Phenotype transformation in pituitary neuroendocrine tumors is a little-known and unpredictable clinical phenomenon. Previous studies have not clearly defined and systematically concluded on the causes of this rare phenomenon. Additionally, the mechanisms of phenotype transformation are not well known. We reviewed cases reported in the literature with the aim of defining phenotype transformation in pituitary neuroendocrine tumors. We present an overview of the wide spectrum of phenotype transformation and its clinical features. We also discuss findings on the potential mechanism of this rare transformation, which may be related to PC1/3, the bioactivity of secretory hormones, gene mutations and the plasticity of pituitary neuroendocrine tumors. Clinicians should be aware of this rare phenomenon and more studies on the underlying mechanisms are required.
Flexibility has become increasingly important considering the intermittency of variable renewable energy in low-carbon energy systems. Electrified transportation exhibits great potential to provide flexibility. This article analyzed and compared the flexibility values of battery electric vehicles and fuel cell electric vehicles for planning and operating interdependent electricity and hydrogen supply chains while considering battery degradation costs. A cross-scale framework involving both macro-level and micro-level models was proposed to compute the profits of flexible EV refueling/charging with battery degradation considered. Here we show that the flexibility reduction after considering battery degradation is quantified by at least 4.7% of the minimum system cost and enlarged under fast charging and low-temperature scenarios. Our findings imply that energy policies and relevant management technologies are crucial to shaping the comparative flexibility advantage of the two transportation electrification pathways. The proposed cross-scale methodology has broad implications for the assessment of emerging energy technologies with complex dynamics.
Soft millirobots have evolved into various therapeutic applications in the medical field, including for vascular dredging, cell transportation, and drug delivery, owing to adaptability to their surroundings. However, most soft millirobots cannot quickly enter, retrieve, and maintain operations in their original locations after removing the external actuation field. This study introduces a soft magnetic millirobot for targeted medicine delivery that can be transported into the body through a catheter and anchored to the tissues. The millirobot has a bilayer adhesive body with a mussel-inspired hydrogel layer and an octopus-inspired magnetic structural layer. It completes entry and retrieval with the assistance of a medical catheter based on the difference between the adhesion of the hydrogel layer in air and water. The millirobot can operate in multiple modes of motion under external magnetic fields and underwater tissue adhesion after self-unfolding with the structural layer. The adaptability and recyclability of the millirobots are demonstrated using a stomach model. Combined with ultrasound (US) imaging, operational feasibility within organisms is shown in isolated small intestines. In addition, a highly efficient targeted drug delivery is confirmed using a fluorescence imaging system. Therefore, the proposed soft magnetic millirobots have significant potential for medical applications.
Adhesives , Drug Delivery Systems , Hydrogels/chemistry , Catheters , Magnetic Phenomena
In this paper, we propose a dual-structured prior neural network model that independently restores both the amplitude and phase image using a random latent code for Fourier ptychography (FP). We demonstrate that the inherent prior information within the neural network can generate super-resolution images with a resolution that exceeds the combined numerical aperture of the FP system. This method circumvents the need for a large labeled dataset. The training process is guided by an appropriate forward physical model. We validate the effectiveness of our approach through simulations and experimental data. The results suggest that integrating image prior information with system-collected data is a potentially effective approach for improving the resolution of FP systems.
Solar and wind resources are vital for the sustainable energy transition. Although renewable potentials have been widely assessed in existing literature, few studies have examined the statistical characteristics of the inherent renewable uncertainties arising from natural randomness, which is inevitable in stochastic-aware research and applications. Here we develop a rule-of-thumb statistical learning model for wind and solar power prediction and generate a year-long dataset of hourly prediction errors of 30 provinces in China. We reveal diversified spatiotemporal distribution patterns of prediction errors, indicating that over 60% of wind prediction errors and 50% of solar prediction errors arise from scenarios with high utilization rates. The first-order difference and peak ratio of generation series are two primary indicators explaining the uncertainty distribution. Additionally, we analyze the seasonal distributions of the provincial prediction errors that reveal a consistent law in China. Finally, policies including incentive improvements and interprovincial scheduling are suggested.
Accurate evaluation of Li-ion battery (LiB) safety conditions can reduce unexpected cell failures, facilitate battery deployment, and promote low-carbon economies. Despite the recent progress in artificial intelligence, anomaly detection methods are not customized for or validated in realistic battery settings due to the complex failure mechanisms and the lack of real-world testing frameworks with large-scale datasets. Here, we develop a realistic deep-learning framework for electric vehicle (EV) LiB anomaly detection. It features a dynamical autoencoder tailored for dynamical systems and configured by social and financial factors. We test our detection algorithm on released datasets comprising over 690,000 LiB charging snippets from 347 EVs. Our model overcomes the limitations of state-of-the-art fault detection models, including deep learning ones. Moreover, it reduces the expected direct EV battery fault and inspection costs. Our work highlights the potential of deep learning in improving LiB safety and the significance of social and financial information in designing deep learning models.
Salvianolic acid B is extracted from the roots and rhizomes of Danshen (Salvia miltiorrhiza Bge., family Labiatae). It is a water-soluble, weakly acidic drug that has demonstrated antitumor and anti-inflammatory effects on various organs and tissues such as the lung, heart, kidney, intestine, bone, liver, and skin and protective effects in diseases such as depression and spinal cord injury. The mechanisms underlying the protective effects of salvianolic acid B are mainly related to its anti-inflammatory, antioxidant, anti- or pro-apoptotic, anti- or pro-autophagy, anti-fibrotic, and metabolism-regulating functions. Salvianolic acid B can regulate various signaling pathways, cells, and molecules to achieve maximum therapeutic effects. This review summarizes the safety profile, combination therapy potential, and new dosage forms and delivery routes of salvianolic acid B. Although significant research progress has been made, more in-depth pharmacological studies are warranted to identify the mechanism of action, related signaling pathways, more suitable combination drugs, more effective dosage forms, and novel routes of administration of salvianolic acid B.
ZnCdS, a metal chalcogenide solid solution, has attracted significant attention. However, two primary challenges hinder its widespread application in photocatalytic hydrogen evolution: the rapid recombination rate of photogenerated carriers and susceptibility to photo-oxidation in the aqueous environments. In this article, a facile hydrothermal route was employed for the first time to uniformly assemble SnS2 nanoparticles onto the surface of Zn0.2Cd0.8S (ZCS) nanopolyhedra. The intimate contact of two materials resulted in the formation of heterojunctions. By adjusting the content of SnS2, the hydrogen evolution reaction (HER) performance was optimized to reach up to 12170 µmol/gh, which is 1.9 times of the pristine ZCS. Notably, the photocatalyst demonstrated remarkable stability with an apparent quantum yield (AQY) of 15.5% at 420 nm. The enhanced photocatalytic performance can be attributed to the following factors: (i) The heterojunction composite, with larger surface area and more micropores, provides additional active sites and exhibits high photocatalytic activity; (ii) The internal electric field accelerates the separation of photogenerated carriers and reduces the recombination rate of electron-hole pairs; (iii) The photogenerated holes can be quickly transferred to the valence band of SnS2 and react with triethanolamine, thereby significantly reducing the photo-oxidation of ZCS. This work not only proposed a feasible route to improve the photocatalytic activity of ZCS, but also provided insights into the role of heterojunctions and the reaction mechanism.
ETHNOPHARMACOLOGICAL RELEVANCE: The dried and mature seeds of Strychnons pierriana A.W.Hill. have been called Strychnine Semen(S. Semen). It have been used in traditional Chinese medicine for nearly 400 years. In recent decades, scholars at home and abroad have widely used S. Semen in the treatment of tumor diseases, showing good anti-tumor effects. In this paper, the modern research achievements of S. Semen are reviewed, including traditional uses, phytochemistry, pharmacology, and toxicology. AIM OF THE STUDY: In recent years, the research on S. Semen has increased gradually, especially the research on its anti-tumor. This paper not only reviewed the traditional uses, chemical constituents and pharmacological activities of S. Semen, but also comprehensively listed the mechanisms of Strychnos in the treatment of different tumors, providing a review for further research and development of Strychnos resources. MATERIALS AND METHODS: A systematic review of the literature on Fuzi was performed using several resources, namely classic books on Chinese herbal medicine and various scientific databases, such as PubMed, the Web of Science, and the China Knowledge Resource Integrated databases. RESULTS: The main constituents of S. Semen include alkaloids, terpenoids, steroids, and their glycosides. Modern studies have proved that S. Semen has a wide range of pharmacological effects, including anti-inflammatory and analgesic, anti-thrombotic, myocardial cell protection, immune regulation, nerve excitation, and anti-tumor effects. Among them, the anti-tumor effect has been the focus of research in recent years. S. Semen have a certain therapeutic effect on many kinds of tumors, such as liver cancer, colon cancer, and stomach cancer in the digestive system, breast, cervical, and ovarian cancer in the reproductive system, myeloma and leukemia in the blood system, and those in the nervous system and the immune system. CONCLUSION: Strychnine has an inhibitory effect on a variety of tumors. However, modern studies of strychnine are incomplete, and more in-depth studies are needed on its stronger bioactive constituents and potential pharmacological effects. The antitumor effect of Strychnine is worth further exploration.
Alkaloids , Drugs, Chinese Herbal , Strychnine , Seeds , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Alkaloids/pharmacology , Alkaloids/therapeutic use , Medicine, Chinese Traditional , Analgesics , Phytochemicals/pharmacology , Phytochemicals/therapeutic use , Ethnopharmacology , Plant Extracts/pharmacology , Plant Extracts/therapeutic use
Celastrol, triptolide and triptonide are the most significant active ingredients of Tripterygium wilfordii Hook F (TWHF). In 2007, the 'Cell' journal ranked celastrol, triptolide, artemisinin, capsaicin and curcumin as the five natural drugs that can be developed into modern medicinal compounds. In this review, we collected relevant data from the Web of Science, PubMed and China Knowledge Resource Integrated databases. Some information was also acquired from government reports and conference papers. Celastrol, triptolide and triptonide have potent pharmacological activity and evident anti-cancer, anti-tumor, anti-obesity and anti-diabetes effects. Because these compounds have demonstrated unique therapeutic potential for acute and chronic inflammation, brain injury, vascular diseases, immune diseases, renal system diseases, bone diseases and cardiac diseases, they can be used as effective drugs in clinical practice in the future. However, celastrol, triptolide and triptonide have certain toxic effects on the liver, kidney, cholangiocyte heart, ear and reproductive system. These shortcomings limit their clinical application. Suitable combination therapy, new dosage forms and new routes of administration can effectively reduce toxicity and increase the effect. In recent years, the development of different targeted drug delivery formulations and administration routes of celastrol and triptolide to overcome their toxic effects and maximise their efficacy has become a major focus of research. However, in-depth investigation is required to elucidate the mechanisms of action of celastrol, triptolide and triptonide, and more clinical trials are required to assess the safety and clinical value of these compounds.
Diterpenes , Neoplasms , Phenanthrenes , Triterpenes , Humans , Diterpenes/pharmacology , Phenanthrenes/pharmacology , Epoxy Compounds/pharmacology
BACKGROUND: Primary Sjögren's Syndrome (pSS) is an autoimmune disease. It can damage the salivary and lacrimal glands and is characterized by dry mouth and eye symptoms, which seriously affects people's normal life. Both modern medicine and Traditional Chinese medicine (TCM) have certain effects in treating SS. However, there are different theories about which treatment is more appropriate. OBJECTIVE: The aim of this research was to compare the efficacy and safety of TCM to Western Medicine in the treatment of pSS. METHODS: We collected randomized controlled trials (RCTs) of TCM, integrating traditional Chinese and Western medicine for the treatment of pSS in Chinese and foreign databases. RESULTS: A total of 13 articles were eventually included with 780 cases. The final results were expressed in odds ratio (OR), mean difference (MD), 95% confidence interval (CI), and overall effect (z). The effective rate was 86.03% in the TCM group and 67.75% in the western medicine group. Results of the effective rate were OR = 3.57; 95% CI = 2.44-5.23; z = 6.56; pï¼0.00001, ESR were MD = -6.90; 95% CI = -10.76--3.05; z = 3.51; p = 0.0005ï¼0.05, Schirmer's test were MD = 3.39; 95% CI = 1.92-4.86; z = 4.5; pï¼0.00001, salivary flow were MD = 0.62; 95% CI = 0.16-1.07; z = 2.63; p = 0.009ï¼0.05, and adverse reactions were OR = 0.35; 95% CI = 0.17-0.72; z = 2.84; p = 0.004. CONCLUSION: TCM has a remarkable effect on the treatment of pSS. Among them Yiguanjian decoction and Liuwei Dihuang decoction were effective prescriptions with the highest frequency of application. Rehmanniae Radix (Rehmannia glutinosa Libosch.) and Ophiopogonis Radix (Ophiopogon japonicus (L. f.) Ker-Gawl.) were the most frequently used TCM.
Rehmannia , Sjogren's Syndrome , Humans , Medicine, Chinese Traditional/methods , Sjogren's Syndrome/drug therapy , Plant Extracts
ETHNOPHARMACOLOGICAL RELEVANCE: The lateral root of Aconitum carmichaelii Debx is known as Fuzi in Chinese. It is traditionally valued and used for dispelling cold, relieving pain effects, restoring 'Yang,' and treating shock despite its high toxicity. This review aims to provide comprehensive information on the chemical composition, pharmacological research, preparation, and compatibility of Fuzi to help reduce its toxicity and increase its efficiency, based on the scientific literature. In addition, this review will establish a new foundation for further studies on Fuzi. MATERIALS AND METHODS: A systematic review of the literature on Fuzi was performed using several resources, namely classic books on Chinese herbal medicine and various scientific databases, such as PubMed, the Web of Science, and the China Knowledge Resource Integrated databases. RESULTS: Fuzi extracts contain diester-type alkaloids, monoester-type alkaloids, other types of alkaloids, and non-alkaloids types, and have various pharmacological activities, such as strong heart effect, effect on blood vessels, and antidepressant, anti-diabetes, anti-inflammatory, pain-relieving, antitumor, immunomodulatory, and other therapeutic effects. However, these extracts can also lead to various toxicities such as cardiotoxicity, neurotoxicity, reproductive toxicity, hepatotoxicity, and embryonic toxicity. In vivo and in vitro experiments have demonstrated that different processing methods and suitable compatibility with other herbs can effectively reduce the toxicities and increase the efficiency of Fuzi. CONCLUSION: The therapeutic potential of Fuzi has been demonstrated in conditions, such as heart failure, various pains, inflammation, and tumors, which is attributed to the diester-type alkaloids, monoester-type alkaloids, other types of alkaloids, and non-alkaloid types. In contrast, they are also toxic components. Proper processing and suitable compatibility can effectively reduce toxicity and increase the efficiency of Fuzi. Thus more pharmacological and toxicological mechanisms on main active compounds are necessary to be explored.
Aconitum , Diterpenes , Drugs, Chinese Herbal , Aconitum/chemistry , Anti-Inflammatory Agents , Diterpenes/chemistry , Drugs, Chinese Herbal/chemistry
Purpose: Diabetic macular edema (DME) is the leading cause of vision loss and blindness among working-age adults. Although current intravitreal anti-vascular endothelial growth factor (VEGF) therapies improve vision for many patients with DME, approximately half do not achieve the visual acuity required to drive. We therefore sought additional approaches to resolve edema and improve vision for these patients. Methods: We explored direct agonists of Tie2, a receptor known to stabilize vasculature and prevent leakage. We identified a multivalent PEG-Fab conjugate, Tie2.1-hexamer, that oligomerizes Tie2 and drives receptor activation and characterized its activities in vitro and in vivo. Results: Tie2.1-hexamer normalized and stabilized intercellular junctions of stressed endothelial cell monolayers in vitro, suppressed vascular leak in mice under conditions where anti-VEGF alone was ineffective, and demonstrated extended ocular exposure and robust pharmacodynamic responses in non-human primates. Conclusions: Tie2.1-hexamer directly activates the Tie2 pathway, reduces vascular leak, and is persistent within the vitreal humor. Translational Relevance: Our study presents a promising potential therapeutic for the treatment of DME.
Diabetes Mellitus , Diabetic Retinopathy , Macular Edema , Mice , Animals , Macular Edema/drug therapy , Macular Edema/etiology , Diabetic Retinopathy/drug therapy , Endothelial Growth Factors/therapeutic use , Visual Acuity , Vision Disorders/complications , Vision Disorders/drug therapy , Blindness/complications
Axonal projection conveys neural information. The divergent and diverse projections of individual neurons imply the complexity of information flow. It is necessary to investigate the relationship between the projection and functional information at the single neuron level for understanding the rules of neural circuit assembly, but a gap remains due to a lack of methods to map the function to whole-brain projection. Here an approach is developed to bridge two-photon calcium imaging in vivo with high-resolution whole-brain imaging based on sparse labeling with the genetically encoded calcium indicator GCaMP6. Reliable whole-brain projections are captured by the high-definition fluorescent micro-optical sectioning tomography (HD-fMOST). A cross-modality cell matching is performed and the functional annotation of whole-brain projection at the single-neuron level (FAWPS) is obtained. Applying it to the layer 2/3 (L2/3) neurons in mouse visual cortex, the relationship is investigated between functional preferences and axonal projection features. The functional preference of projection motifs and the correlation between axonal length in MOs and neuronal orientation selectivity, suggest that projection motif-defined neurons form a functionally specific information flow, and the projection strength in specific targets relates to the information clarity. This pipeline provides a new way to understand the principle of neuronal information transmission.
Neurons , Visual Cortex , Animals , Mice , Neurons/physiology , Brain , Visual Cortex/physiology , Axons/physiology , Brain Mapping/methods
The rapid development of distributed photovoltaic (PV) systems poses great challenges to the integration capability of distribution networks. Traditionally, the transfer capacity of power distribution equipment is calculated as the maximum loading that prevents overheating under the assumption of extreme weather conditions. Dynamic thermal rating (DTR), which evaluates equipment capacity based on real-time weather conditions, could enhance the transfer capacity to improve distributed PV integration. Through case studies in Texas, Switzerland, and China, we show that the application of DTR on power distribution equipment could increase installed PV capacities by 15%-27% and improve net revenues by 4%-27%. We also find that the application of DTR would be positively affected by climate change and is more profitable under the PV policies with higher tariffs for the surplus generation fed into the grid. Compared to energy storage systems, DTR provides a more cost-competitive option to enhance the integration capability of distribution networks.
Background: Holt-Oram syndrome (HOS) is an autosomal dominant disorder caused by mutations of TBX5 gene. Case presentation: We report a fetus with HOS diagnosed sonographically at 23 weeks of gestation. The fetal parents are non-consanguineous. The fetus exhibited short radius and ulna, inability to supinate the hands, absence of the right thumb, and heart ventricular septal defect (VSD), while the fetal father exhibited VSD and short radius and ulna only. Fetal brother had cubitus valgus and thumb adduction, except for VSD, short radius and ulna. The pregnancy was terminated. Whole-exome sequencing (WES) revealed a novel mutation in the TBX5 (c.510+1G>A) in the fetus inherited from the father. The variant (c.510+1G>A) occurs at splice donor and may alter TBX5 gene function by impact on splicing. It was not previously reported in China. Conclusion: Our case reported a novel mutation in TBX5, which expanded the known genetic variants associated with HOS.
Deep neural networks (DNNs) have been used as a new method for nanophotonic inverse design. However, DNNs need a huge dataset to train if we need to select materials from the material library for the inverse design. This puts the DNN method into a dilemma of poor performance with a small training dataset or loss of the advantage of short design time, for collecting a large amount of data is time consuming. In this work, we propose a multi-scenario training method for the DNN model using imbalanced datasets. The imbalanced datasets used by our method is nearly four times smaller compared with other training methods. We believe that as the material library increases, the advantages of the imbalanced datasets will become more obvious. Using the high-precision predictive DNN model obtained by this new method, different multilayer nanoparticles and multilayer nanofilms have been designed with a hybrid optimization algorithm combining genetic algorithm and gradient descent optimization algorithm. The advantage of our method is that it can freely select discrete materials from the material library and simultaneously find the inverse design of discrete material type and continuous structural parameters of the nanophotonic devices.
BACKGROUND: Liver cancer ranks the top four malignant cancer type worldwide, which needs effective and safe treatment. Ferroptosis is a novel form of regulated cell death driven by iron-dependent lipid peroxidation and has been regarded as a promising therapeutic target for cancers. In this work, we aimed to study the effects of anesthetic ketamine on proliferation and ferroptosis of liver cancer. METHODS: Cell viability and proliferation were detected by cell counting kit 8 (CCK-8), colony formation, and 5-ethynyl-2'-deoxyuridine (EdU) assay. Ferroptosis was determined by levels of Fe2+, lipid reactive oxygen species (ROS), and malondialdehyde (MDA). RNA levels of lncPVT1, miR-214-3p, and glutathione peroxidase 4 (GPX4) were checked by real-time PCR assay. Clinical liver tumor samples were collected to detect the levels of long noncoding RNA lncPVT1, miR-214-3p, and GPX4, and their correlation was evaluated by Pearson comparison test. Luciferase reporter gene assay and RNA pulldown were conducted to determine the binding between lncPVT1, miR-214-3p, and GPX4 3'UTR. RESULTS: Ketamine significantly suppressed viability and proliferation of liver cancer cells both in vitro and in vivo, as well as stimulated ferroptosis, along with decreased expression of lncPVT1 and GPX4. LncPVT1 directly interacted with miR-214-3p to impede its role as a sponge of GPX4. Depletion of lncPVT1 accelerated the ferroptosis of live cancer cells, whereas miR-214-3p inhibition and GPX4 overexpression reversed this effect. Ketamine-induced cell growth suppression and ferroptosis were also suppressed by miR-214-3p inhibition and GPX4 overexpression. CONCLUSION: In this work, we determined that ketamine suppressed viability of liver cancer cells and induced ferroptosis and identified the possible regulatory mechanism of lncPVT1/miR-214-3p/GPX4 axis.
Cell Survival/drug effects , Ferroptosis/drug effects , Ketamine/pharmacology , Liver Neoplasms/drug therapy , Animals , Cell Line, Tumor , Cell Proliferation/drug effects , Hep G2 Cells , Humans , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Mice, Inbred BALB C , Mice, Nude , MicroRNAs/genetics , Phospholipid Hydroperoxide Glutathione Peroxidase/genetics , RNA, Long Noncoding/genetics , Xenograft Model Antitumor Assays
BACKGROUND: CYP21A2 gene mutations may all cause reduction or loss of 21-hydroxylase activity, leading to development of congenital adrenal hyperplasia (CAH) with different clinical phenotypes. For families with CAH children, genetic testing of the parents and genetic counseling are recommended to assess the risk of recurrence. CASE SUMMARY: We report a case of CAH with a high suspicion before delivery. The risk of the child suffering from CAH during the pregnancy had been underestimated due to the deviation of genetic counseling and genetic testing results. Our report confirmed a CYP21A2 homozygous deletion in this case, CYP21A2 heterozygous deletion in the mother, and a rare 2+0 CYP21A2 deletion in the father. CONCLUSION: It is important to analyze the distribution of CYP21A2 gene in the two alleles of parents of children with CAH.
AIM: This study was aimed to identify the potentially pathogenic gene variants that contribute to the etiology of the autosomal recessive renal tubular dysgenesis (RTD) in the aborted fetus. METHODS: Illumina infinium global screening array was used to analyze chromosome karyotype of the aborted fetus. The exomes of the aborted fetus and his parents were sequenced using the whole exome sequencing technology. The resulting variants from whole exome sequencing were filtered by basic and advanced biological information analysis and the candidate mutation was verified by Sanger sequencing. RESULTS: Trisomy in chromosome 10 was found in the aborted fetus. The exon heterozygous variant of c.963T > A (p.Y321X) (nonsense mutation) and intron heterozygous variant of c.492 + 1G > A (splicing site mutation) in REN was first identified and validated by Sanger sequencing. Moreover, the exon heterozygous variant of c.963T > A (p.Y321X) and intron heterozygous variant of c.492 + 1G > A was from the mother and father, respectively. CONCLUSION: Our results reported the novel exon heterozygous variant of c.963T > A (p.Y321X) and intron heterozygous variant of c.492 + 1G > A in REN may contribute to autosomal recessive RTD, expanding our understanding of the causally relevant mutations for this disorder.
Urogenital Abnormalities , Heterozygote , Humans , Kidney Tubules, Proximal/abnormalities , Mutation , Pedigree , Urogenital Abnormalities/genetics , Exome Sequencing
