Strategically designed metal-free deep-ultraviolet birefringent crystals with superior optical properties.

Finding new birefringent materials with deep-ultraviolet (DUV, λ < 200 nm) transparency is urgent, as current commercial materials cannot meet the rapidly growing demands in related application fields. Herein, three guanidinium-based compounds, C(NH2)3CH3SO3, ß-C(NH2)3Cl, and γ-C(NH2)3Cl, all featuring [C(NH2)3·X]∞ (X = CH3SO3 and Cl) pseudo layers, were designed through structural motif tailoring. Theoretical calculations indicate that these metal-free compounds all possess broad bandgaps (6.49-6.71 eV, HSE06) and remarkable birefringence (cal. 0.166-0.211 @ 1064 nm). Centimeter-sized C(NH2)3CH3SO3 crystals have been grown using a feasible aqua-solution method. Subsequently, to further optimize the properties, ß/γ-C(NH2)3Cl was remolded by further tailoring the [C(NH2)3]+ cationic unit and the acceptor Cl- anion, and then the fourth compound NH2COF was theoretically constructed. Interestingly, NH2COF exhibits the desired coexistence of a wider bandgap (7.87 eV, HSE06) and giant birefringence (cal. 0.241 @ 1064 nm) attributed to its higher density of well-aligned birefringence-active groups (BAGs). Furthermore, among these four designed compounds, C(NH2)3CH3SO3 has been experimentally synthesized and exhibits a short UV cutoff edge. Centimeter-sized crystals have been grown using a feasible aqueous solution method. This study provides an effective strategy to optimize the density of BAGs for large birefringence and offers valuable insights into the strategic design of metal-free DUV birefringent crystals.

Development of measured hydrodynamic information-based flood early warning system for small streams.

In general, small stream basins, characterized by narrow channels and steep slopes, face heightened vulnerability to climate change-induced flooding, posing challenges for evacuation procedures. With the increasing intensity of floods and typhoons in recent years, urgent measures are necessary to mitigate damage in such areas. This research endeavors to address these challenges by developing a novel small stream flood early warning system (SSFEWS) tailored to small streams and piloting its application. The proposed system integrates real-time hydrodynamic data collection, flood probability forecasting, and proactive warning issuance through an amalgamation of IoT-based sensor networks, statistical models leveraging measurement data, a robust constrained nonlinear optimization algorithm (RCNOA), and four-parameter logistic method (4PL). Moreover, system accuracy and reliability are enhanced by an automated iterative process that continuously refines forecasting model parameters via a user-defined rainfall-discharge nomograph and rating curve using RCNOA and 4PL. The developed SSFEWS is expected to contribute to the safety of the community as well as prevent possible small stream-related casualties by enabling efficient disaster response. © 2024 Elsevier Ltd. All rights reserved.

Platycodon grandiflorum exhibits anti-neuroinflammatory potential against beta-amyloid-induced toxicity in microglia cells.

Background/objectives: Platycodon grandiflorum (PG) is used in traditional oriental medicine to treat several ailments. Methods: The study investigated the anti-inflammatory and neuroprotective effects of PGW (P. grandiflorum) extract in Aß25-35-induced inflammation in BV2 microglia cells. Result: PGW demonstrated significant inhibition of nitric oxide (NO) production, with reductions of 30.4, 36.7, and 61.2% at concentrations of 50, 100, and 200 µg/mL, respectively. Moreover, PGW effectively suppressed the production of pro-inflammatory cytokines IL-1ß and IL-6 and exhibited significant inhibitory activity against TNF-α at 200 µg/mL. Furthermore, PGW treatment mitigated apoptosis in Aß-induced BV2 cells by modulating the mitochondrial apoptosis pathway, regulating Bcl-2 family protein synthesis, and inhibiting caspase activation. Mechanistically, PGW attenuated the activation of the MAPK (JNK, ERK, p38) pathway induced by Aß, showing a concentration-dependent decrease in phosphorylation levels of these proteins. Additionally, PGW inhibited the NF-κB pathway activation by reducing the phosphorylation levels of p65 and IκBα in a concentration-dependent manner. Conclusion: PGW demonstrated anti-inflammatory and neuroprotective effects in Aß-induced neuronal cells, suggesting its potential as a therapeutic agent for neuroinflammatory associated with neurodegenerative diseases.

Effect of acacetin on inhibition of apoptosis in Helicobacter pylori-infected gastric epithelial cell line.

BACKGROUND: Helicobacter pylori (H. pylori) infection can cause extensive apoptosis of gastric epithelial cells, serving as a critical catalyst in the progression from chronic gastritis, gastrointestinal metaplasia, and atypical gastric hyperplasia to gastric carcinoma. Prompt eradication of H. pylori is paramount for ameliorating the pathophysiological conditions associated with chronic inflammation of the gastric mucosa and the primary prevention of gastric cancer. Acacetin, which has multifaceted pharmacological activities such as anti-cancer, anti-inflammatory, and antioxidative properties, has been extensively investigated across various domains. Nevertheless, the impact and underlying mechanisms of action of acacetin on H. pylori-infected gastric mucosal epithelial cells remain unclear. AIM: To explore the defensive effects of acacetin on apoptosis in H. pylori-infected GES-1 cells and to investigate the underlying mechanisms. METHODS: GES-1 cells were treated with H. pylori and acacetin in vitro. Cell viability was assessed using the CCK-8 assay, cell mortality rate via lactate dehydrogenase assay, alterations in cell migration and healing capacities through the wound healing assay, rates of apoptosis via flow cytometry and TUNEL staining, and expression levels of apoptosis-associated proteins through western blot analysis. RESULTS: H. pylori infection led to decreased GES-1 cell viability, increased cell mortality, suppressed cell migration, increased rate of apoptosis, increased expressions of Bax and cle-caspase3, and decreased Bcl-2 expression. Conversely, acacetin treatment enhanced cell viability, mitigated apoptosis induced by H. pylori infection, and modulated the expression of apoptosis-regulatory proteins by upregulating Bcl-2 and downregulating Bax and cleaved caspase-3. CONCLUSION: Acacetin significantly improved GES-1 cell viability and inhibited apoptosis in H. pylori-infected GES-1 cells, thereby exerting a protective effect on gastric mucosal epithelial cells.

Different characteristics between acute and delayed proximal junctional failure in elderly patients undergoing corrective surgery for adult spinal deformity: Comparative analysis of risk factor, failure mode, and clinical consequences.

BACKGROUND CONTEXT: While numerous studies have been conducted on proximal junctional failure (PJF), the clinical significance of acute and delayed PJF remains poorly understood. PURPOSE: The primary object of this study is to investigate the risk factors separately for acute and delayed PJF. Secondly, we aim to assess the incidence of each failure mode and their clinical consequences in relation to acute and delayed PJF. STUDY DESIGN/SETTING: Retrospective comparative study. PATIENT SAMPLE: Patients aged ≥60 years who underwent deformity correction with ≥5-level fusion to sacrum. OUTCOME MEASURES: Risk factor, failure modes, and patient-reported outcome measure (PROM) METHODS: Acute PJF is defined as PJF occurring within 6 months, while delayed PJF occurring after 6 months. Risk factors were analyzed by comparing various clinical and radiographic parameters among three groups: no, acute, and delayed PJF groups. The failure modes, including soft tissue failure, vertebral fracture, fixation failure, and myelopathy, were compared among these groups. The clinical subsequences after PJF development were evaluated by assessing the change in proximal junctional angle (PJA), revision rate, and patient-reported outcome measure (PROM). RESULTS: A study cohort of 363 patients was included in the analysis. Among them, 156 patients experienced PJF, with 87 patients (55.8%) in the acute PJF group and 69 patients (44.2%) in the delayed PJF group. Multivariate analyses showed that older age (Odds ratio [OR] = 1.057, 95% confidence interval [CI] = 1.002 - 1.118), osteoporosis (OR=2.149, 95% CI = 1.074 - 4.300), high American Society of Anesthesiology ASA score (OR=2.150, 95% CI = 1.089 - 4.245), and overcorrection relative to the age-adjusted pelvic incidence - lumbar lordosis target (OR=4.031, 95% CI = 1.962 - 8.280) were identified as risk factors for the development of acute PJF. On the other hand, a high body mass index (OR=1.150, 95% CI = 1.049 - 1.251) and an uppermost instrumented vertebra located at ≤ T10 (OR=2.267, 95% CI = 1.205 - 4.268) were found to be associated with delayed occurrence of PJF. No radiographic parameters were found to be related to the development of delayed PJF. In terms of failure modes, vertebral fracture and fixation failure were more commonly observed in acute PJF, while soft tissue failure and myelopathy were more predominant in delayed PJF. The clinical course was more aggressive in the acute PJF group compared to the delayed PJF group, as evidenced by a greater increase in PJA, a higher revision rate, and worse PROM. CONCLUSIONS: This study demonstrated different risk factors between the acute and delayed PJF. It was found that overcorrection relative to the age-adjusted PI-LL target increased the risk of acute PJF, but had no impact on the development of delayed PJF. Therefore, a different surgical strategy needs to be established to mitigate both acute and delayed PJF.

Higher serum uric acid as a risk factor for frailty in older adults: A nationwide population-based study.

BACKGROUND: Uric acid (UA), the terminal breakdown product of purine metabolism, possesses contradictory roles, functioning both as an inflammatory mediator and as an antioxidant. Its clinical relevance, particularly in geriatric populations, remains a topic of ongoing debate. Aiming to elucidate whether circulating UA is detrimental or beneficial to human health, we investigate the association between serum UA concentrations and the frailty index-a comprehensive measure of biological aging in a nationally representative cohort of community-dwelling older adults. METHODS: We conducted a population-based, cross-sectional study utilizing data from the Korea National Health and Nutrition Examination Survey. The sample included 4268 participants aged 65 years and above. A deficit accumulation frailty index (FI) was constructed using 38 items that assess physical, cognitive, psychological, and social domains. Based on the FI, participants were categorized into non-frail (FI ≤ 0.15), pre-frail (0.15 < FI ≤ 0.25), or frail (FI > 0.25). Serum UA levels were quantified through a colorimetric enzymatic assay. RESULTS: After controlling for confounders such as age, sex, socioeconomic status (including income and education level), lifestyle factors (smoking status), and medical history (hypertension, diabetes, dyslipidemia, stroke, cardiovascular diseases), and body mass index, serum UA levels were observed to be significantly higher in frail participants compared with their non-frail counterparts (P < 0.001). Furthermore, serum UA concentrations demonstrated a positive correlation with the FI (P < 0.001), and the odds ratio for frailty per 1 mg/dL increase in serum UA was 1.22 (P < 0.001). Additionally, older adults in the highest quartile of UA levels exhibited a significantly higher FI and 1.66-fold increased odds of frailty compared with those in the lowest quartile (P = 0.011 and P = 0.005, respectively). CONCLUSIONS: These findings suggest that elevated circulating UA levels may act as a pro-aging factor rather than an anti-aging one in older adults, highlighting its potential role in accelerating biological aging. The data further support the utility of serum UA as a potential blood-based biomarker for frailty in this demographic, contributing to the expanding evidence on its significance in geriatric health assessments.

Polymer Hosts Containing Carbazole-Dibenzothiophene-Based Pendants for Application in High-Performance Solution-Processed TADF-OLEDs.

The film-forming capability of the host plays a crucial role in effectively forming a light-emitting layer through a solution process in organic light-emitting diodes (OLEDs). In this study, we synthesized two side-chain polymer hosts, PCz-DBT and P2Cz-DBT, consisting of carbazole and dibenzothiophene. The synthesis was carried out through radical polymerization using styrene-based host monomers. Their photophysical characteristics and molecular energy levels are similar to those of the reference small molecule hosts, namely, Cz-DBT and 2Cz-DBT. However, compared to the small-molecule hosts Cz-DBT and 2Cz-DBT, the two polymer hosts showed high thermal stability and good film-forming properties in the neat and host-emitter blend films. Specifically, bluish-green multiple-resonance (MR) thermally activated delayed fluorescence (TADF) OLEDs, fabricated via solution processing with an emissive layer based on P2Cz-DBT, exhibited remarkable performance. These devices achieved a maximum external quantum efficiency of 17.4% without utilizing a hole transport layer. This polymer host design strategy is considered to significantly contribute to enhancing the performance of TADF-OLEDs fabricated through solution processing.

Ursodeoxycholic acid is associated with better clinical outcomes in COVID-19 patients: A population-based cohort study.

BACKGROUND: Several studies have investigated the relationship between ursodeoxycholic acid (UDCA) and coronavirus disease 2019 (COVID-19). However, complex and conflicting results have generated confusion in the application of these results. OBJECTIVE: We aimed to investigate whether the association between UDCA and COVID can also be demonstrated through the analysis of a large-scale cohort. METHODS: This retrospective study used local and nationwide cohorts, namely the Jeonbuk common data model cohort (JBUH CDM) and the Korean National Health Insurance claim-based database (NHIS). We investigated UDCA intake and its relationship with COVID-19 susceptibility and severity using validated propensity score (PS) matching. RESULTS: Regarding the COVID-19 susceptibility, the adjusted hazard ratio (aHR) value of the UDCA intake was significantly lowered to 0.71 in the case of JBUH CDM (95% confidence interval (CI): 0.52-0.98), and was significantly lowered to 0.93 (95% CI: 0.90-0.96) in the NHIS. Regarding the COVID-19 severity, the UDCA intake was found to be significantly lowered to 0.21 (95% CI: 0.09-0.46) in the case of JBUH CDM. It was also found that the aHR value was significantly lowered to 0.77 in the case of the NHIS (95% CI: 0.62-0.95). CONCLUSIONS: Using a large-scale local and nationwide cohort, we confirmed that UDCA intake was significantly associated with the reduction of COVID-19 susceptibility and severity. These trends remained consistent regardless of the UDCA dosage. This suggests the potential of UDCA as a preventive and therapeutic agent for COVID-19.

Analysis of prefrontal cerebral blood volume and flow changes in ESKD patients undergoing hemodialysis using functional near-infrared spectroscopy.

BACKGROUND: End-stage kidney disease (ESKD) patients undergoing hemodialysis experience diverse neurological complications. This study investigated prefrontal cerebral blood volume (CBV) and cerebral blood flow (CBF) during hemodialysis using functional near-infrared spectroscopy (fNIRS) to analyze cerebral hemodynamic changes. METHODS: ESKD patients undergoing maintenance hemodialysis without a history of neurological disorders were enrolled prospectively. The fNIRS data were collected using a NIRSIT Lite device. The fNIRS values were recorded three times for each patient: before the start of hemodialysis (pre-HD), 1 h after the start of hemodialysis (mid-HD), and after the end of hemodialysis (post-HD). The average changes in oxy-hemoglobin (HbO2), deoxy-hemoglobin (HbR), total hemoglobin (HbT, calculated as HbO2 + HbR) concentrations, and in hemoglobin concentration difference (HbD, calculated as HbO2 - HbR) were analyzed. We then compared the differences in changes in HbO2, HbR, HbT, and HbD according to the hemodialysis period. RESULTS: Thirty hemodialysis patients were analyzed. The change in HbO2, HbT, and HbD levels showed significant differences according to the hemodialysis period. Between the pre-HD and post-HD periods, there were significant differences in changes in HbO2 (0.005 ± 0.001 µM vs. 0.015 ± 0.004 µM, p = .046) and HbT (0.006 ± 0.001 µM vs. 0.016 ± 0.008 µM, p = .029). Additionally, between pre-HD and post-HD periods, HbD tended to increase (0.005 ± 0.001 µM vs. 0.014 ± 0.004 µM, p = .094). CONCLUSIONS: We demonstrated that during one hemodialysis session, the relative change in prefrontal CBV increased post-HD compared with pre-HD. These results are expected to help understanding the mechanisms underlying the effects of hemodialysis on brain function.

Metabolomic analysis combined with machine learning algorithms enables the evaluation of postharvest pecan color stability.

Nut kernel color is a crucial quality indicator affecting the consumers first impression of the product. While growing evidence suggests that plant phenolics and their derivatives are linked to nut kernel color, the compounds (biomarkers) responsible for kernel color stability during storage remain elusive. Here, pathway-based metabolomics with machine learning algorithms were employed to identify key metabolites of postharvest pecan color stability. Metabolites in phenylpropanoid, flavonoid, and anthocyanin biosynthetic pathways were analyzed in the testa of nine pecan cultivars using liquid chromatography-mass spectrometry. With color measurements, different machine learning models were compared to find relevant biomarkers of pecan color phenotypes. Results revealed potential marker compounds that included flavonoid precursors and anthocyanidins as well as anthocyanins (e.g., peonidin, delphinidin-3-O-glucoside). Our findings provide a foundation for future research in the area, and will help select genes/proteins for the breeding of pecans with stable and desirable kernel color.

Alterations in functional brain connectivity following treatment for restless legs syndrome: The role of symptom improvement in restoring functional connectivity.

The pathophysiology of restless legs syndrome (RLS) remains incompletely understood. Although several studies have investigated the alterations of brain connectivity as one of the pathophysiological mechanisms of RLS, there are only few reports on functional connectivity changes after RLS treatment. Forty-nine patients with newly diagnosed RLS and 50 healthy controls were prospectively enrolled. The patients underwent resting-state functional magnetic resonance imaging (rs-fMRI) at baseline, and 39 patients underwent follow-up rs-fMRI, 3 months after treatment with pramipexole or pregabalin. Patients were divided into good or poor medication response groups. Functional brain connectivity was analysed using rs-fMRI and graph theoretical analysis. Significant differences in functional connectivity were observed between the RLS patients and healthy controls. The average path length, clustering coefficient, transitivity, and local efficiency were lower (2.02 vs. 2.30, p < 0.001; 0.45 vs. 0.56, p < 0.001; 3.08 vs. 4.21, p < 0.001; and 0.71 vs. 0.76, p < 0.001, respectively) and the global efficiency was higher (0.53 vs. 0.50, p < 0.001) in patients with RLS than in healthy controls. Differences in functional connectivity at the global level were also observed between post- and pre-treatment RLS patients who showed a good medication response. Transitivity in the post-treatment group was higher than that in the pre-treatment group (3.22 vs. 3.04, p = 0.007). Global efficiency was positively correlated with RLS severity (r = 0.377, p = 0.007). This study demonstrates that RLS is associated with distinct alterations in brain connectivity, which can be partially normalised following symptom management. These findings suggest that therapeutic interventions for RLS modulate brain function, emphasising the importance of symptom-focussed treatment in managing RLS.

Effect of intramolecular energy transfer in a dual-functional molecular dyad on the performance of solution-processed TADF OLEDs.

This paper introduces the design concept of a dual-functional molecular dyad tailored specifically for solution-processable organic light-emitting diodes (OLEDs). Cy-tmCPBN, characterized by an asymmetric molecular dyad structure, integrates a host unit (tmCP) and a multiple-resonance (MR) emitter (CzBN) via a non-conjugated cyclohexane linker. Cy-tmCPBN exhibited efficient intramolecular energy transfers (EnTs) from tmCP to the CzBN unit, as confirmed by time-resolved fluorescence experiments. The fluorescence lifetime of the tmCP unit was approximately three times shorter in a highly diluted solution of Cy-tmCPBN than in a mixed solution of Cy-tmCP and Cy-CzBN. In addition, Cy-tmCPBN exhibited excellent solubility and film-forming ability, making it suitable for solution processing. Notably, OLEDs utilizing Cy-tmCPBN achieved over twice the brightness and improved external quantum efficiency of 12.3% compared to OLEDs using Cy-CzBN with the same concentration of CzBN in the emitting layer. The improved OLED performance can be explained by the increased EnT efficiency from Cy-tmCP to Cy-tmCPBN and the intramolecular EnT within Cy-tmCPBN. In our dual-functional dyad, incorporating both host and emitter units in an asymmetric molecular dyad structure, we induced a positive synergy effect with the host moiety, enhancing OLED performance through intramolecular EnT.

Alzheimer's disease CSF biomarkers correlate with early pathology and alterations in neuronal and glial gene expression.

INTRODUCTION: Normal pressure hydrocephalus (NPH) patients undergoing cortical shunting frequently show early Alzheimer's disease (AD) pathology on cortical biopsy, which is predictive of progression to clinical AD. The objective of this study was to use samples from this cohort to identify cerebrospinal fluid  (CSF) biomarkers for AD-related central nervous system (CNS) pathophysiologic changes using tissue and fluids with early pathology, free of post mortem artifact. METHODS: We analyzed Simoa, proteomic, and metabolomic CSF data from 81 patients with previously documented pathologic and transcriptomic changes. RESULTS: AD pathology on biopsy correlates with CSF ß-amyloid-42/40, neurofilament light chain (NfL), and phospho-tau-181(p-tau181)/ß-amyloid-42, while several gene expression modules correlate with NfL. Proteomic analysis highlights seven core proteins that correlate with pathology and gene expression changes on biopsy, and metabolomic analysis of CSF identifies disease-relevant groups that correlate with biopsy data. DISCUSSION: As additional biomarkers are added to AD diagnostic panels, our work provides insight into the CNS pathophysiology these markers are tracking. HIGHLIGHTS: AD CSF biomarkers correlate with CNS pathology and transcriptomic changes. Seven proteins correlate with CNS pathology and gene expression changes. Inflammatory and neuronal gene expression changes correlate with YKL-40 and NPTXR, respectively. CSF metabolomic analysis identifies pathways that correlate with biopsy data. Fatty acid metabolic pathways correlate with ß-amyloid pathology.

Kojic acid reverses LPS-induced neuroinflammation and cognitive impairment by regulating the TLR4/NF-κB signaling pathway.

Intense neuroinflammation contributes to neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. Lipopolysaccharides (LPSs) are an integral part of the cell wall of Gram-negative bacteria that act as pathogen-associated molecular patterns (PAMPs) and potentially activate the central nervous system's (CNS) immune system. Microglial cells are the local macrophages of the CNS and have the potential to induce and control neuroinflammation. This study aims to evaluate the anti-inflammatory and antioxidant effect of kojic acid against the toxic effects of LPSs, such as neuroinflammation-induced neurodegeneration and cognitive decline. The C57BL/6N mice were subjected to LPS injection for 2 weeks on alternate days (each mouse received 0.25 mg/kg/i.p. for a total of seven doses), and kojic acid was administered orally for 3 weeks consecutively (50 mg/kg/mouse, p. o). Bacterial endotoxins, or LPSs, are directly attached to TLR4 surface receptors of microglia and astrocytes and alter the cellular metabolism of immune cells. Intraperitoneal injection of LPS triggers the toll-like receptor 4 (TLR4), phospho-nuclear factor kappa B (p-NFκB), and phospho-c-Jun n-terminal kinase (p-JNK) protein expressions in the LPS-treated group, but these expression levels were significantly downregulated in the LPS + KA-treated mice brains. Prolong neuroinflammation leads to the generation of reactive oxygen species (ROS) followed by a decrease in nuclear factor erythroid-2-related factor 2 (Nrf2) and the enzyme hemeoxygenase 1 (HO-1) expression in LPS-subjected mouse brains. Interestingly, the levels of both Nrf-2 and HO-1 increased in the LPS + KA-treated mice group. In addition, kojic acid inhibited LPS-induced TNF-α and IL-1ß production in mouse brains. These results indicated that kojic acid may suppress LPS-induced neuroinflammation and oxidative stress in male wild-type mice brains (in both the cortex and the hippocampus) by regulating the TLR4/NF-κB signaling pathway.

Hierarchical Chitin Nanocrystal-Based 3D Printed Dual-Layer Membranes Hydrogels: A Dual Drug Delivery Nano-Platform for Periodontal Tissue Regeneration.

Periodontitis, a prevalent chronic inflammatory disease caused by bacteria, poses a significant challenge to current treatments by merely slowing their progression. Herein, we propose an innovative solution in the form of hierarchical nanostructured 3D printed bilayer membranes that serve as dual-drug delivery nanoplatforms and provide scaffold function for the regeneration of periodontal tissue. Nanocomposite hydrogels were prepared by combining lipid nanoparticle-loaded grape seed extract and simvastatin, as well as chitin nanocrystals, which were then 3D printed into a bilayer membrane that possesses antimicrobial properties and multiscale porosity for periodontal tissue regeneration. The constructs exhibited excellent mechanical properties by adding chitin nanocrystals and provided a sustained release of distinct drugs over 24 days. We demonstrated that the bilayer membranes are cytocompatible and have the ability to induce bone-forming markers in human mesenchymal stem cells, while showing potent antibacterial activity against pathogens associated with periodontitis. In vivo studies further confirmed the efficacy of bilayer membranes in enhancing alveolar bone regeneration and reducing inflammation in a periodontal defect model. This approach suggests promising avenues for the development of implantable constructs that not only combat infections, but also promote the regeneration of periodontal tissue, providing valuable insights into advanced periodontitis treatment strategies.

In-stent Re-endothelialization Strategies: Cells, ECM, and Extracellular Vesicles.

Arterial stenosis caused by atherosclerosis often requires stent implantation to increase the patency of target artery. However, such external devices often lead to in-stent restenosis due to inadequate re-endothelialization and subsequent inflammatory responses. Therefore, re-endothelialization strategies after stent implantation have been developed to enhance endothelial cell recruitment or to capture circulating endothelial progenitor cells. Notably, recent research indicates that coating stent surfaces with biogenic materials enhances the long-term safety of implantation, markedly diminishing the risk of in-stent restenosis. In this review, we begin by describing the pathophysiology of coronary artery disease and in-stent restenosis. Then, we review the characteristics and materials of existing stents used in clinical practice. Lastly, we explore biogenic materials aimed at accelerating re-endothelialization, including extracellular matrix, cells, and extracellular vesicles. This review will help overcome the limitations of current stents for cardiovascular disease and outline the next phase of research and development.

Acid tolerance responses and their mechanisms in Lactiplantibacillus plantarum LM1001.

This study investigated the acid tolerance responses of Lactiplantibacillus plantarum LM1001 at physiological and molecular levels. Upon exposure to low pH, L. plantarum LM1001 demonstrated increased ATPase activity and ammonia consumption, which contributed to a higher intracellular pH. Comparative analysis of cell membrane fatty acids revealed that acid-stressed cells had a significantly higher proportion of unsaturated fatty acids than those of unstressed cells. There was differential upregulation of several genes, notably those involved in alkali production (arcB, argG, and argH) and in class I and class III stress responses (clpE, clpP, hrcA, dnaK, grpE, groEL, and groES). Following 2-h exposure to pH 2.5, L. plantarum LM1001 not only exhibited enhanced survival but also showed increased auto-aggregation and improved mucin adhesion capability, albeit with a reduction in hydrophobicity. These findings indicate that acid stress induces adaptive physiological and metabolic changes in L. plantarum LM1001, enhancing its acid resistance and adherence properties. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-024-01582-4.

The potential for drug incompatibility and its drivers - A hospital wide retrospective descriptive study.

OBJECTIVE: Drug incompatibility, a significant subset of medication errors, threaten patient safety during the medication administration phase. Despite the undeniably high prevalence of drug incompatibility, it is currently poorly understood because previous studies are focused predominantly on intensive care unit (ICU) settings. To enhance patient safety, it is crucial to expand our understanding of this issue from a comprehensive viewpoint. This study aims to investigate the prevalence and mechanism of drug incompatibility by analysing hospital-wide prescription and administration data. METHODS: This retrospective cross-sectional study, conducted at a tertiary academic hospital, included data extracted from the clinical data warehouse of the study institution on patients admitted between January 1, 2021, and May 31, 2021. Potential contacts in drug pairs (PCs) were identified using the study site clinical workflow. Drug incompatibility for each PC was determined by using a commercial drug incompatibility database, the Trissel's™ 2 Clinical Pharmaceutics Database (Trissel's 2 database). Drivers of drug incompatibility were identified, based on a descriptive analysis, after which, multivariate logistic regression was conducted to assess the risk factors for experiencing one or more drug incompatibilities during admission. RESULTS: Among 30,359 patients (representing 40,061 hospitalisations), 24,270 patients (32,912 hospitalisations) with 764,501 drug prescriptions (1,001,685 IV administrations) were analysed, after checking for eligibility. Based on the rule for determining PCs, 5,813,794 cases of PCs were identified. Among these, 25,108 (0.4 %) cases were incompatible PCs: 391 (1.6 %) PCs occurred during the prescription process and 24,717 (98.4 %) PCs during the administration process. By classifying these results, we identified the following drivers contributing to drug incompatibility: incorrect order factor; incorrect administration factor; and lack of related research. In multivariate analysis, the risk of encountering incompatible PCs was higher for patients who were male, older, with longer lengths of stay, with higher comorbidity, and admitted to medical ICUs. CONCLUSIONS: We comprehensively described the current state of drug incompatibility by analysing hospital-wide drug prescription and administration data. The results showed that drug incompatibility frequently occurs in clinical settings.

Retinal thickness and microvascular alterations observed by optical coherence tomography in antineutrophil cytoplasmic antibody-associated vasculitis: a cross-sectional study.

Background: As an autoimmune disease, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) often affects multiple organs, including the ocular system. This study aims to investigate differences in retinal thickness (RT) and retinal superficial vascular density (SVD) between patients with AAV and healthy controls (HCs) using optical coherence tomography angiography (OCTA). Currently, these differences are not clear. Methods: A total of 16 AAV individuals (32 eyes) and 16 HCs (32 eyes) were recruited to this cross-sectional study conducted in the First Affiliated Hospital of Nanchang University from June 2023 to September 2023. The study protocol conformed with the tenets of the Declaration of Helsinki (as revised in 2013). Each image observed by OCTA was divided into 9 regions using the Early Treatment Diabetic Retinopathy Study (ETDRS) subzones as a guide. Results: In the full layer, the RT of AAV patients was found to be significantly reduced in the inner superior (IS, P<0.001), outer superior (OS, P=0.003), inner temporal (IT, P=0.003), and outer temporal (OT, P<0.001) regions; inner RT was significantly lower in the IS (P=0.006), OS (P<0.001), inner nasal (IN, P=0.005), outer nasal (ON, P<0.001), and center (C, P=0.01) regions than that in HCs. Outer RT of AAV patients showed a reduction in the IS (P<0.001), as well as IT (P=0.008), and OT (P<0.001) regions. No statistically significant differences were seen in the different subregions in other different layers (P>0.05). Only the inner inferior (II) and outer inferior (OI) regions of SVD in AAV patients did not differ significantly from controls. All other regions showed a reduction in SVD. The details are as follows: IS (P<0.001), OS (P<0.001), IT (P=0.005), OT (P<0.001), IN (P<0.001), ON (P<0.001), and C (P=0.003). According to receiver operating characteristic (ROC) curve analysis, the full IS region [area under the curve (AUC): 0.8892, 95% confidence interval (CI): 0.8041-0.9742, P<0.001] had the highest diagnostic value for AAV-induced reduction in RT. The IS (AUC: 0.9121, 95% CI: 0.8322-0.9920, P<0.001) region was also the most sensitive to changes in SVD of AAV individuals. In addition, we found that SVD in the IN region (r=-0.4224, 95% CI: -0.6779 to -0.0757, P=0.02) as well as mean visual acuity (r=-0.3922, 95% CI: -0.6579 to -0.0397, P=0.03) of AAV patients were negatively correlated with disease duration. However, we did not find an association between SVD and RT in this study. Conclusions: The findings from OCTA indicated a reduction in RT and SVD among patients with AAV. OCTA allows for the evaluation of AAV-related ocular lesions and holds promise for monitoring of disease progression through regular evaluations.

Comparison of biportal endoscopic and microscopic tubular paraspinal approach for foraminal and extraforaminal lumbar disc herniation.

OBJECTIVE: Foraminal and extraforaminal lumbar disc herniation (FELDH) is an important pathological condition that can lead to lumbar radiculopathy. The paraspinal muscle-splitting approach introduced by Reulen and Wiltse is a reasonable surgical technique. Minimally invasive procedures using a tubular retractor system have also been introduced. However, surgical treatment is considered more challenging for FELDH than for central or subarticular lumbar disc herniations (LDHs). Some researchers have proposed uniportal extraforaminal endoscopic lumbar discectomy through a posterolateral approach as an alternative for FELDH, but heterogeneous clinical results have been reported. Recently, the biportal endoscopic (BE) paraspinal approach has been suggested as an alternative. The aim of this study was to compare the clinical outcomes of BE and microscopic tubular (MT) paraspinal approaches for decompressive foraminotomy and lumbar discectomy (paraLD) in patients with FELDH. METHODS: Ninety-one consecutive patients with unilateral lumbar radiculopathy and FELDH underwent paraLD. Demographic and perioperative data were collected. Clinical outcomes were evaluated using the visual analog scale (VAS) for back and leg pain, the Oswestry Disability Index (ODI) for spinal disability, and the modified Macnab criteria for patient satisfaction. Postoperative complications and reoperation rates were also evaluated. RESULTS: In total, 76 patients were included in the final analysis. Among them, 43 underwent BE paraLD (group A) and the remaining 33 underwent MT paraLD (group B). The demographic and preoperative data were not statistically different between the groups. All patients showed significant improvements in VAS back, VAS leg, and ODI scores compared with baseline values (p < 0.05). The improvement in VAS back scores was significantly better in group A than in group B on postoperative day 2 (p < 0.001). However, all clinical parameters were comparable between the two groups after postoperative year 1 (p > 0.05). According to the modified Macnab criteria, 86.1% and 72.7% of the patients had excellent or good outcomes in groups A and B, respectively. No intergroup differences were observed (p = 0.367). In addition, there were no differences in the total operation time or amount of surgical drainage. Postoperative complications were not significantly different between the two groups (p = 0.301); however, reoperation rates were significantly higher in group B (p = 0.035). CONCLUSIONS: BE paraLD is an effective treatment for FELDH and is an alternative to MT paraLD. In particular, BE paraLD has advantages of early improvement in postoperative back pain and low reoperation rates.