Search

Abstract Acute myeloid leukemia (AML) with mixed-lineage leukemia (MLL) gene rearrangements (MLL-r) is an aggressive subtype of blood cancer with dismal prognosis, underscoring the urgent need for novel therapeutic strategies. E1A-binding protein (EP300) and CREB-binding protein (CREBBP) function as essential transcriptional coactivators and acetyltransferases, governing leukemogenesis through diverse mechanisms. Targeting EP300/CREBBP holds great promise for treating leukemia with some certain cytogenetic abnormalities. Here, we demonstrated that EP300 and CREBBP are core epigenetic regulators in the pathogenesis of MLL-r AML through assaying the transposase-accessible chromatin with high-throughput sequencing (ATAC-seq). Knocking-out EP300/CREBBP and inhibitor (A-485) treatment depressed the MLL-r cells proliferation, while the MLL wild-type cells remained uninfluenced. We found that the CDK4/RB/E2F axis was downregulated specifically in MLL-r AML cell after A-485 treatment by RNA-seq, western blot and cut-tag analyses. EP300/CREBBP inhibitor selectively exerted potent anti-leukemia activity through blocking the MLL-r-BET complex binding to H3K27Ac modification on critical genes loci, distinct from global histone acetylation. Collectively, our study identified EP300/CREBBP as a critical epigenetic driver of MLL-r leukemia and validated their therapeutic potential through targeting inhibition, offering a promising avenue for improving clinical outcomes in this aggressive leukemia.

Abstract Emerging evidence indicates that transfer RNA (tRNA)‐derived small RNAs (tsRNAs), originated from tRNA with high abundance RNA modifications, play an important role in many complex physiological and pathological processes. However, the biological functions and regulatory mechanisms of modified tsRNAs in cancer remain poorly understood. Here, it is screened for and confirmed the presence of a novel m7G‐modified tsRNA, m7G‐3′‐tiRNA LysTTT (mtiRL), in a variety of chemical carcinogenesis models by combining small RNA sequencing with an m7G small RNA‐modified chip. Moreover, it is found that mtiRL, catalyzed by the tRNA m7G‐modifying enzyme mettl1, promotes bladder cancer (BC) malignancy in vitro and in vivo. Mechanistically, mtiRL is found to specifically bind the oncoprotein Annexin A2 (ANXA2) to promote its Tyr24 phosphorylation by enhancing the interactions between ANXA2 and Yes proto‐oncogene 1 (Yes1), leading to ANXA2 activation and increased p‐ANXA2‐Y24 nuclear localization in BC cells. Together, these findings define a critical role for mtiRL and suggest that targeting this novel m7G‐modified tsRNA can be an efficient way for to treat BC.

Ascribing to the abundance of Ti element, exceptional electrical conductivity, and electrocatalytic performance, titanium carbide MXene (Ti3C2Tx, MX) is considered as an ideal conductive matrix and employed for in situ preparation of promising TiO2 NPs@MX/reduced graphene oxide (rGO) heterojunction electrodes for uric acid (UA) detection. However, the incapability of achieving the controllable growth and synthesis of TiO2 nanoparticles (NPs) on MX nanosheets is a bottleneck in fabricating optimal and controllable TiO2 NPs@MX hybrid. Herein, an “on‐site transformation strategy” is developed to synthetize TiO2 NPs@MX/rGO heterojunction platform controllably by in situ electrochemical oxidizing MX nanosheets at various treatment times. The proposed approach allows for the greater operability to controllably grow and synthetize TiO2 NPs on the surface of MX nanosheets. The heterojunction electrodes present a linear voltammetric response toward UA in the concentration range of 0.003–0.3 and 0.3–300 μm and a low detection limit of 0.78 nm (S/N = 3). Additionally, a handheld electrochemical system with a smartphone readout is developed for point‐of‐care health monitoring, enabling fast, precise, and specific recognition of UA in real urine samples. The study provides a facile and controllable approach to fabricate TiO2 NPs@MX/rGO heterojunction platform for future use in other biomolecules' detection.

Traditional methods for water quality assessment often overlook the uncertainty of water quality data during the sample collection process, leading to limitations in their application. Therefore, this study combines the comprehensive water quality index (CWQI) method and the improved CWQI method based on CRITIC with the Monte Carlo method to evaluate the water quality in the Weishui Reservoir watershed. The results indicate that (1) there is a noticeable difference in water quality between the Shaxiping and Dayanzui sampling points. The water quality at the Shaxiping sampling point is excellent, with a water quality classification of Class I. In contrast, the water quality at the Dayanzui sampling point is comparatively poorer, with an average water quality classification of Class III. (2) Sensitivity analysis shows that TN, NH4+-N, and TP are more sensitive than other indicators, suggesting that they are the primary factors influencing the evaluation results. (3) Compared to the traditional CWQI method, combining the CRITIC-based improved CWQI method with the Monte Carlo method is more scientifically rigorous. It considers the variety of evaluation indicators, allocates weights rationally, and provides evaluation results that align better with seasonal variations, resulting in higher discriminative power. HIGHLIGHTS A new model integrating Monte Carlo simulation, CRITC methods, and CWQI was proposed to assess water quality in Weishui Reservoir.; Compared with the conventional model (CWQI), the new model leads to more reasonable results.; The key parameters affecting water quality in Weishui Reservoir are TN, TP, and NH4+-N.;

Abstract Background and objective This study comprehensively evaluates the distribution patterns and antimicrobial resistance profiles of urinary pathogens in Preoperative midstream urine cultures collected from patients with urinary calculi in China over the last two decades. Methods A cross-sectional analysis of 41 studies was conducted. A systematic search across various databases, including Wanfang Data, CNKI, SinoMed, Embase, PubMed, and Web of Science, was carried out, covering the time period from 2002 to 2022. Using R 4.2.1 software, a meta-analysis was performed to assess heterogeneity using Cochran’s Q test and the I2 statistic. Results In the analysis of preoperative midstream urine cultures from Chinese patients with urinary calculi, gram-negative bacteria dominated at 69%, with Escherichia coli (43%), Klebsiella pneumoniae (8%), Proteus mirabilis (6%), Pseudomonas aeruginosa (5%), Acinetobacter baumannii (3%), and Enterobacter cloacae (4%) being prominent. Gram-positive organisms included Enterococcus faecalis (9%), Enterococcus faecium (5%), and Staphylococcus aureus (4%). Over time, proportions of Proteus mirabilis, Enterococcus faecalis, and Staphylococcus aureus decreased, while Klebsiella pneumoniae and Pseudomonas aeruginosa increased. Notably, Escherichia coli proportion reduced from 37 to 33% within the last two decades. Antimicrobial resistance analysis indicated declining resistance in E. coli (e.g., co-trimoxazole from 73 to 55%, gentamicin from 64 to 40%), but rising resistance in piperacillin and cefotaxime (34–60%). Enterococcus faecalis exhibited increasing resistance to ampicillin (5–69%), gentamicin (59–94%), and tetracycline (77–89%) over time, while resistance to levofloxacin and ciprofloxacin notably decreased (72–16% and 49–8%, respectively). Conclusion Over the past two decades, the proportion of gram-negative bacteria was declined, while the proportion of gram-positive bacteria increased. Escherichia coli remained the most common pathogen in the urine culture of patients with urinary calculi in China and the resistance of Escherichia coli to commonly used antibiotics increased. Clinicians should select appropriate antibiotics according to the results of urine culture and drug sensitivity test to reduce the occurrence of antibiotic resistance.

Several fungal pathogens cause root rot of common bean, among which Fusarium spp. are the most common pathogens causing Fusarium root rot (FRR) worldwide. FRR has been becoming an increasingly severe disease of common bean in China, but the species of Fusarium spp. have remained unclear. Thus, this study was performed to identify the pathogen causing common bean root rot in Liangcheng County, Inner Mongolia, China. Nineteen Fusarium-like isolates were obtained after pathogen isolation and purification. The pathogenicity test indicated that eight isolates caused severe disease symptoms on common bean, while 11 other isolates were not pathogenic. The eight pathogenic isolates, FCL1–FCL8, were identified as Fusarium cuneirostrum by morphological characterization and phylogenetic analysis using partial sequences of EF-1α, ITS, 28S, and IGS regions. Host range test showed that the representative F. cuneirostrum isolate FCL3 was also pathogenic to mung bean, while not pathogenic to adzuki bean, chickpea, cowpea, faba bean, pea, and soybean. Moreover, 50 common bean and 50 mung bean cultivars were screened for resistance to FRR, and seven highly resistant or resistant cultivars of common bean were identified, while no resistant cultivars of mung bean were screened. This study revealed that F. cuneirostrum was one of common bean FRR pathogens in Inner Mongolia and it could induce mung bean root rot as well. To our knowledge, this is the first report of F. cuneirostrum causing FRR of common bean in China.

The vehicle load on a bridge is a critical and dynamic variable. It adversely affects bridges, especially when overloading occurs. Bridges are prone to fatigue damage or collapse. Therefore, identifying the size and type of dynamic vehicle loads on bridges is critical for theoretical studies and practical applications, such as health monitoring, daily maintenance, safety assessment, and traffic planning. The paper proposes a method for identifying the dynamic load parameters based on a convolutional neural network (CNN) and dynamic strain data. The model is implemented in MATLAB. An initial finite-element model of a three-span precast beam bridge is established in the software ABAQUS and modified by combining the modal and experimental data derived from a segmental girder bridge. The dynamic strain response of the bridge under a moving vehicle load is simulated under different working conditions. The results are used as the training data of the CNN to identify the vehicle’s position, speed, and load on the bridge. The high prediction accuracy indicates the proposed model’s suitability for identifying the dynamic load parameters.

Abstract Background The value of SyMRI‐derived parameters from lumbar marrow for predicting early treatment response and optimizing the risk stratification of the Revised International Staging System (R‐ISS) in participants with multiple myeloma (MM) is unknown. Methods We prospectively enrolled participants with newly diagnosed MM before treatment. The SyMRI of lumbar marrow was used to calculate T1, T2, and PD values and the clinical features were collected. All participants were divided into good response (≥VGPR) and poor response (

BackgroundGlioma is the most common cancer of the central nervous system with poor therapeutic response and clinical prognosis. Insulin-like growth factor 1 receptor (IGF-1R) signaling is implicated in tumor development and progression and induces apoptosis of cancer cells following functional inhibition. However, the relationship between the IGF-1R-related signaling pathway genes and glioma prognosis or immunotherapy/chemotherapy is poorly understood.MethodsLASSO–Cox regression was employed to develop a 16-gene risk signature in the TCGA-GBMLGG cohort, and all patients with glioma were divided into low-risk and high-risk subgroups. The relationships between the risk signature and the tumor immune microenvironment (TIME), immunotherapy response, and chemotherapy response were then analyzed. Immunohistochemistry was used to evaluate the HSP90B1 level in clinical glioma tissue.ResultsThe gene risk signature yielded superior predictive efficacy in prognosis (5-year area under the curve: 0.875) and can therefore serve as an independent prognostic indicator in patients with glioma. The high-risk subgroup exhibited abundant immune infltration and elevated immune checkpoint gene expression within the TIME. Subsequent analysis revealed that patients in the high-risk subgroup benefited more from chemotherapy. Immunohistochemical analysis confirmed that HSP90B1 was overexpressed in glioma, with significantly higher levels observed in glioblastoma than in astrocytoma or oligodendrocytoma.ConclusionThe newly identified 16-gene risk signature demonstrates a robust predictive capacity for glioma prognosis and plays a pivotal role in the TIME, thereby offering valuable insights for the exploration of novel biomarkers and targeted therapeutics.

Abstract High-performance micro-electro-mechanical system (MEMS) gyrocompasses for north-finding systems have been very popular for decades. In this paper, a MEMS north-finding system (NFS) based on virtual maytagging (VM) is presented for the first time. In stark contrast to previous schemes of MEMS-based NFSs (e.g., carouseling, maytagging) and the abandoning rate table, we developed a honeycomb disk resonator gyroscope (HDRG) and two commercial accelerometers for azimuth detection. Instead of the physical rotation of the integrated turntable in traditional NFSs, the vibratory working modes of the HDRG are rotated periodically with electronic control to reduce the uncertainty in the azimuth. After systematically analyzing the principle of NFSs with VM, we designed tests to verify the practicability at the sensor level. A bias instability of 0.0078°/h can be obtained during one day with VM in an HDRG. We also implemented comparative north-finding experiments to further check our strategy at the system level. The accuracy in the azimuth can reach 0.204° for 5 min at 28.2° latitude with VM and 0.172° with maytagging. The results show that without any mechanical turning parts, VM technology makes it possible to develop high-precision handheld MEMS NFSs.

Chickpea (Cicer arietinum L.) is an important legume crop worldwide. An emerging disease, basal stem rot with obvious wilt symptoms, was observed in the upper part of chickpea plants during the disease survey in Qiubei County of Yunnan Province. Three fungal isolates (ZD36-1, ZD36-2, and ZD36-3) were obtained from the diseased tissue of chickpea plants collected from the field. Those isolates were morphologically found to be similar to Diaporthe aspalathi. Molecular sequence analyses of multiple gene regions (ITS, tef1, tub2, cal, and his3) indicated that the three isolates showed a high identity with D. aspalathi. Pathogenicity and host range tests of the isolates were performed on the original host chickpea and eight other legume crops. The isolates were strongly pathogenic to chickpea and appeared highly pathogenic to soybean, cowpea, and mung bean; moderated or mild pathogenic to adzuki bean and common bean; however, the isolates did not cause symptoms on grass pea (Lathyrus sativus). Diaporthe aspalathi was previously reported as a main pathogen causing the southern stem canker in soybean. To our knowledge, this is the first report of D. aspalathi inducing basal stem rot on chickpea worldwide.

In order to study the stiffness degradation of pre-stressed concrete T-beams throughout their entire service life, full-scale destructive tests were conducted on newly constructed T-beams. The test process characterized the relationship between load and deflection at different load levels. Meanwhile, the equivalent stiffness and short-term stiffness of the T-beams at different load levels were calculated based on formulas from the code, and a segmental stiffness back-calculation method for pre-stressed concrete T-beam bridges was proposed based on system identification theory. The results show that, during the destructive test process, the T-beams experienced complete, partial linear, and non-linear stages. By using the equivalent stiffness and short-term stiffness to predict the stiffness changes during the overall failure process of the T-beams, it was found that, when cracks appeared, the stiffness of the T-beams decreased by 31% compared to the initial value, and the stiffness continued to decrease as the cracks extended further. The segmental stiffness system identification back-calculation method more accurately described the destructive test process of each section of the T-beams. This method can help to evaluate the extent of damage in each section of the beams during the overall destructive test process and further assess the overall structural integrity of the beams.

Objective To investigate the situation of carbapenem-resistant Enterobacteriaceae(CRE) colonization in patients undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Methods A total of 241 consecutive patients who underwent haplo-HSCT in the First Affiliated Hospital of Soochow University from June 1, 2021 to June 1, 2022 were enrolled. Anal swab screening was performed within 48 hours of admission and blood cultures were taken when the patient developed fever. Univariate and multivariate analysis were used to analyze the colonization rate, distribution, risk factors and the correlation between CRE colonization and post-transplant bloodstream infection(BSI). Results Among 241 patients with haplo-HSCT, there were 90 cases in CRE colonization positive group, with a colonization rate of 37.3% (90/241). Multivariate logistic regression analysis showed that sex (OR 2.42, 95% CI 1.38-4.22, P

PurposeTo investigate the value of quantitative longitudinal relaxation time (T1), transverse relaxation time (T2), and proton density (PD) maps derived from synthetic magnetic resonance imaging (MRI) for evaluating the status of lymphovascular space invasion (LVSI) in cervical squamous cell carcinoma (CSCC) without lymph node metastasis (LNM).Material and methodsPatients with suspected cervical cancer who visited our hospital from May 2020 to March 2023 were collected. All patients underwent preoperative MRI, including routine sequences and synthetic MRI. Patients with pathologically confirmed CSCC without lymphatic metastasis were included in this study. The subjects were divided into negative- and positive-LVSI groups based on the status of LVSI. Quantitative parameters of T1, T2, and PD values derived from synthetic MRI were compared between the two groups using independent samples t-test. Receiver operating characteristic curves were used to determine the diagnostic efficacy of the parameters.Results59 patients were enrolled in this study and were classified as positive (n = 32) and negative LVSI groups (n = 27). T1 and T2 values showed significant differences in differentiating negative-LVSI from positive-LVSI CSCC (1307.39 ± 122.02 vs. 1193.03 ± 107.86, P

ObjectivesTo compare the imaging quality, apparent diffusion coefficient (ADC), and the value of assessing bone marrow infiltration between reduced field-of-view diffusion-weighted imaging (r-FOV DWI) and conventional DWI in the lumbar spine of acute leukemia (AL).MethodsPatients with newly diagnosed AL were recruited and underwent both r-FOV DWI and conventional DWI in the lumbar spine. Two radiologists evaluated image quality scores using 5-Likert-type scales qualitatively and measured signal-to-noise ratio (SNR), contrast-to-noise (CNR), signal intensity ratio (SIR), and ADC quantitatively. Patients were divided into hypo- and normocellular group, moderately hypercellular group, and severely hypercellular group according to bone marrow cellularity (BMC) obtained from bone marrow biopsies. The image quality parameters and ADC value between the two sequences were compared. One-way analysis of variance followed by LSD post hoc test was used for the comparisons of the ADC values among the three groups. The performance of ADC obtained with r-FOV DWI (ADCr) and conventional DWI(ADCc) in evaluating BMC and their correlations with BMC and white blood cells (WBC) were analyzed and compared.Results71 AL patients (hypo- and normocellular: n=20; moderately hypercellular: n=19; severely hypercellular: n=32) were evaluated. The image quality scores, CNR, SIR, and ADC value of r-FOV DWI were significantly higher than those of conventional DWI (all p

Vascular fibrosis is a widespread pathologic condition that arises during vascular remodeling in cardiovascular dysfunctions. According to previous studies, vascular fibrosis is characterized by endothelial matrix deposition and vascular wall thickening. The RAAS and TGF-β/Smad signaling pathways have been frequently highlighted. It is, however, far from explicit in terms of understanding the cause and progression of vascular fibrosis. In this review, we collected and categorized a large number of molecules which influence the fibrosing process, in order to acquire a better understanding of vascular fibrosis, particularly of pathologic dysfunction. Furthermore, several mediators that prevent vascular fibrosis are discussed in depth in this review, with the aim that this will contribute to the future prevention and treatment of related conditions.

Diabetic kidney disease (DKD) is one of the severe complications of diabetes mellitus-related microvascular lesions, which remains the leading cause of end-stage kidney disease. The genesis and development of DKD is closely related to inflammation. Myeloid differentiation 2 (MD2) mediates hyperlyciemia-induced renal inflammation and DKD development and is considered as a potential therapeutic target of DKD. Here, we identified a new small-molecule MD2 inhibitor, JM-9. In vitro, JM-9 suppressed high glucose (HG) and palmitic acid (PA)-induced inflammation in MPMs, accompanied by inhibition of MD2 activation and the downstream TLR4/MyD88-MAPKs/NFκB pro-inflammatory signaling pathway. Macrophage-derived factors increased the fibrotic and inflammatory responses in renal tubular epithelial cells, which were inhibited by treating macrophages with JM-9. Then, we investigated the therapeutic effects against DKD in streptozotocin-induced type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) mouse models. Treatment with JM-9 prevented renal inflammation, fibrosis, and dysfunction by targeting MD2 in both T1DM and T2DM models. Our results show that JM-9, a new small-molecule MD2 inhibitor, protects against DKD by targeting MD2 and inhibiting MD2-mediated inflammation. In summary, JM-9 is a potential therapeutic agent for DKD.

The increasing penetration of renewables in power systems urgently entails the utilization of energy storage technologies. As the development of energy storage technologies depends highly on the profitability in electricity markets, to evaluate the economic potentials for various types of energy storage technologies under the comprehensive market environment is of great significance. To this end, this study aims at conducting a quantitative analysis on the economic potentials for typical energy storage technologies by establishing a joint clearing model for electric energy and ancillary service (AS) markets considering the operating features of energy storage systems (ESSs). Furthermore, a test system is adopted for numerical analysis that accurately represents for the real-world operation characteristics of power systems in China, with which the market prices, and operation schedules and profitability of ESSs are comparatively studied. The proposed methodology and results could provide beneficial references for the modifications on electricity markets and the development of ESSs towards the increasing penetration of renewables in power systems.

Abstract Normal karyotype acute myeloid leukemia (NK-AML) is a heterogeneous hematological malignancy that contains a minor population of self-renewing leukemia stem cells (LSCs), which complicate efforts to achieve long-term survival. We performed single-cell RNA sequencing to profile 39,288 cells from 6 bone marrow (BM) aspirates including 5 NK-AML (M4/M5) patients and 1 healthy donor. The single-cell transcriptome atlas and gene expression characteristics of each cell population in NK-AML (M4/M5) and healthy BM were obtained. In addition, we identified a distinct LSC-like cluster with possible biomarkers in NK-AML (M4/M5) and verified 6 genes using qRT‒PCR and bioinformatic analyses. In conclusion, we utilized single-cell technologies to provide an atlas of NK-AML (M4/M5) cell heterogeneity, composition, and biomarkers with implications for precision medicine and targeted therapies.

The grouting quality of prestressed pipelines directly affects the safety and durability of prestressed reinforced concrete bridge structures, attracting wide attention from the engineering community. Based on the principles of the scattering wave method, this paper designs and manufactures a large-scale model to simulate the actual construction testing environment. Several sets of design defects with significantly distributed spans in the prestressing ducts were pre-set, and the Engineering Geophysical Instrument System–Pipeline Grouting Profile (EGS-PGP) equipment developed was used to detect the grouting quality of the prestressed pipelines under different conditions, obtaining the frequency attenuation values at defect locations. The study shows that stability of the peak frequency throughout the test can indicate compact grouting, while a large fluctuation in the peak frequency range with no regular changes can indicate non-compact grouting; a sudden increase or decrease in peak frequency can effectively indicate the location of grouting defects along the pipeline. The number of sudden changes in frequency can indicate the number of gaps inside the pipeline. The chirp signal, compared to the hammer impact signal, shows greater stability and engineering application value in detecting defects using the scatter wave method. This study provides technical support for the detection of grouting quality in prestressed pipelines based on chirp signals.

Recently, the vascular protective effect of anti-diabetic agents has been receiving much attention. Sodium glucose cotransporter 2 (SGLT2) inhibitors had demonstrated reductions in cardiovascular (CV) events. However, the therapeutic effect of dapagliflozin on angiogenesis in peripheral arterial disease was unclear. This study aimed to explore the effect and mechanism of dapagliflozin on angiogenesis after hindlimb ischemia. We first evaluated the effect of dapagliflozin on post-ischemic angiogenesis in the hindlimbs of rats. Laser doppler imaging was used to detect the hindlimb blood perfusion. In addition, we used immunohistochemistry to detect the density of new capillaries after ischemia. The relevant signaling pathways of dapagliflozin affecting post-ischemic angiogenesis were screened through phosphoproteomic detection, and then the mechanism of dapagliflozin affecting post-ischemic angiogenesis was verified at the level of human umbilical vein endothelial cells (HUVECs). After subjection to excision of the left femoral artery, all rats were randomly distributed into two groups: the dapagliflozin group (left femoral artery resection, receiving intragastric feeding with dapagliflozin (1 mg/kg/d), for 21 consecutive days) and the model group, that is, the positive control group (left femoral artery resection, receiving intragastric feeding with citric acid–sodium citrate buffer solution (1 mg/kg/d), for 21 consecutive days). In addition, the control group, that is the negative control group (without left femoral artery resection, receiving intragastric feeding with citric acid–sodium citrate buffer solution (1 mg/kg/d), for 21 consecutive days) was added. At day 21 post-surgery, the dapagliflozin-treatment group had the greatest blood perfusion, accompanied by elevated capillary density. The results showed that dapagliflozin could promote angiogenesis after hindlimb ischemia. Then, the ischemic hindlimb adductor-muscle tissue samples from three rats of model group and dapagliflozin group were taken for phosphoproteomic testing. The results showed that the PI3K-Akt-eNOS signaling pathway was closely related to the effect of dapagliflozin on post-ischemic angiogenesis. Our study intended to verify this mechanism from the perspective of endothelial cells. In vitro, dapagliflozin enhanced the tube formation, migration, and proliferation of HUVECs under ischemic and hypoxic conditions. Additionally, the dapagliflozin administration upregulated the expression of angiogenic factors phosphorylated Akt (p-Akt) and phosphorylated endothelial nitric oxide synthase (p-eNOS), as well as vascular endothelial growth factor A (VEGFA), both in vivo and in vitro. These benefits could be blocked by either phosphoinositide 3-kinase (PI3K) or eNOS inhibitor. dapagliflozin could promote angiogenesis after ischemia. This effect might be achieved by promoting the activation of the PI3K-Akt-eNOS signaling pathway. This study provided a new perspective, new ideas, and a theoretical basis for the treatment of peripheral arterial disease.

This paper focuses on a heterogeneous redundant inertial navigation system (INS) that consists of one three-axis rotation-modulation fiber optic gyroscope (FOG) INS and one strapdown ring laser gyroscope (RLG) INS. A novel co-calibration method is proposed to estimate the FOG scale factor instability and RLG bias instability error in real time, in which the geometric constraints of the FOG-INS rotating axis are deployed to establish the observation equation without external reference information. In addition, the proposed method has a global navigation capability, which is achieved by using the normal vector of the earth ellipsoid and the state transformation extended Kalman filter to predict positioning errors. An output position error compensation method is used without disturbing the original INSs. Simulation and physical experiment results show that the positioning error of the heterogeneous redundant marine INS is reduced by more than 30% over 300 h of navigation.

Background: The roles of Connexin43 (Cx43) in clear cell renal cell carcinoma (ccRCC) microenviroment remains to be poorly defined. Methods: The expression profile, prognosis and immune analysis of Cx43 in various cancers, particularly in ccRCC were performed using TCGA database, and various biological function assays were applied to explore the physiological role of Cx43 and tangeretin in ccRCC. Western blot were applied to examine the protein expression and Kunming mice were used to evaluate preliminary safety or anti-tumor activity of tangeretin and sunitinib. Results: Compared with the normal group, higher expression levels of Cx43 in ccRCC, and distinct associations between Cx43 expression and ccRCC prognosis or immune infiltration, were found. Notably, the expression of Cx43 was found to be highly correlated with that of receptor tyrosine kinases (RTKs), particularly with VEGFR1, VEGFR2 and VEGFR3. The expression of Cx43 and EGFR was also found to be higher in ccRCC than that in the para-cancerous specimens. Knocking down Cx43 expression decreased RCC cell viability, cell migration, p-EGFR, MMP-9 and survivin expression. Using 14 Chinese medicine monomers, tangeretin was screened and found to inhibit tumor cell viability and Cx43 expression. Tangeretin also enhanced the sensitivity of RCC cells to tyrosine kinase inhibitors (TKIs) sunitinib and sorafenib. However, the same concentration of tangeretin exerted a less prominent effect on normal renal cell viability. Conclusions: Cx43 is strongly associated with RTK expression and ccRCC progression, while tangeretin can inhibit RCC cell malignancy by inhibiting Cx43 expression and enhance the sensitivity of RCC cells to TKIs.

Objective: Indocyanine green (ICG) with near-infrared fluorescence absorption is approved by the United States Food and Drug Administration for clinical applications in angiography, blood flow evaluation, and liver function assessment. It has strong optical absorption in the near-infrared region, where light can penetrate deepest into biological tissue. We sought to review its value in guiding prostate cancer treatment. Methods: All related literature at PubMed from January 2000 to December 2020 were reviewed. Results: Multiple preclinical studies have demonstrated the usefulness of ICG in identifying prostate cancer by using different engineering techniques. Clinical studies have demonstrated the usefulness of ICG in guiding sentinel node dissection during radical prostatectomy, and possible better preservation of neurovascular bundle by identifying landmark prostatic arteries. New techniques such as adding fluorescein in additional to ICG were tested in a limited number of patients with encouraging result. In addition, the use of the ICG was shown to be safe. Even though there are encouraging results, it does not carry sufficient sensitivity and specificity in replacing extended pelvic lymph node dissection during radical prostatectomy. Conclusion: Multiple preclinical and clinical studies have shown the usefulness of ICG in identifying and guiding treatment for prostate cancer. Larger randomized prospective studies are warranted to further test its usefulness and find new modified approaches.

Objectives: The study aimed to evaluate quality of nephrolithometric nomograms to predict stone-free rates (SFRs) and complication rates (CRs) in case of minimally invasive percutaneous nephrolithotomy (PNL). In the last decade, nomograms have been introduced to estimate the SFRs and CRs of PNL. However, no data are available regarding their reliability in case of utilization of miniaturized devices. Herein we present a prospective multicentric study to evaluate reliability of Guy’s stone score (GSS), the stone size, tract length, obstruction, number of involved calyces, and essence of stone (S.T.O.N.E.) nephrolithometry score and Clinical Research Office of the Endourological Society (CROES) score in patients treated with minimally invasive PNL. Methods: We evaluated SFRs and CRs of 222 adult patients treated with miniaturized PNL. Patients were considered stone-free if no residual fragments of any size at post-operative unenhanced computed tomography scan. Patients demographics, SFRs, and CRs were reported and analyzed. Performances of nomograms were evaluated with the area under the curve (AUC). Results: We included 222 patients, the AUCs of GSS, CROES score, and S.T.O.N.E. nephrolithometry score were 0.69 (95% confidence interval [CI] 0.61–0.78), 0.64 (95% CI 0.56–0.73), and 0.62 (95% CI 0.52–0.71), respectively. Regarding SFRs, at multivariate binomial logistic regression, only the GSS had significance with an odds ratio of 0.53 (95% CI 0.31–0.95, p=0.04). We did not find significant correlation with complications, with only a trend for GSS. Conclusion: This is the first study evaluating nomograms in miniaturized PNL. They still show good reliability; however, our data showed lower performances compared to standard PNL. We emphasize the need of further studies to confirm this trend. A dedicated nomogram for minimally invasive PNL may be necessary.

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.

BackgroundRecently emerged reports indicated that patients with coronavirus disease 2019 (COVID-19) might experience novo genitourinary symptoms after discharge. Nevertheless, the causal associations and underlying mechanisms remain largely unclear.MethodsGenome-wide association study (GWAS) statistics for COVID-19 and 28 genitourinary symptoms with consistent definitions were collected from the COVID‐19 Host Genetic Initiative, FinnGen, and UK Biobanks. Mendelian randomization (MR) analyses were applied to explore the causal effects of COVID-19 on genitourinary symptoms by selecting single-nucleotide polymorphisms as instrumental variables. Meta-analyses were conducted to evaluate the combined causal effect. Molecular pathways connecting COVID-19 and its associated disorders were evaluated by weighted gene co-expression network analysis (WGCNA) and enrichment analyses to extract insights into the potential mechanisms underlying the connection.ResultsThe MR and meta-analyses indicated that COVID-19 was causally associated with increased risk for calculus of the lower urinary tract (LUTC, OR: 1.2984 per doubling in odds of COVID‐19, 95% CI: 1.0752–1.5680, p = 0.007) and sexual dysfunction (SD, OR: 1.0931, 95% CI: 1.0292–1.1610, p = 0.004). Intriguingly, COVID-19 might exert a slight causal protective effect on the progression of urinary tract infections (UTIs) and bladder cancer (BLCA). These results were robust to sensitivity analyses. Bioinformatic analyses indicated that the inflammatory-immune response module may mediate the links between COVID‐19 and its associated disorders at the molecular level.ConclusionsIn response to post-COVID-19 symptoms, we recommend that COVID-19 patients should strengthen the prevention of LUTC and the monitoring of sexual function. Meanwhile, the positive effects of COVID-19 on UTIs and BLCA should attach equal importance.

Abstract Background Correct perioperative antibiotic strategies are crucial to prevent postoperative infections during percutaneous nephrolithotomy (PCNL). We aimed to compare the realistic antibiotic strategies applied in China with current urological guidelines. Methods Between April and May 2020, urologists from China were invited to finish an online cross-sectional survey. The questionnaire was designed according to the current urological guidelines and literatures. Results 3393 completed responses were received. 61.1% (2073/3393) respondents had urological experience of more than 10 years. 72.4% urologists chose multiple-dose antibiotics for patients with both negative urine culture (UC-) and negative urine microscopy (UM-) preoperatively. Respondents in central China (OR = 1.518; 95% CI 1.102–2.092; P = 0.011), east China (OR = 1.528; 95% CI 1.179–1.979; P = 0.001) and northeast China (OR = 1.904; 95% CI 1.298–2.792; P = 0.001) were more likely to prescribe multiple-dose antibiotic for UC-UM- patients. Notably, the respondents who finished PCNL exceeded 100 cases per year were in favor of single-dose administration (OR = 0.674; 95% CI 0.519–0.875; P = 0.003). There are only 8.3% urologists chose single-dose antibiotic for UC-UM+ patients, whereas 65.5% administered antibiotics for 1–3 days. Meanwhile, for UC+ patients, 59.0% of the urologists applied antibiotics shorter than 1 week, and only 26.3% of the urologists carried out routine re-examination of UC. Moreover, postoperative antibiotics were frequently prescribed for 3–6 days (1815; 53.5%). Finally, although 88.2% urologists considered stone culture important for management of postoperative antibiotics as the guideline recommended, only 18.5% performed it routinely. Conclusions The antibiotic strategies are different between current practice in China and the urological guidelines. The dissimilarities suggested that further studies should be conducted to investigate the reasons of the differences and standardize the application of antibiotics.

Background: Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous disease with a complicated prognosis. Even though various prognostic evaluations have been applied currently, they usually only use the clinical factors that overlook the molecular underlying DLBCL progression. Therefore, more accurate prognostic assessment needs further exploration. In the present study, we constructed a novel prognostic model based on microtubule associated genes (MAGs).Methods: A total of 33 normal controls and 1360 DLBCL samples containing gene-expression from the Gene Expression Omnibus (GEO) database were included. Subsequently, the univariate Cox, the least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis were used to select the best prognosis related genes into the MAGs model. To validate the model, Kaplan-Meier curve, and nomogram were analyzed.Results: A risk score model based on fourteen candidate MAGs (CCDC78, CD300LG, CTAG2, DYNLL2, MAPKAPK2, MREG, NME8, PGK2, RALBP1, SIGLEC1, SLC1A1, SLC39A12, TMEM63A, and WRAP73) was established. The K-M curve presented that the high-risk patients had a significantly inferior overall survival (OS) time compared to low-risk patients in training and validation datasets. Furthermore, knocking-out TMEM63A, a key gene belonging to the MAGs model, inhibited cell proliferation noticeably.Conclusion: The novel MAGs prognostic model has a well predictive capability, which may as a supplement for the current assessments. Furthermore, candidate TMEM63A gene has therapeutic target potentially in DLBCL.

BackgroundWe aimed to compare the efficacy of chimeric antigen receptor T (CAR-T) cell therapy with that of autologous stem cell transplantation (auto-HSCT) in relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL).Research design and methodsWe searched eligible publications up to January 31st, 2022, in PubMed, Cochrane Library, Springer, and Scopus. A total of 16 publications with 3484 patients were independently evaluated and analyzed using STATA SE software.ResultsPatients who underwent CAR-T cell therapy showed a better overall response rate (ORR) and partial response (PR) than those treated with auto-HSCT (CAR-T vs. auto-HSCT, ORR: 80% vs. 73%, HR:0.90,95%CI:0.76-1.07,P = 0.001; PR: 20% vs. 14%, HR:0.65,95%CI:0.62-0.68,P = 0.034). No significant difference was observed in 6-month overall survival (OS) (CAR-T vs. auto-HSCT, six-month OS: 81% vs. 84%, HR:1.23,95%CI:0.63-2.38, P = 0.299), while auto-HSCT showed a favorable 1 and 2-year OS (CAR-T vs. auto-HSCT, one-year OS: 64% vs. 73%, HR:2.42,95%CI:2.27-2.79, P < 0.001; two-year OS: 54% vs. 68%, HR:1.81,95%CI:1.78-1.97, P < 0.001). Auto-HSCT also had advantages in progression-free survival (PFS) (CAR-T vs. auto-HSCT, six-month PFS: 53% vs. 76%, HR:2.81,95%CI:2.53-3.11,P < 0.001; one-year PFS: 46% vs. 61%, HR:1.84,95%CI:1.72-1.97,P < 0.001; two-year PFS: 42% vs. 54%, HR:1.62,95%CI:1.53-1.71, P < 0.001). Subgroup analysis by age, prior lines of therapy, and ECOG scores was performed to compare the efficacy of both treatment modalities.ConclusionAlthough CAR-T cell therapy showed a beneficial ORR, auto-HSCT exhibited a better long-term treatment superiority in R/R DLBCL patients. Survival outcomes were consistent across different subgroups.

Faba bean (Vicia faba L.) is an important food and feed legume crop in the world. The root rot complex caused by various pathogens is a main constraint in faba bean production. In April 2021, a severe disease of faba bean with symptoms of black necrosis on roots occurred in experimental fields at the Linxia Institute of Agricultural Sciences, Gansu Province, China. This study aimed to identify the pathogen and evaluate the resistance of faba bean cultivars. The pathogen was isolated from infected soils, and five representative isolates were identified as Berkeleyomyces rouxiae based on morphological characteristics, pathogenicity, and molecular phylogenetic analyses. A host range test showed that chickpea, common bean, cowpea, mung bean, rice bean, lentil, and hyacinth bean were susceptible hosts of the faba bean isolate, whereas adzuki bean, pea, and soybean were non-susceptible hosts, and maize and wheat were non-hosts. Identification of resistance among 36 faba bean cultivars was carried out, and six cultivars were found to be moderately resistant to B. rouxiae. In this study, we first reported black root rot on faba bean caused by B. rouxiae, confirmed and expanded the host range of B. rouxiae, and identified resistant faba bean cultivars.

Bone marrow is one of the most important organs in the human body. The evaluation of bone marrow microstructure and gender-related cellular and capillary networks in healthy young adults can help to better understand the process of bone metabolism. Intravoxel incoherent motion (IVIM) provides both diffusion and perfusion quantifications without requiring intravenous contrast agent injection. In this prospective study, 60 healthy young age-matched volunteers (30 men and 30 women) underwent MRI scans at 1.5 T using multi–b-value diffusion-weighted imaging on sagittal planes covering the lumbar bone marrow. The apparent diffusion coefficient (ADC), true ADC (D), pseudo-ADC (D*), and perfusion fraction (f) were calculated from the diffusion-weighted images using the mono- and bi-exponential models. Lumbar cancellous bone (L2–L4) was selected as the region of interest. An independent t-test was used to detect significant differences in ADC values and IVIM parameters between men and women. The differences in IVIM parameters among the L2, L3, and L4 groups were compared with analysis of variance. The D and f values in women were significantly higher than that in men (p = 0.001, 0.026). However, D* was significantly lower in women than that in men (p = 0.001). Furthermore, there was no significant gender difference for the conventional ADC value (p = 0.186). Moreover, there were no significant differences in the D, f, and D* values among the L2, L3, and L4 vertebras of women or men. IVIM parameters can show differences in bone marrow between young women and men. As a non-invasive method, it can assess bone marrow microstructure, such as cellularity and perfusion.

BackgroundA thoracogastric airway fistula (TGAF) is a rare and potentially fatal complication of esophagectomy for esophageal and cardia carcinomas. Isolation of the fistula and pulmonary separation is necessary during the surgical repair of a tracheal fistula. However, currently, the reported airway management techniques are not suitable for patients with a large TGAF. This case study presents an alternative technique for performing differential lung ventilation in a patient with a thoracogastric airway fistula.Case presentationA 70-year-old man was diagnosed with a thoracogastric airway fistula situated above the carina after esophagectomy, and a thoracoscope-assisted repair of the fistula and pectoralis major myocutaneous flap transplantation were scheduled. The patient could not tolerate one-lung ventilation and the complex intubating operation due to aspiration pneumonia and the size (3.5 cm × 1.7 cm) of the fistula. We, therefore, performed differential lung ventilation in which an extended 6.5#single-lumen endotracheal tube was inserted into the left main bronchus and a 9Fr bronchial blocker was placed in the right main bronchus by using the video-flexible intubation scope. The right lung was selectively inflated with jet ventilation, while positive pressure ventilation was maintained through the left endotracheal tube. The value of SPO2 remained above 95% throughout the operation.ConclusionFor patients with a large thoracogastric airway fistula, differential lung ventilation of a combination of positive pressure ventilation and jet ventilation is useful. Inserting an extended single-lumen endotracheal tube into the left main bronchus and a bronchial blocker into the right main bronchus could be another way of providing differential ventilation for patients with a large thoracogastric airway fistula.

Due to the molecular heterogeneity, most bladder cancer (BLCA) patients show no pathological responses to immunotherapy and chemotherapy yet suffer from their toxicity. This study identified and validated three distinct and stable molecular clusters of BLCA in cross-platform databases based on personalized immune and inflammatory characteristics. H&E-stained histopathology images confirmed the distinct infiltration of immune and inflammatory cells among clusters. Cluster-A was characterized by a favorable prognosis and low immune and inflammatory infiltration but showed the highest abundance of prognosis-related favorable immune cell and inflammatory activity. Cluster-B featured the worst prognosis and high immune infiltration, but numerous unfavorable immune cells exist. Cluster-C had a favorable prognosis and the highest immune and inflammatory infiltration. Based on machine learning, a highly precise predictive model (immune and inflammatory responses signature, IIRS), including FN1, IL10, MYC, CD247, and TLR2, was developed and validated to identify the high IIRS-score group that had a poor prognosis and advanced clinical characteristics. Compared to other published models, IIRS showed the highest AUC in 5 years of overall survival (OS) and a favorable predictive value in predicting 1- and 3- year OS. Moreover, IIRS showed an excellent performance in predicting immunotherapy and chemotherapy’s response. According to immunohistochemistry and qRT-PCR, IIRS genes were differentially expressed between tumor tissues with corresponding normal or adjacent tissues. Finally, immunohistochemical and H&E-stained analyses were performed on the bladder tissues of 13 BLCA patients to further demonstrate that the IIRS score is a valid substitute for IIR patterns and can contribute to identifying patients with poor clinical and histopathology characteristics. In conclusion, we established a novel IIRS depicting an IIR pattern that could independently predict OS and acts as a highly precise predictive biomarker for advanced clinical characters and the responses to immunotherapy and chemotherapy.

Fusarium ear rot (FER) caused by Fusarium verticillioides is a prevalent maize disease. To comprehensively characterize the genetic basis of the natural variation in FER resistance, a recombinant inbred line (RIL) population was used to map quantitative trait loci (QTL) for FER resistance. A total of 17 QTL were identified by linkage mapping in eight environments. These QTL were located on six chromosomes and explained 3.88–15.62% of the total phenotypic variation. Moreover, qFER1.03 had the strongest effect and accounted for 4.98–15.62% of the phenotypic variation according to analyses of multiple environments involving best linear unbiased predictions. The chromosome segment substitution lines (CSSLs) derived from a cross between Qi319 (donor parent) and Ye478 (recurrent parent) were used to verify the contribution of qFER1.03 to FER resistance. The line CL171, which harbored an introgressed qFER1.03, was significantly resistant to FER. Further fine mapping of qFER1.03 revealed that the resistance QTL was linked to insertion/deletion markers InDel 8 and InDel 2, with physical distances of 43.55 Mb and 43.76 Mb, respectively. Additionally, qFER1.03 differed from the previous resistance QTL on chromosome 1. There were three annotated genes in this region. On the basis of the RNA-seq data, which revealed the genes differentially expressed between the FER-resistant Qi319 and susceptible Ye478, GRMZM2G017792 (MPK3) was preliminarily identified as a candidate gene in the qFER1.03 region. The Pr-CMV-VIGS system was used to decrease the GRMZM2G017792 expression level in CL171 by 34–57%, which led to a significant decrease in FER resistance. Using RIL and CSSL populations combined with RNA-seq and Pr-CMV-VIGS, the candidate gene can be dissected effectively, which provided important gene resource for breeding FER-resistant varieties.

Overactive bladder (OAB) is the most bothersome symptom in lower urinary tract symptoms (LUTS). Current pharmacologic treatment aims to inhibit detrusor contraction; however, shows unsatisfied efficacy and high discontinuation rate. LIM kinases (LIMKs) promote smooth muscle contraction in the prostate; however, their function in the bladder smooth muscle remains unclear. Here, we studied effects of the LIMK inhibitors on bladder smooth muscle contraction and proliferation both in vitro and in vivo experiments. Bladder expressions of LIMKs are elevated in OAB rat detrusor tissues. Two LIMK inhibitors, SR7826 and LIMKi3, inhibit contraction of human detrusor strip, and cause actin filament breakdown, as well as cell proliferation reduction in cultured human bladder smooth muscle cells (HBSMCs), paralleled by reduced cofilin phosphorylation. Silencing of LIMK1 and LIMK2 in HBSMCs resulted in breakdown of actin filaments and decreased cell proliferation. Treatment with SR7826 or LIMKi3 decreased micturition frequency and bladder detrusor hypertrophy in rats with bladder outlet obstruction. Our study suggests that LIMKs may promote contraction and proliferation in the bladder smooth muscle, which could be inhibited by small molecule LIMK inhibitors. LIMK inhibitors could be a potential therapeutic strategy for OAB- related LUTS.

Abstract. Fanconi anemia (FA), an X-linked genetic or autosomal recessive disease, exhibits complicated pathogenesis. Previously, we detected the mutated Dynein Axonemal Heavy Chain 2 (DNAH2) gene in 2 FA cases. Herein, we further investigated the potential association between DNAH2 and the homologous recombination repair pathway of FA. The assays of homologous recombination repair, mitomycin C (MMC) sensitivity, immunofluorescence, and ubiquitination modification were performed in U2OS and DR-U2OS cell lines. In MMC-treated U2OS cells, the downregulation of the DNAH2 gene increased the sensitivity of cells to DNA inter-strand crosslinks. We also observed the reduced enrichment of FANCD2 protein to DNA damage sites. Furthermore, the ubiquitination modification level of FANCD2 was influenced by the deficiency of DNAH2. Thus, our results suggest that DNAH2 may modulate the cell homologous recombination repair partially by increasing the ubiquitination and the enrichment to DNA damage sites of FANCD2. DNAH2 may act as a novel co-pathogenic gene of FA patients.

Diffuse large B cell lymphoma (DLBCL) exhibits a tightly complexity immune landscape. In this study, we intended to identify different immune phenotype and to examine the immune related mRNA signature for clinical characteristic, therapeutic responsiveness as well as risk stratification and survival prediction in DLBCL. We identified two immune infiltration subtypes of DLBCL patients based on 28 immune cell types. GSEA analysis uncovered the concordant classification of two robust significant subtypes of DLBCL. Considering the convenient application of the immune infiltration subtypes for prognostic prediction, we developed a risk score based on the differentially expressed genes between the Immunity-H and Immunity-L groups. By a least absolute shrinkage and selection operator (LASSO)-Cox regression model, a sixteen-gene risk signature, comprising ANTXR1, CD3D, TIMP1, FPR3, NID2, CTLA4, LPAR6, GPR183, LYZ, PTGDS, ITK, FBN1, FRMD6, PLAU, MICAL2, C1S, was established. The comprehensive results showed that the high-risk group was correlated with lower immune infiltration, more aggressive phenotypes, lower overall survival and more sensitive to lenalidomide. In contrast, a low-risk group score was associated with higher immune infiltration, less aggressive phenotypes, better overall survival and more likely to benefit from PD-1/PD-L1 inhibitors. Finally, a nomogram comprised of the risk score and IPI score was verified to more accurately predict the overall survival of DLBCL than traditional clinical prediction models. Altogether, our data demonstrate the heterogeneity of immune patterns within DLBCL and deepen our molecular understanding of this tumor entity.

Background: Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous disease that can have profound differences in survival outcomes. A variety of powerful prognostic factors and models have been constructed; however, the development of more accurate prognosis prediction and targeted treatment for DLBCL still faces challenges. An explosion of research on super-enhancer (SE)–associated genes provide the possibility to use in prognostication for cancer patients. Here, we aimed to establish a novel effective prognostic model using SE-associated genes from DLBCL.Methods: A total of 1,105 DLBCL patients from the Gene Expression Omnibus database were included in this study and were divided into a training set and a validation set. A total of 11 SE-associated genes (BCL2, SPAG16, PXK, BTG1, LRRC37A2, EXT1, TGFBR2, ANKRD12, MYCBP2, PAX5, and MYC) were initially screened and identified by the least absolute shrinkage and selection operator (Lasso) penalized Cox regression, univariate and multivariate Cox regression analysis. Finally, a risk score model based on these 11 genes was constructed.Results: Kaplan–Meier (K–M) curves showed that the low-risk group appeared to have better clinical survival outcomes. The excellent performance of the model was determined via time-dependent receiver operating characteristic (ROC) curves. A nomogram based on the polygenic risk score was further established to promote reliable prognostic prediction. This study proposed that the SE-associated-gene risk signature can effectively predict the response to chemotherapy in DLBCL patients.Conclusion: A novel and reliable SE-associated-gene signature that can effectively classify DLBCL patients into high-risk and low-risk groups in terms of overall survival was developed, which may assist clinicians in the treatment of DLBCL.

Cold is an abiotic stress that can greatly affect the growth and survival of plants. Here, we reported that an AP2/ERF family gene, BplERF1, isolated from Betula platyphylla played a contributing role in cold stress tolerance. Overexpression of BplERF1 in B. platyphylla transgenic lines enhanced cold stress tolerance by increasing the scavenging capability and reducing H2O2 and malondialdehyde (MDA) content in transgenic plants. Construction of BplERF-mediated multilayered hierarchical gene regulatory network (ML-hGRN), using Top-down GGM algorithm and the transcriptomic data of BplERF1 overexpression lines, led to the identification of five candidate target genes of BplERF1 which include MPK20, ERF9, WRKY53, WRKY70, and GIA1. All of them were then verified to be the true target genes of BplERF1 by chromatin-immunoprecipitation PCR (ChIP-PCR) assay. Our results indicate that BplERF1 is a positive regulator of cold tolerance and is capable of exerting regulation on the expression of cold signaling and regulatory genes, causing mitigation of reactive oxygen species.

Abstract Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis and the abnormal differentiation of hematopoietic stem cells. An increasing number of researches have demonstrated that microRNAs play crucial roles in the pathogenesis of myelodysplastic syndromes. Herein, we aimed to identify novel potential microRNAs bound up with the diagnosis and prognosis of MDS. MiRNA microarray analysis was used to screen deregulated microRNAs in the bone marrow of MDS patients. qRT-PCR was employed to confirm the microarray results. All members of miR-320 family (miR-320a, miR-320b, miR-320c, miR-320d, and miR-320e) were significantly increased in MDS patients compared to normal control. Although we found no correlation between miR-320 family and most clinical characteristics, high miR-320c and miR-320d expression seemed to be associated with high numbers of bone marrow (BM) blasts and worse karyotype. High expression of all the members of the miR-320 family seemed to be associated with a high prognostic score based on International Prognostic Scoring System (IPSS). The areas under the miR-320 family member ROC curves were 0.9037 (P

Objective: To assess the relevance of urine test (UT), urine culture (UC) and stone culture (SC) for postoperative infections and to investigate the optimal perioperative antibiotic treatment strategy in association with percutaneous nephrolithotomy (PCNL) in patients with renal calculi. Materials and methods: Between September 2016 and September 2018 1,060 patients treated with PCNL were included in the study. The results of UT, UC and SC were reviewed. The details of perioperatively administered antibiotics and postoperative infections were recorded. Results: A positive UT was associated with an increased incidence of infection; this was also the case in patients with negative UC (p < 0.05). There was no significant difference in incidence of infection between patients who were given a single dose of antibiotics compared with those given multiple doses when UC was negative, whether UT was positive or negative (all p > 0.05). The incidence of infection was decreased when pre-operative antibiotics were administered according to the sensitivity pattern based on UC (p < 0.05). This outcome was particularly evident when the treatment duration exceeded 7 days (p < 0.05). A positive SC was associated with increased incidence of infection, even if the patient had a negative UC and UT (p < 0.05). The incidence of infection was significantly decreased when antibiotic treatment was administered based on the results of SC (p < 0.05). Conclusion: Pre-operative prophylaxis with a single-dose antibiotic was sufficient in patients with negative UC, whether UT was positive or negative. Pre-operative treatment with antibiotics according to the bacterial sensitivity pattern should be administered for ≥7 days in patients with positive UC. The postoperative antibiotic treatment strategy should be tailored according to the SC results.

Abstract Background Upper urinary tract stones is the most common diseases in urology. Percutaneous nephrolithotomy (PCNL) and ureteroscopic lithotripsy (fURL) are common treatment, but both their efficacy and safety are controversial. Thus we aim to evaluate the efficacy and safety of PCNL and fURL in the treatment of upper urinary tract stones, providing a reference for clinical work. Methods PubMed, Web of Science, Embase and CNKI were searched through Apr. 1, 2019 to identify eligible studies. Data were analyzed by using RevMan 5.3 and Stata 12.0 software. Pooled relative risks (RRs) or weighted mean difference (WMD) with 95% confidence intervals (CIs) were calculated using fixed or random effects methods. Publication bias and sensitivity analysis were performed. Results Four randomized controlled trials (RCTs), fifteen cohort studies involving 1822 patients were included. Stone-free rate of PCNL was significantly high than that of fURL (RR: 1.07; 95% CI: 1.03, 1.12; P = 0.0004). The decline of hemoglobin in PCNL was significantly high than that of fURL (WMD: 1.07; 95% CI: 0.54, 1.61; P

Abstract Background Although major driver gene have been identified, the complex molecular heterogeneity of renal cell cancer (RCC) remains unclear. Therefore, more relevant genes need to be identified to explain the pathogenesis of renal cancer. Methods Microarray datasets GSE781, GSE6344, GSE53000 and GSE68417 were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified by employing GEO2R tool, and function enrichment analyses were performed by using DAVID. The protein-protein interaction network (PPI) was constructed and the module analysis was performed using STRING and Cytoscape. Survival analysis was performed using GEPIA. Differential expression was verified in Oncomine. Cell experiments (cell viability assays, transwell migration and invasion assays, wound healing assay, flow cytometry) were utilized to verify the roles of the hub genes on the proliferation of kidney cancer cells (A498 and OSRC-2 cell lines). Results A total of 215 DEGs were identified from four datasets. Six hub gene (SUCLG1, PCK2, GLDC, SLC12A1, ATP1A1, PDHA1) were identified and the overall survival time of patients with RCC were significantly shorter. The expression levels of these six genes were significantly decreased in six RCC cell lines(A498, OSRC-2, 786- O, Caki-1, ACHN, 769-P) compared to 293t cell line. The expression level of both mRNA and protein of these genes were downregulated in RCC samples compared to those in paracancerous normal tissues. Cell viability assays showed that overexpressions of SUCLG1, PCK2, GLDC significantly decreased proliferation of RCC. Transwell migration, invasion, wound healing assay showed overexpression of three genes(SUCLG1, PCK2, GLDC) significantly inhibited the migration, invasion of RCC. Flow cytometry analysis showed that overexpression of three genes(SUCLG1, PCK2, GLDC) induced G1/S/G2 phase arrest of RCC cells. Conclusion Based on our current findings, it is concluded that SUCLG1, PCK2, GLDC may serve as a potential prognostic marker of RCC.

Coptis chinensis Franch (CCF) is extensively used in the treatment of inflammatory-related diseases. Accumulating studies have previously demonstrated the anti-inflammatory properties of CCF, yet data on its exact targets against urinary tract infections (UTIs) remain largely unknown. Therefore, the present study decodes the potential targets of action of CCF against UTIs by network pharmacology combined with experiment evaluations. Based on the pharmacology network analysis, the current study yielded six core ingredients: quercetin, palmatine (R)-canadine, berlambine, berberine, and berberrubine. The protein–protein interaction network (PPI) was generated by the string database, and then, four targets (IL6, FOS, MYC, and EGFR) were perceived as the major CCF targets using the CytoNCA plug-in. The results of molecular docking showed that the six core constituents of CCF had strong binding affinities toward the four key targets of UTIs after docking into the crystal structure. The enrichment analysis indicated that the possible regulatory mechanisms of CCF against UTIs were based on the modules of inflammation, immune responses, and apoptosis among others. Experimentally, the Escherichia coli (E. coli) strain CFT073 was applied to establish in vivo and in vitro models. In vivo results revealed that the key targets, IL6 and FOS, are significantly upregulated in rat bladder tissues of UTIs, whereas the expression of MYC and EGFR remained steady. Last, in vitro results further confirmed the therapeutic potential of CCF by reducing the expression of IL6 and FOS. In conclusion, IL6 and FOS were generally upregulated in the progression of E. coli–induced UTIs, whereas the CCF intervention exerted a preventive role in host cells stimulated by E. coli, partially due to inhibiting the expression of IL6 and FOS.

As semiconductor technology evolves, computing platforms attempt to integrate hundreds of processing cores and associated interconnects into a single chip. Network-on-chip (NoC) technology has been widely used for data exchange centers in recent years. As the core element of the NoC, the round-robin arbiter provides fair and fast arbitration, which is essential to ensure the high performance of each module on the chip. In this paper, we propose a low-latency fair switch arbiter (FSA) architecture based on the tree structure search algorithm. The FSA uses a feedback-based parallel priority update mechanism to complete the arbitration within the leaf nodes and a lock-based round-robin search algorithm to guarantee global fairness. To reduce latency, the FSA keeps the lock structure only at the leaf node so that the complexity of the critical path does not increase. Meanwhile, the FSA achieves a critical path with only O(log4N) delay by using four input nodes in parallel. The latency of the proposed circuit is on average 22.2% better than the existing fair structures and 8.1% better than the fastest arbiter, according to the synthesis results. The proposed architecture is well suited for high-speed network-on-chip switches and has better scalability for switches with large numbers of ports.