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2.
Front Public Health ; 12: 1388831, 2024.
Article En | MEDLINE | ID: mdl-38699414

Objective: The aim of this study is to understand the job burnout of village doctors during the COVID-19 epidemic and its influencing factors, and to provide a reference for effectively alleviating the job burnout of village doctors. Methods: A cross-sectional survey was conducted among village doctors in S province in December 2021. The survey included a general information questionnaire and the CMBI Burnout Scale. Epidata was used for dual input, and descriptive analysis, t-test, chi-square test, and binary Logistic regression for statistical analysis were used. Results: A total of 993 village doctors participated in the survey. Most of them were male village doctors (62.84%), with an average age of 46.57 (SD = 7.50). Village doctors believed that the impact of the epidemic on work was serious, with a score of 3.87 ± 0.91. The economic support was small, with a score of 2.31 ± 0.99. The development space was low, with a score of 2.62 ± 0.98. The overall incidence of burnout was 53.47%. In the burnout group, 54.05% were mild, 33.14% were moderate, and 12.81% were severe. The high degree of difficulty in using WeChat (OR = 1.436, 95%CI: 1.229-1.679), high work pressure (OR = 1.857, 95%CI: 1.409-2.449), high risk of practice (OR = 1.138, 95%CI: 1.004-1.289), less economic support (OR = 0.825, 95%CI: 0.684-0.995), less technical support (OR = 0.696, 95%CI: 0.565-0.858), and poor emotional support (OR = 0.632, 95%CI: 0.513-0.780) were more likely to have job burnout. Conclusion: Burnout is a common phenomenon among village doctors during the COVID-19 pandemic, which needs to be prevented and alleviated by various measures.


Burnout, Professional , COVID-19 , Physicians , Humans , COVID-19/epidemiology , COVID-19/psychology , Burnout, Professional/epidemiology , Burnout, Professional/psychology , Cross-Sectional Studies , Male , Female , Middle Aged , Adult , Surveys and Questionnaires , Physicians/psychology , Physicians/statistics & numerical data , China/epidemiology , SARS-CoV-2 , Pandemics
3.
BMC Prim Care ; 25(1): 133, 2024 Apr 25.
Article En | MEDLINE | ID: mdl-38664696

BACKGROUND: Village doctors are the main health service providers in China's rural areas. Compared with other rural groups, they will have a sense of relative deprivation, which has an impact on their practice mentality and job stability. This study aims to analyze the changes and causes of relative deprivation among village doctors, so as to improve the stability of them. METHODS: The data were collected from two surveys conducted in Shandong Province in 2015 and 2021. In 2015, 322 village doctors were surveyed and 307 questionnaires were collected, with a recovery rate of 95.3%. In 2021, 394 village doctors were surveyed and 366 questionnaires were collected, with a recovery rate of 92.9%. Descriptive and univariate analysis were used to compare the changes before and after the survey. RESULTS: The scores of vertical deprivation of village doctors increased from 2.77 ± 0.81 in 2015 to 3.04 ± 0.83 in 2021, with a statistically significant difference (P < 0.001). The reference group selected by village doctors changed from village teachers to ordinary villagers. Compared to village teachers, the horizontal deprivation score of village doctors increased from 3.47 ± 0.87 to 3.97 ± 0.77, with a statistically significant difference (P < 0.001). Compared to villagers, only the professional reputation deprivation score increased, from 2.38 ± 0.93 to 2.68 ± 0.76, with a statistically significant difference (P < 0.05). CONCLUSIONS: As time goes by, village doctors fail to reach the expected level in terms of economic income, social status, professional reputation and living standards, resulting in a sense of relative deprivation. This may have a negative impact on village doctors' work motivation and behavior, and will fail to guarantee the sustainability of the team. We should pay attention to this unbalanced mentality of village doctors.


Physicians , Humans , Cross-Sectional Studies , China/epidemiology , Female , Male , Adult , Physicians/psychology , Physicians/statistics & numerical data , Surveys and Questionnaires , Middle Aged , Job Satisfaction , Community Health Workers , Rural Health Services/statistics & numerical data , Rural Population/statistics & numerical data
4.
Adv Sci (Weinh) ; : e2307129, 2024 Mar 17.
Article En | MEDLINE | ID: mdl-38493497

Recently mapped transcriptomic landscapes reveal the extent of heterogeneity in cancer-associated fibroblasts (CAFs) beyond previously established single-gene markers. Functional analyses of individual CAF subsets within the tumor microenvironment are critical to develop more accurate CAF-targeting therapeutic strategies. However, there is a lack of robust preclinical models that reflect this heterogeneity in vitro. In this study, single-cell RNA sequencing datasets acquired from head and neck squamous cell carcinoma tissues to predict microenvironmental and cellular features governing individual CAF subsets are leveraged. Some of these features are then incorporated into a tunable hyaluronan-based hydrogel system to culture patient-derived CAFs. Control over hydrogel degradability and integrin adhesiveness enabled derivation of the predominant myofibroblastic and inflammatory CAF subsets, as shown through changes in cell morphology and transcriptomic profiles. Last, using these hydrogel-cultured CAFs, microtubule dynamics are identified, but not actomyosin contractility, as a key mediator of CAF plasticity. The recapitulation of CAF heterogeneity in vitro using defined hydrogels presents unique opportunities for advancing the understanding of CAF biology and evaluation of CAF-targeting therapeutics.

5.
Phytomedicine ; 127: 155494, 2024 May.
Article En | MEDLINE | ID: mdl-38471370

BACKGROUND: Parkinson's disease (PD), a neurodegenerative disorder, is characterized by motor symptoms due to the progressive loss of dopaminergic neurons in the substantia nigra (SN) and striatum (STR), alongside neuroinflammation. Asiaticoside (AS), a primary active component with anti-inflammatory and neuroprotective properties, is derived from Centella asiatica. However, the precise mechanisms through which AS influences PD associated with inflammation are not yet fully understood. PURPOSE: This study aimed to explore the protective mechanism of AS in PD. METHODS: Targets associated with AS and PD were identified from the Swiss Target Prediction, Similarity Ensemble Approach, PharmMapper, and GeneCards database. A protein-protein interaction (PPI) network was constructed to identify potential therapeutic targets. Concurrently, GO and KEGG analyses were performed to predict potential signaling pathways. To validate these mechanisms, the effects of AS on 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD in mice were investigated. Furthermore, neuroinflammation and the activation of the NLRP3 inflammasome were assessed to confirm the anti-inflammatory properties of AS. In vitro experiments in BV2 cells were then performed to investigate the mechanisms of AS in PD. Moreover, CETSA, molecular docking, and molecular dynamics simulations (MDs) were performed for further validation. RESULTS: Network pharmacology analysis identified 17 potential targets affected by AS in PD. GO and KEGG analyses suggested the biological roles of these targets, demonstrating that AS interacts with 149 pathways in PD. Notably, the NOD-like receptor signaling pathway was identified as a key pathway mediating AS's effect on PD. In vivo studies demonstrated that AS alleviated motor dysfunction and reduced the loss of dopaminergic neurons in MPTP-induced PD mice. In vitro experiments demonstrated that AS substantially decreased IL-1ß release in BV2 cells, attributing this to the modulation of the NLRP3 signaling pathway. CETSA and molecular docking studies indicated that AS forms a stable complex with NLRP3. MDs suggested that ARG578 played an important role in the formation of the complex. CONCLUSION: In this study, we first predicted that the potential target and pathway of AS's effect on PD could be NLRP3 protein and NOD-like receptor signaling pathway by network pharmacology analysis. Further, we demonstrated that AS could alleviate symptoms of PD induced by MPTP through its interaction with the NLRP3 protein for the first time by in vivo and in vitro experiments. By binding to NLRP3, AS effectively inhibits the assembly and activation of the inflammasome. These findings suggest that AS is a promising inhibitor for PD driven by NLRP3 overactivation.


MPTP Poisoning , Neuroprotective Agents , Parkinson Disease , Triterpenes , Mice , Animals , Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , MPTP Poisoning/drug therapy , MPTP Poisoning/metabolism , Neuroprotection , Neuroinflammatory Diseases , Molecular Docking Simulation , Microglia , Parkinson Disease/metabolism , Dopaminergic Neurons , Anti-Inflammatory Agents/therapeutic use , Mice, Inbred C57BL , Disease Models, Animal , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/metabolism , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use
6.
Front Immunol ; 15: 1295309, 2024.
Article En | MEDLINE | ID: mdl-38426098

Background: Chronic rhinosinusitis (CRS) is a chronic inflammatory disease with an autoimmune background. Altered expression levels of T cell immunoglobulin and mucin-domain containing-3 (TIM-3), C-X-C chemokine receptor type 5 (CXCR5), and programmed cell death protein 1 (PD-1) are implicated in the progression of inflammatory and autoimmune diseases. Moreover, CXCR5+TIM-3-PD-1+ stem-like cytotoxic T cells function as memory stem cells during chronic disease processes and retain cytotoxicity-related gene networks. Objectives: To explore the expressions of CXCR5, TIM-3, and PD-1 on T cells and their correlation with clinical parameters in CRS. Methods: Flow cytometry was used to assess the expressions and co-expressions of CXCR5, TIM-3, and PD-1 on T cells in the tissues of the paranasal sinus and peripheral blood of patients with CRS as well as healthy controls. Immunofluorescence was used to assess the co-localization of TIM-3, CXCR5, and PD-1 with T cells. The disease severity of our patients with CRS was evaluated using the Lund-Mackay score. A complete blood count was also performed for the patients with CRS. Results: Expression levels of CXCR5 and PD-1 on T cells were significantly increased in the nasal tissues of patients with CRS. Compared with those in healthy controls, patients with CRS had high percentages of CXCR5+TIM-3-PD-1+ CD8+ and CD4+ T cells in nasal tissues, while no significant difference was observed in peripheral blood levels. Patients with CRS had a higher density of nasal CXCR5+TIM-3-PD-1+ T cells than that in healthy controls. CXCR5+TIM-3-PD-1+ CD8+ T cell levels in the nasal polyps of patients with CRS were negatively correlated with the patients' Lund-Mackay scores. The levels of CXCR5+TIM-3-PD-1+ T cells in nasal tissues were also negatively associated with disease duration and positively associated with the chronic inflammatory state of CRS. Conclusions: The level of CXCR5+TIM-3-PD-1+ stem cell-like T cells, especially CXCR5+TIM-3-PD-1+ CD8+ T cells, is increased in CRS. Therefore, inducing CXCR5+TIM-3-PD-1+ T cell exhaustion may be an effective immunotherapy for CRS.


Rhinosinusitis , Sinusitis , Humans , CD8-Positive T-Lymphocytes , T-Lymphocytes, Cytotoxic/metabolism , Hepatitis A Virus Cellular Receptor 2/metabolism , Programmed Cell Death 1 Receptor/metabolism , Chronic Disease , Patient Acuity , Receptors, CXCR5/metabolism
8.
Animals (Basel) ; 14(3)2024 Jan 28.
Article En | MEDLINE | ID: mdl-38338070

In commercial dairy farms, mastitis is associated with increased antimicrobial use and associated resistance, which may affect milk production. This study aimed to develop sensor-based prediction models for naturally occurring clinical bovine mastitis using nine machine learning algorithms with data from 447 mastitic and 2146 healthy cows obtained from five commercial farms in Northeast China. The variables were related to daily activity, rumination time, and daily milk yield of cows, as well as milk electrical conductivity. Both Z-standardized and non-standardized datasets pertaining to four specific stages of lactation were used to train and test prediction models. For all four subgroups, the Z-standardized dataset yielded better results than those of the non-standardized one, with the multilayer artificial neural net algorithm showing the best performance. Variables of importance had a similar rank in this algorithm, indicating the consistency of these variables as predictors for bovine mastitis in commercial farms with similar automatic systems. Moreover, the peak milk yield (PMY) of mastitic cows was significantly higher than that of healthy cows (p < 0.005), indicating that high-yielding cattle are more prone to mastitis. Our results show that machine learning algorithms are effective tools for predicting mastitis in dairy cows for immediate intervention and management in commercial farms.

9.
Nat Prod Res ; : 1-8, 2024 Feb 22.
Article En | MEDLINE | ID: mdl-38389428

Quality markers (Q-markers) are of great significance for quality evaluation of herbal medicines. Zhenyuan Capsule (ZYC) is a kind of Chinese patent medicine used to treat cardiovascular diseases. However, reliable and effective Q-markers for ZYC are still lacking. Herein, a UHPLC-Q/Orbitrap-MS/MS was performed to characterise the preliminary chemical profile of ZYC. A total of 86 components were characterised among which 20 constituents were unambiguously identified by reference compounds. Based on network pharmacology, seven major ginsenosides with great importance in the network were identified as Q-markers among which ginsenoside Re with the highest betweenness was screened to inhibit the development of coronary heart disease (CHD) by binding with vascular endothelial growth factor A (VEGFA). Docking and molecular dynamics simulation studies suggested that ginsenoside Re stably bound to VEGFA. Quantitative determination and chemical fingerprinting analysis were performed using HPLC-DAD. The results showed that ginsenosides screened might function as potential Q-markers for ZYC.

10.
Front Public Health ; 12: 1284180, 2024.
Article En | MEDLINE | ID: mdl-38356943

Objectives: The proportion of middle-aged and older adult people exposed to the Internet continues to grow. Internet use may have an impact on the mental health of the older adult, especially loneliness. This study analyzed the relationship between Internet use and presence of loneliness. Methods: A total of 550 person aged 45 years and above were randomly selected from a province in eastern China at the end of 2022. The outcome variable was presence of loneliness, as measured by self-report. Descriptive analysis, chi-square test and binary logistic analysis were used to analyze the data. Results: 58.3% of respondents use the Internet. Internet use could reduce the possible of reported loneliness in middle-aged and older adult people (OR = 0.652, 95%CI: 0.465, 0.940), and residence played a moderating role in the relationship between them. Middle-aged and older adults who used the Internet for 1-3 h (OR = 0.464, 95%CI: 0.275, 0.784) and 3-5 h (OR = 0.484, 95%CI: 0.247, 0.946) were less likely to felt lonely than those who used the Internet for less than 1 h per day. In addition, middle-aged and older adult people using the Internet to contact relatives and friends (OR = 0.488, 95%CI:0.292, 0.818), read the news (OR = 0.485, 95%CI:0.277, 0.848), assets management (OR = 0.297, 95%CI:0.109, 0.818) were less likely to report loneliness, while those who made online payment (OR = 3.101, 95%CI:1.413, 6.807) were more likely to report loneliness. Conclusion: There is a significant negative correlation between Internet use and presence of loneliness, but different Internet duration and content have different effects on loneliness in middle-aged and older adult people. We should pay attention to the impact of Internet use on loneliness in middle-aged and older adult people.


Internet Use , Loneliness , Middle Aged , Humans , Aged , Loneliness/psychology , Emotions , Internet , China
11.
PeerJ Comput Sci ; 10: e1761, 2024.
Article En | MEDLINE | ID: mdl-38196948

For the analysis of art works, accurate identification of various elements of works through deep learning methods is helpful for artists to appreciate and learn works. In this study, we leverage deep learning methodologies to precisely identify the diverse elements within graphic art designs, aiding artists in their appreciation and learning process. Our approach involves integrating the attention mechanism into an enhanced Single Shot MultiBox Detector (SSD) model to refine the recognition of artistic design elements. Additionally, we improve the feature fusion structure of the SSD model by incorporating long-range attention mechanism information, thus enhancing target detection accuracy. Moreover, we refine the Feature Pyramid Transformer (FPT) attention mechanism model to ensure the output feature map aligns effectively with the requirements of object detection. Our empirical findings demonstrate that our refined approach outperforms the original SSD algorithm across all four evaluation metrics, exhibiting improvements of 1.52%, 1.89%, 3.09%, and 2.57%, respectively. Qualitative tests further illustrate the accuracy, robustness, and universality of our proposed method, particularly in scenarios characterized by dense artistic elements and challenging-to-distinguish categories within art compositions.

12.
BMC Cancer ; 24(1): 73, 2024 Jan 13.
Article En | MEDLINE | ID: mdl-38218803

INTRODUCTION: Several studies have proved that Polygenic Risk Score (PRS) is a potential candidate for realizing precision screening. The effectiveness of low-dose computed tomography (LDCT) screening for lung cancer has been proved to reduce lung cancer specific and overall mortality, but the cost-effectiveness of diverse screening strategies remained unclear. METHODS: The comparative cost-effectiveness analysis used a Markov state-transition model to assess the potential effect and costs of the screening strategies incorporating PRS or not. A hypothetical cohort of 300,000 heavy smokers entered the study at age 50-74 years and were followed up until death or age 79 years. The model was run with a cycle length of 1 year. All the transition probabilities were validated and the performance value of PRS was extracted from published literature. A societal perspective was adopted and cost parameters were derived from databases of local medical insurance bureau. Sensitivity analyses and scenario analyses were conducted. RESULTS: The strategy incorporating PRS was estimated to obtain an ICER of CNY 156,691.93 to CNY 221,741.84 per QALY gained compared with non-screening with the initial start age range across 50-74 years. The strategy that screened using LDCT alone from 70-74 years annually could obtain an ICER of CNY 80,880.85 per QALY gained, which was the most cost-effective strategy. The introduction of PRS as an extra eligible criteria was associated with making strategies cost-saving but also lose the capability of gaining more LYs compared with LDCT screening alone. CONCLUSION: The PRS-based conjunctive screening strategy for lung cancer screening in China was not cost-effective using the willingness-to-pay threshold of 1 time Gross Domestic Product (GDP) per capita, and the optimal screening strategy for lung cancer still remains to be LDCT screening for now. Further optimization of the screening modality can be useful to consider adoption of PRS and prospective evaluation remains a research priority.


Lung Neoplasms , Humans , Middle Aged , Aged , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/genetics , Cost-Effectiveness Analysis , Early Detection of Cancer/methods , Genetic Risk Score , Cost-Benefit Analysis , Tomography, X-Ray Computed/methods , Quality-Adjusted Life Years , Mass Screening
13.
Sci Adv ; 10(5): eadg7887, 2024 Feb 02.
Article En | MEDLINE | ID: mdl-38295166

Protein tyrosine phosphatases (PTPs) play major roles in cancer and are emerging as therapeutic targets. Recent reports suggest low-molecular weight PTP (LMPTP)-encoded by the ACP1 gene-is overexpressed in prostate tumors. We found ACP1 up-regulated in human prostate tumors and ACP1 expression inversely correlated with overall survival. Using CRISPR-Cas9-generated LMPTP knockout C4-2B and MyC-CaP cells, we identified LMPTP as a critical promoter of prostate cancer (PCa) growth and bone metastasis. Through metabolomics, we found that LMPTP promotes PCa cell glutathione synthesis by dephosphorylating glutathione synthetase on inhibitory Tyr270. PCa cells lacking LMPTP showed reduced glutathione, enhanced activation of eukaryotic initiation factor 2-mediated stress response, and enhanced reactive oxygen species after exposure to taxane drugs. LMPTP inhibition slowed primary and bone metastatic prostate tumor growth in mice. These findings reveal a role for LMPTP as a critical promoter of PCa growth and metastasis and validate LMPTP inhibition as a therapeutic strategy for treating PCa through sensitization to oxidative stress.


Prostatic Neoplasms , Male , Humans , Mice , Animals , Molecular Weight , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/genetics , Tyrosine , Protein Tyrosine Phosphatases/metabolism
14.
Expert Rev Pharmacoecon Outcomes Res ; 24(1): 155-160, 2024 Jan.
Article En | MEDLINE | ID: mdl-37754783

BACKGROUND: Empirical support for the appropriate cost-effectiveness threshold (CET) in China remains sparse. OBJECTIVE: This study aimed to estimate the willingness to pay (WTP) for cancer prevention and treatment from the perspective of healthcare policy-makers (i.e. supply side) and to investigate whether there is a difference between the estimated WTP in two scenarios. METHODS: We conducted a web-based survey from May to July 2022 among experts who offering consultation to the government. We surveyed 79 experts from a national think-tank (84.81% response rate) using contingent valuation method, a method for estimating the monetary value that individuals place on a non-market service. RESULTS: The mean WTP for two scenarios were estimated at 1.29 times of per capita Gross Domestic Product (GDP) of China and 1.90 times of per capita GDP, respectively. There was a difference between the WTP in the two scenarios and the WTP for treatment was significantly higher than prevention. CONCLUSION: The findings suggest that though there is a smaller gap between the two scenarios in China as compared to other countries, the WTP may vary under different scenarios. So there's a need to further refine the development of CET by adding parameters like prevention instead of defining one universal threshold.


Neoplasms , Humans , Cost-Benefit Analysis , Neoplasms/prevention & control , Delivery of Health Care , China , Surveys and Questionnaires
15.
Bioresour Technol ; 393: 130156, 2024 Feb.
Article En | MEDLINE | ID: mdl-38056679

The efficient control of nitrogen loss in composting and the enhancement of product quality have become prominent concerns in current research. The positive role of varying concentrations kaolin in reducing nitrogen loss during composting was revealed using metagenomic binning combined with reverse transcription quantitative polymerase chain reaction. The results indicated that the addition of 0.5 % kaolin significantly (P < 0.05) up-regulated the expression of nosZ and nifH on day 35, while concurrently reducing norB abundance, resulting in a reduction of NH3 and N2O emissions by 61.4 % and 17.5 %, respectively. Notably, this study represents the first investigation into the co-occurrence of nitrogen functional genes and heavy metal resistance genes within metagenomic assembly genomes during composting. Emerging evidence indicates that kaolin effectively impedes the binding of Cu/Zn to nirK and nosZ gene reductases through passivation. This study offers a novel approach to enhance compost quality and waste material utilization.


Composting , Kaolin , Swine , Animals , Manure , Soil , Nitrogen Cycle , Nitrogen
16.
ISA Trans ; 144: 211-219, 2024 Jan.
Article En | MEDLINE | ID: mdl-37977886

This paper concerns the tracking control problem of a class of uncertain nonlinear systems subject to deferred time-varying state constraints and external disturbances. The states of the system are free in the initial phase and are restricted by some time-varying constraints after a particular time. A class of novel shifting functions are defined, which make any initial states that beyond the constraint region move to the desired position (such as zero). Thereafter, a new state transformation is implemented for the shifted state, which transforms the state constraint problem into the boundedness of a new variable. Compared with the existing BLF method, this approach avoids feasibility test for virtual control variables. Adaptive backstepping control and dynamic surface control are used in system controller design and stability analysis, and the ideal tracking performance is achieved. Finally, simulation example and comparative studies are carried out to illustrate the effectiveness and outstanding characteristics of the proposed approach. Simulation results show that the proposed control scheme broadens the scope of application, shortens running time and improves control efficiency compared with the existing control strategies.

17.
Int J Nanomedicine ; 18: 7825-7845, 2023.
Article En | MEDLINE | ID: mdl-38144511

Recent successive approval of anti-amyloid-ß (Aß) monoclonal antibodies as disease-modifying therapies against Alzheimer's disease (AD) has raised great confidence in the development of anti-AD therapies; however, the current therapies still face the dilemma of significant adverse reactions and limited effects. In this review, we summarized the therapeutic characteristics of the approved anti-Aß immunotherapies and dialectically analyzed the gains and losses from clinical trials. The review further proposed the reasonable selection of animal models in preclinical studies from the perspective of different animal models of Aß deposition and deals in-depth with the recent advances of exploring preclinical nanomedical application in Aß targeted therapy, aiming to provide a reliable systematic summary for the development of novel anti-Aß therapies. Collectively, this review comprehensively dissects the pioneering work of Aß-targeted therapies and proposed perspective insight into AD-modified therapies.


Alzheimer Disease , Animals , Alzheimer Disease/drug therapy , Amyloid beta-Peptides , Immunotherapy , Models, Animal , Nanomedicine , Humans
18.
J Agric Food Chem ; 71(46): 18046-18058, 2023 Nov 22.
Article En | MEDLINE | ID: mdl-37957030

Fruit size is crucial for fruit trees, as it contributes to both quality and yield. However, the underlying mechanism of fruit size regulation remains largely unknown. Taking advantage of using a fruit double-sized bud mutant of Chinese jujube, "Jinkuiwang" and its wild type, "Jinsixiaozao", we carried out a comprehensive study on the mechanism of fruit size development in jujube. Using weighted gene coexpression network analyses, a number of candidate regulators for fruit size including those involved in hormonal signaling pathways, transcription factors, and heat shock proteins were identified. A hub gene named cytokinin oxidase/dehydrogenase 5 (ZjCKX5), responsible for cytokinin degradation, was found to play a negative role in regulating fruit size development, and overexpressing ZjCKX5 in tomato and Arabidopsis resulted in much smaller fruits and dwarf plants. Furthermore, another two hub genes, ZjWRKY23 and ZjWRKY40 transcription factors, were found to participate in fruit size regulation by targeting and downregulating the ZjCKX5 expression. Overexpressing ZjWRKY23 or ZjWRKY40 in tomato led to much larger fruits and promoted plant architecture. Based on these results, a molecular framework for jujube fruit size regulation, namely, ZjWRKY-ZjCKX5 module, was proposed. This study provides a new insight into the molecular networks underlying fruit size regulation.


Fruit , Oxidoreductases , Transcription Factors , Ziziphus , Fruit/growth & development , Gene Expression Regulation, Plant , Oxidoreductases/genetics , Oxidoreductases/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Ziziphus/genetics
19.
Front Neurosci ; 17: 1228645, 2023.
Article En | MEDLINE | ID: mdl-37965216

Objective: The study aimed to investigate the comprehensive characteristics of brain functional activity and integration in patients with subcortical stroke using dynamic and static analysis methods and to examine whether alterations in brain functional activity and integration were associated with clinical symptoms of patients. Methods: Dynamic amplitude of low-frequency fluctuation (dALFF), static amplitude of low-frequency fluctuation (sALFF), dynamic degree centrality (dDC), and static degree centrality (sDC) were calculated for 19 patients with right subcortical stroke, 16 patients with left subcortical stroke, and 25 healthy controls (HC). Furthermore, correlation analysis was performed to investigate the relationships between changes in brain functional measurements of patients and clinical variables. Results: Group comparison results showed that significantly decreased dALFF in the left angular (ANG_L) and right inferior parietal gyrus (IPG_R), decreased sALFF in the left precuneus (PCUN_L), and decreased sDC in the left crus II of cerebellar hemisphere (CERCRU2_L) and IPG_R, while significantly increased sDC in the right lobule X of cerebellar hemisphere (CER10_R) were detected in patients with right subcortical stroke relative to HC. Patients with left subcortical stroke showed significantly decreased sALFF in the left precuneus (PCUN_L) but increased sDC in the right hippocampus (HIP_R) compared with HC. Additionally, the altered sDC values in the CER10_R of patients with right subcortical stroke and in the HIP_R of patients with left subcortical stroke were associated with the severity of stroke and lower extremities motor function. A correlation was also found between the altered sALFF values in the PCUN_L of patients with left subcortical stroke and lower extremities motor function. Conclusion: These findings suggest that time-varying brain activity analysis may supply complementary information for static brain activity analysis. Dynamic and static brain functional activity and integration analysis may contribute to a more comprehensive understanding of the underlying neuropathology of dysfunction in stroke patients.

20.
Pharm Dev Technol ; 28(9): 856-864, 2023 Nov.
Article En | MEDLINE | ID: mdl-37842809

Docetaxel (DTX) is an artificial semi-synthetic second-generation taxane anti-tumor drug, which is suitable for the treatment of various cancers such as lung cancer. The route of administration of DTX formulations has been extended to oral, intravenous, and rectal, with few studies on pulmonary administration being reported. Here, we had developed DTX liposomes (DTX-lips) for pulmonary inhalation administration. The particle size of the preparation was 125 nm, the encapsulation efficiency was 94.4 ± 0.14%, and the drug loading capacity was 1.26 ± 0.01%. It had good stability. The fine particle fraction with aerodynamic diameter less than 6.4 µm accounts for 64.63 ± 0.12%, showed excellent aerosolization performance. DTX-lips were slow to release in simulated lung fluid. The fluorescence distribution experimented in mice and tissues showed that the fluorescence of the inhaled liposome group was mainly distributed in the lung, and the retention time was significantly prolonged as compared with those of the other two groups. No significant fluorescence was observed in other tissues, which was conducive to the full effect of the drug in the lung tissue. DTX-lips had no damage to respiratory system and whole body. These results indicated that the inhaled DTX-lips had good lung targeting, reduced accumulation in other organs, and improved the safety and effectiveness of the drug.


Antineoplastic Agents , Lung Neoplasms , Mice , Animals , Docetaxel , Liposomes , Lung , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Cell Line, Tumor , Drug Carriers
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