An Exploratory, Randomized, Double-Blind Clinical Trial of Dipraglurant for Blepharospasm.

BACKGROUND: Blepharospasm is treated with botulinum toxin, but obtaining satisfactory results is sometimes challenging. OBJECTIVE: The aim is to conduct an exploratory trial of oral dipraglurant for blepharospasm. METHODS: This study was an exploratory, phase 2a, randomized, double-blind, placebo-controlled trial of 15 participants who were assigned to receive a placebo or dipraglurant (50 or 100 mg) and assessed over 2 days, 1 and 2 hours following dosing. Outcome measures included multiple scales rated by clinicians or participants, digital video, and a wearable sensor. RESULTS: Dipraglurant was well tolerated, with no obvious impact on any of the measurement outcomes. Power analyses suggested fewer subjects would be required for studies using a within-subject versus independent group design, especially for certain measures. Some outcome measures appeared more suitable than others. CONCLUSION: Although dipraglurant appeared well tolerated, it did not produce a trend for clinical benefit. The results provide valuable information for planning further trials in blepharospasm. © 2024 International Parkinson and Movement Disorder Society.

Early predictors of severe left main and/or three-vessel disease in patients with non-ST-segment elevation myocardial infarction: A dual-center retrospective study.

BACKGROUND: Early detection of patients concomitant with left main and/or three-vessel disease (LM/3VD) and high SYNTAX score (SS) is crucial for determining the most effective revascularization options regarding the use of antiplatelet medications and prognosis risk stratification. However, there is a lack of study for predictors of LM/3VD with SS in patients with non-ST-segment elevation myocardial infarction (NSTEMI). We aimed to identify potential factors that could predict LM/3VD with high SS (SS > 22) in patients with NSTEMI. METHODS: This dual-center retrospective study included a total of 481 patients diagnosed with NSTEMI who performed coronary angiography procedures. Clinical factors on admission were collected. The patients were divided into non-LM/3VD, Nonsevere LM/3VD (SS ≤ 22), and Severe LM/3VD (SS > 22) groups. To identify independent predictors, Univariate and logistic regression analyses were conducted on the clinical parameters. RESULTS: A total of 481 patients were included, with an average age of 60.9 years and 75.9% being male. Among these patients, 108 individuals had severe LM/3VD. Based on the findings of a multivariate logistic regression analysis, the extent of ST-segment elevation observed in lead aVR (OR: 7.431, 95% CI: 3.862-14.301, p < .001) and age (OR: 1.050, 95% CI: 1.029-1.071, p < .001) were identified as independent predictors of severe LM/3VD. CONCLUSION: This study indicated that the age of patients and the extent of ST-segment elevation observed in lead aVR on initial electrocardiogram were the independent predictive factors of LM/3VD with high SS in patients with NSTEMI.

Anomaly Detection of Permanent Magnet Synchronous Motor Based on Improved DWT-CNN Multi-Current Fusion.

The Permanent Magnet Synchronous Motor (PMSM) is the power source maintaining the stable and efficient operation of various pieces of equipment; hence, its reliability is crucial to the safety of public equipment. Convolutional Neural Network (CNN) models face challenges in extracting features from PMSM current data. A new Discrete Wavelet Transform Convolutional Neural Networks (DW-CNN) feature with fusion weight updating Long Short-Term Memory (LSTM) anomaly detection is proposed in this paper. This approach combines Discrete Wavelet Transform (DWT) with high and low-frequency separation processing and LSTM. The anomaly detection method adopts DWT and CNN by separating high and low-frequency processing. Moreover, this method combines the hybrid attention mechanism to extract the multi-current signal features and detects anomalies based on weight updating the LSTM network. Experiments on the motor bearing real fault dataset and the PMSM stator fault dataset prove the method's strong capability in fusing current features and detecting anomalies.

Towards a mechanistic understanding of variation in aquatic food chain length.

Ecologists have long sought to understand variation in food chain length (FCL) among natural ecosystems. Various drivers of FCL, including ecosystem size, resource productivity and disturbance, have been hypothesised. However, when results are aggregated across existing empirical studies from aquatic ecosystems, we observe mixed FCL responses to these drivers. To understand this variability, we develop a unified competition-colonisation framework for complex food webs incorporating all of these drivers. With competition-colonisation tradeoffs among basal species, our model predicts that increasing ecosystem size generally results in a monotonic increase in FCL, while FCL displays non-linear, oscillatory responses to resource productivity or disturbance in large ecosystems featuring little disturbance or high productivity. Interestingly, such complex responses mirror patterns in empirical data. Therefore, this study offers a novel mechanistic explanation for observed variations in aquatic FCL driven by multiple environmental factors.

Discovery of a first-in-class orally available HBV cccDNA inhibitor.

BACKGROUND & AIMS: The persistence of covalently closed circular DNA (cccDNA) in infected hepatocytes is the major barrier preventing viral eradication with existing therapies in patients with chronic hepatitis B. Therapeutic agents that can eliminate cccDNA are urgently needed to achieve viral eradication and thus HBV cure. METHODS: A phenotypic assay with HBV-infected primary human hepatocytes (PHHs) was employed to screen for novel cccDNA inhibitors. A HBVcircle mouse model and a uPA-SCID (urokinase-type plasminogen activator-severe combined immunodeficiency) humanized liver mouse model were used to evaluate the anti-HBV efficacy of the discovered cccDNA inhibitors. RESULTS: Potent and dose-dependent reductions in extracellular HBV DNA, HBsAg, and HBeAg levels were achieved upon the initiation of ccc_R08 treatment two days after the HBV infection of PHHs. More importantly, the level of cccDNA was specifically reduced by ccc_R08, while it did not obviously affect mitochondrial DNA. Additionally, ccc_R08 showed no significant cytotoxicity in PHHs or in multiple proliferating cell lines. The twice daily oral administration of ccc_R08 to HBVcircle model mice, which contained surrogate cccDNA molecules, significantly decreased the serum levels of HBV DNA and antigens, and these effects were sustained during the off-treatment follow-up period. Moreover, at the end of follow-up, the levels of surrogate cccDNA molecules in the livers of ccc_R08-treated HBVcircle mice were reduced to below the lower limit of quantification. CONCLUSIONS: We have discovered a small-molecule cccDNA inhibitor that reduces HBV cccDNA levels. cccDNA inhibitors potentially represent a new approach to completely cure patients chronically infected with HBV. IMPACT AND IMPLICATIONS: Covalently closed circular DNA (cccDNA) persistence in HBV-infected hepatocytes is the root cause of chronic hepatitis B. We discovered a novel small-molecule cccDNA inhibitor that can specifically reduce cccDNA levels in HBV-infected hepatocytes. This type of molecule could offer a new approach to completely cure patients chronically infected with HBV.

Stretchable and Self-Healable Fiber-Shaped Conductors Suitable for Harsh Environments.

Fiber-shaped conductors with high electrical conductivity, stretchability, and durability have attracted increasing attention due to their potential for integration into arbitrary wearable forms. However, these fiber conductors still suffer from low reliability and short life span, particularly in harsh environments. Herein, a conductive, environment-tolerant, stretchable, and healable fiber conductor (CESH), which consists of a self-healable and stretchable organohydrogel fiber core, a conductive and buckled silver nanowire coating, and a self-healable and waterproof protective sheath, is reported. Such a multilayer core-sheath design not only offers high stretchability (≈2400%), high electrical conductivity (1.0 × 106 S m-1 ), outstanding self-healing ability and durability, but also possesses unprecedented tolerance in harsh environments including wide working temperature (-60-20 °C), arid (≈10 % RH (RH: room humidity)), and underwater conditions. As proof-of-concept demonstrations, CESHs are integrated into various wearable formats as interconnectors to steadily perform the electric function under different mechanical deformations and harsh conditions. Such a new type of multifunctional fiber conductors can bridge the gap in stretchable and self-healing fiber technologies by providing ultrastable electrical conductance and excellent environmental tolerance, which can greatly expand the range of applications for fiber conductors.

Extraradical hyphae exhibit more plastic nutrient-acquisition strategies than roots under nitrogen enrichment in ectomycorrhiza-dominated forests.

Ectomycorrhizal (ECM) functional traits related to nutrient acquisition are impacted by nitrogen (N) deposition. However, less is known about whether these nutrient-acquisition traits associated with roots and hyphae differentially respond to increased N deposition in ECM-dominated forests with different initial N status. We conducted a chronic N addition experiment (25 kg N ha-1 year-1 ) in two ECM-dominated forests with contrasting initial N status, that is, a Pinus armandii forest (with relatively low N availability) and a Picea asperata forest (with relatively high N availability), to assess nutrient-mining and nutrient-foraging strategies associated with roots and hyphae under N addition. We show that nutrient-acquisition strategies of roots and hyphae differently respond to increased N addition. Root nutrient-acquisition strategies showed a consistent response to N addition, regardless of initial forest nutrient status, shifting from organic N mining toward inorganic N foraging. In contrast, the hyphal nutrient-acquisition strategy showed diverse responses to N addition depending on initial forest N status. In the Pinus armandii forest, trees increased belowground carbon (C) allocation to ECM fungi thus enhancing hyphal N-mining capacity under increased N availability. By comparison, in the Picea asperata forest, ECM fungi enhanced both capacities of P foraging and P mining in response to N-induced P limitation. In conclusion, our results demonstrate that ECM fungal hyphae exhibit greater plasticity in nutrient-mining and nutrient-foraging strategies than roots do in response to changes of nutrient status induced by N deposition. This study highlights the importance of ECM associations in tree acclimation and forest function stability under changing environments.

Proteomics profiling for the global and acetylated proteins of papillary thyroid cancers.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy cancer among the malignancies of thyroid. Despite of wide usages of proteomics in PTC, the profile of acetylated proteins in PTC remains unsettled, which is helpful for understanding the carcinogenesis mechanism and identifying useful biomarkers for PTC. METHODS: The surgically removed specimens of cancer tissues (Ca-T) and adjacent normal tissues (Ca-N) from 10 female patients pathological diagnosed as PTC (TNM stage III) were enrolled in the study. After preparing the pooled extracts of the whole proteins and the acetylated proteins from 10 cases, TMT labeling and LC/MS/MS methods were applied to the assays of global proteomics and acetylated proteomics separately. Bioinformatics analysis, including KEGG, gene ontology (GO) and hierarchical clustering were performed. Some differentially expressed proteins (DEPs) and differentially expressed acetylated proteins (DEAPs) were validated by individual Western blots. RESULTS: Controlled with the normal tissues adjacent to the lesions, 147 out of 1923 identified proteins in tumor tissues were considered as DEPs in global proteomics, including 78 up-regulated and 69 down-regulated ones, while 57 out of 311 identified acetylated proteins in tumor tissues were DEAPs in acetylated proteomics, including 32 up-regulated and 25 down-regulated, respectively. The top 3 up- and down-regulated DEPs were fibronectin 1, KRT1B protein and chitinase-3-like protein 1, as well as keratin, type I cytoskeletal 16, A-gamma globin Osilo variant and Huntingtin interacting protein-1. The top 3 up- and down-regulated DEAPs were ribosomal protein L18a-like protein, alpha-1-acid glycoprotein 2 and eukaryotic peptide chain release factor GTP-binding subunit ERF3A, as well as trefoil factor 3, thyroglobulin and histone H2B. Functional GO annotation and KEGG pathway analysis based on the DEPs and DEAPs showed completely different changing pictures. Contrary to the top 10 up- and -down regulated DEPs, most of which were addressed in PTC and other types of carcinomas, changes of the majority DEAPs were not mentioned in the literatures. CONCLUSIONS: Taken the profiling of the global and acetylated proteomics together will provide more broad view of protein alterations on the carcinogenesis and new direction for selecting biomarker for diagnosis of PTC.

Restoration Measures of Fencing after Tilling Guided Succession of Grassland Soil Microbial Community Structure to Natural Grassland in the Sanjiangyuan Agro-pasture Ecotone of the Qinghai-Tibetan Plateau.

In the fragile Sanjiangyuan (SJY) agro-pasture ecotone of the Qinghai-Tibetan Plateau (QTP), planting and fencing have been used to alleviate grassland degradation and to provide high-quality grass seeds for the implementation of the project of "grain for green". The soil microbe is the major driving factor in maintaining plant productivity and soil nutrient cycling. However, few studies have explored the effects of planting and fencing on soil microorganisms in the SJY agro-pasture ecotone. We explored the effects of tilling (TG) and fencing after tilling (FTG) on soil microbial communities to reveal the effects of restoration measures on soil microbes and to provide a reference in assessing and improving ecosystem structure. The results showed that restoration measures increased soil microbial species diversity and significantly changed their community structure. We found, the microbial composition was more complex under FTG, and its fungal variability was higher and more similar to that of natural grassland. Additionally, restoration measures resulted in fungal co-occurrence network was more edges, higher density, larger diameter and more positive interactions. This was due to the management of the vegetation-soil microenvironment by FTG inducing a differentiation of microbial community structure. In summary, the implementation of FTG could change the microenvironment in the SJY agro-pasture ecotone, so that variation in the structure of microbial community tended toward that of natural grassland, and increased the stability of microbial co-occurrence network, which was more obvious in the fungal community. HIGHLIGHTS: • Restoration measures have changed the vegetation characteristics and soil microenvironment. • Fencing after tilling (FTG) has brought the microenvironment closer to natural grassland. • FTG significantly increased microbial unique ASVs. The number of fungal unique ASVs was similar to that of natural grassland. • FTG resulted in changes in microbial community structure towards natural grasslands and increased the stability of the microbial co-occurrence network, which was more apparent in the fungal community.

Cold-Start NOx Mitigation by Passive Adsorption Using Pd-Exchanged Zeolites: From Material Design to Mechanism Understanding and System Integration.

It remains a major challenge to abate efficiently the harmful nitrogen oxides (NOx) in low-temperature diesel exhausts emitted during the cold-start period of engine operation. Passive NOx adsorbers (PNA), which could temporarily capture NOx at low temperatures (below 200 °C) and release the stored NOx at higher temperatures (normally 250-450 °C) to downstream selective catalytic reduction unit for complete abatement, hold promise to mitigate cold-start NOx emissions. In this review, recent advances in material design, mechanism understanding, and system integration are summarized for PNA based on palladium-exchanged zeolites. First, we discuss the choices of parent zeolite, Pd precursor, and synthetic method for the synthesis of Pd-zeolites with atomic Pd dispersions, and review the effect of hydrothermal aging on the properties and PNA performance of Pd-zeolites. Then, we show how different experimental and theoretical methodologies can be integrated to gain mechanistic insights into the nature of Pd active sites, the NOx storage/release chemistry, as well as the interactions between Pd and typical components/poisons in engine exhausts. This review also gathers several novel designs of PNA integration into modern exhaust after-treatment systems for practical application. At the end, we discuss the major challenges, as well as important implications, for the further development and real application of Pd-zeolite-based PNA in cold-start NOx mitigation.

Revealing the Formation and Reactivity of Cage-Confined Cu Pairs in Catalytic NOx Reduction over Cu-SSZ-13 Zeolites by In Situ UV-Vis Spectroscopy and Time-Dependent DFT Calculation.

The low-temperature mechanism of chabazite-type small-pore Cu-SSZ-13 zeolite, a state-of-the-art catalyst for ammonia-assisted selective reduction (NH3-SCR) of toxic NOx pollutants from heavy-duty vehicles, remains a debate and needs to be clarified for further improvement of NH3-SCR performance. In this study, we established experimental protocols to follow the dynamic redox cycling (i.e., CuII ↔ CuI) of Cu sites in Cu-SSZ-13 during low-temperature NH3-SCR catalysis by in situ ultraviolet-visible spectroscopy and in situ infrared spectroscopy. Further integrating the in situ spectroscopic observations with time-dependent density functional theory calculations allows us to identify two cage-confined transient states, namely, the O2-bridged Cu dimers (i.e., µ-η2:η2-peroxodiamino dicopper) and the proximately paired, chemically nonbonded CuI(NH3)2 sites, and to confirm the CuI(NH3)2 pair as a precursor to the O2-bridged Cu dimer. Comparative transient experiments reveal a particularly high reactivity of the CuI(NH3)2 pairs for NO-to-N2 reduction at low temperatures. Our study demonstrates direct experimental evidence for the transient formation and high reactivity of proximately paired CuI sites under zeolite confinement and provides new insights into the monomeric-to-dimeric Cu transformation for completing the Cu redox cycle in low-temperature NH3-SCR catalysis over Cu-SSZ-13.

Economical and Sustainable Synthesis of Small-Pore Chabazite Catalysts for NOx Abatement by Recycling Organic Structure-Directing Agents.

The application of small-pore chabazite-type SSZ-13 zeolites, key materials for the reduction of nitrogen oxides (NOx) in automotive exhausts and the selective conversion of methane, is limited by the use of expensive N,N,N-trimethyl-1-ammonium adamantine hydroxide (TMAdaOH) as an organic structure-directing agent (OSDA) during hydrothermal synthesis. Here, we report an economical and sustainable route for SSZ-13 synthesis by recycling and reusing the OSDA-containing waste liquids. The TMAdaOH concentration in waste liquids, determined by a bromocresol green colorimetric method, was found to be a key factor for SSZ-13 crystallization. The SSZ-13 zeolite synthesized under optimized conditions demonstrates similar physicochemical properties (surface area, porosity, crystallinity, Si/Al ratio, etc.) as that of the conventional synthetic approach. We then used the waste liquid-derived SSZ-13 as the parent zeolite to synthesize Cu ion-exchanged SSZ-13 (i.e., Cu-SSZ-13) for ammonia-mediated selective catalytic reduction of NOx (NH3-SCR) and observed a higher activity as well as better hydrothermal stability than Cu-SSZ-13 by conventional synthesis. In situ infrared and ultraviolet-visible spectroscopy investigations revealed that the superior NH3-SCR performance of waste liquid-derived Cu-SSZ-13 results from a higher density of Cu2+ sites coordinated to paired Al centers on the zeolite framework. The technoeconomic analysis highlights that recycling OSDA-containing waste liquids could reduce the raw material cost of SSZ-13 synthesis by 49.4% (mainly because of the higher utilization efficiency of TMAdaOH) and, meanwhile, the discharging of wastewater by 45.7%.

Engineering the Ultrasensitive Visual Whole-Cell Biosensors by Evolved MerR and 5' UTR for Detection of Ultratrace Mercury.

The existing mercury whole-cell biosensors (WCBs, parts per billion range) are not able to meet the real-world requirements due to their lack of sensitivity for the detection of ultratrace mercury in the environment. Ultratrace mercury is a potential threat to human health via the food chain. Here, we developed an ultrasensitive mercury WCB by directed evolution of the mercury-responsive transcriptional activator (MerR) sensing module to detect ultratrace mercury. Subsequently, the mutant WCB (m4-1) responding to mercury in the parts per trillion range after 1 h of induction was obtained. Its detection limit (LOD) was 0.313 ng/L, comparable to those of some analytical instruments. Surprisingly, the m4-1 WCB also responded to methylmercury (LOD = 98 ng/L), which is far more toxic than inorganic mercury. For more convenient detection, we have increased another green fluorescent protein reporter module with an optimized 5' untranslated region (5' UTR) sequence. This yields two visual WCBs with an enhanced fluorescence output. At a concentration of 2.5 ng/L, the fluorescence signals can be directly observed by the naked eye. With the combination of mobile phone imaging and image processing software, the 2GC WCB provided simple, rapid, and reliable quantitative and qualitative analysis of real samples (LOD = 0.307 ng/L). Taken together, these results indicate that the ultrasensitive visual whole-cell biosensors for ultratrace mercury detection are successfully designed using a combination of directed evolution and synthetic biotechnology.

Copper Site Motion Promotes Catalytic NOx Reduction under Zeolite Confinement.

Ammonia-mediated selective catalytic reduction (NH3-SCR) is currently the key approach to abate nitrogen oxides (NOx) emitted from heavy-duty lean-burn vehicles. The state-of-art NH3-SCR catalysts, namely, copper ion-exchanged chabazite (Cu-CHA) zeolites, perform rather poorly at low temperatures (below 200 °C) and are thus incapable of eliminating effectively NOx emissions under cold-start conditions. Here, we demonstrate a significant promotion of low-temperature NOx reduction by reinforcing the dynamic motion of zeolite-confined Cu sites during NH3-SCR. Combining complex impedance-based in situ spectroscopy (IS) and extended density-functional tight-binding molecular dynamics simulation, we revealed an environment- and temperature-dependent nature of the dynamic Cu motion within the zeolite lattice. Further coupling in situ IS with infrared spectroscopy allows us to unravel the critical role of monovalent Cu in the overall Cu mobility at a molecular level. Based on these mechanistic understandings, we elicit a boost of NOx reduction below 200 °C by reinforcing the dynamic Cu motion in various Cu-zeolites (Cu-CHA, Cu-ZSM-5, Cu-Beta, etc.) via facile postsynthesis treatments, either in a reductive mixture at low temperatures (below 250 °C) or in a nonoxidative atmosphere at high temperatures (above 450 °C).

A systematic review and meta-analysis of the effect of high-intensity statin on coronary microvascular dysfunction.

OBJECTIVE: The purpose of this meta-analysis is to evaluate the role of high-intensity statin pretreatment on coronary microvascular dysfunction in patients with coronary heart disease undergoing percutaneous coronary intervention (PCI). METHODS: PubMed, Cochrane, and Embase were searched. This meta-analysis selection included randomized controlled trials (RCTs), involving high-intensity statin pretreatment as active treatment, and measurement of thrombolysis in myocardial infarction (TIMI), myocardial blush grade (MBG) or index of microvascular resistance (IMR) in coronary heart disease (CHD) patients undergoing PCI. I2 test was used to evaluate heterogeneity. Pooled effects of continuous variables were reported as Standard mean difference (SMD) and 95% confidence intervals (CI). Pooled effects of discontinuous variables were reported as risk ratios (RR) and 95% confidence intervals (CI). Random-effect or fix-effect meta-analyses were performed. The Benefit was further examined based on clinical characteristics including diagnosis and statin type by using subgroup analyses. Publication bias was examined by quantitative Egger's test and funnel plot. We performed sensitivity analyses to examine the robustness of pooled effects. RESULTS: Twenty RCTs were enrolled. The data on TIMI < 3 was reported in 18 studies. Comparing with non-high-intensity statin, high-intensity statin pretreatment significantly improved TIMI after PCI (RR = 0.62, 95%CI: 0.50 to 0.78, P < 0.0001). The data on MBG < 2 was reported in 3 studies. The rate of MBG < 2 was not different between groups (RR = 1.29, 95% CI: 0.87 to 1.93, P = 0.21). The data on IMR was reported in 2 studies. High-dose statin pretreatment significantly improved IMR after PCI comparing with non-high-dose statin (SMD = -0.94, 95% CI: -1.47 to -0.42, P = 0.0004). There were no significant between-subgroup differences in subgroups based on statin type and diagnosis. Publication bias was not indicated by using quantitative Egger's test (P = 0.97) and funnel plot. Sensitivity analyses confirmed the robustness of these findings. CONCLUSIONS: Comparing with non-high-intensity statin, high-intensity statin pretreatment significantly improved TIMI and IMR after PCI. In the future, RCTs with high quality and large samples are needed to test these endpoints.

Association of waist-calf circumference ratio, waist circumference, calf circumference, and body mass index with all-cause and cause-specific mortality in older adults: a cohort study.

BACKGROUND: Waist circumference (WC), calf circumference (CC), and body mass index (BMI) have been independently linked to mortality. However, it's not yet clear how the waist-calf circumference ratio (WCR) relates to mortality. This study aims to investigate the relationship between WCR, WC, CC, and BMI with all-cause and cause-specific mortality in older adults. METHODS: In the 2014 Chinese Longitudinal Healthy Longevity Survey, 4627 participants aged 65 years and older were included, and they were subsequently followed up in 2018. Cox proportional hazards models were utilized to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality, based on WCR, WC, CC, and BMI. RESULTS: During a median follow-up of 3.4 years, 1671 deaths (36.1%) occurred. Compared to the second quartile of WCR, the highest quartile had a higher risk of mortality from all causes (HR 1.42, 95%CI 1.24-1.64), cardiovascular disease (CVD) (HR 1.88, 95%CI 1.38-2.56), and other causes (HR 1.37, 95%CI 1.15-1.63). The first and fourth quartiles of WC had HRs of 2.19 (1.00-4.79) and 2.69 (1.23-5.89), respectively, for cancer mortality. The highest quartile of CC was associated with a lower risk of all-cause and other-cause mortality, whereas the lowest quartile was associated with a higher risk of all-cause, CVD, and other-cause mortality compared to the second CC quartile. Additionally, the lowest quartile of BMI was associated with a higher risk of all-cause and respiratory disease mortality. Interaction analyses showed that the effects of CC on all-cause and CVD mortality were more pronounced in adults aged ≥ 80 years (P-interaction < .05). CONCLUSIONS: Higher WCR and lower CC increased the risk of all-cause, CVD, and other-cause mortality. Lower BMI was associated with higher all-cause and respiratory disease mortality risk, while WC only predicted cancer mortality.

Serum BLMH and CKM as Potential Biomarkers for Predicting Therapeutic Effects of Deep Brain Stimulation in Parkinson's Disease: A Proteomics Study.

BACKGROUND: Deep brain stimulation (DBS) is recommended for the treatment of advanced Parkinson's disease (PD), though individual reactions may be different. There are currently no clinically available biomarkers for predicting the responses of PD patients to DBS before surgery. This study aimed to determine serum biomarkers to predict DBS responses in PD. METHODS: We profiled differentially expressed proteins (DEPs) in serum samples and identified potential biomarkers to predict the therapeutic responses to DBS in PD patients. Ten serum samples were selected from PD patients to identify DEPs via mass spectrometry proteomics; these were then verified by enzyme-linked immunosorbent assay in another 21 serum samples of PD patients. RESULTS: The present study identified 14 DEPs (10 downregulated and four upregulated DEPs) with significantly different levels between non-responders and responders. Most of the DEPs were related to amino acid metabolism and protein modification pathways. Bleomycin hydrolase (BLMH) and creatine kinase M-type (CKM) were found to be significantly downregulated in the responders. Additionally, subsequent logistic regression and receiver operating characteristic analyses were performed to determine the diagnostic performance of candidate proteins. CONCLUSIONS: The identified DEPs show potential as biomarkers for the accurate evaluation of DBS therapeutic responses before surgery. Furthermore, assessment of serum BLMH and CKM may be particularly useful for predicting the therapeutic responses to DBS in PD patients.

Flexible and Robust Triboelectric Nanogenerators with Chemically Prepared Metal Electrodes and a Plastic Contact Interface Based on Low-Cost Pressure-Sensitive Adhesive.

Triboelectric nanogenerators (TENGs) are devices that can harvest energy from mechanical motions; such devices can be used to power wearable sensors and various low-power electronics. To increase the lifetime of the device, scientists mainly use the method of making TENG in a hard skeleton to simplify the complex possible relative movements between two triboelectric parts. However, the hard skeletons cannot be embedded in soft and lightweight clothing. To make matters worse, the materials used in the garments must be able to withstand high mechanical forces when worn, such as the pressure of more than 100 KPa exerted by body pressure or everyday knocks. Notably, the TENGs are usually made of fragile materials, such as vacuum-evaporated metal electrodes and nano-sized coatings, on the contact interface; these electrodes and coatings often chip or wear off under the action of external loads. In this work, we succeeded in creating a thin, light-weight, but extremely robust garment-integrated triboelectric nanogenerator (G-TENG) that can be embedded in clothing and pass the water wash test. First, we chemically deposited a durable electrode with flexible properties for G-TENG using a novel technique called polymer-assisted metal deposition (PAMD). The as-formed metal electrodes are firmly bonded to the plastic substrate by a sub-10 nm adhesive polymer brush and can withstand a pressure of 22.5 MPa and a tear force of 0.7 MPa. We then removed the traditionally used fragile nanoparticle materials and the non-durable poly-dimethylsiloxane (PDMS) layer at the triboelectric interface, and then used a cost-effective, durable and slightly flowable pressure-sensitive adhesive to form a plastic contact interface. Such a soft plastic interface can ensure full contact of the triboelectric materials, which is excellent in complex environments and ultimately improves the power generation efficiency of the devices. The as-formed low-cost energy harvesting device could become an industry standard for future smart clothing.

Epitaxial Integration of Multiple CdSe Quantum Dots in a Colloidal CdS Nanoplatelet.

Presynthesized CdSe/CdS core/shell quantum dots (QDs) are two-dimensionally (2D) and epitaxially fused in solution to form a CdS nanoplatelet with multiple epitaxially embedded CdSe QDs (CdSe@CdS coupled-dots@platelet). In addition to providing spatial confinement for the excitonic states of multiple CdSe QDs in a CdS nanoplatelet, the continuous and single-crystalline nanoplatelet with controlled thickness enables quantum coupling between the CdSe QDs, resulting in inhomogeneous-free optical properties for the colloidal CdSe@CdS coupled-dots@nanoplatelets with bright photoluminescence. The results here suggest that solution synthesis can offer a simple means to obtain semiconductor nanocrystals for realizing unique yet complex excitonic properties that are otherwise difficult to achieve.

Centromeric protein K (CENPK) promotes gastric cancer proliferation and migration via interacting with XRCC5.

BACKGROUND: CENPK is a novel oncogene which is aberrantly expression in some malignant tumors. However, the role and mechanisms of CENPK in gastric cancer have not been explored. METHODS: In this study, we use RT-PCR and IHC to study CENPK expression in gastric cancer cells and tissues. In addition, we constructed the two kinds of CENPK siRNA lentivirus to knock down CENPK. Then, we use High content living cell imaging System, Cell Counting Kit-8, colony formation, wound healing and Transwell assays to demonstrate the function of CENPK on gastric cancer cells AGS and MKN45. Meanwhile, we use flow cytometry assay to study CENPK function on gastric cancer cell apoptosis and cell cycle arrest. Subcutaneous tumorigenesis in nude mice was also performed to confirm CENPK function on gastric cancer. Finally, we use Co-IP, LC-MS and function rescue assay to study the downstream interaction molecular of CENPK. RESULTS: We demonstrated that CENPK expression were up-regulated in GC cell lines. Poor differentiation and III-IV stage had more percentages of high CENPK expression. Knocking down CENPK could significantly suppress GC cells proliferation, migration and invasion, and induce GC cells apoptosis and G1/S phase transition arrest. Subcutaneous tumorigenesis confirmed the tumor-promoting effects of CENPK in vivo. Remarkably, we found for the first time that XRCC5 might be interacted with CENPK through Co-IP, LC-MS and rescue study. CONCLUSION: CENPK promotes GC cell proliferation and migration via interacting with XRCC5 and may be a novel prognostic factor or therapeutic target for CENPK.