Integrating In Silico and In Vitro Approaches to Identify Natural Peptides with Selective Cytotoxicity against Cancer Cells.

Anticancer peptides (ACPs) are bioactive compounds known for their selective cytotoxicity against tumor cells via various mechanisms. Recent studies have demonstrated that in silico machine learning methods are effective in predicting peptides with anticancer activity. In this study, we collected and analyzed over a thousand experimentally verified ACPs, specifically targeting peptides derived from natural sources. We developed a precise prediction model based on their sequence and structural features, and the model's evaluation results suggest its strong predictive ability for anticancer activity. To enhance reliability, we integrated the results of this model with those from other available methods. In total, we identified 176 potential ACPs, some of which were synthesized and further evaluated using the MTT colorimetric assay. All of these putative ACPs exhibited significant anticancer effects and selective cytotoxicity against specific tumor cells. In summary, we present a strategy for identifying and characterizing natural peptides with selective cytotoxicity against cancer cells, which could serve as novel therapeutic agents. Our prediction model can effectively screen new molecules for potential anticancer activity, and the results from in vitro experiments provide compelling evidence of the candidates' anticancer effects and selective cytotoxicity.

Hernandonine-mediated autophagic cell death in hepatocellular carcinoma: Interplay of p53 and YAP signaling pathways.

Hepatocellular carcinoma (HCC), the primary form of liver cancer, is the third leading cause of cancer-related death globally. Hernandonine is a natural alkaloid derived from Hernandia nymphaeifolia that has been shown to exert various biological functions. In a previous study, hernandonine was shown to suppress the proliferation of several solid tumor cell lines without affecting normal human cell lines. However, little is known about the effect of hernandonine on HCC. Therefore, this study aimed to investigate the effect and mechanism of hernandonine on HCC in relation to autophagy. We found that hernandonine inhibited HCC cell growth in vitro and in vivo. In addition, hernandonine elicited autophagic cell death and DNA damage in HCC cells. RNA-seq analysis revealed that hernandonine upregulated p53 and Hippo signaling pathway-related genes in HCC cells. Small RNA interference of p53 resulted in hernandonine-induced autophagic cell death attenuation. However, inhibition of YAP sensitized HCC cells to hernandonine by increasing the autophagy induction. This is the first study to illustrate the complex involvement of p53 and YAP in the hernandonine-induced autophagic cell death in human HCC cells. Our findings provide novel evidence for the potential of hernandonine as a therapeutic agent for HCC treatment.

Assessment of Narrow-Band Imaging Algorithm for Video Capsule Endoscopy Based on Decorrelated Color Space for Esophageal Cancer: Part II, Detection and Classification of Esophageal Cancer.

Esophageal carcinoma (EC) is a prominent contributor to cancer-related mortality since it lacks discernible features in its first phases. Multiple studies have shown that narrow-band imaging (NBI) has superior accuracy, sensitivity, and specificity in detecting EC compared to white light imaging (WLI). Thus, this study innovatively employs a color space linked to décor to transform WLIs into NBIs, offering a novel approach to enhance the detection capabilities of EC in its early stages. In this study a total of 3415 WLI along with the corresponding 3415 simulated NBI images were used for analysis combined with the YOLOv5 algorithm to train the WLI images and the NBI images individually showcasing the adaptability of advanced object detection techniques in the context of medical image analysis. The evaluation of the model's performance was based on the produced confusion matrix and five key metrics: precision, recall, specificity, accuracy, and F1-score of the trained model. The model underwent training to accurately identify three specific manifestations of EC, namely dysplasia, squamous cell carcinoma (SCC), and polyps demonstrates a nuanced and targeted analysis, addressing diverse aspects of EC pathology for a more comprehensive understanding. The NBI model effectively enhanced both its recall and accuracy rates in detecting dysplasia cancer, a pre-cancerous stage that might improve the overall five-year survival rate. Conversely, the SCC category decreased its accuracy and recall rate, although the NBI and WLI models performed similarly in recognizing the polyp. The NBI model demonstrated an accuracy of 0.60, 0.81, and 0.66 in the dysplasia, SCC, and polyp categories, respectively. Additionally, it attained a recall rate of 0.40, 0.73, and 0.76 in the same categories. The WLI model demonstrated an accuracy of 0.56, 0.99, and 0.65 in the dysplasia, SCC, and polyp categories, respectively. Additionally, it obtained a recall rate of 0.39, 0.86, and 0.78 in the same categories, respectively. The limited number of training photos is the reason for the suboptimal performance of the NBI model which can be improved by increasing the dataset.

iDVEIP: A computer-aided approach for the prediction of viral entry inhibitory peptides.

With the notable surge in therapeutic peptide development, various peptides have emerged as potential agents against virus-induced diseases. Viral entry inhibitory peptides (VEIPs), a subset of antiviral peptides (AVPs), offer a promising avenue as entry inhibitors (EIs) with distinct advantages over chemical counterparts. Despite this, a comprehensive analytical platform for characterizing these peptides and their effectiveness in blocking viral entry remains lacking. In this study, we introduce a groundbreaking in silico approach that leverages bioinformatics analysis and machine learning to characterize and identify novel VEIPs. Cross-validation results demonstrate the efficacy of a model combining sequence-based features in predicting VEIPs with high accuracy, validated through independent testing. Additionally, an EI type model has been developed to distinguish peptides specifically acting as Eis from AVPs with alternative activities. Notably, we present iDVEIP, a web-based tool accessible at http://mer.hc.mmh.org.tw/iDVEIP/, designed for automatic analysis and prediction of VEIPs. Emphasizing its capabilities, the tool facilitates comprehensive analyses of peptide characteristics, providing detailed amino acid composition data for each prediction. Furthermore, we showcase the tool's utility in identifying EIs against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).

Assessment of hyperspectral imaging and CycleGAN-simulated narrowband techniques to detect early esophageal cancer.

The clinical signs and symptoms of esophageal cancer (EC) are often not discernible until the intermediate or advanced phases. The detection of EC in advanced stages significantly decreases the survival rate to below 20%. This study conducts a comparative analysis of the efficacy of several imaging techniques, including white light image (WLI), narrowband imaging (NBI), cycle-consistent adversarial network simulated narrowband image (CNBI), and hyperspectral imaging simulated narrowband image (HNBI), in the early detection of esophageal cancer (EC). In conjunction with Kaohsiung Armed Forces General Hospital, a dataset consisting of 1000 EC pictures was used, including 500 images captured using WLI and 500 images captured using NBI. The CycleGAN model was used to generate the CNBI dataset. Additionally, a novel method for HSI imaging was created with the objective of generating HNBI pictures. The evaluation of the efficacy of these four picture types in early detection of EC was conducted using three indicators: CIEDE2000, entropy, and the structural similarity index measure (SSIM). Results of the CIEDE2000, entropy, and SSIM analyses suggest that using CycleGAN to generate CNBI images and HSI model for creating HNBI images is superior in detecting early esophageal cancer compared to the use of conventional WLI and NBI techniques.

Assessment of Narrow Band Imaging Algorithm for Video Capsule Endoscopy Based on Decorrelated Color Space for Esophageal Cancer.

Video capsule endoscopy (VCE) is increasingly used to decrease discomfort among patients owing to its small size. However, VCE has a major drawback of not having narrow band imaging (NBI) functionality. The current VCE has the traditional white light imaging (WLI) only, which has poor performance in the computer-aided detection (CAD) of different types of cancer compared to NBI. Specific cancers, such as esophageal cancer (EC), do not exhibit any early biomarkers, making their early detection difficult. In most cases, the symptoms are unnoticeable, and EC is diagnosed only in later stages, making its 5-year survival rate below 20% on average. NBI filters provide particular wavelengths that increase the contrast and enhance certain features of the mucosa, thereby enabling early identification of EC. However, VCE does not have a slot for NBI functionality because its size cannot be increased. Hence, NBI image conversion from WLI can presently only be achieved in post-processing. In this study, a complete arithmetic assessment of the decorrelated color space was conducted to generate NBI images from WLI images for VCE of the esophagus. Three parameters, structural similarity index metric (SSIM), entropy, and peak-signal-to-noise ratio (PSNR), were used to assess the simulated NBI images. Results show the good performance of the NBI image reproduction method with SSIM, entropy difference, and PSNR values of 93.215%, 4.360, and 28.064 dB, respectively.

Microbiome analysis of maternal and neonatal microbial communities associated with the different delivery modes based on 16S rRNA gene amplicon sequencing.

OBJECTIVE: With the rising number of cases of non-vaginal delivery worldwide, scientists have been concerned about the influence of the different delivery modes on maternal and neonatal microbiomes. Although the birth rate trend is decreasing rapidly in Taiwan, more than 30 percent of newborns are delivered by caesarean section every year. However, it remains unclear whether the different delivery modes could have a certain impact on the postpartum maternal microbiome and whether it affects the mother-to-newborn vertical transmission of bacteria at birth. MATERIALS AND METHODS: To address this, we recruited 30 mother-newborn pairs to participate in this study, including 23 pairs of vaginal delivery (VD) and seven pairs of caesarean section (CS). We here investigate the development of the maternal prenatal and postnatal microbiomes across multiple body habitats. Moreover, we also explore the early acquisition of neonatal gut microbiome through a vertical multi-body site microbiome analysis. RESULTS AND CONCLUSION: The results indicate that no matter the delivery mode, it only slightly affects the maternal microbiome in multiple body habitats from pregnancy to postpartum. On the other hand, about 95% of species in the meconium microbiome were derived from one of the maternal body habitats; notably, the infants born by caesarean section acquire bacterial communities resembling their mother's oral microbiome. Consequently, the delivery modes play a crucial role in the initial colonization of the neonatal gut microbiome, potentially impacting children's health and development.

Open-framework hybrid zinc/tin selenide as an ultrafast adsorbent for Cs+, Ba2+, Co2+, and Ni2.

Efficient adsorption of radioactive 137Cs+ and 60Co2+ and their decay products 137Ba2+ and 60Ni2+ bears significance for hazard elimination in case of nuclear emergency, which relies on the adsorption rate enhancement that takes advantages of compositional and structural optimization. Herein, we report a zinc-doped selenidostannate constructed from T2-supertetrahedral clusters, namely K3.4(CH3NH3)0.45(NH4)0.15Zn2Sn3Se10·3.4 H2O (ZnSnSe-1K). The soft Se and micro-porosity synergistically endow this material with a binding affinity to Cs+, Ba2+, Co2+, and Ni2+ ions and ultrafast kinetics with R > 97.6% in 2-60 min. In particular, ZnSnSe-1K can remove 99.34% of Cs+ in 2 min (KdCs > 1.5 × 105 mL g-1), contributing to a record rate constant k2 of 9.240 g mg-1 min-1 that surpasses all metal chalcogenide adsorbents. ZnSnSe-1K exhibits good acid/base tolerance (pH = 0-12), and the adsorption capacities at neutral are 253.61 ± 9.15, 108.94 ± 25.32, 45.76 ± 14.19 and 38.49 ± 2.99 mg g-1 for Cs+, Ba2+, Co2+, and Ni2+, respectively. The adsorption performances resist well co-existing cations and anions, and the removal rates can keep above or close to 90% even in sea water. ZnSnSe-1K is employed in continuous column and membrane filtration, both of which shows excellent elimination efficiency (R > 99%) for mixed Cs+, Ba2+, Co2+, and Ni2+. Especially, the membrane with an ultrathin (70 µm) ZnSnSe-1K layer can remove 97-100% Cs+ in suction filtration with a short contact time of 0.33 s. Combined with the simple synthesis, facile elution and great irradiation resistance, ZnSnSe-1K emerges as a selenide adsorbent candidate for use in environmental remediation especially that involving nuclear waste disposal.

Efficient methods for multiple types of precise gene-editing in Chlamydomonas.

Precise gene-editing using CRISPR/Cas9 technology remains a long-standing challenge, especially for genes with low expression and no selectable phenotypes in Chlamydomonas reinhardtii, a classic model for photosynthesis and cilia research. Here, we developed a multi-type and precise genetic manipulation method in which a DNA break was generated by Cas9 nuclease and the repair was mediated using a homologous DNA template. The efficacy of this method was demonstrated for several types of gene editing, including inactivation of two low-expression genes (CrTET1 and CrKU80), the introduction of a FLAG-HA epitope tag into VIPP1, IFT46, CrTET1 and CrKU80 genes, and placing a YFP tag into VIPP1 and IFT46 for live-cell imaging. We also successfully performed a single amino acid substitution for the FLA3, FLA10 and FTSY genes, and documented the attainment of the anticipated phenotypes. Lastly, we demonstrated that precise fragment deletion from the 3'-UTR of MAA7 and VIPP1 resulted in a stable knock-down effect. Overall, our study has established efficient methods for multiple types of precise gene editing in Chlamydomonas, enabling substitution, insertion and deletion at the base resolution, thus improving the potential of this alga in both basic research and industrial applications.

Large area MoS2 thin film growth by direct sulfurization.

In this study, we present the growth of monolayer MoS2 (molybdenum disulfide) film. Mo (molybdenum) film was formed on a sapphire substrate through e-beam evaporation, and triangular MoS2 film was grown by direct sulfurization. First, the growth of MoS2 was observed under an optical microscope. The number of MoS2 layers was analyzed by Raman spectrum, atomic force microscope (AFM), and photoluminescence spectroscopy (PL) measurement. Different sapphire substrate regions have different growth conditions of MoS2. The growth of MoS2 is optimized by controlling the amount and location of precursors, adjusting the appropriate growing temperature and time, and establishing proper ventilation. Experimental results show the successful growth of a large-area single-layer MoS2 on a sapphire substrate through direct sulfurization under a suitable environment. The thickness of the MoS2 film determined by AFM measurement is about 0.73 nm. The peak difference between the Raman measurement shift of 386 and 405 cm-1 is 19.1 cm-1, and the peak of PL measurement is about 677 nm, which is converted into energy of 1.83 eV, which is the size of the direct energy gap of the MoS2 thin film. The results verify the distribution of the number of grown layers. Based on the observation of the optical microscope (OM) images, MoS2 continuously grows from a single layer of discretely distributed triangular single-crystal grains into a single-layer large-area MoS2 film. This work provides a reference for growing MoS2 in a large area. We expect to apply this structure to various heterojunctions, sensors, solar cells, and thin-film transistors.

Prospects of microalgae in nutraceuticals production with nanotechnology applications.

Nutraceutical supplements provide health benefits, such as fulfilling the lack of nutrients in the human body or being utilized to treat or cure certain diseases. As the world population is growing, certain countries are experiencing food crisis challenges, causing natural foods are not sustainable to be used for nutraceutical production because it will require large-scale of food supply to produce enriched nutraceutics. The high demand for abundant nutritional compounds has made microalgae a reliable source as they can synthesize high-value molecules through photosynthetic activities. However, some microalgae species are limited in growth and unable to accumulate a significant amount of biomass due to several factors related to environmental conditions. Therefore, adding nanoparticles (NPs) as a photocatalyst is considered to enhance the yield rate of microalgae in an energy-saving and economical way. This review focuses on the composition of microalgal biomass for nutraceutical production, the health perspectives of nutritional compounds on humans, and the application of nanotechnology on microalgae for improved production and harvesting. The results obtained show that microalgal-based compounds indeed have better nutrients content than natural foods. However, nanotechnology must be further comprehended to make them non-hazardous and sustainable.

A flexible liposomal polymer complex as a platform of specific and regulable immune regulation for individual cancer immunotherapy.

BACKGROUND: The applicability and therapeutic efficacy of specific personalized immunotherapy for cancer patients is limited by the genetic diversity of the host or the tumor. Side-effects such as immune-related adverse events (IRAEs) derived from the administration of immunotherapy have also been observed. Therefore, regulatory immunotherapy is required for cancer patients and should be developed. METHODS: The cationic lipo-PEG-PEI complex (LPPC) can stably and irreplaceably adsorb various proteins on its surface without covalent linkage, and the bound proteins maintain their original functions. In this study, LPPC was developed as an immunoregulatory platform for personalized immunotherapy for tumors to address the barriers related to the heterogenetic characteristics of MHC molecules or tumor associated antigens (TAAs) in the patient population. Here, the immune-suppressive and highly metastatic melanoma, B16F10 cells were used to examine the effects of this platform. Adsorption of anti-CD3 antibodies, HLA-A2/peptide, or dendritic cells' membrane proteins (MP) could flexibly provide pan-T-cell responses, specific Th1 responses, or specific Th1 and Th2 responses, depending on the host needs. Furthermore, with regulatory antibodies, the immuno-LPPC complex properly mediated immune responses by adsorbing positive or negative antibodies, such as anti-CD28 or anti-CTLA4 antibodies. RESULTS: The results clearly showed that treatment with LPPC/MP/CD28 complexes activated specific Th1 and Th2 responses, including cytokine release, CTL and prevented T-cell apoptosis. Moreover, LPPC/MP/CD28 complexes could eliminate metastatic B16F10 melanoma cells in the lung more efficiently than LPPC/MP. Interestingly, the melanoma resistance of mice treated with LPPC/MP/CD28 complexes would be reversed to susceptible after administration with LPPC/MP/CTLA4 complexes. NGS data revealed that LPPC/MP/CD28 complexes could enhance the gene expression of cytokine and chemokine pathways to strengthen immune activation than LPPC/MP, and that LPPC/MP/CTLA4 could abolish the LPPC/MP complex-mediated gene expression back to un-treatment. CONCLUSIONS: Overall, we proved a convenient and flexible immunotherapy platform for developing personalized cancer therapy.

In Vivo Automatic and Quantitative Measurement of Adult Human Larynx and Vocal Fold Images.

INTRODUCTION: Qualitative laryngoscopy belongs to a diagnostic routine. Nevertheless, quantitative morphometric measurements of laryngeal structures remain challenging. This study aimed to introduce a special laser projection device that can facilitate computer-assisted digitalized analysis and provide important quantitative information for diagnostics and treatment planning. MATERIALS AND METHODS: The laryngeal images were captured with our device, which contained two parallel laser beams in order to provide the scaling reference. The maximum length of the vocal fold during respiration and vibration (phonation), vocal width at midpoint, total fold area, maximum cross-sectional area of the glottic space, and maximum vocal fold angle were determined and calculated. These parameters were analyzed and compared on the basis of age, sex, body height, body weight and body mass index. RESULTS: A total of 87 subjects were enrolled in this study, comprising 39 males and 48 females. The age range for all subjects was 21 to 80 years old. The maximum value of the glottic area and vocal angle showed no significant gender difference. Both the respiration and vibration vocal fold length was significantly longer in males than in females. The vocal width revealed no gender difference, but the fold area during both respiration and phonation was significantly larger in men than in women. As for the respiration-to-vibration ratio of the vocal length, there was a trend, but without statistical significance (P = 0.06), toward a higher length compression ratio in men than in women. Meanwhile, age was found to have a strong relationship with vocal width during phonation. The width of vibration vocal fold decreased with aging significantly. CONCLUSION: Our innovative module can provide reference parameters, which makes it possible to directly estimate the objective absolute values of relevant laryngeal structures. Our non-invasive approach can be used during routine laryngoscopy and the findings easily documented. In future, we can extend its clinical application to measure subtle laryngeal or hypopharyngeal changes, which are difficult to objectively quantify.

Transdermal nanolipoplex simultaneously inhibits subcutaneous melanoma growth and suppresses systemically metastatic melanoma by activating host immunity.

Benefit for clinical melanoma treatments, the transdermal neoadjuvant therapy could reduce surgery region and increase immunotherapy efficacy. Using lipoplex (Lipo-PEG-PEI-complex, LPPC) encapsulated doxorubicin (DOX) and carrying CpG oligodeoxynucleotide; the transdermally administered nano-liposomal drug complex (LPPC-DOX-CpG) would have high cytotoxicity and immunostimulatory activity to suppress systemic metastasis of melanoma. LPPC-DOX-CpG dramatically suppressed subcutaneous melanoma growth by inducing tumor cell apoptosis and recruiting immune cells into the tumor area. Animal studies further showed that the colonization and growth of spontaneously metastatic melanoma cells in the liver and lung were suppressed by transdermal LPPC-DOX-CpG. Furthermore, NGS analysis revealed IFN-γ and NF-κB pathways were triggered to recruit and activate the antigen-presenting-cells and effecter cells, which could activate the anti-tumor responses as the major mechanism responsible for the therapeutic effect of LPPC-DOX-CpG. Finally, we have successfully proved transdermal LPPC-DOX-CpG as a promising penetrative carrier to activate systemic anti-tumor immunity against subcutaneous and metastatic tumor.

Diagnosis and treatment of malignant mesothelioma of the tunica vaginalis testis: a series of 7 cases / 中华外科杂志

Objective: To investigate the clinical features, diagnosis, prognosis of malignant mesothelioma of the tunica vaginalis testis (MMTVT). Methods: The clinicopathological data of 7 patients with MMTVT who treated at Sun Yat-sen University Cancer Center between January 2010 and October 2022 were retrospectively reviewed. Cases were first diagnosed at (M (IQR)) 49 (23) years old (range: 27 to 64 years old). The main clinical manifestations were scrotal enlargement (7 cases) and hydrocele (2 cases). Results: Three patients underwent radical orchiectomy as initial treatment, 2 cases underwent hydrocelectomy due to diagnosis of hydrocele, followed by radical orchiectomy at Sun Yat-sen University Cancer Center, and 2 cases underwent transscrotal orchiectomy. Common tumor markers of testicular cancer were not significantly elevated in MMTVT. The expression of tumor PD-L1 was positive in 2 out of the 3 cases. One patient received adjuvant chemotherapy and 2 patients received first-line chemotherapy after tumor recurrence. Chemotherapy regimens used include cisplatin+pemetrexed. Up to October 2022, 3 cases relapsed, of which 2 cases died. The median overall survival was 35 months (range: 4 to 87 months) and the median progression-free survival was 6 months (range: 2 to 87 months). Conclusions: MMTVT at early stage should be treated with early radical orchiectomy and followed up closely after surgery. The cisplatin+pemetrexed regimen is a common option for the treatment of metastatic MMTVT, while whether immune checkpoint inhibitors could serve as a second-line treatment option deserves further research.

Efficacy and safety of anlotinib monotherapy and combinated therapy in the treatment of advanced pheo-chromocytoma/paraganglioma / 实用医学杂志

Objective To evaluate the efficacy and safety of anlotinib monotherapy and combined therapy in patients with advanced pheochromocytoma/paraganglioma.Methods Nine patients with advanced pheochromo-cytoma/paraganglioma(PPGL)who were admitted to the Department of Urology,Sun Yat-sen University Cancer Center from January 2018 to June 2023 were collected.Patients were divided into four groups according to different treatments:anlotinib monotherapy group(3 patients),anlotinib combined with PD-1 monoclonal antibody immuno-therapy group(3 patients),anlotinib combined with immunotherapy and chemotherapy group(2 patients),and anlotinib combined with chemotherapy group(1 patients).The effectiveness and safety of different treatment regiments of anlotinib were analyzed.Results Objective response rate(ORR):(44%),Partial response(PR):(44%),Stable disease(SD):(44%),Progressive disease(PD):(11%),Disease control rate(DCR):(89%).The ORR of 2 patients with SDH gene mutation,SDHB and SDHD respectively,was 100%.Median overall survival time(OS)was 16.3 months(IQR:11.3～21.8 months).Median progression-free survival(PFS)was 16.3 months(IQR:9.8～20.8 months).There were 2 patients with adverse events grade≥3/4,all of which were hypertension.Conclusions Anlotinib monotherapy and combined therapy have preliminary efficacy and manageable safety in the treatment of advanced pheochromocytoma/paraganglioma.

Assessment and application of tumor regression grade after neoadjuvant chemotherapy in bladder cancer / 中华泌尿外科杂志

Objective:To verify the prognostic significance of the tumor regression grade (TRG) for muscle-invasive bladder cancer (MIBC) patients undergoing radical cystectomy (RC) after neoadjuvant chemotherapy.Methods:The data of 70 MIBC patients treated with gemcitabine combined with cisplatin neoadjuvant chemotherapy and RC in Sun Yat-sen University Cancer Center between July 2016 to November 2021 were retrospectively reviewed. There were 65 males and 5 females, with an average age(59.79±10.56)years old. The patients accepted transurethral resection of bladder tumor (TURBT) specimens before neoadjuvant chemotherapy. Clinicopathological characteristics of patients were recorded and TRG was assessed. TRG evaluation criteria: TRG 1 was defined as no cancer residue, TRG 2 was defined as the proportion of residual cancer area to tumor bed area <50%, and TRG 3 was defined as the proportion of residual cancer area to the area of the tumor bed ≥ 50%. Chi-square test or Fisher's exact test were used to compare the relationship between patients' clinicopathological characteristics and TRG. The relationship between post-neoadjuvant therapy tumor and node(ypTN)stage, and survival, including overall survival(OS)and recurrence-free survival (RFS) were analyzed by Kaplan-Meier analysis. The pathologically locally descending disease was defined as (ypT < T 2 and ypN=N 0) and pathologically locally advanced disease was defined as (ypT≥T 2 and/or ypN ≥N 1). Cox regression was used for univariate and multivariate analysis of OS and RFS. Results:Chi-square test or Fisher exact test analysis showed TRG was significantly associated with ypT stage ( P < 0.001), ypN stage ( P = 0.002), lympho-vascular invasion ( P<0.001) and variant histology ( P<0.001). The OS of patients with TRG 1, TRG 2 and TRG 3 were 20.5(10.3, 31.8), 17.0(11.0, 30.8)and 15.0(11.0, 26.0) months, respectively, and the difference was significantly different( P = 0.037). The RFS of patients with TRG 1, TRG 2 and TRG 3 were 15.0(8.3, 25.5), 15.0(8.0, 27.0)and 11.0(4.5, 25.5) months, respectively, and the difference was significantly different ( P=0.029). There were significant differences between patients with pathologically locally descending disease and locally advanced disease in OS [18.5(10.3, 30.8)vs.15.0(11.0, 27.3)months, P = 0.013] and RFS [14.0(8.0, 24.0)vs. 11.5(8.0, 26.8)months, P = 0.012]. Among patients with locally advanced pathology, the OS was 19.5(11.0, 32.5)months for patients with TRG ≤2, 13.5(10.8, 26.0)months for patients with TRG 3( P=0.140). The RFS was 12.0(8.0, 31.0)months for those patients with TRG ≤2 and 11.0(6.0, 26.0)months for those patients with TRG 3( P = 0.180). Cox univariate analyses showed that patients with TRG 3 were associated with decreased OS ( HR = 6.043, 95% CI 1.170-31.213, P = 0.032) and RFS ( HR = 6.354, 95% CI 1.231-31.802, P = 0.027). Conclusions:This study showed that TRG was correlated with OS and RFS among patients. The patients who had the higher TRG had the worse prognosis. It was confirmed that TRG predicted the prognosis of patients undergoing radical cystectomy after neoadjuvant chemotherapy. Therefore, TRG assessment is recommend in pathology report for patients who had radical cystectomy after neoadjuvant chemotherapy.

Anticancer peptide Q7 suppresses the growth and migration of human endometrial cancer by inhibiting DHCR24 expression and modulating the AKT-mediated pathway.

Endometrial cancer is one of the most common malignancy affecting women in developed countries. Resection uterus or lesion area is usually the first option for a simple and efficient therapy. Therefore, it is necessary to find a new therapeutic drug to reduce surgery areas to preserve fertility. Anticancer peptides (ACP) are bioactive amino acids with lower toxicity and higher specificity than chemical drugs. This study is to address an ACP, herein named Q7, which could downregulate 24-Dehydrocholesterol Reductase (DHCR24) to disrupt lipid rafts formation, and sequentially affect the AKT signal pathway of HEC-1-A cells to suppress their tumorigenicity such as proliferation and migration. Moreover, lipo-PEI-PEG-complex (LPPC) was used to enhance Q7 anticancer activity in vitro and efficiently show its effects on HEC-1-A cells. Furthermore, LPPC-Q7 exhibited a synergistic effect in combination with doxorubicin or paclitaxel. To summarize, Q7 was firstly proved to exhibit an anticancer effect on endometrial cancer cells and combined with LPPC efficiently improved the cytotoxicity of Q7.

Involvement of AMPKα and MAPK-ERK/-JNK Signals in Docetaxel-Induced Human Tongue Squamous Cell Carcinoma Cell Apoptosis.

Cancers of the oral cavity can develop in the anatomic area extending from the lip, gum, tongue, mouth, and to the palate. Histologically, about 85-90% of oral cavity cancers are of the type squamous cells carcinomas (SCCs). The incidence of oral tongue SCC is higher in the tongue than any other anatomic area of the oral cavity. Here, we investigated the therapeutic effects and molecular mechanisms of docetaxel, which is a paclitaxel antitumor agent, on the cell growth of a human tongue SCC-derived SAS cell line. The results showed that docetaxel (10-300 nM) induced cytotoxicity and caspase-3 activity in SAS cells. Moreover, docetaxel (100 nM) promoted the expression of apoptosis-related signaling molecules, including the cleavages of caspase-3, caspase-7, and poly (ADP-ribose) polymerase (PARP). In mitochondria, docetaxel (100 nM) decreased the mitochondrial membrane potential (MMP) and Bcl-2 mRNA and protein expression and increased cytosolic cytochrome c protein expression and Bax mRNA and protein expression. In terms of mitogen-activated protein kinase (MAPK) and adenosine monophosphate-activated protein kinase (AMPK) signaling, docetaxel increased the expression of phosphorylated (p)-extracellular signal-regulated kinase (ERK), p-c-Jun N-terminal kinase (JNK), and p-AMPKα protein expression but not p-p38 protein expression. Moreover, the increase in caspase-3/-7 activity and Bax protein expression and decreased Bcl-2 protein expression and MMP depolarization observed in docetaxel-treated SAS cells could be reversed by treatment with either SP600125 (a JNK inhibitor), PD98059 (an MEK1/2 (mitogen-activated protein kinase kinase 1/2) inhibitor), or compound c (an AMPK inhibitor). The docetaxel-induced increases in p-JNK, p-ERK, and p-AMPKα protein expression could also be reversed by treatment with either SP600125, PD98059, or compound c. These results indicate that docetaxel induces human tongue SCC cell apoptosis via interdependent MAPK-JNK, MAPK-ERK1/2, and AMPKα signaling pathways. Our results show that docetaxel could possibly exert a potent pharmacological effect on human oral tongue SCC cell growth.

M-Sn-Q (M = Zn, Cd; Q = S, Se) Compounds Templated by (Alkyl)ammonium Species: Synthesis, Crystal Structure, and Sr2+ Adsorption Property.

Deep investigations on the synthetic and structural chemistry of heterometallic chalcogenidostannates bear fundamental significance for the establishment of the structure-property relationship that would offer guidance on the functional material innovation. Presented here are four ammonium- and/or alkylammonium-directed M-Sn-Q (M = Zn, Cd; Q = S, Se) compounds, namely, [NH4]7[H3O]3Zn4Sn4S17 (1), [NH4]5[(CH3)2NH2]Zn4Sn5S17 (2), [CH3CH2NH3]22Zn16Sn12Se51(H2O)4·16H2O (3), and [NH4]2CdSnSe4 (4). All four compounds were synthesized in deep eutectic solvents (DESs) or ethylamine aqueous solution, both of which function simultaneously as reaction media and structure-directing agents. Compound 1 consists of discrete P1-[Zn4Sn4S17]10- clusters templated by mixed [NH4]+/[H3O]+ cations. In compound 2, such P1 clusters are bridged by Sn4+ ions in a 4,4-connection mode to form a [Zn4Sn5S17]n6n- framework with three types of cavities (I-III) varying in size. The two smaller cavities (I and II) accommodate NH4+ while the larger one(III) is occupied by [(CH3)2NH2]+, reflecting the rational size-dependence of cations on cavities. Compound 3 features an [Zn16Sn12Se51(H2O)4]n22n- open framework constructed from the 4,3-connection of P1-[Zn4Sn4Se17]10- clusters and {Zn(H2O)}2+ bridges. This linkage mode contributes to a large cage-like subunit (inner dimension: 21.99 × 9.06 Å2) and therefore an ultrahigh porosity that are occupied by [CH3CH2NH3]+ cations and water molecules (volume fraction: 57.7%). Compound 4 exists as a stacking of [CdSnSe4]n2n- chains, which are composed of alternatively arranged {CdSe4} and {SnSe4} tetrahedra, in combination with [NH4]+ cations as both charge-compensating and space-filling agents. Detailed synthetic, structural, and topological analyses were performed on these solid materials, coupled with extensive investigations on their optical and thermal properties. Compound 3 exhibits an efficient Sr2+ adsorption performance, featuring ultrafast kinetics (94.69% in 5 min), high removal rate (98.57% in 20 min) at equilibrium, and high capacity (104.17 ± 23.53 mg g-1).