Nanoceria-induced variations in leaf anatomy and cell wall composition drive the increase in mesophyll conductance of salt-stressed cotton leaves.

Nanomaterials as an emerging tool are being used to improve plant's net photosynthetic rate (AN) when suffering salt stress, but the underlying mechanisms remain unclear. To clarify this, a hydroponic experiment was conducted to study the effects of polyacrylic acid coated nanoceria (PNC) on the AN of salt-stressed cotton and related intrinsic mechanisms. Results showed that the PNC-induced AN enhancement of salt-stressed leaves was strongly facilitated by the mesophyll conductance to CO2 (gm). Further analysis showed that the PNC-induced improvement of gm was related to the increased chloroplast surface area exposed to intercellular airspaces, which was attribute to the increased mesophyll surface area exposed to intercellular airspaces and chloroplast number due to the increased K+ content and decreased reactive oxygen species level in salt-stressed leaves. Interestingly, our results also showed that PNC-induced variations in cell wall composition of salt-stressed cotton leaves strongly influenced gm, especially, hemicellulose and pectin. Moreover, the proportion of pectin in cell wall composition played a more important role in determining gm. Our study demonstrated for the first time that nanoceria, through alterations to anatomical traits and cell wall composition, drove gm enhancement, which ultimately increased AN of salt-stressed leaves.

Regulatory Networks of Coresident Subgenomes during Rapid Fiber Cell Elongation in Upland Cotton.

Cotton, an intriguing plant species shaped by polyploidization, evolution, and domestication, holds particular interest due to the complex mechanisms governing fiber traits across its two subgenomes. However, the regulatory elements or transcriptional networks between subgenomes during fiber elongation remain elusive. Here, we analyzed 1,462 cotton fiber samples to reconstruct gene expression regulatory networks influencing fiber cell elongation. Inter-subgenomic eQTLs largely dictate gene transcription, with a notable tendency for the D subgenome to regulate A subgenome eGenes. This regulation showcases synchronized homoeologous gene expression driven by colocalized eQTLs and divergent patterns that diminish genetic correlations, thus leading to preferential expression in the A and D subgenomes. Hotspot456 emerged as a key regulator of fiber initiation and elongation, and artificial selection of trans-eQTLs in hotspot456 positively regulating KCS1 has facilitated cell elongation. To elucidate the roles of trans-eQTL in improved fiber breeding, experimentation confirmed the inhibition of GhTOL9 by a specific trans-eQTL via GhWRKY28, which negatively impacts fiber elongation. We propose a model where the GhWRKY28-GhTOL9 module, through the Endosomal Sorting Complex Required for Transport pathway, regulates this process. This research significantly advances our understanding of cotton's evolutionary, domestication processes, and the intricate regulatory mechanisms underlying significant plant traits.

Clonorchis sinensis infection induces pathological changes in feline bile duct epithelium and alters biliary microbiota composition.

BACKGROUND: Clonorchis sinensis is a zoonotic liver fluke that inhabits the bile ducts of the human liver for prolonged periods, leading to cholangiocarcinoma. Recent research indicates associations between altered biliary microbiota and bile duct disorders. However, the impacts of C. sinensis infection on bile duct epithelium and subsequent effects on biliary microbiota remain unknown. METHODS: Feline bile duct samples were collected from both uninfected and C. sinensis-infected cats. Histopathological examination was performed to assess epithelial changes, fibrosis, mucin and cell proliferation using hematoxylin-eosin staining and immunohistochemistry. Additionally, biliary microbiota composition was analyzed through 16S rRNA gene sequencing. Statistical analyses were conducted to compare the microbial diversity and relative abundance between infected and uninfected samples. RESULTS: Histopathological analysis of infected feline bile ducts revealed prominent epithelial hyperplasia characterized by increased cell proliferation. Moreover, periductal fibrosis and collagen fibrosis were observed in infected samples compared to uninfected controls. Biliary microbial richness decreased with disease progression compared to uninfected controls. Streptococcus abundance positively correlated with disease severity, dominating communities in cancer samples. Predictive functional analysis suggested that C. sinensis may promote bile duct lesions by increasing microbial genes for carbohydrate metabolism, replication, and repair. CONCLUSIONS: This study provides comprehensive insights into the pathological effects of C. sinensis infection on feline bile duct epithelium and its influence on biliary microbiota composition. These novel findings provide insight into C. sinensis pathogenesis and could inform therapeutic development against human clonorchiasis. Further research is warranted to elucidate the underlying mechanisms driving these changes and their implications for host-parasite interactions.

Title: L'infection par Clonorchis sinensis induit des changements pathologiques dans l'épithélium des voies biliaires félines et modifie la composition du microbiote biliaire. Abstract: Contexte : Clonorchis sinensis est une douve zoonotique du foie qui habite les voies biliaires du foie humain pendant des périodes prolongées, conduisant au cholangiocarcinome. Des recherches récentes indiquent des associations entre une altération du microbiote biliaire et des pathologies des voies biliaires. Cependant, les impacts de l'infection par C. sinensis sur l'épithélium des voies biliaires et les effets ultérieurs sur le microbiote biliaire restent inconnus. Méthodes : Des échantillons de voies biliaires félines ont été prélevés sur des chats non infectés et infectés par C. sinensis. Un examen histopathologique a été réalisé pour évaluer les modifications épithéliales, la fibrose, la mucine et la prolifération cellulaire à l'aide de la coloration à l'hématoxyline-éosine et de l'immunohistochimie. De plus, la composition du microbiote biliaire a été analysée par séquençage du gène de l'ARNr 16S. Des analyses statistiques ont été menées pour comparer la diversité microbienne et l'abondance relative entre les échantillons infectés et non infectés. Résultats : L'analyse histopathologique des voies biliaires félines infectées a révélé une hyperplasie épithéliale importante caractérisée par une prolifération cellulaire accrue. De plus, une fibrose péricanalaire et une fibrose du collagène ont été observées dans les échantillons infectés par rapport aux témoins non infectés. La richesse microbienne biliaire diminue avec la progression de la maladie par rapport aux témoins non infectés. L'abondance des streptocoques est positivement corrélée à la gravité de la maladie, dominant les communautés dans les échantillons avec cancer. L'analyse fonctionnelle prédictive suggère que C. sinensis pourrait favoriser les lésions des voies biliaires en augmentant les gènes microbiens pour le métabolisme des glucides, la réplication et la réparation. Conclusions : Cette étude fournit des informations complètes sur les effets pathologiques de l'infection à C. sinensis sur l'épithélium des voies biliaires félines et son influence sur la composition du microbiote biliaire. Ces nouvelles découvertes donnent un aperçu sur la pathogenèse de C. sinensis et pourraient éclairer le développement thérapeutique contre la clonorchiase humaine. Des recherches supplémentaires sont nécessaires pour élucider les mécanismes sous-jacents à l'origine de ces changements et leurs implications sur les interactions hôte-parasite.

Simultaneously blocking ANGPTL3 and IL-1ß for the treatment of atherosclerosis through lipid-lowering and anti-inflammation.

OBJECTIVE: Blood lipid levels play a critical role in the progression of atherosclerosis. However, even with adequate lipid reduction, significant residual cardiovascular risk remains. Therefore, it is necessary to seek novel therapeutic strategies for atherosclerosis that can not only lower lipid levels but also inhibit inflammation simultaneously. METHODS: The fusion protein FD03-IL-1Ra was designed by linking the Angiopoietin-like 3 (ANGPTL3) nanobody and human interleukin-1 receptor antagonist (IL-1Ra) sequences to a mutated human immunoglobulin gamma 1 (IgG1) Fc. This construct was transfected into HEK293 cells for expression. The purity and thermal stability of the fusion protein were assessed using SDS-PAGE, SEC-HPLC, and differential scanning calorimetry. Binding affinities of the fusion protein to ANGPTL3 and IL-1 receptor were measured using Biacore T200. The biological activity of the fusion protein was validated through in vitro experiments. The therapeutic efficacy of the fusion protein was evaluated in an ApoE-/- mouse model of atherosclerosis, including serum lipid level determination, histological analysis of aorta and aortic sinus sections, and detection of inflammatory and oxidative stress markers. ImageJ software was utilized for quantitative image analysis. Statistical analysis was performed using one-way ANOVA followed by Bonferroni post hoc test. RESULTS: The FD03-IL-1Ra fusion protein was successfully expressed, with no polymer formation detected, and it demonstrated good thermal and conformational stability. High affinity for both murine and human ANGPTL3 was exhibited by FD03-IL-1Ra, and it was able to antagonize hANGPTL3's inhibition of LPL activity. FD03-IL-1Ra also showed high affinity for both murine and human IL-1R, inhibiting IL-6 expression in A549 cells induced by IL-1ß stimulation, as well as suppressing IL-1ß-induced activity inhibition in A375.S2 cells. Our study revealed that the fusion protein effectively lowered serum lipid levels and alleviated inflammatory responses in mice. Furthermore, the fusion protein enhanced plaque stability by increasing collagen content within atherosclerotic plaques. CONCLUSIONS: These findings highlighted the potential of bifunctional interleukin-1 receptor antagonist and ANGPTL3 antibody fusion proteins for ameliorating the progression of atherosclerosis, presenting a promising novel therapeutic approach targeting both inflammation and lipid levels.

Anionic Solvation Transition at Low Temperatures for Reversible Anodes in Lithium-Oxygen Batteries.

Li-O2 batteries provide a novel technology for electric energy storage due to their high energy density. However, the strong solvent coordination with Li+ at low temperatures impacts their performance and triggers irreversible interfacial reactions on the Li anode. Herein, cyclopentyl methyl ether (CME) is incorporated in a dimethoxyethane (DME)-based electrolyte to realize an anionic solvation transition at low temperatures in Li-O2 batteries. CME featuring a single O coordination site substitutes highly solvating DME in the first solvation sheath, and it induces more anion coordination to Li+ across the room- and low-temperature ranges. The low residence time of CME (66 ps at 25 °C, 382 ps at -40 °C.) in the solvation structures leads to the fast exchange of coordinated CME molecules with Li+ in comparison with DME and facilitates Li+ desolvation at low temperatures. The simultaneously generated inorganic-rich solid electrolyte interphase promotes Li+ transport to improve Li deposition and suppress Li dendrite formation. These enable the Li-O2 battery to present a good cycling stability of 110 cycles with a fixed capacity of 1000 mA h g-1 at -40 °C. This work paves the way for designing novel electrolytes in low-temperature batteries.

Stabilizing Fe Single Atoms on Rutile-TiO2(110) Surface Via Atomic Substitution.

Stable anchoring of dispersed metal atoms through either surface adsorption or lattice substitution on support surfaces is a prerequisite for highly efficient catalytic performance. Atomic-level insights into these processes are necessary to understand the metal-support interactions. Here, we identify multiple Fe single-atom configurations on the rutile-TiO2(110) surface using scanning tunneling microscopy (STM) and density functional theory (DFT). Our results show that an Fe atom can either adsorb on a surface O site (configuration I) or stably substitute a surface lattice Ti atom (configuration II). A transformation from configuration I to configuration II can be induced by STM manipulation. Furthermore, the substitutional Fe atom can capture an additional Fe atom to form a dual Fe-Fe complex (configuration III). DFT calculations reveal that these Fe species contribute different states in either the bandgap or the conduction band. These atomistic insights pave the way for interrogating the integrated performance of nonprecious, TiO2-supported Fe single-atom catalysts.

Epitranscriptomic regulation of lipid oxidation and liver fibrosis via ENPP1 mRNA m6A modification.

BACKGROUND: Dysregulated lipid oxidation occurs in several pathological processes characterized by cell proliferation and migration. Nonetheless, the molecular mechanism of lipid oxidation is not well appreciated in liver fibrosis, which is accompanied by enhanced fibroblast proliferation and migration. METHODS: We investigated the causes and consequences of lipid oxidation in liver fibrosis using cultured cells, animal models, and clinical samples. RESULTS: Increased ecto-nucleotide pyrophosphatase/phosphodiesterase (ENPP1) expression caused increased lipid oxidation, resulting in the proliferation and migration of hepatic stellate cells (HSCs) that lead to liver fibrosis, whereas fibroblast-specific ENPP1 knockout reversing these results. Elevated ENPP1 and N6-methyladenosine (m6A) levels were associated with high expression of Wilms tumor 1 associated protein (WTAP). Mechanistically, WTAP-mediated m6A methylation of the 3'UTR of ENPP1 mRNA and induces its translation dependent of YTH domain family proteins 1 (YTHDF1). Additionally, ENPP1 could interact with hypoxia inducible lipid droplet associated (HILPDA) directly; overexpression of ENPP1 further recruits HILPDA-mediated lipid oxidation, thereby promotes HSCs proliferation and migration, while inhibition of ENPP1 expression produced the opposite effect. Clinically, increased expression of WTAP, YTHDF1, ENPP1, and HILPDA, and increased m6A mRNA content, enhanced lipid oxidation, and increased collagen deposition in human liver fibrosis tissues. CONCLUSIONS: We describe a novel mechanism in which WTAP catalyzes m6A methylation of ENPP1 in a YTHDF1-dependent manner to enhance lipid oxidation, promoting HSCs proliferation and migration and liver fibrosis.

Screening of herbal extracts binding with vascular endothelial growth factor by applying HerboChip platform.

BACKGROUND: Traditional Chinese medicine (TCM) has been hailed as a rich source of medicine, but many types of herbs and their functions still need to be rapidly discovered and elucidated. HerboChip, a target-based drug screening platform, is an array of different fractions deriving from herbal extracts. This study was designed to identify effective components from TCM that interact with vascular endothelial growth factor (VEGF) as a target using HerboChip. METHODS: Selected TCMs that are traditionally used as remedies for cancer prevention and wound healing were determined and extracted with 50% ethanol. Biotinylated-VEGF was hybridized with over 500 chips coated with different HPLC-separated fractions from TCM extracts and straptavidin-Cy5 was applied to identify plant extracts containing VEGF-binding fractions. Cytotoxicity of selected herbal extracts and their activities on VEGF-mediated angiogenic functions were evaluated. RESULTS: Over 500 chips were screened within a week, and ten positive hits were identified. The interaction of the identified herbal extracts with VEGF was confirmed in cultured endothelial cells. The identified herbs promoted or inhibited VEGF-mediated cell proliferation, migration and tube formation. Results from western blotting analysis demonstrated the identified herbal extracts significantly affected VEGF-triggered phosphorylations of eNOS, Akt and Erk. Five TCMs demonstrated potentiating activities on the VEGF response and five TCMs revealed suppressive activities. CONCLUSIONS: The current results demonstrated the applicability of the HerboChip platform and systematically elucidated the activity of selected TCMs on angiogenesis and its related signal transduction mechanisms.

Self-healing spiral phase contrast imaging.

Spiral phase contrast imaging alleviates the information load by extracting the geometric features of objects and is one of the most representative branches of instant imaging processing. The self-healing capacity of edge detectors can enhance their robustness to obstacles in practical applications. Here, a self-healing spiral phase contrast imaging scheme is proposed and experimentally demonstrated by a liquid crystal edge detector combining a spiral phase, an axicon phase, and a lens phase. The spiral phase is encoded into a liquid crystal by photopatterning. Self-healing contrast imaging is characterized by a series of edge images of both high-contrast amplitude-type and low-contrast phase-type objects. This work extends the self-healing capacity of these detectors to instant imaging processing and paves the way for optical applications with self-healing features.

Intra-marrow delivery of human interleukin-6-loaded biodegradable microspheres promotes growth of patient-derived multiple myeloma cells in mice.

Not available.

Natural variations in the Cis-elements of GhRPRS1 contributing to petal colour diversity in cotton.

The cotton genus comprises both diploid and allotetraploid species, and the diversity in petal colour within this genus offers valuable targets for studying orthologous gene function differentiation and evolution. However, the genetic basis for this diversity in petal colour remains largely unknown. The red petal colour primarily comes from C, G, K, and D genome species, and it is likely that the common ancestor of cotton had red petals. Here, by employing a clone mapping strategy, we mapped the red petal trait to a specific region on chromosome A07 in upland cotton. Genomic comparisons and phylogenetic analyses revealed that the red petal phenotype introgressed from G. bickii. Transcriptome analysis indicated that GhRPRS1, which encodes a glutathione S-transferase, was the causative gene for the red petal colour. Knocking out GhRPRS1 resulted in white petals and the absence of red spots, while overexpression of both genotypes of GhRPRS1 led to red petals. Further analysis suggested that GhRPRS1 played a role in transporting pelargonidin-3-O-glucoside and cyanidin-3-O-glucoside. Promoter activity analysis indicated that variations in the promoter, but not in the gene body of GhRPRS1, have led to different petal colours within the genus. Our findings provide new insights into orthologous gene evolution as well as new strategies for modifying promoters in cotton breeding.

Developed metabolomics approach reveals the non-volatile color-contributing metabolites during Keemun congou black tea processing.

While key aroma and taste compounds of Keemun Congou black teas (KCBT) form during aeration and thermal stages, it is still unknown whether these processing stages also produce non-volatile color-contributing metabolites. Through integrating metabolomics with correlation and ridge regression analyses, 190 metabolites were identified as marker compounds that reclassified 15 KCBT samples collected from five processing stages into four groups. Meanwhile, the results of quantification and heatmap analysis showed that the concentrations of theaflavins and theasinensins significantly increased, as catechin decreased, after rolling, while flavonoid aglycones and polyunsaturated fatty acids increased throughout drying. Regression analysis between marker compound levels and total color difference values (∆E) revealed that the major color contributors were 3,5-dicaffeoylquinic acid, glucosyl-dehydrodigallic acid, theacitrin A, kaempferol-O-robinobioside, and (-)-epigallocatechin, with regression coefficients (absolute value) exceeding 4 × 10-2. Overall, the present study confirmed that rolling and drying were the two vital stages responsible for the color formation of KCBT.

The application of the "perinephric fat wrapping" technique with oral mucosal graft for the management of ureter repair and reconstruction.

OBJECTIVE: The management of long-segment ureteral stenosis has posed a significant challenge for urologists. Ureteroplasty with oral mucosal graft has emerged as an effective approach for treating long-segment ureteral stenosis and defects. A key step in replacement repair surgery involves suturing the surrounding tissue with an adequate blood supply around the reconstructed ureter. The current study aims to evaluate the potential practical application of the "perinephric fat wrapping" technique in laparoscopic ureteroplasty with oral mucosal graft. METHODS: Between July 2018 and February 2023, 26 patients with ureteral stenosis underwent laparoscopic ureteroplasty with oral mucosal graft at the Second Affiliated Hospital of Anhui Medical University. We used traditional omental wrapping technique (OW group) or perinephric fat wrapping technique (PFW group) to enhance ureter repair. Perioperative and follow-up data for both groups were collected retrospectively and compared. RESULTS: There were 10 patients in OW group, including 4 males and 6 females, with BMI of 23.5±2.8 kg/m2 and stenosis length of 3.6±1.6 cm. There were 16 patients in the PFW group, including 10 males and 6 females, with a BMI of 26.1±3.3 kg/m2 and a median stenosis length of 2.3 cm (range, 1.2~6.0 cm). The operation of both groups was successfully completed, and no serious complications occurred during the operation. The mean operating time (OT) in the OW group was 200.6±41.9 min, the estimated amount of blood loss (EBL) was 25 ml (range, 10~30ml), and the median length of postoperative hospital stay (LHS) was 7.5 days (range 4.0~14.0 days). In the PFW group, the mean operating time (OT) was 211.9±38.3 min, the estimated blood loss (EBL) was 25 ml (range, 5~150ml), and the postoperative hospital stay (LHS) was 6.8±2.0 d. There was no significant difference between the two groups in the above indexes. Postoperative anal exhaust time was 1.0 d (range, 1.0~2.5d) in the PFW group and 1.9±0.5 d in the OW group, with significant difference between the two groups (P=0.009). The mean follow-up time was 36.8±15.9 months, and there was no significant difference between OW group and PFW group in the curative effect of operation. CONCLUSION: Perinephric fat wrapping technique not only avoids the potential effects of using omentum on abdominal organs, it is also as safe and effective as omentum wrapping technique in repairing and reconstructing the ureter using oral mucosal grafts.

Translation of HIV-1 unspliced RNA is regulated by 5' untranslated region structure.

HIV-1 must generate infectious virions to spread to new hosts and HIV-1 unspliced RNA (HIV-1 RNA) plays two central roles in this process. HIV-1 RNA serves as an mRNA that is translated to generate proteins essential for particle production and replication, and it is packaged into particles as the viral genome. HIV-1 uses several transcription start sites to generate multiple RNAs that differ by a few nucleotides at the 5' end, including those with one (1G) or three (3G) 5' guanosines. The virus relies on host machinery to translate its RNAs in a cap-dependent manner. Here, we demonstrate that the 5' context of HIV-1 RNA affects the efficiency of translation both in vitro and in cells. Although both RNAs are competent for translation, 3G RNA is translated more efficiently than 1G RNA. The 5' untranslated region (UTR) of 1G and 3G RNAs has previously been shown to fold into distinct structural ensembles. We show that HIV-1 mutants in which the 5' UTR of 1G and 3G RNAs fold into similar structures were translated at similar efficiencies. Thus, the host machinery translates two 99.9% identical HIV-1 RNAs with different efficiencies, and the translation efficiency is regulated by the 5' UTR structure.IMPORTANCEHIV-1 unspliced RNA contains all the viral genetic information and encodes virion structural proteins and enzymes. Thus, the unspliced RNA serves distinct roles as viral genome and translation template, both critical for viral replication. HIV-1 generates two major unspliced RNAs with a 2-nt difference at the 5' end (3G RNA and 1G RNA). The 1G transcript is known to be preferentially packaged over the 3G transcript. Here, we showed that 3G RNA is favorably translated over 1G RNA based on its 5' untranslated region (UTR) RNA structure. In HIV-1 mutants in which the two major transcripts have similar 5' UTR structures, 1G and 3G RNAs are translated similarly. Therefore, HIV-1 generates two 9-kb RNAs with a 2-nt difference, each serving a distinct role dictated by differential 5' UTR structures.

Decreased hospital-acquired respiratory infections among older inpatients during the COVID-19 pandemic: a retrospective observational study in a general hospital in China.

BACKGROUND: To mitigate hospital-acquired transmission of coronavirus disease 2019 (COVID-19), various prevention and control measures have been strictly implemented in medical institutions. These stringent measures can potentially reduce the incidence of hospital-acquired respiratory infections. This study aimed to assess if there were changes in the prevalence of hospital-acquired respiratory infections during a period of national attention focused on COVID-19 prevention. METHODS: A retrospective analysis of the clinical data from adult patients with hospital-acquired respiratory infections admitted between October and December 2019 and during the same period in 2020 was performed. All patients were referred from a general hospital in Beijing China and COVID-19 patients were not treated at the hospital. Hospital-acquired respiratory infections were diagnosed based on the criteria of the Centers for Disease Control and Prevention/National Healthcare Safety Network (CDC/NHSN). A comparison of the incidence and mortality rate of hospital-acquired respiratory infections between the two selected time periods was conducted. Additionally, multivariate logistics regression analysis was used to identify mortality-associated risk factors. RESULTS: This study included 2,211 patients from October to December 2019 (pre-COVID-19 pandemic) and 2,921 patients from October to December 2020 (during the COVID-19 pandemic). The incidence of hospital-acquired respiratory infections in 2019 and 2020 was 4.7% and 2.9%, respectively, with odds ratio (OR): 0.61, 95% confidence interval (CI): 0.46-0.81, and P = 0.001. In-hospital mortality of hospital-acquired respiratory infections in 2019 and 2020 was 30.5% and 38.4%, respectively, with OR: 1.42, 95%CI: 0.78-2.59, and P = 0.25. Multivariate logistics regression analysis revealed that a history of previous malignancy (OR: 2.50, 95%CI: 1.16-5.35, P = 0.02), was associated with in-hospital mortality. CONCLUSIONS: The incidence of hospital-acquired respiratory infections was significantly decreased following the implementation of various prevention and control measures during the COVID-19 pandemic. A history of previous malignancy was associated with higher in-hospital mortality in older inpatients with hospital-acquired respiratory infections.

Realizing Bright-Dark Dual-Field Multimode Optical Signals in Photochromic Apatite Phosphors for Security Identification.

Regulating defect distribution in inorganic phosphors is paramount for realizing multimode dual-field optical signals for high security level identification but remains an ongoing challenge. Here, we propose a strategy of equivalent anion doping and nonequivalent cation doping to successfully regulate the trap distribution and density in Ba5(PO4)3Cl:F-,Eu2+,Ce3+ (BPCF-AG) phosphors. Due to the coexistence of shallow and deep traps for different photon processes, the BPCF-AG exhibits simultaneous photochromism in a bright field and tetramode luminescence (photoluminescence, afterglow, 980 nm photostimulated luminescence, and 650/532 nm photostimulated afterglow) in a dark field. The trap roles responsible for versatile optical behaviors are investigated by thermoluminescence curves, and a reasonable mechanism is proposed. In addition, we design a series of demonstrations for security identification and information encryption based on the dual-field multimode optical signals of BPCF-AG to illustrate its potential application scenarios.

Targeting Rap1b signaling cascades with CDNF: Mitigating platelet activation, plasma oxylipins and reperfusion injury in stroke.

Cerebral reperfusion injury in stroke, stemming from interconnected thrombotic and inflammatory signatures, often involves platelet activation, aggregation and its interaction with various immune cells, contributing to microvascular dysfunction. However, the regulatory mechanisms behind this platelet activation and the resulting inflammation are not well understood, complicating the development of effective stroke therapies. Utilizing animal models and platelets from hemorrhagic stroke patients, our research demonstrates that human cerebral dopamine neurotrophic factor (CDNF) acts as an endogenous antagonist, mitigating platelet aggregation and associated neuroinflammation. CDNF moderates mitochondrial membrane potential, reactive oxygen species production, and intracellular calcium in activated platelets by interfering with GTP binding to Rap1b, thereby reducing Rap1b activation and downregulating the Rap1b-MAPK-PLA2 signaling pathway, which decreases release of the pro-inflammatory mediator thromboxane A2. In addition, CDNF reduces the inflammatory response in BV2 microglial cells co-cultured with activated platelets. Consistent with ex vivo findings, subcutaneous administration of CDNF in a rat model of ischemic stroke significantly reduces platelet activation, aggregation, lipid mediator production, infarct volume, and neurological deficits. In summary, our study highlights CDNF as a promising therapeutic target for mitigating platelet-induced inflammation and enhancing recovery in stroke. Harnessing the CDNF pathway may offer a novel therapeutic strategy for stroke intervention.

Macrophage membrane-camouflaged biomimetic nanoparticles for rheumatoid arthritis treatment via modulating macrophage polarization.

Rheumatoid arthritis (RA) is a debilitating autoimmune disease characterized by chronic joint inflammation and cartilage damage. Current therapeutic strategies often result in side effects, necessitating the development of targeted and safer treatment options. This study introduces a novel nanotherapeutic system, 2-APB@DGP-MM, which utilizes macrophage membrane (MM)-encapsulated nanoparticles (NPs) for the targeted delivery of 2-Aminoethyl diphenylborinate (2-APB) to inflamed joints more effectively. The NPs are designed with a matrix metalloproteinase (MMP)-cleavable peptide, allowing for MMP-responsive drug release within RA microenvironment. Comprehensive in vitro and in vivo assays confirmed the successful synthesis and loading of 2-APB into the DSPE-GPLGVRGC-PEG (DGP) NPs, as well as their ability to repolarize macrophages from a pro-inflammatory M1 to an anti-inflammatory M2 phenotype. The NPs demonstrated high biocompatibility, low cytotoxicity, and enhanced cellular uptake. In a collagen-induced arthritis (CIA) mouse model, intra-articular injection of 2-APB@DGP-MM significantly reduced synovial inflammation and cartilage destruction. Histological analysis corroborated these findings, demonstrating marked improvements in joint structure and delayed disease progression. Above all, the 2-APB@DGP-MM nanotherapeutic system offers a promising and safe approach for RA treatment by modulating macrophage polarization and delivering effective agents to inflamed joints.

The association between occupational stress, sleep quality and premenstrual syndrome among clinical nurses.

OBJECTIVE: Premenstrual Syndrome is also known as premenstrual tension syndrome because of the pronounced premenstrual mental and emotional anomalies. This study focuses on the association between occupational stress, sleep quality and premenstrual syndrome in clinical nurses and the mediating role of sleep quality. METHODS: A cross-sectional study was conducted to measure occupational stress, sleep quality and premenstrual syndrome in 415 clinical nurses using the Chinese Nurses Stressor Scale, the Pittsburgh Sleep Quality Index Scale, and the Premenstrual Syndrome Scale. SPSS was used to explore the relationship between the variables, and AMOS was used to explore the mediating role between the variables. RESULTS: Nurses' occupational stress positively predicted PMS (ß = 0.176, p < 0.001), and the regression coefficients for sleep quality were significantly different for both paths of nurses' occupational stress (ß = 0.665, p < 0.001) and PMS (ß = 0.261, p < 0.001). The mediation effect accounts for 49.57% of the total effect. CONCLUSION: This study revealed a notably high incidence of PMS among clinical nurses in China, with occupational stress and sleep quality significantly correlated with PMS. Sleep quality played an intermediary role between occupational stress and PMS. Consequently, managers should prioritize addressing occupational stress, mitigating PMS symptoms, enhancing nurses' health and nursing quality, and preventing nursing risks through mental health support and improving sleep quality.

A Randomized, Double-Blind, Parallel-Group Phase I Study Comparing the Pharmacokinetics, Safety, and Immunogenicity of CMAB015, a Candidate Secukinumab Biosimilar, with Its Reference Product Cosentyx® in Healthy Chinese Male Subjects.

Purpose: Secukinumab, a monoclonal antibody targeting interleukin (IL)-17A, is approved for the treatment of psoriasis, psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, enthesitis-related arthritis, and hidradenitis suppurativa. This study compared the pharmacokinetics (PK), safety, and immunogenicity of CMAB015, a candidate secukinumab biosimilar, with the reference product secukinumab (Cosentyx®) in healthy Chinese male subjects. Patients and methods: This double-blind, parallel-group study randomized healthy Chinese male subjects (N=130) to receive either a single dose of 150 mg CMAB015 or secukinumab subcutaneously. Primary study endpoints were PK parameters such as the maximum concentration (Cmax) and area under the curve from zero to infinity (AUC0-inf), while safety and immunogenicity were secondary endpoints. Results: The 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) of Cmax and AUC0-inf for CMAB015 to secukinumab were all within the bioequivalence limits (80.00-125.00%). Other PK parameters were comparable between the groups. The safety profile of CMAB015 was similar to that of secukinumab, with no serious adverse events related to treatment. The incidence of TEAEs was slightly higher in the CMAB015 group, but these events were mild to moderate in severity and did not lead to any withdrawals from the study. Immunogenicity analysis revealed low rates of anti-drug antibody (ADA) positivity, with similar rates between CMAB015 and secukinumab. Conclusion: This study demonstrated equivalent PK, comparable safety, and immunogenicity of CMAB015 to secukinumab in healthy Chinese male subjects. These findings support further clinical evaluation of CMAB015 as a secukinumab biosimilar. Trial Registration: The trial was registered on Clinicaltrials.gov (Identifier No. NCT05734482) and Chinadrugtrials.org.cn (Identifier No. CTR20230105).