The facile and controllable synthesis of ultrafine Sn nanocrystals loaded on carbon black for high-performance lithium storage.

Sn and C nanocomposites are ideal anode materials for high-energy and high-power density lithium ion batteries. However, their facile and controllable synthesis for practical applications is still a critical challenge. In this work, a facile one-step method is developed to controllably synthesize ultrafine Sn nanocrystals (< 5 nm) loaded on carbon black (Sn@C) through Na reducing SnCl4 by mechanical milling. Different from traditional up-down mechanical milling method, this method utilizes mechanical milling to trigger bottom-up reduction reaction of SnCl4. The in-situ formed Sn nanocrystals directly grow on carbon black, which results in the homogeneous composite and the size control of Sn nanocrystals. The obtained Sn@C electrode is revealed to possesses large lithium diffusion coefficient, low lithiation energy barrier and stable electrochemical property during cycle, thus showing excellent lithium storage performance with a high reversible capacity (942 mAh g-1 at a current density of 100 mA g-1), distinguished rate ability (480 mAh g-1 at 8000 mA g-1) and superb cycling performance (730 mAh g-1 at 1000 mA g-1 even after 1000 cycles).

PE/PPE mutations in the transmission of Mycobacterium tuberculosis in China revealed by whole genome sequencing.

OBJECTIVE: This study aims to examine the impact of PE/PPE gene mutations on the transmission of Mycobacterium tuberculosis (M. tuberculosis) in China. METHODS: We collected the whole genome sequencing (WGS) data of 3202 M. tuberculosis isolates in China from 2007 to 2018 and investigated the clustering of strains from different lineages. To evaluate the potential role of PE/PPE gene mutations in the dissemination of the pathogen, we employed homoplastic analysis to detect homoplastic single nucleotide polymorphisms (SNPs) within these gene regions. Subsequently, logistic regression analysis was conducted to analyze the statistical association. RESULTS: Based on nationwide M. tuberculosis WGS data, it has been observed that the majority of the M. tuberculosis burden in China is caused by lineage 2 strains, followed by lineage 4. Lineage 2 exhibited a higher number of transmission clusters, totaling 446 clusters, of which 77 were cross-regional clusters. Conversely, there were only 52 transmission clusters in lineage 4, of which 9 were cross-regional clusters. In the analysis of lineage 2 isolates, regression results showed that 4 specific gene mutations, PE4 (position 190,394; c.46G > A), PE_PGRS10 (839,194; c.744 A > G), PE16 (1,607,005; c.620T > G) and PE_PGRS44 (2,921,883; c.333 C > A), were significantly associated with the transmission of M. tuberculosis. Mutations of PE_PGRS10 (839,334; c.884 A > G), PE_PGRS11 (847,613; c.1455G > C), PE_PGRS47 (3,054,724; c.811 A > G) and PPE66 (4,189,930; c.303G > C) exhibited significant associations with the cross-regional clusters. A total of 13 mutation positions showed a positive correlation with clustering size, indicating a positive association. For lineage 4 strains, no mutations were found to enhance transmission, but 2 mutation sites were identified as risk factors for cross-regional clusters. These included PE_PGRS4 (338,100; c.974 A > G) and PPE13 (976,897; c.1307 A > C). CONCLUSION: Our results indicate that some PE/PPE gene mutations can increase the risk of M. tuberculosis transmission, which might provide a basis for controlling the spread of tuberculosis.

Reactive Oxygen Species Modulate Th17/Treg Balance in Chlamydia psittaci Pneumonia via NLRP3/IL-1ß/Caspase-1 Pathway Differentiation.

Chlamydia psittaci pneumonia (CPP) is a lung disease caused by the infection with the Chla-mydia psittaci bacterium, which can lead to severe acute respiratory distress syndrome and systemic symptoms. This study explored the specific mechanisms underlying the impact of reactive oxygen species (ROS) on the Th17/Treg balance in CPP. The levels of ROS and the differentiation ratio of Th17/Treg in the peripheral blood of healthy individuals and CPP patients were measured using ELISA and flow cytometry, respectively. The association between the ROS levels and Th17/Treg was assessed using Pearson correlation analysis. The ROS levels and the Th17/Treg ratio were measured in CD4+ T cells following H2O2 treatment and NLRP3 inhibition. The effects of H2O2 treatment and NLRP3 inhibition on the NLRP3/IL-1ß/caspase-1 pathway were observed using immunoblotting. Compared to the healthy group, the CPP group exhibited increased levels of ROS in the peripheral blood, an elevated ratio of Th17 differentiation, and a decreased ratio of Treg differentiation. ROS levels were positively correlated with the Th17 cell proportion but negatively correlated with the Treg cell proportion. The ROS levels and NLRP3/IL-1ß/caspase-1 expression were up-regulated in CD4+ T cells after H2O2 treatment. Furthermore, there was an increase in Th17 differentiation and a decrease in Treg differentiation. Conversely, the NLRP3/IL-1ß/caspase-1 pathway inhibition reversed the effects of H2O2 treatment, with no significant change in the ROS levels. ROS regulates the Th17/Treg balance in CPP, possibly through the NLRP3/IL-1ß/caspase-1 pathway. This study provides a new perspective on the development of immunotherapy for CPP.

Investigation of mediastinal lymph node dissection in clinical stage IA pure-solid non-small cell lung cancer patients.

OBJECTIVE: To explore the independent predictors of pathological mediastinal lymph node (pN2) metastasis in clinical stage IA (cIA) pure-solid non-small cell lung cancer (NSCLC) patients, and to find an appropriate method of mediastinal lymph node dissection. METHODS: This study retrospectively evaluated 533 cIA pure-solid NSCLC patients who underwent radical resection of lung cancer (lobectomy combined with systematic lymph node dissection) from January 2014 to December 2016. The relationship between clinicopathological characteristics and pN2 metastasis was analyzed, and the independent predictors of pN2 metastasis were determined by univariate and multivariate logistic regression analysis. We defined the new factor Y as composed of preoperative cT, CEA, and NSE. RESULTS: There were 72 cases (13.5%) of pN2 metastasis in cIA pure-solid NSCLC patients. Preoperative clinical tumor diameter (cT), serum CEA level, serum NSE level, and pathological status of station 10 lymph nodes were independent predictors of pN2 metastasis. Patients with cT ≤ 21.5 mm, CEA ≤ 3.85 ng/mL, NSE ≤ 13.40 ng/mL and negative station 10 lymph node group showed lower rates of pN2 metastasis. The new factor Y was an independent predictor of pN2 metastasis. Only 3 (2.1%) of 143 patients in the Y low-risk group showed pN2 metastasis. CONCLUSION: For patients with low risk of pN2 metastasis, it might be feasible to take lobe-specific lymph node sampling or systematic lymph node sampling. As for those with high risk of pN2 metastasis, systematic lymph node dissection would be recommended.

Iron-related gene mutations driving global Mycobacterium tuberculosis transmission revealed by whole-genome sequencing.

BACKGROUND: Iron plays a crucial role in the growth of Mycobacterium tuberculosis (M. tuberculosis). However, the precise regulatory mechanism governing this system requires further elucidation. Additionally, limited studies have examined the impact of gene mutations related to iron on the transmission of M. tuberculosis globally. This research aims to investigate the correlation between mutations in iron-related genes and the worldwide transmission of M. tuberculosis. RESULTS: A total of 13,532 isolates of M. tuberculosis were included in this study. Among them, 6,104 (45.11%) were identified as genomic clustered isolates, while 8,395 (62.04%) were classified as genomic clade isolates. Our results showed that a total of 12 single nucleotide polymorphisms (SNPs) showed a positive correlation with clustering, such as Rv1469 (ctpD, C758T), Rv3703c (etgB, G1122T), and Rv3743c (ctpJ, G676C). Additionally, seven SNPs, including Rv0104 (T167G, T478G), Rv0211 (pckA, A302C), Rv0283 (eccB3, C423T), Rv1436 (gap, G654T), ctpD C758T, and etgB C578A, demonstrated a positive correlation with transmission clades across different countries. Notably, our findings highlighted the positive association of Rv0104 T167G, pckA A302C, eccB3 C423T, ctpD C758T, and etgB C578A with transmission clades across diverse regions. Furthermore, our analysis identified 78 SNPs that exhibited significant associations with clade size. CONCLUSIONS: Our study reveals the link between iron-related gene SNPs and M. tuberculosis transmission, offering insights into crucial factors influencing the pathogenicity of the disease. This research holds promise for targeted strategies in prevention and treatment, advancing research and interventions in this field.

Multidrug-resistant Mycobacterium tuberculosis transmission in Shandong, China.

Multidrug-resistant tuberculosis (MDR-TB) has imposed a significant economic and health burden worldwide, notably in China. Using whole genome sequence, we sought to understand the mutation and transmission of MDR-TB in Shandong. A retrospective study of patients diagnosed with pulmonary tuberculosis in Shandong from 2009 to 2018 was conducted. To explore transmission patterns, we performed whole genome sequencing on MDR-TB isolates, identified genomic clusters, and assessed the drug resistance of TB isolates. Our study analyzed 167 isolates of MDR-TB, finding that 100 were clustered. The predominant lineage among MDR-TB isolates was lineage 2, specifically with a notable 88.6% belonging to lineage 2.2.1. Lineage 4 constituted a smaller proportion, accounting for 4.2% of the isolates. We discovered that Shandong has a significant clustering percentage for MDR-TB, with Jining having the highest percentage among all Shandong cities. The clustering percentages of MDR-TB, pre-extensively drug-resistant tuberculosis, and extensively drug-resistant tuberculosis were 59.9%, 66.0%, and 71.4%, respectively, and the clustering percentages increased with the expansion of the anti-TB spectrum. Isolates from genomic clusters 1 and 3 belonged to lineage 2.2.1 and showed signs of cross-regional transmission. The distribution of rrs A1401G and katG S315T mutations in lineage 2.2.1 and 2.2.2 strains differed significantly (P < .05). MDR-TB isolates with rpoB I480V, embA-12C > T, and rrs A1401G mutations showed a higher likelihood of clustering (P < .05). Our findings indicate a significant problem of local transmission of MDR-TB in Shandong, China. Beijing lineage isolates and some drug-resistant mutations account for the MDR-TB transmission in Shandong.

Design, Synthesis, and Anti-Osteoporotic Characterization of Arginine N-Glycosylated Teriparatide Analogs via the Silver-catalyzed Solid-Phase Glycosylation Strategy.

In spite of effective antiosteoporosis potency, teriparatide, a bone-building agent approved by the FDA (Food and Drug Administration), was proven to exhibit various side effects. In our previous work, we developed a universal strategy for synthesizing arginine N-glycosylated peptides termed silver-promoted solid-phase glycosylation (SSG) strategy. However, it is unknown whether the SSG strategy can be applied in the peptide drug design. Herein, we first reported the optimization of teriparatide via SSG strategy. Using Arg20 and/or Arg25 as the modifying positions, three series of arginine N-glycosylated teriparatide analogs were successfully synthesized, of which the introduced sugar groups included glucose, galactose, mannose, rhamnose, ribose, 2-acetamino-2-deoxy-glucose, xylose, lactose, and maltose. Among the 27 arginine N-glycosylated derivatives, Arg20-xylose and Arg25-maltose teriparatide analogs, termed PTH-1g and PTH-2i, respectively, indicated enhanced serum stability and significantly improved antiosteoporotic activities in vitro and in vivo compared with the native counterpart. They may serve as effective therapeutic candidates for treating osteoporosis.

State-of-the-Art Two-Dimensional Metal Phosphides for High Performance Lithium-ion Batteries: Progress and Prospects.

Lithium-ion batteries (LIBs) with high energy density, long cycle life and safety have earned recognition as outstanding energy storage devices, and have been used in extensive applications, such as portable electronics and new energy vehicles. However, traditional graphite anodes deliver low specific capacity and inferior rate performance, which is difficult to satisfy ever-increasing demands in LIBs. Very recently, two-dimensional metal phosphides (2D MPs) emerge as the cutting-edge materials in LIBs due to their overwhelming advantages including high theoretical capacity, excellent conductivity and short lithium diffusion pathway. This review summarizes the up-to-date advances of 2D MPs from typical structures, main synthesis methods and LIBs applications. The corresponding lithium storage mechanism, and relationship between 2D structure and lithium storage performance is deeply discussed to provide new enlightening insights in application of 2D materials for LIBs. Several potential challenges and inspiring outlooks are highlighted to provide guidance for future research and applications of 2D MPs.

Transmission dynamics and phylogeography of Mycobacterium tuberculosis in China based on whole-genome phylogenetic analysis.

OBJECTIVES: This study aimed to describe the lineage-specific transmissibility and epidemiological migration of Mycobacterium tuberculosis in China. METHODS: We curated a large set of whole-genome sequences from 3204 M. tuberculosis isolates, including thousands of newly sequenced genomes, and applied a series of metrics to compare the transmissibility of M. tuberculosis strains between lineages and sublineages. The countrywide transmission patterns of major lineages were explored. RESULTS: We found that lineage 2 (L2) was the most prevalent lineage in China (85.7%), with the major sublineage 2.2.1 (80.9%), followed by lineage 4 (L4) (13.8%), which comprises major sublineages 4.2 (1.5%), 4.4 (6.2%) and 4.5 (5.8%). We showed evidence for frequent cross-regional spread and large cluster formation of L2.2.1 strains, whereas L4 strains were relatively geographically restricted in China. Next, we applied a series of genomic indices to evaluate M. tuberculosis strain transmissibility and uncovered higher transmissibility of L2.2.1 compared with the L2.2.2 and L4 sublineages. Phylogeographic analysis showed that southern, eastern, and northern China were highly connected regions for countrywide L2.2.1 strain spread. CONCLUSIONS: The present study provides insights into the different transmission and migration patterns of the major M. tuberculosis lineages in China and highlights that transmissible L2.2.1 is a threat to tuberculosis control.

A novel iTreg-related signature for prognostic prediction in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer. Most patients are diagnosed at an advanced stage, therefore it is crucial to identify novel prognostic biomarkers for LUAD. As important regulatory cells, inducible regulatory T cells (iTregs) play a vital role in immune suppression and are important for the maintenance of immune homeostasis. This study explored the prognostic value and therapeutic effects of iTreg-related genes in LUAD. Data for LUAD patients, including immune infiltration data, RNA sequencing data, and clinical features, were acquired from The Cancer Genome Atlas, Gene Expression Omnibus, and Tumor Immune Single-cell Hub 2 databases. Immune-related subgroups with different infiltration patterns and iTreg-related genes were identified through univariate and multivariate Cox regression analyses and weighted correlation network analysis. Functional enrichment analyses were performed to explore the underlying mechanisms of iTreg-related genes. A prognostic risk signature was constructed using Cox regression analysis with the least absolute shrinkage and selection operator penalty. The ESTIMATE algorithm was applied to determine the immune status of LUAD patients. We applied the constructed signature to predict chemosensitivity and performed single-cell RNA sequencing analysis. The infiltration of iTregs was identified as an independent factor for predicting patient outcomes. We constructed a prognostic signature based on seven iTreg-related genes (GIMAP5, SLA, MS4A7, ZNF366, POU2AF1, MRPL12, and COL5A1), which was applied to subdivide patients into high- and low-risk subgroups. Our results revealed that patients in the iTreg-related low-risk subgroup had a better prognosis and possibly greater sensitivity to traditional chemotherapy. Our study provides a novel iTreg-related signature to elucidate the mechanisms underlying LUAD prognosis and promote individualized chemotherapy treatment.

Genomic analysis of lineage-specific transmission of multidrug resistance tuberculosis in China.

OBJECTIVES: We investigated the genetic diversities and lineage-specific transmission dynamics of multidrug-resistant tuberculosis (MDR-TB), with the goal of determining the potential factors driving the MDR epidemics in China. METHODS: We curated a large nationwide Mycobacterium tuberculosis (M. tuberculosis) whole genome sequence data set, including 1313 MDR strains. We reconstructed the phylogeny and mapped the transmission networks of MDR-TB across China using Bayesian inference. To identify drug-resistance variants linked to enhanced transmissibility, we employed ordinary least-squares (OLS) regression analysis. RESULT: The majority of MDR-TB strains in China belong to lineage 2.2.1. Transmission chain analysis has indicated that the repeated and frequent transmission of L2.2.1 plays a central role in the establishment of MDR epidemic in China, but no occurrence of a large predominant MDR outbreak was detected. Using OLS regression, the most common single nucleotide polymorphisms (SNPs) associated with resistance to isoniazid (katG_p.Ser315Thr and katG_p.Ser315Asn) and rifampicin (rpoB_p.Ser450Leu, rpoB_p.His445Tyr, rpoB_p.His445Arg, rpoB_p.His445Asp, and rpoB_p.His445Asn) were more likely to be found in L2 clustered strains. Several putative compensatory mutations in rpoA, rpoC, and katG were significantly associated with clustering. The eastern, central, and southern regions of China had a high level of connectivity for the migration of L2 MDR strains throughout the country. The skyline plot showed distinct population size expansion dynamics for MDR-TB lineages in China. CONCLUSION: MDR-TB epidemic in China is predominantly driven by the spread of highly transmissible Beijing strains. A range of drug-resistance mutations of L2 MDR-TB strains displayed minimal fitness costs and may facilitate their transmission.

Association between fatty acid metabolism gene mutations and Mycobacterium tuberculosis transmission revealed by whole genome sequencing.

BACKGROUND: Fatty acid metabolism greatly promotes the virulence and pathogenicity of Mycobacterium tuberculosis (M.tb). However, the regulatory mechanism of fatty acid metabolism in M.tb remains to be elucidated, and limited evidence about the effects of gene mutations in fatty acid metabolism on the transmission of M.tb was reported. RESULTS: Overall, a total of 3193 M.tb isolates were included in the study, of which 1596 (50%) were genomic clustered isolates. Most of the tuberculosis isolates belonged to lineage2(n = 2744,85.93%), followed by lineage4(n = 439,13.75%) and lineage3(n = 10,0.31%).Regression results showed that the mutations of gca (136,605, 317G > C, Arg106Pro; OR, 22.144; 95% CI, 2.591-189.272), ogt(1,477,346, 286G > C ,Gly96Arg; OR, 3.893; 95%CI, 1.432-10.583), and rpsA (1,834,776, 1235 C > T, Ala412Val; OR, 3.674; 95% CI, 1.217-11.091) were significantly associated with clustering; mutations in gca and rpsA were also significantly associated with clustering of lineage2. Mutation in arsA(3,001,498, 885 C > G, Thr295Thr; OR, 6.278; 95% CI, 2.508-15.711) was significantly associated with cross-regional clusters. We also found that 20 mutation sites were positively correlated with cluster size, while 11 fatty acid mutation sites were negatively correlated with cluster size. CONCLUSION: Our research results suggested that mutations in genes related to fatty acid metabolism were related to the transmission of M.tb. This research could help in the future control of the transmission of M.tb.

Sevoflurane attenuates proliferative and migratory activity of lung cancer cells via mediating the microRNA-100-3p/sterol O-Acyltransferase 1 axis.

Recently, evidence has shown that microRNA-100-3p (miR-100-3p) has been revealed as a tumor suppressor in diverse human diseases, while its capability in lung cancer warrants further validation. In this work, we aimed to discuss the impact of sevoflurane on biological functions of lung cancer cells by modulating the miR-100-3p/sterol O-acyltransferase 1 (SOAT1) axis. Lung cancer cell lines (A549 and H460) were treated with various concentrations of sevoflurane. Cell viability, proliferation, migration, and invasion were evaluated using MTT, colony formation, wound healing, and transwell assays. Moreover, miR-100-3p and SOAT1 expressions were evaluated by reverse transcription-quantitative polymerase chain reaction in lung cancer cells. The target interaction between miR-100-3p and SOAT1 was predicted by bioinformatics analysis and verified by the dual-luciferase reporter gene assay. The findings of our work demonstrated that sevoflurane impeded the abilities on viability, proliferation, migration, and invasion of A549 and H460 cells. The expression of miR-100-3p was reduced, and SOAT1 expression was elevated in lung cancer cells. miR-100-3p targeted SOAT1. Besides, sevoflurane could lead to expressed improvement of miR-100-3p or limitation of SOAT1. Downregulation of miR-100-3p or upregulation of SOAT1 restored the suppression of sevoflurane on abilities of viability, proliferation, migration, and invasion in A549 and H460 cells. In the rescue experiment, downregulation of SOAT1 reversed the impacts of downregulation of miR-100-3p on sevoflurane on lung cancer cells. Collectively, our study provides evidence that sevoflurane restrained the proliferation and invasion in lung cancer cells by modulating the miR-100-3p/SOAT1 axis. This article provides a new idea for further study of the pathogenesis of lung cancer.

Association between two-component systems gene mutation and Mycobacterium tuberculosis transmission revealed by whole genome sequencing.

BACKGROUND: Two-component systems (TCSs) assume a pivotal function in Mycobacterium tuberculosis (M.tuberculosis) growth. However, the exact regulatory mechanism of this system needs to be elucidated, and only a few studies have investigated the effect of gene mutations within TCSs on M.tuberculosis transmission. This research explored the relationship between TCSs gene mutation and the global transmission of (M.tuberculosis). RESULTS: A total of 13531 M.tuberculosis strains were enrolled in the study. Most of the M.tuberculosis strains belonged to lineage4 (n=6497,48.0%), followed by lineage2 (n=5136,38.0%). Our results showed that a total of 36 single nucleotide polymorphisms (SNPs) were positively correlated with clustering of lineage2, such as Rv0758 (phoR, C820G), Rv1747(T1102C), and Rv1057(C1168T). A total of 30 SNPs showed positive correlation with clustering of lineage4, such as phoR(C182A, C1184G, C662T, T758G), Rv3764c (tcrY, G1151T), and Rv1747 C20T. A total of 19 SNPs were positively correlated with cross-country transmission of lineage2, such as phoR A575C, Rv1028c (kdpD, G383T, G1246C), and Rv1057 G817T. A total of 41 SNPs were positively correlated with cross-country transmission of lineage4, such as phoR(T758G, T327G, C284G), kdpD(G1755A, G625C), Rv1057 C980T, and Rv1747 T373G. CONCLUSIONS: Our study identified that SNPs in genes of two-component systems were related to the transmission of M. tuberculosis. This finding adds another layer of complexity to M. tuberculosis virulence and provides insight into future research that will help to elucidate a novel mechanism of M. tuberculosis pathogenicity.

Clinical features of psittacosis in 46 Chinese patients / Características clínicas de 46 pacientes con psittacitis China

Background: Psittacosis is a relatively uncommon cause of community-acquired pneumonia, often leading to diagnostic difficulty.Methods: A retrospective study was conducted on the clinical features of psittacosis patients in China. Forty-six cases of Chlamydophila psittaci infection with atypical pneumonia of varying severity in the last two years were described retrospectively.Results: Fever, relative bradycardia, and other systemic upsets were the main clinical presentation. The most common radiographic abnormality was segmental or lobar shadowing or consolidation. The total white cell counts were usually normal or slightly increased. The concentration of creatine kinase, C reactive protein, and lactic dehydrogenase increased, while albumin decreased remarkably. These cases exhibited good recovery after being treated with tetracycline or quinolone antibiotics.Conclusion: These features may help differentiate psittacosis from other traditional bacterial pneumonia. However, they do not provide a definitive diagnosis. Psittacosis diagnosis must perform the whole-genome sequencing for Chlamydophila psittaci in respiratory, blood, or sputum specimens. Increased awareness of psittacosis can shorten diagnostic delays and improve patient outcomes.(AU)

Antecedentes: La psitacosis es una causa relativamente poco común de neumonía adquirida en la comunidad, y a menudo conduce a dificultades diagnósticas.Métodos: Se realizó un estudio retrospectivo sobre las características clínicas de los pacientes con psitacosis en China, en el que se describen retrospectivamente 46 casos de infección por Chlamydia psittaci con neumonía atípica de gravedad variable en los últimos dos años.Resultados: La fiebre, la bradicardia relativa y otros trastornos sistémicos fueron la presentación clínica principal. La anomalía radiográfica más común fue el sombreado o consolidación segmentaria o lobular. Los recuentos totales de glóbulos blancos fueron generalmente normales o ligeramente aumentados. Las concentraciones de creatina quinasa, proteína C reactiva y deshidrogenasa láctica aumentaron, mientras que la albúmina disminuyó notablemente. Estos casos mostraron una buena recuperación después de ser tratados con antibióticos de tetraciclina o quinolona.Conclusión: Estas características pueden ayudar a diferenciar la psitacosis de otras neumonías bacterianas tradicionales. Sin embargo, no proporcionan un diagnóstico definitivo. El diagnóstico de psitacosis debe realizar la secuenciación del genoma completo de Chlamydia psittaci en muestras respiratorias, sanguíneas o de esputo. Una mayor conciencia de la psitacosis puede acortar los retrasos en el diagnóstico y mejorar los resultados de los pacientes.(AU)

Benzyl stapled modification and anticancer activity of antimicrobial peptide A4K14-Citropin 1.1.

A4K14-Citropin 1.1 (GLFAVIKKVASVIKGL-NH2) is a derived antimicrobial peptide (AMP) with a more stable α-helical structure at the C-terminal compared to prototype Citropin 1.1 which was obtained from glandular skin secretions of Australian freetail lizards. In a previous report, A4K14-Citropin 1.1 has been considered as an anti-cancer lead compound. However, linear peptides are difficult to maintain stable secondary structure, resulted in poor pharmacokinetic properties. In this study, we designed and synthesized a series of benzyl-stapled derivatives of A4K14-Citropin 1.1. And their physical and chemical properties, as well as biological activity, were both explored. The result showed that AC-CCSP-2-o and AC-CCSP-3-o exhibited a higher degree of helicity and greater anti-cancer activity compared with the prototype peptide. Besides, there was no significant difference in the hemolytic effect between the stapled peptides and the prototype peptide. AC-CCSP-2-o and AC-CCSP-3-o could serve as promising anti-cancer lead compounds for the novel anti-cancer drug development.

Discovery of an orally effective double-stapled peptide for reducing ovariectomy-induced bone loss in mice.

Stapled peptides with significantly enhanced pharmacological profiles have emerged as promising therapeutic molecules due to their remarkable resistance to proteolysis and performance to penetrate cells. The all-hydrocarbon peptide stapling technique has already widely adopted with great success, yielding numerous potent peptide-based molecules. Based on our prior efforts, we conceived and prepared a double-stapled peptide in this study, termed FRNC-1, which effectively attenuated the bone resorption capacity of mature osteoclasts in vitro through specific inhibition of phosphorylated GSK-3ß. The double-stapled peptide FRNC-1 displayed notably improved helical contents and resistance to proteolysis than its linear form. Additionally, FRNC-1 effectively prevented osteoclast activation and improved bone density for ovariectomized (OVX) mice after intravenous injection and importantly, after oral (intragastric) administration. The double-stapled peptide FRNC-1 is the first orally effective peptide that has been validated to date as a therapeutic candidate for postmenopausal osteoporosis (PMOP).

microRNA-651-5p affects the proliferation, migration, and invasion of lung cancer cells by regulating Calmodulin 2 expression.

OBJECTIVE: Lung cancer is prevalent worldwide and a leading contributor to tumor death. This research intends to explore the molecular mechanism of the microRNA-651-5p (miR-651-5p)/Calmodulin 2 (CALM2) axis in the proliferation, migration, and invasion of lung cancer cells. METHODS: Lung cancer tissues and para-cancerous tissues were collected. The expression levels of miR-651-5p and CALM2 in lung cancer tissues and cells were tested, and the connection between miR-651-5p expression and clinicopathological characteristics of lung cancer patients was further analyzed. The binding sites between miR-651-5p and CALM2 were analyzed and validated. Lung cancer cell proliferation, migration, invasion, and apoptosis were examined. RESULTS: miR-651-5p was lowly expressed in lung cancer tissues and cells. miR-651-5p expression had no correlation with patients' age and gender but had a correlation with patients' tumor size, TNM stage, and lymph node metastasis. Overexpression of miR-651-5p repressed proliferative, migratory, and invasive behaviors of lung cancer cells. miR-651-5p targeted and negatively regulated CALM2 expression, and CALM2 reversed the inhibiting effects of miR-651-5p on lung cancer cell malignant behaviors, including proliferation, migration, and invasion. CONCLUSION: This study expounds that miR-651-5p affects the proliferation, migration, and invasion of lung cancer cells by regulating CALM2 expression.