Traditional Chinese medicine interventions based on meridian theory for pain relief in patients with primary dysmenorrhea: a systematic review and network meta-analysis.

Objective: To determine the comparative effects and safety of traditional Chinese medicine (TCM) interventions based on meridian theory for pain relief in patients with primary dysmenorrhea (PD). Methods: This is a systematic review with network meta-analysis. Randomized controlled trials (RCTs) comparing meridian-based TCM interventions with waitlist, placebo, western medicine, and conventional therapies for PD pain. A SUCRA was used to estimate the probability ranking for the effects of interventions. Results: 57 RCTs involving 3,903 participants and 15interventions were included. Thirty-two RCTs were rated as low risk of bias. A network diagram was drawn with 105 pairs of comparisons. Compared with NSAIDs and waitlist, significantly better effects were found in acupressure [SMD = -1.51, 95%CI (-2.91, -0.12)/SMD = -2.31, 95%CI (-4.61, -0.02)], warm needling [SMD = -1.43, 95%CI (-2.68, -0.18)/SMD = -2.23, 95%CI (-4.43, -0.03)], moxibustion [SMD = -1.21, 95%CI (-1.85, -0.57)/SMD = -2.10, 95%CI (-3.95, -0.07)], and acupuncture [SMD = -1.09, 95%CI (-1.62, -0.55)/SMD = -1.89, 95%CI (-3.67, -0.11)]. No adverse events were detected. Conclusion: For PD pain, the effects of acupressure, acupuncture, warm needling, and moxibustion were superior to those of NSAIDs and waitlist. Oral contraceptive pill, electro-acupuncture, acupressure, and warm needling demonstrated higher probabilities of being better interventions. More high-quality clinical trials are needed to provide more robust evidence of this network. Systematic review registration: PROSPERO CRD42022373312.

Integration of Diffusion Transformer and Knowledge Graph for Efficient Cucumber Disease Detection in Agriculture.

In this study, a deep learning method combining knowledge graph and diffusion Transformer has been proposed for cucumber disease detection. By incorporating the diffusion attention mechanism and diffusion loss function, the research aims to enhance the model's ability to recognize complex agricultural disease features and to address the issue of sample imbalance efficiently. Experimental results demonstrate that the proposed method outperforms existing deep learning models in cucumber disease detection tasks. Specifically, the method achieved a precision of 93%, a recall of 89%, an accuracy of 92%, and a mean average precision (mAP) of 91%, with a frame rate of 57 frames per second (FPS). Additionally, the study successfully implemented model lightweighting, enabling effective operation on mobile devices, which supports rapid on-site diagnosis of cucumber diseases. The research not only optimizes the performance of cucumber disease detection, but also opens new possibilities for the application of deep learning in the field of agricultural disease detection.

[Effects of Nitrogen Addition on Soil Organic Carbon and Its Fractions in Karst Farmland and Forest Ecosystems of China Based on Meta-analysis].

In recent decades, with the intensification of human activities, atmospheric nitrogen （N） deposition has been increasing. N deposition affects carbon （C） cycling in terrestrial ecosystems, especially in fragile karst ecosystems. Karst ecosystems are considered to be an important C pool. To evaluate the impact of N deposition on soil organic C （SOC） and its fractions in karst ecosystems of China, we collected and collated 14 English literature published through the end of March 2023, yielding a total of 460 sets of experimental data. The meta-analysis examined the effect of N addition levels [low N: ≤50 kg·ï¼ˆhm2·a）-1, medium N: 50-100 kg·ï¼ˆhm2·a）-1, and high N: >100 kg·ï¼ˆhm2·a）-1, in terms of N] on SOC and its fractions [particular organic C （POC）, readily oxidized organic C （ROC）, microbial biomass C （MBC）, and dissolved organic C （DOC）]. The results showed that N addition levels significantly affected the responses of farmland and forest soil SOC and their active fractions to N addition. Specifically, low and high N additions significantly increased SOC concentration in farmland ecosystems, whereas medium N addition significantly increased SOC concentration in forest ecosystems. In addition, soil active C fraction concentrations increased under high N addition in farmland ecosystems and under low and medium N addition in forest ecosystems. Without considering the level of N addition, N addition significantly enhanced soil organic matter （SOM） mineralization in both farmland and forest ecosystems and increased the SOC concentration in farmland ecosystems but not forest ecosystems. The responses of different active C fractions to N addition were diverse. In farmland ecosystems, the POC and ROC concentrations increased, but DOC did not change with N addition. In forest ecosystems, the DOC and POC concentrations increased, but there was no significant effect on MBC. Moreover, the response ratios （RR） of SOC and its fractions in different ecosystems to N addition were influenced by different environmental factors. In farmland ecosystems, the response ratio of SOC was related to the annual average temperature and soil pH. The response ratio of DOC was affected by the annual average temperature, mean annual precipitation, and N addition rate. The POC response ratio was related to the N addition rate. In forest ecosystems, the effects of N addition on the SOC response ratio were significantly altered by the annual average temperature, mean annual precipitation, and soil pH. However, the response ratios of DOC, POC, and MBC were not affected by the annual average temperature, mean annual precipitation, soil pH, and N addition rate. Consequently, these findings indicate that N addition could enhance soil SOC concentration and promote soil C sequestration in farmland and forest ecosystems in karst regions, but this effect relies on the level of N addition. This provides a scientific basis for predicting the soil C sink function in karst ecosystems under climate change scenarios.

Ultrahigh Pyridinic/Pyrrolic N Enabling N/S Co-Doped Holey Graphene with Accelerated Kinetics for Alkali-Ion Batteries.

Carbonaceous materials hold great promise for K-ion batteries due to their low cost, adjustable interlayer spacing, and high electronic conductivity. Nevertheless, the narrow interlayer spacing significantly restricts their potassium storage ability. Herein, hierarchical N, S co-doped exfoliated holey graphene (NSEHG) with ultrahigh pyridinic/pyrrolic N (90.6 at.%) and large interlayer spacing (0.423 nm) is prepared through micro-explosion assisted thermal exfoliation of graphene oxide (GO). The underlying mechanism of the micro-explosive exfoliation of GO is revealed. The NSEHG electrode delivers a remarkable reversible capacity (621 mAh g-1 at 0.05 A g-1), outstanding rate capability (155 mAh g-1 at 10 A g-1), and robust cyclic stability (0.005% decay per cycle after 4400 cycles at 5 A g-1), exceeding most of the previously reported graphene anodes in K-ion batteries. In addition, the NSEHG electrode exhibits encouraging performances as anodes for Li-/Na-ion batteries. Furthermore, the assembled activated carbon||NSEHG potassium-ion hybrid capacitor can deliver an impressive energy density of 141 Wh kg-1 and stable cycling performance with 96.1% capacitance retention after 4000 cycles at 1 A g-1. This work can offer helpful fundamental insights into design and scalable fabrication of high-performance graphene anodes for alkali metal ion batteries.

ST-GEARS: Advancing 3D downstream research through accurate spatial information recovery.

Three-dimensional Spatial Transcriptomics has revolutionized our understanding of tissue regionalization, organogenesis, and development. However, existing approaches overlook either spatial information or experiment-induced distortions, leading to significant discrepancies between reconstruction results and in vivo cell locations, causing unreliable downstream analysis. To address these challenges, we propose ST-GEARS (Spatial Transcriptomics GEospatial profile recovery system through AnchoRS). By employing innovative Distributive Constraints into the Optimization scheme, ST-GEARS retrieves anchors with exceeding precision that connect closest spots across sections in vivo. Guided by the anchors, it first rigidly aligns sections, next solves and denoises Elastic Fields to counteract distortions. Through mathematically proved Bi-sectional Fields Application, it eventually recovers the original spatial profile. Studying ST-GEARS across number of sections, sectional distances and sequencing platforms, we observed its outstanding performance on tissue, cell, and gene levels. ST-GEARS provides precise and well-explainable 'gears' between in vivo situations and in vitro analysis, powerfully fueling potential of biological discoveries.

A sugary solution: Harnessing polysaccharide-based materials for osteoporosis treatment.

Osteoporosis, a prevalent skeletal disorder characterized by diminished bone density, compromised microstructure, and heightened fracture susceptibility, poses a growing public health concern exacerbated by aging demographics. Polysaccharides-based materials, derived from a diverse range of sources, exhibit exceptional biocompatibility. They possess a structure similar to the extracellular matrix, which can enhance cell adhesion in vivo, and demonstrate superior biological activity compared to artificial materials. This study delved into an in-depth examination of the various biomaterials and polysaccharide families associated with the treatment of osteoporosis. This article elucidates the benefits and attributes of polysaccharide-based materials in contrast to current clinical treatment modalities, delineating how these materials address prevalent challenges in the clinical management of osteoporosis. An overview of the prospective applications of polysaccharide-based materials in the future is also provided, as well as outlines the challenges that should be addressed prior to the clinical implementation of such materials.

Molecular-level insights into the brewing-dependent chemical diversity, properties, and formation mechanism of Moutai Base baijiu using Fourier transform ion cyclotron resonance mass spectrometry.

The brewing-dependent molecular diversity, properties, and formation mechanism of Moutai (a typical sauce-flavor Baijiu) base Baijiu, were explored using FT-ICR MS combined with various visualization methods. Seven-round Moutai base Baijiu exhibited significant diversity and heterogeneity, containing more unsaturated/saturated reduced molecules. The increased brewing round increased the molecular unsaturation/aromaticity and enhanced the transformation between saturated/oxidized and unsaturated/reduced molecules. Moreover, lignin-/aliphatic-/peptide-/lipid-like molecules dominated the molecular characteristics of Moutai base Baijiu. The basic and acidic components contained more reduced carbohydrate-/lipid-like molecules and oxidized tannin-like/condensed aromatic molecules, respectively, contributing to the molecular stability and diversity, respectively. More unique lipid-like and lignin-like molecules newly formed in the early and late brewing rounds, respectively, and the increased brewing shifted the chemical reaction from a single dominant to a multi-dimensional balance. More unique N-containing molecules (>450 Da) significantly contributed the specific brewing characteristics. These new findings help to understand the molecular-level formation mechanism of Moutai base Baijiu.

Enhancing Rapid Li+/Na+ Storage Performance via Interface Engineering of Reduced Graphene Oxide-Wrapped Bimetallic Sulfide Nanocages.

Transition-metal sulfide is considered to be an admirable transformational electrode material due to low cost, large specific capacity, and good reversibility in lithium-ion batteries (LIBs) and sodium-ion batteries (SIBs). Herein, the reduced graphene oxide-wrapped open bimetallic sulfide (NiS2-Co3S4@rGO) nanocage, derived from nickel-cobalt Prussian blue, was obtained by two-step calcination. There are luxuriant pore structures in the nanocage composite with a specific surface area of 85.28 m2 g-1, which provides plentiful paths for rapid transmission of Li+/Na+ and alleviates the volume stress caused by insertion and extraction of alkali metal ions. The excellent interface combination of bimetallic sulfide wrapped in reduced graphene oxide improves the conductivity and overall performance of the battery. Thanks to the special interface engineering, the open NiS2-Co3S4@rGO nanocage composite displays rapid lithium storage properties with an average diffusion coefficient of 8.5 × 10-13 cm2 s-1. Moreover, after 300 cycles, the reversible capacity of the composite is 1113.2 mAh g-1 at 1 A g-1. In SIBs, the capacity of the open NiS2-Co3S4@rGO composite is 487.9 mAh g-1 when the current density is 5 A g-1. These preeminent performances demonstrate the enormous development prospects of bimetallic sulfide nanocage as anode material in LIBs and SIBs.

Donor-Acceptor Type Supra-Carbon-Dots with Long Lifetime Photogenerated Radicals Boosting Tumor Photodynamic Therapy.

Carbon dots (CDs) have gained significant interest because of their potential in biomedical applications. Nevertheless, developing CDs with efficient photoinduced charge separation for tumor photodynamic therapy (PDT) remains a challenge. This study presents a novel class of supra-carbon-dots (supra-CDs) developed by fusing red emissive CDs with 2,3-dicyanohydroquinone (DCHQ) via post-solvothermal treatment. In supra-CDs, the core, acting as electron donors, is formed by assembled CDs with substantial sp2 domains, the fused interface originating from DCHQ with electron-withdrawing groups functions as the electron acceptor. This configuration creates the unique donor-acceptor nanostructure. Upon white light irradiation, the excited electrons from the assembled CDs were transferred to the electron-withdrawing interface, whereas the photogenerated holes were retained within the assembled CDs as radicals, leading to effective photoinduced charge separation. The separated photogenerated electrons then react with oxygen to generate superoxide radicals. Simultaneously, the photogenerated holes undergo oxidation of crucial cellular substrates. This dual action underscores the exceptional cell-killing efficacy of supra-CDs. Moreover, the increased particle sizes (~20 nm) ensure supra-CDs to exhibit a notable capacity for tumor accumulation via the improved permeability and retention effect, thereby achieving satisfactory anti-tumor PDT efficacy in a mouse subcutaneous tumor model.

Nickel coating on plasmonic copper nanoparticles lowers cytotoxicity and enables colorimetric pH readout for antibacterial wound dressing application.

Wound infection poses a significant challenge to the natural healing process. It can impede various stages of wound healing, thereby hindering tissue regeneration and increasing the risk of systemic complications. Wound dressings emerged as a crucial option in the management of infections. Herein, we investigate fabrics coated with copper-based nanoparticles for potential wound dressing application. We synthesized copper and copper-nickel (Cu-Ni) core-shell nanoparticles via a polyol synthesis and investigated their particle growth dynamics and chemical stability. The nickel coating stabilized the nanoparticles against oxidation and dissolution, while dampening the localized surface plasmon resonance of copper. When coated on the fabrics, we found that Cu-Ni NPs were slightly less effective as an antibacterial agent than Cu NPs, however the cytotoxicity of Cu-Ni NPs was significantly reduced compared to pure Cu. Additionally, we show that the discoloration of nanoparticle-coated fabrics depended on pH, thus enabling the visualization of pH levels of simulated wound fluids which can provide information on the inflammatory state of the wound. Our work contributes to the understanding of copper-based nanoparticles and their potential applications in healthcare.

Microsurgical clipping versus endovascular therapy for treating patients with middle cerebral artery aneurysms presenting with neurological ischemic symptoms.

Studies comparing different treatment methods in patients with middle cerebral artery (MCA) aneurysms in different subgroups of onset symptoms are lacking. It is necessary to explore the safety and efficacy of open surgical treatment and endovascular therapy in patients with MCA aneurysms in a specific population. This study aimed to compare microsurgical clipping versus endovascular therapy regarding complication rates and outcomes in patients with MCA aneurysms presenting with neurological ischemic symptoms. This was a retrospective cohort study in which 9656 patients with intracranial aneurysms were screened between January 2014 and July 2022. Further, 130 eligible patients were enrolled. The primary outcome was the incidence of serious adverse events (SAEs) within 30 days of treatment, whereas secondary outcomes included postprocedural target vessel-related stroke, disabling stroke or death, mortality, and aneurysm occlusion rate. Among the 130 included patients, 45 were treated with endovascular therapy and 85 with microsurgical clipping. The primary outcome of the incidence of SAEs within 30 days of treatment was significantly higher in the clipping group [clipping: 23.5%(20/85) vs endovascular: 8.9%(4/45), adjusted OR:4.05, 95% CI:1.20-13.70; P = 0.024]. The incidence of any neurological complications related to the treatment was significantly higher in the clipping group [clipping:32.9%(28/85) vs endovascular:15.6%(7/45); adjusted OR:3.49, 95%CI:1.18-10.26; P = 0.023]. Postprocedural target vessel-related stroke, disabling stroke or death, mortality rate, and complete occlusion rate did not differ significantly between the two groups. Endovascular therapy seemed to be safer in treating patients with MCA aneurysms presenting with neurological ischemic symptoms compared with microsurgical clipping, with a significantly lower incidence of SAEs within 30 days of treatment and any neurological complications related to the treatment during follow-up.

Type 2 diabetes microenvironment promotes the development of Parkinson's disease by activating microglial cell inflammation.

Objective: Parkinson's disease (PD) is the second most common neurodegenerative disease in the world, and type 2 diabetes (T2DM) and PD are influenced by common genetic and environmental factors. Mitochondrial dysfunction and inflammation are common pathogenic mechanisms of both diseases. However, the close association between PD and T2DM and the specific relationship between them are not yet clear. This study aimed to reveal the specific connection between the two diseases by establishing a mouse model of comorbid PD and T2DM, as well as a Bv2 cell model. Methods: C57BL/6 mouse were used to construct a model of PD with T2DM using streptozotocin and rotenone, while Bv2 cells were used to simulate the microenvironment of PD and T2DM using rotenone and palmitate. Behavioral tests were conducted to assess any differences in motor and cognitive functions in mouse. Immunohistochemistry was used to analyze the number of dopaminergic neurons in the substantia nigra region of mouse. Western blotting was used to detect the expression levels of TH, P-NFκB, NFκB, Cyclic GMP-AMP synthase (cGAS), and Stimulator of interferon genes (STING) proteins in the substantia nigra region of mouse and Bv2 cells. qRT-PCR was used to analyze the expression levels of IL1ß, IL6, and TNF-α. Seahorse technology was used to assess mitochondrial function in Bv2 cells. Results: T2DM exacerbated the motor and cognitive symptoms in mouse with PD. This effect may be mediated by disrupting mitochondrial function in microglial cells, leading to damaged mtDNA leakage into the cytoplasm, subsequently activating the cGAS-STING pathway and downstream P-NFκB/NFκB proteins, triggering an inflammatory response in microglial cells. Microglial cells release inflammatory factors such as IL1ß, IL6, and TNF-α, exacerbating neuronal damage caused by PD. Conclusion: Our study results suggest that T2DM may exacerbate the progression of PD by damaging mitochondrial function, and activating microglial cell inflammation. The detrimental effects on Parkinson's disease may be achieved through the activating of the cGAS-STING protein pathway.

Harnessing Health Information Technology in Domestic Violence in the United States: A Scoping Review.

Objectives: The following scoping review aims to identify and map the existing evidence for HIT interventions among women with DV experiences in the United States. And provide guidance for future research, and facilitate clinical and technical applications for healthcare professionals. Methods: Five databases, PubMed, EBSCOhost CINAHL, Ovid APA PsycINFO, Scopus and Google Scholar, were searched from date of inception to May 2023. Reviewers extracted classification of the intervention, descriptive details, and intervention outcomes, including physical safety, psychological, and technical outcomes, based on representations in the included studies. Results: A total of 24 studies were included, identifying seven web-based interventions and four types of abuse. A total of five studies reported safety outcomes related to physical health. Three studies reported depression, anxiety, and post-traumatic stress disorder as psychological health outcomes. The effectiveness of technology interventions was assessed in eight studies. Conclusion: Domestic violence is a major public health issue, and research has demonstrated the tremendous potential of health information technology, the use of which can support individuals, families, and communities of domestic violence survivors.

Efficient wideband tunable radio frequency-optical conversion via triply resonant photonic molecules.

Electro-optic (EO) transduction of weak radio frequency (RF) and millimeter-wave signals, such as those received by an antenna, onto laser sidebands for processing in the optical domain requires efficient EO modulators. Microrings offer spatial density and efficiency advantages over Mach-Zehnder modulators (MZMs), but conventional single-ring modulators suffer a fundamental trade-off between resonantly enhanced conversion efficiency and the RF carrier frequency that it can accommodate. Dual-cavity "photonic molecule" modulators resolve this trade-off, allowing high efficiency independent of the RF carrier frequency by providing separate resonant supermodes to enhance the laser local oscillator (LO) and the narrowband RF-detuned sideband. However, the RF frequency is fixed at design time by geometry, with efficiency dropping quickly for RF carriers away from the design value. We propose a novel, to the best of our knowledge, triple-cavity configuration with an off-resonant middle ring acting as an effective tunable coupler between two active modulator cavities. This configuration provides wideband tunability of the target RF carrier while maintaining efficient sideband conversion. When the middle ring is passive (high Q), this configuration provides wide RF tunability with no efficiency penalty over the fixed dual-cavity case and could become an important building block for future RF/mm-wave photonic integrated circuits (PICs).

Construction of an Ohmic Contact Cathode by Two Metal Sulfides for efficient Capture and Catalysis of Polysulfide.

The slow reaction kinetics and severe shuttle effect of lithium polysulfide make Li-S battery electrochemical performance difficult to meet the demands of large electronic devices such as electric vehicles. Based on this, an electrocatalyst constructed by metal phase material (MoS2) and semiconductor phase material (SnS2) with ohmic contact is designed for inhibiting the dissolution of lithium polysulfide with improving the reaction kinetics. According to the density-functional theory calculations, it is found that the heterostructured samples with ohmic contacts can effectively reduce the reaction-free energy of lithium polysulfide to accelerate the sulfur redox reaction, in addition to the excellent electron conduction to reduce the overall activation energy. The metallic sulfide can add more sulfophilic sites to promote the capture of polysulfide. Thanks to the ohmic contact design, the carbon nanotube-MoS2-SnS2 achieved a specific capacity of 1437.2 mAh g-1 at 0.1 C current density and 805.5 mAh g-1 after 500 cycles at 1 C current density and is also tested as a pouch cell, which proves to be valuable for practical applications. This work provides a new idea for designing an advanced and efficient polysulfide catalyst based on ohmic contact.

Predicting the Information Need for Domestic Violence Survivors Based on the Fine-Tuned Large Language Model.

Women with domestic violence experiences often refuse to seek help face-to-face due to embarrassment. They begin to share their emotions and seek help from online health communities. Understanding and responding to these posts can be crucial in providing timely support to the victims. We proposed a fine-tuned large language model (LLM) capable of accurately predicting the informational need based on the content of postings. We fine-tuned the LAMMA2-7B-chat model based on the guidance of identifying the information need and a dataset comprising 273 posts from Reddit, which are manually annotated by domain experts. Furthermore, we evaluated the performance of our model using a random sample of 15 posts, and 66.6% were accurately predicted. The results demonstrate that our model can rapidly capture the information needs expressed in the posts, enabling healthcare providers to provide timely and useful support based on our predictions.

Regulate the Solvation Structure and Interface by Nitrate in Phosphate-Based Electrolytes for 4.5 V-Class Ni-Rich Batteries.

Phosphate-based electrolyte propels the advanced battery system with high safety. Unfortunately, restricted by poor electrochemical stability, it is difficult to be compatible with advanced lithium metal anodes and Ni-rich cathodes. To alleviate these issues, the study has developed a phosphate-based localized high-concentration electrolyte with a nitrate-driven solvation structure, and the nitrate-derived N-rich inorganic interface shows excellent performance in stabilizing the LiNi0.8Co0.1Mn0.1O2 (NCM811) cathode interface and modulating the lithium deposition morphology on the anode. The results show that the Li|| NCM811 cell has exceptional long-cycle stability of >80% capacity retention after 800 cycles at 4.3 V, 1 C. A more prominent capacity retention rate of 93.3% after 200 cycles can be reached with the high voltage of 4.5 V. While being compatible with the phosphate-based electrolyte with good flame retardancy and the good electrochemical stability of Ni-rich lithium metal battery (LMBs) systems, the present work expands the construction of anion-rich solvation structures, which is expected to promote the development of the high-performance LMBs with safety.

The causal relationship and potential mediators between plasma lipids and atopic dermatitis: a bidirectional two-sample, two-step mendelian randomization.

BACKGROUND: Observational studies have indicated that the plasma lipid profiles of patients with atopic dermatitis show significant differences compared to healthy individuals. However, the causal relationship between these differences remains unclear due to the inherent limitations of observational studies. Our objective was to explore the causal effects between 179 plasma lipid species and atopic dermatitis, and to investigate whether circulating inflammatory proteins serve as mediators in this causal pathway. METHODS: We utilized public genome-wide association studies data to perform a bidirectional two-sample, two-step mendelian randomization study. The inverse variance-weighted method was adopted as the primary analysis technique. MR-Egger and the weighted median were used as supplementary analysis methods. MR-PRESSO, Cochran's Q test, and MR-Egger intercept test were applied for sensitivity analyses to ensure the robustness of our findings. RESULTS: The Mendelian randomization analysis revealed that levels of Phosphatidylcholine (PC) (18:1_20:4) (OR: 0.950, 95% CI: 0.929-0.972, p = 6.65 × 10- 6), Phosphatidylethanolamine (O-18:1_20:4) (OR: 0.938, 95% CI: 0.906-0.971, p = 2.79 × 10- 4), Triacylglycerol (TAG) (56:6) (OR: 0.937, 95% CI: 0.906-0.969, p = 1.48 × 10- 4) and TAG (56:8) (OR: 0.918, 95% CI: 0.876-0.961, p = 2.72 × 10- 4) were inversely correlated with the risk of atopic dermatitis. Conversely, PC (18:1_20:2) (OR: 1.053, 95% CI: 1.028-1.079, p = 2.11 × 10- 5) and PC (O-18:1_20:3) (OR: 1.086, 95% CI: 1.039-1.135, p = 2.47 × 10- 4) were positively correlated with the risk of atopic dermatitis. The results of the reverse directional Mendelian randomization analysis indicated that atopic dermatitis exerted no significant causal influence on 179 plasma lipid species. The level of circulating IL-18R1 was identified as a mediator for the increased risk of atopic dermatitis associated with higher levels of PC (18:1_20:2), accounting for a mediation proportion of 9.07%. CONCLUSION: Our research suggests that plasma lipids can affect circulating inflammatory proteins and may serve as one of the pathogenic factors for atopic dermatitis. Targeting plasma lipid levels as a treatment for atopic dermatitis presents a potentially novel approach.

Comprehensive Identification and Characterization of HML-9 Group in Chimpanzee Genome.

Endogenous retroviruses (ERVs) are related to long terminal repeat (LTR) retrotransposons, comprising gene sequences of exogenous retroviruses integrated into the host genome and inherited according to Mendelian law. They are considered to have contributed greatly to the evolution of host genome structure and function. We previously characterized HERV-K HML-9 in the human genome. However, the biological function of this type of element in the genome of the chimpanzee, which is the closest living relative of humans, largely remains elusive. Therefore, the current study aims to characterize HML-9 in the chimpanzee genome and to compare the results with those in the human genome. Firstly, we report the distribution and genetic structural characterization of the 26 proviral elements and 38 solo LTR elements of HML-9 in the chimpanzee genome. The results showed that the distribution of these elements displayed a non-random integration pattern, and only six elements maintained a relatively complete structure. Then, we analyze their phylogeny and reveal that the identified elements all cluster together with HML-9 references and with those identified in the human genome. The HML-9 integration time was estimated based on the 2-LTR approach, and the results showed that HML-9 elements were integrated into the chimpanzee genome between 14 and 36 million years ago and into the human genome between 18 and 49 mya. In addition, conserved motifs, cis-regulatory regions, and enriched PBS sequence features in the chimpanzee genome were predicted based on bioinformatics. The results show that pathways significantly enriched for ERV LTR-regulated genes found in the chimpanzee genome are closely associated with disease development, including neurological and neurodevelopmental psychiatric disorders. In summary, the identification, characterization, and genomics of HML-9 presented here not only contribute to our understanding of the role of ERVs in primate evolution but also to our understanding of their biofunctional significance.

Role of FMRP in AKT/mTOR pathway-mediated hippocampal autophagy in fragile X syndrome.

Fragile X syndrome (FXS) is caused by epigenetic silencing of the Fmr1 gene, leading to the deletion of the coding protein FMRP. FXS induces abnormal hippocampal autophagy and mTOR overactivation. However, it remains unclear whether FMRP regulates hippocampal autophagy through the AKT/mTOR pathway, which influences the neural behavior of FXS. Our study revealed that FMRP deficiency increased the protein levels of p-ULK-1 and p62 and decreased LC3II/LC3I level in Fmr1 knockout (KO) mice. The mouse hippocampal neuronal cell line HT22 with knockdown of Fmr1 by lentivirus showed that the protein levels of p-ULK-1 and p62 were increased, whereas LC3II/LC3I was unchanged. Further observations revealed that FMRP deficiency obstructed autophagic flow in HT22 cells. Therefore, FMRP deficiency inhibited autophagy in the mouse hippocampus and HT22 cells. Moreover, FMRP deficiency increased reactive oxygen species (ROS) level, decreased the co-localization between the mitochondrial outer membrane proteins TOM20 and LC3 in HT22 cells, and caused a decrease in the mitochondrial autophagy protein PINK1 in HT22 cells and Fmr1 KO mice, indicating that FMRP deficiency caused mitochondrial autophagy disorder in HT22 cells and Fmr1 KO mice. To explore the mechanism by which FMRP deficiency inhibits autophagy, we examined the AKT/mTOR signaling pathway in the hippocampus of Fmr1 KO mice, found that FMRP deficiency caused overactivation of the AKT/mTOR pathway. Rapamycin-mediated mTOR inhibition activated and enhanced mitochondrial autophagy. Finally, we examined whether rapamycin affected the neurobehavior of Fmr1 KO mice. The Fmr1 KO mice exhibited stereotypical behavior, impaired social ability, and learning and memory impairment, while rapamycin treatment improved behavioral disorders in Fmr1 KO mice. Thus, our study revealed the molecular mechanism by which FMRP regulates autophagy function, clarifying the role of hippocampal neuron mitochondrial autophagy in the pathogenesis of FXS, and providing novel insights into potential therapeutic targets of FXS.