Objective: To investigate the association between monocyte to high-density lipoprotein cholesterol ratio (MHR) and periodontitis and to provide new epidemiologic evidence on the factors affecting periodontitis. Methods: Data on MHR, periodontitis, and other covariates were selected from the NHANES(National Health and Nutrition Examination) database for 3 cycles of subjects in 2009-2010, 2011-2012, and 2013-2014, and a total of 8 456 study subjects were included. The study participants were grouped according to the prevalence of periodontitis (presence or absence), and three regression models (unadjusted covariates, partially adjusted covariates, and fully adjusted covariates) were constructed to analyze the relationship between MHR and periodontitis by using a weighted logistic regression method with stepwise adjustment for confounders. MHR was divided into four groups from Q1 to Q4 according to quartiles from small to large for weighted trend analysis, and the nonlinear relationship between MHR (continuous) and periodontitis was analyzed using a restricted cubic spline with subgroup analysis and sensitivity analysis. Results: All three logistic regression models showed a positive association between MHR and periodontitis (OR = 2.92, 95%CI: 2.14-3.99, P<0.001 (not adjusted); OR = 1.97, 95%CI: 1.39-2.78, P<0.001 (partially adjusted); OR = 1.62, 95%CI: 1.10-2.39, P = 0.017 (fully adjusted)). Trend analysis showed a significantly higher risk of developing periodontitis in the Q4 group compared with the Q1 group in both single (OR = 1.92, 95% CI: 1.58-2.33, P<0.001) and multifactorial analyses (OR = 1.30, 95% CI: 1.03-1.64, P = 0.029). Restricted cubic spline results did not support a nonlinear relationship between MHR and periodontitis (P for nonlinear>0.05), subgroup analysis showed no significant interaction between the covariates and MHR (P>0.05), and sensitivity analysis also showed a positive correlation between MHR and periodontitis (OR = 1.67, 95%CI: 1.31-2.14, P<0.001). Conclusion MHR is positively associated with the risk of developing periodontitis.

ObjectiveTo investigate the pharmacodynamic effects of Houshihei San （HSHS） recorded with the effects of treating wind and limb heaviness on muscle tissue injury after middle cerebral artery occlusion （MCAO） in rats through the ferroptosis pathway. MethodsThirty SD male rats were selected and randomly grouped as follows： sham， MCAO， deferoxamine mesylate， high-dose HSHS （HSHS-H， 0.54 g·kg^-1）， and low-dose HSHS （HSHS-L， 0.27 g·kg^-1）， with 6 rats in each group. A laser scattering system was used to evaluate the stability of the MCAO model， and rats were administrated with corresponding agents by gavage for 7 days. During the administration period， behavioral， imaging and other methods were used to systematically evaluate the skeletal muscle tissue injury after MCAO and the therapeutic effect in each administration group. Hematoxylin-eosin staining was employed to evaluate the cross-section of muscle cells. Subsequently， immunohistochemistry was used to detect tumor suppressor p53 and glutathione peroxidase 4 （GPX4） in the soleus tissue. Western blot was employed to determine the protein levels of p53， GPX4， myogenic differentiation 1 （MyoD1）， nuclear factor E₂-related factor 2 （Nrf2）， Myostatin， solute carrier family 7 member 11 （SLC7A11）， muscle ring-finger protein-1 （MuRF1）， and muscle atrophy F-box protein （MAFbx） to verify the therapeutic effect in each group. ResultsCompared with the MCAO group， HSHS enhanced the locomotor ability and promoted muscle regeneration， which suggested that the pharmacological effects of HSHS were related to the inhibition of muscle tissue ferroptosis to reduce the expression of muscle atrophy factors. Behavioral and imaging results suggested that compared with the MCAO group， HSHS ameliorated neurological impairments in rats on day 7 （P<0.01）， enhanced 5-min locomotor distance and postural control （P<0.01）， strengthened grasping power and promoted muscle growth （P<0.01）， stabilized skeletal muscle length and weight （P<0.01）， and increased the cross-section of muscle cells （P<0.01）. Compared with the MCAO group， HSHS promoted the increases in glutathione and superoxide dismutase content and inhibited the increase in malondialdehyde content （P<0.05，P<0.01）. Ferroptosis pathway-related assays suggested that HSHS reduced the p53-positive cells and increased the GPX4-positive cells （P<0.01）. HSHS ameliorated muscle function decline after stroke by promoting the expression of GPX4， Nrf2， SLC7A11， and MyoD1 and inhibiting the expression of p53， Myostatin， MurRF1， and MAFbx to reduce ferroptosis in the muscle （P<0.01）. ConclusionHSHS， prepared with reference to the method in the Synopsis of Golden Chamber， can simultaneously reduce the myolysis and increase the protein synthesis in the skeletal muscle tissue after ischemic stroke by regulating the ferroptosis pathway.

Peptide-drug conjugates (PDCs) have emerged as a promising modality in precision oncology, enabling targeted delivery of cytotoxic payloads while minimizing off-target toxicity. The integration of covalent warheads, such as those based on sulfur(VI) fluoride exchange (SuFEx) chemistry, enhances drug-target residence time and tumor accumulation. However, existing screening methods for covalent peptide (CP) libraries require post-translational warhead conjugation, limiting throughput. Here, we present an integrated mRNA display platform that incorporates covalent warheads during ribosomal synthesis, enabling efficient screening of ultra-diverse covalent macrocyclic peptide libraries (>10¹³ variants). This approach, using site-specific incorporation of N-chloroacetyl-d-phenylalanine and fluorosulfate-l-tyrosine, accelerated the discovery of irreversibly binding (K _i = 3.58 μmol/L) Nectin-4-targeting peptide CP-N1-N₃ via proximity-triggered SuFEx. The peptide was further conjugated to cytotoxic payloads, yielding the covalent PDC CP-N1-MMAE with potent cytotoxicity (IC₅₀ ≈ 43 nmol/L) against MDA-MB-468 cells. This platform establishes a new paradigm for precision covalent drug discovery.

Nine novel compounds, comprising seven tetrahydroanthraquinones (auxarthrolones A-G, 1-7), a γ-butenolide glycoside (malfilamentoside E, 26), and a γ-butenolide (auxarthrolide A, 27), together with eighteen known compounds (8-25) were isolated from rice-based solid culture of Auxarthron umbrinum (A. umbrinum) DSM3193 using the one strain many compounds (OSMAC) approach. The structural elucidation of these compounds was accomplished through nuclear magnetic resonance (NMR), mass spectrometry (MS), and NMR calculation combined with DP4+ analysis or MAEΔΔδ parameter, while the absolute configurations of new compounds were established through single-crystal X-ray diffraction, electronic circular dichroism (ECD) spectroscopic data analysis and/or chemical derivatization. Austrocortilutein (10) and auxarthrol H (14) demonstrated moderate cytotoxicity against U87 and U251 [half maximal inhibitory concentration (IC₅₀) 3.5-12.1 μmol·L^-1]. Additionally, auxarthrolone A (1), auxarthrol H (14), eupolyphagin B (15), and 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone (17) exhibited torsional effects on fibroblast proliferation challenges induced by oleic acid, thus demonstrating fibroblast proliferation-promoting activity.
4-Butyrolactone/pharmacology* ; Molecular Structure ; Anthraquinones/pharmacology* ; Humans ; Animals ; Mice ; Cell Line, Tumor ; Magnetic Resonance Spectroscopy

As a medicinal and edible fungus, Inonotus obliquus has a long history of folk application in Russia, Japan, and Northeast China. It is rich in terpenoids, steroids, polysaccharides, phenols, alkaloids, etc, and exhibits pharmacological activities including anti-tumor, hypoglycemic, anti-inflammatory, antioxidant, and lipid-lowering effects. Among these, lanostane-type tetracyclic triterpenes represent its characteristic constituents. This review systematically summarizes the research progress on the chemical components isolated and identified from I. obliquus and their pharmacological activities in recent years. The structures of terpenoids, steroids, and phenolic compounds are compiled and illustrated, with a particular focus on the skeletal types and structural characteristics of lanostane-type tetracyclic triterpenes. This work aims to provide some reference for the further investigation and comprehensive development and utilization of I. obliquus.

Skeletal class Ⅱ malocclusion is characterized by maxillary protrusion,mandibular retrognathia,or a combination of both,and often accompanied by vertical dimensional discrepancies;treatment is complex,and combined orthodontic-orthognathic surgery is needed for the adult patients.Clear aligner therapy has gradually been applied in complex orthodontic cases.However,limited cases have been reported domestically and internationally regarding the application of clear aligner therapy combined with orthognathic surgery.This article presented a case of a patient with skeletal class Ⅱ high-angle malocclusion treated with the combined therapy and analyzed the clinical efficacy of the treatment appraoch to provide reference for the clinical practice.Extraction of impacted wisdom teeth 18,28,38,and 48,as well as orthodontic teeth 15,25,34,and 44,was performed in stages before orthodontic treatment.Clear aligner therapy was used for preoperative orthodontics.In sagittal plane,a super-complete class Ⅱ canine and molar relationship and a 13-14 mm overjet of the anterior teeth were established.The maxillary and mandibular arch morphology was matched horizontally.The orthognathic surgery included maxillary LeFort Ⅰ osteotomy,bilateral sagittal split ramus osteotomy(BSSRO)and chinplasty.Fine occlusal adjustment was conducted after operation.After treatment,the skeletal relationship between upper and lower jaw was corrected to normal;subspinale-nasion-supramental angle(ANB)was improved from 12.3° to 4.7°;the patient established the class Ⅰ canine and molar relationship,with normal overjet and overbite;root parallelism was good and there was no obvious root resorption;the facial soft tissue profile was significantly improved,and nasion-subnasale-pogonion angle(N-Sn-Pg)was improved from 143.9° to 162.8°.The curative effect was stable 1 year after operation.Clear aligner therapy can efficiently complete combined orthodontic and orthodontic surgery in the complex cases.Compared with the fixed appliance,it is more beneficial to the patients'need for beauty and the maintenance of periodontal health.

Objective: To elucidate the molecular mechanism by which prohibitin 2(PHB2) mediates periodontitis-induced bone tissue inflammation through regulating the nuclear factor kappa B(NF-κB) signaling pathway and its role in irreversible alveolar bone resorption. Methods: Quantitative real-time reverse transcription polymerase chain reaction(qRT-PCR) and immunohistochemistry(IHC) were used to detect the expression differences of inflammatory factors and PHB2 in healthy and inflamed alveolar bone tissues of mice in vivo. In vitro, an inflammatory model was established using lipopolysaccharide(LPS)-induced a mouse calvaria-derived preosteoblastic cell line, subclone E1(MC3T3-E1) cells. Western blot and qRT-PCR were used to clarify the regulatory relationship between PHB2 and inflammatory factors, and immunofluorescence staining was performed to observe changes in PHB2 subcellular localization. PHB2 overexpression plasmids were constructed using molecular cloning, and RNA interference was employed to knock down PHB2 expression to assess its regulatory role in inflammation. Based on RNA-seq data, differential expression analysis based on the negative binomial distribution, version 2(DESeq2) was used for differential expression analysis, and kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment along with gene ontology(GO) functional annotation were performed to identify key signaling pathways and differentially expressed genes. Results: In the mouse periodontitis model, PHB2 expression was significantly upregulated in alveolar bone tissues. In the in vitro inflammatory cell model, PHB2 levels positively correlated with interleukin(IL)-6, IL-1β, and tumor necrosis factor-alpha(TNF-α) levels, and its subcellular localization shifted during inflammation. RNA-seq data and the detection of the level of phosphorylation of p65 protein(p-p65) demonstrated that PHB2 exacerbated inflammatory responses through the NF-κB signaling pathway and was mechanistically linked to upregulation of the upstream chemokine C-X-C motif chemokine ligand 10(CXCL10). Conclusion PHB2 aggravates LPS-induced periodontitis inflammation via the NF-κB signaling pathway, providing new insights into the molecular mechanisms underlying the development of periodontitis.

Targeted delivery of antibody bound to antigen is a precise drug delivery mode. It is regarded as one of the ideal targeted drug delivery modes due to its high specificity and affinity, which opens up a new way to successfully solve the problem of poor selectivity of chemotherapy drugs in antitumor therapy. Currently, the research on antibody drug conjugates(ADCs) that bind monoclonal antibodies to target antigens has become a research hotspot of molecular targeted therapy. This paper reviews the mechanism of action, targeting strategies and progress in the targeted delivery of ADCs, in order to provide reference for the clinical development of new ADCs.

Objective To investigate the effect of resveratrol(RSV)in the treatment of peri-implantitis in a murine model and its effect on nuclear factor kappa-B(NF-κB)signaling and mitogen-activated protein kinase(MAPKs)signal-ing.Methods This study has been reviewed and approved by the Ethics.After extracting the right maxillary molars of 40 C57BL/6 mice and allowing them to heal naturally for 8 weeks,implants were implanted at the site of the first molar.The mice were randomly divided into a control group,a mouse peri implantitis model group,a low-dose group of 20 mg/kg resveratrol(RSV-L),and a high-dose group of 40 mg/kg resveratrol(RSV-H).After 4 weeks of implant implantation,a silk thread ligation induced peri implantitis model was established in all mice except for the control group.The model group received intervention with physiological saline by gavage,while the drug group received intervention with resvera-trol by gavage for 6 consecutive weeks.After 6-week treatment,observe the swelling of the gums around the implant and measure the bone resorption around the mouse implant using micro CT.Enzyme linked immunosorbent assay(ELISA)was used to detect the levels of tumor necrosis factor alpha(TNF-α)and interleukin-6(IL-6)in gingival crevicular fluid.HE staining was used to observe the infiltration of inflammatory cells in the surrounding tissues of mouse implants.Pro-tein expression level and phosphorylation level of extracellular regulated protein kinases(ERK),p-ERK,c-Jun N-termi-nal kinase(JNK),p-JNK,p38 mitogen activated protein kinase(p38 MAPK),p-p38MAPK,nuclear factor kappa-B(NF-κB),p-NF-κB,nuclear factor-κB inhibitory protein(IκBα),p-IκBα in MAPKs/NF-κB signaling pathway were detected by Western blot(WB).Results Resveratrol group showed reduced tissue edema and decreased alveolar bone resorp-tion.Among them,the high-dose resveratrol group had lighter tissue edema and weaker bone resorption compared to the low-dose group.The micro CT results showed that significant changes in the bone level around the implant were observed in the model group mice at four sites:proximal,distal,buccal,and palatal.High dose resveratrol intervention reduced al-veolar bone resorption(P＜0.05);compared with the low-dose group,the high-dose group showed a decrease in palatal bone resorption(P＜0.05),while there was no significant difference in absorption between the mesial,distal,and buccal sides(P＞0.05).The ELISA results showed that compared with the model group,the levels of TNF-α and IL-6 in the gingival crevicular fluid of mice in the low-dose and high-dose resveratrol groups were lower(P＜0.05).The IL-6 in the gingival crevicular fluid of mice in the high-dose resveratrol group was lower than that in the low-dose group(P＜0.05).However,there was no significant difference in TNF-α levels between the two groups.HE staining showed a decrease in inflammatory cell infiltration in mice after treatment with resveratrol.The WB results showed that compared with the con-trol group,the expression levels of p-Erk,p-JNK,p-p38MAPK,p-IκA,and p-NF-κB phosphorylated proteins in the gingi-val tissue of the model group mice were significantly increased(P＜0.01).The resveratrol treatment group significantly inhibited the phosphorylation of p-Erk,p-JNK,p-p38MAPK,p-IκA,and p-NF-κB proteins.Compared with the low-dose group,the high-dose group inhibited the phosphorylation of MAPKs/NF-κB signaling pathway related proteins more sig-nificantly(P＜0.05).Conclusion Resveratrol protect ligature induced peri-implantitis murine model,which may be re-lated to its inhibition of phosphorylation of MAPKs/NF-κB pathway.

ObjectiveTo investigate the general situation of defect of vertebral column among primary and middle school students in Minhang District of Shanghai and analyze the related factors， to provide a scientific basis for prevention and treatment. MethodsFrom September to October 2022， a total of 5 715 students were selected from two primary schools， two middle schools， and two high schools in Minhang District for physical examinations and screening for defect of vertebral column. ResultsTotally 219 students had defect of vertebral column， accounting for 3.83% of the sampled population. Anteroposterior spinal abnormalities were found in 4 individuals， accounting for 0.07%， and 218 students had scoliosis， accounting for 3.81%. The detection rate of defect of vertebral column was higher in girls （6.27%） than that in boys （1.51%）， and higher in high school students （10.74%） than in primary school students （1.31%） and middle school students （10.97%）. Students who are mildly underweight （5.95%） and who are moderately to severely underweight （7.46%） had a higher detection rate of defect of vertebral column than those with normal weight （4.54%）， overweight （2.83%）， and obesity （1.60%）. The detection rate among students with poor vision （4.32%） was significantly higher than those with normal vision （2.24%）， with all differences statistically significant （all P<0.05）. ConclusionThe positive rate of defect of vertebral column in primary and middle school students in Minhang District， Shanghai is nearly 4%， with most cases being scoliosis. Factors such as being female， increasing age， being underweight， and poor vision are associated with a higher probability of detecting defect of vertebral column.