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1.
Front Pharmacol ; 15: 1392338, 2024.
Article in English | MEDLINE | ID: mdl-38966547

ABSTRACT

Introduction: Alcohol consumption alters the diversity and metabolic activities of gut microbiota, leading to intestinal barrier dysfunction and contributing to the development of alcoholic liver disease (ALD), which is the most prevalent cause of advanced liver diseases. In this study, we investigated the protective effects and action mechanism of an aqueous extraction of Pericarpium citri reticulatae and Amomi fructus (PFE) on alcoholic liver injury. Methods: C57BL/6 mice were used to establish the mouse model of alcoholic liver injury and orally administered 500 and 1,000 mg/kg/d of PFE for 2 weeks. Histopathology, immunohistochemistry, immunofluorescence, Western blotting, qRT-PCR, and 16S rDNA amplicon sequencing were used to analyze the mechanism of action of PFE in the treatment of alcohol-induced liver injury. Results: Treatment with PFE significantly improved alcohol-induced liver injury, as illustrated by the normalization of serum alanine aminotransferase, aspartate aminotransferase, total triglyceride, and cholesterol levels in ALD mice in a dose-dependent manner. Administration of PFE not only maintained the intestinal barrier integrity prominently by upregulating mucous production and tight junction protein expressions but also sensibly reversed the dysregulation of intestinal microecology in alcohol-treated mice. Furthermore, PFE treatment significantly reduced hepatic lipopolysaccharide (LPS) and attenuated oxidative stress as well as inflammation related to the TLR4/NF-κB signaling pathway. The PFE supplementation also significantly promoted the production of short-chain fatty acids (SCFAs) in the ALD mice. Conclusion: Administration of PFE effectively prevents alcohol-induced liver injury and may also regulate the LPS-involved gut-liver axis; this could provide valuable insights for the development of drugs to prevent and treat ALD.

2.
Front Pharmacol ; 15: 1396641, 2024.
Article in English | MEDLINE | ID: mdl-38725660

ABSTRACT

Type 2 diabetes mellitus is regarded as a chronic metabolic disease characterized by hyperglycemia. Long-term hyperglycemia may result in oxidative stress, damage pancreatic ß-cell function and induce insulin resistance. Herein we explored the anti-hypoglycemic effects and mechanisms of action of N-p-coumaroyloctopamine (N-p-CO) in vitro and in vivo. N-p-CO exhibited high antioxidant activity, as indicated by the increased activity of SOD, GSH and GSH-Px in HL-7702 cells induced by both high glucose (HG) and palmitic acid (PA). N-p-CO treatment significantly augmented glucose uptake and glycogen synthesis in HG/PA-treated HL-7702 cells. Moreover, administration of N-p-CO in diabetic mice induced by both high-fat diet (HFD) and streptozotocin (STZ) not only significantly increased the antioxidant levels of GSH-PX, SOD and GSH, but also dramatically alleviated hyperglycemia and hepatic glucose metabolism in a dose-dependent manner. More importantly, N-p-CO upregulated the expressions of PI3K, AKT and GSK3ß proteins in both HG/PA-induced HL-7702 cells and HFD/STZ-induced mice. These findings clearly suggest that N-p-CO exerts anti-hypoglycemic and anti-oxidant effects, most probably via the regulation of a PI3K/AKT/GSK3ß signaling pathway. Thus, N-p-CO may have high potentials as a new candidate for the prevention and treatment of diabetes.

3.
J Nat Med ; 2024 May 22.
Article in English | MEDLINE | ID: mdl-38775895

ABSTRACT

The practice of Chinese herbal medicines for the treatment of COVID-19 in China played an essential role for the control of mortality rate and reduction of recovery time. The iridoids is one of the main constituents of many heat-clearing and detoxifying Chinese medicines that were largely planted and frequently used in clinical practice. Twenty-three representative high content iridoids from several staple Chinese medicines were obtained and tested by a SARS-CoV-2 pseudo-virus entry-inhibition assay on HEK-293 T/ACE2 cells, a live HCoV-OC43 virus infection assay on HRT-18 cells, and a SARS-CoV-2 3CL protease inhibitory FRET assay followed by molecular docking simulation. The anti-pulmonary inflammation activities were further evaluated on a TNF-α induced inflammation model in A549 cells and preliminary SARs were concluded. The results showed that specnuezhenide (7), cornuside (12), neonuezhenide (15), and picroside III (21) exhibited promising antiviral activities, and neonuezhenide (15) could inhibit 3CL protease with an IC50 of 14.3 µM. Docking computation showed that compound 15 could bind to 3CL protease through a variety of hydrogen bonding and hydrophobic interactions. In the anti-pulmonary inflammation test, cornuside (12), aucubin (16), monotropein (17), and shanzhiside methyl ester (18) could strongly decrease the content of IL-1ß and IL-8 at 10 µM. Compound 17 could also upregulate the expression of the anti-inflammatory cytokine IL-10 significantly. The iridoids exhibited both anti-coronavirus and anti-pulmonary inflammation activities for their significance of existence in Chinese herbal medicines, which also provided a theoretical basis for their potential utilization in the pharmaceutical and food industries.

4.
Insects ; 15(5)2024 May 11.
Article in English | MEDLINE | ID: mdl-38786901

ABSTRACT

The overuse of synthetic insecticides has led to various negative consequences, including insecticide resistance, environmental pollution, and harm to public health. This may be ameliorated by using insecticides derived from botanical sources. The primary objective of this study was to evaluate the anti-mosquito activity of the essential oil (EO) of Citrus reticulata Blanco cv. Chachiensis (Chachi) (referred to as CRB) at immature, semi-mature, and mature stages. The chemical compositions of the CRB EO were analyzed using GC-MS. The main components were identified to be D-limonene and γ-terpinene. The contents of D-limonene at the immature, semi-mature, and mature stages were 62.35%, 76.72%, and 73.15%, respectively; the corresponding contents of γ-terpinene were 14.26%, 11.04%, and 11.27%, respectively. In addition, the corresponding contents of a characteristic component, methyl 2-aminobenzoate, were 4.95%, 1.93%, and 2.15%, respectively. CRB EO exhibited significant larvicidal activity against Aedes albopictus (Ae. albopictus, Diptera: Culicidae), with the 50% lethal doses being 65.32, 61.47, and 65.91 mg/L for immature, semi-mature, and mature CRB EO, respectively. CRB EO was able to inhibit acetylcholinesterase and three detoxification enzymes, significantly reduce the diversity of internal microbiota in mosquitoes, and decrease the relative abundance of core species within the microbiota. The present results may provide novel insights into the utilization of plant-derived essential oils in anti-mosquitoes.

5.
Int J Mol Sci ; 25(10)2024 May 17.
Article in English | MEDLINE | ID: mdl-38791522

ABSTRACT

The role of lncRNA and circRNA in wheat grain development is still unclear. The objectives of this study were to characterize the lncRNA and circRNA in the wheat grain development and to construct the interaction network among lncRNA, circRNA, and their target miRNA to propose a lncRNA-circRNA-miRNA module related to wheat grain development. Full transcriptome sequencing on two wheat varieties (Annong 0942 and Anke 2005) with significant differences in 1000-grain weight at 10 d (days after pollination), 20 d, and 30 d of grain development were conducted. We detected 650, 736, and 609 differentially expressed lncRNA genes, and 769, 1054, and 1062 differentially expressed circRNA genes in the grains of 10 days, 20 days and 30 days after pollination between Annong 0942 and Anke 2005, respectively. An analysis of the lncRNA-miRNA and circRNA-miRNA targeting networks reveals that circRNAs exhibit a more complex and extensive interaction network in the development of cereal grains and the formation of grain shape. Central to these interactions are tae-miR1177, tae-miR1128, and tae-miR1130b-3p. In contrast, lncRNA genes only form a singular network centered around tae-miR1133 and tae-miR5175-5p when comparing between varieties. Further analysis is conducted on the underlying genes of all target miRNAs, we identified TaNF-YB1 targeted by tae-miR1122a and TaTGW-7B targeted by miR1130a as two pivotal regulatory genes in the development of wheat grains. The quantitative real-time PCR (qRT-PCR) and dual-luciferase reporter assays confirmed the target regulatory relationships between miR1130a-TaTGW-7B and miR1122a-TaNF-YB1. We propose a network of circRNA and miRNA-mediated gene regulation in the development of wheat grains.


Subject(s)
Edible Grain , Gene Expression Regulation, Plant , MicroRNAs , RNA, Circular , RNA, Long Noncoding , Triticum , Triticum/genetics , Triticum/growth & development , RNA, Long Noncoding/genetics , RNA, Circular/genetics , RNA, Circular/metabolism , MicroRNAs/genetics , Edible Grain/genetics , Edible Grain/growth & development , Gene Regulatory Networks , RNA, Plant/genetics , Gene Expression Profiling
6.
Prev Med Rep ; 41: 102722, 2024 May.
Article in English | MEDLINE | ID: mdl-38646072

ABSTRACT

Background: To describe the past, present and future burden of pancreatitis in older adults, and to explore cross-national inequalities across socio-demographic index (SDI). Methods: Data on pancreatitis in older adults, including mortality and disability-adjusted life years (DALYs) rates, were collected from the Global Burden of Disease (GBD) 2019 study. Temporal trends were measured using joinpoint analyses and predicted using a Bayesian age-period-cohort model. Additionally, the unequal distribution of the burden of pancreatitis in older adults was quantified. Results: From 1990 to 2019, the number of deaths and DALYs due to pancreatitis in older adults has been increasing annually. However, in most regions of the world, age-standardized death rates (ASDR) and age-standardized DALYs rates have been declining. The burden of pancreatitis in older adults was highest in low SDI region, primarily affecting the population aged 65-74, with a greater burden on males than females. Furthermore, from 1990 to 2019, absolute and relative cross-national inequalities in pancreatitis among older adults have remained largely unchanged. It is projected that in the next 11 years, the number of deaths in older adults due to pancreatitis will continue to increase, but the ASDR is expected to decline. Conclusion: Over the past 30 years, the ASDR and age-standardized DALYs rate of pancreatitis in older adults have shown a decline globally, but the absolute burden continues to increase. Cross-national health inequalities persist. Therefore, it is necessary to develop targeted intervention measures and enhance awareness among this vulnerable population regarding the risk factors associated with pancreatitis.

7.
Antioxidants (Basel) ; 13(4)2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38671925

ABSTRACT

Cannabis and its major cannabinoid cannabidiol (CBD) are reported to exhibit anticancer activity against skin tumors. However, the cytotoxic effects of other minor cannabinoids and synthetic CBD derivatives in melanoma are not fully elucidated. Herein, the antiproliferative activity of a panel of phytocannabinoids was screened against murine (B16F10) and human (A375) melanoma cells. CBD was the most cytotoxic natural cannabinoid with respective IC50 of 28.6 and 51.6 µM. Further assessment of the cytotoxicity of synthetic CBD derivatives in B16F10 cells identified two bipiperidinyl group-bearing derivatives (22 and 34) with enhanced cytotoxicity (IC50 = 3.1 and 8.5 µM, respectively). Furthermore, several cell death assays including flow cytometric (for apoptosis and ferroptosis) and lactate dehydrogenase (for pyroptosis) assays were used to characterize the antiproliferative activity of CBD and its bipiperidinyl derivatives. The augmented cytotoxicity of 22 and 34 in B16F10 cells was attributed to their capacity to promote apoptosis (as evidenced by increased apoptotic population). Taken together, this study supports the notion that CBD and its derivatives are promising lead compounds for cannabinoid-based interventions for melanoma management.

8.
ACS Appl Mater Interfaces ; 16(13): 16601-16611, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38502203

ABSTRACT

Carbon Quantum dots (CQDs) are widely studied because of their good optical and electronic characteristics and because they can easily generate photocarriers. Nitrogen-doped CQDs (NCQDs) may exhibit improved hydrophilic, optical, and electron-transfer properties, which are conducive to photocatalytic hydrogen evolution. In this paper, NCQD-modified ZnS catalysts were successfully prepared. Under the irradiation of the full spectrum, the H2 evolution rate of the optimal catalyst 0.25 wt % NCQDs/ZnS achieves 5.70 mmol g-1 h-1, which is 11.88, 43.84, and 5.14 times the values of ZnS (0.48 mmol g-1 h-1), NCQDs (0.13 mmol g-1 h-1), and CQDs/ZnS (1.11 mmol g-1 h-1), respectively. Furthermore, it shows good stability, indicating that the modification of NCQDs prevents the photocorrosion and oxidation of ZnS. The enhanced performance is due to NCQD loading, which promotes the separation of photogenerated carriers, optimizes the structures, and increases the specific surface area. This work highlights the fact that NCQD-modified ZnS may afford a new strategy to synthesize ZnS-based photocatalysts with enhanced H2 production performance.

9.
Front Microbiol ; 15: 1323887, 2024.
Article in English | MEDLINE | ID: mdl-38410396

ABSTRACT

Introduction: The pivotal roles of both abundant and rare bacteria in ecosystem function are widely acknowledged. Despite this, the diversity elevational patterns of these two bacterial taxa in different seasons and influencing factors remains underexplored, especially in the case of rare bacteria. Methods: Here, a metabarcoding approach was employed to investigate elevational patterns of these two bacterial communities in different seasons and tested the roles of soil physico-chemical properties in structuring these abundant and rare bacterial community. Results and discussion: Our findings revealed that variation in elevation and season exerted notably effects on the rare bacterial diversity. Despite the reactions of abundant and rare communities to the elevational gradient exhibited similarities during both summer and winter, distinct elevational patterns were observed in their respective diversity. Specifically, abundant bacterial diversity exhibited a roughly U-shaped pattern along the elevation gradient, while rare bacterial diversity increased with the elevational gradient. Soil moisture and N:P were the dominant factor leading to the pronounced divergence in elevational distributions in summer. Soil temperature and pH were the key factors in winter. The network analysis revealed the bacteria are better able to adapt to environmental fluctuations during the summer season. Additionally, compared to abundant bacteria, the taxonomy of rare bacteria displayed a higher degree of complexity. Our discovery contributes to advancing our comprehension of intricate dynamic diversity patterns in abundant and rare bacteria in the context of environmental gradients and seasonal fluctuations.

10.
Adv Healthc Mater ; 13(9): e2303252, 2024 04.
Article in English | MEDLINE | ID: mdl-38245866

ABSTRACT

The complex preparation, weak wet tissue adhesion, and limited biological activity of traditional oral wound dressings usually impede their efficient treatment and healing for diabetic oral mucosal defects. To overcome these problems, a novel hydrogel adhesive (named CFT hydrogel) is rapidly constructed using a one-step method based on dual-dynamic covalent cross-linking. Compared with the commercial oral patches, the CFT hydrogel shows superior in vivo (rat tongue) wet tissue adhesion performance. Additionally, the CFT hydrogel exhibits unique acid-responsive properties, thereby facilitating the release of bioactive molecule tannic acid in the acidic diabetic wound microenvironment. And a series of in vitro experiments substantiate the favorable biocompatibility and bioactivity properties (including antibacterial, antioxidative, anti-inflammatory, and angiogenetic effects) exhibited by CFT hydrogel. Moreover, in vivo experiments conducted on a diabetic rat model with oral mucosal defects demonstrate that the CFT hydrogel exhibits significant efficacy in protecting against mucosal wounds, alleviating inflammatory reactions, thereby facilitating the wound-healing process. Taken together, this study provides a promising and comprehensive therapeutic option with great potential for the clinical management of oral mucosa defects in diabetic patients.


Subject(s)
Diabetes Mellitus , Mouth Mucosa , Polyphenols , Humans , Animals , Rats , Hydrogels/pharmacology , Tannins/pharmacology , Tannins/therapeutic use , Tissue Adhesions , Anti-Bacterial Agents
11.
J Xray Sci Technol ; 32(2): 285-301, 2024.
Article in English | MEDLINE | ID: mdl-38217630

ABSTRACT

Diabetic retinopathy (DR) is one of the leading causes of blindness. However, because the data distribution of classes is not always balanced, it is challenging for automated early DR detection using deep learning techniques. In this paper, we propose an adaptive weighted ensemble learning method for DR detection based on optical coherence tomography (OCT) images. Specifically, we develop an ensemble learning model based on three advanced deep learning models for higher performance. To better utilize the cues implied in these base models, a novel decision fusion scheme is proposed based on the Bayesian theory in terms of the key evaluation indicators, to dynamically adjust the weighting distribution of base models to alleviate the negative effects potentially caused by the problem of unbalanced data size. Extensive experiments are performed on two public datasets to verify the effectiveness of the proposed method. A quadratic weighted kappa of 0.8487 and an accuracy of 0.9343 on the DRAC2022 dataset, and a quadratic weighted kappa of 0.9007 and an accuracy of 0.8956 on the APTOS2019 dataset are obtained, respectively. The results demonstrate that our method has the ability to enhance the ovearall performance of DR detection on OCT images.


Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Humans , Diabetic Retinopathy/diagnostic imaging , Bayes Theorem , Tomography, Optical Coherence/methods , Machine Learning
12.
Tree Physiol ; 44(1)2024 02 06.
Article in English | MEDLINE | ID: mdl-37847610

ABSTRACT

Leaf respiration in the light (Rlight) is crucial for understanding the net CO2 exchange of individual plants and entire ecosystems. However, Rlight is poorly quantified and rarely discussed in the context of the leaf economic spectrum (LES), especially among woody species differing in plant functional types (PFTs) (e.g., evergreen vs. deciduous species). To address this gap in our knowledge, Rlight, respiration in the dark (Rdark), light-saturated photosynthetic rates (Asat), leaf dry mass per unit area (LMA), leaf nitrogen (N) and phosphorus (P) concentrations, and maximum carboxylation (Vcmax) and electron transport rates (Jmax) of 54 representative subtropical woody evergreen and deciduous species were measured. With the exception of LMA, the parameters quantified in this study were significantly higher in deciduous species than in evergreen species. The degree of light inhibition did not significantly differ between evergreen (52%) and deciduous (50%) species. Rlight was significantly correlated with LES traits such as Asat, Rdark, LMA, N and P. The Rlight vs. Rdark and N relationships shared common slopes between evergreen and deciduous species, but significantly differed in their y-intercepts, in which the rates of Rlight were slower or faster for any given Rdark or N in deciduous species, respectively. A model for Rlight based on three traits (i.e., Rdark, LMA and P) had an explanatory power of 84.9%. These results show that there is a link between Rlight and the LES, and highlight that PFTs is an important factor in affecting Rlight and the relationships of Rlight with Rdark and N. Thus, this study provides information that can improve the next generation of terrestrial biosphere models (TBMs).


Subject(s)
Ecosystem , Plants , Photosynthesis , Respiration , Electron Transport , Plant Leaves , Trees
13.
Bioorg Chem ; 142: 106937, 2024 01.
Article in English | MEDLINE | ID: mdl-37913583

ABSTRACT

Gemcitabine (GEM) is a standard chemotherapeutic agent for patients with pancreatic cancer; however, GEM-based chemotherapy has a high rate of toxicity. A combination of GEM and active constituents from natural products may enhance its therapeutic efficacy and reduce its toxicity. This study investigated the synergistic effects of the combination of liriopesides B (LirB) from Liriope spicata var. prolifera and GEM on human pancreatic cancer cells. The results of our study showed that the combination of LirB and GEM synergistically decreased the viability of pancreatic cancer cells. The combination also caused a strong increase in apoptosis and a strong decrease in cell migration and invasion. Furthermore, LirB combined with GEM had potent inhibitory effects on pancreatic cancer stem cells (CSCs). Studies on the mechanisms of action showed that the combination more potently inhibited protein kinase B (Akt) and nuclear factor kappa B (NF-κB), as well as the downstream antiapoptotic molecules B-cell lymphoma 2 (Bcl-2) and survivin than either agent used alone. The results of this study suggest that the combination of LirB with GEM may improve the efficacy of GEM for the treatment of pancreatic cancer.


Subject(s)
Gemcitabine , Pancreatic Neoplasms , Humans , Deoxycytidine/pharmacology , Cell Line, Tumor , Pancreatic Neoplasms/pathology , NF-kappa B/metabolism , Apoptosis , Cell Proliferation
14.
Bioorg Chem ; 141: 106911, 2023 12.
Article in English | MEDLINE | ID: mdl-37832223

ABSTRACT

Drug-resistant bacterium infections are a severe threat to public health and novel antimicrobial agents combating drug-resistant bacteria are an unmet medical need. Although cannabidiol (CBD) has been reported to show antibacterial effects, whether its antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) can be improved remains unclear. Herein, a series of novel CBD derivatives were designed and synthesized using various chemical approaches including amidation, Friedel-Crafts alkylation, and Negishi cross-coupling reaction for the modifications at the C-7, C-2', C-4', and C-6' positions of CBD skeleton. Derivative 21f showed augmented antibacterial activity against MRSA with a minimum inhibitory concentration of 4 µM without cytotoxic effect in microglia BV2 cells. Further mechanistic studies suggested that 21f inhibited the formation of biofilms, induced excess reactive oxygen species, and reduced bacterial metabolism, which collectively led to the acceleration of bacterial death. Findings from this study expand the understanding of CBD derivatives as promising antibacterial agents, which provides useful information for the development of cannabinoid-based antibacterial agents.


Subject(s)
Cannabidiol , Methicillin-Resistant Staphylococcus aureus , Anti-Bacterial Agents/pharmacology , Cannabidiol/pharmacology , Microbial Sensitivity Tests , Bacteria
15.
J Phys Chem A ; 127(36): 7487-7495, 2023 Sep 14.
Article in English | MEDLINE | ID: mdl-37669444

ABSTRACT

The aromaticity of π-conjugated compounds has long been a confusing issue. Based on a recently emerged two-dimensional (2D) superatomic-molecule theory, a unified rule was built to decipher the aromaticity of cyclic superatomic molecules of π-conjugated compounds from the chemical bonding perspective. Herein, a series of planar [n]helicenes and [n]circulenes, composed of benzene, thiophene, or furfuran, are systemically studied and seen as superatomic molecules ◊On-2◊F2 or ◊On, where superatoms ◊F and ◊O denote π-conjugated units with 5 and 4 π electrons, respectively. The ascertained superatomic Lewis structures intuitively display aromaticity with each basic unit meeting the superatomic sextet rule of benzene, similar to classical valence bond theory, which is favored by the synthesized complex π-conjugated compounds comprising different numbers and kinds of subrings. The evolutionary trend of ring currents and chemical bonding suggests a local ribbon-like aromaticity in these π-conjugated compounds. Moreover, nonplanar helical π-conjugated compounds have the potential to evolve into spring-like periodic materials with excellent physical properties.

16.
J Gastroenterol ; 58(12): 1222-1236, 2023 12.
Article in English | MEDLINE | ID: mdl-37665532

ABSTRACT

BACKGROUND: Identifying past temporal trends in non-alcoholic steatohepatitis (NASH)-associated liver cancer (NALC) can increase public awareness of the disease and facilitate future policy development. METHODS: Annual deaths and age-standardized death rates (ASDR) for NALC from 1990 to 2019 were collected from the Global Burden of Disease (GBD) 2019 study. The long-term trend and the critical inflection of mortality of NALC were detected by Joinpoint analysis. Age-period-cohort analysis was employed to evaluate the effects of age, period, and cohort. Last, decomposition analysis was used to reveal the aging and population growth effects for NALC burden. RESULTS: Between 1990 and 2019, the ASDR of NALC witnessed an overall declining trend on a global scale, with a decrease in females and a stable trend in males. However, the global ASDR demonstrated a significant upward trend from 2010 to 2019. Southern sub-Saharan Africa and Southeast Asia have the highest NALC burdens, while high socio-demographic index (SDI) region experienced the fastest escalation of NALC burdens over 30 years. The decomposition analysis revealed that population growth and aging were the primary catalysts behind the increase in global NALC deaths. Age-period-cohort analyses showed that NALC mortality declined the fastest among females aged 40-45 years in high SDI region, accompanied by a deteriorating period effect trend during the period of 2010-2019. CONCLUSION: The global absolute deaths and ASDR of NALC have witnessed a rise in the past decade, with populations exhibiting considerable disparities based on sex, age, and region. Population growth, aging, and metabolism-related factors were the main factors behind the increase in global NALC deaths.


Subject(s)
Neoplasms , Non-alcoholic Fatty Liver Disease , Male , Female , Humans , Non-alcoholic Fatty Liver Disease/epidemiology , Global Health , Global Burden of Disease , Age Distribution , Cohort Studies
17.
Biotechnol Lett ; 45(10): 1327-1337, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37526868

ABSTRACT

PURPOSE: Viruses, such as Ebola virus (EBOV), evolve rapidly and threaten the human health. There is a great demand to exploit efficient gene-editing techniques for the identification of virus to probe virulence mechanism for drug development. METHODS: Based on lambda Red recombination in Escherichia coli (E. coli), counter-selection, and in vitro annealing, a high-efficiency genetic method was utilized here for precisely engineering viruses. EBOV trVLPs assay and dual luciferase reporter assay were used to further test the effect of mutations on virus replication. RESULTS: Considering the significance of matrix protein VP24 in EBOV replication, the types of mutations within vp24, including several single-base substitutions, one double-base substitution, two seamless deletions, and one targeted insertion, were generated on the multi-copy plasmid of E. coli. Further, the length of the homology arms for recombination and in vitro annealing, and the amount of DNA cassettes and linear plasmids were optimized to create a more elaborate and cost-efficient protocol than original approach. The effects of VP24 mutations on the expression of a reporter gene (luciferase) from the EBOV minigenome were determined, and results indicated that mutations of key sites within VP24 have significant impacts on EBOV replication. CONCLUSION: This precise mutagenesis method will facilitate effective and simple editing of viral genes in E. coli.


Subject(s)
Ebolavirus , Hemorrhagic Fever, Ebola , Humans , Escherichia coli/genetics , Escherichia coli/metabolism , Viral Proteins/genetics , Hemorrhagic Fever, Ebola/genetics , Ebolavirus/genetics , Ebolavirus/metabolism , Genetic Engineering , Recombination, Genetic
18.
Oecologia ; 202(4): 845-854, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37624444

ABSTRACT

Cortex radius (CR) and stele radius (SR) are important functional traits associated with the nutrient acquisition and transport functions of fine roots, respectively. However, for developmental and anatomical reasons, the resource acquisition-transport relationship of fine roots is expected to be different for different root orders. To address this issue, critical fine root anatomical traits were examined for the first three orders of roots of 59 subtropical woody plants. Designating the most distal fine roots as order one, SR scaled isometrically with respect to root radius (RR) (i.e., SR ∝ RR1.0) in the three root orders, whereas CR scaled allometrically with respect to RR (i.e., CR ∝ RR>1.0) with the numerical values of scaling exponents increasing significantly with increasing root orders thereby indicating a disproportional increase in CR with increasing root orders. There were also differences between normalized root tissue (CR/RR and SR/RR) and RR in different root orders. A negative isometric relationship (i.e., SR/RR ∝ RR-1.0) existed between SR/RR and RR in three order roots, whereas the allometric exponent between CR/RR and RR increased with root order (from 0.88 to 1.55). Collectively, the data indicate that root anatomical and functional traits change as a function of RR and that these changes need to be considered when modeling fine root resource acquisition-transport functions.

19.
Oncologist ; 28(11): e995-e1004, 2023 Nov 02.
Article in English | MEDLINE | ID: mdl-37265056

ABSTRACT

BACKGROUND: The disease burden of pancreatic cancer in East Asia is at a high level, but the epidemiological characteristics of pancreatic cancer in the region have not been systematically studied. METHOD: Joinpoint analysis was used to identify average annual percentage change (AAPC) and annual percentage change (APC) in mortality. Age-period-cohort models were used to analyze age-period cohort effects across countries. Bayesian age-period-cohort (BAPC) analysis was used to project the burden of disease for 2020-2030. RESULTS: Pancreatic cancer mortality in males in Japan (2012-2019, APC = -0.97) and Korea (2012-2019, APC = -0.91) has shown a decreasing trend since 2012 (P < .05). However, China (2016-2019, APC = 3.21), Mongolia (2015-2.019, APC = 2.37), and North Korea (2012-2019, APC = 0.47) showed a significant increase in pancreatic cancer in both genders (P < .05). Risk factors for pancreatic cancer in East Asia remained largely stable between 2010 and 2019. Mortality of pancreatic cancer due to smoking began to decline in areas with high socio-demographic index (SDI), and mortality of pancreatic cancer due to high body mass index and high fasting plasma glucose increased with SDI. The age-standardized mortality for pancreatic cancer in Chinese males is expected to exceed that of Japan and South Korea by 2030, but the disease burden of pancreatic cancer in Japan and South Korea remains at extremely high levels. CONCLUSION: Economically developed countries are beginning to show a decreasing trend in the burden of pancreatic cancer disease, and developing countries are experiencing a rapid increase in the age-standardized death rate (ASDR) of pancreatic cancer.


Subject(s)
Pancreatic Neoplasms , Female , Humans , Male , Bayes Theorem , Asia, Eastern , Japan , Risk Factors , Quality-Adjusted Life Years
20.
Biotechnol J ; 18(10): e2200582, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37357718

ABSTRACT

BACKGROUND: Mussel foot proteins (Mfps) are considered as remarkable materials due to their extraordinary adhesive capability. Recombinant expression is an ideal way to synthesis these proteins at large scale. However, secretory expression of Mfps into culture medium has not been achieved in a heterologous host. METHODS AND RESULTS: Here, to realize the secretion of Mfp3 and Mfp5 in Bacillus subtilis, signal peptide screening was first performed. Minimal Mfp3-6×His was targeted into the growth medium with AmyE signal peptide. We found that a small chaperone protein Spy was secreted efficiently in B. subtilis, and the fusion proteins Spy-Mfp3-6×His and Spy-Mfp5-6×His could also be delivered into growth medium well. The yield of Spy-Mfp3-6×His and Spy-Mfp5-6×His reached 255 and 119 mg L-1 at shake flask conditions, respectively. Mfp3-6×His and Mfp5-6×His were finally purified via TEV protease cleavage and NTA affinity chromatography. CONCLUSION: Mfp3-6×His and Mfp5-6×His could be efficiently secreted using a chaperone protein Spy as fusion tag in B. subtilis.

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