Augmented type 2 inflammatory response in allergic rhinitis patients experiencing systemic reactions to house dust mite subcutaneous immunotherapy.

BACKGROUND: Subcutaneous immunotherapy (SCIT) can induce systemic reactions (SRs) in certain patients, but the underlying mechanisms remain to be fully elucidated. METHODS: AR patients who were undergoing standardized HDM SCIT (Alutard, ALK) between 2018 and 2022 were screened. Those who experienced two consecutive SRs were included in the study group. A control group was established, matched 1:1 by gender, age, and disease duration with the study group, who did not experience SRs during SCIT. Clinical and immunological parameters were recorded and analyzed both before SCIT and after 1 year of treatment. RESULTS: A total of 161 patients were included, with 79 (49.07%) in the study group. The study group had a higher proportion of AR combined asthma (26.8% vs. 51.8%, p < 0.001) and higher levels of sIgE to HDM and HDM components (all p < .001). Serum IL-4 and IL-13 levels in the study group were higher than those in the control group (p < .05). The study group received a lower maintenance dosage of HDM extracts injections than control group due to SRs (50000SQ vs. 100000SQ, p < .05). After 1 year of SCIT, the VAS score, the lung function parameters of asthmatic patients over 14 years old significantly improved in both groups (all p < .05). After a 7-day exposure to 20 µg/mL HDM extracts, the percentages of Th1, Th17, Tfh10, and Th17.1 in PBMCs decreased, while the Tfh13 cells significantly increased in the study group (p < .05). CONCLUSION: The type 2 inflammatory response is augmented in HDM-induced AR patients who experienced SRs during SCIT. Despite this, SCIT remains effective in these patients when administered with low-dosage allergen extracts.

Evidence of aberrant anti-epstein-barr virus antibody response, though no viral reactivation, in people with post-stroke fatigue.

BACKGROUND: Fatigue is a common complication of stroke that has a significant impact on quality of life. The biological mechanisms that underly post-stroke fatigue are currently unclear, however, reactivation of latent viruses and their impact on systemic immune function have been increasingly reported in other conditions where fatigue is a predominant symptom. Epstein-Barr virus (EBV) in particular has been associated with fatigue, including in long-COVID and myalgic encephalomyelitis/chronic fatigue syndrome, but has not yet been explored within the context of stroke. AIMS: We performed an exploratory analysis to determine if there is evidence of a relationship between EBV reactivation and post-stroke fatigue. METHODS: In a chronic ischemic stroke cohort (> 5 months post-stroke), we assayed circulating EBV by qPCR and measured the titres of anti-EBV antibodies by ELISA in patients with high fatigue (FACIT-F < 40) and low fatigue (FACIT-F > 41). Statistical analysis between two-groups were performed by t-test when normally distributed according to the Shapiro-Wilk test, by Mann-Whitney test when the data was not normally distributed, and by Fisher's exact test for categorical data. RESULTS: We observed a similar incidence of viral reactivation between people with low versus high levels of post-stroke fatigue (5 of 22 participants (24%) versus 6 of 22 participants (27%)). Although the amount of circulating EBV was similar, we observed an altered circulating anti-EBV antibody profile in participants with high fatigue, with reduced IgM against the Viral Capsid Antigen (2.244 ± 0.926 vs. 3.334 ± 2.68; P = 0.031). Total IgM levels were not different between groups indicating this effect was specific to anti-EBV antibodies (3.23 × 105 ± 4.44 × 104 high fatigue versus 4.60 × 105 ± 9.28 × 104 low fatigue; P = 0.288). CONCLUSIONS: These data indicate that EBV is not more prone to reactivation during chronic stroke recovery in those with post-stroke fatigue. However, the dysregulated antibody response to EBV may be suggestive of viral reactivation at an earlier stage after stroke.

A pH switchable hydrophilic fluorescent BODIPY sodium disulfonate for Fe3+ multicolor detection: Experimental and DFT studies.

BODIPY-based chemosensors are widely used owing to merits like good selectivity, high fluorescence quantum yield, and excellent optical stability. As such, a pH-switchable hydrophilic fluorescent probe, BODIPY-PY-(SO3Na)2, was developed for detection of Fe3+ ion in aqueous solutions. BODIPY-PY-(SO3Na)2 revealed strong fluorescence intensity and was responsive to pH value in the range of 6.59-1.96. Additionally, BODIPY-PY-(SO3Na)2 showed good selectivity and sensitivity towards Fe3+. A good linear relationship for Fe3+ detection was obtained from 0.0 µM to 50.0 µM with low detecting limit of 6.34 nM at pH 6.59 and 2.36 nM at pH 4.32, respectively. The response to pH and detection of Fe3+ induced obvious multicolor changes. BODIPY-PY-(SO3Na)2 can also be utilized to quantitatively detect Fe3+ in real water sample. Different mechanisms of Fe3+ detection at investigated pH values were unraveled through relativistic density functional theory (DFT) calculations in BODIPY-PY-(SO3Na)2 and experiments of coexisting cations, anions and molecules. These results enabled us to gain a deeper understanding of the interactions between BODIPY-PY-(SO3Na)2 and Fe3+ and provide valuable fundamental information for design of efficient multicolor chemosensors for Fe3+ as well.

Associations of air pollutants and related metabolites with preterm birth during pregnancy.

OBJECTIVE: This study aimed to investigate the influence of exposure to ambient fine particulate matter (PM2.5) and its components during pregnancy on the prevalence of preterm birth (PTB). Additionally, we sought to identify the susceptible exposure window. Furthermore, we explored the potential mediating role of blood analysis and a comprehensive metabolic panel in the association between pollutant exposure and PTB incidence. METHODS: This birth cohort study recruited 139 participants with PTB outcomes and 1713 controls from Fujian Maternal and Child Health Hospital between January 2021 and June 2023. Sociodemographic characteristics and clinical treatment data during participants' first pregnancies were collected. The exposure levels to pollutants during pregnancy were estimated via a combined geographic-statistical model utilising satellite remote sensing data. The distributional lag nonlinear modelling was employed to assess associations between pollutant exposure during pregnancy and the prevalence of PTB. Weighted quantile regression was used to identify key components associated with PM2.5 and PTB during pregnancy. Additionally, a mediating effect analysis was conducted to evaluate the role of blood analysis. The metabolic profile was used to screen for differentially abundant metabolites associated with PTB and explore their relative expression in relation to air pollutants and PTB incidence. RESULTS: Following the adjustment for potential confounding variables, the mean weekly susceptibility windows for PM2.5 were identified as 7-10, 16-19, and 22-28 weeks; 8-10, and 15-19 weeks for inorganic sulfate; 6-10, and 15-28 weeks for nitrate; 6-12, and 15-28 weeks for ammonium (NH4+); and 7-9, 18-20, and 22-36 weeks for organic matter. During mixed exposure to PM2.5 components, the key component is NH4+. In the mixed exposure to PM2.5 components, NH4+ emerged as a key contributor. The results of the mediation analysis revealed that haemoglobin played a mediating role, accounting for 21.53 % of the association between exposure to environmental pollutants and the prevalence of PTB. It is noteworthy that, no mediating effects were observed for the other variables. Furthermore, non-targeted metabolomics identified 17 metabolites associated with PTB. Among these factors, hydrogen phosphate may impact metabolic pathways such as oxidative phosphorylation, influencing the risk of PTB. The interplay between environmental pollutants and metabolites, particularly through oxidative phosphorylation pathways, may contribute to PTB incidence. CONCLUSIONS: The evidence indicates that exposure to PM2.5 and its components during pregnancy were a significant risk factor for PTB. Notably, specific weekly exposure windows were identified for pollutants during pregnancy. Among the PM2.5 components, NH4+ exhibited the most substantial weight in the association analysis between exposure to the mixture of components and PTB. Furthermore, our mediation analysis revealed that haemoglobin serves as a partial mediator in the relationship between exposure to pollutants during pregnancy and the prevalence of PTB. Additionally, maternal serum metabolic profiles differed between the preterm and control groups. Notably, a combined effect involving hydrogen phosphate and mixed exposure to PM2.5 fractions further contributed to the development of PTB. Oxidative phosphorylation pathways may play pivotal roles in this intricate association.

[Research status and reflection of the mechanism of TCM manipulation in the treatment of cervical spondylosis under the background of multi-disciplinary intersection].

The study of TCM manipulation's mechanism is the key scientific issue in the current manipulation research. It is the key and difficult point on the road of modernization and internationalization of Chinese orthopedics and traumatology. Meanwhile, it is also an important way to clarify systematically the scientific connotation of TCM manipulation. At present, our country is in an important period when multi-disciplinary intersection lead knowledge production, scientific innovation, and discipline development. The trend of cross-innovation between Chinese orthopedics and traumatology and other disciplines provides the carrier and method for the study of TCM manipulation's mechanism. Cervical spondylosis is the traditional dominant disease of Chinese orthopedics and traumatology. In recent years, many scholars have applied multi-disciplinary techniques and theories to explore the mechanism of TCM manipulation by focusing on the four dimensions of muscle, bone, blood vessel and nerve. The article takes the treatment of cervical spondylosis by TCM manipulation as the research entry point, and integrates the application status and implementation strategies of various techniques and theories under the background of multi-disciplinary intersection, which is conducive to the better combination, innovation and transformation of Chinese orthopedics and traumatology with other disciplines, and provides ideas and references for systematically clarifying the scientific connotation of TCM manipulation.

Tracheoplasty should be proactively considered within the surgical strategy for treating the ring-sling complex.

BACKGROUND: To examine the safety and effectiveness of proactive tracheoplasty for pediatric ring-sling complexes. METHODS: We retrospectively collected the data from 304 children who were diagnosed with a ring-sling complex and underwent surgery at three cardiac centers in China between January 2010 and June 2023. Children were categorized into three surgical groups: concurrent sling and tracheal surgery (Group A, n=258), staged sling and tracheal surgery (Group B, n=25), and sling-only surgery (Group C, n=21). We compared perioperative clinical characteristics, tracheal morphology changes, and outcomes across the groups. RESULTS: The median age of the children was 1.2 (IQR: 0.7-1.9) years. The anomalous tracheobronchial arborization rates were higher in Groups A (52.5%) and B (60.0%) than in Group C (15.0%). The preoperative narrow-wide ratio (NWR) was lower in Groups A and B than in Group C, with values of 0.44 (IQR: 0.35-0.52), 0.44 (0.33-0.59), and 0.68 (0.54-0.72), respectively (P<0.001). Preoperative subcarina angles were similar among the groups (P=0.54). After specific surgeries, the NWR and subcarina angle significantly improved in Groups A and B but not in Group C. There were seven in-hospital deaths and two post-discharge deaths. Respiratory symptoms improved in Groups A and B but seven children in Group C remained respiratory dysfunction. Six children presented with residual stenosis of the left pulmonary artery. CONCLUSION: Concurrent sling and tracheal surgeries for children with the ring-sling complex are safe and effective and are especially preferable for those with NWR ≤0.6, long-segment or diffuse tracheal stenosis, anomalous tracheobronchial arborization, and pronounced respiratory symptoms.

Landscape analysis of environmental data sources for linkage with SEER cancer patients database.

One of the challenges associated with understanding environmental impacts on cancer risk and outcomes is estimating potential exposures of individuals diagnosed with cancer to adverse environmental conditions over the life course. Historically, this has been partly due to the lack of reliable measures of cancer patients' potential environmental exposures before a cancer diagnosis. The emerging sources of cancer-related spatiotemporal environmental data and residential history information, coupled with novel technologies for data extraction and linkage, present an opportunity to integrate these data into the existing cancer surveillance data infrastructure, thereby facilitating more comprehensive assessment of cancer risk and outcomes. In this paper, we performed a landscape analysis of the available environmental data sources that could be linked to historical residential address information of cancer patients' records collected by the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. The objective is to enable researchers to use these data to assess potential exposures at the time of cancer initiation through the time of diagnosis and even after diagnosis. The paper addresses the challenges associated with data collection and completeness at various spatial and temporal scales, as well as opportunities and directions for future research.

Combining salivary α-synuclein seeding activity and miRNA-29a to distinguish Parkinson's disease and multiple system atrophy.

INTRODUCTION: The differential diagnosis of early Parkinson's disease (PD) by a single biomarker is still challenging due to its symptomatic overlap with other neurological diseases. Increasing evidences support the use of saliva biomarkers of neurodegeneration, including microRNAs and α-synuclein (α-syn) seeding activity, to diagnose patients with idiopathic PD and multiple system atrophy (MSA). Our previous study confirmed the salivary microRNA-29a-3p (miRNA-29a-3p) and α-syn seeding activity could differentiate PD and MSA from healthy control subjects (HCs) and patients with essential tremor (ET). METHODS: We set up α-syn real-time quaking induced conversion seed amplification assay (α-syn RT-QuIC SAA) in 203 participants from the Peking University First Hospital with PD (n = 101), MSA (n = 32), ET (n = 17) and healthy control subjects (HCs, n = 53). We also determined miRNA-29a-3p in saliva by real time quantitative PCR (RT-qPCR) and, in 155 participants (36HCs, 80PD, 22MSA, 17ET). RESULTS: Sensitivity of RT-QuIC seed amplification assay (SAA) for PD was 70.30 %, for MSA was 56.25 % and specificity for healthy controls was 92.45 %. The expression level of saliva miRNA-29a-3p was significantly decreased in patients with PD (p < 0.001) and MSA (p < 0.0001), and allowed differentiation with HCs (PD vs. HCs, AUC 0.69; MSA vs. HCs, AUC 0.95). Sensitivity of salivary miRNA-29a-3p for PD and MSA were 70.00 % and 95.45 %, respectively, and specificity for PD and MSA were 77.23 % and 80.56 %, respectively. By combining the salivary α-syn RT-QuIC SAA with miRNA-29a-3p, sensitivity for PD vs. HCs increasing to 75.00 %, while sensitivity for MSA vs. HCs increasing to 90.00 %. Specificity was 91.67 % for PD and 88.89 % for MSA after combining assessment of salivary α-syn RT-QuIC SAA. Salivary α-syn RT-QuIC SAA yielded 100.00 % sensitivity and 79.21 % specificity for PD vs. ET, and 100.00 % sensitivity and 65.63 % specificity for MSA vs. ET. Salivary miRNA-29a-3p provied 88.24 % sensitivity and 48.75 % specificity for PD vs. ET and 86.36 % sensitivity and 88.24 % specificity for MSA vs. ET. The combined assessment of saliva markers provided a better diagnostic value for ET vs. synucleinopathies (ET vs. PD: 88.24 % sensitivity and 81.25 % specificity; ET vs. MSA: 94.12 % sensitivity and 90.00 % specificity) than RT-QuIC SAA alone, or miRNA-29a-3p alone. The combination of lag phase and miRNA-29a-3p could add higher specificity (85.71 %) which increased approximately 40 percent (specificity: miRNA-29a-3p 47.50 %, lag phase 48.98 %) for discriminating PD from MSA. However, the sensitivity of combining these two methods was 61.11 %, which was lower than lag phase alone (89.66 %) or miRNA-29a-3p alone (95.45 %). CONCLUSIONS: This study confirmed that saliva, a non-invasive biofluid in synucleinopathies possessed potential diagnostic power between PD, MSA, ET and normal controls. We show the combined value of saliva miRNA-29a-3p and saliva α-syn RT-QuIC SAA in the diagnosis and differential diagnosis of Parkinsonism.

Lecithin-cholesterol acyltransferase is a potential tumor suppressor and predictive marker for hepatocellular carcinoma metastasis.

BACKGROUND: Hepatocellular carcinoma (HCC) is a major cause of cancer mortality worldwide, and metastasis is the main cause of early recurrence and poor prognosis. However, the mechanism of metastasis remains poorly understood. AIM: To determine the possible mechanism affecting HCC metastasis and provide a possible theoretical basis for HCC treatment. METHODS: The candidate molecule lecithin-cholesterol acyltransferase (LCAT) was screened by gene microarray and bioinformatics analysis. The expression levels of LCAT in clinical cohort samples was detected by quantitative real-time polymerase chain reaction and western blotting. The proliferation, migration, invasion and tumor-forming ability were measured by Cell Counting Kit-8, Transwell cell migration, invasion, and clonal formation assays, respectively. Tumor formation was detected in nude mice after LCAT gene knockdown or overexpression. The immunohistochemistry for Ki67, E-cadherin, N-cadherin, matrix metalloproteinase 9 and vascular endothelial growth factor were performed in liver tissues to assess the effect of LCAT on HCC. Gene set enrichment analysis (GSEA) on various gene signatures were analyzed with GSEA version 3.0. Three machine-learning algorithms (random forest, support vector machine, and logistic regression) were applied to predict HCC metastasis in The Cancer Genome Atlas and GEO databases. RESULTS: LCAT was identified as a novel gene relating to HCC metastasis by using gene microarray in HCC tissues. LCAT was significantly downregulated in HCC tissues, which is correlated with recurrence, metastasis and poor outcome of HCC patients. Functional analysis indicated that LCAT inhibited HCC cell proliferation, migration and invasion both in vitro and in vivo. Clinicopathological data showed that LCAT was negatively associated with HCC size and metastasis (HCC size ≤ 3 cm vs 3-9 cm, P < 0.001; 3-9 cm vs > 9 cm, P < 0.01; metastatic-free HCC vs extrahepatic metastatic HCC, P < 0.05). LCAT suppressed the growth, migration and invasion of HCC cell lines via PI3K/AKT/mTOR signaling. Our results indicated that the logistic regression model based on LCAT, TNM stage and the serum level of α-fetoprotein in HCC patients could effectively predict high metastatic risk HCC patients. CONCLUSION: LCAT is downregulated at translational and protein levels in HCC and might inhibit tumor metastasis via attenuating PI3K/AKT/mTOR signaling. LCAT is a prognostic marker and potential therapeutic target for HCC.

Lactobacillus casei Cell Wall Extract and Production of Galactose-Deficient IgA1 in a Humanized IGHA1 Mouse Model.

BACKGROUND: IgA nephropathy is the most common primary glomerulonephritis worldwide, and there is emerging evidence linking galactose-deficient IgA1 (Gd-IgA1) to the pathogenesis of the disease. However, mouse models that can be used to study Gd-IgA1's origin of production, biochemical characteristics, and immune reactivity are lacking. METHODS: We generated a humanized IgA1 mouse model with transgenic expression of the human IGHA1 gene from the mouse chromosomal locus of IgA heavy chain. The IGHA1+/+ mice were crossed with complement factor H heterozygous mutant (FHW/R) to generate IGHA1+/+FHW/R mice. IGHA1+/+ mice were exposed to different levels of environmental pathogens in the first 4 months, as housed in either germ-free, specific pathogen-free, or conventional environments. In addition, wild-type C57BL/6J mice, IGHA1+/+ mice, and IGHA1+/+FHW/R mice were inoculated with Lactobacillus casei cell bacterial wall extract (LCWE) mixed with complete Freund's adjuvant (CFA) at two months of age to develop a mouse model of IgA nephropathy. RESULTS: Elevated levels of human IgA1 in blood circulation and mucosal sites were observed in IGHA1+/+ mice from exposure to pathogens. Compared to buffer-treated control mice, LCWE plus CFA-treated mice had moderately elevated levels of circulating human IgA1 (by one fold) and human IgA1 immune complexes (by two folds). Serum Gd-IgA1 levels increased fourfold following LCWE treatments. Analyses of the O-glycopeptides of the IgA1 hinge region confirmed hypo-galactosylation of IgA1, with the variety of the glycoforms matching those seen in clinical samples. Furthermore, LCWE induced persistent IgA1 and C3 deposition in the glomerular mesangial areas in association with mesangial expansion and hypercellularity, which are frequently observed in IgA nephropathy biopsies. The IGHA1+/+FHW/R mice stimulated with LCWE and CFA developed albuminuria and hematuria. CONCLUSIONS: We observed elevated plasma Gd-IgA1 levels with kidney deposition of IgA1 in the IGHA1+/+ mice following LCWE and CFA. In conjunction with factor H mutation, the mice exhibited severe glomerular alterations, associated with hematuria and albuminuria in resemblance of clinical IgA nephropathy.

Continuous therapy in HHV-8 negative Multicentric Castleman Disease and prolonged progression-free survival.

The optimal treatment endpoints and duration of continuous therapy for multicentric Castleman disease (MCD) remain controversial. We retrospectively analyzed data from 123 patients with Human Herpesvirus (HHV)-8 negative MCD. We demonstrated that continuous therapy significantly enhanced progression-free survival (PFS) in patients who achieved an optimal response after initial treatment. These findings underscore the critical role of continuous therapy in HHV-8 negative MCD. Further studies with larger cohorts are required to validate these findings.

[Clinical effect of MB-PDT assisted initial therapy on alveolar angle absorption of lower anterior teeth].

PURPOSE: To evaluate the effect of MB-PDT assisted essential therapy on angle resorption of lower anterior alveolar bone in patients with periodontitis. METHODS: Forty patients who were diagnosed with periodontitis stage III-IV or C, lower anterior teeth alveolar bone angle resorption, and periodontal pocket depth greater than 4 mm were selected from April 2018 to October 2020 in the Department of Periodontology and Oral Mucosal Diseases, Changsha Stomatological Hospital. The patients were randomly divided into control group and experimental group with 20 cases in each group. Compared with the control group which was only managed with essential treatment, the experimental group was treated with MB-PDT on the basis of the control group. The plaque index (PLI) and gingival bleeding index (GBI) scores of the two groups were recorded before surgery and 1 and 2 weeks after surgery. Probing depth (PD) and clinical attachment level (CAL) were detected before and 6 months after surgery. Statistical analysis of the data was performed using Graphpad Prism 5 software package. RESULTS: The PLI and GBI of the experimental group were significantly lower than those of the control group at 1 and 2 weeks after operation(P＜0.05). Six months after surgery, PD and CAL levels in the experimental group were significantly lower than those in the control group (P＜0.05). CONCLUSIONS: MB-PDT adjuvant therapy has the advantages of simple operation, efficient sterilization, promotion of healing, and high safety performance. It may be a new non-surgical adjuvant treatment strategy for effective treatment of lower anterior alveolar angular resorption.

Light-regulated soliton dynamics in liquid crystals.

Electrically powered solitons are particle-like field configurations in out-of-equilibrium nematics that have garnered significant interest. However, their random generation and lack of controllable motion have limited their application. Here, we present a reconfigurable optoelectronic approach capable of regulating the entire lifecycle of solitons by utilizing multi-strategy digital light projection to construct delicate patterning of virtual electrode. We demonstrate that optically actuated domains with diverse geometry enable the generation of multiple solitons and further allow in-situ formation of individual soliton by matching the light pattern to its dimension. Exquisitely engineered light intensity of patterns facilitates modulation of soliton velocity and transformation of propagating direction. The utilization of a light-guided channel enables the on-demand control of soliton trajectories along customized paths. Furthermore, dynamic light patterns that vary in space and time allow for collective motion such as migration, mimicking phototaxis in biological systems. This reconfigurable manipulation strategy, grounded in the photoconductive effect, proves highly versatile and effective in directing soliton dynamics, heralding the potential for their programmable control and offering a significant advantage in multitasking scenarios.

A Click-Type Enzymatic Method for Antigen-Adjuvant Conjugation.

The Toll-like receptor 9 (TLR9) stimulator, CpG oligodeoxynucleotide, has emerged as a potent enhancer of protein subunit vaccines. Incorporating the protein antigen directly with the CpG adjuvant presents a novel strategy to significantly reduce the required dosage of CpG compared to traditional methods that use separate components. In contrast to existing chemical conjugation methods, this study introduces an enzymatic approach for antigen-adjuvant coupling using a recombinant endonuclease DCV fused with SpyTag. This fusion protein catalyzes the covalent linkage between itself and the CpG adjuvant under mild conditions. These conjugates can be further linked with target protein antigens containing the SpyCatcher sequence, yielding stable, covalently-linked antigen-adjuvant complexes. The corresponding complex utilizing the receptor-binding domain (RBD) of SARS-CoV-2 spike protein as the model antigen, elicits high-titer, specific antibody production in mice via both subcutaneous administration and intratracheal inoculation. Notably, the tumor vaccine candidate fabricated by this method has also shown significant inhibition of cancer progression after intratracheal administration. The technique ensures precise, site-specific coupling and preserves the antigen's structural integrity due to the post-purification coupling strategy that simplifies manufacturing and aids in developing inhalable vaccines.

Photoinduced Deoxygenative C2 Arylation of Quinoline N-oxides with Phenylhydrazines to 2-Arylquinolines over Porous Tubular Graphitic Carbon Nitride Semiconductor Photocatalyst.

The photo-induced deoxygenative C2 arylation of quinoline N-oxides to 2-arylquinolines is achieved over a heterogeneous porous tubular graphitic carbon nitride (PTCN) catalyst with phenylhydrazines as arylation reagent. A wide range of quinoline N-oxides can be efficiently transformed into their corresponding 2-arylquinolines under visible light irradiation. Moreover, PTCN catalyst is easily separated and could be reused several times without loss to its original activity.

Unmasking of molecular players: proteomic profiling of vitreous humor in pathologic myopia.

BACKGROUND: This study aimed to identify the differentially expressed proteins in the vitreous humor (VH) of eyes with and without pathologic myopia (PM), providing insights into the molecular pathogenesis. METHODS: A cross-sectional, observational study was conducted. VH samples were collected from patients undergoing vitrectomy for idiopathic epiretinal membrane (ERM), macular hole (MH), or myopic retinoschisis (MRS). Label-free quantitative proteomic analysis identified differential protein expression, with validation using ELISA. RESULTS: The proteomic profiling revealed significantly higher expressions of tubulin alpha 1a (TUBA1A) and eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) in PM groups (MH-PM, MRS-PM) compared to controls (MH, ERM). Conversely, xylosyltransferase 1 (XYLT1), versican core protein (VCAN), and testican-2 (SPOCK2) expressions were lower in PM. ELISA validation confirmed these findings. CONCLUSIONS: Our study provides novel insights into the molecular mechanisms of PM. The differentially expressed proteins EEF1A1, TUBA1A, XYLT1, VCAN, and SPOCK2 may play crucial roles in chorioretinal cell apoptosis, scleral extracellular matrix (ECM) synthesis, and scleral remodeling in PM. These proteins represent potential new targets for therapeutic intervention in PM, highlighting the importance of further investigations to elucidate their functions and underlying mechanisms in disease pathogenesis.

Red Blood Cell Membrane Spontaneously Coated Nanoprodrug Based on Phosphatidylserine for Antiatherosclerosis Applications.

Atherosclerosis (AS) is characterized by the accumulation of lipids within the walls of coronary arteries, leading to arterial narrowing and hardening. It serves as the primary etiology and pathological basis for cardiovascular diseases affecting the heart and brain. However, conventional pharmacotherapy is constrained by inadequate drug delivery and pronounced toxic side effects. Moreover, the inefficacy of nanomedicine delivery systems in controlling disease progression may be attributed to nonspecific clearance by the mononuclear phagocyte system. Thus, a biomimetic platform spontaneously enveloped by red blood cell membrane is exploited for anti-atherosclerosis applications, offering favorable biocompatibility. The CLIKKPF polypeptide is introduced to develop red blood cell membrane spontaneously encapsulated nanotherapeutics only through simple coincubation. Given the functional modifications, RBC@P-LVTNPs is beneficial to facilitate the target drug delivery to the atherosclerotic lesion, responding precisely to the pathological ROS accumulation, thereby accelerating the on-demand drug release. Both in vivo and in vitro results also confirm the significant therapeutic efficacy and favorable biocompatibility of the biomimetic nanomedicine delivery system, thus providing a promising candidate for nanotherapeutics against AS.

Hippocampal HDAC5-mediated histone acetylation underlies stress susceptibility in mice exposed to chronic social defeat stress.

Chronic stress leads to social avoidance and anhedonia in susceptible individuals, a phenomenon that has been observed in both human and animal models. Nevertheless, the underlying molecular mechanisms underpinning stress susceptibility and resilience remain largely unclear. There is growing evidence that epigenetic histone deacetylase (HDAC) mediated histone acetylation is involved in the modulation of depressive-related behaviors. We hypothesized that histone deacetylase 5 (HDAC5), which is associated with stress-related behaviors and antidepressant response, may play a vital role in the susceptibility to chronic stress. In the current study, we detected the levels of HDAC5 and acetylation of histone 4 (H4) in the hippocampus subsequent to chronic social defeat stress (CSDS) in C57BL/6J mice. We found that CSDS induces a notable increase in HDAC5 expression, concomitant with a reduction in the acetylation of histone H4 at lysine 12 (H4K12) in the hippocampus of susceptible mice. Meanwhile, intrahippocampal infusion of HDAC5 shRNA or HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) both reversed the depression susceptibility in susceptible mice that subjected to CSDS. Furthermore, HDAC5 overexpression was sufficient to induce depression susceptibility following microdefeat stress, accompanied by a significant reduction in H4K12 level within the hippocampus of mice. Additionally, the Morris water maze (MWM) results indicated that neither CSDS nor HDAC5 exerted significant effects on spatial memory function in mice. Taken together, these investigations indicated that HDAC5-modulated histone acetylation is implicated in regulating the depression susceptibility, and may be serve as potential preventive targets for susceptible individuals.

Vitamin D receptor attenuates carbon tetrachloride-induced liver fibrosis via downregulation of YAP.

Liver fibrosis is characterized by the excessive accumulation of extracellular matrix proteins, which can lead to cirrhosis and liver cancer. Metabolic dysfunction-associated steatosis liver diseases are common causes of liver fibrosis, sharing a similar pathogenesis with carbon tetrachloride (CCl4) exposure. This process involves the activation of hepatic stellate cells (HSCs) into myofibroblasts. However, the detailed mechanism and effective treatment strategies require further investigation. In this study, we uncovered a negative correlation between VDR expression and YAP within HSCs. Subsequently, we demonstrated that VDR exerted a downregulatory influence on YAP transcriptional activity in HSCs. Intriguingly, activation VDR effectively inhibited the culture induced activation of primary HSCs by suppressing the transcriptional activity of early YAP. Furthermore, in vivo results manifested that hepatic-specific deletion of YAP/TAZ ameliorates CCl4-induced liver fibrosis, and nullified the antifibrotic efficacy of VDR. Importantly, a YAP inhibitor rescued the exacerbation of liver fibrosis induced by hepatic-specific VDR knockout. Moreover, the combined pharmacological of VDR agonist and YAP inhibitor demonstrated a synergistic effect in diminishing CCl4-induced liver fibrosis, primary HSCs activation and hepatic injury in vivo. These effects were underpinned by their collective ability to inhibit HSC activation through AMPK activation, consequently curbing ATP synthesis and HSCs proliferation. In conclusion, our results not only revealed the inhibition of VDR on YAP-activated liver stellate cells but also identified a synergistic effect of VDR agonist and YAP inhibitor in an AMPKα-dependent manner, providing a practical foundation for integration of multi-targeted drugs in the therapy of CCl4-induced hepatic fibrosis.