Platr3/NUDT21/NF-κB Axis Mediates P. gingivalis-Suppressed Cementoblast Mineralization.

Porphyromonas gingivalis (P. gingivalis) is one of the major pathogens causing periodontitis and apical periodontitis (AP). Long noncoding RNA (lncRNA) can regulate cellular mineralization and inflammatory diseases. The aim of this study was to investigate the role and mechanism of lncRNA in P. gingivalis-stimulated cementoblast mineralization. In vivo, C57BL/6 mice were divided into the healthy, the AP, and AP + P. gingivalis groups (n = six mice per group). Micro computed tomography, immunohistochemistry staining, and fluorescence in situ hybridization were used to observe periapical tissue. In vitro, cementoblasts were treated with osteogenic medium or P. gingivalis. Pluripotency associated transcript 3 (Platr3), interleukin 1 beta (IL1B), and osteogenic markers were analyzed by quantitative real-time polymerase chain reaction and western blot. RNA pull-down and RNA immunoprecipitation assays were used to detect proteins that bind to Platr3. RNA sequencing was performed in Platr3-silenced cementoblasts. In vivo, P. gingivalis promoted periapical tissue destruction and IL1B expression, but inhibited Platr3 expression. In vitro, P. gingivalis facilitated IL1B expression (P < 0.001), whereas suppressed the expression of Platr3 (P < 0.001) and osteogenic markers (P < 0.01 or 0.001). In contrast, Platr3 overexpression alleviated the repressive effect of P. gingivalis on cementoblast mineralization (P < 0.01 or 0.001). Furthermore, Platr3 bound to nudix hydrolase 21 (NUDT21) and regulated the nuclear factor-κB (NF-κB) signaling pathway. Knocking down NUDT21 suppressed osteogenic marker expression and activated the above signaling pathway. Collectively, the results elucidated that Platr3 mediated P. gingivalis-suppressed cementoblast mineralization through the NF-κB signaling pathway by binding to NUDT21.

The global burden of disease attributable to high body mass index in 204 countries and territories: Findings from 1990 to 2019 and predictions to 2035.

AIM: Our study aims to provide an updated estimate of age- and sex-specific deaths and disability-adjusted life years (DALYs) associated with high body mass index (BMI) from 1990 to 2019 at the global, regional and national levels, and to forecast the global burden of disease attributed to high BMI from 2020 to 2035. METHODS: We used the data for the number of deaths, DALYs, age-standardized rate (per 100 000 population), percentage change and population attributable fraction from the Global Burden of Disease Study 2019 (GBD 2019) to examine the disease burden attributable to high BMI. We further applied an autoregressive integrated moving average (ARIMA) model to predict the disease burden for the period 2020-2035. RESULTS: From 1990 to 2019, the deaths and DALYs attributable to high BMI increased by 148% and 155.86% for men, and by 111.67% and 121.78% for women, respectively. In 2019, high BMI directly accounted for 8.52% [95% uncertainty intervals (UI) 0.05, 0.12] of all-cause deaths and 5.89% (95% UI 0.04, 0.08) of global DALYs. The highest death rates were observed in men aged 65-69 and women aged 75-79. The highest DALY rates were observed in the age group of 60-64 for both sexes. In 2019, the highest age-standardized deaths and DALY rates were observed in the Central Asia region [163.15 (95% UI 107.72, 223.58) per 100 000 people] and the Oceania region [4643.33 (95% UI 2835.66, 6902.6) per 100 000 people], respectively. Fiji [319.08 (95% UI 213.77, 444.96) per 100 000 people] and Kiribati [10 000.58 (95% UI 6266.55, 14159.2) per 100 000 people] had the highest age-standardized deaths and DALY rates, respectively. In 2019, the highest age-standardized rates of high BMI-related deaths and DALYs were observed in the middle-high socio-demographic index quintile and in the middle socio-demographic index quintile. The age-standardized deaths and DALY rates attributable to high BMI are projected to increase in both sexes from 2020 to 2035. The death rates are projected to rise from 62.79 to 64.31 per 100 000 people, while the DALY rates are projected to rise from 1946 to 2099.54 per 100 000 people. CONCLUSIONS: High BMIs significantly contribute to the global disease burden. The projected rise in deaths and DALY rates attributable to high BMI by 2035 highlights the critical need to address the impact of obesity on public health. Our study provides policymakers with up-to-date and comprehensive information.

Rational Design of Liquid-Liquid Microdispersion Droplet Microreactors for the Controllable Synthesis of Highly Uniform and Monodispersed Dextran Microspheres.

Hydrogel microspheres are biocompatible materials widely used in biological and medical fields. Emulsification and stirring are the commonly used methods to prepare hydrogels. However, the size distribution is considerably wide, the monodispersity and the mechanical intensity are poor, and the stable operation conditions are comparatively narrow to meet some sophisticated applications. In this paper, a T-shaped stepwise microchannel combined with a simple side microchannel structure is developed to explore the liquid-liquid dispersion mechanism, interfacial evolution behavior, satellite droplet formation mechanism and separation, and the eventual successful synthesis of dextran hydrogel microspheres. The effect of the operation parameters on droplet and microsphere size is comprehensively studied. The flow pattern and the stable operation condition range are given, and mathematical prediction models are developed under three different flow regimes for droplet size prediction. Based on the stable operating conditions, a microdroplet-based method combined with UV light curing is developed to synthesize the dextran hydrogel microsphere. The highly uniform and monodispersed dextran microspheres with good mechanical intensity are synthesized in the developed microfluidic platform. The size of the microsphere could be tuned from 50 to 300 µm with a capillary number in the range of 0.006-0.742. This work not only provides a facile method for functional polymeric microsphere preparation but also offers important design guidelines for the development of a robust microreactor.

A Minimalist Iron Oxide Nanoprobe for the High-Resolution Depiction of Stroke by Susceptibility-Weighted Imaging.

The precise mapping of collateral circulation and ischemic penumbra is crucial for diagnosing and treating acute ischemic stroke (AIS). Unfortunately, there exists a significant shortage of high-sensitivity and high-resolution in vivo imaging techniques to fulfill this requirement. Herein, a contrast enhanced susceptibility-weighted imaging (CE-SWI) using the minimalist dextran-modified Fe3O4 nanoparticles (Fe3O4@Dextran NPs) are introduced for the highly sensitive and high-resolution AIS depiction under 9.4 T for the first time. The Fe3O4@Dextran NPs are synthesized via a simple one-pot coprecipitation method using commercial reagents under room temperature. It shows merits of small size (hydrodynamic size 25.8 nm), good solubility, high transverse relaxivity (r2) of 51.3 mM-1s-1 at 9.4 T, and superior biocompatibility. The Fe3O4@Dextran NPs-enhanced SWI can highlight the cerebral vessels readily with significantly improved contrast and ultrahigh resolution of 0.1 mm under 9.4 T MR scanner, enabling the clear spatial identification of collateral circulation in the middle cerebral artery occlusion (MCAO) rat model. Furthermore, Fe3O4@Dextran NPs-enhanced SWI facilitates the precise depiction of ischemia core, collaterals, and ischemic penumbra post AIS through matching analysis with other multimodal MR sequences. The proposed Fe3O4@Dextran NPs-enhanced SWI offers a high-sensitivity and high-resolution imaging tool for individualized characterization and personally precise theranostics of stroke patients.

A Chromosome-Level Genome Assembly and Annotation for the Oecanthus rufescens (Orthoptera: Oecanthidae).

Oecanthus is a genus of cricket known for its distinctive chirping and distributed across major zoogeographical regions worldwide. This study focuses on Oecanthus rufescens, and conducts a comprehensive examination of its genome through genome sequencing technologies and bioinformatic analysis. A high-quality chromosome-level genome of O. rufescens was successfully obtained, revealing significant features of its genome structure. The genome size is 877.9 Mb, comprising 10 pseudo-chromosomes and 70 other sequences, with a GC content of 41.38% and an N50 value of 157,110,771 bp, indicating a high level of continuity. BUSCO assessment results demonstrate the genome's integrity and quality are high (of which 96.8% are single-copy and 1.6% are duplicated). Comprehensive genome annotation was also performed, identifying approximately 310 Mb of repetitive sequences, accounting for 35.3% of the total genome sequence, and discovering 15,481 tRNA genes, 4,082 rRNA genes, and 1,212 other non-coding genes. Furthermore, 15,031 protein-coding genes were identified, with BUSCO assessment results showing that 98.4% (of which 96.3% are single-copy and 1.6% are duplicated) of the genes were annotated.

Enhanced decision technique for optimized crude oil pretreatment under disc spherical fuzzy Aczel Alsina aggregation information.

Crude oil, the backbone of modern industry, holds unparalleled significance as a global energy cornerstone. Unlocking its potential hinges on effective pretreatment techniques, ensuring purity, and maximizing efficiency. This study extends the established Spherical Fuzzy Set paradigm to explore the domain of Disc Spherical Fuzzy Sets (D-SFSs) in critical decision-making for crude oil preparation. Investigating D-SFSs within the Aczel Alsina norm, the research employs comparison rules, conversion rules, and distance metrics. Primary operations of the Aczel Alsina norm in D-SFSs are examined, laying the groundwork for introducing unique aggregation operations within this framework. The paper's primary aim is to propose a hybrid method, termed MEREC-SWARA-MARCOS-D-SFSs Multiple Attribute Group Decision Making, which integrates the aforementioned aggregation procedures. A case study on crude oil pretreatment validates the effectiveness of the proposed method. Furthermore, a comprehensive comparison with CoCoSo underscores the reliability of the method. This study represents a significant stride in enhancing decision-making by providing a robust framework to tackle complex situations, particularly in the critical domain of crude oil pretreatment.

Association between biological ageing and periodontitis: Evidence from a cross-sectional survey and multi-omics Mendelian randomization analysis.

AIM: To investigate the relationship and potential causality between biological ageing and periodontitis. MATERIALS AND METHODS: We obtained the National Health and Nutrition Examination Survey (NHANES) and genome-wide association study (GWAS) summary statistics as well as single-cell sequencing data. Multivariate regression analysis based on cross-sectional data, Mendelian randomization (MR) and multi-omics integration analysis were employed to explore the causal association and potential molecular mechanisms between biological ageing and periodontitis. Additionally, two-step MR mediation analysis explored the risk factors in biological ageing-mediated periodontitis. RESULTS: We analysed data from 3189 participants in the NHANES data and found that higher biological age was associated with increased risk of periodontitis. MR analyses revealed causal associations between biological age measures and periodontitis risk. Frailty (odds ratio [OR] = 2.08, 95% confidence interval [CI]: 1.04-4.18, p = .039) and GrimAge acceleration (OR = 1.16, 95% CI: 1.01-1.32, p = .033) were causally associated with periodontitis risk, and these results were validated in a large-scale meta-periodontitis GWAS dataset. Additionally, the risk effects of body mass index, waist circumference and lifetime smoking on periodontitis were partially mediated by frailty and GrimAge acceleration. CONCLUSIONS: Evidence from cross-sectional survey and MR analysis suggests that biological ageing increases the risk of periodontitis. Additionally, improving the associated risk factors can help prevent both ageing and periodontitis.

Constructing Orbital Coupling-Modulated Homogeneous Dual-Atom Fe-Fe Sites for Boosting Bidirectional Conversion of Polysulfides.

Homogeneous dual-atom catalysts (HDACs) have garnered significant attention for their potential to overcome the shuttling effect and sluggish reaction kinetics in lithium-sulfur (Li-S) batteries. However, modulating the electron structure of metal atomic orbitals for HDACs to dictate the catalytic activity toward polysulfides has remained meaningful but unexplored so far. Herein, an interfacial cladding strategy is developed to obtain a new type of dual-atom iron matrix with a unique FeN2P1-FeN2P1 coordination structure (Fe2@NCP). The 3d orbital electrons of the Fe centers are redistributed by incorporating phosphorus atoms into the first coordination sphere. The theoretical calculations disclose that the strong coupling between the Fe d orbital and the S p orbital exhibits an enhanced Fe-S bond and improved reactivity toward polysulfides. Moreover, the Fe2@NCP catalyst achieves robust adsorption ability toward Li2Sn (1 ≤ n ≤ 8) and significantly boosts bidirectional sulfur redox reaction kinetics by lowering the Li2S deposition/decomposition energy barriers. Consequently, the assembled Li-S batteries present a high retention ratio of 77.3% after 500 cycles at 1C. Furthermore, the Li-S pouch cell also exhibits good performance at 0.1C (80.2% retention over 100 cycles) for practical application with a sulfur loading of 4.0 mg/cm2. The outcome of this study will facilitate the design of homogeneous dual-atom catalysts for Li-S batteries.

Controlled release of manganese and magnesium ions by microsphere-encapsulated hydrogel enhances cancer immunotherapy.

Despite the considerable potential of immune checkpoint blockade (ICB) therapy in treating various cancer types, it faces several challenges, of which the constrained objective response rate and relatively short duration of response observed in patients with cancer are the most important. This study introduces an injectable temperature-sensitive hydrogel, Pluronic F-127 (PF-127)@MnCl2/ alginate microspheres (ALG-MS)@MgCl2, that enhances the therapeutic efficacy of programmed cell death-ligand 1 (PD-L1) in cancer cells. The hydrogel material used in this study facilitated the rapid release of a significant amount of manganese ions (Mn2+) and the gradual and sustained release of magnesium ions (Mg2+) within the tumor microenvironment. This staged release profile promotes an immune microenvironment conducive to the cytotoxicity of CD8+ T cells and natural killer cells, thereby enhancing the efficacy of ICB therapy. Furthermore, the PF-127@MnCl2/ALG-MS@MgCl2 composite hydrogel exhibits the ability to convert drug-resistant tumor ("cold tumor") with a low PD-L1 response to a "hot tumor" with a high PD-L1 response. In summary, the PF-127@MnCl2/ALG-MS@MgCl2 hydrogel manipulates the immune microenvironment through the precise discharge of Mg2+ and Mn2+, thus, augmenting the efficacy of ICB therapy.

m6A- and m5C- modified lncRNAs orchestrate the prognosis in cutaneous melanoma and m6A- modified LINC00893 regulates cutaneous melanoma cell metastasis.

BACKGROUND: As the most important modifications on the RNA level, N6-methyladenosine (m6A-) and 5-methylcytosine (m5C-) modification could have a direct influence on the RNAs. Long non-coding RNAs (lncRNAs) could also be modified by methylcytosine modification. Compared with mRNAs, the function of lncRNAs could be more potent to some extent in biological processes like tumorigenesis. Until now, rare reports have been done associated with cutaneous melanoma. Herein, we wonder if the m6A- and m5C- modified lncRNAs could influence the immune landscape and prognosis in melanoma, and we also want to find some lncRNAs which could directly affect the malignant behaviors of melanoma. METHODS: Systematically, we explored the expression pattern of m6A- and m5C- modified lncRNAs in melanoma from datasets including UCSC Xena and NCBI GEO, and the prognostic lncRNAs were selected. Then, according to the expression pattern of lncRNAs, melanoma samples from these datasets were divided into several subtypes. Prognostic model, nomogram survival model, drug sensitivity, GO, and KEGG pathway analysis were performed. Furthermore, among several selected lncRNAs, we identified one lncRNA named LINC00893 and investigated its expression pattern and its biological function in melanoma cell lines. RESULTS: We identified 27 m6A- and m5C- related lncRNAs which were significantly associated with survival, and we made a subtype analysis of melanoma samples based on these 27 lncRNAs. Among the two subtypes, we found differences of immune cells infiltration between these two subtypes. Then, LASSO algorithm was used to screen the optimized lncRNAs combination including ZNF252P-AS1, MIAT, FAM13A-AS1, LINC-PINT, LINC00893, AGAP2-AS1, OIP5-AS1, and SEMA6A-AS1. We also found that there was a significant correlation between the different risk groups predicted based on RS model and the actual prognosis. The nomogram survival model based on independent survival prognostic factors was also constructed. Besides, sensitivity to chemotherapeutic agents, GO and KEGG analysis were performed. In different risk groups, a total of 14 drug molecules with different distributions were obtained, which included AZD6482, AZD7762, AZD8055, camptothecin, dasatinib, erlotinib, gefitinib, gemcitabine, GSK269962A, nilotinib, rapamycin, and sorafenib. A total of 55 significantly related biological processes and 17 KEGG signaling pathways were screened. At last, we noticed that LINC00893 had a relatively lower expression in melanoma tissue and cell lines compared with adjacent tissues and epidermal melanocyte, and down-regulation of LINC00893 could promote the malignant behavior of melanoma cells in A875 and MV3. In these two melanoma cell lines, down-regulation of m6A-related molecules like YTHDF3 and METTL3 could promote the expression of LINC00893. CONCLUSION: We made an analysis of m6A- and m5C- related lncRNAs in melanoma samples and a prediction of these lncRNAs' role in prognosis, tumor microenvironment, immune infiltration, and clinicopathological features. We also found that LINC00893, which is potentially regulated by m6A modification, could serve as a tumor-suppressor in melanoma and play an inhibitory role in melanoma metastasis.

Ultrasound characteristics can predict response to biologics therapy in stricturing Crohn's disease.

BACKGROUND: Stricture is a common complication in Crohn's disease (CD). Accurate identification of strictures that poorly respond to biologic therapy is essential for making optimal therapeutic decisions. This study aimed to determine the association between ultrasound characteristics of strictures and their therapeutic outcomes. METHODS: Consecutive CD patients with symptomatic strictures scheduled for biologic therapy were retrospectively recruited at a tertiary hospital. Baseline intestinal ultrasound was conducted to assess stricture characteristics, including bowel wall thickness, length, stratification, vascularity, and creeping fat wrapping angle. Patients were followed-up for a minimum of one year, during which long-term outcomes including surgery, steroid-free clinical remission, and mucosal healing were recorded. Statistical analyses were performed. RESULTS: A total of 43 patients were enrolled. Strictures were located in the ileocecal region (39.5%), colon (37.2%), anastomosis (20.9%), and small intestine (2.3%). The median follow-up time was 17 months (IQR 7-25), with 27 (62.8%) patients undergoing surgery. On multivariant analysis, creeping fat wrapping angle > 180° (OR 6.2, 95% CI 1.1-41.1) and a high Limberg score (OR 2.3, 95% CI 1.4-6.0) were independent predictors of surgery, with an area under the curve of 0.771 (95% CI: 0.602-0.940), accuracy of 83.7%, sensitivity of 96.3%, and specificity of 62.5%. On Cox survival analysis, creeping fat > 180° was significantly associated with surgery (HR, 5.2; 95% CI, 1.2-21.8; P=0.03). Additionally, creeping fat was significantly associated with steroid-free clinical remission (P=0.015) and mucosal healing (P=0.06). CONCLUSION: Intestinal ultrasound characteristics can predict outcomes in patients with stricturing Crohn's disease who undertook biologic therapy.

Pulmonary interstitial lesions in pemphigus mouse model: Verifying pemphigus may not be only limited to skin and mucosa.

Interstitial lung disease (ILD) has been identified as a prevalent complication and significant contributor to mortality in individuals with pemphigus. In this study, a murine model of pemphigus was developed through the subcutaneous administration of serum IgG obtained from pemphigus patients, allowing for an investigation into the association between pemphigus and ILD. Pulmonary interstitial lesions were identified in the lungs of a pemphigus mouse model through histopathology, RT-qPCR and Sircol assay analyses. The severity of these lesions was found to be positively associated with the concentration of IgG in the injected serum. Additionally, DIF staining revealed the deposition of serum IgG in the lung tissue of pemphigus mice, indicating that the subcutaneous administration of human IgG directly impacted the lung tissue of the mice, resulting in damage. This study confirms the presence of pulmonary interstitial lesions in the pemphigus mouse model and establishes a link between pemphigus and ILD.

Intracranial aneurysms and abducent nerve palsy.

Background: Cranial nerve (CN) palsy may manifest as an initial presentation of intracranial aneurysms or due to the treatment. The literature reveals a paucity of studies addressing the involvement of the 6th CN in the presentation of cerebral aneurysms. Methods: Clinical patient data, aneurysmal characteristics, and CN 6th palsy outcome were retrospectively reviewed and analyzed. Results: Out of 1311 cases analyzed, a total of 12 cases were identified as having CN 6th palsy at the presentation. Eight out of the 12 were found in the unruptured aneurysm in the cavernous segment of the internal carotid artery (ICA). The other four cases of CN 6th palsy were found in association with ruptured aneurysms located exclusively at the posterior inferior cerebellar artery (PICA). For the full functional recovery of the CN 6th palsy, there was 50% documented full recovery in the eight cases of the unruptured cavernous ICA aneurysm. On the other hand, all four patients with ruptured PICA aneurysms have a full recovery of CN 6th palsy. The duration for recovery for CN palsy ranges from 1 to 5 months. Conclusion: The association between intracranial aneurysms and CN 6th palsy at presentation may suggest distinct patterns related to aneurysmal location and size. The abducent nerve palsy can be linked to unruptured cavernous ICA and ruptured PICA aneurysms. The recovery of CN 6th palsy may be influenced by aneurysm size, rupture status, location, and treatment modality.

EIF4A3-Induced Circ_0059914 Promoted Angiogenesis and EMT of Glioma via the miR-1249/VEGFA Pathway.

Gliomas are common brain tumors. Despite extensive research, the 5-year survival rate of glioma remains low. Many studies have reported that circular RNAs (circRNAs) play a role in promoting the malignant progression of glioma; however, the role of circ_0059914 in this process remains unclear. In this study, we aimed to investigate the function and underlying mechanism of circ_0059914 in glioma. Western blotting and qRT-PCR were used to determine the levels of circ_0059914, miR-1249, VEGFA, N-cadherin, vimentin, Snail, and EIF4A3. EDU and colony formation assays were conducted to evaluate cell proliferation. Transwell assays were used to explore cell migration and invasion and tube formation assays were used to analyze angiogenesis. RNA immunoprecipitation (RIP) and dual-luciferase reporter assays were used to explore the relationship between EIF4A3, circ_0059914, miR-1249, and VEGFA. A xenograft tumor assay was performed to determine the role of circ_0059914 in vivo. Circ_0059914 expression was upregulated in gliomas. Knockdown of gliomal circ_0059914 expression reduced the proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), angiogenesis, and growth of glioma cells in vivo. Circ_0059914 sponged miR-1249, and miR-1249 inhibition reversed the circ_0059914 knockdown-mediated effects in glioma cells. VEGFA was found to be a target gene of miR1249; overexpression of VEGFA reversed the effect of miR-1249 up-regulation in glioma. Finally, EIF4A3 increased the expression of circ_0059914. EIF4A3-induced circ_0059914 expression plays a role in promoting glioma via the miR-1249/VEGFA axis.

Histone deacetylase 6 as a novel promising target to treat cardiovascular disease.

Histone deacetylase 6 (HDAC6) belongs to a class of epigenetic targets that have been found to be a key protein in the association between tumors and cardiovascular disease. Recent studies have focused on the crucial role of HDAC6 in regulating cardiovascular diseases such as atherosclerosis, myocardial infarction, myocardial hypertrophy, myocardial fibrosis, hypertension, pulmonary hypertension, and arrhythmia. Here, we review the association between HDAC6 and cardiovascular disease, the research progress of HDAC6 inhibitors in the treatment of cardiovascular disease, and discuss the feasibility of combining HDAC6 inhibitors with other therapeutic agents to treat cardiovascular disease.

Management of patient with Fusobacterim nucletum related pleural empyema: intrapleural antibiotic therapy can be considered for salvage therapy.

Pleural empyema can lead to significant morbidity and mortality despite chest drainage and antibiotic treatment, necessitating novel and minimally invasive interventions. Fusobacterium nucleatum is an obligate anaerobe found in the human oral and gut microbiota. Advances in sequencing and puncture techniques have made it common to detect anaerobic bacteria in empyema cases. In this report, we describe the case of a 65-year-old man with hypertension who presented with a left-sided encapsulated pleural effusion. Initial fluid analysis using metagenomic next-generation sequencing (mNGS) revealed the presence of Fusobacterium nucleatum and Aspergillus chevalieri. Unfortunately, the patient experienced worsening pleural effusion despite drainage and antimicrobial therapy. Ultimately, successful treatment was achieved through intrapleural metronidazole therapy in conjunction with systemic antibiotics. The present case showed that intrapleural antibiotic therapy is a promising measure for pleural empyema.

Hydrogen combined with tetrandrine attenuates silica-induced pulmonary fibrosis via suppressing NF-kappaB/NLRP3 signaling pathway-mediated epithelial mesenchymal transition and inflammation.

Silicosis is a progressive disease characterized by interstitial fibrosis resulting from inhalation of silica particles, and currently lacks specific treatment. Hydrogen (H2) has demonstrated antioxidative, anti-inflammatory, and anti-fibrotic properties, yet its efficacy in treating silicosis remains unexplored. In this study, rats exposed to silica were administered interventions of H2 combined with tetrandrine, and euthanized at 14, 28, and 56 days post-intervention. Lung tissues and serum samples were collected for analysis. Histological examination, MDA assay, enzyme-linked immunosorbent assay, hydroxyproline assay, and Western blotting were employed to assess the impact of H2 combined with tetrandrine on pulmonary fibrosis. The results revealed that this combination significantly alleviated inflammation in silicosis-afflicted rats, effectively suppressed levels of MDA, TNF-α, and IL-1ß expression, and inhibited epithelial-mesenchymal transition (EMT), thereby ameliorating pulmonary fibrosis. Notably, protein expression level of E-cadherin was increased，however protein expression levels of vimentin and α-SMA were reduced, and TGF-ß were reduced, alongside a significant decrease in hydroxyproline content. Furthermore, H2 combined with tetrandrine downregulated protein expression of NF-κB p65, NF-κB p-p65, Caspase-1, ASC, and NLRP3. These findings substantiate the hypothesis that H2 combined with tetrandrine mitigates inflammation associated with silicosis and suppresses the EMT process to ameliorate fibrosis via the NF-κB/NLRP3 signaling pathway. However, the pressure of airway opening was not assessed in this study and dynamic readings of lung physiological function were not obtained, which is a major limitation of this study.

The Structure of Digestive Tract Coordinating Digestion and Respiration in an Air-Breathing Weatherloach, Misgurnus anguillicaudatus.

To clarify how the digestive tract of the weatherloach, Misgurnus anguillicaudatus, serves a dual function of digestion and respiration simultaneously, the histological structures of its digestive tract, the passage of digesta and air passing through its intestine and the rate of intestinal evacuation have been studied. The results indicate that the digestive tract is divided into five functional regions, i.e., esophagus, anterior intestine, middle intestine, posterior intestine and rectum. The diverse intestinal structures have the specialized function of coordinating digestion and respiration. An X-ray barium meal examination showed in the normal breathing state, the contents of the intestine are diffusely semifluid, and air is distributed as bubbles in the dorsal intestine 2 h after feeding. After 5 h, the contents accumulated in the mid and posterior intestine, and gas flowed above the contents as bundles. After 8 h, the intestinal food was basically evacuated. In the intestinal air-breathing restricted group, the contents of the intestine remained diffuse, and a large number of digesta entered and remained in the rectum after 5 h. After the inhibition was relieved, the contents of the rectum were rapidly discharged. Measurement of the intestinal evacuation rate in the intestine showed that the evacuation of the intestinal contents lagged behind that of the normal group in the air-breathing restricted group. Compared to the normal state and inhibited GAB (gastrointestinal air breathing), we could deduce that GAB could promote the movement of the intestine.

Transcriptomic Analyses Reveal the Effects of Walnut Kernel Cake on Adipose Deposition in Pigs.

With the rising cost of animal feed protein, finding affordable and effective substitutes is crucial. Walnut kernel cake, a polyphenol-, fiber-, protein- and fat-rich byproduct of walnut oil extraction, has been underexplored as a potential protein replacement in pig feed. In this study, we found that feeding large Diqing Tibetan pigs walnut kernel cake promoted adipose deposition and improved pork quality during pig growth. Transcriptome analysis revealed the upregulation of genes ANGPTL8, CCNP, ETV4, and TRIB3, associated with adipose deposition. Pathway analysis highlighted enrichment in adipose deposition-related pathways, including PPAR, insulin, PI3K-Akt, Wnt, and MAPK signaling. Further analysis identified DEGs (differentially expressed genes) positively correlated with adipose-related traits, such as PER2 and PTGES. Single-cell transcriptome data pointed to the specific expression of CD248 and PTGES in adipocyte progenitor/stem cells (APSCs), pivotal for adipocyte differentiation and adipose deposition regulation. This study demonstrates walnut kernel cake's potential to substitute soybean cake in pig feed, providing high-quality protein and promoting adipose deposition. It offers insights into feed protein replacement, human functional food, fat metabolism, and related diseases, with marker genes and pathways supporting pig breeding and pork quality improvement.

Penetrative Ionic Organic Molecular Cage Nanozyme for the Targeted Treatment of Keratomycosis.

Keratomycosis, caused by pathogenic fungi, is an intractable blinding eye disease. Corneal penetration is an essential requirement for conventional antifungal medications to address keratomycosis. Due to the distinctive anatomical and physiological structure of the cornea, the therapeutic efficacy is hampered by the inadequate penetration capacity. Despite the emergence of diverse antifungal drug delivery systems and advanced antifungal nanomaterials, it has remained challenging to achieve corneal penetration over the past decade. This study fabricates a penetrative ionic organic molecular cage-based nanozyme (OMCzyme) for treating keratomycosis. The synthesis of OMCzyme involved two steps. Initially, the ionic OMC is synthesized by a [2+3] cycloimination reaction of triformylphloroglucinol and 2,3-diaminopropionic acid. Subsequently, OMCzyme is fabricated by coordination of Fe2⁺ with carboxyl anions and phenolic hydroxyls in the organic cage, and further deposition of silver nanoparticles on the surface of OMC-Fe complex. The as-prepared OMCzyme demonstrates excellent water dispersion, peroxidase-like activity, in vitro and in vivo biocompatibility, and corneal penetration. Notably, the nanozyme displays targeted antifungal activity, effectively combating Fusarium solani with negligible cytotoxicity toward human corneal epithelial cells. The hybrid mimic is further demonstrated to be effective in treating keratomycosis in mice, indicating the potential of OMCzyme for curing fungal infectious diseases.