Search

Fly ash exhibits volcanic ash activity and can be utilized as a cementitious material to reduce filling costs. The limited flow characteristics of mine solid waste filling slurry can impact backfill efficiency. Instead of using a large amount of cement, we employ fly ash as a cementing material to prepare filling slurries with varying air-entraining agent dosages. The results indicate that as the air-entraining agent dosage increases from 0 to 8%, the fluidity of the filling slurry improves, and the strength increases within the first 5 days of curing. The strength of the filling increases initially from 5 to 28 days of curing with the increase in air-entraining agent dosage, reaching a peak at 4% dosage, with an 11.35% higher strength compared to the filling body without the air-entraining agent. The microscopic pore structure and hydration product analysis reveal that introducing an appropriate amount of bubbles results in an even distribution of cementitious material and aggregates, improving fluidity and strength. However, excessive addition of air-entraining agents inhibits the growth of C–S–H and the filling ability of AFt for primary pores, ultimately impacting the long-term strength growth of the filling body.

In recent years, as the infectious diseases caused by pathogens such as novel coronavirus and mpox (formerly called monkeypox) spread globally, the significance of identification, preservation, and sharing of pathogenic resources become prominent. Along with the rapid development of biorepositories, it is imperative to evaluate their operation in a scientific manner. By using the literature review and modified Delphi method, this study develops a benchmarking tool for the comprehensive evaluation of the operation of biorepositories for pathogenic resources. The effective response rates of both rounds of expert surveys were 100 %. The authority coefficients (Cr) were 0.82 and 0.85, respectively, manifesting the reliability of consultation results. In the second-round survey, the Kendall’s coefficient of concordance (Kendall’s W) of all indicators ranged from 0.09 to 0.31 (P

Pullulan (PUL) is a widely used agent for electrospinning. However, nanofibers electrospun solely from PUL exhibit a highly hydrophilic nature and a bead-like structure. In this study, 1–5 wt% citrus pectin (CP) was introduced to construct a hybrid electrospinning system to investigate the effects of CP concentration on the properties of the electrospun nanofibers. The results reveal that the bead-like structure, rigidity, and hydrophobicity of the nanofibers underwent significant improvements following the introduction of CP. Furthermore, to demonstrate the protective effect of the nanofiber on astaxanthin, 0.1 wt% astaxanthin was encapsulated in the hybrid electrospinning system containing 5 wt% CP. The results show that after encapsulating astaxanthin, the rigidity of the nanofiber further increased, with a tensile strength of 12.5 MPa and a break elongation of 2.9 %. Additionally, the nanofiber system demonstrates excellent protection of the antioxidant activity of astaxanthin under UV exposure compared to free astaxanthin.

Regulated cell death (RCD) has been documented to have great potentials for discovering novel biomarkers and therapeutic targets in malignancies. But its role and clinical value in HR+/HER2- breast cancer, the most common subtype of breast cancer, are obscure. In this study, we comprehensively explored 12 types of RCD patterns and found extensive mutations and dysregulations of RCD genes in HR+/HER2- breast cancer. A prognostic RCD scoring system (CDScore) based on six critical genes (LEF1, SLC7A11, SFRP1, IGFBP6, CXCL2, STXBP1) was constructed, in which a high CDScore predicts poor prognosis. The expressions and prognostic value of LEF1 and SFRP1were also validated in our tissue microarrays. The nomogram established basing on CDScore, age and TNM stage performed satisfactory in predicting overall survival, with an area under the ROC curve of 0.89, 0.82 and 0.8 in predicting 1-year, 3-year and 5-year overall survival rates, respectively. Furthermore, CDScore was identified to be correlated with tumor microenvironments and immune checkpoints by excavation of bulk and single-cell sequencing data. Patients in CDScore high group might be resistant to standard chemotherapy and target therapy. Our results underlined the potential effects and importance of RCD in HR+/HER2- breast cancer and provided novel biomarkers and therapeutic targets for HR+/HER2- breast cancer patients.

Background and aims: Tumor recurrence significantly affects the prognostic outcomes for liver cancer patients following liver transplantation. However, existing predictive models often neglect the inclusion of body composition indicators. Hence, this research aimed to investigate the significance of the psoas muscle index (PMI) in evaluating the post-transplant prognosis of liver cancer. Methods: A retrospective analysis was conducted on liver cancer patients who underwent liver transplantation surgery. Imaging analysis was performed using CT data to calculate PMI based on the left and right psoas muscle areas. Subsequently, the patients were categorized into PMI-Low and PMI-High groups using the established cut-off values. Univariate and multivariate analyses were performed using Cox proportional hazards regression to assess the correlation between PMI and clinical outcomes, and a nomogram was constructed accordingly. Results: Among the 225 patients included in the analysis, the PMI-High group exhibited significantly improved overall survival (P

Radish (Raphanus sativus L.) undergoes texture changes in their phy-chemical properties during the long-term dry-salting process. In our study, we found that during the 60-day salting period, the hardness and crispness of radish decreased significantly. In further investigation, we observed that the collaborative action of pectin methylesterase (PME) and polygalacturonase (PG) significantly decreased the total pectin, alkali-soluble pectin (ASP), and chelator-soluble pectin (CSP) content, while increasing the water-soluble pectin (WSP) content. Furthermore, the elevated activities of cellulase and hemicellulase directly led to the notable fragmentation of cellulose and hemicellulose. The above reactions jointly induced the depolymerization and degradation of cell wall polysaccharides, resulting in an enlargement of intercellular spaces and shrinkage of the cell wall, which ultimately led to a reduction in the hardness and crispness of the salted radish. This study provided key insights and guidance for better maintaining textural properties during the dry-salting process of radish.

In order to investigate the effects of different drying methods on the properties of porous starch. The present study used four drying methods, namely hot air drying (HD), spray drying (SPD), vacuum freeze drying (FD) and supercritical carbon dioxide drying (SCD) to prepare maize and kudzu porous starch. Findings indicated that the physicochemical properties (e.g., morphology, crystallinity, enthalpy value, porosity, surface area and water absorption capacity as well as dye absorption capacity, particle size) of porous starch were significantly affected by the drying method. Compared with other samples, SCD-treated porous starch exhibited the highest surface areas of the starch (2.943 and 3.139 m2/g corresponding to kudzu and maize, respectively), amylose content (22.02 % and 16.85 % corresponding to kudzu and maize, respectively), MB and NR absorption capacity (90.63 %, 100.26 % and 90.63 %, 100.26 %, corresponding to kudzu ad maize, respectively), and thermal stability, whereas HD-treated porous starch showed the highest water-absorption capacity (123.8 % and 131.31 % corresponding to kudzu and maize, respectively). The dye absorption of the maize and kudzu porous starch was positively correlated with surface area, according to Pearson's correlation analysis. Therefore, in this study, our aim was to explore the effects of different drying methods on the Structure and properties of porous starch, and provide reference for selecting the best drying method for its application in different fields.

Summary: Purpose: This study aims to explore the expectations and acceptability of a smart nursing home model among Chinese older adults and their family members based on a scoping review that defines the concept of smart nursing homes. Methods: A qualitative case study was employed for this research. Semi-structured, in-depth interviews and focus group discussions were conducted on WeChat. Participants were purposively sampled through snowball sampling in Hainan and Dalian, China. A total of 28 older adults aged 60–75 and six adult children were interviewed until data saturation was achieved, followed by a thematic analysis. Results: The expectations of smart nursing homes include: 1) quality of care supported by governments and societies; 2) smart technology applications; 3) the presence of a skilled healthcare professional team; 4) access to and scope of basic medical services; and 5) integration of medical services. The acceptability of smart nursing homes included factors such as stakeholders’ perceived efficaciousness, usability, and collateral damages of using smart technologies, and the coping process of adoption was influenced by factors such as age, economic status, health status, education, and openness to smart technologies among older adults. Conclusions: Chinese older adults and their family members have a positive perception of the smart nursing home model. The qualitative evidence regarding their expectations and acceptability of smart nursing homes contributes valuable insights for a wide range of stakeholders involved in the planning and implementation of smart nursing homes.

In order to fight the battle for reducing total phosphorus (TP) in Dongting Lake and continuously improve the water ecological environment of the Yangtze River, this study accounts for the TP pollution load in Dongting Lake. To this end, the sources of the pollutants are analyzed and corresponding prevention and control measures are proposed by comprehensive use of field research and historical data analysis. The obtained results reveal that the annual TP input to the Dongting Lake was 23287 t in 2017, among which the input from four rivers and three lake entrances represent the main source with an annual TP input of 14033 t (including 3681 t from sediment input), accounting for 60.26%. Agricultural pollution is the second largest source of TP input, accounting for 32.69%, while domestic pollution only accounts for 5.93%. Additionally, the contributions of atmospheric deposition and industrial pollution in order are 0.69% and 0.4%. The TP input from moving sources such as birds and waterway shipping is very small, only accounting for 0.03%. Based on the achieved results, this study aims to propose corresponding prevention and control measures in four aspects: interception of river and lake pollution, control of agricultural pollution sources, enhancement of sewage treatment and industrial pollution prevention.

The widespread use of biogas slurry could potentially raise the environmental risk of antibiotics. Dissolved organic matter (DOM), as the most active part of biogas slurry, was able to interact with antibiotics and play a crucial role in the structure and function of soil and aquatic ecosystems. The recent shifts in global climate patterns have garnered significant attention due to their substantial impact on temperature, thereby exerting a direct influence on the characteristics of DOM and subsequently on the environmental behavior of antibiotics. However, there is limited research concerning the impact of temperature on the binding of DOM and antibiotics. Thus, this study aimed to explore the temperature-dependent structural transformation and driving factors of biogas slurry-derived DOM (BSDOM). Additionally, the binding characteristics between BSDOM and the commonly used antibiotic norfloxacin (NOR) at different temperatures were studied by using multi spectroscopic methods and two-dimensional correlation spectroscopy (2D-COS) analysis. The results suggested that the temperature-dependent structural transformation of BSDOM was reversible, with a slight lag in the transition temperature under cooling (13 °C for heating and 17 °C for cooling). Heating promoted the conversion of protein-like to humic-like substances while cooling favored the decomposition of humic-like substances. BSDOM and NOR were static quenching, with oxygen-containing functional groups such as C-O and -OH playing an important role. Temperature influenced the order of binding, the activity of the protein fraction, and its associated functional groups. At temperatures of 25 °C and 40 °C, the fluorescent components were observed to exhibit consistent binding preferences, whereby the humic-like component demonstrated a greater affinity for NOR compared to the protein-like component. However, the functional group binding order exhibited an opposite trend. At 10 °C, a new protein-like component appeared and bound preferentially to NOR, when no C-O stretch corresponding to the amide was observed. The finding will contribute to a comprehensive understanding of the interaction mechanisms between DOM and antibiotics under climate change, as well as providing a theoretical basis to reduce the environmental risks of biogas slurry and antibiotics.

Porous starch is a denatured starch product with high porosity, a large specific surface area, and strong adsorption. It is widely used in medicine, food, and chemical industries. Native starch includes types A, B, and C. In this study, the various starch materials, including potato maize, and kudzu starch, were used to prepare different crystal types of porous starch with α-amylase and glucoamylase. The structural and chemical characteristics of the porous starch were measured using Fourier-transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction, and differential scanning calorimetry. The results showed that maize , potato and kudzu starches were typically A, B, and C types, respectively. Compared to the native starch, the three types of porous starch treated with α-amylase and Glucoamylase cause varying degrees of destruction of the surface of the starch. Moreover, investigating the reaction factors which are expected to affect the water adsorption capacity were studied systematically, including the mass ratio of α-amylase to glucoamylase (m α-amylase/m glucoamylase), the mass ratio of the total amount of enzymes to starch (m enzyme/m St), enzymatic reaction temperature, and enzymatic reaction time. The results suggested that A-type starch has higher enzymolysis efficiency than other types of starch and can be used to produce ideal cavity and pore-size starch granules with potential applications in many fields.

Modern insecticide substitutes using acetylcholine receptors (nAChR) as biochemical targets, such as neonicotinoid insecticides (NNIs), have been extensively researched. Only 12 compounds have been experimentally realized since the initial discovery of imidacloprid. Increasingly, the bottleneck in this field is to rapidly determine the synthesizability of NNI substitutes. Here, we designed a coupled evaluation system for synthesis prediction and validation, including the synthesis probability, reaction path difficulty, and electron transfer characteristics of NNIs and their substitutes. Firstly, a total of 1475 eigenvalues were generated and 52 critical eigenvalues were screened out through the Pearson’s correlation coefficient. The positive and unlabeled (PU) machine learning was constructed using the critical eigenvalues NNIs, including 12 experimentally synthesized NNIs (positive samples) and 73 unsynthesized NNI substitutes (unlabeled samples). Results identified 3 NNI substitutes that were highly promising candidates for synthesis (synthesis probability > 0.5). The results of density functional theory demonstrated the ranking of their reaction ease was UN-1 (31.4 kcal/mol) > UN-2 (81.6 kcal/mol) > UN-3 (3.35 ×103 kcal/mol). Time-dependent density functional theory revealed that changes in the electron distribution and electron excitation type were critical factors affecting their synthesizability, and the local excitation type was more favorable for the synthesizability of NNI substituents. The findings provide significant guidance for NNIs synthesis, reducing the possible space of unlabeled samples to 95.89% of their original size, while also minimizing the cost of research on subsequent NNI substitutes.

Here, we investigated the effects of frying process on the formation of advanced glycation end products (AGEs) in shrimps using Penaeus vannamei as the raw material. The results showed that the oil, malondialdehyde, fluorescent AGEs, carboxymethyl lysine (CML), methylglyoxal hydroimidazolone (MG-H1) and the outer layer carboxyethyl lysine (CEL) content was higher in the fried shrimps than that in the raw unfried shrimps. The outer layer CML, CEL and inner CEL, MG-H1 values all reached the maximum after the first batch of frying (22.43 mg/kg, 304.24 mg/kg, 83.76 mg/kg, and 169.42 mg/kg respectively). However, fluorescent AGEs and MG-H1 of the outer layer reached the maximum after the fifth and fourth batches of frying (1230.0 AU/g and 341.63 mg/kg). Malondialdehyde, fluorescent AGEs, CML, MG-H1, and CEL concentration in the fried shrimps firstly increased and then decreased to stabilization with more frying batches, with higher content in the outer layer of fried shrimps.

Background: While immunosuppressive regimens have improved outcomes in solid organ transplantation, non-immune factors have also been identified as contributors to graft prognosis. Age, gender, hormones, heredity, and other diseases have been recognized to affect organ transplantation. However, the causal relationship between blood lipids and graft dysfunction remains unverified in human clinical investigations. In this study, we employed two-sample Mendelian randomization (MR) to examine the causality between different types of blood lipids and graft dysfunction following organ and tissue transplantation. Methods: We conducted a two-sample MR study using available genome-wide association summary data from the online database MRBASE (http://app.mrbase.org/), which encompasses over 11 billion associations between genetic factors and health-related outcomes, enabling researchers to explore various potential determinants of poor health. The exposure factors included four types of blood lipids: high-density lipoprotein, low-density lipoprotein, cholesterol, and triglycerides. For each exposure factor, three databases were selected for analysis. The outcome factor was the failure and rejection of transplanted organs and tissues. All databases consisted of European population samples, without specific subgroups. The related studies were conducted between 2016 and 2022, and the ''TwoSampleMR'' R package was employed for variant selection. Results: A total of 13 sample groups were collected and analyzed. The results revealed a causal association between blood lipids and graft dysfunction following organ and tissue transplantation. Specifically, the two-sample MR analysis confirmed that low-density lipoprotein and cholesterol levels were significant risk factors for increased graft dysfunction risk after transplantation. Moreover, high-density lipoprotein potentially reduced the risk of allograft dysfunction, while triglycerides possibly elevated the risk. Conclusions: Our recent study provides the initial confirmation that blood lipids may initiate causal pathological processes leading to graft dysfunction after organ and tissue transplantation.

Summary: Background: Inhibiting vascular endothelial growth factor (VEGF) function can improve the efficacy of immunotherapy by modulating the tumor immune microenvironment. AK112 is the first-in-class humanized IgG1 bispecific antibody targeting programmed death-1 (PD-1) and VEGF. This study aimed to evaluate the efficacy and safety of AK112 combined with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Methods: This open-label, multicenter, phase II clinical trial was conducted in 11 hospitals in China. Eligible participants were adults aged 18–75 years with locally advanced or metastatic NSCLC, an Eastern Cooperative Oncology Group performance status of 0 or 1, at least one measurable lesion, and an estimated life expectancy of at least 3 months. The participants were categorized into three cohorts based on prior therapy and functional genomic alterations. Patients in cohort 1 were previously untreated advanced NSCLC, had no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) gene modifications, and received AK112 combined with pemetrexed (500 mg/m2) for non-squamous (non-sq)-NSCLC or paclitaxel (175 mg/m2) for sq-NSCLC plus carboplatin (area under the curve of 5 mg/mL per min) for four cycles, followed by AK112 with pemetrexed for non-sq-NSCLC and AK112 alone for sq-NSCLC as maintenance therapy. The participants in cohort 2 had advanced NSCLC with EGFR-sensitive mutations, failed previous EGFR-tyrosine kinase inhibitor (TKI) therapy, and received pemetrexed plus AK112 and carboplatin for four cycles, followed by pemetrexed plus AK112 as maintenance therapy. The participants in cohort 3 had advanced NSCLC who failed systemic platinum-based chemotherapy and anti-PD-1/programmed death-ligand 1 (PD-L1) treatments and received AK112 plus docetaxel (75 mg/m2). Two dosages of AK112 (10 or 20 mg/kg) were examined in each cohort, and the drug was administered intravenously on day 1 of each 3-week treatment cycle. The primary endpoints were the investigator-assessed objective response rate (ORR) and safety. This study was registered with ClinicalTrials.gov (NCT04736823). Findings: Eighty-three patients were enrolled from February 2021 to August 2022 and received the study treatment. Cohorts 1, 2, and 3 had 44, 19, and 20 patients, respectively. The confirmed ORR was 53.5% (23/43) [95% CI, 36.9–67.1], 68.4% (13/19) [95% CI, 43.4–87.4], and 40.0% (8/20) [95% CI, 19.1–63.9] in cohorts 1, 2, and 3, respectively. In cohort 1, the median PFS was not reached, and the 12-month PFS rate was 59.1%. In cohorts 2 and 3, the median PFS were 8.5 [95% CI, 5.5-NE] and 7.5 [95% CI, 2.3-NE] months, and the 12-month PFS rates were 35.5% and 44.5%, respectively. The most common grade ≥3 treatment-related adverse events were decreased white blood cell count [7 (8.4%)], neutropenia [5 (6.0%)], thrombocytopenia [2 (2.4%)], anemia [4 (4.8%)], and myelosuppression [2 (2.4%)]. Interpretation: AK112 plus platinum-doublet showed promising antitumor activity and safety not only in first-line treatment of advanced NSCLC patients without driver mutation but also in patients with EGFR-functional mutation who failed previous EGFR-TKI therapy and advanced NSCLC patients who failed prior systemic platinum-based chemotherapy and PD-1/PD-L1 inhibitor treatments, suggesting a valuable potential new treatment option for this patient population. Funding: Akeso Biopharma, Inc., Zhongshan, China, and National Natural Science Foundation of China.

Summary: The immune and stromal contexture within the tumor microenvironment (TME) interact with cancer cells and jointly determine disease process and therapeutic response. We aimed at developing a risk scoring model based on TME-related genes of squamous cell lung cancer to predict patient prognosis and immunotherapeutic response. TME-related genes were identified through exploring genes that correlated with immune scores and stromal scores. LASSO-Cox regression model was used to establish the TME-related risk scoring (TMErisk) model. A TMErisk model containing six genes was established. High TMErisk correlated with unfavorable OS in LUSC patients and this association was validated in multiple NSCLC datasets. Genes involved in pathways associated with immunosuppressive microenvironment were enriched in the high TMErisk group. Tumors with high TMErisk showed elevated infiltration of immunosuppressive cells. High TMErisk predicted worse immunotherapeutic response and prognosis across multiple carcinomas. TMErisk model could serve as a robust biomarker for predicting OS and immunotherapeutic response.

Exposure to the toxic metal cadmium (Cd) is a well-established risk factor for hepatic inflammation, but it remains unclear how metabolic components, such as different fatty acids (FAs), interact with Cd to influence this process. Understanding these interactions is essential for identifying potential preventative and therapeutic targets for this disorder. To address this question, we conducted in vitro and in vivo studies to investigate the combinatorial effect of Cd and saturated FAs on hepatic inflammation. Specifically, we assessed the cytotoxicity of Cd on macrophages and their polarization and inflammatory activation upon co-exposure to Cd and saturated FAs. Our results showed that while saturated FAs had minimal impact on the cytotoxicity of Cd on macrophages, they significantly collaborated with Cd in predisposing macrophages towards a pro-inflammatory M1 polarization, thereby promoting inflammatory activation. This joint effect of Cd and saturated FAs resulted in persistent inflammation and hepatic steatohepatitis in vivo. In summary, our study identified macrophage polarization as a novel mechanism by which co-exposure to Cd and saturated lipids induces hepatic inflammation. Our findings suggest that intervening in macrophage polarization may be a potential approach for mitigating the adverse hepatic effects of Cd.

Gonorrhea is the second most common sexually transmitted diseases worldwide. Chronic infection of Neisseria gonorrhoeae (N. gonorrhoeae) can lead to severe complications. Presently, N. gonorrhoeae has developed resistance to almost all antibiotics used for the treatment of gonorrhea. Thus, it's urgent to explore new approaches to treat gonorrhea. Presently, nontraditional treatment method as an alternative to antibiotic use is getting more and more attention. Here we demonstrated that 18β-glycyrrhetinic acid (GRA) exhibited robust antimicrobial activity against N. gonorrhoeae in vitro. GRA led to a significant decline in viable N. gonorrhoeae in a dose dependent manner compared with DMSO treatment (P

The accumulation of potentially harmful substances in tea garden soils and tea leaves, especially persistent organic pollutants (POPs), is a special concern for tea consumers worldwide. However, their potential health and ecological risks in tea gardens have rarely been investigated. This study proposed measures to improve the degradation ability of POPs by the tea rhizosphere and to reduce the human health risks caused by POPs after tea consumption. In this study, the binding energy values of six types of POPs and the degraded protein were used to reflect the degradation ability and calculated using molecular dynamic simulations. The main root secretions (i.e., catechin, glucose, arginine, and oxalic acid) were selected and applied with a combination of tea fertilizer and trace element combination (i.e., urea, straw, and copper element), leading to an improved degradation ability (49.59 %) of POPs. To investigate the mechanisms of the factors that affect the degradation ability, molecular docking, tensor singular value decomposition methods, multivariate correlation analysis and 2D-QSAR model were used. The results showed that the solvation energy and solvent accessible surface area are the main forces, and the molecular weight, boiling point, and topological radius of the POPs were the key molecular features affecting their degradation ability. Based on the three key characteristics, a diet avoidance scheme (i.e., avoiding lysine, maslinic acid, ethanol, perfluorocaproic acid, and cholesterol with tea), which can reduce the binding ability of POP residues to aromatic hydrocarbon receptors by 506.13 %. This work will provide theoretical strategies to improve the quality and safety of tea production and reduce the potential risks of harmful substance residues in tea garden soils and tea leaves.

Lead alloy is used as coolant in Lead-based cooled Fast Reactor (LFR). The natural characteristics of lead alloy are combined with the simple structural design of LFR. This constitutes the inherent safety characteristics of LFR. The main work of this paper is to take the main coolant pump (MCP) in the lead-cooled fast reactor (LFR) as the research object, and to study the flow pattern distribution of the internal flow field under the reverse rotation pump condition, the reverse rotation positive-flow braking condition and the reverse rotation negative-flow braking condition. In this paper, the double-outlet volute type and the space guide vane are selected as the potential designs of the CLEAR-I MCP. In this paper, the CFD method is used to study the potential reverse accident of the MCP. It is found that the highest flow velocity in the impeller appears at the impeller outlet, and the Q-H curves of the two design programs basically coincide. The space guide vane type MCP has better hydraulic performance under the reverse rotation positive-flow condition, the Q-H curves of the two designs gradually separate with increasing flow rate, and the maximum flow velocity inside the space guide vane type MCP is obviously lower than that of the double-outlet volute type. For the reverse rotation test of MCP, only the condition of the forward rotating pump of the main coolant pump is tested and verified. For the simulation of the MCP in LBE medium, it proved that the turbulence model and basic settings selected in the simulation are reliable.

Summary: The role of tripartite motif (TRIM) 38, a ubiquitin E3 ligase regulating various pathophysiological processes, in cardiac fibrosis remains unclear. Here, a model of angiotensin II and myocardial infarction (MI)-induced fibrosis was established to explore its role in cardiac fibrosis and its underlying mechanisms. Cardiac fibrosis in the mouse MI model was mitigated by TRIM38 overexpression, but aggravated by its depletion. Consistently, in vitro overexpression or knockdown of TRIM38 ameliorated or aggravated the proliferation and secretion of cardiac fibroblasts (CFs) exposed to fibrotic stimulation, respectively. Mechanistically, TRIM38 suppressed cardiac fibrosis progression by attenuating TAK1/MAPK signaling. Inhibiting TAK1/MAPK signaling with a pharmacological inhibitor greatly reversed the effects of TRIM38 knockdown on CF secretion. Specifically, TRIM38 interacted with and “targeted” TAB2 and TAB3 for degradation, subsequently inhibiting TAK1 phosphorylation and negatively regulating MAPK signaling. These findings can help develop therapeutic strategies to treat and prevent cardiac fibrosis.

With the extensive use of antibiotics, the problem of antibiotic resistance genes (ARGs) has gradually emerged. As agricultural soil is an important enrichment media of antibiotics and ARGs, it is particularly important to study the toxicity of ARGs, the effects of various nutrients and pollutants, and how to control them through source modification and process regulation. In this study, a combination of source modification and process regulation was used to weaken the toxic expression of Quinolones’ (QNs’) ARGs in soils from different agricultural areas. And the influence of soil nutrients and pollutants on this process will be explored. Protein-protein docking and molecular docking were used to construct a target protein complex for the toxic expression of QNs’ ARGs and characterize the toxicity of QNs’ ARGs. The two-dimensional and three-dimensional quantitative structure-activity relationships model construction and sensitivity analysis were used to molecular modification and related validation. Molecular dynamics simulations assisted by sampling survey method based on agricultural soils in Northeast China and the lower-middle reaches of the Yangtze River were carried out to generate four scenarios. The main results are: (a) A functionally improved and environmentally friendly quinolone derivative (ORB–19) was designed. It can effectively inhibit the expression of QNs’ ARGs and weaken the antibiotic selection pressure risk. The application of ORB–19 in agricultural areas could significantly inhibit the toxic expression of QNs’ ARGs (112.75%~169.59%); (b) QNs’ ARGs have a stronger toxic expression in agricultural areas of Northeast China, which have higher nutrient elements; (c) The contribution of different types of agricultural pollution to suppressing the toxic expression of QNs' ARGs in agricultural soils varies; (d) The options of applied field measures given for the inhibition of QNs’ ARG toxic expression varied between plots with different agricultural pollution types. This study provides theoretical support for inhibiting the toxic expression of QNs’ ARGs in the soil environment, reducing the spread of ARGs in microbial populations, replacing green QNs derivatives, and sustainable development of agricultural soils.

Natural odour compounds could be a potential alternative to synthetic herbicides. The odour compound of Periploca sepium Bunge, named 2-hydroxy-4-methoxy-benzaldehyde (HMB), is a herbicidal compound. However, its herbicidal mechanism is unclear. In this experiment, the physiological and biochemical indices, ultrastructure, and photosynthetic function of the leaves of Humulus scandens (Lour.) Merr. treated by HMB were assessed to elucidate the herbicidal mechanism. The results of physiological and biochemical indices are as follows: First, after 4 h of treatment with 2.5 and 5.0 mg/mL, the damage rates in the membrane permeation assay were 74.7% and 89.1%, respectively. Second, compared to the negative control group, multiple physiological and biochemical indices of the two treated groups were changed, including catalase content (−18.5 and −26.5 ng/mL), superoxide dismutase content (−27.4 and −56.6 ng/mL), peroxidase content (382.0 and 880.0 ng/mL), reactive oxygen species content (16.7 and 27.2 ng/mL), malondialdehyde content (8.9 and 25.2 nmol/g), and water potential values (0.2 and 0.3 MPa), except for the photosynthetic pigment contents (chlorophyll a, b, and carotene). Furthermore, the results of transmission electron microscopy showed that the organelles in the mesophyll tissue cells disappeared and severe plasmolysis led to cell atrophy after 4 h of treatment. There were fewer starch granules after 24 h of treatment, but there was no obvious abnormality in the upper and lower epidermal cells. The results of photosynthetic function showed that in the light response, the net photosynthetic rate (Pn), transpiration rate (Tr), stomatal conductance (Gs), and stomatal limitation value of the tested leaves were lower than those of the negative control group by 26.6 μmol·m−2·s−1, 7.7 mmol·m−2·s−1, 0.9 mol·m−2·s−1, and 0.2, respectively. However, the intercellular CO2 concentration (Ci) increased and was higher than the air CO2 concentration. In the CO2 response, the Pn, Tr and Gs of the tested leaves first increased and then decreased, but the Ci value continuously increased and finally reached 1727.5 μmol·mol−1. It is obvious that HMB may have inhibited the effect on the photosynthetic system of the tested leaves. Overall, HMB killed the weeds by destroying the structure and multiple physiological functions of the tested leaves.

Synthetic musks (SMs) have been widely used as odor additives in personal care products (PCPs). Dermal exposure to SMs is the main pathway of the accumulation of these chemicals in human kerateins and poses potential health risks. In this study, in silico methods were established to reduce the human health risk of SMs from dermal exposure by investigating the risk mechanisms, designing lower bioaccumulation ability SMs and suggesting proper PCP ingredients using molecular docking, molecular dynamics simulation, and quantitative structure-activity relationship (QSAR) models. The binding energy, a parameter reflecting the binding ability of SMs and human keratin protein (4ZRY), was used as the indicator to assess the human health risk of SMs. According to the mechanism analysis, total energy was found as the most influential molecular structural feature influencing the bioaccumulation ability of a SM, and as one of the main factors influencing the function (i.e., odor sensitivity) of an SM. The 3D-QSAR models were constructed to control the human health risk of SMs by designing lower-risk SMs derivatives. The phantolide (PHAN)− 58 was determined to be the optimum SM derivative with lower bioaccumulation ability (reduced 17.25%) and improved odor sensitivity (increased 7.91%). A further reduction of bioaccumulation ability of PHAN-58 was found when adding proper body wash ingredients (i.e., alkyl ethoxylate sulfate (AES), dimethyloldimethyl (DMDM), EDTA-Na4, ethylene glycol distearate (EGDS), hydroxyethyl cellulose (HEC), lemon yellow and octyl glucose), leading to a significant reduction of the bioaccumulation ability (42.27%) compared with that of PHAN. Results demonstrated that the proposed theoretical mechanism and control strategies could effectively reduce the human health risk of SMs from dermal exposure.

Exposure to cadmium (Cd), a toxic metal, is epidemiologically linked to nonalcoholic steatohepatitis (NASH) in humans. However, the role of Cd in NASH remains to be fully elucidated. This study employed a novel murine NASH model to investigate the effects of chronic low-dose Cd on hepatic pathology and its underlying mechanisms. NASH is characterized by lipid accumulation, extensive cell death, and persistent inflammation in the liver. We found that treatment with Cd in drinking water (10 mg/L) for 6 or 12 weeks significantly boosted hepatic fat deposition, increased hepatocyte destruction, and amplified inflammatory responses in mice, confirming that low-dose Cd can facilitate NASH development in vivo. Mechanistically, chronic Cd exposure reshaped the hepatic transcriptional landscape, with PPAR-mediated fatty acid metabolic pathways being the most significantly altered. In particular, Cd repressed fatty acid desaturation, leading to the accumulation of saturated fatty acids whose lipotoxicity exacerbated cell death and, consequently, inflammatory activation. In summary, we validated the causal effects of chronic low-dose Cd on NASH in vivo and identified the fatty acid desaturation program as a novel target for Cd to instigate hepatopathological alterations.

Various Ni and Ni-Sn catalysts supported on TiO2 were prepared and the catalytic activities were evaluated for ethanol formation from aqueous acetic acid. Although catalytic activities of the Ni/TiO2 catalysts were limited, the addition of Sn improved the activity dramatically, and the optimum Ni/Sn ratio was approximately 1:1 (w/w). SnO2, the precursor of Sn, could not be reduced into metal Sn in pure form but did reduce into Ni-Sn alloys in the presence of NiO, the precursor of Ni. Analyses with XRD and SEM-EDS revealed that the Ni-Sn alloys were homogeneously dispersed on the TiO2 surface. Furthermore, IR analysis indicated that the Ti atoms in the catalyst act as a Lewis acid, which coordinates to the oxygen atoms of acetic acid, enhancing the attack of hydrogens activated on neighboring Ni-Sn alloys. Based on these results, Ni-Sn/TiO2 is proposed as an effective hydrogenation catalyst for converting aqueous acetic acid into ethanol.

Synthetic musks (SMs) are odor additives commonly used in the personal care products. Their wide existence in the environment and the recently reported adverse impact on the production and activity of progesterone and estrogen have raised pregnancy red flags and even lead to a pregnancy loss. Apart from the suggestion of limiting SM contact and exposure, effective abortion risk control measures for SMs remain to be blank. Facing the above challenges, this study tried to establish a new theoretical circumvention strategy to reduce the abortion risk of SMs to pregnant women by designing the supplementary diet plan and environmentally friendly SMs derivatives using molecular docking and three-dimensional quantitative structure–activity relationship (3D-QSAR) models. According to the supplementary diet plan, the diet combination of vitamin E, vitamin B2, niacin, vitamin A, and vitamin B6 were confirmed to not only provide essential nutrients for human health, but also reduce the abortion risk in pregnant women in daily life. The multi-activity (binding ability of SMs with progesterone-estrogen) 3D-QSAR model was constructed to screen SMs derivatives. The LibDock score, a parameter reflecting the binding ability between SMs’ Derivative-24 with progesterone-estrogen, decreased as much as 137.67% compared with its precursor galaxolide (HHCB). The 3D-QSAR models assisted screening indicated that Derivative-24 had lower environmental impacts (i.e., bioconcentration and mobility) and improved functional properties (odor stability, musky scent, and odor intensity). The integration of the optimum candidate, Derivative-24, with optimum three supplementary diet plans exhibited a much lower abortion risk than HHCB, demonstrating the effectiveness of the proposed theoretical circumvention strategy as a comprehensive abortion risk control measure. It also shed light on the design of new pharmaceutical and personal care products using advanced computing tools.

In this work a carbon nanotube–Ce-modified PbO2 (CNT–Ce–PbO2) electrode was prepared by electrodeposition method, and compared with pure PbO2, Ce–PbO2, and CNT–PbO2 electrodes. The direct and indirect oxidation capacities of prepared electrodes in electro-catalytic oxidation processes were investigated by cyclic voltammetry and hydroxyl radical production tests, respectively. The electro-catalytic activity of electrodes was examined by electro-catalytic oxidation of a model pollutant of m-nitrophenol (m-NP). Besides, high-performance liquid chromatography (HPLC) was also employed to identify the products resulting from the electro-catalytic oxidation of m-NP and the degradation mechanism of m-NP was proposed. Results show that the CNT–Ce–PbO2 anode has higher direct and indirect oxidation capacities than pure PbO2, Ce–PbO2, and CNT–PbO2 anodes. In the electro-catalytic oxidation of m-NP, the m-NP can be oxidized and degraded at all anodes, and the oxidation reactions of m-NP follow first-order kinetics. m-NP and TOC removal efficiencies are about 0.987 and 0.622 after electrolysis of 120 min and a maximum first-order rate constant of 0.036 min−1 is achieved at the CNT–Ce–PbO2 anode, which are obviously higher than those of the other three kinds of anodes. Keywords: Electro-catalytic oxidation, PbO2 electrode, Carbon nanotube, Ce, m-Nitrophenol

Oxidative stress and excessive lipid accumulation in liver tissues are considered as important factors in development of non-alcoholic fatty liver disease (NAFLD), which is the most common chronic liver disease worldwide and strongly associated with insulin resistance, obesity and dyslipidemia. In this study, the effect of PMFs-enriched extract of Daoxianyeju (Citrus daoxianensis S.W. He) (EDX) on NAFLD were examined using high fat diet-induced obesity (DIO) C57BL/6 mice. Daily supplementation of 0.2% and 0.5% EDX with high fat diet (w/w) over ten weeks markedly improved glucose tolerance and insulin resistance as well as lipid profiles, alleviated hepatic steatosis, inflammatory and oxidative stress. The benefit of EDX on improving pathology of NAFLD induced by high fat diet may associate with the activation of nuclear factor erythroid-2 related factor 2 (Nrf2) pathways in liver tissues. Our study showed that citrus PMFs may use as a dietary therapy for NAFLD and related metabolic disorders.

The rapid increase of neonicotinoid insecticides (NNIs) leads to the resistance to target organisms and risks to non-target organisms in the ecosystem. Thus, we designed a multi-criteria framework for resistance to target organisms, exposure risks to non-target organisms under spraying and soil or seed treatment scenarios, and ruled out the NNIs on the priority control lists. The resistance and cross-resistance, as well as the toxicity (i.e., acute, chronic, and combined toxicities) were characterized and evaluated. Results showed that the cross-resistance between two NNIs (i.e., CLO and FLU) was 1.8 times higher than their single resistance. A medium to extra-high toxicity level of NNIs was found in non-target organisms. Regulation strategies for NNIs resistance and toxicity were also proposed. The best synergist blocking and control scheme for resistance and toxicity was screened out when three main synergists (i.e., TPP: DEM: PBO) with the ratio of 1:1:1. Four NNIs (i.e., NPM, IMI, ACE, TMX) used in grain crops and six NNIs (i.e., NPM, IMI, ACE, TMX, CLO, THI) used in vegetable crops were determined as the ruled-out pesticides on the priority control lists. This study highlights the adverse effects of NNIs on the ecosystem and human health which should not be overlooked., (Copyright © 2022 Elsevier B.V. All rights reserved.)