Deletion of protein kinase C θ attenuates hepatic ischemia/reperfusion injury and further elucidates its mechanism in pathophysiology.

Objectives: Hepatic ischemia-reperfusion (HIR) is a severe process in pathophysiology that occurs clinically in hepatectomy, and hepatic transplantations. The present study aimed to investigate the effect of PKC θ deletion against HIR injury and elucidate its mechanism in pathophysiology. Materials and Methods: HIR injury was induced in wild-type and PKC θ deletion mice treated with or without heme. The ALT and AST levels were determined to evaluate liver function. HIR injury was observed via histological examination. Oxidative stress and inflammatory response markers, and their signaling pathways were detected. Results: The study found that PKC θ knockout decreased serum AST and ALT levels when compared to the WT mice. Furthermore, heme treatment significantly reduced the ALT and AST levels of the PKC θ deletion mice compared with the untreated PKC θ deletion mice. PKC θ deletion markedly elevated superoxide dismutase activity in the liver tissue, reduced malondialdehyde content in the tissue, and the serum TNF-α and IL-6 levels compared with the WT mice. Heme treatment was observed to elevate the activity of SOD and reduced MDA content and serum of TNF-α and IL 6 in the PKC θ deletion animals. Meanwhile, heme treatment increased HO-1 and Nrf 2 protein expression, and reduced the levels of TLR4, phosphorylated NF-κB, and IKB-α. Conclusion: These findings suggested that PKC θ deletion ameliorates HIR, and heme treatment further improves HIR, which is related to regulation of PKC θ deletion on Nrf 2/HO-1 and TLR4/NF-κB/IKB α pathway.

Assessing Hepatotoxicity in Novel and Standard Short Regimens for Rifampicin-Resistant Tuberculosis: Insights from the TB-TRUST and TB-TRUST -plus Trials.

BACKGROUND: Efforts to shorten rifampicin-resistant tuberculosis (RR-TB) treatment have led to concerns about hepatotoxicity in shorter regimens. We evaluated hepatotoxicity in two novel regimens against the standard shorter regimen recommended by WHO. METHODS: Participants from the TB-TRUST and TB-TRUST plus trials were assigned to the WHO shorter regimen, a levofloxacin-based regimen, or a bedaquiline-based regimen. Liver function was tested bi-weekly in the first month, then monthly until treatment ended. Eligibility required receiving at least one drug dose and undergoing at least two liver function tests. RESULTS: Of 429 patients, hepatotoxicity was most prevalent in the WHO shorter group (26.7% of 169), compared to 4.7% in the levofloxacin group (172 patients), and 5.7% in the bedaquiline group (88 patients). The median peak ALT levels were 1.67 × ULN for WHO, 0.82 × ULN for levofloxacin, and 0.88 × ULN for bedaquiline groups. The incidence of drug-induced liver injury was significantly higher in the WHO group (18.3%) than in the levofloxacin (3.5%) and bedaquiline (4.6%) groups. Time to significant ALT elevation was about 2.8 months, with no differences between groups. CONCLUSIONS: Two novel regimens demonstrated lower hepatotoxicity compared to the WHO shorter regimen. Entire course management monitoring is recommended in RR-TB treatment.

The occurrence of banana Fusarium wilt aggravates antibiotic resistance genes dissemination in soil.

The spread of antibiotic resistance genes (ARGs) and subsequent soil-borne disease outbreaks are major threats to soil health and sustainable crop production. However, the relationship between occurrences of soil-borne diseases and the transmission of soil ARGs remains unclear. Here, soil ARGs, mobile genetic elements and microbial communities from co-located disease suppressive and conducive banana orchards were deciphered using metagenomics and metatranscriptomics approaches. In total, 23 ARG types, with 399 subtypes, were detected using a metagenomics approach, whereas 23 ARG types, with 452 subtypes, were discovered using a metatranscriptomics method. Furthermore, the metagenomics analysis revealed that the ARG total abundance levels were greater in rhizospheres (0.45 ARGs/16S rRNA on average) compared with bulk (0.32 ARGs/16S rRNA on average) soils. Interestingly, metatranscriptomics revealed that the total ARG abundances were greater in disease-conducive (8.85 ARGs/16S rRNA on average) soils than disease suppressive (1.45 ARGs/16S rRNA on average) soils. Mobile genetic elements showed the same trends as ARGs. Network and binning analyses indicated that Mycobacterium, Streptomyces, and Blastomonas are the main potential hosts of ARGs. Furthermore, Bacillus was significantly and negatively correlated with Fusarium (P < 0.05, r = -0.84) and hosts of ARGs (i.e., Mycobacterium, Streptomyces, and Blastomonas). By comparing metagenomic and metatranscriptomic analyses，this study demonstrated that metatranscriptomics may be more sensitive in indicating ARGs activities in soil. Our findings enable the more accurate assessment of the transmission risk of ARGs. The data provide a new perspective for recognizing soil health, in which soil-borne disease outbreaks appear to be associated with ARG spread, whereas beneficial microbe enrichment may mitigate wilt disease and ARG transmission.

Sesquiterpenoids from the roots and rhizomes of Valeriana officinalis var. latifolia.

The genus Valeriana is used in traditional Chinese medicine to treat nervous disorders, sleep disorders, epilepsy and skin diseases. A large number of sesquiterpenoids from this genus have been found to exhibit anti-inflammatory, antiproliferative, anti-influenza virus and neuroprotective activities. In order to discover more sesquiterpenoids with structural diversity and bioactivity from Valeriana plants, fifteen sesquiterpenoids, including ten undescribed ones, valernaenes A-J (1, 5-7, 9-11 and 13-15), were isolated from the roots and rhizomes of Valeriana officinalis var. latifolia. Their structures were elucidated by extensive spectroscopic techniques (1D, 2D NMR and HRESIMS) and electronic circular dichroism (ECD) calculation. Structurally, valernaenes C (6) and D (7) were two caryophyllane-type norsesquiterpenoids. In addition, valernaenes A (1) and F (10) exhibited anti-influenza virus activity with EC50 values of 38.76 ± 1.44 and 23.01 ± 4.89 µM, respectively. Furthermore, caryophyllenol A (2) showed promoting effect on nerve growth factor (NGF)-mediated neurite outgrowth in PC12 cells with differentiation rate of 12.26% at a concentration of 10 µM. This study not only enriched the structural diversity of sesquiterpenoids in the genus Valeriana, but also provided theoretical basis for the discovery of anti-influenza virus and neuroprotective agents from this genus.

Roles and mechanisms of fucoidan against dermatitis: A review.

Fucoidan is a sulfate-containing polysaccharide derived from the cell walls of brown algae and marine invertebrates. Fucoidan is widely used for the treatment of various diseases owing to its various biological activities. Dermatitis is an inflammatory reaction that affects the skin. The primary clinical manifestations include atopic dermatitis (AD or eczema) and various subtypes of contact dermatitis. The treatment of dermatitis primarily improves symptoms and reduces inflammation. However, owing to individual variations, some patients have a poor prognosis or symptom recurrence after conventional treatment. Owing to the excellent anti-allergic and anti-inflammatory activities of the low cost nature compound fucoidan, its therapeutic effect in inflammatory diseases has recently attracted the attention of researchers. This article summarizes and analyzes the advantages and pharmacological mechanisms of fucoidan against dermatitis to provide a reference for the selection of drugs for the treatment of dermatitis.

Exploration on cold adaptation of Antarctic lichen via detection of positive selection genes.

Lichen as mutualistic symbiosis is the dominant organism in various extreme terrestrial environment on Earth, however, the mechanisms of their adaptation to extreme habitats have not been fully elucidated. In this study, we chose the Antarctic dominant lichen species Usnea aurantiacoatra to generate a high-quality genome, carried out phylogenetic analysis using maximum likelihood and identify genes under positive selection. We performed functional enrichment analysis on the positively selected genes (PSGs) and found that most of the PSGs focused on transmembrane transporter activity and vacuole components. This suggest that the genes related to energy storage and transport in Antarctic U. aurantiacoatra were affected by environmental pressure. Inside of the 86 PSGs screened, two protein interaction networks were identified, which were RNA helicase related proteins and regulator of G-protein signaling related proteins. The regulator of the G-protein signaling gene (UaRGS1) was chosen to perform further verification by the lichen genetic manipulation system Umbilicaria muhlenbergii. Given that the absence of UmRgs1 resulted in elevated lethality to cold shock, the role for UaRgs1 in Antarctic U. aurantiacoatra resistance to cold can be inferred. The investigation of lichen adaptation to extreme environments at the molecular level will be opened up.

Supplementation of Ampelopsis grossedentata extract contributes to the improvement of intestinal health in swine.

Introduction: Ampelopsis grossedentata (vine tea), a high polyphenol content antioxidant plant resource, is renowned for its medicinal benefits. This study aimed to investigate the effects of Ampelopsis grossedentata extract (AGE) on anti-inflammatory and antioxidant ability, enhancement of intestinal immunity, improvement of intestinal structure, and regulation of gut microbiota in swine. Methods: A total of 135 weaned piglets were randomly divided into three groups: a control group, a low-dose group, and a high-dose group. Pigs were weighed and blood was collected on days 36, 85, and 154. The feed intake was recorded daily to calculate growth performance parameters. On day 154, five to six pigs in each group were randomly selected and euthanized to obtain a small intestine to investigate the effects of AGE on anti-inflammatory and antioxidant abilities and gut microbiota. Results: The results showed that 500 mg/kg AGE increased the expression of anti-inflammatory and immune cytokines (IL-10, IgG, and IgA) (p < 0.05, p < 0.01) and decreased the expression of proinflammatory cytokines (IL-1ß) (p < 0.05) in serum. Additionally, 500 mg/kg AGE enhanced the antioxidant capacity by increasing the GSH-Px, CAT, and SOD (p < 0.05, p < 0.01). Discussion: A total of 500 mg/kg AGE significantly increased the abundance of gut microbiota, enhanced the gut barrier, and modulated gut immunity. During the piglet phase, 500 mg/kg AGE increased the relative abundance of Prevotella (p < 0.05). During the growing-finishing phase, 500 mg/kg AGE increased the relative abundance of unclassified_f__Lachnospiraceae and Bacteroides (p < 0.05, p < 0.01). Overall, we recommended 500 mg/kg AGE as a routine addition dose for swine to improve porcine growth performance and intestinal health.

Treatment outcomes of infertile women with endometrial hyperplasia undergoing their first IVF/ICSI cycle: A matched-pair study.

OBJECTIVE: The aim was to analyze the clinical characteristics, controlled ovarian stimulation status, pregnancy outcomes, and major factors influencing live births in patients with endometrial hyperplasia (EH) undergoing IVF/ICSI for assisted reproduction, so as to identify potential intervention measures. STUDY DESIGN: Patients with EH who achieved complete remission (CR) after conservative treatment and who were undergoing their first IVF/ICSI cycle were included in this matched-pair study. Patients with normal endometriums were matched at a 1:2 ratio with the control group for the first cycle of controlled ovarian stimulation. Matching was based on age, and reproductive outcomes were analyzed. RESULTS: Among the 263 patients (including 51 cases with atypical endometrial hyperplasia) in the study group, the pregnancy rate after the first controlled ovarian stimulation cycle was 48.67 % (128/263), and the live birth rate was 34.98 % (92/263). Multiple logistic regression analysis revealed that maternal age, body mass index (BMI), and endometrial thickness were significantly associated with live births (P<0.001). Specifically, being aged ≥ 35 years (OR 0.450, 95 % CI 0.223-0.907) and having a BMI≥28 kg/m2 (OR 0.358, 95 % CI 0.161-0.798) were identified as unfavorable factors for a clinical live birth, while an endometrial thickness ≥ 10 mm was found to be a favorable factor. CONCLUSION(S): ART is effective in patients with EH who have achieved CR after conservative treatment. Avoiding unnecessary intrauterine procedures, controlling body weight appropriately, and choosing suitable ART methods as soon as possible may be beneficial for clinical outcomes.

Spatial and temporal dynamics of microbes and genes in drinking water reservoirs: Distribution and potential for taste and odor generation.

Numerous reservoirs encounter challenges related to taste and odor issues, often attributed to odorous compounds such as geosmin (GSM) and 2-methylisoborneol (2-MIB). In this study, two large reservoirs located in northern and southern China were investigated. The Jinpen (JP) reservoir had 45.99 % Actinomycetes and 14.82 % Cyanobacteria, while the Xikeng (XK) reservoir contained 37.55 % Actinomycetes and 48.27 % Cyanobacteria. Most of the 2-MIB produced in surface layers of the two reservoirs in summer originated from Cyanobacteria, most of the 2-MIB produced in winter and in the bottom water originated from Actinomycetes. Mic gene abundance in the XK reservoir reached 5.42 × 104 copies/L in winter. The abundance of GSM synthase was notably high in the bottom layer and sediment of both reservoirs, while 2-MIB synthase was abundant in the surface layer of the XK reservoir, echoing the patterns observed in mic gene abundance. The abundance of odor-producing enzymes in the two reservoirs was inhibited by total nitrogen, temperature significantly influenced Actinomycetes abundance in the JP reservoir, whereas dissolved oxygen had a greater impact in the XK reservoir. Overall, this study elucidates the molecular mechanisms underlying odor compounding, providing essential guidance for water quality management strategies and the improvement of urban water reservoir quality.

HLA A*24:02-restricted T cell receptors cross-recognize bacterial and preproinsulin peptides in type 1 diabetes.

CD8+ T cells destroy insulin-producing pancreatic ß cells in type 1 diabetes through HLA class I-restricted presentation of self-antigens. Combinatorial peptide library screening was used to produce a preferred peptide recognition landscape for a patient-derived T cell receptor (TCR) that recognized the preproinsulin-derived (PPI-derived) peptide sequence LWMRLLPLL in the context of disease risk allele HLA A*24:02. Data were used to generate a strong superagonist peptide, enabling production of an autoimmune HLA A*24:02-peptide-TCR structure by crystal seeding. TCR binding to the PPI epitope was strongly focused on peptide residues Arg4 and Leu5, with more flexibility at other positions, allowing the TCR to strongly engage many peptides derived from pathogenic bacteria. We confirmed an epitope from Klebsiella that was recognized by PPI-reactive T cells from 3 of 3 HLA A*24:02+ patients. Remarkably, the same epitope selected T cells from 7 of 8 HLA A*24+ healthy donors that cross-reacted with PPI, leading to recognition and killing of HLA A*24:02+ cells expressing PPI. These data provide a mechanism by which molecular mimicry between pathogen and self-antigens could have resulted in the breaking of self-tolerance to initiate disease.

Macular vascular density alteration patterns in paediatric optic neuritis patients with serum MOG antibody positivity detected by optic coherence tomography angiography.

PURPOSE: The retinal microvascular network plays a crucial role in inflammatory injury in paediatric optic neuritis (PON) with serum MOG antibody positivity (MOG + PON). This study compared retinal microvascular densities and structural alterations in MOG + PON eyes with paediatric isolated optic neuritis (PION) eyes and followed up with the final best-corrected visual acuity (BCVA) after 6 months. METHODS: A total of 29 children (52 eyes) with PON, including 15 MOG + PON cases (28 eyes), 6 PION cases (10 eyes), 2 neuromyelitis optica spectrum disorders associated PON(NMOSD-PON) cases (4 eyes), 6 MOG-associated disease (MOGAD) patients without ON-affected eyes (MOG + NPON) cases (10 eyes) and age- and gender-matched healthy controls (HCs) underwent superficial/deep retinal angiography density (SAD/DAD) by optical coherence tomography angiography (OCTA). Their BCVAs were followed up until 6 months after PON onsets. RESULTS: MOG + PON cases had better final BCVAs than PION and NMOSD-ON. MOG + PON (35.7 ± 10.3 %) and PION (40.1 ± 10.3 %) eyes experienced severe SAD reductions in contrast to MOGAD+NPON (48.7 ± 5.2 %) and HCs eyes (55.6 ± 8.2 %). However, DAD in MOG + PON eyes (48.5 ± 9.2 %) and MOG + NPON eyes (53.1 ± 3.3 %) increased compared to HC eyes (45.7 ± 9.6 %; p = 0.028 and 0.009, respectively). SAD reduction occurred in acute PON and was detected as early as 2 weeks after PON onset. CONCLUSIONS: MOG + PON eyes had better final BCVAs than PION eyes, which displayed superficial retinal microvascular perfusion reductions and deep microvascular perfusion increases. SAD could be a sensitive surrogate for PON attacks in children with MOGAD.

Fei-Yan-Qing-Hua decoction exerts an anti-inflammatory role during influenza by inhibiting the infiltration of macrophages and neutrophils through NF-κB and p38 MAPK pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Fei-Yan-Qing-Hua decoction (FYQHD) is an empirical formula that has shown clinical success in treating community-acquired pneumonia (CAP) for two decades. Influenza viral infection is a significant trigger for severe pneumonia, yet the role of FYQHD in treating influenza remains unclear. AIM OF THE STUDY: This study aimed to assess the potential efficacy of FYQHD in treating influenza viral infection and to elucidate its underlying mechanisms. MATERIALS AND METHODS: The protective effects of FYQHD against influenza were evaluated through survival assessments and pathological analyses. Transcriptomic analysis was performed to identify the genes and pathways influenced by FYQHD in influenza. The anti-inflammatory effects and molecular mechanisms of FYQHD were studied in macrophages stimulated by Toll-like receptor (TLR) 7 ligation in vitro. The key constituents of FYQHD absorbed in mouse sera were identified using untargeted metabolomics, and the anti-inflammatory activity of some of these compounds in macrophages was evaluated using ELISA. RESULTS: Our findings demonstrate that FYQHD enhances survival and reduces lung damage in PR8-infected mice, primarily through its anti-inflammatory properties. Lung indexes and organ damage were significantly lower in the PR8 + OSV + FYQHD group compared to the PR8 + OSV group, indicating a potential complementary therapeutic effect of FYQHD and OSV in treating influenza. FYQHD effectively reduced chemokine expression, thereby decreasing the chemotaxis and infiltration of inflammatory monocytes/macrophages and neutrophils in the lungs. The anti-inflammatory effects of FYQHD in macrophages were achieved through the inhibition of NF-κB activation and p38 phosphorylation. The key constituents of FYQHD absorbed in mouse sera were identified, with some, such as wogonin, luteolin, kaempferol, and isorhamnetin, showing anti-inflammatory effects in primary macrophages. CONCLUSION: FYQHD demonstrates protective efficacy against influenza and shows promise as an adjuvant therapeutic agent, particularly when used in combination with antiviral drugs like OSV. The potent anti-inflammatory components within FYQHD provide a basis for further exploration in drug research and development aimed at combating influenza.

Prevalence and disparities in sexual and reproductive health of women of reproductive age (20-49 years) in China: A national cross-sectional study.

Background: Ensuring women's sexual and reproductive health (SRH) is a fundamental human right and key to 2030 agenda of the UN Sustainable Development Goals (SDGs), yet limited evidence exists on SRH in China, including national estimates and disparities of women's SRH experiences, gynaecological diseases, and sexually transmitted diseases (STDs). Methods: A national cross-sectional survey based on a multistage stratified sampling from 15 provinces of China was performed from May 2019 to April 2021. A total of 12 815 reproductive-aged (20-49 years) women were involved. The SRH experiences (including age at menarche, age at first sexual activity, history of abortion, miscarriage, recurrent miscarriage, stillbirth, age at first delivery, types of delivery), the history of gynaecological diseases and STDs, as well as the environmental factors of participants were investigated. Human development index (HDI) was utilised to categorise and describe the socioeconomic status of the regions. The prevalence rates of diseases were compared among different HDI regions. Results: We observed a decrease in the mean age at menarche, an increase in the proportion of women who became sexually active before 20, and a modest rise in mean age at first childbirth across generations. Age-standardised prevalence estimates of miscarriage, recurrent miscarriage, artificial abortion, ectopic pregnancy, and stillbirth were 9.3, 1.4, 55.7, 3.3, and 2.1%, respectively. Approximately 50% of participants reported a history of gynaecological diseases, with vulvovaginitis, cervicitis, and pelvic infection diseases being the most prevalent. The overall prevalence of STDs was estimated at 22.2‰, with mycoplasma genitalium infection having the highest reported prevalence. Disease prevalence varies across HDI regions. Conclusions: Women's SRH behaviours and experiences have evolved, along with shifts in the spectrums of gynaecological diseases and STDs in China. Urgent recalibration of health care policies and disease control strategies is necessary, aligning them with women's changing SRH needs, ultimately ensuring their reproductive health and rights.

SNAI2 as a Prognostic Biomarker Based on Cancer-Associated Fibroblasts in Patients With Lung Adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is a common type of malignant tumor with therapeutic challenges. Cancer-associated fibroblasts (CAFs) promote LUAD growth and metastasis, regulate the tumor immune response, and influence tumor treatment responses and drug resistance. However, the molecular mechanisms through which CAFs control LUAD progression are largely unknown. In this study, we aimed to determine the correlations between CAF-related genes and overall survival (OS) in patients with LUAD. Methods: We acquired the gene expression data and clinical information of 522 patients with LUAD patients from The Cancer Genome Atlas (TCGA) and 442 patients with LUAD from the Gene Expression Omnibus (GEO) databases. CAF infiltration levels were assessed using the Microenvironment Cell Population (MCP) counter, the Estimating the Proportions of Immune and Cancer cells (EPIC) algorithm, and Tumor Immune Dysfunction and Exclusion (TIDE) scores. A CAF-related gene network was constructed using the Weighted gene co-expression network analysis (WGCNA). Based on the CAF-related genes, univariate Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analyses were performed to identify prognostic genes. Gene expression levels within the prognostic model were validated using the Cancer Cell Line Encyclopedia (CCLE) databases and Western blotting. Results: Our results demonstrated that high CAF scores were associated with lower survival rates in patients with LUAD. Gene modules that were highly correlated with high CAF scores were closely associated with tissue characteristics and extracellular matrix structures in LUAD. In addition, correlations between CAF scores and responses to immunotherapy and chemotherapy were observed. Finally, we found that SNAI2 expression was higher in lung cancer tissues than in normal tissues. Conclusion: Deepening our understanding of the influence of CAFs on tumor progression and treatment response at the molecular level can aid the development of more effective therapeutic strategies. This study provides important insights into the functional mechanisms of action of CAFs in LUAD and highlights their clinical implications.

Highly Sensitive Dual-Mode Touch Sensing Device Using Poly(vinylidene fluoride)/Graphene Nitride for Wearable E-Skin: Patterning, High-Temperature Annealing, and Remote Data Transmission.

In recent years, significant advancements in printed electronics and flexible materials have catalyzed the development of electronic skins for wearable applications. However, the low glass transition temperature of flexible substrates poses a challenge as it is incompatible with the high-temperature annealing required for electrode fabrication, thereby limiting the performance of flexible electronic devices. In this study, we address these limitations by proposing a novel flexible device manufacturing process that combines adhesive printing patterning with a transfer printing technology. By employing poly(vinylidene fluoride) (PVDF)/graphene nitride (GCN) as the transfer substrate and dielectric layer, we successfully fabricated a high-performance dual-mode touch sensor on a large scale. The successful development of this dual-mode sensor can be attributed to two key factors: the construction of a robust hydrogen-bonding network between the PVDF/GCN dielectric layer and the carbon electrode and the ability of GCN to restrict the movement of PVDF molecular chains within the dielectric layer. This restriction reduces the overall polarization of the film, enabling the formation of a complete device structure with a highly sensitive edge electric field. The noncontact sensors developed in this study are fully printable into sensor arrays and can be seamlessly integrated with internet of things technology for wearable applications. These sensors exhibit exceptional tactile response and facilitate effective human-machine interactions over extended distances, underscoring their significant potential in fields such as healthcare and artificial intelligence.

Rejuvenation of aged oocyte through exposure to young follicular microenvironment.

Reproductive aging is a major cause of fertility decline, attributed to decreased oocyte quantity and developmental potential. A possible cause is aging of the surrounding follicular somatic cells that support oocyte growth and development by providing nutrients and regulatory factors. Here, by creating chimeric follicles, whereby an oocyte from one follicle was transplanted into and cultured within another follicle whose native oocyte was removed, we show that young oocytes cultured in aged follicles exhibited impeded meiotic maturation and developmental potential, whereas aged oocytes cultured within young follicles were significantly improved in rates of maturation, blastocyst formation and live birth after in vitro fertilization and embryo implantation. This rejuvenation of aged oocytes was associated with enhanced interaction with somatic cells, transcriptomic and metabolomic remodeling, improved mitochondrial function and higher fidelity of meiotic chromosome segregation. These findings provide the basis for a future follicular somatic cell-based therapy to treat female infertility.

LINC00618 facilitates growth and metastasis of hepatocellular carcinoma via elevating cholesterol synthesis by promoting NSUN2-mediated SREBP2 m5C modification.

Dysregulation of cholesterol metabolism is an important feature of cancer development. There are limited reports on the involvement of lncRNAs in hepatocellular carcinoma (HCC) progression via the cholesterol metabolism pathway. The present study explored the effect of LINC00618 on HCC growth and metastasis, and elucidated the underlying mechanisms involved in cholesterol metabolism. Here, we found that LINC00618 expression was upregulated in cancerous tissues from 30 patients with HCC compared to that in adjacent normal tissues. High expression of LINC00618 was detected in metastatic HCC tissues. LINC00618 is predominantly localized in the nucleus and overexpression of LINC00618 facilitated HCC cell proliferation, migration and EMT progression by promoting cholesterol biosynthesis. Mechanistically, the 1-101nt region of LINC00618 bound to NSUN2. LINC00618 inhibited ubiquitin-proteasome pathway-induced NSUN2 degradation. NSUN2 stabilized by LINC00618 increased m5C modification of SREBP2 and promoted SREBP2 mRNA stability in a YBX1-dependent manner, thereby promoting cholesterol biosynthesis in HCC cells. Moreover, mouse HCC xenograft and lung metastasis models were established by subcutaneous and tail vein injections of MHCC97 cells transfected with or without sh-LINC00618. Silencing LINC00618 impeded HCC growth and metastasis. In conclusion, LINC00618 promoted HCC growth and metastasis by elevating cholesterol synthesis by stabilizing NSUN2 to enhance SREBP2 mRNA stability in an m5C-dependent manner.

Anti-infective Properties of Mung Bean (Vigna Radiata (L.)R. Wilczek) Coat Extract on Pseudomonas aeruginosa-Infected Caenorhabditis elegans: Transcriptomics and Pathway Analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Mung bean coat has long been known for its wide-ranging health benefits, including antibacterial, anti-inflammatory, and immune-modulatory properties. For many years in China, mung beans have been employed in the therapeutic management of inflammation induced by pathogenic bacteria infection, yet the precise underlying protective mechanisms remain to be comprehensively elucidated. AIM OF THE STUDY: Given the growing concern over antibiotic resistance, there is a necessity to explore new anti-infective agents. Here, the anti-infective properties of Mung bean coat extract (MBCE) were investigated using a model of Pseudomonas aeruginosa-infected nematodes. MATERIALS AND METHODS: The protective effects of MBCE on Pseudomonas aeruginosa (PA14) infected nematodes were assessed by lifespan assay, reactive oxygen species (ROS) levels, transcriptomics, and Quantitative real-time PCR (qRT-PCR). RESULTS: MBCE significantly improved the survival rates and reduced ROS levels in infected worms. Transcriptomic profiling disclosed predominant KEGG pathway enrichments in immune responses, energy metabolism processes such as oxidative phosphorylation and the tricarboxylic acid cycle, alongside aging-related neurodegenerative diseases and longevity regulatory pathways like PI3K-AKT, MAPK, mTOR, and FOXO. qRT-PCR validation showed that MBCE upregulated antimicrobial peptides (spp-3, lys-1, lys-7, abf-2, cnc-2, nlp-33, clec-85), gram-negative responses (irg-3, src-2, grd-3, col-179), and mitochondrial function (mev-1) gene expressions, while downregulated insulin signaling-related (age-1, akt-1, akt-2, daf-15) gene expressions. Mutant strains lifespan analysis indicated that the nsy-1, sek-1, pmk-1, daf-2, aak-2, sir-2.1, and skn-1 were necessary for lifespan extension mediated by MBCE under PA14 infection, but not clk-1, isp-1, mev-1, or daf-16. CONCLUSION: Collectively, our findings suggested that MBCE increased the survival rates of PA14-infected worms by activating downstream antimicrobial and antioxidant gene expressions through modulation of MAPK, daf-2, aak-2, sir-2.1, and skn-1 pathways. The research underscored the potential of natural plant compounds to strengthen the body's defenses against infections, potentially mitigating harmful ROS levels and improving survival. Additionally, these findings elucidated the mechanisms by which these plant-derived compounds enhance the immune system, implying their potential utility as dietary supplements or as an alternative to conventional antibiotics.

A Novel Asymmetric Diffusion Path for Superior Ion Dynamic in High-Voltage Mg-Based Hybrid Batteries.

Magnesium-based batteries have garnered significant attention due to their high energy density, excellent intrinsic safety, and low cost. However, the application process has been hindered by the high Mg2+ ions diffusion barrier in solid-state structures and solid-liquid interphase. To address this issue, a hybrid battery technology based on Mg anode and Fe-based Prussian Blue Analogue cathode doped with functional transition metal ions and N═O bonds is proposed. Combined multiscale experimental characterizations with theoretical calculations, the subtle lattice distortion can create an asymmetric diffusion path for the active ions, which enables reversible extraction with significantly reduced diffusion barriers achieved by synergistic doping. The optimized cathode exhibits a working potential of 2.3 V and an initial discharge capacity of 152 mAh g-1 at 50 mA g-1. With the preferred electrolyte combined with equivalent concentration [Mg2(µ-Cl)2(DME)4][AlCl4]2 and NaTFSI salt solution, the hybrid system demonstrates superior cycling performance over 200 cycles at a high current density of 200 mA g-1, maintaining ≈100% coulombic efficiency with superior ion dynamic. The findings are expected to be marked an important step in the further application of high-voltage cathodes for Mg-based hybrid batteries.