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Background: Acute lumbar sprain (ALS) is common musculoskeletal disorder characterized by severe low back pain and activity limitation, which significantly impacts the patient's work and life. Immediate relief of pain and restoration of mobility in a short period of time are the main needs of patients when they visit the clinic. This study aims to evaluate the immediate efficacy of this combined treatment for ALS within 10 minutes., Methods: This is a single-center, prospective, randomized clinical trial. 128 eligible patients with ALS will be randomly allocated in a 1:1 ratio to either the auricular acupuncture (AA) group or the sham auricular acupuncture (SAA) group. All patients will receive a single 10-minute treatment. The primary outcome will be the change in pain intensity after 10 minutes of treatment. The secondary outcomes include changes in pain intensity at other time points (2, 5 minutes), changes in lumbar range of motion (ROM) at different time points, blinded assessment, treatment effect expectancy scale evaluation, and treatment satisfaction scale evaluation. All participants will be included in the analysis according to the intention-to-treat principle., Discussion: This is the first randomized controlled trial to assess the immediate efficacy of AA combined with active exercise for ALS. The findings of this study are expected to provide a simple and rapid treatment for ALS in clinical., Trial Registration: Chinese Clinical Trial Registry ChiCTR2400083740. Registered 30 April 2024., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Tang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Van der Waals heterostructures based on transition metal dichalcogenides (TMDs) have emerged as excellent candidates for next-generation optoelectronics and valleytronics, due to their fascinating physical properties. The understanding and active control of the relaxation dynamics of heterostructures play a crucial role in device design and optimization. Here, we investigate the back-gate modulation of exciton dynamics in a WS 2 /WSe 2 heterostructure by combining time-resolved photoluminescence (TRPL) and transient absorption spectroscopy (TAS) at cryogenic temperatures. We find that the non-radiative relaxation lifetimes of photocarriers in heterostructures can be electrically controlled for samples with different twist-angles, whereas such lifetime tuning is not present in standalone monolayers. We attribute such an observation to doping-controlled competition between interlayer and intralayer recombination pathways in high-quality WS 2 /WSe 2 samples. The simultaneous measurement of TRPL and TAS lifetimes within the same sample provides additional insight into the influence of coexisting excitons and background carriers on the photo-response, and points to the potential of tailoring light-matter interactions in TMD heterostructures.

Purpose: Acute lumbar sprain (ALS) is a common clinical disease characterized by persistent intolerable low back pain and limitation of movement, and quick pain relief and restoration of mobility in a short time are the main needs of patients when they visit the clinic. This study aims to evaluate the immediate efficacy of contralateral acupuncture (CAT) on SI3 combined with active exercise in treating ALS., Methods and Analysis: This study is a randomized controlled trial which will recruit 118 eligible participants aged 18 to 55 years with ALS at the Second Affiliated Hospital of Yunnan University of Chinese Medicine between March 2024 and December 2026. Participants will be randomly assigned to the acupuncture group or the sham-acupuncture group in a 1:1 ratio. The acupuncture group will receive a 10-minute acupuncture treatment combined with active exercise, while the sham-acupuncture group will receive a 10-minute sham acupuncture treatment combined with active exercise. Randomization will use a computer-generated sequence with allocation concealed in opaque envelopes. The primary outcome will be the pain visual analogue scale (VAS) scores after 10 minutes of treatment. Secondary outcomes will include the pain VAS scores at other time points (2, 4, 6, and 8 minutes post-treatment), the lumbar range of motion (ROM) scores at various time points, blinded assessment, the treatment effect expectancy scale, and the rescue analgesia rate. The analysis will follow the intention-to-treat principle. The primary outcome will be analyzed using ANCOVA, and secondary outcomes with repeated measures ANOVA. The rescue analgesia rate will be assessed using either the χ 2 test or Fisher's exact test., Discussion: This study is the first randomized controlled trial to assess the immediate efficacy of CAT in combination with active exercise for ALS. This study will provide a simple, rapid, and effective treatment for the clinical management of ALS., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Tang et al.)

Background: The NAC TF family is widely involved in plant responses to various types of stress. Red clover (Trifolium pratense) is a high-quality legume, and the study of NAC genes in red clover has not been comprehensive. The aim of this study was to analyze the NAC gene family of red clover at the whole-genome level and explore its potential role in the Pb stress response., Results: In this study, 72 TpNAC genes were identified from red clover; collinearity analysis showed that there were 5 pairs of large fragment replicators of TpNAC genes, and red clover was found to be closely related to Medicago truncatula. Interestingly, the TpNAC genes have more homologs in Arabidopsis thaliana than in soybean (Glycine max). There are many elements in the TpNAC genes promoters that respond to stress. Gene expression analysis showed that all the TpNAC genes responded to Pb stress. qRT-PCR showed that the expression levels of TpNAC29 and TpNAC42 were significantly decreased after Pb stress. Protein interaction network analysis showed that 21 TpNACs and 23 other genes participated in the interaction. In addition, the TpNAC proteins had three possible 3D structures, and the secondary structure of these proteins were mainly of other types. These results indicated that most TpNAC members were involved in the regulation of Pb stress in red clover., Conclusion: These results suggest that most TpNAC members are involved in the regulation of Pb stress in red clover. TpNAC members play an important role in the response of red clover to Pb stress., (© 2024. The Author(s).)

It is hard to achieve robustness in anaerobic biodegradation of trichlorophenol (TCP). We hypothesized that specific combinations of environmental factors determine phylogenetic diversity and play important roles in the decomposition and stability of TCP-biodegrading bacteria. The anaerobic bioreactor was operated at 35 °C (H condition) or 30 °C (L condition) and mainly fed with TCP (from 28 μM to 180 μM) and organic material. Metagenome sequencing was combined with 16S rRNA gene amplicon sequencing for the microbial community analysis. The results exhibited that the property of robustness occurred in specific conditions. The corresponding co-occurrence and diversity patterns suggest high collectivization, degree and evenness for robust communities. Two types of core functional taxa were recognized: dechlorinators (unclassified Anaerolineae, Thermanaerothrix and Desulfovibrio) and ring-opening members (unclassified Proteobacteria, Methanosarcina, Methanoperedens, and Rubrobacter). The deterministic process of the expansion of niche of syntrophic bacteria at higher temperatures was confirmed. The reductive and hydrolytic dechlorination mechanisms jointly lead to C-Cl bond cleavage. H ultimately adapted to the stress of high TCP loading, with more abundant ring-opening enzyme (EC 3.1.1.45, ∼55%) and hydrolytic dechlorinase (EC 3.8.1.5, 26.5%) genes than L (∼47%, 10.5%). The functional structure (based on KEGG) in H was highly stable despite the high loading of TCP (up to 60 μM), but not in L. Furthermore, an unknown taxon with multiple functions (dechlorinating and ring-opening) was found based on genetic sequencing; its functional contribution of EC 3.8.1.5 in H (26.5%) was higher than that in L (10.5%), and it possessed a new metabolic pathway for biodegradation of halogenated aromatic compounds. This new finding is supplementary to the robust mechanisms underlying organic chlorine biodegradation, which can be used to support the engineering, regulation, and design of synthetic microbiomes., 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. Published by Elsevier Inc.)

Trifolium repens L. (T. repens) is considered a potential phytoremediation species due to its large biomass and ability to accumulate and tolerate heavy metals. Lead (Pb) is an important heavy metal pollutant that can affect plant growth, photosynthesis, and enzyme activity. However, response mechanism of microorganisms in three root niches of metal tolerant plants to Pb is not completely understood. Therefore, in this study, a Pb poisoning model of T. repens was established with a Pb gradient (0, 1000 mg/kg, 2000 mg/kg, and 3000 mg/kg), and was used to evaluate growth and physiological responses, as well as enrichment and transport coefficients in T. repens, and explore the characteristics of rhizosphere soil and microbial composition of three root niches. We found that Pb stress caused oxidative injury, and inhibited photosynthesis in T. repens. 16S rDNA sequencing analysis showed that the richness of microbial communities in bulk soil was higher than that in rhizosphere soil both under Pb stress and Pb nonstress conditions. Moreover, Proteobacteria was dominant phylum in bulk and rhizosphere soils, and Proteobacteria and Cyanobacteria were dominant phylum in endophytic bacteria. For the first time, we systematically investigated the response of Pb from bulk soil to plant leaves. The results showed that microbial interaction existed between bulk and rhizosphere soil. Rhizosphere bacterium Haliangium was positively correlated with urease activity and soil nutrients. Endophytic bacterium Pseudomonas was positively correlated with plant biomass and played an important role in Pb tolerance of T. repens. In addition, endophytic bacteria formed complex correlation networks with growth and physiological indexes of both root and shoot, moreover the network in root was more complicated. Taken together, Pb stress dose-dependently inhibited the growth of plants. This study provided a theoretical basis for the further development of microbial cooperation with plant remediation of heavy metal contaminated soil., 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 Elsevier B.V. All rights reserved.)

N 6 -methyladenosine (m 6 A) is the most abundant eukaryotic mRNA modification and is involved in various biological processes. Increasing evidence has implicated that m 6 A modification is an important anti-viral defense mechanism in mammals and plants, but it is largely unknown how m 6 A regulates viral infection in plants. Here we report the dynamic changes and functional anatomy of m 6 A in Nicotiana benthamiana and Solanum lycopersicum during Pepino mosaic virus (PepMV) infection. m 6 A modification in the PepMV RNA genome is conserved in these two species. Overexpression of the m 6 A writers, mRNA adenosine methylase A (MTA), and HAKAI inhibit the PepMV RNA accumulation accompanied by increased viral m 6 A modifications, whereas deficiency of these writers decreases the viral RNA m 6 A levels but enhances virus infection. Further study reveals that the cytoplasmic YTH-domain family protein NbECT2A/2B/2C as m 6 A readers are involved in anti-viral immunity. Protein-protein interactions indicate that NbECT2A/2B/2C interact with nonsense-mediated mRNA decay (NMD)-related proteins, including NbUPF3 and NbSMG7, but not with NbUPF1. m 6 A modification-mediated restriction to PepMV infection is dependent on NMD-related factors. These findings provide new insights into the functionality of m 6 A anti-viral activity and reveal a distinct immune response that NMD factors recognize the m 6 A readers-viral m 6 A RNA complex for viral RNA degradation to limit virus infection in plants., (© 2023. Science China Press.)

Positive-sense single-stranded RNA (+ssRNA) viruses, the most abundant viruses of eukaryotes in nature, require the synthesis of negative-sense RNA (-RNA) using their genomic (positive-sense) RNA (+RNA) as a template for replication. Based on current evidence, viral proteins are translated via viral +RNAs, whereas -RNA is considered to be a viral replication intermediate without coding capacity. Here, we report that plant and animal +ssRNA viruses contain small open reading frames (ORFs) in their -RNA (reverse ORFs [rORFs]). Using turnip mosaic virus (TuMV) as a model for plant +ssRNA viruses, we demonstrate that small proteins encoded by rORFs display specific subcellular localizations, and confirm the presence of rORF2 in infected cells through mass spectrometry analysis. The protein encoded by TuMV rORF2 forms punctuate granules that are localized in the perinuclear region and co-localized with viral replication complexes. The rORF2 protein can directly interact with the viral RNA-dependent RNA polymerase, and mutation of rORF2 completely abolishes virus infection, whereas ectopic expression of rORF2 rescues the mutant virus. Furthermore, we show that several rORFs in the -RNA of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have the ability to suppress type I interferon production and facilitate the infection of vesicular stomatitis virus. In addition, we provide evidence that TuMV might utilize internal ribosome entry sites to translate these small rORFs. Taken together, these findings indicate that the -RNA of +ssRNA viruses can also have the coding capacity and that small proteins encoded therein play critical roles in viral infection, revealing a viral proteome larger than previously thought., (Copyright © 2023 The Author. Published by Elsevier Inc. All rights reserved.)

Caucasian clover ( Trifolium ambiguum M. Bieb.) is an excellent perennial plant in the legume family Fabaceae, with a well-developed rhizome and strong clonal growth. Auxin is one of the most important phytohormones in plants and plays an important role in plant growth and development. Auxin response factor (ARF) can regulate the expression of auxin-responsive genes, thus participating in multiple pathways of auxin transduction signaling in a synergistic manner. No genomic database has been established for Caucasian clover. In this study, 71 TaARF genes were identified through a transcriptomic database of Caucasian clover rhizome development. Phylogenetic analysis grouped the TaARFs into six (1-6) clades. Thirty TaARFs contained a complete ARF structure, including three relatively conserved regions. Physical and chemical property analysis revealed that TaARFs are unstable and hydrophilic proteins. We also analyzed the expression pattern of TaARFs in different tissues (taproot, horizontal rhizome, swelling of taproot, rhizome bud and rhizome bud tip). Quantitative real-time RT-PCR revealed that all TaARFs were responsive to phytohormones (indole-3-acetic acid, gibberellic acid, abscisic acid and methyl jasmonate) in roots, stems and leaves. These results helped elucidate the role of ARFs in responses to different hormone treatments in Caucasian clover.

Background: The impact of regional anesthesia and analgesia (RAA) on long-term survival following cancer surgery is a topic of debate. The aim of this study was to investigate the effects of perioperative RAA on long-term oncological outcomes in patients undergoing major abdominal cancer surgery., Methods: The authors searched computerized databases and reference lists from inception to December 20, 2022. All studies that investigated the effects of perioperative RAA on long-term oncological outcomes following major abdominal cancer surgery were included. Using the inverse variance method with a random-effects model, hazard ratios (HR) and 95% confidence intervals (CI) were calculated., Results: The systematic review included 51 retrospective studies, one prospective study, and three randomized controlled trials (RCTs), with a total of 95,046 patients. The results showed that perioperative RAA may improve long-term overall survival (HR: 0.85, 95% CI: 0.80 to 0.91, P = 0.00, I 2  = 60.2%). However, there was no significant association between perioperative RAA and reduced cancer recurrence (HR: 0.98, 95% CI: 0.90 to 1.03, P = 0.31, I 2  = 52.3%). When performing a pooled analysis of the data from the three RCTs, no statistically significant effect of RAA was found in either case., Conclusion: The systematic review suggests perioperative RAA may improve long-term overall survival but does not appear to reduce cancer recurrence in patients undergoing major abdominal cancer surgery. The limited number of RCTs included in this study did not confirm this finding, highlighting the need for further RCTs to corroborate these results., Competing Interests: 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., (© 2023 The Authors. Published by Elsevier Ltd.)

Movement proteins (MPs) encoded by plant viruses deliver viral genomes to plasmodesmata (PD) to ensure intracellular and intercellular transport. However, how the MPs encoded by monopartite geminiviruses are targeted to PD is obscure. Here, we demonstrate that the C5 protein of tomato yellow leaf curl virus (TYLCV) anchors to PD during the viral infection following trafficking from the nucleus along microfilaments in Nicotiana benthamiana. C5 could move between cells and partially complement the traffic of a movement-deficient turnip mosaic virus (TuMV) mutant (TuMV-GFP-P3N-PIPO-m1) into adjacent cells. The TYLCV-C5 null mutant (TYLCV-mC5) attenuates viral pathogenicity and decreases viral DNA and protein accumulation, and ectopic overexpression of C5 enhances viral DNA accumulation. Interaction assays between TYLCV-C5 and the other eight viral proteins described in TYLCV reveal that C5 associates with C2 in the nucleus and with V2 in the cytoplasm and at PD. The V2 protein is mainly localized in the nucleus and cytoplasmic granules when expressed alone; in contrast, V2 forms small punctate granules at PD when co-expressed with C5 or in TYLCV-infected cells. The interaction of V2 and C5 also facilitates their nuclear export. Furthermore, C5-mediated PD localization of V2 is conserved in two other geminiviruses. Therefore, this study solves a long-sought-after functional connection between PD and the geminivirus movement and improves our understanding of geminivirus-encoded MPs and their potential cellular and molecular mechanisms., Competing Interests: Conflict of interest statement. The authors declare no conflict of interests., (© American Society of Plant Biologists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Tomato yellow leaf curl virus (TYLCV) is a monopartite geminivirus, and one of the most devastating plant viruses in the world. TYLCV is traditionally known to encode six viral proteins in bidirectional and partially overlapping open reading frames (ORFs). However, recent studies have shown that TYLCV encodes additional small proteins with specific subcellular localizations and potential virulence functions. Here, a novel protein named C7, encoded by a newly-described ORF in the complementary strand, was identified as part of the TYLCV proteome using mass spectrometry. The C7 protein localized to the nucleus and cytoplasm, both in the absence and presence of the virus. C7 was found to interact with two other TYLCV-encoded proteins: with C2 in the nucleus, and with V2 in the cytoplasm, forming conspicuous granules. Mutation of C7 start codon ATG to ACG to block the translation of C7 delayed the onset of viral infection, and the mutant virus caused milder virus symptoms and less accumulations of viral DNAs and proteins. Using the potato virus X (PVX)-based recombinant vector, we found that ectopic overexpression of C7 resulted in more severe mosaic symptoms and promoted a higher accumulation of PVX-encoded coat protein in the late virus infection stage. In addition, C7 was also found to inhibit GFP-induced RNA silencing moderately. This study demonstrates that the novel C7 protein encoded by TYLCV is a pathogenicity factor and a weak RNA silencing suppressor, and that it plays a critical role during TYLCV infection., 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 Elsevier Inc. All rights reserved.)

Combination therapy with antipsychotics has been investigated for treating schizophrenia, and has shown clear advantages among non-invasive therapies. Transcutaneous electrical acupoint stimulation (TEAS) is a novel non-invasive treatment with definite efficacy in treating mental disorders. The current study aimed to investigate the efficacy of TEAS in further improving the psychotic symptoms in patients with first-episode schizophrenia (FES) being treated with pharmacological drugs. This 8-week, preliminary, sham-controlled, randomized clinical trial was conducted in patients with FES to compare the efficacy of TEAS and sham TEAS in combination with aripiprazole treatment. The primary outcome was a change in the Positive and Negative Syndrome Scale (PANSS) score after ending the intervention (Week 8). A total of 49 participants completed the whole treatment cycle. The linear mixed-effects regression for PANSS indicated a significant time × group interaction (F(2, 116)=9.79, p <0.001). The PANSS score differed by 8.77 points (95% CI, -2.07 to -15.47 points; p=.01) between the TEAS group and the sham TEAS group after 8 weeks of treatment; this difference was significant. This study indicates that 8 weeks of TEAS combined with aripiprazole treatment can effectively treat FES. Thus, TEAS is an effective combination therapy to improve the psychiatric symptoms of FES., Competing Interests: Declaration of Competing Interest The authors of this manuscript declare that they have no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Designing an active, stable, and nonprecious metal catalyst substitute for Pt in the oxygen reduction reaction (ORR) is highly demanded for energy-efficient and cost-effective prototype devices. Single-atomic-site catalysts (SASCs) have been widely concerning because of their maximum atomic utilization and precise structural regulation. Despite being challenging, the controllable synthesis of SASCs is crucial for optimizing ORR activity. Here, we demonstrate an ultrathin organometallic framework template-assisted pyrolysis strategy to synthesize SASCs with a unique two-dimensional (2D) architecture. Electrochemical measurements revealed that Fe-SASCs displayed an excellent ORR activity in an alkaline media, having a half-wave potential and a diffusion-limited current density comparable to those of commercial Pt/C. Remarkably, the durability and methanol tolerance of Fe-SASCs were even superior to those of Pt/C. Furthermore, Fe-SASCs displayed a maximum power density of 142 mW cm -2 with a current density of 235 mA cm -2 as a cathode catalyst in a zinc-air battery, showing its great potential for practical applications.

Background: Acupoint catgut embedding (ACE) has been proven to be effective and safe in the treatment of obesity, but few studies have been conducted involving its central mechanisms. Our previous study has demonstrated the effectiveness of Shu-Mu ACE in the treatment of abdominal obesity (AO). However, the neurological mechanism of Shu-Mu ACE for weight loss has not yet been elucidated. The mechanism of the combination of the Shu and Mu acupoints may be related to the central integrative effects of the brain. This paper aims to explore the potential neural mechanisms of Shu-Mu ACE in female patients with AO., Methods and Analysis: A total of 100 eligible female AO patients and 20 healthy female subjects will be recruited for this study. 100 AO patients will be randomly allocated to five groups: Shu-Mu ACE (Group A), Shu ACE (Group B), Mu ACE (Group C), sham ACE (Group D), and waiting-list (Group E). Treatment will be administrated once every two weeks for 12 weeks. The body mass index (BMI), waist circumference (WC), Visual Analog Scales (VAS) of appetite, Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS) will be utilized to evaluate the clinical efficacy. Outcomes will be assessed at baseline and at each time point of treatment. Multimodal MRI will be performed at baseline and after 12-week treatment and the results will be used to investigate the neural mechanisms of ACE for obesity. Neurological changes and clinical data will be analysed for correlation., Discussions: This study hypothesized that Shu-Mu ACE therapy has a synergistic effect and may treat AO by modulating the neuropathological alterations in the brain. Our findings will demonstrate the neurological mechanism of AO treated by "Shu-Mu" Acupoint Catgut Embedding and compatibility relation., Trial Registration: This trial is registered at the Chinese Clinical Trial Registration Center (No. ChiCTR2100048920)., 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., (© 2023 Li et al.)

Background: Abdominal obesity (AO) is not only a health issue, but also a serious impact on women's work and life. The article of acupoint catgut embedding (ACE) on AO has already been accepted to be published and showed significant effect. However, whether ACE is effective for abdominally obese female with strong appetite is still unclear., Methods: This is a mixed analysis of a multicenter, double-blind, randomized controlled trial.Which was conducted in China between July 2018 and March 2020 (n = 101), while with the supplementary samples (n = 22) between April 2020 and June 2022. According to the appetite and intervention methods, 123 abdominally obese female were divided into ACE group with strong appetite (n = 27) and moderate appetite (n = 31), control (non-acupoint catgut embedding) group with strong appetite (n = 37) and moderate appetite (n = 28). Four subgroups were given a 12-week actual intervention period and a 4-week follow-up. Waist circumference (WC), appetite, body weight and BMI were applied and assessed at baseline and after 6, 12 and 16 weeks., Results: In this study, the mean onset age of abdominal obesity in females was 25.27 (8.19) years old. The longer duration of AO, the lower the appetite in females ( p <0.05). At 12 and 16 weeks, ACE group with strong appetite showed significant decrease in WC and appetite than control group with strong appetite ( p <0.01). However, ACE group with moderate appetite showed no significant decrease than control group with moderate appetite in WC, appetite, body weight and BMI ( p >0.05). At 12 and 16 weeks, there was no significant difference in appetite between the ACE groups (strong and moderate appetite)( p >0.05), while there was still a difference between the control groups ( p <0.05)., Conclusion: Younger abdominally obese female had a stronger appetite. ACE own the remarkable therapeutic effects for younger abdominally obese female and showed the perfect effect on appetite-reduction., Competing Interests: The authors declare no conflicts of interest in this work., (© 2022 Zhang et al.)

Introduction: Migraine is a common neurological disorder with a higher prevalence occurring in women. Migraine without aura (MwoA) is the most common type of migraine. In recent years, the safety and effectiveness of acupuncture for migraines have been internationally recognised. Contralateral acupuncture (CAT) (Jùcì) is an ancient classic acupuncture technique from Huang Di Nei Jing that refers to the acupoints on the right side (healthy side) selected for diseases on the left (affected side) and vice versa. Some studies have shown that efficacy of CAT on the painful disorder is even better than ipsilateral acupuncture (IAT), but there remains a lack of high-quality evidence to support it., Methods and Analysis: This is a single-centre, randomised and sham-controlled clinical trial in China with three parallel groups that aim to evaluate the efficacy of CAT in women with unilateral MwoA. 243 participants will be randomly divided into the experimental group (CAT group), control group 1 (IAT group) and control group 2 (sham acupuncture group) (1:1:1 allocation ratio). Each group will be given 30-minute treatment sessions, once every other day, approximately three times per week, for a total of 24 treatments and follow-up visits two times. The primary outcome is the changes in days of migraine attacks. The secondary outcomes are frequency of migraine attacks, intensity of migraine, migraine duration, the dose of intake of acute medication, the Migraine-Specific Quality of Life Questionnaire, the Migraine Disability Assessment Score, the Headache Impact Test-6 and the Pittsburgh Sleep Quality Index. The data will be collected at the baseline time (week 0), end of treatment (week 4-8) and the follow-up time (week 12-16). Adverse events will be collected and recorded during each treatment., Ethics and Dissemination: Ethics approval was obtained from the Ethics Committee of the Sports Trauma Specialist Hospital of Yunnan Province (2021-01). All participants will provide written informed consent before randomisation. The results of this study will be published in a peer-reviewed journal and presented at conferences., Trial Registration Number: Chinese Clinical Trial Registration Center (ChiCTR2100051479)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The increasing global demand for sustainable energy sources and emerging environmental issues have pushed the development of energy conversion and storage technologies to the forefront of chemical research. Electrochemical carbon dioxide (CO 2 ) conversion provides an attractive approach to synthesizing fuels and chemical feedstocks using renewable energy. On the path to deploying this technology, basic and applied scientific hurdles remain. Copper, as the only metal catalyst that is capable to produce C 2+ fuels from CO 2 reduction (CO 2 R), still faces challenges in the improvement of electrosynthesis pathways for highly selective fuel production. In this regard, mechanistically understanding CO 2 R on Cu-based electrocatalysts, particularly identifying the structure-function correlation, is crucial. Here, a broad view of the variable structural parameters and their complex interplay in CO 2 R catalysis on Cu was given, with the purpose of providing deep insights and guiding the future rational design of CO 2 R electrocatalysts. First, this Review described the progress and recent advances in the development of well-defined nanostructured catalysts and the mechanistic understanding on the influences from a particular structure of a catalyst, such as facet, defects, morphology, oxidation state, composition, and interface. Next, the in-situ dynamic restructuring of Cu was presented. The importance of operando characterization methods to understand the catalyst structure-sensitivity was also discussed. Finally, some perspectives on the future outlook for electrochemical CO 2 R were offered., (© 2022 Wiley-VCH GmbH.)

Tomato yellow leaf curl virus (TYLCV) is known to encode 6 canonical viral proteins. Our recent study revealed that TYLCV also encodes some additional small proteins with potential virulence functions. The fifth ORF of TYLCV in the complementary sense, which we name C5, is evolutionarily conserved, but little is known about its expression and function during viral infection. Here, we confirmed the expression of the TYLCV C5 by analyzing the promoter activity of its upstream sequences and by detecting the C5 protein in infected cells by using a specific custom-made antibody. Ectopic expression of C5 using a potato virus X (PVX) vector resulted in severe mosaic symptoms and higher virus accumulation levels followed by a burst of reactive oxygen species (ROS) in Nicotiana benthamiana plants. C5 was able to effectively suppress local and systemic post-transcriptional gene silencing (PTGS) induced by single-stranded GFP but not double-stranded GFP, and reversed the transcriptional gene silencing (TGS) of GFP. Furthermore, the mutation of C5 in TYLCV inhibited viral replication and the development of disease symptoms in infected plants. Transgenic overexpression of C5 could complement the virulence of a TYLCV infectious clone encoding a dysfunctional C5. Collectively, this study reveals that TYLCV C5 is a pathogenicity determinant and RNA silencing suppressor, hence expanding our knowledge of the functional repertoire of the TYLCV proteome., (© 2022. The Author(s).)

ABSTRACT Enterovirus A71 (EV-A71) can cause hand, foot and mouth disease with neurological and systemic complications, most frequently affecting children and infants. We describe a cis- acting replication element ( cre ) with a conserved stem-loop structure within the EV-A71 2C-coding region. By site-directed mutagenesis and reverse genetics using the EV-A71 full-length genome and the EV-A71 replicon containing the firefly luciferase reporter gene in place of the P1 region, the stem-loop structure and the AAACA in the loop of the cre were confirmed to be required for the EV-A71 replication phenotype. EV-A71 genomes containing a mutation at the first or third A residue of AAACA could not be recovered. Insertion of a wild-type cre from EV-A71 or poliovirus in the 5'UTR led to successful recovery of the replication of nonviable mutants. Furthermore, the cre mutants showed lower binding capacity with the host cellular factor IGF2BP2, knockdown of which resulted in a significant decrease in EV-A71 production. All the available evidence shows the location independence but functional importance of the interaction of the cre with the cellular host for efficient production of EV-A71, contributing to the growing body of knowledge regarding picornavirus cre s.

Geminiviruses are plant viruses with limited coding capacity. Geminivirus-encoded proteins are traditionally identified by applying a 10-kDa arbitrary threshold; however, it is increasingly clear that small proteins play relevant roles in biological systems, which calls for the reconsideration of this criterion. Here, we show that geminiviral genomes contain additional ORFs. Using tomato yellow leaf curl virus, we demonstrate that some of these small ORFs are expressed during the infection, and that the encoded proteins display specific subcellular localizations. We prove that the largest of these additional ORFs, which we name V3, is required for full viral infection, and that the V3 protein localizes in the Golgi apparatus and functions as an RNA silencing suppressor. These results imply that the repertoire of geminiviral proteins can be expanded, and that getting a comprehensive overview of the molecular plant-geminivirus interactions will require the detailed study of small ORFs so far neglected., (© 2021. The Author(s).)

The electrochemical conversion of CO 2 to valuable fuels is a plausible solution to meet the soaring need for renewable energy sources. However, the practical application of this process is limited by its poor selectivity due to scaling relations. Here we introduce the rational design of the monolayer hexagonal boron nitride/copper (h-BN/Cu) interface to circumvent scaling relations and improve the electrosynthesis of CH 4 . This catalyst possesses a selectivity of >60% toward CH 4 with a production rate of 15 μmol·cm -2 ·h -1 at -1.00 V vs RHE, along with a much smaller decaying production rate than that of pristine Cu. Both experimental and theoretical calculations disclosed that h-BN/Cu interfacial perimeters provide specific chelating sites to immobilize the intermediates, which accelerates the conversion of *CO to *CHO. Our work reports a novel Cu catalyst engineering strategy and demonstrates the prospect of monolayer h-BN contributing to the design of heterostructured CO 2 reduction electrocatalysts for sustainable energy conversion.

Neurological manifestations are frequently reported in the COVID-19 patients. Neuromechanism of SARS-CoV-2 remains to be elucidated. In this study, we explored the mechanisms of SARS-CoV-2 neurotropism via our established non-human primate model of COVID-19. In rhesus monkey, SARS-CoV-2 invades the CNS primarily via the olfactory bulb. Thereafter, viruses rapidly spread to functional areas of the central nervous system, such as hippocampus, thalamus, and medulla oblongata. The infection of SARS-CoV-2 induces the inflammation possibly by targeting neurons, microglia, and astrocytes in the CNS. Consistently, SARS-CoV-2 infects neuro-derived SK-N-SH, glial-derived U251, and brain microvascular endothelial cells in vitro. To our knowledge, this is the first experimental evidence of SARS-CoV-2 neuroinvasion in the NHP model, which provides important insights into the CNS-related pathogenesis of SARS-CoV-2.

Background & Aims: Gastrointestinal (GI) manifestations have been increasingly reported in patients with coronavirus disease 2019 (COVID-19). However, the roles of the GI tract in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are not fully understood. We investigated how the GI tract is involved in SARS-CoV-2 infection to elucidate the pathogenesis of COVID-19., Methods: Our previously established nonhuman primate (NHP) model of COVID-19 was modified in this study to test our hypothesis. Rhesus monkeys were infected with an intragastric or intranasal challenge with SARS-CoV-2. Clinical signs were recorded after infection. Viral genomic RNA was quantified by quantitative reverse transcription polymerase chain reaction. Host responses to SARS-CoV-2 infection were evaluated by examining inflammatory cytokines, macrophages, histopathology, and mucin barrier integrity., Results: Intranasal inoculation with SARS-CoV-2 led to infections and pathologic changes not only in respiratory tissues but also in digestive tissues. Expectedly, intragastric inoculation with SARS-CoV-2 resulted in the productive infection of digestive tissues and inflammation in both the lung and digestive tissues. Inflammatory cytokines were induced by both types of inoculation with SARS-CoV-2, consistent with the increased expression of CD68. Immunohistochemistry and Alcian blue/periodic acid-Schiff staining showed decreased Ki67, increased cleaved caspase 3, and decreased numbers of mucin-containing goblet cells, suggesting that the inflammation induced by these 2 types of inoculation with SARS-CoV-2 impaired the GI barrier and caused severe infections., Conclusions: Both intranasal and intragastric inoculation with SARS-CoV-2 caused pneumonia and GI dysfunction in our rhesus monkey model. Inflammatory cytokines are possible connections for the pathogenesis of SARS-CoV-2 between the respiratory and digestive systems., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Recently, the emerging conceptual valley-related devices have attracted much attention due to the progress on generating, controlling, and detecting the valley degree of freedom in the transition metal dichalcogenide (TMD) monolayers. In general, it is known that achieving valley degree of freedom with long valley lifetime is crucial in the implementation of valleytronic devices. Here, we provide a brief introduction of the basic understandings of valley degree of freedom. We as well review the recent experimental advancement in the modulation of valley degree of freedom. The strategies include optical/magnetic/electric field tuning, moiré patterns, plasmonic metasurface, defects and strain engineering. In addition, we summarize the corresponding mechanisms, which can help to obtain large degree of polarization and long valley lifetimes in monolayer TMDs. Based on these methods, two-dimensional valley-optoelectronic systems based on TMD heterostructures can be constructed, providing opportunities for such as the new paradigm in data processing and transmission. Challenges and perspectives on the development of valleytronics are highlighted as well.

Objectives: Bispectral index (BIS) can reflect the depth of propofol sedation. This study aims to compare the anesthetic satisfaction, anesthetic dose, and hemodynamic changes between closed-loop target controlled infusion (CLTCI) and open-loop target controlled infusion (OLTCI) during abdominal surgery., Methods: From December 2016 to December 2018, 70 patients undergoing abdominal surgery under general anesthesia were selected in Beijing Hospital, including 51 males and 19 females, at the age from 49 to 65 years old. They were classified as grade I-II by the American Society of anesthesiologists (ASA) and were randomly divided into the CLTCI group and the OLTCI group ( n =35). The CLTCI group received propofol CLTCI, and the target BIS value was set between 45 to 55; in the OLTCI group, the plasma target concentration was adjusted to maintain the BIS value between 40 to 60. Both groups were given remifentanil by target controlled infusion, and the plasma target concentration was 6.0 ng/mL. The percentages of adequate anesthesia time, deep anesthesia time, and light anesthesia time were calculated. The total induction dose of propofol, continuous infusion dose of propofol, predicted target propofol concentration of effect chamber, and continuous infusion dose of remifentanil were calculated. The times of automatic adjustment of propofol concentration in closed-loop system and manual adjustment of propofol concentration in the OLTCI group were recorded. Hemodynamic indexes were recorded, and the percentage of target mean arterial pressure (MAP) maintenance time and target heart rate (HR) maintenance time were calculated. Anesthesia time, operation time, recovery time, and extubation time were compared between the 2 groups., Results: In the induction stage, the percentage of adequate anesthesia time in the CLTCI group was higher than that in the OLTCI group, and the percentage of deep anesthesia time in the CLTCI group was significantly lower than that in the OLTCI group (both P <0.05). In the maintenance stage, the percentage of light anesthesia time in the CLTCI group was significantly lower than that in the OLTCI group ( P <0.05). The times of propofol adjustment in the CLTCI group was significantly more than that in the OLTCI group ( P <0.001). The total induction dose of propofol in the CLTCI group was less than that in the OLTCI group ( P <0.05), but there were no significant differences in the continuous infusion dose of propofol, predicted target concentration of propofol, continuous infusion dose of remifentanil between the 2 groups (all P >0.05). There were no significant differences in the percentages of target MAP maintenance time and target HR maintenance time between the 2 groups (both P >0.05). There was no intraoperative awareness in both groups, and there were no significant differences in operation time and anesthesia time between the 2 groups (both P >0.05)., Conclusions: Compared with propofol OLTCI, anesthesia with propofol CLTCI under BIS guidance can maintain a more appropriate depth of anesthesia sedation and more stable hemodynamics.

Identification of a suitable nonhuman primate (NHP) model of COVID-19 remains challenging. Here, we characterized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in three NHP species: Old World monkeys Macaca mulatta (M. mulatta) and Macaca fascicularis (M. fascicularis) and New World monkey Callithrix jacchus (C. jacchus). Infected M. mulatta and M. fascicularis showed abnormal chest radiographs, an increased body temperature and a decreased body weight. Viral genomes were detected in swab and blood samples from all animals. Viral load was detected in the pulmonary tissues of M. mulatta and M. fascicularis but not C. jacchus. Furthermore, among the three animal species, M. mulatta showed the strongest response to SARS-CoV-2, including increased inflammatory cytokine expression and pathological changes in the pulmonary tissues. Collectively, these data revealed the different susceptibilities of Old World and New World monkeys to SARS-CoV-2 and identified M. mulatta as the most suitable for modeling COVID-19.

Since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became a pandemic event in the world, it has not only caused huge economic losses, but also a serious threat to global public health. Many scientific questions about SARS-CoV-2 and Coronavirus disease (COVID-19) were raised and urgently need to be answered, including the susceptibility of animals to SARS-CoV-2 infection. Here we tested whether tree shrew, an emerging experimental animal domesticated from wild animal, is susceptible to SARS-CoV-2 infection. No clinical signs were observed in SARS-CoV-2 inoculated tree shrews during this experiment except the increasing body temperature particularly in female animals. Low levels of virus shedding and replication in tissues occurred in all three age groups. Notably, young tree shrews (6 months to 12 months) showed virus shedding at the earlier stage of infection than adult (2 years to 4 years) and old (5 years to 7 years) animals that had longer duration of virus shedding comparatively. Histopathological examine revealed that pulmonary abnormalities were the main changes but mild although slight lesions were also observed in other tissues. In summary, tree shrew is less susceptible to SARS-CoV-2 infection compared with the reported animal models and may not be a suitable animal for COVID-19 related researches. However, tree shrew may be a potential intermediate host of SARS-CoV-2 as an asymptomatic carrier.

Over the past decade, two-dimensional (2D) transition metal dichalcogenides (TMDCs) have attracted tremendous research interest for future electronics owing to their atomically thin thickness, compelling properties and various potential applications. However, interface engineering including contact optimization and channel modulations for 2D TMDCs represents fundamental challenges in ultimate performance of ultrathin electronics. This article provides a comprehensive overview of the basic understanding of contacts and channel engineering of 2D TMDCs and emerging electronics benefiting from these varying approaches. In particular, we elucidate multifarious contact engineering approaches such as edge contact, phase engineering and metal transfer to suppress the Fermi level pinning effect at the metal/TMDC interface, various channel treatment avenues such as van der Waals heterostructures, surface charge transfer doping to modulate the device properties, and as well the novel electronics constructed by interface engineering such as diodes, circuits and memories. Finally, we conclude this review by addressing the current challenges facing 2D TMDCs towards next-generation electronics and offering our insights into future directions of this field.

Low-symmetry layered materials such as black phosphorus (BP) have been revived recently due to their high intrinsic mobility and in-plane anisotropic properties, which can be used in anisotropic electronic and optoelectronic devices. Since the anisotropic properties have a close relationship with their anisotropic structural characters, especially for materials with low-symmetry, exploring new low-symmetry layered materials and investigating their anisotropic properties have inspired numerous research efforts. In this paper, we review the recent experimental progresses on low-symmetry layered materials and their corresponding anisotropic electrical transport, magneto-transport, optoelectronic, thermoelectric, ferroelectric, and piezoelectric properties. The boom of new low-symmetry layered materials with high anisotropy could open up considerable possibilities for next-generation anisotropic multifunctional electronic devices., Competing Interests: The authors declare no competing financial interests., (This journal is © The Royal Society of Chemistry.)

By virtue of the layer-dependent band structure and valley-selected optical/electronic properties, atomically layered transition-metal dichalcogenides (TMDs) exhibit great potentials such as in valleytronics and quantum devices, and have captured significant attentions. Precise control of the optical and electrical properties of TMDs is always the pursuing goal for real applications, and constructing advanced structures that allow playing with more degrees of freedom may hold the key. Here, we introduce a triangular inkslab-like WSe 2 homojunction with a monolayer in the inner surrounded by a multilayer frame. Benefit from this interesting structure, the photoluminescence (PL) peaks redshift up to 50 meV and the charge density increases about 6 times from the center to the edge region of the inner monolayer. We demonstrated that the Se-deficient multilayer frame offers the excessive free electrons for the generation of the electron density gradient inside the monolayer, which also results in the spatial variation and distribution gradient of a series of exciton complexes. Furthermore, we observed the strong rectifying characteristic and clear photovoltaic response across the homojunction through measuring and mapping the photocurrent of the devices. Our result provides another route for efficient modulation of the exciton-complex emissions of TMDs, which is exceptionally desirable for the "layer- and charge-engineered" photonic and optoelectronic devices.

We carefully prepared interfacial Al-doped (IAD) and interfacial natively-doped (IND) ZnO nanowires (NWs) by introducing atomic-layer interfacial Δ-doping between the two steps of CVD growth. Variable-temperature electron transport as well as magnetotransport behaviours of these NWs were systematically investigated. By virtue of the unique architecture and the quality-guaranteed growth technique, a series of quantum interference effects were clearly observed in the IAD ZnO NWs, including weak localization, universal conductance fluctuation and Altshuler-Aronov-Spivak oscillations. The phase-coherence length (L φ ) of electrons exceeds 100 nm in the IAD ZnO NWs, much longer than those in the IND ones and most conventionally doped ZnO NWs. This ability to efficiently manipulate a variety of quantum interference effects in ZnO NWs is very desirable for applications in nano-optoelectronics, nano- & quantum-electronics and solid-state quantum computing.

Low plasma level of high density lipoprotein cholesterol (HDL-c) was an independent risk factor for cardio vascular disorder, and associated with poor outcomes in pulmonary arterial hypertension. To compare the effects of vegetarian diets and omnivorous diets on HDL-c in plasma, we identified cross-sectional and cohort studies related to HDL-c listed on PubMed and ISI Web of Knowledge as well as the corresponding references (until Nov, 2013). Twelve studies with a total of 4177 individuals were selected for meta-analysis. This meta-analysis indicates that vegetarian diets did not alter plasma HDL-c concentrations, as it wasn't initially expected by the authors [Standardized Mean Difference (SMD) = 0.02 mmol/l; 95% confidence interval (CI): -0.19 to 0.22 mmol/l]. In Asia and Latin America countries, no significant differences in HDL-c levels between vegetarians and omnivores were found (SMD = -0.09 mmol/l; 95% CI: -0.43 to 0.25 mmol/l). In Europe and North America countries, the plasma level of HDL-c was also not different between the two diets (SMD = 0.09 mmol/l; 95% CI: -0.19 to 0.36 mmol/l). In light of this meta-analysis, we conclude that there is no evidence that plasma HDL-c levels differs in vegetarians and omnivores, even after adjusting for cultural circumstances.