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In this work, a photoelectrochemical (PEC) immunosensor was constructed for the ultrasensitive detection of lung cancer marker neuron-specific enolase (NSE) based on a microflower-like heterojunction of cadmium indium sulfide and magnesium indium sulfide (CdIn 2 S 4 /MgIn 2 S 4 , CMIS) as photoactive material. Specifically, the well-matched energy level structure and narrow energy level gradients between CdIn 2 S 4 and MgIn 2 S 4 could accelerate the separation of electron-hole (e - -h + ) pairs in the CMIS heterojunction to enhance the photocurrent of CMIS, which was increased 5.5 and 80 times compared with that of single CdIn 2 S 4 and MgIn 2 S 4 , respectively. Meanwhile, using CMIS as photoactive material, increasing the biocompatibility by dropping Pt NPs on the surface of CMIS to immobilize the antibody through Pt-N bond. Fe 3 O 4 -Ab 2 , acting as the quencher, competitively consumes electron donors and absorbs light, leading to photocurrent quenching. With the increasing of quencher, the photocurrent decreased. Hence, the developed "signal-off" PEC immunosensor realized the trace detection of NSE within the range from 1.0 fg/mL to 10 ng/mL with a low detection limit of 0.34 fg/mL. This strategy provided a new perspective for establishing ternary metal sulfide heterojunction to construct PEC immunosensor for sensitive detection of disease biomarkers., 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 B.V.)

General anesthesia, as a commonly used medical intervention, has been widely applied during surgical procedures to ensure rapid loss of consciousness and pain relief for patients. However, recent research suggests that general anesthesia may be associated with the occurrence of perioperative neurocognitive disorder (PND). PND is characterized by a decline in cognitive function after surgery, including impairments in attention, memory, learning, and executive functions. With the increasing trend of population aging, the burden of PND on patients and society's health and economy is becoming more evident. Currently, the clinical consensus tends to believe that peripheral inflammation is involved in the pathogenesis of PND, providing strong support for further investigating the mechanisms and prevention of PND., 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 © 2024 Li, Li, Fang, Chen, Yu and Zhu.)

Progress in histological methods and in microscope technology has enabled dense staining and imaging of axons over large brain volumes, but tracing axons over such volumes requires new computational tools for 3D reconstruction of data acquired from serial sections. We have developed a computational pipeline for automated tracing and volume assembly of densely stained axons imaged over serial sections, which leverages machine learning-based segmentation to enable stitching and alignment with the axon traces themselves. We validated this segmentation-driven approach to volume assembly and alignment of individual axons over centimeter-scale serial sections and show the application of the output traces for analysis of local orientation and for proofreading over aligned volumes. The pipeline is scalable, and combined with recent advances in experimental approaches, should enable new studies of mesoscale connectivity and function over the whole human brain.

Background: Pseudoachalasia is a rare disease that behaves similarly to achalasia (AC), making it sometimes difficult to differentiate., Case Presentation: We report a case of 49-year-old male with adenocarcinoma of the gastroesophageal junction misdiagnosed as achalasia. No obvious abnormalities were found in his initial examinations including upper digestive endoscopy, upper gastrointestinal imaging and chest computed tomography (CT). During the subsequent introduced-peroral endoscopic myotomy (POEM), it was found that the mucosal layer and the muscular layer had severe adhesion, which did not receive much attention, delayed the clear diagnosis and effect treatment, and ultimately led to a poor prognosis for the patient., Conclusions: This case suggests that when patients with AC found mucosal and muscular adhesions during POEM surgery, the possibility should be considered that the lesion may be caused by a malignant lesion., (© 2024. The Author(s).)

In early sensory systems, cell-type diversity generally increases from the periphery into the brain, resulting in a greater heterogeneity of responses to the same stimuli. Surround suppression is a canonical visual computation that begins within the retina and is found at varying levels across retinal ganglion cell types. Our results show that heterogeneity in the level of surround suppression occurs subcellularly at bipolar cell synapses. Using single-cell electrophysiology and serial block-face scanning electron microscopy, we show that two retinal ganglion cell types exhibit very different levels of surround suppression even though they receive input from the same bipolar cell types. This divergence of the bipolar cell signal occurs through synapse-specific regulation by amacrine cells at the scale of tens of microns. These findings indicate that each synapse of a single bipolar cell can carry a unique visual signal, expanding the number of possible functional channels at the earliest stages of visual processing., (© 2024. The Author(s).)

Objectives: For resectable esophageal cancer, the choice of total minimally invasive esophagectomy (TMIE) or hybrid minimally invasive esophagectomy (HMIE) remains controversial. The purpose of this study was to evaluate the short-term clinical outcomes of TMIE and HMIE under the Ivor-Lewis procedure., Methods: The data of 145 patients diagnosed with middle or lower esophageal cancer who underwent radical Ivor-Lewis esophagectomy in the Affiliated Hospital of Qingdao University between January 2018 and December 2019 were retrospectively analyzed. The short-term outcomes such as complications during surgery or within 30 days after surgery and postoperative pain were analyzed., Results: All patients were divided into TMIE group (75 patients) and HMIE group (70 patients). No significant difference was observed in the baseline characteristics of the two groups. TMIE was associated with less blood loss than the HMIE group (p < 0.05). A total of 54 (37.2%) patients had postoperative complications. Although the two groups were statistically similar in the incidence of major complications, patients in the HMIE group were more likely to have pneumonia compared with those in the TMIE group. The numeric rating scale for pain was significantly higher in the HMIE group (p = 0.002) and more patients required an additional opioid analgesia after esophagectomy (p = 0.282)., Conclusions: In conclusion, according to perioperative outcomes, TMIE can benefit patients better than HMIE., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest, and there is no funding for the work., (Copyright © 2023 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

An efficient strategy for visible-light-promoted decarboxylative alkylation of vinylcyclopropanes with alkyl N -(acyloxy)phthalimide esters through the dual C-C bond and single N-O bond cleavage, employing triphenylphosphine and lithium iodide as the photoredox system to synthesize 2-alkylated 3,4-dihydronaphthalenes, has been established. This alkylation/cyclization involves a radical process and undergoes a sequence of N -(acyloxy)phthalimide ester single-electron reduction, N-O bond cleavage, decarboxylative, alkyl radical addition, C-C bond cleavage, and intramolecular cyclization. Moreover, using the photocatalyst Na 2 -Eosin Y instead of triphenylphosphine and lithium iodide, the vinyl transfer products are acquired when vinylcyclobutanes or vinylcyclopentanes are utilized as alkyl radical receptors.

A visible-light-induced three-component reaction of 2-aryl indoles/benzimidazoles, Hantzsch esters, and sodium pyrosulfite through a radical cascade cyclization process with the insertion of sulfur dioxide is described. It provides a novel and powerful way for the synthesis of alkylsulfonated isoquinolinones. Hantzsch esters and Na 2 S 2 O 5 are employed as alkyl radical precursors and SO 2 surrogate, respectively. This transformation exhibits good functional group tolerance and substrate applicability under mild conditions.

Atherosclerosis, a chief pathogenic factor of cardiovascular disease, is associated with many factors including inflammation, dyslipidemia, and oxidative stress. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors and are widely expressed with tissue- and cell-specificity. They control multiple genes that are involved in lipid metabolism, inflammatory response, and redox homeostasis. Given the diverse biological functions of PPARs, they have been extensively studied since their discovery in 1990s. Although controversies exist, accumulating evidence have demonstrated that PPAR activation attenuates atherosclerosis. Recent advances are valuable for understanding the mechanisms of action of PPAR activation. This article reviews the recent findings, mainly from the year of 2018 to present, including endogenous molecules in regulation of PPARs, roles of PPARs in atherosclerosis by focusing on lipid metabolism, inflammation, and oxidative stress, and synthesized PPAR modulators. This article provides information valuable for researchers in the field of basic cardiovascular research, for pharmacologists that are interested in developing novel PPAR agonists and antagonists with lower side effects as well as for clinicians., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Paenibacillus terrae NK3-4 is a plant growth-promoting rhizobacterium. In this study, the effects of NK3-4 on rice growth and gene transcription were determined. The results indicated that a seed soaking treatment and a pre-germination seed treatment using NK3-4 promoted rice growth, especially spraying rice seedlings with NK3-4 increased the root number and root length by 34.2% and 34.1%, respectively. Moreover, NK3-4 induced the differential transcription of genes annotated with gene ontology (GO) terms; the number of up-regulated genes was 4.38-times higher than the number of down-regulated genes. The NK3-4 treatment induced the differential transcription of genes in 1794 GO functional groups, with 1531 functional groups containing up-regulated genes. Specific growth-related genes up-regulated by NK3-4 are involved in biological processes, including responses to auxin, hormone biosynthesis, cellular component biogenesis, root system development, and other functions. Furthermore, stress resistance-related genes were up-regulated, some of which encode WRKYs, NPK1-related protein kinase, NPR1-like 4, CaM-like proteins, MYBs, ERFs, TIFYs, NACs, EL5s, PR1s, PR2, PR8, PODs, and PAD4. Considered together, these findings imply that NK3-4 may promote plant growth and enhance stress resistance by regulating gene expression, making it a potentially useful microbe for regulating rice growth and stress resistance., Competing Interests: The authors declare that they have no competing interests.

Accumulating evidence has demonstrated that polysaccharides derived from edible fungi have lipid-lowering effects in mice. However, the lipid metabolism mechanisms in mice and humans are different. We have previously elucidated the structural characteristics of the alkali-extracted polysaccharide CM3-SII obtained from Cordyceps militaris. This study aimed to investigate whether CM3-SII could ameliorate hyperlipidemia in a heterozygous low-density lipoprotein receptor (LDLR)-deficient hamster model of hyperlipidemia. Our data demonstrated that CM3-SII significantly decreased total plasma cholesterol, non-high-density lipoprotein cholesterol, and triglyceride levels in heterozygous LDLR-deficient hamsters. Unlike ezetimibe, CM3-SII could enhance the concentration of plasma apolipoprotein A1 and the expression of liver X receptor α/ATP-binding cassette transporter G8 mRNA pathway and suppress the expression of Niemann-Pick C1-like 1, which help to reduce cholesterol levels further. Moreover, the results of molecular docking analysis demonstrated that CM3-SII could directly bind to Niemann-Pick C1-like 1 with high affinity. The triglyceride-lowering mechanisms of CM3-SII were related to its downregulation of sterol regulatory element-binding protein 1c and upregulation of peroxisome proliferator-activated receptor α. Importantly, CM3-SII increased the abundance of Actinobacteria and Faecalibaculum and the ratio of Bacteroidetes/Firmicutes. Thus, CM3-SII attenuated hyperlipidemia by modulating the expression of multiple molecules involved in lipid metabolism and the gut microbiota., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2023. Published by Elsevier B.V.)

Aim: To investigate the thrifty effects of subanesthetic-dose S-ketamine on postoperative opioids and its safety and analgesic efficacy., Methods: Four-hundred and twenty patients were divided into the control group (CON group), the S-ketamine 0.2 mg/kg group (ES0.2 group), and the S-ketamine 0.3 mg/kg group (ES0.3 group) randomly. Major indicators include the Visual Analogue Scale (VAS), the times of compression with analgesic pumps after surgery, and analgesic drug consumption from anesthesia induction to 48 h after surgery. Minor records include vital signs, the use of vasoactive drugs, the Ramsay scores, the occurrence of adverse events including nervous system reaction, and the patient's satisfaction with anesthesia., Results: Compared with the CON group, VAS scores decreased in the ES0.2 and ES0.3 groups ( p  < 0.05). At 10 min after extubation, the VAS scores of the ES0.3 group were lower than that of the ES0.2 group ( p  < 0.05). The total number of compression with analgesic pumps of the ES0.3 group was lower than that of the CON group ( p  < 0.05). The opioid consumption after surgery of the ES0.3 group was lower than those of the CON group and the ES0.2 group ( p  < 0.05). The ES0.3 group's heart rate (HR) was faster but the use of vasoactive, drug consumption was less than the other two groups ( p  < 0.05). There were no significant differences in the incidence of postoperative adverse events and anesthetic satisfaction among the three groups., Conclusion: Subanesthetic-dose S-ketamine at 0.2-0.3 mg/kg especially the 0.3 mg/kg in general anesthesia induction can safely and effectively reduce postoperative pain and save postoperative opioid consumption., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Ibrain published by Affiliated Hospital of Zunyi Medical University and Wiley‐VCH GmbH.)

A total of 10 lactobacillus strains were isolated from broiler chickens and their probiotic properties including tolerance to gastrointestinal fluids and heat treatment, antimicrobial activity, adhesion capacity to intestinal cells, surface hydrophobicity, autoaggregation, antioxidative activity, and immunomodulatory effects on chicken macrophages were evaluated. The Limosilactobacillus reuteri (LR) was the most frequently isolated species, followed by Lactobacillus johnsonii (LJ) and Ligilactobacillus salivarius (LS). All isolates showed good resistance to simulated gastrointestinal conditions and antimicrobial activity against 4 indicator strains including Escherichia coli, Salmonella typhimurium, Klebsiella pneumoniae, and Proteus mirabilis LR 21 exhibited excellent performances on autoaggregation, hydrophobicity and adhesion capacity to Caco-2 intestinal cells. In the meantime, this strain also possessed considerable tolerance to heat treatment, which indicated great potential to be used in the feed industry. However, LJ 20 strain had the highest free radical scavenging activity compared with the other strains. Furthermore, qRT-PCR results revealed that all isolated strains significantly increased the transcriptional levels of proinflammatory genes and tended to induce the M1-type polarization on HD11 macrophages. Particularly, the technique for order preference by similarity to ideal solution (TOPSIS) was adopted in our study to compare and select the most promising probiotic candidate based on in vitro evaluation tests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Ménière's disease, a multifactorial disorder of the inner ear, is characterized by severe vertigo episodes and hearing loss. Although the role of immune responses in Ménière's disease has been proposed, the precise mechanisms remain undefined. Here, we show that downregulation of serum/glucocorticoid-inducible kinase 1 is associated with activation of NLRP3 inflammasome in vestibular-resident macrophage-like cells from Ménière's disease patients. Serum/glucocorticoid-inducible kinase 1 depletion markedly enhances IL-1β production which leads to the damage of inner ear hair cells and vestibular nerve. Mechanistically, serum/glucocorticoid-inducible kinase 1 binds to the PYD domain of NLRP3 and phosphorylates it at Serine 5, thereby interfering inflammasome assembly. Sgk -/- mice show aggravated audiovestibular symptoms and enhanced inflammasome activation in lipopolysaccharide-induced endolymphatic hydrops model, which is ameliorated by blocking NLRP3. Pharmacological inhibition of serum/glucocorticoid-inducible kinase 1 increases the disease severity in vivo. Our studies demonstrate that serum/glucocorticoid-inducible kinase 1 functions as a physiologic inhibitor of NLRP3 inflammasome activation and maintains inner ear immune homeostasis, reciprocally participating in models of Ménière's disease pathogenesis., (© 2023. The Author(s).)

Macrophages are involved in the whole process of atherosclerosis, which is characterized by accumulation of lipid and inflammation. Presently, clinically used lipid-lowering drugs cannot completely retard the progress of atherosclerosis. Liver X receptor (LXR) plays a key role in regulation of lipid metabolism and inflammation. Accumulating evidence have demonstrated that synthetic LXR agonists can significantly retard the development of atherosclerosis. However, these agonists induce sever hypertriglyceridemia and liver steatosis. These side effects have greatly limited their potential application for therapy of atherosclerosis. The rapid development of drug delivery system makes it possible to delivery interested drugs to special organs or cells using nanocarriers. Macrophages express various receptors which can recognize and ingest specially modified nanocarriers loaded with LXR agonists. In the past decades, a great progress has been made in this field. These macrophage-targeted nanocarriers loaded with LXR agonists are found to decrease atherosclerosis by reducing cholesterol accumulation and inflammatory reactions. Of important, these nanocarriers can alleviate side effects of LXR agonists. In this article, we briefly review the roles of macrophages in atherosclerosis, mechanisms of action of LXR agonists, and focus on the advances of macrophage-targeted nanocarriers loaded with LXR agonists. This work may promote the potential clinical application of these nanocarriers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yang, Miao, Yu, Wang, Xia, Li and Guo.)

Neurons make converging and diverging synaptic connections with distinct partner types. Whether synapses involving separate partners demonstrate similar or distinct structural motifs is not yet well understood. We thus used serial electron microscopy in mouse retina to map output synapses of cone bipolar cells (CBCs) and compare their structural arrangements across bipolar types and postsynaptic partners. Three presynaptic configurations emerge-single-ribbon, ribbonless, and multiribbon synapses. Each CBC type exploits these arrangements in a unique combination, a feature also found among rabbit ON CBCs. Though most synapses are dyads, monads and triads are also seen. Altogether, mouse CBCs exhibit at least six motifs, and each CBC type uses these in a stereotypic pattern. Moreover, synapses between CBCs and particular partner types appear biased toward certain motifs. Our observations reveal synaptic strategies that diversify the output within and across CBC types, potentially shaping the distinct functions of retinal microcircuits., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Abstract: Only a few meta-analyses evaluated the effect of finerenone on cardiovascular events in type 2 diabetes mellitus with chronic kidney disease. The main aim of this meta-analysis was to gain more reliable assessments of the efficacy and safety of finerenone for prevention of cardiovascular events in diabetic kidney disease. We searched for finerenone in the treatment of diabetic kidney disease from database (PubMed, Embase, and ClinicalTrials.gov ) until December 30, 2021. Relative risks (RRs) with 95% confidence intervals (CIs) calculated by the Mantel-Haenszel random-effects model were used as summary statistics for the categorical data. We included 4 studies that met the inclusion criteria with 13,943 participants. The finerenone group demonstrated a great benefit in reducing the incidence of major adverse cardiac events (RR: 0.88; 95% CI 0.80-0.96; P = 0.003), all-cause mortality (RR: 0.89; 95% CI 0.80-0.99; P = 0.04), myocardial infarction (RR: 0.79; 95% CI 0.67-0.92; P = 0.003), and new-onset hypertension (RR: 0.71; 95% CI 0.62-0.81; P < 0.00001). No difference was found in adverse events between the finerenone and placebo groups (RR: 1.00; 95% CI [0.98-1.01], P = 0.59), whereas a higher risk of hyperkalemia was observed in the finerenone group than in the placebo group (RR = 2.04, 95% CI 1.80-2.32; P < 0.00001). Besides, cerebrovascular events and new-onset atrial fibrillation did not increase in patients taking finerenone. Overall, finerenone treatment showed a great benefit of reducing the risk of major adverse cardiac events, all-cause mortality, myocardial infarction, and new-onset hypertension events in patients with type 2 diabetes mellitus and chronic kidney disease., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

A new protocol is herein described for the direct generation of alkylated indolo/benzoimidazo[2,1- a ]isoquinolin-6(5 H )-one derivatives by using Hantzsch esters as alkylation radical precursors using a photoredox/K 2 S 2 O 8 system. This oxidative alkylation of active alkenes involves a radical cascade cyclization process and a sequence of Hantzsch ester single electron oxidation, C-C bond cleavage, alkylation, arylation and oxidative deprotonation.

This study aimed to determine the values of the half-effective dose (ED 50 ) and 95% effective dose (ED 95 ) of remimazolam besylate used in the procedural sedation of endoscopic retrograde cholangiopancreatography (ERCP). Sixty patients who fulfilled the inclusion and exclusion criteria of this study were selected. Sufentanil was administered intravenously and remimazolam besylate was administered 2 min later. ERCP treatment was feasible when the modified alertness/sedation (MOAA/S) score was ≤2. If choking or movement occurred during duodenoscope placement, it was considered as a positive reaction. The dose was increased in the next patient; otherwise, it was considered as a negative reaction, and the dose was reduced in the next patient. The ED 50 and ED 95 values and 95% confidence interval (CI) of remimazolam besylate were calculated by Probit regression analysis. All 60 patients completed the trial. The ED 50 and ED 95 values of remimazolam besylate were 0.196 and 0.239 mg/kg, respectively, for the procedural sedation of ERCP. The time of MOAA/S score ≤ 2 was (82.58 ± 21.70) s, and the mean time of awakening was (9.03 ± 5.64) min. Transient hypotension was observed in two patients without medical intervention. The ED 50 and ED 95 values of remimazolam besylate used in the procedural sedation of ERCP were 0.196 and 0.239 mg/kg, and the dose of the medications has definite efficacy and good safety., Competing Interests: Jin Tian is a member of Ibrain's editorial board, but is not involved in the peer‐review process of this article. The remaining authors declare no conflict of interest., (© 2022 The Authors. Ibrain published by Affiliated Hospital of Zunyi Medical University and Wiley‐VCH GmbH.)

Obesity is characterized by lipid accumulation in distinct organs. Presently, fenofibrate is a commonly used triglyceride-lowering drug. This study is designed to investigate whether long-term fenofibrate intervention can attenuate lipid accumulation in ob/ob mouse, a typical model of obesity. Our data demonstrated that fenofibrate intervention significantly decreased plasma triglyceride level by 21.0%, increased liver index and hepatic triglyceride content by 31.7 and 52.1%, respectively, and elevated adipose index by 44.6% compared to the vehicle group. As a PPARα agonist, fenofibrate intervention significantly increased the expression of PPARα protein in the liver by 46.3% and enhanced the expression of LDLR protein by 3.7-fold. However, fenofibrate dramatically increased the expression of PPARγ and SREBP-1c proteins by ~2.1- and 0.9-fold in the liver, respectively. Fenofibrate showed no effects on the expression of genes-related to fatty acid β-oxidation. Of note, it significantly increased the gene expression of FAS and SCD-1 . Furthermore, fenofibrate modulated the gut microbiota. Collectively, long-term fenofibrate induces lipid accumulation in liver and adipose tissues in ob/ob mice by enhancing the expression of adipogenesis-related proteins and gut microbiota. These data suggest that fenofibrate may have limited effects on attenuating lipid deposition in obese patients., 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 Zhang, Jia, Liu, Yu, Si and Guo.)

Objective: To investigate the regulatory relationship of Protein Phosphatase 2 Regulatory Subunit B"Alpha ( PPP2R3A ) and hexokinase 1 ( HK1 ) in glycolysis of hepatocellular carcinoma (HCC)., Methods: In HepG2 and Huh7 cells, PPP2R3A expression was silenced by small interfering RNA (siRNA) and overexpression by plasmid transfection. The PPP2R3A -related genes were searched by RNA sequencing. Glycolysis levels were measured by glucose uptake and lactate production. QRT-PCR, ELISA, western blot and immunofluorescence assay were performed to detect the changes of PPP2R3A and HK1 . Cell proliferation, migration and invasion assay were used to study the roles of HK1 regulation by PPP2R3A ., Results: RNA sequencing data revealed that PPP2R3A siRNA significantly downregulated the expression of HK1 . PPP2R3A gene overexpression promotes, while gene silencing suppresses, the level of HK1 and glycolysis in HCC cells. In HCC tissue samples, PPP2R3A and HK1 were colocalized in the cytoplasm, and their expression showed a positive correlation. HK1 inhibition abrogated the promotion of glycolysis, proliferation, migration and invasion by PPP2R3A overexpression in liver cancer cells., Conclusion: Our findings showed the correlation of PPP2R3A and HK1 in the glycolysis of HCC, which reveals a new mechanism for the oncogenic roles of PPP2R3A in cancer., (Copyright © 2022 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Cordyceps militaris is a parasitic edible fungus and has been used as tonics for centuries. Polysaccharides are a major water-soluble component of C. militaris . Recently, C. militaris -derived polysaccharides have been given much attention due to their various actions including antioxidant, anti-inflammatory, anti-tumor, anti-hyperlipidemic, anti-diabetic, anti-atherosclerotic, and immunomodulatory effects. These bioactivities are determined by the various structural characteristics of polysaccharides including monosaccharide composition, molecular weight, and glycosidic linkage. The widespread use of advanced analytical analysis tools has greatly improved the elucidation of the structural characteristics of C. militaris -derived polysaccharides. However, the methods for polysaccharide structural characterization and the latest findings related to C. militaris -derived polysaccharides, especially the potential structure-activity relationship, have not been well-summarized in recent reviews of the literature. This review will discuss the methods used in the elucidation of the structure of polysaccharides and structural characteristics as well as the signaling pathways modulated by C. militaris -derived polysaccharides. This article provides information useful for the development of C. militaris -derived polysaccharides as well as for investigating other medicinal polysaccharides., 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 Miao, Yu, Li, Sun and Guo.)

The number of smoking patients receiving anesthesia and surgical treatment is increasing day by day. It will be useful for medical advancement to explore whether smoking is an independent risk factor for postoperative cognitive impairment. A double-blind, parallel, and controlled study was conducted on 112 patients who fulfilled the criteria for inclusion in this study and planned to undergo painless gastroscopy under general anesthesia. The baseline mini-mental state examination (MMSE) scores and basic information were collected. The changes in the MMSE scores after waking up and 3 days after anesthesia were observed, and the adverse events (respiratory adverse reactions, circulatory fluctuations, and adverse reactions, drug use, etc.) were analyzed by logistic regression. The baseline level of each group is consistent, which is worth studying. The MMSE score of the smoking group after anesthesia was significantly different from that of the control group ( p  < 0.05), but there was no significant difference between the two groups 3 days after anesthesia. Among them, the differences in adverse events between the two groups were in terms of hiccup, postoperative cough, and SpO 2  < 90% ( p  < 0.05). Regression analysis indicates that smoking after anesthesia leads to the occurrence of postoperative cough. Smoking is probably an independent risk factor for post-operative cognitive dysfunction (POCD) in early postoperative patients., Competing Interests: Zhao‐Qiong Zhu and Yu‐Hang Zhu are reviewers for Ibrain but are not involved in the peer review process of this manuscript. Other authors declare no conflict of interest., (© 2022 The Authors. Ibrain published by Affiliated Hospital of Zunyi Medical University and Wiley‐VCH GmbH.)

A method for the preparation of 3-alkylated spiro[4.5]trienones via alkylation/ipso-cyclization of activated alkynes with 4-alkyl-DHPs under transition-metal-free conditions is proposed. This alkylation successively undergoes the generation of alkyl radicals, addition of alkyl radicals to the alkynes, and intramolecular ipso-cyclization. The mechanism studies suggest that the alkylation/ipso-cyclization involves a radical process. This ipso-cyclization procedure shows a series of advantages, such as accessibility, mild conditions, high efficiency, greater safety, and an environmentally friendly method.

An N -glycosidic polysaccharide-peptide complex CMPS-80 was obtained from the fruiting body of C. militaris . Of importance, CMPS-80 significantly ameliorated formation of atherosclerotic lesions and plasma lipid profiles in apolipoprotein E-deficient mice. Integrated informatics analysis suggested that CMPS-80 can modulate multiple lncRNA-microRNA-mRNA axes. CMPS-80 has a potential application for prevention of hyperlipidemia and atherosclerosis.

The transition-metal-free alkylation/cyclization of activated alkenes using Hantzsch ester derivatives as effective alkyl reagents is described. A wide variety of valuable oxindoles was constructed in a single step with excellent selectivity. The reaction occurs through the formation of alkyl radical species followed by the tandem addition/annulation of olefins under oxidative conditions. This protocol is expected to offer inspiration for developing novel and efficient applications of Hantzsch esters in organic synthesis.

Purpose: To investigate the relationship between size of different connectors and bending strength of cast porcelain materials., Methods: The samples were divided into 5 groups according to the area of all-porcelain materials and simulated connector. In group A, simulated connector with cast porcelain material with a cross-section of 2 mm×3 mm was selected; In group B, simulated connector with cast porcelain material with a cross-section of 2 mm×4 mm was selected; In group C, simulated connector with cast porcelain material with a cross-section of 3 mm×3 mm was selected; In group D, simulated connector with cast porcelain material with a cross-section of 3 mm×4 mm was selected; In group E, simulated connector with zirconium oxide material with a cross-section of 2 mm×3 mm was selected. The fracture load was tested using classical three-point bending experiment, statistical analysis was performed using SPSS 18.0 software package., Results: For lithium disilicate cast porcelain, the fracture load increased with increasing cross section area, but both below the shear zirconia fracture load with a cross section of 2 mm×3 mm(P＜0.05).The increase in width increased the fracture load of porcelain samples compared to the length., Conclusions: It is suitable to increase linker area when cast porcelain is applied to single-end bridge, which is especially achieved by increasing the width at the linker.

Ethnopharmacological Relevance: With the features of multiple-components and targets as well as multifunction, traditional Chinese medicine (TCM) has been widely used in the prevention and treatment of various diseases for a long time. During the application of TCM, the researches about bioavailability enhancement of the bioactive constituents in formula are flourishing. Bushen-Yizhi formula (BSYZ), a TCM prescription with osthole (OST) as one of the main bioactive ingredients, have been widely used to treat kidney deficiency, mental retardation and Alzheimer's disease. However, the underlying biological mechanism and compound-enzyme interaction mediated bioavailability enhancement of OST are still not clearly illuminated., Aim of the Study: The aim of this study is to explore the material basis and molecular mechanism from BSYZ in the bioavailability enhancement of OST. Screening the potential CYP3A4 inhibitors using theoretical prediction and then verifying them in vitro, and pharmacokinetics study of OST in rat plasma under co-administrated of screened CYP3A4 inhibitors and BSYZ were also scarcely reported., Materials and Methods: Screening of CYP3A4 inhibitors from BSYZ was performed with molecular docking simulation from systems pharmacology database. The screened compounds were verified by using P450-Glo Screening Systems. A multiple reaction monitoring (MRM) mass spectrometry method was established for OST quantification. Male Sprague-Dawley rats divided into four groups and six rats in each group were employed in the pharmacokinetics study of OST. The administrated conditions were group I, OST (20 mg/kg); group II, BSYZ (containing OST 1 mg/mL, at the dose of 20 mg/kg OST in BSYZ); group III, co-administration of ketoconazole (Ket, 75 mg/kg) and OST (20 mg/kg); group IV, co-administration of CYP3A4 inhibitor (10 mg/kg) and OST (20 mg/kg). They were determined by using HPLC-MS/MS (MRM) and statistical analysis was performed using student's t-test with p < 0.05 as the level of significance., Results: 21 potential CYP3A4 inhibitors were screened from BSYZ compounds library. From the results of verification in vitro, we found 4 compounds with better CYP3A4 inhibition efficiency including Oleic acid, 1,2,3,4,6-O-Pentagalloylglucose, Rutin, and Schisantherin B. Under further verification, Schisantherin B exhibited the best inhibitory effect on CYP3A4 (IC 50  = 0.339 μM), and even better than the clinically used drug (Ket) at the concentration of 5 μM. In the study of pharmacokinetics, the area under the curve (AUC, ng/L*h) of OST after oral administration of BSYZ, Ket and Schisantherin B (2196.23 ± 581.33, 462.90 ± 92.30 and 1053.03 ± 263.62, respectively) were significantly higher than that of pure OST treatment (227.89 ± 107.90, p < 0.01)., Conclusions: Schisantherin B, a profoundly effective CYP3A4 inhibitor screened from BSYZ antagonized the metabolism of CYP3A4 on OST via activity inhibition, therefore significantly enhanced the bioavailability of OST in rat plasma. The results of this study will be helpful to explain the rationality of the compatibility in TCM formula, and also to develop new TCM formula with more reasonable drug compatibility., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Myocardial ischemia/reperfusion (I/R) injury is still a lack of effective therapeutic drugs, and its molecular mechanism is urgently needed. Studies have shown that the intestinal flora plays an important regulatory role in cardiovascular injury, but the specific mechanism has not been fully elucidated. In this study, we found that an increase in Ang II in plasma was accompanied by an increase in the levels of myocardial injury during myocardial reperfusion in patients with cardiopulmonary bypass. Furthermore, Ang II treatment enhanced mice myocardial I/R injury, which was reversed by caveolin-1 (CAV-1)-shRNA or strengthened by angiotensin-converting enzyme 2 (ACE2)-shRNA. The results showed that CAV-1 and ACE2 have protein interactions and inhibit each other's expression. In addition, propionate, a bacterial metabolite, inhibited the elevation of Ang II and myocardial injury, while GPR41-shRNA abolished the protective effects of propionate on myocardial I/R injury. Clinically, the propionate content in the patient's preoperative stool was related to Ang II levels and myocardial I/R injury levels during myocardial reperfusion. Taken together, propionate alleviates myocardial I/R injury aggravated by Ang II dependent on CAV-1/ACE2 axis through GPR41, which provides a new direction that diet to regulate the intestinal flora for treatment of myocardial I/R injury., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Cordyceps militaris is cultured widely as an edible mushroom and accumulating evidence in mice have demonstrated that the polysaccharides of Cordyceps species have lipid-lowering effects. However, lipid metabolism in mice is significantly different from that in humans, making a full understanding of the mechanisms at play critical., Methods: After 5 months, the hamsters were weighed and sampled under anesthesia after overnight fasting. The lipid-lowering effect and mechanisms of the polysaccharide CM1 was investigated by cellular and molecular technologies. Furthermore, the effect of the polysaccharide CM1 (100 μg/mL) on inhibiting adipocyte differentiation was investigated in vitro., Results: CM1, a polysaccharide from C. militaris, significantly decreased plasma total cholesterol, triglyceride and epididymal fat index in LDLR (+/-) hamsters, which have a human-like lipid profile. After 5 months' administration, CM1 decreased the plasma level of apolipoprotein B48, modulated the expression of key genes and proteins in liver, small intestine, and epididymal fat. CM1 also inhibited preadipocyte differentiation in 3T3-L1 cells by downregulating the key genes involved in lipid droplet formation., Conclusions: The polysaccharide CM1 lowers lipid and adipocyte differentiation by several pathways, and it has potential applications for hyperlipidemia prevention., (© 2021. The Author(s).)

Atherosclerotic cardiovascular disease has a high mortality worldwide. Our lab previously purified a polysaccharide designated as CM1 with (1→4)-β-D-Glc p and (1→2)-α-D-Man p glycosyls as the backbone. In this study, we investigated the anti-atherosclerosis effect of CM1 and the underlying mechanisms of action in a low-density lipoprotein receptor knockout (LDLR (-/-) mouse model. It was found that CM1 significantly decreased the formation of atherosclerotic plaques. Mechanistically, CM1 enhanced plasma level of apolipoprotein A-I and decreased the plasma levels of triglyceride, apolipoprotein B, and total cholesterol. In the absence of LDLR, CM1 elevated the expression of very low-density lipoprotein receptor for liver uptake of plasma apolipoprotein B-containing particles and reduced hepatic triglyceride synthesis by inhibiting sterol regulatory element binding protein 1c. CM1 improved lipids excretion by increasing the liver X receptor α/ATP-binding cassette G5 pathway in small intestine. CM1 reduced lipogenesis and lipolysis by inhibiting peroxisome proliferator-activated receptor γ and adipose triglyceride lipase in epididymal fat. Furthermore, CM1 improved lipid profile in C57BL/6J mice. Collectively, CM1 can modulate lipid metabolism by multiple pathways, contributing to reduced plasma lipid level and formation of atherosclerotic plaques in LDLR (-/-) mice. This molecule could be explored as a potential compound for prevention and treatment of hyperlipidemia and atherosclerosis., 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 Yin, Lin, Yu, Shen, Li and Guo.)

Enterogenous infection is a major cause of death during traumatic hemorrhagic shock (THS). It has been reported that Toll-like receptor 5 (TLR5) plays an integral role in regulating mucosal immunity and intestinal homeostasis of the microbiota. However, the roles played by TLR5 on intestinal barrier maintenance and commensal bacterial translocation post-THS are poorly understood. In this research, we established THS models in wild-type (WT) and Tlr5 -/- (genetically deficient in TLR5 expression) mice. We found that THS promoted bacterial translocation, while TLR5 deficiency played a protective role in preventing commensal bacteria dissemination after THS. Furthermore, intestinal microbiota analysis uncovered that TLR5 deficiency enhanced the mucosal biological barrier by decreasing RegIII γ -mediated bactericidal activity against G + anaerobic bacteria. We then sorted small intestinal TLR5 + lamina propria dendritic cells (LPDCs) and analyzed T H 1 differentiation in the intestinal lamina propria and a coculture system consisting of LPDCs and naïve T cells. Although TLR5 deficiency attenuated the regulation of T H 1 polarization by LPDCs, it conferred stability to the cells during THS. Moreover, retinoic acid (RA) released from TLR5 + LPDCs could play a key role in modulating T H 1 polarization. We also found that gavage administration of RA alleviated bacterial translocation in THS-treated WT mice. In summary, we documented that TLR5 signaling plays a pivotal role in regulating RegIII γ -induced killing of G + anaerobic bacteria, and LPDCs mediated T H 1 differentiation via RA. These processes prevent intestinal bacterial translocation and enterogenous infection after THS, suggesting that therapeutically targeting LPDCs or gut microbiota can interfere with bacterial translocation after THS., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 Yun Zhang et al.)

Protein elicitors can induce plant systemic resistance to pathogens. In an earlier study, we cloned an EsxA gene from the plant growth-promoting rhizobacterium Paenibacillus terrae NK3-4 and expressed it in Pichia pastoris. In addition to being important for the pathogenicity of animal pathogens, EsxA can also induce an immune response in animals. While, we found the exogenously expressed EsxA has the activity of elicitor, which can trigger hypersensitive response and reactive oxygen species burst in leaves as well as enhanced rice plant growth. The effects of EsxA on seedling blight (Fusarium oxysporum) resistance and gene transcription, including pathogenesis-related (PR) genes in rice were evaluated. The germination rate was 95.0% for seeds treated with EsxA and then inoculated with F. oxysporum, which was 2.8-times higher than that of F. oxysporum-infected control seeds that were not treated with EsxA (Con). The buds and roots of EsxA-treated seedlings were 2.4- and 15.9-times longer than those of Con seedlings. The plants and roots of seedlings dipped in an EsxA solution and then inoculated with F. oxysporum were longer than those of the Con seedlings. Theplant length, number of total roots, and number of white roots were respectively 23.2%, 1.74-times, and 7.42-times greater for the seedlings sprayed with EsxA and then inoculated with F. oxysporum than for the Con seedlings. The EsxA induction efficiency (spray treatment) on seedling blight resistance was 60.9%. The transcriptome analysis revealed 1137 and 239 rice genes with EsxA-induced up-regulated and down-regulated transcription levels, respectively. At 48 h after the EsxA treatment, the transcription of 611 and 160 genes was up-regulated and down-regulated, respectively, compared with the transcription levels for the untreated control at the same time-point. Many disease resistance-related PR genes had up-regulated transcription levels. The qPCR data were consistent with the transcriptome sequencing results. EsxA triggered rice ISR to seedling blight and gene differential transcription, including the up-regulated transcription of rice PR genes. These findings may be relevant for the use of EsxA as a protein elicitor to control plant diseases., (© 2021. The Author(s).)

A convenient and efficient visible-light-induced tandem acylation/cyclization of N -propargylindoles with aryl- or alkyl-substituted acyl oxime esters for the synthesis of 2-acyl-substituted 9 H -pyrrolo[1,2- a ]indoles under transition-metal-free conditions, which proceeds via nitrogen-centered radical-mediated cleavage of the C-C σ-bond in acyl oxime esters, is established. The aryl or alkyl acyl radicals, which come from acyl oxime esters, attack the C-C triple bonds in N -propargylindoles and then go through intramolecular cyclization/isomerization.

Background: The Revised Atlanta Classification (RAC) and Determinant-Based Classification (DBC) are currently two widely adopted systems for evaluating the severity of acute pancreatitis (AP). This study aimed to overcome the inaccuracies and limitations that existed in them., Methods: We retrospectively analyzed 298 patients with AP. The "Two-Step" approach was divided into an early organ failure (OF) assessment: (I) none, (II) transient, (III) single persistent, and (IV) multiple persistent; and a later local complications assessment: (A) none, (B) sterile, and (C) infectious. Patients with AP who died before the second step were classified into category X. The "Two-Step" approach was then compared to the RAC and DBC., Results: As the patients' grades increased (I to IV), organ support treatment rates, intensive care unit lengths of stay, and mortalities increased. Invasive intervention rates displayed increasing trends with local complications aggravated (A to C). Patients in category X were older and had higher Marshall scores with the highest grades of severity., Conclusions: By combining the early OF grades and the late local complications, the "Two-Step" approach represents an accurate classification system required for stratified studies of AP, and introduces the category X as the severest forms of AP., (© 2021 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Renin-angiotensin-aldosterone system activation is the critical factor in renal remodeling and dysfunction. Our previous study suggested that miR-29b may attenuate AngII-induced renal intestinal fibrosis in vitro. In the present study, we aimed to determine whether recombinant rAAV9-mediated miR-29b delivery protects against AngII-induced renal fibrosis and dysfunction., Method: Mice were treated with AngII via osmotic mini-pumps, or phosphate-buffered saline. rAAV9 vectors were produced using the rBac-based system in SF9 cells. rAAV9-miR-29b or rAAV9-control-miR was injected into the kidneys of mice subjected to the model of AngII infusion. The role of miR-29b in renal fibrosis was assessed using quantitative polymerase chain reaction, western blot, and histology., Results: In AngII-induced fibrotic kidney tissue, miR-29b expression was downregulated. rAAV9-miR-29b delivery significantly reversed renal injury as indicated by decreased serum creatinine and injury related gene expression in AngII-infused mice. Regarding organ remodeling, tubulointerstitial fibrosis and deposition of extracellular matrix components such as collagen type I and type III were significantly decreased in renal tissue from mice delivered rAAV9-miR-29b., Conclusion: Our results demonstrate great potential for use of rAAV9 as an applicable vector for delivery of miR-29b as an antifibrogenic factor for treatment of tubulointerstitial fibrosis-induced renal injury., (© 2021. The Author(s).)

Plasma free fatty acids (FFAs) are elevated in obesity and can induce insulin resistance via endoplasmic reticulum (ER) stress. However, it is unknown whether hepatic insulin resistance caused by the elevation of plasma FFAs is alleviated by chemical chaperones. Rats received one of the following i.v. treatments for 48 h: saline, intralipid plus heparin (IH), IH plus the chemical chaperone 4-phenylbutyric acid (PBA), or PBA alone and a hyperinsulinemic-euglycemic clamp was performed during the last 2 h. PBA co-infusion normalized IH-induced peripheral insulin resistance, similar to our previous findings with an antioxidant and an IκBα kinase β (IKKβ) inhibitor. Different from our previous results with the antioxidant and IKKβ inhibitor, PBA also improved IH-induced hepatic insulin resistance in parallel with activation of Akt. Unexpectedly, IH did not induce markers of ER stress in the liver, but PBA prevented IH-induced elevation of phosphorylated eukaryotic initiation factor-2α protein in adipose tissue. PBA tended to decrease circulating fetuin-A and significantly increased circulating fibroblast growth factor 21 (FGF21) without affecting markers of activation of hepatic protein kinase C-δ or p38 mitogen-activated protein kinase that we have previously involved in hepatic insulin resistance in this model. In conclusion: (i) PBA prevented hepatic insulin resistance caused by prolonged plasma FFA elevation without affecting hepatic ER stress markers; (ii) the PBA effect is likely due to increased FGF21 and/or decreased fetuin-A, which directly signal to upregulate Akt activation.

Regulatory T cells (Tregs) expressing the Foxp3 transcription factor are indispensable for the maintenance of immune system homeostasis. Tregs may lose Foxp3 expression or be reprogrammed into cells that produce proinflammatory cytokines, for example, Th1-like Tregs, Th2-like Tregs, Th17-like Tregs, and Tfh-like Tregs. Accordingly, selective therapeutic molecules that manipulate Treg lineage stability and/or functional activity might have the potential to improve aberrant immune responses in human disorders. In particular, the transcription factor Helios has emerged as an important marker and modulator of Tregs. Therefore, the current review focuses on recent findings on the expression, function, and mechanisms of Helios, as well as the patterns of Foxp3 + Tregs coexpressing Helios in various human disorders, in order to explore the potential of Helios for the improvement of many immune-related diseases. The studies were selected from PubMed using the library of the Nanjing Medical University in this review. The findings of the included studies indicate that Helios expression stabilizes the phenotype and function of Foxp3 + Tregs in certain inflammatory environments. Further, Tregs coexpressing Helios and Foxp3 were identified as a specific phenotype of stronger suppressor immune cells in both humans and animal models. Importantly, there is ample evidence that Helios-expressing Foxp3 + Tregs are relevant to various human disorders, including connective tissue diseases, infectious diseases, solid organ transplantation-related immunity, and cancer. Thus, Helios + Foxp3 + CD4 + Tregs could be a valuable target in human diseases, and their potential should be explored further in the clinical setting., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Wen-qing Yu et al.)

Purpose: This study aimed at exploring the effect of berberine (C20H18NO4) on osteogenic differentiation of rat adipose-derived stem cells(ADSCs) and clarifying the related mechanism., Methods: ADSCs were subjected to 5, 10, 20 μmol/L berberine culture solution. The untreated ADSCs were set as the control group. Cell proliferation activity was determined by MTT method. Alkaline phosphatase (ALP) staining, semi-quantitative assay and alizarin red staining (ARS) were applied to analyze the effect of berberine on osteogenic differentiation of ADSCs. The phosphorylation level of c-Jun amino terminal kinase (JNK) protein was tested by Western blot. Runx2, OCN were tested by Western blot before and after application of JNK pathway inhibitor SP600125. SPSS 22.0 software package was used for statistical analysis., Results: There was no significant difference on cell proliferation activity of ADSCs treated with 5, 10 and 20 μmol/L berberine at 1, 3 and 7 day(P>0.05). ALP staining and ARS staining in groups treated by berberine were significantly darker than those of the control group, and ALP protein secretion in the experimental group was significantly up-regulated (P<0.05). The phosphorylation level of JNK was increased after treated with 10 μmol/L berberine culture medium. The expression of osteogenic related proteins Runx2 and OCN was up-regulated in the experimental group. After inhibition of JNK signaling pathway, the expression of Runx2 and OCN was down-regulated., Conclusions: Berberine has no effect on cell proliferation of ADSCs, and can up-regulate osteogenic differentiation of ADSCs through activation of JNK signaling pathway.

Background: This study aimed to identify variables associated with anastomotic leakage after esophagectomy and established a tool for anastomotic leakage prediction., Methods: Twenty-six preoperative and postoperative variables were retrospectively collected from esophageal cancer patients who were treated with radical esophagectomy from January 2018 to June 2020 in the Affiliated Hospital of Qingdao University. SPSS Version 23.0 and Empower Stats software were used for establishing a nomogram after screening relevant variables by univariate and multivariate Logistic regression analyses. The established nomogram was identified by depicting the receiver operating characteristic (ROC) curves and calibration curve, which was verified by 1,000 bootstrap resamples method., Results: A total of 604 eligible esophageal cancer patients were included, of which 51 (8.4%) patients had anastomotic leakage. Multivariate Logistic regression analysis showed that smoking, anastomotic location, anastomotic technique, prognostic nutritional index (PNI) and ASA score were independent risks of anastomotic leakage. The area under curve (AUC) of ROC in the established nomogram was 0.764 (95% CI, 0.69-0.83). The internal validation confirmed that the nomogram had a great discrimination ability (AUC =0.766). Depicted calibration curve demonstrated a well-fitted prediction and observation probability. In addition, the decision curve analysis concluded that the newly established nomogram is significant for clinical decision-making., Conclusions: This nomogram provided the individual prediction of anastomotic leakage for esophageal cancer patients after surgery, which might benefit treatment results for patients and clinicians, as well as pre-and postoperative intervention strategy-making., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-21-209). The authors have no conflicts of interest to declare., (2021 Journal of Thoracic Disease. All rights reserved.)

An EsxA-encoding gene (esxA) was previously identified in the genome of the plant growth-promoting rhizobacterium Paenibacillus terrae strain NK3-4. The esxA was cloned and expressed in Pichia pastoris, after which the effects of the EsxA protein on rice seedling growth were analyzed to determine whether EsxA contributes to the plant growth-promoting activity of strain NK3-4. The esxA was successfully cloned from the NK3-4 genome and ligated to the eukaryotic expression vector pPICZαA. The resulting pPICZαA-esxA recombinant plasmid was transinfected into yeast cells, and esxA expression in the yeast cells was confirmed. The treatment of seed- buds with the EsxA protein increased the root length by 1.35-times, but decreased the bud length. Additionally, in rice seedlings treated with EsxA, the root and shoot lengths increased by 2.6- and 1.7-times, respectively. These findings imply that EsxA is important for the promotion of rice plant growth by P. terrae strain NK3-4. Furthermore, the construction of the esxA expression vector and the engineered strain may be useful for future investigations of the mechanism underlying the plant growth-promoting effects of EsxA, with implications for the application of EsxA for regulating plant growth.

In the retina, amacrine interneurons inhibit retinal ganglion cell (RGC) dendrites to shape retinal output. Amacrine cells typically use either GABA or glycine to exert synaptic inhibition. Here, we combined transgenic tools with immunohistochemistry, electrophysiology, and 3D electron microscopy to determine the composition and organization of inhibitory synapses across the dendritic arbor of a well-characterized RGC type in the mouse retina: the ON-sustained alpha RGC. We find mixed GABA-glycine receptor synapses across this RGC type, unveiling the existence of "mixed" inhibitory synapses in the retinal circuit. Presynaptic amacrine boutons with dual release sites are apposed to ON-sustained alpha RGC postsynapses. We further reveal the sequence of postsynaptic assembly for these mixed synapses: GABA receptors precede glycine receptors, and a lack of early GABA receptor expression impedes the recruitment of glycine receptors. Together our findings uncover the organization and developmental profile of an additional motif of inhibition in the mammalian retina., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Delayed treatment of seriously infected patients results in increased mortality. However, antimicrobial therapy for the initial 24 to 48 hours is mostly empirically provided, without evidence regarding the causative pathogen. Whether empiric anti-enterococcal therapy should be administered to treat intra-abdominal infection (IAI) before obtaining culture results remains unknown. We performed a meta-analysis to explore the effects of empiric enterococci covered antibiotic therapy in IAI and the risk factors for enterococcal infection in IAI. Methods: We searched multiple databases systematically and included 23 randomized controlled trials (RCTs) and 13 observational studies. The quality of included studies was assessed, and the reporting bias was evaluated. Meta-analysis was performed using random effects or fixed effects models according to the heterogeneity. The risk ratio (RR), odds ratio (OR), and 95% confidence interval (CI) were calculated. Results: Enterococci-covered antibiotic regimens provided no improvement in treatment success compared with control regimens (RR, 0.99; 95% CI, 0.97-1.00; p = 0.15), with similar mortality and adverse effects in both arms. Basic characteristic analysis revealed that most of the enrolled patients with IAI in RCTs were young, lower risk community-acquired intra-abdominal infection (CA-IAI) patients with a relatively low APACHE II score. Interestingly, risk factor screening revealed that malignancy, corticosteroid use, operation, any antibiotic treatment, admission to intensive care unit (ICU), and indwelling urinary catheter could predispose the patients with IAI to a substantially higher risk of enterococcal infection. "Hospital acquired" itself was a risk factor (OR, 2.81; 95% CI, 2.34-3.39; p < 0.001). Conclusion: It is unnecessary to use additional agents empirically to specifically provide anti-enterococcal coverage for the management of CA-IAI in lower risk patients without evidence of causative pathogen, and risk factors can increase the risk of enterococcal infection. Thus, there is a rationale for providing empiric anti-enterococcal coverage for severely ill patients with CA-IAI with high risk factors and patients with hospital-acquired intra-abdominal infection (HA-IAI).

Objective: To evaluate the biomechanical behaviors of different framework materials in implant-supported fixed mandibular prosthesis using three-dimensional finite element analysis. Methods: A model of implant-supported fixed mandibular prosthesis was established. The simulations were divided into six groups according to the framework materials: pure titanium, cobalt-chromium alloy, gold alloy, zirconia, polyether ether ketone (PEEK) and carbon fiber-reinforced PEEK. An oblique load of 300 N with a 75° angle to the occlusal plane was applied from the lingual side on the buccal cusps of the two premolars and the first molar teeth. The stresses on implants, surrounding bones and frameworks were analyzed and compared among the framework materials both quantitatively and qualitatively. Results: In implant-supported fixed mandibular prosthesis model, the highest stresses were located around the neck of the implants and cortical bone during oblique loading among six designs. In addition, the stresses were concentrated on the buccal and distal cortical bone around the implants of the posterior region. Stress values of implants and cortical bones from low to high were as follows: zirconia, cobalt-chromium alloy, pure titanium, gold alloy, carbon fiber-reinforced PEEK, PEEK. The von Mises stress values of implant and cortical bone in the first molar site of PEEK framework material were 44.96 and 29.13 MPa, while the von Mises stress values of implant and cortical bone in the first molar site of zirconia framework material were 21.29 and 17.79 MPa. The zirconia and medal framework materials were more advantageous in stress distribution around implants than PEEK framework material. Conclusions: In implant-supported fixed mandibular prostheses, biomechanical analysis showed that the zirconia and medal framework materials were more advantageous in stress distribution around implants than PEEK framework materials.