Dual role of targeting NAE1 in nasopharyngeal carcinoma: Antitumor effects yet inducing radiotherapy resistance.

Background and objectives: The inhibitor MLN4924 of Neural Precursor Cell-Expressed Developmentally Down-Regulated 8 (NEDD8) Activating Enzyme 1 (NAE1) has been found to suppress the growth of nasopharyngeal carcinoma (NPC). However, its effect on NPC's radiotherapy sensitivity remains unclear. Methods: By integrating single-cell RNA sequencing and bulk RNA sequencing, we predict the impact of NAE1 on the cell cycle, cell death, and its relationship with radiotherapy sensitivity and prognosis in NPC. The effect of inhibiting NAE1 on NPC cell behavior and radiation sensitivity is explored through MLN4924 intervention in vitro and in vivo. We construct a prognosis prediction model based on NAE1 using machine learning methods and validate the efficacy of NAE1 and the model in clinical cohorts. Results: NPC patients with high NAE1 expression have better prognosis and higher expression in the radiotherapy-sensitive group. Inhibiting NAE1 with MLN4924 causes cell cycle arrest in NPC cells, preventing them from entering the G2/M phase, thereby inhibiting proliferation but not affecting migration and metastasis. However, in vitro and in vivo experiments demonstrate that inhibiting NAE1 with MLN4924 leads to increased resistance of NPC to radiation. Conclusions: Targeting NAE1 for NPC treatment may have dual effects, inhibiting NPC proliferation while also increasing radiation resistance.

Defect Engineering of Ultrasmall TiO2 Nanoparticles Enables Highly Efficient Photocatalysts for Solar H2 Production from Woody Biomass.

The conversion of woody biomass to H2 through photocatalysis provides a sustainable strategy to generate renewable hydrogen fuel but was limited by the slow decomposition rate of woody biomass. Here, we fabricate ultrasmall TiO2 nanoparticles with tunable concentration of oxygen vacancy defects (VO-TiO2) as highly efficient photocatalysts for photocatalytic conversion of woody biomass to H2. Owing to the positive role of oxygen vacancy in reducing energy barrier for the generation of •OH which was the critical species to oxidize woody biomass, the obtained VO-TiO2 achieves rapid photocatalytic conversion of α-cellulose and poplar wood chip to H2 in the presence of Pt nanoclusters as the cocatalyst. As expected, the highest H2 generation rate in α-cellulose and poplar wood chip system respectively achieve 1146 and 59 µmol h-1 g-1, and an apparent quantum yield of 4.89% at 380 nm was obtained in α-cellulose aqueous solution.

Photoredox/NHC Dual Catalysis Enabled de Novo Synthesis of α-Amino Acids Derivatives.

Herein, we report a mild and operationally simple photoredox/NHC dual catalysis strategy for the α-carboxylation of tertiary amine C(sp3)-H bonds using diethyl pyrocarbonate. This method offers a novel approach for synthesizing α-amino acid derivatives. The protocol features a broad substrate scope, accommodating both N-aryl tetrahydroisoquinolines (THIQ) and N-methyl aniline and is scalable to gram quantities. Additionally, it is suitable for the late-stage derivatization of certain pharmaceutical compounds.

Radical-polar crossover reaction of glycine derivatives.

Here we report a visible-light facilitated radical addition strategy for the preparation of various natural or unnatural α-amino acids from readily available glycine derivatives and alkenes. A key aspect in achieving this side carbon chain introduction reaction, while circumventing the well-documented cyclization pathway, was the employment of a radical-polar crossover strategy under redox neutral conditions.

Association between sleep and periodontitis: NHANES 2009-2014 and Mendelian randomization study.

OBJECTIVE: We assessed association between periodontitis and sleep patterns. METHODS: Our study included 7289 participants based on a large-scale study in NHANES. Periodontitis was defined through an oral examination. We used logistic regression to explore association between sleep status and risk of periodontitis. Further, stratified analysis was conducted. We performed a Mendelian randomization (MR) analysis using publicly available genetic data from corresponding studies. RESULTS: Odds Ratio (OR) of periodontitis was 1.25 (1.07-1.46) in individuals with < 7 hours/per night. Stratification analysis showed individuals under 45 years old (OR: 1.28, 95% CI: 1.07-1.54), women (1.28(1.07-1.54)), education levels below high school (1.45(1.03-2.05)) and higher family income (-1.28(1.06-1.56)) were more likely to deteriorate to periodontitis if sleep time less than 7 hours. IVW-MR showed periodontitis risk was not associated with genetically increased levels of sleep time (0.22 (0.02-3.05)) or insomnia (0.83(0.55-1.24)). CONCLUSION: There was no indication that sleep status was associated with periodontitis.

Unraveling the impact of irritability on esophageal diseases: Insights from multivariable Mendelian randomization analysis.

BACKGROUND: Previous studies have suggested a potential association between irritability and the risk of various diseases. However, establishing a causal relationship has remained a significant challenge. To address this issue, we employed Mendelian randomization (MR), a sophisticated approach that leverages genotype data to emulate the conditions of randomized controlled trials. This method enables us to investigate the potential causal link between irritability and the susceptibility to esophageal diseases. METHODS: We conducted an extensive multivariable MR analysis using summary-level data from genome-wide association studies (GWAS) encompassing various esophageal diseases, including gastroesophageal reflux disease (GERD), esophageal cancer (EC), and Barrett's esophagus. Both univariable and multivariable MR analyses were performed to elucidate and confirm the causal association between genetically predicted irritability and the incidence of esophageal diseases. RESULTS: Based on our primary causal effects model utilizing MR analyses with the inverse-variance weighted (IVW) method, genetically predicted irritability was identified as a risk factor for GERD (OR = 2.413; 95 % CI: 1.678-3.470; P = 2.03E-06) and Barrett's esophagus (OR = 2.306; 95 % CI: 1.042-5.101; P = 0.039). However, irritability was not found to be associated with the risk of EC, even after adjusting for BMI, smoking initiation, and alcohol consumption. CONCLUSION: The multivariable MR analysis performed in this study demonstrated a causal relationship between irritability and esophageal diseases. It is imperative to acknowledge the need for further large-scale prospective studies to validate these findings.

Confining platinum clusters in indium-modified ZSM-5 zeolite to promote propane dehydrogenation.

Designing highly active and stable catalytic sites is often challenging due to the complex synthesis procedure and the agglomeration of active sites during high-temperature reactions. Here, we report a facile two-step method to synthesize Pt clusters confined by In-modified ZSM-5 zeolite. In-situ characterization confirms that In is located at the extra-framework position of ZSM-5 as In+, and the Pt clusters are stabilized by the In-ZSM-5 zeolite. The resulting Pt clusters confined in In-ZSM-5 show excellent propane conversion, propylene selectivity, and catalytic stability, outperforming monometallic Pt, In, and bimetallic PtIn alloys. The incorporation of In+ in ZSM-5 neutralizes Brønsted acid sites to inhibit side reactions, as well as tunes the electronic properties of Pt clusters to facilitate propane activation and propylene desorption. The strategy of combining precious metal clusters with metal cation-exchanged zeolites opens the avenue to develop stable heterogeneous catalysts for other reaction systems.

Treatment-Switching Adjustment of Overall Survival in CheckMate 227 Part 1 Evaluating First-Line Nivolumab Plus Ipilimumab Versus Chemotherapy for Metastatic Nonsmall Cell Lung Cancer.

OBJECTIVES: CheckMate 227 (NCT02477826) evaluated first-line nivolumab-plus-ipilimumab versus chemotherapy in patients with metastatic nonsmall cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1) expression ≥ 1% or < 1% and no EGFR/ALK alterations. However, many patients randomized to chemotherapy received subsequent immunotherapy. Here, overall survival (OS) and relative OS benefit of nivolumab-plus-ipilimumab were adjusted for potential bias introduced by treatment switching. MATERIALS AND METHODS: Treatment-switching adjustment analyses were conducted following the NICE Decision Support Unit Technical Support Document 16, for CheckMate 227 Part 1 OS data from treated patients (database lock, July 2, 2019). Inverse probability of censoring weighting (IPCW) was used in the base-case analysis; other methods were explored as sensitivity analyses. RESULTS: Of 1166 randomized patients, 391 (PD-L1 ≥ 1%) and 185 (PD-L1 < 1%) patients received nivolumab-plus-ipilimumab; 387 (PD-L1 ≥ 1%) and 183 (PD-L1 < 1%) patients received chemotherapy, with 29.3-month minimum follow-up. Among chemotherapy-treated patients, 169/387 (43.7%; PD-L1 ≥ 1%) and 66/183 (36.1%; PD-L1 < 1%) switched to immunotherapy poststudy. Among treated patients, median OS was 17.4 months with nivolumab-plus-ipilimumab versus 14.9 months with chemotherapy (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.68-0.95) in the PD-L1 ≥ 1% subgroup and 17.1 versus 12.4 months (HR, 0.62; 95% CI, 0.49-0.80) in the PD-L1 < 1% subgroup. After treatment-switching adjustment using IPCW, the HR (95% CI) for OS for nivolumab-plus-ipilimumab versus chemotherapy was reduced to 0.68 (0.56-0.83; PD-L1 ≥ 1%) and 0.53 (0.40-0.69; PD-L1 < 1%). Sensitivity analyses supported the robustness of the results. CONCLUSION: Treatment-switching adjustments resulted in a greater estimated relative OS benefit with first-line nivolumab-plus-ipilimumab versus chemotherapy in patients with metastatic NSCLC.

The prognostic value of controlling nutritional status score on esophageal squamous cell carcinoma patients with neoadjuvant therapy followed by esophagectomy-a retrospective research.

Background: A variety of nutritional evaluation parameters has been documented as prognostic indicators in some malignancies. However, the prognostic significance of the controlling nutritional status (CONUT) score, as one of these nutritional indices, in patients with esophageal squamous cell carcinoma (ESCC) remains unclear and warrants investigation. Our study sought to elucidate the prognostic value of this nutritional index in ESCC patients who underwent neoadjuvant therapy followed by esophagectomy. Methods: This retrospective study encompassed 314 patients diagnosed with ESCC who underwent neoadjuvant therapy followed by esophagectomy at West China Hospital of Sichuan University between August 2016 and August 2021. CONUT scores were computed at two specific time points: prior to neoadjuvant therapy initiation and before surgery, utilizing serum albumin, total lymphocyte, and cholesterol levels of ESCC patients. Furthermore, the delta CONUT (ΔCONUT) score was derived by subtracting the preoperative CONUT score from the pretreatment CONUT score. The associations between CONUT scores and various survival outcomes were evaluated using Kaplan-Meier methods and Cox regression analysis. Results: Patients with a high preoperative CONUT score demonstrated a higher postoperative complication rate [odds ratio (OR) =2.009, 95% confidence interval (CI): 1.150-3.510, P=0.01] compared to those in the low CONUT group. Multivariate analysis revealed that a ΔCONUT score ≥0 served as an independent negative prognostic indicator for increased postoperative complications (OR =3.008, 95% CI: 1.509-5.999, P=0.002) and poorer overall survival [hazard ratio (HR) =2.388, 95% CI: 1.052-5.422, P=0.04] in ESCC patients who underwent neoadjuvant therapy combined with esophagectomy. Conclusions: A high preoperative CONUT score and a ΔCONUT score ≥0 were indicative of a poor prognostic nutritional status in ESCC patients who had undergone neoadjuvant therapy followed by esophagectomy.

Clinical efficacy and immune response of neoadjuvant camrelizumab plus chemotherapy in resectable locally advanced oesophageal squamous cell carcinoma: a phase 2 trial.

BACKGROUND: Neoadjuvant immunotherapy is under intensive investigation for esophageal squamous cell carcinoma (ESCC). This study assesses the efficacy and immune response of neoadjuvant immunochemotherapy (nICT) in ESCC. METHODS: In this phase II trial (ChiCTR2100045722), locally advanced ESCC patients receiving nICT were enrolled. The primary endpoint was the pathological complete response (pCR) rate. Multiplexed immunofluorescence, RNA-seq and TCR-seq were conducted to explore the immune response underlying nICT. RESULTS: Totally 42 patients were enrolled, achieving a 27.0% pCR rate. The 1-year, 2-year DFS and OS rates were 89.2%, 64.4% and 97.3%, 89.2%, respectively. RNA-seq analysis highlighted T-cell activation as the most significantly enriched pathway. The tumour immune microenvironment (TIME) was characterised by high CD4, CD8, Foxp3, and PD-L1 levels, associating with better pathological regression (TRS0/1). TIME was categorised into immune-infiltrating, immune-tolerant, and immune-desert types. Notably, the immune-infiltrating type and tertiary lymphoid structures correlated with improved outcomes. In the context of nICT, TIM-3 negatively influenced treatment efficacy, while elevated TIGIT/PD-1 expression post-nICT correlated positively with CD8+ T cell levels. TCR-seq identified three TCR rearrangements, underscoring the specificity of T-cell responses. CONCLUSIONS: Neoadjuvant camrelizumab plus chemotherapy is effective for locally advanced, resectable ESCC, eliciting profound immune response that closely associated with clinical outcomes.

[Changes and significance of oxidized phospholipids and endothelial nitric oxide synthase in the acute stage of Kawasaki disease]. / å·å´Žç— æ€¥æ€§æœŸæ°§åŒ–ç£·è„‚å’Œå† çš®ä¸€æ°§åŒ–æ°®åˆé ¶çš„å˜åŒ–åŠæ„ä¹‰.

OBJECTIVES: To investigate the changes in the serum levels of oxidized phospholipids (OxPLs) and endothelial nitric oxide synthase (eNOS) and their association with coronary artery disease (CAL) in children in the acute stage of Kawasaki disease (KD), as well as the clinical significance of OxPLs and eNOS. METHODS: A prospective study was conducted on 95 children in the acute stage of KD (KD group). According to the presence of absence of CAL, the KD group was further divided into a CAL subgroup and a non-CAL (NCAL) subgroup. Thirty children with fever due to lower respiratory tract infection were enrolled as the fever group. Thirty healthy children who underwent physical examination were enrolled as the healthy control group. The above groups were compared in terms of general information and serum levels of OxPLs, eNOS and other laboratory indexes, and the correlation between OxPLs level and eNOS level was analyzed. RESULTS: The KD group had a significantly higher level of OxPLs and a significantly lower level of eNOS compared with the fever group and the healthy control group (P<0.05). After treatment, the children with KD had a significantly decreased OxPLs level and a significantly increased eNOS level (P<0.05). Compared with the NCAL subgroup, the CAL subgroup had a significantly higher level of OxPLs and a significantly lower level of eNOS (P<0.05). Among the children of KD, the level of OxPLs was negatively correlated with that of eNOS (rs=-0.353, P<0.05). CONCLUSIONS: Serum OxPLs and eNOS in the acute stage of KD may be involved in the development of CAL in children with KD, and therefore, they may be used as the biomarkers to predict CAL in these children.

ß-Catenin gain of function mutant in mouse periocular neural crest-derived mesenchymal cells impairs embryonic eyelid morphogenesis and leads to blepharophimosis syndrome in mice.

PURPOSE: The aberrant canonical Wnt-ß-catenin signaling can cause devastating outcomes of tissue morphogenesis and tumor formation. In this study, we examined the impact of overexpression of constitutive active ß-catenin in mouse periocular neural crest-derived mesenchymal cells during embryonic eyelid morphogenesis. METHODS: We expressed a stabilized ß-catenin in which the exon 3 of the Ctnnb1 gene was deleted in periocular neural crest (PONC)-derived eyelid stromal cells (Ctnnb1Δex3-PONC). Histopathological examinations were performed to examine the eyelid morphogenetic alterations in Ctnnb1Δex3-PONC mice. Immunohistochemical investigations for cell proliferation, apoptosis, and differentiation were also assessed. RESULTS: We discovered that nuclear accumulation of ß-catenin resulted in a reduction of nuclear Ki-67 and phospho-Erk1/2 expression levels and elevation of apoptosis in PONC cells during embryonic eyelid closure morphogenesis. Interestingly, however, the eyelid epithelial migration was not affected, which resulted in only eyelid epidermal closure but lacked underneath dermal formation at embryonic (E) day 16.5. The sequelae of Ctnnb1Δex3-PONC revealed the malformation of the eyelid margin and Meibomian gland and deficiency of Muller's smooth muscle fibers formation. Consequently, Ctnnb1Δex3-PONC mice manifested blepharophimosis syndrome at P21. CONCLUSION: Our data suggested that aberrant expression of ß-catenin gain of function in PONC interrupts the interplay between epithelium and stroma for the morphogenesis of eyelid closure during embryonic development.

Relationship between rs1410996 polymorphism of CFH gene and essential hypertension patients of Han from Yunnan Province.

OBJECTIVE: To explore the relationship between rs1410996 polymorphism of CFH gene and essential hypertension (EH) in the Yunnan Han population. METHODS: rs1410996 of CFH gene was genotyped based on the collected clinical phenotypes of the EH patients (n = 520) and healthy people (n = 494). RESULTS: On the genotype model and dominance model, there was no relationship between rs1410996 of CFH gene and EH after adjustment (P > 0.05). On the dominance model of male EH patients, the pulse pressure (PP) level of CC genotype carriers was higher than that of (CT + TT) genotype carriers after adjustment (P < 0.05). CONCLUSION: rs1410996 of CFH gene has no correlation with the genetic susceptibility to EH in the Yunnan Han population, but it is related to the PP level in male patients.

Gestational valproic acid exposure enhances facial stimulation-evoked cerebellar mossy fiber-granule cell transmission via GluN2A subunit-containing NMDA receptor in offspring mice.

Valproic acid (VPA) is one of the most effective antiepileptic drugs, and exposing animals to VPA during gestation has been used as a model for autism spectrum disorder (ASD). Numerous studies have shown that impaired synaptic transmission in the cerebellar cortical circuits is one of the reasons for the social deficits and repetitive behavior seen in ASD. In this study, we investigated the effect of VPA exposure during pregnancy on tactile stimulation-evoked cerebellar mossy fiber-granule cell (MF-GC) synaptic transmission in mice anesthetized with urethane. Three-chamber testing showed that mice exposed to VPA mice exhibited a significant reduction in social interaction compared with the control group. In vivo electrophysiological recordings revealed that a pair of air-puff stimulation on ipsilateral whisker pad evoked MF-GC synaptic transmission, N1, and N2. The evoked MF-GC synaptic responses in VPA-exposed mice exhibited a significant increase in the area under the curve (AUC) of N1 and the amplitude and AUC of N2 compared with untreated mice. Cerebellar surface application of the selective N-methyl-D-aspartate (NMDA) receptor blocker D-APV significantly inhibited facial stimulation-evoked MF-GC synaptic transmission. In the presence of D-APV, there were no significant differences between the AUC of N1 and the amplitude and AUC of N2 in the VPA-exposed mice and those of the untreated mice. Notably, blockade of the GluN2A subunit-containing, but not the GluN2B subunit-containing, NMDA receptor, significantly inhibited MF-GC synaptic transmission and decreased the AUC of N1 and the amplitude and AUC of N2 in VPA-exposed mice to levels similar to those seen in untreated mice. In addition, the GluN2A subunit-containing NMDA receptor was expressed at higher levels in the GC layer of VPA-treated mice than in control mice. These results indicate that gestational VPA exposure in mice produces ASD-like behaviors, accompanied by increased cerebellar MF-GC synaptic transmission and an increase in GluN2A subunit-containing NMDA receptor expression in the offspring.

Dimensionless analysis-based permeability model of reinforced concrete under tension.

Water permeability of reinforced concrete is essential for transportation of ingress ions inside concrete structures. The coupling effect of permeability and loading presents a challenge for the experimental simulation of water-permeate reinforced concrete subjected to tension. This renders the development of the model based on dimensionless analysis, using a series of experimental tests from an innovative experimental system that allows simultaneous measurement of permeability and crack width. The experiments focused on both ordinary concrete and high strength concrete under tension. The relationship between permeability and variables such as deformation, diameter of rebars, tensile load, and crack width under tension was formulated through multiple regression analysis using the testing data. The load to deformation characteristics determines the permeability of the concrete under tension. The proposed model accounts for the influence of continuous loading on permeability, as demonstrated by the robust analysis and proposed yield effective point. The robust analysis demonstrates that the diameter of the rebar, load, and crack width exert minimal influence on the permeability of concrete at lower significance levels. However, permeability variations become pronounced from 0.5 threshold, with significant changes observed between 0.5 and 0.9 thresholds. The findings indicate a differential impact of the variables on the permeability of concrete under tension. The yield-effective points delineate the relationship between the rebar diameter, load, and crack-width on the permeability of concrete with a threshold of 0.5, 0.5, and 0.58, respectively. At a threshold of 0.78, higher permeability will occur in the concrete, attributed to the prevalence of deformation. This deformation highlights the parameters with the most significant influence on the permeability of concrete under tension. The robust analysis and yield effective point derivative are useful parameters to measure concrete permeability and evaluate the behavior of the permeability model under tension.

Clinical efficacy of different therapeutic strategies in patients with spontaneous rupture of the esophagus: a multicenter retrospective cohort study.

BACKGROUND: The therapeutic strategy for patients with spontaneous rupture of the esophagus includes surgical repair, endoscopic therapy, supportive care, and others. However, no evidence exists to direct clinical decision-making regarding the choice of operative and nonoperative management. The aim of this study was to determine the clinical efficacy of different therapeutic strategies in both general and stratified patients. METHODS: This study retrospectively analyzed a consecutive cohort of 101 patients at nine tertiary referral hospital centers in China. Patients were divided into operative and nonoperative groups based on the initial treatment. Short-term outcomes, including 90-day mortality, length of hospital stay, and postoperative leakage were compared. Subgroup analysis was performed based on treatment timing and Pittsburgh perforation severity score (PSS). RESULTS: Of 101 patients, 60 (58.4%) underwent operative management. A significant difference of 90-day mortality between operative and nonoperative groups was observed (15.0% vs. 34.1%, P=0.031). Operative management tend to yield similar therapeutic benefits in timely (OR, 0.250; 95% CI, 0.05-1.14, P=0.073) and delayed (OR, 0.42; 95% CI, 0.12-1.47, P=0.175) treatment groups. Based on PSS stratification, operative management significantly decreased the risk of 90-day mortality (OR, 0.211; 95% CI, 0.064-0.701; P=0.011) for patients in low- and moderate-risk groups but may be detrimental for patients in high-risk group (OR, 1.333; 95% CI, 0.233-7.626; P=0.746). CONCLUSIONS: Operative management might be superior to nonoperative management for low- and moderate-risk patients with spontaneous rupture of the esophagus. However, for patients at high risks, operative management might not provide additional benefits compared with nonoperative management. Further research involving larger sample sizes is required for accurate patient stratification and conclusive evidence-based guideline.

Accelerated Charge Transfer through Interface Chemical Bonds in MoS2/TiO2 for Photocatalytic Conversion of Lignocellulosic Biomass to H2.

Solar photocatalytic H2 production from lignocellulosic biomass has attracted great interest, but it suffers from low photocatalytic efficiency owing to the absence of highly efficient photocatalysts. Herein, we designed and constructed ultrathin MoS2-modified porous TiO2 microspheres (MT) with abundant interface Ti-S bonds as photocatalysts for photocatalytic H2 generation from lignocellulosic biomass. Owing to the accelerated charge transfer related to Ti-S bonds, as well as the abundant active sites for both H2 and ●OH generation, respectively, related to the high exposed edge of MoS2 and the large specific surface area of TiO2, MT photocatalysts demonstrate good performance in the photocatalytic conversion of α-cellulose and lignocellulosic biomass to H2. The highest H2 generation rate of 849 µmol·g-1·h-1 and apparent quantum yield of 4.45% at 380 nm was achieved in α-cellulose aqueous solution for the optimized MT photocatalyst. More importantly, lignocellulosic biomass of corncob, rice hull, bamboo, polar wood chip, and wheat straw were successfully converted to H2 over MT photocatalysts with H2 generation rate of 10, 19, 36, 29, and 8 µmol·g-1·h-1, respectively. This work provides a guiding design approach to develop highly active photocatalysts via interface engineering for solar H2 production from lignocellulosic biomass.

Bioinformatic approaches of liquid-liquid phase separation in human disease.

ABSTRACT: Biomolecular aggregation within cellular environments via liquid-liquid phase separation (LLPS) spontaneously forms droplet-like structures, which play pivotal roles in diverse biological processes. These structures are closely associated with a range of diseases, including neurodegenerative disorders, cancer and infectious diseases, highlighting the significance of understanding LLPS mechanisms for elucidating disease pathogenesis, and exploring potential therapeutic interventions. In this review, we delineate recent advancements in LLPS research, emphasizing its pathological relevance, therapeutic considerations, and the pivotal role of bioinformatic tools and databases in facilitating LLPS investigations. Additionally, we undertook a comprehensive analysis of bioinformatic resources dedicated to LLPS research in order to elucidate their functionality and applicability. By providing comprehensive insights into current LLPS-related bioinformatics resources, this review highlights its implications for human health and disease.

Hong Guo Ginseng Guo (HGGG) protects against kidney injury in diabetic nephropathy by inhibiting NLRP3 inflammasome and regulating intestinal flora.

BACKGROUND: Diabetic nephropathy (DN) is one of the most serious complications of diabetes which leads to end-stage renal failure and approximately one-third of patients need dialysis. There is still a lack of effective and specific treatment for DN. Searching new drugs from natural foods is an alternative approach to treat diabetes and its complications. Hong Guo Ginseng Guo (HGGG), a berry with palatability and nutritional benefits, has exhibited medicinal properties to mitigate the progression of DN. PURPOSE: This study investigates the effects of HGGG on streptozotocin (STZ)-induced diabetic nephropathy (DN) in rats and elucidates the mechanisms underlying its reno-protective and diabetes management benefits. METHODS: The LC-MS spectra method identified the primary ingredients in HGGG. To induce DN, male Sprague-Dawley (SD) rats received a single intraperitoneal injection of 75 mg/kg STZ. Over an eight-week treatment period, we assessed biochemical parameters including blood glucose, urine albumin-to-creatinine ratio (UACR), blood urea nitrogen (BUN), and urine N-acetyl-beta-d-glucosaminidase (NAG). Tissue pathology was examined using Masson's trichrome, Periodic Acid-Schiff (PAS), and Hematoxylin-Eosin (H&E) stains. We analyzed pro-inflammatory mediators and tissue fibrosis extent using Western blotting and immunohistochemistry. Gut microbiota composition was characterized via 16S rDNA sequencing. RESULTS: Seventeen chemical compounds were identified, with lobetyolin, luteolin, and rutin highlighted as the primary active elements. HGGG extract appeared to confer renal protection, demonstrated by improvements in UACR, BUN, and urine NAG levels. The reno protective effects in HGGG-treated DN rats were linked to reduced renal fibrosis and inhibition of the NLRP3 inflammasome. Additionally, HGGG administration improved gut barrier integrity and altered the gut microbiota in DN rats, increasing the relative abundance of beneficial bacteria known for regulating polyamines and producing short-chain fatty acids (SCFAs), including Ruminococcus, Barnesiella_sp, Anaerovoracaceae, and Prevotellaceae_NK3B31. Meanwhile, treatment with HGGG decreasing the presence of Oscillospira, potential pathogens responsible for producing lipopolysaccharide (LPS). CONCLUSION: HGGG has potential as a beneficial fruit for managing diabetes and its associated complications through modulation of the gut microbiota.