Search

Abstract The increasing incidence of autism spectrum disorder (ASD) worldwide poses serious social and family problems. Various risk factors for ASD are gradually being recognized, and there are also various options for the treatment of ASD. It is worth noting that dietary interventions have been shown to have a positive effect in terms of mitigating and preventing some psychiatric disorders, such as epilepsy, Parkinson's disease, and ASD, and they are gradually receiving attention as a safe adjuvant treatment. In this review, based on the current understanding of the pathogenic factors and intervention strategies for ASD, different dietary patterns that can be selected for children with ASD are discussed in depth. Moreover, a review was conducted on the use of dietary factors, such as natural products from food sources, prebiotics, and probiotics, as effective supplements to existing dietary patterns. As increasing evidence shows that maternal risk factors, such as obesity, diabetes, and hypertension, are associated with an increased risk of ASD in offspring, dietary suggestions are also made for pregnant woman with ASD‐related risk factors to counteract the impact of these risk factors. With compensation from food‐derived natural products, prebiotics, and probiotics, suitable dietary patterns can further enhance the effectiveness of dietary interventions for ASD. In addition, dietary recommendations for pregnant woman may reduce the potential impact of obesity, diabetes, and hypertension and may help to prevent the occurrence of ASD to the maximum extent possible.

Abstract Objective It has been observed that the prognosis of patients with HER2‐positive metastatic breast cancer has improved significantly with HER2‐targeted agents. However, there is still a lack of evidence regarding first‐line anti‐HER2 treatment options for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2‐positive metastatic breast cancer. Besides, there are no reliable markers that can predict the efficacy of anti‐HER2 treatment in these patients. Methods Patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2‐positive metastatic breast cancer were enrolled. Pyrotinib plus albumin‐bound paclitaxel were used as first‐line treatment. The primary endpoint was the objective response rate (ORR). The safety profile was also assessed. In order to explore predictive biomarkers using Olink technology, blood samples were collected dynamically. Results From December 2019 to August 2023, the first stage of the study involved 27 eligible patients. It has not yet reached the median PFS despite the median follow‐up being 17.8 months. Efficacy evaluation showed that the ORR was 92.6%, and the DCR was 100%. Adverse events of grade 3 or higher included diarrhoea (29.6%), leukopenia (11.1%), neutropenia (25.9%), oral mucositis (3.7%), and hand‐foot syndrome (3.7%). Toll‐like receptor 3 (TLR3) and Proto‐oncogene tyrosine‐protein kinase receptor (RET) were proteins with significant relevance to PFS in these patients. Conclusions This study demonstrates that pyrotinib plus albumin‐bound paclitaxel as a first‐line treatment regimen shows good efficacy and manageable safety for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2‐positive metastatic breast cancer. Besides, a significant association was identified between the expression levels of TLR3 and RET and the PFS in patients.

Abstract Anti‐virulence therapy that interferes with bacterial communication, known as “quorum sensing (QS)”, is a promising strategy for circumventing bacterial resistance. Using nanomaterials to regulate bacterial QS in anti‐virulence therapy has attracted much attention, which is mainly attributed to unique physicochemical properties and excellent designability of nanomaterials. However, bacterial QS is a dynamic and multistep process, and there are significant differences in the specific regulatory mechanisms and related influencing factors of nanomaterials in different steps of the QS process. An in‐depth understanding of the specific regulatory mechanisms and related influencing factors of nanomaterials in each step can significantly optimize QS regulatory activity and enhance the development of novel nanomaterials with better comprehensive performance. Therefore, this review focuses on the mechanisms by which nanomaterials regulate bacterial QS in the signal supply (including signal synthesis, secretion, and accumulation) and signal transduction cascade (including signal perception and response) processes. Moreover, based on the two key influencing factors (i.e., the nanomaterial itself and the environment), optimization strategies to enhance the QS regulatory activity are comprehensively summarized. Collectively, applying nanomaterials to regulate bacterial QS is a promising strategy for anti‐virulence therapy. This review provides reference and inspiration for further research on the anti‐virulence application of nanomaterials.

The rapid advancement of mobile devices and human–machine interaction technologies has ushered in a new era for flexible touch panels as a novel input interface. This article reviews the historical evolution and technical progress of flexible touch panel technologies, from rudimentary single‐point touch to sophisticated grid‐free touch systems. Additionally, the working principles and mechanisms that underpin these advanced systems, including capacitive, resistive, piezoelectric, and triboelectric nanogenerator technologies, are explored. Following this, the integration of machine learning methods into these panels is discussed, offering new avenues for enhancing user experience and expanding functional capabilities. Various machine learning algorithms such as support vector machines, artificial neural networks, convolutional neural networks, and k‐nearest neighbors are examined for their potential applications in touch panel technologies. Finally, the challenges and prospects for the application of flexible touch panels fused with machine learning are discussed.

Abstract Background Immune checkpoint inhibitors (ICIs) combined with chemotherapy have been recommended as the standard treatment for advanced NSCLC patients without driver‐gene mutations. However, there are different genetic characteristics and biological traits of tumors between non‐East Asian (nEA) and East Asian (EA) patients with NSCLC, which may contribute to differences in the efficacy of ICIs in different ethnic populations. Previous findings regarding differences in the efficacy of ICIs among ethnic groups have been inconsistent. Therefore, we performed a meta‐analysis by collecting published data to investigate the clinical outcomes of ICIs for EA NSCLC patients compared to nEA patients. Methods Overall survival (OS) and progression‐free survival (PFS) were used to access the difference in survival outcomes between the two populations. Subgroup analyses were performed based on the line of ICIs, the use of ICIs alone or in combination, and the type of ICIs. Results A total of 9826 NSCLC patients from 21 randomized controlled trials (RCTs) with 4064 EAs were included, which involved PD‐1, PD‐L1, and CTLA‐4 inhibitors. EA NSCLC patients who received ICIs‐based therapy were associated with significantly improved survival benefits in OS (p = 0.02) compared with nEA patients. Subgroup analysis indicated that EA patients receiving first‐line ICIs showed significantly superior OS compared with nEA patients (p = 0.007). Chemo‐ICIs treatment showed significant advantages in terms of OS (p = 0.002) and PFS (p = 0.02) among EA patients compared to nEA patients. In addition, PD‐1 inhibitors were associated with improved OS among both EA patients and nEA patients compared with PD‐L1 inhibitors. Conclusion EA NSCLC patients who received ICIs‐based therapy were associated with significantly improved survival benefits compared with nEA NSCLC patients. Earlier intervention with ICIs and combination treatment was more recommended for EA NSCLC patients. Moreover, PD‐1 inhibitors are associated with prolonged survival among both EA and nEA patients.

Abstract Aqueous zinc (Zn) ion batteries (AZIBs) have not yet fulfilled their talent of high safety and low cost since the anode/electrolyte interface (AEI) has long been impeded by hydrogen evolution, surface corrosion, dendritic growth, and by‐product accumulation. Here, the hydrolysis of solid buffers is elaborately proposed to comprehensively and enduringly handle these issues. Take 2D layered black phosphorus (BP) as a hydrolytic subject. It is reported that the phosphoric acid generated by hydrolysis in an aqueous electrolyte produces a zinc phosphate (ZPO) rich solid electrolyte interphase (SEI) layer, which largely inhibits the dendrite growth, surface corrosion, and hydrogen evolution. Meanwhile, the hydrolytic phosphoric acid stabilizes the pH value near AEI, avoiding the accumulation of alkaline by‐products. Notably, compared with the disposable ZPO engineerings of anodic SEI pre‐construction and electrolyte additive, the hydrolysis strategy of BP can realize a dramatically prolonged protective effect. As a result, these multiple merits endow BP modified separator to achieve improved stripping/plating stability toward Zn anode with more than ten times lifespan enhancement in Zn||Zn symmetrical cell. More encouragingly, when coupled with a V2O5·nH2O cathode with ultra‐high loadings (34.1 and 28.7 mg cm−2), the cumulative capacities are remarkably promoted for both coin and pouch cells.

Abstract Joint time–frequency analysis is an emerging method for interpreting the underlying physics in fuel cells, batteries, and supercapacitors. To increase the reliability of time–frequency analysis, a theoretical correlation between frequency‐domain stationary analysis and time‐domain transient analysis is urgently required. The present work formularizes a thorough model reduction of fractional impedance spectra for electrochemical energy devices involving not only the model reduction from fractional‐order models to integer‐order models and from high‐ to low‐order RC circuits but also insight into the evolution of the characteristic time constants during the whole reduction process. The following work has been carried out: (i) the model‐reduction theory is addressed for typical Warburg elements and RC circuits based on the continued fraction expansion theory and the response error minimization technique, respectively; (ii) the order effect on the model reduction of typical Warburg elements is quantitatively evaluated by time–frequency analysis; (iii) the results of time–frequency analysis are confirmed to be useful to determine the reduction order in terms of the kinetic information needed to be captured; and (iv) the results of time–frequency analysis are validated for the model reduction of fractional impedance spectra for lithium‐ion batteries, supercapacitors, and solid oxide fuel cells. In turn, the numerical validation has demonstrated the powerful function of the joint time–frequency analysis. The thorough model reduction of fractional impedance spectra addressed in the present work not only clarifies the relationship between time‐domain transient analysis and frequency‐domain stationary analysis but also enhances the reliability of the joint time–frequency analysis for electrochemical energy devices.

Abstract Objectives Anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK TKIs) have shown remarkable clinical activity in patients with non‐small‐cell lung cancer (NSCLC). However, pneumonitis is a serious side effect of ALK TKIs in NSCLC patients. In this meta‐analysis, we aimed to determine the incidence of ALK‐TKI‐associated pneumonitis. Materials and Methods We searched electronic databases to identify relevant studies published until August 2022. The incidence of pneumonitis was calculated using a fixed‐effects model when no substantial heterogeneity was observed. Otherwise, a random‐effects model was used. Subgroup analyses of different treatment groups were performed. Statistical analyses were conducted using STATA 17.0. Results Twenty‐six clinical trials involving 4752 patients were eligible for analysis. All‐grade pneumonitis incidence was 2.92% (95% confidence interval [CI]: 1.79%–4.27%), high‐grade (Grade 3–4) pneumonitis incidence was 1.42% (95% CI: 0.84%–2.12%) and Grade 5 pneumonitis incidence was 0.09% (95% CI: 0.00%–0.28%). The subgroup analysis showed that brigatinib was associated with the highest incidence of both all‐grade and high‐grade pneumonitis (7.09% and 3.06%, respectively). ALK TKI treatment after chemotherapy was associated with a higher incidence of all‐grade and high‐grade pneumonitis than first‐line ALK TKI treatment (7.73% vs. 2.26% and 3.64% vs. 1.26%, respectively). Cohorts from Japanese trials had a higher incidence of all‐grade and high‐grade pneumonitis. Conclusion Our study provides precise data on the incidence of pneumonitis in patients receiving treatment with ALK TKIs. Overall, ALK TKIs have tolerable pulmonary toxicity. Early pneumonitis identification and treatment are required to prevent further deterioration in patients receiving treatment with brigatinib and in those who received prior chemotherapy, particularly in the Japanese population.

Abstract Introduction Pulmonary infections are frequent in immunocompromised hosts (ICH), and microbial detection is difficult. As a new method, next‐generation sequencing (NGS) may offer a solution. Objectives This study aimed to assess the impact of NGS‐assisted pathogenic detection on the diagnosis, treatment, and outcomes of ICH complicated by pulmonary infection and radiographic evidence of bilateral diffuse lesions. Methods This study enrolled 356 patients with ICH complicated by pulmonary infection that were admitted to Zhongshan Hospital, Fudan University, from November 17, 2017, to November 23, 2018, including 102 and 254 in the NGS and non‐NGS groups, respectively. Clinical characteristics, detection time, rough positive rate, effective positive rate, impact on anti‐infective treatment plan, 30‐day/60‐day mortality, and in‐hospital mortality were compared. Results NGS‐assisted pathogenic detection reduced detection time (28.2 h [interquartile range (IQR) 25.9–29.83 h] vs. 50.50 h [IQR 47.90–90.91 h], P

Abstract Background Accurate prognostic prediction plays a crucial role in the clinical setting. However, the TNM staging system fails to provide satisfactory individual survival prediction for stage III non‐small cell lung cancer (NSCLC). The performance of the deep learning network for survival prediction in stage III NSCLC has not been explored. Objectives This study aimed to develop a deep learning‐based prognostic system that could achieve better predictive performance than the existing staging system for stage III NSCLC. Methods In this study, a deep survival learning model (DSLM) for stage III NSCLC was developed based on the Surveillance, Epidemiology, and End Results (SEER) database and was independently tested with another external cohort from our institute. DSLM was compared with the Cox proportional hazard (CPH) and random survival forest (RSF) models. A new prognostic system for stage III NSCLC was also proposed based on the established deep learning model. Results The study included 16,613 patients with stage III NSCLC from the SEER database. DSLM showed the best performance in survival prediction, with a C‐index of 0.725 in the validation set, followed by RSF (0.688) and CPH (0.683). DSLM also showed C‐indices of 0.719 and 0.665 in the internal and real‐world external testing datasets, respectively. In addition, the new prognostic system based on DSLM (AUROC = 0.744) showed better performance than the TNM staging system (AUROC = 0.561). Conclusion In this study, a new, integrated deep learning‐based prognostic model was developed and evaluated for stage III NSCLC. This novel approach may be valuable in improving patient stratification and potentially provide meaningful prognostic information that contributes to personalized therapy.

Abstract Introduction Acute respiratory distress syndrome (ARDS) is characterized by hypoxemia and increased lung permeability and would result in acute respiratory failure and with high mortality. In patients who survive from acute lung injury (ALI)/ARDS, it is an active process of the transition from injury to resolution depending on the coordinated immune system. The roles of regulatory CD4+T cells (Tregs) are now gradually being clarified during inflammation and resolution of ARDS. However, clear conclusions about roles of Tregs in ALI/ARDS are only a few. Objective This review provides an overview of phenotype, differentiation, and suppressive mechanisms of Tregs and focuses on keys of biology of Tregs in alveolar space during the inflammatory response and resolution of ALI/ARDS. Data Source Literature search of Web of Science, PubMed, and EMBASE was made to find relative articles about Tregs in ALI/ARDS. We used the following search terms: Tregs, ALI, ARDS, inflammation, and resolution. Conclusion More and more studies have indicated Tregs involved in the processes of inflammation and resolution of ALI/ARDS. A deep understanding of the roles of Tregs may indicate new treatments for patients of ARDS. Therapies aimed at expansion or adaptive transfer of Tregs could be an effective therapy to ARDS patients.

Abstract Background The current study aimed to comprehensively analyze the clinical prognostic factors of malignant esophageal fistula (MEF). Furthermore, this study sought to establish and validate prognostic nomograms incorporating radiomics and clinical factors to predict overall survival and median survival after fistula for patients with MEF. Methods The records of 76 patients with MEF were retrospectively analyzed. A stepwise Cox proportional hazards regression model was employed to screen independent prognostic factors and develop clinical nomograms. Radiomic features were extracted from prefistula CT images and post fistula CT images. Least absolute shrinkage and selection operator (LASSO) regression and Cox regression algorithm was used to filter radiomic features and avoid overfitting. Radiomic signature was a linear combination of optimal features and corresponding coefficients. The joint prognostic nomograms was constructed by radiomic signatures and clinical features. All models were validated by Harrell's concordance index (C‐index), caliberation and bootstrap validation. Results For overall survival, age, prealbumin, KPS and interval between diagnosis of esophageal cancer and fistula were identified as independent prognostic factors and incorporated into the clinical nomogram. Age, prealbumin, serum albumin, KPS and neutrophil proportion were selected for the clinical nomogram of post fistula survival. The C‐index of overall survival nomogram was 0.719 (95% CI: 0.645–0.793) and that was 0.722 (95% CI: 0.653–0.791) in the post fistula survival nomogram. The radiomic signature developed by radiomic features of prefistula CT showed a significant correlation with both overall survival and post fistula survival. The C‐index of joint nomogarm for overall survival and post fistula survival was 0.831 (95% CI: 0.757–0.905) and 0.77 (95% CI: 0.686–0.854), respectively. The calibration curve showed the joint nomograms outperformed the clinical ones. Conclusions The study presents nomograms incorporating independent clinical risk factors and radiomic signature to predict the prognosis of MEF. This prognostic classification system has the potential to guide therapeutic decisions for patients with malignant esophageal fistulas.

Objectives. This study aimed to analyze the clinical features, antibiotic susceptibility profiles, and outcomes of patients with invasive pneumococcal disease (IPD) at a hospital in Ningxia Hui Autonomous Region, to provide the basis for improving the clinical treatment effect. Methods. Patients with IPD were retrospectively collected from 2013 to 2021. Clinical manifestations, laboratory tests, antimicrobial susceptibility, antibiotic treatment, and outcomes of the disease were analyzed. Results. In this study, we identified 127 IPD cases, of whom 49 (38.6%) had meningitis and 78 (61.4%) had bacteremia. The median ages of pediatric cases and adult cases were 2 years (IQR: 0–5) and 52.5 years (IQR: 35–62), respectively. There were 27 and 45 males in the pediatric and adult groups, and no significant gender difference in the different age groups (p=0.584) was found. Of 75 cases with underlying diseases, pneumonia (11%), malignancy (11%), hypertension (9.4%), and hepatic cirrhosis (7.9%) were the most common. The incidence of underlying diseases was even higher in the adult group (67.1%) than in the pediatric group (47.1%) (p=0.028). The frequency of fever, cough, and seizures was significantly higher in the pediatric group than in the adult group, with p-values of 0.004, 0.004, and 0.001, respectively. The percentage of neutrophils in the blood was significantly higher in the adult cases than in the pediatric cases (p

Abstract Green tea, superfine green tea powder (SGTP), and tea extract were prepared to determine their chemical components and antioxidant activity. The nutrition and aroma challenges of green tea during traditional extract technique and superfine grinding were profiled in this study. The traditional extract technique took advantage over superfine grinding in L‐theanine and glutamic acid (Glu) preservation, but not in other 16 essential amino acids. SGTP preserved a maximum of elements from green tea, whereas tea extract greatly changed the elements ratio. Tea extract contained higher VB2 and VC contents and doubled the tea polyphenol (TP) content in comparison with green tea and SGTP. Additionally, tea extract contained more favorable aroma compounds and maintained stronger antioxidant activity in comparison with green tea and SGTP. This study profiled an important basis for the comprehensive utilization of green tea resources by consumers and manufacturers.

Abstract This study was investigated the effects of six proteases (papain, compound proteinase, acidic protease, neutrase, pancreatin, and alcalase) on the lipid yield and quality of krill oil. The result shown that the krill oil extracted by alcalase and compound proteinase led to comparatively higher lipid yields (5.29% and 4.90%, respectively), Content of tocopherols and vitamin A, the content of omega‐3 polyunsaturated fatty acids (PUFAs) and phospholipids extracted by alcalase was relatively higher. Control and alcalase had comparatively higher concentration of astaxanthin. On the whole, compared with the extraction of solvent, enzymatic hydrolysis could improve the quality and the lipid yield of krill oil. Therefore, enzymatic hydrolysis could be used as a better method to extract krill oil.

Abstract Introduction Locally advanced nonsmall‐cell lung cancer (LA‐NSCLC) represented a highly heterogeneous group, with more than half of the patients aged ≥65 years at the time of diagnosis. However, the optimal treatment for elderly LA‐NSCLC patients was still not defined. Methods A total of 33530 elderly patients (≥65 years) diagnosed with LA‐NSCLC from 2004 to 2014 were identified from Surveillance, Epidemiology, and End Results (SEER) database. Results Locally advanced nonsmall‐cell lung cancer patients aged 65‐74 years were more frequently treated with chemoradiotherapy (CRT) (40%), while patients aged ≥75 years received more best supportive care (BSC) (36%). For age group of 65‐74 years, patients who had surgery with or without (neo)adjuvant therapy had a median survival of 28 months, CRT 15 months, radiotherapy (RT) alone 6 months, chemotherapy alone 11 months, and BSC 3 months; while for patients aged ≥ 75 years, the median OS was 20, 13, 7, 9, and 2, respectively. Besides, independent clinicopathological factors were integrated into nomograms for OS and CSS prediction, C‐indexes achieved 0.692 and 0.698, respectively. Importantly, the discrimination of nomogram was superior to that of the American Joint Committee on Cancer TNM classification (0.742 vs 0.572 for training set and 0.731 vs 0.565 for validation set). Conclusion For elderly patients with LA‐NSCLC, the curative‐intent treatment (surgery or CRT) conferred better survival compared to chemotherapy alone, RT alone and BSC. The proposed nomograms based on independent clinicopathological variables may be practical and helpful for precise evaluation of patient prognosis, and guiding the individualized treatment for elderly LA‐NSCLC.

Separation power was limited when the conventional high-performance liquid chromatography (HPLC) fingerprinting method based on a single column was used to analyze very complex traditional Chinese medicine (TCM) preparations. In this research, a novel HPLC fingerprinting method based on column switching technology by using a single pump was established for evaluating the quality of Tianmeng oral liquid (TMOL). Twelve batches of TMOL samples were used for constructing HPLC fingerprints. Compared with the 16 common peaks in fingerprinting with a single column, 25 common peaks were achieved with two columns connected through a six-way valve. The similarity analysis combined with bootstrap method was applied to determine the similarity threshold, which was 0.992 to distinguish expired samples and unexpired samples. Principal component analysis (PCA) and hierarchical clustering analysis (HCA) were also applied to classify the TMOL samples, and results revealed that expired and unexpired samples are classified into two categories. The HPLC fingerprinting based on column switching technology with better separation power and higher peak capacity could characterize chemical composition information more comprehensively, providing an effective and alternative method to control and evaluate the quality of TMOL, which would offer a valuable reference for other TCM preparations.

The Late Permian on the periphery of the Songliao Basin, eastern Inner Mongolia, is an important hydrocarbon source rock system. Its sedimentary environment plays an important role in the evaluation of hydrocarbon prospects in the area. Unfortunately, until now, the interpretation of the sedimentary environment of this area has been controversial. We investigated the Late Permian sedimentary environment by studying the sedimentary characteristics and geochemistry. Based on these investigations, we conclude that the Linxi Formation is mainly composed of clastic sediments, interbedded with limestone lenses, with bioherm limestone at the top of the formation. Inner-layer marine fossils (calcium algae, bryozoans, and sponges) and freshwater and blackish water microfossils (bivalves) are all present, indicative of a typical shallow water sedimentary environment with an open and concussion background. In terms of geochemistry, the formation is relatively light rare Earth enriched, with significant positive Eu anomaly, slight positive La and Y anomaly, weak positive Gd anomaly, and lack of Ce anomaly. The average B/Ga ratio of the mudstone is greater than 3.3, and the average Sr/Ba ratio of the limestone is greater than 1.0. The range of the 87Sr/86Sr ratio is from 0.707285 to 0.707953. The range of δ13C values is from −4.0‰ to 2.4‰. The sediment assemblages, rare Earth elements, trace elements, and 87Sr/86Sr and C isotopes of the formation indicate that the Linxi Formation formed in a marine sedimentary environment and occasional marine-terrestrial transitional facies. The formation can be further divided into littoral facies, neritic facies, bathyal facies, and delta front.

Mesenchymal stem cells (MSCs) are being widely investigated for the development of novel therapeutic approaches for different cancers, including breast cancer, the leading form of cancer in women. Our previous study showed that the factors secreted by human umbilical cord MSCs (hUCMSCs) induced pyroptosis in the breast cancer cell line MCF7 and our RNA sequencing studies revealed an increase in the expression of the pyroptosis-related gene caspase-4 (CASP4) and nucleotide-binding, leucine-rich repeat pyrin domain-containing protein 1 (NLRP1) in pyroptotic MCF7 cells. Cellular pyroptosis can occur via the canonical pathway (involving caspase-1 and NLRP1) or the noncanonical pathway (involving caspase-4). In this study, we first confirmed that the inflammasome complex formed by NLRP1 and ASC is involved in MCF7 cell pyroptosis induced by hUCMSC-CM. Further, we investigated the role of CASP4 and NLRP1 in MCF7 cell pyroptosis induced by hUCMSC-secreted factors using shRNA-mediated transfection of CASP4 or NLRP1 in MCF7 cells. Cytotoxicity analyses revealed that neither CASP4 knockdown nor NLRP1 knockdown could inhibit the hUCMSC-CM-induced pyroptosis in MCF7 cells. Gene and protein expression analysis showed that hUCMSC-CM induced pyroptosis mainly via the canonical pathway in CASP4 knockdown MCF7 cells but mainly via the noncanonical pathway in NLRP1 knockdown MCF7 cells. Our study provides a foundation for further studies aimed at elucidating the precise mechanism underlying hUCMSC-induced pyroptosis in breast cancer cells and aid the identification of potential therapeutic targets for breast cancer.

Abstract Background Advanced ALK-rearranged non-small cell lung cancer (NSCLC) patients will develop acquired resistance after anaplastic lymphoma kinase (ALK) inhibitors therapies. Vascular endothelial growth factor-A (VEGF-A) production and tumor vessel formation were found to be more significantly enriched in ALK-rearrangement NSCLC than that in epidermal growth factor receptor or Kirsten rat sarcoma viral oncogene mutated NSCLC. However, the correlation between ALK rearrangement and the efficacy of bevacizumab (a recombinant humanized IgG1 monoclonal antibody targeting VEGF-A) was still elusive. Case presentation We report a case with metastatic NSCLC harboring ALK-rearrangement who was initially resistant to two courses of ALK-Tyrosine Kinase Inhibitor (TKI) therapy, but got a clinical benefit of 7 months of progression free survival after the combined treatment of bevacizumab plus pemetrexed. And the patient tolerated well. Conclusions It suggested that bevacizumab combined with pemetrexed might be a preferred option for ALK rearrangement patient who had failed no less than two courses of ALK-TKIs.

Abstract Dimerization of proteins occurs frequently and plays integral roles in biological processes. However, no single molecular probe is available for in situ detection of protein dimers on cells and tissues because of the difficulty of isolating complete protein dimers for probe preparation and screening, which has greatly hampered the biomedical study of protein dimers. Herein, a G‐rich DNA aptamer (termed BG2) that only binds alkaline phosphatase (AP) heterodimers rather than monomers is reported. This aptamer is generated by the cell‐SELEX (systematic evolution of ligands by exponential enrichment) technique and proves to fold into a duplex stabilized antiparallel G‐quadruplex structure. Using BG2 as molecular probe, AP heterodimers are found to be expressed on several kinds of cancer cells. As an affinity ligand, BG2 could isolate AP heterodimers from cell lysate. BG2 is also demonstrated to be applicable for tumor imaging in mice xenografted with cells highly expressing AP heterodimers. AP isozymes are found in several tissues and blood throughout the body, but the function and tissue distribution of AP heterodimers are totally unknown; therefore, BG2 could serve as a molecular probe to uncover the mystery of AP heterodimers. The generation of aptameric probes by cell‐SELEX will open up a new situation for the study of protein dimers.

In order to obtain the optimum power factor through maintaining the ratio of blade tip speed to wind speed, a new method for controller design of wind driven generator speed tracking is proposed basing on variable structure control theory. Integral variable of generator speed is introduced into the system equation. Switching surface of variable structure controller is founded with the error of generator speed. Adaptive estimation for wind disturbance and uncertain parameters of system dynamics model is adopted to derive control algorithm for rotation torque in the process of generator speed tracking. Simulation results show that speed tracking precision of wind driven generator is improved by integral variable structure controller. The method proposed in this article is effective and feasible.

Although the hydraulic fracturing treatment can improve the conductivity of shale reservoirs, the low recovery rate of the fracturing fluid may cause potential environmental and production issues. For an accurate investigation of these issues, an appropriate model of the water imbibition in shales is required. However, the hydraulic parameters related to water imbibition in shales are hard to be measured due to their tiny pores. In this study, an effective method is proposed to estimate the water imbibition volume. The nuclear magnetic resonance method is applied to obtain the related parameters including the capillary curve, the intrinsic and relative permeability of the shale, which can significantly cut down the time and cost needed to get these data. This model is validated by water imbibition experiments. In addition, we compare two empirical equations used to calculate intrinsic permeability in the NMR method and calibrate the corresponding parameter a for shale, which is poorly investigated in literature. Finally, we suggest that the capillary force dominates the early stage of water imbibition process in unsaturated shales, and the late period may be influenced more by other mechanisms such as the osmosis and the surface hydration.

The purpose of this report was to perform an experimental evaluation of enhanced oil recovery (EOR) using CO2 injection. A slim tube test and PVT experiment are used to determine the minimum miscibility pressure as well as a few related physical properties. Combined with a long core displacement experiment and nuclear magnetic resonance, CO2 flooding and CO2-water alternate flooding are simulated, and the displacement efficiency of different types of pores is evaluated. The results indicate that the minimum miscibility pressure is 32.6 MPa, and the CO2 flooding is at near-miscible conditions at the current formation pressure. The CO2 solubility of crude oil is large, and the crude oil has a strong expansion ability after the CO2 injection, which is beneficial for improving the recovery of CO2. The EOR of CO2-water alternate flooding is 3.97% higher than that of continuous CO2 flooding, and the EOR in the small and middle pores in the CO2-water alternate flooding is clearly higher. These results will be relevant for the future development of Block M.

Abstract Insufficient endogenous neurotrophin supply contributes to neurodegeneration. Meanwhile, neuronal injuries are also attributed to oxidative stress upon toxin exposure. Thus, reconstruction neurite extension and antioxidative stress are the potential strategies for ameliorating neuronal injuries. However, there is no well‐defined therapeutic developed in this regard. In search of such therapeutics, Petrosiol E is identified here as a potent inducer to guide the differentiation of neuronal progenitor cells. Petrosiol E also considerably promotes embryonic stem cell differentiation into neural ectoderm features. Moreover, Petrosiol E reveals an antioxidant function to protect cells from oxidative stress induced by arsenic. Moreover, the molecular mechanism underlying Petrosiol E‐induced neuronal differentiation is uncovered: (a) enhancement of NF‐E2‐related factor 2 (Nrf 2) activity in driving neuronal differentiation; (b) diminishment of oxidative stress. Petrosiol E activates the mitogen‐activated protein kinase and serine/threonine kinase signaling to enhance the activity of Nrf 2. As a result of enhanced Nrf 2 activity, neuronal differentiation is accelerated, and the cellular antioxidation responses are also enforced, even under arsenic‐induced neurotoxicity. Together, the combined results unveil a desirable role of Petrosiol E in driving neuronal differentiation and in combating oxidative stress. This study would open an avenue to develop new therapeutics based on Petrosiol compounds to treat neurodegenerative diseases.

This paper deals with feedback control systems on time scales. Firstly, we generalize the semicycle concept to time scales and then establish some differential inequalities on time scales. Secondly, as applications of these inequalities, we study the uniform ultimate boundedness of solutions of these systems. We give a new method to investigate the permanence of ecosystem on time scales. And some known results have been generalized. Finally, an example is given to support the result.

Generally, plant reproductive success might be affected negatively by florivory, and the effects may vary depending on the timing and intensity of florivory. To clarify the impacts of florivory by the sawfly larvae (Tenthredinidae) on seed production of Halenia elliptica D. Don, we simulated florivory by removing different proportion of flowers at three reproductive stages in this alpine herb and then examined the seed number per fruit, the seed weight, and the seed mass per fruit of the remaining flowers. Seed number per fruit reduced significantly when flowers were removed at flowering and fruiting stages or when 15% and 60% of flowers were removed. However, seed weight increased significantly after flowers were removed, independent of treatments of reproductive stage and proportion. There was a similar seed mass per fruit between the plants subjected to simulation of florivory and control. The results indicated that florivory modulated the seed number-seed weight relationship in this alpine species. Our study suggested that selective seed abortion and resource reallocation within fruits may ensure fewer but larger seeds, which were expected to be adaptive in the harsh environments.

Considering the case of ASV (autonomous surface vehicle) navigating with low speed near water surface, a new method for design of roll motion controller is proposed in order to restrain wave disturbance effectively and improve roll stabilizing performance. Control system design is based on GPC (general predictive control) theory and working principle of zero-speed fin stabilizer. Coupling horizontal motion model of ASV is decoupled, and an equivalent transfer function of roll motion is obtained and transformed into a discrete difference equation through inverse Laplace transformation and Euler approximation. Finally, predictive model of GPC, namely, the difference equation of roll motion, is given. GPC algorithm of ASV roll motion is derived from performance index based on roll stabilizing performance and energy consumption used for driving fin stabilizer. In allusion to time-variant parameters in roll motion model, recursive least square method is adopted for parameter estimation. Simulation results of ASV roll motion control show better stabilizing performance and minimized energy consumption improved by self-adaptive GPC.