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Developing an efficient drug delivery system to mitigate the harm caused by root-knot nematodes is crucial. In this study, enzyme-responsive release abamectin nanocapsules (AVB1a NCs) were prepared using 4, 4-diphenylmethane diisocyanate (MDI) and sodium carboxymethyl cellulose as response release factors. The results showed that the average size (D 50) of the AVB1a NCs was 352 nm, and the encapsulation efficiency was 92 %. The median lethal concentration (LC 50 ) of AVB1a NCs for Meloidogyne incognita activity was 0.82 mg L -1 . Moreover, AVB1a NCs improved the permeability of AVB1a to root-knot nematodes and plant roots and the horizontal and vertical soil mobility. Furthermore, AVB1a NCs greatly reduced the adsorption of AVB1a by the soil compared to AVB1a emulsifiable concentrate (EC), and the effect of the AVB1a NCs on controlling root-knot nematode disease was increased by 36 %. Compared to the AVB1a EC, the pesticide delivery system significantly reduced the acute toxicity to the soil biological earthworms by approximately 16 times that of the AVB1a and had a lower overall impact on the soil microbial communities. This enzyme-responsive pesticide delivery system had a simple preparation method, excellent performance, and high level of safety, and thus has great application potential for plant diseases and insect pests control., Competing Interests: Declaration of competing interest This manuscript has not been published or presented elsewhere in part or in entirety and is not under consideration by another journal. We have read and understood your journal's policies, and we believe that neither the manuscript nor the study violates any of these. There are no conflicts of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Sanjin tablets (SJT) are a well-known Chinese patent drug that have been used to treat urinary tract infections (UTIs) for the last 40 years. The drug consists of five herbs, but only 32 compounds have been identified, which hinders the clarification of its effective substances and mechanism. Methods: The chemical constituents of SJT and their effective substances and functional mechanism involved in the treatment of UTIs were investigated by using high performance liquid chromatography-electrospray ionization-ion trap-time of flight-mass spectrometry (HPLC-ESI-IT-TOF-MS n ), network pharmacology, and molecular docking. Results: A total of 196 compounds of SJT (SJT-MS) were identified, and 44 of them were unequivocally identified by comparison with the reference compounds. Among 196 compounds, 13 were potential new compounds and 183 were known compounds. Among the 183 known compounds, 169 were newly discovered constituents of SJT, and 93 compounds were not reported in the five constituent herbs. Through the network pharmacology method, 119 targets related to UTIs of 183 known compounds were predicted, and 20 core targets were screened out. Based on the "compound-target" relationship analysis, 94 compounds were found to act on the 20 core targets and were therefore regarded as potential effective compounds. According to the literature, 27 of the 183 known compounds were found to possess antimicrobial and anti-inflammatory activities and were verified as effective substances, of which 20 were first discovered in SJT. Twelve of the 27 effective substances overlapped with the 94 potential effective compounds and were determined as key effective substances of SJT. The molecular docking results showed that the 12 key effective substances and 10 selected targets of the core targets have good affinity for each other. Discussion: These results provide a solid foundation for understanding the effective substances and mechanism of SJT., Competing Interests: J-GM and XZ were employed by Guilin Sanjin Pharmaceutical Company Limited. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Li, Wang, Xu, Guo, Zhang, Lv, Wang, Wang, Min, Zou and Cai.)

Corneal organoids are cornea-like tissue structures that are developed from induced pluripotent stem cells or embryonic stem cells in vitro. They have similar anatomical characteristics and gene expression profiles to the human cornea. Although the culture of corneal organoids is difficult, expensive, and time-consuming, they can be tailored to reconstruct the physiological environment and the interaction between corneal cells in each layer, which suggests broad application prospects. In this article, we review the latest research progress and summarize the application of corneal organoids in the research of corneal development mechanisms, keratopathy pathogenesis, donor corneal transplantation, and corneal organoids-on-a-chip, in order to provide reference for further clinical corneal research concerning keratopathy models, drug screening, and personalized medicine.

Background: Pulmonary fibrosis is a major category of end-stage changes in lung diseases, characterized by lung epithelial cell damage, proliferation of fibroblasts, and accumulation of extracellular matrix. Peroxiredoxin 1 (PRDX1), a member of the peroxiredoxin protein family, participates in the regulation of the levels of reactive oxygen species in cells and various other physiological activities, as well as the occurrence and development of diseases by functioning as a chaperonin., Methods: Experimental methods including MTT assay, morphological observation of fibrosis, wound healing assay, fluorescence microscopy, flow cytometry, ELISA, western blot, transcriptome sequencing, and histopathological analysis were used in this study., Results: PRDX1 knockdown increased ROS levels in lung epithelial cells and promoted epithelial-mesenchymal transition (EMT) through the PI3K/Akt and JNK/Smad signalling pathways. PRDX1 knockout significantly increased TGF-β secretion, ROS production, and cell migration in primary lung fibroblasts. PRDX1 deficiency also increased cell proliferation, cell cycle circulation, and fibrosis progression through the PI3K/Akt and JNK/Smad signalling pathways. BLM treatment induced more severe pulmonary fibrosis in PRDX1-knockout mice, mainly through the PI3K/Akt and JNK/Smad signalling pathways., Conclusions: Our findings strongly suggest that PRDX1 is a key molecule in BLM-induced lung fibrosis progression and acts through modulating EMT and lung fibroblast proliferation; therefore, it may be a therapeutic target for the treatment of BLM-induced lung fibrosis., (© 2023. The Author(s).)

Two novel Gram-stain-negative, aerobic and rod-shaped bacterial strains, designated DHG64 T and 4D114 T , were isolated from forest soil of Dinghushan Biosphere Reserve, Guangdong Province, PR China. DHG64 T grew at 12-37 °C (optimum 33 °C), pH 4.5-10.0 (optimum 6.5-7.5) and in the presence of 0-2.0 % NaCl (w/v); while 4D114 T grew at 12-37 °C (optimum 20-33 °C), pH 4.0-7.0 (optimum 4.5-6.0) and in the presence of 0-1.0 % NaCl (w/v). DHG64 T and 4D114 T showed 97.1-98.0 and 97.5-98.4 % 16S rRNA gene sequence similarities with seven species of the genus Trinickia with validly published names, respectively. In the phylogenetic trees based on 16S rRNA gene and genome sequences, both strains formed a clade with the members of genus Trinickia but well separated from each other. The average nucleotide identity and digital DNA-DNA hybridisation values for the novel strains to all species of the genus Trinickia with validly published names were in the ranges of 80.6-85.0 and 22.4-28.0 %, respectively. DHG64 T contained C 16 : 0 , C 17 : 0 cyclo and C 19 : 0 cyclo ω8 c , while 4D114 T had C 16 : 0 , C 17 : 0 cyclo, C 19 : 0 cyclo ω8 c and summed feature 2 (iso-C 16 : 1 I and/or C 14 : 0 3-OH) as the major cellular fatty acids. The major polar lipids for strains DHG64 T and 4D114 T were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. The DNA G+C contents of DHG64 T and 4D114 T were 63.0 and 62.8 mol%, respectively. Genomic analyses indicated that DHG64 T and 4D114 T may have potential for various applications, such as developing drugs against certain health problems and restoring environments polluted with metal ions and/or benzoate. On the basis of the results of morphological, physiological, biochemical and phylogenetic analyses, strains DHG64 T and 4D114 T were classified as representing two novel species of the genus Trinickia , for which the names Trinickia mobilis sp. nov. (type strain DHG64 T = KACC 21223 T = GDMCC 1.1282 T ) and Trinickia acidisoli sp. nov. (type strain 4D114 T = KCTC 82876 T = GDMCC 1.2131 T ) are proposed.

Circular RNAs are covalently closed and non-coding in eukaryotes, which have tissue- specific and temporal-specific expression patterns whose biogenesis is regulated by transcription and splicing. Most circular RNAs are localized in the cytoplasm. The sequences and protein-binding elements of circular RNAs facilitate circular RNAs in exerting biological functions through complementary base pairing, regulating protein function or self-translation. Recent studies have revealed that N6-Methyladenosine (m6A), a prevalent post-transcriptional modification, can affect the translation, localization, and degradation of circular RNAs. Cutting-edge research into circular RNAs have benefitted from the development of high-throughput sequencing technology. Furthermore, the expansion of novel research methods has promoted progress into circular RNA research., (Copyright © 2023. Published by Elsevier Inc.)

Background: In randomized studies, the strategy of pulmonary vein antral isolation (PVI) plus linear ablation has failed to increase success rates for persistent atrial fibrillation (PeAF) ablation when compared with PVI alone. Peri-mitral reentry related atrial tachycardia due to incomplete linear block is an important cause of clinical failures of a first ablation procedure. Ethanol infusion (EI) into the vein of Marshall (EI-VOM) has been demonstrated to facilitate a durable mitral isthmus linear lesion., Objective: This trial is designed to compare arrhythmia-free survival between PVI and an ablation strategy termed upgraded '2C3L' for the ablation of PeAF., Study Design: The PROMPT-AF study (clinicaltrials.gov 04497376) is a prospective, multicenter, open-label, randomized trial using a 1:1 parallel-control approach. Patients (n = 498) undergoing their first catheter ablation of PeAF will be randomized to either the upgraded '2C3L' arm or PVI arm in a 1:1 fashion. The upgraded '2C3L' technique is a fixed ablation approach consisting of EI-VOM, bilateral circumferential PVI, and 3 linear ablation lesion sets across the mitral isthmus, left atrial roof, and cavotricuspid isthmus. The follow-up duration is 12 months. The primary end point is freedom from atrial arrhythmias of >30 seconds, without antiarrhythmic drugs, in 12 months after the index ablation procedure (excluding a blanking period of 3 months)., Conclusions: The PROMPT-AF study will evaluate the efficacy of the fixed '2C3L' approach in conjunction with EI-VOM, compared with PVI alone, in patients with PeAF undergoing de novo ablation., Competing Interests: Conflict of interest None reported., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Studies assessing the gut mucosal immune balance in HIV-infected patients using intestinal samples are scarce. In this study, we used intestinal mucosal specimens from the ileocecal region of seven immunological nonresponders (INRs), nine immunological responders (IRs), and six HIV-negative controls. We investigated T helper 17 (Th17) and T regulatory (Treg) cell counts and their ratio, zonula occludens-1 (ZO-1), intestinal fatty acid-binding protein (I-FABP), tumor necrosis factor-α, CD4 + T cell counts, HIV DNA, and cell-associated HIV RNA. The results showed that INRs had lower Th17 and higher Treg cell counts than IR, resulting in a significant difference in the Th17/Treg ratio between IRs and INRs. In addition, INRs had lower ZO-1 and higher I-FABP levels than IRs. The Th17/Treg ratio was positively associated with ZO-1 and negatively associated with I-FABP levels. There was a positive correlation between Th17/Treg ratio and CD4 + T cell counts and a negative correlation between the Th17/Treg ratio and HIV DNA in the intestine. Our study suggests that the imbalance of Th17/Treg in the intestine is a characteristic of incomplete immune reconstitution to antiretroviral therapy and is associated with intestinal damage.

Postoperative delirium (POD), which occurs in hospital up to 1-week post-procedure or until discharge, is a common complication, especially in older adult patients. However, the pathogenesis of POD remains unclear. Although damage to blood-brain barrier (BBB) integrity is involved in the neuropathogenesis of POD, the specific role of the BBB in POD requires further elucidation. Anaesthesia using 2% isoflurane for 4 h results in the upregulation of hippocampal receptor for advanced glycation end-products (RAGE) expression and β-amyloid accumulation in aged rats. The present study investigated the role of RAGE in BBB integrity and its mechanisms in POD-like behaviours. The buried food, open field and Y maze tests were used to evaluate neurobehavioural changes in aged mice following 2.5% sevoflurane anaesthesia administration with exploratory laparotomy. Levels of tight junction proteins were assessed by western blotting. Multiphoton in vivo microscopy was used to observe the ultrastructural changes in the BBB in the hippocampal CA1 region. Anaesthesia with surgery decreased the levels of tight junction proteins occludin and claudin 5, increased matrix metalloproteinases (MMPs) 2 and 9, damaged the ultrastructure of the BBB and induced POD-like behaviour. FPS-ZM1, a specific RAGE antagonist, ameliorated POD-like behaviour induced by anaesthesia and surgery in aged mice. Furthermore, FPS-ZM1 also restored decreased levels of occludin and claudin 5 as well as increased levels of MMP2 and MMP9. The present findings suggested that RAGE signalling was involved in BBB damage following anaesthesia with surgery. Thus, RAGE has potential as a novel therapeutic intervention for the prevention of POD., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2020 Deng et al.)

BACKGROUND Thyroid dysfunction has been proved to contribute to the occurrence of atrial fibrillation (AF), leading to the development of AF in animal models and clinical populations. This single-center study investigated the relationship between ultra-sensitive thyroid-stimulating hormone (uTSH) levels and the recurrence of atrial fibrillation (AF) in 575 hospitalized patients who had undergone catheter ablation. MATERIAL AND METHODS The study enrolled 575 hospitalized patients with AF who needed catheter ablation, 105 were non-first catheter ablation patients, and 470 were first catheter ablation (CA) patients. Before ablation, fasting biochemical indexes, including uTSH, were detected. Patients were classified according to uTSH quartile. The presence of AF was confirmed by 12-lead electrocardiogram or 24-h ambulatory electrocardiogram. RESULTS A total of 105 (18.44%) patients had undergone catheter ablation of AF twice or more. Univariate logistic regression analysis showed no significant relationship between uTSH and AF recurrence (HR, 1.047; 95% CI 0.986-1.111; P=1.127). Multivariate logistic regression analysis indicated that compared with low quartiles (Q1 OR, 0.71, 95% CI: 0.35-1.46; P=0.36; Q2 OR 0.71, 95% CI 0.36-1.39; P=0.31;Q3 OR 0.22, 95% CI 0.09-0.53; P=0.001), high quartiles of uTSH had a higher risk of AF recurrence. After adjusting for sex, the risk of AF recurrence in the high quartile uTSH was higher in males than in the low quartile (Q1 OR, 0.60, 95% CI: 0.29-1.26; P=0.18;Q2 OR, 0.52, 95% CI, 0.24-1.13; P=0.09;Q3 OR, 0.42, 95% CI, 0.18-0.94; P=0.03), but not in women. CONCLUSIONS Serum TSH levels in male patients treated for AF with cardiac ablation were significantly associated with AF recurrence.

Immunomodulatory Siglecs are controlled by their glycoprotein and glycolipid ligands. Siglec-glycolipid interactions are often studied outside the context of a lipid bilayer, missing the complex behaviors of glycolipids in a membrane. Through optimizing a liposomal formulation to dissect Siglec-glycolipid interactions, it is shown that Siglec-6 can recognize glycolipids independent of its canonical binding pocket, suggesting that Siglec-6 possesses a secondary binding pocket tailored for recognizing glycolipids in a bilayer. A panel of synthetic neoglycolipids is used to probe the specificity of this glycolipid binding pocket on Siglec-6, leading to the development of a neoglycolipid with higher avidity for Siglec-6 compared to natural glycolipids. This neoglycolipid facilitates the delivery of liposomes to Siglec-6 on human mast cells, memory B-cells and placental syncytiotrophoblasts. A physiological relevance for glycolipid recognition by Siglec-6 is revealed for the binding and internalization of extracellular vesicles. These results demonstrate a unique and physiologically relevant ability of Siglec-6 to recognize glycolipids in a membrane., (© 2023. The Author(s).)

Objective: To study the effect of propofol used for painless gastroscopy and colonoscopy on psychomotility recovery., Methods: One hundred adult patients undergoing painless gastroscopy and colonoscopy were recruited, aged 18-72 years, with American Society of Anesthesiologist (ASA) physical status Ⅰ-Ⅱ. According to age, the patients were divided into youth group (20-39 years old, 27 cases), middle age group (40-54 years old, 37 cases), and elder group (55-64 years old, 36 cases). Propofol was continuously infused according to the patients' condition to mantain the bispectal index (BIS) score 55-64. All the patients received psychomotility assesment 30 min before the operations when the discharge criteria were met including number cancellation test, number connection test and board test. The heart rate, blood pressure, saturation of pulse oximetry, electrocardiograph and BIS were monitored during the operation. The operating time, recovery time, total volume of propofol and discharge time were recorded. If the results obtained were inferior to those before operation, a third assessment was taken 30 minutes later until the results recovered or being superior to the baseline levels., Results: All the patients completed the first and second assessments, and 25 patients had taken the third assessment. There was no statistically significant difference in the results of psychomotility assessment when the patients met the discharge standard. Furthermore, the results were analyzed by grouping with age, and there was no statistical difference in the test results of the youth and middle age groups compared with the preoperative group, among which, the efficiency of the number cancellation test was significantly better than that before operation in the youth group ( P < 0.05). However, in the elderly patients the number cancellation efficiency, number connection test and board test were significantly inferior to that before operation ( P < 0.05). There was no significant difference in the accuracy of number cancellation compared with that before operation. The patients who needed the third test in the elder group were significantly more than in the other groups ( P < 0.05). Compared with the preoperative results, there was no statistical difference in the test results of those who completed the third test., Conclusion: The psychomotility function of the patients who underwent painless gastroscopy and colonoscopy was recovered when they met discharge criteria. The elderly patients had a prolonged recovery period.

Objective: To analyze the clinical manifestations and imaging characteristics of in vivo confocal microscopy (IVCM) for Nocardia keratitis. Methods: It was a retrospective case series study. Medical records of 16 consecutive patients (16 eyes) with Nocardia keratitis were collected from the Department of Ophthalmology at Beijing Tongren Hospital, Capital Medical University between 2018 and 2022. The group consisted of 11 males and 5 females. The inclusion criteria for the study were the presence of typical clinical manifestations of Nocardia keratitis and at least one positive pathogenic test (corneal scraping or microbial culture) indicating Nocardia infection. The medical history, clinical and microbiological examination data of the patients were analyzed, including risk factors, diagnosis time, clinical manifestations, diagnostic methods, strain isolation, cure time, and best corrected visual acuity before and after treatment. This study utilized techniques such as slit lamp microscopy, in vivo confocal microscopy (IVCM), scraping cytology, microbial culture, and mass spectrometry identification. Results: The main risk factors for Nocardia keratitis included plant or foreign body injuries (5 out of 16 cases), contact lens use (4 out of 16 cases), and surgery (2 out of 16 cases). The average time to diagnosis was (20.8±11.8) days, with the shortest time being 8 days and the longest being 60 days. The best corrected visual acuity was less than 0.05 in 7 patients, between 0.05 to 0.3 in 7 patients, and greater than or equal to 0.3 in 2 patients. The typical symptoms included superficial gray-white infiltration in a wreath-like pattern on the cornea, corneal ulcers with dry and gray-white necrotic tissue coverage, and in severe cases, corneal ulcer perforation. Nocardia corneal infection was identified in 12 out of 16 cases by scraping cytology, 9 out of 16 cases by mass spectrometry, and 8 out of 16 cases by both methods. IVCM showed the presence of fine and moderately reflective filamentous hyphae in the subepithelial and superficial stromal layer of the cornea, arranged in elongated, beaded, and branched structures. Infiltration of many hyper-reflective round inflammatory cells was also seen around the hyphae. Fourteen cases were treated with medication and 2 cases were treated with corneal transplantation. The average cure time was (37.5±25.2) days and there were no cases of recurrence during the follow-up period (all greater than 6 months). Conclusions: Nocardia keratitis is primarily characterized by dense, round, or wreath-like infiltration in the early stage, and by gray-white dry necrotic secretion and hypopyon on the surface of corneal ulcers in the middle and late stages. Fine, branched or beaded, and moderately reflective filamentous structures are the hallmark of the corneal lesion on the IVCM images.

Rapid urbanization, industrialization, and agricultural intensification have resulted in serious soil problems, such as soil acidification and cadmium pollution, affecting food security and human health. Wheat is the second largest food crop in China and has a strong accumulation capacity for cadmium. Understanding the influencing factors of cadmium content in wheat grain is crucial to realize the safe production of wheat. However, a comprehensive and quantitative analysis of how soil physicochemical properties and cultivars affect wheat cadmium accumulation is lacking. The Meta-analysis and decision tree analysis of 56 related studies published in the past 10 years showed that the proportion of cadmium content in soil and wheat grain exceeding the national standard was 52.6% and 64.1%, respectively. Among soil physical and chemical properties, pH, organic matter, available phosphorus, and total soil cadmium content were the important factors affecting the cadmium content in wheat grains. When soil pH ≤ 5.5 and 5.5-1 -1 , the proportion of cadmium content in wheat grain exceeding the national standard was the highest (61.0%). Soil pH ≥ 7.1 and total cadmium content <1.60 mg·kg -1 was suitable for wheat safety production. There were significant differences in grain cadmium content and cadmium enrichment factors among different wheat cultivars. Planting wheat cultivars with low cadmium accumulation is an economical and effective measure to decrease cadmium content in wheat grains. The current study can provide guidance for the safe production of wheat in cadmium-contaminated farmland.

A new hybrid sorbicillinoid named paeciureallin (1) and a new monomeric sorbicillinoid named paecillyketide (2), along with six known analogues (3-8), were isolated from the rhizospheric soil-derived fungus Paecilomyces sp. KMU21009 associated with Delphinium yunnanense. Their structures were elucidated by extensive spectroscopic analysis and comparison with literature values. Paeciureallin (1) is the first example of hybrid sorbicillinoids possessing a rare sorbicillinoid urea unit and containing a β-D-ribofuranose functionality. In pharmacological studies, compounds 1 and 2 were evaluated for in vitro anti-inflammatory and cytotoxic activities. Paeciureallin (1) exhibited moderate cytotoxicity against SW480 and A549 cell lines, and the IC 50 values were 32.0 ± 0.1 and 34.4 ± 2.0 μM, respectively., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aims: Fascicular ventricle tachycardia (FVT) arising from the proximal aspect of left His-Purkinje system (HPS) has not been specially addressed. Current study was to investigate its clinical, electrocardiographic, and electrophysiological characteristics., Methods and Results: Eighteen patients who were identified as this rare FVT were consecutively enrolled, and their scalar electrocardiogram and electrophysiological data were collected and analysed. The ventricular tachycardia (VT) morphology was similar to sinus rhythm (SR) in eight patients, left bundle branch block type in one patient, right bundle branch block type in seven patients, and both narrow and wide QRS type in two patients. During VT, right-sided His potential preceded the QRS with His-ventricle (H-V) interval of 36.3 ± 12.4 ms, which was shorter than that during SR (-51.4 ± 8.6 ms) (P = 0.002). The earliest Purkinje potentials (PPs) were recorded within 7 ± 3 mm of left-side His and preceded the QRS by 49.1 ± 14.0 ms. Mapping along the left anterior fascicle and left posterior fascicle revealed an antegrade activation sequence in all with no P1 potentials recorded. In the two patients with two VT morphologies, the earliest PP was documented at the same site, and the activation sequence of HPS remained antegrade. Ablation at the earliest PP successfully eliminated the tachycardia, except one patient who developed complete atrial-ventricular block and two patients who abandoned ablations. After at least 12 months follow-up, 15 patients were free from any recurrences., Conclusions: Fascicular ventricle tachycardia arising from the proximal aspect of left HPS was featured by recording slightly shorter H-V interval and absence of P1 potentials. Termination of VT requires ablation at the left-sided His or its adjacent region., Competing Interests: Conflict of interest : None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Two new trinuclear zinc(II) complexes, [Zn3I2L2(H2O)2] (1) and [Zn3(CH3OH)(DMF)L2(NCS)2] (2), where L is the dianionic form of N,N'-bis(5-bromosalicylidene)-1,2-cyclohexanediamine (H2L), have been synthesized and characterized by elemental analyses, IR and UV spectra. Structures of the complexes were further confirmed by single crystal X-ray diffraction. Both complexes are trinuclear zinc compounds. Both compounds are solvated, with water ligand for 1 and methanol ligand for 2. The outer two Zn atoms are in square pyramidal coordination, while the inner one is in octahedral coordination. The effect of the complexes on the antimicrobial activity against Staphylococcus aureus, Escherichia coli and Candida albicans were evaluated, and gave interesting results.

Background: Gastric cancer is the fourth leading cause of cancer-related deaths worldwide. And patient outcomes are poor due to tumor relapse and metastasis. To develop new therapeutic strategies, it is of great importance to explore the mechanism underlying the progression of gastric cancer., Methods: Primary gastric cancer samples with lymph node metastases (LNM) and without LNM were subjected to mRNA microarray assay. The differentially expressed genes were confirmed by RT-qPCR. HRCT1 protein expression was further detected using an immunohistochemistry (IHC) assay. In vitro and in vivo assays were performed to investigate the role of HRCT1 in tumor invasion, metastasis, and proliferation. The expressions of the downstream target genes of HRCT1 were detected by microarray, RT-qPCR and Western blot assays. Dual-luciferase reporter and Western blot assays were carried out to identify miRNAs target to HRCT1., Results: HRCT1 was upregulated in gastric cancer, and high expression of HRCT1 was associated with poor overall survival (OS) and disease-free survival (DFS). Moreover, HRCT1protein expression was an independent predictor for poor OS and DFS. HRCT1 could promote gastric cancer cells' migration, invasion, and proliferation in vitro as well as tumor metastasis and growth in vivo. Notably, our data showed that HRCT1 promoted gastric cancer progression by activating the ERBB2-MAPK signaling pathway. At least partially, the expression of HRCT1 could be negatively regulated by miR-124-3p., Conclusions: The upregulated expression of HRCT1 predicts poor survival for patients with gastric cancer. HRCT1 promotes tumor progression by activating the ERBB2-MAPK pathway. HRCT1, negatively regulated by miR-124-3p, may be a potential therapeutic target for patients with gastric cancer., (© 2023. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Objectives: The objectives of this study were to analyze the relationship between serum globulin levels and immune restoration and HIV reservoir size during long-term antiretroviral therapy (ART)., Methods: We enrolled 13 patients living with HIV who had been receiving ART for 5 years. We measured levels of serum globulin, cell-associated (CA) HIV DNA and RNA, and p24 antibody at 0, 1, 3, and 5 years of ART. CD38 and human leukocyte antigen - DR isotype (HLA-DR) were used as activation markers for T-cell activation. Serum concentrations of the inflammatory cytokines interferon gamma-inducible protein (IP)-10 and soluble CD163 (sCD163) were detected by enzyme-linked immunosorbent assay. We analyzed the relationship between serum globulin levels, HIV reservoir size, immune restoration, T-cell immune activation, and inflammatory levels during long-term ART., Results: Our data showed that serum globulin levels in people living with HIV were higher than in healthy controls and significantly decreased during the first year of ART. Serum globulin levels during long-term ART were positively correlated with CA HIV DNA, CA HIV RNA, p24 antibody levels, and CD8 + T-cell counts and negatively correlated with CD4 + T-cell counts and CD4/CD8 ratios. Moreover, serum globulin levels were positively correlated with CD4 + and CD8 + T-cell activation and the concentrations of inflammatory biomarkers IP-10 and sCD163 during long-term ART., Conclusions: Our findings suggest that serum globulin levels may be associated with HIV reservoir size and immune restoration during long-term ART., (© 2022 British HIV Association.)

Severe hypokalemia is defined as the concentration of serum potassium lower than 2.5 mmol/L, which may lead to serious arrhythmias and cause mortality. We report an unusual case of potentially fatal ventricular arrhythmias induced by severe hypokalemia in a patient undergoing laparoscopic partial nephrectomy in Peking University Third Hospital due to irregular use of indapamide before operation. Indapamide is a sulfonamide diuretic with vasodilative and calcium antagonistic effects, which enhances sodium delivery to the renal distal tubules resulting in a dose-related increase in urinary potassium excretion and decreases serum potassium concentrations. The electrolyte disorder caused by the diuretic is more likely to occur in the elderly patients, especially those with malnutrition or long-term fasting. Hence, the serum potassium concentration of the patients under indapamide therapy, especially elderly patients, should be monitored carefully. Meanwhile, the potassium concentration measured by arterial blood gas analysis is different from that measured by venous blood or laboratory test. According to the previous research, the concentration of potassium in venous blood was slightly higher than that in arterial blood, and the difference value was 0.1-0.5 mmol/L. This error should be taken into account when rapid intravenous potassium supplementation or reduction of blood potassium level was carried out clinically. In the correction of severe hypokalemia, the standard approach often did not work well for treating severe hypokalemia. The tailored rapid potassium supplementation strategy shortened the time of hypokalemia and was a safe and better treatment option to remedy life-threatening arrhythmias caused by severe hypokalemia with a high success rate. Through the anesthesia management of this case, we conclude that for the elderly patients who take indapamide or other potassium excretion diuretics, the electrolyte concentration and the general volume state of the patients should be comprehensively measured and fully evaluated before operation. It may be necessary for us to reexamine the serum electrolyte concentration before anesthesia induction on the morning of surgery in patients with the history of hypokalemia. For severe hypokalemia detected after anesthesia, central venous cannulation access for individualized rapid potassium supplementation is an effective approach to reverse the life-threatening arrhythmias caused by severe hypokalemia and ensure the safety of the patients.

BACKGROUND This study from a single center in Beijing, China, included 412 patients with atrial fibrillation (AF) who underwent radiofrequency catheter ablation. We aimed to determine whether pre-ablation serum lipid levels were related to recurrence of atrial fibrillation (RAF). MATERIAL AND METHODS A total of 412 patients with AF who underwent radiofrequency catheter ablation were enrolled in the study. Fasting levels of triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC), were measured at baseline before ablation, and patients were classified according to lipid level quartiles (Q1-Q4). RAF was affirmed via 24-h electrocardiography or 12-lead electrocardiography. RESULTS A total of 82 (19.90%) patients experienced RAF. After adjusting for other relevant factors and sex, univariate logistic regression analysis revealed LDL-C (hazard ratio [HR], 1.17; 95% confidence interval [CI], 0.93-1.47) and TC (HR, 1.17; 95% CI, 0.96-1.42) levels were not significantly related to RAF. Multivariate logistic regression analysis revealed that, compared with the highest quartile (Q4), female patients with lower quartiles of TC had higher RAF, especially Q3 (HR, 16.24; 95% CI, 1.14-231.56). LDL-C levels were higher in Q1 than in Q4 but lower in Q2 and Q3 than in Q4 (Q1: HR, 1.34; 95% CI, 0.08-18.89; Q2: HR, 0.09, 95% CI, 0.06-1.52; Q3: HR, 0.02, 95% CI, 0.14-0.57). CONCLUSIONS This study showed RAF in almost 20% of treated patients and RAF was significantly related to pre-ablation serum levels of LDL-C and TC in women.

Background: Anorectal diseases are common in the population and include internal, external, and mixed hemorrhoids. Although hemorrhoid surgery is a brief operation, anesthesia, anesthetic drugs, drug concentrations, and anesthesia level control are closely related to postoperative uroschesis. For hemorrhoid surgery, a single spinal block with ropivacaine is commonly used that blocks the S2-S4 parasympathetic nervous system, which in turn governs the voiding reflex, causing postoperative urinary retention; this affects the recovery of patients. This study was performed to investigate the effects of two doses ropivacaine that provided satisfactory analgesia and muscle relaxation and inhibited adverse reflexes on urinary retention after hemorrhoidectomy., Methods: The study included 200 male patients who underwent anorectal surgery with American Society of Anesthesiologists (ASA) grade I-II single elective spinal anesthesia between March 2021 and March 2022. Patients were randomly assigned to 2 groups using a random number table: Group A ( n  = 100) received 10 mg 0.5% ropivacaine (1.5 ml 1% ropivacaine + 1.5 ml 10% glucose = 3 ml), and Group B ( n  = 100) received 15 mg 0.5% ropivacaine (1.5 ml 1% ropivacaine + 1.5 ml 10% glucose = 3 ml)., Results: The anal sphincter exhibited good relaxation, and no obvious traction pain or significant difference in the time of muscle strength recovery was observed between the 10 mg and 15 mg 0.5% ropivacaine groups ( P  > 0.05). The 10 mg 0.5% ropivacaine group had shorter time of micturition exceeding 100 ml and lower voiding International Prostate Symptom Score than the 15 mg 0.5% ropivacaine group ( P  < 0.01)., Conclusions: Single spinal anesthesia with 10 mg 0.5% ropivacaine not only provides satisfactory anesthetic effect for hemorrhoidectomy but also has less influence on postoperative uroschesis and is worthy of clinical application., Trial Registration: The study was registered in the Chinese Clinical Trial Registry (http://www.chictr.org.cn; identifier: ChiCTR2,100,043,686) on February 27, 2021., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Wang, Kang, Duan, Chang, Li, Guo, Kang and Han.)

Objective: In addition to significantly reducing breast cancer recurrence risk, radiotherapy also prolongs patients' lives. However, radiotherapy-related genes and biomarkers still remain poorly understood. The present study aimed to identify radiation-associated genes in breast cancer., Materials and Methods: Breast cancer data were downloaded from Gene Expression Omnibus (GEO) and UCSC Xena database. The gene ontology (GO) enrichment and gene set enrichment analysis (GSEA) were performed for annotation and integrated discovery. Protein-protein interaction (PPI) network was constructed by STRING database and hub genes were identified. Then, immunohistochemistry and tissue expression of key genes was analyzed by using the Human Protein Atlas (HPA) and GEPIA database. Genes associated with prognosis were identified by performing univariate cox analysis., Results: We identified 341 differentially expressed genes related to radiotherapy in breast cancer patients. PPI analysis revealed a total of 129 nodes and 516 interactions and identified five hub genes (EGFR, FOS, ESR1, JUN, and IL6). In addition, 11 SDEGs THBS1, SERPINA11, NFIL3, METTL7A, KCTD12, HSPA6, EGR1, DDIT4, CCDC3, C11orf96, and BCL2A1 candidate genes can be used as potential diagnostic markers. The calibration curve and ROC indicate good probability consistencies of 3-years and 5-year survival rates of patients between estimation and observation., Conclusions: Our findings provide novel insight into the functional characteristics of breast cancer through integrative analysis of GEO data and suggest potential biomarkers and therapeutic targets for breast cancer.

Background: Conventional magnetic resonance imaging (MRI) techniques cannot demonstrate microvascular alterations in mild Alzheimer's disease (AD). Thus, the diagnosis of microvascular pathology commonly relies on postmortem. The purpose of this study was to evaluate alterations of microvascular structures in patients with AD using a 3T clinical MRI system with a commercially available contrast agent., Methods: Eleven patients with AD and 11 cognitively normal (CN) controls were included in this cross-sectional prospective study. R2 and R2* relaxation rate changes (∆R2 and ∆R2*) before and after a Gadolinium (Gd)-based contrast agent injection were calculated from images obtained with a multi-echo turbo spin-echo sequence and multi-echo gradient-echo sequence to obtain microvascular index maps of blood volume fraction (BVf), mean vessel diameter (mVD), vessel size index (VSI), mean vessel density (Q), and microvessel-weighted imaging (MvWI). Two-sample t -test was used to compare those values between the two groups. Correlation analysis was performed to evaluate the relationship between those values and age., Results: BVfs at the corpus callosum and at the thalamus were significantly increased in the AD group (P=0.024 and P=0.005, respectively). BVf at the gray matter (P=0.020) and white matter area (P=0.012) were also significantly increased in the AD group compared with the CN group. MvWIs at the hippocampus and parahippocampal gyrus were significantly increased in the AD group compared with the CN group (P=0.020 and P=0.006, respectively). Voxel-based analysis showed both mVD and VSI were significantly decreased at the prefrontal lobe in the AD group. Q were not significant difference between CN and AD groups. MvWI were significantly positively correlated with age., Conclusions: Microvascular index was a useful non-invasive method to evaluate microvascular morphology alteration. The microvascular morphology of AD was manifested as increasing BVf and microvessel-weighted., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-22-524/coif). The authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Droplet rebound from hydrophobic leaves is a major factor influencing pesticide utilization. The use of a surfactant is a major strategy to reduce droplet rebound, promoting pesticide deposition on hydrophobic agricultural plant leaves. However, most surfactants known to regulate droplet rebound are either anionic or cationic. In this study, ethoxylated propoxylated 2-ethyl-1-haxanol (EH 6) was identified as a nonionic surfactant that inhibits droplet rebound while promoting the complete spreading of the droplet on hydrophobic leaves. Compared with the widely reported nonionic surfactant Tween 20, EH 6 performs better at concentrations above 0.3%. This phenomenon can be attributed to the rapid migration of EH 6 from the bulk to the newly generated interface, significantly reducing the surface tension. We introduce a simple and effective strategy that can be used to enhance droplet deposition on hydrophobic plant surfaces, which may offer future economic and environmental benefits., 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 © 2022 Elsevier Inc. All rights reserved.)

Zinc finger protein 671 (ZNF671) has been described as a vital cancer inhibitor in multiple neoplasms, yet the functional roles of ZNF671 in colorectal carcinoma (CRC) remain unresolved. This project examined the possible link between ZNF671 and CRC. Lower levels of ZNF671 were observed in CRC tissue compared with noncancerous tissue, which were related to a worse survival rate in CRC patients. High methylation levels at the ZNF671 gene promoter region were shown in CRC tissue, which were inversely correlated with ZNF671 expression. Treatment with demethylation agents restored ZNF671 levels in CRC cell lines. Up-regulation of ZNF671 resulted in suppressive effects on the proliferative ability and metastatic potency of CRC cells. Moreover, the up-regulation of ZNF671 reinforced the chemosensitivity of CRC cells. A mechanism study determined ZNF671 to be a vital mediator of Notch signaling. The up-regulation of ZNF671 decreased the expression of Notch1 and lowered the levels of NICD, HES1, and HEY1. The overexpression of NICD1 diminished ZNF671-mediated antitumor effects. ZNF671 depletion reinforced Notch signaling, and Notch suppression reversed ZNF671-depletion-elicited protumor effects. Moreover, the overexpression of ZNF671 weakened the tumorigenicity of CRC cells in a xenograft model in vivo. In summary, ZNF671 exerts a cancer-inhibiting function in CRC via the deactivation of Notch signaling. Low ZNF671 levels caused by gene promoter hypermethylation contribute to the malignant transformation of CRC. This work underlines the interest of ZNF671 as a target candidate for exploiting novel anti-CRC therapies., Competing Interests: Declaration of Competing Interest All authors have no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Perimitral atrial tachycardia (PMAT) is the most frequent type of iatrogenic atrial tachycardia (AT) after atrial fibrillation (AF) ablation. Vein of Marshall ethanol infusion (EIVOM) is a promising technique in mitral isthmus (MI) ablation., Methods: A total of 165 patients with PMAT were divided into three groups according to ablation strategies, including RF only group (n = 89), RF-EIVOM group (initial RF ablation with adjunctive EIVOM, n = 28), and EIVOM-RF group (first-step EIVOM with touch-up RF ablation, n = 48). Acute and follow-up procedure outcomes were evaluated., Results: PMAT terminated in 89.9%, 89.3%, and 93.7% of patients in RF only, RF-EIVOM and EIVOM-RF groups, respectively (p = .715), with complete MI block achieved in 80.9%, 89.3%, and 95.8% of patients (EIVOM-RF vs. RF only, p = .012). First-step utilization of EIVOM was associated with a significant shortening of RF ablation time at MI (EIVOM-RF 2.1 ± 1.3 min, RF only 7.9 ± 5.9 min, RF-EIVOM 6.8 ± 5.8 min; p < .001) and a decrease in the proportion of patients need ablation within coronary sinus (CS, EIVOM-RF 14.6%, RF only 61.8%, RF-EIVOM 64.3%; p < .001). After a mean follow-up of 12.1 ± 6.2 months, AF/AT recurred in 39 (43.8%), 6 (21.4%), and 12 (25.0%) patients in RF only, RF-EIVOM, and EIVOM-RF group (RF-EIVOM vs. RF only, p = .026; EIVOM-RF vs. RF only, p = .022)., Conclusions: EIVOM was associated with an enhanced acute MI block rate as well as reduced AF/AT recurrence. First-step utilization of EIVOM promises to significantly simplify the RF ablation process., Condensed Abstract: PMAT is the most common type of iatrogenic AT after AF ablation procedures. EIVOM contributed to a higher acute MI block rate and lower arrhythmia recurrence risk during follow-up. First-step utilization of EIVOM significantly reduced the need for radiofrequency ablation at MI and inside CS with the advantage of creating a homogenous, transmural lesion and eliminating epicardial connections., (© 2022 Wiley Periodicals LLC.)

A series of hydrazones, (E)-N'-(4-hydroxy-3-methoxybenzylidene)-4-nitrobenzohydrazide (1), (E)-4-(dimethylamino)-N'-(4-hydroxy-3-methoxybenzylidene)benzohydrazide (2), N'-(2-hydroxy-5-methylbenzylidene)-4-nitrobenzohydrazide (3) and 2-fluoro-N'-(2-hydroxy-5-methylbenzylidene)benzohydrazide (4), were prepared and structurally characterized by elemental analysis, IR and 1H NMR spectra, and X-ray single crystal determination. The xanthine oxidase inhibitory activities of the compounds were investigated. Among the compounds, N'-(3-methoxybenzylidene)-4-nitrobenzohydrazide (1) showed the strongest activity. Docking simulations were performed to insert the compounds into the crystal structure of xanthine oxidase at the active site and to investigate the probable binding modes.

It is known that neurotrophic factors are a major source of the neuroprotective effects of olfactory ensheathing cells (OECs). However, the form of neurotrophic factors that originate from OECs is not fully understood. Our previous study demonstrated that OECs could secrete exosome (OECs-Exo), which provided neuroprotection by switching the phenotype of macrophages/microglia. Considering that exosomes could also be taken up by neurons, we explored the direct effect of OECs-Exo on neuronal survival and the underlying mechanism. Electron microscopy, nano-traffic analysis, and Western blotting were applied to identify the OECs-Exo. The effect of OECs-Exo on neuronal survival was tested by flow cytometry and TUNEL staining. Western blotting and ELISA were used to detect neurotrophic factors in purified OECs-Exo. We first isolated OECs-Exo and found that OECs-Exo exerted protective effects on neuronal survival in response to TNF-α challenge. Brain-derived neurotrophic factor (BDNF) was then identified in OECs-Exo, and its receptor TrkB in neurons was activated by OECs-Exo treatment. Furthermore, we demonstrated that OECs prevented TNF-α-induced apoptosis in neurons partially through exosome-derived BDNF. Our data showed that OECs attenuated TNF-α-induced apoptosis in neurons partially through OEC-Exo-derived BDNF, which might provide a novel strategy for the neuroprotective effect of OEC-Exo-based treatment., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Debates exist in the repeat ablation strategy for patients with recurrence presenting as persistent atrial fibrillation (AF) after initial persistent AF ablation., Objective: To compare the outcome between the "2C3L" and "extensive ablation" approach in patients undergoing repeat procedures for recurrent persistent AF., Methods: Propensity-score matching was performed in 196 patients with AF recurrence undergoing repeat ablation, and 79 patients treated with "2C3L" strategy were matched to 79 patients treated with "extensive ablation" strategy. The "2C3L" approach included pulmonary vein isolation, mitral isthmus, left atrial roof, and cavotricuspid isthmus ablation, while the "extensive ablation" strategy included extensive ablation of a variety of other targets aiming to terminate the AF. The primary outcome was freedom from any atrial tachyarrhythmia after 24-h ambulatory monitoring follow-up for 12 months., Results: No statistically significant difference was found between the primary outcome between the "2C3L" and the "extensive ablation" group [70.9% vs. 69.6%, p = .862; 95% confidence interval (CI) -12.8 to 15.3], although the "extensive ablation" group had a significantly high proportion of AF termination (19.0% for "2C3L" vs. 41.8% for "extensive ablation" group, p = .002; 95% CI 8.5-35.9). And AF termination was not related to the primary outcome in multifactorial regression. At 40 ± 22 months after the repeat procedure, the primary outcome was also comparable (57.0 % for "2C3L" vs. 48.1% for "extensive ablation" group, p = .265; 95% CI -6.6 to 23.7)., Conclusion: The outcome between the "2C3L" and "extensive ablation" approaches was comparable in patients undergoing repeat procedures for recurrent persistent AF., (© 2022 Wiley Periodicals LLC.)

Nine patients identified as hypertrophic obstructive cardiomyopathy (HOCM) in Beijing Anzhen Hopspital who underwent ablation from March to July 2019 were included in the study. All patients had left ventricular outflow tract gradient (LVOTG) over 50 mmHg(1 mmHg=0.133 kPa)with significant symptoms despite not optimal drug therapy. Intracardiac echocardiography (ICE) was used to reconstruct septum and surrounding structures, and monitor the effect of ablation during procedure. Nine patients with HOCM were included,.of which 6 men and 3 women. The average age was (51.7±12.2) years. All patients underwent successful ablation after a mean of procedural time of (152.2±31.9) minutes and ablation time of (838.4±227.3) seconds. Except for one patients, all other patients had significant LVOTG reduction( P= 0.001)within 50 mmHg after the procedure. Systolic anterior motion of the mitral valve disappeared in all patients after the procedure without major periprocedural complications. The LVOTG of these patients remained stable during follow-up. Radiofrequency ablation using ICE guidance is feasible in treating HOCM with promising efficacy and safety.

A search for exotic dark matter (DM) in the sub-GeV mass range has been conducted using 205 kg day data taken from a p-type point contact germanium detector of the CDEX-10 experiment at China's Jinping underground laboratory. New low-mass dark matter searching channels, neutral current fermionic DM absorption (χ+A→ν+A) and DM-nucleus 3→2 scattering (χ+χ+A→ϕ+A), have been analyzed with an energy threshold of 160 eVee. No significant signal was found; thus new limits on the DM-nucleon interaction cross section are set for both models at the sub-GeV DM mass region. A cross section limit for the fermionic DM absorption is set to be 2.5×10^{-46}  cm^{2} (90% C.L.) at DM mass of 10  MeV/c^{2}. For the DM-nucleus 3→2 scattering scenario, limits are extended to DM mass of 5 and 14  MeV/c^{2} for the massless dark photon and bound DM final state, respectively.

We present improved germanium-based constraints on sub-GeV dark matter via dark matter-electron (χ-e) scattering using the 205.4  kg·day dataset from the CDEX-10 experiment. Using a novel calculation technique, we attain predicted χ-e scattering spectra observable in high-purity germanium detectors. In the heavy mediator scenario, our results achieve 3 orders of magnitude of improvement for m&#95;{χ} larger than 80  MeV/c^{2} compared to previous germanium-based χ-e results. We also present the most stringent χ-e cross-section limit to date among experiments using solid-state detectors for m&#95;{χ} larger than 90  MeV/c^{2} with heavy mediators and m&#95;{χ} larger than 100  MeV/c^{2} with electric dipole coupling. The result proves the feasibility and demonstrates the vast potential of a new χ-e detection method with high-purity germanium detectors in ultralow radioactive background.

Photoreactive coordination polymers are particularly important media for the implementation of highly-selective photoreactions and creation of photoresponsive intelligent materials and devices. Herein, a two-dimensional (2D) photoreactive coordination polymer, formulated as [Cd(pha)(3,3'-bpe)] n (1) was prepared through the hydrothermal reaction between Cd(NO 3 ) 2 ·4H 2 O, phthalic acid (H 2 pha) and 1,2-bis(3-pyridyl)ethylene (3,3'-bpe). Upon exposure to 365 nm UV light, the 1 H NMR spectroscopy and single crystal X-ray diffraction analysis results indicated that 1 can undergo a [2 + 2] photocycloaddition reaction and thus form a new coordination polymer [Cd(pha)(3,3'-tpcb) 0.5 ] n (1a) through single-crystal to single-crystal (SCSC) transformation. Accompanied by the SCSC photoreaction, the 2D sql net of 1 converted into a 2D binodal network of 1a with the rare (3 2 4·6 2 7)(3 2 6 2 7 2 ) topology. The SCSC transformation from 1 to 1a also exhibits an interesting photocontrolled fluorescence. The unique photoinduced structural change and fluorescence quenching of 1 makes it a potential intelligent material for optical anti-counterfeiting, fluorescence sensors and other fields.

Breast cancer (BC) is the most common malignant tumor in women worldwide. Metastasis is the main cause of BC-related death. The specific mechanism underlying BC metastasis remains obscure. Recently, PRSS22 was discovered to be involved in tumor development, however, its detailed biological function and regulatory mechanism in BC are unclear. Here, we characterized that PRSS22 expression is upregulated in BC tissues compared with non-tumorous breast tissues. Dual luciferase assays, bioinformatics analyses and chromatin immunoprecipitation (ChIP) assays indicated that transcription factor E2F1 directly binds to the PRSS22 promoter region and activates its transcription. Functionally, upregulation of PRSS22 promoted invasion and metastasis of BC cells in vitro and in vivo, whereas knockdown of PRSS22 inhibited its function. Mechanistically, the combination of PRSS22 and ANXA1 protein in BC cells was first screened by protein mass spectrometry analysis, and then confirmed by co-immunoprecipitation (Co-IP) and western blot assays. Co-overexpression of PRSS22 and ANXA1 could promote BC cell migration and invasion. We further demonstrated that PRSS22 promotes the cleavage of ANXA1 and in turn generates an N-terminal peptide, which initiates the FPR2/ERK signaling axis to increase BC aggressiveness., (© 2022. The Author(s).)

Myocardial ischemia/reperfusion (I/R) injury is associated with the poor outcome and higher mortality after myocardial infarction. Recent studies have revealed that miR-199a-5p participates in the process of myocardial I/R injury, but the precise roles and molecular mechanisms of miR-199a-5p in myocardial I/R injury remain not well-studied. Ferroptosis has been proposed to promote cardiomyocyte death, closely associated with myocardial I/R injury. Herein, the present study aimed to explore the function and mechanisms by which miR-199a-5p regulates whether miR-199a-5p contributes to ferroptosis-induced cardiomyocyte death responding to oxygen-glucose deprivation/reoxygenation (OGD/R) injury, an in vitro model of myocardial I/R injury focusing on Akt/eNOS signaling pathway. The results found that ferroptosis-induced cardiomyocyte death occurs and is accompanied by an increase in miR-199a-5p level in OGD/R-treated H9c2 cells. MiR-199a-5p inhibitor ameliorated ferroptosis-induced cardiomyocyte death as evidenced by the increased cell viability, the reduced reactive oxygen species (ROS) generation, lactate dehydrogenase (LDH) activity, malondialdehyde (MDA) and Fe 2+ contents, and the up-regulated glutathione (GSH)/glutathione disulphide (GSSG) ratio as well as glutathione peroxidase 4 (Gpx4) protein expression in H9c2 cells-exposed to OGD/R, while miR-199a-5p mimic had the opposite effects. In addition, OGD/R led to the inhibition of Akt/eNOS signaling pathway, which was also blocked by miR-199a-5p inhibitor and aggravated by miR-199a-5p mimic. Furthermore, LY294002, an inhibitor of Akt/eNOS signaling pathway, abrogated miR-199a-5p inhibitor-induced the reduction of ferroptosis-induced cardiomyocyte death. In summary, our findings demonstrated that miR-199a-5p plays a central role in stimulating ferroptosis-induced cardiomyocyte death during ischemic/hypoxic injury via inhibiting Akt/eNOS signaling pathway., (© 2022 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Background: Very preterm infants often require mechanical ventilation. However, objective criteria to predict the outcomes of extubation in very premature neonates remain lacking. The aim of this study was to investigate the accuracy of the spontaneous breathing trial (SBT) using a combined model of continuous positive airway pressure (CPAP) and low-level pressure support ventilation (PSV) to predict the extubation outcomes of preterm infants with gestational age < 32 weeks., Methods: Preterm infants with gestational age < 32 weeks, birth weight < 1500 g and requiring mechanical ventilation were selected for the study. All infants underwent a 10-minute SBT using CPAP combined with low-level PSV prior to the planned extubation. Then, the infants were extubated within 1 h after SBT. The outcomes of extubation were considered successful if the neonates did not require reintubation 72 h after extubation., Results: A total of 119 eligible preterm infants were enrolled in the study, with a median gestational age of 28.9 (27.1-30.3) weeks and a median birth weight of 1100 (900-1350) g. In total, 101 of all infants had successful extubation, 18 of whom failed and eventually had to be reintubated. Of the 102 infants who achieved SBT, 99 were successfully extubated, and 15 of the 17 infants who did not pass SBT had failed extubation. Finally, the diagnostic value for SBT could be assessed with a sensitivity of 98%, a specificity of 83.3%, a positive predictive value of 97.1% and a negative predictive value of 88.2%., Conclusion: SBT using a combined CPAP + low-level PSV model can predict the outcomes of extubation in very preterm infants with high sensitivity and specificity., (© 2022. The Author(s).)

Since the birth of cyanidation, it has been dominant in the gold extraction industry. Recently, with the increasing awareness of environmental hazards and potential risks posed by the severe toxicity of cyanide, attempts to seek alternative lixiviants have arisen. Over the past three decades, a significant amount of literature has examined alternative lixiviants to cyanide for recovering gold, while few industrial applications have been reported due to various obstacles, such as toxicity, excessive consumption, or low leaching efficiency. These obstacles are progressively overcome in multiple ways, including process improvement, system optimization, use of co-intensifying systems, and development of additives. In this paper, related studies about alternative lixiviants and methods such as cyanide, thiosulfate, thiourea, thiocyanate, polysulfides, halides, and microbial leaching are summarized. The history, fundamentals, advancements, and challenges of alternative lixiviants are fully concluded to provide a reference for cleaner gold production. In addition, the comprehensive performance of lixiviants was evaluated according to a novel evaluation criterion proposed in terms of economy, efficiency, and environment., 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 © 2022 Elsevier B.V. All rights reserved.)

Operator spreading, often characterized by out-of-time-order correlators (OTOCs), is one of the central concepts in quantum many-body physics. However, measuring OTOCs is experimentally challenging due to the requirement of reversing the time evolution of systems. Here we apply Floquet engineering to investigate operator spreading in a superconducting 10-qubit chain. Floquet engineering provides an effective way to tune the coupling strength between nearby qubits, which is used to demonstrate quantum walks with tunable couplings, reversed time evolution, and the measurement of OTOCs. A clear light-cone-like operator propagation is observed in the system with multiple excitations, and has a nearly equal velocity as the single-particle quantum walk. For the butterfly operator that is nonlocal (local) under the Jordan-Wigner transformation, the OTOCs show distinct behaviors with (without) a signature of information scrambling in the near integrable system.

Objective: Paeoniae Radix Rubra (PRR) is a commonly used traditional Chinese medicine with the effects of clearing away heat, cooling the blood, and relieving blood stasis. To 1) elucidate the metabolites and metabolic pathways of PRR and its 14 main constituents in mice and 2) reveal the possible origins of the known effective forms of PRR and their isomers, the metabolism of PRR in mice was systematically studied for the first time. Methods: PRR and its 14 constituents were administered to mice by gavage once a day for seven consecutive days, respectively. All urine and feces were collected during the 7 days of dosing, and blood was collected at 1 h after the last dose. Metabolites were detected and identified using high performance liquid chromatography with diode array detector and combined with electrospray ionization ion trap time-of-flight multistage mass spectrometry (HPLC-DAD-ESI-IT-TOF-MS n ). Results: In total, 23, 16, 24, 17, 18, 30, 27, 17, 22, 17, 33, 3, 8, 24, and 31 metabolites of paeoniflorin, albiflorin, oxypaeoniflorin, benzoylpaeoniflorin, hydroxybenzoylpaeoniflorin, benzoyloxypaeoniflorin, galloylpaeoniflorin, lactiflorin, epicatechin gallate, catechin gallate, catechin, ellagic acid, 3,3'-di- O -methylellagic acid, methylgallate, and PRR were respectively identified in mice; after eliminating identical metabolites, a total of 195 metabolites remained, including 8, 11, 25, 17, 18, 30, 27, 17, 21, 17, 1, 2, 8, 20, and 20 newly identified metabolites, respectively. The metabolic reactions of PRR and its 14 main constituents in mice were primarily methylation, hydrogenation, hydrolysis, hydroxylation, glucuronidation, and sulfation. Conclusion: We elucidated the metabolites and metabolic pathways of PRR and its 14 constituents (e.g., paeoniflorin, catechin, ellagic acid, and gallic acid) in mice and revealed the possible origins of the 10 known effective forms of PRR and their isomers. The findings are of great significance to studying the mechanism of action and quality control of PRR., 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, Lv, Zhang, Shi, Guo, Xu, Wang, Chen, Xiang, Xu, Wang and Cai.)

Characterization of the dynamic change in the immunological landscape during malignant transformation from precancerous lesions to cancerous lesions in squamous cell carcinoma (SCC) is critical for the application of immunotherapy. Here, we performed single-cell RNA-Seq (scRNA-Seq) of 131,702 cells from 13 cancerous tissues of oral squamous cell carcinoma (OSCC), 3 samples of precancerous oral leukoplakia, and 8 adjacent normal samples. We found that tumor-infiltrating CD4+ and CD8+ T cells were functionally inhibited by immunosuppressive ligands expressed on various types of myeloid cells or neutrophils in the process of oral carcinogenesis. Notably, we identified a subset of myofibroblasts that exclusively expressed tryptophan 2,3-dioxygenase (TDO2). These TDO2+ myofibroblasts were located distally from tumor nests, and both CD4+ and CD8+ T cells were enriched around them. Functional experiments revealed that TDO2+ myofibroblasts were more likely to possess the ability for chemotaxis toward T cells but induced the transformation of CD4+ T cells into Tregs and caused CD8+ T cell dysfunction. We further showed that use of the TDO2 inhibitor LM10 attenuated the inhibitory states of T cells, restored the T cell antitumor response, and prevented the progression of OSCC malignant transformation in murine models. Our study reveals a multistep transcriptomic landscape of OSCC and demonstrates that TDO2+ myofibroblasts are potential targets for immunotherapy.

Background: Acute pericardial tamponade (APT) is one of the most serious complications of catheter ablation for atrial fibrillation (AF-CA). Direct autotransfusion (DAT) is a method of reinjecting pericardial blood directly into patients through vein access without a cell-salvage system. Data regarding DAT for APT are rare and provide limited information. Our present study aims to further investigate the safety and feasibility of DAT in the management of APT during the AF-CA procedure., Methods and Results: We retrospectively reviewed 73 cases of APT in the perioperative period of AF-CA from January 2014 to October 2021 at our institution, among whom 46 were treated with DAT. All included patients successfully received emergency pericardiocentesis through subxiphoid access guided by X-ray. Larger volumes of aspirated pericardial blood (658.4 ± 545.2 vs. 521.2 ± 464.9 ml), higher rates of bridging anticoagulation (67.4 vs. 37.0%), and surgical repair (6 vs. 0) were observed in patients with DAT than without. Moreover, patients with DAT were less likely to complete AF-CA procedures (32/46 vs. 25/27) and had a lower incidence of APT first presented in the ward (delayed presentation) (8/46 vs. 9/27). There was no difference in major adverse events (death/disseminated intravascular coagulation/multiple organ dysfunction syndrome and clinical thrombosis) (0/0/1/0 vs. 1/0/0/0), other potential DAT-related complications (fever/infection and deep venous thrombosis) (8/5/2 vs. 5/3/1), and length of hospital stay (11.4 ± 11.6 vs. 8.3 ± 4.7 d) between two groups., Conclusion: DAT could be a feasible and safe method to deal with APT during AF-CA procedure., 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 Zhao, Liu, Su, Long, Sang, Tang, Yu, Liu, Jiang, Li, Guo, Wang, Zuo, Dong and Ma.)

The ^{13}C(α,n)^{16}O reaction is the main neutron source for the slow-neutron-capture process in asymptotic giant branch stars and for the intermediate process. Direct measurements at astrophysical energies in above-ground laboratories are hindered by the extremely small cross sections and vast cosmic-ray-induced background. We performed the first consistent direct measurement in the range of E&#95;{c.m.}=0.24 to 1.9 MeV using the accelerators at the China Jinping Underground Laboratory and Sichuan University. Our measurement covers almost the entire intermediate process Gamow window in which the large uncertainty of the previous experiments has been reduced from 60% down to 15%, eliminates the large systematic uncertainty in the extrapolation arising from the inconsistency of existing datasets, and provides a more reliable reaction rate for the studies of the slow-neutron-capture and intermediate processes along with the first direct determination of the alpha strength for the near-threshold state.

Background Context: Low back pain, affecting nearly 40% of adults, mainly results from intervertebral disc degeneration (IVDD), while the pathogenesis of IVDD is still not fully elucidated. Recently, some researches have revealed that necroptosis, a programmed necrosis, participated in the progression of IVDD, nevertheless, the underlying mechanism remains unclear., Purpose: To study the mechanism of necroptosis of Nucleus Pulposus (NP) cells in IVDD, focusing on the role of MyD88 signaling., Study Design: The expression and co-localization of necroptotic indicators and MyD88 were examined in vivo , and MyD88 inhibitor was applied to determine the role of MyD88 signaling in necroptosis of NP cells in vitro ., Methods: Human disc specimens were collected from patients receiving diskectomy for lumbar disc herniation (LDH) or traumatic lumbar fractures after MRI scanning. According to the Pfirrmann grades, they were divided into normal (Grades 1, 2) and degenerated groups (4, 5). Tissue slides were prepared for immunofluorescence to assess the co-localization of necroptotic indicators (RIP3, MLKL, p-MLKL) and MyD88 histologically. The combination of TNFα, LPS and Z-VAD-FMK was applied to induce necroptosis of NP cells. Level of ATP, reactive oxygen species (ROS), live-cell staining and electron microscope study were employed to study the role of MyD88 signaling in necroptosis of NP cells., Results: In vivo , the increased expression and co-localization of necroptotic indicators (RIP3, MLKL, p-MLKL) and MyD88 were found in NP cells of degenerated disc, while very l low fluorescence intensity in tissue of traumatic lumbar fractures. In vitro , the MyD88 inhibitor effectively rescued the necroptosis of NP cells, accompanied by increased viability, ATP level, and decreased ROS level. The effect of MyD88 inhibition on necroptosis of NP cells was further confirmed by ultrastructure of mitochondria shown by Transmission Electron Microscope (TEM)., Conclusion: Our results indicated that the involvement of MyD88 signaling in the necroptosis of NP cells in IVDD, which will replenish the pathogenesis of IVDD and provide a novel potential therapeutic target for IVDD., 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 Fan, Chen, Tang, Shan, Chen, Liu, Zhang, Guo, Yang and Hao.)

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease, associated with an outcome of hepatic fibrosis/cirrhosis and hepatocellular carcinoma. However, limited exploration of the underlying mechanisms hinders its prevention and treatment. To investigate the mechanisms of epigenetic regulation in NAFLD, the expression profile of circular RNA (circRNA) of rodents in which NAFLD was induced by a high-fat, high-cholesterol (HFHC) diet was studied. Modeling of the circRNA-microRNA (miRNA) -mRNA regulatory network revealed the functional characteristics of NAFLD-specific circRNAs. The targets and effects in the liver of such NAFLD-specific circRNAs were further assessed. Our results uncovered that the downregulation of 28 annotated circRNAs characterizes HFHC diet-induced NAFLD. Among the downregulated circRNAs, long intergenic non-protein coding RNA, P53 induced transcript (LNCPINT) -derived circRNAs (circ&#95;0001452, circ&#95;0001453, and circ&#95;0001454) targeted both miR-466i-3p and miR-669c-3p. Their deficiency in NAFLD abrogated the circRNA-based inhibitory effect on both miRNAs, which further inactivated the AMPK signaling pathway via AMPK-α1 suppression. Inhibition of the AMPK signaling pathway promotes hepatic steatosis, depending on the transcriptional and translational upregulation of lipogenic genes, such as those encoding sterol regulatory element-binding protein 1 (SREBP1) and fatty acid synthase (FASN) in hepatocytes. The levels of LNCPINT-derived circRNAs displayed a negative association with hepatic triglyceride (TG) concentration. These findings suggest that loss of LNCPINT-derived circRNAs may underlie NAFLD via miR-466i-3p- and miR-669c-3p-dependent inactivation of the AMPK signaling pathway., 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 Xie, Cao, Guo, Guo, He, Xu, Shen and Pan.)

A novel series of 2-(2- oxoethyl)pyrimidine-5-carboxamide derivatives were designed, synthesized and evaluated as acetylcholinesterase inhibitors (AChEIs) for the treatment of Alzheimer's disease (AD). Biological activity results demonstrated that compound 10q showed the best inhibitory activity against AChE (IC 50  = 0.88 ± 0.78 μM), which was better than that of Huperzine-A, and its inhibitory effect on BuChE was weak (IC 50  = 10.0 ± 1.30 μM), which indicated that compound 10q was a dominant AChE inhibitor. In addition, the result of molecular docking study displayed that 10q could simultaneously bind to CAS and PAS sites of AChE, which was consistent with the mixed inhibition mode shown by the enzymatic kinetics study of 10q. Furthermore, the molecular properties of the target compounds were predicted online using the molinspiration server and pkCSM, The results exhibited that compound 10q had drug-like properties that satisfied the Lipinski's rule of five. Based on the bioactivity and molecular properties, compound 10q for further development was valuable., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Hyperuricemia can induce acute and chronic kidney damage, but the pathological mechanism remains unclear. The potential role of AMP-activated protein kinase (AMPK) α2 in hyperuricemia-induced renal injury was investigated in this study. Acute and chronic hyperuricemic nephropathy was induced by administering intraperitoneal injections of uric acid and oxonic acid to AMPK α2 knockout and wild-type mice. Changes in renal function, histopathology, inflammatory cell infiltration, renal interstitial fibrosis, and urate deposition were analyzed. In both acute and chronic hyperuricemic nephropathy mouse models, knockout of AMPK α2 significantly reduced serum creatinine levels and renal pathological changes. The tubular expression of kidney injury molecule-1 was also reduced in hyperuricemic nephropathy mice deficient in AMPK α2. In addition, knockout of AMPK α2 significantly suppressed the infiltration of renal macrophages and progression of renal interstitial fibrosis in mice with chronic hyperuricemic nephropathy. Knockout of AMPK α2 reduced renal urate crystal deposition, probably through increasing the expression of the uric acid transporter, multidrug resistance protein 4. In summary, AMPK α2 is involved in acute and chronic hyperuricemia-induced kidney injury and may be associated with increased urate crystal deposition in the kidney., (© 2022. The Author(s).)

Peroxiredoxin 5 (PRDX5) is the member of Prxs family, widely reported to be involved in various types of cell death. We previously found that PRDX5 knockdown increases the susceptibility of cell death upon oxidative stress treatment. Ethyl β-carboline-3-carboxylate (β-CCE), an alkaloid extracted from Picrasma quassioides , has been reported to play a role in neuronal disease, but its anti-cancer potential on liver cancers remains unknown. Here, we studied the effect of PRDX5 on ethyl β-carboline-3-carboxylate (β-CCE)-induced apoptosis of hepatomas. High expression level of PRDX5 was deeply related with the postoperative survival of patients with liver cancer, indicating that PRDX5 may be a biomarker of live cancer processing. Moreover, PRDX5 over-expression in HepG2 cells significantly inhibited β-CCE-induced cell apoptosis and cellular ROS levels as well as mitochondrial dysfunction. Signalling pathway analysis showed that β-CCE could significantly up-regulate the ROS-dependent MAPK signalling, which were in turn boosts the mitochondria-dependent cell apoptosis. Moreover, PRDX5 over-expression could reverse the anti-cancer effects induced by β-CCE in HepG2 cells. Our findings suggest that PRDX5 has a protective role on β-CCE-induced liver cancer cell death and provides new insights for using its anti-cancer properties for liver cancer treatment., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)