Association of serum 25-hydroxyvitamin D concentrations with all-cause and cause-specific mortality among individuals with gout and hyperuricemia.

BACKGROUND: We aimed to probe the association of serum 25-hydroxyvitamin D [25(OH)D] concentrations with all-cause and cause-specific mortality among patients with gout and hyperuricemia (HUA). METHODS: The study included 1169 gout patients and 7029 HUA patients from the National Health and Nutrition Examination Survey (NHANES) 2007-2018 and 2001-2018, respectively. The association between serum 25(OH)D and mortality was evaluated by Cox proportional hazard and restricted cubic spline models. RESULTS: Among participants with gout and HUA, the weighted mean concentrations of serum 25(OH)D were 71.49 ± 30.09 nmol/L and 64.81 ± 26.92 nmol/L, respectively. Vitamin D deficiency occurred in 29.68% of gout patients and 37.83% of HUA patients. During 6783 person-years of follow-up among gout patients, 248 all-cause deaths occurred, among which 76 died from cardiovascular disease (CVD) and 49 died from cancer. 1375 HUA patients were recorded for all-cause mortality during 59,859 person-years of follow-up, including 427 CVD deaths and 232 cancer deaths. After multifactorial adjustment, per one-unit increment in natural log-transformed 25(OH)D was associated with lower risk of 55% all-cause mortality and 61% CVD mortality among gout patients, and a 45% reduced risk of cancer mortality among HUA patients. Restricted cubic splines showed a U-shaped relationship with all-cause and CVD mortality among HUA patients, with inflection points of 72.7 nmol/L and 38.0 nmol/L, respectively. The results were robust in subgroup and sensitivity analyses. CONCLUSIONS: Serum 25(OH)D was negatively linearly correlated with mortality among gout patients, whereas U-shaped correlated with mortality in HUA patients. These results indicate that adequate vitamin D status could prevent premature death.

Mitochondrial DNA Leakage Promotes Persistent Pancreatic Acinar Cell Injury in Acute Pancreatitis via the cGAS-STING-NF-κB Pathway.

Previous research has shown that the activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway in macrophages can promote severe acute pancreatitis through the release of inflammatory factors. The role of this pathway in pancreatic acinar cells, however, has not been studied, and understanding its mechanism could be crucial. We analysed plasma from 50 acute pancreatitis (AP) patients and 10 healthy donors using digital PCR, which links mitochondrial DNA (mtDNA) levels to the severity of AP. Single-cell sequencing of the pancreas during AP revealed differentially expressed genes and pathways in acinar cells. Experimental studies using mouse and cell models, which included mtDNA staining and quantitative PCR, revealed mtDNA leakage and the activation of STING-related pathways, indicating potential inflammatory mechanisms in AP. In conclusion, our study revealed that the mtDNA-STING-nuclear factor κB(NF-κB) pathway in pancreatic acinar cells could be a novel pathogenic factor in AP.

Development of a Quick and Highly Sensitive Amplified Luminescent Proximity Homogeneous Assay for Detection of Saxitoxin in Shellfish.

Saxitoxin (STX), an exceptionally potent marine toxin for which no antidote is currently available, is produced by methanogens and cyanobacteria. This poses a significant threat to both shellfish aquaculture and human health. Consequently, the development of a rapid, highly sensitive STX detection method is of great significance. The objective of this research is to create a novel approach for identifying STX. Therefore, amplified luminescent proximity homogeneous assay (AlphaLISA) was established using a direct competition method based on the principles of fluorescence resonance energy transfer and antigen-antibody specific binding. This method is sensitive, rapid, performed without washing, easy to operate, and can detect 8-128 ng/mL of STX in only 10 min. The limit of detection achieved by this method is as low as 4.29 ng/mL with coefficients of variation for the intra-batch and inter-batch analyses ranging from 2.61% to 3.63% and from 7.67% to 8.30%, respectively. In conclusion, our study successfully establishes a simple yet sensitive, rapid, and accurate AlphaLISA method for the detection of STX which holds great potential in advancing research on marine biotoxins.

Low-Cost Indoor Sensor Deployment for Predicting PM2.5 Exposure.

Indoor air quality is critical to human health, as individuals spend an average of 90% of their time indoors. However, indoor particulate matter (PM) sensor networks are not deployed as often as outdoor sensor networks. In this study, indoor PM2.5 exposure is investigated via 2 low-cost sensor networks in Pittsburgh. The concentrations reported by the networks were fed into a Monte Carlo simulation to predict daily PM2.5 exposure for 4 demographics (indoor workers, outdoor workers, schoolchildren, and retirees). Additionally, this study compares the effects of 4 different correction factors on reported concentrations from the PurpleAir sensors, including both empirical and physics-based corrections. The results of the Monte Carlo simulation show that mean PM2.5 exposure varied by 1.5 µg/m3 or less when indoor and outdoor concentrations were similar. When indoor PM concentrations were lower than outdoor, increasing the time spent outdoors on the simulation increased exposure by up to 3 µg/m3. These differences in exposure highlight the importance of carefully selecting sites for sensor deployment and show the value of having a robust low-cost sensor network with both indoor and outdoor sensor placement.

Construction and validation of a nomogram for predicting the prognosis of breast cancer patients who received adjuvant therapy: an analysis based on the SEER database.

Background: Breast cancer is the most common malignant tumor in women globally. Despite advances in primary treatment, the role of adjuvant therapy in reducing recurrence and improving survival is critical; however, there is a notable lack of tailored prognostic models for patients receiving adjuvant therapy. This study used the Surveillance, Epidemiology, and End Results (SEER) database to develop a prognostic nomogram for breast cancer patients receiving adjuvant therapy. Methods: The data of breast cancer patients who received adjuvant therapy after surgery in 2014-2015 were extracted from the SEER database. Univariate Cox regression identified significant prognostic variables that were further refined by least absolute shrinkage and selection operator (LASSO) regression and cross-validation analyses. These variables were incorporated into a multivariate Cox regression analysis to establish the predictive model. This model was visualized and validated using various statistical measures. Results: A total of 54,960 patients were included in the study, with 38,472 in the training set and 16,488 in the validation set. Age, sex, race, marital status, grade, tumor (T) stage, lymph node (N) stage, subtype, and radiotherapy were found to be significant independent risk factors of 1-, 3-, and 5-year overall survival (OS). The receiver operating characteristic curve area for 1-, 3-, and 5-year OS was >0.76 in both sets. The consistency index values were 0.768 and 0.763 for the training and validation sets, respectively. The calibration curves showed good fit, and the nomogram exhibited substantial clinical utility. Conclusions: Incorporating various significant factors, the constructed nomogram was able to effectively predict the prognosis of breast cancer patients who received adjuvant therapy. This nomogram extends understandings of complex prognosis scenarios. In addition, it could enhance personalized treatment plans and assist in patient counseling.

A Comprehensive Investigation of Dietary Micronutrient Intakes and Risk of Alcoholic Liver Disease.

BACKGROUND: The investigation of dietary micronutrient intakes and risk of alcoholic liver disease (ALD) based on observational studies was limited. OBJECTIVES: Our study aimed to explore the associations of 30 dietary micronutrients intakes with risk of ALD, interactions between dietary micronutrients and genetic variation, and mediation effects of blood and urinary biomarkers on the associations between dietary micronutrients and risk of ALD. METHODS: A case-control study was conducted within the UK Biobank cohort, with 231 incident ALD cases and 1386 controls. Dietary data were collected using a dietary questionnaire that relied on a 24-h dietary recall of the previous day. Logistic regression models were employed to assess the associations of dietary micronutrient intakes with risk of ALD. We conducted stratified analyses on the associations between dietary micronutrient intakes and risk of ALD by PNPLA3 rs738409 and tested the interactions between dietary micronutrients and genetic variation. In addition, we conducted mediation analyses to investigate the mediating effects of biomarkers on the associations between dietary micronutrients and risk of ALD. RESULTS: Our findings indicated significant inverse associations of thiamin, riboflavin, niacin equivalent, pantothenic acid, vitamin B-6, folate, vitamin E, calcium, magnesium, phosphorus, potassium, copper, iodine, and manganese with risk of ALD (all false discovery rate-Ptrend < 0.050). We also found a significant interaction between PNPLA3 rs738409 and magnesium (Pinteraction = 0.028). Creatinine (enzymatic) in urine, aspartate aminotransferase, and insulin-like growth factor 1 were the top 3 biomarkers with the highest number of significant mediation effects on the associations between the dietary micronutrients and risk of ALD. CONCLUSIONS: Dietary intakes of thiamin, riboflavin, niacin equivalent, pantothenic acid, vitamin B-6, folate, vitamin E, calcium, magnesium, phosphorus, potassium, copper, iodine, and manganese were inversely associated with risk of ALD.

Harnessing co-evolutionary interactions between plants and Streptomyces to combat drought stress.

Streptomyces is a drought-tolerant bacterial genus in soils, which forms close associations with plants to provide host resilience to drought stress. Here we synthesize the emerging research that illuminates the multifaceted interactions of Streptomyces spp. in both plant and soil environments. It also explores the potential co-evolutionary relationship between plants and Streptomyces spp. to forge mutualistic relationships, providing drought tolerance to plants. We propose that further advancement in fundamental knowledge of eco-evolutionary interactions between plants and Streptomyces spp. is crucial and holds substantial promise for developing effective strategies to combat drought stress, ensuring sustainable agriculture and environmental sustainability in the face of climate change.

Salinity-induced variations in bacterial composition and co-occurrence patterns within Salicornia-based constructed wetlands in mariculture.

Constructed wetlands use vegetation and microorganisms to remove contaminants like nitrogen and phosphorus from water. For mariculture, the impact of salinity on the efficiency of wastewater treatment of wetlands is unneglectable. However, little is known about their impact on the microbiome in constructed wetlands. Here, we set four salinity levels (15, 22, 29, and 36) in Salicornia constructed wetlands, and the experiment was conducted for a period of 72 days. The 15 group exhibited the highest removal rates of nitrogen compounds and phosphate, compared to the other salinity groups, the nosZ gene exhibited significantly higher expression in the 22 group (p < 0.05), indicated that microorganisms in 22 salinity have higher denitrification abilities. The three dominant phyla identified within the microbiomes were Proteobacteria, known for their diverse metabolic capabilities; Cyanobacteria, important for photosynthesis and nitrogen fixation; and Firmicutes, which include many fermenters. The ecological network analysis revealed a 'small world' model, characterized by high interconnectivity and short path lengths between microbial species, and had higher co-occurrence (45.13%) observed in this study comparing to the Erdös-Réyni random one (32.35%). The genus Microbulbifer emerged as the sole connector taxon, pivotal for integrating different microbial communities involved in nitrogen removal. A negative correlation was observed between salinity levels and network complexity, as assessed by the number of connections and diversity of interactions within the microbial community. Collectively, these findings underscore the critical role of microbial community interactions in optimizing nitrogen removal in constructed wetlands, with potential applications in the design and management of such systems for improved wastewater treatment in mariculture.

Group Theory on Quasisymmetry and Protected Near Degeneracy.

In solid state systems, group representation theory is powerful in characterizing the behavior of quasiparticles, notably the energy degeneracy. While conventional group theory is effective in answering yes-or-no questions related to symmetry breaking, its application to determining the magnitude of energy splitting resulting from symmetry lowering is limited. Here, we propose a theory on quasisymmetry and near degeneracy, thereby expanding the applicability of group theory to address questions regarding large-or-small energy splitting. Defined within the degenerate subspace of an unperturbed Hamiltonian, quasisymmetries form an enlarged symmetry group eliminating the first-order splitting. This framework ensures that the magnitude of splitting arises as a second-order effect of symmetry-lowering perturbations, such as external fields and spin-orbit coupling. We systematically tabulate the quasisymmetry groups within 32 crystallographic point groups and find all the possible unitary quasisymmetry group structures regarding double degeneracy. Applying our theory to the realistic material AgLa, we predict a "quasi-Dirac semimetal" phase characterized by two tiny-gap band anticrossings.

The cultivable gut bacteria Enterococcus mundtii promotes early-instar larval growth of Conogethes punctiferalis via enhancing digestive enzyme activity.

BACKGROUND: Gut bacteria are crucial in influencing insect development and even phenotypic plasticity. The yellow peach moth Conogethes punctiferalis, as a significant borer pest, has been the subject of limited reports regarding the structural and diversification changes in its gut microbiota during feeding, and their potential impacts on the growth and development of the host insects. RESULTS: This study, employing 16S rRNA sequencing, demonstrates distinct shifts in the larvae gut microbiome of C. punctiferalis between different feeding stages, highlighting a pronounced diversity in the early-instar with Enterococcus as a predominant genus in laboratory populations. Through in vitro cultivation and sequencing, three bacterial strains - Micrococcus sp., Brevibacterium sp. and Enterococcus mundtii - were isolated and characterized. Bioassays revealed that E. mundtii-infused corn significantly boosts early-instar larval growth, enhancing both body length and weight. Quantitative PCR and spectrophotometry confirmed a higher abundance of E. mundtii in younger larvae, correlating with increased digestive enzyme activity and total protein levels. CONCLUSION: This study reveals the heightened gut microbiota diversity in early instars of C. punctiferalis larvae, highlighting that Enterococcus represent a predominant bacteria in laboratory populations. In vitro cultivation and bioassays unequivocally demonstrate the significant role of the cultivable gut bacteria E. mundtii in promoting the growth of early-instar larva. These findings provide a solid theoretical foundation for advancing the comprehension of the intricate interactions between gut microbiota and insect hosts, as well as for the development of eco-friendly pest control technologies based on targeted manipulation of insect gut microbial communities. © 2024 Society of Chemical Industry.

Process Optimization and Quality Components Analysis of γ-Aminobutyric Acid Pickled Tea.

Pickled tea is an anaerobically fermented tea common in Thailand, Myanmar and Yunnan minority areas. γ-aminobutyric acid (GABA) is non-protein amino acid with multiple bioactives, which can be easily produced under anaerobic conditions. During the processing of pickled tea, controlling the process parameters is effective for the production of GABA-rich products; however, the precise parameters remain to be clarified. In the present study, the fresh leaves of Camellia sinensis (L.) Kuntze (C. sinensis) 'FudingDabai', C. sinensis 'MabianLv No. 1', C. sinensis 'Wuniuzao' and C. sinensis 'Fuxuan No. 9' were used as raw materials to process GABA-rich pickled tea. Single-factor and orthogonal experiments were conducted to determine the best tea cultivars and optimize the best processing parameters via comparing the content of GABA, tea polyphenols (TPs) and other biochemical components of GABA-rich pickled tea. The results of the signal-factor experiment showed that the fresh leaves of C. sinensis 'MabianLv No. 1' had the highest GABA content of 2.61 mg·g-1 after treatment with vacuum for 6 h; therefore, C. sinensis 'MabianLv No. 1' was selected as the raw material for the subsequent experiments. Orthogonal experiments showed that the highest GABA content of 2.53 mg·g-1 was found in the pickled tea with 8 h of vacuum treatment, 20 min of rolling after microwave fixing, 20 min of spreading and 20 d of anaerobic fermentation at room temperature. Further, the sensory evaluation showed that it possesses a strong sour taste with a slight sweetness and a light yellow color and better comprehensive quality. This indicates that these parameters are optimal for the processing of GABA-rich pickled tea. This study will provide scientific basis for the subsequent production of high GABA tea.

Design, Synthesis and Evaluation of A Novel Teoptinib Derivative as an Effective Anti-Hepatocellular Carcinoma Agent.

BACKGROUND & PURPOSE: Hepatocellular Carcinoma (HCC) is a type of liver cancer known for its poor prognosis and high mortality. Teoptinib is a highly selective MET inhibitor that has been used in the treatment of liver cancer. Although good progress has been made in clinical treatment, further improvement is still needed. In this study, a series of novel Teoptinib derivatives were synthesized and evaluated as anti-cancer agents for the treatment of liver cancer, and an oral nanodrug delivery system was also explored. METHODS: A series of novel Teoptinib derivatives were synthesized, and an oral nanodrug delivery system was also explored. HPLC, high-resolution mass spectrometer and NMR were used to determine the structure and molecular formula of the synthesized compounds. Zeta potential assay was used to access the particle size distribution and zeta potential of the nanoparticles. MTT assay, cell colony formation assay, cell apoptosis inhibition assay, cell scratch assay, and the MHCC-97H xenograft model of nude mice assay were used to evaluate the in vitro and in vivo anti-tumor activity of the synthesized compounds. RESULTS: Compound (R)-10 showed the best antitumor activity with 0.010 µM of the IC50 value against MHCC-97H, a human liver cancer cell line with high c-Met expression. The MHCC-97H xenograft model of nude mice assay showed that nano-prodrug of compound (R)-10 exhibited good in vivo activity with 87.67% of the TGI at the dosage of 8 mg/kg. CONCLUSION: We designed and synthesized a series of c-Met inhibitors containing different side chains and chiral centers as anti-liver cancer agents. Among them, compound (R)-10 shows a promising effect as a lead molecule for further study in the treatment of liver cancer. The successful incorporation of (R)-10 into a novel oral nanodrug delivery system highlights the importance of effective drug delivery systems for enhanced therapeutic efficacy.

Carrimycin inhibits coronavirus replication by decreasing the efficiency of programmed -1 ribosomal frameshifting through directly binding to the RNA pseudoknot of viral frameshift-stimulatory element.

The pandemic of SARS-CoV-2 worldwide with successive emerging variants urgently calls for small-molecule oral drugs with broad-spectrum antiviral activity. Here, we show that carrimycin, a new macrolide antibiotic in the clinic and an antiviral candidate for SARS-CoV-2 in phase III trials, decreases the efficiency of programmed -1 ribosomal frameshifting of coronaviruses and thus impedes viral replication in a broad-spectrum fashion. Carrimycin binds directly to the coronaviral frameshift-stimulatory element (FSE) RNA pseudoknot, interrupting the viral protein translation switch from ORF1a to ORF1b and thereby reducing the level of the core components of the viral replication and transcription complexes. Combined carrimycin with known viral replicase inhibitors yielded a synergistic inhibitory effect on coronaviruses. Because the FSE mechanism is essential in all coronaviruses, carrimycin could be a new broad-spectrum antiviral drug for human coronaviruses by directly targeting the conserved coronaviral FSE RNA. This finding may open a new direction in antiviral drug discovery for coronavirus variants.

High-level reverse intersystem crossing of charge transfer compounds: to fluoresce or not to fluoresce?

Thermally activated delayed fluorescence (TADF) has been widely applied to electroluminescent materials to take the best advantage of triplet excitons. For some materials, the TADF originates from high-level reverse intersystem crossing (hRISC), and has attracted much attention due to its high efficiency for utilizing the triplet excitons. However, reports concerning the mechanistic studies on the hRISC-TADF process and structure-property correlation are sparse. In this study, we prepared three compounds containing triphenylamine and benzophenone with different substitution positions, o-TPA-BP, m-TPA-BP, and p-TPA-BP, in which only p-TPA-BP displays strong luminescence and hRISC-TADF features. To investigate the mechanism of the substituent-position-dependent hRISC-TADF, ultrafast time-resolved spectroscopy was utilized to observe the deactivation pathways with the assistance of theoretical calculations. The results show that o-TPA-BP will not generate triplet species, and the triplet species for m-TPA-BP will rapidly deactivate. Only p-TPA-BP can transition back to the singlet state from the T2 state effectively and exhibit a large gap between T1 and T2 to favor the hRISC route. These results illustrate how the substitution position affects the ISC and further influences the luminescence properties, which can provide new insights for developing new high-efficiency luminescent materials.

Mesoporous CdO/CdGa2O4 microsphere for rapidly detecting triethylamine at ppb level.

Developing fast, accurate and sensitive triethylamine gas sensors with low detection limits is paramount to ensure the safety of workers and the public. However, sensors based on single metal oxide materials still suffer from drawbacks such as low response sensitivity and long response and recovery times. To address these challenges, in this work, a series of mesoporous CdO/CdGa2O4 microspheres were synthesized. We optimized the sensor's sensing performance to triethylamine by fine-tuning the ratio of CdO to CdGa2O4. Among them, CdO:3CdGa2O4-based sensor demonstrates a rapid response time of 2 s to detect 100 ppm of triethylamine, with a high response value of 211 and exceptional selectivity. Furthermore, it exhibits a low detection limit of 20 ppb for triethylamine, making it suitable for practically testing fish freshness. Crucially, electron transfer between the heterojunctions increases the chemically adsorbed oxygen on the materials' surface, thereby enhancing the sensor's response sensitivity to triethylamine. This discovery provides new insights and methodologies for the design of highly efficient triethylamine gas sensors.

Enhanced oxygen anions generation on Bi2S3/Sb2S3 heterostructure by visible light for trace H2S detection at room temperature.

Bismuth sulfide (Bi2S3) possesses unique properties that make it a promising material for effective hydrogen sulfide (H2S) detection at room temperature. However, when exposed to light, the oxygen anions (O2-(ads)) adsorbed on the surface of Bi2S3 can react with photoinduced holes, ultimately reducing the ability to respond to H2S. In this study, Bi2S3/Sb2S3 heterostructures were synthesized, producing photoinduced oxygen anions (O2-(hv)) under visible light conditions, resulting in enhanced H2S sensing capability. The Bi2S3/Sb2S3 heterostructure sensor exhibits a two-fold increase in sensing response to 500 ppb H2S under in door light conditions relative to its performance in darkness. Additionally, the sensing response of the Bi2S3/Sb2S3 sensor (Ra/Rg= 23.3) was approximately five times higher than pure Bi2S3. The improved sensing performance of the Bi2S3/Sb2S3 heterostructures is attributable to the synergistic influence of the heterostructure configuration and light modulation, which enhances the H2S sensing performance by facilitating rapid charge transfer and increasing active sites (O2-(hv)) when exposed to visible light.

Potential role of blood pressure variability and plasma neurofilament light in the mechanism of comorbidity between Alzheimer's disease and cerebral small vessel disease.

INTRODUCTION: Long-term blood pressure variability (BPV) and plasma neurofilament light (pNfL) have been identified as potential biomarkers for Alzheimer's disease (AD) and cerebral small vessel disease (CSVD). However, the relationship between BPV, pNfL, and their association with the comorbidity of AD and CSVD remains unknown. METHODS: Participants with normal cognition and mild cognitive impairment from the Alzheimer's Disease Neuroimaging Initiative study were included in the data analysis. Linear mixed-effects regression models and causal mediation analyses were conducted to investigate the relationship among BPV, pNfL, comorbidity-related brain structural changes (hippocampal atrophy and white matter hyperintensities [WMH]), and cognitive function. RESULTS: BPV was associated with pNfL, volumes of hippocampus and WMH, and cognition. pNfL mediated the effects of BPV on brain structural changes and cognition. DISCUSSION: Our findings suggest a potential role of BPV and pNfL in the mechanism of comorbidity between AD and CSVD, underscoring the importance of BPV intervention in the general population. HIGHLIGHTS: Individuals with both Alzheimer's disease (AD) and cerebral small vessel disease (CSVD) pathologies had elevated blood pressure variability (BPV) and plasma neurofilament light (pNfL). The association between different components of BPV and brain structural changes may vary. BPV was associated with pNfL levels independent of average blood pressure. pNfL mediated the effects of BPV on comorbidity-related brain structural changes and cognitive performance.

Exposure to polycyclic aromatic hydrocarbons (PAHs) from domestic heating and cooking combustion of different fuel types for elders in rural China.

Solid fuel combustion emitted abundant pollutants, especially polycyclic aromatic hydrocarbons (PAHs) which had significant minus impact on human health in rural China. PAHs in PM2.5 emitted from different fuels combustion and hydroxylated metabolites of PAHs (OH-PAHs) in urine samples of different fuel users were detected in this study. The indoor PAHs were higher than that in outdoors for solid fuel use households, and the concentration of PAHs in the indoor of liquefied petroleum gas (LPG) use household was not much lower than solid fuel use households. Biogas-use household produced the lowest PAHs, which significantly reduced 64-82% compared with those emitted by solid fuel combustion. The different combustion conditions influenced the gaseous PAHs in indoors between two sampling sites. The gas/particle partition indicated that PAHs tended to occur in the particle phase with increased molecular weight, and the absorption was the main mechanism. The relative higher contribution of high molecular weight PAHs (HMW-PAHs) in solid fuel use households than in clean fuel use households, induced more health risks of PAHs. The concentration of Σ10OH-PAHs in the urine samples for elders of different fuel-use households displayed the trend of coal (83.27 ng/mL) > wood (79.32 ng/mL) > LPG (51.61 ng/mL) > biogas (28.96 ng/mL), and OH-NaPs was the predominant metabolites, which accounted for more than 90% of the total concentration. The carcinogenic risk of PAHs based on internal exposure was greater than or close to 10-4, with serious carcinogenic risks. This was different with the incremental lifetime cancer risk based on the atmospheric concentrations. The exposure of PAHs from solid fuel combustion for human being especially for the elders in this region should be concerned, and more data should be done for the internal exposure of PAHs.

Dysfunction of Complementarity Determining Region 1 Encoded by T Cell Receptor Beta Variable Gene Is Potentially Associated with African Swine Fever Virus Infection in Pigs.

The beta T-cell receptor (TRB) expressed by beta T cells is essential for foreign antigen recognition. The TRB locus contains a TRBV family that encodes three complementarity determining regions (CDRs). CDR1 is associated with antigen recognition and interactions with MHC molecules. In contrast to domestic pigs, African suids lack a 284-bp segment spanning exons 1 and 2 of the TRBV27 gene that contains a sequence encoding CDR1. In this study, we used the African swine fever virus (ASFV) as an example to investigate the effect of deleting the TRBV27-encoded CDR1 on the resistance of domestic pigs to exotic pathogens. We first successfully generated TRBV27-edited fibroblasts with disruption of the CDR1 sequence using CRISPR/Cas9 technology and used them as donor cells to generate gene-edited pigs via somatic cell nuclear transfer. The TRBV-edited and wild-type pigs were selected for synchronous ASFV infection. White blood cells were significantly reduced in the genetically modified pigs before ASFV infection. The genetically modified and wild-type pigs were susceptible to ASFV and exhibited typical fevers (>40 °C). However, the TRBV27-edited pigs had a higher viral load than the wild-type pigs. Consistent with this, the gene-edited pigs showed more clinical signs than the wild-type pigs. In addition, both groups of pigs died within 10 days and showed similar severe lesions in organs and tissues. Future studies using lower virulence ASFV isolates are needed to determine the relationship between the TRBV27 gene and ASFV infection in pigs over a relatively long period.