CD70-Targeted Allogeneic CAR T-Cell Therapy for Advanced Clear Cell Renal Cell Carcinoma.

Therapeutic approaches for clear cell renal cell carcinoma (ccRCC) remain limited; however, chimeric antigen receptor (CAR) T-cell therapies may offer novel treatment options. CTX130, an allogeneic CD70-targeting CAR T-cell product, was developed for the treatment of advanced or refractory ccRCC. We report that CTX130 showed favorable preclinical proliferation and cytotoxicity profiles and completely regressed RCC xenograft tumors. We also report results from 16 patients with relapsed/refractory ccRCC who received CTX130 in a phase I, multicenter, first-in-human clinical trial. No patients encountered dose-limiting toxicity, and disease control was achieved in 81.3% of patients. One patient remains in a durable complete response at 3 years. Finally, we report on a next-generation CAR T construct, CTX131, in which synergistic potency edits to CTX130 confer improved expansion and efficacy in preclinical studies. These data represent a proof of concept for the treatment of ccRCC and other CD70+ malignancies with CD70-targeted allogeneic CAR T cells. SIGNIFICANCE: Although the role of CAR T cells is well established in hematologic malignancies, the clinical experience in solid tumors has been disappointing. This clinical trial demonstrates the first complete response in a patient with RCC, reinforcing the potential benefit of CAR T cells in the treatment of solid tumors.

Ethnobotanical study on medicinal plants used by the Yi people in Xiaoliangshan, Yunnan Province, SW China.

ETHNOPHARMACOLOGICAL RELEVANCE: The Yi people in the Xiaoliangshan region in southwest China have a unique practice of combining ritual treatment and traditional medicine to care for patients. Despite increasing urbanization in the area, they have managed to preserve their distinctive lifestyle and extensive knowledge of traditional medicinal plants, setting them apart from other regions. However, there is a lack of systematic documentation on the knowledge of traditional medicinal plants used by the Yi people in Xiaoliangshan. AIM OF THE STUDY: This research aims to achieve the following objectives: 1. Document the diversity of medicinal plants used by the Yi people and explore their therapeutic usages. 2. Evaluate and analyze the main types of diseases with a high incidence in the local area and identify the types of medicinal plants used to treat these diseases. 3. Explore the underlying geographical and human factors influencing both disease prevalence and medicinal plant usage. METHODS: Ethnobotanical research methods were used to record and analyze the medicinal plants used by the Yi in Xiaoliangshan. Experts identified all plant specimens collected during ethnobotanical field surveys. The types of diseases treated by medicinal plants were classified according to the International Classification of Primary Care -2nd. RESULTS: A total of 125 medicinal plants were recorded after interviewing 193 participants. Of the medicinal plants identified, those with over 100 use reports were Paris polyphylla (202 use reports), Taxillus sutchuenensis (183), Artemisia indica (149), and Papaver somniferum (113). A total of 14 disease categories were recorded, with those related to the following categories having higher Informant Consensus factor values (ICF ≥0.85): Pregnancy, Childbearing, Family Planning, General and Unspecified, Urological, Respiratory, Musculoskeletal, and Skin. The highest quantity of medicinal plants is utilized to improve specific diseases and health problems, namely those related to Digestion, Skin, and Musculoskeletal. Fewer plant species were utilized for diseases or health issues associated with Eyes, Psychological, or Pregnancy, Childbearing, and Family Planning. The use reports from the informants also revealed how some medicinal plants are used to treat a variety of diseases or health issues. For instance, Malva pusilla is used for inducing abortion, treating postpartum hemorrhage, and joint sprains; Artemisia indica is used for treating malaria; Argentina lineata is used to remedy tuberculosis and malaria. Taxillus sutchuenensis is used for dealing with cold, pneumonia, and other ailments. CONCLUSIONS: The Yi people in Xiaoliangshan have a rich knowledge of traditional medicinal plants. Decoction and wine brewing are the most common processing methods used for these plants, which are utilized to treat a wide range of diseases. The characteristics of the medicinal use of the Yi people reflects the alpine mountainous environment in which they live, and their medical practices are closely related to traditional healing culture. This study enhances our understanding of the Yi traditional medicine via documentation and offers a valuable reference for future research and the development of new drugs.

An ethnobotanical study of wild edible plants used by the Tibetan in the Rongjia River Valley, Tibet, China.

BACKGROUND: Wild edible plants (WEPs) play a crucial role in communities with limited communication with the outside world, where unstable factors, such as poor food supply and insufficient access to timely nutritional supplementation, are common, as in the Himalayan region. To document the traditional knowledge of WEPs and explore their significance for communities with minimal global economic exchange, an ethnobotanical study was conducted in the town of Rongjia, which lies in a narrow valley near Mount Everest, Tibet, China. METHODS: This ethnobotanical study was conducted in three villages in the Rongjia River Valley between August 2021 and June 2023. Semi-structured interviews and participatory observations were used to collect information on WEPs. The fieldwork was performed with the assistance of local guides. Voucher specimens were collected from each documented plant species for taxonomic identification. We used the use report (UR) and relative frequency of citations (RFC) to evaluate the comprehensive utilization value of WEPs. RESULTS: We interviewed 161 informants who provided us with 2499 use reports. We collected 50 WEPs belonging to 28 families and 42 genera used by the Tibetan people in the Rongjia River Valley. WEPs are used in vegetables, fruits, seasonings, healthcare foods, substitute grains, and beverages. Wild vegetables were the most commonly used, followed by wild fruits. Leaves were the most commonly consumed part of the plant. The three most important WEPs ordered by RFC values were Rosa sericea var. glandulosa Osmaston (RFC = 0.76), Zanthoxylum bungeanum Maxim. (RFC = 0.75), and Urtica hyperborea Jacquem. ex Wedd. (RFC = 0.71). Other than that, we also document some of WEPs used in the past. Arisaema erubescens Schott, Pinellia ternata (Thunb.) Makino, and Satyrium nepalense var. ciliatum (Lindl.) Hook. f. used to serve as important substitute grains, are no longer in use, however, they remain vivid in the memories of older people. CONCLUSIONS: WEPs included wild vegetables, fruits, seasonings, healthcare food, and substitute grains for Tibetan people in the Rongjia River Valley. Some WEPs have become important cultural symbols for older people, which can help in understanding the relationship between plants and local people in the past. In addition, WEPs can increase the resilience of local people living in remote areas when facing sudden destabilizing events in future. This is the significance of WEPs for communities with minimal global economic exchange. Therefore, we suggest that future studies focus more on WEPs in communities with limited communication with the world to improve their resilience.

High expression of the circadian clock gene NPAS2 is associated with progression and poor prognosis of gastric cancer: A single-center study.

BACKGROUND: The prognostic assessment of patients after surgical resection of gastric cancer (GC) patients is critical. However, the role of the circadian clock gene NPAS2 expression in GC remains unknown. AIM: To explore the relationship between NPAS2 and the survival prognosis of GC patients and clarify its role in evaluating GC prognosis. METHODS: The tumor tissues and clinical data of 101 patients with GC were collected retrospectively. Immunohistochemical staining (IHC) was used to detect the expression of NPAS2 protein in GC and adjacent tissues. Univariate and multivariate Cox regression analysis was used to determine the independent prognostic factors of GC, and a nomogram prediction model was established. The receiver operating characteristic (ROC) curve, the ROC area under the curve, the calibration curve, and C-index were used to evaluate the predictive effectiveness of the model. Kaplan Meier analysis was used to compare the risk stratification of subgroups according to the median score in the nomogram model of each patient. RESULTS: Microarray IHC analysis showed that the positive rate of NPAS2 protein expression in GC tissues was 65.35%, which was significantly higher than 30.69% in adjacent tissues. The high expression of NPAS2 was correlated with tumor-node-metastasis (TNM) stage (P < 0.05), pN stage (P < 0.05), metastasis (P < 0.05), venous invasion (P < 0.05), lymphatic invasion (P < 0.05), and lymph node positive (P < 0.05) of GC. Kaplan Meier survival analysis showed that the 3-year overall survival (OS) of patients with high NPAS2 expression was significantly shortened (P < 0.0001). Univariate and multivariate COX regression analysis showed that TNM stage (P = 0.009), metastasis (P = 0.009), and NPAS2 expression (P = 0.020) were independent prognostic factors of OS in GC patients for 3 years. The nomogram prediction model based on independent prognostic factors has a C-Index of 0.740 (95%CI: 0.713-0.767). Furthermore, subgroup analysis showed that the 3-year OS time of the high-risk group was significantly lower than that of the low-risk group (P < 0.0001). CONCLUSION: NPAS2 is highly expressed in GC tissues and is closely related to worse OS in patients. Therefore, the evaluation of NPAS2 expression may be a potential marker for GC prognosis evaluation. Notably, the nomogram model based on NPAS2 can improve the accuracy of GC prognosis prediction and assist clinicians in postoperative patient management and decision-making.

A comparison of traditional plant knowledge between Daman people and Tibetans in Gyirong River Valley, Tibet, China.

BACKGROUND: By comparing the differences in plant use between various cultures or regions, we can gain a better understanding of traditional knowledge of plant use among different groups, which may lead to a more objective understanding. Even though the Tibetan and Daman people live in the same ecosystem in Gyirong town, China, their cultural backgrounds and livelihoods differ. Therefore, the objective of this study is to document the traditional knowledge of plant use among the Daman people and compare it with the local Tibetan knowledge of plant use. By doing so, we aim to explore the relationship between plant selection and use and the cultural backgrounds of different groups. METHODS: During fieldwork, ethnobotanical data were collected using various methods including free listings, key informant interviews, and semi-structured interviews. To quantify the importance of plant species in the Daman people's culture, the culture importance index, informant consensus factor index, and The Index of Agreement on Species consensus (IASc) were used. In addition, we cited previous ethnobotanical survey data from the Tibetan in Gyirong. To more comprehensively compare the differences in plant use between the Daman and Tibetan, this study constructed a knowledge network to compare the knowledge differences between the two groups. RESULTS: In this study, traditional knowledge was collected from 32 Daman informants, resulting in a total of 68 species belonging to 39 families mentioned by Daman people and 111 species mentioned by Tibetans. Of these, 58 plants were used by both populations. The plants were classified into 3 categories and 28 subcategories, with 22 identical classes in both groups. The majority of use categories showed a high degree of sharing in both groups, and the Tibetan people had more plant use categories than the Daman people. Five plants with IASc value > 0.5 were identified in both groups: Rhododendron anthopogon D. Don, Artemisia japonica Thunb., Juniperus indica Bertol., Gastrodia elata Blume, and Rheum australe D. Don. The analysis of the knowledge network revealed a 66% overlap between the knowledge of the Daman and the knowledge of the Tibetans. Additionally, the plant knowledge of Tibetan people was found to be richer and more complex than that of the Daman people. However, the Daman people possess 30 unique knowledge items. CONCLUSIONS: From the perspective of plant use, the history of the Daman people's discrete migration on the border between China and Nepal allows them to retain their own knowledge of plant use. The status quo of joining Chinese nationality and settling in Gyirong town allows them to gradually integrate into the local Tibetan society. In summary, despite living in the same ecosystem and biodiversity background, the plant utilization of the Daman people and Tibetans still shows significant differences, which are due to their different cultural backgrounds and social status.

An ethnobotanical study on wild plants used by Tibetan people in Gyirong Valley, Tibet, China.

BACKGROUND: Gyirong Valley known as the "Back Garden of the Himalayas" is located in the core area of the Everest National Nature Reserve. It is also one of the important ports from ancient Tibet to Kathmandu, Nepal, since ancient times. Over the years, the Tibetans of Gyirong had accumulated sufficient traditional knowledge about local plant resources. However, there is almost no comprehensive report available on ethnobotanical knowledge about the local people. The purposes of this study were to (1) conduct a comprehensive study of wild plants used by Tibetan people in Gyirong Valley and record the traditional knowledge associated with wild useful plants, (2) explore the influence of Tibetan traditional culture and economic development on the use of wild plants by local people, and (3) explore the characteristics of traditional knowledge about wild plants of Tibetans in Gyirong. METHODS: Ethnobotanical data were documented through free listings, key informant interviews and semi-structured interviews during fieldwork. The culture importance index and the informant consensus factor index were used as quantitative indices. RESULTS: In total, 120 informants (61 women and 59 men) and 3333 use reports and 111 wild plant species belonging to 39 families and 81 genera were included. These use reports were then classified into 27 categories belonging to three major categories. The use category that contained the most plant species was edible plants (62), followed by medicinal plants (32) and economic plants (22), and other uses (71). Plants with high CI included Allium prattii, Neopicrorhiza scrophulariiflora, Gymnadenia orchidis, Rhododendron anthopogon and Fritillaria cirrhosa. Thirty-six species of plants in the catalog of Gyirong and Yadong were the same, but only 17 species were the same in Gyirong and Burang. There were only 11 overlapping species between all the three regions. CONCLUSION: Tibetans of Gyirong have rich and unique knowledge about plant use, and wild edible and medicinal plants play an important role in the nutrition and health protection of local people. However, traditional knowledge is slowly being lost and is being hit by modern tourism. In the future, more attention needs to be paid to the important role of traditional knowledge in biodiversity conservation.

miR-210-3p protects against osteoarthritis through inhibiting subchondral angiogenesis by targeting the expression of TGFBR1 and ID4.

Excessive subchondral angiogenesis is a key pathological feature of osteoarthritis (OA), as it alters the balance of subchondral bone remodeling and causes progressive cartilage degradation. We previously found that miR-210-3p correlates negatively with angiogenesis, though the specific mechanism of miR-210-3p-related angiogenesis in subchondral bone during OA progression remains unclear. This study was conducted to identify the miR-210-3p-modulating subchondral angiogenesis mechanism in OA and investigate its therapeutic effect. We found that miR-210-3p expression correlated negatively with subchondral endomucin positive (Emcn+) vasculature in the knee joints of OA mice. miR-210-3p overexpression regulated the angiogenic ability of endothelial cells (ECs) under hypoxic conditions in vitro. Mechanistically, miR-210-3p inhibited ECs angiogenesis by suppressing transforming growth factor beta receptor 1 (TGFBR1) mRNA translation and degrading DNA-binding inhibitor 4 (ID4) mRNA. In addition, TGFBR1 downregulated the expression of ID4. Reduced ID4 levels led to a negative feedback regulation of TGFBR1, enhancing the inhibitory effect of miR-210-3p on angiogenesis. In OA mice, miR-210-3p overexpression in ECs via adeno-associated virus (AAV) alleviated cartilage degradation, suppressed the type 17 immune response and relieved symptoms by attenuating subchondral Emcn+ vasculature and subchondral bone remodeling. In conclusion, we identified a miR-210-3p/TGFBR1/ID4 axis in subchondral ECs that modulates OA progression via subchondral angiogenesis, representing a potential OA therapy target.

NPM1 is a diagnostic and prognostic biomarker associated with the clinicopathological characteristics of gastric cancer.

NPM1 plays an important role in the occurrence and development of leukemia and various solid tumors. This study aimed to investigate the expression of NPM1 in gastric cancer (GC) and adjacent normal tissues, study the relationship between NPM1 expression and clinicopathological characteristics in GC patients, and explore the impact of NPM1 expression on the diagnosis and prognosis of GC. We used tissue microarray immunohistochemical analysis to examine the expression level of NPM1 in GC and adjacent tissues and analyzed the relationship between NPM1 expression, clinicopathological factors, and GC prognosis. Prognostic values of NPM1 mRNA were also investigated using an online database. qRT-PCR was used to detect the expression of NPM1 mRNA in cancer and adjacent tissues. According to microarray immunohistochemical analysis and qRT-PCR results, NPM1 had a high expression in all adjacent normal tissues. Microarray immunohistochemical analyses demonstrated that the NPM1 was lowly expressed in 75.5% of GC tissues but highly expressed in 24.5% of GC tissues. qRT-PCR results showed NPM1 mRNA low expression in most GC tissues. NPM1 high expression group was associated with a better overall survival rate and disease-free survival rate than the NPM1 low expression group (p<0.01). This result is consistent with that of the online database. The receiver operating characteristics curve showed that NPM1 was valuable in the diagnosis of GC. The assessment of NPM1 expression in GC samples may represent a useful tool for GC diagnosis and prognosis assessment.

An ethnobotany survey of wild plants used by the Tibetan people of the Yadong River Valley, Tibet, China.

INTRODUCTION: Plant resources gathered from the wild are important sources of livelihood needs, especially for low-income populations living in remote areas, who rely on these plants for food, fuelwood, medicine and building materials. Yadong County is a valley at the border between the China, India and Bhutan in southern Tibet. Yadong is rich in biodiversity and culture, but ethnobotanical knowledge has not been systematically studied. This study aimed to document the ethnobotanical knowledge of Tibetans in Yadong County. METHODS: Ethnobotanical data were documented through free listings, key informant interviews, and semi-structured interviews during fieldwork. The culture importance index (CI) and informant consensus factor index (FIC) were used as the quantitative indices. RESULTS: In total, 163 informants (46 women and 117 men). A total of 3,031 use reports and 121 plant species belonging to 52 families and 91 genera were included. These use reports were then classified into 20 categories belonging to 9 major categories. The utilisation category that containing the most plant species was food, followed by economic, medicine, animal feed, social uses, other uses, environmental uses, materials and fuels. Among the economic plants, 32 medicinal plants are traditionally used in the local region. Plants with high CI included Fritillaria cirrhosa, Neopicrorhiza scrophulariiflora, Betula utilis, Rheum nobile, and Urtica hyperborean. CONCLUSION: This research demonstrates the diversity of the types and functions of Yadong Tibetan traditional plant knowledge. Knowledge of edible and medicinal plants in this area is prominent, reflecting the ability to cope with the lack of fruits and vegetables and basic family medical care. There were exchanges between the traditional plant culture in the study area and its surroundings. With socioeconomic development, the commercial value of medicinal plants has increased, and locals are also seeking ways to adoptsustainable development to cope with the excessive consumption of plant resources.

Epigallocatechin-3-O-gallate ameliorates oxidative stress-induced chondrocyte dysfunction and exerts chondroprotective effects via the Keap1/Nrf2/ARE signaling pathway.

Oxidative stress-induced degeneration and dysfunction of chondrocytes play a key role in the pathological progression of osteoarthritis (OA), a common degenerative joint disease in the elderly. Epigallocatechin-3-O-gallate (EGCG) increases Nrf2-mediated antioxidase expression levels. We aimed to determine the effects of EGCG on C28/I2 human chondrocytes subjected to interleukin-1ß (IL-1ß)-induced oxidative stress. EGCG suppressed IL-1ß-induced oxidative stress, as indicated by decreased malondialdehyde (MDA) and reactive oxygen species (ROS) generation. Additionally, EGCG attenuated the IL-1ß-induced reduction in cartilage matrix generated by chondrocytes by upregulating collagen II, aggrecan, sulfated proteoglycans, and SRY-box transcription factor 9 (SOX9). EGCG reversed the IL-1ß-induced increased cyclooxygenase 2 (COX2), inducible nitric oxide synthase (iNOS), collagen X, and matrix metalloproteinases (MMPs). Furthermore, EGCG inhibited apoptosis and senescence of IL-1ß-treated chondrocytes, as indicated by the decrease in mitochondrial membrane potential and senescence-associated ß-galactosidase-positive cells, respectively. Mechanically, EGCG upregulated nuclear factor erythroid 2-related factor 2 (Nrf2), oxygenase-1 (HO-1), and NADPH quinone oxidoreductase1 (NQO1). The antioxidant and chondroprotective effects of EGCG were blocked by ML385, a Keap1/Nrf2/ARE signaling pathway inhibitor. Thus, EGCG ameliorated oxidative stress-induced chondrocyte dysfunction and exerted chondroprotective effects via Keap1/Nrf2/ARE signaling. This provides a novel perspective on the molecular mechanisms underlying the therapeutic effects of EGCG on OA.

Ellagic acid attenuates interleukin-1ß-induced oxidative stress and exerts protective effects on chondrocytes through the Kelch-like ECH-associated protein 1 (Keap1)/ Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway.

Osteoarthritis (OA) is the most prevalent type of degenerative joint disease, and its pathological progression is highly associated with oxidative stress. Natural antioxidants can attenuate oxidative stress and chondrocyte injury, suggesting that antioxidants have potential applications in the management of OA. Ellagic acid (EA), a natural polyphenol derived from fruits or nuts, exerts antioxidant and anti-inflammatory effects in diseases related to oxidative stress. Herein, we investigated the effects of EA on interleukin-1ß (IL-1ß)-induced oxidative stress and degeneration in C28/I2 human chondrocytes. EA efficiently suppressed IL-1ß-induced oxidative stress and ameliorated oxidative stress-induced dysfunction of chondrocytes, as indicated by the promotion of cartilage matrix secretion. Moreover, EA remarkably suppressed cell apoptosis and senescence, and reduced the expression of proinflammatory factors and metalloproteinases, suggesting that EA could alleviate chondrocyte injury under oxidative stress. Mechanistically, EA upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) as well as its downstream targets NADPH quinone oxidoreductase 1 and heme oxygenase-1. ML385, a specific Keap1/Nrf2 pathway inhibitor, blocked the antioxidant and chondroprotective effects of EA. Our findings demonstrated that EA could attenuate oxidative stress and exert protective effects on chondrocytes by upregulating the Keap1/Nrf2 signaling pathway.

Plants for making wooden bowls and related traditional knowledge in the Gyirong Valley, Tibet, China.

BACKGROUND: The wooden bowl is an important symbol of the Tibetan cultures, yet, in China, little has been documented regarding the raw materials used to make these items as well as their cultural significance in Tibet. This study explores the ethnobotanical uses of plants used to make wooden bowls to understand their sustainability, cultural significance, and current status of related traditional knowledge in Gyirong Town, which is one of the most famous places for wooden bowl making. MATERIALS AND METHODS: Between 2019 and 2021, key informant interviews, semi-structured interviews, and participatory observations were used to conduct ethnobotanical field surveys in Gyirong Valley. The field work was performed with the assistance of local guides. In this study, we utilized a use-report (UR) to reflect the number of mentions of a species by locals. RESULTS: Our results show that 16 different plants are used during the wooden bowl making process, of which nine are used as raw materials, three for dyeing, and four for varnishing. Although communities rely heavily on these plants, good management and collection methods were observed. We also documented the use of Fallopia denticulata as a red dye and four species of Impatiens as wood varnishes for the first time. CONCLUSION: The wooden bowl craftsmen and their housewives have a wealth of traditional knowledge of using plants to make wooden bowls in Gyirong Town. And the wooden bowls are now also offering benefits to the locals as well. The government and local people are committed to the protection and development of traditional knowledge related to wooden bowls, and this knowledge maintains a healthy degree of vitality. This research can provide insights into the vitality of traditional handicrafts that are facing challenges and promote their protection.

A study of the plant folk nomenclature of the Yi people in Xiaoliangshan, Yunnan Province, China, and the implications for protecting biodiversity.

BACKGROUND: Folk plant nomenclature is a part of knowledge of indigenous people often used to distinguish plant species. This study aimed to document the folk botanical nomenclature of the Yi people in Xiaoliangshan, Yunnan Province, which has not been systematically investigated to date. The results of this study will assist in conserving biodiversity and the language of the Yi people and will promote the transmission of ethnobotanical knowledge. METHODS: An ethnobotanical survey of plants used by the Yi people in Xiaoliangshan, Yunnan Province, was conducted from September 2019 to August 2021. Semi-structured interviews and key informant interviews were conducted to collect and document ethnobotanical information, which was then used to analyse the folk botanical nomenclature of the Yi people. In addition, the folk names of plants used by the Xiaoliangshan Yi community were compared with those of the Yi people living in the Daliangshan, where the environment is considerably different. RESULTS: In this study, 266 informants were interviewed, and the names of 228 indigenous plants were extracted from 3088 use reports. The nomenclature used by the local Yi people is based on plant characteristics, plant habitat, plant use, and the local culture. By comparing the folk plant names of the Yi people in Xiaoliangshan with those of the Yi people in Daliangshan, we found that the plant names of the two places have some similarities and also with their own unique characters. The important folk plant names of the Yi people in Xiaoliangshan usually have a monosyllable non-binomial structure or have and "divine attributes" in their names. CONCLUSIONS: The Yi people in Xiaoliangshan have a rich and diverse knowledge of plant naming determined by cultural, and environmental factors. The botanical nomenclature of the Yi people has distinct rules and characteristics, and the plant naming directly includes important plants that they believe to be used and protected, which is of great significance to the protection of biodiversity.

Applying rail transit construction waste to make building materials: using the theory of sustainable development.

With the rapid development of the rail industry, a large amount of construction waste will be generated during the construction phase, posing a significant risk of environmental pollution and exacerbating the plight of global resource shortages. This study establishes a green disposal system for rail transportation based on the theory of sustainable development. Shield slag, shield weathered sand, shale, and engineering slag are used as raw materials, and sintered bricks are adopted as their innovative disposal method. The heavy metals in the four types of construction waste and recycled products were tested by X-ray fluorescence analysis technique to analyze the actual environmental pollution risk and explore the influence of the firing stage on the performance of the recycled products through the enrichment factor evaluation method. The results of the physical and chemical property tests of the fired samples showed that the environmental pollution risk of the four recycled products after firing was at a low-risk level (EF < 2), the strength test results showed that the best specimens had a strength rating of 20 MPa and the other performance indicators (frosting degree, lime bursting test) measured also met the requirements of the recycled bricks. This study achieves the harmless treatment of construction waste, provides a disposal system for the green recycling of construction waste from rail transport, and provides a theoretical basis for subsequent studies on the effects of different external conditions on such recycled products.

Oxcarbazepine versus Carbamazepine for the Treatment of Post-Stroke Epilepsy: A Systematic Review and Meta-Analysis.

AIM: To systematically evaluate the medication safety and effectiveness of Oxcarbazepine (OXC) and carbamazepine (CBZ) for the treatment of post-stroke epilepsy (PSE). MATERIAL AND METHODS: We searched Medline and other databases to identify the randomized controlled trials (RCTs) that compare the efficacies of OXC and CBZ in treating PSE. Two authors extracted and analyzed the data independently with Revman 5.3 software. The Q-test and I2 were used to test the statistical heterogeneity. The fixed or random effect models were selected according to heterogeneity. RESULTS: Eight RCTs that include 671 patients were involved in this study. The meta-analyses result showed that the overall efficiency of OXC was significantly better than that of CBZ (OR=4.55, 95% confidence interval (CI) (3.04?6.81)), the overall adverse events (OR=0.27, 95% CI (0.18?0.42), and the incidence of vomiting (OR=0.28, 95% CI (0.09?0.85)) of OXC was significantly less than that of CBZ. No significant differences in the incidence of rash (OR=0.45, 95% CI (0.19?1.07)), lethargy (OR=0.49, 95% CI (0.16?1.45)), and dizziness (OR=0.51, 95% CI (0.20?1.35)) were detected between OXC and CBZ. CONCLUSION: OXC seems to be superior to CBZ in the treatment of PSE, with higher efficacy, and safety than the latter. However, more research on OXC and CBZ in the treatment of PSE is required in the later stage due to the sample size limitation of our study.

Bardoxolone-Methyl Prevents Oxidative Stress-Mediated Apoptosis and Extracellular Matrix Degradation in vitro and Alleviates Osteoarthritis in vivo.

PURPOSE: Oxidative stress-induced chondrocyte apoptosis and extracellular matrix (ECM) degradation plays an important role in the progression of osteoarthritis (OA). Bardoxolone methyl (BM), a semisynthetic triterpenoid, exerts strong effect against oxidative stress. The purpose of the present study was to determine the effectiveness of bardoxolone-methyl (BM) in preventing oxidative stress-induced chondrocyte apoptosis and extracellular ECM degradation in vitro and the role of alleviating OA progression in vivo. METHODS: Oxidative damage was induced by 25 mM tert-butyl hydroperoxide (TBHP) for 24 h in rat chondrocytes. 0.025 and 0.05 µM bardoxolone-methyl (BM) were used in vitro treatment. Ex-vivo cartilage explant model was established to evaluate the effect of BM on oxidative stress-induced ECM degradation. The mouse OA model was induced by surgical destabilization of the medial meniscus. RESULTS: In vitro, 0.025 and 0.05 µM BM reduced TBHP-induced excessive ROS generation, improved cell viability, increased malondialdehyde level and decreased superoxide dismutase level. 0.025 and 0.05 µM BM prevented TBHP-induced mitochondrial damage and apoptosis in chondrocytes BM activated heme oxygenase-1 (HO-1)/NADPH quinone oxidoreductase 1 (NOQ1) signaling pathway through targeting nuclear factor erythroid derived-2-related factor 2 (Nrf2). Additionally, BM treatment enhanced the expression levels of aggrecan and collagen II and inhibited the expression levels of matrix metalloproteinase 9 (MMP 9), MMP 13, Bax and cleaved-caspase-3. BM increased proteoglycan staining area and IOD value in ex vivo cultured experiment cartilage explants and improved the OARSI score, stands, max contact mean intensity, print area and duty cycle in mouse OA model. CONCLUSION: BM prevented oxidative stress-induced chondrocyte apoptosis and ECM degradation in vitro and alleviated OA in vivo, suggesting that BM serves as an effective drug for treatment with OA.

Zizyphus jujuba cv. Muzao polysaccharides enhance intestinal barrier function and improve the survival of septic mice.

This study aimed to examine the role of Zizyphus jujuba cv. Muzao polysaccharides (ZJPs) in protecting intestinal barrier function and the survival of septic mice. The sepsis mouse model was generated through cecal ligation and puncture (CLP) to observe the effect of ZJPs on the function of the intestinal barrier in the context of sepsis. We observed the clinical symptoms and survival time of the mice and evaluated serum inflammatory cytokines, intestinal pathological changes and intestinal permeability. Moreover, tight junction (TJ) proteins and apoptosis-associated proteins in intestinal tissue were examined. Finally, TLR4/NF-κB pathway-related proteins were measured in all groups. The results showed that pretreatment with ZJPs improved clinical and histological scores and reduced intestinal barrier permeability, and the levels of proinflammatory factors were decreased. Pretreatment with ZJPs also upregulated the levels of TJ proteins and downregulated the expression of proapoptotic proteins. Moreover, the activation of TLR4/NF-κB signaling was partly inhibited in septic mice by ZJPs pretreatment. The current study provides evidence that ZJPs have the potential to protect intestinal barrier function and improve the survival of septic mice via the attenuation of TLR4/NF-κB inflammatory signaling. PRACTICAL APPLICATIONS: This study reports the potential protective effect of ZJPs against cecal ligation and puncture (CLP)-induced sepsis. Our data reveal that CLP induced damage to the gut mucosal barrier, inflammation, and apoptosis in intestinal tissues. However, pretreatment with ZJPs improved clinical and histological scores, reduced intestinal barrier permeability, and decreased the levels of proinflammatory factors in mice. Pretreatment with ZJPs also upregulated the levels of TJ proteins and downregulated the expression of proapoptotic proteins. Moreover, the activation of TLR4/NF-κB signaling was partly inhibited in septic mice after ZJPs pretreatment. These findings provide evidence that pretreatment with ZJPs has the potential to attenuate CLP-induced gut damage in mice by restraining inflammation and apoptosis via the attenuation of NF-κB signaling. It provides a basis for further study of ZJPs in sepsis.

Cell-derived decellularized extracellular matrix scaffolds for articular cartilage repair.

Articular cartilage repair remains a great clinical challenge. Tissue engineering approaches based on decellularized extracellular matrix (dECM) scaffolds show promise for facilitating articular cartilage repair. Traditional regenerative approaches currently used in clinical practice, such as microfracture, mosaicplasty, and autologous chondrocyte implantation, can improve cartilage repair and show therapeutic effect to some degree; however, the long-term curative effect is suboptimal. As dECM prepared by proper decellularization procedures is a biodegradable material, which provides space for regeneration tissue growth, possesses low immunogenicity, and retains most of its bioactive molecules that maintain tissue homeostasis and facilitate tissue repair, dECM scaffolds may provide a biomimetic microenvironment promoting cell attachment, proliferation, and chondrogenic differentiation. Currently, cell-derived dECM scaffolds have become a research hotspot in the field of cartilage tissue engineering, as ECM derived from cells cultured in vitro has many advantages compared with native cartilage ECM. This review describes cell types used to secrete ECM, methods of inducing cells to secrete cartilage-like ECM and decellularization methods to prepare cell-derived dECM. The potential mechanism of dECM scaffolds on cartilage repair, methods for improving the mechanical strength of cell-derived dECM scaffolds, and future perspectives on cell-derived dECM scaffolds are also discussed in this review.

Stearoyl-CoA Desaturase-2 in Murine Development, Metabolism, and Disease.

Stearoyl-CoA Desaturase-2 (SCD2) is a member of the Stearoyl-CoA Desaturase (SCD) family of enzymes that catalyze the rate-limiting step in monounsaturated fatty acid (MUFA) synthesis. The MUFAs palmitoleoyl-CoA (16:1n7) and oleoyl-CoA (18:1n9) are the major products of SCD2. Palmitoleoyl-CoA and oleoyl-CoA have various roles, from being a source of energy to signaling molecules. Under normal feeding conditions, SCD2 is ubiquitously expressed and is the predominant SCD isoform in the brain. However, obesogenic diets highly induce SCD2 in adipose tissue, lung, and kidney. Here we provide a comprehensive review of SCD2 in mouse development, metabolism, and various diseases, such as obesity, chronic kidney disease, Alzheimer's disease, multiple sclerosis, and Parkinson's disease. In addition, we show that bone mineral density is decreased in SCD2KO mice under high-fat feeding conditions and that SCD2 is not required for preadipocyte differentiation or the expression of PPARγ in vivo despite being required in vitro.

Ethnobotanical survey and evaluation of traditional mosquito repellent plants of Dai people in Xishuangbanna, Yunnan Province, China.

ETHNOPHARMACOLOGICAL RELEVANCE: Dengue is one of the most important pervasive diseases in many regions of the world, including China. There is an urgent need for new repellents, including plant derivatives, due to the resistance, toxicity, and non-degradability of synthetic insecticides. Traditional plant-based remedies may provide potential avenues for developing new strategies. AIMS OF THE STUDY: The aims of this study were to 1) document the traditional mosquitoes repellent plants used by the Dai people of Xishuangbanna, China; 2) screen out new efficient mosquito repellent plants as candidates for further study. MATERIALS AND METHODS: During the period August 2016 to July 2017, five field surveys were conducted in 16 villages of Xishuangbanna. A total of 81 informants (44 males and 37 females) were interviewed using semi-structured questions to collect detailed information on the plants they use to prevent mosquito bites. Ten plants with higher popularity and larger resource were collected and extracts were prepared by hydro-distillation or with petroleum ether. Extracts were tested for adult Aedes albopictus repellency using a human-bait cage. Firstly, repellency was determined as the Minimum Effective Dosage (MED) per minute at which 1% of the mosquito bite through the treated cloth. Secondly, five plant extracts with lower MEDs were tested the repellent longevity of different concentrations. RESULTS: Eighteen plants were documented as being used in traditional remedies against mosquitoes. The methods for controlling mosquitoes were diverse: direct burning was used for most plants (16 species), followed by smearing (5 species), and placing (5 species). Laboratory analyses confirmed that ten plants did exhibit mosquito repellent activity. Of them, Artemisia indica, Nicotiana tabacum, Blumea balsamifera, Vitex trifolia, and Chromolaena odorata showed good mosquito repellency with MEDs of 0.015, 0.061, 0.090, 0.090, and 0.105 mg/cm2, respectively. The protection rate provided by A. indica is also the highest among five plants. Although it provides complete protection time of only 30 min at 0.45 mg/cm2 concentration, its repellency within 2 h is not significantly different from that of DEET. CONCLUSION: Dai villagers in Xishuangbanna have a rich, diverse and scientific knowledge of plant-based mosquito repellents. Laboratory experiments screened out several plants as candidates for mosquito repellents, of which Artemisia indica was the most promising candidate plant.