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Silkworm pupa peptide (SCP) was prepared by enzymatic hydrolysis and then chelated with soluble zinc ions to obtain silkworm pupa peptide-zinc chelates (SCP-Zn), so as to develop safe and easily absorbable zinc supplements and improve the utilization value of silkworm pupa. Taking the zinc chelating capacity as an index, the optimum preparation process of SCP-Zn was determined, and the structure of both SCP and SCP-Zn were characterized by ultraviolet spectrum, fluorescence spectra, scanning electron microscopy, elemental analysis, particle size analysis and Fourier transform infrared spectrum. The results showed that the chelation rate of silkworm chrysalis peptide was 58.05% under the conditions of 1% alkaline protease plus enzyme, pH8.0, temperature 50 ℃ and enzymatic hydrolysis time 6 h. The optimum preparation conditions for preparation of SCP-Zn nanoparticles were as follows: Mass ratio of zinc peptide 1:0.5, pH6.5, 55 ℃, time 20 min, and the chelation rate of zinc reached 72.63%. The results of ultraviolet spectrum and fluorescence spectrum showed that zinc ions successfully combined with SCP. The obtained chrysalis SCP-Zn belongs to nanoparticles with an average particle size of 71.99 nm, with uniform granular structure on the surface, and the relative content of zinc reached 37.46%. The -COOH, -NH2 and -C=O in the peptide chain were the main binding sites of Zn2+ and SCP. The results indicated that silkworm pupa was a good raw material for preparation of zinc chelates. The study provides a theoretical basis for enriching organic zinc supplement resources and the high value utilization of silkworm pupa.

IntroductionPlant height (PH) and ear height (EH) are key plant architectural traits in maize, which will affect the photosynthetic efficiency, high plant density tolerance, suitability for mechanical harvestingMethodsQTL mapping were conducted for PH and EH using a recombinant inbred line (RIL) population and two corresponding immortalized backcross (IB) populations obtained from crosses between the RIL population and the two parental lines.ResultsA total of 17 and 15 QTL were detected in the RIL and IB populations, respectively. Two QTL, qPH1-1 (qEH1-1) and qPH1-2 (qEH1-4) in the RIL, were simultaneously identified for PH and EH. Combing reported genome-wide association and cloned PH-related genes, co-expression network analyses were constructed, then five candidate genes with high confidence in major QTL were identified including Zm00001d011117 and Zm00001d011108, whose homologs have been confirmed to play a role in determining PH in maize and soybean.DiscussionQTL mapping used a immortalized backcross population is a new strategy. These identified genes in this study can provide new insights for improving the plant architecture in maize.

Abstract Background Retinoblastoma (RB) is the most common prevalent intraocular malignancy among infants and children, particularly in underdeveloped countries. With advancements in genomics and transcriptomics, noncoding RNAs have been increasingly utilized to investigate the molecular pathology of diverse diseases. Aims This study aims to establish the competing endogenous RNAs network associated with RB, analyse the function of mRNAs and lncRNAs, and finds the relevant regulatory network. Methods and Results This study establishes a network of competing endogenous RNAs by Spearman correlation analysis and prediction based on RB patients and healthy children. Enrichment analyzes based on Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes are conducted to analyze the potential biological functions of lncRNA and mRNA networks. Weighted gene co‐expression network analysis (WGCNA) is employed to identify gene cluster modules exhibiting the strongest correlation with RB. The results indicate a significant correlation between the lncRNA MIR17HG (R = .73, p = .02) and the RB phenotype. ceRNA networks reveal downstream miRNAs (hsa‐mir‐425‐5p and hsa‐mir455‐5p) and mRNAs (MDM2, IPO11, and ITGA1) associated with MIR17Hg. As an inhibitor of the p53 signaling pathway, MDM2 can suppress the development of RB. Conclusion In conclusion, lncRNAs play a role in RB, and the MIR17HG/hsa‐mir‐425‐5p/MDM2 pathway may contribute to RB development by inhibiting the p53 signaling pathway.

Purpose: The purpose of this study is to investigate the efficacy and safety of immune checkpoint inhibitors (ICIs) or plus with chemotherapy in older patients. Methods: We enrolled 110 older patients with non-small cell lung cancer (NSCLC ≥75 years) who received either chemotherapy alone (chemo), ICI plus chemotherapy (ICI + chemo), or ICI alone and ICI plus other therapies, which included anti-angiogenesis drugs or other novel ICI (ICIs). Patient characteristics, treatment response, survival, and toxicity were evaluated. Results: In total population, the ICIs group has the highest disease control rate (DCR 75%). There were no significant differences in progression-free survival (PFS) and overall survival (OS) among older patients between ICI + chemo and ICIs groups (PFS: 5.3 months vs. 5.5 months, p = 0.70, OS: 10.7 months vs. 20.3 months, p = 0.995). Meanwhile, we observed ICIs had a longer PFS and OS than chemo group (PFS: 3.9 months vs. 5.5 months, p = 0.01, OS: 10.9 months vs. 20.3 months, p = 0.05). Subgroup analysis showed that patients with programmed death ligand-1 (PD-L1) ≥ 1% had a distinct longer trend toward OS in ICIs group compared to ICI + chemo group (22.4 months vs. 10.7 months, p = 0.605), even though there was no significant difference. In terms of safety, ICIs was more tolerable and had a lower discontinuation rate than ICI + chemo group. Conclusion: In the real world, ICI + chemo is more likely to be discontinued due to adverse effects and does not significantly improve patient survival compared with ICIs treatment in total population and subgroup. Therefore, ICI alone or ICIs plus other therapies, such as anti-angiogenesis drugs or other novel ICI (ICIs) could be recommended for older cases with PD-L1 positive NSCLC.

The aim of this study was to investigate the effects of in vitro simulated digestion on the stability and structure of oyster protein hydrolysate zinc nanoparticles (OPH-Zn), and to reveal the dynamic variation rule of OPH-Zn under different degrees of gastrointestinal digestion. Atomic absorption spectrophotometer, UV scanner, infrared spectrometer, fluorescence spectrometer, scanning electron microscope, transmission electron microscope and particle size analyzer were used to determine the zinc content, surface morphology, secondary structure and molecular weight distribution of OPH-Zn in digestive fluid in simulated gastrointestinal digestion process. The results showed that the total zinc content of OPH-Zn was 228.89±2.53 mg/g. During simulated gastric digestion, soluble zinc content in OPH-Zn and ZnSO4 controls remained stable basically, and there was no significant difference between the two samples (P>0.05). When the digestion was transferred from the stomach to the intestine, the zinc solubility of OPH-Zn and ZnSO4 decreased by 28.07% and 55.31% (P

Abstract Background Lung Adenocarcinoma (LUAD) is a major component of lung cancer. Endoplasmic reticulum stress (ERS) has emerged as a new target for some tumor treatments. Methods The expression and clinical data of LUAD samples were downloaded from The Cancer Genome Atlas (TCGA) and The Gene Expression Omnibus (GEO) database, followed by acquiring ERS-related genes (ERSGs) from the GeneCards database. Differentially expressed endoplasmic reticulum stress-related genes (DE-ERSGs) were screened and used to construct a risk model by Cox regression analysis. Kaplan–Meier (K-M) curves and receiver operating characteristic (ROC) curves were plotted to determine the risk validity of the model. Moreover, enrichment analysis of differentially expressed genes (DEGs) between the high- and low- risk groups was conducted to investigate the functions related to the risk model. Furthermore, the differences in ERS status, vascular-related genes, tumor mutation burden (TMB), immunotherapy response, chemotherapy drug sensitivity and other indicators between the high- and low- risk groups were studied. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the mRNA expression levels of prognostic model genes. Results A total of 81 DE-ERSGs were identified in the TCGA-LUAD dataset, and a risk model, including HSPD1, PCSK9, GRIA1, MAOB, COL1A1, and CAV1, was constructed by Cox regression analysis. K-M and ROC analyses showed that the high-risk group had a low survival, and the Area Under Curve (AUC) of ROC curves of 1-, 3- and 5-years overall survival was all greater than 0.6. In addition, functional enrichment analysis suggested that the risk model was related to collagen and extracellular matrix. Furthermore, differential analysis showed vascular-related genes FLT1, TMB, neoantigen, PD-L1 protein (CD274), Tumor Immune Dysfunction and Exclusion (TIDE), and T cell exclusion score were significantly different between the high- and low-risk groups. Finally, qRT-PCR results showed that the mRNA expression levels of 6 prognostic genes were consistent with the analysis. Conclusion A novel ERS-related risk model, including HSPD1, PCSK9, GRIA1, MAOB, COL1A1, and CAV1, was developed and validated, which provided a theoretical basis and reference value for ERS-related fields in the study and treatment of LUAD.

Abstract Background Currently there is no standard therapy recommended for second‐line treatment for thymic carcinoma. Our study compared multidrug chemotherapy, single‐agent chemotherapy, and PD‐1 inhibitors in patients diagnosed with advanced thymic carcinoma who had previous platinum‐based chemotherapy at the clinic. Methods The study included patients with thymic carcinoma who failed first‐line platinum‐based chemotherapy. Kaplan–Meier methods were applied in the study for estimating the progression‐free survival (PFS) and overall survival (OS) curves. Pearson chi‐square or Fisher's exact chi‐square test was adopted to make comparisons of the objective response rate (ORR) between treatment groups. Cox regression was used for the multivariate analyses in PFS and OS. Results Among the 92 patients enrolled, multidrug chemotherapy was used in 51 (55.4%) patients for second‐line therapy. Thirty‐six patients (35.9%) received single‐agent chemotherapy, and eight patients (8.7%) underwent PD‐1 inhibitors. The multidrug chemotherapy group showed better efficacy than the other two groups, with an ORR of 35.3% (p = 0.006). The median PFS of multidrug chemotherapy, single‐agent chemotherapy and PD‐1 inhibitors were 5.0 months, 3.0 months, and 4.0 months, respectively (p = 0.008). Patients in the multidrug chemotherapy group also showed an advantage in OS in comparison with the other two treatment groups (p = 0.045), with a median OS of 30.4 months. Multivariate analysis showed that second‐line treatment was independent factor for both PFS (p = 0.035) and OS (p = 0.037). Grade 3–4 AEs were mostly detected in patients receiving multidrug chemotherapy and were primarily hematologic. Treatment‐related mortality was not found in any of the groups. Conclusions Multidrug chemotherapy had a trend toward a more positive response rate and outcomes in longer survival time than single‐agent chemotherapy and PD‐1 inhibitors. Multidrug chemotherapy is a choice worth considering for second‐line therapy in patients with thymic carcinoma if tolerable.

Describing the hydraulic conductivity of unsaturated soil is very important in predicting water transport. Most current models have complex forms and generally need to be calibrated by the measured unsaturated hydraulic conductivity curve. A simple model, by which it is possible to conveniently predict the unsaturated hydraulic conductivity, is proposed in this study. The soil–water characteristic curve and hydraulic conductivity curve are separated into three parts. The soil–water characteristic curve is represented by Fredlund and Xing’s equation. A simple model composed of three lines is proposed for estimating the hydraulic conductivity of unsaturated soil. The model parameters can be conveniently calibrated from the measured soil–water characteristic curve and saturated hydraulic conductivity. Finally, the proposed model is validated by the experimental data from different soils. The proposed model provides a simple approach to estimating the hydraulic conductivity of unsaturated soil, which is more convenient for practical application.

Macrophages/microglia are immune system defense and homeostatic cells that develop from bone marrow progenitor cells. According to the different phenotypes and immune responses of macrophages (Th1 and Th2), the two primary categories of polarized macrophages/microglia are those conventionally activated (M1) and alternatively activated (M2). Macrophage/microglial polarization is a key regulating factor in the development of inflammatory disorders, cancers, metabolic disturbances, and neural degeneration. Macrophage/microglial polarization is involved in inflammation, oxidative stress, pathological angiogenesis, and tissue healing processes in ocular diseases, particularly in diabetic retinopathy (DR). The functional phenotypes of macrophages/microglia affect disease progression and prognosis, and thus regulate the polarization or functional phenotype of microglia at different DR stages, which may offer new concepts for individualized therapy of DR. This review summarizes the involvement of macrophage/microglia polarization in physiological situations and in the pathological process of DR, and discusses the promising role of polarization in personalized treatment of DR.

Hsian-tsao gum (HG) possessed of good biological activity and gel-promoting property could improve the textural properties of surimi gel. Ca2+ was commonly used in surimi products, however, effects of Ca2+ on the gel properties of HG-added surimi were not clear. The effects of Ca2+ on the sensory properties, gel properties (gel strength, texture properties, gel-forming forces and microstructure) and in vitro digestibility of HG-added surimi gel were therefore studied. The results showed that Ca2+ reduced the disulfide bonds, ionic bonds and hydrogen bonds, and increased the hydrophobic and non-disulfide covalent bonds, in which the disulfide bonds and non-disulfide covalent bonds determined the gel properties (gel strength, hardness and springiness) and microstructure, thus affecting the gel solubility and in vitro digestibility. Adding 3 mmol/kg Ca2+ could improve sensory properties (elasticity, hardness and tissue status), water holding capacity, gel strength and texture characteristics (hardness, springiness) of HG-added surimi gel, accompanied with the decrease in gel dissolution rate and in vitro digestibility. With the continuous increase of Ca2+ concentration, the structural porosity, gel dissolution rate and in vitro digestibility of HG-surimi gel were increased, but the gel strength, hardness, elasticity and water holding capacity were decreased. Based on PCA results, in vitro gel digestibility was positively correlated to microstructure porosity and gel solubility, but negatively correlated to gel strength, hardness, springiness, water holding capacity and gel forming force (disulfide bonds, ion bonds, hydrogen bonds). Therefore, the HG-added surimi gel with different sensory and structural properties could be designed by adding different concentrations of Ca2+, which provided a theoretical reference for the diversified development of HG-surimi gel products.

ObjectiveThis study aimed to detect circulating tumor cells (CTCs) and circulating tumor-derived endothelial cells (CTECs) in patients with advanced lung cancer, for describing the distribution characteristics of CTC and CTEC subtypes, exploring the correlation between CTC/CTEC subtypes and novel prognostic biomarkers.MethodsA total of 52 patients with advanced lung cancer were enrolled in this study. Using the subtraction enrichment-immunofluorescence in situ hybridization (SE-iFISH) system, CTCs and CTECs derived from these patients were identified.ResultsBased on cell size, there were 49.3% small and 50.7% large CTCs, and 23.0% small and 77.0% large CTECs. Triploidy, tetraploidy, and multiploidy varied in the small and large CTCs/CTECs. Besides these three aneuploid subtypes, monoploidy was found in the small and large CTECs. Triploid and multiploid small CTCs and tetraploid large CTCs were associated with shorter overall survival (OS) in patients with advanced lung cancer. However, none of the CTECs subtypes showed a significant correlation with patient prognosis. In addition, we found strong positive correlations (P

The rapid development of computer science over the past few decades has led to unprecedented progress in the field of artificial intelligence (AI). Its wide application in ophthalmology, especially image processing and data analysis, is particularly extensive and its performance excellent. In recent years, AI has been increasingly applied in optometry with remarkable results. This review is a summary of the application progress of different AI models and algorithms used in optometry (for problems such as myopia, strabismus, amblyopia, keratoconus, and intraocular lens) and includes a discussion of the limitations and challenges associated with its application in this field.

Isocitrate dehydrogenase (IDH) is a key rate-limiting enzyme in the tricarboxylic acid cycle and acts in glutamine synthesis. IDH also participates in plant growth and development and in response to abiotic stresses. We identified 11 maize IDH genes (ZmIDH) and classified these genes into ZmNAD-IDH and ZmNADP-IDH groups based on their different coenzymes (NAD+ or NADP+). The ZmNAD-IDH group was further divided into two subgroups according to their catalytic and non-catalytic subunits, as in Arabidopsis. The ZmIDHs significantly differed in physicochemical properties, gene structure, conserved motifs, and protein tertiary structure. Promoter prediction analysis revealed that the promoters of these ZmIDHs contain cis-acting elements associated with light response, abscisic acid, phytohormones, and abiotic stresses. ZmIDH is predicted to interact with proteins involved in development and stress resistance. Expression analysis of public data revealed that most ZmIDHs are specifically expressed in anthers. Different types of ZmIDHs responded to abiotic stresses with different expression patterns, but all exhibited responses to abiotic stresses to some extent. In addition, analysis of the public sequence from transcription data in an association panel suggested that natural variation in ZmIDH1.4 will be associated with drought tolerance in maize. These results suggested that ZmIDHs respond differently and/or redundantly to abiotic stresses during plant growth and development, and this analysis provides a foundation to understand how ZmIDHs respond to drought stress in maize.

BackgroundPosner-Schlossman syndrome (PSS) is a relatively rare cause of chronic secondary open-angle glaucoma (OAG), but the exact cause is unknown. This study aimed to determine potential risk factors for OAG secondary to PSS and to provide a basis for early intervention in the development of PSS.MethodsThis was a retrospective case-control study. Nine cases diagnosed with PSS and seven cases diagnosed with OAG secondary to PSS were selected and their aqueous humor assays at the first occurrence of PSS were collected. Clinical characteristics including age, sex, disease duration, eye laterality, baseline visual acuity, maximum IOP, corneal endothelial cell density, visual field, retinal nerve fiber layer thickness, cup-to-disk ratio, keratic precipitates, anterior chamber inflammation, and aqueous humor cytokine assay results were compared between the two groups.ResultsThe cytomegalovirus (CMV) positivity was 55.60% in patients with PSS and 100% in patients with OAG secondary to PSS. Corneal endothelial cell density was lower in patients with CMV-positive PSS (p = 0.0116). Concentrations of basic fibroblast growth factor (bFGF), interleukin (IL)-6, and vascular cell adhesion molecule (VCAM) in patients with PSS and IL-8, IL-6, and VCAM in patients with OAG secondary to PSS were higher than standard reference values; and IL-8 concentration was significantly higher in patients with OAG secondary to PSS (p = 0.0229). There were significant positive correlations between IL-8 and IL-6, IL-6 and VCAM (p = 0.0304, p = 0.0172) and a significant negative correlation between bFGF and vascular endothelial growth factor (VEGF) (p = 0.0497). Simultaneous increase of IL-8 and IL-6 concentration levels could be used as a cytokine indicator to predict secondary OAG in patients with PSS (p = 0.0095).ConclusionSimultaneous increase of IL-8 and IL-6 concentrations may be an important cause of accelerated secondary OAG in patients with PSS, with IL-8 playing a more critical role. IL-8 and IL-6 may be more reliable cytokine markers for predicting secondary OAG in PSS, However, the high possibility of secondary OAG in patients with CMV-positive PSS should not be ignored. Regulation of IL-8 and IL-6 levels may be a new strategy of preventing OAG secondary to PSS.

Abstract Background Small cell lung cancer (SCLC) is characterized by aggressive spread and poor prognosis, but has limited treatment options. Results of prognostic factors from randomized trials on treatment arrangement are conflicting and large‐scale real‐world analysis is lacking. Methods Patients diagnosed SCLC between 2008 and 2018 in Peking University Cancer Hospital were included in this study. Kaplan–Meier methods were adopted, and univariate analysis and multivariate Cox regression models were constructed to analyze prognostic factors. Results Among 1045 patients who presented to our center, 988 eligible patients were identified. Median overall survival (OS) was 16.0 months for the whole group, 24.0 months and 11.0 months for limited stage small cell lung cancer (LS‐SCLC) and extensive stage small cell lung cancer (ES‐SCLC), separately. Limited‐stage, good performance status (PS) (ECOG 0–1), response to primary systemic treatment, and patients who received initiative irradiation and three or more lines of chemotherapy were predicted to have better OS in the whole group. Only response to first‐line systemic therapy and prophylactic cranial irradiation (PCI) were independent prognostic factors of survival in LS‐SCLC; while good PS (ECOG 0–1), without liver, bone, or subcutaneous metastases, response to first‐line therapy, initial local irradiation, and three or more lines of systemic therapy predicted a favorable prognosis in ES‐SCLC. Conclusions The present study retrieved from large real–world data suggested that response to primary systemic therapy and aggressive radiotherapy are independent prognostic factors for SCLC. PCI and initiative irradiation for original or metastatic sites improved the OS in LS‐SCLC and ES‐SCLC, respectively.

Abstract Growth of high-quality III–V nanowires at a low cost for optoelectronic and electronic applications is a long-term pursuit of research. Still, controlled synthesis of III–V nanowires using chemical vapor deposition method is challenge and lack theory guidance. Here, we show the growth of InP and GaP nanowires in a large area with a high density using a vacuum chemical vapor deposition method. It is revealed that high growth temperature is required to avoid oxide formation and increase the crystal purity of InP nanowires. Introduction of a small amount of Ga into the reactor leads to the formation of GaP nanowires instead of ternary InGaP nanowires. Thermodynamic calculation within the calculation of phase diagrams (CALPHAD) approach is applied to explain this novel growth phenomenon. Composition and driving force calculations of the solidification process demonstrate that only 1 at.% of Ga in the catalyst is enough to tune the nanowire formation from InP to GaP, since GaP nucleation shows a much larger driving force. The combined thermodynamic studies together with III–V nanowire growth studies provide an excellent example to guide the nanowire growth.

Abstract Background Aspartate β-hydroxylase (ASPH) is silent in normal adult tissues only to re-emerge during oncogenesis where its function is required for generation and maintenance of malignant phenotypes. Exosomes enable prooncogenic secretome delivering and trafficking for long-distance cell-to-cell communication. This study aims to explore molecular mechanisms underlying how ASPH network regulates designated exosomes to program development and progression of breast cancer. Methods Stable cell lines overexpressing or knocking-out of ASPH were established using lentivirus transfection or CRISPR-CAS9 systems. Western blot, MTT, immunofluorescence, luciferase reporter, co-immunoprecipitation, 2D/3-D invasion, tube formation, mammosphere formation, immunohistochemistry and newly developed in vitro metastasis were applied. Results Through physical interactions with Notch receptors, ligands (JAGs) and regulators (ADAM10/17), ASPH activates Notch cascade to provide raw materials (especially MMPs/ADAMs) for synthesis/release of pro-metastatic exosomes. Exosomes orchestrate EMT, 2-D/3-D invasion, stemness, angiogenesis, and premetastatic niche formation. Small molecule inhibitors (SMIs) of ASPH’s β-hydroxylase specifically/efficiently abrogated in vitro metastasis, which mimics basement membrane invasion at primary site, intravasation/extravasation (transendothelial migration), and colonization/outgrowth at distant sites. Multiple organ-metastases in orthotopic and tail vein injection murine models were substantially blocked by a specific SMI. ASPH is silenced in normal adult breast, upregulated from in situ malignancies to highly expressed in invasive/advanced ductal carcinoma. Moderate-high expression of ASPH confers more aggressive molecular subtypes (TNBC or Her2 amplified), early recurrence/progression and devastating outcome (reduced overall/disease-free survival) of breast cancer. Expression profiling of Notch signaling components positively correlates with ASPH expression in breast cancer patients, confirming that ASPH-Notch axis acts functionally in breast tumorigenesis. Conclusions ASPH-Notch axis guides particularly selective exosomes to potentiate multifaceted metastasis. ASPH’s pro-oncogenic/pro-metastatic properties are essential for breast cancer development/progression, revealing a potential target for therapy.

Objective: Pembrolizumab and bevacizumab both have antitumor activity. According to NCCN updated guideline the benefit of pembrolizumab or bevacizumab as a first line in management of advanced nonsmall cell lung cancer (NSCLC) is documented in randomized controlled studies. The study aimed to evaluate the response and complications of patients with advanced NSCLC treated with pembrolizumab or bevacizumab plus chemotherapy. Methods: This study was a retrospective cohort study of patients with advanced nonsquamous NSCLC who received cisplatin with pemetrexed combined with pembrolizumab (A group) or bevacizumab (B group) from 07/02/2018 to 07/03/2021 at Peking University Cancer Hospital. Progression-free survival (PFS) was the primary outcome. The secondary outcomes included overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR), and adverse events (AEs). Results: This study included 66 patients, 34 in A group and 32 in B group. There were no differences in median PFS (7.6 vs 9.9 months, P = .601). There were no differences in median OS (23.1 vs 24.2 months, P = .782). There were no differences in ORR (57.6 % vs 41.9 % , P = .211) and DCR (93.9 % vs 100.0 % , P = .164) between 2 groups. The occurrence of AEs was similar. No new safety signals were observed. Grade 3 to 4 treatment-related AEs occurred in 17 (50.0 % ) patients of A group and in 12 (37.5 % ) of B group ( P > .05). Conclusion: The addition of pembrolizumab or bevacizumab to pemetrexed plus cisplatin was well tolerated and resulted in a clinically meaningful treatment benefit in advanced nonsquamous NSCLC. When pembrolizumab is not suitable, bevacizumab plus chemotherapy may be an option.

Apple Alternaria blotch disease, caused by Alternaria alternata (Fr.) Keissl, is one of the most famous leaf diseases. When the disease is prevalent, it causes leaf abscission and influences the formation of flower buds and photosynthesis. Therefore, a simple, rapid, high-specificity and sensitivity method for monitoring infected leaves at early developmental stages is urgently needed, so that the occurrence and expansion of A. alternata can be controlled in time. In our research, a rapid, specific and efficient loop-mediated isothermal amplification (LAMP) method was developed to detect A. alternata within 60 min. Six primers of LAMP detection can only specifically amplify the aapg-1 gene in A. alternata but not in four other important fungi in apples. The aapg-1 gene encodes endopolygalacturonase in A. alternata, and there are significant differences among different species. Thus, it was applied as the target for LAMP primers. Compared to conventional PCR detection, our LAMP method had the same sensitivity as that of detecting as little as 1 fg of pure genomic DNA of A. alternata. When leaves were inoculated with A. alternata conidia, LAMP detected 1 × 102 conidia/mL as the minimum concentration. However, the traditional tissue isolation and identification method only isolated A. alternata from leaves inoculated with 1 × 105 and 1 × 106 conidia/mL, indicating that the LAMP method was more sensitive than the traditional tissue isolation and identification method for A. alternata before symptoms. Further tests also indicated that LAMP detection was more accurate and sensitive than the traditional tissue isolation and identification method for A. alternata in leaves with the Alternaria blotch symptom collected from the field. Our results showed that the LAMP-targeting the aapg-1 gene has the advantages of high sensitivity, specificity and simplicity and can be used for rapid detection and early monitoring of A. alternata in the field. LAMP is instructive for us to effectively prevent and control apple Alternaria blotch disease.

The comparative efficacy of trifocal and bifocal intraocular lenses (IOLs) remained uncertain among patients undergoing cataract surgery. A systematic review and meta-analysis was performed to answer this question. PubMed, Cochrane Library and Embase were searched to capture relevant randomized controlled trials (RCTs). Visual acuity (VA) and patient's satisfaction were regarded as primary outcomes. Secondary outcomes included residual sphere, spherical equivalence, residual cylinder, posterior capsular opacification (PCO), spectacle independence, and other complications. Statistical analysis was done using RevMan 5.2.0. A total of 9 studies (11 RCTs) with 297 participants (558 eyes) were included. Meta-analysis showed significant differences between trifocal and bifocal IOLs in the uncorrected near VA (mean difference [MD], −0.008; 95% confidence interval [Cl], −0.015 to −0.001; P = 0.028) and uncorrected intermediate VA (MD, −0.06; 95% CI, −0.10 to −0.02; P < 0.01). Trifocal IOLs were associated with decreased PCO incidence when compared to bifocal IOLs (relative risk [RR], 0.54; 95% CI, 0.31 to 0.95; P = 0.03). Trifocal IOLs may be superior to bifocal IOLs because of its improved intermediate VA and reduced incidence of PCO.

Competitive agri-food supply chain (hereafter, AFSC) is an important component of AFSC. In a competitive environment, more and more AFSCs use blockchain-based traceability services (hereafter, BBTS) to improve the traceability level of agricultural products. The investment rules concerning BBTS and the coordination rules in an AFSC are vital issues for many firms who want to adopt BBTS. To explore these laws, we constructed two competitive AFSCs, each of which included a supplier and a retailer. Considering the new changes in consumers’ perception of product quality and safety after using the BBTS, the demand function was modified. Then we built the income functions of chain members under three situations of investment. The research found that: (1) the improvement of customers’ perceived quality by using the BBTS can increase their benefits; (2) when decision-makers want to invest in the BBTS, they should pay attention to consumers’ perceived quality safety factor for their competitive products; (3) when the investment cost is greater than its threshold value, two competitive AFSCs should invest in the BBTS together.

Background This real‐world study assessed the efficacy and toxicity of anlotinib as salvage treatment in Chinese patients with advanced non‐small cell lung cancer (NSCLC). Methods The medical records of 81 patients with advanced NSCLC who had failed at least two lines of chemotherapy were retrospectively collected. All patients were administered anlotinib treatment until disease progression or intolerance as a result of adverse events. Survival curves were created using the Kaplan–Meier method. The log‐rank test was used for univariate analysis of progression‐free survival (PFS) between groups. Cox regression was used to estimate the statistically significant factors based on univariate analysis. Results The median PFS was five months (95% confidence interval [CI] 3.5–6.5). The objective response rate (ORR) was 7% and the disease control rate (DCR) was 84%. The following subgroups of patients had longer PFS (P

Background Thymoma and thymic carcinoma are rare thymic epithelial tumors. We investigated the efficacy of first‐line gemcitabine and cisplatin (GP) chemotherapy versus gemcitabine and cisplatin chemotherapy combined with the anti‐angiogenic drug endostar (GP + E) in advanced thymoma and thymic carcinoma. Methods The records of 45 patients with invasive metastatic thymomas or thymic carcinomas treated with GP as first‐line therapy between August 2008 and July 2017 at the Department of Respiratory Medicine, Peking University Cancer Hospital and Institute were retrospectively reviewed. Results Eighteen patients (75%) in the GP + E group achieved a partial response and six (25%) had stable disease. In GP only group, nine (42.8%) patients achieved a partial response, 11 (52.4%) had stable disease, and one (4.8%) had progressive disease. The GP + E group had a significantly higher overall response rate (75% vs. 42.9%; P = 0.028), and median progression‐free survival (PFS) and overall survival (OS) of 19 and 76 months, respectively. In the GP only group, median PFS and OS were 16 and 29 months, respectively. PFS and OS were not significantly different between the groups. Conclusions GP has moderate efficacy and could represent a suitable first‐line therapy for thymic carcinoma and thymoma. Chemotherapy combined with endostar could improve the overall response rate, but did not prolong PFS or OS.

BackgroundProgrammed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors are increasingly used in China, but no real-world data are available about the immune-related adverse events (irAEs). This real-world retrospective study aimed to assess the safety and effectiveness of PD-1/PD-L1 inhibitors in patients with non-small cell lung cancer (NSCLC) and to analyze the association between irAEs and effectiveness.MethodsThis was a retrospective study of the clinical data of patients with NSCLC treated with PD-1/PD-L1 inhibitors from August 2016 to November 2019 at Beijing Cancer Hospital. The patients were divided into the irAE or non-irAE groups. Overall adverse events, the impact of irAE on tumor response, and the association of irAEs with effectiveness were evaluated.ResultsOne hundred and ninety-one patients were included, including 70 (36.6%) patients in the irAE group and 121 (63.4%) patients in the non-irAE group. AE, grades 3–5 AEs, and irAE occurred in 107 (56.0%), 24 (12.6%), and 70 (36.6%) of the patients, respectively. The objective response rate (ORR) and disease control rate (DCR) were higher in the irAE group compared with the non-irAE group (42.0% vs. 25.8%, P=0.038; 91.9% vs. 70.8%, P=0.002). Multivariable analyses identified that irAE were associated with progression-free survival (HR=0.62, 95%CI: 0.43–0.91; P=0.015), but not with overall survival (HR=0.76, 95%CI: 0.44–1.28; P=0.299).ConclusionIn NSCLC treated with PD-1/PD-L1 inhibitors, patients with irAEs showed improved effectiveness over patients without irAEs. Future studies of anti-PD-1/PD-L1 immunotherapy should explore this association and the underlying biological mechanisms of efficacy.

We experimentally demonstrate an optical-wireless transmission system at W band, which can support long-distance wireless transmission and tolerate some frequency difference of the local oscillators (LOs) at the receiver. The generation of millimeter-wave signal is based on the photonic technique by heterodyne mixing of an optical polarization division multiplexing quadrature phase shift keying (PDM-QPSK) signal and an optical LO signal. After 20-km fiber transmission, tens of gigabit-per-second millimeter-wave signals are delivered over multiple-input-multiple-output (MIMO) wireless links by different polarization antennas. Then, analog downconversion is performed before the received signal is demodulated by coherent detection and advanced digital signal processing. Using this system, we experimentally demonstrate the transmission of 18.7-, 29.9-, and 37.4-Gb/s PDM-QPSK wireless signals at W band over 80-, 40-, and 20-m wireless links, respectively, with bit error rate less than the forward error correction threshold of 3.8 × 10-3. In addition, we investigate the effect of different frequency LOs on the MIMO system performance, finding that the system can tolerate about 1.25-GHz frequency difference for a 10-Gbaud signal. The proposed system can be suitable for the building-to-building broadband connection, in-building hybrid fiber-wireless access networks, and some scenarios that bridge natural obstacles and difficult-to-access terrain.

In this paper, we propose a novel and simple method to generate millimeter-wave vector signals using only one phase modulator (PM) and phase-precoding technique, in which the precoded microwave vector signal is used for the drive of the single PM. We experimentally demonstrate that this concept of the generation of quadrature-phase-shift-keying-modulated vector signal can be employed in our radio-over-fiber (RoF) system architecture based on our proposed scheme. By this scheme, we simplify the configuration and reduce the cost of the RoF system.

dot-app is a Cytoscape 3 app that allows Cytoscape to import and export Graphviz (.dot, .gv) files, also known as DOT files due to the .dot extension and their conformance to the DOT language syntax. The DOT format was originally created in the early 2000s to represent graph topologies, layouts and formatting. DOT-encoded files are produced and consumed by a number of open-source graph applications, including Graphviz, Gephi, Tulip, and others. While DOT-based graph applications are popular, they emphasize general graph layout and styling over the topological and semantic analysis functions available in domain-focused applications such as Cytoscape. While domain-focused applications have easy access to large networks (10,000 to 100,000 nodes) and advanced analysis and formatting, they do not have as many styling options as the Graphviz software suite. dot-app enables the interchange of networks between Cytoscape and DOT-compatible applications so that users can benefit from the features of both. dot-app was first deployed to the Cytoscape App Store in August 2015, has since registered more than 1,200 downloads, and has been highly rated by more than 20 users.

dot-app is a Cytoscape 3 app that allows Cytoscape to import and export Graphviz (*.dot, *.gv) files, also known as DOT files due to the *.dot extension and their conformance to the DOT language syntax. The DOT format was originally created in the early 2000s to represent graph topologies, layouts and formatting. DOT-encoded files are produced and consumed by a number of open-source graph applications, including GraphViz, Gephi, neato, smyrna, and others. While DOT-based graph applications are popular, they emphasize general graph layout and styling over the topological and semantic analysis functions available in domain-focused applications such as Cytoscape. While domain-focused applications have easy access to large networks (10,000 to 100,000 nodes) and advanced analysis and formatting, they do not offer all of the styling options that DOT-based applications (particularly GraphViz) do. dot-app enables the interchange of networks between Cytoscape and DOT-based applications so that users can benefit from the features of both. dot-app was first deployed to the Cytoscape App Store in August 2015, has since registered more than 1,200 downloads, and has been highly rated by more than 20 users.