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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a serious impact on the world. In this study, small RNAs from the blood of COVID-19 patients with moderate or severe symptoms were extracted for high-throughput sequencing and analysis. Interestingly, the levels of a special group of tRNA-derived small RNAs (tsRNAs) were found to be dramatically upregulated after SARS-CoV-2 infection, particularly in coronavirus disease 2019 (COVID-19) patients with severe symptoms. In particular, the 3'CCA tsRNAs from tRNA-Gly were highly consistent with the inflammation indicator C-reactive protein (CRP). In addition, we found that the majority of significantly changed microRNAs (miRNAs) were associated with endoplasmic reticulum (ER)/unfolded protein response (UPR) sensors, which may lead to the induction of proinflammatory cytokine and immune responses. This study found that SARS-CoV-2 infection caused significant changes in the levels of stress-associated small RNAs in patient blood and their potential functions. Our research revealed that the cells of COVID-19 patients undergo tremendous stress and respond, which can be reflected or regulated by small non-coding RNA (sncRNAs), thus providing potential thought for therapeutic intervention in COVID-19 by modulating small RNA levels or activities., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)

The micronucleomics test can comprehensively display a variety of harmful endpoints, such as DNA damage and repair, chromosome breakage or loss and cell growth inhibition, with fast, simple and economical feature. Micronucleomics is not only widely used in the comprehensive assessment of the types and modes of genetic action of exogenous chemicals (such as drugs, food additives, cosmetics, environmental pollutants, etc.), but also plays an important role in the screening and risk assessment of cancer population at high risk. However, the traditional micronucleomics image counting method has the characteristics of time-consuming, low accuracy, and high cost, which cannot meet the current analysis requirements of large-scale, multi-index, rapidity, high precision and visualization. In recent years, with the rapid development of the era of precision medicine based on big data, visualized analysis of new micronucleomics based on machine learning and detection strategies based on deep learning have shown a good application prospect. This review, based on the application value of micronucleomics, systematically compares the traditional and new artificial intelligence counting of micronucleus images, and discusses the future direction of micronucleus image detection.

Background: Pancreatitis is the most common complication of pancreatic extracorporeal shock wave lithotripsy (ESWL). There has been little research into effective prevention of post-ESWL pancreatitis. Therefore, we aimed to assess the efficacy of prophylactic rectal indometacin in preventing post-ESWL pancreatitis., Methods: In this double-blind, randomised, placebo-controlled trial done at Changhai Hospital (Shanghai, China), patients aged 18 years or older with chronic pancreatitis and pancreatic stones (>5 mm in diameter) who were eligible for treatment with ESWL were randomly allocated using a computer-generated randomisation table, in a 1:1 ratio, to receive 100 mg rectal indometacin or identical glycerin (placebo) suppositories 30 min before ESWL. Patients, endoscopists, and outcome assessors were masked to group allocation. The primary outcome was the incidence of post-ESWL pancreatitis within 24 h of ESWL, analysed by the intention-to-treat principle. This study is registered with ClinicalTrials.gov, number NCT02797067., Findings: Between May 31, 2016, and June 26, 2019, 1370 patients were enrolled, with 685 patients randomly assigned to the rectal indometacin group and 685 patients to the placebo group. All patients received their allocated intervention and completed final follow-up, and were included in the intention-to-treat analysis. Post-ESWL pancreatitis occurred in 60 (9%) patients in the rectal indometacin group and 84 (12%) patients in the placebo group (relative risk 0·71, 95% CI 0·52-0·98; p=0·042). Transient adverse events occurred in 235 (34%) patients in the rectal indometacin group and 252 (37%) patients in the placebo group, with asymptomatic hyperamylasaemia being the most common (189 [28%] patients vs 197 [29%] patients). No difference was noted between groups in the incidence of other complications and transient adverse events., Interpretation: Pre-procedural administration of rectal indometacin is an efficacious and safe means of reducing the incidence of post-ESWL pancreatitis., Funding: Programs of Shanghai Municipal Government and the "Ten Thousand Plan"-National High Level Talents Special Support Plan., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Rheumatoid arthritis (RA) often leads to functional disabilities and deformities. MiRNA plays a vital role in cell pyroptosis. Nevertheless, the function and underlying mechanism of miR-144-3p in pyroptosis during the progression of RA remains unclear. In this study, N1511 cells were stimulated with IL-1β to construct a RA model. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay was performed to assess the cell viability. Cell pyroptosis was detected by flow cytometry. The levels of inflammatory cytokines (TNF-α, IL-6, and IL-18) were assessed by enzyme-linked immunosorbent assay (ELISA). The relationship among specific protein 1 (SP1), microRNA-144-3p (miR-144-3p), and phosphatase and tensin homolog (PTEN) was explored by dual-luciferase reporter assay, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (ChIP), respectively. The level of miR-144-3p in N1511 cells was upregulated by IL-1β. MiR-144-3p knockdown inhibited IL-1β-induced pyroptosis in N1511 cells, and the expressions of NOD-like receptor family pyrin domain containing 3 (NLRP3), Cleaved caspase-1, Gasdermin D (GSDMD), and Cleaved caspase-3 in IL-1β-stimulated N1511 cells were increased. The levels of inflammatory cytokines in N1511 cells were increased by IL-1β, which were restored by miR-144-3p knockdown. MiR-144-3p knockdown abolished IL-1β-induced inactivation of putative kinase 1 (PINK1)/Parkin RBR E3 ubiquitin-protein (Parkin) signalling. Moreover, transcription factor SP1 could upregulate miR-144-3p expression and miR-144-3p negatively regulated PTEN expression. In summary, MiR-144-3p induced by SP1 could promote IL-1β-induced chondrocyte pyroptosis via inhibiting PTEN expression and suppressing the activation of PINK1/Parkin signalling, which provided a new strategy against RA.

Objective: To evaluate the feasibility and accuracy of mixed reality combined with surgical navigation in oral and maxillofacial tumor surgery., Methods: Retrospective analysis of data of seven patients with oral and maxillofacial tumors who underwent surgery between January 2019 and January 2021 using a combination of mixed reality and surgical navigation. Virtual surgical planning and navigation plan were based on preoperative CT datasets. Through IGT-Link port, mixed reality workstation was synchronized with surgical navigation, and surgical planning data were transferred to the mixed reality workstation. Osteotomy lines were marked with the aid of both surgical navigation and mixed reality images visualized through HoloLens. Frozen section examination was used to ensure negative surgical margins. Postoperative CT datasets were obtained 1 week after the surgery, and chromatographic analysis of virtual osteotomies and actual osteotomies was carried out. Patients received standard oncological postoperative follow-up., Results: Of the seven patients, four had maxillary tumors and three had mandibular tumors. There were total of 13 osteotomy planes. Mean deviation between the planned osteotomy plane and the actual osteotomy plane was 1.68 ± 0.92 mm; the maximum deviation was 3.46 mm. Chromatographic analysis showed error of ≤3 mm for 80.16% of the points. Mean deviations of maxillary and mandibular osteotomy lines were approximate (1.60 ± 0.93 mm vs. 1.86 ± 0.93 mm). While five patients had benign tumors, two had malignant tumors. Mean deviations of osteotomy lines was comparable between patients with benign and malignant tumors (1.48 ± 0.74 mm vs. 2.18 ± 0.77 mm). Intraoperative frozen pathology confirmed negative resection margins in all cases. No tumor recurrence or complications occurred during mean follow-up of 15.7 months (range, 6-26 months)., Conclusion: The combination of mixed reality technology and surgical navigation appears to be feasible, safe, and effective for tumor resection in the oral and maxillofacial region., 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 Tang, Hu, Soh, Yu, Zhang and Peng.)

tRNA-derived small RNA (tsRNA), a novel type of regulatory small noncoding RNA, plays an important role in physiological and pathological processes. However, the understanding of the functional mechanism of tsRNAs in cells and their role in the occurrence and development of diseases is limited. Here, we integrated multiomics data such as transcriptome, epitranscriptome, and targetome data, and developed novel computer tools to establish tsRFun, a comprehensive platform to facilitate tsRNA research (http://rna.sysu.edu.cn/tsRFun/ or http://biomed.nscc-gz.cn/DB/tsRFun/). tsRFun evaluated tsRNA expression profiles and the prognostic value of tsRNAs across 32 types of cancers, identified tsRNA target molecules utilizing high-throughput CLASH/CLEAR or CLIP sequencing data, and constructed the interaction networks among tsRNAs, microRNAs, and mRNAs. In addition to its data presentation capabilities, tsRFun offers multiple real-time online tools for tsRNA identification, target prediction, and functional enrichment analysis. In summary, tsRFun provides a valuable data resource and multiple analysis tools for tsRNA investigation., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

To overcome the low accuracy, poor reliability, and delay in the current drought prediction models, we propose a new extreme learning machine (ELM) based on an improved variational mode decomposition (VMD). The model first redefines the output of the hidden layer of the ELM model with orthogonal triangular matrix decomposition (QR) to construct an orthogonal triangular ELM (QR-ELM), and then introduces an online sequence learning mechanism (OS) into the QR-ELM to construct an online sequence OR-ELM (OS-QR-ELM), which effectively improves the efficiency of the ELM model. The mutual information extension method was then used to extend both ends of the original signal to improve the VMD end effect. Finally, VMD and OS-QR-ELM were combined to construct a drought prediction method based on the VMD-OS-QR-ELM. The reliability and accuracy of the VMD-OS-QR-ELM model were improved by 86.19% and 93.20%, respectively, compared with those of the support vector regression model combined with empirical mode decomposition. Furthermore, the calculation efficiency of the OS-QR-ELM model was increased by 88.65% and 85.32% compared with that of the ELM and QR-ELM models, respectively., Competing Interests: The authors have declared that no competing interests exist.

Androgen receptor (AR), a ligand-activated transcription factor, is a master regulator in the development and progress of prostate cancer (PCa). A major challenge for the clinically used AR antagonists is the rapid emergence of resistance induced by the mutations at AR ligand binding domain (LBD), and therefore the discovery of novel anti-AR therapeutics that can combat mutation-induced resistance is quite demanding. Therein, blocking the interaction between AR and DNA represents an innovative strategy. However, the hits confirmed targeting on it so far are all structurally based on a sole chemical scaffold. In this study, an integrated docking-based virtual screening (VS) strategy based on the crystal structure of the DNA binding domain (DBD) of AR was conducted to search for novel AR antagonists with new scaffolds and 2-(2-butyl-1,3-dioxoisoindoline-5-carboxamido)-4,5-dimethoxybenzoicacid (Cpd39) was identified as a potential hit, which was competent to block the binding of AR DBD to DNA and showed decent potency against AR transcriptional activity. Furthermore, Cpd39 was safe and capable of effectively inhibiting the proliferation of PCa cell lines (i.e., LNCaP, PC3, DU145, and 22RV1) and reducing the expression of the genes regulated by not only the full-length AR but also the splice variant AR-V7. The novel AR DBD-ARE blocker Cpd39 could serve as a starting point for the development of new therapeutics for castration-resistant PCa., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)

Introduction: Acute pancreatitis (AP) is a common clinical pancreatic disease. Patients with different severity levels have different clinical outcomes. With the advantages of algorithms, machine learning (ML) has gradually emerged in the field of disease prediction, assisting doctors in decision-making., Methods: A systematic review was conducted using the PubMed, Web of Science, Scopus, and Embase databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Publication time was limited from inception to 29 May 2021. Studies that have used ML to establish predictive tools for AP were eligible for inclusion. Quality assessment of the included studies was conducted in accordance with the IJMEDI checklist., Results: In this systematic review, 24 of 2,913 articles, with a total of 8,327 patients and 47 models, were included. The studies could be divided into five categories: 10 studies (42%) reported severity prediction; 10 studies (42%), complication prediction; 3 studies (13%), mortality prediction; 2 studies (8%), recurrence prediction; and 2 studies (8%), surgery timing prediction. ML showed great accuracy in several prediction tasks. However, most of the included studies were retrospective in nature, conducted at a single centre, based on database data, and lacked external validation. According to the IJMEDI checklist and our scoring criteria, two studies were considered to be of high quality. Most studies had an obvious bias in the quality of data preparation, validation, and deployment dimensions., Conclusion: In the prediction tasks for AP, ML has shown great potential in assisting decision-making. However, the existing studies still have some deficiencies in the process of model construction. Future studies need to optimize the deficiencies and further evaluate the comparability of the ML systems and model performance, so as to consequently develop high-quality ML-based models that can be used in clinical practice., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: To observe the curative effect of one-stage reconstruction of anterior cruciate ligament(ACL), posterior cruciate ligament (PCL) and medial collateral ligament (MCL) in patients with KD-Ⅲ-M knee injury, and to compare the operation time, hospitalization cost and curative effect after arthroscopic reconstruction of PCL with LARS artificial ligament and autogenous hamstring tendon, ACL reconstruction with autogenous hamstring tendon and MCL repair combined with limited incision., Methods: From March 2016 to January 2019, a total of 36 patients met the criteria of this study. Twenty patients in group A were treated with autogenous hamstring tendon reconstruction of ACL and PCL and repair of MCL, including 17 males and 3 females, with an average age of (34.7±9.2) years old. Sixteen patients in group B with LARS artificial ligament reconstruction of PCL, with an autogenous hamstring tendon reconstruction of PCL and MCL repair as before as group B, including 15 males and 1 female, with an average age of (36.8±8.6) years old. The operation time, hospitalization time and total hospitalization cost were compared between the two groups. The preoperative and postoperative functions of the two groups were evaluated by Hospital for Sepcial Surgery (HSS) score and Lysholm score respectively, and the curative effects were compared within and between groups., Results: All the patients in the two groups were followed up for at least 1 year. There were no complications such as infection and poor wound healing in both groups. There was significant difference in operation time between (120.25±9.55) min in group A and (106.63±8.85) min in group B ( P <0.01). The average hospitalization days in group A was (10.60±1.64) days, while that in group B was (10.38±1.59) days. There was no significant difference between the two groups ( P >0.05). The HSS score of group A increased from preoperative 32.95±5.03 to postoperative 84.70±5.72 ( P <0.01), and that of group B increased from preoperative 33.81±4.10 to postoperative 85.00±5.25 ( P <0.01). The Lyshlom score in group A increased from preoperative 21.10±3.46 to postoperative 80.25±5.75 ( P <0.01), and in group B increased from preoperative 21.56±3.01 to postoperative 80.00±4.30( P <0.01). There was no significant difference in preoperative and postoperative scores between the two groups( P >0.05)., Conclusion: There was no significant difference in the average hospitalization days between the two groups, but the operation time in group A was longerthan that in group B, and the hospitalization cost in group B was higher than that in group A. There was no difference in HSS score and Lysholm score before and follow-up for a certain period of time after operation.

Liver development is a highly complex process that is regulated by the orchestrated interplay of epigenetic regulators, transcription factors, and microRNAs (miRNAs). Owing to the lack of global in vivo targets of all miRNAs during liver development, the mechanisms underlying the dynamic control of hepatocyte differentiation by miRNAs remain elusive. Here, using Argonaute (Ago) high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP) in the mouse liver at different developmental stages, we characterized massive Ago-binding RNAs and obtained a genome-wide map of liver miRNA-mRNA interactions. The dynamic changes of five clusters of miRNAs and their potential targets were identified to be differentially involved at specific stages, a dozen of high abundant miRNAs and their epigenetic regulation by super-enhancer were found during liver development. Remarkably, miR-122, a liver-specific and most abundant miRNA in newborn and adult livers, was found by its targetome and pathway reporter analyses to regulate the Hippo pathway, which is crucial for liver size control and homeostasis. Mechanistically, we further demonstrated that miR-122 negatively regulates the outcomes of the Hippo pathway transcription factor TEAD by directly targeting a number of hippo pathway regulators, including the coactivator TAZ and a key factor of the phosphatase complex PPP1CC, which contributes to the dephosphorylation of YAP, another coactivator downstream of the Hippo pathway. This study identifies for the first time the genome-wide miRNA targetomes during mouse liver development and demonstrates a novel mechanism of terminal differentiation of hepatocytes regulated by the miR-122/Hippo pathway in a coordinated manner. As the Hippo pathway plays important roles in cell proliferation and liver pathological processes like inflammation, fibrosis, and hepatocellular carcinoma (HCC), our study could also provide a new insight into the function of miR-122 in liver pathology., (© 2021. The Author(s).)

High dose (0.3%) of dietary histamine can cause adverse effects on growth performance, innate immunity, and gut health in juvenile grouper ( Epinephelus coioides ). In the present study, three autochthonous probiotics ( Bacillus pumilus SE5, Psychrobacter sp. SE6, and Bacillus clausii DE5) were supplemented separately to diets containing 0.3% of histamine and their effects on growth performance, innate immunity, and gut health of grouper ( E. coioides ) were evaluated in a 56-day feeding trial. The results showed considerable increase in weight gain, specific growth rate, hepatosomatic index, and decreased feed conversion rate in groupers fed with probiotic-supplemented diets. Supplementation of autochthonous probiotics has improved antioxidant capacity and innate immunity of E. coioides by measuring correlative parameters, such as total antioxidant capacity, superoxide dismutase activity, malondialdehyde content, and so on. Additionally, dietary probiotics have significantly reduced the levels of serum interleukin-1β (at days 28 and 56), fatty acid-binding protein 2, and intestinal trefoil factor (at day 28), and promoted intestinal integrity following remarkably increased muscle thickness and mucosal fold height at day 56, especially in grouper fed with B. pumilus SE5 containing diet ( P < 0.05). On day 56, the gut microbial composition of E. coioides was positively shaped by autochthonous probiotics, the relative abundance of potentially pathogenic Photobacterium decreased while beneficial Lactobacillus increased in fish fed with probiotic strains, especially with B. pumilus SE5 and B. clausii DE5. These results suggest that among the three autochthonous probiotic strains tested, B. pumilus SE5 is showing better efficiency in alleviating the adverse effects of (high levels) dietary histamine by decreasing the expression of inflammatory markers and by improving the growth, innate immunity, and gut health of juvenile grouper E. coioides ., Competing Interests: WY was employed by Xiamen Jiakang Feed Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Yang, Hu, Yang, Ai and Sun.)

Globally, non-small cell lung cancer (NSCLC) is the most common malignancy and its prognosis remains poor because of the lack of reliable early diagnostic biomarkers. The competitive endogenous RNA (ceRNA) network plays an important role in the tumorigenesis and prognosis of NSCLC. Tumor immune microenvironment (TIME) is valuable for predicting the response to immunotherapy and determining the prognosis of NSCLC patients. To understand the TIME-related ceRNA network, the RNA profiling datasets from the Genotype-Tissue Expression and The Cancer Genome Atlas databases were analyzed to identify the mRNAs, microRNAs, and lncRNAs associated with the differentially expressed genes. Weighted gene co-expression network analysis revealed that the brown module of mRNAs and the turquoise module of lncRNAs were the most important. Interactions among microRNAs, lncRNAs, and mRNAs were prognosticated using miRcode, miRDB, TargetScan, miRTarBase, and starBase databases. A prognostic model consisting of 13 mRNAs was established using univariate and multivariate Cox regression analyses and validated by the receiver operating characteristic (ROC) curve. The 22 immune infiltrating cell types were analyzed using the CIBERSORT algorithm, and results showed that the high-risk score of this model was related to poor prognosis and an immunosuppressive TIME. A lncRNA-miRNA-mRNA ceRNA network that included 69 differentially expressed lncRNAs (DElncRNAs) was constructed based on the five mRNAs obtained from the prognostic model. ROC survival analysis further showed that the seven DElncRNAs had a substantial prognostic value for the overall survival (OS) in NSCLC patients; the area under the curve was 0.65. In addition, the high-risk group showed drug resistance to several chemotherapeutic and targeted drugs including cisplatin, paclitaxel, docetaxel, gemcitabine, and gefitinib. The differential expression of five mRNAs and seven lncRNAs in the ceRNA network was supported by the results of the HPA database and RT-qPCR analyses. This comprehensive analysis of a ceRNA network identified a set of biomarkers for prognosis and TIME prediction in NSCLC., Competing Interests: The authors have declared that no competing interests exist.

Background and Aims: The high incidence of osteopathy among patients with chronic pancreatitis (CP) has garnered increased attention over recent years. The aims of this study were to assess the prevalence and risk factors for osteopathy in Chinese patients with CP., Methods: This was a cross-sectional study of CP patients from a large center in China; patients were recruited between 31 January 2017 and 31 January 2018. Bone density and laboratory tests, including bone-related biochemical, inflammatory, and hormone parameters, were assessed prospectively. Differences between patients with and without osteopathy were analyzed. Logistic regression analysis was used to investigate associations between variables., Results: In total, 104 CP patients were enrolled in this study (68.3% idiopathic and 31.7% alcoholic). According to the M-ANNHEIM classification, 87.5% of the patients were at an early stage (0-II). Osteopenia was diagnosed in 30.8% of patients and osteoporosis in 5.8%; thus, a total of 36.5% of patients presented with osteopathy. In multivariate analysis, the independent risk factors for osteopathy in CP patients were age (OR = 1.04; 95% CI = 1.00-1.08; P = 0.030), BMI (OR = 0.72; 95% CI = 0.58-0.89; P = 0.003), and PTH (OR = 0.96; 95% CI = 0.93-1.00; P = 0.022)., Conclusions: This study is the first to report the prevalence of osteopathy in Chinese patients with CP. It found that age and low BMI are significant risk factors for osteopathy. Low PTH (but within the normal range) showed a weak association with osteopathy, which warrants further exploration., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Only few studies have analyzed the global distribution of anesthesia research. This study was designed to reveal the current global research status of anesthesiology., Methods: Articles published between 1999 and 2018 in international journals in the field of anesthesiology were retrieved from the PubMed database. The top 20 ranked countries were identified. The gross domestic product (GDP) of each country was also retrieved to reveal the correlation between research outputs and the economy. The total outputs and outputs per 10 million inhabitants in each country were calculated and compared. To analyze the quality of publications among the top 10 ranked countries, the impact factor (IF), article influence score (AIS), and immediacy index (ImI) were calculated and analyzed. In addition, the keywords of publications were retrieved to conduct co-occurrence analysis in order to determine the research focus in anesthesiology., Results: A total of 112,918 articles were published in 30 selected journals from 1999 to 2018. There was a positive correlation between research outputs and GDP of 10 countries (p < 0.001, r = 0.825). The USA ranked 1st with 21,703 articles, followed by the UK (8393 articles) and Germany (6504 articles). Canada had the highest number of publications per 10 million inhabitants in 2018. The UK had the highest average IF (4.70), average AIS (1.16), and average ImI (1.64) among the 10 countries. The research highlights in the field of anesthesiology included "mechanism and management of pain", "cardiac anesthesia", "pediatric anesthesia and airway management", "analgesia" and "anesthetic agents"., Conclusion: Regarding quantity trend, the output of global production in anesthesiology increased continuously as the number of articles from the high-output countries showed an increasing trend; however, there was still a gap between developing and developed countries in research quality. High-quality research should be encouraged in developing countries., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

In two-dimensional insulators with time-reversal (TR) symmetry, a nonzero local Berry curvature of low-energy massive Dirac fermions can give rise to nontrivial spin and charge responses, even though the integral of the Berry curvature over all occupied states is zero. In this Letter, we present a new effect induced by the electronic Berry curvature. By studying electron-phonon interactions in BaMnSb&#95;{2}, a prototype two-dimensional Dirac material possessing two TR-related massive Dirac cones, we find that the nonzero local Berry curvature of electrons can induce a phonon angular momentum. The direction of this phonon angular momentum is locked to the phonon propagation direction, and thus we refer to it as "phonon helicity" in a way that is reminiscent of electron helicity in spin-orbit-coupled electronic systems. We discuss possible experimental probes of such phonon helicity.

Ginsenoside Rg3 is a steroidal saponin isolated from Panax ginseng. Previous studies have shown that Rg3 treatment downregulates the activity of rapamycin complex 1 (mTORC1) activity and inhibits the growth of cancer cells. However, the inhibitory effect of Rg3 on cancer cells is associated with high concentrations of Rg3 that are difficult to achieve in vivo . The human cervix adenocarcinoma HeLa cells were treated with Rg3. The protein levels of AMP-activated protein kinase alpha (AMPKα), protein kinase B(Akt), ribosomal S6 protein(S6), and Erk were determined by immunoblotting analyses. We used a fluorescent probe to detect reactive oxygen species (ROS) production in living cells. The oxygen consumption rate (OCR) was examined by the Seahorse Extracellular Flux Analyzer. The content of adenosine triphosphate (ATP) was measured by ATPlite kit and Mitotracker was applied to detect the mitochondria. We showed that at lower concentrations, Rg3 activates mTORC1 independent of AKT and AMP-activated protein kinase (AMPK). Rg3 promotes mitochondrial biogenesis and function, increases the oxygen consumption of mitochondria and the content of ATP. This effect is in contrast to that of high concentrations of Rg3, which inhibits cell growth. These findings demonstrate a pro-growth activity of Rg3 that acts through mTORC1 and mitochondrial biogenesis and suggest a dose-dependent effect of Rg3 on tumor cell growth., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Zhang, Ai, Pan, Zhang, Jiang, Hu, Sun, Chen and Lin.)

Background: The relationship between chronic pancreatitis (CP) and acute pancreatitis (AP) is complex and not well understood. CP could be preceded by antecedent episodes of AP., Aims: The aim of this study was to explore both genetic and environmental factors associated with AP episodes before the diagnosis of CP., Methods: This was a cross-sectional study including 1022 patients. Detailed demographic, genetic, and clinical data were collected. Based on the presence of AP episode(s) before diagnosis of CP, patients were divided into AP group (further classified into single episode of AP group and recurrent AP group) and non-AP group. Related factors among these groups were assessed using multivariate logistic regression model., Results: Before diagnosis of CP, 737 patients (72.1%) had a history of AP. Smoking(P = 0.005) and heavy alcohol consumption(P = 0.002) were risk factors for AP while age at CP onset(P < 0.001), harboring the SPINK1 mutation(P < 0.001), diabetes(P < 0.001) and steatorrhea(P < 0.001) were protective factors. Further, alcoholic CP(P = 0.019) was the only independent risk factor for recurrent AP attacks while age at onset of CP(P < 0.001), pancreatic stones(P = 0.024). and pseudocysts(P = 0.018) served as protective factors., Conclusions: SPINK1 mutations served as protective factor for AP episodes, suggesting SPINK1 mutation might play a pathogenic role in CP occurrence with occult clinical manifestations., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Endoscopic intervention combined with extracorporeal shock wave lithotripsy (ESWL) is recommended as the first line therapy for large pancreatic stones, yet both can cause adverse events. The aim of the study was to identify the risk factors for post-procedural pancreatitis., Methods: Consecutive patients with chronic pancreatitis and pancreatic stones treated with both ESWL and subsequent endoscopic retrograde cholangiopancreatography (ERCP) from October 2016 to December 2019 were prospectively enrolled. Multivariate logistic analyses were performed to detect risk factors for post-ESWL and post-ERCP pancreatitis (PEP)., Results: A total of 714 patients (507 males, 45.60 ± 12.52 years) were included in this study. A total of 80 patients (11.2%) developed post-ESWL pancreatitis,while 33 patients (4.6%) suffered from PEP. Steatorrhea (P = .018), multiple stones (P = .043), and stones located at the head combined with the body or tail of the pancreas (P = .015) were identified as independent protective factors for post-ESWL pancreatitis. The history of acute exacerbations (P = .013), post-ESWL pancreatitis (P < .001) and stricture dilation during ERCP (P = .002) were identified as risk factors for PEP., Conclusions: More attention should be paid to patients with post-ESWL pancreatitis, as well as a history of acute exacerbations and stricture dilation during ERCP to prevent PEP. (ClincialTrials.gov number, NCT04619511)., (© 2021 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Ulcerative colitis (UC) is a chronic disease characterized by mucosal and submucosal inflammation, which has a low cure rate and is prone to relapse, due to the immune imbalance of the body. Inhibition of inflammation-related pathways can delay the progression of UC. Toll-like receptor 4 (TLR4) pathway is considered to be one of the important signaling pathways involved in colon inflammation. Eriodictyol (EDT) is a natural flavonoid widely distributed in foodborne plants. EDT plays an important role in the regulation of inflammation and related signaling pathways. However, whether EDT plays a role in UC remains unknown. Herein, we established a TNBS induced animal model of enteritis in Wistar rats. Our data confirmed the establishment of TNBS induced animal model of enteritis and the administration Eriodictyol in Wistar rats. EDT treatment alleviated TNBS-induced intestinal tissue injury in rats. We further found that EDT reduced MPO expression and regulated the cytokine parameters in TNBS-induced intestinal tissues of rats. The levels of TNF-α, IL-1β, IL-6, IL-10, IL-2, and IL-12 were also affected by the treatment of EDT. EDT also affected SOD, CAT, GSH-Px, and MDA level in rats with colitis. Moreover, EDT regulated TNBS-induced TLR4/NF-κB pathway activation, therefore inhibiting the progression of UC. Our results suggest that EDT could be a potential therapeutic agent for UC., (© 2021 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia on behalf of Kaohsiung Medical University.)

Objective: The relationship between SPINK1 and pancreatic cancer (PC) remains controversial. The current study aimed to determine the effect of SPINK1 mutations on PC development among patients with chronic pancreatitis (CP)., Methods: This is a prospective observational study including a large cohort of 965 CP patients with 11-year follow-up. Patients' demographic characteristics and clinical CP outcomes were documented in detail. Genetic testing was performed. The effect of SPINK1 mutations on the clinical development of PC was explored using Cox proportional hazards regression. Subgroup analyses conducted included the consideration of gender, onset age of CP (early- and late-onset), etiologies of CP, smoking, and alcoholic drinking status., Results: PC was diagnosed in 2.5% (24/965) of patients, and the cumulative incidence rates were 0.2%, 0.8%, and 1.5% at 3, 5, and 10 years since the onset of CP, respectively. In this cohort, SPINK1 c.194+2T > C was the most common variant with a proportion of 39.1%. And the risk of PC development varied marginally between patients with and without SPINK1 mutations (Cox HR 0.39(0.14-1.04), P = 0.059). In the subgroup analyses, patients carrying SPINK1 mutations had a significantly lower risk of PC (Cox HR 0.18(0.04-0.80), P = 0.025) in the non-smoking group. SPINK1 mutations showed no significant effect in the other subgroups considered., Conclusions: CP patients harboring SPINK1 mutations do not have an elevated risk of PC development compared to mutation-negative CP patients. On the contrary, SPINK1 mutations may be a protective factor in non-smoking patients with CP., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2021 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Although long noncoding RNAs (lncRNAs) have significant tissue specificity, their expression and variability in single cells remain unclear. Here, we developed ColorCells (http://rna.sysu.edu.cn/colorcells/), a resource for comparative analysis of lncRNAs expression, classification and functions in single-cell RNA-Seq data. ColorCells was applied to 167 913 publicly available scRNA-Seq datasets from six species, and identified a batch of cell-specific lncRNAs. These lncRNAs show surprising levels of expression variability between different cell clusters, and has the comparable cell classification ability as known marker genes. Cell-specific lncRNAs have been identified and further validated by in vitro experiments. We found that lncRNAs are typically co-expressed with the mRNAs in the same cell cluster, which can be used to uncover lncRNAs' functions. Our study emphasizes the need to uncover lncRNAs in all cell types and shows the power of lncRNAs as novel marker genes at single cell resolution., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Hypertrophic growth of cardiomyocytes is one of the major compensatory responses in the heart after physiological or pathological stimulation. Protein synthesis enhancement, which is mediated by the translation of messenger RNAs, is one of the main features of cardiomyocyte hypertrophy. Although the transcriptome shift caused by cardiac hypertrophy induced by different stimuli has been extensively investigated, translatome dynamics in this cellular process has been less studied. Here, we generated a nucleotide-resolution translatome as well as transcriptome data from isolated primary cardiomyocytes undergoing hypertrophy. More than 10,000 open reading frames (ORFs) were detected from the deep sequencing of ribosome-protected fragments (Ribo-seq), which orchestrated the shift of the translatome in hypertrophied cardiomyocytes. Our data suggest that rather than increase the translational rate of ribosomes, the increased efficiency of protein synthesis in cardiomyocyte hypertrophy was attributable to an increased quantity of ribosomes. In addition, more than 100 uncharacterized short ORFs (sORFs) were detected in long noncoding RNA genes from Ribo-seq with potential of micropeptide coding. In a random test of 15 candidates, the coding potential of 11 sORFs was experimentally supported. Three micropeptides were identified to regulate cardiomyocyte hypertrophy by modulating the activities of oxidative phosphorylation, the calcium signaling pathway, and the mitogen-activated protein kinase (MAPK) pathway. Our study provides a genome-wide overview of the translational controls behind cardiomyocyte hypertrophy and demonstrates an unrecognized role of micropeptides in cardiomyocyte biology., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Phase analysis of single-photon emission computed tomography myocardial perfusion imaging provides dyssynchrony information which correlates well with assessments by echocardiography, but the independent prognostic significance is not well defined. This study assessed the independent prognostic value of single-photon emission computed tomography-myocardial perfusion imaging phase analysis in the largest multinational registry to date across all modalities., Methods: From the REFINE SPECT (Registry of Fast Myocardial Perfusion Imaging With Next Generation SPECT), a total of 19 210 patients were included (mean age 63.8±12.0 years and 56% males). Poststress total perfusion deficit, left ventricular ejection fraction, and phase variables (phase entropy, bandwidth, and SD) were obtained automatically. Cox proportional hazards analyses were performed to assess associations with major adverse cardiac events (MACE)., Results: During a follow-up of 4.5±1.7 years, 2673 (13.9%) patients experienced MACE. Annualized MACE rates increased with phase variables and were ≈4-fold higher between the second and highest decile group for entropy (1.7% versus 6.7%). Optimal phase variable cutoff values stratified MACE risk in patients with normal and abnormal total perfusion deficit and left ventricular ejection fraction. Only entropy was independently associated with MACE. The addition of phase entropy significantly improved the discriminatory power for MACE prediction when added to the model with total perfusion deficit and left ventricular ejection fraction ( P <0.0001)., Conclusions: In a largest to date imaging study, widely representative, international cohort, phase variables were independently associated with MACE and improved risk stratification for MACE beyond the prediction by perfusion and left ventricular ejection fraction assessment alone. Phase analysis can be obtained fully automatically, without additional radiation exposure or cost to improve MACE risk prediction and, therefore, should be routinely reported for single-photon emission computed tomography-myocardial perfusion imaging studies.

The unfolded protein response (UPR) plays important roles in various cells that have a high demand for protein folding, which are involved in the process of cell differentiation and development. Here, we separately knocked down the three sensors of the UPR in myoblasts and found that PERK knockdown led to a marked transformation in myoblasts from a fusiform to a rounded morphology, which suggests that PERK is required for early myoblast differentiation. Interestingly, knocking down PERK induced reprogramming of C2C12 myoblasts into stem-like cells by altering the miRNA networks associated with differentiation and stemness maintenance, and the PERK-ATF4 signaling pathway transactivated muscle differentiation-associated miRNAs in the early stage of myoblast differentiation. Furthermore, we identified Ppp1cc as a direct target gene of miR-128 regulated by the PERK signaling pathway and showed that its repression is critical for a feedback loop that regulates the activity of UPR-associated signaling pathways, leading to cell migration, cell fusion, endoplasmic reticulum expansion, and myotube formation during myoblast differentiation. Subsequently, we found that the RNA-binding protein ARPP21, encoded by the host gene of miR-128-2, antagonized miR-128 activity by competing with it to bind to the 3' untranslated region (UTR) of Ppp1cc to maintain the balance of the differentiation state. Together, these results reveal the crucial role of PERK signaling in myoblast maintenance and differentiation and identify the mechanism underlying the role of UPR signaling as a major regulator of miRNA networks during early differentiation of myoblasts., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tan, Zhang, Li, Ou, Xie, Chen, Mei, Huang, Zheng and Qu.)

Aims: Single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) stress-only protocols reduce radiation exposure and cost but require clinicians to make immediate decisions regarding rest scan cancellation. We developed a machine learning (ML) approach for automatic rest scan cancellation and evaluated its prognostic safety., Methods and Results: In total, 20 414 patients from a solid-state SPECT MPI international multicentre registry with clinical data and follow-up for major adverse cardiac events (MACE) were used to train ML for MACE prediction as a continuous probability (ML score), using 10-fold repeated hold-out testing to separate test from training data. Three ML score thresholds (ML1, ML2, and ML3) were derived by matching the cancellation rates achieved by physician interpretation and two clinical selection rules. Annual MACE rates were compared in patients selected for rest scan cancellation between approaches. Patients selected for rest scan cancellation with ML had lower annualized MACE rates than those selected by physician interpretation or clinical selection rules (ML1 vs. physician interpretation: 1.4 ± 0.1% vs. 2.1 ± 0.1%; ML2 vs. clinical selection: 1.5 ± 0.1% vs. 2.0 ± 0.1%; ML3 vs. stringent clinical selection: 0.6 ± 0.1% vs. 1.7 ± 0.1%, all P < 0.0001) at matched cancellation rates (60 ± 0.7, 64 ± 0.7, and 30 ± 0.6%). Annualized all-cause mortality rates in populations recommended for rest cancellation by physician interpretation, clinical selection approaches were higher (1.3%, 1.2%, and 1.0%, respectively) compared with corresponding ML thresholds (0.6%, 0.6%, and 0.2%)., Conclusion: ML, using clinical and stress imaging data, can be used to automatically recommend cancellation of rest SPECT MPI scans, while ensuring higher prognostic safety than current clinical approaches., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

The research on the pharmacodynamic substance basis of traditional Chinese medicine(TCM) is a key scientific issue for the inheritance and development of TCM. At present, a large number of remarkable achievements have been made in the field of chemical components in Chinese medicine, however, another important aspect, namely the physical structure and mode of action of the multi-component assembly of TCM, has not been clearly understood and deeply studied. From the bottleneck of restricting material ba-sic research, we objectively analyzed the common cause of the existing problems. Based on the new discoveries and advances of active substances from TCM emerging in recent years, we extracted and summarized the concept of structural Chinese medicine, elaborated the basic ideas, main features and research modes, hoping to provide theoretical and practical references for the study on the pharmacodynamic substance basis and other research fields of TCM.

Background: There are no reports on global research status of gastroenterology and hepatology (GI). This study was conducted to reveal the current global research status and trends in GI., Methods: Articles published during 2009 to 2018 in international GI journals were retrieved from the PubMed database. The top 20 countries by output were determined. The gross domestic product (GDP) of each country was also retrieved to figure out the correlation between outputs in GI and economy. The 5 highest-ranking countries were compared in the number of total articles, articles per capita, articles published in top journals, the accumulated impact factor (IF), and average IF. Total articles and articles per capita of the 5 countries were conducted time-trend analysis. The frequently-used terms in titles and abstracts of articles published in 2009 and 2018 were retrieved to conduct co-occurrence analysis to figure out the change of research highlights in GI., Results: A total of 120,267 articles were included, of which 116,485 articles were from 20 highest-output countries. There was a positive correlation between output and GDP (r = 0.921, P < .001). The USA, Japan, China, Italy, and the UK were the 5 highest-ranking countries. The USA was the largest contributor with 26,215 articles, accounting for 17.4% of the total, but with no significant increasing trend (P = .122). Other 4 countries all showed increasing trends (all P < .001). For articles per capita, Italy ranked 1st among the 5 countries with 1591.0 articles per 10 million. The USA showed a decreasing trend (P = .026), other 4 countries all showed increasing trends (all P < .001). The UK had the highest average IF (6.685). For change of research highlights, it is more inclined to research of endoscopy, inflammatory bowel diseases, and nonalcoholic fatty liver disease., Conclusion: It is delightful that the global research output in GI field would be continuingly increased as the major highest-output countries showed increasing trends. However, the developing countries fell behind both in quantity and quality when compared with developed countries., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: The interval between extracorporeal shock-wave lithotripsy (ESWL) and endoscopic retrograde cholangiopancreatography (ERCP) may cause differences in cannulation and stone removal. This study was to investigate the optimal timing of ERCP after ESWL., Methods: Patients with chronic calcified pancreatitis, who underwent ESWL and subsequent ERCP in Changhai Hospital from February 2012 to February 2015, were retrospectively analyzed. The interval between ESWL and ERCP was used to divide patients into groups A (<12 hours), B (12-36 hours), and C (>36 hours). Cannulation success, stone clearance, and post-ESWL/ERCP complications were compared., Results: A total of 507 patients were enrolled. There were no significant differences regarding the successful cannulation and stone removal rates between the 3 groups. In patients without prior ERCP, the successful cannulation rates were 71.4%, 81.9%, and 90.9% (P = 0.004), and the successful clearance rates were 76.2%, 85.1%, and 90.9% (P = 0.031) for these 3 groups, respectively, showing significant differences. There were no differences in the successful cannulation and stone extraction rates for patients with prior ERCP., Conclusions: The interval between ESWL and ERCP in chronic calcified pancreatitis patients with prior ERCP is not relevant, while delaying endoscopic intervention is recommended in those with native papilla., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Although the number of existing cases of coronavirus disease 2019 (COVID-19) in China has been decreasing since late February 2020, the number of confirmed cases abroad is surging. Improving public knowledge of COVID-19 is critical to controlling the pandemic. This study aimed to determine China's public knowledge of COVID-19 and the attitudes towards control measures., Methods: A cross-sectional study was conducted over 48 h from 22:30 29 February 2020 to 22:30 2 March 2020 based on a self-administered web-based questionnaire. The survey was conducted on the WeChat network. Exponential non-discriminative snowball sampling was applied. The questionnaire was voluntarily completed by WeChat users. The questionnaire covered basic demographic information, public knowledge of the epidemiological and clinical characteristics of COVID-19, psychological state, and attitudes towards the overall control measures. The primary outcome was the China's public knowledge of COVID-19 and the attitudes towards control measures and secondary outcome was the psychological state of the public during this pandemic., Results: The study included 10,905 participants and 10,399 valid questionnaires were included for analysis. Participants with tertiary education, younger participants and healthcare workers had better overall knowledge than other participants (all P < 0.05). Approximately 91.9% of the participants believed in person-to-person transmission and 39.1% believed in animal-to-person transmission. No significant correlation between anxiety and the number of regional existing confirmed cases was found, while participants in Hubei were more anxious than those in other regions. In general, 74.1% of the participants acknowledged the effectiveness of the overall control measures, and the percentage of participants with agreement with the overall control measures was negatively correlated with the number of regional existing confirmed cases (r = - 0.492, P = 0.007)., Conclusions: In conclusion, the survey revealed that the Chinese public had overall good knowledge of COVID-19 except for those indeterminate knowledges. With dynamic changes in the global pandemic situation and more research, further studies should be conducted to explore changes in public knowledge and attitudes towards COVID-19 in the future. The media could be used in a strict and regular manner to publicize knowledge of such pandemics to halt their spread.

Objectives: Using a contemporary, multicenter international single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) registry, this study characterized the potential major adverse cardiovascular event(s) (MACE) benefit of early revascularization based on automatic quantification of ischemia., Background: Prior single-center data reported an association between moderate to severe ischemia SPECT-MPI and reduced cardiac death with early revascularization., Methods: Consecutive patients from a multicenter, international registry who underwent 99m Tc SPECT-MPI between 2009 and 2014 with solid-state scanners were included. Ischemia was quantified automatically as ischemic total perfusion deficit (TPD). Early revascularization was defined as within 90 days. The primary outcome was MACE (death, myocardial infarction, and unstable angina). A propensity score was developed to adjust for nonrandomization of revascularization; then, multivariable Cox modeling adjusted for propensity score and demographics was used to predict MACE., Results: In total, 19,088 patients were included, with a mean follow-up of 4.7 ± 1.6 years, during which MACE occurred in 1,836 (9.6%) patients. There was a significant interaction between ischemic TPD modeled as a continuous variable and early revascularization (interaction p value: 0.012). In this model, there was a trend toward reduced MACE in patients with >5.4% ischemic TPD and a significant association with reduced MACE in patients with >10.2% ischemic TPD., Conclusions: In this large, international, multicenter study reflecting contemporary cardiology practice, early revascularization of patients with >10.2% ischemia on SPECT-MPI, quantified automatically, was associated with reduced MACE., Competing Interests: Funding Support and Author Disclosures This research was supported in part by grant R01HL089765 from the National Heart, Lung, and Blood Institute/National Institutes of Health (principal investigator: Dr. Slomka). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The work was also supported in part by the Miriam and Sheldon Adelson Medical Research Foundation. Dr. R.J.H. Miller received funding support from the Arthur J E Child Fellowship grant. Dr. Einstein has served as a consultant for GE Healthcare, and his institution has received research support from Toshiba America Medical Systems and Roche Medical Systems. Dr. Ruddy has received research grant support from GE Healthcare and Advanced Accelerator Applications. Dr. E. Miller has served as a consultant for GE Healthcare and Bracco Inc.; and he and his institution have received grant support from Bracco Inc. Dr. Dorbala has served as a consultant for GE Healthcare and Bracco Diagnostics; and her institution has received grant support from Astellas. Dr. Di Carli has received research grant support from Spectrum Dynamics and consulting honoraria from Sanofi and GE Healthcare. Dr. Berman participates in software royalties for QPS software at Cedars-Sinai Medical Center; has served as a consultant for GE Healthcare; and his institution has received grant support from HeartFlow. Drs. Slomka participates in software royalties for QPS software at Cedars-Sinai Medical Center; and has received research grant support from Siemens Medical Systems. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

It is urgent to understand the regulatory mechanism of drug resistance in widespread bacterial pathogens. In Mycobacterium tuberculosis, several transcriptional regulators have been found to play essential roles in regulating its drug resistance. In this study, we found that an ArsR family transcription regulator encoded by Rv2642 (CdiR) responds to isoniazid (INH), a widely used anti-tuberculosis (TB) drug. CdiR negatively regulates self and adjacent genes, including arsC (arsenic-transport integral membrane protein ArsC). CdiR directly interacts with INH and Cd(II). The binding of INH and Cd(II) both reduce its DNA-binding activity. Disrupting cdiR increased the drug susceptibility to INH, whereas overexpressing cdiR decreased the susceptibility. Strikingly, overexpressing arsC increased the drug susceptibility as well as cdiR. Additionally, both changes in cdiR and arsC expression caused sensitivity to other drugs such as rifamycin and ethambutol, where the minimal inhibitory concentrations in the cdiR deletion strain were equal to those of the arsC-overexpressing strain, suggesting that the function of CdiR in regulating drug resistance primarily depends on arsC. Furthermore, we found that Cd(II) enhances bacterial resistance to INH in a CdiR-dependent manner. As a conclusion, CdiR has a critical role in directing the interplay between Cd(II) metal ions and drug susceptibility in mycobacteria., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.)

Objective: To explore the application of mixed reality technique for the surgery of oral and maxillofacial tumors., Methods: In this study, patients with a diagnosis of an oral and maxillofacial tumor who were referred to Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology from December 2018 to January 2020 were selected. The preoperative contrast-enhanced computed tomography data of the patients were imported into StarAtlas Holographic Medical Imaging System (Visual 3D Corp., Beijing, China). Three-dimensional (3D) model of tumor and key structures, such as skeleton and vessels were reconstructed to three-dimensionally present the spatial relationship between them, followed with the key structures delineation and preoperative virtual surgical planning. By using mixed reality technique, the real-time 3D model was displayed stereotactically in the surgical site. While keeping sterile during operation, the surgeon could use simple gestures to adjust the 3D model, and observed the location, range, and size of tumor and the key structures adjacent to the tumor. Mixed reality technique was used to assist the operation: 3D model registration was performed for guidance before tumor excision; intraoperative real-time verification was performed during tumor exposure and after excision of the tumor. The Likert scale was used to evaluate the application of mixed reality technique after the operation., Results: Eight patients underwent mixed reality assisted tumor resection, and all of them successfully completed the operation. The average time of the 3D model registration was 12.0 minutes. In all the cases, the surgeon could intuitively and three-dimensionally observe the 3D model of the tumor and the surrounding anatomical structures, and could adjust the model during the operation. The results of the Likert scale showed that mixed reality technique got high scores in terms of perceptual accuracy, helping to locate the anatomical parts, the role of model guidance during surgery, and the potential for improving surgical safety (4.22, 4.19, 4.16, and 4.28 points respectively). Eight patients healed well without perioperative complications., Conclusion: By providing real-time stereotactic visualization of anatomy of surgical site and guiding the operation process through 3D model, mixed reality technique could improve the accuracy and safety of the excision of oral and maxillofacial tumors.

Predatory hunting is an important approach for animals to obtain valuable nutrition and energy, which critically depends on heightened arousal. Yet the neural substrates underlying predatory hunting remain largely undefined. Here, we report that basal forebrain (BF) GABAergic neurons play an important role in regulating predatory hunting. Our results showed that BF GABAergic neurons were activated during the prey (cricket)-hunting and food feeding in mice. Optogenetic activation of BF GABAergic neurons evoked immediate predatory-like actions to both artificial and natural preys, significantly reducing the attack latency while increasing the attack probability and the number of killed natural prey (crickets). Similar to the effect of activating the soma of BF GABAergic neurons, photoactivation of their terminals in the ventral tegmental area (VTA) also strongly promotes predatory hunting. Moreover, photoactivation of GABAergic BF - VTA pathway significantly increases the intake of various food in mice. By synchronous recording of electroencephalogram and electromyogram, we showed that photoactivation of GABAergic BF - VTA pathway induces instant arousal and maintains long-term wakefulness. In summary, our results clearly demonstrated that the GABAergic BF is a key neural substrate for predatory hunting, and promotes this behavior through GABAergic BF - VTA pathway., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background/aims: This study evaluates the association between the eradication of Helicobacter pylori (H. pylori) and gastroesophageal reflux disease (GERD)., Materials and Methods: Relevant studies were identified by conducting literature search in PubMed, Cochrane, Embase, CNKI, VANFUN, and VIP databases. The prevalence rates of gastroesophageal reflux, heartburn, epigastric pain, and nausea were extracted from the identified research articles and were used in meta-analysis of relative risks (RR) to achieve an overall effect size of the relationship between H. pylori eradication and GERD., Results: A total of 19 randomized controlled trials were included in this meta-analysis. The prevalence of gastroesophageal reflux was significantly higher in patients with H. pylori eradication compared with patients without it (RR: 1.54, 95% CI: 1.06-2.24; p=0.02). A subgroup analysis did not identify any significant difference in GERD prevalence in studies conducted outside China (RR: 1.62, 95% CI: 0.98-2.68) or in China (RR: 1.30, 95% CI: 0.76-2.22). There were no significant differences in heartburn (RR: 1.03, 95% CI: 0.88-1.20), epigastric pain (RR: 0.98, 95% CI: 0.13-7.56), or nausea (RR: 0.44, 95% CI: 0.07-2.72) risk between patients with and without H. pylori eradication., Conclusion: Eradication of H. pylori infection is found to be associated with GERD, although regional differences may exist in the prevalence. Well-designed studies especially those with stratification of patients' basic conditions are needed to seek refined evidence of the association between H. pylori eradication and the GERD.

Objectives: The 2019 novel coronavirus disease (COVID-19) pandemic is the biggest public health crises in the 21st century. While most patients infected with the COVID-19 virus have no to moderate symptoms, there is currently limited clinical information about these patients. Methods: In this study, we retrospectively investigated 41 patients infected with the COVID-19 virus in Nanchang, Jiangxi province, China, from February 4 to March 2, 2020. Nanchang is about 260 km southeast of Wuhan, the initial epicenter of the COVID-19 pandemic. We retrieved information on patient demographics, physical examination results, epidemiology, clinical manifestations, underlying conditions, laboratory analyses, radiological images, and treatment outcomes. Results: Most patients (70.7%) had a history of close contact with patients with confirmed COVID-19, and 16 patients (39.0%) showed a high degree of family clustering. All 41 patients had no to moderate symptoms. The median age was 39.9 years and common symptoms of illness were fever (69.2%), cough (65.4%), and fatigue (19.2%). The dominant patient group was middle-aged women, with hypertension (14.6%) and chronic liver disease (12.2%) as the most frequent underlying conditions. All patients recovered, with the mean time of viral nucleic acid clearance at 10.6 days. Chest CT scans presented ground-glass opacities in 53.7% of patients while 26.8% had normal CT images. Laboratory results showed that lymphocyte counts, lymphocyte percentages, ESR, CRP, IgG, Fib, and cytokines were correlated to patients' conditions. Approximately 60-90% of patients had abnormally high levels of cytokines IL-4, IL-6, IL-10, and/or TNF-α. Conclusions: Our results showed variable clinical and laboratory presentations among this group of patients infected with the COVID-19 virus. Though all 41 patients recovered, our results suggest that cytokine levels and other biochemical indicators should be monitored for patients infected with the COVID-19 virus showing no to moderate symptoms to ensure quick access for critical medical attention, if needed., (Copyright © 2020 Hong, Hu, Zhong, Zhu, Hang, Fang, Sun, Huang, Xu and Chen.)

Objective: The aim of the study was to investigate the global research levels in chronic pancreatitis (CP) fields., Methods: The term "chronic pancreatitis" was used to retrieve articles published between 2009 and 2018 from the Web of Science database. The 15 highest-output countries' gross domestic product was retrieved to analyze the correlation between output and economic development. The 5 top-ranking countries were compared in quantity and quality. The frequently used terms of all articles were retrieved to conduct co-occurrence analysis to reveal research highlights for CP., Results: There were 6094 articles included and 6007 articles were from 15 highest-output countries. There was a positive correlation between output and gross domestic product (r = 0.928, P < 0.001). The United States, China, and Japan had increasing trends in total output (P = 0.022, P < 0.001, and P = 0.021, respectively). China and Japan had increasing trends in output per capita (P < 0.001 and P = 0.023). However, in average impact factor, all 5 countries did not show increasing trends (all P > 0.05). For research highlights, mass lesion and autoimmune pancreatitis were the notable aspects., Conclusions: The global output for CP will continue increasing and research quality will be stable.

The glutamatergic lateral hypothalamus (LH) has been implicated in a variety of behaviors, such as evasion and feeding, while its role in defensive behaviors and relevant neurocircuits remains unclear. Here, we demonstrated that the glutamatergic LH is a critical structure regulating defensive behaviors. Trimethylthiazole (TMT), the odor of mice predator, significantly increased c-Fos expression in the LH. Using fiber photometry technology, we found that TMT exposure increased the activity of LH glutamatergic neurons. Selective activation of LH glutamatergic neurons with optogenetics and chemogenetics promoted a series of defense-related behaviors, including fleeing, avoidance, and hiding, while selective inhibition of LH glutamatergic neurons suppressed the avoidance provoked by TMT. Activation of both the glutamatergic LH terminals in the hypothalamic paraventricular nucleus (PVN) and the glutamatergic projection from the basolateral amygdala (BLA) to the LH elicited defensive behaviors. Finally, by combining the viral-mediated retrograde tracing with anterograde activation, we found that PVN-projecting glutamatergic neurons in the LH were activated by BLA glutamatergic inputs. Taken together, our results illustrate that the glutamatergic LH is a pivotal relay of defensive behaviors and possibly promotes these behaviors through the BLA→LH→PVN pathway., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Kinetoplastid flagellates are known for several unusual features, one of which is their complex mitochondrial genome, known as kinetoplast (k) DNA, composed of mutually catenated maxi- and minicircles. Trypanosoma lewisi is a member of the Stercorarian group of trypanosomes which is, based on human infections and experimental data, now considered a zoonotic pathogen. By assembling a total of 58 minicircle classes, which fall into two distinct categories, we describe a novel type of kDNA organization in T. lewisi. RNA-seq approaches allowed us to map the details of uridine insertion and deletion editing events upon the kDNA transcriptome. Moreover, sequencing of small RNA molecules enabled the identification of 169 unique guide (g) RNA genes, with two differently organized minicircle categories both encoding essential gRNAs. The unprecedented organization of minicircles and gRNAs in T. lewisi broadens our knowledge of the structure and expression of the mitochondrial genomes of these human and animal pathogens. Finally, a scenario describing the evolution of minicircles is presented., (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)