Search

Biodegradable magnesium‐based scaffolds present outstanding potential to revolutionize the treatment of coronary artery diseases, in which full recovery of arteries without long‐term irritation of implants is anticipated for averting adverse events associated with the permanent stents. However, overfast degradation of magnesium (Mg) alloys obstructs their extensive applications in terms of early structural failure and impaired biocompatibility. Herein, a facile copper‐incorporated coating system through nonaqueous phase synthesis of polydopamine is developed to facilitate Cu(II) capture along with robust film deposited on easily corrodible Mg, which subsequently enables sustained Cu(II) elution. It remarkably enhances corrosion resistance and impedes Mg degradation, which also contributes to improved, superior cytocompatibility, and abolished hemolysis. Moreover, through simultaneous control of Cu(II) and Mg(II) release to modulate the local microenvironment, a synergistic biochemical effect on desirable vascular cell selectivity is triggered for boosted endothelial cell viability and suppressed smooth muscle cell. Stent implantation into rabbit abdominal aorta thus exhibits accelerated re‐endothelialization completed in a week, and enhanced biological outcomes, alleviated complications and prolonged structural durability in 3‐month follow‐up. Collectively, this study opens up an alternative route of deploying a multifunctional surface modification strategy tailoring active interplay with the Mg matrix for better outcomes of next‐generation bioresorbable vascular stents. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the efficiency of low-level laser therapy on the distal osseous defects of the mandibular second molar (M2) after the adjacent impacted third molar (M3) extraction. Methods. A total of 59 clinic cases were screened out, whose M3 were impacted and the distal alveolar bone of M2 had been destroyed horizontally. They were randomly divided into 2 groups based on whether they would have laser irradiation or not after M3 extraction. Then, postoperative complications of the 2 groups were compared. The alveolar bone level distal to M2 was established before and 3 to 6 months after M3 extraction by radiographic evaluation, which was compared between two groups. Results. The incidence of severe pain and mouth-opening limitation was significantly lower in the LLLT group than that in the control group. The amount of bone formation in the LLLT group was higher than that in the control group 3 months after the operation, and the difference was statistically significant. But the difference was not statistically significant 6 months after surgery. Conclusion. LLLT may alleviate postoperative complications and improve early osteogenesis. It is a viable option for use in the treatment of osseous defects distal to mandibular second molars following extraction of impacted third molars. [ABSTRACT FROM AUTHOR]

Introduction: Traditional cancer therapy has many disadvantages such as low selectivity and high toxicity of chemotherapy, as well as insufficient efficacy of targeted therapy. To enhance the cytotoxic effect and targeting ability, while reducing the toxicity of antitumor drugs, an antibody drug conjugate (ADC) was developed to deliver small molecular cytotoxic payloads directly to tumor cells by binding to specific antibodies via linkers. Method: By reviewing published literature and the current progress of ADCs, we aimed to summarize the basic characteristics, clinical progress, and challenges of ADCs to provide a reference for clinical practice and further research. Results: ADC is a conjugate composed of three fundamental components, including monoclonal antibodies, cytotoxic payloads, and stable linkers. The mechanisms of ADC including the classical internalization pathway, antitumor activity of antibodies, bystander effect, and non‐internalizing mechanism. With the development of new drugs and advances in technology, various ADCs have achieved clinical efficacy. To date, nine ADCs have received US Food and Drug Administration (FDA) approval in the field of hematologic tumors and solid tumors, which have become routine clinical treatments. Conclusion: ADC has changed traditional treatment patterns for cancer patients, which enable the same treatment for pancreatic cancer patients and promote individualized precision treatment. Further exploration of indications could focus on early‐stage cancer patients and combined therapy settings. Besides, the mechanisms of drug resistance, manufacturing techniques, optimized treatment regimens, and appropriate patient selection remain the major topics. [ABSTRACT FROM AUTHOR]

Objectives: Recent studies showed prolonged survival for advanced epidermal growth factor receptor (EGFR)‐mutant non‐small cell lung cancer (NSCLC) patients treated with both monotherapies and combined therapies. However, high costs limit clinical applications. Thus, we conducted this cost‐effectiveness analysis to explore an optimal first‐line treatment for advanced EGFR‐mutant NSCLC patients. Materials and Methods: Survival data were extracted from six clinical trials, including ARCHER1050 (dacomitinib vs. gefitinib); FLAURA (osimertinib vs. gefitinib/erlotinib); JO25567 and NEJ026 (bevacizumab +erlotinib vs. erlotinib); NEJ009 (gefitinib +chemotherapy vs. gefitinib); and NCT02148380 (gefitinib +chemotherapy vs. gefitinib vs. chemotherapy) trials. Cost‐related data were obtained from hospitals and published literature. The effect parameter (quality‐adjusted life year [QALY]) was the reflection of both survival and utility. Incremental cost‐effectiveness ratio (ICER), average cost‐effectiveness ratio (ACER), and net benefit were calculated, and the willingness‐to‐pay (WTP) threshold was set at $30828/QALY from the perspective of the Chinese healthcare system. Sensitivity analysis was performed to explore the stability of results. Results: We compared treatment groups with control groups in each trial. ICERs were $1897750.74/QALY (ARCHER1050), $416560.02/QALY (FLAURA), ‐$477607.48/QALY (JO25567), ‐$464326.66/QALY (NEJ026), ‐$277121.22/QALY (NEJ009), ‐$399360.94/QALY (gefitinib as comparison, NCT02148380), and ‐$170733.05/QALY (chemotherapy as comparison, NCT02148380). Moreover, ACER and net benefit showed that the combination of EGFR‐TKI with chemotherapy and osimertinib was of more economic benefit following first‐generation EGFR‐TKIs. Sensitivity analyses showed that the impact of utilities and monotherapy could be cost‐effective with a 50% cost reduction. Conclusion: First‐generation EGFR‐TKI therapy remained the most cost‐effective treatment option for advanced EGFR‐mutant NSCLC patients. Our results could serve as both a reference for both clinical practice and the formulation of medical insurance reimbursement. [ABSTRACT FROM AUTHOR]

Key points: The pparab subtype in zebrafish is much more highly expressed in tissues with high oxidative activity than pparaa.The pparab deficiency in zebrafish reduces fatty acid β‐oxidation both in liver and muscle, illustrating its functional homology as a mammalian peroxisome proliferator‐activated receptor α (PPARα).pparab deficiency promotes metabolic reprogramming by increasing glucose utilization and inhibiting amino acid breakdown.The present study brings new insights into the comprehensive regulatory roles of PPARα in the cellular fuel selection and provides a valuable animal model for PPARα studies from a viewpoint of comparative physiology. Dysfunction of lipid metabolism is involved in the pathogenesis of several chronic metabolic diseases. Peroxisome proliferator‐activated receptor α (PPARα) is essential for normal metabolic homeostasis and, in particular, for the regulation of fatty acid β‐oxidation (FAO). However, little is known about its regulation roles in systemic nutrient metabolism. To explore the underlying modulation role of PPARα in metabolic homeostasis, we generated a pparab‐knockout zebrafish (Danio rerio) model. The pparab mutants demonstrated lower expression of key enzymes involved in FAO, as well as lower mitochondrial and peroxisomal FAO in tissues, which was associated with lipid accumulation in liver and visceral mass. Conversely, glucose utilization was higher because they demonstrated lower blood glucose and tissue glycogen concentrations, as well as activation of the phosphoinositide 3‐kinase/AKT pathway. In addition, pparab‐deficient zebrafish demonstrated activation of AKT/mammalian target of rapamycin signalling and higher protein content, implying greater protein synthesis and/or lower amino acid breakdown. These data clearly revealed that pparab deletion reduces FAO but increases glucose utilization and protein deposition to maintain energy homeostasis. The present study provides new insights into the comprehensive regulatory role of PPARα in systemic energy metabolism in fish, and this pparab‐deficient zebrafish also constitutes a valuable model for investigating the functions of PPARα in mammals from comparative physiology aspects. Key points: The pparab subtype in zebrafish is much more highly expressed in tissues with high oxidative activity than pparaa.The pparab deficiency in zebrafish reduces fatty acid β‐oxidation both in liver and muscle, illustrating its functional homology as a mammalian peroxisome proliferator‐activated receptor α (PPARα).pparab deficiency promotes metabolic reprogramming by increasing glucose utilization and inhibiting amino acid breakdown.The present study brings new insights into the comprehensive regulatory roles of PPARα in the cellular fuel selection and provides a valuable animal model for PPARα studies from a viewpoint of comparative physiology. [ABSTRACT FROM AUTHOR]

L‐carnitine is a multi‐functional nutrient which plays a leading role in fatty acid metabolism in mammals and other eukaryotes. Its main physiological function is to promote fatty acid β‐oxidation to produce energy, which reduces body fat content and improves body weight without affecting moisture content in whole body and muscle. In recent years, its dietary supplementation in aquaculture nutrition has been studied in different cultured species. It has been proved that L‐carnitine can improve growth and increase lipid utilization rate in some aquatic animals. However, such beneficial effects of dietary L‐carnitine are limited or absent in other species. The reasons for the conflicting results obtained on L‐carnitine functions in aquatic animals need to be elucidated. This review explores comprehensively the different physiological functions of L‐carnitine in various aquatic animals. In the end, research strategies are provided to elucidate the existing conflicts on dietary L‐carnitine application in aquaculture nutrition in order to promote its utilization in aquatic feed industry. [ABSTRACT FROM AUTHOR]

Key points: In a cold environment, mammals increase their food intake while fish decrease or stop feeding. However, the physiological value of fasting during cold resistance in fish is currently unknown.Fasting for more than 48 h enhanced acute cold resistance in zebrafish, which correlated with lipid catabolism and cell damage attenuation.Lipid catabolism and autophagy were necessary for cold resistance in fish and the inhibition of mitochondrial fatty acid β‐oxidation or autophagy weakened the fasting‐induced cold resistance.Repression of mechanistic target of rapamycin (mTOR) signalling pathway by rapamycin largely mimicked the beneficial effects of fasting in promoting cold resistance, suggesting mTOR signalling may be involved in the fasting‐induced cold resistance in fish.Our study demonstrates that fasting may be a protective strategy for fish to survive under cold stress. In cold environments, most homeothermic animals increase their food intake to supply more energy to maintain body temperature, whereas most poikilothermic animals such as fishes decrease or even stop feeding under cold stress. However, the physiological value of fasting during cold resistance in poikilotherms has not been explained. Here, we show that moderate fasting largely enhanced cold resistance in fish. By using pharmacological (fenofibrate, mildronate, chloroquine and rapamycin) and nutritional approaches (fatty acids diets and amino acids diets) in wild‐type or specific gene knock‐out zebrafish models (carnitine palmitoyltransferase‐1b‐deficient strain, CPT1b−/−, or autophagy‐related protein 12‐deficient strain, ATG12−/−), we verified that fasting‐stimulated lipid catabolism and autophagy played essential roles in the improved cold resistance. Moreover, suppression of the mechanistic target of rapamycin (mTOR) pathway by using rapamycin mostly mimicked the beneficial effects of fasting in promoting cold resistance as either the physiological phenotype or transcriptomic pattern. However, these beneficial effects were largely reduced when the mTOR pathway was activated through high dietary leucine supplementation. We conclude that fasting helps fish to resist cold stress by modulating lipid catabolism and autophagy, which correlates with the mTOR signalling pathway. Therefore, fasting can act as a protective strategy of fish in resisting coldness. Key points: In a cold environment, mammals increase their food intake while fish decrease or stop feeding. However, the physiological value of fasting during cold resistance in fish is currently unknown.Fasting for more than 48 h enhanced acute cold resistance in zebrafish, which correlated with lipid catabolism and cell damage attenuation.Lipid catabolism and autophagy were necessary for cold resistance in fish and the inhibition of mitochondrial fatty acid β‐oxidation or autophagy weakened the fasting‐induced cold resistance.Repression of mechanistic target of rapamycin (mTOR) signalling pathway by rapamycin largely mimicked the beneficial effects of fasting in promoting cold resistance, suggesting mTOR signalling may be involved in the fasting‐induced cold resistance in fish.Our study demonstrates that fasting may be a protective strategy for fish to survive under cold stress. [ABSTRACT FROM AUTHOR]

The article presents the process to accomplish the use of aldol reactions on pepsin catalysts for the synthesis of vicinaldiol compounds and describes the chemical equations of the process.

Review: 86 refs. [ABSTRACT FROM AUTHOR]