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To solve the problem of poor thermal stability of the current D-allulose 3-epimerase (DAEase), the ancestor sequences of DAEase with different catalytic domains were reconstructed by big data mining, reasonable modification and ancestor sequence reconstruction (ASR) strategy under the guidance of phylogenetic information. The expression vectors of the ancestor sequences were constructed, and DAEase A13 with significantly enhanced thermal stability was screened by recombinant expression and molecular docking, and its enzymatic properties were characterized. In addition, the molecular mechanism of thermal stability enhancement of DAEase A13 was revealed based on structural analysis and molecular dynamics. The results showed that the half-life of A13 constructed based on ASR strategy could reach 8.4 h at 70 ℃, indicating that its thermal stability was significantly enhanced compared with that of wild-type (WT) enzyme. The maximum conversion rate of A13 reached 31%, indicating that the catalytic activity of A13 was slightly higher than that of WT enzyme. The structural and molecular dynamics analysis revealed that the increase in hydrogen bonding and hydrophobic interaction in ASR A13 was the main factor responsible for maintaining the stability of the enzyme's molecular structure at high temperatures. The results showed that ASR strategy could modify DAEases to enhance the stability, activity or hybridity, which could provide superior biocatalyst sources for various industrial applications of functional sugars.

In order to improve the economic value of Panax quinquefolius L., this study used Panax quinquefolius L. as raw material to solid state ferment Panax quinquefolius L. by Schizophyllum commune, increased the content of active components in Panax quinquefolius L., and optimized the fermentation technology. In this study, the total ginsenoside content of Panax quinquefolius L. was used as the indicator. First, strain 2 was selected from three strains of Streptomyces as the solid state fermentation strain for Panax quinquefolius L.. Then single factor experiment was conducted on four factors affecting total ginsenoside content. The four factors included: fermentation temperature, inoculation amount of Schizophyllum commune, pH value and fermentation time. On the basis of these results, the technology of solid state fermentation of Panax quinquefolius L. by Schizophyllum commune was further optimized by response surface Box Behnken experimental design. The optimized process conditions were determined as follows: inoculation amount of Schizophyllum commune 10.90%, fermentation temperature 31 ℃, fermentation time 10 d, pH value 5.9. Under the above conditions, the total ginsenoside content of Panax quinquefolius L. fermented by Schizophyllum commune was 10.28%, the content of crude polysaccharide was 12.85%, and the content of total flavonoids was 0.67%, which were higher than that of unfermented Panax quinquefolius L., and the contents of macromolecules ginsenoside Rb1, Rg2 and Re decreased, while the contents of micromolecules ginsenoside Rg1, Rc, Rb2, Rd, Rg3, s-Rh2, r-Rh2 and pseudo-ginsenoside CK increased. Among them, rare ginsenoside Rg3, s-Rh2, r-Rh2, and pseudo-ginsenoside CK were new saponins. In vitro antioxidant tests showed that the IC50 values of DPPH and ABTS+ free radicals scavenging ability of the fermented products of Panax quinquefolius L. by Schizophyllum commune were 3165 and 10910 μg/mL, respectively, which were stronger than those of unfermented Panax quinquefolius L.. This study proved that the solid state fermentation of Panax quinquefolius L. by Schizophyllum commune increased the contents of total ginsenoside, crude polysaccharide, total flavone and rare ginsenoside, and enhanced the antioxidant capacity, which provided data support for the development and utilization of Panax quinquefolius L..

Goal: Contractile response and calcium handling are central to understanding cardiac function and physiology, yet existing methods of analysis to quantify these metrics are often time-consuming, prone to mistakes, or require specialized equipment/license. We developed BeatProfiler, a suite of cardiac analysis tools designed to quantify contractile function, calcium handling, and force generation for multiple in vitro cardiac models and apply downstream machine learning methods for deep phenotyping and classification. Methods: We first validate BeatProfiler's accuracy, robustness, and speed by benchmarking against existing tools with a fixed dataset. We further confirm its ability to robustly characterize disease and dose-dependent drug response. We then demonstrate that the data acquired by our automatic acquisition pipeline can be further harnessed for machine learning (ML) analysis to phenotype a disease model of restrictive cardiomyopathy and profile cardioactive drug functional response. To accurately classify between these biological signals, we apply feature-based ML and deep learning models (temporal convolutional-bidirectional long short-term memory model or TCN-BiLSTM). Results: Benchmarking against existing tools revealed that BeatProfiler detected and analyzed contraction and calcium signals better than existing tools through improved sensitivity in low signal data, reduction in false positives, and analysis speed increase by 7 to 50-fold. Of signals accurately detected by published methods (PMs), BeatProfiler's extracted features showed high correlations to PMs, confirming that it is reliable and consistent with PMs. The features extracted by BeatProfiler classified restrictive cardiomyopathy cardiomyocytes from isogenic healthy controls with 98% accuracy and identified relax90 as a top distinguishing feature in congruence with previous findings. We also show that our TCN-BiLSTM model was able to classify drug-free control and 4 cardiac drugs with different mechanisms of action at 96% accuracy. We further apply Grad-CAM on our convolution-based models to identify signature regions of perturbations by these drugs in calcium signals. Conclusions: We anticipate that the capabilities of BeatProfiler will help advance in vitro studies in cardiac biology through rapid phenotyping, revealing mechanisms underlying cardiac health and disease, and enabling objective classification of cardiac disease and responses to drugs.

Perilla (Perilla frutescens) seeds are emerging as a valuable resource for functional foods and medicines owing to their rich oil and protein content with diverse nutritional and health benefits. Perilla seed oil (PSO) possesses a high level of a-linolenic acid (ALA), a favorable ratio of unsaturated to saturated fatty acids, and other active ingredients such as tocopherols and phytosterols, which contribute to its antioxidant, anti-inflammatory, and cardiovascular protective effects. The balanced amino acid ratio and good functional properties of perilla seed protein make it suitable for a variety of food applications. The chemical composition, health benefits, and potential applications of PSO as well as the structural characterization, functional properties, modification methods, bioactivities, and application scenarios of perilla seed protein are comprehensively presented in this paper. Furthermore, the challenges as well as future prospects and research focus of PSO and perilla seed protein are discussed. The growing interest in plant-based diets and functional foods has made PSO and perilla seed protein promising ingredients for the development of novel foods and health products. The purpose of this paper is to highlight implications for future research and development utilizing these two untapped resources to improve human health and nutrition.

Acanthopanax senticosus (AS) is a geo-authentic crude medicinal plant that grows in China, Korea, Russia, and Japan. AS contains bioactive compounds such as eleutherosides, polysaccharides, and flavonoids. It is also a key traditional herb in the Red List of Chinese Species. AS is mainly distributed in Northeast China, specifically in Heilongjiang, Jilin, and Liaoning provinces. Its active compounds contribute to significant biological activities, including neuroprotective, antioxidant, anti-fatigue, and antitumor effects. However, the extraction methods of active compounds are complex, the extraction efficiency is poor, and the structure–activity relationship is unclear. This study focused on the nutrients in AS, including protein, carbohydrates, and lipids. Particularly, the active ingredients (eleutherosides, polysaccharides, and flavonoids) in AS and their extraction and purification methods were analyzed and summarized. The biological activities of extracts have been reviewed, and the mechanisms of anti-oxidation, antitumor, anti-inflammation, and other activities are introduced in detail. The applications of AS in various domains, such as health foods, medicines, and animal dietary supplements, are then reported. Compared with other extraction methods, ultrasonic or microwave extraction improves efficiency, yet they can damage structures. Challenges arise in the recovery of solvents and in achieving extraction efficiency when using green solvents, such as deep eutectic solvents. Improvements can be made by combining extraction methods and controlling conditions (power, temperature, and time). Bioactive molecules and related activities are exposited clearly. The applications of AS have not been widely popularized, and the corresponding functions require further development.

Perilla frutescens (L.) Britton is an annual herb plant of the Perilla genus in the Labiatae family, which is commonly utilized as an edible and medicinal resource. Polysaccharides are among the major components and essential bioactive compounds of P. frutescens, which exhibit a multitude of biological activities, including antioxidant, antitumor, anti-fatigue, immunoregulation, hepatoprotective, anti-inflammatory, and lipid-lowering effects. As a natural carbohydrate, P. frutescens polysaccharide has the potential to be utilized in the development of drugs and functional materials. In this paper, we provide an overview of progress made on the extraction, purification, structural characterization, and bioactivity of polysaccharides from different parts of P. frutescens. The challenges and opportunities for research are discussed, along with the potential development prospects and future areas of focus in the study of P. frutescens polysaccharides.

D-Allulose has become a promising alternative sweetener due to its unique properties of low caloric content, moderate sweetness, and physiological effects. D-Allulose 3-epimerase (DAEase) is a promising enzyme for D-Allulose production. However, the low catalytic efficiency limited its large-scale industrial applications. To obtain a more effective biocatalyst, a putative DAEase from Christensenellaceae bacterium (CbDAE) was identified and characterized. The recombinant CbDAE exhibited optimum activity at pH 7.5°C and 55°C, retaining more than 60% relative activity from 40°C to 70°C, and the catalytic activity could be significantly increased by Co2+ supplementation. These enzymatic properties of purified CbDAE were compared with other DAEases. CbDAE was also found to possess desirable thermal stability at 55°C with a half-life of 12.4 h. CbDAE performed the highest relative activity towards D-allulose and strong affinity for D-fructose but relatively low catalytic efficiency towards D-fructose. Based on the structure-guided design, the best double-mutation variant G36N/W112E was obtained which reached up to 4.21-fold enhancement of catalytic activity compared with wild-type (WT) CbDAE. The catalytic production of G36N/W112E with 500 g/L D-fructose was at a medium to a higher level among the DAEases in 3.5 h, reducing 40% catalytic reaction time compared to the WT CbDAE. In addition, the G36N/W112E variant was also applied in honey and apple juice for D-allulose conversion. Our research offers an extra biocatalyst for D-allulose production, and the comprehensive report of this enzyme makes it potentially interesting for industrial applications and will aid the development of industrial biocatalysts for D-allulose.

ObjectivePatients with pancreatic cancer (PC) have a poor prognosis. Radiotherapy (RT) is a standard palliative treatment in clinical practice, and there is no effective clinical prediction model to predict the prognosis of PC patients receiving radiotherapy. This study aimed to analyze PC’s clinical characteristics, find the factors affecting PC patients’ prognosis, and construct a visual Nomogram to predict overall survival (OS).MethodsSEER*Stat software was used to collect clinical data from the Surveillance, Epidemiology, and End Results (SEER) database of 3570 patients treated with RT. At the same time, the relevant clinical data of 115 patients were collected from the Affiliated Cancer Hospital of Zhengzhou University. The SEER database data were randomly divided into the training and internal validation cohorts in a 7:3 ratio, with all patients at The Affiliated Cancer Hospital of Zhengzhou University as the external validation cohort. The lasso regression was used to screen the relevant variables. All non-zero variables were included in the multivariate analysis. Multivariate Cox proportional risk regression analysis was used to determine the independent prognostic factors. The Kaplan-Meier(K-M) method was used to plot the survival curves for different treatments (surgery, RT, chemotherapy, and combination therapy) and calculate the median OS. The Nomogram was constructed to predict the survival rates at 1, 3, and 5 years, and the time-dependent receiver operating characteristic curves (ROC) were plotted with the calculated curves. Calculate the area under the curve (AUC), the Bootstrap method was used to plot the calibration curve, and the clinical efficacy of the prediction model was evaluated using decision curve analysis (DCA).ResultsThe median OS was 25.0, 18.0, 11.0, and 4.0 months in the surgery combined with chemoradiotherapy (SCRT), surgery combined with radiotherapy, chemoradiotherapy (CRT), and RT alone cohorts, respectively. Multivariate Cox regression analysis showed that age, N stage, M stage, chemotherapy, surgery, lymph node surgery, and Grade were independent prognostic factors for patients. Nomogram models were constructed to predict patients’ OS. 1-, 3-, and 5-year Time-dependent ROC curves were plotted, and AUC values were calculated. The results suggested that the AUCs were 0.77, 0.79, and 0.79 for the training cohort, 0.79, 0.82, and 0.81 for the internal validation cohort, and 0.73, 0.93, and 0.88 for the external validation cohort. The calibration curves Show that the model prediction probability is in high agreement with the actual observation probability, and the DCA curve shows a high net return.ConclusionSCRT significantly improves the OS of PC patients. We developed and validated a Nomogram to predict the OS of PC patients receiving RT.

In order to improve the economic value of industrial hemp, an active ingredient cannabinoid (CBD) with medicinal value from industrial hemp leaves was extracted by ionic liquid assisted ultrasonic method and the extraction process was optimized. In this study, [C8mim]NTF2 was selected as the best extraction solvent from 16 kinds of imidazole ionic liquids based on the yield of CBD. Then single factor experiment was conducted on six factors affecting the yield of CBD extraction by ionic liquid assisted ultrasonic method. The six factors included: Ultrasonic power, ultrasonic temperature, ultrasonic time, ethanol concentration, molar concentration of ionic liquid and liquid material ratio. And the ethanol concentration was 65%. The ionic liquid molar concentration was 0.3 mol/L (65% ethanol solution preparation). On the basis of these results, four significant factors (ultrasonic power, ultrasonic temperature, ultrasonic time and liquid material ratio) were screened out by Plackett-Burman experimental design. The extraction process was further optimized by response surface Box-Behnken experimental design. The optimum extraction process conditions of CBD significant factors were as follows: Ultrasonic power 280 W, ultrasonic temperature 50 ℃, ultrasonic time 62.5 min, liquid material ratio 25 mL/g. Under the above conditions, the yield of CBD extracted by ionic liquid [C8mim]NTF2 was 7.66%±0.2%, the yield of CBD extracted by methanol was 6.42%±0.3%, and the yield of CBD extracted by 65% ethanol solution was 5.81%±0.2%. The extraction ability of CBD was ionic liquid [C8mim]NTF2>methanol>65% ethanol solution. The CBD degradation experiment showed that the CBD degradation rate of ionic liquid [C8mim]NTF2 was 16.40%±0.3%, which was smaller than that of methanol (24.65%±0.6%) and 65% ethanol solution (32.88%±0.5%). The results showed that adding 65% ethanol solution into ionic liquid [C8mim]NTF2 could not only reduce the degradation rate of CBD, but also increase the yield of CBD. This study proved that ionic liquid was not only a protective agent for CBD, but also an excellent solvent for CBD extraction. The technology of extracting CBD by ionic liquid assisted ultrasonic method was developed, which provided data support for the development and utilization of industrial hemp CBD.

The cellular network coexisting with device-to-device (D2D) communications has been studied extensively. Reconfigurable intelligent surface (RIS) and non-orthogonal multiple access (NOMA) are promising technologies for the evolution of 5G, 6G and beyond. Besides, sparse code multiple access (SCMA) is considered suitable for next-generation wireless network in code-domain NOMA. In this paper, we consider the RIS-aided uplink SCMA cellular network simultaneously with D2D users. We formulate the optimization problem which aims to maximize the cellular sum-rate by jointly designing D2D users’ resource block (RB) association, the transmitted power for both cellular users and D2D users, and the phase shifts at the RIS. The power limitation and users’ communication requirements are considered. The problem is non-convex, and it is challenging to solve it directly. To handle this optimization problem, we propose an efficient iterative algorithm based on block coordinate descent (BCD) method. The original problem is decoupled into three subproblems to solve separately. Simulation results demonstrate that the proposed scheme can significantly improve the sum-rate performance over various schemes.

PurposeTo compare Whole-brain radiation therapy with simultaneous integrated boost (WBRT+SIB) to stereotactic radiosurgery (SRS)for non-small cell lung cancer (NSCLC)with brain metastases (BMs)in terms of overall survival (OS), intracranial progression-free-survival(iPFS), toxicity and objective response rate (ORR)MethodsA retrospective review was performed in our hospital of 90 patients diagnosed with NSCLC- BM who received either SRS (n = 48) or WBRT+SIB (n = 42) from January 2016 to January 2022. 76 (84.44%) patients received systemic drug therapy after radiotherapy, including chemotherapy(n=53), targeted therapy(n=40), immunotherapy(n=23), and anti-vascular drug therapy(n=45). OS and iPFS were estimated by the Kaplan-Meier method and compared using the log-rank test. Univariate and Multivariate analysis of the prognostic factors was performed using the Cox proportional hazard regression model.ResultsThe WBRT+SIB cohort had a longer median iPFS (20.0 versus (VS) 12.0 months, P = 0.0069) and a similar median OS (32.0 vs 28.0 months, P = 0.195) than the SRS cohort. Intracranial objective response rates in WBRT +SIB and SRS cohorts were 76.19% and 70.09%, respectively (P = 0.566). Disease control rates were 88.09% and 83.33%, respectively (P = 0.521). Multivariate analysis showed that WBRT+SIB is the only factor affecting iPFS(hazard ratio (HR):0.597 {95%confidence interval(CI):0.370-0.966}, P=0.035). Sex, Liver metastasis and Lymph node metastasis are risk factors for NSCLC-BM.ConclusionIn the context of systemic drug therapy, WBRT+SIB may have better intracranial local control than SRS in NSCLC-BM patients.

In order to provide a theoretical basis for the application of Acanthopanax senticosus leaves in probiotic fermented health products, the Acanthopanax senticosus leaves were used as raw materials, and the three kinds of lactic acid bacteria were used for fermentation, namely Lactobacillus acidophilus, Lactobacillus casei and Lactobacillus plantarum. After that，the changes in the content of bioactive compounds in Acanthopanax senticosus leaves fermented by lactic acid bacteria were studied, and the effect on antioxidant and inhibitory activity of hypoglycemic related enzymes in vitro were evaluated. The results showed that the fermentation abilities of the 3 strains were different. The fermentation of Lactobacillus plantarum and Lactobacillus acidophilus significantly increased the content of total flavonoids in Acanthopanax senticosus leaves (P

In recent years, high entropy alloys (HEA) receive extensive attention for their excellent mechanical performance. In this paper, the FeCoNiCrMn high-entropy alloy reinforced material is produced by laser powder bed fusion (LPBF). The excellent tensile performance can be achieved through many strengthening mechanisms, e.g., solution strengthening, dislocation strengthening, fine-grain refinement, and dispersion strengthening. The reinforced material with additive Fe-based metallic glass shows a yield strength of 675 MPa, 29.8% higher than FeCoNiCrMn (520 MPa), and an average hardness of 241.9 HV, 12.7% higher than FeCoNiCrMn (214.6 HV). Meanwhile, the plasticity of the reinforced material is maintained at a good level. In comparison with FeCoNiCrMn, the corrosion current density is reduced by 18.9%, and the corrosion resistance is significantly improved. The high strength and corrosion resistance are achieved by the addition of Fe-based metallic glass, which provides a feasible approach for the preparation of HEA with enhanced mechanical properties in the future.

Abstract Anaplasma species, which are distributed worldwide, are gram-negative obligate intracellular tick-borne bacteria that pose a threat to human and animal health. Haemaphysalis longicornis ticks play a vital role as vectors in the transmission of Anaplasma pathogens. However, the Anaplasma species carried by H. longicornis in China are yet to be characterized. In this study, 1074 H. longicornis specimens were collected from goats in four provinces of China from 2018 to 2019 and divided into 371 sample pools. All tick sample pools were examined for the presence of Anaplasma species via nested PCR amplification of 16S ribosomal RNA, major surface protein 4 (msp4), or citric acid synthase (gltA) genes, which were sequenced to determine the molecular and phylogenetic characteristics of the isolates. The overall Anaplasma spp-positive rate of H. longicornis was determined to be 26.68% (99/371). The percentage prevalence of A. phagocytophilum-like1, A. bovis, A. ovis, A. marginale, and A. capra were 1.08% (4/371), 13.21% (49/371), 13.21% (49/371), 1.35% (5/371), and 10.24% (38/371), respectively, and the co-infection rate of two or more types of Anaplasma was 6.47% (24/371). Phylogenetic analyses led to the classification of A. phagocytophilum into an A. phagocytophilum-like1 (Anaplasma sp. Japan) group. Anaplasma bovis sequences obtained in this study were 99.8–100% identical to those of an earlier strain isolated from a Chinese tick (GenBank accession no. KP314251). Anaplasma ovis sequences showed 99.3–99.6% identity to an A. ovis human strain identified from a Cypriot patient (GenBank accession no. FJ460443). Only one msp4 sequence of A. marginale was detected and was grouped with those of other A. marginale isolates, and these A. capra isolates obtained in this present study may be zoonotic. The detection and characterization of four Anaplasma species in H. longicornis in this study have added to the current knowledge of the parasite and provided data on multiple Anaplasma species with veterinary and medical significance from four provinces of China.

A realistic and visible dynamic simulation platform can significantly facilitate research on underwater robots. This paper uses the Unreal Engine to generate a scene that resembles real ocean environments, before building a visual dynamic simulation platform in conjunction with the Air-Sim system. On this basis, the trajectory tracking of a biomimetic robotic fish is simulated and assessed. More specifically, we propose a particle swarm optimization algorithm-based control strategy to optimize the discrete linear quadratic regulator controller for the trajectory tracking problem, as well as tracking and controlling discrete trajectories with misaligned time series through introducing a dynamic time warping algorithm. Simulation analyses of the biomimetic robotic fish following a straight line, a circular curve without mutation, and a four-leaf clover curve with mutation are carried out. The obtained results verify the feasibility and effectiveness of the proposed control strategy.

Background: Immunotherapy is recommended by the NCCN (National Comprehensive Cancer Network) guidelines as the standard second-line treatment for advanced esophageal squamous cell carcinoma (ESCC). Patients with advanced ESCC can benefit from immunotherapy, but the overall survival time (OS) is still not satisfactory. Therefore, it is of great importance to select effective prognostic indicators.Methods: A retrospective follow-up study was conducted from January 2018 to January 2020 among 44 patients with advanced ESCC treated with second-line immune checkpoint inhibitors (programmed death -1 blocking agents) in our hospital. The cutoff values of baseline lactate dehydrogenase (LDH), LDH level at week 8, serum albumin, hemoglobin, neutrophils, monocytes, and platelets were obtained by receiver operating characteristic (ROC) curves. The Kaplan-Meier method was used to analyze the relationship between LDH at baseline, LDH level at week 8, and LDH changes during treatment with progression-free survival (PFS) and OS time. The Cox proportional hazards model was used for univariate and multivariate analyses to determine the predictors of OS.Results: In univariate analysis, we found patients with lower baseline LDH levels (cutoff value: 200 U/L) had a better median PFS (8 months vs. 3 months; HR = 2.420, 95% CI: 1.178–4.971, p = 0.016) and OS (14 months vs. 6 months; HR = 3.637, 95% CI: 1.638–8.074, p = 0.004). The level of LDH at week 8 and the changes in LDH during treatment were not significantly associated with PFS or OS. The multivariate analyses showed that baseline LDH was an independent predictor of PFS (HR = 2.712, 95% CI: 1.147–6.409, p = 0.023) and OS (HR = 6.260, 95% CI: 2.320–16.888, p < 0.001), and the monocyte count (HR = 0.389, 95% CI: 0.162–0.934, p = 0.035) was significantly associated with OS.Conclusion: Serum LDH is a powerful independent factor for PFS and OS in advanced ESCC patients treated with anti-PD-1 therapy.

BackgroundWe aimed to explore the role of local ablative treatment (LAT) in metastatic esophageal squamous cell cancer (ESCC) patients who received chemotherapy and identify patients who will most likely benefit.MethodsWe analyzed data of metastatic ESCC patients from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016. The chi-square test was used to evaluate the unadjusted clinicopathological categorical variables between the two groups. Univariate and multivariate Cox regression analyses were conducted to identify independent prognostic factors of overall survival. Propensity score matching (PSM) was used to adjust the differences between the two groups.ResultsOverall, 720 metastatic ESCC patients treated with chemotherapy were analyzed in this study; 63.2% of patients (n = 455) received LAT, including radiotherapy (n = 444), primary site surgery (n = 12), or lymph node dissection (n = 27). Gender (HR = 1.220, 95% CI: 1.024–1.453, p = 0.026), bone metastases (HR = 1.559, 95% CI: 1.292–1.882, p < 0.001), and liver metastases (HR = 1.457, 95% CI: 1.237–1.716, p < 0.001) were independent prognostic factors in the entire population. However, LAT was not an independent prognostic factor. Further subgroup analyses showed that LAT improved OS from 8.0 months to 10.0 months in patients with metastases other than bone/liver (HR = 0.759, 95% CI: 0.600–0.961, p = 0.022). LAT was not a prognostic factor in patients with bone/liver metastases (HR = 0.995, 95% CI: 0.799–1.239, p = 0.961). After PSM, the median OS was 8.0 months (95% CI: 7.2–8.8 months) and patients who received LAT had a better OS than patients without LAT (HR = 0.796, 95% CI: 0.653–0.968, p = 0.023). Patients with metastases other than bone/liver could benefit from LAT compared with those with bone/liver metastases.ConclusionsOur study indicated that metastatic ESCC patients with metastases other than bone/liver could derive additional benefit from LAT with systemic chemotherapy.

Tannases are a family of esterases that catalyze the hydrolysis of ester and depside bonds present in hydrolyzable tannins to release gallic acid. Here, a novel tannase from Lachnospiraceae bacterium (TanALb) was characterized. The recombinant TanALb exhibited maximal activity at pH 7.0 and 50°C, and it maintained more than 70% relative activity from 30°C to 55°C. The activity of TanALb was enhanced by Mg2+ and Ca2+, and was dramatically reduced by Cu2+ and Mn2+. TanALb is capable of degrading esters of phenolic acids with long-chain alcohols, such as lauryl gallate as well as tannic acid. The Km value and catalytic efficiency (kcat /Km) of TanALb toward five substrates showed that tannic acid (TA) was the favorite substrate. Homology modeling and structural analysis indicated that TanALb contains an insertion loop (residues 341–450). Based on the moleculer docking and molecular dynamics (MD) simulation, this loop was observed as a flap-like lid to interact with bulk substrates such as tannic acid. TanALb is a novel bacterial tannase, and the characteristics of this enzyme make it potentially interesting for industrial use.

ObjectivesVarious blood inflammatory biomarkers were associated with treatment response and prognosis of non-small cell lung cancer (NSCLC) in previous studies. In this study, we retrospectively evaluated the prognostic role of pretreatment blood inflammatory biomarkers and epidermal growth factor receptor (EGFR) mutation status in stage IIIA/N2 NSCLC patients with trimodality therapy.MethodsCompletely resected stage IIIA/N2 NSCLC patients with adjuvant chemotherapy and postoperative radiotherapy (PORT) were assessed in this study. Cutoff values of blood inflammatory factors were calculated by the R package SurvivalROC of R software. SPSS Statistics software was used for survival analyses. Kaplan-Meier survival curve and log-rank test were used to compare the survival difference between every two groups. Univariate and multivariate analyses of predictive factors were performed by Cox proportional hazards regression model.ResultsThe univariate analysis showed that T stage (p=0.007), EGFR mutation status (p=0.043), lymphocyte-to-monocyte ratio (LMR) (p=0.067), and systemic immune-inflammation index (SII) (p=0.043) were significant prognostic factors of disease-free survival (DFS). In the multivariate analysis, T2 (HR=0. 885, 95% CI: 0.059-0.583, p=0.004), EGFR mutation-positive (HR=0.108, 95% CI: 0.023-0.498, p=0.004) and elevated pretreatment SII (HR=0.181, 95%CI: 0.046-0.709, p=0.014) were independently related to shorter DFS. High pretreatment neutrophil counts (HR=0.113, p=0.019) and high systemic inflammation response index (SIRI) (HR=0.123, p=0.025) were correlated with worse overall survival (OS) by the univariate analysis. In the multivariate analysis, only high pretreatment SIRI was an independent predictor for poorer OS (HR=0.025, 95% CI: 0.001-0.467, p=0.014).ConclusionsIn conclusion, we identified that high pretreatment SII and SIRI were unfavorable prognostic factors in stage IIIA/N2 NSCLC patients treated with surgery, adjuvant chemotherapy and PORT. Patients with high pretreatment SII, high pretreatment SIRI, T2, and EGFR mutation-positive may need more forceful adjuvant treatment. Further prospective studies with large-scale are needed to validate our results and identify the proper cut-off values and optimum adjuvant treatment for distinct patient population.

Background: Camrelizumab (SHR1210) is a high-affinity, humanized immunoglobulin programmed cell death 1 (PD-1) monoclonal antibody. It was developed by Jiangsu Hengrui Medicine Co. Ltd. and has been approved for relapsed or refractory classical Hodgkin lymphoma patients and hepatocellular carcinoma patients in China. Apatinib is an orally administered vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor and has been approved for advanced gastric adenocarcinoma or gastroesophageal junction adenocarcinoma in China. Camrelizumab alone and its combination with apatinib have been used in the treatment of various solid cancers.Methods: We searched Embase, PubMed, and other databases with the keyword “camrelizumab” or “SHR1210,” and evaluated the safety and efficacy data of the involved studies. Adverse events (AEs) mentioned in at least two studies were summarized, including any grade and grade ≥3 treatment-related AEs. Meanwhile, efficacy data were collected, such as overall response rate (ORR), disease control rate (DCR), duration of response, 6-month progression-free survival (PFS) rate, median PFS time, 12-month overall survival rate, and median overall survival time.Results: The major AEs of camrelizumab alone were reactive cutaneous capillary endothelial proliferation, fatigue, aspartate aminotransferase increase, proteinuria, pruritus, and alanine transaminase increase. The ORR and DCR were 20.2% (95% CI: 15.1–26.6%, p = 0.000, I2 = 70.360) and 45.8% (95% CI: 39.0–52.7%, p = 0.256, I2 = 58.661), respectively. In the three studies of combination therapy, two studies were combined with apatinib and one combined with chemotherapy. For these studies, common AEs were hypertension, platelet count decrease, nausea, proteinuria, aspartate aminotransferase increase, and white blood cell count decrease. The pooled ORR, DCR, and 6-month PFS rate were 41.8% (95% CI: 29.7–54.9%, p = 0.220, I2 = 86.265), 82.4% (95% CI: 75.9–87.4%, p = 0.000, I2 = 55.207), and 56.2% (95% CI: 35.8–74.6%, p = 0.559, I2 = 79.739), respectively.Conclusion: Camrelizumab and its combination are tolerable and appear to be efficient in treating numerous solid cancers. The combination therapy appears to have better efficacy with durable toxicity. However, these remain to be shown in future studies. Besides, baseline lactate dehydrogenase, programmed cell death ligand 1 (PD-L1) expression, tumor mutation burden, and the incidence of reactive cutaneous capillary endothelial proliferation may be efficacy predictors and need to be clarified in further studies.

Lipases catalyze the hydrolysis of fats and oils, and have been widely used in various industrial fields. However, bacterial lipases have a lower thermostability in industrial processes, which was a limiting factor in their industrial application. In this study, we obtained an improve variant of Pseudomonas fluorescens lipase (PFL) with enhanced thermostability using classical error-prone PCR. Wild-type PFL showed an optimal temperature and pH of 50°C and pH 7.5, respectively. Due to the low thermostability of PFL, a library containing over 3000 individual mutants as constructed using error-prone PCR. Screening for thermotolerance yielded the mutants L218P and P184C/M243C with Tm values of 62.5 and 66.0°C, which was 2.5 and 6°C higher than that of the WT, respectively. The combination of the two mutants (P184C/M243C/L218P) resulted in an approximately additive effect with a Tm value of 68.0°C. Although the increase of Tm was not substantial, the mutant also had dramatically increased methanol tolerance. Structural analysis revealed that the introduction of a disulfide bond between P184C and M243C and the substitution of Pro to reduce the flexibility of a loop increased the thermostability of PFL, which provides a theoretical foundation for improving the thermostability and methanol tolerance of lipase family I.1 to resist the harsh conditions of industrial processes.

The genus Anaplasma (Rickettsiales: Anaplasmataceae), which includes the species Anaplasma capra, Anaplasma bovis, Anaplasma ovis, and Anaplasma phagocytophilum, is responsible for a wide variety of infections in both human and veterinary health worldwide. Multiple infections with these four Anaplasma pathogens have been reported in many cases. We introduce a novel multiplex PCR for the simultaneous detection of A. capra, A. bovis, A. ovis, and A. phagocytophilum, based on species-specific primers against the groEL (A. capra and A. bovis), msp4 (A. ovis), and 16S rRNA (A. phagocytophilum) genes. To verify the specificity of the PCR reactions, we evaluated four sets of primers to analyze samples containing different blood pathogens. The sensitivity of the multiplex PCR was evaluated by amplifying 10-fold dilutions of total genomic DNA extracted from sheep blood infected with A. capra, A. bovis, A. ovis, or A. phagocytophilum. The reproducibility of the assay was evaluated by testing 10-fold dilutions of total genomic DNA extracted from sheep blood infected with these pathogens from 100 to 10–3 ng/μL per reaction in triplicate on three different days. A total of 175 field blood DNA samples were used to evaluate the reproducibility of multiplex PCR compared with the simplex PCRs. PCR primers used in this study were confirmed to be 100% species-specific using blood pathogens previously identified by other methods. The lower limit of detection of the multiplex PCR with good repeatability enabled the detection of A. capra, A. bovis, A. ovis and A. phagocytophilum at concentrations of 3 × 10–5, 5 × 10–7, 2 × 10–5, and 7 × 10–7 ng/μL, respectively. There was no significant difference between conventional and multiplex PCR protocols used to detect the four Anaplasma species (P > 0.05). The results of the multiplex PCR revealed that the A. capra groEL gene, the A. bovis groEL gene, the A. ovis msp4 gene, and the A. phagocytophilum 16S rRNA gene were reliable target genes for species identification in clinical isolates, being specific for each of the four target Anaplasma species. Our study provides an effective, sensitive, specific, and accurate tool for the rapid differential clinical diagnosis and epidemiological surveillance of Anaplasma pathogens in sheep and goats.

Esophageal cancer (EC) is one of the most common cancers with poor survival in the world. Nowadays, a generous number of clinical trials are underway on the use of immunotherapy in EC patients, especially the programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors. However, only a few patients could benefit from single-agent therapy. Others need combination therapies to enhance the response rate and survival. In this review, we focus on PD-1/PD-L1 inhibitors and its combination options in EC patients. We also summarized the potential predictive biomarkers for PD-1/PD-L1 inhibitors treatment.

Robot simultaneous localization and mapping (SLAM) is often required when robots are used to explore prior-unknown environment,e.g.,in rescue scenarios.Fog computing,an emerging computing mode could be used to enable faster,more accurate,speedier,and energy-saved robot SLAM.The framework of fog-enabled robot SLAM addressing was proposed,and challenges it faced were analyzed.Finally,technologies by real implementation of testbed were demonstrated.

Device caching has emerged as a promising solution to alleviate backhaul overload in future wireless networks with mixed cooperative and selfish devices. The behaviors of these devices actually represent the inherent social-network characteristics of their users, i.e., people treat each other differently according to the closeness of their social relationships. In this paper, the concept of social selfishness is adopted to capture the social characteristics in mobile device caching. Devices can be cooperative or be selfish in dynamic content sharing environments according to their social tie strengths, just like their users tend to cooperate with their friends and show selfishness to strangers. Based on social selfishness, a novel device caching game model is proposed to analyze the limited resource and privacy issues in a typical mobile caching scenario. Then, a local optimal caching algorithm with social selfishness (LOCASS) is developed to address these challenging problems. Analytical results show that LOCASS can approach Nash equilibrium of the game, and therefore, achieving the best caching strategy for mixed cooperative and selfish devices. Further, extensive simulation results show that LOCASS offers much better performance, in terms of average offloading ratio and resource utilization, than traditional random, Most-popular-content and Greedy caching algorithms. Besides, under LOCASS, devices with low degrees are most likely to store popular contents, while devices with high degrees are more willing to store those comparatively unpopular contents and fetch popular ones from their cooperative-devices.

Anaplasma capra is an emerging zoonotic tick-borne pathogen with a broad host range, including many mammals. Dogs have close physical interactions with humans and regular contact with the external environment. Moreover, they have been previously reported to be hosts of Anaplasma phagocytophilum, A. platys, A. ovis, and A. bovis. To confirm whether dogs are also hosts of A. capra, pathogen DNA was extracted from blood samples of 521 dogs, followed by PCR amplification of the citrate synthase (gltA) gene, heat shock protein (groEL) gene, and major surface protein 4 (msp4) gene of the A. capra. A total of 12.1% (63/521) of blood samples were shown to be A. capra-positive by PCR screening. No significant differences were observed between genders (P = 0.578) or types (P = 0.154) of dogs with A. capra infections. However, significantly higher A. capra infections occurred in dogs with regular contact with vegetation (P = 0.002), those aged over 10 years (P = 0.040), and during the summer season (P = 0.006). Phylogenetic analysis based on gltA, groEL, and msp4 sequences demonstrated that the isolates obtained in this study were clustered within the A. capra clade, and were distinct from other Anaplasma species. In conclusion, dogs were shown to be a host of the human pathogenic A. capra. Considering the affinity between dogs and humans and the zoonotic tick-borne nature of A. capra, dogs should be carefully monitored for the presence of A. capra.

Pulsed power technology, whereas the electrical energy stored in a relative long period is released in much shorter timescale, is an efficient method to create high energy density physics (HEDP) conditions in laboratory. Around the beginning of this century, China Academy of Engineering Physics (CAEP) began to build some experimental facilities for HEDP investigations, among which the Primary Test Stand (PTS), a multi-module pulsed power facility with a nominal current of 10 MA and a current rising time ∼90 ns, is an important achievement on the roadmap of the electro-magnetically driven inertial confinement fusion (ICF) researches. PTS is the first pulsed power facility beyond 10 TW in China. Therefore, all the technologies have to be demonstrated, and all the engineering issues have to be overcome. In this article, the research outline, key technologies and the preliminary HEDP experiments are reviewed. Prospects on HEDP research on PTS and pulsed power development for the next step are also discussed.

The scaling rate of carp is one of the most important factors restricting the automation and intelligence level of carp processing. In order to solve the shortcomings of the commonly-used manual detection, this paper aimed to study the potential of hyperspectral technology (400–1024.7 nm) in detecting the scaling rate of carp. The whole fish body was divided into three regions (belly, back, and tail) for analysis because spectral responses are different for different regions. Different preprocessing methods, including Savitzky–Golay (SG), first derivative (FD), multivariate scattering correction (MSC), and standard normal variate (SNV) were applied for spectrum pretreatment. Then, the successive projections algorithm (SPA), regression coefficient (RC), and two-dimensional correlation spectroscopy (2D-COS) were applied for selecting characteristic wavelengths (CWs), respectively. The partial least square regression (PLSR) models for scaling rate detection using full wavelengths (FWs) and CWs were established. According to the modeling results, FD-RC-PLSR, SNV-SPA-PLSR, and SNV-RC-PLSR were determined to be the optimal models for predicting the scaling rate in the back (the coefficient of determination in calibration set (RC2) = 96.23%, the coefficient of determination in prediction set (RP2) = 95.55%, root mean square error by calibration (RMSEC) = 6.20%, the root mean square error by prediction (RMSEP)= 7.54%, and the relative percent deviation (RPD) = 3.98), belly (RC2 = 93.44%, RP2 = 90.81%, RMSEC = 8.05%, RMSEP = 9.13%, and RPD = 3.07) and tail (RC2 = 95.34%, RP2 = 93.71%, RMSEC = 6.66%, RMSEP = 8.37%, and RPD = 3.42) regions, respectively. It can be seen that PLSR integrated with specific pretreatment and dimension reduction methods had great potential for scaling rate detection in different carp regions. These results confirmed the possibility of using hyperspectral technology in nondestructive and convenient detection of the scaling rate of carp.

Anaplasma capra is an emerging pathogen, which can infect ruminants and humans. This study was conducted to determine the occurrence of A. capra in the blood samples of sheep and goats in China. Using nested polymerase chain reaction (nested-PCR) targeting the gltA gene and conventional PCR targeting the heat shock protein (groEL) gene and the major surface protein4 gene (msp4), A. capra was detected in 129 (8.9%) of 1453 sheep and goat blood samples. The positive rate was higher in goats (9.4%, 89/943) than in sheep (7.8%, 40/510) (χ2 = 1.04, p > 0.05, df = 1). For sheep, A. capra was found in 17 sites from 2 provinces. The prevalence was 28.6% in sheep from Liaoning province, which was higher than in Henan Province (7.3%). For goats, A. capra was detected in 35 sites from 7 provinces. The prevalence varied from 0 to 19.4% in the goat sites examined. The prevalence rates were 19.4, 19.3, 10, 8.8, 6.8, 1.8, and 0% in goats from Guizhou province, Henan Province, Inner Mongolia Autonomous Region, Shanxi Province, Xinjiang Uygur Autonomous Region, Yunnan province, and Gansu province, respectively. Based on the analysis of the A. capra citrate synthase gene (gltA), two variants were identified. Variant I showed a high sequence similarity to the A. capra, which were previously reported in sheep, goats, Ixodes persulcatus, Haemaphysalis longicornis, Haemaphysalis qinghaiensis, and humans. Variant II was only found in Luoyang, Anyang, and Sanmengxia, of Henan province. To our knowledge, this is the first detection of this variant of A. capra in sheep and goat blood in China. Phylogenetic analysis based on groEL and msp4 genes showed that the Anaplasma sp. sequences clustered independently from A. capra and other Anaplasma species with high bootstrap values. We found A. capra DNA in sheep and goats in China, providing evidence that sheep and goats can be infected by A. capra. We also found that this zoonotic pathogen is widely distributed in China. This study provides information for assessing the public health risks for human anaplasmosis.

The study of hyperspectral imaging in tandem with spectral preprocessing and neural network techniques was conducted to realize Colla Corii Asini (CCA, E’jiao) adulteration discrimination. CCA was adulterated with pig skin gelatin (PSG) in the range of 5–95% (w/w) at 5% increments. Three methods were used to pretreat the original spectra, which are multiplicative scatter correction (MSC), Savitzky-Golay (SG) smoothing, and the combination of MSC and SG (MSC-SG). SPA was employed to select the characteristic wavelengths (CWs) to reduce the high dimension. Colour and texture features of CWs were extracted as input of prediction model. Two kinds of artificial neural network (ANN) with three spectral preprocessing methods were applied to establish the prediction models. The prediction model of generalized regression neural network (GRNN) in tandem with the MSC-SG preprocessed method presented satisfactory performance with the correct classification rate value of 92.5%. The results illustrated that the integration of preprocessing methods, hyperspectral imaging features, and ANN modeling had a great potential and feasibility for CCA adulteration discrimination.

For the identification of salmon adulteration with water injection, a nondestructive identification method based on hyperspectral images was proposed. The hyperspectral images of salmon fillets in visible and near-infrared ranges (390–1050 nm) were obtained with a system. The original hyperspectral data were processed through the principal-component analysis (PCA). According to the image quality and PCA parameters, a second principal-component (PC2) image was selected as the feature image, and the wavelengths corresponding to the local extremum values of feature image weighting coefficients were extracted as feature wavelengths, which were 454.9, 512.3, and 569.1 nm. On this basis, the color combined with spectra at feature wavelengths, texture combined with spectra at feature wavelengths, and color-texture combined with spectra at feature wavelengths were independently set as the input, for the modeling of salmon adulteration identification based on the self-organizing feature map (SOM) network. The distances between neighboring neurons and feature weights of the models were analyzed to realize the visualization of identification results. The results showed that the SOM-based model, with texture-color combined with fusion features of spectra at feature wavelengths as the input, was evaluated to possess the best performance and identification accuracy is as high as 96.7%.

We demonstrate theoretically and experimentally that complete light transmission can be realized using a photonic heterostructure containing a tunable dielectric layer inserted between two different truncated photonic crystals (PCs). A perfect tunneling state is produced within enlarged photonic band gap (PBG) of the heterostructure by varying the thickness of inserted dielectric layer and the transmittance of the tunneling state depends on the dielectric layer thickness. Additionally, the tunneling state frequency varies with inserted layer thickness but is always located within the small overlapped PBG of two PCs. Therefore, both a perfect tunneling state and an ultrawide PBG can be realized in these heterostructures. The experimental results showed good agreement with theoretical values.

Ti-6Al-4V alloys with different build orientations have been fabricated by selective laser melting (SLM). The corrosion behavior and mechanical properties have been studied. Investigation of microstructures were characterized by optical microscopy (OM), scanning electron microscopy (SEM), and X-ray diffraction (XRD) analysis. Electrochemical results show that the vertical sample and horizontal sample possess excellent corrosion resistance in the cross section and longitudinal section respectively, which can be attributed to the presence of less acicular α′ martensite and more β phase. Mechanical properties of all samples were determined by compression testing and hardness measurements. The compression strength (σc) and plastic deformation (εp) of the horizontal sample were higher than those of the vertical sample and the sample with building direction of 45°, because the molten pool boundaries (MPBs) play a significant role in the microscopic slipping at the loading SLM parts. In addition, the sample with building orientation of 45° achieved highest hardness. Therefore, distinct anisotropy due to different build orientations.

The impact of nutritional status on survival among elderly esophageal squamous cell carcinoma (ESCC) patients undergoing radiotherapy is unclear. In this study, we aimed at validating the performance of the geriatric nutritional risk index (GNRI) in predicting overall survival time in elderly ESCC patients with radiotherapy. A retrospective cohort study was conducted on 239 ESCC patients aged 60 and over admitted consecutively from January 2008 to November 2014 in the Department of Radiotherapy, Henan Tumor Hospital (Affiliated Tumor Hospital of Zhengzhou University), Zhengzhou, Henan, China. All patients were subjected to nutritional screening using GNRI, and were followed for the occurrence of lymphatic node metastasis, radiation complication and mortality. The Kaplan-Meier method with Log-rank test was used to estimate survival curves. Univariable Cox regression analysis was used to identify variables associated with overall survival time. Among the 239 patients, 184 patients (76.9%) took no nutritional risk, 32 patients (13.4%) took moderate risk of malnutrition, and 23 patients (9.7%) took a high risk of malnutrition. Univariable Cox regression showed that both high nutritional risk group and moderate nutritional risk group were significantly less likely to survive than no nutritional risk patients (hazard ratio (HR) = 1.688, 95% confidence interval (CI) = 1.019-2.798 for moderate risk group, and HR = 2.699, 95% CI = 1.512-4.819 for high risk group, respectively). The GNRI is an independent prognostic factor for overall survival time in elderly ESCC patients with radiotherapy. A GNRI ≤98 can be suggested as an indicator of surviving less.

Ultrafine resveratrol (u-Res) particles were prepared through the SAS process. The orthogonal method was used to optimize the factors of the SAS process. The size of u-Res reached 0.68 μm under the optimum conditions. The characterization of the u-Res particles was tested by many analysis methods. The chemical structure of Res was unaffected by the SAS process. The degree of crystallinity of the u-Res particles greatly reduced. The purity of the u-Res particles increased from 98.5% to 99.2% during the SAS process. The u-Res particles had greater saturation solubility and dissolution rate than the raw-Res (r-Res) particles. The radical scavenging activity and bioavailability of the u-Res in vivo were 1.9 times of the r-Res.