Quantitative Proteomics Reveals the Relationship between Protein Changes and Volatile Flavor Formation in Hunan Bacon during Low-Temperature Smoking.

This study aimed to investigate the changes in proteins and volatile flavor compounds that occur in bacon during low-temperature smoking (LTS) and identify potential correlations between these changes. To achieve this, a combination of gas chromatography-mass spectrometry and proteomics was employed. A total of 42 volatile flavor compounds were identified in the bacon samples, and, during LTS, 11 key volatile flavor compounds with variable importance were found at a projection value of >1, including 2',4'-dihydroxyacetophenone, 4-methyl-2H-furan-5-one, Nonanal, etc. In total, 2017 proteins were quantified at different stages of LTS; correlation coefficients and KEGG analyses identified 27 down-regulated flavor-related proteins. Of these, seven were involved in the tricarboxylic acid (TCA) cycle, metabolic pathways, or amino acid metabolism, and they may be associated with the process of flavor formation. Furthermore, correlation coefficient analysis indicated that certain chemical parameters, such as the contents of free amino acids, carbonyl compounds, and TCA cycle components, were closely and positively correlated with the formation of key volatile flavor compounds. Combined with bioinformatic analysis, the results of this study provide insights into the proteins present in bacon at various stages of LTS. This study demonstrates the changes in proteins and the formation of volatile flavor compounds in bacon during LTS, along with their potential correlations, providing a theoretical basis for the development of green processing methods for Hunan bacon.

Mechanisms of the Masquelet technique to promote bone defect repair and its influencing factors.

The Masquelet technique, also known as the induced membrane technique, is a surgical technique for repairing large bone defects based on the use of a membrane generated by a foreign body reaction for bone grafting. This technique is not only simple to perform, with few complications and quick recovery, but also has excellent clinical results. To better understand the mechanisms by which this technique promotes bone defect repair and the factors that require special attention in practice, we examined and summarized the relevant research advances in this technique by searching, reading, and analysing the literature. Literature show that the Masquelet technique may promote the repair of bone defects through the physical septum and molecular barrier, vascular network, enrichment of mesenchymal stem cells, and high expression of bone-related growth factors, and the repair process is affected by the properties of spacers, the timing of bone graft, mechanical environment, intramembrane filling materials, artificial membrane, and pharmaceutical/biological agents/physical stimulation.

The effect of forest-based health and wellness on the stress-relieve of middle-aged people.

In order to explore the impact of experience in forest-based health and wellness (FHW) on the stress of middle-aged people, 12 participants aged 35-39 were selected to conduct a 3-day/2-night study on FHW experience in Wencheng, Wenzhou. Huawei bracelets were used to monitor participants' movement, pulse and blood pressure and their mood state was measured before and after the health care experience using the Profile of Mood States (POMS) scale. After the FHW experience, the lowest value of bracelet stress appeared on the second day of the experience for men and women. The total mood disturbance (TMD) decreased by 38.8 points on average, which significantly improved the positive mood and relieved the stress. The decompression effect of the FHW experience showed some variability among individuals. Furthermore, there were gender differences in alleviation of fatigue and puzzlement, which was greater for females than males.

A comparative analysis of TCR immune repertoire in COVID-19 patients.

The coronavirus disease 2019 (COVID-19) has merged as a global health threat since its outbreak in December 2019. Despite widespread recognition, there has been a paucity of studies focusing on the T cell receptor (TCR) bias in adaptive immunity induced by SARS-CoV-2. This research conducted a comparative analysis of the TCR immune repertoire to identify notable αß TCR bias sequences associated with the SARS-CoV-2 virus antigen. The present study encompassed 73 symptomatic COVID-19 patients, categorized as moderate/mild or severe/critical, along with 9 healthy controls. Our findings revealed specific TCR chains prominently utilized by moderate and severe patients, identified as TRAV30-J34-TRBV3-1-J2-7 and TRAV12-3-J6-TRBV28-J1-1, respectively. Additionally, our research explored critical TCR preferences in the bronchoalveolar lavage fluid (BALF) of COVID-19 patients at various disease stages. Indeed, monitoring the dynamics of immune repertoire changes in COVID-19 patients could serve as a crucial biomarker for predicting disease progression and recovery. Furthermore, the study explored TCR bias in both peripheral blood mononuclear cells (PBMCs) and BALF. The most common αß VJ pair observed in BALF was TRAV12-3-J18-TRBV7-6-J2-7. In addition, a comparative analysis with the VDJdb database indicated that the HLA-A*02:01 allele exhibited the widest distribution and highest frequency in COVID-19 patients across different periods. This comprehensive examination provided a global characterization of the TCR immune repertoire in COVID-19 patients, contributing significantly to our understanding of TCR bias induced by SARS-CoV-2.

Leaky gut, circulating immune complexes, arthralgia, and arthritis in IBD: coincidence or inevitability?

Most host-microbiota interactions occur within the intestinal barrier, which is essential for separating the intestinal epithelium from toxins, microorganisms, and antigens in the gut lumen. Gut inflammation allows pathogenic bacteria to enter the blood stream, forming immune complexes which may deposit on organs. Despite increased circulating immune complexes (CICs) in patients with inflammatory bowel disease (IBD) and discussions among IBD experts regarding their potential pathogenic role in extra-intestinal manifestations, this phenomenon is overlooked because definitive evidence demonstrating CIC-induced extra-intestinal manifestations in IBD animal models is lacking. However, clinical observations of elevated CICs in newly diagnosed, untreated patients with IBD have reignited research into their potential pathogenic implications. Musculoskeletal symptoms are the most prevalent extra-intestinal IBD manifestations. CICs are pivotal in various arthritis forms, including reactive, rheumatoid, and Lyme arthritis and systemic lupus erythematosus. Research indicates that intestinal barrier restoration during the pre-phase of arthritis could inhibit arthritis development. In the absence of animal models supporting extra-intestinal IBD manifestations, this paper aims to comprehensively explore the relationship between CICs and arthritis onset via a multifaceted analysis to offer a fresh perspective for further investigation and provide novel insights into the interplay between CICs and arthritis development in IBD.

Comprehensive Review of EGCG Modification: Esterification Methods and Their Impacts on Biological Activities.

Epigallocatechin gallate (EGCG), the key constituent of tea polyphenols, presents challenges in terms of its lipid solubility, stability, and bioavailability because of its polyhydroxy structure. Consequently, structural modifications are imperative to enhance its efficacy. This paper comprehensively reviews the esterification techniques applied to EGCG over the past two decades and their impacts on bioactivities. Both chemical and enzymatic esterification methods involve catalysts, solvents, and hydrophobic groups as critical factors. Although the chemical method is cost-efficient, it poses challenges in purification; on the other hand, the enzymatic approach offers improved selectivity and simplified purification processes. The biological functions of EGCG are inevitably influenced by the structural changes incurred through esterification. The antioxidant capacity of EGCG derivatives can be compromised under certain conditions by reducing hydroxyl groups, while enhancing lipid solubility and stability can strengthen their antiviral, antibacterial, and anticancer properties. Additionally, esterification broadens the utility of EGCG in food applications. This review provides critical insights into developing cost-effective and environmentally sustainable selective esterification methods, as well as emphasizes the elucidation of the bioactive mechanisms of EGCG derivatives to facilitate their widespread adoption in food processing, healthcare products, and pharmaceuticals.

Potential anti-hyperglycemic activity of black tea theaflavins through inhibiting α-amylase.

Hyperglycemia can cause early damage to human bady and develop into diabates that will severely threaten human healthy. The effectively clinical treatment of hyperglycemiais is by inhibiting the activity of α-amylase. Black tea has been reported to show inhibitory effect on α-amylase and can be used for hyperglycemia treatment. However, the mechanism underlying is unclear. In this study, in vivo experiment showed that black tea theaflavins extract (BTE) effectively alleviated hyperglycemia. In vitro experiment showed that the effects may be caused by the interation between theaflavins and α-amylase. While TF1 and TF3 were mixed type inhibitors of α-amylase, TF2A and TF2B were competitive inhibitors of α-amylase. Molecular docking analysis showed that theaflavins monomers interacted with the hydrophobic region of α-amylase. Further study verified that monomer-α-amylase complex was spontaneously formed depending on hydrophobic interactions. Taken together, theaflavins showed potential anti-hyperglycemia effect via inhibiting α-amylase activity. Our results suggested that theaflavins might be utilized as a new type of α-amylase inhibitor to prevent and cure hyperglycemia.

Glycyrrhizic acid treatment ameliorates anxiety-like behaviour via GLT1 and Per1/2-dependent pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: As a traditional Chinese medicinal herb, Glycyrrhiza. URALENSIS: Fisch. (licorice root, chinese name: Gancao) has a variety of medicinal values and is widely used clinically. Its main active ingredient, glycyrrhizic acid (GA), is believed to have a neuroprotective effect. However, the underlying biological mechanisms of GA on stress-induced anxiety disorders are still unclear. AIM OF THE STUDY: To investigate the anti-anxiety effect of GA and its underlying mechanism. METHODS: We selected the anxiety model induced by repeated chronic restraint stress (CRS) for 2 h on each of 7 consecutive days. GA (4, 20, 100 mg/kg) was injected intraperitoneally once daily for 1 week. The potential GA receptors were identified using whole-cell patches and computer-assisted docking of molecules. High-throughput RNA sequencing, adeno-associated virus-mediated gene regulation, Western blotting, and RT-qPCR were used to assess the underlying molecular pathways. RESULTS: GA alleviate depression-like and anxiety-like behaviors in CRS mice. GA decreased synaptic transmission by facilitating glutamate reuptaking in mPFC. Meanwhile, long-term GA treatment increased the expression of clock genes Per1 and Per2. Suppressing both Per1 and Per2 abolished the anxiolytic effects of GA treatment. CONCLUSION: Our study suggests that GA may be developed for the treatment of stress-induced anxiety disorders, and its mechanism is related to GLT1 and Per1/2-dependent pathways. This presents a novel approach to discovering potent therapeutic drugs.

Causal role of myeloid cells in Parkinson's disease: Mendelian randomization study.

BACKGROUND: Previous studies have observed elevated myeloid cells in the peripheral blood of patients with Parkinson's disease (PD), but the causal relationship between them remains to be elucidated. We investigated whether there is a causal relationship between different subtypes of peripheral blood myeloid cells and PD using Mendelian randomization (MR) combined with bioinformatics analysis. Exploring the etiology of PD from the perspective of genetics can remove confounding factors and provide a more reliable theoretical basis for elucidating the pathogenesis of PD. METHODS: Comprehensive two-sample MR analysis and sensitivity analyses were conducted to explore the causal associations between 64 myeloid cell signatures and PD risk. The Venn diagram and protein-protein interaction network analysis of instrumental variables (IV) corresponding genes were used to further investigate the potential mechanism of myeloid cells influencing the pathogenesis of PD. RESULTS: We investigated the impact of four immunophenotypes on the risk of PD, including Im MDSC% CD33dim HLA DR- CD66b- (relative count), CD33dim HLA DR+ CD11b+% CD33dim HLA DR+ (relative count), and CD11b on Mo MDSC (MFI) and CD11b on CD33br HLA DR+ CD14dim (MFI), while an immunophenotype's protective effect on PD was observed CD45 on Im MDSC (MFI). The results of bioinformatics analysis showed that CD33, NTRK2, PLD2, GRIK2 and RELN had protein interactions with the risk genes of PD. CONCLUSIONS: Our study has demonstrated a close genetic correlation between different subtypes of myeloid cells and PD, providing guidance for early identification and immunotherapeutic development in patients with PD.

Akkermansia muciniphila Is Beneficial to a Mouse Model of Parkinson's Disease, via Alleviated Neuroinflammation and Promoted Neurogenesis, with Involvement of SCFAs.

Increasing evidence suggests that the gut microbiota may represent potential strategies for Parkinson's disease (PD) treatment. Our previous research revealed a decreased abundance of Akkermansia muciniphila (Akk) in PD mice; however, whether Akk is beneficial to PD is unknown. To answer this question, the mice received MPTP intraperitoneally to construct a subacute model of PD and were then supplemented with Akk orally for 21 consecutive days. Motor function, dopaminergic neurons, neuroinflammation, and neurogenesis were examined. In addition, intestinal inflammation, and serum and fecal short-chain fatty acids (SCFAs) analyses, were assessed. We found that Akk treatment effectively inhibited the reduction of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and partially improved the motor function in PD mice. Additionally, Akk markedly alleviated neuroinflammation in the striatum and hippocampus and promoted hippocampal neurogenesis. It also decreased the level of colon inflammation. Furthermore, these aforementioned changes are mainly accompanied by alterations in serum and fecal isovaleric acid levels, and lower intestinal permeability. Our research strongly suggests that Akk is a potential neuroprotective agent for PD therapy.

Fingolimod improves diffuse brain injury by promoting AQP4 polarization and functional recovery of the glymphatic system.

BACKGROUND: Diffuse brain injury (DBI) models are characterized by intense global brain inflammation and edema, which characterize the most severe form of TBI. In a previous experiment, we found that fingolimod promoted recovery after controlled cortical impact injury (CCI) by modulating inflammation around brain lesions. However, it remains unclear whether fingolimod can also attenuate DBI because of its different injury mechanisms. Furthermore, whether fingolimod has additional underlying effects on repairing DBI is unknown. METHODS: The impact acceleration model of DBI was established in adult Sprague-Dawley rats. Fingolimod (0.5 mg/kg) was administered 0.5, 24, and 48 h after injury for 3 consecutive days. Immunohistochemistry, immunofluorescence analysis, cytokine array, and western blotting were used to evaluate inflammatory cells, inflammatory factors, AQP4 polarization, apoptosis in brain cells, and the accumulation of APP after DBI in rats. To evaluate the function of the glymphatic system (GS), a fluorescent tracer was injected into the cistern. The neural function of rats with DBI was evaluated using various tests, including the modified neurological severity score (mNSS), horizontal ladder-crossing test, beam walking test, and tape sensing and removal test. Brain water content was also measured. RESULTS: Fingolimod administration for 3 consecutive days could reduce the levels of inflammatory cytokines, neutrophil recruitment, microglia, and astrocyte activation in the brain following DBI. Moreover, fingolimod reduced apoptotic protein expression, brain cell apoptosis, brain edema, and APP accumulation. Additionally, fingolimod inhibited the loss of AQP4 polarization, improved lymphatic system function, and reduced damage to nervous system function. Notably, inhibiting the GS weakened the therapeutic effect of fingolimod on the neurological function of rats with DBI and increased the accumulation of APP in the brain. CONCLUSIONS: In brief, these findings suggest that fingolimod alleviates whole-brain inflammation and GS system damage after DBI and that inhibiting the GS could weaken the positive effect of fingolimod on nerve function in rats with DBI. Thus, inhibiting inflammation and regulating the GS may be critical for the therapeutic effect of fingolimod on DBI.

Elucidation of the mechanism of action of ailanthone in the treatment of colorectal cancer: integration of network pharmacology, bioinformatics analysis and experimental validation.

Background: Ailanthone, a small compound derived from the bark of Ailanthus altissima (Mill.) Swingle, has several anti-tumour properties. However, the activity and mechanism of ailanthone in colorectal cancer (CRC) remain to be investigated. This study aims to comprehensively investigate the mechanism of ailanthone in the treatment of CRC by employing a combination of network pharmacology, bioinformatics analysis, and molecular biological technique. Methods: The druggability of ailanthone was examined, and its targets were identified using relevant databases. The RNA sequencing data of individuals with CRC obtained from the Cancer Genome Atlas (TCGA) database were analyzed. Utilizing the R programming language, an in-depth investigation of differentially expressed genes was carried out, and the potential target of ailanthone for anti-CRC was found. Through the integration of protein-protein interaction (PPI) network analysis, GO and KEGG enrichment studies to search for the key pathway of the action of Ailanthone. Then, by employing molecular docking verification, flow cytometry, Transwell assays, and Immunofluorescence to corroborate these discoveries. Results: Data regarding pharmacokinetic parameters and 137 target genes for ailanthone were obtained. Leveraging The Cancer Genome Atlas database, information regarding 2,551 differentially expressed genes was extracted. Subsequent analyses, encompassing protein-protein interaction network analysis, survival analysis, functional enrichment analysis, and molecular docking verification, revealed the PI3K/AKT signaling pathway as pivotal mediators of ailanthone against CRC. Additionally, the in vitro experiments indicated that ailanthone substantially affects the cell cycle, induces apoptosis in CRC cells (HCT116 and SW620 cells), and impedes the migration and invasion capabilities of these cells. Immunofluorescence staining showed that ailanthone significantly inhibited the phosphorylation of AKT protein and suppressed the activation of the PI3K/AKT signaling pathway, thereby inhibiting the proliferation and metastasis of CRC cells. Conclusion: Therefore, our findings indicate that Ailanthone exerts anti-CRC effects primarily by inhibiting the activation of the PI3K/AKT pathway. Additionally, we propose that Ailanthone holds potential as a therapeutic agent for the treatment of human CRC.

Novel hollow core-shell Zn0.5Cd0.5S@ZnIn2S4/MoS2 nanocages with Z-scheme heterojunction for enhanced photocatalysis of hydrogen generation.

The development of low-cost and efficient metal sulfide photocatalysts through morphological and structural design is vital to the advancement of the hydrogen economy. However, metal sulfide semiconductor photocatalysts still suffer from low carrier separation and poor solar-to-hydrogen conversion efficiencies. Herein, two-dimensional ZnIn2S4 nanosheets were grown on Zn0.5Cd0.5S hollow nanocages to construct Zn0.5Cd0.5S@ZnIn2S4 hollow nanocages for the first time. Novel hollow core-shell Zn0.5Cd0.5S@ZnIn2S4/MoS2 nanocages with Z-scheme heterojunction structures were obtained by incorporating MoS2 nanosheet co-catalyst via the solvothermal method. The resulting Zn0.5Cd0.5S@ZnIn2S4/MoS2 exhibited unique structural and compositional advantages, leading to remarkable photocatalytic hydrogen evolution rates of up to 8.5 mmol·h-1·g-1 without the use of any precious metal co-catalysts. This rate was 10.6-fold and 7.1-fold higher compared to pure ZnIn2S4 and Zn0.5Cd0.5S, respectively. Moreover, the optimized Zn0.5Cd0.5S@ZnIn2S4/MoS2 photocatalyst outperformed numerous reported ZnIn2S4-based photocatalysts and some ZnIn2S4-based photocatalysts based on precious metal co-catalysts. The exceptional photocatalytic performance of Zn0.5Cd0.5S@ZnIn2S4/MoS2 can be attributed to the Z-scheme heterojunction of core-shell structure that enhanced charge carrier separation and transport, as well as the co-catalytic action of MoS2. Overall, the proposed Zn0.5Cd0.5S@ZnIn2S4/MoS2 with heterojunction structure is a promising candidate for the preparation of efficient photocatalysts for solar-to-hydrogen energy conversion.

Exploring the causal relationship between B lymphocytes and Parkinson's disease: a bidirectional, two-sample Mendelian randomization study.

Parkinson's disease (PD) is a neurodegenerative disorder with extensive involvement of motor symptoms, imposing a heavy economic burden on patients and society. B lymphocytes, a group of immune cells associated with humoral immunity, have been shown to be involved in the pathogenesis of PD. However, the causal relationship and potential pathogenic effects of B cell in PD remain unclear. Based on the three core hypotheses of the Mendelian randomization (MR) study, we explored causal associations between 190 B-cell immunological traits and 482,730 European individuals (Ncase = 33,674, Ncontrol = 449,056) from genome wide association studies by means of the two-sample bidirectional MR method. The inverse­variance weighted method was selected as the main approach when conducting MR analysis. Finally, the results were verified by the heterogeneity and horizontal pleiotropy analyses. Five B-cell immunological phenotypes were nominally associated with PD at the significance threshold of P < 0.05. Concretely, IgD + CD38- B cell %lymphocyte (OR 1.052, 95% CI 1.001-1.106, P = 0.046), CD20 on IgD- CD24- B cell (OR 1.060, 95% CI 1.005-1.117, P = 0.032), CD38 on IgD+ CD24- B cell (OR 1.113, 95% CI 1.028-1.206, P = 0.009), and BAFF-R on CD20- B cell (OR 1.093, 95% CI 1.010-1.184, P = 0.027) were identified as risk factors for PD. Instead, CD38 on Plasma Blast-Plasma Cell (OR 0.894, 95% CI 0.802-0.996, P = 0.043) was proved to be protective. However, there is no statistically significant correlation between B cell and PD after Bonferroni correction. The results of reverse MR were negative, avoiding the reverse causal effects. Eventually, the association results were identified as stable across several sensitivity analyses. Briefly, our study might demonstrate the key factor of B cells in PD. Further studies are warranted to clarify the associations for early identification and immunotherapeutic development in PD patients.

Follicle stimulating hormone controls granulosa cell glutamine synthesis to regulate ovulation.

Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility. Inadequate understanding of the ovulation drivers hinders PCOS intervention. Herein, we report that follicle stimulating hormone (FSH) controls follicular fluid (FF) glutamine levels to determine ovulation. Murine ovulation starts from FF-exposing granulosa cell (GC) apoptosis. FF glutamine, which decreases in pre-ovulation porcine FF, elevates in PCOS patients FF. High-glutamine chow to elevate FF glutamine inhibits mouse GC apoptosis and induces hormonal, metabolic, and morphologic PCOS traits. Mechanistically, follicle-development-driving FSH promotes GC glutamine synthesis to elevate FF glutamine, which maintain follicle wall integrity by inhibiting GC apoptosis through inactivating ASK1-JNK apoptotic pathway. FSH and glutamine inhibit rapture of cultured murine follicles. Glutamine removal or ASK1-JNK pathway activation with metformin or AT-101 reversed PCOS traits in PCOS models that are induced with either glutamine or EsR1-KO. These suggest that glutamine, FSH and ASK1-JNK pathway are targetable to alleviate PCOS.

Multimodality management for chronic subdural hematoma in China: protocol and characteristics of an ambidirectional, nationwide, multicenter registry study.

BACKGROUND: Despite its prevalence, there is ongoing debate regarding the optimal management strategy for chronic subdural hematoma (CSDH), reflecting the variability in clinical presentation and treatment outcomes. This ambidirectional, nationwide, multicenter registry study aims to assess the efficacy and safety of multimodality treatment approaches for CSDH in the Chinese population. METHODS/DESIGN: A multicenter cohort of CSDH patients from 59 participating hospitals in mainland China was enrolled in this study. The treatment modalities encompassed a range of options and baseline demographics, clinical characteristics, radiographic findings, and surgical techniques were documented. Clinical outcomes, including hematoma resolution, recurrence rates, neurological status, and complications, were assessed at regular intervals during treatment, 3 months, 6 months, 1 year, and 2 years follow-up. RESULT: Between March 2022 and August 2023, a comprehensive cohort comprising 2173 individuals who met the criterion was assembled across 59 participating clinical sites. Of those patients, 81.1% were male, exhibiting an average age of 70.12 ± 14.53 years. A historical record of trauma was documented in 48.0% of cases, while headache constituted the predominant clinical presentation in 58.1% of patients. The foremost surgical modality employed was the burr hole (61.3%), with conservative management accounting for 25.6% of cases. Notably, a favorable clinical prognosis was observed in 88.9% of CSDH patients at 3 months, and the recurrence rate was found to be 2.4%. CONCLUSION: This registry study provides critical insights into the multimodality treatment of CSDH in China, offering a foundation for advancing clinical practices, optimizing patient management, and ultimately, improving the quality of life for individuals suffering from this challenging neurosurgical condition. TRIAL REGISTRATION: ChiCTR2200057179.

Inactivation of ERK1/2 signaling mediates dysfunction of basal meningeal lymphatic vessels in experimental subdural hematoma.

Rationale: Meningeal lymphatic vessels (MLVs) are essential for the clearance of subdural hematoma (SDH). However, SDH impairs their drainage function, and the pathogenesis remains unclear. Herein, we aimed to understand the pathological mechanisms of MLV dysfunction following SDH and to test whether atorvastatin, an effective drug for SDH clearance, improves meningeal lymphatic drainage (MLD). Methods: We induced SDH models in rats by injecting autologous blood into the subdural space and evaluated MLD using Gadopentetate D, Evans blue, and CFSE-labeled erythrocytes. Whole-mount immunofluorescence and transmission electron microscopy were utilized to detect the morphology of MLVs. Phosphoproteomics, western blot, flow cytometry, and in vitro experiments were performed to investigate the molecular mechanisms underlying dysfunctional MLVs. Results: The basal MLVs were detected to have abundant valves and play an important role in draining subdural substances. Following SDH, these basal MLVs exhibited disrupted endothelial junctions and dilated lumen, leading to impaired MLD. Subsequent proteomics analysis of the meninges detected numerous dephosphorylated proteins, primarily enriched in the adherens junction, including significant dephosphorylation of ERK1/2 within the meningeal lymphatic endothelial cells (LECs). Subdural injection of the ERK1/2 kinase inhibitor PD98059 resulted in dilated basal MLVs and impaired MLD, resembling the dysfunctional MLVs observed in SDH. Moreover, inhibiting ERK1/2 signaling severely disrupted intercellular junctions between cultured LECs. Finally, atorvastatin was revealed to protect the structure of basal MLVs and accelerate MLD following SDH. However, these beneficial effects of atorvastatin were abolished when combined with PD98059. Conclusion: Our findings demonstrate that SDH induces ERK1/2 dephosphorylation in meningeal LECs, leading to disrupted basal MLVs and impaired MLD. Additionally, we reveal a beneficial effect of atorvastatin in improving MLD.

Laryngopharyngeal Reflux and Benign Vocal Fold Lesions: A Systematic Review and Meta-analysis.

OBJECTIVE: There is a link between laryngopharyngeal reflux (LPR) and the formation of benign vocal fold lesions (BVFLs). However, previous studies have mainly focused on LPR suggested by symptoms and signs, rather than objectively diagnosed LPR via pharyngeal pH monitoring. We, therefore, conducted a Meta-analysis to evaluate the association between pharyngeal pH monitoring diagnosed LPR and the odds of BVFLs. DATA SOURCES: Relevant observational studies were identified by searching PubMed, Embase, Cochrane Library, and Web of Science. REVIEW METHODS: We evaluated between-study heterogeneity using the Cochrane Q test and estimated the I2 statistic. Random-effects models were used when significant heterogeneity was observed; otherwise, fixed-effects models were used. RESULTS: Thirteen datasets from 9 studies were included. Among them, 493 were diagnosed with LPR and 344 had BVFLs. LPR was related to a higher odds of BVFLs (odds ratio: 3.26, 95% confidence interval: 1.84-5.76, P < .001) with moderate heterogeneity (P for Cochrane Q test = .006, I2 = 57%). Subgroup analyses showed that the association was similar in studies with only pharyngeal pH monitoring (Restech), with double-probe or 3-site pH monitoring, and with 24-hour multichannel intraluminal impedance-pH monitoring (P for subgroup difference = .15). In addition, subgroup analysis showed consistent results in studies from Asia and Europe (P for subgroup analysis = .12), and the association seemed to be consistent for vocal Reinke's edema, nodules, and polyps (P for subgroup difference = .09). CONCLUSION: Pharyngeal pH monitoring diagnosed LPR is associated with the formation of BVFLs.

Investigating the TLR4/TAK1/IRF7 axis in NLRP3-Mediated Pyroptosis in Parkinson's Disease.

In the realm of Parkinson's disease (PD) research, NLRP3 inflammasome-mediated pyroptosis has recently garnered significant attention as a potential novel form of dopaminergic neuronal death. Our previous research revealed the activation of innate immune-related genes, such as the TLR4 signaling pathway and interferon regulatory factor 7 (IRF7), although the specific mechanism remains unclear. Our current study shed light on whether the TLR4 signaling pathway and IRF7 can affect the pyroptosis of dopaminergic nerve cells and thus participate in the pathogenesis of PD. The PD model was constructed by MPP+ treatment of PC12 cells or stereotactic injection of the striatum of SD rats, and the expression of genes were detected by RT-qPCR and Western Blotting. Lentivirus, siRNA and (5Z)-7-Oxozeaenol were used to validate the regulation of this pathway on pyroptosis. The expression of TLR4, TAK1, IRF7 and pyroptosis molecular markers was upregulated after MPP+ treatment. IRF7 could affect dopaminergic neural cells pyroptosis by targeted regulation of NLRP3. Furthermore, inhibition of the TLR4/TAK1 signaling pathway led to a decrease in the expression of both IRF7 and NLRP3, while overexpression of IRF7 reversed the reduction in pyroptosis and increase in TH expression. TLR4/TAK1/IRF7 axis can promote PD by influencing pyroptosis through NLRP3.

Manifestations and Outcomes of Intracerebral Hemorrhage During the COVID-19 Pandemic in China: Multicenter, Longitudinal Cohort Study.

BACKGROUND: The COVID-19 pandemic has inevitably affected the distribution of medical resources, and epidemic lockdowns have had a significant impact on the nursing and treatment of patients with other acute diseases, including intracerebral hemorrhage (ICH). OBJECTIVE: This study aimed to investigate how the COVID-19 pandemic affected the manifestations and outcomes of patients with ICH. METHODS: Patients with acute ICH before (December 1, 2018-November 30, 2019) and during (December 1, 2019-November 30, 2020) the COVID-19 pandemic at 31 centers in China from the Chinese Cerebral Hemorrhage: Mechanism and Intervention (CHEERY) study were entered into the analysis. Demographic information and clinical manifestations and outcomes were collected and compared between the 2 groups. RESULTS: From December 1, 2018, to November 30, 2020, a total of 3460 patients with ICH from the CHEERY study were enrolled and eventually analyzed. The results showed that during the COVID-19 pandemic, patients with ICH were more likely to be older (P<.001) with a history of ischemic stroke (P=.04), shorter time from onset to admission (P<.001), higher blood pressure (P<.001), higher fasting blood glucose (P=.003), larger hematoma volume (P<.001), and more common deep ICH (P=.01) and intraventricular hemorrhage (P=.02). These patients required more intensive care unit treatment (P<.001) and preferred to go to the hospital directly rather than call an ambulance (P<.001). In addition, the COVID-19 pandemic was associated with an increased risk of pulmonary infection during hospitalization (adjusted risk ratio [RRadjusted] 1.267, 95% CI 1.065-1.509), lower probability of a 3-month good outcome (RRadjusted 0.975, 95% CI 0.956-0.995), and a higher probability of in-hospital (RRadjusted 3.103, 95% CI 2.156-4.465), 1-month (RRadjusted 1.064, 95% CI 1.042-1.087), and 3-month (RRadjusted 1.069, 95% CI 1.045-1.093) mortality. CONCLUSIONS: Our study indicated that the cloud of COVID-19 has adversely impacted the presentation and outcomes of ICH. Medical workers may pay more attention to patients with ICH, while the public should pay more attention to hypertension control and ICH prevention. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900020872; https://www.chictr.org.cn/showprojEN.html?proj=33817.