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OBJECTIVES: The genus Streptococcus contains species of important zoonotic pathogens such as those that cause bovine mastitis. Unfortunately, many Streptococcus species have developed antibiotic resistance. Phage lysins are considered promising alternatives to antibiotics because it is difficult for bacteria to develop lysin resistance. However, there remains a lack of phage lysin resources for the treatment of streptococci-induced mastitis. METHODS: We identified the prophage lysin Lys0859 from the genome of the Streptococcus suis SS0859 strain. Lys0859 was subsequently characterized to determine its host range, MIC, bactericidal activity in milk, and ability to clear biofilms in vitro. Finally, to determine the effects of Lys0859 on the treatment of both bovine mastitis and S. suis infection in vivo, we established models of Streptococcus agalactiae ATCC 13813-induced mastitis and S. suis serotype 2 SC19 systemic infection. RESULTS: Our results demonstrate that Lys0859 possesses broad-spectrum lytic activity against Streptococcus and Staphylococcus species isolated from animals with bovine mastitis and 15 serotypes of S. suis isolated from swine. Intramammary and intramuscular injection of Lys0859 reduced the number of bacteria in mammary tissue by 3.75 and 1.45 logs compared with the PBS group, respectively. Furthermore, 100 µg/mouse of Lys0859 administered intraperitoneally at 1 h post-infection protected 83.3% (5/6) of mice from a lethal dose of S. suis infection. CONCLUSIONS: Overall, our results enhance the understanding and development of new strategies to combat both streptococci-induced mastitis and S. suis infection.
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Bacteriófagos , Mastite Bovina , Infecções Estreptocócicas , Fagos de Streptococcus , Streptococcus suis , Feminino , Bovinos , Animais , Suínos , Camundongos , Humanos , Prófagos/genética , Mastite Bovina/tratamento farmacológico , Antibacterianos/farmacologia , Infecções Estreptocócicas/microbiologiaRESUMO
INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a serious lung disease with a high mortality rate. Baoyuan decoction (BYD), a classic medicinal food homology recipe, has anti-apoptotic effects, enhances immune function, and alleviates fibrosis, suggesting that it may be a potential therapeutic drug for IPF. OBJECTIVES: We aimed to identify the main active ingredients of BYD, determine the basis of its efficacy, prove its anti-IPF effects, and explore the mechanisms underlying its anti-IPF effects. MATERIALS AND METHODS: In this study, the active components of BYD were detected and analysed by ultra-high-performance liquid chromatography coupled with hybrid quadrupole Orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap-MS). A network pharmacology analysis was performed to determine the potential targets and relevant pathways of BYD in treating IPF. Western blotting and quantitative real-time polymerase chain reaction (qPCR) were conducted to verify the efficacy of BYD against IPF. Finally, molecular docking and qPCR were performed to identify the central targets of BYD. RESULTS: A total of 39 components of BYD were identified. After performing the network pharmacology analysis, 35 active components and eight presumptive targets of BYD were found to play a central role in its anti-IPF effects. The molecular docking results indicated that most of the active components of BYD exhibited good binding activity with these eight central target proteins. In addition, the expression of collagen, α-SMA, and these eight targets in human pulmonary fibroblast (HPF) cells was suppressed from treatment with BYD. CONCLUSION: This study determined the efficacy of BYD against IPF and clarified its multiple-target and multiple-pathway mechanisms. Furthermore, the study also provides a new method for exploring the chemical and pharmacological bases of other traditional Chinese medicine (TCM).
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Medicamentos de Ervas Chinesas , Fibrose Pulmonar Idiopática , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Simulação de Acoplamento Molecular , Farmacologia em RedeRESUMO
Shiga toxin-producing Escherichia coli (STEC) strains are important zoonotic foodborne pathogens, causing diarrhea, hemorrhagic colitis, and life-threatening hemolytic uremic syndrome (HUS) in humans. However, antibiotic treatment of STEC infection is associated with an increased risk of HUS. Therefore, there is an urgent need for early and effective therapeutic strategies. Here, we isolated lytic T7-like STEC phage PHB19 and identified a novel O91-specific polysaccharide depolymerase (Dep6) in the C terminus of the PHB19 tailspike protein. Dep6 exhibited strong hydrolase activity across wide ranges of pH (pH 4 to 8) and temperature (20 to 60°C) and degraded polysaccharides on the surface of STEC strain HB10. In addition, both Dep6 and PHB19 degraded biofilms formed by STEC strain HB10. In a mouse STEC infection model, delayed Dep6 treatment (3 h postinfection) resulted in only 33% survival, compared with 83% survival when mice were treated simultaneously with infection. In comparison, pretreatment with Dep6 led to 100% survival compared with that of the control group. Surprisingly, a single PHB19 treatment resulted in 100% survival in all three treatment protocols. Moreover, a significant reduction in the levels of proinflammatory cytokines was observed at 24 h postinfection in Dep6- or PHB19-treated mice. These results demonstrated that Dep6 or PHB19 might be used as a potential therapeutic agent to prevent STEC infection.IMPORTANCE Shiga toxin-producing Escherichia coli (STEC) is an important foodborne pathogen worldwide. The Shiga-like toxin causes diarrhea, hemorrhagic colitis, and life-threatening hemolytic uremic syndrome (HUS) in humans. Although antibiotic therapy is still used for STEC infections, this approach may increase the risk of HUS. Phages or phage-derived depolymerases have been used to treat bacterial infections in animals and humans, as in the case of the "San Diego patient" treated with a phage cocktail. Here, we showed that phage PHB19 and its O91-specific polysaccharide depolymerase Dep6 degraded STEC biofilms and stripped the lipopolysaccharide (LPS) from STEC strain HB10, which was subsequently killed by serum complement in vitro In a mouse model, PHB19 and Dep6 protected against STEC infection and caused a significant reduction in the levels of proinflammatory cytokines. This study reports the use of an O91-specific polysaccharide depolymerase for the treatment of STEC infection in mice.
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Colífagos/fisiologia , Glicosídeo Hidrolases/genética , Escherichia coli Shiga Toxigênica/virologia , Proteínas Virais/genética , Colífagos/genética , Glicosídeo Hidrolases/metabolismo , Proteínas Virais/metabolismoRESUMO
The correlated photon technique makes it possible to achieve a radiation calibration processing without chain transferring. The study of the spectral radiation character and time correlation of the photon is of great significance for broad-band radiometric calibration. To absolutely calibrate quantum efficiency of photoelectric detector, it is necessary to extend calibration band from single band to more bands. According to the phase-matching condition of the spontaneous parametric down-conversion, non-collinear angle formula of correlated photon in the crystal is derived. The distribution of the photon spectrum is simulated. Meanwhile, the phase-matching angle of the crystal is optimized. The photon generated by the spontaneous parameters down-conversion has a broad spectral distribution and the correlated photon wavelength is corresponding to its emission angle. Based on the result of the simulation, the experimental measurement system of the spectral distribution and time-correlation of the correlated photon is established. The spectral distribution, the time-correlation and the polarization properties of the four pair photon were measured by using this system. The experimental results show that, (1) the spectral distribution of the measurements is 633~808 nm, where the maximum spectral distribution measurement bias is 1.51 mm. The experiment result is highly consistent with theoretical ones; (2) the correlation time of four pairs correlated photon is measured, during which "three coincidence-peaks" is observed and the minimum correlation time was 0.32 ns; (3) single photon count rate along with coincidence count rate of correlated photon vary with the polarization direction of the pump as sine function. The experimental result is shown that the correlated photon pairs are ranging from the visible to near infrared band distribution, and that the spectrum has time-correlation and polarization characteristic. The research result is firstly reported at home and abroad, and the results are promising for the application of the photoelectric detector in the multi-band radiometric calibration.
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Background: The effectiveness and safety of using Brucea javanica oil (BJO) in combination with Transarterial Chemoembolization (TACE) for liver cancer treatment are subjects of debate. This study aims to assess the comparative effectiveness and safety of BJO-assisted TACE versus TACE alone and quantifies the differences between these two treatment methods. Methods: A systematic search was conducted in multiple databases including PubMed, Cochrane, CNKI, and Wanfang, until 1 July 2023. Meta-analysis was conducted, and the results were presented as mean difference (MD), risk ratio (RR), and 95% confidence intervals (CI). Results: The search yielded 11 RCTs, with a combined sample size of 1054 patients. Meta-analysis revealed that BJO-assisted TACE exhibited superior outcomes compared to standalone TACE. Specific data revealed that BJO-assisted TACE improves clinical benefit rate by 22% [RR = 1.22, 95% CI (1.15, 1.30)], increases the number of people with improved quality of life by 32%, resulting in an average score improvement of 9.53 points [RR = 1.32, 95% CI (1.22, 1.43); MD = 9.53, 95% CI (6.95, 12.10)]. Furthermore, AFP improvement rate improved significantly by approximately 134% [RR = 2.34, 95% CI (1.58, 3.46)], accompanied by notable improvements in liver function indicators, with an average reduction of 27.19 U/L in AST [MD = -27.19, 95% CI (-40.36, -14.02)], 20.77 U/L in ALT [MD = -20.77, 95% CI (-39.46, -2.08)], 12.17 µmol/L in TBIL [MD = -12.17, 95% CI (-19.38, -4.97)], and a decrease of 43.72 pg/mL in VEGF [MD = -43.72, 95% CI (-63.29, -24.15)]. Most importantly, there was a 29% reduction in the occurrence of adverse reactions [RR = 0.71, 95% CI (0.60, 0.84)]. Conclusion: These findings indicate that BJO-assisted TACE may be considered as a potentially beneficial treatment option for liver cancer patients when compared to standalone TACE. It appears to contribute to improved treatment outcomes, enhanced quality of life, and potentially reduced adverse reactions, suggesting it warrants further investigation as a promising approach for liver cancer treatment. Systematic Review Registration: identifier CRD42023428948.
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The nacre has excellent impact resistance performance, and it is attracting attention in the field of aerospace composite research. Inspired by the layered structure from nacre, semi-cylindrical nacre-like composite shells of brittle silicon carbide ceramic (SiC) and aluminum (AA5083-H116) were established. Two types of tablet arrangements (regular hexagonal and Voronoi polygons) of the composites were designed, and the same size of ceramic and aluminum shell were established for the impact resistance analyzed numerically. In order to better compare the resistance performance of the four types of structures under different impact velocity, the following parameters were analyzed including energy variation, damage characteristic, bullet residual velocity, and semi-cylindrical shell displacement. The results show that the semi-cylindrical ceramic shells have higher rigidity and ballistic limit, but the severe vibration after impact causes penetrating cracks, and the whole structure failure occurred eventually. The nacre-like composites have higher ballistic limits than semi-cylindrical aluminum shells, and the impact of bullets only causes local failure. In the same conditions, the impact resistance of regular hexagons is better than Voronoi polygons. The research analyzes the resistance characteristic of nacre-like composites and single materials, and provides a reference for the design of nacre-like structures.
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ETHNOPHARMACOLOGICAL RELEVANCE: Pulmonary fibrosis (PF), a lethal lung disease, can lead to structural destruction of the alveoli until death. Sparganii Rhizoma (SR), primarily distributed in East Asia, has been used clinically for hundreds of years against organ fibrosis and inflammation. AIM OF THE STUDY: We intended to verify the effect of SR alleviate PF and further explore mechanisms. METHODS: Murine model of PF was established by endotracheal infusion of bleomycin. We detected the anti-PF effect of SR through lung coefficient, hydroxyproline content, lung function and pathological staining. Then, we used Western Blot and RT-PCR to verify the mechanism. In vitro experiments, MRC-5 and BEAS-2B were induced to phenotypic transformation by TGF-ß1 and then RT-PCR, WB and IF were conducted to verify the effect of SR. RESULTS: SR significantly reduced BLM-induced PF in mice, improved lung function, slowed the degree of lung tissue lesions, and reduced collagen deposition. SR alleviated PF by inhibiting fibroblasts differentiation and epithelial-mesenchymal transition. In vivo studies explored the mechanism and found that it was related to TGF-ß1/Smad2/3 pathway. CONCLUSIONS: Our research proved SR could effectively treat PF, providing a fresh idea and approach for the treatment of PF with traditional Chinese medicine.
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Fibrose Pulmonar , Camundongos , Animais , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Transição Epitelial-Mesenquimal , Pulmão , Bleomicina , Fibroblastos/metabolismoRESUMO
Most of the current mainstream 6D pose estimation methods use template or voting-based methods. Such methods are usually multi-stage or have multiple assumptions and post-correction, which will cause a certain degree of information redundancy and increase the computational cost, their real-time detection performance is poor. We point out that traditional path aggregation networks introduce new errors, therefore, we propose a loss function: MagicCubeLoss, a portable module: MagicCubeNet, and the corresponding 6D pose estimation model: MagicCubePose. MagicCubePose has good expansion performance and can build more efficient models for different calculation power and scenarios. Experiments show that our model has good real-time detection performance and the highest ADD(-S) accuracy.
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Diabetes mellitus has become a major public health issue globally, putting an enormous burden on global health systems and people. Among all diseased groups, a considerable part of patients are elderly, while their clinical features, pathogenic processes, and medication regimens are different from patients of other ages. Despite the availability of multiple therapies and techniques, there are still numerous elderly diabetes patients suffering from poor blood glucose control, severe complications, and drug adverse effects, which negatively affect the quality of life in their golden years. Traditional Chinese Medicine (TCM) has been widely used in the treatment of diabetes for several decades, and its relevant clinical practice has confirmed that it has a satisfactory effect on alleviating clinical symptoms and mitigating the progression of complications. Chinese herbal medicine and its active components were used widely with obvious clinical advantages by multiple targets and signaling pathways. However, due to the particular features of elderly diabetes, few studies were conducted to explore Traditional Chinese Medicine intervention on elderly diabetic patients. This study reviews the research on clinical features, pathogenic processes, treatment principles, and TCM treatments, hoping to provide fresh perspectives on the prevention and management strategies for elderly diabetes.
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Salmonella is an important zoonotic pathogen that not only endangers food safety and human health, but also causes considerable economic losses to the poultry industry. Therefore, it is essential to establish a rapid, sensitive, and specific diagnostic method for the early detection of Salmonella infection in poultry. In this study, we developed a novel enzyme-linked immunosorbent assay (ELISA) for the detection of anti-Salmonella antibodies using a recombinant SifA protein. Amino acid sequence comparison revealed that SifA is a relatively conserved secretory protein across Salmonella serotypes. Therefore, we hypothesized that SifA can serve as a detection antigen for diagnostic testing. The SifA protein was expressed in Escherichia coli and used as a coating antigen to establish an SifA-ELISA. Control sera from specific-pathogen-free (SPF) chickens infected with Salmonella or several other non-Salmonella pathogens were then tested using the SifA-ELISA. Specificity testing demonstrated that the SifA-ELISA could detect antibodies against 3 different serotypes of Salmonella, whereas antibodies against other non-Salmonella pathogens could not be detected. Compared to the SifA-ELISA, the Salmonella plate agglutination test (PAT) failed to detect antibodies in serum samples from chickens infected with Salmonella Typhimurium. This result suggests that our SifA-ELISA may be better than PAT at detecting Salmonella infection. Comparing clinical sera, we observed a similar rate of Salmonella positivity between SifA-ELISA and PAT (92.6%). In addition, anti-SifA antibodies were continuously detected during Salmonella infection of SPF chickens, demonstrating that SifA-ELISA could consistently detect high levels of antibodies for at least 8 wk. Furthermore, the intra-assay and interassay coefficients of variation (CV) of the SifA-ELISA were below 10%, which is considered acceptable. In summary, the SifA-ELISA established here is a promising and reliable method for detection of anti-Salmonella antibodies in poultry and may contribute to the early diagnosis of Salmonella infection.
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Doenças das Aves Domésticas , Salmonelose Animal , Animais , Humanos , Aves Domésticas , Galinhas , Anticorpos Antibacterianos , Proteínas Recombinantes , Salmonella typhimurium , Ensaio de Imunoadsorção Enzimática/veterinária , Ensaio de Imunoadsorção Enzimática/métodos , Salmonelose Animal/diagnóstico , Doenças das Aves Domésticas/diagnóstico , Sensibilidade e EspecificidadeRESUMO
Salmonella and pathogenic Escherichia coli are important foodborne pathogens. Phages are being recognized as potential antibacterial agents to control foodborne pathogens. In the current study, a polyvalent broad-spectrum phage, GSP044, was isolated from pig farm sewage. It can simultaneously lyse many different serotypes of Salmonella and E. coli, exhibiting a broad host range. Using S. Enteritidis SE006 as the host bacterium, phage GSP044 was further characterized. GSP044 has a short latent period (10 min), high stability at different temperatures and pH, and good tolerance to chloroform. Genome sequencing analysis revealed that GSP044 has a double-stranded DNA (dsDNA) genome consisting of 110,563 bp with G + C content of 39%, and phylogenetic analysis of the terminase large subunit confirmed that GSP044 belonged to the Demerecviridae family, Epseptimavirus genus. In addition, the genomic sequence did not contain any lysogenicity-related, virulence-related, or antibiotic resistance-related genes. Analysis of phage-targeted host receptors revealed that the outer membrane protein (OMP) BtuB was identified as a required receptor for phage infection of host bacteria. The initial application capability of phage GSP044 was assessed using S. Enteritidis SE006. Phage GSP044 could effectively reduce biofilm formation and degrade the mature biofilm in vitro. Moreover, GSP044 significantly decreased the viable counts of artificially contaminated S. Enteritidis in chicken feed and drinking water. In vivo tests, a mouse model of intestinal infection demonstrated that phage GSP044 was able to reduce the number of colonized S. Enteritidis in the intestine. These results suggest that phage GSP044 may be a promising candidate biologic agent for controlling Salmonella infections.
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Bacteriófagos , Camundongos , Animais , Suínos , Bacteriófagos/genética , Escherichia coli/genética , Filogenia , Genoma Viral , Salmonella/genética , Especificidade de HospedeiroRESUMO
BACKGROUND: Gemcitabine (GEM)-based chemotherapy regimens is widely used in bladder cancer (BC) patients. However, GEM resistance may occur and result in treatment failure and disease progression. A disintegrin and metalloprotease 12 (ADAM12) plays a critical role in many cancers. However, the role of ADAM12 in GEM resistance of BC remains unclear. METHODS: We analyzed the relationship between ADAM12 expression and tumor characteristics using the data downloaded from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database. Then, we established GEM resistant BC cell lines and used quantitative real-time PCR, western blot, cell counting kit-8, immunohistochemistry, and xenograft mouse model to investigate the role of ADAM12 in GEM resistance. RESULTS: In general, ADAM12 was found to be upregulated in GEM resistant BC cells. ADAM12 knockdown increased the chemosensitivity of BC cells. We further proved that ADAM12 could promote GEM resistance by activating the epidermal growth factor receptor (EGFR) signaling pathway in BC. Furthermore, the epithelial-mesenchymal transition (EMT) phenotype was observed in GEM resistant BC cells. ADAM12 induced EMT process and promotes tumor progression in BC. CONCLUSION: Our findings suggested that ADAM12 was a key gene for GEM resistance and positively correlated with malignancy of BC. It might serve as a novel and valuable therapeutic target for BC.
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Antineoplásicos , Resistencia a Medicamentos Antineoplásicos , Transição Epitelial-Mesenquimal , Gencitabina , Neoplasias da Bexiga Urinária , Animais , Humanos , Camundongos , Proteína ADAM12/genética , Proteína ADAM12/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Resistencia a Medicamentos Antineoplásicos/fisiologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Transição Epitelial-Mesenquimal/fisiologia , Receptores ErbB/genética , Receptores ErbB/metabolismo , Gencitabina/farmacologia , Gencitabina/uso terapêutico , Regulação Neoplásica da Expressão Gênica , Transdução de Sinais/genética , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologiaRESUMO
Salmonella is a food-borne zoonotic pathogen that threatens food safety and public health security. Temperate phages can influence bacterial virulence and phenotype and play an important role in bacterial evolution. However, most studies on Salmonella temperate phages focus on prophage induced by bacteria, with few reports on Salmonella temperate phages isolated in the environment. Moreover, whether temperate phages drive bacterial virulence and biofilm formation in food and animal models remains unknown. In this study, Salmonella temperate phage vB_Sal_PHB48 was isolated from sewage. TEM and phylogenetic analysis indicated that phage PHB48 belongs to the Myoviridae family. Additionally, Salmonella Typhimurium integrating PHB48 was screened and designated as Sal013+. Whole genome sequencing revealed that the integration site was specific and we confirmed that the integration of PHB48 did not change the O-antigen and coding sequences of Sal013. Our in vitro and in vivo studies showed that the integration of PHB48 could significantly enhance the virulence and biofilm formation of S. Typhimurium. More importantly, the integration of PHB48 significantly improved the colonization and contamination ability of bacteria in food samples. In conclusion, we isolated Salmonella temperate phage directly from the environment and systematically clarified that PHB48 enhanced the virulence and biofilm-forming ability of Salmonella. In addition, we found that PHB48 increased the colonization and contamination ability of Salmonella in food samples. These results indicated that the highly pathogenic Salmonella induced by temperate phage was more harmful to food matrices and public health security. Our results could enhance the understanding of the evolutionary relationship between bacteriophages and bacteria, and raise public awareness of large-scale outbreaks resulting from Salmonella virulence enhancement in food industry.
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Bacteriófagos , Fagos de Salmonella , Animais , Salmonella typhimurium/genética , Virulência , Filogenia , Fagos de Salmonella/genética , BiofilmesRESUMO
Systemic therapy for muscle-invasive bladder cancer (BC) remains dominated by cisplatin-based chemotherapy. However, resistance to cisplatin therapy greatly limits long-term survival. Resistance to cisplatin-based chemotherapy still needs to be addressed. In this study, we established three cisplatin-resistant BC cell lines by multiple cisplatin pulse treatments. Interestingly, after exposure to cisplatin, all cisplatin-resistant cell lines showed lower reactive oxygen species (ROS) levels than the corresponding parental cell lines. Using proteomic analysis, we identified 35 proteins that were upregulated in cisplatin-resistant BC cells. By knocking down eleven of these genes, we found that after CAB39 knockdown, BC cisplatin-resistant cells were more sensitive to cisplatin. Overexpression of CAB39 had the opposite effect. Then, the knockdown of six genes downstream of CAB39 revealed that CAB39 promoted cisplatin resistance in BC through LKB1. Moreover, a key cause of cisplatin-induced cell death is damage to mitochondria and increased ROS levels. In our study, cisplatin-resistant cells exhibited higher autophagic flux and healthier mitochondrial status after cisplatin exposure. We demonstrated that the CAB39-LKB1-AMPK-LC3 pathway plays a critical role in enhancing autophagy to maintain the health of mitochondria and reduce ROS levels. In addition, the autophagy inhibitor chloroquine (CQ) can significantly enhance the killing effect of cisplatin on BC cells. Compared with gemcitabine plus cisplatin (GC), GC plus CQ significantly reduced tumor burden in vivo. In conclusion, our study shows that CAB39 counteracts the killing of cisplatin by enhancing the autophagy of BC cells to damaged mitochondria and other organelles to alleviate the damage of cells caused by harmful substances such as ROS.
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Cisplatino , Resistencia a Medicamentos Antineoplásicos , Neoplasias da Bexiga Urinária , Humanos , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Apoptose , Autofagia , Linhagem Celular Tumoral , Cloroquina/farmacologia , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Proteômica , Espécies Reativas de Oxigênio/metabolismo , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologiaRESUMO
Although the bacterial composition of boar ejaculate has been extensively studied, the bacterial composition of extended boar semen is often overlooked, despite the potential risks these microorganisms may pose to the long-term preservation of extended boar semen at 15-17°C. In this study, we characterized the bacterial community composition of extended semen and discovered that Pseudomonas spp. was the dominant flora. The dominant strains were further isolated and identified as a potential new species in the Pseudomonas fluorescens group and named GXZC strain, which had adverse effects on sperm quality and was better adapted to growth at 17°C. Antimicrobial susceptibility testing showed that the GXZC strain was resistant to all commonly used veterinary antibiotics. Whole-genome sequencing (WGS) and genome annotation revealed the large genetic structure and function [7,253,751 base pairs and 6,790 coding sequences (CDSs)]. Comparative genomic analysis with the closest type strains showed that the GXZC strain predicted more diversity of intrinsic and acquired resistance genes to multi-antimicrobial agents. Taken together, our study highlights a problem associated with the long-term storage of extended boar semen caused by a P. fluorescens group strain with unique biological characteristics. It is essential to develop a new antibacterial solution for the long-term preservation of boar semen.
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Within urban green spaces, spontaneous groundcovers, as potential alternatives for traditional lawns, have garnered attention due to their ecological adaptability. However, little attention has been paid to whether spontaneous groundcovers can serve as suitable replacements for lawns in terms of the aesthetic values and human preferences for each. Based on questionnaires accompanied by photo elicitation, this study explored the perceptions of and preferences for seven kinds of lawns and six kinds of spontaneous groundcovers in China. The effects of social backgrounds on people's perceptions of and preferences for ground covers were also analyzed. The results indicated a general equivalence in preferences for the lawn and spontaneous groundcover. The Taraxacum mongolicum - Cynodon dactylon - Conyza canadensis community was significantly preferred most among all of the selected ground covers. Spontaneous groundcovers were regarded as more natural, wild, variable, and species-richer compared to lawns, while lawns were perceived as better kept than spontaneous groundcovers. Ground covers were preferred which were perceived to have high ecological aesthetic value and low wildness. Industry and attention to herbaceous plants mostly affected human perceptions and preferences among the social background factors, and gender, age, education level, and occupation also had significant effects. The results thus provide the support for the application of spontaneous groundcovers in moderately developed cities, but such application should consider the comprehensive development of ecological aesthetic value and the applicability of different groups of residents.
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Background: Dry eye disease is a common ocular surface disease affecting tens of millions of people worldwide. It is characterized by an unstable tear film and increasing prevalence. Different commercial formulations of cyclosporine A for dry eye have been approved, however, it is still unclear whether the differences in formulations of these products will make a difference in clinical efficacy and safety. Methods: Randomized controlled trials of commercial cyclosporine A formulation for dry eye disease were searched in Pubmed, EMBASE, Scopus, and Cochrane controlled trials registries and Web of Science from inception till 1 December 2021. Independent literature screening, data extraction, quality evaluation, and the study in line with quality standards were analyzed by using Stata16.0 software. The study is registered with PROSPERO under the number CRD42022301423. Code and data for this study is publicly available (https://github.com/DongYangGao/Dongyang.github.io.git). Results: 21 randomized clinical trials with a total of 4,107 participants were included in this study. Restasis® (OR-4.82, 95% CI-6.18 to 3.45, SUCRA 77.2%) was the most effective commercial formulation for reducing OSDI, Zirun® (SUCRA 73.9%) performed better in improving Schirmer's test. TJ Cyporin® (SUCRA 65.3%) ranked first in terms of improving tear film break-up time. For treatment-emergent adverse events incidence, Clacier® was close to placebo. The risk of reporting bias is considered low. Conclusion: In the comparison of outcomes included in this study, the optimal order of various commercial cyclosporine A formulations is different, so it is difficult to select the optimal formula. Appropriate commercial formulations should be selected according to patients' conditions in clinical practice.
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The mechanical behavior of buried HDPE double-wall corrugated pipes is mainly affected by the material and the structure of the pipe wall. Here we studied a peculiar material that added fly ash (FA) in high density polyethylene (HDPE) to develop composites. We have conducted research on FA/HDPE composites with different mix proportions. When 5% compatibilizer was added to the 10% FA masterbatch/HDPE composite, the Young's Modulus of FA/HDPE composite was higher. This paper mainly studies the mechanical behavior of the structure of pipe walls for materials with this proportion of the ingredients. The mechanical behavior of double-wall corrugated pipes with different ratios of interior and exterior wall thicknesses is studied by keeping the sum of the interior and exterior wall thicknesses unchanged. Pipes with six different ratios of interior and exterior wall thicknesses are simulated; the results show that the strain of crest and liner gradually decreased and the valley strain gradually increased with the increase of the exterior wall thickness. By comparing inner and outer wall thickness ratios from 0.67 to 2.33, it is found that the structural performance and economic advantage for the double-wall corrugated pipes is best when the thickness ratio of the interior wall and the exterior wall is controlled to be from 1.3 to 1.8. This paper expounds the deformation mechanism of double-wall corrugated pipes from the perspective of mechanical behavior and structural characteristics, and provides a reference for material selection and structural design of double-wall corrugated pipes.
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The rapid emergence of phage-resistant bacterial mutants is a major challenge for phage therapy. Phage cocktails have been considered one approach to mitigate this issue. However, the synergistic effect of randomly selected phages in the cocktails is ambiguous. Here, we rationally designed a phage cocktail consisting of four phages that utilize the lipopolysaccharide (LPS) O antigen, the LPS outer core, the LPS inner core, and the outer membrane proteins BtuB and TolC on the Salmonella enterica serovar Enteritidis cell surface as receptors. We demonstrated that the four-phage cocktail could significantly delay the emergence of phage-resistant bacterial mutants compared to the single phage. To investigate the fitness costs associated with phage resistance, we characterized a total of 80 bacterial mutants resistant to a single phage or the four-phage cocktail. We observed that mutants resistant to the four-phage cocktail were more sensitive to several antibiotics than the single-phage-resistant mutants. In addition, all mutants resistant to the four-phage cocktail had significantly reduced virulence compared to wild-type strains. Our mouse model of Salmonella Enteritidis infection also indicated that the four-phage cocktail exhibited an enhanced therapeutic effect. Together, our work demonstrates an efficient strategy to design phage cocktails by combining phages with different bacterial receptors, which can steer the evolution of phage-resistant strains toward clinically exploitable phenotypes. IMPORTANCE The selection pressure of phage promotes bacterial mutation, which results in a fitness cost. Such fitness trade-offs are related to the host receptor of the phage; therefore, we can utilize knowledge of bacterial receptors used by phages as a criterion for designing phage cocktails. Here, we evaluated the efficacy of a phage cocktail made up of phages that target four different receptors on Salmonella Enteritidis through in vivo and in vitro experiments. Importantly, we found that pressure from phage cocktails with different receptors can drive phage-resistant bacterial mutants to evolve in a direction that entails more severe fitness costs, resulting in reduced virulence and increased susceptibility to antibiotics. These findings suggest that phage cocktail therapy using combinations of phages targeting different important receptors (e.g., LPS or the efflux pump AcrAB-TolC) on the host surface can steer the host bacteria toward more detrimental surface mutations than single-phage therapy, resulting in more favorable therapeutic outcomes.
Assuntos
Bacteriófagos , Infecções por Salmonella , Camundongos , Animais , Salmonella enteritidis , Bacteriófagos/genética , Lipopolissacarídeos/metabolismo , Virulência , Antígenos O , Antibacterianos/farmacologia , Proteínas de MembranaRESUMO
Asthma, characterized by the continuous inflammatory response caused by a variety of immune cells, is one of the most common chronic respiratory diseases worldwide. Relevant clinical trials proved that the traditional Chinese medicine formula Guizhi Decoction (GZD) had multitarget and multichannel functions, which might be an effective drug for asthma. However, the effective ingredients and mechanisms of GZD against asthma are still unclear. Therefore, network pharmacology, molecular docking, and cell experiments were performed to explore the antiasthma effects and potential mechanisms of GZD. First, we applied the TCMSP database and literature to obtain the bioactivated ingredients in GZD. SwissTargetPrediction, TCMSP, GeneCards, OMIM, PharmGkb, TTD, DrugBank, and STRING database were used to get core genes. In addition, the key pathways were analyzed by the DAVID database. Molecular docking was used to predict whether the important components could act on the core target proteins directly. Finally, qPCR was carried out to verify the network pharmacology results and the possible mechanisms of GZD in the treatment of asthma. We collected 134 active ingredients in GZD, 959 drug targets, and 3223 disease targets. 431 intersection genes were screened for subsequent analysis. Through GO and KEGG analyses, enriched pathways related to inflammation and immune regulation were presented. Through the qPCR method to verify the role of essential genes, we found that GZD had an excellent anti-inflammatory effect. Direct or indirect inhibition of MAPK and NF-κB pathways might be one of the crucial mechanisms of GZD against asthma. GZD might be a promising potential drug for the treatment of asthma. This article provided a reference for the clinical application of GZD.