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1.
Mol Biol Rep ; 51(1): 546, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38642246

ABSTRACT

Breast cancer is a leading cause of mortality and the most prevalent form of malignant tumor among women worldwide. Breast cancer cells exhibit an elevated glycolysis and altered glucose metabolism. Moreover, these cells display abnormal glycosylation patterns, influencing invasion, proliferation, metastasis, and drug resistance. Consequently, targeting glycolysis and mitigating abnormal glycosylation represent key therapeutic strategies for breast cancer. This review underscores the importance of protein glycosylation and glucose metabolism alterations in breast cancer. The current research efforts in developing effective interventions targeting glycolysis and glycosylation are further discussed.


Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/metabolism , Glycosylation , Glycolysis , Glucose/metabolism , Cell Line, Tumor , Cell Proliferation
2.
Elife ; 122024 Apr 03.
Article in English | MEDLINE | ID: mdl-38567911

ABSTRACT

The antibiotic heliomycin (resistomycin), which is generated from Streptomyces resistomycificus, has multiple activities, including anticancer effects. Heliomycin was first described in the 1960s, but its clinical applications have been hindered by extremely low solubility. A series of 4-aminomethyl derivatives of heliomycin were synthesized to increase water solubility; studies showed that they had anti-proliferative effects, but the drug targets remained unknown. In this study, we conducted cellular thermal shift assays (CETSA) and molecular docking simulations to identify and validate that heliomycin and its water-soluble derivative, 4-(dimethylaminomethyl)heliomycin (designated compound 4-dmH) engaged and targeted with sirtuin-1 (SIRT1) in p53-functional SAS and p53-mutated HSC-3 oral cancer cells. We further addressed the cellular outcome of SIRT1 inhibition by these compounds and found that, in addition to SIRT1, the water-soluble 4-dmH preferentially targeted a tumor-associated NADH oxidase (tNOX, ENOX2). The direct binding of 4-dmH to tNOX decreased the oxidation of NADH to NAD+ which diminished NAD+-dependent SIRT1 deacetylase activity, ultimately inducing apoptosis and significant cytotoxicity in both cell types, as opposed to the parental heliomycin-induced autophagy. We also observed that tNOX and SIRT1 were both upregulated in tumor tissues of oral cancer patients compared to adjacent normal tissues, suggesting their clinical relevance. Finally, the better therapeutic efficacy of 4-dmH was confirmed in tumor-bearing mice, which showed greater tNOX and SIRT1 downregulation and tumor volume reduction when treated with 4-dmH compared to heliomycin. Taken together, our in vitro and in vivo findings suggest that the multifaceted properties of water-soluble 4-dmH enable it to offer superior antitumor value compared to parental heliomycin, and indicated that it functions through targeting the tNOX-NAD+-SIRT1 axis to induce apoptosis in oral cancer cells.


Subject(s)
Mouth Neoplasms , Polycyclic Compounds , Sirtuin 1 , Humans , Animals , Mice , Sirtuin 1/metabolism , Cell Line, Tumor , NAD/metabolism , Tumor Suppressor Protein p53/metabolism , Molecular Docking Simulation , Apoptosis , Mouth Neoplasms/drug therapy
3.
Plant Physiol ; 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38497551

ABSTRACT

Root hairs (RHs), extensive structures of root epidermal cells, are important for plant nutrient acquisition, soil anchorage, and environmental interactions. Excessive production of the phytohormone ethylene (ET) leads to substantial root hair growth, manifested as tolerance to plant nutrient deficiencies. However, the molecular basis of ET production during root hair growth in response to nutrient starvation remains unknown. Herein, we found that a critical transcription factor, GLABRA 2 (GL2), inhibits ET production during root hair growth in Arabidopsis (Arabidopsis thaliana). GL2 directly binds to the promoter of the gene encoding ET OVERPRODUCER 1 (ETO1), one of the most important ET-production-regulation factors, in vitro and in vivo, and then regulates the accumulation and function of ETO1 in root hair growth. The GL2-regulated-ETO1 module is required for promoting root hair growth under nitrogen, phosphorus, or potassium deficiency. Genome-wide analysis revealed numerous genes, such as ROOT HAIR DEFECTIVE 6-LIKE 4, ETHYLENE-INSENSITIVE 3-LIKE 2, ROOT HAIR SPECIFIC 13, are involved in the GL2-regulated-ETO1 module. Our work reveals a key transcription mechanism in the control of ET production during root hair growth under three major nutrient deficiencies.

4.
Cells ; 13(5)2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38474377

ABSTRACT

Immunotherapy has emerged as a promising new treatment modality for head and neck cancer, offering the potential for targeted and effective cancer management. Squamous cell carcinomas pose significant challenges due to their aggressive nature and limited treatment options. Conventional therapies such as surgery, radiation, and chemotherapy often have limited success rates and can have significant side effects. Immunotherapy harnesses the power of the immune system to recognize and eliminate cancer cells, and thus represents a novel approach with the potential to improve patient outcomes. In the management of head and neck squamous cell carcinoma (HNSCC), important contributions are made by immunotherapies, including adaptive cell therapy (ACT) and immune checkpoint inhibitor therapy. In this review, we are focusing on the latter. Immune checkpoint inhibitors target proteins such as programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) to enhance the immune response against cancer cells. The CTLA-4 inhibitors, such as ipilimumab and tremelimumab, have been approved for early-stage clinical trials and have shown promising outcomes in terms of tumor regression and durable responses in patients with advanced HNSCC. Thus, immune checkpoint inhibitor therapy holds promise in overcoming the limitations of conventional therapies. However, further research is needed to optimize treatment regimens, identify predictive biomarkers, and overcome potential resistance mechanisms. With ongoing advancements in immunotherapy, the future holds great potential for transforming the landscape of oral tumor treatment and providing new hope for patients.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Humans , Squamous Cell Carcinoma of Head and Neck , Immune Checkpoint Inhibitors , Immunotherapy/adverse effects , Carcinoma, Squamous Cell/etiology
5.
Sci Robot ; 9(88): eadi5155, 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38478591

ABSTRACT

Wireless millimeter-scale robots capable of navigating through fluid-flowing tubular structures hold substantial potential for inspection, maintenance, or repair use in nuclear, industrial, and medical applications. However, prevalent reliance on external powering constrains these robots' operational range and applicable environments. Alternatives with onboard powering must trade off size, functionality, and operation duration. Here, we propose a wireless millimeter-scale wheeled robot capable of using environmental flows to power and actuate its long-distance locomotion through complex pipelines. The flow-powering module can convert flow energy into mechanical energy, achieving an impeller speed of up to 9595 revolutions per minute, accompanied by an output power density of 11.7 watts per cubic meter and an efficiency of 33.7%. A miniature gearbox module can further transmit the converted mechanical energy into the robot's locomotion system, allowing the robot to move against water flow at an average rate of up to 1.05 meters per second. The robot's motion status (moving against/with flow or pausing) can be switched using an external magnetic field or an onboard mechanical regulator, contingent on different proposed control designs. In addition, we designed kirigami-based soft wheels for adaptive locomotion. The robot can move against flows of various substances within pipes featuring complex geometries and diverse materials. Solely powered by flow, the robot can transport cylindrical payloads with a diameter of up to 55% of the pipe's diameter and carry devices such as an endoscopic camera for pipeline inspection, a wireless temperature sensor for environmental temperature monitoring, and a leak-stopper shell for infrastructure maintenance.

6.
Cardiovasc Diabetol ; 23(1): 79, 2024 02 24.
Article in English | MEDLINE | ID: mdl-38402392

ABSTRACT

BACKGROUND: Insulin resistance (IR) is associated with coronary artery disease (CAD) severity. However, its underlying mechanisms are not fully understood. Therefore, our study aimed to explore the relationship between IR and coronary inflammation and investigate the synergistic and mediating effects of coronary inflammation on the association between IR and CAD severity. METHODS: Consecutive patients with CAD who underwent coronary angiography and coronary computed tomography angiography between April 2018 and March 2023 were enrolled. The triglyceride-glucose index (TyG index) and peri-coronary adipose tissue (PCAT) attenuation around the proximal right coronary artery (RCA) were used to evaluate IR and coronary inflammation, respectively. The correlation between the TyG index and PCAT attenuation was analyzed using linear regression models. Logistic regression models were further used for investigating the correlation of the TyG index and PCAT attenuation with CAD severity. A mediation analysis assessed the correlation between IR and CAD severity mediated by coronary inflammation. RESULTS: A total of 569 participants (mean age, 62 ± 11 years; 67.8% men) were included in the study. PCAT attenuation was positively associated with the TyG index (r = 0.166; P < 0.001). After adjusting for potential confounders, the per standard deviation increment in the TyG index was associated with a 1.791 Hounsfield unit (HU) increase (95% confidence interval [CI], 0.920-2.662 HU; P < 0.001) in the PCAT attenuation. In total, 382 (67.1%) patients had multivessel CAD. The patients in the high-TyG index/high PCAT attenuation group had approximately 3.2 times the odds of multivessel CAD compared with those in the low-TyG index/low PCAT attenuation group (odds ratio, 3.199; 95%CI, 1.826-5.607; P < 0.001). Mediation analysis indicated that PCAT attenuation mediated 31.66% of the correlation between the TyG index and multivessel CAD. CONCLUSIONS: The TyG index positively correlated with PCAT attenuation in patients with CAD. The TyG index and PCAT attenuation showed a synergistic correlation with multivessel CAD. Furthermore, PCAT attenuation partially mediated the relationship between the TyG index and CAD severity. Controlling inflammation in patients with high IR and coronary inflammation may provide additional benefits.


Subject(s)
Coronary Artery Disease , Insulin Resistance , Male , Humans , Middle Aged , Aged , Female , Coronary Artery Disease/diagnostic imaging , Cross-Sectional Studies , Coronary Angiography/methods , Glucose , Arrhythmias, Cardiac , Inflammation/diagnostic imaging
7.
Healthcare (Basel) ; 12(1)2024 Jan 03.
Article in English | MEDLINE | ID: mdl-38201018

ABSTRACT

BACKGROUND: Metabolic syndrome (MetS) is a prevalent health condition in Taiwan that places individuals at higher risk of cardiovascular disease, diabetes, and stroke. Therefore, the identification of risk factors associated with MetS is crucial. The aim of this study was to investigate the association of uric acid and MetS in a Taiwanese community with a middle-aged and elderly population. METHODS: This cross-sectional study enrolled residents aged 50-90 years living in one community. All of the subjects received a standardized personal interview, including a structured questionnaire, anthropometric measurements, and blood samples were collected for laboratory testing. MetS was defined as excess waist circumference, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL). Multiple logistic regression models were used to evaluate uric acid tertiles associated with MetS. RESULTS: A total of 400 subjects were enrolled in the analysis. The overall prevalence of MetS was 35.8%. The prevalence of MetS increased gradually with increasing serum uric acid levels (p value < 0.001). A significant association between uric acid and cardiometabolic risk factors was confirmed, with a Pearson's correlation coefficient for waist circumference of 0.30 (p < 0.001), a coefficient for systolic blood pressure of 0.13 (p = 0.01), a coefficient for triglycerides of 0.33 (p < 0.001), and a coefficient for high-density lipoprotein of -0.30 (p < 0.001). The adjusted odds ratio (OR) of the high uric acid tertile level for MetS was 2.48 (95% CI = 1.31-4.71, p = 0.01). The area under the ROC curve (AUC) for uric acid in predicting MetS was 0.621 (p < 0.001). CONCLUSIONS: The prevalence of MetS in our study population is high. High serum uric acid levels are independently associated with the presence of MetS among the middle-aged and elderly Taiwanese population.

8.
Diabetes Metab Syndr Obes ; 17: 131-142, 2024.
Article in English | MEDLINE | ID: mdl-38222031

ABSTRACT

Introduction: Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common chronic liver disease, which is usually associated with type 2 diabetes mellitus (T2DM) and obesity. However, the incidence of MALFD in non-obese individuals without T2DM is increasing, and the pathogenesis is unclear. Serum uric acid to creatinine ratio (sUA/Cr) can reflect overall metabolic status. This study aims to observe the association between sUA/Cr and MAFLD in non-obese individuals without T2DM. Methods: A total of 21,996 individuals were included in this study. The subjects were divided into four subgroups: non-obese patients without T2DM, obese patients without T2DM, non-obese patients with T2DM, and obese patients with T2DM. Logistic regression analyzed the correlation between sUA/Cr and MAFLD subgroups. Receiver operating characteristics analyzed the predictive value of sUA/Cr for MAFLD subgroups. The stratified analyses by sex and age were performed. Results: Non-obese MAFLD individuals without T2DM had higher sUA/Cr levels than their counterparts. sUA/Cr was significantly correlated positively with MAFLD in non-obese patients. Similar results were observed in both males and females and in populations at all age stages (all p<0.01). sUA/Cr was capable of discriminating MAFLD in non-obese individuals without T2DM (AUC: 0.667), especially for patients over 60 years old (AUC: 0.704). Conclusion: The sUA/Cr ratio was correlated with MAFLD in non-obese patients without T2DM. The predictive value of sUA/Cr for MAFLD was observed. Hence, the sUA/Cr ratio might be given more concern for the risk of MAFLD in non-obese individuals without T2DM.

10.
Int Urol Nephrol ; 56(2): 625-633, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37450242

ABSTRACT

PURPOSE: We undertook a multicenter epidemiological survey among hospitalized patients with chronic kidney disease (CKD), aiming to reveal the characteristics of elderly CKD by comparing it with non-elderly CKD. METHODS: Medical records were obtained from 18 military hospitals across China from 1 January 2009 to 31 December 2011. The characteristics of chronic kidney disease in the elderly were analyzed through comparing with those in younger patients with chronic kidney disease. RESULTS: A total of 380,461 hospitalized patients were included in the database, with 25,826 (6.8%) diagnosed with CKD. Unlike non-elderly, the top-three causes of chronic kidney disease among elderly patients were diabetic nephropathy (24.1%), hypertension-related renal impairment (20.9%), and primary glomerular disease (11.1%). 71.6% of the elderly patients with CKD had more than one comorbidities and the number of morbidities increased with age. In-hospital mortality of the elderly was significantly higher than those of younger patients (3.3% vs. 1.0%). Multiple logistic regression analysis showed that age, CKD 5 stage, acidosis, cardiovascular and cerebrovascular diseases, infection disease, neoplasm, and dementia were independent risk factors for death from CKD in the elderly. The median length of stay (LOS) was similar between elderly and younger CKD patients. The median cost was higher for elderly CKD patients than for younger CKD patients. Among elderly individuals with CKD, LOS, and hospitalization costs also increased with an increase in the number of coexisting diseases. CONCLUSIONS: Diabetic nephropathy,  and hypertension-related kidney injury were the leading causes of chronic kidney disease in elderly patients, which is different from the non-elderly. Elderly patients with chronic kidney disease were more likely to have a higher burden of comorbidities, which were associated with worse in-hospital outcomes.


Subject(s)
Diabetic Nephropathies , Hypertension , Renal Insufficiency, Chronic , Humans , Aged , Middle Aged , Cross-Sectional Studies , Diabetic Nephropathies/complications , Glomerular Filtration Rate , Renal Insufficiency, Chronic/complications , Hypertension/complications , Risk Factors
11.
Life (Basel) ; 13(10)2023 Oct 14.
Article in English | MEDLINE | ID: mdl-37895439

ABSTRACT

This study intends to assess the analgesic effects, physical facilitation, and safety of willow bark use in patients with arthritis. Our study was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. PubMed, Scopus, EMBASE, Web of Science, Cochrane, and ClinicalTrials.gov were searched for relative randomized controlled trials (RCTs) describing the efficacy or adverse events of willow bark in patients with arthritis until 12 April 2023. We used Cochrane ROB 2.0 and the Grading of Recommendations, Assessment, Development, and Evaluations system to evaluate the quality of studies and evidence. The meta-analysis was carried out by the fix-effects model. This study included five studies with six RCTs consisting of 329 patients with arthritis. The results showed significant differences in pain relief and improvement in physical status for patients with arthritis between willow bark treatment and placebo groups, and no significant differences in the risk of all adverse events in patients with arthritis between willow bark treatment and placebo. Owing to the potential bias, the certainty and evidence of our findings are still inadequate. Therefore, further RCTs are needed to confirm our results.

12.
Diagnostics (Basel) ; 13(18)2023 Sep 21.
Article in English | MEDLINE | ID: mdl-37761383

ABSTRACT

BACKGROUND: Numerous mortality prediction tools are currently available to assist patients with moderate to severe traumatic brain injury (TBI). However, an algorithm that utilizes various machine learning methods and employs diverse combinations of features to identify the most suitable predicting outcomes of brain injury patients in the intensive care unit (ICU) has not yet been well-established. METHOD: Between January 2016 and December 2021, we retrospectively collected data from the electronic medical records of Chi Mei Medical Center, comprising 2260 TBI patients admitted to the ICU. A total of 42 features were incorporated into the analysis using four different machine learning models, which were then segmented into various feature combinations. The predictive performance was assessed using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve and validated using the Delong test. RESULT: The AUC for each model under different feature combinations ranged from 0.877 (logistic regression with 14 features) to 0.921 (random forest with 22 features). The Delong test indicated that the predictive performance of the machine learning models is better than that of traditional tools such as APACHE II and SOFA scores. CONCLUSION: Our machine learning training demonstrated that the predictive accuracy of the LightGBM is better than that of APACHE II and SOFA scores. These features are readily available on the first day of patient admission to the ICU. By integrating this model into the clinical platform, we can offer clinicians an immediate prognosis for the patient, thereby establishing a bridge for educating and communicating with family members.

13.
JASA Express Lett ; 3(6)2023 Jun 01.
Article in English | MEDLINE | ID: mdl-37289171

ABSTRACT

For a narrowband signal, an oscillating interference pattern is formed with a target's moving when receiving at the bottom of the sea. In this Letter, the interference pattern of a narrowband source is observed using a single vector sensor (SVS). A passive depth estimation method employing a SVS is proposed. This approach processes the signals after the adaptive line enhancing and extracts the vector intensity, which oscillates periodically with the vertical azimuth. The passive estimation is achieved based on the Fourier-transform relationship between the depth and interference period. The simulation and sea experiment verify this method.


Subject(s)
Acoustics , Water , Computer Simulation , Fourier Analysis
14.
Am J Physiol Endocrinol Metab ; 325(1): E62-E71, 2023 07 01.
Article in English | MEDLINE | ID: mdl-37285598

ABSTRACT

According to the latest consensus statement, fatty liver complicated by specific metabolic abnormalities can be diagnosed as metabolic dysfunction-associated fatty liver disease (MAFLD) in nonobese patients without type 2 diabetes mellitus (T2DM). However, hyperuricemia (HUA), a manifestation of metabolic disorders, is excluded from diagnostic criteria. This study explored the association between HUA and MAFLD in nonobese patients without T2DM. A total of 28,187 participants were recruited from the Examination Center of the China-Japan Friendship Hospital from 2018 to 2022 and divided into four subgroups: nonobese patients without T2DM, obese patients without T2DM, nonobese patients with T2DM, and obese patients with T2DM. MAFLD was diagnosed by ultrasound combined with laboratory examinations. The association of HUA with MAFLD subgroups was performed by logistical regression analysis. The predictive ability of UA for MAFLD subgroups was assessed by receiver operating characteristics (ROC). HUA was positively associated with MAFLD in nonobese patients without T2DM in both males and females, even after adjusting for sex, BMI, dyslipidemia, and abnormal liver function. The association increased gradually with aging, especially in those over 40 yr old. HUA was an independent risk factor for MAFLD in nonobese patients without T2DM. We suggest that UA abnormalities might be considered in the diagnosis of MAFLD in nonobese patients without T2DM.NEW & NOTEWORTHY HUA is an independent risk factor for MAFLD in nonobese patients without T2DM. The association of HUA with MAFLD in nonobese patients without T2DM increased gradually with aging, especially in those over 40 yr old. In nonobese patients without T2DM, univariate analysis showed that females with HUA had a higher risk of MAFLD than males. However, the difference was narrowed after adjustment for confounders.


Subject(s)
Diabetes Mellitus, Type 2 , Hyperuricemia , Non-alcoholic Fatty Liver Disease , Female , Male , Humans , Diabetes Mellitus, Type 2/complications , Hyperuricemia/complications , Risk Factors , Obesity/complications
15.
J Cachexia Sarcopenia Muscle ; 14(4): 1855-1864, 2023 08.
Article in English | MEDLINE | ID: mdl-37300354

ABSTRACT

BACKGROUND: Frailty and sarcopenia are prevalent in chronic kidney disease (CKD) populations and could increase the risk for adverse health outcomes. Few studies assess the correlation between frailty, sarcopenia and CKD in non-dialysis patients. Therefore, this study aimed to determine frailty-associated factors in elderly CKD stage I-IV patients, expected to early identify and intervene in the frailty of elderly CKD patients. METHODS: A total of 774 elderly CKD I-IV patients (>60 years of age) recruited from 29 clinical centers in China between March 2017 and September 2019 were included in this study. We established a Frailty Index (FI) model to evaluate frailty risk and verified the distributional property of FI in the study population. Sarcopenia was defined according to the criteria of the Asian Working Group for Sarcopenia 2019. Multinomial logistic regression analysis was used to assess the associated factors for frailty. RESULTS: Seven hundred seventy-four patients (median age 67 years, 66.0% males) were included in this analysis, with a median estimated glomerular filtration rate of 52.8 mL/min/1.73 m2 . The prevalence of sarcopenia was 30.6%. The FI exhibited a right-skewed distribution. The age-related slope of FI was 1.4% per year on a logarithmic scale (r2  = 0.706, 95% CI 0.9, 1.8, P < 0.001). The upper limit of FI was around 0.43. The FI was related to mortality (HR = 1.06, 95% CI 1.00, 1.12, P = 0.041). Multivariate multinomial logistic regression analysis showed that sarcopenia, advanced age, CKD stage II-IV, low level of serum albumin and increased waist-hip ratio were significantly associated with high FI status, while advanced age and CKD stage III-IV were significantly associated with for median FI status. Moreover, the results from the subgroup were consistent with the leading results. CONCLUSIONS: Sarcopenia was independently associated with an increased risk for frailty in elderly CKD I-IV patients. Patients with sarcopenia, advanced age, high CKD stage, high waist-hip ratio and low serum albumin level should be assessed for frailty.


Subject(s)
Frailty , Renal Insufficiency, Chronic , Sarcopenia , Male , Humans , Aged , Female , Frailty/epidemiology , Sarcopenia/etiology , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/epidemiology , Glomerular Filtration Rate , Prevalence
16.
Molecules ; 28(9)2023 Apr 26.
Article in English | MEDLINE | ID: mdl-37175152

ABSTRACT

Versican is a chondroitin sulfate proteoglycan (CSPG), which deposits in perineurium as a physical barrier and prevents the growth of axons out of the fascial boundary. Several studies have indicated that the chondroitin sulfate (CS) chains on versican have several possible functions beyond the physical barrier, including the ability to stabilize versican core protein in the extracellular matrix. As chondroitin sulfate synthase 1 (Chsy1) is a crucial enzyme for CS elongation, we hypothesized that in vivo knockdown of Chsy1 at peripheral nerve lesion site may decrease CS and versican accumulation, and result in accelerating neurite regeneration. In the present study, end-to-side neurorrhaphy (ESN) in Wistar rats was used as an in vivo model of peripheral nerve injury to evaluate nerve regeneration after surgical intervention. The distribution and expression of versican and Chsy1 in regenerating axons after ESN was studied using confocal microscopy and western blotting. Chsy1 was silenced at the nerve lesion (surgical) site using in vivo siRNA transfection. The results indicated that Chsy1 was successfully silenced in nerve tissue, and its downregulation was associated with functional recovery of compound muscle action potential. Silencing of Chsy1 also decreased the accumulation of versican core protein, suggesting that transient treating of Chsy1-siRNA may be an alternative and an effective strategy to promote injured peripheral nerve regeneration.


Subject(s)
Chondroitin Sulfates , Versicans , Rats , Animals , Versicans/genetics , Chondroitin Sulfates/pharmacology , Rats, Wistar , Axons/metabolism , Nerve Regeneration , RNA, Small Interfering/pharmacology
17.
PNAS Nexus ; 2(5): pgad127, 2023 May.
Article in English | MEDLINE | ID: mdl-37143866

ABSTRACT

Modeling the global dynamics of emerging infectious diseases (EIDs) like COVID-19 can provide important guidance in the preparation and mitigation of pandemic threats. While age-structured transmission models are widely used to simulate the evolution of EIDs, most of these studies focus on the analysis of specific countries and fail to characterize the spatial spread of EIDs across the world. Here, we developed a global pandemic simulator that integrates age-structured disease transmission models across 3,157 cities and explored its usage under several scenarios. We found that without mitigations, EIDs like COVID-19 are highly likely to cause profound global impacts. For pandemics seeded in most cities, the impacts are equally severe by the end of the first year. The result highlights the urgent need for strengthening global infectious disease monitoring capacity to provide early warnings of future outbreaks. Additionally, we found that the global mitigation efforts could be easily hampered if developed countries or countries near the seed origin take no control. The result indicates that successful pandemic mitigations require collective efforts across countries. The role of developed countries is vitally important as their passive responses may significantly impact other countries.

18.
Med Phys ; 50(11): 7039-7048, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37219842

ABSTRACT

BACKGROUND: Single-shot balanced steady-state free precession (bSSFP) sequence is widely used in cardiac imaging. However, the limited scan time in one heartbeat greatly hinders its spatial resolution compared to the segmented acquisition mode. Therefore, a highly accelerated single-shot bSSFP imaging technology is needed for clinical use. PURPOSE: To develop and evaluate a wave-encoded bSSFP sequence with high acceleration rates for single-shot myocardial imaging. METHODS: The proposed Wave-bSSFP method is implemented by adding a sinusoidal wave gradient in the phase encoding direction during the readout of bSSFP sequence. Uniform undersampling is used for acceleration. Its performance was first validated via phantom studies by comparison with conventional bSSFP. Then it was evaluated in volunteer studies via anatomical imaging, T2 -prepared bSSFP, and T1 mapping in in-vivo cardiac imaging. All methods were compared with accelerated conventional bSSFP reconstructed using iterative SENSE and compressed sensing (CS), to demonstrate the advantage of wave encoding in suppressing the noise amplification and artifacts induced by acceleration. RESULTS: The proposed Wave-bSSFP method achieved a high acceleration factor of 4 for single-shot acquisitions. The proposed method showed lower average g-factors than bSSFP, and fewer blurring artifacts than CS reconstruction. The Wave-bSSFP with R = 4 achieved higher spatial and temporal resolutions compared with the conventional bSSFP with R = 2 in several applications such as T2 -prepared bSSFP and T1 mapping, and could be applied in systolic imaging. CONCLUSION: Wave encoding can be used to highly accelerate 2D bSSFP imaging with single-shot acquisitions. Compared with the conventional bSSFP sequence, the proposed Wave-bSSFP method can effectively reduce the g-factor and aliasing artifacts in cardiac imaging.


Subject(s)
Image Interpretation, Computer-Assisted , Tomography, X-Ray Computed , Humans , Image Interpretation, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Heart/diagnostic imaging , Artifacts
19.
Int J Mol Sci ; 24(6)2023 Mar 09.
Article in English | MEDLINE | ID: mdl-36982299

ABSTRACT

Leaf flattening plays a vital role in the establishment of plant architecture, which is closely related to plant photosynthesis and, thus, influences the product yield and quality of Chinese cabbage. In this study, we used the doubled haploid line 'FT' of Chinese cabbage as the wild type for ethyl methanesulfonate (EMS) mutagenesis and obtained a mutant cwm with stably inherited compact and wrinkled leaves. Genetic analysis revealed that the mutated trait was controlled by a single recessive nuclear gene, Brcwm. Brcwm was preliminarily mapped to chromosome A07 based on bulked segregant RNA sequencing (BSR-seq) and fine-mapped to a 205.66 kb region containing 39 genes between Indel12 and Indel21 using SSR and Indel analysis. According to the whole-genome re-sequencing results, we found that there was only one nonsynonymous single nucleotide polymorphism (SNP) (C to T) within the target interval on exon 4 of BraA07g021970.3C, which resulted in a proline to serine amino acid substitution. The mutated trait co-segregated with the SNP. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) revealed that BraA07g021970.3C expression was dramatically higher in 'FT' leaves than that in cwm leaves. BraA07g021970.3C is homologous to AT3G55000 encoding a protein related to cortical microtubule organization. A similar phenotype of dwarfism and wrinkled leaves was observed in the recessive homozygous mutant cwm-f1 of AT3G55000, and its T3 transgenic lines were restored to the Arabidopsis wild-type phenotype through ectopic overexpression of BraA07g021970.3C. These results verified that BraA07g021970.3C was the target gene essential for leaf flattening in Chinese cabbage.


Subject(s)
Brassica rapa , Brassica , Brassica rapa/genetics , Brassica rapa/metabolism , Brassica/genetics , Plant Leaves/genetics , Plant Leaves/metabolism , Mutation , Photosynthesis , Gene Expression Regulation, Plant , Plant Proteins/genetics , Plant Proteins/metabolism
20.
Int J Mol Sci ; 24(6)2023 Mar 16.
Article in English | MEDLINE | ID: mdl-36982748

ABSTRACT

Actin filaments are essential for plant adaptation to high temperatures. However, the molecular mechanisms of actin filaments in plant thermal adaptation remain unclear. Here, we found that the expression of Arabidopsis actin depolymerization factor 1 (AtADF1) was repressed by high temperatures. Compared with wild-type seedlings (WT), the mutation of AtADF1 and the overexpression of AtADF1 led to promoted and inhibited plant growth under high temperature conditions, respectively. Further, high temperatures induced the stability of actin filaments in plants. Compared with WT, Atadf1-1 mutant seedlings showed more stability of actin filaments under normal and high temperature conditions, while the AtADF1 overexpression seedlings showed the opposite results. Additionally, AtMYB30 directly bound to the promoter of AtADF1 at a known AtMYB30 binding site, AACAAAC, and promoted the transcription of AtADF1 under high temperature treatments. Genetic analysis further indicated that AtMYB30 regulated AtADF1 under high temperature treatments. Chinese cabbage ADF1 (BrADF1) was highly homologous with AtADF1. The expression of BrADF1 was inhibited by high temperatures. BrADF1 overexpression inhibited plant growth and reduced the percentage of actin cable and the average length of actin filaments in Arabidopsis, which were similar to those of AtADF1 overexpression seedlings. AtADF1 and BrADF1 also affected the expression of some key heat response genes. In conclusion, our results indicate that ADF1 plays an important role in plant thermal adaptation by blocking the high-temperature-induced stability of actin filaments and is directly regulated by MYB30.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Arabidopsis/metabolism , Actins/genetics , Actins/metabolism , Arabidopsis Proteins/metabolism , Actin Depolymerizing Factors/genetics , Actin Depolymerizing Factors/metabolism , Actin Cytoskeleton/genetics , Actin Cytoskeleton/metabolism , Seedlings/genetics , Seedlings/metabolism , Gene Expression Regulation, Plant , Transcription Factors/genetics , Transcription Factors/metabolism
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