Effect of Serotonin (5-Hydroxytryptamine) on Follicular Development in Porcine.

5-Hydroxytryptamine (5-HT) is an inhibitory neurotransmitter widely distributed in mammalian tissues, exerting its effects through binding to various receptors. It plays a crucial role in the proliferation of granulosa cells (GCs) and the development of follicles in female animals, however, its effect on porcine follicle development is not clear. The aim of this study is to investigate the expression of 5-HT and its receptors in various parts of the pig ovary, as well as the effect of 5-HT on porcine follicular development by using ELISA, quantitative real-time PCR (qPCR) and EdU assays. Firstly, we examined the levels of 5-HT and its receptors in porcine ovaries, follicles, and GCs. The findings revealed that the expression of different 5-HT receptors varied among follicles of different sizes. To investigate the relationship between 5-HT and its receptors, we exposed the GCs to 5-HT and found a decrease in 5-HT receptor expression compared to the control group. Subsequently, the treatment of GCs with 0.5 µM, 5 µM, and 50 µM 5-HT showed an increase in the expression of cell cycle-related genes, and EdU results indicated cell proliferation after the 0.5 µM 5-HT treatment. Additionally, the expression of genes involved in E2 synthesis was examined after the treatment of granulosa cells with 0.5 µM 5-HT. The results showed that CYP19A1 and HSP17ß1 expression was decreased. These results suggest that 5-HT might affect the development of porcine follicle by promoting the proliferation of GCs and inhibiting the synthesis of estrogen. This provides a new finding for exploring the effect of 5-HT on follicular development, and lays a foundation for further research on the mechanism of 5-HT in follicles.

Schisandrin B alleviates testicular inflammation and Sertoli cell apoptosis via AR-JNK pathway.

Bacterial testicular inflammation is one of the important causes of male infertility. Using plant-derived compounds to overcome the side effects of antibiotics is an alternative treatment strategy for many diseases. Schizandrin B (SchB) is a bioactive compound of herbal medicine Schisandra chinensis which has multiple pharmacological effects. However its effect and the mechanism against testicular inflammation are unknown. Here we tackled these questions using models of lipopolysaccharide (LPS)-induced mice and -Sertoli cells (SCs). Histologically, SchB ameliorated the LPS-induced damages of the seminiferous epithelium and blood-testicular barrier, and reduced the production of pro-inflammatory mediators in mouse testes. Furthermore, SchB decreased the levels of pro-inflammatory mediators and inhibited the nuclear factor kB (NF-κB) and MAPK (especially JNK) signaling pathway phosphorylation in LPS-induced mSCs. The bioinformatics analysis based on receptor prediction and the molecular docking was further conducted. We targeted androgen receptor (AR) and illustrated that AR might bind with SchB in its function. Further experiments indicate that the AR expression was upregulated by LPS stimulation, while SchB treatment reversed this phenomenon; similarly, the expression of the JNK-related proteins and apoptotic-related protein were also reversed after AR activator treatment. Together, SchB mitigates LPS-induced inflammation and apoptosis by inhibiting the AR-JNK pathway.

Design and performance investigation of metamaterial-inspired dual band antenna for WBAN applications.

This paper presents the design and analysis of a metamaterial-based compact dual-band antenna for WBAN applications. The antenna is designed and fabricated on a 0.254 mm thick semi-flexible substrate, RT/Duroid® 5880, with a relative permittivity of 2.2 and a loss tangent of 0.0009. The total dimensions of the antenna are 0.26λo×0.19λo×0.002λo, where λo corresponds to the free space wavelength at 2.45 GHz. To enhance overall performance and isolate the antenna from adverse effects of the human body, it is backed by a 2×2 artificial magnetic conductor (AMC) plane. The total volume of the AMC integrated design is 0.55λo×0.55λo×0.002λo. The paper investigates the antenna's performance both with and without AMC integration, considering on- and off-body states, as well as various bending conditions in both E and H-planes. Results indicate that the AMC-integrated antenna gives improved measured gains of 6.61 dBi and 8.02 dBi, with bandwidths of 10.12% and 7.43% at 2.45 GHz and 5.80 GHz, respectively. Furthermore, the AMC integrated antenna reduces the specific absorption rate (SAR) to (>96%) and (>93%) at 2.45 GHz and 5.80 GHz, meeting FCC requirements for low SAR at both frequencies when placed in proximity to the human body. CST Microwave Studio (MWS) and Ansys High-Frequency Structure Simulation (HFSS), both full-wave simulation tools, are utilized to evaluate the antenna's performance and to characterize the AMC unit cell. The simulated and tested results are in mutual agreement. Due to its low profile, high gain, adequate bandwidth, low SAR values, and compact size, the AMC integrated antenna is considered suitable for WBAN applications.

Role of Comprehensive Vestibular Rehabilitation Based on Virtual Reality Technology in Residual Symptoms After Canalith Repositioning Procedure.

BACKGROUND:  We aimed to explore the role of comprehensive vestibular rehabilitation based on virtual reality (VR) technology in residual symptoms after canalith repositioning procedure. METHODS:  A total of 124 patients, who were diagnosed with benign paroxysmal positional vertigo from September 2020 to July 2023 and had residual symptoms 24 hours after the canalith repositioning procedure, were selected as the subjects. They were randomly divided into a normal control (NC) group, a Cawthorne-Cooksey exercise group (n=41), a Brandt-Daroff exercise group (n=41), and a VR group (n=42). The NC group received no intervention, the Cawthorne-Cooksey exercise group underwent Cawthorne-Cooksey exercise, the Brandt-Daroff exercise group was subjected to Brandt-Daroff exercise, and the VR group was given comprehensive vestibular rehabilitation based on VR technology. RESULTS:  After treatment, the Dizziness Handicap Inventory (DHI) and vestibular symptom index (VSI) scores of the virtual reality (VR), Cawthorne-Cooksey exercise, and Brandt-Daroff exercise groups were significantly lower than those of the NC group (P <.05). The scores of the VR group were lower than those of the Cawthorne-Cooksey exercise and Brandt-Daroff exercise groups (P < .05). The abnormality rates of ocular vestibular evoked myogenic potentials (oVEMP) and cervical vestibular evoked myogenic potentials (cVEMP) in VR, Cawthorne-Cooksey exercise, and Brandt-Daroff exercise groups were lower than those of the NC group (P <05). The rates of the VR group were lower than those of the Cawthorne-Cooksey exercise and Brandt-Daroff exercise groups (P <05). CONCLUSION:  Comprehensive vestibular rehabilitation based on VR technology can cure the residual symptoms after the canalith repositioning procedure, reduce the abnormality rates of oVEMP and cVEMP, and reconstruct the balance ability.

Preclinical characterization of [18F]D2-LW223: an improved metabolically stable PET tracer for imaging the translocator protein 18 kDa (TSPO) in neuroinflammatory rodent models and non-human primates.

Positron emission tomography (PET) targeting translocator protein 18 kDa (TSPO) can be used for the noninvasive detection of neuroinflammation. Improved in vivo stability of a TSPO tracer is beneficial for minimizing the potential confounding effects of radiometabolites. Deuteration represents an important strategy for improving the pharmacokinetics and stability of existing drug molecules in the plasma. This study developed a novel tracer via the deuteration of [18F]LW223 and evaluated its in vivo stability and specific binding in neuroinflammatory rodent models and nonhuman primate (NHP) brains. Compared with LW223, D2-LW223 exhibited improved binding affinity to TSPO. Compared with [18F]LW223, [18F]D2-LW223 has superior physicochemical properties and favorable brain kinetics, with enhanced metabolic stability and reduced defluorination. Preclinical investigations in rodent models of LPS-induced neuroinflammation and cerebral ischemia revealed specific [18F]D2-LW223 binding to TSPO in regions affected by neuroinflammation. Two-tissue compartment model analyses provided excellent model fits and allowed the quantitative mapping of TSPO across the NHP brain. These results indicate that [18F]D2-LW223 holds significant promise for the precise quantification of TSPO expression in neuroinflammatory pathologies of the brain.

Advances in Clinical Therapies for Huntington's Disease and the Promise of Multi-Targeted/Functional Drugs Based on Clinicaltrials.gov.

Huntington's disease (HD) is a dominantly inherited neurodegenerative disorder characterized by a triad of motor, cognitive, and psychiatric problems. Caused by CAG repeat expansion in the huntingtin gene (HTT), the disease involves a complex network of pathogenic mechanisms, including synaptic dysfunction, impaired autophagy, neuroinflammation, oxidative damage, mitochondrial dysfunction, and extrasynaptic excitotoxicity. Although current therapies targeting the pathogenesis of HD primarily aim to reduce mHTT levels by targeting HTT DNA, RNA, or proteins, these treatments only ameliorate downstream pathogenic effects. While gene therapies, such as antisense oligonucleotides, small interfering RNAs and gene editing, have emerged in the field of HD treatment, their safety and efficacy are still under debate. Therefore, pharmacological therapy remains the most promising breakthrough, especially multi-target/functional drugs, which have diverse pharmacological effects. This review summarizes the latest progress in HD drug development based on clinicaltrials.gov search results (Search strategy: key word "Huntington's disease" in HD clinical investigational drugs registered as of December 31, 2023), and highlights the key role of multi-target/functional drugs in HD treatment strategies.

Sphingosine d18:1 promotes nonalcoholic steatohepatitis by inhibiting macrophage HIF-2α.

Non-alcoholic steatohepatitis (NASH) is a severe type of the non-alcoholic fatty liver disease (NAFLD). NASH is a growing global health concern due to its increasing morbidity, lack of well-defined biomarkers and lack of clinically effective treatments. Using metabolomic analysis, the most significantly changed active lipid sphingosine d18:1 [So(d18:1)] is selected from NASH patients. So(d18:1) inhibits macrophage HIF-2α as a direct inhibitor and promotes the inflammatory factors secretion. Male macrophage-specific HIF-2α knockout and overexpression mice verified the protective effect of HIF-2α on NASH progression. Importantly, the HIF-2α stabilizer FG-4592 alleviates liver inflammation and fibrosis in NASH, which indicated that macrophage HIF-2α is a potential drug target for NASH treatment. Overall, this study confirms that So(d18:1) promotes NASH and clarifies that So(d18:1) inhibits the transcriptional activity of HIF-2α in liver macrophages by suppressing the interaction of HIF-2α with ARNT, suggesting that macrophage HIF-2α may be a potential target for the treatment of NASH.

A cavity induced mode hybridization plasmonic sensor for portable detection of exosomes.

Exosomes have been considered as promising biomarkers for cancer diagnosis due to their abundant information from originating cells. However, sensitive and reliable detection of exosomes is still facing technically challenges due to the lack of a sensing platform with high sensitivity and reproducibility. To address the challenges, here we propose a portable surface plasmon resonance (SPR) sensing of exosomes with a three-layer Au mirror/SiO2 spacer/Au nanohole sensor, fabricated by an economical polystyrene nanosphere self-assembly method. The SiO2 spacer can act as an optical cavity and induce mode hybridization, leading to excellent optimization of both sensitivity and full width at half maximum compared with normal single layer Au nanohole sensors. When modified with CD63 or EpCAM aptamers, a detection of limit (LOD) of as low as 600 particles/µL was achieved. The sensors showed good capability to distinguish between non-tumor derived L02 exosomes and tumor derived HepG2 exosomes. Additionally, high reproducibility was also achieved in detection of artificial serum samples with RSD as low as 2%, making it feasible for clinical applications. This mode hybridization plasmonic sensor provides an effective approach to optimize the detection sensitivity of exosomes, pushing SPR sensing one step further towards cancer diagnosis.

Characterization of the structural and molecular interactions of Ferulic acid ethyl ester with human serum albumin and Lysozyme through multi-methods.

Ferulic acid ethyl ester (FAEE) is an essential raw material for the formulation of drugs for cardiovascular and cerebrovascular diseases and leukopenia. It is also used as a fixed aroma agent for food production due to its high pharmacological activity. In this study, the interaction of FAEE with Human serum albumin (HSA) and Lysozyme (LZM) was characterized by multi-spectrum and molecular dynamics simulations at four different temperatures. Additionally, the quenching mechanism of FAEE-HSA and FAEE-LZM were explored. Meanwhile, the binding constants, binding sites, thermodynamic parameters, molecular dynamics, molecular docking binding energy, and the influence of metal ions in the system were evaluated. The results of Synchronous fluorescence spectroscopy, UV-vis spectroscopy, CD, three-dimensional fluorescence spectrum, and resonance light scattering showed that the microenvironment of HSA and LZM and the protein conformation changed in the presence of FAEE. Furthermore, the effects of some common metal ions on the binding constants of FAEE-HSA and FAEE-LZM were investigated. Overall, the experimental results provide a theoretical basis for promoting the application of FAEE in the cosmetics, food, and pharmaceutical industries and significant guidance for food safety, drug design, and development.

Surface-Enhanced Raman Spectroscopy: Current Understanding, Challenges, and Opportunities.

While surface-enhanced Raman spectroscopy (SERS) has experienced substantial advancements since its discovery in the 1970s, it is an opportunity to celebrate achievements, consider ongoing endeavors, and anticipate the future trajectory of SERS. In this perspective, we encapsulate the latest breakthroughs in comprehending the electromagnetic enhancement mechanisms of SERS, and revisit CT mechanisms of semiconductors. We then summarize the strategies to improve sensitivity, selectivity, and reliability. After addressing experimental advancements, we comprehensively survey the progress on spectrum-structure correlation of SERS showcasing their important role in promoting SERS development. Finally, we anticipate forthcoming directions and opportunities, especially in deepening our insights into chemical or biological processes and establishing a clear spectrum-structure correlation.

The microbial metabolite agmatine acts as an FXR agonist to promote polycystic ovary syndrome in female mice.

Polycystic ovary syndrome (PCOS), an endocrine disorder afflicting 6-20% of women of reproductive age globally, has been linked to alterations in the gut microbiome. We previously showed that in PCOS, elevation of Bacteroides vulgatus in the gut microbiome was associated with altered bile acid metabolism. Here we show that B. vulgatus also induces a PCOS-like phenotype in female mice via an alternate mechanism independent of bile acids. We find that B. vulgatus contributes to PCOS-like symptoms through its metabolite agmatine, which is derived from arginine by arginine decarboxylase. Mechanistically, agmatine activates the farnesoid X receptor (FXR) pathway to subsequently inhibit glucagon-like peptide-1 (GLP-1) secretion by L cells, which leads to insulin resistance and ovarian dysfunction. Critically, the GLP-1 receptor agonist liraglutide and the arginine decarboxylase inhibitor difluoromethylarginine ameliorate ovarian dysfunction in a PCOS-like mouse model. These findings reveal that agmatine-FXR-GLP-1 signalling contributes to ovarian dysfunction, presenting a potential therapeutic target for PCOS management.

Pathologic TDP-43 downregulates myelin gene expression in the monkey brain.

Growing evidence indicates that non-neuronal oligodendrocyte plays an important role in Amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. In patient's brain, the impaired myelin structure is a pathological feature with the observation of TDP-43 in cytoplasm of oligodendrocyte. However, the mechanism underlying the gain of function by TDP-43 in oligodendrocytes, which are vital for the axonal integrity, remains unclear. Recently, we found that the primate-specific cleavage of truncated TDP-43 fragments occurred in cytoplasm of monkey neural cells. This finding opened up the avenue to investigate the myelin integrity affected by pathogenic TDP-43 in oligodendrocytes. In current study, we demonstrated that the truncated TDP-35 in oligodendrocytes specifically, could lead to the dysfunctional demyelination in corpus callosum of monkey. As a consequence of the interaction of myelin regulatory factor with the accumulated TDP-35 in cytoplasm, the downstream myelin-associated genes expression was downregulated at the transcriptional level. Our study aims to investigate the potential effect on myelin structure injury, affected by the truncated TDP-43 in oligodendrocyte, which provided the additional clues on the gain of function during the progressive pathogenesis and symptoms in TDP-43 related diseases.

Electroacupuncture improves apoptosis of nucleus pulposus cells via the IL-22/JAK2-STAT3 signaling pathway in a rat model of cervical intervertebral disk degeneration.

BACKGROUND: Cervical spondylosis (CS) is a prevalent disorder that can have a major negative impact on quality of life. Traditional conservative treatment has limited efficacy, and electroacupuncture (EA) is a novel treatment option. We investigated the application and molecular mechanism of EA treatment in a rat model of cervical intervertebral disk degeneration (CIDD). METHODS: The CIDD rat model was established, following which rats in the electroacupuncture (EA) group received EA. For overexpression of IL-22 or inhibition of JAK2-STAT3 signaling, the rats were injected intraperitoneally with recombinant IL-22 protein (p-IL-22) or the JAK2-STAT3 (Janus kinase 2-signal transducer and activator of transcription protein 3) inhibitor AG490 after model establishment. Rat nucleus pulposus (NP) cells were isolated and cultured. Cell counting kit-8 and flow cytometry were used to analyze the viability and apoptosis of the NP cells. Expression of IL-22, JAK2 and STAT3 was determined using RT-qPCR. Expression of IL-22/JAK2-STAT3 pathway and apoptosis related proteins was detected by Western blotting (WB). RESULTS: EA protected the NP tissues of CIDD rats by regulating the IL-22/JAK2-STAT3 pathway. Overexpression of IL-22 significantly promoted the expression of tumor necrosis factor (TNF)-α, IL-6, IL-1ß, matrix metalloproteinase (MMP)3 and MMP13 compared with the EA group. WB demonstrated that the expression of IL-22, p-JAK2, p-STAT3, caspase-3 and Bax in NP cells of the EA group was significantly reduced and Bcl-2 elevated compared with the model group. EA regulated cytokines and MMP through activation of IL-22/JAK2-STAT3 signaling in CIDD rat NP cells. CONCLUSION: We demonstrated that EA affected apoptosis by regulating the IL-22/JAK2-STAT3 pathway in NP cells and reducing inflammatory factors in the CIDD rat model. The results extend our knowledge of the mechanisms of action underlying the effects of EA as a potential treatment approach for CS in clinical practice.

Metabolic Dysfunction-Associated Steatohepatitis Detected by Neutrophilic Crown-Like Structures in Morbidly Obese Patients: A Multicenter and Clinicopathological Study.

Metabolic dysfunction-associated steatohepatitis (MASH) is the progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD), and closely associated with a high risk of liver-related morbidity and mortality. Although enhanced neutrophil infiltration of the liver is a histological hallmark of MASH, the morphological pattern of hepatic neutrophils and their relevance to the definition of MASH remain unknown. This clinicopathological study aimed to determine the association of neutrophilic crown-like structures (CLSs) in liver biopsies and evaluate their relevance to the histological diagnosis of MASH. A total of 483 morbidly obese adults who underwent bariatric surgery were recruited. Neutrophilic CLSs in liver biopsies were detected by immunohistochemistry for neutrophil elastase and proteinase 3. All participants were classified into 4 histological subgroups: no MASLD (118, 24.4%), MASLD (76, 15.7%), borderline MASH (185, 38.3%), and definite MASH (104, 21.5%). In the discovery cohort (n = 379), the frequency of neutrophilic CLSs increased in line with the severity of liver disease. The number of neutrophilic CLSs was positively correlated with established histological characteristics of MASH. At a cutoff value of <0.3 per 20× microscopic field, the number of neutrophilic CLSs yielded a robust diagnostic accuracy to discriminate no MASLD and MASLD from borderline MASH and definite MASH; a cutoff at >1.3 per 20× microscopic field exhibited a statistically significant accuracy to distinguish definite MASH from other groups (no MASLD, MASLD, and borderline MASH). The significance of neutrophilic CLSs in identifying borderline MASH and definite MASH was confirmed in an external validation cohort (n = 104). The frequency of neutrophilic CLSs was significantly higher than that of macrophagic CLSs. In conclusion, neutrophilic CLSs in the liver represent a typical histological characteristic of MASH and may serve as a promising indicator to improve the diagnostic accuracy of MASH during histological assessment of liver biopsies.

Candida albicans accelerates atherosclerosis by activating intestinal hypoxia-inducible factor2α signaling.

The gut microbiota is closely linked to atherosclerosis. However, the role of intestinal fungi, essential members of the complex microbial community, in atherosclerosis is poorly understood. Herein, we show that gut fungi dysbiosis is implicated in patients with dyslipidemia, characterized by higher levels of Candida albicans (C. albicans), which are positively correlated with plasma total cholesterol and low-density lipoprotein-cholesterol (LDL-C) levels. Furthermore, C. albicans colonization aggravates atherosclerosis progression in a mouse model of the disease. Through gain- and loss-of-function studies, we show that an intestinal hypoxia-inducible factor 2α (HIF-2α)-ceramide pathway mediates the effect of C. albicans. Mechanistically, formyl-methionine, a metabolite of C. albicans, activates intestinal HIF-2α signaling, which drives increased ceramide synthesis to accelerate atherosclerosis. Administration of the HIF-2α selective antagonist PT2385 alleviates atherosclerosis in mice by reducing ceramide levels. Our findings identify a role for intestinal fungi in atherosclerosis progression and highlight the intestinal HIF-2α-ceramide pathway as a target for atherosclerosis treatment.

The Hydrophilic Metabolite UMP Alleviates Obesity Traits through a HIF2α-ACER2-Ceramide Signaling Axis.

Metabolic abnormalities contribute to the pathogenesis of obesity and its complications. Yet, the understanding of the interactions between critical metabolic pathways that underlie obesity remains to be improved, in part owing to the lack of comprehensive metabolomics studies that reconcile data from both hydrophilic and lipophilic metabolome analyses that can lead to the identification and characterization of key signaling networks. Here, the study conducts a comprehensive metabolomics analysis, surveying lipids and hydrophilic metabolites of the plasma and omental adipose tissue of obese individuals and the plasma and epididymal adipose tissue of mice. Through these approaches, it is found that a significant accumulation of ceramide due to inhibited sphingolipid catabolism, while a significant reduction in the levels of uridine monophosphate (UMP), is critical to pyrimidine biosynthesis. Further, it is found that UMP administration restores sphingolipid homeostasis and can reduce obesity in mice by reversing obesity-induced inhibition of adipocyte hypoxia inducible factor 2a (Hif2α) and its target gene alkaline ceramidase 2 (Acer2), so as to promote ceramide catabolism and alleviate its accumulation within cells. Using adipose tissue Hif2α-specific knockout mice, the study further demonstrates that the presence of UMP can alleviate obesity through a HIF2α-ACER2-ceramide pathway, which can be a new signaling axis for obesity improvement.

STING deficiency alleviates ferroptosis through FPN1 stabilization in diabetic kidney disease.

Ferroptosis, a form of cell death driven by iron-dependent lipid peroxidation, has known as one of the most significant pathological processes involved in diabetic kidney disease (DKD). Stimulator of interferon genes (STING) has been demonstrated its potential in regulating ferroptosis, but the regulatory role in DKD mice and underlying mechanisms haven't been illustrated. To elucidate whether and how STING regulates ferroptosis in DKD, we detected the influence of STING on diabetic-related ferroptosis in a diabetic model and in erastin-induced renal tubular epithelial cells (RTECs). Our study demonstrated that STING was abnormally activated and promoted ferroptosis in DKD. STING deficiency alleviated renal pathologic damages and disfunction in diabetic mice via alleviating ferroptosis and reducing oxidative stress. Mechanismly, STING inhibition was shown to improve ferroptosis and reduce oxidative stress in erastin-induced RTECs. The disruption of ferroportin1 (FPN1) on the basis of STING inhibition abolished the improvements in ferroptosis and promoted reactive oxygen species (ROS) generation. Further, STING inhibition alleviated ferroptosis via stabilizing FPN1 protein level by decreasing ubiquitinated FPN1 for proteasomal degradation. In conclusion, STING deficiency protected against diabetic renal injury via alleviating ferroptosis through stabilizing FPN1 and reducing oxidative stress, providing a possible potential approach for the treatment of DKD.

Large animal models for Huntington's disease research.

Huntington's disease (HD) is a hereditary neurodegenerative disorder for which there is currently no effective treatment available. Consequently, the development of appropriate disease models is critical to thoroughly investigate disease progression. The genetic basis of HD involves the abnormal expansion of CAG repeats in the huntingtin ( HTT) gene, leading to the expansion of a polyglutamine repeat in the HTT protein. Mutant HTT carrying the expanded polyglutamine repeat undergoes misfolding and forms aggregates in the brain, which precipitate selective neuronal loss in specific brain regions. Animal models play an important role in elucidating the pathogenesis of neurodegenerative disorders such as HD and in identifying potential therapeutic targets. Due to the marked species differences between rodents and larger animals, substantial efforts have been directed toward establishing large animal models for HD research. These models are pivotal for advancing the discovery of novel therapeutic targets, enhancing effective drug delivery methods, and improving treatment outcomes. We have explored the advantages of utilizing large animal models, particularly pigs, in previous reviews. Since then, however, significant progress has been made in developing more sophisticated animal models that faithfully replicate the typical pathology of HD. In the current review, we provide a comprehensive overview of large animal models of HD, incorporating recent findings regarding the establishment of HD knock-in (KI) pigs and their genetic therapy. We also explore the utilization of large animal models in HD research, with a focus on sheep, non-human primates (NHPs), and pigs. Our objective is to provide valuable insights into the application of these large animal models for the investigation and treatment of neurodegenerative disorders.

Multi-omics and gut microbiome: Unveiling the pathogenic mechanisms of early-life pesticide exposure.

The extensive application of pesticides in agricultural production has raised significant concerns about its impact on human health. Different pesticides, including fungicides, insecticides, and herbicides, cause environmental pollution and health problems for non-target organisms. Infants and young children are so vulnerable to the harmful effects of pesticide exposure that early-life exposure to pesticides deserves focused attention. Recent research lays emphasis on understanding the mechanism between negative health impacts and early-life exposure to various pesticides. Studies have explored the impacts of exposure to these pesticides on model organisms (zebrafish, rats, and mice), as well as the mechanism of negative health effects, based on advanced methodologies like gut microbiota and multi-omics. These methodologies help comprehend the pathogenic mechanisms associated with early-life pesticide exposure. In addition to presenting health problems stemming from early-life exposure to pesticides and their pathogenic mechanisms, this review proposes expectations for future research. These proposals include focusing on identifying biomarkers that indicate early-life pesticide exposure, investigating transgenerational effects, and seeking effective treatments for diseases arising from such exposure. This review emphasizes how to understand the pathogenic mechanisms of early-life pesticide exposure through gut microbiota and multi-omics, as well as the adverse health effects of such exposure.

Metamaterial Inspired Varactor-Tuned Antenna with Frequency Reconfigurability and Pattern Diversity.

A metamaterial-inspired varactor-tuned antenna with frequency reconfigurability and pattern diversity is designed. Two different versions of a reconfigurable structure are integrated into a single antenna to excite two different orthogonal patterns, which realizes pattern diversity for MIMO applications. The outer annular Composite Right-/Left-Handed Transmission Line (CRLH-TL) works at the 1 mode and provides a broadside pattern, and the inner circular radiator loaded with split ring resonators (SRR) operates at the 0 mode and radiates an omnidirectional pattern, which realizes pattern diversity. By using surface-mounted varactors, the operating frequencies for the two radiation patterns can be tuned over a wide frequency range, from 1.7 GHz to 2.2 GHz, covering the 1.71-2.17 GHz LTE band, and a low mutual coupling between the two radiators is achieved. The antenna has also been prototyped. The measured results are in good agreement with the simulation results, verifying the proposed concept. The dual-mode MIMO system equipped with the proposed antenna elements is discussed within the context of a 3-D channel model, and it shows a superior array compactness and spectral efficiency (SE) performance compared to scenarios with single-mode elements.