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Xiaoqing Wei,1,* Junying Zhang,2,* Youwen Mei,3 Eqiong Li,4 Qianling Dai,1 Xiaoli Yang,1 Dan Luo,5 Biao Li,6 Ping Hua,7 Jian Cai,7 Hua Lai,8 Dongfeng Qi,9 Sha Lai,10 Mi Qin,11 Yonghong Lin4 1Department of Cervical Disease and Cervical Cancer Prevention and Treatment, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 2Clinical Laboratory Department, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 3Department of Reproduction and Infertility, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 4Department of Gynecology, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 5Department of Obstetrics, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 6Department of Neonatal Intensive Care Unit, Chengdu Women’ and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 7Department of Pathology, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 8Department of Radiation and Interventional Therapy, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 9Department of Ultrasonics, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 10Dermatology Department, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 11Department of Pediatric Surgery, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yonghong Lin; Xiaoqing Wei, Email linyhcd2011@163.com; xqcherry@163.comObjective: We report a case of Carmi Syndrome in a neonate.Aim: To share our lessons in diagnosis of the case of Carmi Syndrome.Case Report: Carmi Syndrome is an extremely rare autosomal recessive genetic disorder characterized the coexistence of pyloric atresia and junctional epidermolysis bullosa, and with aplasia cutis congenita in approximately 28% patients. In this case, a full-term male neonate was born to a G4P2+1L1 multipara through cesarean section delivery in hospital in a non-consanguineous marriage with 4000mL of II°meconium-stained amniotic fluid. He was found extensive skin loss over lower legs and other parts, with scattered blisters and bilateral microtia. Plain abdominal X-ray revealed a large gastric air bubble with no gas distally. The mother had an intrauterine fetal loss previously for reasons unknown. The dermatologist diagnosed the newborn with Bart Syndrome, while the pediatric surgeon diagnosed congenital pyloric atresia(CPA). The parents refused further treatment and the neonate passed away about 30 hours after birth.Outcome: The neonate passed away about 30 hours after birth.Conclusion: Lessons from this case:①.Rule out Carmi Syndrome in patients with PA, and differentiate Bart syndrome and Carmi Syndrome in patients with abnormal skin manifestations. ②. For rare and/or severe diseases, multidisciplinary teams(MDTs) should be establish. ③. Genetic counseling and prenatal diagnosis are necessary prior to subsequent childbearings. ④.Termination of pregnancy might be contemplated if certain indicators are revealed.Keywords: Carmi syndrome, bart syndrome, epidermolysis bullosa, EB, junctional epidermolysis bullosa, JEB, congenital pyloric atresia, CPA, aplasia cutis congenita, ACC, congenital localized absence of skin, CLAS, pyloric atresia, PA, epidermolysis bullosa with pyloric atresia, EB-PA, multidisciplinary teams, MDT

Li Guo,1,* Shi-Cui Hong,1,2,* Xuan Wang,1,3,* Sheng-Qi Wang,1,4 Neng Wang,4,5 Xiao-Qing Wei,1 Hong-Lin Situ,1,3,4 Zhi-Yu Wang1– 5 1Breast Disease Specialist Hospital of Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, 510120, People’s Republic of China; 2The Second Clinical College of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, 510120, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong Provincial Academy of Chinese Medical Sciences, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, 510120, People’s Republic of China; 4Guangdong-Hong Kong-Macau Joint Laboratory on Chinese Medicine and Immune Disease Research, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510120, People’s Republic of China; 5The Research Center for Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510120, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhi-Yu Wang, Breast Disease Specialist Hospital of Guangdong Provincial Hospital of Chinese Medicine, No. 55, Inner Road West, Higher Education Mega Center(Hospital Branch Address), Guangzhou, 510120, Guangdong, People’s Republic of China, Tel +86-18819480766, Email wangzhiyu@gzucm.edu.cnBackground: Triple-negative breast cancer (TNBC) is the most aggressive malignancy. Psychological distress and elevated CXCL1 level have been reported to be closely associated with the poor prognosis and quality of life of patients with TNBC. In preclinical studies using xenograft mouse models, XIAOPI formula, a nationally approved drug prescribed to patients at high risk for breast cancer, inhibited CXCL1 expression and improved survival. Traditional Chinese medicine has unique advantages in improving patients’ emotional disorders and quality of life. However, the impact of XIAOPI formula on the serum level of CXCL1, psychological distress, and quality of life among patients with TNBC is currently unknown.Methods: In this study, we designed a randomized, double-blind, placebo-controlled trial. Patients with TNBC were randomly assigned to receive either the XIAOPI formula or a placebo for three months. The primary outcomes include serum CXCL1 expression, Self-Rating Anxiety Scale (SAS), and the Self-Rating Depression Scale (SDS). Secondary outcomes included the Pittsburgh Sleep Quality Index (PSQI) and the Functional Assessment of Cancer Therapy-Breast (FACT-B).Results: A total of 60 patients with TNBC were enrolled in the investigation. The results showed that the XIAOPI formula significantly decreased CXCL1 expression compared with the control group. Moreover, in comparison to the placebo, the XIAOPI formula increased FACT-B scores while decreasing SDS, SAS, and PSQI scores.Conclusion: In patients with TNBC, XIAOPI formula may be effective in reducing CXCL1 levels, enhancing psychological well-being, and quality of life. While our research offers a natural alternative therapy that may enhance the prognosis of TNBC, future validation of its therapeutic effects will require large-scale, long-term clinical trials.Clinical Registration Number: Registration website: www.chictr.org.cn, Registration date: 2018-1-19, Registration number: ChiCTR1800014535.Keywords: anxiety, CXCL1, depression, quality of life, sleep quality, triple-negative breast cancer, XIAOPI formula

The article discusses a study on the insecticide tolerance ability of German cockroach, Blattella germanica towards propoxur and 2,2-dichlorovinyl dimethyl phosphate (dichlorvos). It is mentioned that nymphs from one week to six week of age was treated with propoxur and dichlorvos and demonstrate the tolerance ratio of 18.55 fold and 4.98 fold in four week and six week old nymph. It further demonstrates the decreasing activity of acetylcholinesterase with the increase in age.

Gambogic acid(GA), a caged xanthone derivative isolated from Garcinia Hanburyi, exhibits significant antitumor activity and has advanced to phase Ⅱ clinical trials for lung cancer treatment in China. However, the clinical application of GA is severely hindered by its inherent limitations, including poor water solubility, a lack of targeting specificity, and significant side effects. Novel drug delivery systems not only overcome these pharmacological deficiencies but also integrate multiple therapeutic modalities, transcending the limitations of monotherapeutic approaches. In this study, we designed a multifunctional nanodelivery platform(PDA-PEG-Fe(Ⅲ)-GOx-GA) using polydopamine(PDA) as the core material. After the modification of PDA with polyethylene glycol(PEG), Fe(Ⅲ) ions, glucose oxidase(GOx), and GA were sequentially loaded via coordination interactions, electrostatic adsorption, and hydrophobic interactions, respectively. This system demonstrated excellent physiological stability, hemocompatibility, and photothermal conversion efficiency. Notably, under dual stimuli of pH and near-infrared(NIR) irradiation, PDA-PEG-Fe(Ⅲ)-GOx-GA achieved controlled GA release, with a cumulative release rate of 58.3% at 12 h, 3.6-fold higher than that under non-stimulated conditions. Under NIR irradiation, the synergistic effects of PDA-mediated photothermal therapy, Fe(Ⅲ)-induced chemodynamic therapy, GOx-generated starvation therapy, and GA-mediated chemotherapy resulted in effective inhibition of tumor cell proliferation(91.5% inhibition rate) and induction of apoptosis(83.3% apoptosis rate). This multi-modal approach realized a comprehensive treatment strategy for lung cancer, integrating various therapeutic pathways.

Background and Aim: Angelica sinensis (Oliv.) Diels (Danggui, DG), exhibits potential in myocardial infarction (MI) treatment. However, research on its synergistic combinations for cardioprotective effects has been limited owing to inadequate approaches., Experimental Procedure: We identified certain phenolic acids and phthalein compounds in DG. Network pharmacology analysis and experimental validation revealed the components that protected H9c2 cells and reduced lactate dehydrogenase levels. Subsequently, a combination of computational experimental strategies and a secondary phenotypic optimization platform was employed to identify effective component combinations with synergistic interactions. The Chou-Talalay and Zero Interaction Potency (ZIP) models were utilized to quantify the synergistic relationships. The optimal combination identified, Z -Ligustide and Chlorogenic acid (Z-LIG/CGA), was evaluated for its protective effects on cardiac function and cardiomyocytes apoptosis induced by inflammatory in a mouse model of induced by left anterior descending coronary artery ligation. Flow cytometry was further utilized to detect the polarization ratio of M1/M2 macrophages and the expression of inflammatory cytokines in serum was measured, assessing the inhibition of inflammatory responses and pro-inflammatory signaling factors by Z-LIG/CGA., Key Results: Quadratic surface analysis revealed that the Z-LIG/CGA combination displayed synergistic cardioprotective effects (combination index value <1; ZIP value >10). In vivo , Z-LIG/CGA significantly improved cardiac function and reduced the fibrotic area in mice post-MI, surpassing the results in groups treated with Z-LIG or CGA alone. Compared to the MI group, the Z-LIG/CGA group exhibited decreased ratios of the myocardial cell apoptosis-related proteins BAX/Bcl-2 and Cleaved Caspase-3/Caspase-3 in mice. Further research revealed that Z-LIG/CGA treatment significantly increased IL-1R2 levels, significantly decreased IL-17RA levels, and inhibited the activation of p-STAT1, thereby alleviating cell apoptosis after MI. Additionally, the Z-LIG/CGA combination significantly inhibited the ratio of M1/M2 macrophages and suppressed the expression levels of pro-inflammatory cytokines IL-1β, IL-6, IL-17, and TNF-α in the serum., Conclusion and Implications: We successfully identified a synergistic drug combination, Z-LIG/CGA, which improves MI outcomes by inhibiting cardiomyocyte apoptosis and inflammatory damage through modulating macrophage polarization and regulating the IL-1R2/IL-17RA/STAT1 signaling pathway. This study provides a charming paradigm to explore effective drug combinations in traditional Chinese medicine and a promising treatment for MI., 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 Wang, Fan, Wei, Chai, Li, Gao, Liu and Guo.)

Background and Aims: This study aimed to explore potential hub genes and pathways of plaque vulnerability and to investigate possible therapeutic targets for acute coronary syndrome (ACS)., Methods and Results: Four microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs), weighted gene coexpression networks (WGCNA) and immune cell infiltration analysis (IIA) were used to identify the genes for plaque vulnerability. Then, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, Disease Ontology, Gene Ontology annotation and protein-protein interaction (PPI) network analyses were performed to explore the hub genes. Random forest and artificial neural networks were constructed for validation. Furthermore, the CMap and Herb databases were employed to explore possible therapeutic targets. A total of 168 DEGs with an adjusted P < 0.05 and approximately 1974 IIA genes were identified in GSE62646. Three modules were detected and associated with CAD-Class, including 891 genes that can be found in GSE90074. After removing duplicates, 114 hub genes were used for functional analysis. GO functions identified 157 items, and 6 pathways were enriched for the KEGG pathway at adjusted P < 0.05 (false discovery rate, FDR set at < 0.05). Random forest and artificial neural network models were built based on the GSE48060 and GSE34822 datasets, respectively, to validate the previous hub genes. Five genes (GZMA, GZMB, KLRB1, KLRD1 and TRPM6) were selected, and only two of them (GZMA and GZMB) were screened as therapeutic targets in the CMap and Herb databases., Conclusion: We performed a comprehensive analysis and validated GZMA and GZMB as a target for plaque vulnerability, which provides a therapeutic strategy for the prevention of ACS. However, whether it can be used as a predictor in blood samples requires further experimental verification., Competing Interests: Declaration of competing interest The authors have no potential conflicts of interest to report., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The midpoint transverse process to pleura (MTP) block, a novel technique for thoracic paravertebral block (TPVB), was first employed in laparoscopic renal cyst decortication., Case Summary: Thoracic paravertebral nerve block is frequently employed for perioperative analgesia during laparoscopic cyst decortication. To address safety concerns associated with TPVBs, we administered MTP blocks in two patients prior to administering general anesthesia for laparoscopic cyst decortication. The MTP block was performed at the T9 level under ultrasound guidance, with 20 mL of 0.5% ropivacaine injected. Reduced sensation to cold and pinprick was observed from the T8 to T11 dermatome levels. Immediately postoperative Numeric Pain Rating Scale scores were 0/10 at rest and on movement, with none exceeding a mean 24 h numeric rating scale > 3., Conclusion: MTP block was effective technique for providing postoperative analgesia for patients undergoing laparoscopic renal cyst decortication., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To describe the prevalence of food allergy among children aged 0-5 years in China and to explore related influencing factors. Methods: Multistage stratified random sampling method was used to collect data from 275 surveillance sites of the China National Nutrition and Health Survey of Chinese children and lactating mothers programs in 31 provinces (autonomous regions and municipalities) of China in 2016-2017. A total of 70 107 participants aged 0-5 years were included in this study. The study collected information of participants' demographic characteristics and food allergies by face-to-face questionnaire. The prevalence of food allergy was analyzed, using the complex data weighting method. The logistic regression models were used to analyze the influencing factors related to food allergy. Results: The overall prevalence of self-reported food allergy among children aged 0-5 years was 4.81%. Prevalence rates in infants aged 0-5 months, and 6-23 months and preschool children aged 2-5 years were 0.81%, 4.68% and 5.26%, respectively. The results of logistic analysis showed that there was a significantly positive correlation between factors including children from 6 months to 5 years old, urban area, southwest area, first-born, mothers with college education or above, and the prevalence of food allergy in children. Shrimp, poultry eggs, crab shellfish, fruit, milk and fish appeared the common allergic foods in children aged 0-5 years, with prevalence rates of self-reported food allergy as 1.55%, 1.25%, 0.99%, 0.97%, 0.87% and 0.86%, respectively. The proportion of single food allergy in children with allergies was 69.85%. Conclusions: Among children aged 0-5 years, the prevalence of self-reported food allergy increases with age, in China. Foods that is prone to allergies include fish, shrimp, crab, shellfish, poultry eggs, milk and fruits, etc . Most allergies were only caused by single food in children, under observation.

Pacific Biosciences (PacBio) HiFi sequencing technology generates long reads (>10 kbp) with very high accuracy (<0.01% sequencing error). Although several de novo assembly tools are available for HiFi reads, there are no comprehensive studies on the evaluation of these assemblers. We evaluated the performance of 11 de novo HiFi assemblers on (1) real data for three eukaryotic genomes; (2) 34 synthetic data sets with different ploidy, sequencing coverage levels, heterozygosity rates, and sequencing error rates; (3) one real metagenomic data set; and (4) five synthetic metagenomic data sets with different composition abundance and heterozygosity rates. The 11 assemblers were evaluated using quality assessment tool (QUAST) and benchmarking universal single-copy ortholog (BUSCO). We also used several additional criteria, namely, completion rate, single-copy completion rate, duplicated completion rate, average proportion of largest category, average distance difference, quality value, run-time, and memory utilization. Results show that hifiasm and hifiasm-meta should be the first choice for assembling eukaryotic genomes and metagenomes with HiFi data. We performed a comprehensive benchmarking study of commonly used assemblers on complex eukaryotic genomes and metagenomes. Our study will help the research community to choose the most appropriate assembler for their data and identify possible improvements in assembly algorithms., (© 2024 Yu et al.; Published by Cold Spring Harbor Laboratory Press.)

Objective: To investigate the ultrasonographic features of medullary thyroid carcinomas (MTCs) of different sizes and supply valid information for separating MTCs from papillary thyroid carcinomas (PTCs). Methods: There were 87 patients with MTC and 220 patients with PTC detected by ultrasonography and confirmed by pathology at Tianjin Medical University Cancer Institute and Hospital from June 2018 to March 2022. Nodules were divided into the large nodule group (the maximum diameter of the tumor was＞1 cm) and the small nodule group (the maximum diameter of the tumor was ≤1 cm). There were 97 cases in the small nodule group, including 28 cases of MTC and 69 cases of PTC. There were 210 cases in the large nodule group, including 59 cases of MTC and 151 cases of PTC. After stratification by thyroid nodules, ultrasonographic features of thyroid nodules and metastatic lymph nodes, preoperative serum calcitonin (CT) and carcinoembryonic antigen (CEA) levels were compared between MTC and PTC patients. Results: In the small nodule group, the proportion of MTCs exhibiting hypoecho, smooth margins, and having blood flow signals was higher than that of PTCs, with statistically significant differences (all P ＜0.05). In the large nodule group, the proportion of MTCs showing cystic solidity, hypoecho, smooth margins, blood flow, and the type Ⅳvascular distribution was higher than PTCs, and the difference of calcification type between them was also statistically significant (all P ＜0.05). In contrast, the differences in the number of lesions and aspect ratio between MTCs and PTCs were not statistically significant regardless of nodule size (all P ＞0.05). In the small nodule group,6 metastatic lymph nodes of medullary thyroid carcinoma (LNM-MTC) and 11 metastatic lymph nodes of papillary thyroid carcinoma (LNM-PTC) were correctly diagnosed by ultrasound, respectively. The diagnostic compliance rate of ultrasound was 78.6% (22/28) and 78.3% (54/69), respectively, with no statistically significant difference ( P =0.973). In the large nodule group, 28 LNM-MTC and 11 LNM-PTC were correctly diagnosed by ultrasound, respectively. The diagnostic compliance of ultrasound was 88.1% (52/59) and 73.5% (111/151), respectively, which was statistically significant ( P =0.022). Among them, 82.1% of LNM-MTC and 56.6% of LNM-PTC showed abnormal blood flow signals, with a statistically significant difference ( P =0.016). There were significant differences in preoperative serum CT and CEA levels of different sizes of MTCs (all P ＜0.05). Conclusions: Different sizes of MTCs require diverse demonstrative criteria. Abnormal blood flow signal is of great significance in the diagnosis of LNM-MTC. Within the absence of ultrasonic characteristics, preoperative serum CT test can provide confidence for the diagnosis of MTC.

Objective: To investigate the correlations between thyroid function, renal function, and depression., Methods: Clinical data of 67 patients with Major depressive disorder (MDD) and 36 healthy control subjects between 2018 and 2021 were collected to compare thyroid and renal function. Thyroid and renal functions of depressed patients were then correlated with the Hamilton Depression Rating Scale (HAMD) and the Hamilton Anxiety Rating Scale (HAMA).Spearman correlation analysis was used to find the correlation between renal function, thyroid function, and depression. A logistic regression was performed to find significant predictors of depression., Results: Triiodothyronine protamine (T3), thyroxine (T4), free triiodothyronine protamine (FT3), uric acid, sodium, and anion gap were lower in the MDD group than in the control group ( p  < 0.05). Correlation analysis of thyroid function, renal function, and factor terms of HAMD in the MDD group suggested that diurnal variation, hopelessness, and depression level were positively correlated with thyrotropin (TSH) ( p  < 0.05). Cognitive disturbance, retardation, and depression level were negatively correlated with creatinine ( p  < 0.05). Diurnal variation was negatively correlated with sodium ion ( p  < 0.01); hopelessness and depression level were positively correlated with chloride ion ( p  < 0.05); diurnal variation, retardation, and depression level were negatively correlated with anion gap ( p  < 0.05). Diurnal variation ( p  < 0.01) and retardation ( p  < 0.05) were negatively correlated with osmolality. Cognitive disturbance and depression level were positively correlated with estimated glomerular filtration rate (eGFR) ( p  < 0.05). In the MDD group, correlation analysis of thyroid function, renal function, and HAMA factor terms suggested that the total HAMA score and anxiety level were positively correlated with chloride ion ( p  < 0.05); psychic anxiety, total HAMA score, and anxiety level were negatively correlated with anion gap ( p  < 0.05). Furthermore, a low level of anion gap was an independent risk factor for depression and anxiety levels ( p  < 0.05)., Conclusion: Low thyroid function and reduced waste metabolized by the kidneys in patients with MDD suggest a low intake and low metabolism in depressed patients. In addition, subtle fluctuations in the anion gap in depressed patients were strongly correlated with the degree of depression and anxiety., 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 Liang, Wang, Wei, Su and Zhang.)

Jiming Powder is a traditional ancient prescription with good therapeutic effect in the treatment of heart failure, but its mechanism lacks further exploration. In this study, a mouse model of coronary artery ligation was used to evaluate the effect and mechanism of Jiming Powder on myocardial fibrosis in mice with myocardial infarction. The study constructed a mouse model of heart failure after myocardial infarction using the method of left anterior descending coronary artery ligation. The efficacy of Jiming Powder was evaluated from multiple angles, including ultrasound imaging, hematoxylin-eosin(HE) staining, Masson staining, Sirius Red staining, and serum myocardial enzyme spectrum detection. Western blot analysis was performed to detect key proteins involved in ventricular remodeling, including transforming growth factor-β1(TGF-β1), α-smooth muscle actin(α-SMA), wingless-type MMTV integration site family member 3a(Wnt3a), β-catenin, matrix metallopeptidase 2(MMP2), matrix metallopeptidase 3(MMP3), TIMP metallopeptidase inhibitor 1(TIMP1), and TIMP metallopeptidase inhibitor 2(TIMP2). The results showed that compared with the model group, the high and low-dose Jiming Powder significantly reduced the left ventricular internal diameter in systole(LVID;s) and diastole(LVID;d), increased the left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), effectively improved cardiac function in mice after myocardial infarction, and effectively reduced the levels of myocardial injury markers such as creatine kinase(CK), creatine kinase isoenzyme(CK-MB), and lactic dehydrogenase(LDH), thus protecting ischemic myocardium. HE staining showed that Jiming Powder could attenuate myocardial inflammatory cell infiltration after myocardial infarction. Masson and Sirius Red staining demonstrated that Jiming Powder effectively inhibited myocardial fibrosis, reduced the collagen Ⅰ/Ⅲ ratio in myocardial tissues, and improved collagen remodeling after myocardial infarction. Western blot results showed that Jiming Powder reduced the expression of TGF-β1, α-SMA, Wnt3a, and β-catenin, decreased the levels of MMP2, MMP3, and TIMP2, and increased the level of TIMP1, suggesting its role in inhibiting cardiac fibroblast transformation, reducing extracellular matrix metabolism in myocardial cells, and lowering collagen Ⅰ and α-SMA content, thus exerting an anti-myocardial fibrosis effect after myocardial infarction. This study revealed the role of Jiming Powder in improving ventricular remodeling and treating myocardial infarction, laying the foundation for further research on the pharmacological effect of Jiming Powder.

In this study, untargeted metabolomics was conducted using the liquid chromatography-tandem mass spectrometry(LC-MS/MS) technique to analyze the potential biomarkers in the plasma of mice with heart failure with preserved ejection fraction(HFpEF) induced by a high-fat diet(HFD) and nitric oxide synthase inhibitor(Nω-nitro-L-arginine methyl ester hydrochloride, L-NAME) and explore the pharmacological effects and mechanism of Jiming Powder in improving HFpEF. Male C57BL/6N mice aged eight weeks were randomly assigned to a control group, a model group, an empagliflozin(10 mg·kg~(-1)·d~(-1)) group, and high-and low-dose Jiming Powder(14.3 and 7.15 g·kg~(-1)·d~(-1)) groups. Mice in the control group were fed on a low-fat diet, and mice in the model group and groups with drug intervention were fed on a high-fat diet. All mice had free access to water, with water in the model group and Jiming Powder groups being supplemented with L-NAME(0.5 g·L~(-1)). Drugs were administered on the first day of modeling, and 15 weeks later, blood pressure and cardiac function of the mice in each group were measured. Heart tissues were collected for hematoxylin-eosin(HE) staining to observe pathological changes and Masson's staining to observe myocardial collagen deposition. Untargeted metabolomics analysis was performed on the plasma collected from mice in each group, and metabolic pathway analysis was conducted using MetaboAnalyst 5.0. The results showed that the blood pressure was significantly lower and the myocardial concentric hypertrophy and left ventricular diastolic dysfunction were significantly improved in both the high-dose and low-dose Jiming Powder groups as compared with those in the model group. HE and Masson staining showed that both high-dose and low-dose Jiming Powder significantly alleviated myocardial fibrosis. In the metabolomics experiment, 23 potential biomarkers were identified and eight strongly correlated metabolic pathways were enriched, including linoleic acid metabolism, histidine metabolism, alpha-linolenic acid metabolism, glycerophospholipid metabolism, purine metabolism, porphyrin and chlorophyll metabolism, arachidonic acid metabolism, and pyrimidine metabolism. The study confirmed the pharmacological effects of Jiming Powder in lowering blood pressure and ameliorating HFpEF and revealed the mechanism of Jiming Powder using the metabolomics technique, providing experimental evidence for the clinical application of Jiming Powder in treating HFpEF and a new perspective for advancing and developing TCM therapy for HFpEF.

Background: Percutaneous transluminal coronary angioplasty, while an effective intervention, can frequently lead to acute occlusion with severe consequences. Although clinical trials have demonstrated the efficacy of drug-coated balloons (DCB) in treating acute coronary artery occlusion and in preventing restenosis, there has been limited exploration on the use of DCB in treating de novo lesions in large vessels. Currently, DCB are only recommended for patients with small vessel lesions and in-stent restenosis lesions, those at high risk of bleeding, and other special groups of patients., Case Summary: This report presents a case of successful drug-coated balloon treatment of de novo lesions in large coronary vessels. Postoperatively, the patient demonstrated favorable recovery, with subsequent examination results revealing no significant differences from the previous examination., Conclusion: The successful treatment of the patient in our case highlights the potential of DCB in the treatment of de novo lesions in large coronary vessels., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

In the process of orthodontic tooth movement (OTM), periodontal ligament fibroblasts (PDLFs) must undergo osteogenic differentiation. OTM increased the expression of Zinc finger and BTB domain-containing 16 (ZBTB16), which is implicated in osteogenic differentiation. Our goal was to investigate the mechanism of PDLF osteogenic differentiation mediated by ZBTB16. The OTM rat model was established, and PDLFs were isolated and exposed to mechanical force. Hematoxylin-eosin staining, Alizarin Red staining, immunofluorescence, and immunohistochemistry were carried out. The alkaline phosphatase (ALP) activity was measured. Dual-luciferase reporter gene assay and chromatin immunoprecipitation assay were conducted. In OTM models, ZBTB16 was significantly expressed. Additionally, there was an uneven distribution of PDLFs in the OTM group, as well as an increase in fibroblasts and inflammatory infiltration. ZBTB16 interference hindered PDLF osteogenic differentiation and decreased Wnt and β-catenin levels. Meanwhile, ZBTB16 activated the Wnt/β-catenin pathway. ZBTB16 also enhanced the expression of the osteogenic molecules osterix, osteocalcin (OCN), osteopontin (OPN), and bone sialo protein (BSP) at mRNA and protein levels. The interactions between Wnt1 and ZBTB16, as well as GCN5 and ZBTB16, were also verified. The adeno-associated virus-shZBTB16 injection also proved to inhibit osteogenic differentiation and reduce tooth movement distance in in vivo tests. ZBTB16 was up-regulated in OTM. Through acetylation modification of ZBTB16, GCN5 regulated the Wnt/β-catenin signaling pathway and further mediated PDLF osteogenic differentiation., Competing Interests: The authors declare there are no competing interests.

Three new cyanide-bridged compounds {[Mn(( S , S )-Dpen)] 3 [Mn(( S , S )-Dpen)(H 2 O)][Mo(CN) 7 ] 2 ·4H 2 O·4C 2 H 3 N} n (1-SS), {[Mn(( R , R )-Dpen)] 3 [Mn(( R , R )-Dpen)(H 2 O)][Mo(CN) 7 ] 2 ·4.5H 2 O·4C 2 H 3 N} n (1-RR), and {[Mn(Chxn)][Mn(Chxn)(H 2 O) 0.8 ][Mo(CN) 7 ]·H 2 O·4C 2 H 3 N} n (2) ( SS / RR -Dpen = ( S , S )/( R , R )-1,2-diphenylethylenediamine and Chxn = 1,2-cyclohexanediamine) have been successfully synthesized from the self-assembly reaction of the [Mo III (CN) 7 ] 4- unit, the Mn II ions, and two chiral bidentate chelating ligands. Single-crystal structure determinations show that compounds 1-SS and 1-RR containing ligands SS / RR -Dpen are enantiomers and crystallize in the chiral space group P 2 1 . On the other hand, compound 2 crystallizes in the achiral centrosymmetric space group P 1̄ due to the racemization of the SS / RR -Chxn ligands during the growth of the crystals. Despite their different space groups and ligands, all three compounds exhibit similar framework structures consisting of cyano-bridged Mn II -Mo III two-dimensional layers separated by the bidentate ligands. The circular dichroism (CD) spectra have further demonstrated the enantiopure character of compounds 1-SS and 1-RR. Magnetic measurements revealed that all three compounds display ferrimagnetic ordering with similar critical temperatures of about 40 K. The chiral enantiomers 1-SS and 1-RR exhibit the magnetic hysteresis loop with a coercive field of about 8000 Oe at 2 K, which is by far the highest for all known Mn II -[Mo III (CN) 7 ] 4- magnets. Analyses of their structures and magnetic properties indicated that their magnetic properties depend on the anisotropic magnetic interactions between the Mn II and Mo III centers, which are closely related to the C-N-M bond angles.

As the disease with high morbidity and mortality in the world, heart failure affects the development of human society. Due to its complicated pathology and limited treatment options, it is urgent to discover new disease targets and develop new treatment strategies. As innate immune cells accompanied by the evolution of heart failure, macrophages play an important role in cardiac homeostasis and stress. In recent years, the role of macrophages in the heart has attracted more and more attention as a potential target for heart failure intervention, and the research on cardiac macrophages has made important progress. Traditional Chinese medicine(TCM) has significant effects on regulating inflammatory response, treating heart failure, and maintaining homeostasis. In this article, researches on the functions of cardiac macrophages and application of TCM were reviewed from the source and classification of cardiac macrophages and the relationship of macrophages and cardiac inflammation, myocardial fibrosis, cardiac angiogenesis, and cardiac electrical conduction, which provided a basis for further basic research and clinical applications.

Experimental models that consider host-pathogen interactions are relevant for improving knowledge about oral candidiasis. The aim of this study was to assess the epithelial immune responses, Candida penetration of cell monolayers, and virulence during mixed species culture infections. Single species cultures of Candida albicans and mixed cultures (C. albicans, Streptococcus mutans, and Streptococcus sanguinis) were used to infect monolayers of HaCaT and FaDu ATCC HTB-43 cells for 12 h. After infection, IL-18 and IL-34 gene expression was measured to assess epithelial cell immune responses, and lactate dehydrogenase (LDH) activity was measured as an indicator of cell damage. Microscopy determined C. albicans morphology and penetration of fungal cells through the keratinocyte monolayer. Monolayers devoid of infection served as controls. Data were analyzed by an ANOVA one-way test followed by Tukey's post-hoc test (α = 0.05). The results found that IL-18 and IL-34 gene expression and LDH activity were significantly (p < 0.05) upregulated for both cell lines exposed to mixed species cultures compared with C. albicans alone. Candida albicans yeast and hyphae were evident in C. albicans only infections. In contrast, monolayers infected by C. albicans, S. mutans, and S. sanguinis exhibited higher microbial invasion with several hyphal aggregates detected. The presence of streptococci in C. albicans infection enhances the virulence and pathogenicity of the fungus with associated increased immune responses and tissue damage. Extrapolation of these findings to oral infection would indicate the added potential benefit of managing bacterial components of biofilms during treatment.

Interleukin 37 (IL-37), a member of the IL-1 family, is considered a suppressor of innate and adaptive immunity and, hence is a regulator of tumor immunity. However, the specific molecular mechanism and role of IL-37 in skin cancer remain unclear. Here, we report that IL-37b-transgenic mice (IL-37tg) treated with the carcinogenic 7,12-dimethylbenzoanthracene (DMBA)/12-o-tetradecylphorbol-13-acetate (TPA) exhibited enhanced skin cancer and increased tumor burden in the skin by inhibiting the function of CD103 + dendritic cells (DCs). Notably, IL-37 induced rapid phosphorylation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), and via single immunoglobulin IL-1-related receptor (SIGIRR), inhibited the long-term Akt activation. Specifically, by affecting the SIGIRR-AMPK-Akt signaling axis, which is related to the regulation of glycolysis in CD103 + DCs, IL-37 inhibited their anti-tumor function. Our results show that a marked correlation between the CD103 + DC signature (IRF8, FMS-like tyrosine kinase 3 ligand, CLEC9A, CLNK, XCR1, BATF3, and ZBTB46) and chemokines C-X-C motif chemokine ligand 9, CXCL10, and CD8A in a mouse model with DMBA/TPA-induced skin cancer. In a word, our results highlight that IL-37 as an inhibitor of tumor immune surveillance through modulating CD103 + DCs and establishing an important link between metabolism and immunity as a therapeutic target for skin cancer., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.)

Background: Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death worldwide. Angiogenic factors may be valuable indices of tumor recurrence and treatment and potentially useful markers for predicting the response to antiangiogenesis therapy. Vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) are major drivers of tumor angiogenesis. Preoperatively predicting the expression of VEGF and MMPs is crucial for treating HCC. Intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) has been successfully used in the differential diagnosis of HCC, pathological grading, and treatment response evaluation. However, the correlations between IVIM-DWI parameters and VEGF and MMP expression have not been reported. This study provides a preliminary analysis of the correlation between IVIM-DWI parameters and the expression of VEGF, MMP-2, and MMP-9 to investigate the value of IVIM-DWI in the noninvasive evaluation of angiogenesis in HCC., Methods: IVIM-DWI was performed in 61 patients with HCC 1 week before they underwent surgical resection. VEGF, MMP-2, and MMP-9 expression was detected using immunohistochemistry staining. Spearman correlation analysis was used to analyze the correlations between the IVIM-DWI parameters and VEGF, MMP-2, and MMP-9 expression in HCC., Results: The fast apparent diffusion coefficient fraction ( f ) value was positively correlated with the expression of VEGF (P<0.001), MMP-2 (P=0.002), and MMP-9 (P<0.001). The fast apparent diffusion coefficient ( D *) was positively correlated with VEGF (P<0.001) and MMP-9 (P<0.001) expression but was not correlated with MMP-2 (P=0.659) expression. The apparent diffusion coefficient (ADC) and slow apparent diffusion coefficient ( D ) values were not significantly correlated with the expression of VEGF (P=0.103 and P=0.543, respectively), MMP-2 (P=0.596 and P=0.338, respectively), or MMP-9 (P=0.102 and P=0.660, respectively)., Conclusions: IVIM-DWI can be used to noninvasively evaluate angiogenesis in HCC., 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-22-271/coif). The authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Objective: To investigate the effect of adipocytes in the bone marrow microenvironment of patients with multiple myeloma (MM) on the pathogenesis of MM., Methods: Bone marrow adipocytes (BMA) in bone marrow smears of health donors (HD) and newly diagnosed MM (ND-MM) patients were evaluated with oil red O staining. The mesenchymal stem cells (MSC) from HD and ND-MM patients were isolated, and in vitro co-culture assay was used to explore the effects of MM cells on the adipogenic differentiation of MSC and the role of BMA in the survival and drug resistance of MM cells. The expression of adipogenic/osteogenic differentiation-related genes PPAR-γ , DLK1 , DGAT1 , FABP4 , FASN and ALP both in MSC and MSC-derived adipocytes was determined with real-time quantitative PCR. The Western blot was employed to detect the expression levels of IL-6, IL-10, SDF-1α, TNF-α and IGF-1 in the supernatant with or without PPAR-γ inhibitor., Results: The results of oil red O staining of bone marrow smears showed that BMA increased significantly in patients of ND-MM compared with the normal control group, and the BMA content was related to the disease status. The content of BMA decreased in the patients with effective chemotherapy. MM cells up-regulated the expression of MSC adipogenic differentiation-related genes PPAR-γ , DLK1 , DGAT1 , FABP4 and FASN , but the expression of osteogenic differentiation-related gene ALP was significantly down-regulated. This means that the direct consequence of the interaction between MM cells and MSC in the bone marrow microenvironment is to promote the differentiation of MSC into adipocytes at the expense of osteoblasts, and the cytokines detected in supernatant changed. PPAR-γ inhibitor G3335 could partially reverse the release of cytokines by BMA. Those results confirmed that BMA regulated the release of cytokines via PPAR-γ signal, and PPAR-γ inhibitor G3335 could distort PPAR-γ mediated BMA maturation and cytokines release. The increased BMA and related cytokines effectively promoted the proliferation, migration and drug resistance of MM cells., Conclusion: The BMA and its associated cytokines are the promoting factors in the survival, proliferation and migration of MM cells. BMA can protect MM cells from drug-induced apoptosis and plays an important role in MM treatment failure and disease progression.

A two-dimensional (2D) cobalt(II) metal-organic framework (MOF) constructed by a ditopic organic ligand, formulated as {[Co(Hbic)(H 2 O)]·4H 2 O} n (1) (H 2 bic = 1 H -benzimidazole-5-carboxylic acid), was hydrothermally synthesized and structurally characterized. Single-crystal X-ray diffraction shows that the distorted octahedral Co 2+ ions, as coordination nodes, are bridged to form 2D honeycomb networks, which are further organized into a 3D supramolecular porous framework through multiple hydrogen bonds and interlayer π-π interactions. Dynamic crystallography experiments reveal the anisotropic thermal expansion behavior of the lattice, suggesting a flexible hydrogen-bonded 3D framework. Interestingly, hydrogen-bonded (H 2 O) 4 tetramers were found to be located in porous channels, yielding 1D proton transport pathways. As a result, the compound exhibited a high room-temperature proton conductivity of 1.6 × 10 -4 S cm -1 under a relative humidity of 95% through a Grotthuss mechanism. Magnetic investigations combined with theoretical calculations reveal giant easy-plane magnetic anisotropy of the distorted octahedral Co 2+ ions with the experimental and computed D values being 87.1 and 109.3 cm -1 , respectively. In addition, the compound exhibits field-induced slow magnetic relaxation behavior at low temperatures with an effective energy barrier of U eff = 45.2 cm -1 . Thus, the observed electrical and magnetic properties indicate a rare proton conducting SIM-MOF. The foregoing results provide a unique bifunctional cobalt(II) framework material and suggest a promising way to achieve magnetic and electrical properties using a supramolecular framework platform.

Spin crossover (SCO) complexes have been extensively explored as bistable materials and recently used as molecular modules for the development of new multifunctional molecular magnetic materials. Herein, we present the synthesis, crystal structure, magnetic, and electrical properties of a mononuclear cobalt complex constructed by a halogen-functionalized terpyridine derivative and organosulfonate. A complete and gradual spin transition with the T 1/2 =200 K was observed for the Co 2+ ions through both the magnetic measurement and dynamic crystallographic experiments. Interestingly, considerable room temperature proton conductivity of 6.9×10 -5  S cm -1 under 98% relative humidity was evidenced because of the presence of sulfonate-assisted hydrogen-bonded proton hopping pathways. The forgoing results not only provide an unprecedented proton-conducting cobalt(II) SCO complex but also a promising way for the design and construction of bifunctional SCO molecular conductors via the incorporation of SCO transition and proton conduction., (© 2022 Wiley-VCH GmbH.)

The supramolecular assembly of hexaaquacobalt(II) nitrate and a tetradentate carboxylate ligand resulted in the isolation of a cobalt hydrogen-bonded organic framework (HOF). Variable-temperature X-ray diffraction experiments reveal high thermal stability of the framework sustained by charge-assisted, multiple hydrogen bonding interactions with the co-former. Interestingly, the material shows field-induced slow relaxation of magnetization originating from the magnetically anisotropic Co 2+ ions within the supramolecular framework, revealing a rare single-ion magnet (SIM) HOF. Additionally, the HOF also exhibits high proton conductivity above 100 °C due to the extensive H-bond networks and high content of water and carboxylate within the material. More importantly, these results not only observe the magnetic and electrical properties of an old molecule but also demonstrate a significant turn-on effect of multifunctionalities from non-functional synthons achieved in a supramolecular approach.

A molecular dysprosium(III) complex [Dy(DClQ) 3 (H 2 O) 2 ] (1) was used as a building unit for the construction of lanthanide SMMs, leading to the isolation of two dinuclear Dy(III) complexes, namely [Dy 2 (DClQ) 6 (MeOH) 2 ] (2) and [Dy 2 (DClQ) 6 (bpmo) 2 ]·6MeCN (3) ( DClQ = 5,7-dichloro-8-hydroxyquinoline, bpmo = 4,4'-dipyridine-oxide). Structural analyses revealed the same N 3 O 5 coordination environment of the Dy(III) centers with a distorted biaugmented trigonal prism ( C 2V symmetry) and triangular dodecahedron ( D 2d symmetry) for 2 and 3, respectively. Magnetic studies revealed the presence of ferromagnetic and weak antiferromagnetic exchange interactions between the Dy 3+ centers in 2 and 3, respectively. Interestingly, slow relaxation of magnetization at zero fields was evidenced with an U eff of 51.4 K and 159.0 K for complexes 2 and 3, respectively. The detailed analysis of relaxation dynamics discloses that the Orbach process is dominant for 2 whereas Raman and QTM play an important role in 3. Theoretical calculations were carried out to provide insight into the magnetic exchange interactions and relaxation dynamics for the complexes. Due to a single-ion magnet (SIM) of 1, the foregoing results demonstrate a SIM modular synthetic route for the preparation of dinuclear lanthanide SMMs.

In this work, a specific monoclonal antibody against tyramine was produced based on a new hapten design. Then, we developed a high-resolution multicolor colorimetric immunoassay for tyramine based on this antibody by integrating enzyme-induced multicolor generation with smartphone-assistant signal readout. The multicolor generation is due to the shift of the local surface plasmon resonance band of gold nanostructure controlled by alkaline phosphatase-induced the growth of gold nanostars. Quantitative detection of tyramine was achieved via analyzing the red/blue channel values of assay solution's image taken by a smartphone with the support of a color recognizer application. The limit of detection of this immunoassay for tyramine detection in beef, pork and yoghurt was 19.7 mg/kg or L. The average recoveries were between 83 % and 103 %., and the results were validated by high performance liquid chromatography to be reliable. Overall, this developed immunoassay provides a promising platform for on-site detection of tyramine., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Traditional Chinese medicine (TCM) prescriptions have multiple bioactive properties. "Gui Zhi-Shao Yao" herb pair is widely used to treat chronic pain (CP), as well as anxiety and depression. However, its related targets and underlying mechanisms have not been deciphered., Methods: In this study, the network pharmacology method was used to explore the bioactive components and targets of "Gui Zhi-Shao Yao" herb pair and further elucidate its potential biological mechanisms of action in the treatment of CP with comorbid anxiety disorder (AD) and mental depression (MD)., Results: Following a series of analyses, we identified 15 active compounds, hitting 130 potential targets. After the intersections the targets of this herb pair and CP, AD and MD - sorted by the value of degree - nine targets were identified as the vital ones: Akt1, IL6, TNF, PTGS2, JUN, CASP3, MAPK8, PPARγ and NOS3. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis results demonstrated 11 pathways, such as AGE-RAGE signalling pathway, IL-17 signalling pathway, TNF signalling pathway, which primarily participate in the pathological processes., Conclusions: This study preliminarily predicted and verified the pharmacological and molecular mechanisms of "Gui Zhi-Shao Yao" herb pair for treating CP with comorbid AD and MD from a holistic perspective. In vivo and in vitro experiments will be required to further investigate the mechanisms.KEY MESSAGEA network pharmacology approach was applied to identify key targets and molecular mechanisms.Nine targets were regarded as the vital targets for chronic pain with comorbid anxiety and depression.Predicted 11 pathways were the potential therapy targets and pharmacological mechanism of "Gui Zhi-Shao Yao" herb pair.

Cardiovascular diseases seriously affect human health and their prevalence continues to increase with the aging of the population. The integrated therapy of traditional Chinese medicine(TCM) and western medicine for cardiovascular diseases has achieved certain results, but it is still faced with new challenges. Studies have shown that inflammation plays an important role in the development of cardiovascular diseases and some of these mechanisms have common features. For example, in cardiovascular diseases, C-C motif chemokine receptor 2(CCR2)-expressing macrophages increase and promote inflammation, and excessive activation of NOD-like receptor protein 3(NLRP3) inflammasome leads to the elevation of inflammatory factors. There is also new understanding of the pathogenesis and treatment of cardiovascular diseases in TCM. The heat-toxicity theory in cardiovascular diseases and the therapeutic principle of clearing heat and removing toxin have attracted attention. The clinical and pharmacological studies on the treatment of cardiovascular diseases such as Huanglian Jiedu Decoction and Simiao Yong'an Decoction are also gradually increasing. The present study analyzed the common features of the inflammatory response mechanisms in diverse cardiovascular diseases and discussed the significance of the prevention and treatment of diverse cardiovascular diseases by the treatment method of clearing heat and removing toxin to regulate inflammation, which is expected to provide new ideas and references for clinical treatment and drug research on cardiovascular diseases with the same treatment method for different diseases.

Background: Ferroptosis has attracted increasing interest in cancer therapy. Emerging evidences suggest that naturally occurring naphthoquinones exhibit potent anti-glioma effects via various mechanisms., Methods: The anti-glioma effects of plumbagin were evaluated by in vitro and in vivo experiments. Anti-glioma mechanism of plumbagin was studied by proteomics, flow cytometry, MDA assay, western blot, and RT-PCR. Gene knockdown/overexpression, molecular docking, PharmMappper database, and coimmunoprecipitation were used to study the targets of plumbagin., Results: Plumbagin showed higher blood-brain barrier penetration ability than that of lapachol and shikonin and elicited significant growth inhibitory effects in vitro and in vivo. Ferroptosis was the main mechanism of plumbagin-induced cell death. Mechanistically, plumbagin significantly downregulated the protein and mRNA levels of xCT and decreased GPX4 protein levels. NAD(P)H quinone dehydrogenase 1 (NQO1) was revealed as a plumbagin predictive target using PharmMappper database and molecular docking. Plumbagin enhanced NQO1 activity and decreased xCT expression, resulting in NQO1-dependent cell death. It also induced GPX4 degradation via the lysosome pathway and caused GPX4-dependent cell death., Conclusions: Plumbagin inhibited in vitro and in vivo glioma growth via targeting NQO1/GPX4-mediated ferroptosis, which might be developed as a novel ferroptosis inducer or anti-glioma candidate., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Interleukin-37b (hereafter called IL-37) was identified as fundamental inhibitor of natural and acquired immunity. The molecular mechanism and function of IL-37 in colorectal cancer (CRC) has been elusive. Here, we found that IL-37 transgenic (IL-37tg) mice were highly susceptible to colitis-associated colorectal cancer (CAC) and suffered from dramatically increased tumor burdens in colon. Nevertheless, IL-37 is dispensable for intestinal mutagenesis, and CRC cell proliferation, apoptosis, and migration. Notably, IL-37 dampened protective cytotoxic T cell-mediated immunity in CAC and B16-OVA models. CD8 + T cell dysfunction is defined by reduced retention and activation as well as failure to proliferate and produce cytotoxic cytokines in IL-37tg mice, enabling tumor evasion of immune surveillance. The dysfunction led by IL-37 antagonizes IL-18-induced proliferation and effector function of CD8 + T cells, which was dependent on SIGIRR (single immunoglobulin interleukin-1 receptor-related protein). Finally, we observed that IL-37 levels were significantly increased in CRC patients, and positively correlated with serum CRC biomarker CEA levels, but negatively correlated with the CD8 + T cell infiltration in CRC patients. Our findings highlight the role of IL-37 in harnessing antitumor immunity by inactivation of cytotoxic T cells and establish a new defined inhibitory factor IL-37/SIGIRR in cancer-immunity cycle as therapeutic targets in CRC., (© 2021. The Author(s).)

Herein, a nanozyme-mediated ratiometric fluorescence immunoassay for histamine (HA) has been developed. Prussian blue nanoparticles (PBNPs) with outstanding peroxidase-like activity were labelled with goat anti-mouse IgG via a facile electrostatic adsorption to yield the nanozyme-antibody conjugate which acted as a bridge to link the ratiometric fluorescence readout with HA concentration. As substrate, o-phenylenediamine (OPD) was oxidized into 2,3-diaminophenazine (oxOPD) by H 2 O 2 under the catalysis of PBNPs, producing a novel emission at 570 nm and quenching the fluorescence of carbon dots (CDs) at 450 nm simultaneously. Under optimal conditions, the ratio of fluorescence intensity at 570 nm and 450 nm (I 570 /I 450 ) linearly correlated with HA concentration ranging from 1.6 ng/mL to 125 μg/mL, with a detection limit (LOD) of 1.2 ng/mL. In addition, analytical performances including specificity, accuracy and applicability were evaluated, which revealed that this ratiometric fluorescence immunoassay affords an effective platform for sensitive and accurate detection of HA., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world and the third leading cause of cancer-related death. Although the diagnostic scheme of HCC is currently undergoing refinement, the prognosis of HCC is still not satisfactory. In addition to certain factors, such as tumor size and number and vascular invasion displayed on traditional imaging, some histopathological features and gene expression parameters are also important for the prognosis of HCC patients. However, most parameters are based on postoperative pathological examinations, which cannot help with preoperative decision-making. As a new field, radiomics extracts high-throughput imaging data from different types of images to build models and predict clinical outcomes noninvasively before surgery, rendering it a powerful aid for making personalized treatment decisions preoperatively., Objective: This study reviewed the workflow of radiomics and the research progress on magnetic resonance imaging (MRI) radiomics in the diagnosis and treatment of HCC., Methods: A literature review was conducted by searching PubMed for search of relevant peer-reviewed articles published from May 2017 to June 2021.The search keywords included HCC, MRI, radiomics, deep learning, artificial intelligence, machine learning, neural network, texture analysis, diagnosis, histopathology, microvascular invasion, surgical resection, radiofrequency, recurrence, relapse, transarterial chemoembolization, targeted therapy, immunotherapy, therapeutic response, and prognosis., Results: Radiomics features on MRI can be used as biomarkers to determine the differential diagnosis, histological grade, microvascular invasion status, gene expression status, local and systemic therapeutic responses, and prognosis of HCC patients., Conclusion: Radiomics is a promising new imaging method. MRI radiomics has high application value in the diagnosis and treatment of HCC., 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 Gong, Tao, Wu, Liu, Yu, Wang, Zheng, Liu, Huang, Li, Yang, Wei, Yang and Zhang.)

Previous research into the inflammatory cell infiltrate of chronic hyperplastic candidosis (CHC) determined that the immune response is primarily composed of T cells, the majority of which are T helper (CD4 + ) cells. This present investigation used immunohistochemistry to further delineate the inflammatory cell infiltrate in CHC. Cells profiled were those expressing IL-17A cytokine, EBI3 and IL-12A subunits of the IL-35 cytokine, and FoxP3 + cells. Squamous cell papilloma (with Candida infection) and oral lichen planus tissues served as comparative controls to understand the local immune responses to Candida infection. The results demonstrated that Candida- induced inflammation and immune regulation co-exist in the oral mucosa of CHC and that high prevalence of cells expressing the EBI3 cytokine subunit may play an important role in this regulation. This balance between inflammation and immune tolerance toward invading Candida in the oral mucosa may be critical in determining progress of infection.

Neuropathic pain (NeuP) is an important clinical problem accompanying negative mood symptoms. Neuroinflammation in the amygdala is critically involved in NeuP, and the dopamine (DA) system acts as an important endogenous anti-inflammatory pathway. Electroacupuncture (EA) can improve the clinical outcomes in NeuP, but the underlying mechanisms have not been fully elucidated. This study was designed to assess the effectiveness of EA on pain and pain-related depressive-like and anxiety-like behaviors and explore the role of the DA system in the effects of EA. Male Sprague-Dawley rats were subjected to the chronic constrictive injury (CCI) model to induce NeuP. EA treatment was carried out for 30 min once every other day for 3 weeks. The results showed that CCI caused mechanical hyperalgesia and depressive and anxiety-like behaviors in rats and neuroinflammation in the amygdala, such as an increased protein level of TNFα and IL-1β and activation of astrocytes. EA treatment significantly improved mechanical allodynia and the emotional dysfunction induced by CCI. The effects of EA were accompanied by markedly decreased expression of TNFα, IL-1β, and glial fibrillary acid protein (GFAP) in the amygdala. Moreover, EA treatment reversed CCI-induced down-regulation of DA concentration, tyrosine hydroxylase (TH) expression, and DRD1 and DRD2 receptors. These results suggest that EA-ameliorated NeuP may possibly be associated with the DA system to inhibit the neuroinflammation in the amygdala., 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 Zhang, Feng, Pei, Zhang, Chen, Wei, Zhou, Yong and Wang.)

The n -propanol produced by Saccharomyces cerevisiae has a remarkable effect on the taste and flavor of Chinese Baijiu. The n -propanol metabolism-related genes were deleted to evaluate the role in the synthesis of n -propanol to ascertain the key genes and pathways for the production of n -propanol by S. cerevisiae . The results showed that CYS 3, GLY 1, ALD 6, PDC 1, ADH 5, and YML 082 W were the key genes affecting the n -propanol metabolism in yeast. The n -propanol concentrations of α5Δ GLY 1, α5Δ CYS 3, and α5Δ ALD 6 increased by 121.75, 22.75, and 17.78%, respectively, compared with α5. The n -propanol content of α5Δ PDC 1, α5Δ ADH 5, and α5Δ YML 082 W decreased by 24.98, 8.35, and 8.44%, respectively, compared with α5. The contents of intermediate metabolites were measured, and results showed that the mutual transformation of glycine and threonine in the threonine pathway and the formation of propanal from 2-ketobutyrate were the core pathways for the formation of n -propanol. Additionally, YML 082 W played important role in the synthesis of n -propanol by directly producing 2-ketobutyric acid through l-homoserine. This study provided valuable insights into the n -propanol synthesis in S. cerevisiae and the theoretical basis for future optimization of yeast strains in Baijiu making.

Southwestern China is an important ecologically resource area and ecologically fragile area in China, which plays an important role in the national project of "Clear Waters and Green Mountains". Based on land use data set with a 1 km spatial resolution and combined with land use transfer matrix, we analyzed the characteristics and driving forces of land use change in Southwest China from 2000 to 2015. Based on the MODIS remote sensing index, we calculated the vegetation coverage in Southwest China using the dimidiate pixel model, and analyzed the changes of the normalized vegetation index (NDVI) and vegetation coverage. Results showed that the main land types were woodland, cropland and grassland. The built-up land area increased by 5874 km 2 (55.8%), the cropland area decreased by 6211 km 2 , and grassland decreased by 2099 km 2 . From 2000 to 2015, the area that had been changed to built-up land was the largest, mainly from cropland (contributed 68.2%), woodland (contributed 19.2%) and grassland (contributed 13.1%). The transformed areas were mostly close to urban area. The area and rate for the transformation of cropland were 7079 km 2 and 2.2% respectively, accounting for 46.0% of all the transferred out areas. Most of the woodland were transformed from grassland (61.8%), mainly distributed in central and southern Guizhou and western Yunnan. Both NDVI and vegetation coverage were significantly increased, indicating that the whole region was greening. NDVI of both natural vegetation and cropland increased significantly, while the NDVI of areas with expanded build-up land decreased. Therefore, natural vegetation and cropland dominated the vegetation change in this region. Results of the resi-dual analysis showed that both climate change and human activities contributed significantly to the greening trend.

Circular RNAs (circRNAs) play important roles in cancer tumorigenesis and progression, representing prognostic biomarkers and therapeutic targets. In this case, we demonstrated the role of circ-NOLC1 in epithelial ovarian cancer (EOC). Our results have shown that Circ-NOLC1 expression was higher in EOC tissues than in normal tissues, and was positively associated with FIGO stage, differentiation. Among ovarian cancer cell lines, circ-NOLC1 expression was the highest in A2780, and lowest in CAOV3. Overexpression of circ-NOLC1 in CAOV3 cells increased cell proliferation, migration, and invasion ability, whereas silencing of circ-NOLC1 in A2780 cells had the opposite effect: however, neither circ-NOLC1 downregulation nor overexpression influenced NOLC1 mRNA expression. In nude mice with subcutaneous tumors, circ-NOLC1 downregulation decreased tumor growth. Bioinformatic analysis and RNA-binding protein immunoprecipitation showed that circ-NOLC1 could bind to ESRP1. In addition, the overexpression of circ-NOLC1 significantly increased ESRP1, RhoA, and CDK1 protein and mRNA expression level; circ-NOLC1 downregulation had the opposite effects. The tumor-promoting effect of circ-NOLC1 was inhibited by knockdown of ESRP1, CDK1, or RhoA expression in circ-NOLC1-overexpressing cells, which might act by modulating RhoA and CDK1 expression. In conclusion, our study demonstrated that Circ-NOLC1 might promote EOC tumorigenesis and development by binding ESRP1 and modulating CDK1 and RhoA expression.

Intraspecific male polymorphism exhibiting extreme differences in morphology, behavior and life history presents good opportunities to explore adaptation mechanisms to different environments. In this study, we examined the transcriptomic differences between wingless and winged morphs of a fig wasp species Philotrypesis tridentata to investigate molecular basis to maintain polymorphisms. The winged male adults fly outside fig syconia to mate, while the wingless only stay and mate inside fig syconia where they have developed. We identified 2,391 differentially expressed genes (DEGs) with 1,396 highly expressed in winged morphs and 995 in wingless morphs. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses on the DEGs and differential alternative splicing genes and analyzed the top ten DEGs with the highest differential expression in each morph. The results showed that genes related to biosynthesis processes, lipid metabolism, energy production, flight and defense of the complex environments outside fig syconia were up-regulated in winged morphs. Genes involved in substance and energy metabolism and chemical reception were up-regulated in wingless morphs which might relate to their living inside fig syconia. The differences in highly expressed genes between two morphs prove adaptation of P. tridentata male polymorphism to different living environments., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Butyrate acts as a regulator in multiple inflammatory organ injuries. However, the role of butyrate in acute liver injury has not yet been fully explored. In the present study, we aimed to investigate the association between butyrate and lipopolysaccharide (LPS)-induced acute liver injury and the signaling pathways involved., Methods: LPS-induced acute liver injury was induced by intraperitoneal injection of LPS (5 mg/kg) in G-protein-coupled receptor 43 (GPR43)-knockout (KO) and wild-type female C57BL/6 mice. Sodium butyrate (500mg/kg) was administered intraperitoneally 30 min prior to LPS exposure. Liver injury was detected by serum markers, tissue morphology, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). Pro-inflammatory-factor levels were detected by enzyme-linked immunosorbent assay and real-time polymerase chain reaction (RT-PCR). Cell models were first treated with sodium butyrate (4 μmol/mL), followed by LPS (1 μg/mL) half an hour later in GPR43 small interfering RNA (siRNA)-transfected or control RAW264.7 cells. Cell-inflammation status was evaluated through detecting pro-inflammatory-factor expression by RT-PCR and also through checking toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB)-element levels including TLR4, TRAF6, IKKβ, IкBα, phospho-IкBα, p65, and phospho-p65 by Western blot. The interaction between GPR43 and β-arrestin-2 was tested by co-immunoprecipitation., Results: Sodium butyrate reversed the LPS-induced tissue-morphology changes and high levels of serum alanine aminotransferase, aspartate transaminase, myeloperoxidase, TUNEL, and pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin-6. The ameliorating effect of sodium butyrate was weakened in GPR43-KO mice and GPR43 siRNA RAW264.7 cells, compared with those of GPR43-positive controls. Sodium butyrate downregulated some elements of the TLR4/NF-κB pathway, including phospho-IκBα and phospho-p65, in RAW264.7 cells. Increased interactions between GPR43 and β-arrestin-2, and between β-arrestin-2 and IкBα were observed., Conclusion: Sodium butyrate significantly attenuated LPS-induced liver injury by reducing the inflammatory response partially via the GPR43/β-arrestin-2/NF-κB signaling pathway., (© The Author(s) 2020. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University.)

The higher alcohols produced by Saccharomyces cerevisiae exert remarkable influence on the taste and flavour of Chinese Baijiu. In order to study the regulation mechanism of amino acid metabolism genes on higher alcohol production, eight recombinant strains with amino acid metabolism gene deletion were constructed. The growth, fermentation performance, higher alcohol production, and expression level of genes in recombinant and original α 5 strains were determined. Results displayed that the total higher alcohol concentration in α 5 ΔGDH1 strain decreased by 27.31% to 348.68 mg/L compared with that of α 5. The total content of higher alcohols in α 5 ΔCAN1 and α 5 ΔGAT1 strains increased by 211.44% and 28.36% to 1493.96 and 615.73 mg/L, respectively, compared with that of α 5. This study is the first to report that the CAN1 and GAT1 genes have great influence on the generation of higher alcohols. The results demonstrated that amino acid metabolism plays a substantial role in the metabolism of higher alcohols by S. cerevisiae. Interestingly, we also found that gene knockout downregulated the expression levels of the knocked out gene and other genes in the recombinant strain and thus affected the formation of higher alcohols by S. cerevisiae . This study provides worthy insights for comprehending the metabolic mechanism of higher alcohols in S. cerevisiae for Baijiu fermentation., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020 Ya-Ping Wang et al.)

Thirteen typical antibiotics in surface water of the Lianhua Reservoir were analyzed using HPLC/MS/MS to assess the pollution characteristics and risk levels. Ten antibiotics except for erythromycin, sulfadiazine, and sulfamethoxazole were detected in surface water and the total concentration of antibiotics varied between non-detectable (n.d.) and 925.26 ng ·L -1 . Azithromycin had the highest concentration (n.d.-232.61 ng ·L -1 ) with the detection frequency of 75%, followed by enrofloxacin (n.d.-187.69 ng ·L -1 ), tetracycline (n.d.-155.05 ng ·L -1 ), and ciprofloxacin (n.d.-83.66 ng ·L -1 ) with the detection frequencies over 60%. The spatial distribution of antibiotics was as follows: total concentration of upstream (sampling point 1) > Aoxi River stream tributary (sampling point 2) > reservoir downstream (sampling point 3) > reservoir entrance (sampling point 4) > reservoir area (sampling point 5). The seasonal variations in the concentrations of antibiotics were evident; total concentrations in the dry season were significantly higher than those in the wet and normal seasons. The results of the environmental risk assessment indicated that ofloxacin, enrofloxacin, and ciprofloxacin pose significant risks to the environment. In the Lianhua Reservoir, ciprofloxacin showed high potential risk to the ecological environment, while the environmental risks of other antibiotics in the reservoir were below the medium level. The combined risk value of the antibiotics in the dry season was higher than that in the wet and normal seasons.

The innate immunity is the most important defense against pathogen of insects, and the peptidoglycan recognition proteins (PGRPs) play an important role in the processes of immune recognition and initiation of Toll, IMD and other signal pathways. In fig wasps, pollinators and non-pollinators present different evolutionary histories and lifestyles, even though both are closely associated with fig syconia, which may indicate their different patterns in the evolution of PGRPs. By manual annotation, we got all the PGRP genes of 12 fig wasp species, containing seven pollinators and five non-pollinators, and investigated their putative different evolutionary patterns. We found that the number of PGRP genes in pollinators was significantly lower than in non-pollinators, and the number of catalytic PGRP presented a declining trend in pollinators. More importantly, PGRP-SA is associated with initiating the Toll pathway, as well as gram-negative bacteria-binding proteins (GNBPs), which were completely lost in pollinators, which led us to speculate that the initiation of Toll pathway was simpler in pollinators than in non-pollinators. We concluded that fig pollinators owned a more streamlined innate immune recognition system than non-pollinators. Our results provide molecular evidence for the adaptive evolution of innate immunity in insects of host specificity.

Background: The cellular immunity of lung cancer patients is mainly the immune response of T cells, which plays an important role in tumour cell killing and immune surveillance. Transforming growth factor 1 (TGF-β1) is secreted by tumour cells that can suppress the immune response and is an important group of immune down-regulation factors. Our study aims to investigate the effect of TGF-β1 on the morphology and cellular immune function of A549 and peripheral blood mononuclear cells (PBMCs)., Methods: A549 cell line was cultured, PBMCs were cultured with different concentrations of TGF-β1, and the morphology of A549 cells and PBMCs were seen. The levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IFN-γ, and TNF and the numbers of CD3, CD4, CD8, CD4/CD8, and CD3 CD25 and CD4 CD25 in PBMCs were detected., Results: During co-culture of A549 with PBMCs, TGF-β1 can induced A549 showing epithelial-to-mesenchymal transition, enhanced its ability of migration and infiltration. Simultaneously, TGF-β1 can depressing the growth and proliferation of PBMCs, inhibiting T-cell activation, and accelerating the PBMCs apoptosis. TGF-β1 can inhibits A549 Th1 related-cytokines, enhance Th2 related-cytokines, cause the disorder of Th1/Th2, resulting in the Th1 cellular dominate immunity decline., Conclusions: TGF-β1 may affect the secretion of related cytokines, hinder the activation of T lymphocytes, destroy the immune surveillance and killing effect of the body, and thus inhibit the cellular immunity., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-4437). The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

Although the bioavailability and stability of curcumin can be greatly improved by liposomes encapsulation, its application is still limited due to the short circulating time. In this present work, we aim to construct a long-circulating delivery system of liposomal curcumin (Cur-Lips) by coating bovine serum albumin (BSA), namely, BSA-coated liposomal curcumin (BSA-Cur-Lips). The effects of coating albumin on the physicochemical properties of Cur-Lips were investigated. It was found that BSA-Cur-Lips was more spherical, more homogeneous in size, and significantly larger than Cur-Lips. Combining sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), Coomassie bright blue staining, and X-ray photoelectron spectroscopy analysis (XPS), we confirmed that albumin molecules were stably located on the surface of BSA-Cur-Lips. In addition, the impacts of the coating albumin on the Cur-Lips release and phagocytosis by mouse macrophages Raw264.7 in vitro were investigated. We found that no significant initial burst drug release effect was observed for both Cur-Lips and BSA-Cur-Lips and the presence of albumin can enhance the liposome structure stability and slow down the release of Cur. More importantly, the macrophage phagocytosis of Cur-Lips was significantly reduced after coating albumin. In conclusion, coating albumin is a promising approach for developing a long-circulating delivery system of liposomal curcumin, and its properties including low phagocytosis, slow drug release, enhanced stability, and nontoxicity give this system great prospects for practical use., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)