Tailoring Oxygen Reduction Reaction Kinetics of Fe-N-C Catalyst via Spin Manipulation for Efficient Zinc-Air Batteries.

The interaction between oxygen species and metal sites of various orbitals exhibits intimate correlation with the oxygen reduction reaction (ORR) kinetics. Herein, a new approach for boosting the inherent ORR activity of atomically dispersed Fe-N-C matrix is represented by implanting Fe atomic clusters nearby. The as-prepared catalyst delivers excellent ORR activity with half-wave potentials of 0.78 and 0.90 V in acidic and alkaline solutions, respectively. The decent ORR activity can also be validated from the high-performance rechargeable Zn-air battery. The experiments and density functional theory calculations reveal that the electron spin-state of monodispersed Fe active sites is transferred from the low spin (LS, t2g 6 eg 0) to the medium spin (MS, t2g 5 eg 1) due to the involvement of Fe atomic clusters, leading to the spin electron filling in σ∗ orbit, by which it favors OH- desorption and in turn boosts the reaction kinetics of the rate-determining step. This work paves a solid way for rational design of high-performance Fe-based single atom catalysts through spin manipulation.

Selective degradation of PL2L60 by metabolic stresses­induced autophagy suppresses multi­cancer growth.

It has been reported that PL2L60 proteins, a product of PIWIL2 gene which might be activated by an intragenic promoter, could mediate a common pathway specifically for tumorigenesis. In the present study, it was further identified by using western blot assay that the PL2L60 proteins could be degraded in cancer cells through a mechanism of selective autophagy in response to oxidative stress. The PL2L60 was downregulated in various types of cancer cells under the hypoxic condition independently of HIF­1α, resulting in apoptosis of cancer cells. Inhibition of autophagy by small interfering RNA targeting of either Beclin­1 (BECN1) or Atg5 resulted in restoration of PL2L60 expression in hypoxic cancer cell. The hypoxic degradation of PL2L60 was also blocked by the attenuation of the autophagosome membrane protein Atg8/microtubule­associated protein 1 light chain 3 (LC3) or autophagy cargo protein p62 expression. Surprisingly, Immunofluorescence analysis demonstrated that LC3 could be directly bound to PL2L60 and was required for the transport of PL2L60 from the nucleus to the cytoplasm for lysosomal flux under basal or activated autophagy in cancer cells. Moreover, flow cytometric analysis displayed that knocking down of PL2L60 mRNA but not PIWIL2 mRNA effectively inhibited cancer cell proliferation and promoted apoptosis of cancer cells. The similar results were obtained from in vivo tumorigenic experiment, in which PL2L60 downregulation in necroptosis areas was confirmed by immunohistochemistry. These results suggested that various cancer could be suppressed by promoting autophagy. The present study revealed a key role of autophagic degradation of PL2L60 in hypoxia­induced cancer cell death, which could be used as a novel therapeutic target of cancer.

Research trends and hotspots of polyphyllin in high-incidence cancers: A bibliometric analysis.

Background: Polyphyllin, a natural compound derived primarily from the Paris genus, manifests its anticancer properties. Extensive research on its therapeutic potential in cancers has been reported. However, there is no systematical analysis of the general aspects of research on polyphyllin by bibliometric analysis. The aim of this study is to visualize emerging trends and hotspots and predict potential research directions in this field. Methods: In this study, we collected relevant research articles from the Web of Science Core Collection Bibliometrics. Using R-bibliometrix, we analyzed the research status, hotspots, frontiers, and development trends of polyphyllin in high-incidence cancers. To conduct a comprehensive visual analysis, CiteSpace and VOSviewer were used for visual analysis of authors, countries, institutions, keywords, and co-cited references within the published articles. Results: A total of 257 articles focusing on the research of polyphyllin in high-incidence cancers were retrieved from the WOSCC database, covering the period from 2005 to 2023. The analysis revealed a consistent increasing trend in annual publications during this timeframe. Notably, China emerged as the most productive country, with Tianjin University leading the institutions. The Journal of Ethnopharmacology stood out as the most prominent journal in this field, while Gao WY emerged as the most prolific author. Polyphyllin VI, polyphyllin II, and polyphyllin VII have emerged as the latest research hotspots. Additionally, the investigation of autophagy and its associated mechanisms has gained significant attention as a novel research direction. Conclusion: This study presents a novel visualization of the research on polyphyllin saponins in the field of highly prevalent cancers using bibliometric analysis. The investigation of polyphyllin D has emerged as a primary focus in this field, with lung cancer, breast cancer, and liver cancer being the key areas of current research. Lastly, polyphyllin saponins show potential application in the field of cancer.

Safety and feasibility of single-port nephroscopy combined with a needle electrode technique to treat dorsal SRCs.

Objective The aim of this study was to explore the safety and feasibility of single-port nephroscopy combined with a needle electrode technique to unroof single dorsal simple renal cysts (SRCs). Methods This was a retrospective analysis of the clinical data for 18 patients with single dorsal SRCs treated with single-port nephroscopy and a needle electrode technique at Zhongshan City People's Hospital from August 2021 to August 2022. The basic information included the cyst condition, surgical methods and recurrence rate, and follow-up was conducted with CT imaging. Results The surgery was successful in all 18 patients. The duration of surgery ranged from 24-46 minutes, with an average of 35.83±1.62 minutes; the intraoperative bleeding volume ranged from 2-20 ml, with an average of 9.0±1.3 ml; and the visual analog scale (VAS) score within 24 hours after surgery ranged from 1-6 points, with an average of 2.72±0.36 points. There were no significant postoperative complications, such as bleeding, urinary fistula, or infection. All drainage tubes were removed on the first day after surgery. After 1 year of postoperative follow-up, one patient experienced recurrence, for a recurrence rate of 5.6%. Conclusion Single-port nephroscopy combined with a needle electrode technique is a safe, feasible, and effective minimally invasive surgical approach for treating single dorsal SRCs.

A Comprehensive Analysis of Immunoglobulin E Levels, Allergen-Specific Sensitivities, and Clinical Manifestations in Allergic Dermatological Conditions: A Multicenter Retrospective Study in China.

Objective: To assess the correlations between Immunoglobulin E (IgE) levels, pruritus, and lesion severity in patients with eczema, atopic dermatitis, or urticaria. Methods: A retrospective study was conducted and data of 814 patients who visited the dermatology or allergy clinics of multiple hospitals, from December 2019 to December 2021, were collected. Patients were divided into children group (<18 years, 325 cases), adult group (18-60 years, 435 cases), and older population group (>60 years, 54 cases) based on the age. Baseline information, pruritus severity, severity of skin lesions, total IgE level, and specific IgE level were recorded to analyze the complex relationship between them. Results: The prevalence of allergic conjunctivitis and allergic rhinitis in the children group was significantly higher than that in the adult and older population group (P < 0.01 or P < 0.05). The positive rate of specific IgE in children group was significantly higher than that in the adult and older population group (P < 0.01). The IgE levels in children with moderate pruritus were significantly lower than those of severe pruritus (63.39vs 114.42 IU/mL, P < 0.05). The IgE levels in children with mild and moderate skin lesions were significantly lower than those in children with severe skin lesions (58.95 vs 72.88 vs 169.15 IU/mL, P < 0.001 or P < 0.01, respectively). Conclusion: Relationships among age, severity of skin pruritus and lesions, and allergen-specific IgE response are complex and subtle, displaying dynamic patterns.

The role of monocyte/macrophage chemokines in pathogenesis of osteoarthritis: A review.

Osteoarthritis (OA) is one of the most common degenerative diseases characterised by joint pain, swelling and decreased mobility, with its main pathological features being articular synovitis, cartilage degeneration and osteophyte formation. Inflammatory cytokines and chemokines secreted by activated immunocytes can trigger various inflammatory and immune responses in articular cartilage and synovium, contributing to the genesis and development of OA. A series of monocyte/macrophage chemokines, including monocyte chemotaxis protein (MCP)-1/CCL2, MCP2/CCL8, macrophage inflammatory protein (MIP)-1α/CCL3, MIP-1ß/CCL4, MIP-3α/CCL20, regulated upon activation, normal T-cell expressed and secreted /CCL5, CCL17 and macrophage-derived chemokine/CCL22, was proven to transmit cell signals by binding to G protein-coupled receptors on recipient cell surface, mediating and promoting inflammation in OA joints. However, the underlying mechanism of these chemokines in the pathogenesis of OA remains still elusive. Here, published literature was reviewed, and the function and mechanisms of monocyte/macrophage chemokines in OA pathogenesis were summarised. The symptoms and disease progression of OA were found to be effectively alleviated when the expression of these chemokines is inhibited. Elucidating these mechanisms could contribute to further understand how OA develops and provide potential targets for the early diagnosis of arthritis and drug treatment to delay or even halt OA progression.

BPKEM: A biometric-based private key encryption and management framework for blockchain.

The fundamental technology behind bitcoin, known as blockchain, has been studied and used in a variety of industries especially in finance. The security of blockchain is extremely important as it will affects the assets of the clients as well as it is the lifeline feature of the entire system that needs to be guaranteed. Currently, there is a lack of a methodical approach to guarantee the security and dependability of the private key during its whole life. Furthermore, there is no quick, easy, or secure way to create the encryption key. A biometric-based private key encryption and management framework (BPKEM) for blockchain is proposed not only to solve the private key lifecycle manag- ement problem, but also it maintains compatibility with existing blockchain systems. For the problem of private key encryption, a biometric-based stable key generation method is proposed. By using the relative invariance between facial and fingerprint feature points, this measure can convert feature points into stable and distinguishable descriptors, then using a reusable fuzzy extractor to create a stable key. The correct- ness and efficiency of the newly proposed biometric-based blockchain encryption tech- nique in this paper has been validated in the experiments.

Soil amendments alter cadmium distribution and bacterial community structure in paddy soils.

Soil amendments play a pivotal role in ensuring the safety of food production by inhibiting the transfer of heavy metal ions from soils to crops. Nevertheless, their impact on soil characteristics and the microbial community and their role in reducing cadmium (Cd) accumulation in rice remain unclear. In this study, pot experiments were conducted to investigate the effects of three soil amendments (mineral, organic, and microbial) on the distribution of Cd speciation, organic components, iron oxides, and microbial community structure. The application of soil amendments resulted in significant reductions in the soil available Cd content (16 %-51 %) and brown rice Cd content (16 %-78 %), facilitating the transformation of Cd from unstable forms (decreasing 10 %-20 %) to stable forms (increasing 77 %-150 %) in the soil. The mineral and organic amendments increased the soil cation exchange capacity (CEC) and plant-derived organic carbon (OC), respectively, leading to reduced Cd accumulation in brown rice, while the microbial amendment enhanced OC complexity and the abundances of Firmicutes and Bacteroidota, contributing to the decreased rice Cd uptake. The synchrotron radiation-based Fourier transform infrared (SR-FTIR) spectroscopy indicated that soil amendments regulated soil Cd species by promoting iron oxides and OC coupling. Moreover, both organic and microbial amendments significantly reduced the diversity and richness of the bacterial communities and altered their compositions and structures, by increasing the relative abundances of Bacteroidota and Firmicutes and decreasing those of Acidobacteria, Actinobacteria, and Myxococcota. Soil microbiome analysis revealed that the increase of Firmicutes and Bacteroidota associated with Cd adsorption and sequestration contributed to the suppression of soil Cd reactivity. These findings offer valuable insights into the potential mechanisms by which soil amendments regulate the speciation and bioavailability of Cd, and improve the bacterial communities, thereby providing guidance for agricultural management practices.

Prognostic and clinical significance of tumor-associated macrophages in esophageal squamous cell carcinoma after surgery: do biomarkers and distributions matter?

BACKGROUND: The role of tumor-associated macrophages (TAMs) in patients with esophageal squamous cell carcinoma (ESCC) following surgery remains controversial. Hence, we performed the present study to systematically analyze the prognostic and clinical significance of distinct TAMs biomarkers and distributions in ESCC patients underwent surgery. METHODS: PubMed, Web of Science, and EMBASE databases were searched up to March 31, 2023. The pooled analysis was conducted to evaluate the effects of TAMs on overall survival (OS), disease-free survival (DFS), and clinicopathological characteristics using fixed-effects or random-effect model. RESULTS: Involving a total of 2,502 ESCC patients underwent surgery from 15 studies, the results suggested that the total count of CD68+ TAMs was inversely associated with OS and DFS in ESCC patients, which was also noticed in the relationship of CD68+ TAMs in tumor islet (TI) with OS (all P<0.05), although no association between CD68+ TAMs in tumor stroma (TS) and OS (P>0.05). Moreover, either islet or stromal CD163+ TAMs density was a prognostic factor ESCC (all P<0.05). Similarly, an elevated CD204+ TAMs density in TI predicted a poor DFS (P<0.05), although CD204+ TAMs in TI had no relationship with OS (P>0.05). Besides, a high CD68+ TAMs density was significantly associated with lymphatic vessel invasion, vascular invasion, and lymph node metastasis (all P<0.05). CONCLUSION: Our results demonstrated the prognostic and clinical significance of TAMs in ESCC patients underwent surgery. TAMs should be considered a target that could improve prognostic stratification and clinical outcomes in ESCC after surgery.

Porous borders at the wild-crop interface promote weed adaptation in Southeast Asia.

High reproductive compatibility between crops and their wild relatives can provide benefits for crop breeding but also poses risks for agricultural weed evolution. Weedy rice is a feral relative of rice that infests paddies and causes severe crop losses worldwide. In regions of tropical Asia where the wild progenitor of rice occurs, weedy rice could be influenced by hybridization with the wild species. Genomic analysis of this phenomenon has been very limited. Here we use whole genome sequence analyses of 217 wild, weedy and cultivated rice samples to show that wild rice hybridization has contributed substantially to the evolution of Southeast Asian weedy rice, with some strains acquiring weed-adaptive traits through introgression from the wild progenitor. Our study highlights how adaptive introgression from wild species can contribute to agricultural weed evolution, and it provides a case study of parallel evolution of weediness in independently-evolved strains of a weedy crop relative.

Dendrobium Nobile Alcohol Extract Extends the Lifespan of Caenorhabditis elegans via hsf-1 and daf-16.

Dendrobium nobile is a traditional Chinese herb with anti-inflammatory, antioxidant, and neuroprotective properties. However, its antiaging effects are unclear. Herein, we studied the aging-related functions and the mechanism of action of the alcohol extract of Dendrobium nobile (DnAE) in the model organism Caenorhabditis elegans. The results indicated that 1 mg/mL DnAE slowed lipofuscin accumulation, decreased the levels of reactive oxygen species, elevated superoxide dismutase activity, enhanced oxidative and heat stress resistance, extended the lifespan of nematodes, protected their dopamine neurons from 6-hydroxydopamine-induced neurodegeneration, and reduced Aß-induced neurotoxicity. DnAE upregulated the mRNA expression of the transcription factors DAF-16 and HSF-1, promoted the nuclear localization of DAF-16, and enhanced the fluorescence intensity of HSP-16.2. However, it had no effect on the lifespan of DAF-16 mutants. Thus, DnAE can significantly extend lifespan, enhance heat stress tolerance, and delay age-related diseases through a DAF-16-dependent pathway.

Genomic and phenotypic signatures provide insights into the wide adaptation of a global plant invader.

Invasive alien species are primary drivers of biodiversity loss and species extinction. Smooth cordgrass (Spartina alterniflora) is one of the most aggressive invasive plants in coastal ecosystems around the world. However, the genomic bases and evolutionary mechanisms underlying its invasion success have remained largely unknown. Here, we assembled a chromosome-level reference genome and performed phenotypic and population genomic analyses between native US and introduced Chinese populations. Our phenotypic comparisons showed that introduced Chinese populations have evolved competitive traits, such as early flowering time and greater plant biomass, during secondary introductions along China's coast. Population genomic and transcriptomic inferences revealed distinct evolutionary trajectories of low- and high-latitude Chinese populations. In particular, genetic mixture among different source populations, together with independent natural selection acting on distinct target genes, may have resulted in high genome dynamics of the introduced Chinese populations. Our study provides novel phenotypic and genomic evidence showing how smooth cordgrass rapidly adapts to variable environmental conditions in its introduced ranges. Moreover, candidate genes related to flowering time, fast growth, and stress tolerance (i.e., salinity and submergence) provide valuable genetic resources for future improvement of cereal crops.

In-Situ Polymer Framework Strategy Enabling Printable and Efficient Perovskite Solar Cells by Mitigating "Coffee Ring" Effect.

Organic-inorganic hybrid perovskites are considered ideal candidates for future photovoltaic applications due to their excellent photovoltaic properties. Although solution-printed manufacturing has shown inherent potential for the low-cost, high-throughput production of thin-film semiconductor electronics, the high-quality and high-reproducibility deposition of large-area perovskite remains a bottleneck that restricts their commercialization due to the droplet coffee-ring effect (CRE). In this study, these issues are addressed by introducing an in situ polymer framework. The 3D framework formed by spontaneous cross-linking improves the precursor viscosity and homogenizes its heat diffusion coefficient, counteracting the lateral capillary flow of the colloidal particles and anchoring their flocculent movement. Thus, the Marangoni convection intensity is properly controlled to ensure high-quality perovskite films, which significantly enhances reproducibility in printing efficient photovoltaics by mitigating the CRE. Subsequently, the perovskite solar cells and modules achieve power conversion efficiencies of 23.94 and 17.53%, and exhibit positive environmental stability, retaining over 90 and 78% efficiency after storage for 2500 and 1600 h, respectively. This work may serves as a foundation for exploring precursor rheology to match the homogeneous deposition requirements of perovskite photovoltaics and facilitating the advancement of their printing manufacturing and commercialization transition.

A modified recombinant adenovirus vector containing dual rabies virus G expression cassettes confers robust and long-lasting humoral immunity in mice, cats, and dogs.

During the COVID-19 epidemic, the incidence of rabies has increased in several countries, especially in remote and disadvantaged areas, due to inadequate surveillance and declining immunization coverage. Multiple vaccinations with inactivated rabies virus vaccines for pre- or post-exposure prophylaxis are considered inefficient, expensive and impractical in developing countries. Herein, three modified human recombinant adenoviruses type 5 designated Adv-RVG, Adv-E1-RVG, and Adv-RVDG, carrying rabies virus G (RVG) expression cassettes in various combinations within E1 or E3 genomic regions, were constructed to serve as rabies vaccine candidates. Adv-RVDG mediated greater RVG expression both in vitro and in vivo and induced a more robust and durable humoral immune response than the rabies vaccine strain SAD-L16, Adv-RVG, and Adv-E1-RVG by more effectively activating the dendritic cells (DCs) - follicular helper T (Tfh) cells - germinal centre (GC) / memory B cells (MBCs) - long-lived plasma cells (LLPCs) axis with 100% survival after a lethal RABV challenge in mice during the 24-week study period. Similarly, dogs and cats immunized with Adv-RVDG showed stronger and longer-lasting antibody responses than those vaccinated with a commercial inactivated rabies vaccine and showed good tolerance to Adv-RVDG. In conclusion, our study demonstrated that simultaneous insertion of protective antigens into the E1 and E3 genomic regions of adenovirus vector can significantly enhance the immunogenicity of adenoviral-vectored vaccines, providing a theoretical and practical basis for the subsequent development of multivalent and multi-conjugated vaccines using recombinant adenovirus platform. Meanwhile, our data suggest Adv-RVDG is a safe, efficient, and economical vaccine for mass-coverage immunization.

[A Case of New Rapidly Progressing Ground-glass Nodule Lung Adenocarcinoma Near Primary Lesion after Stereotactic Body Radiation Therapy].

Ground-glass nodule (GGN) lung cancer often progresses slowly in clinical and there are few clinical studies on long-term follow-up of patients with operable GGN lung cancer treated with stereotactic body radiation therapy (SBRT). We present a successful case of GGN lung cancer treated with SBRT, but a new GGN was found in the lung adjacent to the SBRT target during follow-up. The nodule progressed rapidly and was confirmed as lung adenocarcinoma by surgical resection. No significant risk factors and related driving genes were found in molecular pathological findings and genetic tests. It deserves further study whether new GGN is related to the SBRT. This case suggests that the follow-up after SBRT should be vigilant against the occurrence of new rapidly progressive lung cancer in the target area and adjacent lung tissue.
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Efficacy and safety of CM310 in moderate-to-severe atopic dermatitis: A multicenter, randomized, double-blind, placebo-controlled phase 2b trial.

BACKGROUND: Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD. METHODS: This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied. RESULTS: At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs . placebo, 95% CI 31%-69%) and 45% (low vs . placebo, 95% CI 26%-64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator's Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. CONCLUSION: CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.

Rethinking Object Saliency Ranking: A Novel Whole-Flow Processing Paradigm.

Existing salient object detection methods are capable of predicting binary maps that highlight visually salient regions. However, these methods are limited in their ability to differentiate the relative importance of multiple objects and the relationships among them, which can lead to errors and reduced accuracy in downstream tasks that depend on the relative importance of multiple objects. To conquer, this paper proposes a new paradigm for saliency ranking, which aims to completely focus on ranking salient objects by their "importance order". While previous works have shown promising performance, they still face ill-posed problems. First, the saliency ranking ground truth (GT) orders generation methods are unreasonable since determining the correct ranking order is not well-defined, resulting in false alarms. Second, training a ranking model remains challenging because most saliency ranking methods follow the multi-task paradigm, leading to conflicts and trade-offs among different tasks. Third, existing regression-based saliency ranking methods are complex for saliency ranking models due to their reliance on instance mask-based saliency ranking orders. These methods require a significant amount of data to perform accurately and can be challenging to implement effectively. To solve these problems, this paper conducts an in-depth analysis of the causes and proposes a whole-flow processing paradigm of saliency ranking task from the perspective of "GT data generation", "network structure design" and "training protocol". The proposed approach outperforms existing state-of-the-art methods on the widely-used SALICON set, as demonstrated by extensive experiments with fair and reasonable comparisons. The saliency ranking task is still in its infancy, and our proposed unified framework can serve as a fundamental strategy to guide future work. The code and data will be available at https://github.com/MengkeSong/Saliency-Ranking-Paradigm.

Manipulation of Electron Spins with Oxygen Vacancy on Amorphous/Crystalline Composite-Type Catalyst.

By substituting the oxygen evolution reaction (OER) with the anodic urea oxidation reaction (UOR), it not only reduces energy consumption for green hydrogen generation but also allows purification of urea-rich wastewater. Spin engineering of the d orbital and oxygen-containing adsorbates has been recognized as an effective pathway for enhancing the performance of electrocatalysts. In this work, we report the fabrication of a bifunctional electrocatalyst composed of amorphous RuO2-coated NiO ultrathin nanosheets (a-RuO2/NiO) with abundant amorphous/crystalline interfaces for hydrogen evolution reaction (HER) and UOR. Impressively, only 1.372 V of voltage is required to attain a current density of 10 mA cm-2 over a urea electrolyzer. The increased oxygen vacancies in a-RuO2/NiO by incorporation of amorphous RuO2 enhance the total magnetization and entail numerous spin-polarized electrons during the reaction, which speeds up the UOR reaction kinetics. The density functional theory study reveals that the amorphous/crystalline interfaces promote charge-carrier transfer, and the tailored d-band center endows the optimized adsorption of oxygen-generated intermediates. This kind of oxygen vacancy induced spin-polarized electrons toward boosting HER and UOR kinetics and provides a reliable reference for exploration of advanced electrocatalysts.

RNA-binding protein hnRNPU regulates multiple myeloma resistance to selinexor.

Multiple myeloma (MM) is an incurable haematological cancer. Selinexor is the first-in-class selective inhibitor of nuclear export (SINE) and was newly approved for the treatment of MM. Until now, very few studies have investigated selinexor resistance in MM. Heterogeneous nuclear ribonucleoprotein U (hnRNPU) is an RNA-binding protein and a component of hnRNP complexes. Here we found that hnRNPU regulates MM sensitivity to selinexor. Cell apoptosis assays were performed to compare selinexor-induced cell death in control knockdown (CTR-KD) and hnRNPU knockdown (hnR-KD) MM cells. HnRNPU knockdown-induced nuclear protein retention was examined by proteomics array. HnRNPU-conferred mRNA translation regulation was evaluated by sucrose gradient assay, RNA electrophoresis mobility shift assay, and RNA pull-down assay. We found that hnR-KD MM cells were more sensitive to selinexor-induced cell death in vitro and in mouse model. MM patients who responded to selinexor had relatively low hnRNPU expression. In brief, hnRNPU comprehensively regulated MM sensitivity to selinexor by affecting the localization of LTV1 and NMD3, and mRNA translation of MDM2 and RAN, which were involved in XPO1-mediated nuclear export of ribosome subunits and tumor suppressors. Our discoveries indicate that hnRNPU might be a possible marker to categorize MM patients for the use of Selinexor.