[Research progress on chemical constituents and pharmacological effects of Kaixin Powder and predictive analysis of its Q-markers].

Kaixin Powder is a classic prescription for invigorating Qi, nourishing the mind, and calming the mind. It has pharmacological effects of improving learning and memory ability, resisting oxidation, delaying aging, and promoting the differentiation and regeneration of nerve cells. It is mainly used in the modern clinical treatment of amnesia, depression, dementia, and other diseases. The present paper reviewed the research progress on the chemical composition and pharmacological action of Kaixin Powder, predicted and analyzed its quality markers(Q-markers) according to the concept of Chinese medicine Q-markers, including transmission and traceability, specificity, effectiveness, measurability, and compound compatibility environment. The results suggested that sibiricose A5, sibiricose A6, polygalaxanthone Ⅲ, 3',6-disinapoylsucrose, tenuifoliside A, ginsenoside Rg_1, ginsenoside Re, ginsenoside Rb_1, pachymic acid, ß-asarone, and α-asarone could be used as Q-markers of Kaixin Powder. This study is expected to provide a scientific basis for establishing the quality control system and the whole process quality traceability system of Kaixin Powder compound preparations.

Adsorption-Catalysis-Conversion of Polysulfides in Sandwiched Ultrathin Ni(OH)2 -PANI for Stable Lithium-Sulfur Batteries.

Strong adsorption and catalysis for lithium polysulfides (LiPSs) are critical toward the electrochemical stability of Li-S batteries. Herein, a hollow sandwiched nanoparticle is put forward to enhance the adsorption-catalysis-conversion dynamic of sulfur species. The outer ultrathin Ni(OH)2 nanosheets not only confine LiPSs via both physical encapsulation and chemical adsorption, but also promote redox kinetics and accelerate the conversion of sulfur species, which is revealed by experiments and theoretical calculations. Meanwhile, the inner hollow polyaniline soft core provides a strong chemical bonding to LiPSs after vulcanization, which can chemically adsorpt LiPSs, and synergistically confine the shuttle effect. Moreover, the Ni(OH)2 nanosheets with a large specific area can enhance the wettability of electrolyte, and the flexible hollow sandwiched structure can accommodate the volume expansion, promoting sulfur utilization and structural stability. The obtained cathode exhibits excellent electrochemical performance with an initial discharge capacity of 1173 mAh g-1 and a small capacity decay of 0.08% per cycle even after 500 cycles at 0.2 C, among the best results of Ni(OH)2 -based materials for Li-S batteries. It is believed that the combination of adsorption-catalysis-conversion will shed a light on the development of cathode materials for stable Li-S batteries.

Identification of METTL3 as an Adverse Prognostic Biomarker in Hepatocellular Carcinoma.

INTRODUCTION: N6-methyladenosine (m6A), the most prominent mRNA modification, plays a critical role in many physiological and pathological processes. However, the roles of m6A RNA modification in hepatocellular carcinoma (HCC) remain largely unknown. MATERIALS AND METHODS: We investigated the mRNA expression and clinical significance of m6A-related genes using data from The Cancer Genome Atlas (TCGA) liver hepatocellular carcinoma cohort. Mutation, copy number variation (CNV), methylation, differential expression, and gene ontology analyses, gene set enrichment analysis and the construction of a competing endogenous RNA (ceRNA) regulatory network were performed to investigate the underlying mechanisms of the aberrant expression of m6A-related genes. RESULTS: m6A-related genes were frequently dysregulated in cancers but with a cancer-specific pattern. METTL3, YTHDF2, and ZC3H13 were found to be independent prognostic factors of overall survival (OS); however, only METTL3 was found to be an independent prognostic factor of recurrence-free survival (RFS). Joint effects analysis showed the predictive capacity of combining METTL3, YTHDF2, and ZC3H13 for HCC OS. Then the potential mechanisms of METTL3 were further explored due to its prognostic role in both OS and RFS. CNV and DNA methylation, but not somatic mutations, might contribute to the abnormal upregulation of METTL3 in HCC. Significantly altered genes, microRNAs, and lncRNAs were identified, and a ceRNA regulatory network was constructed to explain the upregulation of METTL3 in HCC. CONCLUSIONS: Our study identified several m6A-related genes, especially METTL3, that could be potential prognostic biomarkers in HCC.

The anti-inflammatory effect of ent-kaur-15-en-17-al-18-oic acid on lipopolysaccharide-stimulated RAW264.7 cells associated with NF-κB and P38/MAPK pathways.

Ent-kaur-15-en-17-al-18-oic acid (LL-3) was demonstrated that it can inhibit LPS-induced nitric oxide (NO) production and macrophage migration, maintain homeostasis of oxidative stress, including increased mitochondrial membrane potential (MMP), decreased levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and maintenance of superoxide dismutase (SOD) and glutathione (GSH) activities and inhibit oxidative stress-induced P38 and nuclear factor κB (NF-κB) pathways to decrease inducible nitric oxide synthase (iNOS), cyclooxygense-2 (COX-2), and tumour necrosis factor (TNF)-α mRNA expressions without marked cytotoxicity. These findings revealed that LL-3 could serve as a candidate lead compound for further studying anti-inflammatory therapies.[Formula: see text].

Simultaneous measurement of tadehaginoside and its principal metabolite in rats by HPLC-MS/MS and its application in pharmacokinetics and tissue distribution study.

CONTEXT: Tadehaginoside, an active ingredient isolated from Tadehagi triquetrum (Linn.) Ohashi (Leguminosae), exhibited various biological activities. However, the pharmacokinetics and tissue distribution which affect tadehaginoside's therapeutic actions and application remain elusive. OBJECTIVE: To clarify the metabolism of tadehaginoside in vivo. MATERIALS AND METHODS: The pharmacokinetics and tissue distribution of tadehaginoside and its metabolite p-hydroxycinnamic acid (HYD) were investigated using LC-MS/MS. Pharmacokinetic parameters were determined in 10 Sprague-Dawley rats divided into two groups, the intravenous group (5 mg/kg) and the oral group (25 mg/kg). For the tissue-distribution study, 20 rats were intravenously given tadehaginoside (5 mg/kg) before the experiment (n = 4). Biological samples were collected before drug administration (control group) and after drug administration. RESULTS: The linearity, accuracy, precision, stability, recovery and matrix effect of the method were well-validated and the results satisfied the requirements of biological sample measurement. Treatment with tadehaginoside via intragastric and intravenous administration, the calculated Cmax in rats was 6.01 ± 2.14 ng/mL and 109.77 ± 4.29 ng/mL, and Tmax was 0.025 ± 0.08 h and 0.08 h, respectively. The results indicated that the quick absorption of tadehaginoside was observed following intravenous administration, and tadehaginoside in plasma of rats with intragastric administration showed relatively low concentration may be due to the formation of its metabolite. Tissue-distribution study indicated that kidney and spleen were the major distribution organs for tadehaginoside in rats and there was no long-term accumulation in most tissues. DISCUSSION AND CONCLUSION: These results could provide clues for exploring the bioactivity of tadehaginoside based on its pharmacokinetic characteristics.

[Review of chemical composition, pharmacological effects, and clinical application of Salviae Miltiorrhizae Radix et Rhizoma and prediction of its Q-markers].

Salviae Miltiorrhizae Radix et Rhizoma is a Chinese herbal medicine that promotes blood circulation to remove blood stasis, nourishes blood to tranquilize the mind, and cools blood to disperse carbuncles. Salviae Miltiorrhizae Radix et Rhizoma has microcirculation-improving, blood vessel-dilating, atherosclerosis-preventing, anti-inflammatory, anti-tumor, and blood pressure-and blood lipid-lowering activities. As research progresses, the chemical composition, pharmacological effect, and clinical application of Salviae Miltiorrhizae Radix et Rhizoma have attracted much attention. We reviewed the research progress in this field. Based on the concept of quality marker(Q-marker) in traditional Chinese medicine, the Q-markers of Salviae Miltiorrhizae Radix et Rhizoma were predicted and analyzed from the aspects of quality transfer, traceability, ingredient specificity, association between ingredients and pharmacological effects, ingredient predictability, and compounding environment. This review provides a scientific basis for the quality control of Salviae Miltiorrhizae Radix et Rhizoma and its preparations.

Identification of a four-gene metabolic signature predicting overall survival for hepatocellular carcinoma.

While hundreds of consistently altered metabolic genes had been identified in hepatocellular carcinoma (HCC), the prognostic role of them remains to be further elucidated. Messenger RNA expression profiles and clinicopathological data were downloaded from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma and GSE14520 data set from the Gene Expression Omnibus database. Univariate Cox regression analysis and lasso Cox regression model established a novel four-gene metabolic signature (including acetyl-CoA acetyltransferase 1, glutamic-oxaloacetic transaminase 2, phosphatidylserine synthase 2, and uridine-cytidine kinase 2) for HCC prognosis prediction. Patients in the high-risk group shown significantly poorer survival than patients in the low-risk group. The signature was significantly correlated with other negative prognostic factors such as higher α-fetoprotein. The signature was found to be an independent prognostic factor for HCC survival. Nomogram including the signature shown some clinical net benefit for overall survival prediction. Furthermore, gene set enrichment analyses revealed several significantly enriched pathways, which might help explain the underlying mechanisms. Our study identified a novel robust four-gene metabolic signature for HCC prognosis prediction. The signature might reflect the dysregulated metabolic microenvironment and provided potential biomarkers for metabolic therapy and treatment response prediction in HCC.

Identification of a six-gene signature predicting overall survival for hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) remains a major challenge for public health worldwide. Considering the great heterogeneity of HCC, more accurate prognostic models are urgently needed. To identify a robust prognostic gene signature, we conduct this study. MATERIALS AND METHODS: Level 3 mRNA expression profiles and clinicopathological data were obtained in The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC). GSE14520 dataset from the gene expression omnibus (GEO) database was downloaded to further validate the results in TCGA. Differentially expressed mRNAs between HCC and normal tissue were investigated. Univariate Cox regression analysis and lasso Cox regression model were performed to identify and construct the prognostic gene signature. Time-dependent receiver operating characteristic (ROC), Kaplan-Meier curve, multivariate Cox regression analysis, nomogram, and decision curve analysis (DCA) were used to assess the prognostic capacity of the six-gene signature. The prognostic value of the gene signature was further validated in independent GSE14520 cohort. Gene Set Enrichment Analyses (GSEA) was performed to further understand the underlying molecular mechanisms. The performance of the prognostic signature in differentiating between normal liver tissues and HCC were also investigated. RESULTS: A novel six-gene signature (including CSE1L, CSTB, MTHFR, DAGLA, MMP10, and GYS2) was established for HCC prognosis prediction. The ROC curve showed good performance in survival prediction in both the TCGA HCC cohort and the GSE14520 validation cohort. The six-gene signature could stratify patients into a high- and low-risk group which had significantly different survival. Cox regression analysis showed that the six-gene signature could independently predict OS. Nomogram including the six-gene signature was established and shown some clinical net benefit. Furthermore, GSEA revealed several significantly enriched oncological signatures and various metabolic process, which might help explain the underlying molecular mechanisms. Besides, the prognostic signature showed a strong ability for differentiating HCC from normal tissues. CONCLUSIONS: Our study established a novel six-gene signature and nomogram to predict overall survival of HCC, which may help in clinical decision making for individual treatment.

Actinomycin V Suppresses Human Non-Small-Cell Lung Carcinoma A549 Cells by Inducing G2/M Phase Arrest and Apoptosis via the p53-Dependent Pathway.

Actinomycin V, extracted and separated from marine-derived actinomycete Streptomyces sp., as the superior potential replacement of actinomycin D (which showed defect for its hepatotoxicity) has revealed an ideal effect in the suppression of migration and invasion in human breast cancer cells as referred to in our previous study. In this study, the involvement of p53 in the cell cycle arrest and pro-apoptotic action of actinomycin V was investigated in human non-small-cell lung carcinoma A549 cells. Results from the 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide assay showed that cytotoxic activity of actinomycin V on A549 cells (with wild-type p53) was stronger than the NCI-H1299 cells (p53-deficient). Actinomycin V upregulated both of the protein and mRNA expression levels of p53, p21Waf1/Cip1 and Bax in A549 cells. For this situation, actinomycin V decreased the M-phase related proteins (Cdc2, Cdc25A and Cyclin B1) expression, arrested cells in G2/M phase and subsequently triggered apoptosis by mediating the Bcl-2 family proteins' expression (Bax and Bcl-2). Furthermore, the effects of cell cycle arrest and apoptosis in A549 cells which were induced by actinomycin V could be reversed by the pifithrin-α, a specific inhibitor of p53 transcriptional activity. Collectively, our results suggest that actinomycin V causes up-regulation of p53 by which the growth of A549 cells is suppressed for cell cycle arrest and apoptosis.

Protective effects of 3ß-angeloyloxy-8ß, 10ß-dihydroxyeremophila-7(11)-en-12, 8α-lactone on paraquat-induced oxidative injury in SH-SY5Y cells.

3ß-Angeloyloxy-8ß,10ß-dihydroxyeremophila-7(11)-en-12,8α-lactone (FJ1) inhibited effectively paraquat (PQ)-induced injury in SH-SY5Y cells. In this way, FJ1 was shown to reverse the PQ-induced activation of caspase-9 and caspase-3, the increase in Bax/Bcl-2 ratio, and the release of cytochrome c. The mechanism was associated with a reduction of oxidative stress, including the decrease in the levels of ROS and MDA and maintaining the activity of SOD and GSH. Taken together, findings revealed that FJ1 had protective effects against PQ-induced injury via attenuating the oxidative stress in SH-SY5Y cells, which suggested that FJ1 might be a candidate for further evaluation against neurodegeneration in Parkinson's disease.

Ivalin Induces Mitochondria-Mediated Apoptosis Associated with the NF-κB Activation in Human Hepatocellular Carcinoma SMMC-7721 Cells.

Ivalin, a natural compound isolated from Carpesium divaricatum, showed excellent microtubule depolymerization activities among human hepatocellular carcinoma in our previous work. Here, we investigated its functions on mitochondria-mediated apoptosis in hepatocellular carcinoma SMMC-7721 cells. DAPI (4',6-diamidino-2-phenylindole) staining, annexin V-fluorexcein isothiocyanate (FITC) apoptosis detection, and western blotting were applied to explore the apoptotic effect of Ivalin. Next, the induction effect of Ivalin on the mitochondrial pathway was also confirmed via a series of phenomena including the damage of mitochondria membrane potential, mitochondria cytochrome c escape, cleaved caspase-3 induction, and the reactive oxygen species generation. In this connection, we understood that Ivalin induced apoptosis through the mitochondrial pathway and the overload of reactive oxygen species. Furthermore, we found that the activation of nuclear factor-κB (NF-κB) and subsequent p53 induction were associated with the apoptotic effect of Ivalin. These data confirmed that Ivalin might be a promising pro-apoptotic compound that can be utilized as a potential drug for clinical treatment.

What explains high plant richness in East Asia? Time and diversification in the tribe Lysimachieae (Primulaceae).

What causes the disparity in biodiversity among regions is a fundamental question in biogeography, ecology, and evolutionary biology. Evolutionary and biogeographic processes (speciation, extinction, dispersal) directly determine species richness patterns, and can be studied using integrative phylogenetic approaches. However, the strikingly high richness of East Asia relative to other Northern Hemisphere regions remains poorly understood from this perspective. Here, for the first time, we test two general hypotheses (older colonization time, faster diversification rate) to explain this pattern, using the plant tribe Lysimachieae (Primulaceae) as a model system. We generated a new time-calibrated phylogeny for Lysimachieae (13 genes, 126 species), to estimate colonization times and diversification rates for each region and to test the relative importance of these two factors for explaining regional richness patterns. We find that neither time nor diversification rates alone explain richness patterns among regions in Lysimachieae. Instead, a new index that combines both factors explains global richness patterns in the group and their high East Asian biodiversity. Based on our results from Lysimachieae, we suggest that the high richness of plants in East Asia may be explained by a combination of older colonization times and faster diversification rates in this region.

Ivalin Inhibits Proliferation, Migration and Invasion by Suppressing Epithelial Mesenchymal Transition in Breast Cancer Cells.

Ivalin, an eudesmane-type sesquiterpene compound, was isolated from the Chinese herb Carpesium divaricatum in our chemistry group. In this study, we investigated the anti-migration and anti-invasion activities and underlying mechanisms of Ivalin in breast cancer cells in vitro. Cell viability was evaluated using the MTT assay, Western blotting was used to determine the expression of E-cadherin, N-cadherin, vimentin and ZEB1, and mRNA levels were analyzed by qPCR. The anti-migration and anti-invasion effects of Ivalin were measured by wound-healing and Transwell assays. In this connection, Ivalin treatment reduced the mRNA and protein expressions of ZEB1 as well as N-cadherin and vimentin expression in various breast cancer cells. E-cadherin expression was enhanced by Ivalin in the same cells, which implied that Ivalin depressed the process of epithelial-to-mesenchymal transition (EMT). Our results revealed that Ivalin significantly inhibited cell proliferation, migration and invasion in breast cancer cells in a dose-dependent manner in vitro. This study suggests that Ivalin may merit further investigation as a potential therapeutic leading compound for the treatment of breast cancer migration and invasion.

Characterization of Novel Microsatellite Loci for Primula poissonii (Primulaceae) Using High-Throughput Sequencing Technology.

Primula poissonii (Primulaceae) is a perennial herb, widely distributed in the Hengduan Mountain region of Southwest China. In this study, Roche 454 pyrosequencing was used to isolate microsatellite markers. A total of 4528 unique sequences were identified from 68,070 unique reads. Of these, eighty-seven microsatellite loci were screened for utility using two criteria: successful PCR amplification and variation of these loci within three wild P. poissonii populations. Twenty loci were successfully amplified and exhibited polymorphic alleles. The number of observed alleles ranged from 1 to 9 with an average of 3.5. The observed and expected heterozygosities ranged from 0.087 to 1.000 and from 0.124 to 0.828, respectively. Among these SSR loci, only the P69 locus could not be cross-amplified successfully in two closely related species P. wilsonii and P. anisodora. The microsatellite loci developed in this study will be useful for studying genetic diversity and speciation events between P. poissonii and closely related Primula species.

The Gß-like protein CpcB is required for hyphal growth, conidiophore morphology and pathogenicity in Aspergillus fumigatus.

CpcB (cross pathway control B) encodes a yeast Cpc2 and mammalian RACK1 (receptor for activated protein kinase C) ortholog, which is a WD repeat protein with functional homology to the ß subunit of heterotrimeric G proteins in Aspergillus fumigatus. Previous study has reported that CpcB governs growth and development in both A. fumigatus and Aspergillus nidulans. However, little is known about the functional identities of CpcB orthologs and their relationships with G protein complexes. In this study, we verified that cytoplasmic AfCpcB acts as a Gß-like protein ortholog and plays important roles in hyphal growth, conidiophore morphology, cell wall integrity, and virulence in A. fumigatus. Furthermore, double deletion of AfcpcB and AfgpaB (Gα) causes a similar phenotype to AfgpaB mutant with abnormal multiple septa conidiophores but exhibits sparse conidiation with white and fluffy colonies. Thus, the exacerbated conidiation defect suggests that AfcpcB has its own specific function compared to the Gα subunit of AfgpaB or the G-protein complex. In addition, complementation assays using AfcpcB orthologs of A. nidulans and yeasts (Saccharomyces cerevisiae, Schizosaccharomyces pombe, Candida albicans) suggest that all tested fungal AfcpcB orthologs under the A. fumigatus native promoter can largely restore hyphal growth defects in AfcpcB deletion mutant, but only the A. nidulans cpcB ortholog completely rescues the ΔAfcpcB conidiation defect, suggesting that CpcB acts as a Gß-like protein ortholog in the Aspergilli, but may have unique and important unexplored functions that required for conidiation, which is absent in yeast.

Repetitive infusion of levosimendan in patients with chronic heart failure: a meta-analysis.

BACKGROUND: Repetitive or intermittent levosimendan infusion is gradually becoming more commonly considered for patients with advanced chronic heart failure. However, previous randomized controlled studies (RCTs) reported conflicting results on the effects of levosimendan when administered repetitively. The aim of this meta-analysis was to generate up-to-date evidence to assess the effect of levosimendan in this group of patients. MATERIAL AND METHODS: A literature review identified 8 qualified studies. A meta-analysis was performed to assess mortality and left ventricular ejection fraction (LVEF). RESULTS: Use of levosimendan contributed to significantly reduced mortality at the end of mid-term follow-up. The mortality rates in levosimendan and control group were 23 of 226 (10.2%) and 53 of 198 (26.8%), respectively (RR: 0.40, 95%CI: 0.26-0.63, P<0.0001). The trend of significantly decreased mortality was observed in levosimendan vs. placebo subgroup (RR: 0.28, 95%CI: 0.15-0.54, P=0.0001, I2=0%) but not in levosimendan vs. dobutamine, PGE1, or furosemide subgroup (p=0.19, p=0.64 and p=0.25, respectively). Levosimendan also contributed to significantly improved LVEF improvement at the end of follow-up (mean difference: 3.69%, 95CI: 0.92-6.45%, p=0.009). CONCLUSIONS: Intermittent or repetitive levosimendan infusion might be a promising strategy to reduce mortality and improve LVEF in patients with advanced chronic, but not necessarily acutely decompensated, heart failure to maintain disease stability.

Metabolomics in cirrhosis: Recent advances and opportunities.

Liver cirrhosis (LC) represents a significant hepatic disorder that persistently commands the attention of the scientific community, especially concerning its pathogenesis and therapeutic approaches. Metabolomics, the comprehensive profiling of an organism's metabolome, has been increasingly applied in the research of cirrhosis over the past decade. This review summarizes the recent advancements and applications of metabolomics within the context of LC research, in recent five years. It highlights the role of metabolomics in the diagnosis of LC, the assessment of prognostic markers, and the evaluation of therapeutic outcomes. The discussion focuses on the potential and challenges of metabolomics in LC research, including the evolution of analytical technologies, advancements in bioinformatics, and the challenges impeding clinical implementation. Additionally, the review anticipates the forthcoming developments in metabolomics related to LC research, with the objective of facilitating innovative approaches for early detection and intervention in LC.

Engineered endolysin of Klebsiella pneumoniae phage is a potent and broad-spectrum bactericidal agent against "ESKAPEE" pathogens.

The rise of antimicrobial resistance in ESKAPEE pathogens poses significant clinical challenges, especially in polymicrobial infections. Bacteriophage-derived endolysins offer promise in combating this crisis, but face practical hurdles. Our study focuses on engineering endolysins from a Klebsiella pneumoniae phage, fusing them with ApoE23 and COG133 peptides. We assessed the resulting chimeric proteins' bactericidal activity against ESKAPEE pathogens in vitro. ApoE23-Kp84B (CHU-1) reduced over 3 log units of CFU for A. baumannii, E. faecalis, K. pneumoniae within 1 h, while COG133-Kp84B (CHU-2) showed significant efficacy against S. aureus. COG133-L1-Kp84B, with a GS linker insertion in CHU-2, exhibited outstanding bactericidal activity against E. cloacae and P. aeruginosa. Scanning electron microscopy revealed alterations in bacterial morphology after treatment with engineered endolysins. Notably, CHU-1 demonstrated promising anti-biofilm and anti-persister cell activity against A. baumannii and E. faecalis but had limited efficacy in a bacteremia mouse model of their coinfection. Our findings advance the field of endolysin engineering, facilitating the customization of these proteins to target specific bacterial pathogens. This approach holds promise for the development of personalized therapies tailored to combat ESKAPEE infections effectively.

ApoE Mimetic Peptide COG1410 Kills Mycobacterium smegmatis via Directly Interfering ClpC's ATPase Activity.

Antimicrobial peptides (AMPs) hold promise as alternatives to combat bacterial infections, addressing the urgent global threat of antibiotic resistance. COG1410, a synthetic peptide derived from apolipoprotein E, has exhibited potent antimicrobial properties against various bacterial strains, including Mycobacterium smegmatis. However, our study reveals a previously unknown resistance mechanism developed by M. smegmatis against COG1410 involving ClpC. Upon subjecting M. smegmatis to serial passages in the presence of sub-MIC COG1410, resistance emerged. The comparative genomic analysis identified a point mutation in ClpC (S437P), situated within its middle domain, which led to high resistance to COG1410 without compromising bacterial fitness. Complementation of ClpC in mutant restored bacterial sensitivity. In-depth analyses, including transcriptomic profiling and in vitro assays, uncovered that COG1410 interferes with ClpC at both transcriptional and functional levels. COG1410 not only stimulated the ATPase activity of ClpC but also enhanced the proteolytic activity of Clp protease. SPR analysis confirmed that COG1410 directly binds with ClpC. Surprisingly, the identified S437P mutation did not impact their binding affinity. This study sheds light on a unique resistance mechanism against AMPs in mycobacteria, highlighting the pivotal role of ClpC in this process. Unraveling the interplay between COG1410 and ClpC enriches our understanding of AMP-bacterial interactions, offering potential insights for developing innovative strategies to combat antibiotic resistance.

[Temporal Evolution and Source Appointment of Black Carbon Aerosol in Ordos During Summer and Autumn 2019].

In this study, black carbon (BC) aerosols were continuously observed using a seven-channel aethalometer (AE-33) in Ordos from August 12 to October 4, 2019; using this data combined with article matter (PM), pollutant gas, and meteorological element data; a HYSPLIT model; and potential source contribution function (PSCF) and concentration-weighted trajectory (CWT) models, we analyzed the temporal evolution and potential source appointment and main influence areas of BC. The results showed that the average of ρ(BC) was 882 ng·m-3, accounting for 6.08% of PM2.5. The ρ(BC) was mainly concentrated at 200-1000 ng·m-3, accounting for 55.9% of the total samples. In different BC mass concentration ranges, BCliquid was the mainstay, with an average proportion of 86%. The diurnal variations in BC and PM2.5 showed unimodal distributions, with peaks at 08:00 and 10:00, respectively, and peak concentrations increased by 24.3% and 47.2%, respectively. The diurnal variation in BCsolid showed a bimodal distribution, with peaks at 08:00 and 20:00, respectively. The diurnal variation in the BCliquid showed a unimodal distribution with a peak at 08:00. The strong correlation between BC and NO2 indicated a greater impact of vehicle emissions on BC concentration, whereas the weak correlation between BC and SO2 indicated a lower impact of industrial emissions on BC concentration. The dominant air masses affecting the Ordos could be divided into four categories. The southern air masses (35.6%) had the highest mass concentration of atmospheric pollutants, followed by the local air masses (26.9%) and the northwest air masses (18.8%), and the northeast air masses (18.7%) had the lowest mass concentration of pollutants. The influence of the Ordos on the downstream areas was mainly divided into the northeast air masses (40.9%), the northwest air masses (30.4%), and the southeast air masses (28.7%). High CWT value areas of BC were mainly located in the southern Yan'an-Tongchuan-Baoji-Hanzhong areas and Lvliang-Linfen-Sanmenxia-Nanyang areas. They were two long and narrow transmission belts with a weight mass concentration exceeding 1400 ng·m-3. High CWT value areas of BC had the greatest impact on the Wuhai-Bayannaoer-Baotou-Hohhot regions, with a weight concentration exceeding 900 ng·m-3. The long-range transportation of BC could reach the Yulin-Yan'an-Tongchuan-Baoji areas in the south, the Shuozhou-Datong-Beijing areas in the east, and the Xilin Gol League-Xing'an League-Hulunbuir areas in the northeast.