Synthesis of All-Benzene Multi-Macrocyclic Nanocarbons via Post-Functionalization of meta-Cycloparaphenylenes.

Expanding the diversity of multi-macrocyclic nanocarbons, particularly those with all-benzene scaffolds, represents intriguing yet challenging synthetic tasks. Complementary to the existing synthetic approaches, here we report an efficient and modular post-functionalization strategy employing iridium-catalyzed C-H borylation of the highly strained meta-cycloparaphenylenes (mCPPs) and an mCPP-derived catenane. Based on the functionalized macrocyclic synthons, a number of novel all-benzene topological structures including linear and cyclic chains, polycatenane, and pretzelane have been successfully prepared and characterized, thereby showcasing the synthetic utility and potential of the post-functionalization strategy.

Relationship between increased maternal serum free human chorionic gonadotropin levels in the second trimester and adverse pregnancy outcomes: a retrospective cohort study.

BACKGROUND: A retrospective cohort study was conducted to collect the data of pregnant women who received hospital delivery in Hangzhou Women's Hospital from January 2018 to December 2020, and who participated in the second trimester (15-20+6 weeks) of free beta human chorionic gonadotropin (free ß-hCG). And the study was conducted to explore the relationship between maternal serum free ß-hCG and adverse pregnancy outcomes (APO). METHODS: We retrospectively analyzed the clinical data of 1,978 women in the elevated maternal serum free ß-hCG group (free ß-hCG ≥ 2.50 multiples of the median, MoM) and 20,767 women in the normal group (0.25 MoM ≤ free ß-hCG < 2.50 MoM) from a total of 22,745 singleton pregnancies, and modified Poisson regression analysis was used to calculate risk ratios (RRs) and 95% confidence intervals (CI) of the two groups. RESULTS: The gravidity and parity in the elevated free ß-hCG group were lower, and the differences between the groups were statistically significant (all, P < 0.05). The risks of polyhydramnios, preeclampsia, and hyperlipidemia, were increased in women with elevated free ß-hCG levels (RRs: 1.996, 95% CI: 1.322-3.014; 1.469, 95% CI: 1.130-1.911 and 1.257, 95% CI: 1.029-1.535, respectively, all P < 0.05), intrauterine growth restriction (IUGR) and female infants were also likely to happen (RRs = 1.641, 95% CI: 1.103-2.443 and 1.101, 95% CI: 1.011-1.198, both P < 0.05). Additionally, there was an association between elevated AFP and free ß-hCG levels in second-trimester (RR = 1.211, 95% CI: 1.121-1.307, P < 0.001). CONCLUSIONS: APOs, such as polyhydramnios, preeclampsia, and hyperlipidemia, were increased risks of elevated free ß-hCG levels, IUGR and female infants were also likely to happen. Furthermore, there was an association between elevated AFP levels and elevated free ß-hCG levels in second-trimester. We recommend prenatal monitoring according to the elevated maternal serum free ß-hCG level and the occurrence of APO.

Polymorphisms of HLA genes and hypersensitivity to penicillin among patients in a Taiwanese population.

Penicillin allergy is a potentially life-threatening condition that is common among patients. However, the genetic associations with penicillin allergy are not yet recognized for prevention or diagnosis, particularly in East Asian populations. We conducted a retrospective case-control study using data from the Taiwan Precision Medicine Initiative and analysing DNA samples to identify eight major MHC Class I and Class II loci. We employed imputation methods for accurate HLA typing and enrolled 17,827 individuals who received penicillin. Logistic regression analyses were utilized to explore associations between HLA genotypes, comorbidities and allergy risk, while simultaneously conducting a subgroup analysis to explore the association between HLA genotypes, comorbidities and the severity of allergic reactions. Our study assigned 496 cases to the penicillin allergy group and 4960 controls to a matched group. The risk of penicillin allergy was significantly higher with HLA-DPB1*05:01 (OR = 1.36, p = .004) and HLA-DQB1*05:01 (OR = 1.54, p = .03), with adjusted p-values of .032 and .24, respectively. Urticaria was identified as a separate risk factor (OR = 1.73, p < .001). However, neither the HLA alleles nor the comorbidities had a significant relationship with the risk of severe penicillin-induced allergy. HLA-DPB1*05:01 was found to be significantly associated with penicillin allergy reactions among the Taiwanese population.

Perinatal factors and early neonatal outcomes of abnormal birthweight infants in Hangzhou, China, 2015-2021: a retrospective cohort study.

BACKGROUND: This study aimed to investigate the perinatal factors and early neonatal outcomes of abnormal birth weight (ABW) in Hangzhou, China from 2015 to 2021. METHODS: A retrospective cohort study was designed to analyse the data of 76 847 newborns, in which the case groups included 3042 cases of low birth weight (LBW) and 2941 cases of fetal macrosomia (MAC), and 70 864 cases of normal weight were as the reference group. RESULTS: The incidence of LBW and MAC was 3.96% and 3.83% in Hangzhou, China from 2015 to 2021. Prematurity (<37 weeks), multiple births, hospitalisation >7 days, fetal anomalies, caesarean section, pregnancy complications, maternal coinfection with pathogens and summer births would be correlated with the incidence of LBW (ORs=43.50, 7.60, 2.09, 1.89, 1.57, 1.28, 1.19 and 1.18, all p<0.05). Factors such as post-term pregnancy (>41 weeks), scarred uterus, anterior vaginal incision and gravidity ≥2 were correlated with decreased incidence of LBW, with ORs of 0.05, 0.54, 0.65 and 0.80. Moreover, caesarean delivery, post-term pregnancy (> 41 weeks), parity ≥1, lateral vaginal incision, gravidity ≥2, hospitalisation >7 days, winter births and pregnancy complications also have association with the incidence of MAC (ORs=3.92, 2.73, 2.19, 1.87, 1.22, 1.20, 1.17 and 1.13, all p<0.05) while prematurity (<37 weeks), scarred uterus and anterior vaginal incision have close association with decreased incidence of MAC, with ORs of 0.07, 0.21 and 0.74 (all p<0.05). CONCLUSION: There was a trend of yearly increase in ABW in Hangzhou, China from 2015 to 2021. Several neonatal and maternal-related variables such as caesarean section, pregnancy complications and hospitalisation >7 days are associated with the odds of LBW and MAC, however, factors such as pregnancy with scarred uterus relate to the decrease of ABW. Close monitoring and intervention during pregnancy are essential to reduce the occurrence of ABW.

Characterization and epidemiologic analysis of mycoplasmal pneumonia of sheep in Qinghai Province.

Mycoplasmal pneumonia in sheep and goats usually result covert but huge economic losses in the sheep and goat industry. The disease is prevalent in various countries in Africa and Asia. Clinical manifestations in affected animals include anorexia, fever, and respiratory symptoms such as dyspnea, polypnea, cough, and nasal discharge. Due to similarities with other respiratory infections, accurate diagnosis can be challenging, and isolating the causative organism is often problematic. However, the utilization of molecular techniques, such as PCR, allows for rapid and specific identification of pathogens. Thus, a goat infection model with Mycoplasma was established and the pathogen was tested using PCR. The results indicated that this approach could be effectively utilized for the rapid detection of mycoplasma in clinical settings. Additionally, the prevalence of contagious pleuropneumonia of sheep in Qinghai Province was further investigated through PCR analysis. A total of 340 nasal swabs were collected from 17 sheep farms in Qinghai province. Among these samples, 84 tested positive for Mycoplasma mycoides subsp. capri (Mmc) and 148 tested positive for Mycoplasma ovipneumoniae (Movi), resulting in positive rates of 24.71% and 43.53% respectively. Furthermore, our investigation revealed positive PCR results for nasal swabs, trachea, and lung samples obtained from sheep exhibiting symptoms suggestive of mycoplasma infection. Moreover, three distinct strains were isolated from these positive samples. Additionally, the inflammatory cytokines of peripheral blood mononuclear cells (PBMCs) were assessed using RT-PCR. The findings demonstrated a high susceptibility of sheep to Movi in Qinghai province, with infected sheep displaying an inflammatory response. Consequently, the outcomes of this study will furnish valuable epidemiological insights for the effective prevention and control of this disease within Qinghai Province.

The effect of PDK1 in maintaining immune cell development and function.

3-phosphoinositide-dependent protein kinase 1 (PDK1) exhibits a substantial influence on immune cell development by establishing a vital connection between PI3K and downstream mTOR signaling cascades. However, it remains unclear whether PDK1 signaling affects the homeostasis and functionality of immune cells. To explore the impact of PDK1 on different immune cells within immune organs, transgenic mouse strains with lymphocyte-specific PDK1 knockout (PDK1fl/fl CD2-Cre) were generated. Unlike wild-type (WT) mice, lymphocyte-specific PDK1 knockout (KO) mice exhibited thymic atrophy, elevated percentages of CD8+ T cells and neutrophils, and reduced proportions of γδ T cells, B cells, and NK cells in the spleen. Functional analysis revealed elevated release of IFN-γ and IL-17A by T cells in PDK1 KO mice, contrasting with diminished levels observed in γδ T cells and Treg cells. Furthermore, the activation, cytotoxicity, and migratory potential of γδ T cells in PDK1 KO mice are heightened, indicating a potential association with the regulation of the mTOR signaling pathway. To conclude, the findings of this research demonstrated that specific knockout of PDK1 in lymphocytes hindered T cell development in the thymus and exhibited a substantial influence on immune cell homeostasis in the spleen and lymph nodes.

Association of the Reduced Levels of Monocyte Chemoattractant Protein-1 with Herpes Zoster in Rheumatoid Arthritis Patients Treated with Janus Kinase Inhibitors in a Single-Center Cohort.

Anti-interferon (IFN)-γ autoantibodies are linked to varicella zoster virus (VZV) infection. Given the elevated risks of herpes zoster (HZ) in rheumatoid arthritis (RA) patients treated with Janus kinase inhibitors (JAKis), we aimed to examine the relationship between anti-IFN-γ autoantibodies with HZ development in JAKi-treated patients. Serum titers of anti-IFN-γ autoantibodies, plasma levels of IFN-γ, monocyte chemoattractant protein-1 (MCP-1), and IFN-γ-inducible protein-10 (IP-10) were measured by ELISA. Among the 66 enrolled RA patients, 24 developed new-onset HZ. Significantly lower MCP-1 levels were observed in patients with HZ compared to those without (median, 98.21 pg/mL, interquartile range (IQR) 77.63-150.30 pg/mL versus 142.3 pg/mL, IQR 106.7-175.6 pg/mL, p < 0.05). There was no significant difference in anti-IFN-γ titers, IFN-γ levels, or IP-10 levels between patients with and without HZ. Three of 24 patients with HZ had severe HZ with multi-dermatomal involvement. Anti-IFN-γ titers were significantly higher in patients with severe HZ than in those with non-severe HZ (median 24.8 ng/mL, IQR 21.0-38.2 ng/mL versus 10.5 ng/mL, IQR 9.9-15.0 ng/mL, p < 0.005). Our results suggest an association between reduced MCP-1 levels and HZ development in JAKi-treated RA patients. High-titer anti-IFN-γ autoantibodies may be related to severe HZ in these patients.

Head and Neck Osteosarcoma: Perineural Invasion is Associated With Disease-Free Survival and Tumor Metastasis.

BACKGROUND: Head and neck osteosarcoma (HNOS) is the most common bone malignancy in the head and neck region, accounting for 10% of all osteosarcoma cases. Perineural invasion (PNI) is a notable indication of aggressive tumor behavior, which includes the phenomenon of tumor cells invading any of the 3 layers of the nerve sheath or tumor cells gathering, encircling one-third of the nerve circumference, and infiltrating and metastasizing along the nerve. PNI has been reported in various malignant tumors and is considered to be linked to poor prognosis. PURPOSE: The study's purpose is to measure the association between PNI and survival outcomes in patients with HNOS. STUDY DESIGN, SETTING, SAMPLE: This retrospective cohort study focused on HNOS patients who underwent surgery at the Department of Oral and Maxillofacial Head and Neck Oncology, Shanghai Ninth People's Hospital School of Medicine, Shanghai Jiao Tong University, from January 1, 2019 to December 31, 2021. Patients who did not undergo complete surgical resection of the tumor, did not receive a conventional osteosarcoma diagnosis, and had positive surgical margins were eliminated. PREDICTOR VARIABLE: The predictor variable is PNI status. The pathological section of the tumor was consistent with any of the PNI features, which was considered PNI-positive. MAIN OUTCOME VARIABLE(S): The primary outcome variables were 3-year disease-free survival (DFS) and 3-year overall survival. Secondary outcomes were 3-year tumor local recurrence and 3-year metastasis (MT). COVARIATES: Covariates were categorized into the following categories: demographic variables (age, sex), clinical variables (tumor region, primary tumor), and treatment variables (chemotherapy, radiotherapy). ANALYSES: Analytic statistical methods were used for the data analysis. Pearson χ2 or Fisher's exact test was used to describe the baseline data. Kaplan-Meier is used to calculate survival rates. The Cox regression model was adapted for univariate and multivariate analysis. A P value less than .05 indicated statistical significance. RESULTS: The study sample comprised 70 patients; 33 (47.1%) were male, and the mean age was 42.2 (standard deviation: 16.7) years. There were 15 (21.4%) cases of PNI. The 3-year DSF rate and OS rate were 67.3% and 82.0%, respectively. PNI-positive resulted in higher risk for MT (P ＜ .01, hazard ratio: 5.95, 95% confidence interval: 1.62-21.86) and negative impact on DFS (P < .01, hazard ratio: 6.35, 95% confidence interval: 2.11-19.17) for HNOS patients. CONCLUSION AND RELEVANCE: Positive PNI status was associated with decreased DFS and increased risk of MT.

Enhancement of NETosis by ACE2-cross-reactive anti-SARS-CoV-2 RBD antibodies in patients with COVID-19.

BACKGROUND: High levels of neutrophil extracellular trap (NET) formation or NETosis and autoantibodies are related to poor prognosis and disease severity of COVID-19 patients. Human angiotensin-converting enzyme 2 (ACE2) cross-reactive anti-severe acute respiratory syndrome coronavirus 2 spike protein receptor-binding domain (SARS-CoV-2 RBD) antibodies (CR Abs) have been reported as one of the sources of anti-ACE2 autoantibodies. However, the pathological implications of CR Abs in NET formation remain unknown. METHODS: In this study, we first assessed the presence of CR Abs in the sera of COVID-19 patients with different severity by serological analysis. Sera and purified IgG from CR Abs positive COVID-19 patients as well as a mouse monoclonal Ab (mAb 127) that can recognize both ACE2 and the RBD were tested for their influence on NETosis and the possible mechanisms involved were studied. RESULTS: An association between CR Abs levels and the severity of COVID-19 in 120 patients was found. The CR Abs-positive sera and IgG from severe COVID-19 patients and mAb 127 significantly activated human leukocytes and triggered NETosis, in the presence of RBD. This NETosis, triggered by the coexistence of CR Abs and RBD, activated thrombus-related cells but was abolished when the interaction between CR Abs and ACE2 or Fc receptors was disrupted. We also revealed that CR Abs-induced NETosis was suppressed in the presence of recombinant ACE2 or the Src family kinase inhibitor, dasatinib. Furthermore, we found that COVID-19 vaccination not only reduced COVID-19 severity but also prevented the production of CR Abs after SARS-CoV-2 infection. CONCLUSIONS: Our findings provide possible pathogenic effects of CR Abs in exacerbating COVID-19 by enhancing NETosis, highlighting ACE2 and dasatinib as potential treatments, and supporting the benefit of vaccination in reducing disease severity and CR Abs production in COVID-19 patients.

Measurement of the Earth Tides with a Diamagnetic-Levitated Micro-Oscillator at Room Temperature.

The precise measurement of the gravity of Earth plays a pivotal role in various fundamental research and application fields. Although a few gravimeters have been reported to achieve this goal, miniaturization of high-precision gravimetry remains a challenge. In this work, we have proposed and demonstrated a miniaturized gravimetry operating at room temperature based on a diamagnetic levitated micro-oscillator with a proof mass of only 215 mg. Compared with the latest reported miniaturized gravimeters based on microelectromechanical systems, the performance of our gravimetry has substantial improvements in that an acceleration sensitivity of 15 µGal/sqrt[Hz] and a drift as low as 61 µGal per day have been reached. Based on this diamagnetic levitation gravimetry, we observed Earth tides, and the correlation coefficient between the experimental data and theoretical data reached 0.97. Some moderate foreseeable improvements can develop this diamagnetic levitation gravimetry into a chip size device, making it suitable for mobile platforms such as drones. Our advancement in gravimetry is expected to facilitate a multitude of applications, including underground density surveying and the forecasting of natural hazards.

Validation of the PediBIRN-7 clinical prediction rule for pediatric abusive head trauma.

BACKGROUND: The PediBIRN-7 clinical prediction rule incorporates the (positive or negative) predictive contributions of completed abuse evaluations to estimate abusive head trauma (AHT) probability after abuse evaluation. Applying definitional criteria as proxies for AHT and non-AHT ground truth, it performed with sensitivity 0.73 (95 % CI: 0.66-0.79), specificity 0.87 (95 % CI: 0.82-0.90), and ROC-AUC 0.88 (95 % CI: 0.85-0.92) in its derivation study. OBJECTIVE: To validate the PediBIRN-7's AHT prediction performance in a novel, equivalent, patient population. PARTICIPANTS AND SETTINGS: Consecutive, acutely head-injured children <3 years hospitalized for intensive care across eight sites between 2017 and 2020 with completed skeletal surveys and retinal exams (N = 342). METHODS: Secondary analysis of an existing, cross-sectional, prospective dataset, including assignment of patient-specific estimates of AHT probability, calculation of AHT prediction performance measures (ROC-AUC, sensitivity, specificity, predictive values), and completion of sensitivity analyses to estimate best- and worst-case prediction performances. RESULTS: Applying the same definitional criteria, the PediBIRN-7 performed with sensitivity 0.74 (95 % CI: 0.66-0.81), specificity 0.77 (95 % CI: 0.70-0.83), and ROC-AUC 0.83 (95 % CI: 0.78-0.88). The reduction in ROC-AUC was statistically insignificant (p = .07). Applying physicians' final consensus diagnoses as proxies for AHT and non-AHT ground truth, the PediBIRN-7 performed with sensitivity 0.73 (95 % CI: 0.66-0.79), specificity 0.87 (95 % CI: 0.82-0.90), and ROC-AUC 0.90 (95 % CI: 0.87-0.94). Sensitivity analyses demonstrated minimal changes in rule performance. CONCLUSION: The PediBIRN-7's overall AHT prediction performance has been validated in a novel, equivalent, patient population. Its patient-specific estimates of AHT probability can inform physicians' AHT-related diagnostic reasoning after abuse evaluation.

UHRF1P contributes to IL-17A-mediated systemic lupus erythematosus via UHRF1-MAP4K3 axis.

Inflammatory T cells contribute to the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). Analysis of the T-cell transcriptomics data of two independent SLE patient cohorts by three machine learning models revealed the pseudogene UHRF1P as a novel SLE biomarker. The pseudogene-encoded UHRF1P protein was overexpressed in peripheral blood T cells of SLE patients. The UHRF1P protein lacks the amino-terminus of its parental UHRF1 protein, resulting in missing the proteasome-binding ubiquitin-like (Ubl) domain of UHRF1. T-cell-specific UHRF1P transgenic mice manifested the induction of IL-17A and autoimmune inflammation. Mechanistically, UHFR1P prevented UHRF1-induced Lys48-linked ubiquitination and degradation of MAP4K3 (GLK), which is a kinase known to induce IL-17A. Consistently, IL-17A induction and autoimmune phenotypes of UHRF1P transgenic mice were obliterated by MAP4K3 knockout. Collectively, UHRF1P overexpression in T cells inhibits the E3 ligase function of its parental UHRF1 and induces autoimmune diseases.

The characterization and comorbidities of heterozygous Bardet-Biedl syndrome carriers.

Introduction: Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder with clinical features of retinal dystrophy, obesity, postaxial polydactyly, renal anomalies, learning disabilities, hypogonadism, and genitourinary abnormalities. Nevertheless, previous studies on the phenotypic traits of BBS heterozygous carriers have generated inconclusive results. The aim of our study was to investigate the impact of BBS heterozygosity on carriers when compared to non-carriers within the Taiwanese population. Materials and Methods: This study follows a hospital-based case-control design. We employed the Taiwan Biobank version 2 (TWBv2) array to identify three specific loci associated with BBS (rs773862084, rs567573386, and rs199910690). In total, 716 patients were included in the case group, and they were compared to a control group of 2,864 patients who lacked BBS alleles. The control group was selected through gender and age matching at a ratio of 1:4. The association between BBS-related loci and comorbidity was assessed using logistic regression models. Results: We found that BBS heterozygous carriers exhibited a significant association with elevated BMI levels, especially the variant rs199910690 in MKS1 (p=0.0037). The prevalence of comorbidities in the carriers' group was not higher than that in the non-carriers' group. Besides, the average values of the biochemistry data showed no significant differences, except for creatinine level. Furthermore, we conducted a BMI-based analysis to identify specific risk factors for chronic kidney disease (CKD). Our findings revealed that individuals carrying the CA/AA genotype of the BBS2 rs773862084 variant or the CT/TT genotype of the MKS1 rs199910690 variant showed a reduced risk of developing CKD, irrespective of their BMI levels. When stratified by BMI level, obese males with the MKS1 rs199910690 variant and obese females with the BBS2 rs773862084 variant exhibited a negative association with CKD development. Conclusion: We found that aside from the association with overweight and obesity, heterozygous BBS mutations did not appear to increase the predisposition of individuals to comorbidities and metabolic diseases. To gain a more comprehensive understanding of the genetic susceptibility associated with Bardet-Biedl Syndrome (BBS), further research is warranted.

Polygenic Risk Score Predicts Earlier-Onset Adult Systemic Lupus Erythematosus and First-Year Renal Diseases in a Taiwanese Cohort.

OBJECTIVES: This study aimed to develop a predictive model using polygenic risk score (PRS) to forecast renal outcomes for adult systemic lupus erythematosus (SLE) in a Taiwanese population. METHODS: Patients with SLE (n=2782) and matched non-SLE controls (n=11 128) were genotyped using Genome-Wide TWB 2.0 single-nucleotide polymorphism (SNP) array. PRS models (C+T, LDpred2, Lassosum, PRSice-2, PRS-continuous shrinkage (CS)) were constructed for predicting SLE susceptibility. Logistic regression was assessed for C+T-based PRS association with renal involvement in patients with SLE. RESULTS: In the training set, C+T-based SLE-PRS, only incorporating 27 SNPs, outperformed other models with area under the curve (AUC) values of 0.629, surpassing Lassosum (AUC=0.621), PRSice-2 (AUC=0.615), LDpred2 (AUC=0.609) and PRS-CS (AUC=0.602). Additionally, C+T-based SLE-PRS demonstrated consistent predictive capacity in the testing set (AUC=0.620). Individuals in the highest quartile exhibited earlier SLE onset (39.06 vs 44.22 years, p<0.01), higher Systemic Lupus Erythematosus Disease Activity Index scores (3.00 vs 2.37, p=0.04), elevated risks of renal involvement within the first year of SLE diagnosis, including WHO class III-IV lupus nephritis (OR 2.36, 95% CI 1.47 to 3.80, p<0.01), estimated glomerular filtration rate <60 mL/min/1.73m2 (OR 1.49, 95% CI 1.18 to 1.89, p<0.01) and urine protein-to-creatinine ratio >150 mg/day (OR 2.07, 95% CI 1.49 to 2.89, p<0.01), along with increased seropositivity risks, compared with those in the lowest quartile. Furthermore, among patients with SLE with onset before 50 years, the highest PRS quartile was significantly associated with more serious renal diseases within the first year of SLE diagnosis. CONCLUSIONS: PRS of SLE is associated with earlier onset, renal involvement within the first year of SLE diagnosis and seropositivity in Taiwanese patients. Integrating PRS with clinical decision-making may enhance lupus nephritis screening and early treatment to improve renal outcomes in patients with SLE.

Insights into ThB40: Stability, Electronic Structure, and Interaction.

The interaction between nonmetal and metal atoms has attracted great interest in the development of organometallic compounds and their promising applications. In this study, we explored the interaction between boron and thorium atoms, based on the stable B40Th coordination compound, by employing density functional theory calculations. We elucidated the stability and geometries of the B40Th coordination compound and revealed the electron transfer from the metal atom Th to B40, which is evidenced by the natural bond orbital calculations. This electron transfer is attributed to the electron-withdrawing character of the boron atom and results in clear electrostatic interaction. Additionally, bond critical analysis and bond order calculations show obvious covalent characters between the metal and nonmetal atoms. The IR spectrum was simulated to give detailed information to identify this targeted compound in future experiments. This study is expected to enhance the understanding of metal-nonmetal interactions and provides useful information for constructing new organometallic compounds based on actinium metal atoms.

Impaired health-related quality of life in idiopathic inflammatory myopathies: a cross-sectional analysis from the COVAD-2 e-survey.

Objectives: To investigate health-related quality of life in patients with idiopathic inflammatory myopathies (IIMs) compared with those with non-IIM autoimmune rheumatic diseases (AIRDs), non-rheumatic autoimmune diseases (nrAIDs) and without autoimmune diseases (controls) using Patient-Reported Outcome Measurement Information System (PROMIS) instrument data obtained from the second COVID-19 vaccination in autoimmune disease (COVAD-2) e-survey database. Methods: Demographics, diagnosis, comorbidities, disease activity, treatments and PROMIS instrument data were analysed. Primary outcomes were PROMIS Global Physical Health (GPH) and Global Mental Health (GMH) scores. Factors affecting GPH and GMH scores in IIMs were identified using multivariable regression analysis. Results: We analysed responses from 1582 IIM, 4700 non-IIM AIRD and 545 nrAID patients and 3675 controls gathered through 23 May 2022. The median GPH scores were the lowest in IIM and non-IIM AIRD patients {13 [interquartile range (IQR) 10-15] IIMs vs 13 [11-15] non-IIM AIRDs vs 15 [13-17] nrAIDs vs 17 [15-18] controls, P < 0.001}. The median GMH scores in IIM patients were also significantly lower compared with those without autoimmune diseases [13 (IQR 10-15) IIMs vs 15 (13-17) controls, P < 0.001]. Inclusion body myositis, comorbidities, active disease and glucocorticoid use were the determinants of lower GPH scores, whereas overlap myositis, interstitial lung disease, depression, active disease, lower PROMIS Physical Function 10a and higher PROMIS Fatigue 4a scores were associated with lower GMH scores in IIM patients. Conclusion: Both physical and mental health are significantly impaired in IIM patients, particularly in those with comorbidities and increased fatigue, emphasizing the importance of patient-reported experiences and optimized multidisciplinary care to enhance well-being in people with IIMs.

Vertical migration behavior simulation and prediction of Pb and Cd in co-contaminated soil around Pb-Zn smelting slag site.

Heavy metal migration in soil poses a serious threat to the soil and groundwater. Understanding the migration pattern of heavy metals (HMs) under different factors could provide a more reasonable position for pollution evaluation and targetoriented treatment of soil heavy metal. In this study, the migration behavior of Pb and Cd in co-contaminated soil under different pH and ionic strength (NaCl concentration) was simulated using convective dispersion equation (CDE). We predicted the migration trends of Pb and Cd in soils after 5, 10, and 20 years via PHREEQC. The results showed that the migration time of Cd in the soil column experiment was about 60 days faster than that of Pb, and the migration trend was much steeper. The CDE was proved to describe the migration behavior of Pb and Cd (R2 > 0.75) in soil. The predicted results showed that Cd migrated to 15-20 cm of soil within 7 years and Pb stayed mainly in the top 0-6 cm of soil within 5 years as the duration of irrigation increased. Overall, our study is expected to provide new insight into the migration of heavy metal in soil ecosystems and guidance for reducing risk of heavy metal in the environment.

L-Type Calcium Channel Modulates Low-Intensity Pulsed Ultrasound-Induced Excitation in Cultured Hippocampal Neurons.

As a noninvasive technique, ultrasound stimulation is known to modulate neuronal activity both in vitro and in vivo. The latest explanation of this phenomenon is that the acoustic wave can activate the ion channels and further impact the electrophysiological properties of targeted neurons. However, the underlying mechanism of low-intensity pulsed ultrasound (LIPUS)-induced neuro-modulation effects is still unclear. Here, we characterize the excitatory effects of LIPUS on spontaneous activity and the intracellular Ca2+ homeostasis in cultured hippocampal neurons. By whole-cell patch clamp recording, we found that 15 min of 1-MHz LIPUS boosts the frequency of both spontaneous action potentials and spontaneous excitatory synaptic currents (sEPSCs) and also increases the amplitude of sEPSCs in hippocampal neurons. This phenomenon lasts for > 10 min after LIPUS exposure. Together with Ca2+ imaging, we clarified that LIPUS increases the [Ca2+]cyto level by facilitating L-type Ca2+ channels (LTCCs). In addition, due to the [Ca2+]cyto elevation by LIPUS exposure, the Ca2+-dependent CaMKII-CREB pathway can be activated within 30 min to further regulate the gene transcription and protein expression. Our work suggests that LIPUS regulates neuronal activity in a Ca2+-dependent manner via LTCCs. This may also explain the multi-activation effects of LIPUS beyond neurons. LIPUS stimulation potentiates spontaneous neuronal activity by increasing Ca2+ influx.

Ferried Albumin-Inspired Bioadhesive With Dynamic Interfacial Bonds for Emergency Rescue.

Emergency prehospital wound closure and hemorrhage control are the first priorities for life-saving. Majority of bioadhesives form bonds with tissues through irreversible cross-linking, and the remobilization of misalignment may cause severe secondary damage to tissues. Therefore, developing an adhesive that can quickly and tolerably adhere to traumatized dynamic tissue or organ surfaces in emergency situations is a major challenge. Inspired by the structure of human serum albumin (HSA), a branched polymer with multitentacled sulfhydryl is synthesized, then, an instant and fault-tolerant tough wet-tissue adhesion (IFA) hydrogel is prepared. Adhesive application time is just 5 s (interfacial toughness of ≈580 J m-2), and favorable tissue-adhesion is maintained after ten cycles. IFA hydrogel shows unchangeable adhesive performance after 1 month of storage based on the internal oxidation-reduction mechanism. It not only can efficiently seal various organs but also achieves effective hemostasis in models of the rat femoral artery and rabbit-ear artery. This work also proposes an effective strategy for controllable adhesion, enabling the production of asymmetric adhesives with on-demand detachment. Importantly, IFA hydrogel has sound antioxidation, antibacterial property, hemocompatibility, and cytocompatibility. Hence, the HSA-inspired bioadhesive emerges as a promising first-aid supply for human-machine interface-based health management and non-invasive wound closure.