MicroRNA-29b Plays a Vital Role in Podocyte Injury and Glomerular Diseases through Inducing Mitochondrial Dysfunction.

Diabetic kidney disease (DKD) is becoming the most leading cause of end-stage renal disease (ESRD). Podocyte injury plays a critical role in DKD progression. Notably, mitochondrial dysfunction is crucial for podocyte injury. MicroRNAs (miRNAs) involves in various kidney diseases. Herein, we discovered miR-29b was induced in the urine of 126 patients with DKD (stage I and II), and negatively correlated with kidney function and podocyte homeostasis. Mechanically, miR-29b targeted peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), a co-activator of transcription factors regulating mitochondrial biogenesis and energy metabolism. In vitro, ectopic miR-29b downregulated PGC-1α and promoted podocyte injury, while inhibition of miR-29b alleviated podocyte injury. Consistently, inhibition of miR-29b mitigated podocyte injury and preserved kidney function in ADR nephropathy and db/db mice, and overexpression of miR-29b accelerated disease. Knockout miR-29b specifically in podocyte inhibited mitochondrial dysfunction and podocyte injury. These results revealed miR-29b plays a crucial role in mitochondrial dysfunction through targeted inhibition on PGC-1α, leading to podocyte injury and DKD progression. Importantly, miR-29b could serve as a novel biomarker of podocyte injury and assists to early diagnose DKD.

Virus Infection Induces Immune Gene Activation with CTCF Anchored Enhancers and Chromatin Interactions in Pig Genome.

Chromatin organization is important for gene transcription in pig genome. However, its three-dimensional (3D) structure and dynamics are much less investigated than those in human. Here we applied the long-reads chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) method to map the whole-genome chromatin interactions mediated by CCCTC-binding factor (CTCF) and RNA polymerase Ⅱ (RNAPⅡ or POLⅡ) in porcine macrophage cells before and after polyinosinic-polycytidylic acid [Poly(I:C)] induction. Our results revealed that Poly(I:C) induction impacts the 3D genome organization in the 3D4/21 cells at the fine-scale chromatin loop level rather than at the large-scale domain level. Furthermore, our findings underscored the pivotal role of CTCF anchored chromatin interactions in reshaping chromatin architecture during immune responses. Knock-out of the CTCF locus further confirmed that the CTCF anchored enhancers are associated with the activation of immune genes via long-range interactions. Notably, ChIA-PET data also supported the spatial relationship between single nucleotide polymorphisms (SNPs) and the related gene transcription in 3D genome aspect. Our findings in this study provide new clues and potential targets to explore key elements related to diseases in swine and are also likely to shed light on elucidating chromatin organization and dynamics underlying the process of mammalian infectious diseases.

Immune responses and transcription landscape of adults with the third dose of homologous and heterologous booster vaccines of COVID-19.

Background: Heterologous booster vaccines are more effective than homologous booster vaccines in combating the coronavirus disease 2019 (COVID-19) outbreak. However, our understanding of homologous and heterologous booster vaccines for COVID-19 remains limited. Methods: We recruited 34 healthy participants from two cohorts who were primed with two-dose inactivated COVID-19 vaccine before, vaccinated with COVID-19 inactivated vaccine and adenovirus-vectored vaccine (intramuscular and aerosol inhalation of Ad5-nCoV) as a third booster dose. We assessed the immune responses of participants before and 14 days after vaccination, including levels of neutralizing antibodies, IgG, and cytokines, and quantified the transcriptional profile of peripheral blood mononuclear cells (PBMCs). Results: The Ad5-nCoV group showed a significantly higher neutralizing antibody geometric mean titer (GMT) compared to the ICV group after 14 days of heterologous boosting. The intramuscular Ad5-nCoV group had a GMT of 191.8 (95% CI 129.0, 285.1) compared to 38.1 (95% CI 23.1, 62.8) in the ICV1 group (p<0.0001). The aerosolized Ad5-nCoV group had a GMT of 738.4 (95% CI 250.9-2173.0) compared to 244.0 (95% CI 135.0, 441.2) in the ICV2 group (p=0.0434). Participants in the aerosolized Ad5-nCoV group had median IFN-γ+ spot counts of 36.5 (IQR 15.3-58.8) per 106 PBMCs, whereas, both intramuscular Ad5-nCoV and CoronaVac immunization as the third dose showed lower responses. This suggests that a third dose of booster Ad5-nCoV vaccine (especially aerosolized inhalation) as a heterologous vaccine booster induces stronger humoral and cellular immune responses, which may be more potent against VOCs than the use of inactivated vaccine homologs. In transcriptomic analyses, both aerosolized inhalation/intramuscular injection of the Ad5-nCoV vaccine and inactivated vaccine induced a large number of differentially expressed genes that were significantly associated with several important innate immune pathways including inflammatory responses, regulation of the defense response, and regulation of cytokine production. In addition, we identified crucial molecular modules of protective immunity that are significantly correlated with vaccine type and neutralizing antibodies level. Conclusion: This study demonstrated that inhalation/intramuscular injection of the Ad5-nCoV vaccine-mediated stronger humoral and cellular immune responses compared with the inactivated vaccine, and correlated significantly with innate immune function modules, supporting a heterologous booster immunization strategy.

Study on the mechanism of ROS-induced oxidative stress injury and the broad-spectrum antimicrobial performance of nickel ion-doped V6O13 powder.

In this study, pure V6O13 and nickel ion-doped V6O13 powders were synthesized by a simple hydrothermal-calcination method, and their broad-spectrum antimicrobial properties and mechanisms were investigated. The crystal structure, morphology, and chemical state of the powders were thoroughly analyzed by XRD, SEM, TEM, XPS, and UV-Vis. Their antimicrobial properties and mechanisms were evaluated by the ring of inhibition, bio-SEM, live-dead cell staining, ROS detection, and protein leakage experiments. The results showed that nickel ion doping modulated the oxygen defects of V6O13, generating more reactive oxygen species and leading to more severe oxidative stress, resulting in a broad-spectrum and highly efficient antimicrobial effect. This study also revealed the antimicrobial mechanism based on oxygen defect -induced ROS production, which caused cellular oxidative stress damage, leading to leakage of intracellular substances and cell death. This study not only demonstrates the potential of V6O13 as an efficient antimicrobial agent but also provides a strong experimental basis and theoretical support for the engineering design and optimization of novel antimicrobial materials by modulating material defects through ion doping.

Proanthocyanidins alleviate Henoch-Schönlein purpura by mitigating inflammation and oxidative stress through regulation of the TLR4/MyD88/NF-κB pathway.

OBJECTIVE: Investigate Proanthocyanidins (PCs) efficacy and mechanisms in treating Henoch-Schönlein purpura (HSP)-like rat models, focusing on inflammatory and oxidative stress (OS) responses. METHODS: An HSP-like rat model was established using ovalbumin (OVA) injection, leading to symptoms mimicking HSP. The study measured inflammatory markers (IL-4, IL-17, TNF-α), OS markers (MDA, SOD, CAT), and assessed the TLR4/MyD88/NF-κB signaling pathway's involvement via histopathological and immunofluorescence analyses. RESULTS: PCs treatment significantly improved HSP-like symptoms, reduced inflammatory cell infiltration, and decreased IgA deposition in renal mesangial areas. Serum analyses revealed that PCs effectively lowered IL-4, IL-17, TNF-α, and MDA levels while increasing SOD and CAT levels (p < 0.05). Crucially, PCs also downregulated TLR4, MyD88, and NF-κB expressions, highlighting the blockage of the TLR4-mediated signaling pathway as a key mechanism. CONCLUSION: PCs show promising therapeutic effects in HSP-like rats by mitigating inflammatory responses and oxidative damage, primarily through inhibiting the TLR4/MyD88/NF-κB pathway. These findings suggest PCs as a potential treatment avenue for HSP, warranting further investigation.

Genomes of diverse Actinidia species provide insights into cis-regulatory motifs and genes associated with critical traits.

BACKGROUND: Kiwifruit, belonging to the genus Actinidia, represents a unique fruit crop characterized by its modern cultivars being genetically diverse and exhibiting remarkable variations in morphological traits and adaptability to harsh environments. However, the genetic mechanisms underlying such morphological diversity remain largely elusive. RESULTS: We report the high-quality genomes of five Actinidia species, including Actinidia longicarpa, A. macrosperma, A. polygama, A. reticulata, and A. rufa. Through comparative genomics analyses, we identified three whole genome duplication events shared by the Actinidia genus and uncovered rapidly evolving gene families implicated in the development of characteristic kiwifruit traits, including vitamin C (VC) content and fruit hairiness. A range of structural variations were identified, potentially contributing to the phenotypic diversity in kiwifruit. Notably, phylogenomic analyses revealed 76 cis-regulatory elements within the Actinidia genus, predominantly associated with stress responses, metabolic processes, and development. Among these, five motifs did not exhibit similarity to known plant motifs, suggesting the presence of possible novel cis-regulatory elements in kiwifruit. Construction of a pan-genome encompassing the nine Actinidia species facilitated the identification of gene DTZ79_23g14810 specific to species exhibiting extraordinarily high VC content. Expression of DTZ79_23g14810 is significantly correlated with the dynamics of VC concentration, and its overexpression in the transgenic roots of kiwifruit plants resulted in increased VC content. CONCLUSIONS: Collectively, the genomes and pan-genome of diverse Actinidia species not only enhance our understanding of fruit development but also provide a valuable genomic resource for facilitating the genome-based breeding of kiwifruit.

Integration of interpretable machine learning and environmental magnetism elucidates reduction mechanism of bioavailable potentially toxic elements in lakes after monsoon.

Little information is available on the influence of substantial precipitation and particulate matter entering during the monsoon process on the release of potentially toxic elements (PTEs) into lake sediments. Sediments from a typical subtropical lake across three periods, pre-monsoon, monsoon, and post-monsoon, were collected to determine the chemical forms of 12 PTEs (As, Cd, Co, Cr, Cu, Fe, Hg, Pb, Mn, Ni, Sb, and Zn), magnetic properties, and physicochemical indicators. Feature importance, Shapley additive explanations, and partial dependence plots were used to explore the factors influencing bioavailable PTEs. The proportion of bioavailable forms of PTEs decreased from 3.85 % (Cd) to 87.84 % (Hg) after the monsoon. Gradient extreme boosting demonstrated robust fitting accuracy for the prediction of the bioavailable forms of the 12 PTEs (R2 > 0.84). Shapley additive explanations identified that the bioavailable forms were influenced by the total PTE concentrations, wind, shortwave radiation, and particle inputs (25.1 %-88.5 % for total importance), either individually or in combination. The partial dependence plots highlighted the influence thresholds of background values and anthropogenic factors on the bioavailable forms of PTEs. Changes in environmental properties could indicate the process of external sediment influx into lakes. The optimized model combined with magnetic parameters showed strong performance in other cases (coefficient of determination>0.58), confirming the ubiquitous decrease in bioavailable forms of PTEs in sediments across subtropical lakes after monsoons.

Ultrahigh electromechanical response from competing ferroic orders.

Materials with electromechanical coupling are essential for transducers and acoustic devices as reversible converters between mechanical and electrical energy1-6. High electromechanical responses are typically found in materials with strong structural instabilities, conventionally achieved by two strategies-morphotropic phase boundaries7 and nanoscale structural heterogeneity8. Here we demonstrate a different strategy to accomplish ultrahigh electromechanical response by inducing extreme structural instability from competing antiferroelectric and ferroelectric orders. Guided by the phase diagram and theoretical calculations, we designed the coexistence of antiferroelectric orthorhombic and ferroelectric rhombohedral phases in sodium niobate thin films. These films show effective piezoelectric coefficients above 5,000 pm V-1 because of electric-field-induced antiferroelectric-ferroelectric phase transitions. Our results provide a general approach to design and exploit antiferroelectric materials for electromechanical devices.

Effects of adolescent alcohol exposure on oligodendrocyte lineage cells and myelination in mice: Age and subregion differences.

Adolescence is an important phase for the structural and functional development of the brain. The immaturity of adolescent brain development is associated with high susceptibility to exogenous disturbances, including alcohol. In this study, the acquisition of conditioned place preference (CPP) in adolescent mice by alcohol (2 g/kg) and the parvalbumin-positive interneurons (PV+ interneurons), oligodendrocyte lineage cells (OPCs), and myelination in the medial prefrontal cortex (mPFC) were assessed. We aim to determine the age- and subregional-specificity of the effects of alcohol. Alcohol (2 g/kg) was injected intraperitoneally on even days, and saline was injected intraperitoneally on odd days. The control group received a continuous intraperitoneal injection with saline. Differences in alcohol-induced CPP acquisition were assessed, followed by immunohistochemical staining. The results showed a pronounced CPP acquisition in 4- and 5-week-old mice. In the mPFC, there were reduced PV+ interneurons and OPCs in 3-week-old mice and reduced oligodendrocyte numbers in 4-week-old mice. The 5-week-old mice showed impaired myelination and a decrease in the number of PV+ interneurons, mature oligodendrocytes, and OPCs in the mPFC. Since the alterations in 5-week-old mice are more pronounced, we further explored the mPFC-associated subregional-specificity. In the alcohol-exposed mice, the oligodendrocyte numbers were decreased in the anterior cingulate cortex (ACC), PV+ interneuron numbers were declined in the prelimbic cortex (PL), and the number of oligodendrocytes, PV+ interneurons, and OPCs was also decreased with impaired myelination in the infralimbic cortex (IL). Our data suggest that adolescent alcohol exposure notably affected the acquisition of CPP, myelin formation, and the counts of PV+ interneurons, mature oligodendrocytes, and OPCs in the mPFC in 5-week-old mice. Also, the IL subregion was the worst-affected subregion of the mPFC in alcohol-exposed 5-week-old mice. It reveals that the effects of alcohol on adolescence and its mPFC myelination show obvious age- and subregional-specificity.

SLL-1A-16 suppresses proliferation and induces autophagy in non-small-cell lung cancer cells via the AKT/mTOR signaling pathway.

Non-small-cell lung cancer (NSCLC), which accounts for approximately eighty-five percent of lung cancer diagnoses worldwide, is a malignancy with high incidence and mortality rates. Among the various antitumor compounds, organic selenium-containing compounds have emerged as a promising class of therapeutic agents for cancer treatment. In the present study, SLL-1A-16, a new organoselenium small molecule, was discovered to exhibit antiproliferative activity against NSCLC both in vitro and in vivo. Treatment with SLL-1A-16 significantly inhibited NSCLC cell proliferation and induced apoptosis and autophagy. Mechanistically, SLL-1A-16 inhibited cell proliferation through G1-S phase arrest by reducing cyclin D1 and CDK4 expression. Additionally, SLL-1A-16 significantly induced apoptosis by upregulating cleaved caspase 3 and Bax expression, while downregulating Bcl-2 levels. Our study also demonstrated that SLL-1A-16 induced autophagy in NSCLC cells by inhibiting the Akt/mTOR pathway. Overall, our findings suggest that SLL-1A-16 could induce cell cycle arrest, apoptosis and autophagy in NSCLC cells by inhibiting the Akt/mTOR signaling pathways, providing a theoretical basis for the potential clinical application of SLL-1A-16 as a chemotherapeutic agent in NSCLC treatment.

Growth of sulfur-doped bismuth oxybromide nanosheets on carbon fiber cloth for photocatalytically purifying antibiotic wastewater.

Bismuth oxybromide (BiOBr) nanomaterials are well-known efficient powder-shaped photocatalyst for degrading antibiotic wastewater, but their practical applications have been limited by unsatisfactory photo-absorption, weak photocatalytic activity and poor recyclability. To address these issues, we demonstrate that the growing of S-doped BiOBr nanosheets on carbon fiber cloth (CFC) can lead to efficient photocatalysis with recyclable features. With carbon fiber cloth as the substrate, S-doped BiOBr (BiOBr-Sx) nanosheets (diameter: ∼500 nm, thicknesses: ∼5-90 nm) was prepared by solvothermal method with thiourea as dopant. With the increase of thiourea (0-0.2 g) in the precursor solution, BiOBr-Sx nanosheets exhibit a significant shift in the photo-absorption edge from 420 to 461 nm and decreased thicknesses from 90 to 5 nm, accompanying by the increased proportion of (010) exposed surface. Amony them, CFC/BiOBr-S0.5 can degrade various contaminants (such as 98.7 % levofloxacin (LVFX), 95.6 % ciprofloxacin (CIP) and 95.9 % tetracycline (TC)) with most degradation efficiency within 120 min of visible light irradiation, which are 1.6, 1.9 and 1.4 times than that of CFC/BiOBr (61.4 % LVFX, 49.5 % CIP and 67.1 % TC), respectively. Significantly, when CFC/BiOBr-S0.05 photocatalytic fabric is combined with a multi-stage flow device to treat the flowing wastewater (10 mg/L LVFX, rate: 1 L/h), 91.0 % LVFX can be degraded after tenth grade. Therefore, this study not only demonstrates the controllable preparation of S-doped BiOBr nanosheets with different thickness on CFC but also highlights the practical applications of fabric-based photocatalysts for purifying the flowing sewage efficiently.

Photocatalytic production of a C12 liquid biofuel precursor and H2 by Ni(OH)2-ZnIn2S4 in anaerobic water.

Herein, we presented a bifunctional photocatalytic system for 5-hydroxymethylfurfural (HMF) valorization over Ni(OH)2-modified ZnIn2S4. Instead of forming 2,5-diformylfuran C6 products from conventional HMF aerobic oxidation, C-C coupling C12 products and H2 were produced in anaerobic water, which can be an important liquid fuel intermediate and gaseous energy carrier, respectively. This work could spark more insight for biomass utilization.

Distribution rules of 8-mer spectra and characterization of evolution state in animal genome sequences.

BACKGROUND: Studying the composition rules and evolution mechanisms of genome sequences are core issues in the post-genomic era, and k-mer spectrum analysis of genome sequences is an effective means to solve this problem. RESULT: We divided total 8-mers of genome sequences into 16 kinds of XY-type due to XY dinucleotides number in 8-mers. Previous works explored that the independent unimodal distributions observed only in three CG-type 8-mer spectra, while non-CG type 8-mer spectra have not the universal phenomenon from prokaryotes to eukaryotes. On this basis, we analyzed the distribution variation of non-CG type 8-mer spectra across 889 animal genome sequences. Following the evolutionary order of animals from primitive to more complex, we found that the spectrum distributions gradually transition from unimodal to tri-modal. The relative distance from the average frequency of each non-CG type 8-mers to the center frequency is different within a species and among different species. For the 8-mers contain CG dinucleotides, we further divided these into 16 subsets, where each 8-mer contains both CG and XY dinucleotides, called XY1_CG1 subsets. We found that the separability values of XY1_CG1 spectra are closely related to the evolution and specificity of animals. Considering the constraint of Chargaff's second parity rule, we finally obtained 10 separability values as the feature set to characterize the evolution state of genome sequences. In order to verify the rationality of the feature set, we used 14 common classification algorithms to perform binary classification tests. The results showed that the accuracy (Acc) ranged between 98.70% and 83.88% among birds, other vertebrates and mammals. CONCLUSION: We proposed a credible feature set to characterizes the evolution state of genomes and obtained satisfied results by the feature set on large scale classification of animals.

Torque Teno Sus Virus 1: A Potential Surrogate Pathogen to Study Pig-Transmitted Transboundary Animal Diseases.

Understanding the epidemiology and transmission dynamics of transboundary animal diseases (TADs) among wild pigs (Sus scrofa) will aid in preventing the introduction or containment of TADs among wild populations. Given the challenges associated with studying TADs in free-ranging populations, a surrogate pathogen system may predict how pathogens may circulate and be maintained within wild free-ranging swine populations, how they may spill over into domestic populations, and how management actions may impact transmission. We assessed the suitability of Torque teno sus virus 1 (TTSuV1) to serve as a surrogate pathogen for molecular epidemiological studies in wild pigs by investigating the prevalence, persistence, correlation with host health status and genetic variability at two study areas: Archbold's Buck Island Ranch in Florida and Savannah River Site in South Carolina. We then conducted a molecular epidemiological case study within Archbold's Buck Island Ranch site to determine how analysis of this pathogen could inform transmission dynamics of a directly transmitted virus. Prevalence was high in both study areas (40%, n = 190), and phylogenetic analyses revealed high levels of genetic variability within and between study areas. Our case study showed that pairwise host relatedness and geographic distance were highly correlated to pairwise viral genetic similarity. Molecular epidemiological analyses revealed a distinct pattern of direct transmission from pig to pig occurring within and between family groups. Our results suggest that TTSuV1 is highly suitable for molecular epidemiological analyses and will be useful for future studies of transmission dynamics in wild free-ranging pigs.

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.

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.

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.

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.

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.