The emerging role of nitric oxide in the synaptic dysfunction of vascular dementia.

With an increase in global aging, the number of people affected by cerebrovascular diseases is also increasing, and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate. However, few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients. Similarly in Alzheimer's disease and other neurological disorders, synaptic dysfunction is recognized as the main reason for cognitive decline. Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system. Recently, nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia. This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction, neuroinflammation, oxidative stress, and blood-brain barrier dysfunction that underlie the progress of vascular dementia. Additionally, we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.

miRNA-21-5p is an important contributor to the promotion of injured peripheral nerve regeneration using hypoxia-pretreated bone marrow-derived neural crest cells.

JOURNAL/nrgr/04.03/01300535-202501000-00035/figure1/v/2024-05-14T021156Z/r/image-tiff Our previous study found that rat bone marrow-derived neural crest cells (acting as Schwann cell progenitors) have the potential to promote long-distance nerve repair. Cell-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular communication. Nevertheless, the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain unclear. To investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves, we collected conditioned culture medium from hypoxia-pretreated neural crest cells, and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose deprivation. The mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest cells. We performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest cells. Subsequently, to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons, we used a microfluidic axonal dissociation model of sensory neurons in vitro, and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons, which was greatly dependent on loaded miR-21-5p. Finally, we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb, as well as muscle tissue morphology of the hind limbs, were obviously restored. These findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in miRNA-21-5p. miRNA-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell secretome. This helps to explain the mechanism of action of the secretome and extracellular vesicles of neural crest cells in repairing damaged peripheral nerves, and also promotes the application of miR-21-5p in tissue engineering regeneration medicine.

Genome-wide identification of bZIP transcription factors in 12 Rosaceae species and modeling of novel mechanisms of EjbZIPs response to salt stress.

In plantae, basic leucine zipper (bZIP) transcription factors (TFs) are widespread and regulate a variety of biological processes under abiotic stress. However, it has not been extensively studied in Rosaceae, and the functional effects of bZIP on Eriobotrya japonica under salt stress are still unknown. Therefore, in this study, the bZIP TF family of 12 species of Rosaceae was analyzed by bioinformatics method, and the expression profile and quantitative real-time polymerase chain reaction of E. japonica under salt stress were analyzed. The results showed that a total of 869 bZIP TFs were identified in 12 species of Rosaceae and divided into nine subfamilies. Differences in promoter cis-elements between subfamilies vary depending on their role. Species belonging to the same subfamily have a similar number of chromosomes and the number of genes contained on each chromosome. Gene duplication analysis has found segmental duplication to be a prime force in the evolution of Rosaceae species. In addition, nine EjbZIPs were significantly different, including seven up-regulated and two down-regulated in E. japonica under salt stress. Especially, EjbZIP13 was involved in the expression of SA-responsive proteins by binding to the NPR1 gene. EjbZIP27, EjbZIP30, and EjbZIP38 were highly expressed in E. japonica under salt stress, thus improving the salt tolerance capacity of the plants. These results can provide a theoretical basis for exploring the characteristics and functions of the bZIP TF family in more species and breeding salt-tolerant E. japonica varieties. It also provides a reference for resolving the response mechanism of bZIP TF in 12 Rosaceae species under salt stress.

Clinical impact and role of major vessels involvement in laparoscopic resection for hepatic hemangioma.

BACKGROUND: Severe bleeding remains a significant concern in laparoscopic resection for hepatic hemangioma. It is rarely reported that how the degree of major vessels involvement impacts on severe bleeding. The present study primarily aimed to analyze the impacts of the number of involved major vessels (NIMV) during laparoscopic surgery for hepatic hemangioma and evaluate the risk factors associated with increased bleeding. METHODS: A database search was carried out for consecutive patients who underwent laparoscopic resection for liver hemangiomas at our department from January 2018 to December 2023. The collected data included demographics, characteristics of the hemangiomas, laboratory data, operation method, surgical and postoperative variables. RESULTS: A total of 72 patients were enrolled in the study. 42 patients were categorized into the group with NIMV < 2, while 30 patients were divided into the group with NIMV ≥ 2. The group with NIMV ≥ 2 demonstrated a significant correlation with special segments, involved multiple segments and diameter of the hemangiomas (P < 0.01). And the perioperative variables including the extent of resection, operative time, blood loss, Pringle maneuver times, postoperative stay, drainage tube duration, and postoperative liver function (ALT, AST) also showed significant differences between the two groups (P < 0.05). Notably, NIMV ≥ 2 was identified as the most important independent risk factor for intraoperative blood loss ≥ 500 ml in laparoscopic surgery for hepatic hemangioma (P = 0.011). For NIMV ≥ 2, the independent risk factor was special segments in multivariate analysis (P = 0.000). CONCLUSION: The involvement of multiple major vessels (NIMV ≥ 2) was significantly associated with special segments, resulting in increased intraoperative blood loss, operation difficulty, and delayed postoperative recovery. Moreover, it was identified as the single independent risk factor with a considerable risk for increased blood loss during laparoscopic resection for hepatic hemangioma.

Virtual Screening of GLP-1-Secreting Peptides from Pea Protein Hydrolysates via Peptide Transporter 1 (PepT1) Activation-Based Molecular Docking.

Dietary proteins regulate glucose homeostasis via intestinal protein sensing-induced glucagon-like peptide 1 (GLP-1) secretion. However, the reported GLP-1-secreting peptides derived from dietary proteins are few, and studies regarding GLP-1-secreting peptide identification by traditional separation and purification methods are laborious. Herein, we have rapidly virtual-screened two GLP-1 secreting peptides from pea protein hydrolysates (PPHs) by peptidomic analysis and molecular docking with peptide transporter 1 (PepT1). PPH-stimulated GLP-1 secretion decreased after adding the PepT1 antagonist 4-aminobenzoic acid (4-AMBA), indicating that PepT1 activation was involved in PPH-induced GLP-1 secretion in NCI-H716 cells. Subsequently, 307 tripeptides in PPHs were obtained through peptidomic analysis. Among them, two GLP-1-secreting peptides, FLR and LRW, were identified via PepT1 activation-based molecular docking. FLR and LRW (1 mg/mL) increased GLP-1 levels to 170.20% ± 27.83% and 272.37% ± 45.96%, respectively (p < 0.05). More importantly, molecular docking implied that the interactions between peptides and the active center of PepT1 (especially Glu595, Asn329, and Asn171 in the N-pocket and Arg27 in the C-pocket) were crucial for peptide activity in stimulating GLP-1 secretion. Our study suggested that the combination of peptidomics and PepT1 activation-based molecular docking is a promising approach for identification of GLP-1-secreting peptides.

The management pattern and outcomes of chronic thromboembolic pulmonary hypertension: rationale and design for a Chinese real-world study.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive pulmonary vascular disorder with substantial morbidity and mortality, also a disease underdiagnosed and undertreated. It is potentially curable by pulmonary endarterectomy (PEA) in patients with surgically accessible thrombi. Balloon pulmonary angioplasty (BPA) and targeted medical therapy are options for patients with distal lesions or persistent/recurrent pulmonary hypertension after PEA. There is an urgent need to increase the awareness of CTEPH. Qualified CTEPH centers are still quite limited. Baseline characteristics, management pattern and clinical outcome of CTEPH in China needs to be reported. METHODS AND DESIGN: The CHinese reAl-world study to iNvestigate the manaGEment pattern and outcomes of chronic thromboembolic pulmonary hypertension (CHANGE) study is designed to provide the multimodality treatment pattern and clinical outcomes of CTEPH in China. Consecutive patients who are ≥ 14 year-old and diagnosed with CTEPH are enrolled. The diagnosis of CTEPH is confirmed in right heart catheterization and imaging examinations. The multimodality therapeutic strategy, which consists of PEA, BPA and targeted medical therapy, is made by a multidisciplinary team. The blood sample and tissue from PEA are stored in the central biobank for further research. The patients receive regular follow-up every 3 or 6 months for at least 3 years. The primary outcomes include all-cause mortality and changes in functional and hemodynamic parameters from baseline. The secondary outcomes include the proportion of patients experiencing lung transplantation, the proportion of patients experiencing heart and lung transplantation, and changes in health-related quality of life. Up to 31 December 2023, the study has enrolled 1500 eligible patients from 18 expert centers. CONCLUSIONS: As a real-world study, the CHANGE study is expected to increase our understanding of CTEPH, and to fill the gap between guidelines and the clinical practice in the diagnosis, assessment and treatment of patients with CTEPH. REGISTRATION NUMBER IN CLINICALTRIALS.GOV: NCT05311072.

Autoclaving-treated germinated brown rice relieves hyperlipidemia by modulating gut microbiota in humans.

Introduction: Germinated brown rice is a functional food with a promising potential for alleviating metabolic diseases. This study aimed to explore the hypolipidemic effects of autoclaving-treated germinated brown rice (AGBR) and the underlying mechanisms involving gut microbiota. Methods: Dietary intervention with AGBR or polished rice (PR) was implemented in patients with hyperlipidemia for 3 months, and blood lipids were analyzed. Nutritional characteristics of AGBR and PR were measured and compared. Additionally, 16S rDNA sequencing was performed to reveal the differences in gut microbiota between the AGBR and PR groups. Results: AGBR relieves hyperlipidemia in patients, as evidenced by reduced levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein-B, and elevated levels of high-density lipoprotein cholesterol and apolipoprotein-A1. In terms of nutrition, AGBR had significantly higher concentrations of free amino acids (10/16 species), γ-aminobutyric acid, resistant starch, soluble dietary fiber, and flavonoids (11/13 species) than PR. In addition, higher microbial abundance, diversity, and uniformity were observed in the AGBR group than in the PR group. At the phylum level, AGBR reduced Firmicutes, Proteobacteria, Desulfobacterota, and Synergistota, and elevated Bacteroidota and Verrucomicrobiota. At the genus level, AGBR elevated Bacteroides, Faecalibacterium, Dialister, Prevotella, and Bifidobacterium, and reduced Escherichia-Shigella, Blautia, Romboutsia, and Turicibacter. Discussion: AGBR contributes to the remission of hyperlipidemia by modulating the gut microbiota.

Synergistic effect of gellan gum and guar gum on improving the foaming properties of soy protein isolate-based complexes: Interaction mechanism and interfacial behavior.

Interactions among multi-component play a critical role in modulating the foaming properties of aerated foods. This study evaluated the mechanisms of synergistic improvement of gellan gum (GEG) and guar gum (GUG) on the foaming properties of soy protein isolate (SPI)-based complex. The results showed that the GEG/GUG ratio was closely related to the intermolecular interactions of SPI-based ternary complex and the dynamical changing of its foaming properties. The SPI/GEG/GUG ternary complex with a GEG/GUG ratio of 2/3 exhibited the highest foamability (195 %) and comparable foam stability (99.17 %), which were 32.95 % and 2.99 % higher than that of SPI/GEG binary complex. At this ratio, GUG promoted the interactions between SPI and GEG, and bound to complex's surface through hydrogen bonding, resulting in the increase of particle size and surface charge, and the decrease of surface hydrophobicity. Although this reduced the diffusion of complex onto the air/water interface, it increased permeation rate and molecular rearrangement behavior, which were the potential mechanisms to improve the foaming properties. Additionally, the synergistic effect of GEG and GUG also enhanced the elastic strength and solid characteristics of foam systems. This study provided a theoretical guidance for the targeted modulation of foaming properties of multi-component aerated foods.

Disturbance in cerebral blood microcirculation and hypoxic-ischemic microenvironment are associated with the development of brain metastasis.

Brain metastases (BM) constitute an increasing challenge in oncology due to their impact on neurological function, limited treatment options, and poor prognosis. BM occur through extravasation of circulating tumor cells across the blood-brain barrier. However, the extravasation processes are still poorly understood. We here propose a brain colonization process which mimics infarction-like microenvironmental reactions, that is dependent on Angiopoietin (Ang-2) and vascular endothelial growth factor (VEGF). In this study, intracardiac BM models were used, and cerebral blood microcirculation was monitored by 2-photon microscopy through a cranial window. BM formation was observed using cranial magnetic resonance, bioluminescent imaging, and post-mortem autopsy. Ang-2/VEGF targeting strategies and Ang-2 gain-of-function (GOF) mice were employed to interfere with BM formation. In addition, vascular and stromal factors as well as clinical outcome were analyzed in BM patients. Blood vessel occlusions by cancer cells were detected, accompanied by significant disturbances of cerebral blood microcirculation, and focal stroke-like histological signs. Cerebral endothelial cells showed an elevated Ang-2 expression both in mouse and human BM. Ang-2 GOF resulted in an increased BM burden. Combined anti-Ang-2/anti-VEGF therapy led to a decrease in brain metastasis size and number. Ang-2 expression in tumor vessels of established human brain metastases negatively correlated with survival. Our observations revealed a relationship between disturbance of cerebral blood microcirculation and brain metastasis formation. This suggests that vessel occlusion by tumor cells facilitates brain metastatic extravasation and seeding, while combined inhibition of microenvironmental effects of Ang-2 and VEGF prevent the outgrowth of macrometastases.

A review of the extraction and purification methods, biological activities, and applications of active compounds in Acanthopanax senticosus.

Acanthopanax senticosus (AS) is a geo-authentic crude medicinal plant that grows in China, Korea, Russia, and Japan. AS contains bioactive compounds such as eleutherosides, polysaccharides, and flavonoids. It is also a key traditional herb in the Red List of Chinese Species. AS is mainly distributed in Northeast China, specifically in Heilongjiang, Jilin, and Liaoning provinces. Its active compounds contribute to significant biological activities, including neuroprotective, antioxidant, anti-fatigue, and antitumor effects. However, the extraction methods of active compounds are complex, the extraction efficiency is poor, and the structure-activity relationship is unclear. This study focused on the nutrients in AS, including protein, carbohydrates, and lipids. Particularly, the active ingredients (eleutherosides, polysaccharides, and flavonoids) in AS and their extraction and purification methods were analyzed and summarized. The biological activities of extracts have been reviewed, and the mechanisms of anti-oxidation, antitumor, anti-inflammation, and other activities are introduced in detail. The applications of AS in various domains, such as health foods, medicines, and animal dietary supplements, are then reported. Compared with other extraction methods, ultrasonic or microwave extraction improves efficiency, yet they can damage structures. Challenges arise in the recovery of solvents and in achieving extraction efficiency when using green solvents, such as deep eutectic solvents. Improvements can be made by combining extraction methods and controlling conditions (power, temperature, and time). Bioactive molecules and related activities are exposited clearly. The applications of AS have not been widely popularized, and the corresponding functions require further development.

Associations of dietary flavonoid intake with the risk of all-cause and cardiovascular mortality in adults.

BACKGROUND AND AIMS: Flavonoids are widely distributed polyphenolic compounds in the diet that possess various health-promoting effects. This study aimed to investigate the association between dietary flavonoid intake and all-cause and cardiovascular mortality in adults. METHODS AND RESULTS: The data on the six main subclasses of flavonoids, including isoflavones, anthocyanidins, flavan-3-ols, flavanones, flavones, and flavonols, were obtained from the 2007-2010 National Health and Nutrition Examination Survey (NHANES) dataset of adults. The participants were followed up until December 30, 2019. Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for dietary flavonoid intake and mortality. The study included a total of 8758 adults (mean age 44.00 years; 47.40% men). A median follow-up of 10.7 years yielded 1113 all-cause deaths and 261 cardiovascular deaths were recorded. In comparison to category 1, category 4 of flavan-3-ols, flavonols, and total flavonoids were associated with lower risks of all-cause mortality, with multivariable-adjusted HRs of 0.71 (95% CI: 0.55-0.92, Ptrend = 0.021), 0.58 (95% CI: 0.45-0.74, Ptrend<0.001), and 0.63 (95% CI: 0.50-0.80, Ptrend = 0.010), respectively. Similarly, higher intake of category 4 flavonoids was associated with a reduced risk of cardiovascular mortality, with HRs of 0.68 (95% CI: 0.29-0.89, Ptrend = 0.035) for flavones, 0.41 (95% CI: 0.22-0.78, Ptrend = 0.001) for flavonols, and 0.54 (95% CI: 0.36-0.80, Ptrend = 0.021) for total flavonoids. CONCLUSION: Dietary flavonoid intake is associated with all-cause and cardiovascular mortality. Increasing dietary flavonoid intake may reduce the risk of death in adults.

Performance of continuous glucose monitoring in patients with acute respiratory failure: a prospective, single-center observational study.

OBJECTIVE: Continuous glucose monitoring (CGM) may have benefits in achieving glycemic control in critically ill patients. The aim of this study was to assess the accuracy of the Freestyle Libre H (professional version of the Libre Pro). in patients with acute respiratory failure (ARF) in the intensive care unit (ICU). METHODS: 52 adult patients with ARF were selected. The performance of CGM was evaluated using arterial blood glucose (aBG) and point-of-care (POC) glucose as reference values. Numerical accuracy was evaluated by the mean absolute relative difference (MARD), Bland-Altman analysis, and %15/15(the percentage of CGM values within 15 mg/dL or 15% of reference values <100 mg/dL or >100mg/dL, respectively), %20/20 and %30/30; Clinical accuracy was assessed by Clarke error grid analysis. RESULTS: 519 and 1504 pairs of aBG/CGM and POC/CGM glucose values were analyzed. The MARD values were 13.8% and 14.7%, respectively. The mean deviation of the Bland‒Altman analysis was 0.82 mmol/L and 0.81 mmol/L. %15/15, %20/20 and %30/30 of aBG values were 62.6%, 75.5%, and 92.4%, respectively; %15/15, %20/20 and %30/30 of POC values were 57.1%, 72.9%, and 88.7%, respectively. The Clarke error grid analysis showed that 97.8% and 99.3% of the values located in the (A+B) zone. Additionally, accuracy of CGM is not affected by general patient factors. CONCLUSION: This study demonstrated that the accuracy of CGM in patients with ARF is lower than that in most outpatients, and it is not affected by general patient factors. Whether CGM is beneficial to glucose management in ICU needs further evaluation.

Association analyses of apolipoprotein E genotypes and cognitive performance in patients with Parkinson's disease.

BACKGROUND: Cognitive impairment is a common non-motor symptom of Parkinson's disease (PD). The apolipoprotein E (APOE) ε4 genotype increases the risk of Alzheimer's disease (AD). However, the effect of APOEε4 on cognitive function of PD patients remains unclear. In this study, we aimed to understand whether and how carrying APOEε4 affects cognitive performance in patients with early-stage and advanced PD. METHODS: A total of 119 Chinese early-stage PD patients were recruited. Movement Disorder Society Unified Parkinson's Disease Rating Scale, Hamilton anxiety scale, Hamilton depression scale, non-motor symptoms scale, Mini-mental State Examination, Montreal Cognitive Assessment, and Fazekas scale were evaluated. APOE genotypes were determined by polymerase chain reactions and direct sequencing. Demographic and clinical information of 521 early-stage and 262 advanced PD patients were obtained from Parkinson's Progression Marker Initiative (PPMI). RESULTS: No significant difference in cognitive performance was found between ApoEε4 carriers and non-carriers in early-stage PD patients from our cohort and PPMI. The cerebrospinal fluid (CSF) Amyloid Beta 42 (Aß42) level was significantly lower in ApoEε4 carrier than non-carriers in early-stage PD patients from PPMI. In advanced PD patients from PPMI, the BJLOT, HVLT retention and SDMT scores seem to be lower in ApoEε4 carriers without reach the statistical significance. CONCLUSIONS: APOEε4 carriage does not affect the cognitive performance of early-stage PD patients. However, it may promote the decline of CSF Aß42 level and the associated amyloidopathy, which is likely to further contribute to the cognitive dysfunction of PD patients in the advanced stage.

Using machine learning to develop preoperative model for lymph node metastasis in patients with bladder urothelial carcinoma.

BACKGROUND: Lymph node metastasis (LNM) is associated with worse prognosis in bladder urothelial carcinoma (BUC) patients. This study aimed to develop and validate machine learning (ML) models to preoperatively predict LNM in BUC patients treated with radical cystectomy (RC). METHODS: We retrospectively collected demographic, pathological, imaging, and laboratory information of BUC patients who underwent RC and bilateral lymphadenectomy in our institution. Patients were randomly categorized into training set and testing set. Five ML algorithms were utilized to establish prediction models. The performance of each model was assessed by the area under the receiver operating characteristic curve (AUC) and accuracy. Finally, we calculated the corresponding variable coefficients based on the optimal model to reveal the contribution of each variable to LNM. RESULTS: A total of 524 and 131 BUC patients were finally enrolled into training set and testing set, respectively. We identified that the support vector machine (SVM) model had the best prediction ability with an AUC of 0.934 (95% confidence interval [CI]: 0.903-0.964) and accuracy of 0.916 in the training set, and an AUC of 0.855 (95%CI: 0.777-0.933) and accuracy of 0.809 in the testing set. The SVM model contained 14 predictors, and positive lymph node in imaging contributed the most to the prediction of LNM in BUC patients. CONCLUSIONS: We developed and validated the ML models to preoperatively predict LNM in BUC patients treated with RC, and identified that the SVM model with 14 variables had the best performance and high levels of clinical applicability.

Promotive effect of skin precursor-derived Schwann cells on brachial plexus neurotomy and motor neuron damage repair through milieu-regulating secretome.

Brachial plexus injury (BPI) with motor neurons (MNs) damage still remain poor recovery in preclinical research and clinical therapy, while cell-based therapy approaches emerged as novel strategies. Previous work of rat skin precursor-derived Schwann cells (SKP-SCs) provided substantial foundation for repairing peripheral nerve injury (PNI). Given that, our present work focused on exploring the repair efficacy and possible mechanisms of SKP-SCs implantation on rat BPI combined with neurorrhaphy post-neurotomy. Results indicated the significant locomotive and sensory function recovery, with improved morphological remodeling of regenerated nerves and angiogenesis, as well as amelioration of target muscles atrophy and motor endplate degeneration. Besides, MNs could restore from oxygen-glucose-deprivation (OGD) injury upon SKP-SCs-sourced secretome treatment, implying the underlying paracrine mechanisms. Moreover, rat cytokine array assay detected 67 cytokines from SKP-SC-secretome, and bioinformatic analyses of screened 32 cytokines presented multiple functional clusters covering diverse cell types, including inflammatory cells, Schwann cells, vascular endothelial cells (VECs), neurons, and SKP-SCs themselves, relating distinct biological processes to nerve regeneration. Especially, a panel of hypoxia-responsive cytokines (HRCK), can participate into multicellular biological process regulation for permissive regeneration milieu, which underscored the benefits of SKP-SCs and sourced secretome, facilitating the chorus of nerve regenerative microenvironment. Furthermore, platelet-derived growth factor-AA (PDGF-AA) and vascular endothelial growth factor-A (VEGF-A) were outstanding cytokines involved with nerve regenerative microenvironment regulating, with significantly elevated mRNA expression level in hypoxia-responsive SKP-SCs. Altogether, through recapitulating the implanted SKP-SCs and derived secretome as niche sensor and paracrine transmitters respectively, HRCK would be further excavated as molecular underpinning of the neural recuperative mechanizations for efficient cell therapy; meanwhile, the analysis paradigm in this study validated and anticipated the actions and mechanisms of SKP-SCs on traumatic BPI repair, and was beneficial to identify promising bioactive molecule cocktail and signaling targets for cell-free therapy strategy on neural repair and regeneration.

Evaluation of the safety and efficacy of the novel Mycoplasma gallisepticum vaccine, Vaxsafe MG304, after spray-vaccination of 1-day-old specific pathogen-free chicks.

Mycoplasma gallisepticum causes chronic respiratory disease in poultry. A novel vaccine, Vaxsafe MG304 (the ts-304 strain), has greater protective efficacy in chickens than the Vaxsafe MG (strain ts-11) vaccine when delivered by eye drop at 3 weeks of age. Applying this vaccine in the hatchery to 1-day-old birds, using mass administration methods, would improve animal welfare and reduce labour costs associated with handling individual birds. This study assessed the protection provided by vaccination with Vaxsafe MG304 after administration to 1-day-old chicks. Chicks were administered a single dose of the vaccine to assess the efficacy of either a high dose (107.0 colour changing units, CCU) or a low dose (105.7 CCU) after eye drop or spray (in water or gel) administration against experimental challenge with virulent M. gallisepticum strain Ap3AS at 7 weeks of age. The vaccine was able to colonise the palatine cleft of chicks after vaccination by eye drop (at both doses) or by spray (in water or gel) (at the high dose). The high dose of vaccine, when delivered by eye drop or spray, was shown to be safe and induced a serological response and protective immunity (as measured by tracheal mucosal thickness and air sac lesion scores) against challenge. Vaccination of 1-day-old chicks with Vaxsafe MG304 by eye drop induced protective immunity equivalent to vaccination at 3 weeks of age. Vaxsafe MG304 was also protective when applied by both coarse- and gel spray methods at the higher dose and is therefore a suitable live attenuated vaccine for use in 1-day-old chicks.

Dexmedetomidine use during orthotopic liver transplantation surgery on early allograft dysfunction: A randomized controlled trial.

BACKGROUND: Previous studies have shown a protective effect of dexmedetomidine use in kidney transplantation. In contrast, it is not known whether intraoperative administration of dexmedetomidine can reduce early allograft dysfunction incidence following liver transplantation. OBJECTIVE: To investigate the effect of dexmedetomidine use during surgery on early allograft dysfunction following orthotopic liver transplantation (OLT). STUDY DESIGN: This is a single-center, double-blinded, placebo-controlled randomized clinical trial. 330 adult patients undergoing orthotopic liver transplantation were enrolled from Jan 14th, 2019 to May 22nd, 2022. Patients received dexmedetomidine or normal saline during surgery. 1 year follow-ups were recorded. METHODS: Patients were randomized to two groups receiving either dexmedetomidine or normal saline intraoperatively. For patients in the dexmedetomidine group, a loading dose (1 µg/kg over 10 min) of dexmedetomidine was given after induction of anesthesia followed by a continuous infusion (0.5 µg/kg /h) until the end of surgery. For patients in the normal saline group, an equal volume loading dose of 0.9% saline was given after the induction of anesthesia followed by an equal volume continuous infusion until the end of surgery. The primary outcome was early allograft dysfunction. Secondary outcomes included primary graft non-function, acute kidney injury and acute lung injury/ acute respiratory distress syndrome. RESULTS: Of 330 patients included in the intention-to-treat analysis, 165 were in the dexmedetomidine group (mean [SD] age, 49 [10] years; 117 [70.9%] men), and 165 were in the normal saline group (mean SD age, 49 [9] years; 118 [74%] men). 39 (24.4%) patients in the dexmedetomidine group and 31 (19.4%) in normal saline group developed early allograft dysfunction and the difference was statistically insignificant (P=0.28). Secondary outcomes including primary graft non-function and acute kidney injury was similar between the two groups. CONCLUSION: Intraoperative administration of dexmedetomidine did not reduce early allograft dysfunction rate after orthotopic liver transplantation.

Comparison of Effects of Propofol Combined with Different Doses of Esketamine for ECT in the Treatment of Depression: A Randomized Controlled Trial Protocol.

Objective: Major depressive disorder (MDD) is a common mood disorder. Electroconvulsive therapy (ECT) has a significant effect on treatment-resistant MDD. Esketamine may have potential advantages in improving the efficacy of ECT, and the strong affinity of this compound for NMDAR renders it a viable therapeutic option for the management of depression. This study aims to compare the effects of different doses of esketamine combined with propofol anesthesia versus propofol anesthesia alone in ECT, aiming to provide further insights for optimizing ECT and enhancing comprehensive treatment outcomes for depression. Study Design and Methods: This study was a prospective, randomized, controlled, double-blind trial involving subjects and evaluators. One hundred eleven patients scheduled for ECT were randomly assigned to three groups. In Group P, propofol at 1mg/kg was administered intravenously. In Group P+E, propofol at a dosage of 0.5mg/kg and esketamine at a dosage of 0.5mg/kg was administered intravenously. Patients in Group P+SE received propofol at a dosage of 0.75mg/kg and esketamine at a dosage of 0.25mg/kg. The same anesthesia protocol was used for the same patient until the end of the last treatment. The primary outcome measures were the Hamilton depression scale (HAMD) and the Patient Health Questionnaire-9 (PHQ-9), the Columbia-Suicide Severity Rating Scale (C-SSRS), and the Digit symbol substitution test (DSST). Secondary outcomes included length of hospital stay, readmission rate, hemodynamic status, recovery, and adverse events. Discussion: This study aimed to compare the effects of propofol combined with different doses of esketamine for ECT. The results may provide a better choice for ECT anesthesia.