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[Display omitted] Lithium cobalt phosphate (LiCoPO 4) has great potential to be developed as a cathode material for lithium-ion batteries (LIBs) due to its structural stability and higher voltage platform with a high theoretical energy density. However, the relatively low diffusion of lithium ions still needs to be improved. In this work, Fe and Zn co-doped LiCoPO 4 : LiCo 0.9-x Fe 0.1 Zn x PO 4 /C is utilized to enhance the battery performance of LiCoPO 4. The electrochemical properties of LiCo 0.85 Fe 0.1 Zn 0.05 PO 4 /C demonstrated an initial capacity of 118 mAh/g, with 93.4 % capacity retention at 1C after 100 cycles, and a good capacity of 87 mAh/g remained under a high current density of 10C. In addition, the diffusion rate of Li ions was investigated, proving the improvement of the materials with doping. The impedance results also showed a smaller resistance of the doped materials. Furthermore, operando X-ray diffraction displayed a good reversibility of the structural transformation, corresponding to cycling stability. This work provided studies of both the electrochemical properties and structural transformation of Fe and Zn co-doped LiCoPO 4 , which showed that 10 % Fe and 5 % Zn co-doping enhanced the electrochemical performance of LiCoPO 4 as a cathode material in LIBs. [ABSTRACT FROM AUTHOR]

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]

With the development and popularity of intelligent store terminals, contactless distribution has been a hot talk on medical supplies using intelligent express boxes. Based on the traditional vehicle routing problem, this paper considers the sharing economy and open-loop distribution reality hotspots and considers the optimization of carbon emissions in contactless distribution. The travel distance and load capacity are the key factors affecting carbon emissions. The carbon emission model proposes dual goals of minimizing distribution costs and carbon emissions. It constructs a distribution path planning model with multiple distribution stations. To solve this problem with multidepot optimization, we design a hybrid genetic algorithm, and according to the strategy of customer distance clustering analysis, the dispatching of vehicles is divided into three steps. The principle of elite crossing is applied to avoid the solution to fall into local optimum. The experimental results show that the proposed model and optimization algorithm can get a tradeoff between the logistics cost and carbon emissions. [ABSTRACT FROM AUTHOR]

• The GT-C glycosyltransferases are membrane-associated enzyme complexes that use dolichol-linked donor substrates. • Eukaryotic OST complexes mediate protein N -glycosylation. • The yeast Pmt1–Pmt2 complex catalyzes protein O -mannosylation. • The yeast Alg6 is involved in the synthesis of oligosaccharide donor substrates for OST. • The glycosyltransferases EmbA-C and AftD are involved in mycobacterial cell-wall synthesis. The structural folds of glycosyltransferases are categorized into three superfamilies: GT-A, GT-B, and GT-C. Few structures of GT-C fold existed in the Protein Data Bank prior to the recent advent of high-resolution cryo-EM, because the glycosyltransferases are large membrane proteins that are difficult to crystallize. The use of cryo-EM has resulted in the structures of several key GT-C glycosyltransferases. Here we summarize the latest structural features of and mechanistic insights into these membrane enzyme complexes. [ABSTRACT FROM AUTHOR]

Diquinane or bicyclo[3.3.0]octane is a conspicuous structural unit existing in the carbo‐frameworks of a wide range of natural products such as alkaloids and terpenoids. These diquinane‐containing molecules not merely exhibit intriguing architectures, but also showcase a broad spectrum of significant bioactivities, which draw widespread attention from the global synthetic community. During the past decade, with an aim to accomplish the total syntheses of such specified cornucopias of natural products, a variety of elegant strategies for construction of the diquinane ring system have been disclosed. In this Minireview, the achievements on this subject in the timeline from 2010 to June 2020 are demonstrated and it is discussed how the diquinane unit is strategically forged in the context of the specific target structure. In addition, impacts of the selected works to the field of natural product total synthesis is highlighted and the particular outlook of diquinane‐containing natural product synthesis is provided. [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]

An Ru‐doping strategy is reported to substantially improve both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) electrocatalytic activity of Ni/Fe‐based metal–organic framework (MOF) for overall water splitting. As‐synthesized Ru‐doped Ni/Fe MIL‐53 MOF nanosheets grown on nickel foam (MIL‐53(Ru‐NiFe)@NF) afford HER and OER current density of 50 mA cm−2 at an overpotential of 62 and 210 mV, respectively, in alkaline solution with a nominal Ru loading of ≈110 μg cm−2. When using as both anodic and cathodic (pre‐)catalyst, MIL‐53(Ru‐NiFe)@NF enables overall water splitting at a current density of 50 mA cm−2 for a cell voltage of 1.6 V without iR compensation, which is much superior to state‐of‐the‐art RuO2‐Pt/C‐based electrolyzer. It is discovered that the Ru‐doping considerably modulates the growth of MOF to form thin nanosheets, and enhances the intrinsic HER electrocatalytic activity by accelerating the sluggish Volmer step and improving the intermediate oxygen adsorption for increased OER catalytic activity. [ABSTRACT FROM AUTHOR]

The replication of DNA in chromosomes is initiated at sequences called origins at which two replisome machines are assembled at replication forks that move in opposite directions. Interestingly, in vivo studies observe that the two replication forks remain fastened together, often referred to as a replication factory. Replication factories containing two replisomes are well documented in cellular studies of bacteria (Escherichia coli and Bacillus subtilis) and the eukaryote, Saccharomyces cerevisiae. This basic twin replisome factory architecture may also be preserved in higher eukaryotes. Despite many years of documenting the existence of replication factories, the molecular details of how the two replisome machines are tethered together has been completely unknown in any organism. Recent structural studies shed new light on the architecture of a eukaryote replisome factory, which brings with it a new twist on how a replication factory may function. [ABSTRACT FROM AUTHOR]

In order to help user terminal devices (UTDs) efficiently handle computation-intensive and time-delay sensitive computing task, multi-access edge computing (MEC) has been proposed. However, due to the differences among the performance of UTDs, and the resource limitation of MEC servers, the joint optimization between the offloading decisions of UTDs and the allocation of resources in network is still a focus of the research. This paper studies the joint computation offloading and resource allocation strategy in multi-user and multi-server scenarios. Firstly, we formulate the joint optimization problem of computation offloading and resource allocation as a mixed integer nonlinear programming (MINP) problem to minimize the energy consumption of UTDs, by constraining the offloading decision, channel selection, power allocation and resource allocation. Secondly, we propose a two-stage heuristic optimization algorithm based on genetic algorithms, which divides the joint optimization problem of computation offloading and resource allocation in two stages. Based on the coupling relationship between the offloading decision and the resource allocation scheme, we iteratively update the solution of the problem, and finally obtain the stable convergence solution of the optimization problem. Finally, the proposed algorithm is compared with other classical methods to prove the effectiveness. [ABSTRACT FROM AUTHOR]

This paper deals with the fixed-time tracking control problem of extended nonholonomic chained-form systems with state observers. According to the structure characteristic of such chained-form systems, two subsystems are considered to design controllers, respectively. First of all, using the fixed-time control theory, a controller is proposed to make the first tracking error subsystem converge to zero in bounded time independent initial state. Second, a state observer is proposed to estimate the unmeasurable states of the second subsystem. And the precise state estimation can be presented from the observer within finite time; moreover, the upper bound of time is a constant independent on the initial estimation error. Third, a fixed-time controller is designed to drive all states of the second chained-form subsystem to zero within pre-calculated time. Finally, the effectiveness of the proposed control scheme is validated by simulation results. [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]

Circadian clock and cell cycle are vital cellular programs acting in a timely-regulated, cyclic manner. The two cellular oscillators are coupled in various ways to facilitate biological processes. Here we report CDK9, a kinase belongs to the CDK family in regulating cell cycle and RNA Pol II activity, can serve as a modulator for circadian clock. We identified CDK inhibitor LY2857785 potently blocked PER2:LUC expression in MEFs from a screen of 17 commonly-used CDK inhibitors. We further analyzed the possible targets of LY2857785 by siRNA approach, and confirmed CDK9 as the main effector. LY2857785 treatment, as well as Cdk9 knock-down, led to lowered expression of Bmal1 in accordance with elevated expression of Rev-Erbα. CDK9 associated with REV-ERBα thus attenuated REV-ERBα binding to the RORE for Bmal1 suppression. To conform the circadian-modulating activity of CDK9 in vivo , we knocked down CDK9 in mice at the anterior hypothalamus covering the central oscillator SCN, and found the respiratory exchange ratio, daily activity and circadian period were altered in the Cdk9- knockdown mice. Together, our finding designated CDK9 as a novel modulator in circadian clock. CDK9 may serve as a vital basis to understand circadian- and cell cycle-misregulated ailments such as cancer. • CDKs inhibitor LY2857785 altered PER2 oscillation through CDK9. • CDK9 suppressed REV-ERBα levels and mitigated REV-ERBα binding to the Bmal1 RORE. • Knockdown Cdk9 at the SCN leads to circadian period change. [ABSTRACT FROM AUTHOR]

N‐glycosylation is one of the predominant modifications of eukaryotic proteins. It is catalyzed by oligosaccharyl transferase (OST), an eight‐subunit protein complex in the endoplasmic reticulum membrane. OST transfers the oligosaccharide from a lipid‐linked donor (LLO) to the Asn‐Xaa‐Ser/Thr sequon of nascent polypeptide, usually cotranslationally by partnering with the ribosome and the translocon. We and two other groups have recently determined high‐resolution cryo‐EM structures of the yeast and mammalian OST complexes. In this Structural Snapshot, we describe the molecular mechanism of eukaryotic OST and its interaction with the translocon. [ABSTRACT FROM AUTHOR]

Intelligent networks are regarded as existing networks incorporating some intelligent mechanisms such as cognitive and cooperative approaches to improve network performance. Security is highly essential in intelligent networks but has received less attention so far. In this article, we propose a framework that enables a secure intelligent network with the assistance of cloud-assisted privacy-preserving machine learning. In the framework, the cloud server can first generate a model using outsourced machine learning algorithms and then process testing data from the network with the generated model in real time, which reflects to the network and makes it more intelligent. At the same time, the proposal guarantees the security and privacy of both the training data and the testing data in the sense that the proposed framework takes advantage of differential privacy to perform privacy-preserving data analysis and homomorphic encryption to conduct valid operations over encrypted data. The performance evaluations of the core primitives employed in the framework including differential privacy and homomorphic encryption algorithms demonstrate the practicability of our proposal. [ABSTRACT FROM AUTHOR]

DEAD (Asp–Glu–Ala–Asp) box polypeptide 41 (DDX41), a receptor belonging to DExD/H-box helicase family, acts as an intracellular DNA sensor and induces type I IFN production in mammals and fish. However, the function of avian DDX41 in innate immune response is still unknown. In this study, the full-length duck DDX41 (duDDX41) cDNA sequence was cloned for the first time and encoded a putative protein of 618 amino acid residues which showed the high sequence similarity with both zebra finch and chicken DDX41s. The duDDX41 mRNA was widely distributed in all tested tissues, especially the cerebrum, cerebellum, and liver. Overexpression of duDDX41 triggered the activation of transcription factors IRF1 and NF-κB, as well as IFN-β expression in DEFs. The DEADc domain of duDDX41 played an extremely vital role in duck type I IFN signaling pathway. Knockdown of duDDX41 by siRNA silencing dramatically decreased IFN-β expression stimulated by poly(dA:dT) or duck enteritis virus (DEV). In addition, the replication of DEV was significantly inhibited in duDDX41-expressed DEFs and was enhanced in DDX41 knockdown DEFs. These results suggest that DDX41 is an important cytosolic DNA sensor and plays a crucial role in duck antiviral innate immune response. [ABSTRACT FROM AUTHOR]

Native mass spectra of large, polydisperse biomolecules with repeated subunits, such as lipoprotein Nanodiscs, can often be challenging to analyze by conventional methods. The presence of tens of closely spaced, overlapping peaks in these mass spectra can make charge state, total mass, or subunit mass determinations difficult to measure by traditional methods. Recently, we introduced a Fourier Transform-based algorithm that can be used to deconvolve highly congested mass spectra for polydisperse ion populations with repeated subunits and facilitate identification of the charge states, subunit mass, charge-state-specific, and total mass distributions present in the ion population. Here, we extend this method by investigating the advantages of using overtone peaks in the Fourier spectrum, particularly for mass spectra with low signal-to-noise and poor resolution. This method is illustrated for lipoprotein Nanodisc mass spectra acquired on three common platforms, including the first reported native mass spectrum of empty “large” Nanodiscs assembled with MSP1E3D1 and over 300 noncovalently associated lipids. It is shown that overtone peaks contain nearly identical stoichiometry and charge state information to fundamental peaks but can be significantly better resolved, resulting in more reliable reconstruction of charge-state-specific mass spectra and peak width characterization. We further demonstrate how these parameters can be used to improve results from Bayesian spectral fitting algorithms, such as UniDec.ᅟ [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]

The eukaryotic helicase is an 11‐subunit machine containing an Mcm2‐7 motor ring that encircles DNA, Cdc45 and the GINS tetramer, referred to as CMG ( Cdc45, Mcm2‐7, GINS). CMG is “built” on DNA at origins in two steps. First, two Mcm2‐7 rings are assembled around duplex DNA at origins in G1 phase, forming the Mcm2‐7 “double hexamer.” In a second step, in S phase Cdc45 and GINS are assembled onto each Mcm2‐7 ring, hence producing two CMGs that ultimately form two replication forks that travel in opposite directions. Here, we review recent findings about CMG structure and function. The CMG unwinds the parental duplex and is also the organizing center of the replisome: it binds DNA polymerases and other factors. EM studies reveal a 20‐subunit core replisome with the leading Pol ϵ and lagging Pol α‐primase on opposite faces of CMG, forming a fundamentally asymmetric architecture. Structural studies of CMG at a replication fork reveal unexpected details of how CMG engages the DNA fork. The structures of CMG and the Mcm2‐7 double hexamer on DNA suggest a completely unanticipated process for formation of bidirectional replication forks at origins. [ABSTRACT FROM AUTHOR]

Diabetic osteoporosis (DO) is a complication of diabetes. Zishen Jiangtang Pill (ZJP) is a Chinese herbal product which has been used in clinic to maintain blood glucose level and bone density for decades. However, the evidence about its mechanism on diabetes and osteoporosis is still unknown. The aim of this study is to investigate therapeutic effect of ZJP on DO in streptozotocin- (STZ-) induced rats. Rats were randomly assigned to 4 groups: one control group (CON), one model group (MOD), and two ZJP treatment groups (1.5 and 3.0 g/kg/d). All rats were treated for 8 weeks. Results showed that ZJP decreased the blood glucose level during OGTT and prevented the changes of FBG and Fins. Similarly, ZJP inhibited the changes of BCa, P, TRACP-5b, CTX-1, BALP, and BGP and the reduction of BMD. In parallel, 1H-NMR metabolomic studies showed that ZJP significantly altered the metabolic fingerprints of blood and urine level. These findings suggest that ZJP can effectively improve glucose metabolism, abnormal bone metabolism, and metabolic disorders in DO rats, which may be a useful alternative medicine for DO therapy. [ABSTRACT FROM AUTHOR]

Human LSm14A is a key component of processing body (P-body) assembly that mediates interferon-β (IFN-β) production by sensing viral RNA or DNA. To the best of our knowledge, we are the first to report duck LSm14A (duLSm14A) cloning from duck embryo fibroblasts (DEFs). Full-length duLSm14A encoded 461 amino acids and was highly homologous with chicken and swan goose sequences. More interestingly, the duLSm14A mRNA was extensively expressed in all the studied tissues. In DEFs, duLSm14A was localized in the cytoplasm as P-body-like dots. Expression of duLSm14A induced IFN-β through the activation of interferon regulatory factor-1 and nuclear factor-κB in DEFs. Furthermore, knockdown of duLSm14A by small interfering RNA notably decreased poly(I:C)- or duck reovirus-induced IFN-β production. The present study results indicate that the duLSm14A is an essential sensor that mediates duck innate immunity against viral infections. [ABSTRACT FROM AUTHOR]

Nucleotide-binding oligomerization domain 1 (NOD1) is an imperative cytoplasmic pattern recognition receptor (PRR) and considered as a key member of the NOD-like receptor (NLR) family which plays a critical role in innate immunity through sensing microbial components derived from bacterial peptidoglycan. In the current study, the full-length of duck NOD1 (duNOD1) cDNA from duck embryo fibroblasts (DEFs) was cloned. Multiple sequence alignment and phylogenetic analysis demonstrated that duNOD1 exhibited a strong evolutionary relationship with chicken and rock pigeon NOD1. Tissue-specific expression analysis showed that duNOD1 was widely distributed in various organs, with the highest expression observed in the liver. Furthermore, duNOD1 overexpression induced NF-κB activation in DEFs and the CARD domain is crucial for duNOD1-mediated NF-κB activation. In addition, silencing the duNOD1 decreased the activity of NF-κB in DEFs stimulated by iE-DAP. Overexpression of duNOD1 significantly increased the expression of TNF-α, IL-6, and RANTES in DEFs. These findings highlight the crucial role of duNOD1 as an intracellular sensor in duck innate immune system. [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 surgical robot, a costly technology for treatment of prostate cancer with equivocal marginal benefit, rapidly diffused into clinical practice. We sought to evaluate the role of teaching in the early adoption phase of the surgical robot. Teaching hospitals were the primary early adopters: data from the Healthcare Cost and Utilization Project showed that surgical robots were acquired by 45.5% of major teaching, 18.0% of minor teaching and 8.0% of non-teaching hospitals during the early adoption phase. However, teaching hospital faculty produced little comparative effectiveness research: By 2008, only 24 published studies compared robotic prostatectomy outcomes to those of conventional techniques. Just ten of these studies (41.7%) were more than minimally powered, and only six (25%) involved cross-institutional collaborations. In adopting the surgical robot, teaching hospitals fulfilled their mission to innovate, but failed to generate corresponding scientific evidence. [ABSTRACT FROM AUTHOR]

An efficient organocatalytic enantioselective aza-Piancatelli rearrangement is disclosed. The powerful process provides rapid access to valuable chiral 4-amino-2-cyclopentenone building blocks from readily available 2-furfurylcarbinols with excellent chemo-, enantio-, and diastereoselectivities under mild reaction conditions. [ABSTRACT FROM AUTHOR]