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Natural exosomes can express specific proteins and carbohydrate molecules on the surface and hence have demonstrated the great potentials for gene therapy of cancer. However, the use of natural exosomes is restricted by their low transfection efficiency. Here, we report a novel targeting tLyp-1 exosome by gene recombinant engineering for delivery of siRNA to cancer and cancer stem cells. To reach such a purpose, the engineered tLyp-1-lamp2b plasmids were constructed and amplified in Escherichia coli. The tLyp-1-lamp2b plasmids were further used to transfect HEK293T tool cells and the targeting tLyp-1 exosomes were isolated from secretion of the transfected HEK293T cells. Afterwards, the artificially synthesized siRNA was encapsulated into targeting tLyp-1 exosomes by electroporation technology. Finally, the targeting siRNA tLyp-1 exosomes were used to transfect cancer or cancer stem cells. Results showed that the engineered targeting tLyp-1 exosomes had a nanosized structure (approximately 100 nm) and high transfection efficiency into lung cancer and cancer stem cells. The function verifications demonstrated that the targeting siRNA tLyp-1 exosomes were able to knock-down the target gene of cancer cells and to reduce the stemness of cancer stem cells. In conclusion, the targeting tLyp-1 exosomes are successfully engineered, and can be used for gene therapy with a high transfection efficiency. Therefore, the engineered targeting tLyp-1 exosomes offer a promising gene delivery platform for future cancer therapy., Graphical abstract The tLyp-1-lamp2b plasmid transfected HEK293T cells can secreted tumor targeting tLyp-1 exosomes. By electroporation technology, targeting tLyp-1 exosomes were loaded with siRNA. When targeting tLyp-1 exosome ruptured in cytoplasm, siRNA was loaded into the RNA-induced silencing complex (RISC). The sense (passenger) strand was degraded while the antisense (guide) strand directs RISC to mRNA that has a complementary sequence, thereby resulting in the silence of target gene.Image, graphical abstract

Though a number of on-off or off-on fluorescent probes have been developed for the detection of thiophenol by using its unique recognition groups, such as 2, 4-dinitrophenyl ether, 2, 4-dinitrophenyl sulfonamide, and 2, 4-dinitrophenyl sulfonate, up to now, there are few probes that can detect thiophenol by the proportional fluorescence signal. We developed a ratiometric fluorescent probe with coumarin pyridine derivative as fluorophore and 2, 4-dinitrophenyl ether moiety as the sensing unit which could be used to detect thiophenol derivatives by the aromatic nucleophilic substitution reaction. This probe (CPBPN) displayed significant change in fluorescence ratio (256 fold) to result in a more reliable analysis by self-calibration and a relatively low detection limit of 24 nM toward 4-methylthiophenol (MTP) within 30 min to achieve more sensitivity. Besides, the probe was also applied to detect the presence of thiophenol derivatives in actual water samples and fluorescence imaging in living cells. The present work is of great importance for monitoring environmental pollutants and studying their biological function.

Triple negative breast cancer (TNBC) has been characterized as a very heterogeneous subtype, and is more invasive and non-expressing of the genes for the estrogen receptor (ER), progesterone receptor (PR) and HER2/neu, with poor prognosis, and hence the efficacy of regular chemotherapy is very limited. Here, we report a kind of double strand RNA (dsRNA) mPEI nanoparticle for treatment of invasive TNBC. The studies were performed on TNBC cells in vitro and in TNBC cancer-bearing mice. The results showed that dsRNA mPEI nanoparticles were able to effectively transfect cells, and demonstrated a strong capability in knocking-down the Fra-1 gene and down-stream MMP-1 and MMP-9 genes in TNBC cells and TNBC cancer-bearing mice, thereby inhibiting the invasion and migration of cells. After intratumoral injection, dsRNA mPEI nanoparticles exhibited a robust anticancer efficacy in TNBC cancer-bearing mice, and the anticancer efficacy was superior to that of paclitaxel. In conclusion, dsRNA mPEI nanoparticles are able to effectively treat aggressive TNBC, and the mechanism studies reveal that they take effect by knocking-down Fra-1 relevant genes, hence interfering in transcription and translation of the genes, which are necessary for growth and metastasis of TNBC. Therefore, the present study offers a new and promising formulation and strategy for effective treatment of TNBC.

This work presented a benzothiazole-based fluorescent probe for the detection of benzenethiol derivatives using 2, 4-dinitrobenzene moiety as a sensing unit. This probe (NCABT) was able to instantaneously respond to 4-methylbenzenethiol (MTP) within 5 min. In detecting MTP, this probe displayed a low limit of detection (49 nM). Furthermore, the probe has been proved to have the potential to detect benzenethiol derivatives with electron-donating group in real water samples.

The analog frontend (AFE) coupling circuit is a crucial processing element for data acquisition systems based on analog-to-digital converters (ADCs). Currently, high-speed and high-resolution ADCs are predominantly designed with differential input stages. Conventional high-speed ADC drivers are mainly AC-coupled by employing transformers (Baluns) or fully differential amplifiers (FDAs) with blocking capacitors. However, the results of this study indicate that a certain degree of DC offset error exists and manifests itself as the baseline error in the presence of power dividers connecting several DC-coupled channels that implement high-dynamic-range (HDR) signal conditioning. The study involves a theoretical analysis and explanation of the baseline offset error. The offset error can potentially lead to unexpected out-of-range issues for sampling devices, including high-speed ADCs and switched capacitor array ASICs. High-performance FDAs are adopted, and an offset-free DC-coupled AFE circuit is proposed to address the aforementioned issue using two-stage amplification and a resistive attenuator. The proposed methodology is verified via circuit simulations and hardware design. Thus, the baseline offset problem can be accurately solved using the proposed circuit by minimizing the neglectable error. The proposed circuit facilitates improvements in the high-precision measurement of HDR signals in many nuclear physics experiments and some applications in the DC-coupling scheme with FDAs involving resistive power dividers.

The decline of male fertility and its consequences on human populations are important public-health issues. However, there are limited choices for treatment of male infertility. In an attempt to identify a compound that could promote male fertility, we identified and characterized a library of small molecules from an ancient formulation Wuzi Yanzong-Pill, which was used as a folk medicine since the Tang dynasty of China. We found that SB enabled evident repairs in oligoasthenospermia-associated testicular tissue abnormality and in spermatogenesis disruption, resulting in significant improvements of sperm count, mobility, and reproductive ability in oligoasthenospermia mice. Furthermore, SB could alter substantial testicular genes (2033), among which, upregulation of Fst while downregulation of Inhba involved in reproductive signaling pathway could explain its role in enhancing spermatogenesis. The encouraging preclinical data with pharmacokinetics warranted a rapid development of this new class of therapeutic agent. Our finding provides a strong potent drug for treatment of male infertility.

Tissue regeneration, such as pancreatic islet tissue propagation in vitro, could serve as a promising strategy for diabetes therapy and personalized drug testing. However, such a protocol has not been realized yet. Propagation could be divided by two steps, which are: (1) expansion in vitro and (2) repeat passaging. Even the in vitro expansion of the islet has not been achieved to date. Here, we describe a method to enable the expansion of islet clusters isolated from pregnant mice or wild-type rats by employing a combination of specific regeneration factors and chemical compounds in vitro. The expanded islet clusters expressed insulin, glucagon and somatostatin, which are markers corresponding to pancreatic β cells, α cells and δ cells, respectively. These different types of cells grouped together, were spatially organized and functioned similarly to primary islets. Further mechanistic analysis revealed that forskolin in our recipe contributed to renewal and regeneration, whereas exendin4 was essential for preserving islet cell identity. Our results provide a novel method for the in vitro expansion of islet clusters, which is an important step forward in developing future protocols and medium used for islet tissue propagation in vitro. Such method is important for future regenerative diabetes therapies and personalized medicine using large amounts of pancreatic islets derived from the same person.

Tissue regeneration, such as pancreatic islet tissue propagation in vitro, could serve as a promising strategy for diabetes therapy and personalised drug testing. However, such a strategy has not been realised yet. Propagation could be divided into two steps, in vitro expansion and repeated passaging. Even the first step of the in vitro islet expansion has not been achieved to date. Here, we describe a method that enables the expansion of islet clusters isolated from pregnant mice or wild-type rats by employing a combination of specific regeneration factors and chemical compounds in vitro. The expanded islet clusters expressed insulin, glucagon and somatostatin, which are markers corresponding to pancreatic β cells, α cells and δ cells, respectively. These different types of cells grouped together, were spatially organised and functioned similarly to primary islets. Further mechanistic analysis revealed that forskolin in our recipe contributed to renewal and regeneration, whereas exendin-4 was essential for preserving islet cell identity. Our results provide a novel method for the in vitro expansion of islet clusters, which is an important step forward in developing future protocols and media used for islet tissue propagation in vitro. Such method is important for future regenerative diabetes therapies and personalised medicines using large amounts of pancreatic islets derived from the same person.

In this paper, we present an ultrafast digitizer utilizing the DRS4 switched capacitor array application-specific integrated circuit to achieve an ultrafast sampling speed of at most 5 GS/s. We cascaded all eight channels (sub-channels) of a single DRS4 chip for increased storage depth. The digitizer contains four DRS4 chips, a quad-channel analog-to-digital converter, a controlling field-programmable gate array, a PXI interface, and an SFP+ connector. Consequently, each DRS4 channel has a depth of 8192 points and a vertical resolution of 14 bits. The readout sequences should be broken into several segments and then reordered to obtain the correct sequential data sets, and this offline procedure varies in different readout modes. This paper describes the design and implementation of the hardware; in particular, the respective processing procedures are described in detail. Furthermore, the offset error is calibrated and corrected to improve the precision of the captured waveform in both single-channel and high-resolution modes.

Antigen peptides and adjuvants have been extensively investigated for cancer immunotherapy, and they are expected to elicit specific immune responses for cancer treatment. However, the anti-cancer efficacy of antigen peptide and adjuvant-based cancer vaccines has been limited due to the inefficient delivery to draining lymph nodes after administration. Therefore, it is necessary to develop a suitable delivery system to transport antigen peptides and adjuvants. Here, we report a novel type of nanostructured lipovaccines for the treatment of melanoma by delivering antigen peptide (SL9) and oligodeoxynucleotide adjuvant (CpG) to the lymphatic vessels and to the draining lymph node. The SL9-CpG lipovaccines were characterized using dynamic laser scattering (DLS) and transmission electron microscopy (TEM). The lymph uptake, immune response elicitation and treatment effects were evaluated on melanoma-bearing C57BL/6 mice using flow cytometry (FCM), enzyme-linked immunosorbent assay (ELISA) and tumor inhibitory efficacy. The SL9-CpG lipovaccines were uniform with a nanoscale size (~70 nm), had high encapsulation efficiency, and exhibited effective lymph uptake, resulting in activation of specific cytotoxic CD8+ T cells, and release of IFN-&gamma, and a robust inhibition of tumor growth. Therefore, the nanostructured SL9-CpG lipovaccines offer a promising strategy for melanoma treatment.

Breast cancer is the most common malignant disease in women all over the world and its chemotherapy outcome is restricted by multidrug resistance. Here, a nanostructure by functional larotaxel liposomes decorated with guanine-rich quadruplex nucleotide-lipid derivative for treatment of resistant breast cancer is developed. The studies are performed on the resistant breast cancer cells and the cancer-bearing mice. The nucleotide-lipid derivative (DSPE-PEG2000 -C6 -GT28nt) is synthesized by introducing a hydrophobic hexyl linkage between GT-28nt (containing 17 guanines and 11 thymidines) and DSPE-PEG2000 -NHS, and is incorporated on the functional larotaxel liposomes for specific binding with nucleolin receptor on the resistant cancer cells. The studies demonstrate that the liposomes had long circulatory effect, targeted capability, and significant anticancer efficacy in resistant cancer-bearing mice. The studies further reveal their action mechanism, consisting of blocking depolymerization of microtubules, arresting cell cycle, blocking JAK-STAT signaling pathway, and inhibiting activity of antiapoptotic proteins. In conclusion, the functional larotaxel liposomes can be used for effective treatment of drug-resistant breast cancer, and this study also offers a novel targeted nanomedicine based on nucleotide-lipid derivative.

A metal-free iodine-catalyzed intramolecular amination has been developed for the practical synthesis of pyrrolo[2,3-b]indoles from readily available tryptophan esters. The transformation has been applied to a wide array of substrates and can be performed on gram scale under very mild conditions.

Background: This study aims to evaluate the short-term efficacy of concurrent chemoradiotherapy (CCRT) in primary fallopian tube carcinoma (PFTC) using magnetic resonance diffusion-weighted imaging (MR-DWI). Patients and Methods: Total abdominal irradiation was performed for 61 PFTC patients after surgery, and paclitaxel and carboplatin were used for CCRT. According to the response evaluation criteria in solid tumors (RECIST1.1), patients were divided into a sensitive (n = 36) and a resistant group (n = 25). Pearson correlation analysis was conducted to assess the correlations of tumor regression rate with apparent diffusion coefficient (ADC)pre, ADCpost, and ∆ADCpost. The efficacy of CCRT in PFTC using MR-DWI was evaluated by ROC curve, logistic regression analysis, Kaplan-Meier survival curve, and Cox regression model. Results: The ADCpre in both the sensitive and the resistant group was negatively associated with the tumor regression rate (r = -0.508), while the ADCpost (r = 0.454) and ∆ADCpost (r = 0.769) were positively associated with the tumor regression rate (all p < 0.05). Histopathological type, FIGO stage, lymphatic metastasis, tumor regression rate, ADCpre, ADCpost, and ∆ADCpost were confirmed as key factors for CCRT in PFTC (all p < 0.05). Conclusion: Our retrospective study demonstrates the predictive value of MR-DWI in CCRT for PFTC patients.