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In this study, the tensile behaviors of laser powder bed fused (L-PBF) and laser powder directed energy deposited (LP-DED) HAYNES® 214 were investigated at a wide range of test temperatures (−195, 25, 425, 650, 870 and 980 °C). Specimens fabricated in the vertical orientation were subjected to a three-step heat treatment including stress relief, hot isostatic pressing, and solution treatment. The non-heat treated microstructures of L-PBF and LP-DED specimens were dendritic and columnar, oriented in the build direction. Recrystallization occurred after solution annealing, with the nucleation and growth of equiaxed grains. Tensile results revealed higher strength for the L-PBF specimens compared to LP-DED up to 650 °C, attributed to their finer grain size. The highest strengths were recorded at cryogenic temperatures, where diminished dislocation mobility and deformation twinning provided increased resistance to plastic deformation. From room temperature to 425 °C, a gradual decrease in strength was ascribed to the increase in dislocation motion with temperature. Ductility was measured to be similar for both processes up to 650 °C, and fracture surface analysis showed transgranular failure at these temperatures. A ductility dip was observed between temperatures of 650–870 °C due to the activation of grain boundary sliding resulting in intergranular cracking. The heterogeneous grain size distribution in both L-PBF and LP-DED specimens led to the ductility being comparable for both processes. The highest test temperature of 980 °C introduced sufficient thermal energy to promote significant grain boundary sliding which resulted in intergranular fracture in the L-PBF and LP-DED specimens.

With the recent implementation of additively manufactured parts into industrial applications, there is a dire need for nondestructive evaluation methods to qualify if these components are fit for service due to their sensitivity to processing conditions. The Impulse Excitation Technique (IET) is applied to additively manufactured Ti-6Al-4V bending specimens to determine natural frequencies and damping properties in order to predict fatigue performance relative to specimens fabricated with different processing parameters. From the damping and natural frequency results, it was found that the specimens, fabricated with intentional underheating to induce lack of fusion defects, had the lowest damping value in the pristine condition and the highest natural frequency. For the three batches of specimens tested, it was determined that the underheated specimens had the best fully-reversed bending fatigue performance with the highest fatigue limit (297 MPa) and longest fatigue lives as compared to the other two batches, implying a relation of decreased fatigue life with increased material damping in the pristine condition. The theory of the IET related to materials is presented with damping and fatigue results, as well as microstructural analysis and fractography of three specimens batches fabricated with different processing parameters.

Deteriorated filter condition in laser powder bed fusion (L-PBF) systems may negatively impact shield gas flow, causing inadequate spatter particle/plume removal, leading to laser beam attenuation and reduction in melt pool depth, and potentially causing more frequent formation of volumetric defects. This work investigated the effects of filter condition and part location on the micro-/defect-structure and mechanical behavior, including tensile and fatigue, of Ti-6Al-4V parts fabricated by L-PBF. Interestingly, within the manufacturer recommended service intervals, no specific effect of filter condition could be observed on the micro-/defect-structure or the mechanical behavior of the fabricated parts. However, the parts’ defect-structures were affected by their location, with ones located near the center of the build plate having less porosity than the ones located away. Although these defects did not affect the tensile properties, they frequently observed to initiate fatigue cracks (the critical defects sizes were often in the range of a few tens of micrometers). Therefore, their sensitivity to location resulted in the location dependence of the fatigue behavior.

Leaf anatomical traits are susceptible to environmental changes and can reflect plant adaptation strategies to the environment. Populus euphratica plays a key role in maintaining ecosystem processes and functions in arid zones, but the variations in leaf anatomical traits of Populus euphratica and their drivers at large scales remain unclear. Here, we investigated 10 leaf anatomical traits of Populus euphratica from 12 sampling sites in the arid zone of China, and explored how they were affected by geographic, climatic, and soil factors. Our results showed that these traits differed significantly between sites (P < 0.05), which was mainly determined by climate and soil factors that together explained 41.4 % of the trait variation. The impact of climate factors is the most critical, as they can directly influence the variation in leaf anatomical traits and indirectly affect trait variation by influencing soil factors. Among them, the max temperature of the warmest month (BIO5), soil available phosphorus (SAP) and soil moisture content (SM) had the most critical effect. Besides, temperature was the major influencing factor for the ratio of spongy tissue thickness to leaf thickness (SR), palisade tissue thickness (PT), the ratio of palisade tissue thickness to spongy tissue thickness (PSR), and the ratio of palisade tissue thickness to leaf thickness (CTR), while soil nutrient was the major influencing factor for leaf thickness (LT), lower epidermis thickness (LET), and spongy tissue thickness (ST). Our results provide important insights into the response of dryland forests to climate change, and suggest that climate warming and declining soil quality may have a stronger effect on Populus euphratica.

During freeze–thaw cycling, aggregates undergo a dynamic change in breakdown–formation (turnover), however, how the turnover occurs between aggregates of various particle sizes is not clear. To clarify the influence of freeze–thaw cycling on the dynamic changes in the particle size of soil aggregates, soil aggregates from the Black Soil Region of Northeast China were selected as the research objects. The study conducted in situ dynamic monitoring experiments, innovatively applying the rare earth oxide (REO) tracer method to natural conditions of freeze–thaw cycles (autumn freeze–thaw period, freezing period, and spring freeze–thaw period), accurately tracking the turnover paths and quantifying the turnover rates between aggregates of various particle sizes. The results revealed that the total value of the formation paths of the 2–5 mm aggregates and 0.25–2 mm aggregates increased during the autumn freeze–thaw period. The number of freeze–thaw cycles and accumulated snowfall were significantly positively correlated with aggregate stability, with an increase in the number of freeze–thaw cycles and accumulated snowfall resulting in an increase in the proportion of aggregates > 0.25 mm, which improved aggregate stability. In addition, the total value of the breakdown path of macro-aggregates increased during the spring freeze–thaw cycling period. Soil moisture was significantly negatively correlated with aggregate stability, with increased soil moisture resulting in a decrease in the percentage of aggregates > 0.25 mm, which resulted in a decrease in aggregate stability. The study can provide a reference understanding for the effects of freeze–thaw cycles on the structure of black soil and provide a theoretical basis for improving the quality of arable land.

Lunar lava tube caves, due to their unique geographical structure and potential as shelters, have repeatedly emerged as prime candidates or priority areas during discussions on lunar base site selection. However, owing to current technological limitations and the complexities of lunar exploration, obtaining detailed data directly from the interiors of lunar lava tubes poses a significant challenge. Hence, the study of terrestrial lava tubes assumes critical importance. By delving into Earth’s lava tubes, we can gain insights into crucial aspects such as their formation mechanisms, geological characteristics, and stability, which can then inform and guide research on lava tubes found on extraterrestrial bodies like the Moon and Mars. During the data acquisition process for lava tubes, given their intricate spatial configurations and dim lighting conditions, we have opted to employ LiDAR technology to collect point cloud data, revealing the internal structural information of the lava tubes. Consequently, this paper thoroughly explores a method for extracting lava tube parameters and constructing models using this point cloud data. This approach encompasses four key steps: data preprocessing, axis construction of the lava tube, cross-sectional feature extraction, and 3D model reconstruction. Initially, raw data is refined through the creation of point cloud voxels to mitigate noise interference. Subsequently, an iterative algorithm is utilized to obtain the L1-medial skeleton, enabling precise capture of the lava tube’s axis information. Using this extracted axis, we proceed with sampling at fixed intervals to derive cross-sectional points of the lava tube. These points are then utilized to extract fundamental geometric parameters such as cross-sectional area, length, and width. Ultimately, by integrating all these cross-sectional point cloud data, a comprehensive 3D model of the lava tube is constructed. Remarkably, this method achieves a high degree of accuracy, with 99 % of the extracted cross-sectional points exhibiting an error of less than 0.12 m, and 99 % of the model’s positional errors falling within 0.15 m. This not only enhances the precision of parameter extraction but also provides significant technical support for in-depth studies of extraterrestrial volcanic activities and lava tube formation mechanisms. Furthermore, it offers a valuable tool for parameter extraction and research on other irregular natural tunnels.

The tensile and fatigue properties of a newly developed Ni-based superalloy, HAYNES® 233, were investigated. Two different manufacturing processes including hot rolling (wrought plate) and laser-powder directed energy deposition (LP-DED) were considered. In addition, specimens were tested in two heat treatment (HT) conditions, namely solution annealed (SA), and age-hardened (AH). The microstructures of the materials were characterized using a scanning electron microscope. Tensile properties of specimens were evaluated at 21 °C, 538 °C, and 871 °C along with the fatigue properties at 21 °C under two different strain amplitudes of εa = 0.005 mm/mm and εa = 0.002 mm/mm. The LP-DED material in both the SA and AH conditions showed similar tensile strengths to the wrought AH material at all test temperatures, whereas the wrought SA material showed a noticeable deficit in strength at 21 °C and 538 °C, and was only comparable at 871 °C. Fatigue results indicated that there was no significant difference in fatigue life for specimens tested at εa = 0.005 mm/mm, while differences in fatigue life were observed for specimens tested at εa = 0.002 mm/mm, where fatigue life was observed to correlate well with the size of the crystallographic facets at crack initiation sites.

Monocytes are key effectors in autoimmunity-related diseases in the central nervous system (CNS) due to the critical roles of these cells in the production of proinflammatory cytokines, differentiation of T-helper (Th) cells, and antigen presentation. The JAK–STAT signaling is crucial for initiating monocytes induced immune responses by relaying cytokines signaling. However, the role of this pathway in modulating the communication between monocytes and Th cells in the pathogenesis of multiple sclerosis (MS) is unclear. Here, we show that the JAK1/2/3 and STAT1/3/5/6 subtypes involved in the demyelination mediated by the differentiation of pathological Th1 and Th17 and the CNS-infiltrating inflammatory monocytes in experimental autoimmune encephalomyelitis (EAE), a model for MS. JAK inhibition prevented the CNS-infiltrating CCR2-dependent Ly6Chi monocytes and monocyte-derived dendritic cells in EAE mice. In parallel, the proportion of GM-CSF+CD4+ T cells and GM-CSF secretion were decreased in pathological Th17 cells by JAK inhibition, which in turns converted CNS-invading monocytes into antigen-presenting cells to mediate tissue damage. Together, our data highlight the therapeutic potential of JAK inhibition in treating EAE by blocking the GM-CSF-driven inflammatory signature of monocytes.

The reliability of additively manufactured flexible electronics or so-called printed electronics is defined as mean time to failure under service conditions, which often involve mechanical loads. It is thus important to understand the mechanical behavior of the printed materials under such conditions to ensure their applicational reliability in, for example, sensors, biomedical devices, battery and storage, and flexible hybrid electronics. In this article, a testing protocol to examine the print quality of additively nanomanufactured electronics is presented. The print quality is assessed by both tensile and electrical resistivity responses during in-situ tension tests. A laser based additive nanomanufacturing method is used to print conductive silver lines on polyimide substrates, which is then tested in-situ under tension inside a scanning electron microscope (SEM). The surface morphology of the printed lines is continuously monitored via the SEM until failure. In addition, the real-time electrical resistance variations of the printed silver lines are measured in-situ with a multimeter during tensile tests conducted outside of the SEM. The protocol is shown to be effective in assessing print quality and aiding process tuning. Finally, it is revealed that samples appearing identical under the SEM can have significant different tendencies to delaminate.

In the current study, the effects of different post-processing methods, including heat treatment (HT) and electro-chemical polishing (ECP) as well as their combination on the surface texture, porosity, microstructure, mechanical properties, and rotating bending fatigue behavior of U-notched laser powder bed fused AlSi10Mg specimens were comprehensively investigated. In addition, to better understand the effects of the applied post-processing methods on the sensitivity of the notched specimen to surface and near-surface defects, finite element analysis was performed. Chemical treatment was found to be very influential on surface texture modification of the very narrow notched parts, for which the application of other treatments can be quite challenging. It was also found that the fatigue behavior of the notched specimens was more sensitive to the surface texture rather than to the near-surface defects. The hybrid treatment involving HT+ECP was the most effective for fatigue behavior improvement due to simultaneous homogenization of the microstructure, released tensile residual stresses, enhanced ductility and high surface texture modification.

In order to protect natural ecosystems, areas that can provide higher ecosystem services are usually designated as ecological priority protection areas. However, some areas with good natural and socio-cultural conditions (called ecological improvement zones in this study, EIZs) that do not provide the highest ecosystem services are often ignored. Therefore, this study attempts to use ecological functional zones as the research unit. And delineating the EIZs by combining multiple critical impact thresholds of ecosystem health (EH) change. Northwestern Hubei Province (NWHB), an important ecological function area in China, was selected as the study area. The results show that (1) the landscape of cultivated land tends to be fragmented, due to being occupied by a large amount of rural–urban land; (2) from 2000 to 2020, the EH in NWHB gradually improved; (3) spatially, the western region of NWHB is dominated by multiple ESs synergetic zone, while the eastern region is a food provision zone; and (4) except for GDP and population density, which are monotonically negatively correlated with EH, all other natural and anthropogenic factors have critical impact thresholds. The critical impact thresholds vary significantly among different ecological functional zones in different periods (e.g., In biodiversity - carbon storage synergetic zone, the threshold of DEM of around less than 1150 m in 2000 decreased to 480 m in 2005 with a clear trend of EH improvement). Meanwhile, from 2000 to 2020, EIZs are mainly distributed in key synergistic bundles in different periods. This study aims to provide services for the planning and management of ecological functional zones.

The resonant converter with modular rectifier (RMR) is a promising topology for DC grid applications. This paper studies the control strategy of RMR based SiC switching device including the output voltage and submodule (SM) capacitor voltage balancing control strategy. Firstly, different working modes of the RMR converter are analyzed, and the Critical Mode with the highest efficiency is introduced. A control method is proposed to guarantee the RMR operating the Critical Mode. The control parameters design is detailed. Secondly, the charging and discharging principles of SM capacitor voltages are introduced, then a balancing method is proposed: the SM capacitor voltages are sorted, then assign gate signals with smaller pulse width to SMs with lower capacitor voltages, and vice versa. The proposed control methods are verified by experimental results on a 300 V/1200 V 8 kW RMR prototype based SiC switching device. According to the experimental results, the RMR operates at the Critical Mode under different load and gain conditions. The SM capacitor voltages are well balanced. The peak efficiency is 98.2%.

This study investigated the microstructure and tensile properties of the NASA HR-1 (Fe-Ni-Cr) alloy using the laser powder directed energy deposition (LP-DED) process. Laser power and spot size were varied for deposition, and it was noted that low laser power could result in higher cooling rates and finer microstructure. The melt pool depth and width and the defect content increased with the increase in laser power. Out of several laser power (i.e., 350, 750, 1070, 2000, and 2620 W), the samples deposited using 750 W demonstrated the highest material density. In addition, the effects of heat treatment on the microstructure and tensile properties were investigated. It was found that a heat treatment schedule consisting of stress relief, homogenization, solution treatment, and aging could thoroughly homogenize the microstructure (i.e., remove the as-solidified dendritic microstructure), result in relatively uniform, equiaxed grains, and increase the material hardness. Importantly, this heat treatment schedule efficiently reduced titanium segregation, preventing the formation of deleterious needle-shaped η (Ni3Ti) precipitates in NASA HR-1, known to be detrimental to mechanical properties and resulted in almost comparable tensile properties with varying laser power.

Summary: Combinatorial CRISPR screening is useful for investigating synthetic lethality (SL) gene pairs. Here, we detail the steps for dual-gRNA library construction, with the introduction of two backbones, LentiGuide_DKO and LentiCRISPR_DKO. We describe steps for in vitro screening with 22Rv1-Cas9 and SaOS2-Cas9 cells followed by sequencing and data analysis. By introducing two backbones, we optimized the library construction process, facilitated standard pair-end sequencing, and provided options of screening on cells with or without modification of Cas9 expression. : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Summary: This paper develops a multi-sector and multi-factor structural gravity model that allows an analytical and quantitative decomposition of the emission and output changes into composition and technique effects. We find that the negative production shock of China’s containment policy propagates globally via supply chains, with the carbon-intensive sectors experiencing the greatest carbon emission shocks. We further reveal that China’s current stimulus package in 2021–2025 is consistent with China’s emission intensity-reduction goals for 2025, but further efforts are required to meet China’s carbon emissions-peaking target in 2030 and Cancun 2°C goal. Short-term changes in carbon emissions resulting from lockdowns and initial fiscal stimuli in “economic rescue” period have minor long-term effects, whereas the transitional direction of future fiscal stimulus exerts more predominant impact on long-term carbon emissions. The efficiency improvement effects are more important than the sectoral structure effects of the fiscal stimulus in achieving greener economic growth.

Objectives: The aim of this study was to determine whether convalescent blood products (CBPs) offer a survival advantage for patients with severe acute respiratory infections of viral etiology. Methods: Up-to-date trials were identified by the authors through searches of the MEDLINE, Embase, Cochrane Library, Web of Science, ClinicalTrials.gov, and medRxiv databases from inception up to September 14, 2020. Meta-analyses were performed using a random-effects model. Results: According to the observational studies, patients who received CBPs showed a decline in all-cause mortality compared with patients who did not receive CBPs (odds ratio (OR) 0.36, 95% confidence interval (CI) 0.23–0.56; p < 0.00001). However, the randomized controlled trials (RCTs) showed no difference between the intervention group and the control group regarding all-cause mortality (OR 0.82, 95% CI 0.57–1.19; p = 0.30). The use of CBPs did not increase the risk of adverse events (OR 0.88, 95% CI 0.60–1.29; p = 0.51). Using CBPs earlier compared with using CBPs later was associated with a significant reduction in all-cause mortality (OR 0.18, 95% CI 0.08–0.40; p < 0.0001). Conclusions: Based on the outcomes of RCTs, CBPs may not decrease all-cause mortality. Furthermore, compared with later initiation of CBP therapy, earlier initiation of this therapy may decrease the rate of mortality.

G Protein-Coupled Receptors (GPCRs) are one of the largest membrane protein receptor family in human, which are also important targets for many drugs. Thence, it’s of great significance to judge whether a protein is a GPCR or not. However, identifying GPCRs by experimental methods is very expensive and time-consuming. As more and more GPCR primary sequences are accumulated, it’s feasible to develop a computational model to predict GPCRs precisely and quickly. In this paper, a novel method called EMCBOW-GPCR has been proposed to improve the accuracy of identifying GPCRs based on natural language processing (NLP). For representing GPCRs, three word-embedding models and a bag-of-words model are used to extract original features. Then, the original features are thrown into a Deep-learning algorithm to extract features further and reduce the dimension. Finally, the obtained features are fed into Extreme Gradient Boosting. As shown with the results comparison, the overall prediction metrics of EMCBOW-GPCR are higher than the state of the arts. In order to be convenient for more researchers to use EMCBOW-GPCR, the method and source code have been opened in github, which are available at https://github.com/454170054/EMCBOW-GPCR, and a user-friendly web-server for EMCBOW-GPCR has been established at http://www.jci-bioinfo.cn/emcbowgpcr.

Three new C20-diterpenoid alkaloids with a sulfonic acid unit, named aconicarmisulfonines B and C (1 and 2) and chuanfusulfonine A (3), respectively, were isolated from the Aconitum carmichaelii lateral roots (“fu zi” in Chinese). Structures of 1–3 were determined by spectroscopic data analysis. Intriguing chemical properties and reactions were observed for the C20-diterpenoid alkaloids: (a) specific selective nucleophilic addition of the carbonyl (C-12) in 1 with CD3OD; (b) interconversion between 1 and 2 in D2O; (c) stereo- and/or regioselective deuterations of H-11α in 1–3 and both H-11α and H-11β in aconicarmisulfonine A (4); (d) TMSP-2,2,3,3-d4 promoted cleavage of the C-12−C-13 bond of 4 in D2O; (e) dehydrogenation of 4 in pyridine-d5, and (f) Na2SO3-assisted dehydrogenation and N-deethylation of songorine (5, a putative precursor of 1–4). Biogenetically, 1 and 2 are correlated with 4, for which the same novel carbon skeleton is proposed to be derived from semipinacol rearrangements via migrations of C-13−C-16 and C-15−C-16 bonds of the napelline-type skeleton, respectively. Meanwhile, 3 is a highly possible precursor or a concurrent product in the biosynthetic pathways of 1, 2, and 4. In the acetic acid-induced mice writhing assay, at 1.0 mg/kg (i.p.), compounds 1, 2, 5, 5a, and 5b exhibited analgesic effects against mice writhing.

Edwardsiella piscicida is one of the important pathogens in aquaculture, which takes huge losses to the economic benefits of turbot industry. Thus, a simple, rapid and accurate diagnostic assay of E. piscicida becomes an urgent need. In the present study, a detection method of E. piscicida based on recombinase polymerase amplification combined with lateral flow strip (RPA-LF) was established. The RPA-LF assay targeted E. piscicida evpP gene and could detect as low as 10 fg DNA of E. piscicida, which was approximately 1000 times more sensitive than conventional PCR assay. Meanwhile, the RPA-LF assay showed no cross-reactivity with DNA from other major bacterial pathogens in aquaculture. Besides, to improve the convenience of RPA-LF assay, a rapid on-the-spot sample preparation using nucleic acid extraction by cellulose dipsticks was established. Results indicated that bacteria could be detected as low as 1 copy and completed within 30 min. Moreover, this modified RPA-LF assay could be used to monitor E. piscicida infection in turbot industry.

Summary: Background: Screening for atrial fibrillation before onset of symptoms and the subsequent initiation of oral anticoagulants could prevent stroke and death. The most cost-effective strategy to screen for atrial fibrillation in a population at high risk aged 65 years and older is unknown. Therefore, we aimed to investigate whether more frequent electrocardiography (ECG) recordings would significantly improve the detection of atrial fibrillation compared with annual ECG screenings. Methods: We did a randomised controlled trial that compared different screening frequencies of 30 s single-lead ECG (AliveCor Heart Monitor) in the detection of atrial fibrillation in Chinese residents (≥65 years) in five community health centres in Shanghai, China. Only participants without history of atrial fibrillation and without atrial fibrillation rhythm at baseline were eligible for inclusion in the trial. Random assignment was done with the use of a random number table and stratified for study site. Participants were randomly assigned in a 1:1 ratio to annual or quarterly screening groups. The quarterly screening group was further randomly assigned in a 3:1 ratio to subgroups of quarterly screening and quarterly screening plus (which involved ECG screening once per week for the first month of follow-up, then quarterly for the remainder of follow-up). The primary outcome was the detection rate of atrial fibrillation. The intention-to-treat analysis was done for all randomly assigned patients who had at least one ECG recording during follow-up. This trial was registered at ClinicalTrials.gov, NCT02990741, and terminated on Oct 31, 2020. Findings: Between April 17, 2017, and June 26, 2018, 8240 participants were randomly assigned to annual screening (n=4120), quarterly screening (n=3090), and quarterly screening plus (n=1030), with a mean number of ECG recordings of 1·6 (SD 0·5) for annual screening, 3·5 (1·5) for quarterly screening, and 5·2 (2·9) for quarterly screening plus during a median of 2·1 years follow-up (13 284 person-years). 73 incident cases of atrial fibrillation occurred: 26 in the annual screening group (4·1 per 1000 person-years) and 47 in the quarterly screening group (6·7 per 1000 person-years. Quarterly screening was associated with a significant increase in the detection rate of atrial fibrillation, compared with annual screening (hazard ratio [HR] 1·71; 95% CI 1·06–2·76; p=0·029). 40 incident cases were detected in quarterly screening (7·2 per 1000 person-years; HR compared to annual screening, 1·83; 95% CI 1·12–3·00; p=0·017) and seven in the quarterly screening plus group (4·8 per 1000 person-years; HR compared with annual screening, 1·24; 0·54–2·86; p=0·61). No significant difference was noted between quarterly screening and the quarterly screening plus group (HR of quarterly screening plus compared with quarterly screening, 0·68; 0·30–1·52; p=0·35). Interpretation: Quarterly 30 s single-lead ECG screening was associated with a significantly higher detection rate of incident atrial fibrillation compared with annual screening, but additional once per week screenings in the first month did not yield an added predictive value. Quarterly screening might be considered in a general population at a high risk of atrial fibrillation, such as those aged 65 years and older. Funding: Bayer Healthcare Company.

Bisphenol analogues including bisphenol A (BPA), bisphenol AF (BPAF), bisphenol F (BPF), and bisphenol S (BPS) share similar chemical structures and endocrine disrupting effects. Their effects on metabolisms, however, are so far only marginally understood. In this study, NMR-based metabonomic profiles of HepG2 cell culture media and PCR array were used to assess the metabolomics disturbances and gene expression levels of HepG2 in response to four BPs (BPA, BPAF, BPF, and BPS). The results indicated that BP analogues resulted in disturbances in 7–15 metabolites that were classified as amino acid (alanine, glutamine, glutamate), intermediates and end-products in the glycolysis (pyruvate) and the tricarboxylic acid cycle (acetate, lactate). Their rank in order according to the number of metabolites and pathways was BPF > BPA > BPAF > BPS. The common disrupted pathways (pyruvate metabolism; alanine, aspartate, and glutamate metabolism) indicated enhanced glycolysis. The following glucometabolic PCR array analysis suggested that although four BPs shared the capability of disrupting glucose metabolism, they may act through different mechanisms: BPAF has increased the pyruvate kinase (PKLR) expression level, which implied enhanced glycolysis that was agreed with NMR results. The other three BP analogues, however, decreased the expression level of glucokinase (GCK) that indicated glucose sensing impairment. Our results demonstrated the potential for using metabolomic and PCR array to understand the underlying action of mechanisms and identify the potential targets for future targeted risk assessment. Keywords: Bisphenol analogues, Metabolomic modulations, HepG2, PCR array

Summary: Resin embedding is widely used to dissect the fine structure of bio-tissue with electron and optical microscopy. However, it is difficult to embed large-volume tissues with resin. Here, we modified the formula of LR-White resin to prevent the sample cracking during polymerization process and applied this method to the intact brains of mouse, ferret, and macaque. Meanwhile, we increased the fluorescence preservation rate for green fluorescent protein (GFP) from 73 ± 4.0% to 126 ± 3.0% and tdTomato from 60 ± 3.3% to 117 ± 2.8%. Combined with the whole-brain imaging system, we acquired the cytoarchitectonic information and the circuit information such as individual axon and boutons which were labeled with multiple fluorescent proteins. This method shows great potential in the study of continuous fine microstructure information in large-volume tissues from different species, which can facilitate the neuroscience research and help the understanding of the structure-function relationship in complex bio-tissues.

Summary: Cell membrane is the first medium from where a cell senses and responds to external stress stimuli. Exploring the tension changes in cell membrane will help us to understand intracellular force transmission. Here, a biosensor (named MSS) based on fluorescence resonance energy transfer is developed to visualize cell membrane tension. Validity of the biosensor is first verified for the detection of cell membrane tension. Results show a shear stress-induced heterogeneous distribution of membrane tension with the biosensor, which is strengthened by the disruption of microfilaments or enhancement of membrane fluidity, but weakened by the reduction of membrane fluidity or disruption of microtubules. These findings suggest that the MSS biosensor is a beneficial tool to visualize the changes and distribution of cell membrane tension. Besides, cell membrane tension does not display obvious polar distribution, indicating that cellular polarity changes do not first occur on the cell membrane during mechanical transmission. : Sensor; Molecular Biology; Membrane Architecture; Biophysics Subject Areas: Sensor, Molecular Biology, Membrane Architecture, Biophysics

The effect of the Rabdosia rubescens total flavonoids on focal cerebral ischemia reperfusion model in rats was observed. The model group, nimodipine group, cerebral collateral group, and large, medium and small dose group of the Rabdosia rubescens total flavonoids were administered with corresponding drugs but sham operation group and model group were administered the same volume of 0.5%CMC, 1 times a day, continuous administration of 7 d. After 1 h at 7 d to medicine, left incision in the middle of the neck of rats after anesthesia, we can firstly expose and isolate the left common carotid artery (CCA), and then expose external carotid artery (ECA) and internal carotid artery (ICA). The common carotid artery and the external carotid artery are ligated. Then internal carotid artery with arterial clamp is temporarily clipped. Besides, cut the incision of 0.2 mm from 5 cm of the bifurcation of the common carotid artery. A thread Line bolt is inserted with more than 18–20 mm from bifurcation of CCA into the internal carotid artery until there is resistance. Then the entrance of the middle cerebral artery is blocked and internal carotid artery is ligated (the blank group only exposed the left blood vessel without Plugging wire). Finally it is gently pulled out the plug line after 2 h. Results: Compared with the model mice, Rabdosia rubescens total flavonoids can significantly relieve the injury of brain in hippocampus and cortex nerve cells; experimental rat focal cerebral ischemia was to improve again perfusion model of nerve function defect score mortality; significantly reduce brain homogenate NOS activity and no content, MDA, IL-1, TNF-a, ICAM-1 content; increase in brain homogenate SOD and ATPase activity (P

Background: In a landscape of rising chronic disease burden in middle-income and high-income countries, digital health is seen as a promising solution to improving population health. Importantly, the development and uptake of digital health technologies require multisectoral efforts from academia and industry. However, few have explored the factors that help or hinder the success of these collaborations. Our study aims to identify the themes, barriers, and facilitators associated with industry–academia collaborations in digital health in middle-income and high-income countries. Methods: Trained researchers conducted semi-structured interviews with 23 stakeholders who are active in industry (n=11), academia (n=11), or both (n=1) using prespecified interview guides. Stakeholders were based in World-Bank-defined middle-income countries (China, India; n=15) or high-income countries (USA, Australia, Singapore; n=8). Interviews were conducted in the stakeholder's language of choice (Chinese, n=12; English, n=11). Qualitative interview questions elicited discussions about stakeholders' past experience with academia–industry collaboration, challenges they faced, and factors that facilitated the process. Interviews were audiotaped, transcribed verbatim, and analysed using inductive content analysis. A codebook was developed by the research team over five iterations and used by two bilingual coders to thematically code the data. Findings: Four central themes emerged from the discussions: stakeholder role in collaboration, communication between partners, goals or expectations, and individual priorities. Stakeholders in both academia and industry identified several facilitating factors for successful collaborations: the adoption of complementary roles; authentic communication between partners; and clearly outlined goals or expectations before the collaboration begins. Misaligned goals or expectations, particularly differences in timeline and difficulties balancing business outcomes versus scientific evidence, were identified as the primary barriers. Stakeholders in high-income countries reported inauthentic communication as a significant barrier to collaboration, whereas those in middle-income countries did not. Interpretation: This study highlights the need for increased planning and communication prior to and throughout collaborations between academia and industry in the field of digital health. Outlining each party's goals and expectations about timelines, assigning complementary roles, and communication about priorities will facilitate fruitful collaborations in the future. Furthermore, best practices for communication styles may depend on the cultural setting and, thus, should be adopted accordingly. Funding: None.