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Abstract Background Stereotactic body radiation therapy (SBRT) has been widely used for pancreatic cancer. However, there is still a lack of studies comparing the latest SBRT techniques in terms of clinical efficacy and safety. Objectives: This study aims to evaluate three latest SBRT delivery platforms: CyberKnife (CK), Tomography Radixact (TOMO), and Halcyon volume rotation intensity modulation therapy (VMAT) for the treatment of pancreatic cancer. Methods Sixteen patients with pancreatic cancer treated with CK were retrospectively analyzed. SBRT plans were designed using Precision and Eclipse software. CK plans were optimized in two forms: fixed collimator (CK-Fixed) and multi-leaf grating collimator (CK-MLC). TOMO plans were designed with 2.5 cm Fixed Jaw, pitch 0.123–0.43 and 4.0 modulation factors in precision system. In Eclipse 15.6 system, photon optimizer (OP) algorithm was used to design the coplanar two-arc Halcyon VMAT. The median radiation dose was 40 Gy (35–45 Gy) in 5 fractions. The effectiveness of clinical treatment was evaluated by comparing the homogeneity index (HI), conformity index (CI), coverage of the planning target volume (PTV) and dose distribution parameters of organs at risk (OAR). Results All plans met the limits of clinical target dose and OAR. CK-MLC plans had the lowest maximum dose of 2 cm normal tissue from PTV margin (D2cm), indicating a low risk of peripheral radiation damage. Additionally, the CK-MLC plans had the lowest dose parameters and provided the best protection for the kidney, spinal cord, small intestine, and duodenum, with a paired t-test p

Abstract Time-optimal control holds promise across the full spectrum of quantum technologies, where the rapid generation of unitary gates and state transformations is crucial to mitigate decoherence effects. In practical scenarios, quantum systems are always immersed in an external time-dependent field or potential, either owing to the inevitable influence of the environment or as a sought-after effect for enhanced coherence. The challenge then lies in finding the time-optimal approach to navigate quantum systems amidst dynamical ambient Hamiltonians, a pursuit that has proven elusive thus far. We showcase the implementation of arbitrary quantum state transformations and a universal set of single-qubit gates under a background Landau-Zener Hamiltonian. Leveraging the favorable coherence properties of timedomain Rabi oscillations, we achieve velocities surpassing the Mandelstam-Tamm quantum speed limit and significantly lower energy costs than those incurred by conventional quantum control techniques. These findings highlight a promising pathway to expedite and economize high-fidelity quantum operations.

In order to solve the problem that random selection of clustering number k can easily lead to instability and low computational efficiency of k-means clustering algorithm in the zoning calculation of wind load on the surface of long-span roof structures, an improved Canopy-k-means clustering algorithm was proposed. Firstly, the Canopy algorithm was introduced, and the selection of its initial threshold and clustering center was improved to reduce the blindness of the initial value selection so as to improve the reliability of the results of wind load zoning. Secondly, the improved Canopy algorithm was used to preprocess the wind load dataset to determine the cluster number k quickly and accurately. Thirdly, the improved Canopy algorithm was combined with k-means to achieve the accurate identification of the optimal classification number k, so that the improved Canopy-k-means clustering algorithm can get the zoning results quickly and accurately when the wind load on the surface of long-span roof structure was divided. Finally, taking a long-span cylindrical roof dry coal shed structure as an example, based on the test results of the surface wind load data obtained from the wind tunnel test, the improved Canopy-k-means clustering algorithm was used to calculate the surface wind load. The results show that by using the improved Canopy-k-means clustering algorithm, the wind loads on the surface of long-span roofs at 0 °, 50 °and 90 °wind angles are divided into three different zones, and the corresponding SD values are 2.36,3.51 and 2.52,respectively, which are significantly lower than those obtained by the traditional k-means clustering algorithm, and the intra-class compactness and inter-class dispersion are obviously improved. Therefore, the improved Canopy-k-means clustering algorithm can obtain the optimal zoning results quickly and accurately, and has good engineering application value for wind load zoning on the surface of long-span roofs.

Abstract Moyamoya disease (MMD) suffers from impaired cerebrovascular hemodynamics and high perioperative complications occurrence. This study aims to propose and evaluate the relationship between intraoperative hemodynamics and perioperative complications, and propose a potential compensatory self-recirculation network in MMD. We prospectively enrolled 63 MMD patients undergone combined revascularization, and patients were divided into decreased and increased group according to decreased and increased microvascular transit time (MVTT), respectively. Mean age of all patients was 45.9 ± 9.4 years. The post-bypass hyperperfusion syndrome occurrence was significantly higher in the decreased MVTT group, and the cerebral infarction occurrence was significantly higher in the increased MVTT group. For the hemodynamics of the recipient artery around anastomosis, the parameters of distal site demonstrated a significant higher intensity and shorter time in the decreased MVTT group, while the parameters of the proximal site demonstrated a significant higher intensity and shorter time in the increased MVTT group. Pre-bypass and post-bypass collision of blood flow in artery and vein were firstly observed and illustrated. Intraoperative hemodynamics showed close relationship with perioperative complications. The blood flow of MMD seems to develop a unique compensatory self-recirculation system and contribute to the clinical complications, providing a new insight to the clinical management the pathology of the disease.

Abstract The aim of the study was to analyze and discuss the value of preoperative systemic immune inflammation index (SII) and prognostic nutritional index (PNI) in predicting the prognosis of patients with renal cell carcinoma (RCC) after operation, and to establish a nomogram prediction model for patients with RCC after operation based on SII and PNI. From January 2014 to December 2018, 210 patients with RCC who underwent surgical treatment at the Xuzhou Central Hospital were selected as the research object. The receiver operating characteristic curve (ROC) was used to determine the optimal cut-off value for preoperative SII, PNI, LMR, PLR, NLR and the patients were divided into groups according to the optimal cutoff values. The survival rate of patients was evaluated. The risk factors that affect the prognosis of patients with RCC were determined by LASSO and Cox regression analysis, and a prognostic nomogram was constructed based on this result. The bootstrap method was used for internal verification of the nomogram model. The prediction efficiency and discrimination of the nomogram model were evaluated by the calibration curve and index of concordance (C-index), respectively. The average overall survival (OS) of all patients was 75.385 months, and the 1-, 2-and 3-year survival rates were 95.5%, 86.6% and 77.2%, respectively. The survival curve showed that the 5-year OS rate of low SII group was significantly higher than that of high SII group (89.0% vs. 64.5%; P

Objective: To provide the mechanism-based pharmacotherapy of the Huatan Qushi formula (HTQS formula), for the health management and treatment of non-alcoholic fatty liver disease (NAFLD). Methods: A rat model of NAFLD was employed to examine the efficacy and safety of the HTQS formula. In vivo active components and potential mechanisms of the HTQS formula were identified using UPLC‒MS/MS combined with network pharmacology. The influence of the HTQS formula on the dominating proteins in PI3K/Akt pathway was validated in vivo using western blot. Finally, 16S rRNA sequencing of the gut microbiome was conducted followed by targeted metabolomics detecting fecal short-chain fatty acids (SCFAs) and bile acids to determine the impact of the HTQS formula on gut microbiota. Results: The HTQS formula reduced weight gain and hepatic steatosis in NAFLD rats and decreased serum total cholesterol (TC), triglycerides, blood glucose, and insulin resistance (IR) without causing liver or kidney injury. We detected 28 components using UPLC‒MS/MS and identified 439 shared targets between NAFLD and the HTQS formula. Primarily, we focused on the PI3K/Akt signaling pathway based on protein‒protein interaction network analysis. We validated that the HTQS formula inhibited liver steatosis and inflammation by increasing the phosphorylation levels of PI3K, AKT, P27, GSK3β in the PI3K/Akt signaling pathway. 16S rRNA sequencing revealed that the HTQS formula reduced the abundance of the genus Family_XIII_AD3011_group, which was positively correlated with IR and taurodeoxycholic acid. In addition, Lachnospiraceae_UCG_010 inversely correlated with TC and five bile acids, which could be essential to the therapeutic effect of the HTQS formula against NAFLD. Conclusions: The HTQS formula proved to be an effective pharmacotherapy for NAFLD without causing liver or kidney injury. Multiple potent components of the HTQS formula could alleviate liver steatosis and lipid metabolism disorder by modulating the PI3K/Akt signaling pathway and restoring gut microbiota composition.

Abstract Clear cell renal cell carcinoma (ccRCC) is characterized by Von Hippel Lindau (VHL) gene loss of function mutation, which leads to the accumulation of hypoxia-inducible factor 2α (HIF2α). HIF2α has been well-established as one of the major oncogenic drivers of ccRCC, however, its therapeutic targeting remains a challenge. Through an analysis of proteomic data from ccRCCs and adjacent non-tumor tissues, we herein revealed that Ubiquitin-Specific Peptidase 7 (USP7) was upregulated in tumor tissues, and its depletion by inhibitors or shRNAs caused significant suppression of tumor progression in vitro and in vivo. Mechanistically, USP7 expression is activated by the transcription factors FUBP1 and FUBP3, and it promotes tumor progression mainly by deubiquitinating and stabilizing HIF2α. Moreover, the combination of USP7 inhibitors and afatinib (an ERBB family inhibitor) coordinately induce cell death and tumor suppression. In mechanism, afatinib indirectly inhibits USP7 transcription and accelerates the degradation of HIF2α protein, and the combination of them caused a more profound suppression of HIF2α abundance. These findings reveal a FUBPs-USP7-HIF2α regulatory axis that underlies the progression of ccRCC and provides a rationale for therapeutic targeting of oncogenic HIF2α via combinational treatment of USP7 inhibitor and afatinib.

Abstract Moyamoya disease, characterized by basal cerebral artery obstruction, was studied for differential protein expression to elucidate its pathogenesis. Proteomic analysis of cerebrospinal fluid from 10 patients, categorized by postoperative angiography into good and poor prognosis groups, revealed 46 differentially expressed proteins. Notably, cadherin 18 (CDH18) was the most significantly upregulated in the good prognosis group. In addition, the expression of cadherin 18 (CDH18) and phenotypic transformation-related proteins were measured by qRT-PCR and western blot. The effects of CDH18 in vascular smooth muscle cells were detected by CCK-8, EdU, transwell and wound healing assays. The overexpression of CDH18 in vascular smooth muscle cells (VSMCs) was found to inhibit proliferation, migration, and phenotypic transformation. These findings suggest CDH18 as a potential therapeutic target in moyamoya disease.

[Objecttives] The influence of moisture in raw coal, particle size and coal bunker material on the fluidity of raw coal was studied to find out the main reasons for coal clogging in raw coal bunkers.MethodsA raw coal flowability experimental device was designed and built to conduct flowability experiments on raw coal with different moisture and particle sizes, and flow characteristics diagrams were drew to obtain the effects of various factors on raw coal flowability.ResultsThe greater the moisture in the raw coal, the more right the broken line in the flow characteristic diagram is, the less the falling mass, the worse the mobility, and the greater the rotation angle required for complete falling.The difference in the initial position of coal falling is due to the difference in static friction between different particle sizes, resulting in different repose angles. At the same time, the decrease in moisture will reduce the friction force and increase the falling mass. The liquidity bend line of polytetrafluoroethylene material is located at the front, and the friction coefficient at the bottom is small. At the same angle, the mass drops more and the mobility is enhanced.ConclusionsMoisture plays a key role in the fluidity of raw coal, the influence of particle size on the fluidity of raw coal is weak, and only the interaction with moisture can have a great influence on the fluidity of raw coal. Material also has a greater impact on the fluidity of raw coal, but when the moisture is low, the impact can be ignored.

Abstract It is accepted that cancer stem cells (CSCs) are key to the occurrence, progression, drug resistance, and recurrence of bladder cancer (BLCA). Here, we aimed to characterize the landscapes of CSCs and investigate the biological and clinical signatures based on a prognostic model constructed by genes associated with CSCs. The malignant epithelial cells were discovered and sorted into six clusters through single cell analysis. C2 was identified as the CSCs. The signaling involved in the interactions between C2, cancer-associated fibroblasts (CAFs), and immune cells mainly consisted of MK, THBS, ANGPTL, VISFATIN, JAM, and ncWNT pathways. The CSC-like prognostic index (CSCLPI) constructed by the random survival forest was a reliable risk factor for BLCA and had a stable and powerful effect on predicting the overall survival of patients with BLCA. The level of CAFs was higher among patients with higher CSCLPI scores, suggesting that CAFs play a significant role in regulating biological characteristics. The CSCLPI-developed survival prediction nomogram has the potential to be applied clinically to predict the 1-, 2-, 3-, and 5-year overall survival of patients with BLCA. The CSCLPI can be used for prognostic prediction and drug treatment evaluation in the clinic.

Abstract Flueggea virosa (Roxb. ex Willd.) Royle, an evergreen shrub and small tree in the Phyllanthaceae family, holds significant potential in garden landscaping and pharmacological applications. However, the lack of genomic data has hindered further scientific understanding of its horticultural and medicinal values. In this study, we have assembled a haplotype-resolved genome of F. virosa for the first time. The two haploid genomes, named haplotype A genome and haplotype B genome, are 487.33 Mb and 477.53 Mb in size, respectively, with contig N50 lengths of 31.45 Mb and 32.81 Mb. More than 99% of the assembled sequences were anchored to 13 pairs of pseudo-chromosomes. Furthermore, 21,587 and 21,533 protein-coding genes were predicted in haplotype A and haplotype B genomes, respectively. The availability of this chromosome-level genome fills the gap in genomic data for F. virosa and provides valuable resources for molecular studies of this species, supporting future research on speciation, functional genomics, and comparative genomics within the Phyllanthaceae family.

Abstract Dracaena cambodiana Pierre ex Gagn. (Asparagaceae) is the source plant of Dragon’s blood and has high ornamental values in gardening. Currently, this species is classified as the second-class state-protected species in the National Key Protected Wild Plants (NKPWP) of China. However, limited genomic data has hindered a more comprehensive scientific understanding of the processes involved in the production of Dragon’s blood and the related conservation genomics research. In this study, we assembled a haplotype-resolved genome of D. cambodiana. The haploid genomes, haplotype A and haplotype B, are 1,015.22 Mb and 1,003.13 Mb in size, respectively. The completeness of haplotype A and haplotype B genomes was 98.60% and 98.20%, respectively, using the “embryophyta_10” dataset. Haplotype A and haplotype B genomes contained 27,361 and 27,066 protein-coding genes, respectively, with nearly all being functionally annotated. These findings provide new insights into the genomic characteristics of D. cambodiana and will offer additional genomic resources for studying the biosynthesis mechanism of Dragon’s blood and the horticultural application of Dragon trees.

Abstract Spontaneous intracerebral hemorrhage (ICH) is a very serious kind of stroke. If the outcome of patients can be accurately assessed at the early stage of disease occurrence, it will be of great significance to the patients and clinical treatment. The present study was conducted to investigate whether non-contrast computer tomography (NCCT) models of hematoma and perihematomal tissues could improve the accuracy of short-term prognosis prediction in ICH patients with conservative treatment. In this retrospective analysis, a total of 166 ICH patients with conservative treatment during hospitalization were included. Patients were randomized into a training group (N = 132) and a validation group (N = 34) in a ratio of 8:2, and the functional outcome at 90 days after clinical treatment was assessed by the modified Rankin Scale (mRS). Radiomic features of hematoma and perihematomal tissues of 5 mm, 10 mm, 15 mm were extracted from NCCT images. Clinical factors were analyzed by univariate and multivariate logistic regression to identify independent predictive factors. In the validation group, the mean area under the ROC curve (AUC) of the hematoma was 0.830, the AUC of the perihematomal tissue within 5 mm, 10 mm, 15 mm was 0.792, 0.826, 0.774, respectively, and the AUC of the combined model of hematoma and perihematomal tissue within 10 mm was 0.795. The clinical-radiomics nomogram consisting of five independent predictors and radiomics score (Rad-score) of the hematoma model were used to assess 90-day functional outcome in ICH patients with conservative treatment. Our findings found that the hematoma model had better discriminative efficacy in evaluating the early prognosis of conservatively managed ICH patients. The visual clinical-radiomics nomogram provided a more intuitive individualized risk assessment for 90-day functional outcome in ICH patients with conservative treatment. The hematoma could remain the primary therapeutic target for conservatively managed ICH patients, emphasizing the need for future clinical focus on the biological significance of the hematoma itself.

Abstract Euglena gracilis (E. gracilis), pivotal in the study of photosynthesis, endosymbiosis, and chloroplast development, is also an industrial microalga for paramylon production. Despite its importance, E. gracilis genome exploration faces challenges due to its intricate nature. In this study, we achieved a chromosome-level de novo assembly (2.37 Gb) using Illumina, PacBio, Bionano, and Hi-C data. The assembly exhibited a contig N50 of 619 Kb and scaffold N50 of 1.12 Mb, indicating superior continuity. Approximately 99.83% of the genome was anchored to 46 chromosomes, revealing structural insights. Repetitive elements constituted 58.84% of the sequences. Functional annotations were assigned to 39,362 proteins, enhancing interpretative power. BUSCO analysis confirmed assembly completeness at 80.39%. This first high-quality E. gracilis genome offers insights for genetics and genomics studies, overcoming previous limitations. The impact extends to academic and industrial research, providing a foundational resource.

Abstract With the continuous expansion of saline soils under climate change, understanding the eco-evolutionary tradeoff between the microbial mitigation of carbon limitation and the maintenance of functional traits in saline soils represents a significant knowledge gap in predicting future soil health and ecological function. Through shotgun metagenomic sequencing of coastal soils along a salinity gradient, we show contrasting eco-evolutionary directions of soil bacteria and archaea that manifest in changes to genome size and the functional potential of the soil microbiome. In salt environments with high carbon requirements, bacteria exhibit reduced genome sizes associated with a depletion of metabolic genes, while archaea display larger genomes and enrichment of salt-resistance, metabolic, and carbon-acquisition genes. This suggests that bacteria conserve energy through genome streamlining when facing salt stress, while archaea invest in carbon-acquisition pathways to broaden their resource usage. These findings suggest divergent directions in eco-evolutionary adaptations to soil saline stress amongst microbial clades and serve as a foundation for understanding the response of soil microbiomes to escalating climate change.

Cyprinus acutidorsalis (Wang, 1979) is an endemic fish in China that is sparsely distributed in the Hainan provinces and Guangxi Zhuang Autonomous Region (GZAR). In this study, the complete mitochondrial genome of C. acutidorsalis from the Hainan population from the Wanquan River was sequenced, and its phylogenetic relationship was analyzed. The circular mtDNA was 16,581 bp in length, and the overall base composition was A (32.0%), C (27.5%), T (24.8%), and G (15.70%), with a slight bias toward A + T. The complete mitogenome encoded 13 protein-coding genes (PCGs), 22 tRNA genes, two rRNA genes, and a control region. Phylogenetic analysis indicated that the most closely related fish to C. acutidorsalis from the Hainan population was C. acutidorsalis from the Guangxi population. These findings offer basic molecular data and a better understanding of the phylogenetic relationships among the Cyprinus species.

Abstract Prunus conradinae, a valuable flowering cherry belonging to the Rosaceae family subgenus Cerasus and endemic to China, has high economic and ornamental value. However, a high-quality P. conradinae genome is unavailable, which hinders our understanding of its genetic relationships and phylogenesis, and ultimately, the possibility of mining of key genes for important traits. Herein, we have successfully assembled a chromosome-scale P. conradinae genome, identifying 31,134 protein-coding genes, with 98.22% of them functionally annotated. Furthermore, we determined that repetitive sequences constitute 46.23% of the genome. Structural variation detection revealed some syntenic regions, inversions, translocations, and duplications, highlighting the genetic diversity and complexity of Cerasus. Phylogenetic analysis demonstrated that P. conradinae is most closely related to P. campanulata, from which it diverged ~ 19.1 million years ago (Mya). P. avium diverged earlier than P. cerasus and P. conradinae. Similar to the other Prunus species, P. conradinae underwent a common whole-genome duplication event at ~ 138.60 Mya. Furthermore, 79 MADS-box members were identified in P. conradinae, accompanied by the expansion of the SHORT VEGETATIVE PHASE subfamily. Our findings shed light on the complex genetic relationships, and genome evolution of P. conradinae and will facilitate research on the molecular breeding and functions of key genes related to important horticultural and economic characteristics of subgenus Cerasus.

IntroductionCodonopsis pilosula is a significant plant in traditional Chinese medicine, valued for its edible and medicinal properties. However, the lack of available genomic resources has hindered further research.MethodsThis study presents the first chromosome-scale genome assembly of C. pilosula using PacBio CLR reads and Hi-C scaffolding technology. Additionally, Ks analysis and syntenic depth analysis were performed to elucidate its evolutionary history.ResultsThe final assembly yielded a high-quality genome of 679.20 Mb, which was anchored to 8 pseudo-chromosomes with an anchoring rate of 96.5% and a scaffold N50 of 80.50 Mb. The genome assembly showed a high completeness of 97.6% based on Benchmarking with Universal Single-Copy Orthologs (BUSCO) analysis. Repetitive elements constituted approximately 76.8% of the genome, with long terminal repeat retrotransposons (LTRs) accounting for about 39.17%. Ks and syntenic depth analyses revealed that the polyploidization history of three platycodonoid clade species involved only the γ-WGT event. Karyotype evolutionary analysis identified an ancestral karyotype with 9 protochromosomes for the three platycodonoid clade species. Moreover, non-WGD genes, particularly those arising from tandem duplications, were found to contribute significantly to gene family expansion.DiscussionThese findings provide essential insights into the genetic diversity and evolutionary biology of C. pilosula, aiding its conservation and sustainable use.

Infertility is a global health problem affecting millions of people of reproductive age worldwide, with approximately half caused by males. Chitosan oligosaccharide (COS) has strong antioxidant capacity, but its impact on the male reproductive system has not been effectively evaluated. To address this, we integrated RNA-seq, serum metabolomics and intestinal 16 S rDNA analysis to conduct a comprehensive investigation on the male reproductive system. The results showed that COS has potential targets for the treatment of oligospermia, which can promote the expression of meiotic proteins DDX4, DAZL and SYCP1, benefit germ cell proliferation and testicular development, enhance antioxidant capacity, and increase the expression of testicular steroid proteins STAR and CYP11A1. At the same time, COS can activate PI3K-Akt signaling pathway in testis and TM3 cells. Microbiome and metabolomics analysis suggested that COS alters gut microbial community composition and cooperates with serum metabolites to regulate spermatogenesis. Therefore, COS promotes male reproduction by regulating intestinal microorganisms and serum metabolism, activating PI3K-Akt signaling pathway, improving testicular antioxidant capacity and steroid regulation.

By analyzing the change laws of flue gas temperature, steam temperature and working fluid mass flow during a power failure accident in a 660 MW power plant, the change laws of heat load in dense phase zone, transition zone and dilute phase zone over time were obtained. On this basis, a 700 MW ultra-supercritical circulating fluidized bed (CFB) boiler was taken as the research object, the calculation model of flow and heat transfer in water wall after power failure accident was established, and a calculation program for the transient characteristics of the water wall was developed based on the Fortran language. The dense phase zone, transition zone and dilute phase zone were analyzed, respectively. Through calculation, the change laws of the thermal parameters such as water wall metal temperature and working fluid temperature after power failure accident were obtained. The calculation results show that, after the power failure accident, the maximum water wall metal temperature at the outlet of dense phase zone is 558.6 ℃, and the maximum water wall metal temperature at the outlet of dilute phase zone is 579.6 ℃. Therefore, there is no need to equip emergency water supply pump to ensure the safety of the water wall after power failure. The research results can provide guidance for power plants to deal with power failure accidents of ultra-supercritical CFB boilers.

Abstract Background Southwest China is one of the largest karst regions in the world. Karst environment is relatively fragile and vulnerable to human activities. Due to the discharge of sewage and domestic garbage, the karst system may be polluted by pathogenic bacteria. The detection of bacterial distribution and identification of phage capable of infecting them is an important approach for environmental assessment and resource acquisition. Methods Bacteria and phages were isolated from karst water in southwest China using the plate scribing and double plate method, respectively. Isolated phage was defined by transmission electron microscopy, one-step growth curve and optimal multiplicity of infection (MOI). Genomic sequencing, phylogenetic analysis, comparative genomic and proteomic analysis were performed. Results A Klebsiella quasipneumoniae phage was isolated from 32 isolates and named KL01. KL01 is morphologically identified as Caudoviricetes with an optimal MOI of 0.1, an incubation period of 10 min, and a lysis period of 60 min. The genome length of KL01 is about 45 kb, the GC content is 42.5%, and it contains 59 open reading frames. The highest average nucleotide similarity between KL01 and a known Klebsiella phage 6939 was 83.04%. Conclusions KL01 is a novel phage, belonging to the Autophagoviridae, which has strong lytic ability. This study indicates that there were not only some potential potentially pathogenic bacteria in the karst environment, but also phage resources for exploration and application.

The genus Camellia contains three types of domesticates that meet various needs of ancient humans: the ornamental C. japonica, the edible oil-producing C. oleifera, and the beverage-purposed tea plant C. sinensis. The genomic drivers of the functional diversification of Camellia domesticates remain unknown. Here, we present the genomic variations of 625 Camellia accessions based on a new genome assembly of C. sinensis var. assamica (‘YK10’), which consists of 15 pseudo-chromosomes with a total length of 3.35 Gb and a contig N50 of 816,948 bp. These accessions were mainly distributed in East Asia, South Asia, Southeast Asia, and Africa. We profiled the population and subpopulation structure in tea tree Camellia to find new evidence for the parallel domestication of C. sinensis var. assamica (CSA) and C. sinensis var. sinensis (CSS). We also identified candidate genes associated with traits differentiating CSA, CSS, oilseed Camellia, and ornamental Camellia cultivars. Our results provide a unique global view of the genetic diversification of Camellia domesticates and provide valuable resources for ongoing functional and molecular breeding research.

Lamiales, comprising over 23,755 species across 24 families, stands as a highly diverse and prolific plant group, playing a significant role in the cultivation of horticultural, ornamental, and medicinal plant varieties. Whole-genome duplication (WGD) and its subsequent post-polyploid diploidization (PPD) process represent the most drastic type of karyotype evolution, injecting significant potential for promoting the diversity of this lineage. However, polyploidization histories, as well as genome and subgenome fractionation following WGD events in Lamiales species, are still not well investigated. In this study, we constructed a chromosome-level genome assembly of Lindenbergia philippensis (Orobanchaceae) and conducted comparative genomic analyses with 14 other Lamiales species. L. philippensis is positioned closest to the parasitic lineage within Orobanchaceae and has a conserved karyotype. Through a combination of Ks analysis and syntenic depth analysis, we reconstructed and validated polyploidization histories of Lamiales species. Our results indicated that Primulina huaijiensis underwent three rounds of diploidization events following the γ-WGT event, rather than two rounds as reported. Besides, we reconfirmed that most Lamiales species shared a common diploidization event (L-WGD). Subsequently, we constructed the Lamiales Ancestral Karyotype (LAK), comprising 11 proto-chromosomes, and elucidated its evolutionary trajectory, highlighting the highly flexible reshuffling of the Lamiales paleogenome. We identified biased fractionation of subgenomes following the L-WGD event across eight species, and highlighted the positive impacts of non-WGD genes on gene family expansion. This study provides novel genomic resources and insights into polyploidy and karyotype remodeling of Lamiales species, essential for advancing our understanding of species diversification and genome evolution.

Aims: Cellular dormancy is a state of quiescence subpopulation of tumor cells, characterized by low differentiation and lack of mitotic activity. They could evade chemotherapy and targeted therapy, leading to drug resistance and disease recurrence. Recent studies have shown a correlation between dormant cancer cells and unique extracellular matrix (ECM) composition, which is critical in regulating cell behavior. However, their interacting roles in TNBC patients remains to be characterized. Main methods: Dormant cancer cells in MDA-MB-231 cell line with highest PKH26 dye-retaining were FACS-sorted and gene expression was then analyzed. Dormant associated ECM (DA-ECM) signature was characterized by pathway analysis. Unsupervised hierarchical clustering was used to define distinct ECM features for TNBC patients. ECM-specific tumor biology was defined by integration of bulk RNA-seq with single-cell RNA-seq data, analysis of ligand-receptor interactions and enriched biological pathways, and in silico drug screening. We validated the sensitivity of dormant cancer cells to MAPK inhibitors by flow cytometry in vitro. Key findings: We observed that dormant TNBC cells preferentially expressed ∼10 % DA-ECM genes. The DA-ECM High subtype defined by unsupervised hierarchical clustering analysis was associated with immunosuppressive tumor microenvironment. Moreover, ligand-receptor interaction and pathway analysis revealed that the DA-ECM High subtype may likely help maintain tumor cell dormancy through MAPK, Hedgehog and Notch signaling pathways. Finally, in silico drug screening against the DA-ECM signature and in vitro assay showed dormant cancer cells were relatively sensitive to the MAPK pathway inhibitors, which may represent a potential therapeutic strategy for treating TNBC. Significance: Collectively, our research revealed that dormancy-associated ECM characterized tumor cells possess significant ECM remodeling capacity, and treatment strategies towards these cells could improve TNBC patient outcome.

Understanding public emotion on social media about community wellness is crucial for enhancing health awareness and guiding policy-making. In order to more fully mine the deep contextual semantical information of short texts and further enhance the effectiveness of emotion prediction in social media, we propose the Deep Parallel Contextual Analysis Framework (DPCAF) in the community wellness domain, specifically addressing the challenges of limited text length and available semantical features in social media text. Specifically, at the embedding layer, we first utilize two different word embedding techniques to generate high-quality vector representations, aiming to achieve more comprehensive semantical capture, stronger generalization ability, and more robust model performance. Subsequently, in the deep contextual layer, the obtained representations are fused with POS and locational representations, and processed through a deep parallel layer composed of Convolutional Neural Networks and Bidirectional Long Short-Term Memory Network. An attention model is then used to further extract semantical features of social media texts. Finally, these deep parallel contextual representations are post-integrated for emotion prediction. Experiments on a dataset collected from social media regarding community wellness demonstrate that compared to benchmark models, DPCAF achieves at least a 4.81 % increase in Precision, a 3.44 % increase in Recall, and a 10.81 % increase in F1-score. Relative to the most advanced models, DPCAF shows a minimum improvement of 2.65 % in Precision, 3.02 % in Recall, and 2.53 % in F1-score.

Abstract In histopathology, doctors identify diseases by characterizing abnormal cells and their spatial organization within tissues. Polarization microscopy and supervised learning have been proved as an effective tool for extracting polarization parameters to highlight pathological features. Here, we present an alternative approach based on unsupervised learning to group polarization-pixels into clusters, which correspond to distinct pathological structures. For pathological samples from different patients, it is confirmed that such unsupervised learning technique can decompose the histological structures into a stable basis of characteristic microstructural clusters, some of which correspond to distinctive pathological features for clinical diagnosis. Using hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) samples, we demonstrate how the proposed framework can be utilized for segmentation of histological image, visualization of microstructure composition associated with lesion, and identification of polarization-based microstructure markers that correlates with specific pathology variation. This technique is capable of unraveling invisible microstructures in non-polarization images, and turn them into visible polarization features to pathologists and researchers.

In this study, wettability was employed to evaluate the effect of alkali activation by NaOH on different fly ash (FA) particle sizes. The results indicated that the surface wettability of FA particles with 13.8 μm increased from 0.025 g2/s to 0.034 g2/s after activation by the NaOH solution, which is suitable for silane modification and electroless plating. X-ray photoelectron spectroscopy (XPS) was used to analyze whether three kinds of silane coupling agents coated on FA surfaces could detect the chemical bonds between silane coupling agents coated on the FA surface and silver layers by shortening the plating time. The XPS results demonstrated that N-Ag coordination bonds can be detected by reducing silver plating time to 2 min for Ag-plated FA modified by N-(2-aminoethyl)-3-aminopropyltrimethoxysilane (KH792). However, there were no chemical bonds detected for Ag-plated FA modified by γ-(2,3-epoxypropoxy)propytrimethoxysilane (KH560) and methyltrimethoxysilane (MTMS), even when the satellite peak of Ag disappeared after plating for 80 s. The SEM showed that Ag particles agglomerated on FA surfaces, and even a bare surface was found after modification by KH560 and MTMS, which further proved no chemical bonds between silver layers and the silane coupling agents.

Abstract Background The purpose of this study is to explore the related factors of precocious puberty in children. Methods 1239 children who underwent physical examination in our hospital from January 2020 to December 2022 were analyzed, including 198 precocious children and 1041 normal children. According to the age of 198 precocious children and 1041 normal children, 205 normal children were selected, and the remaining 836 normal children were excluded. They were divided into precocious group and normal group. The general data of the two groups were recorded. Logistic regression was used to analyze the influencing factors of precocious puberty in children. Results There were statistically significant differences (P 10 years old), and daily exercise time (

External magnetic field has been employed to improve appearance and suppress defects in the single laser or arc welding, and its physical mechanism in magnetic-field-assisted single laser or arc welding has been clearly clarified. However, few studies on the physical processes in magnetic-field-assisted laser-arc hybrid welding (MFA-LAHW) are conducted and its influencing mechanism is unclear. In this research, a comprehensive three-dimension numerical model is established to investigate the keyhole dynamics and weld pool behaviors in MFA-LAHW under the effect of different magnetic flux density. The results suggest that the interaction between a lower magnetic flux density (≤30 mT) and welding current is induced due to the existence of arc. Compared to the magnetic-field-assisted laser beam welding (MFA-LBW), this interaction induces a stronger Lorentz force up to the order of magnitude of 105 N/m3. The weld pool width is reduced while its length and height are increased because the Lorentz force facilitates the backward flow of thermal fluid, increasing the heat transfer from the keyhole and droplet to the rear weld pool edge. Moreover, the steady magnetic field improves the keyhole stability. The deform on keyhole rear wall brought by the droplet and vortex is suppressed, and keyhole size is widened under steady magnetic field, which reduced keyhole collapse. Furthermore, the comparative analysis with the case in MFA-LBW is carried out and the MFA-LAHW is verified to be more valuable for medium-thickness aluminum alloy. This work provides the underlying physics understanding of MFA-LAHW, which will broaden the application value of LAHW.

The detection of keyhole-induced pore positions is a critical procedure for assessing laser welding quality. Considering the detection error due to pore migration and noise interference, this research proposes a regional prediction model based on the time–frequency-domain features of the laser plume. The original plume signal was separated into several signal segments to construct the morphological sequences. To suppress the mode mixing caused by environmental noise, variational modal decomposition (VMD) was utilized to process the signals. The time–frequency features extracted from the decomposed signals were acquired as the input of a backpropagation (BP) neural network to predict the pore locations. To reduce the prediction error caused by pore migration, the effect of the length of the signal segments on the prediction accuracy was investigated. The results show that the optimal signal segment length was 0.4 mm, with an accuracy of 97.77%. The 0.2 mm signal segments failed to eliminate the negative effects of pore migration. The signal segments over 0.4 mm resulted in prediction errors of small and dense pores. This work provides more guidance for optimizing the feature extraction of welding signals to improve the accuracy of welding defect identification.

A staggered vane-shaped slot-line slow-wave structure (SV-SL SWS) for application in W-band traveling wave tubes (TWTs) is proposed in this article. In contrast to the conventional slot-line SWSs with dielectric substrates, the proposed SWS consists only of a thin metal sheet inscribed with periodic grooves and two half-metal enclosures, which means it can be easily manufactured and assembled and has the potential for mass production. This SWS not only solves the problem of the dielectric loading effect but also improves the heat dissipation capability of such structures. Meanwhile, the SWS design presented here covers a −15 dB S11 frequency range from 87.5 to 95 GHz. The 3-D simulation for a TWT based on the suggested SWS is also investigated. Under dual-electron injection conditions with a total voltage of 17.2 kV and a total current of 0.3 A, the maximum output power at 90 GHz is 200 W, with a 3 dB bandwidth up to 4 GHz. With a good potential for fabrication using microfabrication techniques, this structure can be a good candidate for millimeter-wave TWT applications.

High speed cutting is an effective technique to achieve high efficiency and high quality machining of titanium alloy and other difficult materials. The high speed cutting process of titanium alloy has the nonlinear dynamic characteristics of high temperature, high strain and high strain rate. In order to accurately describe the dynamic mechanical behavior of titanium alloy in high speed cutting, the research on dynamic constitutive model of titanium alloy is reviewed. The application conditions, advantages and disadvantages of Johnson-Cook model, Zerilli-Armstrong model and Bammann model are analyzed from the perspective of phenomenological model and physical model with Ti-6Al-4V as the research object. After comprehensive comparison, the Johnson-Cook model is selected for further exploration, and the Johnson-Cook modified model is classified based on the influence of temperature and competition mechanism. The prediction accuracy of the Johnson-Cook modified model is improved compared with that of the classical model. At the same time, it is proposed that the construction of phenomenology-physics composite constitutive model can be taken as the key direction to explore the dynamic constitutive model of titanium alloy, and the method of experiment and computer synchronization can be used to obtain the optimal solution of constitutive model parameters, so as to improve the prediction accuracy of dynamic constitutive model.

Abstract Point cloud registration is of great significance to the reconstruction of high‐precision 3D city models. There are some challenges when aligning aerial and close‐range photogrammetric point clouds, such as huge view differences caused by the different sights of the sensors, massive noisy points due to the error in dense matching, and scale uncertainty since there are no control points for absolute orientation. To achieve complementary advantages of aerial and close‐range point clouds, in this paper, a robust cross‐source point clouds registration method is proposed using image visual context features and scale consistency. First, a cross‐view image matching method based on image visual context features is proposed to obtain corresponding points. Second, to overcome the challenges of noisy points and scale differences, an outlier filtering method is designed based on scale consistency. Finally, the dual quaternions model considering the scale factor is introduced to solve the spatial transformation model. To analyze the feasibility of this method qualitatively and quantitatively, experiments are conducted using the public scene dataset of Dortmund, Germany, and the scene dataset of Zhengzhou City, China. Three kinds of cross‐source point clouds registration experiments are conducted in this paper, including aerial and close‐range point clouds registration in Dortmund, and aerial and ground point clouds registrations in both Dortmund and Zhengzhou. The chamfer distances of the three sets of experiments are 4.48 m, 5.97 m and 4.78 m, respectively. The ablation study shows that the outlier filtering method and the dual quaternions model improve the accuracy by at least 14% and 25%, respectively. The experiments demonstrate that the method accomplishes the cross‐source point clouds registration in large‐scale scenes accurately and efficiently, providing a solid foundation for subsequent fine 3D reconstruction.

Abstract Background Osteosarcoma (OSA) presents a clinical challenge and has a low 5‐year survival rate. Currently, the lack of advanced stratification models makes personalized therapy difficult. This study aims to identify novel biomarkers to stratify high‐risk OSA patients and guide treatment. Methods We combined 10 machine‐learning algorithms into 101 combinations, from which the optimal model was established for predicting overall survival based on transcriptomic profiles for 254 samples. Alterations in transcriptomic, genomic and epigenomic landscapes were assessed to elucidate mechanisms driving poor prognosis. Single‐cell RNA sequencing (scRNA‐seq) unveiled genes overexpressed in OSA cells as potential therapeutic targets, one of which was validated via tissue staining, knockdown and pharmacological inhibition. We characterized changes in multiple phenotypes, including proliferation, colony formation, migration, invasion, apoptosis, chemosensitivity and in vivo tumourigenicity. RNA‐seq and Western blotting elucidated the impact of squalene epoxidase (SQLE) suppression on signalling pathways. Results The artificial intelligence‐derived prognostic index (AIDPI), generated by our model, was an independent prognostic biomarker, outperforming clinicopathological factors and previously published signatures. Incorporating the AIDPI with clinical factors into a nomogram improved predictive accuracy. For user convenience, both the model and nomogram are accessible online. Patients in the high‐AIDPI group exhibited chemoresistance, coupled with overexpression of MYC and SQLE, increased mTORC1 signalling, disrupted PI3K–Akt signalling, and diminished immune infiltration. ScRNA‐seq revealed high expression of MYC and SQLE in OSA cells. Elevated SQLE expression correlated with chemoresistance and worse outcomes in OSA patients. Therapeutically, silencing SQLE suppressed OSA malignancy and enhanced chemosensitivity, mediated by cholesterol depletion and suppression of the FAK/PI3K/Akt/mTOR pathway. Furthermore, the SQLE‐specific inhibitor FR194738 demonstrated anti‐OSA effects in vivo and exhibited synergistic effects with chemotherapeutic agents. Conclusions AIDPI is a robust biomarker for identifying the high‐risk subset of OSA patients. The SQLE protein emerges as a metabolic vulnerability in these patients, providing a target with translational potential.

Background: Osteosarcoma, the most common primary malignant bone tumor, is currently treated with surgery combined with chemotherapy, but the limited availability of targeted drugs contributes to a poor prognosis. Identifying effective therapeutic targets is crucial for improving the prognosis of osteosarcoma patients. Methods: We screened the DepMap database to identify essential genes as potential therapeutic targets for osteosarcoma. Gene Set Enrichment Analysis (GSEA) was employed to elucidate the biological roles of these essential genes. Promising candidates were filtered through univariate and multivariate Cox analyses, as well as Kaplan-Meier survival analyses using the GSE21257-OSA and TARGET-OSA datasets. The functional role of the target gene was assessed through cell experiments. Additionally, an in situ nude mice model was established to observe the gene's function, and RNA sequencing was utilized to explore the underlying molecular mechanism. Results: A total of 934 essential genes were identified based on their effects (Chronos) using the DepMap database. These genes were primarily enriched in the ribosome pathway according to GSEA analysis. Among them, 195 genes were associated with the ribosome pathway. Rps28, Rps7, and Rps25 were validated as promising candidates following univariate and multivariate Cox analyses of the TARGET-OSA and GSE21257-OSA datasets. Kaplan-Meier survival analyses indicated Rps28 represented an especially promising target, with high expression correlating with poor prognosis. Knockdown of small ribosomal subunit protein eS28, the protein of Rps28, inhibited proliferation, migration, and invasion in both in vitro and in vivo experiments. Silencing RPS28 affected the MAPK signaling pathway in osteosarcoma. Conclusion: In summary, Rps28 has been identified as an essential gene for osteosarcoma cell survival and eS28 may serve as a potential vulnerability in osteosarcoma.

Amidst the framework of dual circulation, innovation emerges as a pivotal strategy for realizing high-quality economic development. Concurrently, digital finance, serving as a potent complement to traditional financial systems, significantly influences regional innovation enhancement. This research employs a spatial panel methodology to thoroughly investigate the inherent mechanisms through which digital finance development shapes regional innovation. Empirical testing is conducted using panel data derived from 283 mainland Chinese prefecture-level cities spanning from 2013 to 2020. The findings underscore that digital inclusive finance plays a crucial role in amplifying regional innovation output, unveiling a distinct spatial impact on innovation. The progression of each facet of digital finance contributes to mitigating supply-side financing constraints, thereby directly fostering heightened regional innovation. The study delves into a Chinese regional sub-sample, revealing a prevalent driving effect with conspicuous heterogeneity across the major regions—East > Central > West. As scientific and technological innovation stands as the primary driving force, its profound interplay with the evolution of financial inclusion in China is evident. This study provides valuable insights to fortify regional modernization efforts and serves as a reference for policymakers and researchers navigating the complex intersection of finance and innovation in the Chinese context.

AbstractRapid urbanization currently poses a threat to cropland areas. Therefore, exploring the pattern of change in cropland areas and its driving mechanism is of great significance in safeguarding regional economic development and food security. In this study, data regarding cropland in the Changsha-Zhuzhou-Xiangtan city group (CZTCG) from 2000 to 2020 were collected, and dynamic changes in cropland in the past 20 years were analyzed. Based on this, the mechanisms that drive cropland change were explored in the context of multiple dimensions. Furthermore, an Inertial Development Scenario and a Cropland Priority Scenario were designed to simulate land use/land cover (LULC) changes in the CZTCG in 2025 and 2035, and, in particular, to analyze the characteristics of future spatiotemporal changes of cropland. The results demonstrated that the cropland area in the CZTCG in the past 20 years has shown a two-stage trend of increasing (2000–2015, increase of 8.25%) and decreasing (2015–2020, decrease of 2.91%), and the main reasons for cropland loss in the whole process of change were forest and building, with serious loss of cropland area in Changsha County and Wangcheng District. Between 2000 and 2020, socio-economic factors (GDP, total agricultural output), topography (elevation, slope), and climate change (average annual temperature, annual precipitation) were highly correlated with changes in cropland area, exhibiting significant temporal and regional variability. The simulation results indicate that until 2035, the Cropland Priority Scenario shows a significant increase in the area of cropland in the study area compared to the Inertial Development Scenario. Consequently, the implementation of a strategy that prioritizes cropland can effectively protect it, while helping to promote ecological development and regional socio-economic development.

Blockchain technology has become more common in the audit industry, posing new problems for traditional audit work. Researchers have been studying the effect of customers’ use of blockchain technology on audits, especially on audit risk and audit methods. This paper examines audit cases of Chinese enterprises that use blockchain technology. It analyzes the effect of the use of blockchain technology on the audit and the new audit problems. It also examines an Australian blockchain audit case using a questionnaire. This case study showed that the application of new technologies to the audit industry may lead to increased inherent risks and control risks. The audit methodology is uncertain and there are two possible approaches: (1) a combination of direct, indirect, account-level, and entity-level evidence and (2) an increase in indirect and entity-level evidence. This paper puts forward the reference case of the Australian blockchain audit experience and suggestions for developing blockchain audits in China.

Background: Presbycusis/Age-related hearing loss is a sensorineural hearing loss caused by age-related deterioration of the auditory system that poses a risk to the physical and mental health of older people, including social and cognitive decline. It is also associated with frailty, falls and depression. There are currently no specific medications for the treatment of presbycusis, and early detection and intervention are key to its prevention and management. Traditional Chinese medicine interventions may offer opportunities in the prevention and treatment of presbycusis, but there is no relevant review. Methods: Literature searches was conducted using PubMed, Cochrane Library, Web of Science, and China National Knowledge Infrastructure (CNKI) databases for review articles, research articles, clinical trials, meta-analyses, and case studies in animal models and clinical trials. Results: We summarized the pathological mechanisms associated with presbycusis, related to genetic factors, environment, lifestyle, and molecular mechanisms related to oxidative stress, mitochondrial dysfunction, and inflammatory pathways. It is suggested that traditional Chinese medicine interventions may offer opportunities in the prevention and treatment of presbycusis using active ingredients of herbs or formulas, acupuncture, and exercise such as Tai Chi Chuan or Ba Duan Jin. The active ingredients of herbs or formulas may exert ear protection through Nrf2-mediated antioxidant pathways, NF-kB and NLRP3-related anti-inflammatory signaling, and regulation of autophagy. Conclusions: Here, we review the pathogenetic factors and pathological mechanisms involved in presbycusis, as well as traditional Chinese medicine interventions and treatments, with the aim of providing a new perspective for the prevention and treatment of hearing loss in the elderly and further improving their quality of life.

Summary: In vitro embryonic analogue models, such as gastruloids, trunk-like structures and embryoids, have been developed to understand principles of early development and morphogenesis. However, models that can fully mimic head formation are still missing. Here, we present a protocol for generating the head-like structure (HLS) in zebrafish embryonic explants. We describe steps for dissection and constructing cell and patterning landscapes. We then detail assessment of this structure through axis induction.For complete details on the use and execution of this protocol, please refer to Cheng et al. (2023).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

AbstractMacropodus hongkongensis (Freyhof & Herder, 2002), is sparsely distributed in Hong Kong and Guangdong provinces. Recently, a new geographical population of M. hongkongensis was discovered in the Wanquan River in the Hainan province. Therefore, this study focused on sequencing the complete mitochondrial genome of the new geographical population of Macropodus hongkongensis from the Wanquan River. The circular mtDNA molecule was 16,492 bp in size, and the overall base compositions were A (30.30%), C (24.90%), T (29.80%), and G (15.00%), with a slight bias toward A + T. The complete mitogenome encoded 13 protein-coding genes (PCGs), 22 tRNA genes, 2 rRNA genes, and a control region. Phylogenetic analysis indicated that M. hongkongensis of the Hainan Wanquan River was most closely related to the M. hongkongensis of the Gongdong population. These results provide useful genetic information for species identification and phylogenetic studies of Macropodus species.

Abstract Background Urinary bladder cancer (UBC) is a common malignancy of the urinary tract; however, the mechanism underlying its high recurrence and responses to immunotherapy remains unclear, making clinical outcome predictions difficult. Epigenetic alterations, especially DNA methylation, play important roles in bladder cancer development and are increasingly being investigated as biomarkers for diagnostic or prognostic predictions. However, little is known about hydroxymethylation since previous studies based on bisulfite-sequencing approaches could not differentiate between 5mC and 5hmC signals, resulting in entangled methylation results. Methods Tissue samples of bladder cancer patients who underwent laparoscopic radical cystectomy (LRC), partial cystectomy (PC), or transurethral resection of bladder tumor (TURBT) were collected. We utilized a multi-omics approach to analyze both primary and recurrent bladder cancer samples. By integrating various techniques including RNA sequencing, oxidative reduced-representation bisulfite sequencing (oxRRBS), reduced-representation bisulfite sequencing (RRBS), and whole exome sequencing, a comprehensive analysis of the genome, transcriptome, methylome, and hydroxymethylome landscape of these cancers was possible. Results By whole exome sequencing, we identified driver mutations involved in the development of UBC, including those in FGFR3, KDMTA, and KDMT2C. However, few of these driver mutations were associated with the down-regulation of programmed death-ligand 1 (PD-L1) or recurrence in UBC. By integrating RRBS and oxRRBS data, we identified fatty acid oxidation-related genes significantly enriched in 5hmC-associated transcription alterations in recurrent bladder cancers. We also observed a series of 5mC hypo differentially methylated regions (DMRs) in the gene body of NFATC1, which is highly involved in T-cell immune responses in bladder cancer samples with high expression of PD-L1. Since 5mC and 5hmC alternations are globally anti-correlated, RRBS-seq-based markers that combine the 5mC and 5hmC signals, attenuate cancer-related signals, and therefore, are not optimal as clinical biomarkers. Conclusions By multi-omics profiling of UBC samples, we showed that epigenetic alternations are more involved compared to genetic mutations in the PD-L1 regulation and recurrence of UBC. As proof of principle, we demonstrated that the combined measurement of 5mC and 5hmC levels by the bisulfite-based method compromises the prediction accuracy of epigenetic biomarkers.

Quantum sensors based on NV centers in diamond are well established, however the sensitivity of detection of high-frequency radio signals has been limited. Here the authors use nanoscale field-focusing to enhance sensitivity and demonstrate ranging for GHz radio signals in an interferometer set-up.

Abstract Despite the success of targeted therapies in cancer treatment, therapy-induced resistance remains a major obstacle to a complete cure. Tumor cells evade treatments and relapse via phenotypic switching driven by intrinsic or induced cell plasticity. Several reversible mechanisms have been proposed to circumvent tumor cell plasticity, including epigenetic modifications, regulation of transcription factors, activation or suppression of key signaling pathways, as well as modification of the tumor environment. Epithelial-to-mesenchymal transition, tumor cell and cancer stem cell formation also serve as roads towards tumor cell plasticity. Corresponding treatment strategies have recently been developed that either target plasticity-related mechanisms or employ combination treatments. In this review, we delineate the formation of tumor cell plasticity and its manipulation of tumor evasion from targeted therapy. We discuss the non-genetic mechanisms of targeted drug-induced tumor cell plasticity in various types of tumors and provide insights into the contribution of tumor cell plasticity to acquired drug resistance. New therapeutic strategies such as inhibition or reversal of tumor cell plasticity are also presented. We also discuss the multitude of clinical trials that are ongoing worldwide with the intention of improving clinical outcomes. These advances provide a direction for developing novel therapeutic strategies and combination therapy regimens that target tumor cell plasticity.

Summary: The role of alternative polyadenylation (APA) in tumor development is becoming increasingly evident, but the impact of APA events on the prognosis of LUAD patients is unclear. Therefore, in the present study, we aimed to analyze specific APA events in LUAD to identify novel prognostic biomarkers for LUAD. We first identified prognostic candidate genes for LUAD associated with APA events and validated them in both the East Asian and the USA cohorts, finding that five genes (DCUN1D5, PSMC4, TFAM, THRA, and TMEM100) were of prognostic significance in both populations. Based on this, an APA-based prognostic signature was constructed for the East Asian population. The predictive accuracy of the prognostic signature was further evaluated by the time-dependent ROC, with 1-, 2-, and 3-year AUCs of 0.86, 0.81, and 0.71, respectively. This study may provide new markers for individualized diagnosis and prognostic assessment of LUAD and potential targets for precision treatment.

Mueller matrix imaging is emerging for the quantitative characterization of pathological microstructures and is especially sensitive to fibrous structures. Liver fibrosis is a characteristic of many types of chronic liver diseases. The clinical diagnosis of liver fibrosis requires time-consuming multiple staining processes that specifically target on fibrous structures. The staining proficiency of technicians and the subjective visualization of pathologists may bring inconsistency to clinical diagnosis. Mueller matrix imaging can reduce the multiple staining processes and provide quantitative diagnostic indicators to characterize liver fibrosis tissues. In this study, a fiber-sensitive polarization feature parameter (PFP) was derived through the forward sequential feature selection (SFS) and linear discriminant analysis (LDA) to target on the identification of fibrous structures. Then, the Pearson correlation coefficients and the statistical T-tests between the fiber-sensitive PFP image textures and the liver fibrosis tissues were calculated. The results show the gray level run length matrix (GLRLM)-based run entropy that measures the heterogeneity of the PFP image was most correlated to the changes of liver fibrosis tissues at four stages with a Pearson correlation of 0.6919. The results also indicate the highest Pearson correlation of 0.9996 was achieved through the linear regression predictions of the combination of the PFP image textures. This study demonstrates the potential of deriving a fiber-sensitive PFP to reduce the multiple staining process and provide textures-based quantitative diagnostic indicators for the staging of liver fibrosis.

ObjectiveThis study aimed to explore the hemodynamic changes before and after anastomosis in patients with Moyamoya disease (MMD) using multiple models.MethodsWe prospectively enrolled 42 MMD patients who underwent combined revascularization. Intraoperative FLOW800 was performed before and after anastomosis, and parameters was collected, including maximum intensity, delay time, rise time, slope, blood flow index, and microvascular transit time (MVTT). Additionally, preoperative and postoperative hemodynamic parameters were measured using color Doppler ultrasonography (CDUS), including peak systolic velocity, end-diastolic velocity, resistance index (RI), pulsatility index (PI), and flow volume. Subsequently, the correlation between FLOW800 and CDUS parameters was explored.ResultsA total of 42 participants took part with an average age of 46.5 years, consisting of 19 men and 23 women. The analysis of FLOW800 indicated that both the delay time and rise time experienced a substantial decrease in both the recipient artery and vein. Additionally, the MVTT was found to be significantly reduced after the surgery (5.7 ± 2.2 s vs. 4.9 ± 1.6, p = 0.021). However, no statistically significant differences were observed among the other parameters. Similarly, all postoperative parameters in CDUS hemodynamics exhibited significant alterations in comparison to the preoperative values. The correlation analysis between FLOW800 and CDUS parameters indicated a significant association between MVTT and RI and PI, no significant relationships were found among the other parameters in the two groups.ConclusionThe hemodynamic outcomes of the donor and recipient arteries demonstrated significant changes following bypass surgery. The parameter of time appears to be more precise and sensitive in assessing hemodynamics using FLOW800. Multiple evaluations of hemodynamics could offer substantial evidence for perioperative management.

Abstract Moyamoya disease (MMD) is a chronic occlusive cerebrovascular disease that can be treated with revascularization. Surgery increases the risk of poor wound healing (PWH) due to the impact on the blood supply to the flap. We aimed to analyze risk factors for PWH in MMD with a complete Y-shaped incision. A total of 125 patients with MMD were enrolled in this prospective observational study. The wounds were assessed and measured on the third and seventh days after surgery. The mean age of these patients was 43.3 ± 10.0 years. The ratio of male to female was 1:1.3. 15 (12.0%) patients had incision complications. 5 patients (4.0%) had redness; 2 patients (1.6%) had swelling; 2 patients (1.6%) had fat necrosis; 3 patients (2.4%) had incision infection; and 3 patients (2.4%) had flap necrosis. Student’s t test showed significant differences in BMI (P = 0.040) and fever time (P = 0.050). The standard chi-squared test showed significant differences in incision infection (P = 0.010), suture mode (P = 0.047), and cutting off large branch vessels in the flap (P

Abstract Objective Standard medical treatment for early non‐small cell lung cancer (NSCLC) is surgery; however, stereotactic body radiotherapy (SBRT) can be a viable substitute for elderly patients who can no longer tolerate or refuse surgery. The unsurpassed care for elderly patients with early NSCLC remains inconclusive. We conducted a propensity‐score matching analysis to compare the efficacy and side‐effects of SBRT and video‐assisted thoracic surgery (VATS) in elderly patients with pathologically‐proven early NSCLC. Methods This single‐institution retrospective study included 310 elderly patients who underwent VATS (n = 180) or SBRT (n = 130) from January 2011 to November 2018 at the Tianjin Medical University Cancer Institute and Hospital. Sex, performance status, pathology type, Charlson Comorbidity Index, and T‐stage according to the eighth tumor node metastasis classification were considered when performing propensity‐score matching. Results After propensity‐score matching, 71 patients were included in each group for analysis. A median follow‐up period of 53.5 months was observed for all patients; 72 and 53 months for patients undergoing VATS and SBRT, respectively. Overall survival (p = 0.492), progression‐free survival (p = 0.294), locoregional recurrence‐free survival (p = 0.866), and distant metastasis‐free survival (p = 0.452) did not differ significantly between the VATS and SBRT groups. Multivariate analysis showed a significant correlation between the T‐stage and overall survival. However, treatment‐related toxicity was lower in the SBRT group than in the VATS group. Conclusions SBRT is an option comparable with surgery for elderly patients with pathologically‐proven early‐stage NSCLC.