Multi-channel synthetic aperture infrared imaging and experimental research.

The synthetic aperture infrared radio imaging method based on laser local oscillator coherent detection has potential application value for astronomical observations. This paper studies the multi-channel synthetic aperture infrared imaging method and conducts experimental verification using a principle prototype. In the short-wave infrared band, five beam-expanding fiber collimators are used to build an observation structure of five laser local oscillator coherent detection channels at a near-field distance of 5 m to carry out physical experiments. The laser local oscillator wavelength is 1.55 µm, and the AD sampling rate is 4 GHz. For the infrared radiation source signal, the phase relationship of the infrared signals between channels acquired by the prototype principle is stable, and the five-channel synthetic aperture imaging results are consistent with the computer simulated results. The experiment verified the effectiveness of the laser local oscillator comprehensive aperture infrared radio imaging method.

[Genotype and epidemiological characteristics of human metapneumovirus among hospitalized cases of acute respiratory infection in children in Changchun City, Jilin Province from 2019 to 2023].

Objective: To investigate the genotype and epidemiological characteristics of human metapneumovirus (HMPV) among hospitalized cases with acute respiratory infections (ARI) in children in Changchun City, Jilin Province, China. Methods: From June 2019 to June 2023, throat swabs of ARI inpatients in Changchun Children's Hospital were collected, and their epidemiological and clinical information were also collected. Quantitative reverse transcription-PCR was used to identify HMPV-positive cases, followed by the amplification of the G gene and genetic analysis in the HMPV-positive cases. Results: A total of 3 311 children hospitalized with ARI were included in this study. Their age ranged from 0 to 17 years old, and the M (Q1, Q3) of age was 2 (1, 3) years. About 1 811 (54.70%) cases were males. A total of 167 HMPV-positive cases were detected with a positive rate of 5.04%, of which 92.81% (155/167) were children under 5 years old. The positive rate of HMPV in 2019 was 6.37% (30/471), which dropped to the lowest in 2020 (2.31%, 10/432). The HMPV-positive rate was then rebounded in 2021 (4.70%, 60/1 277) and 2022 (4.56%, 21/461), which increased to 6.87% (46/670) in 2023. The difference in HMPV-positive rate among each year was statistically significant (P<0.05). The prevalence peak of HMPV varied in different years, showing either a unimodal or bimodal distribution in one year. A total of 79 HMPV G gene sequences were obtained, of which subtype A and subtype B accounted for 48.10% and 51.90%, respectively. All of the subtype A sequences were clarified as A2c duplicated variants, and subtype B was mainly B2 genotype. Besides, subtypes A and B were prevalent alone or co-circulated in different years, and there was a subtype replacement pattern in HMPV. Conclusion: The positive rate of HMPV in hospitalized ARI cases in children is significantly different from 2019 to 2023 in Changchun City. Notably, there are certain switch patterns of HMPV subtypes A and B in different years.

[Epidemiological characteristics of human respiratory syncytial virus among acute respiratory infection cases in 16 provinces of China from 2009 to 2023].

Objective: To understand the epidemiological characteristics of human respiratory syncytial virus (HRSV) among acute respiratory infection (ARI) cases in 16 provinces of China from 2009 to 2023. Methods: The data of this study were collected from the ARI surveillance data from 16 provinces in China from 2009 to 2023, with a total of 28 278 ARI cases included in the study. The clinical specimens from ARI cases were screened for HRSV nucleic acid from 2009 to 2023, and differences in virus detection rates among cases of different age groups, regions, and months were analyzed. Results: A total of 28 278 ARI cases were enrolled from January 2009 to September 2023. The age of the cases ranged from<1 month to 112 years, and the age M (Q1, Q3) was 3 years (1 year, 9 years). Among them, 3 062 cases were positive for HRSV nucleic acid, with a total detection rate of 10.83%. From 2009 to 2019, the detection rate of HRSV was 9.33%, and the virus was mainly prevalent in winter and spring. During the Corona Virus Disease 2019 (COVID-19) pandemic, the detection rate of HRSV fluctuated between 6.32% and 18.67%. There was no traditional winter epidemic peak of HRSV from the end of 2022 to the beginning of 2023, and an anti-seasonal epidemic of HRSV occurred from April to May 2023. About 87.95% (2 693/3 062) of positive cases were children under 5 years old, and the difference in the detection rate of HRSV among different age groups was statistically significant (P<0.001), showing a decreasing trend of HRSV detection rate with the increase of age (P<0.001). Among them, the HRSV detection rate (25.69%) was highest in children under 6 months. Compared with 2009-2019, the ranking of HRSV detection rates in different age groups changed from high to low between 2020 and 2023, with the age M (Q1, Q3) of HRSV positive cases increasing from 1 year (6 months, 3 years) to 2 years (11 months, 3 years). Conclusion: Through 15 years of continuous HRSV surveillance analysis, children under 5 years old, especially infants under 6 months old, are the main high-risk population for HRSV infection. During the COVID-19 pandemic, the prevalence and patterns of HRSV in China have changed.

Global, regional prevalence, and risk factors of osteoporosis according to the World Health Organization diagnostic criteria: a systematic review and meta-analysis.

This systematic review and meta-analysis estimated the global, regional prevalence, and risk factors of osteoporosis. Prevalence varied greatly according to countries (from 4.1% in Netherlands to 52.0% in Turkey) and continents (from 8.0% in Oceania to 26.9% in Africa). Osteoporosis is a common metabolic bone disorder in the elderly, usually resulting in bone pain and an increased risk of fragility fracture, but few summarized studies have guided global strategies for the disease. Therefore, we pooled the epidemiologic data to estimate the global, regional prevalence, and potential risk factors of osteoporosis. We conducted a comprehensive literature search through PubMed, EMBASE, Web of Science, and Scopus, to identify population-based studies that reported the prevalence of osteoporosis based on the World Health Organization (WHO) criteria. Meta-regression and subgroup analyses were used to explore the sources of heterogeneity. The study was registered in the PROSPERO database (CRD42021285555). Of the 57,933 citations evaluated, 108 individual studies containing 343,704 subjects were included. The global prevalence of osteoporosis and osteopenia was 19.7% (95%CI, 18.0%-21.4%) and 40.4% (95%CI, 36.9%-43.8%). Prevalence varied greatly according to countries (from 4.1% in Netherlands to 52.0% in Turkey) and continents (from Oceania 8.0% to 26.9% in Africa). The prevalence was higher in developing countries (22.1%, 95%CI, 20.1%-24.1%) than in developed countries (14.5%, 95%CI, 11.5%-17.7%). Our study indicates a considerable prevalence of osteoporosis among the general population based on WHO criteria, and the prevalence varies substantially between countries and regions. Future studies with robust evidence are required to explore risk factors to provide effective preventive strategies for the disease.

[Analysis of common viral infection in surveillance cases of febrile respiratory syndrome in 9 provinces of China from 2009 to 2021].

Objective: To understand the common viral infection among the surveillance cases of fever respiratory syndrome (FRS) in nine provinces in China. Methods: The research data were obtained from nine provinces (Anhui, Beijing, Guangdong, Hebei, Hunan, Jilin, Shandong, Shaanxi and Xinjiang) in the "Infectious Disease Surveillance Technology Platform Information Management System" of the Chinese Center for Disease Control and Prevention from January 2009 to June 2021. Finally, 8 243 FRS cases with nucleic acid detection results of eight viruses [human influenza virus (HIFV), human respiratory syncytial virus (HRSV), human adenovirus (HAdV), human parainfluenza virus (HPIV), human rhinovirus (HRV), human metapneumovirus (HMPV), human coronavirus (HCoV) and human Boca virus (HBoV)] were included in the study. The χ2 test/Fisher exact probability method was used to analyze the difference of virus detection rate in different age groups, regions and seasons. Results The M (Q1, Q3) age of 8 243 FRS cases was 4 (1, 18) years old, and 56.56% (4 662 cases) were children under 5 years old. Males accounted for 58.1% (4 792 cases) of all cases. All cases were from outpatient/emergency department (2 043 cases) and inpatient department (6 200 cases). The virus detection rates of FRS cases from high to low were HRSV, HIFV, HPIV, HRV, HAdV, HMPV, HCoV and HBoV. Two or more viruses were detected simultaneously in 524 cases, accounting for 15.66% of virus-positive cases. The difference of the virus detection rate in different age groups was statistically significant (all P values<0.05), and the virus detection rate in children<5 years old was higher (49.96%). The positive rate of any virus in south China was higher than that in north China (P<0.001). The virus-positive FRS cases were detected throughout the year. The detection rate of HRSV was higher in autumn and winter. The detection rate of HIFV was higher in winter. The detection rate of HMPV was higher in winter and spring. The detection rates of HPIV, HRV, HCoV and HBoV were higher in summer and autumn, while there was no significant difference in the detection rate of HAdV in different seasons. Compared with 2009-2019, the detection rate of any virus in 2020-2021 decreased from 41.37% to 37.86%. The detection rate of HIFV decreased sharply from 10.62% to 1.37%. The detection rate of HPIV decreased from 8.24% to 5.88%. The detection rate of HRV and HBoV increased from 5.43% and 1.79% to 9.67% and 3.19%, respectively. Conclusion: HRSV and HIFV infections are more common among FRS cases in nine provinces in China from 2009 to 2021, and the epidemiological characteristics of eight common respiratory viruses vary in different age groups, regions and seasons.

[Genotype and genetic characteristics of human respiratory syncytial virus circulating in Quanzhou, 2018-2019].

Objective: To study the prevalence and genetic characteristics of human respiratory syncytial virus (HRSV) in Quanzhou city, from 2018 to 2019. Methods: A total of 141 throat swabs were collected from children patients of lower respiratory tract infection in Quanzhou children Hospital, Fujian Province from November 2018 to May 2019. RT-PCR was used to amplify the 3 'end of G gene HRSV. Sequencer 5.0 and MEGA5.05 softwares were used for sequence editing, phylogenetic tree construction and genotyping analysis. Results: Twenty-five samples were positive for HRSV. Seventeen samples succeeded to obtain the target gene, including 13 of HRSVA and 4 of HRSVB. Two genotypes were identified: ON1 genotype (13 samples, HRSVA) and BA9 genotype (4 samples, HRSVB). Five strains of ON1 genotype sequences were clustered with the ON1 sequences prevalent in Beijing, Changchun and Zhejiang from 2012 to 2015 (cluster1); one strain (FJ19-02) was clustered with the sequences of ON1 genotype circulating in many regions of China from 2012 to 2015 (cluster2); Seven strains were clustered independently (cluster FJ). FJ18-02, FJ19-14 and FJ19-15 of HRSVB were clustered with the BA9 genotype sequences prevalent in Changchun, Jilin Province in 2015, while FJ19-13 was closely related to the BA9 genotype sequences prevalent in Guangzhou and Zhejiang Province in 2013. Both the ON1 and BA9 genotypes showed variations of nucleotide and amino acid in 72 and 60 insertion segments. Amino acid mutation (H266L) only occurred among the sequence of cluster-FJ, and the mutations of H261Q and Q265L only appeared in strain FJ19-13. Conclusion: BA9 and ON1 genotypes were prevalent in Quanzhou city, from 2018 to 2019. Cluster-FJ was a newly discovered independent transmission chain, which may continue to circulate in local Quanzhou area.

[Transthoracic ultrasonographic features of typical high-resolution computed tomography signs of interstitial lung diseases].

Objective: To investigate the accuracy of bedside transthoracic lung ultrasonography (TLU) in different typical high resolution computed tomography (HRCT) signs of interstitial lung diseases (ILDs). Methods: Fifty patients first diagnosed with ILDs were enrolled from January 2016 to December 2018. There were 21 males and 29 females. The mean age was (56±14) years(rang 42-73 years). TLU was performed in inspiration for the characters of A-lines and B-lines as well as pleural at anterior, lateral and dorsal chest walls, respectively. HRCT was selected at three levels according to the upper, middle, and lower lung fields. The range of each level needing to be evaluated corresponded to the TLU scanning field one by one, and recording the signs of HRCT. Early change of ILDs was definite as the HRCT score was no more than 1 and no honeycomb was present. The correlation between A-lines, B-lines, pleural abnormal and HRCT signs was evaluted. Spearman's correlation coefficient was used to evaluate the relationship between B-lines and HRCT score. Results: The sensitivity and specificity of A-lines for HRCT normality were 83.9% and 84.9%, respectively. Coincidence rate was 84.6%. The sensitivity and specificity of B-lines for HRCT abnormality were 84.9% and 83.9%, respectively. Coincidence rate was 84.6%. Interlobular septal thickening shadow had fewer B-lines and narrower interval than other HRCT signs, while the other HRCT signs had no differences in B-lines. And the sensitivity and specificity of B-lines for detection the early change of HRCT in ILDs were 89.5% and 89.2%, respectively. Coincidence rate was 89.3%. A positive correlation was found between the number of B-lines and HRCT scores (R=0.827, P<0.001), and the width of B-lines and HRCT score (R=0.951, P<0.001). Meanwhile, a negative correlation was found between the interval of B-lines and HRCT score (R=-0.831, P<0.001). The sensitivity and specificity of TLU for HRCT pleural abnormality were 100.0% and 90.0%, respectively. Coincidence rate was 93.6%. Conclusions: TLU showed high sensitivity and specificity in finding interstitial changes of the lung. It gives a new view on the diagnostic possibilities of ILDs and may be used to evaluate the severity and the therapeutic effect of treatment. However, TLU could not differentiate HRCT signs of ILDs.

Assessing the Burden of Clostridium difficile Infection in Low- and Middle-Income Countries.

In contrast to the significant resources invested in the diagnosis and prevention of Clostridium difficile infection (CDI) in resource-rich settings, in resource-limited settings patients with community- and hospital-acquired diarrhea may not routinely be tested for CDI. Is CDI actually less frequent or severe in resource-limited settings, or might we be missing an important opportunity to prevent CDI-related morbidity and mortality (and to promote antibiotic stewardship) in these settings? Here, we review the literature to assess the overall burden of CDI in low- and middle-income countries.

[Genetic characterization of varicella zoster virus in Jilin province in 2014, China].

OBJECTIVE: To clarify the genotype of wild-type strains of varicella zoster virus (VZV) in Jilin province in 2014, and to discriminate between v-Oka vaccine strains and wild-type strains. METHODS: Vesicle fluid and throat swab samples were collected from 13 individuals with suspected VZV in Jilin province from January to December 2014. Viral DNA was extracted, the fragments of 15 open reading fragments (ORFs) were amplified by polymerase chain reaction (PCR), and viral genotypes were determined by single nucleotide polymorphisms (SNP). PCR restriction fragment length polymorphism (RFLP) was used to distinguish between wild-type strains and v-Oka vaccine strains. The results were analyzed with MEGA5 software, using the VZV reference strain sequences from GenBank. RESULTS: The 13 suspected samples included 5 males and 8 females, aged 11-27 years (mean: (16.69±5.48) years). Sampling was performed on days 0 to 3 of suspected infection. VZV strains were detected in 8 samples, all belonging to Clade 2. There was a synonymous mutation (T>C) in SNP18082 compared with the v-Oka vaccine strain. Analysis of PCR-RFLPs showed that all 8 positive samples were wild-type strains (PstⅠ(+)BglⅠ(+)SmaⅠ(-)). CONCLUSIONS: The study revealed that the VZV strains circulating in Jilin province in 2014 were wild-type strains belonging to Clade 2.

Polymorphisms of the bovine MC3R gene and their associations with body measurement traits and meat quality traits in Qinchuan cattle.

The melanocortin 3 receptor (MC3R) gene, which belongs to the rhodopsin-like family A of the G protein-coupled receptor family, plays a crucial role in feed efficiency and energy homeostasis. The aim of this study was to examine associations between bovine MC3R gene polymorphisms and body measurement traits (BMTs) and meat quality traits (MQTs). We identified three synonymous mutations (T429C, T537C, and T663C) in exon 1 of the MC3R gene in Chinese Qinchuan beef cattle (N = 271) by sequencing. D' and r(2) values revealed that these three SNPs were in strong linkage disequilibrium (LD) (r(2) > 0.33); the T429C and T537C SNPs were in complete LD (D' = 1 and r(2) = 1). Association analyses revealed that the SNPs were significantly associated with BMTs and MQTs in Qinchuan cattle. Individuals with the wild homozygotic genotypes g.TTTT and g.TT had significantly higher values of chest depth, heart girth, back fat thickness, intramuscular fat content, and loin muscle area than the mutant heterozygotic genotypes g.TCTC and g.TC. These results suggest that the MC3R gene affects MQTs in Qinchuan cattle, and that it may be a good candidate gene for marker-assisted selection.

Tumour-infiltrating inflammation and prognosis in colorectal cancer: systematic review and meta-analysis.

BACKGROUND: The role of tumour-infiltrating inflammation in the prognosis of patients with colorectal cancer (CRC) has not been fully evaluated. The primary objective of our meta-analysis was to determine the impact of tumour-infiltrating inflammation on survival outcomes. METHODS: Ovid MEDLINE and EMBASE were searched to identify studies reporting the prognostic significance of tumour-infiltrating inflammation for patients with CRC. The primary outcome measures were overall survival (OS), cancer-specific survival (CS) and disease-free survival (DFS). RESULTS: A total of 30 studies involving 2988 patients were identified. Studies were subdivided into those considering the associations between CRC survival and generalised tumour inflammatory infiltrate (n=12) and T lymphocyte subsets (n=18). Pooled analyses revealed that high generalised tumour inflammatory infiltrate was associated with good OS (HR, 0.59; 95% CI, 0.48-0.72), CS (HR, 0.40; 95% CI, 0.27-0.61) and DFS (HR, 0.72; 95% CI, 0.57-0.91). Stratification by location and T lymphocyte subset indicated that in the tumour centre, CD3+, CD8+ and FoxP3+ infiltrates were not statistically significant prognostic markers for OS or CS. In the tumour stroma, high CD8+, but not CD3+ or FoxP3+ cell infiltrates indicated increased OS. Furthermore, high CD3+ cell infiltrate was detected at the invasive tumour margin in patients with good OS and DFS; and high CCR7+ infiltrate was also indicated increased OS. CONCLUSION: Overall, high generalised tumour inflammatory infiltrate could be a good prognostic marker for CRC. However, significant heterogeneity and an insufficient number of studies underscore the need for further prospective studies on subsets of T lymphocytes to increase the robustness of the analyses.

Dry environment on the expression of lacrimal gland S100A9, Anxa1, and Clu in rats via proteomics.

AIM: To investigate the underlying mechanism of dry environment (autumn dryness) affecting the lacrimal glands in rats. METHODS: Twenty Sprague-Dawley rats were randomly divided into two groups. The rats were fed in specific pathogen free environment as the control group (n=10), and the rats fed in dry environment as the dryness group (n=10). After 24d, lacrimal glands were collected from the rats. The tissues morphology was observed by hematoxylin-eosin (HE) staining. Tandem mass tags (TMT) quantitative proteomics analysis technology was used to screen the differential expressed proteins of lacrimal glands between the two groups, then bioinformatics analysis was performed. Further, the immunohistochemical (IHC) method was used to verify the target proteins. RESULTS: In dryness group, the lacrimal glands lobule atrophied, the glandular cavities enlarged, the sparse nuclear distribution and scattered inflammatory infiltration between the acinus were observed. The proteomics exhibited that a total of 195 up-regulated and 236 down-regulated differential expressed proteins screened from the lacrimal glands of rats. It was indicated that the biological processes (BP) of differential expressed proteins mainly included cell processes and single BP. The cellular compositions of differential expressed proteins mainly located in cells, organelles. The molecular functions of differential expressed proteins mainly included binding, catalytic activity. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the differential expressed proteins mainly involved lysosome, complement and coagulation cascade, and ribosome pathway. The IHC result verified that the up-regulated expression proteins of Protein S100A9 (S100A9), Annexin A1 (Anxa1), and Clusterin (Clu) in lacrimal glands of rats in dryness group were higher than control group. CONCLUSION: The up-regulated expression proteins of S100A9, Anxa1, and Clu may be the potential mechanisms of dry eye symptoms caused by dry environment. This study provides clues of dry environments causing eye-related diseases for further studies.

Genetically modified pigs: Emerging animal models for hereditary hearing loss.

Hereditary hearing loss (HHL), a genetic disorder that impairs auditory function, significantly affects quality of life and incurs substantial economic losses for society. To investigate the underlying causes of HHL and evaluate therapeutic outcomes, appropriate animal models are necessary. Pigs have been extensively used as valuable large animal models in biomedical research. In this review, we highlight the advantages of pig models in terms of ear anatomy, inner ear morphology, and electrophysiological characteristics, as well as recent advancements in the development of distinct genetically modified porcine models of hearing loss. Additionally, we discuss the prospects, challenges, and recommendations regarding the use pig models in HHL research. Overall, this review provides insights and perspectives for future studies on HHL using porcine models.

Design, Synthesis, and Bioactivity Investigation of Cyclic Lipopeptide Antibiotics Containing Eight to Nine Amino Acids.

The current global issue of antibiotic resistance is serious, and there is an urgent requirement of developing novel antibiotics. Octapeptins have recently regained interest because of their activities against resistant Gram-negative bacteria. We synthesized four natural octapeptins and 33 derivatives with diverse polarity, amphiphilicity, and acid-base properties by solid-phase synthesis and investigated their in vitro antibacterial activity and renal cytotoxicity. We also assessed the structure-activity relationship and structure-toxicity relationship of the cyclic lipopeptide compounds. Some compounds showed increased activity against Gram-negative and/or Gram-positive bacteria, with improved renal cytotoxicity. C-02 showed remarkable in vitro antibacterial activity and low renal cytotoxicity. We found that C-02 showed high antibacterial activity against Escherichia coli in vivo and manifested its effects preliminarily by increasing outer membrane permeability. Therefore, C-02 might be a new antibiotic lead compound with not only high efficacy but also low renal cytotoxicity.

Polymyxin-based fluorescent probes to combat Gram-negative antimicrobial resistance.

Reliable diagnostic approaches especially those targeting critical Gram-negative bacteria are urgently needed for the prevention of antimicrobial resistance. Polymyxin B (PMB) which specifically targets the outer membrane of Gram-negative bacteria is the last-line antibiotic against life-threatening multidrug-resistant Gram-negative bacteria. However, increasing number of studies have reported the spread of PMB-resistant strains. With the aim to specifically detect Gram-negative bacteria and potentially reduce the irrational use of antibiotics, we herein rationally designed two Gram-negative bacteria specific fluorescent probes based on our previous activity-toxicity optimization of PMB. The in vitro probe PMS-Dns showed fast and selective labeling of Gram-negative pathogens in complex biological cultures. Subsequently, we constructed the caged in vivo fluorescent probe PMS-Cy-NO2 by conjugating bacterial nitroreductase (NTR)-activatable positive charged hydrophobic near-infrared (NIR) fluorophore with polymyxin scaffold. Significantly, PMS-Cy-NO2 exhibited excellent Gram-negative bacterial detection capability with the differentiation between Gram-positive and Gram-negative in a mouse skin infection model.

hIMB1636-MMAE, a Novel TROP2-Targeting Antibody-Drug Conjugate Exerting Potent Antitumor Efficacy in Pancreatic Cancer.

Herein, we first prepared a novel anti-TROP2 antibody-drug conjugate (ADC) hIMB1636-MMAE using hIMB1636 antibody chemically coupled to monomethyl auristatin E (MMAE) via a Valine-Citrulline linker and then reported its characteristics and antitumor activity. With a DAR of 3.92, it binds specifically to both recombinant antigen (KD ∼ 0.687 nM) and cancer cells and could be internalized by target cells and selectively kill them with IC50 values at nanomolar/subnanomolar levels by inducing apoptosis and G2/M phase arrest. hIMB1636-MMAE also inhibited cell migration, induced ADCC effects, and had bystander effects. It displayed significant tumor-targeting ability and excellent tumor-suppressive effects in vivo, resulting in 5/8 tumor elimination at 12 mg/kg in the T3M4 xenograft model or complete tumor disappearance at 10 mg/kg in BxPc-3 xenografts in nude mice. Its half-life in mice was about 87 h. These data suggested that hIMB1636-MMAE was a promising candidate for the treatment of pancreatic cancer with TROP2 overexpression.

Synthesis and anti-ovarian cancer effects of benzimidazole-2-substituted pyridine and phenyl propenone derivatives.

Background: Given the benzimidazole derivatives have anti-ovarian cancer effects, the authors aimed to determine whether benzimidazole-2-substituted pyridine and phenyl propenone derivatives exert anti-ovarian cancer activity. Materials & methods: 21 derivatives were synthesized and assayed for their antiproliferative activities. Western blotting in A2780 cells was used to detect the effects of compound A-6 on apoptosis-related proteins. Invasion, migration and apoptosis were assayed in SKOV3 cells treated with A-6. The in vivo activity was also examined. Results: A-6 could inhibit proliferation, invasion and migration and induce apoptosis in SKOV3 cells. Additionally, A-6 had potent inhibitory activity in a xenograft mouse model. Conclusion: A-6 shows potent efficacy in the treatment of ovarian cancer and may be a potential antitumor agent.

The Low-Alkalinity Polymyxin Derivative, AL-6, Shows High Activity Against Multidrug-Resistant Acinetobacter baumannii Clinical Isolates In Vitro and A. baumannii ATCC 19606 In Vivo: Preliminary Analysis of the Antibacterial Mechanism.

Polymyxin B and colistin (polymyxin E) are increasingly used as the last line of therapy for infections caused by multidrug-resistant (MDR) gram-negative pathogens. However, nephrotoxicity is still a limiting factor for the use of polymyxin. Therefore, better tolerated and more effective polymyxin derivatives are urgently needed. In this study, we aimed to evaluate the activity of the low-alkalinity polymyxin derivative, AL-6, against MDR Acinetobacter baumannii (Ab) clinical isolates in vitro and A. baumannii ATCC 19606 in vivo. Additionally, we performed a preliminarily study of the antibacterial mechanism. AL-6 showed much higher activity (0.125-0.25 µg/mL) against MDR A. baumannii clinical isolates than polymyxin E2 (PE2, 0.5-1 µg/mL). AL-6 also showed much higher activity (0.5-256 µg/mL) against polymyxin-resistant strains than PE2 (16-1024 µg/mL). Additionally, AL-6 showed slow resistance against A. baumannii. AL-6 also increased the survival rates of mice by 10% at 48 h compared with PE2 (5 mg/kg). AL-6 could be used at a dose of up to 10 mg/kg, increasing the survival rate to 30% at 72 h after infection. A preliminary study of the antibacterial mechanism showed that AL-6 permeabilized the outer membrane and destroyed cell membrane integrity. Moreover, there was a substantial increase in zeta potential (i.e., less negative) upon AL-6 exposure for A. baumannii. Overall, AL-6 carrying only four positive charges showed high activity against A. baumannii in vitro by disrupting cell membrane integrity. Higher doses of AL-6 could increase survival rates of mice. Thus, AL-6 may have potential applications as a bactericidal agent.

Transport comparison of multiwall carbon nanotubes by contacting outer shell and all shells.

Carbon nanotubes, particularly multiwall carbon nanotubes (MWCNTs) can serve as interconnects in nanoelectronic devices and integrated circuits because of their extremely large current-carrying capacity. Many experimental results about the transport properties of individual MWCNTs by contacting outer shell or all shells have been reported. In this work, a compatible method with integrated circuit manufacturing process was presented to compare the transport property of an individual multiwall carbon nanotube (MWCNT) by contacting outer shell only and all shells successively. First of the Ti/Au electrodes contacting outer shell only were fabricated onto the nanotube through the sequence of electron beam lithography (EBL) patterning, metal deposition and lift-off process. After the characterization of its transport property, focused ion beam (FIB) was used to drill holes through the same nanotube at the as-deposited electrodes. Then new contact to the holes and electrodes were made by ion-induced deposition of tungsten from W(CO)6 precursor gas. The transport results indicated that the new contact to all shells can clear up the intershell resistance and the electrical conductance of the tube can be improved about 8 times compared to that of by contacting outer shell only.

Design, Synthesis, and Bioactivity of Cyclic Lipopeptide Antibiotics with Varied Polarity, Hydrophobicity, and Positive Charge Distribution.

Twenty-three polymyxin analogs with variations at nine amino acid positions were synthesized and assessed for antimicrobial activity and renal cytotoxicity. Compounds M2, 14, S2, and 16 (MIC = 0.125-4 µg/mL) had similar or stronger activities against susceptible and drug-resistant strains of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii compared to polymyxin B (MIC = 1-2 µg/mL). Most synthesized compounds (50% cytotoxic concentration, CC50 ≥ 200 µg/mL) exhibited lower cytotoxicity than polymyxin B (CC50 = 99 ± 6 µg/mL). Polymyxin S2 showed high plasma stability in vitro and strong efficacy in a mouse systemic infection model (ED50 = 0.9 mg/kg) against NDM-1-producing Klebsiella pneumoniae, suggesting that it is a potential candidate for drug development. The activity and cytotoxicity results indicated that the amino acids at positions 2, 3, 6, and 7 might be replaced. Effects on activity and cytotoxicity linked to changes in the number of positively charged amino acids varied among different cyclopeptide skeletons, but the underlying mechanisms are unknown.