bone formation was (0.29±0.15) mm at the top and (2.74±0.66) mm in the sinus of 75 implant sites with complete imaging data obtained ten years after surgery. Kaplan-Meier and Log-rank tests showed that 8 factors including initial bone height, elevated bone height, mucosal perforation, implant length, implant torsion, diabetes, smoking and periodontitis had significant effects on implant retention. CONCLUSIONS: The DSR-based internal sinus floor elevation with implantation is a reliable and stable bone augmentation operation for vertical bone defect in maxillary posterior region, with a 10-year cumulative retention rate of no less than 94%. Initial bone height, elevated bone height, mucosal perforation, implant length, implant torsion, diabetes, smoking and periodontitis are the important factors affecting the long-term retention rate of implants.

A highly sensitive ratiometric fluorescent probe for detecting HSO3-/SO32- and viscosity change based on FRET/TICT mechanism.

BACKGROUND: Sulfur dioxide (SO2) is a significant gas signaling molecule in organisms, and viscosity is a crucial parameter of the cellular microenvironment. They are both involved in regulating many physiological processes in the human body. However, abnormalities in SO2 and viscosity levels are associated with various diseases, such as cardiovascular disease, lung cancer, respiratory diseases, neurological disorders, diabetes and Alzheimer's disease. Hence, it is essential to explore novel and efficient fluorescent probes for simultaneously monitoring SO2 and viscosity in organisms. RESULTS: We selected quinolinium salt with good stability, high fluorescence intensity, good solubility and low cytotoxicity as the fluorophore and developed a highly sensitive ratiometric probe QQD to identify SO2 and viscosity changes based on Förster resonance energy transfer/twisted intramolecular charge transfer (FRET/TICT) mechanism. Excitingly, compared with other probes for SO2 detection, QQD not only identified HSO3-/SO32- with a large Stokes shift (218 nm), low detection limit (1.87 µM), good selectivity, high energy transfer efficiency (92 %) and wide recognition range (1.87-200 µM), but also identified viscosity with a 26-fold fluorescence enhancement and good linearity. Crucially, QQD was applied to detect HSO3-/SO32- and viscosity in actual water and food samples. In addition, QQD had low toxicity and good photostability for imaging HSO3-/SO32- and viscosity in cells. These results confirmed the feasibility and reliability of QQD for HSO3-/SO32- and viscosity imaging and environmental detection. SIGNIFICANCE: We reported a unique ratiometric probe QQD for detecting HSO3-/SO32- and viscosity based on the quinolinium skeleton. In addition to detecting HSO3-/SO32- and viscosity change in actual water and food samples, QQD could also monitor the variations of HSO3-/SO32- and viscosity in cells, which provided an experimental basis for further exploration of the role of SO2 derivatives and viscosity in biological systems.

Acid Promoted Tetrafunctionalization of Terminal Alkynes: Geminal Diazidation and Dibromination.

The synthesis of complex alkanes by the tetrafunctionalization of alkynes is limited and challenging. Herein, an unprecedented efficient geminal diazidation and dibromination of terminal alkynes is developed, which provides novel access to structurally diverse organic azides. The approach has exclusive chemo- and regioselectivity and features mild reaction conditions, good tolerance of various functional groups, and more crucially, no metal involved in the reaction, thereby benefiting the late-stage decoration of medicinal molecules. A mechanistic study showed that the current geminal diazidation and dibromination proceeds via a radical pathway.

Palladium-Catalyzed Intermolecular Dehydrogenative C-2 Pentenylation of Indoles with 2-Methyl-2-butene.

Five-carbon (C5) units are the fundamental building blocks that constitute a multitude of natural products. Herein we report an unprecedented unusual C5 functionalization of indole regioselectively at the C-2-position enabled by a (2-pyridyl)sulfonyl-directing palladium-catalyzed dehydrogenative strategy with a bulk chemical 2-methyl-2-butene as a C5 source. Compared to typical C5 functionalization using pentenyl alcohols, carbonates, borates, or halides as the C5 source, the protocol not only has a low cost advantage but also is of atom and step economy.

Polystyrene exposure induces lamb gastrointestinal injury, digestive disorders and inflammation, decreasing daily gain, and meat quality.

Microplastics (MPs), recognized as an emerging environmental menace, have been extensively investigated in both marine and terrestrial fauna. This study is comprehensive to investigate how polystyrene (PS) affects ruminant animals. The experimental design comprised 24 individually housed lambs, divided into a CON group (diet without PS) and three PS-exposed (25 µm, 50 µm, 100 µm) groups, each with six lambs, the exposure of PS was 100 mg/day, and the duration of exposure was 60 days. The study yielded noteworthy results: (ⅰ) PS leads to a decrease in average daily gain along with an increase in feed conversion rate. (ⅱ) PS decreases rumen ammonia nitrogen. The rumen microbiota diversity remains consistent. However, the relative abundance of Bacteroidetes and Actinobacteria increased in the PS-exposed groups, while the relative abundance of Coriobacteriales_incertae_Sedis and Prevotellaceae_YAB2003_group decreased. (ⅲ) PS leads to decrease in hemoglobin, thrombocytocrit, and albumin levels in lamb blood, thus triggering oxidative stress accumulation, along with swelling of the kidneys and liver. (ⅳ) PS inflicts severe damage to jejunum, consequently impacting digestion and absorption. (ⅴ) PS reduces meat quality and the nutritional value. In conclusion, PS-exposure inhibited lambs' digestive function, adversely affects blood and organs' health status, reducing average daily gain and negatively influencing meat quality. PS particles of 50-100 µm bring worse damage to lambs. This research aims to fill the knowledge void concerning MPs' influences on ruminant animals, with a specific focus on the meat quality of fattening lambs.

A near-infrared fluorescent probe based FRET for ratiometric sensing of H2O2 and viscosity in live cells.

Hydrogen peroxide (H2O2) and viscosity play vital roles in the cellular environment as signaling molecule and microenvironment parameter, respectively, and are associated with many physiological and pathological processes in biological systems. We developed a near-infrared fluorescent probe, CQ, which performed colorimetric and ratiometric detection of H2O2 and viscosity based on the FRET mechanism, and was capable of monitoring changes in viscosity and H2O2 levels simultaneously through two different channels. Based on the specific reaction of H2O2 with borate ester, CQ exhibited a significant ratiometric response to H2O2 with a large Stokes shift of 221 nm, a detection limit of 0.87 µM, a near-infrared emission wavelength of 671 nm, a response time of 1 h, a wide detection ranges of 0.87-800 µM and a high energy transfer efficiency of 99.9 %. CQ could also recognize viscosity by the TICT mechanism, and efficiently detect viscosity changes caused by food thickeners. More importantly, CQ could successfully detect endogenous/exogenous H2O2 and viscosity in live HeLa cells, which was expected to be a practical tool for detecting H2O2 and viscosity in live cells.

Non-cytopathic bovine viral diarrhea virus (BVDV) inhibits innate immune responses via induction of mitophagy.

Bovine viral diarrhea virus (BVDV) belongs to the genus Pestivirus within the family Flaviviridae. Mitophagy plays important roles in virus-host interactions. Here, we provide evidence that non-cytopathic (NCP) BVDV shifts the balance of mitochondrial dynamics toward fission and induces mitophagy to inhibit innate immune responses. Mechanistically, NCP BVDV triggers the translocation of dynamin-related protein (Drp1) to mitochondria and stimulates its phosphorylation at Ser616, leading to mitochondrial fission. In parallel, NCP BVDV-induced complete mitophagy via Parkin-dependent pathway contributes to eliminating damaged mitochondria to inhibit MAVS- and mtDNA-cGAS-mediated innate immunity responses, mtROS-mediated inflammatory responses and apoptosis initiation. Importantly, we demonstrate that the LIR motif of ERNS is essential for mitophagy induction. In conclusion, this study is the first to show that NCP BVDV-induced mitophagy plays a central role in promoting cell survival and inhibiting innate immune responses in vitro.

GDF10 and IDO1 as a thyroid cancer prognostic biomarker associated with immune infiltration.

Objection: The aim of this work is to screen the immune-related genes to predict the prognosis and provide a new direction of treatment for patients with thyroid cancer (THCA). Methods: The mRNA and clinical features of THCA patients were collected from the Cancer Genome Atlas (TCGA) databases. The immune-related genes were obtained from the ImmPort databases. The bio-information methods were performed to screen the differential expression genes (DEGs) and genes related to immunity between the THCA patients and normal individuals. On this basis, the hub prognosis immunity genes were screened by Veen. The related genes were obtained by constructing the protein-protein interaction network. The enrichment analyses were performed based on the protein and protein interaction (PPI) related genes. The hub immune checkpoint was screened by correlation analysis. Finally, the hub gene and the immunity checkpoint-miRNA (or transcription factor, drug) interaction network were constructed. A drug-sensitive analysis also was performed. Results: The GDF10 was screened. The PPI genes were enriched in the TGF-beta signaling pathway, signaling pathways regulating, the pluripotency of stem cells, Cytokine-cytokine receptor interaction, and so on. The hub immunity checkpoint IDO1 was obtained. The joint indicator of two hub genes was positively related to the thyroid differentiation score. Three interaction factors were found to be related to the two hub genes, and 7 kinds of drugs screened act on the two hub genes at the same time. Conclusion: This work indicated that immune-related gene GDF10 and immune checkpoint IDO1 are important for the prognosis prediction of THCA patients, and immunity is involved in the proliferation, and differentiation of tumor cells.

Dapagliflozin prevents kidney podocytes pyroptosis via miR-155-5p/HO-1/NLRP3 axis modulation.

Diabetic nephropathy (DN) is a significant clinical microvascular complication associated with diabetes mellitus (DM), and end-stage diabetes giving rise to kidney failure is developing into the major etiological factor of chronic kidney failure. Dapagliflozin is reported to limit podocyte damage in DM, which has proven to protect against renal failure. Mounting evidence has demonstrated that pyroptosis is associated with DM progression. Nevertheless, whether pyroptosis causes DN and the underlying molecular pathways remain obscure. In this study, we aimed to explore the antipyroptotic attributes of dapagliflozin and elucidate the underlying mechanisms of kidney damage in diabetes. In vivo, experiments were conducted in streptozotocin (STZ)-induced type 2 diabetic mice, which were administered dapagliflozin via gavage for 6 weeks. Subsequently, the specific organizational characteristics and expression of pyroptosis-related genes were evaluated. Intragastric dapagliflozin administration markedly reduced renal tissue injury. Meanwhile, dapagliflozin also attenuated the expression level of pyroptosis associated genes, including ASC, cleaved Caspase-1, GSDMD N-termini, NLRP3, IL-18, and IL-1ß in renal tissue of dapagliflozin-treated animals. Similar antipyroptotic effects were observed in palmitic acid (PA)-treated mouse podocytes. We also found that heme oxygenase 1 (HO-1) enhanced the protection of mouse podocyte clone 5 cells (MPC5). Moreover, miR-155-5p inhibition increased pyroptosis in PA-treated MPC5 cells, suggesting that miR-155-5p acts as an endogenous stimulator that increases HO-1 expression and reduces pyroptosis. Hence, our findings imply that dapagliflozin inhibits podocyte pyroptosis via the miR-155-5p/HO-1/NLRP3 axis in DM. Furthermore, dapagliflozin substitution may be regarded as an effective strategy for preventing pyroptosis in the kidney, including a therapeutic option for treating pyroptosis-related DN.