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We prove the global space-time bound for the defocusing mass critical nonlinear Schrödinger equation on R 3 perturbed by a small multiplicative noise. The associated scattering behavior is also obtained. In addition to techniques from Fan and Xu (Global well-posedness for the defocusing mass-critical stochastic nonlinear Schrödinger equation on R at L 2 regularity, 2018) and Fan and Zhao (On long time behavior for stochastic nonlinear Schrödinger equations with a multiplicative noise, 2020), the main new ingredients are the decomposition of the solution tailored for the bootstrap argument in this problem, and the incorporation of local smoothing norms to close the argument. We also prove the global space-time Strichartz estimate for the linear stochastic equation. It is a toy model of our nonlinear problem, but the bound itself is new and of its own interest. Furthermore, the proof we give for the linear model is more direct, and also illustrates the proof strategy for the nonlinear problem. [ABSTRACT FROM AUTHOR]

Coronavirus 2019 (COVID‐19) has caused violent fluctuation in stock markets, and led to heated discussion in stock forums. The rise and fall of any specific stock is influenced by many other stocks and emotions expressed in forum discussions. Considering the transmission effect of emotions, we propose a new Textual Multiple Auto Regressive Moving Average (TM‐ARMA) model to study the impact of COVID‐19 on the Chinese stock market. The TM‐ARMA model contains a new cross‐textual term and a new cross‐auto regressive (AR) term that measure the cross impacts of textual emotions and price fluctuations, respectively, and the adjacent matrix which measures the relationships among stocks is updated dynamically. We compute the textual sentiment scores by an emotion dictionary‐based method, and estimate the parameter matrices by a maximum likelihood method. Our dataset includes the textual posts from the Eastmoney Stock Forum and the price data for the constituent stocks of the FTSE China A50 Index. We conduct a sliding‐window online forecast approach to simulate the real‐trading situations. The results show that TM‐ARMA performs very well even after the attack of COVID‐19. [ABSTRACT FROM AUTHOR]

[Display omitted] Hydrogel-based drug delivery holds great promise in topical tumor treatment. However, the simple construction of multifunctional therapeutic hydrogels under physiological conditions is still a huge challenge. Herein, for the first time, a multifunctional hyaluronan/MnO 2 nanocomposite (HHM) hydrogel with injectable and self-healing capabilities was constructed under physiological conditions through innovative in situ mineralization-triggered Mn-hydrazide coordination crosslinking. The hydrogel formed from Mn2+ and hydrazided hyaluronan under optimized conditions exhibited a high elastic modulus >1 kPa, injectability, self-healing function, stimuli-responsiveness and catalase-like activity. In vitro and in vivo biological experiments demonstrated that our HHM hydrogel could not only efficiently relieve hypoxia by in situ catalytic decomposition of endogenous H 2 O 2 into O 2 but also achieve synergistic photodynamic/photothermal therapy of 4T1 breast cancer in a mouse tumor model. This study presented a novel mineralization-driven metal-hydrazide coordination crosslinking approach and developed a multifunctional therapeutic platform for O 2 -enhanced efficient topical dual-phototherapy of breast cancer. [ABSTRACT FROM AUTHOR]

[Display omitted] Hydrogel-based drug delivery holds great promise in topical tumor treatment. However, the simple construction of multifunctional therapeutic hydrogels under physiological conditions is still a huge challenge. Herein, for the first time, a multifunctional hyaluronan/MnO 2 nanocomposite (HHM) hydrogel with injectable and self-healing capabilities was constructed under physiological conditions through innovative in situ mineralization-triggered Mn-hydrazide coordination crosslinking. The hydrogel formed from Mn2+ and hydrazided hyaluronan under optimized conditions exhibited a high elastic modulus >1 kPa, injectability, self-healing function, stimuli-responsiveness and catalase-like activity. In vitro and in vivo biological experiments demonstrated that our HHM hydrogel could not only efficiently relieve hypoxia by in situ catalytic decomposition of endogenous H 2 O 2 into O 2 but also achieve synergistic photodynamic/photothermal therapy of 4T1 breast cancer in a mouse tumor model. This study presented a novel mineralization-driven metal-hydrazide coordination crosslinking approach and developed a multifunctional therapeutic platform for O 2 -enhanced efficient topical dual-phototherapy of breast cancer. [ABSTRACT FROM AUTHOR]

Cuproptosis is a very newly recognized regulated cell death modality that is distinct from known death mechanisms and shows enormous prospect in cancer treatment. However, its efficacy is copper‐dependent and restricted by strictly regulated copper metabolism. Herein, a novel copper/iron hybrid hollow amorphous metal organic framework (HaMOF) is developed as an oxidative stress amplifier and copper/iron metabolic disrupter for synergistic cuproptosis/ferroptosis/apoptosis anticancer therapy. The HaMOF is fabricated from Cu2+, 3,3′‐dithiobis(propionohydrazide) and Fe3+ via an unsaturated coordination‐etching integration strategy, and then doxorubicin is loaded followed by surface decoration with hyaluronan. The obtained DOX@Fe/CuTH exhibits tumor microenvironment‐triggered catalytic therapeutic property, wherein it can amplify cellular oxidative stress by simultaneously boosting H2O2 production and depleting glutathione. Moreover, it can cause mitochondrial dysfunction and downregulate the expressions of copper transporter ATP7A and iron transporter FPN 1, thereby leading to metabolic disorders and high retentions of copper/iron in cytoplasm for •OH generation. The overloaded Cu2+ can cause lipoylated protein dihydrolipoamide S‐acetyltransferase aggregation and lead to cellular cuproptosis. Collectively, both augmented oxidative stress and overloaded copper/iron induce potent ferroptosis, which synergizes with cuproptosis and DOX‐mediated apoptosis to efficiently suppress tumor growth. This bimetallic hollow nanoplatform provides a new therapeutic modality paradigm to boost cuproptosis‐related therapies. [ABSTRACT FROM AUTHOR]

The reduction of selenite [Se(Ⅳ)] by microorganisms is a green and efficient detoxification strategy. We found that Se(Ⅳ) inhibited exopolysaccharide and protein secretion by Lactiplantibacillus plantarum BSe and compromised cell integrity. In this study, L. plantarum BSe reduced Se(Ⅳ) by increasing related enzyme activity and electron transfer. Genomic analysis demonstrated that L. plantarum BSe should be able to reduce Se(Ⅳ). Further transcriptome analysis showed that L. plantarum BSe enhanced its tolerance to Se(Ⅳ) by upregulating the expression of surface proteins and transporters, thus reducing the extracellular Se(Ⅳ) concentration through related enzymatic reactions and siderophore-mediated pathways. Lactiplantibacillus plantarum BSe was able to regulate the expression of related genes involved in quorum sensing and a two-component system and then select appropriate strategies for Se(Ⅳ) transformation in response to varying environmental Se(Ⅳ) concentrations. In addition, azo reductase was linked to the reduction of Se(Ⅳ) for the first time. The present study established a multipath model for the reduction of Se(Ⅳ) by L. plantarum , providing new insights into the biological reduction of Se(Ⅳ) and the biogeochemical cycle of selenium. [Display omitted] • Se(Ⅳ) compromised cell integrity of L. plantarum BSe and inhibited EPS secretion. • BSe reduces Se(Ⅳ) by improving enzyme activity and electron transfer. • BSe upregulated surface proteins and transporters to resist the Se(Ⅳ) stress. • Azo reductase was found to be related to the reduction of Se(Ⅳ) for the first time. [ABSTRACT FROM AUTHOR]

In group decision making, it is sensible to achive minimum consensus cost (MCC) because the consensus reaching process resources are often limited. In this endeavour, though, there are still two issues that require paying attention to: (1) the impact of decision rules, including decision weights and aggregation functions, on MCC; and (2) the impact of non-cooperative behaviors on MCC. Hence, this paper analytically reveals the decision rules to minimize MCC or maximize MCC. Furthermore, detailed simulation experiments show the joint impact of non-cooperative behavior and decisions rules on MCC, as well as revealing the effect of the consensus within the established MCC target. [ABSTRACT FROM AUTHOR]

Studies have demonstrated that both mortality and severe illness rates exist significant difference in different gender COVID-19 patients, but the reasons are still very mysterious to date. Here, we firstly find that the survival outcome of female patients is better to male patients through analyzing the 3044 COVID-19 cases. Secondly, we identify many important master regulators [e.g. STAT1/STAT2 and zinc finger (ZNF) proteins], in particular female patients can express more ZNF proteins and stronger transcriptional activities than male patients in response to SARS-CoV-2 infection. Thirdly, we discover that ZNF protein activity is significantly negative correlation with the SARS-CoV-2 load of COVID-19 patients, and ZNF proteins as transcription factors can also activate their target genes to participate in anti-SARS-CoV-2 infection. Fourthly, we demonstrate that ZNF protein activity is positive correlation with the abundance of multiple immune cells of COVID-19 patients, implying that the highly ZNF protein activity might promote the abundance and the antiviral activity of multiple immune cells to effectively suppress SARS-CoV-2 infection. Taken together, our study proposes an underlying anti-SARS-COV-2 role of ZNF proteins, and differences in the amount and activity of ZNF proteins might be responsible for the distinct prognosis of different gender COVID-19 patients. [ABSTRACT FROM AUTHOR]

This work includes the design of fully flexible wearable data glove to ensure that strain sensors are accurately connected to the hand joints to accurately measure the joints motions of the finger joints. A real-time flexible wearable gesture-to-alphabets translation system was reported of integrating visual data with somatosensory data from ten flexible stretchable sensors-based data glove and a camera, assisted by machine learning. The device recognized the 26 letters with a recognition rate of up to 99.63% and a recognition time of less than 1 s, which helps to understand observations of sign as words and texts. [Display omitted] • The design of fully flexible wearable data glove. • A system of sign annotation generation to words via integrating visual data with somatosensory data from flexible strain sensor-based data glove is constructed, and the effectiveness of the proposed system is demonstrated through experiments for quantitative evaluations. • A real-time flexible wearable gesture-to-alphabets translation system was reported. • The device recognized the 26 letters with a recognition rate of up to 99.63% and a recognition time of <1 s. Sign language forms a significant way of communication for deaf-mute people. There are different types of sign languages of different countries in different regions. The sign language recognition system translates the gestures into the alphabet, which solves a barrier in comprehension of conversation. Visual techniques and somatosensory strain sensors are both useful modalities to detect sign gesture. In order to improve the recognition accuracy and wear resistance, this paper proposes a real-time alphabets conversion system, which combines the visual data with the data glove based on flexible strain sensor and the somatosensory data of the camera, supplemented by deep learning. In this learning structure, convolutional neural network is used to process the visual data, and then the sparse neural network for sensor data fusion and recognition is realized in the feature layer. A module is proposed to train the linking of hand motions primitives to alphabets (A–Z). The proposed framework is tested on a dataset of sign and descriptive alphabets. The proposed system would recognize the 26 letters with a recognition rate of up to 99.50% and a recognition time of less than 1 s, which helps to understand observations of sign as words and texts. [ABSTRACT FROM AUTHOR]

Prostate cancer gene expression marker 1 (PCGEM1) has been identified as an oncogenic long non-coding RNA (lncRNA) in diverse cancers, but it has never been linked with colorectal cancer (CRC). Former studies have shown the mutual regulation between lncRNAs and transcription factors (TFs) in cancer. CCCTC binding factor (CTCF) has been reported to transcriptionally activate lncRNAs in cancers. We predicted the binding of CTCF on PCGEM1 promoter through UCSC (https://genome.ucsc.edu/), but their relation has not been studied. We aimed to investigate whether and how PCGEM1 functioned in CRC cells and the interaction between PCGEM1 and CTCF. The impacts of PCGEM1 and CTCF inhibition on CRC cells were verified through loss-of-function experiments. Mechanism experiments were used to prove the binding between CTCF and PCGEM1 in CRC progression. PCGEM1 possessed a high expression level in CRC cells as well as tumors. CTCF transcriptionally activated PCGEM1 expression. Knockdown of PCGEM1 or CTCF impeded proliferation and migration and drove apoptosis of CRC cells. Moreover, PCGEM1 bound miR-433–3p to prevent miR-433–3p from targeting CTCF. We first revealed PCGEM1/miR-433–3p/CTCF positive feedback loop as an oncogenic axis in CRC cells, which potentially provides new clues for the advancement of CRC treatment. [ABSTRACT FROM AUTHOR]

• A pioneering "grafting from" drug coordination polymerization strategy was proposed. • A fully-coordinated and full-active Cu 2 O/drug core/shell nanoplatform was prepared. • Obtained nanoplatform-mediated ROS storm could induce immunogenic cell death. • Nanoplatform/αPD-1 combination could induce robust systemic antitumor immunity. Precise manipulation of reactive oxygen species (ROS) breakthrough threshold exhibits great potential in destroying solid tumors, reprogramming "immune-cold" tumor and potentiating immunotherapy. However, it is still challenging to develop efficient ROS initiation devices. Herein, we propose a pioneering "grafting from" drug coordination polymerization strategy and develop a fully-coordinated and full-active Cu 2 O/drug core/shell nanoparticles for multimodal cancer therapy. Chemotherapeutic drug cisplatin (CDDP) and photosensitizer indocyanine green (ICG) were loaded onto the surface of hydrazided hyaluronic acid-decorated Cu 2 O (HA-Cu 2 O) nanoparticles through an infinite hydrazide-cisplatin-sulfonic acid coordination mechanism, obtaining CDDP/ICG-coloaded HA-Cu 2 O (HCCI) nanoplatform. The HCCI nanoplatform exhibited a rapid acid-responsive dissociation behavior and released ICG, Cu+ and CDDP to achieve efficient triple combined photodynamic therapy/chemodynamic therapy/chemotherapy. Importantly, such a combination induced efficient immunogenic cell death cascade mediated by powerful ROS storm to reprogram "immune-cold" tumors and potentiate immunotherapy. The combination of HCCI nanoplatform and αPD-1 not only eradicated primary tumors but effectively inhibited distal tumor growth, lung metastasis and tumor recurrence through reprogramming tumor microenvironment and activating CD8+ T cell antitumor immunity. Collectively, we have presented a drug coordination polymerization loading strategy to develop a robust multimodal antitumor nanoplatform, and this study provides a new direction for the design of nanodrug delivery systems. [ABSTRACT FROM AUTHOR]

A novel and all-active aMOF, DOX@FeTH, is developed via a one-step self-assembly strategy. The aMOF can effectively suppress tumor growth via a ferroptosis-apoptosis synergetic therapeutic modality. Moreover, the aMOF has excellent photothermal performance and the hyperthermia can enhance tumor penetration and further improve antitumor effect. Owing to simple ingredients, facile preparation process, and integrated multifunctionalities, DOX@FeTH aMOF holds great potential for clinical translation. [Display omitted] • A novel aMOF with triple-stimuli responsiveness was prepared via one-pot method. • The aMOF with favorable photothermal effect could penetrate deeply into tumor. • Self-supplied Fe2+, inactivated GPX4 and elevated H 2 O 2 co-induced ferroptosis. • The aMOF killed tumor cells via a ferroptosis-apoptosis synergistic modality. The combination of ferroptosis and apoptosis that act with different mechanisms holds enormous potential in cancer treatment. However, how to simply but effectively integrate the two modalities into a single platform is an enormous challenge. Herein, based on our newly discovered Fe(II)-hydrazide coordination self-assembly strategy, we design and develop an all-active amorphous metal organic framework (aMOF) for photothermally boosted ferroptosis-apoptosis synergistic anti-tumor therapy. The aMOF is prepared via one-pot co-assembly of doxorubicin (DOX), Fe2+ ions and 3,3′-dithiobis(propionohydrazide) (TPH) and subsequent decoration with TPH-functionalized hyaluronic acid. The obtained DOX@FeTH is amorphous in structure, and it exhibits favorable photothermal performance and displays pH/GSH/laser triple-responsive degradation behavior. The aMOF can be specifically internalized by CD44-overexpressed 4T1 cells and efficiently inhibit GPX4 activity via disulfide bond-mediated glutathione depletion, elevate intracellular H 2 O 2 level by DOX-induced NOX4 activation, and consequently amplify lipid peroxidation with the assistance of self-supplied Fe2+, resulting in remarkable ferroptotic cell death. Meanwhile, the released DOX causes apoptotic cell death. Moreover, the aMOF-mediated hyperthermia can promote tumor penetration and augment the synergistic efficacy. Hence, the tumors are effectively suppressed by the synergistic treatment of DOX@FeTH with laser. This work provides a new strategy for fabricating aMOFs and opens a new horizon for tumor treatment. [ABSTRACT FROM AUTHOR]

2D cell culture is widely utilized to develop anti-cancer drugs and to explore the mechanisms of cancer tumorigenesis and development. However, the findings obtained from 2D culture often fail to provide guidance for clinical tumor treatments since it cannot precisely replicate the features of real tumors. 3D tumor models capable of recapitulating native tumor microenvironments have been proved to be a promising alternative technique. Herein, we constructed a breast tumor model from novel hyaluronic acid (HA) hydrogel which was prepared through photocrosslinking of methacrylated HA. The hydrogel was used as a biomimetic extracellular matrix to incubate MCF-7 cells. It was found that methacrylation degree had great effects on hydrogel's microstructure, mechanical performances, and liquid-absorbing and degradation abilities. Optimized hydrogel exhibited highly porous morphology, high equilibrium swelling ratio, suitable mechanical properties, and hyaluronidase-responsive degradation behavior. The results demonstrated that the HA hydrogel facilitated MCF-7 cell proliferation and growth in an aggregation manner. Furthermore, 3D-cultured MCF-7 cells not only up-regulated the expression of VEGF, bFGF and interleukin-8 but exhibited greater invasion and tumorigenesis capabilities compared with 2D-cultured cells. Therefore, the HA hydrogel is a reliable substitute for tumor model construction. [Display omitted] • The hyaluronic acid hydrogel was synthesized by a facile photo-crosslinking approach. • 3D breast tumor models were successfully constructed from hyaluronic acid hydrogels. • 3D-cultured MCF-7 cells efficiently replicated key cellular features of tumor in vivo. • 3D-cultured MCF-7 cells exhibited enhanced tumorigenicity than 2D-cultured ones. [ABSTRACT FROM AUTHOR]

Immunotherapy shows great promise in the treatment of hepatocellular carcinoma (HCC), however, the low response rate of HCC patients to immunotherapy caused by inadequately immunogenic and immunosuppressive tumor microenvironment (TME) is a huge challenge. Herein, a donut‐like multifunctional polysaccharide nanoplatform (GH‐PID) is constructed from doxorubicin/aldehyde hyaluronan nanoring, indocyanine green/hydroxyethyl chitosan nanocomplex, and HCC‐bitargeted galactosamine‐hyaluronan conjugate via a facile self‐assembly process. The GH‐PID nanodonuts exhibit excellent HCC‐targeted ability and synergetic photochemotherapy effect with a coefficient index of about 0.44. Moreover, near infrared laser‐irradiated GH‐PID nanodonuts show robust therapeutic efficacy in HCC mouse models by virtue of photochemotherapy‐augmented immunogenic cell death (ICD) effect. The remarkable ICD in combination with programmed death‐1 antibody efficiently eradicates primary tumors and inhibits distant tumor growth and lung metastasis of HCC by maturing dendritic cells, increasing CD8+ T cell infiltration, suppressing the expansion and trafficking of immunosuppressive myeloid‐derived suppressor cells, and ameliorating immunosuppressive TME. This study provides a facile and versatile strategy to construct polysaccharide nanodonuts integrating multifunctionality and highly efficient HCC‐targeted ability, and the nanodonuts‐based ICD inducer holds great promise for potentiating systemic antitumor immunity and programmed death‐1/programmed death‐ligand 1 blockade efficacy. [ABSTRACT FROM AUTHOR]

Temporal dependency and mutual impact are two major aspects of the qualitative analysis of stock prices. Modeling the dynamic and complex nature of both the timeline and the mutual impact network is a challenging task for stock price prediction. Furthermore, if we want to capture the high-frequency changes of stock price, the time series will become extremely long, leading to a practical challenge in terms of modeling. To address these challenges, this paper proposes a novel memory-based hierarchical recurrent neural encoder (MHieR-encoder) to embed the time series of stock price into a new representation that preserves (i) the sequential dependency of the time series and (ii) the proximity relationships across stocks in the impact network. The hierarchical structure of the proposed model can easily capture the long-range dependence from an extremely long time series, including in terms of high-frequency prices. Moreover, to capture the dynamic mutual impact across stocks, the intermediate results of the impact network will be stored in the memory module to support further exploration at the training stage. The method is validated using an extremely long time series composed of the one-minute prices derived from the all the Chinese stocks. The results show that MHieR-encoder outperforms all the 8 baselines in the bull market, bear market, calm bull market and calm bear market, and significantly improves the accuracy to 52.2% in a three-class prediction: rising, falling and flat. [ABSTRACT FROM AUTHOR]

As an emerging cancer treatment strategy, reactive oxygen species-based tumor catalytic therapies face enormous challenges due to hypoxia and the overexpression of glutathione (GSH) in the tumor microenvironment. Herein, a self-assembled copper-based nanoplatform, TCCHA, was designed for enzyme-like catalysis-enhanced chemodynamic/photodynamic/antiangiogenic tritherapy against hepatocellular carcinoma. TCCHA was fabricated from Cu2+, 3,3′-dithiobis (propionohydrazide), and photosensitizer chlorine e6 via a facile one-pot self-assembly strategy, after which an aldehyde hyaluronic acid was coated, followed by loading of the antivascular drug AL3818. The obtained TCCHA nanoparticles exhibited pH/GSH dual-responsive drug release behaviors and multienzymatic activities, including Fenton, glutathione peroxidase-, and catalase-like activities. TCCHA, a redox homeostasis disruptor, promotes ⋅OH generation and GSH depletion, thus increasing the efficacy of chemodynamic therapy. TCCHA, which has catalase-like activity, can also reinforce the efficacy of photodynamic therapy by amplifying O2 production. In vivo, TCCHA efficiently inhibited tumor angiogenesis and suppressed tumor growth without apparent systemic toxicity. Overall, this study presents a facile strategy for the preparation of multienzyme-like nanoparticles, and TCCHA nanoparticles display great potential for enzyme catalysis-enhanced chemodynamic/photodynamic/antiangiogenic triple therapy against cancer. [ABSTRACT FROM AUTHOR]

[Display omitted] Copper-based nanomaterials show considerable potential in the chemodynamic therapy of cancers. However, their clinical application is restricted by low catalytic activity in tumor microenvironment and copper-induced tumor angiogenesis. Herein, a novel copper-doxorubicin-anlotinib (CDA) nanoconjugate was constructed by the combination of copper-hydrazide coordination, hydrazone linkage and Schiff base bond. The CDA nanoconjugate consists of a copper-3,3′-dithiobis(propionohydrazide)-doxorubicin core and an anlotinib-hyaluronan shell. Benefiting from hyaluronan camouflage and abundant disulfide bonds and Cu2+, the CDA nanoconjugate possessed excellent tumor-targeting and glutathione-depleting abilities and enhanced chemodynamic efficacy. Released doxorubicin significantly improved copper-mediated chemodynamic therapy by upregulating nicotinamide adenine dinucleotide phosphate oxidase 4 expression to increase intracellular H 2 O 2 level. Furthermore, the nanoconjugate produced excessive •OH to induce lipid peroxidation and mitochondrial dysfunction, thus greatly elevating doxorubicin-mediated chemotherapy. Importantly, anlotinib effectively inhibited the angiogenic potential of copper ions. In a word, the CDA nanoconjugate is successfully constructed by combined coordination and pH-responsive linkages, and displays the great potential of copper-drug conjugate for targeted synergistic chemo/chemodynamic/antiangiogenic triple therapy against cancers. [ABSTRACT FROM AUTHOR]

The inertness of carbon felt as cathode is still one of the challenges encountered in the degradation of pollutants by electro-Fenton. In this study, we used a simple ultrasonic oxidation method to introduce oxygen-containing groups and defect carbons on carbon felt surface to improve the electro-Fenton performance. The modified carbon felts were prepared by ultrasonic treatment in three dilute solutions of HNO3, H2SO4, and HNO3–H2SO4. Ultrasound can provide an extra energetic environment to accelerate the oxidation process, while NO3− has stronger oxidation properties in the presence of excess H+, greatly increasing the amounts of C–O–C/C=O and C–C active sites on carbon felt surface. And an electro-Fenton system with modified CF as the cathode was used to degrade rhodamine B, and the factors affecting the degradation were discussed. The results showed that the modified cathode material was significantly more efficient in degrading rhodamine B, under the conditions of O2 flow rate of 0.3 L min−1, pH = 3, voltage of − 0.7 V, and addition of 0.2-mM Fe2+, HNO3–H2SO4 solution modified CF with 37% higher than that of the raw CF, and the decolorization rate reached 96% after 120 min. Modified carbon felt still has good degradation properties after 5 cycles. The CF was modified by ultrasonic oxidation technique to introduce oxygen-containing functional groups and C-sp3 on the surface of the carbon felt.Using this CF as a cathode for the degradation of RhB in an electro-Fenton system. [ABSTRACT FROM AUTHOR]

Background: Acute paraquat poisoning-induced multiple organ dysfunction syndrome (MODS) leads to the high mortality. This study aimed to investigate the clinical significance of microRNA-200b-3p (miR-200b-3p), an upstream inhibitor of high-mobility group box 1 (HMGB1), in acute paraquat poisoning patients for the prediction of MODS and survival. Methods: This study enrolled 80 patients with MODS induced by paraquat and 94 healthy volunteers. The interaction between miR-200b-3p and HMGB1 was identified by luciferase reporter assay. miR-200b-3p levels were measured by quantitative real-time (QRT) PCR. High-mobility group box 1 levels were measured by enzyme-linked immune sorbent assay (ELISA). Receiver operating characteristic analysis was used to evaluate the diagnostic value of miR-200b-3p in screening MODS patients. The relationship between miR-200b-3p and the 28-day survival of MODS patients was evaluated by Kaplan–Meier curves and log-rank test. Cox regression analysis was used to assess the prognostic value of miR-200b-3p. Correlation between miR-200b-3p and HMGB1 was confirmed by Pearson's correlation analysis. Results: miR-200b-3p directly target HMGB1. miR-200b-3p, decreased in MODS patients, had high diagnostic value to screen MODS patients from healthy controls. Additionally, serum miR-200b-3p was decreased in non-survivors, and patients with low miR-200b-3p level had poor 28-day survival. Serum miR-200b-3p could independently predict the survival prognosis. Moreover, serum HMGB1 level was increased in MODS patients, and was negatively correlated with miR-200b-3p level. Conclusion: Decreased miR-200b-3p may function as a biomarker for the diagnosis and survival prognosis of MODS patients, and miR-200b-3p may be involved in the progression of acute paraquat-induced MODS via regulating inflammatory responses by targeting HMGB1. [ABSTRACT FROM AUTHOR]

This study examines the asymmetric volatility spillover effect using realized measures across 22 international stock markets. The findings suggest a high connectedness among global equity markets, with downside risk spillover significantly higher than upside risk spillover over time. Besides, Europe has a higher connectedness than the American and Asia-Pacific markets, and risk contagion is from the European and American developed markets to the Asia-Pacific regions. The study further identifies implied volatility index and market liquidity as the main positive determinants of risk spillover, which are robust across different rolling window lengths and horizons. We also find that the explanatory power is more significant during financial crises. • High-frequency data is used to analyze global asymmetric volatility spillover effects. • Over time, downside risk spillover surpasses upside risk spillover significantly. • Risk contagion is from the developed markets to the Asia-pacific regions. • Developed markets connected better than emerging markets. • VIX and market liquidity in risk-transmitting markets drive volatility spillover. [ABSTRACT FROM AUTHOR]

• CIC-Gal nanomissiles were constructed by dual-coordination-driven self-assembly. • CIC-Gal nanomissiles showed prominent size/charge dual-transformability function. • CIC-Gal nanomissiles achieved synergistic chemotherapy/PDT/PTT in HCC. • CIC-Gal nanomissiles could induce ICD and promote CD8+ T cell infiltration into HCC. • CIC-Gal/αPD-1 combination activated robust systemic antitumor immunity in HCC. PD-1 blockade therapy holds great potential for curing hepatocellular carcinoma (HCC), but its efficacy is severely restrained by inefficient CD8+ T cells and abundant immunosuppressive myeloid-derived suppressor cells (MDSCs) in tumors. Moreover, the solid feature of HCC limits drugs' penetration depth. Herein, cisplatin/indocyanine green (ICG)-coloaded polysaccharide-based nanomissiles (CIC-Gal) with galactose-mediated tumor targeting ability and tumor microenvironment (TME)-responsive size/charge dual-transformability are constructed by coordination-driven self-assembly. The nanoparticles can efficiently accumulate in tumors and exert antitumor effects on HCC via combinational chemotherapy/phototherapy. Importantly, CIC-Gal nanoparticles may protect cisplatin from glutathione-mediated detoxification by depleting glutathione. Photodynamic therapy rather than photothermal therapy plays a predominant role in ICG-mediated phototherapy. Furthermore, CIC-Gal nanoparticles can induce prominent immunogenic cell death (ICD), promote dendritic cells maturation, and activate robust systemic antitumor immunity in combination with αPD-1, which efficiently eradicates primary tumors, inhibits distant tumor growth and lung metastasis, and prolongs survival of tumor-bearing mice by promoting CD8+ T cell infiltration in tumors, suppressing the expansion and trafficking of MDSCs, and reshaping immunostimulatory TME. Collectively, this study provides a drug-based coordination-driven polysaccharide nanomissile construction approach, and the CIC-Gal nanoparticles display a strong immunomicroenvironment-reeducating ability for potentiating HCC immunotherapy. [ABSTRACT FROM AUTHOR]

This paper investigates the impacts of personalized individual semantics (PIS) on consistency and consensus in Best–Worst method (BWM) with heterogeneous linguistic preference information. Firstly, a PIS driven consistency measurement and information transformation method is presented to analyze the consistency level of linguistic preference information (i.e., best-to-others and others-to-worst vectors) of each decision maker, and this is conducted by maximizing the consistency level of additive preference relation that converted from linguistic preference information via personalized numerical scales. Secondly, a PIS driven maximum consensus optimization model within the BWM framework is designed to yield the maximum consensus level among the additive preference relations generated from heterogeneous linguistic preference information by means of personalized numerical scales. Thirdly, a PIS-based heterogeneous linguistic consensus reaching process is put forward to promote the consensus establishment among decision makers. Finally, the validity of the proposed BWM framework is verified by a case study, a sensitive analysis, and a comparison analysis. [ABSTRACT FROM AUTHOR]

[Display omitted] Immune checkpoint blockade (ICB)-based immunotherapy is a revolutionary therapeutic strategy for hepatocellular carcinoma (HCC). However, tumor immune tolerance and escape severely restrict the therapeutic efficacy of ICB therapy. It is urgent to explore new strategies to potentiate ICB therapy in HCC. Herein, we developed manganese oxide-crosslinked bovine albumin/hyaluronic acid nanoparticles (BHM) by an innovative hydrazide-manganese coordination and desolvation process. Successive loading of doxorubicin (DOX) and indocyanine green (ICG) was achieved via hydrazone linkage and electrostatic interactions, respectively, obtaining DOX/ICG-coloaded BHM nanoplatform (abbreviated as BHMDI). The BHMDI nanoplatform exhibited a high drug content (>46%) and pH/reduction dual-responsive drug release behavior. The nanoplatform could efficiently alleviate tumor hypoxia by catalytic decomposition of intracellular H 2 O 2 to O 2 and significantly improve BHMDI-based photodynamic chemotherapy efficacy. The BHMDI nanoplatform downregulated the proportion of alternatively activated (M2) macrophages in tumors and simultaneously induced immunogenic death of HCC cells, thus promoting the maturation of dendritic cells and ensuing priming of CD4+ and CD8+ T cells. Importantly, programmed death-1 (PD-1) blockade in combination with BHMDI nanoplatform not only eradicated primary tumors but inhibited tumor recurrence, abscopal tumor growth and lung metastasis of HCC by triggering robust systemic antitumor immunity. This work proved the feasibility of BHMDI-based photodynamic chemotherapy for potentiating PD-1 blockade immunotherapy by reversing hypoxic and immunosuppressive tumor microenvironment. [ABSTRACT FROM AUTHOR]

[Display omitted] Immune checkpoint blockade (ICB)-based immunotherapy is a revolutionary therapeutic strategy for hepatocellular carcinoma (HCC). However, tumor immune tolerance and escape severely restrict the therapeutic efficacy of ICB therapy. It is urgent to explore new strategies to potentiate ICB therapy in HCC. Herein, we developed manganese oxide-crosslinked bovine albumin/hyaluronic acid nanoparticles (BHM) by an innovative hydrazide-manganese coordination and desolvation process. Successive loading of doxorubicin (DOX) and indocyanine green (ICG) was achieved via hydrazone linkage and electrostatic interactions, respectively, obtaining DOX/ICG-coloaded BHM nanoplatform (abbreviated as BHMDI). The BHMDI nanoplatform exhibited a high drug content (>46%) and pH/reduction dual-responsive drug release behavior. The nanoplatform could efficiently alleviate tumor hypoxia by catalytic decomposition of intracellular H 2 O 2 to O 2 and significantly improve BHMDI-based photodynamic chemotherapy efficacy. The BHMDI nanoplatform downregulated the proportion of alternatively activated (M2) macrophages in tumors and simultaneously induced immunogenic death of HCC cells, thus promoting the maturation of dendritic cells and ensuing priming of CD4+ and CD8+ T cells. Importantly, programmed death-1 (PD-1) blockade in combination with BHMDI nanoplatform not only eradicated primary tumors but inhibited tumor recurrence, abscopal tumor growth and lung metastasis of HCC by triggering robust systemic antitumor immunity. This work proved the feasibility of BHMDI-based photodynamic chemotherapy for potentiating PD-1 blockade immunotherapy by reversing hypoxic and immunosuppressive tumor microenvironment. [ABSTRACT FROM AUTHOR]

Polyketide synthase 13 (Pks13), an essential enzyme for the survival of Mycobacterium tuberculosis (Mtb), is an attractive target for new anti-TB agents. In our previous work, we have identified 2-phenylindole derivatives against Mtb. The crystallography studies demonstrated that the two-position phenol was solvent-exposed in the Pks13-TE crystal structure and a crucial hydrogen bond was lost while introducing bulkier hydrophobic groups at indole N moieties. Thirty-six N-phenylindole derivatives were synthesized and evaluated for antitubercular activity using a structure-guided approach. The structure–activity relationship (SAR) studies resulted in the discovery of the potent Compounds 45 and 58 against Mtb H37Rv, with an MIC value of 0.0625 μg/mL and 0.125 μg/mL, respectively. The thermal stability analysis showed that they bind with high affinity to the Pks13-TE domain. Preliminary ADME evaluation showed that Compound 58 displayed modest human microsomal stability. This report further validates that targeting Pks13 is a valid strategy for the inhibition of Mtb and provides a novel scaffold for developing leading anti-TB compounds. [ABSTRACT FROM AUTHOR]

Dynemicin is an enediyne natural product from Micromonospora chersina ATCC53710. Access to the biosynthetic gene cluster of dynemicin has enabled the in vitro study of gene products within the cluster to decipher their roles in assembling this unique molecule. This paper reports the crystal structure of DynF, the gene product of one of the genes within the biosynthetic gene cluster of dynemicin. DynF is revealed to be a dimeric eight‐stranded β‐barrel structure with palmitic acid bound within a cavity. The presence of palmitic acid suggests that DynF may be involved in binding the precursor polyene heptaene, which is central to the synthesis of the ten‐membered ring of the enediyne core. [ABSTRACT FROM AUTHOR]

Polysaccharide hydrogels are promising candidate matrices for recapitulating the characteristics of extracellular matrix (ECM) in breast tumors in terms of their structure and composition. Herein, to obtain an ECM-mimetic matrix, hydroxyethyl chitosan (HECS) hydrogels were prepared through Schiff-base crosslinking reaction using dialdehyde hyaluronic acid as crosslinker. The obtained HECS hydrogels displayed a highly porous structure, a stiffness comparable to that of breast tissue, and a fast water-absorption speed. The amount of crosslinker had great effects on the swelling and rheological behaviors of the HECS hydrogels. Preliminary results from in vitro biological assessments confirmed that MCF-7 cells incubated within HECS hydrogels preferred to grow into three-dimensional spheroids. Importantly, the cells displayed enhanced migrative capability and upregulated expression levels of MMP-2, TGF-β and VEGF in comparison to two-dimension cultured cells. Hence, the HECS hydrogels show great promise as a biomimetic ECM in constructing breast tumor models. [ABSTRACT FROM AUTHOR]

Spasmolytic polypeptide-expressing metaplasia (SPEM) is characterized by mucus cell morphologies at the base of gastric glands, which is considered advanced SPEM when accompanied with an increase in transcripts associated with intestinal-type gastric cancer. Weiwei decoction (WWD) was modified from "Si-Jun-Zi Tang," which has been used for thousands of years in China against gastric atrophy and metaplasia. To investigate the effects and potential mechanisms of WWD against advanced SPEM. Liquid chromatography-mass spectrometry was employed to analyze the constituents of WWD. Five-month-infected Helicobacter pylori (H. pylori) Sydney strain 1 C57BL/6J mice and 6-week-old ATPase H+/K+ transporting subunit alpha-knockout mice (Atp4a −/−) were given folic acid (1.95 mg/kg) or WWD (13.65 g/kg, 27.30 g/kg, 54.60 g/kg) by gavage for one month. WWD demonstrated beneficial effects on gastric mucosal pathology and mucus secretion. In H. pylori -infected mice, WWD effectively reduced the expression of GSII and inhibited the mRNA levels of key markers associated with advanced SPEM, including Clu , Cftr , Wfdc2 , Dmbt1 , and Gpx2. Similarly, in Atp4a −/− mice, WWD significantly decreased the expressions of GSII and Clusterin, and inhibited the mRNA levels of Wfdc2 , Cftr , Dmbt1 , and Gpx2. Notably, WWD restored the expression of markers for chief cells (PGC, GIF) and parietal cells (ATP4A), particularly in the medium- and high-dose groups, indicating its potential anti-atrophy effect on H. pylori -infected and Atp4a −/− mice. WWD administration resulted in a decline in TFF2 expression to baseline levels, suggesting that the mucous protection mediated by TFF2 was unaffected. Furthermore, the infiltration of CD163+F4/80+ M2 macrophages in the gastric mucosa of H. pylori -infected mice was reduced after WWD treatment, indicating a potential modulatory role of WWD on M2 macrophages. WWD exerted protective effects against SPEM in H. pylori -infected and Atp4a −/− mice. The optimal doses of WWD were found to be medium doses in H. pylori -infected mice and high doses in Atp4a −/− mice. These effects include inhibition of transcripts associated with intestinal-type gastric adenocarcinoma, restoration of ATP4A and PGC expression, and reduction of M2 macrophage infiltration. These findings provide valuable insights into the therapeutic effects of WWD on advanced SPEM and highlight its potential as a treatment option. [Display omitted] • Weiwei decoction (WWD) has been used in treating gastric atrophy and metaplasia in China for over 20 years. • This study investigates WWD's effects against advanced Spasmolytic polypeptide-expressing metaplasia (SPEM) in mice. • WWD improves gastric mucosal pathology and suppresses intestinal-type gastric adenocarcinoma-associated transcripts. • WWD has the potential to restore ATP4A and PGC expression, decrease M2 macrophage infiltration, and protect against SPEM mice. [ABSTRACT FROM AUTHOR]

UBE2T is an E2 ubiquitin ligase critical for ubiquitination of substrate and plays important roles in many diseases. Despite the important function, UBE2T is considered as an undruggable target due to lack of a pocket for binding to small molecules with satisfied properties for clinical applications. To develop potent and specific UBE2T inhibitors, we adopted a high-throughput screening assay and two compounds-ETC-6152 and ETC-9004 containing a sulfone tetrazole scaffold were identified. Solution NMR study demonstrated the direct interactions between UBE2T and compounds in solution. Further co-crystal structures reveal the binding modes of these compounds. Both compound hydrolysation and formation of a hydrogen bond with the thiol group of the catalytic cysteine were observed. The formation of covalent complex was confirmed with mass spectrometry. As these two compounds inhibit ubiquitin transfer, our study provides a strategy to develop potent inhibitors of UBE2T. • A HTS was performed against UBE2T and two inhibitors were identified. • UBE2T-inhibitor binding was investigated using NMR. • Co-crystal structures reals the inhibitor binding modes. • The mechanism of covalent inhibitors was determined. [ABSTRACT FROM AUTHOR]

The efficient catalytic activity and strong durability possibility of carbon-based three-dimensional fiber materials remains an important challenge in Electro-Fenton advanced oxidation technology. Graphite felt (GF) is a promising electrode material for 2-electron oxygen reduction reaction but with higher catalytic inertia. Anodizing modification of GF has been proved to enhance it electro-catalytic property, but the disadvantages of excessive or insufficient oxidation of GF need further improved. Herein, the surface reconstituted graphite felt by anodizing and HNO 3 ultrasonic integrated treatment was used as cathode to degrade norfloxacin (NOR) and the substantial role of different modification processes was essentially investigated. Compared with the single modification process, the synergistic interaction between these two methods can generate more defective active sites (DASs) on GF surface and greatly improved 2-electron ORR activity. The H 2 O 2 can be further co-activated by Fe2+ and DASs into •OH (ads and free) and •O 2 − to efficiently degrade NOR. The treated GF with 20 min anodizing and 1 h HNO 3 ultrasound had the highest electrocatalytic activity in a wide electric potential (−0.4 V to −0.8 V) and pH range (3–9) in system and the efficient removal rate of NOR was basically maintained after 5 cycles. Under optimal reaction conditions, 50 mg L−1 NOR achieved 93% degradation and almost 63% of NOR was completely mineralized within 120 min. The possible NOR degradation pathways and ecotoxicity of intermediates were analyzed by LC-MS and T.E.S.T. theoretical calculation. This paper provided the underlying insights into designing a high-efficiency carbon-based cathode materials for commercial antibiotic wastewater treatment. Mechanism of Electro-Fenton removal NOR by surface co-activation reconstruction graphite felt cathode. [Display omitted] • The edge and isomerism DASs were introduced on GF surface. • The co-activated GF enhanced NOR degradation with excellent reusability. • The EH-GF electrode had a wide electric potential and pH range for NOR removal. • The Fe2+ and DASs cooperatively transform H 2 O 2 into.•OH. • The removal mechanism, pathways, and ecotoxicity of NOR were analyzed. [ABSTRACT FROM AUTHOR]

• Nanozyme-assisted PDT nanoplatform was prepared by an innovative dual coordination. • Obtained nanoplatform showed tri-enzyme activity to potentiate ROS generation efficacy. • Obtained nanoplatform-mediated ROS storm could induce immunogenic cell death. • Nanoplatform/αPD-1 combination could induce robust systemic antitumor immunity. Induction of immunogenic tumor cell death (ICD) is a promising strategy to potentiate immune checkpoint blockade (ICB) efficacy. However, it is still a huge challenge to develop efficient ICD-inducing nanomedicine. Herein, a copper nanozyme-assisted photodynamic therapy (PDT) nanoplatform nHACI was developed to achieve efficient ICD induction and robust systemic antitumor immune response through amplifying intracellular oxidative stress. The nHACI was fabricated from hydrazided hyaluronan and Cu2+ through an innovative hydrazide-copper coordination and in situ mineralization process, followed by loading of photosensitizer indocyanine green (ICG) via ICG-copper coordination. The nHACI exhibited superior drug loading efficiency, tumor microenvironment-responsive degradation behavior, and Fenton-like, glutathione oxidase-like and catalase-like triple activities. Importantly, it could not only deplete glutathione and concurrently generate 1O 2 and ·OH that amplified oxidative stress and induced ICD but also downregulate the proportion of M2 macrophages in tumors. The combination of nHACI-based PDT and PD-1 blockade could efficiently eradicate primary tumors, inhibit distant tumor growth and lung metastasis, and prevent tumor recurrence, demonstrating activation of robust systemic antitumor immune response. Collectively, this study presents a novel coordination assembly approach and nHACI holds great potential in eradicating primary tumors and potentiating ICB therapy via inducing ICD. [ABSTRACT FROM AUTHOR]

This work investigated that the graphite felt anodized by NaOH, NH 4 HCO 3 , or H 2 SO 4 aqueous, and then as the cathode materials for in-situ hydrogen peroxide (H 2 O 2) production and its employed for rhodamine B (RhB) degradation via Electro-Fenton (EF) process. At −0.60 V (vs. SCE), after 120 min electrolysis, the H 2 O 2 yield by graphite felt which anodized by 0.2 M H 2 SO 4 achieved up 110.5 mg L−1 in 0.05 M Na 2 SO 4 electrolyte. Compared with the raw graphite felt used for cathode, the H 2 O 2 yield increased by 15.85 times under the same conditions. The results of Raman spectroscopy demonstrated that graphite felt anodized by H 2 SO 4 solution can be achieved the highest defect degree. For the degradation of RhB, the cathode which anodized by H 2 SO 4 solution has the highest removal rate. For the degradation rate of RhB, the effect of applied current density, Fe2+ ions concentration, pH value were investigated. In addition, suggested that the efficient Fe3+ reduction reaction on the cathode surface was an important reason of the high efficiency of RhB degradation. 5-times continuous runs indicated that the modified cathode has remarkable stability and reusability during the EF process. [Display omitted] • Graphite felt modified by anodic oxidation used for the cathode of Electro-Fenton technology. • Modification significantly improved the yield of H 2 O 2 and the degradation rate of RhB. • The effect of solution types of electrolyte on graphite felt modification was studied. • Investigated the effect factors of current density, Fe2+ concentration, pH for RhB removal rate. [ABSTRACT FROM AUTHOR]

It is still a huge challenge for concurrent highly efficient loading of chemotherapeutic agent and photosensitizer into single nanocarrier via stimuli-responsive linkages due to their different physicochemical properties and pharmacokinetics. Herein, based on the discovery of unique cisplatin-hydrazide and cisplatin-indocyanine green (ICG) coordination reactions, a multifunctional coordination nanoprodrug, cisplatin/ICG co-loaded hydrazided hyaluronan/bovine serum albumin (HBCI) nanoparticles, was developed by a desolvation-dual coordination process. The nanoprodrug exhibited ultrahigh drug loading efficiency and glutathione/NIR light dual-responsive drug release behavior. In vitro cellular studies demonstrated efficient internalization and apoptosis-inducing ability of the nanoprodrug in HepG2 cells. In vivo results confirmed the efficacious tumor accumulation and biosafety of HBCI nanoprodrug and synergistic effect of HBCI-based combined photodynamic chemotherapy on inhibiting tumor growth. Overall, this work not only provides a novel dual coordination approach for highly efficient loading of cisplatin and ICG but also verifies the therapeutic potential of HBCI nanoprodrug in combating hepatocellular carcinoma. [Display omitted] [ABSTRACT FROM AUTHOR]