Phospho-eIF4E stimulation regulates coronavirus entry by selective expression of cell membrane-residential factors.

The eukaryotic translation initiation factor eIF4E can regulate cellular translation via phosphorylation on serine 209. In a recent study, by two rounds of TMT relative quantitative proteomics, we found that phosphorylated eIF4E (p-eIF4E) favors the translation of selected mRNAs, and the encoded proteins are mainly involved in ECM-receptor, focal adhesion, and PI3K-Akt signaling. The current paper is focused on the relationship between p-eIF4E and the downstream host cell proteins, and their presumed effect on efficient entry of PEDV. We found that the depletion of membrane-residential factor TSPAN3, CD63, and ITGB2 significantly inhibited viral invasion of PEDV, and reduced the entry of pseudotyped particles PEDV-pp, SARS-CoV-pp, and SARS-CoV-2-pp. The specific antibodies of TSPAN3, CD63, and ITGB2 blocked the adsorption of PEDV into host cells. Moreover, we detected that eIF4E phosphorylation was increased at 1 h after PEDV infection, in accordance with the expression of TSPAN3, CD63, and ITGB2. Similar trends appeared in the intestines of piglets in the early stage of PEDV challenge. Compared with Vero cells, S209A-Vero cells in which eIF4E cannot be phosphorylated showed a decrease of invading PEDV virions. MNK kinase inhibitor blocked PEDV invasion, as well as reduced the accumulation of TSPAN3, CD63, and ITGB2. Further study showed that the ERK-MNK pathway was responsible for the regulation of PEDV-induced early phosphorylation of eIF4E. This paper demonstrates for the first time the connections among p-eIF4E stimulation and membrane-residential host factors. Our findings also enrich the understanding of the biological function of phosphorylated eIF4E during the viral life cycle.IMPORTANCEThe eukaryotic translation initiation factor eIF4E can regulate cellular translation via phosphorylation. In our previous study, several host factors susceptible to a high level of p-eIF4E were found to be conducive to viral infection by coronavirus PEDV. The current paper is focused on cell membrane-residential factors, which are involved in signal pathways that are sensitive to phosphorylated eIF4E. We found that the ERK-MNK pathway was activated, which resulted in the stimulation of phosphorylation of eIF4E in early PEDV infection. Phospho-eIF4E promoted the viral invasion of PEDV by upregulating the expression of host factors TSPAN3, CD63, and ITGB2 at the translation level rather than at the transcription level. Moreover, TSPAN3, CD63, or ITGB2 facilitates the efficient entry of coronavirus SARS-CoV, SARS-CoV-2, and HCoV-OC43. Our findings broaden our insights into the dynamic phosphorylation of eIF4E during the viral life cycle, and provide further evidence that phosphorylated eIF4E regulates selective translation of host mRNA.

UPK3A+ umbrella cell damage mediated by TLR3-NR2F6 triggers programmed destruction of urothelium in Hunner-type interstitial cystitis/painful bladder syndrome.

Urothelial damage and barrier dysfunction emerge as the foremost mechanisms in Hunner-type interstitial cystitis/bladder pain syndrome (HIC). Although treatments aimed at urothelial regeneration and repair have been employed, their therapeutic effectiveness remains limited due to the inadequate understanding of specific cell types involved in damage and the lack of specific molecular targets within these mechanisms. Therefore, we harnessed single-cell RNA sequencing to elucidate the heterogeneity and developmental trajectory of urothelial cells within HIC bladders. Through reclustering, we identified eight distinct clusters of urothelial cells. There was a significant reduction in UPK3A+ umbrella cells and a simultaneous increase in progenitor-like pluripotent cells (PPCs) within the HIC bladder. Pseudotime analysis of the urothelial cells in the HIC bladder revealed that cells faced challenges in differentiating into UPK3A+ umbrella cells, while PPCs exhibited substantial proliferation to compensate for the loss of UPK3A+ umbrella cells. The urothelium in HIC remains unrepaired, despite the substantial proliferation of PPCs. Thus, we propose that inhibiting the pivotal signaling pathways responsible for the injury to UPK3A+ umbrella cells is paramount for restoring the urothelial barrier and alleviating lower urinary tract symptoms in HIC patients. Subsequently, we identified key molecular pathways (TLR3 and NR2F6) associated with the injury of UPK3A+ umbrella cells in HIC urothelium. Finally, we conducted in vitro and in vivo experiments to confirm the potential of the TLR3-NR2F6 axis as a promising therapeutic target for HIC. These findings hold the potential to inhibit urothelial injury, providing promising clues for early diagnosis and functional bladder self-repair strategies for HIC patients. © 2024 The Pathological Society of Great Britain and Ireland.

ZFYVE19 deficiency: a ciliopathy involving failure of cell division, with cell death.

BACKGROUND AND AIMS: Variants in ZFYVE19 underlie a disorder characterised by progressive portal fibrosis, portal hypertension and eventual liver decompensation. We aim to create an animal model to elucidate the pathogenic mechanism. METHODS: Zfyve19 knockout (Zfyve19-/- ) mice were generated and exposed to different liver toxins. Their livers were characterised at the tissue, cellular and molecular levels. Findings were compared with those in wild-type mice and in ZFYVE19-deficient patients. ZFYVE19 knockout and knockdown retinal pigment epithelial-1 cells and mouse embryonic fibroblasts were generated to study cell division and cell death. RESULTS: The Zfyve19-/- mice were normal overall, particularly with respect to hepatobiliary features. However, when challenged with α-naphthyl isothiocyanate, Zfyve19-/- mice developed changes resembling those in ZFYVE19-deficient patients, including elevated serum liver injury markers, increased numbers of bile duct profiles with abnormal cholangiocyte polarity and biliary fibrosis. Failure of cell division, centriole and cilia abnormalities, and increased cell death were observed in knockdown/knockout cells. Increased cell death and altered mRNA expression of cell death-related signalling pathways was demonstrated in livers from Zfyve19-/- mice and patients. Transforming growth factor-ß (TGF-ß) and Janus kinase-Signal Transducer and Activator of Transcription 3 (JAK-STAT3) signalling pathways were upregulated in vivo, as were chemokines such as C-X-C motif ligands 1, 10 and 12. CONCLUSIONS: Our findings demonstrated that ZFYVE19 deficiency is a ciliopathy with novel histological features. Failure of cell division with ciliary abnormalities and cell death activates macrophages and may thus lead to biliary fibrosis via TGF-ß pathway in the disease.

Immunotherapy and the ovarian cancer microenvironment: Exploring potential strategies for enhanced treatment efficacy.

Despite progress in cancer immunotherapy, ovarian cancer (OC) prognosis continues to be disappointing. Recent studies have shed light on how not just tumour cells, but also the complex tumour microenvironment, contribute to this unfavourable outcome of OC immunotherapy. The complexities of the immune microenvironment categorize OC as a 'cold tumour'. Nonetheless, understanding the precise mechanisms through which the microenvironment influences the effectiveness of OC immunotherapy remains an ongoing scientific endeavour. This review primarily aims to dissect the inherent characteristics and behaviours of diverse cells within the immune microenvironment, along with an exploration into its reprogramming and metabolic changes. It is expected that these insights will elucidate the operational dynamics of the immune microenvironment in OC and lay a theoretical groundwork for improving the efficacy of immunotherapy in OC management.

Five-Year Clinical Trial of the Low-Concentration Atropine for Myopia Progression (LAMP) Study: Phase 4 Report.

PURPOSE: To evaluate (1) the long-term efficacy of low-concentration atropine over 5 years, (2) the proportion of children requiring re-treatment and associated factors, and (3) the efficacy of pro re nata (PRN) re-treatment using 0.05% atropine from years 3 to 5. DESIGN: Randomized, double-masked extended trial. PARTICIPANTS: Children 4 to 12 years of age originally from the Low-Concentration Atropine for Myopia Progression (LAMP) study. METHODS: Children 4 to 12 years of age originally from the LAMP study were followed up for 5 years. During the third year, children in each group originally receiving 0.05%, 0.025%, and 0.01% atropine were randomized to continued treatment and treatment cessation. During years 4 and 5, all continued treatment subgroups were switched to 0.05% atropine for continued treatment, whereas all treatment cessation subgroups followed a PRN re-treatment protocol to resume 0.05% atropine for children with myopic progressions of 0.5 diopter (D) or more over 1 year. Generalized estimating equations were used to compare the changes in spherical equivalent (SE) progression and axial length (AL) elongation among groups. MAIN OUTCOMES MEASURES: (1) Changes in SE and AL in different groups over 5 years, (2) the proportion of children who needed re-treatment, and (3) changes in SE and AL in the continued treatment and PRN re-treatment groups from years 3 to 5. RESULTS: Two hundred seventy (82.8%) of 326 children (82.5%) from the third year completed 5 years of follow-up. Over 5 years, the cumulative mean SE progressions were -1.34 ± 1.40 D, -1.97 ± 1.03 D, and -2.34 ± 1.71 D for the continued treatment groups with initial 0.05%, 0.025%, and 0.01% atropine, respectively (P = 0.02). Similar trends were observed in AL elongation (P = 0.01). Among the PRN re-treatment group, 87.9% of children (94/107) needed re-treatment. The proportion of re-treatment across all studied concentrations was similar (P = 0.76). The SE progressions for continued treatment and PRN re-treatment groups from years 3 to 5 were -0.97 ± 0.82 D and -1.00 ± 0.74 D (P = 0.55) and the AL elongations were 0.51 ± 0.34 mm and 0.49 ± 0.32 mm (P = 0.84), respectively. CONCLUSIONS: Over 5 years, the continued 0.05% atropine treatment demonstrated good efficacy for myopia control. Most children needed to restart treatment after atropine cessation at year 3. Restarted treatment with 0.05% atropine achieved similar efficacy as continued treatment. Children should be considered for re-treatment if myopia progresses after treatment cessation. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

A Green Environmental Protection Photocatalytic Molecular Reactor for Aerobic Oxidation of Sulfide to Sulfoxide.

The design and synthesis of metal-organic frameworks (MOFs) as photocatalytic molecular reactors for varied reactions have drawn great attention. In this work, we designed a novel photoactive perylenediimides-based (PDI) carboxylate ligand N,N'-di(3',3",5',5"-tetrakis(4-carboxyphenyl))-1,2,6,7-tetrachloroperylene-3,4,9,10-tetracarboxylic acid diimide (Cl-PDI-TA) and use it to successfully synthesize a novel Zr(IV)-based MOF 1 constructed from [Zr6 O8 (H2 O)8 ]8+ clusters bridged by Cl-PDI-TA ligands. Structural analysis revealed that Zr-MOF 1 manifests a 3D framework with (4,8)-connected csq topology and possesses triangular channels of ~17 Šand mesoporous hexagonal channels of ~26 Šalong c-axis. Moreover, the synthesized Zr-MOF 1 exhibits visible-light absorption and efficient photoinduced free radical generation property, making it a promising photocatalytic molecular reactor. When Zr-MOF 1 was used as a photocatalyst for the aerobic oxidation of sulfides under irradiation of visible light, it could afford the corresponding sulfoxides with high yield and selectivity. Experimental results demonstrated that the substrate sulfides could be fixed in the pores of 1 and directly transformed to the products sulfoxides in the solid state. Furthermore, the mechanism for the photocatalytic transformation was also investigated and the results revealed that the singlet oxygen (1 O2 ) and superoxide radical (O2 ⋅- ) generated by the energy transfer and electron transfer from the photoexcited Zr-MOF to oxidants were the main active species for the catalytic reactions. This work offers a perceptive comprehension of the mechanism in PDI-based MOFs for further study on photocatalytic reactions.

Integrated analysis of transcriptome and metabolome reveals the regulatory mechanism of largemouth bass (Micropterus salmoides) in response to Nocardia seriolae infection.

Nocardia seriolae is a severe bacterial pathogen that has seriously affected the development of aquaculture industry. Largemouth bass (Micropterus salmoides) is a commercially significant freshwater fish that suffers a variety of environmental threats, including bacterial pathogens. However, the immune responses and metabolic alterations of largemouth bass to N. seriolae infection remain largely unclear. We discovered that N. seriolae caused pathological alterations in largemouth bass and shifted the transcript of immune-related and apoptotic genes in head kidney after infection. To answer the aforementioned question, a combined transcriptome and metabolome analysis was employed to explore the alterations in genes, metabolites, and metabolic pathways in largemouth bass following bacterial infection. A total of 3579 genes and 1929 metabolites are significant differentially changed in the head kidney post infection. In response to N. seriolae infection, host modifies the PI3K-Akt signaling pathway, TCA cycle, glycolysis, and amino acid metabolism. The integrated analysis of transcriptome and metabolome suggested that with the arginine metabolism pathway as the core, multiple biomarkers (arg gene, arginine) are involved in the antibacterial and immune functions of largemouth bass. Thus, we hypothesized that arginine plays a crucial role in the immune responses of largemouth bass against N. seriolae infection, and increasing arginine levels suitably is beneficial for the host against bacterial infection. Our results shed light on the regulatory mechanism of largemouth bass resistance to N. seriolae infection and contributed to the development of more effective N. seriolae resistance strategies.

Effects of antimicrobial peptides from dietary Hermetia illucens larvae on the growth, immunity, gene expression, intestinal microbiota and resistance to Aeromonas hydrophila of juvenile red claw crayfish (Cherax quadricarinatus).

Antimicrobial peptides (AMPs), which are widely present in animals and plants, have a broad distribution, strong broad-spectrum antibacterial activity, low likelihood of developing drug resistance, high thermal stability and antiviral properties. The present study investigated the effects of adding AMPs from Hermetia illucens larvae on the growth performance, muscle composition, antioxidant capacity, immune response, gene expression, antibacterial ability and intestinal microbiota of Cherax quadricarinatus (red claw crayfish). Five experimental diets were prepared by adding 50 (M1), 100 (M2), 150 (M3) and 200 (M4) mg/kg of crude AMP extract from H. illucens larvae to the basal diet feed, which was also used as the control (M0). After an eight-week feeding experiment, it was discovered that the addition of 100-150 mg/kg of H. illucens larvae AMPs to the feed significantly improved the weight gain rate and specific growth rate of C. quadricarinatus. Furthermore, the addition of H. illucens larvae AMPs to the feed had no significant effect on the moisture content, crude protein, crude fat and ash content of the C. quadricarinatus muscle. The addition of 100-150 mg/kg of H. illucens larvae AMPs in the feed also increased the antioxidant capacity, nonspecific immune enzyme activity and related gene expression levels in C. quadricarinatus, thereby enhancing their antioxidant capacity and immune function. The H. illucens larvae AMPs improved the structure and composition of the intestinal microbiota of C. quadricarinatus, increasing the microbial community diversity of the crayfish gut. Finally, the addition of 100-150 mg/kg of H. illucens larvae AMPs in the feed enhanced the resistance of C. quadricarinatus against Aeromonas hydrophila, improving the survival rate of the crayfish. Based on the aforementioned findings, it is recommended that H. illucens larvae AMPs be incorporated into the C. quadricarinatus feed at a concentration of 100-150 mg/kg.

Effects of dietary chitosan oligosaccharide on the growth, intestinal microbiota and immunity of juvenile red claw crayfish (Cherax quadricarinatus).

This study aimed to evaluate the potential benefits of chitosan oligosaccharide (COS) on red claw crayfish (Cherax quadricarinatus) and explore its underlying mechanisms. The crayfish were randomly divided into six groups, and the diets were supplemented with COS at levels of 0 (C0), 0.2 (C1), 0.4 (C2), 0.6 (C3), 0.8 (C4), and 1 (C5) g kg-1. Treatment with COS significantly improved the growth performance of the crayfish with a higher weight gain rate (WGR) and specific growth rate (SGR) in the C2 group compared to the C0 group. Additionally, the content of crude protein in the crayfish muscles in the C1 group was significantly higher than that of the C0 group. Regarding non-specific immunity, the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and alkaline phosphatase (AKP), and the levels of expression of the genes related to immunity (SOD; anti-lipopolysaccharide factor [ALF]; thioredoxin1 [Trx1]; C-type lysozyme, [C-LZM]; and GSH-Px) in the hepatopancreas and hemolymph increased significantly (P < 0.05) after supplementation with 0.4 g kg-1 of COS, while the content of malondialdehyde (MDA) decreased (P < 0.05). The survival rate of C. quadricarinatus increased (P < 0.05) in the C2, C3, C4, and C5 groups after the challenge with Aeromonas hydrophila. This study found that COS has the potential to modulate the composition of the intestinal microbiota and significantly reduce the abundance of species of the phylum Proteobacteria and the genera Aeromonas and Vibrio in the gut of C. quadricarinatus, while the abundance of bacteria in the phylum Firmicutes and the genus Candidatus_Hepatoplasma improved significantly. This study suggests that the inclusion of COS in the diet of C. quadricarinatus can enhance growth, boost immunity, and increase resistance to infection with A. hydrophila, especially when supplemented at 0.4-0.8 g kg-1.

Effects of dietary astaxanthin on growth performance, muscle composition, non-specific immunity, gene expression, and ammonia resistance of juvenile ivory shell (Babylonia areolate).

Astaxanthin is one of the important immunopotentators in aquaculture. However, little is known about the physiological changes and stress resistance effects of astaxanthin in marine gastropods. In this study, the effects of different astaxanthin concentrations (0, 25, 50, 75, and 100 mg/kg) on the growth, muscle composition, immune function, and resistance to ammonia stress in Babylonia areolata were investigated after three months of rearing. With the increase in astaxanthin content, the weight gain rate (WGR), specific growth rate (SGR), and survival rate (SR) of B. areolata showed an increasing trend. The 75-100 mg/kg group was significantly higher than the control group (0 mg/kg). There was no significant difference in the flesh shell ratio (FSR), viscerosomatic index (VSI), and soft tissue index (STI) of the experimental groups. Astaxanthin (75 mg/kg) significantly increased muscle crude protein content and increased hepatopancreas alkaline phosphatase (AKP), superoxide dismutase (SOD), and catalase (CAT) activity. Astaxanthin (75-100 mg/kg) significantly increased the total antioxidant capacity (T-AOC) and acid phosphatase (ACP) of the hepatopancreas and decreased the malondialdehyde (MDA) content of B. areolata. Astaxanthin significantly induced the expression levels of functional genes, such as SOD, Cu/ZnSOD, ferritin, ACP, and CYC in hepatopancreas and increased the survival rate of B. areolata under ammonia stress. The addition of 75-100 mg/kg astaxanthin to the feed improved the growth performance, muscle composition, immune function, and resistance to ammonia stress of B. areolata.

Clinical implications and mechanism of CST1 in gastric carcinoma based on database screening.

Gastric cancer (GC) remains one of the most common malignant tumours worldwide, with extremely high morbidity and mortality rates. An in-depth understanding of the pathogenesis of GC is key to the future diagnosis and treatment of GC. In this study, we analysed the differentially expressed genes (DEGs) in gastric carcinoma (GC) through GEO database and their clinical implications, with the aim of providing clinical reference and guidance. We selected the GSE118916 dataset for bioinformatics analysis and identified a total of 3231 DEGs. Keywords, including extracellular region, vesicle, protein digestion and absorption, ECM-receptor interaction, etc., of DEGs can be seen by the GO and KEGG enrichment analysis. The online database determined up-regulated CST1 in GC and some other tumors, as well as a close connection between CST1 with patient prognosis. Subsequently, we collected a number of GC clinical cases and examined the expression of CST1, which was seen to be highly expressed in GC, with a favorable diagnostic effect on the occurrence of GC (P<0.05) and a strong correlation with TNM stage, tumor invasion, tumor diameter and differentiation (P<0.05). In other words, CST1 is closely related to the occurrence and development of GC, and has the potential to be a breakthrough in the diagnosis and treatment of GC in the future.

Enhancement of microbial community dynamics and metabolism in compost through ammonifying cultures inoculation.

The efficient use of livestock and poultry manure waste has become a global challenge, with microorganisms playing an important role. To investigate the impact of novel ammonifying microorganism cultures (NAMC) on microbial community dynamics and carbon and nitrogen metabolism, five treatments [5% (v/w) sterilized distilled water, Amm-1, Amm-2, Amm-3, and Amm-4] were applied to cow manure compost. Inoculation with NAMC improved the structure of bacterial and fungal communities, enriched the populations of the functional microorganisms, enhanced the role of specific microorganisms, and promoted the formation of tight modularity within the microbial network. Further functional predictions indicated a significant increase in both carbon metabolism (CMB) and nitrogen metabolism (NMB). During the thermophilic phase, inoculated NAMC treatments boosted carbon metabolism annotation by 10.55%-33.87% and nitrogen metabolism annotation by 26.69%-63.11. Structural equation modeling supported the NAMC-mediated enhancement of NMB and CMB. In conclusion, NAMC inoculation, particularly with Amm-4, enhanced the synergistic interaction between bacteria and fungi. This collaboration promoted enzymatic catabolic and synthetic processes, resultng in positive feedback loops with the endogenous microbial community. Understanding these mechanisms not only unravels how ammonifying microorganisms influence microbial communities but also paves the way for the development of the composting industry and global waste management practices.

Associations of per- and polyfluoroalkyl substances (PFAS) and their mixture with risk of rheumatoid arthritis in the U.S. adult population.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are known environmental contaminants with immunosuppressive properties. Their connection to rheumatoid arthritis (RA), a condition influenced by the immune system, is not well studied. This research explores the association between PFAS exposure and RA prevalence. METHODS: This research utilized data from the NHANES, encompassing a sample of 10,496 adults from the 2003-2018 cycles, focusing on serum levels of several PFAS. The presence of RA was determined based on self-reports. This study used multivariable logistic regression to assess the relationship between individual PFAS and RA risk, adjusting for covariates to calculate odds ratios (ORs). The combined effects of PFAS mixtures were evaluated using BKMR, WQS regression, and quantile g-computation. Additionally, sex-specific associations were explored through stratified analysis. RESULTS: Higher serum PFOA (OR = 0.88, 95% CI: 0.79, 0.98), PFHxS (OR = 0.91, 95% CI: 0.83, 1.00), PFNA (OR = 0.87, 95% CI: 0.77, 0.98), and PFDA (OR = 0.89, 95% CI: 0.81, 0.99) concentration was related to lower odds of RA. Sex-specific analysis in single chemical models indicated the significant inverse associations were only evident in females. BKMR did not show an obvious pattern of RA estimates across PFAS mixture. The outcomes of sex-stratified quantile g-computation demonstrated that an increase in PFAS mixture was associated with a decreased odds of RA in females (OR: 0.76, 95% CI: 0.62, 0.92). We identified a significant interaction term of the WQS*sex in the 100 repeated hold out WQS analysis. Notably, a higher concentration of the PFAS mixture was significantly associated with reduced odds of RA in females (mean OR = 0.93, 95% CI: 0.88, 0.98). CONCLUSIONS: This study indicates potential sex-specific associations of exposure to various individual PFAS and their mixtures with RA. Notably, the observed inverse relationships were statistically significant in females but not in males. These findings contribute to the growing body of evidence indicating that PFAS may have immunosuppressive effects.

Effects of firsthand tobacco smoking on retinal vessel caliber: a systematic review and meta-analysis.

PURPOSE: To review the effects of firsthand tobacco smoking on central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) of firsthand tobacco smokers. METHODS: We performed a search on EMBASE and PubMed for studies up to 15th July 2022. Two independent reviewers selected studies with baseline data of CRAE and CRVE of current smokers, nonsmokers, and former smokers. Initial search identified 893 studies, of which 10 were included in the meta-analysis. Two independent reviewers extracted data from the included studies. The quality of studies was assessed by the Newcastle-Ottawa Scale. RESULTS: In this meta-analysis, 7431 nonsmokers, 2448 current smokers and 5786 former smokers, as well as 7404 nonsmokers, 2430 current smokers and 5763 former smokers were included in CRAE and CRVE analysis respectively. Nonsmokers had narrower CRVE (Weighted mean difference [WMD], -12.15; 95% CI, -17.33 - -6.96) and CRAE (WMD, -4.77; 95% CI, -7.96 - -1.57) than current smokers, and narrower CRVE (WMD, -3.08; 95% CI, -6.06 - -0.11) than former smokers. Current smokers had wider CRVE (WMD, 10.42; 95% CI, 7.80 - 13.04) and CRAE (WMD, 7.05; 95% CI, 6.65 - 7.46) than former smokers. Subgroup analysis and sensitivity analysis were performed. CONCLUSION: Firsthand tobacco smoking resulted in wider CRAE and CRVE in current and former smokers, particularly in CRVE, and such changes may not be reversible after smoking cessation. Therefore, retinal vessel caliber may reflect the effects of firsthand tobacco smoking and be used to estimate the risk of cardiovascular diseases.

Anterior chamber and angle characteristics in Chinese children (6-11 years old) with different refractive status using swept-source optical coherence tomography.

BACKGROUND: The anatomic structure of the anterior chamber (AC) helps to explain differences in refractive status in school-aged children and is closely associated with primary angle closure (PAC). The aim of this study was to quantify and analyze the anterior chamber and angle (ACA) characteristics in Chinese children with different refractive status by swept-source optical coherence tomography (SS-OCT). METHODS: In a cross-sectional observational study, 383 children from two primary schools in Shandong Province, China, underwent a complete ophthalmic examination. First, the anterior chamber depth (ACD), anterior chamber width (ACW), angle-opening distance (AOD), and trabecular-iris space area (TISA) were evaluated automatically using a CASIA2 imaging device. AOD and TISA were measured at 500, 750 µm nasal (N1 and N2, respectively), and temporal (T1 and T2, respectively) to the scleral spur (SS). Cycloplegic refraction and axial length (AL) were then measured. According to spherical equivalent refraction (SER), the children were assigned to hyperopic (SER > 0.50D), emmetropic (-0.50D < SER ≤ 0.50D), and myopic groups (SER ≤ -0.50D). RESULTS: Out of the 383 children, 349 healthy children (160 girls) with a mean age of 8.23 ± 1.06 years (range: 6-11 years) were included. The mean SER and AL were - 0.10 ± 1.57D and 23.44 ± 0.95 mm, respectively. The mean ACD and ACW were 3.17 ± 0.24 mm and 11.69 ± 0.43 mm. The mean AOD were 0.72 ± 0.25, 0.63 ± 0.22 mm at N1, T1, and 0.98 ± 0.30, 0.84 ± 0.27 mm at N2, T2. The mean TISA were 0.24 ± 0.09, 0.22 ± 0.09mm2 at N1, T1, and 0.46 ± 0.16, 0.40 ± 0.14mm2 at N2, T2. The myopic group had the deepest AC and the widest angle. Compared with boys, girls had shorter AL, shallower ACD, narrower ACW, and ACA (all p < 0.05). By Pearson's correlation analysis, SER was negatively associated with ACD, AOD, and TISA. AL was positively associated with ACD, ACW, AOD, and TISA. In the multiple regression analysis, AOD and TISA were associated with deeper ACD, narrower ACW, and longer AL. CONCLUSION: In primary school students, the myopic eyes have deeper AC and wider angle. ACD, ACW, AOD, and TISA all increase with axial elongation. ACA is highly correlated with deeper ACD.

Identification of potential crucial genes shared in psoriasis and ulcerative colitis by machine learning and integrated bioinformatics.

BACKGROUND: Mounting evidence suggest that there are an association between psoriasis and ulcerative colitis (UC), although the common pathogeneses are not fully understood. Our study aimed to find potential crucial genes in psoriasis and UC through machine learning and integrated bioinformatics. METHODS: The overlapping differentially expressed genes (DEGs) of the datasets GSE13355 and GSE87466 were identified. Then the functional enrichment analysis was performed. The overlapping genes in LASSO, SVM-RFE and key module in WGCNA were considered as potential crucial genes. The receiver operator characteristic (ROC) curve was used to estimate their diagnostic confidence. The CIBERSORT was conducted to evaluate immune cell infiltration. Finally, the datasets GSE30999 and GSE107499 were retrieved to validate. RESULTS: 112 overlapping DEGs were identified in psoriasis and UC and the functional enrichment analysis revealed they were closely related to the inflammatory and immune response. Eight genes, including S100A9, PI3, KYNU, WNT5A, SERPINB3, CHI3L2, ARNTL2, and SLAMF7, were ultimately identified as potential crucial genes. ROC curves showed they all had high confidence in the test and validation datasets. CIBERSORT analysis indicated there was a correlation between infiltrating immune cells and potential crucial genes. CONCLUSION: In our study, we focused on the comprehensive understanding of pathogeneses in psoriasis and UC. The identification of eight potential crucial genes may contribute to not only understanding the common mechanism, but also identifying occult UC in psoriasis patients, even serving as therapeutic targets in the future.

The potential health risks of N,N-dimethylformamide: An updated review.

N,N-dimethylformamide (DMF) is a universally used industrial material with exponential growth in production and consumption worldwide. The frequently reported occupational DMF poisoning cases in some countries and the gradually recognized unavoidable health risks to the general population highlight that DMF should still be a matter of concern. Previous studies have demonstrated that the liver is the primary target organ of DMF exposure and multiple mechanisms have been revealed. However, most of these studies investigate the detrimental effects of acute and subacute DMF exposure, while the effects of chronic DMF exposure are rarely studied. Furthermore, the key mechanism for the acute hepatotoxicity of DMF remains to be elucidated. Future research may focus on the identification of efficient preventive measures against the toxicity of DMF to occupational workers, the investigation of the detrimental effects of DMF at environmentally relevant doses, and the studies on the elimination and recycling of DMF in industrial wastes. Herein, we present an updated review of the metabolism of DMF, the biomarker of DMF exposure, underlying molecular mechanisms of DMF-induced hepatotoxicity, and the toxicity of DMF to both occupational workers and general populations and discuss the possible directions in future studies.

Improving the Prognostic Evaluation Precision of Hospital Outcomes for Heart Failure Using Admission Notes and Clinical Tabular Data: Multimodal Deep Learning Model.

BACKGROUND: Clinical notes contain contextualized information beyond structured data related to patients' past and current health status. OBJECTIVE: This study aimed to design a multimodal deep learning approach to improve the evaluation precision of hospital outcomes for heart failure (HF) using admission clinical notes and easily collected tabular data. METHODS: Data for the development and validation of the multimodal model were retrospectively derived from 3 open-access US databases, including the Medical Information Mart for Intensive Care III v1.4 (MIMIC-III) and MIMIC-IV v1.0, collected from a teaching hospital from 2001 to 2019, and the eICU Collaborative Research Database v1.2, collected from 208 hospitals from 2014 to 2015. The study cohorts consisted of all patients with critical HF. The clinical notes, including chief complaint, history of present illness, physical examination, medical history, and admission medication, as well as clinical variables recorded in electronic health records, were analyzed. We developed a deep learning mortality prediction model for in-hospital patients, which underwent complete internal, prospective, and external evaluation. The Integrated Gradients and SHapley Additive exPlanations (SHAP) methods were used to analyze the importance of risk factors. RESULTS: The study included 9989 (16.4%) patients in the development set, 2497 (14.1%) patients in the internal validation set, 1896 (18.3%) in the prospective validation set, and 7432 (15%) patients in the external validation set. The area under the receiver operating characteristic curve of the models was 0.838 (95% CI 0.827-0.851), 0.849 (95% CI 0.841-0.856), and 0.767 (95% CI 0.762-0.772), for the internal, prospective, and external validation sets, respectively. The area under the receiver operating characteristic curve of the multimodal model outperformed that of the unimodal models in all test sets, and tabular data contributed to higher discrimination. The medical history and physical examination were more useful than other factors in early assessments. CONCLUSIONS: The multimodal deep learning model for combining admission notes and clinical tabular data showed promising efficacy as a potentially novel method in evaluating the risk of mortality in patients with HF, providing more accurate and timely decision support.

Cell structure damage contributes to antifungal activity of sodium propylparaben against Trichothecium roseum.

Trichothecium roseum is a type of fungus that causes pink rot in muskmelon after the melons are harvested. Pink rot leads to severe decay during storage and causes the production of toxins that can be harmful to human health. Sodium propylparaben (SPP, IUPAC name: sodium; 4-propoxycarbonylphenolate) is an antimicrobial preservative that can be used to treat the inedible parts of fruits in addition to food, medications, and packaging. In this study, the effectiveness of SPP in inhibiting T. roseum was tested, and the inhibition mechanism was investigated. The results show that SPP inhibited the growth and spore germination of T. roseum. The malondialdehyde (MDA) content, propidium iodide staining, alkaline phosphatase (AKP) activity, and calcofluor white (CFW) staining results show that SPP produced a disruption of the cell membrane and cell wall integrity of T. roseum. Scanning and transmission electron microscopy (SEM and TEM, respectively) results also indicate that SPP disrupted the cellular structure of T. roseum. Meanwhile, the large amounts of superoxide anion and hydrogen peroxide in T. roseum accumulated due to the effects of SPP on the activities of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, superoxide dismutase, and decreased catalase. In addition, SPP caused a significant reduction in the incidence rate and disease degree of muskmelon pink rot in vivo. In conclusion, SPP appears to be effective against T. roseum via disruption of the cell membrane and wall. SPP could be used to manage melon pink rot after fruit harvesting because of its disease inhibition effect in vivo.

Co-composting of dewatered sludge and wheat straw with newly isolated Xenophilus azovorans: Carbon dynamics, humification, and driving pathways.

Composting is a biological reaction caused by microorganisms. Composting efficiency can be adequately increased by adding biochar and/or by inoculating with exogenous microorganisms. In this study, we looked at four methods for dewatered sludge waste (DSW) and wheat straw (WS) aerobic co-composting: T1 (no additive), T2 (5% biochar), T3 (5% of a newly isolated strain, Xenophilus azovorans (XPA)), and T4 (5% of biochar-immobilized XPA (BCI-XPA)). Throughout the course of the 42-day composting period, we looked into the carbon dynamics, humification, microbial community succession, and modifications to the driving pathways. Compared to T1 and T2, the addition of XPA (T3) and BCI-XPA (T4) extended the thermophilic phase of composting without negatively affecting compost maturation. Notably, T4 exhibited a higher seed germination index (132.14%). Different from T1 and T2 treatments, T3 and T4 treatments increased CO2 and CH4 emissions in the composting process, in which the cumulative CO2 emissions increased by 18.61-47.16%, and T3 and T4 treatments also promoted the formation of humic acid. Moreover, T4 treatment with BCI-XPA addition showed relatively higher activities of urease, polyphenol oxidase, and laccase, as well as a higher diversity of microorganisms compared to other processes. The Functional Annotation of Prokaryotic Taxa (FAPROTAX) analysis showed that microorganisms involved in the carbon cycle dominated the entire composting process in all treatments, with chemoheterotrophy and aerobic chemoheterotrophy being the main pathways of organic materials degradation. Moreover, the presence of XPA accelerated the breakdown of organic materials by catabolism of aromatic compounds and intracellular parasite pathways. On the other hand, the xylanolysis pathway was aided in the conversion of organic materials to dissolved organics by the addition of BCI-XPA. These findings indicate that XPA and BCI-XPA have potential as additives to improve the efficiency of dewatered sludge and wheat straw co-composting.