Melatonin regulates microglial polarization and protects against ischemic stroke-induced brain injury in mice.

Ischemic stroke is a leading cause of mortality and morbidity worldwide, with neuroinflammation playing a key role in its pathophysiology. Microglia, the primary immune cells in the brain, undergo rapid activation and phenotypic polarization, which are crucial for regulating neuroinflammatory responses following ischemic stroke. Melatonin is a promising neuroprotective agent that can regulate microglial polarization in central nervous system (CNS) diseases. However, the specific mechanism underlying the neuroprotective effects of melatonin against ischemic stroke-induced brain injury by modulating microglial polarization after ischemic stroke remains poorly understood. To investigate this mechanism, we used the transient middle cerebral artery occlusion/reperfusion (tMCAO/R) model in C57BL/6 mice to induce ischemic stroke and administered intraperitoneal melatonin (20 mg/kg) or an equivalent volume of vehicle daily after reperfusion. Our results demonstrated that melatonin treatment reduced the infarct volume, prevented neuronal loss and apoptosis, and improved neurological deficits after ischemic stroke. Furthermore, melatonin attenuated microglial activation and reactive astrogliosis, while promoting the polarization of microglia toward M2 phenotype via signal transducer and activator of transcription 1/6 (STAT1/6) pathways. Collectively, these findings suggest that melatonin exerts neuroprotective effects against ischemic stroke-induced brain injury by modulating microglial polarization toward M2 phenotype and has the potential as a promising candidate for the treatment of ischemic stroke.

Corrigendum: Molecular epidemiology and mechanism of Klebsiella pneumoniae resistance to ertapenem but not to other carbapenems in China.

[This corrects the article DOI: 10.3389/fmicb.2022.974990.].

Molecular epidemiology and mechanism of Klebsiella pneumoniae resistance to ertapenem but not to other carbapenems in China.

Resistance to only ertapenem is an unusual phenotype of carbapenem-resistant Klebsiella pneumoniae (CRKP). This study aimed to investigate the molecular epidemiology and underlying mechanism involved in ertapenem resistance of K. pneumoniae strains that are susceptible to meropenem and imipenem. Among the 697 K. pneumoniae strains isolated from 11 grade A hospitals in China, 245 were CRKP strains, of which 18 strains resistant only to ertapenem were isolated. The genotypes, phenotypes, drug resistance homology, and drug sensitivity were analyzed; moreover, the expressions of efflux pump components and outer membrane proteins were assessed. The whole genomes of these 18 strains were sequenced and analyzed for mutations leading to drug resistance. The results revealed that ertapenem resistance may be related to ramR mutation. The function of ramR was confirmed using gene complementation to the original strain to determine the mechanism underlying ertapenem resistance of K. pneumoniae strains. In total, 7.4% of the tested CRKP strains were resistant only to ertapenem. None of these strains contained carbapenemase genes. Of the 18 ertapenem-resistant strains, 17 expressed the efflux pump, and outer membrane protein expression was reduced or absent in 4 strains. Whole-genome sequencing revealed the presence of mutations that introduced premature ramR codons stop in 14 strains (77.78%). When a functional copy of ramR was restored in the 14 strains, the minimum inhibitory concentration of ertapenem decreased, inhibition of efflux pumps was not detected, and the expression of outer membrane protein OmpK35 was either increased or was restored. These findings reveal the existence of ertapenem-resistant K. pneumoniae exhibiting no clonal transmission between strains. Mutations in ramR were demonstrated to cause efflux pump inhibition and over-expression of outer membrane protein OmpK35 in some strains, which is implicated in ertapenem resistance only in K. pneumoniae.

Laser-Arc Hybrid Cladding of Al-Mg Alloy Coating on AZ80 Mg Alloy: Effect of Laser Beam Oscillations Amplitude.

The effect of beam oscillating amplitude on the microstructure and performance of AZ80 Mg alloy cladded with Al-Mg alloy coating by laser-arc hybrid welding was studied. The penetration depth decreases significantly while welds are widened because of the increase in the oscillating area of a laser beam. Alloy segregation and keyhole-induced porosity can be suppressed by the laser beam oscillation. With the increase in the oscillating amplitude, the Al distribution becomes uniform in the weld seam because of the rapid and fierce stirring by the oscillating laser. However, the diluting of the cladded Al alloy restrains the formation of the brittle Mg17Al12 phase, and then causes the weakening of hardness and wear resistance of the cladded layer. Considered comprehensively, the optimized oscillating amplitude was 1 mm, which can produce the weld seam with good appearance, fewer segregation and porosity defects, and acceptable hardness and wear resistance.

High-level ertapenem resistance in Klebsiella pneumoniae is due to RamA downregulation of ompK35 through micF.

An ertapenem-resistant Klebsiella pneumoniae clinical isolate (KP20) without carbapenemase and negative for the efflux pump inhibition test was resistant to ertapenem at a high level [minimum inhibitory concentration (MIC) = 64 mg/L] but susceptible to meropenem and imipenem. Second-generation sequencing was performed and a termination mutation was found in ramR. Complementation of ramR in KP20 reduced the ertapenem MIC by 128 times (from 64 mg/L to 0.5 mg/L). Overexpression of ramA and loss of OmpK35 were discovered in strain KP20 by quantitative reverse transcription PCR (RT-qPCR) and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), respectively. Furthermore, ramA deletion in strain KP20 resulted in a 128-fold decrease in the MIC of ertapenem (from 64 mg/L to 0.5 mg/L), and expression of OmpK35 was observed in KP20ΔramA by SDS-PAGE. Complementation of ramA in KP20ΔramA led to a 45.45-fold downregulation of ompK35. Complementation of ompK35 in KP20 could restore susceptibility to ertapenem (MIC reduced from 64 mg/L to 0.25 mg/L). Furthermore, results of the electrophoretic mobility shift assay showed that RamA could bind to the promoter of micF. These results showed that the termination mutation in ramR resulted in overexpression of ramA causing loss of OmpK35 expression through upregulation of micF, revealing the mechanism of ertapenem resistance only in K. pneumoniae.

Diagnosis and treatment of an elderly patient with 2019-nCoV pneumonia and acute exacerbation of chronic obstructive pulmonary disease in Gansu Province: A case report.

BACKGROUND: In December 2019, the first patient with 2019-novel coronavirus (2019-nCoV) was reported in Wuhan, China, and the disease spread rapidly across the country and surrounding countries within 2 mo. As of February 29, 2020, a total of 91 confirmed cases had been reported in Gansu Province. This case report of the diagnosis and treatment of an elderly patient with 2019-nCoV pneumonia complicated by acute exacerbation of chronic obstructive pulmonary disease in Gansu Province aims to provide a better reference for the treatment of patients in the future. CASE SUMMARY: The patient, a 94-year-old female, lived in Maiji District of Tianshui, Gansu Province, China. On January 30, 2020, she was admitted to the Fourth People's Hospital of Tianshui after 9 d of close contact with a patient with 2019-nCoV pneumonia. She was subsequently admitted to Gansu Provincial Hospital of Traditional Chinese Medicine for isolation and transferred to Tianshui Gansu Provincial Hospital of Infectious Diseases on February 3, 2020 for treatment. Upon initial examination, her body temperature was 36.7 °C , pulse was 80, breathing was 20, and blood pressure was 130/80 mmHg. She was conscious with normal development and normal nutrition. The pharynx was not red, and bilateral tonsils were not red and swollen. The lungs sounded slightly coarse with no dry or wet rales. The first symptoms were cough and fatigue on 2 February. The patient was hospitalized for 12 d. After active treatment, she was discharged on February 14 with a good prognosis. CONCLUSION: A history of exposure to the affected area or patient is a major cause of 2019-nCoV infection, and population clustering is a high risk factor for transmission. Patients may not necessarily have respiratory system symptoms as the only clinical manifestation but may also have concomitant or first onset digestive symptoms. Attention should be paid to the prevention and treatment of multiple organ dysfunction syndrome. Nucleic acid testing is extremely important and needs to be repeated several times. Laboratory and auxiliary examination indicators during the first week of admission are extremely important. It is feasible to carry out dynamic and continuous index monitoring, which can predict and guide the prevention and treatment of multiple organ dysfunction and the prognosis of the disease.

[Visualized analysis of literature on sepsis caused by Gram positive bacteria in SinoMed].

OBJECTIVE: To understand the current situation of research in the field of sepsis caused by Gram positive bacteria (G+ bacteria) in China, to clarify the research content and analyze its general research direction, so as to find the hot topics of research in recent years. METHODS: The literatures in SinoMed related to sepsis caused by G+ bacteria and published in Chinese from building database to October 2019 were screened. The distribution and trend of the published year, journals, research institutions and researchers of relevant literature were analyzed, and Ucinet 6.0 software was used to draw the social network graph of the researchers and to analyze their internal relations. The subject words of related literatures were extracted. The relationship among the subject words in related literatures was arranged according to the centrality by NetDraw in Ucinet 6.0 software, the bibliographic information co-occurrence analysis system software (BICOMS2 software) was used to classify the subject words and the visualization matrix was generated. The graph clustering tool software (gCLUTO software) was used to cluster the subject words, and the visualization surface graph was generated to analyze the current research hot spot, research trend and research direction of G+ bacteria-induced sepsis. RESULTS: A total of 1 976 literatures about sepsis caused by G+ bacteria were retrieved, and 26 literatures in conference summaries, news reports, research information, missing content, or inconsistent with the theme were excluded. Finally, a total of 1 950 literatures were enrolled in final analysis. The number of published literatures analysis showed that from 1979 to 1992, there were few studies about sepsis caused by G+ bacteria, which increased geometrically from 2008, and the number of literatures published from 2008 to 2018 was 1 144, accounting for 58.67% (1 144/1 950). From 1979 to 2019, 23 high-yield institutions published more than 5 literatures, of which 6 were institutions with 10 or more literatures, and only one institution with more than 20 literatures. There were only 5 journals with more than 100 articles, 5 381 authors involved in the literatures, but few authors with more than 10 literatures published, and no inter-provincial or inter-municipal cooperation was found. A social network analysis of 103 high-frequency subject words that appeared more than 5 times showed that the study of sepsis caused by G+ bacteria mainly focused on "sepsis", including the incidence of sepsis caused by drug resistant Staphylococcus aureus was on the rise, especially in newborns and children with weakened immune systems, the selection of therapeutic drugs gradually developed to glycopeptides with strong anti-drug resistance and synthetic oxazolidinones. The research and development of drugs for the treatment of sepsis caused by G+ bacteria might become a new research direction or field in the future. Cluster analysis of 103 high-frequency subject words showed that the research hot spots of G+ bacteria-induced sepsis mainly focused on five topics, namely early diagnosis of sepsis; bacterial infection pathway of sepsis, nosocomial infection and bacterial drug resistance; the basis of epidemiological prevention and treatment of sepsis; venous catheter infection-related sepsis; the treatment, nursing and prognosis of patients with sepsis. CONCLUSIONS: The studies of sepsis caused by G+ bacteria are winning more and more attention, but the resources sharing and academic exchanges among hospitals need to be further improved.

The effect of taste and taste perception on satiation/satiety: a review.

As the prevalence of being overweight and obesity has increased worldwide, there is an increasing concern about satiation/satiety that can be achieved by eating. The ability of an individual to perceive tastes in the mouth is believed to be one of the many factors that influence food intake; the taste may affect appetite regulation and energy intake, playing an important role in promoting satiation/satiety. Satiation/satiety is actually induced by food and may be related to physiological and psychological factors such as several basic tastes, the exposure time of the taste and the cognition of different groups and individuals. This paper reviews the mechanism by which taste regulates satiation/satiety and demonstrates how taste and the taste perception of food prompt the brain to send satiation/satiety signals. Existing problems in taste and satiation/satiety and the prospective application of related research in the food industry are addressed, providing a scientific basis and theoretical guidance for the development and utilization of satiation/satiety from the perspective of taste.

Overexpressed circPVT1 in oral squamous cell carcinoma promotes proliferation by serving as a miRNA sponge.

Circular RNAs (circRNAs) comprise a novel class of widespread non­coding RNAs that may regulate gene expression in eukaryotes. However, the characterization and function of circRNAs remain elusive in human cancer, including oral squamous cell carcinoma (OSCC). In this study, the expression level of circPVT1 in OSCC was detected and define its functional role in initiation and progression of OSCC. It was identified that circPVT1 was upregulated in OSCC cells and specimens. Knockdown of circPVT1 suppressed cell proliferation as evidenced by Cell Counting kit­8 assay and elevated Ki­67 expression. Mechanistically, it was demonstrated that circPVT1 possessed two targeting sites of microRNA (miRNA/miR)­125b and could effectively sponge miR­125b to release its downstream mRNA targets. Subsequently, the downstream target signal transducer and activator of transcription 3 (STAT3) was verified as a direct target of miR­125b and STAT3 expression was regulated by the circPVT1/miR­125b axis. CircPVT1 functioned as competing endogenous RNA (ceRNA) to increase the STAT3 level and cell proliferation through sponging miR­125b. In conclusion, circPVT1 regulates cell proliferation and may serve as a promising therapeutic target for OSCC patients. Therefore, silencing of circPVT1 could be a future direction to develop a novel treatment strategy.

[Visualization studies on research status of the ventilator-associated pneumonia based on SinoMed database].

OBJECTIVE: To survey the distribution pattern and subject domain knowledge of the literatures about ventilator-associated pneumonia (VAP). METHODS: Literatures about VAP published until December 2017 were identified in SinoMed database for statistics and analysis. The information of author, organization and province was extracted by BICOMS software for generating co-occurrence matrix, at the same time, the topic words were cluster analyzed by Gcluto software to generate topical visual surface maps and visualization matrices, and the current research hotspots were analyzed. NetDraw from Ucinet 6.0 software was used to arrange the relationship among topic words according to the centrality, and the social network diagrams of authors, authors' provinces and institutions were draw to analyze the current status of VAP research cooperation. RESULTS: 4 851 VAP-related literatures were retrieved preliminarily, and 43 were excluded from abstracts, news reports, information and missing literatures. Finally, a total of 4 808 articles were enrolled in the visual analysis. From 2001 to 2004, the number of VAP-related literatures published was less than 10. Since 2009, the number of VAP documents had increased steadily, from 2010 to 2017, the peak period of publications reached 91.7% (4 411/4 808). According to the analysis of the amount of publications, the top three of 34 provincial administrative regions that published VAP-related literature in China were Guangdong Province (n = 628), Jiangsu Province (n = 478) and Zhejiang Province (n = 404), the number of hospitals issued by the First Affiliated Hospital of Chongqing Medical University was the largest (n = 20); there was only one journal with more than 100 articles, and there were 154 journals with only one article, accounting for 34.8% of the total number of journals. A total of 9 921 authors participated in the VAP-related literature writing, the number of high-yielding authors was not large, and the institution could not establish an effective social network diagram, suggesting that communication and cooperation should be strengthened in hospitals and outside hospitals. The results of the topic words social network analysis showed that the VAP research field was centered around the core of "mechanical ventilation", "intensive care unit (ICU)", "risk factor analysis", "nursing", "etiological analysis", "preventive measures" and "pathogens". The current research hotspots were at the edge of the network map, such as "drug sensitivity analysis", "Acinetobacter baumannii", "bronohoalveolar lavage (BAL)" and "acute exacerbation of chronic obstructive pulmonary disease (AECOPD)". By clustering 80 high-frequency topic words, at present, VAP research hotspots were mainly focus on five topics: obstructive pulmonary disease, especially in acute exacerbation, was prone to VAP; concerned about newborns and children's VAP; types, drug resistance and selection of antimicrobial agents for VAP pathogens in ICU; clinical efficacy and prognosis of VAP through preventive measures, pulmonary supportive care and comprehensive care interventions; oral care and airway management during mechanical ventilation was also the key aspect of the treatment of VAP. CONCLUSIONS: In recent years, the academics had attached great importance to the study of VAP, the number of publications had reached a historical peak, and the research direction was diverse. However, it was necessary to strengthen cooperation among research institutes, collect and count epidemiological data, improve and expand the research quality and scale of clinical diagnosis, nurse, prevention, pathogen distribution and drug resistance analysis.