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OBJECTIVE: Multiple palmoplantar warts, caused by human papillomavirus (HPV) infection, were investigated for clinical efficacy using cantharidin, retinoic acid cream, and salicylic acid cream. METHODS: A total of 110 patients with multiple palmoplantar warts were enrolled. The experimental group (54 cases) received a 1:1:1 combination (CRS) of 0.25% cantharidin, 0.1% retinoic acid cream, and 5% salicylic acid, applied with pressurized encapsulation for 8 h every night, three times per week. The control group (56 cases) underwent conventional liquid nitrogen freezing. Monthly follow-ups assessed cure rate, effective rate, dermatological life quality index (DLQI), visual analog scale (VAS), and cost, with evaluations conducted after 3 months. RESULTS: The treatment group exhibited a cure rate of 85.19% and a total effective rate of 96.30%, surpassing the control group with rates of 39.29% and 51.79%, respectively (p < 0.05). The treatment group's DLQI score (1.84 ± 1.06) was significantly lower than the control group's score (6.04 ± 1.78) (p = 0.0005). Additionally, the treatment group's VAS score (1.84 ± 1.06) was notably lower than the control group's score (8.56 ± 1.07) (p < 0.0001). The treatment group's total cost (43.20 ± 2.85) was markedly lower than the control group's cost (206.38 ± 90.81), with a statistically significant difference (p < 0.0001). CONCLUSION: The combination of cantharidin, retinoic acid cream, and salicylic acid with local encapsulation is a safe, effective, economical, and convenient treatment method for multiple palmoplantar warts, exhibiting few side effects and showing promise.
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Ácido Salicílico , Verrugas , Humanos , Ácido Salicílico/efeitos adversos , Cantaridina/efeitos adversos , Tretinoína/uso terapêutico , Verrugas/tratamento farmacológico , Resultado do TratamentoRESUMO
BACKGROUND: There have been some shifts in the frequency and distribution of biopsy-proven renal diseases in China over recent years. The aim of the study was to investigate the changing spectrum of renal diseases from the view of kidney biopsy data in a single center of China. METHODS AND RESULTS: A total of 10,996 cases of native renal biopsies from patients aged ≥15 years old in Huashan Hospital, Fudan University, between 2008 and 2018 were analyzed retrospectively. The results showed that primary glomerular nephropathy (PGN) remained the most common biopsy-proven renal disease (69.42% of total), with IgA nephropathy (IgAN) accounting for 44.40% of PGN, membranous nephropathy (MN) for 28.55%, minimal change disease (MCD) for 13.26% and focal segmental glomerulosclerosis (FSGS) for 8.00%. During the study period, the proportion of MN in PGN appeared an increasing tendency, while that of IgAN and MCD remained stable and that of FSGS showed a decline. Secondary glomerular nephropathy (SGN) constituted 21.54% of total cases, among which the leading two diseases were lupus nephritis (LN) and Henoch-Schonlein purpura nephritis (HSN) which accounted for 41.08% and 19.11% respectively. CONCLUSIONS: The 11-year retrospective study revealed that PGN was the predominant histologic diagnosis among patients undergoing renal biopsy and the most frequent type of PGN remained to be IgAN, followed by MN which increased dramatically.
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Glomerulonefrite por IGA , Glomerulonefrite Membranosa , Glomerulosclerose Segmentar e Focal , Rim , Nefrose Lipoide , Humanos , China/epidemiologia , Masculino , Estudos Retrospectivos , Adulto , Feminino , Pessoa de Meia-Idade , Biópsia/estatística & dados numéricos , Glomerulonefrite Membranosa/patologia , Glomerulonefrite Membranosa/epidemiologia , Glomerulonefrite por IGA/patologia , Glomerulonefrite por IGA/epidemiologia , Glomerulosclerose Segmentar e Focal/patologia , Glomerulosclerose Segmentar e Focal/epidemiologia , Adulto Jovem , Nefrose Lipoide/patologia , Nefrose Lipoide/epidemiologia , Rim/patologia , Adolescente , Nefrite Lúpica/patologia , Nefrite Lúpica/epidemiologia , Idoso , Vasculite por IgA/patologia , Vasculite por IgA/epidemiologia , Vasculite por IgA/diagnóstico , Glomerulonefrite/patologia , Glomerulonefrite/epidemiologia , Nefropatias/patologia , Nefropatias/epidemiologia , Nefropatias/diagnósticoRESUMO
Many studies have shown that circRNAs and miRNAs play important roles in many different life processes. However, the function of circRNAs in spermatogenesis remains unknown. Here, we aimed to explore the mechanisms whereby circRNA-miRNAs-mRNAs regulate abnormal m6A methylation in GC-1spg spermatogonia. We first reduced m6A methylation in GC-1spg whole cells after knocking down the m6A methyltransferase enzyme, METTL3. Then, we performed circRNA- and miRNA-seq on GC-1spg cells with low m6A methylation and identified 48 and 50 differentially expressed circRNAs and miRNAs, respectively. We also predicted the targets of the differentially expressed miRNAs by using Miranda software and further constructed the differentially expressed circRNA-differentially expressed miRNA-mRNA ceRNA network. GO analysis was performed on the differentially expressed circRNAs and miRNA-targeted mRNAs, and an interaction network between the proteins of interest was constructed using Cytoscape. The final GO analysis showed that the target mRNAs were involved in sperm formation. Therefore, a PPI network was subsequently constructed and 2 hub genes (H2afx and Dnmt3a) were identified. In this study, we constructed a ceRNA network and explored the regulatory roles of circRNAs and miRNAs in the pathogenesis of abnormal spermatogenesis caused by low levels of methylated m6A. Also, we identified two pivotal genes that may be key factors in infertility caused by abnormal m6A methylation. This may provide some ideas for the treatment of infertility resulting from abnormal spermatogenesis.
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Infertilidade , MicroRNAs , Masculino , Humanos , Metilação , RNA Circular/genética , Sêmen , MicroRNAs/genética , RNA Mensageiro/genética , Espermatogênese/genética , MetiltransferasesRESUMO
The formation of skeletal muscle is a complex process that is coordinated by many regulatory factors, such as myogenic factors and noncoding RNAs. Numerous studies have proved that circRNA is an indispensable part of muscle development. However, little is known about circRNAs in bovine myogenesis. In this study, we discovered a novel circRNA, circ2388, formed by reverse splicing of the fourth and fifth exons of the MYL1 gene. The expression of circ2388 was different between fetal and adult cattle muscle. This circRNA is 99% homologous between cattle and buffalo and is localized in the cytoplasm. Thoroughly, we proved that circ2388 had no effect on cattle and buffalo myoblast proliferation but promotes myoblast differentiation and myotube fusion. Furthermore, circ2388 in vivo stimulated skeletal muscle regeneration in mouse muscle injury model. Taken together, our findings suggest that circ2388 promotes myoblast differentiation and promotes the recovery and regeneration of damaged muscles.
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Mioblastos , RNA Circular , Camundongos , Animais , Bovinos , Mioblastos/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Búfalos , Proliferação de Células/genética , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/lesões , Desenvolvimento Muscular/genética , Diferenciação CelularRESUMO
AIMS: To investigate glycaemic variability (GV) patterns in patients with type 1 diabetes (T1D), type 2 diabetes (T2D), and latent autoimmune diabetes in adults (LADA). MATERIALS AND METHODS: A total of 842 subjects (510 T1D, 105 LADA, 227 T2D) were enrolled and underwent 1 week of continuous glucose monitoring (CGM). Clinical characteristics and CGM parameters were compared among T1D, LADA, and T2D. LADA patients were divided into two subgroups based on glutamic acid decarboxylase autoantibody titres (≥180 U/mL [LADA-1], <180 U/mL [LADA-2]) and compared. The C-peptide cut-offs for predicting a coefficient of variation (CV) of glucose ≥36% and a time in range (TIR) > 70% were determined using receiver operating characteristic analysis. RESULTS: Twenty-seven patients (9 T1D, 18 T2D) were excluded due to insufficient CGM data. Sex, diabetes duration and HbA1c were comparable among the three groups. Fasting and 2-h postprandial C-peptide (FCP, 2hCP) increased sequentially across T1D, LADA, and T2D. T1D and LADA patients had comparable TIR and GV, whereas those with T2D had much higher TIR and lower GV (p < 0.001). The GV of LADA-1 was close to that of T1D, while the GV of LADA-2 was close to that of T2D. CP exhibited the strongest negative correlation with GV. The cut-offs of FCP/2hCP for predicting a CV ≥ 36% and TIR >70% were 121.6/243.1 and 128.9/252.8 pmol/L, respectively. CONCLUSIONS: GV presented a continuous spectrum across T1D, LADA-1, LADA-2, and T2D. More frequent glucose monitoring is suggested for patients with impaired insulin secretion. CLINICAL TRAIL REGISTRATION: Chinese Clinical Trial Registration (ChiCTR) website approved by WHO; http://www.chictr.org.cn/ - ChiCTR2200065036.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Ilhotas Pancreáticas , Diabetes Autoimune Latente em Adultos , Adulto , Humanos , Glicemia/análise , Automonitorização da Glicemia , Peptídeo C , Estudos TransversaisRESUMO
Thermal compensation control can correct errors caused by the thermal deformation of phased array antenna (PAA) panels. Thermal deformation of the panel is needed to calculate the compensation value. While the PAA is working, thermal deformation is unconditional to measure, but predicting it by temperature is feasible. However, thermal deformation is also affected by other factors, such as the structural shape, assembly method, and material parameters, and it is difficult to measure these parameters of PAA because of the complex structure. In contrast, the measurement method of the temperature and thermal deformation of the PAA in the laboratory is much easier. Therefore, a comprehensive influence parameters (CIPs)-finite element method (FEM) method was proposed in this study, it can extract the influence of above parameters on thermal deformation from temperature and thermal deformation measurement data and build a thermal deformation prediction model. Experiments have verified that the CIPs-FEM can greatly reduce the difficulty of thermal deformation modeling and have a high prediction accuracy.
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OBJECTIVES: Patients with classical type 1 diabetes mellitus (T1DM) require lifelong dependence on exogenous insulin therapy due to pancreatic beta-cell destruction and absolute insulin deficiency. T1DM accounts for about 90% of children with diabetes in China, with a rapid increase in incidence and a younger-age trend. Epidemiological studies have shown that the overall glycated haemoglobin (HbA1c) and compliance rate are low in Chinese children with T1DM. Optimal glucose control is the key for diabetes treatment, and maintaining blood glucose within the target range can prevent or delay chronic vascular complications in patients with T1DM. Therefore, this study aims to investigate the glycemic control of children with T1DM from Hunan and Henan Province with flash glucose monitoring system (FGMS), and to explore factors associated with glycemic variability. METHODS: A total of 215 children with T1DM under 14 years old were enrolled continuously in 16 hospitals from August 2017 to August 2020. All subjects wore a FGMS device to collect glucose data. Correlation of HbA1c, duration of diabetes, or glucose scan rates with glycemic variability was analyzed. Glucose variability was compared according to the duration of diabetes, HbA1c, glucose scan rates and insulin schema. RESULTS: HbA1c and duration of diabetes were positively correlated with mean blood glucose, standard deviation of glucose, mean amplitude of glucose excursions (MAGE), and coefficient of variation (CV) of glucose (all P<0.01). The glucose scan rates during FGMS wearing was significantly positively correlated with time in range (TIR) (P=0.001) and negatively correlated with MAGE and mean duration of hypoglycemia (all P<0.01). Children with duration ≤1 year had lower time below range (TBR) and MAGE when compared with those with duration >1 year (all P<0.05). TIR and TBR in patients with HbA1c ≤7.5% were higher (TIR: 65% vs 45%, TBR: 5% vs 4%, P<0.05), MAGE was lower (7.0 mmol/L vs 9.4 mmol/L, P<0.001) than those in HbA1c >7.5% group. Compared to the multiple daily insulin injections group, TIR was higher (60% vs 52%, P=0.006), MAGE was lower (P=0.006) in the continuous subcutaneous insulin infusion group. HbA1c was lower in the high scan rates (≥14 times/d) group (7.4% vs 8.0%, P=0.046), TIR was significantly higher (58% vs 47%, P<0.001), and MAGE was lower (P<0.001) than those in the low scan rate (<14 times/d) group. CONCLUSIONS: The overall glycemic control of T1DM patients under 14 years old in Hunan and Henan Province is under a high risk of hypoglycemia and great glycemic variability. Shorter duration of diabetes, targeted HbA1c, higher glucose scan rates, and CSII are associated with less glycemic variability.
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Automonitorização da Glicemia , Diabetes Mellitus Tipo 1 , Hipoglicemia , Adolescente , Glicemia , Criança , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Glucose , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemia/diagnóstico , Hipoglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêuticoRESUMO
OBJECTIVE: The objective of this study was to evaluate the image quality of monoenergetic images (MEIs (+)) acquired from dual-energy computed tomography with low-concentration and low-flow-rate contrast media for the arterial supply to the nipple-areola complex (NAC) in breast cancer compared with conventional computed tomography angiography (CTA). METHODS: We enrolled 25 patients (MEI (+)300 group, 300 mg/mL and 2.5 mL/s of contrast media) and 23 patients (CTA370 group, 370 mg/mL and 3.5 mL/s of contrast media) for assessing NAC blood supply angiography. The image quality of the 2 groups was evaluated objectively and subjectively. RESULTS: The 40 keV MEI (+)300 demonstrated higher attenuation and contrast-to-noise ratio than CTA370 group (P < 0.001). The subjective image quality and visualization of the arteries were comparable between 2 groups. CONCLUSIONS: The 40 keV MEI (+)300 acquired from dual-energy computed tomography can achieve comparable image quality of arterial supply to NAC with low-concentration and low-flow-rate contrast media in breast cancer compared with CTA370.
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Neoplasias da Mama/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Intensificação de Imagem Radiográfica/métodos , Imagem Radiográfica a Partir de Emissão de Duplo Fóton/métodos , Tomografia Computadorizada por Raios X/métodos , Mama/irrigação sanguínea , Mama/diagnóstico por imagem , Angiografia por Tomografia Computadorizada/métodos , Meios de Contraste , Feminino , Humanos , Pessoa de Meia-Idade , Mamilos/irrigação sanguínea , Mamilos/diagnóstico por imagem , Estudos Prospectivos , Reprodutibilidade dos Testes , Razão Sinal-RuídoRESUMO
Aflatoxin B1 (AFB1), a food contaminant derived from Aspergillus fungi, has been reported to cause hepatic immunotoxicity via inflammatory infiltration and cytokines release. As a pro-inflammatory factor, cyclooxygenase-2 (COX-2) is widely involved in liver inflammation induced by xenobiotics. However, the mechanism by which AFB1-induced COX-2 regulates liver inflammatory injury via hepatocytes-Kupffer cells (KCs) crosstalk remains unclear and requires further elucidation. Here, we established a COX-2 upregulated model with AFB1 treatment in vivo (C57BL/6 mice, 1 mg/kg body weight, i.g, 4 weeks) and in vitro (human liver HepaRG cells, 1 µM for 24 h). In vivo, AFB1-treated mice exhibited NLRP3 inflammasome activation, inflammatory infiltration, and increased recruitment of KCs. In vitro, dephosphorylated COX-2 by protein phosphatase 2A (PP2A)-B55δ promoted NLRP3 inflammasome activation, including mitochondrial translocation of NLRP3, caspase 1 cleavage, and IL-1ß release. Moreover, phosphorylated COX-2 at serine 601 (p-COX-2Ser601) underwent endoplasmic reticulum (ER) retention for proteasome degradation. Furthermore, pyroptosis and inflammatory response induced by AFB1 were relieved with COX-2 genetic (siPTGS2) intervention or pharmaceutic (celecoxib, 30 mg/kg body weight, i.g, 4 weeks) inhibition of COX-2 via NLRP3 inflammasome suppression in vivo and in vitro. Ex vivo, in a co-culture system with murine primary hepatocytes and KCs, activated KCs induced by damaged signals from pyroptotic hepatocytes, formed a feedback loop to amplify NLRP3-dependent pyroptosis of hepatocytes via pro-inflammatory signaling, leading to liver inflammatory injury. Taken together, our data suggest a novel mechanism that protein quality control of COX-2 determines the intracellular distribution and activation of NLRP3 inflammasome, which promotes liver inflammatory injury via hepatocytes-KCs crosstalk.
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Aflatoxina B1/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Ciclo-Oxigenase 2/metabolismo , Hepatócitos/efeitos dos fármacos , Células de Kupffer/efeitos dos fármacos , Piroptose/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Doença Hepática Induzida por Substâncias e Drogas/imunologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Células HEK293 , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Inflamação , Interleucina-1beta/metabolismo , Células de Kupffer/metabolismo , Fígado/efeitos dos fármacos , Fígado/imunologia , Fígado/patologia , Camundongos Endogâmicos C57BL , Fosforilação , Cultura Primária de CélulasRESUMO
Mitophagy, a selective autophagy of mitochondria, clears up damaged mitochondria to maintain cell homeostasis. We performed high-content analysis (HCA) to detect the increase of PINK1, an essential protein controlling mitophagy, in hepatic cells treated with several nanoparticles (NPs). PINK1 immunofluorescence-based HCA was more sensitive than assays and detections for cell viability and mitochondrial functions. Of which, superparamagnetic iron oxide (SPIO)-NPs or graphene oxide-quantum dots (GO-QDs) was selected as representatives for positive or negative inducer of mitophagy. SPIO-NPs, but not GO-QDs, activated PINK1-dependent mitophagy as demonstrated by recruitment of PARKIN to mitochondria and degradation of injured mitochondria. SPIO-NPs caused the loss of mitochondrial membrane potential, decrease in ATP, and increase in mitochondrial reactive oxide species and Ca2+. Blocking mitophagy with PARKIN siRNA aggravated the cytotoxicity of SPIO-NPs. Taken together, PINK1 immunofluorescence-based HCA is considered to be an early, sensitive, and reliable approach to evaluate the bioimpacts of NPs.
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Autofagia , Biomarcadores/análise , Hepatócitos/patologia , Mitocôndrias/patologia , Mitofagia , Nanopartículas/administração & dosagem , Ubiquitina-Proteína Ligases/antagonistas & inibidores , Sobrevivência Celular , Células Cultivadas , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Potencial da Membrana Mitocondrial , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Nanopartículas/química , RNA Interferente Pequeno/genética , Espécies Reativas de Oxigênio/metabolismoRESUMO
The cognitive wireless sensor network (CWSN) is an important development direction of wireless sensor networks (WSNs), and spectrum sensing technology is an essential prerequisite for CWSN to achieve spectrum sharing. However, the existing non-cooperative narrowband spectrum sensing technology has difficulty meeting the application requirements of CWSN at present. In this paper, we present a non-cooperative spectrum sensing algorithm for CWSN, which combines the multi-resolution technique, phase space reconstruction method, and singular spectrum entropy method to sense the spectrum of narrowband wireless signals. Simulation results validate that this algorithm can greatly improve the detection probability at a low signal-to-noise ratio (SNR) (from -19dB to -12dB), and the detector can quickly achieve the best detection performance as the SNR increases. This algorithm could promote the development of CWSN and the application of WSNs.
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Unfolded protein response (UPR) and endoplasmic reticulum (ER)-phagy are essential for cell homeostasis. Quantum dots (QDs), which have been widely used for biomedical applications, can accumulate in the kidney tissues and may cause renal dysfunction. However, the molecular mechanism of QDs-induced nephrotoxicity is still obscure. The present study was aimed to elucidate the role and mechanism of UPR and ER-phagy in QDs-induced nephrotoxicity. Herein, human embyronic kidney (HEK) cells were exposed to 15, 30, 45, and 60 nM cadmium telluride (CdTe)-QDs for 12 and 24 h. And CdTe-QDs (30-60 nM) inhibited the HEK cell viability. The clathrin-dependent endocytosis was determined as the main pathway of CdTe-QDs cellular uptake. Within cells, CdTe-QDs disrupted ER ultrastructure and induced UPR and FAM134B-dependent ER-phagy. Blocking UPR with inhibitors or siRNA rescued the FAM134B-dependent ER-phagy, which was triggered by CdTe-QDs. Moreover, suppression of UPR or FAM134B-dependent ER-phagy restored the cell vability. In vivo, mice were intravenously injected with 8 and 16 nmol/kg body weight CdTe-QDs for 24 h. Kidney was shown as one of highest distributed organs of CdTe-QDs, resulting in renal dysfunction, as well as UPR and FAM134B-dependent ER-phagy in it. Thus, for the first time, we demonstrated that ER-phagy can be triggered by nanomaterials both in vitro and in vivo. In addition, blocking of UPR and ER-phagy showed protective effects against CdTe-QDs-induced toxicity in kideny cells. Notably, a secreted alkaline phosphatase reporter gene system has been developed as a sensitive and rapid method for evaluating the ER quality under the exposure of nanomaterials.
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Compostos de Cádmio/toxicidade , Endocitose , Retículo Endoplasmático/efeitos dos fármacos , Rim/efeitos dos fármacos , Pontos Quânticos/toxicidade , Telúrio/toxicidade , Resposta a Proteínas não Dobradas , Animais , Compostos de Cádmio/administração & dosagem , Linhagem Celular , Retículo Endoplasmático/ultraestrutura , Homeostase , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Proteínas de Neoplasias/metabolismo , Telúrio/administração & dosagemRESUMO
Vibrio cholerae, a natural inhabitant of the marine environment, poses a threat to human health, and its new epidemic variants have been reported. A method of multiplex polymerase chain reaction-capillary electrophoresis-laser-induced fluorescence (PCR-CE-LIF) detection has been developed to detect and identify V. cholerae in marine products sensitively, rapidly, and reliably. Four sets of primers were selected to amplify genus-specific VCC gene, O139 serogroup-specific O139 gene, O1 serogroup-specific O1 gene, and ctxA gene associated with the CT toxin of enterotoxigenic V. cholerae. The PCR products were detected using CE-LIF with SYBR Gold serving as the DNA fluorescent dye. The parameters of PCR and the separation conditions of CE-LIF were optimized. Under the optimal conditions, V. cholerae was detected and four serotypes were identified simultaneously within 8 min. The alignment analysis showed that the PCR products had good agreement with the published sequences from GenBank, indicating that the primers selected in this study had high specificity and the PCR results were reliable. The proposed method could detect 5 to 20 cfu/ml V. cholerae. The intraday precisions of migration time and peak area of DNA marker and PCR products were in the ranges of 1.60-2.56% and 1.60-6.29%, respectively. The specificity results showed that only five standard bacteria used in this study showed the specific peaks when the target bacteria were mixed with seven other common intestinal pathogenic bacteria at the same concentration. The assay was applied to 71 high-risk marine products, and different serotypes of V. cholerae could be identified sensitively and reliably.
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Técnicas Bacteriológicas/métodos , DNA Bacteriano/análise , Eletroforese Capilar , Reação em Cadeia da Polimerase Multiplex , Espectrometria de Fluorescência , Vibrio cholerae/genética , Proteínas de Bactérias/genética , Benzotiazóis , Toxina da Cólera/genética , DNA Bacteriano/química , Diaminas , Corantes Fluorescentes/química , Compostos Orgânicos/química , Quinolinas , Sorogrupo , Sorotipagem/instrumentaçãoRESUMO
This paper proposes a fixed-time tracking control for robot manipulators in the presence of parametric uncertainties and disturbances. An auxiliary function is first proposed for constructing a fixed-time sliding manifold. Benefited from this fixed-time sliding manifold, a singularity-free robust control is proposed to evade the effects of algebraic loop problem of the commonly-used sliding mode controls (SMC). The key advantages of the proposed approach are: (i) exact fixed-time stability featuring the convergence time does not relate to the initial conditions and is acquired in advance; (ii) the singularity and algebraic loop problems are eliminated completely; (iii) a simple and intuitive control structure is used for easy implementation of trajectory tracking control for uncertain robot manipulators with faster transient and higher steady-state precision. Simulations and experimental comparisons validate the improved tracking performance of the proposed approach.
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Chronic graft-versus-host disease (GvHD) is the leading cause of late death in allogenic hematopoietic stem cell transplantation recipients, of which the kidney is a potential target. In this article, we report an extremely rare case of chronic GvHD, characterized by immune complex-mediated diffuse proliferative glomerulonephritis and various autoantibodies detected in the serum; it is the first case of lupus-like chronic GvHD reported to date. The patient responded well to intensive immunosuppressive therapy and reached complete remission. Mycophenolate mofetil was more effective than tacrolimus in this case, suggesting that treatment of kidney diseases associated with chronic GvHD should be based on pathogenesis and pathological patterns.
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Background: Controversy persists regarding the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on cancer. The underlying causal relationship remains unclear. Method: A two-sample Mendelian randomization (MR) strategy was employed to investigate the causal associations between SGLT2 inhibitors and 26 site-specific malignancies. Instrumental variants strongly associated with SLC5A2 gene expression and glycated hemoglobin A1c levels were identified as the genetic proxy for SGLT2 inhibition. Cancer-related outcome datasets sourced from the OpenGWAS project were separated into discovery and replication datasets. The meta-analysis was conducted to determine the final causality. Results: Genetically proxied SGLT2 inhibition showed a significant association with bronchial and lung cancer (beta: -0.028 [-0.041, -0.015], P < 0.001), bladder cancer (beta: 0.018 [0.008, 0.027], P < 0.001), prostate cancer (beta: 1.168 [0.594, 1.742], P < 0.001), cervical cancer (beta: -0.019 [-0.031, -0.008], P = 0.001), corpus uterine cancer (beta: 0.015 [0.006, 0.025], P = 0.001) and non-melanoma skin cancer (beta: -0.080 [-0.116, -0.044], P < 0.001) in the discovery cohort. The suggestive causal effect of SGLT2 inhibition on the increased risk of cervical cancer (beta: 3.241 [0.855, 5.627], P = 0.008) and lymphoid leukemia (beta: 4.126 [0.383, 7.868], P = 0.031) was found in the replication cohort. The combined causality of the following types of cancer was observed to remain significant after meta-analysis: bronchial and lung cancer, bladder cancer, prostate cancer, corpus uterine cancer, and non-melanoma skin cancer (all P ≤ 0.001). Conclusion: For the first time we discovered that the SGLT2 inhibition may exert protection on bronchial and lung cancer and non-melanoma skin cancer from a genetic perspective. However, suggestive higher cancer risks of bladder, prostate, and corpus uteri were also noted, which warrants real-world data validation in the future.
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Introduction: Membranous nephropathy (MN) is the most common cause of proteinuria in syphilis, and neuron-derived neurotrophic factor (NDNF) was recently demonstrated to be the target antigen in syphilis-associated MN. However, the prevalence and clinicopathological characteristics of both NDNF-positive and NDNF-negative MN in Chinese individuals with syphilis infection still remain unknown. Methods: A retrospective study was conducted in 17 patients with MN with history of syphilis infection. The intensity and distribution of NDNF staining, as well as phospholipase A2 receptor (PLA2R) and neural epidermal growth factor-like 1 protein (NELL-1) staining in renal biopsies were assessed. Results: Among the 11 patients with MN with active syphilis infection, positive NDNF staining was shown in 5 patients (46%). The remaining 6 patients demonstrated negative NDNF staining. Of these, 5 patients were PLA2R-positive and 1 patient was PLA2R-negative and NELL-1-negative. Antibiotics were also effective in 3 NDNF-negative patients, suggesting the possibility of syphilis-associated MN. Therefore, the histological positivity rate of NDNF was 63% (5/8 patients) in syphilis-associated MN. In addition, positive NDNF antibody was first confirmed in the serum of 1 patient with NDNF-associated MN. NDNF staining was negative in all 6 patients with MN with previous syphilis infection. Conclusion: Nearly half of the patients with active syphilis infection and MN were NDNF-positive in our study. Positive NDNF staining favors syphilis-associated MN. Circulating anti-NDNF antibody can be detected in the patient's serum sample. In addition, PLA2R or other unknown antigenic protein may also be the target antigens for syphilis-associated MN in Chinese population.
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In recent years, the meat and dairy value of buffaloes has become a major concern in buffalo breeding, and the improvement of buffalo beef quality is key to protecting buffalo germplasm resources and solving the problem of beef supply. MiRNAs play a significant role in regulating muscle development. However, the precise mechanism by which they regulate the development of buffalo skeletal muscles remains largely unexplored. In this study, we examined miRNA expression profiles in buffalo myoblasts during the proliferation and differentiation stages. A total of 177 differentially expressed miRNAs were identified, out of which 88 were up-regulated and 89 down-regulated. We focused on a novel miRNA, named bbu-miR-493-5p, that was significantly differentially expressed during the proliferation and differentiation of buffalo myoblasts and highly expressed in muscle tissues. The RNA-FISH results showed that bbu-miR-493-5p was primarily located in the cytoplasm to encourage buffalo myoblasts' proliferation and differentiation. In conclusion, our study lays the groundwork for future research into the regulatory role of miRNAs in the growth of buffalo muscle.
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Cattle and the draught force provided by its skeletal muscle have been integral to agro-ecosystems of agricultural civilization for millennia. However, relatively little is known about the cattle muscle functional genomics (including protein coding genes, non-coding RNA, etc.). Circular RNAs (circRNAs), as a new class of non-coding RNAs, can be effectively translated into detectable peptides, which enlightened us on the importance of circRNAs in cattle muscle physiology function. Here, RNA-seq, Ribosome profiling (Ribo-seq), and peptidome data are integrated from cattle skeletal muscle, and detected five encoded peptides from circRNAs. It is further identified and functionally characterize a 907-amino acids muscle-specific peptide that is named circNEB-peptide because derived by the splicing of Nebulin (NEB) gene. This peptide localizes to the nucleus and cytoplasm and directly interacts with SKP1 and TPM1, key factors regulating physiological activities of myoblasts, via ubiquitination and myoblast fusion, respectively. The circNEB-peptide is found to promote myoblasts proliferation and differentiation in vitro, and induce muscle regeneration in vivo. These findings suggest circNEB-peptide is an important regulator of skeletal muscle regeneration and underscore the possibility that more encoding polypeptides derived by RNAs currently annotated as non-coding exist.
Assuntos
Multiômica , Proteínas Musculares , RNA Circular , Bovinos , Animais , RNA Circular/genética , RNA Circular/metabolismo , Ecossistema , Músculo Esquelético , Desenvolvimento Muscular/genética , Peptídeos/metabolismoRESUMO
Background and objective: Hypoglycemia is a key barrier to achieving optimal glycemic control in people with diabetes, which has been proven to cause a set of deleterious outcomes, such as impaired cognition, increased cardiovascular disease, and mortality. Hypoglycemia prediction has come to play a role in diabetes management as big data analysis and machine learning (ML) approaches have become increasingly prevalent in recent years. As a result, a review is needed to summarize the existing prediction algorithms and models to guide better clinical practice in hypoglycemia prevention. Materials and methods: PubMed, EMBASE, and the Cochrane Library were searched for relevant studies published between 1 January 2015 and 8 December 2022. Five hypoglycemia prediction aspects were covered: real-time hypoglycemia, mild and severe hypoglycemia, nocturnal hypoglycemia, inpatient hypoglycemia, and other hypoglycemia (postprandial, exercise-related). Results: From the 5,042 records retrieved, we included 79 studies in our analysis. Two major categories of prediction models are identified by an overview of the chosen studies: simple or logistic regression models based on clinical data and data-based ML models (continuous glucose monitoring data is most commonly used). Models utilizing clinical data have identified a variety of risk factors that can lead to hypoglycemic events. Data-driven models based on various techniques such as neural networks, autoregressive, ensemble learning, supervised learning, and mathematical formulas have also revealed suggestive features in cases of hypoglycemia prediction. Conclusion: In this study, we looked deep into the currently established hypoglycemia prediction models and identified hypoglycemia risk factors from various perspectives, which may provide readers with a better understanding of future trends in this topic.