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Cells apoptosis induced by intense heat stress is the prominent feature of heat-related illness. However, little is known about the biological effects of heat stress on cells apoptosis. Herein, we presented evidence that intense heat stress could induce early apoptosis of HUVEC cells through activating mitochondrial pathway with changes in mitochondrial membrane potential(ΔΨm), release of cytochrome c, and activation of caspase-9 and -3. We further revealed that p53 played a crucial role in heat stress-induced early apoptosis, with p53 protein rapidly translocated into mitochondria. Using pifithrin-α(PFT), a p53's mitochondrial translocation inhibitor, we found that pretreated with PFT, heat stress induced mitochondrial p53 translocation was significantly suppressed, accompanied by a significant alleviation in the loss of ΔΨm, cytochrome c release and caspase-9 activation. Furthermore, we also found that generation of reactive oxygen species (ROS) was a critical mediator in heat stress-induced apoptosis. In addition, the antioxidant MnTMPyP significantly decreased the heat stress-induced p53's mitochondrial translocation, followed by the loss of ΔΨm, cytochrome c release, caspase-9 activation and heat stress-mediated apoptosis. Conclusively, these findings indicate the contribution of the transcription-independent mitochondrial p53 pathway to early apoptosis in HUVEC cells induced by oxidative stress in response to intense heat stress. [ABSTRACT FROM AUTHOR]

Abstract Sarcopenia is the age-related loss of skeletal muscle mass and function. Computed tomography (CT) assessments of sarcopenia utilize measurements of skeletal muscle cross-sectional area (SMA), radiation attenuation (SMRA), and intramuscular adipose tissue (IMAT). Unadjusted SMA is strongly correlated with both height and body mass index (BMI); therefore, SMA must be adjusted for body size to assess sarcopenic low muscle mass fairly in individuals of different heights and BMI. SMA/height (rather than $$SMA/height^2$$ S M A / h e i g h t 2 ) provides optimal height adjustment, and vertebra-specific relative muscle index (RMI) equations optimally adjust for both height and BMI. Since L3 measurement is not available in all CT scans, sarcopenic low muscle mass may be assessed using other levels. Both a mid-vertebral slice and an inferior slice have been used to define ‘L3 SMA’, but the effect of vertebral slice location on SMA measurements is unexplored. Healthy reference values for skeletal muscle measures at mid- and inferior vertebra slices between T10 and L5, have not yet been reported. We extracted T10 through L5 SMA, SMRA, and IMAT at a mid-vertebral and inferior slice using non-contrast-enhanced CT scans from healthy, adult kidney donor candidates between age 18 and 73. We compared paired differences in SMA between the mid-vertebral slice versus the inferior slice. We calculated the skeletal muscle gauge as $$SMG_{HT}=SMRA*SMI_{HT}$$ S M G HT = S M R A ∗ S M I HT . We used allometric analysis to find the optimal height scaling power for SMA. To enable comparisons with other published reference cohorts, we computed two height-adjusted measures; $$SMI_{HT}=SMA/height$$ S M I HT = S M A / h e i g h t (optimal) and $$SMI_{HT2}=SMA/height^2$$ S M I H T 2 = S M A / h e i g h t 2 (traditional). Using the young, healthy reference cohort, we utilized multiple linear regression to calculate relative muscle index z-scores ( $$RMI_{HT}$$ R M I HT , $$RMI_{HT2}$$ R M I H T 2 ), which adjust for both height and BMI, at each vertebra level. We assessed Pearson correlations of each muscle area measure versus age, height, weight, and BMI separately by sex and vertebra number. We assessed the differences in means between age 18–40 versus 20–40 as the healthy, young adult reference group. We reported means, standard deviations, and sarcopenia cutpoints (mean-2SD and 5th percentile) by sex and age group for all measures. Sex-specific allometric analysis showed that height to the power of one was the optimal adjustment for SMA in both men and women at all vertebra levels. Differences between mid-vertebra and inferior slice SMA were statistically significant at each vertebra level, except for T10 in men. $$SMI_{HT}$$ S M I HT was uncorrelated with height, whereas $$SMI_{HT2}$$ S M I H T 2 was negatively correlated with height at all vertebra levels. Both $$SMI_{HT}$$ S M I HT and $$SMI_{HT2}$$ S M I H T 2 were positively correlated with BMI at all vertebra levels. $$RMI_{HT}$$ R M I HT was uncorrelated with BMI, weight, and height (minimal positive correlation in women at $$\hbox {L3}_{inf}$$ L3 inf , $$\hbox {L4}_{mid}$$ L4 mid , and $$\hbox {L5}_{inf}$$ L5 inf ) whereas $$RMI_{HT2}$$ R M I H T 2 was uncorrelated with BMI, but negatively correlated with height and weight at all levels. There were no significant differences in SMA between 18–40 versus 20–40 age groups. Healthy reference values and sarcopenic cutpoints are reported stratified by sex, vertebra level, and age group for each measure. Height to the power of one (SMA/height) is the optimal height adjustment factor for SMA at all levels between $$\hbox {T10}_{mid}$$ T10 mid through $$\hbox {L5}_{inf}$$ L5 inf . The use of $$SMA/height^2$$ S M A / h e i g h t 2 should be discontinued as it retains a significant negative correlation with height and is therefore biased towards identifying sarcopenia in taller individuals. Measurement of SMA at a mid-vertebral slice is significantly different from measurement of SMA at an inferior aspect slice. Reference values should be used for the appropriate slice. We report sarcopenic healthy reference values for skeletal muscle measures at the mid-vertebral and inferior aspect slice for T10 through L5 vertebra levels. Relative muscle index (RMI) equations developed here minimize correlation with both height and BMI, producing unbiased assessments of relative muscle mass across the full range of body sizes. We recommend the use of these RMI equations in other cohorts.

Abstract Evidence supporting aortic calcification as a leverageable cardiovascular risk factor is rapidly growing. Given aortic calcification’s potential as a clinical correlate, we assessed granular vertebral-indexed calcification measurements of the abdominal aorta in a well curated reference population. We evaluated the relationship of aortic calcification measurements with Framingham risk scores. After exclusion, 4073 participants from the Reference Analytic Morphomic Population with varying vertebral levels were included. The percent of the aortic wall calcified was used to assess calcification burden at the L1–L4 levels. Descriptive statistics of participants, sex-specific vertebral indexed calcification measurements, relational plots, and relevant associations are reported. Mean aortic attenuation was higher in female than male participants. Overall, mean aortic calcium was higher with reference to inferior abdominal aortic measurements and demonstrated significant differences across all abdominal levels [L3 Area (mm $$^2$$ 2 ): Females 6.34 (sd 16.60), Males 6.23 (sd 17.21); L3 Volume (mm $$^3$$ 3 ): Females 178.90 (sd 474.19), Males 195.80 (sd 547.36); Wall Calcification (%): Females (L4) 6.97 (sd 16.03), Males (L3) 5.46 (13.80)]. Participants with elevated calcification had significantly higher Framingham risk scores compared to participants with normal calcification scores. Opportunistically measuring aortic calcification may inform further cardiovascular risk assessment and enhance cardiovascular event surveillance efforts.

Abstract Measurements of skeletal muscle cross-sectional area, index, and radiation attenuation utilizing clinical computed tomography (CT) scans are used in assessments of sarcopenia, the loss of skeletal muscle mass and function associated with aging. To classify individuals as sarcopenic, sex-specific cutoffs for ‘low’ values are used. Conventionally, cutoffs for skeletal muscle measurements at the level of the third lumbar (L3) vertebra are used, however L3 is not included in several clinical CT protocols. Non-contrast-enhanced CT scans from healthy kidney donor candidates (age 18–40) at Michigan Medicine were utilized. Skeletal muscle area (SMA), index (SMI), and mean attenuation (SMRA) were measured at each vertebral level between the tenth thoracic (T10) and the fifth lumbar (L5) vertebra. Sex-specific means, standard deviations (s.d.), and sarcopenia cutoffs (mean-2 s.d.) at each vertebral level were computed. Associations between vertebral levels were assessed using Pearson correlations and Tukey’s difference test. Classification agreement between different vertebral level cutoffs was assessed using overall accuracy, specificity, and sensitivity. SMA, SMI, and SMRA L3 cutoffs for sarcopenia were 92.2 cm2, 34.4 cm2/m2, and 34.3 HU in females, and 144.3 cm2, 45.4 cm2/m2, and 38.5 HU in males, consistent with previously reported cutoffs. Correlations between all level pairs were statistically significant and high, ranging from 0.65 to 0.95 (SMA), 0.64 to 0.95 (SMI), and 0.63 to 0.95 (SMRA). SMA peaks at L3, supporting its use as the primary site for CT sarcopenia measurements. However, when L3 is not available alternative levels (in order of preference) are L2, L4, L5, L1, T12, T11, and T10. Healthy reference values reported here enable sarcopenia assessment and sex-specific standardization of SMA, SMI, and SMRA in clinical populations, including those whose CT protocols do not include L3.

The objective of this study was to explore the potential of machine-learning techniques in the automatic identification and classification of brain metastases from a radiomic perspective, aiming to improve the accuracy of tumor volume assessment for radiotherapy. By using various machine-learning algorithms, including random forest, support vector machine, gradient boosting machine, XGBoost, decision tree, artificial neural network, k-nearest neighbors, LightGBM, and CatBoost algorithms, a stacking ensemble model was developed to classify gross tumor volume (GTV), brainstem, and normal brain tissue based on radiomic features. Multiple evaluation metrics, including the specificity, sensitivity, negative predictive value, positive predictive value, accuracy, Matthews correlation coefficient, and the Youden index, were used to assess the model's performance. The stacked ensemble model integrated the strengths of the nine base models and consistently outperformed individual base models in classifying GTV (area under the curve [AUC] = 0.928), brainstem (AUC = 0.932), and normal brain tissue (AUC = 0.942). Among the base models, the support vector machine model demonstrated the best performance in the three classifications (AUC = 0.922, 0.909, and 0.928). The higher performance of the stacked ensemble model highlighted the low performance of other models, including the decision tree (AUC = 0.709, 0.706, 0.804) and k-nearest neighbors (AUC = 0.721, 0.663, 0.729) models in certain contexts, such as when faced with high-dimensional feature spaces. While machine learning shows significant promise in medical image analysis, relying solely on a single model may lead to suboptimal results. By combining the strengths of various algorithms, the stacking ensemble model offers a better solution for the classification of brain metastases based on radiomic features., Competing Interests: Declarations Ethics approval and consent to participate According to the ethical guide-lines of the Helsinki Declaration and was approved by the institutional review board of Jiang-xi Cancer Hospital. Written informed consents were obtained from all patients prior to treatment. Informed consent forms were signed by all patients. The study was performed in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Jiang-xi Cancer Hospital (ethics number:2023KY082). Consent for publication Consent for publication is not applicable in this study, because there is not any individual person’s data. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Transthoracic echocardiography (TTE) is widely recognized as one of the principal modalities for diagnosing tricuspid regurgitation (TR). The diagnostic procedures associated with conventional methods are intricate and labor-intensive, with human errors leading to measurement variability, with outcomes critically dependent on the operators' diagnostic expertise. In this study, we present an innovative assessment methodology for evaluating TR severity utilizing an end-to-end deep learning system. This deep learning system comprises a segmentation model of single cardiac cycle TR continuous wave (CW) Doppler spectra and a classification model of the spectra, trained on the TR CW Doppler spectra from a cohort of 11,654 patients. The efficacy of this intelligent assessment methodology was validated on 1500 internal cases and 573 external cases. The receiver operating characteristic (ROC) curves of the internal validation results indicate that the deep learning system achieved the areas under curve (AUCs) of 0.88, 0.84, and 0.89 for mild, moderate, and severe TR, respectively. The ROC curves of the external validation results demonstrate that the system attained the AUCs of 0.86, 0.79, and 0.87 for mild, moderate, and severe TR, respectively. Our study results confirm the feasibility and efficacy of this novel intelligent assessment method for TR severity., Competing Interests: Declarations Competing interests The authors declare no competing interests. Statement of ethics Our study is a retrospective study. Our research protocol was reviewed and approved by the Ethics Review Committee of our institution (no. 2023-407). Since the data collected in this study consist of images and diagnostic reports that are routinely stored during echocardiography examinations, the Ethics Committee also approved the waiver of informed consent for this study., (© 2024. The Author(s).)

With the development of laser scanners and machine learning, point cloud semantic segmentation plays a significant role in autonomous driving, scene reconstruction, human-computer interaction, and other fields. In recent years, point cloud semantic segmentation based on deep learning has become one of the key research directions in point cloud processing. Due to the limited ability to exploit geometric details and contextual information in point clouds, most methods that adopt encoder-decoder architecture lose local structural information easily, especially detailed features, and extract features insufficiently. To address this issue, the edge-preserving inception DenseGCN U-Net (entitled as EIDU-Net) is proposed. EIDU-Net makes full use of the complementation between geometric details in the original point cloud and high-level features. The edge-preserved graph pooling (EGP) layer, the key module of the EIDU-Net, is designed to retain additional edge feature information from the original point cloud during pooling operations. Accordingly, the edge-preserved graph unpooling (EGU) layer can restore the feature graph more efficiently based on the additionally retained edge features. Extensive experiments demonstrate that our proposed EIDU-Net has remarkable improvements on semantic segmentation tasks under whatever S3DIS or Terracotta Warrior fragments. Our code is publicly available at https://github.com/caoxin918/EIDU-Net ., (© 2024. The Author(s).)

This study analysed the relationship between the structured and unstructured activities of preschoolers and their mental and physical health, and also investigated the predicted changes in mental and physical health by reallocating activity time. This cross-sectional study was carried out with 324 preschoolers. Video recording and SOPARC activity observation system was used for the division of structured and unstructured activities. An accelerometer sensor was used to measure activity intensity. The SDQ psychological questionnaire was adopted to collect data on internalizing difficulties, externalizing difficulties, total difficulties and pro-social behaviours. Physical indices including body shape (height, weight, BMI), and physical fitness (upper and lower limb strength, flexibility, agility, and balance) were collected using Chinese toddler physical fitness measurement tools. Component data and isotemporal reallocation analyses were conducted using R Studio (Version 4.2). A total of 308 preschoolers (160 boys; aged 4.50 ± 0.93 years) were included in the data analysis. The activities composition, adjusted for sex, area, mental level (for mental indicators), or age (for physical indicators), was significantly correlated with various measurement indicators (p < 0.05). Specifically, structured (β=-0.87, p < 0.05) and unstructured (β=-1.24, p < 0.05) moderate-to-vigorous physical activity (MVPA) were significantly positive correlated with internalizing difficulties, while structured MVPA was significantly positively correlated with body shape (β = 2.17, p < 0.05). Replacing structured light physical activity (LPA) with 10 min of structured MVPA has a positive effect on internalizing difficulties (SMD=-1.28, 95%CI: -2.30 to -0.27) and body shape (SMD = 1.76, 95%CI: 0.37 to 3.15). When the total replacement time reaches 25 min, the benefits become even more pronounced. Structured and unstructured MVPA are both beneficial to preschoolers' mental and physical health, with the incorporation of MVPA for over 25 min in structured activities and supplementary unstructured MVPA yielding even greater benefits., (© 2024. The Author(s).)

This study investigates the hydrocarbon generation potential of Jurassic source rocks under ultradeep conditions by utilizing semiclosed system hydrous pyrolysis experiments to simulate the geological processes at play. This study examines four distinct lithologies (shale, mudstone, carbonaceous mudstone, and coal) and three kerogen types (I, II, and III) across a temperature range of 250-650 °C and fluid pressures ranging from 34 to 100 MPa. The results indicate a bimodal distribution in total oil yields, with peak generation observed at approximately 350 °C and 600 °C. This pattern suggests a complex relationship between temperature, pressure, kerogen type, and hydrocarbon output. Notably, while I-Shale and II-Mudstone display higher hydrocarbon efficiency, III-type rocks exhibit superior oil and gas production rates because of their higher total organic carbon content. Research revealed that the oil expulsion rate exceeds 99% at temperatures above 500 °C, with the expelled oil predominantly comprising nonhydrocarbons and asphaltenes. Our findings suggest that Jurassic hydrocarbon source rocks maintain oil and gas potential under ultradeep conditions (high-over maturity stages at depths exceeding 6000 m). Under sustained fluid overpressure exceeding 70 MPa, the hydrocarbon generation peaks of various kerogen types in source rocks are markedly delayed. This phenomenon enables the source rocks to retain the potential for liquid hydrocarbon generation even during the stages of overmaturity. The results significantly enhance the theoretical framework of hydrocarbon generation under ultradeep conditions, thereby providing a crucial extension to the existing thermal boundary theory of hydrocarbon formation. These insights are crucial for the oil and gas industry, directing future exploration efforts towards ultradeep reservoirs and informing the development of new technologies to exploit these resources. This research not only enhances the understanding of subsurface hydrocarbon systems but also has implications for strategies aimed at maximizing resource recovery and managing the environmental impact of deep Earth exploration., (© 2024. The Author(s).)

To solve the issue of diagnosis accuracy of diabetic retinopathy (DR) and reduce the workload of ophthalmologists, in this paper we propose a prior-guided attention fusion Transformer for multi-lesion segmentation of DR. An attention fusion module is proposed to improve the key generator to integrate self-attention and cross-attention and reduce the introduction of noise. The self-attention focuses on lesions themselves, capturing the correlation of lesions at a global scale, while the cross-attention, using pre-trained vessel masks as prior knowledge, utilizes the correlation between lesions and vessels to reduce the ambiguity of lesion detection caused by complex fundus structures. A shift block is introduced to expand association areas between lesions and vessels further and to enhance the sensitivity of the model to small-scale structures. To dynamically adjust the model's perception of features at different scales, we propose the scale-adaptive attention to adaptively learn fusion weights of feature maps at different scales in the decoder, capturing features and details more effectively. The experimental results on two public datasets (DDR and IDRiD) demonstrate that our model outperforms other state-of-the-art models for multi-lesion segmentation., (© 2024. The Author(s).)

To investigate the association between single nucleotide polymorphism (SNP) at the rs3918188, rs1799983 and rs1007311 loci of the endothelial nitric oxide synthase (eNOS) gene and genetic susceptibility to systemic lupus erythematosus (SLE) in northeastern China. The base distribution of eNOS gene rs3918188, rs1799983 and rs1007311 in 1712 human peripheral blood samples from Northeast China was detected by SNaPshot sequencing technology. The correlation between genotype, allele and gene model of these loci of the eNOS gene and the genetic susceptibility to SLE was investigated by logistic regression analysis. The results of the differences in the frequency distribution of their gene models were visualised using R 4.3.2 software. Finally, HaploView 4.2 software was used to analyse the relationship between the haplotypes of the three loci mentioned above and the genetic susceptibility to SLE. A multifactor dimensionality reduction (MDR) analysis was used to determine the best SNP-SNP interaction model. The CC genotype and C allele at the rs3918188 locus may be a risk factor for SLE (CC vs AA: OR = 1.827, P < 0.05; C vs A: OR = 1.558, P < 0.001), and this locus increased the risk of SLE in the dominant model and the recessive model (AC + CC vs AA: OR = 1.542, P < 0.05; CC vs AA + AC: OR = 1.707, P < 0.001), while the risk of SLE was reduced in the overdominant model (AC vs AA + CC: OR = 0.628, P < 0.001). The GT genotype and T allele at locus rs1799983 may be a protective factor for SLE (GT vs GG: OR = 0.328, P < 0.001; T vs G: OR = 0.438, P < 0.001) and this locus reduced the risk of SLE in the overdominant model (GT vs GG + TT: OR = 0.385, P < 0.001). There is a strong linkage disequilibrium between the rs1007311 and rs1799983 loci of the eNOS gene. Among them, the formed haplotype AG increased the risk of SLE compared to GG. AT and GT decreased the risk of SLE compared to GG. In this study, the eNOS gene rs3918188 and rs1799983 loci were found to be associated with susceptibility to SLE. This helps to deeply explore the mechanism of eNOS gene and genetic susceptibility to SLE. It provides a certain research basis for the subsequent exploration of the molecular mechanism of these loci and SLE, as well as the early diagnosis, treatment and prognosis of SLE., (© 2024. The Author(s).)

To assess the impact of Enhanced Recovery After Surgery (ERAS) protocol in children undergoing corrective surgery for congenital scoliosis. A retrospective analysis was conducted on children undergoing surgical correction for congenital scoliosis, with participants categorized into either the ERAS group or the control group. Comparative evaluations were made across clinical, surgical, laboratory, and quality of life parameters. Following propensity score matching, 156 patients were analyzed. Within the initial 3 days following surgery, the ERAS cohort demonstrated lower pain intensity and exhibited higher daily oral intake compared to their counterparts in the control group. A mere 14.1% of patients in the ERAS group experienced a peak body temperature exceeding 38.5°, illustrating a significantly lower incidence compared to the 33.3% recorded in the control group. The ERAS cohort displayed expedited timeframes for the onset of initial bowel function and postoperative discharge when contrasted with the control group. Levels of IL-6 assessed on the third day post-surgery were markedly reduced in the ERAS group in comparison to the control group. Noteworthy is the similarity observed in postoperative hemoglobin and albumin levels measured on the first and third postoperative days between the two groups. Assessments of quality of life using SF-36 and SRS-22r questionnaires revealed comparable scores across all domains in the ERAS group when juxtaposed with the control cohort. ERAS protocol has demonstrated a capacity to bolster early perioperative recovery, alleviate postoperative stress responses, and uphold favorable quality of life outcomes in children undergoing corrective surgery for congenital scoliosis., (© 2024. The Author(s).)

Federated learning (FL) has emerged as a significant method for developing machine learning models across multiple devices without centralized data collection. Candidemia, a critical but rare disease in ICUs, poses challenges in early detection and treatment. The goal of this study is to develop a privacy-preserving federated learning framework for predicting candidemia in ICU patients. This approach aims to enhance the accuracy of antifungal drug prescriptions and patient outcomes. This study involved the creation of four predictive FL models for candidemia using data from ICU patients across three hospitals in China. The models were designed to prioritize patient privacy while aggregating learnings across different sites. A unique ensemble feature selection strategy was implemented, combining the strengths of XGBoost's feature importance and statistical test p values. This strategy aimed to optimize the selection of relevant features for accurate predictions. The federated learning models demonstrated significant improvements over locally trained models, with a 9% increase in the area under the curve (AUC) and a 24% rise in true positive ratio (TPR). Notably, the FL models excelled in the combined TPR + TNR metric, which is critical for feature selection in candidemia prediction. The ensemble feature selection method proved more efficient than previous approaches, achieving comparable performance. The study successfully developed a set of federated learning models that significantly enhance the prediction of candidemia in ICU patients. By leveraging a novel feature selection method and maintaining patient privacy, the models provide a robust framework for improved clinical decision-making in the treatment of candidemia., (© 2024. The Author(s).)

Artificial intelligence (AI) decision support systems in pediatric healthcare have a complex application background. As an AI decision support system (AI-DSS) can be costly, once applied, it is crucial to focus on its performance, interpret its success, and then monitor and update it to ensure ongoing success consistently. Therefore, a set of evaluation indicators was explicitly developed for AI-DSS in pediatric healthcare, enabling continuous and systematic performance monitoring. The study unfolded in two stages. The first stage encompassed establishing the evaluation indicator set through a literature review, a focus group interview, and expert consultation using the Delphi method. In the second stage, weight analysis was conducted. Subjective weights were calculated based on expert opinions through analytic hierarchy process, while objective weights were determined using the entropy weight method. Subsequently, subject and object weights were synthesized to form the combined weight. In the two rounds of expert consultation, the authority coefficients were 0.834 and 0.846, Kendall's coordination coefficient was 0.135 in Round 1 and 0.312 in Round 2. The final evaluation indicator set has three first-class indicators, fifteen second-class indicators, and forty-seven third-class indicators. Indicator I-1(Organizational performance) carries the highest weight, followed by Indicator I-2(Societal performance) and Indicator I-3(User experience performance) in the objective and combined weights. Conversely, 'Societal performance' holds the most weight among the subjective weights, followed by 'Organizational performance' and 'User experience performance'. In this study, a comprehensive and specialized set of evaluation indicators for the AI-DSS in the pediatric outpatient clinic was established, and then implemented. Continuous evaluation still requires long-term data collection to optimize the weight proportions of the established indicators., (© 2024. The Author(s).)

With the development of cloud computing, users are more inclined to outsource complex computing tasks to cloud servers with strong computing capacity, and the cloud returns the final calculation results. However, the cloud is not completely trustworthy, which may leak the data of user and even return incorrect calculations on purpose. Therefore, it is important to verify the results of computing tasks without revealing the privacy of the users. Among all the computing tasks, the polynomial calculation is widely used in information security, linear algebra, signal processing and other fields. Most existing polynomial-based verifiable computation schemes require that the input of the polynomial function must come from a single data source, which means that the data must be signed by a single user. However, the input of the polynomial may come from multiple users in the practical application. In order to solve this problem, the researchers have proposed some schemes for multi-source outsourced data, but these schemes have the common problem of low efficiency. To improve the efficiency, this paper proposes an efficient polynomial-based verifiable computation scheme on multi-source outsourced data. We optimize the polynomials using Horner's method to increase the speed of verification, in which the addition gate and the multiplication gate can be interleaved to represent the polynomial function. In order to adapt to this structure, we design the corresponding homomorphic verification tag, so that the input of the polynomial can come from multiple data sources. We prove the correctness and rationality of the scheme, and carry out numerical analysis and evaluation research to verify the efficiency of the scheme. The experimental indicate that data contributors can sign 1000 new data in merely 2 s, while the verification of a delegated polynomial function with a power of 100 requires only 18 ms. These results confirm that the proposed scheme is better than the existing scheme., (© 2024. The Author(s).)

In order to improve the response capability of cross regional emergency material scheduling (CREMS), a CREMS algorithm based on seed optimization algorithm is proposed. Construct a segmented regional grid distribution model structure for CREMS, use a grid matching algorithm based on block link distribution to construct the optimization objective function during the emergency material scheduling process, use variable neighborhood search technology to solve the diversity problem of cluster optimization in CREMS, and combine seed optimization algorithms for combination control and recursive analysis in the emergency material scheduling process. Based on the combination of deep learning and reinforcement learning, the optimal route and configuration scheme design for CREMS process is achieved. The simulation results show that this method has better active configuration capability, better path optimization capability and stronger spatial regional planning capability for CREMS., (© 2023. The Author(s).)

Cuproptosis is a recently discovered novel programmed cell death pathway that differs from traditional programmed cell death and has an important role in cancer and immune regulation. Long noncoding RNA (lncRNA) is considered new potential prognostic biomarkers in pancreatic adenocarcinoma (PAAD). However, the prognostic role and immune landscape of cuproptosis-related lncRNA in PAAD remain unclear. The transcriptome and clinical data of PAAD were obtained from The Cancer Genome Atlas (TCGA) database. Cuproptosis-related lncRNA was identified using Pearson correlation analysis. The optimal lncRNA was screened by Cox and the Least Absolute Shrinkage and Selection Operator (LASSO) regression mode, and for the construction of risk scoring system. PAAD patients were divided into high- and low-risk groups according to the risk score. Clinicopathological parameter correlation analysis, univariate and multivariate Cox regression, time-dependent receiver operating characteristic (ROC) curves, and nomogram were performed to evaluate the model. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to explore differences in biological function between different risk groups. Single-sample gene set enrichment analysis (ssGSEA) and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm were used to analyze the differences in tumor immune microenvironment (TIME) in different risk groups of PAAD. Additionally, the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm was used to predict immunotherapy response and identify potential immune beneficiaries. Immune checkpoints and tumor mutation burden (TMB) were also systematically analyzed. Finally, drug sensitivity analysis was used to explore the reactivity of different drugs in high- and low-risk groups to provide a reference for the selection of precise therapeutic drugs. Six cuproptosis-related lncRNAs (AL117335.1, AC044849.1, AL358944.1, ZNF236-DT, Z97832.2, and CASC8) were used to construct risk model. Survival analysis showed that overall survival and progression-free survival in the low-risk group were better than those in the high-risk group, and it is suitable for PAAD patients with different clinical characteristics. Univariate and multifactorial Cox regression analysis showed that risk score was an independent prognostic factor in PAAD patients. ROC analysis showed that the AUC values of the risk score in 1 year, 3 years and 5 years were 0.707,0.762 and 0.880, respectively. Nomogram showed that the total points of PAAD patients at 1 year, 3 years, and 5 years were 0.914,0.648, and 0.543. GO and KEGG analyses indicated that the differential genes in the high- and low-risk groups were associated with tumor proliferation and metastasis and immune regulatory pathway. Immune correlation analysis showed that the amount of pro-inflammatory cells, including CD8 + T cells, was significantly higher in the low-risk group than in the high-risk group, and the expression of immune checkpoint genes, including PD-1 and CTLA-4, was increased in the low-risk group. TIDE analysis suggests that patients in the low-risk group may benefit from immunotherapy. Finally, there was significant variability in multiple chemotherapeutic and targeted drugs across the risk groups, which informs our clinical drug selection. Our cuproptosis-related lncRNA scoring system (CRLss) could predict the clinical outcome and immune landscape of PAAD patients, identify the potential beneficiaries of immunotherapy, and provide a reference for precise therapeutic drug selection., (© 2023. The Author(s).)

The impact of N221S mutation in hRRM2B gene, which encodes the small subunit of human ribonucleotide reductase (RNR), on RNR activity and the pathogenesis of mitochondrial DNA depletion syndrome (MDDS) was investigated. Our results demonstrate that N221 mutations significantly reduce RNR activity, suggesting its role in the development of MDDS. We proposed an allosteric regulation pathway involving a chain of three phenylalanine residues on the αE helix of RNR small subunit β. This pathway connects the C-terminal loop of β2, transfers the activation signal from the large catalytic subunit α to β active site, and controls access of oxygen for radical generation. N221 is near this pathway and likely plays a role in regulating RNR activity. Mutagenesis studies on residues involved in the phenylalanine chain and the regulation pathway were conducted to confirm our proposed mechanism. We also performed molecular dynamic simulation and protein contact network analysis to support our findings. This study sheds new light on RNR small subunit regulation and provides insight on the pathogenesis of MDDS., (© 2023. The Author(s).)

Green innovation plays a crucial role in transforming economic models and achieving sustainable development in enterprises. As an important embodiment of artificial intelligence technology, how industrial robots can effectively promote the green transformation of enterprises has become an important issue. This paper examines the impact and mechanisms of industrial robot adoption on corporate green innovation, as well as its heterogeneous effects. Using data from Chinese listed companies from 2007 to 2019, we find that industrial robot adoption has a significant positive impact on corporate green innovation, enhancing both its quantity and quality. Furthermore, our mechanism study reveals that industrial robot adoption can promote corporate green innovation by improving productivity and environmental management capabilities. Additionally, we investigate the moderating effects of various factors and conclude that the positive impact of industrial robot adoption on green innovation is more pronounced among the state-owned enterprises, enterprises with the intense market competition, as well as enterprises located in regions with higher carbon emissions intensity. This paper contributes to enrich the research on industrial robots and corporate green innovation, and provides a reference to improve environmental management and achieve a low-carbon economy in emerging markets., (© 2023. The Author(s).)

A structurally dense hydrogel, with strong hydrogen bonding networks, was formed from poly(vinyl alcohol), sodium alginate, and oligomeric proanthocyanidins, using a combination of freeze-thaw cycles and calcium ion cross-linking. The structure of the hydrogel was characterized by scanning electron microscopy and Fourier transform infrared spectroscopy. Mechanical testing and thermogravimetric analysis showed that incorporation of proanthocyanidins enhanced both the mechanical properties and the thermal stability of the hydrogel. The hydrogel was also demonstrated to have excellent ultraviolet resistance and antioxidant properties. The hydrogel was further shown that this hydrogel is also capable of generating electrochemical reactions, which strongly suggests that this hydrogel has exciting potential in many fields., (© 2023. Springer Nature Limited.)

Fault rupture is a common phenomenon in geotechnical engineering. To prevent rupture, laneway shoring is performed, prior to which, convergence deformation, failure criteria, and fracture development in soft rocks in the fault rupture zone are carefully analyzed. Then, a supporting structure corresponding to the actual situation of the soft rock in the rupture zone is created. Herein, the water-rich laneway shoring through the fault rupture zone of the Hongqingliang coal mine located in the Inner Mongolia Autonomous Region is taken as the research object. Then, the fracture development and characteristics of argillaceous siltstones and laneway shoring cross-fault rupture zone are studied. Site inspection, indoor and field tests, theoretical analysis, numerical simulation, and field monitoring were used for systematic fracture analysis. Results indicated that laneway shoring through the fault fracture zone in the Hongqingliang coal mine could help prevent disasters. This method was extended to laneway supports built through the fault rupture zones in mines in other areas of China., (© 2023. The Author(s).)

To improve the prediction accuracy of traffic flow under the influence of nearby time traffic flow disturbance, a dynamic spatiotemporal graph attention network traffic flow prediction model based on the attention mechanism was proposed. Considering the macroscopic periodic characteristics of traffic flow, the spatiotemporal features are extracted by constructing spatiotemporal blocks with an adjacent period, daily period, and weekly period respectively. The spatiotemporal block is mainly composed of a two-layer graph attention network and a gated recurrent unit to capture the hidden features of space and time. In space, based on considering adjacent road segments, the Pearson correlation coefficient is used to capture the hidden correlation characteristics between non-adjacent road segments according to a certain time step. In terms of time, due to the random disturbance of traffic flow at the micro level, the attention mechanism is introduced to use the adjacent time as the query matrix to weight the output characteristics of daily cycle and weekly cycle, and the three are connected in series to output the prediction results through the linear layer. Finally, the experimental results on the public data sets show that the proposed model is superior to the six baseline models., (© 2023. Springer Nature Limited.)

Meteorological conditions and irrigation amounts are key factors that affect crop growth processes. Typically, crop growth and development are modeled as a function of time or growing degree days (GDD). Although the most important component of GDD is temperature, it can vary significantly year to year while also gradually shifting due to climate changes. However, cotton is highly sensitive to various meteorological factors, and reference crop evapotranspiration (ET O ) integrates the primary meteorological factors responsible for global dryland extension and aridity changes. This paper constructs a cotton growth model using ET O , which improves the accuracy of crop growth simulation. Two cotton growth models based on the logistic model established using GDD or ET O as independent factors are evaluated in this paper. Additionally, this paper examines mathematical models that relate irrigation amount and irrigation water utilization efficiency (IWUE) to the maximum leaf area index (LAI max ) and cotton yield, revealing some key findings. First, the model using cumulative reference crop evapotranspiration (CET O ) as the independent variable is more accurate than the one using cumulative growing degree days. To better reflect the effects of meteorological conditions on cotton growth, this paper recommends using CET O as the independent variable to establish cotton growth models. Secondly, the maximum cotton yield is 7171.7 kg/ha when LAI max is 6.043 cm 2 /cm 2 , the corresponding required irrigation amount is 518.793 mm, and IWUE is 21.153 kg/(ha·mm). Future studies should consider multiple associated meteorological factors and use ET O crop growth models to simulate and predict crop growth and yield., (© 2023. The Author(s).)

Numerous studies have evaluated the use of single nucleotide polymorphism array (SNP-array) in prenatal diagnostics, but very few have evaluated its application under different risk conditions. Here, SNP-array was used for the retrospective analysis of 8386 pregnancies and the cases were categorized into seven groups. Pathogenic copy number variations (pCNVs) were found in 699 (8.3%, 699/8386) cases. Among the seven different risk factor groups, the non-invasive prenatal testing-positive group had the highest pCNVs rate (35.3%), followed by the abnormal ultrasound structure group (12.8%), and then the chromosomal abnormalities in the couples group (9.5%). Notably the adverse pregnancy history group presented with the lowest pCNVs rate (2.8%). Further evaluation of the 1495 cases with ultrasound abnormalities revealed that the highest pCNV rates were recorded in those cases with multiple system structure abnormalities (22.6%), followed by the groups with skeletal system (11.6%) and urinary system abnormalities (11.2%). A total of 3424 fetuses with ultrasonic soft markers were classified as having one, two, or three ultrasonic soft markers. The different pCNV rates in the three groups were statistically significant. There was little correlation between pCNVs and a previous history of adverse pregnancy outcomes, suggesting that genetic screening under these conditions should be evaluated on a case-by-case basis., (© 2023. The Author(s).)

Although opioids are necessary for the treatment of acute pain, cancer pain, and palliative care, opioid abuse is a serious threat to society. Heroin (Diacetylmorphine) is the most commonly abused opioid, and it can have a variety of effects on the body's tissues and organs, including the well-known gastrointestinal depression and respiratory depression; however, there is little known about the effects of diacetylmorphine on cardiac damage. Here, we demonstrate that diacetylmorphine induces abnormal electrocardiographic changes in rats and causes damage to cardiomyocytes in vitro by an underlying mechanism of increased autophosphorylation of CaMKII and concomitant regulation of myocardial contractile protein TPM1 and MYOM2 protein expression. The CaMKII inhibitor KN-93 was first tested to rescue the toxic effects of heroin on cardiomyocytes in vitro and the abnormal ECG changes caused by heroin in SD rats, followed by the TMT relative quantitative protein technique to analyze the proteome changes. Diacetylmorphine causes increased phosphorylation at the CaMKII Thr287 site in myocardium, resulting in increased autophosphorylation of CaMKII and subsequent alterations in myocardial contractile proteins, leading to myocardial rhythm abnormalities. These findings provide a theoretical basis for the treatment and prevention of patients with arrhythmias caused by diacetylmorphine inhalation and injection., (© 2023. The Author(s).)

Septic shock, largely caused by intestinal perforation, is a common critical disease in intensive care unit (ICU). For hospitals and health systems, a performance improvement program for sepsis was strong recommended in guidelines. Numerous studies have shown that improved quality control improves outcomes in patients with septic shock. Nevertheless, association between quality control and outcomes of septic shock caused by intestinal perforation are not fully revealed. Thus we designed this study to investigate effects of quality control on septic shock caused by intestinal perforation in China. This was a multicenter observational study. A total of 463 hospitals were enrolled in this survey, led by the China National Critical Care Quality Control Center (China-NCCQC) from January 1, 2018 to December 31, 2018. In this study, the indicators of quality control included the proportion of ICU patient bed occupancy to total inpatient bed occupancy, the proportion of ICU patients with APACHE II score ≥ 15, and the microbiology detection rate before antibiotic use. The outcome indicators included hospital stays, hospitalization costs, complications, and mortality. Generalized linear mixed models were used to analyse the association between quality control and septic shock caused by intestinal perforation. The proportion of ICU patient bed occupancy to total inpatient bed occupancy is positively correlated with hospital stays, incidence of complications (ARDS, AKI) and costs in septic shock caused by intestinal perforation (p < 0.05). The proportion of ICU patients with APACHE II score ≥ 15 was not associated with hospital stays and incidence of ARDS and AKI (p < 0.05). Increasing of the proportion of ICU patients with APACHE II score ≥ 15 decreased the costs of patients with septic shock caused by intestinal perforation (p < 0.05). The microbiology detection rate before antibiotic use was not associated with hospital stays, incidence of AKI and costs of patients with septic shock caused by intestinal perforation (p < 0.05). Surprisingly, the increase of microbiology detection rate before antibiotic use increased the incidence of ARDS in patients with septic shock caused by intestinal perforation (p < 0.05). The above three indicators of quality control were not associated with mortality of the patients with septic shock caused by intestinal perforation. On the one hand, the number of ICU patients admitted should be controlled to reduce the proportion of ICU patients out of total inpatient bed occupancy. On the other hand, intensive care unit admission of severe patients (patients with APACHE II score ≥ 15) should be encouraged to improve the proportion of patients with APACHE II score ≥ 15 in the ICU, so that ICU can focus more on the treatment of severe patients and promote the professionalization of severe patient management. It is not advisable to collect sputum specimens too frequently for patients without pneumonia., (© 2023. The Author(s).)

Gut microbiota dysbiosis is already a global problem after antibiotic overuse. This study was to investigate the therapeutic effect of lentinan and the mechanism of recovery of intestinal inflammation on broad-spectrum antibiotic-driven gut microbial dysbiosis in mice. Gut microbiota was elucidated by the Illumina MiSeq platform. Gas chromatography/mass spectrometry was used to investigate short-chain fatty acid content. Colon histology, expression of tight-junction associated proteins and pro-inflammatory cytokines levels were evaluated. The results showed that the gut microbiota of diversity and richness were reduced and various taxonomic levels of the gut microbiota were perturbed after antibiotics gavage. The abundance of Firmicutes and Bacteroidetes shifted to Proteobacteria and increased the relative abundance of harmful microbiota (Parabacteroides and Klebsiella) post-antibiotics, whereas lentinan administration reversed the dysbiosis and increased beneficial microbiota, including S24-7, Lactobacillus, Oscillospira, Ruminococcus and Allobaculum. The concentrations of propionic acid and butyric acid were significantly increased by treatment with lentinan. And lentinan improved colon tissue morphology and reduced pro-inflammatory cytokines via altering NF-κB signaling pathway in antibiotic-driven gut microbial dysbiosis mice. Taken together, the results proved that lentinan can be used as a prebiotic and the result provided a theoretical basis for improving the clinical treatment of broad-spectrum antibiotics side effects., (© 2022. The Author(s).)

Optical fiber bending, deformation or shape sensing are important measurement technologies and have been widely deployed in various applications including healthcare, structural monitoring and robotics. However, existing optical fiber bending sensors require complex sensor structures and interrogation systems. Here, inspired by the recent renewed interest in information-rich multimode optical fibers, we show that the multimode fiber (MMF) output speckles contain the three-dimensional (3D) geometric shape information of the MMF itself. We demonstrate proof-of-concept 3D multi-point deformation sensing via a single multimode fiber by using k-nearest neighbor (KNN) machine learning algorithm, and achieve a classification accuracy close to 100%. Our results show that a single MMF based deformation sensor is excellent in terms of system simplicity, resolution and sensitivity, and can be a promising candidate in deformation monitoring or shape-sensing applications., (© 2022. The Author(s).)

Revealing the structural morphology and inner flow field of the upper airway is important for understanding obstructive sleep apnea-hypopnea syndrome (OSAHS) incidence phenomena and pathological diagnosis in children. However, prior work on this topic has been focused on adults and the findings cannot be directly extrapolated to children because of different inducing factors. Therefore, this paper employs a simulation method to investigate upper airway flow characteristics of childhood OSAHS. It is found that the Reynold number changes highly throughout the whole upper airway, and the laminar assumption is no longer suitable for low Reynold number flow, which is much unlike classic fluid mechanics. Turbulent models of Standard k-ω and Spalart-Allmaras were developed prior to suggestion. The simulation is validated by experiments with an error of approximately 20%. Additionally, carried out in this analysis is the influence of adenoidal hypertrophy with different narrow levels. The cross-sectional area, flow velocity, pressure drop and volume rate will change greatly when the narrow level is above 64% of the upper airway, which can be a quantitative explanation for medical intervention if adenoid hypertrophy blocks 2/3 of the upper airway in the common clinical judgment of otorhinolaryngology. It is expected that this paper can be a meaningful instruction on OSAHS surgery plan making as well as recovery evaluation postoperatively., (© 2022. The Author(s).)

HIV subtypes convey important epidemiological information and possibly influence the rate of disease progression. In this study, HIV disease progression in patients infected with CRF01&#95;AE, CRF07&#95;BC, and subtype B was compared in the largest HIV molecular epidemiology study ever done in China. A national data set of HIV pol sequences was assembled by pooling sequences from public databases and the Beijing HIV laboratory network. Logistic regression was used to assess factors associated with the risk of AIDS at diagnosis ([AIDSAD], defined as a CD4 count < 200 cells/µL) in patients with HIV subtype B, CRF01&#95;AE, and CRF07&#95;BC. Of the 20,663 sequences, 9,156 (44.3%) were CRF01&#95;AE. CRF07&#95;BC was responsible for 28.3% of infections, followed by B (13.9%). In multivariable analysis, the risk of AIDSAD differed significantly according to HIV subtype (OR for CRF07&#95;BC vs. B: 0.46, 95% CI 0.39─0.53), age (OR for ≥ 65 years vs. < 18 years: 4.3 95% CI 1.81─11.8), and transmission risk groups (OR for men who have sex with men vs. heterosexuals: 0.67 95% CI 0.6─0.75). These findings suggest that HIV diversity in China is constantly evolving and gaining in complexity. CRF07&#95;BC is less pathogenic than subtype B, while CRF01&#95;AE is as pathogenic as B., (© 2022. The Author(s).)

Type 2 diabetes (T2D) is a major public health problem, and gut microbiota dysbiosis has been implicated in the emergence of T2D in humans. Dietary interventions can indirectly influence the health status of patients with type 2 diabetes through their modulatory effects on the intestinal microbiota. In recent years, fecal microbiota transplantation is becoming familiar as a new medical treatment that can rapidly improve intestinal health. We conducted a 90-day controlled open-label trial to evaluate the health improvement ability of a specially designed diet, and the diet combined with fecal microbiota transplantation (FMT). According to our study, both diet and diet plus FMT treatments showed great potential in controlling blood glucose and blood pressure levels. Sequencing the V4 region of 16S rRNA gene on the Illumina MiniSeq platform revealed a shift of intestinal microbial community in T2D patients, and the changes were also observed in response to the treatments. FMT changed the gut microbiota more quickly than diet. Beneficial bacterium, such as Bifidobacterium, increased along the study and was negatively correlated with blood glucose, blood pressure, blood lipid and BMI. Sulfate-reducing bacteria (SRB), Bilophila and Desulfovibrio, decreased significantly after treatment, showed a positive correlation with blood glucose indices. Thus, the specially designed diet is beneficial to improve blood glucose control in diabetic patients, it also showed the potential to reverse dyslipidemia and dysarteriotony., (© 2022. The Author(s).)

Calamansi or Philippine lime (Citrofortunella macrocarpa) is an important crop for local economic in Hainan Island. There is no study about Calamansi germplasm evaluation and cultivar development. In this study, Calamansi data were collected from 151 of Calamansi seedling trees, and 37 phenotypic traits were analyzed to investigate their genetic diversities. The cluster analysis and principal component analysis were conducted aiming to provide a theoretical basis for the Calamansi genetic improvement. The results of the diversity analysis revealed: (1) the diversity indexes for qualitative traits were ranged from 0.46-1.39, and the traits with the highest genetic diversity level were fruit shaped and pulp colored (H' > 1.20); and the diversity indexes for quantitative traits ranged from 0.67-2.10, with the exception of a lower in fruit juice rate (1.08) and lower in number of petals (0.67). (2) The clustering analysis of phenotypic traits have arranged the samples into 4 categories: the first group characterized by fewer flesh Segment number per fruit (SNF) and more Oil cell number (OCN); the second group had 7 samples, all characterized with larger Crown breadth (CB), higher Yield per tree (YPT), the lager leaf, the higher Ascorbic acid (AA), and less Seed number per fruit (SNPF); the third group had 25 samples characterized by smaller Tree foot diameter (TFD),smaller Fruit shape index (FSI) and higher Total soluble solids (TSS) contain; the fourth group had 87 samples, they were characterized by shorter Petiole length (PEL), larger fruit, higher Juice ratio (JR), multiple Stamen number (SN) and longer Pistil length (PIL). (3) The principal component analysis showed the values of the first 9 major components characteristic vectors were all greater than 3, the cumulative contribution rate reach 72.20%, including the traits of single fruit weight, fruit diameter, tree height, tree canopy width etc. Finally, based on the comprehensive main component value of all samples, the Calamansi individuals with higher testing scores were selected for further observation. This study concludes that Calamansi seedling populations in the Hainan Island holds great genetic diversity in varies traits, and can be useful for the Calamansi variety improvements., (© 2022. The Author(s).)

With the increased incidence and recognition, ulcerative colitis (UC) has become a global public health problem in the world. Although many immunosuppressant and biological drugs have been used for UC treatment, the cure rate is still very low. It is necessary to find some safe and long-term used medicine for UC cure. Recently, the Chinese traditional herb Danshen has been investigated in the treatment of UC. However, it is a limitation of Danshen that many of the active components in Danshen are not easily absorbed by the human body. Probiotics could convert macromolecules into smaller molecules to facilitate absorption. Thus, Lactobacillus rhamnosus (F-B4-1) and Bacillus subtillis Natto (F-A7-1) were screened to ferment Danshen in this study. The fermented Danshen products were gavaged in the dextran sulfate sodium (DSS)-induced UC model mice. Danshen had better results to attenuate symptoms of DSS-induced UC after fermented with F-B4-1 and F-A7-1. Loss of body weight and disease activity index (DAI) were reduced. The abnormally short colon lengths and colonic damage were recovered. And fermented Danshen had the better inhibitory effect than Danshen itself on pro-inflammatory cytokine expression during DSS-induced UC. The results indicated that compared with Danshen, fermented Danshen relieved DSS-induced UC in mice more effectively. Danshen fermented by probiotics might be an effective treatment to UC in clinic stage in the future., (© 2021. The Author(s).)

Phedimus aizoon L. is a drought-resistant Chinese herbal medicine and vegetable. However, its drought tolerant limit and the mechanism of drought tolerance are unknown, which restricts the promotion of water-saving cultivation of Phedimus aizoon L. in arid areas. To solve the above problem, we carried out a 30-day-long drought stress experiment in pots that presented different soil water contents and were divided into four groups: control check, 75-80% of the maximum water-holding capacity (MWHC); mild drought, 55-60%; moderate drought, 40-45%; and severe drought, 20-25%. The dynamic changes in both plant physiological indexes from 10 to 30 days and leaf anatomical structure on the 30th day of stress were recorded. The results show that Phedimus aizoon L. grew normally under mild drought stress for 30 days, but the growth of the plants became inhibited after 20 days of severe drought and after 30 days of moderate drought. At the same time, Phedimus aizoon L. physiologically responded to cope with drought stress: the growth of the root system accelerated, the waxy layer of the leaves thickened, and the dark reactions of the plants transformed from those of the C3 cycle to CAM. The activity of antioxidant enzymes (SOD, POD and CAT) continuously increased to alleviate the damage caused by drought stress. To ensure the relative stability of the osmotic potential, the contents of osmoregulatory substances such as proline, soluble sugars, soluble protein and trehalose increased correspondingly. Although Phedimus aizoon L. has strong drought stress resistance, our experimental results show that the soil available water content should not be less than 27% during cultivation.

Cervical cancer continues to impose a heavy burden worldwide, and human papilloma virus (HPV) infection, especially persistent infection with type 16 (HPV-16), is known to be the primary etiological factor. Therapeutic vaccines are urgently needed because prophylactic vaccines are ineffective at clearing pre-existing HPV infection. Here, two recombinant Listeria strains (LMΔ-E6E7 & LIΔ-E6E7) with deletions of the actA and plcB genes, expressing the shuffled HPV-16 E6E7 protein were constructed. The strains were delivered into the spleen and liver by intravenous inoculation, induced antigen-specific cellular immunity and were eliminated completely from the internal organs several days later. Intravenously treating with single strain for three times, or with both strains alternately for three times significantly reduced the tumor size and prolonged the survival time of model mice. Combination immunotherapy with two strains seemed more effective than immunotherapy with single strain in that it enhanced the survival of the mice, and the LMΔ-E6E7-prime-LIΔ-E6E7-boost strategy showed significant stronger efficacy than single treatment with the LIΔ-E6E7 strain. The antitumor effect of this treatment might due to its ability to increase the proportion of CD8 + T cells and reduce the proportion of T regulatory cells (Tregs) in the intratumoral milieu. This is the first report regarding Listeria ivanovii-based therapeutic vaccine candidate against cervical cancer. Most importantly we are the first to confirm that combination therapy with two different recombinant Listeria strains has a more satisfactory antitumor effect than administration of a single strain. Thus, we propose a novel prime-boost treatment strategy.

Ultraviolet A (UV-A) radiation is a significant environmental factor that causes photoreceptor damage, apoptosis, and oxidative stress in insects. Ostrinia furnacalis is an important pest of corn. To understand the adaptation mechanisms of insect response to UV-A exposure, this study revealed differentially expressed genes (DEGs) and differently expressed metabolites (DEMs) in O. furnacalis under UV-A exposure. Three complementary DNA libraries were constructed from O. furnacalis adult females (CK, UV1h, and UV2h), and 50,106 expressed genes were obtained through Illumina sequencing. Of these, 157 and 637 DEGs were detected in UV1h and UV2h after UV-A exposure for 1 and 2 h, respectively, compared to CK, with 103 and 444 upregulated and 54 and 193 downregulated genes, respectively. Forty four DEGs were detected in UV2h compared to UV1h. Comparative transcriptome analysis between UV-treated and control groups revealed signal transduction, detoxification and stress response, immune defense, and antioxidative system involvement. Metabolomics analysis showed that 181 (UV1h vs. CK), 111 (UV2h vs. CK), and 34 (UV2h vs. UV1h) DEMs were obtained in positive ion mode, while 135 (UV1h vs. CK), 93 (UV2h vs. CK), and 36 (UV2h vs. UV1h) DEMs were obtained in negative ion mode. Moreover, UV-A exposure disturbed amino acid, sugar, and lipid metabolism. These findings provide insight for further studies on how insects protect themselves under UV-A stress.

A new constitutive model for frozen soils under high strain rate is developed. By taking the frozen soil as a composite material and considering the adiabatic temperature rise and interfacial debonding damage, the nonlinear dynamic response (NDR) of the frozen soil is predicted. At the same time, the relationship between instantaneous temperature and unfrozen water content is given, and an evolution rule of the volume fraction of ice particles is obtained. This relationship shows good agreement with experimental data. Using this new constitutive model, the stress-strain relationship of frozen soil under impact loading at temperatures of - 3 °C, - 8 °C, - 18 °C, and - 28 °C is calculated. There is good agreements between the results based on this new constitutive model and the data of dynamic impact.

The mammalian high mobility group protein AT-hook 2 (HMGA2) is a multi-functional DNA-binding protein that plays important roles in tumorigenesis and adipogenesis. Previous results showed that HMGA2 is a potential therapeutic target of anticancer and anti-obesity drugs by inhibiting its DNA-binding activities. Here we report the development of a miniaturized, automated AlphaScreen ultra-high-throughput screening assay to identify inhibitors targeting HMGA2-DNA interactions. After screening the LOPAC1280 compound library, we identified several compounds that strongly inhibit HMGA2-DNA interactions including suramin, a century-old, negatively charged antiparasitic drug. Our results show that the inhibition is likely through suramin binding to the "AT-hook" DNA-binding motifs and therefore preventing HMGA2 from binding to the minor groove of AT-rich DNA sequences. Since HMGA1 proteins also carry multiple "AT-hook" DNA-binding motifs, suramin is expected to inhibit HMGA1-DNA interactions as well. Biochemical and biophysical studies show that charge-charge interactions and hydrogen bonding between the suramin sulfonated groups and Arg/Lys residues play critical roles in the binding of suramin to the "AT-hook" DNA-binding motifs. Furthermore, our results suggest that HMGA2 may be one of suramin's cellular targets.

Calcium is an important mineral that plays an integral role in human health, especially bone health. Marine biological calcium is an abundant resource that is generally accepted and has a complex active structure. This review evaluates research progress on marine biological calcium with regards to its sources, use of calcium supplements, calcium bioavailability, and novel applications of marine calcium. The potential for future development and the use of products incorporating marine biological calcium in biomedical research and the pharmaceutical, health care, and food industries are also reviewed. The goal of this review is to provide a comprehensive documentation on resource utilization and product development from marine organisms.

A catastrophic landslide disaster happened on 2 August 2014 on the right bank of Sunkoshi River in Nepal, resulting in enormous casualties and severe damages of the Araniko highway. We collected multi-source synthetic aperture radar (SAR) data to investigate the evolution life cycle of the Sunkoshi landslide. Firstly, Distributed Scatterers SAR Interferometry (DS-InSAR) technology is applied to analyze 20 ALOS PALSAR images to retrieve pre-disaster time-series deformation. The results show that the upper part, especially the top of the landslide, has long been active before collapse, with the largest annual LOS deformation rate more than - 30 mm/year. Time series deformations measured illustrate that rainfall might be a key driving factor. Next, two pairs of TerraSAR-X/TanDEM-X bistatic data are processed to identify the landslide affected area by intensity change detection, and to generate pre- and post-disaster DSMs. Surface height change map showed maximum values of - 150.47 m at the source region and 55.65 m in the deposit region, leading to a debris volume of 5.4785 ± 0.6687 million m 3 . Finally, 11 ALOS-2 PALSAR-2 and 82 Sentinel-1 SAR images are analyzed to derive post-disaster annual deformation rate and long time series displacements of the Sunkoshi landslide. The results illustrated that the upper part of the landslide were still in active deformation with the largest LOS displacement velocity exceeding - 100 mm/year.

Transforming growth factor beta-1 (TGFβ1) is a major driver of vascular smooth muscle cell (VSMC) phenotypic switching, an important pathobiology in arterial disease. We performed RNA-sequencing of TGFβ1-stimulated human aortic or arterial VSMCs which revealed large and consistent upregulation of Interleukin 11 (IL11). IL11 has an unknown function in VSMCs, which highly express the IL11 receptor alpha, suggestive of an autocrine loop. In vitro, IL11 activated ERK signaling, but inhibited STAT3 activity, and caused VSMC phenotypic switching to a similar extent as TGFβ1 or angiotensin II (ANGII) stimulation. Genetic or therapeutic inhibition of IL11 signaling reduced TGFβ1- or ANGII-induced VSMC phenotypic switching, placing IL11 activity downstream of these factors. Aortas of mice with Myh11-driven IL11 expression were remodeled and had reduced contractile but increased matrix and inflammatory genes expression. In two models of arterial pressure loading, IL11 was upregulated in the aorta and neutralizing IL11 antibodies reduced remodeling along with matrix and pro-inflammatory gene expression. These data show that IL11 plays an important role in VSMC phenotype switching, vascular inflammation and aortic pathobiology.

Experimental animals including the ferret, marmoset, woodchuck, mini pig, and tree shrew have been used in biomedical research. However, their gut microbiota have not been fully investigated. In this study, the gut microbiota of these five experimental animals were analyzed with 16S rRNA sequencing. The phyla Firmicutes, Bacteroidetes, and Fusobacteria were present in the gut microbiota of all the species. Specific phyla were present in different animals: Proteobacteria in the ferret, Tenericutes in the marmoset, and Spirochaetes in the mini pig. Fusobacterium and unidentified Clostridiales were the dominant genera in the ferret, whereas Libanicoccus, Lactobacillus, Porphyromonas, and Peptoclostridium were specific to marmoset, mini pig, woodchuck, and tree shrew, respectively. A clustering analysis showed that the overall distribution of microbial species in the guts of these species mirrored their mammalian phylogeny, and the microbiota of the marmoset and tree shrew showed the closest bray&#95;curtis distances to that of humans. PICRUSt functional prediction separated the woodchuck from the other species, which may reflect its herbivorous diet. In conclusion, both the evolutionary phylogeny and daily diet affect the gut microbiota of these experimental animals, which should not be neglected for their usage in biomedical research.

Many fetuses are found to have ultrasonic abnormalities in the late pregnancy. The association of fetal ultrasound abnormalities in late pregnancy with copy number variations (CNVs) is unclear. We attempted to explore the relationship between types of ultrasonically abnormal late pregnancy fetuses and CNVs. Fetuses (n = 713) with ultrasound-detected abnormalities in late pregnancy and normal karyotypes were analyzed. Of these, 237 showed fetal sonographic structural malformations and 476 showed fetal non-structural abnormalities. Single nucleotide polymorphism (SNP)-based chromosomal microarray (CMA) was performed on the Affymetrix CytoScan HD platform. Using the SNP array, abnormal CNVs were detected in 8.0% (57/713) of the cases, with pathogenic CNVs in 32 cases and variants of uncertain clinical significance (VUS) in 25 cases. The detection rate of abnormal CNVs in fetuses with sonographic structural malformations (12.7%, 30/237) was significantly higher (P = 0.001) than that in the fetuses with non-structural abnormalities (5.7%, 27/476). Overall, we observed that when fetal sonographic structural malformations or non-structural abnormalities occurred in the third trimester of pregnancy, the use of SNP analysis could improve the accuracy of prenatal diagnosis and reduce the rate of pregnancy termination.

Recent reports have shown that intracellular, (super)paramagnetic ferritin nanoparticles can gate TRPV1, a non-selective cation channel, in a magnetic field. Here, we report the effects of differing field strength and frequency as well as chemical inhibitors on channel gating using a Ca 2+ -sensitive promoter to express a secreted embryonic alkaline phosphatase (SEAP) reporter. Exposure of TRPV1-ferritin-expressing HEK-293T cells at 30 °C to an alternating magnetic field of 501 kHz and 27.1 mT significantly increased SEAP secretion by ~ 82% relative to control cells, with lesser effects at other field strengths and frequencies. Between 30-32 °C, SEAP production was strongly potentiated 3.3-fold by the addition of the TRPV1 agonist capsaicin. This potentiation was eliminated by the competitive antagonist AMG-21629, the NADPH oxidase assembly inhibitor apocynin, and the reactive oxygen species (ROS) scavenger N-acetylcysteine, suggesting that ROS contributes to magnetogenetic TRPV1 activation. These results provide a rational basis to address the heretofore unknown mechanism of magnetogenetics.

Intraosseous arteriovenous malformations in jaws (j-AVMs) are rare congenital high-flow vascular anomalies with a high tendency of life-threatening haemorrhage and are regarded as one of the most dangerous haemorrhagic diseases in maxillofacial region. Pre-treatment clinical and imaging evaluations serve as the most important diagnostic modalities. A retrospective study involved 211 patients with j-AVMs from November 2003 to November 2017 was performed. The male-to-female ratio of j-AVMs was approximately 4:3. The mean age of the patients with j-AVMs is 21.86. Bleeding was the main complaint associated with j-AVMs. J-AVMs occurred in the mandible more often than in the maxilla (64.93% and 32.23%, respectively). Most j-AVMs (95.26%) occurred in the posterior teeth region. Classical imaging features of j-AVMs included: an unclear maxillary sinus with a mild ground-glass appearance (maxillary j-AVMs) and a clear oval or irregular lucency that is mostly centred on the root of the first molar (mandibular j-AVMs) on OPGs, enhancement in the cancellous bone on contrast-enhanced CTs. Other atypical features of j-AVMs were also concluded. A comprehensive diagnose system based on clinical and imaging features of j-AVMs could provide valuable reference data for clinical management of j-AVMs and help avoid improper iatrogenic trauma or delayed treatment.