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Factual writing is a key macrogenre of American K-12 schooling that is also valued in workplace and society. This study examined the genre and register features of two subgenres of factual writing—biography and report—composed by 48 sixth-grade students in a curriculum unit on scientists and science-related careers aimed at developing students’ understanding of the nature of science. These texts were analyzed for a range of schematic, lexical, and grammatical features that instantiate the two target genres. Statistical and descriptive analyses revealed that the students demonstrated a fairly mature control over the schematic and lexical features that realize the purpose of either genre and relied heavily on the grammatical resources characteristic of everyday registers in constructing both genres. Additionally, there was a positive relationship between the students’ genre/register familiarity and the holistic quality of their writing, and the students’ reading proficiency was a significant predictor of their genre familiarity and holistic writing quality, but not their register understanding. These findings suggest that learning the grammatical resources characteristic of academic registers remains a major and potentially daunting task for many adolescents.

High performance microwave absorption (MA) materials especially those with tunable frequency are highly desirable for telecommunication industries and military camouflage in the information era. Herein, we constructed hierarchical heterostructures based on VB-group laminated vanadium disulfide (VS2) nanosheets embedded with cobalt tetroxide (Co3O4) nanoparticles. The highly dispersed Co3O4 nanoparticles generate strong electromagnetic coupling networks that could enhance the loss properties of MA materials. Moreover, the interconnected VS2 layered network results in dipolar/interfacial polarization, multiple reflection and scattering favorable for the enhanced MA performance. Impressively, the maximum reflection loss of the VS2/Co3O4 hybrids containing 10% Co3O4 can reach 57.96 dB at a thin thickness of 1.57 mm, and the bandwidth with an RL value less than -10 dB is as large as 3.5 GHz. The effective MA band could be adjusted in a range of 15.1 GHz (2.9-18 GHz) from S to Ku bands by the increase in thickness from 1.2 mm to 5.5 mm. The results show that the synergistic effect of multiple loss mechanisms and good impedance matching could be the reasons for strong MA capability in nearly all frequency bands, and thus, the high-performance and lightweight MA materials could be developed by the VS2/Co3O4 hybrids.

(1) Background: Piglet diarrhea is one of the most serious diseases in pigs and has brought great economic losses to the pig industry. Alteration of the gut microbiota is an important factor in the etiology of piglet diarrhea. Therefore, this study aimed to analyze the differences in the gut microbial structures and fecal metabolic profile between post-weaning diarrhea and healthy Chinese Wannan Black pigs. (2) Methods: An integrated approach of 16S rRNA gene sequencing combined with LC/MS-based metabolomics was employed in this study. (3) Results: We found an increase in the relative abundance of the bacterial genus Campylobacter and a decrease in phylum Bacteroidetes and the species Streptococcus gallolyticus subsp. macedonicus. (S. macedonicus) in piglet diarrhea. Meanwhile, obvious changes in the fecal metabolic profile of diarrheic piglets were also detected, particularly higher levels of polyamines (spermine and spermidine). Moreover, there were substantial associations between the disturbed gut microbiota and the altered fecal metabolites, especially a strong positive relationship between spermidine and Campylobacter. (4) Conclusions: These observations may provide novel insights into potential etiologies related to post-weaning diarrhea and further enhance our understanding of the role of gut microbiota in host homeostasis and in modulating gut microbial structure.

Improper clamping is one of the major causes of part deformation. Improving the fixture arrangement through force analysis of clamping points is an effective means to suppress or improve machining deformation. However, the existing research focuses on the monitoring and off-line optimization of the clamping point force, which has a certain lag on the machining deformation control, and it is difficult to predict the clamping point force due to the time-varying coupling effect of multiple factors such as process parameters, cutting force and clamping point force in the machining process. Inspired by the excellent performance of convolutional neural networks and gated recurrent networks in feature extraction and learning of temporal association laws, this paper proposes a CNN-GRU-based method for predicting the force state of clamping points under variable working conditions. Firstly, a force prediction model of clamping point during milling process with variable working conditions is established. Secondly, a convolutional neural network is designed to extract the features of dynamic coupled machining conditions. Then, a network of gated recurrent units is constructed to learn the temporal correlation law between the machining conditions and the forces on the clamping points to achieve force prediction of the clamping points during machining. Finally, it was verified by the milling process of the piston skirt. The results show that CNN-GRU can effectively predict the clamping force. In addition, CNN-GRU has higher computational efficiency and accuracy compared with CNN-LSTM, CNN-RNN and CNN-BP.

A 3D anisotropic magnetic nanostructure is prepared using a selective assembly approach. Ultrabroad effective absorption bandwidth is achieved by the multi-scale magnetic coupling system we constructed.

Several small-molecule covalent inhibitors of KRAS

CuO supported catalyst with high valence rhenium doping were specially studied for photoelectrocatalytic reduction of CO2 to small molecular alcohols, which were synthesized by nitrate thermal decomposition method on anatase TiO2 nanotube arrays (TiO2-NTs). Photoelectrochemical measurements indicate that the high valence rhenium doping helps in improving the catalytic activity and selectivity of CuO supported catalysts. For the case of 6 wt% Re-doped CuO/TiO2-NTs calcined at 723 K, the principal products are methanol and ethanol with yield up to 19.9 μmol and 7.5 μmol after 5 h photoelectrocatalysis at external potential of −0.4 V under simulated solar illumination. In contrast, the products catalyzed by undoped CuO/TiO2-NTs are only methanol and formaldehyde. These results indicate that the high valence rhenium doping will promote the alcoholization process and benefit the C C coupling, leading to the selective conversion of CO2 to ethanol. Furthermore, under suitable external potential (-0.5 V) the CO2 conversion product is almost entirely composed of ethanol.

Thrombin is an important biomarker for various diseases and biochemical reactions. Rapid and real-time detection of thrombin that quickly neutralizes in early coagulation in the body has gained significant attention for its practical applications. Solution-gated graphene transistors (SGGTs) have been widely studied due to their higher sensitivity and low-cost fabrication for chemical and biological sensing applications. In this paper, the ssDNA aptamer with 29 bases was immobilized on the surface of the gate electrode to specifically recognize thrombin. The SGGT sensor achieved high sensitivity with a limit of detection (LOD) up to fM. The LOD was attributed to the amplification function of SGGTs and the suitable aptamer choice. The ssDNA configuration folding induced by thrombin molecules and the electropositivity of thrombin molecules could arouse the same electrical response of SGGTs, helping the device obtain a high sensitivity. The channel current variation of sensors had a good linear relationship with the logarithm of thrombin concentration in the range of 1 fM to 10 nM. The fabricated device also demonstrated a short response time to thrombin molecules, and the response time to the 1 fM thrombin molecules was about 150 s. In summary, the sensing strategy of aptamer-based SGGTs with high sensitivity and high selectivity has a good prospect in medical diagnosis.

Although VB-Group transition metal disulfides (TMDs) VS2 nanomaterials with specific electronic properties and multiphase microstructures have shown fascinating potential in the field of electromagnetic wave (EMW) absorption, the efficient utilization of VS2 is limited by their environmental instability and sole electromagnetic (EM) loss mechanism. In order to fully exploit the maximal utilization values of VS2 nanomaterials for EMW absorption through mitigating the chemical instability and optimizing the EM parameters, biomass-based glucose derived carbon (GDC) like sugar-coating has been decorated on the surface of stacked VS2 nanosheets via a facile hydrothermal method, followed by high-temperature carbonization. As a result, the modulation of doping amount of glucose injection solution (Glucose) could effectively manipulate the degree of GDC coating on VS2 nanosheets, further implementing the EM response mechanisms of the VS2/GDC hybrids through regulating the conductivity and constructing multi-interface heterostructures, as reflected by the enhanced EMW absorption performance to a great extent. The minimum reflection loss of VS2/GDC hybrids could reach -52.8 dB with a thickness of 2.7 mm at 12.2 GHz. Surprisingly, compared with pristine VS2, the VS2/GDC hybrids have the effective absorption bandwidth (EAB) increased from 2.0 to 5.7 GHz, while their environmental stability is much enhanced because of GDC. Obviously, this work provides a promising candidate to realize frequency band tunability of EMW absorbers with exceptional performance and environmental stability.

Sialic acid (SA) involves multiple different physiological and pathological processes. The SA level in serum is a reliable biomarker for the early diagnosis of malignant tumors. In this study, a new type of solution-gated graphene transistor was designed and fabricated for highly sensitive and real-time detection of SA by rapid binding of boric acid groups to diol monosaccharides. The gate electrode was modified with synthesized carbon quantum dots having boronic acid on the surface as the specific recognition site of SA. The detection of SA is achieved via the change of the gate surface potential after the conjugation of SA with carbon quantum dots. The device sensitivity can reach 10−19 M and a good linear relationship was present between the electrical current response and logarithmic values of the SA concentrations in the range of 10−19 M to 10−5 M. This sensor also exhibited good selectivity and good stability. Furthermore, the detection of SA in simulated serum samples was also carried out and satisfactory results were acquired, showing the high potential of the prepared sensor in clinical application.

Bismuth (Bi) is a scarce and valuable metal, which is associated with copper minerals and condensed in copper electrolyte during electrorefining process. Therefore, the recovery of Bi from the copper electrolyte is of great significance. In this work, barium carbonate (BaCO3) was used to in situ form barium sulfate (BaSO4) and recover Bi(III) from copper electrolyte selectively through coprecipitation method. The concentrations of coexisting ions, such as Cu2+, Ni2+, Sb(III, V), and As(III, V), are relatively stable during the coprecipitation process, indicating a certain selectivity for Bi(III). One-step desorption method was used to extract Bi from the precipitate. The results show that Bi(III) exists in the coprecipitation in two forms; dissolved into the lattice and adsorbed on the surface of BaSO4. The optimized parameters of the coprecipitation process are 25 g L−1 BaCO3, 700 rpm stirring rates, 1000 mg L−1 initial Bi(III) concentration at 60 °C, and the precipitation efficiency of Bi(III) reaches up to 90.4 pct. Besides, the recovery efficiency of Bi(III) reaches up to 99.25 pct under the optimized conditions of 0.5 M HCl solution at 90 °C. Importantly, with the help of a Na2CO3 solution, the recycling of BaCO3 from BaSO4 can be perfectly realized, with a regeneration efficiency of up to 92.53 pct. This work not only clarifies the coprecipitate mechanism of Bi(III) but also provides an effective method to recover Bi from copper electrolyte.

Ti−Fe−xTiC (x=0, 3, 6, 9, wt.%) composites were fabricated through low temperature ball milling of Ti, Fe and TiC powders, followed by spark plasma sintering. The results show that β-Ti, β-Ti−Fe, η-Ti4Fe2O0.4 and TiC particles can be found in the composites. The microstructure can be obviously refined with increasing the content of TiC particles. The coefficient of friction (COF) decreases and the hardness increases with increasing the content of TiC particles. The adhesive wear is the dominant wear mechanism of all the Ti−Fe−xTiC composites. The Ti−Fe−6TiC composite shows the best wear resistance, owing to the small size and high content of TiC particle as well as relatively fine microstructure. The wear rate of the Ti−Fe−6TiC composite is as low as 1.869×10−5 mm3/(N·m) and the COF is only 0.64. Therefore, TiC particle reinforced Ti−Fe based composites may be utilized as potential wear resistant materials.

Monoclonal antibodies targeting the programmed cell death-1/ programmed cell death-ligand 1 (PD-1/PD-L1) immune checkpoint have achieved enormous success in cancer immunotherapy. But the antibody-based immunotherapies carry a number of unavoidable deficiencies such as poor pharmacokinetic properties and immunogenicity. Small-molecule PD-1/PD-L1 inhibitors offer the superiority of complementarity with monoclonal antibodies and represent an appealing alternative. A novel series of isoxazole-containing biphenyl compounds were designed, synthesized and evaluated as PD-1/PD-L1 inhibitors in this paper. The structure–activity relationship of the novel synthesized compounds indicated that the ring-closure strategy of introducing isoxazole could be employed and the 3-cyanobenzyl group was significant for the inhibitory activity against the PD-1/PD-L1 protein–protein interactions. Molecular docking studies were performed to help understand the binding mode of the small-molecule inhibitor with the PD-L1 dimer. In particular, compound II-12 was a promising anti-PD-1/PD-L1 inhibitor with the IC50 value of 23.0 nM, providing valuable information for future drug development.

Rice bran is an important by-product of the milling industry. Arabinoxylan extracted from rice bran (RAX) is available in large quantities and is structurally different from other arabinoxylans from cereals. The anti-obesity effects of RAX and the role of microbiota have not been studied. In this work, we investigated the beneficial effects of RAX in C57BL/6J mice fed a high-fat diet (HFD). We found that supplementation of RAX significantly ameliorated HFD-induced obesity. RAX decreased HFD induced lipid accumulation and regulated genes related to hepatic fatty acid metabolism. Regulated lipid metabolism is associated with reduced systemic inflammation as indicated by TNF-α and IL-6. RAX normalized the gut microbiota and its major metabolites short-chain fatty acids (SCFAs). RAX restored the alpha diversity of the gut microbiota and increased the relative abundance of anti-inflammatory bacteria including

Cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) signaling pathway (cGAS-STING) is a hub linking innate immunity and adaptive immunity against pathogen infection by inducing the production of type I interferon (IFN-I). It also plays pivotal roles in modulating tumorigenesis by ensuring the antigen presentation, T cell priming, activation, and tumor regression. Given its antitumor immune properties, cGAS-STING has attracted intense focus and several STING agonists have entered into clinical trials. However, some problems still exist when activating STING for use in oncological indications. It is remarkable that multiple downstream cytokines such as TNF-α, IL-6 may lead to inflammatory disease and even tumor metastasis in practical trials. Besides, there is a synergistic effect when STING agonists are combined with other immunotherapies. In this review, we discussed the advanced understanding between STING and anti-tumor immunity, as well as a variety of promising clinical treatment strategies.

Arsenic–rhenium filter cake, one of the main wastes produced by copper smelting systems, is a vital source of rhenium (Re). Using traditional hydrometallurgy methods, rhenium can be leached by sulfuric acid solution with the help of oxidants. However, the residual oxidants can seriously affect the efficiency and lifetime of the extractants and ion-exchange resins. We herein propose a novel method to leach rhenium through a displacement reaction using copper sulfate solution, thereby avoiding the use of oxidants. The results show that Re element exists in the arsenic–rhenium filter cake in two forms: Re2S7 and (As,Re)S amorphous. The rhenium leaching efficiency can reach 93.18%, and the kinetic data fit the shrinking core model. The leaching rate is controlled first by chemical reaction, with an apparent activation energy of 78.46 kJ mol−1. Afterwards, the leaching kinetics of rhenium fits an internal diffusion model. The results provide theoretical guidance on how to make full use of waste residues from copper smelting systems.

MoS2/TiO2 composite photocatalysts with visible-light activity were in situ fabricated on titanium substrates via a simple two-step hydrothermal synthesis method, using titanium foil as the Ti source. The structure, morphology, composition and optical properties of the as-prepared photocatalysts were characterized by XRD, SEM, TEM, XPS, UV-vis and PL analyses, respectively. TiO2 exists in the form of nanofibers (NFs), with their length ranging from about 40 nm to 150 nm and a diameter of about 10 nm. MoS2 microspheres are homogeneously dispersed on the surface of TiO2 NFs, forming a MoS2/TiO2 composite. The photocatalytic oxidation rate of NO2− under simulated solar irradiation can reach 62% by the MoS2/TiO2 composite synthesized in a hydrothermal system with a C2H5NS/Na2MoO4 molar ratio of 1 : 0.6 under 200 °C for 24 h, which is much higher than that by pristine TiO2 NFs, P25 and pure MoS2. The photocatalytic oxidation process of NO2− obeys the Langmuir–Hinshelwood kinetic model (pseudo-first order reaction), and the reaction rate constant (k) of the as-prepared composite is about 0.19194 h−1. The presence of MoS2 significantly enhances the visible light absorption of the catalyst, which is conducive to the generation of electrons and holes, thus guaranteeing good photoactivity of the catalyst. The band gap of the composite is about 2.2 eV, indicating the enhanced absorption of visible light. By this simple and low-consumption method, the composite is firmly combined with the titanium substrate, which is convenient for recycling and environmentally friendly implementation.

Mutations to RAS proteins (H-, N-, and K-RAS) are among the most common oncogenic drivers, and tumors harboring these lesions are some of the most difficult to treat. Although covalent small molecules against KRASG12C have shown promising efficacy against lung cancers, traditional barriers remain for drugging the more prevalent KRASG12D and KRASG12V mutants. Targeted degradation has emerged as an attractive alternative approach, but for KRAS, identification of the required high-affinity ligands continues to be a challenge. Another significant hurdle is the discovery of a hybrid molecule that appends an E3 ligase-recruiting moiety in a manner that satisfies the precise geometries required for productive polyubiquitin transfer while maintaining favorable druglike properties. To gain insights into the advantages and feasibility of KRAS targeted degradation, we applied a protein-based degrader (biodegrader) approach. This workflow centers on the intracellular expression of a chimeric protein consisting of a high-affinity target-binding domain fused to an engineered E3 ligase adapter. A series of anti-RAS biodegraders spanning different RAS isoform/nucleotide-state specificities and leveraging different E3 ligases provided definitive evidence for RAS degradability. Further, these established that the functional consequences of KRAS degradation are context dependent. Of broader significance, using the exquisite degradation specificity that biodegraders can possess, we demonstrated how this technology can be applied to answer questions that other approaches cannot. Specifically, application of the GDP-state specific degrader uncovered the relative prevalence of the “off-state” of WT and various KRAS mutants in the cellular context. Finally, if delivery challenges can be addressed, anti-RAS biodegraders will be exciting candidates for clinical development., Biodegraders, engineered proteins that fuse a high-affinity binder (e.g., RBD, K27, R11.1.6, and NS1) to an E3 ligase (e.g., SPOP), prompt degradation of RAS and reveal novel biological insights.

An optimized selective sequential extraction (SSE) procedure was developed to assess the arsenic (As) partitioning in copper slag. The potential As species in copper slag are partitioned into the readily soluble As, dissolvable arsenates, sparingly soluble arsenates, As residing in sulfides, arsenopyrite and metal As, as well as As incorporated into glassy silicates. The inductively coupled plasma atomic emission spectrometry (ICP-AES), scanning electronic microscopy (SEM), transmission electron microscope (TEM), X-ray diffractometry (XRD) and Fourier transform infrared spectroscopy (FTIR) were used to characterize the leachates and residues produced from the operation scheme. The selectivity and recovery of extractants were evaluated through single-phase extraction procedures. Partitioning data of As in slag samples show good agreement with the reported works and the total As recovery of each operation is over 90%. This suggests that the optimized SEE scheme can be reliably employed for As partitioning in As-bearing byproducts from copper smelting.

[Image: see text] Bromodomain-containing protein 4 (Brd4) plays a critical regulatory role in gene transcription that has been recently recognized as a promising strategy for cancer therapy. Based on the BRD4 protein containing two tandem bromodomain structures, BD1 and BD2, we designed and synthesized a series of 3,5-dimethylisoxazole derivative dimers targeting both bromodomains simultaneously to enhance protein binding potency. Among them, compound 22 significantly inhibited the proliferation of colorectal cancer cells HCT116 (IC(50) = 162 nM), with a 20-fold increase in antiproliferative activity compared to inhibitor 14. The results of WesternBlot showed that compound 22 could down-regulate c-MYC protein levels and up-regulate HEXIM1 expression and modulate apoptosis through intrinsic pathways. In addition, compound 22 exhibited outstanding antitumor efficacy in the CT-26 tumor mouse model with a tumor suppression rate of 56.1%. Taken together, 3,5-dimethylisoxazole derivative dimer 22 has remarkable protein inhibitory effect and antitumor activity in vitro and in vivo. A protein binding model of compound 22 is being further analyzed, which will facilitate the development of bivalent BRD4 inhibitors and probe the biological function of BRD4.

SHP2 (Src homology-2 domain-containing protein tyrosine phosphatase-2) is a non-receptor protein tyrosine phosphatase that removes tyrosine phosphorylation. Functionally, SHP2 serves as an important hub to connect several intracellular oncogenic signaling pathways, such as Jak/STAT, PI3K/AKT, RAS/Raf/MAPK, and PD-1/PD-L1 pathways. Mutations and/or overexpression of SHP2 has been associated with genetic developmental diseases and cancers. Because of the role of SHP2 plays in many diseases, the development of inhibitors targeting the catalytic site in SHP2 has been pursued for more than a decade, but none has advanced to clinical development. Recent discovery of allosteric inhibitors has inspired a novel approach to selectively target SHP2 via the noncatalytic site. To date, four SHP2 allosteric inhibitors have entered clinical trials for the treatment of solid tumors. This review will provide a summary of the physiological and biological functions of SHP2 and discuss the development of nonallosteric/allosteric SHP2 inhibitors in recent years.

A practical approach was introduced to study the inclusion mechanism of chlorine in high purity copper electrorefining from nitric acid system via cyclic voltammetry (CV) combined with electrodeposition experiments. The CV curves display an obvious reduction peak of CuCl intermediate, which can provide an insight into the electrochemical behavior of this inclusion. Experimental results show that the increase of HNO3 concentration is favorable to reducing the quantity of chlorine inclusion although there is a slight decline in cathodic current efficiency. The optimum conditions for copper electrorefining in nitric acid system are HNO3 concentration in solution of 1−2 mol/L, moderate temperature of ~35 °C with current density not exceeding 25 mA/cm2. Based on the theoretical studies, an optimized copper electrorefining experiment was designed to simulate the industrial electrolysis, by which high purity copper can be obtained with chlorine inclusion less than 10 μg/g and current efficiency higher than 90%.

Herein, we report a simple approach to synthesize CuFeO2/TNNTs photocathodes composed of high-temperature resistance n-type Nb-doped TiO2 nanotube arrays (TNNTs) and p-type CuFeO2 for CO2 reduction. TNNTs were prepared by anodic oxidation on TiNb alloy sheets and CuFeO2/TNNTs were then prepared by coating precursor liquid onto TNNTs followed by heat treatment in argon atmosphere. The microstructures of CuFeO2/TNNTs and TNNTs before and after heat treatment were investigated by SEM and TEM. The phase compositions of CuFeO2/TNNTs were studied by XRD and XPS, and the light absorption performance were tested by UV–vis diffuse reflectance spectrum. Results show that TNNTs exhibit a regular nanotube arrays structure and this structure is well remained after the calcination at 650 °C. In addition, TNNTs show similar semiconductor properties to n-type TiO2, which enables them to be integrated with p-type CuFeO2 to obtain composite photocathodes with a p-n junction. The synthesized CuFeO2/TNNTs photocathode is well crystallized because no other crystalline iron or copper compounds are included in the prepared photocathode. Furthermore, the photocathode shows high light absorption and fast carrier transport due to the appropriate band gap and p-n junction. As a result, high photoelectrocatalytic CO2 reduction performance with high selectivity to ethanol is obtained on this photocathode.