Fundus morphological characteristics assesment in high myopia patients with or without posterior scleral staphyloma by optical coherence tomography.

OBJECTIVE: To observe the morphological characteristics of posterior scleral staphyloma (PSS) with or without macular retinoschisis (MRS) using optical coherence tomography (OCT). Additionally, the incidence and severity of other pathologic myopic maculopathy associated with posterior scleral staphyloma was also evaluated. METHODS: General information and OCT imaging data from 440 patients with posterior scleral staphyloma (PSS) and the PSS curvature > 20×10-3 µm-1 were collected. These patients visited the Department of Ophthalmology at the First Affiliated Hospital of Harbin Medical University from January 2013 to June 2021. The obtained OCT images of PSS were analyzed using the Image J software to measure the curvature along the Bruch's membrane. The measured curvature was divided into four levels using the quartile method. The classification of macular retinoschisis (MRS) was based on the anatomical structure of the retina and the location of macular retinoschisis. Patients with PSS accompanied by MRS were assigned to the MRS group, while PSS patients without MRS were assigned to the non-MRS group. Additionally, typical OCT changes in other pathologic myopic maculopathy diseases, such as myopic choroidal neovascularization (mCNV), myopic traction maculopathy (MTM), and myopic foveoschisis (MF), were recorded and evaluated. RESULTS: A total of 615 eyes (328 right eyes, 287 left eyes) from 440 patients (80 males and 360 females) were recruited in this study. The MRS group consisted of 159 patients (36.1%) with 190 eyes (30.9%), while the non-MRS group consisted of 281 patients (63.9%) with 425 eyes (69.1%). Both groups had a significantly higher proportion of female patients compared to male patients, and the right eye was more commonly affected than the left eye. In the MRS group, the prevalence of MRS increased progressively with the severity of PSS. Among the common posterior pole diseases, epiretinal membrane had the highest prevalence (33.2%), while lamellar macular hole had the lowest prevalence (5.3%). In the non-MRS group, the proportion of PSS in each group decreased progressively (except for an equal prevalence in the third and fourth levels) with increasing severity of PSS. Among the common posterior pole diseases, choroidal neovascularization had the highest prevalence (41.4%), while lamellar macular hole had the lowest prevalence (6.5%). When comparing the two groups, there were no significant differences in age, gender, and eye distribution. The MRS group had a higher prevalence of macular schisis, retinal detachment, and dome-shaped macula (17.9%, 14.2%, 14.8%) compared to the non-MRS group (11.3%, 9.2%, 9.6%). The non-MRS group had a significantly higher prevalence of choroidal neovascularization (41.4%) compared to the MRS group (12.6%), while there were no significant differences in the prevalence of epiretinal membrane and lamellar macular hole between the two groups. CONCLUSION: The prevalence of MRS increased progressively with the severity of PSS, and the MRS occurrence was positively correlated with PSS, which indicated that PSS may lead to MRS, while the proportion of PSS in each group decreases gradually with the severity of PSS in the non-MRS group decreased progressively (except for an equal prevalence in the third and fourth levels). In the MRS group, outer macular retinoschisiss were most relevant to posterior scleral staphyloma, and the prevalence of macular holes and retinal detachments was higher in the MRS group compared to the non-MRS group, indicating that MRS may further turn into complications such as macular holes and retinal detachments, which can significantly affect vision or lead to blindness. The prevalence of choroidal neovascularization (CNV) was significantly higher in the non-MRS group compared to the MRS group, suggesting that PSS with lower severity is more prone to develop into CNV. Dome-shaped macula (DSM) seems to play a protective role in the development of pathologic myopia, and abnormal changes in posterior scleral staphyloma curvature may be an important factor affecting the development and shape of DSM.

Machine Learning Identification of Nutrient Intake Variations across Age Groups in Metabolic Syndrome and Healthy Populations.

This study undertakes a comprehensive examination of the intricate link between diet nutrition, age, and metabolic syndrome (MetS), utilizing advanced artificial intelligence methodologies. Data from the National Health and Nutrition Examination Survey (NHANES) spanning from 1999 to 2018 were meticulously analyzed using machine learning (ML) techniques, specifically extreme gradient boosting (XGBoost) and the proportional hazards model (COX). Using these analytic methods, we elucidated a significant correlation between age and MetS incidence and revealed the impact of age-specific dietary patterns on MetS. The study delineated how the consumption of certain dietary components, namely retinol, beta-cryptoxanthin, vitamin C, theobromine, caffeine, lycopene, and alcohol, variably affects MetS across different age demographics. Furthermore, it was revealed that identical nutritional intakes pose diverse pathogenic risks for MetS across varying age brackets, with substances such as cholesterol, caffeine, and theobromine exhibiting differential risks contingent on age. Importantly, this investigation succeeded in developing a predictive model of high accuracy, distinguishing individuals with MetS from healthy controls, thereby highlighting the potential for precision in dietary interventions and MetS management strategies tailored to specific age groups. These findings underscore the importance of age-specific nutritional guidance and lay the foundation for future research in this area.

Conversion of Phosphogypsum into Porous Calcium Silicate Hydrate for the Removal and Recycling of Pb(II) and Cd(II) from Wastewater.

The discharge of lead and cadmium wastewater, along with the pollution caused by phosphogypsum, represents a particularly urgent environmental issue. This study employed a straightforward hydrothermal method to convert phosphogypsum into porous calcium silicate hydrate (P-CSH), which was then used to remove and recover Pb(II) and Cd(II) from wastewater. The adsorption capacities of P-CSH for Pb(II) and Cd(II) were notably high at 989.3 mg/g and 290.3 mg/g, respectively. The adsorption processes adhered to the pseudo-second-order kinetics model and the Langmuir isotherm model. Due to identical adsorption sites on P-CSH for both Pb(II) and Cd(II), competitive interaction occurred when both ions were present simultaneously. Additionally, the adsorption efficacy was minimally impacted by the presence of common coexisting cations in wastewater. The dominant mechanisms for removing Pb(II) and Cd(II) via P-CSH were chemical precipitation and surface complexation. Moreover, the adsorbed heavy metals were efficiently separated and reclaimed from the wastewater through a stepwise desorption process. The primary components of the residue from stepwise desorption were quartz and amorphous SiO2. Following dissolution via pressurized alkaline leaching, this residue could be recycled for synthesizing P-CSH. This research offered a new strategy for the resourceful use of phosphogypsum and heavy metal wastewater.

Investigation on the control of inclusions and tensile strength in Ce-treated P110-grade oil casing steel.

This research added rare Earth elements Ce to the P110-grade oil casing steel to reveal their influence on the inclusions and tensile properties. The content of cerium in the steel varied from 0 to 452 ppm. Based on the classical thermodynamic calculation, the predominance diagram of Re-containing inclusions in P110-grade steel was obtained. The evolution route of the inclusions composition with the increasing cerium content in the steel was xCaO⋅yAl2O3 → Al2O3-CeAlO3 → Ce2O3-CeAlO3 → Ce2O3-Ce2O2S → Ce2O2S, which agreed well with the thermodynamic analysis. As the cerium content at 235 ppm, the size of Ce containing inclusions has a minimal size at 2.82 µm. Suitable Ce content can modify the big-size xCaO⋅yAl2O3 inclusions into small-size Re-containing inclusions. The results demonstrate that the tensile performance of this steel can be improved as the cerium content increases from 0 to 235 ppm. However, once the cerium content exceeds 235 ppm, further increases in cerium content led to a decline in performance. The experimental results shows that the presence of large-sized Ce2O2S inclusions and the change of microstructure, will lead to the decrease in tensile performance.

HMGA1 sensitizes esophageal squamous cell carcinoma to mTOR inhibitors through the ETS1-FKBP12 axis.

Esophageal carcinoma is amongst the prevalent malignancies worldwide, characterized by unclear molecular classifications and varying clinical outcomes. The PI3K/AKT/mTOR signaling, one of the frequently perturbed dysregulated pathways in human malignancies, has instigated the development of various inhibitory agents targeting this pathway, but many ESCC patients exhibit intrinsic or adaptive resistance to these inhibitors. Here, we aim to explore the reasons for the insensitivity of ESCC patients to mTOR inhibitors. We assessed the sensitivity to rapamycin in various ESCC cell lines by determining their respective IC50 values and found that cells with a low level of HMGA1 were more tolerant to rapamycin. Subsequent experiments have supported this finding. Through a transcriptome sequencing, we identified a crucial downstream effector of HMGA1, FKBP12, and found that FKBP12 was necessary for HMGA1-induced cell sensitivity to rapamycin. HMGA1 interacted with ETS1, and facilitated the transcription of FKBP12. Finally, we validated this regulatory axis in in vivo experiments, where HMGA1 deficiency in transplanted tumors rendered them resistance to rapamycin. Therefore, we speculate that mTOR inhibitor therapy for individuals exhibiting a reduced level of HMGA1 or FKBP12 may not work. Conversely, individuals exhibiting an elevated level of HMGA1 or FKBP12 are more suitable candidates for mTOR inhibitor treatment.

DNA Image Cytometry for Screening the Carcinogenetic Risk of Oral Potential Malignant Disorders.

Background: Oral Submucosal Fibrosis (OSF) and Oral Leukoplakia (OLK) are well-known oral potentially malignant disorders, and cases of Oral Submucosal Fibrosis concomitant Oral Leukoplakia (OSF+OLK) are now being reported clinically. DNA image cytometry is an objective and non-invasive method for monitoring the risk of precancerous lesions in the oral cavity. Methods: A total of 111 patients with clinically characterized oral mucosal lesions underwent simultaneous and independent histopathological and DNA imaging cytometry assessments. Clinical data were also collected for each patient. Results: The frequency of DNA content abnormality was higher in the tongue than in other oral sites (P = 0.003) for OLK. The frequency of DNA content abnormality was higher in the tongue than in other oral sites (P = 0.035) for OSF+OLK. The differences of DNA content abnormality in age, sex, dietary habit, smoking, and alcohol intake were not observed in OLK and OSF+OLK. The study indicates an association between DNA content abnormality and pathological examination in OSF+OLK ( χ2 test, P = 0.007). OLK showed higher sensitivity and specificity than OSF, while the sensitivity and specificity of OSF+OLK are higher than OLK only and OSF only. Conclusion: DNA image cytometry can be utilized as an adjunctive device for the initial detection of oral potentially malignant disorders that require further clinical management.

HMGA1 drives chemoresistance in esophageal squamous cell carcinoma by suppressing ferroptosis.

Chemotherapy is a primary treatment for esophageal squamous cell carcinoma (ESCC). Resistance to chemotherapeutic drugs is an important hurdle to effective treatment. Understanding the mechanisms underlying chemotherapy resistance in ESCC is an unmet medical need to improve the survival of ESCC. Herein, we demonstrate that ferroptosis triggered by inhibiting high mobility group AT-hook 1 (HMGA1) may provide a novel opportunity to gain an effective therapeutic strategy against chemoresistance in ESCC. HMGA1 is upregulated in ESCC and works as a key driver for cisplatin (DDP) resistance in ESCC by repressing ferroptosis. Inhibition of HMGA1 enhances the sensitivity of ESCC to ferroptosis. With a transcriptome analysis and following-up assays, we demonstrated that HMGA1 upregulates the expression of solute carrier family 7 member 11 (SLC7A11), a key transporter maintaining intracellular glutathione homeostasis and inhibiting the accumulation of malondialdehyde (MDA), thereby suppressing cell ferroptosis. HMGA1 acts as a chromatin remodeling factor promoting the binding of activating transcription factor 4 (ATF4) to the promoter of SLC7A11, and hence enhancing the transcription of SLC7A11 and maintaining the redox balance. We characterized that the enhanced chemosensitivity of ESCC is primarily attributed to the increased susceptibility of ferroptosis resulting from the depletion of HMGA1. Moreover, we utilized syngeneic allograft tumor models and genetically engineered mice of HMGA1 to induce ESCC and validated that depletion of HMGA1 promotes ferroptosis and restores the sensitivity of ESCC to DDP, and hence enhances the therapeutic efficacy. Our finding uncovers a critical role of HMGA1 in the repression of ferroptosis and thus in the establishment of DDP resistance in ESCC, highlighting HMGA1-based rewiring strategies as potential approaches to overcome ESCC chemotherapy resistance. Schematic depicting that HMGA1 maintains intracellular redox homeostasis against ferroptosis by assisting ATF4 to activate SLC7A11 transcription, resulting in ESCC resistance to chemotherapy.

Discovery of astragaloside IV against high glucose-induced apoptosis in retinal ganglion cells: Bioinformatics and in vitro studies.

OBJECTIVE: To examine the therapeutic mechanism of astragaloside IV (AS-IV) in the management of retinal ganglion cell (RGC) injury induced by high glucose (HG), a comprehensive approach involving the integration of network pharmacology and conducting in vitro and in vivo experiments was utilized. METHODS: A rat model of diabetic retinopathy (DR) injury was created by administering streptozotocin through intraperitoneal injection. Additionally, a model of RGC injury induced by HG was established using a glucose concentration of 0.3 mmol/mL. Optical coherence tomography (OCT) images were captured 8 weeks after the injection of AS-IV. AS-IV and FBS were added to the culture medium and incubated for 48 h. The viability of cells was assessed using a CCK-8 assay, while the content of reactive oxygen species (ROS) was measured using DCFH-DA. Apoptosis was evaluated using Annexin V-PI. To identify the targets of AS-IV, hyperglycemia, and RGC, publicly available databases were utilized. The Metascape platform was employed for conducting GO and KEGG enrichment analyses. The STRING database in conjunction with Cytoscape 3.7.2 was used to determine common targets of protein-protein interactions (PPIs) and to identify the top 10 core target proteins in the RGC based on the MCC algorithm. qRT-PCR was used to measure the mRNA expression levels of the top10 core target proteins in RGCs. RESULTS: OCT detection indicated that the thickness of the outer nucleus, and inner and outer accessory layers of the retina increased in the AS-IV treated retina compared to that in the DM group but decreased compared to that in the CON group. Coculturing RGC cells with AS-IV after HG induction resulted in a significant increase in cell viability and a decrease in ROS and apoptosis, suggesting that AS-IV can reduce damage to RGC cells caused by high glucose levels by inhibiting oxidative stress. There were 14 potential targets of AS-IV in the treatment of RGC damage induced by high glucose levels. The top 10 core target proteins identified by the MCC algorithm were HIF1α, AKT1, CTNNB1, SMAD2, IL6, SMAD3, IL1ß, PPARG, TGFß1, and NOTCH3. qRT-PCR analysis showed that AS-IV could upregulate the mRNA expression levels of SMAD3, TGF-ß1, and NOTCH3, and downregulate the mRNA expression levels of HIF1α, AKT1, CTNNB1, SMAD2, SMAD3, and IL-1ß in high glucose-induced RGC cells. CONCLUSION: The findings of this study validate the efficacy of astragaloside IV in the treatment of DR and shed light on the molecular network involved. Specifically, HIF1α, AKT1, CTNNB1, SMAD2, SMAD3, and IL-1ß were identified as the crucial candidate molecules responsible for the protective effects of astragaloside IV on RGCs.

Bioinformatics-based Study on the Effects of Umbilical Cord Mesenchymal Stem Cells on the Aging Retina.

BACKGROUND: Retinal aging is one of the common public health problems caused by population aging and has become an important cause of acquired vision loss in adults. The aim of this study was to determine the role of human umbilical cord mesenchymal stem cells (hUCMSCs) in delaying retinal ganglion cell (RGC) aging and part of the network of molecular mechanisms involved. METHODS: A retinal ganglion cell senescence model was established in vitro and treated with UCMSC. Successful establishment of the senescence system was demonstrated using ß- galactosidase staining. The ameliorative effect of MSC on senescence was demonstrated using CCK8 cell viability and Annexin V-PI apoptosis staining. The relevant targets of RGC, MSC, and senescence were mainly obtained by searching the GeneCards database. The protein interaction network among the relevant targets was constructed using the String database and Cytoscape, and 10 key target genes were calculated based on the MCC algorithm, based on which Gene ontologies (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were performed. Changes in relevant target genes were detected using real-time fluorescence quantitative PCR and the mechanism of action of UCMSC was determined by RNA interference. RESULTS: ß-galactosidase staining showed that UCMSC significantly reduced the positive results of RGC. The retinal aging process was alleviated. The bioinformatics screen yielded 201 shared genes. 10 key genes were selected by the MCC algorithm, including vascular endothelial growth factor A (VEGFA), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), albumin (ALB), interleukin- 6 (IL6), tumor necrosis factor (TNF), tumor protein P53 (TP53), insulin (INS), matrix metalloproteinase 9 (MMP9), epidermal growth factor (EGF), interleukin-1ß (IL1B), and enrichment to related transferase activity and kinase activity regulated biological processes involved in oxidative stress and inflammation related pathways. In addition, PCR results showed that all the above molecules were altered in expression after UCMSC involvement. CONCLUSION: This experiment demonstrated the role of UCMSC in delaying retinal ganglion cell senescence and further elucidated that UCMSC may be associated with the activation of VEGFA, TP53, ALB, GAPDH, IL6, IL1B, MMP9 genes and the inhibition of INS, EGF, and TNF in delaying retinal senescence.

Phenolylazoindole scaffold for facilely synthesized and bis-functional photoswitches combining controllable fluorescence and antifungal properties using theoretical methods.

Functionalization is a major challenge for the application of photoswitches. With the aim to develop novel bis-functional azo photoswitches with stationary photophysical properties, a series of phenolylazoindole derivatives were designed, synthesized, and characterized via NMR spectroscopy studies and high-resolution mass spectrometry (HRMS). Herein, UV/Vis and 1H NMR spectra revealed that the photostationary state (PSS) proportions for PSScis and PSStrans were 76-80% and 68-81%, respectively. Furthermore, the thermal half-lives (t1/2) of compounds A2-A4 and B2 ranged from 0.9 to 5.3 h, affected by the diverse substituents at the R1 and R2 positions. The results indicated that azo photoswitches based on the phenolylazoindole scaffold had stationary photophysical properties and wouldn't be excessively affected by modifying the functional groups. Compounds A4 and B2, which were modified with an aryl group, also exhibited fluorescence emission properties (the quantum yields of A4 and B2 were 2.32% and 13.34%) through the modification of the flexible conjugated structure (benzene) at the R2 position. Significantly, compound C1 was obtained via modification with a pharmacophore in order to acquire antifungal activities against three plant fungi, Rhizoctonia solani (R. solani), Botrytis cinerea (B. cinerea), and Fusarium graminearum (F. graminearum). Strikingly, the inhibitory activity of the cis-isomer of compound C1towards R. solani (53.3%) was significantly better than that of the trans-isomer (34.2%) at 50 µg mL-1. In order to further reveal the antifungal mechanism, molecular docking simulations demonstrated that compound C1 effectively integrates into the cavity of succinate dehydrogenase (SDH); the optically controlled cis-isomer showed a lower binding energy with SDH than that of the trans-isomer. This research confirmed that phenolylazoindole photoswitches can be appropriately applied as molecular regulatory devices and functional photoswitch molecules via bis-functionalization.

Tibetan tea consumption prevents obesity by modulating the cellular composition and metabolic reprogramming of white adipose tissue.

Obesity, a global health concern, is linked with numerous metabolic and inflammatory disorders. Tibetan tea, a traditional Chinese beverage rich in theabrownin, is investigated in this study for its potential anti-obesity effects. Our work demonstrates that Tibetan tea consumption in C57BL/6J mice significantly mitigates obesity-related phenotypic changes without altering energy intake. Computational prediction revealed that Tibetan tea consumption reconstructs gene expression in white adipose tissue (WAT), promoting lipid catabolism and thereby increasing energy expenditure. We also note that Tibetan tea suppresses inflammation in WAT, reducing adipocyte hyperplasia and immune cell infiltration. Furthermore, Tibetan tea induces profound metabolic reprogramming, influencing amino acid metabolic pathways, specifically enhancing glutamine synthesis, which in turn suppresses pro-inflammatory chemokine production. These findings highlight Tibetan tea as a potential candidate in obesity prevention, providing a nuanced understanding of its capacity to modulate the cellular composition and metabolic landscape of WAT.

Effects of different cooking methods on proximate composition, digestion characteristics, and antioxidant activity of Lentinus edodes.

Lentinus edodes (SM) are highly appreciated by the food industry together with consumers for nutrition and flavour. It is hypothesized the results of our study can indicate to the suitable cooking method for maximal nutrient retention, this study investigated the effects of six cooking methods on the proximate composition, digestive properties, and antioxidant activities of SM in vitro simulated digestion. The results revealed that the ash and protein contents of cooked samples were reduced excluding steaming and roasting, and likewise minerals during deep-frying and boiling (e.g., Mg from 1080.07 to 629.03 mg/kg, deep-frying). A conspicuous rise in fat and energy was found in deep-frying and stir-frying. Steaming retained more reducing sugar (3.80 mg/mL). Roasting improved bioaccessibility of most amino acids (e.g., 82.61%, Asp). Using oil as a medium was associated with higher antioxidant activities using water. Steaming and roasting were better for preserving the nutrient composition of cooked Lentinus edodes.

The Microbial Tryptophan Metabolite Contributes to the Remission of Salmonella typhimurium Infection in Mice.

Salmonella enterica serovar Typhimurium (S. Tm) causes severe foodborne diseases. Interestingly, gut microbial tryptophan (Trp) metabolism plays a pivotal role in such infections by a yet unknown mechanism. This study aimed to explore the impact of Trp metabolism on S. Tm infection and the possible mechanisms involved. S. Tm-infected C57BL6/J mice were used to demonstrate the therapeutic benefits of the Bacillus velezensis JT3-1 (B. velezensis/JT3-1) strain or its cell-free supernatant in enhancing Trp metabolism. Targeted Trp metabolomic analyses indicated the predominance of indole-3-lactic acid (ILA), an indole derivative and ligand for aryl hydrocarbon receptor (AHR). Based on the 16S amplicon sequencing and correlation analysis of metabolites, we found that B. velezensis supported the relative abundance of Lactobacillus and Ligilactobacillus in mouse gut and showed positive correlations with ILA levels. Moreover, AHR and its downstream genes (especially IL-22) significantly increased in mouse colons after B. velezensis or cell-free supernatant treatment, suggesting the importance of AHR pathway activation. In addition, ILA was found to stimulate primary mouse macrophages to secrete IL-22, which was antagonized by CH-223191. Furthermore, ILA could protect mice from S. Tm infection by increasing IL-22 in Ahr+/- mice, but not in Ahr-/- mice. Finally, Trp-rich feeding showed amelioration of S. Tm infection in mice, and the effect depended on gut microbiota. Taken together, these results suggest that B. velezensis-associated ILA contributes to protecting mice against S. Tm infection by activating the AHR/IL-22 pathway. This study provides insights into the involvement of microbiota-derived Trp catabolites in protecting against Salmonella infection.

Akkermansia muciniphila protects the intestine from irradiation-induced injury by secretion of propionic acid.

Intestinal dysbiosis frequently occurs in abdominal radiotherapy and contributes to irradiation (IR)-induced intestinal damage and inflammation. Akkermansia muciniphila (A. muciniphila) is a recently characterized probiotic, which is critical for maintaining the dynamics of the intestinal mucus layer and preserving intestinal microbiota homeostasis. However, the role of A. muciniphila in the alleviation of radiation enteritis remains unknown. In this study, we reported that the abundance of A. muciniphila was markedly reduced in the intestines of mice exposed to abdominal IR and in the feces of patients who received abdominal radiotherapy. Abundance of A. muciniphila in feces of radiotherapy patients was negatively correlated with the duration of diarrhea in patients. Administration of A. muciniphila substantially mitigated IR-induced intestinal damage and prevented mouse death. Analyzing the metabolic products of A. muciniphila revealed that propionic acid, a short-chain fatty acid secreted by the microbe, mediated the radioprotective effect. We further demonstrated that propionic acid bound to G-protein coupled receptor 43 (GRP43) on the surface of intestinal epithelia and increased histone acetylation and hence enhanced the expression of tight junction proteins occludin and ZO-1 and elevated the level of mucins, leading to enhanced integrity of intestinal epithelial barrier and reduced radiation-induced intestinal damage. Metformin, a first-line agent for the treatment of type II diabetes, promoted intestinal epithelial barrier integrity and reduced radiation intestinal damage through increasing the abundance of A. muciniphila. Together, our results demonstrated that A. muciniphila plays a critical role in the reduction of abdominal IR-induced intestinal damage. Application of probiotics or their regulators, such as metformin, could be an effective treatment for the protection of radiation exposure-damaged intestine.

Development and management of gastrointestinal symptoms in long-term COVID-19.

Background: Emerging evidence reveals that SARS-CoV-2 possesses the capability to disrupt the gastrointestinal (GI) homeostasis, resulting in the long-term symptoms such as loss of appetite, diarrhea, gastroesophageal reflux, and nausea. In the current review, we summarized recent reports regarding the long-term effects of COVID-19 (long COVID) on the gastrointestine. Objective: To provide a narrative review of abundant clinical evidence regarding the development and management of long-term GI symptoms in COVID-19 patients. Results: Long-term persistent digestive symptoms are exhibited in a majority of long-COVID patients. SARS-CoV-2 infection of intestinal epithelial cells, cytokine storm, gut dysbiosis, therapeutic drugs, psychological factors and exacerbation of primary underlying diseases lead to long-term GI symptoms in COVID-19 patients. Interventions like probiotics, prebiotics, fecal microbiota transplantation, and antibiotics are proved to be beneficial in preserving intestinal microecological homeostasis and alleviating GI symptoms. Conclusion: Timely diagnosis and treatment of GI symptoms in long-COVID patients hold great significance as they may contribute to the mitigation of severe conditions and ultimately lead to the improvement of outcomes of the patients.

Exploration of the shared genetic biomarkers in Alzheimer's disease and chronic kidney disease using integrated bioinformatics analysis.

In order to investigate the potential link between Alzheimer's disease (AD) and chronic kidney disease (CKD), we conducted a comprehensive analysis using a bioinformatics approach. We downloaded AD and CKD datasets from the Gene Expression Omnibus database and analyzed differentially expressed genes and weighted gene co-expression networks to identify candidate genes for AD and CKD. We used a combination of the least absolute shrinkage and selection operator and random forest algorithms to select the shared genes. Subsequently, we shared genes and performed an immune infiltration analysis to investigate the association between different immune cell types and shared genes. Finally, we elucidated the relationship between the expression levels of the shared genes in disease samples and cells using single-cell analysis. Our analysis identified 150 candidate genes that may be primarily involved in immune inflammatory responses and energy metabolism pathways. We found that JunD Proto-Oncogene, ALF transcription elongation factor 1, and ZFP36 Ring Finger Protein Like 1 were the best co-diagnostic markers for AD and CKD based on the results of Least Absolute Shrinkage Selection Operator analysis and the random forest algorithm. Based on the results of immune infiltration analysis, macrophages and T-cells play a significant role in the progression of AD and CKD. Our scRNA-sequencing data showed that the 3 shared genes in AD were significantly expressed in astrocytes, excitatory neurons, oligodendrocytes, and MAIT cells. The 3 shared genes in CKD were significantly expressed in oligodendrocytes, neutrophils, fibroblasts, astrocytes, and T-cells. JunD Proto-Oncogene, ALF transcription elongation factor 1, and ZFP36 Ring Finger Protein Like 1 genes are the best diagnostic markers for AD and CKD.

Tracking tumor alteration in glioma through serum fibroblast activation protein combined with image.

PURPOSE: Detecting tumor progression of glioma continues to pose a formidable challenge. The role of fibroblast activation protein (FAP) in gliomas has been demonstrated to facilitate tumor progression. Glioma-circulating biomarkers have not yet been used in clinical practice. This study seeks to evaluate the feasibility of glioma detection through the utilization of a serum FAP marker. METHODS: We adopted enzyme-linked immunosorbent assay (ELISA) technique to quantify the relative FAP level of serum autoantibodies in a cohort of 87 gliomas. The correlation between preoperative serum autoantibody relative FAP levels and postoperative pathology, including molecular pathology was investigated. A series of FAP tests were conducted on 33 cases of malignant gliomas in order to ascertain their efficacy in monitoring the progression of the disease in relation to imaging observations. To validate the presence of FAP expression in tumors, immunohistochemistry was conducted on four gliomas employing a FAP-specific antibody. Additionally, the investigation encompassed the correlation between postoperative tumor burden, as assessed through volumetric analysis, and the relative FAP level of serum autoantibodies. RESULTS: A considerable proportion of gliomas exhibited a significantly increased level of serum autoantibody relative FAP level. This elevation was closely associated with both histopathology and molecular pathology, and demonstrated longitudinal fluctuations and variations corresponding to the progression of the disease The correlation between the rise in serum autoantibody relative FAP level and tumor progression and/or exacerbation of symptoms was observed. CONCLUSIONS: The measurement of serum autoantibody relative FAP level can be used to detect the disease as a valuable biomarker. The combined utilization of its detection alongside MR imaging has the potential to facilitate a more accurate and prompt diagnosis.

4D-DIA quantitative proteomics revealed the core mechanism of diabetic retinopathy after berberine treatment.

OBJECTIVE: To reveal the core mechanism of berberine (BBR) in the treatment of diabetic retinopathy (DR), by using Four-dimensional independent data acquisition (4D-DIA) proteomics combined bioinformatics analysis with experimental validation. METHODS: DR injury model was established by injecting streptozotocin intraperitoneally. At 8 weeks after BBR administration, optical coherence tomography (OTC) photos and Hematoxylin-eosin staining from retina in each group were performed, then the retina was collected for 4D-DIA quantitative proteomics detection. Moreover, difference protein analysis, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, protein-protein interaction (PPI) network, as well as molecular docking was performed, respectively. In the part of experiment, Western blot (WB) and immunofluorescent staining was used to confirm the change and distribution of carbonic anhydrase 1 (CA1), one of the most important molecules from quantitative PCR detection. Lastly, RNA knockdown was used to determine the crucial role of CA1 in retinal pigment epithelial cells (RPEs) administrated with berberine. RESULTS: OCT detection showed that the outer nucleus, inner layer and outer accessory layer of RPEs were thinned in DR group, compared with in sham one, while they were thickened after berberine administration, when compared with in DR group. 10 proteins were screened out by using proteomic analysis and Venny cross plot, in which, denn domain containing 1A (DENND1A) and UTP6 small subunit processome component (UTP6) was down-regulated, while ATPase copper transporting alpha (ATP7A), periplakin (PPL), osteoglycin (OGN), nse1 Homolog (NSMCE1), membrane metalloendopeptidase (MME), lim domain only 4 (LMO4), CA1 and fibronectin 1 (FN1) was up-regulated in DR group, and the BBR treatment can effectively reverse their expressions. PPI results showed that 10 proteins shared interactions with each other, but only ATP7A, FN1 and OGN exhibited directly associated with each other. Moreover, we enlarged the linked relation up to 15 genes in network, based on 10 proteins found from proteomics detection, so as to perform deep GO and KEGG analysis. As a result, the most important biological process is involving rRNA processing; the most important cell component is small subunit processor; the most important molecular function is Phospholipid binding; the KEGG pathway was Ribosome biogenesis in eukaryotes. Moreover, molecular docking showed that LMO4, ATP7A, PPL, NSMCE1, MME, CA1 could form a stable molecular binding pattern with BBR. Of these, the mRNA expression of CA1, PPL and ATP7A and the protein level of CA1 was increased in DR, and decreased in BBR group. Lastly, CA1 RNA knockdown confirmed the crucial role of CA1 in RPE administered with BBR. CONCLUSION: The present findings confirmed the role of BBR in DR treatment and explained associated molecular network mechanism, in which, CA1 could be considered as a crucial candidate in the protection of RPEs with berberine treatment.

Pulse pressure and its association with body composition among Chinese men and women without diagnosed hypertension: the China Kadoorie Biobank.

BACKGROUND: Wide brachial pulse pressure (PP) has been associated with cardiovascular events, while its population distribution and association with body composition were poorly characterized in large populations. METHODS: We evaluated the age and sex distributions of PP and its associations with body composition using baseline data from the China Kadoorie Biobank. A total of 434 200 participants without diagnosed hypertension were included in the analysis. Wide PP was defined as PP above 65 mmHg. Body composition variables, including BMI, waist circumference, waist-to-hip ratio (WHR), fat mass index (FMI), fat-free mass index (FFMI), and body fat percentage (BF%), were obtained from bioelectrical impedance analysis. RESULTS: Overall, 14.3% of the participants had wide PP. Older age was consistently associated with wider PP in women but only after the andropause stage in men. The independent associations of BMI with wide PP were stronger than other body composition measures. The adjusted differences (men/women, mmHg) in PP per standard deviation (SD) increase in BMI (1.55/1.47) were higher than other body composition (BF%: 0.32/0.64, waist circumference: 0.33/0.39; WHR: 0.49/0.42). In addition, sex differences were observed. In men, the per SD difference in PP was higher for FFMI than for FMI (0.91 vs. 0.67, P  < 0.05), whereas in women, it was higher for FMI than for FFMI (1.01 vs. 0.72, P  < 0.05). CONCLUSION: Our nationwide population-based study presented the sex-specific distribution of PP over age and identified differential associations of PP with fat and fat-free mass in men and women.

Differential Gut Microbiota, Dietary Intakes in Constipation Patients with or without Hypertension.

SCOPE: Diet and gut microbiota are involved in blood pressure regulations, but few studies have focused on the constipation patients. The study seeks to identify differences in gut microbiota between hypertensive and normotensive subjects in constipation patients, analyzes the relationship between dietary patterns and blood pressure, and explores mediation effects of gut microbiota. METHODS AND RESULTS: Gut microbial genera and dietary information of 186 functional constipation participants are characterized by 16S rRNA sequencing and a food frequency questionnaire. The hypertensive subjects shows lower α-diversity and ß-diversity of gut microbiota than normotensive (p < 0.05) and 17 differential microbial genera. The dried-beans intake frequency inversely correlated with systolic and diastolic blood pressure after multivariate adjustment (r = -0.273, p-FDR < 0.01; r = -0.251, p-FDR = 0.026, respectively). Logistic regression indicates that the individuals often consumed dried-beans have a lower hypertension risk than those never consumed [OR = 0.137, 95% CI: (0.022, 0.689), p = 0.022]. A marginal mediating effect of the genus Monoglobus is observed for the association between high-fiber dietary pattern and hypertension. CONCLUSION: In patients with functional constipation, hypertension-related gut microbial differences are identified. Dried-beans intake is inversely associated with blood pressure, and a genus may potentially mediate the association between high-fiber dietary pattern and hypertension.