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Introduction: The looming antibiotic-resistance problem has imposed an enormous crisis on global public health and agricultural development. Even worse, the evolution and widespread distribution of antibiotic-resistance elements in bacterial pathogens have made the resurgence of diseases that were once easily treatable deadly again. The development of antibiotics with novel mechanisms of action is urgently required., Objectives: Inspired by charming activity-based protein profiling (ABPP) technology and increasing attention to quinazolines in the development of antibacterial agents, this study engineered a series of new quinazoline derivatives, assessed their antibacterial profiles, and first identified the possible target., Methods: The target identification and their possible binding sites were verified by ABPP technology, molecular docking, and molecular dynamic simulations. The fatty acid synthesis process was analyzed by gas chromatography, propidium iodide staining, and scanning electron microscopy. The physicochemical properties and fungicide-likeness were evaluated using the Fungicide Physicochemical-properties Analysis Database., Results: Compound 7a, an acrylamide-functionalized quinazoline derivative, exhibited excellent antibacterial potency against Xanthomonas oryzae pv. oryzae with an EC 50 value of 13.20 µM. More importantly, ABPP technology showed that β-ketoacyl-ACP-synthase Ⅱ (FabF) was the first identified quinazolines' potential target. Compound 7a could selectively bind to the Cys151 residue of FabF through covalent interaction, suppress fatty acid biosynthesis, and damage the cell membrane integrity, thereby killing the bacteria. The pot experiment results showed that compound 7a demonstrated protective and curative values of 49.55 % and 47.46 %, surpassing controls bismerthiazol and thiodiazole copper. Finally, compound 7a exhibited low toxicity towards non-target organisms. These unprecedented performances contributed to excavating new quinazoline-based bactericidal agents., Conclusion: Our research highlights the superiority of ABPP technology, for the first time, identifies the target of engineered quinazolines in pathogenic bacteria, and their potential target fished by ABPP tools holds great promise for the development of quinazoline-based and/or FabF-targeted bactericides., 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. Production and hosting by Elsevier B.V.)

Endothelial cell (EC) dysfunction within the aorta has long been recognized as a prominent contributor to the progression of atherosclerosis and the subsequent failure of vascular graft transplantation. However, the direct relationship between EC dysfunction and vascular remodeling remains to be investigated. In this study, we sought to address this knowledge gap by employing a strategy involving the release of glutamine synthetase (GS), which effectively activated endothelial metabolism and mitigates EC dysfunction. To achieve this, we developed GS-loaded small-diameter vascular grafts (GSVG) through the electrospinning technique, utilizing dual-component solutions consisting of photo-crosslinkable hyaluronic acid and polycaprolactone. Through an in vitro model of oxidized low-density lipoprotein-induced injury in human umbilical vein endothelial cells (HUVECs), we provided compelling evidence that the GSVG promoted the restoration of motility, angiogenic sprouting, and proliferation in dysfunctional HUVECs by enhancing cellular metabolism. Furthermore, the sequencing results indicated that these effects were mediated by miR-122-5p-related signaling pathways. Remarkably, the GSVG also exhibited regulatory capabilities in shifting vascular smooth muscle cells towards a contractile phenotype, mitigating inflammatory responses and thereby preventing vascular calcification. Finally, our data demonstrated that GS incorporation significantly enhanced re-endothelialization of vascular grafts in a ferric chloride-injured rat model. Collectively, our results offer insights into the promotion of re-endothelialization in vascular grafts by restoring dysfunctional ECs through the augmentation of cellular metabolism., 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 Ltd. All rights reserved.)

Neutron activation analysis is a highly sensitive non-destructive testing technique with important applications in industry, geoscience, medical therapy, etc. This work designed and optimized a thermal neutron device that utilized a portable D-D neutron generator, and the Monte Carlo method with the Geant4 toolkit was applied to simulation. The objective of the optimized design is to maximize the thermal neutron flux at the output surface and increase the utilization efficiency of the neutron generator. A parameter K was defined as a measure of the device's slowing capacity for neutrons and was used to determine the optimized device geometry. The simulation considered the contribution of different types and sizes of moderators and reflectors to the thermal neutron intensity to obtain the optimal size. The shielding protection of the device was then designed. The effectiveness of shielding with different thicknesses was evaluated using three dose reference points. The results indicated that the optimized device can achieve a maximum thermal neutron flux of 1.97 × 10 5 n∙cm -2 ∙s -1 at the output surface by using high-density polyethylene (HDPE) as the moderator and nickel as the reflector. It was determined that using 45 cm of HDPE and 9 cm of lead protection in sequence along the neutron head axis would reduce the dose rate at the reference point, located 5 cm from the surface of the device, below the safety limit of 2.5 μSv/h., 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 Ltd. All rights reserved.)

A polyelectrolyte system consisting of sodium alginate (SA) and quaternary ammonium chitosan (QAC) blended with polydopamine-coated copper sulfide particles (CuS@PDA) was chosen to investigate the function of CuS@PDA in the uniform binary blending of anionic and cationic polyelectrolytes in detail. A smart composite fiber SA/QAC/CuS@PDA was prepared via a dry-wet spinning technique. With the addition of CuS@PDA (about 4.3 % in fiber), the as-prepared SA/QAC/CuS@PDA-0.50 fibers (SQCuS@P-0.50 SCFs) showed notably enhanced intensity 359.2 MPa, excellent moisture response, and photothermal conversion performance, with the temperature increasing from 25.9 to 80.7 °C as irradiated under a 980 nm infrared lamp at distance 20 cm away for 120 s. The photothermal performance was maintained after 6 lighting on-and-off cycles. The tensile strength decreased ~23.8 % after 4 cycles, then remained fixed. The diameter increases to ~480 % in wet state but decreases to the original size in dry state for 10 cycles. When the fabric with 90 wt% SQCuS@P-0.50 SCFs was used as a water evaporator, the water evaporation rate and efficiency were 1.68 kg·m -2 ·h -1 and 102 % under 1 sun irradiation. This work provides a simple and ecofriendly strategy for fabricating photothermal fabrics by designing and preparing composite fibers., 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.)

In this study, a tick intracellular symbiont, Candidatus Midichloria mitochondrii, was detected in Hyalomma anatolicum from Xinjiang, China. Morphological identification and cytochrome oxidase subunit I sequence alignment were used for molecular identification of the tick species. PCR detection further revealed the presence of endosymbiont C. M. mitochondrii in the tick. Specific primers were designed for Groel and 16S rRNA genes of C. M. mitochondrii for PCR amplification and phylogenetic analysis. To further investigate the vertical transmission characteristics of C. M. mitochondrii, specific primers were designed based on the FabⅠ gene fragment to detect C. M. mitochondrii in different developmental stages and organs of the tick using qPCR. Of the 336 tick specimens collected from the field, 266 samples were identified as H. anatolicum on the basis of morphological characteristics. The gene fragment alignment results of COI confirmed that these ticks were H. anatolicum. The phylogenetic analysis showed that Groel gene of C. M. mitochondrii clustered with Midichloria strains detected in Ixodes ricinus ticks from Italy and Ixodes holocyclus ticks from Australia, with 100% sequence similarity. Furthermore, the 16S rRNA gene of C. M. mitochondrii clusters with the strains isolated from Hyalomma rufipes ticks in Italy, exhibiting the highest degree of homology. qPCR results showed that C. M. mitochondrii was present at all developmental stages of H. anatolicum, with the highest relative abundance in eggs, and lower relative abundance in nymphs and unfed males. With female tick blood feeding, the relative abundance of C. M. mitochondrii increased, and a particularly high relative abundance was detected in the ovaries of engorged female ticks. This study provides information for studying the survival adaptability of H. anatolicum, and provides data for further investigation of the mechanisms regulating tick endosymbionts in ticks, enriching the reference materials for comprehensive prevention and control of tick-borne diseases., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nothing 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 © 2024 Elsevier Inc. All rights reserved.)

Background: GPNMB is a type I transmembrane protein, and emerging evidence supports the relationship between GPNMB and cancers., Objective: Through a comprehensive pan-cancer analysis, we examined the expression levels, prognostic significance, and mutation profiles of GPNMB in different cancer types. Subsequently, utilizing in vitro experiments, we elucidated the impact of GPNMB in endometrial cancer (EC)., Methods: TIMER2, GEPIA2, UALCAN and cBioPortal were used to analyze the expression pattern, prognostic values, and mutation status of GPNMB. HEC-1B and Ishikawa cells were used to conduct in vitro analyses of GPNMB overexpression. GeneMANIA and TIMER2 were used to evaluate the potential functions and correlations between GPNMB expression and tumor-infiltrating immune cells in EC., Results: GPNMB was found to be highly expressed in multiple cancers, where it was associated with poor prognosis. Additionally, GPNMB was downregulated at both mRNA and protein levels in EC. Overexpression of GPNMB inhibited the proliferation, migration, and invasion of HEC-1B and Ishikawa cells. Functional analysis showed that GPNMB was enriched in pathways associated with regulation of plasma lipoprotein particle levels. The expression of GPNMB was positively connected with B cell, CD8+ T cell, CD4+ T cell, Macrophage, Neutrophil, and Dendritic cell levels., Conclusion: Through pan-cancer analysis, we identified the antitumor effect of GPNMB in EC and predicted the potential mechanisms between GPNMB expression and EC., (© 2024. The Author(s).)

An enzyme catalyzed strategy for the synthesis of a chiral hydrazine from 3-cyclopentyl-3-oxopropanenitrile 5 and hydrazine hydrate 2 is presented. An imine reductase (IRED) from Streptosporangium roseum was identified to catalyze the reaction between 3-cyclopentyl-3-oxopropanenitrile 5 and hydrazine hydrate 2 to produce trace amounts of ( R )-3-cyclopentyl-3-hydrazineylpropanenitrile 4 . We employed a 2-fold approach to optimize the catalytic performance of this enzyme. First, a transition state analogue (TSA) model was constructed to illuminate the enzyme-substrate interactions. Subsequently, the Enzyme_design and Funclib methods were utilized to predict mutants for experimental evaluation. Through three rounds of site-directed mutagenesis, site saturation mutagenesis, and combinatorial mutagenesis, we obtained mutant M6 with a yield of 98% and an enantiomeric excess (ee) of 99%. This study presents an effective method for constructing a hydrazine derivative via IRED-catalyzed reductive amination of ketone and hydrazine. Furthermore, it provides a general approach for constructing suitable enzymes, starting from nonreactive enzymes and gradually enhancing their catalytic activity through active site modifications.

6PPD and its oxidation product, 6PPD-quinone have garnered widespread attention due to their adverse effects on aquatic ecosystems and human health, and are recognized as emerging pollutants. In this study, we investigated the interaction mechanism between 6PPD/6PPD-quinone and human serum albumin (HSA) through various experiments. Experimental findings reveal that the IC 50 values of 6PPD-quinone and 6PPD against HEK293T cells were 11.78 and 40.04 μM, respectively. Additionally, the cytotoxicity of these compounds was regulated by HSA, displaying an inverse correlation with their binding affinity to HSA. Furthermore, 6PPD/6PPD-quinone can spontaneously insert into site I on HSA, forming a binary complex that induces changes in the secondary structure of HSA. However, their effects on the esterase-like activity of HSA exhibit a dichotomy. While 6PPD activates the esterase-like activity of HSA, 6PPD-quinone inhibits it. Molecular docking analyses reveal that both 6PPD and 6PPD-quinone interact with many amino acid residues on HSA, including TRP214, ARG222, ARG218, ALA291, PHE211. The π electrons on the benzene rings of 6PPD/6PPD-quinone play pivotal roles in maintaining the stability of complexes. Moreover, the stronger binding affinity observed between 6PPD and HSA compared to 6PPD-quinone, may be attributed to the larger negative surface potential of 6PPD., 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 Ltd. All rights reserved.)

Objective: To investigate whether transcutaneous electrical acupoint stimulation (TEAS) at PC6 could reduce hypotension after spinal anesthesia (SA) in parturients and to compare the effect of TEAS at different frequencies. Methods: From February 20, 2023, to August 29, 2023, 90 parturients scheduled for c-section under SA were randomly assigned to receive no treatment (Control), TEAS at high frequency (TEAS-HF), or TEAS at low frequency (TEAS-LF). Treatments started immediately after SA and lasted for 30 min. The primary endpoint was incidence of hypotension by 30 min after SA. Secondary endpoints included lowest systolic blood pressure (SBP) during 30 min after SA, dose of ephedrine, dose of atropine, Apgar score at 1 min, and adverse events, including nausea, vomiting, dizziness, dyspnea, and chest congestion. Results: In the TEAS-HF group, the incidence of hypotension by 30 min after SA was lower (13.3%) than in the Control (53.3%, p  = 0.001; OR 1.9, 95% confidence interval [CI]: 1.2-2.8) and TEAS-LF group (40.0%, p  = 0.02, OR 1.4, 95% CI: 1.0-2.0). The lowest SBP during 30 min after SA was higher in the TEAS-HF group (100.0 ± 9.4 mm Hg) than in the Control group (91.5 ± 16.5 mm Hg) and TEAS-LF group (93.9 ± 16.6 mm Hg). Patients who received TEAS showed a lower score of nausea and vomiting (both p  = 0.02). Patients in the group TEAS-HF showed a lower incidence of dizziness, dyspnea, and of chest congestion than those in the other two groups. There was no difference with respect to atropine consumption and neonatal Apgar score. Conclusions: TEAS-HF at PC6 reduced hypotension after SA in parturients, while TEAS-LF did not. Trial registration: ClinicalTrials.gov (NCT05724095).

Removing heavy metals from aqueous solutions has drawn more and more attentions these years because of their serious global health challenge to human society. To develop an adsorbent with green, stable and high-efficiency for adsorption of heavy metals, pectin β-cyclodextrin composite was successfully prepared and used for Zn 2+ and Cu 2+ adsorption for the first time. Various variables that influence the adsorption performance were explored, and the optimal adsorption conditions were determined. According to the pseudo-second-order kinetic model, the adsorption process of Zn 2+ and Cu 2+ by the adsorbent was mainly chemical adsorption. The adsorbent adsorption process was an exothermic and non-spontaneous process. According to the Langmuir isotherm model, the maximum adsorption capacity was 12.51 ± 0.33 and 24.98 ± 0.23 mg/g for Zn 2+ and Cu 2+ , respectively. The FTIR, EDX and XPS results revealed that the main mechanisms of removing pollutants by adsorbent were ion exchange and coordination. In addition, electrostatic attraction and chelation were present in the adsorption process. After five adsorption desorption cycles, the pectin β-cyclodextrin composite adsorbent still exhibited adsorption and regeneration capabilities. This study provides a low-cost, effective and simple method for preparation of modified pectin, which has excellent application potential in the removal of heavy metal ions from wastewater., 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.)

Lactate dehydrogenase (LDH), a crucial enzyme in anaerobic glycolysis, plays a pivotal role in the energy metabolism of tumor cells, positioning it as a promising target for tumor treatment. Rutin, a plant-based flavonoid, offers benefits like antioxidant, antiapoptotic, and antineoplastic effects. This study employed diverse experiments to investigate the inhibitory mechanism of rutin on LDH through a binding perspective. The outcomes revealed that rutin underwent spontaneous binding within the coenzyme binding site of LDH, leading to the formation of a stable binary complex driven by hydrophobic forces, with hydrogen bonds also contributing significantly to sustaining the stability of the LDH-rutin complex. The binding constant (K a ) for the LDH-rutin system was 2.692 ± 0.015 × 10 4 M -1 at 298 K. Furthermore, rutin induced the alterations in the secondary structure conformation of LDH, characterized by a decrease in α-helix and an increase in antiparallel and parallel β-sheet, and β-turn. Rutin augmented the stability of coenzyme binding to LDH, which could potentially hinder the conversion process among coenzymes. Specifically, Arg98 in the active site loop of LDH provided essential binding energy contribution in the binding process. These outcomes might explain the dose-dependent inhibition of the catalytic activity of LDH by rutin. Interestingly, both the food additives ascorbic acid and tetrahydrocurcumin could reduce the binding stability of LDH and rutin. Meanwhile, these food additives did not produce positive synergism or antagonism on the rutin binding to LDH. Overall, this research could offer a unique insight into the therapeutic potential and medicinal worth of rutin., 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.)

Tetrahydrocurcumin (THC), as a novel food supplement, has generated significant interests for its potential impact on health and nutrition. Pepsin serves as the primary enzyme involved in the digestive mechanism. This research investigated the conformational and functional alterations of pepsin induced by THC using multispectral techniques and computer simulations. The results showed that THC enters the cavity of pepsin, in which hydrophobic forces play a major role. The binding constant is 1.044 × 10 4  M -1 at 310 K. The upregulation or downregulation effect of THC on pepsin activity depends on its concentration. Molecular docking outcomes indicated that THC was encapsulated by various amino acids and established H-bonds with Tyr189 and Ser294, revealing that hydrogen bonds also contribute to maintaining the stability of THC-pepsin complex. In addition, the altered activity of pepsin may be related to the interaction between THC and the amino acids at the active site (Asp32) according to energy contribution results. 3D fluorescence spectroscopy, CD spectra and molecular dynamic simulations show that THC causes conformational changes in pepsin. The existence of THC makes pepsin structure to be less dense, leading to the decrease of energy traps. This suggests that pepsin becomes conformationally more suitable to bind to THC., 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: There is a scarcity of prospective clinical research evidence regarding the utilization of transvaginal natural orifice translumenal endoscopic surgery (vNOTES) as a treatment option for ovarian cysts. The objective of this study was to assess the feasibility and safety of employing vNOTES for the management of ovarian cysts., Methods: Our study included women between the ages of 18 and 70 who intended to undergo surgical intervention for benign lesions. Stratified blocked randomization was employed to allocate participants into groups. The main objective was to assess whether the assigned group adhered to the recommended surgical technique for ovarian cystectomy or adnexectomy, without any deviation to alternative surgical methods., Results: A total of 196 patients were included in the study, with all surgeries in each group being conducted according to the assigned procedures. Among them, the ovarian cystectomy layer included 58 cases in the vNOTES group and 58 cases in the conventional laparoscopy (CL) groups. The adnexectomy layer included 40 cases in the vNOTES group and 40 cases in the CL group. Utilizing a sensitivity analysis, the two-sided 95% lower confidence limit was determined to be 5.5% for the disparity in proportions between the vNOTES groups and CL groups. These lower limits fell below the predetermined non-inferiority margin of 10%., Conclusions: The study findings demonstrate that vNOTES was not inferior to CL in terms of adnexectomy or ovarian cystectomy. vNOTES can be considered a more minimally invasive surgical approach, as it results in reduced postoperative pain, faster recovery, and absence of visible incisions. Overall, vNOTES proves to be a safe, feasible, and less invasive treatment option., Trial Registration: This study retrospectively registered with the China Clinical Trial Registry with the registration number ChiCTR2100052223(22-10-2021)., (© 2024. The Author(s).)

The presence of mutations in the BRCA1 gene (MIM: 113705) is widely recognized as a significant genetic predisposition for ovarian cancer. This study investigated the genomic mutations in a Chinese family with a history of ovarian, breast, and rectal adenocarcinoma. A novel germline mutation (Phe1695Val) in BRCA1 was identified through whole-exome sequencing. Subsequently, we performed whole-genome sequencing to identify somatic mutations and analyze mutational signatures in individuals carrying the novel germline mutation. Our findings revealed a correlation between somatic mutational signatures and the BRCA1 germline mutation in the proband with ovarian cancer, while no such association was observed in the tumor tissue from the patient with breast cancer. Furthermore, distinct somatic driver mutations were identified, a truncated mutation in the TP53 gene in the ovarian tumor tissue, and a hotspot mutation in the PIK3CA gene in the breast cancer. According to our findings, the BRCA1 F1695V mutation is linked to ovarian cancer susceptibility in the family and causes specific somatic mutational profiles., (© The Author(s) 2023. Published by Oxford University Press.)

Halogenated Organic Phosphate Esters (OPEs) are commonly found in plasticizers and flame retardants. However, they are one kind of persistent contaminants that can pose a significant threat to human health and ecosystem as new environmental estrogen. In this study, two representative halogenated OPEs, tris(1,3-dichloro-2-propyl) phosphate (TDCP) and tris(2,3-dibromopropyl) phosphate (TDBP), were selected as experimental subjects to investigate their interaction with human serum albumin (HSA). Despite having similar structures, the two ligands exhibited contrasting effects on enzyme activity of HSA, TDCP inhibiting enzyme activity and TDBP activating it. Furthermore, both TDCP and TDBP could bind to HSA at site I, interacted with Arg222 and other residues, and made the conformation of HSA unfolded. Thermodynamic parameters indicated the main driving forces between TDBP and HSA were hydrogen bonding and van der Waals forces, while TDCP was mainly hydrophobic force. Molecular simulations found that more hydrogen bonds of HSA-TDBP formed during the binding process, and the larger charge area of TDBP than TDCP could partially account for the differences observed in their binding abilities to HSA. Notably, the cytotoxicity of TDBP/TDCP was inversely proportional to their binding ability to HSA, implying a new method for determining the cytotoxicity of halogenated OPEs in vitro., 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.)

Nanofibers based on high-performance polymers are much highlighted in recent studies toward advanced lithium-ion batteries. Herein, we demonstrate one scalable poly(ethylene oxide) (PEO)-assisted solution blow spinning strategy for the preparation of heterocyclic aramid (HA) nanofibers of poly( p -phenylene-benzimidazole-terephthalamide). The incorporation of PEO is essential to improve the spinnability of the HA solution achieved directly through the low-temperature-solution copolymerization process. Additionally, the flexible PEO with a strong H-bonding affinity is also utilized as the molecular zipper to adjust the pore size of the nanofiber membrane during the post-treatment process. The obtained membrane combines the good wettability of PEO to the liquid electrolytes, with outstanding mechanical strength, modulus, toughness, and environmental resistance of HA. The nonwoven separator membranes with a porosity of 83.6% exhibited excellent comprehensive performance, which could be seen not only on the high tensile strength (68.2 MPa), modulus (3.0 GPa), and toughness but also on the high thermal stability ( T d > 405 °C) and flame retardancy, as well as the high electrolyte uptake (302.4%). The ion conductivity of the porous separators reached 0.83 mS/cm, with the bulk resistance dropping to 1/4 of the reference polypropylene separator. In the assembly of the Li/LiFePO 4 half battery, the HA separators displayed improved discharge specific capacity and high retention in both rate capability and cycling tests, providing the potential industrial preparation for advanced lithium-ion batteries.

Detecting transportation pipeline leakage points within chemical plants is difficult due to complex pathways, multi-dimensional survey points, and highly dynamic scenarios. However, hexapod robots' maneuverability and adaptability make it an ideal candidate for conducting surveys across different planes. The path-planning problem of hexapod robots in multi-dimensional environments is a significant challenge, especially when identifying suitable transition points and planning shorter paths to reach survey points while traversing multi-level environments. This study proposes a Particle Swarm Optimization (PSO)-guided Double Deep Q-Network (DDQN) approach, namely, the PSO-guided DDQN (PG-DDQN) algorithm, for solving this problem. The proposed algorithm incorporates the PSO algorithm to supplant the traditional random selection strategy, and the data obtained from this guided approach are subsequently employed to train the DDQN neural network. The multi-dimensional random environment is abstracted into localized maps comprising current and next level planes. Comparative experiments were performed with PG-DDQN, standard DQN, and standard DDQN to evaluate the algorithm's performance by using multiple randomly generated localized maps. After testing each iteration, each algorithm obtained the total reward values and completion times. The results demonstrate that PG-DDQN exhibited faster convergence under an equivalent iteration count. Compared with standard DQN and standard DDQN, reductions in path-planning time of at least 33.94% and 42.60%, respectively, were observed, significantly improving the robot's mobility. Finally, the PG-DDQN algorithm was integrated with sensors onto a hexapod robot, and validation was performed through Gazebo simulations and Experiment. The results show that controlling hexapod robots by applying PG-DDQN provides valuable insights for path planning to reach transportation pipeline leakage points within chemical plants.

Microcystins (MCs) are the most common cyanobacterial toxins. Epidemiological investigation showed that exposure to MCs can cause gastro-intestinal symptoms, gastroenteritis and gastric cancer. MCs can also accumulate in and cause histopathological damage to stomach. However, the exact mechanisms by which MCs cause gastric injury were unclear. In this study, Wistar rats were administrated 50, 75 or 100 μg microcystin-LR (MC-LR)/kg, body mass (bm) via tail vein, and histopathology, response of anti-oxidant system and the proteome of gastric tissues at 24 h after exposure were studied. Bleeding of fore-stomach and gastric corpus, inflammation and necrosis in gastric corpus and exfoliation of mucosal epithelial cells in gastric antrum were observed following acute MC-LR exposure. Compared with controls, activities of superoxide dismutase (SOD) were significantly greater in gastric tissues of exposed rats, while activities of catalase (CAT) were less in rats administrated 50 μg MC-LR/kg, bm, and concentrations of glutathione (GSH) and malondialdehyde (MDA) were greater in rats administrated 75 or 100 μg MC-LR/kg, bm. These results indicated that MC-LR could disrupt the anti-oxidant system and cause oxidative stress. The proteomic results revealed that MC-LR could affect expressions of proteins related to cytoskeleton, immune system, gastric functions, and some signaling pathways, including platelet activation, complement and coagulation cascades, and ferroptosis. Quantitative real-time PCR (qRT-PCR) analysis showed that transcriptions of genes for ferroptosis and gastric function were altered, which confirmed results of proteomics. Overall, this study illustrated that MC-LR could induce gastric dysfunction, and ferroptosis might be involved in MC-LR-induced gastric injury. This study provided novel insights into mechanisms of digestive diseases induced by MCs., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Achieving efficient uranium adsorption from highly acidic wastewater is still considered challenging. Here, an inorganic-organic hybridized self-assembly material (rPFE-10) with redox activity was constructed by phytic acid (PA), ethylenediamine (EDA), and Fe(II) via a facile one-pot route, and further applied for U(VI) removal. In the static adsorption experiment, rPFE-10 achieved the maximum U(VI) adsorption capacity of 717.1 mg/g at the optimal pH of 3.5. It also performed preeminently in a highly acidic condition of pH = 1.0, with the highest adsorption capacity of 551.2 mg/g and an equilibrium time of 30 min. Moreover, rPFE-10 exhibited a pH-responsive adsorption selectivity for U(VI) and An-Ln (S (U(VI) ) and S (An-Ln) ), which increased to 69 % and 94 % respectively as pH decreased from 3.0 to 1.0. Additionally, the spectral analysis revealed a reconstruction mechanism induced by multiple synergistic adsorption, in which U(VI) exchange with EDA +/2+ and Fe 2+/3+ and earned suitable coordination geometry and ligand environment to coordinate with PA (mainly P-OH), while partial U(VI) is reduced by Fe(II) in framework. This work not only highlights the facile strategy for enhanced U(VI) retention in highly acidic solution, but expands the potential application of supramolecular self-assembly material in treatment of nuclear wastewater., 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.)

In this study, hawthorn pectin was extracted from dried hawthorn with deep eutectic solvent(DES) and compared with the traditional extraction methods such as acid extraction (AE) and ultrasonic-assisted extraction (UAE). Under optimal conditions, with a molar ratio of choline chloride to urea at 1:3, a water content of 30 %, a liquid-to-solid ratio of 30:1 (mL/g), an extraction temperature of 80 °C, an extraction time of 60 min, and a pH of 1, the yield of hawthorn pectin was 4.33 % ± 0.02 %. The measured results were consistent with the prediction. In addition, compared with AE and UAE, the experimental results showed that DES had a higher yield, a lower degree of esterification, and a slightly different monosaccharide composition from other extraction methods. The results of infrared spectroscopy and scanning electron microscopy showed that DES had a fine microstructure and coarser surface, and the main chemical structure of DES didn't change. The rheological analysis showed that DES had lower apparent viscosity than AE and UAE. These results represent a green source for pectin extraction with high pectin yield and good performance. In conclusion, the deep eutectic solvent has good application prospects in extracting hawthorn pectin., Competing Interests: Declaration of competing interest We declare no financial or other conflicts of interest in our work. This work is an original research and the data presented in manuscript has not been published elsewhere., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The development of a dynamic network for commodity polymer systems via feasible methods has been explored in the context of a society-wide focus on the environment and sustainability. Herein, we demonstrate an adaptive post-curing method used to build a self-healable network of waterborne polyurethane-acrylate (WPUA) composite latex. The composite latex was synthesized via the miniemulsion polymerization of acrylates in the dispersion of waterborne polyurethane (PU), with commercial acetoacetoxyethyl methacrylate (AAEM) serving as the functional monomer. Then, a dynamic disulfide (S-S)-bearing diamine was applied as the crosslinking agent for the post-curing of the hybrid latex via keto-amine condensation, which occurred during the evaporation of water for film formation. It was revealed that the microphase separation in the hybrid films was suppressed by the post-curing network. The mechanical performance exhibited a high reliability as regards the contents of the crosslinking agents. The reversible exchange of S-S bonds meant that the film displayed associative covalent-adaptive networks in the range of medium temperature in stress relaxation tests, and ≥95% recovery in both the stress and the strain was achieved after the cut-off films were self-healed at 70 °C for 2 h. The rebuilding of the network was also illustrated by the >80% recovery in the elongation at break of the films after three crushing-hot pressing cycles. These findings offer valuable insights, not only endowing the traditional WPUA with self-healing and reprocessing properties, but broadening the field of study of dynamic networks to polymer hybrid latex.

Background: Foamy viruses (FVs) are unique nonpathogenic retroviruses, which remain latent in the host for a long time. Therefore, they may be safe, effective gene transfer vectors. In this study, were assessed FV-host cell interactions and the molecular mechanisms underlying FV latent infection., Methods: We used the prototype FV (PFV) to infect HT1080 cells and a PFV indicator cell line (PFVL) to measure virus titers. After 48 h of infection, the culture supernatant (i.e., cell-free PFV particles) and transfected cells (i.e., cell-associated PFV particles) were harvested and incubated with PFVL. After another 48 h, the luciferase activity was used to measure virus titers., Results: Through transcriptomics sequencing, we found that PREB mRNA expression was significantly upregulated. Moreover, PREB overexpression reduced PFV replication, whereas endogenous PREB knockdown increased PFV replication. PREB interacted with the Tas DNA-binding and transcriptional activation domains and interfered with its binding to the PFV long terminal repeat and internal promoter, preventing the recruitment of transcription factors and thereby inhibiting the transactivation function of Tas. PREB C-terminal 329-418 aa played a major role in inhibiting PFV replication; PREB also inhibited bovine FV replication. Therefore, PREB has a broad-spectrum inhibitory effect on FV replication., Conclusions: Our results demonstrated that PREB inhibits PFV replication by impeding its transcription., (© 2023. The Author(s).)

Camptothecin (CPT) and its derivatives have attracted worldwide attention because of their notable anticancer activity. However, the growing demand for CPT in the global pharmaceutical industry has caused a severe shortage of CPT-producing plant resources. In this study, phytochemical analysis of Nothapodytes tomentosa results in the isolation and identification of CPT (13: ) and 16 analogues (1:  - 12, 14:  - 17: ), including a new (1: ) and five known (9, 10, 12, 15: , and 17: ) CPT analogues with an open E-ring. In view of the potential anticancer activity of CPT analogues with an open E-ring, the fragmentation pathways and mass spectra profiles of these six CPT analogues (1, 9, 10, 12, 15: , and 17: ) are investigated, providing a reference for the rapid detection of these compounds in other plants. Furthermore, based on the fragmentation patterns of CPT (13: ) and known analogues (2:  - 8, 11, 14, 16, 18:  - 26: ), the distribution and content of these compounds in different tissues of N. tomentosa, N. nimmoniana, Camptotheca acuminata , and Ophiorrhiza japonica are further studied. Our findings not only provide an alternative plant resource for further expanding the development and utilization of CPT and its analogues, but also lay a foundation for improving the utilization of known CPT-producing plant resources., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Breast cancer was the fourth leading cause of cancer-related death worldwide, and early mammography screening could decrease the breast cancer mortality. Artificial intelligence (AI)-assisted diagnose system based on machine learning (ML) methods can help improve the screening accuracy and efficacy. This study aimed to systematically review and make a meta-analysis on the diagnostic accuracy of mammography diagnosis of breast cancer through various ML methods. Springer Link, Science Direct (Elsevier), IEEE Xplore, PubMed and Web of Science were searched for relevant studies published from January 2000 to September 2021. The study was registered with the PROSPERO International Prospective Register of Systematic Reviews (protocol no. CRD42021284227). A Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used to assess the included studies, and reporting was evaluated using the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). The pooled summary estimates for sensitivity, specificity, the area under the receiver operating characteristic curve (AUC) for three ML methods (convolutional neural network [CNN], artificial neural network [ANN], support vector machine [SVM]) were calculated. A total of 32 studies with 23,804 images were included in the meta-analysis. The overall pooled estimate for sensitivity, specificity and AUC was 0.914 [95% CI 0.868-0.945], 0.916 [95% CI 0.873-0.945] and 0.945 for mammography diagnosis of breast cancer through three ML methods. The pooled sensitivity, specificity and AUC of CNN were 0.961 [95% CI 0.886-0.988], 0.950 [95% CI 0.924-0.967] and 0.974. The pooled sensitivity, specificity and AUC of ANN were 0.837 [95% CI 0.772-0.886], 0.894 [95% CI 0.764-0.957] and 0.881. The pooled sensitivity, specificity and AUC of SVM were 0.889 [95% CI 0.807-0.939], 0.843 [95% CI 0.724-0.916] and 0.913. Machine learning methods (especially CNN) show excellent performance in mammography diagnosis of breast cancer screening based on retrospective studies. More rigorous prospective studies are needed to evaluate the longitudinal performance of AI., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Segmented gamma scanning (SGS) is a fast and effective method for measuring radioactive waste drum. The efficiency calibration is directly related to the accuracy of reconstructed radioactivity. An efficiency function model and SGS efficiency calibration method are proposed for solving existing SGS efficiency calibration problems such as time lag, limited by experimental sources or difficult to effectively combine with SGS system. The SGS system model is established by the Geant4 to calculate the segment efficiency under different linear attenuation coefficients of medium and gamma energies. The efficiency calibration function is established with the function model and parameters. Waste drum samples are constructed with the polyethylene and point sources 137 Cs/ 60 Co to complete SGS experimental measurement, efficiency calibration and radioactivity reconstruction. The result shows that the relative deviation of the reconstructed activity of a single point source at different locations in the drum is -50.48% to 43.69% and it of multi-point sources in a segment or a drum is -27.88% to 3.57%. Experimental results verify the effectiveness of this efficiency function model and SGS calibration method., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Honglong Zheng reports financial support was provided by Key Laboratory of Higher Education of Sichuan Province for Enterprise Informationalization and Internet of Things. Honglong Zheng reports financial support was provided by National Natural Science Foundation Committee of China. Qi Liu reports financial support was provided by Sichuan Provincial Department of Science and Technology of China. Yuhao Li reports financial support was provided by University Student Innovation and Entrepreneurship Training Program of China., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Organophosphate flame retardants (OPFRs) are newly emerging estrogenic environmental pollutants, which attracted widespread public interest owing to their potential threats to human. Here, the interaction between two typical aromatic OPFRs, TPHP/EHDPP and HSA was researched by different experiments. Experimental results indicated that TPHP/EHDPP can insert the site I of HSA and be encircled by several amino acid residues, Asp451, Glu292, Lys195, Trp214 and Arg218 played vital roles in this binding process. At 298 K, the K a value of TPHP-HSA complex was 5.098 × 10 4  M -1 , and the K a value of EHDPP-HSA was 1.912 × 10 4  M -1 . Except H-bonds and van der Waals forces, the π-electrons on the phenyl ring of aromatic-based OPFRs played a pivotal role in maintaining the stability of the complexes. The content alterations of HSA were observed in the present of TPHP/EHDPP. The IC 50 values of TPHP and EHDPP were 157.9 μM and 31.14 μM to GC-2spd cells, respectively. And the existence of HSA has a regulatory effect on the reproductive toxicity of TPHP/EHDPP. In addition, the results of present work implied Ka values of OPFRs and HSA are possible to be a useful parameter for evaluating their relative toxicity., 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.)

Lightweight, flexible, and noncombustible thermo-acoustic insulating (TAI) materials have great potential in vehicles, cold-chain transportation, and aerospace engineering, where weight and space savings are critical. However, the TAI capabilities of many commodities are hindered by the lack of diverse and reasonable resonant cavities with broadband and highly efficient acoustic responsiveness. This study demonstrates a layer-by-layer freeze-casting method for superelastic cellular aerogel construction from varied nanofibers and ice particulates with widely distributed resonant cavities from 0.5 to 300 μm. The method enabled the cumulative freezing of the nanofiber solution from one side to the other side, resulting in vertical pore channels with random holes across the entire freezing distance. The formed cellular networks of stable hinged ternary nanofiber membranes, functionalized as ultrathin nanofiber drums, exhibit strong resonances and efficiently dissipate sound waves in a broad frequency range. A high noise reduction coefficient of 0.65 at a frequency range of 63-6300 Hz and a low thermal conductivity of 0.026 W m -1 K -1 at room temperature was obtained. This work presents the bottom-up fabrication of high-performance TAI aerogels that are beneficial for practical energy-saving devices and buildings and broadband acoustic absorption applications.

Background: Mixed ground-glass lung nodules are a high-risk factor for lung adenocarcinoma. This study aimed to analyze the value of SDCT electron density imaging in the detection of mixed ground-glass lung nodules (GGNs)., Method: 150 patients with GGNs confirmed by chest SDCT and surgical pathology were retrospectively analyzed. GGNs were screened by two senior radiologists by the double-blind method based on conventional CT and SDCT electron density images. Average CT values and electron density (ED) values of GGNs were measured for all, solid and ground-glass., Result: Thirty pGGN cases determined by conventional CT were found to be mGGN on electron density images, including 23 in the invasive adenocarcinoma group (detection rate of 35.38%), which was significantly higher than that of the PGL group (14.89%, P < 0.05). In electron density images, average CT values and ED values in the PGL and invasive adenocarcinoma groups with pGGNs were no difference. The average CT value and ED value were significantly higher in the mGGN invasive adenocarcinoma group compared with the PGL group (P < 0.05). Meanwhile, ROC curve analysis of average CT value and ED value revealed AUC values for mGGN infiltration of 0.759 and 0.752., Conclusion: SDCT can improve GGN visualization and increase the detection rate of mGGN compared with conventional CT. Attention should be paid to invasive adenocarcinoma for lung GGNs detected as mGGNs with high average CT value or ED value., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In view of the nephrotoxicity, hepatotoxicity, and carcinogenicity of aristolochic acids (AAs), the removal of AAs from plants becomes an urgent priority for ensuring the safety of Aristolochia herbal materials. In this study, based on the root-predominant distribution of aristolochic acid I (AAI) in Aristolochia debilis, transcriptome sequencing, in combination with phylogenetic analyses, and gene expression pattern analysis together provided five candidate genes for investigating AAI biosynthesis. Comprehensive in vitro and in vivo enzymatic assays revealed that Ab6OMT1 (6-O-methyltransferase) and AbNMT1 (N-methyltransferase) exhibit promiscuity in substrate recognition, and they could act in a cooperative fashion to achieve conversion of norlaudanosoline, a predicted intermediate in AAI biosynthetic route, into 3'-hydroxy-N-methylcoclaurine through two different methylation reaction sequences. These results shed light on the molecular basis for AAI biosynthesis in Aristolochia herbs. More importantly, Ab6OMT1 and AbNMT1 may be employed as targets for the metabolic engineering of AAI biosynthesis to produce AAs-free Aristolochia herbal materials., 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 GmbH. All rights reserved.)

The enhancement of the heat-dissipation property of polymer-based composites is of great practical interest in modern electronics. Recently, the construction of a three-dimensional (3D) thermal pathway network structure for composites has become an attractive way. However, for most reported high thermal conductive composites, excellent properties are achieved at a high filler loading and the building of a 3D network structure usually requires complex steps, which greatly restrict the large-scale preparation and application of high thermal conductive polymer-based materials. Herein, utilizing the framework-forming characteristic of polymerization-induced para -aramid nanofibers (PANF) and the high thermal conductivity of hexagonal boron nitride nanosheets (BNNS), a 3D-laminated PANF-supported BNNS aerogel was successfully prepared via a simple vacuum-assisted self-stacking method, which could be used as a thermal conductive skeleton for epoxy resin (EP). The obtained PANF-BNNS/EP nanocomposite exhibits a high thermal conductivity of 3.66 W m -1 K -1 at only 13.2 vol % BNNS loading. The effectiveness of the heat conduction path was proved by finite element analysis. The PANF-BNNS/EP nanocomposite shows outstanding practical thermal management capability, excellent thermal stability, low dielectric constant, and dielectric loss, making it a reliable material for electronic packaging applications. This work also offers a potential and promotable strategy for the easy manufacture of 3D anisotropic high-efficiency thermal conductive network structures.