Construction of biochar-based organohalide-respiring bacterial agent for remediation of 2,4,6-trichlorophenol contaminated soil.

Construction of an efficient bio-reductive dechlorination system remains challenging due to the narrow ecological niche and low-growth rate of organohalide-respiring bacteria during field remediation. In this study, a biochar-based organohalide-respiring bacterial agent was obtained, and its performance and effects on indigenous microbial composition, diversity, and inter-relationship in soil were investigated. A well-performing material, Triton X-100 modified biochar (BC600-TX100), was found to have the superior average pore size, specific surface area and hydrophicity, compared to other materials. Interestingly, Pseudomonas aeruginosa CP-1, which is capable of 2,4,6-TCP dechlorination, showed a 348 times higher colonization cell number on BC600-TX100 than that of BC600 after 7 d. Meanwhile, the dechlorination rate in soil showed the highest (0.732 d-1) in the BC600-TX100 bacterial agent than in the other agents. The long-term performance of the BC600-TX100 OHRB agent was also verified, with a stable dechlorination activity over six cycles. Soil microbial community analysis found the addition of the BC600-TX100 OHRB agent significantly increased the relative abundance of genus Pseudomonas from 1.53 % to 11.2 %, and Pseudomonas formed a close interaction relationship with indigenous microorganisms, creating a micro-ecological environment conducive to reductive dechlorination. This study provides a feasible bacterial agent for the in-situ bioremediation of soil contaminated organohalides. ENVIRONMENTAL IMPLICATION: Halogenated organic compounds are a type of toxic, refractory, and bio-accumulative persistent compounds widely existed in environment, widely detected in the air, water, and soil. In this study, we provide a feasible bacterial agent for the in-situ bioremediation of soil contaminated halogenated organic compounds. The application of biochar provides new insights for "Turning waste into treasure", which meets with the concept of green chemistry.

Integrated network pharmacology and metabolomics reveal vascular protective effects of Ilex pubescens on thromboangiitis obliterans.

BACKGROUND: Ilex pubescens Hook. et Arn (IP), traditionally known for its properties of promoting blood circulation, swelling and pain relief, heat clearing, and detoxification, has been used in the treatment of thromboangiitis obliterans (TAO). Despite its traditional applications, the specific mechanisms by which IP exerts its therapeutic effects on TAO remain unclear. AIM OF THE STUDY: This study aims to uncover the underlying mechanisms in the therapeutic effects of IP on TAO, employing network pharmacology and metabolomic approaches. METHODS: In this study, a rat TAO model was established by injecting sodium laurate through the femoral artery, followed by the oral administration of IP for 7 days. Plasma coagulation parameters were measured to assess the therapeutic effects of IP. The potential influence on the femoral artery and gastrocnemius muscle was histopathologically evaluated. Network pharmacology was employed to predict relevant targets and model pathways for TAO. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) was used for the metabolic profile analysis of rat plasma. Immunohistochemistry (IHC) was used to verify the mechanisms by which IP promotes blood circulation in TAO. RESULTS: The study revealed that IP improved blood biochemical function in TAO and played a significant role in vascular protection and maintaining normal blood vessels and gastrocnemius morphologies. Network pharmacology showed that IP compounds play a therapeutic role in modulating lipids and atherosclerosis. Metabolomic analysis revealed that the pathways involved in sphingolipid metabolism and steroid biosynthesis were significantly disrupted. The joint analysis showed a strong correlation between lysophosphatidylcholine and IP components, including triterpenoid and iridoid components, which support the curative action of IP through the modulation of sphingolipid metabolism. Furthermore, decreased expression levels of SPHK1/S1PR1, TNF-α, IL-1ß, and IL-6 were observed in the IP-treated group, suggesting that IP exerts a protective effect on the vasculature primarily by regulating of the SPHK1/S1PR1 signaling pathway. CONCLUSION: In this study, we found that IP protects the vasculature against injury and treats TAO by regulating the steady-state disturbance of the sphingolipid pathway. These findings suggest that IP promotes vasculature by modulating sphingolipid metabolism and SPHK1/S1PR1 signaling pathway and reduce levels of inflammatory factors, offering new insights into its therapeutic potential.

Identification of mulberry leaf flavonoids and evaluating their protective effects on H2O2-induced oxidative damage in equine skeletal muscle satellite cells.

Introduction: Horses are susceptible to oxidative stress during strenuous endurance exercise, leading to muscle fatigue and damage. Mulberry leaf flavonoids (MLFs) possess significant antioxidant properties. However, the antioxidant efficacy of MLFs can be influenced by the extraction process, and their impact on H2O2-induced oxidative stress in equine skeletal muscle satellite cells (ESMCs) remains unexplored. Methods: Our study employed three extraction methods to obtain MLFs: ultrasound-assisted extraction (CEP), purification with AB-8 macroporous resin (RP), and n-butanol extraction (NB-EP). We assessed the protective effects of these MLFs on H2O2-induced oxidative stress in ESMCs and analyzed the MLF components using metabolomics. Results: The results revealed that pre-treatment with MLFs dose-dependently protected ESMCs against H2O2-induced oxidative stress. The most effective concentrations were 0.8 mg/mL of CEP, 0.6 mg/mL of RP, and 0.6 mg/mL of NB-EP, significantly enhancing EMSC viability (p < 0.05). These optimized MLF concentrations promoted the GSH-Px, SOD and T-AOC activities (p < 0.05), while reducing MDA production (p < 0.05) in H2O2-induced ESMCs. Furthermore, these MLFs enhanced the gene expression, including Nrf2 and its downstream regulatory genes (TrxR1, GPX1, GPX3, SOD1, and SOD2) (p < 0.05). In terms of mitochondrial function, ESMCs pre-treated with MLFs exhibited higher basal respiration, spare respiratory capacity, maximal respiration, ATP-linked respiration compared to H2O2-induced ESMCs (p < 0.05). Additionally, MLFs enhanced cellular basal glycolysis, glycolytic reserve, and maximal glycolytic capacity (p < 0.05). Metabolomics analysis results revealed significant differences in mulberrin, kaempferol 3-O-glucoside [X-Mal], neohesperidin, dihydrokaempferol, and isobavachalcone among the three extraction processes (p < 0.05). Discussion: Our study revealed that MLFs enhance antioxidant enzyme activity, alleviate oxidative damage in ESMCs through the activation of the Nrf2 pathway, and improve mitochondrial respiration and cell energy metabolism. Additionally, we identified five potential antioxidant flavonoid compounds, suggesting their potential incorporation into the equine diet as a strategy to alleviate exercise-induced oxidative stress.

The therapeutic effects of ADSCs on photoaging of skin induced by UVB irradiation.

Skin photoaging affects appearance and is associated with a variety of skin diseases, even skin cancer. Therefore, the prevention and treatment of skin photoaging is very important. However, there is a lack of effective evaluation methods, so it is an urgent problem to explore a comprehensive, non-invasive and in vivo evaluation method. Adipose-derived mesenchymal stem cells (ADSCs) are widely used to improve skin conditions as easier to obtain and positive effects. Recently, as the development of ultrasound technology, skin ultrasound has been widely used. Changes in skin layer and structure can be observed by high-frequency ultrasound (HFUS). In addition, Shear wave elastography (SWE) technology can be used to monitor the change of skin hardness. However, it is necessary to further explore the ultrasound parameters in interpreting histological changes. We simulate the progression and treatment process of human skin photoaging by using UVB-induced nude mice skin photoaging model and ADSCs injection. The analysis of the degree and therapeutic effect of skin photoaging was conducted by HFUS, SWE and to verify with histopathology. Our study aims to clarify the value of HFUS combined SWE techniques in evaluating the degree and therapeutic efficacy of skin photoaging, which provides theoretical basis for diagnosis and treatment evaluation systems.

Quantitative Comparison of Liver Volume, Proton Density Fat Fraction, and Time Burden between Automatic Whole Liver Segmentation and Manual Sampling MRI Strategies for Diagnosing Metabolic Dysfunction-associated Steatotic Liver Disease in Obese Patients.

BACKGROUND: The performance of automatic liver segmentation and manual sampling MRI strategies needs be compared to determine interchangeability. OBJECTIVE: To compare automatic liver segmentation and manual sampling strategies (manual whole liver segmentation and standardized manual region of interest) for performance in quantifying liver volume and MRI-proton density fat fraction (MRI-PDFF), identifying steatosis grade, and time burden. METHODS: Fifty patients with obesity who underwent liver biopsy and MRI between December 2017 and November 2018 were included. Sampling strategies included automatic and manual whole liver segmentation and 4 and 9 large regions of interest. Intraclass correlation coefficient (ICC), Bland-Altman, linear regression, receiver operating characteristic curve, and Pearson correlation analyses were performed. RESULTS: Automatic whole liver segmentation liver volume and manual whole liver segmentation liver volume showed excellent agreement (ICC=0.97), high correlation (R2=0.96), and low bias (3.7%, 95% limits of agreement, -4.8%, 12.2%) in liver volume. There was the best agreement (ICC=0.99), highest correlation (R2=1.00), and minimum bias (0.84%, 95% limits of agreement, -0.20%, 1.89%) between automated whole liver segmentation MRI-PDFF and manual whole liver segmentation MRI-PDFF. There was no difference of each paired comparison of receiver operating characteristic curves for detecting steatosis (P=0.07-1.00). The minimum time burden for automatic whole liver segmentation was 0.32 s (0.32-0.33 s). CONCLUSION: Automatic measurement has similar effects to manual measurement in quantifying liver volume, MRI-PDFF, and detecting steatosis. Time burden of automatic whole liver segmentation is minimal among all sampling strategies. Manual measurement can be replaced by automatic measurement to improve quantitative efficiency.

Value of radiological depth of invasion in non-pT4 Oral tongue squamous cell carcinoma: implication for preoperative MR T-staging.

OBJECTIVE: The prognostic stratification for oral tongue squamous cell carcinoma (OTSCC) is heavily based on postoperative pathological depth of invasion (pDOI). This study aims to propose a preoperative MR T-staging system based on tumor size for non-pT4 OTSCC. METHODS: Retrospectively, 280 patients with biopsy-confirmed, non-metastatic, pT1-3 OTSCC, treated between January 2010 and December 2017, were evaluated. Multiple MR sequences, including axial T2-weighted imaging (WI), unenhanced T1WI, and axial, fat-suppressed coronal, and sagittal contrast-enhanced (CE) T1WI, were utilized to measure radiological depth of invasion (rDOI), tumor thickness, and largest diameter. Intra-class correlation (ICC) and univariate and multivariate analyses were used to evaluate measurement reproducibility, and factors' significance, respectively. Cutoff values were established using an exhaustive method. RESULTS: Intra-observer (ICC = 0.81-0.94) and inter-observer (ICC = 0.79-0.90) reliability were excellent for rDOI measurements, and all measurements were significantly associated with overall survival (OS) (all p < .001). Measuring the rDOI on axial CE-T1WI with cutoffs of 8 mm and 12 mm yielded an optimal MR T-staging system for rT1-3 disease (5-year OS of rT1 vs rT2 vs rT3: 94.0% vs 72.8% vs 57.5%). Using multivariate analyses, the proposed T-staging exhibited increasingly worse OS (hazard ratio of rT2 and rT3 versus rT1, 3.56 [1.35-9.6], p = .011; 4.33 [1.59-11.74], p = .004; respectively), which outperformed pathological T-staging based on nonoverlapping Kaplan-Meier curves and improved C-index (0.682 vs. 0.639, p < .001). CONCLUSIONS: rDOI is a critical predictor of OTSCC mortality and facilitates preoperative prognostic stratification, which should be considered in future oral subsite MR T-staging. CLINICAL RELEVANCE STATEMENT: Utilizing axial CE-T1WI, an MR T-staging system for non-pT4 OTSCC was developed by employing rDOI measurement with optimal thresholds of 8 mm and 12 mm, which is comparable with pathological staging and merits consideration in future preoperative oral subsite planning. KEY POINTS: • Tumor morphology, measuring sequences, and observers could impact MR-derived measurements and compromise the consistency with histology. • MR-derived measurements, including radiological depth of invasion (rDOI), tumor thickness, and largest diameter, have a prognostic impact on OS (all p < .001). • rDOI with cutoffs of 8 mm and 12 mm on axial CE-T1WI is an optimal predictor of OS and could facilitate risk stratification in non-pT4 OTSCC disease.

Natural resistance-associated macrophage proteins are involved in tolerance to heavy metal Cd2+ toxicity and resistance to bacterial wilt of peanut (Arachis hypogaea L.).

Peanut (Arachis hypogaea L.) is one of the most important oil and industrial crops. However, heavy-metal pollution and frequent soil diseases, poses a significant threat to the production of green and healthy peanuts. Herein, we investigated the effects of heavy metal Cd2+ toxicity to the peanuts, and screened out two peanut cultivars H108 and YZ 9102 with higher Cd2+-tolerance. RNA-seq revealed that Natural resistance-associated macrophage proteins (NRAMP)-like genes were involved in the Cd2+ stress tolerance in H108. Genome-wide identification revealed that 28, 13 and 9 Nramp-like genes existing in the A. hypogaea, A. duranensis and A. ipaensis, respectively. The 50 peanut NRAMP genes share conserved architectural characters, and they were classified into two groups. Expressions of AhNramps, particularly AhNramp4, AhNramp12, AhNramp19, and AhNramp25 could be greatly induced by not only cadmium toxicity, but also copper and zinc stresses. The expression profiles of AhNramp14, AhNramp16 and AhNramp25 showed significant differences in the H108 (resistance) and H107 (susceptible) under the infection of bacterial wilt. In addition, we found that the expression profiles of AhNramp14, AhNramp16, and AhNramp25 were greatly up- or down-regulated by the application of exogenous salicylic acid, methyl jasmonate, and abscisic acid. The AhNramp25, of which expression was affected by both heavy metal toxicity and bacterial wilt infection, were selected as strong candidate genes for peanut stress breeding. Our findings will provide an additional information required for further analysis of AhNramps involved in tolerance to heavy metal toxicity and resistance to bacterial wilt of peanut.

Dynamic N6 -methyladenosine RNA modification regulates peanut resistance to bacterial wilt.

N6 -methyladenosine (m6 A) is the most abundant mRNA modification in eukaryotes and is an important regulator of gene expression as well as many other critical biological processes. However, the characteristics and functions of m6 A in peanut (Arachis hypogea L.) resistance to bacterial wilt (BW) remain unknown. Here, we analyzed the dynamic of m6 A during infection of resistant (H108) and susceptible (H107) peanut accessions with Ralstonia solanacearum (R. solanacearum), the causative agent of BW. Throughout the transcriptome, we identified 'URUAY' as a highly conserved motif for m6 A in peanut. The majority of differential m6 A located within the 3' untranslated region (UTR) of the transcript, with fewer in the exons. Integrative analysis of RNA-Seq and m6 A methylomes suggests the correlation between m6 A and gene expression in peanut R. solanacearum infection, and functional analysis reveals that m6 A-associated genes were related to plant-pathogen interaction. Our experimental analysis suggests that AhALKBH15 is an m6 A demethylase in peanut, leading to decreased m6 A levels and upregulation of the resistance gene AhCQ2G6Y. The upregulation of AhCQ2G6Y expression appears to promote BW resistance in the H108 accession.

Optimal Size Threshold for MRI-Detected Retropharyngeal Lymph Nodes to Predict Outcomes in Nasopharyngeal Carcinoma: A Two-Center Study.

BACKGROUND. Retropharyngeal lymph node (RLN) metastases have profound prognostic implications in patients with nasopharyngeal carcinoma (NPC). However, the AJCC staging system does not specify a size threshold for determining RLN involvement, resulting in inconsistent thresholds in practice. OBJECTIVE. The purpose of this article was to determine the optimal size threshold for determining the presence of metastatic RLNs on MRI in patients with NPC, in terms of outcome predictions. METHODS. This retrospective study included 1752 patients (median age, 46 years; 1297 men, 455 women) with NPC treated by intensity-modulated radiotherapy (RT) from January 2010 to March 2014 from two hospitals; 438 patients underwent MRI 3-4 months after treatment. Two radiologists measured the minimal axial diameter (MAD) of the largest RLN for each patient using a consensus process. A third radiologist measured MAD in 260 randomly selected patients to assess interobserver agreement. Initial ROC and restricted cubic spline (RCS) analyses were used to derive an optimal MAD threshold for predicting progression-free survival (PFS). The threshold's predictive utility was assessed in multivariable Cox regression analyses, controlling for standard clinical predictors. The threshold's utility for predicting PFS and overall survival (OS) was compared with a 5-mm threshold using Kaplan-Meier curves and log-rank tests. RESULTS. The intraclass correlation coefficient for MAD was 0.943. ROC and RCS analyses yielded an optimal threshold of 6 mm. In multivariable analyses, MAD of 6 mm and greater independently predicted PFS in all patients (HR = 1.35, p = .02), patients with N0 or N1 disease (HR = 1.80, p = .008), and patients who underwent posttreatment MRI (HR = 1.68, p = .04). In patients with N1 disease without cervical lymph node involvement, 5-year PFS was worse for MAD greater than or equal to 6 mm than for MAD that was greater than or equal to 5 mm but less than 6 mm (77.2% vs 89.7%, p = .03). OS was significantly different in patients with stage I and stage II disease defined using a 6-mm threshold (p = .04), but not using a 5-mm threshold (p = .09). The 5-year PFS rate was associated with a post-RT MAD of 6 mm and greater (HR = 1.68, p = .04) but not a post-RT MAD greater than or equal to 5 mm (HR = 1.09, p = .71). CONCLUSION. The findings support a threshold MAD of 6 mm for determining RLN involvement in patients with NPC. CLINICAL IMPACT. Future AJCC staging updates should consider incorporation of the 6-mm threshold for N-category and tumor-stage determinations.

TLR9-independent CD8+ T cell responses in hepatic AAV gene transfer through IL-1R1-MyD88 signaling.

Upon viral infection of the liver, CD8+ T cell responses may be triggered despite the immune suppressive properties that manifest in this organ. We sought to identify pathways that activate responses to a neoantigen expressed in hepatocytes, using adeno-associated viral (AAV) gene transfer. It was previously established that cooperation between plasmacytoid dendritic cells (pDCs), which sense AAV genomes by Toll-like receptor 9 (TLR9), and conventional DCs promotes cross-priming of capsid-specific CD8+ T cells. Surprisingly, we find local initiation of a CD8+ T cell response against antigen expressed in ∼20% of murine hepatocytes, independent of TLR9 or type I interferons and instead relying on IL-1 receptor 1-MyD88 signaling. Both IL-1α and IL-1ß contribute to this response, which can be blunted by IL-1 blockade. Upon AAV administration, IL-1-producing pDCs infiltrate the liver and co-cluster with XCR1+ DCs, CD8+ T cells, and Kupffer cells. Analogous events were observed following coagulation factor VIII gene transfer in hemophilia A mice. Therefore, pDCs have alternative means of promoting anti-viral T cell responses and participate in intrahepatic immune cell networks similar to those that form in lymphoid organs. Combined TLR9 and IL-1 blockade may broadly prevent CD8+ T responses against AAV capsid and transgene product.

Removal of cadmium from aqueous solution by magnetic biochar: adsorption characteristics and mechanism.

Experiments were conducted to investigate the potential of the efficient resource utilization of waste cow manure and corn straw in an agricultural ecosystem. In this study, a magnetic cow manure and straw biochar were synthesized by a co-precipitation method, and cadmium (Cd(II)) was removed by adsorption in aqueous solution. Several physicochemical characterization techniques were applied, including SEM, BET, Zeta, FTIR, Raman, XPS, and VSM. The effects of pH value, magnetic biochar content, adsorption kinetics, and isothermal adsorption on the adsorption of Cd(II) were investigated. The physicochemical characterizations revealed that the physical and chemical properties of the magnetic biochar were substantially changed compared to the unmodified biochar. The results showed that the surface of the biochar became rough, the number of oxygen (O)-containing functional groups increased, and the specific surface area increased. The results of the adsorption experiments showed that the adsorption capacity was affected by pH, magnetic biochar addition, Cd(II) concentration, and adsorption time. The adsorption kinetics and isothermal adsorption experiments showed that the Cd(II) adsorption processes of the cow manure and corn straw magnetic biochars were consistent with the Freundlich model and pseudo-second-order kinetic model. The results also showed that the Cd(II) adsorption effect of cow manure magnetic biochar was found to be more effective than that of corn straw magnetic biochar. The optimal conditions for Cd(II) adsorption were 800 ℃ for cow manure magnetic biochar, with a pH value of 5 and 0.14 g biochar addition, and 600 ℃ for straw magnetic biochar with a pH value of 8 and 0.12 g biochar addition. In conclusion, the cow manure magnetic biochar was an effective adsorbent for the absorption of Cd(II) in wastewater.

Coordinated Lipid Mobilization during Seed Development and Germination in Peanut (Arachis hypogaea L.).

Peanut (Arachis hypogaea L.) is one of the most important oil crops in the world due to its lipid-rich seeds. Lipid accumulation and degradation play crucial roles in peanut seed maturation and seedling establishment, respectively. Here, we utilized lipidomics and transcriptomics to comprehensively identify lipids and the associated functional genes that are important in the development and germination processes of a large-seed peanut variety. A total of 332 lipids were identified; triacylglycerols (TAGs) and diacylglycerols were the most abundant during seed maturation, constituting 70.43 and 16.11%, respectively, of the total lipids. Significant alterations in lipid profiles were observed throughout seed maturation and germination. Notably, TAG (18:1/18:1/18:2) and (18:1/18:2/18:2) peaked at 23386.63 and 23392.43 nmol/g, respectively, at the final stage of seed development. Levels of hydroxylated TAGs (HO-TAGs) increased significantly during the initial stage of germination. Accumulation patterns revealed an inverse relationship between free fatty acids and TAGs. Lipid degradation was determined to be regulated by diacylglycerol acyltransferase, triacylglycerol lipase, and associated transcription factors, predominantly yielding oleic acid, linoleic acid, and linolenic acid. Collectively, the results of this study provide valuable insights into lipid dynamics during the development and germination of large-seed peanuts, gene resources, and guiding future research into lipid accumulation in an economically important crop.

On the optimization of 3D inflow-based vascular-space-occupancy (iVASO) MRI for the quantification of arterial cerebral blood volume (CBVa).

PURPOSE: The inflow-based vascular-space-occupancy (iVASO) MRI was originally developed in a single-slice mode to measure arterial cerebral blood volume (CBVa). When vascular crushers are applied in iVASO, the signals can be sensitized predominantly to small pial arteries and arterioles. The purpose of this study is to perform a systematic optimization and evaluation of a 3D iVASO sequence on both 3 T and 7 T for the quantification of CBVa values in the human brain. METHODS: Three sets of experiments were performed in three separate cohorts. (1) 3D iVASO MRI protocols were compared to single-slice iVASO, and the reproducibility of whole-brain 3D iVASO MRI was evaluated. (2) The effects from different vascular crushers in iVASO were assessed. (3) 3D iVASO MRI results were evaluated in arterial and venous blood vessels identified using ultrasmall-superparamagnetic-iron-oxides-enhanced MRI to validate its arterial origin. RESULTS: 3D iVASO scans showed signal-to-noise ratio (SNR) and CBVa measures consistent with single-slice iVASO with reasonable intrasubject reproducibility. Among the iVASO scans performed with different vascular crushers, the whole-brain 3D iVASO scan with a motion-sensitized-driven-equilibrium preparation with two binomial refocusing pulses and an effective TE of 50 ms showed the best suppression of macrovascular signals, with a relatively low specific absorption rate. When no vascular crusher was applied, the CBVa maps from 3D iVASO scans showed large CBVa values in arterial vessels but well-suppressed signals in venous vessels. CONCLUSION: A whole-brain 3D iVASO MRI scan was optimized for CBVa measurement in the human brain. When only microvascular signals are desired, a motion-sensitized-driven-equilibrium-based vascular crusher with binomial refocusing pulses can be applied in 3D iVASO.

Biomolecular insights into the inhibition of heavy metals on reductive dechlorination of 2,4,6-trichlorophenol in Pseudomonas sp. CP-1.

Influences of heavy metal exposure to the organohalide respiration process and the related molecular mechanism remain poorly understood. In this study, a non-obligate organohalide respiring bacterium, Pseudomonas sp. strain CP-1, was isolated and its molecular response to the five types of commonly existed heavy metal ions were thoroughly investigated. All types of heavy metal ions posed inhibitory effects on 2,4,6-trichlorophenol dechlorination activity and cell growth with the varied degree. Exposure to Cu (II) showed the most serious inhibitive effects on dechlorination even at the lowest concentration of 0.05 mg/L, while the inhibition by As (V) was the least with the removal kinetic constant k decreased to 0.05 under 50 mg/L. Further, multi-omics analysis found compared with Cu (II), As (V) exposure led to the insignificant downregulation of a variety of biosynthesis processes, which would be one possible account for the less inhibited activity. More importantly, the inhibited mechanisms on the organohalide respiration catabolism of strain CP-1 were firstly revealed. Cu (II) stress severely downregulated NADH generation during TCA cycle and electron donation of organohalide respiration process, which might decrease the reducing power required for organohalide respiration. While both Cu (II) and As (Ⅴ) inhibited substrate level phosphorylation during TCA cycle, as well as electron transfer and ATP generation during organohalide respiration. Meanwhile, CprA-2 was confirmed as the responsible reductive dehalogenase in charge of 2,4,6-TCP dechlorination, and transcriptional and proteomic studies confirmed the directly inhibited gene transcription and expression of CprA-2. The in-depth reveal of inhibitory effects and mechanism gave theoretical supports for alleviating heavy metal inhibition on organohalide respiration activity in groundwater co-contaminated with organohalides and heavy metals.

ZSP1601, a novel pan-phosphodiesterase inhibitor for the treatment of NAFLD, A randomized, placebo-controlled phase Ib/IIa trial.

Non-alcoholic fatty liver disease is a growing health burden with limited treatment options worldwide. Herein we report a randomized, double-blind, placebo-controlled, multiple-dose trial of a first-in-class pan-phosphodiesterase inhibitor ZSP1601 in 36 NAFLD patients (NCT04140123). There were three cohorts. Each cohort included twelve patients, nine of whom received ZSP1601 50 mg once daily, 50 mg twice daily, or 100 mg twice daily, and three of whom received matching placebos for 28 days. The primary outcomes were the safety and tolerability of ZSP1601. A total of 27 (27/36, 75%) patients experienced at least one treatment-emergent adverse event (TEAE). Most TEAEs were mild to moderate. There was no Serious Adverse Event. Diarrhea, transiently elevated creatinine and adaptive headache were frequently reported adverse drug reaction. We conclude that ZSP1601 is well-tolerated and safe, showing effective improvement in liver chemistries, liver fat content and fibrosis in patients with NAFLD.

Acoustic Noise Levels in High-field Magnetic Resonance Imaging Scanners.

7-Tesla (T) magnetic resonance imaging may allow for higher resolution images but may produce greater acoustic noise than 1.5- and 3-T scanners. We sought to characterize the intensity of acoustic noise from 7- versus 3-T scanners. A-weighted sound pressure levels from 5 types of pulse sequences used for brain and inner ear imaging in 3- and 7-T scanners were measured. Time-averaged sound level and maximum sound levels generated for each sequence were compared. Time-averaged sound levels exceeded 95 dB and reached maximums above 105 dB on the majority of 3- and 7-T scans. The mean time-averaged sound level and maximum sound level across pulse sequences were greater in 7- than 3-T (105.6 vs 91.4, P = .01; 114.0 vs. 96.5 dB, P < .01). 7- and 3-T magnetic resonance imaging scanners produce high levels of acoustic noise that exceed acceptable safety limits, emphasizing the need for active and passive noise protection.

Impact of China's carbon emissions trading scheme on urban air quality: a time-varying DID model.

Using panel data for 277 Chinese cities, this paper applies a time-varying difference-in-differences (DID) model to empirically test the impact of China's carbon emissions trading scheme (ETS) on urban air quality, and further explores its heterogeneity and the mechanisms involved. The results show that ETS can improve urban air quality. This conclusion remains robust through a series of robustness tests, including PSM-DID estimation, varying window periods, exclusion of significant events, lag phase, and placebo tests. The dynamic effect test indicates that ETS has a continuous and effective effect on improving urban air quality. Mechanism analysis reveals that the degree of marketization can enhance the improvement effect that ETS has on urban air quality. Meanwhile, industrial structure upgrading and green technology innovation are important mechanisms by which pilot ETS policy improves urban air quality. Regional heterogeneity analysis finds that ETS only improves urban air quality in eastern and central regions.

Insights into the Transcriptome of Human Cytomegalovirus: A Comprehensive Review.

Human cytomegalovirus (HCMV) is a widespread pathogen that poses significant risks to immunocompromised individuals. Its genome spans over 230 kbp and potentially encodes over 200 open-reading frames. The HCMV transcriptome consists of various types of RNAs, including messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs), with emerging insights into their biological functions. HCMV mRNAs are involved in crucial viral processes, such as viral replication, transcription, and translation regulation, as well as immune modulation and other effects on host cells. Additionally, four lncRNAs (RNA1.2, RNA2.7, RNA4.9, and RNA5.0) have been identified in HCMV, which play important roles in lytic replication like bypassing acute antiviral responses, promoting cell movement and viral spread, and maintaining HCMV latency. CircRNAs have gained attention for their important and diverse biological functions, including association with different diseases, acting as microRNA sponges, regulating parental gene expression, and serving as translation templates. Remarkably, HCMV encodes miRNAs which play critical roles in silencing human genes and other functions. This review gives an overview of human cytomegalovirus and current research on the HCMV transcriptome during lytic and latent infection.

Dynamic DNA methylation modification in peanut seed development.

Cytosine methylation is an important epigenetic modification involved in regulation of plant development. However, the epigenetic mechanisms governing peanut seed development remain unclear. Herein, we generated DNA methylation profiles of developmental seeds of peanut H2014 and its smaller seed mutant H1314 at 15 and 60 days after pegging (DAP, S1, S4). Accompanying seed development, globally elevated methylation was observed in both lines. The mutant had a higher methylation level of 31.1% than wild type at S4, and 27.1-35.9% of the differentially methylated regions (DMRs) between the two lines were distributed in promoter or genic regions at both stages. Integrated methylome and transcriptome analysis revealed important methylation variations closely associated with seed development. Furthermore, some genes showed significantly negative correlation of expression with the methylation level within promoter or gene body. The results provide insights into the roles of DNA methylation in peanut seed development.