Analysis of risk factors of suicidal ideation in adolescent patients with depression and construction of prediction model.

BACKGROUND: Major depressive disorder is a common mental illness among adolescents and is the largest disease burden in this age group. Most adolescent patients with depression have suicidal ideation (SI); however, few studies have focused on the factors related to SI, and effective predictive models are lacking. AIM: To construct a risk prediction model for SI in adolescent depression and provide a reference assessment tool for prevention. METHODS: The data of 150 adolescent patients with depression at the First People's Hospital of Lianyungang from June 2020 to December 2022 were retrospectively analyzed. Based on whether or not they had SI, they were divided into a SI group (n = 91) and a non-SI group (n = 59). The general data and laboratory indices of the two groups were compared. Logistic regression was used to analyze the factors influencing SI in adolescent patients with depression, a nomogram prediction model was constructed based on the analysis results, and internal evaluation was performed. Receiver operating characteristic and calibration curves were used to evaluate the model's efficacy, and the clinical application value was evaluated using decision curve analysis (DCA). RESULTS: There were differences in trauma history, triggers, serum ferritin levels (SF), high-sensitivity C-reactive protein levels (hs-CRP), and high-density lipoprotein (HDL-C) levels between the two groups (P < 0.05). Logistic regression analysis showed that trauma history, predisposing factors, SF, hs-CRP, and HDL-C were factors influencing SI in adolescent patients with depression. The area under the curve of the nomogram prediction model was 0.831 (95%CI: 0.763-0.899), sensitivity was 0.912, and specificity was 0.678. The higher net benefit of the DCA and the average absolute error of the calibration curve were 0.043, indicating that the model had a good fit. CONCLUSION: The nomogram prediction model based on trauma history, triggers, ferritin, serum hs-CRP, and HDL-C levels can effectively predict the risk of SI in adolescent patients with depression.

Phthalates Boost Natural Transformation of Extracellular Antibiotic Resistance Genes through Enhancing Bacterial Motility and DNA Environmental Persistence.

The environmental dissemination of extracellular antibiotic resistance genes (eARGs) in wastewater and natural water bodies has aroused growing ecological concerns. The coexisting chemical pollutants in water are known to markedly affect the eARGs transfer behaviors of the environmental microbial community, but the detailed interactions and specific impacts remain elusive so far. Here, we revealed a concentration-dependent impact of dimethyl phthalate (DMP) and several other types of phthalate esters (common water pollutants released from plastics) on the natural transformation of eARGs. The DMP exposure at an environmentally relevant concentration (10 µg/L) resulted in a 4.8-times raised transformation frequency of Acinetobacter baylyi but severely suppressed the transformation at a high concentration (1000 µg/L). The promotion by low-concentration DMP was attributed to multiple mechanisms, including increased bacterial mobility and membrane permeability to facilitate eARGs uptake and improved resistance of the DMP-bounded eARGs (via noncovalent interaction) to enzymatic degradation (with suppressed DNase activity). Similar promoting effects of DMP on the eARGs transformation were also found in real wastewater and biofilm systems. In contrast, higher-concentration DMP suppressed the eARGs transformation by disrupting the DNA structure. Our findings highlight a potentially underestimated eARGs spreading in aquatic environments due to the impacts of coexisting chemical pollutants and deepen our understanding of the risks of biological-chemical combined pollution in wastewater and environmental water bodies.

Functional Identification of HhUGT74AG11-A Key Glycosyltransferase Involved in Biosynthesis of Oleanane-Type Saponins in Hedera helix.

Hedera helix is a traditional medicinal plant. Its primary active ingredients are oleanane-type saponins, which have extensive pharmacological effects such as gastric mucosal protection, autophagy regulation actions, and antiviral properties. However, the glycosylation-modifying enzymes responsible for catalyzing oleanane-type saponin biosynthesis remain unidentified. Through transcriptome, cluster analysis, and PSPG structural domain, this study preliminarily screened four candidate UDP-glycosyltransferases (UGTs), including Unigene26859, Unigene31717, CL11391.Contig2, and CL144.Contig9. In in vitro enzymatic reactions, it has been observed that Unigene26859 (HhUGT74AG11) has the ability to facilitate the conversion of oleanolic acid, resulting in the production of oleanolic acid 28-O-glucopyranosyl ester. Moreover, HhUGT74AG11 exhibits extensive substrate hybridity and specific stereoselectivity and can transfer glycosyl donors to the C-28 site of various oleanane-type triterpenoids (hederagenin and calenduloside E) and the C-7 site of flavonoids (tectorigenin). Cluster analysis found that HhUGT74AG11 is clustered together with functionally identified genes AeUGT74AG6, CaUGT74AG2, and PgUGT74AE2, further verifying the possible reason for HhUGT74AG11 catalyzing substrate generalization. In this study, a novel glycosyltransferase, HhUGT74AG11, was characterized that plays a role in oleanane-type saponins biosynthesis in H. helix, providing a theoretical basis for the production of rare and valuable triterpenoid saponins.

A longitudinal study on the effects of social support on self-stigma, psychiatric symptoms, and personal and social functioning in community patients with severe mental illnesses in China.

BACKGROUND: Few studies have examined whether social support contributes to better consequences among chronic patients with severe mental illnesses (SMI) in their community recovery stage and whether self-stigma would be a mechanism through which social support impacts psychiatric symptoms and personal and social functioning. AIMS: This study aimed to examine prospective associations of social support with long-term self-stigma, psychiatric symptoms, and personal and social functioning, and to investigate whether self-stigma would mediate the associations of social support with psychiatric symptoms and personal and social functioning among patients with SMI. METHODS: A total of 312 persons with SMI (schizophrenia and bipolar disorder) in their community recovery stage participated in the study. Social support, self-stigma, psychiatric symptoms, and personal and social functioning were evaluated at baseline. The follow-up assessment was conducted at 6 months with the baseline measures except for social support. Hierarchical linear regression and mediation analysis were performed. RESULTS: The results showed that baseline social support predicted decreases in stigma (ß = -.115, p = .029) and psychiatric symptoms (ß = -.193, p < .001), and increases in personal and social functioning (ß = .134, p = .008) over 6 months, after adjusting for relevant covariates. Stigma at 6 months partially mediated the association between baseline social support and 6-month psychiatric symptoms (indirect effect: ß = -.043, CI [-0.074, -0.018]). Stigma and psychiatric symptoms at 6 months together mediated the association between baseline social support and 6-month personal and social functioning (indirect effect: ß = .084, 95% CI [0.029, 0.143]). CONCLUSION: It is necessary to provide comprehensive social support services and stigma reduction interventions at the community level to improve the prognosis of SMI.

Altered static and dynamic functional brain network in knee osteoarthritis: A resting-state functional magnetic resonance imaging study: Static and dynamic FNC in KOA.

This study aimed to investigate altered static and dynamic functional network connectivity (FNC) and its correlation with clinical symptoms in patients with knee osteoarthritis (KOA). One hundred and fifty-nine patients with KOA and 73 age- and gender-matched healthy subjects (HS) underwent resting-state functional magnetic resonance imaging (rs-fMRI) and clinical evaluations. Group independent component analysis (GICA) was applied, and seven resting-state networks were identified. Patients with KOA had decreased static FNC within the default mode network (DM), visual network (VS), and cerebellar network (CB) and increased static FNC between the subcortical network (SC) and VS (p < 0.05, FDR corrected). Four reoccurring FNC states were identified using k-means clustering analysis. Although abnormalities in dynamic FNCs of KOA patients have been found using the common window size (22 TR, 44 s), but the results of the clustering analysis were inconsistent when using different window sizes, suggesting dynamic FNCs might be an unstable method to compare brain function between KOA patients and HS. These recent findings illustrate that patients with KOA have a wide range of abnormalities in the static and dynamic FNCs, which provided a reference for the identification of potential central nervous therapeutic targets for KOA treatment and might shed light on the other musculoskeletal pain neuroimaging studies.

Correlation Between Cortical Thickness Abnormalities of the Olfactory Sulcus and Olfactory Identification Disorder and Persistent Auditory Verbal Hallucinations in Chinese Patients With Chronic Schizophrenia.

BACKGROUND AND HYPOTHESIS: Persistent auditory verbal hallucinations (pAVHs) and olfactory identification impairment are common in schizophrenia (SCZ), but the neuroimaging mechanisms underlying both pAVHs and olfactory identification impairment are unclear. This study aimed to investigate whether pAVHs and olfactory identification impairment in SCZ patients are associated with changes in cortical thickness. STUDY DESIGN: In this study, cortical thickness was investigated in 78 SCZ patients with pAVHs (pAVH group), 58 SCZ patients without AVHs (non-AVH group), and 83 healthy controls (HC group) using 3T magnetic resonance imaging. The severity of pAVHs was assessed by the Auditory Hallucination Rating Scale. Olfactory identification deficits were assessed using the Odor Stick Identification Test for Japanese (OSIT-J). In addition, the relationship between the severity of pAVHs and olfactory identification disorder and cortical thickness abnormalities was determined. STUDY RESULTS: Significant reductions in cortical thickness were observed in the right medial orbital sulcus (olfactory sulcus) and right orbital sulcus (H-shaped sulcus) in the pAVH group compared to both the non-AVH and HC groups (P < .003, Bonferroni correction). Furthermore, the severity of pAVHs was found to be negatively correlated with the reduction in cortical thickness in the olfactory sulcus and H-shaped sulcus. Additionally, a decrease in cortical thickness in the olfactory sulcus showed a positive correlation with the OSIT-J scores (P < .05, false discovery rate correction). CONCLUSIONS: Cortical thickness abnormalities in the olfactory sulcus may be a common neuroimaging mechanism for pAVHs and olfactory identification deficits in SCZ patients.

Dietary inflammatory index is associated with metabolic dysfunction-associated fatty liver disease among United States adults.

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is presently the most prevalent chronic liver disorder globally that is closely linked to obesity, dyslipidemia metabolic syndrome, and type 2 diabetes mellitus (T2DM). Its pathogenesis is strongly associated with inflammation, and diet is a major factor in reducing inflammation. However, current research has focused primarily on exploring the relationship between diet and NAFLD, with less research on its link to MAFLD. Methods: In this research, using dietary inflammatory index (DII) as a measure to assess dietary quality, we analyzed the relationship between diet and MAFLD. Data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018, including 3,633 adults with complete DII and MAFLD, were used to develop cross-sectional analyses. Logistic regression analysis was adapted for investigating the relationship between DII and MAFLD development. Additionally, subgroup analysis and threshold effect analysis were carried out. Results: A positive link between DII and MAFLD was found in the fully adjusted model (OR = 1.05; 95%CI, 1.00-1.11, p < 0.05). Subgroup analysis indicated that there was no significant dependence for the connection between DII and MAFLD except for the subgroup stratified by age. Compared with other age groups, people with MAFLD had 20% higher DII scores than non-MAFLD participants in those aged 20-41 years old (OR = 1.20; 95%CI, 1.08-1.33, p < 0.001). Furthermore, we found a U-shaped curve with an inflection point of 3.06 illustrating the non-linear connection between DII and MAFLD. Conclusion: As a result, our research indicates that pro-inflammatory diet may increase the chance of MAFLD development, thus improved dietary patterns as a lifestyle intervention is an important strategy to decrease the incidence of MAFLD.

Targeting RCC1 to block the human soft-tissue sarcoma by disrupting nucleo-cytoplasmic trafficking of Skp2.

Soft-tissue sarcomas (STS) emerges as formidable challenges in clinics due to the complex genetic heterogeneity, high rates of local recurrence and metastasis. Exploring specific targets and biomarkers would benefit the prognosis and treatment of STS. Here, we identified RCC1, a guanine-nucleotide exchange factor for Ran, as an oncogene and a potential intervention target in STS. Bioinformatics analysis indicated that RCC1 is highly expressed and correlated with poor prognosis in STS. Functional studies showed that RCC1 knockdown significantly inhibited the cell cycle transition, proliferation and migration of STS cells in vitro, and the growth of STS xenografts in mice. Mechanistically, we identified Skp2 as a downstream target of RCC1 in STS. Loss of RCC1 substantially diminished Skp2 abundance by compromising its protein stability, resulting in the upregulation of p27Kip1 and G1/S transition arrest. Specifically, RCC1 might facilitate the nucleo-cytoplasmic trafficking of Skp2 via direct interaction. As a result, the cytoplasmic retention of Skp2 would further protect it from ubiquitination and degradation. Notably, recovery of Skp2 expression largely reversed the phenotypes induced by RCC1 knockdown in STS cells. Collectively, this study unveils a novel RCC1-Skp2-p27Kip1 axis in STS oncogenesis, which holds promise for improving prognosis and treatment of this formidable malignancy.

A bibliometric analysis of research on pediatric preoperative anxiety (2007-2022).

Objective: This study aimed to analyze the current state of research on preoperative anxiety in children through CiteSpace, VOSviewer, and the identification of hot spots and frontiers. Method: Relevant data were retrieved from the Web of Science Core Collection using the search terms children and preoperative anxiety. Data were analyzed using VOSviewer (version 1.6.18), CiteSpace (5.7. R5) software, and Scimago Graphica. Results: A total of 622 articles were published between 2007 and 2022, with an increasing trend over time. Kain, Zeev N. (13; 2.09%) and Dalhousie University (15; 2.41%) were the most influential authors and most prolific institutions, respectively. The United States (121; 19.45%) was the country with the most publications. Pediatric anesthesia (55; 8.84%) had the most publications. High-frequency keywords were categorized into three themes, including nonpharmacologic interventions for preoperative anxiety in children, preoperative medications, and risk factors for anxiety; of these, "predictor" (38; 2016) and "sedative premedication" (20; 2016) were the most studied keywords over the past 6 years. "Distraction" (67; 2019) and "dexmedetomidine" (65; 2019) have been the main areas of interest in recent years. Conclusion: Research on preoperative anxiety in children has been the focus of increasing attention over the past fifteen years, with the majority of publications from high-income countries. This review provides a useful perspective for understanding research trends, hot topics, and research gaps in this expanding field.

Rapid Plasma Electrolytic Oxidation Synthesis of Intermetallic PtBi/MgO/Mg Monolithic Catalyst for Efficient Removal of Organic Pollutants.

The intermetallic PtBi/MgO/Mg monolithic catalyst was first prepared using non-equilibrium plasma electrolytic oxidation (PEO) technology. Spherical aberration-corrected transmission electron microscope (ACTEM) observation confirms the successful synthesis of the PtBi intermetallic structure. The efficiency of PtBi/Mg/MgO catalysts in catalyzing the reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) in the presence of NaBH4 was demonstrated. The activity factor for the catalyst is 31.8 s-1 g-1, which is much higher than reported values. In addition, the resultant catalyst also exhibits excellent catalytic activity in the organic pollutant reaction of p-nitrobenzoic acid (p-NBA) and methyl orange (MO). Moreover, benefiting from ordered atomic structures and the half-embedded PtBi nanoparticles (NPs), the catalyst demonstrates excellent stability and reproducibility in the degradation of 4-NP. This study provides an example of a simple method for the preparation of intermetallic structures as catalysts for organic pollutant degradation.

Cross-coupling of organic fluorides with allenes: a silyl-radical-relay pathway for the construction of α-alkynyl-substituted all-carbon quaternary centres.

Controlling the transformation of versatile and reactive allenes is a considerable challenge. Herein, we report an efficient silylboronate-mediated cross-coupling reaction of organic fluorides with allenes to construct a series of sterically demanding α-ethynyl-containing all-carbon quaternary centers (ACQCs), using catalyst-free silyl-radical-relay reactions to selectively functionalize highly inert C-F bonds in organic fluorides. The key to the success of this transformation lies in the radical rearrangement of an in situ-generated allenyl radical to form a bulky tertiary propargyl radical; however, the transformation does not show efficiency when using the propargyl isomer directly. This unique reaction enables the cross-coupling of a tertiary carbon radical center with a C(sp2)-F bond or a benzylic C(sp3)-F bond. α-Ethynyl-containing ACQCs with (hetero)aromatic substituents and benzyl were efficiently synthesized in a single step using electronically and sterically diverse organic fluorides and allenes. The practical utility of this protocol is showcased by the late-stage functionalization of bioactive molecules and the modification of a liquid crystalline material.

Anti-Inflammatory Salicin Derivatives from the Barks of Salix tetrasperma.

The genus Salix L. is traditionally used in folk medicine to alleviate pain caused by various kinds of inflammation. In the present study, 10 undescribed salicin derivatives along with 5 known congeners were isolated from the barks of Salix tetrasperma, and their structures were elucidated by spectroscopic analyses, single-crystal X-ray diffraction, electronic circular dichroism (ECD) calculations, and chemical conversions. Compounds 4-6 significantly inhibited NO production in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages, and the most active 4 obviously suppressed the production of IL-1ß and IL-6 and decreased iNOS and COX-2 expression in a dose-dependent manner. Further Western blotting analysis revealed that the anti-inflammatory mechanism of 4 is possibly mediated through the MAPK and NF-κB signaling pathways.

Nucleus-targeting DNase I self-assembly delivery system guided by pirarubicin for programmed multi-drugs release and combined anticancer therapy.

The cell nucleus serves as the pivotal command center of living cells, and delivering therapeutic agents directly into the nucleus can result in highly efficient anti-tumor eradication of cancer cells. However, nucleus-targeting drug delivery is very difficult due to the presence of numerous biological barriers. Here, three antitumor drugs (DNase I, ICG: indocyanine green, and THP: pirarubicin) were sequentially triggered protein self-assembly to produce a nucleus-targeting and programmed responsive multi-drugs delivery system (DIT). DIT consisted of uniform spherical particles with a size of 282 ± 7.7 nm. The acidic microenvironment of tumors and near-infrared light could successively trigger DIT for the programmed release of three drugs, enabling targeted delivery to the tumor. THP served as a nucleus-guiding molecule and a chemotherapy drug. Through THP-guided DIT, DNase I was successfully delivered to the nucleus of tumor cells and killed them by degrading their DNA. Tumor acidic microenvironment had the ability to induce DIT, leading to the aggregation of sufficient ICG in the tumor tissues. This provided an opportunity for the photothermal therapy of ICG. Hence, three drugs were cleverly combined using a simple method to achieve multi-drugs targeted delivery and highly effective combined anticancer therapy.

Enhancing cancer therapy: The role of drug delivery systems in STAT3 inhibitor efficacy and safety.

The signal transducer and activator of transcription 3 (STAT3), a member of the STAT family, resides in the nucleus to regulate genes essential for vital cellular functions, including survival, proliferation, self-renewal, angiogenesis, and immune response. However, continuous STAT3 activation in tumor cells promotes their initiation, progression, and metastasis, rendering STAT3 pathway inhibitors a promising avenue for cancer therapy. Nonetheless, these inhibitors frequently encounter challenges such as cytotoxicity and suboptimal biocompatibility in clinical trials. A viable strategy to mitigate these issues involves delivering STAT3 inhibitors via drug delivery systems (DDSs). This review delineates the regulatory mechanisms of the STAT3 signaling pathway and its association with cancer. It offers a comprehensive overview of the current application of DDSs for anti-STAT3 inhibitors and investigates the role of DDSs in cancer treatment. The conclusion posits that DDSs for anti-STAT3 inhibitors exhibit enhanced efficacy and reduced adverse effects in tumor therapy compared to anti-STAT3 inhibitors alone. This paper aims to provide an outline of the ongoing research and future prospects of DDSs for STAT3 inhibitors. Additionally, it presents our insights on the merits and future outlook of DDSs in cancer treatment.

Effects of Baduanjin practice on emotional, attention and cognitive function in acupuncturists: protocol for a clinical randomized controlled neuroimaging trial.

Background: In Chinese medicine, the mental focus and emotional stability of acupuncturists are key to optimal clinical outcomes. Many renowned acupuncturists utilize Traditional Chinese Qigong practices to enhance their concentration and emotional regulation abilities. Nevertheless, the existing literature lacks comprehensive evidence addressing this matter. Methods: This study will enroll 99 acupuncturists and randomly allocate them to one of three groups: Baduanjin, aerobic exercise, or a waiting-list control. The Baduanjin group will undertake 24 weeks of training, with three one-hour sessions weekly. The aerobic group will engage in brisk walking for the same duration and frequency. The control group will not receive any specific training. Assessments of emotion regulation, attention, cognitive functions, finger sensation, and athletic ability will be conducted at baseline (-1 week), mid-intervention (12 weeks), and post-intervention (24 weeks). Additionally, 20 participants from each group will undergo fMRI scans before and after the intervention to explore brain functional and structural changes relating to emotion, attention, cognition, motor skills, and sensory perception. Discussion: This study aims to contribute valuable insights into the effectiveness of Qigong practice, specifically Baduanjin, in enhancing emotional regulation, attention, and cognitive functions in acupuncturists and to investigate the neuroimaging mechanisms behind these effects. Ethics and dissemination: Approved by the Sichuan Regional Ethics Review Committee on Traditional Chinese Medicine (No. 2023KL - 118) and adhering to the Declaration of Helsinki. Results will be shared through policy briefs, workshops, peer-reviewed journals, and conferences.Clinical trial registrationwww.chictr.org.cn, ChiCTR2300076447.

Molecular features of gastroenteropancreatic neuroendocrine carcinoma: A comparative analysis with lung neuroendocrine carcinoma and digestive adenocarcinomas.

Objective: There is an ongoing debate about whether the management of gastroenteropancreatic (GEP) neuroendocrine carcinoma (NEC) should follow the guidelines of small-cell lung cancer (SCLC). We aim to identify the genetic differences of GEPNEC and its counterpart. Methods: We recruited GEPNEC patients as the main cohort, with lung NEC and digestive adenocarcinomas as comparative cohorts. All patients undergone next-generation sequencing (NGS). Different gene alterations were compared and analyzed between GEPNEC and lung NEC (LNEC), GEPNEC and adenocarcinoma to yield the remarkable genes. Results: We recruited 257 patients, including 99 GEPNEC, 57 LNEC, and 101 digestive adenocarcinomas. Among the mutations, KRAS, RB1, TERT, IL7R, and CTNNB1 were found to have different gene alterations between GEPNEC and LNEC samples. Specific genes for each site were revealed: gastric NEC ( TERT amplification), colorectal NEC ( KRAS mutation), and bile tract NEC ( ARID1A mutation). The gene disparities between small-cell NEC (SCNEC) and large-cell NEC (LCNEC) were KEAP1 and CDH1. Digestive adenocarcinoma was also compared with GEPNEC and suggested RB1, APC, and KRAS as significant genes. The TP53/ RB1 mutation pattern was associated with first-line effectiveness. Putative targetable genes and biomarkers in GEPNEC were identified in 22.2% of the patients, and they had longer progression-free survival (PFS) upon targetable treatment [12.5 months vs. 3.0 months, HR=0.40 (0.21-0.75), P=0.006]. Conclusions: This work demonstrated striking gene distinctions in GEPNEC compared with LNEC and adenocarcinoma and their clinical utility.

In Situ Implanting ZrW2 O7 (OH)2 (H2 O)2 Nanorods into Hierarchical Functionalized Metal-Organic Framework via Solvent-Free Approach for Upgrading Catalytic Performance.

Host-guest catalyst provides new opportunities for targeted applications and the development of new strategies for preparing host-guest catalysts is highly desired. Herein, an in situ solvent-free approach is developed for implanting ZrW2 O7 (OH)2 (H2 O)2 nanorods (ZrW-NR) in nitro-functionalized UiO-66(Zr) (UiO-66(Zr)-NO2 ) with hierarchical porosity, and the encapsulation of ZrW-NR enables the as-prepared host-guest catalyst remarkably enhanced catalytic performance for both for oxidative desulfurization (ODS) and acetalization reactions. ZrW-NR@UiO-66(Zr)-NO2 can eliminate 500 ppm sulfur within 9 min at 40 °C in ODS, and can transform 5.6 mmol benzaldehyde after 3 min at room temperature in acetalization reaction. Its turnover frequencies reach 72.3 h-1 at 40 °C for ODS which is 33.4 times higher than UiO-66(Zr)-NO2 , and 28140 h-1 for acetalization which is the highest among previous reports. Density functional theory calculation result indicates that the W sites in ZrW-NR can decompose H2 O2 to WVI -peroxo intermediates that contribute to catalytic activity for the ODS reaction. This work opens a new solvent-free approach for preparing MOFs-based host-guest catalysts to upgrade their redox and acid performance.

Microenvironment-responsive metal-phenolic network release platform with ROS scavenging, anti-pyroptosis, and ECM regeneration for intervertebral disc degeneration.

Intervertebral disc degeneration (IVDD) can be caused by aging, injury, and genetic factors. The pathological changes associated with IVDD include the excessive accumulation of reactive oxygen species (ROS), cellular pyroptosis, and extracellular matrix (ECM) degradation. There are currently no approved specific molecular therapies for IVDD. In this study, we developed a multifunctional and microenvironment-responsive metal-phenolic network release platform, termed TMP@Alg-PBA/PVA, which could treat (IL-1ß)-induced IVDD. The metal-phenolic network (TA-Mn-PVP, TMP) released from this platform targeted mitochondria to efficiently scavenge ROS and reduce ECM degradation. Pyroptosis was suppressed through the inhibition of the IL-17/ERK signaling pathway. These findings demonstrate the versatility of the platform. And in a rat model of IVDD, TMP@Alg-PBA/PVA exhibited excellent therapeutic effects by reducing the progression of the disease. TMP@Alg-PBA/PVA, therefore, presents clinical potential for the treatment of IVDD.

Construction of an Au12Cd2 nanocluster with circularly polarized luminescence by a metal- and ligand-exchange strategy.

Excellent luminescence properties and unique chiral structures enable nanoclusters to be a novel class of circularly polarized luminescence (CPL) materials, and their precise structures facilitate the clarification of structure-activity relationships. However, efficiently preparing nanoclusters with CPL properties is still a great challenge. In this work, the luminescent properties as well as the molecular symmetry were simultaneously manipulated to transform the centrosymmetric Au14Cd1 into a chiral Au12Cd2 nanocluster, which has CPL properties. In detail, Cd doping and chiral-ligand exchange were performed simultaneously on the Au14Cd1 nanocluster to realize its photoluminescence enhancement and chiral-framework construction by increasing the alloying degree which is defined as deep-alloying and chiral ligand induction at the same time, resulting in the formation of an Au12Cd2 nanocluster with CPL properties. Further investigations revealed an increased alloying degree in the structure-maintained M6 kernel of Au12Cd2, which results in a 15-fold enhancement in quantum yield.

Primary cilia restrict autoinflammation by mediating PD-L1 expression.

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