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The heterogeneity of macrophages influences the response to immune checkpoint inhibitor (ICI) therapy. However, few studies explore the impact of APOE+ macrophages on ICI therapy using single‐cell RNA sequencing (scRNA‐seq) and machine learning methods. The scRNA‐seq and bulk RNA‐seq data are Integrated to construct an M.Sig model for predicting ICI response based on the distinct molecular signatures of macrophage and machine learning algorithms. Comprehensive single‐cell analysis as well as in vivo and in vitro experiments are applied to explore the potential mechanisms of the APOE+ macrophage in affecting ICI response. The M.Sig model shows clear advantages in predicting the efficacy and prognosis of ICI therapy in pan‐cancer patients. The proportion of APOE+ macrophages is higher in ICI non‐responders of triple‐negative breast cancer compared with responders, and the interaction and longer distance between APOE+ macrophages and CD8+ exhausted T (Tex) cells affecting ICI response is confirmed by multiplex immunohistochemistry. In a 4T1 tumor‐bearing mice model, the APOE inhibitor combined with ICI treatment shows the best efficacy. The M.Sig model using real‐world immunotherapy data accurately predicts the ICI response of pan‐cancer, which may be associated with the interaction between APOE+ macrophages and CD8+ Tex cells. [ABSTRACT FROM AUTHOR]

In this study, a series of H‐bonded arylamide foldamers bearing benzoselenadiazole ends with solvent‐responsive properties have been synthesized. In dichloromethane or dimethyl sulfoxide solvents, the molecules exhibit meniscus or linear structures, respectively, which can be attributed to the unique intramolecular hydrogen bonding behavior evidenced by 1D 1H NMR and 2D NOESY spectra. UV‐vis spectroscopy experiments show that the absorption wavelength of H‐bonded arylamide foldamers are significantly red‐shifted due to the presence of benzoselenadiazole group. In addition, the crystal structures reveal that effective intermolecular dual Se ⋅ ⋅ ⋅ N interactions between benzoselenadiazole groups induce further assembly of the monomers. Remarkably, supramolecular linear and double helices structures are constructed under the synergistic induction of intramolecular hydrogen bonding and intermolecular chalcogen bonding. Additionally, 2D DOSY diffusion spectra and theoretical modelling based on density functional theory (DFT) are performed to explore the persistence of intermolecular Se ⋅ ⋅ ⋅ N interactions beyond the crystalline state. [ABSTRACT FROM AUTHOR]

In this study, a benzoselenadiazole- and pyridine-bifunctionalized hydrogen-bonded arylamide foldamer was synthesized. A co-crystallization experiment with 1,4-diiodotetrafluorobenzene showed that a new type of supramolecular double helices, which were induced by three orthogonal interactions, namely, three-center hydrogen bonding (O⋯H⋯O), I⋯N halogen bonding and Se⋯N chalcogen bonding, have been constructed in the solid state. This work presents a novel instance of multiple non-covalent interactions that work together to construct supramolecular architectures. [ABSTRACT FROM AUTHOR]

Pyroxenites, comprising only approximately 2 %–10 % by volume of the upper mantle, are among the most important lithological heterogeneity in the mantle. The formation of pyroxenite veins within peridotites is often attributed to migrating melts which provides an important mechanism for crust-mantle interaction. The Re–Os isotope system provides valuable insight into crust-mantle interaction, as there is a significant contrast in 187Os/188Os between crustal and mantle rocks. Previous Os isotope studies have shown that the forearc mantle wedge mainly consists of highly heterogeneous ancient peridotites. However, limited Re–Os isotope data of forearc mantle pyroxenites exist. Here, two types of mantle pyroxenites from the New Caledonia forearc ophiolite were selected for a comparative study. Contrasting microtextures and geochemical compositions support that these pyroxenites were formed by different processes. The Massif du Sud pyroxenites, hosted in harzburgites, have a cumulate origin and crystallized from boninitic melts generated by remelting of depleted mantle during subduction initiation, whereas the Tiebaghi pyroxenites within the host lherzolites are the products of melt-peridotite reactions. Both types of pyroxenites display highly fractionated highly siderophile element (HSE) patterns. The Massif du Sud pyroxenites are strongly enriched in palladium group platinum-group elements (PPGE) relative to iridium group platinum-group elements (IPGE) with remarkable positive Pt anomalies, which are similar to those of primitive arc lavas and mantle wedge pyroxenite xenoliths. In contrast, the Tiebaghi pyroxenites have flat IPGE but variable PPGE and Re patterns. Compared to the forearc mantle peridotites, the Tiebaghi pyroxenites have higher Os isotope ratios. Ancient basaltic melt percolation followed by long-term (>1 Ga) radiogenic ingrowth can successfully produce the observed correlations of 187Os/188Os with Os or Al 2 O 3 contents. Besides, the oldest Re-depletion model age (T RD) of ∼1.35 Ga has been obtained for the host lherzolites. Therefore, the Tiebaghi pyroxenites and their host lherzolites probably represent a stranded old mantle relict that has undergone ancient partial melting and melt percolation events. Our study supports the presence of highly radiogenic mantle domains in the forearc and provides significant constraints on the role of ancient basaltic melt percolation for generating mantle heterogeneity. [ABSTRACT FROM AUTHOR]

The recycling of subcontinental lithospheric mantle back into the asthenosphere during continental breakup is potentially a major but underappreciated process in plate tectonics. Here, we report major and trace elements for detrital peridotite minerals in carbonate breccias dredged from the Marion Rise, Southwest Indian Ridge. With an emphasis on the trace elements of the relatively abundant orthopyroxene detrital grains, the results show that a portion of pyroxene grains was likely derived from a mantle source that experienced hydrous melting and slab‐derived melt metasomatism above a subduction zone. This finding provides a novel view into the mantle geochemistry at midocean ridges, as well as evidence that Marion Rise is at least partially supported by chemically buoyant recycled refractory mantle wedge material. [ABSTRACT FROM AUTHOR]

Background: Immunotherapy combined with molecular targeted therapy is increasingly popular in patients with advanced hepatocellular carcinoma (HCC). However, immune-related adverse events(irAEs) brought on by immunotherapy increase the likelihood of side effects, thus it is important to look into ways to address this issue. Methods: Different metabolite patterns were established by analyzing metabolomics data in liver tissue samples from 10 patients(divided into severe and mild liver injury) before and after immuno-targeted therapy. After establishing a subcutaneous tumor model of HCC, the mice were divided into PBS group, ascorbic acid(AA) group, and anti-PD1 + tyrosine kinase inhibitor (TKI) group, anti-PD1 + TKI + AA group. Liver tissue were stained with hematoxylin-eosin staining(HE) and the content of aspartate transaminase (AST) and alanine transaminase(ALT) in blood were determined. The mechanism was confirmed by western blotting, mass cytometry, and other techniques. Results: Through metabolomics analysis, AA was significantly reduced in the sample of patients with severe liver injury caused by immuno-targeted therapy compared to patients with mild liver injury. The addition of AA in vivo experiments demonstrated a reduction in liver injury in mice. In the liver tissues of the anti-PD1 + TKI + AA group, the protein expressions of SLC7A11,GPX4 and the level of glutathione(GSH) were found to be higher compared to the anti-PD1 + TKI group. Mass cytometry analysis revealed a significant increase in the CD11b+CD44+ PD-L1+ cell population in the AA group when compared to the PBS group. Conclusions: AA could reduce liver injury by preventing hepatocyte SLC7A11/GPX4 ferroptosis and improve the immunotherapy effect of anti-PD1 by boosting CD11b+CD44+PD-L1+cell population in HCC. [ABSTRACT FROM AUTHOR]

Background: Bacillus subtilis is widely used in industrial-scale riboflavin production. Previous studies have shown that targeted mutagenesis of the ribulose 5-phosphate 3-epimerase in B. subtilis can significantly enhance riboflavin production. This modification also leads to an increase in purine intermediate concentrations in the medium. Interestingly, B. subtilis exhibits remarkable efficiency in purine nucleoside synthesis, often exceeding riboflavin yields. These observations highlight the importance of the conversion steps from inosine-5'-monophosphate (IMP) to 2,5-diamino-6-ribosylamino-4(3 H)-pyrimidinone-5'-phosphate (DARPP) in riboflavin production by B. subtilis. However, research elucidating the specific impact of these reactions on riboflavin production remains limited. Result: We expressed the genes encoding enzymes involved in these reactions (guaB, guaA, gmk, ndk, ribA) using a synthetic operon. Introduction of the plasmid carrying this synthetic operon led to a 3.09-fold increase in riboflavin production compared to the control strain. Exclusion of gmk from the synthetic operon resulted in a 36% decrease in riboflavin production, which was further reduced when guaB and guaA were not co-expressed. By integrating the synthetic operon into the genome and employing additional engineering strategies, we achieved riboflavin production levels of 2702 mg/L. Medium optimization further increased production to 3477 mg/L, with a yield of 0.0869 g riboflavin per g of sucrose. Conclusion: The conversion steps from IMP to DARPP play a critical role in riboflavin production by B. subtilis. Our overexpression strategies have demonstrated their effectiveness in overcoming these limiting factors and enhancing riboflavin production. [ABSTRACT FROM AUTHOR]

The dynamics and magma transport at the boundary between the upper and lower oceanic crusts (i.e., the dike–gabbro transition) are crucial for understanding the crustal accretion beneath mid-ocean ridges, which however have been studied at quite a few sites such as the East Pacific Rise and ophiolites like Troodos and Oman. Here we present detailed geological, petrological, and geochemical data for the dike–gabbro transition and associated basalts in the Yunzhug ophiolite, central Tibet, to constrain the complex magmatic processes in this specific horizon. The Yunzhug ophiolite contains a large (~ 20 km2) well-exposed sheeted dike complex, which is rooted in a dike–gabbro transition that consists of diverse lithologies, including diabase, gabbro, and minor porphyritic diabase. Petrographically, the Yunzhug gabbros could be grouped into the dominant Plg (plagioclase)-euhedral gabbros (euhedral–subhedral plagioclases enclosed in clinopyroxene oikocrysts) and a small amount of Cpx (clinopyroxene)-euhedral gabbros (with abundant euhedral clinopyroxenes). Plagioclases and their equilibrated melts of the two types of gabbros are similar, whereas clinopyroxenes and their equilibrated melts of the Cpx-euhedral gabbros are more primary and depleted than those of the Plg-euhedral gabbros. These petrographic and geochemical features suggest an earlier crystallization of clinopyroxene for the Cpx-euhedral gabbros, which is best explained by occasional water input in the magmatic system. Nevertheless, the modeled equilibrated melts of the two types of gabbros have compositions indistinguishable from the whole rock compositions of diabases and basalts, indicating a direct genetic linkage between these rocks. The unusual porphyritic diabases, on the other hand, provide evidence supporting for plagioclase accumulation and aggregation during magma upward migration, thus may have served as a unique way for magma to transport from the lower to upper crust. Studies of the Yunzhug ophiolite thus provide some key constraints on the complex magmatic processes in the oceanic dike–gabbro transition, regarding its dynamic accretion and magmatic plumbing mechanisms. [ABSTRACT FROM AUTHOR]

Context: This project performed quantum chemical computation, through kinetic and thermodynamic analyses to compare relative reactivity, reaction rate, and equilibrium composition from the possible pathways in connection with stabilizer-nitrodioxide reactions to determine the stability of the materials for practical application. Corresponding achievements have promoted the use of N-methyl-p-nitroaniline (MNA) and dinitrophenyl malonamide series (M3, M4, and M5) stabilizers as high priorities for selection. Methods: The Gaussian 09 program (G09) (Frisch et al 2009) and density functional theory (DFT) calculations with the B3LYP/6-31G(d,p) function were performed to obtain related geometric and thermodynamic energy data for the molecular systems in this study. The synchronous transit-guided quasi-Newton method (STQN) (Peng and Schlegel Isr J Chem 33:49, 1993) was applied through the QST3 procedure to identify single imaginary frequency-valued transition-state species. The related reaction rate constant (k) and pre-exponential factor (A) were obtained, based on transition state theory (Su 2008), using Eqs. 11 and 12. [ABSTRACT FROM AUTHOR]

Chemodynamic therapy (CDT) has great potential in cancer treatment, but its efficacy is limited due to non‐specificity, insufficient hydrogen peroxide (H2O2), and excessive glutathione (GSH) within the tumor microenvironment (TME). Here, an intelligent nanoplatform (Fe3O4@MnO2@NO@Au NPs, abbreviated as CD44FMNA) is reported for the treatment of breast cancer, which is constructed with Fe3O4 nanoparticles (NPs) as the core coated with manganese dioxide (MnO2) nanoshells encapsulating NO donors and gold nanoparticles (Au NPs) within the pores of MnO2, followed by the conjugation of targeting ligand anti‐CD44 mAb. The fabricated CD44FMNA initially remains inactive in normal cells, but after CD44 receptor ‐mediated MDA‐MB‐231 cell‐specific endocytosis, acidic TME can induce the decomposition of the MnO2 shell to release NO donors, thereby dually depleting the existing GSH in cells and enhancing the Fenton‐like reaction in a cascade manner. The generation of hydroxyl radicals (·OH) and the dual depletion of GSH can significantly weaken the GSH‐related antioxidant defense system (ADS) within MDA‐MB‐231 cells, accelerating apoptosis and cell death via the mitochondrial pathway. In addition, in vivo studies demonstrate that CD44FMNA can effectively inhibit tumor growth with good biosafety. Therefore, this nanoplatform may provide an effective therapy for the treatment of breast cancer. [ABSTRACT FROM AUTHOR]

Unlike their eruptive counterparts, plutonic rocks often experience post-cumulus evolution prior to their final solidification. These processes have the potential to exert significant control on the distributions of elements and their isotopic compositions of plutonic rocks. However, our understanding in these effects remains limited, particularly for metal stable isotopes. Here, we carried out high-precision δ65Cu measurements for a suite of primitive to evolved cumulates from the Kane area, 23oN of Mid-Atlantic Ridge. Most mid-ocean ridge basalts (MORBs) exhibit uniformly bulk silicate Earth (BSE)-like δ65Cu of + 0.09 ± 0.08 ‰, indicating limited Cu isotopic fractionation in crustal magma reservoirs prior to melt extraction. However, our new Cu isotopic data on these cumulates show that large Cu isotopic variations (δ65Cu = -0.6 ‰ to + 0.9 ‰) occur in variably evolved cumulates (MgO/total FeO < 3.0), while the most primitive cumulates (MgO/total FeO > 3.0) exhibit BSE-like δ65Cu (+0.06 ± 0.06 ‰). Petrological and geochemical observations indicate limited hydrothermal effects on Kane cumulate Cu isotopes. Modeling results indicate that the variable δ65Cu in Kane cumulates are unlikely to result from magmatic processes during the cumulus stage. Instead, the large Cu isotopic variation in Kane cumulates requires post-cumulus melt evolution involving fractionation between sulfide and intercumulus melts at relatively low temperatures. Textures and mineral chemistry indicate pervasive post-cumulus modifications of Kane cumulates by porous melt flow. Thermodynamic calculations indicate that intercumulus melts persist at temperatures even to 200 °C lower than the initial liquidus temperatures. Our data indicate that lower temperatures in the post-cumulus melt evolution and lower sulfide Ni contents result in lower sulfide-silicate melt Cu isotope fractionation factor (α sulfide-melt), then causing greater Cu isotopic variations in cumulates. We suggest that post-cumulus melt evolution reconcile both the Cu depletion and large Cu isotope fractionation in oceanic cumulates that are unexpected by a simple process of crystal accumulation from MORBs. This study highlights the essential role of post-cumulus evolution in controlling metal budget and their stable isotope fractionation during intra-crustal differentiation, which might also be applied to island arc and continental settings. [ABSTRACT FROM AUTHOR]

This article discusses the role of small quantities of cartilage sodium channels in osteoarthritis (OA). The researchers found that the sodium channel Nav1.7 is present and elevated in human OA chondrocytes, and its deletion or blockade can attenuate the progression of OA and alleviate OA pain. The study also highlights the need for further investigation into the molecular mechanisms underlying the role of Nav1.7 in OA progression. The authors suggest that targeting Nav1.7 could be a potential therapeutic approach for treating OA. [Extracted from the article]

As the melting residue of the asthenosphere at ocean ridges, the oceanic mantle lithosphere is initially depleted, which might be re-enriched by various types of melts. However, the metasomatic enrichments in the sub-ridge mantle lithosphere are generally assumed to be limited, because these melts have low abundances of incompatible elements. In this study, we report a case of extreme metasomatic enrichment in abyssal peridotites from the Atlantis Bank oceanic core complex on the Southwest Indian Ridge. We identify two types of metasomatized peridotites (Type 1 and 2) and a clinopyroxenite, which show different degrees of interaction with evolved melts. Type 1 peridotite exhibits strong incompatible element zonation and negative Eu anomalies in clinopyroxene, indicating a short-term percolation of a modestly evolved mid-ocean ridge basalt (MORB). Type 2 peridotite shows textural and trace element features consistent with the impregnation of a highly evolved, oxide-saturated MORB magma. The clinopyroxenite shows remarkable enrichments in iron and incompatible trace elements and negative Eu anomalies in clinopyroxene and contains abundant zircon and apatite, which imply reaction with an extremely evolved Fe–Zr–P-rich melt. We attribute such extreme mantle metasomatic enrichments to the lateral infiltration of variably evolved melts from a local magmatic center, which is now exposed as the Atlantis Bank gabbroic massif. As slow- and ultraslow-spreading ridges exhibit similarly discontinuous lower crust, the intervening shallow mantle between local magmatic centers may have been pervasively metasomatized by the evolved melts, leading the way for substantial mantle enrichment. [ABSTRACT FROM AUTHOR]

Objective: We aimed to explore the geographic differences in psychological symptoms, sleep quality, and quality of life (QoL) among adult patients with inflammatory bowel disease (IBD). Methods: A unified questionnaire was developed to collect data on psychological status and QoL of IBD patients from 42 hospitals across 22 provinces, municipalities, and autonomous regions in China's mainland from September 2021 to May 2022. Results: A total of 2478 patients with IBD were surveyed. The proportions of patients with anxiety (28.5% vs 23.1%), depression (32.3% vs 27.8%), and poor QoL (44.8% vs 32.2%) were significantly higher in patients from the northern region compared to the southern region (all P < 0.05). In the western region, the proportions of patients with anxiety (31.9% vs 23.0%), depression (37.7% vs 26.7%), sleep disturbances (64.5% vs 58.5%), and poor QoL (44.9% vs 34.8%) were significantly higher than in the eastern and central regions (all P < 0.01). Patients from inland regions had significantly higher rates of anxiety (27.1% vs 23.3%), depression (32.5% vs 26.0%), sleep disturbance (62.0% vs 57.7%), and poor QoL (43.5% vs 29.9%) compared to those from coastal regions (all P < 0.05). In economically underdeveloped areas, the proportions of patients with depression (33.1% vs 28.5%) and poor QoL (52.0% vs 32.4%) were significantly higher than in economically (relatively) developed areas (both P < 0.05). Conclusion: There are significant geographic differences in psychological symptoms, sleep quality, and QoL among Chinese patients with IBD, which might provide valuable insights for global IBD research and clinical practice. [ABSTRACT FROM AUTHOR]

An oxidant‐free photocatalytic [2+2+m] cyclization of 2‐cyanoaryl acrylamides with 2‐bromocarbonyls is reported, enabling the assembly of biologically important N‐heterocycle‐fused quinolinones including benzo[1,6]naphthyridinones and pyrrolo[3,2‐c]‐quinolines. This photocatalytic protocol proceeds through a radical relay pathway including alkene difunctionalization along with an intramolecular cyano insertion and subsequent site‐specific functionalization of inert C(sp3)−H bond enabled by cyano‐derived iminyl radical‐mediated 1,n‐hydrogen atom transfer. Notably, this transformation selectively formed two distinct C−C bonds, one C−N bond, and one quaternary carbon center in a one‐pot procedure. [ABSTRACT FROM AUTHOR]

Pyroxenite veins are commonly observed in the mantle section of ophiolites, reflecting a variety of melts that percolate through the mantle, react, and finally crystallize in the lithosphere. To better understand the formation mechanism of the pyroxenite veins and associated peridotites, we conducted an integrated petrological and geochemical study of a suite of orthopyroxenite, websterite, and composite clinopyroxenite–orthopyroxenite veins in residual peridotites from the Dazhuqu ophiolite (Southern Tibet, China). Both orthopyroxene and clinopyroxene in pyroxenites are characterized by high Mg#, low Al2O3 concentrations, and depleted patterns of incompatible trace elements. This suggests that parental melts of the pyroxenites could be formed by re-melting of a previously depleted mantle source. We observed systematic variations in the major and trace element compositions of clinopyroxene and orthopyroxene across the pyroxenite–harzburgite sequences. Through trace element modeling, we have established a model for the formation of pyroxenite veins and associated harzburgites. According to this model, hydrous and aggregated melts were expelled from the tip of the dunite channels and subsequently injected into the lithosphere via fractures. The infiltrating melts then underwent diffusional loss of water into the residual harzburgites within the asthenosphere, which in turn promoting partial melting of the harzburgite. The pyroxenite veins were formed by mixing the infiltrating channel melt and matrix melt derived from partially molten harzburgite. This formation model can be applied to explain the pyroxenite–harzburgite and dunite–pyroxenite–harzburgite sequences in the Yarlung-Tsangbo ophiolite and other ophiolites around the world. [ABSTRACT FROM AUTHOR]

Offline handwritten text recognition (HTR) is a long-standing research project for a wide range of applications, including assisting visually impaired users, humans and robot interactions, and the automatic entry of business documents. However, due to variations in writing styles, visual similarities between different characters, overlap between characters, and source document noise, designing an accurate and flexible HTR system is challenging. The problem becomes serious when the algorithm has a low learning capacity and when the text used is complex and has a lot of characters in the writing system, such as Ethiopic script. In this paper, we propose a new model that recognizes offline handwritten Ethiopic text using a gated convolution and stacked self-attention encoder–decoder network. The proposed model has a feature extraction layer, an encoder layer, and a decoder layer. The feature extraction layer extracts high-dimensional invariant feature maps from the input handwritten image. Using the extracted feature maps, the encoder and decoder layers transcribe the corresponding text. For the training and testing of the proposed model, we prepare an offline handwritten Ethiopic text-line dataset (HETD) with 2800 samples and a handwritten Ethiopic word dataset (HEWD) with 10,540 samples obtained from 250 volunteers. The experiment results of the proposed model on HETD show a 9.17 and 13.11 Character Error Rate (CER) and Word Error Rate (WER), respectively. However, the model on HEWD shows an 8.22 and 9.17 CER and WER, respectively. These results and the prepared datasets will be used as a baseline for future research. [ABSTRACT FROM AUTHOR]

Bacterial wound infections are a serious threat due to the emergence of antibiotic resistance. Herein, we report an innovative hybrid nanozyme independent of antibiotics for antimicrobial wound healing. The hybrid nanozymes are fabricated from ultra-small Au NPs via in-situ growth on metal-organic framework (MOF)-stabilised Fe3O4 NPs (Fe3O4@MOF@Au NPs, FMA NPs). The fabricated hybrid nanozymes displayed synergistic peroxidase (POD)-like activities. It showed a remarkable level of hydroxyl radicals (·OH) in the presence of a low dose of H2O2 (0.97 mM). Further, the hybrid FMA nanozymes exhibited excellent biocompatibility and favourable antibacterial effects against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria. The animal experiments indicated that the hybrid nanozymes promoted wound repair with adequate biosafety. Thus, the well-designed hybrid nanozymes represent a potential strategy for healing bacterial wound infections, without any toxic side effects, suggesting possible applications in antimicrobial therapy. [ABSTRACT FROM AUTHOR]

In this paper, two types of solid phase 2D and 3D XBOFs were selectively constructed from identical building blocks of tetraphenylmethane tetrapyridine derivative and 1,4-diiodotetrafluorobenzene by changing the crystallization solvent. This 3D XBOF is a novel hybrid supramolecular organic framework with the synergistic control of hydrogen and halogen bonds. [ABSTRACT FROM AUTHOR]

Recent studies have discovered that functional connections are impaired in patients with Parkinson's disease (PD) accompanied by hallucinations (PD-H), even at the preclinical stage. The cerebellum has been implicated in playing a role in cognitive processes. However, the functional connectivity (FC) between the cognitive sub-regions of the cerebellum in PD patients with hallucinations needs further clarification. Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected from three groups (17 PD-H patients, 13 patients with Parkinson's disease not accompanied by hallucinations (PD-NH), and 26 healthy controls (HC)). The data were collected in this study to investigate the impact of cerebellar FC changes on cognitive performance. Additionally, we define cerebellar FC as a training feature for classifying all subjects using Support Vector Machines (SVMs). We found that in the PD-H patients, there was an increase in FC within the left side of the precuneus (PCUN) compared to the HC. Additionally, there was an increase in FC within the bilateral opercular part of the inferior frontal gyrus (IFGoprec) and triangular part of the inferior frontal gyrus (IFCtriang), as well as the left side of the postcentral gyrus (PoCG), inferior parietal lobe (IPL), and PCUN compared to the PD-NH patients. In the machine learning training results, cerebellar FC has also been proven to be an effective biomarker feature, achieving a recognition rate of over 90% for PD-H. These findings indicate that the cortico-cerebellar FC in PD-H and PD-NH patients was significantly disrupted, with different patterns of distribution. The proposed pipeline offers a promising, low-cost alternative for diagnosing preclinical PD-H and may also be beneficial for other degenerative brain disorders. [ABSTRACT FROM AUTHOR]

Molting is an essential operation in the life of every lobster, and observing this process will help us to assist lobsters in their recovery. However, traditional observation consumes a significant amount of time and labor. This study aims to develop an autonomous AI-based robot monitoring system to detect molt. In this study, we used an optimized Yolov5s algorithm and DeepLabCut tool to analyze and detect all six molting phases such as S1 (normal), S2 (stress), S3–S5 (molt), and S6 (exoskeleton). We constructed the proposed optimized Yolov5s algorithm to analyze the frequency of posture change between S1 (normal) and S2 (stress). During this stage, if the lobster stays stressed for 80% of the past 6 h, the system will assign the keypoint from the DeepLabCut tool to the lobster hip. The process primarily concentrates on the S3–S5 stage to identify the variation in the hatching spot. At the end of this process, the system will re-import the optimized Yolov5s to detect the presence of an independent shell, S6, inside the tank. The optimized Yolov5s embedded a Convolutional Block Attention Module into the backbone network to improve the feature extraction capability of the model, which has been evaluated by evaluation metrics, comparison studies, and IoU comparisons between Yolo's to understand the network's performance. Additionally, we conducted experiments to measure the accuracy of the DeepLabCut Tool's detections. [ABSTRACT FROM AUTHOR]

Visual Question Answering (VQA) is a challenging task that requires a fine-grained understanding of both the visual content of images and the textual content of questions. Conventional visual attention model, which is designed primarily from the perspective of attention mechanism, lacks the ability to reason about relationships between visual objects and ignores the multimodal interactions between questions and images. In this work, we propose a combined both graph convolutional network and co-attention network to circumvent the aforementioned problem. The model employs binary relational reasoning as the graph learner module to learn a graph structure representation that captures relationships between visual objects and learns image representation related to the specific question that has an awareness of spatial location via spatial graph convolution. After that, we perform parallel co-attention learning by passing image representations and features of question words through a deep co-attention module. Experiment results demonstrate that the Overall accuracy of our model delivers 68.67 % on the test-std set of the benchmark VQA v2.0 dataset, which outperforms most existing models. [ABSTRACT FROM AUTHOR]

Hydraulic structures (such as dams and aqueducts) can suffer from damages, such as cracks and collapse due to natural aging as well as the impact of natural disasters (such as earthquakes and floods). Determining underwater damage is generally not easy because of significant concealment and safety hazards. Remotely operated vehicles (ROVs) have gradually become capable assistants for the regular underwater maintenance of hydraulic structures. With disturbances from undercurrents and propeller reactions, achieving precise positioning of ROVs has always been a complicated technical problem, and it is also one of the important factors affecting underwater inspections and repair accuracy. To address the environmental disturbances during ROV dynamic positioning, a fuzzy predictive control algorithm combining fuzzy control and model predictive control is proposed in this paper. This algorithm can dynamically adjust the power output of propellers in real-time according to the undercurrent data measured by sensors and carry out differential correction until the ROV reaches the predetermined position. Moreover, the aim of this paper is to analyze disturbances in the longitudinal (X), lateral (Y), and depth (Z) directions during the motion of the ROV. The parameters are adjusted through the algorithm to simulate the dynamic positioning of the ROV's spatial movements. By setting different external environmental conditions, the power adjustment strategy and different dynamic positioning performances of ROVs can be obtained to enhance the adaptability of ROVs in complex environments and their stability in underwater inspection and repair and improve their underwater operation quality and efficiency. [ABSTRACT FROM AUTHOR]

Ultramafic rocks of the Yarlung-Tsangpo ophiolites (lherzolites, harzburgites, dunites and pyroxenites) have been interpreted as lithospheric mantle relics of the Cretaceous Neo-Tethys Ocean (NTO). Studying these rocks could provide key constraints on the NTO's evolution and invaluable information on sub-ridge mantle heterogeneity. The Xiugugabu ophiolite crops out in the western segment of the Yarlung-Tsangpo Suture Zone (YTSZ) and is dominantly composed of mantle components with minor crustal material. Here we report a comprehensive field, petrological and geochemical study of the ultramafic rocks from this ophiolitic massif. The lherzolites and harzburgites are less refractory than the Xigaze ultramafic rocks in the middle part of the YTSZ. Petrology and simple models are consistent with 10–20% fractional melting from an anhydrous, depleted mantle source, within the spinel and garnet stability fields. Part of dunites (Dunite-II) and pyroxenites formed during pervasive melt impregnation into host peridotites and record the modal and geochemical effects of post-melting melt–rock interactions. The discrepancy of light rare earth element (LREE) contents between whole rocks and their two pyroxene components in peridotites indicates that they have trapped interstitial melts along grain boundaries at a post-melting stage. These melts were potentially derived from shallow sources in spinel domains. Bulk rock osmium isotopic compositions suggest that the pyroxenites and part of the dunites are highly radiogenic. These enriched Os signatures are likely imposed by percolating melts derived from mantle sources hybridized by ancient recycled crustal materials. When comparing with results from previous studies of other YTSZ peridotites with ultra-depleted nature and unradiogenic Os isotopic compositions, we conclude that the sub-ridge mantle beneath the Neo-Tethyan Ocean was heterogeneous, with not only unradiogenic but also highly radiogenic mantle domains. [ABSTRACT FROM AUTHOR]

Construction of oceanic crusts in ultraslow-spreading ridges are controlled by detachment faults, but the specific ways they are determined by detachments remain unclear. Abundant ophiolite massifs discovered along the Yarlung-Tsangpo Suture Zone, southern Tibet, are considered to represent ultraslow-spreading centers of the Cretaceous Neo-Tethys ocean. The presence of various mafic blocks within the ophiolitic mélange beneath the lithospheric mantle provides evidence of the entire processes involved in crustal generation. Therefore, in this study geochemical investigations on these mafic blocks from the southern Luqu (Xigaze) ophiolitic mélanges were conducted to shed new lights on the petrogenesis of mafic crust rocks in ultraslow-spreading settings. Geochronological results via zircon U–Pb dating gave evidence for their coeval formation to other Yarlung-Tsangpo ophiolitic crust rocks in the Early Cretaceous (ca. 120–130 Ma). Geochemistry and Sr–Nd–Hf isotopes document depleted and primitive characteristics, revealing that these mafic rocks were crystallized from residual melts experienced substantial fractional crystallization following along liquid lines of descent of H2O-poor magmas. However, amphiboles are pervasive throughout our samples, which is in contrast with expectations of clinopyroxene and plagioclase as dominant liquidus phases of anhydrous magma. Textures of replacement of clinopyroxene by magnesio-hornblende and their higher contents of trace elements and Eu negative anomalies support that the amphiboles crystallized during transition from dry magma to hydrous one, indicative of water additions to solidifying melts. Based on the tectonic settings of ultraslow-spreading centers, we proposed a model in which seawater-derived fluids induced through detachment faults could be responsible for the generation of ultraslow-spreading crust. [ABSTRACT FROM AUTHOR]

This document is a letter published in the Annals of Hematology. It describes a case study of a 53-year-old male patient who presented with skin color abnormalities, anemia, splenomegaly, and abnormal liver function. The patient had a history of type 2 diabetes mellitus and exhibited stunted development. Various tests were conducted, including genetic tests, liver function tests, and imaging scans, which led to the diagnosis of congenital dyserythropoietic anemia type I (CDAI). The study also identified a novel pathogenic variant in the CDAN1 gene using whole exome sequencing and bioinformatics analysis. The authors conclude that this study provides a template for the diagnosis of rare hereditary blood diseases or other unknown genetic disorders. [Extracted from the article]

Lung adenocarcinoma (LUAD) is the most common histological type of lung cancer. In recent years, cell senescence emerges as a potential therapeutic target of cancer therapy. However, the role of cell senescence in LUAD has not been comprehensively unveiled. One single cell RNA sequencing (scRNA-seq) dataset (GSE149655) and two bulk RNA-seq datasets (TCGA and GSE31210) of LUAD were included. Seurat R package was used to process scRNA-seq data and identify immune cell subgroups. Single sample gene set enrichment analysis (ssGSEA) was performed to calculate enrichment score of senescence-related pathways. Senescence-based molecular subtyping for LUAD samples was conducted through unsupervised consensus clustering. pRRophetic package was introduced to analysis drug sensitivity. The senescence-associated risk model was established using univariate regression and stepAIC methods. Western blot, RT-qPCR, immunofluorescence assay and CCK-8 were used to explore the effect of CYCS in LUAD cell lines. Malignant immune cells had remarkedly higher enrichment of senescence-related pathways than non-malignant cells. P53 signaling and DNA damage telomere stress induced senescence pathways were found to be significantly activated in LUAD samples compared with normal samples. We identified two clusters (clust1 and clust2) based on senescence-related genes. Clust1 had severe genomic instability, aggravated senescent features, and low immune and stromal infiltration. The senescence-associated risk model including CASP9, CHEK1, CYCS, SERPINE1, SESN2, TP53I3, LMNB1, RAD50 and TERF2IP, was effective to distinguish high- and low-risk groups. Moreover, low-risk group exhibited sensitive responses to immunotherapy and chemotherapeutic drugs. In vitro experiments results showed that CYCS expression was increased and promoted cell viability in LUAD cell lines. This study explored the important role of senescence in LUAD progression, and confirmed the potential of senescence-related genes in predicting LUAD prognosis and response to immunotherapy and chemotherapy. [ABSTRACT FROM AUTHOR]

Image-defined risk factors (IDRF) in neuroblastoma have been developed to predict tumor resectability and surgical complications; however, the potential prognostic value of IDRF in neuroblastoma has been variably reported. Previous studies did not report the IDRF status separately from the International Neuroblastoma Risk Group (INRG) stage. Moreover, the association between IDRF and clinical and pathological factors has not been discussed further. In this retrospective study, we investigated the clinical and biological features of neuroblastoma at different INRG stages based on IDRF. Event-free survival (EFS) and overall survival (OS) related to the INRG stage were analyzed using log-rank tests, and the prognostic value of the IDRF number and type was also evaluated. Among 72 patients, 182 IDRF at diagnosis were found in 79.2%. The distribution of the INRG stages was 10 L1 (13.9.0%), 25 L2 (34.7%), and 37 M/MS (51.4%). Patients with stage M/Ms had a larger tumor volume, a higher percentage of age ≥ 18 months, elevated lactate dehydrogenase (LDH) level, elevated ferritin level, and a higher percentage of COG high-risk compared with stage L1 and L2 patients. EFS and OS were similar for stage L1 and L2 tumors but were significantly poorer for metastatic disease. However, EFS (P = 0.06) and OS (P = 0.07) were similar for IDRF-negative and positive neuroblastomas. Patients with stage M/Ms with IDRF-positive had poorer EFS (P = 0.001) and OS (P < 0.001) compared with patients in stage L2. An IDRF ≥ 4, vascular IDRF, and infiltrative IDRF of the tumor were significant indicators of poor prognosis. Conclusion: Our study indicates that increasing the INRG stages based on IDRF is associated with various unfavorable clinical features of neuroblastoma. The principal determinant of survival in neuroblastoma is the presence of metastatic disease more than IDRF alone at diagnosis. Both the number and type of IDRF have important clinical significance in the protocol planning of neuroblastoma, rather than just considering the absence or presence of IDRF. What is Known: • The International Neuroblastoma Risk Group Staging System (INRGSS) now employs image-defined risk factors (IDRFs) to stratify and stage disease. • The presence of IDRF at diagnosis are associated with higher rates of operative complications and incomplete surgical resection. What is New: • The principal determinant of survival from neuroblastoma is the presence of metastatic disease at diagnosis, more than IDRF alone. • IDRF number and type should also be considered during the diagnosis and treatment planning of neuroblastoma, rather than just considering the absence or presence of IDRF. [ABSTRACT FROM AUTHOR]

In this work, a polarization conversion metasurface is proposed, which can convert linearly polarized electromagnetic (EM) waves into cross-polarized waves in ultra-wideband at high polarization conversion efficiency. The proposed sandwiched metasurface, composed of a top anisotropic resonator structure, an intermediate dielectric substrate, and a bottom metallic ground, has an extremely thin thickness (only 6.6% of the longest wavelength of the working frequency range). Both numerical simulation and experimental results illustrate that the metasurface can work in the ultra-wideband (ranging from 9.04 to 20.83 GHz) with a high polarization conversion ratio (>0.9). Polarization conversion in a wide bandwidth is attributed to multiple resonances in the operating frequency range. Additionally, the proposed metasurface also shows good performance for oblique incidence. It is expected that the designed metasurface will be more convenient for integration within ultra-thin EM devices. [ABSTRACT FROM AUTHOR]

With the depletion of fossil fuel energy and both the slow development and low utilization rate of new eco-friendly energy, finding new ways to efficiently store energy has become a research hotspot. Presently, polyethylene glycol (PEG) is an excellent heat storage material, but it is a typical solid-liquid phase change material (PCM) with a risk of leakage during phase transition. A combination of wood flour (WF) and PEG can effectively eliminate the risk of leakage after the melting of PEG. However, WF and PEG are both flammable materials, which impedes their application. Therefore, it is of great significance to expand their application by forming composites from among PEG, supporting mediums, and flame-retardant additives. This will improve both their flame retardancy and phase change energy storage performance, and will also lead to the preparation of excellent flame-retardant phase change composite materials with solid-solid phase change characteristics. To address this issue, ammonium polyphosphate (APP), organic modified montmorillonite (OMMT), and WF were blended into PEG in specific proportions to prepare a series of PEG/WF-based composites. Both thermal cycling tests and thermogravimetric analysis results demonstrated that the as-prepared composites had good thermal reliability and chemical stability. In addition, during differential scanning calorimetry tests, the PEG/WF/8.0APP@2.0OMMT composite presented the highest melting latent heat (176.6 J/g), and its enthalpy efficiency reached more than 98.3%. The PEG/WF/8.0APP@2.0OMMT composite also exhibited superior thermal insulation performance when compared to the pure PEG/WF composite. Furthermore, the PEG/WF/8.0APP@2.0OMMT composite exhibited a significant 50% reduction in peak heat release rate as a result of the synergistic effect between OMMT and APP in the gas and condensed phases. This work offers a useful strategy for the fabrication of multifunctional phase-change material, which is expected to broaden its industrial applications. [ABSTRACT FROM AUTHOR]

Objective: To explore the gender differences in the psychological symptoms, sleep quality, and quality of life of patients with inflammatory bowel disease (IBD). Methods: A unified questionnaire was developed to collect clinical data on the psychology and quality of life of IBD patients from 42 hospitals in 22 provinces in China from September 2021 to May 2022. The general clinical characteristics, psychological symptoms, sleep quality, and quality of life of IBD patients of different genders were analyzed via a descriptive statistical analysis. A multivariate logistic regression analysis was conducted, and independent influencing factors were screened to construct a nomogram to predict the quality of life. The consistency index (C-index), receiver operating characteristic (ROC) curve, area under the ROC curve (AUC), and calibration curve were used to evaluate the discrimination and accuracy of the nomogram model. Decision curve analysis (DCA) was used to evaluate the clinical utility. Results: A total of 2478 IBD patients (1371 patients with ulcerative colitis (UC) and 1107 patients with Crohn's disease (CD)) were investigated, including 1547 males (62.4%) and 931 females (37.6%). The proportion of anxiety in females was significantly higher than in males (IBD: 30.5% vs. 22.4%, p < 0.001; UC: 32.4% vs. 25.1%, p = 0.003; CD: 26.8% vs. 19.9%, p = 0.013), and there were differences in the severity of anxiety between the genders (IBD: p < 0.001; UC: p < 0.001; CD: p = 0.050). The proportion of depression in females was higher than in males (IBD: 33.1% vs. 27.7%, p = 0.005; UC: 34.4% vs. 28.9%, p = 0.031; CD: 30.6% vs. 26.6%, p = 0.184), and there were differences in the severity of depression between the genders (IBD: p = 0.004; UC: p = 0.022; CD: p = 0.312). The proportion suffering from sleep disturbances among females was slightly higher than among males (IBD: 63.2% vs. 58.4%, p = 0.018; UC: 63.4% vs. 58.1%, p = 0.047; CD: 62.7% vs. 58.6%, p = 0.210), and the proportion of females with a poor quality of life was higher than that of males (IBD: 41.8% vs. 35.2%, p = 0.001; UC: 45.1% vs. 39.8%, p = 0.049; CD: 35.4% vs. 30.8%, p = 0.141). The AUC values of the female and male nomogram prediction models for predicting poor quality of life were 0.770 (95% CI: 0.7391–0.7998) and 0.771 (95% CI: 0.7466–0.7952), respectively. The calibration diagrams of the two models showed that the calibration curves fitted well with the ideal curve, and the DCA that showed nomogram models could bring clinical benefits. Conclusions: There were significant gender differences in the psychological symptoms, sleep quality, and quality of life of IBD patients, suggesting that females need more psychological support. In addition, a nomogram model with high accuracy and performance was constructed to predict the quality of life of IBD patients of different genders, which is helpful for the timely clinical formulation of personalized intervention plans that can improve the prognosis of patients and save medical costs. [ABSTRACT FROM AUTHOR]

The incomplete understanding of Mg isotope fractionation behavior between calcite and aqueous solutions has limited the interpretation and application of Mg isotope data in natural carbonates. In this study, we performed a series of aragonite-to-calcite conversion experiments under hydrothermal conditions to investigate the effects of temperature and organic ligands on elemental and isotopic partitioning of Mg between calcite and aqueous solutions. The experiments produced magnesian calcite via a dissolution-and-precipitation process. The Mg distribution coefficients between solid and aqueous solution (D Mg , 0.08 to 0.21) showed negative correlations with Sr distribution coefficients (D Sr , 0.04 to 0.48), as well as the proportion of calcite in the bulk solid, which indicates mixing of calcite (Mg-rich and Sr-poor) and aragonite (Sr-rich and Mg-poor) in the solid phases. The apparent Mg isotope fractionation factors between solid and aqueous solutions (Δ26Mg solid-soln) show a positive correlation with reaction temperatures, where Δ26Mg solid-soln increases from ca. −1.84 ‰ at 98 °C to −1.35 ‰ at 170 °C. In addition, the presence of oxalate contributed to slightly lower Δ26Mg solid-soln values, which is interpreted to be related to the isotopic effect of Mg-oxalate speciation. Based on the experimental results, we propose a temperature-dependent function for Mg isotope fractionation between calcite and free Mg-aquo ions (i.e., Mg(H 2 O) 6 2+): Δ26Mg cal-Mg(aq) = (−0.17 ± 0.01) × 106/T2- (0.52 ± 0.08). This equation is applicable to a wide range of temperatures, especially at hydrothermal conditions, thus enabling interpretations of Mg isotope data from calcite of hydrothermal and burial origin. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus (DM) is a comorbidity commonly presenting with metabolic-dysfunction-associated fatty liver disease (MAFLD); however, few tests for interaction have been reported. Our target was to evaluate the prognostic implications of DM in patients with different forms of MAFLD. Methods: Using data from the Third National Health and Nutrition Examination Survey (NHANES III) in the United States, we screened 14,797 participants aged 20–74 who received ultrasound examinations from 1988–1994. Among them, 4599 patients met the diagnosis of MAFLD, and we defined mortality as the outcome event. Survival analysis of competitive risk events was performed using Cox regression and sub-distributed risk ratio (SHR). Results: During 21.1 years of follow-up, cardiovascular diseases seemed to be the most common cause of death among MAFLD patients. Of them, DM was present in 25.48% and was independently associated with increased risk of all-cause mortality (HRs: 1.427, 95% CIs: 1.256–1.621, p < 0.001) and cause-specific mortality (cardiovascular-related mortality (HRs: 1.458, 95% CIs: 1.117–1.902, p = 0.005), non-cardiovascular-related mortality (HRs: 1.423, 95% CIs: 1.229–1.647, p < 0.001), and non-cancer-related mortality (HRs: 1.584, 95% CIs: 1.368–1.835, p < 0.001), respectively). Surprisingly, this association was more significant for young patients (p-value for interaction <0.001). Moreover, DM had a greater risk of all-cause and cause-specific mortality among overweight and obese MAFLD patients (p-value for interaction <0.001). Conclusions: DM increased the risk of all-cause and cause-specific mortality (cardiovascular-related, non-cardiovascular-related, and non-cancer-related) in MAFLD patients, especially in younger patients with excess obesity. [ABSTRACT FROM AUTHOR]

An important mechanism of carbonate mineral growth is dissolution-reprecipitation, including the transformation of amorphous precursor to crystalline carbonates, and coarsening (ripening) of fine carbonate crystals. However, the mechanistic details of cation exchange associated with carbonate mineral growth via a dissolution-reprecipitation process are still not well understood. In this study, we used Mg isotopes to probe the exchange of Mg between aqueous solutions and norsethite [BaMg(CO3)2] by systematic synthesis experiments. Norsethite is a model double carbonate, with a general formula of AB(CO3)2, where A and B stand for two different divalent ions. Formation of norsethite is comprised of three stages, including: (1) precipitation of barium-magnesium (Ba-Mg) amorphous carbonate; (2) transformation of Ba-Mg amorphous carbonate to nano-crystalline norsethite by fast dissolution-reprecipitation; and (3) coarsening (ripening) of nano-norsethite by slow dissolution-reprecipitation. Magnesium isotopes displayed distinct fractionation behaviors in each of the three stages. The Mg isotope fractionation factors (Δ26Mgsolid-aq) associated with precipitation of Ba-Mg amorphous carbonate were slightly negative and temperature-dependent, from –0.83‰ at 30 °C to –0.53‰ at 70 °C. During the transformation of Ba-Mg amorphous carbonate to nano-crystalline norsethite, isotopically light Mg isotopes were further enriched in the solid phase, with apparent Δ26Mgsolid-aq decreasing to –2.12‰ at 30 °C and –1.56‰ at 70 °C. In the ripening stage, norsethite became isotopically heavier, with Δ26Mgsolid-aq increasing up to –1.95‰ at 30 °C and –1.17‰ at 70 °C. The experimental results show that non-equilibrium isotope fractionation occurred during the transformation of amorphous carbonate to nano-crystalline norsethite (i.e., fast dissolution-reprecipitation). By contrast, the subsequent ripening of the norsethite led to the evolution toward isotopic equilibrium of the system by slower exchange with a longer reaction time (i.e., slow dissolution-reprecipitation). Moreover, our first-principles calculation results indicate that the equilibrium isotope fractionation was approached, but not attained, even after 276 days of recrystallization at temperatures below 70 °C. In short, this study has identified two different types of dissolution-reprecipitation process during the carbonate mineral growth and highlights the importance of understanding formation mechanism and post-depositional history of carbonate in interpreting the isotopic data of carbonate minerals. [ABSTRACT FROM AUTHOR]

Microglia are neuroglia in the brain with an innate immune function and participate in the progress of neurodegenerative diseases. Osthole (OST) is a coumarin derivative extracted from Cnidium monnieri and bears a microglia-antagonizing ability. However, the underlying mechanism of the antagonism is not clear. The lipopolysaccharides-induced microglial BV2 cell line and amyloid-overexpressing fruit fly were used as models to study OST treatment. We found that OST treatment is sufficient to evoke NRF2 cascade under an LPS-induced inflammatory environment, and silencing NRF2 is sufficient to abolish the process. Moreover, we found that OST is sufficient to antagonize microglial activation in both LPS-induced BV2 cells and Aβ-overexpressing fruit flies, and silencing NRF2 abolishes OST's antagonism. Furthermore, OST treatment rescued survival, climbing, and the learning ability of Aβ-overexpressing fruit flies and relieved oxidative stress. In conclusion, we proved that OST antagonizes microglial activation induced by either LPS or Aβ and that NRF2 is necessary for OST's antagonism. [ABSTRACT FROM AUTHOR]

Numerous nanocarriers have been developed to deliver drugs for the treatment of hepatocellular carcinoma. However, the lack of specific targeting ability, the low administration efficiency, and insufficient absorption by hepatocellular carcinoma cells, severely limits the therapeutic effect of the current drugs. Therefore, it is still of great clinical significance to develop highly efficient therapies with few side effects for the treatment of hepatocellular carcinoma. Herein, we developed a highly effective nanocarrier, cyclic RGD peptide-conjugated magnetic mesoporous nanoparticles (RGDSPIO@MSN NPs), to deliver the chemotherapeutic drug doxorubicin (DOX) to human hepatocellular carcinoma HepG2 cells, and further explored their synergistic apoptosis-promoting effects. The results showed that the prepared RGDSPIO@MSN NPs had good stability, biosafety and drug-loading capacity, and significantly improved the absorption of DOX by HepG2 cells, and that the RGDSPIO@MSN@DOX NPs could synergistically promote the apoptosis of HepG2 cells. Thus, this cyclic RGD peptide-modified magnetic mesoporous silicon therapeutic nanosystem can be regarded as a potentially effective strategy for the targeted treatment of hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI)-induced neuroinflammation is closely associated with poor outcomes and high mortality in affected patients, with unmet needs for effective clinical interventions. A series of causal and disseminating factors have been identified to cause TBI-induced neuroinflammation. Among these are cellular microvesicles released from injured cerebral cells, endothelial cells, and platelets. In previous studies, we have put forward that cellular microvesicles can be released from injured brains that induce consumptive coagulopathy. Extracellular mitochondria accounted for 55.2% of these microvesicles and induced a redox-dependent platelet procoagulant activity that contributes to traumatic brain injury–induced coagulopathy and inflammation. These lead to the hypothesis that metabolically active extracellular mitochondria contribute to the neuroinflammation in traumatic brain injury, independent of their procoagulant activity. Here, we found that these extracellular mitochondria induced polarization of microglial M1-type pro-inflammatory phenotype, aggravating neuroinflammation, and mediated cerebral edema in a ROS-dependent manner. In addition, the effect of ROS can be alleviated by ROS inhibitor N-ethylmaleimide (NEM) in vitro experiments. These results revealed a novel pro-inflammatory activity of extracellular mitochondria that may contribute to traumatic brain injury–associated neuroinflammation. [ABSTRACT FROM AUTHOR]

Although seismic and hydrothermal data show evidence of magma–seawater interaction in slow spreading-rate ridges, such a process has been rarely observed in situ in lower oceanic crust. In this study, we reported petrological and mineral data on the plutonic rocks from the lower oceanic crust of the Lagkorco ophiolite from central Tibet, which shows geological and petrological features indicative of a slow-spreading ridge origin. Both troctolites and gabbros were derived from depleted magmas containing 0.5–1.0 wt.% H2O. Petrology and geochemistry indicate that troctolites have experienced two stages of melt impregnation: (1) early, water-poor melt impregnation in a dunitic matrix and (2) late, hydrous melt impregnation in a troctolitic matrix. Stage (1) generated oikocrysts of clinopyroxene and plagioclase within an olivine-rich matrix, while stage (2) formed brown amphibole. The high Cl (up to 0.25 wt%) contents of the brown amphibole and the fast cooling of the troctolites (~ 0.1 °C/year) suggest that stage (2) melt impregnation was associated with the hydration of the intercumulus melts by seawater infiltration. Together with the strong arc affinities of basalts, we suggest that Lagkorco ophiolite was formed at a nascent, slow-spreading back-arc basin with a fault-controlled crustal accretion. The deep-rooted faults may provide the channels for the downward seawater infiltration into the hot, impregnation zone near the crust–mantle transition zone. This study provides an example of seawater–magma interaction in the nascent back-arc lower oceanic crust with implications for the interplay among tectonic, hydrothermal, and magmatic processes at the slow-spreading ridges. [ABSTRACT FROM AUTHOR]

Local chronicles are a kind of historical record in China that are written in detail and play an important role in the transmission of local history and culture. Due to the single-text-carrier form of local chronicles, people have limited access to information on urban characteristics and culture; therefore, based on the cultural gene theory and Hofstede model, also known as the cultural onion model, this paper develops a "Spirit–Sign" content framework with the themes of urban characteristics and culture. Based on this framework, we map the urban characteristics and culture (visualization strategy and map design) of local chronicles. Taking the historic city of Dengfeng in the Central Plains as an example, the spatial information of the four historical city characteristics of Dengfeng was mined for the map design using the content framework of the city characteristics proposed in this study. The results of the study found that (1) there is a certain overlap in the spatial distribution of the four characteristic cultures of Dengfeng, indicating that the spiritual (traditional customs and famous people and events) and material (famous buildings and products) are complementary and mutually reinforcing to a certain extent; and (2) with the iterative development of Chinese dynasties, the material characteristic cultures of Dengfeng show strong temporal and spatial differences, which laterally reflect the changes in human activities and urban changes of each dynasty and also reflect the very important historical position occupied by Dengfeng in China. Compared with the traditional text-carrier form of local chronicles, the content construction and map visualization of the city's historical and cultural information proposed in this study can effectively explore more potential cultural characteristics, as well as spatial and temporal connections of Dengfeng and thus help people better understand the historical characteristics of the city. [ABSTRACT FROM AUTHOR]

INTRODUCTION: In patients with compensated advanced chronic liver disease (cACLD), the invasive measurement of hepatic venous pressure gradient is the best predictor of hepatic decompensation. This study aimed at developing an alternative risk prediction model to provide a decompensation risk assessment in cACLD. METHODS: Patients with cACLD were retrospectively included from 9 international centers within the Portal Hypertension Alliance in China (CHESS) network. Baseline variables from a Japanese cohort of 197 patients with cACLD were examined and fitted a Cox hazard regression model to develop a specific score for predicting hepatic decompensation. The novel score was validated in an external cohort (n = 770) from 5 centers in China, Singapore, Korea, and Egypt, and was further assessed for the ability of predicting clinically significant portal hypertension in a hepatic venous pressure gradient cohort (n = 285). RESULTS: In the derivation cohort, independent predictors of hepatic decompensation were identified including Stiffness of liver, Albumin, Varices, and platElets and fitted to develop the novel score, termed "SAVE" score. This score performed significantly better (all P < 0.05) than other assessed methods with a time-dependent receiver operating characteristic curve of 0.89 (95% confidence interval [CI]: 0.83–0.94) and 0.83 (95% CI: 0.73–0.92) in the derivation and validation cohorts, respectively. The decompensation risk was best stratified by the cutoff values at −6 and −4.5. The 5-year cumulative incidences of decompensation were 0%, 24.9%, and 69.0% in the low-risk, middle-risk, and high-risk groups, respectively (P < 0.001). The SAVE score also accurately predicted clinically significant portal hypertension (AUC, 0.85 95% CI: 0.80–0.90). DISCUSSION: The SAVE score can be readily incorporated into clinical practice to accurately predict the individual risk of hepatic decompensation in cACLD. [ABSTRACT FROM AUTHOR]

This article addresses the event‐triggered stabilization for large‐scale interconnected systems in presence of time delays. Two types of event‐triggering mechanisms (static event‐triggering mechanism and dynamic event‐triggering mechanism) are constructed. For each case, event‐triggered predictor‐based controller is designed to compensate time delays by using backstepping method. Via Lyapunov approach, constructive exponential stability conditions are established in the framework of linear matrix inequalities (LMIs). A numerical simulation example is given to demonstrate the effectiveness of the proposed methods. [ABSTRACT FROM AUTHOR]

For a topological space X, let CL(X) be the set of all non-empty closed subset of X, and denote the set CL(X) with the Vietoris topology by (C L (X) , V) . In this paper, we mainly discuss the hyperspace (C L (X) , V) when X is an infinite countable discrete space. As an application, we first prove that the hyperspace with the Vietoris topology on an infinite countable discrete space contains a closed copy of nth power of Sorgenfrey line for each n ∈ N . Then we investigate the tightness of the hyperspace (C L (X) , V) and prove that the tightness of (C L (X) , V) is equal to the set-tightness of X. Moreover, we extend some results about the generalized metric properties on the hyperspace (C L (X) , V) . Finally, we give a characterization of X such that (C L (X) , V) is a γ -space. [ABSTRACT FROM AUTHOR]

In recent years, climate change and the intervention of anthropogenic activities have altered the seasonal features of Asian dust storms. This may also cause seasonal variations (including dust occurrence frequency and optical/microphysical properties) in dust aerosols transported to downstream regions. The Jianghan Plain is dramatically influenced by multiple dust sources due to its geographical location in central China. In this study, we focused on the climatology of dust aerosols over the Jianghan Plain based on the 15-year (2006–2021) continuous space-borne observations of the Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) as well as Modern-Era Retrospective Analysis for Research and Applications version 2 (MERRA-2) reanalysis data. A typical dust event that intrudes the Jianghan Plain was studied in detail. According to the statistical results, dust aerosols frequently intrude into the Jianghan Plain in spring and winter, with occurrence frequencies (under cloud free condition hereafter) exceeding 0.70 and higher altitudes of 4–6 km. The dust occurrence frequency declined to approximately 0.40 in autumn and nearly zero in summer, while the dust plumes were generally located at lower altitudes of 1–3 km. The dust plumes observed in the Jianghan Plain were simultaneously linked to the Taklimakan Desert and Gobi Desert in spring and mainly originated from the Taklimakan Desert in winter and autumn. The dust particles were mainly distributed below 4-km altitude, with the largest dust extinction coefficients and dust mass concentrations in spring. In all seasons, the particle depolarization ratios are 0.1–0.2 below 4-km altitude, suggesting a possible mix with local anthropogenic aerosols. The mean dust column mass concentrations in spring showed an evident declining trend from 210 µg m−2 in 2006 to 100 µg m−2 in 2021 in the Jianghan Plain, attributed to the reduced dust activity in the source regions of Asian dust. [ABSTRACT FROM AUTHOR]

Background: Imidacloprid (IMD) is a widely used neonicotinoid-targeting insect nicotine acetylcholine receptors (nAChRs). However, off-target effects raise environmental concerns, including the IMD's impairment of the memory of honeybees and rodents. Although the down-regulation of inotropic glutamate receptor (iGluR) was proposed as the cause, whether IMD directly manipulates the activation or inhibition of iGluR is unknown. Using electrophysiological recording on fruit fly neuromuscular junction (NMJ), we found that IMD of 0.125 and 12.5 mg/L did not activate glutamate receptors nor inhibit the glutamate-triggered depolarization of the glutamatergic synapse. However, chronic IMD treatment attenuated short-term facilitation (STF) of NMJ by more than 20%. Moreover, by behavioral assays, we found that IMD desensitized the fruit flies' response to mechanosensitive, nociceptive, and photogenic stimuli. Finally, the treatment of the antioxidant osthole rescued the chronic IMD-induced phenotypes. We clarified that IMD is neither agonist nor antagonist of glutamate receptors, but chronic treatment with environmental-relevant concentrations impairs glutamatergic plasticity of the NMJ of fruit flies and interferes with the sensory response by mediating oxidative stress. [ABSTRACT FROM AUTHOR]

Both felsic and mafic intrusions occur in mantle peridotites of the New Caledonia ophiolite (Peridotite Nappe) and record important information regarding the magmatic evolution during subduction initiation. A systematic petrological, geochronological and geochemical study on gabbro/diorite samples from the Peridotite Nappe is performed to explore their petrogenesis. The gabbro is mainly composed of plagioclase, clinopyroxene and amphibole. Most clinopyroxene have been altered to hornblende or actinolite, whereas some amphibole with high Al2O3 (>8 wt%) and low SiO2 (<46 wt%) contents are of a magmatic origin. This suggests that the gabbro crystallized from hydrous melts. The gabbro shows depleted Sr-Nd-Hf isotope compositions, suggesting that the parental magma of the gabbro could have been derived from the depleted MORB-type mantle (DMM) asthenosphere. The gabbro zircon have δ18O values of +4.74-+6.63‰, which are slightly higher than the mantle-like δ18O values of +5.3 ± 0.6‰, indicating the involvement of subduction-related fluids in their genesis. The diorite mainly consists of albite (An1-4) and tremolite. The felsic dikes within the New Caledonia ophiolite, including granitoids, high-Mg felsic dikes and diorites, are oceanic plagiogranites. Extremely low TiO2 contents, roughly negative correlation of Yb and SiO2 contents, REE patterns of plagiogranites and mafic rocks, and compositions of zircon suggest that the plagiogranites were not products of fractional crystallization of MORB but were generated by hydrous melting of mafic protoliths. The diorite zircon show core-rim textures. Both rims and cores yield identical U-Pb ages of 54.6 ± 0.9 Ma vs 54.6 ± 0.6 Ma, and no old inherited cores were identified based on significantly older dates. Our studies show zircon U-Pb ages of ~55 Ma for the gabbro/diorite and titanite U-Pb age of ~53 Ma for the gabbro, which are older than the New Caledonia CE-boninites (51–47 Ma). Therefore, the magmatic evolution of the New Caledonia ophiolite during subduction initiation has been reconstructed. [ABSTRACT FROM AUTHOR]

As compared with cigarette smoking, use of Swedish snus is associated with significantly fewer health risks. Nicotine pouches (NPs), a new form of oral nicotine product, are smokeless and tobacco-free, comprising a nicotine-containing cellulose matrix inside a fiber pouch. NPs are similar in appearance/use to snus, but without tobacco, have the potential to further reduce tobacco-related harm. This study aimed to evaluate toxicant levels of NPs to estimate their position on the tobacco/nicotine product continuums of toxicant delivery and risk. NPs, snus and nicotine replacement therapy products (NRTs) were analyzed for 24–26 compounds applicable to oral tobacco, and their levels were compared. Twenty of these compounds were further used to compare the toxicant profile of NPs, as well as estimated daily toxicant exposure from NP use, with that of tobacco/nicotine products spanning the risk continuum. Of the compounds measured, 22 (NPs), 22 (lozenge NRT), 20 (gum NRT), and 11 (snus) were not quantifiable. Compared with snus, NPs had lower levels of 10 HPHCs and comparable/undetectable levels of a further 13. Across the product categories, NPs and NRTs had the lowest toxicant profiles and estimations of relative toxicant exposure. Based on the present chemical analysis and estimated exposure, use of NPs appears likely to expose users to lower levels of toxic compounds than Swedish snus, which is recognized to offer reduced levels of harm than associated with tobacco smoking. We conclude that NPs should be placed close to NRTs on the tobacco/nicotine product toxicant delivery continuum, although further studies will be needed to confirm this. [ABSTRACT FROM AUTHOR]

The development of high-efficiency flame-retardant polymers with low toxic fumes during combustion remains a great challenge. In this work, molybdenum trioxide (MoO3) was loaded on titanium carbide (Ti3C2Tx) nanosheets through electrostatic interactions for preparing a Ti3C2Tx–MoO3 hybrid. Then solvent mixing and melt blending methods were conducted to prepare flame-retardant thermoplastic polyurethane (TPU) nanocomposites. The scanning electron microscopy (SEM) result showed that the uniformly distributed Ti3C2Tx–MoO3 hybrid had a strong adhesion and good compatibility with the TPU matrix. The thermal stability of TPU was significantly improved upon the introduction of Ti3C2Tx–MoO3. The cone results revealed that the peak of heat release rate and the peak of smoke production rate of TPU nanocomposites containing 2.0 wt% Ti3C2Tx–MoO3 were significantly reduced by 26.2% and 42.9%, respectively, as compared to those of pure TPU. Besides, the peak of the carbon monoxide production rate and the total carbon monoxide yield of Ti3C2Tx–MoO3-2.0 were reduced by 44.7% and 44.7%, respectively. The distinguished fire resistance of the TPU/Ti3C2Tx–MoO3 system is principally attributed to the physical barrier effect and the catalytic carbonization of Ti3C2Tx–MoO3 hybrids together with the chemical conversion of Ti3C2Tx. [ABSTRACT FROM AUTHOR]

In recent years, much research has found that dysregulation of glutarylation is associated with many human diseases, such as diabetes, cancer, and glutaric aciduria type I. Therefore, glutarylation identification and characterization are essential tasks for determining modification-specific proteomics. This study aims to propose a novel deep neural network framework based on word embedding techniques for glutarylation sites prediction. Multiple deep neural network models are implemented to evaluate the performance of glutarylation sites prediction. Furthermore, an extensive experimental comparison of word embedding techniques is conducted to utilize the most efficient method for improving protein sequence data representation. The results suggest that the proposed deep neural networks not only improve protein sequence representation but also work effectively in glutarylation sites prediction by obtaining a higher accuracy and confidence rate compared to the previous work. Moreover, embedding techniques were proven to be more productive than the pre-trained word embedding techniques for glutarylation sequence representation. Our proposed method has significantly outperformed all traditional performance metrics compared to the advanced integrated vector support, with accuracy, specificity, sensitivity, and correlation coefficient of 0.79, 0.89, 0.59, and 0.51, respectively. It shows the potential to detect new glutarylation sites and uncover the relationships between glutarylation and well-known lysine modification. [ABSTRACT FROM AUTHOR]