Inferring Mycobacterium Tuberculosis Drug Resistance and Transmission using Whole-genome Sequencing in a High TB-burden Setting in China.

Objective: China is among the 30 countries with a high burden of tuberculosis (TB) worldwide, and TB remains a public health concern. Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China. However, molecular epidemiological studies of Kashgar are lacking. Methods: A population-based retrospective study was conducted using whole-genome sequencing (WGS) to determine the characteristics of drug resistance and the transmission patterns. Results: A total of 1,668 isolates collected in 2020 were classified into lineages 2 (46.0%), 3 (27.5%), and 4 (26.5%). The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid (7.4%, 124/1,668), streptomycin (6.0%, 100/1,668), and rifampicin (3.3%, 55/1,668). The rate of rifampicin resistance was 1.8% (23/1,290) in the new cases and 9.4% (32/340) in the previously treated cases. Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains, respectively: 18.6% vs. 8.7 or 9%, P < 0.001. The estimated proportion of recent transmissions was 25.9% (432/1,668). Multivariate logistic analyses indicated that sex, age, occupation, lineage, and drug resistance were the risk factors for recent transmission. Despite the low rate of drug resistance, drug-resistant strains had a higher risk of recent transmission than the susceptible strains (adjusted odds ratio, 1.414; 95% CI, 1.023-1.954; P = 0.036). Among all patients with drug-resistant tuberculosis (DR-TB), 78.4% (171/218) were attributed to the transmission of DR-TB strains. Conclusion: Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.

Intensive Lipid-Lowering Therapy as per the Latest Dyslipidemia Management Guideline in Predicting Favorable Long-Term Clinical Outcomes in Patients Undergoing Coronary Artery Bypass Grafting: A Retrospective Cohort Study.

Background There are limited data on low-density lipoprotein cholesterol (LDL-C) goal achievement per the 2019 European Society of Cardiology/European Atherosclerosis Society dyslipidemia management guidelines and its impact on long-term outcomes in patients undergoing coronary artery bypass grafting (CABG). We investigated the association between LDL-C levels attained 1 year after CABG and the long-term outcomes. Methods and Results A total of 2072 patients diagnosed with multivessel coronary artery disease and undergoing CABG between 2011 and 2020 were included. Patients were categorized by lipid levels at 1 year after CABG, and the occurrence of major adverse cardiovascular and cerebrovascular events (MACCEs) was evaluated. The goal of LDL-C <1.40 mmol/L was attained in only 310 patients (14.9%). During a mean follow-up of 4.2 years after the index 1-year assessment, 25.0% of the patients experienced MACCEs. Multivariable-adjusted hazard ratios (95% CIs) for MACCEs, cardiac death, nonfatal myocardial infarction, nonfatal stroke, revascularization, and cardiac rehospitalization were 1.94 (1.41-2.67), 2.27 (1.29-3.99), 2.45 (1.55-3.88), 1.17 (0.63-2.21), 2.47 (1.31-4.66), and 1.87 (1.19-2.95), respectively, in patients with LDL-C ≥2.60 mmol/L, compared with patients with LDL-C <1.40 mmol/L. The LDL-C levels at 1-year post-CABG were independently associated with long-term MACCEs. Conclusions This retrospective analysis demonstrates that lipid goals are not attained in the vast majority of patients at 1 year after CABG, which is independently associated with the increased risk of long-term MACCEs. Further prospective, multicenter studies are warranted to validate if intensive lipid management could improve the outcomes of patients undergoing CABG.

Cationic N,S-chelate half-sandwich iridium complexes: synthesis, characterization, anticancer and antiplasmodial activity.

A series of pyrazole-based ligands and their corresponding cationic N,S-chelate half-sandwich iridium complexes were successfully synthesized. All iridium complexes exhibited good anticancer activity against the MCF-7 and MDA-MB-231 human breast cancer cells. The cytotoxic activity of unsubstituted iridium complex 1 is greater than that of cisplatin against MCF-7 cells. In addition, the cationic half-sandwich iridium complexes are also efficient in antiplasmodial study and complex 1 displayed the best activity as its IC50 was observed to be approximately 0.11 µM against the CQS-NF54 strain. These iridium complexes generally exhibited enhanced activity against the CQS-NF54 strain in comparison with that against the CQR-K1 strain. An "IC50 speed assay" investigation against the CQS-NF54 strain indicated complexes 1-3 to be fast-acting complexes that reach their lowest IC50 values within 16 hours. All complexes were fully characterized by IR spectroscopy, NMR spectroscopy, and elemental analysis, and the structure of the iridium complex was confirmed by single-crystal X-ray diffraction.

Half-sandwich iridium complexes with hydrazone ligands: preparation, structure, and catalytic synthesis of cyanosilylethers under air.

A series of hydrazone-based N,O-chelate half-sandwich iridium complexes were synthesized through a facile route with good yields. These air- and moisture-stable iridium complexes exhibited excellent catalytic activity in the cyanosilylether synthesis under mild reaction conditions. Under the catalysis of iridium, various cyanosilylethers with different substituents were obtained through a one-pot reaction of trimethylsilyl cyanide (TMSCN) with carbonyl substrates, with good to excellent yields. The excellent catalytic efficiency, wide substrate range, and mild reaction conditions made this type of iridium catalyst have the potential for industrial applications. All the half-sandwich iridium complexes were well characterized by IR, NMR, and EA analyses. The molecular structure of iridium complex 1 was confirmed by single-crystal X-ray analysis.

Half-Sandwich Ruthenium Complexes with Hydrazone Ligands: Preparation, Structure, and Catalytic Activity in Cyanosilylether Synthesis under an Air Atmosphere.

A new class of N,O-coordinate half-sandwich ruthenium complexes supported by hydrazone ligands with a general formula of [Ru(η6-p-cymene)Cl(L)] have been obtained in moderate to excellent yields conveniently. These air- and moisture-stable ruthenium complexes exhibited excellent catalytic activity in cyanosilylether synthesis under mild reaction conditions. Under the catalysis of ruthenium, various cyanosilylethers with different substituents were obtained through a one-pot reaction of trimethylsilyl cyanide with carbonyl substrates, with good to excellent yields. Excellent catalytic efficiency, a wide substrate range, and mild reaction conditions made this type of ruthenium catalyst have potential for industrial application. All of the half-sandwich ruthenium complexes have been well described by infrared, nuclear magnetic resonance, and EA analysis. Molecular structures of ruthenium complexes 1 and 4 were confirmed by single-crystal X-ray analysis.

A bibliometric analysis of hotpots and trends for the relationship between skin inflammation and regeneration.

Background: Skin regeneration is a challenging issue worldwide. Increasing research has highlighted the role of immune cells in healing and the underlying regulatory mechanism. The purpose of this study was to identify the hotspots and trends in skin regeneration and inflammation research through bibliometrics and to provide insights into the future development of fundamental research and disease treatment. Methods: Publications were collected from the Web of Science Core Collection on March 1, 2022. Articles and reviews published in English from January 1, 1999, to December 31, 2022, were selected, and statistical analyses of countries, institutions, authors, references, and keywords were performed using VOSviewer 1.6.18 and CiteSpace 5.8. Results: A total of 3,894 articles and reviews were selected. The number of publications on skin inflammation and regeneration showed an increasing trend over time. Additionally, authors and institutions in the United States, United Kingdom, Canada, and China appeared to be at the forefront of research in the field of skin inflammation and regeneration. Werner Sabine published some of the most cited papers. Wound Repair and Regeneration was the most productive journal, while Journal of Investigative Dermatology was the most cited journal. Angiogenesis, diamonds, collagen, cytokine, and keratinocytes were the five most commonly used keywords. Conclusion: The number of publications on skin inflammation and regeneration show an increasing trend. Moreover, a series of advanced technologies and treatments for skin regeneration, such as exosomes, hydrogels, and wound dressings, are emerging, which will provide precise information for the treatment of skin wounds. This study can enhance our understanding of current hotspots and future trends in skin inflammation and regeneration research, as well as provide guidelines for fundamental research and clinical treatment.

Genome-wide analysis of AP2/ERF superfamily in Isatis indigotica.

OBJECTIVE: AP2/ERF (APETALA2/ethylene-responsive factor) superfamily is one of the largest gene families in plants and has been reported to participate in various biological processes, such as the regulation of biosynthesis of active lignan. However, few studies have investigated the genome-wide role of the AP2/ERF superfamily in Isatis indigotica. This study establishes a complete picture of the AP2/ERF superfamily in I. indigotica and contributes valuable information for further functional characterization of IiAP2/ERF genes and supports further metabolic engineering. METHODS: To identify the IiAP2/ERF superfamily genes, the AP2/ERF sequences from Arabidopsis thaliana and Brassica rapa were used as query sequences in the basic local alignment search tool. Bioinformatic analyses were conducted to investigate the protein structure, motif composition, chromosome location, phylogenetic relationship, and interaction network of the IiAP2/ERF superfamily genes. The accuracy of omics data was verified by quantitative polymerase chain reaction and heatmap analyses. RESULTS: One hundred and twenty-six putative IiAP2/ERF genes in total were identified from the I. indigotica genome database in this study. By sequence alignment and phylogenetic analysis, the IiAP2/ERF genes were classified into 5 groups including AP2, ERF, DREB (dehydration-responsive element-binding factor), Soloist and RAV (related to abscisic acid insensitive 3/viviparous 1) subfamilies. Among which, 122 members were unevenly distributed across seven chromosomes. Sequence alignment showed that I. indigotica and A. thaliana had 30 pairs of orthologous genes, and we constructed their interaction network. The comprehensive analysis of gene expression pattern in different tissues suggested that these genes may play a significant role in organ growth and development of I. indigotica. Members that may regulate lignan biosynthesis in roots were also preliminarily identified. Ribonucleic acid sequencing analysis revealed that the expression of 76 IiAP2/ERF genes were up- or down-regulated under salt or drought treatment, among which, 33 IiAP2/ERF genes were regulated by both stresses. CONCLUSION: This study undertook a genome-wide characterization of the AP2/ERF superfamily in I. indigotica, providing valuable information for further functional characterization of IiAP2/ERF genes and discovery of genetic targets for metabolic engineering.

Diastereoselective Synthesis of Chromeno[3,2-d]isoxazoles via Brønsted Acid Catalyzed Tandem 1,6-Addition/Double Annulations of o-Hydroxyl Propargylic Alcohols.

A Brønsted acid catalyzed tandem process to access densely functionalized chromeno[3,2-d]isoxazoles with good to excellent yields and diastereoselectivities was disclosed. The procedure is proposed to involve a 1,6-conjugate addition/electrophilic addition/double annulations process of alkynyl o-quinone methides (o-AQMs) in situ generated from o-hydroxyl propargylic alcohols with nitrones. Mild conditions, good functional group compatibility, easy scale-up of the reaction, and further product transformation demonstrated its potential application.

Half-Sandwich Iridium Complexes with Hydrazone Ligands: Synthesis and Catalytic Activity in N-Alkylation of Anilines or Nitroarenes with Alcohols via Hydrogen Autotransfer.

Here, we synthesize a series of hydrazone-based N,O-chelate half-sandwich iridium complexes through a facile route. All air-stable iridium complexes show high catalytic activity in N-alkylation of a broad scope of aniline derivatives and alcohols with liberating water as the sole byproduct. This reaction provides a smooth route to synthesize diverse monoalkylated amines in good to excellent yields at moderate temperature with a low catalyst loading. Moreover, the challenging N-alkylation process using nitroarene substrates as coupling partners is also carried out in this catalytic system. The mechanistic study shows that the present iridium catalysis process proceeds through a hydrogen borrowing mechanism. All iridium(III) complexes 1-4 are characterized by infrared (IR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and elemental analysis.

One-pot catalyst-free synthesis of benzopyrroxazine derivatives by a mutually activated sequential annulation process.

A one-pot catalyst-free reaction of o-hydroxyaryl azomethine ylides, vinyl pyridines and paraformaldehyde for the synthesis of benzopyrroxazines is reported, which offers a straightforward and atom-economical procedure for the preparation of benzopyrroxazine derivatives in moderate to excellent yields under mild conditions. A self-catalyzed [3 + 2] annulation through a mutual activation method and a sequential non-catalyzed [5 + 1] annulation process contribute to this strategy. The corresponding control experiments have been conducted to reveal the mechanism of this reaction.

Synthesis, Structure, and Catalytic Hydrogenation Activity of [NO]-Chelate Half-Sandwich Iridium Complexes with Schiff Base Ligands.

A series of N,O-coordinate iridium(III) complexes with a half-sandwich motif bearing Schiff base ligands for catalytic hydrogenation of nitro and carbonyl substrates have been synthesized. All iridium complexes showed efficient catalytic activity for the hydrogenation of ketones, aldehydes, and nitro-containing compounds using clean H2 as reducing reagent. The iridium catalyst displayed the highest TON values of 960 and 950 in the hydrogenation of carbonyl and nitro substrates, respectively. Various types of substrates with different substituted groups afforded corresponding products in excellent yields. All N,O-coordinate iridium(III) complexes 1-4 were well characterized by IR, NMR, HRMS, and elemental analysis. The molecular structure of complex 1 was further characterized by single-crystal X-ray determination.

Synthesis and Optoelectronic Properties of Cationic Iridium(III) Complexes with o-Carborane-Based 2-Phenyl Benzothiazole Ligands.

A series of cationic cyclometalated iridium(III) complexes with o-carborane cage on the main ligand of 2-phenylbenzothiazole were synthesized. The prepared iridium complexes (C1-C6) were fully characterized by UV-vis, NMR, and FT-IR spectra. The exact molecular structure of complex C1 was further studied by single crystal X-ray diffraction analysis. The different substitution position of o-carborane on the 2-phenylbenzothiazole ring lead to obvious differences in the emission properties of the synthesized complexes. The o-carboranyl unit results in a bathochromic shift of 10 nm in the fluorescence emission spectrum of C2. In addition, the presence of an o-carborane fragment promoted the strong fluorescence intensity of C1 and C4, which can be used as a tool to effectively boost the intensity of fluorescence properties. The emission fluorescent behavior of iridium(III) complexes can be facilely tuned by structural variations in the main ligands of these materials.

KRT7 promotes epithelial­mesenchymal transition in ovarian cancer via the TGF­ß/Smad2/3 signaling pathway.

Keratin 7 (KRT7) is a member of the keratin gene family. KRT7 is abnormally expressed in various types of cancer and promotes the malignant progression of tumors. However, the role of KRT7 in ovarian cancer remains unclear. The present study aimed to validate the role of KRT7 in ovarian cancer progression. KRT7 expression levels in patients with ovarian cancer were analyzed using data obtained from the Human Protein Atlas and The Cancer Genome Atlas databases. KRT7 mRNA and protein expression levels were upregulated in ovarian cancer tissue compared with normal tissue. KRT7 expression was associated with the grading, staging and poor prognosis of ovarian cancer. The differentially expressed genes affected by KRT7 were primarily enriched in the functions of cell migration, cell adhesion and cell growth. In vitro studies, including a CCK8 assay, were used to detect cell proliferation. In addition, wound healing and transwell assays were performed to analyze cell migration. The results demonstrated that KRT7 overexpression was associated with increased proliferation, migration and epithelial­mesenchymal transition (EMT) of ovarian cancer cells, and the migration and EMT of ovarian cancers cells were decreased following knockdown with KRT7 small interfering RNA. In vivo, knockdown of KRT7 inhibited tumor growth of ovarian cancer. Furthermore, KRT7 regulated EMT in ovarian cancer via the TGF­ß/Smad2/3 pathway, and regulated cell­matrix adhesion through integrin­ß1­focal adhesion kinase signaling. These results suggest that KRT7 may be a potential molecular marker for prognosis prediction in patients with ovarian cancer.

Research Progress on Developmental Biology of Sarcosaprophagous Insects. / å—œå°¸æ€§æ˜†è™«å‘è‚²ç”Ÿç‰©å­¦ç ”ç©¶è¿›å±•.

Forensic entomology provides a feasible way to estimate postmortem interval (PMI), of which the growth and development of sarcosaprophagous insects is the most widely used indicator in forensic practice. Over the years, forensic entomologists have carried out a large number of studies on the development biology of sarcosaprophagous insects. This paper illustrates the main factors that affect the development of sarcosaprophagous insects, including temperature, humidity, light, food types and poisons. The development indicators of sarcosaprophagous insects were reviewed from the perspectives of morphology, differential gene expression and biochemical characteristics. It is emphasized that future research of development biology on sarcosaprophagous insects should fully absorb and integrate the methods of artificial intelligence and omics, and the research object also needs further expansion in order to establish a more objective and more accurate PMI estimation method.

MOFs assembled from C3 symmetric ligands: structure, iodine capture and role as bifunctional catalysts towards the oxidation-Knoevenagel cascade reaction.

Three new NiII/CoII-metal organic frameworks were self-assembled by the reaction of C3 symmetric 1,3,5-tribenzoic acid (H3BTC) and 2,4,6-tris(4-pyridyl)-1,3,5-triazine (4-TPT) ligands and NiII/CoII salts under solvothermal conditions. Isomorphous MOF1 and MOF2 exhibit a 3D pillar-layer framework based on binuclear M2(OH)(COO)2 units connected by tritopic BTC3- and 4-TPT ligands with a novel (3,5)-connected topology net. MOF3 displays a 3-fold interpenetrated 3D network exhibiting a (3,4)-connected topology net. The porous MOF3 can reversibly take up I2. The activated MOFs contain both Lewis acid (NiII center) and basic (uncoordinated pyridyl or carboxylic groups) sites, and act as bifunctional acid-base catalysts. The catalytic measurements demonstrate that the activated MOF3 exhibits good activities for benzyl alcohol oxidation and the Knoevenagel reaction and can be recycled and reused for at least four cycles without losing its structural integrity and high catalytic activity. Thus, the catalytic properties for the oxidation-Knoevenagel cascade reaction have also been studied.

Half-Sandwich Iridium Complexes for the One-Pot Synthesis of Amides: Preparation, Structure, and Diverse Catalytic Activity.

Several types of air-stable N,O-coordinate half-sandwich iridium complexes containing Schiff base ligands with the general formula [Cp*IrClL] were synthesized in good yields. These stable iridium complexes displayed a good catalytic efficiency in amide synthesis. A variety of amides with different substituents were obtained in a one-pot procedure with excellent yields and high selectivities through the amidation of aldehydes with NH2OH·HCl and nitrile hydration under the catalysis of complexes 1-4. The excellent and diverse catalytic activity, mild conditions, broad substance scope, and environmentally friendly solvent make this system potentially applicable in industrial production. Half-sandwich iridium complexes 1-4 were characterized by NMR, elemental analysis, and IR techniques. Molecular structures of complexes 2 and 3 were confirmed by single-crystal X-ray analysis.

A novel ratiometric fluorescent probe for the detection of uric acid in human blood based on H2O2-mediated fluorescence quenching of gold/silver nanoclusters.

In this work, a ratiometric fluorescent probe (RF-probe) for highly sensitive and selective detection of uric acid was reported for the first time toward H2O2 based on inner filter effect (IFE) between bimetallic gold/silver nanoclusters (Au/Ag NCs) and 2,3-diaminophenazine (DAP). For this RF-probe, uric acid was degraded to allantoin and H2O2. Upon the addition of HRP, o-phenylenediamine (OPD) could be catalytically oxidized to DAP in the presence of H2O2, then the fluorescence intensity corresponding to DAP at 580 nm increased dramatically with a fluorescence quenching of BSA-Au/Ag NCs at 690 nm, resulting in a RF-probe toward uric acid. This RF-probe allowed for the sensitive detection of uric acid in range of 5.0 × 10-6 M to 5.0 × 10-5 M with a detection limit (S/N = 3) as low as 5.1 × 10-6 M. At the same time, it has been successfully used for uric acid levels detection in human serum, and the results are consistent with those of the hospital. RF-probe built may provide a ratiometric fluorescence universal platform for detection of various species involving in the production of H2O2 in other biological systems.

A highly sensitive signal-amplified gold nanoparticle-based electrochemical immunosensor for dibutyl phthalate detection.

A simple and signal-amplified, label-free electrochemical impedimetric immunosensor for dibutyl phthalate (DBP), a type of phthalate ester, was developed using gold nanoparticles (AuNPs) induced signal amplification. The approach was based on an indirectly competitive binding system of coating antigen that coated on antigen/chitosan/MWCNTs@GONRs/GCE (modified electrodes), target (DBP) and anti-DBP antibody. Signal amplification was performed via the enlargement of AuNPs through NADH-promoted catalytic precipitation, which caused a marked increase in the electron-transfer resistance and electrostatic repulsion after an AuNP-labeled second antibody conjugated to anti-DBP. Under the optimized conditions, this method displayed: (i) low detection limits (7ng/mL, 10 times lower than the traditional ELISA method using the same antibody); (ii) satisfactory accuracy (recoveries, 86.0-120.4%) and agreement with corresponding ELISA method; (iii) high tolerance to some environmental interferents; and (iv) low cost and low sample consumption (6µL). Our results demonstrate the great potential and high efficiency of this immunosensor in practical applications for the cost-effective and sensitive monitoring of DBP in aquatic environments.