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FGFR1 is a key member of the fibroblast growth factor receptor family, mediating critical signaling pathways such as RAS-MAPK and PI3K-AKT. which are integral to regulating essential cellular processes, including proliferation, differentiation, and survival. Alterations in FGFR1 can lead to constitutive activation of signaling pathways that drive oncogenesis by promoting uncontrolled cell division, inhibiting apoptosis, and enhancing the metastatic potential of cancer cells. This article reviews the activation mechanisms and signaling pathways of FGFR1 and provides a detailed exposition of the types of FGFR1 aberration. Furthermore, we have compiled a comprehensive overview of current therapies targeting FGFR1 aberration in cancer, aiming to offer new perspectives for future cancer treatments by focusing on drugs that address specific FGFR1 alterations.

Abstract Background Global warming has greatly increased the impact of high temperatures on crops, resulting in reduced yields and increased mortality. This phenomenon is of significant importance to the rose flower industry because high-temperature stress leads to bud dormancy or even death, reducing ornamental value and incurring economic losses. Understanding the molecular mechanisms underlying the response and resistance of roses to high-temperature stress can serve as an important reference for cultivating high-temperature-stress-resistant roses. Results To evaluate the impact of high temperatures on rose plants, we measured physiological indices in rose leaves following heat stress. Protein and chlorophyll contents were significantly decreased, whereas proline and malondialdehyde (MDA) contents, and peroxidase (POD) activity were increased. Subsequently, transcriptomics and metabolomics analyses identified 4,652 common differentially expressed genes (DEGs) and 57 common differentially abundant metabolites (DAMs) in rose plants from four groups. Enrichment analysis showed that DEGs and DAMs were primarily involved in the mitogen-activated protein kinases (MAPK) signaling pathway, plant hormone signal transduction, alpha-linolenic acid metabolism, phenylpropanoid biosynthesis, and flavonoid biosynthesis. The combined analysis of the DEGs and DAMs revealed that flavonoid biosynthesis pathway-related genes, such as chalcone isomerase (CHI), shikimate O-hydroxycinnamoyl transferase (HCT), flavonol synthase (FLS), and bifunctional dihydroflavonol 4-reductase/flavanone 4-reductase (DFR), were downregulated after heat stress. Moreover, in the MAPK signaling pathway, the expression of genes related to jasmonic acid exhibited a decrease, but ethylene receptor (ETR/ERS), P-type Cu + transporter (RAN1), ethylene-insensitive protein 2/3 (EIN2), ethylene-responsive transcription factor 1 (ERF1), and basic endochitinase B (ChiB), which are associated with the ethylene pathway, were mostly upregulated. Furthermore, heterologous overexpression of the heat stress-responsive gene RcHSP70 increased resistance to heat stress in Arabidopsis thaliana. Conclusion The results of this study indicated that the flavonoid biosynthesis pathway, MAPK signaling pathway, and plant hormones may be involved in high-temperature resistance in roses. Constitutive expression of RcHSP70 may contribute to increasing high-temperature tolerance. This study provides new insights into the genes and metabolites induced in roses in response to high temperature, and the results provide a reference for analyzing the molecular mechanisms underlying resistance to heat stress in roses.

BackgroundCognition disorders not only lead to adverse health consequences but also contribute to a range of socioeconomic challenges and diminished capacity for performing routine daily activities. In the digital era, understanding the impact of digital exclusion on cognitive function is crucial, especially in developing countries. ObjectiveThis study aimed to evaluate the association between digital exclusion and cognitive function among elderly populations in developing countries. MethodsUsing data from CHARLS (China Health and Retirement Longitudinal Study) from 2011 to 2020 and MHAS (Mexican Health & Aging Study) from 2012 to 2021, we defined digital exclusion as self-reported absence from the internet. Cognitive function was assessed through 5 tests: orientation, immediate verbal recall, delayed verbal recall, serial 7s, and figure recall. Cognitive function was assessed in 2 categories: worse cognition (a categorical variable that classifies cognition as either better or worse compared to the entire cohort population) and cognitive scores (a continuous variable representing raw cognitive scores across multiple follow-up waves). Logistic regression analyses and generalized estimating equation (GEE) analyses were used to examine the relationship between cognitive function and digital exclusion, adjusting for potential confounders, including demographics, lifestyle factors, history of chronic diseases, basic activities of daily living (BADL) disability, instrumental activities of daily living (IADL) disability, and basic cognitive abilities. ResultsAfter excluding participants with probable cognitive impairment at baseline and those who did not have a complete cognitive assessment in any given year (ie, all tests in the cognitive assessment must be completed in any follow-up wave), a total of 24,065 participants in CHARLS (n=11,505, 47.81%) and MHAS (n=12,560, 52.19%) were included. Of these, 96.78% (n=11,135) participants in CHARLS and 70.02% (n=8795) in MHAS experienced digital exclusion. Adjusted logistic regression analyses revealed that individuals with digital exclusion were more likely to exhibit worse cognitive performance in both CHARLS (odds ratio [OR] 2.04, 95% CI 1.42-2.99; P.05). The fully adjusted mean differences in global cognitive scores between the 2 groups were 0.98 (95% CI 0.70-1.28; P

Abstract Objective Single nucleotide polymorphisms (SNPs) are common in genes and can lead to dysregulation of gene expression in tissues, which can affect carcinogenesis. Many studies reporting the association between xeroderma pigmentosum group D (XPD) polymorphisms of rs13181 and rs1799793 with oral cancer risk, but with conflicting and inconclusive results. Methods We performed a comprehensive and systematic search through the PubMed, Elsevier, Web of science, and Embase databases, twelve studies were included in the meta-analysis to determine whether XPD rs13181 and rs1799793 polymorphism contributed to the risk of oral cancer. Results The pooled date indicated a significant association between the rs13181 polymorphism and oral cancer risk for the allele comparison model (odds ratio, OR = 1.60, 95% confidence intervals, CI = 1.09–2.35, P = 0.02), the dominant model (OR = 1.74, 95% CI = 1.08–2.82, P = 0.02), and the heterozygote model (OR = 1.59, 95% CI = 1.02–2.49, P = 0.04). For the XPD rs1799793 polymorphism, it is not associated with the incidence of oral cancer under any model. Subgroup analyses based on ethnicity indicated that the rs13181 polymorphism increased the risk of oral cancer among Asians according to the allele comparison model (OR = 1.97, 95% CI = 1.10–3.51, P = 0.02), the dominant model (OR = 2.35, 95% CI = 1.25–4.44, P = 0.008), the heterozygote model (OR = 2.05, 95% CI = 1.15–3.66, P = 0.01), and the homozygous model (OR = 2.47, 95% CI = 1.06–5.76, P = 0.04). Conclusion Our meta-analysis suggests a positive correlation between XPD rs13181polymorphism and the development of oral cancer among Asians, but a negative correlation among Caucasians populations.

Abstract The aim of this study was to investigate and analyse the predictive value of systemic inflammatory markers based on peripheral blood biomarkers for the prognosis of non-small cell lung cancer (NSCLC) patients. Based on a retrospective monitoring cohort of 973 NSCLC patients from an Affiliated Tumor Hospital from 2012 to 2023. The log-rank test and Cox proportional risk regression model were used to identify independent prognostic inflammatory markers. Subsequently, a nomogram prediction model was constructed and evaluated. The results of multivariate Cox regression analysis showed that patients with high NLR group (HR = 1.238, 95% CI 1.015–1.510, P = 0.035), and high CAR group (HR = 1.729, 95% CI 1.408–2.124, P

Abstract In recent years, due to the shortage of blood products, some extensive burn patients were forced to adopt an “ultra-restrictive” transfusion strategy, in which the hemoglobin levels of RBC transfusion thresholds were 0.05). Among the ultra-restrictive transfusion group, patients with RBC transfusion threshold

Laser texturing is a promising technology with wide-ranging applications in surface processing. In this study, a nanosecond laser was used to ablate the surface of Q355 steel, creating grooves of varying depths by different processing times. Satisfactory Al/Steel joints were obtained under different groove depths (0 μm, 6 μm, 26 μm and 56 μm). Interfacial microstructure evolutions were investigated and the observed results indicated that introduction of texture would enhance interfacial specific surface area, promote degree of atomic diffusion, thicken interfacial IMCs (intermetallic metallic compounds) while maintain interfacial reaction (η-Fe2(Al,Si)5 + θ-Fe(Al,Si)3). Numerical simulations results illustrated that existence of texture would reduce interfacial peak residual stress, homogenize residual stress distribution and induce compressive stress in the groove. Highest strength of 111 MPa with the fracture mode of tough-brittle compound fracture was produced in the joint when laser texturing processing times were 20, which was nearly 40 % higher compared to the untreated joint (80 MPa). This study provides a novel method to improve joints mechanical properties for laser welding-brazing of Al/Steel system, which may also provide a theoretical reference for the application of other dissimilar metal systems.

Abstract Cancer cells consistently utilize the unfolded protein response (UPR) to encounter the abnormal endoplasmic reticulum (ER) stress induced by the accumulation of misfolded proteins. Extreme activation of the UPR could also provoke maladaptive cell death. Previous reports have shown that NRF2 antioxidant signaling is activated by UPR and serves as noncanonical pathway to defense and reduce excessive ROS levels during ER stress. However, the mechanisms of regulating NRF2 signaling upon ER stress in glioblastoma have not been fully elucidated. Here we identify that SMURF1 protects against ER stress and facilitates glioblastoma cell survival by rewiring KEAP1-NRF2 pathway. We show that ER stress induces SMURF1 degradation. Knockdown of SMURF1 upregulates IRE1 and PERK signaling in the UPR pathway and prevents ER-associated protein degradation (ERAD) activity, leading to cell apoptosis. Importantly, SMURF1 overexpression activates NRF2 signaling to reduce ROS levels and alleviate UPR-mediated cell death. Mechanistically, SMURF1 interacts with and ubiquitinates KEAP1 for its degradation (NRF2 negative regulator), resulting in NRF2 nuclear import. Moreover, SMURF1 loss reduces glioblastoma cell proliferation and growth in subcutaneously implanted nude mice xenografts. Taken together, SMURF1 rewires KEAP1-NRF2 pathway to confer resistance to ER stress inducers and protect glioblastoma cell survival. ER stress and SMURF1 modulation may provide promising therapeutic targets for the treatment of glioblastoma.

Abstract Background Macro-autophagy/Autophagy is an evolutionarily well-conserved recycling process to maintain the balance through precise spatiotemporal regulation. However, the regulatory mechanisms of biomolecular condensates by the key adaptor protein p62 via liquid-liquid phase separation (LLPS) remain obscure. Results In this study, we showed that E3 ligase Smurf1 enhanced Nrf2 activation and promoted autophagy by increasing p62 phase separation capability. Specifically, the Smurf1/p62 interaction improved the formation and material exchange of liquid droplets compared with p62 single puncta. Additionally, Smurf1 promoted the competitive binding of p62 with Keap1 to increase Nrf2 nuclear translocation in p62 Ser349 phosphorylation-dependent manner. Mechanistically, overexpressed Smurf1 increased the activation of mTORC1 (mechanistic target of rapamycin complex 1), in turn leading to p62 Ser349 phosphorylation. Nrf2 activation increased the mRNA levels of Smurf1, p62, and NBR1, further promoting the droplet liquidity to enhance oxidative stress response. Importantly, we showed that Smurf1 maintained cellular homeostasis by promoting cargo degradation through the p62/LC3 autophagic pathway. Conclusions These findings revealed the complex interconnected role among Smurf1, p62/Nrf2/NBR1, and p62/LC3 axis in determining Nrf2 activation and subsequent clearance of condensates through LLPS mechanism.

In this study, we advance our exploration of Apolipoprotein A-I (apoA-I) peptide analogs (APAs) for their application in nanodisc (ND) assembly, focusing on the dynamic conformational characteristics and the potential for drug delivery. We explore APA-ND interactions with an emphasis on curcumin encapsulation, utilizing molecular dynamic simulations and in vitro assessments to evaluate the efficacy of various APA-ND formulations as drug carriers. The methodological approach involved the generation of three unique apoA-I α-11/3 helical mimics, resulting in fifteen distinct APAs. Their structural integrity was rigorously assessed using ColabFold-AF2, with particular attention to pLDDT and pTM scores. Extensive molecular dynamics simulations, covering 1.7 μs across 17 ND systems, were conducted to investigate the influence of APA sequence variations on ND stability and interactions. This study reveals that the composition of APAs, notably the presence of Proline, Serine, and Tryptophan, significantly impacts ND stability and morphology. Oligomeric APAs, in particular, demonstrated superior stability and distinct interaction patterns compared to their monomeric counterparts. Additionally, hydrodynamic diameter measurements over eight weeks indicated sequence-dependent stability, highlighting the potential of specific APA configurations for sustained colloidal stability. In vitro study successfully encapsulated curcumin in [AA]3/DMPC ND formulations, revealing concentration-dependent stability and interaction dynamics. The findings underscore the remarkable capability of APA-NDs to maintain structural integrity and efficient drug encapsulation, positioning them as a promising platform for drug delivery. The study concludes by emphasizing the tunability and versatility of APA-NDs in drug formulation, potentially revolutionizing nanomedicine by enabling customized APA sequences and ND properties for targeted drug delivery.

Biomimetic delivery systems (BDSs), inspired by the intricate designs of biological systems, have emerged as a groundbreaking paradigm in nanomedicine, offering unparalleled advantages in therapeutic delivery. These systems, encompassing platforms such as liposomes, protein-based nanoparticles, extracellular vesicles, and polysaccharides, are lauded for their targeted delivery, minimized side effects, and enhanced therapeutic outcomes. However, the translation of BDSs from research settings to clinical applications is fraught with challenges, including reproducibility concerns, physiological stability, and rigorous efficacy and safety evaluations. Furthermore, the innovative nature of BDSs demands the reevaluation and evolution of existing regulatory and ethical frameworks. This review provides an overview of BDSs and delves into the multifaceted translational challenges and present emerging solutions, underscored by real-world case studies. Emphasizing the potential of BDSs to redefine healthcare, we advocate for sustained interdisciplinary collaboration and research. As our understanding of biological systems deepens, the future of BDSs in clinical translation appears promising, with a focus on personalized medicine and refined patient-specific delivery systems.

This paper demonstrates a C-band 25G colorless passive optical network (PON) based on semiconductor optical amplifier (SOA) and 10G electro-absorption modulator (EAM). The experimental results show that the SOA in the optical network unit (ONU) can erase the downlink signal by taking advantage of the gain saturation feature, realizing the reuse of downstream wavelength. Meanwhile, the SOA gain can compensate for the EAM loss by optimizing the current and injection power. Apart from this, equalization algorithms at the optical line terminal are investigated for linear and nonlinear impairments compensation. Besides, the system robustness to the ASE and the maximum transmission speed are also evaluated. Finally, the system capacity can reach up to 25 Gbps with NRZ format at a bit-error ratio threshold of 2 × 10−2, proving that this system is a promising technology for future high-speed colorless 2 × 25G or 4 × 25G Wavelength division Multiplexing (WDM) PON system.

Ghost imaging (GI) retrieves an image from the correlation between a sequence of illumination patterns on the object and their corresponding bucket detections. Traditionally, GI requires the precise information of the illumination patterns, which raises technology barriers on building a high-speed illumination source, limiting the scope of its application. In this study, we propose a high-speed GI system, which implements a self-correlation with a purely optical operation without determining illumination patterns. The light source is an optical phased array (OPA), built of a set of waveguide-type electro-optic phase modulators. The OPA is driven to randomly change the phases in every 200 ns, generating speckle patterns at a rate of 5 MHz. Although the speckle patterns are not predictable or post-determinable, with the help of the naked-eye GI scheme, the system in real time optically generates the images of the object at a frame rate of more than 1 kHz, which can be directly observed by eyes or using a camera. This method avoids acquiring the information of the illumination, thus providing a simple and easy way to realize high-speed GI. It also inspires a different way of applying OPAs to high-speed imaging.

Molecular dynamic behaviors of nanodisc (ND) formulations of free doxorubicin (DOX) and DOX conjugated lipid prodrug molecules were investigated by molecular dynamics (MD) simulations. We have unveiled how formulation design affects the drug release profile and conformational stability of ND assemblies. Our simulation results indicate that free DOX molecules loaded in the ND system experienced rapid dissociation due to the unfavorable orientation of DOX attached to the lipid surface. It is found that DOX tends to form aggregates with higher drug quantities. In contrast, lipidated DOX-prodrugs incorporated in ND formulations exhibited sufficient ND conformational stability. The drug loading capacity is dependent on the type of lipid molecules grafted on the DOX-prodrug, and the drug loading quantities in a fixed area of NDs follow the order: DOX-BMPH-MP > DOX-BMPH-TC > DOX-BMPH-PTE. To gain further insight into the dynamic characteristics of ND formulations governed by different kinds of lipidation, we investigated the conformational variation of ND components, intermolecular interactions, the solvent accessible surface area, and individual MSP1 residue flexibility. We found that the global conformational stability of DOX-prodrug-loaded ND assemblies is influenced by the molecular flexibility and lipidated forms of DOX-prodrug. We also found that the spontaneous self-aggregation of DOX-prodrugs with increasing quantities on ND could reduce the membrane fluidity and enhance the conformational stability of ND formulations.

Background: The sharing and utilization of online users' information has become an important resource for governments to manage COVID-19; however, it also involves the risk of leakage of users' personal information. Online users' sharing decisions regarding personal information and the government's COVID-19 prevention and control decisions influence each other and jointly determine the efficiency of COVID-19 control and prevention.Method: Using the evolutionary game models, this paper examines the behavioral patterns of online users and governments with regard to the sharing and disclosure of COVID-19 information for its prevention and control.Results: This paper deduce the reasons and solutions underlying the contradiction between the privacy risks faced by online users in sharing information and COVID-19 prevention and control efforts. The inconsistency between individual and collective rationality is the root cause of the inefficiency of COVID-19 prevention and control.Conclusions: The reconciliation of privacy protection with COVID-19 prevention and control efficiency can be achieved by providing guidance and incentives to modulate internet users' behavioral expectations.

Abstract Background In this case report, giant calculus in the urethral diverticulum was found through ureteroscopy investigation, the pneumatic lithotripsy combined with ultrasound lithotripsy (PLCUL) was successfully performed to break down this rare and giant urethral calculus in the diverticulum without open surgery. Case presentation A 82-year-old male presented to the urology department, complaining of frequent urination and dysuria. One giant, dark brown stone (6.5 × 6 × 5.5 cm) was revealed in the diverticulum of the anterior urethra using combination of local ultrasound, pelvic Computer Tomography (CT) and Magnetic Resonance Imaging (MRI). The stone was then successfully broken down via the PLCUL, and the emptied anterior urethral diverticulum was left untreated. In the 18 months’ follow-up, no new calculus was found in urethral tract, anterior diverticula became gradually smaller, eventually disappeared. Conclusion In the treatment of giant calculus in the urethral diverticulum, this case report provides an effective method of lithotripsy in the clinical trials.

Melittin is a membrane-active peptide with strong anticancer activity against various cancers. Despite decades of research, the role of the singular Trp in the anticancer activity and selectivity of melittin remains poorly understood. Here, we propose a theranostic solution based on the substitution of Trp19 with a noncanonical fluorescent amino acid (DapAMCA). The introduction of DapAMCA residue in melittin stabilized the helical structure of the peptide, as evaluated by circular dichroism spectra and molecular dynamics simulations. In vitro hemolytic and anticancer activity assays revealed that introducing DapAMCA residue in melittin changed its mode of action with the cell membrane, resulting in reduced hemolytic toxicity and an improved the selectivity index (SI), with up to a five-fold increase compared to melittin. In vitro fluorescence imaging of DapAMCA-labeled melittin (MELFL) in cancer cells demonstrated high membrane-penetrating activity, with strong nuclear and nucleolar localization ability. These findings provide implications for novel anticancer therapies based on Trp-substituted designs and nuclear/nucleolar targeted therapy.

Pseudomonas aeruginosa (PA) is a major cause of nosocomial infections, which remain an unsolved problem in the clinic despite conventional antibiotic treatment. A PA vaccine could be both an effective and economical strategy to address this issue. Many studies have shown that PcrV, a structural protein of the type 3 secretion system (T3SS) from PA, is an ideal target for immune prevention and therapy. However, difficulties in the production of high-quality PcrV likely hinder its further application in the vaccine industry. Thus, we hypothesized that an optimized PcrV derivative with a rational design could be produced. In this study, the full-length PcrV was divided into four domains with the guidance of its structure, and the Nter domain (Met1-Lys127) and H12 domain (Leu251-Ile294) were found to be immunodominant. Subsequently, Nter and H12 were combined with a flexible linker to generate an artificial PcrV derivative (PcrVNH). PcrVNH was successfully produced in E. coli and behaved as a homogenous monomer. Moreover, immunization with PcrVNH elicited a multifactorial immune response and conferred broad protection in an acute PA pneumonia model and was equally effective to full-length PcrV. In addition, passive immunization with anti-PcrVNH antibodies alone also showed significant protection, at least based on inhibition of the T3SS and mediation of opsonophagocytic killing activities. These results provide an additional example for the rational design of antigens and suggest that PcrVNH is a promising vaccine candidate for the control of PA infection.

Asthma is a chronic inflammatory disorder, previous studies have shown that IL-17A contributes to the development of asthma, and there is a positive correlation between the level of IL-17A and the severity of disease. Here, we constructed recombinant Mycobacterium smegmatis expressing fusion protein Ag85A-IL-17A (rMS-Ag85a-IL-17a) and evaluated whether it could attenuate allergic airway inflammation, and further investigated the underlying mechanism. In this work, the murine model of asthma was established with ovalbumin, and mice were intranasally vaccinated with rMS-Ag85a-IL-17a. Autoantibody of IL-17A in sera was detected, and the airway inflammatory cells infiltration, the local cytokines and chemokines production and the histopathological changes of lung tissue were investigated. We found that the administration of rMS-Ag85a-IL-17a induced the autoantibody of IL-17A in sera. The vaccination of rMS-Ag85a-IL-17a remarkably reduced the infiltration of inflammatory cells and the secretion of mucus in lung tissue and significantly decreased the numbers of the total cells, eosinophils and neutrophils in BALF. Th1 cells count in spleen, Th1 cytokine levels in BALF and supernatant of splenocytes and mediastinal lymph nodes, and T-bet mRNA in lung tissue were significantly increased with rMS-Ag85a-IL-17a administration. Meanwhile, rMS-Ag85a-IL-17a vaccination markedly decreased Th2 cells count, Th2 cytokine and Th17 cytokine levels in BALF and supernatant of splenocytes and mediastinal lymph nodes, and chemokines mRNA expression in lung tissue. These data confirmed that recombinant Mycobacterium smegmatis in vivo could induce autoantibody of IL-17A, which attenuated asthmatic airway inflammation.

Abstract To effectively treat osteoarthritis (OA), the existing inflammation must be reduced before the cartilage damage can be repaired; this cannot be achieved with a single type of extracellular vesicles (EVs). Here, a hydrogel complex with logic‐gates function is proposed that can spatiotemporally controlled release two types of EVs: interleukin 10 (IL‐10)+ EVs to promote M2 polarization of macrophage, and SRY‐box transcription factor 9 (SOX9)+ EVs to increase cartilage matrix synthesis. Following dose‐of‐action screening, the dual EVs are loaded into a matrix metalloporoteinase 13 (MMP13)‐sensitive self‐assembled peptide hydrogel (KM13E) and polyethylene glycol diacrylate/gelatin methacryloyl‐hydrogel microspheres (PGE), respectively. These materials are mixed to form a “microspheres‐in‐gel” KM13E@PGE system. In vitro, KM13E@PGE abruptly released IL‐10+ EVs after 3 days and slowly released SOX9+ EVs for more than 30 days. In vivo, KM13E@PGE increased the CD206+ M2 macrophage proportion in the synovial tissue and decreased the tumor necrosis factor‐α and IL‐1β levels. The aggrecan and SOX9 expressions in the cartilage tissues are significantly elevated following inflammation subsidence. This performance is not achieved using anti‐inflammatory or cartilage repair therapy alone. The present study provides an injectable, integrated delivery system with spatiotemporal control release of dual EVs, and may inspire logic‐gates strategies for OA treatment.

Abstract Non-small cell lung cancer (NSCLC) is the malignant tumor with the highest morbidity and leading cause of death worldwide, whereas its pathogenesis has not been fully elucidated. Although mutations in some crucial genes in WNT pathways such as β-catenin and APC are not common in NSCLC, the abnormal signal transduction of WNT pathways is still closely related to the occurrence and progression of NSCLC. WNT ligands (WNTs) are a class of secreted glycoproteins that activate WNT pathways through binding to their receptors and play important regulatory roles in embryonic development, cell differentiation, and tissue regeneration. Therefore, the abnormal expression or dysfunction of WNTs undoubtedly affects WNT pathways and thus participates in the pathogenesis of diseases. There are 19 members of human WNTs, WNT1, WNT2, WNT2b, WNT3, WNT3a, WNT4, WNT5a, WNT5b, WNT6, WNT7a, WNT7b, WNT8a, WNT8b, WNT9a, WNT9b, WNT10a, WNT10b, WNT11 and WNT16. The expression levels of WNTs, binding receptors, and activated WNT pathways are diverse in different tissue types, which endows the complexity of WNT pathways and multifarious biological effects. Although abundant studies have reported the role of WNTs in the pathogenesis of NSCLC, it still needs further study as therapeutic targets for lung cancer. This review will systematically summarize current research on human WNTs in NSCLC, from molecular pathogenesis to potential clinical practice.

[Objectives] The aim was to elucidate the pro-apoptosis mechanism of naphthoquinone derivative 2-octyl sulfoxide-1, 4-naphthoquinone(OSNQ) on human colon cancer SW480 cells. [Methods]The cytotoxic effect of OSNQ on colon cancer SW480 cells was detected by MTT colorimetry. The pro-apoptotic effect of OSNQ on human colon cancer SW480 cells was detected by Annexin V-FITC/PI double staining. The changes in expression of apoptosis-related proteins were detected by Western blot. [Results]The results of MTT assay showed that OSNQ had a significant cytotoxic effect on colon cancer SW480 cells. The results of Western blot showed that OSNQ induced the apoptosis in colon cancer SW480 cells through promoting the expression of pro-apoptotic caspase-3 and inhibiting the expression of apoptosis-inhibiting protein Bcl-2. [Conclusions] OSNQ has a significant cytotoxic effect on colon cancer SW480 cells, and it induces the apoptosis of colon cancer SW480 cells by AKT signaling pathway. [ABSTRACT FROM AUTHOR]

[Objectives] The aim was to investigate the effect of cryptotanshinone on apoptosis of human melanoma A375 cells and its related mechanism of mitochondrial pathway. [Methods]The cytotoxic effect of cryptotanshinone on apoptosis of human melanoma A375 cells was detected by MTT colorimetry. The apoptosis of melanoma A375 cells was detected with Annexin V-FITC/PI and observed by fluorescence inverted microscope. The expression of apoptosis-related proteins was detected by Western blotting. [Results]The viability of the A375 cells decreased with the increase of drug concentration. The fluorescence intensity of the cells increased with the treatment time. The expression of pro-apoptotic protein caspase-3 gradually increased, while the expression of apoptosis-inhibiting proteins p-AKT and Bcl-2 gradually reduced. [Conclusions]Cryptotanshinone induces apoptosis of human melanoma A375 cells via AKT signaling pathway, thus exerting a good cytotoxic effect on A375 cells. [ABSTRACT FROM AUTHOR]

Cryptotanshinone is a natural active ingredient extracted from traditional Chinese medicine Radix Salviae Miltiorrhizae. It has a variety of pharmacological effects, in addition to preventing and treating ischemic diseases, coronary artery disease Alzheimer's disease and fighting tumors.The anti-tumor effects are exerted through inhibiting tumor cell proliferation, inducing tumor cell apoptosis, inhibiting tumor metastasis and invasion, inhibiting angiogenesis and regulating reactive oxygen species levels. The studies on the anti-tumor activity and action mechanism of cryptotanshinone in recent years are reviewed in this article. [ABSTRACT FROM AUTHOR]

In this work, we investigate a temporal decomposition approach to long-horizon dynamic optimization problems. The problems are discrete-time, linear, time dependent, and with box constraints on the control variables. We prove that an overlapping domains temporal decomposition, while inexact, approaches the solution of the long-horizon dynamic optimization problem exponentially fast in the size of the overlap. The resulting subproblems share no solution information and thus can be computed independently in parallel. Our findings are demonstrated with a small, synthetic production cost model with real demand data. [ABSTRACT FROM AUTHOR]

[Objectives] This study was conducted to elucidate the mechanism of action of total glucosides of paeony (TGP) against the liver injury induced by isoniazid (INH) and rifampicin (RFP), and to provide experimental evidence for rational use of anti-tuberculosis drugs. [Methods] Liver injury in mice was induced by the combination of INH and RFP in mice. After the mice were given different doses of Total Glucosides of White Paeony Capsules (TGP) for 10 d, the hepatosomatic index, biochemical indices in serum and liver homogenate were measured, and histopathological changes in liver tissue were observed. Glucurolactone was used as the positive control, and 0.9% sodium chloride was used as the negative control in the experiment. [Results] TGP reduced the activities of alanine transaminase (ALT) and aspartate transferase (AST) in serum and the level of malondialdehyde (MDA) in liver tissue, and increased the level of glutathione (GSH) and the activity of superoxidase dismutase (SOD) in liver tissue. [Conclusions] TAP has a protective effect against the liver injury induced by INH and RFP. [ABSTRACT FROM AUTHOR]

[Objectives] To investigate the pharmacologic effects of active components from A. membranaceus on human esophageal cancer HCE-4 cells and its apoptosis mechanism. [Methods] The viabilities of HCE-4 cells were measured by MTT asay. The induction of active components from A. membranaceus on apoptosis of HCE-4 cells was detected by Annexin V-FITC/PI double staining. The apoptotic-related protein expression levels were determined by Western blotting. [Results] Formononetin and astragaloside IV suppressed the proliferation of HCE-4 cells in a dose-dependent manner. The Annexin V-FITC/PI double staining results showed that formononetin and astragaloside IV could induce HCE-4 cells apoptosis in a time-dependent manner. The Western blotting results showed that formononetin and atragaloside IV could significantly down-regulate p-iVKT, pro-caspae-3, ad increase cle-caspase-3 protein expression in HCE-4 cells. [Conclusions] Active components from A. membranaceus such as formononetin ad astragaloside IV significantly inhibited the proliferation of human esophageal cancer HCE-4 cells by inducing mitochondrial dependent apoptosis via AKT signaling pathway. [ABSTRACT FROM AUTHOR]

Glycyrrhiza uralensis Fisch has been used to treat the symptoms of organ fever, food poisoning, typhoid fever, sore throat, cough due to lung heat, children’s diseases and so on since the ancient times. It is a solid Chinese herbal medicine which is good for the health. In recent years, it has been found that licorice extract also has excellent anti-cancer effect. The 18β glycyrrhetinic acid, obtained by hydrolysis of precursor glycyrrhizic acid, is a relatively efficient anti-cancer ingredient. 18β glycyrrhetinic acid can exert anti-cancer effects by inhibiting cancer cell proliferation, inducing apoptosis of cancer cells, inhibiting invasion and metastasis of cancer cells, preventing oxidation, inhibiting neovascularization, inhibiting lymphangiogenesis, and regulating hormone secretion. This paper reviewed the advances in research of the anticancer mechanism of 18β glycyrrhetinic acid, to provide a theoretical basis for future research. [ABSTRACT FROM AUTHOR]

Maximum-likelihood-based state estimation for dynamical systems with model error raises computational challenges in memory usage due to the much larger number of free variables when compared to the perfect model case. To address this challenge, we present a limited-memory method for maximum-likelihood-based estimation of state space models. We reduce the memory storage requirements by expressing the optimal states as a function of checkpoints bounding a shooting interval. All states can then be recomputed as needed from a recursion stemming from the optimality conditions. The matching of states at checkpoints is imposed, in a multiple shooting fashion, as constraints on the optimization problem, which is solved with an augmented Lagrangian method. We prove that for nonlinear systems under certain assumptions the condition number of the Hessian matrix of the augmented Lagrangian function is bounded above with respect to the number of shooting intervals. Hence the method is stable for increasing time horizon. The assumptions include satisfying the observability conditions of the linearized system on a shooting interval. We also propose a recursion-based gradient evaluation algorithm for computing the gradient, which in turn allows the algorithm to proceed by storing at any time only the checkpoints and the states on a shooting interval. We demonstrate our findings with simulations in different regimes for Burgers' equation. [ABSTRACT FROM AUTHOR]

Isoliquiritigenin could play an antitumor role by inhibiting proliferation of tumor cells, inducing apoptosis of tumor cells and resisting neovascularity. In this paper, antitumor activity and mechanism of isoliquiritigenin are summarized. [ABSTRACT FROM AUTHOR]

Normal aging in humans and rodents is accompanied by a progressive increase in adiposity. To investigate the role of hypothalamic neuronal circuits in this process, we used a Cre-lox strategy to create mice with specific and progressive degeneration of hypothalamic neurons that express agouti-related protein (Agrp) or proopiomelanocortin (Pomc), neuropeptides that promote positive or negative energy balance, respectively, through their opposing effects on melanocortin receptor signaling. In previous studies, Pomc mutant mice became obese, but Agrp mutant mice were surprisingly normal, suggesting potential compensation by neuronal circuits or genetic redundancy. Here we find that Pomc-ablation mice develop obesity similar to that described for Pomc knockout mice, but also exhibit defects in compensatory hyperphagia similar to what occurs during normal aging. Agrp-ablation female mice exhibit reduced adiposity with normal compensatory hyperphagia, while animals ablated for both Pomc and Agrp neurons exhibit an additive interaction phenotype. These findings provide new insight into the roles of hypothalamic neurons in energy balance regulation, and provide a model for understanding defects in human energy balance associated with neurodegeneration and aging.