Antibody-drug conjugates in gastric cancer: from molecular landscape to clinical strategies.

Antibody-drug conjugates (ADCs) represent a crucial component of targeted therapies in gastric cancer, potentially altering traditional treatment paradigms. Many ADCs have entered rigorous clinical trials based on biological theories and preclinical experiments. Modality trials have also been conducted in combination with monoclonal antibody therapies, chemotherapies, immunotherapies, and other treatments to enhance the efficacy of drug coordination effects. However, ADCs exhibit limitations in treating gastric cancer, including resistance triggered by their structure or other factors. Ongoing intensive researches and preclinical experiments are yielding improvements, while enhancements in drug development processes and concomitant diagnostics during the therapeutic period actively boost ADC efficacy. The optimal treatment strategy for gastric cancer patients is continually evolving. This review summarizes the clinical progress of ADCs in treating gastric cancer, analyzes the mechanisms of ADC combination therapies, discusses resistance patterns, and offers a promising outlook for future applications in ADC drug development and companion diagnostics.

Dynein Light Intermediate Chains Exhibit Different Arginine Methylation Patterns.

BACKGROUND: The motor protein dynein is integral to retrograde transport along microtubules and interacts with numerous cargoes through the recruitment of cargo-specific adaptor proteins. This interaction is mediated by dynein light intermediate chain subunits LIC1 (DYNC1LI1) and LIC2 (DYNC1LI2), which govern the adaptor binding and are present in distinct dynein complexes with overlapping and unique functions. METHODS: Using bioinformatics, we analyzed the C-terminal domains (CTDs) of LIC1 and LIC2, revealing similar structural features but diverse post-translational modifications (PTMs). The methylation status of LIC2 and the proteins involved in this modification were examined through immunoprecipitation and immunoblotting analyses. The specific methylation sites on LIC2 were identified through a site-directed mutagenesis analysis, contributing to a deeper understanding of the regulatory mechanisms of the dynein complex. RESULTS: We found that LIC2 is specifically methylated at the arginine 397 residue, a reaction that is catalyzed by protein arginine methyltransferase 1 (PRMT1). CONCLUSIONS: The distinct PTMs of the LIC subunits offer a versatile mechanism for dynein to transport diverse cargoes efficiently. Understanding how these PTMs influence the functions of LIC2, and how they differ from LIC1, is crucial for elucidating the role of dynein-related transport pathways in a range of diseases. The discovery of the arginine 397 methylation site on LIC2 enhances our insight into the regulatory PTMs of dynein functions.

Deficiency of Macf1 in osterix expressing cells decreases bone formation by Bmp2/Smad/Runx2 pathway.

Microtubule actin cross-linking factor 1 (Macf1) is a spectraplakin family member known to regulate cytoskeletal dynamics, cell migration, neuronal growth and cell signal transduction. We previously demonstrated that knockdown of Macf1 inhibited the differentiation of MC3T3-E1 cell line. However, whether Macf1 could regulate bone formation in vivo is unclear. To study the function and mechanism of Macf1 in bone formation and osteogenic differentiation, we established osteoblast-specific Osterix (Osx) promoter-driven Macf1 conditional knockout mice (Macf1f/f Osx-Cre). The Macf1f/f Osx-Cre mice displayed delayed ossification and decreased bone mass. Morphological and mechanical studies showed deteriorated trabecular microarchitecture and impaired biomechanical strength of femur in Macf1f/f Osx-Cre mice. In addition, the differentiation of primary osteoblasts isolated from calvaria was inhibited in Macf1f/f Osx-Cre mice. Deficiency of Macf1 in primary osteoblasts inhibited the expression of osteogenic marker genes (Col1, Runx2 and Alp) and the number of mineralized nodules. Furthermore, deficiency of Macf1 attenuated Bmp2/Smad/Runx2 signalling in primary osteoblasts of Macf1f/f Osx-Cre mice. Together, these results indicated that Macf1 plays a significant role in bone formation and osteoblast differentiation by regulating Bmp2/Smad/Runx2 pathway, suggesting that Macf1 might be a therapeutic target for bone disease.

Structure-activity relationship of novel low-generation dendrimers for gene delivery.

Structure-activity relationship (SAR) studies are very critical to design ideal gene vectors for gene delivery. However, It is difficult to obtain SAR information of low-generation dendrimers due to the lack of easy structural modification ways. Here, we synthesized a novel family of rigid aromatic backbone-based low-generation polyamidoamine (PAMAM) dendrimers. According to the number of primary amines, they were divided into two types: four-amine-containing PAMAM (DL1-DL5) and eight-amine-containing PAMAM (DL6-DL10). Due to the introduction of a rigid aromatic backbone, the low-generation PAMAM could be modified easier by different hydrophobic aliphatic chains. Several assays were used to study the interactions of the PAMAM dendrimers with plasmid DNA, and the results revealed that they not only had good DNA binding ability but also could efficiently condense DNA into spherical-shaped nanoparticles with suitable sizes and zeta potentials. The SAR studies indicated that the gene-transfection efficiency of the synthesized materials depended on not only the structure of their hydrophobic chains but also the number of primary amines. It was found that four-amine-containing PAMAM prepared from oleylamine (DL5) gave the best transfection efficiency, which was 3 times higher than that of lipofectamine 2000 in HEK293 cells. The cellular uptake mechanism mediated by DL5 was further investigated, and the results indicated that DL5/DNA complexes entered the cells mainly via caveolae and clathrin-mediated endocytosis. In addition, these low-generation PAMAMs modified with a single hydrophobic tail showed lower toxicity than lipofectamine 2000 in MC3T3-E1, MG63, HeLa, and HEK293 cells. These results reveal that such a type of low-generation polyamidoamines might be promising non-viral gene vectors, and also give us clues for the design of safe and high-efficiency gene vectors.

Rap2B promotes migration and invasion of human suprarenal epithelioma.

The aim of our study was to elucidate the role of Rap2B in the development of human suprarenal epithelioma and to investigate the effect of Rap2B on suprarenal epithelioma cells migration and invasion. We use tissue microarray and immunohistochemistry to evaluate Rap2B staining in 75 suprarenal epithelioma tissues and 75 tumor-adjacent normal renal tissues. And the expression of Rap2B protein in human suprarenal epithelioma cells and tissues was detected by western blot simultaneously. The role of Rap2B in suprarenal epithelioma cells migration and invasion was detected by using wound healing assay, cell migration assay, and matrigel invasion assay. After that, we performed western blot analysis and gelatin zymography to detect MMP-2 protein expression and enzyme activity. Our research showed that Rap2B expression was increased in tumor tissues compared with tumor-adjacent normal renal tissues. But no correlation was found between Rap2B expression and clinicopathological parameters. In addition, we found that Rap2B promoted the cell migration and invasion abilities, and Rap2B increased MMP-2 expression and enzyme activity in suprarenal epithelioma cells. Our data indicated that Rap2B expression is significantly increased in human suprarenal epithelioma and Rap2B can promote the cell migration and invasion abilities, which may provide a new target for the treatment of suprarenal epithelioma.

Physiological effects of microgravity on bone cells.

Life on Earth developed under the influence of normal gravity (1g). With evidence from previous studies, scientists have suggested that normal physiological processes, such as the functional integrity of muscles and bone mass, can be affected by microgravity during spaceflight. During the life span, bone not only develops as a structure designed specifically for mechanical tasks but also adapts for efficiency. The lack of weight-bearing forces makes microgravity an ideal physical stimulus to evaluate bone cell responses. One of the most serious problems induced by long-term weightlessness is bone mineral loss. Results from in vitro studies that entailed the use of bone cells in spaceflights showed modification in cell attachment structures and cytoskeletal reorganization, which may be involved in bone loss. Humans exposed to microgravity conditions experience various physiological changes, including loss of bone mass, muscle deterioration, and immunodeficiency. In vitro models can be used to extract valuable information about changes in mechanical stress to ultimately identify the different pathways of mechanotransduction in bone cells. Despite many in vivo and in vitro studies under both real microgravity and simulated conditions, the mechanism of bone loss is still not well defined. The objective of this review is to summarize the recent research on bone cells under microgravity conditions based on advances in the field.

Case-control study on the associations between lifestyle-behavioral risk factors and phlegm-wetness constitution.

OBJECTIVE: To explore the relationships between different lifestyle-behavioral factors and phlegm-wetness type of Traditional Chinese Medicine constitution, so as to provide health management strategies for phlegm-wetness constitution. METHODS: A case-control study was conducted with the cases selected from the database of Chinese constitution survey in 9 provinces or municipalities of China. 1380 cases met the diagnostic criteria of phlegm-wetness type were taken as the case group, and 1380 cases were randomly selected from gentleness type as the control group. Using Chi-square test to compare the differences of lifestyle-behavior composition in each group; single factor and multiple logistic regression analysis were used to compare the relationships of lifestyle-behavioral factors and phlegm-wetness type. RESULTS: There were statistically significant differences between phlegm-wetness type group and gentleness type group in lifestyle behaviors (dietary habits, tobacco and liquor consumptions, exercise habits, sleeping habits). The results of single factor logistic regression analysis demonstrated that the risk of phlegm-wetness constitution decreased significantly in light diet (odds ratio, OR = 0.68); The risk factors of phlegm-wetness type were fatty food intake (OR = 2.36), sleeping early and getting up late (OR = 1.87), tobacco smoking (OR = 1.83), barbecued food intake (OR = 1.68), alcohol drinking (OR = 1.63), salty food intake (OR = 1.44), sleeping erratically (OR = 1.43), less physical activities (OR = 1.42), sweet food intake (OR = 1.29), sleeping and getting up late (OR = 1.26), and pungent food intake (OR = 1.21), respectively. Regardless of the interaction among lifestyle-behavioral factors, the results of the multiple logistic regression analysis revealed that the risk factors of phlegm-wetness type were sleeping early and getting up late (OR = 1.94), fatty food intake (OR = 1.80), tobacco smoking (OR = 1.50), sleeping erratically (OR = 1.50), barbecued food intake (OR = 1.40), sleeping and getting up late (OR = 1.40), less physical activities (OR = 1.31), sleeping late and getting up early (OR = 1.27), and sweet food intake (OR = 1.27, respectively, and the risk of phlegm-wetness type still decreased significantly in light food intake (OR = 0.79). CONCLUSION: Light diet can decrease the risk of being phlegm-wetness constitution, and bad lifestyle behaviors such as sleeping early and getting up late, sleeping erratically, fatty food, barbecued food or sweet food intake, tobacco and liquor consumptions, and less physical activities can increase the risks of becoming phlegm-wetness constitution.

[Correspondence analysis of chinese medical constitution features in different ages population].

OBJECTIVE: To explore the distribution features of Chinese medical constitutions in different ages population, thus providing scientific evidence of constitution process theory. METHODS: Recruited were 21 948 cases from a survey of Chinese medical constitutions and health conditions in 9 provinces or municipalities across China (including Jiangsu, Anhui, Gansu, Qinghai, Fujian, Beijing, Jilin, Jiangxi, and Henan) from Dec 2005 to Jan 2007. The body constitution type of individual was diagnosed using discriminant analysis on the basis of Chinese medical constitution questionnaire. By using correspondence analysis, the correlation between the general population, genders, ages, and Chinese medical constitution types was studied. RESULTS: Constitutions of yin-deficiency type, wetness-heat type, qi-depression type, and special diathesis type often occurred in the population ranging 15 -24 years old. Gentleness type mostly occurred in the population ranging 25 -44 years old. During this time period, phlegm-wetness type and wetness-heat type were liable to occur in males, while blood-stasis type was liable to occur in females. Qi-deficiency type and yang-deficiency type were most often seen in those older than 45 years. Phlegm-wetness type and blood-stasis type body constitution were also liable to occur in those older than 45 years. CONCLUSIONS: The distribution features were different in different Chinese medical constitutions. Different constitution types exist in different genders. Different constitution types exist different ages population.

Composition and constraints of lithium isotopes in cryoconite from various remote glacier areas of the Tibetan Plateau.

Lithium isotope is one of the most promising indicators for the study of continental silicate weathering, and lithium concentrations and its isotopic compositions in earth surface can provide a better understanding of the geochemical behavior and isotopic fractionation during weathering and erosion. This work focused on the composition and distribution of Li isotope in cryoconite deposited on various glacier areas in a large range of the Tibetan Plateau and surroundings, as well as its implications for cryoconite dust provenances. Results showed that δ7Li in cryoconite varied within the same order of magnitude (-2.14 ‰-7.74 ‰), which is characterized by geographic distribution of higher δ7Li value of cryoconite in northern glaciers (e.g. Yuzhufeng Glacier), and lower δ7Li value in southern glaciers. In comparison with other global materials, the cryoconite dust shows a lighter δ7Li isotopic composition due to constraints of climatic conditions and land surface weathering intensity. Compared with dust materials in the surrounding Asian dust sources (e.g. large deserts and Gobi), we find that, the primary sources of Li isotope in cryoconite of the northern locations were from both local dust/soils of the TP surface and the surrounding large deserts. Moreover, the products of anthropogenic activities (e.g. coal-burning) may also influence the isotopic composition of the cryoconite dust, and Li isotope may serve as potential tracers of anthropogenic source activities. Therefore, this work provides a complete view of the composition and distribution of Lithium isotopes in cryoconite from various glacier areas of the Tibetan Plateau, and the research significance of its transport processes and source constraints of Li isotopes in cryoconite is proposed.

Hospital volume-mortality association after esophagectomy for cancer: a systematic review and meta-analysis.

BACKGROUND: Postoperative mortality plays an important role in evaluating the surgical safety of esophagectomy. Although postoperative mortality after esophagectomy is partly influenced by the yearly hospital surgical case volume (hospital volume), this association remains unclear. METHODS: Studies assessing the association between hospital volume and postoperative mortality in patients who underwent esophagectomy for esophageal cancer were searched for eligibility. Odds ratios were pooled for the highest versus lowest categories of hospital volume using a random effects model. The dose-response association between hospital volume and the risk of postoperative mortality was analyzed. The study protocol was registered with PROSPERO. RESULTS: Fifty-six studies including 385 469 participants were included. A higher-volume hospital significantly reduced the risk of postesophagectomy mortality by 53% compared with their lower-volume counterparts (odds ratio, 0.47; 95% CI: 0.42-0.53). Similar results were found in subgroup analyses. Volume-outcome analysis suggested that postesophagectomy mortality rates remained roughly stable after the hospital volume reached a plateau of 45 esophagectomies per year. CONCLUSIONS: Higher-volume hospitals had significantly lower postesophagectomy mortality rates in patients with esophageal cancer, with a threshold of 45 esophagectomies per year for a high-volume hospital. This remarkable negative correlation showed the benefit of a better safety in centralization of esophagectomy to a high-volume hospital.

Methylation synthetic lethality: Exploiting selective drug targets for cancer therapy.

In cancer, synthetic lethality refers to the drug-induced inactivation of one gene and the inhibition of another in cancer cells by a drug, resulting in the death of only cancer cells; however, this effect is not present in normal cells, leading to targeted killing of cancer cells. Recent intensive epigenetic research has revealed that aberrant epigenetic changes are more frequently observed than gene mutations in certain cancers. Recently, numerous studies have reported various methylation synthetic lethal combinations involving DNA damage repair genes, metabolic pathway genes, and paralogs with significant results in cellular models, some of which have already entered clinical trials with promising results. This review systematically introduces the advantages of methylation synthetic lethality and describes the lethal mechanisms of methylation synthetic lethal combinations that have recently demonstrated success in cellular models. Furthermore, we discuss the future opportunities and challenges of methylation synthetic lethality in targeted anticancer therapies.

An adjustable multistage resistance switching behavior of a photoelectric artificial synaptic device with a ferroelectric diode effect for neuromorphic computing.

Neuromorphic computing, which mimics biological neural networks, is widely regarded as the optimal solution for addressing the limitations of traditional von Neumann computing architecture. In this work, an adjustable multistage resistance switching ferroelectric Bi2FeCrO6 diode artificial synaptic device was fabricated using a sol-gel method with a simple process. The device exhibits nonlinearity in its electrical characteristics, demonstrating tunable multistage resistance switching behavior and a strong ferroelectric diode effect through the manipulation of ferroelectric polarization. One of its salient advantages resides in its capacity to dynamically regulate its polarization state in response to an external electric field, thereby facilitating the fine-tuning of synaptic connection strength while maintaining synaptic stability. The device is capable of accurately simulating the fundamental properties of biological synapses, including long/short-term plasticity, paired-pulse facilitation, and spike-timing-dependent plasticity. Additionally, the device exhibits a distinctive photoelectric response and is capable of inducing synaptic plasticity by light signal activation. The utilization of a femtosecond laser for the scrutiny of carrier transport mechanisms imparts profound insights into the intricate dynamics governing the optical memory effect. Furthermore, utilizing a convolutional neural network (CNN) architecture, the recognition accuracy of the MNIST and fashion MNIST datasets was improved to 95.6% and 78%, respectively, through the implementation of improved random adaptive algorithms. These findings present a new opportunity for utilizing Bi2FeCrO6 materials in the development of artificial synapses for neuromorphic computation.

Development of a nanoparticle-based influenza vaccine using the PRINT technology.

Historically it is known that presentation of vaccine antigens in particulate form, for a wide range of pathogens, has clear advantages over the presentation of soluble antigen alone [J.C. Aguilar, E.G. Rodriguez, Vaccine adjuvants revisited. Vaccine 25 (2007) 3752-3762, M. Singh, D. O'Hagan, Advances in vaccine adjuvants. Nature Biotechnology 17 (1999) 1075-1081]. Herein we describe a novel particle-based approach, which independently controls size, shape, and composition to control the delivery and presentation of vaccine antigen to the immune system. Highly uniform particles were produced using a particle molding technology called PRINT (Particle Replication in Non-wetting Templates) which is an off-shoot of imprint lithography [J Am Chem Soc 127 (2005) 10096-10100, J Am Chem Soc 126 (2004) 2322-2323, Chem Soc Rev 35 (2006) 1095-1104, J Am Chem Soc 130 (2008) 5008-5009, J Am Chem Soc 130 (2008) 5438-5439, Polymer Reviews 47 (2007) 321-327, Acc Chem Res 41 (2008) 1685-1695, Acc Chem Res 44 (10) (2011) 990-998]. Cylindrical (diameter [d]=80 nm, height [h]=320 nm) poly (lactide-co-glycolide) (PLGA) based PRINT particles were designed to electrostatically bind commercial trivalent injectable influenza vaccine. In a variety of blended PLGA formulations, these particles were safe and showed enhanced responses to influenza hemagglutinin in murine models. FROM THE CLINICAL EDITOR: Shape is one of the determining factors in interactions of nanoparticles with their biologic environment. PRINT technology is able to fabricate nearly uniform nanoparticles and this technology is tested here in murine models to effectively deliver influenza vaccine.

Correlation between tobacco and alcohol use and Traditional Chinese Medicine constitutions: an analysis based on a sample from general population of China.

OBJECTIVE: To investigate the relationship between smoking and drinking and constitution types from Traditional Chinese Medicine (TCM) theory. METHODS: The Constitution in Chinese Medicine Questionnaire (CCMQ) was used. A sample of 8448 subjects from nine provinces and municipalities was chosen from the database of the TCM constitution and health status survey. Constituent ratio and correspondence analysis were used to find the relationship between smoking and drinking and TCM constitution. RESULTS: There was an association between smoking and drinking and the Gentleness, phlegm-dampness, and dampness-heat type constitutions. People that did not smoke tobacco or drink alcohol tended to have Yang-deficiency, Yin-deficiency, Qi-depression, Qi-deficiency, special diathesis, or blood-stasis type constitutions. CONCLUSION: There was a significant correlation between tobacco and alcohol use and TCM constitutions. To improve patient health, more attention should be paid to tobacco and alcohol control.

Impact of government subsidies on innovation of Chinese biopharmaceutical firms: Based on kink threshold model.

Do government subsidies achieve the goals of stimulating firm innovation and macro-regulation? Existing studies have not reached a consistent conclusion. We will study the incentive effect of government subsidies on innovation of biopharmaceutical firms, analyze the optimal interval of government subsidies, and improve the efficiency of government subsidies. Thus, based on kink threshold model using data from Chinese biopharmaceutical listed companies from 2013-2019, this study analyzes the impact of government subsidies on innovation inputs and outputs. Government subsidies can stimulate innovation inputs and outputs of biopharmaceutical firms. Meanwhile, such subsidies have a significant threshold effect on innovation inputs and outputs, and there is an optimal interval effect. Additionally, concerning enterprise ownership, government subsidies have a more significant role in promoting innovation of non-state biopharmaceutical firms. Regarding regional differences, such subsidies have a more significant role in promoting innovation of firms in the less economically developed central and western regions. This study reveals the influence pattern of government subsidies, and provides insights and suggestions to formulate subsidy policies and enhance innovation.

Life expectancy and healthy life expectancy of patients with advanced schistosomiasis in Hunan Province, China.

BACKGROUND: Few studies have investigated the change in life expectancy (LE) and the healthy lifespan among patients with advanced schistosomiasis. This study was to evaluate the LE and healthy life expectancy (HLE) for patients and assess the mechanism responsible for the LE inequality. METHODS: We utilized data from a dynamic advanced schistosomiasis cohort (10,362 patients) for the period from January 2008 to December 2019 in Hunan Province, China, to calculate the LEs of patients, and made a comparison with that of general population (19,642 schistosomiasis-free individuals) in the schistosomiasis endemic areas. LEs were estimated from 15 years of age by constructing period life tables. Arriaga's decomposition method was applied to quantify the influence of the age structure on the difference in LE. HLE for advanced schistosomiasis patients was calculated by using Sullivan method with age-specific disability weight. The LE and HLE were calculated for both males and females to perform further analyses on gender gap. RESULTS: The estimated LE for advanced schistosomiasis patients aged 15-19 was 49.51 years (48.86 years for males and 51.07 years for females), which was 20.14 years lower compared with general population (69.65 years), and the LE gap between patients and general population decreased with age. The largest age-specific mortality contribution to the gap (32.06%) occurred at age 80-84 years. Women had a lower LE and HLE than men at age ≥ 60 years (both gender gaps in LE and HLE < 0). For advanced schistosomiasis patients, the gender gap in LE was largely attributed to the difference in mortality among those under the age of 55; the age-specific mortality in women exerted positive influence on the gap at age 25-64 and 75-79 years, with the contribution rate ranging from 0.59% to 57.02%, and made the negative contribution at other age groups. CONCLUSIONS: The LE of advanced schistosomiasis patients was still much lower compared with general population. Strengthened prevention strategies and targeted treatments are needed to reduce morbidity and mortality due to advanced schistosomiasis, especially for younger population and elderly female patients.

nNOS downregulation attenuates neuronal apoptosis by inhibiting nNOS-GluR6 interaction and GluR6 nitrosylation in cerebral ischemic reperfusion.

Glutamate receptor 6 (GluR6) is well documented to play a pivotal role in ischemic brain injury, which is mediated by the GluR6·PSD95·MLK3 signaling module and subsequent c-Jun N-terminal kinase (JNK) activation. Our recent studies show that GluR6 is S-nitrosylated in the early stages of ischemia-reperfusion. NO (Nitric Oxide) is mainly generated from neuronal nitric oxide synthase (nNOS) in cerebral neurons during the early stages of reperfusion. Here, the effect of nNOS downregulation on GluR6 S-nitrosylation and GluR6-mediated signaling was investigated in cerebral ischemia and reperfusion. Administration of nNOS oligonucleotides confirmed that GluR6 nitrosylation is induced by nNOS-derived endogenous NO and further activates the GluR6·PSD95·MLK3 signaling module and JNK signaling pathway. Moreover, this study revealed for the first time that nNOS can bind with GluR6 during ischemic reperfusion, and PSD95 is involved in this interaction. In summary, our results suggest that nNOS binds with GluR6 via PSD95 and then produces endogenous NO to S-nitrosylate GluR6 in cerebral ischemia-reperfusion, which provides a new approach for stroke therapy.

Expression, purification, and characterization of RGD-mda-7, a His-tagged mda-7/IL-24 mutant protein.

RGD peptide (Arg-Gly-Asp tripeptide) binds to integrin αVß(3) and αVß(5), which is selectively expressed in tumor neovasculature and on the surface of some tumor cells. Some studies showed that coupling the RGD peptides to anticancer drugs yielded compounds with increased efficiency against tumors and lowered toxicity to normal tissues. The melanoma differentiation-associated gene-7/interleukin-24 gene (mda-7/IL-24) is a novel tumor-suppressor/cytokine gene that exhibits potent tumor-suppressive activity without damaging normal cells. To enhance the antitumor effect, we inserted a glycine residue into the wild type (mda-7/IL-24) between (164)Arg and (165)Asp to form a RGD peptide, named RGD-mda-7, then expressed RGD-mda-7 in Escherichia coli. Herein, we describe the expression and purification of RGD-mda-7. We detected the characterizations of immunostimulatory activity, tumor targeting, potent cytopathic effect, and apoptosis inducing exploited by RGD-mda-7 in tumor cells, and also compared these characterizations with wtmda-7/IL-24. The data showed that RGD-mda-7 had more potent tumor targeting and apoptosis-inducing effects than wtmda-7/IL-24.

Responsiveness of three subjective report of outcome measures for chronic heart failure.

OBJECTIVE: To compare the responsiveness of a newly designed symptom scale, the Chinese Medical Symptom Rating Scale for Heart Failure (CMSRS-HF), with the Chinese version of Minnesota Living with Heart Failure Questionnaire (MLHFQ) and the Medical Outcomes Study Short-form 36 (SF-36), and provide basis for the selection of subjective outcome measures for clinical evaluation of treatment of chronic heart failure by integrated traditional Chinese and Western medicine. METHODS: One hundred and fifty-six patients with chronic heart failure were recruited from three clinical centers and were treated with Chinese herbal medicine based on syndrome classification. The patients were classified with standard of New York Heart Association and evaluated with CMSRS-HF, MLHFQ and SF-36. Three techniques for the quantification of responsiveness were utilized: paired t-test, effect sizes (ES) and standardized response means (SRM). RESULTS: a) After 2-week treatment, patients scored significantly lower in CMSRS-HF, while scores of each dimension on MLHFQ and SF-36 increased significantly (P=0.000). b) ES of CMSRS-HF was greater than 0.8. ES of physical and emotional dimensions and comprehensive scores of MLHFQ were between 0.37 and 0.61; ES of each dimension, physical and emotional domains, and comprehensive scores were between 0.14 and 0.49. c) SRM of CMSRS-HF was greater than 0.8; SRM of physical and emotional dimensions and comprehensive scores of MLHFQ ranged from 0.53 to 0.92; SRM of each dimension, physical and emotional domains, and comprehensive scores were between 0.23 and 0.83. d) By stratified analysis according to NYHA classification, the acute patients (NYHA III, IV) were more sensitive to subjective outcome measures. CONCLUSION: Responsiveness of the newly designed CMSRS-HF is high. However, responsiveness of MLHFQ and most dimensions in SF-36 is moderate. When evaluating clinical effects of integrated traditional Chinese and Western medicine on chronic heart failure, different scales can be applied according to actual clinical presentations.

A method of detecting apple leaf diseases based on improved convolutional neural network.

Apple tree diseases have perplexed orchard farmers for several years. At present, numerous studies have investigated deep learning for fruit and vegetable crop disease detection. Because of the complexity and variety of apple leaf veins and the difficulty in judging similar diseases, a new target detection model of apple leaf diseases DF-Tiny-YOLO, based on deep learning, is proposed to realize faster and more effective automatic detection of apple leaf diseases. Four common apple leaf diseases, including 1,404 images, were selected for data modeling and method evaluation, and made three main improvements. Feature reuse was combined with the DenseNet densely connected network and further realized to reduce the disappearance of the deep gradient, thus strengthening feature propagation and improving detection accuracy. We introduced Resize and Re-organization (Reorg) and conducted convolution kernel compression to reduce the calculation parameters of the model, improve the operating detection speed, and allow feature stacking to achieve feature fusion. The network terminal uses convolution kernels of 1 × 1, 1 × 1, and 3 × 3, in turn, to realize the dimensionality reduction of features and increase network depth without increasing computational complexity, thus further improving the detection accuracy. The results showed that the mean average precision (mAP) and average intersection over union (IoU) of the DF-Tiny-YOLO model were 99.99% and 90.88%, respectively, and the detection speed reached 280 FPS. Compared with the Tiny-YOLO and YOLOv2 network models, the new method proposed in this paper significantly improves the detection performance. It can also detect apple leaf diseases quickly and effectively.