Flat-band Friedrich-Wintgen bound states in the continuum based on borophene metamaterials.

Many applications involve the phenomenon of a material absorbing electromagnetic radiation. By exploiting wave interference, the efficiency of absorption can be significantly enhanced. Here, we propose Friedrich-Wintgen bound states in the continuum (F-W BICs) based on borophene metamaterials to realize coherent perfect absorption with a dual-band absorption peak in commercially important communication bands. Metamaterials consist of borophene gratings and a borophene sheet that can simultaneously support a Fabry-Perot plasmon resonance and a guided plasmon mode. The formation and dynamic modulation of the F-W BIC can be achieved by adjusting the width or carrier density of the borophene grating, while the strong coupling leads to the anti-crossover behavior of the absorption spectrum. Due to the weak angular dispersion originating from the intrinsic flat-band characteristic of the deep sub-wavelength periodic structure, the proposed plasmonic system exhibits almost no change in wavelength and absorption at large incident angles (within 70 degrees). In addition, we employ the temporal coupled-mode theory including near- and far-field coupling to obtain strong critical coupling, successfully achieve coherent perfect absorption, and can realize the absorption switch by changing the phase difference between the two coherent beams. Our findings can offer theoretical support for absorber design and all-optical tuning.

A Survey on Information Bottleneck.

This survey is for the remembrance of one of the creators of the information bottleneck theory, Prof. Naftali Tishby, passing away at the age of 68 on August, 2021. Information bottleneck (IB), a novel information theoretic approach for pattern analysis and representation learning, has gained widespread popularity since its birth in 1999. It provides an elegant balance between data compression and information preservation, and improves its prediction or representation ability accordingly. This survey summarizes both the theoretical progress and practical applications on IB over the past 20-plus years, where its basic theory, optimization, extensive models and task-oriented algorithms are systematically explored. Existing IB methods are roughly divided into two parts: traditional and deep IB, where the former contains the IBs optimized by traditional machine learning analysis techniques without involving any neural networks, and the latter includes the IBs involving the interpretation, optimization and improvement of deep neural works (DNNs). Specifically, based on the technique taxonomy, traditional IBs are further classified into three categories: Basic, Informative and Propagating IB; While the deep IBs, based on the taxonomy of problem settings, contain Debate: Understanding DNNs with IB, Optimizing DNNs Using IB, and DNN-based IB methods. Furthermore, some potential issues deserving future research are discussed. This survey attempts to draw a more complete picture of IB, from which the subsequent studies can benefit.

Multitask Image Clustering via Deep Information Bottleneck.

Multitask image clustering approaches intend to improve the model accuracy on each task by exploring the relationships of multiple related image clustering tasks. However, most existing multitask clustering (MTC) approaches isolate the representation abstraction from the downstream clustering procedure, which makes the MTC models unable to perform unified optimization. In addition, the existing MTC relies on exploring the relevant information of multiple related tasks to discover their latent correlations while ignoring the irrelevant information between partially related tasks, which may also degrade the clustering performance. To tackle these issues, a multitask image clustering method named deep multitask information bottleneck (DMTIB) is devised, which aims at conducting multiple related image clustering by maximizing the relevant information of multiple tasks while minimizing the irrelevant information among them. Specifically, DMTIB consists of a main-net and multiple subnets to characterize the relationships across tasks and the correlations hidden in a single clustering task. Then, an information maximin discriminator is devised to maximize the mutual information (MI) measurement of positive samples and minimize the MI of negative ones, in which the positive and negative sample pairs are constructed by a high-confidence pseudo-graph. Finally, a unified loss function is devised for the optimization of task relatedness discovery and MTC simultaneously. Empirical comparisons on several benchmark datasets, NUS-WIDE, Pascal VOC, Caltech-256, CIFAR-100, and COCO, show that our DMTIB approach outperforms more than 20 single-task clustering and MTC approaches.

Cross-Modal Clustering With Deep Correlated Information Bottleneck Method.

Cross-modal clustering (CMC) intends to improve the clustering accuracy (ACC) by exploiting the correlations across modalities. Although recent research has made impressive advances, it remains a challenge to sufficiently capture the correlations across modalities due to the high-dimensional nonlinear characteristics of individual modalities and the conflicts in heterogeneous modalities. In addition, the meaningless modality-private information in each modality might become dominant in the process of correlation mining, which also interferes with the clustering performance. To tackle these challenges, we devise a novel deep correlated information bottleneck (DCIB) method, which aims at exploring the correlation information between multiple modalities while eliminating the modality-private information in each modality in an end-to-end manner. Specifically, DCIB treats the CMC task as a two-stage data compression procedure, in which the modality-private information in each modality is eliminated under the guidance of the shared representation of multiple modalities. Meanwhile, the correlations between multiple modalities are preserved from the aspects of feature distributions and clustering assignments simultaneously. Finally, the objective of DCIB is formulated as an objective function based on a mutual information measurement, in which a variational optimization approach is proposed to ensure its convergence. Experimental results on four cross-modal datasets validate the superiority of the DCIB. Code is released at https://github.com/Xiaoqiang-Yan/DCIB.

Multiview Clustering With Propagating Information Bottleneck.

In many practical applications, massive data are observed from multiple sources, each of which contains multiple cohesive views, called hierarchical multiview (HMV) data, such as image-text objects with different types of visual and textual features. Naturally, the inclusion of source and view relationships offers a comprehensive view of the input HMV data and achieves an informative and correct clustering result. However, most existing multiview clustering (MVC) methods can only process single-source data with multiple views or multisource data with single type of feature, failing to consider all the views across multiple sources. Observing the rich closely related multivariate (i.e., source and view) information and the potential dynamic information flow interacting among them, in this article, a general hierarchical information propagation model is first built to address the above challenging problem. It describes the process from optimal feature subspace learning (OFSL) of each source to final clustering structure learning (CSL). Then, a novel self-guided method named propagating information bottleneck (PIB) is proposed to realize the model. It works in a circulating propagation fashion, so that the resulting clustering structure obtained from the last iteration can "self-guide" the OFSL of each source, and the learned subspaces are in turn used to conduct the subsequent CSL. We theoretically analyze the relationship between the cluster structures learned in the CSL phase and the preservation of relevant information propagated from the OFSL phase. Finally, a two-step alternating optimization method is carefully designed for optimization. Experimental results on various datasets show the superiority of the proposed PIB method over several state-of-the-art methods.

A phase 2 study of interleukin-22 and systemic corticosteroids as initial treatment for acute GVHD of the lower GI tract.

Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality following allogeneic hematopoietic transplantation. In experimental models, interleukin-22 promotes epithelial regeneration and induces innate antimicrobial molecules. We conducted a multicenter single-arm phase 2 study evaluating the safety and efficacy of a novel recombinant human interleukin-22 dimer, F-652, used in combination with systemic corticosteroids for treatment of newly diagnosed lower gastrointestinal acute GVHD. The most common adverse events were cytopenias and electrolyte abnormalities, and there were no dose-limiting toxicities. Out of 27 patients, 19 (70%; 80% confidence interval, 56%-79%) achieved a day-28 treatment response, meeting the prespecified primary endpoint. Responders exhibited a distinct fecal microbiota composition characterized by expansion of commensal anaerobes, which correlated with increased overall microbial α-diversity, suggesting improvement of GVHD-associated dysbiosis. This work demonstrates a potential approach for combining immunosuppression with tissue-supportive strategies to enhance recovery of damaged mucosa and promote microbial health in patients with gastrointestinal GVHD. This trial was registered at www.clinicaltrials.gov as NCT02406651.

A comprehensive multi-omics analysis reveals molecular features associated with cancer via RNA cross-talks in the Notch signaling pathway.

The Notch signaling has an important role in multiple cellular processes and is related to carcinogenic process. To understand the potential molecular features of the crucial Notch pathway, a comprehensive multi-omics analysis is performed to explore its contributions in cancer, mainly including analysis of somatic mutation landscape, pan-cancer expression, ncRNA regulation and potential prognostic power. The screened 22 Notch core genes are relative stable in DNA variation. Dynamic expression patterns are associated with the Notch activity, which are mainly regulated by multiple ncRNAs via interactions of ncRNA:mRNA and ceRNA networks. The Notch pathway shows a potential prognostic ability through integrating multi-omics features as well as their targets, and it is correlated with immune infiltration and maybe available drug targets, implying the potential role in individualized treatment. Collectively, all of these findings contribute to exploring crucial role of the key pathway in cancer pathophysiology and gaining mechanistic insights into cross-talks among RNAs and biological pathways, which indicates the possible application of the well-conserved Notch signaling pathway in precision medicine.

A comprehensive analysis of ncRNA-mediated interactions reveals potential prognostic biomarkers in prostate adenocarcinoma.

As one of common malignancies, prostate adenocarcinoma (PRAD) has been a growing health problem and a leading cause of cancer-related death. To obtain expression and functional relevant RNAs, we firstly screened candidate hub mRNAs and characterized their associations with cancer. Eight deregulated genes were identified and used to build a risk model (AUC was 0.972 at 10 years) that may be a specific biomarker for cancer prognosis. Then, relevant miRNAs and lncRNAs were screened, and the constructed primarily interaction networks showed the potential cross-talks among diverse RNAs. IsomiR landscapes were surveyed to understand the detailed isomiRs in relevant homologous miRNA loci, which largely enriched RNA interaction network due to diversities of sequence and expression. We finally characterized TK1, miR-222-3p and SNHG3 as crucial RNAs, and the abnormal expression patterns of them were correlated with poor survival outcomes. TK1 was found synthetic lethal interactions with other genes, implicating potential therapeutic target in precision medicine. LncRNA SNHG3 can sponge miR-222-3p to perturb RNA regulatory network and TK1 expression. These results demonstrate that TK1:miR-222-3p:SNHG3 axis may be a potential prognostic biomarker, which will contribute to further understanding cancer pathophysiology and providing potential therapeutic targets in precision medicine.

A Class of Readily Tunable Planar-Chiral Cyclopentadienyl Rhodium(III) Catalysts for Asymmetric C-H Activation.

Chiral half-sandwich cyclopentadienyl rhodium(III) (CpRhIII ) complexes are powerful catalysts for promoting asymmetric C-H activation reactions. Their preparation normally involved linking or embedding the Cp motif to or into a certain chiral backbone to forge the so-called chiral Cp ligand. However, preparation of a planar-chiral CpRhIII catalyst bearing a non-chiral Cp ligand remains a formidable challenge and is rarely reported. We describe herein an unusual class of planar-chiral rhodium catalysts bearing non-chiral Cp ligands. Different from existing ones, this catalyst is readily tunable. Ten planar-chiral only CpRhIII catalysts were prepared with ease, and successfully used in two enantioselective C-H activation reactions. Given its convenient synthesis and high structural tunability, these catalysts are expected to find more utilities in asymmetric C-H activation.

Preclinical characterization and comparison between CD3/CD19 bispecific and novel CD3/CD19/CD20 trispecific antibodies against B-cell acute lymphoblastic leukemia: targeted immunotherapy for acute lymphoblastic leukemia.

The CD19-targeting bispecific T-cell engager blinatumomab has shown remarkable efficacy in patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia. However, several studies showed that blinatumomab has a short plasma half-life due to its low molecular weight, and thus its clinical use is limited. Furthermore, multiple trials have shown that approximately 30% of blinatumomab-relapsed cases are characterized by CD19 negative leukemic cells. Here, we design and characterize two novel antibodies, A-319 and A-2019. Blinatumomab and A-319 are CD3/CD19 bispecific antibodies with different molecular sizes and structures, and A-2019 is a novel CD3/CD19/CD20 trispecific antibody with an additional anti-CD20 function. Our in vitro, ex vivo, and in vivo experiments demonstrated that A-319 and A-2019 are potent antitumor agents and capable of recruiting CD3 positive T cells, enhancing T-cell function, mediating B-cell depletion, and eventually inhibiting tumor growth in Raji xenograft models. The two molecules are complementary in terms of efficacy and specificity profile. The activity of A-319 demonstrated superior to that of A-2019, whereas A-2019 has an additional capability to target CD20 in cells missing CD19, suggesting its potential function against CD19 weak or negative CD20 positive leukemic cells.

5G Edge Computing Enabled Directional Data Collection for Medical Community Electronic Health Records.

It is important to promote the development and application of hospital information system, community health service system, etc. However, it is difficult to realize the intercommunication between various information systems because it is not enough to realize the in-depth management of health information. To address these issues, we design the 5G edge computing-assisted architecture for medical community. Then, we formulate the directional data collection (DDC) problem to gather the EMR/HER data from the medical community to minimize the service error under the deadline constraint of data collection deadline. Moreover, we design the data direction prediction algorithm (DDPA) to predict the data collection direction and propose the data collection planning algorithm (DCPA) to minimize the data collecting time cost. Through the numerical simulation experiments, we demonstrate that our proposed algorithms can decrease the total time cost by 62.48% and improve the data quality by 36.47% through the designed system, respectively.

A label-free electrochemical biosensor based on magnetic biocomposites with DNAzyme and hybridization chain reaction dual signal amplification for the determination of Pb2.

A highly sensitive and selective electrochemical biosensor for Pb2+ with a dual-amplification strategy is proposed. The first amplification step was realized by the cycle of Pb2+ and 8-17 DNAzyme (S2), and the hybridization chain reaction (HCR) triggered by S1 further amplified the electrochemical signal. Fe3O4@Au NPs, as a multifunctional magnetic carrier, is not only manifested in the construction of a magnetically controlled electrochemical response interface, but also has significant contribution in the purifying system, reducing interference, increasing the specific surface area, and the DNA loading. The magnetic nanocomposites were characterized by TEM as spheres with particle size of around 39 nm. When there was no Pb2+, long double-strand DNA (dsDNA) is formed on the surface of Fe3O4@Au NPs by the S1-triggered HCR; in the presence of Pb2+, S2 is activated and S1 on the surface of magnetic biocomposites (Fe3O4@Au NPs-S1) is continuously cleaved with the cycle of Pb2+ and S2, leading to a significant decrease of methylene blue (MB) absorbed on dsDNA. Such reverse dual-signal amplification strategy effectively increased the current difference and improved the sensitivity of the proposed sensor. The electrochemical signal of MB was obtained by differential pulse voltammetry (DPV) with preconcentration, showing a linear response toward Pb2+ ranging from 50 pM to 1 µM with a detection limit of 15 pM. The proposed method has feasible applications in detecting other heavy metal ions based on other metal-dependent DNAzyme. Graphical Abstract.

A label-free electrochemical magnetic aptasensor based on exonuclease III-assisted signal amplification for determination of carcinoembryonic antigen.

A novel label-free and exonuclease III (Exo III)-assisted signal amplification electrochemical aptasensor was constructed for the determination of carcinoembryonic antigen (CEA) via magnetic field-induced self-assembly of magnetic biocomposites (Fe3O4@Au NPs-S1-S2-S3). The magnetic biocomposites were acquired by modifying double-stranded DNA (S1-S2-S3) on the surface of Fe3O4@Au nanoparticles (Fe3O4@Au NPs). Among them, Fe3O4@Au NPs were used as carriers for magnetic separation, thiolated single-stranded DNA (S1) provided signal sequence, CEA aptamer (S2) worked as a recognition element, and complementary strand (S3) was used to form double strands. In the presence of CEA, S2 bonded with CEA competitively; the exposed S1 could not be cleaved since Exo III was inactive against ssDNA. The G-quadruplex/hemin complexes finally formed with the existence of K+, and the high electrochemical signal of G-quadruplex/hemin complexes was recorded by differential pulse voltammetry (DPV) at - 0.6 V. Conversely, in the absence of CEA, dsDNA was cleaved from the 3' blunt end by Exo III; the disappearance of G-rich sequence blocked the generation of the signal. This method exhibited good selectivity and sensitivity for the determination of CEA; the linear range was from 0.1 to 200 ng mL-1 and the limit of detection was 0.4 pg mL-1. Graphical abstract.

Chiral Bicyclo[2.2.2]octane-Fused CpRh Complexes: Synthesis and Potential Use in Asymmetric C-H Activation.

A new class of chiral cyclopentadienyl rhodium(I) complexes (CpRhI ) bearing C2 -symmetric chiral bridged-ring-fused Cp ligands was prepared. The complexes were successfully applied to the asymmetric C-H activation reaction of N-methoxybenzamides with quinones, affording a series of chiral hydrophenanthridinones in up to 82 % yield with up to 99 % ee. Interestingly, structure analysis reveals that the side wall of the optimal chiral CpRhI catalyst is vertically more extended, horizontally less extended, and closer to the metal center in comparison with the classic binaphthyl and spirobiindanyl CpRhI complexes, and may thus account for its superior catalytic performance.

A signal transduction approach for multiplexed detection of transcription factors by integrating DNA nanotechnology, multi-channeled isothermal amplification, and chromatography.

The variation patterns of transcription factors (TFs) provide direct information for the states of cell populations, which is of significance for biomedical research and clinical diagnostics. Herein, we show that through multi-channeled isothermal amplification, it is feasible to connect DNA-based signal transduction with chromatography for multiplexed detection of TFs. The described system is referred to as "PAC" which includes three major steps: (i) Protection, which uses DNA-modified magnetic beads to capture TFs and converts the capturing event into triggering signal; (ii) Amplification, which receives the triggering signal and generate DNA reporters through multi-channeled extension and nicking of oligonucleotides; and (iii) Chromatography, which separates and detects the DNA reporters in liquid chromatography. The quantitative detection of five essential TFs includes p50, p53, AP-1, MITF, and c-Myc is realized in a multiplexed manner, with the lowest detection limit of 0.5 pM. PAC can also provide effective means to measure the above five TFs in real samples, including cultured cells, xenograft tumors, and blood-based liquid biopsy. This study not only established a solution for multiplexed measurement of TFs for molecular diagnostics, but also paved avenue for bridging the gap between DNA nanotechnology and chromatography.

Dual-Emission Reverse Change Ratio Photoluminescence Sensor Based on a Probe of Nitrogen-Doped Ti3C2 Quantum Dots@DAP to Detect H2O2 and Xanthine.

Titanium carbide quantum dots (Ti3C2 QDs) derived from two-dimensional (2D) Ti3C2Tx (MXene) are the rising-star material recently. Herein, nitrogen-doped Ti3C2 QDs (N-Ti3C2 QDs) were synthesized via a solvothermal method. The obtained N-Ti3C2 QDs exhibited excitation-dependent photoluminescence, antiphotobleaching, and dispersion stability. Furthermore, by combining the N-Ti3C2 QDs and DAP (2,3-diaminophenazine, the oxidative product of o-phenylenediamine) as a composite nanoprobe (N-Ti3C2 QDs@DAP), we developed a dual-emission reverse change ratiometric sensor to quantitatively monitor H2O2 based on photoinduced electron-transfer effects, where N-Ti3C2 QDs acted as the donor and DAP as the acceptor. On the basis of the xanthine converting into H2O2 through the catalysis of xanthine oxidase, the N-Ti3C2 QDs@DAP nanoprobe was also exploited for xanthine sensing. As a result, the proposed assay was demonstrated to be highly sensitive for H2O2 and xanthine with detection limits of 0.57 and 0.34 µM, respectively. In a word, we have investigated the application of N-Ti3C2 QDs in H2O2 and xanthine sensing and opened a new and exciting avenue for the N-Ti3C2 QDs in biosensing.

Rhodium(III)-Catalyzed Asymmetric C-H Activation of N-Methoxybenzamide with Quinone and Its Application in the Asymmetric Synthesis of a Dihydrolycoricidine Analogue.

A chiral CpRhIII-catalyzed asymmetric C-H activation reaction of N-methoxybenzamides with quinones has been developed to efficiently forge chiral tricyclic hydrophenanthridinone scaffolds in ≤88% yield and ≤94% ee. With this methodology as the key step, an enantioenriched dihydrolycoricidine derivative has been synthesized in 64% overall yield in five steps.

An electrochemical and fluorescence dual-signal assay based on Fe3O4@MnO2 and N-doped carbon dots for determination of hydrogen peroxide.

A novel electrochemical and fluorescence dual-signal assay was developed for the determination of hydrogen peroxide (H2O2) based on Fe3O4@MnO2 and N-doped carbon dots (NCDs). Fe3O4@MnO2 was not only applied as the recognizer for H2O2 but also served as the fluorescence quencher and electrochemical enhancer. This permits the dual-signal readout of the analytical system. In the absence of H2O2, the NCDs were quenched by Fe3O4@MnO2, and the oxidation of the electrochemical probe ferrocene (Fc) was catalyzed by Fe3O4@MnO2. In the presence of H2O2, MnO2 was reduced to Mn2+, leading to the fluorescence recovery of NCDs and the reduction in the oxidation signal of Fc. By combining the electrochemical method and the fluorescence assay, more comprehensive and valuable information for H2O2 determination was provided to meet different analytical demands. The method exhibits good repeatability and selectivity with a detection limit of 1.0 µM for the fluorescence assay and 0.6 µM for the electrochemical method. The proposed approach holds great potential for probing released targets from living cells. Graphical abstract.

Label-Free Colorimetric Detection of Acid Phosphatase and Screening of Its Inhibitors Based on Biomimetic Oxidase Activity of MnO2 Nanosheets.

In this research, we attempted to develop a sensitive colorimetric sensing strategy for the detection of acid phosphatase (ACP) based on MnO2 nanosheets and explored its applications in screening and evaluating inhibitors of ACP. The MnO2 nanosheets exhibit intrinsic biomimetic oxidase activity, which can catalyze the oxidation of the colorless 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonate) diammonium salt (ABTS) into green oxidized ABTS (oxABTS). Upon the introduction of ACP, l-ascorbic acid-2-phosphate can be dephosphorylated to ascorbic acid, which arouses the disintegration of MnO2 nanosheets into Mn2+ ions. This disintegration weakens the enzyme mimicking activity of the MnO2 nanosheets, leading to the impediment of the oxidation of ABTS. Conversely, in the absence of ACP, the ABTS is rapidly oxidized by MnO2, leading to a significant colorimetric signal change. The absorbance difference at 420 nm displayed a linear relationship with the concentration of ACP ranging from 0.075 to 0.45 mU·mL-1, generating a detection limit of 0.046 mU·mL-1. In the inhibition assays, this sensing platform provided simple detection for parathion-methyl (PM), a representative inhibitor of ACP. The facile evaluation of the inhibitory effect of PM, including its IC50 toward ACP, was also realized.

An Open-Label, Dose-Escalation Study to Assess the Safety and Efficacy of IL-22 Agonist F-652 in Patients With Alcohol-associated Hepatitis.

BACKGROUND AND AIMS: Interleukin-22 has beneficial effects on inflammation and impaired hepatic regeneration that characterize alcohol-associated hepatitis (AH). F-652 is a recombinant fusion protein of human interleukin-22 and immunoglobulin G2 fragment crystallizable. This study aims to assess the safety and efficacy signals of F-652 in patients with moderate and severe AH. APPROACH AND RESULTS: A phase-2 dose-escalating study was carried out. F-652 (10 µg/kg, 30 µg/kg, or 45 µg/kg) administered on days 1 and 7 was tested in 3 patients each with moderate (Model for End-Stage Liver Disease [MELD] scores: 11-20) and severe AH (MELD scores: 21-28). Safety was defined by absence of serious adverse events and efficacy was assessed by Lille score, changes in MELD score, and serum bilirubin and aminotransferases at days 28 and 42. Three independent propensity-matched comparator patient cohorts were used. Plasma extracellular vesicles and multiplex serum cytokines were measured to assess inflammation and hepatic regeneration. Eighteen patients (9 moderate and 9 severe AH) were enrolled, 66% were male, and the mean age was 48 years. The half-life of F-652 following the first dose was 61-85 hours. There were no serious adverse events leading to discontinuation. The MELD score and serum aminotransferases decreased significantly at days 28 and 42 from baseline (P < 0.05). Day-7 Lille score was 0.45 or less in 83% patients as compared with 6%, 12%, and 56% among the comparator cohorts. Extracellular vesicle counts decreased significantly at day 28 (P < 0.013). Cytokine inflammatory markers were down-regulated, and regeneration markers were up-regulated at days 28 and 42. CONCLUSIONS: F-652 is safe in doses up to 45 µg/kg and associated with a high rate of improvement as determined by Lille and MELD scores, reductions in markers of inflammation and increases in markers of hepatic regeneration. This study supports the need for randomized placebo-controlled trials to test the efficacy of F-652 in AH.