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Strain‒induced precipitation is a characteristic physical‒metallurgical phenomenon during hot‒rolling in microalloyed steel production that strongly affects the overallthermomechanical control process. In this study, the strain‒induced precipitation behavior in titanium‒molybdenum microalloyed steel was comprehensively investigated, and its complex effects on the austenite/ferrite transformation during continuous cooling were analyzed for the first time, based on stress relaxation and multi‒aspect characterization methods. The stress relaxation results revealed that the fastest strain‒induced precipitation occurred at 900 °C. The precipitates were identified as FCC structured (Ti, Mo)C particles with a coherent or semi‒coherent cubic‒cubic orientation relationship to the austenite matrix. The strain‒induced precipitation proved to increase the ferrite transformation temperature and proportion, significantly refine and homogenize the transformed grains. The intermittent quenching at 0.5 C/s further revealed that the (Ti, Mo)C particles with cubic‒cubic orientation relationship to austenite matrix exerted a dual pinning effect: by pinning dislocations, these particles facilitated diffusion‒controlled ferrite nucleation and growth both at austenite grain boundaries and within grains; by pinning migrating phase interfaces, the particles inhibited the coarsening of ferrite grains. Coupled with compressive testing and strengthening contribution analysis, the strain‒induced precipitation was shown to weaken precipitation strengthening but enhance grain refinement strengthening, thereby providing a novel approach to achieving an optimal balance between microstructural homogeneity and mechanical properties.

Abstract Background Fibroblast growth factors (FGFs) are cell signaling proteins that perform multiple biological processes in many biological processes (cell development, repair, and metabolism). The dynamics of tumor cells, such as angiogenesis, transformation, and proliferation, have a significant impact on neoplasia and are modulated by FGFs. FGFs’ expression and prognostic significance in ovarian cancer (OC), however, remain unclear. Methods Through a series of in silico analysis, we investigated the transcriptional, survival data, genetic variation, gene-gene interaction network, ferroptosis-related genes, and DNA methylation of FGFs in OC patients. Results We discovered that while FGF18 expression levels were higher in OC tissues than in normal OC tissues, FGF2/7/10/17/22 expression levels were lower in the former, and that FGF1/19 expression was related to the tumor stage in OC patients. According to the survival analysis, the clinical prognosis of individuals with OC was associated with the aberrant expression of FGFs. The function of FGFs and their neighboring genes was mainly connected to the cellular response to FGF stimulus. There was a negative correlation between FGF expression and various immune cell infiltration. Conclusions This study clarifies the relationship between FGFs and OC, which might provide new insights into the choice of prognostic biomarkers of OC patients.

The glycosyl hydrolase β-glucanase elicits plant immune responses against pathogens and enhances plant immunity by activating signaling pathways. The specific functional domains responsible for disease prevention remain unclear. In this study, transient expression of β-glucanase significantly increased leaves resistance to Botrytis cinerea in Nicotiana benthamiana systemic leaves. Through sequence alignment and similarity analysis, five conserved motifs in the amino acid sequence of β-glucanase were identified, and five deletion mutants were generated to investigate its essential regions further. Notably, the N-terminal amino acid sites 5-54 deletion mutation of β-glucanase decreased resistance to B. cinerea infection. These results indicate that N-terminal amino acids 5-54 (N54) are crucial for β-glucanase induced N. benthamiana defense response and for enhancing resistance to B. cinerea. Further analysis using real-time quantitative fluorescent PCR (qRT-PCR) revealed a significant reduction in gene expression within the N54 region compared to that of unmutated β-glucanase. Additionally, there was a notable reduction in the relative expression levels of FRK, CYP71D20, WRKY7, WRKY8, ACRE31 and PTI genes. Therefore, the first 50 amino acids at positions 5-54 within the N-terminal domain were essential for triggering plant defense responses and enhancing resistance against B. cinerea infection. This study provides an important theoretical foundation for systematic investigation into key functional domains within β-glucanase that trigger defensive responses in plants against B. cinerea.

Abstract Background This study aimed to evaluate the efficiency of hippocampal avoidance whole-brain radiotherapy with a simultaneous integrated boost (HA-WBRT-SIB) treating brain metastases (BM) and utility of the Hopkins Verbal Learning Test-Revised (HVLT-R) (Chinese version) in Chinese lung cancer patients. Methods Lung cancer patients with BM undergone HA-WBRT-SIB at our center were enrolled. Brain magnetic resonance imaging, The HVLT total learning score, and side effects were evaluated before radiotherapy and 1, 3, 6, and 12 months after radiotherapy. This study analyzed the overall survival rate, progression-free survival rate, and changes in HVLT-R immediate recall scores. Results Forty patients were enrolled between Jan 2016 and Jan 2020. The median follow-up time was 14.2 months. The median survival, progression-free survival, and intracranial progression-free survival of all patients were 14.8 months, 6.7 months and 14.8 months, respectively. Multivariate analysis indicated that male sex and newly diagnosed stage IV disease were associated with poor overall survival and progression-free survival, respectively. HVLT-R scores at baseline and 1, 3, and 6 months after radiotherapy were 21.94 ± 2.99, 20.88 ± 3.12, 20.03 ± 3.14, and 19.78 ± 2.98, respectively. The HVLT-R scores at 6 months after radiotherapy decreased by approximately 9.8% compared with those at baseline. No grade 3 toxicities occurred in the entire cohort. Conclusions HA-WBRT-SIB is of efficiency and cognitive-conserving in treating Chinese lung cancer BM. Trial registration This study was retrospectively registered on ClinicalTrials.gov in 24th Feb, 2024. The ClinicalTrials.gov ID is NCT06289023.

ABSTRACT Background The prognosis of high‐risk neuroblastomas (NB) that are resistant to first‐line induction chemotherapy is relatively poor. This study explored the mechanism of resistance to first‐line chemotherapeutics mediated by TXNDC17 and its potential solutions in NB. Methods The genetic and clinical data of patients with NB were obtained from the Therapeutically Applicable Research to Generate Effective Treatments dataset. TXNDC17 and BECN1 expressions in NB cells were up‐ and downregulated by transfection with plasmids and shRNA, respectively. Autophagy‐related proteins were detected by western blot. Cell viability was determined using cell proliferation and toxicity experiments. Apoptotic cells were detected using flow cytometry. Results Overall, 1076 pediatric and adolescent patients with NB were enrolled in this study. The 10‐year overall survival (OS) rates and event‐free survival (EFS) rates for the patients with a mutation of BECN1 were 37.4 ± 9.1% and 34.5 ± 8.8%, respectively. For patients with a mutation of TXNDC17, the 10‐year OS and EFS were 41.4 ± 5.9% and 24.3 ± 5.1%, respectively, which were significantly lower than those in the unaltered group. The overexpression of BECN1 and TXNDC17 reduced NB sensitivity to cisplatin (DDP), etoposide (VP16), and cyclophosphamide (CTX). Autophagy mediated by BECN1 was regulated by TXNDC17, and this process was involved in the resistance to DDP, VP16, and CTX in NB. Suberoylanilide hydroxamic acid (SAHA) can enhance the sensitivity and apoptosis of NB cells to chemotherapeutics by inhibiting TXNDC17, ultimately decreasing autophagy‐mediated chemoresistance. Conclusions Acquired resistance to first‐line chemotherapeutics was associated with autophagy mediated by BECN1 and regulated by TXNDC17, which can be reversed by SAHA.

Abstract Autonomous robotic massage holds the potential to alleviate the workload of nurses and improve the quality of healthcare. However, the complexity of the task and the dynamic of the environment present significant challenges for robotic massage. This paper presents a vision-based robotic massage (VBRM) framework that facilitates autonomous robot massaging of the human body while ensuring safe operation in a dynamic environment. The VBRM framework allows the operator to define the massage trajectory by drawing a 2D curve on an RGB image. An interactive trajectory planning method is developed to calculate a 3D massage trajectory from the 2D trajectory. This method accounts for potential movements of the human body and updates the planned trajectory using rigid point cloud registration. Additionally, a hybrid motion/force controller is employed to regulate the motion of the robot’s end-effector, considering the possibility of excessive contact force. The proposed framework enables the operator to adjust the massage trajectory and speed according to their requirements. Real-world experiments are conducted to evaluate the efficacy of the proposed approach. The results demonstrate that the framework enables successful planning and execution of the massage task in a dynamic environment. Furthermore, the operator has the flexibility to set the massage trajectory, speed, and contact force arbitrarily, thereby enhancing human–machine interaction.

BackgroundTo assess the bioequivalence between Gan & Lee (GL) glargine U300 and Toujeo® regarding pharmacokinetics (PK), pharmacodynamics (PD), and safety in Chinese healthy male participants.MethodsA single-center, randomized, double-blind, single-dose, two-preparation, two-sequence, four-cycle repeated crossover design study was performed to compare GL glargine U300 and Toujeo® in 40 healthy participants. The primary PK endpoints were the area under the curve of glargine metabolites, M1 concentration from 0 to 24 hours (AUC0-24h), and the maximum glargine concentration within 24 hours post-dose (Cmax). The primary PD endpoints were the area under the glucose infusion rate (GIR) curve from 0 to 24 hours (AUCGIR.0-24h) and the maximum GIR within 24 hours post-dose (GIRmax).ResultsGL Glargine U300 demonstrated comparable PK parameters (AUC0–24h, Cmax, AUC0–12h, and AUC12–24h of M1) and PD responses [AUCGIR.0–24h, GIRmax, AUCGIR.0–12h, and AUCGIR.12–24h] to those of Toujeo®, as indicated by 90% confidence intervals ranging from 80% to 125%. No significant disparities in safety profiles were observed between the two treatment groups, and there were no reported instances of serious adverse events.ConclusionThe PK, PD, and safety of GL glargine U300 were bioequivalent to that of Toujeo®.Clinical trial registrationhttps://www.chinadrugtrials.org.cn/, identifier CTR20212419.

Hepatocellular carcinoma (HCC) is the major cause of cancer-associated mortality worldwide. Despite great advances have been made on the treatment of HCC, the survival rate of patients remains poor. Spindle apparatus coiled-coil protein 1 (SPDL1) is involved in the development of various cancers in humans. However, the role of SPDL1 in HCC remains unclear. In this study, we found high expression of SPDL1 in HCC tissues as compared to normal samples. In vitro, silencing of SPDL1 induced HCC cell apoptosis, and suppressed HCC cell propagation and migration. In vivo, knockdown of SPDL1 inhibited the tumor growth of HCC cells. These findings indicated the tumor-promoting role of SPDL1 in HCC. Mechanistically, we identified farnesyltransferase-beta (FNTB) as the downstream target protein of SPDL1 based on immunoprecipitation and mass spectrometry, which were confirmed by western blotting. Rescue assay determined that FNTB played a tumor promoting role in SPDL1-trigger HCC cell growth. Overexpression of FNTB recovered HCC cell viability and migration in SPDL1 knockdown cells. We also found that silencing of SPDL1 increased the sensitivity of Huh7 cells to sorafenib and lenvatinib, suggesting that SPDL1 is a new therapeutic target in HCC. Collectivity, the present study identified a new axis SPDL1/FNTB involved in the progression of HCC. Hence, SPDL1/FNTB is a potential target for the treatment of HCC.

Peak limiter-based techniques such as peak canceler (PC) have been investigated as simple solutions for reducing the peak-to-average power ratio (PAPR) in massive multi-input multi-output (mMIMO) orthogonal frequency division multiplexing (OFDM) systems. An important shortcoming of using peak limiter strategies is degradation of the transmitted signal quality, such as the bit error rate (BER), because of in-band distortion caused by peak limiting. To address this shortcoming, an in-band distortion compensation method has been proposed. With this method, a subset of transmit antennas at the base station is dedicated to mitigate in-band distortion caused by peak cancellation. However, the success of this approach depends on the spatial arrangement of the antennas and the precoder design. As described herein, we propose an improved in-band distortion compensation method for PC-based PAPR reduction in uniform planar array (UPA) mMIMO OFDM systems. Using the proposed method, the distortion compensation accuracy can be improved by properly determined placement of in-band distortion compensation antennas. We demonstrate that the proposed method using a minimum mean square error (MMSE) precoder achieves lower in-band distortion effectively and that it consequently provides better BER performance while maintaining comparable PAPR reduction capabilities to those of conventional methods.

To solve the problems of limited computing power resources, low accuracy of small target detection, high miss rate, and poor real-time detection of mobile vehicle platforms in the automatic driving environment, The present study introduced a one-stage target detection algorithm TTD-YOLO (Traffic Target Detection YOLO) that improved YOLOV5-S, which is enhanced in four aspects: Enhanced the network’s multi-scale feature extraction performance through the utilization of the improved M-ELAN architecture; added 3D attention mechanism SimAM to the network structure to enable the network to learn important feature information and enhance the efficiency of detecting accuracy; the parameter ratio of backbone and neck is adjusted to close to 1:1 by adjusting the number of output channels and stacking times of CSPLayer modules in the backbone and neck, while maintaining the model complexity, experiments show that improving the neck’s parameter ratio helps enhance the efficiency of detecting accuracy without changing the network structure; used EIoU loss instead of the bounding box loss function accelerates network convergence and improved detection accuracy. Under the condition of avoiding significantly changing the network structure, our TTD-YOLO outperforms the baseline model and other mainstream object detection algorithms such as Faster RCNN, SSD, and YOLOX-S on the autopilot dataset SODA10M with fewer parameters, higher detection accuracy, and faster inference speed. Compared to the baseline model, the model parameters decreased by 8.6%, average precision(mAP@.5:.95)increased by 2.5%, and the inference speed under the same experimental platform increased by 4.8%.

To address the shortcomings of the classical RRT (Rapidly exploring Range Tree) path planning algorithm, such as long planning time and path curvature in some narrow and complex environments, an improved APG-RRT (Adaptive Path Guide RRT) algorithm is proposed. First, a guiding path is introduced in the sampling stage, and a node on the preset guiding path is selected first to expand the node tree so as to guide the algorithm to plan the exploration process. Secondly, the selection weight of the loading guidance path is dynamically adjusted according to the probability of collision between obstacles during the exploration process, and a safe and feasible path point is generated in the path expansion stage by combining the expansion information of the obstacles. Finally, in the path post-processing stage, combined with the vehicle kinematic constraints, the triangular inequality method is used to remove redundant path points, making the path more smooth, so as to fulfill the specific operational needs of the vehicle. The results of the simulation experiment demonstrate that the suggested method exhibits superior planning efficiency compared to the previous algorithm, resulting in a higher quality final path. At the same time, the verification of the algorithm’s feasibility and effectiveness is conducted through real car testing.

Skin mast cells (MCs) mediate acute allergic reactions in the cutaneous environment and contribute to chronic dermatoses, including urticaria, and atopic or contact dermatitis. The cAMP response element binding protein (CREB), an evolutionarily well conserved transcription factor (TF) with over 4,000 binding sites in the genome, was recently found to form a feedforward loop with KIT, maintaining MC survival. The most selective MC function is degranulation with its acute release of prestored mediators. Herein, we asked whether CREB contributes to the expression and function of the degranulation-competent receptors FcεRI and MRGPRX2. Interference with CREB by pharmacological inhibition (CREBi, 666-15) or RNA interference only slightly affected the expression of these receptors, while KIT was strongly attenuated. Interestingly, MRGPRX2 surface expression moderately increased following CREB-knockdown, whereas MRGPRX2-dependent exocytosis simultaneously decreased. FcεRI expression and function were regulated consistently, although the effect was stronger at the functional level. Preformed MC mediators (tryptase, histamine, β-hexosaminidase) remained comparable following CREB attenuation, suggesting that granule synthesis did not rely on CREB function. Collectively, in contrast to KIT, FcεRI and MRGPRX2 moderately depend on unperturbed CREB function. Nevertheless, CREB is required to maintain MC releasability irrespective of stimulus, insinuating that CREB may operate by safeguarding the degranulation machinery. To our knowledge, CREB is the first factor identified to regulate MRGPRX2 expression and function in opposite direction. Overall, the ancient TF is an indispensable component of skin MCs, orchestrating not only survival and proliferation but also their secretory competence.

The morphology and function of the cerebellum are associated with various developmental disorders and healthy aging. Changes in cerebellar morphology during the aging process have been extensively investigated, with most studies focusing on changes in cerebellar regional volume. The volumetric method has been used to quantitatively demonstrate the decrease in the cerebellar volume with age, but it has certain limitations in visually presenting the morphological changes of cerebellar atrophy from a three-dimensional perspective. Thus, we comprehensively described cerebellar morphological changes during aging through volume measurements of subregions and shape analysis. This study included 553 healthy participants aged 20–80 years. A novel cerebellar localized segmentation algorithm based on convolutional neural networks was utilized to analyze the volume of subregions, followed by shape analysis for localized atrophy assessment based on the cerebellar thickness. The results indicated that out of the 28 subregions in the absolute volume of the cerebellum, 15 exhibited significant aging trends, and 16 exhibited significant sex differences. Regarding the analysis of relative volume, only 11 out of the 28 subregions of the cerebellum exhibited significant aging trends, and 4 exhibited significant sex differences. The results of the shape analysis revealed region-specific atrophy of the cerebellum with increasing age. Regions displaying more significant atrophy were predominantly located in the vermis, the lateral portions of bilateral cerebellar hemispheres, lobules I-III, and the medial portions of the posterior lobe. This atrophy differed between sexes. Men exhibited slightly more severe atrophy than women in most of the cerebellar regions. Our study provides a comprehensive perspective for observing cerebellar atrophy during the aging process.

The dual-channel graph convolutional neural networks based on hybrid features jointly model the different features of networks, so that the features can learn each other and improve the performance of various subsequent machine learning tasks. However, current dual-channel graph convolutional neural networks are limited by the number of convolution layers, which hinders the performance improvement of the models. Graph convolutional neural networks superimpose multi-layer graph convolution operations, which would occur in smoothing phenomena, resulting in performance decreasing as the increasing number of graph convolutional layers. Inspired by the success of residual connections on convolutional neural networks, this paper applies residual connections to dual-channel graph convolutional neural networks, and increases the depth of dual-channel graph convolutional neural networks. Thus, a dual-channel deep graph convolutional neural network (D2GCN) is proposed, which can effectively avoid over-smoothing and improve model performance. D2GCN is verified on CiteSeer, DBLP, and SDBLP datasets, the results show that D2GCN performs better than the comparison algorithms used in node classification tasks.

A facile and cost-effective approach for hierarchically porous ceramics has been proposed firstly, using coal fly ash as the main powder while secondary aluminum dross (SAD) as curing and foaming agents. Benefited from the hydrolysis of AlN and Al in SAD, gas and lamellar aluminum hydroxide sol attached to the surface of unreacted particles were produced, meanwhile pH value and viscosity increased, realizing foaming and coagulation casting simultaneously to fabricate porous green body. The increase of SAD amount could contribute to more intensive formation of flaky aluminum hydroxide sol, enhancing mechanical strength of green body, which has high compressive strength of 1.03 MPa at a bulk density of 0.68 g/cm3. Porous mullite-based ceramics could be sintered at a relatively low temperature of 1200–1250 °C owing to alkali metal oxide and amorphous SiO2 in the solid wastes, which also help to form micropores on the pore wall due to partially sintering. Porous mullite-based ceramics possess hierarchical pores, bulk density of 1.00 g/cm3, open porosity of 66.15%, specific surface area of 2.24 m2/g and compressive strength of 9.14 MPa. Their removal rate of malachite green solution reaches 99.1% at a concentration of 100 mg/L and an adsorbent dosage of 100 g/L.

Highlights Heterostructure engineering is proposed to construct CoTe2/ZnTe heterostructures with built-in electric field. Conductive and elastic Ti3C2T x MXene is introduced to improve the conductivity and alleviate the volume change of CoTe2/ZnTe upon cycling. The resulting CoTe2/ZnTe/Ti3C2T x (CZT) demonstrates outstanding rate capability (137.0 mAh g−1 at 10 A g−1) and cycling stability (175.3 mAh g−1 after 4000 cycles at 3.0 A g−1). Moreover, the CZT-based full cells demonstrate excellent energy density (220.2 Wh kg−1) and power density (837.2 W kg−1).

This paper investigates the impact of cognitive load on the formation and maintenance of cooperation within a public goods game experiment featuring a punishment option. By integrating the experimental designs of prior studies and manipulating cognitive load through the memorization of numbers with varying digits, we reveal that high cognitive load accelerates the breakdown of cooperation, irrespective of the presence of a punishment system. Furthermore, under high cognitive load, participants are more likely to engage in antisocial punishment, while the punishment of free riders remains unaffected. These findings suggest that increased cognitive load depletes the cognitive resources needed for deliberative decision-making, leading to a higher propensity for antisocial punishment. Our study contributes to the literature by demonstrating the significant influence of cognitive load on cooperative behavior and providing new insights into the causes of antisocial punishment.

Powder metallurgy is widely used to fabricate high-nitrogen, nickel-free austenitic stainless steel. However, after sintering and nitriding, additional solution treatment is typically required to achieve uniform nitrogen distribution and a homogeneous austenite phase. This work proposes a novel method to eliminate the need for lengthy and high-temperature solution treatment by switching the nitrogen atmosphere to argon during the cooling process. The effects of different N2-Ar atmosphere-switching temperatures (750–1320 °C) on the phase composition, element distribution, microstructure, mechanical properties, and corrosion resistance of the studied steels were systematically investigated. Results show that cooling in the N2 atmosphere initially transforms the matrix to a fully austenitic structure enriched with nitrogen. Excessive nitrogen infiltration leads to Cr2N precipitation, inducing partial austenite decomposition and forming a multiphase structure comprising austenite, α-Fe, and Cr2N. Strategic switching from N2 to Ar reverses this reaction, yielding a high-nitrogen, chemically uniform austenitic structure. Specifically, switching at 1150 °C, the steel exhibits excellent mechanical properties and corrosion resistance, with a yield strength of 749 MPa, an ultimate tensile strength of 1030 MPa, an elongation of 38.7%, and a corrosion current of 0.06 mA/cm2, outperforming the steels cooled solely in N2 and subsequently solution-treated. This novel method offers advantages in cost reduction, energy saving, and operational effectiveness, highlighting its potential for broad industrial application.

Cryptococcus neoformans poses a threat to human health, but anticryptococcal therapy is hampered by the emergence of drug resistance, whose underlying mechanisms remain poorly understood. Herein, we discovered that Isw1, an imitation switch chromatin remodeling ATPase, functions as a master modulator of genes responsible for in vivo and in vitro multidrug resistance in C. neoformans. Cells with the disrupted ISW1 gene exhibited profound resistance to multiple antifungal drugs. Mass spectrometry analysis revealed that Isw1 is both acetylated and ubiquitinated, suggesting that an interplay between these two modification events exists to govern Isw1 function. Mutagenesis studies of acetylation and ubiquitination sites revealed that the acetylation status of Isw1K97 coordinates with its ubiquitination processes at Isw1K113 and Isw1K441 through modulating the interaction between Isw1 and Cdc4, an E3 ligase. Additionally, clinical isolates of C. neoformans overexpressing the degradation-resistant ISW1K97Q allele showed impaired drug-resistant phenotypes. Collectively, our studies revealed a sophisticated acetylation–Isw1–ubiquitination regulation axis that controls multidrug resistance in C. neoformans.

Abstract Background Mesonephric carcinoma (MC) is a very rare tumor with less than 70 cases had been reported. The rarity of MC has restricted its research, resulting in the lack of published guidelines. Objective To summarize the characteristics and construct an external‐validated nomogram to predict the survival of MC patients. Method Sixty‐four qualified patients derived from the Surveillance, Epidemiology, and End Results Plus database, and one patient from the Guangzhou Red Cross Hospital were enrolled. The entire cohort was randomly divided into a development (70%) and a validation cohort (30%). The Kaplan–Meier method and univariate and multivariate Cox regression analyses were applied. Two nomograms were established to predict the 3‐to‐8‐year survival probability of MC patients, which were evaluated by C‐index, ROC curves, DCA curves, and calibration plots. Results The average survival time of MC patients was 84.22 ± 50.66 months. No significant difference was shown among different groups of race, primary site, tumor differentiated grade, and FIGO stages, while different SEER stages did distinguish patients' survival time, which indicated that the SEER stage standards might be a better staging system in the MC patients than FIGO stage (p = .0835). Additional survival analyses showed that MC patients benefited from shorter waiting times to begin treatment, accepting surgery, regional lymph node examination, radiotherapy, and chemotherapy. Two nomograms were established, both of which got satisfied scores in C‐index, ROC curves, DCA curves, and calibration plots. Conclusion Sufficient regional lymph nodes examined, and applying radiotherapy in high‐risk patients are recommended in MC patients. Nomograms established in the present study had good predicting and discriminating capabilities, which would be helpful in patients' individual risk estimation, management, counseling, and follow‐up.

Abstract Background In bladder cancer, recurrent ADGRG6 enhancer hotspot mutations (chr. 6: 142,706,206 G>A, chr. 6:142,706,209 C>T) were reported at a high mutation rate of approximately 50%. Thus, ADGRG6 enhancer mutation status might be a candidate for diagnostic biomarker. Methods To improve test efficacy, an amplification refractory mutation system combined with quantitative real‐time PCR (ARMS‐qPCR) assay was developed to detect the ADGRG6 mutations in a patient as a clinical diagnostic test. To validate the performance of the ARMS‐qPCR assay, artificial plasmids, cell DNA reference standard were used as templates, respectively. To test the clinical diagnostic ability, we detected the cell free DNA (cfDNA) and sediment DNA (sDNA) of 30 bladder cancer patients' urine by ARMS‐qPCR comparing with Sanger sequencing, followed by the droplet digital PCR to confirm the results. We also tested the urine of 100 healthy individuals and 90 patients whose diagnoses urinary tract infections or urinary stones but not bladder cancer. Results Sensitivity of 100% and specificity of 96.7% were achieved when the mutation rate of the artificial plasmid was 1%, and sensitivity of 96.7% and specificity of 100% were achieved when the mutation frequency of the reference standard was 0.5%. Sanger sequencing and ARMS‐qPCR both detected 30 cases of bladder cancer with 93.3% agreement. For the remaining unmatched sites, ARMS‐qPCR results were consistent with droplet digital PCR. Among 100 healthy individuals, three of them carried hotspot mutations by way of ARMS‐qPCR. Of 90 patients with urinary tract infections or urinary stones, no mutations were found by ARMS‐qPCR. Based on clinical detection, the ARMS‐qPCR assay's sensitivity is 83.3%, specificity is 98.4%. Conclusion We here present a novel urine test for ADGRG6 hotspot mutations with high accuracy and sensitivity, which may potentially serve as a rapid and non‐invasive tool for bladder cancer early screening and follow‐up relapse monitoring.

Abstract BackgroundDespite pediatric populations representing a smaller proportion of COVID-19 cases and having a less severe prognosis, those belonging to racial and ethnic minority groups are at an increased risk of developing more severe COVID-19–related outcomes. Vaccine coverage is crucial to pandemic mitigation efforts, yet since the start of the COVID-19 pandemic, vaccine hesitancy has increased and routine pediatric immunizations have decreased. Limited research exists on how vaccine hesitancy may contribute to low pediatric COVID-19 vaccine uptake among racial and ethnic minority populations. ObjectiveThis study aimed to characterize COVID-19 vaccine–related discussion and sentiment among Twitter users, particularly among racial and ethnic minority users. MethodsWe used the Twitter application programming interface to collect tweets and replies. Tweets were selected by filtering for keywords associated with COVID-19 vaccines and pediatric-related terms. From this corpus of tweets, we used the Biterm Topic Model to output topics and examined the top 200 retweeted tweets that were coded for pediatric COVID-19 vaccine relevance. Relevant tweets were analyzed using an inductive coding approach to characterize pediatric COVID-19 vaccine–related themes. Replies to relevant tweets were collected and coded. User metadata were assessed for self-reporting of race or ethnic group affiliation and verified account status. ResultsA total of 863,007 tweets were collected from October 2020 to October 2021. After outputting Biterm Topic Model topics and reviewing the 200 most retweeted tweets, 208,666 tweets and 3905 replies were identified as being pediatric COVID-19 vaccine related. The majority (150,262/208,666, 72.01%) of tweets expressed vaccine-related concerns. Among tweets discussing vaccine confidence, user replies expressing agreement were significantly outweighed by those expressing disagreement (1016/3106, 32.71% vs 2090/3106, 67.29%; P ConclusionsVaccine-related concerns can have negative consequences on vaccine uptake and participation in vaccine-related clinical trials. This can impact the uptake and development of safe and effective vaccines, especially among racial and ethnic minority populations.

Despite the distortion of speech signals caused by unavoidable noise in daily life, our ability to comprehend speech in noisy environments is relatively stable. However, the neural mechanisms underlying reliable speech-in-noise comprehension remain to be elucidated. The present study investigated the neural tracking of acoustic and semantic speech information during noisy naturalistic speech comprehension. Participants listened to narrative audio recordings mixed with spectrally matched stationary noise at three signal-to-ratio (SNR) levels (no noise, 3 dB, -3 dB), and 60-channel electroencephalography (EEG) signals were recorded. A temporal response function (TRF) method was employed to derive event-related-like responses to the continuous speech stream at both the acoustic and the semantic levels. Whereas the amplitude envelope of the naturalistic speech was taken as the acoustic feature, word entropy and word surprisal were extracted via the natural language processing method as two semantic features. Theta-band frontocentral TRF responses to the acoustic feature were observed at around 400 ms following speech fluctuation onset over all three SNR levels, and the response latencies were more delayed with increasing noise. Delta-band frontal TRF responses to the semantic feature of word entropy were observed at around 200 to 600 ms leading to speech fluctuation onset over all three SNR levels. The response latencies became more leading with increasing noise and decreasing speech comprehension and intelligibility. While the following responses to speech acoustics were consistent with previous studies, our study revealed the robustness of leading responses to speech semantics, which suggests a possible predictive mechanism at the semantic level for maintaining reliable speech comprehension in noisy environments.

Abstract Ocean vertical velocity (w) plays a key role in regulating the exchanges of mass, heat and nutrients between the surface and deep ocean. However, direct observation remains difficult due to its small magnitude and large spatiotemporal variability. Therefore, w fields are generally diagnosed using dynamic‐based methods. In this study, we developed a deep neural network (DNN) to reconstruct three‐dimensional fields of ocean vertical velocity based on sea surface height (SSH) fields. Compared to dynamic‐based methods, the DNN shows improved performance in the w reconstruction within upper 500 m in terms of higher correlation and less error. Remarkably, the DNN requires only a ∼45 × 45 km size SSH image as input to estimate w at the center. This suggests that the DNN has great potential for w reconstruction in the future combined with high‐resolution observations such as the Surface Water and Ocean Topography mission.

Motion planning between dynamic obstacles is an essential capability to achieve real-world navigation. In this study, we investigated the problem of avoiding dynamic obstacles in complex environments for a car-like mobile robot with an incompletely constrained Ackerman front wheel steering. To address the problems of weak dynamic obstacle avoidance and poor path smoothing in motion planning with the traditional Timed Elastic Band (TEB) algorithm, We proposed a hybrid motion planning algorithm (TEB-CA,Timed Elastic Band-Collision Avoidance) that combines an improved traditional TEB algorithm and Optimal Reciprocal Collision Avoidance (ORCA) model to improve the ability of the robot to predict dynamic obstacles in advance and avoid collisions safely. Moreover, We also add new constraints to the traditional TEB algorithm, including: jerk constraints, smoothness constraints, and curvature constraints. The algorithm is implemented in $C++$ and evaluated experimentally in the Gazebo and Rviz simulation environments of the Robot Operating System (ROS), as well as in actual experimental tests on our car-like autonomous mobile robot “Little Ant” which proves the effectiveness of the method, and that the motion planning scheme is more effective in avoiding dynamic obstacles than the traditional TEB and DWA algorithms.

During the production and assembly process of televisions, the efficiency of assembly is limited by manual assembly methods. Conventional image matching algorithms such as SIFT and ORB fail to meet the real-time accuracy requirements of intelligent assembly processes. To address this issue, a novel algorithm called Adaptive Threshold oFAST and rBRIEF-BRISK (AFK) is proposed. This algorithm utilizes the Hamming distance as a similarity measure and integrates AToFAST and rBRIEF-BRISK fusion feature descriptors. Through a comparison of 12 sets of image matching scenarios, it is demonstrated that the AFK algorithm achieves a matching speed 4.5 times faster than the SIFT algorithm, with an image matching accuracy of up to 90%. Additionally, this paper presents the GLMLBP-TOP (Global-Local and Michelson Contrast LBP-Three Orthogonal Planes) dynamic texture recognition method. Through a comparison of 21 sets experiments, it is shown that the comprehensive classification accuracy of the GLMLBP-TOP method is approximately 94.5%, improving the performance of VLBP (87.71%) and LBP-TOP (91.1%) by 6.79% and 3.4% respectively. Real-world application results demonstrate that this method meets the requirements of intelligent assembly processes and has been successfully applied to the LB intelligent assembly process of a certain company’s televisions.

Introduction In 2019, the state of Massachusetts signed into law the first statewide sales restrictions of flavored ENDS/tobacco products for both physical and online shops in response to a previous executive order to curb E-Cigarette, or Vaping Product, Use Associated Lung Injury (EVALI) cases that were surging throughout the nation. Methodology This study obtained licensure data from the Massachusetts Department of Revenue, to observe the changes in retail licensure comparing the pre ban (October 2018-August 2019) and post ban periods (October 2020- August 2021). A series of linear regression tests were conducted on both periods using census tract data to explore potential associations with sociodemographic covariates, including median age, median household income, and population proportion by gender, age, and race/ethnicity groups. Results Analysis of the Massachusetts post-ban period (October 2020-August 2021) found that new tobacco retail licenses issued decreased by 52.9% (n = 968) when compared to the pre-ban period (October 2018-August 2019) of 1831. A significant positive association was discovered between change in new retailer count and proportion male population (2.48 ± 1.05, P = .018) as well as proportion Hispanic population (1.19 ± .25, P < .001) at the census tract level. Conclusion/Discussion Our analysis indicates that, following the temporary MA flavor sales ban, the total number of licenses decreased, though decreases were more pronounced for new licenses when compared to continuing licenses. Higher increases in new tobacco retailer density were significantly associated with concentration of male and Hispanic populations.

Resources in primary schools can be classified into three types: campus, teaching, and community resources. Urban–rural differences in the resources of Chinese county schools, which are triggered by population migration and residents’ preference for high-quality schools, are a common phenomenon emerging in the context of rapid urbanization. Despite the negative effects of these resource differences on social sustainability and the increasing need to comprehensively analyze urban–rural differences in school resources, to date there has not been an effective analytical framework for resolving these issues. To address this research gap, this study develops a method using the entropy-based Technique for Order Preference by Similarity to Ideal Solution (TOPSIS), spatial analysis, and statistical analysis for assessing resource equity in primary schools by means of the relative proximities of resources. The resource differences between urban and rural primary schools are quantitatively investigated through taking Yuncheng County as a case study. The urban–rural differences in the three types of resources are discovered and presented according to geographical location. The research findings make contributions to understanding the unbalanced distribution of school resources, promoting equity in education, and improving the social sustainability of counties. Additionally, the analytical framework has the potential to be extended to analyzing urban–rural resource differences in secondary or high schools.

Dental pulp pericytes are reported to have the capacity to generate odontoblasts and express multiple cytokines and chemokines that regulate the local immune microenvironment, thus participating in the repair of dental pulp injury in vivo. However, it has not yet been reported whether the transplantation of exogenous pericytes can effectively treat pulpitis, and the underlying molecular mechanism remains unknown. In this study, using a lineage-tracing mouse model, we showed that most dental pulp pericytes are derived from cranial neural crest. Then, we demonstrated that the ablation of pericytes could induce a pulpitis-like phenotype in uninfected dental pulp in mice, and we showed that the significant loss of pericytes occurs during pupal inflammation, implying that the transplantation of pericytes may help to restore dental pulp homeostasis during pulpitis. Subsequently, we successfully generated pericytes with immunomodulatory activity from human pluripotent stem cells through the intermediate stage of the cranial neural crest with a high level of efficiency. Most strikingly, for the first time we showed that, compared with the untreated pulpitis group, the transplantation of hPSC-derived pericytes could substantially inhibit vascular permeability (the extravascular deposition of fibrinogen, ** p < 0.01), alleviate pulpal inflammation (TCR+ cell infiltration, * p < 0.05), and promote the regeneration of dentin (** p < 0.01) in the mouse model of pulpitis. In addition, we discovered that the knockdown of latent transforming growth factor beta binding protein 1 (LTBP1) remarkably suppressed the immunoregulation ability of pericytes in vitro and compromised their in vivo regenerative potential in pulpitis. These results indicate that the transplantation of pericytes could efficiently rescue the aberrant phenotype of pulpal inflammation, which may be partially due to LTBP1-mediated T cell suppression.

Skin mast cells (MCs) are critical effector cells in acute allergic reactions, and they contribute to chronic dermatoses like urticaria and atopic and contact dermatitis. KIT represents the cells‘ crucial receptor tyrosine kinase, which orchestrates proliferation, survival, and functional programs throughout the lifespan. cAMP response element binding protein (CREB), an evolutionarily well-conserved transcription factor (TF), regulates multiple cellular programs, but its function in MCs is poorly understood. We recently reported that CREB is an effector of the SCF (Stem Cell Factor)/KIT axis. Here, we ask whether CREB may also act upstream of KIT to orchestrate its functioning. Primary human MCs were isolated from skin and cultured in SCF+IL-4 (Interleukin-4). Pharmacological inhibition (666-15) and RNA interference served to manipulate CREB function. We studied KIT expression using flow cytometry and RT-qPCR, KIT-mediated signaling using immunoblotting, and cell survival using scatterplot and caspase-3 activity. The proliferation and cycle phases were quantified following BrdU incorporation. Transient CREB perturbation resulted in reduced KIT expression. Conversely, microphthalmia transcription factor (MITF) was unnecessary for KIT maintenance. KIT attenuation secondary to CREB was associated with heavily impaired KIT functional outputs, like anti-apoptosis and cell cycle progression. Likewise, KIT-elicited phosphorylation of ERK1/2 (Extracellular Signal-Regulated Kinase 1/2), AKT, and STAT5 (Signal Transducer and Activator of Transcription) was substantially diminished upon CREB inhibition. Surprisingly, the longer-term interference of CREB led to complete cell elimination, in a way surpassing KIT inhibition. Collectively, we reveal CREB as non-redundant in MCs, with its absence being incompatible with skin MCs’ existence. Since SCF/KIT regulates CREB activity and, vice versa, CREB is required for KIT function, a positive feedforward loop between these elements dictates skin MCs’ fate.

In this study, the nanostructured Al/Ni energetic composites were processed using the high-energy ball milling method. The milling conditions, i.e. the ball to powder ratio (BPR), ball sizes, and milling time, were varied to investigate their effect on the microstructures and reaction properties of the Al/Ni NECs. Results indicated that large BPR, appropriate size assortment of milling balls, and long milling time promoted the formation of nano lamellar structure and improved the reaction performance. When the BPR was 10 and the milling time was 100min, the Al/Ni NECs had a nano lamellar structure and a low ignition temperature of 619 K. The activation energy was calculated to be 54.49 kJ/mol using the Kissinger method, and 63.87 kJ/mol using the Ozawa method, respectively.

BackgroundMale breast cancer (MBC) is rare, which has restricted prospective research among MBC patients. With effective treatments, the prognosis of MBC patients has improved and developing a second primary malignancy (SPM) has become a life-threatening event for MBC survivors. However, few studies have focused on the prognosis of MBC patients and looked into the SPM issue in MBC survivors.MethodWe reviewed MBC patients diagnosed between 1990 and 2016 from the latest Surveillance, Epidemiology, and End Results (SEER) Plus database. Competing risk models and nomograms were conducted for predicting the risk of cancer-specific death and SPM occurrence. C-indexes, calibration curves, ROC curves, and decision curve analysis (DCA) curves were applied for validation.ResultA total of 1,843 MBC patients with complete information were finally enrolled and 60 (3.26%) had developed an SPM. Prostate cancer (40%) was the most common SPM. The median OS of all the enrolled patients was 102.41 months, while the median latency from the initial MBC diagnosis to the subsequent diagnosis of SPM was 67.2 months. The patients who suffered from an SPM shared a longer OS than those patients with only one MBC (p = 0.027). The patients were randomly divided into the development cohort and the validation cohort (at a ratio of 7:3). The Fine and Gray competing risk model was used to identify the risk factors. Two nomograms were constructed and validated to predict the 5-year, 8-year, and 10-year survival probability of MBC patients, both of which had good performance in the C-index, ROC curves, calibration plots, and DCA curves, showing the ideal discrimination capability and predictive value clinically. Furthermore, we, for the first time, constructed a nomogram based on the competing risk model to predict the 5-year, 8-year, and 10-year probability of developing an SPM in MBC survivors, which also showed good discrimination, calibration, and clinical effectiveness.ConclusionWe, for the first time, included treatment information and clinical parameters to construct a nomogram to predict not only the survival probability of MBC patients but also the probability of developing an SPM in MBC survivors, which were helpful in individual risk estimation, patient follow-up, and counseling in MBC patients.

BackgroundNanosized bacterial outer membrane vesicles (OMVs) secreted by Gram-negative bacteria have emerged as a novel antitumor nanomedicine reagent due to their immunostimulatory properties. The encapsulated bacterial composition in OMVs can be edited via manipulating bioengineering technology on paternal bacteria, allowing us to design an ingenious antitumor platform by loading the Polybia–mastoparan I (MPI) fusion peptide into OMVs.MethodsOMVs containing the MPI fusion peptide were obtained from bioengineered Escherichia coli transformed with recombinant plasmid. The antitumor efficacy of bioengineered OMVs in vitro was verified by performing cell viability and wound-healing and apoptosis assays using MB49 and UMUC3 cells, respectively. Subcutaneous MB49 tumor-bearing mice were involved to investigate the tumor inhibition ability of bioengineered OMVs. Moreover, the activated immune response in tumor and the biosafety were also evaluated in detail.ResultsThe resulting OMVs had the successful encapsulation of MPI fusion peptides and were subjected to physical characterization for morphology, size, and zeta potential. Cell viabilities of bladder cancer cells including MB49 and UMUC3 rather than a non-carcinomatous cell line (bEnd.3) were decreased when incubated with bioengineered OMVs. In addition, bioengineered OMVs restrained migration and induced apoptosis of bladder cancer cells. With intratumor injection of bioengineered OMVs, growths of subcutaneous MB49 tumors were significantly restricted. The inherent immunostimulation of OMVs was demonstrated to trigger maturation of dendritic cells (DCs), recruitment of macrophages, and infiltration of cytotoxic T lymphocytes (CTLs), resulting in the increased secretion of pro-inflammatory cytokines (IL-6, TNF-α, and IFN-γ). Meanwhile, several lines of evidence also indicated that bioengineered OMVs had satisfactory biosafety.ConclusionBioengineered OMVs fabricated in the present study were characterized by strong bladder cancer suppression and great biocompatibility, providing a new avenue for clinical bladder cancer therapy.

IntroductionReporting speech is a basic form of human language, and reporting practices play a key role in news report. As one of the important rhetorical devices to introduce the reported speech, reporting verbs can help the readers understand the source of the reported speech and the attitude of the journalist or the media toward the reported information.MethodThis study examines the features of reporting practice in Chinese and American news reports on public health emergency by investigating the use of reporting verbs from the perspectives of critical discourse analysis. Two English news corpora of COVID-19 pandemic are built, namely, the China Daily News Corpus and the New York Times News Corpus, with 50 news texts in each corpus. The corpus analysis tool AntConc 3.3.5 is used to conduct concordance analysis.Results and discussionIt is found that Chinese and American news reports tend to use roughly the same high-frequency reporting verbs in reporting the COVID-19 pandemic. Chinese and American news corpora show difference in the distribution feature of high-frequency reporting verbs in terms of semantic category. Both Chinese and American news reports use speech reporting verbs most frequently, indicating an objective attitude toward the reported event, and use speech reporting verbs and speech act reporting verbs to introduce the reported speech with comparatively higher degree of certainty. American news reports frequently use mental reporting verbs to show the attitude of uncertainty toward the reported speech, and Chinese news reports probably need to raise the awareness of using mental reporting verbs to express the opinions and attitude of the common people or the authority. The findings of this study can provide insights into the research on reporting strategies of news reports on emergencies in China for foreign audience.

Introduction Exposure to pro-tobacco and electronic nicotine delivery system (ENDS) social media content can lead to overconsumption, increasing the likelihood of nicotine poisoning. This study aims to examine trends and characteristics of nicotine sickness content on Twitter between 2018–2020. Methods Tweets were collected retrospectively from the Twitter Academic Research Application Programming Interface (API) stream filtered for keywords: ‘nic sick’, ‘nicsick’, ‘vape sick’, ‘vapesick’ between 2018–2020. Collected tweets were manually annotated to identify suspected user-generated reports of nicotine sickness and related themes using an inductive coding approach. The Augmented Dickey-Fuller (ADF) test was used to assess stationarity in the monthly variation of the volume of tweets between 2018–2020. Results A total of 5651 tweets contained nicotine sickness-related keywords and 18.29% (n=1034) tweets reported one or more suspected nicotine sickness symptoms of varied severity. These tweets were also grouped into five related categories including firsthand and secondhand reports of symptoms, intentional overconsumption of nicotine products, users expressing intention to quit after ‘nic sick’ symptoms, mention of nicotine product type/brand name that they consumed while ‘nic sick’, and users discussing symptoms associated with nicotine withdrawal following cessation attempts. The volume of tweets reporting suspected nicotine sickness appeared to increase throughout the study period, except between February and April 2020. Stationarity in the volume of ‘nicsick’ tweets between 2018–2020 was not statistically significant (ADF= -0.32, p=0.98) indicating a change in the volume of tweets. Conclusions Results point to the need for alternative forms of adverse event surveillance and reporting, to appropriately capture the growing health burden of vaping. Infoveillance approaches on social media platforms can help to assess the volume and characteristics of user-generated content discussing suspected nicotine poisoning, which may not be reported to poison control centers. Increasing volume of user-reported nicotine sickness and intentional overconsumption of nicotine in twitter posts represent a concerning trend associated with ENDS-related adverse events and poisoning.

Coral’s susceptibility to bleaching is determined by the strength of the intricate mutual relationships among coral symbionts. However, there is limited knowledge about how the symbiotic members of the scleractinian coral Echinopora gemmacea respond to changes in their surrounding environmental conditions. In this study, we conducted a survey of seawater characteristics in the south and north zones of Wuzhizhou (WZZ) Island, measured symbiotic microalgal density and chlorophyll-a content in the corals, and performed metabarcoding of the Symbiodiniaceae and bacteria communities within coral tissue. Our findings demonstrated that the seawater in the north zone of WZZ Island had higher levels of turbidity, temperature, salinity, and dissolved oxygen content compared to the south zone. This indicated that the corals in the two zones were subjected to distinctive environmental conditions. Analysis of the Symbiodiniaceae composition revealed that Cladocopium sp. C1 and Cladocopium sp. C17 were the dominant species in the southern E. gemmacea, whereas Durusdinium sp. D1a and Cladocopium sp. C17 prevailed in the northern E. gemmacea. Consequently, symbiotic microalgal density and chlorophyll-a content were diminished in the northern E. gemmacea. Furthermore, correlation network analysis revealed the presence of intricate bacterial interactions that potentially mediate coral’s adaptation to environmental stress. This study provides insights into the differences in symbiotic members, including Symbiodiniaceae and bacteria, within E. gemmacea, and contributes to fundamental knowledge for coral conservation efforts.

Skin mast cells (MCs) express high levels of MRGPRX2, FcεRI, and ST2, and vigorously respond to their ligands when triggered individually. IL-33/ST2 also potently synergizes with other receptors, but the molecular underpinnings are poorly understood. Human skin-derived MCs were stimulated via different receptors individually or jointly in the presence/absence of selective inhibitors. TNF was quantified by ELISA. Signaling cascades were studied by immunoblot. TNF was stimulated by FcεRI ≈ ST2 > MRGPRX2. Surprisingly, neither FcεRI nor MRGPRX2 stimulation elicited NF-κB activation (IκB degradation, p65 phosphorylation) in stark contrast to IL-33. Accordingly, TNF production did not depend on NF-κB in FcεRI- or MRGPRX2-stimulated MCs, but did well so downstream of ST2. Conversely, ERK1/2 and PI3K were the crucial modules upon FcεRI/MRGPRX2 stimulation, while p38 was key to the IL-33-elicited route. The different signaling prerequisites were mirrored by their activation patterns with potent pERK/pAKT after FcεRI/MRGPRX2, but preferential induction of pp38/NF-κB downstream of ST2. FcεRI/MRGPRX2 strongly synergized with IL-33, and some synergy was still observed upon inhibition of each module (ERK1/2, JNK, p38, PI3K, NF-κB). IL-33’s contribution to synergism was owed to p38 > JNK > NF-κB, while the partner receptor contributed through ERK > PI3K ≈ JNK. Concurrent IL-33 led to slightly prolonged pERK (downstream of MRGPRX2) or pAKT (activated by FcεRI), while the IL-33-elicited modules (pp38/NF-κB) remained unaffected by co-stimulation of FcεRI/MRGPRX2. Collectively, the strong synergistic activity of IL-33 primarily results from the complementation of highly distinct modules following co-activation of the partner receptor rather than by altered signal strength of the same modules.

The multifunctional antibacterial peptide lactoferricin-lactoferrampin (LFCA) is derived from bovine lactoferrin. Optimization of the fermentation process should be studied since different microorganisms have their own favorable conditions and processes for growth and the production of metabolites. In this study, the culture conditions of a recombinant strain, pPG-LFCA-E/LR-CO21 (LR-LFCA), expressing LFCA was optimized, utilizing the high-density fermentation process to augment the biomass of LimosiLactobacillus reuteri and the expression of LFCA. Furthermore, an assessment of the protective effect of LR-LFCA on intestinal inflammation induced by lipopolysaccharide (LPS) was conducted to evaluate the impact of LR-LFCA on the disease resistance of piglets. The findings of this study indicate that LR-LFCA fermentation conditions optimally include 2% inoculation volume, 36.5 °C fermentation temperature, 9% dissolved oxygen concentration, 200 revolutions/minute stirring speed, pH 6, 10 mL/h glucose flow, and 50% glucose concentration. The inclusion of fermented LR-LFCA in the diet resulted in an elevation of immunoglobulin levels, significant upregulation of tight junction proteins ZO-1 and occludin, reinforcement of the intestinal barrier function, and significant amelioration of the aberrant alterations in blood physiological parameters induced by LPS. These results offer a theoretical framework for the implementation of this micro-ecological preparation in the field of piglet production to enhance intestinal well-being.

The ATP-binding cassette subfamily G member 2 (ABCG2) serves crucial roles in secreting riboflavin and biotin vitamins into the milk of cattle, mice, and humans, as well as in the transportation of xenotoxic and cytostatic drugs across the plasma membrane. However, the specific role of the ABCG2 gene in water buffaloes (Bubalus bubalis), especially its effect on milk fat synthesis in buffalo mammary epithelial cells (BuMECs), remains inadequately understood. In this study, the full-length CDS of the buffalo ABCG2 gene was isolated and identified from the mammary gland in buffaloes. A bioinformatics analysis showed a high degree of similarity in the transcriptional region, motifs, and conservative domains of the buffalo ABCG2 with those observed in other Bovidae species. The functional role of buffalo ABCG2 was associated with the transportation of solutes across lipid bilayers within cell membranes. Among the 11 buffalo tissues detected, the expression levels of ABCG2 were the highest in the liver and brain, followed by the mammary gland, adipose tissue, heart, and kidney. Notably, its expression in the mammary gland was significantly higher during peak lactation than during non-lactation. The ABCG2 gene was identified with five SNPs in river buffaloes, while it was monomorphic in swamp buffaloes. Functional experiments revealed that ABCG2 increased the triglyceride (TAG) content by affecting the expression of liposynthesis-related genes in BuMECs. The results of this study underscore the pivotal role of the ABCG2 gene in influencing the milk fat synthesis in BuMECs.

Background/Aims To evaluate the effect and possible mechanism of growth hormone releasing hormone (GHRH) on chondrocytes of osteoarthritis (OA). Methods Articular chondrocytes were cultured and the expression of GHRH receptor in chondrocytes was detected. Then recombinant adenovirus GHRH (Ad-GHRH) was transfected to one group of chondrocytes. The expression of collagen type II, matrix metalloproteinase 13 (MMP-13) and signal transducer and activator of transcription 3 (STAT3) in each experimental group was determined by Western blot. Results The GHRH receptor was expressed in chondrocytes, and this provided a basis for further study of the role of GHRH in chondrocytes. Cell proliferation of the Ad-GHRH group was significantly higher than that of the OA group by CCK-8 assay. Compared with the OA-group, the protein expression of MMP‑13 was decreased in the Ad-GHRH group. Compared with the OA-group, the protein expression of collagen type II, phosphorylated STAT3 (P-STAT3) were increased in the Ad-GHRH group. Conclusions Our results show that the GHRH receptor is expressed in chondrocytes. GHRH can promote the proliferation of chondrocytes and the synthesis of type II collagen, and increase the extracellular matrix, which is achieved by phosphorylated STAT3 protein.

BackgroundThere were an estimated 100,306 drug overdose deaths between April 2020 and April 2021, a three-quarter increase from the prior 12-month period. There is an approximate 6-month reporting lag for provisional counts of drug overdose deaths from the National Vital Statistics System, and the highest level of geospatial resolution is at the state level. By contrast, public social media data are available close to real-time and are often accessible with precise coordinates. ObjectiveThe purpose of this study is to assess whether county-level overdose mortality burden could be estimated using opioid-related Twitter data. MethodsInternational Classification of Diseases (ICD) codes for poisoning or exposure to overdose at the county level were obtained from CDC WONDER. Demographics were collected from the American Community Survey. The Twitter Application Programming Interface was used to obtain tweets that contained any of the 36 terms with drug names. An unsupervised classification approach was used for clustering tweets. Population-normalized variables and polynomial population-normalized variables were produced. Furthermore, z scores of the Getis Ord Gi clustering statistic were produced, and both these scores and their polynomial counterparts were explored in regression modeling of county-level overdose mortality burden. A series of linear regression models were used for predictive modeling to explore the interpretability of the analytical output. ResultsModeling overdose mortality with normalized demographic variables alone explained only 7.4% of the variability in county-level overdose mortality, whereas this was approximately doubled by the use of specific demographic and Twitter data covariates based on a backward selection approach. The highest adjusted R2 and lowest AIC (Akaike Info Criterion) were obtained for the model with normalized demographic variables, normalized z scores from geospatial analyses, and normalized topic counts (adjusted R2=0.133, AIC=8546.8). The z scores of the Getis Ord Gi statistic appeared to have improved utility over population-normalization alone. In this model, median age, female population, and tweets about web-based drug sales were positively associated with opioid mortality. Asian race and Hispanic ethnicity were significantly negatively associated with county-level burdens of overdose mortality. ConclusionsSocial media data, when transformed using certain statistical approaches, may add utility to the goal of producing closer to real-time county-level estimates of overdose mortality. Prediction of opioid-related outcomes can be advanced to inform prevention and treatment decisions. This interdisciplinary approach can facilitate evidence-based funding decisions for various substance use disorder prevention and treatment programs.

Abstract Background Enterovirus 71 (EV71) usually infects infants causing hand-foot-mouth disease (HFMD), even fatal neurological disease like aseptic meningitis. Effective drug for preventing and treating EV71 infection is unavailable currently. EV71 3C mediated the cleavage of many proteins and played an important role in viral inhibiting host innate immunity. Promyelocytic leukemia (PML) protein, the primary organizer of PML nuclear bodies (PML-NBs), can be induced by interferon and is involved in antiviral activity. PML inhibits EV71 replication, and EV71 infection reduces PML expression, but the molecular mechanism is unclear. Methods The cleavage of PMLIII and IV was confirmed by co-transfection of EV71 3C protease and PML. The detailed cleavage sites were evaluated further by constructing the Q to A mutant of PML. PML knockout cells were infected with EV71 to identify the effect of cleavage on EV71 replication. Immunofluorescence analysis to examine the interference of EV71 3C on the formation of PML-NBs. Results EV71 3C directly cleaved PMLIII and IV. Furthermore, 3C cleaved PMLIV at the sites of Q430–A431 and Q444–S445 through its protease activity. Overexpression of PMLIV Q430A/Q444A variant exhibited stronger antiviral potential than the wild type. PMLIV Q430A/Q444A formed normal nuclear bodies that were not affected by 3C, suggesting that 3C may impair PML-NBs production via PMLIV cleavage and counter its antiviral activities. PML, especially PMLIV, which sequesters viral proteins in PML-NBs and inhibits viral production, is a novel target of EV71 3C cleavage. Conclusions EV71 3C cleaves PMLIV at Q430–A431 and Q444–S445. Cleavage reduces the antiviral function of PML and decomposes the formation of PML-NBs, which is conducive to virus replication.

Introductionbluetongue virus (BTV) infection triggers dramatic and complex changes in the host's transcriptional profile to favor its own survival and reproduction. However, there is no whole-transcriptome study of susceptible animal cells with BTV infection, which impedes the in-depth and systematical understanding of the comprehensive characterization of BTV-host interactome, as well as BTV infection and pathogenic mechanisms.Methodsto systematically understand these changes, we performed whole-transcriptome sequencing in BTV serotype 1 (BTV-1)-infected and mock-infected sheep embryonic testicular cells, and subsequently conducted bioinformatics differential analyses.Resultsthere were 1504 differentially expressed mRNAs, 78 differentially expressed microRNAs, 872 differentially expressed long non-coding RNAs, and 59 differentially expressed circular RNAs identified in total. Annotation from the Gene Ontology, enrichment from the Kyoto Encyclopedia of Genes and Genomes, and construction of competing endogenous RNA networks revealed differentially expressed RNAs primarily related to virus-sensing and signaling transduction pathways, antiviral and immune responses, inflammation, and development and metabolism related pathways. Furthermore, a protein-protein interaction network analysis found that BTV may contribute to abnormal spermatogenesis by reducing steroid biosynthesis. Finally, real-time quantitative PCR and western blotting results showed that the expression trends of differentially expressed RNAs were consistent with the whole-transcriptome sequencing data.Discussionthis study provides more insights of comprehensive characterization of BTV-host interactome, and BTV infection and pathogenic mechanisms.

The loss of tomatoes caused by Botrytis cinerea (B. cinerea) is one of the crucial issues restricting the tomato yield. This study screened the elicitor protein phosphopentomutase from Bacillus velezensis LJ02 (BvEP) which improves the tomato resistance to B. cinerea. Phosphatemutase was reported to play a crucial role in the nucleoside synthesis of various microorganisms. However, there is no report on improving plant resistance by phosphopentomutase, and the related signaling pathway in the immune response has not been elucidated. High purity recombinant BvEP protein have no direct inhibitory effect on B. cinerea in vitro,and but induce the hypersensitivity response (HR) in Nicotiana tabacum. Tomato leaves overexpressing BvEP were found to be significantly more resistant to B. cinerea by Agrobacterium-mediated genetic transformation. Several defense genes, including WRKY28 and PTI5 of PAMP-triggered immunity (PTI), UDP and UDP1 of effector-triggered immunity (ETI), Hin1 and HSR203J of HR, PR1a of systemic acquired resistance (SAR) and the SAR related gene NPR1 were all up-regulated in transgenic tomato leaves overexpressing BvEP. In addition, it was found that transient overexpression of BvEP reduced the rotting rate and lesion diameter of tomato fruits caused by B. cinerea, and increased the expression of PTI, ETI, SAR-related genes, ROS content, SOD and POD activities in tomato fruits, while there was no significant effect on the weight loss and TSS, TA and Vc contents of tomato fruits. This study provides new insights into innovative breeding of tomato disease resistance and has great significance for loss reduction and income enhancement in the tomato industry.

High-risk neuroblastoma (NB) is sensitive to chemotherapy but susceptible to chemoresistance. In this study, we aimed to analyze the incidence of chemoresistance in high-risk NB patients and to explore the role of autophagy in NB chemoresistance. We retrospectively analyzed the incidence of changing the chemotherapy regimen due to disease stabilization or disease progression during induction chemotherapy in high-risk NB patients, which was expressed as the chemoresistance rate. The autophagy levels were probed in tumor cells exposed to first-line chemotherapy agents. The sensitivity of tumor cells to chemotherapy agents and apoptosis rate were observed after inhibiting autophagy by transfection of shRNA or chloroquine (CQ). This study included 247 patients with high-risk NB. The chemoresistance rates of patients treated with cyclophosphamide + adriamycin + vincristine (CAV) alternating with etoposide + cisplatin (EP) (Group 1) and CAV alternating with etoposide + ifosfamide + cisplatin (VIP) (Group 2) was 61.5% and 39.9% (P = 0.0009), respectively. Group 2 had better survival rates than group 1. After exposure to cisplatin, cyclophosphamide, and etoposide, the autophagy-related proteins LC3-I, LC3-II, and Beclin-1 were upregulated, and the incidence of autophagy vesicle formation and the expression of P62 were increased. Chemotherapeutic agents combined with CQ significantly increased the chemotherapeutic sensitivity of tumor cells and increased the cell apoptosis. The downregulated expression of Beclin-1 increased the sensitivity of tumor cells to chemotherapeutics. Our results suggest that increasing the chemotherapy intensity can overcome resistance to NB. Inhibition of autophagy is beneficial to increase the sensitivity of NB to chemotherapy agents.

Plasma homocysteine (Hcy) has been identified as a potential risk factor for cerebral small vessel disease. Cerebral small vessel disease (CSVD) leads to cognitive impairment, depression, and other symptoms and is a common disease in middle-aged and elderly people. To investigate the relationship between 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and CSVD in elderly patients, plasma levels of homocysteine (Hcy) and MTHFR genotyping were assessed. MRI and MRA were performed at the same time to analyze the relationship between different genotypes and cerebrovascular lesions. We showed that Hcy plasma levels in the TT group were significantly higher than those in the CC and CT groups. Moreover, we observed that the severity of white matter lesions was associated with women and positively correlated with age, previous coronary heart disease, luminal infarction, and MTHFR polymorphism. The multivariate logistic regression analysis showed that age, TT genotype, and lacunar infarction were independent risk factors for white matter hyperintensity (WMH). Importantly, we showed that there was a significant correlation between Hcy plasma levels and MTHFR gene polymorphism, with the TT genotype constituting an independent risk factor for WMH. Therefore, we recommended early detection of MTHFR gene polymorphisms with concomitant early intervention concerning risk factors to delay the occurrence of cognitive impairment in CSVD elderly patients.

In this study, we examine the regulation of wind-powered near-inertial internal waves (NIWs) in the ocean interior by mesoscale eddies, using an eddy-resolving global climate model. There is an enhancement (weakening) of NIW activity within anticyclonic (cyclonic) eddies from the surface boundary layer (SBL) base down to ~4,000 m, associated with a decreased (increased) wave vertical scale. The influence of anticyclonic eddies on NIW activity is more pronounced than that of cyclonic eddies, suggesting that the net effect of mesoscale eddies is to intensify the NIWs in the ocean interior. The enhanced (weakened) NIW activity under the SBL in anticyclonic (cyclonic) eddies is ascribed to both horizontal convergence (divergence) of NIW energy flux under the SBL and increased (decreased) downward NIW energy flux from the SBL base. The former is only confined to a layer within several hundred meters under the SBL, whereas the latter becomes dominant in the deeper ocean.

The effect of ZnO nanoparticles (ZnO NPs), with different concentrations in simulated water, on the activity of sulfate-reducing bacteria (SRB) and their adhesion behaviour on stainless-steel surfaces, with and without visible light treatment, were investigated. The results showed that the concentration of ZnO NPs and light treatment greatly influenced the antibacterial performance of the NPs. In the water solution without light treatment, the low concentration (no more than 1 mg/L) of ZnO NPs in the aqueous solution promoted the growth of SRB, and the amount of biofilm attached to the stainless-steel surface increased. As the concentration increased, ZnO NPs exhibited antibacterial effects. In water under visible light irradiation, ZnO NPs showed antibacterial performance at all the concentrations studied (0.5~50 mg/L), and the antibacterial efficiency increased with the increase in the concentration of NPs. The determination results of the reactive oxygen species showed that light treatment can stimulate ZnO NPs in water to generate ·OH and O2·−, which exhibited good antibacterial properties. The adhesion amount of SRB on the stainless-steel surface was inversely proportional to the antibacterial efficiency of ZnO NPs.

Measurement(s) Heart Rate • Galvanic Skin Response • Emotion Technology Type(s) photoplethysmography • Surface Electrode • Day Reconstruction Method • Experience Sampling Method Sample Characteristic - Organism Homo sapiens Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.13803185

Subtilisin, a serine protease, can trigger defense responses in a wide variety of plants, both locally and systemically, to protect against pathogens. However, key residues of subtilisin to improve resistance to plant diseases remain unknown. In this study, Nicotiana benthamiana (N. benthamiana) leaves expressing subtilisin from Bacillus velezensis LJ02 were shown to improve protection against Botrytis cinerea (B. cinerea). Furthermore, the underlying mechanism that LJ02 subtilisin improved the protective effect was explored, and the direct inhibitory effect of subtilisin on B. cinerea was excluded in vitro. Subsequently, reactive oxygen species (ROS) burst and upregulation of resistance-related genes in systemic leaves of N. benthamiana further verified that subtilisin could induce systemic protection against B. cinerea. G307A/T308A and S213A/L214A/G215A subtilisin significantly reduced the ability to resist B. cinerea infection in N. benthamiana. Furthermore, the ROS content and expression levels of resistance-related genes of both mutants were significantly decreased compared with that of wild-type subtilisin. This work identified key residues essential for the activation function of subtilisin plant immunity and was crucial in inducing plant defense responses against B. cinerea.