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The high-level organization of the cell is embedded in indirect relationships that connect distinct cellular processes. Existing computational approaches for detecting indirect relationships between genes typically consist of propagating abstract information through network representations of the cell. However, the selection of genes to serve as the source of propagation is inherently biased by prior knowledge. Here, we sought to derive an unbiased view of the high-level organization of the cell by identifying the genes that propagate and receive information most effectively in the cell, and the indirect relationships between these genes. To this aim, we adapted a perturbation-response scanning strategy initially developed for identifying allosteric interactions within proteins. We deployed this strategy onto an elastic network model of the yeast genetic interaction profile similarity network. This network revealed a superior propensity for information propagation relative to simulated networks with similar topology. Perturbation-response scanning identified the major distributors and receivers of information in the network, named effector and sensor genes, respectively. Effectors formed dense clusters centrally integrated into the network, whereas sensors formed loosely connected antenna-shaped clusters and contained genes with previously characterized involvement in signal transduction. We propose that indirect relationships between effector and sensor clusters represent major paths of information flow between distinct cellular processes. Genetic similarity networks for fission yeast and human displayed similarly strong propensities for information propagation and clusters of effector and sensor genes, suggesting that the global architecture enabling indirect relationships is evolutionarily conserved across species. Our results demonstrate that elastic network modeling of cellular networks constitutes a promising strategy to probe the high-level organization and cooperativity in the cell., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: A.-R.C. is a member of the scientific advisory board for Flagship Labs 69, Inc.

Family with sequence similarity 107, member A(FAM107A) was supposed as a tumor suppressor for various types of tumors. However, no pan-cancer analysis of FAM107A is available. Therefore, we conducted a FAM107A-related pan-cancer analysis across thirty-three tumors based on TCGA database to explore the molecular characteristics of FAM107A. The FAM107A expression is reduced in most cancers, and its down-regulated expression was linked to poor overall survival and progression-free survival of tumor patients. Analysis of DNA methylation of the FAM107A gene showed a negative correlation between FAM107A expression and promoter methylation in numerous cancers. Furthermore, FAM107A expression was noted to be involved in myeloid-derived suppressor cell infiltration in multiple cancers. To explore the mechanism of FAM107A in cancers, KEGG, and GO enrichment analysis was performed and the result showed "cell adhesion" and "cAMP signaling pathway" terms as the potential impact of FAM107A on cancers. An experiment in vitro showed FAM107A knockdown promoted the proliferation, migration, and invasion of bladder cancer and renal cancer cells. Our study indicates that FAM107A may be a putative tumor suppressor in bladder cancer and other tumors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ou, Zhang, Wu, Shen, Huang, She, She and Lin.)

In this report, we discovered a new entity named cataract, alopecia, oral mucosal disorder, and psoriasis-like (CAOP) syndrome in two unrelated and ethnically diverse patients. Furthermore, patient 1 failed to respond to regular treatment. We found that CAOP syndrome was caused by an autosomal recessive defect in the mitochondrial membrane-bound transcription factor peptidase/site-1 protease (MBTPS1, S1P). Mitochondrial abnormalities were observed in patient 1 with CAOP syndrome. Furthermore, we found that S1P is a novel mitochondrial protein that forms a trimeric complex with ETFA/ETFB. S1P enhances ETFA/ETFB flavination and maintains its stability. Patient S1P variants destabilize ETFA/ETFB, impair mitochondrial respiration, decrease fatty acid β-oxidation activity, and shift mitochondrial oxidative phosphorylation (OXPHOS) to glycolysis. Mitochondrial dysfunction and inflammatory lesions in patient 1 were significantly ameliorated by riboflavin supplementation, which restored the stability of ETFA/ETFB. Our study discovered that mutations in MBTPS1 resulted in a new entity of CAOP syndrome and elucidated the mechanism of the mutations in the new disease., (© 2022 The Authors. Published under the terms of the CC BY 4.0 license.)

Passive permeability of a drug-like molecule is a critical property assayed early in a drug discovery campaign that informs a medicinal chemist how well a compound can traverse biological membranes, such as gastrointestinal epithelial or restrictive organ barriers, so it can perform a specific therapeutic function. However, the challenge that remains is the development of a method, experimental or computational, which can both determine the permeation rate and provide mechanistic insights into the transport process to help with the rational design of any given molecule. Typically, one of the following three methods are used to measure the membrane permeability: (1) experimental permeation assays acting on either artificial or natural membranes; (2) quantitative structure-permeability relationship models that rely on experimental values of permeability or related pharmacokinetic properties of a range of molecules to infer those for new molecules; and (3) estimation of permeability from the Smoluchowski equation, where free energy and diffusion profiles along the membrane normal are taken as input from large-scale molecular dynamics simulations. While all these methods provide estimates of permeation coefficients, they provide very little information for guiding rational drug design. In this study, we employ a highly parallelizable weighted ensemble (WE) path sampling strategy, empowered by cloud computing techniques, to generate unbiased permeation pathways and permeability coefficients for a set of drug-like molecules across a neat 1-palmitoyl-2-oleoyl- sn -glycero-3-phosphatidylcholine membrane bilayer. Our WE method predicts permeability coefficients that compare well to experimental values from an MDCK-LE cell line and PAMPA assays for a set of drug-like amines of varying size, shape, and flexibility. Our method also yields a series of continuous permeation pathways weighted and ranked by their associated probabilities. Taken together, the ensemble of reactive permeation pathways, along with the estimate of the permeability coefficient, provides a clearer picture of the microscopic underpinnings of small-molecule membrane permeation.

Background: Pancreatic cancer is one of the most aggressive malignancies globally, with no improvement in the cure rates yet.Caveolin-2 (CAV2) has been repeatedly reported to play an important role in cellular transport and signalling and in exhibiting a pro-oncogenic response in a variety of tumours, although its specific action mechanisms in pancreatic cancer are not well documented. MiRNA is recognized as a therapeutic target for a variety of tumours, making it an important regulator of the Wnt/β-catenin signalling pathway. MiR-4723/Wnt7A constitutes an oncogenic signalling axis in pancreatic cancer by targeting and inhibiting Wnt7A through the activation of MiR4723, but its molecular action mechanism remains unexplored. Therefore, in the present study, we investigated the effect of CAV2 on the MiR-4723/Wnt7A pathway and its action mechanism. Methods: We employed TCGA, the GEO database for bioinformatics analysis, cell proliferation assay, wound healing assay, Transwell assay, colony-forming assay, qRT-PCR, and Western blotting to validate the cancer-promoting role of CAV2 in pancreatic cancer and to determine its potential target WNT7A. We then explored CAV2 as a positive regulator of the Wnt7A/β-catenin pathway through immunofluorescence assay, qRT-PCR, and Western blotting. Database analyses, CCK-8 and qRT-PCR revealed that MiR-4723 is an oncogene in pancreatic cancer. Luciferase assay and qRT-PCR revealed that MiR-4723 is a negative regulator of the Wnt7A/β-catenin pathway. To investigate the mechanism of CAV2 action on MiR-4723/Wnt7A, we detected the gene expression of CAV2 through qRT-PCR after MiR-4723 overexpression. Several genes related to endocytosis and epithelial-mesenchymal transition (EMT) were subsequently analysed through immunofluorescence, Western blotting, and qRT-PCR. Results: Overexpression of CAV2 promotes invasion, migration, cloning and metastasis of pancreatic cancer cells. Overexpression of MiR-4723 inhibits CAV2 expression. Here, we are the first to demonstrate that CAV2 exerts a pro-carcinogenic effect on pancreatic cancer through the activation of the Wnt7A/β-catenin signalling pathway. Conclusion: CAV2 can regulate the MiR-4723/Wnt7A signalling axis in pancreatic cancer cell lines by inhibiting endocytosis and promoting EMT, thereby fulfilling the mechanism pro-carcinogenic effects., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Although two Enhancer of Polycomb-like proteins, EPL1A and EPL1B (EPL1A/B), are known to be conserved and characteristic subunits of the NuA4-type histone acetyltransferase complex in Arabidopsis thaliana, the biological function of EPL1A/B and the mechanism by which EPL1A/B function in the complex remain unknown. Here, we report that EPL1A/B are required for the histone acetyltransferase activity of the NuA4 complex on the nucleosomal histone H4 in vitro and for the enrichment of histone H4K5 acetylation at thousands of protein-coding genes in vivo. Our results suggest that EPL1A/B are required for linking the NuA4 catalytic subunits HISTONE ACETYLTRANSFERASE OF THE MYST FAMILY 1（HAM1) and HAM2 with accessory subunits in the NuA4 complex. EPL1A/B function redundantly in regulating plant development especially in chlorophyll biosynthesis and de-etiolation. The EPL1A/B-dependent transcription and H4K5Ac are enriched at genes involved in chlorophyll biosynthesis and photosynthesis. We also find that EAF6, another characteristic subunit of the NuA4 complex, contributes to de-etiolation. These results suggest that the Arabidopsis NuA4 complex components function as a whole to mediate histone acetylation and transcriptional activation specifically at light-responsive genes and are critical for photomorphogenesis., (© 2022 Institute of Botany, Chinese Academy of Sciences.)

Methanobactins (Mbns) are a family of copper-binding peptides involved in copper uptake by methanotrophs, and are potential therapeutic agents for treating diseases characterized by disordered copper accumulation. Mbns are produced via modification of MbnA precursor peptides at cysteine residues catalyzed by the core biosynthetic machinery containing MbnB, an iron-dependent enzyme, and MbnC. However, mechanistic details underlying the catalysis of the MbnBC holoenzyme remain unclear. Here, we present crystal structures of MbnABC complexes from two distinct species, revealing that the leader peptide of the substrate MbnA binds MbnC for recruitment of the MbnBC holoenzyme, while the core peptide of MbnA resides in the catalytic cavity created by the MbnB-MbnC interaction which harbors a unique tri-iron cluster. Ligation of the substrate sulfhydryl group to the tri-iron center achieves a dioxygen-dependent reaction for oxazolone-thioamide installation. Structural analysis of the MbnABC complexes together with functional investigation of MbnB variants identified a conserved catalytic aspartate residue as a general base required for MbnBC-mediated MbnA modification. Together, our study reveals the similar architecture and function of MbnBC complexes from different species, demonstrating an evolutionarily conserved catalytic mechanism of the MbnBC holoenzymes., (© 2022. The Author(s).)

The present research attempts to understand the importance of altruistic and egoistic values in determining consumers' motives and intention to purchase organic foods. Using the face-to-face survey approach, a total of 1,067 responses were collected from consumers in China. Data analysis was performed using a two-step structural equation modeling (SEM) approach, i.e., measurement and structural models. The findings indicated that both values influence the intention to purchase organic foods through the mediation of motives. Specifically, the altruistic value influences the environmental concern (EC), and the egoistic value influences the health concern (HC). Moreover, the perceived uncertainty negatively moderates a relationship between consumer HC and organic purchase intention while positively moderating a relationship between consumer EC and organic purchase intention. Several implications and suggestions are also discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wei, Liu, She and Wu.)

Chemokines are a family of cytokines that orchestrate the migration and positioning of immune cells within tissues and are critical for the function of the immune system. CCR2 participates in liver pathology, including acute liver injury, chronic hepatitis, fibrosis/cirrhosis, and tumor progression, by mediating the recruitment of immune cells to inflammation and tumor sites. Although a variety of chemokines have been well studied in various diseases, there is no comprehensive review presenting the roles of all known chemokine ligands of CCR2 (CCL2, CCL7, CCL8, CCL12, CCL13, CCL16, and PSMP) in liver disease, and this review aims to fill this gap. The introduction of each chemokine includes its discovery, its corresponding chemotactic receptors, physiological functions and roles in inflammation and tumors, and its impact on different immune cell subgroups., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 She, Ren, Chen, Wang, Chen, Wang and Chen.)

The weighted ensemble (WE) family of methods is one of several statistical mechanics-based path sampling strategies that can provide estimates of key observables (rate constants and pathways) using a fraction of the time required by direct simulation methods such as molecular dynamics or discrete-state stochastic algorithms. WE methods oversee numerous parallel trajectories using intermittent overhead operations at fixed time intervals, enabling facile interoperability with any dynamics engine. Here, we report on the major upgrades to the WESTPA software package, an open-source, high-performance framework that implements both basic and recently developed WE methods. These upgrades offer substantial improvements over traditional WE methods. The key features of the new WESTPA 2.0 software enhance the efficiency and ease of use: an adaptive binning scheme for more efficient surmounting of large free energy barriers, streamlined handling of large simulation data sets, exponentially improved analysis of kinetics, and developer-friendly tools for creating new WE methods, including a Python API and resampler module for implementing both binned and "binless" WE strategies.

Developing a low-cost and efficient photocatalysts activated peroxymonosulfate (PMS) for organic pollutants degradation are recognized as an importance way for dealing with environmental pollution. In this work, Fe-rectorite catalyst was synthesized by a simple impregnation-calcine method to synergetic photo activate PMS for antibiotics degradation. As expected, the Fe-rectorite/PMS/Light system exhibits superior catalytic performance for tetracycline (TC) removal, which achieving 96.4% removal rate of TC (30 mg/L) under light within 60 min. Fe-retorite has better degradation performance for TC than rectorite under photo-mediation. The enhancement of the degradation performance of TC by Fe-retorite can be attributed to the improvement of the separation efficiency of photogenerated electrons and holes in the rectorite by the loading of Fe 2 O 3 , and the accelerated active Fe(Ⅱ)/Fe(Ⅲ) cycle on the surface under photo-mediation. The large specific surface area and abundant hydroxyl groups of rectorite can also provide active sites for PMS activation. The quenching experiment and electron paramagnetic resonance (EPR) test were indicated that the h + , SO 4 • - , •OH, and O 2 - • all contributed to TC degradation. And the possible degradation pathway was proposed by LC-MS. This work helps induced a novel direction that design green, efficient, and recyclable heterogeneous catalysts to synergetic photoinduced PMS activation for enhanced degradation of TC., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: Paclitaxel, belongs to tubulin-binding agents (TBAs), shows a great efficacy against breast cancer via stabilizing microtubules. Drug resistance limits its clinical application. Here we aimed to explore a role of Polarity protein Par3 in improving paclitaxel effectiveness., Methods: Breast cancer specimens from 45 patients were collected to study the relationship between Par3 expression and paclitaxel efficacy. The Kaplan-Meier method was used for survival analysis. Cell viability was measured in breast cancer cells (SK-BR-3 and T-47D) with Par3 over-expression or knockdown. The flow cytometry assays were performed to measure cell apoptosis and cell cycle. BrdU incorporation assay and Hoechst 33,258 staining were performed to measure cell proliferation and cell apoptosis, respectively. Immunofluorescence was used to detect microtubule structures., Results: Par3 expression was associated with good response of paclitaxel in breast cancer patients. Consistently, Par3 over-expression significantly sensitized breast cancer cells to paclitaxel by promoting cell apoptosis and reducing cell proliferation. In Par3 overexpressing cells upon paclitaxel treatment, we observed intensified cell cycle arrests at metaphase. Further exploration showed that Par3 over-expression stabilized microtubules of breast cancer cells in response to paclitaxel and resists to microtubules instability induced by nocodazole, a microtubule-depolymerizing agent., Conclusion: Par3 facilitates polymeric forms of tubulin and stabilizes microtubule structure, which aggravates paclitaxel-induced delay at the metaphase-anaphase transition, leading to proliferation inhibition and apoptosis of breast cancer cells. Par3 has a potential role in sensitizing breast cancer cells to paclitaxel, which may provide a more precise assessment of individual treatment and novel therapeutic targets., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: This study aims to evaluate the safety, utilization, ability to reduce length of hospitalization and overall outcomes of a COVID-19 virtual ward providing ongoing treatment at home., Method: A retrospective single-center study of patients discharged to the COVID-19 virtual "step down" ward between January 27th 2021 and March 2nd 2021. The referral process, length of hospitalization, length of stay on the virtual ward, readmissions, and ongoing treatment requirements including supplemental oxygen, antibiotics, and/or steroids were all noted., Results: A total of 50 patients were referred to the virtual ward. 43 referrals were accepted, 39 of which were from the respiratory ward. Four patients were readmitted, all due to hypoxia. All readmissions occurred within 5 days of discharge. 72% (n = 31) were discharged home with an ongoing oxygen requirement. 14.3% of patients were discharged with antibiotics only, 9.5% with steroids only and 23.8% with both antibiotics and steroids. The mean length of hospital stay for patients discharged to the virtual ward was 10.3 ± 9.7 days and 11.9 ± 11.6 days for all covid positive patients during this time. On average, patients spent 13.7 ± 7.3 days on the virtual ward. The average number of days spent on oxygen on the virtual ward was 11.6 ± 6.0 days., Conclusion: The virtual ward model exemplifies the potential benefits of collaborative working between primary and secondary care services, relieving pressure on hospitals whilst providing ongoing treatments at home such as supplemental oxygen. It also facilitates an early supported discharge of clinically stable patients with an improving clinical trajectory by managing them in the community.

Background: The main aim of this study was to assess the efficacy of advanced respiratory support (ARS) for acute respiratory failure in do-not-attempt cardiopulmonary resuscitation order (DNACPR) COVID-19 patients. Methods: In this single-center study, the impact of different types of ARS modality, PaO 2 /FiO 2 (PF) ratio, clinical frailty score (CFS) and 4C score on mortality was evaluated. Results: There was no significant difference in age, type of ARS modality, PF ratio and 4C scores between those who died and those who survived. Overall survival rates/hospital discharge of patients still requiring ARS at 5 and 7 days post admission were 20 and 17%, respectively. Conclusion: Our study showed that ARS can be a useful tool in frail, elderly and high-risk COVID-19 patients irrespective of high 4C mortality score.

With the advancing of location-detection technologies and the increasing popularity of mobile phones and other location-aware devices, trajectory data is continuously growing. While large-scale trajectories provide opportunities for various applications, the locations in trajectories pose a threat to individual privacy. Recently, there has been an interesting debate on the reidentifiability of individuals in the Science magazine. The main finding of Sánchez et al. is exactly opposite to that of De Montjoye et al. , which raises the first question: "what is the true situation of the privacy preservation for trajectories in terms of reidentification?" Furthermore, it is known that anonymization typically causes a decline of data utility, and anonymization mechanisms need to consider the trade-off between privacy and utility. This raises the second question: "what is the true situation of the utility of anonymized trajectories?" To answer these two questions, we conduct a systematic experimental study, using three real-life trajectory datasets, five existing anonymization mechanisms (i.e., identifier anonymization, grid-based anonymization, dummy trajectories, k -anonymity and ε -differential privacy), and two practical applications (i.e., travel time estimation and window range queries). Our findings reveal the true situation of the privacy preservation for trajectories in terms of reidentification and the true situation of the utility of anonymized trajectories, and essentially close the debate between De Montjoye et al. and Sánchez et al. To the best of our knowledge, this study is among the first systematic evaluation and analysis of anonymized trajectories on the individual privacy in terms of unicity and on the utility in terms of practical applications., Supplementary Information: The online version contains supplementary material available at 10.1007/s11390-022-2409-x., (© Institute of Computing Technology, Chinese Academy of Sciences 2022.)

Electrochemical CO 2 reduction (ECR) technology is promising to produce value-added chemicals and alleviate the climate deterioration. Interface engineering is demonstrated to improve the ECR performance for metal and oxide composite catalysts. However, the approach to form a substantial interface is still limited. In this work, we report a facile one-pot coprecipitation method to synthetize novel silver and silver-doped ceria (Ag/CeO 2 ) nanocomposites. This catalyst provides a rich 3D interface and high Ce 3+ concentration (33.6%), both of which are beneficial for ECR to CO. As a result, Ag/CeO 2 exhibits a 99% faradaic efficiency and 10.5 A g -1 mass activity to convert CO 2 into CO at an overpotential of 0.83 V. The strong interfacial interaction between Ag and CeO 2 may enable the presence of surface Ce 3+ and guarantee the improved durability during the electrolysis. We also develop numerical simulation to understand the local pH effect on the ECR performance and propose that the superior ECR performance of Ag/CeO 2 is mainly due to the accelerated CO formation rate rather than the suppressed hydrogen evolution reaction.

Deciphering the regulatory network for human naive and primed pluripotency is of fundamental theoretical and applicable significance. Here, by combining quantitative proteomics, phosphoproteomics, and acetylproteomics analyses, we revealed RNA processing and translation as the most differentially regulated processes between naive and primed human embryonic stem cells (hESCs). Although glycolytic primed hESCs rely predominantly on the eukaryotic initiation factor 4E (eIF4E)-mediated cap-dependent pathway for protein translation, naive hESCs with reduced mammalian target of rapamycin complex (mTORC1) activity are more tolerant to eIF4E inhibition, and their bivalent metabolism allows for translating selective mRNAs via both eIF4E-dependent and eIF4E-independent/eIF4A2-dependent pathways to form a more compact naive proteome. Globally up-regulated proteostasis and down-regulated post-translational modifications help to further refine the naive proteome that is compatible with the more rapid cycling of naive hESCs, where CDK1 plays an indispensable coordinative role. These findings may assist in better understanding the unrestricted lineage potential of naive hESCs and in further optimizing conditions for future clinical applications., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Mixed lineage leukemia 1 (MLL1) is a histone methyltransferase. Kaposi's sarcoma-associated herpesvirus (KSHV) is a leading cause of malignancy in AIDS. KSHV latently infects tumor cells and its genome is decorated with epigenetic marks. Here, we show that KSHV latency-associated nuclear antigen (LANA) recruits MLL1 to viral DNA where it establishes H3K4me3 modifications at the extensive KSHV terminal repeat elements during primary infection. LANA interacts with MLL1 complex members, including WDR5, integrates into the MLL1 complex, and regulates MLL1 activity. We describe the 1.5-Å crystal structure of N-terminal LANA peptide complexed with MLL1 complex member WDR5, which reveals a potential regulatory mechanism. Disruption of MLL1 expression rendered KSHV latency establishment highly deficient. This deficiency was rescued by MLL1 but not by catalytically inactive MLL1. Therefore, MLL1 is LANA regulable and exerts a central role in virus infection. These results suggest broad potential for MLL1 regulation, including by non-host factors., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

With the advance of genome engineering technology, chimeric antigen receptors (CARs)-based immunotherapy has become an emerging therapeutic strategy for tumors. Although initially designed for T cells in tumor immunotherapy, CARs have been exploited to modify the function of natural killer (NK) cells against a variety of tumors, including hepatocellular carcinoma (HCC). CAR-NK cells have the potential to sufficiently kill tumor antigen-expressing HCC cells, independent of major histocompatibility complex matching or prior priming. In this review, we summarize the recent advances in genetic engineering of CAR-NK cells against HCC and discuss the current challenges and prospects of CAR-NK cells as a revolutionary cellular immunotherapy against HCC., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Photocatalytic CO 2 reduction is typically limited by the separation efficiency of photogenerated carriers for a single semiconductor. Thus, fabricating a two-dimensional/two-dimensional (2D/2D) heterojunction photocatalyst with high separation efficiency of photogenerated carriers has become a research priority. Here, a 2D/2D g-C 3 N 4 /NaBiO 3 ·2H 2 O (CN/NBO) heterojunction photocatalyst was successfully synthesized for CO 2 photoreduction. With the assistance of the nature of CN, the 10CN/NBO composite showed the best performance with the production yield rates of 110.2 and 43.8 µmol g -1 for CO and CH 4 , respectively. Our experiments showed that the introduction of CN in CN/NBO composites, which is under the step-scheme (S-step) transfer direction of photogenerated carriers, could greatly inhibit the recombination of photogenerated e - -h + pairs to prolong the carriers' lifetime, which was further confirmed by analysis of photoluminescence and photochemical characterization. As we expected, the CN/NBO composites show improved photocatalytic CO 2 reduction activity. The in situ infrared spectroscopy was also performed to study the intermediate products of the photocatalytic CO 2 reduction process. This study provides a way to design CN-based heterojunction photocatalysts for CO 2 photoreduction., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Summary: Efficient sampling of conformational space is essential for elucidating functional/allosteric mechanisms of proteins and generating ensembles of conformers for docking applications. However, unbiased sampling is still a challenge especially for highly flexible and/or large systems. To address this challenge, we describe a new implementation of our computationally efficient algorithm ClustENMD that is integrated with ProDy and OpenMM softwares. This hybrid method performs iterative cycles of conformer generation using elastic network model for deformations along global modes, followed by clustering and short molecular dynamics simulations. ProDy framework enables full automation and analysis of generated conformers and visualization of their distributions in the essential subspace., Availability and Implementation: ClustENMD is open-source and freely available under MIT License from https://github.com/prody/ProDy., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2021. Published by Oxford University Press.)

Summary: ProDy, an integrated application programming interface developed for modelling and analysing protein dynamics, has significantly evolved in recent years in response to the growing data and needs of the computational biology community. We present major developments that led to ProDy 2.0: (i) improved interfacing with databases and parsing new file formats, (ii) SignDy for signature dynamics of protein families, (iii) CryoDy for collective dynamics of supramolecular systems using cryo-EM density maps and (iv) essential site scanning analysis for identifying sites essential to modulating global dynamics., Availability and Implementation: ProDy is open-source and freely available under MIT License from https://github.com/prody/ProDy., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2021. Published by Oxford University Press.)

With the intensification of global warming, rice production is facing new challenges. Field evidence indicates that elevated temperature during rice grain-filling leads to the further deterioration of grain quality. In order to clarify the potential regulatory mechanism of elevated temperature on the formation of rice quality, the DIA mass spectrometry method under the background of field warming was conducted to investigate the regulatory effects of high temperature on grain development and material accumulation pathways. The results showed that a total of 840 differentially expressed proteins were identified during the grain-filling process under elevated temperature. These differentially expressed proteins participated in carbon metabolism, amino acid biosynthesis, signal transduction, protein synthesis, and alternately affected the material accumulation of rice grains. The significant up-regulation of PPROL 14E, PSB28, granule-bound starch synthase I, and the significant down-regulation of 26.7 kDa heat shock protein would lead to the component difference in grain starch and storage proteins, and that could be responsible for the degradation of rice quality under elevated temperature. Results suggested that proteins specifically expressed under elevated temperature could be the key candidates for elucidating the potential regulatory mechanism of warming on rice development and quality formation. In-depth study on the metabolism of storage compounds would be contributed in further proposing high-quality cultivation control measures suitable for climate warming., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Yin, Zhao, Wang, Wang, Shen, Ding and Tang.)

In the INO80 chromatin remodeling complex, all of the accessory subunits are assembled on the following three domains of INO80: N-terminal domain (NTD), HSA domain, and ATPase domain. Although the ATPase and HSA domains and their interacting accessory subunits are known to be responsible for chromatin remodeling, it is largely unknown how the accessory subunits that interact with the INO80 NTD regulate chromatin status. Here, we identify both conserved and nonconserved accessory subunits that interact with the three domains in the INO80 complex in Arabidopsis thaliana. While the accessory subunits that interact with all the three INO80 domains can mediate transcriptional repression, the INO80 NTD and the accessory subunits interact with it can contribute to transcriptional activation even when the ATPase domain is absent, suggesting that INO80 has an ATPase-independent role. A subclass of the COMPASS histone H3K4 methyltransferase complexes interact with the INO80 NTD in the INO80 complex and function together with the other accessory subunits that interact with the INO80 NTD, thereby facilitating H3K4 trimethylation and transcriptional activation. This study suggests that the opposite effects of the INO80 complex on transcription are required for the balance between vegetative growth and flowering under diverse environmental conditions., (� American Society of Plant Biologists 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Detection of transient changes in interaural correlation is based on the temporal precision of the central representations of acoustic signals. Whether schizophrenia impairs the temporal precision in the interaural correlation process is not clear. In both participants with schizophrenia and matched healthy-control participants, this study examined the detection of a break in interaural correlation (BIC, a change in interaural correlation from 1 to 0 and back to 1), including the longest interaural delay at which a BIC was just audible, representing the temporal extent of the primitive auditory memory (PAM). Moreover, BIC-induced electroencephalograms (EEGs) and the relationships between the early binaural psychoacoustic processing and higher cognitive functions, which were assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), were examined. The results showed that compared to healthy controls, participants with schizophrenia exhibited poorer BIC detection, PAM and RBANS score. Both the BIC-detection accuracy and the PAM extent were correlated with the RBANS score. Moreover, participants with schizophrenia showed weaker BIC-induced N1-P2 amplitude which was correlated with both theta-band power and inter-trial phase coherence. These results suggested that schizophrenia impairs the temporal precision of the central representations of acoustic signals, affecting both interaural correlation processing and higher-order cognitions., (© 2021 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Rab3a, a subtype protein in the Rab3 family amongst the small G proteins, is closely associated with the learning and memory formation process. Various neuronal stimuli can induce the expression of Rab3a; however, how DNA modification is involved in regulating its expression is not fully understood. Ten-eleven translocation (TET) proteins can oxidate methylcytosine to hydroxymethylcytosine, which can further activate gene expression. Previous studies reported that TET-mediated regulation of 5hmC induced by learning is involved in neuronal activation. However, whether Tet protein regulates Rab3a is unknown. To understand the role of TET-mediated 5hmC on Rab3a in neuronal activation, we adopted a KCl-induced depolarization protocol in cultured primary cortical neurons to mimic neuronal activity in vitro . After KCl treatment, Rab3a and Tet3 mRNA expression were induced. Moreover, we observed a decrease in the methylation level and an increase of hydroxymethylation level surrounding the CpG island near the transcription start site of Rab3a. Furthermore, recently, Formaldehyde-Assisted Isolation of Regulatory Elements (FAIRE) has proven powerful in identifying open chromatin in the genome of various eukaryotes. Using FAIRE-qPCR, we observed a euchromatin state and the increased occupancy of Tet3, H3K4me3, and H3K27ac at the promoter region of Rab3a after KCl treatment. Finally, by using shRNA to knockdown Tet3 prior KCl treatment, all changes mentioned above vanished. Thus, our findings elucidated that the neuronal activity-induced accumulation of hydroxymethylation, which Tet3 mediates, can introduce an active and permissive chromatin structure at Rab3a promoter and lead to the induction of Rab3a mRNA expression., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s). Published by IMR Press.)

Research has shown that the extent to which previous environmental actions are linked to people's environmental self-identity influences subsequent environmentally-friendly behaviour. The study empirically examined the influences of recycling efforts on subsequent pro-environmental behaviour by PLS (partial least squares) structural equation modelling based on the survey data of 426 respondents in China. The results indicate that recycling efforts have a positive effect on pro-environmental behaviour through the mechanism of feelings of pride and environmental self-identity. We hypothesise that past pro-environmental behaviour is more likely to promote an individual's environmental self-identity when the behaviour is incurred with a higher costliness. However, the results show that only when individuals autonomously perform costly recycling behaviour, the signalling strength of previous recycling efforts is higher to promote environmental self-identity. On the contrary, the high costliness weakens the signalling strength of previous recycling efforts through producing negative emotions. Our results show that when reminding people of their past pro-environmental behaviour in order to promote future pro-environmental behaviour, it is useful to emphasize the autonomously taken costliness of behaviour as it can strongly signal that one is a pro-environmental person, thus as to strengthen environmental self-identity.

The extent of retrogradation strongly affects certain physical and cooking properties of rice starch (RS), which are important to consumers. In this study, oligomeric procyanidins from lotus seedpod (LSOPC) was prepared and used to investigate its inhibitory effect on RS retrogradation. Various structural changes of RS during retrogradation were characterized by differential scanning calorimetry, low field nuclear magnetic resonance, X-ray diffraction, scanning electron microscopy, and Fourier transform infrared spectroscopy. The results showed LSOPC could effectively retard both short- and long-term retrogradation of RS, and its inhibitory effect was dependent on the administered concentration of LSOPC. Molecule simulation revealed the interactions of RS and LSOPC, which indicated that the competition of hydrogen bonds between RS and LSOPC was the critical factor for anti-retrogradation. This inhibitory effect and mechanism of action of LSOPC could promote its applications in the field of starch anti-retrogradation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Feng, She, Hu, Tang, Tan, Wu and Xiao.)

We present a case of black pleural fluid following thoracic trauma. The unusual dark colour most strikingly resembled soy sauce as independently commented upon by multiple treating physicians. The black colouration could not be fully accounted for by haemothorax or cholethorax, so other differential diagnoses were investigated, including Aspergillus niger infection and malignant melanoma. The cause, however, was thought to be due to staining of the fluid with carbon deposited in the pleural space from the non-volatilised impurities from smoking crack cocaine. A novel use of a point-of-care urine toxicology assay confirmed the presence of cocaine in the pleural fluid. Considering a broad range of differential diagnoses is needed to avoid missing important causes of unusual pleural effusions., (© Royal College of Physicians 2021. All rights reserved.)

Our previous study has shown that nitrogen plays an important role in dealing with significantly increased chalkiness caused by elevated temperature. However, the role of nitrogen metabolites has not been given sufficient attention, and its regulatory mechanism is not clear. This study investigated the effects of high temperature and nitrogen fertilizer on the synthesis of grain storage protein and further explored the quality mechanism under the actual scenario of field warming. Results showed that increased temperature and nitrogen fertilizer could affect the activities of nitrogen metabolism enzymes, namely, glutamate synthetase, glutamine synthetase, glutamic pyruvic transaminase, and glutamic oxaloacetic transaminase, and the expressions of storage protein synthesis factor genes, namely, GluA and GluB , and subfamily genes, namely, pro14, BiP1 , and PDIL1 , which co-induced the changes of storage protein synthesis in rice grains. Furthermore, the increased temperature changed the balance of grain storage substances which may lead to the significantly increased chalky rate (197.67%) and chalkiness (532.92%). Moreover, there was a significant negative correlation between prolamin content and chalkiness, indicating that nitrogen fertilizer might regulate the formation of chalkiness by affecting the synthesis of prolamin. Results suggested that nitrogen application could regulate the related core factors involved in nitrogen metabolism pathways, which, in turn, affects the changes in the storage protein components in the grain and further affects quality. Therefore, as a conventional cultivation measure, nitrogen application would have a certain value in future rice production in response to climate warming., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Wang, Yin, Zhao, Liu, Shen, Ding and Tang.)

Background: Long noncoding RNAs (lncRNAs), a type of pervasive genes that regulates various biological processes, are differentially expressed in different types of malignant tumors. The role of lncRNAs in the carcinogenesis of pancreatic ductal adenocarcinoma (PDAC) remains unclear. Here, we investigated the role of the lncRNA DKFZp434J0226 in PDAC., Methods: Aberrantly expressed mRNAs and lncRNAs among six PDAC and paired non-tumorous tissues were profiled using microarray analysis. Quantitative real-time polymerase chain reaction was used to evaluate DKFZp434J0226 expression in PDAC tissues. CCK-8 assay, wound-healing assay, soft agar colony formation assay, and transwell assay were performed to assess the invasiveness and proliferation of PDAC cells. Furthermore, RNA pull-down, immunofluorescence, RNA immunoprecipitation, and western blotting assays were performed to investigate the association between DKFZp434J0226 and SF3B6. Tumor xenografts in mice were used to test for tumor formation in vivo., Results: In our study, 222 mRNAs and 128 lncRNAs were aberrantly expressed (≥ twofold change). Of these, 66 mRNAs and 53 lncRNAs were upregulated, while 75 lncRNAs and 156 mRNAs were downregulated. KEGG pathway analysis and the Gene ontology category indicated that these genes were associated with the regulation of mRNA alternative splicing and metabolic balance. Clinical analyses revealed that overexpression of DKFZp434J0226 was associated with worse tumor grading, frequent perineural invasion, advanced tumor-node-metastasis stage, and decreased overall survival and time to progression. Functional assays demonstrated that DKFZp434J0226 promoted PDAC cell migration, invasion, and growth in vitro and accelerated tumor proliferation in vivo. Mechanistically, DKFZp434J0226 interacted with the splicing factor SF3B6 and promoted its phosphorylation, which further regulated the alternative splicing of pre-mRNA., Conclusions: This study indicates that DKFZp434J0226 regulates alternative splicing through phosphorylation of SF3B6 in PDAC and leads to an oncogenic phenotype in PDAC., (© 2021. The Author(s).)

Melatonin mediates multiple physiological processes in plants and is involved in many reactions related to the protection of plants from abiotic stress. In this paper, the effect of melatonin on the antioxidant capacity of rice under salt stress was studied. Melatonin alleviated the inhibition of salt stress on the growth of rice seedlings, mainly by increasing the dry weight and fresh weight of shoots and roots. Melatonin alleviated the membrane damage caused by salt stress, which was mainly manifested by the decrease of TBARS content and the decrease of leaf and root damage. During the whole salt stress period, rice after melatonin pretreatment showed lower ROS (H 2 O 2 , O 2 •- ,OH - ) accumulation. In the early stage (1-3 d) of stress, the rice after melatonin pretreatment showed a strong increase in antioxidant enzyme activity, while in the later stage (5,7 d), it showed a strong increase in antioxidant content. During the whole period of salt stress, melatonin had a weak regulatory effect on AsA-GSH cycle. Through the above regulation process, the decreasing effect of melatonin on ROS content of rice under salt stress did not decrease with prolonged stress time in a short time (1-7 d). In conclusion, melatonin improved the antioxidant capacity of rice under continuous salt stress, and rice showed variable antioxidant strategies after melatonin pretreatment., (Copyright © 2021. Published by Elsevier Masson SAS.)

Aim: COVID-19 is a known risk factor for pulmonary embolism (PE). In this retrospective, multicenter study, we aimed to determine an optimal D-dimer cutoff to predict PE in hospitalized patients with COVID-19. Materials & methods: A total of 193 patients underwent computerized tomographic pulmonary angiography imaging and were classified into PE positive and negative groups. Physiological, radiological and biochemical parameters were compared and receiver operator curve analysis was conducted to determine a predictive D-dimer threshold. Results: An optimal D-dimer cutoff of 2494 ng/ml was selected (Youden index: 0.906), giving a sensitivity of 100% (95% CI: 100-100) and specificity of 90.62% (95% CI: 90.5-90.8) for predicting PE. Conclusion: We propose that in the absence of other clinical signs, a D-dimer threshold of 2495 ng/ml could be used with high sensitivity and specificity to predict PE in hospitalized patients with COVID-19.

Cellulose is one of the most abundant organic polymers in nature. It contains multiple β-1,4-glucan chains synthesized by cellulose synthases (CesAs) on the plasma membrane of higher plants. CesA subunits assemble into a pseudo-sixfold symmetric cellulose synthase complex (CSC), known as a 'rosette complex'. The structure of CesA remains enigmatic. Here, we report the cryo-EM structure of the homotrimeric CesA7 from Gossypium hirsutum at 3.5-angstrom resolution. The GhCesA7 homotrimer shows a C3 symmetrical assembly. Each protomer contains seven transmembrane helices (TMs) which form a channel potentially facilitating the release of newly synthesized glucans. The cytoplasmic glycosyltransferase domain (GT domain) of GhCesA7 protrudes from the membrane, and its catalytic pocket is directed towards the TM pore. The homotrimer GhCesA7 is stabilized by the transmembrane helix 7 (TM7) and the plant-conserved region (PCR) domains. It represents the building block of CSCs and facilitates microfibril formation. This structure provides insight into how eukaryotic cellulose synthase assembles and provides a mechanistic basis for the improvement of cotton fibre quality in the future., (© 2021 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

The SAGA (Spt-Ada-Gcn5 acetyltransferase) complex is an evolutionarily conserved histone acetyltransferase complex that has a critical role in histone acetylation, gene expression, and various developmental processes in eukaryotes. However, little is known about the composition and function of the SAGA complex in plants. In this study, we found that the SAGA complex in Arabidopsis thaliana contains not only conserved subunits but also four plant-specific subunits: three functionally redundant paralogs, SCS1, SCS2A, and SCS2B (SCS1/2A/2B), and a TAF-like subunit, TAFL. Mutations in SCS1/2A/2B lead to defective phenotypes similar to those caused by mutations in the genes encoding conserved SAGA subunits HAG1 and ADA2B, including delayed juvenile-to-adult phase transition, late flowering, and increased trichome density. Furthermore, we demonstrated that SCS1/2A/2B are required for the function of the SAGA complex in histone acetylation, thereby promoting the transcription of development-related genes. These results together suggest that SCS1/2A/2B are core subunits of the SAGA complex in Arabidopsis. Compared with SAGA complexes in other eukaryotes, the SAGA complexes in plants have evolved unique features that are necessary for normal growth and development., (Copyright © 2021 The Author. Published by Elsevier Inc. All rights reserved.)

Loss of polarity protein Par3 promotes breast cancer tumorigenesis and metastasis. The underlying molecular mechanisms of Par3 down-regulation and related prognostic significance in breast cancer remain unclear. Here, we discovered that Par3 down-regulation was associated with shorter relapse-free survival in Luminal A subtype of breast cancer. Par3 knockdown promoted breast cancer cells migration and invasion. Importantly, we identified that transcription factor Sp1 bound to PARD3 promoter region and induced Par3 expression. Breast cancer patients with low Sp1 showed significantly worse RFS and low expression level of Par3. Par3 over-expression partially reversed Sp1 knockdown induced migration and invasion. Together, decreased Sp1 level mediates Par3 down-regulation, which correlated with poor prognosis of ER + breast cancer patients, via reduced binding with PARD3 promoter., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Increasing use of organophosphorus flame retardants (OPFRs) has aroused great concern to their uncertain environment risk, especially to human health risk. In our study, hepatotoxicity screening of six aryl-OPFRs, potential hepatotoxicity mechanism of 2-ethylhexyldiphenyl phosphate (EHDPP) using RNA-sequencing and its metabolites were investigated in human hepatocytes (L02). The toxicity results demonstrated that EHDPP should be prioritized for further research with the highest toxicity. Further RNA-seq results through GO and KEGG enrichment analysis indicated that exposure to 10 mg/L of EHDPP significantly affected energy homeostasis, endoplasmic reticulum (ER) stress, apoptosis, cell cycle, and inflammation response in cells. The top 12 hub genes were validated by RT-qPCR and conformed to be mainly related to glycolysis and ER stress, followed by cell cycle and inflammation response. Western blot, apoptosis detection, glycolysis stress test, and cell cycle analysis were further performed to verify the above main pathways. Additionally, it was found in the metabolism experiment that detoxification of EHDPP by phase I and phase II metabolism in cells wasn't significant until 48 h with a metabolic rate of 6.12%. EHDPP was stable and still dominated the induction of toxicity. Overall, this study provided valuable information regarding the toxicity and potential metabolism pathway of EHDPP., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Bladder cancer (BLCA) remains the leading cause of cancer-related mortality among genitourinary malignancies worldwide. BLCA metastasis represents the primary reason for its poor prognosis. In this study, we report that decreased expression of partitioning defective 3 (Par3), a polarity protein (encoded by PARD3), is associated with tumor aggressive phenotypes and poor prognosis in BLCA patients. Consistently, ablation of Par3 promotes the metastasis and invasion of BLCA cells in vitro and in vivo. Further studies reveal that zinc finger protein Snail represses the expression of Par3 by binding to E2-box (CAGGTG) of PARD3 promoter-proximal. Inhibition of GSK-3β promotes the expression and nuclear localization of Snail and then reduces the expression of Par3, resulting in the metastasis and invasion of BLCA cells. Moreover, we detected the interaction between Par3 (936-1356 aa) and ZO-1 (1372-1748 aa), which is involved in the maintenance of tight junction. Together, our results demonstrate that the GSK-3β/Snail/Par3/ZO-1 axis regulates BLCA metastasis, and Snail is a major regulator for Par3 protein expression in BLCA., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Patients with Crohn's disease (CD) are inclined to have platelet hyperactivity and an increased risk of intestinal micro-thrombosis. However, the mechanisms underlying platelet hyperactivity in CD are not well understood. We investigated the assembly of platelet NLRP3 inflammasome in patients with active CD and its correlation with platelet hyperactivity. In this study, Real-time PCR and western blotting analyses uncovered that ASC, NLRP3, and active caspase-1 were significantly upregulated in platelets from patients with active CD compared with healthy subjects. As revealed by flow cytometry (FCM) and ELISA analyses, the levels of interleukin-1β in both serum and isolated platelets were elevated in patients with active CD. Co-immunoprecipitation and immunofluorescence experiments revealed an increased assembly of NLRP3 inflammasome in platelets from patients with active CD. In addition, higher levels of intracellular reactive oxygen species (ROS) were observed in these platelets by FCM. Furthermore, elevated levels of platelet P-selectin exposure and fibrinogen binding were demonstrated in patients with active CD by FCM. They were positively correlated with the protein levels of NLRP3 inflammasome components. Collectively, our results indicate that the ROS-NLRP3 inflammasome-interleukin-1β axis may contribute to platelet hyperactivity in active CD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Chen, Guo, Zhang, Jiang, Zhang, Han, Chen and Xue.)

The histone chaperone facilitates chromatin transactions (FACT) functions in various DNA transactions. How FACT performs these multiple functions remains largely unknown. Here, we found, for the first time, that the N-terminal domain of its Spt16 subunit interacts with the Set3 histone deacetylase complex (Set3C) and that FACT and Set3C function in the same pathway to regulate gene expression in some settings. We observed that Spt16-G132D mutant proteins show defects in binding to Set3C but not other reported FACT interactors. At the permissive temperature, induction of the GAL1 and GAL10 genes is reduced in both spt16-G132D and set3Δ cells, whereas transient upregulation of GAL10 noncoding RNA (ncRNA), which is transcribed from the 3' end of the GAL10 gene, is elevated. Mutations that inhibit GAL10 ncRNA transcription reverse the GAL1 and GAL10 induction defects in spt16-G132D and set3Δ mutant cells. Mechanistically, set3Δ and FACT (spt16-G132D) mutants show reduced histone acetylation and increased nucleosome occupancy at the GAL1 promoter under inducing conditions and inhibition of GAL10 ncRNA transcription also partially reverses these chromatin changes. These results indicate that FACT interacts with Set3C, which in turn prevents uncontrolled GAL10 ncRNA expression and fine-tunes the expression of GAL genes upon a change in carbon source., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: Due to its unique flexible and dexterity, continuum robot has been widely used in small constrained environment. However, those advantages also bring that motion modelling and accurate control for the continuum robot is more complicated and tedious. A dynamic model and control strategy is presented for improving its control performance., Methods: The kinematics and velocity model of the robot are derived. The inertial force, elastic force, gravity and actuation force applied to the continuum robot are analysed. Meanwhile, the friction in drive system is investigated, and dynamic model is established by the Kane's method. Finally, a motion control strategy is proposed based on this model to verify the dynamic model., Results: Results of the simulation and experiment of a prototype verify the proposed model and its control method., Conclusions: The proposed model and control strategy can be used to achieve the bending deformation of the robot., (© 2021 John Wiley & Sons Ltd.)

FAM19A5/TAFA5 is a member of the family with sequence similarity 19 with unknown function in emotional and cognitive regulation. Here, we reported that FAM19A5 was highly expressed in the embryonic and postnatal mouse brain, especially in the hippocampus. Behaviorally, genetic deletion of Fam19a5 resulted in increased depressive-like behaviors and impaired hippocampus-dependent spatial memory. These behavioral alterations were associated with the decreased expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors and N-methyl-D-aspartic acid receptors, as well as significantly reduced glutamate release and neuronal activity in the hippocampus. Subsequently, these changes led to the decreased density of dendritic spines. In recent years, the roles of chronic stress participating in the development of depression have become increasingly clear, but the mechanism remains to be elucidated. We found that the levels of FAM19A5 in plasma and hippocampus of chronic stress-treated mice were significantly decreased whereas overexpression of human FAM19A5 selectively in the hippocampus could attenuate chronic stress-induced depressive-like behaviors. Taken together, our results revealed for the first time that FAM19A5 plays a key role in the regulation of depression and spatial cognition in the hippocampus. Furthermore, our study provided a new mechanism for chronic stress-induced depression, and also provided a potential biomarker for the diagnosis and a new strategy for the treatment of depression., (© 2020. The Author(s), under exclusive licence to Springer Nature Limited.)

Receptor-interacting serine/threonine-protein kinase 3 (RIPK3) normally signals to necroptosis by phosphorylating MLKL. We report here that when the cellular RIPK3 chaperone Hsp90/CDC37 level is low, RIPK3 also signals to apoptosis. The apoptotic function of RIPK3 requires phosphorylation of the serine 165/threonine 166 sites on its kinase activation loop, resulting in inactivation of RIPK3 kinase activity while gaining the ability to recruit RIPK1, FADD, and caspase-8 to form a cytosolic caspase-activating complex, thereby triggering apoptosis. We found that PGF 2α induces RIPK3 expression in luteal granulosa cells in the ovary to cause luteal regression through this RIPK3-mediated apoptosis pathway. Mice carrying homozygous phosphorylation-resistant RIPK3 S165A/T166A knockin mutations failed to respond to PGF 2α but retained pro-necroptotic function, whereas mice with phospho-mimicking S165D/T166E homozygous knock-in mutation underwent spontaneous apoptosis in multiple RIPK3-expressing tissues and died shortly after birth. Thus, RIPK3 signals to either necroptosis or apoptosis depending on its serine 165/threonine 166 phosphorylation status., Competing Interests: DL, JC, JG, LL, GC, SC, JH, HY, YZ, FW, XW No competing interests declared, (© 2021, Li et al.)

The vibrational subsystem analysis is a useful approach that allows for evaluating the spectrum of modes of a given system by integrating out the degrees of freedom accessible to the environment. The approach could be utilized for exploring the collective dynamics of a membrane protein (system) coupled to the lipid bilayer (environment). However, the application to membrane proteins is limited due to high computational costs of modeling a sufficiently large membrane environment unbiased by end effects, which drastically increases the size of the investigated system. We derived a recursive formula for calculating the reduced Hessian of a membrane protein embedded in a lipid bilayer by decomposing the membrane into concentric cylindrical domains with the protein located at the center. The approach allows for the design of a time- and memory-efficient algorithm and a mathematical understanding of the convergence of the reduced Hessian with respect to increasing membrane sizes. The application to the archaeal aspartate transporter Glt Ph illustrates its utility and efficiency in capturing the transporter's elevator-like movement during its transition between outward-facing and inward-facing states.

The Arabidopsis thaliana RPD3-type histone deacetylases have been known to form conserved SIN3-type histone deacetylase complexes, but whether they form other types of complexes is unknown. Here, we perform affinity purification followed by mass spectrometry and demonstrate that the Arabidopsis RPD3-type histone deacetylases HDA6 and HDA19 interact with several previously uncharacterized proteins, thereby forming three types of plant-specific histone deacetylase complexes, which we named SANT, ESANT, and ARID. RNA-seq indicates that the newly identified components function together with HDA6 and HDA19 and coregulate the expression of a number of genes. HDA6 and HDA19 were previously thought to repress gene transcription by histone deacetylation. We find that the histone deacetylase complexes can repress gene expression via both histone deacetylation-dependent and -independent mechanisms. In the mutants of histone deacetylase complexes, the expression of a number of stress-induced genes is up-regulated, and several mutants of the histone deacetylase complexes show severe retardation in growth. Considering that growth retardation is thought to be a trade-off for an increase in stress tolerance, we infer that the histone deacetylase complexes identified in this study prevent overexpression of stress-induced genes and thereby ensure normal growth of plants under nonstress conditions., (Copyright © 2021 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.)

Reversible lysine methylation is essential for regulating histones and emerges to critically regulate non-histone proteins as well. Here we show that the master transcription factor OCT4 in pluripotent stem cells (PSCs) was methylated at multiple lysine residues. LSD1 that is highly expressed in PSCs can directly interact with and demethylate OCT4 at lysine 222 (K222) in the flexible linker region. Reduced LSD1 activity led to the methylation of OCT4-K222 that diminished the differentiation potential of PSCs while facilitating proteasome-independent degradation of OCT4 proteins. Furthermore, site-specifically replacing K222 with phenylalanine to mimic the constitutively methylated lysine promoted the 'locked-in' mode engagement of the OCT4 PORE-homodimers that tightly bind to and block the transcription of multiple PORE-motif-containing target genes regulating cell fate determination and cell junction organization, and thereby reducing the pluripotency of PSCs. Thus, LSD1-mediated demethylation of OCT4 plays a crucial role in restricting the 'locked-in' mode binding of OCT4 PORE-homodimers to the PORE-motif-containing genes and thereby maintaining their transcription to safeguard the pluripotency of PSCs.

Schizophrenia (SZ) is characterized by a series of cognitive impairments, including automatic processing impairment of basic auditory information, indexed by mismatch negativity (MMN). Existing studies mainly focus on MMN induced by deviant of single acoustic features, and relatively few studies have focused on complex acoustic stimuli, especially speech-induced MMN. Many cognitive impairments in SZ are related to speech function. Thus, the present study aimed to examine the reduction of phonetic MMN in SZ as a potential biomarker and its relationship with illness course and functional outcomes. Electroencephalogram (EEG) signals were recorded from 32 SZ and 32 healthy controls (HC) in a double oddball paradigm, with /da/ as the standard stimulus and /ba/ and /du/ as the deviant stimuli. MMN was computed for vowel and consonant deviants separately. Clinical symptoms were assessed using the Positive and Negative Symptom Rating Scale (PANSS). Illness duration and illness relapse were acquired by combining clinical interviews and electronic medical records. Functional outcomes were assessed using the Global Assessment of Functioning scale (GAF). Compared with HC, SZ showed lower amplitudes of phonetic MMN, especially for vowel deviants. In addition, the MMN amplitude of the vowel deviant was significantly correlated with illness duration, illness relapse, and functional outcomes among patients with SZ. These findings indicate that the pre-attentive automatic phonetic processing of SZ was impaired for both consonants and vowels, while the vowel processing deficit may be the key speech processing deficit in SZ, which could depict the illness course and predict the functional outcomes., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Sphingomyelin (SM) is an essential component of biological lipid rafts, and it plays an indispensable role in maintaining plasma membrane stability and in mediating signal transduction. The ultimate biosynthesis of SM is catalyzed by two sphingomyelin synthases (SMSs) namely SMS1 and SMS2, which are selectively distributed in the trans-Golgi apparatus and the plasma membrane. It has been demonstrated that SMS2 acts as an irreplaceable molecule in the regulation of transmembrane signaling, and loss of SMS2 has been reported to worsen atherosclerosis and liver steatosis. However, the function of SMS2 in platelet activation and its association with the pathological process of thrombosis in acute coronary syndrome (ACS) and portal hypertension (PH) remain unclear., Methods: In this study, we tested the role of SMS2 in platelet activation and thrombosis using SMS2 knockout (SMS2 -/-) mice and SMS2-specific inhibitor, D609. Furthermore, we detected SMS2 expression in patients with ACS and PH., Results: SMS2 -/- platelets showed significant reduction in platelet aggregation, spreading, clot retraction and in vivo thrombosis. Similar inhibitory effects on platelet activation were detected in D609-treated wild-type platelets. PLCγ/PI3K/Akt signaling pathway was inhibited in SMS2 -/- platelets and D609-treated wild-type platelets. In addition, we discovered that platelet SMS2 expression was remarkably increased in patients with ACS and PH, compared with healthy subjects., Conclusions: Our study indicates that SMS2 acts as a positive regulator of platelet activation and thrombosis, and provides a theoretical basis for the potential use of D609 in anti-thrombosis treatment.