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Two fusidane-type active compounds ( 6 and 7 ) and five new ones ( 1-5 ), along with other nine known compounds ( 8-16 ) were isolated from the metabolites of Schizophyllum commune MST7-3. Their structures were elucidated on the basis of spectroscopic analysis. The absolute configurations of compounds 2 and 3 were established by Mosher's method and optical rotation. Compounds 6 and 7 showed significant antibacterial activities against Stenotrophomonas maltophilia with MIC values of 4 μg/mL and 16 μg/mL, respectively.

Family history (FH) of late-onset Alzheimer's disease (AD) is associated with changes in several cerebrospinal fluid (CSF) biomarkers in cognitively normal individuals. However, potential changes in plasma biomarkers remain unknown. This study aimed to evaluate potential plasma biomarkers and their correlation in cognitively normal adult children (AC) and to compare this data with their AD parents and unrelated non-demented controls (NC). Participants with dementia due to AD, their AC and NC were recruited. Plasma samples were assessed for amyloid beta (Aβ) 1-42 , Aβ 1-40 , total tau (T-tau) and phosphorylated tau (P-tau). Kruskal-Wallis test was used for the comparison of this data between the three groups. Spearman rank correlation was used for evaluation of the correlations between Aβ 1-40 and Aβ 1-42 , and T-tau and P-tau in the AD and AC groups. A total of 99 subjects completed the assessment (30 had AD; 38 were AC group; and 31 were NC). Compared with the NC group, there were significantly higher levels of Aβ 1-40 , P-tau, and P-tau/T-tau ratio, and lower levels of Aβ 1-42 and Aβ 1-42 /Aβ 1-40 ratio in the AD and AC groups. The correlation between the level of Aβ 1-42 and Aβ 1-40 and level of T-tau and P-tau was only observed in the AC but not in the AD group. AC of AD parents demonstrate some indicators of AD like their parents. Disruption to the correlation between Aβ and tau in AD may be a biomarker for the development of AD in AC, which should be examined in a longitudinal cohort., 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 Huang, Chen, Chuu, Li, Hour and Yang.)

Excess sludge management is a restrictive factor for the development of municipal wastewater treatment plants. The addition of metabolic uncouplers has been proven to be effective in sludge reduction. However, the long-term effect of metabolic uncoupler o-chlorophenol (oCP) on the biological wastewater treatment system operated in anaerobic-oxic mode is still unclear. To this end, two parallel reactors operated in anaerobic-oxic mode with and without 10 mg/L of oCP addition were investigated for 91 days. The results showed that 56.1 ± 2.3% of sludge reduction was achieved in the oCP-added system, and the nitrogen and phosphorus removal ability were negatively affected. Dosing oCP stimulated the formation of microbial products and increased the DNA concentration, but resulted in a decrease in the electronic transport activity of activated sludge. Microbial community analysis further demonstrated that a significant reduction of bacterial richness and diversity occurred after oCP dosing. However, after stopping oCP addition, the pollutant removal ability of activated sludge was gradually increased, but the sludge yield, as well as species richness and diversity, did not recover to the previous level. This study will provide insightful guidance on the long-term application of metabolic uncouplers in the activated sludge system., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

(1) Background: Strains HL1 and M1, isolated from kefir grains, have been tentatively identified, based on their partial 16S rRNA gene sequences, as Lactobacillus kefiranofaciens . The two strains demonstrated different health benefits. Therefore, not only the genetic factors exerting diverse functionalities in different L. kefiranofaciens strains, but also the potential niche-specific genes and pathways among the L. kefiranofaciens strains, should be identified. (2) Methods: Phenotypic and genotypic approaches were employed to identify strains HL1 and M1 at the subspecies level. For the further characterization of the probiotic properties of both strains, comparative genomic analyses were used. (3) Results: Both strains were identified as L. kefiranofaciens subsp. kefirgranum . According to the COG function category, dTDP-rhamnose and rhamnose-containing glycans were specifically detected in the L. kefiranofaciens subsp. Kefirgranum genomes. Three unique genes ( epsI , epsJ , and epsK ) encoding glycosyltransferase in the EPS gene cluster, and the ImpB/MucB/SamB family protein encoding gene were found in HL1 and M1. The specific ability to degrade arginine via the ADI pathway was found in HL1. The presence of the complete glycogen metabolism ( glg ) operon in the L. kefiranofaciens strains suggested the importance of glycogen synthesis to enable colonization in kefir grains and extend survival under environmental stresses. (4) Conclusions: The obtained novel information on the potential genes and pathways for polysaccharide synthesis and other functionalities in our HL1 and M1 strains could be applied for further functionality predictions for potential probiotic screening.

Background: Acute ST-elevation myocardial infarction (STEMI) elicits a robust cardiomyocyte death and inflammatory responses despite timely revascularization., Objectives: This phase 1, open-label, single-arm, first-in-human study aimed to assess the safety and efficacy of combined intracoronary (IC) and intravenous (IV) transplantation of umbilical cord-derived mesenchymal stem cells (UMSC01) for heart repair in STEMI patients with impaired left ventricular ejection fraction (LVEF 30-49%) following successful reperfusion by percutaneous coronary intervention., Methods: Consenting patients received the first dose of UMSC01 through IC injection 4-5 days after STEMI followed by the second dose of UMSC01 via IV infusion 2 days later. The primary endpoint was occurrence of any treatment-related adverse events and the secondary endpoint was changes of serum biomarkers and heart function by cardiac magnetic resonance imaging during a 12-month follow-up period., Results: Eight patients gave informed consents, of whom six completed the study. None of the subjects experienced treatment-related serious adverse events or major adverse cardiovascular events during IC or IV infusion of UMSC01 and during the follow-up period. The NT-proBNP level decreased (1362 ± 1801 vs. 109 ± 115 pg/mL, p = 0.0313), the LVEF increased (52.67 ± 12.75% vs. 62.47 ± 17.35%, p = 0.0246), and the wall motion score decreased (26.33 ± 5.57 vs. 22.33 ± 5.85, p = 0.0180) at the 12-month follow-up compared to the baseline values. The serial changes of LVEF were 0.67 ± 3.98, 8.09 ± 6.18, 9.04 ± 10.91, and 9.80 ± 7.56 at 1, 3, 6, and 12 months, respectively as compared to the baseline., Conclusion: This pilot study shows that combined IC and IV transplantation of UMSC01 in STEMI patients with impaired LVEF appears to be safe, feasible, and potentially beneficial in improving heart function. Further phase 2 studies are required to explore the effectiveness of dual-route transplantation of UMSC01 in STEMI patients., Competing Interests: C-HT was the founder of Ever Supreme Bio Technology. W-CS, D-YC, K-CC, and L-BJ were stockholders of the Ever Supreme Bio Technology. W-CS was employed by Ever Supreme Bio Technology and China Medical University Hospital. C-TH, C-KT, L-TC, and C-LC were employed by Ever Supreme Bio Technology. 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 © 2022 Hsiao, Lin, Shyu, Ho, Lu, Chang, Wang, Chen, Lu, Wu, Li, Lin, Tseng, Su, Hsu, Tsai, Chiu, Chen, Lin, Hu, Cho, Tsai, Chang and Jeng.)

Background: Pouchitis is the common postoperative complication of ulcerative colitis (UC) and is also considered as inflammatory bowel disease. The aim was to investigate the microbiological and transcriptional differences between the two illnesses., Methods: Eighty-five participants were enrolled (37 UC, 15 healthy UC pouches, 15 pouchitis and 18 healthy volunteers) and stool samples were collected. Microbial populations were analyzed by pyrosequencing of 16S ribosomal DNA. Furthermore, transcriptome data of 119 UC and 28 pouch patients were obtained from two data sets for bioinformatics analysis., Results: The results of gut microbiota community analysis showed that with aggravation of UC, intestinal microorganisms were characterized by a gradual decreased in diversity and numbers of butyrate-producing bacteria and Bacteroides . Besides, in addition to the decrease of probiotics, the proliferation of Escherichia-Shigella and Ruminococcus gnavus was observed in pouchitis which is related to multiple infection pathways. The function enrichment of differential expression genes and hub genes, as well as the immunological condition was shown to be distinct using transcriptome bioinformatics analysis between UC and pouchitis. A stronger immune response occurs in UC and may be associated with high expression of tumor necrosis factor and interleukin, while multiple hub genes such as CDK1 in pouchitis are associated with cell cycle regulation., Conclusions: The characteristics of gut microbiota disturbance and transcriptome alteration in UC and pouchitis are different. Our findings suggested that pouchitis may have a unique pathogenesis which was separated from UC.

Background and objective Although hospitalization is required for only a minority of those infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the high rates of morbidity and mortality among these patients have led researchers to focus on the predictors of admission and adverse outcomes in the inpatient population. However, there is scarce data on the clinical trajectory of individuals symptomatic enough to present for emergency care, but not sick enough to be admitted. In light of this, we aimed to examine the symptomatology, emergency department (ED) revisits, and hospitalization of coronavirus disease 2019 (COVID-19) outpatients after discharge from the ED. Methods Adult patients with COVID-19 infection were prospectively enrolled after discharge from the ED between May and December 2020. Patients were followed up longitudinally for 14 days via phone interviews designed to provide support and information and to track symptomatology, ED revisits, and hospitalization. Results A volunteer, medical student-run program enrolled 199 COVID-19 patients discharged from the ED during the first nine months of the pandemic. Of the 176 patients (88.4%) who completed the 14-day protocol, 29 (16.5%) had a second ED visit and 17 (9.6%) were admitted, 16 (9%) for worsening COVID-19 symptoms. Age, male sex, comorbid illnesses, and self-reported dyspnea, diarrhea, chills, and fever were associated with hospital admission for patients with a subsequent ED visit. For those who did not require admission, symptoms generally improved following ED discharge. Age >65 years and a history of cardiovascular disease (CVD) were associated with a longer duration of cough, but generally, patient characteristics and comorbidities did not significantly affect the overall number or duration of symptoms. Conclusions Nearly one in five patients discharged from the ED with COVID-19 infection had a second ED evaluation during a 14-day follow-up period, despite regular phone interactions aimed at providing support and information. More than half of them required admission for worsening COVID-19 symptoms. Established risk factors for severe disease and self-reported persistence of certain symptoms were associated with hospital admission, while those who did not require hospitalization had a steady improvement in symptoms over the 14-day period., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Bayly et al.)

The purpose of this study was to investigate whether ameloblastoma with a high likelihood of recurrence can be predicted using random forest model, a machine learning algorithm. Data were collected from patients treated for ameloblastoma between 1999 and 2019 at the University of Hong Kong. Fourteen clinical parameters were used to grow the decision trees to classify patients with or without ameloblastoma recurrence in the follow-up period. The random forest algorithm was computed 100 times in the training cohort (n = 100) and verified in the testing cohort (n = 50). The receiver operating characteristic curve (ROC) and area under the curve (AUC) were used as the performance measurement of separability. One hundred and fifty patients (76 female, 74 male) were recruited, with a mean follow-up time of 103 months. Recurrence occurred in a total of 25 cases (16.7%) over the 20-year period. The AUC were calculated for the median and mean ROC curves; these were 0.777 and 0.825, respectively. The results showed that random forest model was able to predict recurrence of ameloblastoma with reliable accuracy. The four most important variables influencing ameloblastoma recurrence were the time elapsed from treatment, initial surgical treatment, tumour size, and radiographic presentation. This study provides insights into the detection of high-risk patient groups to monitor recurrence. Further application of random forest to other diseases could greatly benefit clinical decisions., (Copyright © 2021 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Folic acid, served as dietary supplement, is closely linked to one-carbon metabolism and methionine metabolism. Previous clinical evidence indicated that folic acid supplementation displays dual effect on cancer development, promoting or suppressing tumor formation and progression. However, the underlying mechanism remains to be uncovered. Here, we report that high-folate diet significantly promotes cancer development in mice with hepatocellular carcinoma (HCC) induced by DEN/high-fat diet (HFD), simultaneously with increased expression of methionine adenosyltransferase 2A (gene name, MAT2A; protein name, MATIIα), the key enzyme in methionine metabolism, and acceleration of methionine cycle in cancer tissues. In contrast, folate-free diet reduces MATIIα expression and impedes HFD-induced HCC development. Notably, methionine metabolism is dynamically reprogrammed with valosin-containing protein p97/p47 complex-interacting protein (VCIP135) which functions as a deubiquitylating enzyme to bind and stabilize MATIIα in response to folic acid signal. Consistently, upregulation of MATIIα expression is positively correlated with increased VCIP135 protein level in human HCC tissues compared to adjacent tissues. Furthermore, liver-specific knockout of Mat2a remarkably abolishes the advocating effect of folic acid on HFD-induced HCC, demonstrating that the effect of high or free folate-diet on HFD-induced HCC relies on Mat2a. Moreover, folate and multiple intermediate metabolites in one-carbon metabolism are significantly decreased in vivo and in vitro upon Mat2a deletion. Together, folate promotes the integration of methionine and one-carbon metabolism, contributing to HCC development via hijacking MATIIα metabolic pathway. This study provides insight into folate-promoted cancer development, strongly recommending the tailor-made folate supplement guideline for both sub-healthy populations and patients with cancer expressing high level of MATIIα expression., (© 2022. The Author(s).)

Backgrounds and Purpose: The theory of "entero-pulmonary axis" proves that pneumonia leads to gut microbiota disturbance and Treg/Th17 immune imbalance. This study is aimed to explore the potential mechanism of fecal microbiota transplantation (FMT) in the treatment of Pseudomonas aeruginosa pneumonia, in order to provide new insights into the treatment of pneumonia., Methods: Pseudomonas aeruginosa and C57/BL6 mice were used to construct the acute pneumonia mouse model, and FMT was treated. Histopathological changes in lung and spleen were observed by HE staining. The expression of CD25, Foxp3 and IL-17 was observed by immunofluorescence. The proportion of Treg and Th17 cells was analyzed by flow cytometry. Serum IL-6, LPS, and IFN-γ levels were detected by ELISA. The expression of TNF-α, IFN-γ, IL-6, IL-2, Foxp3, IL-17, IL-10, and TGFβ1 in lung tissue homogenate was detected by qRT-PCR. 16S rRNA sequencing and non-targeted metabolomics were used to analyze gut microbiota and metabolism., Results: Pseudomonas aeruginosa caused the decrease of body weight, food and water intake, lung tissue, and spleen injury in mice with pneumonia. Meanwhile, it caused lung tissue and serum inflammation, and Treg/Th17 cell imbalance in mice with pneumonia. Pseudomonas aeruginosa reduced the diversity and number of gut microbiota in pneumonia mice, resulting in metabolic disorders, superpathway of quinolone and alkylquinolone biosynthesis. It also led to the decrease of 2-heptyl-3-hydroxy-4(1H)-quinolone biosynthesis, and the enrichment of Amino sugar and nucleotide sugar metabolism. FMT with or without antibiotic intervention restored gut microbiota abundance and diversity, suppressed inflammation and tissue damage, and promoted an immunological balance of Treg/Th17 cells in mice with pneumonia. In addition, FMT inhibited the aerobactin biosynthesis, 4-hydroxyphenylacetate degradation, superpathway of lipopolysaccharide biosynthesis and L-arabinose degradation IV function of microbiota, and improved amino sugar and nucleotide sugar metabolism., Conclusions: FMT restored the Treg/Th17 cells' balance and improved inflammation and lung injury in mice with Pseudomonas aeruginosa pneumonia by regulating gut microbiota disturbance and metabolic disorder., 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 Wen, Shi, Kong, Li, Li, Jiang, Zhang and Zhou.)

Aim: To compare the validity of DIAGNOdent pen™ 2190 and clinical photographs in the diagnosis (presence or absence) and assessment of white spot lesions (WSLs) during multi-bracketed fixed orthodontic treatment., Methods: A total of 1607 readings from 99 patients were obtained using DIAGNOdent pen™ 2190, clinical photographs, and visual assessment criteria to assess WSLs at 6 -, 12- and 18 months after bonding of brackets. Receiver operating characteristic curves were constructed, and areas under the curve (AUC) were calculated to assess the presence or absence of WSLs and distinguish the severity of WSLs as slight or severe. Sensitivities, specificities, and AUC were calculated for outcomes at an alpha of 0.05 and 95% confidence intervals (CIs)., Results: The values of sensitivity and specificity of DIAGNOdent pen™ 2190 were found to be 0.78 and 0.83, respectively, to distinguish presence/absence of WSLs with good accuracy (AUC= 0.855; 95% CI: 0.820-0.889) and for digital photographs, accuracy was excellent (AUC= 0.973, 95% CI: 0.956-0.991) with sensitivity and specificity of 0.96 and 0.99, respectively. However, the accuracy of DIAGNOdent pen™ 2190 was poor (AUC= 0.543, 95% CI: 0.418-0.668) in delineating slight and severe WSLs with a sensitivity of 0.31 and specificity of 0.83; while the values of sensitivity and specificity for distinguishing slight or severe lesions for clinical photographs were 0.96 and 0.99, respectively with excellent accuracy (AUC=0.978, 95% CI: 0.936-1.000)., Conclusions: Clinical photographs had better validity than DIAGNOdent pen™ 2190 in diagnosis and assessment of severity of demineralized lesions during multi-bracketed fixed orthodontic treatment., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Ivelayini sp. nov. , is described from Guangdong, China based on morphological characters and molecular data. Adults, including genitalia and wing venation, and pupa are illustrated and compared to those of similar species. A key to Chinese Ivela species is provided. Assignment of the new species to Ivela Swinhoe is based primarily on a molecular phylogenetic analysis and is corroborated by morphology. Life histories of I.yini and Dendrophlepssemihyalina Hampson are discussed., (Lin-Zhe Xie, Kun-Yuan Li, Liu-Sheng Chen, Hou-Shuai Wang.)

Background: Most health insurance organizations reimbursed both video and audio-only (i.e., phone) visits during the COVID-19 pandemic, but may discontinue phone visit coverage after the pandemic. The impact of discontinuing phone visit coverage on various patient subgroups is uncertain., Objective: Identify patient subgroups that are more probable to access telehealth through phone versus video., Design: Retrospective cohort., Patients: All patients at a U.S. academic medical center who had an outpatient visit that was eligible for telehealth from April through June 2020., Main Measures: The marginal and cumulative effect of patient demographic, socioeconomic, and geographic characteristics on the probability of using video versus phone visits., Key Results: A total of 104,204 patients had at least one telehealth visit and 45.4% received care through phone visits only. Patient characteristics associated with lower probability of using video visits included age (average marginal effect [AME] -6.9% for every 10 years of age increase, 95%CI -7.8, -4.5), African-American (AME -10.2%, 95%CI -11.4, -7.6), need an interpreter (AME -19.3%, 95%CI -21.8, -14.4), Medicaid as primary insurance (AME -12.1%, 95%CI -13.7, -9.0), and live in a zip code with low broadband access (AME -7.2%, 95%CI -8.1, -4.8). Most patients had more than one factor which further reduced their probability of using video visits., Conclusions: Patients who are older, are African-American, require an interpreter, use Medicaid, and live in areas with low broadband access are less likely to use video visits as compared to phone. Post-pandemic policies that eliminate insurance coverage for phone visits may decrease telehealth access for patients who have one or more of these characteristics., (© 2021. Society of General Internal Medicine.)

Adverse events affecting Black patients, including skin hyperpigmentation, may be overlooked using existing clinical trial data on lenalidomide. The objective of this systematic review is to characterize the representation of Black participants and rate of skin hyperpigmentation in clinical trials. In this systematic review and pooled analysis of 21 clinical trials comprising 4539 participants, the proportion of Black participants in trials (6.9%, n = 315) was significantly less than the multiple myeloma population (p < 0.001). The rate of skin hyperpigmentation (0.066%, n = 3) and all skin changes (6.4%, n = 291) was significantly less compared to a 40.8% incidence in a recent retrospective study (p. <0.001). Among participants undergoing treatment with lenalidomide for multiple myeloma, Black patients were underrepresented and the adverse event of skin hyperpigmentation was underreported. Fair representation of Black patients in clinical trials is needed to better describe this adverse event and other events that may be underreported., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Ficus religiosa L., known as bodhi tree, is an ornamental tree and widely planted as an avenue and roadside tree due to ovate-rounded leaves with narrow, elongated tips. During 2018-2021, circular to oval-shaped leaf spots with pale white centers and brown-black edges surrounded by a chlorotic halo were observed on the leaves of more than 200 bodhi trees all year round in a park in Zhanjiang, Guangdong (N 21°15'22.29''; E110°23'1.03''). The leaf disease incidences were usually 15-80%, in severe cases, up to 100% in autumn and winter every year, and some trees shed all leaves(Fig S1). Repeated annual defoliation may weaken the tree and decrease the aesthetic value in the landscape. Diseased tissues (5 × 5 mm) of five symptomatic infected leaves were surface sterilized in 3% hydrogen peroxide solution for 3 min, rinsed thrice with sterile water, plated on potato dextrose agar (PDA) amended with ampicillin (50mg/L), and incubated at 25-28 ℃ in the dark for 3-7 days. Five strains with similar morphology were obtained by transferring hyphal tips of the colonies to fresh PDA and further isolating by single spore method. Fungal colonies were flat and spreading, with sparse, white aerial mycelium, and black pycnidial conidiomata semi-immersed in PDA after 30-days incubation at 25-28 ℃ in dark. Conidiophores were hyaline and α-conidia were single-celled, oval to fusiform, guttulate, 5.3 × 2.5 μm (n>50), similar to Diaporthe sp. (Crous et al. 2015), but no β and γ -conidia were observed. The internal transcribed spacer(ITS), large subunit ribosomal RNA gene(LSU), calmodulin (CAL) and β-tubulin(TUB) gene regions of a representative strain were amplified using specific primers reported by White et al. (1990), Gao et al (2017) and Gomes et al (2013), and submitted to GenBank (ITS: OM200852, LSU: OM228732, CAL: OM244761, TUB: OM244760). NCBI Blastn showed above 99% identity to D. tulliensis (anamorph: Phomopsis heveicola ) isolates of ITS (MT974186, MN393590 and KX457967), LSU (KR936131), CAL (MW759801), and TUB (KR936132 and MN399886), respectively (Crous et al. 2015; Huang et al. 2021; Gong et al. 2020; Bai et al. 2017). Based on the concatenated ITS, CAL, and TUB, a Maximum Likelihood phylogenetic analyses using MEGA 10.1.8 clustered the fungus with D. tulliensis in a clade with a 93% bootstrap support(Fig S2). Therefore, the fungus was identified as D. tulliensis based on morpho- molecular characteristics. Healthy detached leaves were sanitized thrice with 70% alcohol, and rinsed with sterile water. PDA plugs with actively growing 10-days-old mycelium were placed on predetermined sites, put into a sealed box with above 80% relative humidity and incubated at room temperature (25-28℃). Each isolate was inoculated at 25 needle-wounded and unwounded sites, PDA plugs without mycelium served as controls. Symptomatic spots appeared on all wounded leaves by 7 days post-inoculation (dpi) and on all unwounded leaves by 12 dpi. No symptoms appeared on controlled leaves. Pure cultures were recovered from inoculated leaves and showed identical morpho-molecular criteria to the original isolates. More than 70 pathogenic fungi are known to cause diseases on F. religiosa while there is no record of D. tulliensis infecting bodhi according to the U.S. National Fungus Collection (Farr and Rossman 2022). This report could provide basic understanding and alerting role for horticulturist in daily management.

(1) Background: We aimed to isolate and identify potential next-generation probiotics (NGP) by investigating the interrelationships between gastrointestinal microbiota and diarrhea in preruminant Holstein calves. (2) Material and methods: Twenty preruminant Holstein calves were divided into healthy and diarrheic groups after the combination outcomes of veterinary diagnosis and fecal scores. The fecal microbiome, plasma cytokines, plasma immunoglobulin (Ig) G and haptoglobin were analyzed. The potential probiotic bacteria were identified by comparing the microbiota difference between healthy and diarrheic calves and correlation analysis with fecal scores and inflammatory markers. The identified bacteria were also isolated for further evaluation for antimicrobial activities and immunoregulatory effects. (3) Results: Microbiota analysis suggested that Ruminococcaceae&#95;UCG&#95;014 , Bifidobacterium and Pseudoflavonifractor positively correlated with bovine IgG and negatively correlated with fecal score; inflammatory factors, bovine HP, and IL-8 were classified as beneficial bacteria contributing to the health of the calves. The alternation of gut microbial composition also induced changes in the functional gene enrichment of gut microbiota in calves. The gathering of microbiomic data strongly indicated the possible beneficial effects of Bifidobacterium longum subsp. longum , expected to develop as NGP. After isolation and evaluation of the potential functionality in vitro, two specific bifidobacterial strains demonstrated antimicrobial activities and immunoregulatory effects. (4) Conclusions: The results provide a new probiotic searching approach for preventing gastrointestinal disorders in preruminant calves. Further animal study is necessary to verify the results.

Background: The characteristics of infective endocarditis (IE) in Asians are poorly understood. Therefore, we aim to describe the epidemiological trends and clinical features of IE in Hong Kong., Methods: All patients with incident IE from 2002-2019 in a territory-wide clinical database in Hong Kong were identified. We studied the age- and sex-adjusted and one-year mortality of IE between 2002 and 2019 and identified significant contributors to 1-year all-cause death using the attributable fraction. We used propensity score and inverse propensity of treatment weighting to study the association of surgery with mortality., Findings: A total of 5139 patients (60.4 ± 18.2years, 37% women) were included. The overall incidence of IE was 4.9 per 100,000 person-year, which did not change over time ( P  = 0.17). Patients in 2019 were older and more comorbid than those in 2002. The one-year crude mortality rate was 30% in 2002, which did not change significantly over time ( P  = 0.10). Between 2002 and 2019, the rate of surgery increased and was associated with a 51% risk reduction in 1-year all-cause mortality (Hazard Ratio 0.49 [0.28-0.87], P  = 0.015). Advanced age (attributable fraction 19%) and comorbidities (attributable fraction 15%) were significant contributors to death., Interpretation: The incidence of IE in Hong Kong did not change between 2002 and 2019. Patients with IE in 2019 were older and had more comorbidities than those in 2002. Mortality of IE remains persistently high in Hong Kong. Together, these data can guide public health strategies to improve the outcomes of patients with IE., Funding: This work was supported by Sanming Project of Medicine in Shenzhen, China [No. SZSM201911020] and HKU-SZH Fund for Shenzhen Key Medical Discipline [No. SZXK2020081]., Competing Interests: JT received speaker fees from Boehringer Ingelheim, Daiichi Sankyo and Roche diagnostics, consultancy fees from Us2.ai, is Stockholder of Us2.ai and owns a patent (US-10702247-B2) unrelated to the present work. CSPL is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from Bayer and Roche Diagnostics; has served as consultant or on the Advisory Board/ Steering Committee/ Executive Committee for Abbott, Actelion, Allysta Pharma, Amgen, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Darma Inc., EchoNous Inc, Impulse Dynamics, Ionis Pharmaceutical, Janssen Research & Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, Prosciento Inc, Radcliffe Group Ltd., Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics and Us2.ai; and serves as co-founder & non-executive director of Us2.ai. All other authors declare no conflict of interest., (© 2022 The Authors.)

The cardiac conduction system (CCS) comprises critical components responsible for the initiation, propagation, and coordination of the action potential. Aberrant CCS development can cause conduction abnormalities, including sick sinus syndrome, accessory pathways, and atrioventricular and bundle branch blocks. Gene Ontology (GO; http://geneontology.org/) is an invaluable global bioinformatics resource which provides structured, computable knowledge describing the functions of gene products. Many gene products are known to be involved in CCS development; however, this information is not comprehensively captured by GO. To address the needs of the heart development research community, this study aimed to describe the specific roles of proteins reported in the literature to be involved with CCS development and/or function. 14 proteins were prioritized for GO annotation which led to the curation of 15 peer-reviewed primary experimental articles using carefully selected GO terms. 152 descriptive GO annotations, including those describing sinoatrial node and atrioventricular node development were created and submitted to the GO Consortium database. A functional enrichment analysis of 35 key CCS development proteins confirmed that this work has improved the in-silico interpretation of this CCS dataset. This work may improve future investigations of the CCS with application of high-throughput methods such as genome-wide association studies analysis, proteomics, and transcriptomics., 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 Chloe Li, Cook and Lovering.)

A systematic review is conducted to identify effective interventions that improved adherence to antihypertensive drugs among patients with coronary heart diseases (CHDs). Primary studies designed to measure interventions to improve adherence on antihypertensive drugs in patients with CHD were included. Three online databases, COCHRANE, EMBASE and MEDLINE, were searched for primary studies published in English from 2005 to 2019. Studies were screened independently for eligibility. Cochrane risk-of-bias tool and the Newcastle-Ottawa Scale were used for quality assessment of randomised controlled trials (RCTs) and non-randomised studies, respectively. Of the 2000 entries identified, seven articles, including one cross-sectional study and six RCTs, met the inclusion criteria and were reviewed. One of the articles evaluated two interventions, so eight interventions were evaluated in total. Quality of the included studies was generally high, with the cross-sectional study rated as having good quality under Newcastle-Ottawa Scale, while four and two RCTs were rated as having low and some risk of bias under Cochrane risk-of-bias tool, respectively. Six of the intervention programmes were considered effective. An intervention was considered effective if it is associated with a significant (p≤0.05) and non-trivial (Cohen's d≥0.2) improvement in compliance-related outcomes such as in terms of the Morisky 8-item Medication Adherence Scale. Medication education, disease education, health education, constant reminders and medications dispensed using blister packs were identified to be effective in improving patients' compliance to medications. The importance of the continuity of interventions was also established. It is recommended that health service institutions should provide continuous education programmes, daily reminders and regular follow-ups for their patients who have CHD. It is recommended that further research ought to be carried out by using only one intervention in each trial with a standardised outcome measure, or using factorial designs, so that further cost-effectiveness evaluation of each intervention can be carried out independently, leading to the formulation of a comprehensive, optimised intervention programme for patients with CHD taking antihypertensives., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: During the COVID-19 pandemic, many primary care practices adopted telehealth in place of in-person care to preserve access to care for patients with acute and chronic conditions. The extent to which this change was associated with their rates of acute care visits (ie, emergency department visits and hospitalizations) for these conditions is unknown., Objective: To examine whether a primary care practice's level of telehealth use is associated with a change in their rate of acute care visits for ambulatory care-sensitive conditions (ACSC visits)., Design, Setting, and Participants: This retrospective cohort analysis used a difference-in-differences study design to analyze insurance claims data from 4038 Michigan primary care practices from January 1, 2019, to September 30, 2020., Exposures: Low, medium, or high tertile of practice-level telehealth use based on the rate of telehealth visits from March 1 to August 31, 2020, compared with prepandemic visit volumes., Main Outcomes and Measures: Risk-adjusted ACSC visit rates before (June to September 2019) and after (June to September 2020) the start of the COVID-19 pandemic, reported as an annualized average marginal effect. The study examined overall, acute, and chronic ACSC visits separately and controlled for practice size, in-person visit volume, zip code-level attributes, and patient characteristics., Results: A total of nearly 1.5 million beneficiaries (53% female; mean [SD] age, 40 [22] years) were attributed to 4038 primary care practices. Compared with 2019 visit volumes, median telehealth use was 0.4% for the low telehealth tertile, 14.7% for the medium telehealth tertile, and 39.0% for the high telehealth tertile. The number of ACSC visits decreased in all tertiles, with adjusted rates changing from 24.3 to 14.9 per 1000 patients per year (low), 23.9 to 15.3 per 1000 patients per year (medium), and 27.5 to 20.2 per 1000 patients per year (high). In difference-in-differences analysis, high telehealth use was associated with a higher ACSC visit rate (2.10 more visits per 1000 patients per year; 95% CI, 0.22-3.97) compared with low telehealth practices; practices in the middle tertile did not differ significantly from the low tertile. No difference was found in ACSC visits across tertiles when acute and chronic ACSC visits were examined separately., Conclusions and Relevance: In this cohort study that used a difference-in-differences analysis, the association between practice-level telehealth use and ACSC visits was mixed. High telehealth use was associated with a slightly higher overall ACSC visit rate than low telehealth practices. The association of telehealth with downstream care use should be closely monitored going forward.

Cognitive flexibility enables effective switching between mental processes to generate appropriate responses. Cholinergic neurons (CNs) within the pedunculopontine nucleus (PPN) are associated with many functions, but their contribution to cognitive flexibility remains poorly understood. Here we measure PPN cholinergic activities using calcium indicators during the attentional set-shifting task. We find that PPN CNs exhibit increasing activities correlated with rewards during each stage and error trials in reversal stages, indicating sensitivity to rule switching. Inhibition of PPN cholinergic activity selectively impairs reversal learning, which improves with PPN CN activation. Activation of PPN CNs projecting to the substantia nigra pars compacta, mediodorsal thalamus, and parafascicular nucleus in a time-locked manner with reward improves reversal learning. Therefore, PPN CNs may encode not only reward signals but also the information of changing reward contingency that contributes to guiding reversal learning through output projections to multiple nuclei that participate in flexibility., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Shipyard welders are often exposed to welding metal fumes. Ocular surfaces are continually exposed to environmental hazards. However, limited information on the associations between metal exposure and dry eye metrics in occupational settings is available. This study employed a cross-sectional design that involved the participation of 59 welders and 25 administrative staff in a shipyard in northern Taiwan from September 2020 to October 2020. The participants' individual information, laboratory data, exposure to particulate matter < 2.5 μm, urinary, and toenail metal concentrations were collected. Dry eye metrics were evaluated using standardized questionnaires and a noninvasive ocular surface analyzer. Urinary V and Cr and toenail V, Cr, Mn, Fe, Ni, Zn, As, and Cd and Pb were significantly higher in the exposed group than in the control group. After adjustment for confounding factors, dry eye metrics were associated with urinary Cd (β = 0.407; p = 0.007) and toenail Pb (β = 0.482; p = 0.002). The participants with higher urinary Cd exhibited higher odds ratios for elevated dry eye metrics. Our study revealed that exposure to welding procedures increases several metal biomarkers. In addition, urinary Cd, and toenail Pb might be related to dry eye disease in shipyard welders.

Lymphomas of the central nervous system (CNS) are broadly classified into primary CNS lymphoma (PCNSL) and secondary CNS lymphoma (SCNSL). PCNSL refers to lymphoma restricted to the brain, leptomeninges, spinal cord, or eyes without evidence of it outside the CNS at primary diagnosis, while SCNSL refers to secondary CNS involvement by systemic lymphoma. The brain is the most common site of involvement and intracranial CNS lymphoma has a highly variable imaging appearance and varies according to the patient's clinical profile and immunity. This pictorial essay aims to illustrate the different facets of intracranial CNS lymphomas on neuroimaging. This enables radiologists to be familiarized with their key diagnostic features and differentiate from their differential diagnoses, leading to early diagnosis, and treatment., Competing Interests: There are no conflicts of interest., (© 2022 Published by Scientific Scholar on behalf of Journal of Clinical Imaging Science.)

Objectives: To summarize the evidence on prevention of early childhood caries (ECC) by professionally or self-applied topical fluorides using network meta-analysis., Data: Randomized-controlled trials with minimum 1-year follow-up assessing caries-preventive effect among children younger than six years., Sources: Eight electronic databases and grey literature., Study Selection: After screening and data extraction, risk of bias assessment using Cochrane risk of bias tool 2.0 was done. Twenty-four trials were included, among which 17 were assessed as "high risk" and remaining as "low risk". Fifteen studies evaluated professionally-applied, and the other nine used self-applied topical fluorides. Ten studies on professionally-applied fluorides reporting the net caries increment (dmfs increment) at 2-years follow-up were included in Network meta-analysis (NMA). NMA and ranking the interventions were conducted using a frequentist random-effects approach and surface under the cumulative ranking command, followed by assessing the certainty of evidence using an extension of GRADE approach with CINeMA framework. Among the eight included interventions of professionally-applied fluorides, only two, i.e., 3-monthly 0.9% difluorosilane (DFS) and 6-monthly 5% sodium fluoride varnish were effective in preventing ECC compared to control with 3-monthly DFS application ranking higher than 6-monthly sodium fluoride varnish application., Conclusion: Among all the professionally-applied topical fluoride interventions reviewed, very low to moderate evidence was found with 0.9% DFS application at 3-monthly intervals, which was ranked highest in prevention of ECC. Among the included studies on self-applied topical fluorides, the evidence was inconclusive due to heterogeneity among studies., Clinical Significance: The 0.9% DFS varnish applied every 3 months is most effective for preventing early childhood caries. The review recommends that good quality studies be conducted in future, comparing two or more interventions for both self- as well as professionally-applied topical fluoride agents with adequate follow-up., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Alzheimer's disease (AD) is the most common type of dementia. Aging is a risk factor for both AD and seizures. Subclinical epileptiform discharge (SED) has no evident clinical manifestation in patients with AD. Therefore, SED is liable to be overlooked in these patients since electroencephalography is not routinely performed in clinical settings. Previous studies about the association between SED and AD have yielded inconsistent results., Objective: The current study aimed to evaluate the prevalence of SED and its effect on AD severity and clinical outcomes., Methods: Patients with AD from Kaohsiung Municipal Ta-tung Hospital were included in this study. International 10-20 system scalp electroencephalography for 13 minutes was performed to detect SED. Clinical outcomes of patients with and without SED were assessed by neuropsychological tests [Cognitive Abilities Screening Instrument (CASI), Mini-Mental State Examination (MMSE), and Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB)]., Results: 288 patients (mean age 80.5 years, 60.4% female) were enrolled in this study. Fifty-seven (19.8%) out of 288 patients with AD had SED. The prevalence of SED increased with the severity of cognitive impairment. Compared with patients without SED, those with SED showed significantly greater decline in CASI (-9.32 versus -3.52 points, p = 0.0001) and MMSE (-2.52 versus -1.12 points, p = 0.0042) scores in one year., Conclusion: SED may play a significant role in AD progression and is a potential therapeutic target.

Background: An angiomyolipoma usually occurs in the kidneys and rarely in the liver. Hepatic epithelioid angiomyolipoma (HEAML), a rare variant of angiomyolipoma, possesses malignant potential and mimics the imaging features of hepatocellular carcinoma. Sonazoid® (perfluorobutane microbubbles), a new contrast agent that facilitates hepatic parenchyma-specific Kupffer phase imaging on contrast-enhanced ultrasonography (CEUS), is useful for the detection and characterization of focal liver lesions., Case Presentation: A 30-year-old man with HEAML underwent CEUS using Sonazoid®, in which new concepts for ultrasonography-based differentiation between HEAML and hepatocellular carcinoma were applied., Conclusions: This case report provides clinicians and radiologists with a reference for distinguishing HEAML from hepatocellular carcinoma based on CEUS using Sonazoid®., (© 2021. The Author(s).)

Introduction: Previous studies have shown that whole-body vibration (WBV) may have a potential impact on gait and balance in individuals with Parkinson's disease (PD). However, this body of work has proven inconclusive due to the diverse disease progression and broad age range associated with PD. The effects of WBV on proprioception, a sense frequently affected by PD, has rarely been studied., Objective: To investigate the short-term effect of WBV on proprioception and motor function for individual with moderate PD., Design: A single-blind randomized controlled trial. Setting. A hospital and a laboratory. Participants. 32 participants with moderate PD were recruited and randomly assigned into either the WBV or conventional therapy groups. Interventions. For the WBV group, each treatment session included five, one-minute bouts of whole-body vibration paired with one-minute rest (frequency: 6 Hz; amplitude: 3 mm). Each conventional therapy participant received balance and mobility training for 10 minutes. Main Outcome Measures. Outcome measures included proprioceptive sensitivity of the upper limb, position sense of the knee joint, Unified Parkinson's disease rating scale : motor section (UPDRS-motor), functional reach test (FRT), and the timed up and go test (TUG)., Results: No statistically significant difference was found between groups. However, both groups showed a significant improvement in motor function after treatment, including UPDRS-motor ( P = 0.04), less affected side of FRT ( P = 0.019), and TUG ( P = 0.006)., Conclusions: Although the effect of WBV was not superior to the conventional therapy, it provided a passive and safe clinical intervention as an alternative treatment, especially for individuals with motor impairment or poor balance function., Competing Interests: The authors have no conflict of interest to declare., (Copyright © 2021 Kuan-yi Li et al.)

Prolonged cold ischemia (CI) is a risk factor for acute kidney injury (AKI) after kidney transplantation (KT). AKI is an abrupt and rapid reduction in renal function due to multi-factors, including inflammation, oxidative stress and apoptosis. V-set immunoglobulin-domain-containing 4 (VSIG4) is a B7 family-related protein and specifically expressed in resting tissue-resident macrophages to mediate various cellular events. In the study, we attempted to explore the effects of VSIG4 on CI/KT-induced AKI in a mouse model. Our results showed that VSIG4 expression was markedly down-regulated in serum of kidney transplant recipients with acute rejection, and in renal tissues of cold ischemia-reperfusion (IR)-operated mice with AKI, which was confirmed in murine macrophages stimulated by oxygen glucose deprivation/reoxygenation (OGD/R). We then found that exogenous VSIG4 markedly ameliorated histological changes in kidney of CI/KT mice by suppressing inflammation and apoptosis through restraining nuclear factor-κB (NF-κB) and Caspase-3 activation, respectively. Oxidative stress and reactive oxygen species (ROS) accumulation in renal tissues were also mitigated by exogenous VSIG4 in CI/KT mice through improving nuclear factor-erythroid 2 related factor 2 (Nrf2) nuclear expression. The inhibitory effects of VSIG4 on inflammation, ROS generation and cell death were confirmed in OGD/R-treated macrophages, which further ameliorated oxidative damage and apoptosis in podocytes. More in vivo and in vitro studies showed that CI/KT- and OGD/R-induced AKI was further accelerated by VSIG4 knockdown. Mechanistically, VSIG4 directly interacted with AKT, and AKT activation was necessary for VSIG4 to govern all these above mentioned cellular processes. Collectively, our findings demonstrated that VSIG4 could mitigate AKI in a CI/KT mouse model, and we identified VSIG4/AKT axis as a promising therapeutic target for the treatment of the disease., (Copyright © 2021. Published by Elsevier Inc.)

BCAT2-mediated branched-chain amino acid (BCAA) catabolism is critical for pancreatic ductal adenocarcinoma (PDAC) development, especially at an early stage. However, whether a high-BCAA diet promotes PDAC development in vivo , and the underlying mechanism of BCAT2 upregulation, remain undefined. Here, we find that a high-BCAA diet promotes pancreatic intraepithelial neoplasia (PanIN) progression in LSL-Kras G12D/+ ; Pdx1-Cre (KC) mice. Moreover, we screened with an available deubiquitylase library which contains 31 members of USP family and identified that USP1 deubiquitylates BCAT2 at the K229 site. Furthermore, BCAA increases USP1 protein at the translational level via the GCN2-eIF2α pathway both in vitro and in vivo . More importantly, USP1 inhibition recedes cell proliferation and clone formation in PDAC cells and attenuates pancreas tumor growth in an orthotopic transplanted mice model. Consistently, a positive correlation between USP1 and BCAT2 is found in KC; LSL-Kras G12D/+ ; p53 flox/+ ; Pdx1-Cre mice and clinical samples. Thus, a therapeutic targeting USP1-BCAT2-BCAA metabolic axis could be considered as a rational strategy for treatment of PDAC and precisive dietary intervention of BCAA has potentially translational significance., (© The Author(s) 2021. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

Mastitis in dairy cow significantly affects animal performance, ultimately reducing profitability. The reciprocal interrelationships among ruminal microbiota, metabolome, and mastitis combining early inflammatory factors (serum proinflammatory cytokines) in lactating dairy cows has not been explored, thus, this study evaluated these reciprocal interrelationships in early lactating Holstein dairy cows to identify potential microbial biomarkers and their relationship with ruminal metabolites. The ruminal fluid was sampled from 8 healthy and 8 mastitis cows for the microbiota and metabolite analyses. The critical ruminal microbial biomarkers and metabolites related to somatic cell counts (SCC) and serum proinflammatory cytokines were identified by the linear discriminant analysis effect size (LEfSe) algorithm and Spearman's correlation analysis, respectively. The SCC level and proinflammatory cytokines positively correlated with Sharpea and negatively correlated with Ruminococcaceae UCG-014 , Ruminococcus flavefaciens , and Treponema saccharophilum . Furthermore, the metabolites xanthurenic acid, and 1-(1H-benzo[d]imidazol-2-yl) ethan-1-ol positively correlated with microbial biomarkers of healthy cows, whereas, xanthine, pantothenic acid, and anacardic acid were negatively correlated with the microbial biomarkers of mastitis cows. In conclusion, Ruminococcus flavefaciens and Treponema saccharophilum are potential strains for improving the health of dairy cows. The current study provides a novel perspective to assist in targeting the ruminal microbiota with preventive/therapeutic strategies against inflammatory diseases in the future.

Objective: To investigate relationship of tumor stage-based gross tumor volume (GTV) of esophageal squamous cell carcinoma (ESCC) measured on computed tomography (CT) with early recurrence (ER) after esophagectomy., Materials and Methods: Two hundred and four consecutive patients with resectable ESCC including 159 patients enrolled in the training cohort (TC) and 45 patients in validation cohort (VC) underwent contrast-enhanced CT less than 2 weeks before esophagectomy. GTV was retrospectively measured by multiplying sums of all tumor areas by section thickness. For the TC, univariate and multivariate analyses were performed to determine factors associated with ER. Mann-Whitney U test was conducted to compare GTV in patients with and without ER. Receiver operating characteristic (ROC) analysis was performed to determine if tumor stage-based GTV could predict ER. For the VC, unweighted Cohen's Kappa tests were used to evaluate the performances of the previous ROC predictive models., Results: ER occurred in 63 of 159 patients (39.6%) in the TC. According to the univariate analysis, histologic differentiation, cT stage, cN stage, and GTV were associated with ER after esophagectomy (all P -values < 0.05). Multivariate analysis revealed that cT stage and GTV were independent risk factors with hazard ratios of 3.382 [95% confidence interval (CI): 1.533-7.459] and 1.222 (95% CI: 1.125-1.327), respectively (all P -values < 0.05). Mann-Whitney U tests showed that GTV could help differentiate between ESCC with and without ER in stages cT 1-4a , cT 2 , and cT 3 (all P -values < 0.001), and the ROC analysis demonstrated the corresponding cutoffs of 13.31, 17.22, and 17.83 cm 3 with areas under the curve of more than 0.8, respectively. In the VC, the Kappa tests validated that the ROC predictive models had good performances for differentiating between ESCC with and without ER in stages cT 1-4a , cT 2 , and cT 3 with Cohen k of 0.696 (95% CI, 0.498-0.894), 0.733 (95% CI, 0.386-1.080), and 0.862 (95% CI, 0.603-1.121), respectively., Conclusion: GTV and cT stage can be independent risk factors of ER in ESCC after esophagectomy, and tumor stage-based GTV measured on CT can help predict ER., 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 Wu, Tang, Tan, Yang, Lu, Chen, Ou, Zhang, Gao, Li, Yu and Tang.)

The present study observed the effect of Guanxin Zhitong Capsules(GXZT) on the lipotoxicity of vascular endothelial cells and investigated the mechanism of GXZT in atherosclerosis treatment. The lipotoxicity model in human umbilical vein endothelial cells(HUVECs) was induced by palmitic acid(PA) stimulation. These cells were divided into a normal control group(NC, 15% normal serum), a model group(PA, 0.6 mmol·L~(-1) PA+15% normal serum), a high-dose GXZT group(GXZT-H, 0.6 mmol·L~(-1) PA+15% GXZT-medicated serum), a medium-dose GXZT group(GXZT-M, 0.6 mmol·L~(-1) PA+10% GXZT-medicated serum+5% normal serum) and a low-dose GXZT group(GXZT-L, 0.6 mmol·L~(-1) PA+5% GXZT-medicated serum+10% normal serum). HUVECs were detected for cell viability by cell counting kit-8(CCK-8) assay, apoptosis by flow cytometry, mitochondrial membrane potential(MMP) by JC-1 labeled laser scanning confocal microscopy, and total and phosphorylated proteins of p38, ERK1/2, and JNK1/2 in the mitogen-activated protein kinases(MAPK) signaling pathway by Western blot. The phosphorylated level was calcula-ted. Compared with the NC group, the PA group showed decreased cell viability and MMP(P&lt;0.01, P&lt;0.01), elevated apoptosis(P&lt;0.01), and up-regulated phosphorylated levels of p38, ERK1/2, and JNK1/2(P&lt;0.01, P&lt;0.01, P&lt;0.01). Compared with the PA group, the GXZT-H, GXZT-M, and GXZT-L groups showed increased cell viability and MMP(P&lt;0.01, P&lt;0.01, P&lt;0.01), reduced apoptosis(P&lt;0.01), and down-regulated protein expression and phosphorylated levels of p38, ERK1/2 and JNK1/2 in the MAPK signaling pathway(P&lt;0.01, P&lt;0.01, P&lt;0.01). In conclusion, the results suggest that GXZT functions via blocking MAPK signaling pathway to relieve the damage of HUVECs induced by PA.

Transcription initiation by RNA polymerase II (RNA Pol II) requires preinitiation complex (PIC) assembly at gene promoters. In the dynamic nucleus, where thousands of promoters are broadly distributed in chromatin, it is unclear how multiple individual components converge on any target to establish the PIC. Here we use live-cell, single-molecule tracking in S. cerevisiae to visualize constrained exploration of the nucleoplasm by PIC components and Mediator's key role in guiding this process. On chromatin, TFIID/TATA-binding protein (TBP), Mediator, and RNA Pol II instruct assembly of a short-lived PIC, which occurs infrequently but efficiently within a few seconds on average. Moreover, PIC exclusion by nucleosome encroachment underscores regulated promoter accessibility by chromatin remodeling. Thus, coordinated nuclear exploration and recruitment to accessible targets underlies dynamic PIC establishment in yeast. Our study provides a global spatiotemporal model for transcription initiation in live cells., Competing Interests: Declaration of interests T.L. holds intellectual property rights related to Janelia Fluor dyes used in this publication. L.D.L. and Q.Z. are listed as inventors on patents and patent applications whose values might be affected by publication., (Published by Elsevier Inc.)

Selective photocatalysis is a very promising direction to improve the activities of photocatalysts. Combining the technique of molecular imprinting (MIP) with heterogeneous photocatalysis can be an appealing approach to achieve our aim. Herein, using the MIP technique, the monoclinic MIP-BiVO₄ was successfully synthesized by the presence of rhodamine B (RhB) during the hydrothermal synthesis. The synthesized MIP-BiVO₄ possessed better adsorptive and photocatalytic activities than pristine BiVO₄. RhB added in the synthesis process worked as a template and served a crucial role in the formation of the MIP-BiVO₄ morphology. The photoelectrochemical analysis verified the superiority of MIP-BiVO₄ sample in the transfer and separation of the electron-hole pairs. Holes played the most crucial role in the degradation of the pollutants. The effective approach combining MIP technique in the synthesis of photocatalysts would provide some guidance to selective photocatalysis field for designing and synthesizing highly efficient photocatalysts.

Objectives: Purpose of the present study was to evaluate the effect of surface roughness on the time-dependent wear performance of lithium disilicate (LD) glass-ceramic., Methods: Friction pairs (pin and disk specimens) were prepared by IPS e.max® Press lithium disilicate glass-ceramic. The lateral faces of friction pairs (N = 12) were grinded with silicon carbide papers, and 6 friction pairs were polished with a 0.25 μm diamond suspension after grinding. The friction pairs were tested for wear performance using a pin-on-disk tribometer with 10 N for 1.02 × 10 6 wear cycles in artificial saliva. Wear analysis of the pin and disk was performed with a 3D profilometer. The microstructure and worn surface morphology were examined with scanning electron microscopy. One-way analysis of variance and Tukey's post-hoc pairwise comparison were used to analyze the wear data., Results: The two group LD friction pairs presented strong time-dependent wear performance. The polished group (GP) exhibited a high wear rate and extensive surface wear during 0-1 × 10 5 cycles (running-in wear stage). The wear rate, height loss and surface roughness were obviously lower than those of grinded group (GG) in running-in wear stage. However, these wear parameters were similar during the steady wear stage. The worn surface topographies of the pin and disk in GP were smoother at the same cycle before the GG entering the steady wear stage., Conclusion: Running-in, which means the initial stage of wear process, is a critical period to determine the final wear loss and surface degradation, when compare the wear behavior of lithium disilicate ceramic with different initial surface states. Ceramic layer with smooth contact area leads to low wear rate and short running-in wear stage., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: Our purpose was to investigate whether people with a previous human papillomavirus (HPV) infection were associated with an increased risk of Bell's palsy (BP). Methods: By using Taiwan population-based data, patients aged > 18 years with HPV infection ( n = 22,260) from 2000 to 2012 were enrolled and compared with control subjects who had never been diagnosed with an HPV infection at a 1:4 ratio matched by sex, age, index date, and co-morbidities ( n = 89,040). The index date was the first date of HPV diagnosis. All the patients were tracked until the occurrence of BP. Cox proportional hazards regression was applied to estimate the hazard ratios (HRs) for the development of BP in both groups. Results: The HPV group had 1.25 [95% confidence interval (CI) = 1.03-1.51] times higher risk of BP compared with the non-HPV group after adjusting for sex, age, and co-morbidities. The association of HPV and BP was significant in the sensitivity analyses. In the subgroup analysis, the impact of HPV infection on the risk of BP was more pronounced in the elderly > 50 years [adjusted hazard ratio (aHR) =1.86; 95% CI = 1.37-2.52], hypertension (aHR = 1.65; 95% CI = 1.17-2.31), and chronic obstructive pulmonary disease (aHR = 2.14, 95% CI 1.333.43) subgroups. Conclusions: Patients with HPV infection have a higher risk of subsequent BP compared with non-HPV patients. More rigorous studies are needed to confirm if and how specific HPV genotypes are associated with BP and the possible role of vaccines in disease prevention., 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 Li, Chou, Chang, Yip, Hung and Wei.)

Objective: To investigate the epidemiological relationship between dengue fever and the subsequent development of dementia., Methods: Using nationwide Taiwan registries from the National Health Insurance Research (NHIRD), we identified adults aged over 40 years who received a dengue fever diagnosis from 1 January 2000 to 31 December 2012 and who did not have a history of dementia. We used a propensity score match (PSM) to balance the baseline characteristics between groups. All eligible adults were sorted into either the dengue group or non-dengue group at a ratio of 1:4, matching by age, sex, index years, income level, and relevant comorbidities. Using Cox regression with proportional hazards models, we estimated the risk of dementia. The study period started from 1 January 2000 to 31 December 2013. We conducted sensitivity analyses to cross-validate study results., Results: With a median of 8.01 years of follow-up, patients in the dengue group were more at risk of developing dementia than the non-dengue group. The estimated cumulative incidence of dementia was 7.21% in the dengue group and 4.03% in the non-dengue group (adjusted hazard ratio (aHR), 1.71; 95% CI, 1.03 to 2.83). Sensitivity analyses yielded consistent findings. We excluded any stroke cases before the end of the study, and subgroup analysis by follow-up time showed that the dengue group has a significantly higher risk of new-onset dementia >6 years after the index date (aHR 3.24; 95% CI, 1.42 to 7.37). The P value for interaction was significant (<.0001)., Conclusions: This study demonstrated a significantly higher risk of dementia in patients with dengue fever in Taiwan than in those without dengue fever., (© 2021 John Wiley & Sons Ltd.)

Conserved ATP-dependent chromatin remodelers establish and maintain genome-wide chromatin architectures of regulatory DNA during cellular lifespan, but the temporal interactions between remodelers and chromatin targets have been obscure. We performed live-cell single-molecule tracking for RSC, SWI/SNF, CHD1, ISW1, ISW2, and INO80 remodeling complexes in budding yeast and detected hyperkinetic behaviors for chromatin-bound molecules that frequently transition to the free state for all complexes. Chromatin-bound remodelers display notably higher diffusion than nucleosomal histones, and strikingly fast dissociation kinetics with 4-7 s mean residence times. These enhanced dynamics require ATP binding or hydrolysis by the catalytic ATPase, uncovering an additional function to its established role in nucleosome remodeling. Kinetic simulations show that multiple remodelers can repeatedly occupy the same promoter region on a timescale of minutes, implicating an unending 'tug-of-war' that controls a temporally shifting window of accessibility for the transcription initiation machinery., Competing Interests: JK, PV, VJ, SL, XT, KL, JS, CW No competing interests declared, QZ, LL LDL and QZ are listed as inventors on patents and patent applications whose value might be affected by publication. US Patent 9,933,417 and Patent Application 2021/0085805 describing azetidine-containing fluorophores and variant compositions (with inventors QZ, LDL, and TL) are assigned to HHMI. TL TL holds intellectual property rights related to Janelia Fluor dyes used in this publication. US Patent 9,933,417 and Patent Application 2021/0085805 describing azetidine-containing fluorophores and variant compositions (with inventors QZ, LDL, and TL) are assigned to HHMI., (© 2021, Kim et al.)

Importance: While telehealth use in surgery has shown to be feasible, telehealth became a major modality of health care delivery during the COVID-19 pandemic., Objective: To assess patterns of telehealth use across surgical specialties before and during the COVID-19 pandemic., Design, Setting, and Participants: Insurance claims from a Michigan statewide commercial payer for new patient visits with a surgeon from 1 of 9 surgical specialties during one of the following periods: prior to the COVID-19 pandemic (period 1: January 5 to March 7, 2020), early pandemic (period 2: March 8 to June 6, 2020), and late pandemic (period 3: June 7 to September 5, 2020)., Exposures: Telehealth implementation owing to the COVID-19 pandemic in March 2020., Main Outcomes and Measures: (1) Conversion rate defined as the rate of weekly new patient telehealth visits divided by mean weekly number of total new patient visits in 2019. This outcome adjusts for a substantial decrease in outpatient care during the pandemic. (2) Weekly number of new patient telehealth visits divided by weekly number of total new patient visits., Results: Among 4405 surgeons in the cohort, 2588 (58.8%) performed telehealth in any patient care context. Specifically for new patient visits, 1182 surgeons (26.8%) used telehealth. A total of 109 610 surgical new outpatient visits were identified during the pandemic. The median (interquartile range) age of telehealth patients was 46.8 (34.1-58.4) years compared with 52.6 (38.3-62.3) years for patients who received care in-person. Prior to March 2020, less than 1% (8 of 173 939) of new patient visits were conducted through telehealth. Telehealth use peaked in April 2020 (week 14) and facilitated 34.6% (479 of 1383) of all new patient visits during that week. The telehealth conversion rate peaked in April 2020 (week 15) and was equal to 8.2% of the 2019 mean weekly new patient visit volume. During period 2, a mean (SD) of 16.6% (12.0%) of all new patient surgical visits were conducted via telehealth (conversion rate of 5.1% of 2019 mean weekly new patient visit volumes). During period 3, 3.0% (2168 of 71 819) of all new patient surgical visits were conducted via telehealth (conversion rate of 2.5% of 2019 new patient visit volumes). Mean (SD) telehealth conversion rates varied by specialty with urology being the highest (14.3% [7.7%])., Conclusions and Relevance: Results from this study showed that telehealth use grew across all surgical specialties in Michigan in response to the COVID-19 pandemic. While rates of telehealth use have declined as in-person care has resumed, telehealth use remains substantially higher across all surgical specialties than it was prior to the pandemic.

We demonstrated a deep-red laser source by intracavity frequency-doubled crystalline Raman laser for the first time, to the best of our knowledge. The actively Q -switched 1314 nm N d : L i Y F 4 laser was first converted to the eye-safe Raman laser using a K G d ( W O 4 ) 2 (KGW) crystal, which was subsequently frequency-doubled in a bismuth borate crystal. Benefiting from the KGW bi-axial properties, the deep-red laser source was able to lase separately at two different spectral lines at 730 and 745 nm. Under an optimal repetition rate of 4 kHz, the maximum average powers of 1.7 and 2.0 W were attained with good beam quality of M 2 ≈1.7. The corresponding pulse durations were determined to be 3.0 and 2.8 ns with the peak powers up to approximately 140 and 180 kW, respectively.

Background: Pouchitis is a common complication after ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis. However, an ideal model remains lacking. Therefore, we aimed to establish an appropriate model resembling human pouchitis., Methods: Sprague-Dawley rats were randomly assigned to five groups: TNBS group, DSS group, NS group (following IPAA procedure, administrated with TNBS enema, DSS orally, normal saline enema, respectively), NI group (underwent IPAA), and sham group (underwent switch abdominal surgery). General status, weight change, hematochezia, and fecal scores were recorded. Fecal microbiota were counted under a microscope and analyzed by 16S rRNA gene high-throughput sequencing. Specimens of ileal pouch and small intestine (proximal, mid, distal) were collected to evaluate myeloperoxidase and occludin expression by immunohistochemistry and mRNA expression of pro-inflammatory markers by PCR., Results: General status, hematochezia, fecal score, and increased mRNA expression of interleukin-6 and TNF-α in the TNBS group were similar to those in the DSS group, whereas the TNBS-induced model displayed a more stable weight change and more serious dysbacteriosis, not only was fecal bacterial diversity reduced, the dominant microbiota was altered. Histopathology scores of the distal small intestine in the TNBS group were lower compared with those in the DSS group (P < 0.05). A significant difference in myeloperoxidase and occludin expression in the small intestine was also detected between the TNBS and DSS groups., Conclusions: Our model mimicked the characteristics of human pouchitis and avoided potential side effects in the small intestine, and thus could be employed for further research.

Emergency department (ED) crowding is recognized as a critical threat to patient safety, while sub-optimal ED patient flow also contributes to reduced patient satisfaction and efficiency of care. Provider in triage (PIT) programs-which typically involve, at a minimum, a physician or advanced practice provider conducting an initial screening exam and potentially initiating treatment and diagnostic testing at the time of triage-are frequently endorsed as a mechanism to reduce ED length of stay (LOS) and therefore mitigate crowding, improve patient satisfaction, and improve ED operational and financial performance. However, the peer-reviewed evidence regarding the impact of PIT programs on measures including ED LOS, wait times, and costs (as variously defined) is mixed. Mechanistically, PIT programs exert their effects by initiating diagnostic work-ups earlier and, sometimes, by equipping triage providers to directly disposition patients. However, depending on local contextual factors-including the co-existence of other front-end interventions and delays in ED throughput not addressed by PIT-we demonstrate how these features may or may not ultimately translate into reduced ED LOS in different settings. Consequently, site-specific analysis of the root causes of excessive ED LOS, along with mechanistic assessment of potential countermeasures, is essential for appropriate deployment and successful design of PIT programs at individual EDs. Additional motivations for implementing PIT programs may include their potential to enhance patient safety, patient satisfaction, and team dynamics. In this conceptual article, we address a gap in the literature by demonstrating the mechanisms underlying PIT program results and providing a framework for ED decision-makers to assess the local rationale for, operational feasibility of, and financial impact of PIT programs., Competing Interests: The authors declare no conflicts of interest., (© 2021 The Authors. JACEP Open published by Wiley Periodicals LLC on behalf of American College of Emergency Physicians.)

Pogostemon cablin has been indicated to treat many kinds of diseases and the progression of cancers, such as colorectal cancer. However, the effects of P. cablin extract (PPa extract) against acute myeloid leukemia have not been investigated. Thus, this study explored the anticancer potential of PPa extract and its mechanism in HL-60 cells. The MTT assay results showed that PPa extract significantly inhibited the proliferation of HL-60 cells in a dose-dependent manner and affected cell morphology, causing cell shrinkage and the formation of debris. PPa extract blocked cell cycle progression at the G 0 /G 1 phase in a dose- and time-dependent manner and induced cell apoptosis, as shown by the observation of DNA fragments and apoptotic bodies. Furthermore, PPa extract caused the accumulation of a population of cells at G 0 /G 1 phase via a reduction in p-Rb, increasing p21 expression, and downregulating cell cycle regulator protein expression. Then, PPa extract was found to activate the extrinsic and intrinsic apoptosis pathways, leading to cell death. These data demonstrated that PPa extract exerted inhibitory activity and triggered cell apoptosis in HL-60 cells and that PPa extract might be a chemopreventive agent for cancer therapy., Competing Interests: The authors declare that they have no conflict of interest., (© 2021 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Background: Oral antiseizure medications (ASMs) are first-line treatments for patients with epilepsy. However, ASMs may alter sleep architecture, adversely affecting patient outcomes. The meta-analysis aimed to elucidate the effect of ASMs on sleep architecture., Methods: PubMed, Embase, and Cochrane Central database (up to Febrary 2021) were searched for randomized control trials (RCT) with effects of ASMs on polysomnography parameters. A meta-analysis using a random-effects model was performed. We did not set limitation to the participants with underlying diagnosis of epilepsy., Results: Eighteen randomized-controlled trials fulfilled the eligibility criteria. The effects of five main groups of ASMs (sodium channel blockers, calcium channel blockers, GABA enhancers, synaptic vesicle glycoprotein 2A [SV2A] ligand, and broad-spetrum ASMs) on slow-wave sleep (SWS), rapid eye movement (REM) sleep, and sleep efficiency (SE) were analyzed. Compared with placebo, calcium channel blockers and GABA enhancers significantly increased SWS. GABA enhancers also decreased REM sleep percentage, whereas calcium channel blockers significantly increased SE. Sodium channel blockers, SV2A ligand and broad-spectrum ASMs did not affect SWS, REM sleep, or SE. The subgroup analysis revealed that gabapentin, pregabalin, and tiagabine increased the percentage of SWS. Tiagabine also decreased REM sleep, whereas pregabalin increased SE. Finally, levetiracetam did not affect SWS, REM sleep, and SE., Conclusions: This meta-analysis indicated that ASMs can have a statistically significant effect on sleep parameters; the effect differs between ASMs., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Thioredoxin-2 (TXN2) is a mitochondrial protein and represents one of the intrinsic antioxidant enzymes. It has long been recognized that mitochondrial dysfunction and oxidative stress contribute to the pathogenesis of Alzheimer's disease (AD). We hypothesized that mitochondrial TXN2 might play a role in AD-like pathology. In this study, we found that in SH-SY5Y and HEK cells stably express full-length human amyloid-β precursor protein (HEK-APP), TXN2 silencing or over-expression selectively increased or decreased the transcription of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), respectively, without altering the protein levels of others enzymes involved in the catalytic processing of APP. As a result, β-amyloid protein (Aβ) levels were significantly decreased by TXN2. In addition, in cells treated with 3-nitropropionic acid (3-NP) that is known to increase reactive oxygen species (ROS) and promote mitochondrial dysfunction, TXN2 silencing resulted in further enhancement of BACE1 protein levels, suggesting a role of TXN2 in ROS removal. The downstream signaling might involve NFκB, as TXN2 reduced the phosphorylation of p65 and IκBα; and p65 knockdown significantly attenuated TXN2-mediated regulation of BACE1. Concomitantly, the levels of cellular ROS, apoptosis-related proteins and cell viability were altered by TXN2 silencing or over-expression. In APPswe/PS1E9 mice, an animal model of AD, the cortical and hippocampal TXN2 protein levels were decreased at 12 months but not at 6 months, suggesting an age-dependent decline. Collectively, TXN2 regulated BACE1 expression and amyloidogenesis via cellular ROS and NFκB signaling. TXN2 might serve as a potential target especially for early intervention of AD., (© 2020 International Society for Neurochemistry.)

Objective: Oral and maxillofacial surgery (OMFS) is a high-risk specialty involving airway and aerosol-generating procedures, which is potentially of more risk in the era of coronavirus disease 2019 (COVID-19). We aimed to identify the impact of COVID-19 on the disease pattern of OMFS inpatients and surgeries under general anesthesia in a comparative study. Materials and Methods: We reviewed the admission and operating theater records of OMFS patients from Jan 1 to Aug 31 in 2020 and 2019. The total number of cases, presenting disease patterns, and proportion of essential and non-essential medical services were compared between 2020 and 2019. Results: There were 664 admissions and 356 general anesthesia surgical procedures included in this study. Both admission and surgery numbers were significantly reduced in 2020, compared with 2019 ( p = 0.012 and 0.007, respectively). The proportion of malignancy cases increased significantly, whereas that of cleft lip and palate and temporomandibular disorder (TMD) decreased. There was a significant increase in the proportion of essential services compared with non-essential services in 2020 compared with 2019. Conclusion: Our results first reported the epidemiological data of the impact of COVID-19 on OMFS disease pattern in a comparative study. The change of disease pattern and caseload will have a long-term impact on OMFS patient care, education, and training during the pandemic. Our paper provides evidence for health policy makers to consider the relocation of medical resources and optimization of medical education and services., 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 Pu, McGrath, Leung, Choi, Yang, Li and Su.)

A pot experiment was carried out to study the impacts of five organic materials (rape straw, broad bean stalk, peat, pig manure compost, and biochar) on the availability of arsenic (As) and cadmium (Cd) in soil, the amount of iron plaque on the root surface, as well as the uptake and translocation of As and Cd in rice grown in an As/Cd co-contaminated yellow paddy soil. The results indicated that the application of organic materials significantly increased the contents of the soil organic matter and the yield of rice. The application of broad bean stalk, peat, pig manure compost, and biochar remarkably increased the soil pH, while the application of rape straw exerted no significant influence. The addition of organic matter reduced the available Cd content by 34.77%-82.69%. However, the effects of organic materials on the availability of As varied with the organic materials. The soil-available As content was significantly increased by the application of pig manure compost and biochar, while it was significantly decreased by adding rape straw and peat. The application of organic materials increased As and Cd contents in the Fe plaques on rice root surface by 28.49%-94.86% and 17.73%-151.03%, respectively. It also reduced the As and Cd contents in brown rice by 27.04%-82.51% and 15.87%-79.45%, respectively. The largest decrease was observed in the biochar treatment. The application of organic materials also remarkably reduced the translocation efficiency of Cd from the root-stem-leaf-grain and that of As from the stem to grain. The correlation analysis revealed that the soil pH, available Cd, and Cd content in the Fe plaques are the major factors influencing the accumulation of Cd in the rice grain. Furthermore, the soil pH, soil organic matter, and As content in the Fe plaques are the major factors influencing the accumulation of As in the rice grain. Therefore, it has been concluded that organic materials could influence the uptake and translocation of As and Cd in rice through changing the soil pH, organic matter content, and As and Cd contents in the Fe plaques.

Use of direct-to-consumer telemedicine-on-demand virtual care for minor medical issues-is growing rapidly. Although it may yield immediate savings by diverting health care from higher-cost settings, these savings could be countered if direct-to-consumer telemedicine increases follow-up care and, therefore, episode costs. Comparing downstream care utilization data from a large, commercial payer for the period 2016-19, we found that patients with initial visits for acute respiratory infection were more likely to obtain follow-up care within seven days after direct-to-consumer telemedicine visits (10.3 percent) than after in-person visits (5.9 percent). In both settings approximately 90 percent of patients did not obtain additional care. The telemedicine cohort had fewer (0.5 percent versus 0.6 percent) emergency department visits-a small but statistically significant difference-but more subsequent office, urgent care, and telemedicine visits. Our findings suggest that potential savings from shifting initial care to a direct-to-consumer telemedicine setting should be balanced against the potential for higher spending on downstream care.

In this paper, the protein changes during aging and the differences in the myofibrillar protein fraction at 1 h postmortem of pale, soft and exudative (PSE), and red, firm and non-exudative (RFN) pork longissimus thoracis (LT) were comparatively studied. The PSE and RFN groups were screened out based on the differences in their pH and lightness ( L* ) at 1 h, and their purge loss at 24 h postmortem. Based on the measured MFI, desmin degradation, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis, PSE meat presented more significant changes in the myofibrillar protein fraction compared to RFN meat during postmortem aging. Through liquid chromatograph-mass spectrometer/mass spectrometer (LC-MS/MS) analysis, a total of 172 differential proteins were identified, among which 151 were up-regulated and 21 were down-regulated in the PSE group. The differential proteins were muscle contraction, motor proteins, microfilaments, microtubules, glycolysis, glycogen metabolism, energy metabolism, molecular chaperones, transport, and enzyme proteins. The AMP activated protein kinase (AMPK) signaling pathway, HIF-1 signaling pathway, calcium signaling pathway, and PI3K-Akt signaling pathway were identified as the significant pathways related to meat quality. This study suggested that the different changes of the myofibrillar protein fraction were involved in the biochemical metabolism in postmortem muscle, which may contribute to the molecular understanding of PSE meat formation.