Combined large­cell neuroendocrine carcinoma and small­cell lung cancer: A case report.

Combined large-cell neuroendocrine carcinoma (LCNEC) and small-cell lung cancer (SCLC) is extremely rare, with only a few reports available in the literature. An accurate diagnosis is difficult to make due to the overlapping clinical features between LCNEC and SCLC, and a standardized treatment option is lacking. A 53-year-old female patient was admitted to Xiaoshan Affiliated Hospital of Wenzhou Medical University (Hangzhou, China) due to symptoms of dyspnea and phlegm, with blood in the sputum. Computed tomography revealed a 52×32×26-mm irregular soft-tissue mass in the left upper lung. Pathological examination of the biopsy specimen showed a poorly differentiated neuroendocrine carcinoma with compression injury, consistent with a mixed type of large and small cell carcinoma. The patient was administered chemotherapy, radiotherapy and targeted therapy, and as of October 2023, the patient had a survival period of 29 months. LCNEC combined with SCLC is a sporadic tumor with a high potential for malignancy. Multidisciplinary treatment and close follow-up are recommended. The multidisciplinary treatment strategy used in the present study is expected to help inform future therapeutic decisions.

Overexpression of NOP58 Facilitates Proliferation, Migration, Invasion, and Stemness of Non-small Cell Lung Cancer by Stabilizing hsa_circ_0001550.

BACKGROUND: NOP58 ribonucleoprotein (NOP58) is associated with the recurrence of lung adenocarcinoma. AIMS: Few investigations concentrate on the role of NOP58 in non-small cell lung cancer (NSCLC), which is the focus of our current study. METHODS: Following transfection, the proliferation, migration, and invasion of NSCLC cells were assessed by 5- ethynyl-2'-deoxyuridine (EdU), wound healing, and transwell assays. The percentage of CD9+ cells was evaluated by flow cytometry assay. Based on target genes and binding sites predicted through bioinformatics analysis, a dual-luciferase reporter assay was performed to verify the targeting relationship between hsa_circ_0001550 and NOP58. The effect of NOP58 overexpression on hsa_circ_0001550 stability was gauged using Actinomycin D. The hsa_circ_0001550 and NOP58 expression levels, as well as protein expressions of CD44, CD133, OCT4, and SOX2 in NSCLC cells were determined by quantitative real-time PCR and Western blot, respectively. RESULTS: Hsa_circ_0001550 was remarkably up-regulated in NSCLC cell lines A549 and PC9, silencing of which weakened cell abilities to proliferate, migrate and invade, decreased CD9+ cell ratio, and diminished protein expressions of CD44, CD133, OCT4, and SOX2. NOP58 could bind to hsa_circ_0001550 and stabilize its expression, and NOP58 overexpression partially abrogated hsa_circ_0001550 knockdown-inhibited NSCLC cell proliferation, migration, invasion and stemness. CONCLUSION: Overexpression of NOP58 facilitates proliferation, migration, invasion, and stemness of NSCLC cells by stabilizing hsa_circ_0001550, hinting that NOP58 is a novel molecular target for NSCLC therapy.

The association between serum albumin and alkaline phosphatase in cancer patients.

The role of serum albumin (ALB) has been extensively studied in patients with cancer; however, research on its effect on bone metastasis in these patients remains limited. This study aimed to investigate the relationship between serum ALB and alkaline phosphatase (ALP) levels in patients with tumors. Using data from the National Health and Nutrition Examination Survey 2011 to 2018, we assessed the correlation between serum ALB and ALP levels using a weighted multivariate linear regression model, whereas a weighted generalized additive model and smooth curve fitting were used to address potential nonlinearities. A total of 1876 patients with cancer were included in our study. In the subgroup analysis stratified by sex, race/ethnicity, and liver disease, the negative correlation of ALB with ALP remained for most groups, except in blacks (ß = -1.755, 95%CI: [-3.848, 0.338], P = .103) and patients with gout (ß = -0.676, 95%CI: [-2.061, 0.709], P = .340). In black people and patients with gout, the relationship between ALB and ALP showed an inverted U-shaped curve, with an inflection point at approximately 42 g/dL. Our study showed an inverse correlation between ALB and ALP levels in most patients with tumors, but not in black patients and those with gout. The measurement of ALB levels can serve as a screening tool for bone metastases while guiding therapeutic intervention strategies.

A rare malignant mesothelioma of the tunica vaginalis testis: A case report.

Malignant mesothelioma of the tunica vaginalis testis is a rare, highly invasive urogenital malignant tumor with no specific clinical manifestations. Reported cases of this disease are limited. Therefore, an early preoperative diagnosis is difficult. The current study presents a case of malignant mesothelioma of the tunica vaginalis testis and a literature review. A 52-year-old man was admitted to Xiaoshan Affiliated Hospital of Wenzhou Medical University (Hangzhou, China) in December 2022 and underwent radical resection of the right testicle and epididymis but did not undergo radiotherapy or chemotherapy. The patient was followed up for 5 months, and no recurrence or metastasis was found. The rarity of testicular mesothelioma poses a challenge to its etiology and diagnosis, which is rarely achieved preoperatively. Malignant mesothelioma of the testicular tunica vaginalis has a poor prognosis and is not sensitive to radiotherapy or chemotherapy, requiring close postoperative follow-up. This condition is rare in clinical practice; therefore, it needs to be reported to aid clinicians' decision-making regarding diagnosis and treatment.

Current status and prospect of ZIF-based materials for breast cancer treatment.

Breast cancer, one of the three most life-threatening cancers in modern times, must be explored for treatments with low side effects and practical efficacy. Metal organic framework materials (MOFs) is made by metal ions as the center for point and organic ligands as a bridge connecting a new type of porous nano-materials, among them, the zinc base zeolite imidazole skeleton material series (ZIFs) because of its excellent biocompatibility and pH slow controlled release ability, is widely used in the tumor microenvironment in basic research and achieved remarkable curative effect. Inspired by this, in this review, we focus on the recent research progress on the application of ZIFs in the treatment of breast cancer, mainly studying the structure of ZIFs such as ZIF-8, ZIF-90 and ZIF-67 and their application in novel therapies for breast cancer treatment, such as targeted drug delivery, photothermal therapy, immunotherapy and gene therapy.We will more fully demonstrate the potential of zif in breast cancer treatment, hoping to provide an avenue for exploring breast cancer treatment.

Accumulated Lattice Strain as an Intrinsic Trigger for the First-Cycle Voltage Decay in Li-Rich 3d Layered Oxides.

Li- and Mn-rich layered oxides (LMLOs) are promising cathode materials for Li-ion batteries (LIBs) owing to their high discharge capacity of above 250 mA h g-1. A high voltage plateau related to the oxidation of lattice oxygen appears upon the first charge, but it cannot be recovered during discharge, resulting in the so-called voltage decay. Disappearance of the honeycomb superstructure of the layered structure at a slow C-rate (e.g., 0.1 C) has been proposed to cause the first-cycle voltage decay. By comparing the structural evolution of Li[Li0.2Ni0.2Mn0.6]O2 (LLNMO) at various current densities, the operando synchrotron-based X-ray diffraction results show that the lattice strain in bulk LLNMO is continuously increased over cycling, resulting in the first-cycle voltage loss upon Li-ion insertion. Unlike the LLNMO, the accumulated average lattice strain of LiNi0.8Co0.1Mn0.1O2 (NCM811) and LiNi0.6Co0.2Mn0.2O2 (NCM622) from the open-circuit voltage to 4.8 V could be released on discharge. These findings help to gain a deep understanding of the voltage decay in LMLOs.

Association of the KISS1, LIN28B, VDR and ERα gene polymorphisms with early and fast puberty in Chinese girls.

OBJECTIVES: To explore the association of KISS1, LIN28B, vitamin D receptor (VDR), and estrogen receptor α (ERα) gene polymorphisms and the risk of early with fast puberty (EFP) risk, and with hormone levels in EFP cases, in Chinese girls. METHODS: The analysis was based on the data of 141 girls with EFP and 152 girls without EFP. Clinical features were documented, and all SNP genotyping was conducted using SNaPshot method. Statistical analysis was performed to assess the association of the SNPs with EFP risk, and with hormone levels in EFP cases. RESULTS: There was a significant association between rs7759938-C polymorphism in the LIN28B gene and the risk for EFP in the recessive (TT + CT vs. CC) model (p = 0.040). Remarkably, rs5780218-delA polymorphism in the KISS1 gene and rs2234693-C polymorphism in the ERα gene were significantly associated with peak LH (luteinizing hormone) levels (p = 0.008, 0.045) and peak LH/FSH (follicle-stimulating hormone) ratio (p = 0.007, 0.006). Additionally, on 7 of the 8 variant loci the alleles associated with increased levels of both peak LH levels and peak LH/FSH ratio in EFP cases were also associated with increased CPP risk. CONCLUSIONS: Our findings indicate that rs7759938-C polymorphism in the LIN28B gene might have a protective effect on EFP susceptibility. The most striking findings of this study is that, rs5780218-delA polymorphism in the KISS1 gene and rs2234693-C polymorphism in the ERα gene influenced levels of GnRH-stimulated peak LH and LH/FSH ratio, and in general CPP risk genes might also contributes to the abnormality of hormonal levels in EFP.

High-Performance PEO-Based All-Solid-State Battery Achieved by Li-Conducting High Entropy Oxides.

A rock-salt-structured Li-conducting high entropy oxide was prepared and utilized as an active filler in a polyethylene oxide (PEO)-based solid-state composite electrolyte. X-ray diffraction and high-resolution transmission electron microscopy were adopted to analyze the crystal structure of the high entropy oxide containing 20% of Li ions (HL20). The HL20 was crystallized in the Fm3̅m space group with Li+ ions located at the center of the MO6 octahedra. The ionic conductivity of the composite membrane at 30 °C reaches 3.44 × 10-5 S cm-1. The inflection point of activation energy of the membrane with HL20 decreases by 5 °C compared with that of the pure PEO membrane. In the galvanostatic plating/stripping test, the Li||Li symmetric batteries could be cycled at a current density of 200 µA cm-2 for over 1200 h with an overpotential of 140 mV. The Li||LiFePO4 full battery could be charged/discharged at 0.5 C for 100 circles with a high capacity retention rate of 91%. Excellent rate performance is also achieved at lower temperatures and higher rates, showing the superiority of HL20 as an active filler. This work sheds light on the development of high entropy oxide as a new type of fast ionic conductor, promoting the practical application of all-solid-state batteries at a lower temperature.

Recent advances of the core-shell MOFs in tumour therapy.

Coordination chemistry has always been vital to explore the material prominence of metal-organic systems. The metal-organic chemistry plays a fundamental role in decisive structural features, which are accountable for tuning the properties of materials. Tumour therapy has become an important research field of medical treatment in the world. Metal-organic frameworks (MOFs) have attracted extensive interest in medical science research due to their large effective surface area, clear pore network, and critical catalytic performance. Compared with traditional MOF materials, MOF materials with core-shell structures have a higher loading rate and better stability, which can overcome a single function. They have been successfully used in tumour medical research and have excellent prospects for diagnosing and treating various tumours. The current review article thoroughly describes the various synthetic approaches for engineering core-shell MOF materials, the structural types, and the potential functional applications. We also discussed core-shell MOF materials for the various treatment of tumours, such as tumour chemotherapy, tumour phototherapy and tumour microenvironment anti-hypoxia therapy. In this paper, the synthesized procedures of core-shell MOFs and their applications for tumour treatment have been discussed, and their future research has prospected. The current improved strategies, challenges, and prospects are also presented because of the metal-organic chemistry governing the structural modification of core-shell MOFs for tumour therapy applications. Therefore, the present review article opens a new door for medicinal chemists to tune the structural features of the core-shell MOF materials to modulate tumour therapy with simple, low-cost materials for better human lives.

Gene Polymorphisms Associated with Central Precocious Puberty and Hormone Levels in Chinese Girls.

Central precocious puberty (CPP) is associated with adverse health outcomes in females; however, CPP pathogenesis remains unclear. In this study, we investigated the association of 20 single nucleotide polymorphisms (SNPs) in eight genes with CPP risk and hormone levels. A case-control study on 247 and 243 girls with and without CPP, respectively, was conducted at Kunming Children's Hospital, China, from September 2019 to August 2020. The genotype of the SNPs and their haplotypes were identified. Additionally, the effects of the polymorphisms on hormone levels were investigated. Three variants (rs10159082, rs7538038, and rs5780218) in KISS1 and two variants (rs7895833 and rs3758391) in SIRT1 were related to an increased CPP risk (odds ratio (OR) = 1.524, 1.507, 1.409, 1.348, and 1.737; 95% confidence interval (CI) = 1.176-1.974, 1.152-1.970, 1.089-1.824, 1.023-1.777, and 1.242-2.430, respectively). Rs3740051in SIRT1 and rs1544410 in VDR reduced CPP risk (OR = 0.689, 0.464; 95% CI, 0.511-0.928, 0.232-0.925, respectively). Rs1544410, rs7975232, and rs731236 in VDR were negatively correlated with peak follicle-stimulating hormone (FSH; ß = -2.181; P=0.045), basal FSH (ß = -0.391; P=0.010), and insulin-like growth factor (ß = -50.360; P=0.041) levels, respectively. KISS1, SIRT1, and VDR variants were associated with CPP susceptibility, and VDR SNPs influenced hormonal levels in Chinese females with CPP. In particular, VDR polymorphism rs1544410 was associated with both CPP risk and GnRH-stimulated peak FSH levels. Further functional research and large-scale genetic studies of these loci and genes are required to confirm our findings.

Effects of Multimedia Assisted Song Integrated Teaching on College Students' English Learning Interests and Learning Outcomes.

In the process of globalization, the English language not only represents British and American culture, but it has also gradually become a language used all over the world, and it has become essential for many people to learn it as a second language. Education is the century business of a nation. At the same time, to meet the needs of E generation, I generation, and touch-screen generation students, teachers are increasingly undertaking multimedia-integrated curriculum design and instruction. Teachers are no longer knowledge providers, but they are expected to provide students with a personalized learning model and guide and support them in a timely manner. This study included a sample of business students from Guilin University of technology. A total of 216 students participated in a 16-week (3 h per week, a total of 48 h) course of experimental teaching. The research results showed that 1. multimedia assisted, song integrated English teaching affected learning interest, 2. That multimedia assisted, song integrated English teaching affected learning outcomes, and 3. That learning interest had significantly positive effects on learning outcome. Based on these results, this study contributes to improving college students' English listening, speaking, reading, and writing skills via multimedia teaching, which also facilitated their interest and ability to achieve the learning outcomes.

Engineering CpG-ASO-Pt-Loaded Macrophages (CAP@M) for Synergistic Chemo-/Gene-/Immuno-Therapy.

Adoptive cell therapy by natural cells for drug delivery has achieved encouraging progress in cancer treatment over small-molecule drugs. Macrophages have a great potential in antitumor drug delivery due to their innate capability of sensing chemotactic cues and homing toward tumors. However, major challenge in current macrophage-based cell therapy is loading macrophages with adequate amounts of therapeutic, while allowing them to play a role in immunity without compromising cell functions. Herein, a potent strategy to construct a macrophage-mediated drug delivery platform loaded with a nanosphere (CpG-ASO-Pt) (CAP) composed of functional nucleic acid therapeutic (CpG-ASO) and chemotherapeutic drug cisplatin (Pt) is demonstrated. These CAP nanosphere loaded macrophages (CAP@M) are employed not only as carriers to deliver this nanosphere toward the tumor sites, but also simultaneously to guide the differentiation and maintain immunostimulatory effects. Both in vitro and in vivo experiments indicate that CAP@M is a promising nanomedicine by macrophage-mediated nanospheres delivery and synergistically immunostimulatory activities. Taken together, this study provides a new strategy to construct a macrophage-based drug delivery system for synergistic chemo-/gene-/immuno-therapy.

Effects of Konjaku Flour on the Gut Microbiota of Obese Patients.

Objective: Gut microbiota have been thought to play a role in the emergence of obesity and metabolic disorders, thus dietary fiber may be an effective strategy for the management of obesity by modulating the gut microbiota. The aim of the present study was to investigate the effects of konjaku flour (KF) supplementation on treating obesity and regulating intestinal microbiota in obese adults. Methods: In a 5-week, randomized, double-blind, place-controlled trial, sixty-nine obese volunteers aged 25 to 35 with body mass index ≥28 kg/m2 were randomly assigned to receive KF or placebo (lotus root starch). Obesity index, blood parameters, and gut microbiota were analyzed. Results: KF remarkably reduced the body mass index (BMI), fat mass, percentage body fat (PBF), serum triglyceride (TG), glycated hemoglobin A1c (HbA1c), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels in the patients (p <0.05 or p <0.01). Meanwhile, high-throughput sequencing and bioinformatics analysis showed that the konjac flour treatment notably increased the α-diversity and changed the ß-diversity of intestinal microflora in patients (p <0.01). Moreover, konjac flour could also evidently increase the abundance of some of the beneficial microorganisms related to obesity of patients, such as Lachnospiraceae, Roseburia, Solobacterium, R. inulinivorans, Clostridium perfringens, and Intestinimonas butyriciproducens, and reduce the abundance of the harmful microorganisms, such as Lactococcus, Bacteroides fragilis, Lactococcus garvieae, B. coprophilus, B. ovatus, and B. thetaiotaomicron (p <0.01). Specifically, C. perfringens was significantly negatively correlated with serum total cholesterol (TC) (p <0.01). Conclusion: These results suggested that KF can achieve positive effects on treating obesity, which manifest on reducing BMI, fat mass, blood glucose, and blood lipid, improving hepatic function, and also regulating intestinal microfloral structure. Therefore, changes in gut microbiota may explain in part the effects of KF.

Inverted Pyramid Morphology Control by Acid Modification and Application for PERC Solar Cells.

Silicon inverted pyramid (IP) structures, with lower reflectance and increased surface recombination, are one of the best choices for light-trapping structures of high-efficiency silicon solar cells. The solution process of IP generally goes through three main steps: porous silicon etched by metal-assisted chemical etching, acid etching, and alkali anisotropic etching. In this paper, the role that acid modification plays in IP preparation and the application of our optimized texture for passivated emitter and rear solar cells (PERC) were investigated. Experimental results show that acid plays a decisive role in optimizing and modifying the morphology of porous silicon; thus, the morphology of porous silicon has no direct influence on the morphology of IP. In addition, the opening size of IP is mainly determined by the size of silicon micron holes modified by the acid process. PC1D simulation results manifest that IPs can increase the short-circuit current density (J sc) of devices by 1.04 mA/cm2 and power conversion efficiency by 0.55%; hence, our optimized IP-based PERC achieve the highest simulative conversion efficiency of 23.21%. This is an effective and important way to manipulate the structure of IP, which points out the direction of fabrication and application of high-efficiency IP textures.

Similarity and difference of pathogenesis among lung cancer subtypes suggested by expression profile data.

Lung cancer is difficult to diagnose, has a high mortality rate and a high recurrence rate. By grouping and analyzing the gene expression in lung cancer samples, we selected the differentially expressed genes (DEGs) in total lung cancers or each subgroup, and then searched for the similarities and differences among these. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed, in addition to predictable cell proliferation or immune-related pathways, 'hemostasis', 'coagulation' and 'viral myocarditis' were also enriched in common DEGs, while specific functions or pathways were enriched in different subgroups. This may have implications for the treatment of total lung cancer or different subtypes. Through bioinformatics analysis, hub genes were obtained from total lung cancer and each subgroup respectively. Survival analysis of common hub genes led us to find that ZWINT, A2M, POLR2H and KIF11 are associated with unclassified lung cancer survival. For the construction of miRNA regulatory network, miR-16-5p was related to all of these four genes, and its expression is significantly different between lung cancers and normal samples. Combined with the hub genes of each subtype, it may have the ability of early screening and typing.

Gastrointestinal Autonomic Neuropathy Exacerbates Gut Microbiota Dysbiosis in Adult Patients With Type 2 Diabetes Mellitus.

OBJECTIVE: The diabetic autonomic neuropathy is one of the most common complications in type 2 diabetes mellitus (T2DM), especially gastrointestinal autonomic neuropathy (GAN), which occurs in up to 75% of patients. The study aimed to investigate the gut microbiota composition, structure, and function in T2DM patients with GAN (T2DM_GAN) and set up a link between gut microbiota and clinical characteristics of patients. METHODS: DNA was extracted from fecal samples of three groups using the kit method: healthy volunteers (n = 19), the patients with T2DM (n = 76), and T2DM_GAN (n = 27). Sequencing of 16S ribosomal DNA was performed using the MiSeq platform. RESULTS: According to the clinical data, higher age, lower triglyceride, and lower body mass index were the main features of patients with T2DM_GAN. The gut microbiota analysis showed that Bacteroidetes, Firmicutes, and Proteobacteria constituted the three dominant phyla in healthy individuals. In addition, the gut microbiota structure and function of T2DM_GAN patients were clearly different from that of T2DM patients. T2DM patients were characterized by Fusobacteria, Fusobacteriia, Fusobacteriales, Fusobacteriaceae, Fusobacterium, Lachnoclostridium, and Fusobacterium_mortiferum. Those gut microbiota may be involved in carotenoid and flavonoid biosyntheses. Relatively, the Gammaproteobacteria, Enterobacteriales, Enterobacteriaceae, Escherichia-Shigella, Megasphaera, Escherichia_coli, and Megasphaera_elsdenii were characteristic in the T2DM_GAN patients. Those may be involved in bacterial invasion of epithelial cells and pathogenic Escherichia coli infection. CONCLUSIONS: GAN exacerbated gut microbiota dysbiosis in adult patients with T2DM. The findings indicated that phyla Fusobacteria and class Gammaproteobacteria were closely related to the occurrence of T2DM. Especially the latter may promote T2DM_GAN.

Tuning morphology, composition and oxygen reduction reaction (ORR) catalytic performance of manganese oxide particles fabricated by γ-radiation induced synthesis.

A γ-radiation induced synthesis method is used to fabricate manganese oxide catalysts through both reduction and oxidation routes. It is shown that the morphology, composition and electrochemical performance of the produced manganese oxide particles can be tuned by altering the redox conditions. The catalysts prepared via radiolytic oxidation have a hollow spherical morphology, possess γ-MnO2 structure and show high catalytic activity for the complete four-electron reaction pathway of the oxygen reduction reaction (ORR) in alkaline electrolyte. Meanwhile, the catalysts synthesized via radiolytic reduction possess a rod-like morphology with a Mn3O4 bulk structure and favour the incomplete two-electron reaction pathway for ORR. The high catalytic activity of the manganese oxide synthesized via the oxidation route can be attributed to high electrochemical surface area and increased amount of Mn3+ on the surface as compared to those in the sample obtained via the reduction route.

Shortened telomere length in peripheral blood leukocytes of patients with lung cancer, chronic obstructive pulmonary disease in a high indoor air pollution region in China.

Lung cancer and chronic obstructive pulmonary disease (COPD) are closely linked diseases. In Xuanwei, China, the extremely high incidence and mortality rates of lung cancer and COPD are associated with exposure to household smoky coal burning. Previous studies found that telomere length was related to lung disease. The objective of this study is to investigate the relationship of peripheral blood leukocyte telomere length to both lung cancer and COPD, as well as indoor coal smoke exposure in Xuanwei. We measured telomere length using quantitative polymerase chain reaction (qPCR) in peripheral blood leukocytes of 216 lung cancer patients, 296 COPD patients, and 426 healthy controls from Xuanwei. The telomere length ratios (mean ± SD) in patients with lung cancer (0.76 ± 0.35) and COPD (0.81 ± 0.35) were significantly shorter than in that of controls (0.95 ± 0.39). Individuals with the shortest tertile telomere length had 3.90- and 4.54-fold increased risks of lung cancer and COPD, respectively, compared with individuals with the longest tertile telomere length. No correlation was found between telomere length and pack-years of smoking. In healthy subjects, coal smoke exposure level affected telomere length. Lung function was positively and negatively associated with telomere length and environmental exposure, respectively, when combination the control and COPD groups. The result suggests that shortened telomere length in peripheral blood leukocytes was associated with lung cancer and COPD and might be affected by coal smoke exposure level in Xuanwei. Whether variation in telomere length caused by environmental exposure has a role in lung cancer and COPD development and exacerbation needs further research.

Differentiation of Human Parthenogenetic Embryonic Stem Cells into Functional Hepatocyte-like Cells.

Stem cell and tissue engineering-based therapies for acute liver failure (ALF) have been limited by the lack of an optimal cell source. We aimed to determine the suitability of human parthenogenetic embryonic stem cells (hPESCs) for the development of strategies to treat ALF. We studied the ability of human parthenogenetic embryonic stem cells (hPESCs) with high whole-genome SNP homozygosity, which were obtained by natural activation during in vitro fertilization (IVF), to differentiate into functional hepatocyte-like cells in vitro by monolayer plane orientation. hPESCs were induced on a single-layer flat plate for 21 d in complete medium with the inducers activin A, FGF-4, BMP-2, HGF, OSM, DEX, and B27. Polygonal cell morphology and binuclear cells were observed after 21 d of induction by using an inverted microscope. RT-qPCR results showed that the levels of hepatocyte-specific genes such as AFP, ALB, HNF4a, CYP3A4, SLCO1B3, and ABCC2 significantly increased after induction. Immunocytochemical assay showed CK18 and Hepa expression in the induced cells. Indocyanine green (ICG) staining showed that the cells had the ability to absorb and metabolize dyes. Detection of marker proteins and urea in cell culture supernatants showed that the cells obtained after 21 d of induction had synthetic and secretory functions. The typical ultrastructure of liver cells was observed using TEM after 21 d of induction. The results indicate that naturally activated hPESCs can be induced to differentiate into hepatocellular cells by monolayer planar induction.

Designed DNA nanostructure grafted with erlotinib for non-small-cell lung cancer therapy.

Chemotherapy for non-small-cell lung cancer (NSCLC) treatment has been employed over the past 20 years. However, poor water-solubility, low bioavailability and less drug accumulation of chemotherapeutic drugs restrict its antitumor activities in clinic. DNA nanostructures are proposed as drug carriers due to their intrinsic biocompatibility and programmability. In this work, we demonstrate a novel DNA nanocarrier grafted with erlotinib as an effective drug delivery system (DDS) for anti-cancer treatment. Specifically, erlotinib (Er), a hydrophobic small molecule drug targeting the epidermal growth factor receptor (EGFR), is covalently conjugated with azide (N3) modified DNA strands and subsequently self-assembled on spatially programmable erlotinib-grafted 6 × 6 × 64 nt DNA nanostructures. Thus, Er was successfully grafted on DNA carriers and transformed into a hydrophilic formulation. The antitumor efficacy was evaluated both in vitro and in vivo, and enhanced cytotoxicity toward A549 cells and the marked inhibition of tumor growth for non-small-cell lung cancer (NSCLC) were observed.