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The current work examined why collectivists engage in more chronic social tuning: to seek harmony or to avoid rejection. In Study 1, 159 Asian participants self-reported being more motivated to avoid rejection in a situation involving social tuning. In Study 2, 190 Asian participants engaged in social tuning to a classmate's perceived views more when primed to avoid rejection than seek harmony. While study 3 found that 192 American participants reported avoiding rejection in social tuning situations, Study 4, showed that 206 American participants did not engage in social tuning when primed to avoid rejection. Collectivists will social tune and reduce prejudice when motivated to avoid rejection. This warrants future attention to cultural variation in other social tuning domains. [ABSTRACT FROM AUTHOR]

In the process of blisk polishing, path planning is a crucial approach to ensure machining efficiency and enhance polishing accuracy. However, existing path generation software does not take into account the large elastic deformation of the polishing tool and cannot guarantee consistent residual error after the processing path. To address these problems, a special effective methodology is proposed for developing an abrasive belt flap wheel (ABFW) polishing path, enhancing the polishing quality of the blisk. To this end, we first establish a motion envelope surface of the ABFW. Then, based on the radial material removal depth model of the ABFW, the amount of material removal is obtained at each contact point. Additionally, the maximum error minimization method is employed to iteratively optimize the solution, obtaining the polishing path for constant residual error. In the experiments, we find that compared to the polishing path generated by commercial software, the optimized polishing path is capable of achieving lower surface residual error and better surface quality. [ABSTRACT FROM AUTHOR]

Regulation of translation is a crucial step in gene expression. Developmental signals and environmental stimuli dynamically regulate translation via upstream small open reading frames (uORFs) and ribosome pausing. Recent studies have revealed many plant genes that are specifically regulated by uORF translation following changes in growth conditions, but ribosome-pausing events are less well understood. In this study, we performed ribosome profiling (Ribo-seq) of etiolated maize (Zea mays) seedlings exposed to light for different durations, revealing hundreds of genes specifically regulated at the translation level during the early period of light exposure. We identified over 400 ribosome-pausing events in the dark that were rapidly released after illumination. These results suggested that ribosome pausing negatively regulates translation from specific genes, a conclusion that was supported by a non-targeted proteomics analysis. Importantly, we identified a conserved nucleotide motif downstream of the pausing sites. Our results elucidate the role of ribosome pausing in the control of gene expression in plants; the identification of the cis-element at the pausing sites provides insight into the mechanisms behind translation regulation and potential targets for artificial control of plant translation. [ABSTRACT FROM AUTHOR]

Harnessing solar energy by photocatalytically converting oxygen and water into high-value-added H2O2 is a promising way of alleviating both environmental and energy issues. It is worth noting that suppressing detrimental side reactions, such as the generation of •O2−, is a critical approach to enhancing H2O2 production. Herein, a 2-fold interpenetrating 3D uranium-organic framework (YTU-W-1) was developed and introduced for photocatalytic H2O2 production. The material demonstrates a different photocatalytic mechanism when employing uranyl as an initiator, as compared with the conventional semiconductor photocatalytic pathway involving photo-generated charge carriers. Benefiting from the strong hydrogen abstraction effect of the U≡O• and the direct one-step oxygen reduction pathway, YTU-W-1 exhibits enhanced photocatalytic performance for H2O2 production with yield efficiency of 221 µmol h−1 g−1. Furthermore, YTU-W-1 displays a high H2O2 selectivity of 68%, confirmed by rotating ring-disk electrode (RRDE) measurement. DFT calculations were used to elucidate the critical role of uranyl in the photocatalytic oxygen reduction reaction for H2O2 production. This research introduces an innovative approach to photo driven H2O2 production, underscoring the potential for heterogeneous catalysts to engage in photocatalytic reactions independently of photo-generated charge carriers. [ABSTRACT FROM AUTHOR]

Osteoporosis is a metabolic bone disease that involves gradual loss of bone density and mass, thus resulting in increased fragility and risk of fracture. Inflammatory cytokines, such as tumour necrosis factor α (TNF‐α), inhibit osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), and several microRNAs are implicated in osteoporosis development. This study aimed to explore the correlation between TNF‐α treatment and miR‐27a‐3p expression in BMSC osteogenesis and further understand their roles in osteoporosis. An osteoporosis animal model was established using ovariectomized (OVX) mice. Compared with Sham mice, the OVX mice had a significantly elevated level of serum TNF‐α and decreased level of bone miR‐27a‐3p, and in vitro TNF‐α treatment inhibited miR‐27a‐3p expression in BMSCs. In addition, miR‐27a‐3p promoted osteogenic differentiation of mouse BMSCs in vitro, as evidenced by alkaline phosphatase staining and Alizarin Red‐S staining, as well as enhanced expression of the osteogenic markers Runx2 and Osterix. Subsequent bioinformatics analysis combined with experimental validation identified secreted frizzled‐related protein 1 (Sfrp1) as a downstream target of miR‐27a‐3p. Sfrp1 overexpression significantly inhibited the osteogenic differentiation of BMSCs in vitro and additional TNF‐α treatment augmented this inhibition. Moreover, Sfrp1 overexpression abrogated the promotive effect of miR‐27a‐3p on the osteogenic differentiation of BMSCs. Furthermore, the miR‐27a‐3p–Sfrp1 axis was found to exert its regulatory function in BMSC osteogenic differentiation via regulating Wnt3a–β‐catenin signalling. In summary, this study revealed that TNF‐α regulated a novel miR‐27a‐3p–Sfrp1 axis in osteogenic differentiation of BMSCs. The data provide new insights into the development of novel therapeutic strategies for osteoporosis. What is the central question of this study?What is the mechanism by which TNF‐α plays its critical role in osteogenesis via the modulation of bone loss and formation?What is the main finding and its importance?TNF‐α regulates a novel miR‐27a‐3p–Sfrp1 axis in osteogenic differentiation of bone marrow mesenchymal stem cells. [ABSTRACT FROM AUTHOR]

The development of adsorbent materials for effective capture of radioactive iodomethane (CH3I) from the off-gas of used nuclear fuel reprocessing, remains a significant and challenging line of research because currently state-of-art adsorbents still suffer from low binding affinity with CH3I. Here, we proposed a brand-new adsorption topological structure by developing a 2D interdigitated layered framework, named SCU-20, featuring slide-like channel with multiple active sites for CH3I capture. The responsive rotating-adaptive aperture of SCU-20 enables the optimal utilization of all active sites within the pore for highly selective recognition and capture of CH3I. A record-breaking CH3I uptake capacity of 1.84 g/g was achieved under static sorption conditions with saturated CH3I vapor. Both experimental and theoretical findings demonstrated that the exceptional uptake of SCU-20 towards CH3I can be attributed to the confined physical electrostatic adsorption of F sites, coupled with the chemical nitrogen methylation reaction with uncoordinated N atoms of pyrazine. Moreover, dynamic CH3I uptake capacity potentially allows for the capture of CH3I in simulated real-world off gas reprocessing conditions. This study highlights the potential of SCU-20 as a promising candidate for efficient capture of iodine species and contributes to the development of effective solutions for radioactive iodine remediation. [ABSTRACT FROM AUTHOR]

The density of rockfill material is an important index to evaluate the quality of rockfill dams. It is of great significance to accurately obtain the densities and permeability coefficients of rockfill material dams quickly and accurately by scientific means. However, it takes a long time to measure the permeability coefficient of rockfill material in practice, which means that such measurements cannot fully reflect all the relevant properties. In this paper, using a convolutional neural network (CNN), a machine learning model was established to predict the permeability coefficient of rockfill material with the full scale (d10~d100), pore ratio, Cu, and Cc as the inputs and the permeability coefficient as the output. Through collecting the permeability coefficient and related data in the literature, the set samples were sorted for model training. The prediction results of the trained CNN model are compared with those of the back propagation (BP) model to verify the accuracy of the CNN model. Laboratory constant head penetration experiments were designed to verify the generalization performance of the model. The results show that compared with the BP model, the CNN model has better applicability to the prediction of the permeability coefficient of rockfill material and that the CNN can obtain better accuracy and meet the requirements of the rough estimation of rockfill materials' permeability in engineering. [ABSTRACT FROM AUTHOR]

The demand for titanium alloy has been increasing in various industries, including aerospace, marine, and biomedical fields, as they fulfilled the need for lightweight, high-strength, and corrosion-resistant material for modern manufacturing. However, titanium alloy has relatively low hardness, poor wear performance, and fatigue properties, which limits its popularization and application. These disadvantages could be efficiently overcome by surface strengthening technology, such as the ultrasonic surface rolling process (USRP). In this study, the true thermo-mechanical deformation behavior of Ti-6Al-4V was obtained by dynamic mechanical experiment using a Hopkinson pressure bar. Moreover, USRP was applied on the Ti-6Al-4V workpiece with different parameters of static forces to investigate the evolution in surface morphology, surface roughness, microstructure, hardness, residual stress, and fatigue performance. The strain rate and temperature during the USRP of Ti-6Al-4V under the corresponding conditions were about 3000 s−1 and 200 °C, respectively, which were derived from the numerical simulation. The correlation between the true thermo-mechanical behavior of Ti-6Al-4V alloy and the USRP parameters of the Ti-6Al-4V workpiece was established, which could provide a theoretical contribution to the optimization of the USRP parameters. After USRP, the cross-sectional hardness distribution of the workpiece was shown to initially rise, followed by a subsequent decrease, ultimately to matrix hardness. The cross-sectional residual compressive stress distribution of the workpiece showed a tendency to initially reduce, then increase, and finally decrease to zero. The fatigue performance of the workpiece was greatly enhanced after USRP due to the effect of grain refinement, work hardening, and beneficial residual compressive stress, thereby inhibiting the propagation of the fatigue crack. However, it could be noted that the excessive static force parameter of USRP could induce the decline in surface finish and compressive residual stress of the workpiece, which eliminated the beneficial effect of the USRP treatment. This indicated that the choice of the optimal USRP parameters was highly crucial. This work would be conducive to achieving high-efficiency and low-damage USRP machining, which could be used to effectively guide the development of high-end equipment manufacturing. [ABSTRACT FROM AUTHOR]

Lysine‐specific demethylase 1 (LSD1) is a flavin adenine dinucleotide (FAD) dependent monoamine oxidase (MAO) that erases the mono‐, and dimethylation of histone 3 lysine 4 (H3K4), resulting in the suppression of target gene transcriptions. Besides, it can also demethylate some nonhistone substrates to regulate their biological functions. As reported, LSD1 is widely upregulated and plays a key role in several kinds of cancers, pharmacological or genetic ablation of LSD1 in cancer cells suppresses cell aggressiveness by several distinct mechanisms. Therefore, numerous LSD1 inhibitors, including covalent and noncovalent, have been developed and several of them have entered clinical trials. Herein, we systemically reviewed and discussed the biological function of LSD1 in tumors, lymphocytes as well as LSD1‐targeting inhibitors in clinical trials, hoping to benefit the field of LSD1 and its inhibitors. [ABSTRACT FROM AUTHOR]

Decreasing the power consumption of light‐emitting diodes (LEDs) and increasing the energy generation of solar cells are crucial tasks toward the mitigation of greenhouse gas emissions and Paris Agreement goals. Lead (Pb)‐free halide double perovskites, identified as environmentally friendly alternatives to Pb‐based perovskites, are not deemed useful thus far due to the absence of high photoluminescence quantum yield (PLQY) examples and large bandgaps. Herein, penta‐cationic antimony (Sb5+)‐doping strategy is demonstrated for the benchmark material of Cs2NaInCl6, achieving blue emission with near‐unity PLQY and the lowest bandgap of 1.24 eV. The excellent PLQY observed in the material is attributed to Sb5+ doping‐induced Jahn–Teller distortion in Cs2NaInCl6 and a newly emerged band structure, which has remained undisclosed in all previous reports. This groundbreaking discovery represents the first instance in the field of perovskite materials where the incorporation of a single dopant has resulted in a zero‐to‐one enhancement in their emission profile. This breakthrough is expected to have profound implications for advancing research in the utilization of similar dopants, such as manganese cations (Mn6+ and Mn7+), not only in halide perovskite structures but also in oxide‐based perovskites and other semiconductor systems. [ABSTRACT FROM AUTHOR]

Background: Atrial cardiopathy is a proposed mechanism of embolic stroke of undetermined source (ESUS). Left atrial (LA) strain may identify early atrial cardiopathy prior to structural changes. We aim to study the associations between LA strain, ESUS, and atrial fibrillation (AF) detection in ESUS. Methods: The study population included patients with ESUS and noncardioembolic (NCE) stroke presenting to the Rhode Island Hospital Stroke Center between January 2016 and June 2017 who underwent transthoracic echocardiography. Speckle tracking echocardiography (STE) was used to measure the three phases of LA strain (reservoir, conduit, and contractile). Binary logistic regression analysis was performed to determine the associations between LA strain and stroke subtype (ESUS vs. NCE) as well as follow‐up detection of AF in ESUS patients. Results: We identified 656 patients, 307 with ESUS and 349 with NCE. In binary logistic regression, the lowest tertiles of LA reservoir (adjusted OR 1.944, 95% CI 1.266–2.986, p =.002), contractile (aOR 1.568, 95% CI 1.035–2.374, p =.034), and conduit strain (aOR 2.288, 95% CI 1.448–3.613, p =.001) were more likely to be significantly associated with ESUS compared to NCE stroke. Among all ESUS patients, the lowest tertiles of LA reservoir strain (OR 2.534, 95% CI 1.029–6.236, p =.043), contractile strain (OR 2.828, 95% CI 1.158–6.903, p =.022), and conduit strain (OR 2.614, 95% CI 1.003–6.815, p =.049) were significantly associated with subsequent detection of AF. Conclusion: Reduced LA strain is associated with ESUS occurrence and AF detection in ESUS patients. Therefore, quantification of LA strain in ESUS patients may improve risk stratification and guide secondary prevention strategies. [ABSTRACT FROM AUTHOR]

Ferroptosis featured by iron‐dependent lipid peroxidation plays a critical role in tumor regression, offering an alternative therapeutic target for the treatment of aggressive triple‐negative breast cancer. However, the traditional delivery strategy to enrich iron deposition is limited in producing a surplus of lipid oxidation because of the aggressive antioxidant response established in solid tumors. Here, vitamin B2‐ferric chloride nanocomplex self‐assembled through the coordination of ferric iron and hydroxy groups to simultaneously promote iron accumulation and oxidative stress is employed. It is observed that the self‐assembly nanostructures with appropriate size enable effective delivery of the therapeutic agents to the tumor site and cancer cells. More importantly, sonosensitizer vitamin B2 and ferric chloride cooperatively facilitate the production of reactive oxygen species and amplify nanocatalytic therapy. To further disrupt the antioxidant system, metformin with solute carrier family 7 member 11 inhibitory activity is used to synergistically boost ferroptosis of tumor cells. The combinational ferroptosis promoter exhibits augmented nanocatalytic antitumor efficacy in 4T1 tumor‐bearing mice with negligible adverse effects. Taken together, this study may provide a novel paradigm of self‐assembled vitamin B2‐ferric nanocomplex for ferroptosis regulation. [ABSTRACT FROM AUTHOR]

Spinal instrumented rod migrating from the surgical site to another remote site in the body is rare. Some cases result in organ or blood vessel injury. Most reported cases were asymptomatic until the finally injuries were generated. We report a unique case of spinal implant failure in which the rod moved from lumbar spine into chest 13 years post lumbar instrumentation. The migrated rod caused no damage to the organs in the pleural cavity but did cause an atypical pleural irritation syndrome which seemed to correlate with the mechanical irritation caused by the rod. These atypical symptoms of rod migration have not been reported previously. [ABSTRACT FROM AUTHOR]

Precise prediction of milling force is a crucial issue in multi-axis milling, which is important for evaluating the tool life and surface quality. In this paper, an improved force model for ball-end milling is proposed based on a novel uncut chip thickness (UCT) model as well as the consideration of edge effect and size effect. The computational model of UCT takes into account the influence of lead and tilt angles in ball-end milling. In addition, it utilizes a new discretization method of the uncut chip area that ensures the local cutting edge is perpendicular to the length of the elemental uncut chip area, making it more compatible with the classical oblique cutting model. For each elemental cutting edge, the force components are calculated through a purely analytical approach, considering the shear force, edge force, and size effect caused by cutting edge geometry in milling process. The proposed model is comprehensively validated with both FEM and multi-axis milling experiments for aluminum and titanium. The results indicate that the proposed model can predict the dynamic milling force under various cutting conditions in a good manner. Moreover, considering edge and size effects can further improve the prediction accuracy. [ABSTRACT FROM AUTHOR]

The development of high‐performance X‐ray detectors requires scintillators with fast decay time, high light yield, stability, and X‐ray absorption capacity, which are difficult to achieve in a single material. Here, we present the first example of a lanthanide chalcogenide of LaCsSiS4 : 1 % Ce3+ that simultaneously integrates multiple desirable properties for an ideal scintillator. LaCsSiS4 : 1 % Ce3+ demonstrates a remarkably low detection limit of 43.13 nGyair s−1 and a high photoluminescence quantum yield of 98.24 %, resulting in a high light yield of 50480±1441 photons/MeV. Notably, LaCsSiS4 : 1 % Ce3+ exhibits a fast decay time of only 29.35±0.16 ns, making it one of the fastest scintillators among all lanthanide‐based inorganic scintillators. Furthermore, this material shows robust radiation and moisture resistance, endowing it with suitability for chemical processing under solution conditions. To demonstrate the X‐ray imaging capacity of LaCsSiS4 : 1 % Ce3+, we fabricated a flexible X‐ray detector that achieved a high spatial resolution of 8.2 lp mm−1. This work highlights the potential of lanthanide chalcogenide as a promising candidate for high‐performance scintillators. [ABSTRACT FROM AUTHOR]

The development of high‐performance X‐ray detectors requires scintillators with fast decay time, high light yield, stability, and X‐ray absorption capacity, which are difficult to achieve in a single material. Here, we present the first example of a lanthanide chalcogenide of LaCsSiS4 : 1 % Ce3+ that simultaneously integrates multiple desirable properties for an ideal scintillator. LaCsSiS4 : 1 % Ce3+ demonstrates a remarkably low detection limit of 43.13 nGyair s−1 and a high photoluminescence quantum yield of 98.24 %, resulting in a high light yield of 50480±1441 photons/MeV. Notably, LaCsSiS4 : 1 % Ce3+ exhibits a fast decay time of only 29.35±0.16 ns, making it one of the fastest scintillators among all lanthanide‐based inorganic scintillators. Furthermore, this material shows robust radiation and moisture resistance, endowing it with suitability for chemical processing under solution conditions. To demonstrate the X‐ray imaging capacity of LaCsSiS4 : 1 % Ce3+, we fabricated a flexible X‐ray detector that achieved a high spatial resolution of 8.2 lp mm−1. This work highlights the potential of lanthanide chalcogenide as a promising candidate for high‐performance scintillators. [ABSTRACT FROM AUTHOR]

This paper presents an investigation into the parasitic capacitance of an RF contact scheme for lumped-element EAMs. Test structures are fabricated to analyse this parasitic capacitance via S 11 characterisation using a vector network analyser (VNA). Optimisations of the contact scheme lead to the parasitic capacitance being reduced to <10 fF. EAMs using this contact scheme are fabricated and characterised using S 11 measurements. These S 11 measurements are used to simulate S 21 measurements, which predict a f3dB bandwidth of near 80 GHz using an equivalent circuit model. [ABSTRACT FROM AUTHOR]

Skin epidermis constitutes the outer permeability barrier that protects the body from dehydration, heat loss, and myriad external assaults. Mechanisms that maintain barrier integrity in constantly challenged adult skin and how epidermal dysregulation shapes the local immune microenvironment and whole‐body metabolism remain poorly understood. Here, we demonstrate that inducible and simultaneous ablation of transcription factor‐encoding Ovol1 and Ovol2 in adult epidermis results in barrier dysregulation through impacting epithelial‐mesenchymal plasticity and inflammatory gene expression. We find that aberrant skin immune activation then ensues, featuring Langerhans cell mobilization and T cell responses, and leading to elevated levels of secreted inflammatory factors in circulation. Finally, we identify failure to gain body weight and accumulate body fat as long‐term consequences of epidermal‐specific Ovol1/2 loss and show that these global metabolic changes along with the skin barrier/immune defects are partially rescued by immunosuppressant dexamethasone. Collectively, our study reveals key regulators of adult barrier maintenance and suggests a causal connection between epidermal dysregulation and whole‐body metabolism that is in part mediated through aberrant immune activation. Synopsis: Skin epidermal‐specific loss of Ovol1 and Ovol2 transcription factors also causes local immune activation and whole‐body metabolic changes. These defects are partially rescued by administration of the immunosuppressant dexamethasone. EMT‐suppressing transcription factors Ovol1 and Ovol2 are required for epidermal barrier maintenance in adult skin.Ovol1/2 loss‐induced epidermal dysregulation elicits aberrant immune activation and increased production of inflammatory factors.Ovol1/2 perturbation in epidermis results in a failure to gain body weight and accumulate body fat.Partial rescue by dexamethasone implicates connections among epidermal and immune homeostasis, and global metabolism. [ABSTRACT FROM AUTHOR]

D‐1553 is a small molecule inhibitor selectively targeting KRASG12C and currently in phase II clinical trials. Here, we report the preclinical data demonstrating antitumor activity of D‐1553. Potency and specificity of D‐1553 in inhibiting GDP‐bound KRASG12C mutation were determined by thermal shift assay and KRASG12C‐coupled nucleotide exchange assay. In vitro and in vivo antitumor activity of D‐1553 alone or in combination with other therapies were evaluated in KRASG12C mutated cancer cells and xenograft models. D‐1553 showed selective and potent activity against mutated GDP‐bound KRASG12C protein. D‐1553 selectively inhibited ERK phosphorylation in NCI‐H358 cells harboring KRASG12C mutation. Compared to the KRAS WT and KRASG12D cell lines, D‐1553 selectively inhibited cell viability in multiple KRASG12C cell lines, and the potency was slightly superior to sotorasib and adagrasib. In a panel of xenograft tumor models, D‐1553, given orally, showed partial or complete tumor regression. The combination of D‐1553 with chemotherapy, MEK inhibitor, or SHP2 inhibitor showed stronger potency on tumor growth inhibition or regression compared to D‐1553 alone. These findings support the clinical evaluation of D‐1553 as an efficacious drug candidate, both as a single agent or in combination, for patients with solid tumors harboring KRASG12C mutation. [ABSTRACT FROM AUTHOR]

The bacteria pathogen Xanthomonas oryzae pv. oryzae (Xoo) infects rice and causes the severe disease of rice bacteria blight. As the central regulator of the salic acid (SA) signaling pathway, NPR1 is responsible for sensing SA and inducing the expression of pathogen-related (PR) genes in plants. Overexpression of OsNPR1 significantly increases rice resistance to Xoo. Although some downstream rice genes were found to be regulated by OsNPR1, how OsNPR1 affects the interaction of rice-Xoo and alters Xoo gene expression remains unknown. In this study, we challenged the wild-type and OsNPR1-OE rice materials with Xoo and performed dual RNA-seq analyses for the rice and Xoo genomes simultaneously. In Xoo-infected OsNPR1-OE plants, rice genes involved in cell wall biosynthesis and SA signaling pathways, as well as PR genes and nucleotide-binding site-leucine-rich repeat (NBS-LRR) genes, were significantly upregulated compared to rice variety TP309. On the other hand, Xoo genes involved in energy metabolism, oxidative phosphorylation, biosynthesis of primary and secondary metabolism, and transportation were repressed. Many virulence genes of Xoo, including genes encoding components of type III and other secretion systems, were downregulated by OsNPR1 overexpression. Our results suggest that OsNPR1 enhances rice resistance to Xoo by bidirectionally regulating gene expression in rice and Xoo. [ABSTRACT FROM AUTHOR]

The noninflamed microenvironment in prostate cancer represents a barrier to immunotherapy. Genetic alterations underlying cancer cell–intrinsic oncogenic signaling are increasingly appreciated for their role in shaping the immune landscape. Recently, we identified Pygopus 2 (PYGO2) as the driver oncogene for the amplicon at 1q21.3 in prostate cancer. Here, using transgenic mouse models of metastatic prostate adenocarcinoma, we found that Pygo2 deletion decelerated tumor progression, diminished metastases, and extended survival. Pygo2 loss augmented the activation and infiltration of cytotoxic T lymphocytes (CTLs) and sensitized tumor cells to T cell killing. Mechanistically, Pygo2 orchestrated a p53/Sp1/Kit/Ido1 signaling network to foster a microenvironment hostile to CTLs. Genetic or pharmacological inhibition of Pygo2 enhanced the antitumor efficacy of immunotherapies using immune checkpoint blockade (ICB), adoptive cell transfer, or agents inhibiting myeloid-derived suppressor cells. In human prostate cancer samples, Pygo2 expression was inversely correlated with the infiltration of CD8+ T cells. Analysis of the ICB clinical data showed association between high PYGO2 level and worse outcome. Together, our results highlight a potential path to improve immunotherapy using Pygo2-targeted therapy for advanced prostate cancer. Breaking down the barrier to prostate cancer immunotherapy: Prostate cancer is minimally responsive to most immunotherapy approaches due to poor tumor infiltration of lymphocytes. Using mouse models of prostate cancer, Zhu et al. found that cancer cell expression of the chromatin effector Pygo2 promotes immunotherapy resistance by restraining tumor T cell infiltration and cytotoxicity. Pygo2's suppressive effects were mediated by promoting expression of the receptor tyrosine kinase Kit and activity of indoleamine 2,3-dioxygenase 1, which occurred independently of Wnt/β-catenin signaling. Genetic deletion or pharmacological inhibition of Pygo2 enhanced prostate tumor responses to a wide range of immunotherapies including adoptive T cell therapy, CXCR2 blockade, and PD-1/CTLA-4 immune checkpoint blockade. Together, these results demonstrate that Pygo2 regulates cancer cell-extrinsic immune features and represents a potential target for reducing prostate cancer resistance to immunotherapy. —CO [ABSTRACT FROM AUTHOR]

Platinum recovery from waste electrical and electronic equipment (WEEE) in highly acidic solutions is significant to the electronics industry and environmental remediation. However, the lack of ingenious design and synergetic coordination gives rise to unsatisfied PtCl42− extraction capacities and selectivities in most previously reported adsorbents (e.g., polymeric and inorganic materials). Herein, we proposed a synergistic strategy that realizes highly selective PtCl42− uptake through first- and second-sphere coordinations. The proof-of-concept imine-linked covalent organic framework (SCU-COF-3) was found to chelate PtCl42−via the direct N⋯Pt coordination and the synergistically interlaminar N—H⋯Cl hydrogen bonds, which was disclosed by the comprehensive analysis of extended X-ray adsorption fine structure (EXAFS) characterizations and density functional theory (DFT) calculations. The unique adsorption mechanism imparts a superior adsorption capacity (168.4 mg g−1) and extraordinary Pt(II) selectivity to SCU-COF-3 under static conditions. In addition, SCU-COF-3 exhibits an upgraded distribution coefficient of 1.62 × 105 mL g−1, one order of magnitude higher than those of reported natural adsorbents. Specifically, SCU-COF-3 can extract PtCl42− quantitatively from a simulated acidic waste solution coexisting with other 12 competitive ions, suggesting its promising application in practical scenarios. [ABSTRACT FROM AUTHOR]

Leveraging metal–organic framework (MOF) to eliminate radioactive contaminants has invariably received much attention, but low preparation efficiency and poor selectivity have still limited its actual application. Herein, it is found that a fourfold interpenetrated cationic MOF (Ag‐TPPE) can be rapidly synthesized by only mixing, stirring, or sonication at room temperature. More impressively, the preparation process can be completed in <1 min. Up to now, this is the first report that cationic MOFs can be obtained by directly mixing the corresponding raw materials at room temperature. In addition to holding the rare merits of structural stability in extremely strong bases (8 m NaOH), Ag‐TPPE can selectively remove TcO4− in the presence of large excess SO42− or NO3−. Based on its ultra‐high selectivity, Ag‐TPPE exhibits exceptional removal rate for TcO4− from simulated Hanford and Savannah River Site waste streams, which refreshes the record of selective sorption of TcO4− at low solid/liquid ratio, overcoming the drawback of overused sorbent in treatment of radioactive waste solution. Such superior sorption capabilities are thoroughly elucidated by the density functional theory calculations on a molecular level, clearly disclosing that TcO4− can enter into the framework through breathing effect and is trapped in the large cavity through dense hydrogen bonds. [ABSTRACT FROM AUTHOR]

Complex surfaces are widely used in aerospace, energy, and national defense industries. As one of the major means of manufacturing such as complex surfaces, the multi-axis numerical control (NC) machining technique makes much contribution. When the size of complex surfaces is large or the machining space is narrow, the multi-axis NC machining may not be a good choice because of its high cost and low dexterity. Robotic machining is a beneficial supplement to the NC machining. Since it has the advantages of large operating space, good dexterity, and easy to realize parallel machining, it is a promising technique to enhance the capability of traditional NC machining. However, whether it is the multi-axis NC machining or the robotic machining, owing to the complex geometric properties and strict machining requirements, high-efficiency and high-accuracy machining of complex surfaces has always been a great challenge and remains a cutting-edge problem in the current manufacturing field. In this paper, by surveying the machining of complex parts and large complex surfaces, the theory and technology of high-efficiency and high-accuracy machining of complex surfaces are reviewed thoroughly. Then, a series of typical applications are introduced to show the state-of-the-art on the machining of complex surfaces, especially the recently developed industrial software and equipment. Finally, the summary and prospect of the machining of complex surfaces are addressed. To the best of our knowledge, this may be the first attempt to systematically review the machining of complex surfaces by the multi-axis NC and robotic machining techniques, in order to promote the further research in related fields. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor, and it is associated with poor prognosis. Its characteristics of being highly invasive and undergoing heterogeneous genetic mutation, as well as the presence of the blood–brain barrier (BBB), have reduced the efficacy of GBM treatment. The emergence of a novel therapeutic method, namely, sonodynamic therapy (SDT), provides a promising strategy for eradicating tumors via activated sonosensitizers coupled with low-intensity ultrasound. SDT can provide tumor killing effects for deep-seated tumors, such as brain tumors. However, conventional sonosensitizers cannot effectively reach the tumor region and kill additional tumor cells, especially brain tumor cells. Efforts should be made to develop a method to help therapeutic agents pass through the BBB and accumulate in brain tumors. With the development of novel multifunctional nanosensitizers and newly emerging combination strategies, the killing ability and selectivity of SDT have greatly improved and are accompanied with fewer side effects. In this review, we systematically summarize the findings of previous studies on SDT for GBM, with a focus on recent developments and promising directions for future research. [ABSTRACT FROM AUTHOR]

Breast cancer is a heterogenous disease that can be classified into multiple subtypes including the most aggressive basal-like and triple-negative subtypes. Understanding the heterogeneity within the normal mammary basal epithelial cells holds the key to inform us about basal-like cancer cell differentiation dynamics as well as potential cells of origin. Although it is known that the mammary basal compartment contains small pools of stem cells that fuel normal tissue morphogenesis and regeneration, a comprehensive yet focused analysis of the transcriptional makeup of the basal cells is lacking. We used single-cell RNA-sequencing and multiplexed RNA in-situ hybridization to characterize mammary basal cell heterogeneity. We used bioinformatic and computational pipelines to characterize the molecular features as well as predict differentiation dynamics and cell–cell communications of the newly identified basal cell states. We used genetic cell labeling to map the in vivo fates of cells in one of these states. We identified four major distinct transcriptional states within the mammary basal cells that exhibit gene expression signatures suggestive of different functional activity and metabolic preference. Our in vivo labeling and ex vivo organoid culture data suggest that one of these states, marked by Egr2 expression, represents a dynamic transcriptional state that all basal cells transit through during pubertal mammary morphogenesis. Our study provides a systematic approach to understanding the molecular heterogeneity of mammary basal cells and identifies previously unknown dynamics of basal cell transcriptional states. [ABSTRACT FROM AUTHOR]

Cutting tools with round edge can enhance the performance of machining difficult-to-machine materials, while the complex contact mechanism related to micro cutting edge limits the deeper understanding of cutting mechanics. Material separation, which is associate to plough mechanism with formation of dead metal zone (DMZ), also requires the analysis of contact behavior. This study develops a contact model along the round edge together with the illustration of DMZ, with three contact feature points defined to explain the contact situation between workpiece and cutting edge. Among these feature points, two separation points related to DMZ classify the sliding and sticking region considering the dual-zone approach. The stagnation point is the zero shear stress point where a sudden change in shear stress direction happens. Besides, the parabolic stress model obtained from finite element simulations is established to define the normal contact distribution along the round edge. In this basis, the tool-based cutting forces are predicted with proposed contact model and two contact force components are classified for different contact regions. The proposed contact feature points and contact stress are validated through illustration with finite element simulations. Besides, orthogonal cutting tests ensure the practicality and accuracy of the proposed contact model and predicted cutting forces. [ABSTRACT FROM AUTHOR]

Stem-cell containing mammary basal epithelial cells exist in a quasi-mesenchymal transcriptional state characterized by simultaneous expression of typical epithelial genes and typical mesenchymal genes. Whether robust maintenance of such a transcriptional state is required for adult basal stem cells to fuel self-renewal and regeneration remains unclear. In this work, we utilized SMA-CreER to direct efficient basal cell-specific deletion of Ovol2, which encodes a transcription factor that inhibits epithelial-to-mesenchymal transition (EMT), in adult mammary gland. We identified a basal cell-intrinsic role of Ovol2 in promoting epithelial, and suppressing mesenchymal, molecular traits. Interestingly, Ovol2-deficient basal cells display minimal perturbations in their ability to support tissue homeostasis, colony formation, and transplant outgrowth. These findings underscore the ability of adult mammary basal cells to tolerate molecular perturbations associated with altered epithelia-mesenchymal plasticity without drastically compromising their self-renewal potential. [ABSTRACT FROM AUTHOR]

Mammary gland is an outstanding system to study the regulatory mechanisms governing adult epithelial stem cell activity. Stem cells in the basal layer of the mammary gland fuel the morphogenesis and regeneration of a complex epithelial network during development and upon transplantation. The self-renewal of basal stem/progenitor cells is subjected to regulation by both cell-intrinsic and extrinsic mechanisms. Nfatc1 is a transcription factor that regulates breast tumorigenesis and metastasis, but its role in mammary epithelial development and stem cell function has not been investigated. Here we show that Nfatc1 is expressed in a small subset of mammary basal epithelial cells and its epithelial-specific deletion results in mild defects in side branching and basal-luminal cell balance. Moreover, Nfatc1-deficient basal cells exhibit reduced colony forming ability in vitro and somewhat compromised regenerative potential upon transplantation. Thus, our study provides evidence for a detectable yet non-essential role of Nfatc1 in mammary epithelial morphogenesis and basal stem/progenitor cell self-renewal. [ABSTRACT FROM AUTHOR]

Keloid is a type of unusually raised scar. Botulinum toxin A (BTX‐A) has a great application potential in keloids treatment. Here, we investigated the functional role of BTX‐A in keloids. We separated keloid tissues and normal skin tissues from keloid patients and found that the expression of myofibroblast markers, α‐SMA, Collagen I, and Collagen III was increased in the keloid tissues as compared with normal skin tissues. Keloid fibroblasts derived from keloid tissues were treated with TGF‐β1 to induce the differentiation of fibroblasts into myofibroblasts. The keloid myofibroblasts displayed a significant up‐regulation of α‐SMA. BTX‐A enhanced the expression of adipocyte markers, PPARγ and C/EBPα, and increased the accumulation of lipid droplets, and reduced the expression of α‐SMA, Collagen I, and Collagen III in the keloid myofibroblasts. Moreover, BTX‐A enhanced the expression of BMP4 and p‐smad1/5/8. Noggin (BMP4 antagonist) treatment reversed BTX‐A‐mediated increase of PPARγ and C/EBPα expression and lipid droplets, and down‐regulation of α‐SMA, Collagen I, and Collagen III in primary keloid myofibroblasts. In conclusion, BTX‐A promoted the transdifferentiation of primary keloid myofibroblasts into adipocyte‐like cells, which may attribute to activate BMP4/Smad signalling pathway. Thus, this study provides new insights into the mechanism of BTX‐A in keloid. [ABSTRACT FROM AUTHOR]

Luminescent covalent organic frameworks (COFs) find promising applications in chemical sensing, photocatalysis, and optoelectronic devices, however, the majority of COFs are non or weakly emissive owing to the aggregation‐caused quenching (ACQ) or the molecular thermal motion‐based energy dissipation. Here, we report a previously unperceived approach to improve luminescence performance of COFs by introducing isotope effect, which is achieved through substitution of hydrogen from high‐frequency oscillators X‐H (X=O, N, C) by heavier isotope deuterium. Combining the "bottom‐up" and in situ deuteration methods generates the first deuterated COF, which exhibits an impressively 19‐fold enhancement in quantum yield over that of the non‐deuterated counterpart. These results are interpreted by theoretical calculations as the consequence of slower C/N‐D and OD⋅⋅⋅O vibrations that impede the nonradiative deactivation process. The proposed strategy is proved applicable to many other types of emissive COFs. [ABSTRACT FROM AUTHOR]

Luminescent covalent organic frameworks (COFs) find promising applications in chemical sensing, photocatalysis, and optoelectronic devices, however, the majority of COFs are non or weakly emissive owing to the aggregation‐caused quenching (ACQ) or the molecular thermal motion‐based energy dissipation. Here, we report a previously unperceived approach to improve luminescence performance of COFs by introducing isotope effect, which is achieved through substitution of hydrogen from high‐frequency oscillators X‐H (X=O, N, C) by heavier isotope deuterium. Combining the "bottom‐up" and in situ deuteration methods generates the first deuterated COF, which exhibits an impressively 19‐fold enhancement in quantum yield over that of the non‐deuterated counterpart. These results are interpreted by theoretical calculations as the consequence of slower C/N‐D and OD⋅⋅⋅O vibrations that impede the nonradiative deactivation process. The proposed strategy is proved applicable to many other types of emissive COFs. [ABSTRACT FROM AUTHOR]

The CCR4‐NOT complex is a major mRNA deadenylase in eukaryotes, comprising the catalytic subunits CNOT6/6L and CNOT7/8, as well as CNOT4, a regulatory subunit with previously undetermined functions. These subunits have been hypothesized to play synergistic biochemical functions during development. Cnot7 knockout male mice have been reported to be infertile. In this study, viable Cnot6/6l double knockout mice are constructed, and the males are fertile. These results indicate that CNOT7 has CNOT6/6L‐independent functions in vivo. It is also demonstrated that CNOT4 is required for post‐implantation embryo development and meiosis progression during spermatogenesis. Conditional knockout of Cnot4 in male germ cells leads to defective DNA damage repair and homologous crossover between X and Y chromosomes. CNOT4 functions as a previously unrecognized mRNA adaptor of CCR4‐NOT by targeting mRNAs to CNOT7 for deadenylation of poly(A) tails, thereby mediating the degradation of a subset of transcripts from the zygotene to pachytene stage. The mRNA removal promoted by the CNOT4‐regulated CCR4‐NOT complex during the zygotene‐to‐pachytene transition is crucial for the appropriate expression of genes involved in the subsequent events of spermatogenesis, normal DNA double‐strand break repair during meiosis, efficient crossover between X and Y chromosomes, and ultimately, male fertility. [ABSTRACT FROM AUTHOR]

The CCR4‐NOT complex is a major mRNA deadenylase in eukaryotes, comprising the catalytic subunits CNOT6/6L and CNOT7/8, as well as CNOT4, a regulatory subunit with previously undetermined functions. These subunits have been hypothesized to play synergistic biochemical functions during development. Cnot7 knockout male mice have been reported to be infertile. In this study, viable Cnot6/6l double knockout mice are constructed, and the males are fertile. These results indicate that CNOT7 has CNOT6/6L‐independent functions in vivo. It is also demonstrated that CNOT4 is required for post‐implantation embryo development and meiosis progression during spermatogenesis. Conditional knockout of Cnot4 in male germ cells leads to defective DNA damage repair and homologous crossover between X and Y chromosomes. CNOT4 functions as a previously unrecognized mRNA adaptor of CCR4‐NOT by targeting mRNAs to CNOT7 for deadenylation of poly(A) tails, thereby mediating the degradation of a subset of transcripts from the zygotene to pachytene stage. The mRNA removal promoted by the CNOT4‐regulated CCR4‐NOT complex during the zygotene‐to‐pachytene transition is crucial for the appropriate expression of genes involved in the subsequent events of spermatogenesis, normal DNA double‐strand break repair during meiosis, efficient crossover between X and Y chromosomes, and ultimately, male fertility. [ABSTRACT FROM AUTHOR]

As one of most problematic radionuclides, technetium‐99, mainly in the form of anionic pertechnetate (TcO4−), exhibits high environmental mobility, long half‐life, and radioactive hazard. Due to low charge density and high hydrophobicity for this tetrahedral anion, it is extremely difficult to recognize it in water. Seeking efficient and selective recognition method for TcO4− is still a big challenge. Herein, a new water‐stable cationic metal‐organic framework (ZJU‐X8) was reported, bearing tetraphenylethylene pyrimidine‐based aggregation‐induced emission (AIE) ligands and attainable silver sites for TcO4− detection. ZJU‐X8 underwent an obvious spectroscopic change from brilliant blue to flavovirens and exhibited splendid selectivity towards TcO4−. This uncommon fluorescent recognition mechanism was well elucidated by batch sorption experiments and DFT calculations. It was found that only TcO4− could enter into the body of ZJU‐X8 through anion exchange whereas other competing anions were excluded outside. Subsequently, after interaction between TcO4− and silver ions, the electron polarizations from pyrimidine rings to Ag+ cations significantly lowered the energy level of the π* orbital and thus reduced the π–π* energy gap, resulting in a red‐shift in the fluorescent spectra. [ABSTRACT FROM AUTHOR]

Our previous study found that Fengbaisan improved chronic obstructive pulmonary diseases (COPD). To elucidate the mechanism of Fengbaisan in COPD. Rats in Model, FBS, FBS + DMSO and FBS + EX527 groups received cigarette smoke extract (CSE) inhalation and intratracheal instillation of lipopolysaccharide to establish COPD model. Normal group received room air and normal saline. The COPD rats were given Fengbaisan (1 mL/d) or combined with EX527 (5 mg/kg/2 d) by intraperitoneal injection. Human lung carcinoma (A549) cells were treated with 10% CSE, 10% serum-containing Fengbaisan or EX527. We observed lung percentage of forced expiratory volume in first 0.3 sec to forced vital capacity (FEV0.3/FVC), inspiratory resistance (RI) and lung dynamic compliance (Cdyn) of rats. The lung pathological changes, the number of inflammatory cells and neutrophils, inflammatory factor, apoptosis, gene and protein expression were examined. SIRT1 was downregulated in lung tissues of COPD rats and CSE-induced A549 cells. Fengbaisan enhanced FEV0.3/FVC (74.28%) and Cdyn (0.28 cm H2O/mL/s), and reduced RI (0.48 mL/cm H2O) of COPD rats. Moreover, Fengbaisan promoted SIRT1 expression, and repressed TIMP-1/MMP-9 expression. Fengbaisan enhanced apoptosis and the expression of GRP78, caspase-12 and caspase-3. The inflammatory factor levels, the number of inflammatory cells and neutrophils, and lung lesions were inhibited by Fengbaisan in COPD rats. The influence conferred by Fengbaisan was abolished by EX527. Fengbaisan inhibits endoplasmic reticulum stress and inflammation reaction by up-regulating SIRT1 expression to improve COPD. Therefore, Fengbaisan may be an effective Chinese medicine for treating COPD. [ABSTRACT FROM AUTHOR]

Er Miao San (EMS) is a traditional Chinese medicine composed of Atractylodis Rhizoma and Phellodendri Cortex in a 1:1 weight ratio. EMS has been used to treat rheumatism in China for many years. To evaluate the anti-arthritic activity of EMS extract on adjuvant-induced arthritis (AA) in Sprague-Dawley rats and to clarify its mechanisms of action. EMS (0.75, 1.5 and 3 g/kg, once daily) was orally administered from day 18 after immunization to day 31. The effects of EMS on AA rats were evaluated by histopathological examination, paw swelling and polyarthritis index. The proliferation of fibroblast-like synoviocyte (FLS) and T cells was detected by CCK-8. The percentages of Th17 cells and Treg cells in splenocytes were determined by flow cytometry. Levels of cytokines in serum were detected by ELISA. EMS treatment significantly decreased the paw volume (from 1.20 to 0.81), polyarthritis index (from 9.56 to 4.46) and alleviated ankle joint histopathology in AA rats. EMS inhibited the proliferation of FLS and T cells. Furthermore, EMS treatment decreased Th17 cells (from 4.62 to 2.08%) and increased Treg cells (from 2.77 to 4.75%) in splenocytes. The levels of IL-17A, TNF-α and IL-6 were remarkably decreased in the serum of EMS-treated rats, whereas the levels of IL-10 and TGF-β1 were significantly increased. EMS exhibits anti-arthritic activity in the AA model by regulating the balance of cytokines and the ratio of Th17 and Treg cells. These insights may provide an experimental basis for the clinical treatment of RA. [ABSTRACT FROM AUTHOR]

Radio‐photoluminescence (RPL) materials display a distinct radiation‐induced permanent luminescence center, and therefore find application in the detection of ionizing radiation. The current inventory of RPL materials, which were discovered by serendipity, has been limited to a small number of metal‐ion‐doped inorganic materials. Here we document the RPL of a metal–organic framework (MOF) for the first time: X‐ray induced free radicals are accumulated on the organic linker and are subsequently stabilized in the conjugated fragment in the structure, while the metal center acts as the X‐ray attenuator. These radicals afford new emission features in both UV‐excited and X‐ray excited luminescence spectra, making it possible to establish linear relationships between the radiation dose and the normalized intensity of the new emission feature. The MOF‐based RPL materials exhibit advantages in terms of the dose detection range, reusability, emission stability, and energy threshold. Based on a comprehensive electronic structure and energy diagram study, the rational design and a substantial expansion of candidate RPL materials can be anticipated. [ABSTRACT FROM AUTHOR]

Radio‐photoluminescence (RPL) materials display a distinct radiation‐induced permanent luminescence center, and therefore find application in the detection of ionizing radiation. The current inventory of RPL materials, which were discovered by serendipity, has been limited to a small number of metal‐ion‐doped inorganic materials. Here we document the RPL of a metal–organic framework (MOF) for the first time: X‐ray induced free radicals are accumulated on the organic linker and are subsequently stabilized in the conjugated fragment in the structure, while the metal center acts as the X‐ray attenuator. These radicals afford new emission features in both UV‐excited and X‐ray excited luminescence spectra, making it possible to establish linear relationships between the radiation dose and the normalized intensity of the new emission feature. The MOF‐based RPL materials exhibit advantages in terms of the dose detection range, reusability, emission stability, and energy threshold. Based on a comprehensive electronic structure and energy diagram study, the rational design and a substantial expansion of candidate RPL materials can be anticipated. [ABSTRACT FROM AUTHOR]

Objective: Pancreatic cancer is a kind of high malignant tumor with a poor prognosis. The aim is to determine whether the dilated bile duct can be used to reconstruct the vessels.Methods: An animal model of jugular vein and portal vein reconstruction was established using the bile duct. A total of 20 landrace pigs were selected to undergo jugular vein reconstruction or portal vein reconstruction using the bile duct as a patch or bridge. The patency was evaluated by color Doppler, the reconstructed segments were removed and examined macroscopically and histologically at specified intervals, and the results were compared with synthetic vessels (IMPRA straight, 10s03-19).Results: The lumen was patent, although a low level thrombosis was observed when jugular or portal vein patching was used. For bridging, stenosis of the lumen was observed, and necrosis appeared when the bile duct was used for bridging, indicating that it is feasible to reconstruct the jugular vein and portal vein with a bile duct patch. However, the bridge was not feasible possibly due to loss of blood supply, and consequent necrosis and fibrosis.Conclusion: The bile duct is technically feasible, but the outcomes are unsatisfactory. [ABSTRACT FROM AUTHOR]

CxxC-finger protein 1 (CFP1)-mediated trimethylated histone H3 at lysine-4 (H3K4me3) during oocyte development enables the oocyte genome to establish the competence to generate a new organism. Nevertheless, it remains unclear to which extent this epigenetic modification forms an instructive component of ovarian follicle development. We investigated the ovarian functions using an oocyte-specific Cxxc1 knockout mouse model, in which the H3K4me3 accumulation is downregulated in oocytes of developing follicles. CFP1-dependent H3K4 trimethylation in oocytes was necessary to maintain the expression of key paracrine factors and to facilitate the communication between an oocyte and the surrounding granulosa cells. The distinct gene expression patterns in cumulus cells within preovulatory follicles were disrupted by the Cxxc1 deletion in oocytes. Both follicle growth and ovulation were compromised after CFP1 deletion, because Cxxc1 deletion in oocytes indirectly impaired essential signaling pathways in granulosa cells that mediate the functions of follicle-stimulating hormone and luteinizing hormone. Therefore, CFP1-regulated epigenetic modification of the oocyte genome influences the responses of ovarian follicles to gonadotropin in a cell-nonautonomous manner. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness of the periodontal continuing educational delivery mode via a periodontal alliance. Methods: An innovative continuing educational delivery mode via a periodontal alliance has been conducted using a periodontal alliance of 30 hospitals in 18 provinces of China. This delivery mode integrates several instructional methods, including lectures, case presentations, and interactive question and answer sessions, all of which were conducted through online platforms. The effectiveness of the mode was evaluated via a questionnaire that was administered to the participants. The questionnaire consisted of 13 closed‐ended questions and 2 open‐ended questions. Results: Of the 450 participants, 343 (76%) returned the questionnaire. Of the returned surveys, more than 92% provided positive feedback regarding the instructional methods of the program, stating that the techniques helped them study more efficiently and saved them time and money. More than 85% of the participants were satisfied with the instructional content and more than 90% of the participants considered the educational value of the program to be high, as it helped them identify gaps in knowledge, promoted their ability to establish treatment plans, and encouraged them to network with one another and thereby establish a supportive environment. With respect to the responses to the open‐ended questions, the participants claimed that the most useful aspects of the program were related to time and cost savings. The most frequent feedback with respect to improving the program was to include hands‐on courses and to divide the program into different levels. Conclusions: The participants responded positively to the program. The periodontal alliance delivery mode was determined to be an effective way to improve the quality of continuing dental education. [ABSTRACT FROM AUTHOR]

Non‐receptor tyrosine phosphatase 14 (PTPN14) has emerged as a novel tumour‐suppressor in a wide range of human cancer types. However, the role of PTPN14 in osteosarcoma remains undetermined. In the present study, we aimed to explore the expression pattern, biological function, and regulation of PTPN14 in osteosarcoma. Low PTPN14 expression levels were detected in osteosarcoma cells, and PTPN14 overexpression markedly decreased the proliferation, colony formation, and invasive potential of osteosarcoma cells. Bioinformatics analysis predicted PTPN14 as a potential target gene of microRNA‐4295 (miR‐4295), and this prediction was validated by a dual‐luciferase reporter assay. PTPN14 expression was negatively modulated by miR‐4295 in osteosarcoma cells. Moreover, PTPN14 expression was inversely correlated with miR‐4295 expression in osteosarcoma tissues. Notably, miR‐4295 inhibition significantly restricted the proliferation and invasion of osteosarcoma cells. PTPN14 overexpression or miR‐4295 inhibition increased the phosphorylation of Yes‐associated protein 1 (YAP1) and impeded YAP1 nuclear translocation, leading to inhibition of YAP1‐mediated transcriptional activity. However, the miR‐4925‐inhibition‐mediated antitumour effect was partially reversed by PTPN14 knockdown. Overall, these results demonstrate that PTPN14 is a miR‐4295 target gene and it exerts a tumour‐suppressive function in osteosarcoma cells via inactivation of YAP1. Our study uncovers a miR‐4295–PTPN14–YAP1 signalling pathway that may play a crucial role in the progression of osteosarcoma. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study was to evaluate the antiarthritic effects of different polar solvent extracts of Er Miao San (EMS) on model rats with adjuvant arthritis (AA) and screen the effective pats of EMS in the treatment of arthritis. Methods. Four different polar solvent extracts of EMS such as petroleum ether (PE), methylene chloride (CH2Cl2), ethyl acetate (EtOAc), and n-butanol (n-BuOH) were extracted and separated by different solvent polar extraction. Different polar parts of the aqueous extract of EMS were orally administered for 14 days to AA rats. Progression of clinical signs such as edema of paws and polyarthritis index was measured. The ankle joint changes were observed by pathological sections. ELISA was used to measure cytokines in the serum according to the manufacturer's instructions. UHPLC measured the effective parts of EMS. Results. Administration of EtOAc and CH2Cl2 parts remarkably inhibited the paw swelling, decreased the index of arthritis, decreased the body weight loss, and improved the changes of histopathology. Furthermore, the concentrations of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) were significantly lower, while the anti-inflammatory cytokine (IL-10) was remarkably higher compared with that in the model group. And the result of UHPLC analysis indicated that the effective parts of EMS contain berberine and atractylodin. Conclusions. EtOAc and CH2Cl2 are the effective parts of EMS that can improve arthritis. In particular, berberine and atractylodin may be responsible for the antiarthritic activity of EMS. This research provided pharmacological and chemical foundation for the application of EMS in treating rheumatoid arthritis (RA). [ABSTRACT FROM AUTHOR]