Ocular manifestations in ANCA-associated vasculitis: a comprehensive analysis from Chinese medical centers.

INTRODUCTION: This study aimed to explore ocular manifestations in ANCA-associated vasculitis (AAV), focusing on granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), and microscopic polyangiitis (MPA) and to examine the associations with laboratory parameters and other systemic manifestations. METHODS: This retrospective study reviewed data from 533 AAV patients across two major Chinese medical centers from January 2016 to November 2023. Data including diagnosis, cranial manifestations of disease, ocular complications, and laboratory parameters were analyzed. Univariate and multivariable logistic regression analyses assessed associations across disease manifestations. Machine learning models were also utilized to predict the risk of retinal/eye involvement in AAV patients. RESULTS: Among 533 patients (210 GPA, 217 MPA, 99 EGPA, and 7 unclassified AAV), ocular complications were observed in 20.64% of them, with a distribution of 36.67% in GPA, 7.37% in MPA, and 18.18% in EGPA. The most common ocular manifestations included scleritis and retro-orbital mass/dacryocystitis, which were notably prevalent in GPA patients. Retinal involvement was observed in 9.09% of EGPA cases. The machine learning models yielded that eosinophil percentage (EOS%), high-sensitivity C-reactive protein (hsCRP), and CD4 + T cell/CD8 + T cell ratio (T4/T8) can predict retinal involvement. Furthermore, the white blood cell, EOS%, APTT, IgA, hsCRP, PR3-ANCA, and T4/T8 can predict eye involvement. CONCLUSION: Ocular manifestations are a prevalent complication across all forms of AAV. Predictive models developed through machine learning offer promising tools for early intervention and tailored patient care. This necessitates a multidisciplinary approach, integrating rheumatology and ophthalmology expertise for optimal patient outcomes.

New findings on retinal microvascular changes in patients with primary COVID-19 infection: a longitudinal study.

Purpose: To investigate the longitudinal alterations of retinal microvasculature in patients with primary coronavirus disease 2019 (COVID-19) infection. Methods: A cohort of participants, who had never been infected with COVID-19, was recruited between December 2022 and May 2023 at Peking Union Medical College Hospital in Beijing, China. Participants underwent comprehensive ophthalmologic examinations and fundus imaging, which included color fundus photography, autofluorescence photography, swept-source optical coherence tomography (SS-OCT) and SS-OCT angiography (SS-OCTA). If participants were infected with COVID-19 during the study, follow-ups with consistent imaging modality were conducted within one week and two months after recovery from the infection. Results: 31 patients (61 eyes), with a mean age of 31.0 ± 7.2 years old, were eligible for this study. All participants contracted mild COVID-19 infection within one month of baseline data collection. The average period was 10.9 ± 2.0 days post-infection for the first follow-up and 61.0 ± 3.5 days for the second follow-up. No clinical retinal microvasculopathy features were observed during the follow-ups. However, SS-OCTA analysis showed a significant increase in macular vessel density (MVD) from 60.76 ± 2.88% at baseline to 61.59 ± 3.72%(p=0.015) at the first follow-up, which subsequently returned to the baseline level of 60.23 ± 3.33% (p=0.162) at the two-month follow-up. The foveal avascular zone (FAZ) remained stable during the follow-ups with areas of 0.339 ± 0.097mm2, 0.342 ± 0.093mm2, and 0.344 ± 0.098mm2 at the baseline, first follow-up (p=0.09) and second follow-up (p=0.052), respectively. Central macular thickness, cube volume and ganglion cell-inner plexiform layer showed a transient decrease at the first follow-up(p<0.001, p=0.039, p=0.002, respectively), and increased to baseline level at the two-month follow-up(p=0.401, p=0.368, p=0.438, respectively). Conclusion: Mild COVID-19 infection may temporarily and reversibly impact retinal microvasculature, characterized by a transient increase in retinal blood flow during the early recovery phase, which returns to the pre-infection level two months post-infection.

eDNA Metabarcoding Reveals the Species-Area Relationship of Amphibians on the Zhoushan Archipelago.

The species-area relationship is important for understanding species diversity patterns at spatial scales, but few studies have examined the relationship using environmental DNA (eDNA) techniques. We investigated amphibian diversity on 21 islands of the Zhoushan Archipelago and nearby mainland areas in China using the combination of eDNA metabarcoding and the traditional line transect method (TLTM) and identified the species-area relationship for amphibians on the islands. The mean detection probability of eDNA is 0.54, while the mean detection probability of TLTM is 0.24. The eDNA metabarcoding detected eight amphibian species on the islands and nine species in the mainland areas, compared with seven species on the islands and nine species in the mainland areas that were identified by TLTM. Amphibian richness on the islands increased with island area and habitat diversity. The species-area relationship for amphibians in the archipelago was formulated as the power function (S = 0.47A0.21) or exponential function (S = 2.59 + 2.41 (logA)). Our results suggested that eDNA metabarcoding is more sensitive for the detection of amphibian species. The combined use of eDNA metabarcoding and the traditional line transect method may optimize the survey results for amphibians.

Longitudinal validation of cognitive reserve proxy measures: a cohort study in a rural Chinese community.

BACKGROUND: While evidence supports cognitive reserve (CR) in preserving cognitive function, longitudinal validation of CR proxies, including later-life factors, remains scarce. This study aims to validate CR's stability over time and its relation to cognitive function in rural Chinese older adults. METHODS: Within the project on the health status of rural older adults (HSRO), the survey included baseline assessment (2019) and follow-up assessment (2022). 792 older adults (mean age: 70.23 years) were followed up. The confirmatory factor analysis (CFA) was constructed using cognitive reserve proxies that included years of formal education, social support, hobbies, and exercise. We examined the longitudinal validity of the CR factor using confirmatory factor analyses and measurement invariance and explored the association of CR with cognition using Spearman's correlation and Generalized Estimating Equations (GEE). RESULTS: The results showed that CR's CFA structure was stable over time (T0, χ2/df: 3.21/2; RMSEA: 0.02, and T1, χ2/df: 7.47/2; RMSEA: 0.05) and that it accepted both configural and metric invariance (Δχ2/df = 2.28/3, P = 0.52). In addition, it was found that CR had a stable positive relationship with cognitive function across time (T0, r = 0.54; T1, r = 0.49). Furthermore, longitudinal CR were associated with MMSE (ß = 2.25; 95%CI = 2.01 ~ 2.49). CONCLUSIONS: This study provided valuable evidence on the stability and validity of cognitive reserve proxy measures in rural Chinese older adults. Our findings suggested that cognitive reserve is associated with cognitive function over time and highlighted the importance of accumulating cognitive reserve in later life.

The responses of CO2 emission to nitrogen application and earthworm addition in the soybean cropland.

The effects of nitrogen application or earthworms on soil respiration in the Huang-Huai-Hai Plain of China have received increasing attention. However, the response of soil carbon dioxide (CO2) emission to nitrogen application and earthworm addition is still unclear. A field experiment with nitrogen application frequency and earthworm addition was conducted in the Huang-Huai-Hai Plain. Results showed nitrogen application frequency had a significant effect on soil respiration, but neither earthworms nor their interaction with nitrogen application frequency were significant. Low-frequency nitrogen application (NL) significantly increased soil respiration by 25%, while high-frequency nitrogen application (NH), earthworm addition (E), earthworm and high-frequency nitrogen application (E*NH), and earthworm and low-frequency nitrogen application (E*NL) also increased soil respiration by 21%, 21%, 12%, and 11%, respectively. The main reason for the rise in soil respiration was alterations in the bacterial richness and keystone taxa (Myxococcales). The NH resulted in higher soil nitrogen levels compared to NL, but NL had the highest bacterial richness. The abundance of Corynebacteriales and Gammaproteobacteria were positively connected with the CO2 emissions, while Myxococcales, Thermoleophilia, and Verrucomicrobia were negatively correlated. Our findings indicate the ecological importance of bacterial communities in regulating the carbon cycle in the Huang-Huai-Hai Plain.

CD93 regulates breast cancer growth and vasculogenic mimicry through the PI3K/AKT/SP2 signaling pathway activated by integrin ß1.

In women, breast cancer (BC) accounts for 7%-10% of all cancer cases and is one of the most common cancers. To identify a new method for treating BC, the role of CD93 and its underlying mechanism were explored. MDA-MB-231 cells were used in this study and transfected with si-CD93, si-MMRN2, oe-CD93, si-integrin ß1, or oe-SP2 lentivirus. After MDA-MB-231 cells were transfected with si-NC or si-CD93, they were injected into nude mice by subcutaneous injection at a dose of 5 × 106/mouse to construct a BC animal model. The expression of genes and proteins and cell migration, invasion and vasculogenic mimicry were detected by RT‒qPCR, western blot, immunohistochemistry, immunofluorescence, Transwell, and angiogenesis assays. In pathological samples and BC cell lines, CD93 was highly expressed. Functionally, CD93 promoted the proliferation, migration, and vasculogenic mimicry of MDA-MB-231 cells. Moreover, CD93 interacts with MMRN2 and integrin ß1. Knockdown of CD93 and MMRN2 can inhibit the activation of integrin ß1, thereby inhibiting the PI3K/AKT/SP2 signaling pathway and inhibiting BC growth and vasculogenic mimicry. In conclusion, the binding of CD93 to MMRN2 can activate integrin ß1, thereby activating the PI3K/AKT/SP2 signaling pathway and subsequently promoting BC growth and vasculogenic mimicry.

FOXA1-Driven pathways exacerbate Radiotherapy-Induced kidney injury in colorectal cancer.

OBJECTIVE: This study aimed to investigate the role of FOXA1 in acute kidney injury (AKI) induced by radiotherapy in colorectal cancer. Although FOXA1 is known to be aberrantly expressed in malignant tumors, its contribution to AKI remains unclear. This study aimed to explore the involvement of FOXA1 in AKI induced by radiotherapy in colorectal cancer and its influence on the regulation of downstream target genes. METHODS: Firstly, a transcriptome analysis was performed on mice to establish a radiation-induced AKI model, and qPCR was used to determine the expression of FOXA1 in renal cell injury models induced by X-ray irradiation. Additionally, FOXA1 was silenced using lentiviral vectors to investigate its effects on the apoptosis of mice with radiation-induced AKI and HK-2 cells. Next, bioinformatics analysis and various experimental validation methods such as ChIP assays, co-immunoprecipitation, and dual-luciferase reporter assays were employed to explore the relationship between FOXA1 and the downstream regulatory factors ITCH promoter and the ubiquitin ligase-degradable TXNIP. Finally, lentiviral overexpression or knockout techniques were used to investigate the impact of the FOXA1/ITCH/TXNIP axis on oxidative stress and the activation of inflammatory body NLRP3. RESULTS: This study revealed that FOXA1 was significantly upregulated in the renal tissues of mice with radiation-induced AKI and in the injured HK-2 cells. Furthermore, in vitro cell experiments and animal experiments demonstrated that FOXA1 suppressed the transcription of the E3 ubiquitin ligase ITCH, thereby promoting apoptosis of renal tubular cells and causing renal tissue damage. Further in vivo animal experiments confirmed that TXNIP, a protein degraded by ITCH ubiquitination, could inhibit oxidative stress and the activation of NLRP3 inflammasome in the AKI mouse model. CONCLUSION: FOXA1 enhances oxidative stress, cell apoptosis, and NLRP3 inflammasome activation by regulating the ITCH/TXNIP axis, thereby exacerbating radiotherapy-induced AKI.

Systemic risk factors of retinopathy in patients with systemic lupus erythematosus.

OBJECTIVE: To investigate the risk factors of lupus retinopathy (LR) in patients with systemic lupus erythematosus (SLE). METHODS: This is a retrospective, cross-sectional study. LR patients admitted at Peking Union Medical College Hospital from June 2013 to April 2023 were reviewed. Age- and gender-matched SLE patients without retinopathy were selected as controls. Medical records including clinical manifestations, laboratory data and ophthalmic examination were collected. Univariate and multivariate logistic regression analyses were conducted. RESULTS: One hundred and twelve LR patients (198 eyes) were included, with 12 cases (14 eyes) presenting with retinal macrovascular obstruction, and 100 cases (184 eyes) only exhibiting microvasculopathy. Multivariate analysis indicated the presence of haemolytic anaemia, decreased haemoglobin (HGB) and higher relative percentage of neutrophils were independent risk factors for LR (p < 0.05). The first two were also risk factors for retinal microvasculopathy, whereas secondary antiphospholipid syndrome (APS) was for macrovascular obstruction. In male group, LR had significant associations with decreased HGB, no matter which types of retinopathy (p < 0.05). In female group, LR was significantly associated with haemolytic anaemia, presence of antiphospholipid antibodies, decreased white blood cells and relative high percentage of neutrophils. Specifically, haemolytic anaemia (p = 0.002) was significantly associated with retinal microvasculopathy, and APS (p = 0.003) was significantly associated with macrovasculature obstruction. CONCLUSION: LR was related to haemolytic anaemia, decreased HGB levels and higher percentage of neutrophils. Retinal microvasculopathy accounted for most cases and macrovasculature obstructions were rare. Male and female patients have distinct risk factors. Early ophthalmic screening is recommended especially for those with risk factors of LR.

ACETYL-COA PRODUCTION BY OCTANOIC ACID ALLEVIATES ACUTE COMPARTMENT SYNDROME-INDUCED SKELETAL MUSCLE INJURY THROUGH REGULATING MITOPHAGY.

ABSTRACT: Background: Treatment of acute compartment syndrome (ACS)-induced skeletal muscle injury remains a challenge. Previous studies have shown that octanoic acid is a promising treatment for ACS owing to its potential ability to regulate metabolic/epigenetic pathways in ischemic injury. The present study was designed to investigate the efficacy and underlying mechanism of octanoic acid in ACS-induced skeletal muscle injury. Methods: In this study, we established a saline infusion ACS rat model. Subsequently, we assessed the protective effects of sodium octanoate (NaO, sodium salt of octanoic acid) on ACS-induced skeletal muscle injury. Afterward, the level of acetyl-coenzyme A and histone acetylation in the skeletal muscle tissue were quantified. Moreover, we investigated the activation of the AMP-activated protein kinas pathway and the occurrence of mitophagy in the skeletal muscle tissue. Lastly, we scrutinized the expression of proteins associated with mitochondrial dynamics in the skeletal muscle tissue. Results: The administration of NaO attenuated muscle inflammation, alleviating oxidative stress and muscle edema. Moreover, NaO treatment enhanced muscle blood perfusion, leading to the inhibition of apoptosis-related skeletal muscle cell death after ACS. In addition, NaO demonstrated the ability to halt skeletal muscle fibrosis and enhance the functional recovery of muscle post-ACS. Further analysis indicates that NaO treatment increases the acetyl-CoA level in muscle and the process of histone acetylation by acetyl-CoA. Lastly, we found NaO treatment exerts a stimulatory impact on the activation of the AMPK pathway, thus promoting mitophagy and improving mitochondrial dynamics. Conclusion: Our findings indicate that octanoic acid may ameliorate skeletal muscle injury induced by ACS. Its protective effects may be attributed to the promotion of acetyl-CoA synthesis and histone acetylation within the muscular tissue, as well as its activation of the AMPK-related mitophagy pathway.

Quantitative assessment of retinal vasculature changes in systemic lupus erythematosus using wide-field OCTA and the correlation with disease activity.

Purpose: To assess the retinal vasculature changes quantitatively using wide-field optical coherence tomography angiography (OCTA) in systemic lupus erythematosus (SLE), and explore its correlation with systemic clinical features. Design: Prospective, cross-sectional, observational study. Participants and controls: Patients with SLE who presented to the Ophthalmology Department of Peking Union Medical College Hospital from November 2022 to April 2023 were collected. The subjects were divided into retinopathy and without retinopathy groups. Age and gender-matched healthy subjects were selected as controls. Methods: Patients with SLE and control subjects were imaged with 24×20 mm OCTA scans centered on the fovea and 6×6 mm OCTA scans centered on the optic disc. The sub-layers of OCTA images were stratified by the built-in software of the device and then the retinal thickness and vessel density were measured automatically. The characteristics of retinal OCTA parameters of SLE and its correlation with systemic clinical indicators of patients without retinopathy were analyzed. Main outcome measures: OCTA parameters, visual acuity, intraocular pressure, and systemic clinical indicators of patients such as disease activity index, autoimmune antibodies, and inflammatory marker levels were collected. Results: A total of 102 SLE patients were included, 24 of which had retinopathy, and 78 had unaffected retina. Wide-field OCTA could effectively detect retinal vascular obstruction, non-perfusion area, and morphological abnormalities in patients with lupus retinopathy. SLE patients without retinopathy had significantly higher retinal superficial vessel density (SVD) in foveal (P=0.02), para-foveal temporal (P=0.01), nasal (P=0.01), peripheral foveal temporal (P=0.02), and inferior areas (P=0.02), as well as subregion temporal (P=0.01) and inferior areas (P=0.03) when compared with healthy controls (n=65 eyes from 65 participants). The area under curve (AUC) value of subregion inferior SVD combined parafoveal temporal SVD was up to 0.70. There was a significantly positive correlation between SVD and disease activity in SLE without retinopathy group. Patients with severe activity had the most significant increase in SVD. Conclusion: Wide-field OCTA can provide a relatively comprehensive assessment of the retinal vasculature in SLE. In the absence of pathological changes of the retina, the SVD was significantly increased and was positively correlated with the disease activity of SLE.

Association of Cardiac Biomarkers in Combination With Cognitive Impairment After Acute Ischemic Stroke.

BACKGROUND: Poststroke cognitive impairment is a severe and common clinical complication that constitutes a substantial global health burden. We aimed to evaluate the association of 3 cardiac biomarkers in combination with poststroke cognitive impairment and their prognostic significance. METHODS AND RESULTS: This prospective study included 566 patients with ischemic stroke. Cardiac biomarkers, including sST2 (soluble suppression of tumorigenicity-2 receptor), GDF-15 (growth differentiation factor-15), and NT-proBNP (N-terminal pro-B-type natriuretic peptide), were measured. Cognitive impairment was defined as a Mini-Mental State Examination score of <27 or a Montreal Cognitive Assessment score of <25 at 3 months after ischemic stroke. Odds of cognitive impairment 3 months after ischemic stroke increased with the number of elevated cardiac biomarkers (sST2, GDF-15, and NT-proBNP; Ptrend<0.001). The multivariable adjusted odds ratios (95% CIs) of cognitive impairment defined by the Mini-Mental State Examination and Montreal Cognitive Assessment were 2.45 (1.48-4.07) and 1.86 (1.10-3.14) for the participants with ≥2 elevated cardiac biomarkers, respectively, compared with those without any elevated cardiac biomarker. Additionally, higher cardiac biomarker scores were associated with an increased risk of cognitive impairment (Ptrend<0.05). Simultaneously adding all 3 cardiac biomarkers to the basic model with traditional risk factors significantly improved the risk prediction of Mini-Mental State Examination-defined cognitive impairment (net reclassification improvement=34.99%, P<0.001; integrated discrimination index=2.67%, P<0.001). Similar findings were observed using the Montreal Cognitive Assessment scores. CONCLUSIONS: An increased number of elevated novel cardiac biomarkers were associated with an increased odds of poststroke cognitive impairment, suggesting that a combination of these cardiac biomarkers may improve the risk prediction of cognitive impairment. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01840072.

Differences between young and elderly polypoidal choroidal vasculopathy patients with and without pachychoroid phenotypes.

PURPOSE: To investigate the distinct characteristics between young and elderly polypoidal choroidal vasculopathy (PCV) patients based on the pachy- or non-pachychoroid phenotypes. METHODS: PCV patients treated with intravitreal injections of Conbercept based on the 3 + PRN regimen from 27 centers of China PCV Research Alliance were included. Patients were categorized into the young and the elderly aged group based on the cut-off point determined using the Youden method according to the pachychoroid phenotypes. The characteristics of past medical history, lifestyle factors, fundus manifestations, and treatment response between the subgroups were analyzed. RESULTS: Three hundred eight eligible patients were included. Multivariate logistic regression showed a significant association between age and PCV subtype classification (OR = 0.921, P = 0.002). A cutoff age of 64.5 effectively distinguished between pachychoroid PCV and non-pachychoroid PCV (P < 0.001). Elderly PCV patients had a higher incidence of hypertension history (P = 0.044) but a lower incidence of diabetes history (P = 0.027). In terms of lifestyle, smoking history (P = 0.015) and staying up late (P = 0.004) were more significant in the young group of PCV patients. For clinical characteristics, the proportion of hemorrhagic PCV in the young group was significantly higher (P = 0.038), with a higher proportion of sharp-peaked PED (P = 0.049), thicker choroid (P < 0.001) but a lower portion of double-layer sign (P = 0.023) in OCT. Both groups showed significant anatomical changes compared to baseline in each follow-up period (P < 0.05), with the young group having a higher proportion of good anatomical response after the first injection (P = 0.009). CONCLUSION: PCV patients stratified by subtype exhibit distinct characteristics between the young and elderly groups.

Evaluation of the First-Dose Anti-VEGF Anatomical Response in Polypoidal Choroidal Vasculopathy Patients: Correlation with the Third-Dose Response and Risk Factor Analysis.

INTRODUCTION: The aims of the study were to investigate whether first-dose efficacy can predict third-dose anatomical response and analyze the risk factors for first-dose response of polypoidal choroidal vasculopathy (PCV) patients. METHODS: We retrospectively reviewed patients' medical records from 27 centers of China PCV Research Alliance. PCV patients treated with intravitreal injections of conbercept (IVC) based on the 3+ pro re nata regimen (three initial monthly injections, followed by injections as needed) with complete 3-month injection data were included. Response correlations, risk factor associations, changes in central macular thickness (CMT) or best-corrected visual acuity (BCVA), and number of injections in the first year of follow-up were evaluated separately in the pachy-PCV and non-pachy-PCV phenotypes. RESULTS: Overall, 165 eligible patients were included. There was a significant correlation between first-dose and third-dose anatomical response in pachy-PCV or non-pachy-PCV patients (rs = 0.611, p < 0.001; rs = 0.638, p < 0.001). Multivariate analysis revealed associations of good first-dose anatomical response in pachy-PCV patients with baseline CMT with a predicted area under the curve (AUC) of 0.847, while a good response in non-pachy-PCV patients was associated with baseline BCVA, baseline CMT, pigment epithelial detachment (PED) height, higher proportion of intraretinal fluid, and lower PED minimum diameter with a predicted AUC of 0.940. CMT in the good first-dose response group was significantly decreased from baseline at all first-year follow-up visits in both groups (p < 0.001), and mean BCVA was improved in the good versus poor first-dose anatomical response group (5.4 vs. 1.6 ETDRS letters in pachy-PCV, 10.6 vs. 7.4 letters in non-pachy-PCV) after the third injection. No significant difference was observed in the number of injections in the first year of follow-up between different response groups. CONCLUSION: In PCV patients receiving IVC, the first- and third-dose responses are significantly correlated, and different factors influence the first-dose response in different subtypes of PCV.

Low levels of free triiodothyronine are associated with risk of cognitive impairment in older euthyroid adults.

Accumulated evidence showed that thyroid diseases induced cognitive decline. However, the relationship between thyroid hormones (THs) and cognition in older euthyroid people is still unclear. Our study aimed to estimate the association between THs within the euthyroid range and cognition in community-dwelling older adults in China. Data were extracted from a cohort study on the health status of rural older adults from the Guizhou province in China (HSRO). Serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were measured using the electrochemiluminescence immunoassay. Cognitive function was evaluated by the Mini-Mental State Examination (MMSE). Linear regression and a binary logistic regression model were used to explore the relationship between THs and cognition in euthyroidism (TSH level of 0.27 ~ 4.20mIU/L). A total of 957 euthyroidism individuals were included in this study, with a mean (SD) age of 71.34 (6.35) years. In individuals with euthyroidism, serum TSH and FT3 levels were positively associated with cognition (TSH:ß = 0.06, 95% CI 0.01 ~ 0.11, P = 0.03; FT3:ß = 0.07, 95% CI 0.01 ~ 0.12, P = 0.01); and serum FT3 and TSH levels were significantly associated with cognitive domains (P < 0.05). Further, euthyroid individuals in the lowest serum FT3(OR = 1.96; 95% CI 1.27 ~ 3.03) quartile had a twofold increased risk of cognitive impairment compared to those in the highest quartile after adjusting for potential confounding factors. These findings suggested that low levels of FT3 could be an independent risk factor for cognitive impairment in older euthyroid adults. Additionally, a positive linear association exists between serum FT3 levels and cognitive domains (such as immediate memory, language, and attention). Further studies are needed to determine the underlying mechanisms and the community significance of these findings.

Relationship between mental health literacy and professional psychological help-seeking attitudes in China: a chain mediation model.

BACKGROUND: Mental health literacy is considered an important factor in promoting professional psychological help-seeking attitudes. However, it is important to clarify the emotional and behavioral factors that underlie this association. Drawing from the ABC model of attitudes and the Health Disclosure Decision-Making Model, this study aimed to examine the mediating role of psychological help-seeking stigma and distress disclosure in the relationship between mental health literacy and professional psychological help-seeking attitudes. METHODS: We collected data from 827 participants in seven regions of China (597 female; Mage = 26.019, SD = 5.592 years old) using self-report measures, including the Mental Health Literacy Scale, Questionnaire of Stigma for Seeking Professional Psychological Help, Distress Disclosure Index, and Attitudes Toward Seeking Professional Psychological Help-Short Form. A chain mediation model was built to examine the relationships among mental health literacy, psychological help-seeking stigma, distress disclosure, and professional psychological help-seeking attitudes. RESULTS: The results of the analyses showed a positive association between mental health literacy and professional psychological help-seeking attitudes, with psychological help-seeking stigma and distress disclosure playing mediating roles in this relationship. Furthermore, even after controlling for participants' age, gender, and education, the chain mediation effect of psychological help-seeking stigma and distress disclosure on the relationship between mental health literacy and professional psychological help-seeking attitudes was observed among the Chinese population. CONCLUSIONS: These findings underscore the significance of mental health literacy in shaping professional psychological help-seeking attitudes, while emphasizing the need to account for psychological help-seeking stigma and distress disclosure when examining this association. Additionally, the model proposed in this study provides a valuable framework for promoting the utilization of professional mental health services.

Extracellular vesicles derived from human ESC-MSCs target macrophage and promote anti-inflammation process, angiogenesis, and functional recovery in ACS-induced severe skeletal muscle injury.

BACKGROUND: Acute compartment syndrome (ACS) is one of the most common complications of musculoskeletal injury, leading to the necrosis and demise of skeletal muscle cells. Our previous study showed that embryonic stem cells-derived mesenchymal stem cells (ESC-MSCs) are novel therapeutics in ACS treatment. As extracellular vesicles (EVs) are rapidly gaining attention as cell-free therapeutics that have advantages over parental stem cells, the therapeutic potential and mechanisms of EVs from ESC-MSCs on ACS need to be explored. METHOD: In the present study, we examined the protective effects in the experimental ACS rat model and investigated the role of macrophages in mediating these effects. Next, we used transcriptome sequencing to explore the mechanisms by which ESC-MSC-EVs regulate macrophage polarization. Furthermore, miRNA sequencing was performed on ESC-MSC-EVs to identify miRNA candidates associated with macrophage polarization. RESULTS: We found that intravenous administration of ESC-MSC-EVs, given at the time of fasciotomy, significantly promotes the anti-inflammation process, angiogenesis, and functional recovery of muscle in ACS. The beneficial effects were associated with ESC-MSC-EVs affecting macrophage polarization by delivering various miRNAs which regulate NF-κB, JAK/STAT, and PI3K/AKT pathways. Our data further illustrate that ESC-MSC-EVs mainly modulate macrophage polarization via the miR-21/PTEN, miR-320a/PTEN, miR-423/NLRP3, miR-100/mTOR, and miR-26a/TLR3 axes. CONCLUSION: Together, our results demonstrated the beneficial effects of ESC-MSC-EVs in ACS, wherein the miRNAs present in ESC-MSC-EVs regulate the polarization of macrophages.

Diradicaloid Boron-Doped Molecular Carbons Achieved by Pentagon-Fusion.

Molecular carbons (MCs) are molecular cutouts of carbon materials. Doping with heteroatoms and constructing open-shell structures are two powerful approaches to achieve unexpected and unique properties of MCs. Herein, we disclose a new strategy to design open-shell boron-doped MCs (BMCs), namely by pentagon-fusion of an organoborane π-system. We synthesized two diradicaloid BMC molecules that feature C24 B and C38 B π-skeletons containing a pentagonal ring. A thorough investigation reveals that such pentagon-fusion not only leads to their local antiaromaticity, but also incorporates an internal quinoidal substructure and thereby induces open-shell singlet diradical states. Moreover, their fully fused structures enable efficient π conjugation, which is expanded over the whole frameworks. Consequently, some intriguing physical properties are achieved, such as narrow energy gaps, very broad light absorptions, and superior photothermal capability, along with excellent photostability. Notably, the solid of the C38 B molecule exhibits absorption that covers the range of 300-1200 nm and an efficiency of 93.5 % for solar-driven water evaporation, thus demonstrating the potential of diradicaloid BMCs as high-performance organic photothermal materials.

Structures of the holoenzyme TglHI required for 3-thiaglutamate biosynthesis.

Structural diverse natural products like ribosomally synthesized and posttranslationally modified peptides (RiPPs) display a wide range of biological activities. Currently, the mechanism of an uncommon reaction step during the biosynthesis of 3-thiaglutamate (3-thiaGlu) is poorly understood. The removal of the ß-carbon from the Cys in the TglA-Cys peptide catalyzed by the TglHI holoenzyme remains elusive. Here, we present three crystal structures of TglHI complexes with and without bound iron, which reveal that the catalytic pocket is formed by the interaction of TglH-TglI and that its activation is conformation dependent. Biochemical assays suggest a minimum of two iron ions in the active cluster, and we identify the position of a third iron site. Collectively, our study offers insights into the activation and catalysis mechanisms of the non-heme dioxygen-dependent holoenzyme TglHI. Additionally, it highlights the evolutionary and structural conservation in the DUF692 family of biosynthetic enzymes that produce diverse RiPPs.

THERAPEUTIC EFFECT OF USING AUTOLOGOUS PLATELET CONCENTRATE IN VITRECTOMY FOR MACULAR HOLE: A Systematic Review and Meta-Analysis.

PURPOSE: To summarize the current evidence regarding the therapeutic effect of using autologous platelet concentrate (APC) in vitrectomy for macular hole (MH). METHODS: The PubMed, Web of Science, and Embase databases were searched according to the PROSPERO protocol (CRD42022366202). Controlled trials comparing whether APC was used in the vitrectomy of MH were included. The primary outcome was the closure rate of MH and postoperative best-corrected visual acuity, and the secondary outcome was the incidence of different types of complications. RESULTS: Seven studies that included 634 eyes were eligible. For the primary outcome, the usage of APC significantly improved the closure rate of MH in vitrectomy (odds ratio [OR] = 5.34, 95% confidence interval, 2.83-10.07, P < 0.001). Postoperative visual acuity did not significantly differ between the APC group and similar baseline controls (SMD = -0.07, 95% confidence interval, -0.35 to 0.22, P = 0.644). For the secondary outcome, using APC did not result in additional complications regarding postoperative retinal detachment or the recurrence of MH. CONCLUSION: The use of APC in vitrectomy was associated with a superior closure rate of the hole and no additional complications; therefore, it is effective and safe in MH surgery.

Constructing of predictive model for the surgical effect of patients with cleft lip and palate.

OBJECTIVE: To explore effective factors of surgical effect for patients with cleft lip and palate, and to construct the predictive model of surgical effect, which provide reference for improving the effect of cleft lip and palate surgery. METHODS: This study has been ethically reviewed and approved by the Medical Ethics Committee of Guiyang Stomatological Hospital before the study began.A total of 997 cases of cleft lip and palate surgical treatment in Guiyang Stomatological Hospital from 2015 to 2020 were collected. Logistic regression analysis was used to analyze the factors influencing the surgical outcome, and a score system was established by assigning values to the influencing factors using the nomogram. Data of 110 patients were verified, and decision curve analysis was used to evaluate the predicted results. RESULTS: Logistic regression analysis showed that the number of surgeries, surgical methods, breast milk, prenatal examination, nutrition during pregnancy and labor intensity during pregnancy were independent risk factors for poor surgical results (all P<0.05). The predictive model was built by including the number of surgeries, surgical methods, breast milk, prenatal examination, nutrition and labor intensity during pregnancy into the predictive scoring system. The critical value was 273, the area under ROC curve (AUC) was 0.733(95%CI:0.704~0.76), the sensitivity was 89.57%, and the specificity was 48.14%.When the external validation data of 110 patients were brought into the score, the AUC of poor diagnostic value reached 74.5%, P<0.05, which was close to the modeling accuracy of 73.3%. CONCLUSION: This study constructed a predictive model of surgical effect for patients with cleft lip and palate, which can be used for the clinical prediction of cleft lip and palate patients in Guizhou Province.