Omega-3 PUFAs slow organ aging through promoting energy metabolism.

Energy metabolism disorder, mainly exhibiting the inhibition of fatty acid degradation and lipid accumulation, is highly related with aging acceleration. However, the intervention measures are deficient. Here, we reported Omega-3 polyunsaturated fatty acids (Omega-3 PUFAs), especially EPA, exerted beneficial effects on maintaining energy metabolism and lipid homeostasis to slow organ aging. As the endogenous agonist of peroxisome proliferator-activated receptor α (PPARα), Omega-3 PUFAs significantly boosted fatty acid ß-oxidation and ATP production in multiple aged organs. Consequently, Omega-3 PUFAs effectively inhibited age-related pathological changes, preserved organ function, and retarded aging process. The beneficial effects of Omega-3 PUFAs were also testified in mfat-1 transgenic mice, which spontaneously generate abundant endogenous Omega-3 PUFAs. In conclusion, our study innovatively demonstrated Omega-3 PUFAs administration in diet slow aging through promoting energy metabolism. The supplement of Omega-3 PUFAs or fat-1 transgene provides a promising therapeutic approach to promote healthy aging in the elderly.

The impact of lactic acid bacteria inoculation on the fermentation and metabolomic dynamics of indigenous Beijing douzhi microbial communities.

Background: Douzhi, a traditional Chinese fermented beverage, features microbial communities primarily composed of lactic acid bacteria (LAB). As fermented foods continue to gain recognition and popularity, douzhi is attracting growing interest. However, investigation of the critical aspects of douzhi's fermentation processes, including fermentation characteristics and microbial community dynamics, remains vital for enhancing food safety and quality for douzhi, as well as for similar fermented food products. Method: In this study, we collected douzhi microbial communities from four chain stores, using them as fermentation starter cultures. The microbial dynamics of the fermentation were analyzed, focusing on the inoculation of LAB strains and the transition from a mung bean-based matrix to skimmed milk. The metabolomic profiles of the fermented mung bean matrices were also studied. Results: Douzhi samples obtained from representative chain stores were found to be overwhelmingly dominated by LAB. When inoculated along with the douzhi community, both LAB strains exhibited notable and substantial reductions in the pH value of the designated mung bean matrices compared to those inoculated indigenous microbiota. Specifically, Lactiplantibacillus plantarum CGMCC 1.1856 retained its population, whereas Pediococcus pentosaceus CGMCC 1.2695 exhibited a decrease in relative abundance. Using skimmed milk as a fermentation substrate instead of the mung bean matrix resulted in significant shifts in microbial communities, particularly leading to an increase in Escherichia sp. The metagenomic analyses and functional predictions illustrated that various metabolic functions were enhanced during the fermentation process due to LAB inoculation. The liquid chromatography-mass spectrometry based metabolomic analysis revealed that the inoculation of Lactiplantibacillus plantarum and Pediococcus pentosaceus in mung bean matrix did not introduce new metabolites but significantly altered the concentration and profile of existing metabolites, especially increased low molecular carbohydrates, which may enhance the nutritional potential of the fermented product. Discussion: This study examines the microbial dynamics of douzhi microbiota fermentation, emphasizing the role of lactic acid bacteria in enhancing fermentation activity and metabolite profiles. These insights contribute to improving manufacturing processes and ensuring the safety and quality of douzhi and similar fermented foods.

An intelligent NIR-IIb-responsive lanthanide@metal-organic framework core-shell nanocatalyst for combined deep-tumor therapy.

The ground-breaking combination of photodynamic therapy (PDT) and photothermal therapy (PTT) has attracted much attention in medical fields as an effective method for fighting cancer. However, evidence suggests that the therapy efficiency is still limited by shallow light penetration depth and poor photosensitizer loading capacity. Herein, we constructed an upconversion nanoparticle@Zr-based metal-organic framework@indocyanine green molecule (UCNPs@ZrMOF@ICG) nanocomposite to integrate 1532 nm light-triggered PDT and 808 nm light-mediated PTT. NaLnF4 nanoparticles are designed to emit upconversion luminescence (UCL) under 1532 nm laser excitation, which is consistent with the absorption spectra of the ZrMOF. Benefiting from the excellent energy transfer efficiency, the ZrMOF can absorb visible light from the UCNPs and then catalyze O2 into 1O2 for deep tissue PDT. To achieve combination therapy, the clinically approved ICG nanocomposite was introduced as a photothermal agent for PTT under 808 nm laser irradiation, and the photothermal conversion efficiency was calculated to be ∼28%. The designed nanosystems facilitate efficient deep-tissue tumor treatment by integrating PDT with PTT. Ultimately, this study creates a multifunctional nanocomposite by combining 1532 nm light-triggered deep tissue PDT and near-infrared (NIR) light-driven PTT for personalized cancer therapy.

Long-term thermal acclimation enhances heat resistance of Hong Kong catfish (Clarias fuscus) by modulating gill tissue structure, antioxidant capacity and immune metabolic pathways.

The rapid temperature changes caused by global warming significantly challenge fish survival by affecting various biological processes. Fish generally mitigate stress through physiological plasticity, but when temperature changes exceed their tolerance limits, even adaptable species like Siluriformes can experience internal disruptions. This study investigates the effects of extreme thermal climate on Hong Kong catfish (Clarias fuscus), native to tropical and subtropical regions. C. fuscus were exposed to normal temperature (NT, 26 ℃) or high temperature (HT, 34 ℃) condition for 90 days. Subsequently, histological, biochemical, and transcriptomic changes in gill tissue were observed after exposure to acute high temperatures (34 ℃) and subsequent temperature recovery (26 ℃). Histological analysis revealed that C. fuscus in the HT group exhibited less impact from sudden temperature shifts compared to the NT group, as they adapted by reducing the interlamellar cell mass (ILCM) and lamellae thickness (LT) of gill tissue, thereby mitigating the aftermath of acute heat shock. Biochemical analysis showed that catalase (CAT) activity in the high temperature group continued to increase, while malondialdehyde (MDA) levels decreased, suggesting establishment of a new oxidative balance and enhanced environmental adaptability. Transcriptome analysis identified 520 and 463 differentially expressed genes in the NT and HT groups, respectively, in response to acute temperature changes. Enrichment analysis highlighted that in response to acute temperature changes, the NT group inhibited apoptosis and ferroptosis by regulating the activity of alox12, gclc, and hmox1a, thereby attenuating the adverse effects of heat stress. Conversely, the HT group increased the activity of pfkma and pkma to provide sufficient energy for tissue repair. The higher degree of heat shock protein (Hsp) response in NT group also indicated more severe heat stress injury. These findings demonstrate alterations in gill tissue structure, regulation of oxidative balance, and the response of immune metabolic pathways to acute temperature fluctuations in C. fuscus following thermal exposure, suggesting potential avenues for further exploration into the thermal tolerance plasticity of fish adapting to global warming.

Response characteristics of soil microorganisms under strong disturbance conditions in the riparian zone of the three Gorges reservoir Area.

The normal operation of the Three Gorges Reservoir, which involves periodic water storage and discharge, has led to strong disturbances in environmental conditions that alter soil microbial habitats in the riparian zones. Riparian zones are an important part of controlling pollution in the Three Gorges Reservoir area, since they act as a final ecological barrier that intercepts pollutants. Meanwhile, monitoring the health of microbial communities in the riparian zone is crucial for maintaining the ecological security of the reservoir area. We specifically investigate the Daning River, which are tributaries of the Three Gorges Reservoir and have typical riparian zones. Soil samples from these areas were subjected to high-throughput sequencing of 16S rRNA genes and 18S rRNA genes, in order to obtain the characteristics of the present microbial communities under strong disturbances in the riparian zones. We studied the characteristics and distribution patterns of microbial communities and their relationship with soil physicochemical properties. The study results indicate that microbial communities exhibit high diversity and evenness, and spatial heterogeneity is present. The ASV dataset contains many sequences not assigned to known genera, suggesting the presence of new fungal genera in the riparian zone. Redundancy analysis (RDA) revealed that pH and NH 4 + -N were the primary environmental factors driving bacterial community variation in the riparian zone, while pH, total carbon (TC) content, and NO 3 - -N were identified as the main drivers of soil archaeal community variation.

Template Selection Strategy for Synthesis of One-Dimensional CrSbSe3 Ferromagnetic Semiconductor Nanoribbons.

CrSbSe3─the only experimentally validated one-dimensional (1D) ferromagnetic semiconductor─has recently attracted significant attention. However, all reported synthesis methods for CrSbSe3 nanocrystals are based on top-down methods. Here we report a template selection strategy for the bottom-up synthesis of CrSbSe3 nanoribbons. This strategy relies on comparing the formation energies of potential binary templates to the ternary target product. It enables us to select Sb2Se3 with the highest formation energy, along with its 1D crystal structure, as the template instead of Cr2Se3 with the lowest formation energy, thereby facilitating the transformation from Sb2Se3 to CrSbSe3 by replacing half of the Sb atoms in Sb2Se3 with Cr atoms. The as-prepared CrSbSe3 nanoribbons exhibit a length of approximately 5 µm, a width ranging from 80 to 120 nm, and a thickness of about 5 nm. The single CrSbSe3 nanoribbon presents typical semiconductor behavior and ferromagnetism, confirming the intrinsic ferromagnetism in the 1D CrSbSe3 semiconductor.

Molecular Evolutionary Dynamics of Coxsackievirus A6 Causing Hand, Foot, and Mouth Disease From 2021 to 2023 in China: Genomic Epidemiology Study.

Background: Hand, foot, and mouth disease (HFMD) is a global public health concern, notably within the Asia-Pacific region. Recently, the primary pathogen causing HFMD outbreaks across numerous countries, including China, is coxsackievirus (CV) A6, one of the most prevalent enteroviruses in the world. It is a new variant that has undergone genetic recombination and evolution, which might not only induce modifications in the clinical manifestations of HFMD but also heighten its pathogenicity because of nucleotide mutation accumulation. Objective: The study assessed the epidemiological characteristics of HFMD in China and characterized the molecular epidemiology of the major pathogen (CV-A6) causing HFMD. We attempted to establish the association between disease progression and viral genetic evolution through a molecular epidemiological study. Methods: Surveillance data from the Chinese Center for Disease Control and Prevention from 2021 to 2023 were used to analyze the epidemiological seasons and peaks of HFMD in Henan, China, and capture the results of HFMD pathogen typing. We analyzed the evolutionary characteristics of all full-length CV-A6 sequences in the NCBI database and the isolated sequences in Henan. To characterize the molecular evolution of CV-A6, time-scaled tree and historical population dynamics regarding CV-A6 sequences were estimated. Additionally, we analyzed the isolated strains for mutated or missing amino acid sites compared to the prototype CV-A6 strain. Results: The 2021-2023 epidemic seasons for HFMD in Henan usually lasted from June to August, with peaks around June and July. The monthly case reporting rate during the peak period ranged from 20.7% (4854/23,440) to 35% (12,135/34,706) of the total annual number of cases. Analysis of the pathogen composition of 2850 laboratory-confirmed cases identified 8 enterovirus serotypes, among which CV-A6 accounted for the highest proportion (652/2850, 22.88%). CV-A6 emerged as the major pathogen for HFMD in 2022 (203/732, 27.73%) and 2023 (262/708, 37.01%). We analyzed all CV-A6 full-length sequences in the NCBI database and the evolutionary features of viruses isolated in Henan. In China, the D3 subtype gradually appeared from 2011, and by 2019, all CV-A6 virus strains belonged to the D3 subtype. The VP1 sequences analyzed in Henan showed that its subtypes were consistent with the national subtypes. Furthermore, we analyzed the molecular evolutionary features of CV-A6 using Bayesian phylogeny and found that the most recent common ancestor of CV-A6 D3 dates back to 2006 in China, earlier than the 2011 HFMD outbreak. Moreover, the strains isolated in 2023 had mutations at several amino acid sites compared to the original strain. Conclusions: The CV-A6 virus may have been introduced and circulating covertly within China prior to the large-scale HFMD outbreak. Our laboratory testing data confirmed the fluctuation and periodic patterns of CV-A6 prevalence. Our study provides valuable insights into understanding the evolutionary dynamics of CV-A6.

Cannabinoid receptor 2 plays a key role in renal fibrosis through inhibiting lipid metabolism in renal tubular cells.

AIMS: Renal fibrosis is a common feature in various chronic kidney diseases (CKD). Tubular cell damage is a main characterization which results from dysregulated fatty acid oxidation (FAO) and lipid accumulation. Cannabinoid Receptor 2 (CB2) contributes to renal fibrosis, however, its role in FAO dysregulation in tubular cells is not clarified. In this study, we found CB2 plays a detrimental role in lipid metabolism in tubular cells. METHODS: CB2 knockout mice were adopted to establish a folic acid-induced nephropathy (FAN) model. CB2-induced FAO dysfunction, lipid deposition, and fibrogenesis were assessed in vivo and vitro. To explore molecular mechanisms, ß-catenin inhibitors and peroxisome proliferator-activated receptor alpha (PPARα) activators were also used in CB2-overexpressed cells. The mediative role of ß-catenin in CB2-inhibited PPARα and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) activation was analyzed. RESULTS: CB2 activates ß-catenin signaling, resulting in the suppression of PPARα/PGC-1α axis. This decreased FAO functions and led to lipid droplet formation in tubular cells. CB2 gene ablation effectively mitigated FAO dysfunction, lipid deposition and uremic toxins accumulation in FAN mice, consequently retarding renal fibrosis. Additionally, inhibition to ß-catenin or PPARα activation could greatly inhibit lipid accumulation and fibrogenesis induced by CB2. CONCLUSIONS: This study highlights CB2 disrupts FAO in tubular cells through ß-catenin activation and subsequent inhibition on PPARα/PGC-1α activity. Targeted inhibition on CB2 offers a perspective therapeutic strategy to fight against renal fibrosis.

Imbalance of Th17 cells, Treg cells and associated cytokines in patients with systemic lupus erythematosus: a meta-analysis.

Objective: This article aims to investigate the changes of T helper 17 (Th17) cells, regulatory T (Treg) cells and their associated cytokines in patients with systemic lupus erythematosus (SLE). Methods: Multiple databases were investigated to identify articles that explored Th17 cells, Treg cells and relevant cytokines in SLE patients. A random effects model was used for calculating pooled standardized mean differences. Stata version 15.0 was utilized to conduct the meta-analysis. Results: The levels of Th17 cells, IL-17, IL-6, IL-21 and IL-10 were higher in SLE patients than in healthy controls (HCs), but the TGF-ß levels were lower. The percentage of Treg cells was lower than HCs in SLE individuals older than 33. Among studies that had 93% or lower females, the percentage of Th17 cells was greater in patients than in HCs. However, the percentage of Treg cells was lower when the proportion of females was less than 90%. Patients with lupus nephritis or active SLE had an increased proportion of Th17 cells and a decreased proportion of Treg cells. Conclusions: The increased level of Th17 cells and related cytokines could be the main reason for the elevated Th17/Treg ratio in SLE. The percentages of Th17 and Treg cells were associated with gender, age, disease activity and kidney function. Furthermore, the reduced proportions of Treg cells may primarily result in a rise in the Th17/Treg ratio in older or active SLE patients. Systematic Review Registration: https://www.crd.york.ac.uk/prospero, identifier CRD42023454937.

ADH4-a potential prognostic marker for hepatocellular carcinoma with possible immune-related implications.

OBJECTIVE: This study aims to explore ADH4 expression in hepatocellular carcinoma (HCC), its prognostic impact, and its immune correlation to provide novel insights into HCC prognostication and treatment. METHODS: HCC prognostic marker genes were rigorously selected using GEO database, Lasso regression, GEPIA, Kaplan-Meier and pROC analyses. The expression of interested markers (ADH4, DNASE1L3, RDH16, LCAT, HGFAC) in HCC and adjacent tissues was assessed by Immunohistochemistry (IHC). We observed that ADH4 exhibited low expression levels in liver cancer tissues and high expression levels in normal liver tissues. However, the remaining four genes did not manifest any statistically significant differences between hepatocellular carcinoma (HCC) tissue and adjacent non-cancerous tissue. Consequently, ADH4 became the primary focus of our research. ADH4 expression was validated by signed-rank tests and unpaired Wilcoxon rank sum tests across pan-cancer and HCC datasets. Clinical significance and associations with clinicopathological variables were determined using Kaplan-Meier, logistic regression and Cox analyses on TCGA data. The ADH4-related immune responses were explored by Spearman correlation analysis using TIMER2 data. CD68, CD4, and CD19 protein levels were confirmed by IHC in HCC and non-cancerous tissues. RESULTS: ADH4 showed significant downregulation in various cancers, particularly in HCC. Moreover, low ADH4 expression was associated with clinicopathological variables and served as an independent prognostic marker for HCC patients. Additionally, ADH4 affects a variety of biochemical functions and may influence cancer development, prognosis, and treatment by binding to immune cells. Furthermore, at the immune level, the low expression pattern of ADH4 is TME-specific, indicating that ADH4 has the potential to be used as a target for cancer immunotherapy. CONCLUSION: This study highlights the diagnostic, prognostic and immunomodulatory roles of ADH4 in HCC. ADH4 could serve as a valuable biomarker for HCC diagnosis and prognosis, as well as a potential target for immunotherapeutic interventions.

Unraveling the Disulfide-Carbonyl n → π* Interactions in a Gas Phase Molecular Complex and Proteins.

The weak contacts between disulfide linkages and carbonyl groups are anticipated to be important in determining the structure and function of enzymes and proteins. However, the characteristics of the disulfide-carbonyl n → π* (nSS → π* C═O) interactions remain unexplored. Herein, we investigated the nSS → π* C═O interactions in the gas phase and in proteins. Rotational spectroscopic investigation of a model complex of allyl methyl disulfide with formaldehyde identified two structures, both of which are stabilized through a dominant nSS → π* C═O interaction. Surveys of the Protein Data Bank revealed the occurrence of 18 675 nSS → π* C═O interactions associated with 15 320 disulfide bonds in 7105 protein structures. Further theoretical analyses characterize the bonding nature of the nSS → π* C═O interactions. This study provides an in-depth understanding of the stabilizing effect of the nSS → π* C═O interactions in small molecular complexes and biomacromolecules.

Associations of oxidative balance score with lumbar spine osteopenia in 20-40 years adults: NHANES 2011-2018.

PURPOSE: Current research suggests that oxidative stress may decrease bone mineral density (BMD) by disrupting bone metabolism balance. However, no study investigated the relationship between systemic oxidative stress status and adult BMD. This study aims to investigate whether oxidative balance score (OBS) is associated with BMD in adults under 40. METHODS: 3963 participants were selected from the National Health and Nutrition Survey (NHANES) from 2011 to 2018. OBS is scored based on 20 dietary and lifestyle factors. Weighted multiple logistic regression and restricted cubic splines were used to assess the correlation between OBS and osteopenia. RESULTS: After adjusting for confounding factors, the weighted logistic regression results showed that compared with the first tertile of OBS, the highest tertile had a 38% (OR: 0.62, 95% CI: 0.47-0.82) lower risk of osteopenia. The restrictive cubic spline curve indicates a significant nonlinear correlation between OBS and the risk of osteopenia. CONCLUSION: The research findings emphasize the relationship between OBS and the risk of osteopenia in young adults. Adopting an antioxidant diet and lifestyle may help young adults to maintain bone mass.

N6-methyladenosine modified circPAK2 promotes lymph node metastasis via targeting IGF2BPs/VEGFA signaling in gastric cancer.

Circular RNAs (circRNAs) have emerged as key regulators of cancer occurrence and progression, as well as promising biomarkers for cancer diagnosis and prognosis. However, the potential mechanisms of circRNAs implicated in lymph node (LN) metastasis of gastric cancer remain unclear. Herein, we identify a novel N6-methyladenosine (m6A) modified circRNA, circPAK2, which is significantly upregulated in gastric cancer tissues and metastatic LN tissues. Functionally, circPAK2 enhances the migration, invasion, lymphangiogenesis, angiogenesis, epithelial-mesenchymal transition (EMT), and metastasis of gastric cancer in vitro and in vivo. Mechanistically, circPAK2 is exported by YTH domain-containing protein 1 (YTHDC1) from the nucleus to the cytoplasm in an m6A methylation-dependent manner. Moreover, increased cytoplasmic circPAK2 interacts with Insulin-Like Growth Factor 2 mRNA-Binding Proteins (IGF2BPs) and forms a circPAK2/IGF2BPs/VEGFA complex to stabilize VEGFA mRNA, which contributes to gastric cancer vasculature formation and aggressiveness. Clinically, high circPAK2 expression is positively associated with LN metastasis and poor prognosis in gastric cancer. This study highlights m6A-modified circPAK2 as a key regulator of LN metastasis of gastric cancer, thus supporting circPAK2 as a promising therapeutic target and prognostic biomarker for gastric cancer.

Rapid assessment of heavy metal accumulation capability of Sedum alfredii using hyperspectral imaging and deep learning.

Hyperaccumulators are the material basis and key to the phytoremediation of heavy metal contaminated soils. Conventional methods for screening hyperaccumulators are highly dependent on the time- and labor-consuming sampling and chemical analysis. In this study, a novel spectral approach assisted with multi-task deep learning was proposed to streamline accumulating ecotype screening, heavy metal stress discrimination, and heavy metals quantification in plants. The significant Cd/Zn co-hyperaccumulator Sedum alfredii and its non-accumulating ecotype were stressed by Cd, Zn, and Pb. Spectral images of leaves were rapidly acquired by hyperspectral imaging. The self-designed deep learning architecture was composed of a shallow network (ENet) for accumulating ecotype identification, and a multi-task network (HMNet) for heavy metal stress type and accumulation prediction simultaneously. To further assess the robustness of the networks, they were compared with conventional machine learning models (i.e., partial least squares (PLS) and support vector machine (SVM)) on a series of evaluation metrics of classification, multi-label classification, and regression. S. alfredii with heavy metals accumulation capability was identified by ENet with 100 % accuracy. HMNet reduced overfitting and outperformed machine learning models with the average exact match ratio (EMR) of heavy metal stress discrimination increased by 7.46 %, and residual prediction deviations (RPD) of heavy metal concentrations prediction increased by 53.59 %. The method succeeded in rapidly and accurately discriminating heavy metal stress with EMRs over 91 % and accuracies over 96 %, and in predicting heavy metals accumulation with an average RPD of 3.29 for Zn, 2.57 for Cd, and 2.53 for Pb, indicating the satisfactory practicability and potential for sensing heavy metals accumulation. This study provides a relatively novel spectral method to facilitate hyperaccumulator screening and heavy metals accumulation prediction in the phytoremediation process.

[Analysis of risk factors for long-term overactive bladder after radical prostatectomy].

OBJECTIVE: To analyze the incidence and progression of overactive bladder (OAB) symptoms following radical prostatectomy for prostate cancer patients and to identify related risk factors. METHODS: A retrospective study was conducted on 263 local stage prostate cancer patients who underwent radical prostatectomy at Peking University Third Hospital from January 2013 to May 2017. Clinical baseline information, comprehensive imaging features, perioperative parameters, preoperative urinary control status, pathological diagnosis, and the incidence of OAB within one year postoperatively were collected and analyzed. In the imaging features, two parameters were defined: Bladder wall thickness (BWT) and bladder mucosal smoothness (BMS), which were used to predict the occurrence of OAB. Patients were evaluated based on their clinical baseline characteristics, including age, body mass index (BMI), comorbidities, and prostate-specific antigen (PSA) levels. The imaging characteristics were assessed using preoperative MRI, focusing on BWT and BMS. Perioperative parameters included operative time, blood loss, and length of hospital stay. The OAB symptoms were assessed using the overactive bladder symptom score (OABSS) and the international prostate symptom score (IPSS). These scores were correlated with the postoperative incidence of OAB. RESULTS: Among the 263 patients who underwent radical prostatectomy, 52 (19.8%) exhibited OAB within one year postoperatively. Of the 40 patients with preoperative OAB symptoms, 17 (42.5%) showed remission postoperatively, while 23 (57.5%) had persistent symptoms. Additionally, 29 patients developed new-onset OAB, accounting for 55.77% of all postoperative OAB cases. Univariate analysis indicated that BWT, BMS, OABSS, and IPSS score were all associated with the occurrence of postoperative OAB. Further multivariate analysis identified BMS as an independent risk factor for long-term OAB (P < 0.001). CONCLUSION: Long-term postoperative overactive bladder is a common complication following radical prostatectomy. The findings suggest that preoperative MRI measurements of bladder wall thickness and bladder mucosal smoothness during bladder filling phase can predict the risk of OAB occurrence postoperatively. Identifying these risk factors preoperatively can help in counseling patients about potential complications and in developing strategies to mitigate the risk of developing OAB after surgery. Early detection and management of these parameters might improve the quality of life for patients undergoing radical prostatectomy.

B4 suppresses lymphoma progression by inhibiting fibroblast growth factor binding protein 1 through intrinsic apoptosis.

Lymphoma positions as the fifth most common cancer, in the world, reporting remarkable deaths every year. Several promising strategies to counter this disease recently include utilizing small molecules that specifically target the lymphoma cellular proteins to overwhelm its progression. FGFBP1 is a soluble intracellular protein that progresses cancer cell proliferation and is upregulated in several cancers. Therefore, inhibiting FGFBP1 could significantly slow down lymphoma progression through triggering apoptosis. Thus, in this study, a flavonoid B4, isolated from Cajanus cajan, has been investigated for its effects of B4 on lymphoma, specifically as an FGFBP1 inhibitor. B4 could selectively hinder the growth of lymphoma cells by inducing caspase-dependent intrinsic apoptosis through G1/S transition phase cell cycle arrest. RNA sequencing analysis revealed that B4 regulates the genes involved in B-cell proliferation and DNA replication by inhibiting FGFBP1 in vitro. B4 increases the survival rate of lymphoma mice. B4 also represses the growth of patient-derived primary lymphoma cells through FGFBP1 inhibition. Drug affinity responsive target stability experimentations authorize that B4 powerfully binds to FGFBP1. The overexpression of FGFBP1 raises the pharmacological sensitivity of B4, supplementing its specific action on lymphoma cells. This study pioneers the estimation of B4 as a possible anticancer agent for lymphoma treatment. These outcomes highlight its selective inhibitory effects on lymphoma cell growth by downregulating FGFBP1 expression through intrinsic apoptosis, causing mitochondrial and DNA damage, ultimately leading to the inhibition of lymphoma progression. These suggest B4 may be a novel FGFBP1 inhibitor for the lymphoma treatment.

Perturbations in gut microbiota composition in schizophrenia.

Schizophrenia is a severe, complex and long-term psychiatric disorder with unclear etiology. Gut microbes influence the central nervous system via the gut-brain axis. Consequently, investigations of the relationship between gut microbes and schizophrenia are warranted. This study involved 29 patients with schizophrenia and 30 age-matched normal controls. After 16S rRNA gene sequencing and whole-genome shotgun metagenomic sequencing, we analyzed microbial diversity, composition, and function. According to 16S rRNA and metagenomic gene sequencing results, patients with schizophrenia had higher abundances of Clostridium and Megasphaera. Functional analysis showed that sphingolipid, phosphonates and phosphinates, as well as glutamine metabolism were associated with the occurrence and development of schizophrenia. Our data suggest that the gut microbiota exerts an effect on patients with schizophrenia, providing valuable insights into the potential regulation of in the context of this disorder.

The use of the self-organizing map (SOM) methodology to study the dissolved organic matter (DOM) in different water body types.

This study investigated the characteristics of dissolved organic matter (DOM) in two distinct water bodies, through the utilization of three-dimensional fluorescence spectroscopy coupled with self-organizing map (SOM) methodology. Specifically, this analysis concentrated on neurons 3, 14, and 17 within the SOM model, identifying notable differences in the DOM compositions of a coal subsidence water body (TX) and the MaChang Reservoir (MC). The humic substance content of DOM TX exceeded that of MC. The origin of DOM in TX was primarily linked to agricultural inputs and rainfall runoff, whereas the DOM in MC was associated with human activities, displaying distinctive autochthonous features and heightened biological activity. Principal component analysis revealed that humic substances dominated the DOM in TX, while the natural DOM in MC was primarily autochthonous. Furthermore, a multiple linear regression model (MLR) determined that external pollution was responsible for 99.11% of variation in the humification index (HIX) of water bodies.

NG2-Glia Cause Diabetic Blood-Brain Barrier Disruption by Secreting MMP-9.

Background: Disorders of the blood-brain barrier (BBB) arising from diabetes mellitus are closely related to diabetic encephalopathy. Previous research has suggested that neuron-glia antigen 2 (NG2)-glia plays a key role in maintaining the integrity of the BBB. However, the mechanism by which NG2-glia regulates the diabetic BBB remains unclear. Methods: Type 2 diabetes mellitus (T2DM) db/db mice and db/m mice were used. Evans-Blue BBB permeability tests and transmission electron microscopy techniques were applied. Tight junction proteins were assessed by immunofluorescence and transmission electron microscopy. NG2-glia number and signaling pathways were evaluated by immunofluorescence. Detection of matrix metalloproteinase-9 (MMP-9) in serum was performed using enzyme-linked immunosorbent assay (ELISA). Results: In T2DM db/db mice, BBB permeability in the hippocampus significantly increased from 16 weeks of age, and the structure of tight junction proteins changed. The number of NG2-glia in the hippocampus of db/db mice increased around microvessels from 12 weeks of age. Concurrently, the expression of MMP-9 increased in the hippocampus with no change in serum. Sixteen- week-old db/db mice showed activation of the Wnt/ß-catenin signaling in hippocampal NG2-glia. Treatment with XAV-939 improved structural and functional changes in the hippocampal BBB and reduced MMP-9 secretion by hippocampal NG2-glia in db/db mice. It was also found that the upregulation of ß-catenin protein in NG2-glia in the hippocampus of 16-week-old db/db mice was significantly alleviated by treatment with XAV-939. Conclusion: The results indicate that NG2-glia can lead to structural and functional disruption of the diabetic BBB by activating Wnt/ß-catenin signaling, upregulating MMP-9, and degrading tight junction proteins.

A Prediction Model for Assessing the Efficacy of Thermal Ablation in Treating Benign Thyroid Nodules ≥ 2 cm: A Multi-Center Retrospective Study.

OBJECTIVES: To develop and validate a prediction model utilizing clinical and ultrasound (US) data for preoperative assessment of efficacy following US-guided thermal ablation (TA) in patients with benign thyroid nodules (BTNs) ≥ 2 cm. MATERIALS AND METHODS: We retrospectively assessed 962 patients with 1011 BTNs who underwent TA at four tertiary centers between May 2018 and July 2022. Ablation efficacy was categorized into therapeutic success (volume reduction rate [VRR] > 50%) and non-therapeutic success (VRR ≤ 50%). We identified independent factors influencing the ablation efficacy of BTNs ≥ 2 cm in the training set using multivariate logistic regression. On this basis, a prediction model was established. The performance of model was further evaluated by discrimination (area under the curve [AUC]) in the validation set. RESULTS: Of the 1011 nodules included, 952 (94.2%) achieved therapeutic success at the 12-month follow-up after TA. Independent factors influencing VRR > 50% included sex, nodular composition, calcification, volume, and largest diameter (all p < 0.05). The prediction equation was established as follows: p = 1/1 + Exp∑[8.113 -2.720 × (if predominantly solid) -2.790 × (if solid) -1.275 × (if 10 mL < volume ≤ 30mL) -1.743 × (if volume > 30 mL) -1.268 × (if with calcification) -2.859 × (if largest diameter > 3 cm) +1.143 × (if female)]. This model showed great discrimination, with AUC of 0.908 (95% confidence interval [CI]: 0.868-0.947) and 0.850 (95% CI: 0.748-0.952) in the training and validation sets, respectively. CONCLUSIONS: A clinical prediction model was successfully developed to preoperatively predict the therapeutic success of BTNs larger than 2 cm in size following US-guided TA. This model aids physicians in evaluating treatment efficacy and devising personalized prognostic plans.