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Hui-Feng Zhu,1,* Yali Shao,1,* Lei Qin,1,* Jing-Huan Wang,1 Shan Feng,1 Yun-Bin Jiang,1 Dong Wan2 1Department of Pharmacy, College of Pharmaceutical Sciences and Chinese Medicine, Southwest University, Chongqing 400715, People’s Republic of China; 2Department of Emergency, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hui-Feng ZhuDepartment of Pharmacy, College of Pharmaceutical Sciences and Chinese Medicine, Southwest University, Chongqing 400715, People’s Republic of ChinaEmail zhfbswu@swu.edu.cnDong WanDepartment of Emergency, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of ChinaTel +86-23-68251225Email wandongcqykdx@126.comBackground: The role of catalpol in brain neurogenesis and newborn neuron survival has not been previously determined in permanent middle cerebral artery occlusion (pMCAO).Methods: Fifty-four rats were divided into 6 groups: pMCAO (model, n=9); sham operation (NS, n=9); catalpol treatment (5 mg/kg and 10 mg/kg subgroups, n=9 each); K252a (n=9); and K252a+catalpol 5 mg/kg (n=9) with stroke. The effects of catalpol on behavior, neurogenesis surrounding the infarction ipsilateral to pMCAO, and the expression of brain-derived neurotrophic factor (BDNF) and its receptor (TrkB) were evaluated. Vehicle or, K252a (i.p.), an inhibitor of TrkB phosphorylase.Results: Repeated administration of catalpol reduced neurological deficits and significantly improved neurogenesis. Catalpol increased the number of newborn immature neurons, as determined by BrdU+-Nestin+ and BrdU+-Tuj-1+ staining, and downregulated cleaved caspase 3 in Tuj-1+ cells at day 7 following stroke. Moreover, catalpol increased the protein expression of Tuj-1, MAP2, and the Bcl-2/Bax ratio, as determined using Western blot. Catalpol also significantly increased brain levels of BDNF, but not TrkB, resulting in enhanced survival of newborn neurons via inhibition of apoptosis.Conclusion: Catalpol may contribute to neurogenesis in infarcted brain regions and help promote the survival of newborn neurons by activating BDNF, but not BDNF/TrkB signaling.Keywords: catalpol, neurogenesis, permanent middle cerebral artery occlusion, pMCAO, brain derived neurotrophic factor, BDNF, neurological function

Dan Zong, Ning Jiang, Jian-Hua Xu, De-Jun Wang, Huan-Feng Zhu, Li-Rong Wu, Cheng Chen, Li Yin, Xia HeJiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu Province 210009, People’s Republic of ChinaBackground: ZNF488 acts as an oncogene which promotes cell invasion and endows tumor cells stem cell capacity in nasopharyngeal carcinoma (NPC), but its correlation with clinicopathologic characteristics and patients’ survival in NPC remain undefined.Methods: In this study, 158 cases of confirmed NPC were subjected to immunohistochemistry staining for evaluating endogenous expression. Kaplan–Meier method and log-rank test were used to estimate the survival rates. The relationship between ZNF488 and clinicopathological characteristics was statistically calculated by chi-squared test, univariate and multivariate analysis. In addition, adhesion assay, MTT and colony formation assays were performed for measuring adhesion and proliferation capacity. Cell cycle analysis via flow cytometry was conducted to explore cell cycle distribution. Western blot was used to detect pathway protein levels, and the pFAK (Y397) kit was used for focal adhesion kinase (FAK) activation.Results: We demonstrated that high expression of ZNF488 was significantly correlated with locoregional failure (P=0.018) and distant metastasis (P=0.001). Patients with high ZNF488 expression had poorer overall survival (P

Yuan Wang,1,* Yali Shao,1 Yuqing Gao,1 Guoran Wan,2 Dong Wan,3,* Huifeng Zhu,1 Yan Qiu,1 Xiyue Ye1 1Department of Chinese Medicine, College of Pharmaceutical Sciences and Traditional Chinese Medicine, Southwest University, Chongqing Engineering Research Center for Pharmacological Evaluation, Chongqing 400715, China; 2Department of Clinic Medicine, Chongqing Three Gorges Medical College, Chongqing 404120, China; 3Department of Emergency, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China *These authors contributed equally to this work Aim: To investigate the effects of catalpol on muscular atrophy induced by sciatic nerve crush injury (SNCI).Methods: Seventy male Kunming mice were randomized into five groups (n=10): model, sham, catalpol (Cat), rapamycin (Rapa), and catalpol+rapamycin (Rapa+Cat). The ratio of gastrocnemius muscle wet weight (right/left, R/L) between the operated leg (right) and the normal leg (left) was calculated, and acetylcholinesterase (AChE) immunohistochemistry assays were performed to observe the change of motor end plate (MEP), along with the sizes of denervated and innervated muscle fibers. The expression levels of LC3II, TUNEL, BAX/BCL-2, LC3II/LC3I and P62, Beclin1, mTOR, and p-mTOR (ser2448) proteins in muscle were examined by fluorescence immunohistochemistry or Western blotting.Results: Results show that catalpol improved the results of the grid walking tests by reducing the percentage of foot slips, which increased the gastrocnemius muscle wet weight (R/L), enhanced AChE expression at the MEP, and enlarged the section area of the muscle. The expression of LC3II and TUNEL was significantly inhibited by catalpol. The BAX/BCL-2 ratio was significantly increased in muscles of denervated and control groups. Lower LC3II/LC3I and BAX/BCL-2 ratios in denervated muscles were also detected after catalpol treatment.Conclusion: These results indicated that apoptosis and autophagy play a role in the regulation of denervation-induced muscle atrophy after SNCI, and catalpol alleviates muscle atrophy through the regulation of muscle apoptosis and autophagy via the mTOR signaling pathway. Keywords: catalpol, sciatic nerve crush injury, SNCI, denervated muscle atrophy, autophagy, muscle apoptosis

Background: Stroke is a leading cause of disability and death worldwide. Currently, there is a lack of clinically effective treatments for the brain damage following ischemic stroke. Catalpol is a bioactive compound derived from the traditional Chinese medicine Rehmannia glutinosa and shown to be protective in various neurological diseases. However, the potential roles of catalpol against ischemic stroke are still not completely clear., Purpose: This study aimed to further elucidate the protective effects of catalpol against ischemic stroke., Methods: A rat permanent middle cerebral artery occlusion (pMCAO) and oxygen-glucose deprivation (OGD) model was established to assess the effect of catalpol in vivo and in vitro, respectively. Behavioral tests were used to examine the effects of catalpol on neurological function of ischemic rats. Immunostaining was performed to evaluate the proliferation, migration and differentiation of neural stem cells (NSCs) as well as the angiogenesis in each group. The protein level of related molecules was detected by western-blot. The effects of catalpol on cultured NSCs as well as brain microvascular endothelial cells (BMECs) subjected to OGD in vitro were also examined by similar methods., Results: Catalpol attenuated the neurological deficits and improved neurological function of ischemic rats. It stimulated the proliferation of NSCs in the subventricular zone (SVZ), promoted their migration to the ischemic cortex and differentiation into neurons or glial cells. At the same time, catalpol increased the cerebral vessels density and the number of proliferating cerebrovascular endothelial cells in the infracted cortex of ischemic rats. The level of SDF-1α and CXCR4 in the ischemic cortex was found to be enhanced by catalpol treatment. Catalpol was also shown to promote the proliferation and migration of cultured NSCs as well as the proliferation of BMECs subjected to OGD insult in vitro. Interestingly, the impact of catalpol on cultured cells was inhibited by CXCR4 inhibitor AMD3100. Moreover, the culture medium of BMECs containing catalpol promoted the proliferation of NSCs, which was also suppressed by AMD3100., Conclusion: Our data demonstrate that catalpol exerts neuroprotective effects by promoting neurogenesis and angiogenesis via the SDF-1α/CXCR4 pathway, suggesting the therapeutic potential of catalpol in treating cerebral ischemia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier GmbH.)

The Shexiang Zhuifeng Zhitong Ointment with the effects of dispelling wind, removing dampness, dissipating cold, and relieving pain is used for treating arthralgia, muscular pain, and sprain pain caused by cold-dampness obstruction. To evaluate the efficacy and safety of Shexiang Zhuifeng Zhitong Ointment in relieving the pain due to knee osteoarthritis(syndrome of cold-dampness obstruction), a randomized, double-blind, parallel controlled, multicenter clinical trial was conducted. The stratified randomization method was used to randomize the 240 subjects into a treatment group and a control group in a ratio of 1∶1. In each group, 60 patients received external application for 12 h and the other 60 patients received external application for 6 h. The treatment group received external application of Shexiang Zhuifeng Zhitong Ointment, while the control group received external application of Shexiang Zhuifeng Ointment. The treatment lasted for 21 days in both groups. Follow-up was conducted on days 7, 14, and 21 of treatment. The results based on the full analysis set were as follows.(1)In visual analog scale(VAS) score, the mean difference in the VAS score between baseline and 12 h post-treatment was 3.02 in the treatment group and 2.31 in the control group, with a significant difference(P<0.05). The mean difference in the VAS score between baseline and 6 h post-treatment was 3.19 in the treatment group and 2.48 in the control group, with a significant difference(P<0.05).(2)Response rate in terms of VAS score, after treatment for 12 h, the response rate was 93.22% in the treatment group and 73.33% in the control group, with a significant difference(P<0.05). After treatment for 6 h, theresponse rate in the treatment group was 88.33%, which was higher than that(63.33%) in the control group(P<0.05).The results showed that Shexiang Zhuifeng Zhitong Ointment applied for 12 and 6 h effectively relieved the knee joint pain of patients with knee osteoarthritis due to cold-dampness obstruction, as demonstrated by the reduced VAS score, Western Ontario and McMaster Universities Arthritis Index(WOMAC), stiffness, and joint function score. Moreover, Shexiang Zhuifeng Zhitong Ointment outperformed the positive control Shexiang Zhuifeng Ointment in terms of reducing the VAS score, demonstrating a definitetherapeutic effect on the pain due to knee osteoarthritis(syndrome of cold-dampness obstruction).In addition, Shexiang Zhuifeng Zhitong Ointment did not cause other adverse reactions except for mild allergic reactions, which were common in the external application of traditional Chinese medicine plasters on the skin, inseveral patients.Neither other adverse reactions nor abnormalities of liver and kidney functions and electrocardiogram were observed. This ointment had high safety and could be popularized in clinical application.

Ethnopharmacological Relevance: Cisplatin (CP) results in acute kidney injury (AKI) and negatively affects patients' therapy and survival. The dried rhizome of Gastrodia elata Blume has been used to treat clinical kidney diseases. Gastrodin (GAS) is an active ingredient of the G. elata tuber. It is unknown whether GAS can alleviate CP-induced AKI., Aim of the Study: This study aimed to investigate whether GAS, an active ingredient of G. elata Blume, can alleviate CP-induced AKI and to explore its underlying mechanisms., Materials and Methods: Experiments were conducted with a CP-induced AKI mouse model and an immortalized human renal tubular epithelial cell line (HK-2). Serum creatinine, Periodic acid-Schiff staining, tissue iron, glutathione, malondialdehyde, and 4-Hydroxynonenal were detected in serum and kidney samples to observe whether GAS inhibits CP-induced tubule ferroptosis. The drug target was verified by detecting the effects of GAS on sirtuin-1 (SIRT1) activity in vitro. Transcriptional regulation of glutathione peroxidase 4 (GPX4) by forkhead box O3A (FOXO3A) was verified by siRNA knockdown, overexpression, and chromatin immunoprecipitation. The effects of FOXO3A, SIRT1, and GAS on CP-induced ferroptosis were measured with propidium iodide, dihydroethidium, monobromobimane, and dipyrromethene boron difluoride staining in HK-2 cells. The relationship between GAS and the SIRT1/FOXO3A/GPX4 pathway was studied using Western blotting., Results: GAS treatment inhibited CP-induced reactive oxygen species, lipid peroxidation, and tubule death in the cell and animal models. GAS activated SIRT1 in vitro. The SIRT1 inhibitor blocked the protective role of GAS in reducing lipid peroxidation in HK-2 cells. FOXO3A transcriptionally regulated GPX4 expression and inhibited CP-induced cell ferroptosis. Compared to CP-damaged mouse kidneys, GAS-treated mice demonstrated significantly increased SIRT1 and GPX4 expression levels, decreased CP-induced acetylation of FOXO3A, and inhibited lipid peroxidation and cell death., Conclusions: GAS alleviated CP-induced AKI by inhibiting ferroptosis via the SIRT1/FOXO3A/GPX4 signaling pathway. The results offer new insights into the development of new anti-AKI drugs from traditional Chinese medicine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Plasmodiophora brassicae ( P. brassicae ) is a soil-born pathogen worldwide and can infect most cruciferous plants, which causes great yield decline and economic losses. It is not well known how microbial diversity and community composition change during P. brassicae infecting plant roots. Here, we employed a resistant and a susceptible pakchoi cultivar with and without inoculation with P. brassicae to analyze bacterial and fungal diversity using 16S rRNA V3-V4 and ITS_V1 regions, respectively. 16S rRNA V3-V4 and ITS_V1 regions were amplified and sequenced separately. Results revealed that both fungal and bacterial diversity increased, and composition was changed in the rhizosphere soil of the susceptible pakchoi compared with the resistant cultivar. In the four groups of R_mock, S_mock, R_10d, and S_10d, the most relatively abundant bacterium and fungus was Proteobacteria, accounting for 61.92%, 58.17%, 48.64%, and 50.00%, respectively, and Ascomycota , accounting for 75.11%, 63.69%, 72.10%, and 90.31%, respectively. A total of 9488 and 11,914 bacteria were observed uniquely in the rhizosphere soil of resistant and susceptible pakchoi, respectively, while only 80 and 103 fungi were observed uniquely in the correlated soil. LefSe analysis showed that 107 and 49 differentially abundant taxa were observed in bacteria and fungi. Overall, we concluded that different pakchoi cultivars affect microbial diversity and community composition, and microorganisms prefer to gather around the rhizosphere of susceptible pakchoi. These findings provide a new insight into plant-microorganism interactions.

Background: Immune-checkpoint inhibitors (ICIs) have revolutionized the treatment of hepatocellular carcinoma (HCC). However, long-term survival outcomes and treatment response of HCC patients undergoing immunotherapy is unpredictable. The study aimed to evaluate the role of alpha-fetoprotein (AFP) combined with neutrophil-to-lymphocyte ratio (NLR) to predict the prognosis and treatment response of HCC patients receiving ICIs., Methods: Patients with unresectable HCC who received ICI treatment were included. The HCC immunotherapy score was developed from a retrospective cohort at the Eastern Hepatobiliary Surgery Hospital to form the training cohort. The clinical variables independently associated with overall survival (OS) were identified using univariate and multivariate Cox regression analysis. Based on multivariate analysis of OS, a predictive score based on AFP and NLR was constructed, and patients were stratified into three risk groups according to this score. The clinical utility of this score to predict progression-free survival (PFS) and differentiate objective response rate (ORR) and disease control rate (DCR) was also performed. This score was validated in an independent external validation cohort at the First Affiliated Hospital of Wenzhou Medical University., Results: Baseline AFP ≤ 400 ng/ml (hazard ratio [HR] 0.48; 95% CI, 0.24-0.97; P = 0.039) and NLR ≤ 2.77 (HR 0.11; 95% CI, 0.03-0.37; P<0.001) were found to be independent risk factors of OS. The two labolatory values were used to develop the score to predict survival outcomes and treatment response in HCC patients receiving immunotherapy, which assigned 1 point for AFP > 400 ng/ml and 3 points for NLR > 2.77. Patients with 0 point were classified as the low-risk group. Patients with 1-3 points were categorized as the intermediate-risk group. Patients with 4 points were classified as the high-risk group. In the training cohort, the median OS of the low-risk group was not reached. The median OS of the intermediate-risk group and high-risk group were 29.0 (95% CI 20.8-37.3) months and 16.0 (95% CI 10.8-21.2) months, respectively (P < 0.001). The median PFS of the low-risk group was not reached. The median PFS of the intermediate-risk group and high-risk group were 14.6 (95% CI 11.3-17.8) months and 7.6 (95% CI 3.6-11.7) months, respectively (P < 0.001). The ORR and DCR were highest in the low-risk group, followed by the intermediate-risk group and the high-risk group (P < 0.001, P = 0.007, respectively). This score also had good predictive power using the validation cohort., Conclusion: The HCC immunotherapy score based on AFP and NLR can predict survival outcomes and treatment response in patients receiving ICI treatments, suggesting that this score could serve as a useful tool for identification of HCC patients likely to benefit from immunotherapy., (© 2023. The Author(s).)

Exploring flexible electronics is on the verge of innovative breakthroughs in terahertz (THz) communication technology. Vanadium dioxide (VO 2 ) with insulator-metal transition (IMT) has excellent application potential in various THz smart devices, but the associated THz modulation properties in the flexible state have rarely been reported. Herein, we deposited an epitaxial VO 2 film on a flexible mica substrate via pulsed-laser deposition and investigated its THz modulation properties under different uniaxial strains across the phase transition. It was observed that the THz modulation depth increases under compressive strain and decreases under tensile strain. Moreover, the phase-transition threshold depends on the uniaxial strain. Particularly, the rate of the phase transition temperature depends on the uniaxial strain and reaches approximately 6 °C/% in the temperature-induced phase transition. The optical trigger threshold in laser-induced phase transition decreased by 38.9% under compressive strain but increased by 36.7% under tensile strain, compared to the initial state without uniaxial strain. These findings demonstrate the uniaxial strain-induced low-power triggered THz modulation and provide new insights for applying phase transition oxide films in THz flexible electronics.

African swine fever virus (ASFV) causes feverous and hemorrhagic disease of domestic pigs and European wild boars with high mortality, yet no commercial vaccine is currently available. Several ASFV strains with natural deletion or gene-targeted knockout of multiple MGF360 and MGF505 genes are attenuated in vitro and in vivo, and can offer full protection against homologous challenge. However, the mechanisms underlying the protection are not fully understood. This study aims to investigate the effects of MGF360-12L of ASFV-SY18 on the cGAS-STING signaling pathway and explore the potential mechanisms. We identified that ASFV-SY18 MGF360-12L could inhibit cGAS-STING, TBK1, or IRF3-5D-stimulated IFN-β expression and ISRE activation. Specifically, MGF360-12L inhibits both the activation of PRD(III-I) in a dose-dependent manner, and suppresses the exogenous expression of TBK1 and IRF3-5D. MGF360-12L could block NF-κB activation induced by overexpression of cGAS-STING, TBK1, IKKβ. Downstream of the IFN-β signaling, MGF360-12L blocks the ISRE promoter activation by reducing total protein level of IRF9. Moreover, MGF360-12L protein can inhibit IFN-β-mediated antiviral effects. In conclusion, our findings suggest that MGF360-12L is a multifunctional immune-evasion protein that inhibits both the expression and effect of IFN-β, which could partially explain the attenuation of relevant gene-deleted ASFV strains, and shed light on the development of efficient ASFV live attenuated vaccines in the future., (Copyright© by the Polish Academy of Sciences.)

Background and Aims: The efficacy and safety of systemic atezolizumab and bevacizumab (atezo/bev) in treatment of patients with unresectable hepatocellular carcinoma (HCC) have been demonstrated. However, the efficacy of this treatment in patients with HCC and extrahepatic portal vein tumor thrombus (ePVTT) is not satisfactory. This study aimed to study the efficacy and safety of combining intensity-modulated radiotherapy (IMRT) with systemic atezo/bev in treatment of these patients., Methods: This multicenter prospective study included patients with ePVTT treated with IMRT combined with atezo/bev from March to September 2021 in three centers in China. The outcomes of this study included objective response rate (ORR), overall survival (OS), progression-free survival (PFS), time to progression (TTP), and association between response and tumor mutational burden (TMB). Treatment-related adverse events (TRAEs) were analyzed to assess safety., Results: Of 30 patients in this study, the median follow-up was 7.4 months. Based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, the ORR was 76.6%, the median OS for the entire cohort was 9.8 months, the median PFS was 8.0 months, and the median TTP was not reached. This study failed to establish a significant correlation between TMB with any of the following outcomes, including ORR, OS, PFS or TTP. The most common TRAEs at all levels were neutropenia (46.7%), and the most common grade 3/4 TRAE was hypertension (16.7%). There was no treatment-related deaths., Conclusions: IMRT combined with atezo/bev showed encouraging treatment efficacy with an acceptable safety profile, making this treatment to be a promising option for HCC patients with ePVTT. Further studies are required to support the findings of this preliminary study., Clinical Trial Registration: http://www.chictr.org.cn, Identifier ChiCTR2200061793., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Xiang, Yu, Cheng, Liu, Zhong, Feng, Ni, Zhu, Pan, Li, Liang, Zhou, Meng, Lau and Cheng.)

β decay of proton-rich nuclei plays an important role in exploring isospin mixing. The β decay of ^{26}P at the proton drip line is studied using double-sided silicon strip detectors operating in conjunction with high-purity germanium detectors. The T=2 isobaric analog state (IAS) at 13 055 keV and two new high-lying states at 13 380 and 11 912 keV in ^{26}Si are unambiguously identified through β-delayed two-proton emission (β2p). Angular correlations of two protons emitted from ^{26}Si excited states populated by ^{26}P β decay are measured, which suggests that the two protons are emitted mainly sequentially. We report the first observation of a strongly isospin-mixed doublet that deexcites mainly via two-proton decay. The isospin mixing matrix element between the ^{26}Si IAS and the nearby 13 380-keV state is determined to be 130(21) keV, and this result represents the strongest mixing, highest excitation energy, and largest level spacing of a doublet ever observed in β-decay experiments.

Purpose: This study aimed to assess the efficacy and safety of a triple therapy that comprises transarterial chemoembolization (TACE), antiangiogenic-targeted therapy, and programmed death-1 (PD-1) inhibitors in a real-world cohort of patients with unresectable hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT)., Methods: Consecutive patients treated with TACE combined with antiangiogenic therapy and PD-1 inhibitors at the Eastern Hepatobiliary Surgery Hospital between June 2019 and May 2021 were enrolled. The baseline characteristics and treatment course of the patients were recorded. The tumor response was evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and HCC-specific modified RECIST (mRECIST). The overall survival (OS) and progression-free survival (PFS) of the patients were analyzed using the Kaplan-Meier method. Adverse events (AEs) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0., Results: As of the data cutoff on 30 August 2021, the median follow-up time was 10.0 (3.9-28.4) months. A total of 39 eligible patients were included. The objective response rate (ORR) and the disease control rate (DCR) were 35.9% and 74.4% according to the RECIST 1.1, and 48.7% and 84.6% according to mRECIST criteria, respectively. The median OS and PFS were 14.0 and 9.2 months, respectively. Moreover, 34 (87.2%) patients experienced at least one treatment-related AE and 8 (20.5%) patients experienced grade 3/4 treatment-related AEs. The most common treatment- and laboratory-related AEs were hypertension (46.2%) and decreased albumin (53.8%), respectively. No treatment-related mortality occurred during the study period., Conclusions: TACE combined with antiangiogenic-targeted therapy and immune checkpoint inhibitors may have promising anticancer activity in unresectable HCC patients with PVTT. AEs were manageable, with no unexpected overlapping toxicities., 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 Feng, Liu, Fu, Chai, Sun, Wang, Cheng, Zhu, Xiang, Zhou, Shi, Guo, Zhai and Cheng.)

Study Design: Prospective cohort study., Objective: To assess the differences in the clinical and radiological outcomes between oblique lateral interbody fusion (OLIF) and minimally invasive transforaminal lumbar interbody fusion (MI-TLIF)., Summary of Background Data: Nowadays, there is still a controversy regarding whether OLIF is superior to MI-TLIF in the management of degenerative lumbar disease., Methods: Between August 3, 2019 and February 3, 2020, 137 patients were assigned to OLIF or MI-TLIF at their request and the surgeon's discretion: 71 in the OLIF group and 66 in the MI-TLIF group. The perioperative data, patient-reported outcomes, radiographic outcomes, and complications were compared between the two groups., Results: The OLIF group showed shorter operation time (110.5 vs.183.8 minutes, P < 0.001), lesser estimated blood loss (123.1 vs. 232.0 mL, P < 0.001), shorter length of hospital stay (5.5 vs. 6.7 days, P < 0.001), and lower serum creatine kinase (CK) (1 day postoperatively) (376.0 vs. 541.8 IU/L, P < 0.01) than that of MI-TLIF group. Both groups showed no significant differences in the visual analog scale (VAS) scores of lower back and leg pain and the Oswestry Disability Index (ODI) scores preoperatively and at 1, 3, and 12 months postoperatively, respectively (P > 0.05). Compared with the MI-TLIF group, the OLIF group showed better restoration of disc height (DH) (4.7/4.6/4.7 vs. 3.7/3.7/3.7 mm, P < 0.01) and lumbar lordosis angle (LLA) (10.5°/10.8°/11.1° vs. 5.8°/5.7°/5.3°, P < 0.001), but not the value of segmental lordosis angle (SLA) (P > 0.05) at 1 day, 1 month, and 1 year postoperatively, respectively. The complication rate of OLIF was higher than that of MI-TLIF (29.4% vs. 9.7%, P < 0.01)., Conclusion: Compared with MI-TLIF, OLIF showed similar results in terms of patient-reported outcomes, restoration of SLA and fusion rate, and superior results with respect to restoration of DH and LLA, operation time, estimated blood loss, length of hospital stay, and serum CK levels (1 day postoperatively). Even though the complication rate of OLIF is higher than that of MI-TLIF, it does not bring persistent and substantial damage to the patients.Level of Evidence: 3., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Geniposide is a bioactive iridoid glucoside derived from Gardenia jasminoides that has proven anti-inflammatory effects against acute lung injury. The aim of this study was to determine whether geniposide could protect pulmonary arterial smooth muscle cells (PASMCs) from lipopolysaccharide (LPS)-induced injury and to explore the participation of α7 nicotinic acetylcholine receptor (α7nAChR), which was previously reported to suppress pro-inflammatory cytokine production in LPS-stimulated macrophages. In the present study, rat PASMCs were isolated and stimulated using LPS. The effect of geniposide on LPS-induced PASMC injury was then explored. Geniposide exerted anti-apoptotic and anti-inflammatory effects on LPS-treated PASMCs, as demonstrated by the downregulation of pro-apoptotic proteins and pro-inflammatory cytokines, respectively. Furthermore, the α7nAChR agonist PNU282987 accentuated the protective effect of geniposide against LPS-induced injury in PASMCs by inhibiting toll-like receptor-4/myeloid differentiation primary response 88 (TLR-4/MyD88) signaling and downregulating nuclear factor (NF)-κB expression. Conversely, methyllycaconitine, an inhibitor of α7nAChR, attenuated the effects of geniposide. These findings collectively suggested that in conjunction with geniposide, the activation of α7nAChR may contribute to further mitigating LPS-induced PASMC apoptosis and inflammation. In addition, the underlying mechanisms critically involve the NF-κB/MyD88 signaling axis. These results may provide novel insights into the treatment and management of lung diseases via geniposide administration., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Shen et al.)

In order to standardize the clinical diagnosis and treatment decision-making with traditional Chinese medicine for pa-tients of coronavirus disease 2019(COVID-19) and put the latest clinical study evidence into clinical practice, the international trust-worthy traditional Chinese medicine recommendations( TCM Recs) working group started the compilation of Living Evidence-based Guideline for Combination of Traditional Chinese and Western Medicine for Treatment of COVID-19 on the basis of the standards and re-quirements of WHO handbook, GRADE and RIGHT. This proposal mainly introduces the formulation methods and processes of the living guidelines in details, such as the composition of the working group, the collection and identification of clinical issues and out-comes, the production of the living systematic review and the consensus of recommendations. The guidelines will continue to monitor the clinical study evidences of TCM in the prevention and treatment of COVID-19, and conduct regular evidence updating, retrieval and screening. When there is new study evidence, the steering committee will evaluate the possibility of the evidence to change clinical practice or previous recommendations, so as to decide whether the recommendations for the guidelines shall be implemented or upda-ted. The main criteria considered in the guideline updating are as follows:(1) There are new high-quality randomized controlled trial(RCT) evidences for TCM uninvolved in the previous edition of the guidelines;(2) as for the TCM involved in the guidelines, living sys-tematic review shows that new evidence may change the direction or strength of the existing recommendations. The specific implementation of the living evidence-based guidelines will take this proposal as the study basis and framework, in order to ensure the standardization of the formulation process and methods. This will be the first exploration of the methodology for living guidelines in the field of TCM.

Evaluating the impacts of human activity on river runoff has important implications for regional water resource management. Here, we used seven tree-ring width chronologies to establish a regional mean tree-ring width chronology from the northern mountain of Delingha, Qaidam Basin. We conducted the correlation, moving correlation and regression analysis of regional mean tree-ring width chronology with runoff data from Bayin River gauge station. Then, we stimulated the June runoff of Bayin River from 1956 to 2002. The results showed that the highest correlation coefficient was found for June runoff ( r =0.63, P <0.01), and their moving correlation coefficient decreased after 1986. Based on the stable relationship between tree-ring width chronology and the June runoff during 1956-1986, we built the reconstruction function, which was explained 50.8% of observed runoff. The stimulated runoff during 1987 to 2002 was significantly higher than the observed runoff (3.01 m 3 ·s -1 , P <0.001). These results indicated that human activity from the upper river had significant impacts on Bayin River runoff. Human activity should be considered as an important factor to protect security of sustainable water resource utilization for future water resource development and utilization in Bayin River region.

Oblique lateral lumbar interbody fusion (OLIF) has been extensively used, with satisfactory outcomes for the treatment of degenerative lumbar disease. This article aims to demonstrate a modified lateral approach, also known as the anteroinferior psoas (AIP) technique for OLIF, which is expected to enhance security by operating under direct vision. The core procedures of our technique are as follows. First, a minimal skin incision is recommended 2 cm backward compared with the normal incision of OLIF, facilitating the oblique placement of the working channel and the orthogonal maneuver for the cage placement. Second, two special custom-made retractors, as an alternative to the index finger, are used to pull the psoas muscle to the dorsal side and pull the abdominal organs together with extraperitoneal fate to the ventral side under direct visualization, making the exposure of the working channel convenient and safe and avoiding radiation exposure. Third, the anterior border of the psoas is bluntly dissected and retracted backwards, obviously enlarging the retroperitoneal anatomic corridor and then expanding clinical indications of OLIF. The benefits of this technique include that it has a short learning curve, satisfactory clinical outcomes, and low risk of perioperative complications., (© 2021 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

In view of the influence of variability of low-frequency noise frequency on noise prevention in real life, we present a novel two-dimensional tunable phononic crystal plate which is consisted of lead columns deposited in a silicone rubber plate with periodic holes and calculate its bandgap characteristics by finite element method. The low-frequency bandgap mechanism of the designed model is discussed simultaneously. Accordingly, the influence of geometric parameters of the phononic crystal plate on the bandgap characteristics is analyzed and the bandgap adjustability under prestretch strain is further studied. Results show that the new designed phononic crystal plate has lower bandgap starting frequency and wider bandwidth than the traditional single-sided structure, which is due to the coupling between the resonance mode of the scatterer and the long traveling wave in the matrix with the introduction of periodic holes. Applying prestretch strain to the matrix can realize active realtime control of low-frequency bandgap under slight deformation and broaden the low-frequency bandgap, which can be explained as the multiple bands tend to be flattened due to the localization degree of unit cell vibration increases with the rise of prestrain. The presented structure improves the realtime adjustability of sound isolation and vibration reduction frequency for phononic crystal in complex acoustic vibration environments.

Background: Arthroscopic repair is recommended for young patients with full-thickness rotator cuff tears (RCTs), but the healing rates have raised concerns. The Southern California Orthopedic Institute (SCOI) row method has been developed based on greater than 3 decades of experience with excellent clinical outcomes; however, studies with a focus on the younger patient population are limited in number. The current study assessed the short-term clinical outcome and the initial tendon-to-bone healing in a young cohort after repair of a full-thickness RCT using the SCOI row method., Methods: A retrospective cohort study was performed. Patients < 55 years of age who had a full-thickness RCT and underwent an arthroscopic repair using the SCOI row method were reviewed. Clinical outcomes were assessed at baseline, and 3 and 6 months post-operatively. The visual analog scale (VAS), University of California at Los Angeles (UCLA) scale, and Constant-Murley score were completed to assess pain and function. Active range of motion was also examined, including abduction and flexion of the involved shoulder. A preoperative MRI was obtained to assess the condition of the torn tendon, while 3- and 6-month postoperative MRIs were obtained to assess tendon-to-bone healing. Repeated measurement ANOVA and chi-square tests were used as indicated., Results: Eighty-nine patients (57 males and 32 females) with a mean age of 44.1 ± 8.6 years who met the criteria were included in the study. Compared with baseline, clinical outcomes were significantly improved 3 and 6 months postoperatively based on improvement in the VAS, UCLA score, and Constant-Murley score, as well as range of motion. Greater improvement was also noted at the 6-month postoperative assessment compared to the 3-month postoperative assessment. Three- and six-month postoperative MRIs demonstrated intact repairs in all shoulders and footprint regeneration, which supported satisfactory tendon-to-bone healing. The mean thickness of regeneration tissue was 7.35 ± 0.76 and 7.75 ± 0.79 mm as measured from the 3- and 6-month MRI (P = 0.002). The total satisfactory rate was 93.3 %., Conclusions: Arthroscopic primary rotator cuff repair of a full-thickness RCT using the SCOI row method in patients < 55 years of age yields favorable clinical outcomes and early footprint regeneration.

Background: Although excellent clinical outcomes of supercapsular percutaneously assisted total hip arthroplasty (SuperPath) have been reported, the peri-operative blood loss has rarely been reported. The current study determined the blood loss during SuperPath and compared the blood loss with conventional posterolateral total hip arthroplasty (PLTH)., Methods: This retrospective study enrolled patients who underwent unilateral primary THA between January 2017 and December 2019. The demographic data, diagnoses, affected side, radiographic findings, hemoglobin concentration, hematocrit, operative time, transfusion requirements, and intra-operative blood loss were recorded. The peri-operative blood loss was calculated using the OSTHEO formula. Blood loss on the 1st, 3rd, and 5th post-operative days was calculated. Hidden blood loss (HBL) was determined by subtracting the intra-operative blood loss from the total blood loss., Results: Two hundred sixty-three patients were included in the study, 85 of whom were in the SuperPath group and 178 in the posterolateral total hip arthroplasty (PLTH) group. Patient demographics, diagnoses, affected side, operative times, and pre-operative hemoglobin concentrations did not differ significantly between the two groups (all P > 0.05). Compared to the PLTH group, the SuperPath group had less blood loss, including intra-operative blood loss, 1st, 3rd, and 5th post-operative days blood loss, and HBL (all P < 0.05). Total blood loss and HBL was 790.07 ± 233.37 and 560.67 ± 195.54 mL for the SuperPath group, respectively, and 1141.26 ± 482.52 and 783.45 ± 379.24 mL for the PLTH group. PLTH led to a greater reduction in the post-operative hematocrit than SuperPath (P < 0.001). A much lower transfusion rate (P = 0.028) and transfusion volume (P = 0.019) was also noted in the SuperPath group., Conclusion: SuperPath resulted in less perioperative blood loss and a lower transfusion rate than conventional PLTH.

Aims: To explore the biological function and mechanism of Syntaxin2 (STX2) in Colorectal cancer (CRC) proliferation., Main Methods: A series of gain- and loss-of-function analysis were conducted the to explore the biological function of STX2 in CRC proliferation in vivo and in vitro. Western blot, Co-immunoprecipitation (Co-IP) and the functional analyses were taken to analyze the regulative role of STX2 on Exosome Complex 4 (EXOSC4) in CRC proliferation; Immunohistochemistry (IHC) and Real-time quantitative polymerase chain reaction (qPCR) were used to further verify the relationship between the expression of STX2 and EXOSC4 in human CRC samples., Key Findings: Our study revealed that the over-expression of STX2 promoted CRC proliferation, while knockdown of STX2 repressed CRC proliferation; STX2 promoted CRC proliferation via increasing EXOSC4 protein; There was a positive correlation between STX2 and EXOSC4 expression., Significance: The current data verify that STX2 drives the proliferation of CRC via increasing the expression of EXOSC4., (Copyright © 2020. Published by Elsevier Inc.)

Objective: To study the Polymorphism of the human platelet antigen(HPA) gene 1-17 and human leukocyte antigen(HLA) gene-A and B locus in Shandong Han population., Methods: A total of 962 samples from routine voluntary platelet donors were genotyped for HPA1-17 system and HLA-A site, B by PCR-SSP and PCR-SSOP respectively．Gene frequencies were calculated by counting. HPA1-17 and HLA genotype combinations were analyzed by Arelequin 3.5., Results: The gene frequencies of HPA-la, -1b, HPA-2a, -2b, HPA-3a, -3b, HPA-4a, -4b, HPA-5a, -5b, HPA-6a, -6b, HPA-15a, -15b were 0.9918, 0.0082, 0.9419, 0.0592, 0.5841, 0.4174, 0.9969, 0.0031, 0.9892, 0.0108, 0.9835, 0.0175,0.5488 and 0.4512, respectively． The most common HPA genotype combination was HPA-(1, 2, 4, 5, 6, 7-14, 16, 17) aa-3ab-15ab (0.2048). Moreover, HLA-A*2(0.3094) and HLA-B*13(0.1513) showed the highest frequency in their respective locus. The most common HLA genotype combination was HLA-A*2-B*13(0.1397) ., Conclusion: Distributions of HPA and HLA show high polymorphism in Shandong Han population. The ethnic and territorial difference of HPA distribution is also confirmed. It is imperative to establish local genetic database of volunteer platelet donors.

A dynamic covalent system of the picolyl heterocyclic amino aminals has been studied. The aminals are characterized as a metastable species and easily switch to other forms via external stimuli. The solvent, temperature, acid-base and substituent effects have been examined to evaluate the dynamic covalent system. The results reveal that a more polar solvent, a lower temperature, basic conditions and an electron-withdrawing moiety contribute to the stabilities of aminals. The existence of the n → π* interaction between acetonitrile and the C[double bond, length as m-dash]N moiety makes the N -pyrimidyl imine (4c and 4d) yield higher in CD 3 CN. In a similar fashion, all aminals tend to convert to the corresponding hemiaminal ethers in a methanol environment. According to these findings, we successfully synthesized the following species: (a) N -2-picolylpyrimidin-2-amine 6c obtained by reduction using acetonitrile as the specific solvent; (b) a picolyl aromatic amino aminal 3e prepared from 2-pyridinecarboxaldehyde and the electron withdrawing 2-methoxy-5-nitroaniline., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

In the multi-effect evaporation salt making process, the smooth operation of the salt making process is crucial. As the salt production process continues, many unstable factors will cause the salt production process not to proceed smoothly. These factors can be discovered in advance by predicting the salt production data, thus, it is of great significance to predict the multi-effect evaporation salt production data. In the process of multi-effect evaporation and salt production, the multiple salt-making devices make the influence between the parameters closer, and the influence of a single parameter on itself is sometimes ductile. Therefore, the data of multi-effect evaporation and salt production have the characteristics of high dimensions, high complexity and temporal information. If the historical salt production data is used for data prediction directly, the prediction model will take a long time and the prediction effect is not good. Thus, how to predict the multi-effect evaporation salt production data is the main research problem of this paper. In view of the above problems, according to the characteristics of multi-effect evaporation salt production data, this paper analyzes and improves the self encoder for feature extraction of multi effect-evaporation salt production data, so as to solve the problem of high dimensions and high complexity of salt production data. On this basis, combined with the time-series information contained in the salt production data, a multi-effect evaporation salt production data prediction model is proposed based on long-term and short-term memory cycle neural network to solve the prediction problem of time-series salt production data. Experiments show that the prediction model can predict and prevent the problems in salt production line in advance. It has a certain theoretical research value and application value in the intelligent production process and production line optimization of salt chemical industry.

The microbiome associated with brown planthopper (BPH) plays an important role in mediating host health and fitness. Characterization of the microbial community and its structure is prerequisite for understanding the intricate symbiotic relationships between microbes and host insect. Here, we investigated the bacterial and fungal communities of BPH at different developmental stages using high-throughput amplicon sequencing. Our results revealed that both the bacterial and fungal communities were diverse and dynamic during BPH development. The bacterial communities were generally richer than fungi in each developmental stage. At 97% similarly, 19 phyla and 278 genera of bacteria were annotated, while five fungal phyla comprising 80 genera were assigned. The highest species richness for the bacterial communities was detected in the nymphal stage. The taxonomic diversity of the fungal communities in female adults was generally at a relatively higher level when compared to other developmental stages. The most dominant phylum of bacteria and fungi at each developmental stage all belonged to Proteobacteria and Ascomycota, respectively. A significantly lower abundance of bacterial genus Acinetobacter was recorded in the egg stage when compared to other developmental stages, while the dominant fungal genus Wallemia was more abundant in the nymph and adult stages than in the egg stage. Additionally, the microbial composition differed between male and female adults, suggesting that the microbial communities in BPH were gender-dependent. Overall, our study enriches our knowledge on the microbial communities associated with BPH and will provide clues to develop potential biocontrol techniques against this rice pest., (© 2019 Institute of Zoology, Chinese Academy of Sciences.)

Background: Numerous biomechanical and clinical studies comparing different techniques for rotator cuff repair have been reported, yet universal consensus regarding the superior technique has not achieved. A medially-based single-row with triple-loaded suture anchor (also referred to as the Southern California Orthopedic Institute [SCOI] row) and a suture-bridge double-row (SB-DR) with Push-Locks have been shown to result in comparable improvement in treating rotator cuff tear, yet the biomechanical difference is unknown. The purpose of the current study was to determine whether a SCOI row repair had comparable initial biomechanical properties to a SB-DR repair., Methods: Six matched pairs of fresh-frozen cadaveric shoulders with full-thickness supraspinatus tendon tears we created were included. Two different repairs were performed for each pair (SCOI row and SB-DR methods). Specimens were mounted on a material testing machine to undergo cyclic loading, which was cycled from 10 to 100 N at 1 Hz for 500 cycles. Construct gap formation was recorded at an interval of 50 cycles. Samples were then loaded to failure and modes of failure were recorded. Repeated-measures analysis of variance and pair-t test were used for statistical analyses., Results: The construct gap formation did not differ between SCOI row and SB-DR repairs (P = 0.056). The last gap displacement was 1.93 ± 0.37 mm for SCOI row repair, and 1.49 ± 0.55 mm for SB-DR repair. The tensile load for 5 mm of elongation and ultimate failure were higher for SCOI row repair compared to SB-DR repair (P = 0.011 and 0.028, respectively). The ultimate failure load was 326.34 ± 11.52 N in the SCOI row group, and 299.82 ± 27.27 N in the SB-DR group. Rotator cuff repair with the SCOI row method failed primarily at the suture- tendon interface, whereas pullout of the lateral row anchors was the primary mechanism of failure for repair with the SB-DR method., Conclusion: Rotator cuff repair with the SCOI row method has superior biomechanical properties when compared with the SB-DR method. Therefore, SCOI row repair using a medially-based single-row technique with triple-loaded suture anchor is recommended to improve the initial strength in treating full-thickness rotator cuff tears.

The microstructure evolution, tensile properties and work-hardening behavior of AA2219 alloy reinforced by in situ nanosized TiB 2 particles were studied in this paper. The observation indicated an impeded recrystallization of the matrix alloy by nanosized TiB 2 particles, and the hybrids of nanosized TiB 2 particles and Al 2 Cu phases located at the grain boundary hindered the grain growth. Meanwhile, a large amount fiber textures of <111>//RD (Rolling direction), <110>//RD, <100>//RD <111>//ND (Normal direction), <110>//ND and <100>//ND were detected in nanosized TiB 2 /AA2219 composite. Tensile test results exhibited a combination of good strength and ductility of the present composite whose yield strength and tensile strength were 11.4% and 5.8% higher than those of the alloy, while its fracture strain increased slightly. Meanwhile, the correlation between this modified microstructure of nanosized TiB 2 particles and comprehensive mechanical properties was established. This study provides a new insight into the fabrication and strengthening behaviors of Al matrix composites reinforced by in situ nanoparticles.

To investigate the ecological mechanisms of the bacterial response to human disturbance in micro-polluted water ecosystems, we studied the relationship between the environmental factors and bacterial community development in the incoming water and various areas of a reservoir based on an ecological null model. The results showed that the phylogenetic clustering of bacterial communities was more dispersed than expected (the single-sample t -test of SES.MNTD has a 95% lower confidence limit of 9.79). Temperature is an important environmental factor affecting community phylogeny. The relative importance of stochastic and deterministic processes in the bacterial community succession of different samples showed seasonal characteristics. The bacterial community succession in spring, summer, and autumn samples was dominated by random and deterministic processes. NH 4 + -N is the main environmental factor affecting the relative importance of random and deterministic processes. When the concentration of NH 4 + -N is 0.06-0.40 mg ·L -1 , the bacterial community succession is dominated by random processes; when the concentration is 0.40-0.80 mg ·L -1 , it is dominated by both random and deterministic processes. Dispersal limitation (61.68%) and heterogeneous selection (26.65%) played important roles in bacterial community changes at different sampling points in the study area.

Background: Paclitaxel plays a pivotal role in the chemotherapy of breast cancer, but resistance to this drug is an important obstacle in the treatment. It is reported that microRNA-152-3p (miR-152-3p) is involved in tamoxifen resistance in breast cancer, but whether it is involved in paclitaxel resistance in breast cancer remains unknown. Materials and methods: We examined the expression of miR-152-3p in breast cancer tissues and cells by qRT-PCR. After transfecting paclitaxel-resistant MCF-7/TAX cells with miR-152-3p mimics, we analyzed the function of miR-152-3p in these cells by MTT assay and flow cytometry. We screened the target gene, endothelial PAS domain-containing protein 1 ( EPAS1 ), using bioinformatics analysis and verified it with the dual luciferase reporter gene experiment. The relationship between EPAS1 and miR-152-3p and their roles in paclitaxel resistance of breast cancer were further investigated using RNA interference and transfection techniques. Results: The expression of miR-152-3p in normal breast tissues and cells was markedly higher than that in breast cancer. Overexpression of miR-152-3p decreased the survival rate and increased the apoptosis rate and sensitivity of MCF-7/TAX cells to paclitaxel. We confirmed that EPAS1 is the target of miR-152-3p and is negatively regulated by this miRNA. Moreover, transfection with EPAS1 siRNA enhanced the susceptibility and apoptosis rate of MCF-7/TAX cells to paclitaxel. Co-transfection of miR-152-3p mimics and EPAS1 increased paclitaxel sensitivity and apoptosis induced by the drug. Conclusion: miR-152-3p inhibits the survival of MCF-7/TAX cells and promotes their apoptosis by targeting the expression of EPAS1 , thereby, enhancing the sensitivity of these breast cancer cells to paclitaxel., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Bioethanol production from syngas using acetogenic bacteria has attracted considerable attention in recent years. However, low ethanol yield is the biggest challenge that prevents the commercialization of syngas fermentation into biofuels using microbial catalysts. The present study demonstrated that ethanol metabolism plays an important role in recycling NADH/NAD + during autotrophic growth. Deletion of bifunctional aldehyde/alcohol dehydrogenase ( adhE ) genes leads to significant growth deficiencies in gas fermentation. Using specific fermentation technology in which the gas pressure and pH were constantly controlled at 0.1 MPa and 6.0, respectively, we revealed that ethanol was formed during the exponential phase, closely accompanied by biomass production. Then, ethanol was oxidized to acetate via the aldehyde ferredoxin oxidoreductase pathway in Clostridium ljungdahlii A metabolic experiment using 13 C-labeled ethanol and acetate, redox balance analysis, and comparative transcriptomic analysis demonstrated that ethanol production and reuse shared the metabolic pathway but occurred at different growth phases. IMPORTANCE Ethanol production from carbon monoxide (CO) as a carbon and energy source by Clostridium ljungdahlii and " Clostridium autoethanogenum " is currently being commercialized. During gas fermentation, ethanol synthesis is NADH-dependent. However, ethanol oxidation and its regulatory mechanism remain incompletely understood. Energy metabolism analysis demonstrated that reduced ferredoxin is the sole source of NADH formation by the Rnf-ATPase system, which provides ATP for cell growth during CO fermentation. Therefore, ethanol production is tightly linked to biomass production (ATP production). Clarification of the mechanism of ethanol oxidation and biosynthesis can provide an important reference for generating high-ethanol-yield strains of C. ljungdahlii in the future., (Copyright © 2020 American Society for Microbiology.)

Purpose: To assess the efficacy of diffusion kurtosis imaging (DKI) in the prediction of the treatment response to neoadjuvant chemotherapy in patients with locally advanced gastric cancer (LAGC)., Methods: A total of 31 LAGC patients were enrolled in this prospective study. All patients underwent diffusion-weighted MRI examination (with b = 0 1 , 200 1 , 500 1 , 800 2 , 1000 4 , 1500 4 , 2000 6 s/mm 2 , the subscript denotes the number of signal averages) before and after chemotherapy. DKI and mono-exponential (b = 0, 800 s/mm 2 ) models were built. Apparent diffusion coefficient (ADC), mean diffusivity (MD) and mean kurtosis (MK) of the LAGC tumors were measured. The absolute change values (ΔX) and percentage change values (%ΔX) of the above parameters post neoadjuvant chemotherapy (NACT) were calculated. The response was evaluated according to the pathological tumor regression grade scores (effective response group: TRG 0-2, poor response group: TRG 3). Mann-Whitney U test and receiver operating characteristic (ROC) curves were applicated for statistical analysis., Results: There were 17 patients in the effective response group (ERG), and 14 patients in the poor response group (PRG). The MK pre and MK post values in PRG were significantly higher than those in ERG [(0.671 ± 0.026) and (0.641 ± 0.019) vs. (0.584 ± 0.023) and (0.519 ± 0.018), p < 0.001]. ADC post and MD post in PRG were significantly lower than those in ERG (p = 0.005, p =0.001). Significant differences were also observed for % ΔMK, ΔMD and ΔMK between the two groups (p < 0.05). The area under the curve (AUC) for the prediction of PRG was highest for MK post (AUC = 0.958, cutoff value = 0.614). The MK pre and MK post had the highest sensitivity (91.70 %) and specificity (93.80 %) in the prediction of PRG, respectively., Conclusion: Both DKI and ADC values show potential for the prediction of the PRG in LAGC patients. The DKI parameters, especially MK post displayed the best performance., (Copyright © 2020. Published by Elsevier B.V.)

Purpose: To evaluate the feasibility of arthroscopic reduction percutaneous fixation (ARPF) in the treatment of isolated medial malleolar fracture and compare the results with those of conventional open reduction internal fixation (ORIF)., Methods: This prospective study enrolled 77 patients with isolated medial malleolar fracture between November 2011 and February 2016. The patients were assigned to the ARPF (n = 34) and ORIF (n = 43) groups. The Olerud-Molander ankle score (OMAS), ankle range of motion (ROM), visual analog scale, and radiographic evaluation were determined at the scheduled follow-up., Results: In the ARPF group, 11 of 34 patients (32.4%) had chondral lesions. Tears of the deltoid ligament and anterior inferior tibiofibular ligament were noted in 3 (8.8%) and 15 (44.1%) patients, respectively. The mean follow-up was 5 years. The mean OMAS was higher in the ARPF group than in the ORIF group. The differences were statistically significant at 6 months (mean ± standard deviation, 80.2 ± 4.0 for ARPF vs 77.2 ± 4.1 for ORIF, P = .005) and 1 year (92.9 ± 4.9 vs 88.1 ± 4.6, P < .001), but not at the latest follow-up (P = .081). Ankle ROM was markedly improved in the ARPF group, unlike in the ORIF group at 6 months (dorsiflexion, P = .025; plantarflexion, P < .001) and 1 year (dorsiflexion and plantarflexion, P < .001). The improvement remained at the latest follow-up in plantarflexion (P = .001) but not in dorsiflexion (P = .354)., Conclusions: Arthroscopy-assisted reduction is a feasible alternative modality with superior short-term outcomes for treating isolated medial malleolar fracture, but its superiority may be attenuated in the intermediate term., Level of Evidence: Level III, comparative study., (Copyright © 2020 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Both CO and H 2 can be utilized as energy sources during the autotrophic growth of Clostridium ljungdahlii . In principle, CO is a more energetically and thermodynamically favorable energy source for gas fermentation in comparison to H 2 . Therefore, metabolism may vary during growth under different energy sources. In this study, C. ljungdahlii was fed with CO and/or CO 2 /H 2 at pH 6.0 with a gas pressure of 0.1 MPa. C. ljungdahlii primarily produced acetate in the presence of H 2 as an energy source, but produced alcohols with CO as an energy source under the same fermentation conditions. A key enzyme activity assay, metabolic flux analysis, and comparative transcriptomics were performed for investigating the response mechanism of C. ljungdahlii under different energy sources. A CO dehydrogenase and an aldehyde:ferredoxin oxidoreductase were found to play important roles in CO utilization and alcohol production. Based on these findings, novel metabolic schemes are proposed for C. ljungdahlii growing on CO and/or CO 2 /H 2 . These schemes indicate that more ATP is produced during CO-fermentation than during H 2 -fermentation, leading to increased alcohol production., (Copyright © 2020 Zhu, Liu, Zhou, Yi, Lun, Wang, Tang and Li.)

To explore effects of the sDR5-Fc fusion protein on ulcerative colitis of infant mice via the TRAIL-DR5 pathway, 50 female mice were randomly divided into 5 groups, i.e., control group (group A), dextran sulfate sodium group (group B), hIgG group (group C), 10 mg/kg sDR5-Fc group (group D), and 20 mg/ kg sDR5-Fc group (group E). The acute ulcerative colitis models were established. The weights and disease activity index (DAI) of each group were monitored daily. In addition, the pathological changes of colon tissues were observed by Hematoxylin-Eosin staining. The number of macrophages in colon tissues was detected by immunohistochemistry assay. Changes in the expression of inflammatory factors in colon tissues were detected by quantitative real-time polymerase chain reaction (PCR). Lipopolysaccharide (LPS) of different concentrations was utilized alone or in combination with TRAIL to stimulate the NCM460 cells. The activation of NLRP3 inflammasomes was detected by Western blot. The apoptosis of NCM460 cells was detected by flow cytometry. The results showed that in groups B and C, the body weights decreased, the DAI increased, the colon epithelial cells were injured, the inflammatory cells were infiltrated, and the macrophages in colon tissues increased significantly. In groups D and E, the body weights increased, the DAI decreased, the inflammation was significantly improved, the macrophages decreased significantly, and the gene expression levels of NLRP3, Caspase-1, and IL-1β decreased significantly. Thus, sDR5-Fc could inhibit the activation of NLRP3 inflammasomes induced by TRAIL, thereby decreasing the apoptosis of NCM460 cells. In conclusion, the sDR5-Fc fusion protein could block the TRAIL-DR5 pathway to reduce the expression of NLRP3 inflammasomes, thereby improving ulcerative colitis., (Copyright 2020 Biolife Sas. www.biolifesas.org.)

Background: Trichinella nematodes are globally distributed food-borne pathogens, in which Trichinella spiralis is the most common species in China. Microsatellites are a powerful tool in population genetics and phylogeographic analysis. However, only a few microsatellite markers were reported in T. spiralis. Thus, there is a need to develop and validate genome-wide microsatellite markers for T. spiralis., Methods: Microsatellites were selected from shotgun genomic sequences using MIcroSAtellite identification tool (MISA). The identified markers were validated in 12 isolates of T. spiralis in China., Results: A total of 93,140 microsatellites were identified by MISA from 9267 contigs in T. spiralis genome sequences, in which 16 polymorphic loci were selected for validation by PCR with single larvae from 12 isolates of T. spiralis in China. There were 7-19 alleles per locus (average 11.25 alleles per locus). The observed heterozygosity (H O ) and expected heterozygosity (H E ) ranged from 0.325 to 0.750 and 0.737 to 0.918, respectively. The polymorphism information content (PIC) ranged from 0.719 to 0.978 (average 0.826). Among the 16 loci, markers for 10 loci could be amplified from all 12 international standard strains of Trichinella spp., Conclusions: Sixteen highly polymorphic markers were selected and validated for T. spiralis. Primary phylogenetic analysis showed that these markers might serve as a useful tool for genetic studies of Trichinella parasites.

Selecting an ideal molecular format from diverse structures is a major challenge in developing a bispecific antibody (BsAb). To choose an ideal format of anti-CD3 × anti-transferrin receptor (TfR) bispecific antibodies for clinical application, we constructed TfR bispecific T-cell engager (BiTE) in two extensively applied formats, including single-chain tandem single-chain variable fragments (scFvs) and double-chain diabodies, and evaluated their functional characterizations in vitro. Results demonstrated that TfR-BiTE in both formats directed potent killing of TfR + HepG2 cells. However, compared to two-chain diabodies, scFvs were more efficient in antigen binding and TfR + target killing. Furthermore, different domain orders in scFvs would also be evaluated because single-TfR-CD3-His was preferable to single-CD3-TfR-His in immunotherapeutic strategies. Thus, the single-chain tandem TfR-CD3 format was favored for further investigation in cancer therapy.

Background: Cardiovascular disease is the leading cause of death worldwide. Tissue repair after pathological injury in the heart remains a major challenge due to the limited regenerative ability of cardiomyocytes in adults. Stem cell-derived cardiomyocytes provide a promising source for the cell transplantation-based treatment of injured hearts., Aim: To explore the function and mechanisms of miR-301a in regulating cardiomyocyte differentiation of mouse embryonic stem (mES) cells, and provide experimental evidence for applying miR-301a to the cardiomyocyte differentiation induction from stem cells., Methods: mES cells with or without overexpression of miR-301a were applied for all functional assays. The hanging drop technique was applied to form embryoid bodies from mES cells. Cardiac markers including GATA-4, TBX5, MEF2C, and α-actinin were used to determine cardiomyocyte differentiation from mES cells., Results: High expression of miR-301a was detected in the heart from late embryonic to neonatal mice. Overexpression of miR-301a in mES cells significantly induced the expression of cardiac transcription factors, thereby promoting cardiomyocyte differentiation and beating cardiomyocyte clone formation. PTEN is a target gene of miR-301a in cardiomyocytes. PTEN-regulated PI3K-AKT-mTOR-Stat3 signaling showed involvement in regulating miR-301a-promoted cardiomyocyte differentiation from mES cells., Conclusion: MiR-301a is capable of promoting embryonic stem cell differentiation to cardiomyocytes., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest associated with this manuscript., (©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.)

Mitochondrial genomes are widely used for phylogenetic and phylogeographic analyses among arthropods, but there is a lack of sufficient mitochondrial genome sequence data for spiders. Herein, we sequenced and characterized the complete mitochondrial genome of a crab spider Ebrechtella tricuspidata (Araneae: Thomisidae). The circular mitochondrial genome is 14,352 bp long, including a standard set of 37 genes and an A + T-rich region. Nucleotide composition is highly biased toward A + T nucleotides (77.3%). A novel gene order rearrangement is detected by a tRNA (trnL1) translocation. Tandem repeats are not identified in the A + T-rich region. Most of the tRNAs are greatly reduced in size and cannot be folded into typical cloverleaf-shaped secondary structures. The phylogenetic analysis confirms that the mitochondrial genome sequences are useful in resolving higher-level relationship of Araneae. Overall, our data present in this study will elevate our knowledge on the architecture and evolution of spider mitochondrial genome., (Copyright © 2018 Elsevier Inc. All rights reserved.)

MiRNAs are integral for maintaining immune homeostasis and self-tolerance. In this study, qPCR analyses were performed to determine which miRNAs play an important role in wound healing. Next, an experiment in a model of wound healing was performed, and histology, mRNA expression and T-cell subpopulations in wound tissue were analyzed. The accelerated experiments were performed by local injection of either rIL-17A and/or rIL-9 after wound healing. In vitro, the differentiation of Th17/Th9 in miR-155 +/+ or miR-155 -/- mice was investigated, and the target genes of miR155 were analyzed. From our findings, miR-155 -/- in mice promoted wound healing and weakened T cell-mediated inflammation, especially in IL-17/IL-9, and less severe skin fibrosis developed in the mice. rIL-17A and/or rIL-9 could exacerbate inflammatory injury and delay wound healing. We also demonstrated that miR-155 -/- led to a defect in the differentiation of Th17/Th9 in vitro, and this effect of IL-17/IL-9 might be related to the expression of C-maf, which is a target gene of miR155. MiR-155 regulated IL-17/IL-9-related inflammation in wound healing and might be a potential therapeutic target to attenuate the inflammatory response in wound tissue and promote the closure of wound injuries.

The reduction of nuclear fast red (NFR) stain by sodium tetrahydroboron was catalyzed in the presence of silver ions (Ag + ). The fluorescence properties of reduced NFR differed from that of NFR. The product showed fluorescence emission at 480 nm with excitation at 369 nm. Furthermore, the fluorescence intensity of the mixture increased strongly in the presence of Ag + and Britton-Robinson buffer at pH 4.78. There was a good linear relationship between increased fluorescence intensity (ΔI) and Ag + concentration in the range 5.0 × 10 -9 to 5.0 × 10 -8  M. The correlation coefficient was 0.998, and the detection limit (3σ/k) was 1.5 × 10 -9  M. The colour of the reaction system changed with variation in Ag + concentration over a wide range. Based on the colour change, a visual semiquantitative detection method for recognition and sensing of Ag + was developed for the range 1.0 × 10 -8  to 5.0 × 10 -4  M, with an indicator that was visible to the naked eye. Therefore, a sensitive, simple method for determination of Ag + was developed. Optimum conditions for Ag + detection, the effect of other ions and the analytical application of Ag + detection of synthesized sample were investigated., (© 2019 John Wiley & Sons, Ltd.)

Jinze Reservoir is the main drinking water source for southwest Shanghai. The water quality in the upstream Taipu River and reservoir have an important impact on the performance of the reservoir and the quality of the water supply. Conventional water parameters were analyzed using principal component analysis (PCA) to evaluate seasonal variations in water quality in the upper reaches of Jinze Reservoir. The parallel factor (PARAFAC) was also used to analyze water-soluble dissolved organic matter (FDOM) in the upstream waters and reservoir area. Furthermore, the relationships between water fluorescence intensity and conventional water quality indicators were analyzed using correlation analysis. The results show that water quality in the upper reaches of Jinze Reservoir is worst in the winter, and water quality gradually deteriorates in the outer sections of the reservoir due to external pollution inputs. Ecological purification within the reservoir area functions to improve water quality. The water body FDOM content is mainly composed of proteinoids and humus. Protein-like substances are the main components of this material, and each component exhibits clear spatial and temporal distribution characteristics. External pollution is the main factor affecting the total fluorescence intensity of the FDOM outside of the reservoir. In the reservoir, the ecological environment affects the total fluorescence intensity of FDOM. The total fluorescence intensity of FDOM showed an increasing downstream spatial trend, which was significantly correlated with NH 4 + -N, petroleum, TOC, chloride, and sulfate content in the water. By detecting the total fluorescence intensity of FDOM, the rapid analysis of water quality can be achieved to inform early warning.