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"Xu, Hongbo"
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Mesenchymal Stem Cell Derived Exosomes Therapy in Diabetic Wound Repair
by
Li, Hongjie
,
Xu, Hongbo
,
Jing, Shengyu
in
Biological products
,
biomaterial
,
Care and treatment
2023
Nowadays, refractory diabetic wounds cause a worldwide medical burden. Mesenchymal stem cells derived exosomes (MSC-Exos) show promise as a solid alternative to existing therapeutics in the latest researches, since MSC-Exos share similar biologic activity but less immunogenicity when compared with MSCs. To facilitate further understanding and application, it is essential to summarize the current progress and limitations of MSC-Exos in the treatment of diabetic wounds. In this review, we introduce the effects of different MSC-Exos on diabetic wounds according to their origins and contents and discuss the specific experimental conditions, target wound cells/pathways, and specific mechanisms. In addition, this paper focuses on the combination of MSC-Exos and biomaterials, which improves the efficacy and utilization of MSC-Exos therapy. Together, exosome therapy has high clinical value and application prospects, both in its role and in combination with biomaterials, while novel drugs or molecules loaded into exosomes as carriers targeting wound cells will be development trends.
Journal Article
Federated learning via over-the-air computation in IRS-assisted UAV communications
2023
Intelligent reflective surface (IRS) and unmanned aerial vehicle (UAV) communication are two key technologies in the sixth generation of mobile communication (6G). In this paper, IRS is equipped on UAV to form aerial IRS, which can achieve 360° panoramic full-angle reflection and flexible deployment of IRS. In order to achieve high-quality and ubiquitous network coverage under data privacy and low latency requirements, we propose an Federated learning (FL) network via Over-the-Air computation (AirComp) in IRS-assisted UAV communications. Our goal is to minimize the worst-case mean square error (MSE) by jointly optimizing the IRS phase shift, denoising factor for noise suppression, the user’s transmission power, and UAV trajectory. Optimizing and quickly adjusting the UAV position and IRS phase shift, it flexibly assists the signal transmission between users and base stations (BS). In order to solve this complex non-convex problem, we propose a low-complexity iterative algorithm, which divides the original problem into four sub-problems, respectively using the semi-definite programming (SDP) method, slack variable introduction method, successive convex approximation (SCA) method to solve each sub-problem. Through the analysis of simulation results, our proposed design scheme is obviously better than other benchmark schemes.
Journal Article
Identification of novel compound heterozygous variants in the PEX10 gene in a Han-Chinese family with PEX10-related peroxisome biogenesis disorders
2025
The peroxisome biogenesis disorders (PBDs) are a group of rare inherited autosomal recessive diseases characterized by motor and cognitive neurological dysfunction, hypotonia, seizures, feeding difficulties, retinopathy, sensorineural hearing loss, hepatic and renal abnormalities, and chondrodysplasia punctata of long bones, and the clinical expression is variable. Exome sequencing and Sanger sequencing were used to identify the genetic defect for PBDs in a two-generation non-consanguineous Han-Chinese pedigree. Compound heterozygous variants, a novel splicing variant c.113-2A>G and a reported substitution c.890T>C (p.Leu297Pro), in the peroxisomal biogenesis factor 10 gene ( PEX10 ) were detected. The splicing variant c.113-2A>G led to a canonical splice acceptor site inactivation, exon 2 skipping, and in-frame deletions (p.Ala39_Gly65del). The three patients had similar phenotypes of milder PBDs, which were further genetically determined as PBD6B. The findings extend the PEX10 variant spectrum and may provide new insights into PBDs causation and diagnosis, with implications for genetic counseling and clinical management.
Journal Article
Social anxiety and loneliness among older adults: a moderated mediation model
2024
Background
Few studies have clarified the mechanisms linking social anxiety and loneliness in older populations. The study aimed to explore how social network mediate the relationship between social anxiety and loneliness in older adults, with perceived social support playing a moderating role.
Methods
A total of 454 older patients completed the Social Avoidance and Distress Scale, Lubben Social Network Scale-6, Chinese version of the Short Loneliness Scale and Perceived Social Support Scale. Bootstrap and simple slope methods were used to test the moderated mediation model.
Results
Social anxiety had a significant positive predictive effect on loneliness and social network partially mediated this relationship. The relationship between social anxiety and social network, as well as the relationship between social network and loneliness, was moderated by perceived social support. Specifically, perceived social support buffered the effects of social anxiety on social network, but the buffering effect diminished with increasing levels of social anxiety. On the social network and loneliness pathway, the social network of older persons with higher perceived social support has a stronger prediction of loneliness.
Conclusions
The study found that social anxiety can contribute to loneliness by narrowing older adults’ social network. High perceived social support can buffer this process, but do not overstate its protective effects. Thus, interventions to reduce social anxiety and improve social network and social support may help prevent and alleviate loneliness in older adults.
Journal Article
A novel SLC20A2 nonsense variant and mechanistic studies of primary brain calcification
2026
Primary brain calcification (PBC) is a rare neurodegenerative disease featured by bilateral brain calcifications and exhibiting high phenotypic and genetic heterogeneity. The clinical manifestations mainly include movement disorders, cognitive deficits, and neuropsychiatric symptoms. In this study, a novel heterozygous nonsense variant, c.1669C > T [p.(Gln557*)], in the solute carrier family 20 member 2 gene ( SLC20A2 ), encoding type III sodium-dependent inorganic phosphate transporter 2 (PiT2), was identified in a Han-Chinese family with PBC using whole exome sequencing and Sanger sequencing. Bioinformatics analysis predicted the variant’s deleterious effect. The cellular function impacts of the p.Gln557* variant and three other common PBC-related SLC20A2 variants, p.Ser113*, p.Ala585Thr, and p.Ser601Trp, were subsequently revealed. Subcellular localization analysis showed that the PiT2-Q557*, A585T, and S601W mutants mainly distributed in the plasma membrane and cytosol, whereas the PiT2-S113* mutant showed a diffuse distribution throughout the cells. All four investigated variants significantly impaired cellular inorganic phosphate transport activity. The protein mislocalization-inducing p.Ser113* variant likely causes haploinsufficiency, while the p.Gln557*, p.Ala585Thr, and p.Ser601Trp variants may lead to full or partial loss of function, or exert a dominant-negative effect. Cells expressing PiT2 mutants all exhibited inhibited proliferative and migratory activities, along with enhanced apoptosis. These SLC20A2 variants probably impair critical cellular functions, potentially providing an explanation for the neurological symptoms observed in PBC patients. These findings further broaden SLC20A2 variant spectrum and provide valuable mechanistic insights into the pathogenesis of SLC20A2 -associated PBC.
Journal Article
Genetic analysis of LRRK2 variants in Han Chinese patients with Parkinson’s disease
2026
Parkinson’s disease (PD) is the second most common neurodegenerative disorder, with variants in the leucine rich repeat kinase 2 gene ( LRRK2 ) being frequent genetic causes of inherited PD. This study aimed to screen for LRRK2 variants and assess their effects on PD susceptibility in the Han Chinese population. LRRK2 variants were identified through whole exome sequencing and confirmed by Sanger sequencing in 468 unrelated PD patients and 566 controls. The identified variants were analyzed via bioinformatics predictions and statistical analyses, by interpreting existing literature and database evidence. Twelve variants were detected, including p.A419V, p.P755L, p.I786F, p.C925Y, p.M968K, p.R1067Q, p.R1320S, p.I1339M, p.P1446L, p.D1756Y, p.H2206Y, and p.G2385R. Among participants, 14.74% of PD cases and 7.24% of controls carried at least one LRRK2 variant (odds ratio [OR]: 2.2144, 95% confidence interval [CI]: 1.4728–3.3294, P = 0.0001). The residues p.P755, p.R1067, p.R1320, p.P1446, and p.D1756 are comparatively conserved. The variants p.R1067Q and p.D1756Y, absent in controls, were predicted to be damaging. Compared to controls, PD patients had higher frequencies of p.A419V (OR: 4.2820, 95% CI: 1.4047–13.0530, P = 0.0054, corrected P = 0.0324) and p.G2385R (OR: 2.1149, 95% CI: 1.2682–3.5268, P = 0.0034, corrected P = 0.0324). These findings suggest that the LRRK2 variants, p.R1067Q and p.D1756Y, may act as likely pathogenic variants in PD, while p.A419V and p.G2385R might be risk factors for increased PD susceptibility in the Han Chinese population.
Journal Article
The relationship between social networks and subjective cognitive decline in Chinese younger older adults: the mediating effect of self-perception of aging
2025
Background
Previous studies have emphasized the impact of social networks on cognitive function, but limited attention has been paid to the relationship between social networks and subjective cognitive decline (SCD) and its underlying mechanisms. To provide a theoretical basis for the prevention and management of SCD, this study aimed to investigate the current situation of social networks and SCD among younger older adults, further elucidate the relationship between them, particularly by comparing the impacts of family networks and friend networks on SCD, and explore the role of self-perception of aging (SPA) as a mediator in above associations.
Methods
In this cross-sectional study, we surveyed 652 younger older adults from six cities utilizing a general information questionnaire, the Lubben Social Network Scale-6 (LSNS-6), the Subjective Cognitive Decline Questionnaire (SCD-Q9) and the Brief Ageing Perceptions Questionnaire (B-APQ). Regression models were performed to explore the association between social networks and SCD, while the mediating effect of SPA was examined by using the bootstrap method to validate path effects.
Results
Of the participants, 38.04% of individuals had SCD scores above 50. The prevalence of social isolation was 27.5%, with specific rates of 12.3% for family isolation and 44.9% for friend isolation. After adjusting for key demographic characteristics, it was found that social networks (B = -0.05,
p
< 0.001), especially friend networks (B = -0.07,
p
< 0.01), were negatively associated with SCD. Additionally, SPA was identified as a partial mediator in the relationship between social networks and SCD (B = -0.007, 95% CI: -0.032, -0.002), as well as friend networks and SCD (B = -0.011, 95% CI: -0.021, -0.004).
Conclusions
Younger older adults exhibited a high risk of social isolation, with friend isolation being particularly severe. The significant prevalence of SCD among younger older adults has emerged as a pressing health concern. Social networks exhibited a negative association with SCD, with SPA serving as a mediating role in this relationship. Moving forward, comprehensive interventions aimed at addressing SCD in older adults should consider strategies to enhance social networks and improve SPA.
Journal Article
Ubiquitylation of RUNX3 by RNA-binding ubiquitin ligase MEX3C promotes tumorigenesis in lung adenocarcinoma
by
Sun, Ruifen
,
Zhang, Huijun
,
Xu, Hongbo
in
Adenocarcinoma
,
Adenocarcinoma of Lung - genetics
,
Adenocarcinoma of Lung - pathology
2024
Lung adenocarcinoma (LUAD) is the most common pathological type of lung cancer, but the early diagnosis rate is low. The RNA-binding ubiquitin ligase MEX3C promotes tumorigenesis in several cancers but its mechanism of action in LUAD is unclear. In this study, the biological activity of MEX3C was assessed in LUAD.
MEX3C
and
RUNX3
mRNA levels in the tissues of LUAD patients were determined using reverse transcription‑quantitative PCR. The involvement of MEX3C in the growth and metastasis of LUAD cells was measured by EdU assay, CCK-8, colony formation, Transwell assay, TUNEL, and flow cytometry. Expression of apoptosis and epithelial–mesenchymal transition related proteins were determined using western blotting analysis. LUAD cells transfected with si-MEX3C were administered to mice subcutaneously to monitor tumor progression and metastasis. We found that MEX3C is strongly upregulated in LUAD tissue sections, and involved in proliferation and migration. A549 and H1299 cells had significantly higher levels of MEX3C expression compared to control HBE cells. Knockdown of MEX3C dramatically decreased cell proliferation, migration, and invasion, and accelerated apoptosis. Mechanistically, we demonstrate MEX3C induces ubiquitylation and degradation of tumor suppressor RUNX3. Moreover, RUNX3 transcriptionally represses Suv39H1, as revealed by RNA pull-down and chromatin immunoprecipitation assays. The
in vivo
mice model demonstrated that knockdown of MEX3C reduced LUAD growth and metastasis significantly. Collectively, we reveal a novel MEX3C-RUNX3-Suv39H1 signaling axis driving LUAD pathogenesis. Targeting MEX3C may represent a promising therapeutic strategy against LUAD.
Journal Article
Effect of the Total Saponins of Bupleurum chinense DC. Water Extracts Following Ultrafiltration Pretreatment on Macroporous Resin Adsorption
2024
Macroporous resin is an efficient separation technology that plays a crucial role in the separation and purification of traditional Chinese medicine (TCM). However, the application of macroporous resins in TCM pharmaceuticals is hindered by serious fouling caused by the complex materials used in TCM. This study examines the impact of ultrafiltration (UF) membrane technology on the macroporous resin adsorption behavior of TCM extracts. In this paper, Bupleurum chinense DC. (B. chinense) water extracts were included as an example to study the effect of UF pretreatment on the macroporous resin adsorption of total saponins. The study results indicated that the adsorption of total saponins constituents from the water extracts of B. chinense on the macroporous resin followed the pseudo-second-order kinetic model and the Langmuir model. The thermodynamic parameters of adsorption, including enthalpy changes and Gibbs free energies, were negative, while entropy changes were positive. These results demonstrated that the total saponin components form a monolayer adsorption layer by spontaneous thermal adsorption on the macroporous resin, and that the adsorption rate is not determined by the rate of intraparticle diffusion. Following treatment with a UF membrane with an average molecular weight cut-off of 50 kDa, the protein, starch, pectin, tannin, and other impurities in the water extracts of B. chinense were reduced, while the total saponin content was retained at 82.32%. The adsorption kinetic model of the saponin constituents on the macroporous resin remained unchanged and was consistent with both the second-order kinetic model and the Langmuir model; the adsorption rate of the second-order kinetic model increased by 1.3 times and in the Langmuir model at 25 °C, the adsorption performance improved by 1.16 times compared to the original extracts. This study revealed that UF technology as a pretreatment method can reduce the fouling of macroporous resin by TCM extracts and improve the adsorption performance of macroporous resin.
Journal Article
Correction: DNAH11 compound heterozygous variants cause heterotaxy and congenital heart disease
2024
[This corrects the article DOI: 10.1371/journal.pone.0252786.].
Journal Article