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Biofilm formation is an important and ubiquitous mode of growth among bacteria. Central to the evolutionary advantage of biofilm formation is cell-cell and cell-surface adhesion achieved by a variety of factors, some of which are diffusible compounds that may operate as classical public goods-factors that are costly to produce but may benefit other cells. An outstanding question is how diffusible matrix production, in general, can be stable over evolutionary timescales. In this work, using Vibrio cholerae as a model, we show that shared diffusible biofilm matrix proteins are indeed susceptible to cheater exploitation and that the evolutionary stability of producing these matrix components fundamentally depends on biofilm spatial structure, intrinsic sharing mechanisms of these components, and flow conditions in the environment. We further show that exploitation of diffusible adhesion proteins is localized within a well-defined spatial range around cell clusters that produce them. Based on this exploitation range and the spatial distribution of cell clusters, we constructed a model of costly diffusible matrix production and related these length scales to the relatedness coefficient in social evolution theory. Our results show that production of diffusible biofilm matrix components is evolutionarily stable under conditions consistent with natural biofilm habitats and host environments. We expect the mechanisms revealed in this study to be relevant to other secreted factors that operate as cooperative public goods in bacterial communities and the concept of exploitation range and the associated analysis tools to be generally applicable.
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Bactérias , Matriz Extracelular de Substâncias Poliméricas , Evolução Social , Bactérias/crescimento & desenvolvimento , Modelos Biológicos , Vibrio choleraeRESUMO
BACKGROUND: Odronextamab, a CD20×CD3 bispecific antibody that engages cytotoxic T cells to destroy malignant B cells, has demonstrated encouraging activity across multiple subtypes of relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma. PATIENTS AND METHODS: This phase II study (ELM-2; NCT03888105) evaluated odronextamab in patients with R/R follicular lymphoma (FL) after ≥2 lines of systemic therapy. Patients received intravenous odronextamab in 21-day cycles, with step-up dosing in Cycle 1 to help mitigate the risk of cytokine release syndrome (CRS), until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by independent central review. RESULTS: Among 128 patients evaluated, 95% completed Cycle 1, and 85% completed ≥4 cycles. At 20.1 months' efficacy follow-up, ORR was 80.0% and complete response rate was 73.4%. Median duration of complete response was 25.1 months. Median progression-free survival was 20.7 months, and median overall survival was not reached. Discontinuation of odronextamab due to adverse events (AEs) occurred in 16% of patients. The most common treatment-emergent AEs were CRS (56%; grade ≥3 1.7% [1/60] with 0.7/4/20 mg step-up), neutropenia (39%), and pyrexia (38%). CONCLUSIONS: Odronextamab achieved high complete response rates with generally manageable safety in patients with heavily pretreated R/R FL.
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Objective: To investigate pertinent risk factors for postoperative pancreatic fistula(POPF) after robotic-assisted distal pancreatectomy(RDP). Methods: This is a retrospective cohort study. Clinical data of 1 211 patients who underwent various methods of distal pancreatectomy at the Department of General Surgery,Ruijin Hospital,Shanghai Jiaotong University School of Medicine,between January 2021 and December 2023 were retrospectively collected. Among the 1 211 patients,440 cases were in the robot-assisted group(173 males and 267 females),with an age(M(IQR)) of 55(29)years;720 cases were in the open surgery group (390 males and 330 females),with an age of 64(15)years;and 51 cases were in the laparoscopic group(17 males and 34 females),with an age of 56(25)years. These 440 patients who underwent RDP were divided into two cohorts based on the presence of clinically relevant pancreatic fistulas(grades B and C). Univariate and multivariate analysis were performed on 27 factors related to POPF. Univariate analysis methods included independent sample t-test,Mann-Whitney U test,and χ2 test,while multivariate analysis utilized binary logistic regression. Results: After stratification by pathological type,there was no significant difference in the incidence of pancreatic fistula between the robot-assisted group and the open surgery group(benign tumor:χ2=1.200,P=0.952;malignant tumor:χ2=0.391,P=0.532). The surgical duration of the RDP group (Z1=15.113,P1<0.01; Z2=4.232, P2<0.01) was significantly shorter than that of the open surgery and laparoscopic groups,so as the intraoperative blood loss (Z1=12.530,P1<0.01;Z2=2.550,P2=0.032). Postoperative hospital stay in the RDP group was significantly shorter than that in the open surgery group (Z1=10.947, P1<0.01), but not different from that in the laparoscopic group (P2>0.05). All 440 patients underwent successful surgery,of which there was only 1 case who underwent a conversion to open surgery. A total of 104 patients(23.6%) developed clinically relevant pancreatic fistulas,and no perioperative mortality was observed. Univariate analysis revealed that 6 factors were associated with POPF after RDP: gender(χ2=12.048,P=0.001),history of smoking (χ2=6.327,P=0.012),history of alcohol consumption (χ2=17.597,P<0.01),manual pancreas division (χ2=9.839,P=0.002),early elevation of amylase in drainage fluid (Z=5.187,P<0.01),and delayed gastric emptying (χ2=4.485,P=0.034). No statistically significant association with POPF was found for the remaining factors(all P>0.05).The cut-off value for the early amylase level in the drainage fluid was determined to be 7 719.5 IU/ml,with an area under curve of 0.676 determined by receiver operating characteristic curve analysis. Binary logistic regression analysis identified a history of alcohol consumption(P=0.002,95%CI: 0.112 to 0.623), manual pancreas division(P=0.001,95%CI:1.446 to 4.082),early amylase level of drainage fluid ≥7 719.5 IU/ml(P<0.01,95%CI:0.151 to 0.438),and delayed gastric emptying (P=0.020, 95%CI: 1.131 to 4.233) as independent risk factors for POPF of RDP. Conclusion: Patients with pancreatic body and tail tumors who receive RDP therapy are at increased risk of developing a pancreatic fistula if they have a history of alcohol consumption,manual pancreas division,early elevation of amylase in drainage fluid to ≥7 719.5 IU/ml, or delayed gastric emptying.
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Pancreatectomia , Fístula Pancreática , Neoplasias Pancreáticas , Complicações Pós-Operatórias , Procedimentos Cirúrgicos Robóticos , Humanos , Fístula Pancreática/etiologia , Fístula Pancreática/epidemiologia , Masculino , Feminino , Estudos Retrospectivos , Pancreatectomia/métodos , Pancreatectomia/efeitos adversos , Fatores de Risco , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias Pancreáticas/cirurgia , Laparoscopia/métodos , Idoso , AdultoRESUMO
Objective: To preliminarily examine the feasibility and outcome of single-port laparoscopic radical prostatectomy with full-length urethral preservation (FLUP-SPRP). Method: This study was a prospective case series study. A total of 25 patients with prostate cancer who met the enrollment criteria and agreed to this surgical procedure from March 2022 to December 2022 were collected at the Department of Urology, the Second Affiliated Hospital of Nanjing Medical University. The age of the patients was (67.2±7.6) years (range: 61 to 76 years). This novel procedure was performed by an experienced surgeon who performed single hole radical prostatectomy skillfully. Patient urinary control, tumor control, and related surgical complications after surgery were regularly monitored. Postoperative urinary control was evaluated using the daily amount of urine pad, 0 to 1 piece of urine pad was to restore urinary control, and 0 to 1 piece of pad within 24 hours after catheter removal was immediate urinary control. Result: All prodecures were successfully completed without transit to open surgery. The surgical time was (128.4±22.4) minutes (range: 100 to 145 minutes), the intraoperative blood loss was (68.2±13.7) ml (range: 50 to 120 ml). The urethral injury occurred in 4 cases during surgery and was repaired by sutures. The urinary control recovery rates within 24 hours, 1 week, 4 weeks, and 7 weeks after surgery were 80.0%, 84.0%, 92.0% and 100%, respectively. Postoperative large section pathology revealed 1 case with a positive basal margin of the prostate and negative margins of all prostate glands around the urethra. Postoperative complications included urinary tract infection in 3 cases, urodynia in 2 cases, and acute urinary retention in 1 case. MRI follow-up 3 months after surgery showed normal anatomy of the bladder and urethra. The follow-up values of prostate specific antigen at 3 and 6 months after surgery were less than 0.1 µg/L. Conclusions: The preliminary results of this study indicate that the FLUP-SPRP procedure is safe and feasible. The early results of postoperative urinary control and oncology are as expected.
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Laparoscopia , Neoplasias da Próstata , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Uretra/cirurgia , Uretra/patologia , Bexiga Urinária , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Anastomose Cirúrgica/métodos , Prostatectomia/métodos , Laparoscopia/métodosRESUMO
BACKGROUND: Early detection of cancer offers the opportunity to identify candidates when curative treatments are achievable. The THUNDER study (THe UNintrusive Detection of EaRly-stage cancers, NCT04820868) aimed to evaluate the performance of enhanced linear-splinter amplification sequencing, a previously described cell-free DNA (cfDNA) methylation-based technology, in the early detection and localization of six types of cancers in the colorectum, esophagus, liver, lung, ovary, and pancreas. PATIENTS AND METHODS: A customized panel of 161 984 CpG sites was constructed and validated by public and in-house (cancer: n = 249; non-cancer: n = 288) methylome data, respectively. The cfDNA samples from 1693 participants (cancer: n = 735; non-cancer: n = 958) were retrospectively collected to train and validate two multi-cancer detection blood test (MCDBT-1/2) models for different clinical scenarios. The models were validated on a prospective and independent cohort of age-matched 1010 participants (cancer: n = 505; non-cancer: n = 505). Simulation using the cancer incidence in China was applied to infer stage shift and survival benefits to demonstrate the potential utility of the models in the real world. RESULTS: MCDBT-1 yielded a sensitivity of 69.1% (64.8%-73.3%), a specificity of 98.9% (97.6%-99.7%), and tissue origin accuracy of 83.2% (78.7%-87.1%) in the independent validation set. For early-stage (I-III) patients, the sensitivity of MCDBT-1 was 59.8% (54.4%-65.0%). In the real-world simulation, MCDBT-1 achieved a sensitivity of 70.6% in detecting the six cancers, thus decreasing late-stage incidence by 38.7%-46.4%, and increasing 5-year survival rate by 33.1%-40.4%, respectively. In parallel, MCDBT-2 was generated at a slightly low specificity of 95.1% (92.8%-96.9%) but a higher sensitivity of 75.1% (71.9%-79.8%) than MCDBT-1 for populations at relatively high risk of cancers, and also had ideal performance. CONCLUSION: In this large-scale clinical validation study, MCDBT-1/2 models showed high sensitivity, specificity, and accuracy of predicted origin in detecting six types of cancers.
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Ácidos Nucleicos Livres , Neoplasias , Feminino , Humanos , Metilação de DNA , Estudos Prospectivos , Estudos Retrospectivos , Ácidos Nucleicos Livres/genética , Neoplasias/diagnóstico , Neoplasias/genética , Biomarcadores Tumorais/genética , Detecção Precoce de CâncerRESUMO
Symmetry plays a central role in conventional and topological phases of matter, making the ability to optically drive symmetry changes a critical step in developing future technologies that rely on such control. Topological materials, like topological semimetals, are particularly sensitive to a breaking or restoring of time-reversal and crystalline symmetries, which affect both bulk and surface electronic states. While previous studies have focused on controlling symmetry via coupling to the crystal lattice, we demonstrate here an all-electronic mechanism based on photocurrent generation. Using second harmonic generation spectroscopy as a sensitive probe of symmetry changes, we observe an ultrafast breaking of time-reversal and spatial symmetries following femtosecond optical excitation in the prototypical type-I Weyl semimetal TaAs. Our results show that optically driven photocurrents can be tailored to explicitly break electronic symmetry in a generic fashion, opening up the possibility of driving phase transitions between symmetry-protected states on ultrafast timescales.
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With the discovery that 48% of cholera infections in rural Bangladesh villages could be prevented by simple filtration of unpurified waters and the detection of Vibrio cholerae aggregates in stools from cholera patients it was realized V. cholerae biofilms had a central function in cholera pathogenesis. We are currently in the seventh cholera pandemic, caused by O1 serotypes of the El Tor biotypes strains, which initiated in 1961. It is estimated that V. cholerae annually causes millions of infections and over 100,000 deaths. Given the continued emergence of cholera in areas that lack access to clean water, such as Haiti after the 2010 earthquake or the ongoing Yemen civil war, increasing our understanding of cholera disease remains a worldwide public health priority. The surveillance and treatment of cholera is also affected as the world is impacted by the COVID-19 pandemic, raising significant concerns in Africa. In addition to the importance of biofilm formation in its life cycle, V. cholerae has become a key model system for understanding bacterial signal transduction networks that regulate biofilm formation and discovering fundamental principles about bacterial surface attachment and biofilm maturation. This chapter will highlight recent insights into V. cholerae biofilms including their structure, ecological role in environmental survival and infection, regulatory systems that control them, and biomechanical insights into the nature of V. cholerae biofilms.
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COVID-19 , Cólera , Vibrio cholerae , Humanos , Cólera/epidemiologia , Cólera/microbiologia , Pandemias , BiofilmesRESUMO
The prognosis for pancreatic cancer is extremely poor. To improve the prognosis of pancreatic cancer, it is urgently needed to improve early detection to advance treatment. And basically, it is also necessary to emphasise basic research to find novel therapies. By promoting the disease-centered multidisciplinary team model, researchers should achieve high-quality closed-loop process management of the entire life cycle which consists of prevention, screening, diagnosis, treatment, rehabilitation,and follow-up, with the objective of establishing a standard clinical process to improve the outcome in essence. This article summarized the progress of pancreatic cancer at different stages of the whole cycle management recently and shared the experience of pancreatic cancer treatment from the author's team in the past ten years.
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Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , Pâncreas , Prognóstico , Neoplasias PancreáticasRESUMO
Using anteroposterior (AP) hip radiograph, we measured several indexes to investigate the association with bone mineral density (BMD) before THA and found a highly effective index to predict femoral BMD. This technique is helpful for both patients and clinicians to identify potential candidates with low BMD to whom DXA examination is particularly recommended. INTRODUCTION: The purpose of the study is to identify patients with low bone mineral density (BMD) prior to total hip arthroplasty with the help of AP hip radiographs. METHODS: Indexes on AP hip radiographs and T-scores from DXA examination of the lumbar spine and the affected hip were acquired from patients before THA. Indexes measured on AP hip radiographs including the canal calcar ratio (CCR), canal flare index (CFI), morphological cortical index (MCI), canal bone ratio (CBR), and canal bone area ratio (CBAR). The relevance between indexes and the T-score of femora was evaluated by correlation analysis, and the diagnostic value of indexes for osteopenia was examined by receiver operating characteristic (ROC) curves. RESULTS: A total of 81 patients were included. The average value of CBR-7, CBR-10, and CBAR (7-10) were highly related to the T-score of femora (r = - 0.592, r = - 0.634, and r = - 0.631, respectively, p < 0.0001). Results of the intra- and interobserver variation assessment was excellent. CBR-7, CBR-10, and CBAR (7-10) were significantly different between the non-osteopenia and osteopenia groups (p < 0.0001). CBR-10 had the biggest area under curve (AUC), means the great diagnostic value for osteopenia in the proximal femora (AUC = 0.821, cutoff value = 0.3805). CONCLUSION: The canal bone ratio at 10 × 10-2 m under the level of the lesser trochanter proved to be a great indicator of femoral osteopenia. Trial registration Chinese Clinical Trail Registry, ChiCTR2000041016. Registered 16 December 2020-Retrospectively registered, http://www.chictr.org.cn/listbycreater.aspx .
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Artroplastia de Quadril , Doenças Ósseas Metabólicas , Absorciometria de Fóton , Artroplastia de Quadril/efeitos adversos , Densidade Óssea , Doenças Ósseas Metabólicas/diagnóstico por imagem , Humanos , Vértebras Lombares/diagnóstico por imagemRESUMO
Objective: To explore the diagnostic value of different serological markers and the correlation with disease phenotype in inflammatory bowel disease (IBD). Methods: The clinical data of 445 IBD patients in Peking Union Medical College Hospital from June 2010 to December 2020 were retrospectively collected, including 223 cases of ulcerative colitis (UC) [111 males, 112 females, with a median age of 46(20,79) years] and 222 cases of Crohn's disease (CD) [147 males, 75 females, with a median age of 39 (19, 72) years]. The positive rates of serum anti-neutrophil cytoplasmic antibodies (ANCA), anti-Saccharomyces cerevisiae antibodies (ASCA), goblet cell autoantibodies (GAB) and pancreatic autoantibodies (PAB) in the two groups were analyzed. The sensitivity, specificity, positive predictive value and negative predictive value of UC and CD were calculated. Logistic regression was performed to analyze the relationship between different combinations of antibodies and disease phenotype. Results: The positive rates of ASCA and PAB in CD patients were 34.7% (77/222) and 38.3% (85/222), respectively, which were higher than those in UC patients [10.3% (23/223) and 4.5% (10/223), P<0.001]. The positive rate of ANCA in UC patients was 50.2% (112/223), which was higher than that in CD patients [5.4% (12/222), P<0.001]. The positive rates of serum GAB in CD and UC patients were 21.6% (48/222) and 28.3% (63/223), respectively, with no significant difference (P=0.760). In patients with CD, the sensitivity of mono-marker ASCA (+), dual-marker ASCA (+) ANCA (-), quadruple-marker ASCA (+) ANCA (-) PAB (+) GAB (-) in diagnosing CD was 34.7%, 32.9%, 20.7%, the specificity was 89.7%, 95.5%, 100.0%, the positive predictive value was 77.0%, 90.1%, 100.0%, and the negative predictive value was 58.0%, 58.7%, 55.9%, respectively. In patients with UC, the sensitivity of mono-marker ANCA (+), dual-marker ANCA (+) ASCA (-), quadruple-marker ANCA (+) ASCA (-) PAB (-) GAB (+) in diagnosing UC was 50.2%, 40.4%, 24.2%, the specificity was 94.6%, 95.5%, 100.0%, the positive predictive value was 90.3%, 90.0%, 100.0%, and the negative predictive value was 65.4%, 61.4%, 56.8%, respectively. Mono-marker ASCA (+) (OR=3.39, 95%CI: 1.59-7.21), dual-marker ASCA (+) ANCA (-) (OR=2.87, 95%CI: 1.34-6.14), triple-marker ASCA (+) ANCA (-) GAB (-) (OR=3.09, 95%CI: 1.31-7.31) and quadruple-marker ASCA (+) ANCA (-) PAB (+) GAB (-) (OR=3.15, 95%CI: 1.56-8.03) were associated with stenosis and/or penetrating type CD. The mono-marker ANCA (+) (OR=2.69, 95%CI: 1.42-5.12) and dual-marker ANCA (+) ASCA (-) (OR=2.11, 95%CI: 1.03-4.16) were associated with extensive colonic lesions in UC. Conclusion: Based on ASCA or ANCA, the combination with PAB or GAB, is conducive to IBD diagnosis, and is associated with stenosis and/or penetrating type of CD and extensive type of UC.
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Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Masculino , Feminino , Humanos , Anticorpos Anticitoplasma de Neutrófilos , Estudos Retrospectivos , Constrição Patológica , Colite Ulcerativa/diagnóstico , Doença de Crohn/diagnóstico , Doenças Inflamatórias Intestinais/diagnóstico , Autoanticorpos , Fenótipo , BiomarcadoresRESUMO
Enhancement of light extraction efficiency (LEE) of AlGaN-based deep-ultraviolet (DUV) light emitting diodes (LEDs) has been attempted by adopting Ag-nanodots/Al reflective electrodes on a highly transparent complex p-type layer. By thinning the p-GaN to several nm, highly DUV transparent p-type layer is achieved, making it meaningful for the application of reflective electrodes composed of Ag-nanodots and Al film to allow most light emitted upward to be reflected back to the sapphire side. By this approach, the maximum light output power and external quantum efficiency of the DUV-LEDs with optimized Ag nanodots/Al electrodes are severally increased by 52% and 58%, respectively, compared to those with traditional Ni/Au electrodes when the current is below 200â mA.
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AIM: To evaluate whether portable chest radiography (CXR) scores are associated with coronavirus disease 2019 (COVID-19) status and various clinical outcomes. MATERIALS AND METHODS: This retrospective study included 500 initial CXR from COVID-19-suspected patients. Each CXR was scored based on geographic extent and degree of opacity as indicators of disease severity. COVID-19 status and clinical outcomes including intensive care unit (ICU) admission, mechanical ventilation, mortality, length of hospitalisation, and duration on ventilator were collected. Multivariable logistic regression analysis was performed to evaluate the relationship between CXR scores and COVID-19 status, CXR scores and clinical outcomes, adjusted for code status, age, gender and co-morbidities. RESULTS: The interclass correlation coefficients amongst raters were 0.94 and 0.90 for the extent score and opacity score, respectively. CXR scores were significantly (p < 0.01) associated with COVID-19 positivity (odd ratio [OR] = 1.49; 95% confidence interval [CI]: 1.27 - 1.75 for extent score and OR = 1.75; 95% CI: 1.42 - 2.15 for opacity score), ICU admission (OR = 1.19; 95% CI: 1.09 - 1.31 for extent score and OR = 1.26; 95% CI: 1.10 - 1.44 for opacity score), and invasive mechanical ventilation (OR = 1.22; 95% CI: 1.11 - 1.35 for geographic score and OR = 1.21; 95% CI: 1.05 - 1.38 for opacity score). CXR scores were not significantly different between survivors and non-survivors after adjusting for code status (p>0.05). CXR scores were not associated with length of hospitalisation or duration on ventilation (p>0.05). CONCLUSIONS: Initial CXR scores have prognostic value and are associated with COVID-19 positivity, ICU admission, and mechanical ventilation.
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COVID-19/diagnóstico por imagem , COVID-19/terapia , Cuidados Críticos , Pulmão/diagnóstico por imagem , Respiração Artificial , Idoso , Feminino , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Radiografia , Radiografia Torácica , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de Doença , TriagemRESUMO
Liquid crystals are widely known for their facile responses to external fields, which forms a basis of the modern information display technology. However, switching of molecular alignment field configurations typically involves topologically trivial structures, although singular line and point defects often appear as short-lived transient states. Here, we demonstrate electric and magnetic switching of nonsingular solitonic structures in chiral nematic and ferromagnetic liquid crystals. These topological soliton structures are characterized by Hopf indices, integers corresponding to the numbers of times that closed-loop-like spatial regions (dubbed "preimages") of two different single orientations of rod-like molecules or magnetization are linked with each other. We show that both dielectric and ferromagnetic response of the studied material systems allow for stabilizing a host of topological solitons with different Hopf indices. The field transformations during such switching are continuous when Hopf indices remain unchanged, even when involving transformations of preimages, but discontinuous otherwise.
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Data indicate that dietary thiamine supplementation can partly alleviate rumen epithelium inflammation and barrier function in goats fed a high-concentrate diet. The current work aimed to explore whether thiamine promotes rumen epithelium development by regulating carbohydrate metabolism during a long period of feeding high levels of concentrate. For the experiment, 24 female Boer goats (35.62 ± 2.4 kg of body weight) in parity 1 or 2 were allocated to 3 groups (8 goats per replicate) receiving a low-concentrate diet (concentrate:forage 30:70), a high-concentrate diet (HC; concentrate:forage 70:30), or a high-concentrate diet (concentrate:forage 70:30) supplemented with 200 mg of thiamine/kg of dry matter intake (HCT; concentrate:forage 70:30). On the last day of 12 wk, rumen fluid and blood samples were collected to measure ruminal parameters, endotoxin lipopolysaccharide, and blood inflammatory cytokines. Goats were slaughtered to collect ruminal tissue to determine differential metabolites, enzyme activities, and gene expression. Liquid chromatography-tandem mass spectrometry analysis revealed that the HCT group had significantly increased concentrations of d-glucose 6-phosphate, d-fructose 6-phosphate, glyceraldehyde 3-phosphate, thiamine pyrophosphate, oxaloacetate, acetyl-CoA, succinyl-CoA, sedoheptulose 7-phosphate, ribose 5-phosphate, and NADPH compared with the HC group. The pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and transketolase enzyme activities in the rumen epithelium of the HCT group were higher than those in the HC group. The plasma total antioxidant capacity values for the HCT group were greater than those for the HC group. The rumen epithelium ATP content in the HCT group was higher than that in the HC group. Compared with the HCT group, the HC group had a lower mRNA abundance of CCND1, CCNA2, CDK2, CDK4, CDK6, BCL2, PI3K, and AKT1. Taken together, the results suggest that dietary thiamine supplementation could ameliorate disorders in the tricarboxylic acid cycle and the pentose phosphate pathway induced by a long-term high-concentrate diet and could promote rumen epithelial growth.
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Doenças das Cabras , Doenças Metabólicas , Ração Animal/análise , Animais , Dieta/veterinária , Feminino , Cabras , Concentração de Íons de Hidrogênio , Doenças Metabólicas/veterinária , Gravidez , Rúmen , TiaminaRESUMO
ABSTRACT: Objective To study the metabolic transformation pathways of 4F-MDMB-BUTINACA in vivo by establishing zebrafish models. Methods Six adult zebrafish were randomly divided into blank control group and experimental group, with three fish in each group. After the zebrafish in the experimental group were exposed to 1 µg/mL 4F-MDMB-BUTINACA for 24 h, they were transferred to clean water and cleaned three times, then pretreated for instrumental analysis. The zebrafish in blank control group were not exposed to 4F-MDMB-BUTINACA. Mass spectrometry and structural analysis of 4F-MDMB-BUTINACA and its metabolites were conducted by liquid chromatography-high resolution mass spectrometry and Mass Frontier software. Results A total of twenty-six metabolites of 4F-MDMB-BUTINACA were identified in zebrafish, including eighteen phase â metabolites and eight phase â ¡ metabolites. The main metabolic pathways of phase â metabolites of 4F-MDMB-BUTINACA in zebrafish were ester hydrolysis, N-dealkylation, oxidative defluorination and hydroxylation, while the main metabolic pathway of phase â ¡ metabolites was glucuronidation. Conclusion Metabolite Md24 ï¼ester hydrolysisï¼ and Md25 ï¼ester hydrolysis combined with dehydrogenationï¼ would be recommended to be potentially good biomarkers for abuse of 4F-MDMB-BUTINACA.
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Canabinoides , Drogas Ilícitas , Animais , Cromatografia Líquida , Microssomos Hepáticos/química , Peixe-ZebraRESUMO
ABSTRACT: Objective To establish a detection method for common new psychoactive substances of synthetic cannabinoids in hair with ultra-high performance liquid chromatography-tandem mass spectrometry ï¼UPLC-MS/MSï¼. Methods In the 1 mL of internal standard methanol solution, 20 mg hair was added. After cryogenic grinding and ultrasonic extraction, the extract was separated by ACQUITY UPLC HSS T3 column ï¼100 mm×2.1 mm, 1.8 µmï¼. The mobile phase A was aqueous solution that composed of 20 mmol/L ammonium acetate, 0.1% formic acid, and 5% acetonitrile. The mobile phase B was acetonitrile. Electrospray ionization source in positive ion mode was used for data acquisition in multi-reaction monitoring ï¼MRMï¼ mode. Results The seven common new psychoactive substances of synthetic cannabinoids in hair had a good linear relationship within their respective linear ranges ï¼r>0.99ï¼, the limits of detection were 0.5-2 pg/mg, the limits of quantification were 1-5 pg/mg, the intra-day and inter-day precisions were 0.1%-12.6%, the intra-day and inter-day accuracies were 89.2%-110.7%, the recovery rates were 52.3%-93.3%, and the matrix effects were 19.1%-95.2%. Conclusion The established method has a simple sample preparation process and high sensitivity. It is suitable for qualitative and quantitative analysis of common new psychoactive substances of synthetic cannabinoids in hair.
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Canabinoides , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , CabeloRESUMO
Three-dimensional topological solitons attract a great deal of interest in fields ranging from particle physics to cosmology, but remain experimentally elusive in solid-state magnets. Here we numerically predict magnetic heliknotons, an embodiment of such nonzero-Hopf-index solitons localized in all spatial dimensions while embedded in a helical or conical background of chiral magnets. We describe conditions under which heliknotons emerge as metastable or ground-state localized nonsingular structures with fascinating knots of magnetization field in widely studied materials. We demonstrate magnetic control of three-dimensional spatial positions of such solitons, as well as show how they interact to form moleculelike clusters and possibly even crystalline phases comprising three-dimensional lattices of such solitons with both orientational and positional order. Finally, we discuss both fundamental importance and potential technological utility of magnetic heliknotons.
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Near-ultraviolet micro-LEDs with different diameters were fabricated on GaN substrates. The electroluminescence and the light output power-current density and current density-voltage relationships were measured. A saturated current density of 358â kA/cm2 was achieved with a 20â µm LED. The ideality factor curves showed steps and peaks when the injection current density was increased from 20 to 150â kA/cm2 and an abnormal efficiency increase. The transport and recombination processes of micro-LEDs at high injection current densities were simulated, and the many-body effect and phase space filling in the integrated quantum drift-diffusion model were considered. Serious current crowding was observed above 100â kA/cm2, even for the 20â µm LED.
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Carrier transport in AlGaN-based deep ultraviolet (DUV) light emitting diodes (LEDs) with the wavelength of 273 nm has been investigated by introducing polarization modulated electron blocking layer (EBL) that adopts an Al composition and thickness graded multiple quantum barriers (MQB) structure. The experimental result shows that the maximum light output power and external quantum efficiency for the proposed structure at the current of 250 mA are 9.6 mW and 1.03% respectively, severally increasing by 405% and 249% compared to traditional one, meanwhile, the efficiency droop at 250 mA is also dramatically reduced from 42.2% to 16.6%. Further simulation analysis indicates that this graded MQB-EBL enhances the potential barrier height for electrons and meanwhile reduces that for holes, hence effectively suppresses the electron leakage, and at the same time significantly improves the hole injection efficiency. As a result, the whole performance of the LED with the proposed MQB-EBL is dramatically improved.
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The emergence and rapid spread of insecticide resistance in several mosquito species has become a significant obstacle in management of mosquito-borne diseases, including deltamethrin resistance in Culex pipiens pallens. Previous study identified a major deltamethrin resistance quantitative trait locus (DR-6) that alone explained 62% of the genetic variance. In this study, the marker L4B1.102 and L4B1.175 associated with the DR-6 were characterized. We searched for potential candidate genes in the flank region of two markers in the genome sequence and showed that a cluster of CYP6 cytochrome P450 genes (CYP6BB4, CYP6BB3, CYP6CC2, CYP6P14, CYP6BZ2, CYP6AA9, CYP6AA8, CYP6AA7) was in the vicinity of DR-6. Significant differences in the expression of these P450s in the larval and adult stages were identified in the resistant strains compared with the susceptible strain. For CYP6AA9 and CYP6BB4, the correlation analysis showed a highly positive correlation between relative gene expression quantification and the resistance level in different strains. Knockdown of CYP6BB4 increased the sensitivity of mosquitoes to deltamethrin. We identified that the deltamethrin resistance was in a cluster of CYP6 genes in C. pipiens pallens, and CYP6BB4 may play a significant role in the development of deltamethrin resistance.