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1.
Article in English | MEDLINE | ID: mdl-38958673

ABSTRACT

OBJECTIVE: This population-based study explored emergency room visits (ERVs) from all-causes, circulatory and respiratory diseases among different occupational groups in Taiwan associated with ambient average temperature. METHOD: Daily area-age-sex specific ERVs records were obtained from the Taiwan's Ministry of Health and Welfare from 2009 to 2018. Distributed lag-nonlinear model (DLNM) was used to estimate the exposure-response relationships between daily average temperature and ERVs for all-causes, circulatory and respiratory diseases by occupational groups. Random-effects meta-analysis was used to pool the overall cumulative relative risk (RR) and 95% confidence interval (CI). RESULTS: The exposure-response curves showed ERVs of all-cause and respiratory diseases increased with rising temperature across all occupational groups. These effects were consistently stronger among younger (20-64 years old) and outdoor workers. In contrast, ERVs risk from circulatory diseases increased significantly during cold snaps, with a substantially higher risk for female workers. Interestingly, female workers, regardless of indoor or outdoor work, consistently showed a higher risk of respiratory ERVs during hot weather compared to males. Younger workers (20-64 years old) exhibited a higher risk of ERVs, likely due to job profiles with greater exposure to extreme temperatures. Notably, the highest risk of all-causes ERVs was observed in outdoor male laborers (union members), followed by farmers and private employees, with the lowest risk among indoor workers. Conversely, female indoor workers and female farmers faced the highest risk of respiratory ERVs. Again, female farmers with consistent outdoor exposure had the highest risk of circulatory ERVs during cold conditions. CONCLUSION: Our findings highlighted the complexity of temperature-related health risks associated with different occupational contexts. The population-level insights into vulnerable occupational groups could provide valuable comprehension for policymakers and healthcare practitioners.

2.
MycoKeys ; 105: 217-251, 2024.
Article in English | MEDLINE | ID: mdl-38846425

ABSTRACT

Tea plant is one of the most important commercial crops worldwide. The Didymellaceae fungi can cause leaf blight disease of tea plant. In this study, 240 isolates were isolated from tea plant leaves of 10 provinces in China. Combined with multi-locus (ITS, LSU, RPB2 and TUB2) phylogenetic analysis and morphological characteristics, these isolates were identified as 25 species of six genera in Didymellaceae, including 19 known species Didymellacoffeae-arabicae, D.pomorum, D.segeticola, D.sinensis, Epicoccumcatenisporum, E.dendrobii, E.draconis, E.italicum, E.latusicollum, E.mackenziei, E.oryzae, E.poaceicola, E.rosae, E.sorghinum, E.tobaicum, Neoascochytamortariensis, Paraboeremialitseae, Remotididymellaanemophila and Stagonosporopsiscaricae, of which 15 species were new record species and six novel species, named D.yunnanensis, E.anhuiense, E.jingdongense, E.puerense, N.yunnanensis and N.zhejiangensis. Amongst all isolates, D.segeticola was the most dominant species. Pathogenicity tests on tea plant leaves showed that E.anhuiense had the strongest virulence, while E.puerense had the weakest virulence. Besides, D.pomorum, D.yunnanensis, E.dendrobii, E.italicum, E.jingdongense, E.mackenziei, E.oryzae, E.rosae, E.tobaicum, N.mortariensis, N.yunnanensis, N.zhejiangensis and R.anemophila were non-pathogenic to the tea plant.

3.
Viruses ; 16(6)2024 May 22.
Article in English | MEDLINE | ID: mdl-38932115

ABSTRACT

In this study, we investigated the concentration of airborne influenza virus in daycare centers and influencing factors, such as common cold prevalence, air pollutants, and meteorological factors. A total of 209 air samples were collected from daycare centers in Kaohsiung and the influenza virus was analyzed using real-time quantitative polymerase chain reaction. Air pollutants and metrological factors were measured using real-time monitoring equipment. Winter had the highest positive rates of airborne influenza virus and the highest prevalence of the common cold, followed by summer and autumn. The concentration of CO was significantly positively correlated with airborne influenza virus. Daycare center A, with natural ventilation and air condition systems, had a higher concentration of airborne influenza A virus, airborne fungi, and airborne bacteria, as well as a higher prevalence of the common cold, than daycare center B, with a mechanical ventilation system and air purifiers, while the concentrations of CO2, CO, and UFPs in daycare center A were lower than those in daycare center B. We successfully detected airborne influenza virus in daycare centers, demonstrating that aerosol sampling for influenza can provide novel epidemiological insights and inform the management of influenza in daycare centers.


Subject(s)
Air Microbiology , Child Day Care Centers , Influenza, Human , Seasons , Humans , Influenza, Human/epidemiology , Influenza, Human/virology , Influenza, Human/transmission , Influenza A virus/isolation & purification , Influenza A virus/genetics , Orthomyxoviridae/isolation & purification , Orthomyxoviridae/genetics , Air Pollutants/analysis , Common Cold/epidemiology , Common Cold/virology , Common Cold/transmission , Child, Preschool , Prevalence , Environmental Monitoring
4.
Planta ; 259(6): 147, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38714547

ABSTRACT

MAIN CONCLUSION: CsNAC086 was found to promote the expression of CsFLS, thus promoting the accumulation of flavonols in Camellia sinensis. Flavonols, the main flavonoids in tea plants, play an important role in the taste and quality of tea. In this study, a NAC TF gene CsNAC086 was isolated from tea plants and confirmed its regulatory role in the expression of flavonol synthase which is a key gene involved in the biosynthesis of flavonols in tea plant. Yeast transcription-activity assays showed that CsNAC086 has self-activation activity. The transcriptional activator domain of CsNAC086 is located in the non-conserved C-terminal region (positions 171-550), while the conserved NAC domain (positions 1-170) does not have self-activation activity. Silencing the CsNAC086 gene using antisense oligonucleotides significantly decreased the expression of CsFLS. As a result, the concentration of flavonols decreased significantly. In overexpressing CsNAC086 tobacco leaves, the expression of NtFLS was significantly increased. Compared with wild-type tobacco, the flavonols concentration increased. Yeast one-hybrid assays showed CsNAC086 did not directly regulate the gene expression of CsFLS. These findings indicate that CsNAC086 plays a role in regulating flavonols biosynthesis in tea plants, which has important implications for selecting and breeding of high-flavonols-concentration containing tea-plant cultivars.


Subject(s)
Camellia sinensis , Flavonols , Gene Expression Regulation, Plant , Nicotiana , Plant Proteins , Camellia sinensis/genetics , Camellia sinensis/metabolism , Flavonols/biosynthesis , Flavonols/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Nicotiana/genetics , Nicotiana/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Oxidoreductases/genetics , Oxidoreductases/metabolism , Plant Leaves/metabolism , Plant Leaves/genetics , Plants, Genetically Modified
5.
Environ Res ; 252(Pt 2): 118925, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38615795

ABSTRACT

Excessive levels of nitrate nitrogen (NO3--N) could lead to ecological issues, particularly in the Yarlung Tsangpo River (YTR) region located on the Qinghai Tibet Plateau. Therefore, it is crucial to understand the fate and sources of nitrogen to facilitate pollution mitigation efforts. Herein, multiple isotopes and source resolution models were applied to analyze key transformation processes and quantify the sources of NO3-. The δ15N-NO3- and δ18O-NO3- isotopic compositions in the YTR varied between 1.23‰ and 13.64‰ and -7.88‰-11.19‰, respectively. The NO3--N concentrations varied from 0.08 to 0.86 mg/L in the dry season and 0.20-1.19 mg/L during the wet season. Nitrification remained the primary process for nitrogen transformation in both seasons. However, the wet season had a widespread effect on increasing nitrate levels, while denitrification had a limited ability to reduce nitrate. The elevated nitrate concentrations during the flood season were caused by increased release of NO3- from manure & sewage (M&S) and chemical fertilizers (CF). Future endeavors should prioritize enhancing management strategies to improve the utilization efficiency of CF and hinder the direct entry of untreated sewage into the water system.


Subject(s)
Bayes Theorem , Environmental Monitoring , Nitrates , Rivers , Water Pollutants, Chemical , Nitrates/analysis , Rivers/chemistry , Environmental Monitoring/methods , Water Pollutants, Chemical/analysis , Tibet , Seasons , Denitrification
6.
Adv Sci (Weinh) ; : e2309639, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38682443

ABSTRACT

Targeting "undruggable" targets with intrinsically disordered structures is of great significance for the treatment of disease. The transcription factor c-Myc controls global gene expression and is an attractive therapeutic target for multiple types of cancers. However, due to the lack of defined ligand binding pockets, targeted c-Myc have thus far been unsuccessful. Herein, to address the dilemma of lacking ligands, an efficient and high throughput aptamer screening strategy is established, named polystyrene microwell plate-based systematic evolution of ligands by exponential enrichment (microwell-SELEX), and identify the specific aptamer (MA9C1) against c-Myc. The multifunctional aptamer-based Proteolysis Targeting Chimeras (PROTAC) for proteolysis of the c-Myc (ProMyc) is developed using the aptamer MA9C1 as the ligand. ProMyc not only significantly degrades c-Myc by the ubiquitin-proteasome system, but also reduces the Max protein, synergistically inhibiting c-Myc transcriptional activity. Combination of the artificial cyclization and anti-PD-L1 aptamer (PA1)-based delivery system, circular PA1-ProMyc chimeras achieve tumor regression in the xenograft tumor model, laying a solid foundation for the development of efficacious c-Myc degrader for the clinic. Therefore, this aptamer-based degrader provides an invaluable potential degrader in drug discovery and anti-tumor therapy, offering a promising degrader to overcome the challenge of targeting intractable targets.

7.
Acta Trop ; 253: 107170, 2024 May.
Article in English | MEDLINE | ID: mdl-38467234

ABSTRACT

Spatial analysis of infectious diseases can play an important role in mapping the spread of diseases and can support policy making at local level. Moreover, identification of disease clusters based on local geography and landscape forms the basis for disease control and prevention. Therefore, this study aimed to examine the spatial-temporal variations, hotspot areas, and potential risk factors of infectious diseases (including Viral Hepatitis, Typhoid and Diarrhea) in Ahmedabad city of India. We used Moran's I and Local Indicators of Spatial Association (LISA) mapping to detect spatial clustering of diseases. Spatial and temporal regression analysis was used to identify the association between disease incidence and spatial risk factors. The Moran's I statistics identified presence of positive spatial autocorrelation within the considered diseases, with Moran's I from 0.09 for typhoid to 0.21 for diarrhea (p < 0.001). This indicates a clustering of affected wards for each disease, suggesting that cases were not randomly distributed across the city. LISA mapping demonstrated the clustering of hotspots in central regions of the city, especially towards the east of the river Sabarmati, highlighting key geographical areas with elevated disease risk. The spatial clusters of infectious diseases were consistently associated with slum population density and illiteracy. Furthermore, temporal analysis suggested illiteracy rates could increase risk of viral hepatitis by 13 % (95 % Confidence Interval (CI): 1.01-1.26) and of diarrhea by 18 % (95 % CI: 1.07-1.31). Significant inverse association was also seen between viral hepatitis incidence and the distance of wards from rivers. Conclusively, the study highlight the impact of socio-economic gradients, such as slum population density (indicative of poverty) and illiteracy, on the localized transmission of water and foodborne infections. The evident social stratification between impoverished and affluent households emerges as a notable contributing factor and a potential source of differences in the dynamics of infectious diseases in Ahmedabad.


Subject(s)
Communicable Diseases , Hepatitis, Viral, Human , Typhoid Fever , Humans , Typhoid Fever/epidemiology , Health Planning , Spatial Analysis , Diarrhea/epidemiology , India/epidemiology , Water , Cluster Analysis
8.
Sci Rep ; 14(1): 7448, 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38548842

ABSTRACT

Climate change is closely monitored and numerous studies reports increasing air temperature and weather extremes across the globe. As a direct consequence of the increase of global temperature, the increased heat stress is becoming a global threat to public health. While most climate change and epidemiological studies focus on air temperature to explain the increasing risks, heat strain can be predicted using comprehensive indices such as Universal Thermal Climate Index (UTCI). The Asia-Pacific region is prone to thermal stress and the high population densities in the region impose high health risk. This study evaluated the air temperature and UTCI trends between 1990 and 2019 and found significant increasing trends for air temperature for the whole region while the increases of UTCI are not as pronounced and mainly found in the northern part of the region. These results indicate that even though air temperature is increasing, the risks of heat stress when assessed using UTCI may be alleviated by other factors. The associations between El Niño Southern Oscillation (ENSO) and heat stress was evaluated on a seasonal level and the strongest regional responses were found during December-January (DJF) and March-May (MAM).

9.
Eur J Med Res ; 29(1): 147, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38429734

ABSTRACT

BACKGROUND: The aim of the study was to investigate whether the expression of CD27-CD38+ in interferon (IFN)-γ+CD4+ T cells stimulated by the specific antigen early secreted antigenic target-6 (ESAT-6)/culture filter protein-10 (CFP-10) could be a potential new therapeutic evaluation indicator for anti-tuberculosis (TB) treatment. METHODS: Newly diagnosed active pulmonary TB patients, latent TB infection (LTBI) and healthy controls were enrolled from January 2021 to December 2021. PTB patients were treated by standard anti-TB regimen 2HREZ/4HR (2 months of isoniazid (H), rifampin (R), ethambutol (E), and pyrazinamide (Z) followed by 4 months of isoniazid (H) and rifampin (R)). The difference of CD27-CD38+ expression in IFN-γ+CD4+ T cells before treatment, 2 months after treatment, and 6 months after treatment were compared. RESULTS: Total 45 PTB patients, 38 LTBI cases and 43 healthy controls were enrolled. The expression of CD27-CD38+ decreased significantly after anti-TB treatment and was comparable with that in LTBI and healthy controls when the 6-month anti-TB treatment course was completed. The decline rate of CD27-CD38+ between 6 months after treatment and baseline was positively correlated with erythrocyte sedimentation rate (r = 0.766, P < 0.0001), C-reactive protein (r = 0.560, P = 0.003) and chest computerized tomography severity score (r = 0.632, P = 0.0005). The area under receiver operator characteristic curve of CD27-CD38+ in distinguish pulmonary TB patients before and after treatment was 0.779. CONCLUSION: The expression of CD27-CD38+ in ESAT-6/CFP-10 stimulated IFN-γ+CD4+T cells can well reflect the changes of the disease before and after anti-TB treatment, which is expected to be a potential new therapeutic evaluation index. Clinical Registry number chiCTR1800019966.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Pulmonary , Tuberculosis , Humans , Antitubercular Agents/pharmacology , Antitubercular Agents/therapeutic use , CD4-Positive T-Lymphocytes , Isoniazid/pharmacology , Isoniazid/therapeutic use , Isoniazid/metabolism , Rifampin/metabolism , Tuberculosis/diagnosis , Tuberculosis, Pulmonary/drug therapy
10.
PeerJ ; 12: e16833, 2024.
Article in English | MEDLINE | ID: mdl-38406290

ABSTRACT

Background: Domestic cats are important companion animals in modern society that live closely with their owners. Mislabeling of pet food can not only harm pets but also cause issues in areas such as religious beliefs and natural resource management. Currently, the cat food market is booming. However, despite the risk that mislabeling poses to cats and humans, few studies have focused on species misrepresentation in cat food products. Methods: To address this issue, we used DNA barcoding, a highly effective identification methodology that can be applied to even highly processed products. We targeted a short segment (~85 basepairs) of the mitochondrial 16S rRNA (16S) gene as a barcode and employed Sanger or next generation sequencing (NGS) to inspect 138 canned cat food products in the Taiwanese market. Results: We discovered that the majority of mislabeling incidents were related to replacement of tuna with other species. Moreover, our metabarcoding revealed that numerous undeclared ingredients were present in all examined canned products. One product contained CITES Appendix II-listed shortfin mako shark (Isurus oxyrinchus). Overall, we uncovered a mislabeling rate of at least 28.99%. To verify cases of mislabeling, an official standardized list of vernacular names, along with the corresponding scientific species names, as well as a dependable barcoding reference sequence database are necessary.


Subject(s)
Animal Feed , DNA , Humans , Cats , Animals , RNA, Ribosomal, 16S/genetics , Taiwan , Seafood , Proteins
11.
Sci Total Environ ; 921: 171213, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38401737

ABSTRACT

Urban greenery can help to improve air quality, reduce health risks and create healthy livable urban communities. This study aimed to explore the role of urban greenery in reducing air pollution at the community level in Tainan City, Taiwan, using air quality sensors and street-view imagery. We also collected the number of road trees around each air quality sensor site and identified the species that were best at absorbing PM2.5. Three greenness metrics were used to assess community greenery in this study: two Normalized Difference Vegetation Indices (NDVI) from different satellites and the Green View Index (GVI) from Google Street View (GSV) images. Land-use Regression (LUR) was used for statistical analysis. The results showed that a higher GVI within a 500 m buffer was significantly associated with decreased PM2.5. Neither NDVI metrics within a 500 m circular buffer were significantly associated with decreased PM2.5. Evergreen trees were significantly associated with lower ambient PM2.5, compared with deciduous and semi-deciduous trees. Because localized changes in air quality profoundly affect public health and environmental equity, our findings provide evidence for future urban community greenspace planning and its beneficial impacts on reducing air pollution.


Subject(s)
Air Pollutants , Air Pollution , Particulate Matter/analysis , Air Pollutants/analysis , Air Pollution/analysis , Cities , City Planning , Environmental Exposure/analysis
12.
Int. microbiol ; 27(1): 67-79, Feb. 2024. ilus, graf
Article in English | IBECS | ID: ibc-230244

ABSTRACT

Complete ammonia oxidation (comammox) bacteria can complete the whole nitrification process independently, which not only challenges the classical two-step nitrification theory but also updates long-held perspective of microbial ecological relationship in nitrification process. Although comammox bacteria have been found in many ecosystems in recent years, there is still a lack of research on the comammox process in rhizosphere of emergent macrophytes in lakeshore zone. Sediment samples were collected in this study from rhizosphere, far-rhizosphere, and non-rhizosphere of emergent macrophytes along the shore of Lake Liangzi, a shallow lake. The diversity of comammox bacteria and amoA gene abundance of comammox bacteria, ammonia-oxidizing archaea (AOA), and ammonia-oxidizing bacteria (AOB) in these samples were measured. The results showed that comammox bacteria widely existed in the rhizosphere of emergent macrophytes and fell into clade A.1, clade A.2, and clade B, and clade A was the predominant community in all sampling sites. The abundance of comammox amoA gene (6.52 × 106–2.45 × 108 copies g−1 dry sediment) was higher than that of AOB amoA gene (6.58 × 104–3.58 × 106 copies g−1 dry sediment), and four orders of magnitude higher than that of AOA amoA gene (7.24 × 102–6.89 × 103 copies g−1 dry sediment), suggesting that the rhizosphere of emergent macrophytes is more favorable for the growth of comammox bacteria than that of AOB and AOA. Our study indicated that the comammox bacteria may play important roles in ammonia-oxidizing processes in all different rhizosphere regions.(AU)


Subject(s)
Humans , Rhizosphere , Soil Microbiology , Ammonia , Lakes/microbiology , Archaea , Oxidation-Reduction , Microbiology , Microbiological Techniques , Ecosystem
13.
Plant J ; 117(5): 1356-1376, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38059663

ABSTRACT

Tea plant [Camellia sinensis (L.) O. Kuntze], as one of the most important commercial crops, frequently suffers from anthracnose caused by Colletotrichum camelliae. The plant-specific tau (U) class of glutathione S-transferases (GSTU) participates in ROS homeostasis. Here, we identified a plant-specific GST tau class gene from tea plant, CsGSTU45, which is induced by various stresses, including C. camelliae infection, by analyzing multiple transcriptomes. CsGSTU45 plays a negative role in disease resistance against C. camelliae by accumulating H2 O2 . JA negatively regulates the resistance of tea plants against C. camelliae, which depends on CsGSTU45. CsMYC2.2, which is the key regulator in the JA signaling pathway, directly binds to and activates the promoter of CsGSTU45. Furthermore, silencing CsMYC2.2 increased disease resistance associated with reduced transcript and protein levels of CsGSTU45, and decreased contents of H2 O2 . Therefore, CsMYC2.2 suppresses disease resistance against C. camelliae by binding to the promoter of the CsGSTU45 gene and activating CsGSTU45. CsJAZ1 interacts with CsMYC2.2. Silencing CsJAZ1 attenuates disease resistance, upregulates the expression of CsMYC2.2 elevates the level of the CsGSTU45 protein, and promotes the accumulation of H2 O2 . As a result, CsJAZ1 interacts with CsMYC2.2 and acts as its repressor to suppress the level of CsGSTU45 protein, eventually enhancing disease resistance in tea plants. Taken together, the results show that the JA signaling pathway mediated by CsJAZ1-CsMYC2.2 modulates tea plant susceptibility to C. camelliae by regulating CsGSTU45 to accumulate H2 O2 .


Subject(s)
Camellia sinensis , Colletotrichum , Cyclopentanes , Oxylipins , Camellia sinensis/genetics , Camellia sinensis/metabolism , Glutathione Transferase/genetics , Glutathione Transferase/metabolism , Disease Resistance/genetics , Colletotrichum/physiology , Tea/metabolism , Signal Transduction
14.
Int Microbiol ; 27(1): 67-79, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38062210

ABSTRACT

Complete ammonia oxidation (comammox) bacteria can complete the whole nitrification process independently, which not only challenges the classical two-step nitrification theory but also updates long-held perspective of microbial ecological relationship in nitrification process. Although comammox bacteria have been found in many ecosystems in recent years, there is still a lack of research on the comammox process in rhizosphere of emergent macrophytes in lakeshore zone. Sediment samples were collected in this study from rhizosphere, far-rhizosphere, and non-rhizosphere of emergent macrophytes along the shore of Lake Liangzi, a shallow lake. The diversity of comammox bacteria and amoA gene abundance of comammox bacteria, ammonia-oxidizing archaea (AOA), and ammonia-oxidizing bacteria (AOB) in these samples were measured. The results showed that comammox bacteria widely existed in the rhizosphere of emergent macrophytes and fell into clade A.1, clade A.2, and clade B, and clade A was the predominant community in all sampling sites. The abundance of comammox amoA gene (6.52 × 106-2.45 × 108 copies g-1 dry sediment) was higher than that of AOB amoA gene (6.58 × 104-3.58 × 106 copies g-1 dry sediment), and four orders of magnitude higher than that of AOA amoA gene (7.24 × 102-6.89 × 103 copies g-1 dry sediment), suggesting that the rhizosphere of emergent macrophytes is more favorable for the growth of comammox bacteria than that of AOB and AOA. Our study indicated that the comammox bacteria may play important roles in ammonia-oxidizing processes in all different rhizosphere regions.


Subject(s)
Ammonia , Archaea , Archaea/genetics , Rhizosphere , Ecosystem , Lakes/microbiology , Oxidation-Reduction , Phylogeny , Bacteria , Soil Microbiology
15.
Lupus Sci Med ; 10(2)2023 11 22.
Article in English | MEDLINE | ID: mdl-37993281

ABSTRACT

OBJECTIVES: The study aims to investigate the impact of gene polymorphisms on blood hydroxychloroquine (HCQ) concentrations in patients with SLE and provide guidelines for individualised care. METHODS: 489 Chinese patients with SLE taking HCQ for more than 3 months were collected in this study. The blood HCQ, desethylhydroxychloroquine (DHCQ) and desethylchloroquine concentrations were measured. The optimal blood concentration of HCQ was determined by receiver operating characteristic curve analysis. Single nucleotide polymorphisms of metabolic enzymes involved in HCQ metabolism were genotyped and the associations with treatment effects were investigated. RESULTS: The cut-off value of HCQ was 559.67 ng/mL, with sensitivity and specificity values of 0.51 and 0.89, respectively. The TC and CC genotypes of CYP2C8 (rs7910936) were significantly related to the increase in blood HCQ concentrations, and the CYP2C8 (rs10882521) TT genotype was associated with lower blood HCQ concentrations. The DHCQ:HCQ ratio was highest in patients with the GG genotype of the CYP2D6*10 (rs1065852) polymorphism and lowest in those with the AA genotype. Patients with the CYP2C8 (rs7910936) CC genotype were more likely to achieve the optimal blood concentration (p=0.030) in HCQ 200 mg/day group and patients with the CYP2D6*10 (rs1065852) GG genotype were more likely to reach the optimal blood concentration (p=0.049) in 400 mg/day group. CONCLUSIONS: Our results suggest that the optimal blood concentration of HCQ measured approximately 12-18 hours after the last dosage may be between 500 and 600 ng/mL in Chinese patients with SLE. The observed variations in HCQ concentrations between individuals can potentially be attributed to genetic polymorphisms in CYP2D6*10 (rs1065852) and CYP2C8 (rs7910936 and rs10882521). Genotypical testing of patients and regular monitoring of blood levels are recommended for optimising HCQ dosage management in Chinese patients with SLE. TRIAL REGISTRATION NUMBER: ChiCTR2300070628.


Subject(s)
Antirheumatic Agents , Lupus Erythematosus, Systemic , Humans , Hydroxychloroquine/therapeutic use , Antirheumatic Agents/therapeutic use , Cytochrome P-450 CYP2C8 , Cytochrome P-450 CYP2D6/genetics , East Asian People , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/genetics , Genotype
16.
Cell Chem Biol ; 30(11): 1390-1401.e6, 2023 11 16.
Article in English | MEDLINE | ID: mdl-37944524

ABSTRACT

Checkpoint inhibitor antibody therapy by blocking the interaction of surface programmed death-ligand 1(PD-L1) and programmed cell death protein 1(PD-1) has promising advantages in cancer immunotherapy. However, the response of many patients remains unsatisfactorily, suspected to be relevant to PD-L1 located in other cellular compartments and antibodies do not have access to the intracellular compartments. Herein, we identify a PD-L1-targeting DNA aptamer (PA9-1) with dual roles, including an antagonist and a delivery agent dependent on PD-L1 internalization. And we design the PD-L1-targeting antagonistic aptamer-ASO delivery system (PA9-1-ASO), with synergistic inhibitory PD-L1 activity involving the combination of blockade and silencing mechanisms. This chimera not only blocks PD-L1/PD-1 but also achieves targeted delivery of the conjugated ASO to reduce both surface PD-L1 and total PD-L1 expression. Compared with the single blockade, this chimera with the dual inhibitory function synergistically inhibits PD-L1 to amplify immunotherapeutic efficacy, providing a promising synergistic strategy for immunotherapy.


Subject(s)
B7-H1 Antigen , Neoplasms , Humans , B7-H1 Antigen/therapeutic use , Programmed Cell Death 1 Receptor , Neoplasms/drug therapy , Immunotherapy
17.
Environ Sci Pollut Res Int ; 30(60): 126045-126056, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38008835

ABSTRACT

In the last few decades, U(VI) is a significant environmental threat. The innovative and environmentally friendly adsorbent materials for U(VI) removal were urgent. Preparation of the modified biochar from wheat straw by combined composites of MnFe2O4 nanoparticles and chitosan Schiff base (MnFe2O4@CsSB/BC) was characterized, and adsorption experiments were carried out to investigate the performance and interfacial mechanism of U(VI) removal. The results showed that MnFe2O4@CsSB/BC exhibited high adsorption capacity of U(VI) compared with BC. The adsorption process of U(VI) removal by MnFe2O4@CsSB/BC could be ascribed as pseudo-second-order model and Langmuir model. The maximum adsorption capacity of U(VI) removal by MnFe2O4@CsSB/BC reached 19.57 mg/g at pH4.0, 30 mg/L of U(VI), and 25 °C. The possible mechanism was a chemical adsorption process, and it mainly contained electrostatic attraction and surface complexation. Additionally, it also was an economic and environmental friendly adsorbent.


Subject(s)
Chitosan , Nanoparticles , Water Pollutants, Chemical , Chitosan/chemistry , Triticum , Schiff Bases , Water/chemistry , Nanoparticles/chemistry , Charcoal/chemistry , Adsorption , Water Pollutants, Chemical/analysis , Kinetics , Chromium/chemistry
18.
Environ Res ; 239(Pt 2): 117365, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-37838202

ABSTRACT

The water environment of large reservoirs is fragility due to effects from hydrological regulation of damming and anthropogenic inputs. As a critical path to quantify the natural chemical weathering and assess environmental risks, solute chemistry of river has been widely focused on. However, the complexed hydrological conditions of large reservoir affect the chemical compositions, and the significance of solute vertical geochemistry as an indicator of chemical weathering and water quality health remains explore. Therefore, the Three Gorges Reservoir (TGR) was selected as a typical study area, which is the world's largest hydropower project and subject to frequent water quality problems. Then, the chemical compositions in stratified water were determined. Ca2+ (52.8 ± 4.3 mg/L) and HCO3- (180.9 ± 8.9 mg/L) were the most abundant ions among cations and anions, respectively. Incremental mean concentration of total major ions followed with the increase of riverine depth and flow direction. An improved inversion model was used to quantify the source contribution, which weathering of dolomite (34%) and calcite (38%) contributed the most to total cations, and the influences of agriculture and sewage discharge were limited. Additional contributions of evaporite and pyrite oxidation were found in analysis of deeper water samples, which also results in 2%-67% difference in estimated CO2 release flux using data from different depth, indicating additional information about sulfuric acid driven weathering was contained. Finally, the water quality of the reservoir was assessed for irrigation and non-carcinogenic risks. Results showed the stratified water of TGR can be used as a good water source of irrigation. However, NO3- (5.1 ± 1.1 mg/L) may have a potential non-carcinogenic risk to children, especially in surface water. To sum up, this study provided an indispensable supplement to the water chemistry archives in the TGR basin, serving as theoretical references for environmental management of large reservoirs.


Subject(s)
Environmental Monitoring , Water Pollutants, Chemical , Child , Humans , Environmental Monitoring/methods , Water Quality , Rivers/chemistry , Weather , Cations/analysis , Water Pollutants, Chemical/analysis , China
19.
Nat Commun ; 14(1): 5897, 2023 09 22.
Article in English | MEDLINE | ID: mdl-37736771

ABSTRACT

Tuberculosis continues to pose a serious threat to global health. Mycobacterium tuberculosis, the causative agent of tuberculosis, is an intracellular pathogen that relies on various mechanisms to survive and persist within the host. Among their many virulence factors, mycobacteria encode Mce systems. Some of these systems are implicated in lipid uptake, but the molecular basis for Mce function(s) is poorly understood. To gain insights into the composition and architecture of Mce systems, we characterized the putative Mce1 complex involved in fatty acid transport. We show that the Mce1 system in Mycobacterium smegmatis comprises a canonical ATP-binding cassette transporter associated with distinct heterohexameric assemblies of substrate-binding proteins. Furthermore, we establish that the conserved membrane protein Mce1N negatively regulates Mce1 function via a unique mechanism involving blocking transporter assembly. Our work offers a molecular understanding of Mce complexes, sheds light on mycobacterial lipid metabolism and its regulation, and informs future anti-mycobacterial strategies.


Subject(s)
Membrane Proteins , Mycobacterium tuberculosis , Membrane Proteins/genetics , Mycobacterium smegmatis/genetics , Mycobacterium tuberculosis/genetics , Membrane Transport Proteins , ATP-Binding Cassette Transporters/genetics
20.
Acta Neurol Taiwan ; 32(4): 202-206, 2023 Dec 30.
Article in English | MEDLINE | ID: mdl-37723912

ABSTRACT

PURPOSE: While the gustatory pathway of animals has been well-researched, that of humans is still a mystery. Several theories have been established, and some earlier reports hypothesized the relation to laterality. However, some cases could not be fully explained by the laterality theory (1). To clarify the gustatory pathway, we reported a case with bilateral hypogeusia after right thalamic infarction. CASE: This 55-year-old, right-handed man suffered from sudden decreased sensitivity of taste. He was unable to differentiate sweetness and saltiness at bilateral anterior parts of tongue. Additionally, there was numbness at the upper palate and the lips. Neurological examination revealed decreased taste sense at both sides of his anterior tongue and decreased pin-prick sensation of the left part of his lips. Brain magnetic resonance imaging (MRI) revealed acute ischemic stroke at the right ventral posteromedial nucleus (VPM). Thus, single antiplatelet therapy was administered. Two weeks later, the symptoms improved significantly and completely recovered without sequelae. CONCLUSION: The exact gustatory pathway in humans remains uncertain nowadays. First, there were few reports about dysgeusia, which might be related to clinical neglect of taste deficits. Second, our knowledge of the human gustatory pathway depends solely on sporadic cases of taste-involved brain lesions. We reported a case of bilateral hypogeusia after right thalamic infarction. This finding indicates that, although there might be laterality of gustatory fibers to the left hemisphere, anatomical variations may exist in the human gustatory system. More research is needed to elucidate the understanding of the gustatory pathway in humans.


Subject(s)
Ageusia , Ischemic Stroke , Stroke, Lacunar , Animals , Male , Humans , Middle Aged , Ageusia/etiology , Thalamus/diagnostic imaging , Ventral Thalamic Nuclei , Cerebral Infarction/complications , Cerebral Infarction/diagnostic imaging
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