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.

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.

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.

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.

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.

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.

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.

Insight into atmospheric deposition and spatial distribution of bioavailable iron in the glaciers of northeastern Tibetan Plateau.

Iron (Fe) is an essential micronutrient in glacial ecosystems and modulates global biogeochemical cycles. To find out the deposition concentration, multiple origins and release form of iron in various glacier areas of central Asia, this study investigated the total Fe (TFe) and dissolved-Fe (dFe, diameter < 0.45 or <0.2 µm) deposition in glaciers and snowpack of northeast Tibetan Plateau, based on snow and meltwater sampling in ablation period of 2014-2017. The composition and concentration of dFe in the samples were measured, and the spatial distribution and temporal variations of dFe in glacial surface snow and meltwater runoff were investigated. Results showed that average TFe and dFe contents exhibited a generally heterogeneous geographic distribution that varied from north to south. The northern locations in eastern Tianshan Mountains (e.g. Miaoergou Glacier) showed the highest TFe and dFe values, followed by Yuzhufeng Glacier of eastern Kunlun Mountains, whereas the Qilian Mountains locations displayed relatively lower TFe and dFe contents spanning a wide range. Based on the good correlation between TFe and dFe, we infer that aeolian dust and anthropogenic aerosols, and their chemical interactions are likely the important origins for dFe deposition. In meltwater runoff the peak values of dFe release flux appeared in July, with maximum appeared earlier (the early of July) than TFe (the end of July). Moreover, the annual dFe release flux from Laohugou glacier terminus meltwater runoff is estimated to be 1740 kg yr-1 (with 9256 kg yr-1 for TFe), and meltwater showed higher mean concentration of dFe than that of glacier snowpack. We also provided a conceptual framework showing the multiple origins and transport dynamics of dissolved Fe along the atmosphere-glacier-meltwater runoff path. Compared to Fe release in other global glacier/ice-sheet, the TP glacier is an important potential dFe reservoir and may have a profound effect on regional downstream ecosystem through Fe biochemistry cycle.

A highly conductive self-assembled multilayer graphene nanosheet film for electronic tattoos in the applications of human electrophysiology and strain sensing.

Highly conductive, conformable and gel-free electrodes are desirable in human electrophysiology. Besides, intimately coupling with human skin, wearable strain sensors can detect numerous physiological signals, such as wrist pulse and breath. In this study, a multilayer graphene nanosheet film (MGNF) with high conductivity was prepared by the Marangoni self-assembly for using in tattoo dry electrodes (TDEs) and in a graphene tattoo strain sensor (GTSS). Compared to commercial Ag/AgCl gel electrodes, TDEs have lower skin-electrode contact impedance and could detect human electrocardiogram for 24-hour wearing more accurately as well as electromyogram. Through designing a slim serpentine ribbon structure, a resistance-type GTSS, without deterioration even after 2000 cycles, is well demonstrated for human wrist pulse and breath sensing. With the advantages of high conductivity and conformability, MGNF provides support to fabricate low-cost, customizable, and high-performance electronic tattoos for human electrophysiology and strain sensing.

Early rehabilitation nursing in ICU promotes rehabilitation of patients with respiratory failure treated with invasive mechanical ventilation.

OBJECTIVE: This paper aimed at exploring the application value of early rehabilitation nursing (ERN) in intensive care unit (ICU) for nursing patients with respiratory failure (RF) treated with invasive mechanical ventilation (IMV). METHODS: Admitted to the ICU of our hospital from January 2019 to June 2020, 172 RF patients that was treated with IMV were selected as the research objects. Those in the general group (n=80) received routine nursing in ICU, whereas those in the recovery group (n=92) received ERN on the basis of the general group. The recovery of their vital signs, blood gas functions and pulmonary functions was monitored. Their treatment time in ICU, mechanical ventilation time (MVT), total hospitalization time (THT) and incidence of complications were recorded. Their negative emotions, quality of life (QOL) and nursing satisfaction were assessed. RESULTS: After intervention, the body temperature, the respiratory rate and the heart rate in the recovery group were lower than those in the general group (P<0.05). The arterial partial pressure of oxygen (PaO2) and blood oxygen saturation (SpO2) were remarkably higher in the recovery group, while the arterial partial pressure of carbon dioxide (PaCO2) was remarkably lower (P<0.05). One-second forced expiratory volume (FEV1), FEV1/forced vital capacity (FVC) and FEV1% were remarkably higher in the recovery group (P<0.05). The treatment time in ICU, the MVT and the THT were remarkably shorter in the recovery group (P<0.05). During intervention, the total incidence of complications was lower in the recovery group (P<0.05). While after intervention, the scores of the Self-rating Anxiety Scale (SAS), the Self-rating Depression Scale (SDS) and the St. George's Respiratory Questionnaire (SGRQ; symptom, activity, impact) were lower in the recovery group, but the nursing satisfaction was remarkably higher (P<0.05). CONCLUSION: During the treatment of RF patients with IMV, ERN can promote their recovery, reduce the incidence of complications, relieve their negative emotions, and improve their QOL and nursing satisfaction. So, this nursing model is worthy of clinical application.

Cluster nursing can reduce postoperative delirium and improve the negative emotions and quality of life of elderly ICU patients.

OBJECTIVE: To explore the application effect of cluster nursing in post-surgery elderly patients in intensive care units (ICU). METHODS: From March 2019 to August 2020, a total of 167 elderly patients admitted to the ICU in Changzhou No. 2 People's Hospital, the Affiliated Hospital of Nanjing Medical University were recruited as the study cohort. They were divided into a test group (n=85) and a control group (n=82). The patients in the control group underwent routine nursing, and the patients in the test group underwent cluster nursing in addition to the nursing the control group underwent. The two groups' incidences of delirium, their quality of life, and their mental health were compared. RESULTS: The total incidences of delirium in the test group were significantly lower than they were in the control group, and the delirium outcome rate was significantly higher than it was in the control group. A comparison of the Acute Physiology and Chronic Health Evaluation (APACHE ll) and Symptom Checklist-90 (SCL-90) scores before and after the nursing showed that the test group had notably lower scores than the control group. In addition, the nursing satisfaction rate in the test group was 88.24%, which was significantly higher than the rate in the control group (73.17%). The hospitalization expenses of the test group were lower, with a notably improved quality of life. CONCLUSION: Cluster nursing can reduce the incidence of delirium and improve the quality of life and mental health of post-surgery elderly ICU patients.

Mutation of the BAG-1 domain decreases its protective effect against hypoxia/reoxygenation by regulating HSP70 and the PI3K/AKT signalling pathway in SY-SH5Y cells.

BCL-2-associated athanogene-1 (BAG-1) is a multifunctional protein that was first identified as a binding partner of BCL-2. Our previous results indicated that BAG-1 large (BAG-1L) overexpression significantly increases cell viability and decreases apoptosis by upregulating HSP70 and p-AKT in response to hypoxia/reoxygenation in SY-SH5Y cells. However, the functional domain of BAG-1L that exerts these protective effects against hypoxic damage has not been identified. In this study, we examined changes in HSP70 and p-AKT protein levels in SH-SY5Y cells with or without BAG-1L domain mutation after six hours of hypoxia/reoxygenation treatment. The BAG-1 domain mutant (BAG-1MUT) attenuated neuronal viability and proliferation while enhancing apoptosis after hypoxia/reoxygenation, which was achieved in part by inhibiting the HSP70 and p-AKT signalling pathways. This evidence illustrates that the BAG-1 domain plays a key role in protecting cells from hypoxia/reoxygenation injury.

Accuracy Evaluation of Five Blood Glucose Monitoring Systems in Patients from Different Departments.

BACKGROUND: Self-monitoring of blood glucose (SMBG) systems are expected to be accurate and provide reliable results. The international standard ISO (International Organization for Standardization) 15197:2013 is widely accepted for the accuracy evaluation for SMBG systems. Accuracy evaluation was performed for 5 different SMBG systems in patients from multi-departments at the hospital. METHOD: A total of 120 patients from Changzhou Second People's Hospital (Changzhou, China) were randomized and enrolled in the study. Accuracy evaluation was performed for 5 different SMBG systems: Gold AQ (Sinocare), Freestyle Optium Xceed (Abbott), Contour TS (Bayer), OneTouch Ultra (J&J) and Accu-Chek Performa (Roche). For each system, comparison measurements were performed with YSI 2300 STAT PLUS Glucose and Lactate Analyzer and Roche Cobas 8000 Modular Analyzer. RESULTS: All 5 systems showed that 100% of results fall within consensus error grid Zones A and B. Compared with YSI 2300 or Roche Cobas 8000 Modular Analyzer, Gold AQ system showed the highest accuracy. The linearity analysis also showed that Gold AQ had the highest correlation coefficient. CONCLUSION: Compared with other SMBG systems, Gold AQ Glucose Monitoring System manufactured by Sinocare Inc. had the highest accuracy in measuring blood glucose level in patients from multi-departments at this hospital.

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.

1,8-Naphthalimide-Based Multifunctional Compounds as Cu2+ Probes, Lysosome Staining Agents, and Non-viral Vectors.

A series of multifunctional compounds (MFCs) 1a-1d based on 1,8-naphthalimide moiety were designed and synthesized. Due to the good fluorescence property and nucleic acid binding ability of 1,8-naphthalimide, these MFCs were applied in Cu2+ ion recognition, lysosome staining as well as RNA delivery. It was found that these MFCs exhibited highly selective fluorescence turn-off for Cu2+ in aqueous solution. The fluorescence emission of 1a-1d was quenched by a factor of 116-, 20-, 12-, and 14-fold in the presence of Cu2+ ions, respectively. Most importantly, 1a-Cu and 1b-Cu could be used as imaging reagents for detection of lysosome in live human cervical cancer cells (HeLa) using fluorescence microscopy. Furthermore, in order to evaluate the RNA delivery ability of 1a-1d, cellular uptake experiments were performed in HeLa, HepG2, U2Os, and MC3T3-E1 cell lines. The results showed that all the materials could deliver Cy5-labled RNA into the targeted cells. Among them, compound 1d modified with long hydrophobic chain exhibited the best RNA delivery efficiency in the four tested cell lines, and the performance was far better than lipofectamine 2000 and 25 kDa PEI, indicating the potential application in non-viral vectors.

[Preliminary study on the effect of lipopolysaccharide challenge on the genes expression of inflammatory factors in A549 cells].

OBJECTIVE: To explore the effects of lipopolysaccharide (LPS) on the expression of inflammatory genes in A549 cells line under different concentrations and different action time, this study laid the foundation for further establishment of acute respiratory distress syndrome (ARDS) cell model in the optimal concentration-time way. METHODS: A549 cells line was incubated routinely in 5% CO2 incubator at 37 centigrade with high glucose DMEM medium which included 10% fetal calf serum. Cells in logarithmic phase was cultured for passage, the cells was count to adjust cell density to (5-7)×105 and tile evenly in six-hole plate. Cells were cultivated for 2 days and once the cells confluence to 50%-60%, serum-free medium DMEM was changed for 12 hours cultivation. 10 mg LPS was added to 10 mL DMEM for oscillated blending to prepare 1 g/L stock solution. 0.5, 1.0 and 2.5 mL LPS stock solution was taken respectively and diluted LPS stock solution for 50 mL constant volume to prepare 0, 10, 20 and 50 mg/L LPS working solution. Then 0, 10, 20 and 50 mg/L LPS solution was added to react for 0, 1, 3 and 5 hours respectively. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to examine mRNA expression of A549 cells line interleukins (IL-6, IL-1ß) and tumor necrosis factor-α (TNF-α). LPS action of 10 mg/L for 0 hour was used as the time control group, LPS action of 0 mg/L for 1 hour was used as the concentration control group, and the gene expression was calculated with 2-ΔΔCt method. RESULTS: (1) As to the time factor, with the same action of LPS concentration, the relative expression levels of inflammatory genes (IL-6, IL-1ß and TNF-α) in A549 cells line after being treated with 10 mg/L LPS for 1 hour were significantly higher than those for 0 hour respectively [IL-6 mRNA (2-ΔΔCt): 5.71±0.42 vs. 1.00±0.00, IL-1ß mRNA (2-ΔΔCt): 5.63±0.30 vs. 1.00±0.00, TNF-α mRNA (2-ΔΔCt): 5.38±0.61 vs. 1.00±0.00, all P < 0.01], and there were no significant changes in the expression levels of inflammatory genes in A549 cells line of other time groups. (2) As to the concentration factor, with the same action time, the relative expression levels of inflammatory genes (IL-6, IL-1ßand TNF-α) in A549 cells line after being treated with 10 mg/L LPS for 1 hour were significantly higher than with 0 mg/L for 1 hour respectively [IL-6 mRNA (2-ΔΔCt): 5.70±0.64 vs. 1.00±0.00, IL-1ß mRNA (2-ΔΔCt): 6.25±0.25 vs. 1.00±0.00, TNF-α mRNA (2-ΔΔCt): 5.57±0.25 vs. 1.00±0.00, all P < 0.01], there were no significant changes in the expression levels of inflammatory genes in A549 cells line of other concentration groups. CONCLUSIONS: The LPS concentration of 10 mg/L and the action time of 1 hour are the most suitable concentration-time conditions for establishing ARDS cell models of A549 cells line.

A prospective longitudinal evaluation of cognition and depression in postoperative patients with high-grade glioma following radiotherapy and chemotherapy.

AIM OF STUDY: The survival rate in high-grade glioma (HGG) patients receiving a combined regimen of radiotherapy (RT) and temozolomide after tumor resection was increased. However, cognitive deficits and depression after the treatments challenge the treatments. The aim of this study was to evaluate the cognition and depression in postoperative patients with HGG following RT and chemotherapy. MATERIALS AND METHODS: Six-five eligible patients were included in the study. Cognition and depression were examined at baseline (after surgery before RT), every 3 months during follow-up using mini-mental state examination and Zung Self-Rating Depression Scale (SDS), respectively. RESULTS: Our results showed that cognition was not significantly affected after treatments (F = 1.19, P = 0.32). However, significant differences between baseline and follow-ups were found regarding SDS scores (F = 3.26, P =0.0.01). SDS score at the 3rd month was significantly higher than that at baseline (t = -3.16, P = 0.002). CONCLUSION: This prospective study showed that although cognition was not significantly affected, the treatment caused depression, particularly at the 3rd month. These data implicated that interventions should be designed to deal with depression in the 3rd month.

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.