Clinical observation on Aralia echinocauIis Hand Mazz Capsula-2 in knee joint of osteoarthritis

目的  观测刺老苞胶囊-2号临床治疗膝关节骨性关节炎的效果。 方法  将2013～2014年门诊收治的膝关节骨性关节炎患者90例(男50例、女40例)分为：治疗-1组35例（男20例，女15例），治疗-2组20例（男10例，女10例），对照组35例（男20例，女15例）。治疗-1组口服刺老苞胶囊-2号，治疗-2组口服刺老苞胶囊-2号+芬必得胶囊，对照组口服芬必得胶囊。连续服药60d后，观察主要症状缓解情况，并按照膝关节功能评分标准比较各组治疗前后效果。 结果  与对照组（总有效率91.43%）相比，治疗-1组（总有效率85.71%）疗效稍逊，治疗-2组（总有效率95.00%）疗效稍好，但组间差异性均不显著（P＞0.05)。 结论  本实验室制备的刺老苞胶囊-2号对膝关节骨性关节炎有一定的治疗效果，如配合芬必得胶囊共同使用，临床疗效更好。Objective: To observe the effect of Aralia echinocauIis Hand. Mazz capsula-2 on the treatment of knee osteoarthritis．Method: 90 cases of knee osteoarthritis (Male 50 cases / Female 40 cases) were collected in 2013 and 2014, and they were divided into three groups. 35 persons (Male 20 cases / Female 15 cases) in treatment group-1 received Aralia echinocauIis Hand. Mazz capsula-2, 20 persons (Male 10 cases / Female 10 cases) in treatment group-2 received Aralia echinocauIis Hand. Mazz capsula-2 +finbid, 35 persons (Male 20 cases / Female 15 cases) in control group received finbid for 60 days in a course of treatment．Result: Compared with control group (91.43%), treatment group-1 ′s effective rate (85.71%) was lower and treatment group-2′s effective rate (95.00%) was higher, but the difference in different groups was no statistically significant (P＞0.05)．Conclusion: Aralia echinocauIis Hand. Mazz capsula-2 in the treatment of knee osteoarthritis showed good efficacy, joint pain could be shortened．If patients were cured by finbid with Aralia echinocauIis Hand. Mazz capsula-2 together, they would get better clinical curative effect

New insight into smart ocean: how is it different from digital ocean?

Oceans occupy approximately seventy-one percent of the earth’s surface, and vast regions of oceans are virtually unexplored, especially the deep parts where humans have never been. Therefore, it is urgent to understand our oceans from a number of perspectives. In this paper, the concept of Smart Ocean (SO) is constructed from the perspectives of environmental protection, sustainable development of the blue economy and marine disaster prevention and mitigation. First, a double-funnel structure concept model of SO, including ocean observation infrastructure, data, information, application, knowledge and decision support layers, is put forward. Second, the differences between SO and Digital Ocean (DO) are analyzed. Third, taking the Decision Support System for Emergency at Taiwan Strait as an example, a case study, which has assisted in saving more than 200 people, is introduced. Finally, future research agenda is summarized into seven aspects, including new instrumentation and sensor technologies, ocean big data mining and knowledge discovering, prediction, forecast and uncertainty analysis, ocean environment protection technologies and policy, sustainable use of ocean energy and resource, the influence and response to global changes in the ocean, and interdisciplinary collaboration and public service

MixGen: A New Multi-Modal Data Augmentation

Data augmentation is a necessity to enhance data efficiency in deep learning. For vision-language pre-training, data is only augmented either for images or for text in previous works. In this paper, we present MixGen: a joint data augmentation for vision-language representation learning to further improve data efficiency. It generates new image-text pairs with semantic relationships preserved by interpolating images and concatenating text. It's simple, and can be plug-and-played into existing pipelines. We evaluate MixGen on four architectures, including CLIP, ViLT, ALBEF and TCL, across five downstream vision-language tasks to show its versatility and effectiveness. For example, adding MixGen in ALBEF pre-training leads to absolute performance improvements on downstream tasks: image-text retrieval (+6.2% on COCO fine-tuned and +5.3% on Flicker30K zero-shot), visual grounding (+0.9% on RefCOCO+), visual reasoning (+0.9% on NLVR$^{2}$), visual question answering (+0.3% on VQA2.0), and visual entailment (+0.4% on SNLI-VE).Comment: Technical report. First three authors contributed equally. Code are available at https://github.com/amazon-research/mix-generatio

Chlormequat Chloride Inhibits TM3 Leydig Cell Growth via Ferroptosis-Initiated Inflammation

Ferroptosis hallmarked by lipid peroxidation and iron homeostasis imbalance is involved in the occurrence and development of various diseases. The plant growth regulator chlormequat chloride (CCC) can contribute to the causality and exacerbation of reproductive disorders. However, the mechanism by which CCC may cause Leydig cell attenuation remains poorly understood. In this study, TM3 Leydig cells were used to investigate the inhibitory effect of CCC on cell growth and its possible mechanism. The results showed that CCC caused apoptosis, pyroptosis, ferroptosis and necroinflammation in TM3 cells. By comparing the effects of ferroptosis inhibitor Ferrostatin-1 (Fer-1) and pan-Caspase inhibitor Z-VAD-FMK (ZVF) on lipid peroxidation and Caspase-mediated regulated cell death (RCD), we found that Fer-1 was better at rescuing the growth of TM3 cells than ZVF. Although ZVF reduced mitochondrial ROS level and inhibited the activation of Caspase3 and Caspase1, it could not significantly ameliorate lipid peroxidation and the levels of IL-1β and HMGB1 like Fer-1. Therefore, ferroptosis might be a key non apoptotic RCD mode responsible for CCC-driven inflammation, leading to weakened viability and proliferation of TM3 cells. In addition, overexpression of ferritin light chain (FTL) promoted the resistance of TM3 cells to CCC-induced ferroptosis-mediated inflammation and to some extent improved the inhibition of viability and proliferation. Altogether, ferroptosis-initiated inflammation might play a key role in CCC-impaired TM3 cell growth

High-space-coverage lake level change data sets on the Tibetan Plateau from 2002 to 2021 using multiple altimeter data

The Qinghai Tibet region, known as the Roof of the World and the Water Tower of Asia, has the largest number of lakes in the world, and because of its high altitude and the near absence of disturbance by human activity, the Tibetan plateau has long been a significant place to study global climate change. Hydrological stations cannot be easily set up in this area, and the in-situ gauge data are not always publicly accessible. Satellite radar altimetry has become a very important alternative to in-situ observations as a data source. Estimation of lake water levels with a given radar altimeter is often limited by temporal and spatial coverage, and therefore multi-altimeter data are used to monitor lake levels. Restricted by the accuracy of waveform processing and the intervals period between different altimetry missions, the accuracy and the sampling frequency of the water level series are low. By processing and merging 8 different altimetry missions, the developed data set gives the water level changes for 364 lakes (larger than 10 km2) in Tibetan Plateau from 2002 to 2021. The period of lake level change series with high accuracy can be much longer in many lakes. This data set and associated approaches are valuable for calculating the lake storage changes, trend analyses of lake level, short-term monitoring of lake overflow, flooding disasters on the Tibetan Plateau, and the relationships between the lake ecosystem change and water resources change

Optimization design of adjustment mechanism for nanoradian flexible angular displacement

BackgroundThere is increased demand for high spatial resolution in domestic and international nano-imaging experimental stations utilizing synchrotron radiation. Nano or nanoradian level positioning accuracy and stability are necessary for focusing mirrors or monochromators on the beamlines.PurposeThis study aims to design and optimize a redundant parallel flexible hinge rotating device to meet this demand.MethodsFirst of all, the kinematics of the flexible mechanism were initially analyzed, and the virtual displacement principle was employed to derive the overall static rotational stiffness of the mechanism. Then, the characteristics of the mechanism, as well as the impact of hinge parameters on stiffness, were investigated. Subsequently, the dynamic model of the mechanism was built by employing the Lagrange equation, and the natural frequency in the motion direction was deduced. Finally, an optimization model was developed for the static and dynamic dual purpose mechanism design, solved through a genetic algorithm accounting for nonlinear constraints. In addition, the first four resonance frequencies and vibration modes of the flexible mechanism were examined using a finite element method for modal analysis followed by the creation and assembly of a high-precision flexible hinge mechanism along with a rotary adjustment device for experimental testing.ResultsTest results indicate that the flexible angular displacement adjustment mechanism achieves a rotation angle of 0.668° and bidirectional repeatability of ±8.91 nrad during fine-tuning. In addition, the angle resolution of 15 nrad and stability of 2.72 nrad (root mean square value) are achieved over a 30 min test in the frequency range of 1~500 Hz. The first natural frequency of the mechanism is approximately 295 Hz, which aligns with the theoretical calculations and finite element analysis results.ConclusionsThe effectiveness and reliability of the optimized flexible mechanism in achieving nanoradian level high-precision angular displacement adjustment is confirmed by this study

Insights into Chain Elongation Mechanisms of Weak Electric-Field-Stimulated Continuous Caproate Biosynthesis:Key Enzymes, Specific Species Functions, and Microbial Collaboration

Chain elongation (CE) technology can recover high-value biochemicals such as caproate, contributing to the realization of carbon neutrality. Electro-assisted fermentation shows extraordinary potential to enhance microbial activity in anaerobic fermentation systems. However, little is known of the effects of key functional genes of enzymes, specific species functions, and microbial collaboration on caproate biosynthesis in the continuously fed expanded granular sludge bed (EGSB) reactor with mixed culture under a weak electric field. In this study, caproate production was enhanced by 21% with 0.05 V electric field introduction in the CE bioreactor continuously operated for 150 days. Mechanism investigation revealed the abundance of functional genes involved in converting substrates to key intermediates (acetyl CoA and malonyl CoA) and in the fatty acid biosynthesis pathway (FAB), and the activities of transmembrane transport and energy metabolism were upregulated. Ruminococcaceae_bacterium played the most significant role in enhancing caproate biosynthesis with electric field introduction. Some essential functional genes were undetected within Ruminococcaceae_bacterium, which implied that harmonious microbial collaboration existed to supplement the lacking functional genes to complete CE processes. Firmicutes_bacterium, Pseudomonas_aeruginosa, Caproiciproducens_sp._NJN-50 and Candidatus_Neoanaerotignum_tabaqchaliae played complementary and collaborative roles in constructing the  microbial collaboration mechanisms in the CE process with the electric field. This study offered a deep understanding of the CE mechanisms in the mixed-culture continuously fed reactor and unveiled the respective roles of different species and the microbial interaction and collaboration mechanisms with weak electric field stimulation and provided a promising strategy for enhancing caproate biosynthesis

FTO-mediated m6A modification alleviates autoimmune uveitis by regulating microglia phenotypes via the GPC4/TLR4/NF-κB signaling axis

Uveitis, a vision-threatening inflammatory disease worldwide, is closely related to resident microglia. Retinal microglia are the main immune effector cells with strong plasticity, but their role in uveitis remains unclear. N6-methyladenosine (m6A) modification has been proven to be involved in the immune response. Therefore, we in this work aimed to identify the potentially crucial m6A regulators of microglia in uveitis. Through the single-cell sequencing (scRNA-seq) analysis and experimental verification, we found a significant decrease in the expression of fat mass and obesity-associated protein (FTO) in retinal microglia of uveitis mice and human microglia clone 3 (HMC3) cells with inflammation. Additionally, FTO knockdown was found to aggravate the secretion of inflammatory factors and the mobility/chemotaxis of microglia. Mechanistically, the RNA-seq data and rescue experiments showed that glypican 4 (GPC4) was the target of FTO, which regulated microglial inflammation mediated by the TLR4/NF-κB pathway. Moreover, RNA stability assays indicated that GPC4 upregulation was mainly regulated by the downregulation of the m6A “reader” YTH domain family protein 3 (YTHDF3). Finally, the FTO inhibitor FB23-2 further exacerbated experimental autoimmune uveitis (EAU) inflammation by promoting the GPC4/TLR4/NF-κB signaling axis, and this could be attenuated by the TLR4 inhibitor TAK-242. Collectively, a decreased FTO could facilitate microglial inflammation in EAU, suggesting that the restoration or activation of FTO function may be a potential therapeutic strategy for uveitis

Chlorocholine chloride exposure induced spermatogenic dysfunction via iron overload caused by AhR/PERK axis-dependent ferritinophagy activation

Chlorocholine chloride (CCC) is a plant growth regulator used worldwide that is detectable in cereals, fruits and animal products. The health effects of CCC exposure have raised public concern. Our previous research showed that CCC exposure decreased testosterone synthesis in pubertal rats. However, little is known about whether and how pubertal CCC exposure impacts spermatogenesis. In this study, we used BALB/c mice and spermatogonia-derived GC-1 cells to examine CCC-induced spermatogenic dysfunction. In vivo, pubertal CCC exposure led to decreased testicular weight, decreased testicular germ cells and poor sperm quality. This effect worsened after cessation of CCC exposure for the next 30 days. RNA-seq and western blot analysis revealed that CCC induced aryl hydrocarbon receptor (AhR) signaling, endoplasmic reticulum stress (ERS) and ferritinophagy. Increased iron content and lipid peroxidation levels were also observed in CCC-treated testes. In vitro, it was identified that iron overload mediated by enhanced ferritinophagy occurred in CCC-treated GC-1 cells, which might be attributed to the PERK pathway in ERS. Further, for the first time, our study elucidated the involvement of AhR in CCC-induced iron overload, which aggravated testicular oxidative damage via lipid peroxidation. Considering the adverse impact of CCC exposure on rodents, supportive evidence from GC-1 cells, and the critical importance of spermatogenesis on male development, the effects of CCC on the male reproduction warrant increased attention

The preparation and relative bioavailability of an artemisin in self-emulsifying drug delivery system

AbstractThe aim of this study is to demonstrate a method for improving the solubility and relative bioavailability of artemisinin using a self-emulsifying drug delivery system (SEDDS). The self-emulsifying drug load, solubility, and emulsifying time were used as the evaluation indices, based on a solubility test and a ternary phase diagram. Optimal Mixture Design in Design-Expert software was used to optimize the prescription of the artemisinin SEDDS. By determining the water distribution coefficient in vitro, combined with the drug concentration–time curve in vivo, a comparison was made of the relative oral bioavailability of the artemisinin SEDDS and the crude drug. The optimal prescription ratio of oleic acid polyethylene glycol glyceride, polyoxyethylene hydrogenated castor oil, and diethylene glycol monoethyl ether in the artemisinin SEDDS was 0.5:0.2:0.3 (wt/wt/wt), with a drug loading capacity of 41.556 mg/g, a solubility of 1.997 mg/mL, and a self-emulsification time of 214 s. The optimal prescription was transparent, slightly yellow, and oil-like. The average loading capacity of artemisinin was 41.912 mg/g, the emulsification time was 231 s, the average particle size was 128.0 nm, the average Zeta potential was –4.29 mV, and the solubility of artemisinin SEDDS in water was 1.997 mg mL–1. It is 33.85 times of the solubility of artemisinin in water, which achieves the purpose of increasing the solubility of artemisinin. The comparison of the oil/water distribution coefficient of the artemisinin SEDDS with that of the crude drug in vitro showed that SEDDS could improve the permeability of artemisinin and promote the absorption in vivo, and the relative bioavailability of the SEDDS agent was at least 1.47 times higher than that of the crude drug. The artemisinin SEDDS could significantly improve the solubility and relative bioavailability of artemisinin