Longitudinal trajectories of disability among Chinese adults: the role of cardiometabolic multimorbidity.

BACKGROUND: Cardiometabolic multimorbidity (CM) has been found to be associated with higher mortality and functional limitations. However, few studies have investigated the longitudinal association between CM and disability in the Chinese population and whether these associations vary by smoking status. METHODS: The study included 16,754 participants from four waves (2011, 2013, 2015, and 2018) of China Health and Retirement Longitudinal Study (CHARLS) (mean age: 59, female: 51%). CM was assesed at baseline and defined as having two or more of diabetes, stroke, or heart disease. Disability was repeatedly measured by summing the number of impaired activities of daily living (ADL) and instrumental activities of daily living (IADL) during the 7-year follow-up. Linear mixed-effects model was used to determine the association of CM and trajectories of disability and to assess the modification effect of smoking status in these associations. RESULTS: Participants with CM at baseline had a faster progression of disability compared to those without CM (CM: ß = 0.13, 95% CI: 0.05 to 0.21). Current smokers with CM developed disability faster than their counterparts (Pinteraction for smoking=0.011). In addition, there was a significant association between CM and the annual change of disability in current smokers (ß = 0.34, 95% CI: 0.17 to 0.50) while no such association was observed in current non-smokers (ß = 0.08, 95% CI: -0.02 to 0.17). CONCLUSION: CM was associated with more a rapid disability progression. Notably, being current smokers may amplify the adverse effects of CM on disability progression.

Imaging diagnosis and efficacy monitoring by [89Zr]Zr-DFO-KN035 immunoPET in patients with PD-L1-positive solid malignancies.

Rationale: Although programmed death-ligand 1 (PD-L1) inhibitors have achieved efficacy in cancer therapy, their response rate is low. Differences in the prognosis of patients with cancer under anti-PD-L1 treatment are related to the PD-L1 level in tumors. Accurate PD-L1 detection can optimize the accuracy of tumor immunotherapy and avoid ineffective clinical diagnosis and treatments. Methods: We investigated the imaging efficiency and therapy monitoring capacity of [89Zr]Zr-DFO-KN035 immunoPET for tumors. We labeled the monodomain anti-PD-L1 antibody KN035 with the radionuclide zirconium-89 and used this tracer for PET imaging. [89Zr]Zr-DFO-KN035 uptakes in patients with PD-L1-positive tumors, including primary and metastatic tumors, as well as in normal tissues, were comparatively assessed by using positron emission tomography/computed tomography imaging. Results: In PD-L1-positive patients, [89Zr]Zr-DFO-KN035 was sensitive in tumor-targeting imaging and could detect multiple metastatic foci, including multiple bone metastases (tumor-to-muscle ratios of 7.102 and 6.118 at 55 and 120 h, respectively) and lymph-node metastases (tumor-to-muscle ratios of 11.346 and 6.542 at 55 and 120 h, respectively). The needed radioactive dose of [89Zr]Zr-DFO-KN035 (55.5-92.5 MBq) used in this study was considerably lower than that of [18F]FDG (370-555 MBq). [89Zr]Zr-DFO-KN035 monitored and predicted the site of adverse reactions in antitumor immunotherapy. Moreover, after antitumor treatment, [89Zr]Zr-DFO-KN035 enabled observational imaging for therapeutic efficacy evaluation, which can help predict patient prognosis. Conclusion: [89Zr]Zr-DFO-KN035 can be used for the diagnosis and therapy monitoring of PD-L1-positive tumors and provide noninvasive and comprehensive observations for tumor diagnostic imaging, prognosis prediction, and efficacy evaluation.

Near-room temperature ferromagnetism and a tunable anomalous Hall effect in atomically thin Fe4CoGeTe2.

Itinerant ferromagnetism at room temperature is a key factor for spin transport and manipulation. Here, we report the realization of near-room temperature itinerant ferromagnetism in Co doped Fe5GeTe2 thin flakes. The ferromagnetic transition temperature TC (∼323 K-337 K) is almost unchanged when the thickness is as low as 12 nm and is still about 284 K at 2 nm (bilayer thickness). Theoretical calculations further indicate that the ferromagnetism persists in monolayer Fe4CoGeTe2. In addition to the robust ferromagnetism down to the ultrathin limit, Fe4CoGeTe2 exhibits an unusual temperature- and thickness-dependent intrinsic anomalous Hall effect. We propose that it could be ascribed to the dependence of the band structure on thickness that changes the Berry curvature near the Fermi energy level subtly. The near-room temperature ferromagnetism and tunable anomalous Hall effect in atomically thin Fe4CoGeTe2 provide opportunities to understand the exotic transport properties of two-dimensional van der Waals magnetic materials and explore their potential applications in spintronics.

A novel PSMA targeted dual-function near-infrared fluorescence and PET probe for the image-guided surgery and detection of prostate cancer.

PURPOSE: Prostate-specific membrane antigen (PSMA) is a promising diagnostic biomarker for prostate cancer (PCa). NYM016, a novel small-molecule PSMA-targeted fluorescence probe for the surgical navigation of PCa, was designed in this work. Furthermore, the potential of the PET agent [68Ga]Ga-NYM016 for the radionuclide imaging of PCa was evaluated. METHODS: NYM016 was designed with the near-infrared fluorescent group Cyanine 7 (Cy7) and the chelating group NOTA. The radioactive probe [68Ga]Ga-NYM016 was designed and synthesized on the basis of NYM016. The abovementioned probes were assessed in PSMA-positive xenograft-bearing models and patients diagnosed with PCa. RESULTS: NYM016 obviously aggregated in the tumor site of the mouse model, and its fluorescence intensity was stable within 24 h. NYM016 was well-tolerated, and no adverse events were found in the clinical study. Moreover, it was also observed in the excised lesions from the patient with PCa, and its fluorescence aggregated at the same site where PSMA was highly expressed. In addition, the PSMA xenograft demonstrated intense [68Ga]Ga-NYM016 uptake at 2.5 min after injection. At 3 h after injection, [68Ga]Ga-NYM016 uptake by the PSMA xenograft gradually increased to 6.40 ± 0.19%ID/g, which was higher that by the blocked and negative groups (2.28 ± 0.07%ID/g, P < 0.05; 2.28 ± 0.22%ID/g, P < 0.05). In the clinical study, [68Ga]Ga-NYM016 was well-tolerated and no adverse events were observed. Substantial accumulation was observed in primary and metastatic lesions in a patient with recurrence with the maximum standardized uptake value of 18.93. Meanwhile, negative [68Ga]Ga-NYM016 uptake was observed at the prostate site of a patient with prostatitis. CONCLUSION: The novel fluorescence probe NYM016 and the radioactive tracer [68Ga]Ga-NYM016 are promising candidates for the surgical navigation and radionuclide imaging of PCa, respectively. TRIAL REGISTRATION: The clinical evaluation of this study was registered at Clinicaltrial.gov (NCT05623878) on 21 Dec, 2022.

Exoskeleton Partial-Coated Stem Cells for Infarcted Myocardium Restoring.

The integration of abiotic materials with live cells has emerged as an exciting strategy for the control of cellular functions. Exoskeletons consisting ofmetal-organic frameworks are generated to produce partial-coated bone marrow stem cells (BMSCs) to overcome low cell survival leading to disappointing effects for cell-based cardiac therapy. Partially coated exoskeletons can promote the survival of suspended BMSCs by integrating the support of exoskeletons and unimpaired cellular properties. In addition, partial exoskeletons exhibit protective effects against detrimental environmental conditions, including reactive oxygen species, pH changes, and osmotic pressure. The partial-coated cells exhibit increased intercellular adhesion forces to aggregate and adhere, promoting cell survival and preventing cell escape during cell therapy. The exoskeletons interact with cell surface receptors integrin α5ß1, leading to augmented biological functions with profitable gene expression alteration, such as Vegfa, Cxcl12, and Adm. The partial-coated BMSCs display enhanced cell retention in infarcted myocardium through non-invasive intravenous injections. The repair of myocardial infarction has been achieved with improved cardiac function, myocardial angiogenesis, proliferation, and inhibition of cell apoptosis. This discovery advances the elucidation of potential molecular and cellular mechanisms for cell-exoskeleton interactions and benefits the rational design and manufacture of next-generation nanobiohybrids.

Yolk-Shell and Hollow Zr/Ce-UiO-66 for Manipulating Selectivity in Tandem Reactions and Photoreactions.

One of the hallmarks of multicomponent metal-organic frameworks (MOFs) is to finely tune their active centers to achieve product selectivity. In particular, obtaining bimetallic MOF hollow structures with precisely tailored redox centers under the same topology is still challenging despite a recent surge of such efforts. Herein, we present an engineering strategy named "cluster labilization" to generate hierarchically porous MOF composites with hollow structures and tunable active centers. By partially replacing zirconium with cerium in the hexanuclear clusters of UiO-66, unevenly distributed yolk-shell structures (YSS) were formed. Through acid treatment or annealing of the YSS precursor, single-shell hollow structures (SSHS) or double-shell hollow structures (DSHS) can be obtained, respectively. The active centers in SSHS and DSHS differ in their species, valence, and spatial locations. More importantly, YSS, SSHS, and DSHS with distinct active centers and microenvironments exhibit tunable catalytic activity, reversed selectivity, and high stability in the tandem reaction and the photoreaction.

Automated Synthesis and Preclinical Evaluation of Optimized Integrin α6-Targeted Positron Emission Tomography Imaging of Pancreatic Cancer.

Integrin α6 has been considered a promising biomarker, is overexpressed in many tumors, and plays a vital role in tumor formation, recurrence, and metastasis. In this study, we identified a novel high-affinity integrin α6-targeted peptide named RD2 (Arg-Trp-Tyr-Asp-PEG4)2-Lys-Lys and developed a 18F-radiolabeled peptide tracer ([18F]-AlF-NOTA-RD2) and evaluated its potential application in positron emission tomography (PET) imaging of pancreatic cancer. [18F]-AlF-NOTA-RD2 was produced using GMP (Good Manufacturing Practice of Medical Products)-compliant automatic radiosynthesis on a single GE FASTLab2 cassette-type synthesis module. The stability of [18F]-AlF-NOTA-RD2 was analyzed in phosphate-buffered saline (PBS) and fetal bovine serum (FBS). The cell uptake assay of the tracer was assessed using PANC-1 cells. In addition, small-animal PET imaging and biodistribution studies of [18F]-AlF-NOTA-RD2 were performed in pancreatic cancer subcutaneous tumor-bearing mice. The PET tracer [18F]-AlF-NOTA-RD2 was obtained with a radiochemical yield of 23.7 ± 4.7%, radiochemical purity of >99%, and molar activity of 165.7 ± 59.1 GBq/µmol. [18F]-AlF-NOTA-RD2 exhibited good in vitro stability in PBS and FBS. LogP octanol water value for the tracer was -2.28 ± 0.05 (n = 3). The binding affinity of RD2 to the integrin α6 protein (Kd = 0.13 ± 3.65 µM, n = 3) was significantly higher than that of the RWY (CRWYDENAC) (Kd = 6.97 ± 1.44 µM, n = 3). Small-animal PET imaging and biodistribution also revealed that [18F]-AlF-NOTA-RD2 displayed rapid and good tumor uptake and lower liver background uptake in PANC-1 tumor-bearing mice. [18F]-AlF-NOTA-RD2 showed significant radioactivity accumulation in tumors and was successfully blocked by NOTA-RD2. Compared with [18F]-FDG, [18F]-AlF-NOTA-RD2 PET imaging and biodistribution studies in PANC-1 xenograft tumor-bearing mice confirmed a good tumor-to-muscle ratio (8.69 ± 2.03 vs 1.41 ± 0.23, respectively) at 0.5 h and (2.99 ± 3.02 vs 1.43 ± 0.17, respectively) at 1 h post injection. Autoradiography of human pancreatic cancer tumor tissues further confirmed high accumulation of [18F]-AlF-NOTA-RD2. In summary, we developed an optimized integrin α6-targeted imaging tracer and obtained high radioactivity products with a cassette-type synthesis module; moreover, the tracer exhibited good binding affinity with integrin α6 and good target specificity for PANC-1 cells in xenograft pancreatic tumor-bearing mice, demonstrating its promising application as a noninvasive PET radiotracer of integrin α6 expression in pancreatic cancer.

Injectable rBMSCs-laden hydrogel microspheres loaded with naringin for osteomyelitis treatment.

Osteomyelitis, caused by purulent bacteria invading bone tissue, often occurs in long bones and seriously affects the physical and mental health and working ability of patients; it can even endanger life. However, due to bone cavity structure, osteomyelitis tends to occur inside the bone and thus lacks an effective treatment; anti-inflammatory treatment and repair of bone defects are necessary. Here, we developed injectable hydrogel microspheres loaded with naringin and bone marrow mesenchymal stem cells, which have anti-inflammatory and osteogenic properties. These homogeneous microspheres, ranging from 200 to 1000µm, can be rapidly fabricated using an electro-assisted bio-fabrication method. Interestingly, it was found that microspheres with relatively small diameters (200µm) were more conducive to the initial cell attachment, growth, spread, and later osteogenic differentiation. The developed microspheres can effectively treat tibial osteomyelitis in rats within six weeks, proving their prospects for clinical application.

Synergistic effect of collagen cross-linking and remineralization for improving resin-dentin bond durability.

In this study, the synergistic effect of glutaraldehyde-cross-linking and remineralization on the strength and durability of resin-dentin bonds was investigated. Dentin surfaces were etched with 35% phosphoric acid. The control specimens were bonded with Adper Single Bond 2 using wet bonding without pretreatment. The experimental specimens were pretreated with 5% (v/v) glutaraldehyde solution for 3 min and placed in a remineralizing solution for 0, 12, and 24 h, followed by dry bonding. After performing composite build-ups on the specimens, they were longitudinally sectioned, immediately, and after aging for 3 h with sodium hypochlorite (NaOCl), to evaluate microtensile bond strength (µTBS). The cross-linked specimens exhibited µTBS values comparable with those of the control group, but the µTBS decreased significantly after NaOCl aging. The cross-linked dentin remineralized for 24 h exhibited an increase in µTBS. After aging in NaOCl, the µTBS of the specimens remineralized for 24 h did not decrease and was significantly higher than for the other experimental groups. Cross-linking with dry bonding maintained µTBS in specimens before aging in NaOCl, but the bonding durability was compromised. Remineralization of cross-linked dentin for 24 h followed by dry bonding increased the immediate µTBS and improved bond durability. Therefore, combining cross-linking with remineralization of collagen fibrils progressively increased resistance to degradation, improving bond durability.

Development of a multifunctional platform for near-infrared imaging and targeted radionuclide therapy for tumors.

Biotin receptor (BR) is overexpressed in several human tumor cell lines and has become an important biomarker for tumor diagnosis and treatment. Therefore, much attention has been attracted in the field of developing BR-targeting agents. In clinical practice, a multifunctional platform that can be used for both diagnosis and treatment is much desirable. In this study, to improve diagnostic and therapeutic efficacy of BR-positive tumors, we developed a multifunctional platform RT-H2 to combine with the cyanine scaffold for near infrared (NIR) imaging and the radioisotope 131I for targeted radionuclide therapy (TRT). In vitro experiments showed that RT-H2 possessed favorable NIR properties and could selectively accumulate in BR-positive HeLa cells. In vivo NIR imaging of HeLa tumor-bearing mice exhibited high accumulation and long retention time (72 h) of RT-H2 in the tumor. Furthermore, RT-H2 was also employed as a carrier to develop 131I-labeled TRT agent due to its favorable properties in vivo. The radiolabeling conditions were optimized and the optimal conditions determined to be 1.2 equiv of Idogen, reaction time 4 min and room temperature, yielding the radiotracer [131I]I-RT-H2 with the radiochemical purity (RCP) of > 95% after a simple purification by a C18 column. In vitro cell experiments indicated that [131I]I-RT-H2 could specifically target Hela cells and displayed dose-dependent antitumor effect. In vivo experiments demonstrated that [131I]I-RT-H2 obviously inhibited the tumor proliferation in HeLa tumor-bearing mice within 4 weeks. All these results indicate that RT-H2 has the potential to serve as a multifunctional platform for tumor diagnosis and treatment.

Sex-related differences in the hypertriglyceridemic-waist phenotype in association with hyperuricemia: a longitudinal cohort study.

BACKGROUND: There is limited longitudinal evidence supporting the association between the hypertriglyceridemic-waist (HTGW) phenotype and hyperuricemia. This study aimed to examine the longitudinal relationship between hyperuricemia and the HTGW phenotype among males and females. METHODS: A total of 5562 hyperuricemia-free participants aged 45 or over from the China Health and Retirement Longitudinal Study (mean age: 59.0) were followed for 4 years. The HTGW phenotype was defined as having elevated triglyceride levels and enlarged waist circumference (cutoffs for males: 2.0 mmol/L and 90 cm; females: 1.5 mmol/L and 85 cm). Hyperuricemia was determined by uric acid cutoffs (males: 7 mg/dl; females: 6 mg/dl. Multivariate logistic regression models were used to assess the association between the HTGW phenotype and hyperuricemia. The joint effect of the HTGW phenotype and sex on hyperuricemia was quantified, and the multiplicative interaction was assessed. RESULTS: During the four-year follow-up, 549 (9.9%) incident hyperuricemia cases were ascertained. Compared with those with normal levels of triglycerides and waist circumference, participants with the HTGW phenotype had the highest risk of hyperuricemia (OR: 2.67; 95% CI: 1.95 to 3.66), followed by an OR of 1.96 (95% CI: 1.40 to 2.74) for only higher triglyceride levels and 1.39 (95% CI: 1.03 to 1.86) for only greater waist circumference. The association between HTGW and hyperuricemia was more prominent among females (OR = 2.36; 95% CI: 1.77 to 3.15) than males (OR = 1.29; 95% CI: 0.82 to 2.04), with evidence of a multiplicative interaction (P = 0.006). CONCLUSIONS: Middle-aged and older females with the HTGW phenotype may at the highest risk of hyperuricemia. Future hyperuricemia prevention interventions should be primarily targeted for females with the HTGW phenotype.

EDB-FN targeted probes for the surgical navigation, radionuclide imaging, and therapy of thyroid cancer.

PURPOSE: Extradomain B of fibronectin (EDB-FN) is a promising diagnostic and therapeutic biomarker for thyroid cancer (TC). Here, we identified a high-affinity EDB-FN targeted peptide named EDBp (AVRTSAD) and developed three EDBp-based probes, Cy5-PEG4-EDBp(Cy5-EDBp), [18F]-NOTA-PEG4-EDBp([18F]-EDBp), and [177Lu]-DOTA-PEG4-EDBp ([177Lu]-EDBp), for the surgical navigation, radionuclide imaging, and therapy of TC. METHODS: Based on the previously identified EDB-FN targeted peptide ZD2, the optimized EDB-FN targeted peptide EDBp was identified by using the alanine scan strategy. Three EDBp-based probes, Cy5-EDBp, [18F]-EDBp, and [177Lu]-EDBp, were developed for fluorescence imaging, positron emission tomography (PET) imaging, and radiotherapy in TC tumor-bearing mice, respectively. Additionally, [18F]-EDBp was evaluated in two TC patients. RESULTS: The binding affinity of EDBp to the EDB fragment protein (Kd = 14.4 ± 1.4 nM, n = 3) was approximately 336-fold greater than that of the ZD2 (Kd = 4839.7 ± 361.7 nM, n = 3). Fluorescence imaging with Cy5-EDBp facilitated the complete removal of TC tumors. [18F]-EDBp PET imaging clearly delineated TC tumors, with high tumor uptake (16.43 ± 1.008%ID/g, n = 6, at 1-h postinjection). Radiotherapy with [177Lu]-EDBp inhibited tumor growth and prolonged survival in TC tumor-bearing mice (survival time of different treatment groups: saline vs. EDBp vs. ABRAXANE vs. [177Lu]-EDBp = 8.00 d vs. 8.00 d vs. 11.67 d vs. 22.33 d, ***p < 0.001). Importantly, the first-in-human evaluation of [18F]-EDBp demonstrated that it had specific targeting properties (SUVmax value of 3.6) and safety. CONCLUSION: Cy5-EDBp, [18F]-EDBp, and [177Lu]-EDBp are promising candidates for the surgical navigation, radionuclide imaging, and radionuclide therapy of TC, respectively.

Association between subjective cognitive complaints, balance impairment and disability among middle-aged and older adults: Evidence from a population-based cohort study.

AIM: To quantify the association between subjective cognitive complaints and balance impairment in relation to the occurrence of disability. METHODS: In total, 6885 adults aged ≥45 who participated in the China Health and Retirement Longitudinal Study (CHARLS) were followed for 7 years. Subjective cognitive complaints were evaluated by self-reported memory problems. Balance impairment was tested by side-by-side stand, semi-tandem stand and full tandem stand. Disability was measured by activities of daily living (ADL) and instrumental activities of daily living (IADL). Multivariate logistic regression models were applied to test the joint effect between baseline subjective cognitive complaints and balance impairment on disability. The multiplicative interaction was examined. RESULTS: A joint effect of experiencing both subjective cognitive complaints and balance impairment was identified, showing a 1.63-fold higher risk of ADL and IADL disability than those experienced by neither of the two (odds ratio = 1.63, 95% confidence interval: 1.36-1.95). There was evidence of multiplicative interaction (P = 0.004). CONCLUSIONS: Among middle-aged and older people, the coexistence of subjective cognitive complaints and balance impairment may lead to a higher disability risk, which is much higher than the simple sum of the two individual effects. Future interventions are required to target these symptoms simultaneously to reduce the risks of disability. Geriatr Gerontol Int 2022; 22: 1025-1031.

Organo-macrocycle-containing hierarchical metal-organic frameworks and cages: design, structures, and applications.

Developing hierarchical ordered systems is challenging. Using organo-macrocycles to construct metal-organic frameworks (MOFs) and porous coordination cages (PCCs) provides an efficient way to obtain hierarchical assemblies. Macrocycles, such as crown ethers, cyclodextrins, calixarenes, cucurbiturils, and pillararenes, can be incorporated within MOFs/PCCs and they also endow the resultant composites with enhanced properties and functionalities. This review summarizes recent developments of organo-macrocycle-containing hierarchical MOFs/PCCs, emphasizing applications and structure-property relationships of these hierarchically porous materials. This review provides insights for future research on hierarchical self-assembly using macrocycles as building blocks and functional ligands to extend the applications of the composites.

The Adhesion and Spoilage of Shewanella putrefaciens in Tilapia.

Shewanella putrefaciens is a typical spoilage bacteria organism in seafood. The adhesion ability of three S. putrefaciens strains (HR-15, JR-18, HC-71) isolated from putrefied tilapia were evaluated by mucus adhesion in vitro and intestinal adhesion in vivo. The results of the spoilage of the inoculated fish fillets and spoilage of the refrigerated fish both showed that the adhesion ability of S. putrefaciens was positively correlated with the spoilage ability. High-throughput sequencing and GC-MS results showed that S. putrefaciens with high adhesion ability also significantly changed the intestinal flora of fish, causing an increase in the intestinal bacteria such as Plesionomas, Macellibacteroides, Acinetobacter, and Legionella, which then led to the increase in volatile substances such as low-grade aldehydes, alcohols, and ketones in the fish, serious fatty acid oxidation, and excitement of the fishy smell.

The association between healthy aging index and trajectories of disability: a population-based cohort study.

BACKGROUND: Healthy aging index (HAI) could predict adverse health consequences including mortality and disability independent of age and comorbidity. We investigated the role of HAI on trajectories of disability throughout later life based on a nationally representative sample. METHODS: We examined 1733 participants aged over 60 years from the China Health and Retirement Longitudinal Study (CHARLS) followed for 7 years/4 waves repeatedly. Systolic blood pressure [SBP], cognitive function, cystatin C, peak expiratory flow [PEF], and fasting glucose were categorized using tertile or clinical reference range, and scored as 0 (healthiest), 1 (less healthy) and 2 (least healthy) respectively to further generate HAI summary scores (range 0-10). Disability was defined as the sum of impaired activities of daily living (ADL) and instrumental activities of daily living (IADL). We used linear mixed-effects model to study the association between HAI and trajectories of disability. RESULTS: A total of 10.5% of participants represented in the healthiest group and 22.5% ended up as the least healthy. After adjusting for all potential confounders, disability progression was significantly faster (ß = 0.27, 95% CI 0.11-0.42) in the least healthy group when comparing with the healthiest. CONCLUSION: Our findings suggest that HAI is associated with disability progression among adults aged over 60 years old. It might be beneficial for future interventions to specifically target older adults with high HAI scores as a means of reducing disability.

The efficacy and safety of Iodine-131-metaiodobenzylguanidine therapy in patients with neuroblastoma: a meta-analysis.

OBJECTIVE: Neuroblastoma is a common extracranial solid tumor of childhood. Recently, multiple treatments have been practiced including Iodine-131-metaiodobenzylguanidine radiation (131I-MIBG) therapy. However, the outcomes of efficacy and safety vary greatly among different studies. The aim of this meta-analysis is to evaluate the efficacy and safety of 131I-MIBG in the treatment of neuroblastoma and to provide evidence and hints for clinical decision-making. METHODS: Medline, EMBASE database and the Cochrane Library were searched for relevant studies. Eligible studies utilizing 131I-MIBG in the treatment of neuroblastoma were included. The pooled outcomes (response rates, adverse events rates, survival rates) were calculated using either a random-effects model or a fixed-effects model considering of the heterogeneity. RESULTS: A total of 26 clinical trials including 883 patients were analyzed. The pooled rates of objective response, stable disease, progressive disease, and minor response of 131I-MIBG monotherapy were 39%, 31%, 22% and 15%, respectively. The pooled objective response rate of 131I-MIBG in combination with other therapies was 28%. The pooled 1-year survival and 5-year survival rates were 64% and 32%. The pooled occurrence rates of thrombocytopenia and neutropenia in MIBG monotherapy studies were 53% and 58%. In the studies of 131I-MIBG combined with other therapies, the pooled occurrence rates of thrombocytopenia and neutropenia were 79% and 78%. CONCLUSION: 131I-MIBG treatment alone or in combination of other therapies is effective on clinical outcomes in the treatment of neuroblastoma, individualized 131I-MIBG is recommended on a clinical basis.

High-κ Polyimide-Based Dielectrics by Introducing a Functionalized Metal-Organic Framework.

In this work, novel metal-organic framework/polyimide (MOF/PI) composite films possessing dielectric properties were synthesized via a solution blending method. UiO-66 and UiO-66-NH2 nanoparticles were first prepared by a hydrothermal method and added into PI to obtain the composite films. Compared with pure PI, the dielectric properties of the MOF/PI composites were substantially enhanced. The amine functionalization gave UiO-66-NH2/PI composite films better dielectric properties in comparison with UiO-66/PI composite films because of improved interaction between PI and UiO-66-NH2. It showed that the dielectric constant of the PI composite film containing 20 wt% UiO-66-NH2 is 8.8 at 102 Hz, which was approximately 2.5 times that of the pure PI (3.5 at 102 Hz). The dielectric loss of the composite film was less than 0.034. Moreover, the breakdown strength of 20 wt% UiO-66-NH2/PI composite films was found to be 208 kV/mm. We describe this new perspective for the preparation of high-performance polymer-based dielectric materials and their application as electrical materials.

Air pollution increased risk of reproductive system diseases: a 5-year outcome analysis of different pollutants in different seasons, ages, and genders.

Air pollution remains a serious environmental problem worldwide, and the effects of air pollutants with reproductive system diseases have already attracted extensive attention. The present study investigated the risk of air pollutants on reproductive system diseases, based on daily medical visits (DMV) of the past 5 years in central China. Data of DMV outpatients with reproductive system diseases were obtained from a general hospital in Zhengzhou, October 28, 2013 to May 31, 2018, as well as atmospheric pollutants data. Correlation of air pollutants and DMV was analyzed with distributed lag nonlinear model (DLNM), including total cases of reproductive system diseases, and in different seasons (spring, summer, autumn, and winter), genders (male and female), and age groups (<26, 26-35, and >35 years old). A total of 374,558 visits were included. NO2 was most closely relevant to incidence risk of total cases analysis with each increased interquartile ranges (IQRs) in the 6 pollutants, with 30-day lag. Relationship to pollutants was more sensitive in fall, >35 years old, and male groups than in other seasons, ages, and females, and NO2 had the highest risk on reproductive diseases. Air pollution increased risk of reproductive system diseases, and different pollutants played different roles in different seasons, ages, and genders. The results of this study will provide evidence for effective air quality controlling and human reproductive protection.

Effective-component compatibility of Bufei Yishen formula protects COPD rats against PM2.5-induced oxidative stress via miR-155/FOXO3a pathway.

Ambient particulate matter <2.5 µm (PM2.5) has been identified as a critical risk factor in chronic obstructive pulmonary disease (COPD) exacerbation, but therapies for this condition are limited. Effective-component compatibility of Bufei Yishen formula (ECC-BYF) exhibits beneficial efficacy on COPD rats. However, its effect on PM2.5-aggravated COPD rats are considered to be uncertain. In this study, we used an established PM2.5-aggravated COPD rat model in vivo to evaluate the protective effect of ECC-BYF, and focused on its antioxidative role in PM2.5-stimulated bronchial epithelial cells via regulating microRNA (miR)-155/ forkhead box class O3a (FOXO3a) pathway. As expected, PM2.5-aggravated COPD rats showed a reduction of lung function, persistent lung inflammation, and remodeling of lung tissue. In comparison, ECC-BYF administration significantly enhanced lung function, alleviated alveolar destruction, inflammatory cell infiltration, mucus hypersecretion, and collagen deposition, along with diminishing inflammatory cytokine production and oxidative stress. Furthermore, ECC-BYF pretreatment markedly decreased the fluorescence intensity of reactive oxygen species (ROS) in PM2.5-induced human bronchial epithelial (Beas-2B) cells and primary mouse tracheal epithelial cells (MTECs), as well as reversing the imbalance between oxidants and antioxidants in Beas-2B. Meanwhile, ECC-BYF elevated FOXO3a while inhibiting miR-155 expression dose -dependently. In vitro transfection of miR-155 mimic into Beas-2B significantly decreased FOXO3a protein expression, accompanied by the reduced superoxide dismutase 2 (SOD2) and catalase (CAT) expressions, thus eliminating the protective effect of ECC-BYF on PM2.5-evoked oxidative stress. Nonethless, FOXO3a overexpression could partially restore the antioxidative effect of ECC-BYF. In conclusion, ECC-BYF can protect pre-existing COPD against PM2.5 contamination by exerting a profound antioxidative influence via regulating miR-155/FOXO3a signaling.