Real-Time Dynamic Intelligent Image Recognition and Tracking System for Rockfall Disasters.

Taiwan, frequently affected by extreme weather causing phenomena such as earthquakes and typhoons, faces a high incidence of rockfall disasters due to its largely mountainous terrain. These disasters have led to numerous casualties, government compensation cases, and significant transportation safety impacts. According to the National Science and Technology Center for Disaster Reduction records from 2010 to 2022, 421 out of 866 soil and rock disasters occurred in eastern Taiwan, causing traffic disruptions due to rockfalls. Since traditional sensors of disaster detectors only record changes after a rockfall, there is no system in place to detect rockfalls as they occur. To combat this, a rockfall detection and tracking system using deep learning and image processing technology was developed. This system includes a real-time image tracking and recognition system that integrates YOLO and image processing technology. It was trained on a self-collected dataset of 2490 high-resolution RGB images. The system's performance was evaluated on 30 videos featuring various rockfall scenarios. It achieved a mean Average Precision (mAP50) of 0.845 and mAP50-95 of 0.41, with a processing time of 125 ms. Tested on advanced hardware, the system proves effective in quickly tracking and identifying hazardous rockfalls, offering a significant advancement in disaster management and prevention.

Targeting Ca2+-dependent pathways to promote corneal epithelial wound healing induced by CISD2 deficiency.

Chronic epithelial defects of the cornea, which are usually associated with severe dry eye disease, diabetes mellitus, chemical injuries or neurotrophic keratitis, as well as aging, are an unmet clinical need. CDGSH Iron Sulfur Domain 2 (CISD2) is the causative gene for Wolfram syndrome 2 (WFS2; MIM 604928). CISD2 protein is significantly decreased in the corneal epithelium of patients with various corneal epithelial diseases. Here we summarize the most updated publications and discuss the central role of CISD2 in corneal repair, as well as providing new results describing how targeting Ca2+-dependent pathways can improve corneal epithelial regeneration. This review mainly focuses on the following topics. Firstly, an overview of the cornea and of corneal epithelial wound healing. The key players involved in this process, such as Ca2+, various growth factors/cytokines, extracellular matrix remodeling, focal adhesions and proteinases, are briefly discussed. Secondly, it is well known that CISD2 plays an essential role in corneal epithelial regeneration via the maintenance of intracellular Ca2+ homeostasis. CISD2 deficiency dysregulates cytosolic Ca2+, impairs cell proliferation and migration, decreases mitochondrial function and increases oxidative stress. As a consequence, these abnormalities bring about poor epithelial wound healing and this, in turn, will lead to persistent corneal regeneration and limbal progenitor cell exhaustion. Thirdly, CISD2 deficiency induces three distinct Ca2+-dependent pathways, namely the calcineurin, CaMKII and PKCα signaling pathways. Intriguingly, inhibition of each of the Ca2+-dependent pathways seems to reverse cytosolic Ca2+ dysregulation and restore cell migration during corneal wound healing. Notably, cyclosporin, an inhibitor of calcineurin, appears to have a dual effect on both inflammatory and corneal epithelial cells. Finally, corneal transcriptomic analyses have revealed that there are six major functional groupings of differential expression genes when CISD2 deficiency is present: (1) inflammation and cell death; (2) cell proliferation, migration and differentiation; (3) cell adhesion, junction and interaction; (4) Ca2+ homeostasis; (5) wound healing and extracellular matrix; and (6) oxidative stress and aging. This review highlights the importance of CISD2 in corneal epithelial regeneration and identifies the potential of repurposing venerable FDA-approved drugs that target Ca2+-dependent pathways for new uses, namely treating chronic epithelial defects of the cornea.

Electrical Sympathetic Neuromodulation Protects Bone Marrow Niche and Drives Hematopoietic Regeneration during Chemotherapy.

The sympathetic nervous system (SNS) of the bone marrow regulates the regeneration and mobilization of hematopoietic stem cells. Chemotherapy can damage bone marrow SNS, which impairs hematopoietic regeneration and aggravates hematologic toxicities. This leads to long-term bone marrow niche damage and increases mortality in patients undergoing chemotherapy. Electrical neuromodulation has been used to improve functional recovery after peripheral nerve injury. This study demonstrates that electrical sympathetic neuromodulation (ESN) of bone marrow can protect the bone marrow niche from chemotherapy-induced injury. Using carboplatin-treated rats, the SNS via the sciatic nerve innervating the femoral marrow with the effective protocol for bone marrow sympathetic activation is electrically stimulated. ESN can mediate several hematopoietic stem cells maintenance factors and promote hematopoietic regeneration after chemotherapy. It also activates adrenergic signals and reduces the release of pro-inflammatory cytokines, particularly interleukin-1 ß, which contribute to chemotherapy-related nerve injury. Consequently, the severity of chemotherapy-related leukopenia, thrombocytopenia, and mortality can be reduced by ESN. As a result, in contrast to current drug-based treatment, such as granulocyte colony-stimulating factor, ESN can be a disruptive adjuvant treatment by protecting and modulating bone marrow function to reduce hematologic toxicity during chemotherapy.

A study of green roof and impact on the temperature of buildings using integrated IoT system.

With the rise of environmental consciousness and the evolution of circular cities, the Internet of things (IoT) has been combined with the concept of circular economies to promote the effective control of renewable energy and resources. In this study, a comprehensive IoT system containing front-end device applications, network layer innovations, and cloud platform integrations was used in civil engineering applications. This IoT architecture is presented as a development basis for constructing modular automatic monitoring devices and integrating circular city concepts with the IoT. According to the concept of circular city, green circulation and energy use are systematically integrated and called "green energy". In addition, the green energy system can be divided into above-ground and underground. The above-ground part uses green roofs and solar panels for research and discussion. The composite solar green roofs of the two are called green roofs, and the comparison of their benefits is discussed on the spot. Narrowband IoT (NB-IoT) technologies were used in this study. The advantages of the developed system were analyzed using measured pH values, air temperatures, soil temperatures, and humidity. The results of this study indicate that constructing a green energy roof can decrease indoor temperatures by 1.5 °C and solar module temperatures by 1.6 °C while increasing power generation; thus, green energy roofs are suitable for tropical regions.

Applying an Integrated System of Cloud Management and Wireless Sensing Network to Green Smart Environments-Green Energy Monitoring on Campus.

With increasing urbanization, the application of Internet of things (IoT) technology to city governance has become a trend in architecture, transportation, and healthcare management, making IoT applicable in various domains. This study used IoT to inspect green construction and adopted a front-end sensing system, middle-end wireless transmission, and a back-end multifunctional system structure with cloud management. It integrated civil and electrical engineering to develop environmental monitoring technology and proposed a management information system for the implementation of green engineering. This study collected physical "measurements" of the greening environment on a campus. Ambient temperature and humidity were analyzed to explore the greening and energy-saving benefits of a green roof, a pervious road, and a photovoltaic roof. When the ambient temperature was below 25 °C, the solar panels had an insulation effect on the roof of the building during both 4:00−5:00 and 12:00−13:00, with an optimal insulation effect of 2.45 °C. When the ambient temperature was above 25 °C, the panels had a cooling effect on the roof of the building, whether during 4:00−5:00 or 12:00−13:00, with an optimal cooling effect of 5.77 °C. During the lower temperature period (4:00−5:00), the ecological terrace had an insulation effect on the space beneath, with an effect of approximately 1−3 °C and a mean insulation of 1.95 °C. During the higher temperature period (12:00−13:00), it presented a cooling effect on the space beneath, with an effect of approximately 0.5−9 °C and a mean cooling temperature of 5.16 °C. The cooling effect of the three greening areas on air and ground temperature decreased in the following order: pervious road > photovoltaic roof > ecological terrace.

Discovery of Potential Neuroprotective Agents against Paclitaxel-Induced Peripheral Neuropathy.

Chemotherapy-induced neurotoxicity is a common adverse effect of cancer treatment. No medication has been shown to be effective in the prevention or treatment of chemotherapy-induced neurotoxicity. Using minoxidil as an initial template for structural modifications in conjunction with an in vitro neurite outgrowth assay, an image-based high-content screening platform, and mouse behavior models, an effective neuroprotective agent CN016 was discovered. Our results showed that CN016 could inhibit paclitaxel-induced inflammatory responses and infiltration of immune cells into sensory neurons significantly. Thus, the suppression of proinflammatory factors elucidates, in part, the mechanism of action of CN016 on alleviating paclitaxel-induced peripheral neuropathy. Based on excellent efficacy in improving behavioral functions, high safety profiles (MTD > 500 mg/kg), and a large therapeutic window (MTD/MED > 50) in mice, CN016 might have great potential to become a peripherally neuroprotective agent to prevent neurotoxicity caused by chemotherapeutics as typified by paclitaxel.

Cisd2 plays an essential role in corneal epithelial regeneration.

BACKGROUND: Age-related changes affecting the ocular surface cause vision loss in the elderly. Cisd2 deficiency drives premature aging in mice as well as resulting in various ocular surface abnormalities. Here we investigate the role of CISD2 in corneal health and disease. METHODS: We studied the molecular mechanism underlying the ocular phenotypes brought about by Cisd2 deficiency using both Cisd2 knockout (KO) mice and a human corneal epithelial cell (HCEC) cell line carrying a CRISPR-mediated CISD2KO background. We also develop a potential therapeutic strategy that targets the Ca2+ signaling pathway, which has been found to be dysregulated in the corneal epithelium of subjects with ocular surface disease in order to extend the mechanistic findings into a translational application. FINDINGS: Firstly, in patients with corneal epithelial disease, CISD2 is down-regulated in their corneal epithelial cells. Secondly, using mouse cornea, Cisd2 deficiency causes a cycle of chronic injury and persistent repair resulting in exhaustion of the limbal progenitor cells. Thirdly, in human corneal epithelial cells, CISD2 deficiency disrupts intracellular Ca2+ homeostasis, impairing mitochondrial function, thereby retarding corneal repair. Fourthly, cyclosporine A and EDTA facilitate corneal epithelial wound healing in Cisd2 knockout mice. Finally, cyclosporine A treatment restores corneal epithelial erosion in patients with dry eye disease, which affects the ocular surface. INTERPRETATION: These findings reveal that Cisd2 plays an essential role in the cornea and that Ca2+ signaling pathways are potential targets for developing therapeutics of corneal epithelial diseases. FUNDING: This study was supported by the Ministry of Science and Technology (MOST) and Chang Gung Medical Research Foundation, Taiwan.

Green Smart Campus Monitoring and Detection Using LoRa.

Along with the rapid development of sensing systems and wireless transmission technology, the scope of application of the IoT has substantially increased, and research and innovation that integrate artificial intelligence. This study integrated civil engineering and electrical engineering to establish a universal and modularized long-term sensing system. Aiming at positive construction in civil engineering, the campus of National Taipei University of Technology was used as the experimental site as a green campus. This paper focused on the cooling effect of the green roof and the temperature difference of the solar panel to effectively isolate the direct sunlight on the roof of the building. To achieve long-term monitoring, energy consumption must be minimized. Considering that the distance between sensor nodes in the experimental site was over dozens of feet, LoRa transmission technology was selected for data transmission. LoRa only consumes a small amount of energy during data transmission, and it can freely switch between work modes, achieving optimal power utilization efficiency. The greening-related research results indicated that the shade from solar panels on the rooftop could effectively reduce the temperature increase caused by direct sunlight on concrete surfaces. The temperature reduction effect was positively correlated with whether the solar panels provided shade. After 1 week of monitoring, we observed that having plants on the rooftop for greening negatively correlated with temperature reduction efficiency. Permeable pavement on the ground was positively correlated with temperature reduction efficiency. However, its temperature reduction efficiency was inferior to that of solar panel shading. The temperature difference between high-rise buildings and the ground was approximately 1-2 °C. At the same elevation, the temperature difference between buildings with and without greening was approximately 0.8 °C. Regarding the sensing system designed for this site, both hardware and software could be flexibly set according to the research purposes, precision requirements of the sites, and the measurement scope, thereby enabling their application in more fields.

Production of Trans-Cinnamic Acid by Immobilization of the Bambusa oldhamii BoPAL1 and BoPAL2 Phenylalanine Ammonia-Lyases on Electrospun Nanofibers.

Phenylalanine ammonia-lyase (PAL) catalyzes the nonoxidative deamination of phenylalanine to yield trans-cinnamic acid and ammonia. Recombinant Bambusa oldhamii BoPAL1/2 proteins were immobilized onto electrospun nanofibers by dextran polyaldehyde as a cross-linking agent. A central composite design (CCD)-response surface methodology (RSM) was utilized to optimize the electrospinning parameters. Escherichia coli expressed eBoPAL2 exhibited the highest catalytic efficiency among four enzymes. The optimum conditions for fabricating nanofibers were determined as follows: flow rate of 0.10 mL/h, voltage of 13.8 kV, and distance of 13 cm. The response surface models were used to obtain the smaller the fiber diameters as well as the highest PAL activity in the enzyme immobilization. Compared with free BoPALs, immobilized BoPALs can be reused for at least 6 consecutive cycles. The remained activity of the immobilized BoPAL proteins after storage at 4 °C for 30 days were between 75 and 83%. In addition, the tolerance against denaturants of the immobilized BoPAL proteins were significantly enhanced. As a result, the dextran polyaldehyde natural cross-linking agent can effectively replace traditional chemical cross-linking agents for the immobilization of the BoPAL enzymes. The PAL/nylon 6/polyvinyl alcohol (PVA)/chitosan (CS) nanofibers made are extremely stable and are practical for industrial applications in the future.

Targeting lysosomal cysteine protease cathepsin S reveals immunomodulatory therapeutic strategy for oxaliplatin-induced peripheral neuropathy.

Rationale: Oxaliplatin-induced peripheral neuropathy (OIPN) is a common adverse effect that causes delayed treatment and poor prognosis among colorectal cancer (CRC) patients. However, its mechanism remains elusive, and no effective treatment is available. Methods: We employed a prospective cohort study of adult patients with pathologically confirmed stage III CRC receiving adjuvant chemotherapy with an oxaliplatin-based regimen for investigating OIPN. To further validate the clinical manifestations and identify a potential therapeutic strategy, animal models, and in vitro studies on the mechanism of OIPN were applied. Results: Our work found that (1) consistent with clinical findings, OIPN was observed in animal models. Targeting the enzymatic activity of cathepsin S (CTSS) by pharmacological blockade and gene deficiency strategy alleviates the manifestations of OIPN. (2) Oxaliplatin treatment increases CTSS expression by enhancing cytosol translocation of interferon response factor 1 (IRF1), which then facilitates STIM-dependent store-operated Ca2+ entry homeostasis. (3) The cytokine array demonstrated an increase in anti-inflammatory cytokines and suppression of proinflammatory cytokines in mice treated with RJW-58. (4) Mechanistically, inhibiting CTSS facilitated olfactory receptors transcription factor 1 release from P300/CBP binding, which enhanced binding to the interleukin-10 (IL-10) promoter region, driving IL-10 downstream signaling pathway. (5) Serum CTSS expression is increased in CRC patients with oxaliplatin-induced neurotoxicity. Conclusions: We highlighted the critical role of CTSS in OIPN, which provides a therapeutic strategy for the common adverse side effects of oxaliplatin.

The facilitating effect of MK-801 on inhibitory avoidance memory via mTOR signaling in the mouse hippocampus.

Despite the widespread belief that MK-801 induces memory deficits associated with dementia and schizophrenia in animal models, data regarding the impairing effect of MK-801 on aversive memory have been inconclusive. In this study, we investigated the effect of MK-801 on multiple memory stages of the inhibitory avoidance task, as well as its underlying signaling mechanism in the mouse hippocampus. We successfully replicated a previous finding suggesting that systemic injection of MK-801 impaired memory acquisition, but we observed that an intrahippocampal infusion of MK-801 facilitated the same memory process. We also found that both systemic and intrahippocampal administration of MK-801 facilitated memory consolidation and memory retrieval of the inhibitory avoidance task. We demonstrated that MK-801-induced increases in shock sensitivity and locomotor activity in the pre-training regimen confounded the detrimental effect of MK-801 on memory acquisition, thereby reconciling the inconsistent results in previous studies. In addition, the memory-facilitating effect of MK-801 was found to be dependent on drug dose and shock intensity. We next showed that MK-801 induced a fast-onset increase in the extent of mammalian target of rapamycin (mTOR) phosphorylation in the hippocampus. Finally, we observed that rapamycin, an mTOR inhibitor, blocked both the MK-801-induced increases in phosphorylated mTOR and the facilitating effect of MK-801 on memory consolidation. These results indicate that hippocampal mTOR signaling mediates the facilitating effect of MK-801 on memory consolidation of the inhibitory avoidance task. These findings further imply that MK-801 indeed functions as a memory enhancer and that mTOR signaling serves as a therapeutic target for memory disorders.

Targeting interleukin-20 alleviates paclitaxel-induced peripheral neuropathy.

The role of immune mediators, including proinflammatory cytokines in chemotherapy-induced peripheral neuropathy (CIPN), remains unclear. Here, we studied the contribution of interleukin-20 (IL-20) to the development of paclitaxel-induced peripheral neuropathy. Increased serum levels of IL-20 in cancer patients with chemotherapy were accompanied by increased CIPN risk. In mouse models, proinflammatory IL-20 levels in serum and dorsal root ganglia fluctuated with paclitaxel treatment. Blocking IL-20 with the neutralizing antibody or genetic deletion of its receptors prevented CIPN, alleviated peripheral nerve damage, and dampened inflammatory responses, including macrophage infiltration and cytokine release. Mechanistically, paclitaxel upregulated IL-20 through dysregulated Ca homeostasis, which augmented chemotherapy-induced neurotoxicity. Importantly, IL-20 suppression did not alter paclitaxel efficacy on cancer treatment both in vitro and in vivo. Together, targeting IL-20 ameliorates paclitaxel-induced peripheral neuropathy by suppressing neuroinflammation and restoring Ca homeostasis. Therefore, the anti-IL-20 monoclonal antibody is a promising therapeutic for the prevention and treatment of paclitaxel-induced neuropathy.

Efficacy of green onion root extract in cosmetics and skin care products / Eficácia do extrato de raiz de cebola verde em cosméticos e produtos de cuidado da pele

In this study, leftover roots of Sansing green onions grown without toxic chemicals in Sansing Township, Ilan County, Taiwan were used as a raw material of skincare products. The raw material was extracted from the green onion roots by ultrasound in a low-temperature, safe and pollution-free environment. We hope to develop cleansers and other facial care products made of this natural, environmentally friendly, safe and affordable raw material so that people with sensitive skin can also use these products. We also hope that this study can contribute to circular economy and achieve the goal of green innovation by recycling the leftover roots. In terms of anti-oxidation, the DPPH free radical scavenging ability of 2.5 mg/mL green onion root extract was equivalent to 98% of that of 1 mg/mL BHT; the Fe2+ chelating ability was equivalent to 87.0% of that of 0.02 mg/mL EDTA; the superoxide anions scavenging ability of 2.5 mg/mL green onion root extract was equivalent to 84.2% of that of 1 mg/mL BHT and 80.4% of that of 0.05 mg/mL vitamin C. With respect to melanin synthesis inhibition, the green onion root extract's ability to inhibit dopachrome, the intermediate product of melanin, was positively correlated to its concentration, i.e., the higher the concentration of the green onion root extract, the better the inhibition ability. The IC50 of green onion root extract was 1.83 mg/mL, while, for comparison, the IC50 of vitamin C was 0.62 mg/mL. Furthermore, according to the cell survival assay, no obvious cytotoxic effect was found with the increase in the concentration of the green onion root extract. The whitening effect improved after 30 days of test. The improvement rate was 5.6% for 2.5 mg/mL green onion root extract, 3.1% for 1.25 mg/mL extract, and 1.7% for 0.625 mg/mL extract. The moisture retention also improved after 30 days of test. The moisture retention improvement rate was 22.7% for 2.5 mg/mL green onion root extract, 21.6% for 1.25 mg/mL extract, and 15.4% for 0.625 mg/mL extract. Based on the experiments, the green onion root extract obtained from ultrasound not only did not cause skin allergy and irritation but also showed anti-aging, melanin synthesis inhibition, whitening and moisture retention effects. The results showed that the green onion root extract can improve the moisture retention and whitening effect of the mask.

Neste estudo, restos de raízes de cebolinhas Sansing, cultivadas sem produtos químicos tóxicos no município de Sansing, Condado de Ilan, Taiwan, foram utilizadas como matéria-prima de produtos para a pele. A matéria-prima foi extraída das raízes de cebolinha por ultrassom em um ambiente de baixa temperatura, seguro e livre de poluição. Esperamos desenvolver produtos de limpeza e outros produtos para cuidados faciais produzidos com essa matéria-prima natural, ecologicamente correta, segura e acessível, para Improvement rate (%) Moisture retention Whitening effect 7.65 1.29 que pessoas com pele sensível também possam usar esses produtos. Também esperamos que este estudo possa contribuir para a economia circular e alcançar o objetivo da inovação ecológica, reciclando restos das raízes. Em termos de anti-oxidação, a capacidade de sequestro do radical livre DPPH de 2,5 mg/mL de extrato de raiz de cebolinha foi equivalente a 98% de 1 mg/mL de BHT; a capacidade quelante do Fe2+ foi equivalente a87,0% de 0,02 mg/mL de EDTA; a capacidade de sequestro de ânions superóxidos de 2,5 mg/mL de extrato de raiz de cebolinha foi equivalente a 84,2% de 1 mg/mL BHT e 80,4% de 0,05 mg/mL de vitamina C. No que diz respeito à inibição da síntese de melanina, a capacidade do extrato de raiz de cebolinha de inibir o dopacrômio, o metabolito intermediário de melanina, foi positivamente correlacionada com a sua concentração, ou seja, quanto maior a concentração do extrato de raiz de cebolinha, maior a capacidade de inibição. O IC50 de extrato de raiz de cebolinha foi de 1,83 mg/mL, enquanto que, por comparação, o IC50 de vitamina C foi de 0,62mg/mL. Além disso, de acordo com o ensaio de sobrevivência celular, nenhum efeito citotóxico foi observado com o aumento da concentração do extrato de raiz de cebolinha. O efeito de branqueamento melhora após 30 dias de ensaio. A melhoria foi de 5,6% para 2,5 mg/mL de extrato de raiz de cebolinha, 3,1% para 1,25 mg/mL de extrato e 1,7% para 0,625 mg/mL de extrato. A retenção de umidade também melhorou depois de 30 dias de teste. A taxa de melhoria de retenção de umidade foi de 22,7% para 2,5 mg/mL de extrato de raiz de cebolinha, 21,6% para 1,25 mg/mL de extrato, e 15,4% para 0,625 mg/mL de extrato.Com base nas experiências efetuadas, o extrato de raiz de cebolinha obtida por ultrassom não só não causa alergia nem irritação da pele, mas também demonstrou atividade anti-envelhecimento, inibição da síntese de melanina, capacidade de branqueamento e retenção de umidade. Os resultados mostraram que o extrato de raiz de cebolinha pode melhorar a retenção de umidade e efeito de branqueamento da máscara.

Store-Operated Ca2+ Entry in Tumor Progression: From Molecular Mechanisms to Clinical Implications.

The remodeling of Ca2+ homeostasis has been implicated as a critical event in driving malignant phenotypes, such as tumor cell proliferation, motility, and metastasis. Store-operated Ca2+ entry (SOCE) that is elicited by the depletion of the endoplasmic reticulum (ER) Ca2+ stores constitutes the major Ca2+ influx pathways in most nonexcitable cells. Functional coupling between the plasma membrane Orai channels and ER Ca2+-sensing STIM proteins regulates SOCE activation. Previous studies in the human breast, cervical, and other cancer types have shown the functional significance of STIM/Orai-dependent Ca2+ signals in cancer development and progression. This article reviews the information on the regulatory mechanisms of STIM- and Orai-dependent SOCE pathways in the malignant characteristics of cancer, such as proliferation, resistance, migration, invasion, and metastasis. The recent investigations focusing on the emerging importance of SOCE in the cells of the tumor microenvironment, such as tumor angiogenesis and antitumor immunity, are also reviewed. The clinical implications as cancer therapeutics are discussed.

The distinct role of STIM1 and STIM2 in the regulation of store-operated Ca2+ entry and cellular function.

Stromal interaction molecules STIM1 and STIM2 are endoplasmic reticulum (ER) Ca2+ sensors that initiate store-operated Ca 2+ entry (SOCE). The roles of STIM1-mediated SOCE in cancer biology have been highlighted in different types of cancer, but that of STIM2 is unknown. By the model of cervical cancer, here we focus on the cooperative regulation of SOCE by STIM proteins and their distinct roles in cellular function. Immunofluorescent stainings of surgical specimens of cervical cancer show that STIM1 and STIM2 are abundant in tumor tissues, but STIM1 is the major ER Ca 2+ sensor identified in the invasive front of cancer tissues. STIM1 or STIM2 overexpression in cervical cancer SiHa cells induces an upregulated SOCE. Regarding cellular function, STIM1 and STIM2 are necessary for cell proliferation, whereas STIM1 is the dominant ER Ca 2+ sensor involved in cell migration. During SOCE, STIM1 is aggregated and translocated towards the Orai1-containing plasma membrane in association with the microtubule plus-end binding protein EB1. In contrast, STIM2 is constitutively aggregated without significant trafficking or association with microtubules. These results show the distinct role of STIM1 and STIM2 in SOCE and cellular function of cervical cancer cells.

Efficacy of rice bran fermentation in cosmetics and skin care products / Eficácia da fermentação de farelo de arroz em cosméticos e produtos para cuidados com a pele

This study aims to develop rice bran-based skin care products with moisturizing, whitening and anti-wrinkle effects similar to Pitera (a natural by-product of sake lees fermentation) but without alcohol irritation for sensitive skin. To achieve this objective, bran from organic indica rice was fermented by lactic acid bacteria in a safe and pollution-free environment. In terms of anti-oxidation, the DPPH ．free radical scavenging ability of 100.0 mg/mL bran fermentation solution was 71.4% of that of vitamin C of the same concentration; and its Fe2+ chelating ability was 79.0% of that of EDTA of the same concentration. Moreover, the superoxide anion scavenging ability of 10.0 mg/mL bran fermentation solution was equivalent to 42.9% of that of BHT of similar concentration. With respect to inhibition of melanin synthesis, the bran fermentation solution's ability to inhibit the synthesis of dopachrome, the intermediate of melanin, was positively correlated to its concentration, i.e., the higher the concentration of the bran fermentation solution was, the better the inhibition ability was. The IC50 of bran fermentation solution was 9.23 mg/mL while, for comparison, that of arbutin was 0.52 mg/mL. Furthermore, according to the cell survival assay, no obvious cytotoxic effect was found with the increase of the concentration of the bran fermentation solution. As for whitening evaluation, the whitening improvement rate was 9.29% in 20% dilution, 5.36% in 15% dilution, 3.69% in 10% dilution, 2.43% in 5% dilution, 0.35% in 1% dilution in a 30-day test. In the moisturizing evaluation, the moisturizing improvement rate was 44.31% in 20% dilution, 20.48% in 15% dilution, 7.68% in 10% dilution, 6.02% in 5% dilution and 2.02% in 1% dilution. Based on the experimental results, the alcohol-free rice bran fermentation solution not only did not cause irritation but also had antiaging, melanin synthesis inhibition, whitening and moisturizing effects. Therefore, it is advisable to add rice bran fermentation solution to cleaning mousse, shower gel, serum and essence to turn bran from compost of agricultural waste (cradle to grave) into a natural raw material (cradle to cradle) of the cosmetic industry, creating new value of rice bran.

Este estudo tem como objetivo desenvolver produtos de cuidados com a pele baseados em farelo de arroz com hidratação, branqueamento e efeitos antiarrugas semelhantes à Pitera (um subproduto natural da fermentação de sauces), mas sem irritação com álcool para a pele sensível. Para alcançar esse objetivo, o farelo do arroz indica orgânico foi fermentado por bactérias do ácido lático em um ambiente seguro e livre de poluição. Em termos de antioxidação, a capacidade de eliminação radical de DPPH.free de 100,0 mg / mL de solução de fermentação de farelo foi de 71,4% da vitamina C da mesma concentração; E sua capacidade de quelação Fe2 + foi de 79,0% da EDTA da mesma concentração. Além disso, a capacidade de eliminação de aniões superóxido de 10,0 mg / mL de solução de fermentação de farelo era equivalente a 42,9% da BHT de concentração similar. Com relação à inibição da síntese de melanina, a capacidade da solução de fermentação do farelo de inibir a síntese do dopachrome, o intermediário da melanina, correlacionou-se positivamente com sua concentração, ou seja, quanto maior a concentração da solução de fermentação do farelo, melhor a capacidade de inibição estava. A solução de IC50 de fermentação de farelo foi de 9,23 mg / mL enquanto que, para comparação, a arbutina era de 0,52 mg / mL. Além disso, de acordo com o ensaio de sobrevivência celular, nenhum efeito citotóxico óbvio foi encontrado com o aumento da concentração da solução de fermentação de farelo. Quanto à avaliação do branqueamento, a taxa de branqueamento foi de 9,29% na diluição de 20%, 5,36% na diluição de 15%, 3,69% na diluição de 10%, 2,43% na diluição de 5%, 0,35% na diluição de 1% em um teste de 30 dias . Na avaliação hidratante, a taxa de melhora hidratante foi de 44,31% em 20% de diluição, 20,48% em diluição de 15%, 7,68% em diluição de 10%, 6,02% em diluição de 5% e 2,02% em diluição a 1%. Com base nos resultados experimentais, a solução de fermentação de farelo de arroz sem álcool não só não causou irritação, mas também teve anti-envelhecimento, inibição da síntese de melanina, branqueamento e efeitos hidratantes. Portanto, é aconselhável adicionar solução de fermentação de farelo de arroz para mousse de limpeza, gel de banho, soro e essência para transformar o farelo do composto de resíduos agrícolas (berço a túmulo) em uma matéria-prima natural (berço para berço) da indústria de cosméticos, criando Novo valor do farelo de arroz.

Minoxidil is a potential neuroprotective drug for paclitaxel-induced peripheral neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer treatment. No medication has been shown to be effective in the treatment of CIPN. This study aims to integrate the image-based high-content screening, mouse behavior models and mechanistic cell-based assays to discover potential neuroprotective drugs. Among screened compounds, minoxidil showed the most potent neuroprotective effect against paclitaxel, with regard to neurite outgrowth of dorsal root ganglia (DRG). Minoxidil protected mice from thermal insensitivity and alleviated mechanical allodynia in paclitaxel-treated mice. The ultrastructure and quantified G-ratio of myelin integrity of sciatic nerve tissues supported the observations in mouse behavioral tests. The mechanistic study on DRG neurons suggested that minoxidil suppressed neuroinflammation and remodeled the dysregulation of intracellular calcium homeostasis provoked by paclitaxel. Importantly, minoxidil showed a synergistic anti-tumor effect with paclitaxel both in tumor xenograft models of cervical and breast cancer. Interestingly, the quantitative assays on hair length and hair growth both exhibited that minoxidil significantly improved the hair quality after chemotherapy. Since minoxidil is a drug approved by the Food and Drug Administration (FDA), the safety and biocompatibility are well documented. The immediate next step is to launch an early-stage clinical trial intending to prevent CIPN by minoxidil.

Integrating Image-Based High-Content Screening with Mouse Models Identifies 5-Hydroxydecanoate as a Neuroprotective Drug for Paclitaxel-Induced Neuropathy.

Chemotherapy-induced neurotoxicity is a common adverse effect of cancer treatment. No medication has been shown to be effective in the prevention or treatment of chemotherapy-induced neurotoxicity. This study aimed to discover potential neuroprotective drugs for paclitaxel-induced neurotoxicity. An image-based high-content platform was first developed to screen for potential neuroprotective drugs. The screening system comprised of automated image acquisition and multiparameter analysis, including neuronal viability, neurite outgrowth, and synaptogenesis. By this platform, we obtained a candidate list from compound libraries. In the drug screening from compound libraries of ion channel ligands, REDOX and GABAergic ligands, 5-hydroxydecanoate (5-HD) exhibited the most significant neuroprotective effects against paclitaxel-induced neurotoxicity in both cortical and dorsal root ganglion (DRG) neurons. In mouse behavioral tests, 5-HD restored the thermal sensitivity and alleviated mechanical allodynia induced by paclitaxel. Electron micrographs of sciatic nerve revealed that 5-HD reduced the damages caused by paclitaxel in the nonmyelinated and smaller myelinated fibers. The mechanistic study on DRG neurons suggested that 5-HD rescued the dysregulation of intracellular calcium homeostasis provoked by paclitaxel. Importantly, 5-HD did not jeopardize the antitumor effect of paclitaxel in tumor xenograft models. In conclusion, we established an imaged-based high-content screening platform and a protocol for verifying the neuroprotective effect in vivo, by which 5-HD was identified and validated as a potential neuroprotective drug for paclitaxel-induced neuropathy.

Sex differences and the modulating effects of gonadal hormones on basal and the stressor-decreased newly proliferative cells and neuroblasts in dentate gyrus.

This study was undertaken to assess sex differences and the modulating effects of gonad intactness and the estrous phase on basal and the stressor-decreased cell proliferation and early differentiation in Balb/C mouse dentate gyrus (DG). Besides, we compared the stress-reversing effects exerted by the presence of male and female Balb/C mouse odors in stressed male and female mouse DG in this regard. Female mice had lower baselines in the number of newly proliferated cells and neuroblasts than male mice. Although the stressor induced decreases in the number of newly proliferative cells and neuroblasts in both male and female DG, an obvious decrease in neuronal lineage commitment was observed in female DG. Moreover, ovariectomy induced decreases in baselines in the number of proliferative cells and neuroblasts but did not affect the stressor-induced decrease in neuronal lineage commitment in female DG. Interestingly, pro-estrous mice exhibited the stressor-decreased neuronal lineage commitment, while estrous and diestrous mice did not display such a decrease. Furthermore, orchidectomy did not affect basal or the stressor-decreased newly proliferative cells or neuroblasts in male DG. Finally, male odors were less effective than female odors in abolishing the stressor-decreased neuronal lineage commitment in female mice, while male and female odors were comparable in reversing the stressor-decreased newly proliferated cells and neuroblasts in male mice. The protective effects of mouse odors' company in the stressed male mouse DG were associated with local BDNF and NGF replenishment. Taken together, sexual differences in baselines in the number of newly proliferative cells, neuroblasts, and the sensitivity to stress-altered neuronal lineage commitment in the DG could be, in part, due to gonadal hormone differences between the two sexes. Mouse odors may reverse stressor-decreased newly proliferative cells and neuroblasts in male, but not in female, mouse DG by restoring BDNF and NGF levels.

Companions reverse stressor-induced decreases in neurogenesis and cocaine conditioning possibly by restoring BDNF and NGF levels in dentate gyrus.

The presence of companions can reverse the stressor-induced decrease in neurogenesis in mouse dentate gyrus (DG). In this study, we decided to study the underlying mechanisms of the companions' protective effect and to assess whether two DG neurogenesis-related memories, cocaine-induced conditioned place preference (CPP) and spatial memory, can be affected by our stressor and companions. Neurotrophin levels in DG were measured, in this regard, to reveal their roles in mediating the stressors' and companions' effect. We found that the stressor did not affect NT-3 but acutely decreased NGF and BDNF levels in DG. The presence of companions abolished these stressor-decreased NGF and BDNF levels. Neither the stressor nor the presence of companions affected TrkA, TrkB or TrkC expression in DG. Pre-exposure to the stressor rendered deficits in cocaine-induced CPP and spatial memory, while companions reversed the stressor-decreased cocaine-induced CPP. Intra-ventricular infusion with K252a, a mixed TrkA and TrkB antagonist, did not affect the protective effects of companions on local NGF, BDNF levels in DG, but abolished the companions' protective effects against the stressor-decreased DG neurogenesis and cocaine-induced CPP. Systemic pretreatment with 7,8-dihydroxyflavone (DHF), a selective TrkB agonist, did not affect baseline, the stressor-stimulated corticosterone (CORT) secretion or local NGF, BDNF levels in DG, but in part mimicked companions' protective effects. These results, taken together, indicate that stressor-decreased NGF and BDNF levels in DG could be involved in the stressor-decreased DG neurogenesis and cocaine conditioning. The presence of companions reverses the stressor-decreased DG neurogenesis and cocaine conditioning possibly by restoring BDNF and NGF levels in DG.