The role of axon guidance molecules in the pathogenesis of epilepsy.

Current treatments for epilepsy can only manage the symptoms of the condition but cannot alter the initial onset or halt the progression of the disease. Consequently, it is crucial to identify drugs that can target novel cellular and molecular mechanisms and mechanisms of action. Increasing evidence suggests that axon guidance molecules play a role in the structural and functional modifications of neural networks and that the dysregulation of these molecules is associated with epilepsy susceptibility. In this review, we discuss the essential role of axon guidance molecules in neuronal activity in patients with epilepsy as well as the impact of these molecules on synaptic plasticity and brain tissue remodeling. Furthermore, we examine the relationship between axon guidance molecules and neuroinflammation, as well as the structural changes in specific brain regions that contribute to the development of epilepsy. Ample evidence indicates that axon guidance molecules, including semaphorins and ephrins, play a fundamental role in guiding axon growth and the establishment of synaptic connections. Deviations in their expression or function can disrupt neuronal connections, ultimately leading to epileptic seizures. The remodeling of neural networks is a significant characteristic of epilepsy, with axon guidance molecules playing a role in the dynamic reorganization of neural circuits. This, in turn, affects synapse formation and elimination. Dysregulation of these molecules can upset the delicate balance between excitation and inhibition within a neural network, thereby increasing the risk of overexcitation and the development of epilepsy. Inflammatory signals can regulate the expression and function of axon guidance molecules, thus influencing axonal growth, axon orientation, and synaptic plasticity. The dysregulation of neuroinflammation can intensify neuronal dysfunction and contribute to the occurrence of epilepsy. This review delves into the mechanisms associated with the pathogenicity of axon guidance molecules in epilepsy, offering a valuable reference for the exploration of therapeutic targets and presenting a fresh perspective on treatment strategies for this condition.

The rheumatoid arthritis gut microbial biobank reveals core microbial species that associate and effect on host inflammation and autoimmune responses.

Gut microbiota dysbiosis has been implicated in rheumatoid arthritis (RA) and influences disease progression. Although molecular and culture-independent studies revealed RA patients harbored a core microbiome and had characteristic bacterial species, the lack of cultured bacterial strains had limited investigations on their functions. This study aimed to establish an RA-originated gut microbial biobank (RAGMB) that covers and further to correlates and validates core microbial species on clinically used and diagnostic inflammation and immune indices. We obtained 3200 bacterial isolates from fecal samples of 20 RA patients with seven improved and 11 traditional bacterial cultivation methods. These isolates were phylogenetically identified and selected for RAGMB. The RAGMB harbored 601 bacterial strains that represented 280 species (including 43 novel species) of seven bacterial phyla. The RAGMB covered 93.2% at species level of medium- and high-abundant (relative abundances ≥0.2%) RA gut microbes, and included four rare species of the phylum Synergistota. The RA core gut microbiome was defined and composed of 20 bacterial species. Among these, Mediterraneibacter tenuis and Eubacterium rectale were two species that statistically and significantly correlated with clinically used diagnostic indices such as erythrocyte sedimentation rate (ESR) and IL-10. Thus, M. tenuis and E. rectale were selected for experimental validation using DSS-treated and not DSS-treated mice model. Results demonstrated both M. tenuis and E. rectale exacerbated host inflammatory responses, including shortened colon length and increased spleen weight, decreased IL-10 and increased IL-17A levels in plasma. Overall, we established the RAGMB, defined the RA core microbiome, correlated and demonstrated core microbial species effected on host inflammatory and immune responses. This work provides diverse gut microbial resources for future studies on RA etiology and potential new targets for new biomedical practices.

The epigenetic modification of DNA methylation in neurological diseases.

Methylation, a key epigenetic modification, is essential for regulating gene expression and protein function without altering the DNA sequence, contributing to various biological processes, including gene transcription, embryonic development, and cellular functions. Methylation encompasses DNA methylation, RNA methylation and histone modification. Recent research indicates that DNA methylation is vital for establishing and maintaining normal brain functions by modulating the high-order structure of DNA. Alterations in the patterns of DNA methylation can exert significant impacts on both gene expression and cellular function, playing a role in the development of numerous diseases, such as neurological disorders, cardiovascular diseases as well as cancer. Our current understanding of the etiology of neurological diseases emphasizes a multifaceted process that includes neurodegenerative, neuroinflammatory, and neurovascular events. Epigenetic modifications, especially DNA methylation, are fundamental in the control of gene expression and are critical in the onset and progression of neurological disorders. Furthermore, we comprehensively overview the role and mechanism of DNA methylation in in various biological processes and gene regulation in neurological diseases. Understanding the mechanisms and dynamics of DNA methylation in neural development can provide valuable insights into human biology and potentially lead to novel therapies for various neurological diseases.

Sustainable ammonia and amines from chitin.

Efforts are underway to explore alternative methods to the Haber-Bosch process for sustainable ammonia production, while the potential for ammonia extraction from natural nitrogenous biomass is under-exploited. Here, a synergistic catalytic strategy involving acid and modified Ru-based catalysts is communicated for the direct production of amines and ammonia from chitin. Phosphoric acid promotes the cleavage of ether bonds in biomass polymers and also serves to protect amino groups from being removed. Selective hydrogenation, deoxygenation, and amination can be achieved by controllably adjusting the ratio of Ru0/Run+. The utilization of nitrogen atoms in chitin can reach up to 95 % (21 % amines, 74 % ammonium), and the catalytic process is applicable to waste shrimp shells. This study demonstrates the possibility of efficient production of nitrogen-containing compounds from abundant biopolymers.

Pathogenic Th17 cells are a potential therapeutic target for tacrolimus in AChR-myasthenia gravis patients.

In our study, we investigated the impact of tacrolimus (TAC) on CD4+ T cell subsets in 41 AChR-MG patients over 12 weeks. Twenty-seven patients were classified as the response group (RG) (improved myasthenia gravis composite scores ≥3), while 14 were non-response. We found that TAC treatment significantly reduced Th17 and pathogenic Th17 cells, along with IL-17 levels in RG, while Th1 and Tfh cells slightly decreased without affecting Th2 or Treg subsets. This indicates that TAC's clinical benefits may be due to its inhibitory effect on the Th17 response, enhancing our insight into its immunomodulatory mechanisms in MG management.

Development of a droplet digital PCR assay for the detection of BK polyomavirus.

The objective of this study was to establish a more sensitive and specific diagnostic method for detecting plasma BK polyomavirus (BKPyV) DNA load in patients after renal transplantation using droplet digital polymerase chain reaction (ddPCR) and to validate the methodology. The linear range, lower limit of detection, accuracy, precision, and specificity of the detection system were evaluated by using the WHO BKPyV standard (7.2 log10 IU/mL) as a reference, in accordance with the relevant documents of the Clinical and Laboratory Standards Institute. Plasma samples were collected from 74 renal transplantation patients with urinary BKPyV-DNA levels exceeding 7 log10 copies/mL. Quantitative PCR (qPCR) and ddPCR were performed, and their diagnostic efficacy for BKPyV-DNA in the diagnosis of BK polyomavirus-associated nephropathy was evaluated using a receiver operating characteristic (ROC) curve. The coefficients of variation for the repeated detection of BKPyV standard DNA were 2.55 and 4.71 at concentrations of 6.2 and 3.2 log10 IU/mL, respectively. The linear range was 2.2-6.2 log10 IU/mL, and the lowest detection limit was 100 IU/mL. By utilizing histopathological examination of renal biopsy as the gold standard for BKPyV diagnosis, the area under the ROC curve of 74 post-transplantation plasma samples detected by the ddPCR system was found to be 0.875 (95% CI: 0.797-0.953, P < 0.01). The optimal threshold was 512.86 copies/mL, with a sensitivity of 90.0% and a specificity of 67.6%. In comparison, the area under the ROC curve for qPCR was 0.668 (95% CI: 0.583-0.752, P < 0.01), with an optimal threshold of 11,481.54 copies/mL, a sensitivity of 35.0%, and a specificity of 100.0%. Pairwise comparison (Delong test) of the ROC curves of the two systems showed a significant difference in the area under the curve, with a difference of 0.207 and a P-value <0.01. The BKPyV nucleic acid detection system, based on ddPCR, is appropriate for the regular monitoring of the BK polyomavirus, specifically in plasma samples containing low viral DNA loads while it provides the benefits of both absolute quantification and high sensitivity.IMPORTANCEIt was previously believed that droplet digital polymerase chain reaction had limitations, including high cost, limited throughput, and cumbersome operation, which hindered its widespread application in clinical practice. However, the current fully automated digital PCR platform, combined with streamlined operations, can detect 96 samples at once, and the entire process can be completed within an hour, laying a solid foundation for its extensive use.

Kaposi's sarcoma-associated herpesvirus infection and its association with all-cause and cardiovascular mortality in the general adults: A prospective cohort study.

To investigate the association between Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8 (HHV8) infection and both all-cause and cardiovascular mortality in a representative cohort of US adults, data from the National Health and Nutrition Examination Survey III (NHANES III; 1988‒1994) were analyzed, including 13,993 participants aged 18‒90 years who underwent KSHV serology evaluations. Mortality outcomes were ascertained through December 2019 using the National Death Index. Cox proportional hazards models were employed to examine the association between KSHV seropositivity and mortality, adjusting for potential confounders such as age, sex, ethnicity, body mass index, and serum TG. Over a median follow-up period of 26.5 years, 5503 deaths were recorded. KSHV seropositivity was associated with an increased hazard of all-cause mortality (Hazard Ratio [HR]: 1.32, 95% Confidence Interval [CI]: 1.03‒1.69) and cardiovascular mortality (HR: 1.58, 95% CI: 1.00‒2.50) after adjusting for age, sex, ethnicity, and body mass index. Notably, the association between KSHV infection and all-cause mortality persisted among women (HR: 1.32, 95% CI: 1.02‒1.72) after adjusting for all confounders, whereas the association with cardiovascular mortality was only statistically significant for men (HR: 1.90, 95% CI: 1.02, 3.53).KSHV infection may represent an independent risk factor for all-cause and cardiovascular mortality among US adults. These findings highlight the need for further research to validate these associations in independent populations and to elucidate the biological mechanisms underlying the observed increased mortality associated with KSHV infection.

Two-Dimensional MoS2-Based Anisotropic Synaptic Transistor for Neuromorphic Computing by Localized Electron Beam Irradiation.

Neuromorphic computing, a promising solution to the von Neumann bottleneck, is paving the way for the development of next-generation computing and sensing systems. Axon-multisynapse systems enable the execution of sophisticated tasks, making them not only desirable but essential for future applications in this field. Anisotropic materials, which have different properties in different directions, are being used to create artificial synapses that can mimic the functions of biological axon-multisynapse systems. However, the restricted variety and unadjustable conductive ratio limit their applications. Here, it is shown that anisotropic artificial synapses can be achieved on isotropic materials with externally localized doping via electron beam irradiation (EBI) and purposefully induced trap sites. By employing the synapses along different directions, artificial neural networks (ANNs) are constructed to accomplish variable neuromorphic tasks with optimized performance. The localized doping method expands the axon-multisynapse device family, illustrating that this approach has tremendous potentials in next-generation computing and sensing systems.

Synthesis of Amphiphilic Polyacrylates as Peelable Coatings for Optical Surface Cleaning.

Optical instruments require extremely high precision, and even minor surface contamination can severely impact their performance. Peelable coatings offer an effective and non-damaging method for removing contaminants from optical surfaces. In this study, an amphiphilic polyacrylate copolymer (PMLEA) was synthesized via solution radical copolymerization using the lipophilic monomer lauryl acrylate (LA) and hydrophilic monomers ER-10, methyl methacrylate (MMA), and butyl acrylate (BA). The structure and molecular weight of the copolymer were characterized using Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and gel permeation chromatography (GPC). The hydrophilic-lipophilic balance, surface tension, and wettability of the copolymer were analyzed through water titration, the platinum plate method, and liquid contact angle tests. The cleaning performance of the copolymer coating on quartz glass surface contaminants was evaluated using optical microscopy and Ultraviolet-Visible Near-Infrared (UV-Vis-NIR) spectroscopy. The study examined the effect of varying the ratio of LA to ER-10 on the hydrophilicity, lipophilicity, cleaning efficiency, and mechanical properties of the copolymer coating. The results showed that when the mass ratio of LA to ER-10 was 1:2, the synthesized copolymer exhibited optimal performance in removing dust, grease, and fingerprints from quartz glass surfaces. The coating had a tensile strength of 2.57 MPa, an elongation at break of 183%, and a peeling force of 2.07 N m-1.

Epidemiological characteristics of influenza outbreaks in schools in Jiangsu Province, China, 2020-2023 post-COVID-19 pandemic.

BACKGROUND: This study aimed to analyze the epidemic characteristics and influencing factors of school influenza outbreaks in Jiangsu Province, China from 2020 to 2023,following the COVID-19 pandemic, to inform prevention and control strategies. METHODS: Data on influenza-like illness(ILI) outbreaks from the Chinese Influenza Surveillance Information System and national-level influenza surveillance sentinel hospitals were analyzed. The temporal distribution, school type, virus strains, and outbreak scales were examined using descriptive statistics. RESULTS: From 2020 to 2023, 1142 influenza outbreaks occurred in schools, with primary schools(ages 6 to 12) accounting for 71.80%. Most large outbreaks were caused by A(H1N1) and A(H3N2), responsible for 8.99% of total outbreaks. Outbreaks were predominantly reported in the pre-peak periods of B(Victoria) and A(H1N1) circulation, accounting for 86.31% and 92.32% of their respective total outbreaks. No concurrent influenza and COVID-19 outbreaks were observed during the study period. CONCLUSION: Primary and secondary schools are high-risk settings for influenza outbreaks. A(H3N2) shows higher adaptability and is more likely to co-circulate with other subtypes/lineages, especially A(H1N1), leading to larger outbreaks. B(Victoria)-caused outbreaks are more frequent but smaller in scale. School influenza outbreaks are more likely to occur during the early stages of seasonal peaks, particularly for B(Victoria) and A(H1N1). This suggests that influenza outbreaks in schools may play a crucial role in seeding and accelerating the spread of the virus within the broader community.

Enhanced protection and bioavailability of Lycium barbarum leaf extract through encapsulation in whey protein isolate and bovine serum albumin nanoparticles.

To improve the stability and bioavailabilityhe of polyphenolics in Lycium barbarum leaf, this study encapsulated L. barbarum leaf extracts (LLE) within whey protein isolate (WPI) and bovine serum albumin (BSA) nanoparticles (NPs) via self-assembly to enhance polyphenol distribution. The physicochemical properties of nanoparticles were characterized using transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and thermogravimetric (TG), respectively. The nanoparticles also showed good physical stability at various temperatures, different pH and NaCl concentrations. Compared with BSA-LLE NPs, WPI-LLE NPs exhibited strong physical stability with encapsulation efficiency of 70.6 %. The polyphenol nanoparticles demonstrated enhanced stability in the presence of stomach acid during in vitro simulated digestion. Additionally, the nanoparticles enhanced polyphenol stability during simulated gastrointestinal digestion. Following intestinal digestion, compared with LLE, the bioaccessibility of total phenolic increased by 53.67 % (WPI-LLE NPs), with specific enhancement in compounds like kaempferol, rutin, and chlorogenic acid.

Abalone shell-derived Mg-doped mesoporous hydroxyapatite microsphere drug delivery system loaded with icariin for inducing apoptosis of osteosarcoma cells.

Hydroxyapatite (HAP) porous microspheres with very high specific surface area and drug loading capacity, as well as excellent biocompatibility, have been widely used in tumour therapy. Mg2+ is considered to be a key factor in bone regeneration, acting as an active agent to stimulate bone and cartilage formation, and is effective in accelerating cell migration and promoting angiogenesis, which is essential for bone tissue repair, anti-cancer, and anti-infection. In this study, abalone shells from a variety of sources were used as raw materials, and Mg2+-doped abalone shell-derived mesoporous HAP microspheres (Mg-HAP) were prepared by hydrothermal synthesis as Mg2+/ icariin smart dual delivery system (ICA-Mg-HAP, IMHA). With increasing of Mg2+ doping, the surface morphology of HAP microspheres varied from collapsed macroporous to mesoporous to smooth and non-porous, which may be due to Mg2+ substitution or coordination in the HAP lattice. At 30% Mg2+ doping, the Mg-HAP microspheres showed a more homogeneous mesoporous morphology with a high specific surface area (186.06 m2/g). The IMHA microspheres showed high drug loading (7.69%) and encapsulation rate (83.29%), sustained Mg2+ release for more than 27 days, sustained and stable release of icariin for 60 hours, and good responsiveness to pH (pH 6.4 > pH 5.6). In addition, the IMHA delivery system stimulated the rapid proliferation of bone marrow mesenchymal stem cells and induced apoptosis in MG63 cells by blocking the G2 phase cycle of osteosarcoma cells and stimulating the high expression of apoptotic genes (Bcl-2, caspase-3, -8, -9). This suggests that the abalone shell-based IMHA may have potential applications in drug delivery and tumour therapy.

Low-field-driven large strain in lead zirconate titanium-based piezoceramics incorporating relaxor lead magnesium niobate for actuation.

Studies on the piezoelectric materials capable of efficiently outputting high electrostrains at low electric fields are driven by the demand for precise actuation in a wide range of applications. Large electrostrains of piezoceramics in operation require high driving fields, which limits their practical application due to undesirable nonlinearities and high energy consumption. Herein, a strategy is developed to enhance the electrostrains of piezoceramics while maintaining low hysteresis by incorporating lead magnesium niobate relaxors into lead zirconate titanium at the morphotropic phase boundary. An ultrahigh inverse piezoelectric coefficient d 33 * of 1380 pm/V with a reduced hysteresis of 11.5% is achieved under a low electric field of 1 kV/mm, outperforming the major lead-based piezoelectric materials. In situ synchrotron X-ray diffraction and domain wall dynamics characterization with sub-microsecond temporal resolution reveal that the outstanding performances originate from facilitated domain wall movement, which in turn is due to reduced lattice distortion and miniaturized domain structures. These findings not only address the pending challenges of effective actuation under reduced driving conditions but also lay the foundation for a more systematic approach to exploring the origin of large electrostrains.

Anti irradiation nanoparticles shelter immune organ from radio-damage via preventing the IKK/IκB/NF-κB activation.

BACKGROUND: Normal tissue and immune organ protection are critical parts of the tumor radiation therapy process. Radiation-induced immune organ damage (RIOD) causes several side reactions by increasing oxidative stress and inflammatory responses, resulting in unsatisfactory curability in tumor radiation therapy. The aim of this study was to develop a novel and efficient anti irradiation nanoparticle and explore its mechanism of protecting splenic tissue from radiation in mice. METHODS: Nanoparticles of triphenylphosphine cation NIT radicals (NPs-TPP-NIT) were prepared and used to protect the spleens of mice irradiated with X-rays. Splenic tissue histopathology and hematological parameters were investigated to evaluate the protective effect of NPs-TPP-NIT against X-ray radiation. Proteomics was used to identify differentially expressed proteins related to inflammatory factor regulation. In addition, in vitro and in vivo experiments were performed to assess the impact of NPs-TPP-NIT on radiation therapy. RESULTS: NPs-TPP-NIT increased superoxide dismutase, catalase, and glutathione peroxidase activity and decreased malondialdehyde levels and reactive oxygen species generation in the spleens of mice after exposure to 6.0 Gy X-ray radiation. Moreover, NPs-TPP-NIT inhibited cell apoptosis, blocked the activation of cleaved cysteine aspartic acid-specific protease/proteinase, upregulated the expression of Bcl-2, and downregulated that of Bax. We confirmed that NPs-TPP-NIT prevented the IKK/IκB/NF-κB activation induced by ionizing radiation, thereby alleviating radiation-induced splenic inflammatory damage. In addition, when used during radiotherapy for tumors in mice, NPs-TPP-NIT exhibited no significant toxicity and conferred no significant tumor protective effects. CONCLUSIONS: NPs-TPP-NIT prevented activation of IKK/IκB/NF-κB signaling, reduced secretion of pro-inflammatory factors, and promoted production of anti-inflammatory factors in the spleen, which exhibited radiation-induced damage repair capability without diminishing the therapeutic effect of radiation therapy. It suggests that NPs-TPP-NIT serve as a potential radioprotective drug to shelter immune organs from radiation-induced damage.

Tumor Microenvironment Cascade Activated Biodegradable Nano-Enzymes for Glutathione-Depletion and Ultrasound-Enhanced Chemodynamic Therapy.

Chemodynamic therapy (CDT) is emerged as a novel and promising tumor therapy by using the powerful reactive oxygen species (ROS) to kill cancer cells. However, the current CDT is remarkably inhibited due to insufficient H2O2 supply and over-expression of glutathione (GSH) in the tumor microenvironment (TME). Herein, a biodegradable self-supplying H2O2 nano-enzyme of CuO2@CaP with a GSH-consumption effect is designed for cascade enhanced CDT to overcome the problem of H2O2 deficiency and GSH overexpression. In this design, CuO2@CaP is gradually degraded to Ca2+, Cu2+, and H2O2 in acidic TME, resulting in synergistically enhanced CDT owing to the efficient self-supplied H2O2 and GSH-depletion and Ca2+ overload therapy. Interestingly, the faster degradation of CuO2@CaP and promoted production rate of •OH are further achieved after triggering with ultrasound (US). And, the US-enhanced CDT and Ca2+ overload synergistic antitumor therapy is successfully achieved in vivo. These findings provide a promising strategy for designing biodegradable nano-enzymes with self-supplying H2O2 and GSH consumption for US-mediated CDT.

Spatiotemporal cerebral blood flow dynamics underlies emergence of the limbic-sensorimotor-association cortical gradient in human infancy.

Infant cerebral blood flow (CBF) delivers nutrients and oxygen to fulfill brain energy consumption requirements for the fastest period of postnatal brain development across the lifespan. However, organizing principle of whole-brain CBF dynamics during infancy remains obscure. Leveraging a unique cohort of 100+ infants with high-resolution arterial spin labeled MRI, we find the emergence of the cortical hierarchy revealed by the highest-resolution infant CBF maps available to date. Infant CBF across cortical regions increases in a biphasic pattern featured by initial rapid and subsequently slower rate, and break-point ages increasing along the limbic-sensorimotor-association cortical gradient. Increases in CBF in sensorimotor cortices are associated with enhanced language and motor skills, and frontoparietal association cortices with cognitive skills. The study discovers emergence of the hierarchical limbic-sensorimotor-association cortical gradient in infancy and offers standardized reference of infant brain CBF and insight into the physiological basis of cortical specialization and real-world infant developmental functioning.

Phytochemical constituents from root barks of Eleutherococcus henryi Oliv. and their anti-neuroinflammatory effect.

ETHNOPHARMACOLOGICAL RELEVANCE: The cortex of Eleutherococcus henryi (EH, Araliaceae), also known as "Wu-Jia-Pi", is known for its effects such as dispelling wind and dampness, calming the mind and enhancing intelligence, removing heat and toxin, strengthening muscles and bones, and nourishing the liver and kidneys. Throughout Chinese history and tradition, it has been used for conditions like amnesia, mental fatigue, arthritis, hepatitis, and rheumatism. However, research evaluating its neuroprotective effects and pharmacological properties remains scarce. AIM OF THE STUDY: The goal is to explore the anti-neuroinflammatory properties of EH in vitro and to discover precisely the bioactive natural products within the medicinal plant that are relevant to its traditional usage. MATERIALS AND METHODS: Utilizing chromatographic techniques, a phytochemical exploration was conducted. The phytochemical structures of the natural products were then elucidated through an analysis involving comprehensive spectra and a comparison with relevant data from published studies. Network pharmacology combined with molecular dynamics simulations (MDs) and docking were applied to forecast potential anti-neuroinflammatory targets of active compounds. In vitro, the anti-neuroinflammatory efficacy was evaluated via the suppression of inflammatory mediators activated by lipopolysaccharide (LPS) in BV2 microglia. RESULTS: The methanol extract of E.henryi (EHME) restrained the NO release in LPS-activated BV2 microglia, demonstrating anti-neuroinflammatory activity. Subsequently, chemical composition analysis revealed the separation and elucidation of 31 secondary metabolites, comprising 7 new compounds (1-7) and 1 new natural product (8). Based on LPS-induced BV2 cell in vitro activity tests, compounds 4-17, 19, 20, 22, 23, 26, 29 and 31 were found to exhibit potential anti-neuroinflammatory activity, with compound 6 showing the highest efficacy. Furthermore, employing network pharmacology in conjunction with both molecular docking and MDs, potential anti-neuroinflammatory targets of compound 6 were predicted to include TLR4, Src, MAPK, and NF-κB. Finally, validation through in vitro experiments confirmed that the anti-neuroinflammatory mechanism of compound 6 is associated with the TLR4/Src/MAPK p38/NF-κB p65 signaling pathways. CONCLUSIONS: The study affirmed the traditional efficacy of E. henryi and unveiled novel lignans as potent agents against neuroinflammation.

Ultra-processed food consumption and renal cell carcinoma incidence and mortality: results from a large prospective cohort.

BACKGROUND: Growing evidence shows that ultra-processed food consumption is associated with the risk of cancer. However, prospective evidence is limited on renal cell carcinoma (RCC) incidence and mortality. In this study, we aimed to examine the association of ultra-processed food consumption and RCC incidence and mortality in a large cohort of US adults. METHODS: A population-based cohort of 101,688 participants were included from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Ultra-processed food items were confirmed by using the NOVA food classification system. The consumption of ultra-processed food was expressed as a percentage of total food intake (g/day). Prospective associations were calculated using Cox regression. Restricted cubic spline regression was used to assess nonlinearity. Subgroup analyses were performed to investigate the potential effect modifiers on the incidence and mortality of RCC. RESULTS: A total of 410 participants developed RCC during a total of 899,731 person-years of follow-up (median 9.41 years) and 230 RCC deaths during 1,533,930 person-years of follow-up (median 16.85 years). In the fully adjusted model, participants in the highest compared with the lowest quintiles of ultra-processed food consumption had a higher risk of RCC (HR quartile 4 vs 1:1.42; 95% CI: 1.06-1.91; Ptrend = 0.004) and mortality (HR quartile 4 vs. quartile 1: 1.64; 95% CI: 1.10-2.43; Ptrend = 0.027). Linear dose-response associations with RCC incidence and mortality were observed for ultra-processed food consumption (all Pnonlinearity > 0.05). The reliability of these results was supported by sensitivity and subgroup analyses. CONCLUSION: In conclusion, higher consumption of ultra-processed food is associated with an increased risk of RCC incidence and mortality. Limiting ultra-processed food consumption might be a primary prevention method of RCC.

Investigating mechanisms of Sophora davidii (Franch.) skeels flower extract in treating LPS-induced acute pneumonia based on network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: In TCM opinion, most of pneumonia is related to "lung heat". Sophora davidii (Franch.) Skeels flower was first documented in "Guizhou Herbal Medicine", and was recorded as having functions of clearing heat, detoxifying, and cooling blood. It can be used to treat lung heat cough. AIM OF THE STUDY: To investigate main mechanisms of Sophora davidii flower extract (SDFE) in Treating LPS-induced acute Pneumonia. MATERIALS AND METHODS: Acute pneumonia models on BEAS-2B cells and rats were established using LPS. The rat model was used to verified the protective effects of SDFE through HE staining, lung tissue W/D ratio assay, white blood cell count analysis, and ammonia-induced coughing test. Network pharmacology was applied to predict the active compounds, core targets and main pathways of SDFE in treating acute pneumonia. Western Blot and ELISA kits were employed to validate representative proteins in selected pathway in vivo and in vitro. RESULTS: HE staining, lung tissue W/D ratio assay, white blood cell count analysis, and ammonia-induced coughing test showed SDFE could improve pathological features (leukocyte infiltration, pulmonary edema, lung injury and cough). Network pharmacology indicated MAPK/NF-κB pathway was the most relevant pathway. SDFE could significantly inhibit the expression of Fos and Jun, and the phosphorylation levels of p38, ERK, JNK, NF-κB and IκB. It also down-regulated the expression of pro-inflammatory factors (TNF-α, IL-6 and IL-1ß). CONCLUSIONS: SDFE can exert protective effects against acute pneumonia through the MAPK/NF-κB signaling pathway.

Wireless, Programmable, and Refillable Hydrogel Bioelectronics for Enhanced Diabetic Wound Healing.

Diabetic wounds, characterized by complex pathogenesis and high infection rates, pose significant challenges in treatment due to prolonged recovery times and high recurrence rates, often leading to severe complications such as amputation and death. Traditional dry dressing treatments fail to address the unique microenvironment of diabetic wounds and tend to cause secondary damage due to frequent replacement. In this study, an electronic-embedding, drug-loading hydrogel bioelectronics is reported for accelerating diabetic wound healing using a combination of programmable pharmaceutical and electrostimulative approaches. Encapsulated in stretchable and biocompatible materials, this device is capable of multiple drug refilling and accelerated drug release modulated by on-board electronics. In vivo experiments on diabetic model rats confirm the device's effectiveness in promoting wound healing. This innovative approach implies the potential for improving diabetic wound management using a combination of physical, material, and pharmaceutical interventions.