Methacrylated hyaluronic acid/laponite photosensitive, sustained-release hydrogel loaded with bilobalide for enhancing random flap survival through mitigation of endoplasmic reticulum stress.

Random flaps are extensively utilized in plastic surgery due to their flexibility compared to traditional axial vascular system arrangements and their resemblance to injured skin in color, thickness, and texture. Despite these advantages, they are susceptible to ischemia-reperfusion injuries and subsequent necrosis post-transplantation. Bilobalide (BB), a sesquiterpene compound derived from Ginkgo biloba, exhibits notable antioxidant and anti-inflammatory properties and is commonly used to treat ischemiareperfusion injuries. However, its short half-life restricts its sustained efficacy in random flaps. In this study, we synthesized a multi-crosslinked, photosensitive methacryloyl hyaluronic acid(HAMA)/laponite(Lap)/bilobalide (BB) hydrogel. This dualcrosslinked hydrogel demonstrates superior mechanical properties and biocompatibility while providing a stable release of bilobalide. In vitro experiments showed that it significantly reduces edema, promotes angiogenesis, and enhances the survival of random flaps. Further network pharmacology analysis and recovery experiments suggested that the hydrogel's beneficial effects are mediated by the regulation of endoplasmic reticulum stress and specifically identified the regulation of the PERK/TXNIP/NLRP3 signaling pathway as crucial to its anti-inflammatory effects. Therefore, this HAMA/Lap/BB hydrogel promotes the survival of random flaps in rats by alleviating endoplasmic reticulum stress, providing a novel intervention strategy for the treatment of random flaps injuries.

Vinpocetine protects against osteoarthritis by inhibiting ferroptosis and extracellular matrix degradation via activation of the Nrf2/GPX4 pathway.

BACKGROUND: Osteoarthritis (OA) is a progressive joint condition marked by the slow degradation of articular cartilage. Vinpocetine (Vin), a synthetic derivative of vincamine derived from the vinca plant, exhibits anti-inflammatory and antioxidant properties. Nevertheless, the specific role and mechanism of Vin in the treatment of OA remain largely unexplored. OBJECTIVES: The study is designed to uncover the impacts of Vin on tert­butyl hydroperoxide (TBHP)-induced ferroptosis and to explore its potential role and underlying mechanisms in the treatment of OA. Concurrently, we established an OA mouse model through medial meniscal instability surgery to assess the therapeutic effects of Vin in vivo. METHODS: Through network pharmacology analysis, we have identified the key targets and potential pathways of Vin. To simulate an oxidative stress-induced OA environment in vitro, we induced chondrocyte injury using TBHP. We tested how Vin affects chondrocytes under TBHP induction by DHE and DCFH-DA probes, BODIPY-C11 and FerroOrange staining, mitochondrial function assessment, Western blotting, co-immunoprecipitation, and immunofluorescence techniques. Simultaneously, we established an OA mouse model through medial meniscal instability surgery to assess the in vivo therapeutic effects of Vin. In this model, we used X-ray and micro-CT imaging, SO staining, TB staining, H&E staining, and immunohistochemistry to analyze the role of Vin in detail. RESULTS: This study demonstrated that Vin effectively suppressed TBHP-induced ferroptosis and extracellular matrix (ECM) degradation and significantly lessened mitochondrial damage associated with ferroptosis. In the OA mouse model, Vin improved cartilage degeneration, subchondral remodeling, synovitis, and ECM degradation. Vin worked by activating the Nrf2/GPX4 pathway and inhibiting the Keap1-Nrf2 interaction. This study focused on the function of ferroptosis in OA and its influence on chondrocyte damage and disease progression, offering novel perspectives on potential treatments. CONCLUSION: Vin activated the Nrf2/GPX4 pathway, thereby slowing OA progression, inhibiting ferroptosis, and preventing ECM degradation.

Orientin promotes diabetic wounds healing by suppressing ferroptosis via activation of the Nrf2/GPX4 pathway.

Diabetic patients often experience delayed wound healing due to impaired functioning of human umbilical vein endothelial cells (HUVECs) under high glucose (HG) conditions. This is because HG conditions trigger uncontrolled lipid peroxidation, leading to iron-dependent ferroptosis, which is caused by glucolipotoxicity. However, natural flavonoid compound Orientin (Ori) possesses anti-inflammatory bioactive properties and is a promising treatment for a range of diseases. The current study aimed to investigate the function and mechanism of Ori in HG-mediated ferroptosis. A diabetic wound model was established in mice by intraperitoneal injection of streptozotocin (STZ), and HUVECs were cultured under HG to create an in vitro diabetic environment. The results demonstrated that Ori inhibited HG-mediated ferroptosis, reducing levels of malondialdehyde (MDA), lipid peroxidation, and mitochondrial reactive oxygen species (mtROS), while increasing decreased levels of malondialdehyde, lipid peroxidation, and mitochondrial reactive oxygen species, as well as increased levels of glutathione (GSH). Ori treatment also improved the wound expression of glutathione peroxidase 4 (GPX4) and angiogenesis markers, reversing the delayed wound healing caused by diabetes mellitus (DM). Additional investigations into the mechanism revealed that Ori may stimulate the nuclear factor-erythroid 2-related factor 2 (Nrf2)/GPX4 signaling pathway. Silencing Nrf2 in HG-cultured HUVECs negated the beneficial impact mediated by Ori. By stimulating the Nrf2/GPX4 signaling pathway, Ori may expedite diabetic wound healing by decreasing ferroptosis.

OTULIN's influence on neuroinflammation and pain modulation in trigeminal neuralgia.

INTRODUCTION: Trigeminal neuralgia (TN), marked by chronic pain from neural damage, is closely associated with inflammation. The role of OTULIN, a key regulator in inflammation and autophagy, is not fully understood in TN. The regulatory mechanism of OTULIN, a key protein involved in modulating inflammatory responses and autophagy processes, remains incompletely elucidated, particularly in the context of TN and neuroinflammation. METHODS: An infraorbital nerve ligation-induced rat model of TN was used. OTULIN's expression was modulated using adenovirus vectors and short hairpin RNA. The impact on pain and inflammatory responses was assessed via quantitative real-time polymerase chain reaction, western blot, immunofluorescence, and transcriptomic analysis. RESULTS: Enhanced OTULIN expression significantly increased head withdrawal thresholds and reduced pain sensitivity and neuroinflammatory markers in the model. Conversely, silencing OTULIN exacerbated pain and inflammation. Transcriptomic data revealed OTULINs influence on both inflammatory and autophagy pathways, specifically in suppressing NLR family pyrin domain containing 3 (NLRP3) inflammasome and promoting autophagy. In vitro experiments demonstrated OTULIN's inhibition of inflammatory markers in microglia and neurons. CONCLUSION: OTULIN is crucial in modulating TN, reducing neuropathic pain and neuroinflammation by activating the autophagy pathway and inhibiting the NLRP3 inflammasome.

Delay the progression of glucocorticoid-induced osteoporosis: Fraxin targets ferroptosis via the Nrf2/GPX4 pathway.

Glucocorticoid-induced osteoporosis (GIOP) commonly accelerates bone loss, increasing the risk of fractures and osteonecrosis more significantly than traditional menopausal osteoporosis. The extracellular environment influenced by glucocorticoids heightens fracture and osteonecrosis risks. Fraxin (Fra), a key component of the traditional Chinese herbal remedy Cortex Fraxini, is known for its wide-ranging pharmacological effects, but its impact on GIOP remains unexplored. This investigation aims to delineate the effects and underlying mechanisms of Fra in combating dexamethasone (Dex)-induced ferroptosis and GIOP. We established a mouse model of GIOP via intraperitoneal injections of Dex and cultured osteoblasts with Dex treatment for in vitro analysis. We evaluated the impact of Fra on Dex-treated osteoblasts through assays such as C11-BODIPY and FerroOrange staining, mitochondrial functionality tests, and protein expression analyses via Western blot and immunofluorescence. The influence of Fra on bone microarchitecture of GIOP in mice was assessed using microcomputerized tomography, hematoxylin and eosin staining, double-labeling with Calcein-Alizarin Red S, and immunohistochemistry at imaging and histological levels. Based on our data, Fra prevented Dex-induced ferroptosis and bone loss. In vitro, glutathione levels increased and malondialdehyde, lipid peroxidation, and mitochondrial reactive oxygen species decreased. Fra treatment also increases nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4), and COL1A1 expression and promotes bone formation. To delve deeper into the mechanism, the findings revealed that Fra triggered the activation of Nrf2/GPX4 signaling. Moreover, the use of siRNA-Nrf2 blocked the beneficial effect of Fra in osteoblasts cultivated with Dex. Fra effectively combats GIOP by activating the Nrf2/GPX4 signaling pathway to inhibit ferroptosis.

[Identification and Derivation of Emerging Contaminants in the Roof Rainwater Confluence].

To identify emerging contaminants （ECs） in rainwater is a topic that has gradually received widespread attention. Rainwater resources, specifically urban roofs, play a crucial role in utilizing rainwater efficiently by understanding the occurrence and migration characteristics of pollutants in precipitation. This study selected a typical roof and studied the differences in rainwater quality and pollution occurrence at different collection stages during six rainfall events from March to May in 2023. Principal component analysis （PCA） and correlation analysis were used to explore the distribution, migration, and transformation of ECs in the collection process of roof rainwater. The findings revealed the presence of 44/54 ECs in wet deposition, dry and wet deposition, and roof runoff processes, with a total concentration range of 63.0 to 432.4 ng·L-1 and an average concentration of 166.8 ng·L-1. Notably, bisphenol A （BPA） exhibited the highest concentration, ranging from 14.7 to 265.6 ng·L-1, with an average concentration of 62.5 ng·L-1, followed by ofloxacin （OFX） and ethylhexyl methoxycinnamate （EHMC）, with detected concentrations up to 45.5 ng·L-1 and 44.8 ng·L-1. Dissolved organic matter （DOM）, nitrogen pollutants, and particulate matter were important factors affecting the occurrence characteristics of ECs, with a mantel correlation coefficient of up to 0.98 （P<0.01）. Based on the analysis of different rainfall events and collection stages, variations were observed in the accumulation pathways and contribution ratios of different pollutants. The wet deposition exhibited the highest content of ECs in the initial stage, whereas the dry and wet deposition and roof runoff processes displayed higher ECs content in the later stages. Additionally, the average ECs contribution rates of dry and wet deposition to roof runoff were 21.48% and 78.52%, respectively. Due to the influence of roof material and surface roughness retention performance, over 30% of ECs, including pharmaceuticals and personal care products （PPCPs）, endocrine-disrupting compounds （EDCs）, and pesticides, were deposited on the roof during the runoff collection. The results of this research can provide the theoretical foundation and technical support for the identification and control of ECs in urban roof runoff and for the safe storage of rainwater.

Effect of Customized Nutritious Breakfast and Nutrition Education on Nutritional Status of Preschool Children in Economically Underdeveloped Multi-Ethnic Areas: A Cluster Randomized Clinical Trial in Linxia, China.

The nutritional status of preschool children in economically underdeveloped multi-ethnic areas is a global concern. This study aimed to examine the effect of a 2.2-year cluster randomized clinical trial that provided customized nutritious breakfast and nutrition education to preschool children in Linxia County, China. A total of 578 children aged 3 to 6 years were enrolled. After the intervention, the incidence of undernourishment was significantly lower in the intervention group compared to the control group (8.73% vs. 9.92%, OR = 0.01 [95%CI 0.00, 0.39], p = 0.014). Additionally, children with non-Muslim dietary habits had a lower incidence of undernourishment compared to those with Muslim dietary habits (OR = 0.05 [95%CI 0.00, 0.88]; p = 0.010). The intervention group also had a lower prevalence rate of wasting (OR = 0.02 [95%CI 0.00, 0.40]; p = 0.011) and a higher mean BMI-for-age Z-score (ß = 1.05 [95%CI 0.32, 1.77]; p = 0.005) compared to the control group. These findings suggest that providing nutritious breakfast and nutrition education is an effective strategy to improve the nutrition and health of preschool children, particularly in economically disadvantaged regions and among children with Muslim dietary habits.

MXenes with ordered triatomic-layer borate polyanion terminations.

Surface terminations profoundly influence the intrinsic properties of MXenes, but existing terminations are limited to monoatomic layers or simple groups, showing disordered arrangements and inferior stability. Here we present the synthesis of MXenes with triatomic-layer borate polyanion terminations (OBO terminations) through a flux-assisted eutectic molten etching approach. During the synthesis, Lewis acidic salts act as the etching agent to obtain the MXene backbone, while borax generates BO2- species, which cap the MXene surface with an O-B-O configuration. In contrast to conventional chlorine/oxygen-terminated Nb2C with localized charge transport, OBO-terminated Nb2C features band transport described by the Drude model, exhibiting a 15-fold increase in electrical conductivity and a 10-fold improvement in charge mobility at the d.c. limit. This transition is attributed to surface ordering that effectively mitigates charge carrier backscattering and trapping. Additionally, OBO terminations provide Ti3C2 MXene with substantially enriched Li+-hosting sites and thereby a large charge-storage capacity of 420 mAh g-1. Our findings illustrate the potential of intricate termination configurations in MXenes and their applications for (opto)electronics and energy storage.

Exploring the role of CDCA4 in liver hepatocellular carcinoma using bioinformatics analysis and experiments.

Liver hepatocellular carcinoma (LIHC) encompasses diverse therapeutic approaches, among which targeted therapy has gained significant prominence in recent years. The identification of numerous targets and the increasing clinical application of targeted drugs have greatly improved LIHC treatment. However, the precise role of CDCA4 (Cell Division Cycle Associated 4), as well as its underlying mechanisms and prognostic implications in LIHC, remains unclear. CDCA4 expression levels in LIHC were analyzed using multiple databases including the cancer genome atlas (TCGA), gene expression profiling interactive analysis (GEPIA), and ULCAN, as well as the datasets E_TABM_36, GSE144269, GSE14520, and GSE54236. The prognostic value of CDCA4 was then evaluated. Subsequently, the association between CDCA4 and immune cells was investigated. Enrichment analysis (GSEA) was utilized to investigate the functional roles and pathways linked to CDCA4. Additionally, the methylation patterns and drug sensitivity of CDCA4 were examined. A predictive model incorporating immune genes related to CDCA4 was developed. The TISCH dataset was used to investigate the single-cell expression patterns of CDCA4. Finally, validation of CDCA4 expression levels was conducted through RT-PCR, Western blotting, and immunohistochemistry. CDCA4 exhibited significant overexpression in LIHC and demonstrated significant correlations with clinical features. High expression of CDCA4 is associated with a poorer prognosis. Analysis of immune infiltration and enrichment revealed its association with the immune microenvironment. Furthermore, its expression is correlated with methylation and mutation patterns. CDCA4 is associated with 19 drugs. Prognostic models utilizing CDCA4 demonstrate favorable effectiveness. T cell subtypes were found to be associated with CDCA4 through single-cell analysis. The conclusive experiment provided evidence of significant upregulation of CDCA4 in LIHC. The high expression of CDCA4 in LIHC is associated with prognostic significance and is highly expressed in T cell subtypes, providing a new therapeutic target and potential therapeutic strategy for LIHC.

Genome-Wide CRISPR Screen Identifies an NF2-Adherens Junction Mechanistic Dependency for Cardiac Lineage.

BACKGROUND: Cardiomyocyte differentiation involves a stepwise clearance of repressors and fate-restricting regulators through the modulation of BMP (bone morphogenic protein)/Wnt-signaling pathways. However, the mechanisms and how regulatory roadblocks are removed with specific developmental signaling pathways remain unclear. METHODS: We conducted a genome-wide CRISPR screen to uncover essential regulators of cardiomyocyte specification in human embryonic stem cells using a myosin heavy chain 6 (MYH6)-GFP (green fluorescence protein) reporter system. After an independent secondary single guide ribonucleic acid validation of 25 candidates, we identified NF2 (neurofibromin 2), a moesin-ezrin-radixin like (MERLIN) tumor suppressor, as an upstream driver of early cardiomyocyte lineage specification. Independent monoclonal NF2 knockouts were generated using CRISPR-Cas9, and cell states were inferred through bulk RNA sequencing and protein expression analysis across differentiation time points. Terminal lineage differentiation was assessed by using an in vitro 2-dimensional-micropatterned gastruloid model, trilineage differentiation, and cardiomyocyte differentiation. Protein interaction and post-translation modification of NF2 with its interacting partners were assessed using site-directed mutagenesis, coimmunoprecipitation, and proximity ligation assays. RESULTS: Transcriptional regulation and trajectory inference from NF2-null cells reveal the loss of cardiomyocyte identity and the acquisition of nonmesodermal identity. Sustained elevation of early mesoderm lineage repressor SOX2 and upregulation of late anticardiac regulators CDX2 and MSX1 in NF2 knockout cells reflect a necessary role for NF2 in removing regulatory roadblocks. Furthermore, we found that NF2 and AMOT (angiomotin) cooperatively bind to YAP (yes-associated protein) during mesendoderm formation, thereby preventing YAP activation, independent of canonical MST (mammalian sterile 20-like serine-threonine protein kinase)-LATS (large tumor suppressor serine-threonine protein kinase) signaling. Mechanistically, cardiomyocyte lineage identity was rescued by wild-type and NF2 serine-518 phosphomutants, but not NF2 FERM (ezrin-radixin-meosin homology protein) domain blue-box mutants, demonstrating that the critical FERM domain-dependent formation of the AMOT-NF2-YAP scaffold complex at the adherens junction is required for early cardiomyocyte lineage differentiation. CONCLUSIONS: These results provide mechanistic insight into the essential role of NF2 during early epithelial-mesenchymal transition by sequestering the repressive effect of YAP and relieving regulatory roadblocks en route to cardiomyocytes.

Time of exercise differentially impacts bone growth in mice.

Although physical training has been shown to improve bone mass, the time of day to exercise for optimal bone growth remains uncertain. Here we show that engaging in physical activity during the early active phase, as opposed to the subsequent active or rest phase, results in a more substantial increase in bone length of male and female mice. Transcriptomic and metabolomic methodologies identify that exercise during the early active phase significantly upregulates genes associated with bone development and metabolism. Notably, oxidative phosphorylation-related genes show a rhythmic expression in the chondrification centre, with a peak at the early active phase, when more rhythmic genes in bone metabolism are expressed and bone growth is synergistically promoted by affecting oxidative phosphorylation, which is confirmed by subsequent pharmacological investigations. Finally, we construct a signalling network to predict the impact of exercise on bone growth. Collectively, our research sheds light on the intricacies of human exercise physiology, offering valuable implications for interventions.

Sipeimine ameliorates osteoarthritis progression by suppression of NLRP3 inflammasome-mediated pyroptosis through inhibition of PI3K/AKT/NF-κB pathway: An in vitro and in vivo study.

Background: Osteoarthritis (OA) is a chronic and degenerative condition that persists and progresses over time. Sipeimine (Sip), a steroidal alkaloid derived from Fritillariae Cirrhosae Bulbus, has attracted considerable attention due to its exceptional anti-inflammatory, analgesic, antioxidant, and anti-cancer characteristics. However, Sip's effects on OA and its mechanism still need further research. Methods: This study utilized network pharmacology to identify initial targets for Sip. Functional associations of Sip in OA were clarified through Gene Ontology (GO) enrichment analysis, bioinformatically analyzing a list of targets. Subsequently, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis assessed pathways linked to Sip's therapeutic efficacy in OA. Molecular docking techniques explored Sip's binding affinity with key targets. In vitro experiments assessed Sip's impact on lipopolysaccharide (LPS)-induced pro-inflammatory factors and its protective effects on collagen-II and aggrecan degradation within the extracellular matrix (ECM). Western blotting and fluorescence analyses were conducted to determine Sip-mediated signaling pathways. Moreover, in vivo experiments using a mouse OA model validated Sip's therapeutic efficacy. Results: The results from network pharmacology revealed a total of 57 candidate targets for Sip in OA treatment. GO enrichment analysis demonstrated a robust correlation between Sip and inflammatory response, response to LPS and NF-κB-inducing kinase activity in OA. KEGG enrichment analysis highlighted the significance of NF-κB and PI3K-AKT pathways in Sip's therapeutic potential for OA. Furthermore, molecular docking results demonstrated Sip's robust binding affinity with p65 and PI3K. In vitro experiments demonstrated Sip's effectively suppressed the expression of pro-inflammatory factors induced by LPS, such as COX-2, iNOS, IL-1ß, and IL-18. Besides, Sip counteracted the degradation of collagen-II and aggrecan within the ECM and the expression of MMP-13 and ADAMTS-5 mediated by LPS. The safeguarding effects of Sip were ascribed to its inhibition of PI3K/AKT/NF-κB pathway and NLRP3 inflammasome mediated pyroptosis. Additionally, in vivo experiments revealed that Sip could alleviate the subchondral remodeling, cartilage degeneration, synovitis as well as ECM degradation a mouse model of OA. Conclusion: Sip exhibited potential in attenuating OA progression by suppressing the PI3K/AKT/NF-κB pathway, consequently inhibiting the activation of NLRP3 inflammasome and pyroptosis. The translational potential statement: The translational potential of this articleThis study provides a biological rationale for the use of Sip as a potential candidate for OA treatment, provide a new concept for the cartilage targeted application of natural compounds.

Cucurbitacin B attenuates osteoarthritis development by inhibiting NLRP3 inflammasome activation and pyroptosis through activating Nrf2/HO-1 pathway.

Osteoarthritis (OA) is a complicated joint disorder characterized by inflammation that causes joint destruction. Cucurbitacin B (CuB) is a naturally occurring triterpenoid compound derived from plants in the Cucurbitaceae family. The aim of this study is to investigate the potential role and mechanisms of CuB in a mouse model of OA. This study identified the key targets and potential pathways of CuB through network pharmacology analysis. In vivo and in vitro studies confirmed the potential mechanisms of CuB in OA. Through network pharmacology, 54 potential targets for CuB in treating OA were identified. The therapeutic potential of CuB is associated with the nod-like receptor pyrin domain 3 (NLRP3) inflammasome and pyroptosis. Molecular docking results indicate a strong binding affinity of CuB to nuclear factor erythroid 2-related factor 2 (Nrf2) and p65. In vitro experiments demonstrate that CuB effectively inhibits the expression of pro-inflammatory factors induced by interleukin-1ß (IL-1ß), including cyclooxygenase-2, inducible nitric oxide synthase, IL-1ß, and IL-18. CuB inhibits the degradation of type II collagen and aggrecan in the extracellular matrix (ECM), as well as the expression of matrix metalloproteinase-13 and a disintegrin and metalloproteinase with thrombospondin motifs-5. CuB protects cells by activating the Nrf2/hemeoxygenase-1 (HO-1) pathway and inhibiting nuclear factor-κB (NF-κB)/NLRP3 inflammasome-mediated pyroptosis. Moreover, in vivo experiments show that CuB can slow down cartilage degradation in an OA mouse model. CuB effectively prevents the progression of OA by inhibiting inflammation in chondrocytes and ECM degradation. This action is further mediated through the activation of the Nrf2/HO-1 pathway to inhibit NF-κB/NLRP3 inflammasome activation. Thus, CuB is a potential therapeutic agent for OA.

The Primary Afferents of Trigeminal Autonomic Reflex May not be Nociceptive: A Case Report.

Autonomic symptoms have been long noticed coming along with pain in the head, e.g. Trigeminal Neuralgia, trigeminal autonomic cephalalgias. The symptoms show up during pain attacks, so they are assumed to be activated by the nociceptive afferents of the trigeminal nerve. Here, we present a case with hypersalivation as the complication after percutaneous balloon compression for trigeminal neuralgia, although the patient was pain-free after the treatment. A 71-year-old female with excessive salivation on the affected side after percutaneous balloon compression is described. The patient underwent microvascular decompression several years ago, and both the microvascular decompression and the preoperative imaging examination confirmed that there was no offending vessel at the root entry zone of the trigeminal nerve. After the percutaneous balloon compression, the patient was free of pain, but the autonomic symptoms (hypersalivation) still showed up. The autonomic symptoms which usually came along with pain presented solely as post-percutaneous balloon compression complication in the case. Contrary to popular belief, for the patient who was pain-free after percutaneous balloon compression, the transiently overactivated nerve fibers that led to hypersalivation were not nociceptive afferents of the trigeminal nerve.

The relationship between marital status and cognitive impairment in Chinese older adults: the multiple mediating effects of social support and depression.

BACKGROUND: Marital status is a potentially essential factor for cognitive impairment. Relevant research examining the potential pathways through which the marital status of spouseless older people is associated with cognitive impairment needs to be more adequate. Therefore, this study aims to investigate the serial mediating effects of various forms of social support and depression between marital status and cognitive impairment in older Chinese people. METHODS: This study involved a secondary analysis of data from the 2014-2018 wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS), with a total of 2,647 Chinese older adults and 53.6% being males. Mediation analysis using the SPSS process macro was conducted. RESULTS: The results indicated that marital status was significantly predictive of cognitive impairment among older people, and those with a spouse exhibited higher cognitive functioning. Informal social support and depression were found to play partial mediating roles in the association between marital status and cognitive impairment. The findings also revealed that marital status was unrelated to formal social support, and no association between formal social support and cognitive impairment was found. CONCLUSIONS: The study findings highlight the need for social service providers to design programs for promoting connections associated with informal support to reduce their risk of depression and cognitive impairment and for policymakers to develop effective formal social support systems for older people without spouses. This study indicated that older people could regain the benefits of marriage to lower the risk of depression and improve their mental health.

Corrigendum: Clinical value of serum complement component 1q levels in the prognostic analysis of aneurysmal subarachnoid hemorrhage: a prospective cohort study.

[This corrects the article DOI: 10.3389/fneur.2024.1341731.].

Corynoline Suppresses Osteoclastogenesis and Attenuates ROS Activities by Regulating NF-κB/MAPKs and Nrf2 Signaling Pathways.

Declining estrogen production in postmenopausal females causes osteoporosis in which the resorption of bone exceeds the increase in bone formation. Although clinical drugs are currently available for the treatment of osteoporosis, sustained medication use is accompanied by serious side effects. Corydalis bungeana Herba, a famous traditional Chinese herb listed in the Chinese Pharmacopoeia Commission, constitutes various traditional Chinese Medicine prescriptions, which date back to thousands of years. One of the primary active components of C. bungeana Turcz. is Corynoline (Cor), a plant isoquinoline alkaloid derived from the Corydalis species, which possesses bone metabolism disease therapeutic potential. The study aimed at exploring the effects as well as mechanisms of Cor on osteoclast formation and bone resorption. TRAcP staining, F-actin belt formation, and pit formation were employed for assessing the osteoclast function. Western blot, qPCR, network pharmacology, and docking analyses were used for analyzing the expression of osteoclast-associated genes and related signaling pathways. The study focused on investigating how Cor affected OVX-induced trabecular bone loss by using a mouse model. Cor could weaken osteoclast formation and function by affecting the biological receptor activators of NF-κB and its ligand at various concentrations. Mechanistically, Cor inhibited the NF-κB activation, and the MAPKs pathway stimulated by RANKL. Besides, Cor enhanced the protein stability of the Nrf2, which effectively abolished the RANKL-stimulated ROS generation. According to an OVX mouse model, Cor functions in restoring bone mass, improving microarchitecture, and reducing the ROS levels in the distal femurs, which corroborated with its in vitro antiosteoclastogenic effect. The present study indicates that Cor may restrain osteoclast formation and bone loss by modulating NF-κB/MAPKs and Nrf2 signaling pathways. Cor was shown to be a potential drug candidate that can be utilized for the treatment of osteoporosis.

Comparison of young femoral neck fractures treated by femoral neck system, multiple cancellous screws and dynamic hip screws: a retrospectively comparison study.

BACKGROUND: Implant choice for the fixation of femoral neck fracture is one of the most important management controversies. This study aims to evaluate and compare the short-term outcomes associated with the use of the Femoral Neck System (FNS), Multiple Cancellous Screws (MCS), and Dynamic Hip Screws (DHS) in treating femoral neck fractures in a young patient population. METHODS: From June 2018 to June 2021, a total of 120 surgeries for a primary femoral neck fracture were retrospectively analyzed. This review encompassed demographic details of the patients and the mechanisms behind the injuries. Key surgical parameters such as operation duration, intraoperative blood loss, fluoroscopy duration, and hospital stay were meticulously documented. The employed surgical technique was described. All patients were followed up at 6 weeks, 3 months, 6 months, and 12 months postoperatively. Avascular necrosis of the femoral head (AVN), nonunion, malreduction, implant failure or other complications were noted. The functional status at the last follow-up was assessed using the Harris functional scoring criteria. RESULTS: There were 90 males and 30 females, with a mean age of 40.4 years. As to patient characteristics, there were no significant differences between the three groups. DHS group showed longer operation time(52.15 ± 4.80 min), more blood loss(59.05 ± 5.87 ml) and longer time of hospitalization(7.6 ± 0.90 d) than FNS group (39.65 ± 2.84 min, 45.33 ± 9.63 ml and 4.87 ± 0.48 d) and MCS group (39.45 ± 3.10 min, 48.15 ± 7.88 ml and 5.04 ± 0.49 d) (p < 0.05). In addition, the time of fluoroscopy in FNS group (15.45 ± 3.67) was less than that in MCS group (26.3 ± 4.76) and DHS group (27.1 ± 5.67) (p < 0.05). The cost of FNS group(44.51 ± 2.99 thousand RMB) was significantly higher than the MCS and DHS groups. The FNS, MCS and DHS groups showed a similar mean length of femoral neck shortening (LFNS) and Harris score. The FNS, MCS and DHS groups showed a similar mean rate of AVN and internal fixation failure. CONCLUSIONS: Following successful fracture reduction, FNS, MCS, and DHS are effective for in the young femoral neck fractures. No difference was found in complications between the three groups. However, the reduced fluoroscopy time associated with FNS contributes to shorter operation durations. The adoption of minimally invasive techniques correlates with decreased blood loss and shorter hospital stays. Nevertheless, these advantages may be offset by the potential economic burden they impose.

Performance Enhancement of Tin-Based Perovskite Photodetectors through Bifunctional Cesium Fluoride Engineering.

Tin halide perovskites are rising as promising candidates for next-generation optoelectronic materials due to their good optoelectronic properties and relatively low toxicity. However, the high defect density and the easy oxidation of Sn2+ have limited their optoelectronic performance. Herein, we report the treatment of the FASnI3 (formamidinium tin, FA) perovskite film by a bifunctional cesium fluoride (CsF) additive, which improves the film quality and significantly enhances the photoelectric performance. The responsivity of the perovskite-based photodetector (PD) with an optimal CsF concentration of 15% is over 60 times larger than that of the PD without CsF. It indicates that both the Cs substitution and the fluoride anion additive from CsF inhibit the oxidation of Sn2+, optimize the crystal growth, and passivate the defects, demonstrating the dual roles of the CsF additive in improving the photoelectric performance. This work offers valuable insights into the additive selection for developing high-quality tin-based perovskite films and devices.

Clinical value of serum complement component 1q levels in the prognostic analysis of aneurysmal subarachnoid hemorrhage: a prospective cohort study.

Objective: To analyze the relationship between serum complement component 1q (C1q) levels and functional prognosis in patients with aneurysmal subarachnoid hemorrhage (aSAH), and to reveal its clinical value. Methods: In this prospective cohort study, we collected clinical data of aSAH patients admitted to the Department of Neurosurgery, Hangzhou First People's Hospital from January 2020 to October 2022. Parameters such as serum C1q levels, Hunt-Hess grade, modified Fisher grade, and the modified Rankin scale (mRS) at 3 months were included for evaluation. Patients were grouped based on the occurrence of delayed cerebral ischemia (DCI). Spearman rank correlation test and Kruskal-Wallis rank sum test were used to analyze the correlation between serum C1q levels, disease severity, and prognosis. Potential risk factors affecting prognosis and the occurrence of DCI were screened through Independent sample t-test or Mann-Whitney U test. Variables with significant differences (p < 0.05) were incorporated into a logistic regression model to identify independent risk factors affecting prognosis and DCI occurrence. Serum C1q levels were plotted as a ROC curve for predicting prognosis and DCI, and the area under the curve was calculated. Results: A total of 107 aSAH patients were analyzed. Serum C1q levels positively correlated with Hunt-Hess grade, modified Fisher grade and mRS (all p < 0.001). Significant differences were observed in C1q levels among different Hunt-Hess grade, mFisher grade and mRS (all p < 0.001). Notably, higher serum C1q levels were seen in the poor prognosis group and DCI group, and correlated with worse prognosis (OR = 36.927, 95%CI 2.003-680.711, p = 0.015), and an increased risk for DCI (OR = 17.334, 95%CI 1.161-258.859, p = 0.039). ROC analysis revealed the significant discriminative power of serum C1q levels for poor prognosis (AUC 0.781; 95%CI 0.673-0.888; p < 0.001) and DCI occurrence (AUC 0.763; 95%CI 0.637-0.888; p < 0.001). Higher C1q levels independently predicted a poor prognosis and DCI with equivalent predictive abilities to Hunt-Hess grade and modified Fisher grade (both p < 0.05). Conclusion: High levels of C1q in the blood is an independent risk factor for poor prognosis and the development of DCI in patients with aSAH. This can more objectively and accurately predict functional outcomes and the incidence of DCI. C1q may have a significant role in the mechanism behind DCI after aSAH.