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Abstract Asthma is a prevalent chronic disease characterized by airflow obstruction, causing breathing difficulties and wheezing. This study investigates the association between the C-reactive protein to albumin ratio (CAR) and asthma prevalence, as well as all-cause and respiratory mortality among asthma patients, using data from the 2001–2018 National Health and Nutrition Examination Survey. We included participants aged 20 years and older with complete CAR data, excluding those who were pregnant or lost to follow-up. The analysis employed weighted logistic regression and Cox proportional hazards models with stepwise adjustment, restricted cubic spline analysis for nonlinear relationships, and time-dependent ROC curves for predictive accuracy. Results showed that the highest CAR quartile significantly increased the risk of asthma (OR 1.56, 95% CI 1.38–1.78), all-cause mortality (HR 2.20, 95% CI 1.67–2.89), and respiratory mortality (HR 2.56, 95% CI 1.30–5.38). The impact of CAR on all-cause mortality was particularly significant in hypertensive patients. These findings highlight CAR’s potential as a valuable biomarker for predicting asthma prevalence and mortality, underscoring its role in asthma management and prognostication.

Objective To investigate the impact of human leukocyte antigen (HLA) functional epitope mismatch (EM) on the efficacy of platelet transfusion in patients with hematological diseases. Methods HLA genotyping was performed on platelet donors and patients with hematological diseases who applied for platelet serological cross-matching and HLA antigen matching from June 2021 to June 2023 by PCR-SBT method. HLA platelet matching was based on the principle of CREG to select donors for patients. HLA Matchmaker 4.0 software was used to analyze donor-recipient HLA EM information. The expression level and gene distribution of related HLA functional epitope (Eplet) were searched from the international HLA Epitope registry website (www.Epregistry.com.br). Retrospective analysis was conducted on clinical platelet transfusion data to evaluate the impact of HLA EM on platelet transfusion effectiveness. Results Platelet transfusion efficacy showed no correlation with gender and age, but it was associated with platelet matching strategy. When the total number of HLA EMs was less than 20, a lower total number of donor-recipient HLA EMs resulted in higher platelet transfusion efficiency (χ2=19.311, P=0.001) and higher average value of 24 h corrected count increment (CCI)(F=7.737, P

Abstract Diarrhea is characterized by alterations in the gut microbiota, metabolites, and host response to these changes. Studies have focused on the role of commensal bacteria in diarrhea; however, the effect of fungi on its pathogenesis remains unexplored. Here, using post-weaned piglets with or without diarrhea, we found an unexpected decrease in the abundance of Candida tropicalis in diarrheal piglets. We also observed increased accumulation of reactive oxygen species (ROS) and the formation of neutrophil extracellular traps (NETs) in the colonic tissues of diarrheal piglets. Using dectin-1-knockout mice, we found that the over-accumulation of ROS killed C. tropicalis by promoting NET formation, which was dependent on dectin-1. The decreased abundance of C. tropicalis resulted in reduced phosphocholine consumption. Then, colonic phosphocholine accumulation drives water efflux by increasing cAMP levels by activating adenylyl cyclase, which promotes the clearance of pathogenic bacteria. Collectively, we demonstrated that phosphocholine is correlated with colonic C. tropicalis and promotes diarrhea and pathogen clearance. Our results suggest that mycobiota colonizing the colon might be involved in maintaining intestinal metabolic homeostasis through the consumption of certain metabolites.

The Xizi Pagoda (惜字塔) is a form of traditional religious building used for burning “Paper with Characters (字纸)”, worshiping the gods, praying for blessings, revitalzing culture, and it is also an important material embodiment in the process of the development and evolution of religion in China, carrying China’s unique “Scholarly Culture (书香文化)”. This paper is the first study of the philosophy of religion of Xizi Pagodas (a vernacular stone religious architectural landscape). The research of the representative Xizi Pagodas in different parts of Hunan province were carried out to analyze the origin of Xizi Pagodas, cultural rituals, modeling paradigms, decorative art, and to explore the traditional Chinese religious and philosophical thoughts embedded in Xizi Pagodas through relevant literatures. The results show that Xizi Pagodas contain the religious concepts of “Confucianism, Buddhism and Taoism (儒释道)”: the emergence of Xizi Pagodas is connected to the development of Confucianism; Xizi Pagodas incorporate Buddhistic thoughts and inherit architectural features of Buddhist Pagodas; and the “Xizi (惜字)” ritual and images of deities on Xizi Pagodas are associated with Taoism. At present, the number of Xizi Pagodas is decreasing, and the remaining ones are in a serious state of dilapidation and disrepair, and the “Xizi” Culture is gradually being forgotten and fading away. This paper enriches the relevant research on the Xizi Pagodas and the “Xizi” Culture.

ABSTRACTBacterial adhesion to dental materials’ surfaces is the initial cause of dental materials-related infections. Therefore, inhibiting bacterial adhesion is a critical step in preventing and controlling these infections. To this end, it is important to know how the properties of dental materials affect the interactions between microorganisms and material surfaces to produce materials without biological contamination. This manuscript reviews the mechanism of bacterial adhesion to dental materials, the relationships between their surface properties and bacterial adhesion, and the impact of bacterial adhesion on their surface properties. In addition, this paper summarizes how these surface properties impact oral biofilm formation and proposes designing intelligent dental material surfaces that can reduce biological contamination.

The mechanical washing wastewater contained a large amount of oil, and the iron wrapped in the oil was slowly released into water. This caused the effluent quality to fluctuate, causing common polymeric aluminum chloride (PAC) to ineffectively remove the water-in-oil. The method uses Ca2+ to demulsify and ClOx− to destroy the water-in-oil structure, which releases Fe from the oil droplets. The active oxygen produced by NaClOx further converts Fe2+ into Fe3+ and then combines with NaOH to form Fe(OH)3-flocs core, which improves the flocculation efficiency of PAC. The optimal ratio was approximately 400 μL of NaClOx, 200 μL of 1 mol L−1 CaO, and 12 mL of 12.8 g L−1 PAC. The oil removal rate reached 99.88% and the residue density was 178.42 mg L−1. The maximum Fe and chemical oxygen demand (COD) removal rates were close to 49.2 and 99.89%, respectively. In field applications, wastewater should be acidified first, and acidification oxidation is more effective than direct oxidation. In short, a novel way for treating mechanically washed wastewater with iron-in-oil characteristics by changing the environmental fate of iron is provided. HIGHLIGHTS 49.2% of Fe and 99.89% of COD were removed by NaClOx + CaO + PAC.; The optimal ratio was 400 μL of NaClOx, 200 μL of 1 mol L−1 CaO, and 12 mL of 12.8 g L−1 PAC.; NaClOx destroys the water-in-oil and alters the environmental fate of Fe to Fe(OH)3 for promoting flocculation.; Acidification prior to NaClOx oxidation benefits the removal of COD and iron.;

Abstract Background Spina bifida aperta (SBA) is a relatively common clinical type of neural tube defect. Although prenatal fetal surgery has been proven to be an effective treatment for SBA, the recovery of neurological function remains unsatisfactory due to neuron deficiencies. Our previous results demonstrated that intra-amniotic transplanted bone marrow mesenchymal stem cells (BMSCs) could preserve neural function through lesion-specific engraftment and regeneration. To further optimize the role of BMSCs and improve the environment of defective spinal cords so as to make it more conducive to nerve repair, the intra-amniotic transplanted BMSCs were modified with brain-derived neurotrophic factor (BDNF-BMSCs), and the therapeutic potential of BDNF-BMSCs was verified in this study. Methods BMSCs were modified by adenovirus encoding a green fluorescent protein and brain-derived neurotrophic factor (Ad-GFP-BDNF) in vitro and then transplanted into the amniotic cavity of rat fetuses with spina bifida aperta which were induced by all-trans-retinoic acid on embryonic day 15. Immunofluorescence, western blot and real-time quantitative PCR were used to detect the expression of different neuron markers and apoptosis-related genes in the defective spinal cords. Lesion areas of the rat fetuses with spina bifida aperta were measured on embryonic day 20. The microenvironment changes after intra-amniotic BDNF-BMSCs transplantation were investigated by a protein array with 90 cytokines. Results We found that BDNF-BMSCs sustained the characteristic of directional migration, engrafted at the SBA lesion area, increased the expression of BDNF in the defective spinal cords, alleviated the apoptosis of spinal cord cells, differentiated into neurons and skin-like cells, reduced the area of skin lesions, and improved the amniotic fluid microenvironment. Moreover, the BDNF-modified BMSCs showed a better effect than pure BMSCs on the inhibition of apoptosis and promotion of neural differentiation. Conclusion These findings collectively indicate that intra-amniotic transplanted BDNF-BMSCs have an advantage of promoting the recovery of defective neural tissue of SBA fetuses.

Phenolic compounds in oil wastewater are highly toxic and refractory. Hydrolysis at pH 12 for 12 h makes these compounds more vulnerable to attack and destruction. Under the binding and precipitation of polyaluminum chloride (PAC) at pH 8, the chemical oxygen demand (COD) was significantly reduced by 38%. The simulation found that hydrolysis + flocculation was a complex multistep process. The COD removal rate was mainly controlled by the prehydrolysis process. The metabolic pathway suggested that the m-cresol produced in the factory was oxidized to low water-soluble aldehyde. Alkaline hydrolysis converted the aldehyde into m-toluene-methanol, which was conducive to being captured by the PAC. Fourier transform infrared spectroscopy (FTIR) showed that the alkaline dehydrogenation of two m-methylphenyl carbinols produced a molecule that was removed by the resin. Generally, the particle size of the residue after alkaline hydrolysis was 6.4–8.3 nm, which was included in the pore size range of the resin. Therefore, the resin adsorption capacity for the hydrolyzed substances increased to 47,000 mg L−1, with 93% renewability. In short, hybrid technology reduces the concentration burden of the resin inflow and controls the molecular size of adsorbed substances for repurification. It strengthens the treatment effect of high COD wastewater and provides innovative ideas for extending the service life of resin.

Epidemiological studies show that obesity during pregnancy affects more than half of the pregnancies in the developed countries and is associated with obstetric problems and poor outcomes. Obesity tends to increase the incidence of complications. Furthermore, the resulting offspring are also adversely affected. However, the molecular mechanisms of obesity leading to poor pregnancy outcomes remain unclear. Omics methods are used for genetic diagnosis and marker discovery. The aim of this review was to summarize the maternal and fetal pathophysiological alterations induced by gestational obesity,identified using multi-omics detection techniques, and to generalize the biological functions and potential mechanisms of the differentially expressed molecules.

It is difficult to adjust the pH of oil acidized wastewater rich in Ca2+, thus hindering the polyacrylamide (PAM) flocculation. This study aims at accelerating the flocculation process by introducing CO2 into the water to induce the formation of CaCO3 nuclei. The order in which CO2 and NaOH were added affected the floc structures. Compared with CO2-NaOH-PAM, the flocs of NaOH-CO2-PAM were more compact and more CaCO3 crystals were formed. The aqueous Ca2+ involved in the reaction reached 20%, and CO2 utilization was enhanced. The settling time was shortened by half (from 20 to 3 min), and NaOH consumption was reduced by one-tenth (from 0.03 to 0.003 mol), hence significantly reducing the costs. Due to the higher settling rate and shorter contact time, the NaOH-CO2-PAM flocs adsorbed less so that the residual oil was 124 mg·L−1, while in the case of CO2-NaOH-PAM it was 88 mg·L−1. As a promising coagulation aid, CO2 can also be used to mineralize pollutants in wastewater.

The intestine requires a great deal of energy to maintain its health and function; thus, energy deficits in the intestinal mucosa may lead to intestinal damage. Aspartate (Asp) is an essential energy source in the intestinal mucosa and plays a vital part in gut health. In the current study, we hypothesized that dietary supplementation of Asp could alleviate DSS-induced colitis via improvement in the colonic morphology, oxidative stress, cell apoptosis, and microbiota composition in a mouse model of dextran. Asp administration decreased the disease activity index, apoptosis, myeloperoxidase, eosinophil peroxidase, and proinflammatory cytokine (IL-1β and TNF-α) concentrations in the colonic tissue, but improved the body weight, average daily food intake, colonic morphology, and antioxidant-related gene (GPX1 and GPX4) expression in DSS-treated mice. Expression levels of RIPK1 and RIPK3 were increased in the colon following Asp administration in the DSS-induced mice, whereas the MLKL protein expression was decreased. 16S rRNA sequencing showed that Asp treatment increased the abundance of Lactobacillus and Alistipes at the gene level, and Bacteroidetes at the phylum level, but decreased the abundance of Actinobacteria and Verrucomicrobia at the phylum level. Asp may positively regulate the recovery of DSS-induced damage by improving the immunity and antioxidative capacity, regulating RIPK signaling and modulating the gut microbiota composition.

The purpose of this study was to investigate the effect of okra polysaccharides with similar molecular weight on intestinal ecology. After extraction, ethanol precipitation, deproteinization and purification, two polysaccharide fractions, named as water-extracted polysaccharides (WEP) and alkaline-extracted polysaccharides (AEP), were obtained. According to the results of high performance liquid chromatography, AEP contained mannose, rhamnose, galacturonic acid and galactose, while WEP was composed of galactose, rhamnose, fructose, arabinose, glucose, galacturonic acid and mannose. The compositions of intestinal microbiota were affected by the change of daily substrates. Meanwhile, the concentration of ammonia and gastrointestinal transit time decreased, the total short chain fatty acid (SCFA) levels, moisture of caecum content increased. These findings suggested that the effect of okra polysaccharides on intestinal microbiota was achieved by the output of detrimental compounds and the supply of nutrients. Besides, AEP supported a more pivotal role in manipulating gut microbiota than WEP.

Background: Congenital malformations are common birth defects with high neonatal morbidity and mortality. It is essential to find simpler and more efficient biomarkers for early prenatal diagnosis. Therefore, we investigated PIWI-interacting RNAs (piRNAs) as potential prenatal biomarkers in plasma-derived exosomes from pregnant women carrying foetuses with congenital malformations. Methods: Small RNA sequencing was used to screen piRNA biomarkers in plasma-derived exosomes of five pregnant women carrying foetuses with nonsyndromic cleft lip and palate (nsCLP) and five women carrying normal foetuses. Differentially expressed piRNAs were verified in 270 pregnant women, including 111 paired women carrying foetuses with congenital malformations and normal foetuses (at 24 gestational weeks), 10 paired women carrying foetuses with nsCLP and normal foetuses (at 15–19 gestational weeks), and 28 women at different stages of normal pregnancy. piRNA biomarkers were also verified in placentas, umbilical cords, fetal medial calf muscles, and lip tissues of nsCLP and normal foetuses. Findings: We identified a biomarker panel of three pregnancy-associated exosomal piRNAs (hsa-piR-009228, hsa-piR-016659, and hsa-piR-020496) could distinguish nsCLP foetuses from normal foetuses. These three piRNAs had better diagnostic accuracy for nsCLP at the early gestational stage, at which time typical malformations were not detected upon prenatal ultrasound screening, and had diagnostic value for neural tube defects (NTDs) and congenital heart defects (CHDs). Interpretation: Our work revealed the potential clinical applications of piRNAs for predicting nsCLP, NTDs, and CHDs. Funding: National Key Research and Development Program, National Natural Science Foundation of China, and LiaoNing Revitalization Talents Program .

Background: Primary health institutions (PHIs) are the foundation of the whole health system and the basic link to achieve the goal of all people enjoying primary health care. However, the service capability of primary health institutions is not under the hierarchical medical system. Method: Data were collected from the China Health Statistics Yearbook between 2014 and 2020. PHIs included community health centres, community health stations, and township hospitals in our study. The service capability of primary health institutions was analysed from the perspective of structure, process, and results. Structure capability was evaluated using the number of beds, number of personnel, number of health technicians, and proportion of the number of personnel in PHIs accounting for the total number of health personnel. Process capability was evaluated using the number of general practitioners. The number of outpatients and inpatients, medical income, the proportion of drug income, and the average number of patients and beds served by physicians in PHIs per day were employed to evaluate the resulting capability. Results: From 2014 to 2020, the number of community health service centres/stations increased, while the number of township health centres decreased. In the aspect of structure capability, the total number of personnel and health technicians in community health centres/stations and township hospitals both increased during 2014 and 2020. However, the increasing rate in PHIs was a little bit less than that of general medical institutions. The proportion of male health technicians in community health centres and township hospitals both decreased, while the proportion of female technicians in both increased. From 2014 to 2020, the number of beds in PHIs also increased from 138.12 × 104 to 164.94 × 104. However, the proportion of beds in PHIs accounting for the total number of beds in medical institutions decreased. For the resulting capability, from 2014 to 2019, the proportion of diagnosis and treatment times in PHIs decreased from 57.41% to 51.96%, although it increased in 2020. The proportion of inpatients in PHIs decreased from 20.03% to 16.11%. From 2014 to 2020, the utilisation rate of hospital beds in PHIs decreased (from 55.6% to 34% for community health centres and 60.5% to 53.6% for township hospitals). The average daily bed days of doctors in township hospitals was higher than that of doctors in community health service centres. However, the average medical cost of outpatients and the per capita medical cost of inpatients in community health service centres were higher than in township hospitals. Conclusion: In recent years, although the service capability showed an increasing trend in PHIs, the growth rate was lower than the general health institutions. The utilisation rates of PHIs, including beds and physicians, were decreased. Among PHIs, the utilisation in township hospitals was higher than in community health centres with a relatively low price. Under the hierarchical medical system and normalisation period of the COVID-19 epidemic, it is important to improve the service capability to achieve its goal of increasing PHI utilisation and decreasing secondary and tertiary hospital utilisation.

Quiescin sulfhydryl oxidase (QSOX), present in a wide variety of eukaryotic species, catalyzes the insertion of disulfide bonds into unfolded, reduced proteins. Here we characterized the QSOX protein from the rodent malaria parasite Plasmodium berghei (PbQSOX), which is conserved in all sequenced malaria parasite species. The PbQSOX protein was not expressed in asexual erythrocytic stages, but was most abundantly expressed in ookinetes. Indirect immunofluorescence assays revealed PbQSOX was not only localized in cytoplasm of gametocytes, gametes and ookinetes, but also expressed on the surface of gametes and ookinetes. Western blot identified extracellular presence of PbQSOX in the culture medium of ookinetes suggestive of secretion. Pbqsox deletion (Δpbqsox) did not affect asexual intraerythrocytic development, but reduced exflagellation of male gametocytes as well as formation and maturation of ookinetes. Pbqsox deletion also led to a significant increase in the reduced thiol groups of ookinete surface proteins, suggesting that it may play a role in maintaining the integrity of disulfide bonds of surface proteins, which might be needed for ookinete development. Mosquitoes that fed on Δpbqsox-infected mice showed a significant reduction in ookinete and oocyst numbers compared to those fed on wild-type parasite-infected mice. Further, both polyclonal mouse antisera and a monoclonal antibody against the recombinant PbQSOX exhibited substantial transmission-blocking activities in in vitro and mosquito feeding assays, suggesting QSOX is a potential target for blocking parasite transmission.

Abstract Background A vaccine that targets multiple developmental stages of malaria parasites would be an effective tool for malaria control and elimination. Methods A conserved gene in Plasmodium, the Plasmodium berghei gene (PBANKA_020570) encoding a 51 kDa protein (pb51 gene), was identified through search of the PlasmoDB database using a combination of expression and protein localization criteria. A partial domain of the Pb51 protein was expressed in a prokaryotic expression system (rPb51) and used for immunization in mice. The protein expression profile and localization were studied by Western blot and indirect immunofluorescence assay (IFA), respectively. The inhibitory effect of the anti-rPb51 antibodies on parasite proliferation was evaluated in erythrocytes in vivo. The transmission-blocking activity of the immune sera was determined by in vitro ookinete conversion assay and by direct mosquito feeding assay (DFA). Results The rPb51 elicited specific antibodies in mice. Western blot confirmed Pb51 expression in schizonts, gametocytes and ookinetes. IFA showed localization of Pb51 on the outer membranes of schizonts, gametocytes, zygotes, retorts, ookinetes and sporozoites of P. berghei. Mice immunized with the rPb51 protein significantly reduced parasite proliferation and gametocyte conversion in vivo. Moreover, the rPb51 antisera also significantly reduced the in vitro ookinete conversion when added into the ookinete culture medium. In DFA, mice immunized with the rPb51 reduced the prevalence of mosquito infection by 21.3% and oocyst density by 54.8%. Conclusions In P. berghei, P51 was expressed in both asexual erythrocytic and sexual stages and localized on the surface of these stages with the exception of the ring stage. The anti-rPb51 antibodies inhibited both P. berghei proliferation in mice and transmission of the parasite to mosquitoes.

Selenoproteins mediate much of the cancer-preventive properties of the essential nutrient selenium, but some of these proteins have been shown to also have cancer-promoting effects. We examined the contributions of the 15kDa selenoprotein (Sep15) and thioredoxin reductase 1 (TR1) to cancer development. Targeted down-regulation of either gene inhibited anchorage-dependent and anchorage-independent growth and formation of experimental metastases of mouse colon carcinoma CT26 cells. Surprisingly, combined deficiency of Sep15 and TR1 reversed the anti-cancer effects observed with down-regulation of each single gene. We found that inflammation-related genes regulated by Stat-1, especially interferon-γ-regulated guanylate-binding proteins, were highly elevated in Sep15-deficient, but not in TR1-deficient cells. Interestingly, components of the Wnt/β-catenin signaling pathway were up-regulated in cells lacking both TR1 and Sep15. These results suggest that Sep15 and TR1 participate in interfering regulatory pathways in colon cancer cells. Considering the variable expression levels of Sep15 and TR1 found within the human population, our results provide insights into new roles of selenoproteins in cancer.

Background Although retinitis pigmentosa (RP) is the most common type of hereditary retinal dystrophy, approximately 25%-45% of cases remain without a molecular diagnosis. von Willebrand factor A domain containing 8 (VWA8) encodes a mitochondrial matrix-targeted protein; its molecular function and pathogenic mechanism in RP remain unexplained. Methods Family members of patients with RP underwent ophthalmic examinations, and peripheral blood samples were collected for exome sequencing, ophthalmic targeted sequencing panel and Sanger sequencing. The importance of VWA8 in retinal development was demonstrated by a zebrafish knockdown model and cellular and molecular analysis. Results This study recruited a Chinese family of 24 individuals with autosomal-dominant RP and conducted detailed ophthalmic examinations. Exome sequencing analysis of six patients revealed heterozygous variants in VWA8, namely, the missense variant c.3070G>A (p.Gly1024Arg) and nonsense c.4558C>T (p.Arg1520Ter). Furthermore, VWA8 expression was significantly decreased both at the mRNA and protein levels. The phenotypes of zebrafish with VWA8 knockdown are similar to those of clinical individuals harbouring VWA8 variants. Moreover, VWA8 defects led to severe mitochondrial damage, resulting in excessive mitophagy and the activation of apoptosis. Conclusions VWA8 plays a significant role in retinal development and visual function. This finding may provide new insights into RP pathogenesis and potential genes for molecular diagnosis and targeted therapy. [ABSTRACT FROM AUTHOR]