A functional study reveals CsNAC086 regulated the biosynthesis of flavonols in Camellia sinensis.

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.

Nitrate transformation and source tracking of Yarlung Tsangpo River using a multi-tracer approach combined with Bayesian stable isotope mixing model.

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.

Antitumor Effect of Anti-c-Myc Aptamer-Based PROTAC for Degradation of the c-Myc Protein.

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.

Spatiotemporal link between El Niño Southern Oscillation (ENSO), extreme heat, and thermal stress in the Asia-Pacific region.

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).

Spatial analysis of food and water-borne diseases in Ahmedabad, India: Implications for urban public health planning.

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.

Changes of Mycobacterium tuberculosis specific antigen-stimulated CD27-CD38+IFN-γ+CD4+ T cells before and after anti-tuberculosis treatment.

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.

DNA mini-barcoding reveals the mislabeling rate of canned cat food in Taiwan.

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.

Associations between community green view index and fine particulate matter from Airboxes.

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.

The abundance of comammox bacteria was higher than that of ammonia-oxidizing archaea and bacteria in rhizosphere of emergent macrophytes in a typical shallow lake riparian / La abundancia de bacterias comammox fue mayor que la de arqueas y bacterias oxidantes de amoníaco en la rizosfera de macrófitos emergentes en un típico lago ribereño poco profundo

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)

The abundance of comammox bacteria was higher than that of ammonia-oxidizing archaea and bacteria in rhizosphere of emergent macrophytes in a typical shallow lake riparian.

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.

A tau class glutathione S-transferase in tea plant, CsGSTU45, facilitates tea plant susceptibility to Colletotrichum camelliae infection mediated by jasmonate signaling pathway.

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 .

Anti-tumor effect of PD-L1-targeting antagonistic aptamer-ASO delivery system with dual inhibitory function in immunotherapy.

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.

The modified biochar from wheat straw by the combined composites of MnFe2O4 nanoparticles and chitosan Schiff base for enhanced removal of U(VI) ions from aqueous solutions.

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.

Genotype-guided new approach for dose optimisation of hydroxychloroquine administration in Chinese patients with SLE.

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.

Effect of damming on hydrogeochemical characteristics and potential environmental risks in a large reservoir: Insights from different vertical layer sampling.

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.

A conserved membrane protein negatively regulates Mce1 complexes in mycobacteria.

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.

Spatial variation of soil phosphorus in the water level fluctuation zone of the Three Gorges Reservoir: Coupling effects of elevation and artificial restoration.

The water level fluctuation zone (WLFZ) is a distinctive and important component of the reservoir ecosystem. Due to periodic inundation, the fraction, spatial distribution, and chemical reactivity of soil phosphorus (P) within the WLFZ can potentially impact the loading of P into reservoir waters. However, a detailed study of this subject is lacking. In this study, the soil P in the WLFZ of the Three Gorges Reservoir, China, was examined using a combination of chemical sequential extraction, 31P NMR, and adsorption experiments. The results of chemical sequential extraction showed that HCl-Pi constituted the largest P pool among all P forms, with a mean concentration of 338 mg/kg. The content of HCl-Pi decreased significantly toward the dam, while the content of Res-P decreased in the opposite direction. The highest contents of most P forms and total P were observed at an elevation of 160 m. 31P NMR measurements showed that NaOH-EDTA Pi detectable in WLFZ soils at 145 m, 160 m, and 175 m elevation consisted mainly of orthophosphate and pyrophosphate, while NaOH-EDTA Po contained phosphate monoesters and phosphate diesters, accounting for 1.4 % to 46.2 % of NaOH-EDTA TP. Adsorption experiments showed that soil P in the WLFZ was a potential P source for reservoir waters, with chemisorption being the dominant mechanism of P sequestration. The adsorption equilibrium concentration of WLFZ soil was lower at higher elevations (>170 m) compared to lower elevations (<150 m), exhibiting a decrease in the average maximum adsorption from 271 mg/kg to 192 mg/kg. Statistical analysis suggested that Ca and Fe content, particle size, elevation, and artificial restoration were key factors affecting the fraction and content of soil P in the WLFZ. Our findings contribute to an improved understanding of the behavior of soil P in the WLFZ of large reservoirs and its potential contribution to the reservoir waters.

Pure Sensory Lacunar Infarction in the Thalamus Presented as Bilateral Hypogeusia: A Case Report.

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.

Retrospective analysis and preliminary laboratory validation of treatment efficacy and blood lipid levels in patients with rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis is a systemic disease characterized by progressive chronic inflammation resulting in destruction of synovial joints. In addition to joint involvement, abnormal blood lipid indexes have also been found in RA patients. The correlation between various blood lipid indexes and the treatment effects were assessed in patients with rheumatoid arthritis, for the purposes to find a better medication strategy for RA. METHODS: One hundred nineteen rheumatoid arthritis patients were recruited and divided into two groups, 45 patients with significant drug treatment effect and 45 patients with insignificant drug treatment effect through the nearest neighbor matching method in propensity score. The correlation between various blood lipid indexes and drug treatment effect of rheumatoid arthritis patients was analyzed. A mouse model of rheumatoid arthritis was constructed in the laboratory; methotrexate was treated as a positive drug. We observe and record the onset of rheumatoid arthritis in mice, as well as the proportion of immune cells, the expression of inflammatory factors, and the changes in blood lipid profiles was done. RESULTS: The levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), and erythrocyte sedimentation rate (ESR) in rheumatoid arthritis patients were significantly different between the two groups (P < 0.05). There was no significant difference in other indexes between the two groups (P > 0.05). Methotrexate had a good therapeutic effect on CIA model mice, and the levels of TC and HDL-C in the treatment group were higher than those in the model group. CONCLUSION: There is a high correlation between the levels of TC and HDL-C in rheumatoid arthritis patients and the effect of drug treatment. In the clinical treatment of rheumatoid arthritis, we should focus on improving the blood lipid indexes such as TC and HDL-C, and explore more targeted individualized administration, so as to achieve better and faster treatment effect in patients with rheumatoid arthritis. Key Points • In this research, we found that the TC and HDL-C level in RA patients' blood is highly related with the therapeutic effect, and a lower level of TC and HDL-C is better for therapeutic effect of RA.

Extreme precipitation patterns in the Asia-Pacific region and its correlation with El Niño-Southern Oscillation (ENSO).

In the Asia-Pacific region (APR), extreme precipitation is one of the most critical climate stressors, affecting 60% of the population and adding pressure to governance, economic, environmental, and public health challenges. In this study, we analyzed extreme precipitation spatiotemporal trends in APR using 11 different indices and revealed the dominant factors governing precipitation amount by attributing its variability to precipitation frequency and intensity. We further investigated how these extreme precipitation indices are influenced by El Niño-Southern Oscillation (ENSO) at a seasonal scale. The analysis covered 465 ERA5 (the fifth-generation atmospheric reanalysis of the European Center for Medium-Range Weather Forecasts) study locations over eight countries and regions during 1990-2019. Results revealed a general decrease indicated by the extreme precipitation indices (e.g., the annual total amount of wet-day precipitation, average intensity of wet-day precipitation), particularly in central-eastern China, Bangladesh, eastern India, Peninsular Malaysia and Indonesia. We observed that the seasonal variability of the amount of wet-day precipitation in most locations in China and India are dominated by precipitation intensity in June-August (JJA), and by precipitation frequency in December-February (DJF). Locations in Malaysia and Indonesia are mostly dominated by precipitation intensity in March-May (MAM) and DJF. During ENSO positive phase, significant negative anomalies in seasonal precipitation indices (amount of wet-day precipitation, number of wet days and intensity of wet-day precipitation) were observed in Indonesia, while opposite results were observed for ENSO negative phase. These findings revealing patterns and drivers for extreme precipitation in APR may inform climate change adaptation and disaster risk reduction strategies in the study region.