Exploring seasonal variations, assembly dynamics, and relationships of bacterial communities in different habitats of marine ranching.

Offshore coastal marine ranching ecosystems provide habitat for diverse and active bacterial communities. In this study, 16S rRNA gene sequencing and multiple bioinformatics methods were applied to investigate assembly dynamics and relationships in different habitats. The higher number of edges in the water network, more balanced ratio of positive and negative links, and more keystone species included in the co-occurrence network of water. Stochastic processes dominated in shaping gut and sediment community assembly (R2 < 0.5), while water bacterial community assembly were dominated by deterministic processes (R2 > 0.5). Dissimilarity-overlap curve model indicated that the communities in different habitats have general dynamics and interspecific interaction (P < 0.001). Bacterial source-tracking analysis revealed that the gut was more similar to the sediment than the water bacterial communities. In summary, this study provides basic data for the ecological study of marine ranching through the study of bacterial community dynamics.

The Role of LC3-Associated Phagocytosis Inhibits the Inflammatory Response in Aspergillus fumigatus Keratitis.

Purpose: The purpose of this study was to investigate the role and mechanism of microtubule-associated protein light chain-3 (LC3)-associated phagocytosis (LAP) in the immune response to Aspergillus fumigatus (A. fumigatus) keratitis. Methods: The formation of single-membrane phagosomes was visualized in the corneas of healthy or A. fumigatus-infected humans and C57BL/6 mice using transmission electron microscopy (TEM). Rubicon siRNA (si-Rubicon) was used to block Rubicon expression. RAW 264.7 cells or mice corneas were infected with A. fumigatus with or without pretreatment of si-Rubicon and scrambled siRNA. RAW 264.7 cells were pretreated with Dectin-1 antibody or Dectin-1 overexpressed plasmid and then stimulated with A. fumigatus. Flow cytometry was used to label macrophages in normal and infected corneas of mice. In mice with A. fumigatus keratitis, the severity of the disease was assessed using clinical scores. We used lentiviral technology to transfer GV348-Ubi-GFP-LC3-II-SV40-Puro Lentivirus into the mouse cornea. The GFP-LC3 fusion protein was visualized in corneal slices using a fluorescence microscope. We detected the mRNA and protein expressions of the inflammatory factors IL-6, IL-1ß, and IL-10 using real-time PCR (RT-PCR) and ELISA. We detected the expression of LAP-related proteins Rubicon, ATG-7, Beclin-1, and LC3-II using Western blot or immunofluorescence. Results: Accumulation of single-membrane phagosomes within macrophages was observed in the corneas of patients and mice with A. fumigatus keratitis using TEM. Flow cytometry (FCM) analysis results show that the number of macrophages in the cornea of mice significantly increases after infection with A. fumigatus. LAP-related proteins were significantly elevated in the corneas of mice and RAW 264.7 cells after infection with A. fumigatus. The si-Rubicon treatment elevated the clinical score of mice. In A. fumigatus keratitis mice, the si-Rubicon treated group showed significantly higher expression of IL-6 and IL-1ß and lower expression of IL-10 and LC3-II compared to the control group. In RAW 264.7 cells, treatment with the Dectin-1 overexpressed plasmid upregulated the expression of LAP-related proteins, a process that was significantly inhibited by the Dectin-1 antibody. Conclusions: LAP participates in the anti-inflammatory immune process of fungal keratitis (FK) and exerts an anti-inflammatory effect. LAP is regulated through the Dectin-1 signaling pathway in A. fumigatus keratitis.

Emergence of mcr-4.3 genes in a novel Shewanella specie isolated from the Arctic environment.

Mobile colistin resistance (mcr) genes are pivotal contributors to last-line of antimicrobial resistance in human infections. Shewanella, historically recognized as a natural environmental bacterium with metal reduction capabilities, recently has been observed in clinical settings. However, limited knowledge has been explored on genetic differences between strains from non-clinical and clinical strains. In this study, we conducted the whole genome sequencing on six Arctic strains, illustrated the phylogenetic relationships on published 393 Shewanella strains that categorized the genus into four lineages (L1 to L4). Over 86.4% of clinical strain group (CG) strains belonged to L1 and L4, carrying mcr-4 genes and a complete metal-reduction pathways gene cluster. Remarkably, a novel Arctic Shewanella strain in L3, exhibits similar genetic characteristics with CG strains that carried both mcr-4 genes and a complete metal reduction pathway gene cluster. It raised concerns about the transmission ability from environment to clinic setting causing in the potential infections, and emphasized the need for monitoring the emerging strains with human infections.

Calebin A attenuated inflammation in RAW264.7 macrophages and adipose tissue to improve hepatic glucose metabolism and hyperglycemia in high-fat diet-fed obese mice.

The increased incidence of obesity, which become a global health problem, requires more functional food products with minor side and excellent effects. Calebin A (CbA) is a non-curcuminoid compound, which is reported to be an effective treatment for lipid metabolism and thermogenesis. However, its ability and mechanism of action in improving obesity-associated hyperglycemia remain unclear. This study was designed to explore the effect and mechanism of CbA in hyperglycemia via improvement of inflammation and glucose metabolism in the adipose tissue and liver in high-fat diet (HFD)-fed mice. After 10 weeks fed HFD, obese mice supplemented with CbA (25 and 100 mg/kg) for another 10 weeks showed a remarkable reducing adiposity and blood glucose. CbA modulated M1/M2 macrophage polarization, ameliorated inflammatory cytokines, and restored adiponectin as well as Glut 4 expression in the adipose tissue. In the in vitro study, CbA attenuated pro-inflammatory markers while upregulated anti-inflammatory IL-10 in LPS + IFNγ-generated M1 phenotype macrophages. In the liver, CbA attenuated steatosis, inflammatory infiltration, and protein levels of inflammatory TNF-α and IL-6. Moreover, CbA markedly upregulated Adiponectin receptor 1, AMPK, and insulin downstream Akt signaling to improve glycogen content and increase Glut2 protein. These findings indicated that CbA may be a novel therapeutic approach to treat obesity and hyperglycemia phenotype targeting on adipose inflammation and hepatic insulin signaling.

Exploring Sources, Biological Functions, and Potential Applications of the Ubiquitous Marine Cyclic Dipeptide: A Concise Review of Cyclic Glycine-Proline.

Cyclic glycine-proline (cGP), a prevalent marine cyclic dipeptide, possesses a distinct pyrrolidine-2,5-dione scaffold, which contributes to the chemical diversity and broad bioactivities of cGP. The diverse sources from marine-related, endogenous biological, and synthetic pathways and the in vitro and in vivo activities of cGP are reviewed. The potential applications for cGP are also explored. In particular, the pivotal roles of cGP in regulating insulin-like growth factor-1 homeostasis, enhancing neuroprotective effects, and improving neurotrophic function in central nervous system diseases are described. The potential roles of this endogenous cyclic peptide in drug development and healthcare initiatives are also highlighted. This review underscores the significance of cGP as a fundamental building block in drug discovery with exceptional drug-like properties and safety. By elucidating the considerable value of cGP, this review aims to reignite interest in cGP-related research within marine medicinal chemistry and synthetic biology.

Association between anti-SSA autoantibodies and conduction disturbances in heart failure.

BACKGROUND: Conduction disturbances play an important role in the occurrence and development of heart failure (HF). Studies suggest autoantibodies may attack the conduction system. However, whether autoantibodies are associated with conduction disturbances in patients with HF is unclear. OBJECTIVE: The purpose of this study was to assess whether anti-SSA, anti-Ro/Sjögren syndrome-related antigen A antibodies known for congenital atrioventricular block (AVB), is associated with conduction disturbances in patients with HF. METHODS: This retrospective observational study used data from patients with HF who were admitted to Beijing Anzhen Hospital between January 2018 and June 2022. Patients who were tested for anti-SSA and had undergone electrocardiographic examination during hospitalization were included. Conduction disturbances, including AVB, bundle branch block (BBB), and intraventricular conduction delay, were confirmed by a cardiologist blinded to anti-SSA status. Univariate and multivariable logistic regression analyses were performed to assess the association between anti-SSA and conduction disturbances. RESULTS: A total of 766 patients were included in this study, of whom 70 (9.1%) were anti-SSA positive. Subjects who were anti-SSA positive showed a higher prevalence of AVB (20% vs 10.6%) and BBB (27.3 % vs 10.9 %), including both left BBB and right BBB (all P <.05). After adjusting for known risk factors, anti-SSA was independently associated with AVB (odds ratio [OR] 2.42; 95% confidence interval [CI] 1.18-5.43; P = .03) and BBB (OR 3.15; 95% CI 1.68-5.89; P <.001). CONCLUSION: Anti-SSA is independently associated with AVB and BBB in patients with HF. Further study of the role of autoantibodies in the development of conduction abnormalities in patients with HF to generate possible targeted treatments is required.

Comparison of Clinical Characteristics and Treatment Outcome Between Localized and Disseminated Nocardiosis in a Tertiary Hospital in China.

Background: In China, due to the large population, infections caused by Nocardia may not be as rare. Unfortunately, there is still inadequate knowledge of the clinical impact caused by Nocardia. This study aimed to compare the clinical characteristics and treatment of localized and disseminated nocardiosis. Methods: The clinical and microbiological data of patients diagnosed with nocardiosis in a tertiary hospital in Beijing from July 2011 to July 2021 were collected and retrospectively analyzed. Results: Among the 54 nocardiosis cases, 34 cases were in the localized infection group, while 20 cases in the disseminated infection group. The proportion of patients with chronic structural lung disease was higher in the localized group (P=0.010). In contrast, patients with disseminated infections were more prone to receive long-term glucocorticoids and/or immunosuppressants (P=0.027). Pulmonary nodules were prominent features of imaging changes in patients with disseminated infections (P=0.027) whereas bronchial dilatation was more common in patients with localized infections (P=0.025). In addition, the disseminated group had longer average hospitalization days relative to the localized group (P=0.016), but there was no significant difference in mortality between them (P=0.942). Conclusion: There were differences in the clinical profiles between patients with localized and disseminated nocardiosis in terms of clinical presentation, infection site, radiological features, treatment, and prognosis. These findings may provide references for the management and treatment of patients with nocardiosis.

The effect of stretching exercises before orthotic treatment on the immediate in-orthosis correction of the patients with adolescent idiopathic scoliosis: A pilot study.

BACKGROUND: Stretching exercise is generally used for improving flexibility. However, its application to promote orthotic treatment for patients with adolescent idiopathic scoliosis (AIS) remains unknown. OBJECTIVE: This study was to explore the effect of pre-orthosis stretching exercises on spinal flexibility and initial in-orthosis correction for the patients with AIS. STUDY DESIGN: A pilot-controlled study. METHODS: An experimental group (EG) of 13 subjects (10 girls and 3 boys) with AIS allocating to self-stretching exercises and a control group (CG) of 19 AIS subjects (14 girls and 5 boys) with no stretching before orthosis fitting were recruited. The spinal flexibility of the EG was evaluated with an ultrasound imaging system and physical measurements. The initial in-orthosis correction rates between the 2 groups were compared with the independent t test, and the correlation analysis between the spinal flexibility measured from ultrasound images and physical measurement was performed with the Pearson correlation test. RESULTS: The initial Cobb angle of EG and CG were 25.70° ± 7.30° and 28.09° ± 5.58°, respectively. No significant difference was observed between the initial in-orthosis Cobb angle of EG (11.13° ± 6.80°) and CG (15.65° ± 9.10°) (p = 0.06). However, the spinal flexibility after stretching exercises was improved (p < 0.001), and the spinal flexibility changes measured with ultrasound and physical forward-bending method were significantly correlated (r = 0.57, p < 0.05). CONCLUSION: Stretching exercises before orthotic treatment could improve the spinal flexibility but did not cause a better in-orthosis correction. A study with a larger sample size and longer follow-up period should be conducted to investigate the long-term effect of stretching exercises.

Temporal regulation of MDA5 inactivation by Caspase-3 dependent cleavage of 14-3-3η.

The kinetics of type I interferon (IFN) induction versus the virus replication compete, and the result of the competition determines the outcome of the infection. Chaperone proteins that involved in promoting the activation kinetics of PRRs rapidly trigger antiviral innate immunity. We have previously shown that prior to the interaction with MAVS to induce type I IFN, 14-3-3η facilitates the oligomerization and intracellular redistribution of activated MDA5. Here we report that the cleavage of 14-3-3η upon MDA5 activation, and we identified Caspase-3 activated by MDA5-dependent signaling was essential to produce sub-14-3-3η lacking the C-terminal helix (αI) and tail. The cleaved form of 14-3-3η (sub-14-3-3η) could strongly interact with MDA5 but could not support MDA5-dependent type I IFN induction, indicating the opposite functions between the full-length 14-3-3η and sub-14-3-3η. During human coronavirus or enterovirus infections, the accumulation of sub-14-3-3η was observed along with the activation of Caspase-3, suggesting that RNA viruses may antagonize 14-3-3η by promoting the formation of sub-14-3-3η to impair antiviral innate immunity. In conclusion, sub-14-3-3η, which could not promote MDA5 activation, may serve as a negative feedback to return to homeostasis to prevent excessive type I IFN production and unnecessary inflammation.

Boron nitride microfiber reinforced polyacrylic acid hydrogels with excellent self-adhesion, fast pH response, and strain sensitivity.

Hydrogels are widely utilized in the sensor field, but their inadequate adhesion presents a significant obstacle. Herein, a new multifunctional BNMFs/PAA composite hydrogel was prepared via the incorporation of one-dimensional porous boron nitride microfibers (BNMFs) and polyacrylic acid (PAA) hydrogels. BNMFs, as a reinforcing filler, play a very important role in enhancing the properties of the composite hydrogels. In particular, the porous micrometer structure plays a unique role in improving the adhesion properties of PAA hydrogels. The steric hindrance and the rich hydroxyl functional groups coming from BNMFs are key factors for the excellent adhesion of the composite hydrogels. The composite hydrogels show strong adhesion to various substrate materials. For iron plates and biological tissues, the adhesion energy can reach 1377 J m-2 and 317 J m-2, respectively. In addition, the developed BNMFs/PAA composite hydrogels exhibit excellent mechanical properties. The fracture strain of the composite hydrogels is increased by 2.4 times compared to pure PAA hydrogels. The hydrogen bonds formed between BNMFs and PAA are conducive to the mechanical properties of the BNMFs/PAA composite hydrogels. Meanwhile, BNMFs as fillers play a role in carrying and dissipating force. Furthermore, the BNMFs/PAA composite hydrogels have excellent strain and pH response characteristics. This is because the crosslinking network of the composite hydrogels becomes loose after the addition of BNMFs, resulting in rapid ion transport pathways. Therefore, the developed BNMFs/PAA composite hydrogels will have broad application prospects in the fields of motion monitoring, intelligent skin and biological adhesives.

Dissecting Exciton Dynamics in pH-Activatable Long-Wavelength Photosensitizers for Traceable Photodynamic Therapy.

Tumor-specific activatable long-wavelength (LW) photosensitizers (PSs) show promise in overcoming the limitations of traditional photodynamic therapy (PDT), such as systemic phototoxicity and shallow tissue penetration. However, their insufficient LW light absorption and low singlet oxygen quantum yield (F1O2) usually require high laser power density to produce thermal energy and synergistically enhance PDT. The strong photothermal radiation causing acute pain significantly reduces patient compliance and hinders the broader clinical application of LW PDT. Through the exciton dynamics dissection strategy, we have developed a series of pH-activatable cyanine-based LW PSs (LET-R, R = H, Cl, Br, I), among which the activated LET-I exhibits strong light absorption at 808 nm and a remarkable 3.2-fold enhancement in F1O2 compared to indocyanine green. Transient spectroscopic analysis and theoretical calculations confirmed its significantly promoted intersystem crossing and simultaneously enhanced LW fluorescence emission characteristics. These features enable the activatable fluorescence and photoacoustic dual-modal imaging-escorted complete photodynamic eradication of tumors by the folic acid (FA)-modified LET-I probe (LET-I-FA), under the ultralow 808 nm laser power density (0.2 W cm-2) for irradiation, without the need for photothermal energy synergy. This research presents a novel strategy of dissecting exciton dynamics to screen activatable LW PSs for traceable PDT.

Protecting primary teeth from dental erosion through bioactive glass.

OBJECTIVES: The present study aimed to evaluate the effectiveness of bioactive glass (BAG) in preventing dental erosion in primary teeth. METHODS: Enamel and dentin specimens (2 × 2 × 2 mm) were obtained from extracted primary teeth, which were randomly divided into the following groups based on the pretreatments (n = 12): DW (deionized water), NaF (2 % sodium fluoride), 2BAG (2 % BAG), 4BAG (4 % BAG), 6BAG (6 % BAG), and 8BAG (8 % BAG). The specimens were immersed in the respective solutions for 2 min and subjected to in vitro erosive challenges (4 × 5 min/d) for 5 d. The erosive enamel loss (EEL), erosive dentin loss (EDL), and the thickness of the demineralized organic matrix (DOM) were measured using a contact profilometer. The surface microhardness (SMH) was measured, and the percentage of SMH loss (%SMHL) was calculated. The surface morphology and mineral composition were evaluated by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS), respectively. RESULTS: After the erosive challenges, the EEL, EDL, and%SMHL of the 2BAG, 4BAG, 6BAG, and 8BAG groups significantly reduced, with the greatest reduction was observed in the 6BAG (EEL: 6.5 ± 0.2 µm;%SMHL in enamel: 12.8 ± 2.6; EDL: 7.9 ± 0.3 µm; %SMHL in dentin: 22.1 ± 2.7) and 8BAG groups (EEL: 6.4 ± 0.4 µm;%SMHL in enamel: 11.0 ± 1.9; EDL: 7.8 ± 0.5 µm; %SMHL in dentin: 22.0 ± 2.5) (P < 0.05). With increasing BAG concentrations, the number of surface deposits containing Ca, P, and Si increased. CONCLUSIONS: 6BAG was the most effective for preventing dental erosion in primary teeth and showed a particularly strong potential for dentin erosion prevention. CLINICAL SIGNIFICANCE: Bioactive glass, especially at a 6 % concentration, has proven effective in reducing erosive tooth wear and surface microhardness loss while also protecting demineralized organic matrix in primary dentin.

Comparison of "Huaxi-1" or "histidine-tryptophan-ketoglutarate" cardioplegia in an animal model.

Background: Using a pig model of cardiopulmonary bypass, we compared outcomes after cardioplegia either with our in-house "Huaxi-1" solution containing natural blood and crystalloid or with the entirely crystalloid, commercially available "histidine-tryptophan-ketoglutarate" solution. Methods: Cardiopulmonary bypass was established in 12 healthy male pigs, who were randomized to receive a single dose of either Huaxi-1 or entirely crystalloid. All animals were then subjected to whole-heart ischemia for 90 min, followed by 2 h of reperfusion, after which myocardial injury was assessed in terms of cardiac function, myocardial pathology and levels of biomarkers in plasma, while levels of high-energy phosphate in myocardium were assayed using liquid chromatography. Results: Animals given Huaxi-1 cardioplegia required significantly less time to be weaned off bypass, they received significantly lower doses of norepinephrine, and they showed significantly higher levels (mean ± SD) of adenosine triphosphate (14 ± 4 vs. 8 ± 2 µg/mg, P = 0.005), adenosine diphosphate (16 ± 2 vs. 13 ± 2 µg/mg, P = 0.046), and total adenine nucleotide (37 ± 4 vs. 30 ± 3 µg/mg, P = 0.006) in myocardium after 2 h of reperfusion. They also showed less severe bleeding, edema and injury to mitochondria and myofibers in myocardium. The two groups did not differ significantly in doses of inotropic drugs received, cardiac output or levels of biomarkers in plasma. Conclusions: In this animal model of healthy hearts subjected to 90 min of ischemia, Huaxi-1 cardioplegia may be superior to entirely crystalloid cardioplegia for promoting energy generation and attenuating ischemia/reperfusion injury in myocardium.

Turbidity-tolerant underwater wireless optical communications using dense blue-green wavelength division multiplexing.

Underwater wireless optical communication (UWOC) has demonstrated high-speed and low-latency properties in clear and coastal ocean water because of the relatively low attenuation 'window' for blue-green wavelengths from 450 nm to 550 nm. However, there are different attenuation coefficients for transmission in ocean water at different wavelengths, and the light transmission more seriously deteriorates with fluctuations in the water turbidity. Therefore, traditional UWOC using a single wavelength or coarse blue-green wavelengths has difficulty tolerating variations in water turbidity. Dense wavelength division multiplexing (WDM) technology provides sufficient communication channels with a narrow wavelength spacing and minimal channel crosstalk. Here, we improve the UWOC in clear and coastal ocean water using dense blue-green WDM. A cost-effective WDM emitter is proposed with directly modulated blue-green laser diodes. Dense wavelength beam combination and collimation are demonstrated in a 20-metre underwater channel from 490 nm to 520 nm. Demultiplexing with a minimum channel spacing of 2 nm is realized by an optical grating. Remarkably, our WDM results demonstrate an aggregate data rate exceeding 10 Gbit/s under diverse water turbidity conditions, with negligible crosstalk observed for each channel. This is the densest WDM implementation with a record channel spacing of 2 nm and the highest channel count for underwater blue-green light communications, providing turbidity-tolerant signal transmission in clear and coastal ocean water.

[Spatial and Temporal Distribution of Antibiotic Resistance Genes in Different River Sediments in Typical Cities: A Case Study of Shijiazhuang].

Rivers are important reservoirs of antibiotic resistance genes (ARGs). However, most current studies have focused on the temporal and spatial distribution, and data on the differences in the species and abundance of ARGs between urban and rural rivers is still lacking for certain areas. In view of this, two rural rivers and three urban rivers were selected in Shijiazhuang City. In both December 2020 and April 2021, sediments were collected at 15 sampling sites. Metagenomic sequencing technology was used to compare the differences in temporal-spatial variation for ARGs in sediments. The results showed that:① 162 and 79 ARGs were detected in urban (4 776 ±4 452) and rural rivers (1 043 ±632), respectively. The abundance and species of ARGs in urban rivers were higher than those in rural rivers. ② The relative abundances of sulfonamide (SAs,27 %), aminoglycoside (AGs,26 %), and multidrug (MDs,15 %) ARGs had the highest abundance in urban rivers, whereas the relative abundance of MDs ARGs was highest in rural rivers (65 %). On the whole, the complexity of ARGs in urban rivers was higher than that in rural rivers. ③ There was a significant positive correlation between SAs, AGs, MDs, tetracycline, phenicol, macrolides-lincosamids-streptogramins (MLS), ß-lactams, and diaminopyrimidine ARGs in urban rivers (P < 0.01); however, there was a significant negative correlation between glycopeptide ARGs and all types of ARGs (P < 0.05 and P < 0.01). There was a significant positive correlation between MDs and SAs ARGs in rural rivers (P < 0.05), but there was a significant negative correlation between amino aminocoumarin, peptide, rifamycin, and fosfomycin ARGs (P < 0.05 and P < 0.01). ④ For the temporal variation in urban rivers, 162 ARGs (4 776 ±4 452) and 148 ARGs (5 673 ±5 626) were detected in December and April, respectively. For the temporal variation in rural rivers, 79 species (1 043 ±632) and 46 species (467 ±183) were detected in December and April, respectively. ⑤ RDA analysis results showed that the spatial-temporal distributions of ARGs in urban and rural rivers were different. Correlation analysis showed that the ARGs in urban rivers were significantly correlated with the number of industrial enterprises, whereas the ARGs in rural rivers were significantly correlated with the output value of animal husbandry. In general, this study identified the main influencing factors for ARGs in different rivers and provided data support for ARGs risk management in different rivers.

Molecular Engineering of Methylated Sulfone-based Covalent Organic Frameworks for Back-reaction Inhibited Photocatalytic Overall Water Splitting.

Solar-to-hydrogen (H2) and oxygen (O2) conversion via photocatalytic overall water splitting (OWS) holds great promise for a sustainable fuel economy, but has been challenged by the backward O2 reduction reaction (ORR) due to its favored proton-coupled electron transfer (PCET) dynamics. Here, we report that molecular engineering by methylation inhibits the backward ORR of molecular photocatalysts and enables efficient OWS process. As demonstrated by a benchmark sulfone-based covalent organic framework (COF) photocatalyst, the precise methylation of its O2 adsorption sites effectively blocks electron transfer and increases the barrier for hydrogen intermediate desorption that cooperatively obstructs the PCET process of ORR. Methylation also repels electrons to the neighboring photocatalytic sulfone group that promotes the forward H2 evolution. The resultant DS-COF achieves an impressive inhibition of about 70% of the backward reaction and a three-fold enhancement of the OWS performance with a H2 evolution rate of 124.7 µmol h-1 g-1, ranking among the highest reported for organic photocatalysts. This work provides insights for engineering photocatalysts at the molecular level for efficient solar-to-fuel conversion.

Decoding the Expressions, Immune Relevance, and Prognostic Values of Ferroptosis Gene TMEM189: A Pan-Cancer Analysis.

BACKGROUND: TMEM189 is a recently discovered transmembrane protein involved in ether glycerophospholipid synthesis and ferroptosis regulation. However, its role in tumors are not well understood. OBJECTIVE: To elucidate the oncogenic effects and prognostic values of TMEM189 in tumors. METHODS: We performed a pan-cancer analysis of TMEM189 using various databases, bioinformatics and statistical tools, and tissue microarray analysis. RESULTS: TMEM189 is generally upregulated in tumors compared to normal tissues. High TMEM189 expression is linked to reduced promoter methylation. TMEM189 exhibits a negative correlation with immunogenic markers, immune cell infiltration, and expression of immune checkpoint genes (ICGs) in most cancers, implicating its immunosuppressive role in tumor microenvironments (TME). The interacting and similar genes with TMEM189 were involved in hotspot signaling pathways in pan-cancer. TMEM189 overexpression is usually associated with poor prognosis, especially an independent prognostic risk factor for BLCA, BRCA, LUAD, MESO, LIHC and SKCM. CONCLUSION: TMEM189 is overexpressed and exerts immunosuppressive effects in many tumors with a significant association with poor prognosis, suggesting its potential as a therapeutic target in cancer treatment.

Dietary ellagic acid therapy for CNS autoimmunity: Targeting on Alloprevotella rava and propionate metabolism.

BACKGROUND: Mediterranean diet rich in polyphenolic compounds holds great promise to prevent and alleviate multiple sclerosis (MS), a central nervous system autoimmune disease associated with gut microbiome dysbiosis. Health-promoting effects of natural polyphenols with low bioavailability could be attributed to gut microbiota reconstruction. However, its underlying mechanism of action remains elusive, resulting in rare therapies have proposed for polyphenol-targeted modulation of gut microbiota for the treatment of MS. RESULTS: We found that oral ellagic acid (EA), a natural polyphenol rich in the Mediterranean diet, effectively halted the progression of experimental autoimmune encephalomyelitis (EAE), the animal model of MS, via regulating a microbiota-metabolites-immunity axis. EA remodeled the gut microbiome composition and particularly increased the relative abundances of short-chain fatty acids -producing bacteria like Alloprevotella. Propionate (C3) was most significantly up-regulated by EA, and integrative modeling revealed a strong negative correlation between Alloprevotella or C3 and the pathological symptoms of EAE. Gut microbiota depletion negated the alleviating effects of EA on EAE, whereas oral administration of Alloprevotella rava mimicked the beneficial effects of EA on EAE. Moreover, EA directly promoted Alloprevotella rava (DSM 22548) growth and C3 production in vitro. The cell-free supernatants of Alloprevotella rava co-culture with EA suppressed Th17 differentiation by modulating acetylation in cell models. C3 can alleviate EAE development, and the mechanism may be through inhibiting HDAC activity and up-regulating acetylation thereby reducing inflammatory cytokines secreted by pathogenic Th17 cells. CONCLUSIONS: Our study identifies EA as a novel and potentially effective prebiotic for improving MS and other autoimmune diseases via the microbiota-metabolites-immunity axis. Video Abstract.

The influence of sleep disorders on perioperative neurocognitive disorders among the elderly: A narrative review.

This review comprehensively assesses the epidemiology, interaction, and impact on patient outcomes of perioperative sleep disorders (SD) and perioperative neurocognitive disorders (PND) in the elderly. The incidence of SD and PND during the perioperative period in older adults is alarmingly high, with SD significantly contributing to the occurrence of postoperative delirium. However, the clinical evidence linking SD to PND remains insufficient, despite substantial preclinical data. Therefore, this study focuses on the underlying mechanisms between SD and PND, underscoring that potential mechanisms driving SD-induced PND include uncontrolled central nervous inflammation, blood-brain barrier disruption, circadian rhythm disturbances, glial cell dysfunction, neuronal and synaptic abnormalities, impaired central metabolic waste clearance, gut microbiome dysbiosis, hippocampal oxidative stress, and altered brain network connectivity. Additionally, the review also evaluates the effectiveness of various sleep interventions, both pharmacological and nonpharmacological, in mitigating PND. Strategies such as earplugs, eye masks, restoring circadian rhythms, physical exercise, noninvasive brain stimulation, dexmedetomidine, and melatonin receptor agonists have shown efficacy in reducing PND incidence. The impact of other sleep-improvement drugs (e.g., orexin receptor antagonists) and methods (e.g., cognitive-behavioral therapy for insomnia) on PND is still unclear. However, certain drugs used for treating SD (e.g., antidepressants and first-generation antihistamines) may potentially aggravate PND. By providing valuable insights and references, this review aimed to enhance the understanding and management of PND in older adults based on SD.

Therapeutic Inhibition of LincRNA-p21 Protects Against Cardiac Hypertrophy.

BACKGROUND: Cardiac hypertrophy is an adaptive response to pressure overload aimed at maintaining cardiac function. However, prolonged hypertrophy significantly increases the risk of maladaptive cardiac remodeling and heart failure. Recent studies have implicated long noncoding RNAs in cardiac hypertrophy and cardiomyopathy, but their significance and mechanism(s) of action are not well understood. METHODS: We measured lincRNA-p21 RNA and H3K27ac levels in the hearts of dilated cardiomyopathy patients. We assessed the functional role of lincRNA-p21 in basal and surgical pressure-overload conditions using loss-of-function mice. Genome-wide transcriptome analysis revealed dysregulated genes and pathways. We labeled proteins in proximity to full-length lincRNA-p21 using a novel BioID2-based system. We immunoprecipitated lincRNA-p21-interacting proteins and performed cell fractionation, ChIP-seq (chromatin immunoprecipitation followed by sequencing), and co-immunoprecipitation to investigate molecular interactions and underlying mechanisms. We used GapmeR antisense oligonucleotides to evaluate the therapeutic potential of lincRNA-p21 inhibition in cardiac hypertrophy and associated heart failure. RESULTS: lincRNA-p21 was induced in mice and humans with cardiomyopathy. Global and cardiac-specific lincRNA-p21 knockout significantly suppressed pressure overload-induced ventricular wall thickening, stress marker elevation, and deterioration of cardiac function. Genome-wide transcriptome analysis and transcriptional network analysis revealed that lincRNA-p21 acts in trans to stimulate the NFAT/MEF2 pathway. Mechanistically, lincRNA-p21 is bound to the scaffold protein KAP1. lincRNA-p21 cardiac-specific knockout suppressed stress-induced nuclear accumulation of KAP1, and KAP1 knockdown attenuated cardiac hypertrophy and NFAT activation. KAP1 positively regulates pathological hypertrophy by physically interacting with NFATC4 to promote the overactive status of NFAT/MEF2 signaling. GapmeR antisense oligonucleotide depletion of lincRNA-p21 similarly inhibited cardiac hypertrophy and adverse remodeling, highlighting the therapeutic potential of inhibiting lincRNA-p21. CONCLUSIONS: These findings advance our understanding of the functional significance of stress-induced long noncoding RNA in cardiac hypertrophy and demonstrate the potential of lincRNA-p21 as a novel therapeutic target for cardiac hypertrophy and subsequent heart failure.