Strategic Lacunes Associated With Mild Cognitive Impairment in Rural Chinese Older Adults: A Population-Based Study.

BACKGROUND: Lacunes are associated with cognitive impairment. We sought to identify strategic lacune locations associated with mild cognitive impairment (MCI) and subtypes of MCI among older adults, and further to examine the role of white matter hyperintensities and perivascular spaces in the association. METHODS: This population-based cross-sectional study included 1230 dementia-free participants in the brain magnetic resonance imaging substudy (2018-2020) in MIND-China (Multimodal Interventions to Delay Dementia and Disability in Rural China). Lacunes were visually identified in frontal lobe, parieto-occipital lobe, temporal lobe, insula, basal ganglia, thalamus, cerebellum, and brainstem. MCI, amnestic MCI (aMCI), and nonamnestic MCI (naMCI) were defined following the Petersen's criteria. Data were analyzed using logistic regression models. RESULTS: Of the 1230 participants (age, ≥60 years; mean age, 69.40; SD, 4.30 years; 58.5% women), lacunes were detected in 357 people and MCI was defined in 286 individuals, including 243 with aMCI and 43 with naMCI. Lacunes in the supratentorial area, internal capsula, putamen/pallidum, and insula was significantly associated with increased odds ratio of MCI (multivariable-adjusted odds ratio ranged 1.40-3.21; P<0.05) and aMCI (multivariable-adjusted odds ratio ranged 1.46-3.36; P<0.05), whereas lacunes in the infratentorial area and brainstem were significantly associated with naMCI (multivariable-adjusted odds ratio ranged 2.68-3.46; P<0.01). Furthermore, the associations of lacunes in insula and internal capsula with MCI and aMCI, as well as the associations of lacunes in infratentorial area and brainstem with naMCI were present independent of white matter hyperintensities volume and perivascular spaces number. CONCLUSIONS: Lacunes in the internal capsula, putamen/pallidum, insula, and brainstem may represent the strategic lacunes that are independently associated with MCI, aMCI, or naMCI in Chinese older adults. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1800017758.

"Light-On" Fluorescent Nanoprobes for Monitoring Dynamic Distribution of Cellular Nucleolin During Pyroptosis.

Nucleolin (NCL) is a multifunctional nuclear protein that plays significant roles in regulating physiological activities of the cells. However, it remains a challenge to monitor the dynamic distribution and expression of nucleolin within living cells during cell stress processes directly. Here, we designed "turn-on" fluorescent nanoprobes composed of specific AS1411 aptamer and nucleus-targeting peptide on gold nanoparticles (AuNPs) to effectively capture and track the NCL distribution and expression during pyroptosis triggered by electrical stimulation (ES). The distribution of nucleolin in the cell membrane and nucleus can be easily observed by simply changing the particle size of the nanoprobes. The present strategy exhibits obvious advantages such as simple operation, low cost, time saving, and suitability for living cell imaging. The ES can induce cancer cell pyroptosis controllably and selectively, with less harm to the viability of normal cells. The palpable cell nuclear stress responses of cancerous cells, including nucleus wrinkling and nucleolus fusion after ES at 1.0 V were obviously observed. Compared with normal cells (MCF-10A), NCL is overexpressed within cancerous cells (MCF-7 cells) using the as-designed nanoprobes, and the ES can effectively inhibit NCL expression within cancerous cells. The developed NCL sensing platform and ES-based methods hold great potential for cellular studies of cancer-related diseases.

Use of peroral cholangiopancreatoscopy-assisted endoscopic mucosal resection for biliopancreatic intraductal lesions.

BACKGROUND AND STUDY AIM: This study aimed to assess the feasibility and safety of performing cholangiopancreatoscopy-assisted endoscopic mucosal resection (CA-EMR) for biliopancreatic intraductal lesions. PATIENTS AND METHODS: Special electrocautery snares and injection needles that can pass through the working channel of a single-operator cholangiopancreatoscope (SOC) were developed. Between November 2023 and April 2024, we performed CA-EMR for 2 patients with gallbladder polyps, 1 patient a neoplastic lesion in the common bile duct (CBD) and 1 patient with a neoplastic lesion in the main pancreatic duct (PD). The technical success rate and adverse events were recorded. RESULTS: All 4 CA-EMR procedures were performed successfully. Postoperative pathology revealed inflammatory gallbladder polyps in 2 patients, low grade intraepithelial neoplasia (LGIN) of CBD in 1 patient and intraductal papillary mucinous neoplasm (IPMN) in 1 patient. The patient with IPMN experienced mild postoperative pancreatitis and recovered after conservative treatment. No adverse events were encountered in the other 3 CA-EMR procedures. CONCLUSION: This study preliminarily confirmed the feasibility and safety of CA-EMR for treating biliopancreatic intraductal lesions.

Unveiling intratumoral microbiota: An emerging force for colorectal cancer diagnosis and therapy.

Microbes, including bacteria, viruses, fungi, and other eukaryotic organisms, are commonly present in multiple organs of the human body and contribute significantly to both physiological and pathological processes. Nowadays, the development of sequencing technology has revealed the presence and composition of the intratumoral microbiota, which includes Fusobacterium, Bifidobacteria, and Bacteroides, and has shed light on the significant involvement in the progression of colorectal cancer (CRC). Here, we summarized the current understanding of the intratumoral microbiota in CRC and outline the potential translational and clinical applications in the diagnosis, prevention, and treatment of CRC. We focused on reviewing the development of microbial therapies targeting the intratumoral microbiota to improve the efficacy and safety of chemotherapy and immunotherapy for CRC and to identify biomarkers for the diagnosis and prognosis of CRC. Finally, we emphasized the obstacles and potential solutions to translating the knowledge of the intratumoral microbiota into clinical practice.

Fibrin sealant for closure of mucosal penetration at the oesophagus or cardia during submucosal tunnelling endoscopic resection for gastrointestinal submucosal tumours.

BACKGROUND AND STUDY AIM: To assess the efficacy and safety of a fibrin sealant for the prevention of leak resulting from mucosal penetration at the esophagus or cardia during a STER procedure to remove gastrointestinal submucosal tumors (SMTs). PATIENTS AND METHODS: Between April 2014 and October 2022, a total of 290 patients with oesophageal or cardiac SMTs underwent STER at our centre. We retrospectively identified patients with oesophageal or cardia SMTs who underwent STER and experienced mucosal penetration of the cardia or oesophagus during the procedure. A total of 31 mucosal penetrations in 30 procedures were included. Of the 31 mucosal penetrations, 12 occurred in the cardia, and the other 19 occurred in the oesophagus. All 31 sites received the fibrin sealant to close the mucosal penetration. Clinical characteristics, procedure-related parameters, detailed data of the mucosal penetrations, and treatment outcomes using the fibrin sealant were reviewed for all 30 patients to assess the efficacy and safety of the fibrin sealant for closure of mucosal penetration at the cardia or oesophagus. RESULTS: For the 31 mucosal penetrations, the mean size was 0.08 ± 0.06 cm2 (range 0.01-0.25 cm2). Mucosal closure using the fibrin sealant was performed successfully in all 31 mucosal penetrations. Of the 31 mucosal penetrations, clips were used in 13 cases. All 30 patients were discharged after a median of 7 days (range 4-20 day) postoperatively. During a mean 62 months (range 6-107 months) follow-up, all 31 mucosal penetrations successfully healed without the occurrence of infection, ulcer, oesophagitis, chest infection or abdominal infection. CONCLUSION: For the closure of mucosal penetration during STER at the cardia or oesophagus, a fibrin sealant is both safe and efficacious. It is necessary to conduct more research on the viability, effectiveness, and safety of using a fibrin sealant to close wider mucosal penetrations.

FAM3D regulation of head and neck squamous cell carcinoma behaviour through the EMT pathway.

OBJECTIVES: Head and neck squamous cell carcinoma present challenges in effective treatment, with 50%-60% of cases exhibiting recurrence or metastasis, often resistant to surgery alone. Immunotherapy, a promising approach, does not guarantee benefits for all patients. Thus, the imperative lies in identifying reliable biomarkers for predicting immunotherapy efficacy. FAM3D, a protein-coding gene known for its potent chemotactic activity in human peripheral blood monocytes and neutrophils, plays a crucial role in regulating tumour immune responses and holds promise as an immune biomarker. MATERIALS AND METHODS: We employed comprehensive database analysis to scrutinise FAM3D, evaluating its gene expression, mutation profiles and prognostic implications in head and neck squamous cell carcinoma, along with its associations with clinical characteristics and immune cell infiltration. Complementary functional experiments were conducted to delve into the potential mechanisms governed by FAM3D. RESULTS: Our findings establish a significant correlation between low FAM3D expression and the invasiveness and metastatic potential of head and neck squamous cell carcinoma. FAM3D likely exerts its influence through the regulation of epithelial-mesenchymal transition. CONCLUSIONS: FAM3D emerges as a valuable biomarker for predicting the responsiveness of patients with head and neck squamous cell carcinoma to immunotherapy, holding substantial clinical diagnostic and therapeutic relevance.

First Report of Bacterial Leaf Streak of Rice Caused by Pantoea ananatis in Guangdong Province, China.

Rice (Oryza sativa L.) is a crucial staple crop worldwide, and bacterial diseases are among the primary factors affecting rice yield. In late October 2022, bacterial leaf streak disease was observed on the leaves of the rice variety Meixiangzhan 2 across multiple fields (approximately 130 hm2) in Leizhou City, Guangdong Province, China. The incidence rate was up to 30% in each field. Infected rice leaves exhibited distinctive symptoms at the boundary between diseased and healthy tissue, featuring dark green to yellow-brown streaks, while most of the leaf margin exhibited symptoms of either leaf edge or sheath rot. Disease progression from the leaf tip inwards revealed gray-white or dehydrated lesions with a bluish-gray color. Some leaves exhibited wrinkling at the edges, and severe symptoms at the leaf tip resembled those of bacterial leaf blight in rice. Ten leaves were collected from 10 infected rice plants in three distinct fields, and leaf pieces at the border of diseased and healthy areas were surface disinfected with 75% anhydrous ethanol for 60 seconds, rinsed three times with sterile water, and then soaked in sterile water for 8 hours. The obtained bacterial suspension was diluted at a ratio of 1: 106, and 100 µL of the diluted samples were plated on Potato Dextrose Agar (PDA) plates. After incubation at 28°C for 48 hours, the yellow bacterial colonies that appeared, were purified on PDA plates. To confirm the bacterial species, the amplification of genes gyrB, leuS, rpoB, and 16S rDNA was performed on six randomly selected isolates from the three different fields using the primers 27F/1492R, gyrB-F/R, leuS-F/R and rpoB-F/R, as reported by Yu et al (2022), respectively. PCR products were sequenced. All six isolates had identical sequences for all genes sequenced.The gene sequences of 16S rDNA (960 bp), gyrB (953 bp), leuS (733 bp), and rpoB (877 bp) for LZ1, were deposited in the NCBI database under accession numbers PP048830 , PP068625 , PP068626, and PP068627, respectively. These sequences were subsequently compared using BLASTn tool against the NCBI nr/nt database. The 16S rDNA, gyrB, leuS, and rpoB of LZ1 showed similarities of 99.90%, 99.16%, 99.73%, and 99.89%, with the corresponding sequences of P. ananatis TZ39 (GenBank accession numbers MZ800600.1 for 16S rDNA, and CP081342.1 for gyrB, leuS and rpoB ). MLSA analysis using concatenated sequences of gyrB, leuS, and rpoB genes indicated that the isolated strain LZ1 belongs to P. ananatis. In the tillering stage of rice varieties Meixiangzhan 2 and Huahangyuzhan, P. ananatis LZ1 was inoculated at a concentration of 108 CFU/mL using the leaf-cutting method, with sterile water used as a control (Toh et al., 2019). After 14 days of bacterial inoculation, the inoculated leaves gradually became necrotic, changing from light green to brown showing identical symptoms as those in the field, while the control plants remained symptom-free. Subsequent 16S rDNA, gyrB, leuS and rpoB gene sequencing results further confirmed the identity of the pathogen as P. ananatis, thereby fulfilling Koch's postulates. Previous reports have already identified P. ananatis as the pathogen causing rice bacterial leaf streak (Kini et al., 2017; Arayaskul et al., 2019; Yu et al., 2022; Lu et al., 2022; Luna et al., 2023; Yuan et al., 2023). This is the first report of rice bacterial leaf streak caused by P. ananatis in Guangdong Province, China, laying the foundation for future research to establish strategies for the prevention and control of this disease.

Unveiling the Role of RNA Recognition Motif Proteins in Orchestrating Nucleotide-Binding Site and Leucine-Rich Repeat Protein Gene Pairs and Chloroplast Immunity Pathways: Insights into Plant Defense Mechanisms.

In plants, nucleotide-binding site and leucine-rich repeat proteins (NLRs) play pivotal roles in effector-triggered immunity (ETI). However, the precise mechanisms underlying NLR-mediated disease resistance remain elusive. Previous studies have demonstrated that the NLR gene pair Pik-H4 confers resistance to rice blast disease by interacting with the transcription factor OsBIHD1, consequently leading to the upregulation of hormone pathways. In the present study, we identified an RNA recognition motif (RRM) protein, OsRRM2, which interacted with Pik1-H4 and Pik2-H4 in vesicles and chloroplasts. OsRRM2 exhibited a modest influence on Pik-H4-mediated rice blast resistance by upregulating resistance genes and genes associated with chloroplast immunity. Moreover, the RNA-binding sequence of OsRRM2 was elucidated using systematic evolution of ligands by exponential enrichment. Transcriptome analysis further indicated that OsRRM2 promoted RNA editing of the chloroplastic gene ndhB. Collectively, our findings uncovered a chloroplastic RRM protein that facilitated the translocation of the NLR gene pair and modulated chloroplast immunity, thereby bridging the gap between ETI and chloroplast immunity.

Lateral lymph node metastasis in papillary thyroid cancer: Is there a difference between PTC and PTMC?

Papillary thyroid carcinoma (PTC) and papillary thyroid microcarcinoma (PTMC) are generally characterized as less invasive forms of thyroid cancer with favorable prognosis. However, once lateral cervical lymph node metastasis takes place, the prognosis may be significantly impacted. The purpose of this study was to evaluate whether there is a difference in the pattern of lateral lymph node metastasis between PTC and PTMC. A retrospective analysis was performed for PTC and PTMC patients that underwent central area dissection and unilateral lateral neck lymph node dissection (II-V area) between January 2020 and December 2021. Compared with PTMC group, the PTC group exhibited higher incidence of capsule invasion, extrathyroid invasion and lymphatic vessel invasion. Both the number and rate of central lymph nodes metastasis were elevated in the PTC group. While the number of lateral cervical lymph node metastasis was higher, the metastasis rate did not demonstrate significant difference. No significant differences were identified in the lymph node metastasis patterns between the 2 groups. The determination of the extent of lateral neck lymph node dissection solely based on the tumor size may be unreliable, as PTC and PTMC showed no difference in the number and pattern of lateral neck metastasis. Additional clinical data are warranted to reinforce this conclusion. For patients categorized as unilateral, bilateral, or contralateral cervical lymph node metastasis (including level I, II, III, IV, or V) or retropharyngeal lymph node metastasis who require unilateral lateral neck dissection, the size of the primary tumor may not need to be a central consideration when assessing and deciding the extent of lateral neck dissection.

Variance, norms and cooperative behavior in public goods games.

This study examines the relationship between the variance of others' contributions, social norms (empirical and normative expectations), and cooperative behavior using a classic linear public goods game. The following results are observed. First, the variance of a participant's group members' contributions had a negative impact on their contributions, empirical expectations, and normative expectations. Second, deviations from the mean, whether negative or positive, were deemed less socially appropriate. Third, while there was a strong relationship between variance, social norms, and cooperative behavior, the mediating effect of social norms was found to be insignificant. Finally, there were some notable findings regarding behavior type. Although free riders and cooperators exhibited distinct behavioral patterns, their normative expectations were similar. Free riders expected others to cooperate, but their empirical expectations were significantly lower than cooperators' expectations, which were aligned with their actual contributions. These findings contribute to research on the relationship between distribution heterogeneity, social norms and cooperative behavior. Furthermore, these findings provide valuable insights into management practices.

HPLC with chiral stationary phase for separation and kinetics study of aspartic acid epimerization in Peroxiredoxin 2 active site peptide.

Amino acid epimerization, a process of converting L-amino acids to D-amino acids, will lead to modification in the protein structure and, subsequently, its biological function. This modification causes no change in protein m/z and may be overlooked during protein analysis. Aspartic Acid Epimerization (AAE) is faster than other amino acids and could be accelerated by free radicals and peroxides. In this work, a novel and site-specific HPLC method using a chiral stationary phase for determining the AAE in the active site model peptide (AP) of Peroxiredoxin 2 has been developed and validated. The developed method showed good linearity (1 - 200 µg/mL) and recoveries of the limit of quantification (LOQ), low, medium, and high concentrations were between 85% and 115%. The Kinetics of AAE in AP were studied using the developed method, and the results showed that when ascorbic acid and Cu2+ coexisted, the AP epimerized rapidly. The AAE extent increased with time and was positively correlated with hydrogen peroxide generation.

Can NPC1L1 inhibitors reduce the risk of biliary tract cancer? Evidence from a mendelian randomization study.

BACKGROUND & AIMS: Oxysterols have been implicated in biliary tract cancer (BTC), and Niemann-Pick C1-like 1 (NPC1L1) has been associated with oxysterol uptake in biliary and intestinal cells. Thus, our study aims to investigate the potential causal link between genetically proxied NPC1L1 inhibitors and the risk of BTC. METHODS: In this study, we employed two genetic instruments as proxies for NPC1L1 inhibitors, which included LDL cholesterol-associated genetic variants located within or in close proximity to the NPC1L1 gene, as well as expression quantitative trait loci (eQTLs) of the NPC1L1 gene. Effect estimates were calculated using the Inverse-variance-weighted MR (IVW-MR) and summary-data-based MR (SMR) methods. RESULTS: In MR analysis using the IVW method, both proxy instruments from the UK Biobank and the GLGC demonstrated a positive association between NPC1L1-mediated LDL cholesterol and BTC risk, with odds ratios (OR) of 10.30 (95% CI = 1.51-70.09; P = 0.017) and 5.61 (95% CI = 1.43-21.91; P = 0.013), respectively. Moreover, SMR analysis revealed a significant association between elevated NPC1L1 expression and increased BTC risk (OR = 1.19, 95% CI = 1.04-1.37; P = 0.014). CONCLUSIONS: This MR study suggests a causal link between NPC1L1 inhibition and reduced BTC risk. NPC1L1 inhibitors, like ezetimibe, show potential for chemoprevention in precancerous BTC patients, requiring further clinical investigation.

Coaxial Electrospun Polycaprolactone/Gelatin Nanofiber Membrane Loaded with Salidroside and Cryptotanshinone Synergistically Promotes Vascularization and Osteogenesis.

Background: Salidroside (SAL) is the most effective component of Rhodiola rosea, a traditional Chinese medicine. Cryptotanshinone (CT) is the main fat-soluble extract of Salvia miltiorrhiza, exhibiting considerable potential for application in osteogenesis. Herein, a polycaprolactone/gelatin nanofiber membrane loaded with CT and SAL (PSGC membrane) was successfully fabricated via coaxial electrospinning and characterized. Methods and Results: This membrane capable of sustained and controlled drug release was employed in this study. Co-culturing the membrane with bone marrow mesenchymal stem cells and human umbilical vein endothelial cells revealed excellent biocompatibility and demonstrated osteogenic and angiogenic capabilities. Furthermore, drug release from the PSGC membrane activated the Wnt/ß-catenin signaling pathway and promoted osteogenic differentiation and vascularization. Evaluation of the membrane's vascularization and osteogenic capacities involved transplantation onto a rat's subcutaneous area and assessing rat cranium defects for bone regeneration, respectively. Microcomputed tomography, histological tests, immunohistochemistry, and immunofluorescence staining confirmed the membrane's outstanding angiogenic capacity two weeks post-operation, with a higher incidence of osteogenesis observed in rat cranial defects eight weeks post-surgery. Conclusion: Overall, the SAL- and CT-loaded coaxial electrospun nanofiber membrane synergistically enhances bone repair and regeneration.

Dual-signal readout sensing of ATP content in single dental pulp stem cells during differentiation via functionalized glass nanopipettes.

Adenosine triphosphate (ATP) is regarded as the "energy currency" in living cells, so real-time quantification of content variation of intracellular ATP is highly desired for understanding some important physiological processes. Due to its single-molecule readout ability, nanopipette sensing has emerged as a powerful technique for molecular sensing. In this study, based on the effect of targeting-aptamer binding on ionic current, and fluorescence resonance energy transfer (FRET), we reported a dual-signal readout nanopipette sensing system for monitoring ATP content variation at the subcellular level. In the presence of ATP, the complementary DNA-modified gold nanoparticles (cDNAs-AuNPs) were released from the inner wall of the nanopipette, which leads to sensitive response variations in ionic current rectification and fluorescence intensity. The developed nanopipette sensor was capable of detecting ATP in single cells, and the fluctuation of ATP content in the differentiation of dental pulp stem cells (DPSCs) was further quantified with this method. The study provides a more reliable nanopipette sensing platform due to the introduction of fluorescence readout signals. Significantly, the study of energy fluctuation during cell differentiation from the perspective of energy metabolism is helpful for differentiation regulation and cell therapy.

Sophora flavescens-Angelica sinensis in the treatment of eczema by inhibiting TLR4/MyD88/NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Sophora flavescens Ait.-Angelica sinensis(Oliv.) Diels drug pairing (SA) is a transformed drug pairing from Shengui pill, a traditional Chinese medicine prescription in the ninth volume of Traditional Chinese Medicine classic "Gu Jin Yi Jian", which is famous for clearing heat, moistening dryness, and promoting blood circulation. It is commonly used in the treatment of eczema, a skin condition that causes itching and inflammation. Despite its widespread use, there is still limited research on the mechanism of how SA treats eczema. This paper aims to fill this gap by conducting animal experiments to uncover the mechanism behind SA's therapeutic effects on eczema. Our findings provide a solid foundation for the clinical use of this TCM prescription. AIM OF THE STUDY: The basic purpose of this study is to clarify the therapeutic mechanism of Sophora flavescens-Angelica sinensis (SA) in the treatment and control of eczema. MATERIALS AND METHODS: The chemical compositions of SA were analyzed using HPLC-Q-Orbitrap-MS. In vivo, a mouse model of eczema was created, and the serum levels of TNF-α and IL-1ß were quantified using an enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (HE) staining was performed to assess the pathological state of the mouse skin, and immunohistochemical technique (IHC) was employed to estimate the contents of TNF-α, TLR4, and NF-κB semi-quantitatively. The expression levels of TLR4, MyD88, and NF-κB mRNA were determined through real-time quantitative polymerase chain reaction (qRT-PCR). Western Blotting was utilized to identify the protein levels of TLR4, MyD88, and NF-κB in mouse skin tissue. RESULTS: SA identified 18 active chemicals, some of which were shown in vivo to inhibit the TLR4/MyD88/NF-κB signaling pathway while reducing serum levels of TNF-α and IL-1ß, making them ideal agents for the treatment of eczema. CONCLUSIONS: SA's anti-inflammatory properties are attributed to its ability to reduce serum levels of TNF-α and IL-1ß, likewise inhibit the TLR4/MyD88/NF-κB signaling pathway.

Regulation of the immune microenvironment by pioglitazone-loaded polylactic glycolic acid nanosphere composite scaffolds to promote vascularization and bone regeneration.

Osteogenesis is caused by multiple factors, and the inflammatory response, osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), regeneration of blood vessels, and other factors must be considered in bone tissue engineering. To effectively repair bone defect, it is important to decrease excessive inflammation, enhance the differentiation of mesenchymal stem cells into osteoblasts, and stimulate angiogenesis. Herein, nano-attapulgite (ATP), polyvinyl alcohol (PVA), and gelatin (GEL) scaffolds were produced using 3D printing technology and pioglitazone (PIO)-containing polylactic acid-glycolic acid (PLGA) nanospheres were added. In both in vitro and in vivo studies, material scaffolds with PIO-loaded polylactic acid-glycolic acid nanospheres could reduce the inflammatory response by encouraging macrophage polarization from M1 to M2 and promoting the osteogenic differentiation of BMSCs by activating the BMP2/Smad/RUNX2 signal pathway to repair bone defects. The vascularization of human umbilical vein endothelial cells (HUVECs) through the PI3K/AKT/HIF1-/VEGF pathway was also encouraged. In vivo research using PIO-containing PLGA nanospheres revealed massive collagen deposition in skin models. These findings indicate a potentially effective scaffold for bone healing, when PLGA nanospheres-which contain the drug PIO-are combined with ATP/PVA/GEL scaffolds.

Association of late-life blood pressure change with cerebral small vessel disease in the MIND-China study.

OBJECTIVES: This study aimed to investigate the associations between changes in blood pressure (BP) and cerebral small vessel disease (CSVD). METHODS: This study included 401 participants in the magnetic resonance imaging (MRI) sub-study conducted between 2018 and 2020 as a part of the Multidomain Interventions to Delay Dementia and Disability in Rural China project. MRI markers of CSVD were assessed based on international criteria. Individualized linear regression models evaluated changes in BP by estimating the trend of blood pressure changes over time and fitting a straight line from 2014 to 2018. The data were analyzed using logistic and general linear regression models. RESULT: The mean age of the participants was 64.48 ± 2.69 years, with 237 (59.1%) being females. Increases in systolic BP in later life were significantly associated with larger volumes of periventricular white matter hyperintensity (WMH), greater perivascular spaces in the basal ganglia (BG-PVS) burden, and the presence of deep lacunes and cerebral microbleeds. Additionally, increases in diastolic BP in later life were significantly associated with the presence of infratentorial and deep lacunes. CONCLUSIONS: CSVDs are associated with increased exposure to elevated BP later in life.