NUDT21 limits CD19 levels through alternative mRNA polyadenylation in B cell acute lymphoblastic leukemia.

B cell progenitor acute lymphoblastic leukemia (B-ALL) treatment has been revolutionized by T cell-based immunotherapies-including chimeric antigen receptor T cell therapy (CAR-T) and the bispecific T cell engager therapeutic, blinatumomab-targeting surface glycoprotein CD19. Unfortunately, many patients with B-ALL will fail immunotherapy due to 'antigen escape'-the loss or absence of leukemic CD19 targeted by anti-leukemic T cells. In the present study, we utilized a genome-wide CRISPR-Cas9 screening approach to identify modulators of CD19 abundance on human B-ALL blasts. These studies identified a critical role for the transcriptional activator ZNF143 in CD19 promoter activation. Conversely, the RNA-binding protein, NUDT21, limited expression of CD19 by regulating CD19 messenger RNA polyadenylation and stability. NUDT21 deletion in B-ALL cells increased the expression of CD19 and the sensitivity to CD19-specific CAR-T and blinatumomab. In human B-ALL patients treated with CAR-T and blinatumomab, upregulation of NUDT21 mRNA coincided with CD19 loss at disease relapse. Together, these studies identify new CD19 modulators in human B-ALL.

Genomic determinants of response and resistance to inotuzumab ozogamicin in B-cell ALL.

ABSTRACT: Inotuzumab ozogamicin (InO) is an antibody-drug conjugate that delivers calicheamicin to CD22-expressing cells. In a retrospective cohort of InO-treated patients with B-cell acute lymphoblastic leukemia, we sought to understand the genomic determinants of the response and resistance to InO. Pre- and post-InO-treated patient samples were analyzed by whole genome, exome, and/or transcriptome sequencing. Acquired CD22 mutations were observed in 11% (3/27) of post-InO-relapsed tumor samples, but not in refractory samples (0/16). There were multiple CD22 mutations per sample and the mechanisms of CD22 escape included epitope loss (protein truncation and destabilization) and epitope alteration. Two CD22 mutant cases were post-InO hyper-mutators resulting from error-prone DNA damage repair (nonhomologous/alternative end-joining repair, or mismatch repair deficiency), suggesting that hypermutation drove escape from CD22-directed therapy. CD22-mutant relapses occurred after InO and subsequent hematopoietic stem cell transplantation (HSCT), suggesting that InO eliminated the predominant clones, leaving subclones with acquired CD22 mutations that conferred resistance to InO and subsequently expanded. Acquired loss-of-function mutations in TP53, ATM, and CDKN2A were observed, consistent with a compromise of the G1/S DNA damage checkpoint as a mechanism for evading InO-induced apoptosis. Genome-wide CRISPR/Cas9 screening of cell lines identified DNTT (terminal deoxynucleotidyl transferase) loss as a marker of InO resistance. In conclusion, genetic alterations modulating CD22 expression and DNA damage response influence InO efficacy. Our findings highlight the importance of defining the basis of CD22 escape and eradication of residual disease before HSCT. The identified mechanisms of escape from CD22-targeted therapy extend beyond antigen loss and provide opportunities to improve therapeutic approaches and overcome resistance. These trials were registered at www.ClinicalTrials.gov as NCT01134575, NCT01371630, and NCT03441061.

Enhancer retargeting of CDX2 and UBTF::ATXN7L3 define a subtype of high-risk B-progenitor acute lymphoblastic leukemia.

Transcriptome sequencing has identified multiple subtypes of B-progenitor acute lymphoblastic leukemia (B-ALL) of prognostic significance, but a minority of cases lack a known genetic driver. Here, we used integrated whole-genome (WGS) and -transcriptome sequencing (RNA-seq), enhancer mapping, and chromatin topology analysis to identify previously unrecognized genomic drivers in B-ALL. Newly diagnosed (n = 3221) and relapsed (n = 177) B-ALL cases with tumor RNA-seq were studied. WGS was performed to detect mutations, structural variants, and copy number alterations. Integrated analysis of histone 3 lysine 27 acetylation and chromatin looping was performed using HiChIP. We identified a subset of 17 newly diagnosed and 5 relapsed B-ALL cases with a distinct gene expression profile and 2 universal and unique genomic alterations resulting from aberrant recombination-activating gene activation: a focal deletion downstream of PAN3 at 13q12.2 resulting in CDX2 deregulation by the PAN3 enhancer and a focal deletion of exons 18-21 of UBTF at 17q21.31 resulting in a chimeric fusion, UBTF::ATXN7L3. A subset of cases also had rearrangement and increased expression of the PAX5 gene, which is otherwise uncommon in B-ALL. Patients were more commonly female and young adult with median age 35 (range,12-70 years). The immunophenotype was characterized by CD10 negativity and immunoglobulin M positivity. Among 16 patients with known clinical response, 9 (56.3%) had high-risk features including relapse (n = 4) or minimal residual disease >1% at the end of remission induction (n = 5). CDX2-deregulated, UBTF::ATXN7L3 rearranged (CDX2/UBTF) B-ALL is a high-risk subtype of leukemia in young adults for which novel therapeutic approaches are required.

Bioactive sulforaphane from cruciferous vegetables: advances in biosynthesis, metabolism, bioavailability, delivery, health benefits, and applications.

Chronic inflammation-induced diseases (CID) are the dominant cause of death worldwide, contributing to over half of all global deaths. Sulforaphane (SFN) derived from cruciferous vegetables has been extensively studied for its multiple functional benefits in alleviating CID. This work comprehensively reviewed the biosynthesis, metabolism, bioavailability, delivery, health benefits, and applications of SFN and its potential mechanisms against CID (e.g., cancer, obesity, type 2 diabetes, et al.), and neurological disorders based on a decade of research. SFN exerts its biological functions through the hydrolysis of glucosinolates by gut microbiota, and exhibits rapid metabolism and excretion characteristics via metabolization of mercapturic acid pathway. Microencapsulation is an important way to improve the stability and targeted delivery of SFN. The health benefits of SNF against CID are attributed to the multiple regulatory mechanisms including modulating oxidative stress, inflammation, apoptosis, immune response, and intestinal homeostasis. The clinical applications of SFN and related formulations show promising potential; however, further exploration is required regarding the sources, dosages, toxicity profiles, and stability of SFN. Together, SFN is a natural product with great potential for development and application, which is crucial for the development of functional food and pharmaceutical industries.

Enhancing the Electrochemiluminescence of Porphyrin via Crystalline Networks of Metal-Organic Frameworks for Sensitive Detection of Cardiac Troponin I.

Porphyrins easily aggregate due to unfavorable π-π accumulation, causing luminescent quenching in the aqueous phase and subsequently reducing luminescent efficiency. It is a feasible way to immobilize porphyrin molecules through metal-organic framework materials (MOFs). In this study, 5,10,15,20-tetrakis (4-carboxyphenyl) porphyrin (TCPP) was introduced into the metal-organic skeleton (PCN-224) as a ligand. The result showed that the electrochemiluminescence (ECL) and photoluminescence (PL) efficiency of the MOF skeleton was 8.2 and 6.5 times higher than TCPP, respectively. Impressively, the periodic distribution of porphyrin molecules in the MOF framework can overcome the bottleneck of porphyrin aggregation, resulting in the organic ligand TCPP participating in the electron transfer reaction. Herein, based on the PCN-224, a sandwich-type ECL immunosensor was constructed for the determination of cardiac troponin I (cTnI). It provided sensitive detection of cTnI in the range of 1 fg/mL to 10 ng/mL with a detection limit of 0.34 fg/mL. This work not only innovatively exploited a disaggregation ECL (DIECL) strategy via the crystalline framework of MOF to enhance the PL and ECL efficiency of porphyrin but also provided a promising ECL platform for the ultrasensitive monitoring of cTnI.

Viscosity-Responsive Electrochemiluminescence of Diphenylbenzofulvene Derivatives.

The development of superior probes is highly desirable and valuable for viscosity measurement. Herein, we designed and reported a series of diphenylbenzofulvene (DPBF)-based organic luminophores according to the molecular regulation strategy. There are two free-rotating phenyl groups attached to the rigid fluorene skeleton in the DPBF, enabling its unique propeller-like noncoplanar chemical structure. Benefiting from this, DPBFs could feature outstanding PL and ECL emissions with intriguing aggregation-induced characteristics. Experimental and theoretical investigations revealed that substituent, spatial structure, and molecular orbital energy profoundly affected their luminescent behaviors. It was disclosed that fluoro-substituted DPBF(F)2 with a smaller LUMO-HOMO band gap demonstrated the strongest ECL emission and was selected as the optimal ECL emitter. Finally, DPBF(F)2 featured a linear response to the viscosity and VC content with lower limits of detection (LOD) of 5.69 µcP and 38.2 nM, respectively. This study represents the first example of the ECL probe toward viscosity and will be of great significance for both ECL application and viscosity measurement.

Intelligent sort-timing prediction for image-activated cell sorting.

Intelligent image-activated cell sorting (iIACS) has enabled high-throughput image-based sorting of single cells with artificial intelligence (AI) algorithms. This AI-on-a-chip technology combines fluorescence microscopy, AI-based image processing, sort-timing prediction, and cell sorting. Sort-timing prediction is particularly essential due to the latency on the order of milliseconds between image acquisition and sort actuation, during which image processing is performed. The long latency amplifies the effects of the fluctuations in the flow speed of cells, leading to fluctuation and uncertainty in the arrival time of cells at the sort point on the microfluidic chip. To compensate for this fluctuation, iIACS measures the flow speed of each cell upstream, predicts the arrival timing of the cell at the sort point, and activates the actuation of the cell sorter appropriately. Here, we propose and demonstrate a machine learning technique to increase the accuracy of the sort-timing prediction that would allow for the improvement of sort event rate, yield, and purity. Specifically, we trained an algorithm to predict the sort timing for morphologically heterogeneous budding yeast cells. The algorithm we developed used cell morphology, position, and flow speed as inputs for prediction and achieved 41.5% lower prediction error compared to the previously employed method based solely on flow speed. As a result, our technique would allow for an increase in the sort event rate of iIACS by a factor of ~2.

Role of the bovine PRAMEY protein in sperm function during in vitro fertilization (IVF).

Preferentially expressed antigen in melanoma (PRAME) is a cancer/testis antigen (CTA) that is predominantly expressed in normal male gonad tissues and a variety of tumors. PRAME proteins are present in the acrosome and sperm tail, but their role in sperm function is unknown. The objective of this study was to examine the function of the bovine Y-linked PRAME (PRAMEY) during spermatozoal capacitation, the acrosome reaction (AR), and fertilization. Freshly ejaculated spermatozoa were induced to capacitate and undergo AR in vitro. Western blotting results revealed a decrease in the PRAMEY protein in capacitated spermatozoa, and the release of the PRAMEY protein from the acrosome during the AR, suggesting its involvement in sperm capacitation and AR. IVF was performed using in vitro matured bovine oocytes and cauda epididymal spermatozoa either treated with PRAMEY antibody, rabbit IgG, or DPBS. Sperm-egg binding and early embryos were examined at 6 and 45 h post IVF, respectively. The number of spermatozoa that bound per oocyte was nearly two-fold greater in the PRAMEY antibody treatment group (34.4) when compared to both the rabbit IgG (17.6) and DPBS (18.1) controls (P < 0.01). Polyspermy rate in the antibody-treated group (18.9%) was three-fold greater than the rabbit IgG control (6.0%) (P < 0.01). The results indicate that PRAMEY may play a role in anti-polyspermy defense. This study thus provides the initial evidence for the involvement of the PRAME protein family in sperm function and fertilization.

A leucine-rich repeat receptor kinase gene confers quantitative susceptibility to maize southern leaf blight.

Southern leaf blight (SLB), caused by the necrotrophic fungal pathogen Cochliobolus heterostrophus (anamorph Bipolaris maydis), is a major foliar disease which causes significant yield losses in maize worldwide. A major quantitative trait locus, qSLB3.04 , conferring recessive resistance to SLB was previously mapped on maize chromosome 3. Using a combination of map-based cloning, association analysis, ethyl methanesulfonate and transposon mutagenesis, and CRISPR-Cas9 editing, we demonstrate that a leucine-rich repeat receptor-like kinase gene which we have called ChSK1 (Cochliobolus heterostrophus Susceptibility Kinase 1) at qSLB3.04 causes increased susceptibility to SLB. Genes of this type have generally been associated with the defense response. We present evidence that ChSK1 may be associated with suppression of the basal immune response. These findings contribute to our understanding of plant disease susceptibility genes and the potential to use them for engineering durable disease resistance.

Tumor-intrinsic and -extrinsic determinants of response to blinatumomab in adults with B-ALL.

Blinatumomab, a bispecific antibody that directs CD3+ T cells to CD19+ tumor cells, shows variable efficacy in B-progenitor acute lymphoblastic leukemia (B-ALL). To determine tumor-intrinsic and -extrinsic determinants of response, we studied 44 adults with relapsed or refractory B-ALL (including 2 minimal residual disease positive) treated with blinatumomab using bulk tumor and single-cell sequencing. The overall response rate in patients with hematological disease was 55%, with a high response rate in those with CRLF2-rearranged Philadelphia chromosome-like ALL (12 [75%] of 16). Pretreatment samples of responders exhibited a tumor-intrinsic transcriptomic signature of heightened immune response. Multiple mechanisms resulted in loss of CD19 expression, including CD19 mutations, CD19-mutant allele-specific expression, low CD19 RNA expression, and mutations in CD19 signaling complex member CD81. Patients with low hypodiploid ALL were prone to CD19- relapse resulting from aneuploidy-mediated loss of the nonmutated CD19 allele. Increased expression of a CD19 isoform with intraexonic splicing of exon 2, CD19 ex2part, at baseline or during therapy was associated with treatment failure. These analyses demonstrate both tumor-intrinsic and -extrinsic factors influence blinatumomab response. We show that CD19 mutations are commonly detected in CD19- relapse during blinatumomab treatment. Identification of the CD19 ex2part splice variant represents a new biomarker predictive of blinatumomab therapy failure.

Effects of SO2 on NH4NO3 Photolysis: The Role of Reducibility and Acidic Products.

Nitrate photolysis is a vital process in secondary NOx release into the atmosphere. The heterogeneous oxidation of SO2 due to nitrate photolysis has been widely reported, while the influence of SO2 on nitrate photolysis has rarely been investigated. In this study, the photolysis of nitrate on different substrates was investigated in the absence and presence of SO2. In the photolysis of NH4NO3 on the membrane without mineral oxides, NO, NO2, HONO, and NH3 decreased by 17.1, 6.0, 12.6, and 57.1% due to the presence of SO2, respectively. In the photolysis of NH4NO3 on the surface of mineral oxides, SO2 also exhibited an inhibitory effect on the production of NOx, HONO, and NH3 due to its reducibility and acidic products, while the increase in surface acidity due to the accumulation of abundant sulfate on TiO2 and MgO promoted the release of HONO. On the photoactive oxide TiO2, HSO3-, generated by the uptake of SO2, could compete for holes with nitrate to block nitrate photolysis. This study highlights the interaction between the heterogeneous oxidation of SO2 and nitrate photolysis and provides a new perspective on how SO2 affects the photolysis of nitrate absorbed on the photoactive oxides.

The theoretical design of manganese catalysts with a Si-N-Si-C-Si-C six-membered ring core-based bowl-shaped quadridentate ligand for the hydrogenation of CO/CN bonds.

Herein, a new series of bowl-shaped quadridentate ligands with a Si-N-Si-C-Si-C six-membered ring core and their manganese catalysts were designed using the density functional theory (DFT) method for the hydrogenation of unsaturated CX (XN, O) bonds. The frameworks of these ligands named by LYG (LYG = P(R1)2CH2Si(CH2)(CH3)NSi(CH3)(CH2Si(CH3)CH2P(R3)2)CH2P(R2)2) have a Si-N-Si-C-Si-C six-membered ring core at the bottom of the bowl structure and each Si atom links with one phosphorus arm (-CH2PR2). The Mn catalyst Mn(CO)-LYG was constructed to catalyze the hydrogenation of CO/CN bonds. The calculated results indicate that due to the bowl-shaped structure of LYG quadridentate ligands, these Mn catalysts could be advantageous not only in the tuneup of catalytic activity and stereoselectivity by modifying three phosphorus arms but also in the homogeneous catalyst immobilization by linking with the Si-N-Si-C-Si-C six-membered ring core using different supports. This work might provide theoretical insights to design new framework transition-metal catalysts for the hydrogenation of CX bonds.

Plant Secondary Compounds Promote White Adipose Tissue Browning via Modulation of the Gut Microbiota in Small Mammals.

The browning of white adipose tissue (WAT) is a promising area of research for treating metabolic disorders and obesity in the future. However, studies on plant secondary compounds promoting WAT browning are limited. Herein, we explored the effects of swainsonine (SW) on gut microbiota and WAT browning in captive pikas. SW inhibited body mass gain, increased brown adipose tissue (BAT) mass, and induced WAT browning in pikas. The 16S rDNA sequencing revealed a significant reduction in the alpha diversity and altered community structure of the gut microbiota in captive pikas. However, the addition of SW to the diet significantly increased the alpha diversity of gut microbiota and the relative abundance of Akkermansia, Prevotella, and unclassified_f__Lachnospiraceae, along with the complexity of the microbial co-occurrence network structure, which decreased in the guts of captive pikas. Functional profiles showed that SW significantly decreased the relative abundances of energy metabolism, lipid metabolism, and glycan biosynthesis and metabolism, which were enriched in captive pikas. Furthermore, SW decreased deterministic processes of gut microbiota assembly in July and increased them in November. Finally, the genera Prevotella and unclassified_f__Prevotellaceae were positively correlated with BAT mass. Our results highlighted that plant secondary compounds promote WAT browning by modulating the gut microbiota in small mammals.

Overview of 1,5-Selective Click Reaction of Azides with Alkynes or Their Synthetic Equivalents.

Nowadays, the click reaction of azides with alkynes has evolved rapidly and become one of the most efficient methods to synthesize 1,2,3-triazoles, which are an important class of N-containing heterocycles. While the 1,4-selective click reaction of azides with alkynes is well established to synthesize 1,4-substituted 1,2,3-triazoles, the corresponding 1,5-selective click reaction for the generation of 1,5-substituted-1,2,3-triazoles is much less explored, and there is no systematic review for the 1,5-selective click reaction. This timely review summarizes the discovery and development of 1,5-selective click reactions of azides with alkynes for the synthesis of 1,5-substituted 1,2,3-triazoles. The 1,5-selective click reactions will be divided into three types according to the critical reactive intermediates: metallacyclic intermediates, acetylide intermediate, and formal 1,5-selective azide-alkyne cycloaddition. The related mechanistic studies will also be involved in this review.

Precise Modulation of Intramolecular Aggregation-induced Electrochemiluminescence by Tetraphenylethylene-based Supramolecular Architectures.

The precisely modulated synthesis of programmable light-emitting materials remains a challenge. To address this challenge, we construct four tetraphenylethylene-based supramolecular architectures (SA, SB, SC, and SD), revealing that they exhibit higher electrochemiluminescence (ECL) intensities and efficiencies than the tetraphenylethylene monomer and can be classified as highly efficient and precisely modulated intramolecular aggregation-induced electrochemiluminescence (PI-AIECL) systems. The best-performing system (SD) shows a high ECL cathodic efficiency exceeding that of the benchmark tris(2,2'-bipyridyl)ruthenium(II) chloride in aqueous solution by nearly six-fold. The electrochemical characterization of these architectures in an organic solvent provides deeper mechanistic insights, revealing that SD features the lowest electrochemical band gap. Density functional theory calculations indicate that the band gap of the guest ligand in the SD structure is the smallest and most closely matched to that of the host scaffold. Finally, the SD system is used to realize ECL-based cysteine detection (detection limit=14.4 nM) in real samples. Thus, this study not only provides a precisely modulated supramolecular strategy allowing chromophores to be controllably regulated on a molecular scale, but also inspires the programmable synthesis of high-performance aggregation-induced electrochemiluminescence emitters.

Rigid Enhanced Electrochemiluminescence of 1,2,3-Triaryl Indenes as an Ultrasensitive Sensor for D2O in H2O.

The intriguing aggregation-induced emission has recently been applied in the electrochemiluminescence, called aggregation-induced electrochemiluminescence (AIE-ECL), which is conducive to solving the water insolubility and aggregation-caused quenching for most organic luminescence probes. However, AIE-ECL still has the problems of low luminous efficiency and limited practical application. In this work, we disclosed the AIE-ECL properties of 1,2,3-triaryl-substituted indenes containing rigid structures. Experimental and theoretical investigations demonstrated that such a rigid structure could significantly enhance the aromaticity and stability and thereby the luminescence performance of these indenes. Moreover, according to the finding of hydrogen/deuterium exchange for active hydrogen in indene under electrical excitation, ultrasensitive detection for D2O in H2O was realized by such an indene-based AIE-ECL system. Our research not only provided an attractive strategy to enhance the luminescence property for an AIE-active luminophore but also established a superior sensor toward D2O.

Hydroboration of CO2 to Methyl Boronate Catalyzed by a Manganese Pincer Complex: Insights into the Reaction Mechanism and Ligand Effect.

The conversion of carbon dioxide to fuels, polymers, and chemicals is an attractive strategy for the synthesis of high-value-added products and energy-storage materials. Herein, the density functional theory method was employed to investigate the reaction mechanism of CO2 hydroboration catalyzed by manganese pincer complex, [Mn(Ph2PCH2SiMe2)2NH(CO)2Br]. The carbonyl association and carbonyl dissociation mechanisms were investigated, and the calculated results showed that the carbonyl association mechanism is more favorable with an energetic span of 27.0 kcal/mol. Meanwhile, the solvent effect of the reaction was explored, indicating that the solvents could reduce the catalytic activity of the catalyst, which was consistent with the experimental results. In addition, the X ligand effect (X = CO, Br, H, PH3) on the catalytic activity of the manganese complex was explored, indicating that the anionic complexes [MnI - Br]- and [MnI - H]- have higher catalytic activity. This may not only shed light on the fixation and conversion of CO2 catalyzed by earth-abundant transition-metal complexes but also provide theoretical insights to design new transition-metal catalysts.

A theoretical study of asymmetric ketone hydrogenation catalyzed by Mn complexes: from the catalytic mechanism to the catalyst design.

Herein, a density functional theory (DFT) study was performed to investigate asymmetric ketone hydrogenation (AKH) catalyzed by Mn complexes, from the catalytic mechanism to the catalyst design. The calculated results indicated that the Mn(CO)2-PSiNSiP (A1, PSiNSiP = P(Ph)2Si(CH3)2NSi(CH3)2P(Ph)2) pincer complex has potential high catalytic activity for ketone hydrogenation. The Mn(CO)-LYB (B, LYB = P(Ph)2Si(CH3)2NSi(CH3)2P(Me)2) pincer complex was then designed to catalyze AKH with good stereoselectivity. The hydrogen transfer (HT) step is the chirality-determining step. To avoid the enantiomer of Mn(CO)2-LYB, which could eliminate the high stereoselectivity during AKH, novel Mn complexes with quadridentate ligands, such as Mn(CO)-LYC (C, LYC = P(CH3)2CH2Si(CH3)NSi(CH3)(Si(CH3)CH2P(CH3)2)CH2P(Ph)2) and Mn(CO)-LYD (D, LYD = P(CH3)2CH2Si(CH3)NSi(CH3)(Si(CH3)CH2P(CH3)2)CH2P(Cy)2), were designed to drive AKH with medium stereoselectivity. In order to increase the stereoselectivity of AKH, Mn(CO)-LYE (E, LYE = PH2CH2Si(CH3)NSi(CH3)(Si(CH3)CH2P(CH3)2)CH2P(Ph)2) and Mn(CO)-LYF (F, LYF = PH2CH2Si(CH3)NSi(CH3)(Si(CH3)CH2P(CH3)2)CH2P(Cy)2) were further designed and showed very good stereoselectivity, which is due to the lower deformation energy and stronger interactions between the ketone substrates and catalysts. This work may shed light on the design of cheap metal catalysts with a new ligand framework for the asymmetric hydrogenation (AH) of CX bonds (X = O, N).

Design and Analysis of Area and Energy Efficient Reconfigurable Cryptographic Accelerator for Securing IoT Devices.

Achieving low-cost and high-performance network security communication is necessary for Internet of Things (IoT) devices, including intelligent sensors and mobile robots. Designing hardware accelerators to accelerate multiple computationally intensive cryptographic primitives in various network security protocols is challenging. Different from existing unified reconfigurable cryptographic accelerators with relatively low efficiency and high latency, this paper presents design and analysis of a reconfigurable cryptographic accelerator consisting of a reconfigurable cipher unit and a reconfigurable hash unit to support widely used cryptographic algorithms for IoT Devices, which require block ciphers and hash functions simultaneously. Based on a detailed and comprehensive algorithmic analysis of both the block ciphers and hash functions in terms of basic algorithm structures and common cryptographic operators, the proposed reconfigurable cryptographic accelerator is designed by reusing key register files and operators to build unified data paths. Both the reconfigurable cipher unit and the reconfigurable hash unit contain a unified data path to implement Data Encryption Standard (DES)/Advanced Encryption Standard (AES)/ShangMi 4 (SM4) and Secure Hash Algorithm-1 (SHA-1)/SHA-256/SM3 algorithms, respectively. A reconfigurable S-Box for AES and SM4 is designed based on the composite field Galois field (GF) GF(((22)2)2), which significantly reduces hardware overhead and power consumption compared with the conventional implementation by look-up tables. The experimental results based on 65-nm application-specific integrated circuit (ASIC) implementation show that the achieved energy efficiency and area efficiency of the proposed design is 441 Gbps/W and 37.55 Gbps/mm2, respectively, which is suitable for IoT devices with limited battery and form factor. The result of delay analysis also shows that the number of delay cycles of our design can be reduced by 83% compared with the state-of-the-art design, which shows that the proposed design is more suitable for applications including 5G/Wi-Fi/ZigBee/Ethernet network standards to accelerate block ciphers and hash functions simultaneously.

Aquatic food animals in the United States: Status quo and challenges.

This review summarizes (1) the U.S. status quo for aquatic food animal production and marketing; (2) major food safety and quality issues/concerns for aquatic food animals in the United States, including fish misbranding, finfish/shellfish allergies, pathogens, toxins and harmful residues, microplastics, and genetically engineered salmon; and (3) various U.S. regulations, guidances, and detection methods for the surveillance of fishery products. Overall, fish misbranding is the biggest challenge in the United States due to the relatively low inspection rate. In addition, due to the regulatory differences among countries, illegal animal drugs and/or pesticide residues might also be identified in imported aquatic food animals. Future regulatory and research directions could focus on further strengthening international cooperation, enhancing aquatic food animal inspection, and developing reliable, sensitive, and highly efficient detection methods.