Ozone containment through selective mitigation measures on precursors of volatile organic compounds.

Abatement of volatile organic compounds (VOCs) ozone reduction is usually carried out by reducing the total amount of VOCs without considering reactivity between different species. This study incorporates the concept of maximum incremental reactivity (MIR) and speciation profiles into the industrial emission inventory of Taiwan to target organic species from industrial sources with the greatest ozone formation potentials (OFPs). These high OFP sources/species are then mitigated to assess the O3 reduction amount (ΔO3) with Community Multiscale Air Quality (CMAQ) modeling under VOC-limited conditions. The objective is to minimize the number of target sources/species and their tonnage while achieving maximum O3 reduction. This approach is referred to as the Selective Precursor Mitigation (SPM). A case study of a high ozone episode (September 4-10, 2020) was chosen for illustration, during which a relatively stagnant atmospheric condition with minimal transboundary ozone occurred. A series of scenarios to target the highest OFP chemicals/industries for mitigation are compared for the achievable max. ΔO3, areas affected (area coverage), and reduction efficiency. For instance, by reducing the ten leading industry classes with the island's highest OFPs (OFPind), up to 19 % of max. 1-h ΔO3 can be expected. If, however, the same tonnage of VOCs as that of OFPind is distributed to all industries without considering the reactivity, called the overall mitigation (OM), comparable results to those of OFPind were found, but the number of sources needed to be managed with OM would increase by nearly three times (29,662 for OM vs. 11,981 for OFPind). Further reducing the management scale by only zooming in the ten highest OFP chemicals within the ten leading OFP industries (OFPsp) would result in relatively limited area coverage. Still, major ozone hot spots could be alleviated. Although the domain is set on the island of Taiwan, the SPM approach is universally applicable to other regions worldwide to gain the maximum ozone reduction effect at a minimized societal cost.

GRACE-based groundwater drought in the Indochina Peninsula during 1979-2020: Changing properties and possible teleconnection mechanisms.

Groundwater is very important for human productivity and daily life, hydrological cycle regulation, and ecosystem stability. However, due to the complex mechanisms of groundwater drought, the spatial and temporal variations of groundwater drought and its driving mechanisms are still not fully understood, especially in Indochina Peninsula. In this work, we used a reconstructed long-term terrestrial water storage dataset from the Gravity Recovery and Climate Experiment (GRACE) emission and a GRACE-based groundwater drought index to investigate the spatial and temporal characteristics of groundwater drought during 1979-2020 in the Indochina Peninsula. The possible teleconnection mechanisms between groundwater drought and the Indian Ocean Dipole (IOD), El Niño-Southern Oscillation (ENSO), and El Niño Modoki (ENSO_M) were also investigated using cross wavelet transform method. The results show that groundwater drought worsens significantly during 1979-2020, and becomes much more frequent and intensified after 2000 in the southern Indochina Peninsula. Both univariate and bivariate (logic 'or' and 'and') return periods for duration, severity, and peak of groundwater drought are short in the southern Indochina Peninsula, and thus the risk of groundwater drought is high. The IOD, ENSO, and ENSO_M can reduce the intensity of groundwater drought to a certain extent during the warm phases, but only ENSO_M tends to significantly exacerbate the intensity of groundwater drought during the cold phases in the southern Indochina Peninsula. The variations in groundwater drought are dominated by ENSO_M, and are also coupled influenced by the IOD and ENSO in the southern Indochina Peninsula. The results provide valuable information for the sustainable ecological environment and socioeconomic development, especially development of groundwater drought early warning and prediction models in the Indochina Peninsula.

Exploring reduced macrophage cell toxicity of hypervirulent Klebsiella pneumoniae compared to classical Klebsiella pneumoniae.

Bacterial pneumoniae caused by Klebsiella pneumoniae (Kp) is a major concern due to the prevalence of multiple antibiotic-resistant strains, which limit treatment options and increase mortality rates. Patients with Kp infections often experience an uncontrolled immune response in the lungs, leading to excessive inflammation and elevated levels of proinflammatory cytokines. This study aimed to investigate the cytotoxicity, the inflammatory cytokine response, and the longevity of intracellular bacterial load in RAW 264.7 macrophages, infected with two different Kp strains - cKP (HKU1: Classical Kp) and HvKP (17ZR101: Hypervirulent Kp). This study found that after infecting macrophages with cKP and HvKP, the internalization rate was faster and the intracellular cKP load was higher than that of HvKP. Additionally, the number of intracellular Kp was correlated with the presence of M1 macrophage polarization marker CD86 and expressions of proinflammatory cytokines. Interestingly, the expression of these proinflammatory cytokines was significantly higher in cKP-infected macrophages than in HvKP-infected macrophages. Thus, a higher intracellular cKP load is suggested to play a significant role in causing more proinflammatory cytokines and killing macrophages compared to HvKP infection. This finding highlights the importance of understanding the mechanisms behind Kp infections and developing effective treatment strategies.

Characterization of VIM-71, a novel VIM-type metallo-ß-lactamase variant encoded by an integrative and conjugative element recovered from a Vibrio alginolyticus strain in China.

A novel VIM-type metallo-ß-lactamase variant, VIM-71, which is encoded by a multidrug-resistant Vibrio alginolyticus strain recovered from a shrimp sample in China, was identified. Compared to VIM-1, VIM-71 differs in 22 amino acid positions based on the primary protein sequence and confers a similar resistance profile to penicillins, but the level of resistance to carbapenems encoded by this enzyme was lower than that of VIM-1. The blaVIM-71 gene was found located in an integrative and conjugative element of the SXT/R391 family in the chromosome. These findings implied that genetic elements that encode clinically important carbapenemases continue to evolve in Vibrio spp.

Impact of Hepatocellular Carcinoma Tumor Size on Sonazoid Contrast-Enhanced Ultrasound Enhancement Features.

OBJECTIVE: The aim of the work described here was to evaluate the impact of hepatocellular carcinoma (HCC) tumor size on Sonazoid contrast-enhanced ultrasound (CEUS) enhancement features, especially in tumors with diameters ≤30 mm and <10 mm. METHODS: In this retrospective study, we included patients with histopathologically confirmed HCC lesions and divided them into three groups on the basis of tumor size. All patients underwent Sonazoid-enhanced CEUS examinations before surgery. B-mode ultrasound (BMUS) features and CEUS enhancement patterns were evaluated according to current World Federation for Ultrasound in Medicine and Biology Guidelines criteria. The χ2- and Student t-tests were used to compare differences between groups. RESULTS: We included 132 patients with histopathologically confirmed HCC lesions from November 2020 to September 2022. On the basis of tumor size, patients were divided into group 1 (<10 mm, n = 5), group 2 (10-30 mm, n = 54) and group 3 (>30 mm, n = 73). On BMUS, most HCCs appeared heterogeneous but predominantly hypo-echoic (61.4%, 81/132) with ill-defined margins and irregular shapes. Meanwhile, iso-echoic features were more common in small HCCs ≤30 mm (15.3%, 9/59), but a mixed hyper- and hypo-echoic appearance was more common in HCCs >30 mm (17.8%, 13/73) (p = 0.003). On Sonazoid-enhanced CEUS, all HCCs presented arterial phase hyperenhancement (APHE) (100.0%, 132/132). Most HCCs >30 mm exhibited heterogeneous hyperenhancement (86.3%, 63/73), whereas nearly one-third of small HCCs ≤30 mm exhibited homogeneous hyperenhancement (35.6%, 21/59) (p = 0.003). In the portal venous phase, there was a significantly higher proportion of washout in HCCs >30 mm (84.9%, 62/73) than in small HCCs ≤30 mm (64.4%, 38/59) (p = 0.006). During the Kupffer phase, 11 additional hypo-enhanced lesions (mean size: 14.1 ± 4.1 mm, iso-echoic on BMUS), which were also suspected to be HCC lesions, were detected in 5 patients with small HCCs ≤30 mm and 4 patients with HCCs >30 mm. All 5 cases of HCCs <10 mm exhibited APHE and late washout (>60 s). The majority (3/5, 60%) exhibited washout in the portal venous phase (70, 74 and 75 s), one case did so in the late phase (125 s) and another in the Kupffer phase (420 s). CONCLUSION: Tumor size had a significant impact on the washout features of HCC lesions on Sonazoid-enhanced CEUS. Small HCC lesions ≤30 mm had a higher proportion of relatively late washout in comparison to larger lesions. Sonazoid-enhanced CEUS might be helpful in the detection and characterization of HCC lesions <10 mm.

Conjugative plasmids facilitate the transmission of tmexCD2-toprJ2 among carbapenem-resistant Klebsiella pneumoniae.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a great threat to global public health. The emergence of tmexCD-toprJ greatly weakened the efficacy of tigecycline in the treatment of CRKP infections. In this study, we did a comprehensive investigation of the prevalence and genomic features of tmexCD-toprJ in clinical CRKP from 2018 to 2020 in Henan province, China. The results demonstrated tmexCD-toprJ was at a low prevalence in CRKP from patients (7/2031, 0.34 %). Among the seven tmexCD-toprJ positive CRKP, KP18-29 that carried tmexCD1-toprJ1, blaNDM-1 and mcr-8.2 was resistant to tigecycline, carbapenem and colistin simultaneously. While, tmexCD2-toprJ2 together with one or two carbapenemase genes were detected in the remaining strains. Four strains (KP18-231, KP18-2110-2, KP19-3023 and KP19-3088) isolated at different times but shared the same sequence type (ST) 2667 exhibited high genomic similarity, indicating the clonal dissemination of CRKP ST2667 co-producing KPC-2 and TMexCD-TOprJ. Notably, conjugative transmission of the IncFrepB(R1701) plasmid co-harboring tmexCD2-toprJ2 and blaKPC-2 among clinical CRKP isolates belonging to different STs (ST2667, ST978 and ST147) revealed further propagation of tmexCD-toprJ among K. pneumoniae. Such IncFrepB(R1701) plasmids pose a substantial threat to public health due to their mobile resistance to both tigecycline and carbapenem. Online data mining showed isolates carried both carbapenemase genes and tmexCD-toprJ were dominantly isolated from humans, and isolates of animal origins usually carried mcr genes and tmexCD-toprJ, suggesting that these critical resistance genes co-existed in diverse niches. Global surveillance of K. pneumoniae co-harboring tmexCD-toprJ and mcr/carbapenemase genes in various settings with a One Health strategy was warranted.

Full sexual maturity-cycle exposure to environmentally relevant concentrations of 17ß-estradiol decreases reproductive capacity of zebrafish.

17ß-Estradiol (E2) has been widely detected in natural water and treatment with E2 induces potential endocrine disrupting effects in fish. However, effects on fish fecundity and steroid system after treatment with environmentally relevant concentrations of E2 for the full sexual maturation cycle remain unclear. In this study, zebrafish were treatment with 0, 10 or 100 ng/L E2 from embryo to adult stage, and effects on gonadal development and differentiation, steroid hormone levels, transcription of genes associated with the hypothalamic-pituitary-gonadal-liver (HPG) axis in adults and fertilization rate of offspring were assessed. The results showed that treatment with E2 lead to increased number of feminization in zebrafish. In females, E2 decreased cumulative amount of spawning and inhibited the maturation of oocyte. In males, E2 inhibited the maturation and motility of sperm, as well as decreased the movement speed of sperm. These adverse effects on sperm might be responsible for the reduced fertilization observed in offspring. In addition, treatment with E2 changed the levels of steroid hormones in zebrafish gonad and altered the transcriptional levels of genes associated with HPG axis, which is responsible for the regulation of germ cells maturation and gonadal development in zebrafish. Overall, these results suggested that treatment with environmentally relevant concentrations of E2 for the full sexual maturity cycle resulted in adverse effects on reproduction in zebrafish.

Multidimensional Ultrasound Evaluation of Diastasis Recti Abdominis During Different Gestational Periods.

OBJECTIVE: The purpose of this study is to explore the application value of two-dimensional ultrasound and shear wave elastography (SWE) in the multidimensional evaluation of diastasis recti abdominis (DRA) during different gestational periods. METHODS: A cohort of 202 gravidas that were examined in our hospital between June 2021 and September 2022 were selected for the purpose of the study, which included 26 cases with <14 weeks of pregnancy, 36 cases in the 14th-27th week of pregnancy, 36 cases in the 28th-34th week of pregnancy, 32 cases in the 35th-38th week of pregnancy, 45 cases at 42 days postpartum, and 27 cases at 3 months postpartum. The inter-rectus distance (IRD) and the thickness in each gestational period were measured, and Young's modulus of the rectus abdominis at different gestational periods was measured using SWE by two sonographers. The differences in IRD, thickness, and elasticity characteristics during different periods, and the correlation between rectus abdominis elasticity and IRD, thickness, body mass index (BMI), neonatal weight, and delivery mode were analyzed and compared. The consistency of SWE parameters obtained by different sonographers was also compared. RESULTS: There were significant differences in IRD, thickness, and Young's modulus during different gestational periods (P = .000, P < .001, P < .001). Early postpartum IRD and Young's modulus did not restore to the level of early pregnancy (P < .001, P < .001), while the thickness of rectus abdominis was not significantly different from that of early pregnancy (P = .211). The Young's modulus of rectus abdominis was negatively correlated with the IRD (r = .515), positively correlated with the thickness of rectus abdominis (r = .408), and weakly negatively correlated with maternal BMI (r = -.296). There was no significant correlation with neonatal weight or delivery mode (P = .147, .648). The Bland-Altman plot showed that the two sonographers had good consistency in evaluating the elasticity of rectus abdominis by SWE. CONCLUSION: The multidimensional evaluation of DRA by ultrasound is feasible and IRD and Young's modulus can be used to evaluate the postpartum recovery of DRA. The combination of the two can objectively reflect the severity of DRA morphology and function.

Modeling and optimization study on degradation of organic contaminants using nZVI activated persulfate based on response surface methodology and artificial neural network: a case study of benzene as the model pollutant.

Due to the complicated transport and reactive behavior of organic contamination in groundwater, the development of mathematical models to aid field remediation planning and implementation attracts increasing attentions. In this study, the approach coupling response surface methodology (RSM), artificial neural networks (ANN), and kinetic models was implemented to model the degradation effects of nano-zero-valent iron (nZVI) activated persulfate (PS) systems on benzene, a common organic pollutant in groundwater. The proposed model was applied to optimize the process parameters in order to help predict the effects of multiple factors on benzene degradation rate. Meanwhile, the chemical oxidation kinetics was developed based on batch experiments under the optimized reaction conditions to predict the temporal degradation of benzene. The results indicated that benzene (0.25 mmol) would be theoretically completely oxidized in 1.45 mM PS with the PS/nZVI molar ratio of 4:1 at pH 3.9°C and 21.9 C. The RSM model predicted well the effects of the four factors on benzene degradation rate (R2 = 0.948), and the ANN with a hidden layer structure of [8-8] performed better compared to the RSM (R2 = 0.980). In addition, the involved benzene degradation systems fit well with the Type-2 and Type-3 pseudo-second order (PSO) kinetic models with R2 > 0.999. It suggested that the proposed statistical and kinetic-based modeling approach is promising support for predicting the chemical oxidation performance of organic contaminants in groundwater under the influence of multiple factors.

Predicting the effects of mutations on protein solubility using graph convolution network and protein language model representation.

Solubility is one of the most important properties of protein. Protein solubility can be greatly changed by single amino acid mutations and the reduced protein solubility could lead to diseases. Since experimental methods to determine solubility are time-consuming and expensive, in-silico methods have been developed to predict the protein solubility changes caused by mutations mostly through protein evolution information. However, these methods are slow since it takes long time to obtain evolution information through multiple sequence alignment. In addition, these methods are of low performance because they do not fully utilize protein 3D structures due to a lack of experimental structures for most proteins. Here, we proposed a sequence-based method DeepMutSol to predict solubility change from residual mutations based on the Graph Convolutional Neural Network (GCN), where the protein graph was initiated according to predicted protein structure from Alphafold2, and the nodes (residues) were represented by protein language embeddings. To circumvent the small data of solubility changes, we further pretrained the model over absolute protein solubility. DeepMutSol was shown to outperform state-of-the-art methods in benchmark tests. In addition, we applied the method to clinically relevant genes from the ClinVar database and the predicted solubility changes were shown able to separate pathogenic mutations. All of the data sets and the source code are available at https://github.com/biomed-AI/DeepMutSol.

Age-specific percentile-based prostate-specific antigen cutoff values predict the risk of prostate cancer: A single hospital observation.

Background: Testing for prostate-specific antigen (PSA) is often recommended for men with a potential risk of prostate cancer (PCa) before requiring advanced examination. However, the best PSA cutoff value remains controversial. Object: We compared the predictive performance of age-specific percentile-based PSA thresholds with a conventional cutoff of >4 ng/mL for the risk of PCa. Methods: We included men who received PSA measurements between 2003 and 2017 in a medical center in Taiwan. Logistic regression modeling was used to assess the association between age-specific percentile-based PSA thresholds and PCa risk in age subgroups. We further applied C-statistic and decision curve analysis to compare the predictive performance of age-specific percentile-based PSA with that of a conventional cutoff PSA. Results: We identified 626 patients with PCa and 40 836 patients without PCa. The slope of PSA in patients >60-year-old was almost 3 times that of those <60-year-old (0.713 vs 0.259). The risk effect sizes of the 75th percentile PSA cutoff (<60-year-old: 2.19; 60-70-year-old: 4.36; >70-year-old: 5.84 ng/mL) were comparable to those observed based on the conventional cutoff in all age groups. However, the discrimination performance of the 75th percentile PSA cutoff was better than that of the conventional cutoff among patients aged <60-year-old (C-statistic, 0.783 vs. 0.729, p < 0.05). The 75th percentile cutoffs also correctly identified an additional 2 patients with PCa for every 100 patients with PSA screening at the threshold probability of 20%. Conclusions: Our data support the use of the 75th percentile PSA cutoff to facilitate individualized risk assessment, particularly for patients aged <60-year-old.

Methanovulcanius yangii gen. nov., sp. nov., a hydrogenotrophic methanogen, isolated from a submarine mud volcano in the offshore area of southwestern Taiwan.

A novel mesophilic, hydrogenotrophic methanogen, strain CYW5T, was isolated from a sediment sample of a piston core collected from submarine mud volcano MV5 located in the offshore area of southwestern Taiwan. Cells of strain CYW5T were irregular coccids, 0.5-1.0 µm in diameter and lysed easily by 0.01 % sodium dodecyl sulphate (SDS) treatment. Strain CYW5Tutilized formate or hydrogen plus carbon dioxide as catabolic substrates for methanogenesis. The optimal growth conditions were 37 °C, 0.043-0.085 M NaCl and pH 6.02-7.32. The genomic DNA G+C content calculated from the genome sequence of strain CYW5T was 56.2 mol%. The results of phylogenetic analysis of 16S rRNA gene sequences indicated that strain CYW5T represented a member of the family Methanomicrobiaceae in the order Methanomicrobiales, and was closely related to the members of the genus Methanogenium. The most closely related species was Methanogenium cariaci JR1T (94.9 % of 16S rRNA gene sequence identity). The average nucleotide identity and average amino acid identity values between strain CYW5T and members of the family Methanomicrobiaceae were 74.7-78.5 % and 49.1-64.9%, respectively. Although many of the morphological and physiological characteristics of strain CYW5T and the species of the genus Methanogenium were similar, they were distinguishable by the differences in genomic G+C content and temperature, NaCl and pH ranges for growth. Based on these phenotypic, phylogenetic and genomic results, we propose that strain CYW5T represents a novel species, of a novel genus, named Methanovulcanius yangii gen. nov., sp. nov. The type strain is CYW5T (=BCRC AR10048T=DSM 100756T=NBRC 111404T).

Mucosa-associated microbiota dysbiosis in the terminal ileum correlates with bowel symptoms in diarrhea-predominant irritable bowel syndrome.

BACKGROUND AND AIMS: The mucosa-associated microbiota (MAM) is not as frequently studied in diarrhea-predominant irritable bowel syndrome (IBS-D) compared to the fecal microbiota. Here, we examined the MAM in the terminal ileum and its correlation with bowel symptoms in IBS-D. METHODS: Mucosal biopsies of the terminal ileum from 25 IBS-D patients and 25 healthy controls (HCs) were collected for 16S ribosomal RNA (rRNA) gene sequencing. Correlation analysis was performed. RESULTS: Compared to HCs, the MAM in the terminal ileum showed a decreased alpha-diversity in the IBS-D cohort (Chao1 and Shannon indexes, P < 0.05). And the overall MAM profile clustered separately in two groups (ADONIS, P < 0.05). At the phylum level, the relative abundance of Proteobacteria was significantly higher in the ileal MAM of patients with IBS-D while that of Firmicutes was significantly lower. At the genus level, the relative abundance of Pseudomonas was significantly higher in the IBS-D cohort, with lower Bacteroides and Ruminococcus. Moreover, 40.0% of IBS-D patients had multiple small nodules (nodular lymphoid hyperplasia, NLH) on the mucosal surface of the terminal ileum, which indicated a low-grade inflammation. In the IBS-D patients with NLH, the changes of Pseudomonas and Bacteroides were more overt. Correlation analysis revealed that the relative abundance of Pseudomonas positively correlated with abdominal pain and the severity of IBS. CONCLUSION: IBS-D patients showed a dysbiosis of MAM in the terminal ileum, which may be associated with bowel symptoms. Moreover, 40.0% of them displayed mucosal low-grade inflammation, with a more severe mucosal microbial disturbance.

Efficacy and safety of anti-programmed cell death protein 1 antibody combination therapy in patients with advanced experienced epidermal growth factor receptor-tyrosine kinase inhibitor-resistant lung adenocarcinoma: a retrospective cohort study.

Background: The effectiveness of combining anti-programmed cell death protein 1 (PD-1) and chemotherapy has been evaluated as superior to that of chemotherapy alone in the patients with advanced epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-resistant non-small cell lung cancer (NSCLC). In this study the efficacy and safety of anti-PD-1 combination therapy were evaluated retrospectively in patients who experienced EGFR-TKI-resistant with advanced lung adenocarcinoma (LUAD), with the goal of providing helpful guidance for clinical application. Methods: The clinical results of patients with incurable LUAD who received anti-PD-1 antibody combined with or without anti-angiogenic or chemotherapy after EGFR-TKI therapy failure were collected. The efficacy was calculated based on the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). The efficacy of the regimes was compared according to treatment groups and programmed cell death ligand 1 (PD-L1) expression. Results: The final analysis included a total of 43 patients with advanced EGFR-mutant LUAD. The overall cohort had an ORR of 23.3%, median PFS (mPFS) of 6.5 months, and median OS (mOS) of 10.6 months. No notable distinction was observed in mPFS and mOS among patients receiving three types of anti-PD-1 antibody combination therapies. Patients with positive PD-L1 expression showed a longer mPFS compared to patients with negative PD-L1 expression. No statistical difference was detected in terms of mPFS between the use of immune combination chemotherapy and immune combination anti-angiogenic therapy in the PD-L1 positive subgroup, and PFS was prolonged regardless of the PD-L1 expression status being positive or negative in the population receiving immune combination chemotherapy. Treatment-related adverse events (TRAEs) of grade 3 or higher were observed in 16.3% of patients, including chemotherapy-containing immunotherapy. No deaths resulting from immune-related adverse events (irAEs) were reported, and only 1 patient receiving immunotherapy plus chemotherapy had to discontinue treatment due to irAEs. Conclusions: Combination immunotherapy is feasible in post-TKI resistant individuals with LUAD harboring EGFR mutations. Immune combination chemotherapy and immune combination anti-angiogenic therapy have equivalent efficacy in the PD-L1 positive population. PD-L1 expression can be used as a reference for screening candidates for combination immunotherapy.

Echinacoside exerts neuroprotection via suppressing microglial α-synuclein/TLR2/NF-κB/NLRP3 axis in parkinsonian models.

BACKGROUND: Echinacoside (ECH), a natural active compound, was found to exert neuroprotection in Parkinson's disease (PD). However, the underlying molecular mechanisms remain controversial. PURPOSE: This study aimed to explore the roles of ECH in PD and its engaged mechanisms. CONCLUSION: In vivo, MPTP was adapted to construct subacute PD mouse model to explore the regulation of ECH on NLRP3 inflammasome. In vitro, α-synuclein (α-syn)/MPP+ was used to mediate the activation of NLRP3 inflammasome in BV2 cells, and the mechanism of ECH regulation of it was explored with molecular docking, immunofluorescence, Western blotting, and small molecule inhibitors. CONCLUSION: The activation of microglial NLRP3 inflammasome could be evoked by MPTP in vitro, but its toxic metabolite MPP+ alone cannot trigger the activation of NLRP3 inflammasome in vitro, which requires α-synuclein (α-syn) priming. Exogenous α-syn could evoke microglial TLR2/NF-κB/NLRP3 axis, playing the priming role in MPP+ -mediated NLRP3 inflammasome activation. ECH can suppress the upregulation of α-syn in MPTP-treated mice and BV2 microglia. It can also suppress the activation of the TLR2/NF-κB/NLRP3 axis induced by α-syn. CONCLUSION: ECH exerts neuroprotective effects by downregulating the TLR2/NF-κB/NLRP3 axis via reducing the expression of α-syn in the PD models.

Anatomic mapping of acral melanocytic nevi and acral lentiginous melanomas among Taiwanese patients: A retrospective cohort study.

BACKGROUND: The early diagnosis of acral lentiginous melanoma (ALM) contributes to clinical outcomes since ALM can be mistaken for acral melanocytic nevus (AMN). ALM occurrence is reported to correlate with stress-bearing areas, which may assist in differential diagnoses. Our objective is to evaluate the distribution patterns of ALMs and AMNs on the palms and soles among Taiwanese patients. METHODS: A retrospective analysis was performed by reviewing the charts of 1400 patients diagnosed with benign and malignant pigmented lesions confirmed after excisional biopsy at our institution between 2000 and 2022 in Taiwan. Correlations between lesions and clinicopathological factors were analyzed. RESULTS: 309 AMNs and 177 ALMs were included. Mechanical stress was significantly associated with plantar ALMs (weight-bearing area: 92.65 %, arch: 7.35 %, P < 0.001). Significant differences in the distribution patterns were observed for plantar ALMs compared with all AMNs (P < 0.001) and non-atypical AMNs (P < 0.001), but were not observed between palmar AMNs and ALMs. CONCLUSION: Plantar ALMs were most commonly observed on the weight-bearing areas of the soles, distinct from the distribution of all AMNs and of non-atypical AMNs. The distribution features and anatomic mapping of ALMs may facilitate the early clinical diagnosis of ALM.

Cognition & Educational Achievement in the Toronto Adolescent and Youth (TAY) Cohort Study: Rationale, Methods, and Early Data.

BACKGROUND: Cognition and educational achievement in youth are both linked to psychosis risk. One major aim of the Toronto Adolescent and Youth (TAY) Cohort study is to characterize how cognitive and educational achievement trajectories inform the course of psychosis spectrum symptoms (PSS), functioning, and suicidality. Here, we describe the protocol for the cognitive and educational data, and early baseline data. METHODS: Cognitive assessment design is aligned with youth population cohort studies, including the NIH Toolbox, Rey Auditory Verbal Learning Test, Wechsler Matrix Reasoning Task, and Little Man Task. Participants complete an educational achievement questionnaire and report cards are requested. Completion rates, descriptive data, and differences across PSS status are reported in the first participants (N=417) aged 11-24 years, recruited between May 4, 2021 and February 2, 2023. RESULTS: 83.7% of the sample completed cognitive testing, 88.2% completed the educational questionnaire, whereas report cards were collected for 40.3%. Modifications to workflows were implemented to improve data collection. Participants meeting criteria for PSS demonstrated lower performance on numerous key cognitive indices compared with those who did not (p<0.05), and also had more academic/educational problems. CONCLUSIONS: Following youth longitudinally will enable trajectory mapping and prediction based on cognitive and educational performance in relation to PSS in treatment-seeking youth. Youth with PSS had lower cognitive performance and worse educational outcomes compared to youth without PSS. Results show the feasibility of collecting cognitive and educational outcomes in a cohort of youth seeking treatment related to mental illness and substance use.

Decoupling tourism growth from carbon emissions: Evidence from Chengdu, China.

The fast growth increases in energy use and greenhouse gas emissions in China's tourism industry. This article assessed the carbon emissions of tourist Chengdu's traffic patterns and how they are expected to change between 2005 and 2021 and explains why tourism carbon decoupling is important for sustainable tourism development. In order to investigate how carbon emissions from tourism may expand without necessarily increasing in tandem with GDP and the variables that influence it, the Tapir model and the LMDI (logarithmic mean Divisia index) method were used. In our study, we looked at six important variables, including (1) the number of visitors, (2) the level of tourism spending per capita, (3) the contribution rate of the tourism sector with according to the country's total national income, (4) the amount of passenger traffic relative to GDP, and (5) the energy consumption relative to the volume of passenger traffic. There have been five stages in the correlation: positively charged decoupling, weak decoupling, negative decoupling, strong coupling, and strong decoupling. All of these describe the relationship between the expansion of China's tourist industry and the country's carbon emissions. Findings highlighted the importance of large numbers of visitors, high levels of per-person tourism spending, and low passenger traffic volume per unit of energy consumption as key positive factors. The rise of carbon emissions may also be slowed by increasing the number of passengers transported per unit of GDP. Carbon emissions from tourists in Chengdu are fluctuating, and this influences the city's economy. The findings have significant theoretical and practical implications for Chengdu's transition to a low-carbon economy and for the formulation of policies to reduce emissions. During the research period, most Chinese provinces exhibited ideal decoupling situations. This research has the potential to be used as a scientific resource for guiding the long-term growth as a result of China's tourist sector.

One-Step Method for Fabricating Janus Aramid Nanofiber/MXene Nanocomposite Films with Improved Joule Heating and Thermal Camouflage Properties.

The integration of ultraflexible and mechanically robust films with electric heaters and camouflage technology provides a promising platform for the development of wearable devices, especially for aerospace and military applications. Herein, we present a facile and efficient one-step vacuum-assisted filtration method for fabricating Janus films based on aramid nanofibers (ANF) and Ti3C2Tx (MXene). The ANF/MXene nanocomposite film exhibits remarkable properties, including high conductivity (23809.5 S/m), excellent mechanical strength (102.54 MPa), and outstanding thermal stability (575 °C). Most notably, the Janus ANF/MXene composite film demonstrates superior Joule heating performance with a low driving voltage (1-5 V), high heating temperature (30-276 °C), and rapid response time (within 5 s). Additionally, the film exhibits effective thermal camouflage (72 °C for objects with temperatures above 163 °C) and excellent electromagnetic interference shielding properties (SSE/t = 32475.6 dB cm2/g). These results demonstrate that Janus ANF/MXene films possess a unique combination of thermal camouflage, Joule heating, and electromagnetic interference shielding properties, making them highly promising for wearable devices, high-performance electrical heating, infrared stealth, and security protection applications.

Integration of risk variants from GWAS with SARS-CoV-2 RNA interactome prioritizes FUBP1 and RAB2A as risk genes for COVID-19.

The role of host genetic factors in COVID-19 outcomes remains unclear despite various genome-wide association studies (GWAS). We annotate all significant variants and those variants in high LD (R2 > 0.8) from the COVID-19 host genetics initiative (HGI) and identify risk genes by recognizing genes intolerant nonsynonymous mutations in coding regions and genes associated with cis-expression quantitative trait loci (cis-eQTL) in non-coding regions. These genes are enriched in the immune response pathway and viral life cycle. It has been found that host RNA binding proteins (RBPs) participate in different phases of the SARS-CoV-2 life cycle. We collect 503 RBPs that interact with SARS-CoV-2 RNA concluded from in vitro studies. Combining risk genes from the HGI with RBPs, we identify two COVID-19 risk loci that regulate the expression levels of FUBP1 and RAB2A in the lung. Due to the risk allele, COVID-19 patients show downregulation of FUBP1 and upregulation of RAB2A. Using single-cell RNA sequencing data, we show that FUBP1 and RAB2A are expressed in SARS-CoV-2-infected upper respiratory tract epithelial cells. We further identify NC_000001.11:g.77984833C>A and NC_000008.11:g.60559280T>C as functional variants by surveying allele-specific transcription factor sites and cis-regulatory elements and performing motif analysis. To sum up, our research, which associates human genetics with expression levels of RBPs, identifies FUBP1 and RAB2A as two risk genes for COVID-19 and reveals the anti-viral role of FUBP1 and the pro-viral role of RAB2A in the infection of SARS-CoV-2.