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Abstract Oxidative stress, caused by the accumulation of reactive oxygen species (ROS), is a pathological factor in several incurable neurodegenerative conditions as well as in stroke. However, our knowledge of the genetic elements that can be manipulated to protect neurons from oxidative stress-induced cell death is still very limited. Here, using Caenorhabditis elegans as a model system, combined with the optogenetic tool KillerRed to spatially and temporally control ROS generation, we identify a previously uncharacterized gene, oxidative stress protective 1 (osp-1), that protects C. elegans neurons from oxidative damage. Using rodent and human cell cultures, we also show that the protective effect of OSP-1 extends to mammalian cells. Moreover, we demonstrate that OSP-1 functions in a strictly cell-autonomous fashion, and that it localizes to the endoplasmic reticulum (ER) where it has an ER-remodeling function. Finally, we present evidence suggesting that OSP-1 may exert its neuroprotective function by influencing autophagy. Our results point to a potential role of OSP-1 in modulating autophagy, and suggest that overactivation of this cellular process could contribute to neuronal death triggered by oxidative damage.

Abstract Brain organoids provide a unique opportunity to model organ development in a system similar to human organogenesis in vivo. Brain organoids thus hold great promise for drug screening and disease modeling. Conventional approaches to organoid characterization predominantly rely on molecular analysis methods, which are expensive, time-consuming, labor-intensive, and involve the destruction of the valuable three-dimensional (3D) architecture of the organoids. This reliance on end-point assays makes it challenging to assess cellular and subcellular events occurring during organoid development in their 3D context. As a result, the long developmental processes are not monitored nor assessed. The ability to perform non-invasive assays is critical for longitudinally assessing features of organoid development during culture. In this paper, we demonstrate a label-free high-content imaging approach for observing changes in organoid morphology and structural changes occurring at the cellular and subcellular level. Enabled by microfluidic-based culture of 3D cell systems and a novel 3D quantitative phase imaging method, we demonstrate the ability to perform non-destructive high-resolution quantitative image analysis of the organoid. The highlighted results demonstrated in this paper provide a new approach to performing live, non-destructive monitoring of organoid systems during culture.

IGFBP6, a member of the IGF binding protein (IGFBP) family, is a specific inhibitor of insulin-like growth factor II (IGF-II) and can inhibit the growth of malignant tumors overexpressing IGF-II. Type 2 diabetes (T2D) is a basic disorder of glucose metabolism that can be regulated by IGF-related pathways. We performed bioinformatics analysis of the TCGA database to explore the possible mechanism of IGFBP6 in breast cancer (BC) metabolism and prognosis and collected clinical samples from BC patients with and without T2D to compare and verify the prognostic effect of IGFBP6. In our study, the levels of IGFBP1–6 were positively correlated with overall survival (OS) in patients with breast cancer. IGFBP6 was upregulated in estrogen receptor (ER)-positive BC, and ER-positive and progesterone receptor (PR) positive patients had a higher expression level of IGFBP6 than ER-negative and PR-negative patients. IGFBP6 could be used as an independent prognostic factor in BC. The expression of IGFBP6 was decreased in BC tissue, and BC tissue from patients with T2D had lower IGFBP6 expression levels than BC tissue from patients without T2D. IGFBP6 is mainly involved in the PI3K–Akt and TGF-β signaling pathways and tumor microenvironment regulation. In terms of metabolism, the expression of IGFBP6 was negatively correlated with that of most glucose metabolism-related genes. IGFBP6 expression was mainly correlated with mutations in TP53, PIK3CA, CDH1, and MAP3K1. In addition, the upregulation of IGFBP6 in BC increased the drug sensitivity to docetaxel, paclitaxel and gemcitabine. Overall, these results indicated that high expression of IGFBP6 is associated with a good prognosis in BC patients, especially in those without T2D. It is not only involved in the maintenance of the tumor microenvironment in BC but also inhibits the energy metabolism of cancer cells through glucose metabolism-related pathways. These findings may provide a new perspective on IGFBP6 as a potential prognostic marker for BC.

Abstract Background Benign paroxysmal positional vertigo (BPPV) is a prevalent form of vertigo that necessitates a skilled physician to diagnose by observing the nystagmus and vertigo resulting from specific changes in the patient’s position. In this study, we aim to explore the integration of eye movement video and position information for BPPV diagnosis and apply artificial intelligence (AI) methods to improve the accuracy of BPPV diagnosis. Methods We collected eye movement video and diagnostic data from 518 patients with BPPV who visited the hospital for examination from January to March 2021 and developed a BPPV dataset. Based on the characteristics of the dataset, we propose a multimodal deep learning diagnostic model, which combines a video understanding model, self-encoder, and cross-attention mechanism structure. Result Our validation test on the test set showed that the average accuracy of the model reached 81.7%, demonstrating the effectiveness of the proposed multimodal deep learning method for BPPV diagnosis. Furthermore, our study highlights the significance of combining head position information and eye movement information in BPPV diagnosis. We also found that postural and eye movement information plays a critical role in the diagnosis of BPPV, as demonstrated by exploring the necessity of postural information for the diagnostic model and the contribution of cross-attention mechanisms to the fusion of postural and oculomotor information. Our results underscore the potential of AI-based methods for improving the accuracy of BPPV diagnosis and the importance of considering both postural and oculomotor information in BPPV diagnosis.

In this paper, the damage constitutive model of reactive powder concrete (RPC) in uniaxial tension is investigated. The relationship between the uniaxial tensile strength of RPC and the steel fiber admixture was analyzed by preparing RPC specimens with different steel fiber volume admixtures for uniaxial tensile tests, and the stress–strain curves were recorded. The test results show that the uniaxial tensile strength of RPC is significantly enhanced with an increase in steel fiber doping, especially after the doping amount is greater than 2%, showing a linear increase. Based on the classical damage mechanics and Weibull distribution, the damage evolution equation and the constitutive model of RPC uniaxial tension were established. The validation shows that the model can effectively describe the damage process of RPC in uniaxial tension, which provides a theoretical basis for the application of RPC in engineering practice.

The disclosure of recovery journeys on social media by individuals with substance use is a growing trend, but its impact on public attitudes toward stigmatized groups is not well-understood. To address this gap, an experiment was conducted with 1,438 U.S. adults who viewed a series of Instagram posts about a person’s recovery journey. Participants were randomly assigned to view posts that either included a relapse episode or not. Structural equation modeling was used for data analyses. The results revealed that presenting a relapse narrative increased feelings of compassion, anger, and pity. In addition, mediation analyses provided evidence supporting the role these emotions played in mediating the effects of a relapse narrative on stigma beliefs and desire for social distance. These findings prompt a reevaluation of digital storytelling practices in health communication strategies, aiming for a balanced representation that can effectively reduce stigma and promote community support for those navigating substance use recovery. It is recommended to incorporate the study’s insights into educational content, therapeutic interventions, and policy formulations to foster a more supportive and understanding environment for individuals in recovery.

With the rapid development of drilling automation, how to automate real-time online measure drilling fluid rheology accurately has become one of the problems that the industry urgently wants to solve. At present, the common method is the rheological measurement method of straight pipe drilling fluid, but often the pumping equipment will produce pulsating flow during reciprocating pumping, resulting in a large error in the data of pressure difference and flow measurement, and the corresponding rheological parameters obtained are not accurate. In order to solve the problem of low accuracy of rheological parameters, this paper proposes an online measurement method for the rheology of straight tubular oil-based drilling fluids under pulsating flow, and firstly establishes an online measurement model of the rheology of straight tubular oil-based drilling fluids. Then, fluent is used to simulate and analyze the fluid movement of drilling fluid with different rheology in the measuring tube, and then analyze the error of differential pressure measurement and flow measurement of the measuring tube under the fluctuating flow. The actual measurement environment was simulated as the initialization parameters of the fluent simulation, and the calibration model of the oil-based drilling fluid measured by the device under the influence of pulsation was established. Finally, the experimental bench was built, and the experimental results showed that the calculated rheological parameters were 2.69% for apparent viscosity (AV), 2.362% for plastic viscosity (PV) and 3.056% for yield point (YP), which effectively improved the online measurement accuracy of straight tube oil-based drilling fluid.

Abstract Some double-circuit transmission lines are untransposed, which results in complex coupling relations between the parameters of the transmission lines. If the traditional modal transformation matrix is directly used to decouple the parameters, it can lead to large errors in the decoupled modal parameter, errors which will be amplified in the fault location equation. Consequently, it makes the fault location results of the untransposed double-circuit transmission lines less accurate. Therefore, a new modal transformation method is needed to decouple the parameter matrix of untransposed double-circuit transmission lines and realize the fault location according to the decoupled modal parameter. By improving the basis of the Karrenbauer matrix, a modal transformation matrix suitable for decoupling parameters of untransposed double-circuit transmission lines is obtained. To address the difficulties in solving the fault location equation of untransposed double-circuit transmission lines, a new fault location method based on an improved Karrenbauer matrix and the quantum-behaved particle swarm optimization (QPSO) algorithm is proposed. Firstly, the line parameter matrix is decomposed into identical and inverse sequence components using the identical-inverse sequence component transformation. The Karrenbauer matrix is then transformed to obtain the improved Karrenbauer matrix for untransposed double-circuit transmission lines and applied to identical and inverse sequence components to solve the decoupled modal parameter. Secondly, based on the principle that voltage magnitudes at both ends are equal, the fault location equation is expressed using sequence components at each end, and the QPSO algorithm is introduced to solve the equation. Finally, the feasibility and accuracy of the proposed method are verified by PSCAD simulation. The simulation results fully demonstrate that the innovative improvement on the basis of the traditional modal transformation matrix in this paper can realize the modal transformation of the complex coupling parameters of the untransposed double-circuit transmission lines. It causes almost no errors in the decoupling process. The QPSO algorithm can also solve the fault location equation more accurately. The new fault location method can realize the accurate fault location of untransposed double-circuit transmission lines.

Stringent response and quorum sensing (QS) are two essential mechanisms that control bacterial global metabolism for better survival. Sphingomonads are a clade of bacteria that survive successfully in diverse ecosystems. In silico survey indicated that 36 out of 79 investigated sphingomonads strains contained more than one luxI homolog, the gene responsible for the biosynthesis of QS signal acyl homoserine lactones (AHLs). Investigation of the regulatory effects of the stringent response gene rsh on QS related bioactivities were carried out using rsh mutants of Sphingobium japonicum UT26 and Sphingobium sp. SYK-6, both had three luxI homologs. Results indicated that deletion of rsh upregulated the overall production of AHLs and extracellular polymeric substances (EPS) in both UT26 and SYK-6 in rich medium, but affected expressions of these luxI/luxR homologs in different ways. In the poor medium (1% LB), rsh mutant of SYK-6 significantly lost AHLs production in broth cultivation but not in biofilm cultivation. The regulatory effects of rsh on QS activities were growth phase dependent in UT26 and culture condition dependent in SYK-6. Our results demonstrated the negative regulatory effect of rsh on QS activities in sphingomonads, which were very different from the positive effect found in sphingomonads containing only one luxI/R circuit. This study extends the current knowledge on the intricate networks between stringent response and QS system in sphingomonads, which would help to understand their survival advantage.

Joining single crystal superalloy with polycrystalline superalloy has important applications in the aerospace industry. Here, the IC10 single crystal superalloy to GH536 polycrystalline superalloy was diffusion brazed using a BNi-2 filler alloy. The effects of bonding temperature and time on the microstructure evolution and mechanical properties of the GH536/IC10 joints were investigated in detail. The results elucidated that the joint brazed at a lower temperature and time (i.e., 1050 °C/30min) was composed of diffusion affected zone (DAZ), athermal solidification zone (ASZ), and isothermal solidification zone (ISZ). The secondary precipitates formed in DAZ were Cr-rich borides, Cr–Mo borides, and Cr–Mo–W borides. The ASZ was made up of Cr-rich borides, Ni-rich borides, Ni–Cr borides, and Ni-based solid solutions. These borides with high hardness were the potential source of cracks and caused the joints to fracture under a lower load. Raising bonding temperature and time gradually eliminated Ni-rich borides in ASZ and Cr-rich borides in DAZ, and improved the shear strength.

This study investigates the skid resistance performance of asphalt mixtures containing composite aggregates of basalt and limestone. The research aimed to predict the service life of the asphalt mixtures and identify the optimal basalt content for enhanced performance. Using an accelerated friction tester, friction indices such as the British pendulum number (BPN), mean texture depth (MTD), and dynamic friction coefficient (Dµ) were measured. The study conducted accelerated wear tests on mixtures with varying basalt contents under different water flow rates and loads. Results indicate that anti-skid performance decreased with increasing water flow, load, and wear cycles, initially showing a sharp decline followed by a gradual stabilization. Orthogonal experiments determined that basalt content had the most significant impact on skid resistance, followed by load and water flow rate. By converting skid resistance and MTD values into IFI values, a four-area diagram was created to illustrate skid resistance deterioration. The four-area IFI diagram also demonstrated that higher basalt content significantly enhances the skid resistance and service life of asphalt mixtures. Cost analysis based on life prediction showed that a 40% basalt content mixture is cost effective while maintaining excellent skid resistance. A test section study further validated that a 40% basalt content ensures good skid resistance, with indoor test predictions aligning closely with field data. Although the test section has been operational for only two years, ongoing monitoring will provide further insights into long-term skid resistance performance.

Visualizing synaptic connectivity has traditionally relied on time-consuming electron microscopy-based imaging approaches. To scale the analysis of synaptic connectivity, fluorescent protein-based techniques have been established, ranging from the labeling of specific pre- or post-synaptic components of chemical or electrical synapses to transsynaptic proximity labeling technology such as GRASP and iBLINC. In this paper, we describe WormPsyQi, a generalizable image analysis pipeline that automatically quantifies synaptically localized fluorescent signals in a high-throughput and robust manner, with reduced human bias. We also present a resource of 30 transgenic strains that label chemical or electrical synapses throughout the nervous system of the nematode Caenorhabditis elegans, using CLA-1, RAB-3, GRASP (chemical synapses), or innexin (electrical synapse) reporters. We show that WormPsyQi captures synaptic structures in spite of substantial heterogeneity in neurite morphology, fluorescence signal, and imaging parameters. We use these toolkits to quantify multiple obvious and subtle features of synapses – such as number, size, intensity, and spatial distribution of synapses – in datasets spanning various regions of the nervous system, developmental stages, and sexes. Although the pipeline is described in the context of synapses, it may be utilized for other ‘punctate’ signals, such as fluorescently tagged neurotransmitter receptors and cell adhesion molecules, as well as proteins in other subcellular contexts. By overcoming constraints on time, sample size, cell morphology, and phenotypic space, this work represents a powerful resource for further analysis of synapse biology in C. elegans.

Abstract Compared with aqueous single‐ion batteries, rechargeable aqueous hybrid ion batteries, especially Li+/Zn2+hybrid ion batteries, are receiving extensive interest owing to their low cost, high operating voltage, and energy density. However, their working voltage and lifespan are limited by the decomposition of water and the growth of Zn dendrites. Herein, detrimental side reactions induced by the water reduction and the Zn dendrite growth are successfully suppressed by a poly(propylene glycol) (PPG)‐based hybrid ion electrolyte [(1 m Zn(TFSI)2 + 10 m LiTFSI) in PPG/H2O]. The addition of PPG in the electrolyte can not only enhance the bonding strength of hydrogen‐bond in water but also tailor the solvation sheath of Zn2+ as revealed by synchrotron X‐rays. The participated solvation of PPG with Zn2+ can weaken Zn−H2O interactions and redistribute Zn2+ flux on the surface of the Zn anode, thus inducing favorably even deposition of Zn. In addition, the decomposition of TFSI− contributes a ZnF2 ‐enriched solid electrolyte interface at the Zn anode to further prevent water decomposition and restrain Zn dendrites. The PPG‐based electrolyte enables 2.1 V LiMnO2//Zn batteries to deliver high specific capacities (121.7 mAh g−1 for a coin cell and 90 mAh g−1 for a pouch cell), and maintain 80% of the capacity over 700 cycles at 0.5 C, suggesting a promising pathway for highly reversible aqueous hybrid ion batteries.

According to Bronfenbrenner’s ecological theory, the interaction between micro- and macro-factors improves human development. Previous studies suggest that community social capital, which refers to the interaction between residents and communities, promotes the subjective well-being of residents in residential communities. However, little is known about the mechanisms underlying this relationship. This study explored the link between community social capital and life satisfaction among urban residents and examined the mediating role of psychological flourishing and moderating effect of educational level. Data were obtained from a cross-community survey of 816 urban residents in China aged 20–60 years. The results indicated that psychological flourishing mediated the link between community social capital and life satisfaction among urban residents after controlling for gender, age, marital status, dwelling time, and monthly income. Furthermore, educational attainment moderated the association between community social capital and psychological flourishing. The mediating effect of psychological flourishing was stronger among residents with low educational attainment than those with high educational attainment, indicating that the benefits of community social capital were greater among the former group. This study extends our knowledge of the effect of community social capital on urban residents’ subjective well-being, including its role in reducing educational inequality in human well-being.

Bemisia tabaci is distributed globally and incurs considerable economic and ecological costs as an agricultural pest and viral vector. The entomopathogenic fungus Metarhizium anisopliae has been known for its insecticidal activity, but its impacts on whiteflies are understudied. We investigated how infection with the semi-persistently transmitted Cucurbit chlorotic yellows virus (CCYV) affects whitefly susceptibility to M. anisopliae exposure. We discovered that viruliferous whiteflies exhibited increased mortality when fungus infection was present compared to non-viruliferous insects. High throughput 16S rRNA sequencing also revealed significant alterations of the whitefly bacterial microbiome diversity and structure due to both CCYV and fungal presence. Specifically, the obligate symbiont Portiera decreased in relative abundance in viruliferous whiteflies exposed to M. anisopliae. Facultative Hamiltonella and Rickettsia symbionts exhibited variability across groups but dominated in fungus-treated non-viruliferous whiteflies. Our results illuminate triangular interplay between pest insects, their pathogens, and symbionts—dynamics which can inform integrated management strategies leveraging biopesticides This work underscores the promise of M. anisopliae for sustainable whitefly control while laying the groundwork for elucidating mechanisms behind microbe-mediated shifts in vector competence.

Abstract Background Colorectal cancer is one of the most common cancers in the world. Several studies suggest using the Asia-Pacific colorectal screening (APCS) score and its modified versions to select high-risk populations for early colonoscopy, but external validation remains rare, and which score should be selected for CRC screening in China is unclear. Validation of multiple scores in the same population might help to choose the best performing score. Methods We conducted a cross-sectional study under the framework of Cancer Screening Program in Urban China, data from asymptomatic colorectal cancer screening in Xuzhou was used to validate the APCS score, the colorectal neoplasia predict (CNP) score, the Korean colorectal screening (KCS) score, the Modified APCS score and the 8-point risk score in predicting colorectal advanced neoplasia (CAN). Results 1804 subjects were included in the analysis and 112 CAN (6.21%) was detected. In each score, the detection rate of CAN was higher in the high-risk group than in the non-high-risk group (P

Volumetric functional imaging is widely used for recording neuron activities in vivo for many experimental organisms. Here the authors report supervised deep-denoising methods for improved whole-brain imaging, large field-of-view imaging in freely moving animals, and recovering complex neurite structures in C. elegans.

BackgroundColorectal cancer is the third most common cancer worldwide. Colonoscopy is the gold standard for colorectal cancer screening. However, the colonoscopy participation rate in China is much lower than that in Europe and the United States. As only non-sedated colonoscopies are offered in colorectal cancer screening programs in China, the absence of sedation may contribute to this gap.MethodsTo explore the effect of free and partially participant-paid sedated colonoscopy on improving colorectal screening participation, we conducted a cross-sectional study under the framework of the Cancer Screening Program in Urban China in Xuzhou from May 2017 to December 2020. The Quanshan district was set as the control group and provided free non-sedated colonoscopy, the Yunlong district was set as a partial cost coverage group and offered partially participant-paid sedated colonoscopy, and the Gulou district was set as the full cost coverage group and offered free sedation colonoscopies. Multivariate logistic regression was used for multivariate analysis of colonoscopy participation and colorectal lesion detection rates between the groups.ResultsFrom May 2017 to May 2020, 81,358 participants were recruited and completed questionnaire, 7,868 subjects who met high-risk conditions for CRC were invited to undergo colonoscopy. The colonoscopy participation rates in the control group, partially cost coverage, and full cost coverage groups were 17.33% (594/3,428), 25.66% (542/2,112), and 34.41% (801/2,328), respectively. Subjects in the partial and full cost coverage groups had 1.66-fold (95% CI: 1.48–1.86) and 2.49-fold (95% CI: 2.23–2.76) increased rates compared with those in the control group. The adjusted PARs for the partially and the full cost coverage group was 9.08 (95% CI: 6.88–11.28) and 18.97 (95% CI: 16.51–21.42), respectively. The detection rates of CAN in the control, partial-cost coverage, and full-cost coverage groups were 3.54% (21/594), 2.95% (16/542), and 5.12% (41/801), respectively. There were no significant differences in the detection rates between the group. However, sedated colonoscopy increases costs.ConclusionSedated colonoscopy increased colonoscopy participation rates in both the partial and full cost-covered groups. A partial cost coverage strategy may be a good way to increase colorectal cancer participation rates and quickly establish a colorectal cancer screening strategy in underfunded areas.

High-throughput transgenesis using synthetic DNA libraries is a powerful method for systematically exploring genetic function. Diverse synthesized libraries have been used for protein engineering, identification of protein–protein interactions, characterization of promoter libraries, developmental and evolutionary lineage tracking, and various other exploratory assays. However, the need for library transgenesis has effectively restricted these approaches to single-cell models. Here, we present Transgenic Arrays Resulting in Diversity of Integrated Sequences (TARDIS), a simple yet powerful approach to large-scale transgenesis that overcomes typical limitations encountered in multicellular systems. TARDIS splits the transgenesis process into a two-step process: creation of individuals carrying experimentally introduced sequence libraries, followed by inducible extraction and integration of individual sequences/library components from the larger library cassette into engineered genomic sites. Thus, transformation of a single individual, followed by lineage expansion and functional transgenesis, gives rise to thousands of genetically unique transgenic individuals. We demonstrate the power of this system using engineered, split selectable TARDIS sites in Caenorhabditis elegans to generate (1) a large set of individually barcoded lineages and (2) transcriptional reporter lines from predefined promoter libraries. We find that this approach increases transformation yields up to approximately 1000-fold over current single-step methods. While we demonstrate the utility of TARDIS using C. elegans, in principle the process is adaptable to any system where experimentally generated genomic loci landing pads and diverse, heritable DNA elements can be generated.

As social media become increasingly important for science communication, scientists are grappling with their new role on these platforms. While some have called for the increased presence and training of scientists on social media, others prefer to leverage the influence of social media influencers for science communication. This study explores the effects of source identity (scientist or influencer) and self-disclosure type (personal or professional) on perceptions of authenticity and expertise, as well as parasocial interactions. In an online between-subjects experiment ( N = 1579), participants rated scientists on Twitter as more authentic and qualified than influencers, and rated Twitter profiles with professional self-disclosure as more qualified than profiles with personal self-disclosure. Subsequently, participants indicated stronger parasocial interactions, higher information-seeking intentions, and higher prosocial intentions. Anti-intellectualism was found to moderate these relationships. These findings suggest that scientists can employ certain strategies as they seek to establish themselves and reach wider audiences on social media platforms.

With its early start in urbanization, Europe has accumulated a wealth of practical experience in urban agriculture (UA), exploring various development models. This paper compares and analyzes the characteristic patterns of UA in Europe and China through theoretical research, academic frontier exploration, and case analysis. In order to investigate and analyze theoretical developments and the current state of academic frontiers in a systematic, accessible, and comprehensive approach, the methodology of bibliometric analysis has been utilized. A bibliometric method is applied to analyze relevant data from the Web of Science (WoS) core collection database and 2230 CNKI publications. The case study section conducts separate field research on nine representative European practices of urban food gardening and urban farming. Additionally, the study scrutinizes UA research development and its implementation in Hangzhou, China. Based on the findings of this study, the authors recommend that European approaches to the development of UA in China’s future UA practice be taken into account, in particular their methods and strategies for realizing social and cultural benefits. It is imperative to integrate UA projects into urban green space system planning and to rationalize their construction types. Simultaneously, Chinese scholars are encouraged to explore the socio-cultural functions of UA, with a particular focus on urban agricultural heritage conservation.

The development and utilization of saline-alkaline water, an important backup resource, has received widespread attention. However, the underuse of saline-alkaline water, threatened by the single species of saline-alkaline aquaculture, seriously affects the development of the fishery economy. In this work, a 30-day NaHCO3 stress experimental study combined with analyses of untargeted metabolomics, transcriptome, and biochemical approaches was conducted on crucian carp to provide a better understanding of the saline-alkaline stress response mechanism in freshwater fish. This work revealed the relationships among the biochemical parameters, endogenous differentially expressed metabolites (DEMs), and differentially expressed genes (DEGs) in the crucian carp livers. The biochemical analysis showed that NaHCO3 exposure changed the levels of several physiological parameters associated with the liver, including antioxidant enzymes (SOD, CAT, GSH-Px), MDA, AKP, and CPS. According to the metabolomics study, 90 DEMs are involved in various metabolic pathways such as ketone synthesis and degradation metabolism, glycerophospholipid metabolism, arachidonic acid metabolism, and linoleic acid metabolism. In addition, transcriptomics data analysis showed that a total of 301 DEGs were screened between the control group and the high NaHCO3 concentration group, of which 129 up-regulated genes and 172 down-regulated genes. Overall, NaHCO3 exposure could cause lipid metabolism disorders and induce energy metabolism imbalance in the crucian carp liver. Simultaneously, crucian carp might regulate its saline-alkaline resistance mechanism by enhancing the synthesis of glycerophospholipid metabolism, ketone bodies, and degradation metabolism, at the same time increasing the vitality of antioxidant enzymes (SOD, CAT, GSH-Px) and nonspecific immune enzyme (AKP). Herein, all results will provide new insights into the molecular mechanisms underlying the stress responses and tolerance to saline-alkaline exposure in crucian carp.

In cold regions, air entrained concrete has been widely used against freeze–thaw deterioration. This paper studied the influence of curing conditions on the strength and durability of air entrained ordinary portland cement (OPC) and fly ash (FA) concrete. Four different curing conditions including standard curing (SC), air curing (AC), mild temperature curing (MC), and elevated temperature curing (EC) were utilized to cure the cast specimens. The compressive strength at 3, 7, 14, and 28 days was measured respectively. Also, the water absorption, sorptivity, air void system, as well as freeze–thaw durability after 28 days of curing were investigated. Test results suggested that AC condition impeded the strength gain of both concrete, but it affected FA concrete more than OPC concrete. EC condition improved the early-age strength while compromised the later-age strength of OPC concrete, whereas EC condition improved the compressive strength of FA concrete at both early ages and later ages. AC condition has more adverse effects on water absorption as well as sorptivity of FA concrete than those of OPC concrete. EC condition increased the water absorption and sorptivity of OPC concrete, whereas reduced the water absorption and sorptivity of FA concrete. Although the air content in fresh OPC and FA concrete were comparable, FA concrete had less proportion of microvoids (air voids smaller than 300 μm), larger spacing factor but smaller specific surface, regardless of curing conditions. EC condition caused the reduction in air content, the increase of spacing factor, and decrease of specific surface. For both OPC concrete and FA concrete, the four curing conditions produced different freeze–thaw durability factor (DF), but all the specimens passed the failure limit of 60 %. The freeze–thaw test results based on specimens under SC condition may overestimate the DF.

Luminescent materials and optoelectronics, particularly those that rely on down-conversion optical phenomena (i.e., involving a conversion from higher-energy photons into lower-energy photons), have garnered increasing interest in various photonics applications. Over the years, a plethora of down-converting luminescent materials have been actively explored, in particular for enhancing the collection and conversion efficiency of luminescent solar concentrators since the 1980s. However, with the exploration of new down-converting luminescent materials and the recent development of numerous emerging applications utilizing luminescent components for enhanced system performance, the technology is envisaged to expand beyond its use in luminescent solar concentrators. This perspective article aims at shedding light on the significance of incorporating luminescent materials and components for various emerging technologies related to optical-based communication, imaging, tracking, sensing, and data storage and encryption. The related opportunities and challenges are also outlined, which can potentially inspire practical pathways toward the commercialization of luminescent-based optoelectronics and shape the way forward for the broader community.

Abstract Optimization of winding resistance for litz wire inductors is essential to reduce losses and improve energy transfer efficiency in electrical power systems. In this study, an approximate model for the optimization of winding resistance in litz wire inductors based on Dowell's equation is developed in three frequency ranges. The proximity and skin effects are analysed separately and subsequently combined to obtain an approximation with minimum theoretical error. Two error functions are defined to determine the frequency ranges for which the approximation is valid. Based on this Dowell's model approximation, it is found that, with the other parameters of the inductors fixed, both the porosity factor and conductivity have an optimal value that minimizes AC resistance for the litz wire windings. Thus, expressions for the optimum porosity factor and conductivity are derived, the optimization schemes under different practical engineering conditions are also given. The theoretical results are in good agreement with the experimental measurements, which indicates that the proposed model is valid for three frequency ranges, and the proposed optimization method is practical and suitable.

Abstract Instructional feedback has the power to enhance learning. However, learners do not always feel satisfied with their feedback experience. Simultaneously, little attention has been paid on investigating how feedback is implemented in online competency-based learning (CBL). CBL is an approach under which learning activities are organized in a non-linear manner to help learners achieve pre-defined competencies. This study applied a multiple case study method, and 17,266 pieces of the coded feedback text, given by instructors for three learning tasks from a blended undergraduate course, were analyzed. The results showed that instructors implemented 11 types of feedback. Feedback that was used to give praise was less effective, but was frequently used. Regulative feedback and emotional feedback can be very effective, but they were actually rarely used. Feedback for diagnosis, suggesting improvements, and praise was frequently and consistently used across tasks with different complexity. In contrast, feedback used for complementary teaching and time management, as well as emotional feedback were rarely used. Based on the obtained findings, the potential causes and suggestions for improving feedback implementation were discussed.

The Chinese government focuses on the high-end equipment manufacturing industry to achieve a target of carbon neutrality. This study takes China’s Bohai Rim as a case study. First, the Tapio decoupling model was used to analyze the carbon emission status of the high-end equipment manufacturing industry in the Bohai Rim. Second, LMDI was used to determine the main factors of carbon emission. Similarly, the Monte Carlo simulation predicted the time of carbon neutrality. The results found that the relationship between carbon emission and the development of the high-end equipment manufacturing industry is that of strong decoupling, but there is still a risk of “recoupling.” The scale effect is the primary driving force for carbon emission reduction in the equipment manufacturing industry, followed by a structural effect and a carbon emission intensity effect. In the baseline scenario, low-carbon scenario, and technological breakthrough scenario, carbon neutrality will be achieved before 2060. The results of the study suggest that China should improve energy utilization efficiency and encourage green innovation.

Two platinum precursors, Pt(CO)2Cl2 and Pt(CO)2Br2, were designed for focused electron beam-induced deposition (FEBID) with the aim of producing platinum deposits of higher purity than those deposited from commercially available precursors. In this work, we present the first deposition experiments in a scanning electron microscope (SEM), wherein series of pillars were successfully grown from both precursors. The growth of the pillars was studied as a function of the electron dose and compared to deposits grown from the commercially available precursor MeCpPtMe3. The composition of the deposits was determined using energy-dispersive X-ray spectroscopy (EDX) and compared to the composition of deposits from MeCpPtMe3, as well as deposits made in an ultrahigh-vacuum (UHV) environment. A slight increase in metal content and a higher growth rate are achieved in the SEM for deposits from Pt(CO)2Cl2 compared to MeCpPtMe3. However, deposits made from Pt(CO)2Br2 show slightly less metal content and a lower growth rate compared to MeCpPtMe3. With both Pt(CO)2Cl2 and Pt(CO)2Br2, a marked difference in composition was found between deposits made in the SEM and deposits made in UHV. In addition to Pt, the UHV deposits contained halogen species and little or no carbon, while the SEM deposits contained only small amounts of halogen species but high carbon content. Results from this study highlight the effect that deposition conditions can have on the composition of deposits created by FEBID.

Abstract Background Individuals with δβ-thalassemia/HPFH and β-thalassemia usually present with intermedia or thalassemia major. No large-scale survey on HPFH/δβ-thalassemia in southern China has been reported to date. The purpose of this study was to examine the molecular epidemiology and hematologic characteristics of these disorders in Guangzhou, the largest city in Southern China, to offer advice for thalassemia screening programs and genetic counseling. Methods A total of 125,661 couples participated in pregestational thalassemia screening. 654 subjects with fetal hemoglobin (HbF) level ≥ 5% were selected for further investigation. Gap-PCR combined with Multiplex ligation dependent probe amplification (MLPA) was used to screen for β-globin gene cluster deletions. Gene sequencing for the promoter region of HBG1 /HBG2 gene was performed for all those subjects. Results A total of 654 individuals had hemoglobin (HbF) levels≥5, and 0.12% of the couples were found to be heterozygous for HPFH/δβ-thalassemia, including Chinese Gγ (Aγδβ)0-thal, Southeast Asia HPFH (SEA-HPFH), Taiwanese deletion and Hb Lepore–Boston–Washington. The highest prevalence was observed in the Huadu district and the lowest in the Nansha district. Three cases were identified as carrying β-globin gene cluster deletions, which had not been previously reported. Two at-risk couples (0.0015%) were required to receive prenatal diagnosis. We also found 55cases of nondeletional-HPFH (nd-HPFH), including 54 with Italian nd-HPFH and one with the Aγ-197C-T heterozygous state. It is difficult to discriminate between Chinese Gγ (Aγδβ)0-thal and Italian nd-HPFH carriers using hemoglobin (Hb) analysis. Conclusions This study is the first to describe the familial prevalence of HPFH/δβ-thalassemia and the high-risk rate in Greater Guangzhou Area, and the findings will support the implementation of thalassemia screening for three common deletions by gap-PCR. We also presented a systematic description of genotype-phenotype relationships which will be useful for genetic counseling and prenatal diagnostic services for β-thalassemia intermedia.

In order to promote the healthy and rapid development of e-commerce, China launched the construction of National E-commerce Demonstration Cities in 2009. This paper presents a feasible road to achieving sustainable development through the new urban development model. The paper employs the data of 265 cities in China from 2007 to 2016 as a research sample and uses the multiperiod difference-in-difference method to test the impact of National E-commerce Demonstration Cities pilots on urban environmental pollution. The basic result shows that urban environmental pollution is reduced by about 17.5% on average after becoming pilot cities, and the National E-commerce Demonstration Cities policy significantly reduces urban environmental pollution. We adopt a series of robustness tests, and all tests show that the basic result is still robust. Moreover, heterogeneity tests show that the pollution reduction effect of the National E-commerce Demonstration Cities policy in big cities is stronger than in small- and mid-sized cities, and there is no significant difference between the eastern cities and mid-western cities. The pollution reduction effect of the National E-commerce Demonstration Cities policy is more significant in cities with high human capital, low fiscal expenditure, and high information infrastructure. The empirical results of the spatial Dubin model show that the pilot city has no significant spatial spillover to neighboring cities. In the era of rapid development of e-commerce, this study provides a reference for developing countries to improve the urban environment and achieve sustainable development by using the new urban development model integrating e-commerce and urbanization.

Robust and accurate behavioral tracking is essential for ethological studies. Common methods for tracking and extracting behavior rely on user adjusted heuristics that can significantly vary across different individuals, environments, and experimental conditions. As a result, they are difficult to implement in large-scale behavioral studies with complex, heterogenous environmental conditions. Recently developed deep-learning methods for object recognition such as Faster R-CNN have advantages in their speed, accuracy, and robustness. Here, we show that Faster R-CNN can be employed for identification and detection of Caenorhabditis elegans in a variety of life stages in complex environments. We applied the algorithm to track animal speeds during development, fecundity rates and spatial distribution in reproductive adults, and behavioral decline in aging populations. By doing so, we demonstrate the flexibility, speed, and scalability of Faster R-CNN across a variety of experimental conditions, illustrating its generalized use for future large-scale behavioral studies.

AbstractMechanisms that lead to different quantities of hydrocarbon accumulation in complex fault blocks are a major subject that impacts further development plans of oil and gas fields. To better understand such mechanisms, fault activity has been interpreted along with existing electron micrographs from the fault zone, petrophysical data, and the occurrence of the seismic pump. This enabled us to investigate the controlling mechanisms of the growth faults and other associated faults with the main growth fault in the Wang Guantun area that could have impacted hydrocarbon distribution. The results showed that the activity of Kongdong growth fault is periodic and intermittent, which produced strong seismic pumping action. Furthermore, a series of secondary faults were generated in adjacent strata due to the fault activity, which could have led to the formation of a secondary seismic pump source. A combination of these two incidents is believed to influence the differential distribution of hydrocarbons in the area, in fault-associated reservoirs. Ultimately, we correlated the activity of the growth fault to the strength of the pumping force causing the distribution of hydrocarbons in the active parts of the faults (pump source position) on the horizontal plane and vertically located reservoirs to be more dominant.

A composite separator layer in Portland cement concrete pavement, formed by a lower bearing layer and micro surfacing, was seldom used in airport pavement, but it has great application potential. This paper studied the properties of the composite separator layer and its benefits for pavement. The basic properties investigated in the study were resilient modulus and interlayer property between the separator layer and concrete. The resilient modulus of the micro surfacing was tested to calculate the modulus of the whole separation layer. The interlayer shearing test was done on core specimens using a self-developed facility that can apply load in the normal direction. Shearing test results show that temperature affects the shape of the shearing curve and normal stress linearly affects the stable shear force. Additionally, an in-situ erosion test was carried out to prove the anti-scouring property of the separator layer. Furthermore, a finite element model (FEM) model was established to study the influence of the composite separator layer. The FEM employed the modulus test results and the measured interlayer characteristic. The interlayer characteristic was simplified into a two-stage constitutional model. Monitored data on the mechanical response of the pavement structure in an airport validated the FEM model. Results show that the separator layer reduces the chance of contraction crack under the sudden temperature drop in the concrete slab before sawing. FEM results show that though the separator layer slightly increases the tensile stress of concrete, the tensile stress is greatly reduced if the slab develops voids in the future. The most significant benefit of the separation layer is it reduces the chance of void occurrence so that the lifespan of pavement with a separator layer is improved compared to regular pavements which frequently have voids beneath the slab. With the finite element model results and cumulative fatigue life equations, the separator layer was estimated to elongate the pavement service life for years, depending on the time voids appear.

The force-induced unfolding and refolding of proteins is speculated to be a key mechanism in the sensing and transduction of mechanical signals in the living cell. Yet, little evidence has been gathered for its existence in vivo. Prominently, stretch-induced unfolding is postulated to be the activation mechanism of the twitchin/titin family of autoinhibited sarcomeric kinases linked to the mechanical stress response of muscle. To test the occurrence of mechanical kinase activation in living working muscle, we generated transgenic Caenorhabditis elegans expressing twitchin containing FRET moieties flanking the kinase domain and developed a quantitative technique for extracting FRET signals in freely moving C. elegans, using tracking and simultaneous imaging of animals in three channels (donor fluorescence, acceptor fluorescence, and transmitted light). Computer vision algorithms were used to extract fluorescence signals and muscle contraction states in each frame, in order to obtain fluorescence and body curvature measurements with spatial and temporal precision in vivo. The data revealed statistically significant periodic changes in FRET signals during muscle activity, consistent with a periodic change in the conformation of twitchin kinase. We conclude that stretch-unfolding of twitchin kinase occurs in the active muscle, whereby mechanical activity titrates the signaling pathway of this cytoskeletal kinase. We anticipate that the methods we have developed here could be applied to obtaining in vivo evidence for force-induced conformational changes or elastic behavior of other proteins not only in C. elegans but in other animals in which there is optical transparency (e.g., zebrafish).

We report a generic smartphone app for quantitative annotation of complex images. The app is simple enough to be used by children, and annotation tasks are distributed across app users, contributing to efficient annotation. We demonstrate its flexibility and speed by annotating >30,000 images, including features of rice root growth and structure, stem cell aggregate morphology, and complex worm (Caenorhabditis elegans) postures, for which we show that the speed of annotation is >130-fold faster than state-of-the-art techniques with similar accuracy.

We apply topological data analysis to the behavior of C. elegans, a widely studied model organism in biology. In particular, we use topology to produce a quantitative summary of complex behavior which may be applied to high-throughput data. Our methods allow us to distinguish and classify videos from various environmental conditions and we analyze the trade-off between accuracy and interpretability. Furthermore, we present a novel technique for visualizing the outputs of our analysis in terms of the input. Specifically, we use representative cycles of persistent homology to produce synthetic videos of stereotypical behaviors.

Positive parent-adolescent communication has been found to be negatively related to adolescent depressive symptoms; however, few studies have investigated the moderating effects of adolescent gender and age on this relationship, especially during early adolescence in China. The present study investigated the joint moderating effects of adolescent gender and age on the linkage of father-adolescent and mother-adolescent communication with adolescents’ depressive symptoms. A total of 11,455 Chinese junior high school students (Mage = 14.15 years, SD = 1.22 years; 49.86% boys; Ngrade7 = 5712, Ngrade9 = 5743) completed ad hoc questionnaires of parent-adolescent communication and depressive symptoms. Multiple linear regression analyses were conducted. Results indicated that gender and age jointly moderated the association between parental communication and adolescent depressive symptoms. Specifically, for girls, the negative effects of both father-adolescent and mother-adolescent communication on depressive symptoms were stronger in 9th grade students than in 7th grade students, while for boys, the negative effects were not different between 7th grade students and 9th grade students. These findings suggest that in China, the protective effects of positive parent-adolescent communication on adolescents’ depressive symptoms may be most salient among senior-grade girls in junior high school.

Introduction Ankylosing spondylitis (AS) is a recurrent autoimmune disease that is associated with a high disability rate, which has a profound negative impact on daily life. It has been clinically reported that traditional qigong exercise has certain therapeutic advantages in treating AS; however, this postulation is not evidence-based. Therefore, this study will aim at systematically appraising the validity and safety of traditional qigong exercise in treating AS.Methods and analysis We searched the English (PubMed, Embase, Web of Science and the Cochrane Library) and Chinese databases (China National Knowledge Infrastructure, Wan fang, VIP and Chinese biomedical database) for relevant information. Additionally, the Baidu Academic and Google Academic databases were manually searched to mine relevant information. Randomised controlled clinical trials of traditional qigong exercise in treating AS were searched from the establishment of the database to September 2020. Quality articles were extracted and independently evaluated by two researchers before inclusion in this study. Meta-analysis of the included articles was performed using the RevMan V.5.3 software.Ethics and dissemination This study will not involve primary data collection, and formal ethics approval will, therefore, not be required. We aim to publish this systematic review in a peer-reviewed journal.Trial registration number CRD42020207057.

Although identifying cell names in dense image stacks is critical in analyzing functional whole-brain data enabling comparison across experiments, unbiased identification is very difficult, and relies heavily on researchers’ experiences. Here, we present a probabilistic-graphical-model framework, CRF_ID, based on Conditional Random Fields, for unbiased and automated cell identification. CRF_ID focuses on maximizing intrinsic similarity between shapes. Compared to existing methods, CRF_ID achieves higher accuracy on simulated and ground-truth experimental datasets, and better robustness against challenging noise conditions common in experimental data. CRF_ID can further boost accuracy by building atlases from annotated data in highly computationally efficient manner, and by easily adding new features (e.g. from new strains). We demonstrate cell annotation in Caenorhabditis elegans images across strains, animal orientations, and tasks including gene-expression localization, multi-cellular and whole-brain functional imaging experiments. Together, these successes demonstrate that unbiased cell annotation can facilitate biological discovery, and this approach may be valuable to annotation tasks for other systems.

A fundamental challenge complicates news decisions about covering vaccine side effects: although serious vaccine side effects are rare, less severe ones do occur occasionally. The study was designed to test whether a side effect message could induce vaccine hesitancy and whether that could be countered by pro-vaccine messages about vaccine safety. A large (N = 2,345), nationally representative experiment was conducted by randomly exposing participants to one of six videos about the measles, mumps, and rubella (MMR) vaccine edited from news programs produced during the 2019 measles outbreak in the United States. The design was a 2x3 factorial crossing the presence or absence of a hesitancy-inducing narrative message with a pro-vaccine science-supporting message (i.e., no message, science-supporting expert message, or pro-vaccine narrative message), leading to a total of six conditions. A general linear model was used to assess the effects of these videos on respondents' (1) vaccine risk perceptions, (2) policy views on vaccination, (3) willingness to encourage others to vaccinate their children, and (4) intention to send a pro-vaccine letter to their state representative. Findings indicated that the science-supporting expert message about vaccine safety led to higher pro-vaccine evaluations relative to other conditions [e.g., b = -0.17, p < .001, a reduction in vaccine risk perceptions of 0.17 as compared to the control]. There was also suggestive evidence that the hesitancy-inducing narrative may limit the effectiveness of a science-supporting expert message, although this finding was not consistent across different outcomes. When shown alone the hesitancy-inducing narrative did not shift views and intentions, but more research is needed to ascertain whether exposure to such messages can undercut the pro-vaccine influence of science-supporting (expert) ones. All in all, however, it is clear that science-supporting messages are effective and therefore worthwhile in combating vaccine misinformation.

BackgroundIn recent years, many studies have explored the potential prognostic utility of C-reactive protein/albumin ratio (CAR) in patients with gastric cancer (GC), however, the results remain conflicting. We thus performed a meta-analysis to determine the association of CAR and prognosis of GC.MethodsThis meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. PubMed, Web of science, Embase, and Cochrane Library were searched. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS) and cancer-specific survival (CSS) of included studies were pooled to estimate the prognostic value of CAR.ResultsEight studies with a total of 3,216 patients were included in this meta-analysis. High CAR was significantly associated with poor OS (HR = 1.59, 95%CI = 1.36-1.85, pConclusionElevated pretreatment CAR is a prognostic marker of poor OS and CSS in patients with GC. Furthermore, high CAR levels are associated with clinicopathological features reflecting tumor progression.

In wireless rechargeable sensor networks for mobile multimedia services, the multi-hop transmission method is often used to reduce the distance of a single hop to save energy. However, the sensor nodes in special locations always carry more forwarding load,which causes energy holes. These sensor nodes in energy hole have the higher energy consumption and the less residual energy, which makes them very fragile and easy to exhaust energy. If a sensor node dies, the structure of the network will be changed and the original function will be affected. In this paper, an energy-balanced joint routing and charging framework is proposed to balance the energy consumption between sensors. By analyzing the network model, the proposed framework is decomposed into a routing strategy and a charging strategy. Considering the impact of the routing structure on sensors energy consumption, the goal of the routing strategy is designed to optimize the routing tree corresponding to the mobile charger staying at each sensor node. Furthermore, the proposed charging strategy prefers the charging path with the best balance of the total energy consumption of sensor nodes during one charging trip. In order to solve these optimization problems, the simulated annealing algorithms, including the proposed random solution generation method and acceptance rules, are used to obtain a fast convergence. The simulation results show that the proposed joint routing and charging framework has better energy balance performance than the traditional scheme.

Over long evolutionary timescales, major changes to the copy number, function, and genomic organization of genes occur, however, our understanding of the individual mutational events responsible for these changes is lacking. In this report, we study the genetic basis of adaptation of two strains of C. elegans to laboratory food sources using competition experiments on a panel of 89 recombinant inbred lines (RIL). Unexpectedly, we identified a single RIL with higher relative fitness than either of the parental strains. This strain also displayed a novel behavioral phenotype, resulting in higher propensity to explore bacterial lawns. Using bulk-segregant analysis and short-read resequencing of this RIL, we mapped the change in exploration behavior to a spontaneous, complex rearrangement of the rcan-1 gene that occurred during construction of the RIL panel. We resolved this rearrangement into five unique tandem inversion/duplications using Oxford Nanopore long-read sequencing. rcan-1 encodes an ortholog to human RCAN1/DSCR1 calcipressin gene, which has been implicated as a causal gene for Down syndrome. The genomic rearrangement in rcan-1 creates two complete and two truncated versions of the rcan-1 coding region, with a variety of modified 5' and 3' non-coding regions. While most copy-number variations (CNVs) are thought to act by increasing expression of duplicated genes, these changes to rcan-1 ultimately result in the reduction of its whole-body expression due to changes in the upstream regions. By backcrossing this rearrangement into a common genetic background to create a near isogenic line (NIL), we demonstrate that both the competitive advantage and exploration behavioral changes are linked to this complex genetic variant. This NIL strain does not phenocopy a strain containing an rcan-1 loss-of-function allele, which suggests that the residual expression of rcan-1 is necessary for its fitness effects. Our results demonstrate how colonization of new environments, such as those encountered in the laboratory, can create evolutionary pressure to modify gene function. This evolutionary mismatch can be resolved by an unexpectedly complex genetic change that simultaneously duplicates and diversifies a gene into two uniquely regulated genes. Our work shows how complex rearrangements can act to modify gene expression in ways besides increased gene dosage.

This data is generated from the analysis of similarities and differences in gene expression levels and pathways among genes (VegfA, VegfB, VegfC, and Pgf) in Vegf family using whole genome expression data generated from normal retina of eighty strains of mice. The results have been published in doi:10.1016/j.exer.2018.06.024 (Cui et al., 2018) [1]. Fig. 1 shows the expression quantitative trait loci (eQTL) that regulate the expression level of each gene in the Vegf family. The other three figure show the overlapped genes among the top 500 genes that their expression levels are most closely correlated to each of the Vegf genes. The four tables contain the information of top 50 genes that their expression levels are most closely correlated to each of the Vegf genes, and the correlation of the top 50 genes from one gene to the other genes in the Vegf family. Keywords: Vegf family, eQTL, Mouse retina, Gene relationship, Expression levels

Influenza hemagglutinin (HA) is considered a major protective antigen of seasonal influenza vaccine but antigenic drift of HA necessitates annual immunizations using new circulating HA versions. Low variation found within conserved non-HA influenza virus (INFV) antigens may maintain protection with less frequent immunizations. Conserved antigens of influenza A virus (INFV A) that can generate cross protection against multiple INFV strains were evaluated in BALB/c mice using modified Vaccinia virus Ankara (MVA)-vectored vaccines that expressed INFV A antigens hemagglutinin (HA), matrix protein 1 (M1), nucleoprotein (NP), matrix protein 2 (M2), repeats of the external portion of M2 (M2e) or as tandem repeats (METR), and M2e with transmembrane region and cytoplasmic loop (M2eTML). Protection by combinations of non-HA antigens was equivalent to that of subtype-matched HA. Combinations of NP and forms of M2e generated serum antibody responses and protected mice against lethal INFV A challenge using PR8, pandemic H1N1 A/Mexico/4108/2009 (pH1N1) or H5N1 A/Vietnam/1203/2004 (H5N1) viruses, as demonstrated by reduced lung viral burden and protection against weight loss. The highest levels of protection were obtained with NP and M2e antigens delivered as MVA inserts, resulting in broadly protective immunity in mice and enhancement of previous natural immunity to INFV A.

The Ras pathway patterns the poles of the Drosophila embryo by downregulating the levels and activity of a DNA-binding transcriptional repressor Capicua (Cic). We demonstrate that the spatiotemporal pattern of Cic during this signaling event can be harnessed for functional studies of mutations in the Ras pathway in human diseases. Our approach relies on a new microfluidic device that enables parallel imaging of Cic dynamics in dozens of live embryos. We found that although the pattern of Cic in early embryos is complex, it can be accurately approximated by a product of one spatial profile and one time-dependent amplitude. Analysis of these functions of space and time alone reveals the differential effects of mutations within the Ras pathway. Given the highly conserved nature of Ras-dependent control of Cic, our approach provides new opportunities for functional analysis of multiple sequence variants from developmental abnormalities and cancers.

To facilitate precise and convenient control of biological sample temperature, we developed a low-cost device that can be used independently or with any stereomicroscope. The purpose of the device is to control the thermal environment during experimental intervals in which a specimen must be manipulated outside of an incubator, e.g. for dissection or slide-mounting in preparation for imaging. Sample temperatures can be both cooled to below and heated to above room temperatures, and stably maintained at a precision of +/- 0.1˚C. To demonstrate the utility of this device, we report improved characterization of the penetrance of a short-acting temperature-sensitive allele in C. elegans embryos, and identification of the upper temperature threshold for embryonic viability for six Caenorhabditis species. By controlling the temperature environment even as a specimen is manipulated, this device offers consistency and flexibility, reduces environmental noise, and enables precision timing in experiments requiring temperature shifts.

Experimenter scoring of cellular imaging data can be biased. This study describes an automated and unbiased multidimensional phenotyping method that relies on machine learning and complex feature computation of imaging data, and identifies weak alleles affecting synapse morphology in live C. elegans.

Kinesin motor proteins transport intracellular cargoes throughout cells by hydrolyzing ATP and moving along microtubule tracks. Intramolecular autoinhibitory interactions have been shown for several kinesins in vitro; however, the physiological significance of autoinhibition remains poorly understood. Here, we identified four mutations in the stalk region and motor domain of the synaptic vesicle (SV) kinesin UNC-104/KIF1A that specifically disrupt autoinhibition. These mutations augment both microtubule and cargo vesicle binding in vitro. In vivo, these mutations cause excessive activation of UNC-104, leading to decreased synaptic density, smaller synapses, and ectopic localization of SVs in the dendrite. We also show that the SV-bound small GTPase ARL-8 activates UNC-104 by unlocking the autoinhibition. These results demonstrate that the autoinhibitory mechanism is used to regulate the distribution of transport cargoes and is important for synaptogenesis in vivo.

Introduction. To compare the effect and safety of intravitreal conbercept (IVC), intravitreal ranibizumab (IVR), or intravitreal triamcinolone acetonide (IVTA) injection on 23-gauge (23-G) pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR). Methods. Fifty patients (60 eyes) of varying degrees of PDR were randomly grouped into 3 groups (1 : 1 : 1) (n=20 in each group). The 23-G PPV was performed with intravitreal conbercept or ranibizumab injection 3–7 days before surgery or intravitreal TA injection during surgery. The experiment was randomized controlled, with a noninferiority limit of five letters. Main outcome measures included BCVA, operation time, incidence of iatrogenic retinal breaks, endodiathermy rate, and silicone oil tamponade. Results. At 6 months after surgery, there were no significant differences of BCVA improvements, operation time, incidence of iatrogenic retinal breaks, endodiathermy rate, silicone oil tamponade, vitreous clear-up time, and the incidence of intraoperative bleeding between the IVC and IVR groups (all P values ≥ 0.05), but they were significantly different from the IVTA group (all P values < 0.05). IOP increases did not show significant differences between the IVC and IVR groups, but both were significantly different with the IVTA group. More patients had higher postoperative IOP in the IVTA group. Conclusions. The intravitreal injection of conbercept, ranibizumab, or TA for PDR had a significant different effect on outcomes of 23-G PPV surgery. Conbercept and ranibizumab can reduce difficulty of the operation, improve the success rate of PPV surgery, and decrease the incidence of postoperative complications.