Inhibition of STAT3 by S3I-201 suppress peritoneal fibroblast phenotype conversion and alleviate peritoneal fibrosis.

Peritoneal fibrosis is a common pathological response to long-term peritoneal dialysis (PD) and a major cause for PD discontinuation. Understanding the cellular and molecular mechanisms underlying the induction and progression of peritoneal fibrosis is of great interest. In our study, in vitro study revealed that signal transducer and activator of transcription 3 (STAT3) is a key factor in fibroblast activation and extracellular matrix (ECM) synthesis. Furthermore, STAT3 induced by IL-6 trans-signalling pathway mediate the fibroblasts of the peritoneal stroma contributed to peritoneal fibrosis. Inhibition of STAT3 exerts an antifibrotic effect by attenuating fibroblast activation and ECM production with an in vitro co-culture model. Moreover, STAT3 plays an important role in the peritoneal fibrosis in an animal model of peritoneal fibrosis developed in mice. Blocking STAT3 can reduce the peritoneal morphological changes induced by chlorhexidine gluconate. In conclusion, our findings suggested STAT3 signalling played an important role in peritoneal fibrosis. Therefore, blocking STAT3 might become a potential treatment strategy in peritoneal fibrosis.

Manipulating the Properties of Polymer Vitrimer Nanocomposites by Designing Dual Dynamic Covalent Bonds.

Polymer vitrimer is a novel material that contains dynamic covalent bonds (DCBs) allowing it to combine the desirable characteristics of both thermoplastics and thermosets. Similar to the traditional polymer nanocomposites, introducing nanoparticles into polymer vitrimer is also an effective strategy to further enhance its properties. However, a comprehensive understanding of matrix and interfacial bond exchange reactions (BERs) to tailor the properties of polymer vitrimer nanocomposites (PVNs) is still lacking. Herein, we utilized coarse-grained molecular dynamics simulations to investigate model PVNs in which there are two different kinds of DCBs in the vitrimer matrix and at the interface. Our results show that the normalized bond autocorrelation function (Csw) confirms the independence of BERs in the vitrimer matrix and in the interface. By varying the bond swap energy barrier (ΔEsw) in the matrix ΔEswmat or in the interface ΔEswint, or in both ΔEswall, a maximum mechanical property is observed at the moderate value of ΔEswmat, ΔEswint, orΔEswall. Meanwhile, the effect of ΔEsw on the stress relaxation and the bond orientation as a function of the time under a fixed strain is well probed, which both decay more slowly at greater ΔEsw. We simulated the tension-recovery curve to examine the effect of ΔEsw on the hysteresis loss and permanent deformation of PVNs, finding an optimal value to achieve its minimum energy dissipation and maximum recovery ratio. Lastly, we investigated the efficiency of self-healing by building and removing walls from the system. Interestingly, a maximum self-healing efficiency of the stress-strain behavior is observed at moderate ΔEsw. Overall, this study provides valuable insights into the relationship between the structure and properties of PVNs, offering implications for the manipulation of their mechanical properties and enhancement of their self-healing capabilities.

Precise Helium Sieving from Hydrogen Using Fluorine-Decorated Carbon Hollow Fiber Membranes.

Separating helium (He) and hydrogen (H2), two gases that are extremely similar in molecular size and condensation properties, presents a formidable challenge in the helium industry. The development of membranes capable of precisely differentiating between these gases is crucial for achieving large-scale, energy-efficient He/H2 separation. However, the limited selectivity of current membranes has hindered their practical application. In this study, we propose a novel approach to overcome this challenge by engineering submicroporous membranes through the fluorination of partially carbonized hollow fibers. We demonstrate that the fluorine substitution on the inner rim of the micropore walls within the carbon hollow fibers enables tunability of the microporous architecture. Furthermore, it enhances interactions between H2 molecules and the micropore walls through the polarization and hydrogen bonding induced by C-F bonds, resulting in simultaneous improvements in both He/H2 diffusivity and solubility selectivities. The fluorinated HFM-550-F-1 min membrane exhibits exceptional mixed-gas separation performance, with a binary mixed-gas He/H2 selectivity of 10.5 and a ternary mixed-gas He/(H2+CO2) selectivity of 20.8, at 40 bar feed pressure and 35 °C, surpassing all previously reported polymer-based gas separation membranes, and remarkable plasticization resistance and long-term continuous stability over 30 days.

Adaptive immune dysfunction in patients with COVID-19 and impaired kidney function during the omicron surge.

BACKGROUND: Little is known about the characteristics of lymphocyte subsets and the association with patient outcomes in COVID-19 with and without impaired kidney function. METHODS: Lymphocyte subsets were compared in COVID-19 patients with or without kidney dysfunction. The primary outcome was a composite of all-cause mortality or intensive care unit admission. Secondary outcomes included duration of viral shedding, length of hospital stay, and acute kidney injury. RESULTS: Lymphocyte subset cell counts demonstrated the lowest in patients with severe/critical COVID-19 and kidney dysfunction. Among all lymphocyte subset parameters, Th cell count was the most significant indicator for outcomes. ROC of the combined model of Th cell count and eGFR presented better predictive value than that of the other parameters. Th cell count <394.5 cells/µl and eGFR <87.5 ml/min/1·73m2 were independently associated with poor outcomes. The propensity score matching analysis revealed consistent results. CONCLUSIONS: Reduced Th cell count and eGFR may be applied as promising predictive indicators for identifying COVID-19 patients with high risk and poor outcomes.

Cancer Immunotherapy Based on Cell Membrane-Coated Nanocomposites Augmenting cGAS/STING Activation by Efferocytosis Blockade.

Innate immunity triggered by the cGAS/STING pathway has the potential to improve cancer immunotherapy. Previously, the authors reported that double-stranded DNA (dsDNA) released by dying tumor cells can trigger the cGAS/STING pathway. However, owing to efferocytosis, dying tumor cells are engulfed and cleared before the damaged dsDNA is released; hence, immunologic tolerance and immune escape occur. Herein, a cancer-cell-membrane biomimetic nanocomposites that exhibit tumor-immunotherapeutic effects are synthesized by augmenting the cGAS/STING pathway and suppressing efferocytosis. Once internalized by cancer cells, a combined chemo/chemodynamic therapy would be triggered, which damages their nuclear and mitochondrial DNA. Furthermore, the releasing Annexin A5 protein could inhibit efferocytosis effect and promote immunostimulatory secondary necrosis by preventing phosphatidylserine exposure, resulting in the burst release of dsDNA. These dsDNA fragments, as molecular patterns to immunogenic damage, escape from the cancer cells, activate the cGAS/STING pathway, enhance cross-presentation inside dendritic cells, and promote M1-polarization of tumor-associated macrophages. In vivo experiments suggest that the proposed nanocomposite could recruit cytotoxic T-cells and facilitate long-term immunological memory. Moreover, when combined with immune-checkpoint blockades, it could augment the immune response. Therefore, this novel biomimetic nanocomposite is a promising strategy for generating adaptive antitumor immune responses.

Anti-SARS-CoV-2 IgG levels in relation to disease severity of COVID-19.

The durability of infection-induced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunity has crucial implications for reinfection and vaccine effectiveness. However, the relationship between coronavirus disease 2019 (COVID-19) severity and long-term anti-SARS-CoV-2 immunoglobulin G (IgG) antibody level is poorly understood. Here, we measured the longevity of SARS-CoV-2-specific IgG antibodies in survivors who had recovered from COVID-19 1 year previously. In a cohort of 473 survivors with varying disease severity (asymptomatic, mild, moderate, or severe), we observed a positive correlation between virus-specific IgG antibody titers and COVID-19 severity. In particular, the highest virus-specific IgG antibody titers were observed in patients with severe COVID-19. By contrast, 74.4% of recovered asymptomatic carriers had negative anti-SARS-CoV-2 IgG test results, while many others had very low virus-specific IgG antibody titers. Our results demonstrate that SARS-CoV-2-specific IgG persistence and titer depend on COVID-19 severity.

A single-cell survey of the human glomerulonephritis.

Glomerulonephritis is the one of the major causes of the end-stage kidney disease, whereas the pathological process of glomerulonephritis is still not completely understood. Single-cell RNA sequencing (scRNA-seq) emerges to be a powerful tool to evaluate the full heterogeneity of kidney diseases. To reveal cellular gene expression profiles of glomerulonephritis, we performed scRNA-seq of 2 human kidney transplantation donor samples, 4 human glomerulonephritis samples, 1 human malignant hypertension (MH) sample and 1 human chronic interstitial nephritis (CIN) sample, all tissues were taken from the biopsy. After filtering the cells with < 200 genes and > 10% mitochondria (MT) genes, the resulting 14 932 cells can be divided into 20 cell clusters, consistently with the previous report, in disease samples dramatic immune cells infiltration was found, among which a proximal tubule (PT) subset characterized by wnt-ß catenin activation and a natural killer T (NKT) subset high expressing LTB were found. Furthermore, in the cluster of the podocyte, three glomerulonephritis related genes named FXYD5, CD74 and B2M were found. Compared with the mesangial of donor, the gene CLIC1 and RPS26 were up-regulated in mesangial of IgA nephropathy(IgAN), whereas the gene JUNB was up-regulated in podocyte of IgAN in comparison with that of donor. Meanwhile, some membranous nephropathy (MN) high expressed genes such as HLA-DRB5, HLA-DQA2, IFNG, CCL2 and NR4A2, which involve in highest enrichment pathway, display the cellular-specific expression style, whereas monocyte marker of lupus nephritis (LN) named TNFSF13B was also found and interferon alpha/beta signalling pathway was enriched in B and NKT of LN comparing with donor. By scRNA-seq, we first defined the podocyte markers of glomerulonephritis and specific markers in IgA, MN and LN were found at cellular level. Furthermore, the critical role of interferon alpha/beta signalling pathway was enriched in B and NKT of LN was declared.

Associations between dialysate interleukin-6 and Tie-2 and peritoneal solute transport rate and outcomes for patients undergoing peritoneal dialysis: A prospective cohort study.

OBJECTIVES: We designed this prospective observational study to clarify the associations between dialysate IL-6, a marker of ongoing peritoneal inflammation, Tie2, an important factor in angiogenesis in the peritoneum, and a high peritoneal solute transport rate (PSTR) in patients undergoing peritoneal dialysis (PD) and to investigate their outcome predictive roles. METHODS: A total of 60 stable continuous ambulatory peritoneal dialysis (CAPD) patients from a single center in China were analyzed in this prospective study. We measured dialysate levels of IL-6 and Tie-2 using ELISAs. Our primary study endpoint was all-cause mortality with 10 years' follow-up. RESULTS: For the evaluation of PSTR, we used the Dialysis/Plasma creatinine (D/Pcr) ratio. We subdivided the patients into two groups for statistical evaluation: low and low average D/Pcr (<0.64; L/A), and high and high average D/Pcr (≥0.65; H/A) transporters. The mean levels of dialysates IL-6 (21.71 ± 8.88 pg/mL) and Tie-2 (1.23 ± 0.43 ng/mL) were significantly higher in the H/A (high and high average, group than those in the L/A group (13.94 ± 5.43 pg/mL, p<0.001 and 0.95 ± 0.43 ng/mL, p=0.019; respectively). Moreover, IL-6 and Tie-2 were positively correlated with D/Pcr (r=0.366, p=0.004 and r=0.402, p=0.001; respectively). Both dialysates IL-6 and Tie-2 were independent determinants of a high peritoneal solute transport rate. After follow-up for 42.65±18.08 months, 30 patients (50.0%) had died. An increased D/Pcr increased the risk of all-cause mortality in patients with CAPD (p=0.018), but the dialysates IL-6 and Tie2 were not independent predictors of all-cause mortality (p>0.05). CONCLUSION: Our results suggest that patients undergoing CAPD have a high peritoneal solute transport status with local peritoneal inflammation and angiogenesis. Increased D/Pcr is a relative risk factor for mortality and technique failure in patients undergoing CAPD.

Pharmacological inhibition of heparin-binding EGF-like growth factor promotes peritoneal angiogenesis in a peritoneal dialysis rat model.

BACKGROUND: Molecular mechanisms of peritoneal dialysis (PD) ultrafiltration failure, peritoneal neo-angiogenesis, and fibrosis remain to be determined. We aimed to determine the role of heparin-binding EGF-like growth factor (HB-EGF) inhibition on angiogenesis of peritoneal membrane in a PD rat model. METHODS: 32 male Wistar rats were assigned into (1) control group; (2) uremic non-PD group: subtotal nephrectomy-induced uremic rats without PD; (3) uremic rats subjected to PD: uremic rats that were dialyzed with Dianeal® for 4 weeks; (4) CRM 197 group: dialyzed uremic rats were supplemented with CRM197, a specific HB-EGF inhibitor. Peritoneal transport function was examined by peritoneal equilibration test. Expression of HB-EGF and EGFR in peritoneal samples were examined by real-time PCR, immunohistochemical staining, and western blot. RESULTS: Progressive angiogenesis and fibrosis were observed in uremic PD rats, and there were associated with decreased net ultrafiltration (nUF), increased permeability of peritoneal membrane, and reduced expression of HB-EGF and EGFR protein and mRNA in uremic PD rats compared to uremic non-PD or control groups (both p < 0.05). CRM197 significantly induced peritoneal membrane permeability, decreased nUF, increased higher vessel density, and reduced pericyte count compared to that of uremic PD rats. The levels of HB-EGF and EGFR expression negatively correlated with vessel density in peritoneal membrane (both p < 0.001). CONCLUSION: PD therapy was associated with peritoneal angiogenesis, functional deterioration, and downregulation of HB-EGF/EGFR. Pharmacological inhibition of HB-EGF promoted PD-induced peritoneal angiogenesis and fibrosis and ultrafiltration decline, suggesting that HB-EGF downregulation contributes to peritoneal functional deterioration in the uremic PD rat model.

Study on age-dependent pre-existing 2009 pandemic influenza virus T and B cell responses from Chinese population.

BACKGROUND: The outbreak of the 2009 H1N1 influenza pandemic (H1N1pdm) affected thousands of people in Mexico and the United States, and spread rapidly throughout the world from April 2009 to July 2010. To explore the age-specific prevalence of seroprotection against H1N1pdm infection, we estimated pre-existing humoral and cellular immunities of residents in Northern China against H1N1pdm and seasonal H1N1 virus in an age-dependent manner. METHODS: Anonymous serum samples were collected from 1425 to 1434 adult healthy individuals before and after the pandemic outbreak, and then grouped by birth year 1913-1990. The antibody titers of H1N1pdm and seasonal H1N1 were determined using microneutralization (MN) assays, and the proportion of seropositive was estimated based on the year of birth. Separately, another 63 blood samples were collected in 2006 and prepared for analysis of virus specific memory B and IFN-γ+ T cells using the ELISpot assays. RESULTS: The prevalence of pre-existing H1N1pdm-specific sero-antibodies in the elderly population (>60 years old) was 7.8%. The younger group, aged 19 to 60 years, exhibited a significant increase in seropositivity for H1N1pdm after the pandemic (4.9% before pandemic and 18.9% after pandemic, p < 0.05). The prevalence of H1N1pdm specific MBCs before the pandemic in the elderly (>60 years) and younger populations (<60 years) was 38% (8/21) and 48% (20/42), respectively (p = 0.6). The IFN-γ+ T cell responses to the pandemic and seasonal viruses were significantly lower in the elder group than those in the younger group (<60 years) (p < 0.05). CONCLUSIONS: Pre-existing serum antibodies and memory B cells against H1N1pdm were low in all age group, whereas diminished memory T cell responses to this virus were observed in the elderly population both before and after the pandemic.

Protopanaxadiol prevents cisplatin-induced acute kidney injury by regulating ferroptosis.

OBJECTIVES: Acute kidney injury (AKI) caused by cisplatin (CDDP) is a complex, critical illness with no effective or specific treatment. The purpose of the study was to assess the protective effect of protopanaxadiol (PPD) on the kidneys in CDDP-induced AKI models and its possible mechanisms. METHODS: In vitro, the protection of PPD was assessed in HK-2. KM mice were injected with CDDP to induce AKI models in vivo. The determination of blood urea nitrogen and serum creatinine (SCr) was performed, and pathological changes were examined by histopathological examination. Immunostaining and western blot analyses were used to analyze the expression levels of proteins. RESULTS: PPD can increase the viability of HK-2 cells damaged by CDDP, improve cell morphology, and alleviate the symptoms of AKI in mice. In addition, PPD can down-regulate the protein expression of TRF and up-regulate the protein expression of Ferritin heavy chain, Glutathione peroxidase 4, and ferroptosis suppressor protein 1 reduce the iron content in cells and kidney tissues, and restore the antioxidant defense system. CONCLUSION: PPD has an inhibitory effect on cisplatin-induced nephrotoxicity, which may be related to the inhibition of ferroptosis by regulating iron metabolism and lipid peroxidation.

Assessment of Peanut Protein Powder Quality by Near-Infrared Spectroscopy and Generalized Regression Neural Network-Based Approach.

The global demand for protein is on an upward trajectory, and peanut protein powder has emerged as a significant player, owing to its affordability and high quality, with great future market potential. However, the industry currently lacks efficient methods for rapid quality testing. This research paper addressed this gap by introducing a portable device with employed near-infrared spectroscopy (NIR) to quickly assess the quality of peanut protein powder. The principal component analysis (PCA), partial least squares (PLS), and generalized regression neural network (GRNN) methods were used to construct the model to further enhance the accuracy and efficiency of the device. The results demonstrated that the newly established NIR method with PLS and GRNN analysis simultaneously predicted the fat, protein, and moisture of peanut protein powder. The GRNN model showed better predictive performance than the PLS model, the correlation coefficient in calibration (Rcal) of the fat, the protein, and the moisture of peanut protein powder were 0.995, 0.990, and 0.990, respectively, and the residual prediction deviation (RPD) were 10.82, 10.03, and 8.41, respectively. The findings unveiled that the portable NIR spectroscopic equipment combined with the GRNN method achieved rapid quantitative analysis of peanut protein powder. This advancement holds a significant application of this device for the industry, potentially revolutionizing quality testing procedures and ensuring the consistent delivery of high-quality products to fulfil consumer desires.

The effect of physical exercise therapy on autism spectrum disorder:a systematic review and meta-analysis.

BACKGROUND: Physical Exercise Therapy (PET) is increasingly applied in the treatment of Autism Spectrum Disorders (ASD), yet the empirical evidence supporting its efficacy remains ambiguous. This systematic review and meta-analysis aimed to investigate the effectiveness of PET for individuals with ASD, providing evidence-based support for clinical and scientific research. METHODS: We systematically searched four international databases (Medline via PubMed, Embase, Cochrane Libraries, and Web of Science) and three Chinese databases (CNKI, Wanfang, and VIP Libraries) up to July 31, 2023. The search was conducted in both English and Chinese for original research articles employing randomized-controlled-trial (RCT) designs to study PET's effects on individuals diagnosed with ASD according to DSM or other established criteria. Co-primary outcomes focused on the overall severity of autism, while secondary outcomes included measures of stereotyped behaviors, social deficits, social skills, and executive functioning. Data from the included studies were synthesized and analyzed using RevMan 5.4. This systematic review is registered with PROSPERO (CRD42023443951). RESULTS: A total of 28 RCTs comprising 1081 participants were analyzed. Of these, only three studies met high-quality standards. Compared to control groups, PET showed improvement in at least one core symptom of autism, including Motor Performance (SMD=1.72, 95%CI[1.01, 2.44], I2=90%), Restricted Repetitive Behaviors (SMD=-0.81, 95%CI[-1.00, -0.62], I2=0%), Social Dysfunction (SMD=-0.76, 95%CI[-1.06, -0.46], I2=47%). CONCLUSIONS: PET may offer benefits in reducing the overall severity and associated symptoms in individuals with ASD. However, given the high overall risk of bias in the included studies, these findings should be interpreted with caution.

[Research progress on risk prediction of cardiac arrest].

Cardiac arrest (CA) is a serious cardiac event, which has a high incidence and low survival rate at home and abroad. In order to predict the risk of CA in advance, a large number of studies have been conducted by relevant researchers. This paper mainly summarizes the characteristics and research status of the existing analysis and prediction of CA from three aspects: the risk prediction factors of CA, the evaluation index of risk prediction of CA and the early warning scoring system of CA. We hope it can help medical staff to understand the current progress in this field, and provide new ways and methods for predicting the risk of CA.

FPR3 reprograms glycolytic metabolism and stemness in gastric cancer via calcium-NFATc1 pathway.

Aerobic glycolysis accelerates tumor proliferation and progression, and inhibitors or drugs targeting abnormal cancer metabolism have been developing. Cancer stem-like cells (CSCs) significantly contribute to tumor initiation, metastasis, therapy resistance, and recurrence. Formyl peptide receptor 3 (FPR3), a member of FPR family, involves in inflammation, tissue repair, and angiogenesis. However, studies in exploring the regulatory mechanisms of aerobic glycolysis and CSCs by FPR3 in gastric cancer (GC) remain unknown. Here, we demonstrated that overexpressed FPR3 suppressed glycolytic capacity and stemness of tumor cells, then inhibited GC cells proliferation. Mechanistically, FPR3 impeded cytoplasmic calcium ion flux and hindered nuclear factor of activated T cells 1 (NFATc1) nuclear translocation, leading to the transcriptional inactivation of NFATc1-binding neurogenic locus notch homolog protein 3 (NOTCH3) promoter, subsequently obstructing NOTCH3 expression and the AKT/mTORC1 signaling pathway, and ultimately downregulating glycolysis. Additionally, NFATc1 directly binds to the sex determining region Y-box 2 (SOX2) promoter and modifies stemness in GC. In conclusion, our work illustrated that FPR3 played a negative role in GC progression by modulating NFATc1-mediated glycolysis and stemness in a calcium-dependent manner, providing potential insights into cancer therapy.

Anti-adipogenesis and anti-obesity potential of alliin mediated by modulating glycolipid metabolism via activating PPARγ signaling.

Garlic exhibits hypolipidemic, hypoglycemic, and cardiovascular benefits. The inconsistent results of garlic preparations on adipogenesis have caused more confusion in the public and academia. The compounds responsible for the anti-adipogenesis effect of garlic remain unknown. The present study aimed to verify the real anti-adipogenesis and anti-obesity component in garlic and explored its possible effects in metabolic syndrome. We verified the real anti-adipogenesis and anti-obesity components of garlic in 3T3-L1 preadipocytes and a 10-week-high fat diet (HFD)-induced obese mice. In vitro, two water-soluble and four typical lipid-soluble compounds of garlic were tested for their anti-adipogenesis. Then, the water-soluble compound, alliin, and two processing methods produced garlic oils, were evaluated in vivo study. Mice received oral administration of alliin (25 mg/kg) and garlic oils (15 mg/kg) daily for 8 weeks. Serum lipids, parameters of obesity, and indicators involved in regulating glycolipid metabolism were examined. Our findings confirmed that both water-soluble and lipid-soluble organosulfur compounds of garlic contributed to garlic's anti-adipogenesis effect, in which water-soluble sulfides, especially alliin, exhibited greater potency. Alliin possessed potent effects of anti-obesity and improvement in glucose and lipid metabolism in HFD-induced obese mice. Alliin mediated these effects partly attributed to its modulation of enzymatic activities within glycolipid metabolism and activating PPARγ signaling pathway. In contrast to odorous lipid-soluble sulfides, alliin is odorless, stable, and safe, and is an ideal nutraceutical or even medicinal candidates for the treatment of metabolic diseases. Alliin could be used to standardize the quality of garlic products.

Protopanaxadiol improves lupus nephritis by regulating the PTX3/MAPK/ERK1/2 pathway.

Lupus nephritis (LN) is a kidney disease that occurs after systemic lupus erythematosus (SLE) affects the kidneys. Pentraxin 3 (PTX3) is highly expressed in the serum of patients with LN. Renal PTX3 deposition is directly related to clinical symptoms such as proteinuria and inflammation. The excessive proliferation of mesangial cells (MCs) is one of the representative pathological changes in the progression of LN, which is closely related to its pathogenesis. Protopanaxadiol (PPD) is the main component of ginsenoside metabolism and has not been reported in LN. The aim of this study was to investigate the relationship between PTX3 and mesangial cell proliferation and to evaluate the potential role and mechanism of PPD in improving LN. PTX3 is highly expressed in the kidneys of LN patients and LN mice and is positively correlated with renal pathological indicators, including proteinuria and PCNA. The excessive expression of PTX3 facilitated the proliferation of MCs, facilitated the activation of the MAPK/ERK1/2 signaling pathway, and increased the expression of HIF-1α. Further studies showed that PPD can effectively inhibit the abnormal proliferation of MCs with high expression of PTX3 and significantly improve LN symptoms such as proteinuria in MRL/lpr mice. The mechanism may be related to the inhibition of the PTX3/MAPK/ERK1/2 pathway. In this study, both in vitro, in vivo, and clinical sample results show that PTX3 is involved in the regulation of MCs proliferation and the early occurrence of LN. Natural active compound PPD can improve LN by regulating the PTX3/MAPK/ERK1/2 pathway.

Minor protopanaxadiol type sapogenins from the alkali hydrolysate of stems-leaves of Panax notoginseng.

Two new protopanaxadiol type sapogenins, (3ß,12ß)-3,12,20-trihydroxydammar-24-en-26-al (1) and (3ß,12ß)-3,12,20-trihydroxydammar-24-en-26-oic acid (2), were isolated from the alkali hydrolysate of stems-leaves of Panax notoginseng, along with seven known analogues (3-9). Their structures were elucidated by spectroscopic analyses and single-crystal X-ray diffraction. Compound 2 and the known sapogenins 5-8 displayed weak to moderate inhibition of NO production in LPS-induced RAW264.7 macrophages with IC50 values from 44.5 to 143.6 µM, respectively.

Properties and Characterization of Sunflower Seeds from Different Varieties of Edible and Oil Sunflower Seeds.

Sunflower seeds, oil, and protein powder are rich in nutritional value, but the quality of different varieties of sunflower seeds is quite different, and the comprehensive comparative analysis characteristics of edible and oil sunflower seeds are still unclear. The comprehensive analysis and comparison of the raw material indicators, physicochemical properties, and processing characteristics of four edible and four oil sunflower seed varieties were investigated. The results showed that the engineering properties, texture characteristics, single-cell structure, and oil, protein, and starch granule distribution were different between edible and oil sunflower seeds. The composition of fatty acids and amino acids was different among edible, oil sunflower seeds and different varieties. The oleic acid (18.72~79.30%) and linoleic acid (10.11~51.72%) were the main fatty acids in sunflower seed oil, and in amino acid composition, the highest content was glutamic acid (8.88~11.86 g/100 g), followed by aspartic acid (3.92~4.86 g/100 g) and arginine (4.03~4.80 g/100 g). Sunflower meal proteins were dominated by 11S globulin and 2S albumin, and the secondary structure was dominated by ß-folding, with -SH and S-S varying greatly among different varieties. Sunflower meal proteins vary widely in terms of functional properties among different varieties, and specialized quality screening was necessary. This study provided a reference and theoretical support for understanding sunflower seeds to further promote the processing and utilization of sunflower seeds.

SCD1 promotes the stemness of gastric cancer stem cells by inhibiting ferroptosis through the SQLE/cholesterol/mTOR signalling pathway.

Cancer stem cells (CSCs) play a substantial role in cancer onset and recurrence. Anomalous iron and lipid metabolism have been documented in CSCs, suggesting that ferroptosis, a recently discovered form of regulated cell death characterised by lipid peroxidation, could potentially exert a significant influence on CSCs. However, the precise role of ferroptosis in gastric cancer stem cells (GCSCs) remains unknown. To address this gap, we screened ferroptosis-related genes in GCSCs using The Cancer Genome Atlas and corroborated our findings through quantitative polymerase chain reaction and western blotting. These results indicate that stearoyl-CoA desaturase (SCD1) is a key player in the regulation of ferroptosis in GCSCs. This study provides evidence that SCD1 positively regulates the transcription of squalene epoxidase (SQLE) by eliminating transcriptional inhibition of P53. This mechanism increases the cholesterol content and the elevated cholesterol regulated by SCD1 inhibits ferroptosis via the mTOR signalling pathway. Furthermore, our in vivo studies showed that SCD1 knockdown or regulation of cholesterol intake affects the stemness of GCSCs and their sensitivity to ferroptosis inducers. Thus, targeting the SCD1/squalene epoxidase/cholesterol signalling axis in conjunction with ferroptosis inducers may represent a promising therapeutic approach for the treatment of gastric cancer based on GCSCs.