Digital transformation of the agricultural industry: Behavioral decision-making, influencing factors, and simulation practices in the Yunnan highlands.

Motivating the agricultural industry to engage in digital transformation is a challenge academically and socially. It is of great significance to study the choice of digital transformation mode of agricultural industrial organization and analyze its driving factors for promoting the sustainable development of agricultural industrial organization. This study adopts a bilateral evolutionary game to construct a decision-making model for behavioral decision-making during the digital transformation of the agricultural industry. The contingent-actual logical framework and multiple case studies of Yunnan highland agriculture are used to explore the impact of various factors on behavioral decision-making during the digital transformation of the agricultural industry. Additionally, a simulation analysis is used to verify the validity of the bilateral evolutionary game model. The results demonstrate that: (1) When the agricultural industry chooses "active transformation," behavioral decision-making during the digital transformation of the agricultural industry reaches a Nash equilibrium; (2) transformation costs, industry revenue, and reward and penalty mechanisms are the main driving factors for whether or not the agricultural industry chooses to actively engage in digital transformation; and (3) the probability of active digital transformation increases when agricultural industry organizations obtain higher returns at lower costs. Simultaneously, the higher the government's incentives, the greater the enthusiasm. However, when the penalty is excessive, the digital transformation takes the shape of either passive transformation or forced active transformation. Subsequently, it is necessary to improve the digital transformation planning of the agricultural industry, strengthen this field's cooperation mechanism, and formulate a reasonable reward and penalty system for digital transformation.

Adsorption Performance and Mechanisms of Tetracycline on Clay Minerals in Estuaries and Nearby Coastal Areas.

Clay minerals in sediments have strong adsorption capacities for pollutants, but their role in the distribution of antibiotics in estuaries and nearby coastal areas is unclear. We evaluated the clay mineral montmorillonite (SWy-2) adsorption capacity for tetracycline (TC). We assessed the adsorption capacity of SWy-2 for TC by measuring the removal percentage of 30 mg/L TC over time. The effects of pH and ionic strength on the TC adsorption onto SWy-2 were investigated. We analyzed the kinetics of TC adsorption using a pseudo-second-order model and determined the adsorption isotherm using the Langmuir equation. SWy-2 particles were characterized using zeta potential, Fourier transform infrared (FTIR), and X-ray diffraction (XRD) analyses before and after TC adsorption. The removal percentage of 30 mg/L TC by SWy-2 reached 70.76% within 0.25 h and gradually increased to 78.64% at 6 h. TC adsorption was influenced by pH and ionic strength, where low pH enhanced and high ionic strength reduced the adsorption. The kinetics of TC adsorption followed a pseudo-second-order model, and the adsorption isotherm adhered to the Langmuir equation. The saturated adsorption capacity (qmax) of SWy-2 for TC was 227.27 mg/g. Zeta potential, FTIR, and XRD analyses confirmed that electrostatic interactions and chemical bonds played a significant role in the TC adsorption by SWy-2. SWy-2 clay mineral exhibits a substantial adsorption capacity for TC, indicating its potential as an effective sorbent to mitigate antibiotic contamination in estuaries and nearby coastal areas. The observed effects of pH and ionic strength on TC adsorption have implications for the environmental fate and transport of antibiotics. The pseudo-second-order kinetic model and Langmuir isotherm equation provide valuable insights into the adsorption behavior and capacity of TC on SWy-2. Characterization analyses support the involvement of electrostatic interactions and chemical bonds in the SWy-2-TC adsorption mechanism.

Self-endowed magnetic photocatalysts derived from iron-rich sludge and its recycling in photocatalytic process for tetracycline degradation.

The disposal of iron-rich sludge by landfill or incineration poses environmental risks and wastes resources. The utilization of iron-rich sludge for magnetic material preparation offers a sustainable and resource-efficient solution for its disposal. Herein, self-endowed magnetic photocatalysts were initially prepared by pyrolysis using iron-rich sludge without any additives. The photocatalysts performance were evaluated for tetracycline degradation, with the highest degradation rate of 95.3 % at a concentration of 10 mg·L-1 (pH = 7) within 5 h being achieved for the photocatalyst prepared at 800 °C. The reactive radical species in the photocatalysis process were confirmed to be •OH and O2•- activated by ferrous oxygen species under light irradiation. Furthermore, quinone-like structures induced bound persistent free radicals, which emerged as the predominant factors influencing 1O2 formation. The employed photocatalyst can be efficiently separated and recovered owing to its magnetism. This work presents an economic solution for antibiotic removal using waste iron-rich sludge.

Relationship between autism and brain cortex surface area: genetic correlation and a two-sample Mendelian randomization study.

BACKGROUND: Alterations in surface area (SA) in specific regions of the cortex have been reported in many individuals with autism spectrum disorder (ASD), however, the genetic background between ASD and SA is still unclear. This study estimated the genetic correlation and causal effect of ASD and cortical SA. METHODS: Summarized data of genome-wide association studies (GWAS) were separately downloaded from the Psychiatric Genomics Consortium (18,381 cases of ASD, and 27,969 controls) and the Enhancing Neuroimaging Genetics through Meta-Analysis Consortium (33,992 participants of Europeans). We used Linkage disequilibrium score regression (LDSC) and Heritability Estimation from Summary Statistics (HESS) to calculate the heritability of each trait. As for the genetic correlation between ASD and SA, LDSC was used for global correlation and HESS was used to examine the local genetic covariance further. We used three Mendelian randomization (MR) methods, Inverse-variance weighted, MR-Egger, and weighted median to estimate the causal relationship. RESULTS: LDSC observed a nominal significant genetic correlation (rg = 0.1229, P-value = 0.0346) between ASD and SA of the rostral anterior cingulate gyrus whereas analysis through HESS did not reveal any significant loci having genetic covariance. Based on MR results, statistically meaningful estimations were found in the following areas, postcentral cortex (ß (SE) = 21.82 (7.84) mm, 95% CI: 6.46 to 37.19 mm, PIVW = 5.38 × 10- 3, PFDR = 3.09 × 10- 2), posterior cingulate gyrus (ß (SE) = 6.23 (2.69) mm, 95% CI: 0.96 to 11.49 mm, PIVW = 2.05 × 10- 2, PFDR = 4.26 × 10- 2), supramarginal gyrus (ß (SE) = 19.25 (8.43) mm, 95% CI: 29.29 to 35.77 mm, PIVW = 2.24 × 10- 2, PFDR = 4.31 × 10- 2). CONCLUSION: Our results provided genetic evidence to support the opinion that individuals with ASD tend to develop differences in cortical SA of special areas. The findings contributed to understanding the genetic relationship between ASD and cortical SA.

Enhanced Adsorptive Removal of Tetracycline by Phosphomolybdic Acid-Modified Low-Temperature Sludge Biochar.

Increasing the adsorption capacity and reducing the energy consumption of sludge biochar during preparation is important. In this study, a new modification method was developed to prepare phosphomolybdic acid-modified sludge biochar through the low-temperature pyrolysis of sewage sludge using phosphomolybdic acid as a modifier. Tetracycline was used to assess the adsorption performance of sludge biochar, and phosphomolybdic acid-modified sludge biochar was prepared at different temperatures. The results showed that the adsorption capacity of sludge biochar improved from 84.49 to 120.86 mg/g through modification with phosphomolybdic acid at 200 °C. The maximum adsorption capacities of phosphomolybdic acid-modified sludge biochar (200 °C pyrolysis temperature) at 298, 308, and 318 K were 283.87, 421.39, and 545.48 mg/g, respectively. Both liquid film and intraparticle diffusion were the main rate-limiting steps of tetracycline adsorption by phosphomolybdic acid-modified sludge biochar. Furthermore, the adsorption of tetracycline by phosphomolybdic acid-modified sludge biochar was mainly attributed to π-π interactions, electrostatic interactions, hydrogen bonding, and pore filling.

Integrative analysis of long noncoding RNAs dysregulation and synapse-associated ceRNA regulatory axes in autism.

Autism spectrum disorder (ASD) is a complex disorder of neurodevelopment, the function of long noncoding RNA (lncRNA) in ASD remains essentially unknown. In the present study, gene networks were used to explore the ASD disease mechanisms integrating multiple data types (for example, RNA expression, whole-exome sequencing signals, weighted gene co-expression network analysis, and protein-protein interaction) and datasets (five human postmortem datasets). A total of 388 lncRNAs and five co-expression modules were found to be altered in ASD. The downregulated co-expression M4 module was significantly correlated with ASD, enriched with autism susceptibility genes and synaptic signaling. Integrating lncRNAs from the M4 module and microRNA (miRNA) dysregulation data from the literature identified competing endogenous RNA (ceRNA) network. We identified the downregulated mRNAs that interact with miRNAs by the miRTarBase, miRDB, and TargetScan databases. Our analysis reveals that MIR600HG was downregulated in multiple brain tissue datasets and was closely associated with 9 autism-susceptible miRNAs in the ceRNA network. MIR600HG and target mRNAs (EPHA4, MOAP1, MAP3K9, STXBP1, PRKCE, and SCAMP5) were downregulated in the peripheral blood by quantitative reverse transcription polymerase chain reaction analysis (false discovery rate <0.05). Subsequently, we assessed the role of lncRNA dysregulation in altered mRNA levels. Experimental verification showed that some synapse-associated mRNAs were downregulated after the MIR600HG knockdown. BrainSpan project showed that the expression patterns of MIR600HG (primate-specific lncRNA) and synapse-associated mRNA were similar in different human brain regions and at different stages of development. A combination of support vector machine and random forest machine learning algorithms retrieved the marker gene for ASD in the ceRNA network, and the area under the curve of the diagnostic nomogram was 0.851. In conclusion, dysregulation of MIR600HG, a novel specific lncRNA associated with ASD, is responsible for the ASD-associated miRNA-mRNA axes, thereby potentially regulating synaptogenesis.

Spatiotemporal evolution of healthcare service capacity at township health centers in China.

Introduction: This study analyzes the efficiency, spatiotemporal evolution, and influencing factors of provincial township health centers' healthcare service capacity in China. Method: It utilizes an unexpected output super-efficiency slacks-based measure (SBM) model, exploratory spatiotemporal data analysis methods, and a quantile regression model. Results: The results show that the healthcare service capacity of township health centers is better in provinces with a larger proportion of hierarchical diagnoses and treatments pilot projects in cities, and the regional efficiency trend is ordered central > eastern > western > northeastern. The healthcare service capacity of provincial township health centers mainly shows significant spatial correlation and a spatiotemporal distribution pattern of "high agglomeration, low differentiation." Discussion: Rural population density and per capita GDP significantly improve the healthcare service capacity of township health centers, while local governments' healthcare and health expenditure increases the healthcare service capacity of township health centers in certain quantiles. The urbanization rate and per capita disposable income inhibit the improvement of the healthcare service capacity of township health centers in certain quantiles. The provinces should accelerate the promotion of hierarchical diagnoses and treatment pilot projects in cities and establish national cooperative development models to promote public health.

Neuralgic amyotrophy: sensitivity and specificity of magnetic resonance neurography in diagnosis: A retrospective study.

BACKGROUND: Neuralgic amyotrophy (NA) is a clinically acute or subacute disease. To study the characteristics of brachial plexus magnetic resonance neurography (MRN) in patients with NA, and to explore the clinical application value of MRN combined with electromyography (EMG) in the diagnosis of NA. METHODS: Brachial plexus MRN images of 32 patients with NA were retrospectively analyzed, and their characteristics were investigated. The accuracy, sensitivity and specificity of MRN, EMG, and the combination of the 2 methods for NA diagnosis were compared. RESULTS: Among the 32 patients with NA, 28 (87.5%) cases of unilateral brachial plexus involvement, 18 (56.3%) cases of multiple nerve roots involvement. In 10 cases, C5 nerve roots were involved alone, and in 9 cases, C5 to C6 nerve roots were involved together. The T2 signal intensity of the affected nerve increased, and 19 cases showed thickened and smooth nerve root edges. Twelve cases showed uneven thickening and segmental stenosis of the involved nerve roots. The diagnostic accuracy, sensitivity, and specificity of MRN for NA were higher than those of EMG. Combining MRN and EMG could improve the sensitivity and specificity of diagnosis. CONCLUSION: The main feature of MRN in patients with NA was that it was unilateral brachial plexus asymmetric involvement. The diagnostic effect of MRN was better than that of EMG. The combined diagnosis of MRN and EMG can help clinicians diagnose NA accurately.

Calcium Homeostasis and Psychiatric Disorders: A Mendelian Randomization Study.

Observational studies have investigated the impact of calcium homeostasis on psychiatric disorders; however, the causality of associations is yet to be established. Bidirectional Mendelian randomization (MR) analysis of calcium homeostasis hormones was conducted on nine psychiatric disorders. Calcium, serum 25-hydroxyvitamin D levels (25OHD), parathyroid hormone, and fibroblast growth factor 23 are the major calcium homeostasis hormones. The causality was evaluated by the inverse variance weighted method (IVW) and the MR Steiger test, while Cochran's Q test, the MR-Egger intercept test, funnel plot, and the leave-one-out method were used for sensitivity analyses. Bonferroni correction was used to determine the causative association features (p < 6.94 × 10-4). Schizophrenia (SCZ) was significantly associated with decreased 25OHD concentrations with an estimated effect of -0.0164 (Prandom-effect IVW = 2.39 × 10-7). In the Multivariable MR (MVMR) analysis adjusting for potentially confounding traits including body mass index, obesity, mineral supplements (calcium, fish oil, and vitamin D) and outdoor time (winter and summer), the relationship between SCZ and 25OHD remained. The genetically predicted autism spectrum disorder and bipolar disorder were also nominally associated with decreased 25OHD. This study provided evidence for a causal effect of psychiatric disorders on calcium homeostasis. The clinical monitoring of 25OHD levels in patients with psychiatric disorders is beneficial.

Autism spectrum disorder research: knowledge mapping of progress and focus between 2011 and 2022.

Background: In recent years, a large number of studies have focused on autism spectrum disorder (ASD). The present study used bibliometric analysis to describe the state of ASD research over the past decade and identify its trends and research fronts. Methods: Studies on ASD published from 2011 to 2022 were obtained from the Web of Science Core Collection (WoSCC). Bibliometrix, CiteSpace, and VOSviewer were used for bibliometric analysis. Results: A total of 57,108 studies were included in the systematic search, and articles were published in more than 6,000 journals. The number of publications increased by 181.7% (2,623 in 2011 and 7,390 in 2021). The articles in the field of genetics are widely cited in immunology, clinical research, and psychological research. Keywords co-occurrence analysis revealed that "causative mechanisms," "clinical features," and "intervention features" were the three main clusters of ASD research. Over the past decade, genetic variants associated with ASD have gained increasing attention, and immune dysbiosis and gut microbiota are the new development frontiers after 2015. Conclusion: This study uses a bibliometric approach to visualize and quantitatively describe autism research over the last decade. Neuroscience, genetics, brain imaging studies, and gut microbiome studies improve our understanding of autism. In addition, the microbe-gut-brain axis may be an exciting research direction for ASD in the future. Therefore, through visual analysis of autism literature, this paper shows the development process, research hotspots, and cutting-edge trends in this field to provide theoretical reference for the development of autism in the future.

Cervical cancer immune infiltration microenvironment identification, construction of immune scores, assisting patient prognosis and immunotherapy.

Background: The immune microenvironment is of great significance in cervical cancer. However, there is still a lack of systematic research on the immune infiltration environment of cervical cancer. Methods: We obtained cervical cancer transcriptome data and clinical information from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases, evaluated the immune microenvironment of cervical cancer, determined immune subsets, constructed an immune cell infiltration scoring system, screened key immune-related genes, and performed single-cell data analysis and cell function analysis of key genes. Results: We combined the TCGA and GEO data sets and obtained three different immune cell populations. We obtained two gene clusters, extracted 119 differential genes, and established an immune cell infiltration (ICI) scoring system. Finally, three key genes, IL1B, CST7, and ITGA5, were identified, and single-cell sequencing data were mined to distribute these key genes in different cell types. By up-regulating CST7 and down-regulating IL1B and ITGA5, cervical cancer cells' proliferation ability and invasion ability were successfully reduced. Conclusion: We conducted a comprehensive assessment of the state of the tumor immune microenvironment in cervical cancer, constructed the ICI scoring system, and identified the ICI scoring system as a potential indicator of susceptibility to immunotherapy for cervical cancer, identifying key genes suggesting that IL1B, CST7, and ITGA5 play an essential role in cervical cancer.

Radiation-induced gastrointestinal (GI) syndrome as a function of age.

Previous studies show increased sensitivity of older mice (28-29 months) compared with young adult mice (3 months, possessing a mature immune system) to radiation-induced GI lethality. Age-dependent lethality was associated with higher levels of apoptotic stem cells in small intestinal crypts that correlated with sphingomyelinase activity, a source of pro-apoptotic ceramide. The objective of this study is to determine whether the cycling crypt base columnar cells (CBCs) in aging animals are specifically more sensitive to radiation effects than the CBCs in young adult mice, and to identify factors that contribute to increased radiosensitivity. Mortality induced by subtotal body radiation was assessed at different doses (13 Gy, 14 Gy, and 15 Gy) in young adult mice versus older mice. Each dose was evaluated for the occurrence of lethal GI syndrome. A higher death rate due to radiation-induced GI syndrome was observed in older mice as compared with young adult mice: 30 vs. 0% at 13 Gy, 90 vs. 40% at 14 Gy, and 100 vs. 60% at 15 Gy. Radiation-induced damage to crypts was determined by measuring crypt regeneration (H&E staining, Ki67 expression), CBC biomarkers (lgr5 and ascl2), premature senescence (SA-ß-gal activity), and apoptosis of CBCs. At all three doses, crypt microcolony survival assays showed that the older mice had fewer regenerating crypts at 3.5 days post-radiation treatment. Furthermore, in the older animals, baseline CBCs numbers per circumference were significantly decreased, correlating with an elevated apoptotic index. Analysis of tissue damage showed an increased number of senescent CBCs per crypt circumference in older mice relative to younger mice, where the latter was not significantly affected by radiation treatment. It is concluded that enhanced sensitivity to radiation-induced GI syndrome and higher mortality in older mice can be attributed to a decreased capacity to regenerate crypts, presumably due to increased apoptosis and senescence of CBCs.

Reply to Chan et al.

We agree that smoking might be a risk factor for the severity of COVID-19, but in our previous study, smoking was not so robust compared with our conclusion. Also, we strongly agreed that COVID-19 patients with diabetes or other chronic diseases might worsen the situation of the disease. But these factors were out of the scope of our study and we had published other research on this topic related to diabetes. Because of the limited sample size and original medical records, our study could not cover many factors. But we wish our study will be a useful and meaningful pilot study for future studies.

Ascorbic acid enhanced ferrous/persulfate system for degradation of tetracycline contaminated groundwater.

Persulfate (PS) activated by Fe(ii) has been widely investigated for degradation of contaminants. However, the Fe(ii)/PS systems used for actual contaminated groundwater remediation have been restricted by circulation of Fe(iii)/Fe(ii). Herein, an ascorbic acid (AA) enhanced Fe(ii)/PS system was developed for degradation of tetracycline (TC) contaminated groundwater. The influence of Fe(ii), AA, PS dosage and pH on degradation of TC was investigated, the free radicals produced in the reaction were identified and the reusability of Fe(ii) in the Fe(ii)/PS/AA system for degradation of TC was also evaluated. The results showed that AA significantly promoted the degradation of TC in the Fe(ii)/PS system, and a degradation rate of 86% for TC was achieved at 60 min. The dominant oxidant species for contaminant degradation in the Fe(ii)/PS/AA system is ˙OH. Appropriate Fe(ii), AA and PS dosage can improve the degradation rate of TC. Moreover, the degradation rate of TC in the Fe(ii)/PS/AA system under acidic conditions is higher than that under alkaline conditions. With the increase of reaction time, TC can also be completely degraded even with a little Fe(ii) or under alkaline conditions in the Fe(ii)/PS/AA system, and Fe(ii) showed a good reusability for the degradation of TC. Thus, the AA-enhanced Fe(ii)/PS system for the degradation of contaminants displays the advantages of less Fe(ii) consumption and a wide range of pH. This method provides a new strategy for in situ remediation of contaminated groundwater.

The clinical and bioinformatics analysis for the role of antihypertension drugs on mortality among patients with hypertension hospitalized with COVID-19.

Comorbidities such as hypertension could exacerbate symptoms of coronaviral disease 2019 (COVID)-19 infection. Patients with hypertension may receive both anti-COVID-19 and antihypertension therapies when infected with COVID-19. However, it is not clear how different classes of anti-hypertension drugs impact the outcome of COVID-19 treatment. Herein, we explore the association between the inpatient use of different classes of anti-hypertension drugs and mortality among patients with hypertension hospitalized with COVID-19. We totally collected data from 278 patients with hypertension diagnosed with COVID-19 admitted to hospitals in Wuhan from February 1 to April 1, 2020. A retrospective study was conducted and single-cell RNA-sequencing (RNA-Seq) analysis of treatment-related genes was performed. The results showed that Angiotensin II receptor blocker (ARB) and calcium channel blocker (CCB) drugs significantly increased the survival rate but the use of angiotensin-converting enzyme inhibitor/ß-block/diuretic drugs did not affect the mortality caused by COVID-19. Based on the analysis of four public data sets of single-cell RNA-Seq on COVID-19 patients, we concluded that JUN, LST1 genes may play a role in the effect of ARB on COVID-19-related mortality, whereas CALM1 gene may contribute to the effect of CCB on COVID-19-related mortality. Our results provide guidance on the selection of antihypertension drugs for hypertensive patients infected with COVID-19.

Comparing visual preferences between autism spectrum disorder (ASD) and normal children to explore the characteristics of visual preference of ASD children by improved visual preference paradigm: a case-control study.

BACKGROUND: One of features of Visual preference in autism spectrum disorder (ASD) is that they tend to social stimuli to nonsocial stimuli. Though it has been studied widely, until now the results are still not consistent. One of the most important reasons may be that the stimuli of the past visual preference paradigm have different movement patterns. Therefore, the present study aimed to improve the visual preference paradigm to reduce the bias caused by different movement of stimuli and explore the features of visual preference of ASD further. METHODS: Two hundred and seven children who met DSM-5 criteria for ASD and 125 typically developmental (TD) children were enrolled. They were matched in age and gender. Visual preference was measured by eye tracking technology. The subjects presented simultaneously with dynamic object images (DOI) and dynamic social images (DSI) with the same type and same speed of repetitive movement. Social interaction deficits of ASD were assessed by parents with Aberrant Behavior Checklist (ABC). RESULTS: Compared with TD children, the following findings were noted: (I) children with ASD paid less attention to social stimuli and more attention to nonsocial stimuli (t=6.417, P<0.001). (II) Increased preference to DSI was positively correlated with age (R=0.23, P=0.001). (III) No association was noted between visual preference and IQ in children with ASD (R=0.081, P=0.435). (IV) Reduced preference to DSI was negatively correlated with the severity of social interaction impairment rated by parents with ABC in children with ASD (R=0.237, P=0.010). CONCLUSIONS: Children with ASD exhibited abnormal visual preference for social and nonsocial stimuli.

Complement C3aR/C5aR-binding protein Suilysin of Streptococcus suis contributes to monocyte chemotaxis.

Streptococcus suis is an emerging swine and human pathogen causing severe infections and sudden death. During infection, complement C3a and C5a were reported to induce immune cells towards infection and injury sites via their corresponding receptors C3aR and C5aR. However, how S. suis evade immune surveillance mediated by C3aR and C5aR remains unclear. In this study, we analyze and construct an S. suis bacterial two-hybrid prey library containing 39 LPXTG motif anchored proteins and 18 secreted proteins. Two highly possible C3aR-binding proteins: thiol-activated toxin Suilysin, putative RTX family exoprotein A gene and three highly possible C5aR-binding proteins: thiol-activated toxin Suilysin, putative 5'-nucleotidase and subtilisin-like serine protease are identified through bacterial two-hybrid assay. Far-western blot assay confirms that a cholesterol-binding cytolysin Suilysin can interact with both C3aR and C5aR. Chemotaxis assays demonstrate that recombinant and natural Suilysin can inhibit monocyte chemotaxis mediated by C3a and C5a. These findings enlarge our knowledge of suilysin biological significance and provide a new perspective on S. suis complement evasion.

Phenanthrene, but not its isomer anthracene, effectively activates both human and mouse nuclear receptor constitutive androstane receptor (CAR) and induces hepatotoxicity in mice.

Polycyclic aromatic hydrocarbons (PAHs) are a class of pervasive global environmental pollutants and adversely affect human health. Among PAHs, phenanthrene and anthracene are isomers consisting of three benzene rings. In the present study, we have made comparisons of constitutive androstane receptor (CAR) activation and toxic effects on the liver between these two isomers. Phenanthrene, but not anthracene, significantly induced promoter activity and gene expression of human drug metabolizing enzyme CYP2B6 in HepG2 cells and human primary hepatocytes, respectively. Phenanthrene, but not anthracene, significantly increased CYP2B10 expression levels and caused hepatotoxicity in mice. Phenanthrene induced the nuclear accumulation of CAR in the liver of wild-type mice, but not CAR-/- mice. Hepatocellular necrosis, elevated expression levels of some CAR-related genes such as CYP2B10, CYP3A11, UGT1A1, SULT2A1 and GSTM3, and lower hepatic glutathione levels were found in phenanthrene-exposed wild-type mice but not CAR-/- mice. Additionally, phenanthrene and anthracene were detected in both raw and grilled lamb samples. The average concentrations of phenanthrene were much higher than those of anthracene in these samples. This study is the first to demonstrate that phenanthrene, but not its isomer anthracene, effectively activates both human and mouse nuclear receptor CAR, and CAR plays a crucial role in phenanthrene-induced mouse hepatotoxicity. Compared with anthracene, K region may be an important electronic structure of phenanthrene for activation of CAR. Dietary consumption of PAHs-contaminated food is an important exposure route for humans. Exposure to phenanthrene may affect human health especially associated with liver.

Defective fatty acid oxidation in mice with muscle-specific acyl-CoA synthetase 1 deficiency increases amino acid use and impairs muscle function.

Loss of long-chain acyl-CoA synthetase isoform-1 (ACSL1) in mouse skeletal muscle (Acsl1M-/-) severely reduces acyl-CoA synthetase activity and fatty acid oxidation. However, the effects of decreased fatty acid oxidation on skeletal muscle function, histology, use of alternative fuels, and mitochondrial function and morphology are unclear. We observed that Acsl1M-/- mice have impaired voluntary running capacity and muscle grip strength and that their gastrocnemius muscle contains myocytes with central nuclei, indicating muscle regeneration. We also found that plasma creatine kinase and aspartate aminotransferase levels in Acsl1M-/- mice are 3.4- and 1.5-fold greater, respectively, than in control mice (Acsl1flox/flox ), indicating muscle damage, even without exercise, in the Acsl1M-/- mice. Moreover, caspase-3 protein expression exclusively in Acsl1M-/- skeletal muscle and the presence of cleaved caspase-3 suggested myocyte apoptosis. Mitochondria in Acsl1M-/- skeletal muscle were swollen with abnormal cristae, and mitochondrial biogenesis was increased. Glucose uptake did not increase in Acsl1M-/- skeletal muscle, and pyruvate oxidation was similar in gastrocnemius homogenates from Acsl1M-/- and control mice. The rate of protein synthesis in Acsl1M-/- glycolytic muscle was 2.1-fold greater 30 min after exercise than in the controls, suggesting resynthesis of proteins catabolized for fuel during the exercise. At this time, mTOR complex 1 was activated, and autophagy was blocked. These results suggest that fatty acid oxidation is critical for normal skeletal muscle homeostasis during both rest and exercise. We conclude that ACSL1 deficiency produces an overall defect in muscle fuel metabolism that increases protein catabolism, resulting in exercise intolerance, muscle weakness, and myocyte apoptosis.