Platelet-derived TGF-ß1 induces functional reprogramming of myeloid-derived suppressor cells in immune thrombocytopenia.

ABSTRACT: Platelet α-granules are rich in transforming growth factor ß1 (TGF-ß1), which is associated with myeloid-derived suppressor cell (MDSC) biology. Responders to thrombopoietin receptor agonists (TPO-RAs) revealed a parallel increase in the number of both platelets and MDSCs. Here, anti-CD61 immune-sensitized splenocytes were transferred into severe combined immunodeficient mice to establish an active murine model of immune thrombocytopenia (ITP). Subsequently, we demonstrated that TPO-RAs augmented the inhibitory activities of MDSCs by arresting plasma cells differentiation, reducing Fas ligand expression on cytotoxic T cells, and rebalancing T-cell subsets. Mechanistically, transcriptome analysis confirmed the participation of TGF-ß/Smad pathways in TPO-RA-corrected MDSCs, which was offset by Smad2/3 knockdown. In platelet TGF-ß1-deficient mice, TPO-RA-induced amplification and enhanced suppressive capacity of MDSCs was waived. Furthermore, our retrospective data revealed that patients with ITP achieving complete platelet response showed superior long-term outcomes compared with those who only reach partial response. In conclusion, we demonstrate that platelet TGF-ß1 induces the expansion and functional reprogramming of MDSCs via the TGF-ß/Smad pathway. These data indicate that platelet recovery not only serves as an end point of treatment response but also paves the way for immune homeostasis in immune-mediated thrombocytopenia.

Modelling of liquid film migration in Al-Cu alloys.

Microstructural evolution in the presence of liquid film migration (LFM) is simulated for Al-Cu alloys using a cellular automaton (CA) model. Simulations are performed for the microstructural evolution and concentration distribution in an Al-4 wt.%Cu alloy with initially equiaxed grain structures holding in a temperature gradient. A slight deviation from local equilibrium, estimated from experimental data, is considered to be the driving force for LFM. The direction of LFM is triggered by concentration fluctuations setting a concentration gradient as a further driving force. The simulation successfully reproduces the experimentally observed microstructures generated by LFM accompanied by a particle free zone behind the liquid film. The solid concentration in the particle free zone is found to be the equilibrium solid concentration. The simulated concentration profile across the migrating liquid film agrees well with experimental measurements. The simulated grain structure becomes coarser and highly elongated after holding in the temperature gradient. The results reveal that the increase in transversal grain width is mainly controlled by LFM, while the grain elongation in longitudinal direction is attributed to both LFM and temperature gradient zone melting. The solid concentration decreases from the initial (supersaturated) composition to the local equilibrium solid concentration corresponding to the local temperature. This article is part of the theme issue 'Transport phenomena in complex systems (part 2)'.

Modeling of free dendritic growth in a gravity environment by lattice Boltzmann method.

A two-dimensional model is developed to simulate dendrite growth and movement in a gravity environment. The model combines the features of cellular automaton and lattice Boltzmann methods. Two sets of distribution functions are adopted to calculate the melt flow and solute transport simultaneously. The fluid force acting on the dendrite is calculated by extending the basic flow simulation at the solid-liquid interface. Incorporating the force interaction between melt flow and solidified dendrite into the algorithm for dendritic growth, the movement of a growing dendrite in the flowing melt can be simulated. After model validation, the coupled model has been applied to simulate the evolution and motion of an individual nucleus that grows into a dendrite in the presence of gravitational force. It is found that the dendrite growth is strongly influenced by the fluid flow, producing an asymmetrical morphology that the dendrite grows faster in the upstream direction, whereas largely slower in the downstream direction. The growth process of dendritic side-branches is modeled in a high settling velocity without any artificial noise introduced. The melt flow triggered by the dendrite motion enhances the growth of the dendrite in the downward direction, which in turn influences the subsequent dendritic translation.

Cellular automaton modeling of peritectic transformation⋆.

A two-dimensional multiphase cellular automaton (CA) model is proposed for the prediction of growth kinetics and microstructural evolution during peritectic transformation of Fe-C alloys. The proposed model is validated by comparing the simulation results with the experimental measurements and analytical predictions for the growth kinetics of the [Formula: see text] -phase and the concentration distributions. The simulated time evolution of the [Formula: see text] -phase thickness and the concentration distribution in the [Formula: see text] -phase agree well with the experimental data, demonstrating the quantitative capabilities of the proposed model. The influences of the holding temperature and [Formula: see text] -phase thickness on the [Formula: see text] -phase growth behavior are analyzed based on the simulation results. The [Formula: see text] -phase growth velocity is found to decrease with increasing the [Formula: see text] -phase thickness and holding temperature. Simulations are also performed for the microstructural evolution during isothermal peritectic transformation of Fe-C alloys with the primary [Formula: see text] -phase being an equiaxed dendrite under different holding temperatures. It is found that the driving force for [Formula: see text] -phase growth increases with decreasing temperature.

Competitive dendrite growth during directional solidification of a transparent alloy: Modeling and experiment.

A two-dimensional (2-D) cellular automaton-finite difference method (CA-FDM) model and in situ observation experiments of directional solidification using a transparent alloy of SCN-2wt.% ACE are employed to investigate various microstructural evolution of columnar dendrites during directional solidification. In the present model, the growth of columnar dendrites is simulated using a CA technique. The solute diffusion is solved using the FDM. The model is capable of visualizing the interaction between the formation of dendrite arrays with identical or different growth orientations, and the evolving solute concentration field. Several dendritic competitive growth modes between two converging and diverging dendrite arrays are reproduced. The simulation results agree well with the experimental observations. The simulations are also performed to study the effects of temperature gradient and cooling rate on the growth morphology of diverging dendrites. It is found that with the increase of temperature gradient and cooling rate, the tertiary branches produced from the well-developed side branches of the unfavorably oriented grain at the divergent grain boundaries are more likely to become the new primary dendrite arms.

Modeling of dendrite arm fragmentation and dendrite arm coarsening⋆.

A two-dimensional quantitative cellular automaton (CA) model is employed to simulate dendrite arm fragmentation and dendrite arm coarsening in mushy zones. The phenomenon of dendrite arm fragmentation of an Al-Cu alloy during heating is well represented by the CA simulation, and it is analyzed in detail by comparing the local actual concentration and local equilibrium concentration. The CA simulations for the dendritic microstructures of SCN-ACE alloys during isothermal holding in a mushy zone reproduce the typical dendrite coarsening features as observed in experiments. The effects of holding temperature and alloy composition on the microstructures and dendrite coarsening kinetics are investigated. It is found that the melting of small dendrite arms and interdendritic groove advancement are the two main mechanisms in dendrite coarsening. The mechanism of coalescence by joining arm tips is more likely to take place at a lower temperature or for a lower alloy composition, while the dendrite arm fragmentation mechanism tends to occur at a higher temperature. The coarsening rate constant is found to decrease with increasing holding temperature and alloy composition.

Simultaneous melting and solidification of a columnar dendritic microstructure in a temperature gradient: Numerical modeling and experiments⋆.

The microstructural evolution of a SCN-ACE alloy in a temperature gradient is studied by cellular automaton (CA) modeling and in situ experiments. The initially columnar dendrites gradually evolve to a completely solid region with a planar solid/liquid interface. The CA simulations and in situ observations present the migration of secondary dendrite arms and liquid pockets due to temperature gradient zone melting (TGZM), and the movement of the interface between a mushy zone and a fully liquid zone. The CA simulations show that the interface movement toward the lower temperature region is caused by the increasing concentration of the fully liquid region. Through updating the concentration in the fully liquid zone to the initial concentration in the CA simulation for mimicking the efficient stirring in liquid, the movement of the interface between the mushy zone and the fully liquid zone is hindered. The simulated liquid fractions and mean concentrations throughout the mushy zone decrease with time, which agree well with the analytical predictions. The simulated concentrations in the resolidified mushy zone are not higher than the temperature-dependent solidus concentrations, implying that no supersaturation remains after the mushy zone fully solidifies.

Lattice Boltzmann modeling of droplet condensation on superhydrophobic nanoarrays.

Droplet nucleation and growth on superhydrophobic nanoarrays is simulated by employing a multiphase, multicomponent lattice Boltzmann (LB) model. Three typical preferential nucleation modes of condensate droplets are observed through LB simulations with various geometrical parameters of nanoarrays, which are found to influence the wetting properties of nanostructured surfaces significantly. The droplets nucleated at the top of posts (top nucleation) or in the upside interpost space of nanoarrays (side nucleation) will generate a nonwetting Cassie state, while the ones nucleated at the bottom corners between the posts of nanoarrays (bottom nucleation) produce a wetting Wenzel state. The simulated time evolutions of droplet pressures at different locations are analyzed, which offers insight into the underlying physics governing the motion of droplets growing from different nucleation modes. It is demonstrated that the nanostructures with taller posts and a high ratio of post height to interpost space (H/S) are beneficial to produce the top- and side-nucleation modes. The simulated wetting states of condensate droplets on the nanostructures, having various geometrical configurations, compare reasonably well with experimental observations. The established relationship between the geometrical parameters of nanoarrays and the preferential nucleation modes of condensate droplets provides guidance for the design of nanoarrays with desirable anticondensation superhydrophobic properties.

Dietary factors and Alzheimer's disease risk: a Mendelian randomization study.

BACKGROUND: Prior observational research has investigated the association between dietary patterns and Alzheimer's disease (AD) risk. Nevertheless, due to constraints in past observational studies, establishing a causal link between dietary habits and AD remains challenging. METHODS: Methodology involved the utilization of extensive cohorts sourced from publicly accessible genome-wide association study (GWAS) datasets of European descent for conducting Mendelian randomization (MR) analyses. The principal analytical technique utilized was the inverse-variance weighted (IVW) method. RESULTS: The MR analysis conducted in this study found no statistically significant causal association between 20 dietary habits and the risk of AD (All p > 0.05). These results were consistent across various MR methods employed, including MR-Egger, weighted median, simple mode, and weighted mode approaches. Moreover, there was no evidence of horizontal pleiotropy detected (All p > 0.05). CONCLUSION: In this MR analysis, our finding did not provide evidence to support the causal genetic relationships between dietary habits and AD risk.

A Case of Squamous Cell Carcinoma Arising in Disseminated Superficial Porokeratosis.

Porokeratosis (PK), characterized by keratotic lesions with an atrophic center and a prominent peripheral ridge, with a typical histological hallmark, namely, the cornoid lamella, has two forms: disseminated and localized. While PK often converts into squamous cell carcinoma (SCC), conversion from disseminated superficial porokeratosis (DSP) alone is rarely reported except for one case in which DSP and LP coexisted and converted to SCC. Here, we report the case of a patient with SCC converted from DSP alone, presenting with coin-sized macules on the bottom right of his waist that developed into an ulcer at the center. The patient underwent radiation therapy, which effectively treated the SCC but did not resolve the PK. This article highlights regular follow-up and undergo comprehensive diagnosis, both of which are beneficial to enable early detection and management of DSP that has converted to into SCC; in addition, standardized medical treatment may help improve the treatment therapeutic effect of in similar diseases.

Association between allergic diseases and both psoriasis and psoriatic arthritis: a bidirectional 2-sample Mendelian randomization study.

Background An increasing body of observational studies has indicated a potential link between allergic diseases, namely atopic dermatitis (AD), allergic rhinitis (AR), allergic asthma (AA), and psoriasis (PSO) as well as psoriatic arthritis (PSA). However, the presence and causal direction of this association remain uncertain. Methods We conducted two-sample Mendelian randomization (TSMR) analyses utilizing summary statistics derived from genome-wide association studies (GWAS) consortia. The summary statistics were obtained from a substantial participant cohort, consisting of 116,000 individuals (21,000 AD cases and 95,000 controls), 462,933 individuals (26,107 AR cases and 436,826 controls), and 140,308 individuals (4859 AA cases and 135,449 controls). The summary statistics for PSO (9267 cases and 360,471 controls) and PSA (3186 cases and 240,862 controls) were sourced from the FinnGen database. The primary analytical approach employed inverse variance weighting (IVW) as the main method within TSMR. We validated our findings through a series of sensitivity analyses. Furthermore, we performed reverse TSMR analyses to evaluate the potential presence of reverse causality. Results Our investigation revealed a potential protective effect of AD against both PSO (OR = 0.922, 95% CI = 0.863-0.984, p = 0.015)and PSA(OR = 0.915, 95% CI = 0.843-0.993, p = 0.033). Moreover, employing inverse MR analysis, we obtained compelling evidence supporting the protective role of PSO in preventing AD (OR = 0.891, 95% CI = 0.829-0.958, p = 0.002), as well as AR (OR = 0.998, 95% CI = 0.996-0.999, p = 0.008), these associations remained statistically significant even after Bonferroni correction was applied to account for multiple comparisons. Furthermore, our findings did not reveal any substantial causal relationship between AA and either PSO or PSA. Conclusion Our study provides compelling evidence that PSO significantly confers protection against both AD and AR, while AD is likely to act as a protective factor for both PSO and PSA. Despite previous studies suggesting an association between allergic diseases and the incidence of PSO and PSA, our findings do not support this claim. To obtain more accurate and reliable conclusions regarding the causal mechanisms involved, larger sample sizes in randomized controlled trials or MR studies are warranted.

Revealing the Impact of Gut Microbiota on Acne Through Mendelian Randomization Analysis.

Background: The association between acne and gut microbiota has garnered considerable attention; nevertheless, given the substantial diversity within gut microbiota, the precise cause-and-effect relationship linking specific microbial species to acne remains elusive. To address this gap in knowledge, our study utilized Mendelian randomization analysis to elucidate a potential causal link between gut microbiota composition and acne development while also investigating underlying mechanisms involving microbial factors associated with metabolic disorders. Materials and Methods: The independent single nucleotide polymorphisms (SNPs) closely associated with 196 gut microbiota samples (N=18340) were selected as variable tools. The relationship between gut microbiota and acne (N=212438) was analyzed using the Twosample package in R4.3.1, employing various methods including inverse variance weighting (IVW), weighted median, MR-Egger, Simple-mode, and Weighted-mode. To ensure the stability of the estimates, a series of sensitivity analyses were conducted, such as Cochran's Q-test, MR-Egger intercept analysis, leave-one-out analysis, and funnel plots. Additionally, the impact of each instrumental variable was calculated. Results: In the Mendelian randomization analysis, we identified twelve microbial taxa potentially associated with acne: family.Bacteroidaceae, family.Clostridiaceae1, genus.Allisonella, genus.Bacteroides, genus.Butyricimonas, genus.Clostridiumsensustricto1, and genus.Coprococcus3. These seven bacterial groups were found to be potential risk factors for acne. Conversely, family.Lactobacillaceae and genus.Ruminococcustorquesgroup along with genus.CandidatusSoleaferrea, genus.Fusicatenibacter, family.Lactobacillaceae, and genus.Lactobacillus exhibited a protective effect against acne. Furthermore, our investigation revealed that some of these microbial taxa have been implicated in metabolic diseases through previous studies. Importantly though, no causal relationship was observed in the reverse Mendelian randomization analysis.

Research progress on the role of macrophages in acne and regulation by natural plant products.

Acne vulgaris is one of the most common skin diseases. The current understanding of acne primarily revolves around inflammatory responses, sebum metabolism disorders, aberrant hormone and receptor expression, colonization by Cutibacterium acnes, and abnormal keratinization of follicular sebaceous glands. Although the precise mechanism of action remains incompletely understood, it is plausible that macrophages exert an influence on these pathological features. Macrophages, as a constituent of the human innate immune system, typically manifest distinct phenotypes across various diseases. It has been observed that the polarization of macrophages toward the M1 phenotype plays a pivotal role in the pathogenesis of acne. In recent years, extensive research on acne has revealed an increasing number of natural remedies exhibiting therapeutic efficacy through the modulation of macrophage polarization. This review investigates the role of cutaneous macrophages, elucidates their potential significance in the pathogenesis of acne, a prevalent chronic inflammatory skin disorder, and explores the therapeutic mechanisms of natural plant products targeting macrophages. Despite these insights, the precise role of macrophages in the pathogenesis of acne remains poorly elucidated. Subsequent investigations in this domain will further illuminate the pathogenesis of acne and potentially offer guidance for identifying novel therapeutic targets for this condition.

Simultaneous detection of norepinephrine and 5-hydroxytryptophan using poly-alizarin/multi-walled carbon nanotubes-graphene modified carbon fiber microelectrode array sensor.

Multi-walled carbon nanotubes, graphene and alizarin polymer composites coated carbon fiber microelectrode array sensor (p-AZ/MWCNT-GR/CFMEA) was constructed and used for the simultaneous detection of norepinephrine (NE) and 5-hydroxytryptophan (5-HT). The morphology and structural characteristics of sensor are characterized using scanning electron microscopy, energy dispersive spectroscopy and X-ray diffraction. Its electrochemical behavior has been studied with cyclic voltammetry and electrochemical impedance spectroscopy. The sensor exhibits excellent electrochemical activity for the oxidation of NE and 5-HT, two well separated oxidation peaks with the peak potential difference of 220 mV are observed on the cyclic voltammogram. NE and 5-HT both show two electrons and two protons electrochemical reaction on the p-AZ/MWCNT-GR/CFMEA. Under the optimized experiment conditions, the linear ranges of the sensor for NE and 5-HT are 0. 08- 8 µM and 0. 1-20 µM with detection limits of 4. 22 nM and 14. 2 nM (S/N = 3), respectively. In addition, the microsensor array show good reproducibility, stability and selectivity for the determination of NE and 5-HT. Finally, the p-AZ/MWCNT-GR/CFMEA is applied to the simultaneous detection of NE and 5-HT in human serum samples and macrophages.

Systemic immune-inflammation index is associated with cardiac complications following acute ischemic stroke: A retrospective single-center study.

BACKGROUND: Stroke-induced heart syndrome is a feared complication of ischemic stroke, that is commonly encountered and has a strong association with unfavorable prognosis. More research is needed to explore underlying mechanisms and inform clinical decision making. This study aims to explore the relationship between the early systemic immune-inflammation (SII) index and the cardiac complications after acute ischemic stroke. METHODS: Consecutive patients with acute ischemic stroke were prospectively collected from January 2020 to August 2022 and retrospectively analyzed. We included subjects who presented within 24 hours after symptom onset and were free of detectable infections or cancer on admission. SII index [(neutrophils × platelets/ lymphocytes)/1000] was calculated from laboratory data at admission. RESULTS: A total of 121 patients were included in our study, of which 24 (19.8 %) developed cardiac complications within 14 days following acute ischemic stroke. The SII level was found higher in patients with stroke-heart syndrome (p<.001), which was an independent predictor of stroke-heart syndrome (adjusted odds ratio 5.089, p=.002). CONCLUSION: New-onset cardiovascular complications diagnosed following a stroke are very common and are associated with early SII index.

Giant tumefactive perivascular spaces.

Perivascular spaces are parts of the glymphatic pathway in the brain, which are microscopic but visible on magnetic resonance imaging when enlarged. Here, we described a case of a 16-year-old boy who presented with chronic headaches. Magnetic resonance imaging revealed giant perivascular spaces in the right centrum semiovale. Furtherly, we summarized the literature on classical and rare presentations of massive perivascular spaces and raised awareness that more clinical significance of the giant tumefactive perivascular spaces remains to be elucidated.

Lipid Metabolism Reprogramming of Immune Cells in Acne: An Update.

Acne vulgaris is one of the most widespread skin conditions and the main reason for visiting a dermatologist. Inflammatory response and abnormal infiltrations of immune cells are the main pathogenesis of acne. The increased lipid is the prerequisite for the acne, and the perturbation of lipid composition and content is consistent with the severity of acne. Furthermore, the increased lipid production not only contributes to the occurrence and development of acne, but also sensitizes the function of immune cells. The lipid metabolic dysfunction aggravates the severity of local tissue and provides pro-inflammatory-cytokine cues, which indicates the crucial roles of lipid metabolism on immune cells. Recent advances have demonstrated the lipid metabolism reprogramming of various immune cells in acne lesion. The abnormal lipid accumulation, lipolysis, and fatty acid oxidation lead to the activation and differentiation of immune cells, which promotes the pro-inflammatory cytokines production. Thus, this review discusses the emerging role of lipid metabolism reprogramming of immune cells in the progress of acne and aims to constitute food for others' projects involved in acne research.

Case report: Complete atrio-ventricular block successfully reversed in newly diagnosed primary cardiac B-cell lymphoma.

Primary cardiac tumors are extremely uncommon and primary cardiac lymphoma (PCL) is an even rarer subset. A definite diagnosis can be delayed, which increases the likelihood of a poor prognosis. We report a case involving a 64-year-old male who presented with dyspnea, palpitation, and third-degree atrioventricular block (AVB) secondary to primary cardiac B-cell lymphoma that was diagnosed via endomyocardial biopsy (EMB) and multimodality imaging. Chemotherapy was initiated using rituximab, cyclophosphamide, vindesine, and prednisone (R-COP) followed by implantation of an artificial capsule pacemaker. Third-degree AVB vanished, and the subsequent cycle of treatment was adjusted as R-CDOP (rituximab, cyclophosphamide, doxorubicin liposome, vindesine, and prednisone), with aspirin and rosavastatin to prevent ischemic events. So far, the patient had a good clinical course and normal electrocardiogram. This case underscores the importance of EMB in the diagnosis of heart neoplasms. It is worth noting that anthracycline is not contraindicated in PCL.

Acne Comorbidities.

Acne vulgaris is a multifactorial chronic inflammatory disorder of the pilosebaceous unit, and it represents the most common skin disease affecting about 85% of adolescents in Western populations. The prevalence of acne vulgaris in developed countries is higher than that in developing countries.Emerging data has shown some systemic diseases closely associated with acne, including obesity, diabetes mellitus, cardiovascular diseases, metabolic syndrome (Mets), and so on.This review summarizes acne-associated diseases that have been reported in studies, and analyzes the possible co-pathogenesis of these diseases and acne.

Folliculitis Decalvans and Lichen Planopilaris Phenotypic Spectrum: A Case Report.

The folliculitis decalvans (FD) and lichen planopilaris (LPP) phenotypic spectrum combines biphasic features of FD and LPP. It is characterized by successive or concomitant occurrence of pustules, crusts, follicular tufts, perifollicular erythema, perifollicular scales, and cicatricial alopecia and includes mixed histologic features of both FD and LPP. Here, we report the case of a 33-year-old female patient with a 30-year history of FD-LPP phenotypic spectrum lesions.