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Abstract Accurate and efficient detection and segmentation of the urine formed element plays a vital role in the clinical diagnosis and treatment of many diseases, such as urinary system diseases, kidney diseases, and other diseases. However, artificial microscopy is subjective, and time- consuming. The mainstream detection and instance segmentation algorithms lack adequate accuracy and speed for the urine formed element due to small and dense targets. Therefore, this study proposes a quick one-stage urine formed element instance segmentation model based on YOLOv5n. The approach first employs a backbone architecture to extract features named shallow graphical features and semantic features from urine cells. Next, the neck network combines shallow graphical features with different deep semantic features, obtaining multi-scale, and multi-level features. Finally, according to these multi-level features, the head network of YOLOv5n integrates a small FCN network into the YOLOv5 detector. It obtains the location, classification, and segmentation results of the targets. To validate the superiority of this approach in terms of speed and accuracy, a special urine formed element dataset including 500 images was created. Experimental results show that the YOLOv5n method achieves a Mean Average Precision (mAP) at intersection over the union threshold of 0.5 (mAP50) with 91.8%, and Frames Per Second (FPS) of 63.3. Compared to Mask R-CNN and YOLOv8, its FPS increased by 62.6 and 60.9, respectively, resulting in nearly a hundred-fold speedup, and its mAP50 also increased by 3.6 and 1.4% points in accuracy, respectively. Additionally, the YOLOv5n obtains a superior balance of accuracy and speed in comparisons with SOLOv2, BoxInst, and ConvNeXt V2. This study developed a new automated analysis of urinary particles based on deep learning, and this method is expected to be used for the automated analysis and detection of the urine formed element. The experimental results also demonstrate that YOLOv5n can achieve more accurate and faster instance segmentation of urine formed element, providing technical support for clinical disease diagnosis.

Abstract Adamantinomatous craniopharyngioma (ACP) is a clinically aggressive tumor without effective treatment method. Previous studies proposed a paracrine tumorigenesis model, in which oncogenic β-catenin induces senescence in pituitary stem cells and the senescent cells lead the formation of paracrine tumors through secretion of pro-tumorigenic factors. However, there lacks characterization on senescent cells in ACPs. Here, we profiled 12 ACPs with single-cell RNA and TCR-sequencing to elucidate the cellular atlas in ACPs and 3 of them were also subject to spatial sequencing to localize different subpopulations of the tumor cells. In total, we obtained the transcriptome profiles of 70,682 cells. Tumor cells, which were unambiguously identified through the cellular mutation status of the driver CTNNB1 mutations, were clustered into 6 subsets. The whorl-like cluster (WC) cells show distinct molecular features from the other tumor cells and the palisading epithelium (PE) cells consists of a proliferating subset. Other than typical PE and WC, we identified two novel subpopulations of the tumor cells. In one subpopulation, the cells express a high level of cytokines, e.g., FDCSP and S100A8/A9, and are enriched with the senescence-associated secretory phenotype (SASP) factors. Hematoxylin and eosin staining reveals that these SASP cells lack an ordered structures and their nuclei are elongated. In the other subpopulation, the cell sizes are small and they are tightly packed together with an unusual high density expressing a high level of mitochondrial genes (median 10.9%). These cells are the origin of the tumor developmental trajectories revealed by RNA velocity and pseudo-time analysis. Single-cell RNA and TCR analysis reveals that some ACPs are infiltrated with clonally expanded cytotoxic T cells. We propose a hypothesis that WC and PE are formed via different negative regulation mechanisms of the overactivated WNT/β-catenin signaling which provides a new understanding on the tumorigenesis of ACPs. The study lays a foundation for future studies on targeting senescent cells in ACPs with senolytic compounds or other therapeutic agents.

Nanozymes exhibit immense potential and promising prospects in the realm of diagnostic imaging and tumor therapy, owing to their inherent physicochemical properties and enzymatic activities. With the further development and application of nanotechnology, nanozymes are expected to become an important tool in the field of medicine, providing new solutions for disease diagnosis and treatment. This review provides an overview of recent studies over the past five years on the application of nanozymes capable of responding to the tumor microenvironment (TME) in multimodal imaging, with a focus on hypoxia, acid pH, excess GSH and ROS. In addition, we present the current status of the development of several common multimodal imaging and related contrast agents, such as MRI/CT, MRI/PET, MRI/SPECT, PET/CT. Moreover, some thoughts on the challenges, future development, and clinical translation of tumor microenvironment-responsive nanozymes in the field of multimodal imaging are shared. This review aims to provide an up-to-date theranostic nanomedicine reference for those who focus on related fields, promote the progress of this interdisciplinary subject, and accelerate clinical translation.

Abstract As the new energy industry continues to progress, the health management of power batteries has become the key to ensuring the performance and safety of automobiles. Therefore, accurately predicting battery capacity decline is particularly important. A battery capacity degradation prediction model combining unscented particle filtering, particle swarm optimization, and SVR is constructed. It optimizes regression parameters through the introduced optimization strategy. Unscented particle filtering is used to improve particle swarm optimization and battery detection model. The study tested four various models of lithium-ion batteries. The model predicted a mean square error of 0.0011 for battery 5, 0.0007 for battery 6, 0.0022 for battery 7, and 0.0013 for battery 18. In the prediction of different battery types, the mean square error of the NIMH battery was reduced by 0.0008 compared with the particle swarm optimization-support vector regression algorithm, and by 0.0005 compared with the unscented particle filtering-regression vector regression algorithm. The mean square error of lithium-iron phosphate battery was reduced by 0.0008 and 0.0004 respectively compared with comparison models. The mean square error value of lithium titanate battery was reduced by 0.0007 and 0.0003 respectively in the research model compared with comparison models. It improves the prediction accuracy in lithium-ion batteries. Its application in battery health management can provide important technical support for improving battery performance and extending service cycles. The proposed method can be used for battery monitoring and management of power grid energy storage system. By accurately predicting the capacity decline of battery, the operation strategy of energy storage system can be optimized to ensure the efficient operation and long life of the system. The battery management system can be used for drones and aviation equipment to predict battery health and capacity decline in real time, ensuring the safety and reliability of flight missions.

Abstract. Background:. Adamantinomatous craniopharyngioma (ACP) is the commonest pediatric sellar tumor. No effective drug is available and interpatient heterogeneity is prominent. This study aimed to identify distinct molecular subgroups of ACP based on the multi-omics profiles, imaging findings, and histological features, in order to predict the response to anti-inflammatory treatment and immunotherapies. Methods:. Totally 142 Chinese cases diagnosed with craniopharyngiomas were profiled, including 119 ACPs and 23 papillary craniopharyngiomas. Whole-exome sequencing (151 tumors, including recurrent ones), RNA sequencing (84 tumors), and DNA methylome profiling (95 tumors) were performed. Consensus clustering and non-negative matrix factorization were used for subgrouping, and Cox regression were utilized for prognostic evaluation, respectively. Results:. Three distinct molecular subgroups were identified: WNT, ImA, and ImB. The WNT subgroup showed higher Wnt/β-catenin pathway activity, with a greater number of epithelial cells and more predominantly solid tumors. The ImA and ImB subgroups had activated inflammatory and interferon response pathways, with enhanced immune cell infiltration and more predominantly cystic tumors. Mitogen-activated protein kinases (MEK/MAPK) signaling was activated only in ImA samples, while IL-6 and epithelial–mesenchymal transition biomarkers were highly expressed in the ImB group, mostly consisting of children. The degree of astrogliosis was significantly elevated in the ImA group, with severe finger-like protrusions at the invasive front of the tumor. The molecular subgrouping was an independent prognostic factor, with the WNT group having longer event-free survival than ImB (Cox, P = 0.04). ImA/ImB cases were more likely to respond to immune checkpoint blockade (ICB) therapy than the WNT group (P

Abstract Purpose To investigate the influence of β-arrestin2 on the docetaxel resistance in castration-resistant prostate cancer (CRPC) and elucidate the underlying molecular mechanisms. Methods PC3 and DU145 cells with stable β-arrestin2 overexpression and C4-2 cells with stable β-arrestin2 knockdown, were constructed via using lentivirus and puromycin selection. MTT and colony formation assays were carried out to investigate the effect of β-arrestin2 expression on the docetaxel resistance of CRPC cells. Glycolysis analysis was used to assess the glycolytic capacity modulated by β-arrestin2. GO enrichment analysis, gene set enrichment analysis and Spearman correlation test were carried out to explore the potential biological function and mechanism via using public data from GEO and TCGA. The expressions of PKM2, Phospho-PKM2, Phospho-ERK1/2 and hnRNP A1 were detected by western blot. Functional blocking experiments were carried out to confirm the roles of PKM2 and hnRNP A1 in the regulation of β-arrestin2’s biological functions via silencing PKM2 or hnRNP A1 expression in cells with stable β-arrestin2 overexpression. Finally, nude mice xenograft models were established to confirm the experimental results of cell experiments. Results β-Arrestin2 significantly decreased the sensitivity of CRPC cells to docetaxel stimulation, through enhancing the phosphorylation and expression of PKM2. Additionally, β-arrestin2 increased PKM2 phosphorylation via the ERK1/2 signaling pathway and induced PKM2 expression in a post-transcriptional manner through an hnRNP A1-dependent PKM alternative splicing mechanism, rather than by inhibiting its ubiquitination degradation. Conclusion Our findings indicate that the β-arrestin2/hnRNP A1/PKM2 pathway could be a promising target for treating docetaxel-resistant CRPC.

Abstract Background ETS transcription factors, known as the E26 transformation-specific factors, assume a critical role in the regulation of various vital biological processes in animals, including cell differentiation, the cell cycle, and cell apoptosis. However, their characterization in mollusks is currently lacking. Results The current study focused on a comprehensive analysis of the ETS genes in blood clam Tegillarca granosa and other mollusk genomes. Our phylogenetic analysis revealed the absence of the SPI and ETV subfamilies in mollusks compared to humans. Additionally, several ETS genes in mollusks were found to lack the PNT domain, potentially resulting in a diminished ability of ETS proteins to bind target genes. Interestingly, the bivalve ETS1 genes exhibited significantly high expression levels during the multicellular proliferation stage and in gill tissues. Furthermore, qRT-PCR results showed that Tg-ETS-14 (ETS1) is upregulated in the high total hemocyte counts (THC) population of T. granosa, suggesting it plays a significant role in stimulating hemocyte proliferation. Conclusion Our study significantly contributes to the comprehension of the evolutionary aspects concerning the ETS gene family, while also providing valuable insights into its role in fostering hemocyte proliferation across mollusks.

The blood clam (Anadara granosa) is an economic bivalve that is relatively tolerant to hypoxia, but its molecular mechanism of hypoxia tolerance is unclear. We found that a significant decrease in extracellular Ca2+ concentration and a marked increase in intracellular Ca2+ concentration was observed in the blood clam through the fluorescence probe method, under hypoxic conditions at 0.5 mg/L. Concomitantly, there was a downward trend in the expression level of CaV2 mRNA, whereas NFAT (nuclear factor of activated T cells) expression increased by qRT-PCR. These findings suggest that the elevated intracellular Ca2+ concentration may activate negative transcription factors of NFAT, which subsequently suppresses the transcription of CaV2, leading to its decreased expression. Then, the NFAT RNA interference experiments supported this hypothesis. Sequence analysis and 3D structure prediction revealed conserved and mutated residue sites in blood clam compared to other bivalves. Hypoxia-induced changes in intracellular and extracellular Ca2+ concentrations, activating transcription factor NFAT and suppressing CaV2 expression. This study highlights the key roles of CaV2 and NFAT in hypoxia adaptation, paving the way for further exploration of hypoxia tolerance mechanisms in mollusca.

TTMV::RARA is a recently reported fusion gene associated with acute promyelocytic leukemia (APL), caused by the integration of torque teno mini virus (TTMV) genomic fragments into the second intron of the RARA gene. Currently, there have been only six documented cases, with clinical presentations showing significant variability. Although initial responses to all-trans retinoic acid (ATRA) treatment may be observed in patients with TTMV::RARA-APL, the overall prognosis remains unfavorable among infrequent reported cases. This article presents a pediatric case that manifested as PML::RARA-negative APL with central nervous system involvement at onset. The patient experienced both intramedullary and extramedullary relapse one year after undergoing allogeneic hematopoietic stem cell transplantation. Upon identification as TTMV::RARA-APL and subsequent administration of two rounds of ATRA-based treatment, the patient rapidly developed multiple RARA ligand-binding domain mutations and demonstrated extensive resistance to ATRA and various other therapeutic interventions. Additionally, the patient experienced ARID1A mutant clone expansion and progressed MYC-targeted gene activation. This case represents the first documentation of extramedullary involvement at both the initial diagnosis and relapse stages, emphasizing the intricate clinical features and challenges associated with the rapid accumulation of multiple ATRA-resistant mutations in TTMV::RARA-APL, characterizing it as a distinct and complex sub-entity of atypical APL.

Pig behavioral analysis based on multi-object tracking (MOT) technology of surveillance videos is vital for precision livestock farming. To address the challenges posed by uneven lighting scenes and irregular pig movements in the MOT task, we proposed a pig MOT method named RpTrack. Firstly, RpTrack addresses the issue of lost tracking caused by irregular pig movements by using an appropriate Kalman Filter and improved trajectory management. Then, RpTrack utilizes BIoU for the second matching strategy to alleviate the influence of missed detections on the tracking performance. Finally, the method utilizes post-processing on the tracking results to generate behavioral statistics and activity trajectories for each pig. The experimental results under conditions of uneven lighting and irregular pig movements show that RpTrack significantly outperforms four other state-of-the-art MOT methods, including SORT, OC-SORT, ByteTrack, and Bot-SORT, on both public and private datasets. The experimental results demonstrate that RpTrack not only has the best tracking performance but also has high-speed processing capabilities. In conclusion, RpTrack effectively addresses the challenges of uneven scene lighting and irregular pig movements, enabling accurate pig tracking and monitoring of different behaviors, such as eating, standing, and lying. This research supports the advancement and application of intelligent pig farming.

Abstract Background Radiotherapy is a commonly used tool in clinical practice to treat solid tumors. However, due to the unique microenvironment inside the tumor, such as high levels of GSH, overexpressed H2O2 and hypoxia, these factors can seriously affect the effectiveness of radiotherapy. Results Therefore, to further improve the efficiency of radiotherapy, a core–shell nanocomposite CeO2–MnO2 is designed as a novel radiosensitizer that can modulate the tumor microenvironment (TME) and thus improve the efficacy of radiation therapy. CeO2–MnO2 can act as a radiosensitizer to enhance X-ray absorption at the tumor site while triggering the response behavior associated with the tumor microenvironment. According to in vivo and in vitro experiments, the nanoparticles aggravate the killing effect on tumor cells by generating large amounts of ROS and disrupting the redox balance. In this process, the outer layer of MnO2 reacts with GSH and H2O2 in the tumor microenvironment to generate ROS and release oxygen, thus alleviating the hypoxic condition in the tumor area. Meanwhile, the manganese ions produced by degradation can enhance T1-weighted magnetic resonance imaging (MRI). In addition, CeO2–MnO2, due to its high atomic number oxide CeO2, releases a large number of electrons under the effect of radiotherapy, which further reacts with intracellular molecules to produce reactive oxygen species and enhances the killing effect on tumor cells, thus having the effect of radiotherapy sensitization. In conclusion, the nanomaterial CeO2–MnO2, as a novel radiosensitizer, greatly improves the efficiency of cancer radiation therapy by improving the lack of oxygen in tumor and responding to the tumor microenvironment, providing an effective strategy for the construction of nanosystem with radiosensitizing function. Conclusion In conclusion, the nanomaterial CeO2–MnO2, as a novel radiosensitizer, greatly improves the efficiency of cancer radiation therapy by improving the lack of oxygen in tumor and responding to the tumor microenvironment, providing an effective strategy for the construction of nanosystems with radiosensitizing function.

In this present paper, the optimization of microwave extraction (ME) of Cremastra appendiculata (D. Don) Makino was performed using the single factor design and response surface methodology. The ME extraction yield along with the contents of three major components of C. appendiculata Makino, including militarine, dactylorhin A, and colchicine was selected as the comprehensive indicators to evaluate the extraction process. Subsequently, the HPLC fingerprint of the above three components from 13 batches of C. appendiculata Makino was investigated. Finally, the anti-fungal activity of C. appendiculata Makino extract was evaluated by conducting a disk-diffusion method. The results demonstrated that the optimal ME technologies of C. appendiculata Makino were the ethanol concentration of 55%, the solid-liquid ratio of 1:30 g/mL, and the extraction time of 17 min. Under the above conditions, the extract yield was 12.83%. HPLC fingerprint analysis results showed that the contents of three major components displayed a consistent trend in all 13 tested samples. Militarine was found existed in 13 batches of C. appendiculata Makino, while dactylorhin A and colchicine were not detected in one sample. The results indicated a content difference in three active ingredients in C. appendiculata Makino from different areas. The anti-phytopathogenic activity results showed that the C. appendiculata Makino extract did not shown inhibitory activity against Colletotrichum gloeosporioides, Phytophthora capsica, Botrytis cinerea, Alternaria solani, Pseudomonas fluorescens, Xanthomnas oryzae, and Fusarium graminearum with their inhibition zones were less than 6 mm. However, the C. appendiculata Makino extract exhibited inhibitory activity toward to Ralstonia solanacearum with the diameter of the inhibition zone was 8.5 mm, showed antibacterial selectivity. In this study, the optimal ME technologies of C. appendiculata Makino was determined, and the established method the contents of three major components of C. appendiculata Makino was stable and feasible.These results can provide the basis for the quality control and comprehen-sive utilization of C. appendiculata Makinos.

Abstract The molecular biological differences between cyst walls and those in solid bodies are the foundation of the outcomes. In this study, the CTNNB1 mutations were confirmed by DNAsequencing; CTNNB1 expression levels were detected by PCR; the differences between solid bodies and cyst walls in proliferative capacity and tumor stem cell niches were assessed by immunohistochemistry; the effect of the residual cyst wall on recurrence was assessed by follow-up. Mutations in the CTNNB1 in the cyst wall and the solid body were identical in each case. No differences were found in the transcriptional level of CTNNB1 between the cyst walls and the solid bodies (P = 0.7619). The cyst wall showed a pathological structure similar to the solid body. Proliferative capacity of cyst walls was stronger than that of solid body (P = 0.0021), and β-catenin nuclear positive cells (cell clusters) in cyst walls were more than that in solid tumor (P = 0.0002). The retrospective 45 ACPs showed residual cyst wall was significantly associated with tumor recurrence or regrowth (P = 0.0176). Kaplan–Meier analysis showed there was a significant difference in the prognosis between GTR and STR (P

In this paper, we mainly study connections between ideals of the semisimple EMV-algebra M and filters on some nonempty set Ω. We show that there is a bijection between the set of all closed ideals of M and the set of all filters on Ω. We prove that the topological space of all closed prime ideals of M and the topological space of all weak ultrafilters on Ω are homeomorphic.

Abstract Oxidative stress damage to renal epithelial cells is the main pathological factor of calcium oxalate calculi formation. The development of medicine that could alleviate oxidative damage has become the key to the prevention and treatment of urolithiasis. Herein, porous nanorods CeO2 nanoparticles (CNPs) were selected from CeO2 with different morphologies as an antioxidant reagent to suppress kidney calcium oxalate crystal depositions with excellent oxidation resistance due to its larger specific surface area. The reversible transformation from Ce3+ to Ce4+ could catalyze the decomposition of excess free radicals and act as a biological antioxidant enzyme basing on its strong ability to scavenge free radicals. The protection capability of CNPS against oxalate-induced damage and the effect of CNPS on calcium oxalate crystallization were studied. CNPS could effectively reduce reactive oxygen species production, restore mitochondrial membrane potential polarity, recover cell cycle progression, reduce cell death, and inhibit the formation of calcium oxalate crystals on the cell surface in vitro. The results of high-throughput sequencing of mRNA showed that CNPs could protect renal epithelial cells from oxidative stress damage caused by high oxalate by suppressing the expression gene of cell surface adhesion proteins. In addition, CNPS can significantly reduce the pathological damage of renal tubules and inhibit the deposition of calcium oxalate crystals in rat kidneys while having no significant side effect on other organs and physiological indicators in vivo. Our results provide a new strategy for CNPS as a potential for clinical prevention of crystalline kidney injury and crystal deposition.

Abstract The clinical characteristics of persistent postural-perceptual dizziness (PPPD) vary according to patient age and inducing factors. We aimed to analyze the differences in the clinical characteristics of PPPD with different patient age groups and different etiologies. A total of 122 PPPD patients hospitalized in the vertigo ward of Nanjing Brain Hospital from December 2018 to July 2021 were enrolled. According to whether dizziness symptoms were secondary to organic diseases, PPPD patients were divided into the primary (p-) and secondary (s-) PPPD groups; subgroups were created according to age including youth group, middle-aged group, older adults group 1 and older adults 2. We collected detailed data from each patients, including scores on the Dizziness Handicap Inventory (DHI), mental state and other clinical data. The ratio of males to females was 1:2. The prevalence of emotional disorders in the middle-aged group was the highest (67.57%) and that in the older adults groups was lower (48.08% in older adults group 1 and 8.70% in older adults group 2, P = 0.000). The proportion of p-PPPD patients with emotional disorders was significantly higher than that of s-PPPD patients (53.48% vs. 30.56%, P = 0.028). The average total DHI score in the middle-aged group was significantly higher than that in older adults group 2 (52.86 vs. 35.04, P = 0.032), and the Beck anxiety score in the middle-aged group was higher than that in older adults group 2 (38.89 vs. 27.65, P = 0.000). The middle-aged group had the highest proportion of women, the highest proportion of patients with emotional disorders and the highest vertigo score. The proportion of patients with emotional disorders and the vertigo scores were lower in the older adults groups.

Road space rationing policies reduced traffic volume by half in Beijing during the 2008 Olympic Games, which in turn decreased the mean surface temperature by up to 2.4 °C, according to statistical analysis of remotely sensed thermal observations.

The modulation transfer function (MTF) serves as a crucial technical index for assessing the imaging quality of remote sensing cameras, which is integral throughout their entire operational cycle. Currently, the MTF evaluation of remote sensing cameras primarily relies on the slanted-edge method. The factors influencing the slanted-edge method’s effectiveness are broadly classified into two categories: algorithmic factors and image factors. This paper innovatively comprehensively analyzes the influencing factors of the slanted-edge method and proposes an improved slanted-edge method to calculate the MTF testing method of remote sensing cameras, which is applied to the MTF testing of remote sensing cameras. Since the traditional algorithm can only be applied in the small angle situation, this paper proposes a new method of slanted-edge method test calculation based on the optimal oversampling rate (OSR) adaptive model of the slanted edge and uses simulation experiments to verify the reliability of the algorithm model through the deviation of the slanted-edge angle calculation and MTF measurement, and the results show that the algorithm improves the accuracy of the MTF measurement compared with the ISO-cos and OMINI-sine methods. Then, the effects of the slanted-edge angle, image region of interest (ROI), as well as image contrast and signal-to-noise ratio (SNR) on the accuracy of the MTF calculation by the slanted-edge method were quantitatively analyzed as the constraints of the slanted-edge method test. Based on the laboratory target experiment, the algorithm flow and various influencing factors obtained in the simulation stage are verified, and the experimental results are more consistent with the various test results obtained in the simulation stage. Consequently, the slanted-edge method introduced in this paper is applicable for future remote sensing camera MTF testing. This approach offers a valuable reference for on-orbit focusing, satellite operational condition monitoring, lifespan estimation, and image restoration.

In this paper, we introduce a new algebraic structure called extended quasi-MV algebras, which are generalizations of quasi-MV algebras. The notions of ideals, ideal congruences and filters in Equasi-MV algebras were introduced and their mutual relationships were investigated. There is a bijection between the set of all ideals and the set of all ideal congruences on an Equasi-MV algebra.

In this manuscript, we report torque teno mini virus (TTMV) as a cause of acute promyelocytic leukemia (APL) lacking PML::RARA in a 3-year-old boy. Astolfi et al. firstly identified partial integration of the TTMV genome into RARA intron 2, which resulted in in-frame TTMV::RARA fusion in two APL-like pediatric cases without PML::RARA in November 2021. This fascinating report identified an unexpected exogenous genetic cause of APL and could be of great importance for diagnosing and managing APL. Here we report the third childhood APL-like case caused by TTMV integration and investigate the location and structure of the integrated TTMV sequence. These findings suggest TTMV::RARA is a recurrent cause of APL lacking PML::RARA. Considering the widespread prevalence of TTMV in the population, more TTMV::RARA positive APL-like cases might remain to be identified. Establishing a bioinformatic analysis strategy optimized for the highly variable TTMV genome sequence may facilitate the identification of TTMV::RARA by whole transcript sequencing. An effective PCR protocol to identify TTMV::RARA based on a profound analysis of the conservation of TTMV segments in the fusion transcript is also expected. Also, further investigation is needed to elucidate the oncogenic mechanisms of TTMV integration and the clinical features of TTMV::RARA positive patients.

Abstract Limited studies have been described DEAD‐box helicase 41 (DDX41) mutations in hematological diseases other than myeloid neoplasms. In this study, DDX41 mutations were identified in 0.8% of myeloid neoplasms, 0.9% of acute lymphoblastic leukemia (ALL), and 1.0% of aplastic anemia (AA). A total of 15 causal DDX41 variants in 14 patients were detected; seven of which have not been reported previously. In myeloid neoplasms, the median age of patients with germline missense was lower than that of germline nonsense mutations. In ALL, the characteristics of DDX41 mutation were distinct. This study first reported DDX41 mutations in ALL and AA, expanding its mutation and phenotypic spectrum.

Abstract Background The design of stable and biocompatible black phosphorus-based theranostic agents with high photothermal conversion efficiency and clear mechanism to realize MRI-guided precision photothermal therapy (PTT) is imminent. Results Herein, black phosphorus nanosheets (BPs) covalently with mono-dispersed and superparamagnetic ferrous selenide (FeSe2) to construct heteronanostructure nanoparticles modified with methoxy poly (Ethylene Glycol) (mPEG-NH2) to obtain good water solubility for MRI-guided photothermal tumor therapy is successfully designed. The mechanism reveals that the enhanced photothermal conversion achieved by BPs-FeSe2-PEG heteronanostructure is attributed to the effective separation of photoinduced carriers. Besides, through the formation of the P-Se bond, the oxidation degree of FeSe2 is weakened. The lone pair electrons on the surface of BPs are occupied, which reduces the exposure of lone pair electrons in air, leading to excellent stability of BPs-FeSe2-PEG. Furthermore, the BPs-FeSe2-PEG heteronanostructure could realize enhanced T2-weighted imaging due to the aggregation of FeSe2 on BPs and the formation of hydrogen bonds, thus providing accurate PTT guidance and generating hyperthermia to inhabit tumor growth under NIR laser with negligible toxicity in vivo. Conclusions Collectively, this work offers an opportunity for fabricating BPs-based heteronanostructure nanomaterials that could simultaneously enhance photothermal conversion efficiency and photostability to realize MRI-guided cancer therapy. Graphic abstract

Abstract Fusion genes (FGs) are important genetic abnormalities in acute leukemias, but their variety and occurrence in acute leukemias remain to be systematically described. Whole transcriptome sequencing (WTS) provides a powerful tool for analyzing FGs. Here we report the FG map revealed by WTS in a consecutive cohort of 1000 acute leukemia cases in a single center, including 539 acute myeloid leukemia (AML), 437 acute lymphoblastic leukemia (ALL), and 24 mixed-phenotype acute leukemia (MPAL) patients. Bioinformatic analysis identified 792 high-confidence in-frame fusion events (296 distinct fusions) which were classified into four tiers. Tier A (pathogenic), B (likely pathogenic), and C (uncertain significance) FGs were identified in 61.8% cases of the total cohort (59.7% in AML, 64.5% in ALL, and 63.6% in MPAL). FGs involving protein kinase, transcription factor, and epigenetic genes were detected in 10.7%, 48.5%, and 15.1% cases, respectively. A considerable amount of novel FGs (82 in AML, 88 in B-ALL, 13 in T-ALL, and 9 in MPAL) was identified. This comprehensively described real map of FGs in acute leukemia revealed multiple FGs with clinical relevance that have not been previously recognized. WTS is a valuable tool and should be widely used in the routine diagnostic workup of acute leukemia.

Immunotherapy assays using immunoadjuvants and tumor antigens could greatly increase the survival rates of patients with malignant tumors. As effective carriers, metal-organic frameworks (MOFs) have been widely utilized in cancer therapy due to their remarkable histocompatibility and low toxicity. Herein, we constructed a multimodal imaging-guided synergistic cancer photoimmunotherapy by employing a specific MOF (MIL101-NH2) as the core carrier; the MOF was dual-dressed with photoacoustic and fluorescent signal donors (indocyanine green, ICG) and immune adjuvants (cytosine-phosphate-guanine sequence, CpG) and named ICG-CpG@MOF. This nanocarrier could passively target the tumor site through the EPR effect and achieve multimodal imaging (fluorescence, photoacoustic, photothermal and magnetic resonance imaging) of the tumor. Synergistic cancer photoimmunotherapy was achieved via simultaneous photodynamic and photothermal methods with 808 nm laser irradiation. ICG-CpG@MOF achieved the GSH-controlled release of immunoadjuvant into the tumor microenvironment. Furthermore, the released tumor-associated antigen along with CpG could induce the transformation of tumor cells from cold to hot by activating the immune system, which significantly enhanced tumor cytotoxicity and achieved high cure rates with minimal side-effects. This strategy utilizing multimodal imaging and synergistic cancer photoimmunotherapy provides a promising approach for the diagnosis and treatment of cancer.

Objective Renal sympathetic denervation (RDN) is an alternative treatment for resistant hypertension (RH). This study aims to compare ablation effects using three radiofrequency applicators (i.e., balloon-based four electrodes, spiral and monopolar devices). Methods An idealized three-dimensional model of the renal artery was established using COMSOL Multiphysics to mimic radiofrequency ablation (RFA). Radiofrequency (RF) energy was delivered to the tissue at the same simulation settings, i.e., 4, 6, and 8 W for 60 s, using the three abovementioned RF applicators. The temperature distribution in the tissue was calculated using the coupled electrical–thermal–fluid finite element method. Lesion borders were defined using 50 °C isotherms. The maximum lesion depth, width, area, and circumferential coverage rate were compared among the three applicators at a blood flow of 0.4 m/s. Monopolar RF ablations in a renal artery phantom model were performed to validate the reliability of the simulation method. Results The balloon-based system yields greater lesion depths and widths compared with spiral and monopolar denervation under the same power. The range of maximum lesion depth is 1.58–3.11 mm for balloon-based RDN, 0.90–1.81 mm for spiral RDN and 1.12–2.38 mm for monopolar RDN, at a power of 4–8 W. The corresponding ranges of maximum lesion width are 2.22–5.73, 1.48–3.54, and 1.93–5.31 mm, respectively, and the circumferential coverage rates of the renal artery are 41.43%–91.99%, 31.71%–66.23%, and 9.55%–23.06%, respectively. The average velocity after balloon-based, spiral, and monopolar RDN increases by 3, 5, and 1 cm/s, respectively. The validation of the computer model offered prediction errors are

Abstract Background Fanconi anemia (FA) is the most common inherited bone marrow failure (BMF) syndrome with 22 related genes identified. The ALDH2 rs671variant has been proved related to accelerate the progression of BMF in FA patients. The phenotype and genetic basis of Chinese FA patients have not been investigated yet. Methods We analyzed the 22 FA-related genes of 63 BMF patients suspected to be FA. Clinical manifestations, morphological and cytogenetic feathers, ALDH2 genotypes, treatment, and outcomes of the definite cases were retrospectively studied. Results A total of 21 patients were confirmed the diagnosis of FA with the median age of BMF onset was 4-year-old. The number of patients manifested as congenital malformations and growth retardation were 20/21 and 14/21, respectively. BM dysplasia and cytogenetic abnormalities were found in 13/20 and 8/19 patients. All the patients with abnormal karyotypes also manifested as BM dysplasia or had evident blasts. Thirty-five different mutations were identified involving six genes and including twenty novel mutations. FANCA mutations contributed to 66.67% of cases. Eight patients harboring ALDH2-G/A genotype have a significantly younger age of BMF onset (p = 0.025). Within the 19 patients adhering to continuous follow-up, 15 patients underwent hematopoietic stem cell transplantations (HSCTs). During the 29 months of follow-up, 8/19 patients died, seven of which were HSCT-related, and one patient who did not receive HSCT died from severe infection. Conclusions The phenotypic and genetic spectrum of Chinese FA patients is broad. Bone marrow dysplasia and cytogenetic abnormalities are prevalent and highly consistent. The overall outcome of HSCTs is disappointing. Nationwide multicenter studies are needed for the rarity and adverse outcome of this disease.

Abstract Background Several models have been developed to predict asymptomatic carotid stenosis (ACS), however these models did not pay much attention to people with lower level of stenosis (

Unmanned aerial vehicle (UAV)-based snow depth is mapped as the difference between snow-on and snow-off digital surface models (DSMs), which are derived using the structure from motion (SfM) technique with ground control points (GCPs). In this study, we evaluated the impacts of the quality and deployment of GCPs on the accuracy of snow depth estimates. For 15 GCPs in our study area, we surveyed each of their coordinates using an ordinary global positioning system (GPS) and a differential GPS, producing two sets of GCP measurements (hereinafter, the low-accuracy and high-accuracy sets). The two sets of GCP measurements were then incorporated into SfM processing of UAV images by following two deployment strategies to create snow-off and snow-on DSMs and then to retrieve snow depth. In Strategy A, the same GCP measurements in each set were used to create both the snow-on and snow-off DSMs. In Strategy B, each set of GCP measurements was divided into two sub-groups, one sub-group for creating snow-on DSMs and the other sub-group for snow-off DSMs. The accuracy of snow depth estimates was evaluated in comparison to concurrent in-situ snow depth measurements. The results showed that Strategy A, using both the low-accuracy and high-accuracy sets, generated accurate snow depth estimates, while in Strategy B, only the high-accuracy set could generate reliable snow depth estimates. The results demonstrated that the deployment of GCPs had a significant influence on UAV-based SfM snow depth retrieval. When accurate GCP measurements cannot be guaranteed (e.g., in mountainous regions), Strategy A is the optimal option for producing reliable snow depth estimates. When highly accurate GCP measurements are available (e.g., collected by differential GPS in open space), both deployment strategies can produce accurate snow depth estimates.