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In this paper, the reentry phase of the Aerospaceplane is taken as the research object, and the performance parameters of the reusable rocket of a private company are analyzed. Aiming at the guidance and control scheme of the spacecraft returning to the reentry trajectory in the real environment, the original natural algorithm is optimized by considering various reentry flight constraints, and the improved original natural algorithm is used to optimize the reentry trajectory of the Aerospaceplane. We obtained two types of reentry trajectories in the presence of large flight-restricted areas, the "S-type" trajectory and the "spiral-type" trajectory, and obtained data on various influencing factors. The results showed that the basic state parameters of the spiral trajectory optimized using the improved original natural algorithm after adding constraints met the constraint conditions. The aerodynamic heating rate and overload of the spiral reentry trajectory were to some extent greater than those of the S-type trajectory. Under the increasingly stringent requirements of the aerospace environment, new requirements were put forward for the thermal protection system to meet the wider environmental situation. This paper uses the improved original natural algorithm for the first time and applies it to the field of aerospace reentry and entry and adds more constraints to this algorithm for computation. Besides, for the first time, the macroscopic nature of trajectory types is used as a comparative element for parameter comparison, providing a reference basis for selecting trajectory optimization directions from the macroscopic perspective of trajectory types. [ABSTRACT FROM AUTHOR]

Clinical data mining of predictive models offers significant advantages for re-evaluating and leveraging large amounts of complex clinical real-world data and experimental comparison data for tasks such as risk stratification, diagnosis, classification, and survival prediction. However, its translational application is still limited. One challenge is that the proposed clinical requirements and data mining are not synchronized. Additionally, the exotic predictions of data mining are difficult to apply directly in local medical institutions. Hence, it is necessary to incisively review the translational application of clinical data mining, providing an analytical workflow for developing and validating prediction models to ensure the scientific validity of analytic workflows in response to clinical questions. This review systematically revisits the purpose, process, and principles of clinical data mining and discusses the key causes contributing to the detachment from practice and the misuse of model verification in developing predictive models for research. Based on this, we propose a niche-targeting framework of four principles: Clinical Contextual, Subgroup-Oriented, Confounder- and False Positive-Controlled (CSCF), to provide guidance for clinical data mining prior to the model's development in clinical settings. Eventually, it is hoped that this review can help guide future research and develop personalized predictive models to achieve the goal of discovering subgroups with varied remedial benefits or risks and ensuring that precision medicine can deliver its full potential. [ABSTRACT FROM AUTHOR]

Fatty acids from cooking fumes and hypochlorous acid (HOCl) released from indoor cleaning adversely affect respiratory health, but the molecular-level mechanism remains unclear. Here, the effect of cooking oil fumes [palmitic acid (PA), oleic acid (OA), and linoleic acid (LA)] on lung model phospholipid (POPG) hydrochlorination mediated by HOCl at the air–water interface of the hanged droplets was investigated. Interfacial hydrochlorination of POPG was impeded by OA and LA, while that of POPG was facilitated by PA. The effect on POPG hydrochlorination increased with the decrease in oil fume concentration. A potential mechanism with respect to the chain length of these oil fumes, regardless of their saturation, was proposed. PA with a short carbon chain looses the POPG packing and leads to the exposure of the C=C double bonds of POPG, whereas OA and LA with a long carbon chain hinder HOCl from reaching the C=C bonds of POPG. These results for short chain and low concentration dependence suggest that the decay of oil fumes or the conversion of short-chain species by indoor interfacial chemistry might be adverse to lung health. These results provide insights into the relationship between indoor multicomponent pollutants and the respiratory system. [ABSTRACT FROM AUTHOR]

The extensive application of multilayer ceramic capacitors provides an attractive development for terminal electrode pastes. However, the growing requirement for advanced glass materials used in terminal electrode pastes is substantiated. Therefore, to advance the development of electrode pastes, better development and deeper exploration of glass powder are required. Here, a series of BaO–ZnO–B2O3–SiO2 (BZBS) glasses were prepared by melt‐quenching technique, which are used to investigate the effect of the introduction of BaO on structure and properties of the ZnO–B2O3–SiO2 (ZBS) glass. With the introduction of BaO, the relative amount of [BO4] was much less, which made the glass network structure loosen, decreased the glass transition temperature (Tg) and increased the coefficient of thermal expansion of the glass. The decreasing contact angle was observed on the surface of a barium titanate (BaTiO3) substrate. When the BaO content was around 3–7 mol%, the stability of ZBS glass frit could be strengthened by inhibiting the precipitation of Zn2SiO4 crystal. In addition, to further characterize the effect of glass on terminal electrode paste, BZBS glass powder was adopted to prepare copper electrode paste, which was printed on the BaTiO3 substrate and subsequently fired at 800°C for 10 min. With the related copper paste containing ZBS glass doped with 7 mol% BaO, the optimum value of acid resistance and sheet resistance (1.99 mΩ) were exhibited, at which the coated copper paste formed a dense conducting layer. [ABSTRACT FROM AUTHOR]

N -nitrosonornicotine (NNN) and N -nitrosoanabasine (NAB) are both tobacco-specific nitrosamines bearing two heterocyclic amino groups, NAB bearing an extra -CH 2 - group (conferring a hexa- rather than penta-membered cycle) but with significantly decreased carcinogenicity. However, their activating enzymes and related mutagenicity remain unclear. In this study, the chemical-CYP interaction was analyzed by molecular docking, thus the binding energies and conformations of NNN for human CYP2A6, 2A13, 2B6, 2E1 and 3A4 appeared appropriate as a substrate, so did NAB for human CYP1B1, 2A6, 2A13 and 2E1. The micronucleus test in human hepatoma (HepG2) cells with each compound (62.5–1000 μM) exposing for 48 h (two-cell cycle) was negative, however, pretreatment with bisphenol AF (0.1–100 nM, CYPs inducer) and ethanol (0.2% v:v, CYP2E1 inducer) potentiated micronucleus formation by both compounds, while CITCO (1 μM, CYP2B6 inducer) selectively potentiated that by NNN. In C3A cells (endogenous CYPs enhanced over HepG2) both compounds induced micronucleus, which was abolished by 1-aminobenzotriazole (60 μM, CYPs inhibitor) while unaffected by 8-methoxypsoralen (1 μM, CYP2A inhibitor). Consistently, NNN and NAB induced micronucleus in V79-derived recombinant cell lines expressing human CYP2B6/2E1 and CYP1B1/2E1, respectively, while negative in those expressing other CYPs. By immunofluorescent assay both compounds selectively induced centromere-free micronucleus in C3A cells. In PIG-A assays in HepG2 cells NNN and NAB were weakly positive and simply negative, respectively; however, in C3A cells both compounds significantly induced gene mutations, NNN being slight more potent. Conclusively, both NNN and NAB are mutagenic and clastogenic, depending on metabolic activation by partially different CYP enzymes. [Display omitted] • Two tobacco-specific nitrosamines induced genotoxic effect in mammalian cells. • Genotoxicity of NNN was activated by human CYP2B6/2E1, and NAB by CYP1B1/2E1. • Pretreating HepG2 cells with bisphenol AF potentiated the effects of NNN and NAB. • The mode of chromosome damage by NNN and NAB were consistently pure clastogenesis. [ABSTRACT FROM AUTHOR]

Grain production agglomeration (GPA) is the development trend of grain production all over the world, and it is also an important way to promote grain growth and low-carbon development of agriculture. However, in-depth research on whether the GPA can increase the agricultural environmental efficiency and the influencing mechanisms is still lacking. Based on China's provincial data from 1990 to 2019 and the superefficiency DEA model, this study measures the level of GPA and the environmental efficiency of grain production (EEGP) in different grain production functional areas of China. An econometric methods are also used to empirically analyse the impact GPA on the EEGP. The results shows that the level of GPA in China is steadily increasing, and the impact of GPA on EEGP follows a U-shaped trend of initially declining and then rising. China's GPA has exceeded the minimum value of the U-shaped curve and is currently in the stage of promoting the EEGP. Specifically, the level of GPA in China's main grain-producing areas is higher than that in main grain-marketing areas and grain production-marketing balanced areas, and the GPA in main grain-marketing areas and grain production-marketing balanced areas have not yet crossed minimum value of the U-shaped curve. The GPA affects EEGP through farmland scale management and agricultural technology spillover. This study offers a new perspective to explain the changes in China's EEGP, and also provides reference for the EEGP in different regions of the world. [ABSTRACT FROM AUTHOR]

The trend towards multifunctionality and integrating electronic devices has led to the exploration of Y-type hexaferrite with excellent magnetic and dielectric properties. The Y-type hexaferrite BaSrCo 2 Fe 11-x Cr x AlO 22 (0.0 ≤ x ≤ 0.5, with step of 0.1) ceramics have been prepared by conventional solid state reaction route. The phase structure, microscopic morphology, magnetic and dielectric properties of Y-type hexaferrite with chromium substitution are studied in detail. The analysis of XRD, SEM and EDS reveals that the lattice parameters and grain size decrease with the increase of Cr content. XPS results show the coexistence of Fe2+ and Fe3+. All samples exhibit well-defined ferromagnetic hysteresis loops at room temperature and the Cr3+ doping enhances the saturation magnetization and coercivity. The dielectric constants for all samples are found in the range of 10–15 and the dielectric loss is less than 0.02 at high frequency. The resistivity demonstrates that the samples possess high insulating nature with all above 2 × 109 Ω·cm, with a maximum value of 9.5 × 109 Ω·cm for x = 0.2. These results reveal that Cr3+ doped Y type hexaferrite could have potential applications in multifunctional electronic devices. [ABSTRACT FROM AUTHOR]

The electrochemical dinitrogen reduction represents an attractive approach of converting N 2 and water into ammonia, while the rational design of catalytic active centers remains challenging. Investigating model molecular catalysts with well-tuned catalytic sites should help to develop a clear structure-activity relationship for electrochemical N 2 reduction. Herein, we designed several polycyclic aromatic hydrocarbon (PAH) molecules with well-defined positions of boron and nitrogen atoms. Theoretical calculations revealed that the boron atoms possess high local positive charge densities as Lewis acid sites, which are beneficial for N 2 adsorption and activation, thus serving as major catalytic active sites for N 2 electrochemical reduction. Furthermore, the close vicinity of two boron atoms can further enhance the local positive density and subsequent catalytic activity. Using the PAH molecule with two boron atoms separated by two carbon atoms (B-2C-B), a high NH 3 production rate of 34.58 μg·h−1·cm−2 and a corresponding Faradaic efficiency (5.86%) were achieved at −0.7 V versus reversible hydrogen electrode, substantially exceeding the other PAHs with single boron or nitrogen-containing molecular structures. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that the gut microbiome actively regulates cognitive functions and that gut microbiome imbalance is associated with Alzheimer's disease (AD), the most prevalent neurodegenerative disorder. However, the changes in gut microbiome composition in AD and their association with disease pathology, especially in the early stages, are unclear. Here, we compared the profiles of gut microbiota between APP/PS1 transgenic mice (an AD mouse model) and their wild-type littermates at different ages by amplicon-based sequencing of 16S ribosomal RNA genes. Microbiota composition started diverging between the APP/PS1 and wild-type mice at young ages (i.e., 1–3 months), before obvious amyloid deposition and plaque-localized microglial activation in the cerebral cortex in APP/PS1 mice. At later ages (i.e., 6 and 9 months), there were distinct changes in the abundance of inflammation-related bacterial taxa including Escherichia-Shigella, Desulfovibrio, Akkermansia, and Blautia in APP/PS1 mice. These findings suggest that gut microbiota alterations precede the development of key pathological features of AD, including amyloidosis and plaque-localized neuroinflammation. Thus, the investigation of gut microbiota might provide new avenues for developing diagnostic biomarkers and therapeutic targets for AD. [ABSTRACT FROM AUTHOR]

BN‐embedded oligomers with different pairs of BN units were synthesized by electrophilic borylation. Up to four pairs of BN units were incorporated in the large polycyclic aromatic hydrocarbons (PAHs). Their geometric, photophysical, electrochemical, and Lewis acidic properties were investigated by X‐ray crystallography, optical spectroscopy, and cyclic voltammetry. The B−N bonds show delocalized double‐bond characteristics and the conjugation can be extended through the trans‐orientated aromatic azaborine units. Calculations reveal the relatively lower aromaticity for the inner azaborine rings in the BN‐embedded PAH oligomers. The frontier orbitals of the longer oligomers are delocalized over the inner aromatic rings. Consequently, the inner moieties of the BN‐embedded PAH oligomers are more active than the outer parts. This is confirmed by a simple oxidation reaction, which has significant effects on the aromaticity and the intramolecular charge‐transfer interactions. [ABSTRACT FROM AUTHOR]

BN‐embedded oligomers with different pairs of BN units were synthesized by electrophilic borylation. Up to four pairs of BN units were incorporated in the large polycyclic aromatic hydrocarbons (PAHs). Their geometric, photophysical, electrochemical, and Lewis acidic properties were investigated by X‐ray crystallography, optical spectroscopy, and cyclic voltammetry. The B−N bonds show delocalized double‐bond characteristics and the conjugation can be extended through the trans‐orientated aromatic azaborine units. Calculations reveal the relatively lower aromaticity for the inner azaborine rings in the BN‐embedded PAH oligomers. The frontier orbitals of the longer oligomers are delocalized over the inner aromatic rings. Consequently, the inner moieties of the BN‐embedded PAH oligomers are more active than the outer parts. This is confirmed by a simple oxidation reaction, which has significant effects on the aromaticity and the intramolecular charge‐transfer interactions. [ABSTRACT FROM AUTHOR]

A series of polycyclic aromatic hydrocarbons (PAHs), consisting of two pairs of BN units, have been designed and their synthesis has been achieved by electrophilic C−H borylation. Two conjugation extension directions can be found in these B2N2‐embedded PAHs. The B2N2‐containing backbone with shorter effective conjugation length is isoelectronic with diaryl‐fused anthracene, whereas the second derivative, with longer effective conjugation length, is isoelectronic with bis(trans‐arylvinyl)benzene. By incorporating different aryl groups, i.e. furyl, thienyl, benzo[b]furyl, and benzo[b]thienyl groups, into the two crossed directions of the B2N2‐embedded PAHs, their electronic and optical properties have been comparatively investigated by photophysical, electrochemical, and theoretical approaches. It is found that both the substituents and their conjugation extension directions have significant effects on the aromatic and photophysical properties of the B2N2‐embedded PAHs. The conjugation extension in the shorter backbone is more pronounced on the effective conjugation length than the longer backbone. Moreover, all the B2N2‐embedded PAHs behave as both Lewis acids and Lewis bases, and reversible photoluminescence switching can be observed by simply neutralizing the added Lewis acid or Lewis base. [ABSTRACT FROM AUTHOR]

The efficient fixation of excess CO2 from the atmosphere to yield value‐added chemicals remains crucial in response to the increasing levels of carbon emission. Coupling enzymatic reactions with electrochemical regeneration of cofactors is a promising technique for fixing CO2, while producing biomass which can be further transformed into biofuels. Herein, a bioelectrocatalytic system was established by depositing crystallites of a mesoporous metal–organic framework (MOF), termed NU‐1006, containing formate dehydrogenase, on a fluorine‐doped tin oxide glass electrode modified with Cp*Rh(2,2′‐bipyridyl‐5,5′‐dicarboxylic acid)Cl2 complex. This system converts CO2 into formic acid at a rate of 79±3.4 mm h−1 with electrochemical regeneration of the nicotinamide adenine dinucleotide cofactor. The MOF–enzyme composite exhibited significantly higher catalyst stability when subjected to non‐native conditions compared to the free enzyme, doubling the formic acid yield. [ABSTRACT FROM AUTHOR]

The efficient fixation of excess CO2 from the atmosphere to yield value‐added chemicals remains crucial in response to the increasing levels of carbon emission. Coupling enzymatic reactions with electrochemical regeneration of cofactors is a promising technique for fixing CO2, while producing biomass which can be further transformed into biofuels. Herein, a bioelectrocatalytic system was established by depositing crystallites of a mesoporous metal–organic framework (MOF), termed NU‐1006, containing formate dehydrogenase, on a fluorine‐doped tin oxide glass electrode modified with Cp*Rh(2,2′‐bipyridyl‐5,5′‐dicarboxylic acid)Cl2 complex. This system converts CO2 into formic acid at a rate of 79±3.4 mm h−1 with electrochemical regeneration of the nicotinamide adenine dinucleotide cofactor. The MOF–enzyme composite exhibited significantly higher catalyst stability when subjected to non‐native conditions compared to the free enzyme, doubling the formic acid yield. [ABSTRACT FROM AUTHOR]

The RNA synthesis of porcine epidemic diarrhea virus (PEDV) is a sophisticated process performed by a multilingual viral replication complex, together with cellular factors. A key enzyme of this replication complex is RNA-dependent RNA polymerase (RdRp). However, there is limited knowledge about PEDV RdRp. In our present study, a polyclonal antibody against RdRp was prepared by using a prokaryotic expression vector pET-28a-RdRp to study the function of PEDV RdRp and provide a tool to investigate PEDV pathogenesis. In addition, the enzyme activity and half-life of PEDV RdRp were investigated. The result showed that the polyclonal antibody against PEDV RdRp was successfully prepared and was able to be used to detect PEDV RdRp by immunofluorescence and western blotting. Additionally, enzyme activity of PEDV RdRp reached nearly 2 pmol/μg/h and the half-life of PEDV RdRp was 5.47 h. [ABSTRACT FROM AUTHOR]

Two series of regioisomeric luminophores that contained a dithieno[2,3- a:3′,2′- c]phenazine (DTP) unit as an electron acceptor have been designed and synthesized. To investigate the effect of substitution pattern on the optoelectronic properties of these luminophores, electron donors ( N, N-dihexylaniline or N, N-dihexyl-4-vinylaniline) were incorporated at the 2,5-, 8,11-, and 9,10-positions of the DTP unit. We found that the optoelectronic properties of the regioisomeric luminophores were greatly affected by the substitution pattern: functionalization at the 8,11-positions of the DTP unit was superior to the other two substitution patterns in extending the effective π-conjugation and strengthening the intramolecular charge-transfer interactions. Moreover, the insertion of vinyl groups between the DTP and N, N-dihexylaniline units narrowed the energy band-gap for isomers 4 and 5. However, hypsochromically shifted absorption and photoluminescence maxima were observed for isomeric luminophore 6, in which electron donors were substituted at the 2,5-positions of the DTP unit. These results should facilitate greater understanding of the structure-property relationships in regioisomeric semiconductors and present a new way to design optoelectronic materials with effective substitution patterns. [ABSTRACT FROM AUTHOR]

Carbamazepine (CBZ, an antiepileptic) is metabolized by multiple CYP enzymes to its epoxide and hydroxides; however, whether it is genotoxic remains unclear. In this study, molecular docking (CBZ to CYPs) and cytogenotoxic toxicity assays were employed to investigate the activation of CBZ for mutagenic effects, in various mammalian cell models. Docking results indicated that CBZ was valid as a substrate of human CYP2B6 and 2E1, while not for CYP1A1, 1A2, 1B1 or 3A4. In the Chinese hamster (V79) cell line and its derivatives genetically engineered for the expression of human CYP1A1, 1A2, 1B1, 2E1 or 3A4 CBZ (2.5 ~ 40 μM) did not induce micronucleus, while in human CYP2B6-expressing cells CBZ significantly induced micronucleus formation. In a human hepatoma C3A cell line, which endogenously expressed CYP2B6 twofold higher than in HepG2 cells, CBZ induced micronucleus potently, which was blocked by 1-aminobenzotriazole (inhibitor of CYPs) and ticlopidine (specific CYP2B6 inhibitor). In HepG2 cells CBZ did not induce micronucleus; however, pretreatment of the cells with CICTO (CYP2B6 inducer) led to micronucleus formation by CBZ, while rifampicin (CYP3A4 inducer) or PCB126 (CYP1A inducer) did not change the negative results. Immunofluorescent assay showed that CBZ selectively induced centromere-free micronucleus. Moreover, CBZ induced double-strand DNA breaks (γ-H2AX elevation, by Western blot) and PIG-A gene mutations (by flowcytometry) in C3A (threshold being 5 μM, lower than its therapeutic serum concentrations, 17 ~ 51 μM), with no effects in HepG2 cells. Clearly, CBZ may induce clastogenesis and gene mutations at its therapeutic concentrations, human CYP2B6 being a major activating enzyme. [ABSTRACT FROM AUTHOR]

Tetracyclines are a class of antibiotics with a similar four-ringed structure. Due to this structural similarity, they are not easily differentiated from each other. We recently selected aptamers using oxytetracycline as a target and focused on an aptamer named OTC5, which has similar affinities for oxytetracycline (OTC), tetracycline (TC), and doxycycline (DOX). Tetracyclines exhibit an intrinsic fluorescence that is enhanced upon aptamer binding, allowing convenient binding assays and label-free detection. In this study, we analyzed the top 100 sequences from the previous selection library. Three other sequences were found to differentiate between different tetracyclines (OTC, DOX, and TC) by the selective enhancement of their intrinsic fluorescence. Among them, the OTC43 aptamer was more selective for OTC with a limit of detection (LOD) of 0.7 nM OTC, OTC22 was more selective for DOX (LOD 0.4 nM), and OTC2 was more selective for TC (0.3 nM). Using these three aptamers to form a sensor array, principal component analysis was able to discriminate between the three tetracyclines from each other and from the other molecules. This group of aptamers could be useful as probes for the detection of tetracycline antibiotics. [ABSTRACT FROM AUTHOR]

This work describes two new colorimetric methods for smartphone-based point-of-care nanosensing of toxic Ag+ ions. They were based on the analyte-triggered in situ "off–on" of Tyndall effect (TE) of non-plasmonic colloid or plasmonic metal nanoprobes. The first TE-inspired assay (TEA) focused on the initial analytical application of precipitation reactions where a non-plasmonic AgCl colloid could be formed once mixing the analyte with a NaCl solution. Such AgCl colloid displayed strong visual TE signals after their irradiation by a laser pointer pen, which unexpectedly achieved a detection limit of ~ 400 nM. The second TEA was further designed to reduce the limit down to ~ 78 nM using the analyte's oxidizability towards 3,3′,5,5′-tetramethylbenzidine molecules. The redox reaction could create positively charged products that could make negatively charged plasmonic gold nanoparticles aggregate through electrostatic interactions to remarkably amplify their TE responses. Both limits were lower than the minimum allowable Ag+ level (~ 460 nM) in drinking water issued by the World Health Organization. The satisfactory recovery results for detecting Ag+ ions in river, pond, tap, and drinking water additionally demonstrated good selectivity, accuracy and practicality of the proposed methods for potential point-of-need uses in environmental analysis, public health, water safety, etc. [ABSTRACT FROM AUTHOR]

Developing thalamocortical axons traverse the subpallium to reach the cortex located in the pallium. We tested the hypothesis that descending corticofugal axons are important for guiding thalamocortical axons across the pallial-subpallial boundary, using conditional mutagenesis to assess the effects of blocking corticofugal axonal development without disrupting thalamus, subpallium or the pallial-subpallial boundary. We found that thalamic axons still traversed the subpallium in topographic order but did not cross the pallial-subpallial boundary. Co-culture experiments indicated that the inability of thalamic axons to cross the boundary was not explained by mutant cortex developing a long-range chemorepulsive action on thalamic axons. On the contrary, cortex from conditional mutants retained its thalamic axonal growth-promoting activity and continued to express Nrg-1, which is responsible for this stimulatory effect. When mutant cortex was replaced with control cortex, corticofugal efferents were restored and thalamic axons from conditional mutants associated with them and crossed the pallial-subpallial boundary. Our study provides the most compelling evidence to date that cortical efferents are required to guide thalamocortical axons across the pallial-subpallial boundary, which is otherwise hostile to thalamic axons. These results support the hypothesis that thalamic axons grow from subpallium to cortex guided by cortical efferents, with stimulation from diffusible cortical growth-promoting factors. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this study was to outline the fertility features of non-obese diabetic (NOD)/LtSz-scid/scid (NOD/SCID [severe combined immunodeficiency] for short) mice, and to evaluate the effects of NK cell subsets on the pregnancy outcomes of the syngeneic NOD/SCID×NOD/SCID mating combination. Firstly, lymphocyte phenotyping was performed with flow cytometry to confirm the multiple immunodeficits in NOD/SCID mice. Fertility features were assessed in NOD/SCID×NOD/SCID mice and compared with non-immunodeficiency control BALB/c×BALB/c mice. Although the presence of NK cell deficit is apparent in NOD/SCID mice, a certain level of remnant NK activity could be observed in these mice. The remnant NK cell activity was stimulated with polyinosinic-polycytidylic acid (polyIC), or inhibited with anti-asialo GM1 (ASGM1) anti-serum, respectively. The effects of these factors on pregnancy outcomes were evaluated after administration. Roughly normal fertility could be observed in NOD/SCID×NOD/SCID mice. However, a slightly larger sized litter was observed in polyIC-treated NOD/SCID×NOD/SCID mice compared with control NOD/SCID mice. In contrast, embryo resorption was boosted after ASGM1 injection, and correlated subsequently with a smaller litter size. It indicates that the remnant NK cell activity in NOD/SCID mice may be beneficial to feto-maternal tolerance during pregnancy. [Copyright &y& Elsevier]

The ability to generate mutations is a prerequisite to functional genetic analysis. Despite a long history of using mice as a model system for genetic analysis, the scientific community has not generated a comprehensive collection of multiple alleles for most mouse genes. The chemical mutagen of choice for mouse has been N-ethyl-N-nitrosourea (ENU), an alkylating agent that mainly causes base substitutions in DNA, and therefore allows for recovery of complete and partial loss-, as well as gain-, of-function alleles. Specific locus tests designed to detect recessive mutations showed that ENU is the most efficient mutagen in mouse with an approximate mutation rate of 1 in 1,000 gametes,. In fact, several genome-wide and region-specific screens based on phenotypes have been carried out. The anticipation of the completion of the human and mouse genome projects, however, now emphasizes genotype-driven genetics-from sequence to mutants. To take advantage of the mutagenicity of ENU and its ability to create allelic series of mutations, we have developed a complementary approach to generating mutations using mouse embryonic stem (ES) cells. We show that a high mutation frequency can be achieved and that modulating DNA-repair activities can enhance this frequency. The treated cells retain germline competency, thereby rendering this approach applicable for efficient generation of an allelic series of mutations pivotal to a fine-tuned dissection of biological pathways. [ABSTRACT FROM AUTHOR]

Particulate matter (PM) induces and enhances oxidative stress and inflammation, leading to a variety of respiratory diseases, including acute lung injury. Exploring new treatments for PM-induced lung injury has long been of interest to researchers. Palmatine (PAL) is a natural extract derived from plants that has been reported in many studies to alleviate inflammatory diseases. Our study was designed to explore whether PAL can alleviate acute lung injury caused by PM. The acute lung injury model was established by instilling PM (4 mg/kg) into the airway of mice, and PAL (50 mg/kg and 100 m/kg) was administrated orally as the treatment groups. The effect and mechanism of PAL treatment were examined by immunofluorescence, immunohistochemistry, Western Blotting, ELISA, and other experiments. The results showed that oral administration of PAL (50 mg/kg and 100 m/kg) could significantly alleviate lung inflammation and acute lung injury caused by PM. In terms of mechanism, we found that PAL (50 mg/kg) exerts anti-inflammatory and anti-damage effects mainly by enhancing the activation of the Nrf2-related antioxidant pathway and inhibiting the activation of the NLRP3-related pyroptosis pathway in mice. These mechanisms have also been verified in our cell experiments. Further cell experiments showed that PAL may reduce intracellular reactive oxygen species (ROS) by activating Nrf2-related pathways, thereby inhibiting the activation of NLRP3-related pyroptosis pathway induced by PM in Beas-2B cell. Our study suggests that PAL can be a new option for PM-induced acute lung injury. [ABSTRACT FROM AUTHOR]

Exhausted CD8+ T lymphocytes and tumor-associated macrophages play critical roles in determining cancer prognosis and the efficacy of immunotherapy. Our study revealed a negative correlation between exhausted CD8+ T lymphocytes and prognosis in thyroid carcinoma (THCA). Consensus clustering divided patients into two subgroups of exhaustion with different prognoses, as defined by marker genes of exhausted CD8+ T cells. Subsequently, we constructed an eight-gene prognostic signature, and developed a risk score named the exhaustion-related gene score (ERGS) to forecast both prognosis and immunotherapy response in THCA. Bulk RNA sequencing analysis revealed a higher prevalence of M2 macrophages, indicative of an immunosuppressive tumor microenvironment (TME), in the high-ERGS group. Single-cell RNA sequencing showed that SPP1+ macrophages and CD14+ monocytes infiltrations were positively associated with higher ERGS. Functionally, it was determined that SPP1+ macrophages exert an immunosuppressive role, while CD14+ monocytes were implicated in promoting tumor progression and angiogenesis. Analysis of cell–cell interactions between SPP1+ macrophages and T cells highlighted the activation of the SPP1-CD44 and MIF-CD74 axes, both of which could foster an immunosuppressive TME. Therapeutic strategies that target SPP1+ macrophages, CD14+ monocytes, and the SPP1-CD44 and MIF-CD74 axes may potentially improve the prognosis and amplify the immunotherapy response in THCA patients. [ABSTRACT FROM AUTHOR]

Reports on the identification of two bone morphogenetic protein type 1 receptors in drosophila. Decapentaplegic (dpp) receptor; Drosophila protein sequences; Mutant lesions; Properties of Dpp receptor kinases in Drosophila; Experimental procedures.

Tris(2-butoxyethyl) phosphate (TBOEP) is an organophosphorus flame retardant ubiquitously present in the environment and even the human body. TBOEP is toxic in multiple tissues, which forms dealkylated and hydroxylated metabolites under incubation with human hepatic microsomes; however, the impact of TBOEP metabolism on its toxicity, particularly mutagenicity (typically requiring metabolic activation), is left unidentified. In this study, the mutagenicity of TBOEP in human hepatoma cell lines (HepG2 and C3A) and the role of specific CYPs were studied. Through molecular docking, TBOEP bound to human CYP1A1, 1B1, 2B6 and 3A4 with energies and conformations favorable for catalyzing reactions, while the conformations of its binding with human CYP1A2 and 2E1 appeared unfavorable. In C3A cells (endogenous CYPs being substantial), TBOEP exposing for 72 h (2-cell cycle) at low micromolar levels induced micronucleus, which was abolished by 1-aminobenzotriazole (inhibitor of CYPs); in HepG2 cells (CYPs being insufficient) TBOEP did not induce micronucleus, whose effect was however potentiated by pretreating the cells with PCB126 (CYP1A1 inducer) or rifampicin (CYP3A4 inducer). TBOEP induced micronucleus in Chinese hamster V79-derived cell lines genetically engineered for stably expressing human CYP1A1 and 3A4, but not in cells expressing the other CYPs. In C3A cells, TBOEP selectively induced centromere protein B-free micronucleus (visualized by immunofluorescence) and PIG-A gene mutations, and elevated γ-H2AX rather than p-H3 (by Western blot) which indicated specific double-strand DNA breaks. Therefore, this study suggests that TBOEP may induce DNA/chromosome breaks and gene mutations in human cells, which requires metabolic activation by CYPs, primarily CYP1A1 and 3A4. [Display omitted] • Tris(2-butoxyethyl) phosphate (TBOEP) induced DNA breaks and gene mutations. • TBOEP formed micronuclei in human hepatoma C3A cells by a clastogenic mechanism. • Mutagenicity of TBOEP was dependent on metabolic activation by human CYP1A1 and 3A4. • Pretreating HepG2 cells with AhR and PXR activators potentiated the effect of TBOEP. [ABSTRACT FROM AUTHOR]

Chen, Y., 2020. Application of improved Dijkstra algorithm in coastal tourism route planning. In: Gong, D.; Zhang, M., and Liu, R. (eds.), Advances in Coastal Research: Engineering, Industry, Economy, and Sustainable Development. Journal of Coastal Research, Special Issue No. 106, pp. 251–254. Coconut Creek (Florida), ISSN 0749-0208. With the development of computer science and geographic information science, there are more and more applications for GIS. Shortest path analysis is a key issue in GIS geographic network analysis. One of the classical algorithms for calculating the shortest path is the Dijkstra algorithm, which is used in many projects to solve the shortest path problem. However, when the traditional Dijkstra algorithm solves the shortest path between nodes, a large number of nodes outside the identified nodes are calculated, which affects the speed of the algorithm. The Dijkstra algorithm is a classical algorithm for solving the shortest path in the embedded GIS system. By analyzing the Dijkstra algorithm, changing the storage structure, and examining graphing methods, the binary ordering tree algorithm based on the rectangular restricted area reduces the memory storage space. Shortening the query time requires optimizing the shortest path calculation process; the actual data test also shows the effectiveness of the algorithm. [ABSTRACT FROM AUTHOR]

Three functional zones, namely the industrial (IND), the agricultural (AGR), and the grassland (GRA) areas from Inner Mongolia (a remote province in northern China), were selected to evaluate the levels and distributions of PBDEs and the risks posed to local humans. PBDEs concentrations in surface soils and tree bark were detected and the air levels were estimated based on bark measurements. The total concentrations (∑ 8 PBDEs) of BDE-28, -47, −100, −99, −154, −153, −183, and −209 in soils were 1.71–64.9 ng/g dry weight (d.w.), 0.720–4.08 ng/g d.w., and 0.604–3.76 ng/g d.w. in the IND, AGR and GRA areas respectively. The average total concentrations in bark and air were 0.792 ng/g d.w. and 0.125 ng/m³ in the AGR areas respectively, which were lower than those (1.69 ng/g d.w. in the bark and 0.476 ng/m³ in the air) in the IND areas. BDE-209 was the dominant congener, consistent with DeBDE being the dominant commercial products used in China. However, except for BDE-209, BDE-28 and BDE-47 in the AGR and GRA areas averagely contributed about half of the total PBDEs concentrations in soils. BDE-28 concentrations in the bark samples of the AGR areas were significantly higher (p < 0.05) than in the IND areas, and the average total hazard quotients (∑ 8 PBDEs) were higher for humans in the AGR areas (0.12) than in the IND areas (0.08). Degradation of higher-brominated congeners (e.g., BDE-209) and migration of lower-brominated congeners (mainly BDE-28 and BDE-47) may increase the risks to humans in pristine areas. • PBDEs pollution is widespread in Inner Mongolia. • BDE-28 concentrations in bark of AGR areas were significantly higher than in IND areas. • The exposure risk in pristine areas can be higher than in polluted areas due to LRAT of lower-brominated congeners. [ABSTRACT FROM AUTHOR]

This work reports a microwave heating method for synthesis of a VO x /g-C 3 N 4 complex for applications in photocatalytic degradation of rhodamine B (RhB) under visible light illumination. The facile strategy allows the fabrication of the VO x /g-C 3 N 4 composite in 40 min with NH 4 VO 3 and melamine as precursors. A thorough investigation was performed to investigate the structure, morphology, photoabsorption performance and charge separation capability of the VO x /g-C 3 N 4 composite. XRD, FT-IR, XPS and TEM experiments proved that VO x nanoparticles which have the mixed valence state of V5+ and V4+ were dispersed in the g-C 3 N 4. DRS experiment demonstrated that these introduced VO x nanoparticles improved the light absorption property for visible light. N 2 -adsorption analysis showed that the surface area of VO x /g-C 3 N 4 sample was enhanced with increasing VO x content. Although the improved photoabsorpion performance and surface area are beneficial to the photocatalytic RhB degradation, the mostly important reason of the enhanced photoactivity was ascribed to the formed heterojunction structure of g-C 3 N 4 and VO x , which triggers electrons migration via a type-II mechanism and elevates the charge separation. This improved charge separation was confirmed by the PL, EIS, and PC experiments, while the type-II mechanism was verified by reactive species trapping experiment and photocatalytic H 2 evolution test. Due to the improved efficiency in separating charge carriers, the VO x /g-C 3 N 4 worked very well in RhB degradation via photocatalysis. The best VO x /g-C 3 N 4 sample displayed a RhB degradation velocity of 0.079 min−1 under visible light, which is 3.6 folds faster than that of neat g-C 3 N 4. Image 1 • VO x /g-C 3 N 4 was prepared via microwave heating for 40 min. • VO x /g-C 3 N 4 presented much better performance in RhB degradation than g-C 3 N 4. • The improved charge separation was the origin of the high photoactivity. • Type-II mechanism worked in the VO x /g-C 3 N 4 composite. [ABSTRACT FROM AUTHOR]

Here a 1×5 microfluidic optical switch using double drives is proposed. It has a simple structure and ignorable polarization dependent loss. First, the switch with the straight waveguide structure is discussed. Then, various optimization schemes are used, where the oblique waveguide structure and the method of constant refractive index ratio of interface significantly reduce the insertion loss. The final optimization results show that the 1×5 optical switch has smaller insertion loss and crosstalk than general optical switches. For 1550 nm wavelength, the insertion losses of five exit ports are 0.27 dB ∼ 0.47 dB, and the crosstalks are −24.8 dB ∼ −66.5 dB. For 1310 nm wavelength, the insertion losses are 0.13 dB ∼ 0.23 dB, and the crosstalks are −25.6 dB ∼ −70.8 dB. Our work can promote the application of microfluidics in the optical communication and provide a reference for finding waveguide optical switches with low insertion loss. [ABSTRACT FROM AUTHOR]

Background: To summarize evidence of benefits and risks of maternal and neonatal outcomes among pregnant women after Roux-en-Y gastric bypass surgery.Methods: A systematic search was conducted in MEDLINE, EMBASE, Web of Science, Ovid and Cochrane Library until 24th May 2021. Inclusion criteria were randomized trails or observational studies including at least one of maternal or neonatal outcomes from pregnant women who had a history of Roux-en-Y gastric bypass surgery with a control group of pregnant women with no history of bariatric surgery. Non-English studies were excluded. Both fixed-effect and random-effect models were used in the meta-analyses. Newcastle-Ottawa Scale was used to assess quality of studies.Results: Nine retrospective articles were eligible including 13 848  pregnant women with a history of Roux-en-Y gastric bypass surgery and 255 008 pregnant women without a history of bariatric surgery. The results of meta-analysis showed a lower incidence of preterm premature rupture of membranes (OR 0.53, 95% CI [0.47, 0.60], p < 0.00001), large gestational age infants (OR 0.28, 95%CI [0.22, 0.37], p < 0.00001) or macrosomia (OR 0.26, 95%CI [0.23, 0.30], p < 0.00001) in women after Roux-en-Y gastric bypass surgery. On the other hand, infants born to mothers with a history of Roux-en-Y gastric bypass surgery had an increased risk of small gestational age (OR 2.24, 95% CI [1.55, 3.24], p ＜ 0.00001).Conclusion: Roux-en-Y gastric bypass surgery reduces significantly of risks of preterm premature rupture of membranes and large for gestational age/ macrosomia, but increase the risk of small for gestational age. [ABSTRACT FROM AUTHOR]

Porcine epidemic diarrhea virus (PEDV) causes diarrhea, vomiting, and death in piglets. Our previous study has revealed the anti-PEDV activity of Alpiniae oxyphyllae fructus polysaccharide 3 (AOFP3). However, it is still unknown whether AOFP3 can inhibit the replication of PEDV. Therefore, the effect of AOFP3 on PEDV replication was investigated in the present study, along with analysis of viral RdRp activity and expression of hnRNP A1 by RNA polymerase activity assay in vitro, RIP assay, and Western blotting. The results showed that both the PEDV gene and protein levels in IPEC-J2 cells decreased with AOFP3 treatment. In addition, AOFP3 significantly reduced PEDV's replication by down-regulating the activity of PEDV RdRp and reducing the expression of hnRNP A1, whereas only the bind of RdRp to PEDV 3′UTR was inhibited in AOFP3 treated cells. • AOFP3 inhibits PEDV replication in IPEC-J2 cells. • AOFP3 reduces the activity of PEDV RdRp. • AOFP3 reduces the expression of hnRNP A1 in IPEC-J2 cells. • AOFP3 inhibits PEDV RdRp binding to PEDV 3′UTR. [ABSTRACT FROM AUTHOR]

Objectives: Women who had a history of bariatric surgery are increasingly becoming pregnant. There is growing evidence showing that increased risk of postoperative complications may be associated with the gestation after bariatric surgery.The objective of this systematic review was to evaluate the potential impact of pregnancy on weight loss and postoperative complications in obese women after bariatric surgery.Study Design: PubMed, Embase, Medline and Cochrane Central Register of Controlled Trails were searched from inception through October 2018. Selection criteria included observational or randomized trial examining weight loss and medical complications in pregnant compared to non-pregnant women after bariatric surgery. Two reviewers extracted information and performed quality appraisal of eligible articles. Meta-analysis was performed to ascertain the certainty of the evidence when possible.Results: Seven observational cohort studies with a total of 27,369 obese women were included in the final analysis. The mean difference (95 % confidence interval) in percent excess weight loss between pregnant and non-pregnant subjects was -9.5 (-19.9, 0.9). The odds ratio (95 % confidence interval) for postoperative complications in pregnant relative to non-pregnant subjects was 0.85 (0.33, 2.18).Conclusions: Pregnancy may have little or no effect on weight loss or postoperative complications in women who have undergone bariatric surgery. [ABSTRACT FROM AUTHOR]

Graphene and its derivatives, graphene oxide (GO) and graphene oxide quantum dots (GOQDs), have recently attracted much attention as bioactive factors in differentiating stem cells towards osteoblastic lineage. The stem cells from human exfoliated deciduous teeth (SHEDs) possess the properties of self-renewal, extensive proliferation, and multiple differentiation potential, and have gradually become one of the most promising mesenchymal stem cells (MSCs) in bone tissue engineering. The purpose of this study was to explore the effects of GO and GOQDs on the osteogenic differentiation of SHEDs. In this study, GO and GOQDs facilitated SHED proliferation up to 7 days in vitro at the concentration of 1 μg/ml. Because of their excellent fluorescent properties, GOQD uptake by SHEDs was confirmed and distributed in the SHED cytoplasm. Calcium nodules formation, alkaline phosphatase (ALP) activity, and RNA and protein expression increased significantly in SHEDs treated with osteogenic induction medium containing GOQDs but decreased with osteogenic induction medium containing GO. Interestingly, the Wnt/β-catenin signaling pathway appeared to be involved in osteogenic differentiation of SHEDs induced with GOQDs. In summary, GO and GOQDs at the concentration of 1 μg/ml promoted SHED proliferation. GOQDs induced the osteogenic differentiation of SHEDs, whilst GO slightly inhibited it. [ABSTRACT FROM AUTHOR]

To compare the angle of retinal arteries and macular vessel density and foveal avascular zone (FAZ) in early stage familial exudative vitreoretinopathy (FEVR) patients with inner retinal layer (IRL) persistence with FEVR patients without IRL persistence and normal people. This study enrolled 113 early stage FEVR patients and 55 age-matched normal subjects. FEVR patients were divided into IRL group and non-IRL group based on the presence or absence of IRL in fovea. The angle of superior temporal and inferior temporal branch retinal arteries on ultra-wide-field fundus images were measured. Superficial and deep vessel density of whole image, fovea and parafovea, the area and perimeter of FAZ, A-circularity index (AI, perimeter/standard circle perimeter with equal area) and vessel density around the 300-μm width of the FAZ (FD), central macular thickness (CMT) on 3 mm × 3mm OCTA were measured. 30 FEVR patients in IRL group, 83 FEVR patients in non-IRL group, 55 normal people in control group were evaluated. BCVA were worst in IRL group (p <.001). The angle of retinal arteries was smaller in FEVR groups (p <.001) and were smallest in IRL group (p <.001). Superficial and deep vessel density of whole and parafovea area in FEVR patients were significantly lower than that in normal people (p <.05), AI were biggest (p =.01) and FD were smallest in IRL group (p <.001). CMT in IRL group were thicker than non-IRL group and control group (p <.05). Worse BCVA, smaller angle of retinal arteries (more vessels traction), lower macular vessel density, smaller and more irregular FAZ and thicker CMT were observed in FEVR patients with IRL persistence even in early stage. [ABSTRACT FROM AUTHOR]

In-depth research on whether the development of agricultural outsourcing services (AOS) can improve agricultural eco-efficiency (AEE) and the mechanisms underlying the impact of AOS on AEE is still lacking. This study uses micro survey data from Jiangxi Province in China in 2021 to explore the impact of AOS on AEE in terms of farmland scale management and agricultural technology substitution. The results indicate that AOS in general can effectively improve AEE, but this effect varies across the different stages of production. Plough services, fertilizer application services, and pest control services can significantly improve AEE, but seeding services and harvesting services have no significant effect. Farmland scale management and agricultural technology substitution are two effective channels by which AOS improves AEE. The government should improve policies to support AOS, strengthen the positive effects of AOS on AEE, and implement differentiated support policies for AOS related to different production activities. [ABSTRACT FROM AUTHOR]

We introduce a construct called "humanness sensitivity," which we define as the ability to recognize uniquely human characteristics. To evaluate the construct, we used a "concurrent study design" to conduct an internet-based study with a convenience sample of 42,063 people from 88 countries (52.4% from the U.S. and Canada).We sought to determine to what extent people could identify subtle characteristics of human behavior, thinking, emotions, and social relationships which currently distinguish humans from non-human entities such as bots. Many people were surprisingly poor at this task, even when asked simple questions about human relationships or anatomy. Participants were best at identifying subtle aspects of human cognition and worst at identifying subtle aspects of human communication. Test scores were good predictors of whether someone was employed and modest predictors of other self-reported criterion measures. We also found that people identifying themselves in marginal societal categories (e.g., in the "other" category for gender or sexual orientation) identified themselves as less human and also scored lower on our test. As computers continue to become more human-like, our study suggests that the vast majority of humankind will likely have great difficulty distinguishing them from people. Can methods be devised for improving this ability? Might humanness sensitivity help people to make such distinctions? Will people who excel at differentiating humans and non-human entities—like the "blade runners" in the 1982 and 2017 feature films—someday hold a special place in society? [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Mild temperature remarkably enhances the removal of norfloxacin in nZVC/PS process. • The strengthening mechanism is elucidated and clearly presented. • Several key operating variables are thoroughly investigated. • The degradation pathways of norfloxacin by 40 °C/nZVC/PS are clarified. Abstract In this study, mild temperature was applied to enhance norfloxacin (NOR) degradation in nanoscale zero-valent copper (nZVC) activated persulfate (PS) process and the underlying activation mechanism was detailedly elaborated. Results showed that the activation performance of nZVC was far superior than that of micro zero-valent copper (mZVC), and almost complete elimination of 31.32 μM NOR was achieved within only 5 min in the condition of 0.05 g/L nZVC and 1.0 mM PS at 40 °C. The in-situ generated Cu+ was found to be the pivotal active copper species for PS activation and the presence of dissolved oxygen was favorable for its release. Mild temperature not only accelerated the Cu+ release from the nZVC corrision, but provided more opportunity for intermolecular collision to quickly form reactive oxygen species. SO 4 −∙ and ∙OH played the primary role for NOR destruction, while O 2 −· and H 2 O 2 served as the mediators for copper cycling. The higher PS concentration favored NOR removal, whereas overdosing nZVC exerted the negative impact. Further increasing reaction temperature significantly accelerated the elimination of NOR in nZVC/PS process. The satisfactory removal of NOR was achieved under the acidic and neutral conditions. The NOR oxidation in the tested process was found to follow four routes and the cleavage of piperazine ring was determined to be the primary one. These encouraging results demonstrated that mild temperature enhanced nZVC/PS process was a promising strategy for the treatment of refractory and non-biodegradable industrial wastewater. [ABSTRACT FROM AUTHOR]

A correction to the article "Charge Transfer Through Dithieno[2,3-a:3',2'-c]phenazine: Effect of Substitution Pattern on the Optoelectronic Properties of Regioisomeric Luminophores" is presented.

A multifunctional silicon carbide (6H–SiC) material with efficient wicking and evaporative cooling performances in a temperature range of 23–180 °C is created through hierarchical surface nano/microstructuring by a femtosecond laser. The elaborated hierarchical surface structure is an array of nanotextured microgrooves that includes structural features in a range between about 15 nm and 140 μm, integrating benefits from micro- and nanoscale physics of capillarity and thermodynamics. The spatiotemporal dynamics of both water spreading and temperature field obtained by optical and infrared imaging show the excellent wicking and evaporative cooling functionalities of the created material. The range of applications of the developed multifunctional 6H–SiC material includes the technologies for enhancing power generation efficiency, waste heat recovery, and cooling high-heat-flux Si- and SiC-based electronic devices. The application of the created material in cooling technologies for power generation can result in substantial fuel savings and global reduction in greenhouse gas emissions. [ABSTRACT FROM AUTHOR]

In this study, we reviewed the safety and efficacy of botulinum toxin type A (BoNT-A) injection with respect to motor development in children with spastic cerebral palsy aged <2 years. Randomized controlled trials of BoNT-A published between July 1993 and May 2021 were searched in PubMed, WANFANG, CNKI (Chinese National Knowledge Infrastructure), and Cochrane Library Central Register of Controlled Trials using keywords "Botulinum Toxin," "cerebral palsy," "nao xing tan huan," "nao tan," and "rou du du su." The 11-item PEDro Scale was used to rate the quality of all the identified studies. Twelve studies, involving 656 subjects, met the inclusion criteria, and of these, 2 involved patients aged <2 years. Treatment safety was assessed based on adverse event (AE) number and frequency, and efficacy was assessed based on spasticity, range of movement, and motor development. We observed that 3 self-limiting adverse events that were frequently reported included weakness, dysesthesia of the skin, and pain at the injection site. Moreover, there was a significant decrease in the incidence of spasticity and a notable improvement in the range of movement of BoNT-A–treated patients. Therefore, BoNT-A injection shows great safety and efficacy in the treatment of children with cerebral palsy aged <2 years. [ABSTRACT FROM AUTHOR]

A web shell is a backdoor used by hackers to control Web servers and perform privilege escalation, and thus it is crucial to detect web shells effectively. However, the detection of obfuscated web shells has always been a challenge. Inspired by adversarial training methods in the field of computer vision, this paper proposes a generative adversarial network (GAN)-based web shell detection model training framework. Since there has been no method that can generate obfuscated web shells effectively, a generator based on the genetic algorithm, which combines and optimizes the pre-set obfuscation methods, is used to obtain new obfuscation combinations and generate obfuscated samples. The whole proposed framework is named the CWSOGG. When training the detection model, the generator generates web shells that can bypass the discriminator, and the discriminator catches the features of obfuscated samples. Through the adversarial training of the discriminator and generator, the detection model improves its ability to detect obfuscated web shells. To verify the proposed framework is flexible to different models, the discriminator based on four main neural networks has been implemented. Meanwhile, to build complete feature extraction models, both statistical and semantic features are extracted. Due to the lack of web shell data, a clean dataset containing 4,375 web shells is constructed and used to evaluate the CWSOGG. The results have shown that the detection accuracy of each model increases by 86.71% on the generated obfuscated web shells on average and by 7.50% on the simulated real-world obfuscated web shells on average. [ABSTRACT FROM AUTHOR]

As a new-type flame retardant and toxic substance, triphenyl phosphate (TPP) is a ubiquitous pollutant present even in human blood. TPP is transformed by human CYP enzymes to oxidized/dealkylated metabolites. The impact of TPP metabolism on its toxicity, however, remains unclear. In this study, the genotoxicity of TPP in several mammalian cell lines and its relevance to CYP/sulfortransferase (SULT) activities were investigated. The results indicated that TPP induced micronucleus formation at ≥1 μM concentrations in a human hepatoma (C3A, endogenous CYPs being substantial) cell line, which was abolished by 1-aminobenzotriazole (CYPs inhibitor). In cell line HepG2 (parental to C3A with lower CYP expression) TPP was inactive up to 10 μM, while pretreatment with ethanol (CYP2E1 inducer), PCB 126 (CYP1A inducer), or rifampicin (CYP3A inducer) led to micronucleus formation by TPP. In V79-Mz and V79-derived cells expressing human CYP1A1 TPP was inactive (up to 32 μM), and in cells expressing human CYP1B1, 2B6 and 3A4 it induced micronucleus weakly (positive only at 32 μM). However, TPP induced micronucleus potently in V79-derived cells expressing human CYP1A2, while this effect was drastically reduced by human SULT1A1 co-expression; likewise, TPP was inactive in cells expressing both human CYP2E1 and SULT1A1, but became positive with pentachlorophenol (inhibitor of SULT1) co-exposure. Moreover, in C3A cells TPP selectively induced centromere-free micronucleus (immunofluorescent assay), and TPP increased γ-H2AX (by Western blot, indicating double-strand DNA breaks). In conclusion, this study suggests that TPP is potently clastogenic, human CYP1A2 and 2E1 being major activating enzymes while SULT1A1 involved in detoxification. • Triphenyl phosphate (TPP) induced genotoxic effect in mammalian cells. • The genotoxicity of TPP depended on metabolic activation by human CYP enzymes. • Human CYP1A2 and 2E1 were the major metabolic enzymes involved in activating TPP. • The mode of TPP-induced chromosome damage appeared to be purely clastogenesis. [ABSTRACT FROM AUTHOR]

Peripheral nerve injury repair can be enhanced by Schwann cell (SC) transplantation, but clinical applications are limited by the lack of a cell source. Thus, alternative systems for generating SCs are desired. Herein, we found the peripheral blood-derived mesenchymal stem cells (PBMSCs) could be induced into SC like cells with expressing SC-specific markers (S100, P75NTR and CNPase) and functional factors (NGF, NT-3, c-Fos, and Krox20). When the induced PBMSCs (iPBMSCs) were transplanted into crushed rat sciatic nerves, they functioned as SCs by wrapping the injured axons and expressing myelin specific marker of MBP. Furthermore, iPBMSCs seeded in an artificial nerve conduit to bridge a 10-mm defect in a sciatic nerve achieved significant nerve regeneration outcomes, including axonal regeneration and remyelination, nerve conduction recovery, and restoration of motor function, and attenuated myoatrophy and neuromuscular junction degeneration in the target muscle. Overall, the data from this study indicated that PBMSCs can transdifferentiate towards SC-like cells and have potential as grafting cells for nerve tissue engineering. [ABSTRACT FROM AUTHOR]

Background: Islet transplantation is an excellent method for the treatment of type I diabetes mellitus. However, due to the limited number of donors, cumbersome isolation and purification procedures, and immune rejection, the clinical application is greatly limited. The development of a simple and efficient new method to obtain islet β-cells is a key problem that urgently requires a solution for the treatment of type I diabetes mellitus. Methods: In this study, Pbx1, Rfx3, Pdx1, Ngn3, Pax4 and MafA were used to form a six-gene combination to efficiently reprogram aMSCs (adipose mesenchymal stem cells) into ra-βCs (reprogrammed aMSCs-derived islet β-cells), and the characteristics and immunogenicity of ra-βCs were detected. Feasibility of ra-βCs transplantation for the treatment of diabetes mellitus in model dogs and clinical dogs was detected. Results: In this study, aMSCs were efficiently reprogrammed into ra-βCs using a six-gene combination. The ra-βCs showed islet β-cell characteristics. The immunogenicity of ra-βCs was detected and remained low in vitro and increased after transplantation. The cotransplantation of ra-βCs and aMSCs in the treatment of a model and clinical cases of canine diabetes mellitus achieved ideal therapeutic effects. Conclusions: The aMSCs were efficiently reprogrammed into ra-βCs using a six-gene combination. The cotransplantation of ra-βCs and aMSCs as a treatment for canine diabetes is feasible, which provides a theoretical basis and therapeutic method for the treatment of canine diabetes. [ABSTRACT FROM AUTHOR]

Cervical cancer is the most common malignant tumor in the female reproductive system worldwide, and its molecular mechanisms remain complex and poorly understood. Various techniques, including transcriptome sequencing, RT-qPCR, ELISA, immunofluorescence, Western blot, CCK-8 assay, Transwell assay, and xenograft models, were employed to investigate gene/miRNA expression, cellular proliferation, migration, and the interactions between miR-30c-5p, METTL3, and KRAS. Our transcriptome sequencing results demonstrated a significant downregulation of miR-30c-5p in cervical cancer cells. Further investigations using RNA pull-down, dual-luciferase reporter assay, Me-RIP, and PAR-CLIP confirmed METTL3 as one of the downstream targets of miR-30c-5p, while KRAS was identified as an iron-death suppressor gene susceptible to m6A modification. Notably, our Me-RIP analysis demonstrated the involvement of METTL3 in m6A modification of KRAS. In vitro experiments revealed that miR-30c-5p facilitated ferroptosis in cervical cancer cells by inhibiting the METTL3/KRAS axis, thus suppressing proliferation and migration. Additionally, in vivo studies demonstrated that miR-30c-5p repressed the growth and metastasis of cervical cancer xenografts through the inhibition of the METTL3/KRAS axis. Overall, this study highlights the critical role of miR-30c-5p in modulating cervical cancer progression by targeting the METTL3/KRAS axis, providing new insights into the molecular mechanisms underlying cervical cancer growth and metastasis. • This study used transcriptome sequencing to reveal the role of miR-30c-5p in cervical cancer. • This study found that miR-30c-5p targets METTL3 and affects m6A modification. • This study proves the key role of the METTL3/KRAS axis in ferroptosis. • This study reveals the inhibitory effect of miR-30c-5p on the growth of cervical cancer cells. • This study provides new molecular targets for cervical cancer treatment. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the risk factors for bloodstream infection (BSI) caused by extended-spectrum beta-lactamase (ESBL)–producing Escherichia coli (E. coli) and related mortality. The clinical data of 388 patients with E. coli BSI were analyzed. Blood cultures were performed and the antimicrobial susceptibility profiles of the resulting isolates were determined. Four single-nucleotide polymorphisms (rs231775, rs12343816, rs16944, and rs2233406) were genotyped using real-time PCR. ESBL were detected by disk diffusion confirmatory testing. Univariate and multivariate regression analyses were applied to identify the risk factors for ESBL-producing isolates and the BSI-induced mortality. The prevalence of ESBL-producing E. coli in BSI patients was 40.98%. E. coli isolates were commonly susceptible to carbapenem and β-lactam/β-lactamase inhibitor combinations. The major ESBL genes were CTX-M-14, CTX-M-55, CTX-M-15, and CTX-M-27. The proportion of CTX-M-15 was significantly higher in patients over 70 years and those receiving stomach tube catheterization. Nosocomial infection, biliary tract infection, stomach tube catheterization, and previous cephalosporin administration were independent risk factors for ESBL-producing isolates. ESBL positivity, nosocomial infection, and cancer were independent risk factors of mortality. Two genetic polymorphisms associated with inflammation activation, rs231775 A allele and rs2233406 T allele, significantly increased the mortality risk of E. coli BSI with a risk ratio (95% CI) of 1.93 (1.05–3.55) and 4.38 (2.07–9.29), respectively. For patients with nosocomial infection, biliary tract infection, and cancer, the monitor of BSI and antibiotic susceptibility should be enhanced. The invasive procedures should be minimized. rs231775 and rs2233406 are promising prognostic markers for E. coli BSI patients. [ABSTRACT FROM AUTHOR]

Perfluoroalkyl substances (PFASs) are ubiquitous in the environment and even accumulate in the human body associated with their excellent stability and persistence. However, the effect and reaction mechanism at the molecular level on the cell phospholipid peroxidation remained unclear. In this work, the interfacial reaction of model phospholipids (POPG) intervened by per- and polyfluoroalkyl substances (PFASs) at the air-water interface of a hanged droplet exposed to ozone (O 3) was investigated. Perfluorinated carboxylates and sulfonates were evaluated. Four-carbon PFASs promoted interfacial ozonolysis, but PFASs with longer carbon skeletons impeded this chemistry. A model concerning POPG packing was proposed and it was concluded that the interfacial chemistry was mediated by chain length rather than their functional groups. Four-carbon PFASs could couple into POPG ozonolysis by mainly reacting with aldehyde products along with minor Criegee intermediates, but this was not observed for longer PFASs. This is different from that condensed-phase Criegee intermediates preferred to reacting with per-fluoroalkyl carboxylic acids. These results provide insight into the adverse health of PFASs on cell peroxidation. [Display omitted] • PFASs mediating interfacial ozonolysis reactions of model phospholipids (POPG). • Four-carbon PFASs could couple into POPG ozonolysis. • A model on POPG packing for interfacial chemical reactions mediated by chain lengths. • Further insights into the adverse effects of PFASs on cellular peroxidation. [ABSTRACT FROM AUTHOR]