Study on the mechanism of hirudin multi target delaying renal function decline in chronic kidney disease based on the "gut-kidney axis" theory.

The disorder of the "gut-kidney axis" exacerbates renal function decline in chronic kidney disease (CKD), and current CKD therapy is insufficient to address this issue. Hirudin has a palliative effect on the decline of renal function. However, whether hirudin can delay CKD by regulating the "intestinal renal axis" disorder remains unclear. Unilateral ureteral ligation (UUO) induced CKD rat model, and the rats were treated with bifidobacterium and hirudin for 36 days. After 14 and 36 days of modeling, kidney and colon tissues were collected for pathology, western blot (WB) assay, and quantitative real-time PCR (qPCR) detection. Serum samples were collected for renal function testing. Fecal samples were used for 16S rRNA sequencing and research on fecal bacterial transplantation. Lipopolysaccharide combine with adenosine 5'-triphosphate (LPS + ATP)-induced intestinal epithelial cell injury was treated with a nod-like receptor pyrin domain-associated protein 3 (NLRP3) inhibitor and hirudin. Protein expression was detected using WB and qPCR. The kidneys and colons of the CKD rats exhibited varying degrees of lesions. Creatinine (CRE), blood urea nitrogen (BUN), N-acetyl-ß-D-glucosidase (NAG) enzyme, and serum uremic toxins were elevated. The expression of claudin-1 and occludin was decreased, NLRP3 inflammatory-related proteins were increased, and the gut microbiota was disrupted. These pathological changes were more pronounced after 36 days of modeling. Meanwhile, high-dose hirudin treatment significantly improved these lesions and restored the intestinal flora to homeostasis in CKD rats. In vitro, hirudin demonstrated comparable effects to NLRP3 inhibitors by upregulating claudin-1 and occludin expression, and downregulating NLRP3 inflammatory-related proteins expression. The dysbiosis of the gut microbiota and impaired intestinal epithelial barrier function in CKD are associated with renal dysfunction in CKD. Hirudin delays the progression of CKD by regulating the disorder of the "gut-kidney axis" and inhibiting the activation of the NLRP3-ASC-caspase-1 pathway.

Single-double-band switchable optical circular polarizers based on surface plasmon resonance: publisher's note.

This publisher's note reports a correction in Appl. Opt.63, 1153 (2024)APOPAI0003-693510.1364/AO.513837.

Single-double-band switchable optical circular polarizers based on surface plasmon resonance.

A single-double-band switchable circular polarization filter based on surface plasmon resonance exhibits significant potential for applications in fields such as communication and sensing due to its adjustable, low-cost, and easy integration features. In this study, we propose a bi-layer rod nanostructure and use FEM simulation to study the transmission spectra of the structure. The results demonstrate that the structure exhibits both single- and double-band circular polarization filtering effects, which can be switched by varying geometric parameters such as the distance between the two layers and the width of nanorods. Furthermore, the filtering effects of both single- and double-band are highly dependent on the length of the nanorods, with average extinction rates reaching 486 and 2020/129, respectively; the operating bandwidths (defined as extinction ratio >10) can reach 170 nm and 35 nm/70 nm, respectively. The underlying physical mechanisms are clarified by analyzing the electric dipole, magnetic dipole resonance modes, and induced chiral fields on nanostructures.

Intranasal drug delivery: The interaction between nanoparticles and the nose-to-brain pathway.

Intranasal delivery provides a direct and non-invasive method for drugs to reach the central nervous system. Nanoparticles play a crucial role as carriers in augmenting the efficacy of brain delivery. However, the interaction between nanoparticles and the nose-to-brain pathway and how the various biopharmaceutical factors affect brain delivery efficacy remains unclear. In this review, we comprehensively summarized the anatomical and physiological characteristics of the nose-to-brain pathway and the obstacles that hinder brain delivery. We then outlined the interaction between nanoparticles and this pathway and reviewed the biomedical applications of various nanoparticulate drug delivery systems for nose-to-brain drug delivery. This review aims at inspiring innovative approaches for enhancing the effectiveness of nose-to-brain drug delivery in the treatment of different brain disorders.

Matrix Metalloproteinase-Responsive Drug Delivery Systems.

Matrix metalloproteinases (MMPs) are a class of endopeptidases that are dependent on zinc and facilitate the degradation of extracellular matrix (ECM) proteins, thereby playing pivotal parts in human physiology and pathology. MMPs regulate normal tissue and cellular functions, including tissue development, remodeling, angiogenesis, bone formation, and wound healing. Several diseases, including cancer, inflammation, cardiovascular diseases, and nervous system disorders, have been linked to dysregulated expression of specific MMP subtypes, which can promote tumor progression, metastasis, and inflammation. Various MMP-responsive drug delivery and release systems have been developed by harnessing cleavage activities and overexpression of MMPs in affected regions. Herein, we review the structure, substrates, and physiological and pathological functions of various MMPs and highlight the strategies for designing MMP-responsive nanoparticles to improve the targeting efficiency, penetration, and protection of therapeutic payloads.

Maternal genetic intergenerational and transgenerational effects on hormone synthesis in ovarian granulosa cells of offspring exposed to cadmium during pregnancy.

This study aimed to investigate the maternally inherited intergenerational and transgenerational effects of cadmium (Cd) exposure on steroid hormone synthesis in the ovarian granulosa cells (GCs) of offspring rats. F1 rats were obtained by mating adult female Sprague-Dawley rats with healthy adult male rats and were exposed to 0, 0.5, 2.0, and 8.0 mg/kg CdCl2 during pregnancy. The adult female rats (PND 56) were mated with healthy adult male rats to produce F2 and F3 rats. The serum progesterone (Pg) and estradiol (E2) levels of the F2 adult female rats were decreased, while those of F3 rats were significantly increased. Moreover, hormone synthesis-related genes had different expression patterns in the F2 and F3 generations. F2 and F3 rat ovarian GCs exhibited altered miRNA expression profiles and DNA methylation patterns. Validation of miRNAs that regulate hormone synthesis-related genes in the cAMP/PKA signaling pathway suggested that miR-124-3p was downregulated in F2 and F3 rats, while miR-133a-5p and miR-150-5p were upregulated in F2 rats and downregulated in F3 rats. In summary, 1) there are maternal genetic intergenerational (GCs hormone synthesis disorder) and transgenerational (GCs hormone synthesis function repair change) effects on hormone synthesis function changes in offspring GCs induced by Cd exposure during pregnancy. 2) Changes in miRNAs and DNA methylation modifications associated with the genetic effects of altered hormone synthesis function in offspring GCs induced by Cd exposure during pregnancy are important. 3) Under the current environmental level of Cd exposure, the possible risk of maternal genetic intergenerational and transgenerational effects of offspring ovarian toxicity should be strongly considered.

Study on Production Technology and Volatile Flavor Analysis of Fragrance Zanthoxylum Seasoning Oil.

Dried green pepper and first-grade extracted soybean oil were selected as raw materials to study the effect of the Maillard reaction and cold-pressed compound on the quality of Zanthoxylum seasoning oil and its aroma-enhancing effect. The results showed that the optimal technology was as follows: the ratio of material to liquid was 1:5, the heating temperature was 110 °C, the reaction time was 25 or 30 min, and the addition of reducing sugar was 2%. The optimum ratio of fragrant Zanthoxylum seasoning oil was 1:7 for cold pressing oil and hot dipping oil. Compared with Zanthoxylum seasoning oil, it is based on the Maillard reaction and had a more intense and persistent aroma. The taste of fragrant Zanthoxylum seasoning oil was the best of the three blended oils. The possible types of volatile flavor compounds in the three kinds of Zanthoxylum seasoning oils detected by Heracles II ultra-fast gas phase electronic nose were, respectively, 16, 19, and 15. Among the three kinds of Zanthoxylum seasoning oils, the content of limonene, linalool, Eucalyptol, n-pentane α-Pinene, myrcene, and phellandrene was more abundant, which indicated that olefins and alcohols contributed more to the overall flavor of the three kinds of Zanthoxylum seasoning oils.

Multigenerational genetic effects of paternal cadmium exposure on ovarian granulosa cell apoptosis.

To explore whether paternal cadmium (Cd) exposure causes ovarian granulosa cell (GC) apoptosis in offspring and the multigenerational genetic effects. From postnatal day 28 (PND28) until adulthood (PND56), SPF male Sprague-Dawley (SD) rats were gavaged daily with varying concentrations of CdCl2. (0, 0.5, 2, and 8 mg/kg). After treatment, the F1 generation was produced by mating with untreated female rats, and the F1 generation male rats were mated with untreated female rats to produce the F2 generation. Apoptotic bodies (electron microscopy) and significantly higher apoptotic rates (flow cytometry) were observed in both F1 and F2 ovarian GCs following paternal Cd exposure. Moreover, the mRNA (qRTPCR) or protein (Western blotting) levels of bax, bcl2, bcl-xl, caspase 3, caspase 8, and caspase 9 were changed to varying degrees. Apoptosis-related miRNAs (qRTPCR) and methylation modifications of apoptosis-related genes (bisulfite-sequencing PCR) in ovarian GCs were further detected. Compared with those of controls, the expression patterns of miRNAs in F1 and F2 offspring were different after paternal Cd exposure, while the average methylation level of apoptosis-related genes did not change significantly (except for individual loci). In summary, there are paternal genetic intergenerational and transgenerational effects on ovarian GC apoptosis induced by paternal Cd exposure. These genetic effects were related to the upregulation of BAX, BCL-XL, Cle-CASPASE 3, and Cle-CASPASE 9 in F1 and the upregulation of Cle-CASPASE 3 in F2 progeny. Important changes in apoptosis-related miRNAs were also observed.

Paternal genetic effects of cadmium exposure during pregnancy on hormone synthesis disorders in ovarian granulosa cells of offspring.

The aim of this study was to investigate the paternal genetic intergenerational and transgenerational genetic effects of cadmium (Cd) exposure during pregnancy on estradiol (E2) and progesterone (Pg) synthesis in the ovarian granulosa cells (GCs) of offspring. Pregnant SD rats were intragastrically exposed to CdCl2 (0, 0.5, 2.0, 8.0 mg/kg) from days 1 to 20 to produce the F1 generation, F1 males were mated with newly purchased females to produce the F2 generation, and the F3 generation was obtained in the same way. Using this model, Cd-induced hormone synthesis disorders in GCs of F1 have been observed [8]. In this study, altered serum E2 and Pg levels in both F2 and F3 generations showed a nonmonotonic dose‒response relationship. In addition, hormone synthesis-related genes (Star, Cyp11a1, Cyp17a1, Cyp19a1, Sf-1) and miRNAs were observed to be altered in both F2 and F3. No differential changes in DNA methylation modifications of hormone synthesis-related genes were observed, and only the Adcy7 was hypomethylated. In summary, paternal genetic intergenerational and transgenerational effects exist in ovarian GCs E2 and Pg synthesis disorders induced by Cd during pregnancy. In F2, the upregulation of StAR and CYP11A1, and changes in the miR-27a-3p, miR-27b-3p, and miR-146 families may be important, while changes in the miR-10b-5p and miR-146 families in F3 may be important.

Ionic Liquids as Promisingly Multi-Functional Participants for Electrocatalyst of Water Splitting: A Review.

Ionic liquids (ILs), as one of the most concerned functional materials in recent decades, have opened up active perspectives for electrocatalysis. In catalyst preparation, ILs act as characteristic active components besides media and templates. Compared with catalysts obtained using ordinary reagents, IL-derived catalysts have a special structure and catalytic performance due to the influence of IL's special physicochemical properties and structures. This review mainly describes the use of ILs as modifiers and reaction reagents to prepare electrocatalysts for water splitting. The designability of ILs provides opportunities for the ingenious composition of cations or anions. ILs containing heteroatoms (N, O, S, P, etc.) and transition metal anion (FeCl4-, NiCl3-, etc.) can be used to directly prepare metal phosphides, sulfides, carbides and nitrides, and so forth. The special physicochemical properties and supramolecular structures of ILs can provide growth conditions for catalysts that are different from the normal media environment, inducing special structure and high performance. ILs as heteroatom sources are safe, green and easy to operate compared with traditional heteroatom sources. The strategy for using ILs as reagents is expected to realize 100% atomic transformation of reactants, in line with the concept of green chemistry. This review reflects the discovered work with the best findings from the literature. It will offer readers a deeper understanding on the development of IL-derived electrocatalysts and inspire them to ingeniously design high-performance electrocatalysts for water splitting.

Paternal genetic intergenerational and transgenerational effects of cadmium exposure on hormone synthesis disorders in progeny ovarian granulosa cells.

To investigate the paternal genetic effects of cadmium (Cd) exposure on hormone synthesis disorders in the ovarian granulosa cells (GCs) of offspring. Here, male Sprague‒Dawley (SD) rats were gavaged with CdCl2 (0, 0.5, 2, 8 mg/kg) from postnatal day (PND) 28-56, followed by mating with newly purchased healthy adult females to produce F1, and F1 adult males (PND 56) were mated with newly purchased healthy adult females to produce F2. The serum levels of estradiol (E2) and progesterone (Pg) decreased in F1 but essentially returned to normal in F2. The levels of StAR, CYP11A1, CYP17A1, CYP19A1, and SF-1 showed different alterations in F1 and F2 ovarian GCs. The expression patterns of miRNAs and imprinted genes related to hormone synthesis in GCs of F1 and F2 differed, but methylation of hormone synthesis-related genes was not significantly altered (except for individual loci in F1). In addition, there were significant changes in the expression of imprinted genes and miRNAs in F0 and F1 sperm. We conclude that paternal Cd exposure causes intergenerational genetic effects (hormone synthesis disorders) and transgenerational effects (reparative changes in hormone synthesis function) in ovarian GCs. These genetic effects were related to the downregulation of StAR in F1 and the upregulation of CYP17A1, CYP19A1, StAR and SF-1 in F2. Important changes in miRNAs and imprinted genes were also observed, but not all alterations originated from paternal inheritance.

Deep Eutectic Solvent-Mediated Electrocatalysts for Water Splitting.

As green, safe, and cheap solvents, deep eutectic solvents (DESs) provide tremendous opportunities to open up attractive perspectives for electrocatalysis. In this review, the achievement of DESs in the preparation of catalysts for electrolytic water splitting is described in detail according to their roles combined with our own work. DESs are generally employed as green media, templates, and electrolytes. A large number of hydrogen bonds in DESs result in supramolecular structures which have the ability to shape the morphologies of nanomaterials and then tune their performance. DESs can also serve as reactive reagents of metal electrocatalysts through directly participating in synthesis. Compared with conventional heteroatom sources, they have the advantages of high safety and designability. The "all-in-one" transformation strategy is expected to realize 100% atomic transformation of reactants. The aim of this review is to offer readers a deeper understanding on preparing DES-mediated electrocatalysts with higher performance for water splitting.

Genetically predicted phosphate and cardiovascular disease: A Mendelian randomization study.

Background: Extensive epidemiological studies have highlighted the correlation between serum phosphate and cardiovascular diseases. The present study aims to determine whether genetically predicted serum phosphate is causally associated with the distinct subtypes of cardiovascular events through the use of Mendelian randomization (MR) analysis. Methods: Independent and strongly correlated single-nucleotide polymorphisms (SNPs) for serum phosphate were extracted from publicly available genome-wide association studies. Summary statistics of cardiovascular diseases were derived from large-scale consortiums, including HERMES and FinnGen biobank. MR-Egger, weighted median, inverse variance weighted, pleiotropy residual sum and outlier (MR-PRESSO) methods and MR using robust adjusted profile score (MR-RAPS) were employed to analyze causality. The sensitivity analyses comprised heterogeneity, horizontal pleiotropy, and leave-one-out approaches; these were used to ensure the stability of the results. Results: Our study demonstrated that increased genetically predicted serum phosphate is causally associated with a higher risk of valvular heart disease (VHD) [For VHD including rheumatic fever: odds ratio (OR) = 2.45; 95% confidence interval (CI), 1.52-3.94; p = 0.0002; for non-rheumatic VHD: OR = 6.58; 95% CI, 2.50-17.32; p = 0.0001]. However, no causal association was detected between serum phosphate and other common cardiovascular diseases (including coronary heart disease, heart failure, atrial fibrillation, and essential hypertension). Conclusions: The results indicate strong causality between serum phosphate and valvular heart disease. Serum phosphate-lowering therapy within the physiological range may represent a novel therapeutic method for valvular heart disease.

High-dimensional Single-cell Analysis Delineates Peripheral Immune Signature of Coronary Atherosclerosis in Human Blood.

Rationale: Pathogenesis of human coronary atherosclerosis is tightly associated with the imbalance of inflammation and resolution in the local immune microenvironment of AS plaques. However, how the peripheral immune system dynamically changes along with disease progression in humans remains unclear. As a result, the minimally-invasive clinical biomarkers that can sensitively distinguish different stages of human coronary atherosclerosis are still lacking. Methods: We performed single-cell Cytometry by Time-Of-Flight (CyTOF) analyses to comprehensively profile the compositions and phenotypes of CD45+ cells derived from 83 human peripheral blood samples with two independent antibody-staining panels (T cell panel and myeloid cell panel). Clinical associations between the frequencies of peripheral immune cell subsets with AS plaque burdens of coronary arteries (Gensini score) and serum lipids were also examined. By integrating immune and clinical features, we established novel CVD risk prediction models to stratify patients in different disease stages. Results: We revealed the disease stage-associated peripheral immune features for patients with coronary atherosclerosis (CAS) and atherosclerotic cardiovascular disease (ASCVD), and also identified the specific peripheral immune cell subsets that were tightly associated with the disease severity of coronary arteries (Gensini score). By integrating these peripheral immune signatures with clinical features, we have established a disease progression prediction (DPP) model that could precisely discriminate CAS patients from ASCVD patients with high prediction accuracy (ROC-AUC = 0.88). Conclusion: The progression of coronary atherosclerosis is accompanied by significant alterations of the peripheral immune system, including the changes in the distributions as well as phenotypic functions of specific immune cell subsets. The indicated stage-specific peripheral immune signatures thus become promising minimally-invasive liquid biomarkers that could help to potentially diagnose and monitor the CVD progression in humans.

Fertility intentions among young people in the era of China's three-child policy: a national survey of university students.

BACKGROUND: This study aimed to assess the fertility intentions of young people after the announcement of the three-child policy in China and to determine whether knowledge about reproductive, maternal, newborn, and child health (RMNCH) services or support, childbearing- and childbirth-related anxiety, and parenthood-related anxiety influence fertility intentions. METHODS: A cross-sectional Internet-based survey was conducted on a nationwide sample of young people aged 18 to 28 years old in education institutions. Factors associated with fertility intentions were analysed using partial least squares structural equation modelling (PLS-SEM). RESULTS: Only 4.2% of males and 1.7% of females intended to have three children or more. On the whole, the majority (40.3%) reported the intention to have two children. The mean and standard deviation (SD) for the total knowledge RMNCH support and/or services knowledge score was 9.5 (SD ± 8.9), out of a possible score of 39. The median and interquartile range (IQR) of childbearing- and childbirth-related anxiety score was 8.0 (IQR = 6.0-9.0), out of a possible score of 10. The median and IQR of parenthood-related anxiety score among the males was 6.0 (IQR = 4.0-9.0) and for females was 7.0 (IQR = 5.0-9.0). Results from PLS-SEM revealed that a higher level of knowledge of RMNCH support and/or services is significantly associated with higher fertility intentions. Both childbearing- and childbirth-related anxiety and parenthood-related anxiety were inversely associated with fertility intentions. CONCLUSION: Raising awareness about RMNCH supportive measures and easing birth- and parenting anxiety are imperative to enhance birth rates. Future policies should pay more attention to these determinants to achieve their intended goal of boosting population growth.

Revision of the non-suicidal self-injury behavior scale for adolescents with mental disorder. / åº”ç”¨äºŽé’å°‘å¹´ç²¾ç¥žéšœç¢æ‚£è€ çš„éžè‡ªæ€æ€§è‡ªä¼¤è¡Œä¸ºé‡è¡¨ä¿®è®¢.

OBJECTIVES: Adolescents are at high risk of non-suicidal self-injury (NSSI). Currently, there is no clinical assessment tool for adolescent NSSI behaviors measurement with global consistency. The Ottawa Self-injury Inventory (OSI) is considered as a relatively comprehensive assessment tool for NSSI, but the questionnaire is discussed with excessive content and timecostly, which may affect the reliability of the measurement results for adolescent.Thus, this study, based on OSI, aims to revise the assessment tool for adolescent with NSSI that is suitable for both clinically and scientifically, referring to the diagnostic criteria for NSSI in the 5th Diagnostic and Statistical Manual of Mental Disorder (DSM-5). METHODS: This study was led by the Second Xiangya Hospital of Central South University and collaborated with 6 mental health service institutions in China from August to December 2020. Adolescent aged from 12 to 24 years old who had self-injury behavior and met the DSM-5 diagnostic criteria for NSSI were continuously recruited in the psychiatric outpatient department or ward. After clinical diagnosis by an experienced attending psychiatrist or above, the general information and OSI were collected by questionnaires. SPSS 24.0 and AMOS structural equation model statistical softwares were used to conduct item analysis and exploratory factor analysis on the obtained data to complete the revision of the scale. Cronbach's alpha coefficient, split-half reliability, test-retest reliability, and content validity and structure validity were performed to analyze the reliability and validity and confirmatory factor analysis was carried out to test the structure validity for the revised scale. RESULTS: A total of 234 adolescent with NSSI were enrolled, including 33 (14.1%) males and 201 (85.9%) females with the mean age of (16.2±2.6) years old. The most common clinical diagnoses were depression disorder (57.4%), bipolar disorder (20.9%), adolescent mood disorder (17.1%), etc. Nine items (item 2, 7, 11, 13, 23, 24, 10, 17, 18) in the functional scale of OSI were deleted according to extreme grouping method, correlation analysis, and principal component analysis in exploratory factor analysis. The revised functional scale for NSSI consisted of 15 items. The reliability analysis showed that the Cronbach's alpha coefficients of NSSI thought and behavior frequency, addiction characteristics, and function scales were 0.799, 0.798, and 0.835, respectively, and the split-half coefficients were 0.714, 0.727, and 0.852, respectively. The test-retest coefficients of the latter 2 scales were 0.466 and 0.560, respectively. The correlation coefficient between sub-items and total scores in each part of the scale showed good content validity. The exploratory factor analysis showed that a component was extracted from the frequency of thoughts and behaviors of NSSI, one component was extracted from the addictive characteristics, and three components were extracted from the functional part. The three functional subscales were social influence, external emotion regulation, and internal emotion regulation. The factor load of each item was >0.400. CONCLUSIONS: The revised Chinese version OSI targeted the adolescent patients with mental disorders has relatively ideal reliability and validity. The scale shows high stability, dependability, and a reasonable degree of fit. It is a suitable assessment tool for clinical and scientific research on adolescent with NSSI.

Maternal genetic effect on apoptosis of ovarian granulosa cells induced by cadmium.

To investigate the maternal genetic effects of cadmium (Cd) -induced apoptotic in ovarian granulosa cells (OGCs). Herein, pregnant Sprague-Dawley (SD) rats were treated with CdCl2 from day 1 to day 20, F1 and F2 female rats were mated with untreated males to produce F2 and F3 generations. Under this model, significant apoptotic changes were observed in F1 OGCs induced by Cd (Liu et al., 2021). In this study, no apoptotic bodies were found in F2 while the mitochondrial membrane potential level decreased significantly but not in F3. Moreover, significant changes in bcl-xl and Cle-CASPASE-9/Pro-CASPASE-9 ratio were observed in F2 which disappears in F3. The DNA methylation sequencing and microRNAs (miRNAs) microarray reveals different gene methylation and miRNAs changes in F2 and F3. Notably, miR-132-3p, miR-199a-5p, and miR-1949 were upregulated in F1 while downregulated in F2 and F3 in which apoptosis gradually disappeared. Further, miRNA maturation-related genes and transcription factors have different expression patterns in F1-F3. These results indicate that maternal genetic intergenerational/transgenerational effect of Cd-induced OGCs apoptotic was significantly attenuated and disappeared, which was related to self-repair regulation of apoptosis-related genes. The changes in apoptosis-related miRNAs and DNA methylation may be important, and the role of transcription factors deserve attention.