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1.
Osteoporos Int ; 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39120624

ABSTRACT

Identifying dysregulated plasma proteins in osteoporosis (OP) progression offers insights into prevention and treatment. This study found 8 such proteins associated with OP, suggesting them as therapy targets. This discovery may cut drug development costs and improve personalized treatments. PURPOSE: This study aims to identify potential therapeutic targets for OP using summary data-based Mendelian randomization (SMR) and colocalization analysis methods. Furthermore, we seek to explore the biological significance and pharmacological value of these drug targets. METHODS: To identify potential therapeutic targets for OP, we conducted SMR and colocalization analysis. Plasma protein (pQTL, exposure) data were sourced from the study by Ferkingstad et al. (n = 35,559). Summary statistics for bone mineral density (BMD, outcome) were obtained from the GWAS Catalog (n = 56,284). Additionally, we utilized enrichment analysis, protein-protein interaction (PPI) network analysis, drug prediction, and molecular docking to further analyze the biological significance and pharmacological value of these drug targets. RESULTS: In the SMR analysis, while 20 proteins showed significance, only 8 potential drug targets (GCKR, ERBB3, CFHR1, GPN1, SDF2, VTN, BET1L, and SERPING1) received support from colocalization (PP.H4 > 0.8). These proteins are closely associated with immune function in terms of biological significance. Molecular docking also demonstrated favorable binding of drugs to proteins, consistent with existing structural data, further substantiating the pharmacological value of these targets. CONCLUSIONS: The study identified 8 potential drug targets for OP. These prospective targets are believed to have a higher chance of success in clinical trials, thus aiding in prioritizing OP drug development and reducing development costs.

2.
J Org Chem ; 89(8): 5328-5336, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38595055

ABSTRACT

The thiazole-2-imine derivatives with interesting pharmacological activities have attracted significant attention. However, previously reported synthesis strategies usually suffered from some drawbacks, such as the use of metals/additive and harsh reaction conditions. Herein, we developed a metal- and photoinitiator-free photocatalytic strategy for the synthesis of various selenium-substituted thiazole-2-imine derivatives for the first time. The reaction displayed mild reaction conditions, simple operation, a broad substrate scope (37 examples), and good to excellent yields.

3.
Org Biomol Chem ; 22(16): 3198-3203, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38563151

ABSTRACT

Novel construction methods for obtaining 3,4'-pyran spirooxindole heterocyclic skeletons have always been the focus of attention. Herein, we report a highly enantioselective inverse-electron-demand oxa-Diels-Alder cycloaddition reaction of a ß,γ-unsaturated pyrazole amide and a N-diphenyl isatin-derived oxodiene using a bifunctional catalyst. In addition, large-scale experiments confirmed the reliability of the reaction. The resultant products of this study can be further transformed.

4.
BMC Public Health ; 24(1): 2109, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39103831

ABSTRACT

BACKGROUND: Loneliness and social isolation have been found to be associated with various health-related outcomes. Our study aimed to evaluate the association of loneliness and social isolation with the risk of glaucoma. METHODS: A total of 373,330 participants from the UK Biobank without glaucoma at recruitment were included in this study. Self-reported questionnaires were used to define loneliness and social isolation. Incident glaucoma events were identified by hospital inpatient admissions and self-reported data. COX proportional hazards models adjusted for sociodemographic, lifestyle, and health-related factors were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: During a median follow-up of 13.1 (interquartile range: 12.3-13.9) years, 6,489 participants developed glaucoma. After adjusting for confounding factors, loneliness (yes vs. no: adjusted HR: 1.16; 95% CI: 1.04-1.30; P = 0.009) and social isolation (yes vs. no: adjusted HR: 1.08; 95% CI: 1.01-1.16; P = 0.033) were associated with an increased risk of glaucoma. CONCLUSIONS: In this population-based prospective cohort study, loneliness and social isolation were associated with a higher risk of glaucoma.


Subject(s)
Glaucoma , Loneliness , Social Isolation , Humans , Loneliness/psychology , United Kingdom/epidemiology , Social Isolation/psychology , Male , Female , Middle Aged , Glaucoma/psychology , Glaucoma/epidemiology , Prospective Studies , Risk Factors , Aged , Adult , Biological Specimen Banks , Proportional Hazards Models , Surveys and Questionnaires , Self Report , UK Biobank
5.
BMC Health Serv Res ; 24(1): 23, 2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38178099

ABSTRACT

OBJECTIVE: The outbreak of the COVID-19 pandemic has drawn attention from all sectors of society to the level of public health services. This study aims to investigate the level of public health service supply in the four major regions of Guangdong Province, providing a basis for optimizing health resource allocation. METHODS: This article uses the entropy method and panel data of 21 prefecture-level cities in Guangdong Province from 2005 to 2021 to construct the evaluation index system of public health service supply and calculate its supply index. On this basis, the standard deviation ellipse method, kernel density estimation, and Markov chain are used to analyze the spatiotemporal evolution trend of the public health service supply level in Guangdong Province. The Dagum Gini coefficient and panel regression model are further used to analyze the relative differences and the key influencing factors of difference formation. Finally, the threshold effect model is used to explore the action mechanism of the key factors. RESULTS: Overall, the level of public health service supply in Guangdong Province is on an upward trend. Among them, polarization and gradient effects are observed in the Pearl River Delta and Eastern Guangdong regions; the balance of public health service supply in Western Guangdong and Northern Mountainous areas has improved. During the observation period, the level of public health services in Guangdong Province shifted towards a higher level with a smaller probability of leapfrogging transition, and regions with a high level of supply demonstrated a positive spillover effect. The overall difference, intra-regional difference and inter-regional difference in the level of public health service supply in Guangdong Province during the observation period showed different evolutionary trends, and spatial differences still exist. These differences are more significantly positively affected by factors such as the level of regional economic development, the degree of fiscal decentralization, and the urbanization rate. Under different economic development threshold values, the degree of fiscal decentralization and urbanization rate both have a double threshold effect on the role of public health service supply level. CONCLUSION: The overall level of public health service supply in Guangdong Province has improved, but spatial differences still exist. Key factors influencing these differences include the level of regional economic development, the degree of fiscal decentralization, and the urbanization rate, all of which exhibit threshold effects. It is suggested that, in view of the actual situation of each region, efforts should be made to build and maintain their own advantages, enhance the spatial linkage of public health service supply, and consider the threshold effects of key factors in order to optimize the allocation of health resources.


Subject(s)
Pandemics , Urbanization , Humans , China/epidemiology , Cities , Health Services
6.
Article in English | MEDLINE | ID: mdl-39120969

ABSTRACT

BACKGROUNDS: Urban-rural disparities in medical care, including in home healthcare, persist globally. With aging populations and medical advancements, demand for home health services rises, warranting investigation into home healthcare disparities. Our study aimed to 1) investigate the relationship between rurality on home healthcare quality, and 2) assess the temporal disparities and the changes in disparities in home healthcare quality between urban and rural home health agencies (HHAs), incorporating an analysis of geospatial distribution to visualize the underlying patterns. METHODS: This study analyzed data from HHAs listed on the Centers for Medicare and Medicaid Services (CMS) website, covering the period from 2010 to 2022. Data were classified into urban and rural categories for each HHA. We employed panel data analysis to examine the impact of rurality on home healthcare quality, specifically focusing on hospital admission and emergency room (ER) visit rates. Disparities between urban and rural HHAs were assessed using the Wilcoxon test, with results visualized through line and dot plots and heat maps to illustrate trends and differences comprehensively. RESULTS: The rurality is demonstrated as the most significant variable in hospital admission and ER visit rates in the panel data analysis. Urban HHAs consistently exhibit significantly lower hospital admission rates and ER visit rates compared to rural HHAs from 2010 to 2022. Longitudinally, the gap in hospital admission rates between urban and rural HHAs is shrinking, while there is an increasing gap in ER visit rates. In 2022, HHAs in Mountain areas which are characterized by a higher proportion of rural regions exhibited higher hospital admission and ER visit rates than other areas. CONCLUSIONS: This study underscores the persistent urban-rural disparities in home healthcare quality. The analysis emphasizes the ongoing need for targeted interventions to address disparities in home healthcare delivery and ensure equitable access to quality care across urban and rural regions. Our findings have the potential to inform policy and practice, promoting equity and efficiency in the long-term care system, for better health outcomes throughout the United States.

7.
J Adv Nurs ; 2024 Jul 13.
Article in English | MEDLINE | ID: mdl-39001661

ABSTRACT

AIM: To explore the mechanism of proactive personality influence on nurses' sense of social responsibility through a serial multiple mediation model of volunteering motivation and self-efficacy. DESIGN: Further analysis of a cross-sectional and survey-based study. METHODS: In June 2023, a study was conducted with 722 Chinese nurses from four hospitals. Data were collected using the Proactive Personality Scale, the Self-Efficacy Scale, the Motivation to Volunteer Scale and the Nurses' Sense of Social Responsibility Scale. Structural equation modelling was used to analyse the relationship between nurses' sense of social responsibility and its correlative factors. RESULTS: Structural equation modelling showed a good model fit. Proactive personality, self-efficacy and motivation to volunteer can directly influence nurses' sense of social responsibility (ß = .12, ß = .04, ß = .50, p < .05). According to the test of chained mediation effects, proactive personality was significant through a single mediation path of self-efficacy (Z = 2.33, p < .05) and motivation to volunteer (Z = 7.32, p < .05) and through successive mediation paths of both variables (Z = 3.33, p < .05). CONCLUSION: A proactive personality can motivate nurses' social responsibility. Therefore, prompting nurses to be more proactive can effectively enhance nurses' sense of social responsibility. REPORTING METHOD: This study was reported following the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for cross-sectional studies. PATIENT OR PUBLIC CONTRIBUTION: This study explored the mechanisms influencing nurses' sense of social responsibility at the end of the epidemic. The results may inform the maintenance of high levels of long-term effects of nurses' social responsibility and shed light on building a standing workforce for public health emergencies.

8.
Home Health Care Serv Q ; 43(3): 205-219, 2024.
Article in English | MEDLINE | ID: mdl-38230702

ABSTRACT

This study identified the process and agency characteristics associated with poor utilization outcomes - higher percentages of patients (i) admitted to an acute care organization and (ii) visited an emergency room (ER) unplanned without hospitalization - for home health agencies (HHAs) in the United States. We conducted a secondary analysis of data about HHAs' various characteristics, process adherence levels, and utilization outcomes collected from disparate public repositories for 2010-2022. We developed descriptive tree-based models using HHAs' hospital admission or ER visit percentages as response variables. Across the board, hospital admission percentages have steadily improved while ER percentages deteriorated for an extended period. Recently, checking for fall risks and depression was associated with improved outcomes for urban agencies. In general, rural HHAs had worse utilization outcomes than urban HHAs. Targeted investments and improvement initiatives can help rural HHAs close the urban-rural gap in the future.


Subject(s)
Home Care Services , Humans , United States , Home Care Services/statistics & numerical data , Home Care Services/trends , Home Care Services/standards , Male , Female , Home Care Agencies/statistics & numerical data , Patient Acceptance of Health Care/statistics & numerical data , Patient Acceptance of Health Care/psychology , Emergency Service, Hospital/statistics & numerical data , Aged , Hospitalization/statistics & numerical data
9.
J Environ Manage ; 360: 121206, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38776658

ABSTRACT

The greenhouse gas (GHG) emissions from wastewater treatment plants (WWTPs), consisting mainly of methane (CH4) and nitrous oxide (N2O), have been constantly increasing and become a non-negligible contributor towards carbon neutrality. The precise evaluation of plant-specific GHG emissions, however, remains challenging. The current assessment approach is based on the product of influent load and emission factor (EF), of which the latter is quite often a single value with huge uncertainty. In particular, the latest default Tier 1 value of N2O EF, 0.016 ± 0.012 kgN2O-N kgTN-1, is estimated based on the measurement of 30 municipal WWTPs only, without involving any industrial wastewater. Therefore, to resolve the pattern of GHG emissions from industrial WWTPs, this work conducted a 14-month monitoring campaign covering all the process units at a full-scale industrial WWTP in Shanghai, China. The total CH4 and N2O emissions from the whole plant were, on average, 447.7 ± 224.5 kgCO2-eq d-1 and 1605.3 ± 2491.0 kgCO2-eq d-1, respectively, exhibiting a 5.2- or 3.9-times more significant deviation than the influent loads of chemical oxygen demand (COD) or total nitrogen (TN). The resulting EFs, 0.00072 kgCH4 kgCOD-1 and 0.00211 kgN2O-N kgTN-1, were just 0.36% of the IPCC recommended value for CH4, and 13.2% for N2O. Besides, the parallel anoxic-oxic (A/O) lines of this industrial WWTP were covered in two configurations, allowing the comparison of GHG emissions from different odor control setup. Unit-specific analysis showed that the replacement of enclosed A/open O with enclosed A/O reduced the CH4 EF by three times, from 0.00159 to 0.00051 kgCH4 kgCOD-1, and dramatically decreased the N2O EF by an order of magnitude, from 0.00376 to 0.00032 kgN2O-N kgTN-1, which was among the lowest of all full-scale WWTPs.


Subject(s)
Greenhouse Gases , Methane , Nitrous Oxide , Wastewater , Greenhouse Gases/analysis , Wastewater/chemistry , Wastewater/analysis , Nitrous Oxide/analysis , Methane/analysis , Environmental Monitoring , Waste Disposal, Fluid/methods , China
10.
Small ; 19(48): e2302704, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37605327

ABSTRACT

Patients with osteoporotic fractures often require effective fixation and subsequent bone repair. However, currently available materials are often limited functionally, failing to improve this cohort's outcomes. Herein, kaempferol-loaded mesoporous bioactive glass nanoparticles (MBGNs)-doped orthopedic adhesives are prepared to assist osteoporotic fracture fixation and restore dysregulated bone homeostasis, including promoting osteoblast formation while inhibiting osteoclastic bone-resorbing activity to synergistically promote osteoporotic fracture healing. The injectability, reversible adhesiveness and malleable properties endowed the orthopedic adhesives with high flexibility and hemostatic performance to adapt to complex clinical scenarios. Moreover, Ca2+ and SiO4 4- ions released from MBGNs can accelerate osteogenesis via the PI3K/AKT pathway, while kaempferol mediated osteoclastogenesis inhibition and can slow down the bone resorption process through NF-κB pathway, which regulated bone regeneration and remodeling. Importantly, implementing the orthopedic adhesive is validated as an effective closed-loop management approach in restoring the dysregulated bone homeostasis of osteoporotic fractures.


Subject(s)
Osteoporotic Fractures , Humans , Osteoporotic Fractures/therapy , Kaempferols/pharmacology , Adhesives , Phosphatidylinositol 3-Kinases , Osteogenesis , Homeostasis
11.
Planta ; 258(1): 14, 2023 Jun 13.
Article in English | MEDLINE | ID: mdl-37310483

ABSTRACT

MAIN CONCLUSION: Three Di19-4 genes were identified in mango. Overexpression of MiDi19-4B in A. thaliana promoted earlier flowering and enhanced drought, salt, and ABA resistance. Drought-induced protein 19 (Di19) is a drought-induced protein that is mainly involved in multiple stress responses. Here, three Di19-4 genes (MiDi19-4A/B/C) in mango (Mangifera indica L.) were identified, and the coding sequences (CDS) had lengths of 684, 666, and 672 bp and encoded proteins with 228, 222, and 224 amino acids, respectively. The promoters of the MiDi19-4 genes contained phytohormone-, light-, and abiotic stress-responsive elements. The MiDi19-4 genes were expressed in every tissue and highly expressed in leaves. Moreover, MiDi19-4 genes were highly correlated with the vegetative growth period and induced by polyethylene glycol (PEG) or salt stress. MiDi19-4B displayed the highest expression during the vegetative growth period and then showed decreased expression, and MiDi19-4B was highly expressed at both the late stage of the vegetative growth period and the initial stage of the flowering induction period. The 35S::GFP-MiDi19-4B fusion protein was located in the cell nucleus. The transgenic plants ectopically expressing MiDi19-4B exhibited earlier flowering and increased expression patterns of FRUITFULL (AtFUL), APETALA1 (AtAP1), and FLOWERING LOCUS T (AtFT). The drought and salt tolerance of MiDi19-4B transgenic plants was significantly increased, and these plants showed decreased sensitivity to abscisic acid (ABA) and considerably increased expression levels of drought- and salt-related genes and ABA signalling pathway genes. Additionally, bimolecular fluorescence complementation (BiFC) experiments revealed that the MiDi19-4B protein interacted with CAULIFLOWER (MiCAL1), MiCAL2, MiAP1-1, and MiAP1-2. Taken together, these results highlighted the important regulatory roles of MiDi19-4B in tolerance to multiple abiotic stresses and in flowering.


Subject(s)
Arabidopsis , Mangifera , Abscisic Acid/metabolism , Arabidopsis/genetics , Ectopic Gene Expression , Exons , Mangifera/genetics , Plants, Genetically Modified/genetics
12.
PLoS Comput Biol ; 18(6): e1010239, 2022 06.
Article in English | MEDLINE | ID: mdl-35759520

ABSTRACT

Key features of long-term memory (LTM), such as its stability and persistence, are acquired during processes collectively referred to as consolidation. The dynamics of biological changes during consolidation are complex. In adult rodents, consolidation exhibits distinct periods during which the engram is more or less resistant to disruption. Moreover, the ability to consolidate memories differs during developmental periods. Although the molecular mechanisms underlying consolidation are poorly understood, the initial stages rely on interacting signaling pathways that regulate gene expression, including brain-derived neurotrophic factor (BDNF) and Ca2+/calmodulin-dependent protein kinase II α (CaMKIIα) dependent feedback loops. We investigated the ways in which these pathways may contribute to developmental and dynamical features of consolidation. A computational model of molecular processes underlying consolidation following inhibitory avoidance (IA) training in rats was developed. Differential equations described the actions of CaMKIIα, multiple feedback loops regulating BDNF expression, and several transcription factors including methyl-CpG binding protein 2 (MeCP2), histone deacetylase 2 (HDAC2), and SIN3 transcription regulator family member A (Sin3a). This model provides novel explanations for the (apparent) rapid forgetting of infantile memory and the temporal progression of memory consolidation in adults. Simulations predict that dual effects of MeCP2 on the expression of bdnf, and interaction between MeCP2 and CaMKIIα, play critical roles in the rapid forgetting of infantile memory and the progress of memory resistance to disruptions. These insights suggest new potential targets of therapy for memory impairment.


Subject(s)
Brain-Derived Neurotrophic Factor , Memory Consolidation , Animals , Avoidance Learning/physiology , Brain-Derived Neurotrophic Factor/metabolism , Hippocampus/physiology , Humans , Memory, Long-Term/physiology , Methyl-CpG-Binding Protein 2/genetics , Methyl-CpG-Binding Protein 2/metabolism , Methyl-CpG-Binding Protein 2/pharmacology , Rats
13.
BMC Public Health ; 23(1): 959, 2023 05 26.
Article in English | MEDLINE | ID: mdl-37231366

ABSTRACT

BACKGROUND: The digital economy based on the internet and IT is developing rapidly in China, which makes a profound impact on urban environmental quality and residents' health activities. Thus, this study introduces environmental pollution as a mediating variable based on Grossman's health production function to explore the impact of digital economic development on the health of the population and its influence path. METHODS: Based on the panel data of 279 prefecture-level cities in China from 2011 to 2017, this paper investigates the acting mechanism of digital economic development on residents' health by employing a combination of mediating effects model and spatial Durbin model. RESULTS: The development of digital economy makes direct improvement on residents' health condition, which is also obtained indirectly by means of environmental pollution mitigation. Besides, from the perspective of spatial spillover effect, the development of digital economy also has a significant promoting effect on the health of adjacent urban residents, and further analysis reveals that the promoting effect in the central and western regions of China is more pronounced than that in the eastern region. CONCLUSIONS: Digital economy can have a direct promoting effect on the health of residents, and environmental pollution has an intermediary effect between digital economy and residents' health; At the same time, there is also a regional heterogeneity among the three relationships. Therefore, this paper believes that the government should continue to formulate and implement scientific digital economy development policies at the macro and micro levels to narrow the regional digital divide, improve environmental quality and enhance the health level of residents.


Subject(s)
Economic Development , Environmental Pollution , Humans , Cities , China/epidemiology , Government
14.
J Environ Manage ; 347: 119125, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-37816278

ABSTRACT

The gaseous elemental mercury (Hg0) emitted from coal-fired flue gas is extremely harmful to the atmospheric environment and human health. In this study, a 2D/2D Bi2MoO6(2 0 0)/g-C3N4 heterojunction photocatalyst was synthesized and exhibited a high visible-light driven Hg0 removal efficiency up to 99.5% in an atmosphere consisting of N2, O2 (6%), CO2 (12%), NO (100 ppm), SO2 (800 ppm), and H2O (5%). The introduction of surfactant CTAB led to further exposure of the highly active (2 0 0) crystal facet of Bi2MoO6, with a higher reactive oxygen species ratio than the original mainly exposed (1 3 1) crystal facet, and inhibited the agglomeration of Bi2MoO6, thereby greatly reducing the micro-thickness and improving the specific surface area. The smaller thickness effectively promoted the separation of photoinduced carriers and the speed of transfer to the interface. Additionally, through EPR characterization and work function calculation, we observed that the change in the exposed crystal facet regulated the Fermi level of Bi2MoO6 nanosheets, altering the direction of the built-in electric field at the interface with g-C3N4. This formation of an S-scheme 2D/2D Bi2MoO6(2 0 0)/g-C3N4 heterostructure further facilitated the recombination of unintentional carriers and strengthened the separation and catalysis of effective photogenerated carriers. To a certain extent, this work provides a guidance for the research of photocatalysis to achieve efficient and sustainable mercury removal from coal-fired flue gas.


Subject(s)
Mercury , Humans , Catalysis , Light , Coal
15.
J Environ Manage ; 343: 118182, 2023 Oct 01.
Article in English | MEDLINE | ID: mdl-37224687

ABSTRACT

Understanding how microbial processes develop and change in alpine meadow soils is key to global initiatives toward environmental sustainability and local land management. Yet, how microbial interactions mediate soil multifunctionality in disturbed and managed alpine meadows remains understudied. Here, we investigated multiple community metrics, particularly microbial network properties and assembly processes, of soil bacterial and fungal communities and their links to certain soil functions along a degradation-restoration sequence of alpine meadows in the Qinghai-Tibetan Plateau. Meadow degradation caused significant declines in soil hydraulic conductivity (e.g., higher bulk density, reduced soil porosity and water content) and nitrogen availability, leading to lowered soil multifunctionality. Meadow degradation only caused weak changes in microbial abundance, alpha diversity, and community composition, but remarkably reduced bacterial network complexity, to a less extent for fungal network properties. Short-term artificial restoration with productive grass monocultures did not restore soil multifunctionality, in turn even destabilized bacterial network and favored pathogenic over mutualistic fungi. Soil fungi community are more stable than bacteria in disturbed alpine meadows, and they evolved with distinct assembly strategies (stochastic-dominant versus deterministic-driven processes, respectively). Further, microbial network complexity, positively and better predicts soil multifunctionality than alpha diversity. Our work shows how microbial interaction complexity may enhance soil multifunctionality in degraded alpine meadow ecosystems, noting that meadow restoration with low plant species diversity may failed in restoring multiple ecosystem functions. These findings would help predict the outcomes of global environmental changes and inform management strategies in regional grassland conservation and restoration.


Subject(s)
Ecosystem , Grassland , Soil , Nitrogen/analysis , Plants , Soil Microbiology , Bacteria , Tibet
16.
Learn Mem ; 29(12): 435-446, 2022 12.
Article in English | MEDLINE | ID: mdl-36446603

ABSTRACT

Empirical and computational methods were combined to examine whether individual or dual-drug treatments can restore the deficit in long-term synaptic facilitation (LTF) of the Aplysia sensorimotor synapse observed in a cellular model of Coffin-Lowry syndrome (CLS). The model was produced by pharmacological inhibition of p90 ribosomal S6 kinase (RSK) activity. In this model, coapplication of an activator of the mitogen-activated protein kinase (MAPK) isoform ERK and an activator of protein kinase A (PKA) resulted in enhanced phosphorylation of RSK and enhanced LTF to a greater extent than either drug alone and also greater than their additive effects, which is termed synergism. The extent of synergism appeared to depend on another MAPK isoform, p38 MAPK. Inhibition of p38 MAPK facilitated serotonin (5-HT)-induced RSK phosphorylation, indicating that p38 MAPK inhibits activation of RSK. Inhibition of p38 MAPK combined with activation of PKA synergistically activated both ERK and RSK. Our results suggest that cellular models of disorders that affect synaptic plasticity and learning, such as CLS, may constitute a useful strategy to identify candidate drug combinations, and that combining computational models with empirical tests of model predictions can help explain synergism of drug combinations.


Subject(s)
Coffin-Lowry Syndrome , Cyclic AMP-Dependent Protein Kinases , Neuronal Plasticity , p38 Mitogen-Activated Protein Kinases , Humans , Coffin-Lowry Syndrome/physiopathology , Cyclic AMP-Dependent Protein Kinases/physiology , Mitogen-Activated Protein Kinases/physiology , Neuronal Plasticity/physiology , p38 Mitogen-Activated Protein Kinases/physiology , Serotonin/pharmacology
17.
Zhongguo Zhong Yao Za Zhi ; 48(17): 4798-4802, 2023 Sep.
Article in Zh | MEDLINE | ID: mdl-37802819

ABSTRACT

This article focused on the significant public health issue of comorbidities in the elderly population and highlighted the important role of traditional Chinese medicine(TCM) in the prevention and treatment of comorbidities in the elderly. It suggested that TCM should fully utilize its advantages in holistic perspective, syndrome differentiation and treatment, and preventive medicine in the process of preventing and treating comorbidities in the elderly. At the same time, in response to the significant shift in the disease spectrum of the elderly, the increasingly innovative concepts in diagnosis and treatment, the growing demand for proactive health by the el-derly population, and the current emphasis on patient-centered evaluation standards, it is necessary to further conduct basic theoretical and experimental research on comorbidities in the elderly using TCM, emphasize clinical research on comorbidities in the elderly, explore appropriate efficacy evaluation systems, improve TCM prevention and treatment strategies and comprehensive intervention programs for comorbidities in the elderly, and leverage the unique role of TCM in the rehabilitation of elderly comorbidity patients. By analyzing the potential of TCM in the field of comorbidities in the elderly, this article is expected to provide new insights for future clinical practice and scientific research.


Subject(s)
Drugs, Chinese Herbal , Medicine, Chinese Traditional , Aged , Humans , Public Health , Comorbidity , Drugs, Chinese Herbal/therapeutic use
18.
J Org Chem ; 87(21): 14685-14694, 2022 Nov 04.
Article in English | MEDLINE | ID: mdl-36205920

ABSTRACT

Ring opening of cycloalkanols has been employed as a commonly used strategy to prepare diverse distal functionalized ketones. However, most of these ketones obtained by this strategy belong to monofunctional ketones, while difunctional ketones with more potential application value have been rarely reported. Herein, we first reported a mild I2-promoted ring-opening selenation of cyclopropanol to synthesize various distal difunctional ketones. In the reaction, hydroxyl (-OH) derived from water and RSe+ from diselenide can be introduced into the α- and ß-positions, respectively, delivering ß-hydroxy selenylated ketones in good to excellent yields.

19.
BMC Public Health ; 22(1): 1208, 2022 06 17.
Article in English | MEDLINE | ID: mdl-35715790

ABSTRACT

BACKGROUND: With the accelerated global integration and the impact of climatic, ecological and social environmental changes, China will continue to face the challenge of the outbreak and spread of emerging infectious diseases and traditional ones. This study aims to explore the spatial and temporal evolutionary characteristics of the incidence of Class B notifiable infectious diseases in China from 2007 to 2020, and to forecast the trend of it as well. Hopefully, it will provide a reference for the formulation of infectious disease prevention and control strategies. METHODS: Data on the incidence rates of Class B notifiable infectious diseases in 31 provinces, municipalities and autonomous regions of China from 2007 to 2020 were collected for the prediction of the spatio-temporal evolution and spatial correlation as well as the incidence of Class B notifiable infectious diseases in China based on global spatial autocorrelation and Autoregressive Integrated Moving Average (ARIMA). RESULTS: From 2007 to 2020, the national incidence rate of Class B notifiable infectious diseases (from 272.37 per 100,000 in 2007 to 190.35 per 100,000 in 2020) decreases year by year, and the spatial distribution shows an "east-central-west" stepwise increase. From 2007 to 2020, the spatial clustering of the incidence of Class B notifiable infectious diseases is significant and increasing year by year (Moran's I index values range from 0.189 to 0.332, p < 0.05). The forecasted incidence rates of Class B notifiable infectious diseases nationwide from 2021 to 2024 (205.26/100,000, 199.95/100,000, 194.74/100,000 and 189.62/100,000) as well as the forecasted values for most regions show a downward trend, with only some regions (Guangdong, Hunan, Hainan, Tibet, Guangxi and Guizhou) showing an increasing trend year by year. CONCLUSIONS: The current study found that since there were significant regional disparities in the prevention and control of infectious diseases in China between 2007 and 2020, the reduction of the incidence of Class B notifiable infectious diseases requires the joint efforts of the surrounding provinces. Besides, special attention should be paid to provinces with an increasing trend in the incidence of Class B notifiable infectious diseases to prevent the re-emergence of certain traditional infectious diseases in a particular province or even the whole country, as well as the outbreak and spread of emerging infectious diseases.


Subject(s)
Communicable Diseases, Emerging , Communicable Diseases , China/epidemiology , Communicable Diseases/epidemiology , Humans , Incidence , Spatial Analysis , Spatio-Temporal Analysis
20.
Int J Mol Sci ; 23(18)2022 Sep 09.
Article in English | MEDLINE | ID: mdl-36142343

ABSTRACT

S-RNase plays vital roles in the process of self-incompatibility (SI) in Rutaceae plants. Data have shown that the rejection phenomenon during self-pollination is due to the degradation of pollen tube RNA by S-RNase. The cytoskeleton microfilaments of pollen tubes are destroyed, and other components cannot extend downwards from the stigma and, ultimately, cannot reach the ovary to complete fertilisation. In this study, four S-RNase gene sequences were identified from the 'XiangShui' lemon genome and ubiquitome. Sequence analysis revealed that the conserved RNase T2 domains within S-RNases in 'XiangShui' lemon are the same as those within other species. Expression pattern analysis revealed that S3-RNase and S4-RNase are specifically expressed in the pistils, and spatiotemporal expression analysis showed that the S3-RNase expression levels in the stigmas, styles and ovaries were significantly higher after self-pollination than after cross-pollination. Subcellular localisation analysis showed that the S1-RNase, S2-RNase, S3-RNase and S4-RNase were found to be expressed in the nucleus according to laser confocal microscopy. In addition, yeast two-hybrid (Y2H) assays showed that S3-RNase interacted with F-box, Bifunctional fucokinase/fucose pyrophosphorylase (FKGP), aspartic proteinase A1, RRP46, pectinesterase/pectinesterase inhibitor 51 (PME51), phospholipid:diacylglycerol acyltransferase 1 (PDAT1), gibberellin receptor GID1B, GDT1-like protein 4, putative invertase inhibitor, tRNA ligase, PAP15, PAE8, TIM14-2, PGIP1 and p24beta2. Moreover, S3-RNase interacted with TOPP4. Therefore, S3-RNase may play an important role in the SI of 'XiangShui' lemon.


Subject(s)
Aspartic Acid Proteases , Citrus , Self-Incompatibility in Flowering Plants , Citrus/metabolism , Diacylglycerol O-Acyltransferase , Endoribonucleases , Fucose , Gibberellins , Phospholipids , Plant Proteins/genetics , Plant Proteins/metabolism , Pollen/genetics , RNA , RNA Ligase (ATP) , Ribonucleases/genetics , Ribonucleases/metabolism , Self-Incompatibility in Flowering Plants/genetics , beta-Fructofuranosidase
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