A completely precious metal-free alkaline fuel cell with enhanced performance using a carbon-coated nickel anode.

SignificanceWe present a groundbreaking advance in completely nonprecious hydrogen fuel cell technologies achieving a record power density of 200 mW/cm2 with Ni@CNx anode and Co-Mn cathode. The 2-nm CNx coating weakens the O-binding energy, which effectively mitigates the undesirable surface oxidation during hydrogen oxidation reaction (HOR) polarization, leading to a stable fuel cell operation for Ni@CNx over 100 h at 200 mA/cm2, superior to a Ni nanoparticle counterpart. Ni@CNx exhibited a dramatically enhanced tolerance to CO relative to Pt/C, enabling the use of hydrogen gas with trace amounts of CO, critical for practical applications. The complete removal of precious metals in fuel cells lowers the catalyst cost to virtually negligible levels and marks a milestone for practical alkaline fuel cells.

Distinct roles for the Charcot-Marie-Tooth disease-causing endosomal regulators Mtmr5 and Mtmr13 in axon radial sorting and Schwann cell myelination.

The form of Charcot-Marie-Tooth type 4B (CMT4B) disease caused by mutations in myotubularin-related 5 (MTMR5; also called SET binding factor 1, SBF1) shows a spectrum of axonal and demyelinating nerve phenotypes. This contrasts with the CMT4B subtypes caused by MTMR2 or MTMR13 (SBF2) mutations, which are characterized by myelin outfoldings and classic demyelination. Thus, it is unclear whether MTMR5 plays an analogous or distinct role from that of its homolog, MTMR13, in the peripheral nervous system (PNS). MTMR5 and MTMR13 are pseudophosphatases predicted to regulate endosomal trafficking by activating Rab GTPases and binding to the phosphoinositide 3-phosphatase MTMR2. In the mouse PNS, Mtmr2 was required to maintain wild-type levels of Mtmr5 and Mtmr13, suggesting that these factors function in discrete protein complexes. Genetic elimination of both Mtmr5 and Mtmr13 in mice led to perinatal lethality, indicating that the two proteins have partially redundant functions during embryogenesis. Loss of Mtmr5 in mice did not cause CMT4B-like myelin outfoldings. However, adult Mtmr5-/- mouse nerves contained fewer myelinated axons than control nerves, likely as a result of axon radial sorting defects. Consistently, Mtmr5 levels were highest during axon radial sorting and fell sharply after postnatal day seven. Our findings suggest that Mtmr5 and Mtmr13 ensure proper axon radial sorting and Schwann cell myelination, respectively, perhaps through their direct interactions with Mtmr2. This study enhances our understanding of the non-redundant roles of the endosomal regulators MTMR5 and MTMR13 during normal peripheral nerve development and disease.

In Situ Insertion of Silicon Nanowires into Hollow Porous Co/NC Polyhedra Enabling Large-Current-Density Hydrogen Evolution Electrocatalysis.

N-doped carbon (NC)-encapsulated transition metal (TM) nanocomposites are considered as alternatives to Pt-based hydrogen evolution reaction (HER) electrocatalysts; however, their poor electron transfer and mass diffusion capability at high current densities hinder their practical application. Herein, an oriented coupling strategy for the in situ grafting of ultrafine Co nanoparticle-embedded hollow porous C polyhedra onto Si nanowires (Co/NC-HP@Si-NWs) is proposed to address this concern. Experimental investigations reveal that the intimate coupling between the Si-NW and Co/NC nanocage forms a multithreaded conductive network, lowering the energy barrier for internal electron transfer. When functionalized as an HER electrocatalyst in 0.5 m H2 SO4 , Co/NC-HP@Si-NWs deliver overpotentials as low as 57 and 440 mV at 10 and 500 mA cm-2 , respectively, which are much better than those of the pristine Co/NC-HP. Moreover, Co/NC-HP@Si-NWs show an outstanding cycle durability of 24 h at 10 and 500 mA cm-2 . The findings of this study are expected to inspire revolutionary work on the development of Si-mediated TM-based electrocatalysts for the HER.

Targeting tumor-infiltrating CCR8+ regulatory T cells induces antitumor immunity through functional restoration of CD4+ Tconvs and CD8+ T cells in colorectal cancer.

BACKGROUND: Chemokine (C-C motif) receptor 8 (CCR8) is a chemokine receptor selectively expressed on tumor-infiltrating regulatory T cells (Tregs). Strong immunosuppression mediated by CCR8+ Tregs observed in breast and lung malignancies suggest for their functional significance in cancer therapy. To date, detailed characterization of tumor-infiltrating CCR8+ Tregs cells in colorectal cancer (CRC) is limited. METHODS: To study the presence and functional involvement of CCR8+ Tregs in CRC, we analyzed the proportions of CCR8-expressing T cells in different T cell subsets in tumor and adjacent normal tissues and peripheral blood mononuclear cells (PBMCs) from CRC patients by Flow cytometry. Also, we compared the distribution of CCR8+ T cells in malignant tissues and peripheral lymphoid organs from a subcutaneous CRC murine model. Bioinformatic analysis was performed to address the significance of CCR8 expression levels in CRC prognosis, immune regulatory gene expression profiles and potential molecular mechanisms associated with CCR8+ Tregs in CRC tumors. Further, we administrated an anti-CCR8 monoclonal antibody to CT26 tumor-bearing mice and examined the antitumor activity of CCR8-targeted therapy both in vivo and in an ex vivo confirmative model. RESULTS: Here, we showed that Tregs was predominantly presented in the tumors of CRC patients (13.4 ± 5.8, p < 0.0001) and the CRC subcutaneous murine model (35.0 ± 2.6, p < 0.0001). CCR8 was found to be preferentially expressed on these tumor-infiltrating Tregs (CRC patients: 63.6 ± 16.0, p < 0.0001; CRC murine model: 65.3 ± 9.5, p < 0.0001), which correlated with poor survival. We found that majority of the CCR8+ Tregs expressed activation markers and exhibited strong suppressive functions. Treatment with anti-CCR8 antibody hampered the growth of subcutaneous CRC tumor through effectively restoring the anti-tumor immunity of CD4+ conventional T cells (CD4+ Tconvs) and CD8+ T cells, which was confirmed in the ex vivo examinations. CONCLUSIONS: Collectively, these findings illustrate the importance of CCR8+ Tregs for an immunosuppressive microenvironment in CRC tumors by functional inhibition of CD4+ Tconvs and CD8+ T cells, and suggest for the applicable value of CCR8-targeted therapy for CRC.

Improved Non-Negative Matrix Factorization-Based Noise Reduction of Leakage Acoustic Signals.

The detection of gas leaks using acoustic signals is often compromised by environmental noise, which significantly impacts the accuracy of subsequent leak identification. Current noise reduction algorithms based on non-negative matrix factorization (NMF) typically utilize the Euclidean distance as their objective function, which can exacerbate noise anomalies. Moreover, these algorithms predominantly rely on simple techniques like Wiener filtering to estimate the amplitude spectrum of pure signals. This approach, however, falls short in accurately estimating the amplitude spectrum of non-stationary signals. Consequently, this paper proposes an improved non-negative matrix factorization (INMF) noise reduction algorithm that enhances the traditional NMF by refining both the objective function and the amplitude spectrum estimation process for reconstructed signals. The improved algorithm replaces the conventional Euclidean distance with the Kullback-Leibler (KL) divergence and incorporates noise and sparse constraint terms into the objective function to mitigate the adverse effects of signal amplification. Unlike traditional methods such as Wiener filtering, the proposed algorithm employs an adaptive Minimum Mean-Square Error-Log Spectral Amplitude (MMSE-LSA) method to estimate the amplitude spectrum of non-stationary signals adaptively across varying signal-to-noise ratios. Comparative experiments demonstrate that the INMF algorithm significantly outperforms existing methods in denoising leakage acoustic signals.

In Situ Coupling of Carbon Dots with Co-ZIF Nanoarrays Enabling Highly Efficient Oxygen Evolution Electrocatalysis.

Metal-organic frameworks (MOFs) are regarded as one promising class of precatalysts for electrocatalytic oxygen evolution reaction (OER), yet most of them suffer from poor conductivity and lack of coordinatively unsaturated metal sites, which hinders the fast electrochemical reconstruction and thus a poor OER activity. To address this issue, a unique heterocomposite has been constructed by in situ inserting carbon dots (CDs) into cobalt-based zeolitic imidazolate framework (Co-ZIF) nanosheet arrays (Co-ZIF/CDs/CC) in the presence of carbon cloth (CC) via one-pot coprecipitation for alkaline OER. Benefiting from the synergism between CDs and Co-ZIF subunits such as superior conductivity, strong charge interaction as well as abundant metal sites exposure, the Co-ZIF/CDs/CC exhibits an enhanced promotion effect for OER and contributes to the deep phase transformation from CDs-coupled Co-ZIF to CDs-coupled active CoOOH. As expected, the achieved Co-ZIF/CDs/CC only requires an overpotential of 226 mV to deliver 10 mA cm-2 in 1.0 M KOH, which is lower than that of Co-ZIF/CC and superior to most previously reported CC-supported MOF precatalysts. Moreover, it can also maintain a large current density of 100 mA cm-2 for 24 h with negligible activity decay.

A 3D COF constructed by interlayer crosslinking of 2D COF as cathode material for lithium-sulfur batteries.

The design and construction of three-dimensional covalent organic frameworks (3D COF) remains a major challenge, and it is necessary to explore new strategies to synthesize 3D COF with ideal structure. Here, we utilize two-dimensional covalent organic framework (2D COF) with allyl side chain to achieve interlayer crosslinking through olefin metathesis reaction, thereby constructing a 3D COF with cage-like structures. This new material named CAGE-COF has larger specific surface area and more open pore structure than the original 2D COF. The cathode material with CAGE-COF retained 78.7% of its initial capacity after 500 cycles, and the fading rate is 0.04% each cycle.

Performance measurement of nonhomogeneous Hong Kong hospitals using directional distance functions.

Cook et al. (Oper Res 61(3):666-676, 2013) propose a DEA-based model for the performance evaluation of non-homogeneous decision making units (DMUs) based on constant returns to scale (CRS), extended by Li et al. (Health Care Manag Sci 22(2):215-228, 2019) to variable returns to scale (VRS). This paper locates these models into more general DDF models to deal with nonhomogeneous DMUs and applies these to Hong Kong hospitals. The production process of each hospital is divided into subunits which have the same inputs and outputs and hospital performance is measured using the subunits. The paper provides CRS and VRS versions of DDF models and compares them with Cook et al. (Oper Res 61(3):666-676, 2013) and Li et al. (Health Care Manag Sci 22(2):215-228, 2019). A kernel-based method is used to estimate the distributions as well as a DEA-based efficiency analysis adapted by Simar and Zelenyuk to test the distributions. Both DDF CRS and VRS versions produce results similar to Cook et al. (Oper Res 61(3):666-676, 2013) and Li et al. (Health Care Manag Sci 22(2):215-228, 2019) respectively. However, the statistical tests find differences for the different technologies assumed as would be expected. For hospital managers, the more generalised DDF models expand their range of options in terms of directional improvements and priorities as well as dealing with non-homogeneity.

Performance evaluation of regulatory schemes for retired electric vehicle battery recycling within dual-recycle channels.

As electric vehicles (EVs) are developing at a rapid pace, the foreseeable "scrap tide" of EV batteries poses a severe challenge to ecological protection. This article investigates a dual-recycle channel closed-loop supply chain and provides regulatory solutions to retired EV batteries' recycling. Specifically, we construct four supervision scenarios: S1 no policy intervention, S2 reward-penalty scheme, S3 deposit-refund scheme, and S4 dual scheme combining S2 and S3. Based on the Stackelberg game and empirical data, all scenarios' recycling performance is evaluated and compared with a view to "society, economy, and environment". The results revealed: (1) Compared with S1, the recycling rate and carbon reduction rate in S2∼S4 increase by 2.6049%/0.0092%, 4.0379%/0.0285%, and 6.6660%/0.0379%, respectively; (2) The difference between S2 and S3 in recycling performance depends on regulatory intensities, yet the latter places greater burdens on consumers and firms. The S4 presents optimal environmental performance but at the expense of socioeconomic development; (3) As regulatory intensity increases, social welfare rises driven by environmental benefits, then falls due to overburdened supply chain profits, consumer surplus, and policy expenditures; (4) Carbon trading prices and EVs' potential market sizes affect regulatory schemes' operations. Our results contribute to policy-making and managerial practices for EV battery recycling.

In situ surface enhanced Raman spectroscopy study of electrode-polyelectrolyte interfaces.

As polyelectrolytes play a more and more important role in electrochemical fields, further understanding of the electrode-polyelectrolyte interface is in high demand. Surface-enhanced Raman spectroscopy (SERS) is utilized widely in electrode-solution interface research due to its ultra-high sensitivity, but is still rarely in the study of the electrode-polyelectrolyte interface due to difficulties in constructing appropriate electrochemical in situ devices. Additionally, the reported electrochemical in situ Raman works on the electrode-polyelectrolyte interface have a common problem of the coexistence of electrode-solution interfaces and electrode-polyelectrolyte interfaces. Here, we used screen printing electrodes (SPE) with a compact planar three-electrode structure to carry out a new electrochemical in situ SERS test method, which was suitable for the study of the electrode-polyelectrolyte interface. Polyelectrolyte membranes can be conveniently and closely coated on the SPE's planar three electrodes to achieve isolated electrode-polyelectrolyte interfaces without electrode-solution interfaces coexisting. Strongly potential-dependent signals were obtained from the Pt-Nafion™ interface directly across the Nafion™ membrane, which verifies that this method is practical for the electrochemical in situ SERS study of the electrode-polyelectrolyte interface.

A novel data-driven decision model based on extended belief rule base to predict China's carbon emissions.

Global warming and climate change are gaining traction in recent years. As a major cause of global warming, carbon emissions were centered to China's climate change policy initiatives. Nevertheless, the existing policy discourse has yet reached a consensus on the optimal modeling method for carbon emissions prediction that is well-informed of both policy goals and the time-series pattern of carbon emissions. This paper fills the gap by promoting a novel data-driven decision model for carbon emissions prediction that is based on the extended belief rule base (EBRB) inference model. The new decision model consists of three components: 1) an indicator integration method, which aims to generate a few group indicators from a large number of statistical indicators; 2) a new EBRB construction method, which aims to consider the management policy goals for constructing EBRB; 3) a new ER-based inference method, which aims to predict carbon emissions based on time series change of relevant factors. The effectiveness of the proposed decision model has been tested against carbon emissions management data from 30 provinces in China. Experimental results demonstrate that the model will offer powerful reference value in the policy decision-making process, which will help to meet policy requirements for carbon emissions.

A novel behavioral three-way decision model with application to the treatment of mild symptoms of COVID-19.

The Coronavirus Disease 2019 (COVID-19) has popularized since late December 2019. In present, it is still highly transmissible and has severe impact on the public health and global economy. Due to the lack of specific drug and the appearance of different variants, the selection of the antiviral therapy to treat the patients with mild symptom is of vital importance. Hence, in this paper, we propose a novel behavioral Three-Way Decision (3WD) model and apply it to the medicine selection decision. First, a new relative utility function is constructed by considering the risk-aversion behavior and regret-aversion behavior of human beings. Second, based on the relative utility function, some new rules are defined to calculate the thresholds and conditional probabilities in 3WD and some corresponding theorems are explored and proved. Next, a new information fusion mechanism in the framework of evidential reasoning algorithm is developed. Then, the decision results are obtained based on the Bayesian decision procedure and the principle of maximum utility. Finally, an example with large-scale data set and an example about medicine selection for COVID-19 are provided to show the implementation process and effectiveness of the proposed method. Comparative analysis and sensitivity analysis are also performed to illustrate the superiority and the robustness of the current proposal.

A heterogeneous multi-attribute case retrieval method based on neutrosophic sets and TODIM for emergency situations.

Heterogeneous multi-attribute case retrieval is a crucial step in generating emergency alternatives during the course of emergency decision making (EDM) by referring to historical cases. This paper develops a heterogeneous multi-attribute case retrieval method for EDM that considers five attribute formats: crisp numbers, interval numbers, intuitionistic fuzzy numbers, single-valued neutrosophic numbers (SvNNs), and interval-valued neutrosophic numbers (IvNNs). First, we propose a similarity measurement of IvNNs and calculate the attribute similarities for the five attribute formats. The attribute weights are established using an optimal model. Next, the case similarities are calculated and the set of the similar historical cases is constructed. Furthermore, the evaluated information based on heterogeneous multi-attribute from similar historical cases is provided, and the calculation method for the evaluation of utility based on TODIM (an acronym for interactive and multi-criteria decision-making in Portugese) is proposed. The most suitable historical case is determined based on the case similarity and the evaluated utility. From this, the emergency alternative is generated. Finally, we demonstrate the efficacy of the proposed method with a case study and conduct comparisons against the performance of existing methods to assess the validity and superiority of the proposed method.

A non-RBM targeted RBD specific antibody neutralizes SARS-CoV-2 inducing S1 shedding.

Potent neutralizing antibodies (Abs) have been proven with therapeutic efficacy for the intervention against SARS-CoV-2. Majority of these Abs function by directly interfering with the virus entry to host cells. Here, we identified a receptor binding domain (RBD) specific monoclonal Ab (mAb) 82A6 with efficient neutralizing potency against authentic SARS-CoV-2 virus. As most Abs targeting the non-receptor binding motif (RBM) region, 82A6 was incapable to block the RBD-ACE2 interaction. In particular, it actively promoted the S1 subunit shedding from the S protein, which may lead to effective reduction of intact SARS-CoV-2 viruses. Importantly, it could block potential syncytia formation associated with post-infectious cell surface expression of S proteins. Our study evidenced a RBD specific Ab with unique beneficial efficacy against SARS-CoV-2 infection, which might bring informative significance to understand the collective effects of neutralizing Abs elicited in COVID-19 patients.

Discovery of potent glycogen synthase kinase 3/cholinesterase inhibitors with neuroprotection as potential therapeutic agent for Alzheimer's disease.

In the present work, a novel series of pyridinethiazole bearing benzylpiperidine hybrids were designed and synthesized as dual-target inhibitors of GSK-3ß/AChE. Among them, GD29 was the most promising candidate, with an IC50 value of 0.3 µM for hAChE and an IC50 value of 0.003 µM for hGSK-3ß, respectively. The compounds exhibited good drug-like properties with optimal inhibitory enzyme activities. Moreover, GD29 showed anti-inflammatory properties at micromolar concentrations and displayed interesting neuroprotective profiles in an in vitro model of oxidative stress-induced neuronal death. Notably, the compounds also exhibited good permeability across the blood-brain-barrier (BBB) both in vitro. Central cholinomimetic activity was confirmed using a scopolamine-induced cognition impairment model in Institute of Cancer Research (ICR) mice upon oral administration. The current work identified optimized compounds and explored the therapeutic potential of glycogen synthase kinase 3/cholinesterase inhibition for the treatment of AD.

Anti-cancer adjuvant drug screening via epithelial-mesenchymal transition-related aptamer probe.

Epithelial-mesenchymal transition (EMT) is implicated in the pathological processes of cancer metastasis and drug resistance. Anti-cancer drugs may also potentially lead to EMT, resulting in their reduced therapeutic effect. Therefore, the combination of these anti-cancer drugs with anti-EMT agents has been promoted in clinic. Screening anti-EMT drugs and evaluation of EMT process are highly dependent on EMT biomarkers on cell membrane. At present, the detection of EMT biomarker is mainly by Western blot method, which is time-consuming and complicated. In this work, for effectively screening anti-EMT drugs by evaluation of the EMT process, a type of aptamer probe based on aggregation-induced emission (AIE) was designed. The aptamer SYL3C was employed to target the EMT biomarker EpCAM on cell membrane. Two fluorophores, FAM and tetraphenylethene (TPE, an AIE dye), were modified at the two ends of SYL3C, respectively. This aptamer probe (TPE-SYL3C-FAM) can monitor the EpCAM expression, which can be recovered by anti-EMT drugs. By observation of the change in TPE emission intensity, the anti-EMT effect of drugs can be evaluated. The FAM emission was used as internal reference to reduce environmental interferences. This probe can be potentially used to screen anti-EMT agents as anti-cancer adjuvant drugs with high throughput.

Computational design of binder as the LC3-p62 protein-protein interaction.

Cellular autophagy is an intracellular degradation pathway, which transports damaged, deformed, senescent or non-functional proteins and organelles to lysosome for digestion and degradation. Cellular autophagy is deeply evolutionarily conservedfromyeasttomammaliancells, and many homologous proteins of the autophahgy regulators are found in several species. This physiological process maintains the steady state of cells. Furtheremore, autophagy dysfunction is closely related to various diseases, such as neurodegenerative diseases, inflammation-related diseases, cardiovascular diseases, metabolic diseases, etc. The LC3 and p62 protein protein interaction (PPI) promotes the formation of autophagosomes and delivers polyubiquitinated "cargoes" to autophagic degradation. Therefore, LC3-p62 PPI plays an integral role in the formation of autophagosomes and effectively inhibits autophagy. However, there are still few studies on the LC3-p62 PPI inhibitors for its unclear molecular mechanism. Furthermore, most of these inhibitors are macromolecules with poorly active, and small molecules are particularly scarce. In this article, the computation method was used to identify the hot spot and design peptides as the binder of LC3-p62 PPI. Findings from this work provide a reference for the follow-up research of discovering small molecule inhibitors targeting LC3-p62 PPI.

Measuring work complexity for acute care services.

Case weights capture the resource cost by diagnosis-related group (DRG) but may not fully reflect the complexity of the clinical services provided. This study describes the use of a work complexity index (WCI), for assessing acute care services focusing on those provided by physicians in healthcare systems. The services are classified using relative value units (RVUs) and their point value assigned using the resource-based relative value scale. 57,559 acute inpatients from a tertiary hospital were first classified into diagnosis-related groups, which together with the relative value units assigned to services were then used to calculate a work complexity index for 38 departments. A case mix index (CMI) was also compiled as a conventional measure of complexity which had a correlation of 0.676 (p < 0.001) with the WCI. The correlation between the WCI and the RVUs representing the weighted volume of physician activities was 0.342 (p = 0.036). The WCI represents a more output or activity focused measure of complexity whereas the CMI is more patient focused and thus provides better insights into Departments' productivity. Although this paper focuses on physicians, the WCI can be easily extended to include other clinical services.

Microwave Hydrothermally Synthesized Metal-Organic Framework-5 Derived C-doped ZnO with Enhanced Photocatalytic Degradation of Rhodamine B.

C-doped ZnO particles have been successfully prepared by the calcination using microwave hydrothermally prepared metal-organic framework-5 (MOF-5) as the precursor. MOF-5 was turned into C-doped ZnO through calcination at 500 °C, and its cubic shape was well-maintained. X-ray photoelectron spectroscopic studies confirmed the C-doping in the ZnO. The as-prepared C-doped ZnO demonstrated a Rhodamine B (RhB) degradation efficiency of 98% in 2 h under an solar-simulated light irradiation, much higher than that of C-doped ZnO derived from MOF-5 synthesized by the ordinary hydrothermal method. The trapping experiment revealed that the crucial factors in the RhB removal were photogenerated h+ and •O2-.

Two-Dimensional Ga2O3/C Nanosheets as Durable and High-Rate Anode Material for Lithium Ion Batteries.

The self-healing feature of gallium (Ga) is unique, making Ga-based materials attract attention for their potential to solve the anode pulverization issue of lithium ion batteries. In this work, a hierarchical two-dimensional (2D) Ga2O3/C structure has been synthesized by a facile NaCl template method. Ga2O3 nanoparticles (3.8 nm) are uniformly embedded in 2D carbon nanosheets. The long horizontal length of the carbon nanosheets (10 µm) provides long-range electron conductivity, and the thin vertical thickness (75 nm) shortens the Li ion diffusion path. Benefited from the integrated 2D structure and the high electron conductivity, the obtained 2D Ga2O3/C nanosheets exhibit excellent overall performance, including high lithium storage capacity (1026 mAh g-1 at 0.5 A g-1), high rate capability (378 mAh g-1 at 10.0 A g-1), and high cyclability (500 cycles at 0.5 A g-1). The lithiation/delithiation mechanism of 2D Ga2O3/C has been further studied with combined electrochemical and ex situ X-ray diffraction methods.