As an important aminoglycosides antibiotic, gentamicin has been used clinically over decades. With the development in modern biological technology, the mechanisms of gentamicin action and resistance, its biosynthesis and structural modification were studied in great depth. Meanwhile, its emerging novel bioactivities and potential applications are also under extensive exploration. Here we summarize the latest progresses and prospects towards the future development of gentamicin for more efficient and effective uses.
Aminoglycosides ; biosynthesis ; chemistry ; Gentamicins ; biosynthesis ; chemistry

OBJECTIVE To investigate the transgenerational effect of neuroendocrine metabolic programmed alteration in adult intrauterine growth retardation (lUGR) offspring rats with prenatal nicotine exposure. METHODS Pregnant Wistar rats were administered daily with nicotine (2 mg.kg-1 ) by sc from gestational day 11 until delivery. F1 offspring was fed with a standard diet before four groups in F2 were set up according to the cross-mating between F1 normal adult rats and nicotine-induced lUGR adult rats. CC group was mated by F1 normal adult rats, CN group by F1 normal adult male rats and lUGR adult female rats, NC group by F1 lUGR adult male rats and normal adult female rats, while NN group was mated by F1 lUGR adult rats. F2 adult rats were subjected to a fortnight ice water swimming stimulus. Blood samples were collected before and after stress and then detected for the levels of adrenocortico-tropic hormone ( ACTH), corticosterone ( CORT), glucose, triglycerides ( TG) and total cholesterol (TCH). RESULTS Before stress, the level of serum CORT in F2 male rats of NN group was decreased to 73.9% of that of the CC group (P<0.05),while the level of serum TG in F2 male rats of CN and NC groups was increased to 1.43 and 1.52 times that of the CC group, respectively ( P<0.05). Meanwhile, the level of serum TG in F2 female rats of CN, NC and NN groups was increased to 1.71, 1.80 and 1.81 times that of the CC group, respectively (P<0.05). After stress, the serum CORT gain rate in F2 male rats of CC group was -1.67%, but was 36.0% in NN group. The serum glucose level in male NC group and in female CN group was increased to 1.61 and 1.62 times that of the corresponded CC groups, respectively (P<0.01). Furthermore, the serum TG gain rate in F2 rats of each nicotine group was decreased markedly in comparison with their corresponding controls (P<0.05), ie, the serum TG gain rates in F2 male rats of CN, NC and NN groups were decreased to 46.4%, 16.7% and 7.7% of the CC group, while the serum TG gain rates in F2 female rats of these groups were decreased to 20.6%, 4.0% and 8.4% of the CC group, respectively. Compared with CC group, TCH level of females and males in NN group was decreased by 40.5% and 21.9%(P<0.01) before stress, respectively, and the TCH gain rate of females in NN group was increased by 49.7%(P<0.05) after stress. CONCLUSION The reproductive and developmental toxicities and the neuroendocrine metabolic programming alterations induced by prenatal nicotine exposure are transgenerated to F2 offspring and these effects exhibit gender and parental differences.

Here we tell a 20-year long story. It began with an easily overlooked DNA degradation (Dnd) phenomenon during electrophoresis and eventually led to the discovery of an unprecedented DNA sulfur modification governed by five dnd genes. This unusual DNA modification, called phosphorothioation, is the first physiological modification identified on the DNA backbone, in which the nonbridging oxygen is replaced by sulfur in a sequence selective and stereo-specific manner. Homologous dnd gene clusters have been identified in diverse and distantly related bacteria and thus have drawn immediate attention of the entire microbial scientific community. Here, we summarize the progress in chemical, genetic, enzymatic, bioinformatical and analytical aspects of this novel postreplicative DNA modification. We also discuss perspectives on the physiological functions of the DNA phosphorothioate modification in bacteria and their implications.
Bacteria ; genetics ; metabolism ; DNA, Bacterial ; chemistry ; history ; metabolism ; Genes, Bacterial ; History, 20th Century ; History, 21st Century ; Multigene Family ; Streptomyces lividans ; genetics ; metabolism ; Sulfur ; chemistry ; history ; metabolism

The Lianhua Qingwen (LHQW) capsule is a popular traditional Chinese medicine for the treatment of viral respiratory diseases.In particular,it has been recently prescribed to treat infections caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).However,due to its complex composi-tion,little attention has been directed toward the analysis of chemical constituents present in the LHQW capsule.This study presents a reliable and comprehensive approach to characterizing the chemical constituents present in LHQW by high-performance liquid chromatography-Q Exactive-Orbitrap mass spectrometry (HPLC-Q Exactive-Orbitrap-MS) coupled with gas chromatography-mass spectrometry(GC-MS).An automated library alignment method with a high mass accuracy (within 5 ppm) was used for the rapid identification of compounds.A total of 104 compounds,consisting of alkaloids,flavonoids,phenols,phenolic acids,phenylpropanoids,quinones,terpenoids,and other phytochemicals,were suc-cessfully characterized.In addition,the fragmentation pathways and characteristic fragments of some representative compounds were elucidated.GC-MS analysis was conducted to characterize the volatile compounds present in LHQW.In total,17 compounds were putatively characterized by comparing the acquired data with that from the NIST library.The major constituent was menthol,and all the other compounds were terpenoids.This is the first comprehensive report on the identification of the major chemical constituents present in the LHQW capsule by HPLC-Q Exactive-Orbitrap-MS,coupled with GC-MS,and the results of this study can be used for the quality control and standardization of LHQW capsules.

Objective: To explore the prescription rules in treating liver cirrhosis's based on poison phlegm blood stasis and deficiency. Method: Clinical data of patients, who had been diagnosed with liver cirrhosis, was gathered. The data had been extracted, transformed and loaded through data integration and remittance, then, the data was analyzed by data classification, association, clustering and other large data analysis methods. Results: The prescription rules based on poison phlegm blood stasis and deficiency showed that according to medication frequency, detoxification drugs commonly used ArtemisiacapillarisThunb, Coptis chinensis Franch, Forsythia suspensa, Hedyotis diffusa Willd, and Scutellaria baicalensis Georgi, eliminating phlegm drugs commonly used Semen Coicis, Citrus aurantium L, Pinellia ternate, Pericarpium Citri Reticulatae and Trichosanthes kirilowii Maxim, removeing blood stasis drugs commonly used Radix Salviae Miltiorrhiae, Radix Curcumae, Rhizoma Curcumae, Herba Lycopi and Pollen Typhae, reinforcing deficiency drugs commonly used Poria, Carapax Trionycis, Rhizoma Atractylodis Macrocephalae, Radix Astragali seu Hedysari and Radix Codonopsis (Radix Pseudostellariae) . The selection of herbal medicine for poison in traditional Chinese medicine (TCM) is not only cold in property, bitter in flavor, but also converges to liver, gallbladder, spleen and stomach channel.The selection of herbal medicine for phlegm in TCM is not only warm in property, pungent in flavor, but also converges to spleen and lung channel. The selection of herbal medicine for blood stasis in TCM is not only cold in property, bitter in flavor, but also converges to liver, heart and spleen channel. The selection of herbal medicine for deficiency in TCM is not only mild in property, sweet in flavor, but also converges to spleen, liver and kidney channel. Conclusion: The syndrome differentiation and treatment of liver cirrhosis in Liver Institute of Hubei Provincial Hospital of Traditional Chinese are mainly based on poison phlegm blood stasis and deficiency.

Cardiac magnetic resonance (CMR) imaging provides accurate anatomic information and advanced soft contrast, making it the reference standard for assessing cardiac volumes and systolic function. In this review, we summarize the recent advances in CMR sequences. New technical development has widened the use of CMR imaging beyond the simple characterization of myocardial scars and assessment of contractility. These novel CMR sequences offer comprehensive assessments of coronary plaque characterization, myocardial fiber orientation, and even metabolic activity, and they can be readily applied in clinical settings. CMR imaging is able to provide new insights into understanding the pathophysiologic process of underlying cardiac disease, and it can help physicians choose the best treatment strategies. Although several limitations, including the high cost and time-consuming process, have limited the widespread clinical use of CMR imaging so far, recent advances in software and hardware technologies have made the future more promising.
Cardiac Volume ; Cardiology ; Cicatrix ; Heart Diseases ; Magnetic Resonance Imaging

Objective:To explore the influencing factors of uterine myometrial and parauterine venous plexus reflux during transvaginal four-dimensional contrast-enhanced hysterosalpingography, which will help reduce and avoid the occurrence of reflux and improve the accuracy of diagnosis.Methods:A total of 306 infertile patients who underwent transvaginal four-dimensional contrast-enhanced hysterosalpingograph from June 2016 to June 2017 in the Third Affiliated Hospital of Guangzhou Medical University were retrospectively enrolled. The ultrasonographic characteristics were reviewed and the correlations between reflux and endometrial thickness, days after menstruation, intrauterine operation history and patency of fallopian tube were analyzed.Results:The incidence of countercurrent during four-dimensional contrast-enhanced hysterosalpingography was 14.71%. The chi-square test showed that the endometrial thickness and the days after menstruation had statistically significant effects on the incidence of reflux ( P=0.031 and <0.001, respectively). There were no statistically significant effects of intrauterine operation history and patency of the fallopian tube on the incidence of reflux ( P=0.610, 0.137). Logistic regression analysis showed that the incidence of reflux was associated with endometrial thickness ( B=-1.171, P<0.001) and the days after menstruation ( B=0.439, P=0.015). Conclusions:Transvaginal ultrasound measurement of endometrial thickness before angiography and selection of appropriate examination time according to the menstrual cycle can effectively reduce the incidence of reflux, and adverse reactions, and improve the accuracy of four-dimensional contrast-enhanced hysterosalpingography.

Tunicamycin, a potent reversible translocase I inhibitor, is produced by several Actinomycetes species. The tunicamycin structure is highly unusual, and contains an 11-carbon dialdose sugar and an α, β-1″,11'-glycosidic linkage. Here we report the identification of a gene cluster essential for tunicamycin biosynthesis by high-throughput heterologous expression (HHE) strategy combined with a bioassay. Introduction of the genes into heterologous non-producing Streptomyces hosts results in production of tunicamycin by these strains, demonstrating the role of the genes for the biosynthesis of tunicamycins. Gene disruption experiments coupled with bioinformatic analysis revealed that the tunicamycin gene cluster is minimally composed of 12 genes (tunA-tunL). Amongst these is a putative radical SAM enzyme (Tun B) with a potentially unique role in biosynthetic carbon-carbon bond formation. Hence, a seven-step novel pathway is proposed for tunicamycin biosynthesis. Moreover, two gene clusters for the potential biosynthesis of tunicamycin-like antibiotics were also identified in Streptomyces clavuligerus ATCC 27064 and Actinosynnema mirums DSM 43827. These data provide clarification of the novel mechanisms for tunicamycin biosynthesis, and for the generation of new-designer tunicamycin analogs with selective/enhanced bioactivity via combinatorial biosynthesis strategies.
Actinobacteria ; enzymology ; genetics ; Base Sequence ; Biological Assay ; Carbohydrate Sequence ; Carbohydrates ; biosynthesis ; genetics ; Cloning, Molecular ; Gene Deletion ; Gene Library ; High-Throughput Screening Assays ; Molecular Sequence Data ; Multigene Family ; Recombinant Proteins ; biosynthesis ; genetics ; Sequence Analysis, DNA ; Streptomyces ; enzymology ; genetics ; Tunicamycin ; biosynthesis ; chemistry ; genetics

Cardiac magnetic resonance (CMR) imaging provides accurate anatomic information and advanced soft contrast, making it the reference standard for assessing cardiac volumes and systolic function. In this review, we summarize the recent advances in CMR sequences. New technical development has widened the use of CMR imaging beyond the simple characterization of myocardial scars and assessment of contractility. These novel CMR sequences offer comprehensive assessments of coronary plaque characterization, myocardial fiber orientation, and even metabolic activity, and they can be readily applied in clinical settings. CMR imaging is able to provide new insights into understanding the pathophysiologic process of underlying cardiac disease, and it can help physicians choose the best treatment strategies. Although several limitations, including the high cost and time-consuming process, have limited the widespread clinical use of CMR imaging so far, recent advances in software and hardware technologies have made the future more promising.

Human microbiome is comprised of symbiotic microorganisms in the human body, whose dynamic balance is closely related to human health, and is recognized as important "organs" that can regulate immunity, metabolism and other aspects in human body, and is associated with functions of many organs including lung, intestine, vagina and brain, becoming a potential target for the treatment of cancer, coronary heart disease, neurological diseases and other difficult diseases. In recent years, with the rapid development of microbiome sequencing and analysis technology, it has become an international focus and forefront to discover the relationship between human microorganisms and many diseases, as well as target for new treatment methods. Thus, we organized this special issue and publish reviews on study methodology, human disease and microbiome as well as therapeutic strategies, and provide important information to advance microbiome research in China.
China ; Humans ; Intestines ; Lung ; Microbiota ; Neoplasms