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1.
Phytopathology ; : PHYTO09230326R, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38968142

ABSTRACT

Early detection of rice blast disease is pivotal to ensure rice yield. We collected in situ images of rice blast and constructed a rice blast dataset based on variations in lesion shape, size, and color. Given that rice blast lesions are small and typically exhibit round, oval, and fusiform shapes, we proposed a small object detection model named GCPDFFNet (global context-based parallel differentiation feature fusion network) for rice blast recognition. The GCPDFFNet model has three global context feature extraction modules and two parallel differentiation feature fusion modules. The global context modules are employed to focus on the lesion areas; the parallel differentiation feature fusion modules are used to enhance the recognition effect of small-sized lesions. In addition, we proposed the SCYLLA normalized Wasserstein distance loss function, specifically designed to accelerate model convergence and improve the detection accuracy of rice blast disease. Comparative experiments were conducted on the rice blast dataset to evaluate the performance of the model. The proposed GCPDFFNet model outperformed the baseline network CenterNet, with a significant increase in mean average precision from 83.6 to 95.4% on the rice blast test set while maintaining a satisfactory frames per second drop from 147.9 to 122.1. Our results suggest that the GCPDFFNet model can accurately detect in situ rice blast disease while ensuring the inference speed meets the real-time requirements.

2.
Drug Des Devel Ther ; 18: 2813-2821, 2024.
Article in English | MEDLINE | ID: mdl-38984209

ABSTRACT

Background: Vasopressors remain an important strategy for managing spinal anesthesia-induced hypotension in women with preeclampsia. The aim of this study was to investigate the ED90s and efficacy ratio of phenylephrine and norepinephrine in managing spinal anesthesia-induced hypotension in women with preeclampsia during cesarean delivery. Methods: 60 women with preeclampsia, who underwent cesarean delivery, were randomly assigned to receive either a continuous intravenous infusion of phenylephrine or norepinephrine following spinal anesthesia. The initial dosage of phenylephrine or norepinephrine for the first women was 0.5 or 0.05 µg/kg/min, respectively, and subsequent infusion dosages were adjusted based on their efficacy in preventing spinal anesthesia-induced hypotension (defined as a systolic blood pressure less than 80% of the baseline level). The incremental or decremental doses of phenylephrine or norepinephrine were set at 0.1 or 0.01 µg/kg/min. The primary outcomes were the ED90s and efficacy ratio of phenylephrine and norepinephrine infusions for preventing spinal anesthesia-induced hypotension prior to delivery. Results: The results obtained from isotonic regression analysis revealed that the ED90 values of the phenylephrine and norepinephrine group for preventing spinal anesthesia-induced hypotension were 0.597 (95% CI: 0.582-0.628) and 0.054 (95% CI: 0.053-0.056) µg/kg/min, respectively, with an efficacy ratio of 11.1:1. The results of Probit regression analysis revealed that the ED90 values were determined to be 0.665 (95% CI: 0.576-1.226) and 0.055 (95% CI: 0.047-0.109) µg/kg/min, respectively, with an efficacy ratio of 12.1:1. Conclusion: The administration of 0.6 µg/kg/min phenylephrine and 0.05 µg/kg/min norepinephrine has been found to effectively manage a 90% incidence of spinal anesthesia-induced hypotension in women with preeclampsia.


Subject(s)
Anesthesia, Spinal , Cesarean Section , Hypotension , Norepinephrine , Phenylephrine , Pre-Eclampsia , Humans , Female , Pregnancy , Phenylephrine/administration & dosage , Pre-Eclampsia/drug therapy , Anesthesia, Spinal/adverse effects , Hypotension/prevention & control , Hypotension/chemically induced , Norepinephrine/administration & dosage , Adult , Infusions, Intravenous , Dose-Response Relationship, Drug , Vasoconstrictor Agents/administration & dosage , Blood Pressure/drug effects , Young Adult
3.
Tob Control ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39009449

ABSTRACT

SIGNIFICANCE: Characterisation of tobacco product emissions is an important step in assessing their impact on public health. Accurate and repeatable emissions data require that a leak-tight seal be made between the smoking or vaping machine and the mouth-end of the tobacco product being tested. This requirement is challenging because of the variety of tobacco product mouth-end geometries being puffed on by consumers today. We developed and tested a prototype universal smoking machine adaptor (USMA) that interfaces with existing machines and reliably seals with a variety of tobacco product masses and geometries. METHODS: Emissions were machine-generated using the USMA and other available adaptors for a variety of electronic cigarettes (n=7 brands), cigars (n=4), cigarillos (n=2), a heated tobacco product, and a reference cigarette (1R6F), and mainstream total particulate matter (TPM) and nicotine were quantified. Data variability (precision, n≥10 replicates/brand) for all products and error (accuracy) from certified values (1R6F) were compared across adaptors. RESULTS: TPM and nicotine emissions generated using the USMA were accurate, precise and agreed with certified values for the 1R6F reference cigarette. Replicate data indicate that USMA repeatability across all tobacco products tested generally meets or exceeds that from the comparison adaptors and extant data. CONCLUSION: The USMA seals well with a variety of combustible tobacco products, e-cigarettes with differing geometries and plastic-tipped cigarillos. Variability for all measures was similar or smaller for the USMA compared with other adaptors.

4.
Tob Control ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39009450

ABSTRACT

SIGNIFICANCE: Historically, tobacco product emissions testing using smoking machines has largely focused on combustible products, such as cigarettes and cigars. However, the popularity of newer products, such as electronic cigarettes (e-cigarettes), has complicated emissions testing because the products' mouth-end geometries do not readily seal with existing smoking and vaping machines. The demand for emissions data on popularly used products has led to inefficient and non-standardised solutions, such as laboratories making their geometry-specific custom adaptors and/or employing flexible tubing, for each unique mouth-end geometry tested. A user-friendly, validated, universal smoking machine adaptor (USMA) is needed for testing the variety of tobacco products reflecting consumer use, including e-cigarettes, heated tobacco products, cigarettes, plastic-tipped cigarillos and cigars. METHODS: A prototype USMA that is compatible with existing smoking/vaping machines was designed and fabricated. The quality of the seal between the USMA and different tobacco products, including e-cigarettes, cigars and cigarillos, was evaluated by examining the leak rate. RESULTS: Unlike commercial, product-specific adaptors, the USMA seals well with a wide range of tobacco product mouth-end geometries and masses. This includes e-cigarettes with non-cylindrical mouth ends and cigarillos with cuboid-like plastic tips. USMA leak rates were lower than or equivalent to commercial, product-specific adaptors. CONCLUSION: This report provides initial evidence that the USMA seals reliably with a variety of tobacco product mouth-end geometries and can be used with existing linear smoking/vaping machines to potentially improve the precision, repeatability and reproducibility of machine smoke yield data. Accurate and reproducible emissions testing is critical for regulating tobacco products.

5.
Gut ; 2024 Jul 13.
Article in English | MEDLINE | ID: mdl-38960582

ABSTRACT

OBJECTIVE: Our study aimed to explore the influence of gut microbiota and their metabolites on intracranial aneurysms (IA) progression and pinpoint-related metabolic biomarkers derived from the gut microbiome. DESIGN: We recruited 358 patients with unruptured IA (UIA) and 161 with ruptured IA (RIA) from two distinct geographical regions for conducting an integrated analysis of plasma metabolomics and faecal metagenomics. Machine learning algorithms were employed to develop a classifier model, subsequently validated in an independent cohort. Mouse models of IA were established to verify the potential role of the specific metabolite identified. RESULTS: Distinct shifts in taxonomic and functional profiles of gut microbiota and their related metabolites were observed in different IA stages. Notably, tryptophan metabolites, particularly indoxyl sulfate (IS), were significantly higher in plasma of RIA. Meanwhile, upregulated tryptophanase expression and indole-producing microbiota were observed in gut microbiome of RIA. A model harnessing gut-microbiome-derived tryptophan metabolites demonstrated remarkable efficacy in distinguishing RIA from UIA patients in the validation cohort (AUC=0.97). Gut microbiota depletion by antibiotics decreased plasma IS concentration, reduced IA formation and rupture in mice, and downregulated matrix metalloproteinase-9 expression in aneurysmal walls with elastin degradation reduction. Supplement of IS reversed the effect of gut microbiota depletion. CONCLUSION: Our investigation highlights the potential of gut-microbiome-derived tryptophan metabolites as biomarkers for distinguishing RIA from UIA patients. The findings suggest a novel pathogenic role for gut-microbiome-derived IS in elastin degradation in the IA wall leading to the rupture of IA.

6.
Ren Fail ; 46(2): 2371988, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38952291

ABSTRACT

AIMS: Abnormal renal lipid metabolism causes renal lipid deposition, which leads to the development of renal fibrosis in diabetic kidney disease (DKD). The aim of this study was to investigate the effect and mechanism of chlorogenic acid (CA) on reducing renal lipid accumulation and improving DKD renal fibrosis. METHODS: This study evaluated the effects of CA on renal fibrosis, lipid deposition and lipid metabolism by constructing in vitro and in vivo models of DKD, and detected the improvement of Notch1 and Stat3 signaling pathways. Molecular docking was used to predict the binding between CA and the extracellular domain NRR1 of Notch1 protein. RESULTS: In vitro studies have shown that CA decreased the expression of Fibronectin, α-smooth muscle actin (α-SMA), p-smad3/smad3, alleviated lipid deposition, promoted the expression of carnitine palmitoyl transferase 1 A (CPT1A), and inhibited the expression of cholesterol regulatory element binding protein 1c (SREBP1c). The expression of Notch1, Cleaved Notch1, Hes1, and p-stat3/stat3 were inhibited. These results suggested that CA might reduce intercellular lipid deposition in human kidney cells (HK2) by inhibiting Notch1 and stat3 signaling pathways, thereby improving fibrosis. Further, in vivo studies demonstrated that CA improved renal fibrosis and renal lipid deposition in DKD mice by inhibiting Notch1 and stat3 signaling pathways. Finally, molecular docking experiments showed that the binding energy of CA and NRR1 was -6.6 kcal/mol, which preliminarily predicted the possible action of CA on Notch1 extracellular domain NRR1. CONCLUSION: CA reduces renal lipid accumulation and improves DKD renal fibrosis by inhibiting Notch1 and stat3 signaling pathways.


Subject(s)
Chlorogenic Acid , Diabetic Nephropathies , Fibrosis , Kidney , Lipid Metabolism , Receptor, Notch1 , STAT3 Transcription Factor , Signal Transduction , STAT3 Transcription Factor/metabolism , Receptor, Notch1/metabolism , Diabetic Nephropathies/drug therapy , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/pathology , Animals , Signal Transduction/drug effects , Fibrosis/drug therapy , Chlorogenic Acid/pharmacology , Chlorogenic Acid/therapeutic use , Humans , Mice , Male , Kidney/pathology , Kidney/drug effects , Kidney/metabolism , Lipid Metabolism/drug effects , Molecular Docking Simulation , Mice, Inbred C57BL , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/drug therapy , Cell Line
7.
MedComm (2020) ; 5(8): e627, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39015557

ABSTRACT

Minimal hepatic encephalopathy (MHE) has a substantial impact on the clinical outcomes and quality of life (QOL) of patients with cirrhosis. However, timely diagnosis and intervention are challenging due to sophisticated diagnostic methods. In this study, 673 healthy controls and 905 patients with cirrhosis were screened, and 660 healthy controls and 757 patients with cirrhosis, divided into the test (292 patients) and validation (465 patients) cohort, were analyzed after screening. A diagnostic model of the Stroop test (Stroop-CN) was constructed by multivariate linear regression based on the results of healthy controls. The prevalence of MHE and the comparison results with psychometric hepatic encephalopathy score through the Stroop-CN model were stable in the test and validation cohorts. Moreover, the prevalence of MHE remained significantly higher in patients with worse disease conditions marked as high Child-Pugh grades and the Model for End-stage Liver Disease and Sodium (MELD-Na) scores in the test and validation cohort. The EuroQol 5-D questionnaire revealed that patients with MHE had a worse QOL than those without MHE both in the test and validation cohort. In conclusion, an easy and practical Stroop-CN model for MHE diagnosis based on the EncephalApp is established. It is found that a considerable number of Chinese patients with cirrhosis experience MHE, which significantly impacts their QOL.

8.
Eur J Med Res ; 29(1): 366, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39014466

ABSTRACT

PURPOSE: Our study aimed to develop and validate a homologous recombination deficiency (HRD) scoring algorithm in the Chinese breast cancer population. METHODS AND MATERIALS: Ninety-six in-house breast cancer (BC) samples and 6 HRD-positive standard cells were analyzed by whole-genome sequencing (WGS). Besides, 122 BCs from the TCGA database were down-sampled to ~ 1X WGS. We constructed an algorithm named AcornHRD for HRD score calculated based on WGS at low coverage as input data to estimate large-scale copy number alteration (LCNA) events on the genome. A clinical cohort of 50 BCs (15 cases carrying BRCA mutation) was used to assess the association between HRD status and anthracyclines-based neoadjuvant treatment outcomes. RESULTS: A 100-kb window was defined as the optimal size using 41 in-house cases and the TCGA dataset. HRD score high threshold was determined as HRD score ≥ 10 using 55 in-house BCs with BRCA mutation to achieve a 95% BRCA-positive agreement rate. Furthermore, the HRD status agreement rate of AcornHRD is 100%, while the ShallowHRD is 60% in standard cells. BRCA mutation was significantly associated with a high HRD score evaluated by AcornHRD and ShallowHRD (p = 0.008 and p = 0.003, respectively) in the TCGA dataset. However, AcornHRD showed a higher positive agreement rate than did the ShallowHRD algorithm (70% vs 60%). In addition, the BRCA-positive agreement rate of AcornHRD was superior to that of ShallowHRD (87% vs 13%) in the clinical cohort. Importantly, the high HRD score assessed by AcornHRD was significantly correlated with a residual cancer burden score of 0 or 1 (RCB0/1). Besides, the HRD-positive group was more likely to respond to anthracycline-based chemotherapy than the HRD-negative group (pCR [OR = 9.5, 95% CI 1.11-81.5, p = 0.040] and RCB0/1 [OR = 10.29, 95% CI 2.02-52.36, p = 0.005]). CONCLUSION: Using the AcornHRD algorithm evaluation, our analysis demonstrated the high performance of the LCNA genomic signature for HRD detection in breast cancers.


Subject(s)
Algorithms , Anthracyclines , Breast Neoplasms , Neoadjuvant Therapy , Humans , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Female , Anthracyclines/therapeutic use , Anthracyclines/administration & dosage , Neoadjuvant Therapy/methods , Middle Aged , China/epidemiology , Adult , Homologous Recombination , Mutation , Aged , DNA Copy Number Variations , BRCA1 Protein/genetics
9.
Epilepsy Behav ; 157: 109868, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38823075

ABSTRACT

BACKGROUND: Previous research has demonstrated that neuroinflammation is a key element in the progress of epilepsy. Nevertheless, it is currently unidentified which inflammatory factors and proteins increase or decrease the risk of epilepsy. METHODS: We adopted Mendelian randomization techniques to explore the causal relationship between circulating inflammatory factors and proteins and various epilepsy. Our principal approach was inverse variance weighting, supplemented by several sensitivity analyses to guarantee the robustness of our findings. RESULTS: Studies have identified associations between epilepsy and specific inflammatory factors and proteins: three inflammatory factors and six proteins are linked to epilepsy in general; one inflammatory factor and four proteins are associated with focal epilepsy with no documented lesions; two inflammatory factors and three proteins are related to focal epilepsy, excluding cases with hippocampal sclerosis; two inflammatory factors and two proteins are connected to juvenile myoclonic epilepsy; two inflammatory factors and five proteins are linked to juvenile absence epilepsy; four inflammatory proteins are associated with childhood absence epilepsy; two inflammatory factors are related to focal epilepsy overall; two inflammatory factors and two proteins are connected to generalized epilepsy; and two inflammatory proteins are linked to generalized epilepsy with tonic-clonic seizures. Additionally, six inflammatory factors may play a downstream role in focal epilepsy. CONCLUSION: Our study uncovers various inflammatory factors and proteins that influence the risk of epilepsy, offering instructive insights to the diagnosis and therapy of the condition.

10.
Oral Dis ; 2024 Jun 09.
Article in English | MEDLINE | ID: mdl-38852162

ABSTRACT

OBJECTIVE: This study focused on the metabolic characteristics of tongue coating in patients with intra-oral halitosis (IOH) to investigate potential diagnostic biomarkers for IOH. METHODS: Oral healthy participants were enrolled in this study. Halitosis was evaluated with an organoleptic assessment, a Halimeter®, and an OralChroma™. Tongue coating samples were collected from 18 halitosis patients and 18 healthy controls. Liquid chromatography-mass spectrometry was conducted to reveal the IOH-related metabolic variations in tongue coating. RESULTS: A total of 2214 metabolites were obtained. Most metabolites were shared between the two groups. A total of 274 upregulated metabolites, such as paramethasone acetate and indole-3-acetic acid, and 43 downregulated metabolites, including deoxyadenosine and valyl-arginine, were detected in the halitosis group. Functional analysis indicated that several metabolic pathways, including arginine biosynthesis, arginine and proline metabolism, histidine metabolism, and lysine degradation were significantly enriched in the IOH group. The least absolute shrinkage and selection operator logistic regression analysis revealed that paramethasone acetate, {1-[2-(4-carbamimidoyl-benzoylamino)-propionyl]-piperidin-4-yloxy}-acetic acid, indole-3-acetic acid, and valyl-arginine were remarkably associated with IOH. CONCLUSIONS: This study revealed the metabolites present in tongue coating and identified effective biomarkers, providing essential insights into the prediction, pathogenesis, and diagnosis of IOH.

11.
Ecol Evol ; 14(6): e11575, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38932953

ABSTRACT

With 75 known species, the freshwater fish genus Sinocyclocheilus is the largest cavefish radiation in the world and shows multiple adaptations for cave-dwelling (stygomorphic adaptations), which include a range of traits such as eye degeneration (normal-eyed, micro-eyed and eyeless), depigmentation of skin, and in some species, the presence of "horns". Their behavioural adaptations to subterranean environments, however, are poorly understood. Wall-following (WF) behaviour, where an organism remains in close contact with the boundary demarcating its habitat when in the dark, is a peculiar behaviour observed in a wide range of animals and is enhanced in cave dwellers. Hence, we hypothesise that wall-following is also present in Sinocyclocheilus, possibly enhanced in eyeless species compared to eye bearing (normal-/micro-eyed species). Using 13 species representative of Sinocyclocheilus radiation and eye morphs, we designed a series of assays, based on pre-existing methods for Astyanax mexicanus behavioural experiments, to examine wall-following behaviour under three conditions. Our results indicate that eyeless species exhibit significantly enhanced intensities of WF compared to normal-eyed species, with micro-eyed forms demonstrating intermediate intensities in the WF distance. Using a mtDNA based dated phylogeny (chronogram with four clades A-D), we traced the degree of WF of these forms to outline common patterns. We show that the intensity of WF behaviour is higher in the subterranean clades compared to clades dominated by normal-eyed free-living species. We also found that eyeless species are highly sensitive to vibrations, whereas normal-eyed species are the least sensitive. Since WF behaviour is presented to some degree in all Sinocyclocheilus species, and given that these fishes evolved in the late Miocene, we identify this behaviour as being ancestral with WF enhancement related to cave occupation. Results from this diversification-scale study of cavefish behaviour suggest that enhanced wall-following behaviour may be a convergent trait across all stygomorphic lineages.

12.
Heliyon ; 10(11): e31781, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38828331

ABSTRACT

The aim of the study is to create and validate a model of the relationship between specialization in leisure activities, the individual's adaptation to the environment and the heart flow experience. In order to clarify the role of the individual's adaptation to the environment in the relationship between specialization in leisure activities and the heart flow experience. The study utilized purposive sampling, cluster sampling, and random sampling. Using questionnaires and interviews to survey 525 cycling enthusiasts. Descriptive analysis, model construction and testing of the constructed path relationships were conducted using SPSS 20.0 and Amos 20.0. The results indicate that the model of the relationship between recovery specialization, individual-environment fit and heart flow experience has a good overall fit. The model shows good reliability and validity. Cyclists' recreational specialization has a statistically significant effect on individual-environment fit (ß = 0.38, P < 0.001). The fit between individual and environment has a statistically significant influence on the heart flow experience (ß = 0.39, P < 0.001). The fit between individual and environment serves as a mediating variable between recreational specialization and the heart flow experience, with the path showing statistical significance (ß = 0.15, P < 0.001). Recreational specialization has a statistically significant effect on the heart flow experience (ß = 0.30, P < 0.001). And the overall path of the effects of recreational specialization of cyclists on the fit between individual and environment is (ß = 0.45, P < 0.001), with the path showing statistical significance. Conclusion: The stronger the recreational specialization of cyclists and the greater the fit between individual and environment, the stronger their heart flow experience. The fit between individual and environment plays a partially mediating role.

13.
Opt Express ; 32(8): 13562-13573, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38859323

ABSTRACT

We propose a method for simulating a 1D non-Hermitian Su-Schrieffer-Heeger model with modulated nonreciprocal hopping using a cyclic three-mode optical system. The current system exhibits different localization of topologically nontrivial phases, which can be characterized by the winding number. We find that the eigenenergies of such a system undergo a real-complex transition as the nonreciprocal hopping changes, accompanied by a non-Bloch parity-time symmetry breaking. We explain this phase transition by considering the evolution of saddle points on the complex energy plan and the ratio of complex eigenenergies. Additionally, we demonstrate that the skin states resulting from the non-Hermitian skin effect possess higher-order exceptional points under the critical point of the non-Bloch parity-time phase transition. Furthermore, we investigate the non-Hermitian skin phase transition by the directional mean inverse participation ratio and the generalized Brillouin zone. This work provides an alternative way to investigate the novel topological and non-Hermitian effects in nonreciprocal optical systems.

15.
J Cardiovasc Pharmacol ; 84(1): 45-57, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38922585

ABSTRACT

ABSTRACT: Atherosclerosis (AS) is a chronic progressive disease caused by various factors and causes various cerebrovascular and cardiovascular diseases (CVDs). Reducing the plasma levels of low-density lipoprotein cholesterol is the primary goal in preventing and treating AS. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a crucial role in regulating low-density lipoprotein cholesterol metabolism. Panax notoginseng has potent lipid-reducing effects and protects against CVDs, and its saponins induce vascular dilatation, inhibit thrombus formation, and are used in treating CVDs. However, the anti-AS effect of the secondary metabolite, 20( S )-protopanaxatriol (20( S )-PPT), remains unclear. In this study, the anti-AS effect and molecular mechanism of 20( S )-PPT were investigated in vivo and in vitro by Western blotting, real-time polymerase chain reaction, enzyme-linked immunosorbent assay, immunofluorescence staining, and other assays. The in vitro experiments revealed that 20( S )-PPT reduced the levels of PCSK9 in the supernatant of HepG2 cells, upregulated low-density lipoprotein receptor protein levels, promoted low-density lipoprotein uptake by HepG2 cells, and reduced PCSK9 mRNA transcription by upregulating the levels of forkhead box O3 protein and mRNA and decreasing the levels of HNF1α and SREBP2 protein and mRNA. The in vivo experiments revealed that 20( S )-PPT upregulated aortic α-smooth muscle actin expression, increased the stability of atherosclerotic plaques, and reduced aortic plaque formation induced by a high-cholesterol diet in ApoE -/- mice (high-cholesterol diet-fed group). Additionally, 20( S )-PPT reduced the aortic expression of CD68, reduced inflammation in the aortic root, and alleviated the hepatic lesions in the high-cholesterol diet-fed group. The study revealed that 20( S )-PPT inhibited low-density lipoprotein receptor degradation via PCSK9 to alleviate AS.


Subject(s)
Aorta , Aortic Diseases , Atherosclerosis , Disease Models, Animal , Mice, Inbred C57BL , Mice, Knockout, ApoE , Plaque, Atherosclerotic , Proprotein Convertase 9 , Receptors, LDL , Sapogenins , Animals , Atherosclerosis/metabolism , Atherosclerosis/pathology , Atherosclerosis/drug therapy , Atherosclerosis/prevention & control , Atherosclerosis/genetics , Sapogenins/pharmacology , Proprotein Convertase 9/metabolism , Proprotein Convertase 9/genetics , Receptors, LDL/genetics , Receptors, LDL/metabolism , Humans , Male , Aortic Diseases/pathology , Aortic Diseases/prevention & control , Aortic Diseases/metabolism , Aortic Diseases/genetics , Aortic Diseases/drug therapy , Aorta/drug effects , Aorta/metabolism , Aorta/pathology , Proteolysis/drug effects , Hep G2 Cells , PCSK9 Inhibitors , Signal Transduction/drug effects , Sterol Regulatory Element Binding Protein 2/metabolism , Sterol Regulatory Element Binding Protein 2/genetics , Mice , Diet, High-Fat , Apolipoproteins E
16.
Antiviral Res ; 228: 105936, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38908520

ABSTRACT

Herpes simplex virus-1 (HSV-1) infection can cause various diseases and the current therapeutics have limited efficacy. Small interfering RNA (siRNA) therapeutics are a promising approach against infectious diseases by targeting the viral mRNAs directly. Recently, we employed a novel tRNA scaffold to produce recombinant siRNA agents with few natural posttranscriptional modifications. In this study, we aimed to develop a specific prodrug against HSV-1 infection based on siRNA therapeutics by bioengineering technology. We screened and found that UL8 of the HSV-1 genome was an ideal antiviral target based on RNAi. Next, we used a novel bio-engineering approach to manufacture recombinant UL8-siRNA (r/si-UL8) in Escherichia coli with high purity and activity. The r/si-UL8 was selectively processed to mature si-UL8 and significantly reduced the number of infectious virions in human cells. r/si-UL8 delivered by flexible nano-liposomes significantly decreased the viral load in the skin and improved the survival rate in the preventive mouse zosteriform model. Furthermore, r/si-UL8 also effectively inhibited HSV-1 infection in a 3D human epidermal skin model. Taken together, our results highlight that the novel siRNA bioengineering technology is a unique addition to the conventional approach for siRNA therapeutics and r/si-UL8 may be a promising prodrug for curing HSV-1 infection.


Subject(s)
Bioengineering , Herpes Simplex , Herpesvirus 1, Human , Liposomes , RNA, Small Interfering , Herpesvirus 1, Human/drug effects , Herpesvirus 1, Human/genetics , RNA, Small Interfering/administration & dosage , RNA, Small Interfering/genetics , Animals , Mice , Herpes Simplex/drug therapy , Herpes Simplex/prevention & control , Humans , Bioengineering/methods , Antiviral Agents/pharmacology , Antiviral Agents/administration & dosage , Viral Proteins/genetics , Viral Load/drug effects , Mice, Inbred BALB C , Nanoparticles/chemistry , Female , RNA Interference
17.
Nanomaterials (Basel) ; 14(12)2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38921896

ABSTRACT

Doping inorganic acid ions represents a promising pathway to improving the photocatalytic activity of TiO2, and oxygen vacancy has been regarded as the determinant factor for photocatalytic activity. A series of samples doped with Cl-, NO3-, and SO42- was prepared via a simple sol-gel method. Two different oxygen vacancies in the crystal layer of NO3-/TiO2 and Cl-/TiO2 were found, and those are [Ti3+]-V0-[Ti3+] and [Ti3+]-Cl, respectively. The photocurrent of NO3-/TiO2 with [Ti3+]-V0-[Ti3+] is significantly greater than that of Cl-/TiO2 with [Ti3+]-Cl. The least oxygen vacancy is in the gel layer of SO42-/TiO2, and the negligible photocurrent is due to difficulty in forming a stable sol. Furthermore, the process conditions for the application of TiO2 were investigated in this work. The optimal process parameters are to adjust the solution to pH = 3 during sol-gel preparation, to adopt 550 °C as the calcination temperature, and to use an alkaline electrolyte, while the rest of the preparation conditions remain unchanged. This work reveals a new avenue for designing efficient photocatalysts for air pollutant degradation.

18.
Transl Cancer Res ; 13(4): 1924-1935, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38737695

ABSTRACT

Background: Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) contribute to more than 95% of thyroid malignancies. However, synchronous PTC and FTC are less common; it is most commonly discovered incidentally as synchronous malignancies during operation, which adds difficulties to intraoperative decision-making and postoperative treatment. Therefore, we analyzed the clinicopathological characteristics and prognosis of patients with PTC and FTC in our center. Methods: We conducted a search of single PTC, single FTC, and synchronous PTC/FTC patients who received initial surgery treatment at Fudan University Shanghai Cancer Center from 2006 to 2018 and collected paraffin-embedded samples of synchronous patients. Clinicopathological characteristics were collected from the electronic medical record system. Follow-up was performed through telephone contact or medical records. Exome sequencing was performed by ThyroLead panel. Results: Total of 42 synchronous PTC/FTC patients, 244 single FTC patients, and 2,959 single PTC patients were included. It showed a similarity between the clinicopathological features of synchronous thyroid cancer patients and single PTC patients, with a greater proportion of females, higher probabilities of lymph node metastasis, and higher rate of concurrence of Hashimoto's disease. The disease-free survival (DFS) curve indicated a worse prognosis of the synchronous group and single PTC group compared to the single FTC group, who had a propensity for neck lymph node recurrence; however, logistic multivariate regression analysis did not find any factor related to recurrence in the synchronous group. After re-checking pathology, DNA extraction, and quality control, genetic alteration information of 62 samples including primary tumors and metastatic lymph nodes from 35 synchronous cancer patients was displayed. In total, 81 mutations and 1 fusion gene were identified, including mutations related to outcomes and targeted therapy. Besides, some rare mutations in thyroid cancer were found in these patients. Conclusions: To conclude, synchronous PTC/FTC tend to be incidentally discovered during or after operation, behaving more like single PTC. The prognosis of synchronous patients is worse than that of single FTC patients and supplemental cervical lymph node dissection, total thyroidectomy, and postoperative radioiodine therapy should be taken into consideration after diagnosis. The next-generation sequencing (NGS) showed a unique molecular feature of synchronous patients with some rare mutations.

19.
Small ; : e2400036, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38747043

ABSTRACT

Electrocatalytic conversion of nitrates and carbon dioxide to urea under ambient conditions shows promise as a potential substitute for traditional urea synthesis processes characterized by high consumption and pollution. In this study, a straightforward one-pot method is employed to prepare a highly efficient FeNC-Fe1N4 electrocatalyst, consisting of atomically dispersed Fe1N4 sites and metallic Fe clusters (FeNC) with particle size of 4-7 nm. The FeNC-Fe1N4 catalyst exhibits remarkable electrocatalytic activity for urea synthesis from nitrate anion (NO3 -) and carbon dioxide (CO2), achieving a urea production rate of 38.2 mmol gcat -1 h-1 at -0.9 V (vs RHE) and a Faradaic efficiency of 66.5% at -0.6 V (vs RHE). Both experimental and theoretical results conclusively demonstrate that metallic Fe clusters and Fe1N4 species provide active sites for the adsorption and activation of NO3 - and CO2, respectively, and the synergistic effect between Fe1N4 and metallic Fe clusters significantly enhances the electrochemical efficiency of urea synthesis. In all, this work contributes to the rational design and comprehensive synthesis of a dual-active site iron-based electrocatalyst, facilitating efficient and sustainable urea synthesis.

20.
Front Microbiol ; 15: 1384991, 2024.
Article in English | MEDLINE | ID: mdl-38800755

ABSTRACT

Introduction: Rapid identification of infected individuals through viral RNA or antigen detection followed by effective personal isolation is usually the most effective way to prevent the spread of a newly emerging virus. Large-scale detection involves mass specimen collection and transportation. For biosafety reasons, denaturing viral transport medium has been extensively used during the SARS-CoV-2 pandemic. However, the high concentrations of guanidinium isothiocyanate (GITC) in such media have raised issues around sufficient GITC supply and laboratory safety. Moreover, there is a lack of denaturing transport media compatible with SARS-CoV-2 RNA and antigen detection. Methods: Here, we tested whether supplementing media containing low concentrations of GITC with ammonium sulfate (AS) would affect the throat-swab detection of SARS-CoV-2 or a viral inactivation assay targeting coronavirus and other enveloped and non-enveloped viruses. The effect of adding AS to the media on RNA stability and its compatibility with SARS-CoV-2 antigen detection were also tested. Results and discussion: We found that adding AS to the denaturing transport media reduced the need for high levels of GITC, improved SARS-COV-2 RNA detection without compromising virus inactivation, and enabled the denaturing transport media compatible with SARS-CoV-2 antigen detection.

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