Investigating long-term changes in surface water temperature of Dongting Lake using Landsat imagery, China.

Lake surface water temperature (LSWT) plays a crucial role in assessing the health of aquatic ecosystems. Variations in LSWT can significantly impact the physical, chemical, and biological processes within lakes. This study investigates the long-term changes in surface water temperature of the Dongting Lake, China. The LSWT is retrieved using Landsat thermal infrared imageries from 1988 to 2022 and validated with in situ observations, and the change characteristics of LSWT and near-surface air temperature (NSAT) as well as the spatial distribution characteristics of LSWT are analyzed. Additionally, the contribution rates of different meteorological factors to LSWT are quantified. The results show that the accuracy assessment of satellite-derived temperatures indicates a Nash-Sutcliffe efficiency coefficient (NSE) of 0.961, suggesting an accurate retrieval of water temperature. From 1988 to 2022, both the annual average LSWT and NSAT of Dongting Lake exhibit an increasing trend, with similar rates of warming. They both undergo a mutation in 1997 and have the main periods on the 11-year and 4-year time scales. The changes in NSAT emerge as one of the important factors contributing to variations in LSWT. Among the multiple meteorological factors, NSAT exhibits a significant correlation with LSWT (R = 0.822, α < 0.01). Furthermore, NSAT accounts for the highest contribution rate to LSWT, amounting to 67.5%. The distribution of LSWT within Dongting Lake exhibits spatial variations, with higher LSWT observed on the west part compared to the east part during summer, while lower LSWT occurs on the west part during winter. The findings of this study can provide a scientific understanding for the long-term thermal regimes of lakes and help advance sustainable lake management.

Crosstalk Between the Nervous System and Colorectal Cancer.

The nervous system is the dominant regulatory system in the human body. The traditional theory is that tumors lack innervation. However, an increasing number of studies have shown complex bidirectional interactions between tumors and the nervous system. Globally, colorectal cancer (CRC) is the third most common cancer. With the rise of tumor neuroscience, the role of nervous system imbalances in the occurrence and development of CRC has attracted increasing amounts of attention. However, there are still many gaps in the research on the interactions and mechanisms involved in the nervous system in CRC. This article systematically reviews emerging research on the bidirectional relationships between the nervous system and CRC, focusing on the following areas: (1) Effects of the nervous system on colon cancer. (2) Effects of CRC on the nervous system. (3) Treatment of CRC associated with the nervous system.

Extreme drought along the tropic of cancer (Yunnan section) and its impact on vegetation.

The frequent occurrence of extreme weather events is one of the future prospects of climate change, and how ecosystems respond to extreme drought is crucial for response to climate change. Taking the extreme drought event in the Tropic of Cancer (Yunnan section) during 2009-2010 as a case study, used the standardized precipitation evapotranspiration index to analyse the impact of extreme drought on enhanced vegetation index (EVI), leaf area index (LAI) and gross primary productivity (GPP), and to analyzed the post extreme drought vegetation recovery status. The results indicate the following: (1) Due to the cumulative effects of drought and vegetation phenology, vegetation growth in the months of March to May in 2010 was more severely affected. (2) Compared to EVI and LAI, GPP is more sensitive to drought and can accurately indicate areas where drought has impacted vegetation. (3) Following an extreme drought event, 70% of the vegetation can recover within 3 months, while 2.87-6.57% of the vegetation will remain unrecovered after 6 months. (4) Cropland and grassland show the strongest response, with longer recovery times, while woodland and shrubland exhibit weaker responses and shorter recovery times. This study provides a reference for the effects of extreme drought on vegetation.

Effects of non-landslide sampling strategies on machine learning models in landslide susceptibility mapping.

This study aims to explore the effects of different non-landslide sampling strategies on machine learning models in landslide susceptibility mapping. Non-landslide samples are inherently uncertain, and the selection of non-landslide samples may suffer from issues such as noisy or insufficient regional representations, which can affect the accuracy of the results. In this study, a positive-unlabeled (PU) bagging semi-supervised learning method was introduced for non-landslide sample selection. In addition, buffer control sampling (BCS) and K-means (KM) clustering were applied for comparative analysis. Based on landslide data from Qiaojia County, Yunnan Province, China, collected in 2014, three machine learning models, namely, random forest, support vector machine, and CatBoost, were used for landslide susceptibility mapping. The results show that the quality of samples selected using different non-landslide sampling strategies varies significantly. Overall, the quality of non-landslide samples selected using the PU bagging method is superior, and this method performs best when combined with CatBoost for predicting (AUC = 0.897) landslides in very high and high susceptibility zones (82.14%). Additionally, the KM results indicated overfitting, displaying high accuracy for validation but poor statistical outcomes for zoning. The BCS results were the worst.

Targeted Delivery of Peptide Nucleic Acid by Biomimetic Nanoparticles Based on Extracellular Vesicle-coated Mesoporous Silica Nanoparticles.

BACKGROUND: Peptide nucleic acid (PNA) plays an important role in antimicrobial activity, but its cellular permeability is poor. To overcome this limitation, we constructed biomimetic nanoparticles by using extracellular vesicle (EV)-coated mesoporous silicon nanoparticles (MSNs) to deliver PNA to Staphylococcus aureus (S. aureus) and improve its antisense therapeutic effect. METHOD: MSN was prepared by the sol-gel method, and EV was extracted by affinity resin chromatography. EV was coated on MSN by simple sonication (50 W, 3 min) to prepare biomimetic nanoparticles with PNA-loaded MSN as the core and EV isolated from S. aureus as the shell. RESULTS: The MSN prepared by the sol-gel method had a uniform particle size (100 nm) and well-defined pore size for loading PNA with good encapsulation efficiency (62.92%) and drug loading (7.74%). The concentration of EV extracted by affinity resin chromatography was about 1.74 mg/mL. EV could be well coated on MSN through simple ultrasonic treatment (50 W, 3 min), and the stability and blood compatibility of MSN@ EV were good. Internalization experiments showed that EV could selectively enhance the uptake of biomimetic nanoparticles by S. aureus. Preliminary in vitro antibacterial tests revealed that PNA@MSN@EV exhibited enhanced antibacterial activity against S. aureus and had stronger bactericidal activity than free PNA and PNA@MSN at equivalent PNA concentrations (8 µM). CONCLUSION: Biomimetic nanoparticles based on EV-coated MSN offer a new strategy to improve the efficacy of PNA for the treatment of bacterial infections, and the technology holds promise for extension to the delivery of antibiotics that are traditionally minimally effective or prone to resistance.

The Traf2 and NcK interacting kinase inhibitor NCB-0846 suppresses seizure activity involving the decrease of GRIA1.

Epilepsy, one of the most common neurological disorders, is characterized by spontaneous recurrent seizures. Temporal lobe epilepsy (TLE) is one of the most common medically intractable seizure disorders. Traf2-and NcK-interacting kinase (TNIK) has recently attracted attention as a critical modulation target of many neurological and psychiatric disorders, but its role in epilepsy remains unclear. In this study, we hypothesized the involvement of TNIK in epilepsy and investigated TNIK expression in patients with intractable TLE and in a pilocarpine-induced rat model of epilepsy by western blotting, immunofluorescence, and immunohistochemistry. A pentylenetetrazole (PTZ)-induced epilepsy rat model was used to determine the effect of the TNIK inhibitor NCB-0846 on behavioral manifestations of epilepsy. Coimmunoprecipitation (Co-IP)/mass spectrometry (MS) was used to identify the potential mechanism. Through Co-IP, we detected and confirmed the main potential TNIK interactors. Subcellular fractionation was used to establish the effect of NCB-0846 on the expression of the main interactors in postsynaptic density (PSD) fractions. We found that TNIK was primarily located in neurons and decreased significantly in epilepsy model rats and TLE patients compared with controls. NCB-0846 delayed kindling progression and decreased seizure severity. Co-IP/MS identified 63 candidate TNIK interactors in rat hippocampi, notably CaMKII. Co-IP showed that TNIK might correlate with endogenous GRIA1, SYN2, PSD-95, CaMKIV, GABRG1, and GABRG2. In addition, the significant decrease in GRIA1 in hippocampal total lysate and PSDs after NCB-0846 treatment might help modify the progression of PTZ kindling. Our results suggest that TNIK contributes to epileptic pathology and is a potential antiepileptic drug target.

Study on landslide susceptibility mapping with different factor screening methods and random forest models.

The number of input factors affects the prediction accuracy of a model. Factor screening plays an important role as the starting point for data input. The aim of this study is to explore the influence of different factor screening methods on the prediction results. Taking the 2014 landslide inventory of Jingdong County as an example, a landslide database was constructed based on 136 landslide events and 11 selected factors, which were randomly divided into a training dataset and a test dataset according to a ratio of 7:3. Four factor screening methods, namely, the information gain ratio (IGR), GeoDetector, Pearson correlation coefficient and multicollinearity test (MT), were selected to screen the factors. A random forest (RF) model was then used in combination with each factor set for landslide susceptibility mapping (LSM). Finally, accuracy validation was performed using confusion matrices and ROC curves. The results show that factor screening is beneficial in improving the accuracy of the resulting model compared to the original model. Second, the IGR_RF model had the highest AUC value (0.9334), which was higher than that of the MT_RF model without factor screening (0.9194), and the IGR_RF model predicted the most landslides in the very high susceptibility zone (51.22%), indicating the good prediction performance of the IGR_RF model. Finally, the factor weighting analysis revealed that NDVI, elevation and aspect had the greatest influence on landslides in Jingdong County and that curvature had the least influence on landslides. This study can provide a reference for factor screening in LSM.

Three-Dimensional Electrochemical Sensors for Food Safety Applications.

Considering the increasing concern for food safety, electrochemical methods for detecting specific ingredients in the food are currently the most efficient method due to their low cost, fast response signal, high sensitivity, and ease of use. The detection efficiency of electrochemical sensors is determined by the electrode materials' electrochemical characteristics. Among them, three-dimensional (3D) electrodes have unique advantages in electronic transfer, adsorption capacity and exposure of active sites for energy storage, novel materials, and electrochemical sensing. Therefore, this review begins by outlining the benefits and drawbacks of 3D electrodes compared to other materials before going into more detail about how 3D materials are synthesized. Next, different types of 3D electrodes are outlined together with common modification techniques for enhancing electrochemical performance. After this, a demonstration of 3D electrochemical sensors for food safety applications, such as detecting components, additives, emerging pollutants, and bacteria in food, was given. Finally, improvement measures and development directions of electrodes with 3D electrochemical sensors are discussed. We think that this review will help with the creation of new 3D electrodes and offer fresh perspectives on how to achieve extremely sensitive electrochemical detection in the area of food safety.

Advances in Portable Heavy Metal Ion Sensors.

Heavy metal ions, one of the major pollutants in the environment, exhibit non-degradable and bio-chain accumulation characteristics, seriously damage the environment, and threaten human health. Traditional heavy metal ion detection methods often require complex and expensive instruments, professional operation, tedious sample preparation, high requirements for laboratory conditions, and operator professionalism, and they cannot be widely used in the field for real-time and rapid detection. Therefore, developing portable, highly sensitive, selective, and economical sensors is necessary for the detection of toxic metal ions in the field. This paper presents portable sensing based on optical and electrochemical methods for the in situ detection of trace heavy metal ions. Progress in research on portable sensor devices based on fluorescence, colorimetric, portable surface Raman enhancement, plasmon resonance, and various electrical parameter analysis principles is highlighted, and the characteristics of the detection limits, linear detection ranges, and stability of the various sensing methods are analyzed. Accordingly, this review provides a reference for the design of portable heavy metal ion sensing.

DPP-Cu2+ Complexes Gated Mesoporous Silica Nanoparticles For pH and Redox Dual Stimuli-Responsive Drug Delivery.

OBJECTIVE: A simple pH and redox dual stimuli-responsive diketopyrrolopyrrole (DPP)-Cu2+ complexes gated mesoporous silica nanoparticles (MSN) were prepared for precise drug delivery and controlled drug release. METHOD: MSN was prepared by sol-gel method and then laminated. Carboxylic acid (CA)-Pyrrolo[3,4-c] pyrrole-1,4-dione, 2,5-dihydro-3,6-di-2-pyridinyl (PyDPP) was grafted onto the surface of amino-functionalized MSN (MSN-NH2) through a simple amide reaction and then complexed with Cu2+ to form gated molecules after doxorubicin (DOX) loading. RESULTS: Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Low-angle X-ray diffraction (XRD) showed that MSN with uniform particle size (100 nm) and porous structure was successfully prepared. The prepared MSN, MSN- NH2, and MSN-DPP were fully characterized by Zeta potential, Fourier transforms infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and nitrogen adsorption- desorption. High DOX-loading capacity (18.22%) and encapsulation efficiency (89.16%) were achieved by optimizing the mass ratio of MSN to DOX. Release studies showed that the gated molecules of our designed DPP-Cu2+ complexes had a good blocking effect under physiological conditions (the cumulative release rate of drugs within 24 hours was only 4.18%) and responded well to the pH and redox glutathione (GSH) dual stimuli. In vitro cytotoxicity assay showed that MSN-DPP-Cu2+ had good biocompatibility in both Hep G2 cells and L02 cells (the relative cell viability of both cells within 48 hours was above 97%), and the MSN-DPP-Cu2+@DOX could be triggered for efficient drug release in Hep G2 cells. CONCLUSION: The MSN-DPP-Cu2+ described in this research may be a good delivery system for the controlled release of antitumor drugs and can provide a potential possibility for clinical application in the future.

Higher intraoperative mean arterial blood pressure does not reduce postoperative delirium in elderly patients following gastrointestinal surgery: A prospective randomized controlled trial.

BACKGROUND: This study aimed to describe the relationship between the different levels of intraoperative mean arterial blood pressure (MAP) and postoperative delirium in elderly patients undergoing gastrointestinal laparoscopic surgery. MATERIALS AND METHODS: This prospective controlled clinical trial enrolled 116 patients aged 65 to 85 years who underwent gastrointestinal laparoscopic surgery. These patients were randomized 1:1 to a MAP goal of 65 to 85 mmHg (L group) or an 86 to 100 mmHg (H group). The primary endpoint was the incidence of postoperative delirium, assessed twice daily with the Confusion Assessment Method (CAM) and Richmond Agitation-Sedation Scale (RASS) during the first five postoperative days. Delirium severity was evaluated with the Delirium-O-Meter (D-O-M). RESULTS: 108 patients (L group n = 55, H group n = 53) were eventually included in intention-to-treat analyses. Postoperative delirium occurred in 18 (32.7%) of 55 cases of L group and in 15 (28.3%) of 53 cases of H group. The incidence of delirium subtypes between the two groups: hypoactive delirium 14.5% (8/55) vs 11.3% (6/53); hyperactive delirium 7.3% (4/55) vs 3.8% (2/53); mixed delirium 10.9% (6/55) vs 13.2% (7/53). However, the L group showed higher D-O-M scores of the first episode of delirium: 14.5 (Q1 = 12, Q3 = 18.5) vs 12 (Q1 = 10, Q3 = 14), which means the delirium is more severe. CONCLUSIONS: Compared with 65 to 85 mmHg, maintaining intraoperative MAP at 86-100 mmHg did not reduce the incidence of postoperative delirium in elderly patients undergoing gastrointestinal laparoscopic surgery. However, the severity of delirium could be reduced and blood loss is a risk factor for postoperative delirium.

Loss of function of CMPK2 causes mitochondria deficiency and brain calcification.

Brain calcification is a critical aging-associated pathology and can cause multifaceted neurological symptoms. Cerebral phosphate homeostasis dysregulation, blood-brain barrier defects, and immune dysregulation have been implicated as major pathological processes in familial brain calcification (FBC). Here, we analyzed two brain calcification families and identified calcification co-segregated biallelic variants in the CMPK2 gene that disrupt mitochondrial functions. Transcriptome analysis of peripheral blood mononuclear cells (PBMCs) isolated from these patients showed impaired mitochondria-associated metabolism pathways. In situ hybridization and single-cell RNA sequencing revealed robust Cmpk2 expression in neurons and vascular endothelial cells (vECs), two cell types with high energy expenditure in the brain. The neurons in Cmpk2-knockout (KO) mice have fewer mitochondrial DNA copies, down-regulated mitochondrial proteins, reduced ATP production, and elevated intracellular inorganic phosphate (Pi) level, recapitulating the mitochondrial dysfunction observed in the PBMCs isolated from the FBC patients. Morphologically, the cristae architecture of the Cmpk2-KO murine neurons was also impaired. Notably, calcification developed in a progressive manner in the homozygous Cmpk2-KO mice thalamus region as well as in the Cmpk2-knock-in mice bearing the patient mutation, thus phenocopying the calcification pathology observed in the patients. Together, our study identifies biallelic variants of CMPK2 as novel genetic factors for FBC; and demonstrates how CMPK2 deficiency alters mitochondrial structures and functions, thereby highlighting the mitochondria dysregulation as a critical pathogenic mechanism underlying brain calcification.

Multiple amplification-based fluorometric aptasensor for highly sensitive detection of Staphylococcus aureus.

Rapid and accurate detection and identification of Staphylococcus aureus (S. aureus) are of great significance for food safety, environmental monitoring, early clinical diagnosis, and prevention of the spread of drug-resistant bacteria. Herein, we design a fluorometric aptasensor for ultra-sensitive, specific, and rapid detection of S. aureus. The apasensor combines the enrichment and separation of magnetic nanoparticles (MNPs), the biotin-streptavidin conjugation system, and a single S. aureus can release four signaling probes for signal amplification. Aptamer acts as a specific biorecognition element of S. aureus. Four FAM-labeled partially complementary sequences (FAM-pcDNAs) were used as signaling probes. The aptamers were sequential hybridized with the four FAM-pcDNAs to form aptamer&pcDNAs, which were then bound to MNPs via the biotin-streptavidin. When the aptamer specifically recognizes and binds to S. aureus, the FAM-pcDNAs signaling probes are replaced and released into the supernatant. The concentration of S. aureus can be quantified by measuring the fluorescence intensity (λexc/em = 492/520 nm) of the replaced signaling probe FAM-pcDNAs. The results show that the proposed fluorometric aptasensor displays good specificity, ultra-high sensitivity (1.23 cfu/mL), wide linear range (1 ~ 108 cfu/mL), and fast detection speed (~ 1.5 h). The recovery test verifies further that the proposed fluorometric aptasensor can detect S. aureus in spiked blood samples. Since aptamers are easy to customize, we believe that fluorometric aptasensors based on multiple amplification have broad prospects in the construction of practical high-performance biosensors for bacterial detection. KEY POINTS: • Multiple amplification-based fluorometric aptasensor for S. aureus is developed • The aptasensor displays high specificity with a LOD of 1.23 CFU/mL • The aptasensor can directly detect S. aureus in spiked blood samples.

Recent Advances in Aptasensors For Rapid and Sensitive Detection of Staphylococcus Aureus.

The infection of Staphylococcus aureus (S.aureus) and the spread of drug-resistant bacteria pose a serious threat to global public health. Therefore, timely, rapid and accurate detection of S. aureus is of great significance for food safety, environmental monitoring, clinical diagnosis and treatment, and prevention of drug-resistant bacteria dissemination. Traditional S. aureus detection methods such as culture identification, ELISA, PCR, MALDI-TOF-MS and sequencing, etc., have good sensitivity and specificity, but they are complex to operate, requiring professionals and expensive and complex machines. Therefore, it is still challenging to develop a fast, simple, low-cost, specific and sensitive S. aureus detection method. Recent studies have demonstrated that fast, specific, low-cost, low sample volume, automated, and portable aptasensors have been widely used for S. aureus detection and have been proposed as the most attractive alternatives to their traditional detection methods. In this review, recent advances of aptasensors based on different transducer (optical and electrochemical) for S. aureus detection have been discussed in details. Furthermore, the applications of aptasensors in point-of-care testing (POCT) have also been discussed. More and more aptasensors are combined with nanomaterials as efficient transducers and amplifiers, which appears to be the development trend in aptasensors. Finally, some significant challenges for the development and application of aptasensors are outlined.

SAPAP3 regulates epileptic seizures involving GluN2A in post-synaptic densities.

Aberrantly synchronized neuronal discharges in the brain lead to epilepsy, a devastating neurological disease whose pathogenesis and mechanism are unclear. SAPAP3, a cytoskeletal protein expressed at high levels in the postsynaptic density (PSD) of excitatory synapses, has been well studied in the striatum, but the role of SAPAP3 in epilepsy remains elusive. In this study, we sought to investigate the molecular, cellular, electrophysiological and behavioral consequences of SAPAP3 perturbations in the mouse hippocampus. We identified a significant increase in the SAPAP3 levels in patients with temporal lobe epilepsy (TLE) and in mouse models of epilepsy. In addition, behavioral studies showed that the downregulation of SAPAP3 by shRNA decreased the seizure severity and that the overexpression of SAPAP3 by recombinant SAPAP3 yielded the opposite effect. Moreover, SAPAP3 affected action potentials (APs), miniature excitatory postsynaptic currents (mEPSCs) and N-methyl-D-aspartate receptor (NMDAR)-mediated currents in the CA1 region, which indicated that SAPAP3 plays an important role in excitatory synaptic transmission. Additionally, the levels of the GluN2A protein, which is involved in synaptic function, were perturbed in the hippocampal PSD, and this perturbation was accompanied by ultrastructural morphological changes. These results revealed a previously unknown function of SAPAP3 in epileptogenesis and showed that SAPAP3 may represent a novel target for the treatment of epilepsy.

The novel HLA-A*31:191 allele was identified in a Chinese platelet donor.

HLA-A*31:191 differs from HLA-A*31:01:02:01 by one single nucleotide substitution at nucleotide 74.

Application strategies of peptide nucleic acids toward electrochemical nucleic acid sensors.

Peptide nucleic acids (PNAs) have attracted tremendous interest in the fabrication of highly sensitive electrochemical nucleic acid biosensors due to their higher stability and increased sensitivity than common DNA probes. The neutral pseudopeptide backbone of PNAs not only makes the PNA/DNA duplexes more stable but also provides many opportunities to construct ultrasensitive nucleic acid sensors. This review presents the details of various protocols for the construction of PNA-based electrochemical nucleic acid sensors. The crucial factors, origin, and development of PNA, immobilization methods of PNA probes and signal generation mechanisms, are discussed. This review aims to provide a reference for ultrasensitive PNA electrochemical biosensor preparation.

Safety and efficacy of remimazolam compared with propofol in induction of general anesthesia.

BACKGROUND: Remimazolam is a new ultrashort acting benzodiazepine anesthetic which has predictable sedative duration and rapid recovery in gastrointestinal endoscopy. Propofol is a commonly used intravenous anesthetic in clinical work which also has rapid action, short action time and rapid recovery. To date, there have been relatively few articles comparing the two for general anesthesia induction. So, we conducted a randomized trial to evaluate whether remimazolam is superior to propofol during anesthesia induction in terms of efficacy and safety. METHODS: One hundred and eighty nine ASA I or II patients scheduled for elective surgery were divided into four groups: remimazolam 0.2 mg/kg (R1 group), 0.3 mg/kg (R2 group), 0.4 mg/kg (R3 group), and propofol group (P group). All patients were anesthetized with single shots of experimental drugs during induction period. Efficacy was measured by completing the induction of anesthesia without rescue sedation; and safety was defined as no severe adverse events. RESULTS: Success induction rates in remimazolam groups were 89% (R1 group), 94% (R2 group) and 100% (R3 group) while success induction rate in P group was 100%. Hypotension rates during induction were lower in R1 group (13%) and R2 group (24%) compared with P group (44%). Hypotension rate in R3 group (34%) was similar to propofol (44%). Injection site pain in group P was 27% while no pain was observed in remimazolam groups. CONCLUSIONS: Remimazolam is a safe and effective sedative drug during induction with less adverse effects for general anesthesia in ASA I or II patients.

The TAAR1 inhibitor EPPTB suppresses neuronal excitability and seizure activity in mice.

Epilepsy is a common neurological disease. G protein-coupled receptors (GPCRs) are extensively distributed and play an important role in human health by serving as therapeutic targets for various diseases. As one of the GPCRs, trace amine-associated receptor 1 (TAAR1) has recently aroused increasing interest as a potential therapeutic target for psychiatric disorders. However, the effect of TAAR1 on epileptic seizures remains unclear. We hypothesized that TAAR1 plays an important role in epilepsy and might represent a potential therapeutic target. In this study, we analyzed a mouse epilepsy model and patients with temporal lobe epilepsy (TLE) and observed substantially increased TAAR1 expression compared with the control group. In recordings of hippocampal slices, the TAAR1-specific inhibitor N-(3-ethoxyphenyl)-4-(pyrrolidin-1-yl)-3-(trifluoromethyl) benzamide (EPPTB) suppressed the excitability of hippocampal pyramidal neurons. EPPTB also reduced seizure-like events (SLEs) and seizure activity. Our results suggest that EPPTB attenuates seizure activity and that TAAR1 might be a potential drug target for individuals with epilepsy.

Untargeted metabolomics and lipidomics uncovering the cardioprotective effects of Huanglian Jiedu Decoction on pathological cardiac hypertrophy and remodeling.

ETHNOPHARMACOLOGICAL RELEVANCE: As a classic herbal prescription, Huanglian Jiedu Decoction (HLJDD) exhibits positive effects against cardiac dysfunction. However, its cardioprotective effects and potential mechanism(s) of action still need to be systematically investigated. AIM OF THE STUDY: This study aimed to reveal the underlying therapeutic mechanism of HLJDD on transverse aortic constriction (TAC)-induced pathological cardiac hypertrophy and remodeling. MATERIALS AND METHODS: TAC-induced cardiac hypertrophy and remodeling mice model was established to evaluate the therapeutic effects of HLJDD. Serum untargeted metabolomics and lipidomic profiling were performed using ultra-performance liquid chromatography quadrupole-time-of-flight mass spectrometry coupled with multivariate statistical analyses. RESULTS: Oral administration of HLJDD (2.5 g/kg/day, 5.0 g/kg/day) significantly improved the heart morphology, enhanced the heart function, and alleviated the accumulation of fibrosis in the interstitial space and the infiltration of inflammatory cells in TAC-stimulated mice. Serum untargeted metabolomics analysis showed that significant alterations were observed in metabolic signatures between the TAC-model and sham group. Principal component analysis and orthogonal partial least-squares discriminant analysis screened 59 differential metabolic features and 13 metabolites were identified. The disturbed metabolic pathways in TAC group mainly related to lipid metabolism. Further serum lipidomic profiling showed that most lipids including cholesterol esters, ceramides, glycerides, fatty acids and phospholipids were decreased in TAC group and these alterations were reversed after HLJDD intervention. CONCLUSION: HLJDD alleviates TAC-induced pathological cardiac hypertrophy and remodeling, and its potential therapeutic mechanism involves the regulation of lipid metabolism.