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Several recent cryo‐electron microscopy (cryo‐EM) studies about the eukaryotic primosome, including the human primosome described by Yin et al. in this issue, have uncovered the structural intricacies between the RNA primase and the DNA polymerase. These studies show that these two partners tango on DNA to synthesize a hybrid primer composed of ~ 10 nucleotide (nt) RNA and ~ 10‐nt DNA. They reveal key intermediate steps involved in this process; from the self‐inhibited apo state to the initiation of RNA primer synthesis, RNA primer handover to the polymerase, primer elongation by polymerase, and finally, primer termination and release. Remarkably, the polymerase domain orchestrates all major steps during primer synthesis. [ABSTRACT FROM AUTHOR]

As the boom of data storage and processing, brain-inspired computing provides an effective approach to solve the current problem. Various emerging materials and devices have been reported to promote the development of neuromorphic computing. Thereinto, the neuromorphic device represented by memristor has attracted extensive research due to its outstanding property to emulate the brain's functions from synaptic plasticity, sensory-memory neurons to some intelligent behaviors of living creatures. Herein, we mainly review the progress of these brain functions mimicked by neuromorphic devices, concentrating on synapse (i.e. various synaptic plasticity trigger by electricity and/or light), neurons (including the various sensory nervous system) and intelligent behaviors (such as conditioned reflex represented by Pavlov's dog experiment). Finally, some challenges and prospects related to neuromorphic devices are presented. [ABSTRACT FROM AUTHOR]

This study assessed the cost-effectiveness of different diabetic retinopathy (DR) screening strategies in rural regions in China by using a Markov model to make health economic evaluations. In this study, we determined the structure of a Markov model according to the research objectives, which required parameters collected through field investigation and literature retrieval. After perfecting the model with parameters and assumptions, we developed a Markov decision analytic model according to the natural history of DR in TreeAge Pro 2011. For this model, we performed Markov cohort and cost-effectiveness analyses to simulate the probabilistic distributions of different developments in DR and the cumulative cost-effectiveness of artificial intelligence (AI)-based screening and ophthalmologist screening for DR in the rural population with diabetes mellitus (DM) in China. Additionally, a model-based health economic evaluation was performed by using quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios. Last, one-way and probabilistic sensitivity analyses were performed to assess the stability of the results. From the perspective of the health system, compared with no screening, AI-based screening cost more (the incremental cost was 37,257.76 RMB (approximately 5,211.31 US dollars)), but the effect was better (the incremental utility was 0.33). Compared with AI-based screening, the cost of ophthalmologist screening was higher (the incremental cost was 14,886.76 RMB (approximately 2,070.19 US dollars)), and the effect was worse (the incremental utility was -0.31). Compared with no screening, the incremental cost-effectiveness ratio (ICER) of AI-based DR screening was 112,146.99 RMB (15,595.47 US dollars)/QALY, which was less than the threshold for the ICER (< 3 times the per capita gross domestic product (GDP), 217,341.00 RMB (30,224.03 US dollars)). Therefore, AI-based screening was cost-effective, which meant that the increased cost for each additional quality-adjusted life year was merited. Compared with no screening and ophthalmologist screening for DR, AI-based screening was the most cost-effective, which not only saved costs but also improved the quality of life of diabetes patients. Popularizing AI-based DR screening strategies in rural areas would be economically effective and feasible and can provide a scientific basis for the further formulation of early screening programs for diabetic retinopathy. [ABSTRACT FROM AUTHOR]

In this article, we present a flexible model for microbiome count data. We consider a quasi‐likelihood framework, in which we do not make any assumptions on the distribution of the microbiome count except that its variance is an unknown but smooth function of the mean. By comparing our model to the negative binomial generalized linear model (GLM) and Poisson GLM in simulation studies, we show that our flexible quasi‐likelihood method yields valid inferential results. Using a real microbiome study, we demonstrate the utility of our method by examining the relationship between adenomas and microbiota. We also provide an R package "fql" for the application of our method. [ABSTRACT FROM AUTHOR]

Background: Autonomic remodeling of the atria plays a pivotal role in the development of atrial fibrillation (AF) and exerts a substantial influence on the progression of this condition. Hyperlipidemia is a predisposing factor for AF, but its effect on atrial nerve remodeling is unclear. The primary goal of this study was to explore the possible mechanisms through which the consumption of a high-fat diet (HFD) induces remodeling of atrial nerves, and to identify novel targets for clinical intervention. Methods: Cell models were created in vitro by subjecting cells to palmitic acid (PA), while rat models were established by feeding them a high-fat diet. To investigate the interplay between cardiomyocytes and nerve cells in a co-culture system, we utilized Transwell cell culture plates featuring a pore size of 0.4 μm. The CCK-8 assay was employed to determine cell viability, fluorescent probe DCFH-DA and flow cytometry were utilized for measuring ROS levels, JC-1 was used to assess the mitochondrial membrane potential, the Griess method was employed to measure the nitric oxide (NO) level in the supernatant, a fluorescence-based method was used to measure ATP levels, and MitoTracker was utilized for assessing mitochondrial morphology. The expression of pertinent proteins was evaluated using western blotting (WB) and immunohistochemistry techniques. SNAP was used to treat nerve cells in order to replicate a high-NO atmosphere, and the level of nitroso was assessed using the iodoTMT reagent labeling method. Results: The study found that cardiomyocytes' mitochondrial morphology and function were impaired under high-fat stimulation, affecting nitric oxide (NO) production through the CRIF1/SIRT1/eNOS axis. In a coculture model, overexpression of eNOS in cardiomyocytes increased NO expression. Moreover, the increased Keap1 nitrosylation within neuronal cells facilitated the entry of Nrf2 into the nucleus, resulting in an augmentation of P21 transcription and a suppression of proliferation. Atrial neural remodeling occurred in the HFD rat model and was ameliorated by increasing myocardial tissue eNOS protein expression with trimetazidine (TMZ). Conclusions: Neural remodeling is triggered by high-fat stimulation, which decreases the production of NO through the CRIF1/eNOS/P21 axis. Additionally, TMZ prevents neural remodeling and reduces the occurrence of AF by enhancing eNOS expression. [ABSTRACT FROM AUTHOR]

Atrial structural remodeling takes on a critical significance to the occurrence and maintenance of atrial fibrillation (AF). As revealed by recent data, insulin-like growth factor-1 receptor (IGF-1R) plays a certain role in tissue fibrosis. In this study, the mechanism of IGF-1R in atrial structural remodeling was examined based on in vivo and in vitro experiments. First, cluster analysis of AF hub genes was conducted, and then the molecular mechanism was proposed by which IGF-1R regulates myocardial fibrosis via the PI3K/Akt/FoxO3a pathway. Subsequently, the mentioned mechanism was verified in human cardiac fibroblasts (HCFs) and rats transduced with IGF-1 overexpression type 9 adeno-associated viruses. The results indicated that IGF-1R activation up-regulated collagen Ⅰ protein expression and Akt phosphorylation in HCFs and rat atrium. The administration of LY294002 reversed the above phenomenon, improved the shortening of atrial effective refractory period, and reduced the increased incidence of AF and atrial fibrosis in rats. The transfection of FoxO3a siRNA reduced the anti-fibrotic effect of LY294002 in HCFs. The above data revealed that activation of IGF-1R takes on a vital significance to atrial structural remodeling by facilitating myocardial fibrosis and expediting the occurrence and maintenance of AF through the regulation of the PI3K/Akt/FoxO3a signaling pathway. [ABSTRACT FROM AUTHOR]

Cross-linking mass spectrometry (XL-MS) is widely used in the analysis of protein structure and protein–protein interactions (PPIs). Throughout the entire workflow, the utilization of cross-linkers and the interpretation of cross-linking data are the core steps. In recent years, the development of cross-linkers and analytical software mostly follow up on the classical models of non-cleavable cross-linkers such as BS3/DSS and MS-cleavable cross-linkers such as DSSO. Although such a paradigm promotes the maturity and robustness of the XL-MS field, it confines the innovation and flexibility of new cross-linkers and analytical software. This critical insight will discuss the classification, advantages, and disadvantages of existing data analysis search engines. Take the new platinum-based metal cross-linker as an example, potential pitfalls in characterization of cross-linked peptides using existing software are discussed. Finally, ideas on developing more flexible, comprehensive, and user-friendly cross-linkers and software tools are proposed. [ABSTRACT FROM AUTHOR]

Background: Over recent decades, autism spectrum disorder (ASD) has been of increasing epidemiological importance, given the substantial increase in its prevalence; at present, clinical diagnosis is possible only after 2 years of age. In this study, we sought to develop a potential predictive model for ASD screening. Methods: We conducted a longitudinal follow-up study of newborns over 3 years. We measured transcript levels of 4 genes (superoxide dismutase-2 [ SOD2 ], retinoic acid–related orphan receptor-α [ RORA ], G protein–coupled estrogen receptor-1 [ GPER ], progesterone receptor [ PGR ]), 2 oxidative stress markers and epigenetic marks at the RORA promoter in case–control umbilical cord blood mononuclear cell (UCBMC) samples. Results: We followed 2623 newborns; we identified 41 children with ASD, 63 with delayed development and 2519 typically developing children. We matched the 41 children with ASD to 41 typically developing children for UCBMC measurements. Our results showed that children with ASD had significantly higher levels of H3K9me3 histone modifications at the RORA promoter and oxidative stress in UCBMC than typically developing children; children with delayed development showed no significant differences. Children with ASD had significantly lower expression of SOD2 , RORA and GPER , but higher PGR expression than typically developing children. We established a model based on these 4 candidate genes, and achieved an area under the curve of 87.0% (standard deviation 3.9%) with a sensitivity of 1.000 and specificity of 0.854 to predict ASD in UCBMC. Limitations: Although the gene combinations produced a good pass/fail cut-off value for ASD evaluation, relatively few children in our study sample had ASD. Conclusion: The altered gene expression in UCBMC can predict later autism development, possibly providing a predictive model for ASD screening immediately after birth. [ABSTRACT FROM AUTHOR]

Pediatric pneumonia is an infectious lung disease with high morbidity and mortality. Sinomenine, an alkaloid extracted from Caulis Sinomenii, exerts anti‐inflammatory and anti‐apoptotic activities. Lipopolysaccharide (LPS) is widely used for the establishment of an inflammatory model. This research aimed to explore the influences of sinomenine on LPS‐caused inflammatory injuries in fetal lung WI‐38 cells. WI‐38 cells were treated with LPS to establish a cellular model of pediatric pneumonia. Cell viability was evaluated using CCK‐8 assay. Apoptosis was evaluated using TUNEL staining and caspase‐3 activity assays. Inflammatory cytokines and NF‐κB p65 phosphorylation levels were measured by Enzyme‐Linked Immunosorbent Assay. Glutathione S‐transferase M1 (GSTM1) expression was detected by western blotting. Results showed that LPS reduced WI‐38 cell viability, and sinomenine protected cells against LPS‐induced viability reduction. Sinomenine concentration‐dependently attenuated LPS‐induced inflammation by reducing TNF‐α, IL‐1β and MCP‐1, and increasing IL‐10 levels. Sinomenine mitigated LPS‐induced apoptosis. GSTM1 was screened by matching the targets of sinomenine and pediatric pneumonia. GSTM1 was upregulated in LPS‐treated WI‐38 cells, and this effect was attenuated after sinomenine treatment. GSTM1 was upstream of NF‐κB pathway. Overexpression of GSTM1 reversed the suppressive functions of sinomenine on LPS‐stimulated inflammation and apoptosis. Overall, sinomenine attenuates inflammation and apoptosis in WI‐38 cells stimulated by LPS via inhibiting GSTM1 expression, indicating the therapeutic potential of sinomenine in pediatric pneumonia. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) infection is a major global health problem of widespread concern. Clinically, serological assays are the most widely used diagnostic tests for HBV infection, with the presence of HBsAg in the serum being indicative of acute and chronic hepatitis B infection. However, increased identification of HBV DNA positive but HBsAg negative cases has greatly promoted the use of molecular assays for more accurate HBV diagnosis. Over the past few decades, especially since the outbreak of COVID-19, significant advancements have been made in the techniques and devices for nucleic acid testing (NAT). Nowadays, the mainstream NAT techniques can broadly be split into two categories: PCR-based methods and non-PCR-based isothermal amplification methods. As achieving point-of-care testing (POCT) or on-site testing is an important development tendency for the next-generation NAT, non-PCR-based isothermal amplification methods like nucleic acid sequence-based amplification (NASBA), rolling circle amplification (RCA), loop-mediated isothermal amplification (LAMP), helicase-dependent amplification (HDA), and recombinase polymerase amplification (RPA) have garnered significant attention in recent years. In this review, we provide a comprehensive overview of the nucleic acid isothermal amplification technologies currently used for HBV detection. The analytical performances of different methods are compared and their integration with microfluidics, lateral flow assays, and CRISPR/Cas systems is also discussed. [ABSTRACT FROM AUTHOR]

Clamp loaders are pentameric AAA+ assemblies that use ATP to open and close circular DNA sliding clamps around DNA. Clamp loaders show homology in all organisms, from bacteria to human. The eukaryotic PCNA clamp is loaded onto 3′ primed DNA by the replication factor C (RFC) hetero‐pentameric clamp loader. Eukaryotes also have three alternative RFC‐like clamp loaders (RLCs) in which the Rfc1 subunit is substituted by another protein. One of these is the yeast Rad24‐RFC (Rad17‐RFC in human) that loads a 9‐1‐1 heterotrimer clamp onto a recessed 5′ end of DNA. Recent structural studies of Rad24‐RFC have discovered an unexpected 5′ DNA binding site on the outside of the clamp loader and reveal how a 5′ end can be utilized for loading the 9‐1‐1 clamp onto DNA. In light of these results, new studies reveal that RFC also contains a 5′ DNA binding site, which functions in gap repair. These studies also reveal many new features of clamp loaders. As reviewed herein, these recent studies together have transformed our view of the clamp loader mechanism. [ABSTRACT FROM AUTHOR]

Motivation As the resolution of metagenomic analysis increases, the evolution of microbial genomes in longitudinal metagenomic data has become a research focus. Some software has been developed for the simulation of complex microbial communities at the strain level. However, the tool for simulating within-strain evolutionary signals in longitudinal samples is still lacking. Results In this study, we introduce STEMSIM, a user-friendly command-line simulator of short-term evolutionary mutations for longitudinal metagenomic data. The input is simulated longitudinal raw sequencing reads of microbial communities or single species. The output is the modified reads with within-strain evolutionary mutations and the relevant information of these mutations. STEMSIM will be of great use for the evaluation of analytic tools that detect short-term evolutionary mutations in metagenomic data. Availability and implementation STEMSIM and its tutorial are freely available online at https://github.com/BoyanZhou/STEMSim. [ABSTRACT FROM AUTHOR]

• Head-on glass microsphere droplet collision is investigated numerically. • Three regime outcomes and five states are discussed. • The critical Weber numbers between different regimes are presented. • Detailed interaction mechanisms of collision outcome scenarios are analyzed. The collision of molten glass microsphere droplets represents a fundamental phenomenon in spheronization, yet a comprehensive understanding of this process remains elusive. A numerical simulation is conducted to investigate the head-on collision dynamics of two molten glass microsphere droplets at varying Weber numbers, by integrating the level set and volume of fluid methods. Three distinct collision regimes are identified: merging, separation into satellite-free droplets, and separation leading to the formation of satellite droplets. Furthermore, the critical Weber numbers delineating the different regimes are presented. Examination of axial and radial variations in the droplets reveals the existence of five distinct states spanning the three collision regimes. The distribution of external vortices around the droplets directly influences the outcomes of droplet collisions. High-pressure regions and high-pressure liquid bridges within droplets serve as key factors in determining the merging or separation of the droplets. Region of high pressure at the end of the liquid bridge acts as a critical indicator for distinguishing between collision separations with and without satellite droplet generation. Observations of velocity and pressure distributions in separations that produce satellite droplets are consistent with the end pinch-off mechanism. This study holds significant implications for controlling high sphericity during the spheronization of glass microsphere droplets. [ABSTRACT FROM AUTHOR]

Circadian dysregulation associates with numerous diseases including metabolic dysfunction, sleep disorder, depression and aging. Given that declined circadian amplitude is a trait commonly found with compromised health, interventions that design in precluding circadian amplitude from dampening will aid to mitigate complex, circadian-related diseases. Here we identify a neurogenic small molecule ISX-9 that is able to support persistent and higher amplitude of circadian oscillations. ISX-9 improves diurnal metabolic rhythms in middle-aged mice. Moreover, the ISX-9-treated mice show better sleep homeostasis with increased delta power during the day time and higher locomotive activity in the dark period. ISX-9 augments CaMKIIδ expression and increases BMAL1 activity via eliciting CaMKIIδ-mediated phosphorylation on BMAL1 residues S513/S515/S516, accordingly composes a positive feedback effect on enhancing circadian amplitude. CaMKIIδ-targeting, and the use of ISX-9 may serve as decent choices for treating circadian-related disorders. Circadian modulators that exert amplitude-enhancing activity using highthroughput compound screening of small molecules identifies ISX-9, which is shown to augment CaMKIIδ expression, increasing BMAL1 activity via CaMKIIδ-dependent phosphorylation. [ABSTRACT FROM AUTHOR]

As more and more people love football and participate in more and more football matches, the physical injuries in the confrontation are getting more and more serious. In recent years, bionic photothermal nanomaterials have shown great application potential in disease treatment. Biomimetic photothermal nanomaterials are functional and intelligent materials with special excellent performance that are designed and synthesized by using natural biomimetic principles. Photothermal therapy (PTT) technology is a new treatment technology in recent years. On the one hand, photothermal therapy technology can convert light energy into heat energy through photothermal conversion factor (PTCA). Molecular water-soluble drugs penetrate into the skin to replace the existing injection administration methods with higher risk and low patient compliance and oral administration methods that generally cause first-pass effects, improve the utilization and efficiency of drugs, and can give provide patients with better treatment. The purpose of this article is to explore the application of the photothermal effect of bionic nanomaterials in the treatment of football sports injuries. The method adopted in this paper is to synthesize different bionic photothermal nanomaterials and synthesize bionic photothermal nanomaterials that are fused with cell membranes, thereby promoting the application of photothermal therapy technology in the treatment of sports injuries; further, by synthesizing bionics wrapped by fusion membranes, photothermal nanomaterials introduce collaborative photothermal therapy technology. The experimental results show that the photothermal effect of nanobiomimetic materials is used to treat common injuries caused by football sports. Compared with traditional treatment methods, HA-CuS gel and near-infrared treatment are applied to the skin with the injured tissue of the experimental group. It dropped to 85.7% in 2 h then gradually dropped to 84.2%, and the recovery speed was significantly accelerated. [ABSTRACT FROM AUTHOR]

Waste like air pollution control (APC) residues from incineration are potentially valuable resources. This paper reports the application of enhanced electrokinetic (EK) treatment processing to APC residues using an approaching anode coupled with a permeable reactive barrier (PRB). The changes of heavy metals (HMs) leaching risk and the effect of EK on metals extractability were explored for the possibilities of treated APC residues and metals recovery. The impact of various factors on HMs leaching was evaluated through response surface experiments. The adsorption ability of PRB and H+ provided by approaching anode could alleviate HMs accumulation during treatment caused by high pH and buffer capacity. Compared with conventional EK treatment, the HMs extraction and leaching reduction improved significantly, with more than 30% energy saved after enhanced EK treatment. The best HMs leaching reduction was obtained after 16 days treatment at 1.97 V/cm of voltage gradient with 14.64 g modified activated carbon used as PRB while the anode was moved after 6.35 days. The results showed fraction conversions could increase the extractability of HMs with the electric field application, and the environmental risk of remaining HMs was reduced through the effective removal of HMs with potential risk after enhanced EK treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • A colorimetric Direct-LAMP assay for Pinelliae Rhizoma and adulterant was developed. • The direct lysis method allows for sample DNA release within 2 min. • A high specificity and sensitivity was achieved by this new assay. • The dual-color changes display a visually dynamic and captivating detection process. • The developed direct-LAMP was successfully validated across 48 actual samples. Pinelliae Rhizoma , renowned for its medicinal benefits against cough, insomnia and inflammation, is frequently utilized in botanical dietary supplements and herbal products. However, due to high demand, there is a risk of adulteration. This study introduced Direct-Loop-Mediated Isothermal Amplification (Direct-LAMP), a rapid colorimetric technique, for distinguishing Pinelliae Rhizoma from its primary adulterant, Rhizoma Typhonii Flagelliformis. This method comprises three parts: DNA extraction-free direct lysis, isothermal amplification and prompt color development. The direct lysis process allows for release of genomic DNA within 2 min. The isothermal amplification reaction exhibits excellent analytical performance, detecting Pinelliae Rhizoma at levels as low as 0.1 pg and Rhizoma Typhonii Flagelliformis at 0.08 ng, while also demonstrating good linearity across a wide range, making it suitable for quantitative analysis. Two different color reagents are employed for these two different plant materials, resulting in dual-color changes for captivating visual detection. The developed direct-LAMP was also successfully validated across 48 actual samples. [ABSTRACT FROM AUTHOR]

In the post-epidemic era, the prevalence of remote collaborations in modern work environments highlight the importance of e-voting as a critical component in facilitating distributed decision-making. Most of the existing e-voting systems heavily rely on a centralized tally authority which requires a high degree of moral trust. However, this kind of architecture is insufficient for expected decentralization and verifiability in remote decision-making. A self-tallying e-voting system is more in line with our developed demands, nonetheless, it suffers adaptive and abortive issues inherently and as a result, fairness cannot be guaranteed. In this paper, we try to provide rational trust by building a blockchain-based self-tallying e-voting system with public traceability. We improve fairness and achieve a balance between privacy and accountability by taking advantage of a time-lock puzzle and traceable ring signature, in which the puzzle-solving time does not impose a real burden. We propose a concrete construction and prove that our protocol satisfies time-limited ballot secrecy, anonymity, exculpability, public traceability, self-tallying and fairness. We implement the prototype both on-chain and off-chain, and the results of time overhead of each phase demonstrate the practicability of our proposal. • Propose a self-tallying e-voting with public traceability based on blockchain. • Introduce a traceable ring signature to balance the anonymity and accountability. • Prove a detailed security proof for the protocol. • Evaluate the time cost of off-chain functions and on-chain functions. [ABSTRACT FROM AUTHOR]

• A magnetic-fluorescent immunosensing platform for efficient detection of ZEN in cereal products was developed. • MIL-53(Al)@AuNPs heterogeneous composite were facilely synthesized to prepare fluorescent signal probe. • The capture probe (MNPs-mAbs) was used to capture the target ZEN rapidly and simplify the immunoassay process. • This MOF-based magnetic-fluorescent immunoassay can rapidly detect ZEN contaminant with a LOD of 0.0035 ng/mL. Rapid, sensitive, specific and stable detection of mycotoxin in food remains an extremely crucial issue. Herein, a magnetic-fluorescent immunosensing platform for the detection of zearalenone (ZEN) was proposed. The platform utilized Au nanoparticles (AuNPs) heterogeneous fluorescent metal–organic framework (MIL-53(Al)@AuNPs) labeled with ZEN-bovine serum albumin (ZEN-BSA) as signal probe and ZEN mono-antibodies coupled with magnetic NPs (MNPs-mAbs) as capture probe. Specifically, the heterogenization of AuNPs on the MIL-53(Al) surface improved its biocompatibility, and facilitated the loading of ZEN-BSA conjugates. The MNPs-mAbs could rapidly capture the target ZEN, simplify the immunoassay process and further improve the detection efficiency. The established competitive magnetic-fluorescent immunosensing platform had a wider linear response to ZEN in the range of 0.001–100 ng/mL with a lower limit of detection (LOD) at 0.0035 ng/mL, and could finish the whole detection process within 20 min, showing great potential for rapid and sensitive detection of food contaminants. [ABSTRACT FROM AUTHOR]

The transmembrane α‐helices of membrane proteins are in general highly hydrophobic, and they enter the lipid bilayer through a lateral gate in the Sec61 translocon. However, some transmembrane α‐helices are less hydrophobic and form membrane channels or substrate‐binding pockets. Insertion of these amphipathic transmembrane α‐helices into the membrane requires the specific membrane‐embedded insertase called the endoplasmic reticulum membrane complex (EMC), which is a multi‐subunit chaperone distinct from the GET insertase complex. Four recent cryo‐electron microscopy studies on the eukaryotic EMC have revealed their remarkable architectural conservation from yeast to humans; a general consensus on the substrate transmembrane helix‐binding pocket; and the evolutionary link to the prokaryotic insertases of the tail‐anchored membrane proteins. These structures provide a solid framework for future mechanistic investigation. [ABSTRACT FROM AUTHOR]

Polymerase sliding clamps are ring‐shaped proteins that encircle duplex DNA and hold polymerases to DNA for high processivity during synthesis. The crystal structure of clamp‐DNA complex reveals that the DNA is highly tilted through the clamp with extensive interaction with the clamp inner surface. In contrast to the tilted clamp‐DNA interaction without DNA polymerases, recent structures of replicative polymerases of bacteria, eukaryotes, and archaea that are bound to the clamp and DNA show that the polymerase positions DNA straight through the clamp without direct protein‐DNA contacts. Instead, the clamp‐to‐DNA interaction is mediated by one or two layers of water. Hence, clamps 'water skate' on DNA during function with replicative polymerases from all domains of life, providing a nearly frictionless bearing for fast and processive DNA synthesis. [ABSTRACT FROM AUTHOR]

We report a thermodynamically driven metal diffusion strategy for the controlled synthesis of high-entropy alloy (HEA) nanocrystals using electrospun carbon nanofibers (CNFs) as nanoreactors. This conceptual pathway is resistant to high temperatures and produces a series of medium-entropy alloy (MEA) and HEA nanocrystals supported on CNFs by adjusting the numbers and kinds of elements. The FeCoNiCrMn/CNFs obtained the lowest overpotential of 345 mV at 50 mA cm−2 compared to MEA. The operando electrochemical Raman results indicate that the enhanced electron transfer from low-electronegativity Fe, Ni, Cr and Mn to the orbit of the Co atom makes Co a local negative charge center, leading to the decrease in absorption energy of OH. [ABSTRACT FROM AUTHOR]

• A highly selective and efficient MIPs were developed for the extraction of CGA. • Computational simulation was exploited to screen optimal synthesis ratio of MIPs. • Simpler preparation, stronger extraction and enrichment and lower cost of MIPs. • Good adsorption performance (Q = 14.85 mg g−1, IF =1.74) and thermal stability of MIPs. Chlorogenic acid (CGA) is an active ingredient in honeysuckle with a broad-spectrum of antibacterial activity, suppressing tumor growth and other pharmacological effects. However, it is susceptible to damage during traditional extraction and separation processes. Therefore, developing selective and efficient extraction methods of CGA is essential. Based on computational molecular simulations, a reliable and efficient molecularly imprinted polymers (MIPs) were successfully developed for selective extraction of CGA. MIPs and non-molecularly imprinted polymers (NIPs) were synthesized using a precipitation polymerization method, employing three different functional monomers: [methacrylic acid (MAA), 4-vinylpyridine (4-VP), and methyl methacrylate (MMA)], with CGA serving as the template molecule. To simulate the polymers and predict the optimal ratio between the template and functional monomer, the computational studies and adsorption performance experiments were carried out. The adsorption characteristics and thermal stability of polymers were evaluated by isothermal adsorption, adsorption kinetics, selective adsorption and thermogravimetric analysis, aiming to obtain the MIPs with specific recognition and selectivity for CGA. When the molar ratio of template CGA to functional monomer 4-VP was 1:8, the prepared MIPs was found to have the maximum adsorption capacity (14.85 mg g−1) and the highest imprinting factor (1.74) at the CGA concentration of 100 mg L−1. These results were consistent with those obtained by computational molecular simulation. This study not only provides good guidance for developing separation materials for extracting CGA from natural plants but also inspires the application of computer simulation and molecular docking techniques in the preparation of specific MIPs materials. [ABSTRACT FROM AUTHOR]

Enzymes play crucial roles in life sciences, pharmaceuticals and industries as biological catalysts that speed up biochemical reactions in living organisms. New catalytic reactions are continuously developed by enzymatic engineering to meet industrial needs, which thereby drives the development of analytical approaches for real-time reaction monitoring to reveal catalytic processes. Here, taking the hydrolase— chymotrypsin as a model system, we proposed a convenient method for monitoring catalytic processes through native top-down mass spectrometry (native TDMS). The chymotrypsin sample heterogeneity was first explored. By altering sample introduction modes and pHs, covalent and noncovalent enzymatic complexes, substrates and products can be monitored during the catalysis and further confirmed by tandem MS. Our results demonstrated that native TDMS based catalysis monitoring has distinctive strength on real-time inspection and continuous observation, making it a promising tool for characterizing more biocatalysts. [Display omitted] • Heterogeneity and auto-catalyzing properties of chymotrypsin were identified by native TDMS. • Rapid catalysis was observed through theta emitter-based native TDMS. • Acyl-enzyme intermediate and non-covalent complexes were monitored during catalytic process. [ABSTRACT FROM AUTHOR]

This article explores the bioinspired total syntheses of gymnothelignans, which are natural products found in Gymnotheca chinensis plants. These gymnothelignans have unique structures and show moderate cytotoxic activities against cancer cells. The article presents two proposed pathways for their synthesis and discusses the total syntheses of eupodienone-type gymnothelignans. It also provides insights into their biogenetic relationships through chemical synthesis. The authors hope to initiate further discussions on this topic and provide information about their research interests. [Extracted from the article]

• A smartphone-assisted fluorescence-colorimetric immunosensing platform was proposed. • NH 2 -UiO-66@PtNPs was exploited to construct a fluorescence-colorimetric signal probe. • The multi-mode immunosensing microarray showed satisfactory results of AMD detection. • The efficient, visual and portable method showed great potential in food analysis. Amantadine (AMD) is an antiviral drug used to treat animal-based infectious diseases such as avian influenza. However, its illegal use in animal-derived food industries endangers human health. Therefore, an efficient, portable, and visual sensor to detect AMD in food is crucial for ensuring food safety. A multifunctional nanocomposite NH 2 -UiO-66@PtNPs was exploited to design a smartphone-assisted fluorescence-colorimetric immunosensing microarray for multidimensional detection of AMD in animal-derived foods. Platinum nanoparticles (NPs) were immobilized on a Zr-based metal–organic framework (NH 2 -UiO-66). Pt NPs exhibited peroxidase-like activity, whereas NH 2 -UiO-66 stabilized Pt NPs and improved the colorimetric signal of the sensor. Moreover, the fluorescence ligand NH 2 -BDC in NH 2 -UiO-66 was released via alkaline hydrolysis, amplifying the fluorescence signal and improving detection sensitivity. The smartphone-assisted color recognition system accurately identified the color changes of the microarray. The immunocompetitive reaction of AMD and the antibody (Ab) in the microarray NH 2 -UiO-66@PtNPs@Ab 2 allowed the quantitative and visual detection of AMD in a wide concentration range (0.1–1000 ng/mL) with high sensitivity [limit of detection = 0.0022 ng/mL (fluorescence), 0.069 ng/mL (colorimetric), and 0.68 ng/mL (smartphone)]. This detection strategy was verified in AMD-spiked food samples with satisfactory recoveries (82.0–103.0%) and stability (RSD: ≤7.1%, n = 3), showing its great potential for visual screening and portable detection of other food contaminants. [ABSTRACT FROM AUTHOR]

Ensuring food safety continues to be one of the major global challenges. For effective food safety monitoring, fast, sensitive, portable, and efficient food safety detection strategies must be devised. Metal organic frameworks (MOFs) are porous crystalline materials that have attracted attention for use in high-performance sensors for food safety detection owing to their advantages such as high porosity, large specific surface area, adjustable structure, and easy surface functional modification. Immunoassay strategies based on antigen–antibody specific binding are one of the important means for accurate and rapid detection of trace contaminants in food. Emerging MOFs and their composites with excellent properties are being synthesized, providing new ideas for immunoassays. This article summarizes the synthesis strategies of MOFs and MOF-based composites and their applications in the immunoassays of food contaminants. The challenges and prospects of the preparation and immunoassay applications of MOF-based composites are also presented. The findings of this study will contribute to the development and application of novel MOF-based composites with excellent properties and provide insights into advanced and efficient strategies for developing immunoassays. [Display omitted] • Emerging MOF-based composites for immunosensors in food safety were introduced. • The synthesis methods of emerging MOF-based composites were reviewed in detail. • The immunosensing applications of MOF-based composites were summarized. [ABSTRACT FROM AUTHOR]

Certain transmembrane α-helices of multi-pass membrane proteins line substrate transport paths or catalytic pockets and, therefore, are partially hydrophilic. Sec61 alone is insufficient to insert these less hydrophobic segments into the membrane and needs to work with dedicated membrane chaperones. Three such membrane chaperones have been described in the literature—the endoplasmic reticulum membrane protein complex (EMC), the TMCO1 complex, and the PAT complex. Recent structural studies on these membrane chaperones have revealed their overall architecture, multi-subunit assembly, putative substrate transmembrane helix-binding pockets, and cooperative mechanisms with the ribosome and Sec61 translocon. These structures are providing initial insights into the poorly understood processes of multi-pass membrane protein biogenesis. [ABSTRACT FROM AUTHOR]

Progress in structural biology research has led to a high demand for powerful and yet complementary analytical tools for structural characterization of proteins and protein complexes. This demand has significantly increased interest in native mass spectrometry (nMS), particularly native top‐down mass spectrometry (nTDMS) in the past decade. This review highlights recent advances in nTDMS for structural research of biological assemblies, with a particular focus on the extra multi‐layers of information enabled by TDMS. We include a short introduction of sample preparation and ionization to nMS, tandem fragmentation techniques as well as mass analyzers and software/analysis pipelines used for nTDMS. We highlight unique structural information offered by nTDMS and examples of its broad range of applications in proteins, protein‐ligand interactions (metal, cofactor/drug, DNA/RNA, and protein), therapeutic antibodies and antigen‐antibody complexes, membrane proteins, macromolecular machineries (ribosome, nucleosome, proteosome, and viruses), to endogenous protein complexes. The challenges, potential, along with perspectives of nTDMS methods for the analysis of proteins and protein assemblies in recombinant and biological samples are discussed. [ABSTRACT FROM AUTHOR]

The uplift mechanism and geodynamic model of the northeastern (NE) Tibetan Plateau remain controversial. Two competing models have been proposed for the uplift of the NE Tibetan Plateau, including crustal shortening through folding or thrust faulting and the middle-lower crustal flow model. Here, we applied the joint inversion of surface wave dispersions and receiver functions with P-wave velocity constraints on a dense linear broadband seismic array to obtain the Vs and Vp/Vs profiles of the crust and uppermost mantle across northeastern Tibet. The inversion yields robust structural images that show stark Vs and Vp/Vs jumps across the West Qinling fault from the Songpan-Ganzi and Kunlun-West Qinling terranes (south) to the Qilian and North China terranes (north). The results reveal that regional low-Vs/high-Vp/Vs anomalies present in the middle-to-lower crust, which may be the signature of viscous flow, are distinctly limited south of the West Qinling fault. In contrast, the imaged physical properties of the crust and mantle lithosphere north of this fault manifest a rigid pattern, which is inferred to be originated from the North China craton underthrust below the northern margin of the Tibetan plateau. Our seismic imaging indicates that the NE corner of the Tibetan Plateau does not currently serve as the flow channel of the ductile material from the central and northern Tibet. • Joint inversion produces crustal Vs and Vp/Vs structures across NE Tibet. • Revealing a distinct lithospheric property contrast across the West Qinling fault. • North of the West Qinling fault is manifested as a rigid pattern. • Inferred crustal flow is limited south of the West Qinling fault. [ABSTRACT FROM AUTHOR]

A variety of Bi3+ and/or Eu3+ doped KBaYSi 2 O 7 phosphors with deep blue, cyan, orange-red, and white light multicolor emissions have been fabricated by a Pechini sol-gel (PSG) method. The KBaYSi 2 O 7 :Bi3+ phosphors exhibit an intense cyan emission or a unique narrow deep blue emission when excited by different wavelengths, which may bridge the cyan gap or act as a promising deep blue phosphor for white light-emitting diodes (WLEDs). The tunable multicolor emissions can be achieved by changing the Bi3+ doping concentrations. The Bi3+/Eu3+ co-doped KBaYSi 2 O 7 phosphors display intrinsic emissions of Bi3+ and Eu3+ and an energy transfer process between Bi3+ and Eu3+ can be detected. The luminescence colors of KBaYSi 2 O 7 :Bi3+,Eu3+ regularly shift from blue, through cold and warm white, finally toward orange-red by adjusting the relative doping concentrations of Bi3+ and Eu3+. The single-phase white light-emitting material can be generated in both cold and warm white regions by simply varying the Eu3+ doping concentrations. Furthermore, three kinds of WLEDs devices are fabricated by KBaYSi 2 O 7 :Bi3+ or KBaYSi 2 O 7 :Bi3+,Eu3+ phosphors, which can exhibit dazzling white light emissions with eminent CIE coordinates, correlated color temperature, and color rendering index. The result offers direct evidence that the as-synthesized phosphors may be potentially applied in WLEDs and solid-state lighting. [ABSTRACT FROM AUTHOR]

[Display omitted] • A conceptual model of pulsed stirred electrodialytic extraction was presented. • Multivariate statistical analysis is used to illustrate the similarity of stirring systems. • Energy efficiency was improved by applying the pulsed stirring. Recycling valuable elements from municipal solid waste incineration fly ash and air pollution control (APC) residue has become the focus of research to manage this kind of residual waste. This paper assesses the possibility of energy savings to increase the economic sustainability of the electrodialytic (ED) recovery process by using pulsed stirring during extraction of As, Cd, Cr, Cu, Pb, and Zn from fly ash and APC residue suspensions and analyzing the data with multivariate statistical methods. Fly ash and APC residue in different batches were ED treated using different stirring frequencies of the ash suspensions, i.e., manually, 25%, 50%, 75%, and 100% (constant) stirring. An automatic camera was used to record the effect of pulsed stirring on the distribution of the ash suspensions during ED treatment and revealed three stages of the ash suspension during ED treatment that was presented in a conceptual model. The results showed that applying both pulsed and constant stirring could increase the acidification, the redox potential of ash suspensions, and the contact between ash particles and H+, thus boosting the extraction of metals. The regression coefficients and variable influence on projection values based on partial least squares models show similarity between 50% stirring and 100% stirring, indicating that it is possible to save energy by applying the stirrer only 50% of the time for all ashes, without compromising the extraction of the metals. [ABSTRACT FROM AUTHOR]

• The hydrogen bond interactions are crucial to small molecules binding to ApisOBP3. • Rational design strategy was used based on the binding cavity feature of ApisOBP3. • A novel acylpiperidine scaffold was firstly found to be aphid-repellent activity. Odorant-binding protein (OBP) is a promising potential target and can be used as a template for developing insect control agents due to its ability to bind to and transport semiochemicals to olfactory receptors, thus triggering behavioural responses among insects. In this study, 27 novel acylpiperidine analogues were designed and synthesised by introducing the hydrophobic long chain of the aphid alarm pheromone (E)-β-farnesene (EβF) into the polar acylpiperidine group of the commercial insect repellent icaridine based on the binding cavity characteristics of an OBP of the pea aphid Acyrthosiphon pisum , ApisOBP3. Compound 14c displayed good repellent activity against the pea aphids with a repellence rate of 61.5% at a concentration of 6 μg/μL. The equilibrium dissociation constant (K i) of compound 14c against ApisOBP3 was 20.92 μM in competitive fluorescence binding assays; this value is similar to the K i of the commercial insect repellent icaridine (20.56 μM). Molecular dynamics simulation revealed that the EβF long chain of compound 14c showed considerable hydrophobic interactions with the binding domain of ApisOBP3. Moreover, the acylpiperidine moiety of compound 14c formed one hydrogen bond and multiple carbon–hydrogen bonds with the Phe2 and Asn109 residues, respectively. The binding free energy analysis indicated that the contribution of the van der Waals force to the binding affinity was approximately twice as great as that of the electrostatic force. These studies provide significant guidance for the rational designing and efficient identification of novel insect repellent agents. [ABSTRACT FROM AUTHOR]

Despite the importance of early diagnosis and intervention, the diagnosis of autism spectrum disorders (ASDs) remains delayed as it is mostly based on clinical symptoms and abnormal behaviours appearing after 2 years of age. Identification of autistic markers remains a top priority in achieving an early and effective ASD diagnosis. We have previously reported that prenatal exposure of hormones or diabetes triggers epigenetic changes and oxidative stress, resulting in gene suppression with autism‐like behaviours in offspring. Here, a potential biomarker for ASD diagnosis was established through gene analysis in peripheral blood mononuclear cells (PBMCs). The study from in vivo mouse showed that prenatal hormone exposure or maternal diabetes suppresses mRNA expression of estrogen‐related receptor α (ERRα), superoxide dismutase 2 (SOD2), G protein‐coupled estrogen receptor (GPER) and retinoic acid‐related orphan receptor α (RORA) in the brain as well as oxidative stress and mitochondrial dysfunction, subsequently triggering autism‐like behaviour in mouse offspring. Also, similar gene suppression was found in hematopoietic stem cells (HSCs) and PBMC, with inherited epigenetic changes being identified on the related promoters. The human case–control study found that mRNA levels of ERRα, SOD2, GPER and RORA were significantly reduced in PBMC from ASD subjects (n = 132) compared with typically developing (n = 135) group. The receiver operating characteristic curve showed a.869 ±.021 of area under the curve for ASD subjects with 95% confidence interval of.829–.909, together with 1.000 of sensitivity and.856 of specificity. In conclusion, the combined mRNA expression in PBMC based on prenatal factor exposure‐mediated gene suppression could be a potential biomarker for ASD diagnosis. [ABSTRACT FROM AUTHOR]

Structural remodeling plays an important role in the occurrence and maintenance of atrial fibrillation (AF), but the mechanism is currently unclear. This study was designed to investigate the transcriptomic mechanism of structural remodeling of AF through bioinformatic analysis and in vivo and vitro experiments. Transcriptomic datasets were retrieved from the Gene Expression Omnibus (GEO) database, and bioinformatics analysis was performed to screen mRNAs associated with AF. Cell and animal models were constructed to verify the bioinformatic findings using RT-qPCR and western blot analysis. Then, SPP1 was screened as the target gene, and the mechanism by which it promotes fibrosis was further studied in human cardiac fibroblasts (HCFs) using western blot analysis. After retrieval, the GSE14975, GSE31821, GSE79768, GSE115574 and GSE128188 datasets were used in this study. In total, 147 differentially expressed genes (DEGs) were identified in left atrial appendix tissue and 85 in right atrial appendix tissue. According to the enrichment analysis results, the calcium signaling pathway was found to play an important role in AF, in which EGFR, AGTR1, HTR2B, CD38 and BDKRB1 might be the key genes. Moreover, SPP1 was identified as a key driver through PPI analysis and experimentally proved to reduce the expression of p27 by regulating the PI3K/Akt signaling pathway, sequentially promoting HCF fibrosis. Bioinformatics analysis showed that the calcium signaling pathway might play an important role in AF, while SPP1 could promote myocardial fibrosis through the PI3K/Akt/p27 signaling axis. [ABSTRACT FROM AUTHOR]

Restoring hexavalent chromium (Cr(VI)) to trivalent chromium (Cr(III)) from contaminated soil is a cost-effective alternative for attenuating Cr(VI) toxicity to the ecosystem. A new electrokinetic remediation (EKR) system with UV light was explored to overcome an energy barrier to catalyze Cr(VI) reduction from the surface soil near the anodic reservoir. Natural organic matters and minerals from the contaminated soil acted as electron donors and catalysts for Cr(VI) photo-reduction and no additional chemical reagent. There was almost no residual Cr(VI) in anolyte after UV/EKR compared with the conventional EKR. The reduction improved the efficiency of EKR in the soil near the anodic reservoir by dropped the Cr(VI) negative mass flux caused by electroosmosis advection and concentration diffusion. The pathways of Cr(VI) photo-reduction are possibly dominated by ligand-to-metal charge transfer, i.e., photocatalytic cyclic reduction by Fe(III)/Fe(II) complexes on the surface of the minerals and in soil pore fluid and the photo-induced decomposition of chromate ester. It is concluded that UV/EKR is a clean, efficient, and low-cost method for remediation of Cr(VI)-contaminated soil. [Display omitted] • Natural components of contaminated soil were utilized for Cr(VI) photoreduction. • UV treatment alleviated the Cr(VI) negative flux from the anolyte to the soil. • DC electric field favored Cr(VI) photoreduction through driving force and protons. • Cr(VI) in the soil after EKR was studied by the two-step sequential extraction method. [ABSTRACT FROM AUTHOR]

The activation of pregnane X receptor (PXR) or peroxisome proliferator-activated receptor α (PPARα) can induce liver enlargement. Recently, we reported that PXR or PPARα activation-induced hepatomegaly depends on yes-associated protein (YAP) signaling and is characterized by hepatocyte hypertrophy around the central vein area and hepatocyte proliferation around the portal vein area. However, it remains unclear whether PXR or PPARα activation-induced hepatomegaly can be reversed after the withdrawal of their agonists. In this study, we investigated the regression of enlarged liver to normal size following the withdrawal of PCN or WY-14643 (typical agonists of mouse PXR or PPARα) in C57BL/6 mice. The immunohistochemistry analysis of CTNNB1 and KI67 showed a reversal of hepatocyte size and a decrease in hepatocyte proliferation after the withdrawal of agonists. In details, the expression of PXR or PPARα downstream proteins (CYP3A11, CYP2B10, ACOX1, and CYP4A) and the expression of proliferation-related proteins (CCNA1, CCND1, and PCNA) returned to the normal levels. Furthermore, YAP and its downstream proteins (CTGF, CYR61, and ANKRD1) also restored to the normal states, which was consistent with the change in liver size. These findings demonstrate the reversibility of PXR or PPARα activation-induced hepatomegaly and provide new data for the safety of PXR and PPARα as drug targets. • PXR or PPARα activation-induced hepatomegaly is reversible. • The hepatocyte size and proliferation return to normal state after the reversal. • Protein levels altered by PXR or PPARα activation are restored after the reversal. [ABSTRACT FROM AUTHOR]

Human pluripotent stem cell (hPSC)-derived red blood cells (RBCs) possess great potential for compensating shortages in transfusion medicine. For better RBC generation from hPSCs, we compared the cell seeding density in the embryoid body formation-based hPSC induction protocol. In the selection of low- and high-density inoculation conditions, we found that low-density culture performed better in the final RBC product with more cell output and increased average cellular hemoglobin content. An elaborate study using flow cytometry demonstrated that low inoculation density promoted endothelial-to-hematopoietic transition, followed by improved hematopoietic progenitor formation and erythrocyte generation. The improved transformation from glycolysis to mitochondrial oxidation and reduced apoptosis might be responsible for this effect. Hints from RNA sequencing suggested that molecules involved in microenvironment interaction and metabolic regulation might respond for the different developmental potential. The possible mediators between outer message and intracellular response could be the nutrition sensors FOXO, PRKAA1 (AMPK), and MTOR genes. It is possible that low inoculation density triggered metabolic regulation signals, promoted mitochondrial oxidation, and resulted in enhanced cell amplification and hematopoietic differentiation. The low cell culture density will improve RBC generation from hPSCs. [ABSTRACT FROM AUTHOR]

The first total synthesis of the Euphorbia diterpenoid pepluacetal is disclosed in both racemic and chiral fashions. The synthesis strategically relies on a photo‐induced Wolff rearrangement/lactonization cascade (WRLC) reaction to access the cyclobutane moiety, a ring‐closing metathesis/cyclopropanation sequence to rapidly forge the 7–3 bicyclic system, and a late‐stage Rh‐catalyzed transannular carbenoid insertion to C(sp3)−H bond followed by a Baeyer–Villiger oxidation and ring‐opening manipulations to install the side chain. The synthetic route demonstrates excellent stereochemical control on the non‐classical concave‐face bond formation, remote traceless stereochemical relay and high scalability to provide 20 mg of (+)‐pepluacetal. [ABSTRACT FROM AUTHOR]

The first total synthesis of the Euphorbia diterpenoid pepluacetal is disclosed in both racemic and chiral fashions. The synthesis strategically relies on a photo‐induced Wolff rearrangement/lactonization cascade (WRLC) reaction to access the cyclobutane moiety, a ring‐closing metathesis/cyclopropanation sequence to rapidly forge the 7–3 bicyclic system, and a late‐stage Rh‐catalyzed transannular carbenoid insertion to C(sp3)−H bond followed by a Baeyer–Villiger oxidation and ring‐opening manipulations to install the side chain. The synthetic route demonstrates excellent stereochemical control on the non‐classical concave‐face bond formation, remote traceless stereochemical relay and high scalability to provide 20 mg of (+)‐pepluacetal. [ABSTRACT FROM AUTHOR]

Previous studies have shown that vibration- or rotation-based techniques can effectively mitigate the fouling and concentration polarization during membrane filtration. However, it is difficult to incorporate these active enhancement techniques with spiral wound modules (SWMs), which are widely employed in drinking water and wastewater treatment. In this work a prototype membrane system was developed to accommodate angular vibrations with a modified SWM. With this prototype system, a series of filtration experiments were designed and implemented to investigate the effect of angular vibrations on the ultrafiltration algal fouling process in an SWM. The experimental results indicate that the algal fouling in an SWM can be effectively controlled (up to ∼28.5 % at 15 Hz) by applying angular vibrations in conjunction with appropriate operating conditions; the underlying mechanisms are discussed using a mathematical model that accounts for the relative motion between the fluid and membrane when they are subject to external accelerations, related to the vibration frequency, filtration period and position along coiled membrane leaves. A quantitative analysis is also presented to demonstrate the potential of using angular oscillations to control the algal fouling in an SWM with a lower energy consumption compared to the conventional method of increasing the cross-flow rate. [Display omitted] • An angular vibrating spiral wound membrane system is developed in a lab scale. • Angular vibration effects on the cell trajectory and flow velocity were simulated. • EOM could enhance the angular vibration effect via promoting algal cell aggregation. • Increasing crossflow rate may weaken the fouling control efficiency by this vibration. • Power for fouling control by the vibration was less than that by increasing crossflow. [ABSTRACT FROM AUTHOR]

During bacterial cell growth, hydrolases cleave peptide cross-links between strands of the peptidoglycan sacculus to allow new strand insertion. The Pseudomonas aeruginosa carboxyl-terminal processing protease (CTP) CtpA regulates some of these hydrolases by degrading them. CtpA assembles as an inactive hexamer composed of a trimer-of-dimers, but its lipoprotein binding partner LbcA activates CtpA by an unknown mechanism. Here, we report the cryo-EM structures of the CtpA–LbcA complex. LbcA has an N-terminal adaptor domain that binds to CtpA, and a C-terminal superhelical tetratricopeptide repeat domain. One LbcA molecule attaches to each of the three vertices of a CtpA hexamer. LbcA triggers relocation of the CtpA PDZ domain, remodeling of the substrate binding pocket, and realignment of the catalytic residues. Surprisingly, only one CtpA molecule in a CtpA dimer is activated upon LbcA binding. Also, a long loop from one CtpA dimer inserts into a neighboring dimer to facilitate the proteolytic activity. This work has revealed an activation mechanism for a bacterial CTP that is strikingly different from other CTPs that have been characterized structurally. Synopsis: The Pseudomonas aeruginosa cell envelope protease CtpA is activated by the LbcA lipoprotein to degrade cell-wall cross-link hydrolases. Here, structural, biochemical and in vivo approaches show how this activation occurs, revealing a unique mechanism compared to related proteases. CtpA alone is inactive and exists mainly as a dimer at physiological temperature. After LbcA binds to a CtpA dimer, the LbcA-CtpA complex oligomerizes into a CtpA hexamer with three bound LbcA proteins. Only one CtpA molecule is activated within each CtpA dimeric unit. The binding of LbcA triggers a series of conformational changes in the activated CtpA, including a shift of the PDZ domain, realignment of the catalytic site, and remodeling of substrate binding pocket. Structural, biochemical and in vivo approaches reveal a unique mechanism for cell envelope CtpA protease activation by its lipoprotein binding partner LbcA. [ABSTRACT FROM AUTHOR]

To study the impact of cutting blasting on the surface, a vibration waveform prediction function was constructed, and a method of dividing the affected area was proposed. Based on the equivalent spherical charge theory, it is possible to establish a connection between the fitting coefficient and the engineering parameters in the equivalent source intensity function. Furthermore, a blasting vibration waveform function suitable for engineering can be constructed. Secondly, the reliability of the method introduced is verified through the data monitored on-site. Finally, the affected partitions of blasting vibration are divided based on the peak particle velocity and vibration displacement as standards. The results show that the vibration waveform prediction system introduced can restore the vibration waveform corresponding to cutting blasting. In addition, the zoning method can reasonably divide the scope of the affected area. [ABSTRACT FROM AUTHOR]

Objectives: To test the feasibility, acceptability, and potential efficacy of a mHealth intervention tailored for Chinese immigrant families with type 2 diabetes (T2D). Methods: We conducted a pilot randomized controlled trial (RCT) with baseline, 3-, and 6-month measurements. Participating dyads, T2D patients and families/friends from NYC, were randomized into the intervention group (n = 11) or the wait-list control group (n = 12). Intervention includes 24 videos covering T2D self-management, behavioral techniques, and family-oriented sessions. Feasibility and acceptability were measured respectively by the retention rate and video watch rate, and a satisfaction survey. Patients' HbA1c, weight, and self-management were also assessed to test potential efficacy. Results: Most T2D patients (n = 23; mean age 56.2±9.4 years; 52.2% male) and families/friends (n = 23, mean age 54.6±11.2 years; 52.2% female) had high school education or less (69.6% and 69.6%), annual household income < $25,000 (65.2% and 52.2%), and limited English proficiency (95.7% and 95.7%). The retention rates were not significantly different between the intervention and the control groups for both the patients (90.91% vs 83.3%, p = 0.589); and their families/friends (3-month: 90.9% vs 75%, p = 0.313; 6-month: 90.9% vs 83.3%, p = 0.589). The mean video watch rate was 76.8% (7%). T2D patients and families/friends rated satisfaction as 9.4 and 10 out of 10, respectively. Despite no between-group differences, the intervention group had significantly lower HbA1c (p = 0.014) and better self-management (p = 0.009), and lost 12 lbs. on average at 6 months (p = 0.079), compared to their baseline levels. Conclusions: A culturally-tailored, family-based mHealth intervention is feasible and acceptable among low-income, limited English-proficient Chinese families with T2D in NYC. Significant changes in HbA1c and self-management within the intervention group indicate this intervention may have potential efficacy. Given the small sample size of this study, a future RCT with adequate power is needed to test efficacy. [ABSTRACT FROM AUTHOR]

Halide perovskite is an emerging material with excellent optoelectronic properties, and also widely used in neuromorphic devices. Recently, halide perovskite has been redefined as exhibiting extraordinary multifunction, e.g., photoferroelectricity. Herein, this work employs a composite material consisting of halide perovskite and organic ferroelectric material to develop a new photoferroelectric synapse, and the photoferroelectricity and some synaptic plasticity are investigated. By the corresponding test analysis, it is demonstrated that photoelectricity and ferroelectricity can reinforce each other in this photoferroelectric composite material. Versatile synaptic behaviors of the nervous system, including paired‐pulse facilitation/paired‐pulse depression, post‐tetanic potentiation /post‐tetanic depression, and spiking‐rate‐dependent plasticity, are successfully simulated. Particularly, the classical conditioning in Pavlov's dog experiment can be replicated in the photoferroelectric synapse to realize the learning function of the brain, including memory loss and recovery. This work could be conducive to the application of multifunctional perovskite materials in synapse devices and neuromorphic computing. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common neurodegenerative disease worldwide and has a high incidence in the elderly. Unfortunately, there is no effective therapy for AD owing to its complicated pathogenesis. However, the development of lipid-lowering anti-inflammatory drugs has heralded a new era in the treatment of Alzheimer's disease. Several studies in recent years have shown that lipid metabolic dysregulation and neuroinflammation are associated with the pathogenesis of AD. 3-Hydroxyl 3-methylglutaryl CoA reductase (HMGCR) is a rate-limiting enzyme in cholesterol synthesis that plays a key role in cholesterol metabolism. HMGCR inhibitors, known as statins, have changed from being solely lipid-lowering agents to neuroprotective compounds because of their effects on lipid levels and inflammation. In this review, we first summarize the main regulatory mechanism of HMGCR affecting cholesterol biosynthesis. We also discuss the pathogenesis of AD induced by HMGCR, including disordered lipid metabolism, oxidative stress, inflammation, microglial proliferation, and amyloid-β (Aβ) deposition. Subsequently, we explain the possibility of HMGCR as a potential target for AD treatment. Statins-based AD treatment is an ascent field and currently quite controversial; therefore, we also elaborate on the current application prospects and limitations of statins in AD treatment. [ABSTRACT FROM AUTHOR]

We employ two‐dimensional (2D) α-In2Se3 nanosheets and polymethyl methacrylate (PMMA) materials to develop three types of devices with different resistive switching (RS) layer structures and deeply study the electrical properties and physical mechanisms of these devices. It is confirmed that the pure 2D α-In2Se3 nanosheet-based RS device is a mode of ferroelectric regulation of the potential barrier, exhibiting memristor characteristics that can mimic the synaptic plasticity. Meanwhile, PMMA can improve the RS properties of the α-In2Se3 nanosheet-based device, including the appropriate switching ratio, narrow ratio distribution, and good endurance and retention capability, but the device's physical mechanism changes to charge trapping assisted hopping mechanism from the ferroelectric regulation of the potential barrier. [ABSTRACT FROM AUTHOR]