Development of D-π-A organic dyes for discriminating HSA from BSA and study on dye-HSA interaction.

HSA (human serum albumin), a most abundant protein in blood serum, plays a key role in maintaining human health. Abnormal HSA level is correlated with many diseases, and thus has been used as an essential biomarker for therapeutic monitoring and biomedical diagnosis. Development of small-molecule fluorescent probes allowing the selective and sensitive recognition of HSA in in vitro and in vivo is of fundamental importance in basic biological research as well as medical diagnosis. Herein, we reported a series of new synthesized fluorescent dyes containing D-π-A constitution, which exhibited different optical properties in solution and solid state. Among them, dye M-H-SO3 with a hydrophilic sulfonate group at electron-acceptor part displayed selectivity for discrimination of HSA from BSA and other enzymes. Upon binding of dye M-H-SO3 with HSA, a significant fluorescence enhancement with a turn-on ratio about 96-fold was triggered. The detection limit was estimated to be âˆ¼ 40 nM. Studies on the interaction mechanism revealed that dye M-H-SO3 could bind to site III of HSA with a 1:1 binding stoichiometry. Furthermore, dye M-H-SO3 has been applied to determine HSA in real urine samples with good recoveries, which provided a useful method for HSA analysis in biological fluids.

GSH-activable heterotrimeric nano-prodrug for precise synergistic therapy of TNBC.

Combination chemotherapy is an effective approach for triple-negative breast cancer (TNBC) therapy, especially when drugs are administered at specific optimal ratios. However, at present, strategies involving precise and controllable ratios based on effective loading and release of drugs are unavailable. Herein, we designed and synthesized a glutathione (GSH)--responsive heterotrimeric prodrug and formulated it with an amphiphilic polymer to obtain nanoparticles (DSSC2 NPs) for precise synergistic chemotherapy of TNBC. The heterotrimeric prodrug was prepared using docetaxel (DTX) and curcumin (CUR) at the optimal synergistic ratio of 1: 2. DTX and CUR were covalently conjugated by disulfide linkers. Compared with control NPs, DSSC2 NPs had quantitative/ratiometric drug loading, high drug co-loading capacity, better colloidal stability, and less premature drug leakage. After systemic administration, DSSC2 NPs selectively accumulated in tumor tissues and released the encapsulated drugs triggered by high levels of GSH in cancer cells. In vitro and in vivo experiments validated that DSSC2 NPs released DTX and CUR at the predefined ratio and had a highly synergistic therapeutic effect on tumor suppression in TNBC, which can be attributed to ratiometric drug delivery and synchronous drug activation. Altogether, the heterotrimeric prodrug delivery system developed in this study represents an effective and novel approach for combination chemotherapy.

Synergistic acceleration of machine learning and molecular docking for prostate-specific antigen ligand design.

Prostate-specific antigen (PSA) serves as a critical biomarker for the early detection and continuous monitoring of prostate cancer. However, commercial PSA detection methods primarily rely on antigen-antibody interactions, leading to issues such as high costs, stringent storage requirements, and potential cross-reactivity due to PSA variant sequence homology. This study is dedicated to the precise design and synthesis of molecular entities tailored for binding with PSA. By employing a million-level virtual screening to obtain potential PSA compounds and effectively guiding the synthesis using machine learning methods, the resulting lead compounds exhibit significantly improved binding affinity compared to those developed before by researchers using high-throughput screening for PSA, substantially reducing screening and development costs. Unlike antibody detection, the design of these small molecules offers promising avenues for advancing prostate cancer diagnostics. Furthermore, this study establishes a systematic framework for the rapid development of customized ligands that precisely target specific protein entities.

[Development and Clinical Application of Multifunctional Inflation-Free Lumpectomy Aid].

To investigate the value of self-developed air-free laparoscopic auxiliary instruments in the clinical application of thyroid diseases. The clinical data of 70 transaxillary and 45 transareolar air-free laparoscopic surgeries for thyroid cancer and 40 conventional open surgeries were retrospectively compared. The transaxillary and transareolar laparoscopic groups had significantly longer operative times than the open group, while the postoperative satisfaction was higher in the endoscopic group than in the open group. This set of instruments has advantage of novel design, scientific structure, safe application. It can be compatible with a variety of thyroid and breast air-free laparoscopic procedures, which can promote the development and popularization of laparoscopic technology.

Clinical analysis of a new multifunctional instrument set for gasless endoscopic thyroidectomy with two different approaches.

BACKGROUND: Following the rapid development of endoscopic thyroidectomy techniques, various surgical procedures have been developed (e.g., transoral, submandibular, areolar, axillary, retroauricular, and combined procedures), and each of these procedures has its own advantages. In recent years, gasless endoscopic thyroidectomy has emerged as a feasible procedure, and it has replaced traditional CO2 insufflation approaches because of advantages such as stable cavity construction, pollution reduction, resource saving, and risk reduction. However, each gasless procedure requires special instruments for cavity construction, and this results in enormous wastage of medical resources. In the present study, we introduced a set of instruments developed by our team. This set of instruments is designed to be compatible with the current gasless endoscopic thyroidectomy approaches, including transoral, submandibular, transareolar, transaxillary, retroauricular, combined, and lateral cervical lymph node dissection. Here, we introduced this set of instruments for two gasless endoscopic thyroidectomy procedures (transaxillary and transareolar). Following the incorporation of this set of instruments in regular clinical practice, it could be used for more gasless endoscopic thyroidectomy procedures in the future. OBJECTIVE: To investigate the feasibility, safety, and efficacy of the self-developed instruments for gasless endoscopic thyroidectomy in two different approaches. METHODS: A total of 180 patients diagnosed to have papillary thyroid carcinoma (PTC) between January 2020 and April 2022 were retrospectively investigated. The patients were assigned to a gasless transaxillary group (group A) and a gasless transareolar group (group B). The same gasless endoscopic-assisted instruments were used for both groups. The clinical characteristics, treatment results, and complications were compared between the two groups. RESULTS: All 180 patients were successfully operated. The extent of surgical resection in all patients was the same: "unilateral glandular lobectomy + isthmus combined with ipsilateral central zone lymph node dissection." There were 130 and 50 patients in group A and group B, respectively; one patient in the former group was converted to open surgery due to intraoperative bleeding. No significant difference was observed between the two groups in terms of gender, age, body mass index (BMI), education level, and proportion of concomitant Hashimoto's thyroiditis (P > 0.05). The establishment of cavity time was significantly longer in group A than in group B (35.62 ± 5.07 min vs. 17.46 ± 2.55 min, P < 0.01). The number of lymph nodes cleared was slightly less in group A than in group B (4.06 ± 2.93 vs. 4.52 ± 2.38, P = 0.07). Moreover, the two groups showed no significant differences (P > 0.05) in the total operative time (145.54 ± 45.11 min vs. 143.06 ± 46.70 min), tumor size (0.68 ± 0.46 cm vs. 0.71 ± 0.49 cm), postoperative hospital stay (4.08 ± 1.48 days vs. 3.72 ± 1.07 days), vocal cord paralysis [4 (3.1%) vs. 2 (4%)], postoperative swallowing discomfort [24 (18.5%) vs. 5 (10%)], and postoperative recurrence and satisfaction scores (3.27 ± 1.52 vs. 3.28 ± 1.53). CONCLUSION: Although the two approaches of gasless endoscopic surgery have different operative paths and different time periods for cavity construction, both approaches are similar in terms of the principle of cavity construction, safe and reliable postoperative efficacy, and good cosmetic effect. Therefore, the same set of instruments can be used to complete the surgery in both approaches, thus saving medical resources and facilitating the popularization of this technology.

LncRNA MIR31HG promotes cell proliferation and invasive properties of the MCF-7 cell line by regulation of receptor-interacting serine-threonine kinase 4.

LncRNA MIR31HG is involved in many types of cancers, while its roles in breast cancer are still unknown. The current study aimed to explore the function of lncRNA MIR31HG in breast cancer and the underlying mechanisms. Stable expression cell lines were constructed by using lentivirus particles. MTT assay was used to determine cell viability. Wound healing and Transwell assay were used to determine cell migration and invasion, respectively. The changes in biomarkers were determined by using qPR-PCT and Western blotting, respectively. BALB/c nude mice were used to generate a xenograft mouse model. MIR31HG regulated cell proliferation, migration and invasion in MCF7 cells. Besides, MIR31HG regulated N-Cadherin, Vimentin, and E-Cadherin. MIR31HG positively regulated receptor-interacting serine-threonine kinase 4 (RIPK4), as supported by the fact that knockdown of MIR31HG suppressed RIPK4, and the knockdown of RIPK4 did not affect MIR31HG. Additionally, we found that RIPK4 regulated cell proliferation, migration and invasion in MCF7 cells. The changes in RIPK4 regulated N-Cadherin, Vimentin, and E-Cadherin. Consistently, in vivo studies showed that the knockdown of MIR31HG or RIPK4 reduced tumor size in xenograft animal models. The roles of lncRNA MIR31HG in breast cancer were associated with its regulatory effects against RIPK4.

Lack of association between XRCC1 SNPs and acute radiation­induced injury or prognosis in patients with nasopharyngeal carcinoma.

The response to radiation therapy (RT) is closely associated with DNA damage repair. X-ray repair cross-complementing group-1 (XRCC1) is a key gene in the DNA damage repair pathway, and SNPs in this gene alter the expression and activity of its effector protein, which may in turn affect sensitivity to RT. Therefore, the course of tumor treatment and local control rate can be influenced. In the present study, a group of 158 patients with nasopharyngeal carcinoma (NPC) who received intensity-modulated RT at Fujian Cancer Hospital (Fuzhou, China) between July 2012 and October 2013 were included in retrospective chart review and followed up. Plasma was collected before treatment for genotype analysis of the three SNPs of XRCC1, namely Arg194Trp, Arg280His and Arg399Gln. Acute radiation-induced injuries sustained during treatment was graded according to the Radiation Therapy Oncology Group scoring criteria. Post-treatment follow-up was performed until August 2020. In the 158 cases of NPC, no statistically significant association was observed between the three SNPs of the XRCC1 gene and the severity of acute radiation-induced injury or prognosis. However, the AA genotype of XRCC1-Arg399Gln tended to be associated with worse progression-free survival (PFS) compared with the GA + GG genotype, although this was not significant (P=0.069). In addition, multivariate logistic analysis showed that nodal stage was significantly associated with the occurrence of acute severe radiation-induced oral mucositis (P=0.018), and there was also a trend towards an association between nodal stage and the incidence of acute severe radiation-induced pharyngitis; however, this was not statistically significant (P=0.061). Furthermore, multivariate Cox regression analysis showed that older age, distant metastasis and higher clinical stage were independent risk factors for PFS in patients with NPC. In conclusion, relying solely on the aforementioned SNPs of the XRCC1 gene may not provide a robust enough basis to predict the response to RT or prognosis in patients with NPC.

Secoisolariciresinol diglucoside regulates estrogen receptor expression to ameliorate OVX-induced osteoporosis.

OBJECTIVE: Secoisolariciresinol diglucoside (SDG) is a phytoestrogen that has been reported to improve postmenopausal osteoporosis (PMOP) caused by estrogen deficiency. In our work, we aimed to investigate the mechanism of SDG in regulating the expressions of ERs on PMOP model rats. METHODS: Ovariectomization (OVX) was used to establish PMOP model in rats. The experiment was allocated to Sham, OVX, SDG and raloxifene (RLX) groups. After 12-week treatment, micro-CT was used to detect the transverse section of bone. Hematoxylin and Eosin staining and Safranine O-Fast Green staining were supplied to detect the femur pathological morphology of rats. Estradiol (E2), interleukin-6 (IL-6), bone formation and bone catabolism indexes in serum were detected using ELISA. Alkaline phosphatase (ALP) staining was used to detect the osteogenic ability of chondrocytes. Immunohistochemistry and Western blot were applied to detect the protein expressions of estrogen receptors (ERs) in the femur of rats. RESULTS: Compared with the OVX group, micro-CT results showed SDG could lessen the injury of bone and improve femoral parameters, including bone mineral content (BMC) and bone mineral density (BMD). Pathological results showed SDG could reduce pathological injury of femur in OVX rats. Meanwhile, SDG decreased the level of IL-6 and regulated bone formation and bone catabolism indexes. Besides, SDG increased the level of E2 and conversed OVX-induced decreased the expression of ERα and ERß. CONCLUSION: The treatment elicited by SDG in OVX rats was due to the reduction of injury and inflammation and improvement of bone formation index, via regulating the expression of E2 and ERs.

A safety study on ultra­high or moderate static magnetic fields combined with platycodin D against lung cancer.

Due to the serious side effects of chemotherapy drugs against lung cancer, and the antitumor properties and high safety of magnetic fields, the present study combined moderate or ultra-high intensity statics magnetic fields (SMFs) with platycodin D (PD) to explore the antitumor efficiency and biosafety. The antitumor effects of PD with or without moderate and ultra-high SMFs on A549 cells bearing mice were compared. Mouse body weight, food/water intake, hematology routine, blood biochemistry, tumor weight and tissues hematoxylin and eosin (H&E) staining were examined. Behavior was measured using the elevated plus maze, open field and vital signs tests. The combined targets of PD and SMFs were detected using RNA-sequencing (RNA-seq). The results showed that the antitumor effect of 22 Tesla (T) SMF group was 3.6-fold higher compared with that of the 2 mg/kg PD group (tumor growth inhibition=10.08%), while the antitumor effect of 150 mT SMF was only 1.56-fold higher compared with that of PD. Although PD reduced the food intake, there was no significant difference in body weight, water intake or food consumption among PD and SMF groups. Behavioral results indicated that PD ameliorated dysphoria in mice, but SMFs reduced this effect. However, no significant abnormalities were found in routine blood, blood biochemistry test, H&E staining or organ index, except renal index which was reduced by PD with or without SMFs. RNA-sequencing (RNA-seq) demonstrated that SMFs and PD synergistically targeted the expression of genes associated with tumor growth, inflammation and neurological disease. The present study showed the antitumor efficacy and biosafety of moderate or ultra-high SMF combined with PD, which exhibited only few side effects in the treatment of lung cancer, thus supporting further research for the clinical application of magnetic fields.

An environmentally insensitive fluorescent probe for G4 DNA detection: Design, synthesis, and mechanism studies.

G4 DNA structure highly localized to functionally important sites within the human genome, has been identified as a biomarker for regulation of multiple biological processes. Identification G4-responsive fluorescence probes has broad application prospects for addressing G4 biological functions, as well as developing of new families of anticancer drugs. However, some currently designed G4 DNA probes may suffer from serious solvent-dependent effect, and cause unspecific fluorescence that masks the specific signal from G4 DNA. Herein, with a bulky imidazole-cored molecular rotor fusing in D-A building block of carbazole-pyridinium, we constructed a new probe ACPS. This new probe with desirable environmentally insensitive property exhibited a "fluorescence-off" state in various polarity solvents. In the presence of G4 DNA, the intra-molecular rotations would be restricted, triggering intense fluorescence enhancement. Especially, probe ACPS bound to G4 DNA structures with superior selectivity, exhibiting much weaker fluorescence response in the presence of non-G4 DNA structures. This probe was also able to realize fluorescence visualization in cell imaging. Collectively, the probe design strategy eliminates the background fluorescence caused by uncontrollable environmental polarity change, thereby achieving high-fidelity sensing G4 DNA structures in complicated systems.

Screen-printed highly stretchable and stable flexible electrodes with a negative Poisson's ratio structure for supercapacitors.

Flexible power sources are crucial to developing flexible electronic systems; nonetheless, the current poor stretchability and stability of flexible power sources hinder their application in such devices. Accordingly, the stretchability and fatigue stability of flexible power sources are crucial for the practical application of flexible electronic systems. In this work, a flexible electrode with an arc-shaped star concave negative Poisson's ratio (NPR) structure is fabricated through the screen printing process. Using the combination of finite element analysis (FEA) and tensile tests, it is proven that the arc-shaped star concave NPR electrode can effectively reduce the maximum tensile stress and increase the maximum elongation (maximum elongation 140%). Furthermore, the flexible electrodes prepared in this study are assembled into all-solid-state symmetric supercapacitors (SSCs), and their electrochemical properties are tested. The SSC prepared in this study has a high areal capacitance of 243.1 mF cm-2. It retains 89.25% of its initial capacity after 5000 times of folding and can maintain a stable output even in extreme deformation, which indicates that the SSC prepared in this study has excellent stability. The SSC with the advantages mentioned above obtained in this study is expected to provide new opportunities to develop flexible electronic systems.

Structural Identification of Lipid-α: A Glycosyl Lipid Involved in Oligo- And Polysaccharides Metabolism in Streptococcus agalactiae (Group B Streptococcus).

Streptococcus agalactiae (group B Streptococcus, GBS) is a gram-positive bacterium that is an asymptomatic colonizer commonly found in the gastrointestinal and genitourinary tract of healthy adults. GBS is also the most common cause of life-threatening bacterial infections in newborns and is emerging as a pathogen in immunocompromised and diabetic adults. The GBS cell wall and covalently linked capsular polysaccharides (CPS) are vital to the protection of the bacterial cell and act as virulence factors. GBS-CPS have been successfully used to produce conjugate vaccines for all currently identified GBS serotypes. However, the mechanisms of biosynthesis and assembly of CPS and the other cell wall components remain poorly defined due to their complex surface structures. In this biosynthetic study of the GBS cell wall-CPS complex, glycolipids with varying lengths of glycosyl-chains were discovered. Among those, one of the smallest glycolipids (named GBS Lipid-α) was structurally characterized. Lipid-α is involved in GBS saccharide metabolism and presumably acts as a glycosyl acceptor to elongate the glycosyl chain. GBS Lipid-α was determined to be a 3-monosaccharide 1,2 acyl glycerol with a molecular mass in the range of m/z = 724-808. GBS Lipid-α is highly heterogenic with various acyl groups and glycosyl moieties. This knowledge will pave the way for future studies to elucidate the entire metabolic pathway and genes involved. The Lipid-α pathway may also exist in other bacterial species and has the potential to be a biomarker for future drug development.

Selective c-MYC G4 DNA recognition based on a fluorescent light-up probe with disaggregation-induced emission characteristics.

The c-MYC promoter is well-known as an important oncogene, the overexpression of which leads to ∼80% of all solid tumors. The four-stranded G4 present in the c-MYC promoter has been shown to play a pivotal role in the regulation of c-MYC transcription. Accordingly, strategies employed for c-MYC G4 DNA sensing have implications for the detection of many human pathologies. However, achieving specificity toward c-MYC G4 over other structurally similar G4s is a challenging task. Here, a supramolecular strategy that relies on the recognition-driven disaggregation of a novel BODIPY probe is outlined. The synthesized probe remained almost non-fluorescent in aqueous media in the aggregation state. Of all the tested G4 and non-G4 DNAs, only c-MYC triggered probe disaggregation and induced a significant increase in fluorescence intensity. The binding details discussed here suggest the basis for the recognition of a particular G4 structure, thus opening up a new way for the design and development of sequence-selective supramolecular G4 probes with desired properties.

Tesla Valve-Based Flexible Microhybrid Chip with Unidirectional Flow Properties.

Flexible microfluidic chips have good application prospects in situations with easy bending and complex curvature. An important factor affecting the flexible microfluidic chip is its structural complexity. For example, the hybrid chip includes flow channels, mixing chambers, and one-way valves. How to achieve the same function with as few structures as possible has become an important research topic at present. In this paper, a Tesla valve micromixer with unidirectional flow characteristics is presented. A passive laminar flow Tesla valve micromixer is fabricated through 3D printing technology and limonene dissolution method. The main process is as follows: First of all, high impact polystyrene (HIPS) material was employed to make the Tesla valve channel mold. Second, the channel mold was dissolved in the limonene solvent. The mold of Tesla micromixer is made of HIPS material, the mixing experiment displace that the Tesla valve micromixer is characterized by unidirectional flow compared with the common T-shaped planar channel. At the same time, the 5-AAC Tesla valve micromixer can increase the mixing efficiency to 87%. By using four different groove structures and different flow rates of the mixing effect experiment, the conclusion is that the mixing efficiency of the 6-AAC Tesla valve micromixer is up to 0.89 when the flow rate is 2 mL/min. The results manifest that the Tesla valve structure can effectively improve the mixing efficiency.

[Corrigendum] 3­Bromopyruvate sensitizes human breast cancer cells to TRAIL­induced apoptosis via the phosphorylated AMPK­mediated upregulation of DR5.

Following the publication of this article, an interested reader drew to the authors' attention that the western blotting data shown in Fig. 3 on. p. 2439 contained apparent anomalies; first, the protein bands shown to represent the CHOP and p­AMPK experiments in Fig. 3A were strikingly similar. Secondly, the same data bands were inadvertently included in the figure to represent the GRP78 and Bax experiments for the MCF­7 group. The authors have re­examined their original data and realized that this figure was assembled incorrectly (the CHOP and GRP78 data were inadvertently duplicated in the figure). The corrected version of Fig. 3, showing the correct data for the p­AMPK and Bax experiments for the MCF­7 group in Fig. 3A, is shown on the next page. The authors sincerely apologize for the error that was introduced during the preparation of this figure, thank the Editor of Oncology Reports for granting them the opportunity to publish a Corrigendum, and are grateful to the reader for alerting them to this issue. The authors also regret any inconvenience that this mistake may have caused. [the original article was published in Oncology Reports 40: 2435­2444, 2018; DOI: 10.3892/or.2018.6644].

Microscopic Observation of Preferential Capillary Pumping in Hollow Nanowire Bundles.

Numerous studies have focused on designing micro/nanostructured surfaces to improve wicking capability for rapid liquid transport in many industrial applications. Although hierarchical surfaces have been demonstrated to enhance wicking capability, the underlying mechanism of liquid transport remains elusive. Here, we report the preferential capillary pumping on hollow hierarchical surfaces with internal nanostructures, which are different from the conventional solid hierarchical surfaces with external nanostructures. Specifically, capillary pumping preferentially occurs in the nanowire bundles instead of the interconnected V-groove on hollow hierarchical surfaces, observed by confocal laser scanning fluorescence microscopy. Theoretical analysis shows that capillary pumping capability is mainly dependent on the nanowire diameter and results in 15.5 times higher capillary climbing velocity in the nanowire bundles than that in the microscale V-groove. Driven by the Laplace pressure difference between nanowire bundles and V-grooves, the preferential capillary pumping is increased with the reduction of the nanowire diameter. Capillary pumping of the nanowire bundles provides a preferential path for rapid liquid flow, leading to 2 times higher wicking capability of the hollow hierarchical surface comparing with the conventional hierarchical surface. The unique mechanism of preferential capillary pumping revealed in this work paves the way for wicking enhancement and provides an insight into the design of wicking surfaces for high-performance capillary evaporation in a broad range of applications.

Self-trapped exciton emission in an Sn(II)-doped all-inorganic zero-dimensional zinc halide perovskite variant.

The toxicity of Pb in conventional perovskites impedes the commercialization of their optoelectronic devices. Therefore, the search for comparable Pb-free perovskites is vital and needs urgent attention. Herein, for the first time, we successfully synthesize the Sn(II)-doped Pb-free zinc-based perovskite variant Cs2ZnCl4. The influence of doping is investigated both experimentally and theoretically. Broad bright red emission with a large Stokes shift is observed and attributed to the self-trapped exciton (STE) emission of the doped disphenoidal [SnCl4]2- units in the host matrix, from 3P1 to 1S0. Temperature-dependent photoluminescence (PL) shows a peak split at cryogenic temperature, which is ascribed to the Jahn-Teller effect of the 3P1 state. Theoretical study reveals that the impurity states of Sn2+ shrink the bandgap and localize the band edges, and distortion of [SnCl4]2- under excitation ultimately leads to the STE emission. This work is significant for STE emission studies and will pave a way for Pb-free perovskite variants in illumination applications.

Performance of Plasma HSP90α, Serum EBV VCA IgA Antibody and Plasma EBV DNA for the Diagnosis and Prognosis Prediction of Nasopharyngeal Carcinoma.

OBJECTIVE: The aim of this study was to evaluate the effectiveness of Epstein-Barr virus (EBV) VCA-IgA antibody, EBV DNA and HSP90α alone or in combinations for the diagnosis and prognostic prediction of nasopharyngeal carcinoma (NPC). METHODS: A total of 113 treatment-naïve patients with NPC and 40 healthy controls were enrolled. Plasma HSP90α and serum EBV VCA IgA antibody were detected using ELISA, and plasma EBV DNA was quantified using qPCR assay. The effectiveness of plasma HSP90α level, serum EBV VCA IgA antibody and plasma EBV DNA was examined in the diagnosis and prognosis prediction of NPC. RESULTS: Higher plasma HSP90α, serum EBV VCA IgA antibody and plasma viral load of EBV DNA were detected in NPC patients than in healthy controls (P < 0.001). The plasma HSP90α levels, serum EBV VCA IgA antibody titers and plasma viral load of EBV DNA were significantly greater in NPC patients with stages III and IV than in those with stages I and II (P < 0.001), and significantly lower plasma HSP90α levels, serum EBV VCA IgA antibody titers and plasma viral load of EBV DNA were found in the good prognosis group than in the poor prognosis group post-treatment (P < 0.05). The area under representative operating curves (AUCs) of plasma HSP90α, serum EBV VCA IgA antibody and plasma EBV DNA alone and in combination were 0.884, 0.841, 0.934 and 0.954 for the diagnosis of NPC, respectively. Univariate and multivariate Cox proportional hazards regression analyses identified HSP90α as an independent prognostic factor for NPC. CONCLUSION: The combination of plasma HSP90α, serum EBV VCA IgA antibody and plasma EBV DNA shows high diagnostic performance for NPC, and plasma HSP90α may be a potential marker for diagnosis and prognosis prediction of NPC.

Lobetyolin inhibits the proliferation of breast cancer cells via ASCT2 down-regulation-induced apoptosis.

This study aimed to investigate the anti-cancer effect of lobetyolin on breast cancer cells. Lobetyolin was incubated with MDA-MB-231 and MDA-MB-468 breast cancer cells for 24 h. Glucose uptake and the mRNA expression of GLUT4 (SLC2A4), HK2 and PKM2 were detected to assess the effect of lobetyolin on glucose metabolism. Glutamine uptake and the mRNA expression of ASCT2 (SLC1A5), GLS1, GDH and GLUL were measured to assess the effect of lobetyolin on glutamine metabolism. Annexin V/PI double staining and Hoechst 33342 staining were used to investigate the effect of lobetyolin on cell apoptosis. Immunoblot was employed to estimate the effect of lobetyolin on the expression of proliferation-related markers and apoptosis-related markers. SLC1A5 knockdown with specific siRNA was performed to study the role of ASCT2 played in the anti-cancer effect of lobetyolin on MDA-MB-231 and MDA-MB-468 breast cancer cells. C-MYC knockdown with specific siRNA was performed to study the role of c-Myc played in lobetyolin-induced ASCT2 down-regulation. Myr-AKT overexpression was performed to investigate the role of AKT/GSK3ß signaling played in lobetyolin-induced down-regulation of c-Myc and ASCT2. The results showed that lobetyolin inhibited the proliferation of both MDA-MB-231 and MDA-MB-468 breast cancer cells. Lobetyolin disrupted glutamine uptake via down-regulating ASCT2. SLC1A5 knockdown attenuated the anti-cancer effect of lobetyolin. C-MYC knockdown attenuated lobetyolin-caused down-regulation of ASCT2 and Myr-AKT overexpression reversed lobetyolin-caused down-regulation of both c-Myc and ASCT2. In conclusion, the present work suggested that lobetyolin exerted anti-cancer effect via ASCT2 down-regulation-induced apoptosis in breast cancer cells.

Genome-wide characterization of bZIP transcription factors and their expression patterns in response to drought and salinity stress in Jatropha curcas.

The basic leucine zipper (bZIP) family is one of the largest families of transcription factors (TFs) in plants and is responsible for various functions, including regulating development and responses to abiotic/biotic stresses. However, the roles of bZIPs in the regulation of responses to drought stress and salinity stress remain poorly understood in Jatropha curcas L., a biodiesel crop. In the present study, 50 JcbZIP genes were identified and classified into ten groups. Cis-element analysis indicated that JcbZIP genes are associated with abiotic stress. Gene expression patterns and quantitative real-time PCR (qRT-PCR) showed that four JcbZIP genes (JcbZIPs 34, 36, 49 and 50) are key resistance-related genes under both drought and salinity stress conditions. On the basis of the results of cis-element and phylogenetic analyses, JcbZIP49 and JcbZIP50 are likely involved in responses to drought and salinity stress; moreover, JcbZIP34 and JcbZIP36 might also play important roles in seed development and response to abiotic stress. These findings advance our understanding of the comprehensive characteristics of JcbZIP genes and provide new insights for functional validation in the further.