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Peroxisome proliferator-activated receptor (PPAR) expression has been implicated in pathological states such as cancer, inflammation, diabetes, and neurodegeneration. We isolated natural PPAR agonists-eight 2,5-diketopiperazines-from the jellyfish-derived fungus Aspergillus flavus . Cyclo-(L-Pro-L-Phe) was the most potent PPAR-γ activator among the eight 2,5-DKPs identified. Cyclo-(L-Pro-L-Phe) activated PPAR-γ in Ac2F rat liver cells and SH-SY5Y human neuroblastoma cells. The neuroprotective effect of this partial PPAR-γ agonist was examined using the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, lactate dehydrogenase release, and the Hoechst 33342 staining assay in SH-SY5Y cells. Our findings revealed that cyclo-(L-Pro-L-Phe) reduced hydrogen peroxide-induced apoptosis as well as the generation of reactive oxygen species. Rhodamine 123 staining and western blotting revealed that cyclo-(L-Pro-L-Phe) prevented the loss of mitochondrial membrane potential and inhibited the activation of mitochondria-related apoptotic proteins, such as caspase 3 and poly (ADP-ribose) polymerase. Moreover, cyclo-(L-Pro-L-Phe) inhibited the activation and translocation of nuclear factor-kappa B. Thus, the partial PPAR-γ agonist cyclo-(L-Pro-L-Phe) demonstrated potential neuroprotective activity against oxidative stress-induced neurodegeneration in SH-SY5Y cells.

Antibody-mediated glomerulonephritis (AGN) is a clinical manifestation of many autoimmune kidney diseases for which few effective treatments exist. Chronic inflammatory circuits in renal glomerular and tubular cells lead to tissue damage in AGN. These cells are targeted by the cytokine IL-17, which has recently been shown to be a central driver of the pathogenesis of AGN. However, surprisingly little is known about the regulation of pathogenic IL-17 signaling in the kidney. Here, using a well-characterized mouse model of AGN, we show that IL-17 signaling in renal tubular epithelial cells (RTECs) is necessary for AGN development. We also show that Regnase-1, an RNA binding protein with endoribonuclease activity, is a negative regulator of IL-17 signaling in RTECs. Accordingly, mice with a selective Regnase-1 deficiency in RTECs exhibited exacerbated kidney dysfunction in AGN. Mechanistically, Regnase-1 inhibits IL-17-driven expression of the transcription factor IκBξ and, consequently, its downstream gene targets, including Il6 and Lcn2. Moreover, deletion of Regnase-1 in human RTECs reduced inflammatory gene expression in a IκBξ-dependent manner. Overall, these data identify an IL-17-driven inflammatory circuit in RTECs during AGN that is constrained by Regnase-1.

Excessive cytokine activity underlies many autoimmune conditions, particularly through the interleukin-17 (IL-17) and tumor necrosis factor-α (TNFα) signaling axis. Both cytokines activate nuclear factor κB, but appropriate induction of downstream effector genes requires coordinated activation of other transcription factors, notably, CCAAT/enhancer binding proteins (C/EBPs). Here, we demonstrate the unexpected involvement of a posttranscriptional "epitranscriptomic" mRNA modification [N6-methyladenosine (m 6 A)] in regulating C/EBPβ and C/EBPδ in response to IL-17A, as well as IL-17F and TNFα. Prompted by the observation that C/EBPβ/δ-encoding transcripts contain m 6 A consensus sites, we show that Cebpd and Cebpb mRNAs are subject to m 6 A modification. Induction of C/EBPs is enhanced by an m 6 A methylase "writer" and suppressed by a demethylase "eraser." The only m 6 A "reader" found to be involved in this pathway was IGF2BP2 (IMP2), and IMP2 occupancy of Cebpd and Cebpb mRNA was enhanced by m 6 A modification. IMP2 facilitated IL-17-mediated Cebpd mRNA stabilization and promoted translation of C/EBPβ/δ in response to IL-17A, IL-17F, and TNFα. RNA sequencing revealed transcriptome-wide IL-17-induced transcripts that are IMP2 influenced, and RNA immunoprecipitation sequencing identified the subset of mRNAs that are directly occupied by IMP2, which included Cebpb and Cebpd Lipocalin-2 ( Lcn2 ), a hallmark of autoimmune kidney injury, was strongly dependent on IL-17, IMP2, and C/EBPβ/δ. Imp2 -/- mice were resistant to autoantibody-induced glomerulonephritis (AGN), showing impaired renal expression of C/EBPs and Lcn2 Moreover, IMP2 deletion initiated only after AGN onset ameliorated disease. Thus, posttranscriptional regulation of C/EBPs through m 6 A/IMP2 represents a previously unidentified paradigm of cytokine-driven autoimmune inflammation., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Objective: To explore the clinicopathological and prognostic features of young onset patients with middle-low rectal cancer who received neoadjuvant chemoradiotherapy (NCRT). Methods: After NCRT, a total of 441 patients with primary middle-low rectal cancer treated with radical surgery at the Cancer Hospital, Chinese Academy of Medical Sciences (CHCAMS) from January 2004 to December 2016 were included. According to the age of disease onset, the patients were divided into the young group (51cases) and the middle-old group (390 cases), and the clinicopathological characteristics and survival of these patients were analyzed. Results: In the young group, 68.6% of patients received radical surgery within 7 weeks after NCRT, which was higher than 52.8% in the middle-old group ( P =0.047). The stage ypTNM Ⅲ in the young group was 51.0%, higher than 34.1% in the middle-old group ( P =0.027). The stage ypN+ in the young group was 51.0%, higher than 34.1% in the middle-old group ( P =0.047), The incidence of disease progression in the young group was 39.2%, higher than 25.1% in the middle-old group ( P =0.049). The incidence of distant metastasis in the young group was 35.3%, higher than 21.5% in the middle-old group( P =0.044). Most cases of disease progression occurred in the first 3 years after surgery for the young group, especially in the second year after surgery, the incidence of disease progression in the young group was 55.0%, higher than 26.5% in middle-old group ( P =0.025). The 3-year and 5-year disease-free survival (DFS) rates for the young group were 63.7% and 58.2%, lower than 81.0% and 74.3% in the middle-old group ( P =0.016), respectively. The 3-year and 5-year overall survival in the middle-old group (OS) rates for the young group were 85.4% and 69.2%, lower than 93.6% and 84.1% in the middle-old group ( P =0.033), respectively. The multivariate analysis showed that, response of primary tumor ( HR =4.804, 95% CI : 1.360-16.973) and total number of dissected lymph nodes ( HR =4.336, 95% CI: 1.739-10.809) in the young group were independent prognostic factors related to DFS. The total dissected number of lymph nodes( HR =3.295, 95% CI: 1.076-10.091)was an independent prognostic factor related to OS. In the middle-old group, response of primary tumor ( HR =2.626, 95% CI: 1.354-5.091), ypTNM stage (ypTNM Ⅲ: HR =5.837, 95% CI: 2.968-11.479) and tumor location distance from the anal verge ( HR =0.500, 95% CI: 0.308-0.812) were independent prognostic factors related to DFS. Lymphovascular invasion ( HR =0.500, 95% CI: 0.308-0.812) and ypTNM stage (ypTNM Ⅲ: HR =16.322, 95% CI: 5.049-52.771) were independent prognostic factors related to OS. Conclusions: Young onset rectal cancer patients are associated with shorter operation time interval, advanced pathological stage and poorer prognosis. More intensive adjuvant treatment and post-treatment surveillance should be conducted to young onset rectal cancer with NCRT.

Objective: To investigate the clinicopathological characteristics and prognosis of rectal cancer patients with pathological complete response and near complete response after neoadjuvant therapy. Methods: The clinicopathological data of patients who underwent neoadjuvant chemoradiotherapy plus radical surgery of rectal cancer in the Cancer Hospital of Chinese Academy of Medical Sciences from January 2004 to December 2016 were retrospectively collected. The clinicopathological characteristics and prognostic factor of patients with pathological complete response and near complete response were analyzed. Results: The clinical data of 142 patients were collected. There were 93 males and 49 females, aged from 24 to 81 years. The median disease-free survival was 53.9 months and the median overall survival was 55.0 months. Univariate analysis showed that the maximum diameter of scar or lesion, the status of lymph node metastasis and the distance between the lower edge of tumor and anal edge were associated with disease-free survival time; the maximum diameter of scar or lesion and the status of lymph node metastasis were associated with overall survival time. Multivariate Cox proportional hazards regression analysis showed that patients with scar or lesion diameter>3 cm ( HR =4.406,95% CI :1.619-12.006), positive lymph node metastasis status ( HR =4.102,95% CI :1.461-11.513) and tumor lower margin to anal margin distance ≤4 cm ( HR =18.171,95% CI :2.357-140.073) had shorter disease-free survival time.The patients with scar or lesion diameter>3 cm ( HR =8.573,95% CI :1.630-45.099) and lymph node metastasis status ( HR =4.721, 95% CI :1.068-20.860) had shorter overall survival time. Conclusions: The overall prognosis of patients with pathological complete response or near complete response after neoadjuvant therapy for rectal cancer is better. The distance between the lower margin of the tumor and the anal edge, the status of lymph node metastasis and the maximum diameter of scars or lesion were the related factors affecting the prognosis of patients with rectal cancer.

Measuring fluorescence lifetimes of fast-moving cells or particles have broad applications in biomedical sciences. This paper presents a dynamic fluorescence lifetime sensing (DFLS) system based on the time-correlated single-photon counting (TCSPC) principle. It integrates a CMOS 192 × 128 single-photon avalanche diode (SPAD) array, offering an enormous photon-counting throughput without pile-up effects. We also proposed a quantized convolutional neural network (QCNN) algorithm and designed a field-programmable gate array embedded processor for fluorescence lifetime determinations. The processor uses a simple architecture, showing unparallel advantages in accuracy, analysis speed, and power consumption. It can resolve fluorescence lifetimes against disturbing noise. We evaluated the DFLS system using fluorescence dyes and fluorophore-tagged microspheres. The system can effectively measure fluorescence lifetimes within a single exposure period of the SPAD sensor, paving the way for portable time-resolved devices and shows potential in various applications., Competing Interests: The authors declare no conflict of interest., (Published by The Optical Society under the terms of the Creative Commons Attribution 4.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI.)

To understand the effect of nitrogen from runoff during rainfall events for different land uses, sub-catchments A and B in the small Shipanqiu watershed in Zhong County, Chongqing-which were managed using different land use practices-were taken as research objects. Runoff flow and nitrogen levels at the outlet of the catchment were monitored. Sub-catchment A is an agroforestry-water complex and sub-catchment B is the site of traditional agriculture. EMC was used to evaluate the average concentration of runoff nitrogen during rainfall events, and the effect of this runoff nitrogen on the small watershed with different land use systems was analyzed. The results showed that the TN concentration in catchment B (1.37-15.17 mg·L -1 ) > catchment A (0.84-9.28 mg·L -1 ); the ratio of the first peak to the second peak in catchment A was 62%, which was far less than the 97% in catchment B; the average DN/TN values were 69% and 75% in catchments A and B, respectively; and the average NN/DN values were 67% and 80% in catchments A and B, respectively. The different land use practices have significant impacts on nitrogen loss. Compared with the catchment where traditional agricultural practices were followed, the agroforestry-water complex catchment effectively reduced the loss of nitrogen and decreased the first TN peak value and DN/TN and NN/DN values. This study provides a scientific basis for the prevention and control of non-point source pollution in small watersheds in the area of the Three Gorges Reservoir.

Intestinal fungi are critical for modulating host immune homeostasis and underlying mechanisms remain unclear. We show that dendritic cell (DC)-specific deficiency of casitas B-lineage lymphoma (c-Cbl) renders mice susceptible to dextran sodium sulfate (DSS)-induced colitis. Mechanistically, we identify that c-Cbl functions downstream of Dectin-2 and Dectin-3 to mediate the ubiquitination and degradation of noncanonical nuclear factor κB subunit RelB. Thus, c-Cbl deficiency in DCs promotes α-mannan-induced activation of RelB, which suppresses p65-mediated transcription of an anti-inflammatory cytokine gene, il10 , thereby aggravating DSS-induced colitis. Moreover, suppressing fungal growth with fluconazole or inhibition of RelB activation in vivo attenuates colitis in mice with DC-specific deletion of c-Cbl. We also demonstrate an interaction between c-Cbl and c-Abl tyrosine kinase and find that treatment with DPH, a c-Abl agonist, synergistically increases fungi-induced c-Cbl activation to restrict colitis. Together, these findings unravel a previously unidentified fungi-induced c-Cbl/RelB axis that sustains intestinal homeostasis and protects against intestinal inflammation., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Background and objective: Cancer is a life-threatening disease worldwide and current standard therapy cannot fulfill all clinical needs. Chinese herbal injections have been widely used for cancer in Chinese and Western hospitals in China. This study aimed to apply evidence mapping in order to provide an overview of the clinical application of Chinese herbal injections in cancer care based on randomized controlled trials, systematic reviews, and meta-analyses. Methods and results: Seven databases were systematically searched for eligible randomized controlled trials, systematic reviews, and meta-analyses for ten Chinese herbal injections used in cancer treatment and covered in the Chinese national essential health insurance program. Excel 2016 and RStudio were used to integrate and process the data. In total 366 randomized controlled trials and 48 systematic reviews and meta-analyses were included in the evidence mapping of herbal medicines including; Compound Kushen, Shenqi Fuzheng, Aidi, Kangai, Kanglaite, Xiaoaiping, Cinobufacin, Brucea javanica oil emulsion, Polyporus polysaccharide injection, and Astragalus polysaccharide for injection. Health insurance restricts the scope of clinical application for these herbal injections. The numbers of studies published increased, especially around 2013-2015. The most studied cancer types were lung cancer (118, 32.2%), colorectal cancer (39, 10.7%), and gastric cancer (39, 10.7%), and the most used injections were Compound Kushen (78, 21.3%), Shenqi Fuzheng (76, 20.8%), and Aidi (63, 17.2%). The most consistently reported benefits were observed for Compound Kushen, Shenqi Fuzheng, Aidi, and Kangai for tumor response, quality of life, myelosuppression, and enhancing immunity. Conclusion: The current evidence mapping provides an overview of the outcomes and effects of Chinese herbal injections used in cancer care, and offers information on their clinical application which warrants further evidence-based research in order to inform clinical and policy decision-making., 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. The reviewer JW declared a shared affiliation with the authors to the handling editor at time of review., (Copyright © 2021 Yang, Zhu, Shen, Zhai, Li, Fang, Xu, Gan, Yang, Ren, Zheng, Robinson and Liu.)

Porous coordination polymers with organic aminium as one of the guest species possess a potential application in dye adsorption and white-light material manufacture. Polycarboxylic acid with multiple COOH substituents tends to form this type of porous material (with metal ion). Here the solvothermal self-assembly between Cd 2+ and a hexacarboxylic acid creates such a porous material [(CH 3 ) 2 NH 2 ] 6 [Cd 3 (L) 2 ]·5DMF·3H 2 O (H 6 L = 3,4-di(3,5-dicarboxyphenyl)phthalic acid) 1. Total potential guest accessible void volume in 3-D 1 is found to be 4327 Å 3 . Based on its better porous structure and stability, the ability of 1 to adsorb organic dyes is investigated. It has been proved that (i) 1 can selectively adsorb cationic dyes as Azure A (AA + ) and/or Methylene Blue (MB + ), rather than neutral and anionic ones; (ii) the maximum adsorption capacity is 698.2 mg·g -1 for AA + and 573.2 mg·g -1 for MB + , respectively; and (iii) to the adsorption of AA + , it can be recycled for at least five rounds. Also, it is utilized to fabricate the while-light emitting material. Based on the blue-light emission of 1, the trace Eu 3+ and Tb 3+ ions are introduced into the pores of 1 successfully, obtaining a white-light emitting material Eu 3+ /Tb 3+ @1 (CIE chromaticity coordinates: (0.33, 0.32)). Meanwhile, Eu 3+ /Tb 3+ @1 is found to be a potential fluorescence photochromic material, showing a yellow-white-blue light emission. According to these investigations, the relationship between material structure and its adsorption property for dyes, the points that should be paid attention to in the construction of white-light emitting materials as well as the potential adsorption mechanism for dyes and rare earth ions are deeply discussed., 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 © 2021 Elsevier B.V. All rights reserved.)

Small nucleolar RNAs (snoRNAs) are thought to be exclusively nuclear and guide nucleotide modifications of ribosomal RNAs. Recently, more and more evidence has suggested that the nucleolus is a stress sensor for changes in growth status and that snoRNAs may orchestrate the response to environmental stress through molecular interactions outside of the nucleus. We previously showed that a box C/D snoRNA Bm-15 had both nuclear and cytoplasmic location in BmN4 cell line of the silkworm, Bombyx mori. To further study the functional roles of Bm-15, changes in expression level and cellular location of Bm-15 were examined in BmN4 cells subjected to serum starvation and ultraviolet (UV) ray radiation. Results indicated that total RNA level of Bm-15 was unchanged after 24 h serum starvation, but exhibited 3-fold increases in the cytoplasm, and the nuclear-to-cytosolic distribution ratio was reduced from 5:1 to 2:1. Moreover, UV radiation also causes rapid decline in nuclear Bm-15 and progressive cytoplasmic accumulation with a percentage of 22% and 57% after 6 and 24 h UV radiation. UV treatment results in a dramatic decrease in Bm-15 nuclear-to-cytosolic ratio from 7:1 to 2:1 and 2:1 to 1:20 after 6 and 24 h UV radiation, respectively. We show here for the first time that box C/D snoRNAs can translocate from the nucleus to the cytoplasm under the abiotic stress of nutritional deficiency and UV radiation. The rapid translocation of snoRNAs from nucleus to cytoplasm may slow down the maturation of rRNAs and synthesis of ribosomes to enhance the stress resistance of cells., (© 2021 International Federation for Cell Biology.)

Background: The efficacy and safety of proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors were confirmed by several clinical trials, but its effectiveness in routine clinical practice in China has not been evaluated. This study aims to describe the real world effectiveness of PCSK-9 inhibitors combined with statins compared with statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease (ASCVD)., Methods: This is a multi-center observational study, enrolled patients from 32 hospitals who underwent percutaneous coronary intervention (PCI) from January to June in 2019. There are 453 patients treated with PCSK-9 inhibitors combined with statins in PCSK-9 inhibitor group and 2,610 patients treated with statins-based lipid lowering therapies in statins-based group. The lipid control rate and incidence of major adverse cardiovascular events (MACE) over six months were compared between two groups. A propensity score-matched (PSM) analysis was used to balance two groups on confounding factors. Survival analysis using Kaplan-Meier methods was applied for MACE., Results: In a total of 3,063 patients, 89.91% of patients had received moderate or high-intensity statins-based therapy before PCI, but only 9.47% of patients had low-density lipoprotein cholesterol (LDL-C) levels below 1.4 mmol/L at baseline. In the PSM selected patients, LDL-C level was reduced by 42.57% in PCSK-9 inhibitor group and 30.81% ( P < 0.001) in statins-based group after six months. The proportion of LDL-C ≤ 1.0 mmol/L increased from 5.29% to 29.26% in PCSK-9 inhibitor group and 0.23% to 6.11% in statins-based group, and the proportion of LDL-C ≤ 1.4 mmol/L increased from 10.36% to 47.69% in PCSK-9 inhibitor group and 2.99% to 18.43% in statins-based group ( P < 0.001 for both). There was no significant difference between PCSK-9 inhibitor and statins-based treatment in reducing the risk of MACE (hazard ratio = 2.52, 95% CI: 0.49-12.97, P = 0.250)., Conclusions: In the real world, PCSK-9 inhibitors combined with statins could significantly reduce LDL-C levels among patients with very high risk of ASCVD in China. The long-term clinical benefits for patients received PCSK-9 inhibitor to reduce the risk of MACE is still unclear and requires further study., (Copyright and License information: Journal of Geriatric Cardiology 2021.)

The toxicity spectrum between Chinese and Caucasian patients with melanoma who were treated with BRAF inhibitors (BRAFi) may differ. The purpose of the present study was to assess the safety and tolerability of BRAFi and BRAFi-based combination therapies [MEK inhibitors (MEKi) or anti-programmed death-1 (PD-1) antibody] in Chinese patients with BRAF V600E/K mutation-positive metastatic melanoma. We also investigated whether treatment-related adverse events (AEs) correlated with the prognosis. This retrospective study collected data from 43 patients with BRAF V600E/K mutation-positive metastatic melanoma from a single Chinese cancer center. Of the 43 patients, 12 patients received BRAFi monotherapy, 12 patients received BRAFi+MEKi, and 19 patients received BRAFi combined with the anti-PD-1 antibody. The median follow-up time was 19 months. In the BRAFi group, the most common AEs were rashes, palmoplantar erythrodysesthesia, and arthralgia. Four out of 12 (30%) patients experienced grade 3-4 treatment-related AEs. All grades of AEs in the BRAFi+MEKi group were similar to the BRAFi group, except for higher pyrexia (58.3%) and fewer cutaneous AEs. Three out of 12 (25%) patients experienced grade 3-4 AEs, especially pyrexia (16.7%). In the BRAFi+anti-PD-1 antibody group, AEs were similar to the BRAFi group, except for an increased aminotransferase level (36.8%), increased bilirubin (31.6%), and hypothyroidism (15.8%). Eleven out of 19 (57.9%) patients experienced grade 3-4 AEs and four out of 19 (21%) patients discontinued the therapy due to AEs. Treatment-related hepatotoxicity (trHE), defined as an increase in either alanine aminotransferase (ALT), aspartate transaminase (AST), or bilirubin levels, was the only AE identified as a significant poor-prognosis indicator in this study. The median progression-free survival of patients with trHE (41.9%) was 8 months, whereas it was 18 months for those without trHE [ p = 0.046, hazard ratio (HR) = 2.116]. Moreover, this association was independent of medication regimens ( p = 0.014, HR = 2.971). The overall response rate of patients with trHE was significantly lower than those without trHE (44.4 vs. 60.0%, p = 0.024), and we observed a similar trend in patients treated with BRAFi, BRAFi+MEKi, and BRAFi+anti-PD-1 antibody. In conclusion, BRAFi and BRAFi-based combination therapies were tolerable with reversible AEs in Chinese patients with melanoma. The trHE in patients receiving BRAFi and BRAFi-based regimens might indicate a poor therapy-related prognosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Li, Ding, Li, Wen, Weng, Wang, Jiang and Zhang.)

Objective: To investigate the Effects of different dusting methods on pathological changes and cytokines in rat lung tissue. Methods: 84 healthy male SPF Wistar rats, were randomly divided into control group and dynamic dusting group, tracheal perfusion group, On the day 3, 14, 28, and 60 after the dust exposure, 7 rats in each group were randomly selected and killed. Record the weight of rats and calculate the lung coefficient; Observe the pathological changes of lung tissue by HE staining, Evaluate the pulmonary collagen fibrosis by Masson staining, observe The changes of area ratio of collagen fibers in lung tissue Sirius scarlet staining, Use enzyme-linked immunosorbent assay to detect the content of transforming growth factor (TGF) -β1 and hydroxyproline (HYP) in lung tissue homogenate. Results: After the rats were exposed to dust, the dynamic dusting group and the tracheal perfusion group varied significantly in lung histopathology at four time points, and alveolar inflammation and Pulmonary fibrosis scores were higher than the control group ( P <0.05) ; The percentage of type I and type III collagen fiber area of tracheal perfusion group was higher than that in the dynamic dusting group in the four time points ( P <0.05) ; The content of TGF-β1 in lung tissue homogenate of rats in the tracheal perfusion group was higher than that in the dynamic dusting group on the day 3 and 14 ( P <0.05) ; The content of Hyp in the tracheal perfusion group was higher than that in the dynamic dusting group on the day 28 ( P <0.05) . Conclusion: The acute lung injury of rats can be caused by dynamic dusting group and tracheal perfusion group. The lung histopathology shows inflammation and fibrosis, but the lung tissue injury of rats is more serious and the pathological changes are more obvious.

Background: The present study aimed to explore the effectiveness of electro-acupuncture (EA) in combination with a local anesthetic used in Western medicine in preventing the side effects of gastroscopy., Methods: A sample group of 150 patients were divided into three groups based on treatment methods: an EA group, a dyclonine hydrochloride mucilage group, and a combined treatment group. In the EA group, EA stimulation was given at the Hegu, Neiguan, and Zusanli acupoints; in the dyclonine hydrochloride mucilage group, patients took 10 mL of dyclonine hydrochloride mucilage orally; in the combined treatment group, prevention of side effects was attempted by administration of both acupuncture and oral local anesthetic. The incidences of nausea, emesis, salivation, cough, restlessness, and breath holding during gastroscopy were observed and recorded for the three groups. Mean arterial pressure, heart rate, and oxygen saturation were recorded before the examination, and changes in these measures were recorded as the gastroscope passed through the pylorus and after the examination. The visual analogue scale (VAS) values of nausea and emesis, the rate of successful first-pass intubation, and the time of gastroscopy were also recorded. Statistical analysis was performed using R-3.5.3 software., Results: Incidences of side effects (e.g., nausea, emesis, salivation, restlessness, and breath holding) during the examination were lower in the combined treatment group than in the EA group and the dyclonine hydrochloride mucilage group (P<0.05 and P<0.01, respectively). Furthermore, the changes in heart rate and oxygen saturation when the gastroscope passed through the pylorus and after the examination were better in the combined treatment group than in the EA group and dyclonine hydrochloride mucilage group (P<0.01). The VAS values of nausea and emesis, the first-pass success rate, and examination duration were also better for the combined treatment group than for the other two groups (P<0.05 and P<0.01)., Conclusions: EA combined with local anesthesia with dyclonine hydrochloride mucilage can alleviate side effects during gastroscopy, reduce patient pain, and improve the efficiency of the procedure.

A single-shot fluorescence lifetime imaging (FLIM) method based on the compressed ultrafast photography (CUP) is proposed, named space-restricted CUP (srCUP). srCUP is suitable for imaging objects moving slowly (<∼150/ M m m / s , M is the magnification of the objective lens) in the field of view with the intensity changing within nanoseconds in a measurement window around 10 ns. We used synthetic datasets to explore the performances of srCUP compared with CUP and TCUP (a variant of CUP). srCUP not only provides superior reconstruction performances, but its reconstruction speed is also twofold and threefold faster than CUP and TCUP, respectively. The lifetime determination performances were assessed by estimating lifetime components, amplitude- and intensity-weighted average lifetimes ( τ A and τ I ), with the reconstructed scenes using the least squares method based on a bi-exponential model. srCUP has the best accuracy and precision for lifetime determinations with a relative bias less than 7% and a coefficient of variation less than 7% for τ A , and a relative bias less than 10% and a coefficient of variation less than 11% for τ I .

Salinity is one of the most serious factors limiting plant growth which can provoke significant losses in agricultural crop production, particularly in arid and semi-arid areas. This study aimed to investigate whether melatonin (MT; 0.05 and 0.1 mM), which has pleiotropic roles, has a better effect than glycine betaine (GB; 10 and 50 mM) on providing salt tolerance in a woody plant Dalbergia odorifera T. Chen. Also, the alternative oxidase activity (AOX) in plant subjected to MT or GB under salinity (150 and 250 mM) was evaluated given that the effect of exogenous MT or GB on AOX has not been reported yet. The results showed that the exogenous application of GB on the seedlings of D. odorifera increased the plant growth parameters, relative water content, total of chlorophyll content, and carotenoid content compared with well-watered and MT treatments. Under severe salinity, the seedlings subjected to GB showed, a significant enhancement in water use efficiency, transpiration, and net photosynthetic rate regardless to MT-treated seedlings. The levels of proline and soluble sugar in the seedlings treated with MT or GB decreased significantly under mild and severe salinity correlated with those in salt-stressed seedlings. Furthermore, GB-treated plants exhibited a significant inhibition of malondialdehyde content compared with MT-treated plants. The concentration of thiols and phenolic compounds were significantly enhanced in the leaves of seedlings treated with MT compared with those treated with GB. Under salt stress condition, GB scavenged significantly higher levels of hydrogen peroxide than MT; while under severe salinity, plants subjected to MT showed better scavenging ability for hydroxyl radicals compared with GB-treated seedlings. The results demonstrated also an enhancement of the levels of superoxide dismutase (SOD), guaiacol peroxidase, and AOX activities in seedlings treated with GB or MT compared with salt-stressed plants. The catalase activity (CAT) was increased by 0.05 mM MT and 0.1 mM GB under mild salinity. Meanwhile, the AOX activity under severe salinity was enhanced only by GB 50 mM. The findings of this study suggested that GB-treated seedlings possessed a better salt tolerance in comparison with MT-treated seedlings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cisse, Miao, Yang, Huang, Li and Zhang.)

The exploitation of efficient hydrogen evolution reaction (HER) electrocatalysts has become increasingly urgent and imperative; however, it is also challenging for high-performance sustainable clean energy applications. Herein, novel Co 9 S 8 nanoparticles embedded in a porous N,S-dual doped carbon composite (abbr. Co 9 S 8 @NS-C-900) were fabricated by the pyrolysis of a single crystal Co-MOF assisted with thiourea. Due to the synergistic benefit of combining Co 9 S 8 nanoparticles with N,S-dual doped carbon, the composite showed efficient HER electrocatalytic activities and long-term durability in an alkaline solution. It shows a small overpotential of -86.4 mV at a current density of 10.0 mA cm -2 , a small Tafel slope of 81.1 mV dec -1 , and a large exchange current density ( J 0 ) of 0.40 mA cm -2 , which are comparable to those of Pt/C. More importantly, due to the protection of Co 9 S 8 nanoparticles by the N,S-dual doped carbon shell, the Co 9 S 8 @NS-C-900 catalyst displays excellent long-term durability. There is almost no decay in HER activities after 1000 potential cycles or it retains 99.5% of the initial current after 48 h., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Cyp26a1 had important roles in mouse embryo implantation and was highly expressed in some of NK cells at the human maternal-foetal interface in early pregnancy. However, the regulatory effect of Cyp26a1 on NK cells remains poorly understood. Through qPCR and flow cytometric assays, we found that Cyp26a1 was expressed by mouse uterine NK cells but not spleen NK cells during the peri-implantation period and there was a group of NK cells that highly expressed Cyp26a1, that is Cyp26a1 + NK cell subset. single cell-population transcriptome sequencing on Cyp26a1 + NK and Cyp26a1 - NK cell subsets was performed. We found that there were 3957 differentially expressed genes in the Cyp26a1 + NK cell subset with a cut-off of fold change ≥2 and FDR < 0.01, 2509 genes were up-regulated and 1448 genes were down-regulated in Cyp26a1 + NK cell subset. Moreover, cytokine-cytokine receptor interaction signalling pathway and natural killer cell-mediated cytotoxicity signalling pathway were enriched according to KEGG pathway enrichment analysis. We further found that the expression of Gzma and Klrg1 was significantly increased and Fcgr4 was significantly decreased when inhibiting Cyp26a1. Our experimental results show that there is a novel NK cell subset of Cyp26a1 + NK cells in mouse uterus and Cyp26a1 can regulate the gene expression of Gzma, Klrg1 and Fcgr4 in the Cyp26a1 + NK cells., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Infections are the second major cause of mortality in patients with kidney disease and accompanying uremia. Both vascular access and non-access-related infections contribute equally to the infection-related deaths in patients with kidney disease. Dialysis is the most common cause of systemic infection by Candida albicans in these patients. C albicans also reside in the gastrointestinal tract as a commensal fungus. However, the contribution of gut-derived C albicans in non-access-related infections in kidney disease is unknown. Using a mouse model of kidney disease, we demonstrate that uremic animals showed increased gut barrier permeability, impaired mucosal defense, and dysbiosis. The disturbance in gut homeostasis is sufficient to drive the translocation of microbiota and intestinal pathogen Citrobacter rodentium to extraintestinal sites but not C albicans Interestingly, a majority of uremic animals showed fungal translocation only when the gut barrier integrity is disrupted. Our data demonstrate that uremia coupled with gut mucosal damage may aid in the translocation of C. albicans and cause systemic infection in kidney disease. Because most of the individuals with kidney disease suffer from some form of gut mucosal damage, these results have important implications in the risk stratification and control of non-access-related opportunistic fungal infections in these patients., (Copyright © 2021 The Authors.)

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused millions of infections and deaths worldwide since its emergence in December 2019. As there is little or no natural immunity in the human population or specific anti-COVID-19 drugs, researchers from the government, academia and industry are developing vaccines at an unprecedented speed to halt the pandemic. In this review, the results of animal experiments and clinical trials on several vaccine technical platforms are summarized, and several challenges are also discussed to further promote the development, evaluation and application of vaccines during the challenging situation of the global pandemic.

Hypochlorite, as one of reactive oxygen species, has drawn much attention due to its essential roles in special biological events and disorders. The exogenous hypochlorite remains a risk for human, animals and plants. In this work, a novel water soluble quinolin-containing nitrone derivative T has been developed for fluorometric sensing hypochlorite. The response mechanism of T towards ClO - was reported for the first time. In comparison with the reported sensors for ClO - , the sensor T in this work exhibited advantages including high selectivity (80 fold over other analytes), rapid response (within 5 s) and lipid-water distribution transformation (LogP from 2.979 to 6.131). Further biological applications suggested that T was capable of monitoring both exogenous and endogenous ClO - in living cells. The imaging in Arabidopsis thaliana indicated that the absorption and transmission of ClO - in plant could be monitored by this sensor through the chlorine-related mechanism. This work might raise referable information for further investigations in the physiological and pathological events in both tumor and plants., Competing Interests: Declaration of competing interest All authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Berberine (BBR), a kind of quaternary ammonium benzylisoquinoline alkaloids with multiple pharmacological activities, has been regarded as a promising lipid-lowering agent in the field of drug repurposing. Particularly, the chemical modification at the C-9 position of BBR can remarkably improve its lipid-lowering efficacy. In this study, thirteen novel BBR derivatives were rationally designed, synthesized, and evaluated by preliminary pharmacological tests. The results showed that most compounds exhibited more potent hypolipidemic activities when compared with BBR and simvastatin. Among these compounds, compound 2h-1 and 2h-2 exhibited better activity profiling in these four tests involving with inhibition of total cholesterol (TCHO), triglyceride (TG), and low-density lipoprotein cholesterol (LDLC) and the increase of high-density lipoprotein cholesterol (HDLC). Correspondingly, the BBR analogs with 9-O-cinnamic moiety probably exhibited potent lipid-lowering activity, and should be exploited as an important versatile template for the development of BBR-like lipid-lowering agents.

The compressive ultrafast photography (CUP) has achieved real-time femtosecond imaging based on the compressive-sensing methods. However, the reconstruction performance usually suffers from artifacts brought by strong noise, aberration, and distortion, which prevents its applications. We propose a deep compressive ultrafast photography (DeepCUP) method. Various numerical simulations have been demonstrated on both the MNIST and UCF-101 datasets and compared with other state-of-the-art algorithms. The result shows that our DeepCUP has a superior performance in both PSNR and SSIM compared to previous compressed-sensing methods. We also illustrate the outstanding performance of the proposed method under system errors and noise in comparison to other methods.

Although multiple drugs are accessible for recovering liver function in patients, none are considered efficient. Liver transplantation is the mainstay therapy for end-stage liver fibrosis. However, the worldwide shortage of healthy liver donors, organ rejection, complex surgery, and high costs are prompting researchers to develop novel approaches to deal with the overwhelming liver fibrosis cases. Mesenchymal stem cell (MSC) therapy is an emerging alternative method for treating patients with liver fibrosis. However, many aspects of this therapy remain unclear, such as the efficiency compared to conventional treatment, the ideal MSC sources, and the most effective way to use it. Because bone marrow (BM) is the largest source for MSCs, this paper used a systematic review approach to study the therapeutic efficiency of MSCs against liver fibrosis and related factors. We systematically searched multiple published articles to identify studies involving liver fibrosis and BM-MSC-based therapy. Analyzing the selected studies showed that compared with conventional treatment BM-MSC therapy may be more efficient for liver fibrosis in some cases. In contrast, the cotreatment presented a more efficient way. Nevertheless, BM-MSCs are lacking as a therapy for liver fibrosis; thus, this paper also reviews factors that affect BM-MSC efficiency, such as the implementation routes and strategies employed to enhance the potential in alleviating liver fibrosis. Ultimately, our review summarizes the recent advances in the BM-MSC therapy for liver fibrosis. It is grounded in recent developments underlying the efficiency of BM-MSCs as therapy, focusing on the preclinical in vivo experiments, and comparing to other treatments or sources and the strategies used to enhance its potential while mentioning the research gaps., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

This paper aimed to research the function and in-depth mechanism of GPR37 in lung adenocarcinoma (LUAD). Herein, based on TCGA and Oncomine databases, we revealed that GPR37 was expressed at high levels in LUAD, and upregulation of GPR37 was related to the poor outcomes. Furthermore, biological function experiments in vitro were utilized to assess whether GPR37 impacts malignant phenotype of LUAD cells. Gain- or loss-of-function assays indicated that the upregulation of GPR37 contributed to improving the proliferation, migration, and invasion of LUAD cells in vitro , while knockdown of GPR37 can inhibit the malignant biological behaviors. Then, we found that depletion of GPR37 resulted in a decrease in the expression of TGF-β1 as well as the extents of Smad2 and Smad3 phosphorylation, while overexpression of GPR37 presented opposite outcomes. Altogether, our findings indicated that GPR37 is a potential oncogene of LUAD, and its promoting effects on the malignant progression of LUAD may be realized via TGF-β/Smad pathway., Competing Interests: Conflict of interest: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2021 Jian Wang et al., published by De Gruyter.)

Commensal fungi are an important part of human microbial community, among which Candida albicans and Candida glabrata are two common opportunistic pathogens. Unlike the high pathogenicity of C. albicans, C. glabrata is reported to show low pathogenicity to the host. Here, by using a Galleria mellonella infection model, we were able to confirm the much lower virulence of C. glabrata than C. albicans . Interestingly, pre-exposure to live C. glabrata (LCG) protects the larvae against subsequent various lethal fungal infections, including C. albicans, Candida tropicalis, and Cryptococcus neoformans . Inconsistently, heat-inactivated C. glabrata (HICG) pre-exposure can only protect against C. albicans or C. tropicalis re-infection, but not C. neoformans . Mechanistically, LCG or HICG pre-exposure enhanced the fungicidal activity of hemocytes against C. albicans or C. tropicalis . Meanwhile, LCG pre-exposure enhanced the humoral immunity by modulating the expression of fungal defending proteins in the cell-free hemolymph, which may contribute to the protection against C. neoformans . Together, this study suggests the important role of C. glabrata in enhancing host immunity, and demonstrates the great potential of G. mellonella model in studying the innate immune responses against infections.

During the course of evolution of land plants, different classes of flavonoids, including flavonols and anthocyanins, sequentially emerged, facilitating adaptation to the harsh terrestrial environment. Flavanone 3β-hydroxylase (F3H), an enzyme functioning in flavonol and anthocyanin biosynthesis and a member of the 2-oxoglutarate-dependent dioxygenase (2-ODD) family, catalyzes the hydroxylation of ( 2S )-flavanones to dihydroflavonols, but its origin and evolution remain elusive. Here, we demonstrate that functional flavone synthase Is (FNS Is) are widely distributed in the primitive land plants liverworts and evolutionarily connected to seed plant F3Hs. We identified and characterized a set of 2-ODD enzymes from several liverwort species and plants in various evolutionary clades of the plant kingdom. The bifunctional enzyme FNS I/F2H emerged in liverworts, and FNS I/F3H evolved in Physcomitrium ( Physcomitrella ) patens and Selaginella moellendorffii , suggesting that they represent the functional transition forms between canonical FNS Is and F3Hs. The functional transition from FNS Is to F3Hs provides a molecular basis for the chemical evolution of flavones to flavonols and anthocyanins, which contributes to the acquisition of a broader spectrum of flavonoids in seed plants and facilitates their adaptation to the terrestrial ecosystem., (© 2020 American Society of Plant Biologists. All Rights Reserved.)

In insects, 20-hydroxyecdysone (20E) and insulin-like growth factor-like peptides (IGFLPs) regulate the development of imaginal discs. However, how IGFLPs are up-regulated to impact the development of the pupal wing disc is still unclear. In this study, we investigated the expression regulation of IGFLP in the pupal wing disc of silkworm, Bombyx mori. We confirmed that B. mori IGFLP (BmIGFLP) was mainly expressed in the pupal wing disc and the expression of BmIGFLP could be significantly induced by 20E. Bioinformatics analysis of BmIGFLP promoter sequence revealed three cis-regulation elements (CREs) of signal transducer and activator of transcription (STAT), which is a key component in the Janus-activated kinase / STAT pathway. Luciferase activity assays showed that two CREs enhanced the transcriptional activity of BmIGFLP. Electrophoretic mobility shift and chromatin immunoprecipitation assays demonstrated that BmSTAT proteins in the nuclear extracts of B. mori pupal wing discs and BmN cells could only bind to the STAT CRE3, indicating that STAT CRE3 activated by BmSTAT enhances BmIGFLP expression at pupal stages. Although 20E could not enhance the expression of BmSTAT, 20E enhanced the nucleus translocation of BmSTAT to bind with the STAT CRE3 in the BmIGFLP promoter. The increase of transcriptional activity of the STAT CRE3 by overexpression of BmSTAT and addition of 20E in BmN cells confirmed this result. Taken together, all data indicate that BmSTAT is one of the transcription factors activating 20E-induced BmIGFLP expression in the pupal wing disc., (© 2019 Institute of Zoology, Chinese Academy of Sciences.)

Recent studies have demonstrated a marked decrease in peripheral lymphocyte levels in patients with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Few studies have focused on the changes of NK, T- and B-cell subsets, inflammatory cytokines and virus-specific antibodies in patients with moderate COVID-19. A total of 11 RT-PCR-confirmed convalescent patients with COVID-19 and 11 patients with non-SARS-CoV-2 pneumonia (control patients) were enrolled in this study. NK, CD8 + T, CD4 + T, Tfh-like and B-cell subsets were analysed using flow cytometry. Cytokines and SARS-CoV-2-specific antibodies were analysed using an electrochemiluminescence immunoassay. NK cell counts were significantly higher in patients with COVID-19 than in control patients (P = 0.017). Effector memory CD8 + T-cell counts significantly increased in patients with COVID-19 during a convalescent period of 1 week (P = 0.041). TIM-3 + Tfh-like cell and CD226 + Tfh-like cell counts significantly increased (P = 0.027) and decreased (P = 0.022), respectively, during the same period. Moreover, ICOS + Tfh-like cell counts tended to decrease (P = 0.074). No abnormal increase in cytokine levels was observed. The high expression of NK cells is important in innate immune response against SARS-CoV-2. The increase in effector memory CD8 + T-cell counts, the up-regulation of inhibitory molecules and the down-regulation of active molecules on CD4 + T cells and Tfh-like cells in patients with COVID-19 would benefit the maintenance of balanced cellular and humoural immune responses, may prevent the development of severe cases and contribute to the recovery of patients with COVID-19., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Berberine (BBR), a well-known alkaloid, exhibits various pharmacological activities, especially hypolipidemic activity, which has attracted much interest from medicinal chemists in the past decade. However, little progress was made on the structural modification of BBR for improving lipid-lowering activity, mainly due to its unclear biological target and low safety. In this study, a new scaffold of 7,9-disulfatetrahydroberberine was discovered unexpectedly, provided with extremely low cytotoxicity. Hence, a novel series of highly safe 7,9-disulfatetrahydroberberines were designed, synthesized, and evaluated for their hypolipidemic activities. In order to investigate the significance of the 9-position substituent, another new series of 7-sulfatetrahydroberberines were designed and synthesized. Lipid-lowering experiments showed that among these compounds, 5f exhibited the best lipid-lowering activity based on two cell models, 3T3-L1 cells and HepG2 cells. Compared with the blank control, the inhibition rate of compound 5f against total cholesterol was over 60%, the inhibition rate against triglyceride was over 70%, the inhibition rate against low-density lipoprotein cholesterol was approximately 75%, and the inhibition rate against high-density lipoprotein cholesterol was close to 50%, which were far superior to the positive control BBR. This result also verified the feasibility of the development of BBR as a lipid-lowering drug via disubstituted modification at the 7- and 9-position., Competing Interests: The authors declare no competing financial interest., (© 2020 American Chemical Society.)

Background: Systematic investigation and analysis of cardiovascular health status (CVHS) of Chinese women is rare. This study aimed to assess CVHS and atherosclerotic cardiovascular disease (ASCVD) burden in the Chinese women physicians (CWP) and community-based non-physician cohort (NPC)., Methods: In this prospective, multicenter, observational study, CVHS using the American Heart Association (AHA) defined 7 metrics (such as smoking and fasting glucose) and ASCVD risk factors including hypertension, hyperlipidemia and type-2 diabetes were evaluated in CWP compared with NPC., Results: Of 5832 CWP with a mean age of 44 ± 7 years, only 1.2% achieved the ideal CVHS and 90.1% showed at least 1 of the 7 AHA CVHS metrics at a poor level. Total CVHS score was significantly decreased and ASCVD risk burden was increased in postmenopausal subjects in CWP although ideal CVHS was not significantly influenced by menopause. Compared to 2596 NPC, fewer CWP had ≥ 2 risk factors (8% vs. 27%, P < 0.001); CWP scored significantly higher on healthy factors, a composite of total cholesterol, blood pressure, fasting glucose (P < 0.001), but, poorly on healthy behaviors (P < 0.001), specifically in the physical activity component; CWP also showed significantly higher levels of awareness and rates of treatment for hypertension and hyperlipidemia, but, not for type-2 diabetes., Conclusion: Chinese women's cardiovascular health is far from ideal and risk intervention is sub-optimal. Women physicians had lower ASCVD burden, scored higher in healthy factors, but, took part in less physical activity than the non-physician cohort. These results call for population-specific early and improved risk intervention.

Toxic effectors secreted by the type VI secretion system (T6SS) facilitate interbacterial warfare, as well as pathogenesis toward humans, animals and plants. However, systematically predicting T6SS effectors remains challenging due to their sequence and functional diversity. In this study, we systematically identified putative T6SS toxic effectors in prokaryotic genomes on the basis of the observation that genes encoding adaptor proteins and genes encoding cognate effector proteins are generally adjacent in the genome. Adaptor proteins are mediators that help to load their cognate effectors onto the T6SS spike complex. The contextual genes of the known adaptor proteins (DUF1795, DUF2169 or DUF4123) all exhibited a high proportion of encoding T6SS spike complex protein (VgrG or PAAR) and effector proteins. On the basis of the genomic context, we found that PRK06147 might be a novel adaptor protein. These four adaptors are widely distributed among the bacterial genomes. From neighbors of 5297 adaptor genes, we identified 1356 putative effector genes from 92 different families, and two-thirds were currently annotated as hypothetical proteins or as having unknown functions. Our results indicate that each class of adaptors can be used as an effective marker to identify T6SS toxic effectors, moreover, this approach can promote the discovery of new effectors., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Author(s).)

Key Message: EgMADS21 regulates PUFA accumulation in oil palm. Oil palm (Elaeis guineensis Jacq.) is the most productive world oil crop, accounting for 36% of world plant oil production. However, the molecular mechanism of the transcriptional regulation of fatty acid accumulation and lipid synthesis in the mesocarp of oil palm by up- or downregulating the expression of genes involved in related pathways remains largely unknown. Here, an oil palm MADS-box gene, EgMADS21, was screened in a yeast one-hybrid assay using the EgDGAT2 promoter sequence as bait. EgMADS21 is preferentially expressed in early mesocarp developmental stages in oil palm fruit and presents a negative correlation with EgDGAT2 expression. The direct binding of EgMADS21 to the EgDGAT2 promoter was confirmed by electrophoretic mobility shift assay. Subsequently, transient expression of EgMADS21 in oil palm protoplasts revealed that EgMADS21 not only binds to the EgDGAT2 promoter but also negatively regulates the expression of EgDGAT2. Furthermore, EgMADS21 was stably overexpressed in transgenic oil palm embryoids by Agrobacterium-mediated transformation. In three independent transgenic lines, EgDGAT2 expression was significantly suppressed by the expression of EgMADS21. The content of linoleic acid (C18:2) in the three transgenic embryoids was significantly decreased, while that of oleic acid (C18:1) was significantly increased. Combined with the substrate preference of EgDGAT2 identified in previous research, the results demonstrate the molecular mechanism by which EgMADS21 regulates EgDGAT2 expression and ultimately affects fatty acid accumulation in the mesocarp of oil palm.

Substantial advance supports that CMTM2 serve as an important performer in physiological and pathological processes. However, very little is clear about the relationship between CMTM2 and HBV-related disorders. Here, for the first time, we explore that whether or not serum CMTM2 is involved in HBV-related diseases. We found that CMTM2 values were significantly lower in patients compared to healthy control (p <0.001), using ELISA assay. Furthermore, serum CMTM2 levels were negatively correlated with HBV DNA levels in CHB patients but not correlated with the serum levels of ALT and AST. Serum CMTM2 concentrations were not correlated with the serum levels of ALT, AST and HBV DNA load in HBLC and HCC patients. In addition, analysis of the ROC curve indicated that CMTM2 levels were significantly associated with the diagnostic value of HBV-related disorders. Finally, downregulation of CMTM2 was observed in HBV-infected cell model. CMTM2 degradation could be attributed to HBx-activated Lys48 (K48)-linked polyubiquitination, which was abolished by treatment with the proteasome inhibitor MG132. HBV infection suppresses CMTM2 expression by activating ubiquitin-proteasome system. Serum CMTM2 levels can be adopted as an effective indicator of the pathogenesis of HBV-related disorders., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Shu Chen et al.)

This paper deals with the detailed morphological observation of larva, protonymph and deutonymph, as well as female and male adults of Neoseiulus californicus (McGregor) based on laboratory reared specimens. The main changes are as follows: larva with one dorsal shield, while protonymph with two, which fused into a holodorsal shield in deutonymph; 9 pairs of dorsal setae in larvae, 14 pairs in protonymph, and 19 pairs in deutonymph and adult; the immature stages without discernible ventrianal shield, though hypoplastic shield, a weakly sclerotized small plate around the anal pore, present in the protonymph and deutonymph. larva and protonymph each with seven pairs of ventral setae, while deutonymph and adult each with 12 pairs; movable digit with one or two teeth in larva, three teeth in protonymph, deutonymph or adult. The development of morphological traits in ontogenesis of N. californicus could provide helpful basis to identify it practically from its relatives.

In recent years, the Chinese government has proposed a policy to replace coal use with natural gas and electricity in the northern region to reduce the air pollution caused by the large consumption of coal. In order to assess the air pollution reduction effect of the coal substitution policy in Liaoning Province, this paper proposes a data grouping grey model with a fractional order accumulation (FDGGM (1,1)). The empirical analysis results show that the new grey model can predict the monthly coal consumption more accurately than the traditional DGGM (1,1) model. The MAPEs of the training set in the FDGGM(1,1) and DGGM(1,1) models are 4.58% and 5.48%, and the MAPEs of the test set are 23.89% and 33.78%, respectively. And the policy achieves a great success based on the FDGGM(1,1) model. During the policy implementation period (from January 2015 to December 2018), the coal consumption in Liaoning Province decreased by 27.2501 million tons, while the emissions of CO 2 , SO 2 and NO x fell by 0.714, 0.2316 and 0.2017 million tons, respectively. The results also provide a necessary support to the further implementation of the coal substitution policy.

Background: Identification of novel Ure inhibitors with high potency has received considerable attention. Methodology & results: Ure inhibition was determined using the indophenol method, the affinities to Ure were estimated via surface plasmon resonance. Seventeen new plus ten known N -monosubstituted thiosemicarbazides were synthesized and identified as novel Ure inhibitors. Out of these compounds, compound b5 shows excellent activity against both crude Ure from Helicobacter pylori (IC 50  = 0.04 μM) and Ure in living cell (IC 50  = 0.27 μM), with the potency being over 600-fold higher than clinical used drug acetohyroxamic acid, respectively. Surface plasmon resonance demonstrated the high affinity ( K d .#x00A0;= 6.32 nM) of b5 to Ure. Conclusion: This work provides a class of novel and promising Ure inhibitors.

Acetylation and deacetylation of histones are important for regulating a series of biological processes in plants. Histone deacetylases (HDACs) control the histone deacetylation that plays an important role in plant response to abiotic stress. In our study, we show the evidence that GhHDT4D (a member of the HD2 subfamily of HDACs) is involved in cotton (Gossypium hirsutum) response to drought stress. Overexpression of GhHDT4D in Arabidopsis increased plant tolerance to drought, whereas silencing GhHDT4D in cotton resulted in plant sensitivity to drought. Simultaneously, the H3K9 acetylation level was altered in the GhHDT4D silenced cotton, compared with the controls. Further study revealed that GhHDT4D suppressed the transcription of GhWRKY33, which plays a negative role in cotton defense to drought, by reducing its H3K9 acetylation level. The expressions of the stress-related genes, such as GhDREB2A, GhDREB2C, GhSOS2, GhRD20-1, GhRD20-2 and GhRD29A, were significantly decreased in the GhHDT4D silenced cotton, but increased in the GhWRKY33 silenced cotton. Given these data together, our findings suggested that GhHDT4D may enhance drought tolerance by suppressing the expression of GhWRKY33, thereby activating the downstream drought response genes in cotton.

The aim of this study was to determine the seroprevalence of Babesia caballi and Theileria equi in horses imported into Shanghai port. Between 2018 and 2019, 344 horse sera samples were collected and tested for B. caballi and T. equi, using commercially available kits. Only one B. caballi seropositive sample was detected. To the best of our knowledge, this is the first report of a B. caballi seropositive in imported horses at Shanghai port, which reflects the importance of monitoring piroplasmosis seroprevalence in imported horses., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Developing green and sustainable Pickering interfacial catalysts for organic reactions in water is of great importance to both the environment and human health. In this study, Janus-type amphiphilic cellulose nanocrystals (CNCs) were synthesized by the surface modification of hydrophilic CNCs with hydrophobic alkyl chains for efficient Pickering emulsion stabilization. Further deposition of palladium nanoparticles on amphiphilic CNCs provides catalytic activity for organic reactions in water, which occur at the interface of water and the organic reactant phase. Different reactions, hydrogenation and C-C coupling, were performed using the obtained Pickering interfacial catalyst. Excellent results were achieved in both reactions. The catalyst developed in our study is expected to advance the field of environment-friendly catalyst systems for green chemistry.

Objective: To investigate the efficacy and safety of emergency venous sinus stenting in the treatment of acute visual impairment caused by idiopathic intracranial hypertension (IIH). Methods: A descriptive cross-sectional study design was used to retrospectively analyze 38 patients undergoing venous sinus stenting in the First Affiliated Hospital of Zhengzhou University from January 2013 to October 2019. A total of 9 patients who had sudden short-term vision loss met the inclusion criteria. Routine visual field and fundus examination were performed. The venous sinus stenosis (CVSS) was confirmed by MR venography or DSA. The pressure gradient at both ends of CVSS was ≥10 mmHg(1 mmHg=0.133 kPa). All patients were treated with emergency venous sinus stenting. Six-month follow-up data were collected for comparison, evaluation of the therapeutic effect, and observation of adverse reactions. Results: All 9 patients were successfully treated with venous sinus stent. The pressure gradient at the distal and proximal ends of the stenosis after stent implantation decreased to (2.3±1.2) mmHg. After 6 months of follow-up, the papilledema was significantly improved or disappeared in all patients. The average grade of papilledema decreased from 2.44±0.73 before operation to 0.56±0.53 after treatment ( t= 6.314, P< 0.001). The visual acuity of 9 patients recovered to the pre-onset level or improved significantly after 6 months. The average baseline value of preoperative visual acuity (logMAR) was 0.12±0.11, which increased to 0.74±0.13 on average 6 months after operation ( t= -10.827, P< 0.001). No recurrence of symptoms or serious adverse reactions occurred in all patients during the follow-up period. Conclusion: For patients with acute visual impairment caused by idiopathic cranial hypertension, emergency venous sinus stenting is a relatively safe and effective treatment that can effectively improve visual acuity.

Parkinson's disease (PD) is the second most prevalent central nervous system (CNS) degenerative disease. Oxidative stress is one of key contributors to PD. Nuclear factor erythroid-2-related factor 2 (Nrf2) is considered to be a master regulator of many genes involved in anti-oxidant stress to attenuate cell death. Therefore, activation of Nrf2 signalling provides an effective avenue to treat PD. Ellagic acid (EA), a natural polyphenolic contained in fruits and nuts, possesses amounts of pharmacological activities, such as anti-oxidant stress and anti-inflammation. Recent studies have confirmed EA could be used as a neuroprotective agent in neurodegenerative diseases. Here, mice subcutaneous injection of rotenone (ROT)-induced DA neuronal damage was performed to investigate EA-mediated neuroprotection. In addition, adult Nrf2 knockout mice and different cell cultures including MN9D-enciched, MN9D-BV-2 and MN9D-C6 cell co-cultures were applied to explore the underlying mechanisms. Results demonstrated EA conferred neuroprotection against ROT-induced DA neurotoxicity. Activation of Nrf2 signalling was involved in EA-mediated DA neuroprotection, as evidenced by the following observations. First, EA activated Nrf2 signalling in ROT-induced DA neuronal damage. Second, EA generated neuroprotection with the presence of astroglia and silence of Nrf2 in astroglia abolished EA-mediated neuroprotection. Third, EA failed to produce DA neuroprotection in Nrf2 knockout mice. In conclusion, this study identified EA protected against DA neuronal loss via an Nrf2-dependent manner., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Allergic rhinitis (AR) is a nasal mucosal inflammatory disease mediated by environmental allergens. At present, the relationship between the IL-33/ST2 axis, ERK1/2 pathway and AR progression needs further exploration. In our study, an AR model was constructed in vitro by treating HNEpC cells with Der p1. qRT-PCR was applied to assess the mRNA levels of IL-33, ST2, TNF-α, IL-6, and IL-8. Western blotting was used to measure the protein levels of IL-33, ST2, and the downstream proteins p-ERK1/2, ERK1/2, p-RSK, and RSK. IL-6, IL-8, IL-33, and TNF-α protein levels in cell supernatants were evaluated by ELISA. Flow cytometry was performed to check cell apoptosis of HNEpC in the presence or absence of Der p1. Our results indicate that the relative levels of IL-33, ST2, TNF-α, IL-6, and IL-8 were increased significantly in the AR model group. The above effects were notably reversed after transfection with shIL-33 or shST2. IL-33 stimulation further resulted in the increase in both ST2 and inflammation-associated cytokines, and these effects were restored after shST2 treatment. Also, the levels of inflammatory factors induced by IL-33 stimulation or ST2 overexpression were reversed after applying an ERK1/2 pathway blocker. In conclusion, IL-33/ST2 mediated inflammation of nasal mucosal epithelial cells by inducing the ERK1/2 pathway.

Objective: A meta-analysis was conducted on the clinical efficacy and safety of Wenxin granules and propafenone for the therapy of atrial premature beats (APBs)., Methods: A randomized controlled trial (RCT) of Wenxin granules and propafenone in the therapy of APB was systematically searched until June 1, 2019. Meta-analysis was conducted with review manager (RevMan) 5.3. For the evaluation of methodological quality for randomized controlled trials, the Cochrane tool was used to assess the risk of bias. For the evaluation of the evidence quality, the online GRADEpro GDT was used., Results: Eleven RCTs with 1149 participants were included in this study. It has been identified that Wenxin granules combined with propafenone have better clinical efficacy than the use of propafenone alone in the treatment of APB (OR = 3.89, 95% CI (2.03, 7.44), P < 0.0001, low-dose propafenone; OR = 4.24, 95% CI (1.32, 13.60), P = 0.02, high-dose propafenone). There is no difference in clinical efficacy between the Wenxin granules alone and high-dose propafenone in the treatment of APB (OR = 1.17, 95% CI (0.65, 2.11), P = 0.60), and Wenxin granules alone are superior to the low-dose propafenone in the treatment of APB (OR = 2.56, 95% CI (1.34, 4.89), P = 0.004). Wenxin granules combined with propafenone can reduce the incidence of sinus bradycardia caused by propafenone (OR = 0.15, 95% CI (0.03, 0.70), P = 0.02). There was no significant difference between Wenxin granules combined with propafenone and propafenone alone in causing the atrioventricular block, dizziness, xerostomia, gastrointestinal symptoms, and tongue paresthesia. There was no significant difference between Wenxin granules alone and propafenone alone in causing dizziness, xerostomia, gastrointestinal symptoms, tongue paresthesia, frequent premature ventricular contractions, and prolongation of R-R interval., Conclusion: Very low-quality evidence showed that Wenxin granules may be superior to low-dose propafenone in the treatment of APB. Wenxin granules may reduce the incidence of sinus bradycardia caused by propafenone. Limited by the quality of included RCTs, the conclusions of this study still need further verification., Competing Interests: The authors declare that there are no conflicts of interest regarding this study., (Copyright © 2020 Yi Yuan et al.)

Peripheral nerve injury may trigger changes in mRNA levels in the spinal cord. Finding key mRNAs is important for improving repair after nerve injury. This study aimed to investigate changes in mRNAs in the spinal cord following sciatic nerve injury by transcriptomic analysis. The left sciatic nerve denervation model was established in C57BL/6 mice. The left L4-6 spinal cord segment was obtained at 0, 1, 2, 4 and 8 weeks after severing the sciatic nerve. mRNA expression profiles were generated by RNA sequencing. The sequencing results of spinal cord mRNA at 1, 2, 4, and 8 weeks after severing the sciatic nerve were compared with those at 0 weeks by bioinformatic analysis. We identified 1915 differentially expressed mRNAs in the spinal cord, of which 4, 1909, and 2 were differentially expressed at 1, 4, and 8 weeks after sciatic nerve injury, respectively. Sequencing results indicated that the number of differentially expressed mRNAs in the spinal cord was highest at 4 weeks after sciatic nerve injury. These mRNAs were associated with the cellular response to lipid, ATP metabolism, energy coupled proton transmembrane transport, nuclear transcription factor complex, vacuolar proton-transporting V-type ATPase complex, inner mitochondrial membrane protein complex, tau protein binding, NADH dehydrogenase activity and hydrogen ion transmembrane transporter activity. Of these mRNAs, Sgk1, Neurturin and Gpnmb took part in cell growth and development. Pathway analysis showed that these mRNAs were mainly involved in aldosterone-regulated sodium reabsorption, oxidative phosphorylation and collecting duct acid secretion. Functional assessment indicated that these mRNAs were associated with inflammation and cell morphology development. Our findings show that the number and type of spinal cord mRNAs involved in changes at different time points after peripheral nerve injury were different. The number of differentially expressed mRNAs in the spinal cord was highest at 4 weeks after sciatic nerve injury. These results provide reference data for finding new targets for the treatment of peripheral nerve injury, and for further gene therapy studies of peripheral nerve injury and repair. The study procedures were approved by the Ethics Committee of the Peking University People's Hospital (approval No. 2017PHC004) on March 5, 2017., Competing Interests: None

Objective: To analyze the relationship between the distribution of lower limb alignment and short term clinical efficacy in patients with varus-type osteoarthritis after primary total knee arthroplasty (TKA)., Methods: From December 2016 to March 2018, 87 patients (101 knees) with knee osteoarthritis were treated with the first total knee arthroplasty by the same medical group, including 21 males(25 knees) and 66 females(76 knees), ranging in age from 51 to 85 years old, with a mean of (67.6±7.0) years old. According to the difference of hip knee ankle angle (HKA) after total knee arthroplasty, the patients were divided into 4 groups:neutral position group (group A), -3°≤HKA≤3°, 50 knees;slight varus group (group B), 3°< HKA<6°, 20 knees;severe varus group (group C), HKA≥6°, 20 knees;valgus group (group D), HKA<- 3°, 11 knees. The preoperative sex, age, body mass index, operative side, preoperative and postoperative knee joint activity, HSS score, KSS clinical and functional score were compared among the 4 groups, and the relationship between the force line distribution of femoral and tibial prosthesis and the recent clinical effect was compared., Results: All the patients were followed up with a mean duration of(18.4±4.0) months. The range of motion of knee joint, HSS and KSS scores at the latest follow-up after operation in the 4 groups were higher than those before operation, and the difference was statistically significant ( P <0.001). There were significant differences in HSS and KSS scores among the 4 groups at the latest follow up ( P <0.05);and the results in group A were better than those in group C and group D ( P <0.05);the results in group B were better than those in group C and group D ( P < 0.05);there was no significant difference between group A and group B or group C and group D( P >0.05). There was no significant difference in knee joint activity among the 4 groups. The score of femoral prosthesis force line within ±3°was better than that of the other group ( P <0.05), and the score of tibia prosthesis force line had no significant difference between within ±3° group and other group ( P >0.05)., Conclusion: The short term clinical efficacy of patients with knee varus osteoarthritis after primary total knee arthroplasty is related to the distribution of lower limbs alignment. The short-term clinical efficacy of slight inversion position can be similar to that of neutral position. The force line distribution of femoral prosthesis is related to the short term clinical efficacy after primary knee arthroplasty.