Assessing the relative effectiveness of various ultrasound-guided ablation techniques for treating benign thyroid nodules: A systematic review and network meta-analysis.

BACKGROUND: Benign thyroid nodules (BTNs) represent a prevalent clinical challenge globally, with various ultrasound-guided ablation techniques developed for their management. Despite the availability of these methods, a comprehensive evaluation to identify the most effective technique remains absent. This study endeavors to bridge this knowledge gap through a network meta-analysis (NMA), aiming to enhance the understanding of the comparative effectiveness of different ultrasound-guided ablation methods in treating BTNs. METHODS: We comprehensively searched PubMed, Embase, Cochrane, Web of Science, Ovid, SCOPUS, and ProQuest for studies involving 16 ablation methods, control groups, and head-to-head trials. NMA was utilized to evaluate methods based on the percentage change in nodule volume, symptom score, and cosmetic score. This study is registered in INPLASY (registration number 202260061). RESULTS: Among 35 eligible studies involving 5655 patients, NMA indicated that RFA2 (radiofrequency ablation, 2 sessions) exhibited the best outcomes at 6 months for percentage change in BTN volume (SUCRA value 74.6), closely followed by RFA (SUCRA value 73.7). At 12 months, RFA was identified as the most effective (SUCRA value 81.3). Subgroup analysis showed RFA2 as the most effective for solid nodule volume reduction at 6 months (SUCRA value 75.6), and polidocanol ablation for cystic nodules (SUCRA value 66.5). CONCLUSION: Various ablation methods are effective in treating BTNs, with RFA showing notable advantages. RFA with 2 sessions is particularly optimal for solid BTNs, while polidocanol ablation stands out for cystic nodules.

Two-sample Mendelian randomization analysis reveals causal relationships between blood lipids and venous thromboembolism.

Venous Thromboembolism (VTE) is a complex disease that can be classified into two subtypes: Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE). Previous observational studies have shown associations between lipids and VTE, but causality remains unclear. Hence, by utilizing 241 lipid-related traits as exposures and data from the FinnGen consortium on VTE, DVT, and PE as outcomes, we conducted two-sample Mendelian randomization (MR) analysis to investigate causal relationships between lipids and VTE, DVT and PE. The MR results identified that fatty acid (FA) unsaturation traits (Ratio of bis-allylic bonds to double bonds in lipids, and Ratio of bis-allylic bonds to total fatty acids in lipids) were associated with VTE (OR [95% CI]: 1.21 [1.15-1.27]; 1.21 [1.13-1.30]), DVT (OR [95%CI]: 1.24 [1.16-1.33]; 1.26 [1.16-1.36]) and PE (OR [95%CI]: 1.18 [1.08-1.29]; 1.18 [1.09-1.27]). Phosphatidylcholines exhibit potential causal effects on VTE and PE. Phosphatidylcholine acyl-alkyl C40:4 (PC ae C40:4) was negatively associated with VTE (OR [95% CI]: 0.79 [0.73-0.86]), while phosphatidylcholine diacyl C42:6 (PC aa C42:6) and phosphatidylcholine acyl-alkyl C36:4 (PC ae C36:4) were positively associated with PE (OR [95%CI]: 1.44 [1.20-1.72]; 1.22 [1.10-1.35]). Additionally, we found that medium LDL had a protective effect on VTE. Our study indicates that higher FA unsaturation may increase the risk of VTE, DVT, and PE. Different types of phosphatidylcholine have either promotive or inhibitory effects on VTE and PE, contributing to a better understanding of the risk factors for VTE.

Threshold of hyperglycaemia associated with mortality in critically ill patients: a multicentre, prospective, observational study using continuous glucose monitoring.

AIMS/HYPOTHESIS: Continuous glucose monitoring (CGM) provides comprehensive information on the exposure to dysglycaemia. This study aimed to investigate the threshold of hyperglycaemia related to mortality risk in critically ill patients using CGM technology. METHODS: A total of 293 adult critically ill patients admitted to intensive care units of five medical centres were prospectively included between May 2020 and November 2021. Participants wore intermittently scanned CGM for a median of 12.0 days. The relationships between different predefined time above ranges (TARs), with the thresholds of hyperglycaemia ranging from 7.8 to 13.9 mmol/l (140-250 mg/dl), and in-hospital mortality risk were assessed by multivariate Cox proportional regression analysis. Time in ranges (TIRs) of 3.9 mmol/l (70 mg/dl) to the predefined hyperglycaemic thresholds were also assessed. RESULTS: Overall, 66 (22.5%) in-hospital deaths were identified. Only TARs with a threshold of 10.5 mmol/l (190 mg/dl) or above were significantly associated with the risk of in-hospital mortality, after adjustment for covariates. Furthermore, as the thresholds for TAR increased from 10.5 mmol/l to 13.9 mmol/l (190 mg/dl to 250 mg/dl), the hazards of in-hospital mortality increased incrementally with every 10% increase in TARs. Similar results were observed concerning the associations between TIRs with various upper thresholds and in-hospital mortality risk. For per absolute 10% decrease in TIR 3.9-10.5 mmol/l (70-190 mg/dl), the risk of in-hospital mortality was increased by 12.1% (HR 1.121 [95% CI 1.003, 1.253]). CONCLUSIONS/INTERPRETATION: A glucose level exceeding 10.5 mmol/l (190 mg/dl) was significantly associated with higher risk of in-hospital mortality in critically ill patients.

Engineering Nanomedicine for Non-Viral RNA-Based Gene Therapy of Glioblastoma.

Glioblastoma multiforme (GBM) is the most common type of malignant tumor of the central nervous system, characterized by aggressiveness, genetic instability, heterogenesis, and unpredictable clinical behavior. Disappointing results from the current clinical therapeutic methods have fueled a search for new therapeutic targets and treatment modalities. GBM is characterized by various genetic alterations, and RNA-based gene therapy has raised particular attention in GBM therapy. Here, we review the recent advances in engineered non-viral nanocarriers for RNA drug delivery to treat GBM. Therapeutic strategies concerning the brain-targeted delivery of various RNA drugs involving siRNA, microRNA, mRNA, ASO, and short-length RNA and the therapeutical mechanisms of these drugs to tackle the challenges of chemo-/radiotherapy resistance, recurrence, and incurable stem cell-like tumor cells of GBM are herein outlined. We also highlight the progress, prospects, and remaining challenges of non-viral nanocarriers-mediated RNA-based gene therapy.

Iodine Nutrition, Thyroid-stimulating Hormone, and Related Factors of Postpartum Women from three Different Areas in China: A Cross-sectional Survey.

Objective: Studies on the relationship between iodine, vitamin A (VA), and vitamin D (VD) and thyroid function are limited. This study aimed to analyze iodine and thyroid-stimulating hormone (TSH) status and their possible relationships with VA, VD, and other factors in postpartum women. Methods: A total of 1,311 mothers (896 lactating and 415 non-lactating) from Hebei, Zhejiang, and Guangxi provinces were included in this study. The urinary iodine concentration (UIC), TSH, VA, and VD were measured. Results: The median UIC of total and lactating participants were 142.00 µg/L and 139.95 µg/L, respectively. The median TSH, VA, and VD levels in all the participants were 1.89 mIU/L, 0.44 µg/mL, and 24.04 ng/mL, respectively. No differences in the UIC were found between lactating and non-lactating mothers. UIC and TSH levels were significantly different among the three provinces. The rural UIC was higher than the urban UIC. Obese mothers had a higher UIC and a higher prevalence of excessive TSH. Higher UICs and TSHs levels were observed in both the VD deficiency and insufficiency groups than in the VD-sufficient group. After adjustment, no linear correlation was observed between UIC and VA/VD. No interaction was found between vitamins A/D and UIC on TSH levels. Conclusion: The mothers in the present study had no iodine deficiency. Region, area type, BMI, and VD may be related to the iodine status or TSH levels.

In-situ texturing hollow carbon host anchored with Fe single atoms accelerating solid-phase redox for Li-Se batteries.

Se-based cathodes have caught tremendous attention owing to their comparable volumetric capacity and better electronic conductivity to S cathodes. However, its low utilization ratio and sluggish redox kinetics due to the high reaction barrier of solid-phase transformation from Se to Li2Se limit its practical application. Herein, an in-situ texturing hollow carbon host by gas-solid interface reaction anchored with Fe single-atomic catalyst is designed and prepared for advanced Li-Se batteries. This Se host presents high pore volume of 1.49 cm3 g-1, Fe single atom content of 1.53 wt%, and its specific structure protects single-atomic catalyst from the destructive reaction environment, thus balancing catalytic activity and durability. After Se loading by reduction of H2SeO3, this homogenous Se-based cathode delivers a superior rate capacity of 431.3 mA h g-1 at 4C, and great discharge capacity of 301.8 mA h g-1 after 1000 cycles at 10C, with high Li-ion diffusion coefficient and capacitance-contributed ratio. The distribution of relaxation times analysis verifies solid-phase transformation mechanism of this cathode and density functional theory calculations confirm the adsorption and bidirectionally catalysis effect of Fe single-atomic catalyst. This work provides a new strategy to prepare high-efficient Se cathode associated with non-noble metal single atoms for high-performance Li-Se batteries.

Characteristics of the time processing of adults' strongest sustained attentional bias toward neutral infant faces.

Previous studies have shown that adults exhibit the strongest attentional bias toward neutral infant faces when viewing faces with different expressions at different attentional processing stages due to different stimulus presentation times. However, it is not clear how the characteristics of the temporal processing associated with the strongest effect change over time. Thus, we combined a free-viewing task with eye-tracking technology to measure adults' attentional bias toward infant and adult faces with happy, neutral, and sad expressions of the same face. The results of the analysis of the total time course indicated that the strongest effect occurred during the strategic processing stage. However, the results of the analysis of the split time course revealed that sad infant faces first elicited adults' attentional bias at 0 to 500 ms, whereas the strongest effect of attentional bias toward neutral infant faces was observed at 1000 to 3000 ms, peaking at 1500 to 2000 ms. In addition, women and men had no differences in their responses to different expressions. In summary, this study provides further evidence that adults' attentional bias toward infant faces across stages of attention processing is modulated by expressions. Specifically, during automatic processing adults' attentional bias was directed toward sad infant faces, followed by a shift to the processing of neutral infant faces during strategic processing, which ultimately resulted in the strongest effect. These findings highlight that this strongest effect is dynamic and associated with a specific time window in the strategic process.

Botulinum toxin type A inhibits M1 macrophage polarization by deactivation of JAK2/STAT1 and IκB/NFκB pathway and contributes to scar alleviation in aseptic skin wound healing.

The non-neuronal and non-muscular effects of botulinum toxin type A (BTXA) on scar reduction has been discovered. This study was designed to investigate the effects of BTXA on macrophages polarization during the early stage of skin repair. A skin defect model was established on the dorsal skin of SD rats. BTXA was intracutaneous injected into the edge of wound immediately as the model was established. Histological examinations were performed on scar samples. Raw 264.7 was selected as the cell model of recruited circulating macrophages, and was induced for M1 polarization by LPS. Identify the signaling pathways that primarily regulated M1 polarization and respond to BTXA treatment. Application of BTXA at early stage of injury significantly reduced the scar diameter without delaying wound closure. BTXA treatment improved fiber proliferation and arrangement, and inhibited angiogenesis in scar granular tissue. The number of M1 macrophages and the levels of pro-inflammation were decreased after treated with BTXA in scar tissues. LPS activated JAK2/STAT1 and IκB/NFκB pathways were downregulated by BTXA, as well as LPS induced M1 polarization. At early stage of skin wound healing, injection of BTXA effectively reduced the number of M1 macrophages and the levels of pro-inflammatory mediators which contributes to scar alleviation. BTXA resisted the M1 polarization of macrophages induced by LPS via deactivating the JAK2/STAT1 and IκB/NFκB pathways.

Structural alterations of brain in different disease states of Crohn's disease: Results of a cross-sectional study in a Chinese hospital.

Rationale and objectives: To investigate alterations in the brain structure in patients with Crohn's disease in activity (CD-A) and in remission (CD-R) compared to healthy controls (HCs) and explore the relationship between gray matter volume (GMV) and psychological disorders. Materials and methods: A total of 127 CD patients (62 CD-A, 65 CD-R) and 92 healthy controls (HCs) were enrolled and analyzed in this study. The Crohn's disease activity index (CDAI) was used as the grouping criteria. Voxel-based morphometry (VBM) was applied to investigate gray matter volume (GMV), white matter volume (WMV) and global cerebrospinal fluid (CSF) volume alterations. Pearson correlation analysis was used to evaluate the relationships. Results: The CSF volume was negatively correlated with the disease duration in CD-R. Increased GMV of CD was observed in the parahippocampal gyrus, precentral gyrus, precuneous cortex, and subcallosal cortex, decreased was located in the occipital pole, precentral gyrus, inferior temporal gyrus, middle frontal gyrus, angular gyrus, frontal pole, lateral occipital cortex, and lingual gyrus. The GMV in the right temporal pole, left precuneous cortex, and left cingulate gyrus had a positive correlation with erythrocyte and hemoglobin in CD groups. The GMV in the right frontal pole, right postcentral gyrus, and left cingulate gyrus had a negative correlation with somatization in the CD groups. The GMV in the right temporal pole had a negative correlation with psychoticism and other in the CD groups. The GMV in the left cingulate gyrus was positive with bowel symptoms and systemic symptoms in the CD groups. Conclusion: Alterations of GMV in CD-A and CD-R and associated correlation with psychological disorders may provide evidence for possible neuro-mechanisms of CD with psychological disorders.

A potential brain functional biomarker distinguishing patients with Crohn's disease with different disease stages: a resting-state fMRI study.

Background: The previous studies have demonstrated that patients with Crohn's disease in remission (CD-R) have abnormal alterations in brain function. However, whether brain function changes in patients with Crohn's disease in activity (CD-A) and the relationship with CD-R are still unclear. In this study, we aimed to investigate whether the different levels of disease activity may differentially affect the brain function and to find the brain functional biomarker distinguishing patients with different disease stages by measuring the amplitude of low frequency fluctuations (ALFF). Methods: 121 patients with CD and 91 healthy controls (HCs) were recruited. The clinical and psychological assessment of participants were collected. The criteria for the disease activity were the Crohn's disease activity index (CDAI) scores. CD-R refers to CD patients in remission which the CDAI score is less than 150. Conversely, CD-A refers to CD patients in activity which the CDAI score is ≥150. The ALFF was compared among three groups by performing one-way analysis of variance, followed by a post hoc two-sample t-test. Differences among the groups were selected as seeds for functional connectivity analyses. We also investigated the correlation among clinical, psychological scores and ALFF. Binary logistic regression analysis was used to examine the unique contribution of the ALFF characteristics of the disease stages. Results: There were widespread differences of ALFF values among the 3 groups, which included left frontal pole (FP_L), right supramarginal gyrus (SG_R), left angular gyrus (AG_L), right cingulate gyrus (CG_R), right intracalcarine cortex (IC_R), right parahippocampal gyrus (PG_R), right lingual gyrus (LG_R), right precuneous cortex (PC_R), left occipital fusiform gyrus (OFG_L). Significant brain regions showing the functional connections (FC) increased in FP_L, SG_R, PC_R and OFG_L between CD-A and HCs. The erythrocyte sedimentation rate had a negative correlation with the ALFF values in PC_R in the patients with CD. The phobic anxiety values had a negative correlation with the ALFF values in OFG_L. The psychoticism values had a negative correlation with ALFF values in the IC_R. And the hostility values had a positive correlation with the ALFF values in CG_R. Significant brain regions showing the FC increased in FP_L, SG_R, CG_R, PG_R, LG_R and OFG_L between CD-R and HCs. In binary logistic regression models, the LG_R (beta = 5.138, p = 0.031), PC_R (beta = 1.876, p = 0.002) and OFG_L (beta = 3.937, p = 0.044) was disease stages predictors. Conclusion: The results indicated the significance of the altered brain activity in the different disease stages of CD. Therefore, these findings present a potential identify neuroimaging-based brain functional biomarker in CD. Additionally, the study provides a better understanding of the pathophysiology of CD.

Cyclic Peptide Keap1-Nrf2 Protein-Protein Interaction Inhibitors: Design, Synthesis, and In Vivo Treatment of Acute Lung Injury.

Directly blocking the Keap1-Nrf2 pathway is a promising strategy for the mitigation of acute lung injury (ALI). Peptide Keap1-Nrf2 inhibitors have been reported to have a high Keap1 binding affinity. However, these inhibitors showed weak activity in cells and/or animals. In this study, we designed a series of linear peptides from an Nrf2-based 9-mer Ac-LDEETGEFL-NH2. To improve the cellular activity, we further designed cyclic peptides based on the crystal complex of Keap1 with a linear peptide. Among them, cyclic 9-mer ZC9 targeting Keap1 showed a better affinity (KD2 = 51 nM). Specifically, it exhibited an acceptable water solubility (>38 mg/mL), better cell permeability, cell activity, and metabolic stability (serum t1/2 > 24 h). In the in vitro LPS-induced oxidative damages and ALI model, ZC9 showed significant dose-response reversal activity without apparent toxicity. In conclusion, our results suggested ZC9 as a lead cyclic peptide targeting the Keap1-Nrf2 pathway for ALI clinical treatment.

Cell Membrane Camouflaged Biomimetic Nanoparticles as a Versatile Platform for Brain Diseases Treatment.

Although there are various advancements in biomedical in the past few decades, there are still challenges in the treatment of brain diseases. The main difficulties are the inability to deliver a therapeutic dose of the drug to the brain through the blood-brain barrier (BBB) and the serious side effects of the drug. Thus, it is essential to select biocompatible drug carriers and novel therapeutic tools to better enhance the effect of brain disease treatment. In recent years, biomimetic nanoparticles (BNPs) based on natural cell membranes, which have excellent biocompatibility and low immunogenicity, are widely used in the treatment of brain diseases to enable the drug to successfully cross the BBB and target brain lesions. BNPs can prolong the circulation time in vivo, are more conducive to drug aggregation in brain lesions. Cell membranes (CMs) from cancer cells (CCs), red blood cells (RBCs), white blood cells (WBCs), and so on are used as biomimetic coatings for nanoparticles (NPs) to achieve the ability to target, evade clearance, or stimulate the immune system. This review summarizes the application of different cell sources as BNPs coatings in the treatment of brain diseases and discusses the possibilities and challenges of clinical translation.

Laser-Induced Preparation of Anderson-Type Polyoxometalate-Derived Sulfide/Oxide Electrocatalysts for Electrochemical Water Oxidation.

Developing cost-effective and high-active electrocatalysts is vital to enhance the electrocatalytic performance for oxygen evolution reaction (OER). However, traditional pyrolysis methods require complicated procedures, exact temperatures, and long reaction times, leading to high costs and low yields of electrocatalysts in potential industrial applications. Herein, a rapid and economic laser-induced preparation strategy is proposed to synthesize three bimetallic sulfide/oxide composites (MMoOS, M=Fe, Co, and Ni) on a nickel foam (NF) substrate. A focused CO2 laser with high energy is applied to decompose Anderson-type polyoxometalate (POM)-based precursors, enabling the creation of abundant heteropore and defective structures in the MMoOS composites that have multi-components of MS/Mo4O11/MoS2. Remarkably, owing to the structural interactions between the active species, FeMoOS shows superior electrocatalytic performance for OER in an alkaline medium, exhibiting a low overpotential of 240 mV at 50 mA cm-2, a small Tafel slope of 79 mV dec-1, and good durability for 80 h. Physical characterizations after OER imply that partially dissolved Mo-based species and new-formed NiO/NiOOH can effectively uncover abundant active sites, fasten charge transfer, and modify defective structures. This work provides a rapid laser-induced irradiation method for the synthesis of POM-derived nanocomposites as promoted electrocatalysts.

Total synthesis and structural modification of the dibenzylbutane lignan LCA as a potent anti-inflammatory agent against LPS-induced acute lung injury.

Acute lung injury (ALI) is a serious public health problem associated with high morbidity and mortality. However, few efficacious drugs are clinically available. Inhibition of proinflammatory cytokines is considered to be a promising method for the treatment of inflammatory diseases. Herein, the total synthesis of a dibenzylbutane lignan, 9'-O-di-(E)-feruloyl-meso-5,5'-dimethoxysecoisolariciresinol (LCA), was completed. A series of LCA derivatives were designed and synthesized, and their anti-inflammatory activities were evaluated. Derivative 14r significantly inhibited LPS-induced expression of NO and the proinflammatory cytokines TNF-α, IL-6, and IL-1ß in RAW 264.7 cells and inhibited activation of the NF-κB pathway. Compound 14r reduced LPS-induced pulmonary inflammation and ALI in mice. It showed significant protective effects against LPS-induced ALI in mice and significantly reduced levels of proinflammatory cytokines in serum and bronchoalveolar lavage fluid. The ratio of wet weight to dry weight of lung tissue was normalized by compound 14r, which was consistent with suppression of neutrophil infiltration and production of proinflammatory cytokines. Compound 14r reduced the mRNA expression of some proinflammatory cytokines, improved histopathologic changes, and reduced macrophage infiltration in lung tissues. Collectively, these results suggest a new series of LCA derivatives that could be promising anti-inflammatory agents for ALI treatment.

Further structural optimization and SAR study of sungsanpin derivatives as cell-invasion inhibitors.

Metastasis is one of the major causes of death in patients with cancer, and cell invasion plays a fundamental part in this process. Because of the absence of efficacious treatments, caring for these patients is challenging. Recently, we optimized the structure of the naturally occurring lasso peptide sungsanpin. We identified two peptides, octapeptide S3 and cyclic peptide S4, which inhibited invasion into A549 cells effectively. We undertook an alanine scan of S3 to explore the structure-activity relationship. The linear octapeptide S3-4 and cyclic peptide S4-1 exhibited improved inhibition of invasion into A549 cells. We modified S3-4 to obtain S3-4K, which displayed much higher inhibitory activity against invasion into A549 cells than S3-4. Of all peptides tested, S4-1 upregulated significantly mRNA of tissue inhibitor matrix metalloproteinase TIMP-1 and TIMP-2.

Factors Influencing Plasma Concentrations of Valproic Acid in Pediatric Patients with Epilepsy and the Clinical Significance of CYP2C9 Genotypes in Personalized Valproic Acid Therapy.

BACKGROUND: The aim of this study was to investigate the factors affecting plasma valproic acid (VPA) concentration in pediatric patients with epilepsy and the clinical significance of CYP2C9 gene polymorphisms in personalized dosing using therapeutic drug monitoring and pharmacogenetic testing. METHODS: The medical records of children with epilepsy who underwent therapeutic drug monitoring at our institution between July 2022 and July 2023 and met the inclusion criteria were reviewed. Statistical analysis was performed to determine whether age, sex, blood ammonia, liver function, kidney function, and other characteristics affected the concentration-to-dose ratio of VPA (CDRV) in these patients. To investigate the effect of CYP2C9 polymorphisms on CDRV, DNA samples were collected from patients and the CYP2C9 genotypes were identified using real-time quantitative PCR. RESULTS: The mean age of 208 pediatric patients with epilepsy was 5.50 ± 3.50 years. Among these patients, 182 had the CYP2C9 *1/*1 genotype, with a mean CDRV (mcg.kg/mL.mg) of 2.64 ± 1.46, 24 had the CYP2C9 *1/*3 genotype, with a mean CDRV of 3.28 ± 1.74, and 2 had the CYP2C9 *3/*3 genotype, with a mean CDRV of 6.46 ± 3.33. There were statistical differences among these 3 genotypes (P < 0.05). The CDRV in these patients were significantly influenced by age, aspartate aminotransferase, total bilirubin, direct bilirubin, globulin, albumin/globulin ratio, prealbumin, creatinine, and CYP2C9 polymorphisms. In addition, multivariate linear regression analysis identified total bilirubin, direct bilirubin, and CYP2C9 polymorphisms as independent risk factors for high CDRV. CONCLUSIONS: Liver problems and mutations in the CYP2C9 gene increase VPA levels. This underscores the importance of considering these factors when prescribing VPA to children with epilepsy, thereby enhancing the safety and efficacy of the therapy.

Controlled Assembly of a Dawson-like Antimoniotungstate-Supported Trefoil-type Trimer with Good Proton Conductivity Performance.

With the excellent properties of POM in the field of proton conductivity, the preparation of POM-based proton-conductive materials has burst into life. Herein, an unprecedented Sb-templated all-inorganic trimer Na8H18.64[(SbW14O52)3(Sb2W6.12Ru5.88O18)]·85H2O (1), which is based on tetravacant Dawson-like [SbW14O52]17- blocks and exhibits a trefoil type with D3 symmetry, has been successfully designed and synthesized by the assembly of simple materials with a one-pot hydrothermal method under acidic conditions. Also, compound 1 is systematically characterized by single-crystal X-ray diffraction, PXRD, ESI-MS, IR spectroscopy, UV-vis, elemental analysis, and TGA. Crystal structure data analysis demonstrates that compound 1 is constructed by a hexagonal prismatic heterometallic {Sb2W6.12Ru5.88O18} core and three equivalent {SbW14} units bridged through µ2-O atoms in periphery. Subsequently, further property experiments show that compound 1 exhibits high proton conductivity with a conductivity value (σ) of 3.07 × 10-2 S cm-1 at 75 °C and 80% relative humidity (RH). The activation energy of compound 1 evaluated by the Arrhenius plots is 0.22 eV, which indicates that the Grotthuss mechanism is dominant during the process of proton transfer.

Design, synthesis, evaluation and optimization of novel azole analogues as potent antifungal agents.

In order to develop antifungal drugs, a series of novel azole analogues were designed and synthesized based on our previous work. Most of the target compounds had broad-spectrum antifungal activity, which showed excellent to moderate inhibitory activity against the tested strains, except A. fum 0504656. Among these, compounds B3, B7, B8, B11, B12 and E9 showed excellent activity against C. alb Y0109 and C. alb SC5314 (with the MIC80: 0.0156 ug/mL). In addition, compound B3 showed the best inhibitory activity against fluconazole-resistant strains C. alb 901 and C. alb 904, and had low toxicity against NIH/3T3 cells at the effective MIC range against fungi. Structure-activity relationship and docking studies of the derivatives suggest that the presence of the 2-fluoro-4-hydroxyphenyl and 1,2,3-triazole group enhance the antifungal activity of the compounds, which may be related to the interaction of the key groups with the amino acids surrounding the target enzyme.

Relationship between family function, self-perceived burden and loneliness in patients with type 2 diabetes mellitus: a cross-lagged analysis.

AIMS: To explore the inter-predictive role and causal relationship between family functioning, self-perceived burden and loneliness in people with type 2 diabetes. METHODS: In this study, patients with type 2 diabetes admitted to two tertiary care hospitals in China were selected for an 8-month follow-up, and the patients' scores on the Family Functioning, Self-perceived Burden, and Loneliness scales were measured repeatedly at three time periods: during hospitalisation (T1), 1 month after discharge (T2), and 3 months after discharge (T3). RESULTS: The results showed that family function at the T1 time point had a negative predictive effect on self-perceived burden at the T2 time point, ß = - 0.43, P = 0.005. Loneliness at the T1 time point had a positive predictive effect on self-perceived burden at the T2 time point, ß = 0.08, P = 0.021. Unlike the pathway at time point T1, family functioning at time point T2 negatively predicted loneliness at time point T3, ß = - 0.32, P = 0.013. Loneliness at time point T2 positively predicted family functioning at time point T3, ß = 0.025, P = 0.013. Loneliness at time point T2 negatively predicted self-perceived burden at time point T3 (P = 0.011). CONCLUSIONS: The results of the cross-lagged analysis show that there is a mutually predictive and moderating relationship between family functioning and loneliness in patients with type 2 diabetes. Loneliness can predict the level of self-perceived burden at the next time point.