Integrated analysis reveals FLI1 regulates the tumor immune microenvironment via its cell-type-specific expression and transcriptional regulation of distinct target genes of immune cells in breast cancer.

BACKGROUND: Immunotherapy is a practical therapeutic approach in breast cancer (BRCA), and the role of FLI1 in immune regulation has gradually been unveiled. However, the specific role of FLI1 in BRCA was conflicted; thus, additional convincing evidence is needed. METHODS: We explored the upstream regulation of FLI1 expression via summary data-based Mendelian randomization (SMR) analysis and ncRNA network construction centering on FLI1 using BRCA genome-wide association study (GWAS) summary data with expression quantitative trait loci (eQTLs) and DNA methylation quantitative trait loci (mQTLs) from the blood and a series of in silico analyses, respectively. We illuminated the downstream function of FLI1 in immune regulation by integrating a series of analyses of single-cell RNA sequence data (scRNA-seq). RESULTS: We verified a causal pathway from FLI1 methylation to FLI1 gene expression to BRCA onset and demonstrated that FLI1 was downregulated in BRCA. FLI1, a transcription factor, served as myeloid and T cells' communication regulator by targeting immune-related ligands and receptor transcription in BRCA tissues. We constructed a ceRNA network centering on FLI1 that consisted of three LncRNAs (CKMT2-AS1, PSMA3-AS1, and DIO3OS) and a miRNA (hsa-miR-324-5p), and the expression of FLI1 was positively related to a series of immune-related markers, including immune cell infiltration, biomarkers of immune cells, and immune checkpoints. CONCLUSION: Low-methylation-induced or ncRNA-mediated downregulation of FLI1 is associated with poor prognosis, and FLI1 might regulate the tumor immune microenvironment via a cell-type-specific target genes manner in BRCA.

Biochar and zero-valent iron alleviated sulfamethoxazole and tetracycline co-stress on the long-term system performance of bioretention cells: Insights into microbial community, antibiotic resistance genes and functional genes.

Antibiotics and antibiotic resistance genes (ARGs), known as emerging contaminants, have raised widespread concern due to their potential environmental and human health risks. In this study, a conventional bioretention cell (C-BRC) and three modified bioretention cells with biochar (BC-BRC), microbial fuel cell coupled/biochar (EBC-BRC) and zero-valent iron/biochar (Fe/BC-BRC) were established and two antibiotics, namely sulfamethoxazole (SMX) and tetracycline (TC), were introduced into the systems in order to thoroughly investigate the co-stress associated with the long-term removal of pollutants, dynamics of microbial community, ARGs and functional genes in wastewater treatment. The results demonstrated that the SMX and TC co-stress significantly inhibited the removal of total nitrogen (TN) (C-BRC: 37.46%; BC-BRC: 41.64%; EBC-BRC: 55.60%) and total phosphorous (TP) (C-BRC: 53.11%; BC-BRC: 55.36%; EBC-BRC: 62.87%) in C-BRC, BC-BRC and EBC-BRC, respectively, while Fe/BC-BRC exhibited profoundly stable and high removal efficiencies (TN: 89.33%; TP: 98.36%). Remarkably, greater than 99% removals of SMX and TC were achieved in three modified BRCs compared with C-BRC (SMX: 30.86 %; TC: 59.29%). The decreasing absolute abundances of denitrifying bacteria and the low denitrification functional genes (nirK: 2.80 × 105-5.97 × 105 copies/g; nirS: 7.22 × 105-1.69 × 106 copies/g) were responsible for the lower TN removals in C-BRC, BC-BRC and EBC-BRC. The amendment of Fe/BC successfully detoxified SMX and TC to functional bacteria. Furthermore, the co-stress of antibiotics stimulated the propagation of ARGs (sulI, sulII, tetA and tetC) in substrates of all BRCs and only Fe/BC-BRC effectively reduced all the ARGs in effluent by an order of magnitude. The findings contribute to developing robust ecological wastewater treatment technologies to simultaneously remove nutrients and multiple antibiotics.

The MYB Transcription Factor GmMYB78 Negatively Regulates Phytophthora sojae Resistance in Soybean.

Phytophthora root rot is a devastating disease of soybean caused by Phytophthora sojae. However, the resistance mechanism is not yet clear. Our previous studies have shown that GmAP2 enhances sensitivity to P. sojae in soybean, and GmMYB78 is downregulated in the transcriptome analysis of GmAP2-overexpressing transgenic hairy roots. Here, GmMYB78 was significantly induced by P. sojae in susceptible soybean, and the overexpressing of GmMYB78 enhanced sensitivity to the pathogen, while silencing GmMYB78 enhances resistance to P. sojae, indicating that GmMYB78 is a negative regulator of P. sojae. Moreover, the jasmonic acid (JA) content and JA synthesis gene GmAOS1 was highly upregulated in GmMYB78-silencing roots and highly downregulated in overexpressing ones, suggesting that GmMYB78 could respond to P. sojae through the JA signaling pathway. Furthermore, the expression of several pathogenesis-related genes was significantly lower in GmMYB78-overexpressing roots and higher in GmMYB78-silencing ones. Additionally, we screened and identified the upstream regulator GmbHLH122 and downstream target gene GmbZIP25 of GmMYB78. GmbHLH122 was highly induced by P. sojae and could inhibit GmMYB78 expression in resistant soybean, and GmMYB78 was highly expressed to activate downstream target gene GmbZIP25 transcription in susceptible soybean. In conclusion, our data reveal that GmMYB78 triggers soybean sensitivity to P. sojae by inhibiting the JA signaling pathway and the expression of pathogenesis-related genes or through the effects of the GmbHLH122-GmMYB78-GmbZIP25 cascade pathway.

Global characterization of B cell receptor repertoire in COVID-19 patients by single-cell V(D)J sequencing.

The world is facing a pandemic of Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Adaptive immune responses are essential for SARS-CoV-2 virus clearance. Although a large body of studies have been conducted to investigate the immune mechanism in COVID-19 patients, we still lack a comprehensive understanding of the BCR repertoire in patients. In this study, we used the single-cell V(D)J sequencing to characterize the BCR repertoire across convalescent COVID-19 patients. We observed that the BCR diversity was significantly reduced in disease compared with healthy controls. And BCRs tend to skew toward different V gene segments in COVID-19 and healthy controls. The CDR3 sequences of heavy chain in clonal BCRs in patients were more convergent than that in healthy controls. In addition, we discovered increased IgG and IgA isotypes in the disease, including IgG1, IgG3 and IgA1. In all clonal BCRs, IgG isotypes had the most frequent class switch recombination events and the highest somatic hypermutation rate, especially IgG3. Moreover, we found that an IgG3 cluster from different clonal groups had the same IGHV, IGHJ and CDR3 sequences (IGHV4-4-CARLANTNQFYDSSSYLNAMDVW-IGHJ6). Overall, our study provides a comprehensive characterization of the BCR repertoire in COVID-19 patients, which contributes to the understanding of the mechanism for the immune response to SARS-CoV-2 infection.

PLIN2 promotes HCC cells proliferation by inhibiting the degradation of HIF1α.

PLIN2 has been found to be dysregulated in several human malignancies, which influences cancer progression. However, the roles of PLIN2 in regulating hepatocellular carcinoma (HCC) progression are still unclear. Here, we revealed that PLIN2 was frequently upregulated in HCC cells and tissues, and increased PLIN2 expression was associated with poor prognosis outcomes in HCC. In HCC cells, overexpressing PLIN2 promoted cell proliferation, PLIN2-deficiency inhibited cell vitality. Mechanistically, silencing of PLIN2 expression downregulated hypoxia inducible factor 1-α (HIF1α) expression and this downregulation in turn inhibited the targeting genes of HIF1α. Furthermore, we found that PLIN2 stabilized and retarded the degradation of the HIF1α through autophagy-lysosomal pathway by inhibiting AMPK/ULK1. Collectively, we clarified the carcinogenic role of PLIN2 in HCC and suggested a prognostic biomarker for diagnosis and clinical therapy in the future.

Spatiotemporal evolution of soil water erosion in Ningxia grassland based on the RUSLE-TLSD model.

Accurate assessment of grassland soil erosion before and after grazing exclusion and revealing its driving mechanism are the basis of grassland risk management. In this study, the long-term soil erosion in Ningxia grassland was simulated by integrating and calibrating the transport limited sediment delivery (TLSD) function with the revised universal soil loss equation (RUSLE) model. The differential mechanisms of soil loss were explored using the GeoDetector method, and the relative effects of precipitation changes (PC) and human activities (HA) on grassland soil erosion were investigated using double mass curves. The measured sediment discharges from six hydrological stations verified that the RUSLE-TLSD model could reliably simulate water erosion in Ningxia. From 1988 to 2018, the water erosion rate of grassland in Ningxia ranged from 74.98 to 14.98 t⋅ha-1⋅a-1, showing an overall downward trend. July to September is the period with the highest of water erosion. The slope is the dominant factor influencing the spatial distribution of water erosion. After grazing exclusion, the net water erosion rate in Ningxia grassland and sub-regions decreased significantly. The double mass curves results show that human activities were the main driver of net erosion reduction. The focus of water erosion control in Ningxia is to control soil erosion in different terrains and protect grassland with slopes greater than 10°.

Multi-Parameter Optimization of Rubidium Laser Optically Pumped Magnetometers with Geomagnetic Field Intensity.

Rubidium laser optically pumped magnetometers (OPMs) are widely used magnetic sensors based on the Zeeman effect, laser pumping, and magnetic resonance principles. They measure the magnetic field by measuring the magnetic resonance signal passing through a rubidium atomic gas cell. The quality of the magnetic resonance signal is a necessary condition for a magnetometer to achieve high sensitivity. In this research, to obtain the best magnetic resonance signal of rubidium laser OPMs in the Earth's magnetic field intensity, the experiment system of rubidium laser OPMs is built with a rubidium atomic gas cell as the core component. The linewidth and amplitude ratio (LAR) of magnetic resonance signals is utilized as the optimization objective function. The magnetic resonance signals of the magnetometer experiment system are experimentally measured for different laser frequencies, radio frequency (RF) intensities, laser powers, and atomic gas cell temperatures in a background magnetic field of 50,765 nT. The experimental results indicate that optimizing these parameters can reduce the LAR by one order of magnitude. This shows that the optimal parameter combination can effectively improve the sensitivity of the magnetometer. The sensitivity defined using the noise spectral density measured under optimal experimental parameters is 1.5 pT/Hz1/2@1 Hz. This work will provide key technical support for rubidium laser OPMs' product development.

Highly oriented platinum/iridium thin films for high-temperature thermocouples with superior precision.

The long-term precise high-temperature measurement of thin-film thermocouples (TFTCs) has attracted attention due to the capability of instantaneous temperature detection. However, related technologies have seen slow development, and there is no one standard TFTC yet. Here, we focus on a new strategy of reducing alloys for the easy preparation and performance enhancement of TFTCs via nanostructure and interface design. To this end, we fabricated a platinum/iridium (Pt/Ir) pure-element TFTC with a well matched interface and few defects, which demonstrated excellent long-term service stability over a high-temperature range. The corresponding polynomial fitting coefficients were ≥0.99999, indicating the accurate acquisition of temperature data. A reduced deviation (<0.21%) between three calibration cycles was obtained over a wide temperature range of 300 °C to 1000 °C, which is better than the maximum precision of a standard wire thermocouple. Superior properties are achieved because of the resulting fewer defects in the Pt and Ir thin films with highly preferential orientation along the (111) plane. The results indicate that our Pt/Ir TFTCs have significant potential for application in many domains such as thermal detection, microelectronics and aero-engines.

Defect governed zinc-rich columnar AZO thin film and contact interface for enhanced performance of thermocouples.

The research on the stable thermoelectric properties and contact interface of high-precision thin-film thermocouples lags far behind the demand. In this study, a zinc-rich Al-doped ZnO (AZO) thin film was fabricated, in which the carriers were mainly donated by the Al dopant, and the oxygen defects migrated together, forming cage defects. Then, an indium tin oxide (ITO)/AZO thin-film thermocouple was prepared. It had a special temperature-dependent voltage curve due to the effects of cage defects on the thermoelectric properties of the AZO thin film and interfacial electron diffusion. When the zinc atoms in the cage defects were excited after annealing, a linear relationship between the temperature and voltage was obtained. The Seebeck coefficient of the thermocouple was constant at 168 µV K-1 over the entire measured temperature range. In addition, the calculated error of the thermocouple was lower than 1% from 50 °C to 500 °C, showing good repeatability. These results showed that defect engineering could effectively be used to improve the temperature range stability of thermoelectric materials and optimize the precision of thin-film thermocouples.

Comprehensive analysis of TCR repertoire in COVID-19 using single cell sequencing.

T-cell receptor (TCR) is crucial in T cell-mediated virus clearance. To date, TCR bias has been observed in various diseases. However, studies on the TCR repertoire of COVID-19 patients are lacking. Here, we used single-cell V(D)J sequencing to conduct comparative analyses of TCR repertoire between 12 COVID-19 patients and 6 healthy controls, as well as other virus-infected samples. We observed distinct T cell clonal expansion in COVID-19. Further analysis of VJ gene combination revealed 6 VJ pairs significantly increased, while 139 pairs significantly decreased in COVID-19 patients. When considering the VJ combination of α and ß chains at the same time, the combination with the highest frequency on COVID-19 was TRAV12-2-J27-TRBV7-9-J2-3. Besides, preferential usage of V and J gene segments was also observed in samples infected by different viruses. Our study provides novel insights on TCR in COVID-19, which contribute to our understanding of the immune response induced by SARS-CoV-2.

Condensed Osmaquinolines with NIR-II Absorption Synthesized by Aryl C-H Annulation and Aromatization.

The structural design and tuning of properties of metallaaromatics are crucial in materials and energy science. Herein, we describe the rapid synthesis of tetracyclic metallaaromatics containing quinoline and pentalene motifs fused by a metal-bridged fragment. These unique compounds display remarkably broad absorption, enabling for the first time the absorption of metallaaromatics to reach the second near-infrared (NIR-II) bio-window. The formation of osmaquinoline unit involves an unconventional C(sp2 )-C(sp3 ) coupling promoted by AgBF4 to achieve [3+3] cycloaddition. The introduction of cyclic dπ -pπ conjugation and extension of the aromatic π-framework can effectively shrink the HOMO-LUMO gap, thus broadening the absorption window. The considerable photothermal conversion efficiency (PCE) in both the NIR-I and NIR-II windows, the high photothermal stability and the excellent electrochemical behavior suggest many potential applications of these condensed metallaquinolines.

Alternative splicing associated with cancer stemness in kidney renal clear cell carcinoma.

BACKGROUD: Cancer stemness is associated with metastases in kidney renal clear cell carcinoma (KIRC) and negatively correlates with immune infiltrates. Recent stemness evaluation methods based on the absolute expression have been proposed to reveal the relationship between stemness and cancer. However, we found that existing methods do not perform well in assessing the stemness of KIRC patients, and they overlooked the impact of alternative splicing. Alternative splicing not only progresses during the differentiation of stem cells, but also changes during the acquisition of the stemness features of cancer stem cells. There is an urgent need for a new method to predict KIRC-specific stemness more accurately, so as to provide help in selecting treatment options. METHODS: The corresponding RNA-Seq data were obtained from the The Cancer Genome Atlas (TCGA) data portal. We also downloaded stem cell RNA sequence data from the Progenitor Cell Biology Consortium (PCBC) Synapse Portal. Independent validation sets with large sample size and common clinic pathological characteristics were obtained from the Gene Expression Omnibus (GEO) database. we constructed a KIRC-specific stemness prediction model using an algorithm called one-class logistic regression based on the expression and alternative splicing data to predict stemness indices of KIRC patients, and the model was externally validated. We identify stemness-associated alternative splicing events (SASEs) by analyzing different alternative splicing event between high- and low- stemness groups. Univariate Cox and multivariable logistic regression analysisw as carried out to detect the prognosis-related SASEs respectively. The area under curve (AUC) of receiver operating characteristic (ROC) was performed to evaluate the predictive values of our model. RESULTS: Here, we constructed a KIRC-specific stemness prediction model with an AUC of 0.968,and to provide a user-friendly interface of our model for KIRC stemness analysis, we have developed KIRC Stemness Calculator and Visualization (KSCV), hosted on the Shiny server, can most easily be accessed via web browser and the url https://jiang-lab.shinyapps.io/kscv/ . When applied to 605 KIRC patients, our stemness indices had a higher correlation with the gender, smoking history and metastasis of the patients than the previous stemness indices, and revealed intratumor heterogeneity at the stemness level. We identified 77 novel SASEs by dividing patients into high- and low- stemness groups with significantly different outcome and they had significant correlations with expression of 17 experimentally validated splicing factors. Both univariate and multivariate survival analysis demonstrated that SASEs closely correlated with the overall survival of patients. CONCLUSIONS: Basing on the stemness indices, we found that not only immune infiltration but also alternative splicing events showed significant different at the stemness level. More importantly, we highlight the critical role of these differential alternative splicing events in poor prognosis, and we believe in the potential for their further translation into targets for immunotherapy.

LncRNA Gm16410 regulates PM2.5-induced lung Endothelial-Mesenchymal Transition via the TGF-ß1/Smad3/p-Smad3 pathway.

Exposure to PM2.5 can cause serious harm to the respiratory system. Until now, although many toxicological studies have shown that pulmonary fibrosis can be caused by long-term PM2.5 exposure, there is no evidence that Endothelial-Mesenchymal Transition (EndMT) can trigger the process of pulmonary fibrosis after exposure. LncRNAs are a class of non-coding RNAs detected in mammalian cells. Nevertheless, researchers have not found whether lncRNAs participate in PM2.5 induced EndMT during pathophysiological duration. The Balb/c mouse model was exposed to PM2.5 for 4 months by dynamic intoxication. The levels of specific endothelial and mesenchymal markers were evaluated by molecular biology experiments to elucidate the mechanisms of EndMT induced by PM2.5 in lung tissues. LncRNA microarray analysis of the established mouse model of PM2.5 exposure was performed. Based on a bioinformatics analysis and RT-qPCR analysis, lncRNA Gm16410 attracted our attention. The change of lncRNA Gm16410 in mouse pulmonary vascular endothelial cells (MHCs) exposed to PM2.5 was verified, and the mechanism of lncRNA Gm16410 in EndMT was discussed. The changes of cell function were evaluated by cell migration and proliferation experiments. The molecular biology experiments proved that PM2.5 induced EndMT by activating the TGF-ß1/Smad3/p-Smad3 pathway in vitro. The relationship of EndMT and lncRNA Gm16410 was verified in mouse lung tissues and MHC cells by PM2.5 exposure. The involvement of lncRNA Gm16410 in PM2.5-induced EndMT highlights the potential of lncRNA to promote pulmonary fibrosis under environmental pollution.

The synergistic antitumor effect of Huaier combined with 5-Florouracil in human cholangiocarcinoma cells.

BACKGROUND: 5-Florouracil (5-FU) is a commonly used chemotherapeutic drug for cholangiocarcinoma, whereas it has unsatisfactory effect, and patients often have chemo-resistance to it. The combination of chemotherapeutic agents and traditional Chinese medicine has already exhibited a promising application in oncotherapy. Huaier extract (Huaier) has been used in clinical practice widely, exhibiting good anti-tumor effect. This paper aims to investigate the possibility of combination 5-FU and Huaier as a treatment for cholangiocarcinoma. METHODS: A series of experiments were performed on the Huh28 cells in vitro, which involved cell proliferation, colony formation, apoptosis, cell cycle, migratory and invasive tests. Besides, western blots were also performed to examine the potential mechanism of 5-FU. RESULTS: The combination effect (antagonism, synergy or additive) was assessed using Chou-Talalay method. Using the CCK-8 and Colony formation assay, the anti-proliferation effect of 5-FU combined with Huaier was observed. Apoptosis inducing and cell cycle arrest effect of the combination of two drugs were assessed by flow cytometry. To determine the combined treatment on cell immigration and invasion ability, wound healing and Transwell assay were performed. The above experiment results suggest that the combined 5-FU and Huaier, compared with treatment using either drug alone, exhibited stronger effects in anti-proliferation, cycle arrest, apoptosis-induced and anti-metastasis. Further, western blot results reveal that the inhibition of STAT3 and its target genes (e.g. Ki67, Cyclin D1, Bcl-2 and MMP-2) might be set as the potential therapeutic targets. Besides, the inhibition of combination treatment in proteins expression associated with proliferation, apoptosis, cell cycle and metastasis was consistent with that of previous phenotypic experiments. CONCLUSIONS: Huaier combined with 5-FU exhibited a synergistic anti-tumor effect in Huh28 cell. Furthermore, the mechanisms might be associated with the activation and translocation of STAT3, as well as its downstream genes.

Graphene Quantum Dots-Capped Magnetic Mesoporous Silica Nanoparticles as a Multifunctional Platform for Controlled Drug Delivery, Magnetic Hyperthermia, and Photothermal Therapy.

A multifunctional platform is reported for synergistic therapy with controlled drug release, magnetic hyperthermia, and photothermal therapy, which is composed of graphene quantum dots (GQDs) as caps and local photothermal generators and magnetic mesoporous silica nanoparticles (MMSN) as drug carriers and magnetic thermoseeds. The structure, drug release behavior, magnetic hyperthermia capacity, photothermal effect, and synergistic therapeutic efficiency of the MMSN/GQDs nanoparticles are investigated. The results show that monodisperse MMSN/GQDs nanoparticles with the particle size of 100 nm can load doxorubicin (DOX) and trigger DOX release by low pH environment. Furthermore, the MMSN/GQDs nanoparticles can efficiently generate heat to the hyperthermia temperature under an alternating magnetic field or by near infrared irradiation. More importantly, breast cancer 4T1 cells as a model cellular system, the results indicate that compared with chemotherapy, magnetic hyperthermia or photothermal therapy alone, the combined chemo-magnetic hyperthermia therapy or chemo-photothermal therapy with the DOX-loaded MMSN/GQDs nanosystem exhibits a significant synergistic effect, resulting in a higher efficacy to kill cancer cells. Therefore, the MMSN/GQDs multifunctional platform has great potential in cancer therapy for enhancing the therapeutic efficiency.

Microecological regulation in HCC therapy: Gut microbiome enhances ICI treatment.

The exploration of the complex mechanisms of cancer immunotherapy is rapidly evolving worldwide, and our focus is on the interaction of hepatocellular carcinoma (HCC) with immune checkpoint inhibitors (ICIs), particularly as it relates to the regulatory role of the gut microbiome. An important basis for the induction of immune responses in HCC is the presence of specific anti-tumor cells that can be activated and reinforced by ICIs, which is why the application of ICIs results in sustained tumor response rates in the majority of HCC patients. However, mechanisms of acquired resistance to immunotherapy in unresectable HCC result in no long-term benefit for some patients. The significant heterogeneity of inter-individual differences in the gut microbiome in response to treatment with ICIs makes it possible to target modulation of specific gut microbes to assist in augmenting checkpoint blockade therapies in HCC. This review focuses on the complex relationship between the gut microbiome, host immunity, and HCC, and emphasizes that manipulating the gut microbiome to improve response rates to cancer ICI therapy is a clinical strategy with unlimited potential.

Identification of gut microbes-related molecular subtypes and their biomarkers in colorectal cancer.

The role of gut microbes (GM) and their metabolites in colorectal cancer (CRC) development has attracted increasing attention. Several studies have identified specific microorganisms that are closely associated with CRC occurrence and progression, as well as key genes associated with gut microorganisms. However, the extent to which gut microbes-related genes can serve as biomarkers for CRC progression or prognosis is still poorly understood. This study used a bioinformatics-based approach to synthetically analyze the large amount of available data stored in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Through this analysis, this study identified two distinct CRC molecular subtypes associated with GM, as well as CRC markers related to GM. In addition, these new subtypes exhibit significantly different survival outcomes and are characterized by distinct immune landscapes and biological functions. Gut microbes-related biomarkers (GMRBs), IL7 and BCL10, were identified and found to have independent prognostic value and predictability for immunotherapeutic response in CRC patients. In addition, a systematic collection and review of prior research literature on GM and CRC provided additional evidence to support these findings. In conclusion, this paper provides new insights into the underlying pathological mechanisms by which GM promotes the development of CRC and suggests potentially viable solutions for individualized prevention, screening, and treatment of CRC.

Multi-omics pan-cancer study of SPTBN2 and its value as a potential therapeutic target in pancreatic cancer.

SPTBN2 is a protein-coding gene that is closely related to the development of malignant tumors. However, its prognostic value and biological function in pan-cancer, especially pancreatic cancer (PAAD), have not been reported. In the present study, a novel exploration of the value and potential mechanism of SPTBN2 in PAAD was conducted using multi-omics in the background of pan-cancer. Via various database analysis, up-regulated expression of SPTBN2 was detected in most of the tumor tissues examined. Overexpression of SPTBN2 in PAAD and kidney renal clear cell cancer patients potentially affected overall survival, disease-specific survival, and progression-free interval. In PAAD, SPTBN2 can be used as an independent factor affecting prognosis. Mutations and amplification of SPTBN2 were detected, with abnormal methylation of SPTBN2 affecting its expression and the survival outcome of PAAD patients. Immunoassay results demonstrate that SPTBN2 was a potential biomarker for predicting therapeutic response in PAAD, and may influence the immunotherapy efficacy of PAAD by regulating levels of CD8 + T cells and neutrophil infiltration. Results from an enrichment analysis indicated that SPTBN2 may regulate the development of PAAD via immune pathways. Thus, SPTBN2 is a potential prognostic biomarker and immunotherapy target based on its crucial role in the development of PAAD.

Effects of NLRP3 Inflammasome Mediated Pyroptosis on Cardiovascular Diseases and Intervention Mechanism of Chinese Medicine.

Activation of the NOD-like receptor protein 3 (NLRP3) inflammasome signaling pathway is an important mechanism underlying myocardial pyroptosis and plays an important role in inflammatory damage to myocardial tissue in patients with cardiovascular diseases (CVDs), such as diabetic cardiomyopathy, ischemia/reperfusion injury, myocardial infarction, heart failure and hypertension. Noncoding RNAs (ncRNAs) are important regulatory factors. Many Chinese medicine (CM) compounds, including their effective components, can regulate pyroptosis and exert myocardium-protecting effects. The mechanisms underlying this protection include inhibition of inflammasome protein expression, Toll-like receptor 4-NF-κB signal pathway activation, oxidative stress, endoplasmic reticulum stress (ERS), and mixed lineage kinase 3 expression and the regulation of silent information regulator 1. The NLRP3 protein is an important regulatory target for CVD prevention and treatment with CM. Exploring the effects of the interventions mediated by CM and the related mechanisms provides new ideas and perspectives for CVD prevention and treatment.

Computed tomography-based intermuscular adipose tissue analysis and its predicting role in post-kidney transplantation diabetes mellitus.

BACKGROUND: While body mass index (BMI) is the most widely used indicator as a measure of obesity factors in post-transplantation diabetes mellitus (PTDM), body composition is a more accurate measure of obesity. This study aims to investigate the effects of Computed tomography (CT)--based morphemic factors on PTDM and establish a prediction model for PTDM after kidney transplantation. METHODS: The pre-transplant data and glycemic levels of kidney transplant recipients (June 2021 to July 2023) were retrospectively and prospectively collected. Univariate and multivariate analyses were conducted to analyze the relationship between morphemic factors and PTDM at one month, six months, and one year after hospital discharge. Subsequently, a one-year risk prediction model based on morphemic factors was developed. RESULTS: The study consisted of 131 participants in the one-month group, where Hemoglobin A1c (HbA1c) (p = 0.02) was identified as the risk factor for PTDM. In the six-month group, 129 participants were included, and the intermuscular adipose tissue (IMAT) area (p = 0.02) was identified as the risk factor for PTDM. The one-year group had 128 participants, and the risk factors for PTDM were identified as body mass index (BMI) (p = 0.02), HbA1c (p = 0.01), and IMAT area (p = 0.007). HbA1c (%) and IMAT area were included in the risk prediction Model for PTDM in the one-year group with AUC = 0.716 (95 % CI 0.591-0.841, p = 0.001). CONCLUSIONS: Compared to BMI and other morphemic factors, this study demonstrated that the IMAT area was the most potential predictor of PTDM. CLINICAL TRIAL NOTATION: Chictr.org (ChiCTR2300078639).