Study on plasma metabolomics profiling of depression in Chinese community-dwelling older adults based on untargeted LC/GC‒MS.

Depression is a serious psychiatric illness that causes great inconvenience to the lives of elderly individuals. However, the diagnosis of depression is somewhat subjective. Nontargeted gas chromatography (GC)/liquid chromatography (LC)-mass spectrometry (MS) was used to study the plasma metabolic profile and identify objective markers for depression and metabolic pathway variation. We recruited 379 Chinese community-dwelling individuals aged ≥ 65. Plasma samples were collected and detected by GC/LC‒MS. Orthogonal partial least squares discriminant analysis and a heatmap were utilized to distinguish the metabolites. Receiver operating characteristic curves were constructed to evaluate the diagnostic value of these differential metabolites. Additionally, metabolic pathway enrichment was performed to reveal metabolic pathway variation. According to our standard, 49 people were included in the depression cohort (DC), and 49 people age- and sex-matched individuals were included in the non-depression cohort (NDC). 64 metabolites identified via GC‒MS and 73 metabolites identified via LC‒MS had significant contributions to the differentiation between the DC and NDC, with VIP values > 1 and p values < 0.05. Three substances were detected by both methods: hypoxanthine, phytosphingosine, and xanthine. Furthermore, 1-(sn-glycero-3-phospho)-1D-myo-inositol had the largest area under the curve (AUC) value (AUC = 0.842). The purine metabolic pathway is the most important change in metabolic pathways. These findings show that there were differences in plasma metabolites between the depression cohort and the non-depression cohort. These identified differential metabolites may be markers of depression and can be used to study the changes in depression metabolic pathways.

The composition and function of bacterial communities in Bombyx mori (Lepidoptera: Bombycidae) changed dramatically with infected fungi: A new potential to culture Cordyceps cicadae.

Cordyceps cicadae (Hypocreales: Cordycipitaceae) is a renowned entomopathogenic fungus used as herbal medicine in China. However, wild C. cicadae resources have been threatened by heavy harvesting. We hypothesised that Bombyx mori L. (Lepidoptera: Bombycidae) could be a new alternative to cultivate C. cicadae due to the low cost of rearing. Bacterial communities are crucial for the formation of Cordyceps and for promoting the production of metabolites. To better understand the bacterial community structure associated with Cordyceps, three Claviciptaceae fungi were used to explore the pathogenicity of the silkworms. Here, fifth-instar silkworms were infected with C. cicadae, Cordyceps cateniannulata (Hypocreales: Cordycipitaceae) and Beauveria bassiana (Hypocreales: Cordycipitaceae). Subsequently, we applied high-throughput sequencing to explore the composition of bacterial communities in silkworms. Our results showed that all three fungi were highly pathogenic to silkworms, which suggests that silkworms have the potential to cultivate Cordyceps. After fungal infection, the diversity of bacterial communities in silkworms decreased significantly, and the abundance of Staphylococcus increased in mummified larvae, which may play a role in the death process when the host suffers infection by entomopathogenic fungi. Furthermore, there were high similarities in the bacterial community composition and function in the C. cicadae and C. cateniannulata infected samples, and the phylogenetic analysis suggested that these similarities may be related to the fungal phylogenetic relationship. Our findings reveal that infection with different entomopathogenic fungi affects the composition and function of bacterial communities in silkworms and that the bacterial species associated with Cordyceps are primarily host dependent, while fungal infection affects bacterial abundance.

DNA methylation of skeletal muscle function-related secretary factors identifies FGF2 as a potential biomarker for sarcopenia.

BACKGROUND: Sarcopenia is characterized by progressive loss of muscle mass and function due to aging. DNA methylation has been identified to play important roles in the dysfunction of skeletal muscle. The aim of our present study was to explore the whole blood sample-based methylation changes of skeletal muscle function-related factors in patients with sarcopenia. METHODS: The overall DNA methylation levels were analysed by using MethlTarget™ DNA Methylation Analysis platform in a discovery set consistent of 50 sarcopenic older adults (aged ≥65 years) and 50 age- and sex-matched non-sarcopenic individuals. The candidate differentially methylated regions (DMRs) were further validated by Methylation-specific PCR (MSP) in another two independent larger sets and confirmed by pyrosequencing. Receiver operating characteristic (ROC) curve analysis was used to determine the optimum cut-off levels of fibroblast growth factor 2 (FGF2)_30 methylation best predicting sarcopenia and area under the ROC curve (AUC) was measured. The correlation between candidate DMRs and the risk of sarcopenia was investigated by univariate analysis and multivariate logistic regression analysis. RESULTS: Among 1149 cytosine-phosphate-guanine (CpG) sites of 27 skeletal muscle function-related secretary factors, 17 differentially methylated CpG sites and 7 differentially methylated regions (DMRs) were detected between patients with sarcopenia and control subjects in the discovery set. Further methylation-specific PCR identified that methylation of fibroblast growth factor 2 (FGF2)_30 was lower in patients with sarcopenia and the level was decreased as the severity of sarcopenia increased, which was confirmed by pyrosequencing. Correlation analysis demonstrated that the methylation level of FGF2_30 was positively correlated to ASMI (r = 0.372, P < 0.001), grip strength (r = 0.334, P < 0.001), and gait speed (r = 0.411, P < 0.001). ROC curve analysis indicated that the optimal cut-off value of FGF2_30 methylation level that predicted sarcopenia was 0.15 with a sensitivity of 84.6% and a specificity of 70.1% (AUC = 0.807, 95% CI = 0.756-0.858, P < 0.001). Multivariate logistic regression analyses showed that lower FGF2_30 methylation level (<0.15) was significantly associated with increased risk of sarcopenia even after adjustment for potential confounders including age, sex, and BMI (adjusted OR = 9.223, 95% CI: 6.614-12.861, P < 0.001). CONCLUSIONS: Our results suggest that lower FGF2_30 methylation is correlated with the risk and severity of sarcopenia in the older adults, indicating that FGF2 methylation serve as a surrogate biomarker for the screening and evaluation of sarcopenia.

Functional Analysis of the GhIQD1 Gene in Cotton Resistance to Verticillium Wilt.

Cotton is a critical crop with massive economic implications worldwide. Verticillium wilt is a soil-borne ailment caused by Verticillium dahliae, which harms the growth and development of cotton. Therefore, investigating the genes associated with resistance to verticillium wilt is of particular significance. In this study, we identified the GhIQD1 gene through transcriptome analysis and experimentally characterized the role of the GhIQD1 gene in cotton against V. dahliae. The findings indicated that GhIQD1 acts as a calmodulin-binding protein. The expression of GhIQD1 was the highest in stems, and the expression level increased significantly following infection with V. dahliae. The expression in resistant cotton varieties was higher than in susceptible cotton varieties. Through overexpression of the GhIQD1 gene in tobacco, these transgenic plants exhibited improved resistance to V. dahliae. In contrast, by silencing the GhIQD1 gene in cotton through VIGS, the resistance to V. dahliae was reduced. Following inoculation, the leaves yellowed, and the disease index was higher. Transcriptome analysis of transgenic tobacco 72 h after inoculation indicated that overexpression of GhIQD1 increased the enrichment of the calmodulin pathway and stimulated the production of plant hormones alongside secondary metabolites. Consequently, we investigated the relationship between the GhIQD1 gene and plant disease-resistant hormones SA, JA, and ABA. In summary, this study uncovered the mechanism by which GhIQD1 conferred resistance to V. dahliae in cotton through positive regulation of JA and ABA, providing crucial information for further research on the adaptation of plants to pathogen invasion.

Endovascular treatment of direct carotid cavernous fistula resulting from rupture of intracavernous carotid aneurysm: A case report.

BACKGROUND: Direct carotid cavernous fistulas (CCFs) are typically the result of a severe traumatic brain injury. High-flow arteriovenous shunts secondary to rupture of an intracavernous aneurysm, resulting in direct CCFs, are rare. The use of a pipeline embolization device in conjunction with coils and Onyx glue for treatment of direct high-flow CCF resulting from ruptured cavernous carotid artery aneurysm in a clinical setting is not well documented. CASE SUMMARY: A 58-year-old woman presented to our department with symptoms of blepharoptosis and intracranial bruits for 1 wk. During physical examination, there was right eye exophthalmos and ocular motor palsy. The rest of the neurological examination was clear. Notably, the patient had no history of head injury. The patient was treated with a pipeline embolization device in the ipsilateral internal carotid artery across the fistula. Coils and Onyx were placed through the femoral venous route, followed by placement of the pipeline embolization device with assistance from a balloon-coiling technique. No intraoperative or perioperative complications occurred. Preoperative symptoms of bulbar hyperemia and bruits subsided immediately after the operation. CONCLUSION: Pipeline embolization device in conjunction with coiling and Onyx may be a safe and effective approach for direct CCFs.

Phillygenin Alleviates Arthritis through the Inhibition of the NLRP3 Inflammasome and Ferroptosis by AMPK.

We investigated the potential arthritis-inducing effects of Phillygenin and its underlying mechanisms. RAW264.7 cells were stimulated with lipopolysaccharide to induce inflammation. Phillygenin was found to reduce arthritis score, histopathological changes, paw edema, spleen index, and ALP levels in a dose-dependent manner in a model of arthritis. Additionally, Phillygenin was able to decrease levels of inflammation markers in serum samples of mice with arthritis and also inhibited inflammation markers in the cell supernatant of an in vitro model of arthritis. Phillygenin increased cell viability and JC-1 disaggregation, enhanced calcien-AM/CoCl2, reduced LDH activity levels and IL-1a levels, and inhibited Calcein/PI levels and iron concentration in an in vitro model. Phillygenin was also found to reduce ROS-induced oxidative stress and Ferroptosis, and suppress the NLRP3 inflammasome in both in vivo and in vitro models through AMPK. In the in vivo model, Phillygenin was observed to interact with AMPK protein. These findings suggest that Phillygenin may be a potential therapeutic target for preventing arthritis by inhibiting NLRP3 inflammasome and Ferroptosis through AMPK. This indicates that Phillygenin could have disease-modifying effects on arthritis.

Giant In-Plane Flexoelectricity and Radial Polarization in Janus IV-VI Monolayers and Nanotubes.

Nanotubes have established a new paradigm in nanoscience because of their atomically thin geometries and intriguing properties. However, because of their typical metastability compared to their 2D and 3D counterparts, it is still fundamentally challenging to synthesize nanotubes with controlled size. New strategies have been suggested for synthesizing nanotubes with a controlled geometry. One of these is considering Janus 2D layers, which can self-roll to form a nanotube. Herein, we study 412 nanotubes (along the armchair and zigzag directions) based on 36 Janus IV-VI compounds using density functional theory (DFT) calculations. By investigating the energy-radius relationship using structural models and Bayesian predictions, the most stable nanotubes show negative strain energies and radii below 20 Å, where curvature effects can play a significant role. The band structures show that the selected nanotubes exhibit sizable band gaps and size-dependent electronic properties. More strikingly, the flexoelectricity along the in-plane directions and radial directions in these nanotubes is significantly larger than that in other nanotubes and their 2D counterparts. This work opens up an avenue of structure-property relationships of Janus IV-VI nanotubes and demonstrates giant flexoelectricity in these nanotubes for future electronic and energy applications.

Using 3D Printing Technology to Design Split-Piece Sleeve Prosthesis in the Revision Surgery of Tumor-Type Total Elbow Prosthetic Fractures: A Case Report.

BACKGROUND: Revision of tumor-type prosthetic fractures is very challenging in clinical work. Traditional repair methods may not be able to meet the needs of complex cases or cause greater bone damage. Therefore, more effective and reliable solutions need to be found. CASE PRESENTATION: This study presents a novel revision technique for managing fractures of tumor-type total elbow prostheses. A 57-year-old female patient was diagnosed with a left distal humeral bone tumor accompanied by pathological fracture and underwent customized tumor-type total elbow prosthesis arthroplasty. After 5 years, she experienced pain and encountered difficulty in flexing the left elbow while lifting heavy objects. The X-ray examination revealed a fracture of the distal humeral prosthesis. As a response, the elbow joint was initially explored, and the damaged component of the prosthesis was extracted. Subsequently, we utilized 3D printing technology to design a split-piece sleeve prosthesis and effectively restored the fractured left distal humerus implant. During the 2-year follow-up, The X-ray demonstrated satisfactory positioning of the prosthesis, which remained securely affixed without any indications of loosening. The Mayo Elbow Performance Score (MEPS) reached 80 points, the Musculoskeletal Tumor Society (MSTS) attained a score of 28 points, and the range of motion of the elbow was measured between 25° and 110°, revealing favorable functional outcomes. CONCLUSION: The utilization of a 3D printed split-piece sleeve prosthesis presents a viable clinical treatment strategy for addressing fractures in tumor-type elbow prostheses.

Nitrogen Doping-Roused Synergistic Active Sites in Perovskite Enabling Highly Selective CO2 Photoreduction into CH4.

The intricate protonation process in carbon dioxide reduction usually makes the product unpredictable. Thus, it is significant to control the reactive intermediates to manipulate the reaction steps. Here, we propose that the synergistic La-Ti active sites in the N-La2Ti2O7 nanosheets enable the highly selective carbon dioxide photoreduction into methane. In the photoreduction of CO2 over N-La2Ti2O7 nanosheets, in situ Fourier transform infrared spectra are utilized to monitor the *CH3O intermediate, pivotal for methane production, whereas such monitoring is not conducted for La2Ti2O7 nanosheets. Also, theoretical calculations testify to the increased charge densities on the Ti and La atoms and the regulated formation energy barrier of *CO and *CH3O intermediates by the constructed synergistic active sites. Accordingly, the methane formation rate of 7.97 µL h-1 exhibited by the N-La2Ti2O7 nanosheets, along with an electron selectivity of 96.6%, exceeds that of most previously reported catalysts under similar conditions.

Breaking the Activity-Selectivity Trade-off for CH4-to-C2H6 Photoconversion.

Photocatalytic conversion of methane (CH4) to ethane (C2H6) has attracted extensive attention from academia and industry. Typically, the traditional oxidative coupling of CH4 (OCM) reaches a high C2H6 productivity, yet the inevitable overoxidation limits the target product selectivity. Although the traditional nonoxidative coupling of CH4 (NOCM) can improve the product selectivity, it still encounters unsatisfied activity, arising from being thermodynamically unfavorable. To break the activity-selectivity trade-off, we propose a conceptually new mechanism of H2O2-triggered CH4 coupling, where the H2O2-derived ·OH radicals are rapidly consumed for activating CH4 into ·CH3 radicals exothermically, which bypasses the endothermic steps of the direct CH4 activation by photoholes and the interaction between ·CH3 and ·OH radicals, affirmed by in situ characterization techniques, femtosecond transient absorption spectroscopy, and density-functional theory calculation. By this pathway, the designed Au-WO3 nanosheets achieve unprecedented C2H6 productivity of 76.3 mol molAu-1 h-1 with 95.2% selectivity, and TON of 1542.7 (TOF = 77.1 h-1) in a self-designed flow reactor, outperforming previously reported photocatalysts regardless of OCM and NOCM pathways. Also, under outdoor natural sunlight irradiation, the Au-WO3 nanosheets exhibit similar activity and selectivity toward C2H6 production, showing the possibility for practical applications. Interestingly, this strategy can be applied to other various photocatalysts (Au-WO3, Au-TiO2, Au-CeO2, Pd-WO3, and Ag-WO3), showing a certain universality. It is expected that the proposed mechanism adds another layer to our understanding of CH4-to-C2H6 conversion.

Uridine diphosphate glucosyltransferase is vital for fenpropathrin resistance in Bombyx mori (Lepidoptera).

The silkworm (Bombyx mori) is an important model lepidopteran insect and can be used to identify pesticide resistance-related genes of great significance for biological control of pests. Uridine diphosphate glucosyltransferases (UGTs), found in all organisms, are the main secondary enzymes involved in the metabolism of heterologous substances. However, it remains uncertain if silkworm resistance to fenpropathrin involves UGT. This study observes significant variations in BmUGT expression among B. mori strains with variable fenpropathrin resistance post-feeding, indicating BmUGT's role in fenpropathrin detoxification. Knockdown of BmUGT with RNA interference and overexpression of BmUGT significantly decreased and increased BmN cell activity, respectively, indicating that BmUGT plays an important role in the resistance of silkworms to fenpropathrin. In addition, fenpropathrin residues were significantly reduced after incubation for 12 h with different concentrations of a recombinant BmUGT fusion protein. Finally, we verified the conservation of UGT to detoxify fenpropathrin in Spodoptera exigua: Its resistance to fenpropathrin decreased significantly after knocking down SeUGT. In a word, UGT plays an important role in silkworm resistance to fenpropathrin by directly degrading the compound, a function seen across other insects. The results of this study are of great significance for breeding silkworm varieties with high resistance and for biological control of pests.

Metabolic Heterogeneity and Potential Immunotherapeutic Responses Revealed by Single-Cell Transcriptomics of Breast Cancer.

BACKGROUND: Breast cancer (BC) exhibits remarkable heterogeneity. However, the transcriptomic heterogeneity of BC at the single-cell level has not been fully elucidated. METHODS: We acquired BC samples from 14 patients. Single-cell RNA sequencing (scRNA-seq), bioinformatic analyses, along with immunohistochemistry (IHC) and immunofluorescence (IF) assays were carried out. RESULTS: According to the scRNA-seq results, 10 different cell types were identified. We found that Cancer-Associated Fibroblasts (CAFs) exhibited distinct biological functions and may promote resistance to therapy. Metabolic analysis of tumor cells revealed heterogeneity in glycolysis, gluconeogenesis, and fatty acid synthetase reprogramming, which led to chemotherapy resistance. Furthermore, patients with multiple metastases and progression were predicted to benefit from immunotherapy based on a heterogeneity analysis of T cells and tumor cells. CONCLUSIONS: Our findings provide a comprehensive understanding of the heterogeneity of BC, provide comprehensive insight into the correlation between cancer metabolism and chemotherapy resistance, and enable the prediction of immunotherapy responses based on T-cell heterogeneity.

Preparation of Ti3C2Tx modified rare earth doped PbO2 electrodes for efficient removal of sulfamethoxazole.

In this study, we deposited Ti3C2Tx-modified, rare-earth-doped PbO2 on the surface of a carbon fabric via electrodeposition. The surface morphology and electronic structure of the electrode were characterized with SEM, XRD and XPS. The layered Ti3C2Tx did not change the structure of ß-PbO2, and at the same time, it improved the crystallinity of the material and reduced the grains of PbO2. Electrochemical experiments showed that the addition of Ti3C2Tx increased the electrochemical activity of the electrode and produced more H2O2, which contributed to the degradation of pollutants. The efficiency of sulfamethoxazole (SMX) degradation reached 95% after 120 min at pH 3 with a current density of 50 mA/cm2. Moreover, the electrode has good cycling performance, and the degradation efficiency was still 80% after 120 min after 10 cycles of recycling. Based on the intermediates identified by HPLC‒MS, a mechanism for SMX degradation was proposed. Our results will provide a new idea for the development of efficient electrocatalytic degradation of antibiotics.

Fabrication of 3D-Printed Hydrocortisone Triple Pulsatile Tablet Using Fused Deposition Modelling Technology.

Hydrocortisone (HC) is the optimal drug for adolescents diagnosed with congenital adrenal hyperplasia (CAH). Because traditional dosage regimens HC are inconvenient, our study used fused deposition modeling (FDM) three-dimensional (3D) printing technology to solve the problems caused by traditional preparations. First, we designed a core-shell structure tablet with an inner instant release component and an outer delayed release shell. The instant release component was Kollicoat IR: glycerol (GLY): HC = 76.5:13.5:10. Then, we used Affinisol® HPMC 15LV to realize delayed release. Furthermore, we investigated the relationship between the thickness of the delayed release shell and the delayed release time, and an equation was derived through binomial regression analysis. Based on that equation, a novel triple pulsatile tablet with an innovative structure was devised. The tablet was divided into three components, and the drug was released multiple times at different times. The dose and release rate of the tablets can be adjusted by modifying the infill rate of the printing model. The results indicated that the triple pulsatile tablet exhibited desirable release behavior in vitro. Moreover, the physicochemical properties of the drug, excipients, filaments, and tablets were characterized. All these results indicate that the FDM 3D printing method is a convenient technique for producing preparations with intricate structures.

Effect of resveratrol on herpesvirus encephalitis: Evidences for its mechanisms of action.

BACKGROUND: Herpes simplex virus type 1 (HSV-1)-induced herpes simplex encephalitis (HSE) has a high mortality rate in clinically immunocompromised patients, while recovered patients often experience neurological sequelae due to neuroinflammation. Nucleoside drugs and nucleoside analogues such as acyclovir and ganciclovir are mainly used in clinical treatment, and the emergence of resistant viral strains makes the development of new anti-herpesvirus encephalitis drugs urgent. Resveratrol is a multifunctional, plant-derived bioactive compound and its antiviral potential is attracting much attention. PURPOSE: This study aimed to investigate the anti-HSV-1 mechanism of resveratrol in microglial cells and in the HSE mouse model. METHODS: The antiviral effect of resveratrol on HSV-1 infection was investigated by plaque assay, virus titer, immunofluorescence, Western blot and time-of-addition assay. The influence of resveratrol on stimulator of interferon gene (STING)/Nuclear Factor kappa B (NF-κB) signaling pathway-mediated neuroinflammation was examined by Western blot, RT-qPCR and ELISA. The interaction between resveratrol and STING/heat shock protein 90 beta (HSP90ß) was evaluated by molecular modeling, co-immunoprecipitation, and drug affinity responsive target stability assay. The therapeutic effect of resveratrol on HSE was evaluated in the HSE mouse model by analyzing weight loss, neurodegenerative symptoms and histopathological scores. RESULTS: Resveratrol inhibited the early process of HSV-1 infection, and interfered with the STING/NF-κB signaling pathway to attenuate HSV-1-induced neuroinflammation and microglial M1 polarization, independent of its classical target Sirtuin1. Mechanistically, resveratrol completely bound to Glu515 and Lys491 of HSP90ß, thus disrupting the HSP90ß-STING interaction and promoting STING degradation. Resveratrol also significantly alleviated viral encephalitis and neuroinflammation caused by HSV-1 in the HSE mouse model. CONCLUSION: Resveratrol acted as a non-classical HSP90ß inhibitor, binding to the STING-HSP90ß interaction site to promote STING degradation and attenuate HSV-1-induced encephalitis and neuroinflammation. These findings suggest the alternative strategy of targeting HSP90ß and resveratrol-mediated inhibition of HSP90ß as a potential antiviral approach.

Bombyx mori voltage-dependent anion-selective channel induces programmed cell death to defend against Bombyx mori nucleopolyhedrovirus infection.

BACKGROUND: Voltage-dependent anion-selective channels (VDACs) serve as pore proteins within the mitochondrial membrane, aiding in the regulation of cell life and cell death. Although the occurrence of cell death is crucial for defense against virus infection, the function played by VDAC in Bombyx mori, in response to the influence of Bombyx mori nucleopolyhedrovirus (BmNPV), remains unclear. RESULTS: BmVDAC was found to be relatively highly expressed both during embryonic development, and in the Malpighian tubule and midgut. Additionally, the expression levels of BmVDAC were found to be different among silkworm strains with varying levels of resistance to BmNPV, strongly suggesting a connection between BmVDAC and virus infection. To gain further insight into the function of BmVDAC in BmNPV, we employed RNA interference (RNAi) to silence and overexpress it by pIZT/V5-His-mCherry. The results revealed that BmVDAC is instrumental in developing the resistance of host cells to BmNPV infection in BmN cell-line cells, which was further validated as likely to be associated with initiating programmed cell death (PCD). Furthermore, we evaluated the function of BmVDAC in another insect, Spodoptera exigua. Knockdown of the BmVDAC homolog in S. exigua, SeVDAC, made the larvae more sensitive to BmNPV. CONCLUSION: We have substantiated the pivotal role of BmVDAC in conferring resistance against BmNPV infection, primarily associated with the initiation of PCD. The findings of this study shine new light on the molecular mechanisms governing the silkworm's response to BmNPV infection, thereby supporting innovative approaches for pest biocontrol. © 2024 Society of Chemical Industry.

Resolving neuroinflammatory and social deficits in ASD model mice: Dexmedetomidine downregulates NF-κB/IL-6 pathway via α2AR.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that severely affects individuals' daily life and social development. Unfortunately, there are currently no effective treatments for ASD. Dexmedetomidine (DEX) is a selective agonist of α2 adrenergic receptor (α2AR) and is widely used as a first-line medication for sedation and hypnosis in clinical practice. In recent years, there have been reports suggesting its potential positive effects on improving emotional and cognitive functions. However, whether dexmedetomidine has therapeutic effects on the core symptoms of ASD, namely social deficits and repetitive behaviors, remains to be investigated. In the present study, we employed various behavioral tests to assess the phenotypes of animals, including the three-chamber, self-grooming, marble burying, open field, and elevated plus maze. Additionally, electrophysiological recordings, western blotting, qPCR were mainly used to investigate and validate the potential mechanisms underlying the role of dexmedetomidine. We found that intraperitoneal injection of dexmedetomidine in ASD model mice-BTBR T+ Itpr3tf/J (BTBR) mice could adaptively improve their social deficits. Further, we observed a significant reduction in c-Fos positive signals and interleukin-6 (IL-6) expression level in the prelimbic cortex (PrL) of the BTBR mice treated with dexmedetomidine. Enhancing or inhibiting the action of IL-6 directly affects the social behavior of BTBR mice. Mechanistically, we have found that NF-κB p65 is a key pathway regulating IL-6 expression in the PrL region. In addition, we have confirmed that the α2AR acts as a receptor switch mediating the beneficial effects of dexmedetomidine in improving social deficits. This study provides the first evidence of the beneficial effects of dexmedetomidine on core symptoms of ASD and offers a theoretical basis and potential therapeutic approach for the clinical treatment of ASD.

pH-Triggered Controlled Release of Chlorhexidine Using Chitosan-Coated Titanium Silica Composite for Dental Infection Prevention.

Peri-implantitis is a growing pathological concern for dental implants which aggravates the occurrence of revision surgeries. This increases the burden on both hospitals and the patients themselves. Research is now focused on the development of materials and accompanying implants designed to resist biofilm formation. To enhance this endeavor, a smart method of biofilm inhibition coupled with limiting toxicity to the host cells is crucial. Therefore, this research aims to establish a proof-of-concept for the pH-triggered release of chlorhexidine (CHX), an antiseptic commonly used in mouth rinses, from a titanium (Ti) substrate to inhibit biofilm formation on its surface. To this end, a macroporous Ti matrix is filled with mesoporous silica (together referred to as Ti/SiO2), which acts as a diffusion barrier for CHX from the CHX feed side to the release side. To limit release to acidic conditions, the release side of Ti/SiO2 is coated with crosslinked chitosan (CS), a pH-responsive and antimicrobial natural polymer. Scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM/EDX) and Fourier transform infrared (FTIR) spectroscopy confirmed successful CS film formation and crosslinking on the Ti/SiO2 disks. The presence of the CS coating reduced CHX release by 33% as compared to non-coated Ti/SiO2 disks, thus reducing the antiseptic exposure to the environment in normal conditions. Simultaneous differential scanning calorimetry and thermogravimetric analyzer (SDT) results highlighted the thermal stability of the crosslinked CS films. Quartz crystal microbalance with dissipation monitoring (QCM-D) indicated a clear pH response for crosslinked CS coatings in an acidic medium. This pH response also influenced CHX release through a Ti/SiO2/CS disk where the CHX release was higher than the average trend in the neutral medium. Finally, the antimicrobial study revealed a significant reduction in biofilm formation for the CS-coated samples compared to the control sample using viability quantitative polymerase chain reaction (v-qPCR) measurements, which were also corroborated using SEM imaging. Overall, this study investigates the smart triggered release of pharmaceutical agents aimed at inhibiting biofilm formation, with potential applicability to implant-like structures.

Association of urinary chlorpyrifos, paraquat, and cyproconazole levels with the severity of fatty liver based on MRI.

BACKGROUND: The objective of this study was to detect the urinary levels of chlorpyrifos, paraquat, and cyproconazole in residents living in Fuyang City and to analyze the correlation between these urinary pesticides levels and the severity of fatty liver disease (FLD). METHODS: All participants' fat fraction (FF) values were recorded by MRI (Magnetic resonance imaging). First-morning urine samples were collected from 53 participants from Fuyang Peoples'Hospital. The levels of three urinary pesticides were measured using ß-glucuronidase hydrolysis followed by a. The results were analyzed by using Pearson correlation analysis and binary logistic regression analysis to reveal the correlation between three urinary pesticides and the severity of fatty liver. RESULTS: 53 individuals were divided into 3 groups based on the results from MRI, with 20 cases in the normal control group, 16 cases in the mild fatty liver group, and 17 cases in the moderate and severe fatty liver group. Urinary chlorpyrifos level was increased along with the increase of the severity of fatty liver. Urinary paraquat level was significantly higher both in the low-grade fatty liver group and moderate & serve grade fatty liver group compared with the control group. No significant differences in urinary cyproconazole levels were observed among the three groups. Furthermore, urinary chlorpyrifos and paraquat levels were positively correlated with FF value. And chlorpyrifos was the risk factor that may be involved in the development of FLD and Receiver Operating Characteristic curve (ROC curve) analysis showed that chlorpyrifos and paraquat may serve as potential predictors of FLD. CONCLUSION: The present findings indicate urinary chlorpyrifos and paraquat were positively correlated with the severity of fatty liver. Moreover, urinary chlorpyrifos and paraquat have the potential to be considered as the predictors for development of FLD. Thus, this study may provide a new perspective from the environmental factors for the diagnosis, prevention, and treatment of FLD.