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Cameron defined the concept of generalized t $t$‐designs, which generalized t $t$‐designs, resolvable designs and orthogonal arrays. This paper introduces a new class of combinatorial designs which simultaneously provide a generalization of both generalized t $t$‐designs and group divisible t $t$‐designs. In certain cases, we derive necessary conditions for the existence of generalized group divisible t $t$‐designs, and then point out close connections with various well‐known classes of designs, including mixed orthogonal arrays, factorizations of the complete multipartite graphs, large sets of group divisible designs, and group divisible designs with (orthogonal) resolvability. Moreover, we investigate constructions for generalized group divisible t $t$‐designs and almost completely determine their existence for t=2,3 $t=2,3$ and small block sizes. [ABSTRACT FROM AUTHOR]

Construction of catalytic covalent organic frameworks (COFs) for oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is significant but rarely demonstrated. In this work, we have first constructed bifunctional COFs towards ORR and OER by integrating diarylamine derivatives into the Co‐porphyrin based frameworks. Both of the new COFs (CoTAPP‐PATA‐COF and CoTAPP‐BDTA‐COF) have good ordered structures, high surface areas, and robust chemical stability. The diarylamine units, as a typical electron donor and redox‐active cores, promote intramolecular electron transport along the frameworks and improve the electrochemically active surface areas. Thus, the COFs showed higher catalytic activities than that of the COF without redox‐active units. CoTAPP‐PATA‐COF had a halfwave potential of 0.80 V towards ORR, and delieved an overpotential of 420 mV for OER in 0.1 M KOH. The theoretical calculation revealed introducing diarylamine unites improved the oxygen electrocatalysis. [ABSTRACT FROM AUTHOR]

Construction of catalytic covalent organic frameworks (COFs) for oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is significant but rarely demonstrated. In this work, we have first constructed bifunctional COFs towards ORR and OER by integrating diarylamine derivatives into the Co‐porphyrin based frameworks. Both of the new COFs (CoTAPP‐PATA‐COF and CoTAPP‐BDTA‐COF) have good ordered structures, high surface areas, and robust chemical stability. The diarylamine units, as a typical electron donor and redox‐active cores, promote intramolecular electron transport along the frameworks and improve the electrochemically active surface areas. Thus, the COFs showed higher catalytic activities than that of the COF without redox‐active units. CoTAPP‐PATA‐COF had a halfwave potential of 0.80 V towards ORR, and delieved an overpotential of 420 mV for OER in 0.1 M KOH. The theoretical calculation revealed introducing diarylamine unites improved the oxygen electrocatalysis. [ABSTRACT FROM AUTHOR]

Phytohormone auxin plays a fundamental role in plant growth and defense against pathogens. However, how auxin signalling is regulated during virus infection in plants remains largely unknown. Auxin/indole‐3‐acetic acid (Aux/IAA) is the repressor of auxin signalling and can be recognized by an F‐box protein transport inhibitor response 1 (TIR1). Ubiquitination and degradation of Aux/IAA by SKP1‐Cullin‐F‐boxTIR1 (SCFTIR1) complex can trigger auxin signalling. Here, with an emerging important plant virus worldwide, we showed that tomato chlorosis virus (ToCV) infection or stable transgenic overexpression of its p22 protein does not alter auxin accumulation level but significantly decreases the expression of auxin signalling–responsive genes, suggesting that p22 can attenuate host auxin signalling. Further, p22 could bind the C‐terminal of SKP1.1 and compete with TIR1 to interfere with the SCFTIR1 complex assembly, leading to a suppression of Aux/IAA degradation. Silencing and over‐expression assays suggested that both NbSKP1.1 and NbTIR1 suppress ToCV accumulation and disease symptoms. Altogether, ToCV p22 disrupts the auxin signalling through destabilizing SCFTIR1 by interacting with the C‐terminal of NbSKP1.1 to promote ToCV infection. Our findings uncovered a previously unknown molecular mechanism employed by a plant virus to manipulate SCF complex–mediated ubiquitin pathway and to reprogram auxin signalling for efficient infection. Tomato chlorosis virus–encoded p22 protein can bind to the C‐terminal domain of SKP1 to interfere with the SCFTIR1 complex assembly, leading to suppressed auxin signalling and enhanced viral infection. Our findings unveil a new mechanism used by a plant virus to subvert ubiquitination to enhance infection. [ABSTRACT FROM AUTHOR]

Deubiquitylating enzymes (DUBs) maintain relative homeostasis of the cellular ubiquitome by removing the post‐translational modification ubiquitin moiety from substrates. Numerous DUBs have been demonstrated specificity for cleaving a certain type of ubiquitin linkage or positions within ubiquitin chains. Moreover, several DUBs perform functions through specific protein–protein interactions in a catalytically independent manner, which further expands the versatility and complexity of DUBs' functions. Dysregulation of DUBs disrupts the dynamic equilibrium of ubiquitome and causes various diseases, especially cancer and immune disorders. This review summarizes the Janus‐faced roles of DUBs in cancer including proteasomal degradation, DNA repair, apoptosis, and tumor metastasis, as well as in immunity involving innate immune receptor signaling and inflammatory and autoimmune disorders. The prospects and challenges for the clinical development of DUB inhibitors are further discussed. The review provides a comprehensive understanding of the multi‐faced roles of DUBs in cancer and immunity. [ABSTRACT FROM AUTHOR]

Research in clinical information retrieval has long been stymied by the lack of open resources. However, both clinical information retrieval research innovation and legitimate privacy concerns can be served by the creation of intrainstitutional, fully protected resources. In this article, we provide some principles and tools for information retrieval resource-building in the unique problem setting of patient-level information retrieval, following the tradition of the Cranfield paradigm. We further include an analysis of parallel information retrieval resources at Oregon Health & Science University and Mayo Clinic that were built on these principles. [ABSTRACT FROM AUTHOR]

This study presents an improved voltage shift islanding detection method with the new control mode. The proposed method adopts the modulation index shift scheme based on the pulse‐width modulation control principle, which can promote the detection performance in the multi‐inverter grid‐connected photovoltaic (PV) systems, compared with the conventional voltage positive feedback (VPF) method. The superposition algorithm of the proposed method can make the rapid reduction of voltage magnitude at the point of common coupling during the islanding condition, and minimise the non‐detection zone. Through the self‐varying positive feedback gain, the synchronisation of voltage shift rates from multiple PV inverters can be effectively improved under the varying active power conditions. According to the characteristic of maximum power point tracking control, the gain will be automatically changed along with the variable PV voltage. The advantage of the proposed method is analysed by the simulation results in comparison with the conventional VPF method. Moreover, the experimental results are provided to verify the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

Objectives: Executive function in people with depression is linked to the integrity of white matter fibers in the brain. We hypothesized that the maze tests in neuropsychological tests assessed reasoning and problem‐solving abilities dependent on the integrity of brain white matter fibers, and assessed this relationship using diffusion tensor imaging (DTI) in depressed patients and healthy controls. Methods: Participants aged from 18 to 50 years were recruited from Zhumadian Second People's Hospital from July 2018 to August 2019. The sample included 33 clinically diagnosed individuals with major depressive disorder (MDD) and 24 healthy volunteers (HVs). All subjects underwent Neuropsychological assessment battery (NAB) maze tests and DTI. Tract‐based spatial statistics technology in FSL software was used to process DTI data, and threshold‐free cluster enhancement (TFCE) was used to perform multiple comparison corrections. The fractional anisotropy (FA) of white matter fibers in the MDD group and HVs group were compared and extracted. Pearson correlation was used to analyze the relationship between FA and NAB scores and HAMD scores. Results: The mean NAB maze test score for the MDD group was lower than the HVs group, and the difference was statistically significant (F = 11.265, p =.037). The FA value of the body of corpus callosum and cerebral peduncle right in the depression group was lower than that in the healthy control group, and the difference was statistically significant (p <.05). FA value of the body of corpus callosum was positively correlated with NAB score (r = 0.400, p =.036), but not with the HAMD score (r = 0.065, p =.723). Conclusions: The decreased ability of reasoning and problem‐solving in MDD may be due to the decreased integrity of the white matter fibers of the body of the corpus callosum. [ABSTRACT FROM AUTHOR]

Suzuki-Miyaura coupling of heteroaryls is an important method for the preparation of compound libraries for medicinal chemistry and materials research. Although many catalysts have been developed, none of them have been generally applicable to the coupling reactions of heteroaryl chlorides and tosylates at room temperature. We discovered that a catalyst combination of Pd(OAc)2 and XPhos (2-dicyclohexylphosphanyl-2′,4′,6′-triisopropylbiphenyl) could efficiently catalyze these couplings. Besides the choice of catalyst, the use of hydroxide bases in an aqueous alcoholic solvent was essential for fast couplings. These conditions promoted fast release of active catalyst (XPhos)Pd0, and accelerated the transmetalation in the catalytic cycle. Most of the major families of heteroaryl chlorides (31 examples) and tosylates (17 examples) reached full conversion within minutes to hours at room temperature. The method could be easily scaled up for gram-scale synthesis. Furthermore, we examined the relative reactivity of coupling partners in whole reactions. Electron-rich heteroaryl chlorides and tosylates reacted more slowly than electron-deficient ones, in the order of indole, pyrrole < furan, thiophene < pyridine and other six-membered-ring azines. For heteroarylboronic acids, the reactivity ranking was reversed: indole, pyrrole > furan, thiophene > pyridine. Similarly, electron-deficient arylboronic acids were less reactive than electron-neutral and electron-rich ones. The reactivity trends from this study can help to choose appropriate coupling partners for Suzuki reactions. [ABSTRACT FROM AUTHOR]

The cover image is based on the Original Article Tomato chlorosis virus–encoded p22 suppresses auxin signalling to promote infection via interference with SKP1‐Cullin‐F‐boxTIR1 complex assembly by Sijia Liu et al., https://doi.org/10.1111/pce.14125. [ABSTRACT FROM AUTHOR]

Plants trigger a robust immune response by activating massive transcriptome reprogramming through crosstalk between PTI and ETI. However, how PTI and ETI contribute to the quantitative or/and qualitative output of immunity and how they work together when both are being activated were unclear. In this study, we performed a comprehensive overview of pathogen‐triggered transcriptomic reprogramming by analyzing temporal changes in the transcriptome up to 144 h after Colletotrichum gloeosporioides inoculated in Populus. Moreover, we constructed a hierarchical gene regulatory network of PagWRKY18 and its potential target genes to explore the underlying regulatory mechanisms of PagWRKY18 that are not yet clear. Interestingly, we confirmed that PagWRKY18 protein can directly bind the W‐box elements in the promoter of a transmembrane leucine‐rich repeat receptor‐like kinase, PagSOBIR1 gene, to trigger PTI. At the same time, PagWRKY18 functions in disease tolerance by modulation of ROS homeostasis and induction of cell death via directly targeting PagGSTU7 and PagPR4 respectively. Furthermore, PagPR4 can interact with PagWRKY18 to inhibit the expression of PagPR4 genes, forming a negative feedback loop. Taken together, these results suggest that PagWRKY18 may be involved in regulating crosstalk between PTI and ETI to activate a robust immune response and maintain intracellular homeostasis. Summary statement: Our research identifies a novel mechanism by which artificial expression of PagWRKY18 is sufficient to confer resistance to hemibiotrophic fungal pathogen Colletotrichum gloeosporioides, and provides insights into the poplar resistance breeding and generating transgenic resistance poplar lines. [ABSTRACT FROM AUTHOR]

Although numerous peroxidase (POD)‐like nanozymes have been designed for catalytic therapy of cancer, development of nanozymes with higher therapeutic efficacy and less adverse effects are challengeable. More importantly, the underlying antitumor mechanism remains largely unknown which hinders their application. Here, the nitrogen‐doped carbon nanozyme (N‐PCNS) as a model is utilized and demonstrated that its capacity to specifically activate the STING pathway in tumor cells through reactive oxgen species (ROS)‐mediated mitochondrial DNA (mtDNA) release, which provides the initial signals for STING‐dependent innate immune response. Further, a peptide‐nanozyme conjugate (PNEC, OPBP1‐N‐PCNS), comprising a PD‐L1 blocking/targeting dual‐functional peptide and a cationic‐coated N‐PCNS is constructed, which are conjugated through a matrix metalloproteinase responsive peptide linker. The cleaved derivate nanozyme with positive charge exhibits recyclable capacity and superior ability in capturing and enhancing the transcellular transport of tumor‐derived mtDNA toward DCs, thereby amplifying the STING signaling‐mediated anti‐tumor immune response. This study proposed a unique mechanism and design strategy for POD‐like nanozyme in cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Directed differentiation of bone‐marrow‐derived stem cells (BMSCs) toward chondrogenesis has served as a predominant method for cartilage repair but suffers from poor oriented differentiation tendency and low differentiation efficiency. To overcome these two obstacles, an injectable composite hydrogel that consists of collagen hydrogels serving as the scaffold support to accommodate BMSCs and cadmium selenide (CdSe) quantum dots (QDs) is constructed. The introduction of CdSe QDs considerably strengthens the stiffness of the collagen hydrogels via mutual crosslinking using a natural crosslinker (i.e., genipin), which simultaneously triggers photodynamic provocation (PDP) to produce reactive oxygen species (ROS). Experimental results demonstrate that the intensified stiffness and augmented ROS production can synergistically promote the proliferation of BMSCs, induce cartilage‐specific gene expression and increase secretion of glycosaminoglycan. As a result, this approach can facilitate the directed differentiation of BMSCs toward chondrogenesis and accelerate cartilage regeneration in cartilage defect repair, which routes through activation of the TGF‐β/SMAD and mTOR signaling pathways, respectively. Thus, this synergistic strategy based on increased stiffness and PDP‐mediated ROS production provides a general and instructive approach for developing alternative materials applicable for cartilage repair. [ABSTRACT FROM AUTHOR]

Mesothelioma (MESO) is an infrequent tumor derived from mesothelial cells of pleura, peritoneum, pericardium, and tunica vaginalis testis. Despite advancement in technologies and better understanding of tumor progression mechanism, the prognosis of MESO remains poor. The role of alternative splicing events (ASEs) in the oncogenesis, tumor metastasis and drug resistance has been widely discussed in multiple cancers. But the prognosis and potential therapeutic value of ASEs in MESO were not clearly studied by now. We constructed a prognostic model using RNA sequencing data and matched ASE data of MESO patients obtained from the TCGA and TCGASpliceSeq database. A total of 3,993 ASEs were identified associated with overall survival using Cox regression analysis. Eight of them were finally figured out to institute the model by lasso regression analysis. The risk score of the model can predict the prognosis independently. Among the identified 390 splicing factors (SF), HSPA1A and DDX3Y was significantly associated with 43 OS‐SEs. Among these OS‐SEs, SNX5‐58744‐AT (p = 0.048) and SNX5‐58745‐AT (p = 0.048) were significantly associated with bone metastasis. Co‐expression analysis of signal pathways and SNX5‐58744‐AT, SNX5‐58745‐AT was also depicted using GSVA. Finally, we proposed that splicing factor (SF) HSPA1A could regulate SNX5‐58744‐AT (R = −0.414) and SNX5‐58745‐AT (R = 0.414) through the pathway "Class I MHC mediated antigen processing and presentation" (R = 0.400). In this way, tumorigenesis and bone metastasis of MESO were controlled. [ABSTRACT FROM AUTHOR]

Background: A subset of patients with hypertrophic cardiomyopathy (HCM) is at high risk of sudden cardiac death (SCD). Practice guidelines endorse use of a risk calculator, which requires entry of left atrial (LA) diameter. However, American Society of Echocardiography (ASE) guidelines recommend the use of LA volume index (LAVI) for routine quantification of LA size. The aims of this study were to (a) develop a model to estimate LA diameter from LAVI and (b) evaluate whether substitution of measured LA diameter by estimated LA diameter derived from LAVI reclassifies HCM‐SCD risk. Methods: The study cohort was comprised of 500 randomly selected HCM patients who underwent transthoracic echocardiography (TTE). LA diameter and LAVI were measured offline using digital clips from TTE. Linear regression models were developed to estimate LA diameter from LAVI. A European Society of Cardiology endorsed equation estimated SCD risk, which was measured using LA diameter and estimated LA diameter derived from LAVI. Results: The mean LAVI was 48.5 ± 18.8 mL/m2. The derived LA diameter was 45.1 mm (SD: 5.5 mm), similar to the measured LA diameter (45.1 mm, SD: 7.1 mm). Median SCD risk at 5 years estimated by measured LA diameter was 2.22% (interquartile range (IQR): 1.39, 3.56), while median risk calculated by estimated LA diameter was 2.18% (IQR: 1.44, 3.52). 476/500 (95%) patients maintained the same risk classification regardless of whether the measured or estimated LA diameter was used. Conclusions: Substitution of measured LA diameter by estimated LA diameter in the HCM‐SCD calculator did not reclassify risk. [ABSTRACT FROM AUTHOR]

Highly active oxygen evolution reaction (OER) electrocatalysts, such as those containing Fe, often face the challenge of severe dissolution of active elements. Addressing this concern through the establishment of a dynamically stable interface during OER presents a promising strategy, achieved by manipulation of catalyst components. Herein, the findings reveal that Fe loss during OER predominantly occurs during the initial activation phase, marked by irreversible structural distortion that disrupts interfacial dynamical stability. By investigating the structural evolution of Fe‐containing Prussian blue analogs, serving as a model OER precatalyst, the correlation between precatalyst structural changes and interfacial dynamic stability is elucidated. Utilizing thermal annealing of CoFe bimetal Prussian blue, favorable thermodynamic conditions are induced for generating cyano vacancies within the matrix, thereby facilitating enhanced initial activation during OER. Consequently, catalytically active and stable oxyhydroxide species rapidly form at the interface, exhibiting robust interactions with interfacial Fe elements to stabilize interface dynamics. Suppression of the irreversible structural distortion responsible for active element loss during initial activation culminates in enhanced OER activity and stability. [ABSTRACT FROM AUTHOR]

The present study investigated the difference of emotional stability between elders with long‐term tai chi experience and elders in a control group during the sequential risk‐taking task. Twenty‐eight tai chi practitioners (age = 67.36 ± 5.91 years, exercise years = 9.23 ± 4.19) and 28 control participants (age = 65.21 ± 3.55 years, other physical exercise without meditation component) participated in the experiment. Participants were asked to open a series of boxes consecutively and decided when to stop. Each box contained a reward, except for one, which contained a "devil." This box would eliminate the participant's score in the trial. Once participants stopped, both collected gains and missed chances were revealed. Then, participants rated how they felt on a 9‐point scale from extreme regret to extreme relief. Additionally, participants filled out the Chinese version of the Beck Depression Inventory, the Barratt Impulsiveness Scale Version 11, the NEO Five‐Factor Inventory, and the Five Facet Mindfulness Questionnaire. The tai chi group showed a higher meditation level, stronger emotional stability, and less risk propensity (all ps < .05) than the control group. In the tai chi group, meditation level was positively correlated with emotional stability (r = −.47, p < .01). Moreover, subjective emotion was negatively correlated with subsequent behavior (tai chi: β = −.44, p < .001; control: β = −.27, p <.001). Subjective emotion rating entirely mediated the relationship between objective outcome and subsequent behavioral change in the control group, whereas it partially mediated such relationship in the tai chi group. The current cross‐sectional study found a difference of behavior and feeling between elders with long‐term tai chi experience and elders in the control group, which suggests that long‐term tai chi experience could enhance elders' emotional stability and reduce their risk propensity during the sequential risk‐taking task. [ABSTRACT FROM AUTHOR]

Laser‐free photodynamic therapy (PDT) is a promising noninvasive therapeutic modality for deep‐seated tumor, yet is constrained by low efficiency due to the limited stimulation strategies. Herein, a novel miRNA‐responsive laser‐free PDT was developed through metal‐organic frameworks (MOFs)‐mediated chemiluminescence resonance energy transfer (CRET) nanoplatform. The photosensitizer chlorin e6 (Ce6)‐loaded MOFs were functionalized with hairpin nucleic acids for sensitive responsiveness of tumor biomarker miRNA through catalytic hairpin assembly (CHA), which enabled the amplified assembly of horseradish peroxidase (HRP)‐mimicking hemin/G‐quadruplex DNAzyme on MOFs. Simultaneously, the on‐MOF assembled DNAzymes efficiently catalyzed chemiluminescence reaction to stimulate adjacent Ce6 in the presence of luminol and H2O2, thus allowing the CRET‐mediated Ce6 luminescence and reactive oxygen species (ROS) generation for self‐illuminating PDT. The CRET nanoplatform achieved significant malignant cell apoptosis and tumor inhibition effects without external laser irradiation. It is envisioned that the miRNA‐amplified CRET nanoplatform might be a selective and highly efficient antitumor nanomedicine for precise theranostic. [ABSTRACT FROM AUTHOR]

Grasses possess basal and aerial axillary buds. Previous studies have largely focused on basal bud (tiller) formation but scarcely touched on aerial buds, which may lead to aerial branch development., Genotypes with and without aerial buds were identified in switchgrass ( Panicum virgatum), a dedicated bioenergy crop. Bud development was characterized using scanning electron microscopy. Microarray, RNA-seq and quantitative reverse transcription polymerase chain reaction ( RT-qPCR) were used to identify regulators of bud formation. Gene function was characterized by down-regulation and overexpression., Overexpression of miR156 induced aerial bud formation in switchgrass. Various analyses revealed that SQUAMOSA PROMOTER BINDING PROTEIN LIKE4 ( SPL4), one of the miR156 targets, directly regulated aerial axillary bud initiation. Down-regulation of SPL4 promoted aerial bud formation and increased basal buds, while overexpression of SPL4 seriously suppressed bud formation and tillering. RNA-seq and RT- qPCR identified potential downstream genes of SPL4., Unlike all previously reported genes acting as activators of basal bud initiation, SPL4 acts as a suppressor for the formation of both aerial and basal buds. The miR156- SPL4 module predominantly regulates aerial bud initiation and partially controls basal bud formation. Genetic manipulation of SPL4 led to altered plant architecture with increased branching, enhanced regrowth after cutting and improved biomass yield. [ABSTRACT FROM AUTHOR]

The article presents chemical equations on the article "Desymmetrization of Cyclic Olefins via Asymmetric Heck Reaction and Hydroarylation" by S. Liu and others, published in the 2013 issue of the "journal "Chemical Communications."

Background: Progestins are used as fertility‐sparing regimens for young patients with stage 1A endometrioid endometrial cancer (EEC) and atypical endometrial hyperplasia (AEH). CD163+ macrophages promote estrogen‐dependent EEC development, but whether they induce progestin insensitivity remains unclear. This study aimed to investigate the possible effects of CD163+ macrophages on progestin response in AEH/EEC patients. Methods: The number of infiltrating CD163+ macrophages in progestin‐insensitive and ‐sensitive endometrial lesions was compared. The effects of CD163+ macrophages on progestin responses and progesterone receptor (PR) expression in EC cells were evaluated in vitro. ATAC‐seq and RNA‐seq were combined to identify molecular/biological changes induced by CD163+ macrophages in progestin‐insensitive EC cells. Results: Increased CD163+ macrophage infiltration was significantly associated with progestin insensitivity and longer treatment durations in AEH/EEC patients. Additionally, the number of CD163+ macrophages was negatively correlated with PR expression in AEH/EEC tissues. Furthermore, the CD163+ macrophage‐mediated microenvironment and secreted cytokines downregulated PR expression and impaired the response of EC cells to medroxyprogesterone acetate (MPA). RNA‐seq analysis demonstrated that CD163+ macrophages antagonized PR signaling by blocking or even reversing MPA‐regulated differential gene expression. Based on RNA‐seq and ATAC‐seq analyses, extracellular matrix (ECM) signaling and ECM‐related transcription factors, FOXF2, POU1F1, and RUNX1were identified to potentially be involved in CD163+ macrophage‐induced progestin insensitivity in endometrial cancer patients. Conclusions: We identified CD163+ macrophages as an important mediator of progestin desensitization and an unfavorable factor for the efficacy of fertility‐preserving treatment in AEH/EEC patients. [ABSTRACT FROM AUTHOR]

A general protocol for the Suzuki coupling of both heteroaryl chlorides and tosylates with both aryl and heteroarylboronic acids as reaction partners is developed. [ABSTRACT FROM AUTHOR]

TGF‐β signaling is a key player in tumor progression and immune evasion, and is associated with poor response to cancer immunotherapies. Here, we identified ubiquitin‐specific peptidase 8 (USP8) as a metastasis enhancer and a highly active deubiquitinase in aggressive breast tumors. USP8 acts both as a cancer stemness‐promoting factor and an activator of the TGF‐β/SMAD signaling pathway. USP8 directly deubiquitinates and stabilizes the type II TGF‐β receptor TβRII, leading to its increased expression in the plasma membrane and in tumor‐derived extracellular vesicles (TEVs). Increased USP8 activity was observed in patients resistant to neoadjuvant chemotherapies. USP8 promotes TGF‐β/SMAD‐induced epithelial‐mesenchymal transition (EMT), invasion, and metastasis in tumor cells. USP8 expression also enables TβRII+ circulating extracellular vesicles (crEVs) to induce T cell exhaustion and chemoimmunotherapy resistance. Pharmacological inhibition of USP8 antagonizes TGF‐β/SMAD signaling, and reduces TβRII stability and the number of TβRII+ crEVs to prevent CD8+ T cell exhaustion and to reactivate anti‐tumor immunity. Our findings not only reveal a novel mechanism whereby USP8 regulates the cancer microenvironment but also demonstrate the therapeutic advantages of engineering USP8 inhibitors to simultaneously suppress metastasis and improve the efficacy of cancer immunotherapy. Synopsis: TGF‐β signaling is a key factor in tumor progression and is associated with poor response to cancer immunotherapy. This work shows that pharmacologically targeting the deubiquitinase USP8 can antagonise TGF‐β/SMAD signalling and improve the efficacy of cancer immunotherapy USP8 is a metastasis enhancer that directly deubiquitinates and stabilises TGF‐β receptor TβRII, thereby promoting TGF‐β/SMAD signaling.Gain of USP8 function promotes the secretion of TβRII+ circulating extracellular vesicles that induce CD8+ T cell exhaustion.Pharmacological inhibition of USP8 represses TGF‐β signalling and inhibits cancer progression.USP8 inhibition alleviates CD8+ T cell exhaustion and improves the efficacy of breast cancer immunotherapy. [ABSTRACT FROM AUTHOR]

In this work, the potassic rock (PR), an ore rich in aluminosilicate and alkali metal sources, was decomposed to active amorphous material in mild condition for the first time via sub-molten salt method. Low silica X (LSX) zeolite was successfully synthesized using the amorphous precursor from PRs as starting material. The effects of temperature, time, and mass concentration of alkali on the decomposition of PRs powder, and the effects of molar ratios of SiO2/Al2O3 and H2O/(Na2O + K2O) on the synthesis of LSX zeolite, were investigated. X-ray powder diffraction, scanning electron microscopy, energy dispersive X-ray spectrometer, and Fourier transform infrared spectroscopy were employed to characterize the precursors and as-prepared zeolites. The results indicated that the highly active amorphous precursor can be obtained in (Na, K)OH sub-molten salt medium with 80% of mass concentration of alkali at 190 °C for 3.0 h. The LSX zeolite can be synthesized in 5.85Na2O:1.65K2O:Al2O3:(2.1-2.3)SiO2:(113-125)H2O system using the slurry obtained from the decomposition of PRs. Copyright © 2016 Curtin University of Technology and John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Maximizing the Pt utilization is important for the widescale implementation of Pt‐based hydrogen evolution reaction (HER) electrocatalysts, owing to the scarcity of Pt. Here, three‐component heterostructured HER catalysts with ultrahigh Pt mass activity in which hollow PtCu alloy nanospheres are supported on an array of WO3 on Cu foam, are reported. It has been pointed out that the use of Pt counter electrode in a three‐electrode configuration in evaluating catalysts' HER performances in acidic media carries the risk of contaminating the working electrode in previous reports. Here, the authors rationally utilize this "contaminating" to "activate" low‐HER‐activity materials, maximizing the Pt utilization. As a result, ultrahigh Pt mass activity is achieved, that is 1.35 and 10.86 A mg−1Pt at overpotentials of 20 and 100 mV, respectively, 27 and 13 times higher than those of commercial Pt/C catalysts, outperforming some state‐of‐the‐art Pt‐single‐atom catalysts. The hollow sphere structure and PtCu alloying increase the number and reactivity of active sites. Density function calculations and electrochemical experiments reveal that the synergy between WO3 and Pt is also responsible for the high HER activity where the hydrogen spillover effect triggers the Volmer–Heyrovsky mechanism and promotes the rapid removal of H* from Pt to re‐expose the active sites. [ABSTRACT FROM AUTHOR]

The role of liver kinase B1 (LKB1) in glioblastoma (GBM) development remains poorly understood. LKB1 may regulate GBM cell metabolism and has been suggested to promote glioma invasiveness. After analyzing LKB1 expression in GBM patient mRNA databases and in tumor tissue via multiparametric immunohistochemistry, we observed that LKB1 was localized and enriched in GBM tumor cells that co‐expressed SOX2 and NESTIN stemness markers. Thus, LKB1‐specific immunohistochemistry can potentially reveal subpopulations of stem‐like cells, advancing GBM patient molecular pathology. We further analyzed the functions of LKB1 in patient‐derived GBM cultures under defined serum‐free conditions. Silencing of endogenous LKB1 impaired 3D‐gliomasphere frequency and promoted GBM cell invasion in vitro and in the zebrafish collagenous tail after extravasation of circulating GBM cells. Moreover, loss of LKB1 function revealed mitochondrial dysfunction resulting in decreased ATP levels. Treatment with the clinically used drug metformin impaired 3D‐gliomasphere formation and enhanced cytotoxicity induced by temozolomide, the primary chemotherapeutic drug against GBM. The IC50 of temozolomide in the GBM cultures was significantly decreased in the presence of metformin. This combinatorial effect was further enhanced after LKB1 silencing, which at least partially, was due to increased apoptosis. The expression of genes involved in the maintenance of tumor stemness, such as growth factors and their receptors, including members of the platelet‐derived growth factor (PDGF) family, was suppressed after LKB1 silencing. The defect in gliomasphere growth caused by LKB1 silencing was bypassed after supplementing the cells with exogenous PFDGF‐BB. Our data support the parallel roles of LKB1 in maintaining mitochondrial homeostasis, 3D‐gliomasphere survival, and hindering migration in GBM. Thus, the natural loss of, or pharmacological interference with LKB1 function, may be associated with benefits in patient survival but could result in tumor spread. [ABSTRACT FROM AUTHOR]

Heat waves generally hit the Sichuan Basin (SCB) in summer, especially in July and August. This study investigates the interannual variability of mid‐summer heat wave frequency (HWF) over the SCB. The leading mode of the SCB mid‐summer HWF, which explains 48% of the total variance, exhibits an uniform spatial pattern and an increasing trend. This leading pattern mainly dominated by two factors: the mid‐to‐upper‐level height anomalies over western Europe and tropical convection anomalies. On one hand, the mid‐level height anomalies over western Europe could affect the HWF over most parts of the SCB by inducing an eastward‐propagating atmospheric teleconnection wave train to northeastern Asia, which causes a northwestward shifted western North Pacific subtropical high, leading to significant subsidence anomalies over the SCB, hence induces less cloudiness and below‐normal precipitation in‐situ. Consequently, there are increased surface solar radiation and decreased soil moisture over the region, favouring the occurrence of HWs there. On the other hand, the enhanced Philippine Sea convection and suppressed tropical eastern Indian Ocean convection excite an anomalous lower‐tropospheric cyclone dominant over the western North Pacific and southern China, which could weaken the transport of water vapour from the tropic oceans to the northeastern SCB and then contributes to decreased precipitation, favouring a higher HWF. [ABSTRACT FROM AUTHOR]

Platelets can secrete multiple growth factors for peripheral nerve repair. However, topically injected platelets are rapidly activated followed by burst release of the cargos, causing limited therapeutic efficiency in vivo. Herein, a platelet‐incorporated hydrogel conduit is shown that acts as a biosynthetic nerve conduit for peripheral nerve repair. This conduit is prepared by rapid 3D printing of the live platelets mixed with bio‐ink containing gelatin methacrylate (GelMA) and poly(ethyleneglycol)diacrylate (PEGDA). The hydrogel can significantly prolong the survival of the incorporated platelets. While the conduit provides a physical foundation for bridging the nerve gaps, live platelets in the conduit sustained‐release multiple growth factors to promote the nerve repair. The in vivo therapeutic efficiency of this platelet‐incorporated nerve conduit is tested in bridging a 10 mm gap in sciatic nerves. The results of morphological, electrophysiological, and histological assessments indicate that the incorporated platelets can significantly promote the hydrogel conduits in peripheral nerve repair. The demonstrated 3D bioprinted nerve conduit with live platelets may show potential clinical application in peripheral nerve repair. [ABSTRACT FROM AUTHOR]

Schizopygopsis stoliczkai (Cyprinidae, subfamily Schizothoracinae) is one of the major freshwater fishes endemic to the northwestern margin of the Tibetan Plateau. In the current study, we used mitochondrial DNA markers cytochrome b (Cyt b) and 16S rRNA (16S), as well as the nuclear marker, the second intron of the nuclear beta-actin gene (Act2), to uncover the phylogeography of S. stoliczkai. In total, we obtained 74 haplotypes from 403 mitochondrial concatenated sequences. The mt DNA markers depict the phylogenetic structures of S. stoliczkai, which consist of clade North and clade South. The split time of the two clades is dated back to 4.27 Mya (95% HPD = 1.96-8.20 Mya). The estimated split time is earlier than the beginning of the ice age of Pleistocene (2.60 Mya), suggesting that the northwestern area of the Tibetan Plateau probably contain at least two glacial refugia for S. stoliczkai. SAMOVA supports the formation of four groups: (i) the Karakash River group; (ii) The Lake Pangong group; (iii) the Shiquan River group; (iv) the Southern Basin group. Clade North included Karakash River, Lake Pangong, and Shiquan River groups, while seven populations of clade South share the haplotypes. Genetic diversity, star-like network, BSP analysis, as well as negative neutrality tests indicate recent expansions events of S. stoliczkai. Conclusively, our results illustrate the phylogeography of S. stoliczkai, implying the Shiquan River is presumably the main refuge for S. stoliczkai. [ABSTRACT FROM AUTHOR]

Magnetic Pd-Ni bimetals with various compositions were synthesized by a one-pot reaction, in which chain-like Pd-Ni bimetals formed through the self-assembly of Pd-Ni nanoparticles. The self-assembly behaviour of the Pd-Ni bimetals gradually changes with the changes in composition. The Pd-Ni nanoparticles form simple chains at lower Pd content, while the Pd-Ni bimetals take on a beads-on-string structure composed of sphere-shaped Pd-Ni-nanoparticle assemblies at higher Pd content. Magnetic hysteresis loops show that Ni-rich assemblies have a higher saturation magnetization than Pd-rich assemblies. The formation mechanism for these Pd-Ni assemblies is proposed, in which the self-assembly behaviours are controlled by the competition of the surfactant interaction and the magnetic dipole interaction. The catalytic activity and selectivity of the hydrogenation of acetophenone over these Pd-Ni bimetals depend on their compositions. [ABSTRACT FROM AUTHOR]