Revealing tumor cells and tissues with high selectivity through folic acid-targeted nanofluorescence probes responsive to acidic microenvironments.

Tumor-specific fluorescent probes must fulfill the dual requirements of targeted accumulation within tumors and high-resolution imaging capabilities. To achieve both tumor-targeted accumulation and high-resolution imaging performance, we developed a composite comprising an acid-responsive bodipy conjugated to amphiphilic PEG-b-PLA polymer, along with folic acid (FA)-modified PEG-b-PLA as a targeting moiety for active tumor-specific accumulation. Finally, a novel assembly of hybrid fluorescent nanoparticles was successfully synthesized by integrating these two components, demonstrating exceptional responsiveness to acidic conditions for fluorescence excitation and remarkable tumor-targeted accumulation capabilities. We conducted comprehensive in vitro and in vivo investigations employing techniques such as analysis of physicochemical properties, fluorescence-based probes detection at varying pH levels, assessment of in vitro cytotoxicity, evaluation of cellular uptake capacity, analysis of lysosomal co-localization imaging, examination of tumor fluorescence images in vivo, and investigation of biological distribution patterns. The results demonstrated that the acid-responsive nanofluorescence probe we designed and synthesized possesses desirable physical and chemical characteristics, including a small particle size and low cytotoxicity. Moreover, it exhibits rapid real-time response to acidic environments and displays enhanced fluorescence intensity, enabling the real-time tracking of probe entry into tumor cells as well as intracellular lysozyme accumulation. We achieved highly specific in vivo tumor visualization by combining nanoprobes targeting folate receptor. Through imaging cervical tumor mice, we demonstrated the precise imaging performance and high targeted accumulation of FA-targeted nanofluorescence probes in tumor tissue. Furthermore, we confirmed the in vivo safety of the FA-targeted nanofluorescence probe through biological distribution analysis. These findings highlight the potential widespread application of FA-targeted acid-responsive nanofluorescence probes for selective imaging of tumor cells and tissues.

Knockdown of ABHD11­AS1 prevents the procession of TNBC by upregulating miR­199a­5p.

Breast cancer (BC) has become a threat to women's health. In addition, patients with triple-negative BC (TNBC) have the worst prognosis among all patients with BC. Furthermore, long non-coding RNA ABHD11-AS1 is aberrantly highly expressed in TNBC, suggesting that RNA ABHD11-AS1 may serve as an important role in the progression of TNBC. However, the detailed function of ABHD11-AS1 in TNBC remains largely unknown. The levels of ABHD11-AS1 in MDA-MB-231 cells were assessed by reverse transcription-quantitative PCR. To investigate the effect of ABHD11-AS1 on the progression of TNBC, a xenograft animal model was established. Knockdown of ABHD11-AS1 inhibited the epithelial-mesenchymal transition and migration of TNBC cells. In addition, ABHD11-AS1 promoted the viability and migration of TNBC cells by upregulating microRNA (miR)-199a-5p. Furthermore, knockdown of ABHD11-AS1 suppressed TNBC tumor growth in vivo by upregulating miR-199a-5p. In conclusion, knockdown of ABHD11-AS1 suppressed the progression of TNBC via upregulation of miR-199a-5p. The data of the present study may provide novel directions and a theoretical basis for TNBC treatment.

An integrated and scalable experimental system for nitrogen-vacancy ensemble magnetometry.

Nitrogen-vacancy (NV) centers in diamond are extremely promising solid-state spin quantum sensors for magnetic field in recent years. The rapid development of NV-ensemble magnetometry has put forward higher requirements for high-speed data acquisition, real-time signal processing and analyzing, etc. However, the existing commercial instruments are bulky and expensive, which brings extra complexity to the weak magnetic field detection experiment and hinders the practicality and miniaturization of NV-ensemble magnetometry. Here, we report on an integrated and scalable experimental system based on a field-programmable-gate-array (FPGA) chip assisted with high-speed peripherals for NV-ensemble magnetometry, which presents a compact and compatible design containing high-speed data acquisition, oscilloscopes, signal generator, spectrum analyzer, lock-in amplifier, proportional-integral-derivative feedback controller, etc. To verify its applicability and reliability in experiments, various applications, such as optical magnetic resonance detection, optical cavity locking, and lock-in NV magnetometry, are conducted. We further realize the pump-enhanced magnetometry based on NV center ensembles using the optical cavity. Through the flexible FPGA design approach, this self-developed device can also be conveniently extended into atomic magnetometer and other quantum systems.

Synchronized time tagger for single-photon detection in one- and two-dimension quantum experiments.

We report a synchronized time tagger based on a field-programmable-gate-array chip for one- or two-dimensional quantum experiments that require precise single-photon detections. The time tagger has a 9.2 ps single-shot root-mean-square precision and is equipped with a 1 GB dynamic memory for data storage. Because the relationship between the control parameter and acquired data is guaranteed by using hardware synchronization, the experiment can be performed much faster than conventional schemes that are based on software synchronization. With this technique, an improvement of up to 61.3% in efficiency is observed in a typical nitrogen-vacancy center quantum experiment. We further show advanced optical features of the center using the detected high-resolution photon-arrival information and provide detailed electrical benchmarking of the device. This technique could be easily extended to other quantum control systems.

Progerin modulates the IGF-1R/Akt signaling involved in aging.

Progerin, a product of LMNA mutation, leads to multiple nuclear abnormalities in patients with Hutchinson-Gilford progeria syndrome (HGPS), a devastating premature aging disorder. Progerin also accumulates during physiological aging. Here, we demonstrate that impaired insulin-like growth factor 1 receptor (IGF-1R)/Akt signaling pathway results in severe growth retardation and premature aging in Zmpste24-/- mice, a mouse model of progeria. Mechanistically, progerin mislocalizes outside of the nucleus, interacts with the IGF-1R, and down-regulates its expression, leading to inhibited mitochondrial respiration, retarded cell growth, and accelerated cellular senescence. Pharmacological treatment with the PTEN (phosphatase and tensin homolog deleted on chromosome 10) inhibitor bpV (HOpic) increases Akt activity and improves multiple abnormalities in Zmpste24-deficient mice. These findings provide previously unidentified insights into the role of progerin in regulating the IGF-1R/Akt signaling in HGPS and might be useful for treating LMNA-associated progeroid disorders.

Mitigative Effects of PFF-A Isolated from Ecklonia cava on Pigmentation in a Zebrafish Model and Melanogenesis in B16F10 Cells.

Melanin synthesis is a defense mechanism that prevents skin damage, but excessive accumulation of melanin occurs in the skin in various reactions such as pigmentation, lentigines, and freckles. Although anti-melanogenic effects have been demonstrated for various naturally occurring marine products that inhibit and control tyrosinase activity, most studies have not been extended to in vivo applications. Phlorofucofuroeckol-A (PFF-A, 12.5-100 µM) isolated from Ecklonia cava has previously been shown to have tyrosinase-mitigative effects in B16F10 cells, but it has not been evaluated in an in vivo model, and its underlying mechanism for anti-melanogenic effects has not been studied. In the present study, we evaluated the safety and efficacy of PFF-A for anti-melanogenic effects in an in vivo model. We selected low doses of PFF-A (1.5-15 nM) and investigated their mitigative effects on pigmentation stimulated by α-MSH in vivo and their related-mechanism in an in vitro model. The findings suggest that low-dose PFF-A derived from E. cava suppresses pigmentation in vivo and melanogenesis in vitro. Therefore, this study presents the possibility that PFF-A could be utilized as a new anti-melanogenic agent in the cosmeceutical industries.

Identification of Key Prognostic-Related miRNA-mRNA Pairs in the Progression of Endometrial Carcinoma.

OBJECTIVES: Endometrial carcinoma (EC) is one of the leading causes of death from gynecological cancer due to the high recurrence rate. However, the molecular mechanisms of EC progression are not well understood. This study aimed to identify critical genes and miRNAs associated with the progression and prognosis of EC and find the potential mRNA-miRNA regulatory relationship. DESIGN: The mRNA and miRNA data were downloaded from The Cancer Genome Atlas (TCGA) database. Next, differentially expressed genes (DEGs) were identified. Subsequently, prognosis-related genes and miRNAs were identified, followed by co-expression analysis of these mRNAs and miRNAs. Materials, Setting, and Methods: Samples in the mRNA microarray were divided into normal (n = 35), early stage (n = 385), and advanced stage (n = 153). Next, DEGs in normal versus early stage and early stage versus advanced stage were, respectively, identified, followed by Venn analysis to screen overlapping DEGs in 2 comparison groups. Based on the expression level of these DEGs, univariate Cox regression analysis and Kaplan-Meier method were performed to obtain prognosis-related genes. Moreover, genes-related miRNAs were predicted, and miRNA-mRNA co-expressed pairs were identified. Then, survival analysis of co-expressed miRNA was performed. Finally, co-expressed genes of key genes were identified, and then functional enrichment analysis was conducted. RESULTS: After integrating analysis, 326 overlapping (309 upregulated and 17 downregulated) DEGs were obtained. Univariate Cox regression analysis showed that 44 mRNAs and 8 miRNAs were associated with the prognosis of EC. Combined with the co-expressed analysis, only one prognosis-related hsa-miR-326/ELFN2 axis was obtained. In addition, functional enrichment analysis showed that co-expressed genes of ELFN2 were mainly involved in the PI3K-Akt signaling pathway. LIMITATIONS: These findings were obtained via bioinformatics analysis, and thus further experimental studies are urgently demanded to validate our results. CONCLUSIONS: One key miRNA-mRNA regulatory pair (hsa-miR-326-ELFN2) was screened. This study provided a bioinformatics basis for the molecular mechanism of EC progression and might contribute to the identification of novel therapeutic targets.

Finite-time stability and optimal control of an impulsive stochastic reaction-diffusion vegetation-water system driven by Lévy process with time-varying delay.

In this paper, a reaction-diffusion vegetation-water system with time-varying delay, impulse and Lévy jump is proposed. The existence and uniqueness of the positive solution are proved. Meanwhile, mainly through the principle of comparison, we obtain the sufficient conditions for finite-time stability which reflect the effect of time delay, diffusion, impulse, and noise. Besides, considering the planting, irrigation and other measures, we introduce control variable into the vegetation-water system. In order to save the costs of strategies, the optimal control is analyzed by using the minimum principle. Finally, numerical simulations are shown to illustrate the effectiveness of our theoretical results.

Near-optimal control and threshold behavior of an avian influenza model with spatial diffusion on complex networks.

Near-optimization is as sensible and important as optimization for both theory and applications. This paper concerns the near-optimal control of an avian influenza model with saturation on heterogeneous complex networks. Firstly, the basic reproduction number $ \mathcal{R}_{0} $ is defined for the model, which can be used to govern the threshold dynamics of influenza disease. Secondly, the near-optimal control problem was formulated by slaughtering poultry and treating infected humans while keeping the loss and cost to a minimum. Thanks to the maximum condition of the Hamiltonian function and the Ekeland's variational principle, we establish both necessary and sufficient conditions for the near-optimality by several delicate estimates for the state and adjoint processes. Finally, a number of examples presented to illustrate our theoretical results.

Urine Biomarkers for the Diagnosis of Bladder Cancer: a Network Meta-Analysis.

PURPOSE: To identify effective urine biomarkers for bladder cancer diagnosis. MATERIALS AND METHODS: This meta-analysis was conducted following the guidelines of the Meta-Analyses (PRISMA) statement. Relevant studies were searched from the PubMed, Embase, and Cochrane Library databases. Heterogeneity tests were performed using Q statistics and I2 tests to determine the use of the random or fixed effects model. A direct comparison meta-analysis and network meta-analysis were conducted. The effect values are presented as odds ratios and 95% confidence intervals. Sensitivity analysis and consistency tests were performed. RESULTS: Fifty-eight studies with 12,038 participants were included. Direct comparison meta-analysis showed statistically significant differences in bladder cancer antigen (BTA) trak vs. nuclear matrix protein 22 (NMP22), BTA stat vs. urine cytology (UC), and fluorescence in situ hybridization (FISH) vs. UC, among the sensitivity indicators. Among the specificity indicators, there were statistically significant differences in BTA trak vs. UC, ImmunoCyt (immunocyte) vs. NMP22, and BTA stat vs. FISH. Among the positive predictive indicators, NMP22 vs. UC, BTA stat vs. UC, and FISH vs. NMP22 showed statistically significant differences. Among the negative predictive indicators, the differences in FISH vs. UC, FISH vs. NMP22, and hyaluronidase 1 (HYAL-1) vs. UC were statistically significant. Among the accuracy indicators, FISH vs. NMP22, FISH vs. UC, and HYAL-1 vs. UC showed statistically significant differences. Network meta-analysis showed that HYAL-1, urothelial carcinoma associated 1 (UCA1) and survivin had the highest sensitivity, while UC had the lowest sensitivity. The specificity of UC, FISH, and HYAL-1 was the highest, while that of UCA1 was the lowest. In terms of positive predictive indicators, UC, FISH, and HYAL-1 had the highest positive predictive value, while the BTA group had the lowest positive predictive value. In terms of negative predictive indicators, HYAL-1, UCA1, and survivin had the highest negative predictive value, while UC had the lowest negative predictive value. In terms of accuracy indicators, HYAL-1, UCA1, and survivin had the highest accuracy, while UC had the lowest accuracy. CONCLUSION: HYAL-1 and survivin are suitable urine biomarkers for bladder cancer diagnosis.

The asymptotic stability of numerical analysis for stochastic age-dependent cooperative Lotka-Volterra system.

In this study, we explore a stochastic age-dependent cooperative Lotka-Volterra (LV) system with an environmental noise. By applying the theory of M-matrix, we prove the existence and uniqueness of the global solution for the system. Since the stochastic age-dependent cooperative LV system cannot be solved explicitly, we then construct an Euler-Maruyama (EM) numerical solution to approach the exact solution of the system. The convergence rate and the pth-moment boundedness of the scheme have also been obtained. Additionally, numerical experiments have been conducted to verify our theoretical results.

Ishophloroglucin A Isolated from Ishige okamurae Suppresses Melanogenesis Induced by α-MSH: In Vitro and In Vivo.

Diphlorethohydroxycarmalol (DPHC) isolated from Ishige okamurae (IO) showed potential whitening effects against UV-B radiation. However, the components of IO as well as their molecular mechanism against α-melanocyte-stimulating hormone (α-MSH) have not yet been investigated. Thus, this study aimed to investigate the inhibitory effects of Ishophloroglucin A (IPA), a phlorotannin isolated from brown algae IO, and its crude extract (IOE), in melanogenesis in vivo in an α-MSH-induced zebrafish model and in B16F10 melanoma cells in vitro. Molecular docking studies of the phlorotannins were carried out to determine their inhibitory effects and to elucidate their mode of interaction with tyrosinase, a glycoprotein related to melanogenesis. In addition, morphological changes and melanin content decreased in the α-MSH-induced zebrafish model after IPA and IOE treatment. Furthermore, Western blotting results revealed that IPA upregulated the extracellular related protein expression in α-MSH-stimulated B16F10 cells. Hence, these results suggest that IPA isolated from IOE has a potential for use in the pharmaceutical and cosmetic industries.

Accumulation of prelamin A induces premature aging through mTOR overactivation.

Hutchinson-Gilford progeria syndrome (HGPS) arises when a truncated form of farnesylated prelamin A accumulates at the nuclear envelope, leading to misshapen nuclei. Previous studies of adult Zmpste24-deficient mice, a mouse model of progeria, have reported a metabolic response involving inhibition of the mTOR (mammalian target of rapamycin) kinase and activation of autophagy. However, exactly how mTOR or autophagy is involved in progeria remains unclear. Here, we investigate this question by crossing Zmpste24+/- mice with mice hypomorphic in mTOR (mTOR△/+ ), or mice heterozygous in autophagy-related gene 7 (Atg7+/- ). We find that accumulation of prelamin A induces premature aging through mTOR overactivation and impaired autophagy in newborn Zmpste24-/- mice. Zmpste24-/- mice with genetically reduced mTOR activity, but not heterozygosity in Atg7, show extended lifespan. Moreover, mTOR inhibition partially restores autophagy and S6K1 activity. We also show that progerin interacts with the Akt phosphatase to promote full activation of the Akt/mTOR signaling pathway. Finally, although we find that genetic reduction of mTOR postpones premature aging in Zmpste24 KO mice, frequent embryonic lethality occurs. Together, our findings show that over-activated mTOR contributes to premature aging in Zmpste24-/- mice, and suggest a potential strategy in treating HGPS patients with mTOR inhibitors.

Anti-obesity effects of red seaweed, Plocamium telfairiae, in C57BL/6 mice fed a high-fat diet.

This study aimed to demonstrate the anti-obesity effect of Plocamium telfairiae (PT), a red seaweed. Different percentages of ethanol (0%, 20%, 40%, 60%, 80%, and 100%) were used for the preparation of PT extract. Furthermore, 3T3-L1 cells were used to determine the percentage of ethanol for optimal anti-adipogenesis of PT, and the anti-obesity properties of the optimized extract of PT (PTE) (40%) was assessed in obese mice. The results indicate that 40% ethanol extract (40 PTE) significantly decreased fat accumulation and suppressed the expression of major adipogenesis factors such as peroxisome proliferator-activated receptor-γ (PPAR-γ), sterol regulatory element-binding protein 1 (SREBP-1), CCAAT/enhancer-binding protein (C/EBP)-α, and phosphorylated ACC (pACC) in 3T3-L1 cells. Furthermore, in the high-fat diet-induced obese mice, 40 PTE significantly reduced the weights of white adipose tissue, as well as the levels of triglyceride, total cholesterol, adiponectin, and insulin in the serum. Liver histopathology showed that steatosis decreased in all the PTE treatment groups. The adipogenesis-related proteins, PPAR-γ and SREBP-1, were also significantly decreased in PTE treatment groups. Additionally, 40 PTE increased mRNA expression of mitochondrial uncoupling proteins (UCP)-1 and UCP-3 in brown adipose tissue. These findings provide evidence that 40 PTE can alleviate lipid droplet accumulation in 3T3-L1 adipocytes and obese C57BL/6 mice, indicating that PTE has strong anti-obesity effects and could be used as a therapeutic agent or a component of pharmaceutical drugs and functional foods.

Anti-Obesity Effects of Grateloupia elliptica, a Red Seaweed, in Mice with High-Fat Diet-Induced Obesity via Suppression of Adipogenic Factors in White Adipose Tissue and Increased Thermogenic Factors in Brown Adipose Tissue.

Obesity is a serious metabolic syndrome characterized by high levels of cholesterol, lipids in the blood, and intracellular fat accumulation in adipose tissues. It is known that the suppression of adipogenic protein expression is an effective approach for the treatment of obesity, and regulates fatty acid storage and transportation in adipose tissues. The 60% ethanol extract of Grateloupia elliptica (GEE), a red seaweed from Jeju Island in Korea, was shown to exert anti-adipogenic activity in 3T3-L1 cells and in mice with high-fat diet (HFD)-induced obesity. GEE inhibited intracellular lipid accumulation in 3T3-L1 cells, and significantly reduced expression of adipogenic proteins. In vivo experiments indicated a significant reduction in body weight, as well as white adipose tissue (WAT) weight, including fatty liver, serum triglycerides, total cholesterol, and leptin contents. The expression of the adipogenic proteins, SREBP-1 and PPAR-γ, was significantly decreased by GEE, and the expression of the metabolic regulator protein was increased in WAT. The potential of GEE was shown in WAT, with the downregulation of PPAR-γ and C/EBP-α mRNA; in contrast, in brown adipose tissue (BAT), the thermogenic proteins were increased. Collectively, these research findings suggest the potential of GEE as an effective candidate for the treatment of obesity-related issues via functional foods or pharmaceutical agents.

Colon cancer-associated transcript-1 enhances glucose metabolism and colon cancer cell activity in a high-glucose environment in vitro and in vivo.

BACKGROUND: Our study aims to investigate the effect of colon cancer-associated transcript-1 (CCAT-1) on colon cancer cells' activity and metabolism under different glucose environments in vitro and in vivo. METHODS: The levels of proliferation, migration, glucose, lactic acid, glucose metabolism-related enzymes, apoptosis genes, epithelial-mesenchymal transition (EMT) marker proteins, and PI3K/Akt/C-MYC pathway in CCAT-1-silenced SW620 cells cultured with different glucose levels were tested. Twenty BALB/C nude mice with hyperglycemia or normal blood sugar were transplanted with CCAT-1-silenced SW620 cells, blood glucose levels, lactic acid, insulin, and volume of transplanted tumor cells, the expression of EMT marker proteins, and PI3K/Akt/C-MYC pathway was detected. RESULTS: The levels of proliferation, migration, glucose, lactic acid, LDH-A, PKM2, and HK2 decreased, apoptosis increased in SW620 cells cultured with low glucose or silenced CCAT-1 (P<0.05); levels of E-cadherin and ZO-1 significantly increased, and levels of N-cadherin, vimentin, and p-Akt decreased in CCAT-1-silenced SW620 cells cultured with high glucose (P<0.05). Hyperglycemic nude mice transplanted with CCAT-1-silenced colon cancer cells showed decreased tumor volume, blood glucose, lactic acid, insulin, P-AKT, and P-C-MYC than EV group (P<0.05). CONCLUSIONS: CCAT-1 can enhance glucose metabolism and proliferation and migration of colon cancer cells by upregulating the expression of glycolysis enzymes, inhibiting apoptosis, activating the Akt/C-MYC pathway, and promoting EMT expression.

Anti-Obesity and Anti-Diabetic Effects of Ishige okamurae.

Obesity is associated with several health complications and can lead to the development of metabolic syndrome. Some of its deleterious consequences are related to insulin resistance, which adversely affects blood glucose regulation. At present, there is a growing concern regarding healthy food consumption, owing to awareness about obesity. Seaweeds are well-known for their nutritional benefits. The brown alga Ishige okamurae (IO) has been studied as a dietary supplement and exhibits various biological activities in vitro and in vivo. The bioactive compounds isolated from IO extract are known to possess anti-obesity and anti-diabetic properties, elicited via the regulation of lipid metabolism and glucose homeostasis. This review focuses on IO extract and its bioactive compounds that exhibit therapeutic effects through several cellular mechanisms in obesity and diabetes. The information discussed in the present review may provide evidence to develop nutraceuticals from IO.

Mitochondrial Pyruvate Carriers Prevent Cadmium Toxicity by Sustaining the TCA Cycle and Glutathione Synthesis.

Cadmium (Cd) is a major heavy metal pollutant, and Cd toxicity is a serious cause of abiotic stress in the environment. Plants protect themselves against Cd stress through a variety of pathways. In a recent study, we found that mitochondrial pyruvate carriers (MPCs) are involved in Cd tolerance in Arabidopsis (Arabidopsis thaliana). Following the identification of MPCs in yeast (Saccharomyces cerevisiae) in 2012, most studies have focused on the function of MPCs in animals, as a possible approach to reduce the risk of cancer developing. The results of this study show that AtMPC protein complexes are required for Cd tolerance and prevention of Cd accumulation in Arabidopsis. AtMPC complexes are composed of two elements, AtMPC1 and AtMPC2 (AtNRGA1 or AtMPC3). When the formation of AtMPCs was interrupted by the loss of AtMPC1, glutamate could supplement the synthesis of acetyl-coenzyme A and sustain the TCA cycle. With the up-regulation of glutathione synthesis following exposure to Cd stress, the supplementary pathway could not efficiently drive the tricarboxylic acid cycle without AtMPC. The ATP content decreased concomitantly with the deletion of tricarboxylic acid activity, which led to Cd accumulation in Arabidopsis. More importantly, ScMPCs were also required for Cd tolerance in yeast. Our results suggest that the mechanism of Cd tolerance may be similar in other species.

Comprehensive analysis of coexpressed long noncoding RNAs and genes in breast cancer.

AIM: To identify the differentially expressed long noncoding RNAs (lncRNAs) in breast cancer and analyze the potential roles. METHODS: RNA-sequencing data (ID: GSE52194) of breast cancer and normal breast samples were downloaded from Gene Expression Omnibus. Clean reads were aligned against the human genome hg19 using TopHat2 and assembled into transcripts using cufflinks. Protein-coding potential of transcripts with length 200 bp or more were assessed using Coding Potential Calculator, followed by alignment against human lncRNAs using Blastn. Differentially expressed lncRNAs and genes were identified using NOISeq, followed by coexpression analysis with the criterion of Pearson correlation coefficient greater than 0.99. Enrichment analysis was performed using Database for Annotation, Visualization and Integrated Discovery. RESULTS: Totally 181 differentially expressed lncRNAs and 3967 differentially expressed genes (DEG) were obtained. Besides, coexpression analysis revealed ST6GALNAC3, ST6GALNAC4, ST8SIA5 and DEDD were coexpressed with FAM9B, LINC00320, LOC100169752 and RFX5. H2AFY2 and NOL11 were coexpressed with LOC286002. ADORA2B was coexpressed with GRHPR, LOC100652909 and TEX26-AS1. CD226, FCER1A and ADORA3 were coexpressed with LINC00323 and LOC100505540. PVRL2 and CD300LB were coexpressed with C1QTNF1, CENPA, FAM22F and SNX2. The DEG were predominantly enriched in biological processes of regulation of transcription from RNA polymerase I (e.g. H2AFY2, NOL11 and DEDD) and regulation of mast cell activation (e.g. ADORA3, CD226, FCER1A, MS4A2, ADORA2B and PVRL2), as well as pathways of glycosphingolipid biosynthesis (e.g. ST6GALNAC3, ST6GALNAC4 and ST8SIA5) and peroxisome. CONCLUSION: This study revealed the potential involvement of lncRNAs in the progression of breast cancer via participating in glycosphingolipid biosynthesis pathway and regulation of transcription and mast cell activation biological processes.

Near infrared light triggered reactive oxygen species responsive nanoparticles for chemo-photodynamic combined therapy.

Currently, the strategy of combining photodynamic therapy (PDT) and chemotherapy for enhancing cancer therapeutic efficiency has aroused extensive interest. Nonetheless, weaknesses such as low local concentration, uncontrollable release of the drug, a non-suitable treatment light source, and a low response to the tumor site of PDT lead to the combined treatment effect not being ideal. Herein, we proposed simple and intelligent ROS-responsive zinc phthalocyanine sensitized TiO2 nanoparticles which conjugated with chlorambucil (CBL) (mTiO2-BCBL@ZnPC NPs) in an attempt to solve these issues. Not only were the nanoparticles triggered in near infrared radiation (NIR) for PDT with various reactive oxygen species (ROS) being generated, but the nanoparticles also realized the controllable release of CBL by H2O2, a major kind of ROS, through cleavage of the phenylboronic ester between CBL and the nanoparticle. Impressively, the controllable release of CBL under NIR irradiation showed an on-off characteristic and time dependency. In addition, the well-defined mTiO2-BCBL@ZnPC NPs with a 30 nm average diameter showed good stability and biocompatibility. The in vitro cytotoxicity studies demonstrated that the mTiO2-BCBL@ZnPC NPs were more cytotoxic under NIR irradiation than the mTiO2@ZnPC NPs and CBL, while the mTiO2-BCBL@ZnPC NPs were less cytotoxic under dark conditions. The above results implied that photo-controlled drug release is a promising choice for cancer therapy due to its high selectivity, good safety and low side-effects, and would be expected to be used in chemo-photodynamic combined therapy for improving the therapeutic efficiency.