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In 2018, Zhang et al. introduced the Persistent Fault Analysis (PFA) for the first time, which uses statistical features of ciphertexts caused by faulty Sbox to recover the key of block ciphers. However, for most of the variants of PFA, the prior knowledge of the fault (location and value) is required, where the corresponding analysis will get more difficult under the scenario of multiple faults. To bypass such perquisite and improve the analysis efficiency for multiple faults, we propose Chosen-Plaintext based Persistent Fault Analysis (CPPFA). CPPFA introduces chosen-plaintext to facilitate PFA and can reduce the key search space of AES-128 to extremely small. Our proposal requires 256 ciphertexts, while previous state-of-the-art work still requires 1509 and 1448 ciphertexts under 8 and 16 faults, respectively, at the only cost of requiring 256 chosen plaintexts. In particular, CPPFA can be applied to the multiple faults scenarios where all fault locations, values and quantity are unknown, and the worst time complexity of CPPFA is O(28+nf ) for AES-128, where nf represents the number of faults. The experimental results show that when nf > 4, 256 pairs of plaintext-ciphertext can recover the master key of AES-128. As for LED-64, only 16 pairs of plaintext-ciphertext reduce the remaining key search space to 210.

Dendritic cells (DCs), as the most powerful antigen-presenting cells, play a key role in the adaptive immune response, while the defective function of DC is an important factor in immune tolerance to hepatitis B virus (HBV) infection. Hepatitis B virus core antigen (HBcAg) is a highly antigenic protein that can induce a strong antigen-specific immune response against HBV. In this study, we first constructed the ubiquitinated HBcAg gene (UbHBcAg), and then utilized a recombinant lentiviral vector UbHBcAg (LV-UbHBcAg) to explore the role of them in DC autophagy and function. Meanwhile, the effects of autophagy on DC functional activation were further analyzed. Finally, we investigated the underlying mechanism of autophagy induced by LV-UbHBcAg. Results showed that LV-UbHBcAg could promote autophagic progression in DCs, and the upregulated autophagy can further enhance DC functional maturation. In addition, p62 may serve as an important role in autophagy degradation. More importantly, the PI3K/Akt/mTOR signaling pathway was involved in the process of autophagy induced by LV-UbHBcAg. These findings suggest that LV-UbHBcAg can activate DC function by inducing autophagy, which may represent a promising strategy to treat chronic HBV infection.

IntroductionReceptor-like cytoplastic kinases (RLCKs) are known in many plants to be involved in various processes of plant growth and development and regulate plant immunity to pathogen infection. Environmental stimuli such as pathogen infection and drought restrict the crop yield and interfere with plant growth. However, the function of RLCKs in sugarcane remains unclear.Methods and resultsIn this study, a member of the RLCK VII subfamily, ScRIPK, was identified in sugarcane based on sequence similarity to the rice and Arabidopsis RLCKs. ScRIPK was localized to the plasma membrane, as predicted, and the expression of ScRIPK was responsive to polyethylene glycol treatment and Fusarium sacchari infection. Overexpression of ScRIPK in Arabidopsis enhanced drought tolerance and disease susceptibility of seedlings. Moreover, the crystal structure of the ScRIPK kinase domain (ScRIPK KD) and the mutant proteins (ScRIPK-KD K124R and ScRIPK-KD S253A|T254A) were characterized in order to determine the activation mechanism. We also identified ScRIN4 as the interacting protein of ScRIPK.DiscussionOur work identified a RLCK in sugarcane, providing a potential target for sugarcane responses to disease infection and drought, and a structural basis for kinase activation mechanisms.

Electric arc furnace dust (EAFD) is a hazardous by-product of steel production. As global steel output increases, substantial amounts of EAFD are produced, which causes significant environmental issues. EAFD contains amounts of Fe and Zn, which could be reused as raw materials in the steelmaking process. However, zinc oxides can be reduced and vaporized during this process, forming zinc vapor that contaminates equipment surfaces and causes damage. Consequently, various pyrometallurgical methods have been proposed for zinc removal from EAFD. Due to the extensive usage of carbonaceous materials, these methods contribute to significant CO2, raising concerns about greenhouse gas emissions. Microwave heating offers an efficient, energy-saving, and environmentally friendly alternative to pyrometallurgical approaches. EAFD can generate heat under microwave irradiation without carbon addition, which means the CO2 emissions can be reduced by replacing the reductant in the microwave heating process. Furthermore, microwaves enhance zinc removal reactions to a certain extent, resulting in higher efficiency. Thus, employing microwave heating for EAFD processing has significant potential for future development. This paper reviews recent research on using microwave heating for zinc removal from EAFD, focusing on the heating behavior of EAFD in microwaves and the mechanisms of zinc removal. This review will be crucial for researchers working on processing EAFD using microwave heating and could help guide the development of more sustainable and efficient methods.

Background and purpose Tumor recurrence after liver transplantation (LT) impedes the curative chance for hepatocellular carcinoma (HCC) patients. This study aimed to develop a deep pathomics score (DPS) for predicting tumor recurrence after liver transplantation using deep learning. Patients and methods Two datasets of 380 HCC patients who underwent LT were enrolled. Residual convolutional neural networks were used to identify six histological structures of HCC. The individual risk score of each structure and DPS were derived by a modified DeepSurv network. Cox regression analysis and Concordance index were used to evaluate the prognostic significance. The cellular exploration of prognostic immune biomarkers was performed by quantitative and spatial proximity analysis according to three panels of 7-color immunofluorescence. Results The overall classification accuracy of HCC tissue was 97%. At the structural level, immune cells were the most significant tissue category for predicting post-LT recurrence (HR 1.907, 95% CI 1.490–2.440). The C-indices of DPS achieved 0.827 and 0.794 in the training and validation cohorts, respectively. Multivariate analysis for recurrence-free survival (RFS) showed that DPS (HR 4.795, 95% CI 3.017–7.619) was an independent risk factor. Patients in the high-risk subgroup had a shorter RFS, larger tumor diameter and a lower proportion of clear tumor borders. At the cellular level, a higher infiltration of intratumoral NK cells was negatively correlated with recurrence risk. Conclusions This study established an effective DPS. Immune cells were the most significant histological structure related to HCC recurrence. DPS performed well in post-LT recurrence prediction and the identification of clinicopathological features.

In this study, the effect of different carbon sources on the carbothermal reduction of low-grade phosphate ore were examined using FactSage7.2 calculations and vacuum reduction experiments. The thermodynamic calculations showed that the trend of the effect for three types of reducing agents was generally consistent under 1 Pa pressure and 14% carbon dosage. The reduction effect was maximum when graphite was used as the reducing agent, and a maximum mass of P was obtained at 1250 ?C. The vacuum experiment results showed that the reduction and volatilization ratios of phosphate rock increased with temperature for different carbon sources. Maximum reduction ratio was obtained using graphite in the temperature range 1250-1300 ?C. The reduction effect of pulverized coal was optimal at 1350 ?C, when SiO2, Al2O3, and MgO in the pulverized coal ash were exposed to form low-melting eutectics with CaO due to the increased degree of reaction, and the heat and mass transfer rates were increased. At this time, a maximum reduction ratio of 51.77% of the sample and a maximum volatilization ratio of 82.44% of P were achieved. Considering the cost effectiveness, pulverized coal was the optimum carbon source for the treatment of low-grade phosphate rock using vacuum carbothermal reduction.

Bromine radicals derived from photo-induced Csp3–Br bond homolysis can mediate H abstraction/imine radical formation from quinoxalinones and hydrazones, which in turn quench the in situ-generated difluoroalkyl radicals to furnish the products.

Clinicopathological features and correlation of TXNIP expression in PDAC

Primers used in the text.

TXNIP knockdown can reverse the effects of FBW7 overexpressing in vitro.

FBW7 regulates downstream genes in the glycolysis process of pancreatic cancer.

Supplementary Figure legend

Function of TXNIP in pancreatic cancer glucose metabolism and proliferation

Purpose: FBW7 functions as a tumor suppressor by targeting oncoproteins for destruction. We previously reported that the oncogenic mutation of KRAS inhibits the tumor suppressor FBW7 via the Ras–Raf–MEK–ERK pathway, which facilitates the proliferation and survival of pancreatic cancer cells. However, the underlying mechanism by which FBW7 suppresses pancreatic cancer remains unexplored. Here, we sought to elucidate the function of FBW7 in pancreatic cancer glucose metabolism and malignancy.Experimental Design: Combining maximum standardized uptake value (SUVmax), which was obtained preoperatively via a PET/CT scan, with immunohistochemistry staining, we analyzed the correlation between SUVmax and FBW7 expression in pancreatic cancer tissues. The impact of FBW7 on glucose metabolism was further validated in vitro and in vivo. Finally, gene expression profiling was performed to identify core signaling pathways.Results: The expression level of FBW7 was negatively associated with SUVmax in pancreatic cancer patients. FBW7 significantly suppressed glucose metabolism in pancreatic cancer cells in vitro. Using a xenograft model, MicroPET/CT imaging results indicated that FBW7 substantially decreased 18F-fluorodeoxyglucose (18F-FDG) uptake in xenograft tumors. Gene expression profiling data revealed that TXNIP, a negative regulator of metabolic transformation, was a downstream target of FBW7. Mechanistically, we demonstrated that TXNIP was a c-Myc target gene and that FBW7 regulated TXNIP expression in a c-Myc–dependent manner.Conclusions: Our results thus reveal that FBW7 serves as a negative regulator of glucose metabolism through regulation of the c-Myc/TXNIP axis in pancreatic cancer. Clin Cancer Res; 22(15); 3950–60. ©2016 AACR.

Silencing c-Myc impaired glucose metabolism in PDAC cell lines.

Statistical analysis of the correlation between FBW7 and TXNIP.

Hepatocellular carcinoma (HCC) is an immunotherapy-resistant malignancy characterized by high cellular heterogeneity. The diversity of cell types and the interplay between tumor and non-tumor cells remain to be clarified. Single cell RNA sequencing of human and mouse HCC tumors revealed heterogeneity of cancer-associated fibroblast (CAF). Cross-species analysis determined the prominent CD36+ CAFs exhibited high-level lipid metabolism and expression of macrophage migration inhibitory factor (MIF). Lineage-tracing assays showed CD36+CAFs were derived from hepatic stellate cells. Furthermore, CD36 mediated oxidized LDL uptake-dependent MIF expression via lipid peroxidation/p38/CEBPs axis in CD36+ CAFs, which recruited CD33+myeloid-derived suppressor cells (MDSCs) in MIF- and CD74-dependent manner. Co-implantation of CD36+ CAFs with HCC cells promotes HCC progression in vivo. Finally, CD36 inhibitor synergizes with anti-PD-1 immunotherapy by restoring antitumor T-cell responses in HCC. Our work underscores the importance of elucidating the function of specific CAF subset in understanding the interplay between the tumor microenvironment and immune system.

Reducing CO2 into fuels via photochemical reactions relies on highly efficient photocatalytic systems. Herein, we report a new and efficient photocatalytic system for CO2 reduction. Driven by electrostatic attraction, an anionic metal-organic framework Cu-HHTP (HHTP = 2,3,6,7,10,11-hexahydroxytriphenylene) as host and a cationic photosensitizer [Ru(phen)3]2+ (phen = 1,10-phenanthroline) as guest were self-assembled into a photocatalytic system Ru@Cu-HHTP, which showed high activity for photocatalytic CO2 reduction under laboratory light source (CO production rate of 130(5) mmol g-1 h-1, selectivity of 92.9%) or natural sunlight (CO production rate of 69.5 mmol g-1 h-1, selectivity of 91.3%), representing the remarkable photocatalytic CO2 reduction performance. More importantly, the photosensitizer [Ru(phen)3]2+ in Ru@Cu-HHTP is only about 1/500 in quantity reported in the literature. Theoretical calculations and control experiments suggested that the assembly of the catalysts and photosensitizers via electrostatic attraction interactions can provide a better charge transfer efficiency, resulting in high performance for photocatalytic CO2 reduction.

We studied the value of circulating tumor DNA (ctDNA) in predicting early postoperative tumor recurrence and monitoring tumor burden in patients with hepatocellular carcinoma (HCC). Plasma‐free DNA, germline DNA, and tissue DNA were isolated from 41 patients with HCC. Serial ctDNAs were analyzed by next‐generation sequencing before and after operation. Whole‐exome sequencing was used to detect the DNA of HCC and adjacent tissues. In total, 47 gene mutations were identified in the ctDNA of the 41 patients analyzed before surgery. ctDNA was detected in 63.4% and 46% of the patient plasma pre‐ and postoperation, respectively. The preoperative ctDNA positivity rate was significantly lower in the nonrecurrence group than in the recurrence group. With a median follow‐up of 17.7 months, nine patients (22%) experienced tumor recurrence. ctDNA positivity at two time‐points was associated with significantly shorter recurrence‐free survival (RFS). Tumors with NRAS, NEF2L2, and MET mutations had significantly shorter times to recurrence than those without mutations and showed high recurrence prediction performance by machine learning. Multivariate analyses showed that the median variant allele frequency (VAF) of mutations in preoperative ctDNA was a strong independent predictor of RFS. ctDNA is a real‐time monitoring indicator that can accurately reflect tumor burden. The median VAF of baseline ctDNA is a strong independent predictor of RFS in individuals with HCC., Here, we studied the value of circulating tumor DNA (ctDNA), in combination with germline and tissue DNA by whole‐exome sequencing in patients withhepatocellular carcinoma (HCC). Our analysis demonstrated that ctDNA may serve as a real‐time monitoring indicator by accurately reflecting tumor burden, and as a strong independent predictor of recurrence‐free survival in HCC.

IMPORTANCE: Studies of the use of gonadotropin-releasing hormone analogs (GnRHa) to protect ovarian function have shown mixed results. OBJECTIVE: To determine whether administering GnRHa during chemotherapy in premenopausal women with breast cancer can reduce ovarian impairment. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial, conducted at the Shanghai Jiao Tong University Affiliated Shanghai Sixth People’s Hospital and Zhejiang Cancer Hospital in China, was an open-label trial involving premenopausal women aged 18 to 49 years with operable stage I to III breast cancer for which treatment with adjuvant or neoadjuvant cyclophosphamide-containing chemotherapy was planned in 2 parallel groups: treatment with chemotherapy with or without GnRHa. Enrollment occurred from September 2015 to August 2017, and follow-up ended December 2020. The data were analyzed in March 2021. A total of 405 patients were enrolled in the study, among whom 27 patients (6.7%) quit participation voluntarily, 33 (8.1%) did not meet the inclusion criteria and were excluded, and 15 (3.7%) were lost to follow-up. Ultimately 330 patients were included in the primary analysis, including 29 patients with baseline anti-Müllerian hormone levels less than 0.5ng/ mL. INTERVENTIONS: Eligible patients were randomly assigned (1:1) to receive chemotherapy with (n = 165) or without (n = 165) GnRHa. In patients randomized to receive GnRHa, 3.6 mg of goserelin or 3.75 mg of leuprorelin was injected subcutaneously once every 28 days from 1 to 2 weeks before the first cycle of chemotherapy to 4 weeks after the last cycle of chemotherapy. MAIN OUTCOMES AND MEASURES: The primary end point was the rate of premature ovarian insufficiency (POI) at 12 months after chemotherapy. Premature ovarian insufficiency was defined as anti-Müllerian hormone levels of less than 0.5 ng/mL in this study. The secondary end point was overall survival (OS) and tumor-free survival (TFS). RESULTS: A total of 330 eligible patients could be evaluated with complete data, among whom 301 patients (91.2%; GnRHA group: mean [SD] age, 40.6 [6.7] years; control group: mean [SD] age, 40.2 [5.9] years) were eligible for primary end point analysis. At 12 months after the completion of chemotherapy, the POI rate was 10.3% (15 of 146) in the GnRHa group and 44.5% (69 of 155) in the control group (odds ratio, 0.23; 95% CI, 0.14-0.39; P

Lung adenocarcinoma (LUAD) is a malignant tumor of the respiratory system with poor prognosis. Recent studies have revealed that N7-methylguanosine (m7G) methylation is a widespread modification occurring in RNA. But the expression of m7G methylation–related genes in LUAD and their correlations with prognosis are still unclear. In this study, we found 12 m7G methylation–related regulators with differential expression between LUAD and normal lung tissues. According to differentially expressed genes (DEGs), all LUAD cases were separated into two subtypes. The prognostic value of each m7G methylation–related gene for survival was evaluated to construct a multigene signature using The Cancer Genome Atlas (TCGA) cohort. Finally, an m7G methylation–related prognostic signature based on three genes was built to classify LUAD patients into two risk groups. Patients in the high-risk group showed significantly reduced overall survival (OS) when compared with patients in the low-risk group (p < 0.05). The receiver operating characteristic (ROC) curve analysis confirmed the predictive capacity of the signature. The Gene Ontology (GO) functional annotation analysis disclosed that chromosome homeostasis plays an important role in this process. The gene set enrichment analysis (ssGSEA) implied that the immune status was decreased in the high-risk group. To sum up, m7G methylation–related genes play a vital role in tumor immunity and the related signature is a reliable predictor for LUAD prognosis.

A novel N-doped graphene-like carbon nanosheets (CNs) and carbon nanotubes (CNTs)-encapsulated Co-Co3O4 nanoparticles (NPs) (CN@Co-Co3O4/CNTs) were synthesized successfully by a simple hydrothermal and annealing method with graphite carbon nitride (g-C3N4) as self-template. By annealing Co2+/g-C3N4 under N2 atmosphere, g-C3N4 was transformed into CN/CNTs, and Co2+ was reduced into CoNPs which were embedded in CNs. Further annealing in air, a shell of Co3O4 was formed around CoNPs. The amount of CNs, CNTs, and CoNPs can be adjusted by changing the ratio of Co2+ in Co2+/g-C3N4. The graphene-like CNs provided a large number of active sites and a large specific surface area for loading lots of small CoNPs uniformly. The CNTs with a diameter of 100 nm could not only improve the conductivity but also provide a buffer space for the aggregation and volume expansion of Co3O4. CNTs also enlarged the interlayer distance of CNs, which prevented the re-stacking of CNs and provided great convince for the intercalation and de-intercalation of Li+. When applied for anode material of lithium-ion batteries, CN@Co-Co3O4/CNTs exhibited a high discharge capacity of 460.0 mAh g−1 at 5000 mA g−1 after 300 cycles with a Coulombic efficiency of 98% and excellent higher-rate capacity (401.0 mAh g−1 at 2000 mA g−1 and 329.0 mAh g−1 at 5000 mA g−1).

Grain shape and size are key determinants of grain appearance quality and yield in rice. In our previous study, a grain shape QTL, qGS1-35.2, was fine-mapped using near-isogenic lines (NILs) derived from a cross between Zhenshan 97 (ZS97) and Milyang 46 (MY46). One annotated gene, OsPUB3, was found to be the most likely candidate gene. Here, knockout and overexpression experiments were performed to investigate the effects of OsPUB3 on grain shape and size. Four traits were tested, including grain length, grain width, grain weight, and the ratio of grain length to width. Knockout of OsPUB3 in NILZS97, NILMY46, and another rice cultivar carrying the OsPUB3MY46 allele all caused decreases in grain width and weight and increases in the ratio of grain length to width. Results also showed that the magnitude of the mutational effects varied depending on the target allele and the genetic background. Moreover, it was found that NILZS97 and NILMY46 carried different functional alleles of OsPUB3, causing differences in grain shape rather than grain weight. In the overexpression experiment, significant differences between transgenic-positive and transgenic-negative plants were detected in all four traits. These results indicate that OsPUB3 regulates grain shape and size through a complex mechanism and is a good target for deciphering the regulatory network of grain shape. This gene could be used to improve grain appearance quality through molecular breeding as well.

Objective To explore the structural changes and functional changes of the thymus in aging mouse induced by D-galactose, and to explore a suitable method for establishing an aging mouse model of the thymus. Methods Thymus aging mouse models were established, female C57BL/6 mice were randomly divided into control group, [500 mg/(kg.d)] D-galactose treatment group, and [1000 mg/(kg.d)] D-galactose treatment group, with 8 mice in each group. The mice in the D-galactose treatment group were injected with 500 mg/kg and 1000 mg/kg of D-galactose subcutaneously on the back of the neck every day, while the mice in the control group were injected with the same amount of normal saline every day. After 56 days of continuous administration, the mice were sacrificed to take the thymus to observe the gross thymus morphology and calculate the thymus index. Then the thymus structure were observed by HE staining, and CD4/CD8 positive thymocytes were detected by flow cytometry to evaluate the immune function of the thymus. Later, thymus aging mouse models with different treatment time were established. Female C57BL/6 mice were randomly divided into control group and [1000 mg/(kg.d )] D-galactose treatment group, with 24 mice in each group. The mice were sacrificed after 6 weeks, 9 weeks, and 12 weeks treatment. The structure of thymus was observed by HE staining. The contents of thymosin β4, thymosin α1, and thymopoietin in plasma were determined by ELISA. Results D-galactose treatment can induce mouse thymus senescence, atrophy of thymus, decrease of thymus index, disorder of thymus structure and impaired immune function. In the [1000 mg/(kg.d)] D-galactose treatment group, the atrophy of the thymic medulla of mice was more obvious, with the disappeared cortical and medullary boundary, decreased CD4

Grain weight and size, mostly determined by grain length, width and thickness, are crucial traits affecting grain quality and yield in rice. A quantitative trait locus controlling grain length and width in rice, qGS1-35.2, was previously fine-mapped in a 57.7-kb region on the long arm of chromosome 1. In this study, OsPUB3, a gene encoding a U-box E3 ubiquitin ligase, was validated as the causal gene for qGS1-35.2. The effects were confirmed firstly by using CRISPR/Cas9-based mutagenesis and then through transgenic complementation of a Cas9-free knock-out (KO) mutant. Two homozygous KO lines were produced, each having a 1-bp insertion in OsPUB3 which caused frameshift mutation and premature termination. Compared with the recipient and a transgenic-negative control, both mutants showed significant decreases in grain weight and size. In transgenic complementation populations derived from four independent T0 plants, grain weight of transgenic-positive plants was significantly higher than transgenic-negative plants, coming with increased grain length and a less significant decrease in grain width. Based on data documented in RiceVarMap V2.0, eight haplotypes were classified according to six single-nucleotide polymorphisms (SNPs) found in the OsPUB3 coding region of 4695 rice accessions. Significant differences on grain size traits were detected between the three major haplotypes, Hap1, Hap2 and Hap3 that jointly occupy 98.6% of the accessions. Hap3 having the largest grain weight and grain length but intermediate grain width exhibits a potential for simultaneously improving grain yield and quality. In another set of 257 indica rice cultivars tested in our study, Hap1 and Hap2 remained to be the two largest groups. Their differences on grain weight and size were significant in the background of non-functional gse5, but non-significant in the background of functional GSE5, indicating a genetic interaction between OsPUB3 and GSE5. Cloning of OsPUB3 provides a new gene resource for investigating the regulation of grain weight and size.

Since CO