Search

Objective: Prescription opioid misuse and fatal overdoses have increased significantly over the last two decades. Living at altitude has been linked to greater reward benefits of other drugs of abuse, and living at altitude may also exacerbate the respiratory depression linked to opioid use. Therefore, we examined the relationships between living at altitude, and prescription opioid misuse and fatal overdoses. Method: State-level past year rates of prescription opioid misuse were retrieved from the Substance Abuse and Mental Health Services Administration. County-level overdose data were extracted from the Centers for Disease Control and Prevention. Multiple linear regression models were fit to determine the relationship between average state elevation and state rates of opioid misuse. Logistic regression models were fit to determine the relationship between county elevation and county-level fatal opioid overdose prevalence. Results: After controlling for state opioid prescribing rates and other confounders, we identified a significant positive association between mean state altitude and state-level opioid misuse rates for women, but not men. We also found a significant positive association between county-level altitude and prevalence of fatal opioid overdose. Conclusions: Living at altitude is thus demographically associated with increasing rates of misuse of prescription opioids, as well as of cocaine and methamphetamine. Animal studies suggest that the hypobaric hypoxia exposure involved with living at altitude may disrupt brain neurochemistry, to increase reward benefits of drugs of abuse. This increased misuse of both stimulants and opioids may increase likelihood of overdose at altitude, with overdoses by opioid use also potentially facilitated by altitude-related hypoxia. Keywords: Prescription opioids, Drug misuse, Opioid overdose, Hypobaric hypoxia, Altitude

Members of the phylum Bacteroidetes play a key role in the marine carbon cycle through their degradation of polysaccharides via carbohydrate-active enzymes (CAZymes) and polysaccharide utilization loci (PULs). The discovery of novel CAZymes and PULs is important for our understanding of the marine carbon cycle. In this study, we isolated and identified a potential new genus of the family Catalimonadaceae, in the phylum Bacteroidetes, from the southwest Indian Ocean. Strain TK19036, the type strain of the new genus, is predicted to encode CAZymes that are relatively abundant in marine Bacteroidetes genomes. Tunicatimonas pelagia NBRC 107804T, Porifericola rhodea NBRC 107748T and Catalinimonas niigatensis NBRC 109829T, which exhibit 16 S rRNA similarities exceeding 90% with strain TK19036, and belong to the same family, were selected as reference strains. These organisms possess a highly diverse repertoire of CAZymes and PULs, which may enable them to degrade a wide range of polysaccharides, especially pectin and alginate. In addition, some secretory CAZymes in strain TK19036 and its relatives were predicted to be transported by type IX secretion system (T9SS). Further, to the best of our knowledge, we propose the first reported “hybrid” PUL targeting alginates in T. pelagia NBRC 107804T. Our findings provide new insights into the polysaccharide degradation capacity of marine Bacteroidetes, and suggest that T9SS may play a more important role in this process than previously believed.

The stability of the stopping space is an important guarantee for the efficient and safe withdrawal of coal mining equipment. The influence of the position of the main roof fracture line on the stability of the surrounding rock in the stopping space was discussed, and the reasonable un-caving coal distance for the final mining stage of the working face was determined through discrete continuous coupling numerical simulation analysis. The instability interval of the key block of the main roof above stopping space was obtained by mechanical theory. The results showed that: (1) The reasonable stopping position of the working face in extra-thick coal seams was that the main roof fracture line was located behind supports (LLBS), and the reasonable un-caving distance of top coal was 10 m. (2) When the un-caving distance of top coal was 10 m, the load above key block was less than the critical load of sliding instability and rotary instability, and the voussoir beam structure was stable. (3) Asymmetric support scheme indicated that the support effect of the roof above the retraction channel was stronger than that of the roof above supports. The observation of underground pressure showed that the stopping space was effectively controlled.

The response of an anti-Compton phoswich detector to gamma rays was investigated using Monte-Carlo method, and the pulses from different crystal cases, including gamma deposition only in the LaBr3(Ce) or CsI(Tl) crystal and coincidence in both crystals, were analyzed. A novel pulse discrimination method for gamma deposition events based on wavelet transform analysis, called SSD (Scale Shape Discrimination), was developed in this study. Compared to the traditional PSD (Pulse Shape Discrimination) method, SSD has the advantage of transforming one-dimensional pulses in the time-domain into two-dimensional time-frequency spectra, providing the more useful features for pulse discrimination. The performances of the Compton suppression and Full-energy peak loss using PSD and SSD methods was studied. The results show that the Compton suppression factor IPSD = 5.12 and ISSD = 5.32, and FEP loss factor PLPSD = 0.0554 and PLSSD = 0.0587. Meanwhile, the influences of the cutoff values for pulse discrimination on the results of I and PL with different method were analyzed.

In current electronic structure research endeavors such as warm dense matter or machine learning applications, efficient development necessitates non-monolithic software, providing an extendable and flexible interface. The open-source idea offers the advantage of having a source code base that can be reviewed and modified by the community. However, practical implementations can often diverge significantly from their theoretical counterpart. Leveraging the efforts of recent theoretical formulations and the features of Python, we try to mitigate these problems. We present eminus, an education- and development-friendly electronic structure package designed for convenient and customizable workflows, yet built with intelligible and modular implementations.

Background: Exposure to brominated flame retardants (BFRs) may negatively impact human health. The association of BFRs with nonalcoholic fatty liver disease (NAFLD) in the general population is unclear. Meanwhile, limited studies have investigated the potential role of oxidative stress and inflammation in this link. Methods: We included 4110 adults from the 2009–2014 National Health and Nutrition Examination Survey (NHANES). NAFLD was diagnosed by serum alanine aminotransferase (ALT), hepatic steatosis index (HSI), and United States fatty liver index (USFLI). The link between a single BFR exposure and NAFLD was estimated using weighted logistic regression and restricted cubic splines (RCS). The quantile-based g-computation (QGC), weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) were applied to evaluate the overall correlation of BFRs mixtures with NAFLD and identify significant compounds. Furthermore, we investigated the potential mediation function of oxidative stress and inflammation. Results: Our study demonstrated that specific concentrations of BFRs are related to an increased risk of NAFLD, both individually and when combined. PBB153, PBDE28, PBDE209, and PBDE153 exhibited the highest importance for NAFLD and were potential risk factors worthy of concern. Additionally, mediation analysis showed that absolute neutrophil cell count (ANC) and lymphocyte count (LC) (inflammation markers) have significantly mediated influences on the correlations of PBB153, PBDE85, and PBDE28 with N AFLD risk. Albumin (ALB) (oxidative stress marker) has notably mediated influences on the correlations of PBDE99, PBDE154, and PBDE85 with NAFLD risk. Men had higher serum BFRs concentrations than women, and the association between BFRs and NAFLD was also more prominent in men, which may be related to physiological differences between the sexes. Conclusions: Our findings offer evidence for single and mixed associations of BFRs and NAFLD in ordinary US adults. Furthermore, oxidative stress and chronic inflammation may mediate the effects of BFR exposure on NAFLD development.

Piezoelectric micromachined ultrasonic transducers (p-MUTs) have been extensively utilized in medical imaging, range-finding, gesture recognition, and so on. However, the piezoelectric layer is dominated by the toxic Pb(Zr, Ti)O3, other materials possess inferior piezoelectric coefficients, and the traditional clamped diaphragm restricts the p-MUT response. In this work, lead-free ZnO films are doped by the vanadium nanostructures and are implemented to beam-island structure membranes, which are aimed to achieve non-toxic and high-performance p-MUTs. Firstly, the doping mechanism of ZnO is analyzed and the p-MUT structure is designed. Secondly, simulation based on the finite element method is conducted to evaluate the dynamic displacement of p-MUTs, after which prototypes are fabricated by the standard micromachined process. The effects of key fabrication parameters including O2 flow rates, sputtering targets, and annealing temperatures on V-doped ZnO films are investigated in detail. By using atomic force microscopy (AFM) and X-ray diffraction (XRD), the surface morphology and crystal structure of the films are analyzed respectively. Moreover, the piezoelectric properties are measured by piezo response force microscopy (PFM). The results indicate a piezoelectric coefficient as high as 194.5 pm/V, which is superior to most doped ZnO films. Finally, an experimental testing system is established to examine the p-MUT performance. Compared with the clamped diaphragm, the beam-island structure can acquire better electromechanical coupling and achieve range-finding successfully. This work provides a fine application prospect for enhancing the performance of lead-free p-MUTs.

Addressing the dual environmental challenges of dredged sludge disposal and the repurposing of industrial by-products, this study pioneers the application of Calcium Carbide Residue (CCR)-based materials for stabilizing dredged sludge in road subgrade construction. The proliferation of dredged sludge, characterized by high moisture content and pollutants, presents a significant environmental hazard, while CCR, a by-product of acetylene production, poses disposal and pollution challenges. This research endeavors to mitigate these issues by exploring the stabilization potential of CCR when mixed with dredged sludge, aiming to enhance the mechanical properties of materials used in road subgrade construction. Through comprehensive laboratory testing, including unconfined compressive strength assessments, scanning electron microscope analyses, and X-ray diffraction examinations, the study reveals the intricate physicochemical interactions between CCR and sludge. These interactions lead to notable improvements in material strength and moisture reduction, substantiating the efficacy of CCR-based binders in sludge stabilization. The CCR-based binder can make the strength of the stabilized sludge reach 215.4kPa and the water content drop to 32 %. Field tests conducted to assess real-world applicability confirm the laboratory results, demonstrating the treated material's suitability for road construction as per secondary road design criteria and its environmental safety. The research highlights the environmental and engineering benefits of using CCR-based materials for sludge stabilization, offering a sustainable solution to the challenges of dredged sludge management and industrial waste utilization. The findings represent a step forward in waste-to-resource conversion, promoting environmental sustainability in civil engineering practices.

Background & Aims: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death. Metabolic dysfunction-associated steatotic liver disease (MASLD) is a significant cause of HCC. Current treatment options for HCC are very limited. Recent evidence highlights B cells as key drivers in MASLD progression toward HCC. However, it remains unclear whether multiple B cell populations or a distinct B cell subset regulates inflammatory responses during liver disease progression. The scope of this study was to define protumorigenic B cell subsets in MASLD and HCC. Methods: Multicolor flow cytometry, immunohistochemistry, and immunofluorescence analyses were performed to investigate B cell populations locally (in liver tissue) and systemically (in the blood) in mice with MASLD (n = 6) and HCC (n = 5–6). The results obtained in mice were also verified in patients with MASLD (n = 19) and HCC (n = 16). Results: Our study revealed an increase of two regulatory B cell (Breg) subsets, CD19+B220+CD5+CD1d+ (p

Recent advances in cognitive neuroscience have focused on using resting-state functional connectivity (RSFC) data from fMRI scans to more accurately predict human traits and behaviors. Traditional approaches generally analyze RSFC by correlating averaged time-series data across regions of interest (ROIs) or networks, which may overlook important spatial signal patterns. To address this limitation, we introduced a novel linear regression technique that estimates RSFC by predicting spatial brain activity patterns in a target ROI from those in a seed ROI. We applied both traditional and our novel RSFC estimation methods to a large-scale dataset from the Human Connectome Project and the Brain Genomics Superstruct Project, analyzing resting-state fMRI data to predict sex, age, personality traits, and psychological task performance. To enhance prediction accuracy, we developed an ensemble learner that combines these qualitatively different methods using a weighted average approach. Our findings revealed that hierarchical clustering of RSFC patterns using our novel method displays distinct whole-brain grouping patterns compared to the traditional approach. Importantly, the ensemble model, integrating these diverse weak learners, outperformed the traditional RSFC method in predicting human traits and behaviors. Notably, the predictions from the traditional and novel methods showed relatively low similarity, indicating that our novel approach captures unique and previously undetected information about human traits and behaviors through fine-grained local spatial patterns of neural activation. These results highlight the potential of combining traditional and innovative RSFC analysis techniques to enrich our understanding of the neural basis of human traits and behaviors.

Src homology-2-containing protein tyrosine phosphatase 2 (SHP2) is a promising therapeutic target for cancer therapy. In this work, we presented the structure-guided design of 5,6-fused bicyclic allosteric SHP2 inhibitors, leading to the identification of pyrazolopyrazine-based TK-642 as a highly potent, selective, orally bioavailable allosteric SHP2 inhibitor (SHP2WT IC50 = 2.7 nmol/L) with favorable pharmacokinetic profiles (F = 42.5%; t1/2 = 2.47 h). Both dual inhibition biochemical assay and docking analysis indicated that TK-642 likely bound to the “tunnel” allosteric site of SHP2. TK-642 could effectively suppress cell proliferation (KYSE-520 cells IC50 = 5.73 μmol/L) and induce apoptosis in esophageal cancer cells by targeting the SHP2-mediated AKT and ERK signaling pathways. Additionally, oral administration of TK-642 also demonstrated effective anti-tumor effects in the KYSE-520 xenograft mouse model, with a T/C value of 83.69%. Collectively, TK-642 may warrant further investigation as a promising lead compound for the treatment of esophageal cancer.

The advantages of on-chip integrated photodetectors, such as miniaturization, high integration, and reliability, make them an indispensable and important part of electronic devices and systems. Herein, we experimentally exhibited a monolithically integrated ultraviolet photodetector utilizing GaN microcylinder epitaxial structure on Si wafer, with its photoresponse properties plasmonically boosted using Pt nanoparticles via specific sizes. When illuminated upon ultraviolet light at 0 V bias, the Pt/GaN device exhibits significant photovoltaic performances, including a peak responsivity of 200.1 mA W−1, external quantum efficiency of 65%, and other figures-of-merit. Finite element analysis and energy band theory confirm that the excellent photodetection properties of the Pt/GaN device are related to the strong plasmon absorption and the increase of hot electrons injected into the GaN conduction band, which considerably improves its photoresponse performance and robustness in application. To realize the multipurpose capability of the devices, we validated the application of Pt/GaN as turbidity sensing and achieved a resolution of up to 100 NTU. Moreover, the prepared devices can be used as optical data receivers for optical communication. These findings provide references for on-chip detectors to improve the overall system performance and promote the realization of more complex applications.

Quantifying the contribution and modes of action of climate variation and vegetation greening to evapotranspiration (ET) and water yield (WY) in the growing season of the Yanhe River Watershed (YHRW) is of great significance for scientifically managing the ecosystem in water-scarce areas. This study simulated the ET of YHRW based on the Eagleson model and analyzed the contribution, direct and indirect effects of climate variables (including precipitation (Pre), temperature (Tem), radiation (RN), relative humidity (RH), wind speed (Wind)) and vegetation on the ET and WY changes during three time periods of YHRW. The results suggested the ET in the YHRW mainly showed a downward trend from 1982 to 1999, and it turned into an increasing trend after 1999. From 1982 to 2018, ET showed an overall upward trend (2.02 mm·year−1), while WY in three different study periods mainly showed a decreasing trend. Spatially, RN, Tem, and Wind were the drivers controlling ET and WY changes from 1982 to 1999. After 1999, LAI was the main controller in ET changes, while climate factors were the main contributors to WY changes. During the 1982–2018 research period, vegetation had the greatest impact on regional ET changes, while Pre dominated the WY changes. The effects of climate variation and vegetation greening on ET and WY are complex and non-independent. Tem and RH are key mediations of ET variation, while Tem and RH are key mediating factors in WY variation. We emphasize the spatial heterogeneity in water budget changes during the vegetation growth period of YHRW at different time periods, especially after large-scale vegetation greening. This finding should be considered in the planning of sustainable development in water-scarce areas in the future to make the local eco-hydrological effect the best.

Background: Mechanisms of synaptic plasticity in retinal ganglion cells (RGCs) are complex and the current knowledge cannot explain. Growth and regeneration of dendrites together with synaptic formation are the most important parameters for evaluating the cellular protective effects of various molecules. The effect of ginsenoside Rg1 (Rg1) on the growth of retinal ganglion cell processes has been poorly understood. Therefore, we investigated the effect of ginsenoside Rg1 on the neurite growth of RGCs. Methods: Expression of proteins and mRNA were detected by Western blot and qPCR. cAMP levels were determined by ELISA. In vivo effects of Rg1 on RGCs were evaluated by hematoxylin and eosin, and immunohistochemistry staining. Results: This study found that Rg1 promoted the growth and synaptic plasticity of RGCs neurite by activating the cAMP/PKA/CREB pathways. Meanwhile, Rg1 upregulated the expression of GAP43, Rac1 and PAX6, which are closely related to the growth of neurons. Meantime, H89, an antagonist of PKA, could block this effect of Rg1. In addition, we preliminarily explored the effect of Rg1 on enhancing the glycolysis of RGCs, which could be one of the mechanisms for its neuroprotective effects. Conclusion: Rg1 promoted neurite growth of RGCs through cAMP/PKA/CREB pathways. This study may lay a foundation for its clinical use of optic nerve diseases in the future.

Bisphenol A (BPA) is a growing concern as an endocrine-disrupting chemical due to its adverse health effects. However, the association between BPA and sperm quality in adult human males remains unclear. The aim of this study was to assess the daily life exposure level of BPA and analyze its correlation with sperm quality in males. Patients who sought treatment in Chinese infertility clinics between May and October 2023 were selected as study subjects. We determined participants' serum BPA content using high-performance liquid chromatography. Sperm count and motility were assessed using a computer-aided sperm analysis system, while sperm morphology was analyzed using an improved Papanicolaou stain. A total of 405 participants, averaging 33.01 ± 5.44 years old, were included. We observed low semen quality among participants in infertility clinics. Principal component analysis was performed for each semen quality index, and three principal components reflecting sperm motility, count, and morphology were extracted. The participants' mean serum BPA level was 6.96 ng/mL. Negative correlations were observed between serum BPA content and total sperm count, sperm density, forward motility rate, and non-forward motility rate. A positive correlation was found between the non-motile sperm rate and the head deformity rate. Morphological abnormalities were the predominant adverse effects observed. Despite low daily life BPA exposure, long-term low-dose exposure in the general population may damage semen quality. This study provides a scientific basis for managing health risks associated with BPA exposure.

Quantitatively investigating and assessing the spatiotemporal variation in the human activity intensity (HAI) and its influencing factors are crucial for coordinating regional human–land relationships and protecting the eco-environment. However, the scale, variation pattern, and driving factors of the human activity intensity in the Guangxi Beibu Gulf Zone have not yet been determined. To bridge this gap, this study focused on evaluating and analyzing the spatiotemporal variation characteristics of the HAI from 2000 to 2020 by a quantitative model based on multi-period land use data, field survey data, and statistical data. Moreover, the socioeconomic and geographical determinants were investigated using the PCA method and Geodetector model. The results showed that (1) the overall HAI value was relatively high and increased from 18.97% in 2000 to 20.06% in 2020. The HAI value in Haicheng District was always the highest and peaked at 60.78% in 2020. (2) Spatially, approximately 19.88% of the area exhibited high HAI values, and these areas were mainly distributed in urban districts, county seats, towns, and farming areas. In contrast, the areas with low HAI values were mainly concentrated in mountainous areas and natural reserves. (3) The HAI exhibited a significant spatial agglomeration effect, and HAI hot spots were concentrated mainly in areas with intense change, such as economic development zones, industrial parks, urban suburbs, and towns with added counties. (4) The HAI was affected by various influencing factors, and the explanatory power of multiple factors for the HAI change was greater than that of a single factor.

Aims: To investigate the prognostic accuracy of a non-medical generative artificial intelligence model (Chat Generative Pre-Trained Transformer 4 - ChatGPT-4) as a novel aspect in predicting death and poor neurological outcome at hospital discharge based on real-life data from cardiac arrest patients. Methods: This prospective cohort study investigates the prognostic performance of ChatGPT-4 to predict outcomes at hospital discharge of adult cardiac arrest patients admitted to intensive care at a large Swiss tertiary academic medical center (COMMUNICATE/PROPHETIC cohort study). We prompted ChatGPT-4 with sixteen prognostic parameters derived from established post-cardiac arrest scores for each patient. We compared the prognostic performance of ChatGPT-4 regarding the area under the curve (AUC), sensitivity, specificity, positive and negative predictive values, and likelihood ratios of three cardiac arrest scores (Out-of-Hospital Cardiac Arrest [OHCA], Cardiac Arrest Hospital Prognosis [CAHP], and PROgnostication using LOGistic regression model for Unselected adult cardiac arrest patients in the Early stages [PROLOGUE score]) for in-hospital mortality and poor neurological outcome. Results: Mortality at hospital discharge was 43% (n = 309/713), 54% of patients (n = 387/713) had a poor neurological outcome. ChatGPT-4 showed good discrimination regarding in-hospital mortality with an AUC of 0.85, similar to the OHCA, CAHP, and PROLOGUE (AUCs of 0.82, 0.83, and 0.84, respectively) scores. For poor neurological outcome, ChatGPT-4 showed a similar prediction to the post-cardiac arrest scores (AUC 0.83). Conclusions: ChatGPT-4 showed a similar performance in predicting mortality and poor neurological outcome compared to validated post-cardiac arrest scores. However, more research is needed regarding illogical answers for potential incorporation of an LLM in the multimodal outcome prognostication after cardiac arrest.

Summary: Drug efflux transporters are a major determinant of drug efficacy and toxicity. A canonical example is P-glycoprotein (P-gp), an efflux transporter that controls the intestinal absorption of diverse compounds. Despite a rich literature on the dietary and pharmaceutical compounds that impact P-gp activity, its sensitivity to gut microbial metabolites remains an open question. Surprisingly, we found that the cardiac drug-metabolizing gut Actinobacterium Eggerthella lenta increases drug absorption in mice. Experiments in cell culture revealed that E. lenta produces a soluble factor that post-translationally inhibits P-gp ATPase efflux activity. P-gp inhibition is conserved in the Eggerthellaceae family but absent in other Actinobacteria. Comparative genomics identified genes associated with P-gp inhibition. Finally, activity-guided biochemical fractionation coupled to metabolomics implicated a group of small polar metabolites with P-gp inhibitory activity. These results highlight the importance of considering the broader relevance of the gut microbiome for drug disposition beyond first-pass metabolism.

Objective: Aneurysms occurring in the ophthalmic segment (C6) of the internal carotid artery (ICA) have complex anatomy. This poses a challenge for the use of traditional open surgery, which is gradually being replaced by endovascular treatment (EVT). However, multiple aneurysm (MA) EVT, especially in MAs occurring ipsilaterally, has not been specifically described or discussed. The present study aimed to propose a more concise clinical classification standard for ipsilateral C6 ICA MAs and report on the clinical experience with EVT. Methods: The cases of 18 patients with ipsilateral C6 ICA MAs treated with EVT were retrospectively reviewed. The treatment results and procedure-related complications were recorded, and clinical and angiographic follow-ups were performed at least six months after surgery. Results: A total of 38 ipsilateral C6 ICA aneurysms were treated during the study period and classified into four main types and six total subtypes based on anatomical features. There was a failure to coil through the stent in one aneurysm, while the remaining 37 were successfully treated using various EVT methods. Of these, 36 were completely concluded. One aneurysm had a size reduction, and one had no changes during the angiographic follow-up. All Tubridge flow diverter stents were patent. All patients achieved satisfactory clinical outcomes and were independent at the final follow-up. Conclusion: EVT may be safe and feasible for the treatment of C6 ICA MAs. Traditional stent-assisted coiling methods, the Willis covered stent, and the double-layered low-profile visualized intraluminal support stent all achieved favorable results. The flow diverter stent is also considered a safe and efficient option for selected aneurysms, but the visual deficit risk should be considered. The present study introduces a new EVT classification option based on the anatomical features of an aneurysm.

In the pursuit of simultaneously improving the yield strength and plasticity of austenitic stainless steel, a new austenitic stainless steel was fabricated by induction smelting using a pure N2 atmosphere, hot forging, cryogenic rolling, and annealing. The material was characterized by microstructures with 3–4 μm uniform finer grains, fine precipitates, high thermal stability austenite, and extensive high-angle grain boundaries. The elongation after fracture, yield strength, and ultimate tensile strength of the samples reached 53.5 %, 707 MPa, and 1020 MPa, respectively, as well as 61 %, 600 MPa, and 977 MPa, respectively, at the same time. Moreover, a high strain hardening rate was achieved in the new stainless steel. The appropriate uniform finer grains not only played a role in grain-refined strengthening but also provided intragranular spaces and sufficient mean free available paths for dislocation accumulation and movement. Precipitates, which were coherent or semi-coherent with the matrix, provided interfaces for dislocation accumulation and obstructions for dislocation movement. Extensive high-angle grain boundaries with appropriate finer grains served as another important factor for excellent ductility due to the inhabitation and resulting deviation of crack propagation. In addition, strain-induced mechanical twinning in the current austenitic stainless steel contributed to excellent ductility and high strength.

Aims: To assess the DNR preferences of critical care-, anesthesia- and emergency medicine practitioners, to identify factors influencing decision-making, and to raise awareness for misconceptions concerning CPR outcomes. Methods: A nationwide multicenter survey was conducted in Switzerland confronting healthcare professionals with a case vignette of an adult patient with an out-of-hospital cardiac arrest (OHCA). The primary outcome was the rate of DNR Code Status vs. CPR Code Status when taking the perspective from a clinical case vignette of a 70-year-old patient. Secondary outcomes were participants’ personal preferences for DNR and estimates of survival with good neurological outcome after in- and out-of-hospital cardiac arrest. Results: Within 1803 healthcare professionals, DNR code status was preferred in 85% (n = 1532) in the personal perspective of the case vignette and 53.2% (n = 932) when making a decision for themselves. Main predictors for a DNR Code Status regarding the case vignette included preferences for DNR Code Status for themselves (n [%] 896 [58.5] vs. 87 [32.1]; adjusted odds ratio [OR] 2.97, 95% confidence interval [CI] 2.25–3.92; p

Background and aim: Recent studies show that combination of apoptosis and oxidative stress forms a “vicious circle” in the process of premature ovarian failure (POF). Pearl extract has a good effect for anti-oxidation and anti-aging in vitro and vivo and can be used to treat various aging diseases. However, reports about effect and mechanism of pearl on ovarian function of premature ovarian failure (POF)are limited. Experimental procedure: The effect and mechanism of pearl on ovarian function of rats with POF were evaluated using rats with premature ovarian failure induced by tripterygium glycosides. The estrous cycle, contents of serum reproductive hormones, tissue structure, oxidative stress level, autophagy and apoptotic protein expression, and MAPK signaling pathway of ovary were assessed to characterise pearl. Result and conclusion: Low, medium and high-dose pearl improved the estrous cycle in POF rats, and high-dose pearl was the best in terms of recovery effect; high-dose pearl significantly increased (P

NiTi shape memory alloy (SMA) has been suggested as an environmentally friendly solid-state refrigerant that is expected to replace the traditional vapor compression technology. However, its various refrigeration indicators still need to be further explored and enhanced. Nanocrystalline NiTi SMA has significant advantages in terms of elastocaloric effect (eCE) and cyclic stability compared with traditional coarse-grained NiTi SMA. In this work, the influence of aspect ratio (L/W, where L and W are the gauge length and width of the samples, respectively) on the eCE and its cyclic stability of nanocrystalline NiTi SMA was investigated experimentally. The in-situ cyclic tensile tests were performed to observe the axial strain field and temperature field on the surface of the specimens with different aspect ratios. Some microscopic observations were also carried out to clarify the internal mechanism. The experimental results show that as the aspect ratio decreases, the adiabatic temperature change ΔTad (elasocaloric cooling capacity) of the nanocrystalline NiTi SMA gradually decreases, while the coefficient of the performance of material (COPmat) increases, and the cyclic stability of eCE was enhanced. However, the dependence of eCE and its cyclic stability on the aspect ratio is gradually weakened when L/W > 4. The eCE and its cyclic stability of nanocrystalline NiTi SMA are not related to the dislocation slipping but rather attributed to the cyclically accumulated residual martensite. This work can provide valuable reference for designing efficient and reliable nanocrystalline NiTi SMA based solid-state refrigeration devices.

The design of new ligands with high affinity and specificity against the targets of interest has been a central focus in drug discovery. As one of the most commonly used methods in drug discovery, the cyclization represents a feasible strategy to identify new lead compounds by increasing structural novelty, scaffold diversity and complexity. Such strategy could also be potentially used for the follow-on drug discovery without patent infringement. In recent years, the cyclization strategy has witnessed great success in the discovery of new lead compounds against different targets for treating various diseases. Herein, we first briefly summarize the use of the cyclization strategy in the discovery of new small-molecule lead compounds, including the proteolysis targeting chimeras (PROTAC) molecules. Particularly, we focus on four main strategies including fused ring cyclization, chain cyclization, spirocyclization and macrocyclization and highlight the use of the cyclization strategy in lead generation. Finally, the challenges including the synthetic intractability, relatively poor pharmacokinetics (PK) profiles and the absence of the structural information for rational structure-based cyclization are also briefly discussed. We hope this review, not exhaustive, could provide a timely overview on the cyclization strategy for the discovery of new lead compounds.

This paper presents numerical simulation of graphe nanoplatelet (GNP) – sodium dodecylbenzene sulfonate (SDBS) – water nanofluid with volumetric mass fractions of ϕ equal to 0–0.1%. The new microchannel is made of 2 layers and has sinusoidal cavities along with the heat sink. The study was conducted for Re = 50, 300, 700 and 1000 (laminar flow). Based on the results, higher Re leads to more convective heat transfer coefficient. Therefore, the value of temperature gradients decreases and on the other hand the effect of cooling fluid temperature in warm areas near solid wall becomes important. Using a higher value of Re results in the penetration of heat in the fluid layer decreases which in general will reduce the temperature of the outlet section in larger Re values. Also, larger Re value results in larger development length which is also a cause for lack of thermal development and dominance of the temperature of the coolant flow in the heat sink resulting in decreased outlet section temperature for higher Reynolds numbers. For Re = 50 and 300 because of lower fluid velocity, the effect of surface geometry factors such as sinusoidal paths or hollow parts (cavities) has a smaller influence on the pressure loss or friction factor of the flow.

To study the open collaborative innovation path optimization of urban agglomeration energy industry based on particle swarm optimization algorithm. Firstly, this paper brings industrial agglomeration and urban agglomeration into a unified analytical framework, uses location entropy and spatial Gini coefficient to measure the degree of industrial agglomeration, and evaluates the degree of regional industrial agglomeration competitiveness by constructing an evaluation index system of industrial agglomeration competitiveness. Then, the agglomeration index system was established, the development degree analysis method and Carlino model were used to analyze the development degree and agglomeration degree of eco-economic zones, and the agglomeration effect was analyzed by dynamic econometric method and spatial autocorrelation statistical method. Finally, a regional collaborative innovation capability evaluation model based on particle swarm optimization algorithm is constructed. Based on the index system and evaluation model, this paper evaluates and analyzes the collaborative innovation capability, and puts forward countermeasures and suggestions for future collaborative development.

With the rapid development of international energy trade, its structure has shown a trend toward complexity and network development. The traditional unilateral or bilateral perspective of causal analysis can no longer explain the changes in the international energy trade network at this stage. This paper constructs the world energy trade network from 2000 to 2020, analyzes the structural characteristics of the network, and adopts the quadratic assignment procedure method to deconstruct and explain the structural evolution of the world energy trade network. The study shows that the global energy trade network is increasingly connected and has small-world characteristics; the growing global energy demand coexists with the increasing energy monopoly; GDP difference and geographical distance are the decisive factors in forming an international energy trade network. It is suggested that countries should strengthen the integrated development of energy trade; formulate differentiated regional policies according to the structure and economic development characteristics of national and regional energy trade; pay more attention to the hub vertexes in the international energy trade network; and formulate differentiated energy strategies for countries and regions with different development levels, taking into account their development situations.

Summary: RNA polymerase III (Pol III) plays a vital role in transcription and as a viral-DNA sensor, but how it is assembled and distributed within cells remains poorly understood. Here, we show that Pol III is assembled with chaperones in the cytoplasm and forms transcription-dependent protein clusters upon transport into the nucleus. The largest subunit (RPC1) depletion through an auxin-inducible degron leads to rapid degradation and disassembly of Pol III complex in the nucleus and cytoplasm, respectively. This generates a pool of partially assembled Pol III intermediates, which can be rapidly mobilized into the nucleus upon the restoration of RPC1. Our study highlights the critical role of subcellular localization in determining Pol III’s fate and provides insight into the dynamic regulation of nuclear Pol III levels and the origin of cytoplasmic Pol III complexes involved in mediating viral immunity.

AIMS: To assess the do-not-resuscitate preferences of the general Swiss population and to identify predictors influencing decision-making. Methods: A nationwide web-based survey was conducted in Switzerland on a representative sample of the adult population. The primary endpoint was the preference for a “Do Not Resuscitate” order (DNR Code Status) vs. cardiopulmonary resuscitation (CPR Code Status) in a clinical case vignette of an out-of-hospital cardiac arrest. Secondary endpoint were participants’ own personal preferences for DNR. Results: 1138 subjects participated in the web-based survey, 1044 were included in the final analysis. Preference for DNR code status was found in 40.5% (n = 423) in the case vignette and in 20.3% (n = 209) when making a personal decision for themselves. Independent predictors for DNR Code Status for the case vignette were: Personal preferences for their own DNR Code Status (adjusted OR 2.44, 95%CI 1.67 to 3.55; p

The ternary chalcogenide MnPSe3 monolayer recently gets a lot of attention because of its two nonequivalent energy valleys. The existence of spin–orbit coupling (SOC) effect can cause the valley splitting of around 24 meV. However, the spin degeneracy is still kept in MnPSe3 monolayer owing to the antiferromagnetic coupling between Mn2+ ions. The interlayer coupling effect in the van der Waals (vdW) heterostructures can break the symmetry of MnPSe3 and induce the spin splitting. Here, we simulate the MnPSe3/GeC vdW heterostructure and investigate the effects of the stacking and interlayer coupling effect on both spin and valley splitting. The excitation mode of valley excitons is greatly related to the stacking of heterostructures. The interlayer excitons can only be formed in one of the configurations with C3 symmetry according to optical selection transition rule. The interlayer coupling effect is modulated by changing interlayer distance. With vertical compressive strain (−20%), the spin and valley splitting higher than 50 meV and 30 meV can be obtained in MnPSe3/GeC vdW heterostructures, respectively. This study suggests that the stacking and vertical strain are both efficient approaches to modulate the spin and valley splitting through the interlayer coupling effect in the vdW heterostructures.

Objectives: To determine the role of MYL4 regulation of lysosomal function and its disturbance in fibrotic atrial cardiomyopathy. Background: We have previously demonstrated that the atrial-specific essential light chain protein MYL4 is required for atrial contractile, electrical, and structural integrity. MYL4 mutation/dysfunction leads to atrial fibrosis, standstill, and dysrhythmia. However, the underlying pathogenic mechanisms remain unclear. Methods and results: Rats subjected to knock-in of a pathogenic MYL4 mutant (p.E11K) developed fibrotic atrial cardiomyopathy. Proteome analysis and single-cell RNA sequencing indicate enrichment of autophagy pathways in mutant-MYL4 atrial dysfunction. Immunofluorescence and electron microscopy revealed undegraded autophagic vesicles accumulated in MYL4p.E11K rat atrium. Next, we identified that dysfunctional MYL4 protein impairs autophagy flux in vitro and in vivo. Cardiac lysosome positioning and mobility were regulated by MYL4 in cardiomyocytes, which affected lysosomal acidification and maturation of lysosomal cathepsins. We then examined the effects of MYL4 overexpression via adenoviral gene-transfer on atrial cardiomyopathy induced by MYL4 mutation: MYL4 protein overexpression attenuated atrial structural remodeling and autophagy dysfunction. Conclusions: MYL4 regulates autophagic flux in atrial cardiomyocytes via lysosomal mobility. MYL4 overexpression attenuates MYL4 p.E11K induced fibrotic atrial cardiomyopathy, while correcting autophagy and lysosomal function. These results provide a molecular basis for MYL4-mutant induced fibrotic atrial cardiomyopathy and identify a potential biological-therapy approach for the treatment of atrial fibrosis.

In the present study, we studied the effect of high oxygen-modified packaging (HiOx-MAP) on yak meat tenderness and the underlying mechanism. HiOx-MAP significantly increased the myofibril fragmentation index (MFI) of yak meat. In addition, western blotting showed that the expression of hypoxia-inducible factor (HIF-1α) and ryanodine receptors (RyR) in the HiOx-MAP group was reduced. HiOx-MAP increased the activity of sarcoplasmic reticulum calcium-ATPase (SERCA). The energy disperse spectroscopy (EDS) mapping showed gradually reduced calcium distribution in the treated endoplasmic reticulum. Furthermore, HiOx-MAP treatment increased the caspase-3 activity and the apoptosis rate. The activity of calmodulin protein (CaMKKβ) and AMP-activated protein kinase (AMPK) was down-regulated leading to apoptosis. These results indicated that HiOx-MAP promoted apoptosis during postmortem aging to improve the tenderization of meat.

Exploring the spatial distribution pattern of rural relative poverty and its influencing factors is of great significance for solving the problem of poverty. This research calculates the relative poverty level of rural areas in China by using POVCAL software of the World Bank according to income grouping data and analyzes the spatial and temporal pattern characteristics. After establishing a spatial Durbin model to explore the influencing factors of rural relative poverty in China, the results are as follows. The level of relative poverty in rural China is on the rise as a whole, and there is a certain spatial dependence characteristic. Education differentiation and income gap between urban and rural areas have an aggravating effect on rural relative poverty, while rural medical level, rural social security level, and urban-rural segmentation can alleviate rural relative poverty.

The increasing inshore marine litters (IML) have been jeopardizing the coastal ecology and environment and have attracted widespread concerns. Nevertheless, the accurate detection and quantitative characterization of IML remain a challenge. In this study, a new method is proposed to automatically detect and extract the IML from terrestrial laser scanning (TLS) 3D point clouds. IML are progressively extracted from the surroundings through four major steps by jointly using the radiometric/intensity information and a series of derived geometric features. First, the intensity data are calibrated by a polynomial model for an initial segmentation according to the spectral differences between the IML and surroundings. Second, a new proposed model is used to calibrate the density data for a further discrimination based on the size discrepancies between the IML and surroundings. Third, a connectivity clustering algorithm is used to group the points into different clusters. Cluster geometric features in terms of the shapes and patterns (i.e., linearity, sizes, and verticality) are constructed to identify the IML. Fourth, a geometric self-repairing procedure is used to retrieve the misclassified IML points. An artificially-arranged scene on a bare mudflat and four natural scenes with different circumstances and IML categories are investigated to validate the proposed method. The overall accuracy and kappa coefficient of the proposed method are averagely 98% and 0.69, respectively. Compared with the classical methods, the proposed method shows good robustness performance in different natural scenes with varied IML categories, vegetation coverages, and environmental disturbances. The proposed method shows great promise in IML spatiotemporal interpretation and provides an alternative tool for the validation of large-scale IML products from space-borne or airborne remote sensing platforms.

As glaciers across the world continue to recede, there is a concern that their loss as a fresh water reservoir within mountainous basins will have a negative impact on stream temperatures and downstream water resources. Currently, there are relatively few glacio-hydrological models (GHMs) appropriate to study such phenomena and studies that have used GHMs generally acknowledge the high uncertainty associated with their simulations. Calibration techniques present a particular issue in GHMs as available glacier observations are limited and errors in the glacierized portion of a basin can be compensated by errors in the non-glacierized portion. Using as a study site the Cheakamus Basin in British Columbia, Canada, we 1) present a new, fully-coupled GHM, 2) analyze the effects different calibration techniques have on the model’s summer streamflow projections, and 3) compare the fully-coupled GHM results to projections using a one-way GHM. The calibration techniques studied vary in terms of glacier representation (dynamic/static), and glacier constraint (mass balance/thinning rates/thinning rates and area change). We find projected future climate forcings are sufficiently strong in the Cheakamus Basin so as to generally make the sign and significance of changes to the basin’s hydrology insensitive to the calibration and projection procedures studied. However, the variation among these procedures produces significant changes in the projected magnitude of future hydrological changes and therefore should be carefully considered in studies where precision beyond the sign and significance of change is required. Based on analysis of the variation within each procedure’s set of model outputs, we conclude 1) the two-way GHM has benefits over the one-way model, 2) calibration using dynamic glaciers and a thinning rate constraint is preferable for the new GHM, and 3) there is a need for additional studies on the uncertainties associated with the calibration of glacio-hydrological models.