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The aim of the present study was to assess the effect of remifentanil on the incidence of emergence agitation in preschool-aged children undergoing adenotonsillectomy with sevoflurane anaesthesia. Sixty children, aged three to seven years, American Society of Anesthesiologists physical status I or II, were randomised into either group S (sevoflurane alone, n=30) or group R (sevoflurane plus remifentanil, n=30). Anaesthesia was induced with an intravenous bolus injection of fentanyl 3 microg/kg and propofol 2.5 mg/kg. Endotracheal intubation was facilitated by vecuronium 0.1 mg/kg. All patients were ventilated with 50% nitrous oxide and 1.5 to 2.5% sevoflurane in oxygen. End-tidal CO2 was maintained at 35 +/- 4 mmHg. Group S received no other medication while group R received remifentanil 1 microg/kg/minute intraoperatively. Mean blood pressure, heart rate, pulse oximetry, eye-opening time and extubation time were recorded in the operating room. In recovery, emergence agitation was assessed using the Pediatric Anesthesia Emergence Delirium scale with a score > or =10 taken as indicating agitation. Emergence agitation occurred in 20 of the 30 patients in group S and seven of the 30 patients in group R (P < 0.01). In preschool-aged children undergoing adenotonsillectomy with sevoflurane general anaesthesia, after propofol and fentanyl induction, intraoperative remifentanil decreased the incidence of emergence agitation. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Huntington disease (HD), and Multiple sclerosis (MS), pose a significant global health challenge due to their intricate pathology and limited therapeutic interventions. Natural products represent invaluable reservoirs for combating these neurodegenerative diseases by targeting key pathological hallmarks such as protein aggregation, synaptic dysfunction, aberrant proteostasis, cytoskeletal abnormalities, altered energy homeostasis, inflammation, and neuronal cell death. This review provides an in-depth analysis of the mechanisms and therapeutic targets of natural products for their neuroprotective effects. Furthermore, it elucidates the current progress of clinical trials investigating the potential of natural products in delaying neurodegeneration. The objective of this review is to enhance the comprehension of natural products in the prevention and treatment of neurodegenerative diseases, offering new insights and potential avenues for future pharmaceutical research., Competing Interests: Declaration of competing interest All of the authors declared there are no conflicts of interest for this manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The current method for liver graft implantation during the anhepatic phase is complex. Therefore, this study aimed to introduce a modified orthotopic liver transplantation (OLT) technique with major vascular reconstruction using cuff technique to simplify the process of liver graft implantation during the anhepatic phase., Methods: Twenty-four canines were randomly assigned to two groups: the modified orthotopic liver transplantation group (M-OLT, n  = 12) and the control group (n = 12). All animals were randomly assigned to the donor or recipient groups. The recipients received orthotopic liver transplantation using a modified technique in the M-OLT group, and OLT using traditional implantation technique without venovenous bypass was performed in the control group. The donor and recipient characteristics were compared between the two groups. Vascular anastomotic patency was evaluated using angiography immediately and one week after surgery., Results: All recipients underwent successful liver transplantation. There were no significant differences between the two groups in terms of sex, body weight, or cold ischemia time of the donor liver. However, recipients in the M-OLT group had a shorter operation time, less intraoperative blood loss, shorter anhepatic phase, shorter vascular occlusion time, and shorter warm ischemia time than that in the control group (all p  < 0.05). No anastomotic leakage or stenosis was detected in either group after liver transplantation. One recipient in the M-OLT group and three in the control group died within one week of transplantation., Conclusions: This modified technique is safe and feasible for canine liver transplantation and can significantly simplify liver graft implantation procedures during the anhepatic period., Competing Interests: No authors have conflicts of interest or financial ties to disclose., (© 2024 The Authors. Published by Elsevier Inc.)

Translational pharmacological research on traditional medicines lays the foundation for precisely understanding how the medicines function in the body to deliver therapeutic benefits. Borneolum syntheticum (Bingpian) is commonly used in Chinese herbal medicines for coronary heart disease, but its specific cardiovascular impact remains poorly understood. Isoborneol, a constituent of Bingpian, has been found to reduce lipid accumulation in macrophages in vitro, but its oral bioavailability is limited. This investigation aimed to evaluate anti-atherosclerotic effects of Bingpian, based on understanding its first-pass metabolism. Human subjects orally received an herbal medicine containing Bingpian and their plasma samples were analyzed to identify the major circulating compounds of Bingpian, with the metabolism that was also characterized in vitro and in mice. The identified compounds were evaluated for their ability to inhibit macrophage foam-cell formation induced by oxidized low-density lipoprotein. Furthermore, the anti-atherosclerotic effect of repeatedly dosed Bingpian was assessed in ApoE -/- mice fed a high-fat diet. In human subjects, the major circulating compounds of Bingpian were metabolites, rather than their precursor constituents borneol and isoborneol. These constituents were efficiently absorbed in the intestinal tract but underwent significant first-pass metabolism, involving UGT2B7-mediated glucuronidation into borneol-2-O-glucuronide and isoborneol-2-O-glucuronide, respectively, and CYP2A6/2B6/3A-mediated oxidation both into camphor. Despite their poor membrane permeability, hepatic efflux of borneol-2-O-glucuronide and isoborneol-2-O-glucuronide into the systemic circulation was enhanced by MRP3/4. The circulating metabolites, particularly their combinations, markedly inhibited macrophage foam-cell formation induced by oxidized low-density lipoprotein in vitro. Sub-chronic administration of Bingpian (30 mg·kg -1 ·d - 1 , i.g.) for 12 weeks significantly decreased atherosclerotic lesion size and enhanced plaque stability in ApoE -/- mice. Systemic exposure to Bingpian metabolites in mice closely resembles that in humans, suggesting that the pharmacodynamic effects of Bingpian in mice are likely applicable to humans. Overall, the cardiovascular benefits of Bingpian involve reducing atherosclerosis by inhibiting foam-cell formation through its metabolites. This investigation supports that oral Bingpian could be a druggable agent for reducing atherosclerosis., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Background: Despite the growing research on 3D printing (3DP) in cardio-thoracic diseases, comprehensive bibliometric analyses remain scarce. This study aims to bridge this gap by identifying key research trends and hotspots within the field., Methods: A bibliometric analysis was conducted on publications from 1991 to 2024 using data from the Web of Science Core Collection, with analysis performed using VOSviewer, CiteSpace, and the R package 'bibliometrix'., Results: The analysis included 2,836 documents authored by 14,206 researchers across 85 countries. A significant rise in annual publications was observed, with the United States, China, and the United Kingdom leading in contributions. Prominent institutions, including Stanford University, were highlighted, while Scientific Reports and Biomaterials were identified as influential journals. Key research areas encompass cardiovascular, lung, and breast diseases, along with chest wall reconstructions, with emerging trends focusing on advanced materials for drug delivery and tissue engineering., Conclusion: This comprehensive bibliometric analysis of 3DP in cardio-thoracic diseases reveals global research trends, emerging themes, and the crucial role of 3DP in advancing medical education and personalized treatment, highlighting areas for future research and development., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Ethnopharmacological Relevance: Bu-Zhong-Yi-Qi Decoction(BZYQD) is a traditional formula commonly used in China, known for its effects in tonifying Qi and raising Yang. It can relieve symptoms of cognitive impairment such as forgetfulness and lack of concentration caused by qi deficiency, which is common in aging and debilitating. However, much of the current research on BZYQD has been focused on its impact on the digestive system, leaving its molecular mechanisms in improving cognitive function largely unexplored., Aim of the Study: Cognitive decline in the aging central nervous system is intrinsically linked to oxidative damage. This study aims to investigate the therapeutic mechanism of BZYQD in treating mild cognitive impairment caused by qi deficiency, particularly through repair of mitochondrial oxidative damage., Materials and Methods: A rat model of mild cognitive impairment (MCI) was established by administering reserpine subcutaneously for two weeks, followed by a two-week treatment with BZYQD/GBE. In vitro experiments were conducted to assess the effects of BZYQD on neuronal cells using a H 2 O 2 -induced oxidative damage model in PC12 cells. The open field test and the Morris water maze test evaluated the cognitive and learning memory abilities of the rats. HE staining and TEM were employed to observe morphological changes in the hippocampus and its mitochondria. Mitochondrial activity, ATP levels, and cellular viability were measured using assay kits. Protein expression in the SIRT3/MnSOD/OGG1 pathway was analyzed in tissues and cells through western blotting. Levels of 8-OH-dG in mitochondria extracted from tissues and cells were quantified using ELISA. Mitochondrial morphology in PC12 cells was visualized using Mito Red, and mitochondrial membrane potential was assessed using the JC-1 kit., Results: BZYQD treatment significantly improved cognitive decline caused by reserpine in rats, as well as enhanced mitochondrial morphology and function in the hippocampus. Our findings indicate that BZYQD mitigates mtDNA oxidative damage in rats by modulating the SIRT3/MnSOD/OGG1 pathway. In PC12 cells, BZYQD reduced oxidative damage to mitochondria and mtDNA in H 2 O 2 -induced conditions and was associated with changes in the SIRT3/MnSOD/OGG1 pathway., Conclusion: BZYQD effectively counteracts reserpine-induced mild cognitive impairment and ameliorates mitochondrial oxidative stress damage through the SIRT3/MnSOD/OGG1 pathway., 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 Elsevier B.V. All rights reserved.)

Sepsis is a severe systemic infectious disease that often leads to multi-organ dysfunction. One of the common and serious complications of sepsis is renal injury. In this study, we aimed to investigate the potential mechanistic role of a novel compound called H-151 in septic kidney injury. We also examined its impact on renal function and mouse survival rates. Initially, we confirmed abnormal activation of the STING-TBK1 signaling pathway in the kidneys of septic mice. Subsequently, we treated the mice with H-151 and observed significant improvement in sepsis-induced renal dysfunction. This was evidenced by reductions in blood creatinine and urea nitrogen levels, as well as a marked decrease in inflammatory cytokine levels. Furthermore, H-151 substantially improved the seven-day survival rate of septic mice, indicating its therapeutic potential. Importantly, H-151 also exhibited an inhibitory effect on renal apoptosis levels, further highlighting its mechanism of protecting against septic kidney injury. These study findings not only offer new insights into the treatment of septic renal injury but also provide crucial clues for further investigations into the regulatory mechanisms of the STING-TBK1 signaling pathway and potential drug targets.

Fusarium head blight is a devastating disease that causes severe yield loses and mycotoxin contamination in wheat grain. Additionally, balancing the trade-off between wheat production and disease resistance has proved challenging. This study aimed to expand the genetic tools of the endophyte Phomopsis liquidambaris against Fusarium graminearum. Specifically, we engineered a UDP-glucosyltransferase-expressing P. liquidambaris strain (PL-UGT) using ADE1 as a selection marker and obtained a deletion mutant using an inducible promoter that drives Cas9 expression. Our PL-UGT strain converted deoxynivalenol (DON) into DON-3-G in vitro at a rate of 71.4 % after 36 h. DON inactivation can be used to confer tolerance in planta. Wheat seedlings inoculated with endophytic strain PL-UGT showed improved growth compared with those inoculated with wildtype P. liquidambaris. Strain PL-UGT inhibited the growth of Fusarium graminearum and reduced infection rate to 15.7 %. Consistent with this finding, DON levels in wheat grains decreased from 14.25 to 0.56 μg/g when the flowers were pre-inoculated with PL-UGT and then infected with F. graminearum. The expression of UGT in P. liquidambaris was nontoxic and did not inhibit plant growth. Endophytes do not enter the seeds nor induce plant disease, thereby representing a novel approach to fungal disease control., 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 Inc.)

Background: Research studies on Asian women's preferences for breast augmentation and the factors that influence decision-making are scarce or unrepresentative., Methods: This study was conducted from September 2016 to September 2017, a period of one year. We developed a questionnaire for Chinese female with breast augmentation intentions based on the Breast-Q questionnaire, the world's most popular breast augmentation assessment tool, and conducted questionnaire surveys in 35 hospitals located in 19 provinces in mainland China among female who came to hospitals to inquire about breast augmentation surgery., Results: A total of 2066 questionnaires were collected from female interested in breast augmentation. The age range at the time of response was 19-53 years (mean 31.2 ± 6.8 years). More than half of the respondents (58.1%) were married, and 70.4% of them had children. The respondents rated their dressed image significantly higher than their nude image. Their partners also rated their breast image poorly, with 43% rating it fair and 30.4% negatively. Internal reasons, such as improving self-confidence and creating a better body image, were the main motivators for breast augmentation. More than half of the respondents had only limited understanding of breast augmentation surgery or had heard of it but did not fully understand it (33.2% and 27.5%, respectively), and 69.4% had considered breast augmentation for less than three years. A total of 49.2% of the respondents learned about breast augmentation surgery through the Internet. A total of 43.8% of the respondents did not receive support from family members or partners. Surgical safety (20.4%), surgical effect (17.1%), and surgeon's skill (16.6%) were given the highest priority. The surgeon's professionalism, popularity, and academic background were also high on people's list of considerations., Conclusions: The results of our breast augmentation survey provide data on many Chinese women considering breast augmentation. This will help plastic surgeons better understand the characteristics, preferences, and concerns of Chinese women undergoing breast augmentation and will be used to guide patient-doctor communication and help Chinese women make the most informed decisions., Level of Evidence V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

The isatin group is widespread in nature and is considered to be a privileged building block for drug discovery. In order to develop novel SHP1 inhibitors with fluorescent properties as tools for SHP1 biology research, this work designed and synthesized a series of isatin derivatives. The presentive compound 5a showed good inhibitory activity against SHP1 PTP with IC 50 of 11 ± 3 μM, displayed about 92% inhibitory rate against MV-4-11 cell proliferation at the concentration of 20 μM, exhibited suitable fluorescent properties with a long emission wavelength and a large Stokes shift, and presented blue fluorescent imaging in HeLa cells with low cytotoxicity. This study could offer chemical tool to further understand SHP1 biology and develop novel SHP1 inhibitors in therapy.

Background:  Infraorbital filler injection is a commonly used minimally invasive cosmetic procedure on the face, which can cause vascular complications., Objective:  In this study, we aimed to explore the anatomical structure of the infraorbital vasculature and to establish an accurate protocol for infraorbital filler injection., Methods:  The vascular structure of the infraorbital region was evaluated in 84 hemifacial specimens using computed tomography. Four segments (P1-P4) and five sections (C1-C5) were considered. We recorded the number of identified arteries in each slice and at each location and the number of deep arteries. Furthermore, we also measured the infraorbital artery (IOA) distribution., Results:  At P1-P4, the lowest number of arteries was detected in segment P4, with a 317/1727 (18.4%) and 65/338 (2.3%) probability of total and deep arterial identification, respectively. The probabilities of encountering an identified artery at the five designated locations (C1-C5) were 277/1727 (16%), 318/1727 (18.4%), 410/1727 (23.7%), 397/1727 (23%), and 325/1727 (18.8%), respectively. The probability of an IOA being identified at C2 was 68/84 (81%)., Conclusion:  We described an effective filler injection technique in the infraorbital region to minimize the associated risks., Level of Evidence Iv: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

The unpredictable survival rate of autologous fat grafting (AFG) seriously affects its clinical application. Improving the survival rate of AFG has become an unresolved issue in plastic surgery. Peroxisome proliferator-activated receptor-γ (PPAR-γ) regulates the adipogenic differentiation of adipocytes, but the functional mechanism in AFG remains unclear. In this study, we established an animal model of AFG and demonstrated the superior therapeutic effect of PPAR-γ regulation in the process of AFG. From day 3 after fat grafting, the PPAR-γ agonist rosiglitazone group consistently showed better adipose integrity, fewer oil cysts, and fibrosis. Massive macrophage infiltration was observed after 7 days. At the same time, M2 macrophages begin to appear. At day 14, M2 macrophages gradually became the dominant cell population, which suppressed inflammation and promoted revascularization and fat regeneration. In addition, transcriptome sequencing showed that the differentially expressed genes in the Rosiglitazone group were associated with the pathways of adipose regeneration, differentiation, and angiogenesis; these results provide new ideas for clinical treatment., (© 2024 Federation of American Societies for Experimental Biology.)

Orientation regulation of nanoparticles in a suspension by an electric field is a powerful tool to tune its mechanical, thermal, optical, electrical properties etc. However, how molecular modification can affect the orientation of two-dimensional nanoparticles is still unclear. In this paper, the influence of molecular modification on the orientation of graphene nanosheets (GNS) in water was investigated through theoretical analyses and molecular dynamics (MD) simulations. Firstly, a new orientation angle model was proposed, which considers hydration effects, dipole moments and resistance torque. Then, MD simulations were conducted to investigate the effects of position, direction, type, and number of functional groups on the orientation of GNS. The trend observed in MD simulations is consistent with the proposed theoretical model. The results reveal that, under the combined influence of the dipole moment and hydration effects, the modification with hydrophilic functional groups can reduce the orientation angle from 21.31° to 8.34°, while the modification with hydrophobic functional groups increases it to 26.43°. Among the hydrophilic functional groups, orientation of hydroxylated GNS is the best. With an increase in the number of hydroxyl groups, orientation angle is decreased from 12.61° to 8.34°. This work can provide valuable guidance for the design of high-performance suspensions and composites, such as thermal smart materials with adjustable thermal conductivity and intelligent devices with tailored capabilities., (© 2024 IOP Publishing Ltd.)

Objective: To explore clinical efficacy of proximal femoral nail anti-rotation(PFNA),InterTan and proximal femoral bionic intramedullary nail (PFBN) in treating femoral intertrochanteric fracture., Methods: Clinical data of 120 patients with intertrochanteric fracture who were underwent closed reduction intramedullary nail-internal fixation from January 2020 to January 2021 were retrospectively analyzed. According to methods of internal fixation,patients were divided into 3 groups. There were 25 patients in PFBN group,including 16 females and 9 males,aged from 69 to 79 years old with an average of (73.67±5.16) years old. There were 55 patients in PFNA group,including 38 females and 17 males,aged from 68 to 80 years old with an average of (74.23±5.57) years old. There were 40 patients in InterTan group,including 26 females and 14 males,aged from 68 to 79 years old with an average of (73.45±5.34) years old. Operative time,intraoperative blood loss,incision length,hospital stay,weight-bearing time,fracture healing time and complications among 3 groups were compared,and clinical effect was evaluated by Harris score of hip function before operation,1,6 and 12 months after opertaion,respectively., Results: Patients among 3 groups were successfully completed operation and were followed up for more than 12 months. There were no significant difference in hospital stay,operative time,intraoperative blood loss and incision length among 3 groups ( P >0.05). Weight bearing time of PFBN group (7.98±1.34) d and InterTan group (8.22±0.46) d were earlier than that of PFNA group (10.27±0.66) d( P <0.01). Fracture healing time of PFBN group (10.14±2.33) weeks and InterTan group (11.87±2.48) weeks were earlier than that of PFNA group (13.68±2.36) weeks ( P <0.01). One month after operation,Harris score in PFBN group (70.52±5.34) and InterTan group (69.81±6.17) was higher than that of PFNA group (51.46±5.36),and there was no significant difference between PFBN group and InterTan group ( P >0.05). There were no significant difference in Harris scores among 3 groups before operation,6 and 12 months after opertaion( P >0.05). Cases of complication of InterTan group and PFNA group were lower than that of PFNA group ( P <0.05)., Conclusion: PFBN and InterTan for the treatment of intertrochanteric fracture have advantages of faster fracture healing,earlier weight-bearing time and fewer postoperative complications than traditional PFNA,but three operations could achieve higher effective rates without significant difference in long-term results.

Herein, we report the phosphonylacylation of alkenes via visible-light-induced N-heterocyclic carbene (NHC) catalysis to afford a series of γ-ketophosphonates in moderate to good yields. This protocol features mild conditions, free of photocatalyst, and good compatibility of functional groups. The excited Breslow enolate intermediate was proposed to undergo single-electron transfer with oxime phosphonate to generate the corresponding ketyl radical and phosphonyl radical.

Extracts are important intermediates in the production of traditional Chinese medicines preparations. The drying effect of extracts will directly affect the subsequent production process and the quality of the preparation. To meet the requirements of high drug loading, short time consumption, and simple production process of personalized traditional Chinese medicine preparations, this study explored the application of multi-program microwave vacuum drying process in the extract drying of personalized traditional Chinese medicine preparations. The influencing factors of microwave vacuum drying process were investigated for 5 excipients and 40 prescriptions. Taking the feasibility of drying, drying rate, drying time, and dried extract status as indicators, this study investigated the feeding requirements of microwave vacuum drying. With the dried extract status as the evaluation indicator, the three drying programs(A, B, and C) were compared to obtain the optimal drying condition. The experimental results showed that the optimal feeding conditions for microwave vacuum drying were material layer thickness of 2 cm and C program(a total of 7 drying processes), which solved the problem of easy scorching in microwave drying with process management. Furthermore, the preset moisture content of the dried extract in microwave drying should be 4%-5%, so that the dried extract of traditional Chinese medicine preparation had uniform quality, complete drying, and no scorching. This study lays a foundation for the application of microwave drying in the production of traditional Chinese medicine preparations, promoting the high-quality development of personalized traditional Chinese medicine preparations.

A self-chaotic circular-sided square microcavity laser, with a chaos bandwidth of 12.9 GHz and a flatness of ±3 d B , was applied in optical time domain reflectometry (OTDR). Using the broadband chaos laser, we demonstrated a range resolution of 4.5 mm and a 25-km detection distance experimentally. The solitary wide-bandwidth microcavity chaos laser, without the extra correlation peaks in optical feedback chaotic lasers, has shown potential advantages for correlation OTDR in practical application.

Objective: To investigate predictors of anticoagulation efficacy in deep venous thrombosis (DVT) by ultrasound elastography (UE)., Methods: The basic clinical, laboratory and ultrasound treatment data of fifty-eight patients with DVT were collected and analyzed. Then the results of ultrasound after 3-month anticoagulation treatment were compared among different groups. Multiple logistic regression analysis was used to identify independent risk factors that affected anticoagulation efficacy. The predictive efficacy of each independent risk factor was accessed by drawing operating characteristic (ROC) curves., Results: According to the regression analysis, the elastic modulus (OR = 0.631, P = 0.001) and strain rate ratio (OR = 0.332, P = 0.006) were identified as independent risk factors for the effectiveness of anticoagulation therapy in patients with DVT. According to the ROC curves, elastic modulus and strain rate ratio could predict effective anticoagulation therapy for DVT, and the optimal threshold values were 22.10 kPa and 1.80 respectively. The corresponding AUC values were 0.879 and 0.854, with a sensitivity of 71.4% and 59.5%, a specificity of 93.7%, and a Youden index of 65.1% and 62.7%, respectively., Conclusions: The elastic modulus (≤22.10 kPa) or strain rate ratio (≤1.80) of the thrombus were independent predictors for the effectiveness of anticoagulation therapy.

Insensitivity to external optical feedback is experimentally demonstrated in a self-chaotic deformed square microcavity laser for the first time, to the best of our knowledge. Both the optical and radio frequency (RF) spectra of the microlaser remain unaffected for external optical feedback with feedback strength as high as 9.9 dB. In addition, the autocorrelation function curve exhibits no time-delayed peaks. The insensitivity makes the self-chaotic microcavity laser promising for applications in feedback-insensitive optical sources.

Objective: This study aimed to explore the roles of duration and burden of atrial high-rate episode (AHRE) on ischemic stroke in patients with pacemaker implantation., Methods: Patients with pacemaker implantation for bradycardia from 2013 to 2017 were consecutively enrolled. Data such as gender, age, combined diseases, type of AF, left atrial size, left ventricular size, left ventricular ejection fraction, CHA 2 DS 2 -VASc score, and anticoagulants were collected. The burden and duration of AHRE based on different interval partition were also recorded in detail to evaluate the impacts on ischemic stroke. Cox regression analysis with time-dependent covariates was conducted., Results: A total of 220 patients with AHRE were enrolled. The average follow-up time was 48.42 ± 17.20 months. Univariate regression analysis showed that diabetes (p = .024), high CHA 2 DS 2 -VASc score (≥ 2) (p = .021), long mean AHRE burden (p = .011), long maximal AHRE burden (p = .015), long AHRE duration lasting≥48 h (p = .001) or 24 h (p = .001) or 12 h (p = .005) were prone to ischemic stroke. Further multivariate regression analysis showed that long duration of AHRE (≥48 h) (HR 10.77; 95% CI 3.22-55.12; p = .030) were significantly correlated with stroke in patients with paroxysmal AF. There was no significant correlation between the type of AF and stroke (p = .927)., Conclusion: The longer duration of AHRE (≥48 h) was more favorable in predicting ischemic stroke than high CHA 2 DS 2 -VASc score (≥2)., (© 2023 The Authors. Pacing and Clinical Electrophysiology published by Wiley Periodicals LLC.)

The dysregulation of the phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin signaling pathway has been implicated in various human cancers, and isoform-selective inhibitors targeting PI3Kα have received significant interest in recent years. In this study, we have designed and synthesized three series of substituted benzoxazole derivatives based on the clinical candidate TAK-117 (8a). A detailed structure-activity relationship (SAR) study has identified the optimal compound 18a bearing a quinoxaline scaffold. Compared to the control 8a, 18a exhibited 4.4-fold more potent inhibitory activity against PI3Kα (IC 50 : 2.5 vs 11 nM) and better isoform-selective profiles over other PI3Ks. In addition, 18a showed a 1.5-fold more potent antiproliferative effect against HCT-116 cell lines (IC 50 : 3.79 vs 5.80 μM) and a better selectivity over the normal tissue cells. The potential antitumor mechanism and in vitro metabolic stability of 18a were also investigated. Notably, pharmacokinetic assays indicated that 18a had a higher plasma exposure, a higher maximum concentration and shorter elimination time compared to 8a., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

The abnormal activation of the mTOR pathway is closely related to the occurrence and progression of cancer, especially colorectal cancer. In this study, a rational virtual screening strategy has been established and MT-5, a novel mTOR inhibitor with a quinoline scaffold, was obtained from the ChemDiv database. MT-5 showed potent kinase inhibitory activity (IC 50 : 8.90 μM) and antiproliferative effects against various cancer cell lines, especially HCT-116 cells (IC 50 : 4.61 μM), and this was 2.2-fold more potent than that of the cisplatin control (IC 50 : 9.99 μM). Western blot, cell migration, cycle arrest, and apoptosis assays were performed with HCT-116 cells to investigate the potential anticancer mechanism of MT-5. Metabolic stability results in vitro indicated that MT-5 exhibited good stability profiles in artificial gastrointestinal fluids, rat plasma, and liver microsomes. In addition, the key contribution of the residues around the binding pocket of MT-5 in binding to the mTOR protein was also investigated from a computational perspective., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To identify the predictors of pacing-induced cardiomyopathy (PICM) and illustrate the safety and feasibility of conduction system pacing (CSP) upgrade on patients with long-term persistent atrial fibrillation (AF)., Methods: All patients with long-term persistent AF and normal left ventricular ejection fraction (LVEF) ≥50% were consecutively enrolled from January 2008 to December 2017, and all the patients with atrioventricular block (AVB) and high right ventricular pacing (RVP) percentage of at least 40%. The predictors of PICM were identified, and patients with PICM were followed up for at least 1 year regardless of CSP upgrade. Cardiac performances and lead outcomes were investigated in all patients before and after CSP upgrade., Results: The present study included 139 patients, out of which 37 (26.62%) developed PICM, resulting in a significant decrease in the left ventricular ejection fraction (LVEF) from 56.11 ± 2.56% to 38.10 ± 5.81% (p< .01). The median duration for the development of PICM was 5.43 years. Lower LVEF (≤52.50%), longer paced QRS duration (≥175 ms), and higher RVP percentage (≥96.80%) were identified as independent predictors of PICM. Furthermore, the morbidity of PICM progressively increased with an increased number of predictors. The paced QRS duration (183.90 ± 22.34 ms vs. 136.57 ± 20.71 ms, p < .01), LVEF (39.35 ± 2.71% vs. 47.50 ± 7.43%, p < .01), and left ventricular end-diastolic diameter (LVEDD) (55.53 ± 5.67 mm vs. 53.20 ± 5.78 mm, p = .03) improved significantly on patients accepting CSP upgrade. CSP responses and complete reverse remodeling (LVEF ≥50% and LVEDD < 50 mm) were detected in 80.95% (17/21) and 42.9% (9/21) of patients. The pacing threshold (1.52 ± 0.78 V/0.4 ms vs. 1.27 ± 0.59 V/0.4 ms, p = .16) was stable after follow-up., Conclusion: PICM is very common in patients with long-term persistent AF, and CSP upgrade was favorable for better cardiac performance in this patient population., (© 2023 Wiley Periodicals LLC.)

Main Conclusion: Arabidopsis GR1 and NTRA function in pollen tube penetrating the stigma into the transmitting tract during pollination. During pollination, recognition between pollen (tube) and stigma mediates the hydration and germination of pollen, as well as the growth of the pollen tube on the stigma. Arabidopsis glutathione reductase 1 (GR1) and NADPH-dependent thioredoxin reductase A (NTRA) are involved in regulating cell redox hemostasis. Both GR1 and NTRA are expressed in pollen, but their roles in pollen germination and the growth of the pollen tube need further investigation. In this study, we performed pollination experiments and found that the Arabidopsis gr1/ + ntra/- and gr1/- ntra/ + double mutation compromised the transmission of male gametophytes. Pollen morphology and viability of the mutants did not show obvious abnormalities. Additionally, the pollen hydration and germination of the double mutants on solid pollen germination medium were comparable to those of the wild type. However, the pollen tubes with gr1 ntra double mutation were unable to penetrate the stigma and enter the transmitting tract when they grew on the surface of the stigma. Our results indicate that GR1 and NTRA play a role in regulating the interaction between the pollen tube and the stigma during pollination., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The relationship between cumulative non-high-density lipoprotein cholesterol (non-HDL-C) burden and atherosclerotic cardiovascular disease (ASCVD) remains unclear., Objective: To prospectively examine the association between cumulative non-HDL-C burden and ASCVD risk in the Kailuan cohort of China., Methods: A total of 49,679 subjects who were free of ASCVD participated in three consecutive examinations in 2006, 2008 and 2010 were enrolled. Duration and concentration of cumulative exposure to non-HDL-C (cumNon-HDL-C) were respectively used to estimate the extent of cumulative non-HDL-C burden. The participants were divided into four groups according to durations of cumNon-HDL-C (0, 2, 4 and 6 years) and five groups according to the quintiles of cumNon-HDL-C concentration (<10.93, 10.93-12.68, 12.69-14.32, 14.33-16.72 and ≥16.73 mmol/L). Cox regression models were used to analyze the influence of cumulative non-HDL-C burden on ASCVD risk., Results: We identified 1,134 incident ASCVD cases during a mean of 4.89 years of follow-up. Multivariable adjusted analysis revealed that compared with no exposure, cumNon-HDL-C duration 2, 4 and 6 years increased ASCVD risk by 26% (HR: 1.26, 95% CI: 1.07-1.47), 56% (HR: 1.56, 95% CI: 1.31-1.86) and 91% (HR: 1.91, 95% CI: 1.59-2.31) respectively; The hazard ratios (HRs) for the fourth and fifth versus lowest quintile of cumNon-HDL-C concentration were 1.25 and 1.72 for ASCVD. Each standard deviation increment in cumNon-HDL-C concentration was associated with a 10% increased risk of ASCVD., Conclusion: Long-term and higher cumNon-HDL-C were all significantly associated with an increased risk of ASCVD independent of single non-HDL-C level., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Guan, Shi, Xu, Chen, Zhang, Dong, Gao, Wu and Xia.)

Aims: This study aimed to investigate the efficacy and safety of CSP in patients with a high percentage of ventricular pacing and heart failure with HFmrEF., Methods: Patients who underwent CSP for HFmrEF and ventricular pacing >40% were consecutively enrolled from January 2018 to May 2021. All participants were followed up at least 12 months. Clinical data including cardiac performance and lead outcomes were compared before and after the procedure. Left ventricular ejection fraction (LVEF) was measured using the biplane Simpson's method. HFmrEF was defined as heart failure with the LVEF ranging from 41%-49%., Results: CSP was successfully performed in 64 cases (96.97%), which included 16 cases of left bundle branch pacing (LBBP) and 48 cases of His bundle pacing (HBP). After a mean of 23.12 ± 8.17 months follow-up, NYHA classification ( P  < 0.001), LVEF (42.45 ± 1.84% vs. 49.97 ± 3.57%, P  < 0.001) and left ventricular end diastolic diameter (LVEDD) (55.59 ± 6.17 mm vs. 51.66 ± 3.48 mm, P  < 0.001) improved significantly. During follow-up, more than half (39/64,60.9%) of patients returned to normal LVEF and LVEDD with complete reverse remodeling. The pacing threshold in LBBP was lower (0.90 ± 0.27 V@0.4 ms vs. 1.61 ± 0.71 V@0.4 ms, P  < 0.001) than that in HBP. No perforation, electrode dislodging, thrombosis or infection was observed during follow-up., Conclusions: CSP could improve the clinical outcomes in patients with HFmrEF and a high percentage of ventricular pacing. LBBP might be a better choice because of its feasibility and safety, especially in patients with infranodal atrioventricular block., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Zhang, Zhao, Yang, Ma, Ma, Zhao, Xia, Gao, and Dong.)

Flowering transition is tightly coordinated by complex gene regulatory networks, in which AGAMOUS-LIKE 16 (AGL16) plays important roles. Here, we identified the molecular function and binding properties of AGL16 and demonstrated its partial dependency on the SUPPRESSOR OF CONSTANS 1 (SOC1) function in regulating flowering. AGL16 bound to promoters of more than 2,000 genes via CArG-box motifs with high similarity to that of SOC1 in Arabidopsis (Arabidopsis thaliana). Approximately 70 flowering genes involved in multiple pathways were potential targets of AGL16. AGL16 formed a protein complex with SOC1 and shared a common set of targets. Intriguingly, only a limited number of genes were differentially expressed in the agl16-1 loss-of-function mutant. However, in the soc1-2 knockout background, AGL16 repressed and activated the expression of 375 and 182 genes, respectively, with more than a quarter bound by AGL16. Corroborating these findings, AGL16 repressed the flowering time more strongly in soc1-2 than in the Col-0 background. These data identify a partial inter-dependency between AGL16 and SOC1 in regulating genome-wide gene expression and flowering time, while AGL16 provides a feedback regulation on SOC1 expression. Our study sheds light on the complex background dependency of AGL16 in flowering regulation, thus providing additional insights into the molecular coordination of development and environmental adaptation., Competing Interests: Conflict of interest statement. None declared., (© American Society of Plant Biologists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Both metastasis and immune resistance are huge obstacle in lung adenocarcinoma (LUAD) treatment. Multiple studies have shown that the ability of tumor cells to resist anoikis is closely related to the metastasis of tumor cells., Methods: In this study, the risk prognosis signature related to anoikis and immune related genes (AIRGs) was constructed by cluster analysis and the least absolute shrinkage and selection operator (LASSO) regression by using The Cancer Genome Atlas (TCGA) Program and the Gene Expression Omnibus (GEO) database. Kaplan-Meier (K-M) curve described the prognosis in the different groups. Receiver operating characteristic (ROC) was applied to evaluate the sensitivity of this signature. Principal component analysis (PCA), t-distributed stochastic neighbor embedding (t-SNE), independent prognostic analysis, and nomogram were utilized to assess the validity of the signature. In addition, we used multiple bioinformatic tools to analyze the function between different groups. Finally, mRNA levels were analyzed by quantitative real-time PCR (qRT-PCR)., Results: The K-M curve showed a worse prognosis for the high-risk group compared to that for the low-risk group. ROC, PCA, t-SNE, independent prognostic analysis and nomogram showed well predictive capabilities. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that differential genes were mainly enriched in immunity, metabolism, and cell cycle. In addition, multiple immune cells and targeted drugs differed in the two risk groups. Finally, we found that the mRNA levels of AIRGs were remarkably different in normal versus cancer cells., Conclusions: In short, we established a new model about anoikis and immune, which can well predict prognosis and immune response., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-22-2550/coif). The authors have no conflicts of interest to declare., (2023 Translational Cancer Research. All rights reserved.)

To develop the structural and functional modeling chemistry of [NiFe]-H 2 ases, a series of new biomimetics for the active site of [NiFe]-H 2 ases have been prepared by various synthetic methods. Treatment of the mononuclear Ni complex (pnp)NiCl 2 (pnp = (Ph 2 PCH 2 ) 2 NPh) with (dppv)Fe(CO) 2 (pdt) (dppv = 1,2-(Ph 2 P) 2 C 2 H 2 , pdt = 1,3-propanedithiolate) and KPF 6 gave the dicarbonyl complex [(pnp)Ni(pdt)Fe(CO) 2 (dppv)](PF 6 ) 2 ([1](PF 6 ) 2 ). Further treatment of [1](PF 6 ) 2 and [(dppe)Ni(pdt)Fe(CO) 2 (dppv)](BF 4 ) 2 (dppe = 1,2-(Ph 2 P) 2 C 2 H 4 ) with the decarbonylation agent Me 3 NO and pyridine afforded the novel sp 3 C-Fe bond-containing complexes [(pnp)Ni(SCH 2 CH 2 CHS)Fe(CO)(dppv)]PF 6 ([2]PF 6 ) and [(dppe)Ni(SCH 2 CH 2 CHS)Fe(CO)(dppv)]BF 4 ([3]BF 4 ). More interestingly, the first t -carboxylato complexes [(pnp)Ni(pdt)Fe(CO)( t -O 2 CR)(dppv)]PF 6 ([4]PF 6 , R = H; [5]PF 6 , R = Me; [6]PF 6 , R = Ph) could be prepared by reactions of [1]PF 6 with the corresponding carboxylic acids RCO 2 H in the presence of Me 3 NO, whereas further reactions of [4]PF 6 -[6]PF 6 with aqueous HPF 6 and 1.5 MPa H 2 gave rise to the μ-hydride complex [(pnp)Ni(pdt)Fe(CO)(μ-H)(dppv)]PF 6 ([7]PF 6 ). Except for H 2 activation by t -carboxylato complexes [4]PF 6 -[6]PF 6 to give a μ-hydride complex ([7]PF 6 ), the sp 3 C-Fe bond-containing complex [2]PF 6 was found to be a catalyst for proton reduction to H 2 under CV conditions. Furthermore, the chemical reactivity of the μ-hydride complex [7]PF 6 displayed in the e - transfer reaction with FcPF 6 in the presence of CO, the H 2 evolution reaction with the protonic acid HCl, and the H - transfer reaction with N -methylacridinium hexafluorophosphate ([NMA]PF 6 ) was systematically studied. As a result, a series of the expected products such as H 2 , ferrocene, the dicarbonyl complex [1](PF 6 ) 2 , the μ-chloro complex [(pnp)Ni(pdt)Fe(CO)(μ-Cl)(dppv)]PF 6 ([8]PF 6 ), the t -MeCN-coordinated complex [(pnp)Ni(pdt)Fe(CO)( t -MeCN)(dppv)](PF 6 ) 2 ([9](PF 6 ) 2 ) and the H - transfer product AcrH 2 were produced. While all the newly prepared model complexes were structurally characterized by spectroscopic methods, the molecular structures of some of their representatives were confirmed by X-ray crystallography.

The iminoacylation of alkenes via photoredox N-heterocyclic carbene catalysis is developed with the employment of alkene-tethered α-imino-oxy acids and acyl imidazoles. The corresponding substituted 3,4-dihydro-2 H -pyrroles were afforded in moderate to good yields with good to high diastereoselectivities in most cases. The reaction involves the 5- exo -trig radical cyclization of an alkene-tethered iminyl radical and the following coupling with a ketyl radical from acyl imidazole under NHC catalysis.

Objective: To explore the transcriptional gene expression profile up-regulated in human macrophages stimulated by interferon-γ (IFN-γ) and the underlying intracellular signaling mechanisms., Methods: RNA-seq was used to sequence and compare the differential gene expression profiles of human macrophage cell line U937 before and after IFN-γ stimulation, and the significantly up-regulated genes were screened out, which were verified by fluorescence-based real-time quantitative polymerase chain reaction (qPCR) in U937 and THP1 cell lines, respectively. JAK/STAT, MAPK/ERK and PI3K/AKT pathway inhibitors were added to simultaneously to the cultured U937 cells upon IFN-γ priming to detect their effects on the expressions of the up-regulated genes to explore the key regulatory mechanisms., Results: RNA-seq and qPCR results showed that, the well-recognized chemokines CXCL9, CXCL10 and CXCL11, the APOL family including APOL1, APOL2, APOL3, APOL4, APOL6 and GBP family GBP1, GBP2, GBP3, GBP4 and GBP5 as well were significantly up-regulated in IFN-γ-stimulated U937 cells. JAK/STAT3 pathway inhibitor inhibited the upregulation of APOL1, APOL4, GBP1, GBP4 and GBP5 genes induced by IFN-γ, while MAPK/ERK pathway inhibitor inhibited the upregulation of CXCL10 gene. PI3K/AKT pathway inhibitor inhibited the upregulation of APOL1,APOL4, APOL6, GBP1 and GBP5 genes induced by IFN-γ, all three signal pathway inhibitors could inhibit the upregulation of CXCL9 gene, and none of them could inhibit the upregulation of APOL3 gene., Conclusion: Upon IFN-γ stimulation, some family molecules of APOL and GBP in macrophages are significantly up-regulated, and PI3K/AKT, JAK/STAT3 and MAPK/ERK pathways have positive regulation on their expressions, respectively.

An efficient radical annulation of N -arylacrylamides with disulfides is developed for the synthesis of sulfurated oxindoles. The reaction occurs in a facile manner using CoBr 2 as both an initiator and a promoter for the first time and (NH 4 ) 2 S 2 O 8 as the oxidant. By controlling the CoBr 2 /(NH 4 ) 2 S 2 O 8 ratio, a wide range of sulfurated and brominated/sulfurated oxindoles are selectively prepared in good to excellent yields. The present protocol is simple and highly atom economical, and can tolerate a broad range of substrates.

Pollen longevity is critical for plant pollination and hybrid seed production, but few studies have focused on pollen longevity. In this study, we identified an Arabidopsis thaliana gene, Protein associated with lipid droplets (PALD), which is strongly expressed in pollen and critical for the regulation of pollen longevity. PALD was expressed specifically in mature pollen grains and the pollen tube, and its expression was upregulated under dry conditions. PALD encoded a lipid droplet (LD)-associated protein and its N terminus was critical for the LD localization of PALD. The number of LDs and diameter were reduced in pollen grains of the loss-of-function PALD mutants. The viability and germination of the mature pollen grains of the pald mutants were comparable with those of the wild-type, but after the pollen grains were stored under dry conditions, pollen germination and male transmission of the mutant were compromised compared with those of the wild-type. Our study suggests that PALD was required for the maintenance of LD quality in mature pollen grains and regulation of pollen longevity., (© 2022 The Authors. New Phytologist © 2022 New Phytologist Foundation.)

Objective: This study aimed to explore the outcomes of His-Purkinje conduction system pacing (HPCSP) and to screen the predictors of left ventricular (LV) complete reverse remodeling in patients with true left bundle branch block (LBBB) and heart failure with reduced ejection fraction (HFrEF)., Methods: Patients who underwent HPCSP for true LBBB and HFrEF from April 2018 to August 2020 were consecutively enrolled. All participants were followed up for at least 1 year. Thrombosis, infection, lead dislodgement, perforation, and other complications were observed after HPCSP. Clinical data, including echocardiographic parameters, electrocardiogram measurements, and cardiac function, were assessed before and after the procedure., Results: A total of 46 patients were enrolled. HPCSP was successfully deployed in 42 cases (91.30%), which included 37 cases with His bundle pacing (HBP) and 5 cases with left bundle branch pacing (LBBP). The QRS duration decreased significantly (169.88 ± 19.17 ms vs. 113.67 ± 20.68 ms, P < 0.001). Left ventricular end-systolic volume (LVESV) (167.67 ± 73.20 ml vs. 85.97 ± 62.24 ml, P < 0.001), left ventricular end-diastolic diameter (LVEDD) (63.57 ± 8.19 mm vs. 55.46 ± 9.63 mm, P = 0.003) and left ventricular ejection fraction (LVEF) (26.52 ± 5.60% vs. 41.86 ± 11.56%, P < 0.001) improved dramatically. Complete reverse remodeling of the LV with normalized LVEF and LVEDD was found in nearly half of the patients (45.24%). A short QRS duration after HPCSP was a strong predictor of normalized LVEF and LVEDD ( P < 0.001). The thresholds increased markedly in two patients approximately 6 months after HBP. No patients died during the total follow-up period of 20.07 ± 6.45 months., Conclusion: Complete reverse remodeling of the LV could be found in nearly half of the patients with HFrEF and true LBBB after HPCSP, and the short QRS duration after HPCSP was a strong predictor., 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 Guan, Li, Zhao, Zhao, Yang, Dai, Dai, Gao, Xia and Dong.)

Myelin damage and abnormal remyelination processes lead to central nervous system dysfunction. Glial activation-induced microenvironment changes are characteristic features of the diseases with myelin abnormalities. We previously showed that ginsenoside Rg1, a main component of ginseng, ameliorated MPTP-mediated myelin damage in mice, but the underlying mechanisms are unclear. In this study we investigated the effects of Rg1 and mechanisms in cuprizone (CPZ)-induced demyelination mouse model. Mice were treated with CPZ solution (300 mg· kg -1 · d -1 , ig) for 5 weeks; from week 2, the mice received Rg1 (5, 10, and 20 mg· kg -1 · d -1 , ig) for 4 weeks. We showed that Rg1 administration dose-dependently alleviated bradykinesia and improved CPZ-disrupted motor coordination ability in CPZ-treated mice. Furthermore, Rg1 administration significantly decreased demyelination and axonal injury in pathological assays. We further revealed that the neuroprotective effects of Rg1 were associated with inhibiting CXCL10-mediated modulation of glial response, which was mediated by NF-κB nuclear translocation and CXCL10 promoter activation. In microglial cell line BV-2, we demonstrated that the effects of Rg1 on pro-inflammatory and migratory phenotypes of microglia were related to CXCL10, while Rg1-induced phagocytosis of microglia was not directly related to CXCL10. In CPZ-induced demyelination mouse model, injection of AAV-CXCL10 shRNA into mouse lateral ventricles 3 weeks prior CPZ treatment occluded the beneficial effects of Rg1 administration in behavioral and pathological assays. In conclusion, CXCL10 mediates the protective role of Rg1 in CPZ-induced demyelination mouse model. This study provides new insight into potential disease-modifying therapies for myelin abnormalities., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)

Ethnopharmacological Relevance: Korean red ginseng (KRG), a processed product of Panax ginseng C. A. Mey, show significant anti-depressive effect in clinic. However, its mechanism is still unclear., Aim of the Study: Gap junction intercellular communication (GJIC) dysfunction is a potential pathogenesis of depression. Therefore, this study's objective is to investigate whether the antidepressant effect of KRG is related to GJIC., Materials and Methods: Rat were restraint 8 h every day for 28 consecutive days to prepare depression models, and meanwhile, rats were intragastrically administrated with normal saline, KRG solutions (25, 50 or 100 mg/kg) or fluoxetine (10 mg/kg) 1 h before stress. The behavioral performance was determined by forced swimming test, sucrose preference test and open field test. GJIC was determined by the Lucifer yellow (LY) diffusion distance in prelimb cortex (PLC). In addition, the level of Cx43, one of executors of GJIC, was tested by Western blot. To find out the protective effect of KRG against GJIC dysfunction directly, rats were intracranially injected with carbenoxolone (CBX, blocker of GJIC), and meanwhile normal saline, KRG (100 mg/kg) or fluoxetine (10 mg/kg) was administered daily. The behavioral performance of these rats was detected, and the LY localization injection PLC area was used to detect the gap junction function., Results: Chronic resistant stress (CRS) induced depressive symptoms, as manifested by prolonged immobility time in forced swimming test and decreased sucrose consumption ratio. Administration of KRG alleviated these depressive symptoms significantly. GJIC determination showed that KRG improved the LY diffusion and increased Cx43 level in prefrontal cortex (PFC) significantly, indicated that GJIC dysfunction was alleviated by the treatment of KRG. However, the astrocytes number was also increased by the treatment of KRG, which maybe alleviate depression-like symptoms by increasing the number of astrocytes rather than improving GJIC. Injection of CBX produced depressive symptoms and GJIC dysfunction, as manifested by decreased sucrose consumption ratio and prolonged immobility time in forced swimming test, but no astrocytes number changes, KRG also reversed depressive symptoms and GJIC dysfunction, suggested that the improvement of depressive-like symptoms was improved by GJIC., Conclusions: KRG alleviate depressive disorder by improving astrocytic gap junction function., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To investigate the effects and mechanisms of allogeneic epidermal stem cells (ESCs) on the survival of allogeneic full-thickness skin grafts in nude mice with full-thickness skin defect wounds. Methods: Experimental research methods were applied. Primary ESCs that appeared paving stone-like after being cultured for 7 d were obtained by enzymatic digestion method from one 4-week-old male BALB/c-NU nude mouse (the same strain, age, and sex below). The cells of third passage were identified by flow cytometry to positively express ESC marker CD44 and negatively express CD45, meanwhile, the positive expression of ESC markers of p63 and integrin 6α, and negative expression of CD71 were identified by immunofluorescence method. The ESCs of third passage in the logarithmic growth phase were used for the following experiments. Twenty-six nude mice were equally divided into phosphate buffered saline (PBS) group and ESCs group according to the random number table. A full-thickness skin defect wound was made on the back of each nude mouse, and then the wounds of the two groups were sprayed with equal volumes of PBS and ESCs, respectively. The wounds were transplanted with full-thickness skin grafts cut from the backs of 4 other nude mice. Each ten nude mice from the two groups were selected, the wound healing and skin survival on post surgery day (PSD) 0 (immediately), 3, 7, 14, and 21 were observed, and the survival ratio and shrinkage rate of skin grafts on PSD 3, 7, 14, and 21 were calculated (the number of sample was the number of surviving skin grafts at each time point); the blood perfusion in the skin grafts on PSD 3, 7, and 14 was detected by the laser speckle blood flow imager, and the blood flow ratio of nude mice skin grafts in ESCs group to PBS group at each time point was calculated (the number of sample was the pair number of surviving skin grafts in group pairing at each time point). The skin graft tissue of each 3 nude mice remained in the two groups were collected on PSD 7, and the mRNA expressions and protein expressions of tumor necrosis factor α (TNF-α), interleukin 8 (IL-8), IL-10, type Ⅰ collagen, type Ⅲ collagen, and matrix metalloproteinase 9 (MMP-9) in the tissue were detected by real-time fluorescent quantitative reverse transcription polymerase chain reaction and Western blotting, respectively. Data were statistically analyzed with Log-rank test, analysis of variance for repeated measurement, one-way analysis of variance, independent sample t test, and Bonferroni correction. Results: Taking the condition on PSD 0 as a reference, the wounds of nude mice in the two groups healed gradually on PSD 3, 7, 14, and 21, and the shrinkage of skin grafts was gradually obvious. Among them, the shrinkage healing of wound of nude mice in PBS group was more significant than that in ESCs group. On PSD 3, the skin graft of 1 nude mouse failed in ESCs group, while the skin graft of 3 nude mice failed in PBS group. On PSD 7, the skin graft of another nude mouse failed in PBS group. The survival ratio of skin grafts of nude mice in the two groups was similar on PSD 3, 7, 14, and 21 ( P >0.05). On PSD 3, 7, 14, and 21, the shrinkage rates of skin grafts of nude mice in ESCs group were (9.2±0.4)%, (19.7±1.2)%, (53.6±3.5)%, and (62.2±5.1)%, respectively, which was significantly lower than (11.0±0.9)%, (47.8±2.8)%, (86.1±7.1)%, and (89.7±9.0)% in PBS group ( t =5.719, 26.650, 11.940, 7.617, P <0.01). On PSD 3, 7, and 14, blood perfusion signals were observed in the skin grafts of nude mice in the two groups. The average blood perfusion ratios of the skin grafts of nude mice in ESCs group to PBS group were greater than 1, and there was no statistically significant difference in the overall comparison of 3 time points ( P >0.05). On PSD 7, compared with those of PBS group, the mRNA and protein expressions of TNF-α, IL-8, type Ⅰ collagen, and type Ⅲ collagen in the skin graft tissue of nude mice in ESCs group were significantly reduced, while the mRNA and protein expressions of IL-10 and MMP-9 in the skin graft tissue of nude mice in ESCs group were significantly increased (in mRNA comparison, t =2.823, 2.934, 2.845, 2.860, 3.877, 2.916, P <0.05). Conclusions: Allogeneic ESCs can reduce the shrinkage of allogeneic full-thickness skin grafts transplanted on full-thickness skin defect wounds in nude mice, promote the formation of new blood vessels between the skin graft and the wound, reduce inflammation and collagen protein expression, and promote the expression of MMP-9, thus improving the survival quality of skin grafts.

Objective: To analyze the impact of cancer on the recurrence rate of atrial fibrillation (AF) after AF radiofrequency ablation and further evaluate the feasibility of radiofrequency ablation therapy in cancer patients with AF. Methods: This study was a single-center, retrospective study. Cancer patients with AF undergoing radiofrequency ablation for the first time in the First Affiliated Hospital of Dalian Medical University from May 30, 2008 to September 30, 2018 were included (cancer group). AF patients without cancer undergoing radiofrequency ablation for the first time during the same period served as non-cancer group. Clinical data including age, gender, past history, cancer and AF-related parameters, etc. were analyzed. Patients were followed up after radiofrequency ablation. The primary endpoints were AF recurrence or all-cause death. Kaplan-Meier survival analysis was used to analyze the effect of cancers on the recurrence after AF ablation. The multivariate cox regression analysis was further applied to correct for other confounding factors to analyze whether the impact of cancers on the recurrence of atrial fibrillation was statistically significant. Results: A total of 90 patients were enrolled, there were 30 patients in the cancer group (mean age (64.8±6.6) years, 16 (53.3%) males) and 60 patients in the non-cancer group (mean age (63.6±6.2) years, 32 (53.3%) males). Clinical data, such as age, gender, and cancer treatment, were similar between the two groups. During an average follow-up period of (328.7±110.2) days, there were 6 AF recurrences (recurrence rate 20.0%) in the cancer group, and 17 AF recurrences (recurrence rate 28.3%) in the control group. AF recurrence rate was similar between the two groups ( P >0.05). During the follow-up period, there was no all-cause death in the two groups. Kaplan-Meier survival analysis showed that cancer was not related to AF recurrence after radiofrequency ablation ( P = 0.383). After adjusting for other confounding factors, the multivariate Cox regression analysis showed that cancer was not an independent predictor of AF recurrence after radiofrequency ablation ( HR =0.508, 95% CI : 0.192-1.342, P = 0.172). Conclusions: The combination of cancer has no impact on the recurrence of AF after radiofrequency ablation. For cancer patients with AF, radiofrequency ablation therapy can be considered as a feasible heart rhythm control treatment strategy.

Introduction: The efficacy and safety of his-purkinje system pacing (HPSP) upgrades in patients with pacing-induced cardiomyopathy (PICM) and atrial fibrillation (AF) are still unknown., Methods and Results: Patients with PICM were continuously enrolled from January 2018 to March 2020. All patients were further divided into AF subgroup and sinus rhythm subgroup. Clinical data including echocardiographic examination parameters, electrocardiogram (ECG) measurements, and New York Heart Association (NYHA) classification, were assessed before and after the procedure. The HPSP upgrades, including his bundle pacing (HBP) and left bundle branch pacing (LBBP) were completed in 34 of 36 (94%) patients, Complications including electrode dislodged, perforation, infection or thrombosis were not observed in the perioperative period. During a mean of 11.52 ± 5.40 months of follow-up. The left ventricular ejection fraction (LVEF) increased significantly (33.76 ± 7.54 vs 40.41 ± 9.06, P < 0.001), and the QRS duration decreased (184.22 ± 23.76 ms vs 120.52 ± 16.67 ms, P < 0.001) after the upgrades. LVEDD reversed from 59.29 ± 7.74 mm to 53.91 ± 5.92 mm (P < 0.001), and the NYHA functional class also improved to 2.00 ± 0.76 from 2.55 ± 0.91 at the first follow-up (P < 0.001). The left atrium (LA) size also slightly decreased compared to the initial state (47.44 ± 7.14 mm VS 45.56 ± 7.78, P = 0.010). BNP significantly decreased from a median value of 458.06(256.35-755.10) to 172.31(92.69-552.14) (P = 0.004). The threshold did not increase significantly (1.18 ± 0.76 mv@0.4 ms vs 1.26 ± 0.91mv @ 0.4 ms, P = 0.581). These improvements in patients with AF were similar with those in patients without AF (P > 0.05)., Conclusions: HPSP upgrades improved the heart performance and reversed the left ventricular remodeling in patients suffering from PICM with or without AF, and it should be a promising choice in these patients., (Copyright © 2021. Published by Elsevier B.V.)

An efficient aerobic iron-catalyzed annulation of unsaturated carboxylic acids with disulfides has been developed. This procedure proceeds using FeCl 3 as the catalyst and KI as an iodine source under an air atmosphere, which provides practical access to a wide range of substituted γ-lactone derivatives. The disclosed method is quite simple, highly atom-economic, environmentally friendly, and tolerates a broad substrate scope.

Objective: To investigate the efficacy and safety of His-bundle pacing (HBP) compared with the traditional biventricular pacing (BVP) on patients with brady-arrhythmias, who suffer from permanent atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF)., Methods: All patients with brady-arrhythmias, permanent AF and HFrEF were continuously enrolled from January 2017 to July 2019 and followed up for at least 12 months. The differences in QRS duration (QRSd), New York Heart Association (NYHA) classification, left ventricular ejection fraction (LVEF), tricuspid regurgitation grade, mitral regurgitation grade, left ventricular end-diastolic diameter (LVEDD), and left atrial size were compared., Results: A total of 52 patients were enrolled: 37 patients were with HBP and 15 patients with BVP. There was no electrode dislodged, perforation, infection or thrombosis during the follow-up of 18.12 ± 4.45 months. The success rate for HBP implantation was 88.10%. The capture threshold of his-bundle and the threshold of the left ventricular lead remained stable during follow-up. LVEF increased to higher than 50% in 11 patients with HBP (29.73%). The NYHA classification (both p < .001), LVEF (both p < .001) and LVEDD improved significantly during the follow-up in both groups. NYHA (p = .030), LVEF (p = .013), and LVEDD (p = .003) improved in patients with HBP compared with BVP., Conclusion: HBP was safe and more effective in improving the cardiac function and remodeling in patients with brady-arrhythmias, permanent AF and HFrEF compared with BVP., (© 2021 Wiley Periodicals LLC.)

The outbreak of the 2019 novel coronavirus disease (COVID-19) has impacted the mental health of healthcare providers at the frontline. Therefore, we conducted this study to estimate the prevalence rate of anxiety and insomnia and identify associated risk factors among healthcare workers in Jilin, China, during the period from January 25 to February 25, 2020. Zung's Self-Reported Anxiety Scale (SAS) and the Insomnia Severity Index (ISI) scale were used to diagnose anxiety and insomnia, respectively. Associated risk factors were identified through a multivariate logistic regression model. A total of 300 healthcare workers were invited and 236 completed the study. Of them, 234 (99.15%) were medical workers, 197 (83.47%) were working at frontline departments, and 159 (67.37%) were fighting against COVID-19. Fifty-seven respondents (24.15%) had anxiety (SAS index score ≥45) and 94 (39.83%) had insomnia (ISI score ≥8). Based on the multivariate analysis, contact with people from Hubei province during work (no vs not clear) [OR=0.25, 95%CI: 0.10-0.61] and personal protective equipment (PPE) (not in place vs in place) [OR=6.22, 95%CI: 2.23-17.40] were significantly correlated with anxiety. PPE (not in place vs in place) was the only significant risk factor of insomnia [OR=10.56, 95%CI: 4.00-27.87]. The prevalence of anxiety and insomnia was high in our study, reflecting the psychological impact of COVID-19 on healthcare workers. The unavailability of PPE in place was a significant risk factor of both anxiety and insomnia.

Plant genomes encode numerous proteins with obscure features (POFs) that lack recognized domains or motifs. However, there is little functional information for POFs even in Arabidopsis because biochemical, physiological, and genetic assay are required for the functional annotations of POFs. Here, we identified a small gene family, the endoplasmic reticulum-localized POF (ERP) family, in Arabidopsis . Phylogenetic analysis revealed that the number of ERP family members was conserved in the plant kingdom, suggesting strong selective pressure was imposed on ERP family during plant evolution. No recognizable domains were identified in the predicted ERP proteins, except for the N-terminal signal peptide. ERPs were found to be widely expressed during Arabidopsis development and showed endoplasmic reticulum localization. It was reported that ERP1 is an inositol-1,4,5-trisphosphate 5-phosphatase (5PTase), but ERP1 could not substitute for At5PTase12 in precocious pollen germination, indicating that ERP1 did not have the similar functions as At5PTase12 in inositol 1,4,5-trisphosphate [Ins(1,4,5) P3 ] metabolism. Further studies are needed to dissect the functions of ERP family proteins in Arabidopsis development.

Background: To clarify the appropriate initial dosage of heparin during radiofrequency catheter ablation (RFCA) in patients with atrial fibrillation (AF) receiving uninterrupted nonvitamin K antagonist oral anticoagulant (NOAC) treatment., Methods: A total of 187 consecutive AF patients who underwent their first RFCA in our center were included. In the warfarin group (WG), an initial heparin dose of 100 U/kg was administered (control group: n = 38). The patients who were on NOACs were randomly divided into 3 NOAC groups (NG: n = 149), NG110, NG120, and NG130, and were administered initial heparin doses of 110 U/kg, 120 U/kg, and 130 U/kg, respectively. During RFCA, the activated clotting time (ACT) was measured every 15 min, and the target ACT was maintained at 250-350 s by intermittent heparin infusion. The baseline ACT and ACTs at each 15-min interval, the average percentage of measurements at the target ACT, and the incidence of periprocedural bleeding and thromboembolic complications were recorded and analyzed., Results: There was no significant difference in sex, age, weight, or baseline ACT among the four groups. The 15 min-ACT, 30 min-ACT, and 45 min-ACT were significantly longer in the WG than in NG110 and NG120. However, no significant difference in 60 min-ACT or 75 min-ACT was detected. The average percentages of measurements at the target ACT in NG120 (82.2 ± 23.6%) and NG130 (84.8 ± 23.7%) were remarkably higher than those in the WG (63.4 ± 36.2%, p = 0.007, 0.003, respectively). These differences were independent of the type of NOAC. The proportion of ACTs in 300-350 s in NG130 was higher than in WG (32.4 ± 31.8 vs. 34.7 ± 30.6, p = 0.735). Severe periprocedural thromboembolic and bleeding complications were not observed., Conclusions: For patients with AF receiving uninterrupted NOAC treatment who underwent RFCA, an initial heparin dosage of 120 U/kg or 130 U/kg can provide an adequate intraprocedural anticoagulant effect, and 130 U/kg allowed ACT to reach the target earlier., Trial Registration: Registration number: ChiCTR1800016491, First Registration Date: 04/06/2018 (Chinese Clinical Trial Registry http://www.chictr.org.cn/index.aspx ).

Background: Post-stroke depression (PSD) is one of the most common stroke complications with high morbidity. Researchers have done much clinical research on Traditional Chinese Medicine (TCM) treatment, but very little research on diagnosis. Based on the thought of combination of disease and syndrome, this study will establish a unified and objective quantitative diagnosis model of TCM syndromes of PSD, so as to improve the clinical diagnosis and treatment of PSD., Objective: First: To establish a unified and objective quantitative diagnosis model of TCM syndromes in PSD under different disease courses, and identify the corresponding main, secondary, and concurrent symptoms, which are based on the weighting factor of each TCM symptom. Second: To find out the relationship between different stages of PSD and TCM syndromes. Clarify the main syndrome types of PSD under different stages of disease. Reveal the evolution and progression mechanism of TCM syndromes of PSD., Methods and Analysis: This is a retrospective study of PSD TCM diagnosis. Three hundred patients who were hospitalized in the First Teaching Hospital of Tianjin University of TCM with complete cases from January 2014 to January 2019 are planned to be recruited. The study will mainly collect the diagnostic information from the cases, find the related indicators of TCM and Western medicine in PSD, and clarify the relationship between different disease stages and TCM syndromes. Finally, the PSD TCM syndrome quantitative diagnosis model will be established based on the operation principle of Back Propagation (BP) artificial neural network., Conclusion: To collect sufficient medical records and establish models to speed up the process of TCM diagnosis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)