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Background and Objectives: Nucleic acid‐amplification testing (NAT) is used for screening blood donations/donors for blood‐borne viruses. We reviewed global viral NAT characteristics and NAT‐yield confirmatory testing used by blood operators. Materials and Methods: NAT characteristics and NAT‐yield confirmatory testing used during 2019 was surveyed internationally by the International Society of Blood Transfusion Working Party Transfusion‐Transmitted Infectious Diseases. Reported characteristics are presented herein. Results: NAT was mainly performed under government mandate. Human immunodeficiency virus (HIV), hepatitis C virus (HCV) and hepatitis B virus (HBV) NAT was performed on all donors and donation types, while selective testing was reported for West Nile virus, hepatitis E virus (HEV), and Zika virus. Individual donation NAT was used for HIV, HCV and HBV by ~50% of responders, while HEV was screened in mini‐pools by 83% of responders performing HEV NAT. Confirmatory testing for NAT‐yield samples was generally performed by NAT on a sample from the same donation or by NAT and serology on samples from the same donation and a follow‐up sample. Conclusion: In the last decade, there has been a trend towards use of smaller pool sizes or individual donation NAT. We captured characteristics of NAT internationally in 2019 and provide insights into confirmatory testing approaches used for NAT‐yields, potentially benefitting blood operators seeking to implement NAT. [ABSTRACT FROM AUTHOR]

Carbamoyl azide is a pivotal compound used in the transformation into urea and amines, as well as in nitrene insertion reactions. In this study, we present a pioneering method for synthesizing carbamoyl azide directly from acid redox active esters without the use of metals or oxidants. This approach demonstrates tolerance for various functional groups, enhancing its applicability. Furthermore, this technique facilitates late‐stage modifications of natural products and pharmaceuticals, thereby accelerating the development and identification of novel drug candidates. [ABSTRACT FROM AUTHOR]

Background and Objectives: Nucleic acid amplification testing (NAT), in blood services context, is used for the detection of viral and parasite nucleic acids to reduce transfusion‐transmitted infections. This project reviewed NAT for screening blood donations globally. Materials and Methods: A survey on NAT usage, developed by the International Society of Blood Transfusion Working Party on Transfusion‐transmitted Infectious Diseases (ISBT WP‐TTID), was distributed through ISBT WP‐TTID members. Data were analysed using descriptive statistics. Results: Forty‐three responses were received from 32 countries. Increased adoption of blood donation viral screening by NAT was observed over the past decade. NAT‐positive donations were detected for all viruses tested in 2019 (proportion of donations positive by NAT were 0.0099% for human immunodeficiency virus [HIV], 0.0063% for hepatitis C virus [HCV], 0.0247% for hepatitis B virus [HBV], 0.0323% for hepatitis E virus [HEV], 0.0014% for West Nile virus [WNV] and 0.00005% for Zika virus [ZIKV]). Globally, over 3100 NAT‐positive donations were identified as NAT yield or solely by NAT in 2019 and over 22,000 since the introduction of NAT, with HBV accounting for over half. NAT‐positivity rate was higher in first‐time donors for all viruses tested except WNV. During 2019, a small number of participants performed NAT for parasites (Trypanosoma cruzi, Babesia spp., Plasmodium spp.). Conclusion: This survey captures current use of blood donation NAT globally. There has been increased NAT usage over the last decade. It is clear that NAT contributes to improving blood transfusion safety globally; however, there is a need to overcome economic barriers for regions/countries not performing NAT. [ABSTRACT FROM AUTHOR]

The pharmacodynamics in patients with high body fat percentage might be similar to those in obese patients. This randomised controlled clinical trial observed the effects of rocuronium in patients with different percent body fats (PBFs). Fifty‐four patients who underwent elective urological or pelvic surgery under general anaesthesia at Shanghai General Hospital were included in the present study; 51 patients were included for data analysis. Patients with normal PBF (<25%) were given a single dose of rocuronium calculated based on total body weight (N‐TBW, control group). Patients with a higher PBF (≥25%) were given a single dose of rocuronium calculated based on total body weight (H‐TBW). Patients with higher PBF and rocuronium were dosed based on fat‐free mass (H‐FFM). A train of four (TOF)‐Watch acceleromyography monitor was used to measure the effects of the rocuronium. H‐TBW (91.9 ± 28.8 s) had significantly shorter onset time than N‐TBW and H‐FFM (p = 0.003). H‐TBW had significantly longer clinical duration time and pharmacological duration time than the other groups (p = 0.000 and 0.000, respectively); the TOF ratio0.25–0.9 time was significantly different among the three groups (p = 0.005). There were no significant differences in the recovery time (p = 0.103) or recovery index (p = 0.159) among the three groups. The effects of rocuronium dosed based on FFM in patients with high PBFs are similar to those in normal patients. A single dose of rocuronium calculated based on TBW might shorten the onset time, prolong the clinical and pharmacological duration times, and prolong the recovery time. [ABSTRACT FROM AUTHOR]

Ischemic stroke is one of the leading causes of death and disability among adults worldwide. Intravenous thrombolysis is the only approved pharmacological treatment for acute ischemic stroke. However, reperfusion by thrombolysis will lead to the rapid activation of microglia cells which induces interferon‐inflammatory response in the ischemic brain tissues. Panax quinquefolium saponins (PQS) has been proven to be effective in acute ischemic stroke, but there is no unified understanding about its specific mechanism. Here, we will report for the first time that PQS can significantly inhibit the activation of microglia cells in cerebral of MCAO rats via activation of Nrf2/miR‐103‐3p/TANK axis. Our results showed that PQS can directly bind to Nrf2 protein and inhibit its ubiquitination, which result in the indirectly enhancing the expression of TANK protein via transcriptional regulation on miR‐103‐3p, and finally to suppress the nuclear factor kappa‐B dominated rapid activation of microglial cells induced by oxygen–glucose deprivation/reoxygenation vitro and cerebral ischemia‐reperfusion injury in vivo. In conclusion, our study not only revealed the new mechanism of PQS in protecting against the inflammatory activation of microglia cells caused by cerebral ischemia‐reperfusion injury, but also suggested that Nrf2 is a potential target for development of new drugs of ischemic stroke. More importantly, our study also reminded that miR‐103‐3p might be used as a prognostic biomarker for patients with ischemic stroke. [ABSTRACT FROM AUTHOR]

Uric acid nephropathy (UAN) is caused by purine metabolism disorders. UAN rat models were established in SD rats. The modeling rats received different doses of hispidulin (10, 20, 50 mg/mL). Febuxostat was applied as the positive drug. Serum creatinine, uric acid (UA), and cystatin‐C (cys‐C), neutrophil gelatinase‐associated lipocalin (NGAL), IL‐1β, IL‐8, TNF‐α, and IL‐6 in rats were detected. HE staining was done to assess kidney injury. UAN rats possessed prominent levels of serum creatinine, UA, cys‐C, and NGAL, which all reduced after hispidulin treatment in a dose‐dependent manner. HE staining determined the improvement of kidney injury after treatment, which was comparable to the efficacy of febuxostat. Hispidulin inhibited the release of IL‐1β, IL‐8, TNF‐α, and IL‐6 in UAN rats. Hispidulin enhanced autophagy in UAN rats, presenting as ascending LC3II/I ratio and downregulated P62. The increasing trend of inflammasome‐related proteins of NLRP3 and Caspase‐1 was changeovered by hispidulin. The activation of NF‐kB signaling was intercepted by hispidulin in UAN rats. Hispidulin can effectively improve renal function injury caused by UAN in rats. The mechanism may be related to the inhibition of inflammatory response induced by autophagy and activation of NF‐κB pathway. [ABSTRACT FROM AUTHOR]

Background: Kidney renal clear cell carcinoma (KIRC) is a prevalent type of urological malignancy. The present study aimed to predict biomarkers for KIRC. Methods: We collected transcriptomic and clinical information for KIRC from The Cancer Genome Atlas and GSE22541 cohorts. Results: Unsupervised clustering of 35 epithelial–mesenchymal transformation (EMT)‐related differentially expressed gene profiles divided samples into two clusters with distinct immune characteristics. Six genes (IL20RB, DDC, ANKRD36BP2, F2RL1, TEK, and AMN) were found to construct a prognostic risk model using multivariate Cox regression analysis. Kaplan–Meier analysis suggested the better prognosis of the KIRC patients in the low‐risk group than that in the high‐risk group. Immune infiltration analyses was conducted using xCell and single‐sample gene set enrichment analysis, indicating that the risk score was associated with the immune microenvironment of the KIRC. Prognostic marker gene‐targeted medications with high drug sensitivity were predicted in KIRC patients. Conclusions: In summary, the present study identified IL20RB, DDC, ANKRD36BP2, F2RL1, TEK, and AMN as prognostic biomarkers, providing insight into immunotherapy and gene‐targeted drugs of KIRC. [ABSTRACT FROM AUTHOR]

The pelvic structure is complex and the tumor is poorly defined from the surrounding tissues. Finding the exact tumor resection margin based on the surgeon's clinical experience alone is a time‐consuming and difficult task, which is a major factor leading to surgical failure. An accurate method for segmenting pelvic bone tumors is needed. In this paper, a semiautomatic segmentation method for pelvic bone tumors based on CT‐MR multimodal images is presented. The method combines multiple medical prior knowledge and image segmentation algorithms. Finally, the segmentation results are visualized in three dimensions. We tested the proposed method on a collection of 10 cases (97 tumor MR images in total). The segmentation results were compared with the manual annotation of the physicians. On average, our method has an accuracy of 0.9358, a recall of 0.9278, an IOU value of 0.8697, a Dice value of 0.9280, and an AUC value of 0.9632. The average error of the 3D model was within the allowable range of the surgery. The proposed algorithm can accurately segment bone tumors in pelvic MR images regardless of tumor location, size, and other factors. It provides the possibility to assist pelvic bone tumor preservation surgery. [ABSTRACT FROM AUTHOR]

Metal–organic rotaxane compounds (MORCs) with supramolecular (pseudo)rotaxane motifs as main structures have inherent dynamic character, but their potential as responsive molecular machines is largely hampered by poor responsiveness to external stimuli. In this study, using a multi‐functionalized pseudorotaxane linker that combines two kinds of functionalities, a novel MORC, U‐bpybc‐CB8 (U refers to uranyl, bpybc refers to 1, 1'‐bis(4‐carboxybenzyl)‐4, 4'‐bipyridinium, and CB8 is cucurbit[8]uril), with multi‐responsive capability that can respond to both light and thermal stimuli, is reported. The characterization, combining spectra measurements and single‐crystal X‐ray diffraction, shows that, due to the involvement of viologen‐functionalized flexible organic dicarboxylate guest molecule in the CB8‐ involved pseudorotaxane ligand, the resultant uranyl‐based MORC exhibits photochromic behavior after UV or visible light irradiation. More interestingly, it is revealed that the exceptional thermal response of U‐bpybc‐CB8 as temperature increases from 170 to 270 K, i.e., volume expansion followed by contraction after the inflection temperature of ≈230 K, can be stemmed from the lattice flexibility of this metal–organic supramolecular network. The dual responsiveness of MORCs reported here demonstrates the potential of such supramolecular assemblies as smart molecular components like sensors and switches that respond to light irradiation or temperature changes. [ABSTRACT FROM AUTHOR]

The emerging visualization techniques have aroused wide interest for optical information detection and storage. However, they suffer from fairly limited optical information density and poor visual detection performance. Herein, an innovative surface patterning enhanced visualization (SPEV) approach is developed for ultrasensitive naked‐eye detection and RGB‐based high‐density information storage. Through "ship covalently linked in bottle" method, a novel HP‐UiO‐66‐NH2‐based ratiometric fluorescent (RF) composite probe is fabricated, exhibiting remarkably enhanced CdTe QDs encapsulation efficiency and superior dual‐sensing performance for F− and alkaline phosphatase (ALP). Then, the novel surface patterned CdTe QDs@HP‐UiO‐66‐NH2 hydrogel sensor is prepared, emitting multi‐stimuli‐responsive optical information with significantly improved abundance and dimensionality. The pseudo‐color postprocessing of the fluorescence images is performed to convert the analyte‐induced imperceptible color variations into easily perceptible color tonality change, resulting in ultra‐high sensitivity and excellent accuracy for naked‐eye quantitative detection of ALP and F− in human serum. Furthermore, the highly accurate pattern block‐based RGB (PB‐RGB) assay is demonstrated and the concept of RGB‐based 3D patterning codes is presented for highly reliable extraction of quantitative color information and high‐density information storage. The SPEV technique provides a universal route to realize instrument‐free precise visual quantitative detection, high‐density optical information storage, multi‐stimuli‐responsive encryption, and anti‐counterfeiting. [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess malnutrition using the Global Leadership Initiative on Malnutrition (GLIM) criteria and Subjective Global Assessment (SGA) at baseline and determine the GLIM criteria that best predicted unplanned hospitalization in outpatients with unintentional weight loss (UWL). Methods: We performed a retrospective cohort study of 257 adult outpatients with UWL. The GLIM criteria and SGA agreement were reported using the Cohen kappa coefficient. Kaplan‐Meier survival curves and adjusted Cox regression analyses were used for survival data. Logistic regression was used for the other correlation analysis. Results: This study collected data from 257 patients for 2 years. Based on the GLIM criteria and SGA, malnutrition prevalence was 79.0% and 72.0%, respectively (κ = 0.728, P < 0.001). Using the SGA as a standard, GLIM had a sensitivity of 97.8%, a specificity of 69.4%, a positive predictive value of 89.2%, and a negative predictive value of 92.6%. Malnutrition was associated with higher rates of unplanned hospital admission independent of other prognostic factors (GLIM: hazard ratio [HR]=2.85, 95% CI=1.22–6.68; SGA: HR=2.07, 95% CI=1.13–3.79). Of the five GLIM criteria–related diagnostic combinations, disease burden or inflammation was the most important to predict unplanned hospital admission in multivariable analysis (HR=3.27, 95% CI=2.03–5.28). Conclusion: There was good agreement between the GLIM criteria and the SGA. GLIM‐defined malnutrition, as well as all five GLIM criteria–related diagnosis combinations, had the potential to predict unplanned hospital admissions in outpatients with UWL within 2 years. [ABSTRACT FROM AUTHOR]

Objective: The impact of selenium (Se) on human thyroid function remains unclear, with inconsistent results from recent epidemiological studies. Moreover, the observed associations are prone to bias due to potential confounding and reverse causation. Mendelian randomization (MR) analysis facilitates the large minimization of biases produced by environmental and lifestyle influences, providing unconfounded estimates of causal effects using instrumental variables. We aim to examine the association between Se concentrations and human thyroid function using a two‐sample MR analysis. Design and Methods: Genetic instruments for Se concentrations, including toenail and blood (TAB) and blood Se concentrations, were identified from a genome‐wide association study (GWAS) of blood Se (n = 5477) and toenail Se levels (n = 4162). GWAS summary statistics on thyroid phenotypes were downloaded from the ThyroidOmics consortium, including thyroid‐stimulating hormone (TSH) (n = 54,288), free thyroxin (FT4) (n = 49,269), hypo (n = 53,423), and hyperthyroidism (n = 51,823). The MR study was conducted using the inverse‐variance weighted (IVW) method, supplemented with the weighted median and the mode‐based method. Results: Genetically determined TAB Se was negatively associated with FT4 (β = −.067; 95% confidence interval [CI] = −0.106, −0.028; p = 0.001) using the IVW analyses, as well in the additional analyses using the weighted median and weighted‐mode methods. No evidence in heterogeneity, pleiotropy or outlier single‐nucleotide polymorphisms was detected (all p > 0.05). Suggestive casual association between increased genetically determined TAB Se concentrations and decreased hypothyroidism risk was found by the IVW method (odds ratio [OR] = 0.847; 95% CI = 0.728, 0.985; p = 0.031). The causal effect of TAB Se on FT4 was observed in women (β = −.076; 95% CI = −0.129, −0.024; p = 0.004). However, the influence of genetically determined higher Se concentrations on TSH levels and hyperthyroidism revealed insignificance in the primary and sensitivity analyses. Conclusions: The present MR study indicated that high Se concentration enable the decreasing of FT4 levels, and the effects of Se concentrations on FT4 remain sex‐specific. [ABSTRACT FROM AUTHOR]

Given the prevalence of low‐pathogenic but highly infectious Omicron variants, a cohort study was conducted to assess the response and duration of novel coronavirus‐inactivated vaccine‐induced antibodies 1 year after the third dose (Day 641). Blood samples were collected and anti‐spike neutralizing antibodies (neutralizing antibody), total antibodies against the receptor‐binding domain of the spike protein (total antibody), and immunoglobulin G antibodies against the spike protein (IgG antibody) were determined. Antibody kinetics and attenuation were evaluated. The results showed that the levels of neutralizing, total, and IgG antibodies on Day 641 were 98.05 IU/mL, 152.8 AU/mL, and 7.68 S/CO, respectively. Levels of anti‐SARS‐CoV‐2 antibodies were higher in the younger subgroup than in the older subgroup at several time points after the second and third doses. The seropositive rate of neutralizing antibodies providing protection from infection or severe infection was 46.87% and 87.5%, and the seropositive rates of total antibody and IgG antibody were maintained at 100% and 90.63%, respectively. The half‐lives of neutralizing, total, and IgG antibodies were 186.89, 363.04, and 417.50 days, respectively. Collectively, anti‐SARS‐CoV‐2 antibodies may provide a certain degree of protection from infection 1 year after the third dose and high protection from severe infection. [ABSTRACT FROM AUTHOR]

BACKGROUND: In this study, a new crosslinking agent (CA) containing whey protein, papin, glycerin, and epigallocatechin gallate (EGCG), was prepared. The effects of CA content (0, 10, 20, 30, and 40%, v/v) on food packaging properties, crystallinity, microstructure, and antioxidant properties of pectin‐CA and chitosan‐CA composite films were analyzed. The results of this research offer a theoretical basis for engineering improved films for food packing. RESULTS: Pectin‐CA (30%) and chitosan‐CA (40%) composite films showed the best light transmission, water retention, breathability, plasticity, and antioxidant activity. Scanning electron microscopy revealed that these composite films exhibited a uniform and homogeneous structure without obvious pores. Fourier‐transform infrared spectroscopy (FTIR) and X‐ray diffraction (XRD) indicated that the amino acids and EGCG in CA were bonded to the film substrate (pectin/chitosan) via electrostatic interactions, hydrogen bonding, and covalent bonding, which led to an improvement in the film's properties. CONCLUSION: The CA has broad application prospects in food packaging as a cross‐linking agent and antioxidant. © 2022 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Background: Pathological angiogenesis is an important manifestation of syphilis, but the underlying mechanism of Treponema pallidum subspecies pallidum (T. pallidum)‐induced angiogenesis is poorly understood. Objectives: The objective of this study is to investigate the role and related mechanism of the T. pallidum membrane protein Tp47 in angiogenesis. Methods: The proangiogenic activity of recombinant T. pallidum membrane protein Tp47 in human umbilical vein endothelial cells (HUVECs) was assessed by tube formation assay, three‐dimensional angiogenesis analysis and experiments with a zebrafish embryo model. The effects of mitochondrial ROS and NADPH oxidase on intracellular ROS induced by Tp47 were further investigated. Furthermore, the levels of autophagy‐related proteins and autophagic flux were measured. Finally, the role of ROS‐induced autophagy in angiogenesis was studied. Results: Tp47 promoted tubule formation and the formation of angiogenic sprouts in vitro. In addition, a significant increase in the number of subintestinal vessel branch points in zebrafish injected with Tp47 was observed using a zebrafish embryo model. Tp47 also significantly increased intracellular ROS levels in a dose‐dependent manner. Tp47‐induced tube formation and angiogenic sprout formation were effectively prevented by the ROS inhibitor NAC. In addition, Tp47 enhanced the production of mitochondrial ROS and expression of the NADPH oxidase‐related proteins Nox2 and Nox4. The production of mitochondrial ROS and intracellular ROS was reduced by the NADPH oxidase inhibitors DPI and apocynin. Furthermore, Tp47 significantly increased expression of the autophagy‐related proteins P62 and Beclin 1 and the LC3‐II/LC3‐I ratio and promoted an increase in autophagic flux, which could be effectively rescued by coincubation with the ROS inhibitor NAC. Further intervention with the autophagy inhibitor BafA1 significantly inhibited tube formation and angiogenic sprout formation. Conclusions: Tp47‐induced NADPH oxidase enhanced intracellular ROS production via mitochondrial ROS and promoted angiogenesis through autophagy mediated by ROS. These findings may contribute to our understanding of pathological angiogenesis in syphilis. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is the leading cause of vision loss in working age population. Intravitreal injection of anti‐VEGF antibody is widely used in clinical practice. However, about 27% of patients show poor response to anti‐VEGF therapy and about 50% of these patients continue to have macular thickening. Frequent intravitreal injections of antibody may increase the chance of endophthalmitis and cause visual loss or even blindness once happened. Therefore, there is a greatly urgent need for novel noninvasive target to treat DR clinically. Here, the formulation of a smart supramolecular peptide (SSP) eye drop for DR treatment that is effective via specifically identifying and capturing soluble semaphorin 4D (sSema4D), a strongly pro‐angiogenesis and exudates factor, is reported. The SSP nanostructures encapsulate sSema4D so that all biological effects mediated by three receptors of sSema4D are inhibited, thereby significantly alleviating pathological retinal angiogenesis and exudates in DR. Moreover, it is found that combination of SSPs eye drop and anti‐VEGF injection shows better therapeutic effect over anti‐VEGF treatment alone. Overall, SSP eye drop provide an alternative and effective method for noninvasive treatment for DR. [ABSTRACT FROM AUTHOR]

Philadelphia chromosome‐positive acute myeloid leukemia (Ph + AML) is a rare type of AML with a low survival rate and poor prognosis. We first report a Ph + AML patient who remained in long‐term remission after the combination of flumatinib and venetoclax, which could provide corresponding treatment ideas for clinical practice. The figure shows the treatment process of the patient and the dynamic changes in blood cell count during venetoclax and flumatinib. The BCR::ABL1 transcript was negative after two courses of the combination of venetoclax anf flumatinib. No serious adverse events occurred during the treatment, although hematological toxicity was observed. [ABSTRACT FROM AUTHOR]

Soft matter catalyst system allowing controllable manipulation of the organized nanostructure and surface property holds the potential for renewable energy. Here we demonstrate the construction of a continuously regenerative hydrogel photocatalyst that confines the metal‐thiolate coordination induced nanocavity into robust micro‐sized spongy network for water splitting. Thanks to low vaporization enthalpy and fast proton mobility of water molecules confining in nanocavities, the composite delivers outstanding photocatalytic H2 production (TOF of 4568 H2 h−1), nearly 4.5 times higher than that on the catalyst without confinements. Incorporating with conductive polymers, the TOF is substantially improved to 7819 H2 h−1. Impressively, continuous regeneration is for the first time achieved with H2 production retention improved from 24 % to 72 % by regulating optically‐active catalyst surfaces. This optical regeneration method provides new avenues for sustainable solar energy conversion. [ABSTRACT FROM AUTHOR]

Background & Aims: The multiplicity of hepatocellular carcinoma (HCC) recurrence patterns is the most important determinant of patients' postsurgical survival. A systematic HCC recurrence classification is needed to help prevent and treat postoperative HCC recurrence in the era of precision medicine. Methods: A total of 1319 patients with recurrent HCC from four hospitals were enrolled and divided into a development cohort (n = 916), internal validation cohort (n = 225) and external validation cohort (n = 178). A comprehensive study of patients' clinicopathological factors and biological features was conducted. Results: Four subtypes of recurrence were identified, which integrated recurrence features, survival, effects on systemic and liver function and potential therapeutics after recurrence: type I (solitary‐intrahepatic oligorecurrence); type II (multi‐intrahepatic oligorecurrence); type III (progression recurrence) and type IV (hyper‐progression recurrence). Type III~IV recurrence indicated exceptionally poor prognosis. Subsequently, two nomogram models were established for type III~IV recurrence prediction, and both demonstrated excellent predictive performance and applicability of pre and postoperative strategy formulation. Multiple biological analyses revealed that HCC cases with type III~IV recurrence were characterized by enrichment in p53 mutations, CCND1 amplification, high proliferation/metastasis potential, inactive metabolism and immune exhaustion features. Over‐expression of high mobility group protein 2 (HMGA2) enhanced the highly malignant behaviour of HCC through multiple molecular pathways, making it a potential prognostic predictor and therapeutic target. Conclusions: This 'recurrent HCC classification' has important potential value in identifying patients with surgical benefit, predicting postsurgical survival and guiding treatment strategies. Multidimensional biological insights also increased knowledge of factors associated with HCC recurrence. [ABSTRACT FROM AUTHOR]

The role of organic aerosols (OA) as ice nucleating particles (INPs) deserves attention because of their high atmospheric abundance. The low concentration of INPs poses challenges in identifying the ice nucleation (IN) of OA among a mix of aerosol types in ambient environment. This study coupled a catalytic stripper system (350°C heating) with a continuous flow diffusion chamber to online investigate the immersion INPs of ambient particles at −30°C at a suburban site. Significant reduction (71 ± 25%) of INP concentrations after evaporation suggested that INPs can be significantly contributed by volatile OA. In addition, nonvolatile OA were more efficient INPs than black carbon. Oxygenated OA by photooxidation and lower ambient promoted the IN activity at noon, when the OA may be more viscous. These results hereby present the first field evidence that OA in anthropogenically influenced regions can be efficient INPs well above the homogeneous IN temperature. Plain Language Summary: Ice nucleating particles have an important impact on weather and climate by modulating cloud microphysics. Globally, measurements have demonstrated the ubiquitous presence of ice nucleating particles (INPs); however, the contribution of abundant organic aerosols (OA) to INPs remains uncertain owing to their complex compositions and varying phase states. In this study, using concurrent measurements between ambient and heated INPs, we prove the important contribution of volatile OA at 350°C to immersion freezing INPs at −30°C, especially at noon, when OA are more solid‐like because of their oxygenation by photooxidation and lower ambient relative humidity. In addition, nonvolatile OA were found to be a more efficient INPs than black carbon. Therefore, our results provide field evidence that OA in anthropogenically influenced regions could serve as an important atmospheric INPs at 8°C above the homogeneous freezing temperature. Key Points: Field measurements prove contribution of organic aerosols (OA) in anthropogenically influence region to immersion mode ice nucleation (IN)OA oxygenated by photooxidation and lower relative humidity showed a correlation with increased at noonNonvolatile OA at 350°C heating have a higher IN efficiency than that of black carbon [ABSTRACT FROM AUTHOR]

The Red River is located at the intersection of the Indian and East Asian monsoons. Understanding the evolution history of the monsoon in the Red River basin helps to comprehend the evolution of Asian Summer Monsoon. Herein, we present the high‐resolution major elements and Sr‐Nd isotopic ratios of the terrigenous sediment component for a well‐dated core retrieved from the northern South China Sea slope, aiming to identify the sediment provenance and reconstruct the silicate chemical weathering intensity since the past 36 kyr. The Red River was confirmed as the major sediment source through Sr‐Nd isotopic ratios. The silicate chemical weathering was affected by the rapid changes of sea level and monsoon, and thus it is difficult to indicate the regional paleoenvironment by the weathering degree. The principal component 1 composed of TFe2O3, Al2O3, K2O and MgO was shown to represent the fine‐grained sediment discharge, and employed as a proxy for the summer monsoon rainfall. Global cooling events/stages were identified through the proxies, including the Last Glacial Maximum, Heinrich events, Younger Dryas, and 8.2 ka, as well as the enhanced summer monsoon stages, including the Bølling/Allerød and early Holocene. Based on the comparison with the neighboring paleoclimate indicators, the region summer monsoon of the Red River basin was found to be governed by the Indian summer monsoon, and the summer insolation at low latitudes might be the primary forcing force on the orbital scale. Key Points: Silicate chemical weathering intensity in the Red River basin was controlled by sea level fluctuation, summer monsoon, and grain sizeElements (Fe, Al, K, Mg) concentrated in fine fraction were used for reconstructing the summer monsoon rainfall of the Red River basinThe regional summer monsoon of the Red River basin is forced by the summer insolation at low latitudes on the orbital scale [ABSTRACT FROM AUTHOR]

Background: We aimed to evaluate patients suitable for definitive radiation therapy (DRT) and liver local therapy (LLT) in addition to palliative chemotherapy (PCT) among those with de novo liver metastatic nasopharyngeal carcinoma (lmNPC). Methods: The overall survival (OS) and progression‐free survival (PFS) rates were calculated and compared in 610 patients with lmNPC. Results: Both the PCT+DRT and PCT+DRT+LLT groups had better survival outcomes than the PCT group. Among patients with complete response/partial response (CR/PR) after PCT, no significant differences in survival rates were observed between those treated with PCT+DRT and PCT+DRT+LLT (2‐year PFS: 27.0% vs. 32.9%, p = 0.263). Among patients with progressive disease/stable disease (PD/SD) after PCT, significantly better survival rates were observed in patients treated with PCT+DRT+LLT. Conclusions: DRT might benefit patients with lmNPC regardless of the tumor response after PCT. For patients with CR/PR, LLT might not be needed. For patients with PD/SD, LLT might improve survival outcomes. [ABSTRACT FROM AUTHOR]

Objectives: Establish a fetal heart anatomical cross-sectional database that correlates with screening transverse ultrasound images suggested by international professional organizations to detect congenital heart defects.Methods: Fetuses with suspected congenital heart defects identified using the following cardiac image sequences obtained from transverse slices beginning from the upper abdomen and ending in the upper thorax were the subjects of this study: (1) four-chamber view, (2) left ventricular outflow tract view, (3) three-vessel right ventricular outflow tract view, and (4) the three-vessel tracheal view. A database of digital two-dimensional images of the transverse sweep was created for fetuses with confirmed congenital heart defects. In addition, using four-dimensional ultrasound spatial-temporal image correlation, selected transverse ultrasound images were acquired as part of the database. Ultrasound-detected congenital heart defects were confirmed postnatally from pathological specimens of the heart and lungs using a cross-sectional technique that mirrored the ultrasound images described above. When anatomical specimens were not available, prenatal ultrasound-detected congenital heart defects were confirmed using postnatal echocardiography and/or following surgery.Results: The four screening views described in the Methods section identified 160 fetuses that comprised the database. Forty-five datasets consisted of both ultrasound and anatomical cross-sectional images. Thirteen percent (6/45) only had abnormalities of the four-chamber view (eg, endocardial cushion defects). Twenty-four percent (11/45) had abnormalities of the four-chamber view as well as right and left outflow tracts (eg, complex malformations). Of these, 10 of 11 had an abnormal tracheal view. Sixteen percent (7/45) had an abnormal four-chamber view and abnormal right outflow tract (eg, pulmonary stenosis). Thirty-three percent (15/45) had a normal four-chamber view but had abnormal right and left outflow tracts as well as an abnormal tracheal view (eg, tetralogy of Fallot, D-transposition of the great arteries).Conclusions: Combining both ultrasound and anatomical imaging may be of assistance in training imagers to recognize cardiovascular pathology when performing the screening examination of the fetal heart. [ABSTRACT FROM AUTHOR]

Medicinal phytochemicals, such as artemisinin and taxol, have impacted the world, and hypericin might do so if its availability issue could be addressed. Hypericin is the hallmark component of Saint John's wort (Hypericum perforatum L.), an approved depression alleviator documented in the US, European, and British pharmacopoeias with its additional effectiveness against diverse cancers and viruses. However, the academia‐to‐industry transition of hypericin remain hampered by its low in planta abundance, unfeasible bulk chemical synthesis, and unclear biosynthetic mechanism. Here, we present a strategy consisting of the hypericin‐structure‐centered modification and reorganization of microbial biosynthetic steps in the repurposed cells that have been tamed to enable the designed consecutive reactions to afford hypericin (43.1 mg L−1), without acquiring its biosynthetic knowledge in native plants. The study provides a synthetic biology route to hypericin and establishes a platform for biosustainable access to medicinal phytochemicals. [ABSTRACT FROM AUTHOR]

Background: To evaluate whether patients with post‐treatment metastasis are suitable for GP first‐line palliative chemotherapy (PCT) after undergoing GP IC. Methods: Seven hundred and forty‐six patients with post‐treatment metastasis after undergoing GP IC were eligible. Survival outcomes were compared. Results: Significant differences in survival rates were observed between patients treated with GP and non‐GP chemotherapy (2‐year progression‐free survival [PFS]: 0.7% vs. 9.7%). We investigated survival outcomes of patients treated with GP PCT within 2 years after undergoing GP IC, treated with GP PCT 2 years after undergoing GP IC, and those of non‐GP PCT patients (2‐year PFS: 0.0%, 2.3%, 9.7%). However, there was no difference in the 2‐year PFS between the patients that received GP PCT 2 years after undergoing GP IC and the non‐GP PCT treated patients. Conclusions: GP is not recommended for patients that have received GP IC within 2 years. Two years after undergoing GP IC, GP can be considered. [ABSTRACT FROM AUTHOR]

Background: To evaluate the prognostic value of the dynamic change in absolute lymphocyte counts (ALCs) and absolute monocyte counts (AMCs) and identify patients with N stage and plasma Epstein‐Barr virus (EBV) DNA levels in nasopharyngeal carcinoma (NPC) who are at risk of treatment failure. Methods: A total of 1124 eligible patients with Stage II–IVb NPC treated with concurrent chemoradiotherapy (CCRT) were enrolled. Percentage changes in the ALC (ΔALC%) and AMC (ΔAMC%) were calculated. Results: Patients with high ΔALC% were correlated with poorer 5‐year overall survival (OS), progression‐free survival (PFS), and distant metastasis‐free survival (DMFS) rates than those with low ΔALC%. Likewise, high ΔAMC% was significantly associated with worse outcome than low ΔAMC% (OS, p = 0.001; PFS, p = 0.001; DMFS, p = 0.034). Multivariate analyses revealed that ΔALC% (p = 0.046), ΔAMC% (p = 0.019), and EBV DNA level (p < 0.001) were independent prognostic factors for OS. With respect to PFS, ΔALC% (p = 0.036), ΔAMC% (p = 0.011), N classification (p = 0.016), and EBV DNA level (p < 0.001) were also independent prognosticators. Based on the aforementioned independent risk factors (ΔALC% ≥ 83.33%, ΔAMC% ≥ 40.00%, Stage N2–3, EBV DNA ≥ 4000 copies/ml), patients were divided into three different risk groups (low‐risk group [with <1 risk factor], intermediate risk group [with 1–3 risk factors], and high‐risk group [with 4 risk factors]) that correlated with disparate risks of death (p < 0.001), disease progression (p < 0.001), and distant metastasis (p < 0.001). Conclusions: High ΔALC% and ΔAMC% were correlated with poor prognosis in patients with NPC. Risk stratification based on ΔALC%, ΔAMC%, N classification, and plasma EBV DNA levels could provide potential utility for risk‐adapted therapeutic strategies for NPC. [ABSTRACT FROM AUTHOR]

Assemblies of nanoparticles possess extensive potentials for various applications due to their unique properties. These properties are significantly related to the morphology (size, shape) and spatial positioning of nanoparticles. To meet the needs of different application fields, it is important to tune the structures of assemblies in a controllable way. Currently, the morphology control and assembly of nanoparticles are generally conducted in two separate steps, which cannot resolve the contradiction between the need of sufficient surface charge for stabilizing nanoparticles and the necessity of overcoming the electrostatic repulsion during self‐assembly process. In this study, a simple one‐pot method to fabricate assembled gold nanoparticles (AuNPs) films with tunable morphologies is proposed. AuNPs are synthesized and self‐assembled simultaneously at cyclohexanone–water interface. The cyclohexanone in this system not only reduces the chloroauric acid solution to form AuNPs, but also establishes an oil–water interface with low interface energy, which can capture the AuNPs effectively for forming an ordered array. Furthermore, the morphologies of AuNPs are manipulated by simply tuning pH of the chloroauric acid solution. The fabricated AuNPs films with different morphologies are demonstrated to be applicable for surface enhanced Raman scattering detection, catalytic monitoring, and sensing. [ABSTRACT FROM AUTHOR]

The genus Flavivirus comprises numerous emerging and re‐emerging arboviruses causing human illness. Vaccines are the best approach to prevent flavivirus diseases. But pathogen diversities are always one of the major hindrances for timely development of new vaccines when confronting unpredicted flavivirus outbreaks. We used West Nile virus (WNV) as a model to develop a new live‐attenuated vaccine (LAV), WNV‐poly(A), by replacing 5ʹ portion (corresponding to SL and DB domains in WNV) of 3ʹ‐UTR with internal poly(A) tract. WNV‐poly(A) not only propagated efficiently in Vero cells, but also was highly attenuated in mouse model. A single‐dose vaccination elicited robust and long‐lasting immune responses, conferring full protection against WNV challenge. Such "poly(A)" vaccine strategy may be promising for wide application in the development of flavivirus LAVs because of its general target regions in flaviviruses. SYNOPSIS: West Nile virus (WNV) is one of the many members of the genus Flavivirus known to cause human diseases. Here we present a novel live attenuated WNV vaccine, WNV‐poly(A), that protects against WNV infections in a mouse model. WNV‐poly(A) was generated by replacing 5′ portion of 3′ UTR with internal poly(A) tract.WNV‐poly(A) propagate efficiently in Vero cells and is also highly attenuated in a mouse model.Internal poly(A) tract is stably maintained over multiple passages.Such poly(A) vaccine strategy may represent a universal approach to develop live attenuated flavivirus vaccines. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: The routine practices of examining submucosal lesions are not suitable for deep lesions. Therefore, we evaluated the efficacy of non‐real‐time image‐guided transnasal endoscopic fine‐needle aspiration biopsy (FNAB) in diagnosing nasopharyngeal carcinoma (NPC) with submucosal lesions. Study Design: The effectiveness evaluation of diagnostic methods. Methods: Fifty suspected NPC patients who failed in conventional biopsies were enrolled in this study. The efficacy, maneuverability, and safety of FNAB in diagnosing these intractable cases were evaluated. Results: The definitive diagnostic results of these 50 patients were NPC (34/50, 68.0%), nasopharyngeal necrosis (1/50, 2.0%), nasopharyngeal mucositis (12/50, 24.0%), and other cancers (3/50, 6.0%), respectively. The results of the diagnostic efficacy of FNAB were sensitivity, 89.2%; specificity, 100.0%; positive predictive value, 100.0%; negative predictive value, 76.5%; and accuracy, 92.0%, respectively. The area under the receiver operating characteristic curves was 0.946 (95% confidence interval = 0.884–1.00, P <.001). No severe complications occurred after FNAB. Conclusions: FNAB can improve the diagnostic efficiency of NPC occurring in the submucosal space. It can be an additional option for routine nasopharyngeal biopsy and is worthy of clinical application. Level of Evidence: 4 Laryngoscope, 131:1798–1804, 2021 [ABSTRACT FROM AUTHOR]

Compared to patients readmitted to general wards, readmitted patients in the intensive care unit (ICU) are exposed to higher mortality rates and prolonged hospital stays. Moreover, the readmission of ICU patients brings pressing challenges for ICU management. Most models are devoted to identifying the risk factors and developing classification models that can predict whether ICU patients will be readmitted. Though these models are prominent, they do not provide estimates for the frequency of readmissions. This paper establishes a prediction model, hybrid feature selection‐LightGBM (HFS‐LightGBM), to evaluate the probability and frequency of ICU patient readmissions empirically. In terms of feature selection, a hybrid feature selection (HFS) algorithm for LightGBM combines the filter and wrapper methods. Pearson's correlation coefficient is employed in the filter procedure. Then we adopt the targeted LightGBM classifier along with the recursive feature elimination and cross‐validated (RFECV) to produce the optimal feature subset. Additionally, the hyperparameters of the HFS‐LightGBM are optimized. The HFS‐LightGBM is employed on the real‐world ICU dataset containing 1722 patients' electronic health records. This model outperforms the current prevailing readmission models. The identified frequency can assist doctors in making specific interventions for patients to reduce the ICU readmission rate. [ABSTRACT FROM AUTHOR]

Chinese mahogany (Toona sinensis) is a woody plant that is widely cultivated in China and Malaysia. Toona sinensis is important economically, including as a nutritious food source, as material for traditional Chinese medicine and as a high‐quality hardwood. However, the absence of a reference genome has hindered in‐depth molecular and evolutionary studies of this plant. In this study, we report a high‐quality T. sinensis genome assembly, with scaffolds anchored to 28 chromosomes and a total assembled length of 596 Mb (contig N50 = 1.5 Mb and scaffold N50 = 21.5 Mb). A total of 34,345 genes were predicted in the genome after homology‐based and de novo annotation analyses. Evolutionary analysis showed that the genomes of T. sinensis and Populus trichocarpa diverged ~99.1–103.1 million years ago, and the T. sinensis genome underwent a recent genome‐wide duplication event at ~7.8 million years and one more ancient whole genome duplication event at ~71.5 million years. These results provide a high‐quality chromosome‐level reference genome for T. sinensis and confirm its evolutionary position at the genomic level. Such information will offer genomic resources to study the molecular mechanism of terpenoid biosynthesis and the formation of flavour compounds, which will further facilitate its molecular breeding. As the first chromosome‐level genome assembled in the family Meliaceae, it will provide unique insights into the evolution of members of the Meliaceae. [ABSTRACT FROM AUTHOR]

Autophagy is frequently induced in the hypoxic tumour microenvironment. Accumulating evidence reveals important functions of autophagy at the tumour‐immune interface. Herein, we propose an update on the roles of autophagy in modulating tumour immunity. Autophagy promotes adaptive resistance of established tumours to the cytotoxic effects of natural killer cells (NKs), macrophages and effector T cells. Increased autophagic flux in tumours dampen their immunogenicity and inhibits the expansion of cytotoxic T lymphocytes (CTLs) by suppressing the activation of STING type I interferon signalling (IFN‐I) innate immune sensing pathway. Autophagy in suppressive tumour‐infiltrating immune subsets maintains their survival through metabolic remodelling. On the other hand, autophagy is involved in the antigen processing and presentation process, which is essential for anti‐tumour immune responses. Genetic deletion of autophagy induces spontaneous tumours in some models. Thus, the role of autophagy is context‐dependent. In summary, our review has revealed the dichotomous roles of autophagy in modulating tumour immunity. Broad targeting of autophagy may not yield maximal benefits. The characterization of specific genes regulating tumour immunogenicity and innovation in targeted delivery of autophagy inhibitors into certain tumours are among the most urgent tasks to sensitize cold cancers to immunotherapy. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to select optimal candidates benefiting from the addition of induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) in stage II–IVa nasopharyngeal carcinoma (NPC) based on Epstein–Barr virus (EBV) DNA and nodal maximal standardized uptake values (SUVmax‐N) of [18F]‐fluorodeoxyglucose positron emission tomography. Patients and materials: A total of 679 patients diagnosed with stage II–IVa (except N0) NPC were retrospectively included in this study. Overall survival was the primary endpoint. Survival differences between different groups were compared using the log‐rank test. The hazard ratio (HR) and 95% confidence interval (CI) were calculated using a multivariable Cox proportional hazards model. Results: Both high levels of EBV DNA (>1500 copies/mL) and SUVmax‐N (>12.3) indicated worse survival conditions. All patients were divided into low‐ and high‐risk groups based on these two biomarkers. The risk group was an independent prognostic factor in OS, progression‐free survival (PFS), and distant metastasis‐free survival (DMFS) (all p‐values<0.05). The addition of IC to CCRT was associated with survival improvement in OS, PFS, and DMFS in high‐risk patients, while no survival difference was found between CCRT and IC+CCRT in low‐risk patients. Conclusions: Our study can help clinicians select stage II–IVa NPC patients who benefit from IC, which is important in guiding individual treatment. [ABSTRACT FROM AUTHOR]

Enantioconvergent hydrolysis by epoxide hydrolase is a promising method for the synthesis of important vicinal diols. However, the poor regioselectivity of the naturally occurring enzymes results in low enantioconvergence in the enzymatic hydrolysis of styrene oxides. Herein, modulated residue No. 263 was redesigned based on structural information and a smart variant library was constructed by site‐directed modification using an "optimized amino acid alphabet" to improve the regioselectivity of epoxide hydrolase from Vigna radiata (VrEH2). The regioselectivity coefficient (r) of variant M263Q for the R‐isomer of meta‐substituted styrene oxides was improved 40–63‐fold, and variant M263V also exhibited higher regioselectivity towards the R‐isomer of para‐substituted styrene oxides compared with the wild type, which resulted in improved enantioconvergence in hydrolysis of styrene oxide scaffolds. Structural insight showed the crucial role of residue No. 263 in modulating the substrate binding conformation by altering the binding surroundings. Furthermore, increased differences in the attacking distance between nucleophilic residue Asp101 and the two carbon atoms of the epoxide ring provided evidence for improved regioselectivity. Several high‐value vicinal diols were readily synthesized (>88% yield, 90%–98% ee) by enantioconvergent hydrolysis using the reprogrammed variants. These findings provide a successful strategy for enhancing the enantioconvergence of native epoxide hydrolases through key single‐site mutation and more powerful enzyme tools for the enantioconvergent hydrolysis of styrene oxide scaffolds into single (R)‐enantiomers of chiral vicinal diols. [ABSTRACT FROM AUTHOR]

Focus‐tunable lenses have found wide applications in optical communications, medical diagnostics, and consumer electronics. However, many focus‐tunable lenses have complex architecture, slow response, and low focal length variation, due principally to the separate design of optical path and activation mechanism and the use of liquid medium. Herein, a new self‐contained focus‐tunable lenses based on transparent and conductive gels are developed. The plano‐convex gels, acting both as lens and electrodes of actuator, with desirable curvature are precisely patterned by inkjet 3D printing. When a voltage is applied to the gel lenses, the elastomer membrane is stretched radially by Maxwell force, resulting in a reduction of lens thickness that corresponds to an increase of curvature radius. Therefore, a large focal length variation of 32–81% and a fast response speed of 80–153 ms are obtained. It is believed that this self‐contained focus‐tunable gel lenses can find many applications in portable optical devices, particularly suitable for space‐constrained tasks. [ABSTRACT FROM AUTHOR]

Introduction: Caragana jubata Poir (CJ) and Caragana changduensis Liou f. (CC) are the two main original plants of Lignum Caraganae (LIC, a clinically effective Tibetan materia medica) and the red heartwoods of CJ and CC have been used for the treatment of polycythemia, hypertension and menstrual disorders. Objective To establish a comprehensive method for rapid quality assessment of LIC based on revealing the characteristic components of LIC and to discriminate the plant sources and LIC from its adulterations. Methodology: A multi‐index and synthetically balanced orthogonal design L9 (34) experiment was performed to obtain an efficient ultrasonic extraction condition of LIC sample. High‐performance liquid chromatography coupled with an ultraviolet detector (HPLC‐UV) techniques were developed for fingerprinting and quantitative analysis of 14 major compounds in LIC, and the main components were identified by HPLC tandem mass spectrometry (HPLC‐MS/MS). HPLC fingerprint and chemometrics analysis were employed to visualise the distinction and relationship of LIC obtained from CJ and CC and to determine their potential characteristic markers. Results: Fourteen compounds including a new compound were identified and quantified in LIC. The potential characteristic markers in LIC were identified based on qualitative and fingerprint analysis. The hierarchical cluster analysis (HCA) and principle component analysis (PCA) showed obvious discrimination between LIC obtained from CJ and CC. Five batches of LIC samples were authenticated, and its adulterations were successfully found. Conclusion: A facile HPLC combined with fingerprint and chemometrics methods could rapidly evaluate the quality of LIC and discriminate LIC obtained from CJ and CC. 1. Fourteen chemical components in Lignum Caraganae were identified and quantified by HPLC‐MS/MS and HPLC‐UV analysis methods. 2. The analysis of HPLC fingerprint and chemometrics could discriminate the Lignum Caraganae from different plant sources and Lignum Caraganae from its adulterations. 3. A new compound, 6, 7, 2'‐trihydroxy‐4'‐methoxyisoflavanone was isolated and identified by spectral analysis. [ABSTRACT FROM AUTHOR]

In China, automated blood pressure monitors have been readily available for home use. Home blood pressure monitoring has been indispensable in the management of hypertension. There is therefore a need to establish guidelines for home blood pressure monitoring on the basis of the 2012 consensus document. In this guidelines document, the committee put forward recommendations on the selection and calibration of blood pressure measuring devices, the frequency (times) and duration (days) of blood pressure measurement, and the diagnostic threshold of home blood pressure. [ABSTRACT FROM AUTHOR]

Objective: We aimed to establish and validate two nomograms that predict progression‐free survival (PFS) and overall survival (OS) in patients with stage II–IVa nasopharyngeal carcinoma (NPC) while evaluating the benefit of concurrent chemotherapy. Patients and Methods: We randomly divided 3412 patients newly diagnosed with stage II‐IVa NPC between 2008 and 2013 into training and validation 'A' cohorts (n = 1706 each). Another set of patients diagnosed between 2014 and 2016 served as validation cohort 'B' (n = 1503). A Cox multivariate model using the backward stepwise approach was applied to develop the nomograms, which were assessed for accuracy (Harrel C index) and calibration. Results: The 3‐ and 5‐year PFS rates in the training cohort were 86.8% (95% confidence interval [CI] 85.0%‐88.6%) and 82.3% (95% CI 80.1%‐84.5%), respectively. For the PFS nomogram, 5 variables were selected based on a backward procedure in the multivariate Cox model (gender, T stage, N stage, Epstein‐Barr virus DNA, and treatment method). The same variables plus patient age and diabetes mellitus were used for the OS nomogram. The Harrell C indices of the training, validation A, and validation B cohorts were 0.711, 0.700, and 0.703, respectively, for PFS, and 0.775, 0.743, and 0.727, respectively, for OS. Both nomograms performed well in terms of calibration in the training and validation cohorts. Conclusions: Our nomograms are reliable prognostic predictors of PFS and OS in patients with stage II‐IVa NPC. These nomograms could robustly estimate an individual's benefit from concurrent chemotherapy, which assists in treatment decision‐making. [ABSTRACT FROM AUTHOR]

BACKGROUND: Discovery of novel insecticides and targets has received global attention in recent years. Ten genes coding for enzymes involved in the juvenile hormone biosynthetic pathway of Manduca sexta were studied as potential insecticide targets. RESULTS: We determined the expression of genes encoding some critical enzymes in the JH biosynthetic pathway. Farnesol dehydrogenase (FOLD), Juvenile hormone acid O‐methyltransferase (JHAMT) and Juvenile hormone epoxidase (CYP15C1) were selected as the candidate targets based on gene expression results. RNAi silencing and enzyme inhibitor tests were performed to validate whether these candidate genes could be the potential insecticide targets. The down‐regulation of FOLD, JHAMT and CYP15C1 resulted in a 68%, 82% and 79% reduction in the rates of JH biosynthesis in vitro, respectively. In addition, RNA interference and inhibitor studies of these enzymes following oral administration demonstrated the potential application in pest management, with respect to high mortality and effects on growth. CONCLUSION: Based on our study, FOLD, JHAMT and CYP15C1 could be potential targets for pest control as a consequence of their important roles in insect development. © 2019 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

The quantification of three alkaloids is important because quantitative study is a means of assessing the reliability of the experimental method, and three alkaloids of peimine, peiminine, and peimisine are main active ingredients in Chinese Pharmacopoeia 2015. An effective method based on the matrix solid‐phase dispersion microextraction was developed for the extraction of alkaloid compounds in Fritillariae Thunbergii Bulbus. Target analytes were analyzed by capillary electrophoresis coupled with quadrupole time‐of‐flight mass spectrometry. The optimized experimental condition was that 50 mg Fritillariae Thunbergii Bulbus was blended homogeneously with 10 mg citric acid for 5 min. Two hundred microliters of water acidized by 1 mol/L hydrochloric acid (pH = 4.5) was selected to elute tested alkaloids. The results demonstrated that the investigated method had low limits of detection (1.32–1.59 ng/mL), good recoveries (86.63–98.12%), and reproducibility (relative standard deviations of peak areas < 0.87%). The proposed matrix solid‐phase dispersion microextraction coupled with capillary electrophoresis combined with quadrupole time‐of‐flight mass spectrometry was successfully applied for the extraction of alkaloids in plants. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the prognostic value of combining pretreatment Epstein‐Barr virus (EBV) DNA level and cervical node necrosis (CNN) for patients with nasopharyngeal carcinoma (NPC) receiving intensity‐modulated radiotherapy (IMRT). A total of 607 incident nonmetastatic NPC patients treated with IMRT ± chemotherapy were reviewed. Patients were divided into four groups based on EBV DNA level and CNN status. The primary endpoint was progression‐free survival (PFS). Kaplan‐Meier curves with log‐rank test were applied to compare survival outcomes and the Cox proportional model was used to identify independent prognostic factors. Pretreatment EBV DNA level and CNN status were independent prognostic factors. Patients in the low‐level EBV DNA group or non‐CNN group had significantly better 5‐year PFS. Multivariate analyses demonstrated that CNN was an independent prognostic factor for overall survival (OS) (HR = 1.927, 95% CI: 1.129‐3.290, P = .016), PFS (HR = 1.492, 95% CI: 1.005‐2.214, P = .047), distant metastasis‐free survival (DMFS) (HR = 1.661, 95% CI: 1.044‐2.644, P = .032), but not locoregional relapse‐free survival. EBV DNA levels correlated significantly with CNN with a correlation coefficient of.324 (P < .001). Compared with low‐level EBV DNA and non‐CNN grouping, high‐level EBV DNA and CNN grouping had poor PFS. The combined classification was an independent prognostic factor for OS (P < .001), PFS (P = .001), and DMFS (P = .018). Pretreatment plasma EBV DNA level and CNN status both closely correlated with prognosis of NPC patients in the IMRT era. Combined EBV DNA level and CNN status improves risk stratification and prognostic value. [ABSTRACT FROM AUTHOR]

Introduction: The main active components in hawthorn leaves possess various biological activities such as anti‐inflammatory, antioxidant, and hypolipidemic effects. Therefore, it is necessary to develop an effective and reliable extraction method to extract these active compounds from hawthorn leaves. Objective: To establish a simple, rapid, and sensitive method for extraction and determination of polyphenolic compounds from hawthorn leaves. Methods: In this study, a microwave‐assisted reaction and extraction (MARE) combined with ultra‐high‐performance liquid chromatography with ultraviolet detector method was established to extract and determine the polyphenolic compounds in hawthorn leaves. The solid reagent aqueous solutions were applied as extraction solvents, preventing the use of organic solvents. The target analytes were identified by quadrupole time‐of‐flight tandem mass spectrometry. Several experimental parameters that can significantly affect the extraction efficiency were evaluated and optimised. Results: The optimal conditions were as follows: 0.1 g of sodium carbonate was used as solid reagent, the amount of sodium borate was set at 0.01 g, extraction time was 10 min, extraction temperature was set at 50°C, pH value was adjusted to 7. The validation experiments demonstrated that the method had high sensitivity with the limits of detection in the range 26.5–37.7 ng/mL. The average recoveries ranged from 80.22% to 93.27%. Conclusion: In this work, the proposed MARE method was successfully applied to extract and determine polyphenolic compounds in hawthorn leaf samples. Compared with other reported methods, the present method was faster, greener, and more sensitive. High extraction efficiencies and sensitivities of target compounds were achieved. The proposed method is a green, simple, easy operation, time‐saving and effective approach. [ABSTRACT FROM AUTHOR]