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1.
Eur J Pediatr ; 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38822834

Congenital heart disease (CHD) and patent ductus arteriosus (PDA) are risk factors of necrotizing enterocolitis (NEC) in infants. However, it is unclear whether the prognosis of NEC is different between very preterm infants (VPIs) with and without heart diseases. This was an observational cohort study that enrolled VPIs (born between 24+0 and 31+6 weeks) admitted to 79 tertiary neonatal intensive care units (NICU) in the Chinese Neonatal Network (CHNN) between 2019 and 2021. The exposure was CHD or isolated PDA, and VPIs with NEC were divided into three groups: complicated with CHD, with isolated PDA, and without heart diseases. The primary outcomes were NEC-related adverse outcomes (death or extrauterine growth restriction (EUGR)). Logistic regression models were used to adjust potential confounders and calculate the odds ratios (ORs) and 95% confidential intervals (CIs) for each outcome. A total of 1335 VPIs with NEC were enrolled in this study, including 65 VPIs with CHD and 406 VPIs with isolated PDA. The VPIs with heart diseases had smaller gestational ages and lower body weights at birth, more antenatal steroids use, and requiring inotrope prior to the onset of NEC. While suffering from NEC, there was no significant increased risks in NEC-related death in VPIs with either CHD (adjusted OR [aOR]: 1.10; 95% CI: 0.41-2.50) or isolated PDA (aOR: 1.25; 95% CI 0.82-1.87), and increased risks in EUGR were identified in either survival VPIs with CHD (aOR: 2.35; 95% CI: 1.31-4.20) or isolated PDA (aOR: 1.53; 95% CI: 1.16-2.01) in survivors. The composite outcome (death or EUGR) was also more often observed in VPIs with either CHD (aOR: 2.07; 95% confidence interval [CI]: 1.20-3.60) or isolated PDA (aOR: 1.51; 95% CI: 1.17-1.94) than that without heart diseases. VPIs with either CHD or isolated PDA were associated with significantly prolonged duration of fasting, extended time to achieve full enteral feeding, and longer ventilation duration and hospitalization duration. Similar characteristics were also seen in VPIs with isolated PDA, with the exception that VPIs with CHD are more likely to undergo surgical intervention and maintain a prolonged fast after NEC.     Conclusion: In VPIs with NEC, CHD and isolated PDA are associated with an increased risk in worse outcomes. We recommend that VPIs with cardiac NEC be managed with aggressive treatment and nutrition strategies to prevent EUGR. What is Known: • CHD and PDA are risk factors for NEC in infants, which can lead to adverse outcomes such as death and EUGR. • NEC in infants with heart disease differs clinically from that in infants without heart disease and should be recognized as a separate disease process. What is New: • CHD and isolated PDA are associated with increased risks of EUGR in VPIs with NEC. • Risk factors associated with VPIs with cardiac NEC suggested these patients should be managed with aggressive treatment and nutrition strategies to adverse outcomes.

2.
Int J Lab Hematol ; 2024 Jun 02.
Article En | MEDLINE | ID: mdl-38826023

INTRODUCTION: The purpose of this study was to investigate the effects and potential mechanisms of ferroptosis-related gene heat shock protein beta-1 (HSPB1) on acute myeloid leukemia (AML). METHODS: The RNA-seq and clinical data of AML samples were obtained from the Genomic Data Commons database, and the FerrDb database was used to screen the marker, drive and suppressor of ferroptosis. Besides, DESeq2 was applied for differential expression analysis on AML samples and screening for differentially expressed genes (DEGs). The screened DEGs were subjected to the intersection analysis with ferroptosis-related genes to identify the ferroptosis-related DEGs. Next, the functional pathways of ferroptosis-related DEGs were further be discussed by Gene Ontology as well as Kyoto Encyclopedia of Genes and Genomes enrichment analysis of DEGs. Additionally, lasso regression analysis was employed to determine the differential genes related to prognosis in patients with AML and the survival analysis was performed. Subsequently, quantitative real-time polymerase chain reaction and western blot assay were applied to detect the mRNA and protein expression levels of HSPB1 in normal/AML bone marrow tissues and human normal (HS-5)/AML (HL-60) bone marrow cells, respectively. Furthermore, HSPB1 was knocked down to assess the expression changes of glutathione peroxidase 4 and acyl-CoA synthetase long-chain family member 4. Ultimately, the viability and oxidative stress levels of HL-60 were analyzed by Cell Counting Kit-8 and biochemical detection. RESULTS: A total of 4986 DEGs were identified in AML samples, with 3324 up-regulated and 1662 down-regulated. The enrichment analysis illustrated that ferroptosis-related DEGs were significantly enriched in response to metal irons, oxidative stress, and other pathways. After lasso regression analysis, 17 feature genes related to the prognosis of patients with AML were obtained, with HSPB1 exhibiting a significant correlation. The reliability of our models was verified by Cox regression analysis and survival analysis of the hazard model. Furthermore, the outcomes of quantitative real-time polymerase chain reaction and western blot showed that mRNA and protein expression levels of HSPB1 were significantly increased in the AML Group and HL-60 cells. The knockdown of HSPB1 in HL-60 cells reduced the protein level of glutathione peroxidase 4, increased the protein level of acyl-CoA synthetase long-chain family member 4, decreased the cell viability, and aggravated oxidative stress. CONCLUSION: Ferroptosis-related gene HSPB1 is highly expressed in patients with AML. In addition, HSPB1 may be involved in the occurrence and development of AML by regulating oxidative stress and ferroptosis-related pathways. This study provides new clues for further understanding of AML molecular mechanisms. Also, HSPB1 is expected to be a potential therapeutic target for AML in the future.

3.
Gynecol Endocrinol ; 40(1): 2358219, 2024 Dec.
Article En | MEDLINE | ID: mdl-38835150

OBJECTIVES: Polycystic ovary syndrome (PCOS) and subclinical hypothyroidism (SCH) are prevalent gynecological conditions. However, the interrelationship between the two remains elusive. This study aims to elucidate the association between these conditions and determine the potential impact of SCH on the physiological and metabolic characteristics of patients with PCOS. METHODS: This cross-sectional study enrolled 133 patients with PCOS from our Hospital. Participants were categorized into two groups: those with PCOS + SCH (n = 58) and those with PCOS (n = 75). Serum hormonal levels, metabolic markers, ovarian volume, and follicle count were compared between the groups. RESULTS: There was a significant difference in BMI between the two groups, with a higher prevalence of obesity in the PCOS + SCH group (p = .014). Compared to the PCOS group, patients with PCOS + SCH had significantly higher levels of TSH (p < .001), triglycerides (p = .025), and HOMA-IR (p < .001), while LH levels were significantly lower (p = .048). However, multivariate linear regression analysis revealed that TSH, triglycerides, LH, and HOMA-IR were not determinants for the occurrence of SCH in patients with PCOS. Additionally, there was a notable reduction in follicle count in the left ovary for the PCOS + SCH group compared to the PCOS group (p = .003), and the overall follicle diameter of the PCOS + SCH group was also smaller (p = .010). CONCLUSION: SCH may exert effects on the physiological and metabolic profiles of patients with PCOS. Further investigation into the relationship between these disorders is warranted to delineate their clinical implications.


Hypothyroidism , Ovary , Polycystic Ovary Syndrome , Humans , Polycystic Ovary Syndrome/blood , Polycystic Ovary Syndrome/metabolism , Polycystic Ovary Syndrome/complications , Female , Hypothyroidism/blood , Hypothyroidism/complications , Cross-Sectional Studies , Adult , Ovary/pathology , Ovary/metabolism , Ovary/diagnostic imaging , Young Adult , Thyrotropin/blood , Insulin Resistance/physiology , Luteinizing Hormone/blood , Body Mass Index , Triglycerides/blood , Ovarian Follicle/diagnostic imaging , Ovarian Follicle/metabolism
4.
Curr Res Food Sci ; 8: 100775, 2024.
Article En | MEDLINE | ID: mdl-38840808

Hydrocolloids have proven effective in improving the texture of surimi gels, yet their application in plant-based seafood analogues remains underexplored. This study aimed to develop a hydrocolloid blend comprising methylcellulose (MC), curdlan gum (CG), and high-acyl gellan gum (GG) to achieve a surimi-like texture in plant-based fish cakes (PBFC) made from brown rice and pea protein isolates. The research showcased that higher MC concentration boosted protein powder's heated oil holding capacity, while CG concentration increments lowered it. However, heated water holding capacity remained stable despite changes in MC and GG levels. Incorporating hydrocolloids elevated PBFC moisture content, decreasing expressible moisture and oil amounts with rising MC, CG and GG concentrations. PBFC hardness increased with higher hydrocolloid levels and was influenced by temperature, while springiness remained unaffected. GG helped maintain storage modulus (G') during PBFC cooling at higher concentrations, whereas the opposite effect was observed for MC. Analytically, higher MC concentrations reduced protein digestibility, while increased GG concentrations appeared to enhance it. Microstructural analysis corroborated these findings, with more protein aggregates in PBFC containing 3.8% MC and fewer in PBFCs with 6% CG and 3% GG. Consumer evaluations indicated that PBFC formulated with 1% MC, 3% CG, and 1.5% GG matched the springiness of commercial surimi-tofu fish cake, though it received slightly lower overall liking scores. In conclusion, the combined use of these three hydrocolloids demonstrated the potential to enhance the physical properties of PBFC and modify protein digestibility, offering insights into the development of innovative plant-based seafood analogues.

5.
Int J Nanomedicine ; 19: 5071-5094, 2024.
Article En | MEDLINE | ID: mdl-38846644

Background: The commercial docetaxel (DTX) formulation causes severe side effects due to polysorbate 80 and ethanol. Novel surfactant-free nanoparticle (NP) systems are needed to improve bioavailability and reduce side effects. However, controlling the particle size and stability of NPs and improving the batch-to-batch variation are the major challenges. Methods: DTX-loaded bovine serum albumin nanoparticles (DTX-BSA-NPs) were prepared by a novel thermal-driven self-assembly/microfluidic technology. Single-factor analysis and orthogonal test were conducted to obtain the optimal formulation of DTX-BSA-NPs in terms of particle size, encapsulation efficiency (EE), and drug loading (DL). The effects of oil/water flow rate and pump pressure on the particle size, EE, and DL were investigated to optimize the preparation process of DTX-BSA-NPs. The drug release, physicochemical properties, stability, and pharmacokinetics of NPs were evaluated. Results: The optimized DTX-BSA-NPs were uniform, with a particle size of 118.30 nm, EE of 89.04%, and DL of 8.27%. They showed a sustained release of 70% over 96 hours and an increased stability. There were some interactions between the drug and excipients in DTX-BSA-NPs. The half-life, mean residence time, and area under the curve (AUC) of DTX-BSA-NPs increased, but plasma clearance decreased when compared with DTX. Conclusion: The thermal-driven self-assembly/microfluidic combination method effectively produces BSA-based NPs that improve the bioavailability and stability of DTX, offering a promising alternative to traditional formulations.


Biological Availability , Docetaxel , Drug Stability , Nanoparticles , Particle Size , Serum Albumin, Bovine , Docetaxel/pharmacokinetics , Docetaxel/chemistry , Docetaxel/administration & dosage , Animals , Serum Albumin, Bovine/chemistry , Serum Albumin, Bovine/pharmacokinetics , Serum Albumin, Bovine/administration & dosage , Nanoparticles/chemistry , Taxoids/pharmacokinetics , Taxoids/chemistry , Taxoids/administration & dosage , Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/chemistry , Antineoplastic Agents/administration & dosage , Drug Liberation , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , Rats, Sprague-Dawley , Male , Drug Compounding/methods , Rats
6.
ChemSusChem ; : e202400650, 2024 Jun 08.
Article En | MEDLINE | ID: mdl-38850152

A convenient and sustainable method for synthesizing sulfonyl-containing compounds through a catalyst-free aqueous-phase hydrosulfonylation of alkenes and alkynes with sulfonyl chlorides under visible light irradiation is presented. Unactivated alkenes, electron-deficient alkenes, alkyl and aryl alkynes can be hydrosulfonylated with various sulfonyl chlorides at room temperature with excellent yields and geometric selectivities by using tris(trimethylsilyl)silane as a hydrogen atom donor and silyl radical precursor to activate sulfonyl chlorides. Mechanistic studies revealed that the photolysis of tris(trimethylsilyl)silane in aqueous solution to produce silyl radical is crucial for the success of this reaction.

7.
Comput Biol Med ; 178: 108686, 2024 Jun 04.
Article En | MEDLINE | ID: mdl-38850956

Iron-binding protein (Ibp) has protective effect on pathogen exposed to H2O2 in defense response of plants. Ibp in Botrytis cinerea (BcIbp) is related to its virulence. Bcibp mutation lead to virulence deficiencies in B. cinerea. BcIbp is involved in the Fe3+ homeostasis regulation. Recognition the binding site and binding pattern of ferric iron and iron-binding protein in B. cinerea are vital to understand its function. In this study, molecular dynamics (MD) simulations, gaussian accelerated molecular dynamics (GaMD) simulations, dynamic cross correlation analysis and quantum chemical energy calculation were used to explore binding pattern of ferric iron. MD results showed that the C-terminal region had little effect on the stability of residues in the Fe3+-binding pocket. Energy calculations suggested the most likely coordination pattern for ferric iron in iron-binding protein. These results will help to understand the binding of ferric iron to iron-binding protein and provide new ideas for regulating the virulence of B. cinerea.

8.
Signal Transduct Target Ther ; 9(1): 143, 2024 Jun 07.
Article En | MEDLINE | ID: mdl-38844468

Metastatic pancreatic cancer (mPC) has a dismal prognosis. Herein, we conducted a prospective, multicentre, single-arm, phase II trial evaluating the efficacy and safety of penpulimab and anlotinib in combination with nab-paclitaxel/gemcitabine (PAAG) in patients with first-line mPC (NCT05493995). The primary endpoints included the objective response rate (ORR) and disease control rate (DCR), while secondary endpoints encompassed progression-free survival (PFS), overall survival (OS), and safety. In 66 patients analysed for efficacy, the best response, indicated by the ORR, was recorded at 50.0% (33/66) (95% CI, 37.4-62.6%), with 33 patients achieving partial response (PR). Notably, the DCR was 95.5% (63/66, 95% CI, 87.3-99.1%). The median PFS (mPFS) and OS (mOS) were 8.8 (95% CI, 8.1-11.6), and 13.7 (95% CI, 12.4 to not reached) months, respectively. Grade 3/4 treatment-related adverse events (TRAEs) were reported in 39.4% of patients (26/66). In prespecified exploratory analysis, patients with altered SWI/SNF complex had a poorer PFS. Additionally, low serum CA724 level, high T-cell recruitment, low Th17 cell recruitment, and high NK CD56dim cell scores at baseline were potential predicative biomarkers for more favourable efficacy. In conclusion, PAAG as a first-line therapy demonstrated tolerability with promising clinical efficacy for mPC. The biomolecular findings identified in this study possess the potential to guide the precise clinical application of the triple-combo regimen.


Albumins , Antineoplastic Combined Chemotherapy Protocols , Deoxycytidine , Gemcitabine , Indoles , Paclitaxel , Pancreatic Neoplasms , Quinolines , Humans , Male , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Female , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Paclitaxel/pharmacology , Middle Aged , Aged , Deoxycytidine/analogs & derivatives , Deoxycytidine/administration & dosage , Indoles/administration & dosage , Indoles/therapeutic use , Albumins/administration & dosage , Albumins/adverse effects , Quinolines/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Prospective Studies , Adult , Neoplasm Metastasis , Angiogenesis Inhibitors/adverse effects , Angiogenesis Inhibitors/therapeutic use , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/pharmacology , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/therapeutic use , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/immunology
11.
Clin Exp Immunol ; 2024 May 14.
Article En | MEDLINE | ID: mdl-38743453

Serum B-cell maturation antigen (sBCMA) levels can serve as a sensitive biomarker in multiple myeloma (MM). In the research setting, sBCMA levels can be accurately detected by enzyme-linked immunosorbent assay (ELISA), but the approach has not been approved for clinical use. Here, we used a novel chemiluminescence method to assess sBCMA levels in 759 serum samples from 17 healthy donors and 443 patients with plasma cell (PC) diseases including AL amyloidosis, POEMS syndrome and MM. Serum BCMA levels were elevated 16.1-fold in patients with newly diagnosed MM compared to healthy donors and rare PC diseases patients. Specifically, the sBCMA levels in patients with progressive disease were 64.6-fold higher than those who showed partial response or above to treatment. The sBCMA level also correlated negatively with the response depth of MM patients. In newly diagnosed and relapsed MM patients, survival was significantly longer among those subjects whose sBCMA levels are below the median levels compared with those above the median value. We optimized the accuracy of the survival prediction further by integrating sBCMA level into the Second Revised International Staging System (R2-ISS). Our findings provide evidence that the novel chemiluminescence method is sensitive and practical for measuring sBCMA levels in clinical samples and confirm that sBCMA might serve as an independent prognostic biomarker for MM.

12.
Heliyon ; 10(9): e29987, 2024 May 15.
Article En | MEDLINE | ID: mdl-38737278

Objective: The study analyzed the impact of urbanization on epidemiological characteristics of respiratory infectious disease in Tongzhou District, Beijing during 2014-2022 to provide reference for prevention and control priorities of respiratory infectious diseases during the innovative urbanization process in China. Methods: The incidence data of notifiable respiratory infectious diseases (NRIDs) in Tongzhou Beijing during 2014-2022 were summarized. The trend of incidence rate was analyzed by Joinpoint regression model, and entropy method was performed to construct the comprehensive index of urbanization (CIU) and generalized linear model was used to analyze the influence of CIU on the incidence rate of respiratory infectious diseases. Results: Totally 72616 NRIDs cases were reported in Tongzhou District during 2014-2022, and the incidence rate of NRIDs was higher during 2017-2019 (153/100 000) than during 2014-2016 (930/100 000) and during 2020-2022 (371/100 000), respectively (both P < 0.001). The CIU constantly increased with slight fluctuation in 2016 and 2018, respectively. The incidence rate of NRIDs showed an increase along with the CIU during 2014-2019 (r = 0.95, P = 0.004), while the incidence rate's tendency was interrupted by COVID-19 during 2020 with slight decrease in 2020-2021 and rebounded in 2022. For the patients aged <15 years, the incidence rate of NRIDs revealed a very sharp rise at the urbanization period without COVID-19 pandemic compared with that under pre-urbanization period (RR = 7.93, 95 % CI 7.63-8.24), and dropped off to the similar level as of pre-urbanization period when COVID-19 pandemic spread. Conclusions: Urbanization process may increase the incidence of NRIDs but constrained by COVID-19. Certain measures should be taken to prevent and control the effects by urbanization process, such as good natural environment with less population density, ecological environment with good air quality, promoted hand hygiene, mask wearing, keeping interpersonal distance, vaccination, media publicity for NRIDs' prevention and control.

13.
Article En | MEDLINE | ID: mdl-38740078

PURPOSE: Left ventricular assist devices (LVADs) are well-established for treating end-stage heart failure, but this therapy is only available to Chinese patients in recent years. The CH-VAD is the first used fully magnetically levitated pump and the most widely used device in China. This study reports the long-term outcomes of a cohort supported by the CH-VAD for the first time. METHODS: From June 2017 to August 2023, 50 consecutive patients received CH-VAD implantation in Fuwai Hospital. Clinical data were collected during follow-up and retrospectively analyzed. RESULTS: Baseline characteristics included a mean age of 47.9±13.9 years, 90% male, and 26% ischemic etiology. The INTERMACS profile revealed 12% Profile 1, 56% Profile 2, 26% Profile 3 and 6% Profile 4. Mean support duration was 868 ± 630 days (range 33 days-6.4 years). Kaplan-Meier survival rate was 96% (95% confidence interval [CI], 85 to 99) at 6 months, 93% (95% CI, 79-98) at 1 year, 93% (95% CI, 79-98) at 2 years and 89% (95% CI, 71-96) at 3 years. 40 patients (80%) currently remain on support, 3 were bridged to recovery, 2 received transplant, and 5 expired during support. Major adverse events included right heart failure (10%), surgical related bleeding (8%), arrhythmia (8%) and driveline infection (16%). Major hemocompatibility-related adverse events were limited to 3 non-disabling strokes and 1 gastrointestinal bleeding. There was no major device malfunction during the follow-up period. CONCLUSIONS: The largest single-center experience with the leading LVAD in China shows high survival with low complication rates, demonstrating the CH-VAD is safe and efficient in providing long-term support for end-stage heart failure patients.

14.
Front Psychol ; 15: 1337318, 2024.
Article En | MEDLINE | ID: mdl-38746917

Objective: To investigate the anxiety levels, sleep quality and potential risk factors of healthcare practitioners involved in the management of COVID-19 patients in a mobile cabin hospital, and further to assess the impact of progressive muscle relaxation (PMR) on their anxiety levels and sleep quality. Methods: We conducted a pre-post self-controlled trial. Healthcare practitioners meeting the inclusion criteria underwent daily 30-min PMR sessions for seven consecutive days. The Pittsburgh Sleep Quality Index (PSQI) and Hamilton Anxiety Scale (HAMA) were used to assess the anxiety and sleep quality of subjects pre- and post-intervention. Statistical analysis was performed using the Wilcoxon test, Mann-Whitney U test, Kruskal-Wallis H test, and Spearman rank correlation. Results: A total of 94 participants completed the study. No statistically significant differences in HAMA or PSQI total scores were observed between groups categorized based on demographic variables such as age, sex, and years of education (p > 0.05). The PSQI total score and its components (excluding sleep medication usage) exhibited a positive correlation with the HAMA total score and its psychological anxiety component (p < 0.05), and a correlation was observed between somatic anxiety manifestations and several components of the PSQI. The PSQI total scores before and after intervention were 10.0 (8.0, 13.0) and 8.0 (6.0, 9.0) respectively (p < 0.001); the HAMA total scores were 8.0 (5.0, 13.0) and 6.0 (4.0, 9.5) respectively (p < 0.001). The detection rates of poor sleep and anxiety states, along with their severity, significantly decreased post-intervention (p < 0.001). Conclusion: Healthcare practitioners experience prominent anxiety and sleep issues in the mobile cabin hospital. PMR can be an effective intervention for improving the anxiety and sleep quality of healthcare professionals during support periods in the mobile cabin hospital. However, trials with larger samples are necessitated to further affirm these preliminary findings.

15.
Br J Dermatol ; 2024 May 16.
Article En | MEDLINE | ID: mdl-38752329

BACKGROUND: Psoriasis, a T cell-mediated chronic inflammatory skin condition, is characterized by the interaction of T cells with various cell types, forming an inflammatory microenvironment that sustains psoriatic inflammation. The homeostasis of these tissue-resident T cells are supported by fibroblasts, the primary structural cells in the dermis. In psoriasis, there is an increased expression of matrix metalloproteinase 2 (MMP2), mediating the structural alterations of skin tissues and the modulation of inflammation. Additionally, the CD100-PLXNB2 axis is known to enhance psoriasis inflammation via keratinocytes, and CD103 levels are associated with the severity of psoriasis upon relapse. OBJECTIVE: To elucidate the role of fibroblasts and the MMP2/CD100 axis in modulating psoriasis inflammation. METHODS: CD100 expression and function in psoriasis were assessed using immunofluorescence, ELISA, single-cell transcriptome sequencing, cellular interaction analyses, and qRT-PCR. CD8+ T cells from psoriasis patients were isolated using magnetic beads to investigate the regulatory effect of MMP2 on CD100 expression on their membranes. Single-cell transcriptome sequencing, spatial transcriptome sequencing, mimetic timing analysis, immunofluorescence, and flow cytometry were utilized to determine the origin of MMP2 and its impact on CD103+CD8+ T cells. The hypotheses were further validated in vivo using MMP2 and CD100 inhibitors. RESULTS: Soluble CD100 (sCD100) was significantly upregulated in both psoriatic lesions and peripheral blood, amplifying psoriasis inflammation by promoting the production of inflammatory cytokines by keratinocytes, fibroblasts, and endothelial cells through the sCD100-PLXNB2 axis. Fibroblasts with high MMP2 expression (MMP2hi) exacerbate psoriasis symptoms by facilitating CD100 shedding from CD8+ T cell membranes. Additionally, it was demonstrated that fibroblasts enhance the upregulation of the CD8+ T cell residency factor CD103 in co-cultures with CD8+ T cells. Inhibitors targeting MMP2 and CD100 proved effective in reducing inflammation in a model of imiquimod-induced psoriasis. CONCLUSION: Our findings underscore the pivotal role of MMP2hi fibroblasts in the amplification and recurrence of inflammatory responses in psoriasis. These fibroblasts augment psoriasis inflammation through the CD100-PLXNB2 axis by facilitating CD100 shedding on CD8+ T cell membranes and by upregulating CD103, thereby enhancing CD8+ T cell residency.

16.
Biomol Biomed ; 2024 May 15.
Article En | MEDLINE | ID: mdl-38752985

Kirsten Rat Sarcoma viral oncogene homolog (KRAS) is one of the most frequent oncogenes. However, there are limited treatment options due to its intracellular expression. To address this, we developed a novel bispecific T-cell engager (BiTE) antibody targeting HLA-A2/KRAS G12V complex and CD3 (HLA-G12V/CD3 BiTE). We examined its specific binding to tumor cells and T cells, as well as its anti-tumor effects in vivo. HLA-G12V/CD3 BiTE was expressed in Escherichia coli and its binding affinities to CD3 and HLA-A2/KRAS G12V were measured by flow cytometry, along with T-cell activation. In a xenograft pancreatic tumor model, the HLA-G12V/CD3 BiTE's anti-tumor effects were assessed through tumor growth, survival time, and safety. Our results demonstrated specific binding of HLA-G12V/CD3 BiTE to tumor cells with an HLA-A2/KRAS G12V mutation and T cells. The HLA-G12V/CD3 BiTE also activated T-cells in the presence of tumor cells in vitro. HLA-G12V/CD3 BiTE in vivo testing showed delayed tumor growth without severe toxicity to major organs and prolonged mouse survival. This study highlights the potential of constructing BiTEs recognizing an HLA-peptide complex and providing a novel therapy for cancer treatment targeting the intracellular tumor antigen.

17.
BMC Public Health ; 24(1): 1252, 2024 May 14.
Article En | MEDLINE | ID: mdl-38741086

BACKGROUND: As the number of elderly migrants in China continues to grow, it is necessary to pay closer attention to their health and health services. Some studies have confirmed that social capital plays a significant role in the utilization of health services. Therefore, an in-depth exploration of the relationship between social capital and the utilization of essential public health services (EPHS) by elderly migrants will not only contribute to improving their overall health but also facilitate a more balanced development of public health service system in China. METHODS: Based on the cross-sectional data from the 2017 China Migrants Dynamic Survey (CMDS), this study examined the impact of social capital on the utilization of EPHS among elderly migrants. We evaluated social capital at two distinct levels: the individual and the community, and considered two dimensions of social capital: structural social capital (SSC) and cognitive social capital (CSC). The study aimed to delve into the impact of these forms of social capital on the utilization of EPHS among elderly migrants, and whether the migration range moderates this impact by multilevel logistic regression analysis. RESULTS: A total of 5,728 migrant elderly individuals were selected. The health records establishment rate and health education acceptance rate were approximately 33.0% and 58.6%, respectively. Social capital influenceed the utilization of EPHS among elderly migrants. Specifically, individual-level SSC and CSC have impacts on both the establishment of health records (OR = 1.598, 95%CI 1.366-1.869; OR = 1.705, 95%CI 1.433-2.028) and the acceptance of health education (OR = 1.345, 95%CI 1.154-1.567; OR = 2.297, 95%CI 1.906-2.768) among elderly migrants, while community-level SSC only affected the acceptance of health education (OR = 3.838, 95%CI 1.328-11.097). There were significant differences in individual-level SSC, health records, and health education among different migration range subgroups among elderly migrants. Migration range moderated the effect of social capital on the utilization of EPHS, crossing provinces could weaken the relationship between SSC and health education. CONCLUSIONS: Social capital is associated with a higher utilization rate of EPHS among elderly migrants. It is necessary to encourage them to actively participate in social activities, strengthen public services and infrastructure construction in the area, and improve their sense of belonging and identity.


Social Capital , Transients and Migrants , Humans , China , Male , Aged , Female , Transients and Migrants/statistics & numerical data , Transients and Migrants/psychology , Cross-Sectional Studies , Middle Aged , Logistic Models , Surveys and Questionnaires , Patient Acceptance of Health Care/statistics & numerical data , Aged, 80 and over
18.
Vaccine ; 2024 May 22.
Article En | MEDLINE | ID: mdl-38777696

PURPOSE: To evaluate the impact of momentary intervention on the willingness and actual uptake of influenza vaccination among the elderly in China. METHODS: A cross-sectional study assessed the willingness of the elderly to receive influenza vaccination, and an momentary intervention aimed to increase vaccination willingness among those initially unwilling. The elderly reporting a willingness were offered free influenza vaccination through a community intervention program. RESULTS: A total of 3138 participants were recruited in this study, and 61.3 % (95 % CI 59.6 %-63.0 %) were willing to receive influenza vaccination at baseline. The willingness rate of influenza vaccination increased to 79.8 % (95 % CI 78.4 %-81.2 %), with an increase of 18.5 % (95 % CI 16.3 %-20.7 %) after momentary intervention. The influenza vaccination rate was 40.4 % (95 % CI 38.5 %-42.3 %) before and 53.9 % (95 % CI 52.0 %-55.8 %) after momentary intervention with an increase of 13.5 % (95 % CI 10.9 %-16.2 %). There was no significant difference in influenza vaccination rates between the initially willing people and those who changed to be willing to receive influenza vaccination after momentary intervention (vaccination rates: 78.0 % vs. 81.3 %). CONCLUSION: Momentary intervention has been shown to effectively enhance the willingness of the elderly to receive influenza vaccination, thereby facilitating the translation of this intention into actual behavior.

19.
Sci Bull (Beijing) ; 2024 Apr 28.
Article En | MEDLINE | ID: mdl-38735789

The microdomains of plasmodesmata, specialized cell-wall channels responsible for communications between neighboring cells, are composed of various plasmodesmata-located proteins (PDLPs) and lipids. Here, we found that, among all PDLP or homologous proteins in Arabidopsis thaliana genome, PDLP5 and PDLP7 possessed a C-terminal sphingolipid-binding motif, with the latter being the only member that was significantly upregulated upon turnip mosaic virus and cucumber mosaic virus infections. pdlp7 mutant plants exhibited significantly reduced callose deposition, larger plasmodesmata diameters, and faster viral transmission. These plants exhibited increased glucosidase activity but no change in callose synthase activity. PDLP7 interacted specifically with glucan endo-1,3-ß-glucosidase 10 (BG10). Consistently, higher levels of callose deposition and slower virus transmission in bg10 mutants were observed. The interaction between PDLP7 and BG10 was found to depend on the presence of the Gnk2-homologous 1 (GnK2-1) domain at the N terminus of PDLP7 with Asp-35, Cys-42, Gln-44, and Leu-116 being essential. In vitro supplementation of callose was able to change the conformation of the GnK2-1 domain. Our data suggest that the GnK2-1 domain of PDLP7, in conjunction with callose and BG10, plays a key role in plasmodesmata opening and closure, which is necessary for intercellular movement of various molecules.

20.
Small Methods ; : e2400273, 2024 May 11.
Article En | MEDLINE | ID: mdl-38733258

Chronic wounds pose a significant clinical challenge worldwide, which is characterized by impaired tissue regeneration and excessive scar formation due to over-repair. Most studies have focused on developing wound repair materials that either facilitate the healing process or control hyperplastic scars caused by over-repair, respectively. However, there are limited reports on wound materials that can both promote wound healing and prevent scar hyperplasia at the same time. In this study, VR23-loaded dendritic mesoporous bioglass nanoparticles (dMBG) are synthesized and electrospun in poly(ester-curcumin-urethane)urea (PECUU) random composite nanofibers (PCVM) through the synergistic effects of physical adsorption, hydrogen bond, and electrospinning. The physicochemical characterization reveals that PCVM presented matched mechanical properties, suitable porosity, and wettability, and enabled sustained and temporal release of VR23 and BDC with the degradation of PCVM. In vitro experiments demonstrated that PCVM can modulate the functions and polarization of macrophages under an inflammatory environment, and possess effective anti-scarring potential and reliable cytocompatibility. Animal studies further confirmed that PCVM can efficiently promote re-epithelialization and angiogenesis and reduce excessive inflammation, thereby remarkably accelerating wound healing while preventing potential scarring. These findings suggest that the prepared PCVM holds promise as a bidirectional regulatory dressing for effectively promoting scar-free healing of chronic wounds.

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