Extracellular RNA Sensing Mediates Inflammation and Organ Injury in a Murine Model of Polytrauma.

Severe traumatic injury leads to marked systemic inflammation and multiorgan injury. Endogenous drivers such as extracellular nucleic acid may play a role in mediating innate immune response and the downstream pathogenesis. Here, we explored the role of plasma extracellular RNA (exRNA) and its sensing mechanism in inflammation and organ injury in a murine model of polytrauma. We found that severe polytrauma-bone fracture, muscle crush injury, and bowel ischemia-induced a marked increase in plasma exRNA, systemic inflammation, and multiorgan injury in mice. Plasma RNA profiling with RNA sequencing in mice and humans revealed a dominant presence of miRNAs and marked differential expression of numerous miRNAs after severe trauma. Plasma exRNA isolated from trauma mice induced a dose-dependent cytokine production in macrophages, which was almost abolished in TLR7-deficient cells but unchanged in TLR3-deficient cells. Moreover, RNase or specific miRNA inhibitors against the selected proinflammatory miRNAs (i.e., miR-7a-5p, miR-142, let-7j, miR-802, and miR-146a-5p) abolished or attenuated trauma plasma exRNA-induced cytokine production, respectively. Bioinformatic analyses of a group of miRNAs based on cytokine readouts revealed that high uridine abundance (>40%) is a reliable predictor in miRNA mimic-induced cytokine and complement production. Finally, compared with the wild-type, TLR7-knockout mice had attenuated plasma cytokine storm and reduced lung and hepatic injury after polytrauma. These data suggest that endogenous plasma exRNA of severely injured mice and ex-miRNAs with high uridine abundance prove to be highly proinflammatory. TLR7 sensing of plasma exRNA and ex-miRNAs activates innate immune responses and plays a role in inflammation and organ injury after trauma.

A genome-wide Drosophila screen for heat nociception identifies α2δ3 as an evolutionarily conserved pain gene.

Worldwide, acute, and chronic pain affects 20% of the adult population and represents an enormous financial and emotional burden. Using genome-wide neuronal-specific RNAi knockdown in Drosophila, we report a global screen for an innate behavior and identify hundreds of genes implicated in heat nociception, including the α2δ family calcium channel subunit straightjacket (stj). Mice mutant for the stj ortholog CACNA2D3 (α2δ3) also exhibit impaired behavioral heat pain sensitivity. In addition, in humans, α2δ3 SNP variants associate with reduced sensitivity to acute noxious heat and chronic back pain. Functional imaging in α2δ3 mutant mice revealed impaired transmission of thermal pain-evoked signals from the thalamus to higher-order pain centers. Intriguingly, in α2δ3 mutant mice, thermal pain and tactile stimulation triggered strong cross-activation, or synesthesia, of brain regions involved in vision, olfaction, and hearing.

A global in vivo Drosophila RNAi screen identifies NOT3 as a conserved regulator of heart function.

Heart diseases are the most common causes of morbidity and death in humans. Using cardiac-specific RNAi-silencing in Drosophila, we knocked down 7061 evolutionarily conserved genes under conditions of stress. We present a first global roadmap of pathways potentially playing conserved roles in the cardiovascular system. One critical pathway identified was the CCR4-Not complex implicated in transcriptional and posttranscriptional regulatory mechanisms. Silencing of CCR4-Not components in adult Drosophila resulted in myofibrillar disarray and dilated cardiomyopathy. Heterozygous not3 knockout mice showed spontaneous impairment of cardiac contractility and increased susceptibility to heart failure. These heart defects were reversed via inhibition of HDACs, suggesting a mechanistic link to epigenetic chromatin remodeling. In humans, we show that a common NOT3 SNP correlates with altered cardiac QT intervals, a known cause of potentially lethal ventricular tachyarrhythmias. Thus, our functional genome-wide screen in Drosophila can identify candidates that directly translate into conserved mammalian genes involved in heart function.

Tunable Multistate Ferroelectricity of Unit-Cell-Thick BaTiO3 Revived by a Ferroelectric SnS Monolayer via Interfacial Sliding.

Stabilization of multiple polarization states at the atomic scale is pivotal for realizing high-density memory devices beyond prevailing bistable ferroelectric architectures. Here, we show that two-dimensional ferroelectric SnS or GeSe is able to revive and stabilize the ferroelectric order of three-dimensional ferroelectric BaTiO3, even when the latter is thinned to one unit cell in thickness. The underlying mechanism for overcoming the conventional detrimental critical thickness effect is attributed to facile interfacial inversion symmetry breaking by robust in-plane polarization of SnS or GeSe. Furthermore, when invoking interlayer sliding, we can stabilize multiple polarization states and achieve efficient interstate switching in the heterostructures, accompanied by dynamical ferroelectric skyrmionic excitations. When invoking sliding and twisting, the moiré domains exhibit nontrivial polar vortexes, which can be laterally displaced via different sliding schemes. These findings provide an intuitive avenue for simultaneously overcoming the standing critical thickness issue in bulk ferroelectrics and weak polarization issue in sliding ferroelectricity.

Anatomy of Hidden Dzyaloshinskii-Moriya Interactions and Topological Spin Textures in Centrosymmetric Crystals.

The Dzyaloshinskii-Moriya interaction (DMI) is understood to be forbidden by the symmetry of centrosymmetric systems, thus restricting the candidate types for investigating many correlated physical phenomena. Here, we report the hidden DMI existing in centrosymmetric magnets driven by the local inversion symmetry breaking of specific spin sublattices. The opposite DMI spatially localized on the inverse spin sublattice favors the separated spin spiral with opposite chirality. Furthermore, we elucidate that hidden DMI widely exists in many potential candidates, from the first-principles calculations on the mature crystal database. Interestingly, novel topological spin configurations, such as the anti-chirality-locked merons and antiferromagnetic-ferromagnetic meron chains, are stabilized as a consequence of hidden DMI. Our understanding enables the effective control of DMI by symmetry operations at the atomic level and enlarges the range of currently useful magnets for topological magnetism.

Global Epidemiology of Gallstones in the 21st Century: A Systematic Review and Meta-Analysis.

BACKGROUND & AIMS: Gallstones are common and associated with substantial health and economic burden. We aimed to comprehensively evaluate the prevalence and incidence of gallstones in the 21st century. METHODS: We systematically searched PubMed and Embase to identify studies reporting the prevalence and/or incidence of gallstones between January 1, 2000, and November 18, 2023. Pooled prevalence and incidence were calculated using DerSimonian and Laird's random-effects model. We performed subgroup analyses and meta-regression based on age, sex, geographic location, population setting, and modality of detection to examine sources of heterogeneity. RESULTS: Based on 115 studies with 32,610,568 participants, the pooled prevalence of gallstones was 6.1% (95% CI, 5.6-6.5). Prevalence was higher in females vs males (7.6% vs 5.4%), in South America vs Asia (11.2% vs 5.1%), in upper-middle-income countries vs high-income countries (8.9% vs 4.0%), and with advancing age. On sensitivity analysis of population-based studies, the prevalence of gallstones was 5.5% (95% CI, 4.1-7.4; n = 44 studies), and when limiting subgroup analysis to imaging-based detection modalities, the prevalence was 6.7% (95% CI, 6.1-7.3; n = 101 studies). Prevalence has been stable over the past 20 years. Based on 12 studies, the incidence of gallstones was 0.47 per 100 person-years (95% CI, 0.37-0.51), without differences between males and females, and with increasing incidence in more recent studies. CONCLUSIONS: Globally, 6% of the population have gallstones, with higher rates in females and in South America. The incidence of gallstones may be increasing. Our findings call for prioritizing research on the prevention of gallstones.

Coronavirus GenBrowser for monitoring the transmission and evolution of SARS-CoV-2.

Genomic epidemiology is important to study the COVID-19 pandemic, and more than two million severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic sequences were deposited into public databases. However, the exponential increase of sequences invokes unprecedented bioinformatic challenges. Here, we present the Coronavirus GenBrowser (CGB) based on a highly efficient analysis framework and a node-picking rendering strategy. In total, 1,002,739 high-quality genomic sequences with the transmission-related metadata were analyzed and visualized. The size of the core data file is only 12.20 MB, highly efficient for clean data sharing. Quick visualization modules and rich interactive operations are provided to explore the annotated SARS-CoV-2 evolutionary tree. CGB binary nomenclature is proposed to name each internal lineage. The pre-analyzed data can be filtered out according to the user-defined criteria to explore the transmission of SARS-CoV-2. Different evolutionary analyses can also be easily performed, such as the detection of accelerated evolution and ongoing positive selection. Moreover, the 75 genomic spots conserved in SARS-CoV-2 but non-conserved in other coronaviruses were identified, which may indicate the functional elements specifically important for SARS-CoV-2. The CGB was written in Java and JavaScript. It not only enables users who have no programming skills to analyze millions of genomic sequences, but also offers a panoramic vision of the transmission and evolution of SARS-CoV-2.

Vitamin D May Play a Vital Role in Alleviating Type 2 Diabetes Mellitus by Modulating the Ferroptosis Signaling Pathway.

Ferroptosis is an iron-dependent death mode mediated by the aggregation of lipid peroxides and lipid-reactive oxygen species. It is characterized by iron-dependent lipid peroxide accumulation accompanied by oxidoreductase deficiency. Pancreatic beta cell dysfunction and insulin resistance are two major causes of type 2 diabetes mellitus (T2DM). Iron accumulation and metabolism may play a role in the development of T2DM. The molecular mechanism of ß cell apoptosis and iron death in T2DM were reviewed. In addition, we discuss recent insights on the relationship between the trace element iron and apoptosis of ß cells in T2DM.

Paenibacillus thermotolerans sp. nov., isolated from a hot spring in Yunnan Province, south-west China.

Two Gram-positive, rod-shaped, endospore-forming strains, YIM B05601 and YIM B05602T, were isolated from soil sampled at Hamazui hot spring, Tengchong City, Yunnan Province, PR China. Phylogenetic analysis based on 16S rRNA gene sequences suggested that the two strains fell within the genus Paenibacillus, appearing most closely related to Paenibacillus alkalitolerans YIM B00362T (96.9 % sequence similarity). Genome-based phylogenetic analysis confirmed that strains YIM B05601 and YIM B05602T formed a distinct phylogenetic cluster within the genus Paenibacillus. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values of strains YIM B05601 and YIM B05602T with the related species P. alkalitolerans YIM B00362T were within the ranges of 74.43-74.57 % and 12.1-18.5 %, respectively, which clearly indicated that strains YIM B05601, YIM B05602T represented a novel species. Strains YIM B05601 and YIM B05602T exhibited 99.6 % 16S rRNA gene sequence similarity. The ANI and dDDH values between the two strains were 99.8 and 100 %, respectively, suggesting that they belong to the same species. Optimum growth for both strains occurred at pH 7.0 and 45 °C. The diagnostic diamino acid in the cell-wall peptidoglycan of strains YIM B05601 and YIM B05602T was meso-diaminopimelic acid. MK-7 was the predominant menaquinone. The polar lipids of strain YIM B05602T were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylmonomethylethanolamine, four unidentified glycolipids, an unidentified polarlipid and phosphatidylinositol mannoside. The major fatty acids of the two stains were iso-C15 : 0 and anteiso-C15 : 0. Based on phylogenomic and phylogenetic analyses coupled with phenotypic and chemotaxonomic characterizations, strains YIM B05601 and YIM B05602T could be classified as a novel species of the genus Paenibacillus, for which the name Paenibacillus thermotolerans sp. nov. is proposed. The type strain is YIM B05602T (=CGMCC 1.60051T=KCTC 43460T=NBRC 115924T).

Coulomb blockade and Coulomb staircases in CoBi nanoislands on SrTiO3(001).

We successfully fabricated two-dimensional metallic CoBi nanoislands on SrTiO3(001) substrate by molecular beam epitaxy, and systematically investigated their electronic structures by scanning tunneling microscopy and spectroscopyin situat 4.2 K. Coulomb blockade and Coulomb staircases with discrete and well-separated levels are observed for the individual nanoisland, which is attributed to single-electron tunneling via two tunnel junction barriers. They are in excellent agreement with the simulations based on orthodox theory. Furthermore, we demonstrated that the Coulomb blockade becomes weaker with increasing temperature and almost disappears at ∼22 K in our variable temperature experiment, and its full-width at half-maximum of dI/dVpeaks with temperature is ∼6 mV. Our results provide a new platform for designing single-electron transistors that have potential applications in future microelectronics.

Description and genomic characterization of Cohnella caldifontis sp. nov., isolated from hot springs in Yunnan province, south-west China.

A bacterial strain, Gram staining positive, strictly aerobic, rod-shaped, motile bacterium with flagellum and endospore-forming, designated strain YIM B05605T, was isolated from soil sampled in Hamazui hot springs, Tengchong City, Yunnan province, China. Optimum growth for the strain occurred at pH 7.0 and 45 °C. MK-7 was the main menaquinone in the strain YIM B05605T. The diagnostic diamino acid in the cell-wall peptidoglycan was meso-diaminopimelic acid. Diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), phosphatidylethanolamine (PE), phosphatidylmonomethylethanolamine (PME), unidentified glycolipid (GL), three unknown aminophospholipids (APLs) and unidentified polarlipid (PL) were part of the polar lipid profile. The major fatty acids were anteiso-C15:0 and iso-C16:0. The DNA G + C content of the type strain was 58.76%. Genome-based phylogenetic analysis confirmed that strain YIM B05605T formed a distinct phylogenetic cluster within the genus Cohnella. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values of strain YIM B05605T with the most related species C. fontinalis YT-1101T were 73.42% and 15.7%. Functional analysis by NR, Swiss-prot, Pfam, eggNOG, GO, KEGG databases revealed that strain YIM B05605T has 13 genes related to the sulfur cycle, 2 genes related to the nitrogen cycle. Based on phylogenomic and phylogenetic analyses coupled with phenotypic and chemotaxonomic characterizations, strain YIM B05605T could be classified as a novel species of the genus Cohnella, for which the name Cohnella caldifontis sp. nov., is proposed. The type strain is YIM B05605T (= CGMCC 1.60052T = KCTC 43462T = NBRC 115921T).

Biotransformation and metabolite activity analysis of flavonoids from propolis in vivo.

Propolis is a natural resinous compound produced by bees, mixed with their saliva and wax, and has a range of biological benefits, including antioxidant and anti-inflammatory effects. This article reviews the in vivo transformation of propolis flavonoids and their potential influence on drug efficacy. Despite propolis is widely used, there is little research on how the active ingredients of propolis change in the body and how they interact with drugs. Future research will focus on these interactions and the metabolic fate of propolis in vivo.

Realization of Multiple Charge-Density Waves in NbTe2 at the Monolayer Limit.

Layered transition-metal dichalcogenides down to the monolayer (ML) limit provide a fertile platform for exploring charge-density waves (CDWs). Here, we experimentally unveil the richness of the CDW phases in ML-NbTe2 for the first time. Not only the theoretically predicted 4 × 4 and 4 × 1 phases but also two unexpected 28×28 and 19×19 phases are realized. For such a complex CDW system, we establish an exhaustive growth phase diagram via systematic efforts in the material synthesis and scanning tunneling microscope characterization. Moreover, the energetically stable phase is the larger-scale order (19×19), which is surprisingly in contradiction to the prior prediction (4 × 4). These findings are confirmed using two different kinetic pathways: i.e., direct growth at proper growth temperatures (T) and low-T growth followed by high-T annealing. Our results provide a comprehensive diagram of the "zoo" of CDW orders in ML-NbTe2.

The current status of apathy in patients with dementia and its factors: A systematic review.

OBJECTIVE: To systematically evaluate the current status of apathy in dementia patients and its associated factors. METHODS: We searched Chinese and English databases to collect studies on the associated factors of apathy in patients with dementia from inception to March 14, 2023. Two researchers independently screened the literature, evaluated the quality, and extracted the data RESULTS: A total of 20 studies were included, and the incidence of apathy in patients with dementia ranged from 21 % to 90 %. According to the model of apathy proposed by Massimo in 2018, the associated factors were divided into individual factors for dementia patients, caregiver factors, and environmental factors. The individual factors of apathy in patients with dementia mainly include demographic characteristics, the severity of cognitive impairment, a combination of other behavioral and psychological symptoms of dementia, acute medical problems or adverse drug reactions, unmet needs, and malnutrition. Caregiver factors mainly include emotional expressions of hostility or criticism towards dementia patients and caregivers' expectations for a better life in the future. Environmental factors mainly include too high or too low stimulation and a lack of daytime activities CONCLUSIONS: Existing studies have shown that the incidence of apathy in dementia patients is high and is affected by multi-dimensional factors. There are more studies on individual factors in dementia patients and fewer studies on caregivers and environmental factors. In the future, a large number of high-quality studies are needed to demonstrate the mechanism of apathy in dementia patients and to find more related factors.

[Establishment and Validation of a Predictive Model for Gallstone Disease in the General Population: A Multicenter Study]. / èƒ†ç»“çŸ³æ‚£ç— é£Žé™©é¢„æµ‹æ¨¡åž‹çš„æž„å»ºå’Œå¤šä¸­å¿ƒéªŒè¯ç ”ç©¶.

Objective: Gallstone disease (GSD) is one of the common digestive tract diseases with a high worldwide prevalence. The effects of GSD on patients include but are not limited to the symptoms of nausea, vomiting, and biliary colic directly caused by GSD. In addition, there is mounting evidence from cohort studies connecting GSD to other conditions, such as cardiovascular diseases, biliary tract cancer, and colorectal cancer. Early identification of patients at a high risk of GSD may help improve the prevention and control of the disease. A series of studies have attempted to establish prediction models for GSD, but these models could not be fully applied in the general population due to incomplete prediction factors, small sample sizes, and limitations in external validation. It is crucial to design a universally applicable GSD risk prediction model for the general population and to take individualized intervention measures to prevent the occurrence of GSD. This study aims to conduct a multicenter investigation involving more than 90000 people to construct and validate a complete and simplified GSD risk prediction model. Methods: A total of 123634 participants were included in the study between January 2015 and December 2020, of whom 43929 were from the First Affiliated Hospital of Chongqing Medical University (Chongqing, China), 11907 were from the First People's Hospital of Jining City (Shandong, China), 1538 were from the Tianjin Medical University Cancer Institute and Hospital (Tianjin, China), and 66260 were from the People's Hospital of Kaizhou District (Chongqing, China). After excluding patients with incomplete clinical medical data, 35976 patients from the First Affiliated Hospital of Chongqing Medical University were divided into a training data set (n=28781, 80%) and a validation data set (n=7195, 20%). Logistic regression analyses were performed to investigate the relevant risk factors of GSD, and a complete risk prediction model was constructed. Factors with high scores, mainly according to the nomograms of the complete model, were retained to simplify the model. In the validation data set, the diagnostic accuracy and clinical performance of these models were validated using the calibration curve, area under the curve (AUC) of the receiver operating characteristic curve, and decision curve analysis (DCA). Moreover, the diagnostic accuracy of these two models was validated in three other hospitals. Finally, we established an online website for using the prediction model (The complete model is accessible at https://wenqianyu.shinyapps.io/Completemodel/, while the simplified model is accessible at https://wenqianyu.shinyapps.io/Simplified/). Results: After excluding patients with incomplete clinical medical data, a total of 96426 participants were finally included in this study (35876 from the First Affiliated Hospital of the Chongqing Medical University, 9289 from the First People's Hospital of Jining City, 1522 from the Tianjin Medical University Cancer Institute, and 49639 from the People's Hospital of Kaizhou District). Female sex, advanced age, higher body mass index, fasting plasma glucose, uric acid, total bilirubin, gamma-glutamyl transpeptidase, and fatty liver disease were positively associated with risks for GSD. Furthermore, gallbladder polyps, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and aspartate aminotransferase were negatively correlated to risks for GSD. According to the nomograms of the complete model, a simplified model including sex, age, body mass index, gallbladder polyps, and fatty liver disease was constructed. All the calibration curves exhibited good consistency between the predicted and observed probabilities. In addition, DCA indicated that both the complete model and the simplified model showed better net benefits than treat-all and treat-none. Based on the calibration plots, DCA, and AUCs of the complete model (AUC in the internal validation data set=74.1% [95% CI: 72.9%-75.3%], AUC in Shandong=71.7% [95% CI: 70.6%-72.8%], AUC in Tianjin=75.3% [95% CI: 72.7%-77.9%], and AUC in Kaizhou=72.9% [95% CI: 72.5%-73.3%]) and the simplified model (AUC in the internal validation data set=73.7% [95% CI: 72.5%-75.0%], AUC in Shandong=71.5% [95% CI: 70.4%-72.5%], AUC in Tianjin=75.4% [95% CI: 72.9%-78.0%], and AUC in Kaizhou=72.4% [95% CI: 72.0%-72.8%]), we concluded that the complete and simplified risk prediction models for GSD exhibited excellent performance. Moreover, we detected no significant differences between the performance of the two models (P>0.05). We also established two online websites based on the results of this study for GSD risk prediction. Conclusions: This study innovatively used the data from 96426 patients from four hospitals to establish a GSD risk prediction model and to perform risk prediction analyses of internal and external validation data sets in four cohorts. A simplified model of GSD risk prediction, which included the variables of sex, age, body mass index, gallbladder polyps, and fatty liver disease, also exhibited good discrimination and clinical performance. Nonetheless, further studies are needed to explore the role of low-density lipoprotein cholesterol and aspartate aminotransferase in gallstone formation. Although the validation results of the complete model were better than those of the simplified model to a certain extent, the difference was not significant even in large samples. Compared with the complete model, the simplified model uses fewer variables and yields similar prediction and clinical impact. Hence, we recommend the application of the simplified model to improve the efficiency of screening high-risk groups in practice. The use of the simplified model is conducive to enhancing the self-awareness of prevention and control in the general population and early intervention for GSD.

[Intestinal absorption components and absorption characteristics of Wuwei Qingzhuo San by everted intestinal sac models].

This study investigated the absorption profile of Wuwei Qingzhuo San in different intestinal segments and the absorption characteristics of its alkaloids(piperine, piperanine, piperlonguminine, and dihydropiperlonguminine). The everted gut sac model was established, and the chemical components of Wuwei Qingzhuo San in different intestinal segments were detected by UPLC-Q-TOF-MS. The content of piperine, piperanine, piperlonguminine, and dihydropiperlonguminine in intestinal absorption fluid was determined by UPLC-Q-TRAP-MS and the absorption parameters were calculated. The absorption characteristics in different intestinal segments at different time were analyzed. As a result, 27, 27, 8, and 6 absorbent components from Wuwei Qingzhuo San were detected in the intestinal cyst fluid of jejunum, ileum, duodenum, and colon by UPLC-Q-TOF-MS technology, respectively. It was also found that piperine, piperanine, piperlonguminine, and dihydropiperlonguminine from Wuwei Qingzhuo San showed linear absorption in various intestinal segments, with r values exceeding 0.9. In terms of absorption content, the components were ranked as piperine>piperanine>dihydropiperlonguminine>piperlonguminine in various intestinal segments, but the absorption rate and mechanism of each component varied. The results demonstrate that the absorption of the components of Wuwei Qingzhuo San in different intestinal segments is selective and is not a simple semi-permeable membrane permeation process.

[Effects of tetramethylpyrazine on pharmacokinetics in plasma and brain dialysate and neuropathic pain in rat model of spared sciatic nerve injury].

This study aims to explore the effects of tetramethylpyrazine(TMP) on pharmacokinetics in plasma and brain dialysate and neuropathic pain in the rat model of partial sciatic nerve injury(SNI), and to investigate the correlation between the analgesic effect of TMP and its concentrations in the plasma and brain dialysate. Male SD rats were randomized into Sham, SNI, and SNI+TMP groups. Mechanical stimulation with von frey filaments and cold spray method were employed to evaluate the mechanical sensitivity and cold sensitivity of rats. Another two groups, Sham+TMP and SNI+TMP, were used to intubate the common jugular vein and implant microdialysis probes into the anterior cingulate gyrus(ACC), respectively.After intraperitoneal injection of TMP at a dose of 80 mg·kg~(-1), automatic blood collection and intracerebral microdialysis(perfusion rate of 1 µL·min~(-1)) systems were used to collect the blood and brain dialysate for 24 h. HSS T3 C_(18) reversed-phase chromatographic column(2.1 mm×50 mm, 2.5 µm) was used for liquid chromatographic separation. Gradient elution was carried out with the mobile phase of methanol-water(containing 0.005% formic acid) at a flow rate of 0.25 mL·min~(-1). Electrospray ion source was used for mass spectrometry, and the scanning mode was multi-reaction monitoring under the positive ion mode. The ion pairs for quantitative analysis were TMP m/z 137/122 and aspirin m/z 179/137, respectively. DAS 2.11 was used to calculate the pharmacokinetic parameters. The optimal time of TMP to exert the analgesia effect and inhibit cold pain sensitivity was 60 min after treatment. The TMP in the plasma and brain dialysate of SNI rats showed the T_(max) of 15 min and 30 min, the C_(max) of(2 866.43±135.39) and(1 462.14±197.38) µg·L~(-1), the AUC_(0-t) of(241 463.30±28 070.31) and(213 115.62±32 570.07) µg·min·L~(-1), the MRT_(0-t) of(353.13±47.73) and(172.16±12.72) min, and the CL_Z of 0.73 and 0.36 L·min·kg~(-1), respectively. The analgesic effect of TMP had a significant correlation with the blood drug concentration in the ACC, which indicated that this method was suitable for the detection of TMP in rat plasma and brain dialysate. The method is accurate, reliable, and sensitive and can realize the important value of the application of correlation analysis theory of "automatic blood collection-microdialysis/PK-PD" in the research on neuropathic pain.

Vitamin D may alleviate pre-eclampsia by modulating the ferroptosis signalling pathway: A hypothesis based on recent literature.

Ferroptosis is a novel form of regulated cell death typically characterized by non-apoptotic, iron-dependent, and reactive accumulation of oxygen species. Recent studies have found that ferroptosis plays an important role in the pathophysiology of pre-eclampsia (PE). In order to find potential therapeutic targets for ferroptosis intervention and better prevent the occurrence and progression of PE, the signalling pathways that regulate ferroptosis need to be identified. In this article, we review the role of vitamin D in PE and the role of ferroptosis in PE. Based on recent literature, we propose the scientific hypothesis that vitamin D can alleviate preeclampsia by modulating the ferroptosis signalling pathway. The aim of this review is to understand the regulatory pathways of ferroptosis in PE and to identify potential therapeutic targets.

Narrative review of ferroptosis in obesity.

Obesity is widely recognized as a major global health problem caused by a chronic energy imbalance resulting from a combination of excess caloric intake and insufficient energy expenditure. Excessive energy intake and physical inactivity are traditional risk factors for obesity. Obesity is a risk factor for many diseases, including hypertension, diabetes and tumours. Recent studies have found a strong link between ferroptosis and obesity. Ferroptosis is an iron-dependent regulated cell death caused by iron overload and reactive oxygen species-dependent excessive accumulation of lipid peroxidation. Ferroptosis is involved in many biological processes, such as amino acid metabolism, iron metabolism and lipid metabolism. Some potential strategies to reduce the adverse effects of ferroptosis on obesity are suggested and future research priorities are highlighted.

African Suid Genomes Provide Insights into the Local Adaptation to Diverse African Environments.

African wild suids consist of several endemic species that represent ancient members of the family Suidae and have colonized diverse habitats on the African continent. However, limited genomic resources for African wild suids hinder our understanding of their evolution and genetic diversity. In this study, we assembled high-quality genomes of a common warthog (Phacochoerus africanus), a red river hog (Potamochoerus porcus), as well as an East Asian Diannan small-ear pig (Sus scrofa). Phylogenetic analysis showed that common warthog and red river hog diverged from their common ancestor around the Miocene/Pliocene boundary, putatively predating their entry into Africa. We detected species-specific selective signals associated with sensory perception and interferon signaling pathways in common warthog and red river hog, respectively, which contributed to their local adaptation to savannah and tropical rainforest environments, respectively. The structural variation and evolving signals in genes involved in T-cell immunity, viral infection, and lymphoid development were identified in their ancestral lineage. Our results provide new insights into the evolutionary histories and divergent genetic adaptations of African suids.