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Background: This study aims to prioritize genes potentially involved in multifactorial or causal relationships with gout., Methods: Using the Summary Data-based Mendelian Randomization (SMR) approach, this research analyzed expression quantitative trait loci (eQTL) data from blood and renal tissues and genome-wide association study (GWAS) data related to gout. It sought to identify genetic loci potentially involved in gout. Heterogeneity testing was conducted with the HEIDI test, and results were adjusted for the False Discovery Rate (FDR). Blood cis-eQTL data were sourced from the eQTLGen Consortium's summary-level data, and renal tissue data came from the V8 release of the GTEx eQTL summary data. Gout GWAS data was sourced from the FinnGen Documentation of the R10 release., Result: SMR analysis identified 14 gene probes in the eQTLGen blood summary-level data significantly associated with gout. The top five ranked genes are: ENSG00000169231 (labeled THBS3, P SMR = 4.16 × 10 -13 ), ENSG00000231064 (labeled THBS3-AS1, P SMR = 1.88 × 10 -8 ), ENSG00000163463 (labeled KRTCAP2, P SMR = 3.88 × 10 -6 ), ENSG00000172977 (labeled KAT5, P SMR = 1.70 × 10 -5 ), and ENSG00000161395 (labeled PGAP3, P SMR = 3.24 × 10 -5 ). Notably, increased expression of KRTCAP2 and PGAP3 is associated with an increased risk of gout, whereas increased expression of THBS3, THBS3-AS1, and KAT5 is associated with a reduced gout risk. No significant gene associations with gout were observed in renal tissue, likely due to the limited sample size of kidney tissue., Conclusion: Our findings have highlighted several genes potentially involved in the pathogenesis of gout. These results offer valuable insights into the mechanisms of gout and identify potential therapeutic targets for its treatment., 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 © 2024 Wang, Chen, Yao, Li, Xu and Zhang.)

Campanumoea javanica Bl. (CJ) traditionally used in Southwestern China, is now widely consumed as a health food across the nation. Due to its similar efficacy to Codonopsis Radix (CR) and their shared botanical family, CJ is often used as a substitute for CR. According to the Chinese Pharmacopoeia, Codonopsis pilosula var. modesta (Nannf.) L.T. Shen (CPM), Codonopsis pilosula (Franch.) Nannf. (CP), and Codonopsis tangshen Oliv. (CT) are the primary sources of CR. However, details on the differences in composition, effectiveness, and compositional between CJ and CR are still limited. Besides, there is little evidence to support the application of CJ as a drug. In this study, we employed widely targeted metabolomics, network pharmacology analysis, and molecular docking to explore the disparities in metabolite profiles between CJ and CR and to predict the pharmacological mechanisms of the dominant differential metabolites of CJ and their potential medicinal applications. The widely targeted metabolomics results indicated that 1,076, 1,102, 1,102, and 1,093 compounds, most phenolic acids, lipids, amino acids, and flavonoids, were characterized in CJ, CPM, CP, and CT, respectively. There were an average of 1061 shared compounds in CJ and CRs, with 95.07% similarity in metabolic profiles. Most of the metabolites in CJ were previously unreported. Twelve of the seventeen dominant metabolites found in CJ were directly associated with treating cancer and lactation, similar to the traditional medicinal efficacy. The molecular docking results showed that the dominant metabolites of CJ had good docking activity with the core targets PIK3R1, PIK3CA, ESR1, HSP90AA1, EGFR, and AKT1. This study provides a scientific basis for understanding the similarities and differences between CJ and CR at the metabolome level, offering a theoretical foundation for developing innovative medications from CJ. Additionally, it significantly enhances the metabolite databases for both CJ and CR., (© 2024. The Author(s).)

Insects detect and discriminate a diverse array of chemicals using odorant receptors (ORs), which are ligand-gated ion channels comprising a divergent odorant-sensing OR and a conserved odorant receptor co-receptor (Orco). In this work, we report structures of the Ap OR5-Orco heterocomplex from the pea aphid Acyrthosiphon pisum alone and bound to its known activating ligand, geranyl acetate. In these structures, three Ap Orco subunits serve as scaffold components that cannot bind the ligand and remain relatively unchanged. Upon ligand binding, the pore-forming helix S7b of Ap OR5 shifts outward from the central pore axis, causing an asymmetrical pore opening for ion influx. Our study provides insights into odorant recognition and channel gating of the OR-Orco heterocomplex and offers structural resources to support development of innovative insecticides and repellents for pest control.

Objective: The study aims to investigate the relationship between amplitude modulation (AM) of EEG and anesthesia depth during general anesthesia., Methods: In this study, Holo-Hilbert spectrum analysis (HHSA) was used to decompose the multichannel EEG signals of 15 patients to obtain the spatial distribution of AM in the brain. Subsequently, HHSA was applied to the prefrontal EEG (Fp1) obtained during general anesthesia surgery in 15 and 34 patients, and the α-θ and α-δ regions of feature (ROFs) were defined in Holo-Hilbert spectrum (HHS) and three features were derived to quantify AM in ROFs., Results: During anesthetized phase, an anteriorization of the spatial distribution of AMs of α-carrier in brain was observed, as well as AMs of α-θ and α-δ in the EEG of Fp1. The total power ([Formula: see text]), mean carrier frequency ([Formula: see text]) and mean amplitude frequency ([Formula: see text]) of AMs changed during different anesthesia states., Conclusion: HHSA can effectively analyze the cross-frequency coupling of EEG during anesthesia and the AM features may be applied to anesthesia monitoring., Significance: The study provides a new perspective for the characterization of brain states during general anesthesia, which is of great significance for exploring new features of anesthesia monitoring.

Achieving all electrical control of magnetism without assistance of an external magnetic field has been highly pursued for spintronic applications. In recent years, the manipulation of magnetic states through spin-orbit torque (SOT) has emerged as a promising avenue for realizing energy-efficient spintronic memory and logic devices. Here, we provide a review of the rapidly evolving research frontiers in all electrical control of magnetization by SOT. The first part introduces the SOT mechanisms and SOT devices with different configurations. In the second part, the developments in all electrical SOT control of magnetization enabled by spin current engineering are introduced, which include the approaches of lateral symmetry breaking, crystalline structure engineering of spin source material, antiferromagnetic order and interface-generated spin current. The third part introduces all electrical SOT switching enabled by magnetization engineering of the ferromagnet, such as the interface/interlayer exchange coupling and tuning of anisotropy or magnetization. At last, we provide a summary and future perspectives for all electrical control of magnetization by SOT., (© 2024 IOP Publishing Ltd.)

Background: As a therapy to prevent and treat essential hypertension (EH), traditional Chinese exercises (TCEs) were widely used in clinical practice. However, there is a lack of strictly comparison of the antihypertensive efficacy of different TCEs, which not conducive to the selection of the best and most optimal treatment. This study aimed to perform a network meta-analysis to objectively evaluate which TCE has the best effects in assisting with lowering blood pressure., Methods: PubMed, Embase, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), VIP, SinoMed and Wanfang Data were searched for all randomized controlled trials (RCTs) on TCEs for the treatment of EH published up to July 10, 2023. RoB2.0 tool was utilized to evaluate the quality of the RCTs. The network meta-analysis was performed by R 4.1.2 and Stata 17.0. Weighted mean difference (WMD) was calculated for continuous outcomes., Results: A total of 29 studies, including 2,268 patients were included to analyze 6 different interventions. The network meta-analysis results presented that in comparison with control group, Tai Chi + antihypertensive medication [WMD = -10.18, 95% CI, (-14.94, -5.44)] is the most effective intervention for lowering systolic blood pressure (SBP), and Wuqinxi + antihypertensive medication [WMD = -10.36, 95% CI (-18.98, -1.66)] is the most effective intervention for lowering diastolic blood pressure (DBP)., Conclusion: TCEs combined with antihypertensive medication may be able to achieve more prominent antihypertensive effects with Tai Chi and Wuqinxi potentially being the higher-priority options. However, well-designed randomized studies are warranted to further verify currently conclusion., 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., (© 2024 Zhang, Xu, Wu, Zhang, Huang, Wu, Tian and Zhang.)

Although most species have two sexes, multisexual (or multi-mating type) species are also widespread. However, it is unclear how mating-type recognition is achieved at the molecular level in multisexual species. The unicellular ciliate Tetrahymena thermophila has seven mating types, which are determined by the MTA and MTB proteins. In this study, we found that both proteins are essential for cells to send or receive complete mating-type information, and transmission of the mating-type signal requires both proteins to be expressed in the same cell. We found that MTA and MTB form a mating-type recognition complex that localizes to the plasma membrane, but not to the cilia. Stimulation experiments showed that the mating-type-specific regions of MTA and MTB mediate both self- and non-self-recognition, indicating that T. thermophila uses a dual approach to achieve mating-type recognition. Our results suggest that MTA and MTB form an elaborate multifunctional protein complex that can identify cells of both self and non-self mating types in order to inhibit or activate mating, respectively., Competing Interests: GY, YM, YW, JZ, HC, FT, SW, DZ, JX, PY, WM No competing interests declared, (© 2024, Yan et al.)

In plant leaves, starch is composed of glucan polymers that accumulate in chloroplasts as the products of photosynthesis during the day; starch is mobilized at night to continuously provide sugars to sustain plant growth and development. Efficient starch degradation requires the involvement of several enzymes, including β-amylase and glucan phosphatase. However, how these enzymes cooperate remains largely unclear. Here, we show that the glucan phosphatase LIKE SEX FOUR 1 (LSF1) interacts with plastid NAD-dependent malate dehydrogenase (MDH) to recruit β-amylase (BAM1), thus reconstituting the BAM1-LSF1-MDH complex. The starch hydrolysis activity of BAM1 drastically increased in the presence of LSF1-MDH in vitro. We determined the structure of the BAM1-LSF1-MDH complex by a combination of cryo-electron microscopy, crosslinking mass spectrometry, and molecular docking. The starch-binding domain of the dual-specificity phosphatase and carbohydrate-binding module of LSF1 was docked in proximity to BAM1, thus facilitating BAM1 access to and hydrolysis of the polyglucans of starch, thus revealing the molecular mechanism by which the LSF1-MDH complex improves the starch degradation activity of BAM1. Moreover, LSF1 is phosphatase inactive, and the enzymatic activity of MDH was dispensable for starch degradation, suggesting nonenzymatic scaffold functions for LSF1-MDH in starch degradation. These findings provide important insights into the precise regulation of starch degradation., Competing Interests: Conflict of interest statement. None declared., (© American Society of Plant Biologists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: With the internationalization of traditional Chinese medicine, the demand for medicinal and edible Codonopsis Radix (CR) has increased, and its medicinal resources have attracted attention. CR is a well-known traditional Chinese medicine with a long pharmaceutical and edible history. The Guizhou province in China has abundant CR resources, but in the absence of systematic studies on species identification and chemical compositions, the capacity of the capacity of the province to CR resource has not been fully utilized., Methodology: We used plant morphology and DNA barcoding techniques to identify Luodang (LD) and Weidang (WD) species. To investigate the differences in metabolites between LD and WD, as well as three Chinese Pharmacopeia CRs, and to predict pharmacological mechanisms of action for the dominant differential metabolites, we utilized widely targeted metabolomics and network pharmacology. The results also revealed the material basis for the excellent food properties of both LD and WD., Results: The plant traits and DNA barcoding molecular identification results indicated that Luodang and Weidang from Guizhou were Codonopsis tangshen and Codonopsis pilosula , respectively. Widely targeted metabolomics analysis revealed that a total of 1,116 metabolites from 14 categories, including phenolic acids, lipids, flavonoids, were found in five CRs and shared 1,054 (94.4%) metabolites. LD and WD each contained 3 and 10 dominant differential metabolites, respectively, which were primarily flavonoids and amino acids. Amino acids, phenolic acids, and organic acids play important roles in their excellent food attributes. In CR, eight dominant differential metabolites were discovered for the first time, including isoorientin-7-O-(6″-feruloyl) glucoside, N-formyl-L-methionine, and cyclo (Phe-Glu), among others. Network pharmacology analyses showed that, in LD, dominant differential metabolites were closely related to anti-tumor, cardiovascular disease improvement, nervous system protection, and metabolic disease treatment, whereas in WD, they were closely related to nervous system protection and cardiovascular disease improvement., Conclusion: The species of LD and WD were included in the Chinese Pharmacopeia, and their metabolite profiles were remarkably similar to CR from traditional producing areas. Therefore, LD and WD can be used and promoted medicinally as CR, and they have potential value for new drug development. This study enriched the database of CR compounds and provided a reference for quality control, resource development, and new drug development of CR., 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 © 2023 Zhang, Zhang, Yang, Long, Xie, Wang, Yao, Wu and Liu.)

Bacillus thuringiensis (Bt)-secreted crystal (Cry) toxins form oligomeric pores in host cell membranes and are a common element in generating insect-resistant transgenic crops. Although Cry toxin function has been well documented, cellular defences against pore-formation have not been as well developed. Elucidation of the processes underlying this defence, however, could contribute to the development of enhanced Bt crops. Here, we demonstrate that Cry1Ca-mediated downregulation of microRNA-7322-5p (miR-7322-5p), which binds to the 3' untranslated region of p38, negatively regulates the susceptibility of Chilo suppressalis to Cry1Ca. Moreover, Cry1Ca exposure enhanced phosphorylation of Hsp19, and hsp19 downregulation increased susceptibility to Cry1Ca. Further, Hsp19 phosphorylation occurs downstream of p38, and pull-down assays confirmed the interactions between Hsp19 and Cry1Ca, suggesting that activation of Hsp19 by the miR-7322-5p/p38/Hsp19 pathway promotes Cry1Ca sequestration. To assess the efficacy of targeting this pathway in planta, double-stranded RNA (dsRNA) targeting C. suppressalis p38 (dsp38) was introduced into a previously generated cry1Ca-expressing rice line (1CH1-2) to yield a single-copy cry1Ca/dsp38 rice line (p38-rice). Feeding on this rice line triggered a significant reduction in C. suppressalis p38 expression and the line was more resistant to C. suppressalis than 1CH1-2 in both short term (7-day) and continuous feeding bioassays as well as field trials. These findings provide new insights into invertebrate epithelium cellular defences and demonstrate a potential new pyramiding strategy for Bt crops., (© 2023 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Using in situ atomic-resolution scanning transmission electron microscopy, atomic movements and rearrangements associated with diffusive solid to solid phase transformations in the Pt-Sn system are captured to reveal details of the underlying atomistic mechanisms that drive these transformations. In the PtSn 4 to PtSn 2 phase transformation, a periodic superlattice substructure and a unique intermediate structure precede the nucleation and growth of the PtSn 2 phase. At the atomic level, all stages of the transformation are templated by the anisotropic crystal structure of the parent PtSn 4 phase. In the case of the PtSn 2 to Pt 2 Sn 3 transformation, the anisotropy in the structure of product Pt 2 Sn 3 dictates the path of transformation. Analysis of atomic configurations at the transformation front elucidates the diffusion pathways and lattice distortions required for these phase transformations. Comparison of multiple Pt-Sn phase transformations reveals the structural parameters governing solid to solid phase transformations in this technologically interesting intermetallic system.

Contrary to topological insulators, topological semimetals possess a nontrivial chiral anomaly that leads to negative magnetoresistance and are hosts to both conductive bulk states and topological surface states with intriguing transport properties for spintronics. Here, we fabricate highly-ordered metallic Pt 3 Sn and Pt 3 Sn x Fe 1-x thin films via sputtering technology. Systematic angular dependence (both in-plane and out-of-plane) study of magnetoresistance presents surprisingly robust quadratic and linear negative longitudinal magnetoresistance features for Pt 3 Sn and Pt 3 Sn x Fe 1-x , respectively. We attribute the anomalous negative longitudinal magnetoresistance to the type-II Dirac semimetal phase (pristine Pt 3 Sn) and/or the formation of tunable Weyl semimetal phases through symmetry breaking processes, such as magnetic-atom doping, as confirmed by first-principles calculations. Furthermore, Pt 3 Sn and Pt 3 Sn x Fe 1-x show the promising performance for facilitating the development of advanced spin-orbit torque devices. These results extend our understanding of chiral anomaly of topological semimetals and can pave the way for exploring novel topological materials for spintronic devices., (© 2023. The Author(s).)

Microcystinase C (MlrC), one key hydrolase of the microcystinase family, plays an important role in linearized microsystin (L-MC) degradation. However, the three-dimensional structure and structural features of MlrC are still unclear. This study obtained high specific activity and high purity of MlrC by heterologous expression, and revealed that MlrC derived from Sphingomonas sp. ACM-3962 (ACM-MlrC) can degrade linearized products of MC-LR, MC-RR and MC-YR to product 3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic acid (Adda), indicating the degradation function and significance in MC-detoxification. More importantly, this study reported the crystal structure of ACM-MlrC at 2.6 Å resolution for the first time, which provides a basis for further understanding the structural characteristics and functions of MlrC. MlrC had a dual-domain feature, namely N and C terminal domain respectively. The N-terminal domain contained a Glutamate-Aspartate-Histidine-Histidine catalytic quadruplex coordinated with zinc ion in each monomer. The importance of zinc ions and their coordinated residues was analyzed by dialysis and site-directed mutagenesis methods. Moreover, the important influence of the N/C-terminal flexible regions of ACM-MlrC was also analyzed by sequence truncation, and then the higher yield and total activity of variants were obtained, which was beneficial to study the better function and application of MlrC., 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 © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Inorganic polyphosphate (polyP) is an ancient energy metabolite and phosphate store that occurs ubiquitously in all organisms. The vacuolar transporter chaperone (VTC) complex integrates cytosolic polyP synthesis from ATP and polyP membrane translocation into the vacuolar lumen. In yeast and in other eukaryotes, polyP synthesis is regulated by inositol pyrophosphate (PP-InsP) nutrient messengers, directly sensed by the VTC complex. Here, we report the cryo-electron microscopy structure of signal-activated VTC complex at 3.0 Å resolution. Baker's yeast VTC subunits Vtc1, Vtc3, and Vtc4 assemble into a 3:1:1 complex. Fifteen trans-membrane helices form a novel membrane channel enabling the transport of newly synthesized polyP into the vacuolar lumen. PP-InsP binding orients the catalytic polymerase domain at the entrance of the trans-membrane channel, both activating the enzyme and coupling polyP synthesis and membrane translocation. Together with biochemical and cellular studies, our work provides mechanistic insights into the biogenesis of an ancient energy metabolite., (© 2023. The Author(s).)

Background: The integrated information theory (IIT) of consciousness introduces a measure Φ to quantify consciousness in a physical system. Directly related to this, general anesthesia aims to induce reversible and safe loss of consciousness (LOC). We sought to propose an electroencephalogram (EEG)-based IIT index Φ EEG to evaluate various states of consciousness under general anesthesia., Methods: Based on the definition of mutual information, we estimated the Φ EEG by maximizing the integrated information under various time lags. We used the binning method to cut the nonGaussian EEG data for estimating mutual information. We tested two EEG databases collected from propofol- (n=20) and sevoflurane-induced (n=15) anesthesia, and especially, we compared the Φ EEG of drowsy (n=7) and responsive participants (n=13) under propofol anesthesia. We compared the effectiveness of Φ EEG with the estimated bispectral index (eBIS)., Results: In all EEG frequency bands, we observed a negative correlation between Φ EEG and end-tidal sevoflurane concentration under sevoflurane-induced anesthesia (p<0.001,BF 10 >6000). Under propofol-induced anesthesia, drowsy participants in moderate sedation (6.96±0.26(mean±SD)) showed decreased alpha-band Φ EEG compared with baseline (7.40±0.53,p=0.016,BF 10 =3.58), no significant difference was observed for responsive participants. Oppositely, the responsive participants in moderate sedation (-5.32±0.38) showed decreased eBIS compared with baseline (-4.94±0.40,p=0.03,BF 10 =2.41)., Conclusions: These findings may enable monitors of the anesthetic state that can distinguish consciousness and unconsciousness rather than the changes of anesthetic concentrations. The alpha-band Φ EEG is promising for deriving the gold standard for depth of anesthesia monitoring., 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 © 2022 Elsevier Ltd. All rights reserved.)

N 6 -methyldeoxyadenine (6mA) has recently been reported as a prevalent DNA modification in eukaryotes. The Tetrahymena thermophila MTA1 complex consisting of four subunits, namely MTA1, MTA9, p1, and p2, is the first identified eukaryotic 6mA methyltransferase (MTase) complex. Unlike the prokaryotic 6mA MTases which have been biochemically and structurally characterized, the operation mode of the MTA1 complex remains largely elusive. Here, we report the cryogenic electron microscopy structures of the quaternary MTA1 complex in S-adenosyl methionine (SAM)-bound (2.6 Å) and S-adenosyl homocysteine (SAH)-bound (2.8 Å) states. Using an AI-empowered integrative approach based on AlphaFold prediction and chemical cross-linking mass spectrometry, we further modeled a near-complete structure of the quaternary complex. Coupled with biochemical characterization, we revealed that MTA1 serves as the catalytic core, MTA1, MTA9, and p1 likely accommodate the substrate DNA, and p2 may facilitate the stabilization of MTA1. These results together offer insights into the molecular mechanism underpinning methylation by the MTA1 complex and the potential diversification of MTases for N 6 -adenine methylation., (© 2023. The Author(s).)

The plant UV-B photoreceptor UV RESISTANCE LOCUS 8 (UVR8) exists as a homodimer in its inactive ground state. Upon UV-B exposure, UVR8 monomerizes and interacts with a downstream key regulator, the CONSTITUTIVE PHOTOMORPHOGENIC 1/SUPPRESSOR OF PHYA (COP1/SPA) E3 ubiquitin ligase complex, to initiate UV-B signaling. Two WD40 proteins, REPRESSOR OF UV-B PHOTOMORPHOGENESIS 1 (RUP1) and RUP2 directly interact with monomeric UVR8 and facilitate UVR8 ground state reversion, completing the UVR8 photocycle. Here, we reconstituted the RUP-mediated UVR8 redimerization process in vitro and reported the structure of the RUP2-UVR8 W285A complex (2.0 Å). RUP2 and UVR8 W285A formed a heterodimer via two distinct interfaces, designated Interface 1 and 2. The previously characterized Interface 1 is found between the RUP2 WD40 domain and the UVR8 C27 subregion. The newly identified Interface 2 is formed through interactions between the RUP2 WD40 domain and the UVR8 core domain. Disruption of Interface 2 impaired UV-B induced photomorphogenic development in Arabidopsis thaliana. Further biochemical analysis indicated that both interfaces are important for RUP2-UVR8 interactions and RUP2-mediated facilitation of UVR8 redimerization. Our findings suggest that the two-interface-interaction mode is adopted by both RUP2 and COP1 when they interact with UVR8, marking a step forward in understanding the molecular basis that underpins the interactions between UVR8 and its photocycle regulators., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Anesthetic-induced loss of consciousness (LOC) has been studied using functional connectivity (FC) and functional network analysis (FNA), manifested as fragmentation of the whole-brain functional network. However, how the fragmented brain networks reversibly recover during the recovery of consciousness (ROC) remains vague. This study aims to investigate the changes in brain network structure during ROC, to better understand the network fragmentation during anesthesia, thus providing insights into consciousness monitoring. We analyzed EEG data recorded from 15 individuals anesthetized by sevoflurane. By investigating the properties of functional networks generated using different brain atlases and performing community detection for functional networks, we explored the changes in brain network structure to understand how fragmented brain networks recover during the ROC. We observed an overall larger FC magnitude during LOC than in the conscious state. The ROC was accompanied by the increasing binary network efficiency, decreasing FC magnitude, and decreasing community similarity with the functional atlas. Furthermore, we observed a negative correlation between modularity and community number ( [Formula: see text] and , linear regression test), in which modularity increased and community number decreased during ROC. Our results show that a larger FC magnitude reveals excessive synchronization of neuronal activities during LOC. The increasing binary network efficiency, decreasing community number, and decreasing community similarity indicate the recovery of functional network integration. The increasing modularity implies the recovery of functional network segregation during ROC. The results suggest the limitation of FC magnitude and modularity in monitoring anesthetized states and the potential of integrated information theory to evaluate consciousness.

Despite their rapid emergence as the dominant paradigm for electrochemical energy storage, the full promise of lithium-ion batteries is yet to be fully realized, partly because of challenges in adequately resolving common degradation mechanisms. Positive electrodes of Li-ion batteries store ions in interstitial sites based on redox reactions throughout their interior volume. However, variations in the local concentration of inserted Li-ions and inhomogeneous intercalation-induced structural transformations beget substantial stress. Such stress can accumulate and ultimately engender substantial delamination and transgranular/intergranular fracture in typically brittle oxide materials upon continuous electrochemical cycling. This perspective highlights the coupling between electrochemistry, mechanics, and geometry spanning key electrochemical processes: surface reaction, solid-state diffusion, and phase nucleation/transformation in intercalating positive electrodes. In particular, we highlight recent findings on tunable material design parameters that can be used to modulate the kinetics and thermodynamics of intercalation phenomena, spanning the range from atomistic and crystallographic materials design principles (based on alloying, polymorphism, and pre-intercalation) to emergent mesoscale structuring of electrode architectures (through control of crystallite dimensions and geometry, curvature, and external strain). This framework enables intercalation chemistry design principles to be mapped to degradation phenomena based on consideration of mechanics coupling across decades of length scales. Scale-bridging characterization and modeling, along with materials design, holds promise for deciphering mechanistic understanding, modulating multiphysics couplings, and devising actionable strategies to substantially modify intercalation phase diagrams in a manner that unlocks greater useable capacity and enables alleviation of chemo-mechanical degradation mechanisms., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Phase-amplitude coupling (PAC) plays an important role in anesthetic-induced unconsciousness. The delta-alpha PAC signature during anesthetic-induced unconsciousness is gradually becoming known; however, the frequency dependence and spatial characteristics of PAC are still unclear. Multi-channel electroencephalography (EEG) was performed during the loss and recovery phases of consciousness in patients undergoing general anesthesia using sevoflurane. First, a spectral analysis was used to investigate the power change of the different frequency bands in the EEG signals. Second, PAC comodulogram analysis was performed to confirm the frequencies of the PAC phase drivers. Finally, to investigate the spatial characteristics of PAC, a novel PAC network was constructed using within- and cross-lead PAC, and a K-means clustering algorithm was used to identify PAC network patterns. Our results show that, in addition to the delta-alpha PAC, unconsciousness induced by sevoflurane was accompanied by spatial non-uniform alpha-gamma PAC in the cortical network, and dynamic PAC patterns between the anterior and posterior brain were observed during the unconscious phase. The dynamic transition of PAC network patterns indicates that brain states under sevoflurane-induced unconsciousness emerge from the regulation of functional integration and segregation instantiated by delta-alpha and alpha-gamma PAC., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Japan Neuroscience Society and Elsevier Ltd. All rights reserved.)

Cognitive dysfunction after anesthesia and surgery has long been recognized. Recently, researchers provided empirical evidence for social cognition dysfunction (SCD) after anesthesia and surgery. In the present study, we concentrated on the deficits in emotion recognition, one of the most important clinical perspectives in SCD, in patients who underwent cardiac surgery. Biological motion (BM) was considered as the stimulus of interest, and patients' abilities of BM emotion perception and action perception before and after anesthesia and surgery were examined. In total, 60 adult patients (40-72 years old) completed the BM recognition task, which required them to label the types of actions and emotions of perceived BM. The results showed that while action perception remained intact after cardiac surgery, 18.3% of patients exhibited deficits in emotion perception, further confirming the existence of SCD after anesthesia and surgery., 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 Zhang, Shen, Chen, Guo, Gao, Huang and Lu.)

Background: In recent years, gene knockdown technology using double-stranded RNA (dsRNA) has been widely used as an environment-friendly pest control strategy, but its instability and limited cellular uptake have limited its overall effect. Studies have shown that the efficiency of single dsRNA can be improved by using various nanomaterials. However, the effect of stacked-dsRNA wrapped by nanomaterial on pests remains unclear. In the present study, both CYP15C1 and C-factor genes were cloned from the midgut of C. suppressalis, and the transcript of C-factor is most highly expressed in heads. Feeding a dsCYP15C1 or dsC-factor - nanomaterial mixture can downregulate the gene expression and significantly increase larval mortality. More importantly, feeding the stacked-dsRNA wrapped by nanomaterial can significantly increase the mortality of C. suppressalis, compared with feeding dsCYP15C1 or dsC-factor - nanomaterial mixture alone. These results showed that CYP15C1 and C-factor could be potential targets for an effective management of C. suppressalis, and we developed a nanoparticle-facilitated stacked-dsRNA strategy in the control of C. suppresallis. Our research provides a theoretical basis for gene function analysis and field pest control, and will promote the application of RNAi technology in the stacked style of pest control., Competing Interests: Declaration of Competing Interest All authors have confirmed that they have no financial conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

First discovered in the 1980s, retrons are bacterial genetic elements consisting of a reverse transcriptase and a non-coding RNA (ncRNA). Retrons mediate antiphage defence in bacteria but their structure and defence mechanisms are unknown. Here, we investigate the Escherichia coli Ec86 retron and use cryo-electron microscopy to determine the structures of the Ec86 (3.1 Å) and cognate effector-bound Ec86 (2.5 Å) complexes. The Ec86 reverse transcriptase exhibits a characteristic right-hand-like fold consisting of finger, palm and thumb subdomains. Ec86 reverse transcriptase reverse-transcribes part of the ncRNA into satellite, multicopy single-stranded DNA (msDNA, a DNA-RNA hybrid) that we show wraps around the reverse transcriptase electropositive surface. In msDNA, both inverted repeats are present and the 3' sides of the DNA/RNA chains are close to the reverse transcriptase active site. The Ec86 effector adopts a two-lobe fold and directly binds reverse transcriptase and msDNA. These findings offer insights into the structure-function relationship of the retron-effector unit and provide a structural basis for the optimization of retron-based genome editing systems., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Taihu Lake is the most important drinking water source of the major cities in the Yangtze River Delta. The pollution of endocrine disruptors (EDCs)in Taihu Lake has been increasing recently, the accurate determination is an important guide for predicting its health risks and developing appropriate controls. Monitoring organic pollutants in water using the diffusive gradient in thin film technique (DGT) has attracted much attention due to more accuracy and convenience than the grab sampling methods. In this study, a novel cyclodextrin polymer (CDP) synthesized by the simple and green method in water was taken as an adsorbent for the binding gel. Four endocrine-disrupting chemicals (EDCs), bisphenol A (BPA), 17α-ethinylestradiol (EE2), 17β-estradiol (E2), and estriol (E3), were taken as models to determine the diffusion coefficients (4.68 × 10 -6 , 3.38 × 10 -6 , 3.34 × 10 -6 and 4.31 × 10 -6  cm 2 /s) and to test the performance of DGT, such as adsorption capacity and deployment time (1-5 day). The assembled CDP-DGT was adopted to determine four EDCs in a simulated water environment (3-9 of pH, 0.001-0.5 M of ionic strength (IS), and dissolved organic matter (DOM) of 0-20 mg/L). The ability of CDP-DGT sampling was verified in the Jiuxiang River and was carried out for a large-scale field application of in situ sampling EDCs in Taihu Lake basin. The results show that the total EDCs concentration range and the estradiol equivalent concentrations (EEQ) in Taihu Lake and its main rivers are 2.78 ng/L to 11.08 ng/L and 2.62 ng/L to 10.91 ng/L, respectively. The risk quotients (RQs) of all sampling sites in the region were greater than 1, indicating that EDCs pose a serious threat to aquatic organisms in the area. Therefore, the monitoring of EDCs in the Taihu Lake basin should be further strengthened., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Genetically modified plants with insecticidal proteins from Bacillus thuringiensis (Bt) have been successfully utilized to control various kinds of pests in crop production and reduce the abuse of pesticides. However, a limited number of genes are available for the protection of crops from rice planthopper. Recently, Cry78Aa protein from Bt strain C9F1 has been found to have high insecticidal activity against Laodelphax striatellus and Nilaparvata lugens. It is the first reported single-component protein in the world to combat rice planthoppers, making it very promising for use in transgenic crops. The ambiguous mechanism of Cry78Aa functions prevented further engineering or application. Here, we report the crystal structure of Cry78Aa, which consists of two domains: a C-terminal β-pore forming domain belonging to the aerolysin family and an N-terminal trefoil domain resembling the S-type ricin B lectin. Thus, Cry78Aa could represent a distinctive type of β-pore forming toxin. We also found that Cry78Aa binds carbohydrates such as galactose derivatives and is essential for insecticidal activity against Laodelphax striatellus. Our results suggest a mechanism underlying the function of Cry78Aa against rice planthoppers and pave the way to maximizing the usage of the toxin., (© 2022. The Author(s).)

Background: Recent studies have demonstrated that changes in brain information processing during anesthetic-induced loss of consciousness (LOC) might be influenced by phase-amplitude coupling (PAC) in electroencephalogram (EEG). However, most anesthesia research on PAC typically focuses on delta and alpha oscillations. Studies of spatial-frequency characteristics by PAC for EEG may yield additional insights into understanding the impaired information processing under anesthesia unconsciousness and provide potential improvements in anesthesia monitoring., Objective: Considering different frequency bands of EEG represent neural activities on different spatial scales, we hypothesized that functional coupling simultaneously appears in multiple frequency bands and specific brain regions during anesthesia unconsciousness. In this paper, PAC analysis on whole-brain EEG besides delta and alpha oscillations was investigated to understand the influence of multiple cross-frequency coordination coupling on information processing during the loss and recovery of consciousness., Method: EEG data from fifteen patients without cognitive diseases (7 males/8 females, aged 43.8 ± 13.4 years, weighing 63.3 ± 14.9 kilograms) undergoing lower limb surgery and sevoflurane anesthesia was recorded. To investigate the spatial-frequency characteristics of EEG source signals during loss and recovery of consciousness, the time-resolved PAC (tPAC) was calculated to reflect cross-frequency coordination in different frequency bands (delta, theta, alpha, beta, gamma) and different functional regions (Visual, Limbic, Dorsal attention, Ventral attention, Default, Somatomotor, Control, Salience networks). Furthermore, different patterns (peak-max and trough-max) of PAC were examined by constructing phase-amplitude histograms using phase bins to investigate the different information processing during LOC. The multivariate analysis of variance (MANOVA) and trend analysis were used for statistical analysis., Results: Theta-alpha and alpha-beta PAC were observed during sevoflurane-induced LOC, which significantly changed during loss and recovery of consciousness (F 4,70 = 16.553, p < 0.001 for theta-alpha PAC and F 4,70 = 12.446, p < 0.001 for alpha-beta PAC, MANOVA test). Simultaneously, PAC was distributed in specific functional regions, i.e., Visual, Limbic, Default, Somatomotor, etc. Furthermore, peak-max patterns of theta-alpha PAC were observed while alpha-beta PAC showed trough-max patterns and vice versa., Conclusion: Theta-alpha and alpha-beta PAC observed in specific brain regions represent information processing on multiple spatial scales, and the opposite patterns of PAC indicate opposite information processing on multiple spatial scales during LOC. Our study demonstrates the regulation of local-global information processing during sevoflurane-induced LOC. It suggests the utility of evaluating the balance of functional integration and segregation in monitoring anesthetized states., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease. Misfolded Cu, Zn-superoxide dismutase (SOD1) has been linked to both familial and sporadic ALS. SOD1 fibrils formed in vitro share toxic properties with ALS inclusions. Here we produced cytotoxic amyloid fibrils from full-length apo human SOD1 under reducing conditions and determined the atomic structure using cryo-EM. The SOD1 fibril consists of a single protofilament with a left-handed helix. The fibril core exhibits a serpentine fold comprising N-terminal segment (residues 3-55) and C-terminal segment (residues 86-153) with an intrinsic disordered segment. The two segments are zipped up by three salt bridge pairs. By comparison with the structure of apo SOD1 dimer, we propose that eight β-strands (to form a β-barrel) and one α-helix in the subunit of apo SOD1 convert into thirteen β-strands stabilized by five hydrophobic cavities in the SOD1 fibril. Our data provide insights into how SOD1 converts between structurally and functionally distinct states., (© 2022. The Author(s).)

Carbonaceous materials are considered strong candidates as anode materials for sodium-ion batteries (SIBs), which are expected to play an indispensable role in the carbon-neutral era. Herein, novel braided porous carbon fibres (BPCFs) are prepared using the chemical vapour deposition (CVD) method. The BPCFs possess interwoven porous structures and abundant vacancies. The growth mechanism of the BPCFs can be attributed to the polycrystalline transformation of the nanoporous copper catalyst in the early stage of CVD process. Density functional theory calculations suggest that the Na + adsorption energies of the mono-vacancy edges of the BPCFs (-1.22 and -1.09 eV) are lower than that of an ideal graphene layer (-0.68 eV), clarifying in detail the adsorption-dominated sodium storage mechanism. Hence, the BPCFs as an anode material present an outstanding discharge capacity of 401 mAh g -1 at 0.1 A g-1 after 500 cycles. Remarkably, this BPCFs anode, under high-mass-loading of 5 mg cm-2, shows excellent long-term cycling ability with a reversible capacity of 201 mAh g -1 at 10 A g -1 over 1000 cycles. This study provided a novel strategy for the development of high-performance carbonaceous materials for SIBs., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

The CONSTITUTIVE PHOTOMORPHOGENIC 1-SUPPRESSOR OF PHYA-105 (COP1-SPA) complex is a central repressor of photomorphogenesis. This complex acts as an E3 ubiquitin ligase downstream of various light signaling transduced from multiple photoreceptors in plants. How the COP1-SPA activity is regulated by divergent light-signaling pathways remains largely elusive. Here, we reproduced the regulation pathway of COP1-SPA in ultraviolet-B (UV-B) signaling in vitro and determined the cryo-electron microscopy structure of UV-B receptor UVR8 in complex with COP1. The complex formation is mediated by two-interface interactions between UV-B-activated UVR8 and COP1. Both interfaces are essential for the competitive binding of UVR8 against the signaling hub component HY5 to the COP1-SPA complex. We also show that RUP2 dissociates UVR8 from the COP1-SPA4 1-464 -UVR8 complex and facilitates its redimerization. Our results support a UV-B signaling model that the COP1-SPA activity is repressed by UV-B-activated UVR8 and derepressed by RUP2, owing to competitive binding, and provide a framework for studying the regulatory roles of distinct photoreceptors on photomorphogenesis.

Phosphate (Pi) starvation response (PHR) transcription factors play key roles in plant Pi homeostasis maintenance. They are negatively regulated by stand-alone SPX proteins, cellular receptors for inositol pyrophosphate (PP-InsP) nutrient messengers. How PP-InsP-bound SPX interacts with PHRs is poorly understood. Here, we report crystal structures of the rice SPX2/InsP 6 /PHR2 complex and of the PHR2 DNA binding (MYB) domain in complex with target DNA at resolutions of 3.1 Å and 2.7 Å, respectively. In the SPX2/InsP 6 /PHR2 complex, the signalling-active SPX2 assembles into a domain-swapped dimer conformation and binds two copies of PHR2, targeting both its coiled-coil (CC) oligomerisation domain and MYB domain. Our results reveal that the SPX2 senses PP-InsPs to inactivate PHR2 by establishing severe steric clashes with the PHR2 MYB domain, preventing DNA binding, and by disrupting oligomerisation of the PHR2 CC domain, attenuating promoter binding. Our findings rationalize how PP-InsPs activate SPX receptor proteins to target PHR family transcription factors., (© 2022. The Author(s).)

Perpendicular magnetic tunnel junctions (p-MTJs) switched utilizing bipolar electric fields have extensive applications in energy-efficient memory and logic devices. Voltage-controlled magnetic anisotropy linearly lowers the energy barrier of the ferromagnetic layer via the electric field effect and efficiently switches p-MTJs only with a unipolar behavior. Here, we demonstrate a bipolar electric field effect switching of 100 nm p-MTJs with a synthetic antiferromagnetic free layer through voltage-controlled exchange coupling (VCEC). The switching current density, ∼1.1 × 10 5 A/cm 2 , is 1 order of magnitude lower than that of the best-reported spin-transfer torque devices. Theoretical results suggest that the electric field induces a ferromagnetic-antiferromagnetic exchange coupling transition of the synthetic antiferromagnetic free layer and generates a fieldlike interlayer exchange coupling torque, which causes the bidirectional magnetization switching of p-MTJs. These results could eliminate the major obstacle in the development of spin memory devices beyond their embedded applications.

With the internationalization of traditional Chinese medicines (TCMs) and the increasing use of herbal medicines around the world, there are concerns over their safety. In recent years, there have been some sporadic reports of pesticide residues in Chuanxiong Rhizoma (CX), although the lack of systematic and comprehensive analyses of pesticide residues and evaluations of toxicological risks in human health has increased the uncertainty of the potential effects of pesticides exposure in humans. This study aimed to clarify the status of pesticide residues and to determine the health risks of pesticide residues in CX. The findings of this study revealed that 99 batches of CX samples contained pesticide residues ranging from 0.05 to 3013.17 μg/kg. Here, 6-22 kinds of pesticides were detected in each sample. Prometryn, carbendazim, dimethomorph, chlorpyrifos, chlorantraniliprole, pyraclostrobin, and paclobutrazol were the most frequently detected pesticides, with detection rates of 68.69-100%. Insecticides and fungicides accounted for 43.23% and 37.84% of the total pesticides detected, respectively. Here, 86.87% of the pesticide content levels were lower than 50 μg/kg, and a small number of samples contained carbofuran, dimethoate, and isofenphos-methyl exceeding the maximum residue levels (MRLs). A risk assessment based on the hazard quotient/hazard index (HQ/HI) approach revealed that the short-term, long-term, and cumulative risks of pesticide residues in CX are well below the levels that may pose a health risk. Worryingly, six banned pesticides (carbofuran, phorate sulfone, phorate-sulfoxide, isofenphos-methyl, terbufos-sulfone, and terbufoxon sulfoxide) were detected. This study has improved our understanding of the potential exposure risk of pesticide multi-residues in CX. The results of the study will have a positive impact on improving the quality and safety of CX and the development of MRLs for pesticide residues.

Various kinds of cap structures, such as m 7 G, triphosphate groups, NAD and dpCoA, protect the 5' terminus of RNA. The cap structures bond covalently to RNA and affect its stability, translation, and transport. The removal of the caps is mainly executed by Nudix hydrolase family proteins, including Dcp2, RppH and NudC. Numerous efforts have been made to elucidate the mechanism underlying the removal of m 7 G, triphosphate group, and NAD caps. In contrast, few studies related to the cleavage of the RNA dpCoA cap have been conducted. Here, we report the hydrolytic activity of Escherichia coli NudC towards dpCoA and dpCoA-capped RNA in vitro . We also determined the crystal structure of dimeric NudC in complex with dpCoA at 2.0 Å resolution. Structural analysis revealed that dpCoA is recognized and hydrolysed in a manner similar to NAD. In addition, NudC may also remove other dinucleotide derivative caps of RNA, which comprise the AMP moieties. NudC homologs in Saccharomyces cerevisiae and Arabidopsis thaliana exhibited similar dpCoA decapping (deCoAping) activity. These results together indicate a conserved mechanism underpinning the hydrolysis of dpCoA-capped RNA in both prokaryotes and eukaryotes.

β barrel outer membrane proteins (β-OMPs) play vital roles in mitochondria, chloroplasts, and Gram-negative bacteria. Evolutionarily conserved complexes such as the mitochondrial sorting and assembly machinery (SAM) mediate the assembly of β-OMPs. We investigated the SAM-mediated assembly of the translocase of the outer membrane (TOM) core complex. Cryo–electron microscopy structures of SAM–fully folded Tom40 and the SAM-Tom40/Tom5/Tom6 complexes at ~3-angstrom resolution reveal that Sam37 stabilizes the mature Tom40 mainly through electrostatic interactions, thus facilitating subsequent TOM assembly. These results support the β barrel switching model and provide structural insights into the assembly and release of β barrel complexes.

Prion diseases are caused by the conformational conversion of prion protein (PrP). Forty-two different mutations were identified in human PrP, leading to genetic prion diseases with distinct clinical syndromes. Here, we report the cryo–electron microscopy structure of an amyloid fibril formed by full-length human PrP with E196K mutation, a genetic Creutzfeldt-Jakob disease–related mutation. This mutation disrupts key interactions in the wild-type PrP fibril, forming an amyloid fibril with a conformation distinct from the wild-type PrP fibril and hamster brain–derived prion fibril. The E196K fibril consists of two protofibrils. Each subunit forms five β strands stabilized by a disulfide bond and an unusual hydrophilic cavity stabilized by a salt bridge. Four pairs of amino acids from opposing subunits form four salt bridges to stabilize the zigzag interface of the two protofibrils. Our results provide structural evidences of the diverse prion strains and highlight the importance of familial mutations in inducing different strains.

Voltage control of magnetic order is desirable for spintronic device applications, but 180° magnetization switching is not straightforward because electric fields do not break time-reversal symmetry. Ferrimagnets are promising candidates for 180° switching owing to a multi-sublattice configuration with opposing magnetic moments of different magnitudes. In this study we used solid-state hydrogen gating to control the ferrimagnetic order in rare earth-transition metal thin films dynamically. Electric field-induced hydrogen loading/unloading in GdCo can shift the magnetic compensation temperature by more than 100 K, which enables control of the dominant magnetic sublattice. X-ray magnetic circular dichroism measurements and ab initio calculations indicate that the magnetization control originates from the weakening of antiferromagnetic exchange coupling that reduces the magnetization of Gd more than that of Co upon hydrogenation. We observed reversible, gate voltage-induced net magnetization switching and full 180° Néel vector reversal in the absence of external magnetic fields. Furthermore, we generated ferrimagnetic spin textures, such as chiral domain walls and skyrmions, in racetrack devices through hydrogen gating. With gating times as short as 50 μs and endurance of more than 10,000 cycles, our method provides a powerful means to tune ferrimagnetic spin textures and dynamics, with broad applicability in the rapidly emerging field of ferrimagnetic spintronics., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Figure 1 is updated due to the mistake that occurred during the layout process. Reference: Aiqing Nie, Yueyue Xiao, Si Liu, Xiaolei Zhu, Delin Zhang. Sensitivity of Reality Monitoring to Fluency: Evidence from Behavioral Performance and Event-Related Potential (ERP) Old/New Effects. Med Sci Monit. 2019; 25: 9490-9498. 10.12659/MSM.917401.

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.)

Background: This study aimed to evaluate the timing of laparoscopic cholecystectomy (LC) after percutaneous transhepatic gallbladder drainage (PTGBD)., Methods: Patients with acute moderate to severe cholecystitis treated by LC after PTGBD in the Department of Hepatobiliary and Pancreatic Surgery, Nankai Hospital (N-362) between January 2017 and August 2019were retrospectively enrolled into this study. According to the interval times from PTGBD to LC, the patients were divided into six groups, including group A (105 cases, within 1 week), group B (62 cases, 1-2 weeks), group C (34 cases, 3-4 weeks), group D (54 cases, 5-8 weeks), group E (24 cases, 9-12 weeks), and group F (83 cases, over 12 weeks). The gender, age, hospital stay, duration of operation, rate of conversion to laparotomy, incidence of complications, and hospitalization expenses of the six groups were evaluated and compared., Results: Of the 362 cases of LC, 346 patients were operated successfully (95.6%), 10 were converted to laparotomy (2.8%), 16 had various complications (4.4%), and 2 died (0.6%). There were no significant differences between groups in the gender ratio, complication rate, and rate of conversion to laparotomy. The hospital stay and hospitalization expenses in group A were the least and significantly lower than those in other groups (P<0.01), and the duration of operation in group D was the longest and significantly higher than that in groups A, B, E, and F (P<0.05)., Conclusions: For non-elderly patients diagnosed with acute moderate to severe cholecystitis with an anesthesia risk score [American Society of Anesthesiologists (ASA)] ≤2, LC is recommended to be performed within 1 week after PTGBD surgery. If delayed LC is performed within 2 to 8 weeks after PTGBD, the operation time will be longer due to inflammatory edema and fibrous adhesion of the gallbladder triangle. If PTGBD is performed for more than 2 months and the clinical circumstances are good, delayed LC can be considered to reduce the inconvenience of patients with a long-term catheter as much as possible.

The mechanism that coordinates cell growth and cell cycle progression remains poorly understood; in particular, whether the cell cycle and cell wall biosynthesis are coordinated remains unclear. Recently, cell wall biosynthesis and cell cycle progression were reported to respond to wounding. Nonetheless, no genes are reported to synchronize the biosynthesis of the cell wall and the cell cycle. Here, we report that wounding induces the expression of genes associated with cell wall biosynthesis and the cell cycle, and that two genes, AtMYB46 in Arabidopsis thaliana and RrMYB18 in Rosa rugosa, are induced by wounding. We found that AtMYB46 and RrMYB18 promote the biosynthesis of the cell wall by upregulating the expression of cell wall-associated genes, and that both of them also upregulate the expression of a battery of genes associated with cell cycle progression. Ultimately, this response leads to the development of curled leaves of reduced size. We also found that the coordination of cell wall biosynthesis and cell cycle progression by AtMYB46 and RrMYB18 is evolutionarily conservative in multiple species. In accordance with wounding promoting cell regeneration by regulating the cell cycle, these findings also provide novel insight into the coordination between cell growth and cell cycle progression and a method for producing miniature plants., (© 2021 Society for Experimental Biology and John Wiley & Sons Ltd.)

The blue-light receptor cryptochrome (CRY) in plants undergoes oligomerization to transduce blue-light signals after irradiation, but the corresponding molecular mechanism remains poorly understood. Here, we report the cryogenic electron microscopy structure of a blue-light-activated CRY2 tetramer at a resolution of 3.1 Å, which shows how the CRY2 tetramer assembles. Our study provides insights into blue-light-mediated activation of CRY2 and a theoretical basis for developing regulators of CRYs for optogenetic manipulation.

Self-shaping hydrogel actuators have promising applications in various fields. However, one hydrogel actuator can generally access only one specifically predefined deformation and output force, which are determined by its thermodynamic equilibrium swelling state under external stimuli. Here, we present a simple yet versatile strategy for precisely programming the output force/energy of dual-gradient hydrogel actuators. The strategy is based on thermodynamic nonequilibrium snapping deformations occurring during the recovery process of predeformed dual-gradient hydrogel actuators in low-temperature water. The output force/energy of such thermodynamic nonequilibrium snapping deformation is highly associated with predeformation conditions of the hydrogel actuators, which increases with the increase of the predeformation temperature or time. In consequence, just by adjusting the predeformation conditions of the dual-gradient hydrogel actuators, their output force, energy, and power can be modulated precisely and continuously during the snapping deformation. The as-prepared hydrogel actuators can not only be used as smart lifters and grippers with ultrahigh accuracy of weight identification but also act as smart switches in the timing circuits with precisely adjustable operating time, paving the way for the design of a new generation of actuation materials.

Extensive studies have revealed that cognitive processing was impaired after anesthesia and surgery, particularly for the elderly patients. However, most of the existing studies focused on the general cognitive deficits (e.g., delayed neuro-cognitive recovery and POCD). Although diagnosis of social abilities has been used in various clinical fields, few studies have investigated the potential deficit on social cognition after anesthesia and surgery. The current study examined whether there was any social cognitive dysfunction after anesthesia and surgery. We achieved this by taking biological motion (BM) as the stimuli of interest, the perception of which has been taken as the hallmark of social cognition. The elderly patients (aged ≥ 60 years) were required to judge whether an upright BM stimulus appeared among the dynamic noises to test their social cognition, as well as do a Mini-Mental State Examination to test their general cognition. The two tests were performed at both 1-day before and 7-day after the surgery. Results showed that 31.25% of patients exhibited BM perception deficit after anesthesia and surgery relative to before anesthesia and surgery, implying that social cognitive dysfunction existed. Meanwhile, social cognitive dysfunction was independent from delayed neurocognitive recovery., (Copyright © 2020 Zhang, Ying, Ma, Gao, Chen, Zhu, Shi and Lu.)

MS5 is a meiosis-related protein belonging to the Brassicaceae-specific domain of unknown function family and characterized by the MS5 superfamily domain (MSD). In this study, we elucidated the three-dimensional crystal structure and potential biochemical function of the MSD. It was observed that the MSD adopts a cystatin-like fold, mainly consisting of a central α-helix and four- or five-stranded antiparallel β-sheets that wrap around it. However, unlike cystatins, which inhibit cysteine proteases, the MSD displayed allosteric activation of papain. We believe that our study provides insight into novel mechanisms of proteolytic enzyme regulation and may serve as a basis for functional studies of the MS5 family proteins in plants., (© 2020 Federation of European Biochemical Societies.)

Prion diseases are caused by the misfolding of prion protein (PrP). Misfolded PrP forms protease-resistant aggregates in vivo (PrP Sc ) that are able to template the conversion of the native form of the protein (PrP C ), a property shared by in vitro-produced PrP fibrils. Here we produced amyloid fibrils in vitro from recombinant, full-length human PrP C (residues 23-231) and determined their structure using cryo-EM, building a model for the fibril core comprising residues 170-229. The PrP fibril consists of two protofibrils intertwined in a left-handed helix. Lys194 and Glu196 from opposing subunits form salt bridges, creating a hydrophilic cavity at the interface of the two protofibrils. By comparison with the structure of PrP C , we propose that two α-helices in the C-terminal domain of PrP C are converted into β-strands stabilized by a disulfide bond in the PrP fibril. Our data suggest that different PrP mutations may play distinct roles in modulating the conformational conversion.