Aided Porous Medium Emulsification for Functional Hydrogel Microparticles Synthesis.

Despite the substantial advancement in developing various hydrogel microparticle (HMP) synthesis methods, emulsification through porous medium to synthesize functional hybrid protein-polymer HMPs has yet to be addressed. Here, the aided porous medium emulsification for hydrogel microparticle synthesis (APME-HMS) system, an innovative approach drawing inspiration from porous medium emulsification is introduced. This method capitalizes on emulsifying immiscible phases within a 3D porous structure for optimal HMP production. Using the APME-HMS system, synthesized responsive bovine serum albumin (BSA) and polyethylene glycol diacrylate (PEGDA) HMPs of various sizes are successfully synthesized. Preserving protein structural integrity and functionality enable the formation of cytochrome c (cyt c) - PEGDA HMPs for hydrogen peroxide (H2O2) detection at various concentrations. The flexibility of the APME-HMS system is demonstrated by its ability to efficiently synthesize HMPs using low volumes (≈50 µL) and concentrations (100 µm) of proteins within minutes while preserving proteins' structural and functional properties. Additionally, the capability of the APME-HMS method to produce a diverse array of HMP types enriches the palette of HMP fabrication techniques, presenting it as a cost-effective, biocompatible, and scalable alternative for various biomedical applications, such as controlled drug delivery, 3D printing bio-inks, biosensing devices, with potential implications even in culinary applications.

Surgical treatment for medium-sized cystic osteochondral lesions of the talus: Autologous osteoperiosteal transplantation provides better clinical outcomes than bone marrow stimulation when cysts are deeper than 6 mm.

PURPOSE: To compare clinical outcomes of autologous osteoperiosteal transplantation versus bone marrow stimulation (BMS) for medium-sized (100-150 mm2) cystic osteochondral lesions of the talus (OLTs) and assess the correlation between patient demographics and outcomes. It was hypothesised that autologous osteoperiosteal transplantation would provide better clinical outcomes than BMS for medium-sized cystic OLTs. METHODS: Patients who underwent autologous osteoperiosteal transplantation or BMS for medium-sized cystic OLTs between 2014 and 2019 were retrospectively evaluated. According to their characteristics, a 1:1 propensity-score matching was performed and 33 pairs of patients were matched. The visual analogue scale, American Orthopaedic Foot and Ankle Society (AOFAS) score, Foot Ankle Outcome Score (FAOS) and Ankle Activity Score were collected preoperatively and at the last follow-up. In addition, a general linear model analysis was performed between patient demographics and clinical outcomes in two groups separately to detect potential risk factors. RESULTS: Finally, 28 patients in the grafted group and 27 patients in the BMS group completed the follow-up and were enrolled with a mean follow-up period of 63.5 ± 13.9 months. Both groups showed significant improvement in all patient-reported outcomes (p < 0.01). At the final follow-up, no significant differences between groups were found in all postoperative scores except FAOS Pain (p = 0.02). Correlation analysis showed a moderate correlation between cyst depth and the postoperative AOFAS score in the BMS group (r = -0.48, p = 0.01). Based on the regression line, the patients in the BMS group with a cyst deeper than 6 mm showed a lower AOFAS score than the mean score (88.7 ± 9.5) of the grafted group. CONCLUSION: Autologous osteoperiosteal transplantation and BMS are both safe and effective for medium-sized cystic OLTs. However, autologous osteoperiosteal transplantation is expected to provide better clinical outcomes than BMS when the cysts are deeper than 6 mm. LEVEL OF EVIDENCE: Level III.

Pharmacokinetics of aspirin: evaluating shortcomings in the literature.

INTRODUCTION: Aspirin is known for its therapeutic benefits in preventing strokes and relieving pain. However, it is toxic to some individuals, and the biological mechanisms causing toxicity are unknown. Limited literature is available on the role of glycine conjugation as the principal pathway in aspirin detoxification. Previous studies have quantified this two-step enzyme reaction as a singular enzymatic process. Consequently, the individual contributions of these enzymes to the kinetics remain unclear. AREAS COVERED: This review summarized the available information on the pharmacokinetics and detoxification of aspirin by the glycine conjugation pathway. Literature searches were conducted using Google Scholar and the academic journal databases accessible through the North-West University Library. Furthermore, the factors affecting interindividual variation in aspirin metabolism and what is known regarding aspirin toxicity were discussed. EXPERT OPINION: The greatest drawback in understanding the pharmacokinetics of aspirin is the limited information available on the substrate preference of the xenobiotic ligase (ACSM) responsible for activating salicylate to salicyl-CoA. Furthermore, previous pharmacokinetic studies did not consider the contribution of other substrates from the diet or genetic variants, to the detoxification rate of glycine conjugation. Impaired glycine conjugation might contribute to adverse health effects seen in Reye's syndrome and cancer.

Using a genetic backpropagation neural network model for credit risk assessment in the micro, small and medium-sized enterprises.

In China, with the "Double Carbon" goal within reach, Micro, Small and Medium-sized Enterprises (MSMEs) emerge as pivotal contributors to economic advancement. However, they are now confronted with the imperative of transitioning towards green and low-carbon practices. To facilitate the attainment of peak carbon dioxide emissions and carbon neutrality, a refined approach is imperative. This entails precise capital allocation, enhanced financial services, streamlined management, and robust risk mitigation strategies. Consequently, conducting thorough credit risk assessments for MSMEs becomes a crucial endeavor. However, obtaining substantial loans for them proves challenging due to their elusive credit ratings and potential defaults. To address this issue, this study leverages machine learning and intelligent optimization algorithms to construct a classification model for default and credit ratings of MSMEs, utilizing their daily invoice data. Specifically, twelve indicators pertaining to default and credit ratings are extracted. Subsequently, Principal Component Analysis is employed to reduce dimensionality and synthesize all pertinent information. Following this, the Genetic Algorithm-based Back Propagation Neural Network (GA-BPNN) is utilized to delineate the relationship between indicators and default, as well as credit rating, respectively. The results indicate a prediction accuracy of 0.92 for default risk and 0.86 for credit rating. This underscores the efficacy of GA-BPNN in effectively classifying the underlying default risk and credit ratings of MSMEs, offering a promising approach for decision-making.

Benefits and functionality of an interorganisational workplace health management network - insights from the companies' perspective.

Introduction: Workplace health management (WHM) is a worthwhile investment for companies. Nevertheless, the implementation of health-promoting interventions remains limited, especially in small and medium-sized enterprises. Interorganisational networks could be a promising way to raise awareness of the advantages of implementing WHM. Therefore, the aim of this study is to analyse the perceived functionality and benefits of a regional WHM network from companies' perspective and to present initial results on this specific topic. Methods: An explorative qualitative case study was conducted analysing ERZgesund, a WHM network in a rural region in Germany. Twenty-two companies that participated in the network were interviewed about their experiences and perceived advantages and disadvantages participating in the WHM network ERZgesund. Results: The findings show that the network has raised awareness about WHM among the companies, provides opportunities for exchange of knowledge and experiences, and generates or strengthens collaboration. The positive effects were enhanced by the network's structure, such as regionality and a direct contact person. Nevertheless, some companies stated that they would welcome a higher level of participation and transparency. Conclusion: Overall, it becomes clear that a WHM network can be a valuable tool to emphasize the relevance of WHM to companies. Therefore, further studies should validate and intensify the research on WHM networks to ensure a long-term benefit from the network.

Chemical gasification: An alternative approach to in vitro maturation of bovine oocytes.

This study aimed to evaluate the effect of chemical gasification and HEPES as alternative systems to pH control during in vitro maturation on bovine oocytes competence. Groups of 20 bovine cumulus oocytes complexes (COCs) were randomly distributed and cultured for 24 h in one of the following experimental groups: (i) chemical reaction (ChRG) system: CO2 generated from sodium bicarbonate and citric acid reaction (ii) culture media TCM-HEPES (HEPES-G); and (iii) control group (CNTG) in conventional incubator. After in vitro maturation (IVM), the COCs were in vitro fertilized (IVF), and in vitro cultivated (IVC) in a conventional incubator. We evaluated oocyte nuclear maturation, cleavage and blastocyst rates, in addition to the relative mRNA expression of BAX, BMP-15, AREG and EREG genes in oocytes and cumulus cells. The proportion of oocytes in metaphase II was higher in CNTG and ChRG (77.57% and 77.06%) than in the HEPES-G (65.32%; p = .0408 and .0492, respectively). The blastocyst production was similar between CNTG and ChRG (26.20% and 28.47%; p = .4232) and lower (p = .001) in the HEPES-G (18.71%). The relative mRNA expression of BAX gene in cumulus cells was significantly higher (p = .0190) in the HEPES-G compared to the CNTG. Additionally, the relative mRNA expression of BMP-15 gene was lower (p = .03) in oocytes from HEPES-G compared to the CNTG. In conclusion, inadequate atmosphere control has a detrimental effect on oocyte maturation. Yet, the use of chemical gasification can be an efficient alternative to bovine COCs cultivation.

Degree of subarachnoid hemorrhage affects clinical outcome after mechanical thrombectomy for M2 occlusion.

PURPOSE: The prognostic relevance of post-mechanical thrombectomy (MT) subarachnoid hemorrhage (SAH) remains controversial. This study aimed to investigate whether the thickness of the SAH clot affects clinical outcomes following MT for M2 occlusion. METHODS: A retrospective analysis was conducted on a prospective database of patients who underwent MT for isolated M2 occlusion. Patients were categorized into three groups based on the presence and thickness of SAH. Clinical and angiographical characteristics and outcomes were compared. RESULTS: Of the 36 patients included, SAH was observed in 15 (42%). When comparing patients with no SAH (grade 0) or thin SAH (grade 1) (N = 28) with those who had thick SAH (grade 2) (N = 8), patients with Grade 2 SAH required a higher number of passes and had a more severe angulation at M2. Patients with SAH Grade 2 had significantly worse NIHSS scores at 24 h (median, 4 vs. 14), but only one patient was identified as having a symptomatic intracranial hemorrhage. Patients with SAH Grade 2 were found to have a lower rate of favorable outcome (modified Rankin scale 0-2) (23% vs. 75%, P = 0.0026) and higher mortality (25% vs. 0%, P = 0.0499) at 90 days. CONCLUSION: The study found that thick SAH prevents clinical recovery after MT for M2 occlusion, even in cases of successful recanalization, and is associated with an unfavorable outcome. Thick SAH after MT is also linked to an increase in the number of passes and severe angulation at the M2 segment.

Sustained fentanyl exposure inhibits neuronal activity in dissociated striatal neuronal-glial co-cultures through actions independent of opioid receptors.

Besides having high potency and efficacy at the µ- (MOR) and other opioid receptor types, fentanyl has some affinity for some adrenergic receptor types, which may underlie its unique pathophysiological differences from typical opioids. To better understand the unique actions of fentanyl, we assessed the extent to which fentanyl alters striatal medium spiny neuronal (MSNs) activity via opioid or α1 adrenoceptors in dopamine type 1 or type 2 receptor- (D1 or D2) -expressing MSNs. In neuronal and mixed-glial co-cultures from the striatum, acute fentanyl (100 nM) exposure decreased the frequency of spontaneous action potentials. Overnight exposure of co-cultures to 100 nM fentanyl severely reduced the proportion of MSNs with spontaneous action potentials, which was unaffected by co-exposure to the opioid receptor antagonist naloxone (10 µM), but fully negated by co-administering the pan-α1 adrenoceptor inverse agonist prazosin (100 nM) and partially reversed by the selective α1A/C adrenoceptor antagonist RS 100329 (300 nM). Acute fentanyl (100 nM) exposure modestly reduced the frequency of action potentials and caused firing rate adaptations in D2, but not D1, MSNs. Prolonged (2-5 h) fentanyl (100 nM) application dramatically attenuated firing rates in both D1 and D2 MSNs. To identify possible cellular sites of α1 adrenoceptor action, α1 adrenoceptors were localized in subpopulations of striatal astroglia and neurons by immunocytochemistry, and Adra1a mRNA by in situ hybridization in astrocytes. Thus, sustained fentanyl exposure can inhibit striatal MSN activity via a non-opioid receptor-dependent pathway, that may be modulated via complex actions in α1 adrenoceptor-expressing striatal neurons and/or glia.

Optimizing thrombectomy in medium vessel occlusion: Focus on vessel diameter.

OBJECTIVES: Mechanical thrombectomy for medium vessel occlusion (MeVO) is a challenging field with limited results. In this study, we aimed at evaluating the efficacy and safety of a procedural strategy beginning with occluded vessel diameter measurement and matched aspiration catheter selection. MATERIALS AND METHODS: We retrospectively analyzed all sequentially treated patients by mechanical thrombectomy at two comprehensive stroke centers between May 2020 and April 2023, focusing on the occluded vessel diameter. We included patients who underwent thrombectomy for MeVO based on the matching strategy (a procedural approach involving vessel diameter assessment, matching aspiration catheter selection, and firm clot engagement with or without a stent retriever). We evaluated efficacy and safety using the modified Thrombolysis in the Cerebral Infarction Scale (mTICI) and intracranial hemorrhage (ICH) and procedure-related complications. RESULTS: Seventy patients fulfilled the final inclusion criteria. The median occluded vessel diameter was 1.71 mm. We achieved mTICI 2b/2c/3 in 82.9% and mTICI 2c/3 in 51.4% of the cases and did not observe any symptomatic ICH. We detected asymptomatic subarachnoid hemorrhage (SAH) in 24.3% of the cases, that is, 5.6%, 20.0%, and 45.5% in the vessel diameter groups ≥2.0, 1.5-2.0, and ≤1.5 mm, respectively. The SAH incidence was significantly higher in narrower vessel groups. The occluded vessel diameter and the contact method with clots predicted clinical outcomes. CONCLUSIONS: Matching strategy-based thrombectomy yields acceptable efficiency and safety results. In narrower vessels, it is optimal to engage matched aspiration catheters and clots without the assistance of conventional stent retrievers.

Enhancing clinical safety in bioengineered-root regeneration: The use of animal component-free medium.

Background: Most studies used animal serum-containing medium for bioengineered-root regeneration, but ethical and safety issues raised by animal serum are a potentially significant risk for clinical use. Thus, this study aimed to find a safer method for bioengineered-root regeneration. Methods: The biological properties of human dental pulp stem cells (hDPSCs) cultured in animal component-free (ACF) medium or serum-containing medium (5%, 10% serum-containing medium, SCM) were compared in vitro. hDPSCs were cultured in a three-dimensional (3D) environment with human-treated dentin matrix (hTDM). The capacity for odontogenesis was compared using quantitative real-time PCR (qPCR) and Western blot. Subsequently, the hDPSCs/hTDM complexes were transplanted into nude mice subcutaneously. Histological staining was then used to verify the regeneration effect in vivo. Results: ACF medium promoted the migration of hDPSCs, but slightly inhibited the proliferation of hDPSCs in the first three days of culture compared to SCM. However, it had no significant effect on cell aging and apoptosis. After 7 days of 3D culture in ACF medium with hTDM, qPCR showed that DMP1, DSPP, OCN, RUNX2, and ß-tubulin III were highly expressed in hDPSCs. In addition, 3D cultured hDPSCs/hTDM complexes in ACF medium regenerated dentin, pulp, and periodontal ligament-like tissues similar to SCM groups in vivo. Conclusion: ACF medium was proved to be an alternative medium for bioengineered-root regeneration. The strategy of using ACF medium to regenerate bioengineered-root can improve clinical safety for tooth tissue engineering.

GABAA receptors and neuroligin 2 synergize to promote synaptic adhesion and inhibitory synaptogenesis.

GABAA receptors (γ-aminobutyric acid-gated receptors type A; GABAARs), the major structural and functional postsynaptic components of inhibitory synapses in the mammalian brain, belong to a family of GABA-gated Cl-/HCO3 - ion channels. They are assembled as heteropentamers from a family of subunits including: α (1-6), ß(1-3), γ(1-3), δ, ε, π, θ and ρ(1-3). GABAARs together with the postsynaptic adhesion protein Neuroligin 2 (NL2) and many other pre- and post-synaptic proteins guide the initiation and functional maturation of inhibitory GABAergic synapses. This study examined how GABAARs and NL2 interact with each other to initiate the formation of synapses. Two functionally distinct GABAAR subtypes, the synaptic type α2ß2γ2-GABAARs versus extrasynaptic type α4ß3δ-GABAARs were expressed in HEK293 cells alone or together with NL2 and co-cultured with striatal GABAergic medium spiny neurons to enable innervation of HEK293 cells by GABAergic axons. When expressed alone, only the synaptic α2ß2γ2-GABAARs induced innervation of HEK293 cells. However, when GABAARs were co-expressed with NL2, the effect on synapse formation exceeded the individual effects of these proteins indicating a synergistic interaction, with α2ß2γ2-GABAAR/NL2 showing a significantly greater synaptogenic activity than α4ß3δ-GABAAR/NL2 or NL2 alone. To investigate the molecular basis of this interaction, different combinations of GABAAR subunits and NL2 were co-expressed, and the degree of innervation and synaptic activity assessed, revealing a key role of the γ2 subunit. In biochemical assays, the interaction between NL2 and α2ß2γ2-GABAAR was established and mapped to the large intracellular domain of the γ2 subunit.

Engineering d-p Orbital Hybridization in Mo-O Species of Medium-Entropy Metal Oxides as Highly Active and Stable Electrocatalysts toward Ampere-Level Water/Seawater Splitting.

Optimizing the electronic structure of electrocatalysts is of particular importance to enhance the intrinsic activity of active sites in water/seawater. Herein, a series of medium-entropy metal oxides of X(NiMo)O2/NF (X = Mn, Fe, Co, Cu and Zn) is designed via a rapid carbothermal shocking method. Among them, the optimized medium-entropy metal oxide (FeNiMo)O2/NF delivered remarkable HER performance, where the overpotentials as low as 110 and 141 mV are realized at 1000 mA cm-2 (@60 °C) in water and seawater. Meanwhile, medium-entropy metal oxide (FeNiMo)O2/NF only required overpotentials of as low as 330 and 380 mV to drive 1000 mA cm-2 for OER in water and seawater (@60 °C). Theoretical calculations showed that the multiple-metal synergistic effect in medium-entropy metal oxides can effectively enhance the d-p orbital hybridization of Mo─O bond, reduce the energy barrier of H* adsorbed at the Mo sites. Meanwhile, Fe sites in medium-entropy metal oxide can act as the real OER active center, resulting in a good bifunctional activity. In all, this work provides a feasible strategy for the development of highly active and stable medium-entropy metal oxide electrocatalysts for ampere-level water/seawater splitting.

Harmonization of experimental procedures to assess mitochondrial respiration in human permeabilized skeletal muscle fibers.

AIM: High-resolution respirometry in human permeabilized muscle fibers is extensively used for analysis of mitochondrial adaptions to nutrition and exercise interventions, and is linked to athletic performance. However, the lack of standardization of experimental conditions limits quantitative inter- and intra-laboratory comparisons. METHODS: In our study, an international team of investigators measured mitochondrial respiration of permeabilized muscle fibers obtained from three biopsies (vastus lateralis) from the same healthy volunteer to avoid inter-individual variability. High-resolution respirometry assays were performed together at the same laboratory to assess whether the heterogenity in published results are due to the effects of respiration media (MiR05 versus Z) with or without the myosin inhibitor blebbistatin at low- and high-oxygen regimes. RESULTS: Our findings reveal significant differences between respiration media for OXPHOS and ET capacities supported by NADH&succinate-linked substrates at different oxygen concentrations. Respiratory capacities were approximately 1.5-fold higher in MiR05 at high-oxygen regimes compared to medium Z near air saturation. The presence or absence of blebbistatin in human permeabilized muscle fiber preparations was without effect on oxygen flux. CONCLUSION: Our study constitutes a basis to harmonize and establish optimum experimental conditions for respirometric studies of permeabilized human skeletal muscle fibers to improve reproducibility.

Effect of electrical muscle stimulation on the improvement of deltoid muscle atrophy in a rat shoulder immobilization model.

Immobilization following trauma or surgery induces skeletal muscle atrophy, and improvement in the muscle atrophy is critical for successful clinical outcomes. The purpose of this study is to evaluate the effect of electrical muscle stimulation (EMS) on muscle atrophy. The study design is a controlled laboratory study. Eighty rats (56 to establish the deltoid muscle atrophy [DMA] model and 24 to evaluate the effect of EMS on the model) were used. DMA was induced by completely immobilizing the right shoulder of each rat by placing sutures between the scapula and humeral shaft, with the left shoulder as a control. After establishing the DMA model, rats were randomly assigned into three groups: low-frequency EMS (L-EMS, 10 Hz frequency), medium-frequency EMS (M-EMS, 50 Hz frequency), and control (eight rats per group). After 3 weeks, the deltoid muscles of each rat were harvested, alterations in gene expression and muscle cell size were evaluated, and immunohistochemical analysis was performed. DMA was most prominent 3 weeks after shoulder immobilization. Murf1 and Atrogin were significantly induced at the initial phase and gradually decreased at approximately 3 weeks; however, MyoD expressed an inverse relationship with Murf1 and Atrogin. IL6 expression was prominent at 1 week. The time point for the EMS effect evaluation was selected at 3 weeks, when the DMA was the most prominent with a change in relevant gene expression. The M-EMS group cell size was significantly larger than that of L-EMS and control group in both the immobilized and intact shoulders (all p < 0.05), without significant differences between the L-EMS and control groups. The M-EMS group showed significantly lower mRNA expressions of Murf1 and Atrogin and higher expressions of MyoD and Col1A1 than that of the control group (all p < 0.05). In immunohistochemical analysis, similar results were observed with lower Atrogin staining and higher MyoD and Col1A1 staining in the M-EMS group. DMA model was established by complete shoulder immobilization, with the most prominent muscle atrophy observed at 3 weeks. M-EMS improved DMA with changes in the expression of relevant genes. M-EMS might be a solution for strengthening atrophied skeletal muscles and facilitating rehabilitation after trauma or surgery.

Discovery of Cell Number-Interstitial Fluid Volume (CIF) Ratio Reveals Secretory Autophagy Pathway to Supply eHsp90α for Wound Healing.

Cell secretion repairs tissue damage and restores homeostasis throughout adult life. The extracellular heat shock protein-90alpha (eHsp90α) has been reported as an exosome cargo and a potential driver of wound healing. However, neither the mechanism of secretion nor the genetic evidence for eHsp90α in wound healing has been substantiated. Herein, we show that tissue injury causes massive deposition of eHsp90α in tissues and secretion of eHsp90α by cells. Sequential centrifugations of conditioned medium from relevant cell lines revealed the relative distributions of eHsp90α in microvesicle, exosome and trypsin-sensitive supernatant fractions to be approximately <2%, <4% and >95%, respectively. Establishing the cell-number-to-interstitial-fluid-volume (CIF) ratio for the microenvironment of human tissues as 1 × 109 cells: 1 mL interstitial fluid enabled us to predict the corresponding tissue concentrations of eHsp90α in these fractions as 3.74 µg/mL, 5.61 µg/mL and 178 µg/mL. Remarkably, the 178 µg/mL eHsp90α matches the previously reported 100-300 µg/mL of recombinant eHsp90α whose topical application promotes maximum wound healing in animal models. More importantly, we demonstrate that two parallel secretory autophagy-regulating gene families, the autophagy-regulating (AR) genes and the Golgi reassembly-stacking protein (GRASP) genes work together to mediate the secretion of the physiological concentration of eHsp90α to promote wound healing. Thus, utilization of the CIF ratio-based extrapolation method may enable investigators to rapidly predict biomarker targets from cell-conditioned-medium data.

Improving medium-range streamflow forecasts over South Korea with a dual-encoder transformer model.

Accurate and reliable hydrological forecasts play a pivotal role in ensuring water security, facilitating flood preparedness, and supporting agriculture activities. This study investigates the potential of hydrological forecasting in South Korea, focusing on medium-range lead times ranging from 1 to 10 days. The methodology involves leveraging a Transformer neural network, a model entirely based on attention mechanisms. Specifically, our study introduces the Dualformer, a dual-encoder-based transformer model capable of accommodating two distinct datasets: historical and forecast meteorological data. The performance of this proposed model, along with its variants designed to test specific structural aspects, is evaluated in predicting daily streamflow across 473 grid cells covering extensive regions within the study area. Furthermore, the proposed model is assessed against the performance of a recently developed approach aiming for the same objective. These models are trained using historical meteorological variables and geographic characteristics, alongside the Global Ensemble Forecast System, version 12 (GEFSv12) reforecasts, in addition to historical runoff. The results indicate that our proposed model performs competitively, especially for relatively short lead times while effectively managing information from two distinct data sources. For instance, the mean Nash-Sutcliffe efficiency for 473 grids is 0.664 for the first one-day lead when using the Dualformer, whereas the benchmark model achieves a score of 0.535. Additionally, we observe an additional enhancement in Dualformer's performance when utilizing a larger dataset. Finally, we conclude this paper with a discussion regarding potential improvements to the forecast model through the incorporation of additional input and modeling structures.

Expansion of human allogeneic liver-derived progenitor cells for liver regenerative therapy in serum-free culture conditions.

Human allogeneic liver-derived progenitor cells (HALPCs) display advanced ability to differentiate into hepatocyte-like cells and exhibit potent immunomodulatory, anti-inflammatory, and anti-fibrotic properties. HALPCs have been successfully manufactured under good manufacturing practice (GMP) and are currently in clinical development. A previous phase 2a trial demonstrated the safety of peripheral intravenous infusions of HALPCs and preliminary evidence of the cells' properties to restore liver function in patients with acute-on-chronic liver failure (ACLF), thus potentially improving their survival. A phase 2b trial is currently ongoing across multiple centers (NCT04229901) to obtain proof-of-concept on efficacy and additional safety. HALPCs are currently manufactured using fetal bovine serum (FBS), which can reveal qualitative and quantitative variations between batches. The use of serum-free medium (SFM) represents an alternative means to overcome this variability while also complying fully with regulations. The aim of this study was to compare current FBS-containing culture conditions with two industry-available GMP-compliant SFMs: StemMACS (Miltenyi Biotec, Bergisch Gladbach, Germany) and PRIME-XV (FUJIFILM Irvine Scientific, Santa Ana, California, USA). The proliferation of HALPCs was significantly stimulated by both SFMs, which shortened both their emergence period and population doubling time. This effect was correlated with a significant improvement in their genetic stability as analyzed by conventional karyotyping. The expression profile (identity and purity) and functionality of HALPCs cultured in SFM were maintained, as demonstrated by flow cytometry and enzyme-linked immunoassay (ELISA), respectively. Their potency, evaluated via prostaglandin E2 (PGE2) secretion, showed a similar effect on CD4+ T-cell proliferation in FBS and SFM conditions. Furthermore, a greater proportion of HALPCs cultured in SFM showed enhanced expression of tissue factor (CD142) compared with the FBS condition. Altogether, SFM conditions enabled consistent HALPC quality to be achieved without altering their expression and functional profiles.

A single-nucleus transcriptomic atlas of medium spiny neurons in the rat nucleus accumbens.

Neural processing of rewarding stimuli involves several distinct regions, including the nucleus accumbens (NAc). The majority of NAc neurons are GABAergic projection neurons known as medium spiny neurons (MSNs). MSNs are broadly defined by dopamine receptor expression, but evidence suggests that a wider array of subtypes exist. To study MSN heterogeneity, we analyzed single-nucleus RNA sequencing data from the largest available rat NAc dataset. Analysis of 48,040 NAc MSN nuclei identified major populations belonging to the striosome and matrix compartments. Integration with mouse and human data indicated consistency across species and disease-relevance scoring using genome-wide association study results revealed potentially differential roles for MSN populations in substance use disorders. Additional high-resolution clustering identified 34 transcriptomically distinct subtypes of MSNs definable by a limited number of marker genes. Together, these data demonstrate the diversity of MSNs in the NAc and provide a basis for more targeted genetic manipulation of specific populations.

Data analysis of thermal performance and irreversibility of convective flow in porous-wavy channel having triangular obstacle under magnetic field effect.

Mixed convective nanofluid flow has substantial importance in improvement of thermal performance, and thermal engineering to meet the global energy crisis. In this study, mixed convective nanofluid flow in a porous-wavy channel with an inner heated triangular obstacle under magnetic field effect is numerically examined. Nanofluid within the channel is heated and cooled from its bottom and top wavy-surfaces. A heated triangular cylinder is located at the centerline of the wavy-channel. Finite element method is utilized to solve the non-dimensional governing equations. The code is validated comparing present results with published numerical and experimental results. The response surface method is also implemented to analyze the obtained results and its sensitivity. The numerical results indicate that strength of flow velocity is accelerated with rising Reynolds number, Darcy numbers and inlet-outlet ports length but declined for Hartmann number and volume fraction. Heat transferring rate and heat transfer irreversibility are substantially increased for higher values of Reynolds number, inlet-outlet ports length, Darcy number and nanoparticle volume fraction but a reverse trend is occurred for magnetic field effect. The thermal performance is found significantly improved with simultaneous increment in Re, ϕ, Da and decrement in Ha. Positive sensitivity is achieved for input factors Re, ϕ, Da in computing N u a v while negative sensitivity to Ha. Heat transfer rate is found more sensitive to the impact of Re and ϕ compared to Da and Ha. 45.59 % more heat transmission potentiality is developed for using Al2O3-H2O nanofluid (vol.5 %) instead of using base fluid water. Heat transfer enhancement rate is decreased by 36.22 % due to impact of magnetic field strength. In addition, 84.12 % more heat transferring rate is recorded in presence of triangular obstacle. Moreover, irreversibility components are influenced significantly for the presence of heated triangular obstacle. Bejan number is also found declined for increasing physical parameters. The findings of this investigation may offer a guideline for finding experimental results to design high-performance convective heat exchangers.

Expanded Hemodialysis Enhancement in Middle Molecule Clearance for Patients With Low Blood Flow Rates of Tunneled Dialysis Catheters.

INTRODUCTION: Expanded hemodialysis (HDx), being based on medium cut-off (MCO) membranes, improves the removal of medium molecule uremic toxins. HDx efficacy has been proven with blood flow rates (Qb) of 350-400 ml/min, while low Qb have only been assessed in single sessions. We evaluated the effectiveness of HDx in patients with tunneled central venous catheters (CVCs) and low Qb over six months, comparing it with high-flux hemodialysis (HF-HD). METHODS: The study included 10 patients with a mean age of 79±12 years and mean Qb of 237 ± 12 ml/min. Reduction ratios (RRs) and predialysis serum levels were measured for ß2-microglobulin (B2M), free κ and λ light chains (FLC), prolactin (PRL), interleukin-6 (IL-6), albumin, and urea after HF-HD and at one, three, and six months of HDx. Erythropoiesis-stimulating agent (ESA) resistance index (ERI) was also evaluated. RESULTS: B2M, κ-FLC, λ-FLC, and PRL RRs were significantly higher with HDx. IL-6, albumin, and urea RRs did not show a statistical difference between the two treatments. Predialysis B2M concentrations were significantly lower after three and six months of HDx, matching up to increased B2M clearance (spKt/V). A decrease in albumin concentrations was observed, with median levels significantly reduced at months seven and eight (35.3 and 35.5 g/L, respectively) but recovering afterwards. ERI was significantly lower during HDx, reaching a 30% reduction at month six. CONCLUSIONS: HDx was feasible, safe, and superior to HF-HD in patients with low Qb rates of tunneled dialysis catheters. The present data expand options for HDx prescription, with particular regard for patients who cannot achieve high convective volumes due to inadequate vascular access.