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.

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.

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.

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.

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.

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.

Cadmium disrupts mouse embryonic stem cell differentiation into ovarian granulosa cells through epigenetic mechanisms.

Cadmium (Cd) can influence germ cell development, and epigenetic events may be involved. However, there is no study on whether Cd can influence germ cells differentiation into ovarian granulosa cells (GCs), and more insight into the molecular mechanism of the effect of Cd on germ cell development from mouse embryonic stem (ES) cells into ovarian granulosa cells and investigation of appropriate epigenetic factors are of great importance. In this study, mouse ES cell differentiation into GCs was established in an in vitro model. Subsequently, different Cd concentrations of 0, 0.1, 0.3, and 1 and then 3.0, and 10.0 µmol/L were cultured in this in vitro model. We demonstrated that Cd treatment can interrupt ES cell differentiation into GCs by morphology and ultrastructure observation. Four specific markers (octamer-binding transcription factor 4 (OCT4), sex-determining region Y-box 2 (SOX2), Nanog homeobox (Nanog), and Anti-müllerian hormone type II receptor (Amhr2)) were significantly changed as measured by quantitative real-time-PCR or Western blot (p < 0.05). Cd also significantly changed the DNA methylation of GC sites on the CpG island of Nanog according to the sequential mass ARRAYR methylation method (p < 0.05). The MeRIP-qPCR method was used to detect the levels of N6-methyladenosine (m6A) methylation modification of long noncoding RNA (lncRNA) 1281 and indicated that they were decreased (p < 0.05). Microarray chip analysis, miRNA screening, and bioinformatics were used to further explore the roles of marker regulation-related miRNAs, and 27 miRNAs were putatively related to Cd-interrupted differentiation in ES cells. These data indicated that Cd can interrupt ES cell differentiation into GCs and affect germ cell development, and the underlying mechanism may involve epigenetic mechanisms.

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.

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.

C-myc promotes miR-92a-2-5p transcription in rat ovarian granulosa cells after cadmium exposure.

Cadmium (Cd) can induce ovarian injury by microRNAs (miRNAs), however, the molecular mechanism of miRNAs after Cd exposure have not known. In this study, 56-day-old adult female Sprague-Dawley (SD) rats were injection with PMSG, after 48 h, ovarian granulosa cells (GCs) were extracted and cultured for 24 h, then treated with 0, 2.5, 5, 10 and 20 µM Cd for 24 h. The results showed that expression levels of miR-92a-2-5p (upregulated) and Bcl2 (downregulated) changed significantly after Cd exposure. The messenger RNA (mRNA) and protein expression levels of DNMT1, DNMT3A, and DNMT3B had changed, but no obvious differences were found in miR-92a-2-5p single site methylation. The transcription factors C-MYC (upregulated), E2F1 (downregulated), and SP1 (downregulated), which target miRNAs significantly changed after exposure to Cd. The human ovarian GC tumor line (COV434) was used to knocked down C-myc, and the expression of miR-92a-2-5p was downregulated in the COV434-C-myc + 10 µM Cd group compared with COV434 cells. The N6-methyladenosine (m6A) methylation modification levels of long noncoding RNA (lncRNA) MT1JP and lncRNA CDKN2B-AS, which regulate miR-92a-2-5p were detected. In the 10 µM Cd group, m6A methylation levels at MT1JP-84, CDKN2B-AS-257, and CDKN2B-AS-329 were reduced. In summary, after Cd exposure, expression of miR-92a-2-5p, which targets the antiapoptotic gene Bcl2, was upregulated, which may be primarily related to upregulation of C-myc. MiR-92a-2-5p promoter DNA methylation may has no obvious effect on miR-92a-2-5p. Otherwise, the role of m6A methylation modified lncRNA MT1JP and lncRNA CDKN2B-AS in the regulation of miR-92a-2-5p needs further study.

Structural basis underlying the electron transfer features of a blue copper protein auracyanin from the photosynthetic bacterium Roseiflexus castenholzii.

Auracyanin (Ac) is a blue copper protein that mediates the electron transfer between Alternative Complex III (ACIII) and downstream electron acceptors in both fort chains of filamentous anoxygenic phototrophs. Here, we extracted and purified the air-oxidized RfxAc from the photoheterotrophically grown Roseiflexus castenholzii, and we illustrated the structural basis underlying its electron transferring features. Spectroscopic and enzymatic analyses demonstrated the reduction of air-oxidized RfxAc by the ACIII upon oxidation of menaquinol-4 and menaquinol-7. Crystal structures of the air-oxidized and Na-dithionite-reduced RfxAc at 2.2 and 2.0 Å resolutions, respectively, showed that the copper ions are coordinated by His77, His146, Cys141, and Met151 in minor different geometries. The Cu1-Sδ bond length increase of Met151, and the electron density Fourier differences at Cu1 and His77 demonstrated their essential roles in the dithionite-induced reduction. Structural comparisons further revealed that the RfxAc contains a Chloroflexus aurantiacus Ac-A-like copper binding pocket and a hydrophobic patch surrounding the exposed edge of His146 imidazole, as well as an Ac-B-like Ser- and Thr-rich polar patch located at a different site on the surface. These spectroscopic and structural features allow RfxAc to mediate electron transfers between the ACIII and redox partners different from those of Ac-A and Ac-B. These results provide a structural basis for further investigating the electron transfer and energy transformation mechanism of bacterial photosynthesis, and the diversity and evolution of electron transport chains.

A new phosphonium-based ionic liquid to synthesize nickel metaphosphate for hydrogen evolution reaction.

The electrochemical hydrogen evolution reaction (HER) is a promising strategy for production of hydrogen; however, it is still restricted by appropriate efficient and low-cost electrocatalysts. Herein, for the first time, the n-octylammonium hypophosphite, a kind of protic ionic liquid (IL), was used as a new phosphorus source for the manufacture of nickel metaphosphate (Ni2P4O12) electrocatalysts. In contrast to traditional multi-step fabrication processes, the n-octylammonium hypophosphite acted as both reactant and solvent to synthesize Ni2P4O12 by a one-step calcination approach. The obtained Ni2P4O12 as an alkaline HER catalyst required a low overpotential of 116 mV at -10 mA cm-2 and a small Tafel slope of 97 mV dec-1, comparable to the majority of reported Ni-based materials and other phosphate catalysts. Furthermore, this catalyst exhibited robust stability with no distinct attenuation of current density after a long-term durability test in 1 M KOH. Therefore, this task-specific IL strategy with a simple reaction system, reducing the occurrence of side reactions, provided a new perspective on design of high-efficiency metaphosphate electrocatalysts.

Cadmium exposure during prenatal development causes progesterone disruptors in multiple generations via steroidogenic enzymes in rat ovarian granulosa cells.

Exposure to the heavy metal cadmium (Cd) in the environment is linked to adverse health. To fully understand the adverse effects of this important endocrine-disrupting compound (EDC) requires studies that address multigenerational effects and epigenetic mechanisms. The present study orally dosed pregnant SD rats with Cd from gestation day 1 until birth. First filial generation (F1) female rats were mated with untreated males to generate the secondary filial generation (F2). Ovarian granulosa cells (OGCs) were collected at postnatal day (PND) 56 from both generations after prenatal Cd exposure, and hormone secretion examinations showed a progesterone disorder. Significant decreases in steroidogenic enzymes (steroidogenic acute regulatory protein (StAR) and P450 cholesterol side-chain cleavage enzyme (CYP11A1)) were observed in F1 and F2 rats. However, F1 and F2 rats had different patterns of mRNA and protein expression of steroidogenic factor 1 (SF-1). We also found that microRNAs were significantly changed using a microarray, and miR-10b-5p and miR-27a-3p were upregulated in F1 and F2 rats. The COV434 cell line microRNA-knockdown model showed that these two important microRNAs regulated the StAR-induced Cd effect on progesterone secretion. Overall, the results of this study indicate that prenatal Cd exposure causes cytotoxicity problems, progesterone disorder and microRNAs expression changed in a multigenerational manner. And progesterone disorder may interfere with the steroidogenic enzymes in offspring. The present study also revealed that environmental pollution produces multigenerational effects.

The C-terminal domain conformational switch revealed by the crystal structure of malyl-CoA lyase from Roseiflexus castenholzii.

Malyl-coenzyme A lyase (MCL) is a carbon-carbon bond lyase that catalyzes the reversible cleavage of coenzyme A (CoA) thioesters in multiple carbon metabolic pathways. This enzyme contains a CitE-like TIM barrel and an additional C-terminal domain that undergoes conformational changes upon substrate binding. However, the structural basis underlying these conformational changes is elusive. Here, we report the crystal structure of MCL from the thermophilic photosynthetic bacterium Roseiflexus castenholzii (RfxMCL) in the apo- and oxalate-bound forms at resolutions of 2.50 and 2.65 Å, respectively. Molecular dynamics simulations and structural comparisons with MCLs from other species reveal the deflection of the C-terminal domain to close the adjacent active site pocket in the trimer and contribute active site residues for CoA coordination. The deflection angles of the C-terminal domain are not only related to the occupation but also the type of bound substrates in the adjacent active site pocket. Our work illustrates that a conformational switch of the C-terminal domain accompanies the substrate-binding of MCLs. The results provide a framework for further investigating the reaction mechanism and multifunctionality of MCLs in different carbon metabolic pathways.

Three-Year Clinical Outcomes of a Polymer-Free Paclitaxel-Eluting Microporous Stent in Real-World Practice: Final Results of the Safety and Efficacy Registry of the Yinyi Stent (SERY-I).

BACKGROUND: The safety and efficacy of a China-made polymer-free paclitaxel-eluting microporous stent (Yinyi) at 1-year has been previously reported. However, limited evidence exists regarding the long-term performance of this novel drug-eluting stent (DES). This study investigated the 3-year efficacy and safety of the Yinyi stent in the setting of safety and efficacy registry of the Yinyi stent (SERY-I) clinical trial. METHODS: Between June 2008 and August 2009, a total of 1045 patients undergoing percutaneous coronary intervention (PCI) were implanted with ≥ 1 Yinyi stents at 27 medical centers in mainland China. Thereafter, clinical follow-up was performed for a period of 3 years after enrollment. The primary endpoint was the cumulative rate of composite major adverse cardiac events (MACE) including target lesion revascularization (TLR), the combined incidence of cardiac death, and non-fatal myocardial infarction; the second endpoint was the incidence of stent thrombosis. RESULTS: Overall, 1376 lesions were treated successfully with 1713 Yinyi stents, and 1019 (98.7%) patients received dual antiplatelet therapy for at least 12 months. At 3 years, a total of 13 (1.33%) patients had suffered cardiac death. The incidence of non-fatal myocardial infarction and TLR was 9 (0.92%) and 58 (5.92%) among the patients. Stent thrombosis occurred in 13 (1.33%) patients, and the rate of Academic Research Consortium (ARC) definite or probable stent thrombosis was 0.82%. CONCLUSIONS: Given the limitations that SERY-I was a single arm, nonrandomized study and only telephone follow-up was performed without angiographic analysis, the safety and efficacy of Yinyi stent observed in this extended follow-up Registry needs further verification.

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.

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.

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.