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Abstract Peritumoral hepatocytes are critical components of the liver cancer microenvironment, However, the role of peritumoral hepatocytes in the local tumor immune interface and the underlying molecular mechanisms have not been elucidated. YTHDF2, an RNA N 6 -methyladenosine (m6A) reader, is critical for liver tumor progression. The function and regulatory roles of YTHDF2 in peritumoral hepatocytes are unknown. This study demonstrated that oxaliplatin (OXA) upregulated m6A modification and YTHDF2 expression in hepatocytes. Studies using tumor-bearing liver-specific Ythdf2 knockout mice revealed that hepatocyte YTHDF2 suppresses liver tumor growth through CD8+ T cell recruitment and activation. Additionally, YTHDF2 mediated the response to immunotherapy. Mechanistically, OXA upregulated YTHDF2 expression by activating the cGAS-STING signaling pathway and consequently enhanced the therapeutic outcomes of immunotherapeutic interventions. Ythdf2 stabilized Cx3cl1 transcripts in an m6A-dependent manner, regulating the interplay between CD8+ T cells and the progression of liver malignancies. Thus, this study elucidated the novel role of hepatocyte YTHDF2, which promotes therapy-induced antitumor immune responses in the liver. The findings of this study provide valuable insights into the mechanism underlying the therapeutic benefits of targeting YTHDF2.

In the study, a hybrid lubricant was prepared by introducing graphene into a polyphosphate lubricant. In the tribological test of a steel/steel friction pair at the high temperature of 800 °C, the addition of a small proportion of graphene significantly enhances the lubrication performance of polyphosphate at elevated temperatures. The coefficient of friction and the wear were obviously held down while the surface quality of the high-temperature friction pair was enhanced effectively with the graphene-strengthened polyphosphate lubricant, compared with the dry sliding condition. Through scanning electron microscopy and Raman spectroscopy analysis, the formation mechanism of tribofilm and the antiwear performance of the hybrid lubricant are further explained. This lubricant effectively combines the advantages of both; the combination of polyphosphate melted at elevated temperature with graphene and metal surfaces ensures the self-sealing of the friction contact area and brings better high-temperature oxidation resistance. At the same time, the presence of graphene provides excellent strength to the friction film and ensures the anti-wear and wear-resistant performance of the lubricant at high temperatures.

Increasing evidence indicates that 2-hydroxyglutarate (2HG) is an oncometabolite that drives tumour formation and progression. Due to mutations in isocitrate dehydrogenase (IDH) and the dysregulation of other enzymes, 2HG accumulates significantly in tumour cells. Due to its structural similarity to α-ketoglutarate (αKG), accumulated 2HG leads to the competitive inhibition of αKG-dependent dioxygenases (αKGDs), such as KDMs, TETs, and EGLNs. This inhibition results in epigenetic alterations in both tumour cells and the tumour microenvironment. This review comprehensively discusses the metabolic pathways of 2HG and the subsequent pathways influenced by elevated 2HG levels. We will delve into the molecular mechanisms by which 2HG exerts its oncogenic effects, particularly focusing on epigenetic modifications. This review will also explore the various methods available for the detection of 2HG, emphasising both current techniques and emerging technologies. Furthermore, 2HG shows promise as a biomarker for clinical diagnosis and treatment. By integrating these perspectives, this review aims to provide a comprehensive overview of the current understanding of 2HG in cancer biology, highlight the importance of ongoing research, and discuss future directions for translating these findings into clinical applications.

IntroductionHuman gait motion intention recognition is very important for the lower extremity exoskeleton robot to accurately synchronize and respond to the user’s natural motion. And motion intention recognition is generally performed through sEMG. Deep learning neural networks perform well in dealing with high-dimensional data and nonlinear relationships such as sEMG, but different deep learning neural networks have their own advantages in dealing with different types of data. Therefore, a multi-branch deep learning neural network, which enables different neural networks to process different feature items, could achieve more accurate and efficient motion intention recognition. The purpose of this study is to 1) Establish a multi-branch deep learning neural network model to achieve accurate gait recognition and effective estimation of joint angles. 2) Quantify the performance of the multi-branch deep learning neural network model in gait recognition and joint angle prediction using sEMG.MethodologyThis study involved the collection of sEMG and plantar pressure data during walking in human subjects. Firstly, the collected signals are filtered and denoised to ensure the quality and reliability of the data. Calculate the time domain features and the frequency domain features to capture the key information of gait. Then, using the sensitivity difference of different structural neural networks to different feature data, a multi-branch deep learning neural network model is developed, in which the extracted features are used as the input of the model. The output of the model includes gait cycle and joint angle, so as to realize the accurate recognition of human gait and the effective estimation of joint angle.ResultsThe results show that the proposed method has high accuracy in identifying human gait and estimating joint angles. The multi-branch neural network model successfully integrates time-domain and frequency-domain features and provides reliable prediction of gait cycle and joint angle. The highest accuracy of gait recognition is 95.42%, the lowest is 90.11%, and the average is 92.16%. The average error of joint angle estimation is 3.19.DiscussionThis study designed a human walking gait recognition and joint angle prediction model to achieve accurate human lower limb motion intention recognition.The model can be integrated into the sEMG sensor to design a angular biosensors, which can predict the human joint angle in real time.

We propose an on-chip photoelectric hybrid convolution accelerator based on Bragg grating array. The weight of the convolution kernel can be adjusted by controlling the central wavelengths of the Bragg grating array. We conducted simulation verification of the functionality and scalability of this on-chip photoelectric hybrid convolution accelerator. Subsequently, we constructed a neural network model to conduct handwritten digit classification simulations using this accelerator, achieving a simulation accuracy of 93.99%. Finally, the concept of the proposed on-chip photoelectric hybrid convolution accelerator is successfully verified. Due to the merits of Bragg grating, the proposed scheme paves the way for realizing high-performance on-chip optical neural networks.

IntroductionCough is a common symptom of respiratory diseases, and prolonged monitoring of cough can help assist doctors in making judgments about patients’ conditions, among which cough frequency is an indicator that characterizes the state of the patient’s lungs. Therefore, the aim of this paper is to design an automatic cough counting system to monitor the number of coughs per minute for a long period of time.MethodsIn this paper, a complete cough counting process is proposed, including denoising, segment extraction, eigenvalue calculation, recognition, and counting process; and a wearable automatic cough counting device containing acquisition and reception software. The design and construction of the algorithm is based on realistically captured cough-containing audio from 50 patients, combined with short-time features, and Meier cepstrum coefficients as features characterizing the cough.ResultsThe accuracy, sensitivity, specificity, and F1 score of the method were 93.24%, 97.58%, 86.97%, and 94.47%, respectively, with a Kappa value of 0.9209, an average counting error of 0.46 counts for a 60-s speech segment, and an average runtime of 2.80 ± 2.27 s.DiscussionThis method improves the double threshold method in terms of the threshold and eigenvalues of the cough segments’ sensitivity and has better performance in terms of accuracy, real-time performance, and computing speed, which can be applied to real-time cough counting and monitoring in small portable devices with limited computing power. The developed wearable portable automatic cough counting device and the accompanying host computer software application can realize the long-term monitoring of patients’ coughing condition.

Abstract Pentamidine and melarsoprol are primary drugs used to treat the lethal human sleeping sickness caused by the parasite Trypanosoma brucei. Cross-resistance to these two drugs has recently been linked to aquaglyceroporin 2 of the trypanosome (TbAQP2). TbAQP2 is the first member of the aquaporin family described as capable of drug transport; however, the underlying mechanism remains unclear. Here, we present cryo-electron microscopy structures of TbAQP2 bound to pentamidine or melarsoprol. Our structural studies, together with the molecular dynamic simulations, reveal the mechanisms shaping substrate specificity and drug permeation. Multiple amino acids in TbAQP2, near the extracellular entrance and inside the pore, create an expanded conducting tunnel, sterically and energetically allowing the permeation of pentamidine and melarsoprol. Our study elucidates the mechanism of drug transport by TbAQP2, providing valuable insights to inform the design of drugs against trypanosomiasis.

Abstract. Background:. Patients who undergo coronary artery bypass grafting (CABG) are known to be at a significant risk of experiencing long-term adverse events, emphasizing the importance of regular assessments. Evaluating health-related quality of life (HRQoL) serves as a direct method to gauge prognosis. Our objective is to ascertain the prognostic significance of consecutive HRQoL assessments using the Physical Component Summary (PCS) and Mental Component Summary (MCS) derived from the Short-Form 36 (SF-36) health survey in CABG patients. Methods:. The study population consisted of 433 patients who underwent isolated elective CABG at Fuwai Hospital between 2012 and 2013. SF-36 assessments were conducted during both the hospitalization period and follow-up. The primary endpoint of the study was all-cause mortality, while the secondary outcome was a composite measure including death, myocardial infarction, stroke, and repeat revascularization. We assessed the relationships between the PCS and MCS at baseline, as well as their changes during the first 6 months after the surgery (referred to as ΔPCS and ΔMCS, respectively), and the observed outcomes. Results:. The patients were followed for an average of 6.28 years, during which 35 individuals (35/433, 8.1%) died. After adjusting for clinical variables, it was observed that baseline MCS scores (hazard ratio [HR] for a 1-standard deviation [SD] decrease, 1.57; 95% confidence interval [CI], 1.07–2.30) and ΔMCS (HR for a 1-SD decrease, 1.67; 95% CI, 1.09–2.56) were associated with all-cause mortality. However, baseline PCS scores and ΔPCS did not exhibit a significant relationship with all-cause mortality. Notably, there was a dose-response relationship observed between ΔMCS and the likelihood of all-cause mortality (HRs for the 2nd, 3rd and 4th quartiles compared to the 1st quartile, 0.33, 0.45 and 0.11, respectively). Conclusions:. Baseline MCS and changes in MCS were independent predictors for long-term mortality of CABG. Better mental health status and recovery indicated better prognosis.

Loess is strongly sensitive to water, and its properties are substantially affected by weathering and other factors. Loess landslides, which are widely distributed in Ili, are closely related to seasonal freeze–thaw effects. In this study, multiple freeze–thaw cycle tests were conducted on loess samples with different moisture contents from the Ili region, and triaxial shear tests were conducted to study mechanical characteristics of the loess. Variations in the microstructure of the loess samples were analysed using scanning electron microscopy images to reveal the underlying mechanisms. The results showed that the freeze–thaw cycles significantly influence failure mode of the stress–strain curve of loess samples with a lower moisture content of 10%, which transitioned from strain softening to strain hardening with six cycles as the turning point, whereas the stress–strain curve transitioned from strong to weak hardening for the loess samples with higher moisture content of 18%. As the number of freeze–thaw cycles increased, failure strength and shear strength parameters of loess gradually decreased, and tended to stabilize after the 10th cycle. In addition, strength parameters deterioration is most significant after the first cycle, and the degree of cohesion deterioration was much greater than that of internal friction angle. Cohesion and internal friction angle showed attenuation exponential function and polynomial function relationship, respectively, with the number of freeze–thaw cycles, and their fitting parameters underwent a sudden change with increasing moisture content, with 14% as the turning point. Microscopic SEM revealed that the number of overhead pores increased, and point–to–point contact between particles increased after freeze–thaw, which was consistent with increase in of loess porosity. This revealed the fundamental reason for the significant deterioration in loess strength caused by freeze–thaw cycles.

Multi-source sensor information fusion technology plays an important role in many application fields in the era of “Industry 4.0”. Generally, in practical engineering applications, the obtained information is inevitably uncertain due to the degradation of sensor performance, environmental interference, abnormal communication transmission process, etc. Compared with the strict requirements of probability density function for data quantity, the use of interval numbers to characterize the uncertainty of information has obvious advantages. Classical Dempster-Shafer(D-S) evidence theory can effectively deal with uncertain information, whereas its evidence structure is single-valued, making it difficult to fuse interval uncertainty information. Therefore, it is necessary to adopt an interval-valued evidence structure to carry out interval uncertainty information fusion. Current researches on interval-valued belief structure mainly focus on the modification of evidence combination rules but neglect the key problem of how to generate interval-valued evidence structure from original data obtained from sensors. Aiming at the problem of classification and discrimination based on multi-source interval-valued sensor information fusion, this paper adopts the theory of interval-valued evidence and focuses on the problem of generating a reasonable belief structure based on original interval-valued sensor information by using a multistage correction framework. Firstly, an interval-valued Lance and Williams Distance(ILWD) is proposed, and an initial belief structure is generated based on the proposed ILWD using the original sensor information. Secondly, by considering the interval length effect and based on Jaccard similarity coefficient, the initial interval-valued belief structure is corrected by a two-stage process. Then, in order to alleviate the impact of evidence conflict on the combination results, the weight of each evidence is assigned by an optimization method (the third stage of the belief structure modification). Further, the evidence is combined based on the method proposed by Wang et al. (2007). Finally, a practical case study is carried out to verify the rationality and effectiveness of the proposed method.

Osteoarthritis (OA) is a common chronic disease characterized by progressive cartilage degeneration and secondary synovial inflammation. Bergamottin (Ber) is an important natural derivative of the furanocoumarin compound, extracted from natural foods, such as the pulp of grapefruits and pomelos. Ber exhibits several characteristicsthat are beneficial to human health, such as anti-inflammation, antioxidant, and anti-cancer effects. However, the role of Ber in the treatment of OA has not been elucidated to date. Therefore, in the present study, in vitro experiments were conducted, which demonstrated that Ber reduces the secretion of inducible nitric oxide synthase (iNOS), nitric oxide (NO), cyclooxygenase-2 (COX2), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and prostaglandin E2 (PGE2) under the stimulation of interleukin-1β (IL-1β). Ber also reversed the IL-1 β-mediated aggrecan and type II collagen degradation within the extracellular matrix (ECM). In addition, in vivo experiments were conducted, in which Ber ameliorated the progression of OA in mice. It was revealed that Ber exerted its cellular effect by activating the Sirt1/NF-kB pathways. In conclusion, the present study demonstrated the therapeutic potential of Ber in the context of OA.

Background: Given the superior performance of various therapies over sorafenib in advanced hepatocellular carcinoma (HCC) and the absence of direct comparisons, it is crucial to explore the efficacy of these treatments in phase III randomized clinical trials. Objectives: The goal is to identify which patients are most likely to benefit significantly from these emerging therapies, contributing to more personalized and informed clinical decision-making. Design: Systematic review and network meta-analysis Data sources and methods: PubMed, Embase, ClinicalTrials.gov, and international conference databases have been searched from 1 January 2010 to 1 December 2023. Results: After screening, 17 phase III trials encompassing 18 treatments were included. In the whole-population network meta-analysis, the newly first-line tremelimumab plus durvalumab (Tre + Du) was found to be comparable with atezolizumab plus bevacizumab (Atezo + Beva) in providing the best overall survival (OS) benefit [hazard ratio (HR) 1.35, 95% confidence interval (CI): 0.93–1.92]. Concerning OS benefits, sintilimab plus bevacizumab biosimilar (Sint + Beva), camrelizumab plus rivoceranib (Camre + Rivo), and lenvatinib plus pembrolizumab (Lenva + Pemb) appear to exhibit similar effects to Tre + Du and Atezo + Beva. In the context of progression-free survival, Atezo + Beva seemed to outperform Tre + Du (HR: 0.66 CI: 0.49–0.87), while the effects are comparable to Sint + Beva, Camre + Rivo, and Lenva + Pemb. Upon comparison between Asia-Pacific and non-Asia-Pacific cohorts, as well as between hepatitis B virus (HBV)-infected and non-HBV-infected populations, immune checkpoint inhibitor (ICI)-based treatments seemed to exhibit heightened efficacy in the Asia-Pacific group and among individuals with HBV infection. However, combined ICI-based therapies did not show more effectiveness than molecular-targeted drugs in patients without macrovascular invasion and/or extrahepatic spread. As for grades 3–5 adverse events, combined therapies showed comparable safety to sorafenib and lenvatinib. Conclusion: Compared with sorafenib and lenvatinib, combination therapies based on ICIs significantly improved the prognosis of advanced HCC and demonstrated similar safety. At the same time, the optimal treatment approach should be tailored to individual patient characteristics, such as etiology, tumor staging, and serum alpha-fetoprotein levels. With lower incidence rates of treatment-related adverse events and non-inferior efficacy compared to sorafenib, ICI monotherapies should be prioritized as a first-line treatment approach for patients who are not suitable candidates for ICI-combined therapies. Trial registration: PROSPERO, CRD42022288172.

Drought stress is a major meteorological threat to crop growth and yield. Barley (Hordeum vulgare L.) is a vital cereal crop with strong drought tolerance worldwide. However, the underlying growth properties and metabolomic regulatory module of drought tolerance remains less known. Here, we investigated the plant height, spike length, effective tiller, biomass, average spikelets, 1000-grain weight, number of seeds per plant, grain weight per plant, ash content, protein content, starch content, cellulose content, and metabolomic regulation mechanisms of drought stress in barley. Our results revealed that the growth properties were different between ZDM5430 and IL-12 under drought stress at different growth stages. We found that a total of 12,235 metabolites were identified in two barley genotype root samples with drought treatment. More than 50% of these metabolites showed significant differences between the ZDM5430 and IL-12 roots. The Kyoto Encyclopedia of Genes and Genomes pathway analysis identified 368 differential metabolites mainly involved in starch and sucrose metabolism, the pentose phosphate pathway, pyrimidine metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis in ZDM5430 under drought stress, whereas the different metabolites of IL-12 under drought stress related to starch and sucrose metabolism, the pentose phosphate pathway, 2-oxocarboxylic acid metabolism, cutin, suberine and wax biosynthesis, carbon metabolism, fatty acid biosynthesis, and C5-branched dibasic acid metabolism. These metabolites have application in the tricarboxylic cycle, the urea cycle, the met salvage pathway, amino acid metabolism, unsaturated fatty acid biosynthesis, phenolic metabolism, and glycolysis. On the other hand, the expression patterns of 13 genes related to the abovementioned bioprocesses in different barley genotypes roots were proposed. These findings afford an overview for the understanding of barley roots’ metabolic changes in the drought defense mechanism by revealing the differently accumulated compounds.

Background: The functions of dendritic cells (DCs) are influenced by their intracellular metabolism, in which liver kinase B1 (LKB1) plays an important role. However, due to the difficulty in isolating the DCs, the roles of LKB1 in DC maturation and functions in tumor settings have been poorly characterized.Objective: To investigate the roles of LKB1 in DC functions including phagocytosis and presentation of antigens, activation, T cell differentiation, and ultimately tumor eradication.Methods: Genetic modification of Lkb1 in the DCs was made by lentiviral transduction, and their impacts on T cell proliferation, differentiation, activity, or B16 melanoma metastasis were examined by flow cytometry, qPCR, or lung tumor nodule counting.Results: LKB1 did not affect antigen uptake and presentation by the DCs, but facilitated the stimulation of T cell proliferation. Interestingly, following T cell activation, Foxp3-expressing regulatory T cells (Treg) were increased (P=0.0267) or decreased (P=0.0195) in mice injected with Lkb1 knockdown DCs or overexpressing DCs, respectively. Further exploration revealed that LKB1 inhibited OX40L (P=0.0385) and CD86 (P=0.0111) expression, and these co-stimulatory molecules enhanced Treg proliferation, and downregulated immune suppressive cytokine IL-10 (P=0.0315). Moreover, we found that the injection of the DCs with limited LKB1 expression before tumor inoculation could reduce their production of granzyme B (P

Hybrid two-phase closed thermosyphon (TPCT) artificial ground freezing technique is an effective cooling strategy adaptable to different geological and meteorological conditions in permafrost regions. Previous studies have focused on the feasibility of hybrid TPCT with little attention given to the cooling characteristics and long-term effects of this technique under actual environmental conditions. In this study, a novel structured semiconductor refrigeration device, with simple structure, small size, and wide operating temperature range, was designed and manufactured to act as the active condenser of a hybrid TPCT, and the cooling effect of this device was investigated during a two-year field test under stable power supply. This study showed that: 1) The minimum (maximum) average temperature of the semiconductor refrigeration two-phase closed thermosyphon (SRTPCT) evaporator was 0.5 (2.1) °C lower than the TPCT evaporator. The average ground temperature decreased by 0.3 °C, and the permafrost table rose to 0.2 m at 1 m from the evaporators around SRTPCT. The semiconductor refrigeration device added more than 9.75 MJ of cold storage to the soil around the TPCT evaporator during an operating cycle. 2) The optimal working period for the semiconductor refrigeration device was from June to October, and the cooling effect was better when the ambient temperature was low in the warm season. 3) As active condenser of hybrid TPCT in permafrost regions, semiconductor refrigeration device has a larger heat transfer power enhancement for TPCTs than vapor compression refrigeration device in the warm season, and vice versa in the cold season, as well as a higher heat transfer power enhancement for TPCTs than adsorption refrigeration device. The results of this study provide relevant parameters and references for the design and engineering application of future SRTPCT.

Single image raindrop removal aims at recovering high-resolution images from degraded ones. However, existing methods primarily employ pixel-level supervision between image pairs to learn spatial features, thus ignoring the more discriminative frequency information. This drawback results in the loss of high-frequency structures and the generation of diverse artifacts in the restored image. To ameliorate this deficiency, we propose a novel frequency-oriented Hierarchical Fusion Network (HFNet) for raindrop image restoration. Specifically, to compensate for spatial representation deficiencies, we design a dynamic adaptive frequency loss (DAFL), which allows the model to adaptively handle the high-frequency components that are difficult to recover. To handle spatially diverse raindrops, we propose a hierarchical fusion network to efficiently learn both contextual information and spatial features. Meanwhile, a calibrated attention mechanism is proposed to facilitate the transfer of valuable information. Comparative experiments with existing methods indicate the advantages of the proposed algorithm.

BackgroundN-lactoylphenylalanine (Lac-Phe) is a new form of “exerkines” closely related to lactate (La), which may be able to inhibit appetite. Blood flow restriction (BFR) can lead to local tissue hypoxia and increase lactate accumulation. Therefore, this study investigated the effects of combining Moderate-intensity Continuous Exercise (MICE) with BFR on Lac-Phe and appetite regulation in obese adults.MethodsThis study employed the cross-design study and recruited 14 obese adults aged 18-24 years. The participants were randomly divided into three groups and performed several tests with specific experimental conditions: (1) M group (MICE without BFR, 60%VO2max, 200 kJ); (2) B group (MICE with BFR, 60%VO2max, 200 kJ); and (3) C group (control session without exercise). Participants were given a standardized meal 60 min before exercise and a ad libitum 60 min after exercise. In addition, blood and Visual Analogue Scale (VAS) were collected before, immediately after, and 1 hour after performing the exercise.ResultsNo significant difference in each index was detected before exercise. After exercise, the primary differential metabolites detected in the M and B groups were xanthine, La, succinate, Lac-Phe, citrate, urocanic acid, and myristic acid. Apart from that, the major enrichment pathways include the citrate cycle, alanine, aspartate, and glutamate metabolism. The enhanced Lac-Phe and La level in the B group was higher than M and C groups. Hunger of the B group immediately after exercise substantially differed from M group. The total ghrelin, glucagon-like peptide-1 and hunger in the B group 1 hour after exercise differed substantially from M group. The results of calorie intake showed no significant difference among the indexes in each group.ConclusionsIn conclusion, this cross-design study demonstrated that the combined MICE and BFR exercise reduced the appetite of obese adults by promoting the secretion of Lac-Phe and ghrelin. However, the exercise did not considerably affect the subsequent ad libitum intake.

This research presents an augmented Kalman estimator and an equivalent replacement-based Taylor series (ERBTS)-linear quadratic Gaussian (LQG) control strategy to cope with the control accuracy and response delay of magnetorheological (MR) dampers for vehicle semi-active suspensions. The parameters in the MR model are identified from experimental measurements. Then, two main sources of control error, namely, modelling error and real-time variety of the MR damper output force, are defined as an integrated compound real-time variety. Subsequently, they are written into a differential equation with characteristics of the minimum system to augment the state equation of the semi-active suspension system. The augmented Kalman estimator is constructed to estimate the abovementioned compound real-time variety. To calculate an acceptable time-delay compensation predictive control force, an equivalent operation is implemented beforehand in the suspension comprehensive performance index by replacing a part of the squared time-delay control force with the corresponding predictive control force. Simulation results verify the effectiveness of the proposed augmented Kalman estimator, and the newly developed ERBTS-LQG controller almost achieves control effectiveness of the ideal time delay free semi-active suspension.

Introduction Despite their recent FDA(Food and Drug Administration) approval, tumour treatment fields (TTFields) have not seen acceptance as part of standard of care (SOC) for the treatment of high-grade gliomas (HGGs). Few studies have reported the clinical effect of simultaneous or sequential use of TTFields with the current SOC. However, whether TTFields are beneficial over the standard treatment remains to be established with a meta-analysis. Therefore, we here performed a systematic review and meta-analysis to understand the benefit of TTFields for patients with HGGs.Methods and analysis We registered this systematic review with the PROSPERO network (registration number: CRD42023398972) and aimed to follow the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines in the study. All articles related to TTFields in glioma will be systematically searched for in the following databases since their inception until November 2023: the China National Knowledge Infrastructure, Embase, Cochrane Library, Wanfang Database, China Science Journal Database, China Biomedical Documentation Database, VIP database, Web of Science and PubMed. Article screening and data extraction will be done independently by the authors and cross-checked by two of the authors on completion. The Cochrane risk of bias assessment tool will be used for quality assessment of the included studies. Review Manager V.5.3 (Cochrane Collaboration) will be used to perform the meta-analysis.Ethics and dissemination Ethical approval is not required because the data used will be obtained from published studies, and there will be no concerns about privacy. The results of this study will be published in a peer-reviewed journal.PROSPERO registration number CRD42023398972.

Background: Systemic chemotherapy (SC) remains the only first-line treatment for unresectable intrahepatic cholangiocarcinoma (iCCA). Hepatic arterial infusion chemotherapy (HAIC) has been recently proven to be effective in managing hepatocellular carcinoma (HCC). Hence, our study aims to investigate the safety and efficacy of HAIC in treating unresectable iCCA patients.Methods: We reviewed 146 patients with unresectable iCCA who had received HAIC or SC between March 2016 and March 2022 in a retrospective manner. Outcomes of patients and safety were compared between the HAIC and SC groups.Results: There were 75 and 71 patients in the HAIC and SC groups, respectively. The median OS in the HAIC and SC groups was 18.0 and 17.8 months (p = 0.84), respectively. The median PFS in the HAIC and SC groups was 10.8 and 11.4 months (p = 0.59), respectively. However, the HAIC group had significantly longer intrahepatic progression-free survival (IPFS) than the SC group (p = 0.035). The median IPFS in the HAIC and SC groups was 13.7 and 11.4 months, respectively. According to the OS (p = 0.047) and PFS (p = 0.009), single-tumor patients in the HAIC group appeared to benefit more. In addition, the overall incidence of adverse events (AEs) was lower in the HAIC group than that in the SC group.Conclusion: Our study revealed that HAIC was a safe and effective therapeutic regimen for unresectable iCCA with better intrahepatic tumor control when compared to SC. Meanwhile, patients with single tumor were more likely to benefit from HAIC than SC.

Abstract Background Laparoscopic liver resection (LLR) is now widely performed in treating primary liver cancer (PLC) and yields equal long-term and superior short-term outcomes to those of open liver resection (OLR). The optimal surgical approach for resectable PLC (rPLC) remains controversial. Herein, we aimed to develop a nomogram to determine the most appropriate resection approach for the individual patient. Methods Patients with rPLC who underwent hepatectomy from January 2013 to December 2018 were reviewed. Prediction model for risky surgery during LLR was constructed. Results A total of 900 patients in the LLR cohort and 423 patients in the OLR cohort were included. A history of previous antitumor treatment, tumor diameter, tumor location and resection extent were independently associated with risky surgery of LLR. The nomogram which was constructed based on these risk factors demonstrated good accuracy in predicting risky surgery with a C index of 0.83 in the development cohort and of 0.76 in the validation cohort. Patients were stratified into high-, medium- or low-risk levels for receiving LLR if the calculated score was more than 0.8, between 0.2 and 0.8 or less than 0.2, respectively. High-risk patients who underwent LLR had more blood loss (441 ml to 417 ml) and a longer surgery time (183 min to 150 min) than those who received OLR. Conclusions Patients classified into the high-risk level for LLR instead undergo OLR to reduce surgical risks and complications and patients classified into the low-risk level undergo LLR to maximize the advantages of minimally invasive surgery. Trial registration This study was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2100049446).

A parallel parking path planning method aiming at the automatic parking application scene of parallel parking in narrow space of urban roadside parking lot is proposed in the paper, based on a three-stage curve interpolation method. After the vehicle finds and detects the idle parking space through the environment perception technology, the parking path is constructed using the clothoid curve, circular arc, and fifth-degree polynomial curve by performing reverse analysis starting from the parking termination point. Considering the constraints of vehicle technical parameters and collisions avoidance during the parking process, a feasible starting area for parking is established, and the constrained optimization problem is solved to generate a path curve that satisfies curvature continuity and parking constraints. Three different parking conditions are proposed for parking simulation experiments, and the path planning method proposed in the paper (method I), the circular arc and fifth-degree polynomial curve path planning method (method II), and the fifth-degree polynomial curve path planning method (method III) are compared and analyzed. The results show that the path planning method proposed in the paper can effectively eliminate the sudden change point of curvature, constrain the path curvature and ensure the collision-free requirement for obstacles when entering the parking space for different parking spaces or different starting parking points.

BackgroundAssessment of therapeutic response of psoriasis has relied traditionally on clinical observation, and effective non-invasive tools are desirable.ObjectivesTo investigate the value of dermoscopy and high-frequency ultrasound (HFUS) in the monitoring of psoriatic lesions treated with biologics.MethodsPatients with moderate-to-severe plaque psoriasis treated with biologics were evaluated by clinical, dermoscopic, and ultrasonic scores at weeks 0, 4, 8, and 12. Clinical scores, including Psoriasis Area Severity Index (PASI) and target lesion score (TLS), were evaluated at representative lesions. Dermoscopy was performed to assess the red background, vessels, and scales on a 4-point scale as well as the presence of hyperpigmentation, hemorrhagic spots, and linear vessels. HFUS was performed to measure the thicknesses of the superficial hyperechoic band and subepidermal hypoechoic band (SLEB). The correlation between clinical, dermoscopic, and ultrasonic evaluation was also analyzed.ResultsIn total, 24 patients were analyzed and achieved 85.3 and 87.5% reduction of PASI and TLS, respectively, after 12 weeks of treatment. The red background, vessels, and scales scores under dermoscopy were reduced by 78.5, 84.1, and 86.5%, respectively. Some patients developed hyperpigmentation and linear vessels after treatment. Hemorrhagic dots slowly subside over the therapeutic course. Ultrasonic scores were significantly improved with an average reduction of 53.9% in superficial hyperechoic band thickness and 89.9% in SLEB thickness. TLS in the clinical variables, scales in dermoscopic variables, and SLEB in ultrasonic variables decreased the most significantly in the early stage of treatment (week 4) with 55.4, 57.7, and 59.1% (P > 0.05), respectively. Most of the variables, including the red background, vessels, scales, and SLEB thickness, were strongly correlated with TLS. High correlations were also found between the SLEB thickness and the red background or vessels scores, and between the superficial hyperechoic band thickness and the scales scores.ConclusionBoth dermoscopy and HFUS were useful in the therapeutic monitoring of moderate-to-severe plaque psoriasis.

Abstract Background Hearing loss has been associated with serious health problems around the globe. Previous studies have found the positive effects of fitting hearing aids on health, but few studies were conducted in developing countries. The aim of this study is to examine the effects of hearing aids on multiple health outcomes among middle-aged and older adults with hearing loss in rural China. Methods In this randomized controlled trial (RCT), participants aged 45 and above were randomly assigned to the treatment group prescribing with hearing aids or to the control group with no intervention. Trial outcomes for 385 participants were collected during the 20-month follow-up study. Using the difference-in-difference approach, our primary outcomes were hearing-related quality of life (QoL) and generic QoL. Results The intervention led to improvements in hearing-related QoL, presenting as the reduction in Hearing Handicap Inventory for the Elderly Screening Version (HHIE-S) scores (interaction coefficient = − 2.86, p = 0.005), HHIE-S-Emotional scores (interaction coefficient = − 1.42, p = 0.029), and HHIE-S-Situational scores (interaction coefficient = − 1.43, p = 0.007). The intervention was also effective in alleviating the increase in depressive symptoms (interaction coefficient = − 0.14, p = 0.042). Subgroup analysis revealed that the effects were only shown among people with social activities or active social networks. Conclusions Our study is the first RCT in China to measure the health effects and heterogeneity of hearing aid interventions. Wearing hearing aids can help improve hearing-related QoL and alleviate the increase in depressive symptoms. The intervention is expected to be applicable to similar settings in other developing countries to combat hearing-related health problems. Trial registration Chinese Clinical Trial Registry, ChiCTR1900024739 . Registered on 26 July 2019.

An elastoplastic phase field model was employed for simulations to investigate the influence of external loading on the martensitic phase transformation kinetics in steel. The phase field model incorporates external loading and plastic deformation. During the simulation process, the authenticity of the phase field model is ensured by introducing the relevant physical parameters and comparing them with experimental data. During the calculations, loads of various magnitudes and loading conditions were considered. An analysis and discussion were conducted concerning the volume fraction and phase transition temperature during the phase transformation process. The simulation results prominently illustrate the preferential orientation of variants under different loading conditions. This model can be applied to the qualitative phase transition evolution of Fe-Ni alloys, and the crystallographic parameters adhere to the volume expansion effect. It is concluded that uniaxial loading promotes martensitic phase transformation, while triaxial compressive loading inhibits it. From a dynamic perspective, it is demonstrated that external uniaxial loading accelerates the kinetics of martensitic phase transformation, with uniaxial compression being more effective in accelerating the phase transformation process than uniaxial tension. When compared to experimental data, the simulation results provide evidence that under the influence of external loading, the martensitic phase transformation is significantly influenced by the applied load, with the impact of external loading being more significant than that of plastic effects.

Low phosphorus (LP) stress leads to a significant reduction in wheat yield, primarily in the reduction of biomass, the number of tillers and spike grains, the delay in heading and flowering, and the inhibition of starch synthesis and grouting. However, the differences in regulatory pathway responses to low phosphorus stress among different wheat genotypes are still largely unknown. In this study, metabolome and transcriptome analyses of G28 (LP-tolerant) and L143 (LP-sensitive) wheat varieties after 72 h of normal phosphorus (CK) and LP stress were performed. A total of 181 and 163 differentially accumulated metabolites (DAMs) were detected for G28CK vs. G28LP and L143CK vs. L143LP, respectively. Notably, the expression of pilocarpine (C07474) in G28CK vs. G28LP was significantly downregulated 4.77-fold, while the expression of neochlorogenic acid (C17147) in L143CK vs. L143LP was significantly upregulated 2.34-fold. A total of 4023 differentially expressed genes (DEGs) were acquired between G28 and L143, of which 1120 DEGs were considered as the core DEGs of LP tolerance of wheat after LP treatment. The integration of metabolomics and transcriptomic data further revealed that the LP tolerance of wheat was closely related to 15 metabolites and 18 key genes in the sugar and amino acid metabolism pathway. The oxidative phosphorylation pathway was enriched to four ATPases, two cytochrome c reductase genes, and fumaric acid under LP treatment. Moreover, PHT1;1, TFs (ARFA, WRKY40, MYB4, MYB85), and IAA20 genes were related to the Pi starvation stress of wheat roots. Therefore, the differences in LP tolerance of different wheat varieties were related to energy metabolism, amino acid metabolism, phytohormones, and PHT proteins, and precisely regulated by the levels of various molecular pathways to adapt to Pi starvation stress. Taken together, this study may help to reveal the complex regulatory process of wheat adaptation to Pi starvation and provide new genetic clues for further study on improving plant Pi utilization efficiency.

Abstract Background Although long non-coding RNA (lncRNA) NCK1-AS1 plays important roles in human cancer, its function in atherosclerosis (AS) remains unclear. Method The expression of NCK1-AS1 in AS blood samples was detected by qRT-PCR. Oxidized low-density lipoprotein (ox-LDL) was used to construct the AS cell model, and quantitative real-time polymerase chain reaction (qRT-PCR) assay was used to evaluate NCK1-AS1 level. Cell phenotypes including proliferation and apoptosis were assessed by Cell Counting Kit-8 (CCK-8) assay and flow cytometer, respectively. The malondialdehyde level was measured to evaluate oxidative stress. The expression of apoptosis-related proteins was evaluated by western blot. The expression of inflammatory cytokines (IL-1β, IL-6 and TNK-α) was measured by qRT-PCR and ELISA assays. The relationship among NCK1-AS1, miR-1197 and COX10 was determined by bioinformatic analysis and luciferase reporter assay. Results NCK1-AS1 was significantly upregulated in AS blood samples and ox-LDL stimulated vascular smooth muscle cells (VSMCs). Knockdown of NCK1-AS1 increased cell viability, reduced cell apoptosis and MDA level, and also inhibited the expression of inflammatory cytokines (IL-1β, IL-6 and TNK-α) in ox-LDL stimulated VSMCs. NCK1-AS1 could positively regulate COX10 expression by directly sponging miR-1197. Moreover, co-transfection of sh-NCK1-AS1 and miR-1197 inhibitor, or co-transfection of sh-NCK1-AS1 and pc-COX10 (COX10 overexpressing plasmid) obviously reduced cell viability, promoted cell apoptosis, and increased MDA level in VSMCs followed by ox-LDL treatment for 24 h compared to that in sh-NCK1-AS1 transfected VSMCs. Conclusion Our study revealed that knockdown of NCK1-AS1 attenuated the development of AS by regulating miR-1197/COX10 axis, suggesting that this lncRNA might be a potential therapeutic target for AS.

Two-phase closed thermosyphons (TPCTs) have been widely used in permafrost regions because of their good cooling effect. The variation in the inclination angle of TPCTs significantly affects the heat transfer process and temperature distribution inside TPCTs, which is still not fully understood. This study experimentally investigated the heat transfer performance of TPCTs with inclination angles varied from 0° to 90° with 10° intervals. In addition to the outer wall temperature and heat flux, the thermal regime of the working medium inside TPCT was simultaneously monitored based on the core-tube. Experimental results show that the temperature distributions inside TPCT along the axial direction vary regularly with inclination angle. The heat transfer rates of the evaporator and condenser sections change nonmonotonically and nonlinearly with the inclination angle. The influence of the inclination angle on the thermal resistance is greater in the evaporator and the adiabatic sections than in the condenser section. Consequently, a TPCT at 10° produces the best heat transfer performance, corresponding to the best isothermal characteristics, the maximum heat transfer rates of the evaporator and condenser sections, and the minimum total thermal resistance. This study provides a reference of monitoring method for further research on TPCT.

Supercapacitors became more and more important recently in the area of energy storage and conversion. Their large power deliveries abilities, high stability and environmental friendliness characteristics draw tremendous attention in high-power applications such as public transit networks. Carbonaceous materials with unique surface and electrochemical properties were widely used in supercapacitors as electrode materials. This review focuses on the developments in supercapacitor electrodes made from carbonaceous materials recently, their working principle and evaluation parameters were summarized briefly. The preparation methods and electrochemical properties of different carbonaceous materials were compared and classified. It was found that the surface situation (e.g., porous structure, hydrophilic) of carbonaceous materials strongly affect the electrochemical performances of supercapacitor. So far, active carbons would be the most applicable carbonaceous electrode materials owing to their good chemical stability and conductivity, extensive accessibility inexpensiveness. But their energy densities still fall behind practical demands. Both theoretical calculations and experimental studies show that surface modification and doping of carbonaceous materials can not only optimize their pore size, structure, conductivity and surface properties, but also can introduce extra pseudocapacitance into these materials. Considering global environmental pollution and energy shortage problems nowadays, we sincerely suggested that future work should focus on domestic, medical and industrial wastes residues derived carbonaceous materials and scaled production process such as reactors and exhaust gas treatment.

The reduced inertia in the power system due to renewable energy integration introduces operation challenges in frequency stability and control. The current options for virtual inertia and frequency support are limited by the energy resources and the power electronic interface. Considering the demand on response speed and energy capacity, a general virtual synchronous machine (VSM) control based on various forms of energy storage systems (ESS) is proposed. The steady-state energy variation of energy storage is found to be proportional to the virtual damping or governor gain, while inversely proportional to the integral gain of system frequency control. It is found that the size of energy storage can be at the second time scale (for example, 6.8 p.u.·s) for VSM implementation, which is significantly smaller than the conventional hour-scale energy storage in the power system. Based on energy dynamic analysis, stability requirement, and bandwidth separation rules, an energy recovery control is designed to maintain constant state of charge (for example, 50%) while avoiding conflicts with frequency regulation. The time scale of the designed energy recovery control loop (for example, hundreds of seconds) is longer than the secondary frequency control. The effectiveness of the proposed control is verified through comprehensive case studies.

Phosphate (Pi) stress is an important environmental factor that limits plant growth and development. Of various posttranslational modifications (PTMs), protein phosphorylation and succinylation are the two most important PTMs that regulate multiple biological processes in response to Pi stress. However, these PTMs have been investigated individually but their interactions with proteins in response to Pi stress remain poorly understood. In this study, to elucidate the underlying mechanisms of protein phosphorylation and succinylation in response to Pi stress, we performed a global analysis of the barley root phosphorylome and succinylome in Pi starvation and recovery stages, respectively. A total of 3,634 and 884 unique phosphorylated and succinylated proteins, respectively, corresponding to 11,538 and 2,840 phospho- and succinyl-sites, were identified; of these, 275 proteins were found to be simultaneously phosphorylated and succinylated. Gene Set Enrichment Analysis was performed with a Kyoto Encyclopedia of Genes and Genomes pathway database revealing pathways that significantly enriched in the phosphorylome and succinylome. Such pathways, were dynamically regulated by Pi starvation and recovery treatments, and could be partitioned into distinct metabolic processes. In particular, phosphorylated proteins related to purine, the mitogen-activated protein kinase (MAPK) signaling pathway, pyrimidine, and ATP-binding cassette (ABC) transporters were upregulated in both Pi deprivation and recovery stages. Succinylated proteins, significantly upregulated by both Pi starvation and recovery, were enriched in nitrogen metabolism and phenylpropanoid biosynthesis. Meanwhile, succinylated proteins that were significantly downregulated by both Pi starvation and recovery were enriched in lysine degradation and tryptophan metabolism. This highlighted the importance of these metabolic pathways in regulating Pi homeostasis. Furthermore, protein–protein interaction network analyses showed that the response of central metabolic pathways to Pi starvation and recovery was significantly modulated by phosphorylation or succinylation, both individually and together. In addition, we discovered relevant proteins involved in MAPK signaling and phenylpropanoid biosynthetic pathways existing in interactions between phosphorylated and succinylated proteins in response to Pi recovery. The current study not only provides a comprehensive analysis of phosphorylated and succinylated proteins in plant responses to Pi starvation and recovery, but also reveals detailed interactions between phosphorylated and succinylated proteins in barley roots.

Abstract Background Hearing loss is quite prevalent and can be related to people’s quality of life. To our knowledge, there are limited studies assessing the efficacy of hearing interventions on quality of life in adults. Therefore, we aim to conduct a randomized controlled trial (RCT) to determine the impact and cost-effectiveness of community-based hearing rehabilitation on quality of life among Chinese adults with hearing loss. Methods/design In this two-arm feasibility study, participants aged 16 and above with some degree of hearing loss (n = 464) will be recruited from Linyi City, Shandong Province. They are randomly assigned to the treatment group or the control group. Those in the treatment group are prescribed with hearing aids, while those in the control group receive no intervention. Reinstruction in use of devices is provided for the treatment group during booster visits held 12 months post-randomization or unscheduled interim visits when necessary. Data are collected at baseline and the follow-up 20 months later. The primary outcome is changes in quality of life over a 20-month study period. Secondary outcomes include sub-dimensions in quality of life, physical functioning, chronic diseases, cognitive function, depression, social support, hospitalizations, falls, and healthcare costs. Finally, we will evaluate whether hearing aids intervention is cost-effective to apply in a large scale. Discussion The trial is designed to evaluate the impact and cost-effectiveness of a community-based rehabilitation intervention on quality of life among Chinese adults with hearing loss. We hope that it would help improve the well-being for Chinese adults and provide references in policy and practice for China and other countries. Trial registration Chinese Clinical Trial Registry ChiCTR1900024739 . Registered on 26 July 2019.

This research proposes an apple quality grading approach based on multi-dimensional view information processing using YOLOv5s network as the framework to rapidly and accurately perform the apple quality grading task. The Retinex algorithm is employed initially to finish picture improvement. Then, the YOLOv5s model, which is improved by adding ODConv dynamic convolution and GSConv convolution and VoVGSCSP lightweight backbone, is used to simultaneously complete the detection of apple surface defects and the identification and screening of fruit stem information, retaining only the side information of the apple multi-view. After that, the YOLOv5s network model-based approach for assessing apple quality is then developed. The introduction of the Swin Transformer module to the Resnet18 backbone increases the grading accuracy and brings the judgment closer to the global optimal solution. In this study, datasets were made using a total of 1244 apple images, each containing 8 to 10 apples. Training sets and test sets were randomly created and divided into 3:1. The experimental results demonstrated that in the multi-dimensional view information processing, the recognition accuracy of the designed fruit stem and surface defect recognition model reached 96.56% after 150 iteration training, the loss function value decreased to 0.03, the model parameter was only 6.78 M, and the detection rate was 32 frames/s. After 150 iteration training, the average grading accuracy of the quality grading model reached 94.46%, the loss function value decreased to 0.05, and the model parameter was only 3.78 M. The test findings indicate that the proposed strategy has a good application prospect in the apple grading task.

Melatonin (N-acetyl-5-methoxytryptamine) plays an important role in plant growth and development, and in the response to various abiotic stresses. However, its role in the responses of barley to low phosphorus (LP) stress remains largely unknown. In the present study, we investigated the root phenotypes and metabolic patterns of LP-tolerant (GN121) and LP-sensitive (GN42) barley genotypes under normal P, LP, and LP with exogenous melatonin (30 μM) conditions. We found that melatonin improved barley tolerance to LP mainly by increasing root length. Untargeted metabolomic analysis showed that metabolites such as carboxylic acids and derivatives, fatty acyls, organooxygen compounds, benzene and substituted derivatives were involved in the LP stress response of barley roots, while melatonin mainly regulated indoles and derivatives, organooxygen compounds, and glycerophospholipids to alleviate LP stress. Interestingly, exogenous melatonin showed different metabolic patterns in different genotypes of barley in response to LP stress. In GN42, exogenous melatonin mainly promotes hormone-mediated root growth and increases antioxidant capacity to cope with LP damage, while in GN121, it mainly promotes the P remobilization to supplement phosphate in roots. Our study revealed the protective mechanisms of exogenous MT in alleviating LP stress of different genotypes of barley, which can be used in the production of phosphorus-deficient crops.

Abstract Background Patients with cancer history are usually excluded from hepatocellular carcinoma (HCC) clinical trials. However, whether previous malignancy affects the oncological outcomes of HCC patients has not been fully assessed. This study aimed to evaluate whether prior cancer compromised the survival of HCC patients. Methods Patients with HCC were extracted from the Surveillance, Epidemiology, and End Results database between 2004 and 2015, and then they were classified into groups with and without prior cancer. The Kaplan-Meier and multivariate Cox regression analysis were adopted to evaluate whether prior cancer impacted clinical outcomes after propensity score matching (PSM) adjusting baseline differences. Validation was performed in the cohort from our institution. Results We identified 2642 HCC patients with prior cancer. After PSM, the median overall survival (OS) time were 14.5 and 12.0 months respectively for groups with and without prior cancer. Prior cancer did not compromise prognosis in patients with HCC (p = 0.49). The same tendency was found in subgroups stratified by tumor stages and cancer interval period: OS was similar between groups with and without prior cancer (both p values> 0.1). In the multivariate Cox regression model, prior cancer did not adversely impact patients’ survival (HR: 1.024; 95% CI: 0.961–1.092). In the validation cohort from our institution, prior cancer had no significant association with worse outcomes (p = 0.48). Conclusion For HCC patients, prior cancer did not compromise their survival, regardless of tumor stage and cancer interval period. Exclusion criteria for HCC clinical trials could be reconsidered.

The multi-region integrated energy system (MRIES) is one promising option for exploiting the complementarity potentials between power system, thermal system and loads, as well as improving flexibility and economic competitiveness. However, the optimal planning has remained challenging since it involves multiple forms of energies with the nature of coupling. A mixed integer linear programming (MILP) model is proposed for joint optimization of MRIES planning and operation, which considers the flexible load’s demand response (DR). It is realized by combining the multi-region heating network IES coupling model with the flexible cooling-heating-electric load DR model. The results show that the proposed model can assist planners to comprehensively analyze and evaluate the impacts of multiple factors on planning, and to determine the optimal planning configuration and operation strategy.

Abstract As natural nanoparticles, exosomes are a type of extracellular vesicles that are enclosed by a lipid bilayer and contain various cargos, including miRNA, mRNA, DNA and proteins. Exosomes have rapidly gained attention as a highly promising cell-free therapy. Because the cargo of exosomes changes with the changes in parent cells and status, exosomes from different types of cells may exhibit different biological effects. Considering the particularity of oral tissue stem cells, their exosomes were isolated and used to examine their related biological functions and the possibility of replacing stem cells. A variety of exosomes of oral tissue stem cells were studied, and the results revealed many special biological characteristics of these exosomes and their parent cells, especially immunomodulation, osteogenesis, odontogenesis, neuroprotection, nerve regeneration, wound healing, skin regeneration and vascularization. The oral tissue stem cell exosomes may be loaded with drugs or genes and act as tools for tumor treatment. The relevant results showed that exosomes from oral tissue stem cells were potent therapeutic tools. The present review focuses on the biological function and application of oral tissue stem cell-derived exosomes.

Nitrogen is one of the most important mineral elements for plant growth and development. Excessive nitrogen application not only pollutes the environment, but also reduces the quality of crops. However, are few studies on the mechanism of barley tolerance to low nitrogen at both the transcriptome and metabolomics levels. In this study, the nitrogen-efficient genotype (W26) and the nitrogen-sensitive genotype (W20) of barley were treated with low nitrogen (LN) for 3 days and 18 days, then treated with resupplied nitrogen (RN) from 18 to 21 days. Later, the biomass and the nitrogen content were measured, and RNA-seq and metabolites were analyzed. The nitrogen use efficiency (NUE) of W26 and W20 treated with LN for 21 days was estimated by nitrogen content and dry weight, and the values were 87.54% and 61.74%, respectively. It turned out to have a significant difference in the two genotypes under the LN condition. According to the transcriptome analysis, 7926 differentially expressed genes (DEGs) and 7537 DEGs were identified in the leaves of W26 and W20, respectively, and 6579 DEGs and 7128 DEGs were found in the roots of W26 and W20, respectively. After analysis of the metabolites, 458 differentially expressed metabolites (DAMs) and 425 DAMs were found in the leaves of W26 and W20, respectively, and 486 DAMs and 368 DAMs were found in the roots of W26 and W20, respectively. According to the KEGG joint analysis of DEGs and DAMs, it was discovered that glutathione (GSH) metabolism was the pathway of significant enrichment in the leaves of both W26 and W20. In this study, the metabolic pathways of nitrogen metabolism and GSH metabolism of barley under nitrogen were constructed based on the related DAMs and DEGs. In leaves, GSH, amino acids, and amides were the main identified DAMs, while in roots, GSH, amino acids, and phenylpropanes were mainly found DAMs. Finally, some nitrogen-efficient candidate genes and metabolites were selected based on the results of this study. The responses of W26 and W20 to low nitrogen stress were significantly different at the transcriptional and metabolic levels. The candidate genes that have been screened will be verified in future. These data not only provide new insights into how barley responds to LN, but also provide new directions for studying the molecular mechanisms of barley under abiotic stress.

Tsunamis can cause high numbers of casualties, as well as direct and indirect economic losses to coastal regions. The huge destructiveness of tsunamis requires us to study tsunami risk and its temporal change. We adopt the tsunami scenarios of the Ryukyu Trench as an example to analyze the temporal change in tsunami risk. According to the tsunami numerical model results, the tsunami inundation in the worst tsunami scenario covered an area of 82.83 km2. Satellite data including Landsat 8 images from July 2013 and Landsat 9 images from March 2022 were used with the random forest (RF) method to analyze land use and tsunami vulnerability in 2013 and 2022. The tsunami risk and its temporal change were analyzed by integrating tsunami hazard and tsunami vulnerability. The tsunami risk change analysis results show that the area of tsunami risk level 1 increased by 4.57 km2, and the area of tsunami risk level 4 decreased by 7.31 km2. By analyzing changes in land use and land cover (LULC) and tsunami risk, we concluded that the expansion of constructed land and the increase in coastal population were responsible for the increase in tsunami risk. The results of tsunami risk change analysis will help us understand the current tsunami risk and predict possible future risk change. In addition, it is necessary to prepare tsunami prevention measures in advance and produce tsunami emergency response plans for Qidong County and other regions under potential tsunami threat.

Apple grading is an essential part of the apple marketing process to achieve high profits. In this paper, an improved YOLOv5 apple grading method is proposed to address the problems of low grading accuracy and slow grading speed in the apple grading process and is experimentally verified by the designed automatic apple grading machine. Firstly, the Mish activation function is used instead of the original YOLOv5 activation function, which allows the apple feature information to flow in the deep network and improves the generalization ability of the model. Secondly, the distance intersection overUnion loss function (DIoU_Loss) is used to speed up the border regression rate and improve the model convergence speed. In order to refine the model to focus on apple feature information, a channel attention module (Squeeze Excitation) was added to the YOLOv5 backbone network to enhance information propagation between features and improve the model’s ability to extract fruit features. The experimental results show that the improved YOLOv5 algorithm achieves an average accuracy of 90.6% for apple grading under the test set, which is 14.8%, 11.1%, and 3.7% better than the SSD, YOLOv4, and YOLOv5s models, respectively, with a real-time grading frame rate of 59.63 FPS. Finally, the improved YOLOv5 apple grading algorithm is experimentally validated on the developed apple auto-grader. The improved YOLOv5 apple grading algorithm was experimentally validated on the developed apple auto grader. The experimental results showed that the grading accuracy of the automatic apple grader reached 93%, and the grading speed was four apples/sec, indicating that this method has a high grading speed and accuracy for apples, which is of practical significance for advancing the development of automatic apple grading.

Summary: Immune checkpoint blockade (ICB) persistently provides a prognosis improvement but only in a small fraction of patients with cancer due to immunotherapy resistance induced by the consecutive activated oncogenic pathways, including MAPK, Akt, and WNT pathway partially driven by Metadherin (MTDH). However, there is no study to investigate the potential role and mechanisms of MTDH in ICB-treated cancers. Here, we systematically explored the cohorts from The Cancer Genome Atlas (TCGA) and independent cancer cohorts. Elevated MTDH expression was founded to associate with a worse overall survival and poorer immune response in patients with cancer. Dysregulated tumor-infiltrating immune cells and inhibitory immune checkpoint expression were correlated with MTDH expression. Furthermore, the mutual interactions between epithelial-to-mesenchymal-transition, m6A-RNA-methylation, and MTDH may illustrate the potential mechanisms of MTDH resistant to ICB treatment. Although more designed experiments and trials are needed in the future, targeting MTDH may help to overcome immunotherapy resistance in a wide range of cancers.

Cuticular waxes comprise the hydrophobic layer that protects crops against nonstomatal water loss and biotic and abiotic stresses. Expanding on our current knowledge of the genes that are involved in cuticular wax biosynthesis and regulation plays an important role in dissecting the processes of cuticular wax metabolism. In this study, we identified the Cer-GN1 barley (Hordeum vulgare L.) mutant that is generated by ethyl methanesulfonate mutagenesis with a glossy spike phenotype that is controlled by a single recessive nuclear gene. A physiological analysis showed that the total cuticular wax loads of Cer-GN1 were one-third that of the progenitor wild-type (WT), and its water loss rate was significantly accelerated (p < 0.05). In addition, Cer-GN1 was defective in the glume’s cuticle according to the toluidine blue dye test, and it was deficient in the tubule-shaped crystals which were observed on the glume surfaces by scanning electron microscopy. Using metabolomics and transcriptomics, we investigated the impacts of cuticular wax composition and waxy regulatory genes on the loss of the glaucous wax in the spikes of Cer-GN1. Among the differential metabolites, we found that 16-hydroxyhexadecanoic acid, which is one of the predominant C16 and C18 fatty acid-derived cutin monomers, was significantly downregulated in Cer-GN1 when it was compared to that of WT. We identified two novel genes that are located on chromosome 4H and are downregulated in Cer-GN1 (HvMSTRG.29184 and HvMSTRG.29185) that encode long-chain fatty acid omega-monooxygenase CYP704B1, which regulates the conversion of C16 palmitic acid to 16-hydroxyhexadecanoic acid. A quantitative real-time PCR revealed that the expression levels of HvMSTRG.29184 and HvMSTRG.29185 were downregulated at 1, 4, 8, 12, and 16 days after the heading stage in Cer-GN1 when it was compared to those of WT. These results suggested that HvMSTRG.29184 and HvMSTRG.29185 have CYP704B1 activity, which could regulate the conversion of C16 palmitic acid to 16-hydroxyhexadecanoic acid in barley. Their downregulation in Cer-GN1 reduced the synthesis of the cuticular wax components and ultimately caused the loss of the glaucous wax in the spikes. It is necessary to verify whether HvMSTRG.29184 and HvMSTRG.29185 truly encode a CYP704B1 that regulates the conversion of C16 palmitic acid to 16-hydroxyhexadecanoic acid in barley.

Salt stress is a major abiotic stress factor affecting crop production, and understanding of the response mechanisms of seed germination to salt stress can help to improve crop tolerance and yield. The differences in regulatory pathways during germination in different salt-tolerant barley seeds are not clear. Therefore, this study investigated the responses of different salt-tolerant barley seeds during germination to salt stress at the proteomic and metabolic levels. To do so, the proteomics and metabolomics of two barley seeds with different salt tolerances were comprehensively examined. Through comparative proteomic analysis, 778 differentially expressed proteins were identified, of which 335 were upregulated and 443 were downregulated. These proteins, were mainly involved in signal transduction, propanoate metabolism, phenylpropanoid biosynthesis, plant hormones and cell wall stress. In addition, a total of 187 salt-regulated metabolites were identified in this research, which were mainly related to ABC transporters, amino acid metabolism, carbohydrate metabolism and lipid metabolism; 72 were increased and 112 were decreased. Compared with salt-sensitive materials, salt-tolerant materials responded more positively to salt stress at the protein and metabolic levels. Taken together, these results suggest that salt-tolerant germplasm may enhance resilience by repairing intracellular structures, promoting lipid metabolism and increasing osmotic metabolites. These data not only provide new ideas for how seeds respond to salt stress but also provide new directions for studying the molecular mechanisms and the metabolic homeostasis of seeds in the early stages of germination under abiotic stresses.

Torsional vibration of the automotive driveline has significant influence on driving comfort. This study investigates the influence of clutch nonlinear behaviors on the torsional vibration of the driveline with numerical and experimental methods. A generic automobile powertrain model with 7 degrees of freedom is proposed considering the transient engine torque, the nonlinear characteristics of multi-stage clutch and tire slip. Taking a commercial vehicle as an example, the dynamic behaviors and inherent characteristics of the driveline system are calculated and analyzed. Based on the proposed model, the influences of the clutch parameters on driveline torsional vibration are investigated. In order to validate the proposed model and the analytical results, an optimized clutch is designed and the experiments of torsional vibration are conducted with the prototype and the optimized clutch. The analytical and experimental results demonstrate that an increase in the first end-stop angle and the main-stage hysteresis or a decrease in the second end-stop angle and the main-stage stiffness of the clutch can effectively suppress driveline torsional vibration during vehicle accelerating.

Halogeton glomeratus is a succulent annual herbaceous halophyte belonging to the Chenopodiaceae family, has attracted wide attention as a promising candidate for phytoremediation and as an oilseed crop and noodle-improver. More importantly, H. glomeratus has important medicinal value in traditional Chinese medicine. However, there are few comprehensive studies on the nutrients, particularly secondary metabolites. Here, we adopted untargeted metabolomics to compare the differences in metabolites of different tissues (root, stem, leaf, and seed) and identify the compounds related to pharmacological effects and response to abiotic stress in H. glomeratus. A total of 2,152 metabolites were identified, and the metabolic profiles of root, stem, leaf, and seed samples were clearly separated. More than 50% of the metabolites showed significant differences among root, stem, leaf, and seed. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of differential metabolites suggested an extensive alteration in the metabolome among the different organs. Furthermore, the identified metabolites related to pharmacological effects and response to abiotic stress included flavones, flavonols, flavandiols, glucosinolates, isoquinolines, pyridines, indoles, amino acids, lipids, carbohydrates, and ATP-binding cassette transporters. These metabolites have application in treating human cardiovascular diseases, cancers, diabetes, and heart disease, induce sleeping and have nutritive value. In plants, they are related to osmotic adjustment, alleviating cell damage, adjusting membrane lipid action and avoiding toxins. To the best of our knowledge, this is the first metabolomics-based report to overview the metabolite compounds in H. glomeratus and provide a reference for future development and utilization of H. glomeratus.

Phosphorus (P) deficiency is a major threat to the crop production, and for understanding the response mechanism of plant roots, P stress may facilitate the development of crops with increased tolerance. Phosphorylation plays a critical role in the regulation of proteins for plant responses to biotic and abiotic stress; however, its functions in P starvation/resupply are largely unknown for barley (Hordeum vulgare) growth. Here, we performed a global review of phosphorylation in barley roots treated by P starvation/resupply. We identified 7,710 phosphorylation sites on 3,373 proteins, of which 76 types of conserved motifs were extracted from 10,428 phosphorylated peptides. Most phosphorylated proteins were located in the nucleus (36%) and chloroplast (32%). Compared with the control, 186 and 131 phosphorylated proteins under P starvation condition and 156 and 111 phosphorylated proteins under P resupply condition showed significant differences at 6 and 48 h, respectively. These proteins mainly participated in carbohydrate metabolism, phytohormones, signal transduction, cell wall stress, and oxidases stress. Moreover, the pathways of the ribosome, RNA binding, protein transport, and metal binding were significantly enriched under P starvation, and only two pathways of ribosome and RNA binding were greatly enriched under Pi resupply according to the protein–protein interaction analysis. The results suggested that the phosphorylation proteins might play important roles in the metabolic processes of barley roots in response to Pi deficiency/resupply. The data not only provide unique access to phosphorylation reprogramming of plant roots under deficiency/resupply but also demonstrate the close cooperation between these phosphorylation proteins and key metabolic functions.

In order to enable the picking robot to detect and locate apples quickly and accurately in the orchard natural environment, we propose an apple object detection method based on Shufflenetv2-YOLOX. This method takes YOLOX-Tiny as the baseline and uses the lightweight network Shufflenetv2 added with the convolutional block attention module (CBAM) as the backbone. An adaptive spatial feature fusion (ASFF) module is added to the PANet network to improve the detection accuracy, and only two extraction layers are used to simplify the network structure. The average precision (AP), precision, recall, and F1 of the trained network under the verification set are 96.76%, 95.62%, 93.75%, and 0.95, respectively, and the detection speed reaches 65 frames per second (FPS). The test results show that the AP value of Shufflenetv2-YOLOX is increased by 6.24% compared with YOLOX-Tiny, and the detection speed is increased by 18%. At the same time, it has a better detection effect and speed than the advanced lightweight networks YOLOv5-s, Efficientdet-d0, YOLOv4-Tiny, and Mobilenet-YOLOv4-Lite. Meanwhile, the half-precision floating-point (FP16) accuracy model on the embedded device Jetson Nano with TensorRT acceleration can reach 26.3 FPS. This method can provide an effective solution for the vision system of the apple picking robot.

Barley (Hordeum vulgare L.)—a major cereal crop—has low Pi demand, which is a distinct advantage for studying the tolerance mechanisms of phosphorus deficiency. We surveyed dynamic protein succinylation events in barley roots in response to and recovery from Pi starvation by firstly evaluating the impact of Pi starvation in a Pi-tolerant (GN121) and Pi-sensitive (GN42) barley genotype exposed to long-term low Pi (40 d) followed by a high-Pi recovery for 10 d. An integrated proteomics approach involving label-free, immune-affinity enrichment, and high-resolution LC-MS/MS spectrometric analysis was then used to quantify succinylome and proteome in GN121 roots under short-term Pi starvation (6, 48 h) and Pi recovery (6, 48 h). We identified 2,840 succinylation sites (Ksuc) across 884 proteins; of which, 11 representative Ksuc motifs had the preferred amino acid residue (lysine). Furthermore, there were 81 differentially abundant succinylated proteins (DFASPs) from 119 succinylated sites, 83 DFASPs from 110 succinylated sites, 93 DFASPs from 139 succinylated sites, and 91 DFASPs from 123 succinylated sites during Pi starvation for 6 and 48 h and during Pi recovery for 6 and 48 h, respectively. Pi starvation enriched ribosome pathways, glycolysis, and RNA degradation. Pi recovery enriched the TCA cycle, glycolysis, and oxidative phosphorylation. Importantly, many of the DFASPs identified during Pi starvation were significantly overexpressed during Pi recovery. These results suggest that barley roots can regulate specific Ksuc site changes in response to Pi stress as well as specific metabolic processes. Resolving the metabolic pathways of succinylated protein regulation characteristics will improve phosphate acquisition and utilization efficiency in crops.