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The development and change patterns as well as the disease course management of multiple ground-glass nodules (GGNs) in the lungs are currently hotspots and difficulties in clinical lung cancer research. Understanding the latest advancements in the natural history of multiple GGNs is crucial for grasping the disease variation patterns and formulating management strategies. Meanwhile, utilizing advanced methods such as intelligent follow-up management platforms makes the long-term standardized management of GGNs possible. Therefore, this article provides an overview of the latest research advancements on the natural history of multiple GGNs and new experience in GGNs management.

Abstract. Liver metastases (LMs) are common in lung cancer. Despite substantial advances in diagnosis and treatment, the survival rate of patients with LM remains low as the immune-suppressive microenvironment of the liver allows tumor cells to evade the immune system. The impact of LMs on the outcomes of immune checkpoint inhibitors in patients with solid tumors has been the main focus of recent translational and clinical research. Growing evidence indicates that the hepatic microenvironment delivers paracrine and autocrine signals from non-parenchymal and parenchymal cells. Overall, these microenvironments create pre- and post-metastatic conditions for the progression of LMs. Herein, we reviewed the epidemiology, physiology, pathology and immunology, of LMs associated with non-small cell lung cancer and the role and potential targets of the liver microenvironment in LM in each phase of metastasis. Additionally, we reviewed the current treatment strategies and challenges that should be overcome in preclinical and clinical investigations. These approaches target liver elements as the basis for future clinical trials, including combinatorial interventions reported to resolve hepatic immune suppression, such as immunotherapy plus chemotherapy, immunotherapy plus radiotherapy, immunotherapy plus anti-angiogenesis therapy, and surgical resection.

Background At the beginning of December 2022, the Chinese government made major adjustments to the epidemic prevention and control measures. The epidemic infection data and laboratory makers for infected patients based on this period may help with the management and prognostication of COVID-19 patients.Methods The COVID-19 patients hospitalized during December 2022 were enrolled. Logistic regression analysis was used to screen significant factors associated with mortality in patients with COVID-19. Candidate variables were screened by LASSO and stepwise logistic regression methods and were used to construct logistic regression as the prognostic model. The performance of the models was evaluated by discrimination, calibration, and net benefit.Results 888 patients were eligible, consisting of 715 survivors and 173 all-cause deaths. Factors significantly associated with mortality in COVID-19 patients were: lactate dehydrogenase (LDH), albumin (ALB), procalcitonin (PCT), age, smoking history, malignancy history, high density lipoprotein cholesterol (HDL-C), lactate, vaccine status and urea. 335 of the 888 eligible patients were defined as ICU cases. Seven predictors, including neutrophil to lymphocyte ratio, D-dimer, PCT, C-reactive protein, ALB, bicarbonate, and LDH, were finally selected to establish the prognostic model and generate a nomogram. The area under the curve of the receiver operating curve in the training and validation cohorts were respectively 0.842 and 0.853. In terms of calibration, predicted probabilities and observed proportions displayed high agreements. Decision curve analysis showed high clinical net benefit in the risk threshold of 0.10-0.85. A cutoff value of 81.220 was determined to predict the outcome of COVID-19 patients via this nomogram.Conclusions The laboratory model established in this study showed high discrimination, calibration, and net benefit. It may be used for early identification of severe patients with COVID-19.

Graveoline exhibits various biological activities. However, only limited studies have focused on its hepatoprotective properties. This study evaluated the anti-inflammatory and hepatoprotective activities of graveoline, a minor 2-phenylquinolin-4-one alkaloid isolated from Ruta graveolens L., in a liver injury model in vitro and in vivo. A network pharmacology approach was used to investigate the potential signaling pathway associated with the hepatoprotective activity of graveoline. Subsequently, biological experiments were conducted to validate the findings. Topological analysis of the KEGG pathway enrichment revealed that graveoline mediates its hepatoprotective activity through genes associated with the hepatitis B viral infection pathway. Biological experiments demonstrated that graveoline effectively reduced the levels of alanine transaminase and aspartate transaminase in lipopolysaccharide (LPS)-induced HepG2 cells. Graveoline exerted antihepatitic activity by inhibiting the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) and elevated the anti-inflammatory cytokines interleukin-4 (IL-4) and interleukin-10 (IL-10) in vitro and in vivo. Additionally, graveoline exerted its hepatoprotective activity by inhibiting JAK1 and STAT3 phosphorylation both in vitro and in vivo. In summary, graveoline can attenuate acute liver injury by inhibiting the TNF-α inflammasome, activating IL-4 and IL-10, and suppressing the JAK1/STAT3 signaling pathway. This study sheds light on the potential of graveoline as a promising therapeutic agent for treating liver injury.

Microbubble-mediated therapeutic gene or drug delivery is a promising strategy for various cardiovascular diseases (CVDs), but the efficiency and precision need to be improved. Here, we propose a cavitation bubble-driven drug delivery strategy that can be applied to CVDs. A bubble-pulse-driving theory was proposed, and the formula of time-averaged thrust driven by bubble pulses was derived. The continuous motion of particles propelled by cavitation bubbles in the ultrasonic field is investigated experimentally by high-speed photography. The cavitation bubbles grow and collapse continuously, and generate periodic pulse thrust to drive the particles to move in the liquid. Particles attached to bubbles will move in various ways, such as ejection, collision, translation, rotation, attitude variation, and circular motion. The cavity attached to the particle is a relatively large cavitation bubble, which does not collapse to the particle surface, but to the axis of the bubble perpendicular to the particle surface. The cavitation bubble expands spherically and collapses asymmetrically, which makes the push on the particle generated by the bubble expansion greater than the pull on the particle generated by the bubble collapse. The time-averaged force of the cavitation bubble during its growth and collapse is the cavitation-bubble-driven force that propels the particle. Both the cavitation-bubble-driven force and the primary Bjerknes force act in the same position on the particle surface, but in different directions. In addition to the above two forces, particles are also affected by the mass force acting on the center of mass and the motion resistance acting on the surface, so the complex motion of particles can be explained.

Targeted therapy and immunotherapy are both important in the treatment of non-small-cell lung cancer (NSCLC). Accurate diagnose and precise treatment are key in achieving long survival of patients. MET fusion is a rare oncogenic factor, whose optimal detection and treatment are not well established. Here, we report on a 32-year-old female lung adenocarcinoma patient with positive PD-L1 and negative driver gene detected by DNA-based next-generation sequencing (NGS). A radical resection of the primary lesion after chemotherapy combined with PD-1 checkpoint inhibitor administration indicated primary immuno-resistance according to her pathological response and rapid relapse. A rare CD47-MET was detected by RNA-based NGS, which was confirmed by fluorescence in situ hybridization. Multiplex immunofluorescence revealed a PD-L1 related heterogeneous immunosuppressive microenvironment with little distribution of CD4+ T cells and CD8+ T cells. Savolitinib therapy resulted in a progression-free survival (PFS) of >12 months, until a new secondary resistance mutation in MET p.D1228H was detected by re-biopsy and joint DNA-RNA-based NGS after disease progression. In this case, CD47-MET fusion NSCLC was primarily resistant to immunotherapy, sensitive to savolitinib, and developed secondary MET p.D1228H mutation after targeted treatment. DNA-RNA-based NGS is useful in the detection of such molecular events and tracking of secondary mutations in drug resistance. To this end, DNA-RNA-based NGS may be of better value in guiding precise diagnosis and individualized treatment in this patient population.

To compare the pretreatment effect of deep eutectic solvents (DESs) on corn stover, three types of DESs (acid, neutral, and alkaline) were used to pretreat corn stover, and their effects on lignin removal were investigated. Then the performance of photo-fermentation hydrogen production (PFHP) using DESs pretreated corn stover was compared and analyzed. The results showed that acid DESs had the best lignin removal efficiency, and the lignin removal percentages of choline chloride/formic acid (ChCl/Fac) and choline chloride/oxalate (ChCl/Oac) were 64.7% and 65.6%, respectively. The alkaline DESs had the second highest removal of lignin, while the neutral DESs had a poor effect on lignin removal. The comparison of hydrogen production indicated that the corn stover pretreated with ChCl/Oac had the best hydrogen production effect. In conclusion, the DESs pretreatment can obviously remove the lignin in corn stover, and then improve the hydrogen production capacity and efficiency of photo-fermentation, which provides a potential pretreatment method for the efficient utilization of straw biomass.

Abstract Poly (ADP-ribose) polymerase inhibitors (PARPi) are selectively active in ovarian cancer (OC) with homologous recombination (HR) deficiency (HRD) caused by mutations in BRCA1/2 and other DNA repair pathway members. We sought molecular targeted therapy that induce HRD in HR-proficient cells to induce synthetic lethality with PARPi and extend the utility of PARPi. Here, we demonstrate that lysine-specific demethylase 1 (LSD1) is an important regulator for OC. Importantly, genetic depletion or pharmacological inhibition of LSD1 induces HRD and sensitizes HR-proficient OC cells to PARPi in vitro and in multiple in vivo models. Mechanistically, LSD1 inhibition directly impairs transcription of BRCA1/2 and RAD51, three genes essential for HR, dependently of its canonical demethylase function. Collectively, our work indicates combination with LSD1 inhibitor could greatly expand the utility of PARPi to patients with HR-proficient tumor, warranting assessment in human clinical trials.

Abstract Background Recently, chemotherapy plus immunotherapy has achieved remarkable efficacy in lung squamous cell carcinoma (LUSC). However, some patients, especially frail people, cannot tolerate full‐dose chemotherapy in the real world. To reduce toxicity, appropriate dose reduction in chemotherapy is necessary. Therefore, this study aimed to demonstrate the efficacy and safety of reduced‐dose chemotherapy plus immunotherapy in LUSC patients in the real world. Methods A real‐world observational study was conducted concerning patients who received chemotherapy plus immunotherapy in our situation. The primary endpoints were objective response rate (ORR) and disease control rate (DCR), and the secondary endpoints were progression‐free survival (PFS), overall survival (OS), and toxicity. Results Between December 2018 and January 2022, 110 patients were enrolled, of whom 54 patients were chemotherapy reduced‐dose group and 56 patients were chemotherapy standard‐dose group. The ORR in the reduced‐dose group is similar to standard‐dose group (85.19% vs. 71.43%, p = 0.082). Similar DCR were observed (100% vs. 94.64%, p = 0.086). Median PFS was 12 months in the reduced‐dose group and standard‐dose group, respectively. Median OS was 15 months and 16 months in the reduced‐dose group and standard‐dose group, respectively. We reported a lower incidence of grade 3–4 toxicity in the reduced‐dose group compared with standard‐dose group (27.78% vs. 42.86%, p = 0.100). The major toxic reactions were better alleviated in the reduced‐dose group than in the standard‐dose group, especially in the thrombocytopenia (p = 0.044), peripheral nerve damage (p = 0.001), gastrointestinal reactions (p

Abstract Aims To examine how metabolic status is associated with microvascular phenotype and to identify variables associated with vascular remodeling after bariatric surgery, using noninvasive optical coherence tomography angiography (OCTA). Methods The study included 136 obese subjects scheduled for bariatric surgery and 52 normal‐weight controls. Patients with obesity were divided into metabolically healthy obesity (MHO) and metabolic syndrome (MetS) groups according to the diagnosis criteria of the Chinese Diabetes Society. Retinal microvascular parameters were measured by OCTA, including superficial capillary plexus (SCP) and deep capillary plexus (DCP) vessel densities. Follow‐ups were performed at the baseline and 6 months after bariatric surgery. Results Fovea SCP, average DCP, fovea DCP, parafovea DCP, and perifovea DCP vessel densities were significantly lower in the MetS group, compared to controls (19.91% vs. 22.49%, 51.60% vs. 54.20%, 36.64% vs. 39.14%, 56.24% vs. 57.65% and 52.59% vs. 55.58%, respectively, all p

Ultrasound-induced cavitation in blood vessels is a common scenario in medical procedures. This paper focuses on understanding the mechanism of microscopic damage to vessel walls caused by the evolution of cavitation bubbles within the vessels. In this study, cavitation bubbles were generated using the low-voltage discharge method in 0.9% sodium chloride saline, and vessel models with wall thicknesses ranging from 0.7 mm to 2 mm were made using a 3D laminating process. The interaction between cavitation bubbles and vessel models with different wall thicknesses was observed using a combination of high-speed photography. Results show that cavitation bubble morphology and collapse time increased and then stabilized as the vessel wall thickness increased. When the cavitation bubble was located in vessel axial line, pair of opposing micro-jets were formed along the axis of the vessel, and the peak of micro-jet velocity decreased with increasing wall thickness. However, when the cavitation bubble deviated from the vessel model center, no micro-jet towards the vessel model wall was observed. Further analysis of the vessel wall deformation under varying distances from the cavitation bubble to the vessel wall revealed that the magnitude of vessel wall stretch due to the cavitation bubble expansion was greater than that of the contraction. A comparative analysis of the interaction of between the cavitation bubble and different forms of elastic membranes showed that the oscillation period of the cavitation bubble under the influence of elastic vessel model was lower than the elastic membrane. Furthermore, the degree of deformation of elastic vessel models under the expansion of the cavitation bubble was smaller than that of elastic membranes, whereas the degree of deformation of elastic vessel models in the contraction phase of the cavitation bubble was larger than that of elastic membranes. These new findings provide important theoretical insights into the microscopic mechanisms of blood vessel potential damage caused by ultrasound-induced cavitation bubble, as well as cavitation in pipelines in hydrodynamic systems.

Context The extracts of Aspongopus chinensis Dallas (Pentatomidae), an insect used in traditional Chinese medicine, have a complex chemical composition and possess multiple pharmacological activities.Objective This study comprehensively characterizes the chemical constituents of A. chinensis by an integrated targeted and untargeted strategy using UPLC-QTOF-MS combined with molecular networking.Materials and methods The ultra-performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) combined with molecular networking-based dereplication was proposed to facilitate the identification of the chemical constituents of aqueous and ethanol extracts of A. chinensis. The overall strategy was designed to avoid the inefficiency and costliness of traditional techniques. The targeted compounds discovered in the A. chinensis extracts were identified by searching a self-built database, including fragment ions, precursor ion mass, and other structural information. The untargeted compounds were identified by analyzing the relationship between different categories, fragmentation pathways, mass spectrometry data, and the structure of the same cluster of nodes within the molecular network. The untargeted strategy was verified using commercial standard samples under the same mass spectrometry conditions.Results The proposed integrated targeted and untargeted strategy was successfully applied to the comprehensive profiling of the chemical constituents of aqueous and ethanol extracts of A. chinensis. A total of 124 compounds such as fatty acids, nucleosides, amino acids, and peptides, including 74 compounds that were reported for the first time, were identified in this study.Conclusions The integrated strategy using LC tandem HRMS combined with molecular networking could be popularised for the comprehensive profiling of chemical constituents of other traditional insect medicines.

IntroductionSesame seeds have become an irreplaceable source of edible oils and food products with rich nutrients and a unique flavor, and their metabolite contents and physiological functions vary widely across different seed coat colors. Although the quantitative trait loci (QTLs) for genetic variation in seed coat color have been extensively investigated, the identification of unique genetic loci for intermediate colors such as brown has not been reported due to their complexity.MethodsHere, we crossed the white sesame ‘Yuzhi No. 8’ (YZ8) and the brown sesame ‘Yanzhou Erhongpi’ (YZEHP) to construct a recombinant inbred line (RIL) population with consecutive self-fertilization for ten generations.ResultsThe selfed F1 seeds were brown which was controlled by a dominant gene. Based on the genotyping by whole-genome resequencing of the RILs, a major-effect QTL for brown coat color was identified through both bulk segregant analysis (BSA) and genetic linkage mapping in sesame, which was located within a 1.19 Mb interval on chromosome 6 (qBSCchr6). Moreover, we found that the YZEHP seed coat initially became pigmented at 20 days post-anthesis (DPA) and was substantially colored at 30 DPA. We screened 13 possible candidate genes based on the effects of genetic variants on protein coding and predicted gene functions. Furthermore, qRT‒PCR was used to verify the expression patterns of these genes in different post-anthesis developmental periods. We noted that in comparison to YZ8 seeds, YZEHP seeds had expression of SIN_1023239 that was significantly up-regulated 2.5-, 9.41-, 6.0-, and 5.9-fold at 15, 20, 25, and 30 DPA, respectively, which was consistent with the pattern of brown seed coat pigment accumulation.DiscussionThis study identified the first major-effect QTL for the control of the brown seed coat trait in sesame. This finding lays the foundation for further fine mapping and cloning as well as investigating the regulatory mechanism of seed coat color in sesame.

Interleukin (IL)‐36α, a newly recognized IL‐1 family member, has been previously reported to play a pivotal role in autoimmunity diseases and acute inflammatory reactions. Recently, several studies have indicated that IL‐36α has potential anticancer effects against certain types of cancer. However, the expression pattern and functional role of IL‐36α in non‐small cell lung cancer (NSCLC) have not been elucidated. Here, we report that the mRNA and protein levels of IL‐36α are significantly reduced in NSCLC tissues. Low levels of intratumoral IL‐36α are correlated with higher tumor status, advanced TNM stage, increased vascular invasion and shorter overall survival (OS). Intratumoral IL‐36α expression is an independent prognostic factor for OS (hazard ratio = 3.081; P = 0.012) in patients with NSCLC. Overexpression of IL‐36α in lung cancer cells did not disturb cell proliferation, apoptosis or cell‐cycle distribution in vitro, but markedly inhibited tumor growth in vivo. Mechanistically, IL‐36α reduced the expression and secretion of vascular endothelial growth factor A through inhibiting hypoxia‐inducible factor 1α expression. Finally, decreased IL‐36α expression was associated with high microvessel density and vascular endothelial growth factor A in patients with NSCLC. Together, our findings suggest that IL‐36α expression is a valuable marker indicating poor prognosis in patients with NSCLC.

In this article, an effective clutter suppression and moving target imaging approach is proposed for the geosynchronous-low earth orbit (GEO-LEO) bistatic multichannel synthetic aperture radar (SAR) system, which is robust for the fast moving target with Doppler centroid ambiguity. For the GEO-LEO bistatic multichannel SAR system, the characteristic of baseline with azimuth invariant in Doppler Fourier transform domain is not tenable. It is difficult to implement clutter suppression by the unified baseline compensation in azimuth Doppler Fourier transform domain. Fortunately, we discover that the baseline can be approximately regarded as a constant in chirp Fourier transform domain for the GEO-LEO bistatic multichannel SAR system. Hence, the corresponding baseline compensation can be achieved in the azimuth chirp Fourier transform domain for the clutter. With an orthogonality vector of clutter, the clutter can be well suppressed and the moving target is extracted. After that, the moving target imaging approach is developed with the baseband Doppler centroid estimation and Doppler ambiguity number estimation. Finally, the theoretical investigations and the proposed approach in this article are validated by some experiments, where the experiments for clutter suppression and experiments for fast moving targets are included. Especially, an experiment with real SAR scattering scene is involved. In addition, some discussions for blind velocity targets are presented.

The histological transformation from lung squamous cell carcinoma (LUSC) to lung adenocarcinoma (LUAD) and p. N771delinsGF mutations in EGFR exon 20 (ex20) are exceedingly rare in non–small cell lung carcinoma (NSCLC). EGFR ex20 mutations are insensitive to EGFR tyrosine kinase inhibitors in NSCLC. Here, we present a 76-year-old male smoker harboring LUAD with a novel p. N771delinsGF deletion/insertion mutation in EGFR ex20 transdifferentiating from advanced LUSC after chemoradiotherapy. The patient presented reduced hydrothorax and relieved tightness with the treatment of nivolumab plus docetaxel and carboplatin after the failure of second-line chemotherapy. The case highlights the importance of rebiopsy and molecular retesting after the progression of lung cancer and supports the idea that the combination of immune checkpoint blockade and chemotherapy may be an attractive option for patients with EGFR ex20 mutations associated with LUSC–LUAD transformation.

Over the years, there has been a high demand for developing new safe and effective drug carriers for cancer therapy. Emerging studies have indicated that exosomes can serve as potent therapeutic carriers since they offer low immunogenicity, high stability, innate and acquired targetability, and the stimulation of anti-cancer immune responses. Yet, the development of exosome-based drug delivery systems remains challenging due to their heterogeneity, low yield, and limited drug loading efficiency. Herein, we summarized the current application of exosomes derived from different cells as drug carriers in anti-cancer therapy in vitro and in vivo. We also discussed the challenges and prospects of exosome-based drug delivery systems in cancer therapy.

The inherent unknown deformations of inverse synthetic aperture radar (ISAR) images, such as translation, scaling, and rotation, pose great challenges to space target classification. To achieve high-precision classification for ISAR images, a deformation-robust ISAR image classification network using contrastive learning (CL), i.e., CLISAR-Net, is proposed for deformation ISAR image classification. Unlike traditional supervised learning methods, CLISAR-Net develops a new unsupervised pretraining phase, which means that the method uses a two-phase training strategy to achieve classification. In the unsupervised pretraining phase, combined with data augmentation, positive and negative sample pairs are constructed using unlabeled ISAR images, and then the encoder is trained to learn discriminative deep representations of deformation ISAR images by means of CL. In the fine-tuning phase, based on the deep representations obtained from pretraining, a classifier is fine-tuned using a small number of labeled ISAR images, and finally, the deformation ISAR image classification is realized. In the experimental analysis, CLISAR-Net achieves higher classification accuracy than supervised learning methods for unknown scaled, rotated, and combined deformations. It implies that CLISAR-Net learned more robust deep features of deformation ISAR images through CL, which ensures the performance of the subsequent classification.

BackgroundPrimary pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare type of non-small cell lung cancer (NSCLC). Currently, anti-programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) has become an important treatment for NSCLC. Anti-human PD-1 monoclonal antibodies, such as nivolumab, significantly prolong the survival time of patients with advanced lung adenocarcinoma and lung squamous cell carcinoma. However, there are few reports on the therapeutic effect, drug resistance mechanism, and strategies to overcome resistance to anti-PD-1/PD-L1 treatment in advanced pulmonary LELC. We report the case of a patient with advanced pulmonary LELC harboring fibroblast growth factor receptor (FGFR)3 gene amplification that showed resistance to nivolumab. After treatment with anlotinib, a multi-targeted small-molecule tyrosine kinase inhibitor, the patient’s resistance to nivolumab was reversed. She achieved long-term disease remission with a combination of anlotinib and nivolumab treatment.Case PresentationA 68-year-old woman was diagnosed with stage IVA pulmonary LELC. After multiple-line chemotherapy, her disease progressed. Since the PD-L1 expression rate of the patient was 90%, nivolumab was administered. However, the therapeutic effect of nivolumab was not ideal; the disease continued to progress, and a new cervical lymph node metastasis appeared. FGFR3 gene amplification was detected in lymph node metastasis. Based on this gene abnormality, we added anlotinib to the treatment. After two cycles of anlotinib and nivolumab, the metastatic focus of the patient was significantly reduced. The patient continued to receive this combined treatment and achieved remission for more than 15 months.ConclusionPulmonary LELC with FGFR3 gene amplification may not respond well to nivolumab monotherapy. The combination of anlotinib and nivolumab can reverse the resistance to nivolumab in pulmonary LELC with FGFR3 gene amplification.

The treatment sequence of immunotherapy (IO) and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is of great importance for the survival of non-small cell lung cancer (NSCLC) patients with EGFR sensitive mutation. Here, we reported an advanced lung adenocarcinoma case concurrent with EGFR sensitive mutation and high PD-L1 expression (>50%) that was administrated with gefitinib firstly, and then became resistant to EGFR-TKI. He received the strategy of immunity-combined chemo-radiotherapy and responded significantly. However, the disease re-progressed after 10 months. Surprisingly, the tumor re-sensitized to gefitinib for 13 months. At final, following the treatment pressure of TKI-IO combination therapy-TKI strategy, tumor clone eventually transformed into small cell lung carcinoma (SCLC). For one thing, our study provided novel approach and extended the treatment spectra of overcoming immunotherapy resistance after EGFR resistance in driver oncogene-mutated NSCLC. For another thing, our case is the first time to report that SCLC transformation can be achieved after gefitinib–pembrolizumab–gefitinib resistance in EGFR sensitive mutation NSCLC, providing a new condition for SCLC transformation.

Abstract Background Zoledronic acid is the most potent osteoclast inhibitor and is widely used for advanced cancer patients with bone metastasis, but its role on cancer stem cells (CSCs) remains unclear. In the present study, we aimed to identify the stemness phenotypic characteristics of CSCs derived from cervical cancer cells and explore the anti-cancer efficiency of zoledronic acid on these cells, as well as the possible molecular mechanisms. Methods Stemness phenotypic identification of cervical cancer cells derived CSCs was performed via sphere formation efficiency (SFE), tumorigenesis, immunofluorescence staining, Transwell assay, and western blot. Anti-cancer efficiency of zoledronic acid on these cells (including proliferation, stemness phenotype, apoptosis, and cell cycle) was carried out through MTT assay, SFE, transwell, DAPI staining, flow cytometry, immunofluorescence, TUNEL staining, and western blot, both in vitro and in vivo. Results Enhanced self-renewal ability, including SFE and tumorigenesis, was verified in cervical cancer cells derived CSCs compared to parental cervical cancer cells. Specifically, the expression of ALDH1, Sox2, CD49f, Nanog, and Oct4 was significantly up-regulated in cervical cancer cells derived CSCs. Furthermore, enhanced migratory ability was observed in these cells along with up-regulated N-cadherin and Vimentin and down-regulated E-cadherin. Zoledronic acid inhibited cervical cancer cells derived CSCs proliferation in vitro and in vivo. The stemness phenotype of these CSCs including tumor sphere formation, migration, as well as the expression of the aforementioned associated markers was also suppressed. In addition, zoledronic acid significantly induced apoptosis and cell cycle arrest of cervical cancer cells derived CSCs in a dose-dependent manner. Mechanistically, the expression of phosphorylated Erk1/2 and Akt was significantly increased in cervical cancer cells derived CSCs compared to parental cervical cancer cells. Zoledronic acid inhibited phosphorylated Erk1/2 and Akt in cervical cancer cells derived CSCs. IGF-1, a potent stimulator for Erk1/2 and PI3K/Akt, attenuated the aforementioned anti-cancer effect of zoledronic acid. Conclusions Zoledronic acid inhibited the growth of cervical cancer cells derived CSCs through attenuating their stemness phenotype, inducing apoptosis, and arresting cell cycle. The suppression of phosphorylated Erk1/2 and Akt was involved in this process.

For the geosynchronous-low earth orbit (GEO-LEO) bi-static multi-channel high-resolution and wide-swath synthetic aperture radar (HRWS SAR) system, a novel azimuth Doppler signal reconstruction algorithm is developed based on an equivalent baseline approximating in the azimuth Doppler chirp Fourier transform domain. The main difficulty for the GEO-LEO bistatic multi-channel HRWS SAR system is that the baseline is variant with the scene in the conventional Doppler Fourier transform domain during azimuth signal reconstruction. The developed approach first employs the linear range cell migration correction and chirp Fourier transform to obtain the coarse-focused ambiguity SAR image. More importantly, the baseline component can be approximated a uniform baseline length for the whole image scene and the ambiguous Doppler spectrum can be reconstructed using the available Doppler signal reconstruction approach. Finally, the experimental results for a simulation GEO-LEO bi-static multi-channel HRWS SAR system are employed to validate the theoretical investigations and the proposed approach.

The Gaofen-3 (GF-3) satellite can provide digital elevation model (DEM) data from its interferogram outputs. However, the accuracy of these data cannot be ensured without applying a surveying and mapping (SAM) calibration process, thus necessitating geometric and interferometric calibration technologies. In this paper, we propose an independent parameter decomposition (IPD) method to conduct SAM calibration on GF-3 data and generate high-accuracy DEMs. We resolved the geometric parameters to improve the location accuracy and resolved the interferometric parameters to improve the height accuracy. First, we established a geometric calibration model, analyzed the Range–Doppler (RD) model and resolved the initial imaging time error as well as the initial slant range error. Then, we established a three-dimensional reconstruction (TDR) model to analyze the height error sources. Finally, the interferometric phase error and baseline vector error were precisely estimated to ensure the vertical accuracy of the interferometric results by establishing the interferometric calibration model. We then used the GF-3 interferometric data derived on the same orbit in a north–south distribution to conduct the calibration experiment. The results show that the plane positioning accuracy was 5.09 m following geometric calibration, that the vertical accuracy of the interferometric results was 4.18 m following interferometric calibration and that the average absolute elevation accuracy of the derived DEM product was better than 3.09 m when using the GF-3 SAR data, thus confirming the correctness and effectiveness of the proposed GF-3 IPD calibration method. These results provide a technical basis for SAM calibration using GF-3 interferograms at the 1:50,000 scale in China.

Sesame (Sesamum indicum L.) is an important and ancient oilseed crop. Sesame seed coat color is related to biochemical functions involved in protein and oil metabolism, and antioxidant content. Because of its complication, the genetic basis of sesame seed coat color remains poorly understood. To elucidate the factors affecting the genetic architecture of seed coat color, 366 sesame germplasm lines were evaluated for seed coat color in 12 environments. The genome-wide association studies (GWAS) for three seed coat color space values, best linear unbiased prediction (BLUP) values from a multi-environment trial analysis and principal component scores (PCs) of three seed coat color space values were conducted. GWAS for three seed coat color space values identified a total of 224 significant single nucleotide polymorphisms (SNPs, P < 2.34×10-7), with phenotypic variation explained (PVE) ranging from 1.01% to 22.10%, and 35 significant SNPs were detected in more than 6 environments. Based on BLUP values, 119 significant SNPs were identified, with PVE ranging from 8.83 to 31.98%. Comparing the results of the GWAS using phenotypic data from different environments and the BLUP values, all significant SNPs detected in more than 6 environments were also detected using the BLUP values. GWAS for PCs identified 197 significant SNPs, and 30 were detected in more than 6 environments. GWAS results for PCs were consistent with those for three color space values. Out of 224 significant SNPs, 22 were located in the confidence intervals of previous reported quantitative trait loci (QTLs). Finally, 92 candidate genes were identified in the vicinity of the 4 SNPs that were most significantly associated with sesame seed coat color. The results in this paper will provide new insights into the genetic basis of sesame seed coat color, and should be useful for molecular breeding in sesame.

Integrated with the array technique, multi-channel processing can be applied to synthetic aperture radar of ground moving target imaging (SAR GMTIm), which is very powerful in remote sensing of smart city. To reduce the data sampling amounts, compressive sensing can be used by exploiting a sparse prior of moving targets. In this paper, the SAR GMTIm from data of compressive sampling is addressed by proposing a novel reweighted sparse algorithm. Here, we mainly focus on sparse imaging and clutter suppression for heterogeneous scene of urban areas. In the scheme, the phase of interferogram and the magnitude after displaced phase center antenna are incorporated to derive the weights on sparsity-constraint. Due to the joint usage of magnitude and phase, the proposed reweighted sparse algorithm can improve the performance of clutter suppression. Finally, experiments using the simulated and measured data are performed to confirm the effectiveness of the proposed algorithm.

Using the array technique, the multi-channel synthetic aperture radar (SAR) has the capability of high-resolution imaging, detection, and location of the ground moving targets, which is a powerful tool during the remote sensing of smart city. Recently, the theory of compressive sensing has been applied to radar imaging with data of compressive sampling, which can effectively reduce the burden of current radar system. In this paper, we focus on SAR moving targets imaging from sparse aperture (SA) data with accurate target motion compensation. The procedure of motion compensation is decomposed into two steps: the SPECAN processing in the range frequency and azimuth time domain is first applied and then followed by the residue component correction embedded into sparse imaging. To overcome the SA and target motion, a novel parametric sparse imaging approach is proposed by addressing the problems of Doppler ambiguity and phase errors. In the scheme, a parametric and dynamic dictionary is used to include these two important issues. Then, a modified orthogonal matching pursuit method is presented for high-quality imaging with Doppler ambiguity number estimation and phase error correction, which can deal with the case of multiple moving targets. Finally, experimental analysis is performed to confirm the effectiveness of the proposed algorithm.

Three-dimensional (3D) triangulation based on active binocular vision has increasing amounts of applications in computer vision and robotics. An active binocular vision system with non-fixed cameras needs to calibrate the stereo extrinsic parameters online to perform 3D triangulation. However, the accuracy of stereo extrinsic parameters and disparity have a significant impact on 3D triangulation precision. We propose a novel eye gaze based 3D triangulation method that does not use stereo extrinsic parameters directly in order to reduce the impact. Instead, we drive both cameras to gaze at a 3D spatial point P at the optical center through visual servoing. Subsequently, we can obtain the 3D coordinates of P through the intersection of the two optical axes of both cameras. We have performed experiments to compare with previous disparity based work, named the integrated two-pose calibration (ITPC) method, using our robotic bionic eyes. The experiments show that our method achieves comparable results with ITPC.

The concentrations of dissolved organic carbon (DOC) and its light-absorbing fraction (chromophoric dissolved organic matter; CDOM) in surface waters, particularly those draining organic-rich peatlands, have dramatically increased over the past decade due to climate change and human disturbance. To explore the spatiotemporal dynamics of DOC and CDOM in surface waters of the northeastern Qinghai-Tibetan Plateau, we collected water samples from two rivers in the Zoige alpine wetland and from two rivers in its adjacent alpine-gorge region, during wet and dry seasons. DOC concentration ranged from 4.82 mg·L−1 to 47.83 mg·L−1, with a mean value of 15.04 mg·L−1, 2.84 times higher than the global average. The Zoige rivers had higher DOC concentration and highly terrigenous CDOM. Significantly higher DOC concentration was observed for the Zoige rivers in the wet season compared to the dry season. In contrast, the alpine-gorge rivers had higher DOC levels in the dry season. No significant correlations were observed between DOC and CDOM at all rivers due to the influence of autochthonous sources on the alpine-gorge rivers and intensive photochemical degradation of terrigenous DOM in the Zoige rivers. Significant relationships between CDOM and specific ultraviolet absorbance at 254 nm (SUVA254) and between CDOM/DOC and SUVA254 were observed, indicating that the aromaticity of DOM in the rivers was mainly determined by CDOM. Moreover, the DOC/CDOM properties of the Hei River indicate critical human-induced water quality degradation. High DOC level and high browning degree were found in rivers in the Zoige alpine wetland, indicating that large amounts of terrigenous DOC were released to the aquatic systems of the region.

Several glaciers in the Bukatage Massif are surge-type. However, previous studies in this region focused on glacier area and length changes, and more information is needed to support the deep analysis of glacier surge. We determined changes in glacier thickness, motion, and surface features in this region based on TanDEM-X, ALOS/PRISM, Sentinel-1A, and Landsat images. Our results indicated that the recent surge of the Monomah Glacier, the largest glacier in the Bukatage Massif, started in early 2009 and ceased in late 2016. From 2009 to 2016, its area and length respectively increased by 6.27 km2 and 1.45 km, and its ice tongue experienced three periods of changes: side broadening (2009−2010), rapid advancing (2010−2013), and slow expansion (2013−2016). During 2000−2012, its accumulation zone was thinned by 50 m, while its ice tongue was thickened by 90 m. During 2015−2017, its flow velocity reduced from 1.2 to 0.25 m/d, and the summer velocities were much higher than winter velocities. We conclude that the recent Monomah Glacier surge is thermal-controlled. The subglacial temperature rose to the pressure-melting point because of substantial mass accumulation, and then the increased basal meltwater caused the surge.

This paper introduces an X-ray reflective anode with a diamond heat buffer layer, so as to improve heat dissipation of micro-focus X-ray sources. This also aids in avoiding the destruction of the anode target surface caused by the accumulation of heat generated by the electron beam bombardment in the focal spot area. In addition to the description of the production process of the new reflective anode, this study focuses more on the research of the thermal conductivity and compounding ability. This paper also introduces a method that combines finite element analysis (FEA) in conjunction with thermal conductivity experiments, and subsequently demonstrates the credibility of this method. It was found that due to diamonds having a high thermal conductivity and melting point, high heat flux produced in the micro-focus spot region of the anode could be conducted and removed rapidly, which ensured the thermal stability of the anode. Experiments with the power parameters of the radiation source were also completed and showed an improvement in the power limit twice that of the original.

The characterization of genetic diversity and population structure can be used in tandem to detect reliable phenotype–genotype associations. In the present study, we genotyped a set of 366 sesame germplasm accessions by using 89,924 single-nucleotide polymorphisms (SNPs). The number of SNPs on each chromosome was consistent with the physical length of the respective chromosome, and the average marker density was approximately 2.67 kb/SNP. The genetic diversity analysis showed that the average nucleotide diversity of the panel was 1.1 × 10-3, with averages of 1.0 × 10-4, 2.7 × 10-4, and 3.6 × 10-4 obtained, respectively for three identified subgroups of the panel: Pop 1, Pop 2, and the Mixed. The genetic structure analysis revealed that these sesame germplasm accessions were structured primarily along the basis of their geographic collection, and that an extensive admixture occurred in the panel. The genome-wide linkage disequilibrium (LD) analysis showed that an average LD extended up to ∼99 kb. The genetic diversity and population structure revealed in this study should provide guidance to the future design of association studies and the systematic utilization of the genetic variation characterizing the sesame panel.

A good genetic map can provide the framework for quantitative trait loci (QTL) analysis, map-based gene cloning, and genome sequence assembling. The main objectives of this study were to develop a high-density genetic linkage map using specific length amplified fragment sequencing (SLAF-seq) in sesame. In the result, a high-resolution genetic map with 9,378 SLAF markers and 13 linkage groups (LGs) was constructed. The map spanned a total genetic distance of 1,974.23 cM, and the mean LG length was 151.86 cM, with an average genetic distance of 0.22 cM between adjacent markers. Based on the newly constructed genetic map, genes for basal branching habit (SiBH) and flowers per leaf axil (SiFA) were mapped to LG5 and LG11, respectively.

Therapy advances are constantly improving survival rates of cancer patients, however the toxic effects of chemotherapy drugs can seriously affect patients' quality of life. In women, fertility and premature ovarian endocrine dysfunction are of particular concern. It is urgently we find methods to preserve or reconstruct ovarian function for these women. This study compares GnRHa treatment with ovarian tissue cryopreservation and orthotopic transplantation in a chemotherapy-induced ovarian damage murine model. 56 inbred Lewis rats were divided into 4 treatment groups: Saline control (group I); cyclophosphamide only (group II); cyclophosphamide plus GnRHa (group III); cyclophosphamide and grafting of thawed cryopreserved ovaries (group IV). Body weight, estrous cycle recovery time, ovarian weight, morphology and follicle count, as well as breeding and fertility were compared among groups. Only group IV was able to restore to normal body weight by the end of the observation period and resumed normal estrous cycles in a shorter time compared to other treatment groups. There was a decrease in primordial follicles in all treatment groups, but group III had the greatest reduction. Although, there was no difference in pregnancy, only one animal littered normal pups in group II, none littered in group III and four littered in group IV. Thus, cryopreservation and orthotopic transplantation of ovarian tissue can restore the fertility of rats subjected to chemotherapy in a manner that is superior to GnRHa treatment. We also observed increased rates of hepatic, splenic and pulmonary haemorrhage in group III, suggesting there may be synergistic toxicity of GnRHa and cyclophosphamide.

Targeted therapy and immunotherapy are both important in the treatment of non-small-cell lung cancer (NSCLC). Accurate diagnose and precise treatment are key in achieving long survival of patients. MET fusion is a rare oncogenic factor, whose optimal detection and treatment are not well established. Here, we report on a 32-year-old female lung adenocarcinoma patient with positive PD-L1 and negative driver gene detected by DNA-based next-generation sequencing (NGS). A radical resection of the primary lesion after chemotherapy combined with PD-1 checkpoint inhibitor administration indicated primary immunoresistance according to her pathological response and rapid relapse. A rare CD47-MET was detected by RNA-based NGS, which was confirmed by fluorescence in situ hybridization. Multiplex immunofluorescence revealed a PD-L1 related heterogeneous immunosuppressive microenvironment with little distribution of CD4+ T cells and CD8+ T cells. Savolitinib therapy resulted in a progression-free survival (PFS) of >12 months, until a new secondary resistance mutation in MET p.D1228H was detected by re-biopsy and joint DNA-RNA-based NGS after disease progression. In this case, CD47-MET fusion NSCLC was primarily resistant to immunotherapy, sensitive to savolitinib, and developed secondary MET p.D1228H mutation after targeted treatment. DNA-RNA-based NGS is useful in the detection of such molecular events and tracking of secondary mutations in drug resistance. To this end, DNA-RNA-based NGS may be of better value in guiding precise diagnosis and individualized treatment in this patient population. [ABSTRACT FROM AUTHOR]