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In this paper, we investigate the existence and uniqueness of the S-asymptotically ω -periodic mild solutions to a class of multi-term time-fractional measure differential equations with nonlocal conditions in an ordered Banach spaces. Firstly, we look for suitable concept of S-asymptotically ω -periodic mild solution to our concern problem, by means of Laplace transform and (β , γ k) -resolvent family { S β , γ k (t) } t ≥ 0 . Secondly, we construct monotone iterative method in the presence of the lower and upper solutions to the delayed fractional measure differential equations, and obtain the existence of maximal and minimal S-asymptotically ω -periodic mild solutions for the mentioned system. Finally, as the application of abstract results, an example is given to illustrate our main results. [ABSTRACT FROM AUTHOR]

Data-driven garment animation is a current topic of interest in the computer graphics industry. Existing approaches generally establish the mapping between a single human pose or a temporal pose sequence, and garment deformation, but it is difficult to quickly generate diverse clothed human animations. We address this problem with a method to automatically synthesize dressed human animations with temporal consistency from a specified human motion label. At the heart of our method is a two-stage strategy. Specifically, we first learn a latent space encoding the sequence-level distribution of human motions utilizing a transformer-based conditional variational autoencoder (Transformer-CVAE). Then a garment simulator synthesizes dynamic garment shapes using a transformer encoder–decoder architecture. Since the learned latent space comes from varied human motions, our method can generate a variety of styles of motions given a specific motion label. By means of a novel beginning of sequence (BOS) learning strategy and a self-supervised refinement procedure, our garment simulator is capable of efficiently synthesizing garment deformation sequences corresponding to the generated human motions while maintaining temporal and spatial consistency. We verify our ideas experimentally. This is the first generative model that directly dresses human animation. [ABSTRACT FROM AUTHOR]

Background: Data on the long-term oncological outcomes of patients who undergo conversion surgery (CS) in gastric cancer (GC) patients with peritoneal metastasis (PM) are limited. Methods: GC patients with PM who received intraperitoneal (ip) and systemic chemotherapy between April 2015 and January 2021 were enrolled. Multivariate analysis was performed to identify risk factors associated with survival. Clinicopathological and survival outcomes were compared between those with CS and those without CS (NCS). The paclitaxel (PTX) plus tegafur–gimeracil–oteracil potassium capsules (S-1) (PS) + ip PTX and oxaliplatin plus S-1 (SOX) + ip PTX groups were matched in a 1:1 ratio using propensity score matching. Oncological and survival data were collected and analyzed. Results: A total of 540 patients who received ip chemotherapy via subcutaneous port and systemic chemotherapy were analyzed and 268 patients were enrolled, including 113 who underwent CS and 155 who did not. Overall survival (OS) were 27.0 months and 11.8 months in the CS and NCS groups (P < 0.0001), respectively. R0 resection was an independent prognostic factor for patients who underwent CS. The OS of patients with or without ovariectomy was 21.3 or 12.0 months (P < 0.0001). No difference of clinicopathological and survival outcomes was found between the PS + ip PTX and SOX + ip PTX groups. Conclusion: Conversion therapy is safe and adverse events were manageable. CS improves the survival of GC patients with PM after ip and systemic chemotherapy. R0 is an important prognostic factor. Furthermore, outcomes are comparable between the PS + ip PTX and SOX + ip PTX groups. [ABSTRACT FROM AUTHOR]

Baccaurea ramiflora Lour., an evergreen tree of the Baccaurea genus of the Phyllanthaceae family, is primarily distributed in South Asia, Southeast Asia, and southern China, including southern Yunnan Province. It is a wild or semi-cultivated tree species with ornamental, edible, and medicinal value, exhibiting significant development potential. In this study, we present the whole-genome sequencing of B. ramiflora, employing a combination of PacBio SMRT and Illumina HiSeq 2500 sequencing techniques. The assembled genome size was 975.8 Mb, with a contig N50 of 509.33 kb and the longest contig measuring 7.74 Mb. The genome comprises approximately 73.47% highly repetitive sequences, of which 52.1% are long terminal repeat–retrotransposon sequences. A total of 29,172 protein-coding genes were predicted, of which 25,980 (89.06%) have been annotated, Additionally, 3452 non-coding RNAs were identified. Comparative genomic analysis revealed a close relationship between B. ramiflora and the Euphorbiaceae family, with both being sister groups that diverged approximately 59.9 million years ago. During the evolutionary process, B. ramiflora exhibited positive selection in 278 candidate genes. Synonymous substitution rate and collinearity analysis demonstrated that B. ramiflora underwent a single ancient genome-wide triploidization event, without recent genome-wide duplication events. This high-quality B. ramiflora genome provides a valuable resource for basic research and tree improvement programs focusing on the Phyllanthaceae family. [ABSTRACT FROM AUTHOR]

The diagnosis of leukemic T-cell malignancies is often challenging, due to overlapping features with reactive T-cells and limitations of currently available T-cell clonality assays. Recently developed therapeutic antibodies specific for the mutually exclusive T-cell receptor constant β chain (TRBC)1 and TRBC2 isoforms provide a unique opportunity to assess for TRBC-restriction as a surrogate of clonality in the flow cytometric analysis of T-cell neoplasms. To demonstrate the diagnostic utility of this approach, we studied 164 clinical specimens with (60) or without (104) T-cell neoplasia, in addition to 39 blood samples from healthy donors. Dual TRBC1 and TRBC2 expression was studied within a comprehensive T-cell panel, in a fashion similar to the routine evaluation of kappa and lambda immunoglobulin light chains for the detection of clonal B-cells. Polytypic TRBC expression was demonstrated on total, CD4+ and CD8+ T-cells from all healthy donors; and by intracellular staining on benign T-cell precursors. All neoplastic T-cells were TRBC-restricted, except for 8 cases (13%) lacking TRBC expression. T-cell clones of uncertain significance were identified in 17 samples without T-cell malignancy (13%) and accounted for smaller subsets than neoplastic clones (median: 4.7 vs. 69% of lymphocytes, p < 0.0001). Single staining for TRBC1 produced spurious TRBC1-dim subsets in 24 clinical specimens (15%), all of which resolved with dual TRBC1/2 staining. Assessment of TRBC restriction by flow cytometry provides a rapid diagnostic method to detect clonal T-cells, and to accurately determine the targetable TRBC isoform expressed by T-cell malignancies. [ABSTRACT FROM AUTHOR]

Ketogenic diet (KD) alleviates refractory epilepsy and reduces seizures in children. However, the metabolic/cell biologic mechanisms by which the KD exerts its antiepileptic efficacy remain elusive. Herein, we report that KD-produced β-hydroxybutyric acid (BHB) augments brain gamma-aminobutyric acid (GABA) and the GABA/glutamate ratio to inhibit epilepsy. The KD ameliorated pentetrazol-induced epilepsy in mice. Mechanistically, KD-produced BHB, but not other ketone bodies, inhibited HDAC1/HDAC2, increased H3K27 acetylation, and transcriptionally upregulated SIRT4 and glutamate decarboxylase 1 (GAD1). BHB-induced SIRT4 de-carbamylated and inactivated glutamate dehydrogenase to preserve glutamate for GABA synthesis, and GAD1 upregulation increased mouse brain GABA/glutamate ratio to inhibit neuron excitation. BHB administration in mice inhibited epilepsy induced by pentetrazol. BHB-mediated relief of epilepsy required high GABA level and GABA/glutamate ratio. These results identified BHB as the major antiepileptic metabolite of the KD and suggested that BHB may serve as an alternative and less toxic antiepileptic agent than KD. [ABSTRACT FROM AUTHOR]

The given text is a study published in the Blood Cancer Journal that explores the phenomenon of lineage switch in leukemia, where cells change from one lineage to another. The study includes 33 cases of acute leukemia that underwent lineage switch and provides valuable insights into the clinicopathological features and genetic drivers of this event. The findings suggest that certain risk factors, such as specific genetic abnormalities and the presence of a previous chronic myeloid malignancy, may increase the likelihood of lineage switch. The study emphasizes the importance of early detection and potential benefits of early allogeneic stem cell transplant in these cases, while also highlighting the need for further research to develop preventive and therapeutic strategies. [Extracted from the article]

Structural biology efforts using cryogenic electron microscopy are frequently stifled by specimens adopting "preferred orientations" on grids, leading to anisotropic map resolution and impeding structure determination. Tilting the specimen stage during data collection is a generalizable solution but has historically led to substantial resolution attenuation. Here, we develop updated data collection and image processing workflows and demonstrate, using multiple specimens, that resolution attenuation is negligible or significantly reduced across tilt angles. Reconstructions with and without the stage tilted as high as 60° are virtually indistinguishable. These strategies allowed the reconstruction to 3 Å resolution of a bacterial RNA polymerase with preferred orientation, containing an unnatural nucleotide for studying novel base pair recognition. Furthermore, we present a quantitative framework that allows cryo-EM practitioners to define an optimal tilt angle during data acquisition. These results reinforce the utility of employing stage tilt for data collection and provide quantitative metrics to obtain isotropic maps. Here, the authors quantify the effect of cryo-EM data acquisition with stage-tilt on the global resolution of reconstructions and present a tool for predicting an optimal stage-tilt angle to ameliorate the effects of preferred specimen orientation. [ABSTRACT FROM AUTHOR]

Severe trauma could induce sepsis due to the loss of control of the infection, which may eventually lead to death. Accurate and timely diagnosis of sepsis with severe trauma remains challenging both for clinician and laboratory. Combinations of markers, as opposed to single ones, may improve diagnosis. We compared the diagnostic characteristics of routinely used biomarkers of sepsis alone and in combination, trying to define a biomarker panel to predict sepsis in severe patients. This prospective observational study included patients with severe trauma (Injury severity score, ISS = 16 or more) in the emergency intensive care unit (EICU) at a university hospital. Blood samples were collected and plasma levels of procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6) and serum amyloid A (SAA) were measured using commercial enzyme linked immunosorbent assay (ELISA) kits. A total of 100 patients were eligible for analysis. Of these, 52 were diagnosed with sepsis. CRP yielded the highest discriminative value followed by PCT. In multiple logistic regression, SAA, CRP, and PCT were found to be independent predictors of sepsis. Bioscore which was composed of SAA, CRP, and PCT was shown to be far superior to that of each individual biomarker taken individually. Therefore, compared with single markers, the biomarker panel of PCT, CRP, and SAA was more predictive of sepsis in severe polytrauma patients. [ABSTRACT FROM AUTHOR]

While originally designed for natural language processing tasks, the self-attention mechanism has recently taken various computer vision areas by storm. However, the 2D nature of images brings three challenges for applying self-attention in computer vision: (1) treating images as 1D sequences neglects their 2D structures; (2) the quadratic complexity is too expensive for high-resolution images; (3) it only captures spatial adaptability but ignores channel adaptability. In this paper, we propose a novel linear attention named large kernel attention (LKA) to enable self-adaptive and long-range correlations in self-attention while avoiding its shortcomings. Furthermore, we present a neural network based on LKA, namely Visual Attention Network (VAN). While extremely simple, VAN achieves comparable results with similar size convolutional neural networks (CNNs) and vision transformers (ViTs) in various tasks, including image classification, object detection, semantic segmentation, panoptic segmentation, pose estimation, etc. For example, VAN-B6 achieves 87.8% accuracy on ImageNet benchmark, and sets new state-of-the-art performance (58.2 PQ) for panoptic segmentation. Besides, VAN-B2 surpasses Swin-T 4 mIoU (50.1 vs. 46.1) for semantic segmentation on ADE20K benchmark, 2.6 AP (48.8 vs. 46.2) for object detection on COCO dataset. It provides a novel method and a simple yet strong baseline for the community. The code is available at https://github.com/Visual-Attention-Network. [ABSTRACT FROM AUTHOR]

PPARα corepressor NCoR1 is a key regulator of fatty acid β-oxidation and ketogenesis. However, its regulatory mechanism is largely unknown. Here, we report that oncoprotein p21-activated kinase 4 (PAK4) is an NCoR1 kinase. Specifically, PAK4 phosphorylates NCoR1 at T1619/T2124, resulting in an increase in its nuclear localization and interaction with PPARα, thereby repressing the transcriptional activity of PPARα. We observe impaired ketogenesis and increases in PAK4 protein and NCoR1 phosphorylation levels in liver tissues of high fat diet-fed mice, NAFLD patients, and hepatocellular carcinoma patients. Forced overexpression of PAK4 in mice represses ketogenesis and thereby increases hepatic fat accumulation, whereas genetic ablation or pharmacological inhibition of PAK4 exhibites an opposite phenotype. Interestingly, PAK4 protein levels are significantly suppressed by fasting, largely through either cAMP/PKA- or Sirt1-mediated ubiquitination and proteasome degradation. In this way, our findings provide evidence for a PAK4-NCoR1/PPARα signaling pathway that regulates fatty acid β-oxidation and ketogenesis. PPARα corepressor NCoR1 is a key regulator of fatty acid β-oxidation and ketogenesis. Here, the authors demonstrate that p21-activated kinase 4 phosphorylates NCoR1 at T1619/T2124, resulting in PPARα transrepression and ketone body reduction. [ABSTRACT FROM AUTHOR]

Abstract The approval of bedaquiline has placed energy metabolism in the limelight as an attractive target space for tuberculosis antibiotic development. While bedaquiline inhibits the mycobacterial F1F0 ATP synthase, small molecules targeting other components of the oxidative phosphorylation pathway have been identified. Of particular interest is Telacebec (Q203), a phase 2 drug candidate inhibitor of the cytochrome bcc:aa3 terminal oxidase. A functional redundancy between the cytochrome bcc:aa3 and the cytochrome bd oxidase protects M. tuberculosis from Q203‐induced death, highlighting the attractiveness of the bd‐type terminal oxidase for drug development. Here, we employed a facile whole‐cell screen approach to identify the cytochrome bd inhibitor ND‐011992. Although ND‐011992 is ineffective on its own, it inhibits respiration and ATP homeostasis in combination with Q203. The drug combination was bactericidal against replicating and antibiotic‐tolerant, non‐replicating mycobacteria, and increased efficacy relative to that of a single drug in a mouse model. These findings suggest that a cytochrome bd oxidase inhibitor will add value to a drug combination targeting oxidative phosphorylation for tuberculosis treatment.

Background: Regarding trochanteric hip fractures, one type of posterior coronal fragments was described as the "banana-shaped fragment", while the impact of the banana-shaped fragment on mechanical stability has not been further studied. The current study investigated the association between the banana-shaped fragment and mechanical complications after surgery. Methods: This retrospective cohort study included 273 patients treated by proximal femoral nail antirotation (PFNA) in the full analysis. The age, the sex, the fracture side, the follow-up time, the American Society of Anesthesiologists classification, the operators, the fracture classification, the tip-apex distance, the blade positions, the reduction quality and the bone mineral density were analyzed in relation to mechanical complications, through univariate and multivariate approaches. Results: Mechanical complications happened in 33 patients. The banana-shaped fragment (adjusted odds ratio 5.240, 95% CI 2.172 to 12.641; p < 0.001), the tip-apex distance and the reduction quality showed significant association with mechanical complications in both univariate and multivariate analysis. Moreover, for 118 patients with the banana-shaped fragment, we found that the use of wire cerclage couldn't significantly lower the rates of mechanical complications (p = 0.648). Conclusions: The banana-shaped fragment had a negative impact on mechanical stability of trochanteric hip fractures treated by PFNA. In the perioperative period, the BSF should be carefully evaluated, and its specific handling deserves further study. [ABSTRACT FROM AUTHOR]

Immunity-related GTPase family M (IRGM), located on human chromosome 5q33.1, encodes a protein that promotes autophagy and suppresses the innate immune response. The minor allele of rs13361189 (−4299T>C), a single nucleotide polymorphism in the IRGM promoter, has been associated with several diseases, including Crohn's disease and tuberculosis. Although patterns of linkage disequilibrium and minor allele frequency for this polymorphism differ dramatically between subjects of European and African descent, studies of rs13361189 have predominantly been conducted in Europeans and the mechanism of association is poorly understood. We recruited a cohort of 68 individuals (30 White, 34 African American, 4 other race) with varying rs13361189 genotypes and assessed a panel of immune response measures including whole blood cytokine induction following ex vivo stimulation with Toll-like Receptor ligands. Minor allele carriers were found to have increased serum immunoglobulin M, C-reactive protein, and circulating CD8+ T cells. No differences in whole blood cytokines were observed between minor allele carriers and non-carriers in the overall study population; however, minor allele status was associated with increased induction of a subset of cytokines among African American subjects, and decreased induction among White subjects. These findings underline the importance of broad racial inclusion in genetic studies of immunity. [ABSTRACT FROM AUTHOR]

The films of Co1−xMnxFe2O4 (x = 0 − 0.4) were prepared on the substrates of Pt (111)/Ti/SiO2/Si by the sol-gel method. The effect of mole fraction of doping Mn ions on the microstructure, ferromagnetism and optic properties was investigated. The results show that, when x is less than 0.4, Mn ions have dissolved into the crystal lattices of CoFe2O4 without forming secondary phases. The surfaces of the films of Co1−xMnxFe2O4 possess polygonal and dense structures. The results of Raman show that Co2+ migrates from octahedral interstice to tetrahedral interstice when x is greater than 0.2. The results of XPS indicate that, in the Co0.8Mn0.2Fe2O4 film, Fe ions exist in the form of Fe2+ and Fe3+ and Mn ions exist in the form of Mn2+ and Mn3+. The results also show that, with increasing mole fraction of Mn ions, the values of saturation magnetization increase firstly, then decrease. When x is equal to 0.2, there is the maximum value of saturation magnetization (443.12 emu·cm−3). [ABSTRACT FROM AUTHOR]

Background: The prognosis of advanced gastric cancer (GC) invading the gastric serosa remains poor, mainly owing to high incidence of peritoneal recurrence. Patients with peritoneal metastases are often treated with neoadjuvant intraperitoneal and systemic chemotherapies (NIPS). Good responders to NIPS often undergo conversion gastrectomy. This study aims to explore biomarkers predicting the occurrence of peritoneal metastasis (PM) and evaluating the efficacy of NIPS in GC patients. Methods: We collected six peritoneal lavage (PL) samples from two patients with PM, two without PM, and two with diminished PM after NIPS via intraperitoneal access ports. We equally isolated microRNAs from exosomes derived from PL samples for deep sequencing. Two microRNAs (hsa-let-7g-3p and hsa-miR-10395-3p) were identified, and their expression levels were examined in PL samples of 99 GC patients using qRT-PCR. Moreover, we performed in vivo and in vitro functional assays to investigate effects of these microRNAs on metastasis and chemoresistance of GC cells. Results: Exosomal microRNA expression profiling of six PL samples indicated that the microRNA signature in exosomes of PLs from patients with diminished PM was similar to that from patients without PM. Expression levels of hsa-let-7g-3p and hsa-miR-10395-3p were associated with PM. In vivo and in vitro functional assays confirmed that hsa-let-7g-3p and hsa-miR-10395-3p are involved in GC metastasis and chemoresistance. Conclusion: PL-derived exosomes in GC contain large amounts of microRNAs related to PM. Moreover, hsa-let-7g-3p and hsa-miR-10395-3p could be used as biomarkers predicting PM and NIPS efficacy and are involved in GC metastasis and chemoresistance. [ABSTRACT FROM AUTHOR]

Directed differentiation of human pluripotent stem cells (hPSCs) into functional ureteric and collecting duct (CD) epithelia is essential to kidney regenerative medicine. Here we describe highly efficient, serum-free differentiation of hPSCs into ureteric bud (UB) organoids and functional CD cells. The hPSCs are first induced into pronephric progenitor cells at 90% efficiency and then aggregated into spheres with a molecular signature similar to the nephric duct. In a three-dimensional matrix, the spheres form UB organoids that exhibit branching morphogenesis similar to the fetal UB and correct distal tip localization of RET expression. Organoid-derived cells incorporate into the UB tips of the progenitor niche in chimeric fetal kidney explant culture. At later stages, the UB organoids differentiate into CD organoids, which contain >95% CD cell types as estimated by single-cell RNA sequencing. The CD epithelia demonstrate renal electrophysiologic functions, with ENaC-mediated vectorial sodium transport by principal cells and V-type ATPase proton pump activity by FOXI1-induced intercalated cells. Kidney collecting duct cells with physiologic functions are generated from human pluripotent stem cells. [ABSTRACT FROM AUTHOR]

In humans, a family of 25 bitter taste receptors (TAS2Rs) mediates bitter taste perception. A common approach to characterize bitter causative agents involves expressing TAS2Rs and the appropriate signal transducers in heterologous cell systems, and monitoring changes in the intracellular free calcium levels upon ligand exposure using a fluorescence-based modality, which typically suffers from a low signal window, and is susceptible to interference by autofluorescence, therefore prohibiting its application to screening of plant or food extracts, which are likely to contain autofluorescent compounds. The aim of this study is to develop and validate a bioluminescence-based intracellular calcium release assay for TAS2Rs that has a better assay performance than a fluorescence-based assay. Furthermore, the bioluminescence-based assay enabled the evaluation of TAS2R agonists within an autofluorescent matrix, highlighting its potential utility in the assessment of the bitterness-inducing properties of plant or food fractions by the food industry. Additionally, improvement to the bioluminescence-based assay for some TAS2Rs was achieved by altering their N-terminal signal sequences, leading to signal window enhancement. Altogether, the bioluminescence-based TAS2R assay can be used to perform functional studies of TAS2Rs, evaluate TAS2R-modulating properties of autofluorescent samples, and facilitate the discovery of compounds that can function as promising bitter taste modulators. [ABSTRACT FROM AUTHOR]

Land subsidence induced by groundwater level decline has spatiotemporal variations. Taking the Interferometric Synthetic Aperture Radar (InSAR) results and the groundwater subsidence data acquired by the monitoring stations as the source material, this paper aims to reveal the spatiotemporal heterogeneity of groundwater-land subsidence in Beijing plain by using the Wind Rose Map (WRM) method and the Change Point Analysis (CPA) method. The WRM results show that the amount and variation in subsidence differs in different directions. This method detected the formation of new subsidence centers and the slowdown of land subsidence in 2008. The CPA results show that obvious changes are detected in subsidence development at the Wangsiying (WSY), Tianzhu (TZ) and Wangjing (WJ) stations. However, there is a relatively stable trend of groundwater decline and land subsidence at the Tianzhu (TZ) station. The stages of land subsidence development show a significant response to groundwater. Moreover, changes in land subsidence also show delayed response behind the changes in groundwater level. The time-lag could be affected by the variation in amplitude of the groundwater level. [ABSTRACT FROM AUTHOR]

Humans can naturally and effectively find salient regions in complex scenes. Motivated by this observation, attention mechanisms were introduced into computer vision with the aim of imitating this aspect of the human visual system. Such an attention mechanism can be regarded as a dynamic weight adjustment process based on features of the input image. Attention mechanisms have achieved great success in many visual tasks, including image classification, object detection, semantic segmentation, video understanding, image generation, 3D vision, multimodal tasks, and self-supervised learning. In this survey, we provide a comprehensive review of various attention mechanisms in computer vision and categorize them according to approach, such as channel attention, spatial attention, temporal attention, and branch attention; a related repository https://github.com/MenghaoGuo/Awesome-Vision-Attentions is dedicated to collecting related work. We also suggest future directions for attention mechanism research. [ABSTRACT FROM AUTHOR]

Patients with chronic lymphocytic leukemia (CLL) with disease progression on ibrutinib have worse outcomes compared to patients stopping ibrutinib due to toxicity. A better understanding of expected outcomes in these patients is necessary to establish a benchmark for evaluating novel agents currently available and in development. We evaluated outcomes of 144 patients with CLL treated at Mayo Clinic with 2018 iwCLL disease progression on ibrutinib. The median overall survival (OS) for the entire cohort was 25.5 months; it was 29.8 months and 8.3 months among patients with CLL progression (n = 104) and Richter transformation (n = 38), respectively. Longer OS was observed among patients with CLL progression who had received ibrutinib in the frontline compared to relapsed/refractory setting (not reached versus 28.5 months; p = 0.04), but was similar amongst patients treated with 1, 2, or ≥3 prior lines (18.5, 30.9, and 26.0 months, respectively, p = 0.24). Among patients with CLL disease progression on ibrutinib, OS was significantly longer when next-line treatment was chimeric antigen receptor T-cell therapy (median not reached) or venetoclax-based treatment (median 29.8 months) compared to other approved treatments, such as chemoimmunotherapy, phosphoinositide 3'-kinase inhibitors, and anti-CD20 monoclonal antibodies (9.1 months; p = 0.03). These findings suggest an unmet need for this growing patient population. [ABSTRACT FROM AUTHOR]

Treated patients with multiple myeloma (MM) and PC leukemia (PCL) who were considered measurable residual disease (MRD) testing-eligible were identified and the proportion of patients in whom MRD testing was avoided by a positive PCPRO was calculated. The S-phase fraction of abnormal PCs was estimated by dividing the number of abnormal PCs in the S-window by the total number of abnormal PCs after manually gating G0-G1 and G2-M peaks [[7]]. B TO THE EDITOR: b Multiple myeloma (MM) is the second most common hematological malignancy in the United States predicted to cause 34,470 new cases and 12,640 deaths in 2022 [[1]]. [Extracted from the article]

Whether amino acids act on cellular insulin signaling remains unclear, given that increased circulating amino acid levels are associated with the onset of type 2 diabetes (T2D). Here, we report that phenylalanine modifies insulin receptor beta (IRβ) and inactivates insulin signaling and glucose uptake. Mice fed phenylalanine-rich chow or phenylalanine-producing aspartame or overexpressing human phenylalanyl-tRNA synthetase (hFARS) develop insulin resistance and T2D symptoms. Mechanistically, FARS phenylalanylate lysine 1057/1079 of IRβ (F-K1057/1079), inactivating IRβ and preventing insulin from promoting glucose uptake by cells. SIRT1 reverse F-K1057/1079 and counteract the insulin-inactivating effects of hFARS and phenylalanine. F-K1057/1079 and SIRT1 levels in white blood cells from T2D patients are positively and negatively correlated with T2D onset, respectively. Blocking F-K1057/1079 with phenylalaninol sensitizes insulin signaling and relieves T2D symptoms in hFARS-transgenic and db/db mice. These findings shed light on the activation of insulin signaling and T2D progression through inhibition of phenylalanylation. Whether amino acids act on cellular insulin signaling remains unclear. Here, the authors find that phenylalanine modifies insulin receptor beta (IRβ) and inactivates insulin signaling and glucose uptake and positively correlated with T2D onset. [ABSTRACT FROM AUTHOR]

In this work, carbon nanohorn (CNH)–decorated multi-walled carbon nanotube (MWCNT) (CNH@MWCNT) composite was prepared and used to modify glass carbon electrode (GCE) as sensitive electrochemical sensor for niclosamide (NA) determination. Herein, the decoration of CNHs induces higher dispersibility for MWCNTs, and endows the composite with better conductivity, larger surface area, and higher catalytic activity, which leads to significantly enhanced electrochemical behavior toward NA oxidation. The parameters such as mass ratios of CNHs and MWCHTs, the amount of composite materials, the accumulation time, and the solution pH are systematically optimized. Under optimized conditions, the developed electrochemical sensor exhibits a low detection limit of 2.0 nM with a wide linear range of 7.0 nM–10.0 µM and high anti-interference ability. In addition, the sensor displays good stability, repeatability, and reproducibility. The feasibility of the assay was verified by testing NA in brown rice and rice field water samples. [ABSTRACT FROM AUTHOR]

The Bi4−xErxTi3O12 films were deposited on the substrates via the spin-coating method. The doping of Er3+ does not give rise to the variation of phase composition and element valence state in the Bi4−xErxTi3O12 films. The Bi4−xErxTi3O12 films show dense surfaces and clear phase interfaces between the films and the substrates. And the surfaces of the Bi4−xErxTi3O12 films contain particles with various sizes and irregular shapes. The leakage current density and ferroelectricity of Er3+-doped Bi4Ti3O12 (Bi4−xErxTi3O12) are lower than those of Bi4Ti3O12 films. With increasing the doping concentration of Er3+, the values of leakage current density of Bi4−xErxTi3O12 films decrease at first and then increase. Meanwhile, the values of remanent polarization of Bi4−xErxTi3O12 films increase at the beginning and then decrease. Among the five films, the Bi3.4Er0.6Ti3O12 film exhibit smallest value of leakage current density (6.43 × 10−7 A·cm−2) and greatest value of remanent polarization (14.4 μC·cm−2), which indicates the better ferroelectric properties. This is beneficial for the application of ferroelectric functional devices. [ABSTRACT FROM AUTHOR]

The correct image for Figure 6i is: Graph The correct image for Figure 6j is: Graph These errors have been corrected in both the PDF and HTML versions of the Article. Correction to: I Nature Communications i https://doi.org/10.1038/s41467-023-40597-z, published online 17 August 2023 The original version of this Article contained incorrect images for the microscopy in Figure 6i and western blots in 6j. Author Correction: p21-activated kinase 4 suppresses fatty acid -oxidation and ketogenesis by phosphorylating NCoR1. [Extracted from the article]

Objective: To investigate the molecular characteristics in tumor immune microenvironment that affect long-term survival of patients with pancreatic adenocarcinoma (PAAD). Methods: The tumor related genetic features of a female PAAD patient (over 13-year survival) who suffered from multiple recurrences and metastases, and six operations over one decade were investigated deeply. Genomic features and immune microenvironment signatures of her primary lesion as well as six metastatic tumors at different time-points were characterized. Results: High-frequency clonal neoantigenic mutations identified in these specimens revealed the significant associations between clonal neoantigens with her prognosis after each surgery. Meanwhile, the TCGA and ICGC databases were employed to analyse the function of KRAS G12V in pancreatic cancer. Conclusions: The genomic analysis of clonal neoantigens combined with tumor immune microenvironment could promote the understandings of personalized prognostic evaluation and the stratification of resected PAAD individuals with better outcome. [ABSTRACT FROM AUTHOR]

Patients with large granular lymphocytic leukemia (LGLL) frequently present with neutropenia. When present, anemia is usually accompanied by neutropenia and/or thrombocytopenia and isolated anemia is uncommon. We evaluated a cohort of 244 LGLL patients spanning 15 years and herein report the clinicopathologic features of 34 (14%) with isolated anemia. The patients with isolated anemia showed a significantly male predominance (p = 0.001), a lower level of hemoglobulin (p < 0.0001) and higher MCV (p = 0.017) and were less likely to have rheumatoid arthritis (p = 0.023) compared to the remaining 210 patients. Of the 34 LGLL patients with isolated anemia, 13 (38%) presented with pure red cell aplasia (PRCA), markedly decreased reticulocyte count and erythroid precursors, and more transfusion-dependence when compared to non-PRCA patients. There was no other significant clinicopathologic difference between PRCA and non-PRCA patients. 32 patients were followed for a median duration of 51 months (6–199). 24 patients were treated (11/11 PRCA and 13/21 non-PRCA patients, p < 0.02). The overall response rate to first-line therapy was 83% [8/11 (72.7%) for PRCA, 12/13 (92.3%) for non-PRCA], including 14 showing complete response and 6 showing partial response with a median response duration of 48 months (12–129). Half of non-PRCA patients who were observed experienced progressive anemia. During follow-up, no patients developed neutropenia; however, 5/27 (18.5%) patients developed thrombocytopenia. No significant difference in overall survival was noted between PRCA and non-PRCA patients. In summary, this study demonstrates the unique features of LGLL with isolated anemia and underscores the importance of recognizing LGLL as a potential cause of isolated anemia, which may benefit from disease-specific treatment. LGLL patients with PRCA were more likely to require treatment but demonstrated similar clinicopathologic features, therapeutic responses, and overall survival compared to isolated anemia without PRCA, suggesting PRCA and non-PRCA of T-LGLL belong to a common disease spectrum. [ABSTRACT FROM AUTHOR]

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The distinction between chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) with isolated Hodgkin/Reed–Sternberg cells (CLL-HRS; background milieu with a paucity of inflammatory cells) and overt transformation to classic Hodgkin lymphoma (CLL-HL; mixed inflammatory background) is incompletely understood. This retrospective study examined the clinicopathologic features of CLL-HRS (n = 15) and CLL-HL (n = 31) patients seen over the past three decades from a single institution. The phenotypic features of Reed–Sternberg cells in both groups were similar, including expression of CD30, CD15, and PAX5, as well as EBV status. However, a spectrum of background CLL/SLL infiltration amongst the HRS cells was noted on pathologic review, and four patients had both diagnoses, either concurrently or in succession. The median overall survival (OS) of patients with CLL-HRS was 17.5 months compared to 33.5 months for patients with CLL-HL (P = 0.24). Among patients with CLL-HRS, those who received Hodgkin-directed therapy had a significantly longer median OS (57 months) compared to those who received CLL-directed therapy (8.4 months, P = 0.02). Our clinical and pathologic findings suggest a biologic continuum between CLL-HRS and CLL-HL and indicate that CLL-HRS patients may benefit from Hodgkin-directed therapy. [ABSTRACT FROM AUTHOR]

Mutations in SPOP E3 ligase gene are reportedly associated with genome-wide DNA hypermethylation in prostate cancer (PCa) although the underlying mechanisms remain elusive. Here, we demonstrate that SPOP binds and promotes polyubiquitination and degradation of histone methyltransferase and DNMT interactor GLP. SPOP mutation induces stabilization of GLP and its partner protein G9a and aberrant upregulation of global DNA hypermethylation in cultured PCa cells and primary PCa specimens. Genome-wide DNA methylome analysis shows that a subset of tumor suppressor genes (TSGs) including FOXO3, GATA5, and NDRG1, are hypermethylated and downregulated in SPOP-mutated PCa cells. DNA methylation inhibitor 5-azacytidine effectively reverses expression of the TSGs examined, inhibits SPOP-mutated PCa cell growth in vitro and in mice, and enhances docetaxel anti-cancer efficacy. Our findings reveal the GLP/G9a-DNMT module as a mediator of DNA hypermethylation in SPOP-mutated PCa. They suggest that SPOP mutation could be a biomarker for effective treatment of PCa with DNA methylation inhibitor alone or in combination with taxane chemotherapeutics. The molecular mechanism underlying the DNA hypermethylation phenotype observed in the SPOP-mutant prostate cancers is unclear. Here, the authors show that mutant SPOP induces global aberrant DNA methylation patterns through GLP/G9a and renders prostate cancer cells susceptible to DNA demethylating agents. [ABSTRACT FROM AUTHOR]

Intraspecific competition is a major force in mediating population dynamics, fuelling adaptation, and potentially leading to evolutionary diversification. Among the evolutionary arms races between parasites, one of the most fundamental and intriguing behavioural adaptations and counter-adaptations are superparasitism and superparasitism avoidance. However, the underlying mechanisms and ecological contexts of these phenomena remain underexplored. Here, we apply the Drosophila parasite Leptopilina boulardi as a study system and find that this solitary endoparasitic wasp provokes a host escape response for superparasitism avoidance. We combine multi-omics and in vivo functional studies to characterize a small set of RhoGAP domain-containing genes that mediate the parasite's manipulation of host escape behaviour by inducing reactive oxygen species in the host central nervous system. We further uncover an evolutionary scenario in which neofunctionalization and specialization gave rise to the novel role of RhoGAP domain in avoiding superparasitism, with an ancestral origin prior to the divergence between Leptopilina specialist and generalist species. Our study suggests that superparasitism avoidance is adaptive for a parasite and adds to our understanding of how the molecular manipulation of host behaviour has evolved in this system. Evolutionary arms races can drive adaptations in hosts and parasites as well as among competing parasites. A combination of multi-omics and functional tests identifies a set of genes that allow a parasitic wasp to minimize intraspecific competition by inducing hosts to escape before more wasps can parasitize them. [ABSTRACT FROM AUTHOR]

Lead-free films of Bi4-xNdxTi3O12 were deposited on Pt(111)/Ti/SiO2/Si(100) substrate via spin-coating methods. It is shown that there are no secondary phases in the films of Bi4-xNdxTi3O12 and clear interfaces between the films of Bi4-xNdxTi3O12 and substrates when the films are annealed at 700 °C. And the films of Bi4-xNdxTi3O12 also exhibit a blue light emission peak at 437 nm and a yellow light emission peak at 580 nm. There are narrower band gaps, greater values of dielectric constant and lower values of dielectric loss when the concentration of Nd3+ varies from 0 to 0.85. And the films of Bi4-xNdxTi3O12 possess the minimum of band gap energy (2.67 eV). Moreover, the films of Bi4-xNdxTi3O12 exhibit minimal leakage current density and maximal remanent polarization, which is highly beneficial for the potential applications in multi-functional devices. [ABSTRACT FROM AUTHOR]

Dysregulated extravillous trophoblast invasion and proliferation are known to increase the risk of recurrent spontaneous abortion (RSA); however, the underlying mechanism remains unclear. Herein, in our retrospective observational case-control study we show that villous samples from RSA patients, compared to healthy controls, display reduced succinate dehydrogenase complex iron sulfur subunit (SDHB) DNA methylation, elevated SDHB expression, and reduced succinate levels, indicating that low succinate levels correlate with RSA. Moreover, we find high succinate levels in early pregnant women are correlated with successful embryo implantation. SDHB promoter methylation recruited MBD1 and excluded c-Fos, inactivating SDHB expression and causing intracellular succinate accumulation which mimicked hypoxia in extravillous trophoblasts cell lines JEG3 and HTR8 via the PHD2-VHL-HIF-1α pathway; however, low succinate levels reversed this effect and increased the risk of abortion in mouse model. This study reveals that abnormal metabolite levels inhibit extravillous trophoblast function and highlights an approach for RSA intervention. Abnormal placentation is associated with recurrent spontaneous abortion (RSA) risk. Here the authors report that low embryonic villous succinate level associates with risk of RSA in patients, and increasing succinate levels is sufficient to reduce the incidence rate in a mouse model of spontaneous abortion. [ABSTRACT FROM AUTHOR]

The irregular domain and lack of ordering make it challenging to design deep neural networks for point cloud processing. This paper presents a novel framework named Point Cloud Transformer (PCT) for point cloud learning. PCT is based on Transformer, which achieves huge success in natural language processing and displays great potential in image processing. It is inherently permutation invariant for processing a sequence of points, making it well-suited for point cloud learning. To better capture local context within the point cloud, we enhance input embedding with the support of farthest point sampling and nearest neighbor search. Extensive experiments demonstrate that the PCT achieves the state-of-the-art performance on shape classification, part segmentation, semantic segmentation, and normal estimation tasks. [ABSTRACT FROM AUTHOR]

The films of (Bi0.5Na0.5)(Ti1-xMnx)O3-δ (BNTMx) were deposited on the substrates via the sol–gel method. The influence of the doping content of Mn on the microstructures and ferroelectric properties of the films were investigated. In addition, the valence states of Mn ions were analyzed. The results show that Mn ions have dissolved into the lattice of Bi0.5Na0.5TiO3 (BNT) without forming any secondary phase. When the doping content of Mn is 0.04, the film of BNTMx possesses a dense microstructure, maximum of remnant polarization (20.2 µC·cm−2), minimum value of leakage current density (3.31 × 10–5 A· cm−2), which shows good ferroelectric property and insulation performance. The results of XPS indicate that Mn ions exist in form of Mn2+, Mn3+ and Mn4+. The ratio of the amount of Mn4+ to that of Mn3+ and Mn2+ is 5.5:1. In this work, relationship between valence states of Mn ions and leakage current densities or ferroelectric property of the films were investigated in detail. The results will provide a new way for future applications of BNT-based multi-functional devices and an alternative for environmental-friendly ferroelectric materials. [ABSTRACT FROM AUTHOR]

We present a practical backend for stereo visual SLAM which can simultaneously discover individual rigid bodies and compute their motions in dynamic environments. While recent factor graph based state optimization algorithms have shown their ability to robustly solve SLAM problems by treating dynamic objects as outliers, their dynamic motions are rarely considered. In this paper, we exploit the consensus of 3D motions for landmarks extracted from the same rigid body for clustering, and to identify static and dynamic objects in a unified manner. Specifically, our algorithm builds a noise-aware motion affinity matrix from landmarks, and uses agglomerative clustering to distinguish rigid bodies. Using decoupled factor graph optimization to revise their shapes and trajectories, we obtain an iterative scheme to update both cluster assignments and motion estimation reciprocally. Evaluations on both synthetic scenes and KITTI demonstrate the capability of our approach, and further experiments considering online efficiency also show the effectiveness of our method for simultaneously tracking ego-motion and multiple objects. [ABSTRACT FROM AUTHOR]

Parasitoids are ubiquitous in natural ecosystems. Parasitic strategies are highly diverse among parasitoid species, yet their underlying genetic bases are poorly understood. Here, we focus on the divergent adaptation of a specialist and a generalist drosophilid parasitoids. We find that a novel protein (Lar) enables active immune suppression by lysing the host lymph glands, eventually leading to successful parasitism by the generalist. Meanwhile, another novel protein (Warm) contributes to a passive strategy by attaching the laid eggs to the gut and other organs of the host, leading to incomplete encapsulation and helping the specialist escape the host immune response. We find that these diverse parasitic strategies both originated from lateral gene transfer, followed with duplication and specialization, and that they might contribute to the shift in host ranges between parasitoids. Our results increase our understanding of how novel gene functions originate and how they contribute to host adaptation. Parasitism is a widespread evolutionary strategy. A study that spans functional and evolutionary genomics identifies the molecular basis and history underlying two genes that have mediated divergent parasitic strategies (specialist vs generalist) between two sister species of parasitoid wasp. [ABSTRACT FROM AUTHOR]

The silence of lncRNA small nucleolar RNA host gene 16 (SNHG16) suppressed acute lymphoblastic leukemia (ALL) cell proliferation and migration, whereas its role in acute myeloid leukemia (AML) still lacks clarity. This study showed that SNHG16 was upregulated in AML patients and cells. And SNHG16 overexpression remarkably enhanced the proliferation and migration capacities of HL60 and AML-193 cells, while SNHG16 knockdown acted the opposite way. Subsequently, we revealed that SNHG16 directly bound to CELF2 (CUGBP Elav-like family member 2) protein, and caused CELF2 mRNA unstably and proteins reducing. CELF2 was decreased both in AML patients and cells. CELF2 overexpression or interference weakened the effect of overexpressing or silencing SNHG16 on proliferation and migration. Moreover, the transfection of pcDNA-CELF2 elevated PTEN (phosphatase and tensin homolog) activity and hindered the phosphoinositide 3-kinase (PI3K)/AKT signaling. And SNHG16 reduced PTEN activity and promoted the PI3K/AKT pathway activation by restraining CELF2. Furthermore, GDC-0941 (a specific inhibitor of the PI3K/AKT pathway) impeded the effect of SNHG16 increase, and bpV(pic) (a specific PTEN inhibitor) declined the effect of SNHG16 decrease on cell proliferation and migration. Taken together, the present study indicated that SNHG16 promoted proliferation and migration of AML cells via PTEN/PI3K/AKT axis through suppressing CELF2 protein. [ABSTRACT FROM AUTHOR]

Recent studies have shown that long-term alcohol intake from food can lead to numerous mental disorders in humans, and the social and health effects of excessive intake of alcohol currently represent serious problems for governments and families worldwide. However, to date, it has not been determined how alcohol affects the hypothalamic–pituitary–adrenal (HPA) axis. The zebrafish offers a good model for studying the toxicology of food-grade ethanol. In the present study, using zebrafish larvae exposed to 1% ethanol, we performed zebrafish behavioral analysis. Samples were collected for enzyme-linked immunosorbent assay (ELISA) and quantitative real time-polymerase chain reaction (qRT-PCR) experiments, and statistical analysis was performed. We found that ethanol decreased the locomotor activity of zebrafish larvae, which showed a more intense reaction to external stimuli. Ethanol also increased the level of HPA axis hormones in zebrafish larvae, influenced the level of neurotransmitters, and altered the expression of key genes in neurotransmitter metabolism. Ethanol exposure affects zebrafish behavior, increases the level of HPA axis hormones in zebrafish larvae, affects the level of neurotransmitters, and affects the expression of key genes in dopamine and serotonin metabolism. These findings may help to elucidate the effects of ethanol on HPA axis activity. [ABSTRACT FROM AUTHOR]

The magnetoelectric composite films of Bi3.15Nd0.85Ti2.9Zr0.1O12 (BNTZO)–CoFe2O4 (CFO) were deposited on the substrates of Pt/Ti/SiO2/Si (111) by means of the sol–gel method. The results show that, in the composite films, there are tri-axial compressive stresses in the CFO films. Nevertheless, there are bi-axial tensile stresses and uniaxial compressive stress in the BNTZO films. The composite films possess compact microstructure and flat interface without forming intermediate layer. The composite films have good magnetoelectric properties besides both good ferroelectric and ferromagnetic properties. When Hdc is 738 Oe, the composite film of BNTZO-CFO possesses the maximum of αE, 114 mV cm−1 Oe−1, which is helpful for the application in multi-functional devices. [ABSTRACT FROM AUTHOR]

In this paper, we consider salient instance segmentation. As well as producing bounding boxes, our network also outputs high-quality instance-level segments as initial selections to indicate the regions of interest. Taking into account the category-independent property of each target, we design a single stage salient instance segmentation framework, with a novel segmentation branch. Our new branch regards not only local context inside each detection window but also the surrounding context, enabling us to distinguish instances in the same scope even with partial occlusion. Our network is end-to-end trainable and is fast (running at 40 fps for images with resolution 320 × 320). We evaluate our approach on a publicly available benchmark and show that it outperforms alternative solutions. We also provide a thorough analysis of our design choices to help readers better understand the function of each part of our network. Source code can be found at https://github.com/RuochenFan/S4Net. [ABSTRACT FROM AUTHOR]