Rhizobia-diatom symbiosis fixes missing nitrogen in the ocean.

Nitrogen (N2) fixation in oligotrophic surface waters is the main source of new nitrogen (N) to the ocean1 and plays a key role in fueling the biological carbon pump2. Oceanic N2 fixation is almost exclusively attributed to cyanobacteria, even though genes encoding nitrogenase, the enzyme fixing N2 into ammonia, are widespread among marine bacteria and archaea3-5. Little is known about these non-cyanobacterial N2-fixers and direct proof that they can fix N in the ocean is missing. Here we report the discovery of a non-cyanobacterial N2-fixing symbiont, Candidatus Tectiglobus diatomicola, which provides its diatom host with fixed-N in return for photosynthetic carbon. The N2-fixing symbiont belongs to the order Rhizobiales and its association with a unicellular diatom expands the known hosts for this order beyond the well-known N2-fixing rhizobia-legume symbioses on land6. Our results show that the rhizobia-diatom symbiosis can contribute as much fixed-N as cyanobacterial N2-fixers in the tropical North Atlantic, and that they may be responsible for N2 fixation in the vast regions of the ocean where cyanobacteria are too rare to account for the measured rates.

Long-neglected contribution of nitrification to N2O emissions in the Yellow River.

Rivers play a significant role in the global nitrous oxide (N2O) budget. However, the microbial sources and sinks of N2O in river systems are not well understood or quantified, resulting in the prolonged neglect of nitrification. This study investigated the isotopic signatures of N2O, thereby quantifying the microbial source of N2O production and the degree of N2O reduction in the Yellow River. Although denitrification has long been considered to be the dominant pathway of N2O production in rivers, our findings indicated that denitrification only accounted for 18.3% (8.2%-43.0%) of the total contribution to N2O production in the Yellow River, with 50.2%-80.2% being concurrently reduced. The denitrification contribution to N2O production (R2 = 0.44, p < 0.01) and N2O reduction degree (R2 = 0.70, p < 0.01) were positively related to the dissolved organic carbon (DOC) content. Similar to urban rivers and eutrophic lakes, denitrification was the primary process responsible for N2O production (43.0%) in certain reaches with high organic content (DOC = 5.29 mg/L). Nevertheless, the denitrification activity was generally constrained by the availability of electron donors (average DOC = 2.51 mg/L) throughout the Yellow River basin. Consequently, nitrification emerged as the primary contributor in the well-oxygenated Yellow River. Additionally, our findings further distinguished the respective contribution of ammonia-oxidizing bacteria (AOB) and archaea (AOA) to N2O emissions. Although AOB dominated the N2O production in the Yellow River, the AOA specie abundance (AOA/(AOA + AOB)) contributed up to 32.6%, which resulted in 25.6% of the total nitrifier-produced N2O, suggesting a significant occurrence of AOA in the oligotrophic Yellow River. Overall, this study provided a non-invasive approach for quantifying the microbial sources and sinks to N2O emissions, and demonstrated the substantial role of nitrification in the large oligotrophic rivers.

[Effects of Personalized Exercise Prescriptions on Sarcopenia in Patients Undergoing Hemodialysis].

Sarcopenia is a major factor affecting the health and quality of life of the patients undergoing hemodialysis.Exercise can effectively ameliorate sarcopenia in these patients.However,the type,intensity,time,and frequency of exercise influence the effect of exercise.This review describes the effects of different exercise prescriptions on sarcopenia in the patients undergoing hemodialysis.It aims to assist medical staff in developing personalized exercise prescriptions,guiding patients to engage in exercise,and provide effective strategies for the prevention and treatment of sarcopenia in the patients undergoing hemodialysis.

Sedanolide alleviates DSS-induced colitis by modulating the intestinal FXR-SMPD3 pathway in mice.

INTRODUCTION: Inflammatory bowel disease (IBD) is a global disease with limited therapy. It is reported that sedanolide exerts anti-oxidative and anti-inflammatory effects as a natural phthalide, but its effects on IBD remain unclear. OBJECTIVES: In this study, we investigated the impacts of sedanolide on dextran sodium sulfate (DSS)-induced colitis in mice. METHODS: The mice were administered sedanolide or vehicle followed by DSS administration, after which colitis symptoms, inflammation levels, and intestinal barrier function were evaluated. Transcriptome analysis, 16S rRNA sequencing, and targeted metabolomics analysis of bile acids and lipids were performed. RESULTS: Sedanolide protected mice from DSS-induced colitis, suppressed the inflammation, restored the weakened epithelial barrier, and modified the gut microbiota by decreasing bile salt hydrolase (BSH)-expressing bacteria. The downregulation of BSH activity by sedanolide increased the ratio of conjugated/unconjugated bile acids (BAs), thereby inhibiting the intestinal farnesoid X receptor (FXR) pathway. The roles of the FXR pathway and gut microbiota were verified using an intestinal FXR-specific agonist (fexaramine) and germ-free mice, respectively. Furthermore, we identified the key effector ceramide, which is regulated by sphingomyelin phosphodiesterase 3 (SMPD3). The protective effects of ceramide (d18:1/16:0) against inflammation and the gut barrier were demonstrated in vitro using the human cell line Caco-2. CONCLUSION: Sedanolide could reshape the intestinal flora and influence BA composition, thus inhibiting the FXR-SMPD3 pathway to stimulate the synthesis of ceramide, which ultimately alleviated DSS-induced colitis in mice. Overall, our research revealed the protective effects of sedanolide against DSS-induced colitis in mice, which indicated that sedanolide may be a clinical treatment for colitis. Additionally, the key lipid ceramide (d18:1/16:0) was shown to mediate the protective effects of sedanolide, providing new insight into the associations between colitis and lipid metabolites.

The virtual staining method by quantitative phase imaging for label free lymphocytes based on self-supervised iteration cycle-consistent adversarial networks.

Quantitative phase imaging (QPI) provides 3D structural and morphological information for label free living cells. Unfortunately, this quantitative phase information cannot meet doctors' diagnostic requirements of the clinical "gold standard," which displays stained cells' pathological states based on 2D color features. To make QPI results satisfy the clinical "gold standard," the virtual staining method by QPI for label free lymphocytes based on self-supervised iteration Cycle-Consistent Adversarial Networks (CycleGANs) is proposed herein. The 3D phase information of QPI is, therefore, trained and transferred to a kind of 2D "virtual staining" image that is well in agreement with "gold standard" results. To solve the problem that unstained QPI and stained "gold standard" results cannot be obtained for the same label free living cell, the self-supervised iteration for the CycleGAN deep learning algorithm is designed to obtain a trained stained result as the ground truth for error evaluation. The structural similarity index of our virtual staining experimental results for 8756 lymphocytes is 0.86. Lymphocytes' area errors after converting to 2D virtual stained results from 3D phase information are less than 3.59%. The mean error of the nuclear to cytoplasmic ratio is 2.69%, and the color deviation from the "gold standard" is less than 6.67%.

Changes in Novel Biomarkers for Protein Oxidation in Pork Patties under Different Cooking Methods.

The aim of this study was to assess the effectiveness of different biomarkers to identify the levels of protein oxidation in pork patties induced by assorted cooking methods. To achieve this purpose, pork patties prepared from longissimus dorsi were cooked using three methods (frying, steaming, and roasting) at different internal temperatures (60, 70, 80, and 90 °C). Traditional biomarkers including total carbonyl and total thiol and novel biomarkers including α-aminoadipic semialdehyde (AAS) and lysinonorleucine (LNL) were determined. Results demonstrated that total thiol and AAS were the most successful biomarkers in distinguishing the three cooking methods in relation to protein oxidation, with AAS being the most sensitive. Moreover, as indicated by the biomarkers of total thiol and AAS, frying caused the highest level of protein oxidation, while steaming resulted in the lowest level when pork patties were cooked to the internal temperatures of 70 or 80 °C.

Opsonization Inveigles Macrophages Engulfing Carrier-Free Bilirubin/JPH203 Nanoparticles to Suppress Inflammation for Osteoarthritis Therapy.

Osteoarthritis (OA) is a chronic inflammatory disease characterized by cartilage destruction, synovitis, and osteophyte formation. Disease-modifying treatments for OA are currently lacking. Because inflammation mediated by an imbalance of M1/M2 macrophages in the synovial cavities contributes to OA progression, regulating the M1 to M2 polarization of macrophages can be a potential therapeutic strategy. Basing on the inherent immune mechanism and pathological environment of OA, an immunoglobulin G-conjugated bilirubin/JPH203 self-assembled nanoparticle (IgG/BRJ) is developed, and its therapeutic potential for OA is evaluated. After intra-articular administration, IgG conjugation facilitates the recognition and engulfment of nanoparticles by the M1 macrophages. The internalized nanoparticles disassemble in response to the increased oxidative stress, and the released bilirubin (BR) and JPH203 scavenge reactive oxygen species (ROS), inhibit the nuclear factor kappa-B pathway, and suppress the activated mammalian target of rapamycin pathway, result in the repolarization of macrophages and enhance M2/M1 ratios. Suppression of the inflammatory environment by IgG/BRJ promotes cartilage protection and repair in an OA rat model, thereby improving therapeutic outcomes. This strategy of opsonization involving M1 macrophages to engulf carrier-free BR/JPH203 nanoparticles to suppress inflammation for OA therapy holds great potential for OA intervention and treatment.

Automated detection of small bowel lesions based on capsule endoscopy using deep learning algorithm.

BACKGROUND: In order to overcome the challenges of lesion detection in capsule endoscopy (CE), we improved the YOLOv5-based deep learning algorithm and established the CE-YOLOv5 algorithm to identify small bowel lesions captured by CE. METHODS: A total of 124,678 typical abnormal images from 1,452 patients were enrolled to train the CE-YOLOv5 model. Then 298 patients with suspected small bowel lesions detected by CE were prospectively enrolled in the testing phase of the study. Small bowel images and videos from the above 298 patients were interpreted by the experts, non-experts and CE-YOLOv5, respectively. RESULTS: The sensitivity of CE-YOLOv5 in diagnosing vascular lesions, ulcerated/erosive lesions, protruding lesions, parasite, diverticulum, active bleeding and villous lesions based on CE videos was 91.9 %, 92.2 %, 91.4 %, 93.1 %, 93.3 %, 95.1 %, and 100 % respectively. Furthermore, CE-YOLOv5 achieved specificity and accuracy of more than 90 % for all lesions. Compared with experts, the CE-YOLOv5 showed comparable overall sensitivity, specificity and accuracy (all P > 0.05). Compared with non-experts, the CE-YOLOv5 showed significantly higher overall sensitivity (P < 0.0001) and overall accuracy (P < 0.0001), and a moderately higher overall specificity (P = 0.0351). Furthermore, the time for AI-reading (5.62 ± 2.81 min) was significantly shorter than that for the other two groups (both P < 0.0001). CONCLUSIONS: CE-YOLOv5 diagnosed small bowel lesions in CE videos with high sensitivity, specificity and accuracy, providing a reliable approach for automated lesion detection in real-world clinical practice.

Developing and validating a clinlabomics-based machine-learning model for early detection of retinal detachment in patients with high myopia.

BACKGROUND: Retinal detachment (RD) is a vision-threatening disorder of significant severity. Individuals with high myopia (HM) face a 2 to 6 times higher risk of developing RD compared to non-myopes. The timely identification of high myopia-related retinal detachment (HMRD) is crucial for effective treatment and prevention of additional vision impairment. Consequently, our objective was to streamline and validate a machine-learning model based on clinical laboratory omics (clinlabomics) for the early detection of RD in HM patients. METHODS: We extracted clinlabomics data from the electronic health records for 24,440 HM and 5607 HMRD between 2015 and 2022. Lasso regression analysis assessed fifty-nine variables, excluding collinear variables (variance inflation factor > 10). Four models based on random forest, gradient boosting machine (GBM), generalized linear model, and Deep Learning Model were trained for HMRD diagnosis and employed for internal validation. An external test of the models was done. Three random data sets were further processed to validate the performance of the diagnostic model. The primary outcomes were the area under the receiver operating characteristic curve (AUC) and the area under the precision-recall curve (AUCPR) to diagnose HMRD. RESULTS: Nine variables were selected by all models. Given the AUC and AUCPR values across the different sets, the GBM model was chosen as the final diagnostic model. The GBM model had an AUC of 0.8550 (95%CI = 0.8322-0.8967) and an AUCPR of 0.5584 (95%CI = 0.5250-0.5879) in the training set. The AUC and AUCPR in the internal validation were 0.8405 (95%CI = 0.8060-0.8966) and 0.5355 (95%CI = 0.4988-0.5732). During the external test evaluation, it reached an AUC of 0.7579 (95%CI = 0.7340-0.7840) and an AUCPR of 0.5587 (95%CI = 0.5345-0.5880). A similar discriminative capacity was observed in the three random data sets. The GBM model was well-calibrated across all the sets. The GBM-RD model was implemented into a web application that provides risk prediction for HM individuals. CONCLUSION: GBM algorithms based on nine features successfully predicted the diagnosis of RD in patients with HM, which will help ophthalmologists to establish a preliminary diagnosis and to improve diagnostic accuracy in the clinic.

Development and characterization of 40 InDel markers from the major histocompatibility complex genes of largemouth bass (Micropterus salmoides).

BACKGROUND: The genetic improvement in growth and food habit domestication of largemouth bass (Micropterus salmoides) have made breakthroughs in past decades, while the relevant work on disease resistance were rarely carried out. Major histocompatibility complex (MHC) genes, which are well known as their numbers and high polymorphisms, have been used as candidate genes to mine disease-resistant-related molecular markers in many species. METHODS AND RESULTS: In present study, we developed and characterized 40 polymorphic and biallelic InDel markers from the major histocompatibility complex genes of largemouth bass. The minor allele frequency, observed heterozygosity, expected heterozygosity and polymorphic information content of these markers ranged from 0.0556 to 0.5000, 0.1111 to 0.6389, 0.1064 to 0.5070, and 0.0994 to 0.3750, respectively. Three loci deviated significantly from Hardy-Weinberg equilibrium, while linkage disequilibrium existed at none of these loci. CONCLUSION: These InDel markers might provide references for the further correlation analysis and molecular assisted selection of disease resistance in largemouth bass.

High diversity, abundance, and expression of hydrogenases in groundwater.

Hydrogen may be the most important electron donor available in the subsurface. Here we analyse the diversity, abundance and expression of hydrogenases in 5 proteomes, 25 metagenomes, and 265 amplicon datasets of groundwaters with diverse geochemistry. A total of 1545 new [NiFe]-hydrogenase gene sequences were recovered, which considerably increased the number of sequences (1999) in a widely used database. [NiFe]-hydrogenases were highly abundant, as abundant as the DNA-directed RNA polymerase. The abundance of hydrogenase genes increased with depth from 0 to 129 m. Hydrogenases were present in 481 out of 1245 metagenome-assembled genomes. The relative abundance of microbes with hydrogenases accounted for ~50% of the entire community. Hydrogenases were actively expressed, making up as much as 5.9% of methanogen proteomes. Most of the newly discovered diversity of hydrogenases was in "Group 3b", which has been associated with sulfur metabolism. "Group 3d", facilitating the interconversion of electrons between hydrogen and NAD, was the most abundant and mainly observed in methanotrophs and chemoautotrophs. "Group 3a", associated with methanogenesis, was the most abundant in proteomes. Two newly discovered groups of [NiFe]-hydrogenases, observed in Methanobacteriaceae and Anaerolineaceae, further expanded diversity. Our results highlight the vast diversity, abundance and expression of hydrogenases in groundwaters, suggesting a high potential for hydrogen oxidation in subsurface habitats.

Protective effect of Pediococcus pentosaceus Li05 on diarrhea-predominant irritable bowel syndrome in rats.

Pediococcus pentosaceus Li05 (Li05) has demonstrated potential benefits in various intestinal and liver diseases, but its potential and mechanisms in relieving diarrhea have not been understood. The objective of this research was to examine the effects and mechanisms of Li05 in rats with diarrhea-predominant irritable bowel syndrome (IBS-D) induced by wrap restrain stress (WRS) and 4% acetic acid. The results demonstrated that Li05 effectively alleviated weight loss, visceral sensitivity and diarrhea in rats with IBS-D. It also improved intestinal and systemic inflammation by reducing the levels of chemokines and proinflammatory cytokines (GRO/KC, RANTES, IL-1ß, IL-7, and IL-18). The 5-hydroxytryptamine (5-HT) signaling pathway is involved in regulating excessive intestinal motility and secretion in IBS-D. Li05 effectively reduced the expression levels of the 5-HT3B receptor (5-HT3BR) (p < 0.01) in the intestine. Additionally, Li05 intervention had a regulatory effect on the gut composition, with a decrease in the abundance of [Ruminococcus] gauvreauii group, Dubosiella, Erysipelatoclostridium and Blautia, and an increase in the abundance of Alloprevotella, Anaerotruncus and Mucispirillum. Furthermore, Li05 induced significant changes in fatty acid and amino acid metabolism in the gut of rats with IBS-D. These findings indicate that Li05 exhibits an effective improvement in IBS-D symptoms by reducing inflammation and modulating gut microbiota and metabolism. Based on the above results, Li05 holds promise as a potential probiotic for managing IBS-D.

Metabolomics identifies and validates serum androstenedione as novel biomarker for diagnosing primary angle closure glaucoma and predicting the visual field progression.

Background: Primary angle closure glaucoma (PACG) is the leading cause of irreversible blindness in Asia, and no reliable, effective diagnostic, and predictive biomarkers are used in clinical routines. A growing body of evidence shows metabolic alterations in patients with glaucoma. We aimed to develop and validate potential metabolite biomarkers to diagnose and predict the visual field progression of PACG. Methods: Here, we used a five-phase (discovery phase, validation phase 1, validation phase 2, supplementary phase, and cohort phase) multicenter (EENT hospital, Shanghai Xuhui Central Hospital), cross-sectional, prospective cohort study designed to perform widely targeted metabolomics and chemiluminescence immunoassay to determine candidate biomarkers. Five machine learning (random forest, support vector machine, lasso, K-nearest neighbor, and GaussianNaive Bayes [NB]) approaches were used to identify an optimal algorithm. The discrimination ability was evaluated using the area under the receiver operating characteristic curve (AUC). Calibration was assessed by Hosmer-Lemeshow tests and calibration plots. Results: Studied serum samples were collected from 616 participants, and 1464 metabolites were identified. Machine learning algorithm determines that androstenedione exhibited excellent discrimination and acceptable calibration in discriminating PACG across the discovery phase (discovery set 1, AUCs=1.0 [95% CI, 1.00-1.00]; discovery set 2, AUCs = 0.85 [95% CI, 0.80-0.90]) and validation phases (internal validation, AUCs = 0.86 [95% CI, 0.81-0.91]; external validation, AUCs = 0.87 [95% CI, 0.80-0.95]). Androstenedione also exhibited a higher AUC (0.92-0.98) to discriminate the severity of PACG. In the supplemental phase, serum androstenedione levels were consistent with those in aqueous humor (r=0.82, p=0.038) and significantly (p=0.021) decreased after treatment. Further, cohort phase demonstrates that higher baseline androstenedione levels (hazard ratio = 2.71 [95% CI: 1.199-6.104], p=0.017) were associated with faster visual field progression. Conclusions: Our study identifies serum androstenedione as a potential biomarker for diagnosing PACG and indicating visual field progression. Funding: This work was supported by Youth Medical Talents - Clinical Laboratory Practitioner Program (2022-65), the National Natural Science Foundation of China (82302582), Shanghai Municipal Health Commission Project (20224Y0317), and Higher Education Industry-Academic-Research Innovation Fund of China (2023JQ006).

Short-, long-read metagenome and virome reveal the profile of phage-mediated ARGs in anoxic-oxic processes for swine wastewater treatment.

Phages are among the most widely spread viruses, but their profiles and the antibiotic resistance genes (ARGs) they carry in swine wastewater remain underexplored. The present study investigated the distribution characteristics of phages and their ARG risk in anoxic/oxic (A/O) wastewater treatment processes of swine farms using short- and long-read metagenome and virome. The results demonstrated that the virome could extract more phage sequences than the total metagenome; thus, it was more suited for studying phages in wastewater settings. Intriguingly, phages had significantly lower abundance of ARG than ARGs harbored by total microorganisms (P < 0.01). Eleven ARGs co-occurred with phages and bacteria (R > 0.6 and P < 0.05), with Siphoviridae being the phage co-occurring with the most ARGs (5). Horizontal gene transfer (HGT) events were observed between Proteobacteria and the major phyla except for Bacteroidota. Furthermore, there were prophage sequences and ARGs on the same contig in bacterial MAGs. These data strongly demonstrate that phages promote horizontal transfer of ARG between bacterial hosts in A/O processes for swine wastewater treatment. Therefore, the risk of phage-mediated horizontal transfer of ARGs cannot be overlooked despite the low abundance of phage ARGs (pARG).

Tailoring Interfaces of All-Carbon Electromagnetic Interference Shielding Materials for Boosting Comprehensive Performance.

Electromagnetic interference (EMI) shielding materials with lightweight, high shielding effectiveness, excellent chemical stability, especially minimized secondary electromagnetic pollution, are urgently desired for integrated electronic systems operating in harsh working environments. Here in this study, by systematically engineering and matching the interfacial properties of carbon-based membrane materials, i.e., graphite paper, whisker carbon nanotube paper (WCNT paper), carbon nanotube film (CNT film), bucky paper (BP), and carbon cloth (CC) with three-dimensional (3D) porous carbon nanotube sponge (CNTS), we successfully constructed a series of multifunctional all-carbon EMI shielding materials, which exhibit excellent average shielding effectiveness of over 90 dB with a thickness of about 1 mm and dramatically minimized secondary electromagnetic reflection. Moreover, benefiting from the all-carbon nature and engineered interfaces, our CMC materials also exhibit excellent photothermal and Joule heating performances. These results not only provide guidance for designing advanced multifunctional all-carbon EMI shielding materials but also shed light on the hidden mechanism between interfaces and performances of composite materials.

Expression characteristics of the cyp19a1b aromatase gene and its response to 17ß-estradiol treatment in largemouth bass (Micropterus salmoides).

To investigate the regulatory role of the cyp19a1b aromatase gene in the sexual differentiation of largemouth bass (Micropterus salmoides, LMB), we obtained the full-length cDNA sequence of cyp19a1b using rapid amplification of cDNA ends technique. Tissue expression characteristics and feedback with 17-ß-estradiol (E2) were determined using quantitative real-time PCR (qRT-PCR), while gonad development was assessed through histological section observations. The cDNA sequence of LMB cyp19a1b was found to be1950 base pairs (bp) in length, including a 5' untranslated region of 145 bp, a 3' untranslated region of 278 bp, and an open reading frame encoding a protein consisting of 1527 bp that encoded 508 amino acids. The qRT-PCR results indicated that cyp19a1b abundantly expressed in the brain, followed by the gonads, and its expression in the ovaries was significantly higher than that observed in the testes (P < 0.05). After feeding fish with E2 for 30 days, the expression of cyp19a1b in the pseudo-female gonads (XY-F) was significantly higher than that in males (XY-M) (P < 0.05), whereas expression did not differ significantly between XX-F and XY-F fish (P > 0.05). Although the expression of cyp19a1b in XY-F and XX-F fish was not significantly different after 60 days (P>0.05), both exhibited significantly higher levels than that of XY-M fish (P<0.05). Histological sections analysis showed the presence of oogonia in both XY-F and XX-F fish at 30 days, while spermatogonia were observed in XY-M fish. At 60 days, primary oocytes were abundantly observed in both XY-F and XX-F fish, while a few spermatogonia were visible in XY-M fish. At 90 days, the histological sections' results showed that a large number of oocytes were visible in XY-F and XX-F fish. Additionally, the gonads of XY-M fish contained numerous spermatocytes. These results suggest that cyp19a1b plays a pivotal role in the development of ovaries and nervous system development in LMB.

Graphene oxide stimulated low-temperature denitrification activity of microbial communities in lake sediments by enhancing anabolism and inhibiting cellular respiration.

Nitrate pollution in fresh water is becoming increasingly serious. In this study, the effects of temperature and graphene oxide materials on the potential functions of denitrification communities in lake sediments were investigated by metagenome. The addition of graphene oxide significantly affected the abundance of denitrification genes such as Nap, Nos, and enhanced the contribution of Pseudomonas, making low temperature and material addition conducive to the denitrification process. Module network implied that low temperature increased the centrality of denitrification in community functions. At low temperatures, graphene oxide enhanced community anabolism by stimulation organic carbon consumption and regulating the gene abundance in the citric acid cycle and the semi-phosphorylation Entner-Doudoroff, thus possibly stimulating extracellular polymeric substances (EPS) synthesis and secretion. In addition, graphene oxide may also regulate the transfer of reducing electrons from NADH to denitrifying enzymes by affecting the gene abundances of complex I and complex IV.

Relish-facilitated lncRNA-CR11538 suppresses Drosophila Imd immune response and maintains immune homeostasis via decoying Relish away from antimicrobial peptide promoters.

Innate immunity plays a crucial role in host defense against pathogen invasion and its strength and duration requires precise control. Long non-coding RNAs (lncRNAs) have become important regulators of innate immunity, yet their roles in Drosophila immune responses remain largely unknown. In this study, we identified that the overexpression of lncRNA-CR11538 inhibits the expression of antimicrobial peptides (AMPs) Dpt and AttA in Drosophila upon Escherichia coli (E. coli) infection, and influences the survival rate of flies after E. cloacae infection. Mechanically, lncRNA-CR11538 decoys Relish away from AMPs promoter region. We further revealed that Relish can promote the transcription of lncRNA-CR11538. After analyzing the dynamic expression profile of lncRNA-CR11538 during Imd immune response, we put forward a hypothesis that in the late stage of Imd immune response, lncRNA-CR11538 can be activated by Relish and further decoy Relish away from the AMPs promoter to suppress excessive immune signal and maintain immune homeostasis. This mechanism we proposed provides insights into the complex regulatory networks controlling immune responses in Drosophila and suggests potential targets for therapeutic intervention in diseases involving dysregulated immune responses.

Association Between Advanced Glycation End Products and Sarcopenia: The Mediating Role of Osteoporosis.

CONTEXT: Advanced glycation end products (AGEs) are a group of molecules formed through nonenzymatic reactions. These compounds are associated with several age-related diseases, including sarcopenia and osteoporosis. OBJECTIVE: This work aimed to investigate the relationships between AGEs, osteoporosis, and sarcopenia in community-dwelling older adults. METHODS: This cross-sectional study included 1991 older adults aged 72.37 ± 5.90 years from China. AGE levels were measured by the AGE Reader device. Bone mineral density was assessed using dual-energy X-ray absorptiometry, and osteoporosis was diagnosed based on a T score of less than -2.5. Sarcopenia was defined as loss of muscle mass plus loss of muscle strength and/or reduced physical performance. Presarcopenia was defined as low muscle mass with normal muscle strength and normal physical performance. RESULTS: The prevalence of sarcopenia was 18.5%, and that of osteoporosis was 40.5%. Compared to the lowest AGE quartile, the highest AGE quartile showed a significant association with sarcopenia (odds ratio [OR] 2.42; 95% CI, 1.60-3.66) (P for trend <.001), but not with presarcopenia. Per-SD increase in AGE was associated with higher odds of sarcopenia (OR 1.44; 95% CI, 1.26-1.66). Additionally, in the mediation analysis, when AGEs were treated as a continuous variable (the mediation effect is denoted by Za*Zb = 18.81; 95% CI, 8.07-32.32]-the 95% CI does not contain zero, representing a significant mediating effect) or a categorical variable (the mediating effect is expressed as Zmediation = 3.01 > 1.96, which represents a significant mediating effect), osteoporosis played a partial mediating role in the association between AGEs and sarcopenia. CONCLUSION: Elevated AGEs are associated with sarcopenia but not with presarcopenia. This association was partially mediated by osteoporosis.

Effects of partial reduction of polystyrene micro-nanoplastics on the immunity, gut microbiota and metabolome of mice.

Microplastic (MP) and nanoplastic (NP) could cause gut microbiota alterations. Although micro/nanoplastic (MNP) degradation is attracting increasing scientific interest, the evaluation of MNP reduction in gut needs to be further investigated. This study aimed to determine whether partial reduction of polystyrene MNP in gut could affect the immunity, gut microbiota and metabolome of mice. Serum eotaxin/CCL11 was at a lower level in the mice exposed to 200 µg and 500 µg NP (i.e., 2NP and 5NP groups, respectively) compared to those exposed to 500 µg MP (i.e., 5 MP group), while serum IL-2 and IL-4 were both greater in the 5NP group compared to the 5 MP group. The gut bacterial alpha diversity, fungal diversity and evenness were all similar among the MNP and control groups. However, the gut fungal richness was greater in both the 5NP and 5 MP groups compared to the control group. The gut bacterial and fungal compositions were both different between the MNP and control groups. Multiple gut bacteria and fungi showed different levels between the 2NP and 5NP groups, as well as between the 2NP and 5 MP groups. Increased Staphylococcus and decreased Glomus were determined in the 2NP group compared to both the 5NP and 5 MP groups. A Lactobacillus phylotype was found as the sole gatekeeper in the bacterial network of the 2NP group, while a Bifidobacterium phylotype contributed most to the stability of the bacterial networks of both the 5NP and 5 MP groups. Multiple differential gut metabolic pathways were found between the 2NP and 5NP/5 MP groups, and mTOR signaling pathway was largely upregulated in the 2NP group compared to both the 5NP and 5 MP groups. The relevant results could help with the evaluation of partial reduction of MNP in gut.