PHT427 as an effective New Delhi metallo-ß-lactamase-1 (NDM-1) inhibitor restored the susceptibility of meropenem against Enterobacteriaceae producing NDM-1.

Introduction: With the increasingly serious problem of bacterial drug resistance caused by NDM-1, it is an important strategy to find effective inhibitors to assist ß-lactam antibiotic treatment against NDM-1 resistant bacteria. In this study, PHT427 (4-dodecyl-N-1,3,4-thiadiazol-2-yl-benzenesulfonamide) was identified as a novel NDM-1 inhibitor and restored the susceptibility of meropenem against Enterobacteriaceae producing NDM-1. Methods: We used a high throughput screening model to find NDM-1 inhibitor in the library of small molecular compounds. The interaction between the hit compound PHT427 and NDM-1 was analyzed by fluorescence quenching, surface plasmon resonance (SPR) assay, and molecular docking analysis. The efficacy of the compound in combination with meropenem was evaluated by determining the FICIs of Escherichia coli BL21(DE3)/pET30a(+)-bla NDM-1 and Klebsiella pneumoniae clinical strain C1928 (producing NDM-1). In addition, the mechanism of the inhibitory effect of PHT427 on NDM-1 was studied by site mutation, SPR, and zinc supplementation assays. Results: PHT427 was identified as an inhibitor of NDM-1. It could significantly inhibit the activity of NDM-1 with an IC50 of 1.42 µmol/L, and restored the susceptibility of meropenem against E. coli BL21(DE3)/pET30a(+)-bla NDM-1 and K. pneumoniae clinical strain C1928 (producing NDM-1) in vitro. The mechanism study indicated that PHT427 could act on the zinc ions at the active site of NDM-1 and the catalytic key amino acid residues simultaneously. The mutation of Asn220 and Gln123 abolished the affinity of NDM-1 by PHT427 via SPR assay. Discussion: This is the first report that PHT427 is a promising lead compound against carbapenem-resistant bacteria and it merits chemical optimization for drug development.

Correlation Between Aggressive Behavior and Impulsive and Aggressive Personality Traits in Stable Patients with Schizophrenia.

Purpose: To explore the correlation between aggressive behavior and impulsive and aggressive personality traits in inpatients with schizophrenia. Methods: In total, 367 inpatients with schizophrenia were divided into two groups: the aggressive group and the non-aggressive group. We assessed inpatients' psychotic symptoms as well as their aggressive and impulsive personality traits using the Positive and Negative Symptom Scale, the Barratt Impulsiveness Scale, and the Buss-Perry Aggression Questionnaire. Results: Compared with the scores of inpatients in the non-aggressive group, the total Buss-Perry Aggression Questionnaire, subscale, and Barratt Impulsiveness Scale behavioral factor scores in those in the aggressive group were higher (p < 0.05). The results of logistic regression analysis suggested that a high Positive and Negative Symptom Scale positive factor score (odds ratio = 1.07) and a high Buss-Perry Aggression Questionnaire physical aggression score (odds ratio = 1.02) were risk factors for aggressive behavior. Conclusion: Hospitalized patients with schizophrenia with more severe positive symptoms and aggressive traits may be more prone to aggressive behavior.

Protective effect and mechanism of baicalin on lung inflammatory injury in BALB/cJ mice induced by PM2.5.

The public health harms caused by fine particulate matter (PM2.5) have become a global focus, with PM2.5 exposure recognized as a critical risk factor for global morbidity and mortality. Chronic inflammation is the common pathophysiological feature of respiratory diseases induced by PM2.5 and is the most critical cause of all these diseases. However, presently there is a lack of effective preventive and therapeutic approaches for inflammatory lung injuries caused by PM2.5 exposure. Baicalin is a herb-derived effective flavonoid compound with multiple health benefits. This study established a murine lung inflammatory injury model via inhalation of PM2.5 aerosols. The data showed that after baicalin intervention, lung injury pathological score of baicalin (4.16 ± 0.54, 3.33 ± 0.76, 4.00 ± 0.45) and claricid (3.00 ± 0.78) treatments were markedly lower than PM2.5-treated mice (6.17 ± 0.31), and pathological damage was alleviated. Compared to the PM2.5 group, the spleen and lung indexes in the baicalin and claricid groups were significantly reduced. The inflammatory cytokines of TNF-α, IL-18, and IL-1ß in serum, alveolar lavage fluid, and lung tissue were significantly decreased in the baicalin and claricid groups. The expressions of inflammatory pathway-related genes and proteins HMGB1, NLRP3, ASC, and caspase-1 were up-regulated in the PM2.5 group. The expressions of these genes and proteins were significantly decreased following baicalin treatment. The lung function indicators showed that the MV (65.94 ± 8.19 mL), sRaw (1.79 ± 0.08 cm H2O.s), and FRC (0.52 ± 0.01 mL) in the PM2.5 group were higher than in the control and baicalin groups, and respiratory function was improved by baicalin. PM2.5 exposure markedly altered the bacterial composition at the genus level. The dominant flora relative abundances of uncultured_bacterium_f_Muribaculaceae, Streptococcus, and Lactobacillus, were decreased from the control group (9.20%, 8.53%, 6.21%) to PM2.5 group (6.26%, 5.49%, 4.77%), respectively. Following baicalin intervention, the relative abundances were 9.72%, 6.65%, and 3.57%, respectively. Therefore, baicalin could potentially prevent and improve mice lung inflammatory injury induced by PM2.5 exposure. Baicalin might provide a protective role by balancing oropharyngeal microbiota and affecting the expression of the HMGB1/Caspase1 pathway.

Integrated Medical Care and the Continuous 4C Nursing Model to Improve Nursing Quality and Clinical Treatment of Patients with Acute Stroke: Based on a Retrospective Case-Control Study.

Objective: This research paper is based on a retrospective case-control study for exploring the effects of medical nursing integration and the continuous 4C nursing model to improve the clinical treatment and nursing quality of patients with acute stroke. Method: For this purpose, a total of 313 patients with acute stroke, treated in our hospital from February 2020 to April 2021, were enrolled. They were divided into control and study groups with an even number of patients. The control group received integrated medical care number (N = 156), while the study group received integrated medical care and a continuous 4C nursing model (N = 157). In integrated medical care, the general data, self-nursing ability, degree of neurological impairment, Fugl-Meyer Assessment (FMA) score, Barthel index score, and quality of life score were compared between the two groups. Result: The self-nursing concept, self-nursing responsibility, self-nursing skills, health knowledge, and total score of the patients in the study group were higher than those in the control group (P < 0.05). The neurological function scores of the study group were lower than those of the control group at 1, 3, and 6 months after discharge (P < 0.05). The scores of the study group were higher than those of the control group at 1, 3, and 6 months after discharge (P < 0.05). The Barthel index score of the study group was higher than that of the control group at 1, 3, and 6 months after discharge. The scores of physical function, psychological function, social function, and health self-cognition in the study group were lower than those in the control group (P < 0.05). Conclusion: The application of integrated medical care and the continuous 4C nursing model for patients with acute stroke is beneficial to enhance the degree of neurological impairment of stroke patients, improve activities of daily life and motor function, and facilitate patients' quality of life. It is helpful to strengthen the attitude and feeling of cooperation between doctors and nurses, promote cooperation between doctors and nurses, reduce the defects of nursing work, heighten the quality of nursing, and achieve the requirement and goal of effectively promoting high-quality nursing.

Risk Factors and Risk Model Construction of Stroke in Patients with Vertigo in Emergency Department.

Objective: We aimed to explore the risk factors of stroke in patients with vertigo in the emergency department and establish a risk prediction model for stroke patients. Methods: A total of 301 patients experiencing vertigo in our hospital from January 2020 to January 2021 were retrospectively included. Patients were divided into the stroke group (n = 56) and the nonstroke group (n = 245). The clinical characteristics of patients in both groups were collected and compared, followed by binary logistic regression that was employed to determine the risk factors that affect stroke diagnosis. The receiver operating characteristic (ROC) curve was used to clarify the effectiveness of the constructed model. Results: Patients in the stroke group were older and had higher systolic and diastolic blood pressure on admission than the nonstroke group. Meanwhile, they demonstrated a higher proportion of diabetes and atrial fibrillation and focal muscle weakness, dysarthria, dysphagia, or ataxia in neurological examinations compared to the nonstroke group (all P < 0.05). The proportion of patients in the nonstroke group who had a history of vertigo or inner ear disease was significantly higher than that in the stroke group (P < 0.05). The patient's age ≥ 60 years old (OR = 3.57), diabetes (OR = 4.57), atrial fibrillation (OR = 4.26), previous history of vertigo or inner ear disease (OR = 0.16), focal muscle weakness (OR = 4.34), and dysphagia or ataxia (OR = 4.08) were associated with a higher risk of stroke. The area under the curve for stroke was 0.87, and the sensitivity and specificity were 98.2% and 57.6%, respectively, as the sum of the assigned scores was greater than 3. Conclusions: Age ≥ 60 years old, diabetes, atrial fibrillation, previous history of vertigo or inner ear disease, focal muscle weakness, dysphagia, or ataxia were associated with a higher risk of stroke. The risk model constructed based on our findings may help to assess the risk of stroke in patients with vertigo in the emergency department.

IMB-XMA0038, a new inhibitor targeting aspartate-semialdehyde dehydrogenase of Mycobacterium tuberculosis.

The emergence of drug-resistant tuberculosis (TB) constitutes a major challenge to TB control programmes. There is an urgent need to develop effective anti-TB drugs with novel mechanisms of action. Aspartate-semialdehyde dehydrogenase (ASADH) is the second enzyme in the aspartate metabolic pathway. The absence of the pathway in humans and the absolute requirement of aspartate in bacteria make ASADH a highly attractive drug target. In this study, we used ASADH coupled with Escherichia coli type III aspartate kinase (LysC) to establish a high-throughput screening method to find new anti-TB inhibitors. IMB-XMA0038 was identified as an inhibitor of MtASADH with an IC50 value of 0.59 µg/mL through screening. The interaction between IMB-XMA0038 and MtASADH was confirmed by surface plasmon resonance (SPR) assay and molecular docking analysis. Furthermore, IMB-XMA0038 was found to inhibit various drug-resistant MTB strains potently with minimal inhibitory concentrations (MICs) of 0.25-0.5 µg/mL. The conditional mutant strain MTB::asadh cultured with different concentrations of inducer (10-5 or 10-1 µg/mL pristinamycin) resulted in a maximal 16 times difference in MICs. At the same time, IMB-XMA0038 showed low cytotoxicity in vitro and vivo. In mouse model, it encouragingly declined the MTB colony forming units (CFU) in lung by 1.67 log10 dosed at 25 mg/kg for 15 days. In conclusion, our data demonstrate that IMB-XMA0038 is a promising lead compound against drug-resistant tuberculosis.

Isosinensetin alleviates the injury of human bronchial epithelial cells induced by PM2.5.

Flavonoids which are extracted from citrus peel and pulp have been reported to have multiple beneficial effects on human health. Isosinensetin (ISO) is a type of flavonoid compound, which has several protective effects including anticancer, antioxidant, antiviral, anti-inflammatory and bacteriostatic. However, the molecular mechanism of its antioxidant and anti-inflammatory effects remain unclear. The present study aimed to investigate the intervention effect and possible mechanism of ISO on human bronchial epithelial cells injured by fine particular matter ≤2.5 µm in diameter (PM2.5). In the present study, the cell viability was detected by Cell Counting Kit-8 method. The levels of pro-inflammatory cytokines were analyzed by ELISA. The level of reactive oxygen species (ROS) was detected by fluorescence probe. The expression levels of proliferating cell nuclear antigen (PCNA), nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor ÐºΒ (NF-кB) proteins were detected by western blotting. The results revealed that ISO evidently increased the viability of 16-HBE cells and sharply decreased the levels of pro-inflammatory factors in cell culture supernatant. ISO significantly inhibited ROS release caused by PM2.5. Moreover, the expression levels of PCNA, Nrf2 and NF-кB proteins were downregulated after ISO incubation. These results indicated that ISO alleviated 16-HBE-cell injury by PM2.5 through the ROS-Nrf2/NF-кB signaling pathway.

Streptococcus shenyangsis sp. nov., a New Species Isolated from the Oropharynx of a Healthy Child from Shenyang China.

A Gram-positive, catalase-negative, coccus-shaped, chain-forming organism isolated from the oropharynx of a healthy child in Shenyang, China, was subjected to phenotypic and molecular taxonomic analyses. 16S rRNA sequence analysis indicated that this bacterium represents a new member of the genus Streptococcus and is closely related to Streptococcus oralis subsp. dentisani DSM 27088. According to DNA-DNA hybridization analysis, strain D19T was less than 70% similar to other strains with close genetic relationships. Fatty acid analysis, physiological, and biochemical tests showed that strain D19T was different from the published Streptococcus species. The genome of strain D19T is 2,023,003 bp long with a GC content of 39.9 mol%. It contains 1889 protein-coding genes and 50 RNA genes. These results show that Streptococcus shenyangsis sp. nov. strain D19T is a new species.

Impaired Emotional Self-Referential Processing in First-Episode Schizophrenia.

Impairments in self-representation are relevant to the expression of psychosis. To date, the characteristics and neural mechanisms of self-impairment in schizophrenia remain unclear. To this end, we used event-related potentials (ERPs) to measure brain activity in 56 first-episode patients with schizophrenia and 56 healthy controls. Participants judged personal trait adjectives regarding themselves, their mothers, or a public person, followed by an unexpected old/new recognition test. The recognition score for mother-reference adjectives was lower than that for self-reference adjectives in patients, while the control group showed comparatively high recognition scores for both self- and mother-referential adjectives. In addition, control subjects recognized more negative words, while patients remembered more positive words. ERP data revealed that controls exhibited typical task effects (self-reference = mother-reference > other-reference) during both automatic attention and effortful encoding periods [indexed by P2 and the late positive potential (LPP), respectively]. In contrast, patients only exhibited the task effect in the P2 amplitude. Moreover, controls exhibited larger P2 amplitudes during encoding negative than positive words, whereas patients had enhanced LPP amplitudes during memory retrieval of positive compared to negative words. These findings demonstrated self-representation dysfunction in first-episode schizophrenic patients in mother (the intimate other) referential processing and the absence of a negative memory bias.

Lentinan Attenuated the PM2.5 Exposure-Induced Inflammatory Response, Epithelial-Mesenchymal Transition and Migration by Inhibiting the PVT1/miR-199a-5p/caveolin1 Pathway in Lung Cancer.

PM2.5 plays an important role in the physiological and pathological progression of lung cancer. Lentinan exerts antitumor activity in many kinds of human cancers. Plasmacytoma variant translocation 1 (PVT1) exerts antitumor activity in many kinds of human cancers. However, the role and underlying molecular mechanism of PVT1 in the role of lentinan in PM2.5-exposed lung cancer are still largely unknown. Our study confirmed that PM2.5 exposure induced the production of inflammatory factors, epithelial-mesenchymal transition (EMT) and migration of lung cancer cells. Lentinan exerted antitumor effects by inhibiting the production of inflammatory factors, EMT, and migration of lung cancer cells. Lentinan suppressed PM2.5 exposure-induced cellular progression by inhibiting the PM2.5 exposure-induced elevation of PVT1 expression. PVT1 absorbed miR-199a, and miR-199a inhibited caveolin1 expression and thus formed the PVT1/miR-199a/caveolin1 signaling pathway in lung cancer cells. Our study revealed that silencing of the PVT1/miR-199a/caveolin1 signaling pathway affected the role of lentinan in PM2.5-exposed lung cancer cells. Thus, this study first investigated the role of lentinan in PM2.5-exposed lung cancer cells and further displayed the underlying molecular mechanism, providing a potential treatment for PM2.5-exposed lung cancer.

Description and genomic characterization of Streptococcus symci sp. nov., isolated from a child's oropharynx.

Using the culturomics approach, we isolated a new Streptococcus species, strain C17T, from the oropharynx mucosa sample of a healthy 5-year-old child living in Shenyang, China. We studied the phenotypic, phylogenetic, and genomic characteristics of strain C17T, which was identified as a Gram-positive, coccus-shaped, non-motile, aerobic, catalase-negative bacteria. Its growth temperatures ranged from 20 to 42 °C, with optimal growth at 37 °C. Acid production could be inhibited by two sugars, trehalose and raffinose. In C17T, the reactions for enzyme lipase (C14) were confirmed to be negative, whereas those for alkaline phosphatase, α-glucosidase, and hippuric acid hydrolysis were positive. The C17T genome contained 2,189,419 base pairs (bp), with an average G+C content of 39.95%, encoding 2092 genes in total. The 16S ribosomal RNA sequence showed 99.8% similarity with the newly identified Streptococcus pseudopneumoniae ATCC BAA-960T. The main fatty acid components in C17T were C16:0, C18:1 w7c, C18:0, and C18:1 w9c, all of which can be found in other species of the Streptococcus genus. Strain C17T showed high susceptibility to clindamycin, linezolid, vancomycin, chloramphenicol, and cefepime, and moderate susceptibility to erythromycin. The obtained dDDH value between strain C17T and the closest species was 52.9%. In addition, the whole genome sequence of strain C17T had an 82.21-93.40% average nucleotide identity (ANI) with those strains of closely related Streptococcus species, indicating that the strain C17T was unique among all Streptococcus species. Based on these characteristics, we determine that C17T is a novel species, named Streptococcus symci sp. nov. (= GDMCC 1.1633 = JCM 33582).

The Impact of Air Pollution on Hospitalization for Cardiovascular and Cerebrovascular Disease in Shenyang, China.

BACKGROUND: The aim of this study was to investigate the overall impact of PM2.5, PM10, NO2, SO2, CO, and O3 on the admission of cardiovascular and cerebrovascular disease. METHODS: We collected data on cardiovascular and cerebrovascular disease admissions from two hospitals in Shenyang Liaoning, China from Jan 2014 to Dec 2017, as well as daily measurements of six pollutants at 11 sites in Shenyang. The generalized additive model was used to assess the association between daily contaminants and admission to cardiovascular and cerebrovascular disease. RESULTS: The single-contamination model showed a significant correlation between NO2, O3, PM10 and cardiovascular and cerebrovascular diseases at lag0 day. Air pollutants had lag effects on different gender groups. Excess relative risks (ERs) associated with a 10 µg/m3 increase were 1.522(1.057, 1.988) on lag02 for NO2, 0.547% (0.367%, 0.728%), 0.133% (0.061%, 0.205%) on lag3 for O3 and PM10. The dual pollutant model showed that the effects of NO2, O3, and PM10 after adjusting the influence of other pollutants were still statistically significant. CONCLUSION: Short-term exposure to ambient air pollution (NO2, O3, and PM10) may be associated with an increased risk of daily cardiovascular and cerebrovascular admission, which may provide reliable evidence for further understanding of the potential adverse effects of air pollution on cardiovascular and cerebrovascular diseases.

Systematic research of H2dedpa derivatives as potent inhibitors of New Delhi Metallo-ß-lactamase-1.

New Delhi Metallo-ß-lactamase-1 (NDM-1), a Zn (II)-dependent enzyme, can catalyze the hydrolysis of almost all ß-lactam antibiotics including carbapenems, resulting in bacterial antibiotic resistance, which threatens public health globally. Based on our finding that H2dedpa is as an efficient NDM-1 inhibitor, a series of H2dedpa derivatives was systematically prepared. These compounds exhibited significant activity against NDM-1, with IC50 values 0.06-0.94 µM. In vitro, compounds 6k and 6n could restore the activity of meropenem against Klebsiella pneumoniae, Escherichia coli and Proteus mirabilis possessing either NDM or IMP. In particular, the activity of meropenem against E. coli producing NDM-4 could be improved up to 5333 times when these two compounds were used. Time-kill cell-based assays showed that 99.9% of P. mirabilis were killed when treated with meropenem in combination with compound 6k or 6n. Furthermore, compounds 6k and 6n were nonhemolytic (HC50 > 1280 µg/mL) and showed low toxicity toward mammalian (HeLa) cells. Mechanistic studies indicated that compounds 6k and 6n inhibit NDM-1 by chelating the Zn2+ ion of the enzyme.

Structural Revision and Absolute Configuration of Burnettramic Acid A.

The recently discovered antibiotic burnettramic acid A (1) and three new congeners, burnettramic acids C-E (2-4), were identified from the co-cultures of two marine Aspergillus strains. The structure of burnettramic acid A was revised on the basis of reinterpretation of the nuclear magnetic resonance (NMR) data and chemical derivatization. The full absolute configurations of burnettramic acids were established using the Mosher ester method and Marfey's analysis, combined with density functional theory calculation of NMR and electric circular dichroism data.

A quencher-free 2-aminopurine modified hairpin aptasensor for ultrasensitive detection of Ochratoxin A.

A sensitive, efficient and quencher-free fluorescence aptasensor to detect Ochratoxin A (OTA) based on aptamer, 2-aminopurine (2AP) labeled Oligonucleotide sequence, as well as exonuclease I (Exo I) activity was developed. In which the aptamer specific to OTA was modified into a hairpin structure, and 8 bases at the 3' ends are exposed (H); also, 2AP is embedded in the oligonucleotide complementary to the 8 bases (2AP-probe).The detection principle based on 2AP-probe could be bonded to its complementary sequence and quenches the fluorescence of 2AP; The aptamer has a stronger affinity for the target than its complementary sequence; Exo I can dissociate single-stranded DNA and has little effect on double-stranded DNA as well as folded DNA. In the absence of OTA, the fluorescence of 2AP is quenched due to the complementary pairing of H and 2AP-probe; in the presence of OTA, H selective binding target is detached from 2AP-probe, and the fluorescence of 2AP is slightly restored. Moreover, when the Exo I is added to the detection system, 2AP-probe is dissociated by the Exo I to release the free 2AP, and the fluorescence of the system is further enhanced thereby realizing the detection of OTA. The detection limit of the aptasensor was low as 0.03 nM with a linear range of 0.5-100 nM. Moreover, the aptasensor has good selectivity and practicability and also has good potential in realizing the detection of toxic and harmful substances in food complex matrices.

Screening of antagonistic strains of respiratory origin and analysis of their bacteriostatic effects on pathogens.

OBJECTIVE: To find antagonistic strains in the respiratory tract having bacteriostatic properties against common pathogens. METHODS: The oropharyngeal microbiota of five healthy children aged 4-6 years were collected and α-hemolytic bacteria screened on 15% sheep blood agar. Bacteriostatic effects of the isolated α-hemolytic bacteria on Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Streptococcus pyogenes were evaluated by the Oxford cup method. Antagonistic strains were identified by mass spectrometry, and the16S rDNAs were sequenced, and their best bacteriostatic concentrations and antagonistic spectra for Klebsiella pneumoniae, Proteus vulgaris, Enterobacter cloacae, Acinetobacter Baumanii, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Streptococcus pyogenes were evaluated. RESULTS: Of 300 isolated α-hemolytic bacterial clones, four exhibited bacteriostatic activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Streptococcus pyogenes. Mass spectrometric analyses revealed that two of them were Streptococcus mitis and two others were Streptococcus parasanguinis strains. Further tests showed that all 4 antagonistic strains also had bacteriostatic effects on Klebsiella pneumoniae, Proteus vulgaris, Enterobacter cloacae, and Acinetobacter Baumanii, and the mode of action was not mediated by lactic acid production. CONCLUSION: Four antagonistic Streptococcus strains derived from oropharyngeal microbiotas showed bacteriostatic effects on pathogens and may be involved in pharyngeal microbiome homeostasis.

Exposure to atmospheric pollutants is associated with alterations of gut microbiota in spontaneously hypertensive rats.

Atmospheric particulate matter with a diameter <2.5 µm (PM2.5) and pollution are worldwide environmental problems and may have negative effects on cardiovascular disease through the lung and gut. The dynamics of intestinal microflora in response to particulate pollutants is unclear. The present study investigated changes in the gut microbiota related to pollutant exposure using spontaneously hypertensive rats (SHR). DNA was extracted from fecal samples. Amplicon Generation and the quality control of PCR products were performed. PCR products was sequenced on an Illumina HiSeq 2500 platform. Data analysis included: operational taxonomic unit (OTU) clustering and species annotation, alpha diversity, beta diversity, principal coordinates analysis (PCoA), and the use of PICRUSt bioinformatics software. The microbial diversity of the SHR rats was inversely associated with exposure to pollutants. In terms of relative abundance, 24 bacterial genera and 2 genera in particular (Actinobacillus and Fusobacterium) significantly declined, and one genus (Treponema) increased. Moreover, pollutant exposure was associated with the accumulation of genes from the gut microbiota that are implicated in cardiovascular diseases. From the long-term exposure experiment, rats appeared to respond to pollutant injury. In conclusion, these results suggest that the effects of atmospheric pollutants on organisms are not limited to the respiratory tract, but also include the gastrointestinal tract. Pollutants are likely to influence the intestinal microbiota and promote the progression of cardiovascular disease.

Broad-Spectrum Antiviral Natural Products from the Marine-Derived Penicillium sp. IMB17-046.

A new pyrazine derivative, trypilepyrazinol (1), a new α-pyrone polyketide, (+)-neocitreoviridin (2), and a new ergostane analogue, 3ß-hydroxyergosta-8,14,24(28)-trien-7-one (3), were isolated and characterized along with five known compounds from the marine-derived fungus Penicillium sp. IMB17-046. The structures of these new compounds were determined using spectroscopic data analyses (HRESIMS, 1D- and 2D-NMR), X-ray crystallography analysis, and TDDFT ECD calculation. Compounds 1 and 3 exhibited broad-spectrum antiviral activities against different types of viruses, including human immunodeficiency virus (HIV), hepatitis C virus (HCV), and influenza A virus (IAV), with IC50 values ranging from 0.5 to 7.7 µM. Compounds 1 and 2 showed antibacterial activities against Helicobacter pylori, a causative pathogen of various gastric diseases, with minimum inhibitory concentration (MIC) values of 1-16 µg/mL.

PM2.5 induces cell cycle arrest through regulating mTOR/P70S6K1 signaling pathway.

Fine particulate matter (PM2.5) pollution has become a serious problem in China. This study aims to elucidate the toxicity mechanism of PM2.5. Protein levels were detected by western blotting and RT-qPCR, and cell cycle was detected by flow cytometry. The results showed that exposure to PM2.5 induces cell cycle arrest and downregulation of the expression of cyclin D1 protein. Moreover, the protein expression of thymidylate synthase (TS) enzyme was found to be downregulated and the mRNA expression of TS was upregulated after PM2.5 exposure. Knockout of TS gene promoted cell cycle arrest and downregulation of the expression of cyclin D1 protein after PM2.5 exposure. Our data further revealed that PM2.5 exposure downregulates the expression of TS and cyclin D1 partially through the downregulation of the mammalian target of rapamycin (mTOR)/P70S6K1 signaling pathway. Thus, these findings indicate that PM2.5-induced cell cycle arrest might be due to the downregulation of mTOR/P70S6K1 signaling pathway, and thus inhibits the expression of TS protein.

Determination of endogenous substance change in PM2.5-induced rat plasma and lung samples by UPLC-MS/MS method to identify potential markers for lung impairment.

Exposure to fine particulate matter (PM2.5) could induce lung impairment aggravation. Moreover, endogenous substances are known to play a significant role in lung impairment. Therefore, the research objectives was to investigate the influence of PM2.5-induced lung impairment on the levels of the eight endogenous substances, γ-aminobutyric acid (GABA), acetylcholine (ACh), glutamate (Glu), serotonin (5-HT), 5-hydroxyindole-3-acetic acid (5-HIAA), noradrenaline (NE), dopamine (DA), and 3, 4-dihydroxyphenylacetic acid (DOPAC). A sensitive UPLC-MS/MS method for the simultaneous determination of these endogenous substances in rat plasma and lung tissues was developed. The validated method was successfully applied for comparing profiles of analytes in rat plasma and lung tissues. The results indicated that five endogenous substances, namely, GABA, Ach, Glu, DA, and DOPAC, had a significant change in the rats with PM2.5-induced lung impairment.