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Heading date determines rice seasonal and regional adaptation, while plant height is an important trait related to rice lodging resistance. In this study, a recombinant inbred line population was used to detect quantitative trait loci (QTLs) for both traits in long-day (LD) and short-day (SD) environments. Three and two QTLs for heading date were detected in LD and SD environments, respectively. Notably, qHD8 and qHD10 were commonly detected in both environments. Five and four QTLs for plant height were identified in LD and SD environments, respectively. Among them, qPH3, qPH5 and qPH6 showed no pleiotropic effects on heading date and were detected in both environments. These three QTLs are considered to be the primary targets for improving rice plant height. Additionally, two genomic regions exhibited pleiotropic effects on both heading date and plant height. The alleles delayed the heading date while simultaneously increasing plant height. This study indicated that most QTLs for heading date are sensitive to photoperiod and have pleiotropic effects on plant height, thereby complicating their application in breeding programs. These findings provide useful information for the breeding of rice varieties with desired heading dates and plant heights.

Abstract Purpose To develop a radiomics-based model using [68Ga]Ga-PSMA PET/CT to predict postoperative adverse pathology (AP) in patients with biopsy Gleason Grade Group (GGG) 1–2 prostate cancer (PCa), assisting in the selection of patients for active surveillance (AS). Methods A total of 75 men with biopsy GGG 1–2 PCa who underwent radical prostatectomy (RP) were enrolled. The patients were randomly divided into a training group (70%) and a testing group (30%). Radiomics features of entire prostate were extracted from the [68Ga]Ga-PSMA PET scans and selected using the minimum redundancy maximum relevance algorithm and the least absolute shrinkage and selection operator regression model. Logistic regression analyses were conducted to construct the prediction models. Receiver operating characteristic (ROC) curve, decision curve analysis (DCA), and calibration curve were employed to evaluate the diagnostic value, clinical utility, and predictive accuracy of the models, respectively. Results Among the 75 patients, 30 had AP confirmed by RP. The clinical model showed an area under the curve (AUC) of 0.821 (0.695–0.947) in the training set and 0.795 (0.603–0.987) in the testing set. The radiomics model achieved AUC values of 0.830 (0.720–0.941) in the training set and 0.829 (0.624–1.000) in the testing set. The combined model, which incorporated the Radiomics score (Radscore) and free prostate-specific antigen (FPSA)/total prostate-specific antigen (TPSA), demonstrated higher diagnostic efficacy than both the clinical and radiomics models, with AUC values of 0.875 (0.780–0.970) in the training set and 0.872 (0.678–1.000) in the testing set. DCA showed that the net benefits of the combined model and radiomics model exceeded those of the clinical model. Conclusion The combined model shows potential in stratifying men with biopsy GGG 1–2 PCa based on the presence of AP at final pathology and outperforms models based solely on clinical or radiomics features. It may be expected to aid urologists in better selecting suitable patients for AS.

Multifunctional therapeutics have emerged as a solution to the constraints imposed by drugs with singular or insufficient therapeutic effects. The primary challenge is to integrate diverse pharmacophores within a single-molecule framework. To address this, we introduced DeepSA, a novel edit-based generative framework that utilizes deep simulated annealing for the modification of articaine, a well-known local anesthetic. DeepSA integrates deep neural networks into metaheuristics, effectively constraining molecular space during compound generation. This framework employs a sophisticated objective function that accounts for scaffold preservation, anti-inflammatory properties, and covalent constraints. Through a sequence of local editing to navigate the molecular space, DeepSA successfully identified AT-17, a derivative exhibiting potent analgesic properties and significant anti-inflammatory activity in various animal models. Mechanistic insights into AT-17 revealed its dual mode of action: selective inhibition of NaV1.7 and 1.8 channels, contributing to its prolonged local anesthetic effects, and suppression of inflammatory mediators via modulation of the NLRP3 inflammasome pathway. These findings not only highlight the efficacy of AT-17 as a multifunctional drug candidate but also highlight the potential of DeepSA in facilitating AI-enhanced drug discovery, particularly within stringent chemical constraints.

Connective tissue diseases-related pulmonary arterial hypertension (CTD-PAH) is a disease characterized by an elevated pulmonary artery pressure that arises as a complication of connective tissue diseases. The number of patients with CTD-PAH accounts for 25.3% of all PAH patients. The main pathological features of CTD-PAH are thickening of intima, media and adventitia of pulmonary arterioles, increased pulmonary vascular resistance, autoimmune activation and inflammatory reaction. It is worth noting that abnormal immune activation will produce autoantibodies and release cytokines, and abnormal immune cell recruitment will promote inflammatory environment and vascular remodeling. Therefore, almost all forms of connective tissue diseases are related to PAH. In addition to general therapy and targeted drug therapy for PAH, high-dose glucocorticoid combined with immunosuppressant can quickly alleviate and stabilize the basic CTD-PAH disease. Given this, the development of therapeutic approaches targeting immune dysregulation and heightened inflammation is recognized as a promising strategy to prevent or reverse the progression of CTD-PAH. This review explores the potential mechanisms by which immune cells contribute to the development of CTD-PAH and examines the clinical application of immunosuppressive therapies in managing CTD-PAH.

Alzheimer's disease (AD) presents a significant challenge due to its prevalence and lack of cure, driving the quest for effective treatments. Anshen Bunao Syrup, a traditional Chinese medicine known for its neuroprotective properties, shows promise in addressing this need. However, understanding its precise mechanisms in AD remains elusive. This study aimed to investigate Anshen Bunao Syrup's therapeutic potential in AD treatment using a scopolamine-induced AD rat model. Assessments included novel-object recognition and Morris water maze tasks to evaluate spatial learning and memory, alongside Nissl staining and ELISA analyses for neuronal damage and biomarker levels. Results demonstrated that Anshen Bunao Syrup effectively mitigated cognitive dysfunction by inhibiting amyloid-β and phosphorylation Tau aggregation, thereby reducing neuronal damage. Metabolomics profiling of rats cortex revealed alterations in key metabolites implicated in tryptophan and fatty acid metabolism pathways, suggesting a role in the therapeutic effects of Anshen Bunao Syrup. Additionally, ELISA and correlation analyses indicated attenuation of oxidative stress and immune response through metabolic remodeling. In conclusion, this study provides compelling evidence for the neuroprotective effects of Anshen Bunao Syrup in AD models, shedding light on its potential as a therapeutic agent for AD prevention and treatment.

Abstract Background Ferroptosis, a non-apoptotic form of cell death induced by accumulation of free iron ions and lipid peroxidation, its importance for cancer treatment is gradually being recognized. Research on the anti-cancer mechanism of juglone is accumulating. However, the specific mechanism by which it directs glioblastoma (GBM) to death is unknown. Methods We used in vitro and in vivo experiments to explore the anti-GBM effect generated by juglone through the ferroptosis pathway. Results Juglone mainly causes cell death by inducing ferroptosis. Mechanistically, juglone can significantly activate the phosphorylation of p38MAPK. According to transcriptome sequencing and protein interaction analysis, the Nrf2-GPX4 signaling pathway is identified as the primary pathway through which juglone mediates ferroptosis. In vitro and in vivo experiments further verified that juglone induces the ferroptosis of GBM by activating the phosphorylation of p38MAPK and negatively regulating the Nrf2-GPX4 signaling pathway. Conclusion Juglone induces ferroptosis and inhibits the growth of GBM by targeting the Nrf2/Gpx4 signaling pathway and thus holds promise as a novel ferroptosis inducer or anti-GBM drug.

Abstract Hepatocellular carcinoma (HCC) is significantly associated with adverse prognostic outcomes. The development and progression of different types of human tumors are significantly influenced by APOB. Nevertheless, the significance and pathomechanisms of APOB in HCC have not been conclusively determined. We assessed APOB expression levels in HCC using three publicly available databases of TIMER2.0, UALCAN and Human Protein Atlas. To identify the biological function of APOB, we conducted enrichment analysis via LinkedOmics. Moreover, UALCAN was employed to assess the relationship between APOB expression and clinicopathological features among HCC patients. Additionally, the Kaplan–Meier plotter was utilized to investigate the prognostic relevance of APOB in HCC. To explore potential regulatory ncRNAs that could bind to APOB, we utilized StarBase and GEPIA. Furthermore, the correlation between APOB expression and immune cell infiltration, as well as immune checkpoint genes, was investigated using Spearman's correlation analysis in TISIDB, GEPIA, and TIMER2.0. The findings of our investigation showed a notable decrease in the expression levels of APOB among individuals diagnosed with HCC. Moreover, a noteworthy correlation was observed between the expression of APOB and immune checkpoint genes, alongside the occurrence of immune cell infiltration. The levels of APOB expression in HCC tissues also showed correlations with various clinicopathological features. According to Cox regression analysis, decreased APOB expression emerged as a potential autonomous predictor for OS, RFS, DSS, and PFS among HCC patients. Furthermore, we identified six potential pathways associated with non-coding RNA (ncRNA) as the most promising pathway for APOB in HCC. Our results illuminate the possible involvement of APOB in HCC and offer understanding into its governing mechanisms and medical importance.

Plant-parasitic nematodes (PPNs) are among the most damaging pathogens to host plants. Plants can modulate their associated bacteria to cope with nematode infections. The tritrophic plant–nematode–microbe interactions are highly taxa-dependent, resulting in the effectiveness of nematode agents being variable among different host plants. Ficus tikoua is a versatile plant with high application potential for fruits or medicines. In recent years, a few farmers have attempted to cultivate this species in Sichuan, China, where parasitic nematodes are present. We used 16S rRNA genes to explore the effects of nematode parasitism on root-associated bacteria in this species. Our results revealed that nematode infection had effects on both endophytic bacterial communities and rhizosphere communities in F. tikoua roots, but on different levels. The species richness increased in the rhizosphere bacterial communities of infected individuals, but the community composition remained similar as compared with that of healthy individuals. Nematode infection induces a deterministic assembly process in the endophytic bacterial communities of parasitized organs. Significant taxonomic and functional changes were observed in the endophytic communities of root knots. These changes were characterized by the enrichment of nitrogen-fixing bacteria, including Bradyrhizobium, Allorhizobium–Neorhizobium–Pararhizobium–Rhizobium, and nematode-antagonistic bacteria, such as Pseudonocardia, Pseudomonas, Steroidobacter, Rhizobacter, and Ferrovibrio. Our results would help the understanding of the tritrophic plant–nematode–bacterium interactions in host plants other than dominant crops and vegetables and would provide essential information for successful nematode management when F. tikoua were cultivated on large scales.

Hundreds of scientific documents have reported on the application of indocyanine green (ICG) in hepatobiliary surgery in the past 13 years, but few bibliometric studies have been conducted. This study aimed to identify the situations of authors, countries/regions, institutions, journals, and hot topics in this field. The overall status and prospects of the current research in this field can be elucidated by bibliometric analysis. Publications from 2008 to 2021 were retrieved from the Web of Science (WoS) Core Collection. The search terms included “liver,” “hepatic,” “gallbladder,” “bile duct,” “surgery,” “hepatectomy,” “ICG,” “indocyanine green,” and related synonyms. The full records of the search results were exported in text, and the cooperation network and hot topics were evaluated and visualized using CiteSpace software. The number of publications increased between 2008 and 2021. A total of 1527 publications were included in the results, and the frequency of citations was 30,742. The largest proportion of the publications emanated from Japan, and the majority of the papers were published by Kokudo. Tian Jie contributed the largest number of papers in China. Research was relatively concentrated among one country/region. The latest hotspots, “preservation” and “resistance”, frequently occurred. Cooperation between authors, countries, and institutions needs to be strengthened for high-quality research. Recent studies have focused on hepatectomy, bile duct resection, liver transplantation, and tumors in this field. Future research may focus on other aspects, such as liver preservation and resistance.

Prostate adenocarcinoma (PRAD), driven by both genetic and epigenetic factors, is a common malignancy that affects men worldwide. We aimed to identify and characterize differentially expressed epigenetic-related genes (ERGs) in PRAD and investigate their potential roles in disease progression and prognosis. We used PRAD samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to identify prognosis-associated ERGs. Thirteen ERGs with two distinct expression profiles were identified through consensus clustering. Gene set variation analysis highlighted differences in pathway activities, particularly in the Hedgehog and Notch pathways. Higher epigenetic scores correlated with favorable prognosis and improved immunotherapeutic response. Experimental validation underscored the importance of CBX3 and KAT2A, suggesting their pivotal roles in PRAD. This study provides crucial insights into the epigenetic scoring approach and presents a promising prognostic tool, with CBX3 and KAT2A as key players. These findings pave the way for targeted and personalized interventions for the treatment of PRAD.

The performance of a semi-active suspension depends on the quality of the control algorithm. Considering the limitations of conventional PID controllers within intricate nonlinear systems, such as imprecise parameter tuning and performance deterioration, we introduced a fractional-order PID (FOPID) control strategy for vehicle semi-active suspension, this approach amalgamates fractional-order theory with conventional PID control to enhance both the controllable scope and precision of the suspension system. Research on semi-active suspension control was conducted using a nonlinear dynamic model of a quarter vehicle. Simulations and analyses were performed utilizing random road excitation and impact road excitation as input signals for both FOPID control, Fuzzy-PID control, and conventional PID control strategies. The analysis findings demonstrated that in the presence of random road excitation, the semi-active suspension system controlled by FOPID reduced vehicle body acceleration by 18.9%, in contrast to a 14.7% reduction by the Fuzzy-PID-controlled suspension, and a 12% reduction achieved by the PID-controlled suspension when compared to the passive suspension. In response to impact road excitation, the suspension system under FOPID control effectively mitigated the peak value of vehicle body acceleration by 29.4%, surpassing the 25.2% reduction achieved by Fuzzy-PID-controlled suspension, and the 24.6% reduction achieved by the PID-controlled suspension. The simulation outcomes substantiated that ride comfort and handling stability of the semi-active suspension system were effectively improved by the implementation of FOPID control.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease, often diagnosed at an advanced stage. Systemic chemotherapy is the primary treatment, but direct comparisons of different regimens are limited. This study conducted a systematic review and network meta-analysis (NMA) to compare the efficacy and safety of various chemotherapy regimens, with the unique advantage of only including Phase III randomized controlled trials (RCTs). Methods: NMA was conducted regarding the searched phase III RCTs by comparing overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs) of different chemotherapy protocols. Results: The analysis included 24 studies with 11470 patients across 25 treatment modalities. Among the chemotherapy regimens evaluated, FOLFIRINOX (fluorouracil, leucovorin, irinotecan, and oxaliplatin) demonstrated the highest OS and PFS, with a risk ratio (logHR) of 4.5 (95 % confidence interval 4.32–4.68) compared to gemcitabine monotherapy. The PEFG regimen (cisplatin, epirubicin, 5-fluorouracil, and gemcitabine) exhibited the highest ORR, with an odds ratio (OR) of 6.67 (2.08–20) compared to gemcitabine monotherapy. Notably, gemcitabine plus sorafenib was associated with the lowest hematological toxicity, with an odds ratio (OR) of 0.1 (0.02–0.48). Conclusion: Combination therapies may offer greater benefits but also cause more toxic effects. However, combinations with targeted agents seem to have fewer adverse reactions.

Artificial intelligence (AI) has played a critical role in the enhancement and automation of global food production and delivery. The assessment of ripeness through microwave images and AI presents a unique opportunity to enhance the current process and minimize food wastage. Particularly in avocado maturity prediction, microwave imaging provides a non-invasive solution to see through the shell and predict the maturity intelligently. However, conventional deep learning models are generally data-hungry, requiring huge amounts of training data to maintain high performance. In this paper, we propose a few-shot learning (FSL) model to address the need for a large training dataset in maturity estimation. We classify avocado microwave images for maturity assessment through a prototypical FSL model. The FSL model achieves an accuracy range of 80%–96 % across the different experimental groups and all outperforms the conventional deep learning in scenarios where limited data is available for training. This experiment demonstrates the feasibility and accuracy of utilizing microwave scanning and FSL to determine avocado maturity.

The performance of the suspension is a crucial criterion for evaluating both vehicle handling and passenger comfort. To enhance suspension performance, this study proposes the design of a Quantum Genetic Fuzzy Sliding Mode Controller (S-QFSMC) based on the Smith predictor estimator, building upon the foundation of the vehicle magneto-rheological semi-active air suspension. According to the physical model of the vehicle suspension, a mechanical model of a quarter-vehicle magneto-rheological semi-active air suspension with time delay is established. On this basis, a conventional sliding mode controller is designed, and quantum genetic algorithm and fuzzy control principles are employed to optimize the chattering issue associated with sliding mode control. The Smith predictor estimator is utilized to effectively compensate for the time delay in the suspension system. Subsequently, a simulation analysis of the vehicle suspension performance is conducted. The results indicate that, compared to passive suspension control, both the QFSMC controller and the S-QFSMC controller improve the suspension performance, with the S-QFSMC controller exhibiting superior comprehensive improvement. This validates the effectiveness of the designed controllers.

Abstract Background Prostate cancer (PCa) initially shows satisfactory response to therapies targeting the androgen receptor (AR). However, progression to a castration‐resistant stage indicates poor prognosis in PCa patients. AR signalling still plays a central role in most castration‐resistant prostate cancers (CRPC). Therefore, unveiling the mechanisms of AR reactivation under androgen‐deprived conditions is imperative to discover novel therapeutic targets for CRPC. Methods Using an integrative analysis of the transcriptomics of three independent PCa cohorts and a published landscape of AR‐regulated long non‐coding RNA (lncRNA), lncRNA LINC01126 was selected as a candidate gene that could drive CRPC progression for further study. Quantitative reverse transcription polymerase chain reaction, in situ hybridisation (ISH) and fluorescent ISH were performed to detect LINC01126 in PCa tissues and cells. The functional role and mechanism of LINC01126 were further investigated using in vitro and in vivo gain and loss of function assays. Results LINC01126, identified as an AR‐repressed lncRNA, was significantly upregulated after AR‐targeted therapies. In addition, we found that LINC01126 was upregulated in CRPC and was associated with poor prognosis. We also proved that LINC01126 stabilised AR protein and enhanced AR nuclear translocation and transactivation by promoting the transition from O‐GlcNAcylation at threonine 80 to phosphorylation at serine 81 (S81) within the AR protein. Mechanism analysis revealed that LINC01126 facilitates the interaction of CDK9 with AR and impedes the binding of O‐linked N‐acetylglucosamine (O‐GlcNAc) transferase to AR. Consequently, LINC01126 expression was sufficient to activate AR signalling without androgen. LINC01126 overexpression increased, whereas LINC01126 knockdown decreased castration resistance traits in PCa cells in vitro and in vivo. Furthermore, our data showed that LINC01126‐targeting antisense oligonucleotides (ASO) substantially inhibited CRPC cells in vitro. Conclusions Our research expands the functions of AR‐regulated lncRNA in sustaining androgen‐independent AR activity and promoting CRPC progression and reveals that LINC01126 may be a new therapeutic target for PCa.

Benzoxazinoids (BXs) are tryptophan-derived indole metabolites and play a role in various physiological processes, such as auxin metabolism. Auxin is essential in the process of somatic embryogenesis (SE) in plants. In this study, we used bioinformatics, transcriptome data, exogenous treatment experiments, and qPCR analysis to study the evolutionary pattern of Bx genes in green plants, the regulatory mechanism of DlBx genes during early SE, and the effect of 2,4-dihydroxy-7-methoxy-1,4-benzoxazine-3-one (DIMBOA) on the early SE in Dimocarpus longan Lour. The results showed that 27 putative DlBxs were identified in the longan genome; the Bx genes evolved independently in monocots and dicots, and the main way of gene duplication for the DlBx was tandem duplication (TD) and the DlBx were strongly constrained by purification selection during evolution. The transcriptome data indicated varying expression levels of DlBx during longan early SE, and most DlBxs responded to light, temperature, drought stress, and 2,4-dichlorophenoxyacetic acid (2,4-D) treatment; qRT-PCR results showed DlBx1, DlBx6g and DlBx6h were responsive to auxin, and treatment with 0.1mg/L DIMBOA for 9 days significantly upregulated the expression levels of DlBx1, DlBx3g, DlBx6c, DlBx6f, DlB6h, DlBx7d, DlBx8, and DlBx9b. The correlation analysis showed a significantly negative correlation between the expression level of DlBx1 and the endogenous IAA contents; DIMBOA significantly promoted the early SE and significantly changed the endogenous IAA content, and the IAA content increased significantly at the 9th day and decreased significantly at the 13th day. Therefore, the results suggested that DIMBOA indirectly promote the early SE by changing the endogenous IAA content via affecting the expression level of DlBx1 and hydrogen peroxide (H2O2) content in longan.

The treadmill exercise test (TET) serves as a non-invasive method for the diagnosis of coronary artery disease (CAD). Despite its widespread use, TET reports are susceptible to external influences, heightening the risk of misdiagnosis and underdiagnosis. In this paper, we propose a novel automatic CAD diagnosis approach. The proposed approach introduces a customized preprocessing method to obtain clear electrocardiograms (ECGs) from individual TET reports. Additionally, it presents TETDiaNet, a novel neural network designed to explore the temporal relationships within TET ECGs. Central to TETDiaNet is the TETDia block, which mimics clinicians’ diagnostic processes to extract essential diagnostic information. This block encompasses an intra-state contextual learning module and an inter-state contextual learning module, modeling the temporal relationships within a single state and between states, respectively. These two modules help the TETDia block to capture effective diagnosis information by exploring the temporal relationships within TET ECGs. Furthermore, we establish a new TET dataset named TET4CAD for CAD diagnosis. It contains simplified TET reports for 192 CAD patients and 224 non-CAD patients, and each patient undergoes coronary angiography for labeling. Experimental results on TET4CAD underscore the superior performance of the proposed approach, highlighting the discriminative value of the temporal relationships within TET ECGs for CAD diagnosis.

Abstract American football games attract significant worldwide attention every year. Identifying players from videos in each play is also essential for the indexing of player participation. Processing football game video presents great challenges such as crowded settings, distorted objects, and imbalanced data for identifying players, especially jersey numbers. In this work, we propose a deep learning-based player tracking system to automatically track players and index their participation per play in American football games. It is a two-stage network design to highlight areas of interest and identify jersey number information with high accuracy. First, we utilize an object detection network, a detection transformer, to tackle the player detection problem in a crowded context. Second, we identify players using jersey number recognition with a secondary convolutional neural network, then synchronize it with a game clock subsystem. Finally, the system outputs a complete log in a database for play indexing. We demonstrate the effectiveness and reliability of player tracking system by analyzing the qualitative and quantitative results on football videos. The proposed system shows great potential for implementation in and analysis of football broadcast video.

Abstract Proximity labeling was recently developed to detect protein–protein interactions and members of subcellular multiprotein structures in living cells. Proximity labeling is conducted by fusing an engineered enzyme with catalytic activity, such as biotin ligase, to a protein of interest (bait protein) to biotinylate adjacent proteins. The biotinylated protein can be purified by streptavidin beads, and identified by mass spectrometry (MS). TurboID is an engineered biotin ligase with high catalytic efficiency, which is used for proximity labeling. Although TurboID‐based proximity labeling technology has been successfully established in mammals, its application in plant systems is limited. Here, we report the usage of TurboID for proximity labeling of FIP37, a core member of m6A methyltransferase complex, to identify FIP37 interacting proteins in Arabidopsis thaliana. By analyzing the MS data, we found 214 proteins biotinylated by GFP‐TurboID‐FIP37 fusion, including five components of m6A methyltransferase complex that have been previously confirmed. Therefore, the identified proteins may include potential proteins directly involved in the m6A pathway or functionally related to m6A‐coupled mRNA processing due to spatial proximity. Moreover, we demonstrated the feasibility of proximity labeling technology in plant epitranscriptomics study, thereby expanding the application of this technology to more subjects of plant research.

Summary: China’s progress in decarbonizing its transportation, particularly vehicle electrification, is notable. However, the economically effective pathways are underexplored. To find out how much cost is necessary for carbon neutrality for the light-duty vehicle (LDV) sector, this study examines twenty decarbonization pathways, combining the New Energy and Oil Consumption Credit model and the China-Fleet model. We find that the 2060 zero-greenhouse gas (GHG) emission goal for LDVs is achievable via electrification if the battery pack cost is under CNY483/kWh by 2050. However, an extra of CNY8.86 trillion internal subsidies is needed under pessimistic battery cost scenarios (CNY759/kWh in 2050) to eliminate 246 million tonnes of CO2-eq by 2050 ensuring over 80% market penetration of battery electric vehicles (BEVs) in 2050. Moreover, the promotion of fuel cell electric vehicles is synergy with BEVs to mitigate the carbon abatement difficulties, decreasing up to 34% of the maximum marginal abatement internal investment.

Haemophilia B is a rare inherited bleeding disorder in which patients have impaired coagulation. This study describes a patient with Haemophilia B and paroxysmal supraventricular tachycardia (PSVT) who underwent radio frequency catheter ablation (RFCA). The perioperative replacement therapy with coagulation factor IX (FIX) was agreed upon after an interdisciplinary consultation involving a team of specialists in haematology, cardiovascular medicine and cardiothoracic surgery. There were no obvious bleeding points or complications during the perioperative period following the treatment, nor recurrence of PSVT within a three-year follow-up period. In summary, RFCA can be performed safely in patients with haemophilia B on the premise of developing an individualized perioperative exogenous coagulation factor supplementation regimen based upon an adequate preoperative evaluation and clinical monitoring and management by an interdisciplinary team.

Abstract A communication channel should be built to transmit information from one place to another. Imaging is 2 or higher dimensional information communication. Conventionally, an imaging channel comprises a lens with free space at its both sides, whose transfer function is usually known and hence the response of the imaging channel can be well defined. Replacing the lens with a thin scattering medium, the image can still be extracted from the detected optical field, suggesting that the scattering medium retains or reconstructs not only energy but also information transmission channels. Aided by deep learning, we find that unlike the lens system, there are different channels in a scattering medium: the same scattering medium can construct different channels to match the manners of source coding. Moreover, it is found that without a valid channel, the convolution law for a spatial shift-invariant system (the output is the convolution of the point spread function and the input object) is broken, and in this scenario, information cannot be transmitted onto the detection plane. Therefore, valid channels are essential to transmit information through even a spatial shift-invariant system. These findings may intrigue new adventures in imaging through scattering media and reevaluation of the known spatial shift-invariance in various areas.

Abstract The E3 ligase TNF receptor-associated factor 4 (TRAF4) is upregulated and closely associated with tumorigenesis and the progression of multiple human malignancies. However, its effect on radiosensitivity in colorectal cancer (CRC) has not been elucidated. The present study found that TRAF4 was significantly increased in CRC clinical tumor samples. Depletion of TRAF4 impaired the malignant phenotype of CRC cells and sensitized irradiation-induced cell death. Irradiation activated the c-Jun N-terminal kinases (JNKs)/c-Jun signaling via increasing JNKs K63-linked ubiquitination and phosphorylation. Furthermore, c-Jun activation triggered the transcription of the antiapoptotic protein Bcl-xL, thus contributing to the radioresistance of CRC cells. TRAF4 was positively correlated with c-Jun and Bcl-xL, and blocking TRAF4 or inhibiting Bcl-xL with inhibitor markedly promoted ionizing radiation (IR)-induced intrinsic apoptosis and sensitized CRC cells to radiotherapy in vitro and in vivo. Our findings illustrate a potential mechanism of radioresistance, emphasizing the clinical value of targeting the TRAF4/Bcl-xL axis in CRC therapy.

Abstract The E3 ligase TNF receptor-associated factor 4 (TRAF4) is frequently overexpressed and closely related to poor prognosis in human malignancies. However, its effect on carcinogenesis and radiosensitivity in oral squamous cell carcinoma (OSCC) remains unclear. The present study found that TRAF4 was significantly upregulated in primary and relapsed OSCC tumor tissues. Depletion of TRAF4 markedly improved the sensitivity of OSCC cells to irradiation (IR) treatment, showing that tumor cell proliferation, colony formation and xenograft tumor growth were reduced. Mechanistically, IR promoted the interaction between TRAF4 and Akt to induce Akt K63-mediated ubiquitination and activation. TRAF4 knockout inhibited the phosphorylation of Akt and upregulated GSK3β activity, resulting in increased myeloid cell leukemia-1 (MCL-1) S159 phosphorylation, which disrupted the interaction of MCL-1 with Josephin domain containing 1 (JOSD1), and ultimately induced MCL-1 ubiquitination and degradation. Moreover, TRAF4 was positively correlated with MCL-1 in primary and in radiotherapy-treated, relapsed tumor tissues. An MCL-1 inhibitor overcame radioresistance in vitro and in vivo. Altogether, the present findings suggest that TRAF4 confers radioresistance in OSCC by stabilizing MCL-1 through Akt signaling, and that targeting TRAF4 may be a promising therapeutic strategy to overcome radioresistance in OSCC.

Abstract Background Maintaining intraoperative haemodynamic stability can reduce cardiovascular complications during surgery for pheochromocytoma and paraganglioma (PPGL). Risk factors such as tumour size and catecholamine levels are reported to predict haemodynamic responses during surgery for PPGL. We hypothesized that additional factors including body composition and genetic information could further improve prediction. Methods Consecutive patients with PPGL confirmed by surgical pathology between June 2010 and June 2019 were retrospectively included. Cross‐sectional computed tomography images at the L3 level were used to assess body composition parameters including skeletal muscle area and visceral fat area. Next‐generation sequencing was performed using a panel containing susceptibility genes of PPGL. Differences in clinical‐genetic characteristics and body composition parameters were analysed and compared in patients with and without intraoperative haemodynamic instability (HDI). Results We included 221 patients with PPGL (median age 47 [38–56] years, and 52% male). Among them, 49.8% had Cluster 2 mutations (related to kinase signalling pathways), 44.8% had sarcopenia, and 52.9% experienced intraoperative HDI. Compared with patients without HDI, more patients with HDI had Cluster 2 mutations (59.8% vs. 38.5%, P = 0.002) and less had sarcopenia (35.9% vs. 54.8%, P = 0.005). Multivariate analysis showed that urine vanillylmandelic acid ≥ 58 μmol/day (adjusted odds ratio [OR] = 1.840, 95% confidence interval [CI] = 1.012–3.347, P = 0.046), tumour size ≥ 4 cm (adjusted OR = 2.278, 95% CI = 1.242–4.180, P = 0.008), and Cluster 2 mutations (adjusted OR = 2.199, 95% CI = 1.128–4.285, P = 0.021) were independent risk factors for intraoperative HDI, while sarcopenia (adjusted OR = 0.475, 95% CI = 0.266–0.846, P = 0.012) decreased the risk. Conclusions Body composition and genotype were associated with intraoperative haemodynamics in patients with PPGL. Our results indicated that inclusion of body composition and genotype in the overall assessment of patients with PPGL helped to predict HDI during surgery, which could assist in implementing preoperative and intraoperative measures to reduce perioperative complications.

Abstract Overexpression of survivin is frequently observed in human malignancies and is associated with poor prognosis. The present study found that survivin is highly expressed in nasopharyngeal carcinoma (NPC) tumor tissues. Depleting survivin with shRNA inhibited cell viability, colony formation, and in vivo tumorigenesis of NPC cells. With a natural product screening, we identified Butein as a potential anti-tumor compound for NPC by reducing survivin protein level. Butein shortened the half-life of survivin and enhanced ubiquitination-mediated degradation. The mechanism study showed that Butein promoted the interaction between survivin and E3 ligase Fbxl7, and the knockdown of Fbxl7 compromised Butein-induced survivin ubiquitination. Butein suppressed the Akt-Wee1-CDK1 signaling and decreased survivin Thr34 phosphorylation, facilitating E3 ligase Fbxl7-mediated survivin ubiquitination and degradation. Moreover, Butein exhibited a strong in vivo anti-tumor activity, as the tumor volume of Butein-treated xenografts was reduced significantly. Butein alone or combined with cisplatin (CDDP) overcame chemoresistance in NPC xenograft tumors. Overall, our data indicate that Butein is a promising anti-tumor agent for NPC treatment.

Abstract Background Homologous recombination deficiency (HRD) is closely associated with patient prognosis and treatment options in prostate cancer (PCa). However, there is a lack of quantitative indicators related to HRD to predict the prognosis of PCa accurately. Methods We screened HRD-related genes based on the HRD scores and constructed an HRD cluster system to explore different clinicopathological, genomic, and immunogenomic patterns among the clusters. A risk signature, HRDscore, was established and evaluated by multivariate Cox regression analysis. We noticed that SLC26A4, a model gene, demonstrated unique potential to predict prognosis and HRD in PCa. Multi-omics analysis was conducted to explore its role in PCa, and the results were validated by qRT-PCR and immunohistochemistry. Results Three HRD clusters were identified with significant differences in patient prognosis, clinicopathological characteristics, biological pathways, immune infiltration characteristics, and regulation of immunomodulators. Further analyses revealed that the constructed HRDscore system was an independent prognostic factor of PCa patients with good stability. Finally, we identified a single gene, SLC26A4, which significantly correlated with prognosis in three independent cohorts. Importantly, SLC26A4 was confirmed to distinguish PCa (AUC for mRNA 0.845; AUC for immunohistochemistry score 0.769) and HRD (AUC for mRNA 0.911; AUC for immunohistochemistry score 0.689) at both RNA and protein levels in our cohort. Conclusion This study introduces HRDscore to quantify the HRD pattern of individual PCa patients. Meanwhile, SLC26A4 is a novel biomarker and can reasonably predict the prognosis and HRD in PCa.

The eukaryotic ribosome is essential for cancer cell survival. Perturbation of ribosome biogenesis induces nucleolar stress or ribosomal stress, which restrains cancer growth, as rapidly proliferating cancer cells need more active ribosome biogenesis. In this study, we found that UTP11 plays an important role in the biosynthesis of 18S ribosomal RNAs (rRNA) by binding to the pre-rRNA processing factor, MPP10. UTP11 is overexpressed in human cancers and associated with poor prognoses. Interestingly, depletion of UTP11 inhibits cancer cell growth in vitro and in vivo through p53-depedednt and -independent mechanisms, whereas UTP11 overexpression promotes cancer cell growth and progression. On the one hand, the ablation of UTP11 impedes 18S rRNA biosynthesis to trigger nucleolar stress, thereby preventing MDM2-mediated p53 ubiquitination and degradation through ribosomal proteins, RPL5 and RPL11. On the other hand, UTP11 deficiency represses the expression of SLC7A11 by promoting the decay of NRF2 mRNA, resulting in reduced levels of glutathione (GSH) and enhanced ferroptosis. Altogether, our study uncovers a critical role for UTP11 in maintaining cancer cell survival and growth, as depleting UTP11 leads to p53-dependent cancer cell growth arrest and p53-independent ferroptosis.

Abstract Despite advancements made in the therapeutic strategies on hepatocellular carcinoma (HCC), the survival rate of HCC patient is not satisfactory enough. Therefore, there is an urgent need for the valuable prognostic biomarkers in HCC therapy. In this study, we aimed to screen hub genes correlated with prognosis of HCC via multiple databases. 117 HCC-related genes were obtained from the intersection of the four databases. We subsequently identify 10 hub genes (JUN, IL10, CD34, MTOR, PTGS2, PTPRC, SELE, CSF1, APOB, MUC1) from PPI network by Cytoscape software analysis. Significant differential expression of hub genes between HCC tissues and adjacent tissues were observed in UALCAN, HCCDB and HPA databases. These hub genes were significantly associated with immune cell infiltrations and immune checkpoints. The hub genes were correlated with clinical parameters and survival probability of HCC patients. 147 potential targeted therapeutic drugs for HCC were identified through the DGIdb database. These hub genes could be used as novel prognostic biomarkers for HCC therapy.

BackgroundNear-infrared fluorescence (NIRF) imaging has recently emerged as a promising tool for noninvasive cancer imaging. However, lack of tumor sensitivity and specificity restricts the application of NIRF dyes in surgical navigation.MethodsHerein, we investigated the imaging features of NIRF dye MHI-148 and indocyanine green (ICG) in live cell imaging and xenograft nude mice models. TCGA dataset analysis and immunohistochemistry were conducted to investigate the expression of OATPs or ABCGs in hepatocellular carcinoma (HCC) tissues. OATPs or ABCGs were knocked down and overexpressed in HCC cells using transient transfection by siRNA and plasmids or stable transfection by lentivirus. Further, qRT-PCR ,Western blotting and the use of agonists or inhibitors targeting β-catenin signaling pathway were applied to explore its important role in regulation of OATP2B1 and ABCG2 expression.ResultsHere we demonstrated that NIRF dye MHI-148 was biocompatible as indocyanine green (ICG) but with higher imaging intensity and preferential uptake and retention in hepatocellular carcinoma (HCC) cells and tissues. Moreover, our data indicated that membrane transporters OATP2B1 and ABCG2, which regulated by β-catenin signaling pathway, mediated tumor-specific accumulation and retention of MHI-148 in HCC cells. In addition, the treatment with β-catenin inhibitor significantly enhanced the accumulation of MHI-148 in HCC tissues and improved the efficacy of tumor imaging with MHI-148 in vivo.ConclusionsOur study uncovers a mechanism that links the distribution and expression of the membrane transporters OATP2B1 and ABCG2 to the tumor-specific accumulation of MHI-148, and provides evidence supporting a regulating role of the β-catenin signaling pathway in OATP2B1 and ABCG2- induced retention of MHI-148 inHCC tissues, and strategy targeting key components of MHI-148 transport machinery may be a potential approach to improve HCC imaging.

BackgroundDespite the recent progress of therapeutic strategies in treating prostate cancer (PCa), the majority of patients still eventually relapse, experiencing dismal outcomes. Therefore, it is of utmost importance to identify novel viable targets to increase the effectiveness of treatment. The present study aimed to investigate the potential relationship between N6-methyladenosine (m6A) RNA modification and PCa development and determine its clinical relevance.MethodsThrough systematic analysis of the TCGA database and other datasets, we analyzed the gene expression correlation and mutation profiles of m6A-related genes between PCa and normal tissues. Patient samples were divided into high- and low-risk groups based on the results of Least Absolute Shrinkage and Selection Operator (LASSO) Cox analysis. Subsequently, differences in biological processes and genomic characteristics of the two risk groups were determined, followed by functional enrichment analysis and gene set enrichment (GSEA) analysis. Next, we constructed the protein-protein interaction (PPI) network of differentially expressed genes between patients in high- and low-risk groups, along with the mRNA-miRNA-lncRNA network. The correlation analysis of tumor-infiltrating immune cells was further conducted to reveal the differences in immune characteristics between the two groups.ResultsA variety of m6A-related genes were identified to be differentially expressed in PCa tissues as compared with normal tissues. In addition, the PPI network contained 278 interaction relationships and 34 m6A-related genes, and the mRNA-miRNA-lncRNA network contained 17 relationships, including 91 miRNAs. Finally, the immune characteristics analysis showed that compared with the low-risk group, the levels of M1 and M2 macrophages in the high-risk group significantly increased, while the levels of mast cells resting and T cells CD4 memory resting significantly decreased.ConclusionsThis study provides novel findings that can further the understanding of the role of m6A methylation during the progression of PCa, which may facilitate the invention of targeted therapeutic drugs.

BackgroundThis study used bibliometrics to define and analyze the characteristics of the first 100 most cited papers on the topic of neuroendocrine prostate cancer (NEPC).MethodsWe explored the Web of Science Core Collection database, and screened the top 100 most frequently cited articles and reviews with the title NEPC or small cell prostate cancer (SCPC). We conducted bibliometrics research on the screening results to identify the most influential journals and authors in the field of NEPC.ResultsThe first 100 most cited papers have been cited a total of 14,795 times, from 73 to 833 times (mean ± standard deviation, 147.95 ± 101.68). All top 100 most cited papers were published from 1984 to 2019, and the total number of citations for papers published in 2016 was significantly higher than that for papers published in other years. The journal with the largest number of published papers is “Prostate” (n=8). “Neuroendocrine differentiation” has become the most frequently used author keyword. “Oncology” is the most popular topic in the field of NEPC.ConclusionWe analyzed the first 100 most cited papers in the NEPC field by collecting detailed information, which provide guiding opinions for finding the most influential journals and authors in NEPC-related fields. We hope to help researchers and readers in this field improve their understanding of NEPC research trends and provide ideas for future research from a unique perspective.

Herein, we report two cases of successful application of indocyanine green (ICG) fluorescence imaging for detecting intraoperative bile leakage during laparoscopic cholecystectomy (LC). Bile leakage was detected rapidly and accurately using fluorescence guidance. Based on our findings, we recommend using ICG fluorescence imaging during LC because it is effective and feasible for detecting intraoperative bile leakage.

Autophagy pathway involves maintaining intracellular homeostasis by regulating the degradation of cytoplasmic components. Disfunction of autophagic process has been confirmed to be critical mechanism in many diseases, including cancer, inflammation, infection, degeneration and metabolic disorders. Recent studies have shown that autophagy is one of the early events in acute pancreatitis. Impaired autophagy promotes the abnormal activation of zymogen granules and results in apoptosis and necrosis of exocrine pancreas. Furthermore, multiple signal paths involve progression of acute pancreatitis by regulating autophagy pathway. This article provides a comprehensive review of the recent advances in epigenetic regulation of autophagy and the role of autophagy in acute pancreatitis.

Cancer is a major medical problem worldwide. Due to its high heterogeneity, the use of the same drugs or surgical methods in patients with the same tumor may have different curative effects, leading to the need for more accurate treatment methods for tumors and personalized treatments for patients. The precise treatment of tumors is essential, which renders obtaining an in-depth understanding of the changes that tumors undergo urgent, including changes in their genes, proteins and cancer cell phenotypes, in order to develop targeted treatment strategies for patients. Artificial intelligence (AI) based on big data can extract the hidden patterns, important information, and corresponding knowledge behind the enormous amount of data. For example, the ML and deep learning of subsets of AI can be used to mine the deep-level information in genomics, transcriptomics, proteomics, radiomics, digital pathological images, and other data, which can make clinicians synthetically and comprehensively understand tumors. In addition, AI can find new biomarkers from data to assist tumor screening, detection, diagnosis, treatment and prognosis prediction, so as to providing the best treatment for individual patients and improving their clinical outcomes.

Microwave imaging technology is a useful method often applied in medical diagnosis and can be used by the food industry to ensure food safety and quality. For fruit, ripeness is the primary characteristic which determines quality for the consumer. This paper proposes a novel microwave imaging system to determine the ripeness of watermelon as a proof of concept. The design employs a circular array with 10 Coplanar Vivaldi antennas offering wide bandwidth, high gain, and high efficiency. S-parameters between antennas are collected quickly via automated channel switching for fast image generation. Eight different watermelon samples of varying ripeness, type, dimensions, and origin are scanned and imaged. Comparisons with sample cross-sections show distinct differences in image characteristics based on watermelon maturity. Sugar concentration of unripe and ripe watermelon is also measured and plotted for further validation of the imaging technique.

The Sarakan Gold Deposit is located in the vicinity of the Songsanu and Napafa villages, north of Sarakan County, Vientiane Province, Laos. It forms part of the Luang Prabang–Loei polymetallic metallogenic belt, and its metallogenic geological conditions are good and mineral resources are abundant. At present, most orebodies (mineralization) are deeply buried and greatly vary in terms of their characteristics; furthermore, the distribution and output of orebodies (mineralization) are not clear, which makes it difficult to find minerals in the area. Based on the comprehensive geological characteristics, geophysical anomalies, and interpretation results in the study area, it is believed that the Sarakan Gold Deposit is closely related to Indosinian felsic substance magmatic intrusions and is controlled by their structure. The type of deposits in the belt are brittle–ductile, shear structured, Quartz-pyrite, vein-type gold deposits. In this study, we carried out comprehensive geophysical methods, including the high-precision magnetic survey, induced polarization survey, and the transient electromagnetic measurement. Based on the characteristics of geophysical anomalies, geological inference, and interpretation, the integrated geophysical and geochemical prospecting criteria of the ore area have been determined: high magnetism, high polarization, and medium–high resistance are the signs pointing to concealed mineralization bodies in the study area, and this provided the best framework for us to discuss the deep geological bodies in the study area. The drilling verification results are consistent with the abnormalities delineated by the magnetic and electrical measurements. Our geophysical exploration results revealed the coupling relationship between the concealed intrusive body of the Sarakan Gold Deposit and the metallogenic structure, which provided a great opportunity for finding potentially similar deposits in the Luang Prabang–Loei polymetallic metallogenic belt.

Objective Here, we aimed to compare early hepatectomy (EH) with delayed hepatectomy (DH) as a treatment for spontaneously ruptured hepatocellular carcinoma (HCC). Methods Several databases were systematically searched for eligible studies that compared DH with EH for spontaneously ruptured HCC treatment. Studies that met the inclusion criteria were reviewed systematically, and the reported data were aggregated statistically, using the RevMan v5.3 software. Results Seven studies were included, with a total of 385 patients, comprising of 224 EH cases and 161 DH cases. Compared with the EH group, incidence of intraoperative bleeding [mean difference (MD), 353.93; 95% CI, 230.04-447.83; P < 0.00001], volume of intraoperative blood transfusion (MD, 420.61; 95% CI, 354.40-486.81, P < 0.00001), and 30-day mortality rate (OR, 14.94; 95% CI, 1.76-126.66; P = 0.01) were significantly lower in the DH group. Furthermore, the 1-, 2-, and 3-year survival rates were significantly higher in the DH group [1-year：hazard ratio (HR), 1.76; 95% CI, 1.06-2.94; P = 0.03; 2-year：HR, 1.52; 95% CI, 1.02-2.25; P = 0.04; 3-year: HR, 1.53; 95% CI, 1.06-2.21; P = 0.02]. There was no difference between the groups in the 5-year survival rate (HR, 1.40; 95% CI, 0.92-2.11; P = 0.11). Conclusion For resectable spontaneously ruptured HCC, DH could reduce intraoperative bleeding, intraoperative blood transfusion volume, and 30-day mortality rate and increase the 1-, 2-, and 3-year survival rates, endowing the patients with greater short- and long-term benefits during and following the surgery.

Abstract Background Children with acute lymphoblastic leukemia (ALL) undergoing chemotherapy experience a relatively high risk of infection. And the disturbance of gut microbiota is generally believed to impair intestinal barrier function and may induce bacterial infections and inflammation. The study aimed to investigate the alterations in the gut microbiota and assess its relationship with chemotherapy-induced pneumonia in pediatric ALL patients. Methods We conducted a case–control study with 14 cases affected by pneumonia and 44 unaffected subjects and characterized the physiological parameters and gut microbiota by microarray-based technique. Results There were significant differences in α- and β-diversity in the affected group compared with the control group. At species level, the LEfSe analysis revealed that Enterococcus malodoratus, Ochrobactrum anthropi and Actinomyces cardiffensis were significantly abundant in the affected subjects. A receiver operating characteristic (ROC) curve yielded the area under the curve (AUC) of 0.773 for classification between the two groups. In addition, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways involved in the bacterial secretion system were more enriched in the affected group than in the control group. Conclusions Gut microbiota alteration was associated with chemotherapy-induced pneumonia in pediatric ALL patients, which provided a new perspective on the personalized clinical care of pediatric ALL.

Abstract Layered IV-V-VI semiconductors have immense potential for thermoelectric (TE) applications due to their intrinsically ultralow lattice thermal conductivity. However, it is extremely difficult to assess their TE performance via experimental trial-and-error methods. Here, we present a machine-learning-based approach to accelerate the discovery of promising thermoelectric candidates in this chalcogenide family. Based on a dataset generated from high-throughput ab initio calculations, we develop two highly accurate-and-efficient neural network models to predict the maximum ZT (ZT max) and corresponding doping type, respectively. The top candidate, n-type Pb2Sb2S5, is successfully identified, with the ZT max over 1.0 at 650 K, owing to its ultralow thermal conductivity and decent power factor. Besides, we find that n-type Te-based compounds exhibit a combination of high Seebeck coefficient and electrical conductivity, thereby leading to better TE performance under electron doping than hole doping. Whereas p-type TE performance of Se-based semiconductors is superior to n-type, resulting from large Seebeck coefficient induced by high density-of-states near valence band edges.

Cholangiocarcinoma (CCA) is a rare disease with poor prognosis, and surgery remains the only curative treatment option. However, surgery is inappropriate for the majority of patients with CCA. Conversion therapy may provide opportunities for the surgical treatment of these patients. Herein, we describe a patient with intrahepatic CCA who was first treated with albumin-bound paclitaxel, cisplatin, and gemcitabine in combination with camrelizumab. The patient then successfully underwent surgery and achieved pathological complete remission. This report can serve as a reference for clinicians regarding conversion therapy for intrahepatic CCA.

The rubber expansion in Asian countries has led to various environmental problems. To smoothly promote the ecological restoration programs, an essential premise is that the local government must consider public attitude and understand the public willingness to pay (WTP) for the programs. In this study, we employ an integrated contingent valuation (ICV) survey to evaluate the citizen’s WTP of implementing rubber plantation ecological restoration (RPER) programs in Hainan, China. Considering three types of the respondents’ WTP data (interval truncated, merged, and point data), we adopt the Point and Interval Data (PID) model to estimate the determinants of WTP and calculate the non-market value with the comparison of the Tobit model. Results show that the mean value of WTP for the RPER program is 178 yuan per year, and the total non-market value throughout the province is worth approximately 1.839 billion yuan per year after controlling the regional differences. We also find that the respondents’ WTP has a significant regional difference, in which Danzhou has the highest WTP, followed by Haikou, Wanning, and Sanya. Age has a significant negative effect on the WTP for the restoration program, whereas the factors such as education, family burden, income, and residents’ environmental knowledge have a significant positive effect. Our findings add to the evidence that using improved estimation methods can generate diverse results, where neglecting the bias caused by the usual interval data model would lead to downward biased estimates.

Background: Ischemic stroke is a leading cause of mortality and disability worldwide. Microcirculatory dysfunction is the foremost hindrance for a good clinical prognosis in ischemic stroke patients. Clinical researches show that Chuanzhitongluo capsule (CZTL) has a curative effect during the recovery period of ischemic stroke, which contributes to a good prognosis. However, it is not known whether CZTL treats ischemic stroke by ameliorating microcirculation dysfunction.Objective: In this study, we investigated the influence of CZTL on microcirculation and its underlying mechanism.Methods: A rat model of acute microcirculatory dysfunction was established by stimuli of adrenaline and ice water. The microcirculatory damage in model rats and the efficacy of CZTL were assessed by detecting laser speckle contrast imaging, coagulation function, hemorheology, vasomotor factor and microcirculation function. The potential mechanism of CZTL action was explored by the untargeted metabolomic analysis based on ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry.Results: Laser speckle contrast imaging showed that model rats suffered low perfusion in ears, feet and tails, and CZTL treatment increased microcirculatory blood flow. Coagulation function detection results showed that CZTL diminished the reduction of thrombin time, prothrombin time, activated partial thromboplastin time and the elevated fibrinogen level caused by acute microcirculatory dysfunction. Furthermore, CZTL could recover the increased blood viscosity as well as the abnormal vasomotor and microcirculation function in rats with acute microcirculatory dysfunction. Metabolomics analysis indicated that CZTL might regulate sphingolipid metabolism and arachidonic acid metabolism to exert protective effects on microcirculation.Conclusion: These results elucidated that CZTL was highly effective against microcirculatory dysfunction and its potential mechanisms related with the modulation of sphingolipid and arachidonic acid metabolic pathways. The present study provided a new perspective on the clinical application of CZTL, and it contribute to explore novel therapeutic drug against microcirculatory dysfunction.

Abstract Renal fibrosis is a common pathological process that occurs with diverse etiologies in chronic kidney disease. However, its regulatory mechanisms have not yet been fully elucidated. Ferroptosis is a form of non-apoptotic regulated cell death driven by iron-dependent lipid peroxidation. It is currently unknown whether ferroptosis is initiated during unilateral ureteral obstruction (UUO)-induced renal fibrosis and its role has not been determined. In this study, we demonstrated that ureteral obstruction induced ferroptosis in renal tubular epithelial cells (TECs) in vivo. The ferroptosis inhibitor liproxstatin-1 (Lip-1) reduced iron deposition, cell death, lipid peroxidation, and inhibited the downregulation of GPX4 expression induced by UUO, ultimately inhibiting ferroptosis in TECs. We found that Lip-1 significantly attenuated UUO-induced morphological and pathological changes and collagen deposition of renal fibrosis in mice. In addition, Lip-1 attenuated the expression of profibrotic factors in the UUO model. In vitro, we used RSL3 treatment and knocked down of GPX4 level by RNAi in HK2 cells to induce ferroptosis. Our results indicated HK2 cells secreted various profibrotic factors during ferroptosis. Lip-1 was able to inhibit ferroptosis and thereby inhibit the secretion of the profibrotic factors during the process. Incubation of kidney fibroblasts with culture medium from RSL3-induced HK2 cells promoted fibroblast proliferation and activation, whereas Lip-1 impeded the profibrotic effects. Our study found that Lip-1 may relieve renal fibrosis by inhibiting ferroptosis in TECs. Mechanistically, Lip-1 could reduce the activation of surrounding fibroblasts by inhibiting the paracrine of profibrotic factors in HK2 cells. Lip-1 may potentially be used as a therapeutic approach for the treatment of UUO-induced renal fibrosis.

ObjectiveTo evaluate whether depression is the contraindication of anterior cervical decompression and fusion (ACDF) for cervical spondylosis.Material and methodsPatients with single-segment cervical spondylosis who underwent ACDF from January 2015 to December 2018 in our department were retrospectively included in this study and divided into two groups. Patients who were diagnosed of depression and prescribed with antidepressant drugs for at least 6 months before surgery were included in the intervention group. Patients without depression were included in the control group. The Beck Depression Inventory (BDI) score was used to evaluate the severity of depression. Visual Analogue Scale (VAS) score, Japanese Orthopeadic Association (JOA) score, Neck Disability Index (NDI), and the 36-Item Short-Form Health Survey (SF-36) were recorded as indexes to assess the pain, cervical spine function, degree of cervical spine injury, and life quality, respectively. The operative time, operative blood loss, hospital stay and complications were also recorded and compared.ResultsA total of 117 patients were included in this study, involving 32 patients in the intervention group and 85 patients in the control group. No significant differences were found in operative time, operative blood loss, hospital stay and complications between the two groups (P>0.05). The BDI score, VAS score, JOA score, NDI, SF-36 physical component score (SF-36 PCS) and SF-36 mental component score (SF-36 MCS) were all significantly improved at last follow-up in both the two groups. The intervention group showed higher BDI score and SF-36 MCS than the control group at both preoperative and the last follow-up (P0.05).ConclusionsDepression is not the contraindication of ACDF for cervical spondylosis. Depression patients who received preoperative antidepressants can achieve similar improvement of clinical symptoms from ACDF with non-depression patients.

Castration-resistant prostate cancer (CRPC) is a therapy-resistant and lethal form of prostate cancer as well as a therapeutic challenge. Prostate-specific membrane antigen (PSMA) has been proved as a promising molecular target for optimizing the theranostics for CRPC patients. When combined with PSMA radiotracers, novel molecular imaging techniques such as positron emission tomography (PET) can provide more accurate and expedient identification of metastases when compared with conventional imaging techniques. Based on the PSMA-based PET scans, the accurate visualization of local and disseminative lesions may help in metastasis-directed therapy. Moreover, the combination of 68Ga-labeled PSMA-based PET imaging and radiotherapy using PSMA radioligand therapy (RLT) becomes a novel treatment option for CRPC patients. The existing studies have demonstrated this therapeutic strategy as an effective and well-tolerated therapy among CRPC patients. PSMA-based PET imaging can accurately detect CRPC lesions and describe their molecular features with quantitative parameters, which can be used to select the best choice of treatments, monitor the response, and predict the outcome of RLT. This review discussed the current and potential role of PSMA‐based imaging and RLT in the diagnosis, treatment, and prediction of prognosis of CRPC.

The tumor microenvironment (TME) is a microecology consisting of tumor and mesenchymal cells and extracellular matrices. The TME plays important regulatory roles in tumor proliferation, invasion, metastasis, and differentiation. Neuroendocrine differentiation (NED) is a mechanism by which castration resistance develops in advanced prostate cancer (PCa). NED is induced after androgen deprivation therapy and neuroendocrine prostate cancer (NEPC) is established finally. NEPC has poor prognosis and short overall survival and is a major cause of death in patients with PCa. Both the cellular and non-cellular components of the TME regulate and induce NEPC formation through various pathways. Insights into the roles of the TME in NEPC evolution, growth, and progression have increased over the past few years. These novel insights will help refine the NEPC formation model and lay the foundation for the discovery of new NEPC therapies targeting the TME.

Adakites are magmatic rocks with specific geochemical characteristics and specific dynamics that provide important clues to understanding the magmatic-tectonic evolution of orogenic belts. We studied the Early Triassic Nanpo adakitic pluton of the Luang Prabang-Loei tectonic belt in the Eastern Tethys domain (Laos Sarakan) using detailed petrological, zircon U-Pb chronological, whole-rock geochemical, and zircon Lu-Hf isotope studies to constrain their petrogenesis. The rocks are predominantly diorites and granodiorites with Early Triassic zircon U-Pb emplacement ages ranging from 247.9 ± 1.0 to 249.0 ± 2.4 Ma. Moderate SiO2 (56.26–65.95 wt%) and Na2O (3.24–5.00 wt%) contents, with Na2O/K2O values between 1.76 and 2.51 and A/CNK values between 0.81 and 0.94, indicate that the rocks belong to the metaluminous calc-alkaline rock series. The high Sr content (590–918 ppm), low Y (6.30–11.89 ppm) and Yb (1.99–3.44 ppm) contents, intermediate Mg# (42–50) values, and high Sr/Y and (La/Yb) N ratios (Sr/Y = 24–41, (La/Yb) N = 6.84–13.8) are typical for adakites. Zircon Hf isotope analysis shows a significant variation in the εHf(t) values (6.7–12.0), with a mean value of 9.4 and a TDM2 of 512–845 Ma. Geochemical evidence indicates that the Nanpo adakitic rock was formed by the partial melting of the thickened lower crust in the plate-breaking environment and has an important contribution to the underplated mantle-derived magma. We propose that the Early Triassic adakites in the Luang Prabang-Loei tectonic belt formed during the transition from subduction to a continental collision, and the mixing of crust- and mantle-derived magmas is the main mechanism for the growth of continental crust in the Paleo-Tethys orogenic belt of southeastern Asia.

The construction of Ecological Civilization has been one of China’s major strategies.Ecological development is the basic industry related to people’s livelihood and the fundamental requirement of high-quality development of China’s Catering Industry under the new development pattern of “Dual Circulation”as a happiness industry in national economy.This paper analyses the necessity and urgency of ecological development of China’s Catering Industry following the theory of Industrial Symbiosis, and summarizes the ecological development path through ecological industrial structure, ecological enterprise operation, ecological industrial culture, ecological technology and ecological competitiveness.Therefore, in the view of advancing the ecological development of China’s Catering Industry, this paper puts forward the following five strategies,enhancing dynamic monitoring of industrial resource consumption and environment protection, strengthening the subjective status of industrial enterprises, perfecting the market mechanism, improving the technology content and the environmental benefits, as well as deepening supply-side structural reform.

The sharing economy has the characteristics of resource-saving and environment-friendly, which is consistent with the goal of reducing food waste, and the cooperative consumption brought by sharing also is in line with the principles of food surplus redistribution and food waste management.In the current practice of reducing food waste in China, the sharing economy model, which is mature in other fields, has less penetration into the food sector, although the overseas food sharing models had become very popular, which definitely exerts a positive effect in reducing food wastage.Therefore, focusing on reducing food sharing practices, the paper combed foreign literature research for the relationship between reducing food waste and sharing practices，the food sharing models and the innovative ideas on reducing food waste in the era of digital economy.On this basis, it also proposed that it is necessary to investigate how to apply the sharing model of platform economy to the food waste management in China and put more intensive energy on the research topics on sharing participants, sharing fields, sharing platform and sharing policy.