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RDE is becoming a necessary element of the emissions certification of automotive vehicles. Real Driving Emissions (RDE) helps to ensure that the regular operation of a car, or heavy vehicle, is still within the acceptable emissions standards while driving under normal conditions. RDE is monitored by connecting a Portable Emissions Measurement System (PEMS) to the exhaust of the tested vehicle, which measures the pollutant concentrations as the car or truck drives along a standardised route. The data described in this paper is the raw, detailed PEMS records of a heavy goods vehicle, recorded at a rate of 1Hz, over multiple trips on an urban route in South Africa. The data includes the pollutant concentrations of CO, CO2, NO and NO2, ambient conditions, and vehicle diagnostics collected from different sensors mounted to the vehicle during the field tests. We performed no additional analysis on the data. The value of the data is in allowing researchers to (a) develop and test machine learning algorithms that predict the instantaneous pollutant concentrations or (b) studying the variance of pollutant concentrations that occurs under typical driving conditions.

Multiple spectroscopic, chromatographic, and chemical reaction methods were combined to investigate the chemical components in the fruits of Elaeagnus angustifolia L. As results, thirty-two compounds were obtained from it as natural products. Six of them, elangphenosides A (1), B (2), C (3) and D (4), elangmegastigmanoside A (5), and elangorganic acid A 1 (6) were retrieved by Scifinder as previously undescribed ones. Additionally, a previously undescribed artificial product, elangorganic acid A 2 , as well as a known artificial one, (3R) 5-ethoxy-3-(ethoxycarbonyl)-3-hydroxy-5-oxopentanoic acid, were yielded. Following the phytochemical investigation, LC-MS analysis was employed to conduct a systematical characterization of the constituents from E. angustifolia fruits. Ultimately, fifty-six compounds, including seventeen phenols, one ionone, twenty-four triterpenes, and fourteen other ones, were unambiguously detected and identified. Moreover, in vitro anti-inflammatory activity screening of forty-four natural compounds presented in E. angustifolia fruits was performed by using the LPS-induced RAW264.7 cell model. Twenty-six compounds, including phenols, organic acids, and other compounds, showed assignable activity. Furthermore, their structure-activity relationships were summarized. Combined with the previous research work in our lab, triterpenes, phenols, and organic acids were speculated to be key components during the E. angustifolia fruits exerting anti-inflammatory activity. In summary, this article fully explored the chemical composition of E. angustifolia fruits, assayed their in vitro NO production inhibitory effects, greatly expanding its material foundation and laying a solid foundation for further research and development., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Epidemiological studies have demonstrated exposure to cadmium ion (Cd 2+ ) is significantly associated with the incidence and aggravation of nonalcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH). Cd 2+ exposure could alter lipid metabolism, and changed lipid metabolites are significantly associated with NASH. Arachidonic acid (ArA) is an omega-6 polyunsaturated fatty acid. Promotion of ArA synthesis and profile changes by Cd 2+ exposure potentially to cause NAFLD. ArA metabolism pathway has been identified to enrich in Cd 2+ exposure-facilitated NASH. ArA could be generation an impressive metabolic profile through mainly three pathways, including Cyclooxygenases (COX), Lipoxygenases (LOX) and Cytochrome P450 (CYP450) pathway. However, the functions of these metabolites and underlying mechanism in hepatic inflammation are still not clear. In present study, by integrative transcriptomics and metabolomics analysis, we identified that the fatty acid metabolic process and the pro-inflammatory NF-κB signaling pathway were enriched in Cd 2+ -regulated differentially expressed genes (DEGs) and Cd 2+ -altered differential metabolites, such as, fatty acid biosynthesis, degradation, and ArA metabolism. The metabolites levels of LOX pathway products 5-HETE and leukotriene C4 (LTC4), and COX catalytic product prostaglandin D2 (PGD2) were significantly elevated in Cd 2+ exposed mouse livers. 5-HETE, LTC4, and PGD2 were significantly positive correlated with NF-κB signaling. In addition, the synthase of 20-Hydroxyeicosatetraenoic acid (20-HETE), CYP450 gene 4 family (CYP4A32), was also involved in NF-κB signaling network. Results from both in vitro and in vivo proved that Cd 2+ exposure increased ArA metabolite to PGD2 and 20-HETE, and upregulated the mRNA level of their catalytic enzyme PGDS and CYP4A32. Cd 2+ -induced ArA metabolite to PGD2 and 20-HETE promoted activation of TLR4/IκBα/NF-κB signaling and pro-inflammatory of hepatocytes. Our study explores novel molecular mechanism of Cd 2+ exposure-aggravated liver diseases and provides potential novel targets for in hepatic inflammatory treatments and prevention., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Kam sweet rice is a cultural treasure in Qiandongnan, Guizhou Province. However, the situation with low yield and economic value in Kam sweet rice urgently requires improved mechanistic understanding of tillering to increase its yield. In this study, we found that the rate of axillary bud elongation differed significantly among Kam sweet rice varieties, which was positively correlated with tiller number. Transcriptome analysis suggests that genes involved in nitrogen metabolism and plant hormone signaling pathways could be the main reasons for the differences in tillering among these varieties. The amino acid transporter OsAAP11 in the transcriptome was essential for bud outgrowth and rice tillering based on the phenotypic performance of its transgenic plants. Further results found that OsAAP11 was able to transport amino acids such as proline, glycine, and alanine in rice. Natural variations were found in the promoter region of this gene in different Kam sweet rice varieties, which may lead to differences in the transcription levels of OsAAP11. Overall, the results suggest that the natural variations of OsAAP11 in rice might lead to variations in its expression levels, further affecting bud outgrowth and tillering through regulating the transport and accumulation of amino acids., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Pulmonary hypertension (PH) is a medical condition characterized by elevated pulmonary vascular resistance and pressure, resulting from different diseases. Due to their high occurrence of PH, intricate hemodynamic classification, and frequently multifactorial cause and mechanism, individuals suffering from chronic kidney disease (CKD) are categorized as the fifth primary group of PH. Based on both domestic and international research, this article provides information on the epidemiology, risk factors, pathogenesis, and targeted drug treatment of PH associated with CKD., Competing Interests: Disclosure of COI The authors declare no conflict of interest in this work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Mucin 1 (MUC1) is frequently overexpressed in various cancers and is essential for early cancer detection. Current methods to detect MUC1 are expensive, time-consuming, and require skilled personnel. Therefore, developing a simple, sensitive, highly selective MUC1 detection sensor is necessary. In this study, we proposed a novel "signal-on-off" strategy that, in the presence of MUC1, synergistically integrates catalytic hairpin assembly (CHA) with DNA tetrahedron (Td)-based nonlinear hybridization chain reaction (HCR) to enhance the immobilization of electrochemically active methylene blue (MB) on magnetic nanoparticles (MNP), marking the MB signal "on". Concurrently, the activation of CRISPR-Cas12a by isothermal amplification products triggers the cleavage of single-stranded DNA (ssDNA) at the electrode surface, resulting in a reduction of MgAl-LDH@Fc-AuFe-MIL-101 (containing ferrocene, Fc) on the electrode, presenting the "signal-off" state. Both MB and MgAl-LDH@Fc-AuFe-MIL-101 electrochemical signals were measured and analyzed. Assay parameters were optimized, and sensitivity, stability, and linear range were assessed. Across a concentration spectrum of MUC1 spanning from 10 fg/mL to 100 ng/mL, the MB and MgAl-LDH@Fc-AuFe-MIL-101 signals were calibrated with each other, demonstrating a "signal-on-off" dual electrochemical signaling pattern. This allows for the precise and quantitative detection of MUC1 in clinical samples, offering significant potential for medical diagnosis., Competing Interests: Declaration of competing interest I am authorized on behalf of all the authors of this article to confirm that no author has any conflict of interest to disclose, all authors have approved the version submitted for publication, the work in this article is original and has not been published previously, and the article is not under consideration by any other journal., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Mushroom poisoning poses a significant global health concern, with high morbidity and mortality rates. The primary lethal toxins responsible for this condition are alpha-amanitin (ɑ-AMA) and beta-amanitin (β-AMA). As a promising bio-recognition molecules in biosensors, aptamers, have been broadly used in the field of food detection. However, the current SELEX-based methods for screening aptamers for structurally similar small molecules were limited by the labelling or salt ion induction. In this study, we aimed to develop a novel label-free SELEX strategy for the screening of aptamers with high affinity and constructed new aptasensors for the detection of ɑ-AMA and β-AMA., Results: A novel label-free SELEX strategy based on the positively charged gold nanoparticles (AuNPs) was proposed to simultaneous screening of aptamers for ɑ-AMA and β-AMA. Only 18 rounds of SELEX were required to obtain new aptamers. The candidate aptamers were analyzed by colloidal gold assay, and the sequences of ɑ-30 and β-37 displayed great affinity with Kd values of 22.26 nM and 23.32 nM, respectively, without interference from botanical toxins. Notably, the truncated aptamers ɑ-30-2 (50 bp) and β-37-2 (57 bp) exhibited higher affinity than their original counterpart (79 bp). Subsequently, the selected aptamers were utilized to construct recognition probes for electrochemical aptasensors based on hairpin cyclic cleavage of substrates by Cu 2+ dependent DNAzyme and Exo I-triggered recycling cascades. The detection platform showed excellent analytical performance with limits of detection as low as 4.57 pg/mL (ɑ-AMA) and 8.49 pg/mL (β-AMA). Moreover, the aptasensors exhibited superior performance in mushroom and urine samples., Significance: This work developed a simple and efficient label-free SELEX method for screening new aptamers for ɑ-AMA and β-AMA, which employed the positively charged AuNPs as the screening medium, without the need for chemical labelling of libraries or induction of salt ions. Furthermore, two novel electrochemical aptasensors were developed based on our newly obtained aptamers, which offer the new biosensing tool for ultrasensitive detection of the AMA poisoning, showing great potential in practical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

As one of a traditional Chinese medicine with dual applications in both medicinal treatment and dietary consumption, the mature seeds of D. lablab were reported to be rich in saponins and have a good effect on inflammatory related diseases. However, the substance basis for its anti-inflammatory activity remains unclear. Thus, a comprehensive phytochemical investigation on triterpenoid saponins from D. lablab seeds was carried out, resulting in the isolation and identification of twenty-one new triterpenoid saponins including dolilabsaponins A 1 -A 4 , B, C, D 1 -D 3 , E-M, N 1 , N 2 and O (1-21) along with thirteen known analogs (22-34). Notably, the known saponins, 31, 32, and 34 were obtained from Leguminosae family for the first time. The 1 H and 13 C NMR data of saponins 24 and 28 were firstly reported here. Additionally, lipopolysaccharide (LPS)-stimulated RAW264.7 cells model was utilized to assess inhibitory activities of compounds 1-34 on nitric oxide (NO) production. The results revealed that compounds 1-3, 9, 10, 13-15, 18, 22, 23 and 28-34 significantly suppressed the elevation of NO levels in LPS-induced RAW264.7 cells at the concentration of 30 μM, exhibiting a concentration-dependent manner at 3, 10, and 30 μM. The results suggested that compounds 1-3, 9, 10, 13-15, 18, 22, 23, and 28-34 possessed potential anti-inflammatory activity. Further western blot assay demonstrated that 1, 9, 10, 13, 14, and 18 suppressed inflammatory response via down-regulated the expression levels of inflammatory factors, tumor necrosis factor-alpha and interleukin-6., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Pancreaticoduodenectomy is the standard treatment for resectable periampullary cancer. Surgical site infections (SSI) are common complications with increased morbidity. The study aimed to describe the prevalence, risk factors, microbiology, and outcomes of SSI among patients undergoing pancreaticoduodenectomy., Methods: We conducted a retrospective study in a referral cancer center between January 2015 and June 2021. We analyzed baseline patient characteristics and SSI occurrence. Culture results and susceptibility patterns were described. Multivariate logistic regression was used to determine risk factors, proportional hazards model to evaluate mortality, and Kaplan-Meier analysis to assess long-term survival., Results: A total of 219 patients were enrolled in the study; 101 (46%) developed SSI. Independent factors for SSI were diabetes mellitus, preoperative albumin level, biliary drainage, biliary prostheses, and clinically relevant postoperative pancreatic fistula. The main pathogens were Enterobacteria and Enterococci. Multidrug-resistance rate in SSI was high but not associated with increased mortality. Infected patients had higher odds of sepsis, longer hospital stay and intensive care unit stay, and readmission rate. Neither 30-day mortality nor long-term survival was significantly different between infected and non-infected patients., Conclusions: SSI prevalence among patients undergoing pancreaticoduodenectomy was high and largely caused by resistant microorganisms. Most risk factors were related to preoperative instrumentation of the biliary tree. SSI was associated with greater risk of unfavorable outcomes; however, survival was unaffected., (Copyright © 2023 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

Power circuit breakers (CBs) are vital for the control and protection of power systems, yet diagnosing their faults accurately remains a challenge due to the diversity of fault types and the complexity of their structures. Traditional data-driven methods, although effective, require extensive labeled data for each fault class, limiting their applicability in real-world scenarios where many faults are unseen. This paper addresses these limitations by introducing symptom description transfer-based zero-shot fault diagnosis (SDT-ZSFD), a method that leverages zero-shot learning for fault diagnosis. Our approach constructs a fault symptom description (FSD) framework, which embeds a fault symptom layer between the feature layer and the label layer to facilitate knowledge transfer from seen to unseen fault classes. The method utilizes current and acceleration signals collected during CB operation to extract features. By applying sparse principal component analysis to these signals, we derive high-quality features that are mapped to the FSD framework, enabling effective zero-shot learning. Our method achieves a satisfactory recognition rate by accurately diagnosing unseen faults based on these symptoms. This approach not only overcomes the data scarcity problem but also holds potential for practical applications in power system maintenance. The SDT-ZSFD method offers a reliable solution for CB fault diagnosis and provides a foundation for future improvements in symptom-based zero-shot diagnostic mechanisms and algorithmic robustness., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 ISA. Published by Elsevier Ltd. All rights reserved.)

Cryptochromes (CRYs) are blue light (BL) photoreceptors to regulate a variety of physiological processes including DNA double-strand break (DSB) repair. SUPPRESSOR OF GAMMA RADIATION 1 (SOG1) acts as the central transcription factor of DNA damage response (DDR) to induce the transcription of downstream genes, including DSB repair-related genes BRCA1 and RAD51. Whether CRYs regulate DSB repair by directly modulating SOG1 is unknown. Here, we demonstrate that CRYs physically interact with SOG1. Disruption of CRYs and SOG1 leads to increased sensitivity to DSBs and reduced DSB repair-related genes' expression under BL. Moreover, we found that CRY1 enhances SOG1's transcription activation of DSB repair-related gene BRCA1. These results suggest that the mechanism by which CRYs promote DSB repair involves positive regulation of SOG1's transcription of its target genes, which is likely mediated by CRYs-SOG1 interaction., Competing Interests: Declaration of competing interest The authors declare that we have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Antiviral drugs are widely used, yet their potential risks during early development, particularly within the central nervous system, remain contentious. Oseltamivir phosphate (OSE), a commonly prescribed antiviral, is increasingly detected in various environments. However, its toxicity to organisms and the underlying mechanisms are not well understood. In this study, we employed the zebrafish model to evaluate the developmental neurotoxic effects of OSE at environmentally and therapeutically relevant doses, through high-throughput behavioral analysis, in vivo two-photon imaging, transcriptomic sequencing, pharmacological intervention, and biochemical and molecular assays. Our results indicated that OSE exposure increased heart rate and induced pericardial edema in zebrafish larvae. Additionally, OSE-exposed larvae exhibited hyperactive behavior, impaired social interactions, and reduced habitual learning capacity. Although OSE at our selected levels did not significantly affect neuron count in the brain, it activated neuroinflammatory responses, altered blood vessel morphology, modulated neurotransmitter levels and the expression of neurodevelopment-related genes. Transcriptomic analysis revealed upregulation of mitochondria-related genes associated with oxidative phosphorylation. Further assessments of mitochondrial function demonstrated altered activities of respiratory chain complexes, reduced mitochondrial membrane potential (MMP), and decreased ATP content. Notably, co-treatment with mitochondrial protectants acetyl-l-carnitine-hydrochloride (ALC) or nicotinamide riboside (NR) effectively mitigated OSE-induced neurobehavioral disorders. These findings suggest that overuse of OSE can pose neurodevelopmental risks for both humans and animals, potentially attributable to mitochondrial dysfunction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: The objective of this study was to examine the potential of USP7 as a target for senolytic therapy and to investigate the molecular mechanism by which its inhibitor selectively induced apoptosis in senescent HDF and enhanced DFU wound healing., Methods: Clinical samples of DFU were collected to detect the expression of USP7 and aging-related proteins using immunohistochemistry and Western blot. In addition, β-galactosidase staining, qPCR, flow cytometry, ROS and MMP kits, and Western blot were used to analyze the biological functions of P5091 on senescence, cycle, and apoptosis. RNAseq was employed to further analyze the molecular mechanism of P5091. Finally, the DFU rat model was established to evaluate the effect of P5091 on wound healing., Results: The expression of USP7 and p21 were increased in DFU clinical samples. After treatment with d-glucose (30 mM, 7 days), β-galactosidase staining was deepened, proliferation rate decreased. USP7 inhibitors (P5091) could reduce the release of SASP factors, activate the production of ROS, and reduce MMP. In addition, it induced apoptosis and selectively clears senescent cells through the p53 signaling pathway. Finally, P5091 can improve diabetic wound healing in rats., Conclusion: This study clarified the molecular mechanism of USP7 inhibitor (P5091) selectively inducing apoptosis of high glucose senescent HDF cells. This provides a new senolytics target and experimental basis for promoting DFU wound healing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Interactions between positively charged amino-modified (APS) and negatively charged bare (BPS) polystyrene nanoplastics may cause heteroaggregation in aquatic environments. This study investigated the effects of particle concentration ratio, solution chemistry [electrolytes, pH, and natural organic matter (NOM)], and interaction sequence on their heteroaggregation kinetics. In the absence of electrolytes and NOM, the APS/BPS ratio for attaining maximum heteroaggregation rate (k hetero ) increased from APS/BPS= 3/7 to APS/BPS= 1/1 as pH increased from 4 to 10, indicating that electrostatic interactions dominated heteroaggregation. In the absence of NOM, k hetero ranked APS/BPS= 2/3 > APS/BPS= 1/1 > APS/BPS= 3/2. Colloidal stability decreased linearly as pH increased from 4 to 8 at APS/BPS= 1/1, while diffusion-limited heteroaggregation persisted at pH 10. In NaCl solution, humic acid (HA) retarded heteroaggregation more effectively than sodium alginate (SA) via steric hindrance and weakening electrostatic interactions, following the modified Derjaguin-Landau-Verwey-Overbeek (MDLVO) theory. Compared with simultaneous interactions among APS, BPS, NaCl, and NOM, the NOM retardation effects on heteroaggregation weakened if delaying its interaction with others. In CaCl 2 solution, the effects of NOM on heteroaggregation depended on counterbalance among charge screening, steric hindrance, and calcium bridging. These findings highlight the important role of heteroaggregation between oppositely charged nanoplastics on their fate and transport in aquatic environments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Plant fiber-reinforced polylactic acid (PLA) composites are extensively utilized in eco-friendly packaging, sports equipment, and various other applications due to their environmental benefits and cost-effectiveness. However, PLA suffers from brittleness and poor toughness, which restricts its use in scenarios demanding high toughness. To expand the application range of plant fiber-reinforced PLA-based composites and enhance their poor toughness, this study employed a two-step process involving wheat straw fiber (WF) to improve the interfacial compatibility between WF and PLA. Additionally, four elastomeric materials-poly (butylene adipate-co-terephthalate) (PBAT), poly (butylene succinate) (PBS), polycaprolactone (PCL), and polyhydroxyalkanoate (PHA)-were incorporated to achieve a mutual reactive interface enhancement and elastomeric toughening. The results demonstrated that Fe 3+ /TsWF/PLA/PBS exhibited a tensile strength, elongation at break, and impact strength of 34.01 MPa, 14.23 %, and 16.2 kJ/m 2 , respectively. These values represented a 2.4 %, 86.7 %, and 119 % increase compared to the unmodified composites. Scanning electron microscopy analysis revealed no fiber exposure in the cross-section, indicating excellent interfacial compatibility. Furthermore, X-ray diffraction and differential scanning calorimetry tests confirmed improvements in the crystalline properties of the composites. This work introduces a novel approach for preparing fiber-reinforced PLA-based composites with exceptional toughness and strength., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Most of follicles undergo a degenerative process called follicular atresia. This process directly affects the egg production of laying hens and is regulated by external and internal factors. External factors primarily include nutrition and environmental factors. In follicular atresia, internal factors are predominantly regulated at 3 levels; organic, cellular and molecular levels. At the organic level, the hypothalamic-pituitary-ovary (HPO) axis plays an essential role in controlling follicular development. At the cellular level, gonadotropins and cytokines, as well as estrogens, bind to their receptors and activate different signaling pathways, thereby suppressing follicular atresia. By contrast, oxidative stress induces follicular atresia by increasing ROS levels. At the molecular level, granulosa cell (GC) apoptosis is not the only factor triggering follicular atresia. Autophagy is also known to give rise to atresia. Epigenetics also plays a pivotal role in regulating gene expression in processes that seem to be related to follicular atresia, such as apoptosis, autophagy, proliferation, and steroidogenesis. Among these processes, the miRNA regulation mechanism is well-studied. The current review focuses on factors that regulate follicular atresia at organic, cellular and molecular levels and evaluates the interaction network among these levels. Additionally, this review summarizes atretic follicle characteristics, in vitro modeling methods, and factors preventing follicular atresia in laying hens., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Few studies have explored the mental health status of parents of children with burns and the moderating effect of social support on them., Methods: A survey was performed with parents of 112 burn-injured children at a burn center in China. Their perceived stress, anxiety, depression, sleep quality, and social support were measured by the Chinese Perceived Stress Scale, Hospital Anxiety and Depression Scale, Pittsburgh Sleep Quality Index, and Perceived Social Support Scale., Results: ➀ The prevalence of anxiety (46.43%), depression (52.67%) and poor sleep quality (43.75%) of parents indicated that they experienced emotional and sleep disorders;➁ The perceived stress was positively correlated with sleep quality, anxiety and depression（P＜0.01), and negatively correlated with perceived social support (p＜0.05); ➂ Social support had a significant moderating effect on their perceived stress and anxiety, depression, but not on their sleep quality. With high social support, parental perceived stress had a significant positive association on anxiety and depression, while with low perceived social support, parental perceived stress had no significant association on anxiety and depression., Conclusion: Parents of burned children had increased stress, obvious symptoms of anxiety and depression, and poor sleep quality. Social support had a significant buffering effect on them under low pressure, and high pressure will hinder the buffering effect of social support on stress. Therefore, the ideal services to improve mental health should be provided for them to face different levels of stress., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Ltd and International Society of Burns Injuries. All rights reserved.)

Cryptochromes (CRYs) act as blue light photoreceptors to regulate various plant physiological processes including photomorphogenesis and repair of DNA double strand breaks (DSBs). ADA2b is a conserved transcription co-activator that is involved in multiple plant developmental processes. It is known that ADA2b interacts with CRYs to mediate blue light-promoted DSBs repair. Whether ADA2b may participate in CRYs-mediated photomorphogenesis is unknown. Here we show that ADA2b acts to inhibit hypocotyl elongation and hypocotyl cell elongation in blue light. We found that the SWIRM domain-containing C-terminus mediates the blue light-dependent interaction of ADA2b with CRYs in blue light. Moreover, ADA2b and CRYs act to co-regulate the expression of hypocotyl elongation-related genes in blue light. Based on previous studies and these results, we propose that ADA2b plays dual functions in blue light-mediated DNA damage repair and photomorphogenesis., Competing Interests: Declaration of competing interest The authors declare that we have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Neoadjuvant chemotherapy has variable efficacy in patients with non-small-cell lung cancer (NSCLC), yet reliable noninvasive predictive markers are lacking. This study aimed to develop a radiomics model predicting pathological complete response and postneoadjuvant chemotherapy survival in NSCLC., Materials and Methods: Retrospective data collection involved 130 patients with NSCLC who underwent neoadjuvant chemotherapy and surgery. Patients were randomly divided into training and independent testing sets. Nine radiomics features from prechemotherapy computed tomography (CT) images were extracted from intratumoral and peritumoral regions. An auto-encoder model was constructed, and its performance was evaluated. X-tile software classified patients into high and low-risk groups based on their predicted probabilities. survival of patients in different risk groups and the role of postoperative adjuvant chemotherapy were examined., Results: The model demonstrated area under the receiver operating characteristic (ROC) curve of 0.874 (training set) and 0.876 (testing set). The larger the area under curve (AUC), the better the model performance. Calibration curve and decision curve analysis indicated excellent model calibration (Hosmer-Lemeshow test, P = .763, the higher the P-value, the better the model fit) and potential clinical applicability. Survival analysis revealed significant differences in overall survival (P = .011) and disease-free survival (P = .017) between different risk groups. Adjuvant chemotherapy significantly improved survival in the low-risk group (P = .041) but not high-risk group (P = 0.56)., Conclusion: This study represents the first successful prediction of pathological complete response achievement after neoadjuvant chemotherapy for NSCLC, as well as the patients' survival, utilizing intratumoral and peritumoral radiomics features., (Copyright © 2024. Published by Elsevier Inc.)

Background: To explore the ability of three-dimensional texture analyses based on gray-level run-length matrix (GLRLM) for examining the spatial distribution of pixel values on magnetic resonance imaging (MRI) relaxation time maps and detecting the compositional variation of cartilage repair following treatment with allogeneic human adipose-derived mesenchymal progenitor cells (haMPCs)., Methods: Participants with knee osteoarthritis were randomly divided into three groups with intra-articular haMPCs injections: low-, medium-, and high-dose groups. We analyzed five GLRLM parameters in the T1rho, T2 and T2star maps, including run length non-uniformity (RLNonUni), gray-level non-uniformity (GLevNonU), long run emphasis (LngREmph), short run emphasis (ShrtREmp), and fraction of images in runs. We used the relative D values (the ratio of difference values to baseline) as the objective to avoid errors caused by individual differences. We calculated the two-tailed Pearson's linear correlation coefficient (r) to investigate the correlations of the texture parameters with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores., Results: Compared with the base time, significant reduction of WOMAC score was observed in both high and medium doses groups at terminal time, indicating relief of pain symptoms in high and medium groups with the treatment of allogeneic haMPCs. Significant differences were observed in the GLRLM parameters of cartilage MR relaxation time maps in different doses groups. In both T1rho and T2 relaxation time maps, the high-dose group showed significant increases in relative D values of RLNonUni, GLevNonU, LngREmph and ShrtREmp, which indicated significant changes in the uniformity of relaxation time maps. For T2star map, GLRLM parameters such as GLevNonU and ShrtREmp, especially LngREmph, showed significant increases in relative D values in high-dose group. Among all GLRLM features, LngREmph of three relaxation time maps had performed excellent linear correlations with WOMAC scores., Conclusions: Texture analysis of the cartilage may allow the detection of compositional variation in cartilage repair with the treatment of allogeneic haMPCs. This technique displays potential applications in understanding the mechanism of stem cell repair of the cartilage and assessing the treatment response., Competing Interests: Declaration of competing interest All authors have completed the declaration of interest form. The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cadmium (Cd) exposure is considered as non-infectious stressor to human and animal health. Recent studies suggest that the immunotoxicity of low dose Cd is not directly apparent, but disrupts the immune responses when infected with some bacteria or virus. But how Cd alters the adaptive immunity organ and cells remains unclear. In this study, we applied lipopolysaccharide (LPS, infectious stressor) to induced inflammation in spleen tissues and T cells, and investigated the effects after Cd exposure and the underlying mechanism. Cd exposure promoted LPS-induced the expressions of the inflammatory factors, induced abnormal initiation of autophagy, but blocked autophagic flux. The effects Cd exposure under LPS activation were reversed by the autophagy promoter Rapamycin. Under LPS activation conditions, Cd also induced oxidative stress by increasing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and reducing total antioxidant capacity (T-AOC) activity. The increased superoxide dismutase (SOD) activity after Cd exposure might be a negative feedback or passive adaptive regulation of oxidative stress. Cd-increased autophagic flux inhibition and TNF-α expression were reversed by ROS scavenger α-tocopherol (TCP). Furthermore, under LPS activation condition, Cd promoted activation of toll-like receptor 4 (TLR4)/IκBα/NFκ-B signaling pathway and increased TLR4 protein stability, which were abolished by the pretreatment of Rapamycin. The present study confirmed that, by increasing ROS-mediated inhibiting autophagic degradation of TLR4, Cd promoted LPS-induced inflammation in spleen T cells. This study identified the mechanism of autophagy in Cd-aggravated immunotoxicity under infectious stress, which could arouse public attention to synergistic toxicity of Cd and bacterial or virus infection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Utilizing alkaline solid wastes, such as steel slag, as substrates in tidal flow constructed wetlands (TFCWs) can effectively neutralize the acidity generated by nitrification. However, the impacts of steel slag on microbial communities and the potential risk of heavy metal release remain poorly understood. To address these knowledge gaps, this study compared the performance and microbial community structure of TFCWs filled with a mixture of steel slag and zeolite (TFCW-S) to those filled with zeolite alone (TFCW-Z). TFCW-S exhibited a much higher NH 4 + -N removal efficiency (98.35 %) than TFCW-Z (55.26 %). Additionally, TFCW-S also achieved better TN and TP removal. The steel slag addition helped maintain the TFCW-S effluent pH at around 7.5, while the TFCW-Z effluent pH varied from 3.74 to 6.25. The nitrification and denitrification intensities in TFCW-S substrates were significantly higher than those in TFCW-Z, consistent with the observed removal performance. Moreover, steel slag did not cause excessive heavy metal release, as the effluent concentrations were below the standard limits. Microbial community analysis revealed that ammonia-oxidizing bacteria, ammonia-oxidizing archaea, and complete ammonia-oxidizing bacteria coexisted in both TFCWs, albeit with different compositions. Furthermore, the enrichment of heterotrophic nitrification-aerobic denitrification bacteria in TFCW-S likely contributed to the high NH 4 + -N removal. In summary, these findings demonstrate that the combined use of steel slag and zeolite in TFCWs creates favorable pH conditions for ammonia-oxidizing microorganisms, leading to efficient ammonia removal in an environmentally friendly manner., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

China is the largest industrial and pharmaceutical country in the world. The pharmaceutical industry, being a highly polluting sector, is the primary target of environmental regulation in the industry. The rapid development of pharmaceutical industry has posed a severe challenge to the environmental protection strategy of "carbon reduction and carbon neutrality" and the goal of "synergizing the reduction of pollution and carbon emissions" in China's "14th Five-Year Plan". Therefore, this paper starts from the whole industry, takes the life cycle of the whole production process of the pharmaceutical industry as the guidance, and selects a pharmaceutical company in Tianjin as the research object. Then using Life Cycle Assessment (LCA) to Characterization, Standardization, and Weighting the environmental impact of the waste gas treatment process before and after improvement based on waste gas emission characteristics from the pharmaceutical factory. LCA results show that GWP and AP are the most important environmental impact types, which account for >85 % of the total characterization value. I and II - Chemical Pharmaceutical Stage is the critical life cycle stage, accounting for over 80 % of the total characteristic values. This research proposes emission reduction countermeasures based on LCA results and simulates Emission reduction scenarios and economic evolution. If effectively implementing emission reduction countermeasures, reducing the environmental characterization value by 80 to 90 %, and generating economic benefit of 2.66 × 10 8 RMB/year. This research could guide improvement plans and emission reduction countermeasures of waste gas treatment in the pharmaceutical industry, which realizes collaborative management about efficient reduction of pollution and carbon and generates significant environmental, technological, economic, and social benefits., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Emerging and potential influenza pandemics still are an enormous worldwide public health challenge. The PA N endonuclease has been proved to be a promising target for anti-influenza drug design. Here, we report the discovery and optimization of potent Y-shaped PA N inhibitors featuring multi-site binding characteristics with l-DOPA as a starting point. We systematically modified the hit 1 bearing two-binding characteristics based on structure-based rational design combined with multisite binding and conformational constraint strategies, generating four families of l-DOPA derivatives for SARs analysis. Among these substances, N, 3-di-substituted 1, 2, 3, 4-tetrahydroisoquinoline derivative T-31 displayed superior properties as a lead PA N endonuclease inhibitor and antiviral agent. The lead T-31 inhibited PA N endonuclease activity with an IC 50 value of 0.15 μM and showed broad and submicromolar anti-influenza potency in cell-based assays. More importantly, T-31 could simultaneously target both influenza HA and the RdRp complex, thus interfering with virus entry into host cells and viral replication. This study offers a set of novel PA N endonuclease inhibitors with multi-site binding characteristics starting from the l-DOPA skeleton., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Applying selenium (Se) fertilizer is the only way to alleviate soil Se deficiency. Although effects of nanoselenium foliar application on plant growth and stress resistance have been extensively investigated, soil application of nanoselenium on soil microorganisms and their relationship with crop quality and soil health remains unclear. In this study, a steady-state homogeneous nanoparticle of epigallocatechin gallate Se (ESe) was synthesized, and a pot experiment was conducted applying ESe at five concentrations (0, 1, 10, 50, and 100 mg kg -1 ) to the tea planattion soil. The study revealed a significant increase in Se concentration in soil and tea with ESe application and identified 2.43-7.8 mg kg -1 as the safe and optimal range for soil application. Specifically, the moderate dose of ESe improved the tea quality [reduced tea polyphenols (TP), increased free amino acids (AA), and reduced TP/AA] and soil quality index (SQI). Besides, in marure tea leaves, antioxidant enzyme activities [promote catalase (CAT) superoxide dismutase (SOD), and peroxidase (POD)] increased, while level of oxidative stress [malondialdehyde (MDA), hydrogen peroxide (H 2 O 2 ) and superoxide anion (O 2 - )] decreased with ESe application. The 16S rRNA of the soil bacteria showed that ESe application significantly changed the community structure of soil bacteria but did not alter the diversity of the bacteria and the abundance of dominant taxa (phylum and genus levels). Statistical analysis of the taxonomic and functional profiles (STAMP) detected 21 differential taxa (genus level), mainly low-abundance ones, under the ESe application. Linear regression and random forest (RF) modeling revealed that the low-abundance bacterial taxa were significantly correlated with SQI (R 2  = 0.28, p < 0.01) and tea quality (R 2  = 0.23-0.37, p < 0.01). Thus, the study's findings suggest that ESe application affects soil and tea quality by modulating the low-abundance taxa in soil. The study also highlights the crucial role of low-abundance bacterial taxa of the rhizosphere in regulating soil functions under the ESe application., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The gut microbiota is closely related to liver diseases. The dietary pattern associated with sulfur-metabolizing bacteria in stool has been found to influence intestinal health., Objective: We aimed to investigate whether consuming the sulfur microbial diet is associated with nonalcoholic fatty liver disease (NAFLD)., Methods: We included 143,918 participants of European descent from the UK Biobank. Information on serving sizes used per diet component was recorded by an online 24-h dietary assessment tool (Oxford WebQ). The total sulfur microbial diet score was constructed by summing the product of β-coefficients and corresponding serving sizes. NAFLD was ascertained using hospital inpatient and death records. Cox proportional hazard models were used to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI). Mediation analyses were used to investigate underlying mediators including body mass index, waist circumference, glucose, triglyceride, urate, and C-reactive protein. A polygenic risk score for NAFLD was constructed and stratified to assess whether the association is modified by genetic predisposition., Results: After a median follow-up of 11.7 y (interquartile range: 11.3-12.5 y), we documented 1540 incident cases of NAFLD. After adjustment for covariates, we observed an overall J-shaped relationship between the sulfur microbial diet and risk of NAFLD. Those in the highest quartile of sulfur microbial diet score had a 46% increased risk of NAFLD [HR Q4vsQ1 (95% CI): 1.46 (1.26, 1.69)]. We also found that this association is partly mediated by metabolic disorders and systemic inflammation. In addition, the positive association was stronger among individuals at higher genetic risk for NAFLD (P interaction = 0.044)., Conclusions: The sulfur microbial diet had adverse associations with incident NAFLD, particularly in those at a higher genetic risk. Our study may provide evidence on the role of sulfur-metabolizing bacteria in the diet-NAFLD association., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Eight nitrogenous compounds including five undescribed ones, aeswilnitrousol A (1), aeswilnitrousosides BD (2-4), and 6-(2-hydroxy-3-methylbutylamino)-8-oxoadenine (5) were isolated from the seeds of Aesculus wilsonii. Their structures and absolute configurations were established based on spectroscopic determination, calculated electronic circular dichroism (ECD) analysis, as well as chemical reaction methods. Among the three known compounds, 7 and 8 were obtained from the Aesculus genus for the first time, and 6 was gained from this plant initially. The 13 C NMR data of 7 and 8 were reported for the first time. Moreover, the inhibitory effect of all the isolates against LPS-induced nitric oxide production in RAW264.7 macrophages was evaluated. As a result, compounds 2 and 8 exhibited anti-inflammatory activity in a concentration-dependent manner at 10, 25, and 50 μM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The enhanced effects of formaldehyde biodegradation in a biofilm packing tower are investigated in this study. Three experimental groups were established: a blank control group, a biochar addition group, and a lanthanum addition group. The inlet gas flow rate, the inlet gas concentration, and the structural succession characteristics of the microbial community in the tower were investigated by regular sampling. The intracellular metabolites and key enzymes of the dominant functional bacteria, Pseudomonas P1 and Methylobacterium Q1, in the tower were analyzed. The results indicated that with the biochar addition, the formaldehyde purification efficiency increased significantly from 91.67-94.67 % to 94.12 96.85 %, and the bio-elimination capacity increased with an increase in the inlet gas flow rate from 2.314 to 13.988 mg L -1 h -1 to 2.697-15.051 mg L -1 h -1 . With the addition of lanthanum, the purification efficiency increased significantly from 90.80-93.98 % to 94.36-96.78 %, and the bio-elimination capacity increased with an increase in the inlet gas concentration from 1.099-11.284 mg L -1 h -1 to 1.266-11.961 mg L -1 h -1 . The microbial community structure in the tower changed with system operation, and the formaldehyde degrading functional bacteria formed the dominant bacteria. It was verified that P1 and Q1 metabolized high concentrations of formaldehyde by the serine cycle and the ribulose monophosphate (RuMP) cycle., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jie Wang reports financial support was provided by National Natural Science Foundation of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Twenty-four aromatic compounds including five novel ones, dolilabphenosides A (1), B 1 (2), B 2 (3), C 1 (4), and C 2 (5) were obtained from the seeds of Dolichos lablab L. Their structures were established based on spectroscopic analyses and chemical reactions. Among the known compounds, 9, 10, 14, 17, 19, and 22-24 were gained from the family Leguminosae for the first time, and 6, 8, 11-13, 15, 16, 18, 20, as well as 21 were firstly identified from Dolichos genus. Moreover, the inhibitory effect evaluation of all the isolates against LPS-induced nitric oxide (NO) production in RAW264.7 macrophages suggested that compounds 1-3, 6, 7, 11-15, 17, 20, 21, 23, 24 exhibited anti-inflammatory activity in a concentration-dependent manner. Moreover, the novel compounds, dolilabphenosides A (1), B 1 (2), B 2 (3) were found to inhibit the secretion of inflammatory cytokine IL-1β., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Understanding soil organic carbon (SOC), the largest carbon (C) pool of a terrestrial ecosystem, is essential for mitigating climate change. Currently, the spatial patterns and drivers of SOC in the plantations of tea, a perennial leaf crop, remain unclear. Therefore, the present study surveyed SOC across the main tea-producing areas of China, which is the largest tea producer in the world. We analyzed the soil samples from tea plantations under different scenarios, such as provinces, regions [southwest China (SW), south China (SC), south Yangtze (SY), and north Yangtze (NY)], climatic zones (temperate, subtropical, and tropical), and cultivars [large-leaf (LL) and middle or small-leaf (ML) cultivars]. Preliminary analysis revealed that most tea-producing areas (45%) had SOC content ranging from 10 to 20 g kg -1 . The highest SOC was recorded for Yunnan among the various provinces, the SW tea-producing area among the four regions, the tropical region among the different climatic zones, and the areas with LL cultivars compared to those with ML cultivars. Further Pearson correlation analysis demonstrated significant associations between SOC and soil variables and random forest modeling (RF) identified that total nitrogen (TN) and available aluminum [Ava(Al)] of soil explained the maximum differences in SOC. Besides, a large indirect effect of geography (latitude and altitude) on SOC was detected through partial least squares path modeling (PLS-PM) analysis. Thus, the study revealed a high spatial heterogeneity in SOC across the major tea-producing areas of China. The findings also serve as a basis for planning fertilization strategies and C sequestration policies for tea plantations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

In vitro cytotoxicity-guided isolation based on a MTT assay was conducted for Penthorum chinense Pursh. (Penthoraceae). In the active components (EtOAc extract of P. chinense), eight undescribed neolignans, penthoneolignans A-H (1-8), and two known analogs (9 and 10) were obtained and identified. Their absolute configurations were determined by experimental and computational comparison of electronic circular dichroism spectra analysis. The MTT experiment results of the obtained neolignans on HT29 and LoVo cells indicated previously undescribed neolignans, penthoneolignans A (1) and F (6), showed better cytotoxicity than the positive drug 5-fluorouracil. Then, functional technologies such as the 5-ethyny1-2'-deoxyridine, wound healing, Transwell, and Western blot assays indicated that they could significantly inhibit the proliferation of HT29 and Lovo cells, promote apoptosis by up-regulating Bax, and down-regulating B-cell CLL/lymphoma 2 and poly ADP-ribose polymerase. Furthermore, a Western blot assay combining the Dsh homolog 2 agonist IWP-L6 and the β-catenin agonist MG132 suggested their mechanism of action was closely related to the inhibition of the Wnt/β-catenin signaling pathway. In conclusion, previously undescribed neolignans, penthoneolignans A (1) and F (6), may intervene in the development and progression of colorectal cancer by inhibiting the Wnt/β-catenin signaling pathway and have the potential to be drug candidates., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Porcine epidemic diarrhoea (PED) caused by the porcine epidemic diarrhoea virus (PEDV) is the most devastating disease in the global pig industry due to its high mortality rate in piglets. The host factors critical for PEDV replication are poorly understood. Here, we designed a pooled African green monkey genome-scale CRISPR/Cas9 knockout (VeroCKO) library containing 75,608 single guide RNAs targeting 18,993 protein-coding genes. Subsequently, we use the VeroCKO library to identify key host factors facilitating PEDV infection in Vero E6 cells. Several previously unreported genes associated with PEDV infection are highly enriched post-PEDV selection. We discovered that knocking out the tripartite motif 2 (TRIM2) and the solute carrier family 35 member A1 (SLC35A1) inhibited PEDV replication. Virtual screening and molecular docking approaches showed that chem-80,048,685 (M2) s ignificantly inhibited PEDV attachment and late replication by impeding SLC35A1. Furthermore, we found that knocking out SLC35A1 in Vero E6 cells upregulated a disintegrin and metalloprotease protein-17 (ADAM17) by splicing porcine aminopeptidase N (pAPN) and angiotensin-converting enzyme 2 (ACE2) ectodomains to reduce PEDV-infection in a CMP-Sialic Acid (CMP-SA) cell entry-independent manner. These findings provide a new perspective for a better understanding of host-pathogen interactions and new therapeutic targets for PEDV infection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Trichloroethylene (TCE) was a widely used industrial solvent, and now has become a major environmental pollutant. Exposure to TCE has been found to result in significant damage to the liver, leading to hepatic toxicity. In our previous study, we discovered that a histone chaperon called SET plays a crucial role in mediating the DNA damage and apoptosis caused by TCE in hepatic cells. However, the precise function of SET in the response to DNA damage is still not fully understood. In this study, we evaluated TCE-induced DNA damage of hepatic L-02 cells with SET-knockdown, then analyzed alterations of H3K79me3 and p53 in hepatic cells and carcinogenic mice livers. Results suggested that SET interferes with DNA response via mediating down-regulation of p53 and partially suppressing H3K79me3 under treatment of TCE. To further verify the regulatory cascade, H3K79me3 was reduced and p53 was knocked down in L-02 cells respectively, and extent of DNA damage was evaluated. Reduced H3K79me3 was found leading to down-regulation of p53 which further exacerbated TCE-induced DNA injury. These findings demonstrated that SET-H3K79me3-p53 served as an epigenetic regulatory axis involved in TCE-induced DNA damage response., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Polychlorinated biphenyls (PCBs) are a type of persistent organic pollutant (POP). Our previous study demonstrated that exposure to 0.5-50 μg/kg bw PCB138 during postnatal days (PND) 3-21 led to elevated serum uric acid (UA) levels and kidney injury in adult male mice. Given that the prevalence of hyperuricemia (HUA) is significantly lower in women than in men, it is worth investigating whether POP-induced HUA and its secondary kidney injury have sexual dimorphism. Herein, we exposed female mice to 0.5-50 μg/kg bw PCB138 during PND 3-21, resulting in elevated serum UA levels, but without causing significant kidney damage. Concurrently, we found a negative correlation between serum 17β-estradiol (E2) and serum UA levels. We also observed down-regulation of estrogen receptor (ER) protein levels in the kidneys of the PCB138-exposed groups. Furthermore, our study showed that E2 rescued the increased UA level and cytotoxicity caused by HUA in human renal tubular epithelial (HK-2) cells. Collectively, our findings suggest that E2 likely plays a crucial protective role in PCB138-induced HUA and kidney injury in female mice. Our research highlights the existence of sexual dimorphism in kidney injury secondary to HUA induced by POPs, which could provide guidance for individuals of different genders in preventing kidney injury caused by environmental factors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The objective of our study, which combined API-ILs strategy and controlled-release polymers, was to prepare a 72 h long-acting drug-in-adhesive patch for optimum delivery of asenapine (ASE). Special attention was paid to the permeation promotion mechanism and the controlled release behavior of ASE-ILs in pressure sensitive adhesives (PSA). Formulation factors were investigated by ex vivo transdermal experiments. The optimized patch was evaluated by pharmacokinetics study and skin irritation test. The obtained formulation was as follows, 15% w/w ASE-MA (about 1136 μg/cm 2 ASE, 413 μg/cm 2 MA), AACONH 2 (Amide adhesive) as the matrix, 80 μm thickness, backing film of CoTran™ 9733. The optimized patch displayed satisfactory ex vivo and in vivo performance with Q 72 h of 620 ± 44 µg/cm 2 and F abs of 62.4%, which utilization rate (54.6%) was significantly higher than the control group (38.3%). By using the classical shake flask method, 13 C NMR, DSC, and FTIR, the physicochemical properties and structure of ILs were characterized. log D o/w , ATR-FTIR, Raman, and molecular dynamics simulation results confirmed that ASE-MA (MA: 3-Methoxypropionic acid) had appropriate lipophilicity, and affected lipid fluidity as well as the conformation of keratin to improve the skin permeation. The FTIR, MDSC, rheology, and molecular docking results revealed that hydrogen bond (H-bond), were formed between ASE-MA and PSA, and the drug increased the molecular mobility of polymer chains. In summary, the 72 h long-acting patch of ASE was successfully prepared and it supplied a reference for the design of long-acting patches with ASE., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Colorectal cancer (CRC) is one of the three major malignant tumors in the world. The major treatments currently recommended for it are surgery, radiotherapy, and chemotherapy, all of which are frequently accompanied by a poor prognosis and high recurrence rate. To limit cell proliferation and metastasis, trigger cell apoptosis, and regulate tumor microenvironment (TME), researchers are focusing attention on investigating highly effective and non-toxic natural medicines. According to the research reported in 89 pieces of related literature, between 2018 and 2021, specialists extracted 48 different types of polysaccharides with CRC inhibitory actions from various plants, including Dendrobium officinale Kimura et Migo., Nostoc commune Vaucher, and Ganoderma lucidum (Leyss. ex Fr.) Karst. The novel founded mechanisms mainly include: inhibiting cancer cell proliferation by acting on IRS1/PI3K/Akt and IL-6/STAT3 pathways; inducing cancer cell apoptosis by acting on LncRNA HOTAIR/Akt mediated-intrinsic apoptosis, or regulating the TNF-α-mediated extrinsic apoptosis; inducing cancer cell autophagy by acting on endoplasmic reticulum stress or mTOR-TFEB pathway; inhibiting cancer cell metastasis by regulating Smad2/3 and TLR4/JNK pathways; regulating TME in CRC; and maintaining the intestinal barrier. This review will provide more novel research strategies and a solid literature basis for the application of polysaccharides in the treatment of CRC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Accumulated clinical and biomedical evidence suggests that abnormalities in systemic metabolic processes such as fatty acid and amino acid metabolism can affect the brain function and behavior of various central nervous system diseases such as Alzheimer's disease (AD). In this study, metabolic profiling was used to investigate changes in plasma and urine metabolites following stereotactic injection of amyloid β (Aβ) and treatment with donepezil in rats. Aβ causes cognitive impairment, while donepezil treatment successfully improves memory impairment. Donepezil improves Aβ-induced plasma fatty acid and bile acid metabolism disorders, as well as Aβ-induced urine phenylalanine and tryptophan metabolism disorders in rats. More specifically, the plasma fatty acids improved by donepezil include alpha-linolenic acid, stearidonic acid, eicosapentaenoic acid, docosahexaenoic acid, linoleic acid, arachidonic acid, oleic acid, and palmitic acid, among others. Additionally, donepezil significantly restored the downregulation of bile acids such as ursodeoxycholic acid, cholic acid, and glycocholic acid caused by Aβ. As for urine metabolites, phenylacetylglycine, epinephrine, and other phenylalanine metabolites, as well as kynurenic acid, xanthurenic acid, and other tryptophan metabolites, were worsened by Aβ and improved by donepezil. These findings suggest that the cognitive impairment induced by Aβ and the improvement by donepezil are associated with changes in metabolic disorders in rats. This study provides basic data for the effects of Aβ and donepezil on plasma and urine metabolites in Aβ-induced AD rat models., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Peripheral T-cell lymphomas (PTCL) with T-follicular helper phenotype (PTCL-TFH) has recurrent mutations affecting epigenetic regulators, which may contribute to aberrant DNA methylation and chemoresistance. This phase 2 study evaluated oral azacitidine (CC-486) plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) as initial treatment for PTCL. CC-486 at 300 mg daily was administered for 7 days before C1 of CHOP, and for 14 days before CHOP C2-6. The primary end point was end-of-treatment complete response (CR). Secondary end points included safety and survival. Correlative studies assessed mutations, gene expression, and methylation in tumor samples. Grade 3 to 4 hematologic toxicities were mostly neutropenia (71%), with febrile neutropenia uncommon (14%). Nonhematologic toxicities included fatigue (14%) and gastrointestinal symptoms (5%). In 20 evaluable patients, CR was 75%, including 88.2% for PTCL-TFH (n = 17). The 2-year progression-free survival (PFS) was 65.8% for all and 69.2% for PTCL-TFH, whereas 2-year overall survival (OS) was 68.4% for all and 76.1% for PTCL-TFH. The frequencies of the TET2, RHOA, DNMT3A, and IDH2 mutations were 76.5%, 41.1%, 23.5%, and 23.5%, respectively, with TET2 mutations significantly associated with CR (P = .007), favorable PFS (P = .004) and OS (P = .015), and DNMT3A mutations associated with adverse PFS (P = .016). CC-486 priming contributed to the reprograming of the tumor microenvironment by upregulation of genes related to apoptosis (P < .01) and inflammation (P < .01). DNA methylation did not show significant shift. This safe and active regimen is being further evaluated in the ALLIANCE randomized study A051902 in CD30-negative PTCL. This trial was registered at www.clinicaltrials.gov as #NCT03542266., (© 2023 by The American Society of Hematology.)

To further explore short-term exposure of enrofloxacin (ENR) induced toxicity in crucian carp brain that has been reported by our previous work, as well as the possible toxicological mechanisms, this study investigated the blood-brain barrier (BBB) permeability to low dosage of ENR through comprehensively assessing expression of BBB constitutive molecules zonula occludens-1 (ZO-1) and permeability glycoprotein (P-gp), as well as ENR residue in brain of crucian carp. Toxicologic effect of ENR on brain tissue was determined through evaluating expression of brain-derived proteins S100B, neuron specific enolase (NSE) and glial fibrillary acidic protein (GFAP) in crucian carp brain tissue, as well as contents of the proteins in serum. The toxicological mechanisms were explored through analyzing transcriptome analysis data. Results showed that ENR possessed excellent permeability to crucian carp BBB, which was closely related to deranged BBB structure and declined ENR efflux that were attributed to downregulated expression of ZO-1 and P-gp by ENR exposure. Meanwhile, S100B, NSE and GFAP were upregulated in brain by ENR, and came out into blood across the damaged BBB. These data revealed that ENR induced disruption of BBB and damage of brain tissue in crucian carp. Transcriptome analysis data indicated that ENR induced toxicologic effect might be related to modification of metabolism, organismal systems, and genetic information processing, etc., and that PI3K/Akt, MAPK, HIF-1, and ubiquitin mediated proteolysis involved the mechanisms, most of the mechanisms were attributed to ENR induced oxidative stress in crucian carp brain., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)