Sarcopenia is a prognostic factor in lymphoma patients: a systematic review and meta-analysis.

Findings regarding the relationship between sarcopenia and lymphoma have been inconsistent across studies. This study investigated the association between sarcopenia and lymphoma. We systematically searched the Embase, Science Direct, Cochrane Library, and PubMed databases from inception to 31 March 2024 to identify relevant studies. Two researchers independently extracted and evaluated studies that met inclusion and exclusion criteria. Twenty-six studies with 3659 participants were included. Sarcopenic lymphoma patients had poor overall survival (OS) (HR = 1.88; 95% CI: 1.47-2.41; p < 0.001). The heterogeneity was high (I2=80%). However, the result of the Egger test indicated a significant publication bias (p < 0.001). After employing the trim and fill method to adjust for this bias, the HR of OS became non-significant (p > 0.05). The progression-free survival (PFS) was worse in sarcopenic patients (HR = 1.77; 95% CI: 1.37-2.29; p < 0.001; I2=70%). There was no significant publication bias (p > 0.05). In the subgroup analyses, sarcopenia was a negative predictor of OS in lymphoma patients who undergo hematopoietic cell transplantation (HCT) (HR  = 1.61;95% CI: 1.19-2.18; I2=30%). Male lymphoma patients with sarcopenia had a significantly worse OS (HR = 2.29; 95% CI:1.24-4.24; p = 0.009). Among patients with primary central nervous system lymphoma (PCNSL), those with sarcopenia defined by temporal muscle thickness (TMT) exhibited significantly worse OS (HR = 2.20; 95% CI:1.04-4.65; p = 0.039; I2=68%). Sarcopenia is associated with worse PFS in lymphoma patients. Subgroup analyses indicate that sarcopenia is a negative predictor of OS after HCT, and male lymphoma patients who suffer from sarcopenia have higher mortality. Sarcopenia defined by TMT is also a negative predictor of OS for patients with PCNSL.

RNA demethylase FTO participates in malignant progression of gastric cancer by regulating SP1-AURKB-ATM pathway.

Gastric cancer (GC) is the 5th most prevalent cancer and the 4th primary cancer-associated mortality globally. As the first identified m6A demethylase for removing RNA methylation modification, fat mass and obesity-associated protein (FTO) plays instrumental roles in cancer development. Therefore, we study the biological functions and oncogenic mechanisms of FTO in GC tumorigenesis and progression. In our study, FTO expression is obviously upregulated in GC tissues and cells. The upregulation of FTO is associated with advanced nerve invasion, tumor size, and LNM, as well as the poor prognosis in GC patients, and promoted GC cell viability, colony formation, migration and invasion. Mechanistically, FTO targeted specificity protein 1 and Aurora Kinase B, resulting in the phosphorylation of ataxia telangiectasia mutated and P38 and dephosphorylation of P53. In conclusion, the m6A demethylase FTO promotes GC tumorigenesis and progression by regulating the SP1-AURKB-ATM pathway, which may highlight the potential of FTO as a diagnostic biomarker for GC patients' therapy response and prognosis.

Effect of Roasting on the Chemical Composition and Oxidative Stability of Tomato (Solanum lycopersicum L.) Seed Oil.

In this study, tomato seed (TS) samples were subjected to different roasting conditions (90-170 °C and 10-30 min) to compare their effects on the chemical composition and oxidative stability of tomato seed oil (TSO). Unroasted TS was considered as a control sample. Our results revealed that moderate roasting (130 °C/20 min) can significantly increase the content of linoleic acid (54.01-54.89%), linolenic acid (2.17-2.41%), phytosterols (2789.56-3037.31 mg/kg), squalene (5.06-13.10 mg/kg), total phenols (22.37-22.67 mg GAE/100 g), and other functional components (p < 0.05) in TSO, while the antioxidant activity (via DPPH, ABTS, and FRAP assays) also increased. In addition, the tocopherol content decreased significantly (758.53-729.50 mg/kg). Accelerated oxidation experiments showed that roasting (170 °C/30 min) increased the oxidative stability index (OSI) of TSO from 5.35 to 7.07 h (p < 0.05). Furthermore, roasting gradually increased the content of 5-hydroxymethylfurfural (HMF) (0-1.74 mg/kg), which indicates that the oxidative stability and the degree of the Maillard reaction increased upon roasting. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) showed that moderate roasting (130 °C/20 min) improved the chemical composition, antioxidant activity, and oxidative stability of TSO. Furthermore, this work provides a useful theoretical basis for the processing and wide application of TSO in the pharmaceutical and food industries.

The risk of endocrine immune-related adverse events induced by PD-1 inhibitors in cancer patients: a systematic review and meta-analysis.

Objective: Endocrinopathies are the most common immune-related adverse events (irAEs) observed during therapy with PD-1 inhibitors. In this study, we conducted a comprehensive systematic review and meta-analysis to evaluate the risk of immune-related endocrinopathies in patients treated with PD-1 inhibitors. Methods: We performed a systematic search in the PubMed, Embase, and Cochrane Library databases to retrieve all randomized controlled trials (RCTs) involving PD-1 inhibitors, spanning from their inception to November 24, 2023. The comparative analysis encompassed patients undergoing chemotherapy, targeted therapy, or receiving placebo as control treatments. This study protocol has been registered with PROSPERO (CRD42023488303). Results: A total of 48 clinical trials comprising 24,514 patients were included. Compared with control groups, patients treated with PD-1 inhibitors showed an increased risk of immune-related adverse events, including hypothyroidism, hyperthyroidism, hypophysitis, thyroiditis, diabetes mellitus, and adrenal insufficiency. Pembrolizumab was associated with an increased risk of all aforementioned endocrinopathies (hypothyroidism: RR=4.76, 95%CI: 3.55-6.39; hyperthyroidism: RR=9.69, 95%CI: 6.95-13.52; hypophysitis: RR=5.47, 95%CI: 2.73-10.97; thyroiditis: RR=5.95, 95%CI: 3.02-11.72; diabetes mellitus: RR=3.60, 95%CI: 1.65-7.88; adrenal insufficiency: RR=4.80, 95%CI: 2.60-8.88). Nivolumab was associated with an increased risk of hypothyroidism (RR=7.67, 95%CI: 5.00-11.75) and hyperthyroidism (RR=9.22, 95%CI: 4.71-18.04). Tislelizumab and sintilimab were associated with an increased risk of hypothyroidism (RR=19.07, 95%CI: 5.46-66.69 for tislelizumab and RR=18.36, 95%CI: 3.58-94.21 for sintilimab). For different tumor types, both hypothyroidism and hyperthyroidism were at high risks. Besides, patients with non-small cell lung cancer were at a higher risk of thyroiditis and adrenal insufficiency. Patients with melanoma were at a higher risk of hypophysitis and diabetes mellitus. Both low- and high-dose group increased risks of hypothyroidism and hyperthyroidism. Conclusion: Risk of endocrine irAEs may vary in different PD-1 inhibitors and different tumor types. Increased awareness and understanding of the risk features of endocrine irAEs associated with PD-1 inhibitors is critical for clinicians. Systematic review registration: crd.york.ac.uk/prospero, identifier PROSPERO (CRD42023488303).

Influenza A virus infection disrupts the function of syncytiotrophoblast cells and contributes to adverse pregnancy outcomes.

Pregnancy heightens susceptibility to influenza A virus (IAV) infection, thereby increasing the risk of severe pneumonia and maternal mortality. It also raises the chances of adverse outcomes in offspring, such as fetal growth restriction, preterm birth, miscarriage, and stillbirth in offsprings. However, the underlying mechanisms behind these effects remain largely unknown. Syncytiotrophoblast cells, crucial in forming the placental barrier, nutrient exchange and hormone secretion, have not been extensively studied for their responses to IAV. In our experiment, we used Forskolin-treated BeWo cells to mimic syncytiotrophoblast cells in vitro, and infected them with H1N1, H5N1 and H7N9 virus stains. Our results showed that syncytiotrophoblast cells, with their higher intensity of sialic acid receptors, strongly support IAV infection and replication. Notably, high-dose viral infection and prolonged exposure resulted in a significant decrease in fusion index, as well as gene and protein expression levels associated with trophoblast differentiation, ß-human chorionic gonadotropin secretion, estrogen and progesterone biosynthesis, and nutrient transport. In pregnant BALB/c mice infected with the H1N1 virus, we observed significant decreases in trophoblast differentiation and hormone secretion gene expression levels. IAV infection also resulted in preterm labor, fetal growth restriction, and increased maternal and fetal morbidity and mortality. Our findings indicate that IAV infection in syncytiotrophoblastic cells can result in adverse pregnancy outcomes by altering trophoblast differentiation, suppressing of ß-hCG secretion, and disrupting placental barrier function.

Elemental Characterization of Ambient Particulate Matter for a Globally Distributed Monitoring Network: Methodology and Implications.

Global ground-level measurements of elements in ambient particulate matter (PM) can provide valuable information to understand the distribution of dust and trace elements, assess health impacts, and investigate emission sources. We use X-ray fluorescence spectroscopy to characterize the elemental composition of PM samples collected from 27 globally distributed sites in the Surface PARTiculate mAtter Network (SPARTAN) over 2019-2023. Consistent protocols are applied to collect all samples and analyze them at one central laboratory, which facilitates comparison across different sites. Multiple quality assurance measures are performed, including applying reference materials that resemble typical PM samples, acceptance testing, and routine quality control. Method detection limits and uncertainties are estimated. Concentrations of dust and trace element oxides (TEO) are determined from the elemental dataset. In addition to sites in arid regions, a moderately high mean dust concentration (6 µg/m3) in PM2.5 is also found in Dhaka (Bangladesh) along with a high average TEO level (6 µg/m3). High carcinogenic risk (>1 cancer case per 100000 adults) from airborne arsenic is observed in Dhaka (Bangladesh), Kanpur (India), and Hanoi (Vietnam). Industries of informal lead-acid battery and e-waste recycling as well as coal-fired brick kilns likely contribute to the elevated trace element concentrations found in Dhaka.

Frontline and Relapsed Rhabdomyosarcoma (FAR-RMS) Clinical Trial: A Report from the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG).

The Frontline and Relapsed Rhabdomyosarcoma (FaR-RMS) clinical trial is an overarching, multinational study for children and adults with rhabdomyosarcoma (RMS). The trial, developed by the European Soft Tissue Sarcoma Study Group (EpSSG), incorporates multiple different research questions within a multistage design with a focus on (i) novel regimens for poor prognostic subgroups, (ii) optimal duration of maintenance chemotherapy, and (iii) optimal use of radiotherapy for local control and widespread metastatic disease. Additional sub-studies focusing on biological risk stratification, use of imaging modalities, including [18F]FDG PET-CT and diffusion-weighted MRI imaging (DWI) as prognostic markers, and impact of therapy on quality of life are described. This paper forms part of a Special Issue on rhabdomyosarcoma and outlines the study background, rationale for randomisations and sub-studies, design, and plans for utilisation and dissemination of results.

HTRA1 promotes EMT through the HDAC6/Ac-α-tubulin pathway in human GBM cells.

BACKGROUND: The infiltrative nature of human gliomas renders complete surgical removal of tumors futile. Thus, illuminating mechanisms of their infiltrative properties may improve therapies and outcomes of glioma patients. METHODS: Comprehensive bioinformatic analyses of PRSS family were undertaken. Transfection of HTRA1 siRNAs was used to suppress HTRA1 expression. CCK-8, EdU, and colony formation assay were employed to assess cell viability, and cell migration/invasion was detected by transwell, wound healing, and 3D tumor spheroid invasion assays. Immunoprecipitation was applied to study the mechanism that HTRA1 affected cell migration. In addition, in situ xenograft tumor model was employed to explore the role of HTRA1 in glioma growth in vivo. RESULTS: HTRA1 knockdown could lead to suppression of cell viability, migration and invasion, as well as increased apoptosis. Immunoprecipitation results indicates HTRA1 might facilitate combination between HDAC6 and α-tubulin to enhance cell migration by decreasing α-tubulin acetylation. Besides, HTRA1 knockdown inhibited the growth of xenografts derived from orthotopic implantation of GBM cells and prolonged the survival time of tumor-bearing mice. CONCLUSION: Our results indicate that HTRA1 promotes the proliferation and migration of GBM cells in vitro and in vivo, and thus may be a potential target for treatment in gliomas.

Effect of anti-COVID-19 drugs on patients with cancer.

The clinical treatment of patients with cancer who are also diagnosed with coronavirus disease (COVID-19) has been a challenging issue since the outbreak of COVID-19. Therefore, it is crucial to understand the effects of commonly used drugs for treating COVID-19 in patients with cancer. Hence, this review aims to provide a reference for the clinical treatment of patients with cancer to minimize the losses caused by the COVID-19 pandemic. In this study, we also focused on the relationship between COVID-19, commonly used drugs for treating COVID-19, and cancer. We specifically investigated the effect of these drugs on tumor cell proliferation, migration, invasion, and apoptosis. The potential mechanisms of action of these drugs were discussed and evaluated. We found that most of these drugs showed inhibitory effects on tumors, and only in a few cases had cancer-promoting effects. Furthermore, inappropriate usage of these drugs may lead to irreversible kidney and heart damage. Finally, we have clarified the use of different drugs, which can provide useful guidance for the clinical treatment of cancer patients diagnosed with COVID-19.

Correlation of IVIM/DKI Parameters with Hypoxia Biomarkers in Fibrosarcoma Murine Models: Direct Control of MRI and Pathological Sections.

RATIONALE AND OBJECTIVES: To investigate whether intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) parameters correlate with hypoxia biomarkers, namely hypoxia inducible factor-1ɑ (HIF-1ɑ), carbonic anhydrase IX (CAIX), and pimonidazole (PIMO), in fibrosarcoma (FS) murine models. MATERIALS AND METHODS: A model of 30 FS nude mice was established. All mice underwent magnetic resonance imaging (MRI) scans after which the IVIM (standard apparent diffusion coefficient [standard ADC], pure diffusion coefficient [D], pseudo-diffusion coefficient [D*], and perfusion fraction [f]) and DKI parameters (mean diffusion [MD], mean kurtosis [MK]) were obtained. Based on an MRI-pathology controlled method, correlations between each MRI parameter and hypoxia biomarkers were assessed by Pearson or Spearman tests. An independent sample t-test or Wilcoxon's rank sum test, and receiver operating characteristic curves were used to identify whether MRI parameters could differentiate between high and low expressions of hypoxia biomarkers. RESULTS: The IVIM/DKI parameters showed varying degrees of correlation with HIF-1α, CAIX, and PIMO expression. Among them, the D, f, and MK values could confirm HIF-1α expression, while D, f, and MK values could assess CAIX expression. Finally, standard D and MK values could evaluate PIMO expression levels. CONCLUSION: IVIM and DKI parameters can be used to reflect hypoxic biomarkers of FS and have the potential to detect tumor hypoxia.

Immune profiling of pancreatic cancer for radiotherapy with immunotherapy and targeted therapy: Biomarker analysis of a randomized phase 2 trial.

PURPOSE: Immunotherapy alone offered limited survival benefits in pancreatic cancer, while the role of immunotherapy-centric combined therapy remains controversial. Therefore, it is required to develop biomarkers to precisely deliver immunotherapy-based multimodality for pancreatic cancer. METHODS: This is a secondary analysis of an open label, randomized, phase 2 trial, whereas patients with locally recurrent pancreatic cancer after surgery were enrolled. Eligible patients with mutant KRAS and positive immunohistochemical staining of PD-L1 were randomly assigned to receive stereotactic body radiation therapy (SBRT) plus pembrolizumab and trametinib (SBRT + K + M) or SBRT and gemcitabine (SBRT + G). Meanwhile, patients were classified into PD-L1+/tumor infiltrating lymphocytes [TIL(s)]- and PD-L1+/TIL + group for each arm. RESULTS: A total of 170 patients were enrolled and randomly assigned to receive SBRT + K + M (n = 85) or SBRT + G (n = 85). The improved outcomes have been reported in patients with SBRT + K + M in the previous study. In this secondary analysis, the median overall survival (OS) was 17.2 months (95% CI 14.6-19.8 months) in patients with PD-L1+/TIL + and 12.7 months (95% CI 10.8-14.6 months) in patients with PD-L1+/TIL- (HR 0.62, 95% CI 0.39-0.97, p = 0.036) receiving SBRT + K + M. In SBRT + G group, the median OS was 13.1 months (95% CI 10.9-15.3 months) in patients with PD-L1+/TIL- and 12.7 months (95% CI 9.2-16.2 months) in patients with PD-L1+/TIL+ (HR 0.97, 95% CI 0.62-1.52, p = 0.896). Grade 3 or 4 adverse events were found in 16 patients (30.8%) and 10 patients (30.3%) with PD-L1+/TIL- and PD-L1+/TIL + in SBRT + K + M group respectively; whereas 9 (16.7%) and 8 patients (25.8%) with PD-L1+/TIL- and PD-L1+/TIL + in SBRT + G group. CONCLUSION: PD-L1, TILs and mutant KRAS may be a biomarker to guide clinical practice of radiotherapy and immunotherapy-based regimens in pancreatic cancer if further combined with MEK inhibitors as targeted therapy.

Fully neuroendoscopic resection of cerebellopontine angle tumors through a retrosigmoid approach: a retrospective single-center study.

The objective of this study is to preliminarily investigate the surgical safety, efficacy, techniques, and clinical value of fully neuroendoscopic surgery for the resection of cerebellopontine angle (CPA) tumors via a retrosigmoid approach. The clinical data of 47 cerebellopontine angle area (CPA) tumors that were treated by full neuroendoscopic surgery from June 2014 to June 2023 were retrospectively analyzed. The efficacy and advantages of the surgical techniques were evaluated based on indicators such as duration of the surgery, neuroendoscopic techniques, intraoperative integrity of nerves and blood vessels, extent of tumor resection, outcomes or postoperative symptoms, and incidence of complications. The 47 cases of cerebellopontine angle tumors include 34 cases of epidermoid cysts, 7 cases of vestibular schwannomas, and 6 cases of meningiomas. All patients underwent fully neuroendoscopic surgery. Twenty tumors were removed using the one-surgeon two-hands technique, and 27 tumors were removed using the two-surgeons four-hands technique. The anatomical integrity of the affected cranial nerves was preserved in all 47 cases. None of the patients suffered a postoperative hemorrhage, cerebrospinal fluid leak, and aseptic or septic meningitis, or died. The rate of total tumor resection was 72.3% (34/47), and the symptom improvement rate was 89.4% (42/47). All patients were followed up for 2 to 12 months, and none died nor showed any signs of tumor recurrence. By analyzing 47 fully neuroendoscopic resections of CPA tumors using the posterior sigmoid sinus approach in our center, we believe that such method allows complete, safe, and effective resection of CPA tumors and is thereby worthy of clinical promotion.

Metabolic heterogeneity in different subtypes of malformations of cortical development causing epilepsy: a proton magnetic resonance spectroscopy study.

Background: The most common subtypes of malformations of cortical development (MCDs) are gray matter heterotopia (GMH), focal cortical dysplasia (FCD), and polymicrogyria (PMG). This study aimed to characterize the possible neurometabolic abnormalities and heterogeneity in different MCDs subtypes using proton magnetic resonance spectroscopy (1H-MRS). Methods: In this prospective cross-sectional study, we recruited 29 patients with MCDs and epilepsy, including ten with GMH, ten with FCD, and nine with PMG, as well as 25 age- and sex-matched healthy controls (HC) from the Epilepsy Center of West China Hospital of Sichuan University between August 2018 and November 2021. Inclusion criteria for the patients were based upon typical magnetic resonance imaging (MRI) findings of MCDs and full clinical assessment for epilepsy. Single-voxel point-resolved spectroscopy was used to acquire data from both the lesion and the normal-appearing contralateral side (NACS) in patients and from the frontal lobe in HC. Metabolite measures, including N-acetyl aspartate (NAA), myoinositol (Ins), choline (Cho), creatine (Cr), and glutamate + glutamine (Glx) concentrations, were quantitatively estimated with linear combination model (LCModel) software and corrected for the partial volume effect of cerebrospinal fluid (CSF). Results: The NAA concentration was lower and the Ins concentration was higher in the MCDs lesions than in the NACS and in HC (P=0.002-0.007), and the Cho and Cr concentrations were higher in MCDs lesions than in HC (P=0.001-0.016). Moreover, the Cho concentration was higher in NACS than in HC (P=0.015). In the GMH lesions, the only metabolic alteration was an NAA reduction (GMH_lesion vs. HC: P=0.001). In the FCD lesions, there were more metabolite abnormalities than in the other two subtypes, particularly a lower NAA and a higher Ins than in HC and NACS (P=0.012-0.042). In the PMG lesions, Cr (lesion vs. HC or NACS: P=0.017-0.021) and Glx (lesion vs. NACS: P=0.043) were increased, while NAA was normal. Correlation analysis revealed that the Cr concentration in MCDs lesions was positively correlated with seizure frequency (r=0.411; P=0.027). Conclusions: Based upon 1H-MRS, our study demonstrated that different MCDs subtypes exhibited variable metabolic features, which may be associated with distinct functional and cytoarchitectural properties.

Inhibition of FNDC1 suppresses gastric cancer progression by interfering with Gßγ-VEGFR2 complex formation.

Gastric cancer (GC) is a prevalent digestive tract malignant tumor characterized by an insidious onset, ease of metastasis, rapid growth, and poor prognosis. Here, we report that fibronectin type III domain containing 1 (FNDC1) has high expression in GC and indicates poor outcomes in patients with GC. FNDC1 over-expression or knockdown promotes or inhibits tumorigenesis and metastasis, respectively. The expression of FNDC1 is upregulated by TWIST1, strengthening its interaction with Gßγ and VEGFR2. The formation of the trimers, TWIST1 plus Gßγ and VEGFR2, increases VEGFR2 phosphorylation and Gßγ trafficking, which activates RAS-MAPK and PI3K-AKT signaling, benefiting GC progression. In this study, we demonstrated that arsenite can efficiently suppress FNDC1 expression, attenuating the formation of the trimers and downstream pathways. Altogether, our results indicate that FNDC1 might be a promising target for clinical treatment and prognostic judgment, while FNDC1 inhibition by arsenite provides a new opportunity for overcoming this fatal disease.

Evolutionary origin of genomic structural variations in domestic yaks.

Yak has been subject to natural selection, human domestication and interspecific introgression during its evolution. However, genetic variants favored by each of these processes have not been distinguished previously. We constructed a graph-genome for 47 genomes of 7 cross-fertile bovine species. This allowed detection of 57,432 high-resolution structural variants (SVs) within and across the species, which were genotyped in 386 individuals. We distinguished the evolutionary origins of diverse SVs in domestic yaks by phylogenetic analyses. We further identified 334 genes overlapping with SVs in domestic yaks that bore potential signals of selection from wild yaks, plus an additional 686 genes introgressed from cattle. Nearly 90% of the domestic yaks were introgressed by cattle. Introgression of an SV spanning the KIT gene triggered the breeding of white domestic yaks. We validated a significant association of the selected stratified SVs with gene expression, which contributes to phenotypic variations. Our results highlight that SVs of different origins contribute to the phenotypic diversity of domestic yaks.

USF2 activates RhoB/ROCK pathway by transcriptional inhibition of miR-206 to promote pyroptosis in septic cardiomyocytes.

Septic cardiomyopathy (SCM) is one of the most serious complications of sepsis. The present study investigated the role and mechanism of upstream stimulatory factor 2 (USF2) in SCM. Serum samples were extracted from SCM patients and healthy individuals. A murine model of sepsis was induced by caecal ligation and puncture (CLP) surgery. Myocardial injury was examined by echocardiography and HE staining. ELISA assay evaluated myocardial markers (CK-MB, cTnI) and inflammatory cytokines (TNF-α, IL-1ß, IL-18). Primary mouse cardiomyocytes were treated with lipopolysaccharide (LPS) to simulate sepsis in vitro. RT-qPCR and Western blot were used for analyzing gene and protein levels. CCK-8 assay assessed cell viability. NLRP3 was detected by immunofluorescence. ChIP, RIP and dual luciferase reporter assays were conducted to validate the molecular associations. USF2 was increased in serum from SCM patients, septic mice and primary cardiomyocytes. USF2 silencing improved the survival of septic mice and attenuated sepsis-induced myocardial pyroptosis and inflammation in vitro and in vivo. Mechanistically, USF2 could directly bind to the promoter of miR-206 to transcriptionally inhibit its expression. Moreover, RhoB was confirmed as a target of miR-206 and could promote ROCK activation and NLRP3 inflammasome formation. Moreover, overexpression of RhoB remarkably reversed the protection against LPS-induced inflammation and pyroptosis mediated by USF2 deletion or miR-206 overexpression in cardiomyocytes. The above findings elucidated that USF2 knockdown exerted a cardioprotective effect on sepsis by decreasing pyroptosis and inflammation via miR-206/RhoB/ROCK pathway, suggesting that USF2 may be a novel drug target in SCM.

Construction of engineered 3D islet micro-tissue using porcine decellularized ECM for the treatment of diabetes.

Islet transplantation improves diabetes patients' long-term blood glucose control, but its success and utility are limited by cadaver availability, quality, and considerable islet loss after transplantation due to ischemia and inadequate angiogenesis. This study used adipose, pancreatic, and liver tissue decellularized extracellular matrix (dECM) hydrogels in an effort to recapitulate the islet sites inside the pancreas in vitro, and successfully generated viable and functional heterocellular islet micro-tissues using islet cells, human umbilical vein endothelial cells, and adipose-derived mesenchymal stem cells. The three-dimensional (3D) islet micro-tissues maintained prolonged viability and normal secretory function, and showed high drug sensitivity in drug testing. Meanwhile, the 3D islet micro-tissues significantly enhanced survival and graft function in a mouse model of diabetes. These supportive 3D physiomimetic dECM hydrogels can be used not only for islet micro-tissue culture in vitro, but also have great promise for islet transplantation for the treatment of diabetes.

The FBXO32/ATR/ATM axis acts as a molecular switch to control the sensitivity of osteosarcoma cells to irradiation through its regulation of EXO1 expression.

Osteosarcoma (OS) is the most common primary bone cancer in children and adolescents. In clinical treatments, the insensitivity of OS to conventional radiotherapy regimens significantly contributes to poor patient prognosis and survival. EXO1 is responsible for DNA repair pathways and telomere maintenance. Meanwhile, ATM and ATR are considered switches because they can regulate the expression of EXO1. However, their expression and interaction in OS cells under irradiation (IR) remain unclear. This study aims to investigate the roles of FBXO32, ATM, ATR and EXO1 in OS radiotherapy insensitivity and poor patient prognosis and explore potential pathogenic mechanisms. Bioinformatics is employed to analyse differential gene expression and correlations with prognosis in OS. Cell counting kit 8 assay, clone formation assay, and flow cytometry are used to evaluate cell survival and apopotosis under IR. Co-IP assay is used to detect protein‒protein interactions. Bioinformatics analysis reveals that EXO1 is closely related to survival, apoptosis and poor prognosis in OS. Silencing of EXO1 suppresses cell proliferation and increases the sensitivity of OS cells. Molecular biological experiments show that ATM and ATR act as switches to regulate EXO1 expression under IR. Higher expression of EXO1, which is closely correlated with IR insensitivity and poorer prognosis, might be used as a prognostic indicator for OS. Phosphorylated ATM enhances the expression of EXO1, and phosphorylated ATR induces the degradation of EXO1. More importantly, FBXO32 degrades ATR via ubiquitination in a time-dependent manner. Our data may provide a reference for future research in the mechanisms, clinical diagnosis, and treatment of OS.

PI3K/ c-Myc/AFF4 axis promotes pancreatic tumorigenesis through fueling nucleotide metabolism.

MLL-AFF4 fusion gene has been discovered in acute leukemia, whether AFF4 alone plays a role in tumor, especially pancreatic tumorigenesis, is still elusive. Increasing evidence suggests that cancer cells altered nucleotide metabolism during tumorigenesis. In present study, we observed AFF4 overexpression promoted cell proliferation, colony formation and cell cycle progression while loss of AFF4 impairs above phenotypes of pancreatic ductal carcinoma (PDAC) cells. Using RNA-profiling, we revealed that HPRT1 and IMPDH2, two enzymes in the nucleotide metabolism pathway, were upregulated following AFF4 overexpression. Simultaneous expression of HPRT1 and IMPDH2 would mainly rescue the phenotypes of cells lacking AFF4. Additionally, xenograft study proved HPRT1 and IMPDH2 genetically function in the downstream of AFF4, which was recruited by PAX2 when CDK9 mediated AFF4 phosphorylation at S388 and drove HPRT1 and IMPDH2 expression. We further discovered PI3K/c-Myc axis is required for AFF4 expression in PDAC cells. Finally, we obtained the positive correlation between c-Myc and AFF4 or AFF4 and HPRT1/IMPDH2 in clinical PDAC samples. Otherwise, we conducted data-mining and found that the expression levels of AFF4 and HPRT1/IMPDH2 are correlated with patients' prognosis, establishing AFF4 as a potential biomarker and therapeutic target for PDAC.

Microencapsulation of tomato seed oil using phlorotannins-adducted pea protein isolate-chitosan and pea protein isolate-chitosan complex coacervates.

Pea protein isolates (PPI)/phlorotannins (PT)/chitosan (CS) ternary complex and PPI/CS binary complex were synthesized to prepare tomato seed oil (TSO) microcapsules. The concentration of PT was determined to be 0.025% (w/w) based on the solubility, emulsification, and UV-visible spectrum of PPI-PT complex. Subsequently, the optimal pHs associated with the formation of PPI/CS and PPI-PT/CS complex coacervates were determined to be pH 6.6 and 6.1, while the optimal ratios were 9:1 and 6:1, respectively. The coacervate microcapsules were successfully produced by freeze-dried method and those formulated with PPI-PT/CS displayed significantly lower surface oil content (14.57 ± 0.22%), higher encapsulation efficiency (70.54 ± 0.13%), lower particle size (5.97 ± 0.16 µm), and PDI (0.25 ± 0.02) than PPI/CS. The microcapsules were characterized by scanning electron microscopy and Fourier Transform infrared spectroscopy. Furthermore, the encapsulated TSO exhibited enhanced thermal and oxidative stability than that of free oil, along with microcapsules fabricated with PPI-PT/CS ternary complex showed better protection than that of free PT. Overall, PPI-PT/CS complex as an effective wall material in delivery system presented great potential.