Erlotinib combination with a mitochondria-targeted ubiquinone effectively suppresses pancreatic cancer cell survival

BACKGROUND Pancreatic cancer is a leading cause of cancer-related deaths.Increased activity of the epidermal growth factor receptor(EGFR)is often observed in pancreatic cancer,and the small molecule EGFR inhibitor erlotinib has been approved for pancreatic cancer therapy by the food and drug administration.Nevertheless,erlotinib alone is ineffective and should be combined with other drugs to improve therapeutic outcomes.We previously showed that certain receptor tyrosine kinase inhibitors can increase mitochondrial membrane potential(Δψm),facilitate tumor cell uptake ofΔψm-sensitive agents,disrupt mitochondrial homeostasis,and subsequently trigger tumor cell death.Erlotinib has not been tested for this effect.AIM To determine whether erlotinib can elevateΔψm and increase tumor cell uptake ofΔψm-sensitive agents,subsequently triggering tumor cell death.METHODSΔψm-sensitive fluorescent dye was used to determine how erlotinib affectsΔψm in pancreatic adenocarcinoma(PDAC)cell lines.The viability of conventional and patient-derived primary PDAC cell lines in 2D-and 3D cultures was measured after treating cells sequentially with erlotinib and mitochondria-targeted ubiquinone(MitoQ),aΔψm-sensitive MitoQ.The synergy between erlotinib and MitoQ was then analyzed using SynergyFinder 2.0.The preclinical efficacy of the twodrug combination was determined using immune-compromised nude mice bearing PDAC cell line xenografts.RESULTS Erlotinib elevatedΔψm in PDAC cells,facilitating tumor cell uptake and mitochondrial enrichment ofΔψm-sensitive agents.MitoQ triggered caspase-dependent apoptosis in PDAC cells in culture if used at high doses,while erlotinib pretreatment potentiated low doses of MitoQ.SynergyFinder suggested that these drugs synergistically induced tumor cell lethality.Consistent with in vitro data,erlotinib and MitoQ combination suppressed human PDAC cell line xenografts in mice more effectively than single treatments of each agent.CONCLUSION Our findings suggest that a combination of erlotinib and MitoQ has the potential to suppress pancreatic tumor cell viability effectively.

Modified intratympanic steroid therapy for sudden sensorineural hearing loss via tympanic tube and gelfoam as a salvage treatment

Background: Sudden sensorineural hearing loss(SSNHL) is a prevalent emergency in ear, nose, and throat practice. Previous studies have demonstrated that intratympanic steroid therapy(IST) can serve as a salvage treatment for SSNHL after the failure of systemic steroid therapy(SST).Objective: This study aimed to analyze the efficacy of modified IST involving the insertion of a tympanic tube and gelfoam as a salvage treatment for patients with SSNHL, and to explore its associated factors.Methods: Totally, 74 patients who were aged 22–81 years with SSNHL were enrolled and allocated to either the control group(n = 25) or the treatment group(n = 49) based on their treatment modalities. All patients received SST lasting for at least 7 days. Subsequently, patients in the treatment group, after SST failure, underwent IST twice a week for 2–6 weeks, while the control group did not. Efficacy was assessed by the improvement in pure tone average at the affected frequency at the beginning and end of IST.Results: Hearing improvement in all patients after IST in the treatment group was 9.71 ± 14.84 dB, with significant improvement at affected frequencies(250-8000 Hz) compared with the control group(P < 0.05). The findings indicated the duration from the onset of SSNHL to the beginning of IST as an independent factor for pure tone average improvement after treatment(P = 0.002), whereas age, duration of SST, and time of IST were not(P > 0.05).Conclusion: The modified IST was demonstrated to be a safe and effective method as a salvage treatment for SSNHL. This study explored the efficacy of a modified IST approach, incorporating the utilization of tympanic tubes and gelfoam as key components. The findings underscore the advantages of gelfoam as a strategic drug carrier placed in the round window niche. By minimizing drug loss, extending action time, and increasing perilymph concentration, gelfoam enhances the therapeutic impact of IST, contributing to improved hearing outcomes in patients with SSNHL.

Response Mechanisms to Flooding Stress in Mulberry Revealed by Multi-Omics Analysis

Abiotic stress,including flooding,seriously affects the normal growth and development of plants.Mulberry(Morus alba),a species known for its flood resistance,is cultivated worldwide for economic purposes.The transcriptomic analysis has identified numerous differentially expressed genes(DEGs)involved in submergence tolerance in mulberry plants.However,a comprehensive analyses of metabolite types and changes under flooding stress in mulberry remain unreported.A non-targeted metabolomic analysis utilizing liquid chromatographytandem mass spectrometry(LC-MS/MS)was conducted to further investigate the effects of flooding stress on mulberry.A total of 1,169 metabolites were identified,with 331 differentially accumulated metabolites(DAMs)exhibiting up-regulation in response to flooding stress and 314 displaying down-regulation.Pathway enrichment analysis identified significant modifications in many metabolic pathways due to flooding stress,including amino acid biosynthesis and metabolism and flavonoid biosynthesis.DAMs and DEGs are significantly enriched in the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways for amino acid,phenylpropanoid and flavonoid synthesis.Furthermore,metabolites such as methyl jasmonate,sucrose,and D-mannose 6-phosphate accumulated in mulberry leaves post-flooding stress.Therefore,genes and metabolites associated with these KEGG pathways are likely to exert a significant influence on mulberry flood tolerance.This study makes a substantial contribution to the comprehension of the underlying mechanisms implicated in the adaptation of mulberry plants to submergence.

A Biomass-Based Hydrogel Evaporator Modified Through Dynamic Regulation of Water Molecules:Highly Efficient and Cost-Effective

Solar-driven hydrogel evaporator used for water purification demonstrates great potential in seawater desalination and domestic sewage treatment.However,much uncertainty still exists about the most efficient design to obtain cost-effective drinkable water.In this paper,a natural rich biomass Nicandra physalodes(Linn.)Gaertn.polysaccharide was introduced into the polyvinyl alcohol network to control the water distribution during evaporation and build a low-cost hybrid hydrogel solar evaporator with a total material cost of$7.95 m^(−2).The mixed evaporator works stably in a long-span acid–base range(pH 1–14)and salinity range(0–320 g kg^(−1)).Its daily water purification capacity can reach 24.4 kg m^(−2)with a water purification capacity of 3.51 kg m^(−2)h^(−1)under sunlight.This paper provides a new possibility for a highly efficient and cost-effective water desalination system with guaranteed water quality by focusing on the dynamic regulation of water molecules at the evaporation interface.

DDG1 and G Protein α Subunit RGA1 Interaction Regulates Plant Height and Senescence in Rice(Oryza sativa)

Many studies have already shown that dwarfism and moderate delayed leaf senescence positively impact rice yield,but the underlying molecular mechanism of dwarfism and leaf senescence remains largely unknown.Here,using map-based cloning,we identified an allele of DEP2,DDG1,which controls plant height and leaf senescence in rice.The ddg1 mutant displayed dwarfism,short panicles,and delayed leaf senescence.Compared with the wild-type,ddg1 was insensitive to exogenous gibberellins(GA)and brassinolide(BR).DDG1 is expressed in various organs,especially in stems and panicles.Yeast two-hybrid assay,bimolecular fluorescent complementation and luciferase complementation image assay showed that DDG1 interacts with theα-subunit of the heterotrimeric G protein.Disruption of RGA1 resulted in dwarfism,short panicles,and darker-green leaves.Furthermore,we found that ddg1 and the RGA1 mutant was more sensitive to salt treatment,suggesting that DDG1 and RGA1 are involved in regulating salt stress response in rice.Our results show that DDG1/DEP2 regulates plant height and leaf senescence through interacting with RGA1.

Interface engineering yields efficient perovskite light-emitting diodes

Metal-halide perovskites(MHPs)have emerged as a new class of semiconductors used in perovskite solar cells(PSCs)[1-5],perovskite light-emitting diodes(PeLEDs)[6-12],photo/X-ray detectors[13-16],and memristors[17,18].Pe LEDs can emit different light with high purity[19,20].

Effects of non-starch polysaccharide on starch gelatinization and digestibility:a review

Non-starch polysaccharides have been given wide consideration for their use in starch-based food due to their ability to improve texture,sensory attributes,and functional properties of the end product.In a binary system(starch and non-starch polysaccharides),the characteristics of starch,exemplified as gelatinization and digestibility undergo significant changes.This review article,through a combination of origin and chemical structure-based classification approach,explores the impact of non-starch polysaccharides on starch behavior,concretely for gelatinization and hydrolysis.The underlying mechanism to retard gelatinization gives rise to some colloids that can reduce water accessibility and interact with starch molecules,which vary with the origin.The interfering role of starch hydrolysis attributed to polysaccharides restrict starch swelling,the bulk viscosity,and more ordered structures occur in the mixture.Besides,the role of non-starch polysaccharides on enzymes is another factor.Therefore,this paper gives an overview of how non-starch polysaccharides interfere with starch gelatinization and digestion,which provides a comprehensive understanding of starchy products.

Effect of low-level laser therapy on tooth-related pain and somatosensory function evoked by orthodontic treatment

Low-level laser therapy(LLLT) may have an effect on the pain associated with orthodontic treatment. The aim of this study was to evaluate the effect of LLLT on pain and somatosensory sensitization induced by orthodontic treatment. Forty individuals(12–33 years old; mean ± standard deviations: 20.8 ± 5.9 years) scheduled to receive orthodontic treatment were randomly divided into a laser group(LG) or a placebo group(PG)(1:1). The LG received LLLT(810-nm gallium-aluminium-arsenic diode laser in continuous mode with the power set at 400 mW, 2 J·cm–2) at 0 h, 2 h, 24 h, 4 d, and 7 d after treatment, and the PG received inactive treatment at the same time points. In both groups, the non-treated side served as a control. A numerical rating scale(NRS) of pain, pressure pain thresholds(PPTs), cold detection thresholds(CDTs), warmth detection thresholds(WDTs), cold pain thresholds(CPTs), and heat pain thresholds(HPTs) were tested on both sides at the gingiva and canine tooth and on the hand. The data were analysed by a repeated measures analysis of variance(ANOVA). The NRS pain scores were significantly lower in the LG group(P = 0.01). The CDTs,CPTs, WDTs, HPTs, and PPTs at the gingiva and the PPTs at the canine tooth were significantly less sensitive on the treatment side of the LG compared with that of the PG(P < 0.033). The parameters tested also showed significantly less sensitivity on the nontreatment side of the LG compared to that of the PG(P < 0.043). There were no differences between the groups for any quantitative sensory testing(QST) measures of the hand. The application of LLLT appears to reduce the pain and sensitivity of the tooth and gingiva associated with orthodontic treatment and may have contralateral effects within the trigeminal system but no generalized QST effects. Thus, the present study indicated a significant analgesia effect of LLLT application during orthodontic treatment.Further clinical applications are suggested.

Integration of high-performance spin-orbit torque MRAM devices by 200-mm-wafer manufacturing platform

We demonstrate in-plane field-free-switching spin-orbit torque(SOT)magnetic tunnel junction(MTJ)devices that are capable of low switching current density,fast speed,high reliability,and,most importantly,manufactured uniformly by the 200-mm-wafer platform.The performance of the devices is systematically studied,including their magnetic properties,switch-ing behaviors,endurance and data retention.The successful integration of SOT devices within the 200-mm-wafer manufactur-ing platform provides a feasible way to industrialize SOT MRAMs.It is expected to obtain excellent performance of the devices by further optimizing the MTJ film stacks and the corresponding fabrication processes in the future.

WiFi CSI Gesture Recognition Based on Parallel LSTM-FCN Deep Space-Time Neural Network

In this study,we developed a system based on deep space–time neural networks for gesture recognition.When users change or the number of gesture categories increases,the accuracy of gesture recognition decreases considerably because most gesture recognition systems cannot accommodate both user differentiation and gesture diversity.To overcome the limitations of existing methods,we designed a onedimensional parallel long short-term memory–fully convolutional network(LSTM–FCN)model to extract gesture features of different dimensions.LSTM can learn complex time dynamic information,whereas FCN can predict gestures efficiently by extracting the deep,abstract features of gestures in the spatial dimension.In the experiment,50 types of gestures of five users were collected and evaluated.The experimental results demonstrate the effectiveness of this system and robustness to various gestures and individual changes.Statistical analysis of the recognition results indicated that an average accuracy of approximately 98.9% was achieved.

有机化学实验混合式教学研究与实践--以“乙醚的制备”为例

围绕完善优课,打造"金课"的理念,推进混合式教学在有机化学实验教学中的应用与实践,以乙醚的制备为例,详细阐述该教学模式的具体实施过程。教学实践说明混合式教学辅以实验的创新设计,不仅可以提高学生课前的自学成效,激发学生学习的探索欲,而且还能促进教师教学水平的提升,提高教学的创新性,可在实验教学中推广。

Content and Antidepressant Effects of Total Flavonoids from Zanthoxylum Pericarpium Residue

[Objectives]To study the content and antidepressant effects of the flavonoids in the Zanthoxylum Pericarpium Residue(ZPR)and to provide a basis for the full utilization of ZPR.[Methods]The method for the assay of total flavonoids in ZPR by UV spectrophotometry was developed with rutin as reference.The total flavonoids were extracted and separated from ZPR.The contents of total flavonoids were quantified in ZPR and its extract.The autonomous activity test,tail suspension test and forced swimming test were conducted in mice,and the levels of malondialdehyde(MDA),superoxide dismutase(SOD)and total antioxidation were detected to evaluate the antidepressant effects of total flavonoids.[Results]The recovery rate of UV spectrophotometry was 98.88%(n=6).The contents of flavonoids in ZPR and its extract were 11.07%and 78.42%,respectively.In the autonomous activity test,compared with the control group,the standing times of mice in the positive drug group was significantly increased(P<0.05),but there was not significant difference among the low-,medium-and high-dose groups of total flavonoids extract(P>0.05),as well as there was no significant difference of the activity times among all groups(P>0.05).In the tail suspension and forced swimming tests,compared with the control group,the immobility time of the high-dose group of total flavonoids extract was significantly reduced(P>0.05),and the serum SOD levels of the low-,medium-and high-dose groups were significantly increased(P<0.05).The MDA levels of the middle-and high-dose groups of total flavonoids were significantly decreased(P<0.05),and the total antioxidant capacity was increased significantly(P<0.05).[Conclusions]The developed UV spectrophotometry can accurately detect the level of total flavonoids in ZPR.ZPR is rich in flavonoids,and has significant antidepressant effects,which may be related to eliminating internal free radicals and inhibiting lipid peroxidation.

Proteomics-based analysis of functional proteins from fermented of compound wheat embryo Chinese medicine

Compound probiotics were used to ferment compound wheat embryo Chinesemedicine(CWECM)at 37°C for a given period,and the fermentation end pointwas determined based on pHvalue.The full spectrumof the proteinswithin the fermentation supernatant was determined by ion mass spectrometry,and then the fermentation was analyzed by proteomics.The difference of functional protein ofCWECMwas analyzed before and after fermentation.Additionally,the changes in flavor of peptides were examined.Our results indicated that when the fermentationwas performed for 96 h,the pH value became stable over time,which it shifted froman initial 3.98±0.04 to a stable 2.78±0.04.Proteomicbased analysis of the fermentation supernatant indicated that the fermentation of the probiotics increased.The amount of functional proteome and protein within the supernatant increased from 60 proteomes and 136 proteins before fermentation to 70 proteomes and 149 proteins post fermentation.These proteins were primarily members of the Ubiquitin and Histone families.These families contain more specific peptides after fermentation,and the coverage was reduced.Analysis of the unique P0C512 protein after fermentation indicated that this protein is an unstable,3Deffect columnar protein.We also found that probiotic fermentation can reduce the proportion of bitter peptideswithin fermentation broth from 47.49%to 36.98%,and the proportion of sweet peptides increased after fermentation from 35.29%to 51.01%.Based on testing,we concluded that fermentation of CWECM by compound probiotics can reduce the pH of the CWECM solution,increase the number of functional proteomes and proteins,improve the taste of CWECM solutions,and improve the therapeutic efficacy of CWECM.

Relationship between severity of trunk decay of Pinus koraiensis and soil properties around roots

The decay rate of standing Korean pine(Pinus koraiensis)in natural forests can be as high as 50%and is likely infl uenced by the soil properties and nutrient and water status of the site.To clarify the relationship between the severity of tree decay and soil properties in order to prevent decay in a natural mixed forest in the Xiaoxing'an Mountains,wood strength of standing trees was nondestructively assessed,and the severity of decay of extracted wood cores was quantified based on differences in mass between two decayed increment cores extracted at breast height and an intact increment core near the decayed ones.Soil samples from the critical root zone(non-rhizosphere)of each tree were analyzed for chemical properties and microbial composition.The abundance of chemical elements(especially total N and K)and the species richness of soil microbes increased as decay severity increased.Fungal number(FN)and actinomycetes number(AN)were related to decay severity(R^(2)=0.504).Bacterial number(BN)was higher than FN or AN,but had a minor effect on tree decay.Path analysis showed BN might indirectly inhibit decay by affecting FN.Decay severity was not significantly correlated with either soil fungal or bacterial diversity.These results suggest that forest managers need to monitor levels of fungi and total N and total K levels to reduce the decay of Korean pine.

Development of Ecological Fishery in Poyang Lake Area

Through in-depth analysis on history and current situations of fishery development in Poyang Lake area,this paper presents location,resource and environment advantages in development of ecological fishery.According to orientation of leading functions,Poyang Lake can be divided into breeding development,capture operation,enhancement protection and ecological rehabilitation functional zones.In accordance with industrial foundation and ecological advantages of cities and counties in Poyang Lake,it determines the reasonable distribution of 8 leading industries:river crabs,shrimps(Procambarus clarkia),eels,Pengze crucian carp,Siniperca chuatsi,Channa argus,Ietalurus Punetaus,and pearl.On the basis of systematically summing up exploration experience,it comes up with the development path"ecology oriented fishery and industrialization oriented ecological fishery"for ecological fishery in Poyang Lake area.It proposes a series of key technological measures,including reducing fertilizer and drugs,increasing output and benefits,low consumption and emission,high quality and safety,and standardization,to realize a benign cycle of"cost saving,benefit increasing,quality improving and low carbon"and the multi-win objective of coordination between ecology,economy and society.

Qualitative Identification and Semi-Quantitative Comparison of Sucrose in Maca (<i>Lepidium meyenii</i>) by Infrared Spectrum Analysis

Objective: In order to establish a method for qualitative identification and semi-quantitative comparison of sucrose in Macas by infrared spectral analysis. Methods: Six Maca samples with three color types and from two producing areas in Yunnan province (China) were collected. Fourier trans-form infrared spectroscopy (FTIR) of raw Maca, ethyl acetate extracts (EtOAc-E), alcohol extracts (EtOH-E) and extracted residues were recorded selectively. Comparative analysis and analysis-through-separation strategies were used to explore the FTIR analytical method for sucrose in Maca. Results: Sucrose was proved to be a component in the Lijiang purple Maca (LPM) sample by comparative analysis of FTIR and second derivative in-frared spectroscopy (SDIR) with sucrose as a reference substance. Relative higher content of sucrose might be responsible for the distinctive absorption character of FTIR from LPM. With the aid of comparative analysis and analysis-through-separation strategies, conclusions could be drawn that all of the six Maca samples in this research contained some sucrose more or less. Furthermore, relative content of sucrose in the LM was higher than those in HM in general. Conclusion: An infrared spectrum analysis method for qualitative identification and semi-quantitative comparison of sucrose in different Maca samples was developed. Compared with other analytical methods, the developed method shows unparalleled charm for its inherent merits of convenient, fast, low cost, visual, efficient et al.

The Exploration of Trimeresurus Divided to Multiple Genera Based on Molecular Systematics

According to the contradictions about classification on Trimeresurus between ＂China＇s Fauna＂ and international database, the rationality about Trimeresurus divided to multiple genera based on molecular systematies was discussed. The genetic distance was calculated by sequencing 12S gene of the original Trimeresurus snakes, including 80 individuals of 33 species ; and the molecular phylogenetie tree was established by taking Hypnale hypnale as the outgroup. The results showed that the topological structures of ME tree and ML tree were basically consistent, and all of the species in the molecular trees were divided into 8 branches; and the difference of T. albolabris between Hainan and other locations is not obvious. The viewpoint that original Trimeresurus genera subdivided into 8 genera was more rational, and new authoritative reference books are expected to be published in China.

基于DA-CycleGAN的化工过程多工况故障诊断方法

化工生产过程中可能会存在着多种运行工况。一方面,当生产工况变化时,故障诊断模型的性能会恶化。另一方面,由于故障是小概率事件,因此在新工况下只能获取到正常运行数据。为解决这些问题,提出一种基于二维循环一致性生成对抗网络(Cycle-Consistent Generative Adversarial Networks,Cycle GAN)的多工况故障诊断方法。该方法首先利用二维Cycle GAN捕获历史工况下各类故障的时空域特征,并将这些特征添加到新工况的正常数据中,用以构建新工况下的伪故障数据集。其次,使用领域自适应方法减少真实故障数据与生成数据间的分布差异,使故障知识更好地迁移到新工况中。利用田纳西-伊斯曼(TE)过程的十二个变工况故障诊断任务对所提算法进行性能测试,实验结果表明,该算法相比于直接利用历史工况下故障数据建模能提高平均故障诊断率3%以上,能有效提高模型在新工况下的故障诊断性能。

Mn-doped LiFePO_(4)@C as a high-performance cathode material for lithium-ion batteries

In this work,LiFe_(1-x)MnxPO_(4)@C(x=0,0.01,0.02,0.03)cathode materials were obtained by a simple co-precipitation method and heat treatment,and the influence of Mn-doped modification on the electrochemical performance of LiFePO_(4)@C cathode materials was investigated.Results show that by doping an appropriate amount of Mn,the cell volume became larger,and the electronic conductivity increased,which improved the Li+diffusion rate and thus its rate capability and cycle performance of Li-ion batteries.Among them,LiFe_(0.98)Mn_(0.02)PO_(4)@C showed superior lithium storage capability;the discharge capacity can reach 150.7 mAh g^(−1)at 0.1 C.The cell could discharge up to 155.9 mAh g^(−1)at 1 C under high temperature at 45°C,which was higher than LiFePO_(4)@C(142 mAh g^(−1))under the same test conditions.The discharge capacity of 1 C at room temperature was 139.9 mAh g^(−1),and the cycle stability was 95.9%after 200 cycles.It showed that it had good rate capability and excellent cycle performance.These results indicate that Mn-doped LFP is a simple and effective strategy for developing high-performance cathode materials.

Depth and Width for Unbounded DG-Modules

This paper introduces the notion of depth with respect to ideals for unbounded DG-modules,and gives a reduction formula and the local nature of this depth.As applications,we provide several bounds of the depth in special cases,and recover and generalize the known results about the depth of complexes.In addition,the width with respect to ideals for unbounded DG-modules is investigated and the depth and width formulas for DG-modules are generalized.