Paclitaxel-induced stress granules increase LINE-1 mRNA stability to promote drug resistance in breast cancer cells

Abnormal expression of long interspersed element-1 (LINE-1) has been implicated in drug resistance, while our previous study showed that chemotherapy drug paclitaxel (PTX) increased LINE-1 level with unknown mechanism. Bioinformatics analysis suggested the regulation of LINE-1 mRNA by drug-induced stress granules (SGs). This study aimed to explore whether and how SGs are involved in drug-induced LINE-1 increase and thereby promotes drug resistance of triple negative breast cancer (TNBC) cells. We demonstrated that SGs increased LINE-1 expression by recruiting and stabilizing LINE-1 mRNA under drug stress, thereby adapting TNBC cells to chemotherapy drugs. Moreover, LINE-1 inhibitor efavirenz (EFV) could inhibit drug-induced SG to destabilize LINE-1. Our study provides the first evidence of the regulation of LINE-1 by SGs that could be an important survival mechanism for cancer cells exposed to chemotherapy drugs. The findings provide a useful clue for developing new chemotherapeutic strategies against TNBCs.     

Higher Dosage of HIFU Treatment May Lead to Higher and Longer Efficacy for Moderate to Severe Perennial Allergic Rhinitis

Objectives: This study was to compare the efficacies and side effects of high intensity focused ultrasound (HIFU) treatment for perennial allergic rhinitis (PAR) with regular and increased dosage.Study design: A prospectively assembled cohort was retrospectively analyzed through visual analogue scale (VAS).Methods: Regular dosage of HIFU treatment was applied to 56 PAR patients in group A. An increased dosage as twice as the regular one was applied to 48 patients in group B. Nasal obstruction, sneezing, rhinorrhea and rhinocnesmus, which were recognized as the four main symptoms of allergic rhinitis (AR), were evaluated before treatment, 3 months after treatment, and 1 year after treatment. The satisfaction of patients was also evaluated at 1 year postoperatively. Biopsy of the inferior turbinate and morphometric analysis were applied to 11 patients in group A and 10 in group B before HIFU treatment and 3 months after treatment.Results: Comparing the AR symptoms before treatment, There is no statistical difference observed between group A and B (p>0.05). The four main symptoms at 3 months and 1 year after treatment were all significantly improved (p<0.01) in both group A and B. The VAS scores of AR symptoms in Group B were lower than those in Group A at the same stage after treatment, especially at 1 year after treatment (p<0.05). Comparing the results at 3 months and 1 year after treatment, a tendency of recurrence of these symptoms was observed statistically in group A (p<0.05), but not in group B (p>0.05). More cases of nasal dryness and perirhinal swelling were found in group B than those in group A (p<0.05), while all side effects were mild and temporary. Patients in group B were more satisfied than those in group A (p=0.0866 >0.05), though not statistically significant. More reduction of the eosinophils, other inflammatory cells, and the submucosal glands was observed after HIFU treatment in group B than that in group A (p<0.05).Conclusions: A proper increment of HIFU dosage may be recommended to meet the needs of more improvement of AR symptoms and less recurrence.     

Constructing Rh–Rh3+ modified Ta2O5@TaON@Ta3N5 with special double n–n mutant heterojunctions for enhanced photocatalytic H2-evolution

A multiple core–shell heterostructure Rh–Rh³⁺ modified Ta₂O₅@TaON@Ta₃N₅ nanophotocatalyst was successfully constructed through nitriding Rh³⁺-doped Ta₂O₅ nanoparticles, which exhibited a much higher carrier separation efficiency about one order of magnitude higher than the Ta₂O₅@Ta₃N₅ precursor, and thus an excellent visible light photocatalytic H₂-evolution activity (83.64 μmol g⁻¹ h⁻¹), much superior to that of Rh anchored Ta₂O₅@TaON (39.41 μmol g⁻¹ h⁻¹), and improved stability due to the residual Rh–O/N in the Ta₃N₅ shell layer. Rh-modifying significantly extended light absorption to the overall visible region. Localized built-in electric fields with hierarchical potential gradients at the multiple interfaces including a Rh/Ta₃N₅ Schottky junction and double n–n Ta₃N₅/TaON/Ta₂O₅ mutant heterojunctions, drove charge carriers to directionally transfer from inside to outside, and efficiently separate. Enhanced photoactivity was ascribed to a synergetic effect of improved light absorption ability, increased carrier separation efficiency, and accelerated surface reaction. A promising strategy of developing excellent Ta₃N₅-based photocatalysts for solar energy conversion is provided by constructing double n–n mutant heterojunctions.

Localized built-in electric fields at multiple hierarchical interfaces facilitate the efficient separation and fast inside-out directional transfer of photogenerated carriers.     

不同碳水化合物肠内营养液对应激性高血糖患者早期血糖水平与预后的影响

目的观察不同的碳水化合物肠内营养液［肠内营养乳剂（TPF-D）和肠内营养混悬液（TPF）］用于早期肠内营养对应激性高血糖患者血糖水平与预后的影响,探讨其作为应激性高血糖患者早期肠内营养制剂的临床可行性。 方法选入2020年6至10月徐州医科大学附属医院急诊ICU收治的合并应激性高血糖的患者为研究对象。根据入排标准,最终71例患者纳入研究,随机数字表法将其分为观察组（35例,鼻饲TPF-D）和对照组（36例,鼻饲TPF）。收集患者一般资料,包括性别、年龄、急性生理与慢性健康状况（APACHE Ⅱ）评分;记录患者第1、3、7天每4小时一次血糖数据,并计算平均血糖值（GLU_AVE）、平均血糖波动幅度（GLU_MAGE）;计算治疗后3、7 d胰岛素应用总量;监测患者第1、7天相关营养指标变化,如总蛋白（TP）、白蛋白（ALB）、前白蛋白（PA）;记录胃肠道并发症（如反流、呕吐、腹泻、腹胀等）、ICU住院时间及28 d病死率。 结果（1）2组性别比例、年龄、APACHE Ⅱ评分比较,差异均无统计学意义（P＞0.05）。（2）2组第1、3、7天GLU_AVE及第1、3天GLU_MAGE比较,差异均无统计学意义（P＞0.05）;观察组第7天GLU_MAGE显著低于对照组,差异有统计学意义［（0.72±0.08）mmol/L vs（1.56±0.10）mmol/L,t=6.22,P=0.02］。（3）观察组治疗3、7 d胰岛素应用总量显著低于对照组,差异均有统计学意义［（60.40±39.80）U vs（102.70±49.60）U,t=0.17,P=0.02;（110.50±43.30）U vs（202.80±56.40）U,t=2.52,P=0.01］。（4）2组第1、7天TP、PA、ALB比较,差异均无统计学意义（P＞0.05）。（5）2组胃肠道并发症、ICU住院时间、28 d病死率比较,差异均无统计学意义（P＞0.05）。 结论应激性高血糖患者早期营养中,TPF-D较TPF能更好地降低血糖变异性,控制血糖波动幅度,并减少临床中胰岛素用量,但不影响预后。     

Dynamic fluorescence lifetime sensing with CMOS single-photon avalanche diode arrays and deep learning processors

Measuring fluorescence lifetimes of fast-moving cells or particles have broad applications in biomedical sciences. This paper presents a dynamic fluorescence lifetime sensing (DFLS) system based on the time-correlated single-photon counting (TCSPC) principle. It integrates a CMOS 192 × 128 single-photon avalanche diode (SPAD) array, offering an enormous photon-counting throughput without pile-up effects. We also proposed a quantized convolutional neural network (QCNN) algorithm and designed a field-programmable gate array embedded processor for fluorescence lifetime determinations. The processor uses a simple architecture, showing unparallel advantages in accuracy, analysis speed, and power consumption. It can resolve fluorescence lifetimes against disturbing noise. We evaluated the DFLS system using fluorescence dyes and fluorophore-tagged microspheres. The system can effectively measure fluorescence lifetimes within a single exposure period of the SPAD sensor, paving the way for portable time-resolved devices and shows potential in various applications.     

Normobaric hypoxia training causes more weight loss than normoxia training after a 4-week residential camp for obese young adults

Background

Intermittent normobaric hypoxia training, an alternative to altitude training for athletes, may be beneficial to treat overweight and obesity. The purpose of this study is to investigate whether normobaric hypoxia training combined with low-caloric diet has the additive effect on weight loss compared with normoxia training in obese young adults.

Methods

Twenty-two subjects (age 17–25 years, body mass index >27.5 kg/m²) were recruited for a 4-week residential camp of weight loss with low caloric intake, and trained at 60–70 % maximal heart rate of aerobics and 40–50 % of maximal strength of training. They were randomly assigned to either a normobaric hypoxia (HT, FiO₂?=?16.4–14.5 %) or normoxia training group (NT, FiO₂?=?21 %), and subjects in HT and NT groups experienced weekly 16-h normoxia and 6-h hypoxia or 22-h normoxia training, respectively. Body composition, resting blood pressure (BP) and brachial-ankle pulse wave velocity (baPWV) were determined before and after the intervention.

Results

Weight loss was found in HT (?6.9 kg or ?7.0 %, p?p?p?<?0.01). Hypoxia training improved systolic BP (?7.6 %) and mean BP (?7.1 %) significantly (p?<?0.05) despite having no effect on baPWV.

Conclusion

Four weeks of normobaric hypoxia residential training with low caloric diet has an additive improvement on weight loss. It seems that normobaric hypoxia training might be a promising method to treat obesity.     

Label‐free molecular probe based on G‐quadruplex and strand displacement for sensitive and selective detection and naked eye discrimination of exon 2 deletion of AIMP2

Exon 2 deletion of aminoacyl tRNA synthetase complex‐interacting multifunctional protein 2 (AIMP2) is a genetic deletion related to various cancers, for instance ovarian and lung cancers. It can be worked as an indicator of cancer for diagnosis of diseases. Here, we developed a label‐free method based on the formation of split G‐quadruplex in the presence of target DNA combined with strand displacement to detect exon 2 deletion of AIMP2 (DE2) sensitively and selectively. This method is easy‐operating and cost‐saving. Moreover, it has observed discrimination of gene deletion from wild‐types by naked eyes. The results demonstrate that this strategy can be further used for the detection of different gene deletions to achieve early diagnosis of diseases and allow better prognosis.     

Traditional uses,phytochemistry, pharmacology and toxicology of Lamiophlomis rotata (Benth.) Kudo: a review

Lamiophlomis rotata (Benth.) Kudo is a herbaceous plant of the family Lamiaceae, subfamily Lamioideae. Approximately, 127 chemical constituents have been isolated and identified from L. rotata, including iridoids, flavonoids, phenylethanoid glycosides, polysaccharides, and organic acids. These chemical constituents have extensive pharmacological properties, which include anti-nociceptive, haemostatic, anti-inflammatory, anti-tumour, immunomodulatory, antioxidant, and cardio-protective activities. Documentation of its historical use in traditional medicine and contemporary phytochemical and pharmacological research indicate that L. rotata has significant potential in therapeutic and health care applications. Both whole extracts and individual chemical components isolated from this plant exhibit a wide range of biological activities that warrant further investigation. These investigations can be assisted by careful review of existing traditional knowledge from diverse cultural backgrounds. A new search for chemical and biological markers and reinforced protection of the germplasm resources of L. rotata are also important to ensure targeted and sustainable use of this medicinal resource. The aim of this review was to provide comprehensive information on the botanical characteristics, traditional uses, ethnopharmacology, chemical and pharmacological properties, toxicity profile, and conservation status of L. rotata, to improve understanding of its mechanisms of action so that novel therapeutic agents may be developed from this plant.

The useful information of Lamiophlomis rotata (Benth.) Kudo was summarized, which provided a basis for the development of new therapeutic drugs for this plant.     

Brain structural correlates of upward social mobility in ethnic minority individuals

Purpose

Perigenual anterior cingulate cortex (pACC) is a neural convergence site for social stress-related risk factors for mental health, including ethnic minority status. Current social status, a strong predictor of mental and somatic health, has been related to gray matter volume in this region, but the effects of social mobility over the lifespan are unknown and may differ in minorities. Recent studies suggest a diminished health return of upward social mobility for ethnic minority individuals, potentially due to sustained stress-associated experiences and subsequent activation of the neural stress response system.

Methods

To address this issue, we studied an ethnic minority sample with strong upward social mobility. In a cross-sectional design, we examined 64 young adult native German and 76 ethnic minority individuals with comparable sociodemographic attributes using whole-brain structural magnetic resonance imaging.

Results

Results showed a significant group-dependent interaction between perceived upward social mobility and pACC gray matter volume, with a significant negative association in the ethnic minority individuals. Post-hoc analysis showed a significant mediation of the relationship between perceived upward social mobility and pACC volume by perceived chronic stress, a variable that was significantly correlated with perceived discrimination in our ethnic minority group.

Conclusion

Our findings extend prior work by pointing to a biological signature of the “allostatic costs” of socioeconomic attainment in socially disadvantaged upwardly mobile individuals in a key neural node implicated in the regulation of stress and negative affect.

     

肝移植术后中期肝脏血流动力学与肝功能异常的关系

目的通过分析肝移植术后中期血流动力学的规律,探讨其与肝功能的关系。方法以2014年2月至2015年10月于青岛大学附属医院进行肝移植手术的56例肝移植受者为研究对象,按肝功能正常与否分为正常组(24例)和异常组(32例)。记录两组的一般资料及肝功能,并应用超声检测其肝移植术前及术后1、30、90 d的肝动脉峰值血流速度(HAP)、门静脉峰值血流速度(PVP)、门静脉灌注量(PVF)等,并计算肝动脉缓冲能力(BC)、校正BC等。对两组间肝脏血流动力学因素与肝功能关系进行单因素和多因素分析,并绘制受试者工作特征(ROC)曲线。结果异常组中移植术后30 d的PVP、PVF明显高于正常组(P=0.014、0.049),正常组中BC及校正BC明显高于异常组(P=0.048、0.011)。多因素分析显示校正BC是其独立危险因素(P=0.047),ROC曲线下面积(AUC)为0.705,灵敏度为0.652,特异度为0.750。结论肝移植术后30 d的PVP、PVF、BC及校正BC可能与肝功能异常有关,其中校正BC可作为诊断及干预肝功能异常的指标之一。