Exploration of a somatosensory interactive assessment tool for children with intellectual disabilities.

Based on the functional assessment concept and embodied assessment requirements, the present study aimed to design and develop an assessment tool for children with intellectual disabilities with the help of somatosensory interactive (SI) technology. The sample in this study consisted of 73 children with intellectual disabilities and 70 children with typical development. Data were collected through three SI tasks, four traditional executive function tasks, and user experience interviews to analyse the effectiveness of the SI assessment tool. The results showed that the SI assessment tool had good scale validity, discriminant validity, and the ability to identify intellectual disabilities. Children preferred SI tasks and showed higher involvement and more positive emotions. The SI tool with three SI tasks is a more scientific, effective, and advanced tool for assessing children with intellectual disabilities.

Laboratory blood parameters and machine learning for the prognosis of esophageal squamous cell carcinoma.

Background: In contemporary study, the death of esophageal squamous cell carcinoma (ESCC) patients need precise and expedient prognostic methodologies. Objective: To develop and validate a prognostic model tailored to ESCC patients, leveraging the power of machine learning (ML) techniques and drawing insights from comprehensive datasets of laboratory-derived blood parameters. Methods: Three ML approaches, including Gradient Boosting Machine (GBM), Random Survival Forest (RSF), and the classical Cox method, were employed to develop models on a dataset of 2521 ESCC patients with 27 features. The models were evaluated by concordance index (C-index) and time receiver operating characteristics (Time ROC) curves. We used the optimal model to evaluate the correlation between features and prognosis and divide patients into low- and high-risk groups by risk stratification. Its performance was analyzed by Kaplan-Meier curve and the comparison with AJCC8 stage. We further evaluate the comprehensive effectiveness of the model in ESCC subgroup by risk score and KDE (kernel density estimation) plotting. Results: RSF's C-index (0.746) and AUC (three-year AUC 0.761, five-year AUC 0.771) had slight advantage over GBM and the classical Cox method. Subsequently, 14 features such as N stage, T stage, surgical margin, tumor length, age, Dissected LN number, MCH, Na, FIB, DBIL, CL, treatment, vascular invasion, and tumor grade were selected to build the model. Based on these, we found significant difference for survival rate between low-(3-year OS 81.8%, 5-year OS 69.8%) and high-risk (3-year OS 25.1%, 5-year OS 11.5%) patients in training set, which was also verified in test set (all P < 0.0001). Compared with the AJCC8th stage system, it showed a greater discriminative ability which is also in good agreement with its staging ability. Conclusion: We developed an ESCC prognostic model with good performance by clinical features and laboratory blood parameters.

Spurious High Platelet Count without PLT Flag(S) in a Patient with Severe Aplastic Anaemia.

BACKGROUND: Platelet (PLT) count is one of the most important parameters of automated hematology, as spurious PLT reports could affect medical judgement and bring significant risks. In most cases, spurious PLT will not be reported for review criteria, which will be triggered by abnormal PLT histograms and PLT flag(s). Here, we present a case of severe aplastic anemia after hematopoietic stem cell transplantation with spurious high platelet count with normal histogram and no PLT flag(s). METHODS: The electrical impedance channel (PLT-I) and the fluorescence channel (PLT-F) of Sysmex XN-series hematology analyzer was used to obtain PLT results. Then, the sample was retested by another hematology analyzer MINDRAY BC-7500 [NR] CRP, and incubation was performed to rule out cryoglobulin interference. Furthermore, a microscope was used to estimate the PLT count by the ratio of platelets to red blood cells and observe the morphology of cells. RESULTS: Both PLT-I and PLT-F test results were spuriously high, and microscopically assessed platelet counts were relatively reliable. The observed spiny cells and ghost cells caused by hemolysis may have contributed to the inaccuracy of instrumental counting in this case. CONCLUSIONS: For special hematologic patients, PLT-I with flags may not be sufficient for screening purposes and PLT-F is not always accurate. Multiple testing methods including manual microscopy are needed.

Characterization of merozoite-specific thrombospondin-related anonymous protein (MTRAP) in Plasmodium vivax and P. knowlesi parasites.

Plasmodium vivax, the most widespread human malaria parasite, and P. knowlesi, an emerging Plasmodium that infects humans, are the phylogenetically closest malarial species that infect humans, which may induce cross-species reactivity across most co-endemic areas in Southeast Asia. The thrombospondin-related anonymous protein (TRAP) family is indispensable for motility and host cell invasion in the growth and development of Plasmodium parasites. The merozoite-specific TRAP (MTRAP), expressed in blood-stage merozoites, is supposed to be essential for human erythrocyte invasion. We aimed to characterize MTRAPs in blood-stage P. vivax and P. knowlesi parasites and ascertain their cross-species immunoreactivity. Recombinant P. vivax and P. knowlesi MTRAPs of full-length ectodomains were expressed in a mammalian expression system. The MTRAP-specific immunoglobulin G, obtained from immune animals, was used in an immunofluorescence assay for subcellular localization and invasion inhibitory activity in blood-stage parasites was determined. The cross-species humoral immune responses were analyzed in the sera of patients with P. vivax or P. knowlesi infections. The MTRAPs of P. vivax (PvMTRAP) and P. knowlesi (PkMTRAP) were localized on the rhoptry body of merozoites in blood-stage parasites. Both anti-PvMTRAP and anti-PkMTRAP antibodies inhibited erythrocyte invasion of blood-stage P. knowlesi parasites. The humoral immune response to PvMTRAP showed high immunogenicity, longevity, and cross-species immunoreactivity with P. knowlesi. MTRAPs are promising candidates for development of vaccines and therapeutics against vivax and knowlesi malaria.

Combining High-Density Fat and Condensed Low-Density Fat Injections for Precise Facial Rejuvenation.

BACKGROUND: Facial aging involves ptosis, adipose atrophy, and skeletal resorption. Depletion of adipose tissue primarily affects the deep facial fat compartment, leading to facial depression or ptosis, accompanied by atrophy of the superficial compartment. Restoring volume in the deep fat compartment is crucial for facial rejuvenation, while enhancing its supportive properties is also important. The superficial fat compartment contains small-sized adipocytes, and autologous fat grafting is a popular approach. However, variability in fat retention, homogeneity, and processing methods can impact outcomes, necessitating careful selection of a suitable fat processing material for precise facial fat grafting. METHOD: A retrospective study was conducted on 50 patients who underwent facial augmentation using combined transplantation of high-density fat (HDF) and condensed low-density fat (CLDF) and 25 patients who underwent conventional Coleman fat grafting. Coleman fat was harvested by standard technique and the adipose tissue was divided into HDF and CLDF fractions through centrifugation. Subsequently, the low-density fat fraction was subjected to a process involving physical disruption followed by additional centrifugation to obtain CLDF. The CLDF fraction was consequently injected into the pre-SMAS subcutaneous layer of the superficial fat compartments. Patient satisfaction was evaluated using a typical Likert scale. Photographs were taken and imageological examinations were performed before and after treatment. RESULT: The CLDF+HDF grafting group demonstrated a significantly shorter duration of swelling (6.0 ± 1.2 to 12.6 ± 3.3 days) and higher level of patient satisfaction when compared to the Coleman fat group. No serious complications were observed among all the patients who received the injections. CONCLUSION: The use of this new treatment approach allows for precise fat transplantation in facial regions. The use of high-concentration fat filling for deep facial layers and CLDF filling for superficial layers is a safe and effective treatment plan for facial rejuvenation. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

CPhaMAS: An online platform for pharmacokinetic data analysis based on optimized parameter fitting algorithm.

BACKGROUND AND OBJECTIVE: Clinical pharmacological modeling and statistical analysis software is an essential basic tool for drug development and personalized drug therapy. The learning curve of current basic tools is steep and unfriendly to beginners. The curve is even more challenging in cases of significant individual differences or measurement errors in data, resulting in difficulties in accurately estimating pharmacokinetic parameters by existing fitting algorithms. Hence, this study aims to explore a new optimized parameter fitting algorithm that reduces the sensitivity of the model to initial values and integrate it into the CPhaMAS platform, a user-friendly online application for pharmacokinetic data analysis. METHODS: In this study, we proposed an optimized Nelder-Mead method that reinitializes simplex vertices when trapped in local solutions and integrated it into the CPhaMAS platform. The CPhaMAS, an online platform for pharmacokinetic data analysis, includes three modules: compartment model analysis, non-compartment analysis (NCA) and bioequivalence/bioavailability (BE/BA) analysis. Our proposed CPhaMAS platform was evaluated and compared with existing WinNonlin. RESULTS: The platform was easy to learn and did not require code programming. The accuracy investigation found that the optimized Nelder-Mead method of the CPhaMAS platform showed better accuracy (smaller mean relative error and higher R2) in two-compartment and extravascular administration models when the initial value was set to true and abnormal values (10 times larger or smaller than the true value) compared with the WinNonlin. The mean relative error of the NCA calculation parameters of CPhaMAS and WinNonlin was <0.0001 %. When calculating BE for conventional, high-variability and narrow-therapeutic drugs. The main statistical parameters of the parameters Cmax, AUCt, and AUCinf in CPhaMAS have a mean relative error of <0.01% compared to WinNonLin. CONCLUSIONS: In summary, CPhaMAS is a user-friendly platform with relatively accurate algorithms. It is a powerful tool for analysing pharmacokinetic data for new drug development and precision medicine.

Retina images classification based on 2D empirical mode decomposition and multifractal analysis.

Diabetic retinopathy is an ocular disease caused by long-term damage to the retina due to high blood sugar levels. Elevated blood sugar can impair the microvasculature in the retina, leading to vascular abnormalities and the formation of abnormal new blood vessels. These changes can manifest in the retina as hemorrhages, leaks, vessel dilation, retinal edema, and retinal detachment. The retinas of individuals with diabetes exhibit different morphologies compared to those without the condition. Most histological images cannot be accurately described using traditional geometric shapes or methods. Therefore, this study aims to evaluate and classify the morphology of retinas with varying degrees of severity using multifractal geometry. In the initial experiments, two-dimensional empirical mode decomposition was employed to extract high-frequency detailed features, and the classification process was based on the most relevant features in the multifractal spectrum associated with disease factors. To eliminate less significant features, the random forest algorithm was utilized. The proposed method achieved an accuracy of 96%, sensitivity of 96%, and specificity of 95%.

Electronic structures and quantum capacitance of twisted bilayer graphene with defects based on three-band tight-binding model.

Twisted bilayer graphene (tBLG) with C vacancies would greatly improve the density of states (DOS) around the Fermi level (EF) and quantum capacitance; however, the single-band tight-binding model only considering pz orbitals cannot accurately capture the low-energy physics of tBLG with C vacancies. In this work, a three-band tight-binding model containing three p orbitals of C atoms is proposed to explore the modulation mechanism of C vacancies on the DOS and quantum capacitance of tBLG. We first obtain the hopping integral parameters of the three-band tight-binding model, and then explore the electronic structures and the quantum capacitance of tBLG at a twisting angle of θ = 1.47° under different C vacancy concentrations. The impurity states contributed by C atoms with dangling bonds located around the EF and the interlayer hopping interaction could induce band splitting of the impurity states. Therefore, compared with the quantum capacitance of pristine tBLG (∼18.82 µF cm-2) at zero bias, the quantum capacitance is improved to ∼172.76 µF cm-2 at zero bias, and the working window with relatively large quantum capacitance in the low-voltage range is broadened in tBLG with C vacancies due to the enhanced DOS around the EF. Moreover, the quantum capacitance of tBLG is further increased at zero bias with an increase of the C vacancy concentration induced by more impurity states. These findings not only provide a suitable multi-band tight-binding model to describe tBLG with C vacancies but also offer theoretical insight for designing electrode candidates for low-power consumption devices with improved quantum capacitance.

Type IV Collagen Promotes Adipogenic Differentiation of Adipose Stem Cells.

Type IV collagen is a major component of the extracellular matrix in adipose tissue. It is secreted during the lipogenic differentiation of mesenchymal stem cells, but its direct impact and mechanism on the differentiation of adipose-derived stem cells (ASCs) into lipids are unclear. In this study, ASCs were obtained from human liposuction samples and cultured. Lipogenic induction of ASCs was achieved using lipogenic induction medium. Immunofluorescence analysis revealed differential expression of type IV collagen during the early and late stages of adipogenic induction, displaying a distinct morphological encapsulation of ASCs. Silencing of type IV collagen using siRNA resulted in a significant decrease in adipogenic capacity, as indicated by reduced lipid droplet formation and downregulation of adipogenic-related gene transcription. Conversely, supplementation of the culture medium with synthetic type IV collagen demonstrated enhanced adipogenic induction efficiency, accompanied by upregulation of YAP/TAZ protein expression and its downstream target gene transcription. Furthermore, inhibition of the YAP/TAZ pathway using the inhibitor Blebbistatin attenuated the functionality of type IV collagen, leading to decreased lipid droplet formation and downregulation of adipocyte maturation-related gene expression. These findings highlight the crucial role of type IV collagen in promoting adipogenic differentiation of ASCs and suggest its involvement in the YAP/TAZ-mediated Hippo pathway.No Level Assigned This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Lipolysis inhibition improves the survival of fat grafts through ameliorating lipotoxicity and inflammation.

Fat grafting is a promising technique for correcting soft tissue abnormalities, but oil cyst formation and graft fibrosis frequently impede the therapeutic benefit of fat grafting. The lipolysis of released oil droplets after grafting may make the inflammation and fibrosis in the grafts worse; therefore, by regulating adipose triglyceride lipase (ATGL) via Atglistatin (ATG) and Forskolin (FSK), we investigated the impact of lipolysis on fat grafts in this study. After being removed from the mice and chopped into small pieces, the subcutaneous fat from wild-type C57BL/6J mice was placed in three different solutions for two hours: serum-free cell culture medium, culture medium+FSK (50 µM), and culture medium+ATG (100 µM). Following centrifugation to remove water and free oil droplets, 0.3 mL of the fat particles per mouse was subcutaneously injected into the back of mice. Additionally, the subcutaneous fat grafting area was immediately injected with PBS (control group), ATG (30 mg/kg), and FSK (15 mg/kg) following fat transplantation. Detailed cellular events after grafting were investigated by histological staining, real-time polymerase chain reaction, immunohistochemistry/immunofluorescent staining, and quantification. Two weeks after grafting, grafts treated with ATG showed lower expression of ATGL and decreased mRNA levels of TNFα and IL-6. In contrast, grafts treated with ATG showed elevated expression levels of IL-4 and IL-13 compared to the control grafts. In addition, fewer apoptotic cells and oil cysts were observed in ATG grafts. Meanwhile, a higher CD206+/CD68+ ratio of macrophages and more CD31+ vascular endothelial cells existed in the 2-month ATG grafts. In comparison to the control, ATG treatment improved the volume retention of grafts, and decreased graft fibrosis and oil cyst formation. By preventing oil droplet lipolysis, pharmacological suppression of ATGL shielded adipocytes from lipotoxicity following grafting. Additionally, ATG ameliorated the apoptosis and inflammation brought on by adipocyte death and oil droplet lipolysis in grafted fat. These all indicate that lipolysis inhibition improved transplanted fat survival and decreased the development of oil cysts and graft fibrosis, offering a potential postoperative pharmacological intervention for bettering fat grafting.

Robust Dual-Modal Speech Keyword Spotting for XR Headsets.

While speech interaction finds widespread utility within the Extended Reality (XR) domain, conventional vocal speech keyword spotting systems continue to grapple with formidable challenges, including suboptimal performance in noisy environments, impracticality in situations requiring silence, and susceptibility to inadvertent activations when others speak nearby. These challenges, however, can potentially be surmounted through the cost-effective fusion of voice and lip movement information. Consequently, we propose a novel vocal-echoic dual-modal keyword spotting system designed for XR headsets. We devise two different modal fusion approches and conduct experiments to test the system's performance across diverse scenarios. The results show that our dual-modal system not only consistently outperforms its single-modal counterparts, demonstrating higher precision in both typical and noisy environments, but also excels in accurately identifying silent utterances. Furthermore, we have successfully applied the system in real-time demonstrations, achieving promising results. The code is available at https://github.com/caizhuojiang/VE-KWS.

G-site residue S67 is involved in the fungicide-degrading activity of a tau class glutathione S-transferase from Carica papaya.

Thiram is a toxic fungicide extensively used for the management of pathogens in fruits. Although it is known that thiram degrades in plant tissues, the key enzymes involved in this process remain unexplored. In this study, we report that a tau class glutathione S-transferase (GST) from Carica papaya can degrade thiram. This enzyme was easily obtained by heterologous expression in Escherichia coli, showed low promiscuity toward other thiuram disulfides, and catalyzed thiram degradation under physiological reaction conditions. Site-directed mutagenesis indicated that G-site residue S67 shows a key influence for the enzymatic activity toward thiram, while mutation of residue S13, which reduced the GSH oxidase activity, did not significantly affect the thiram-degrading activity. The formation of dimethyl dithiocarbamate, which was subsequently converted into carbon disulfide, and dimethyl dithiocarbamoylsulfenic acid as the thiram degradation products suggested that thiram undergoes an alkaline hydrolysis that involves the rupture of the disulfide bond. Application of the GST selective inhibitor 4-chloro-7-nitro-2,1,3-benzoxadiazole reduced papaya peel thiram-degrading activity by 95%, indicating that this is the main degradation route of thiram in papaya. GST from Carica papaya also catalyzed the degradation of the fungicides chlorothalonil and thiabendazole, with residue S67 showing again a key influence for the enzymatic activity. These results fill an important knowledge gap in understanding the catalytic promiscuity of plant GSTs and reveal new insights into the fate and degradation products of thiram in fruits.

Composite Microparticles of Fat Graft and GFR Matrigel Improved Volume Retention by Promoting Cell Migration and Vessel Regeneration.

BACKGROUND: The retention volume of autologous fat grafts decreases after transplantation due to limited nutrition infiltration and insufficient blood supply. Structural fat grafts and the 3M (multipoint, multitunnel, and multilayer) injection technique have been considered to improve the survival of grafts; however, it is difficult for surgeons to practice in the clinic because grafts tend to gather into a cluster, especially in large volume fat grafting. Therefore, we hypothesize that prefabricated microparticle fat grafts (PFMG) may improve the retention rate. METHODS: The C57BL/6 mouse fat particles were embedded in growth factor-reduced (GFR)-Matrigel to detect cell migration by immunofluorescence staining in vitro. PFMG was prepared by mixing mouse fat particles and GFR Matrigel in a 1:1 volume ratio and injected subcutaneously into C57BL/6 mice. Fat particles mixed with PBS in equal volume served as control group. The grafts were harvested at 1, 4, 8, and 12 weeks after sacrifice. The retention rate of grafts at each time point was measured, and the structural alterations were detected by SEM. Fat necrosis and blood vessel density were evaluated by histological analysis. RESULTS: CD34+ cells are migrated from the PFMG and formed a tree-like tubular network in the in vitro study. The retention rate was higher in the PFMG group than in the control group at week 12 (38% vs. 30%, p < 0.05). After transplantation, the dissociated structure of fat particles was maintained in PFMG by SEM analysis. Histological analysis of PFMG confirmed less fat necrosis and more blood vessel density in the PFMG group at the early stage than in the control group. The GFR Matrigel was displaced by adipose tissue with time. CONCLUSIONS: In this study, we developed a novel fat grafting method, PFMG that dispersed fat grafts and maintained the structure after transplantation. High volume retention volume of PFMG was achieved by promoting cell migration and vessel regeneration. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Inflammation-mediated metabolic regulation in adipose tissue.

Chronic inflammation of adipose tissue is a prominent characteristic of many metabolic diseases. Lipid metabolism in adipose tissue is consistently dysregulated during inflammation, which is characterized by substantial infiltration by proinflammatory cells and high cytokine concentrations. Adipose tissue inflammation is caused by a variety of endogenous factors, such as mitochondrial dysfunction, reactive oxygen species (ROS) production, endoplasmic reticulum (ER) stress, cellular senescence, ceramides biosynthesis and mediators of lipopolysaccharides (LPS) signaling. Additionally, the gut microbiota also plays a crucial role in regulating adipose tissue inflammation. Essentially, adipose tissue inflammation arises from an imbalance in adipocyte metabolism and the regulation of immune cells. Specific inflammatory signals, including nuclear factor-κB (NF-κB) signaling, inflammasome signaling and inflammation-mediated autophagy, have been shown to be involved in the metabolic regulation. The pathogenesis of metabolic diseases characterized by chronic inflammation (obesity, insulin resistance, atherosclerosis and nonalcoholic fatty liver disease [NAFLD]) and recent research regarding potential therapeutic targets for these conditions are also discussed in this review.

Silencing of secreted phosphoprotein 1 attenuates sciatic nerve injury-induced neuropathic pain: Regulating extracellular signal-regulated kinase and neuroinflammatory signaling pathways.

BACKGROUND: Neuropathic pain (NP) is a chronic pathological pain that affects the quality of life and is a huge medical burden for affected patients. In this study, we aimed to explore the effects of secreted phosphoprotein 1 (SPP1) on NP. METHODS: We established a chronic constriction injury (CCI) rat model, knocked down SPP1 via an intrathecal injection, and/or activated the extracellular signal-regulated kinase (ERK) pathway with insulin-like growth factor 1 (IGF-1) treatment. Pain behaviors, including paw withdrawal threshold (PWT), paw withdrawal latency (PWL), lifting number, and frequency, were assessed. After sacrificing rats, the L4-L5 dorsal root ganglion was collected. Then, SPP1 levels were determined using quantitative polymerase chain reaction (qPCR) and western blot analysis. The levels of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-6, IL-10, epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and transforming growth factor (TGF)-ß were determined using qPCR and enzyme-linked immunosorbent assay. The levels of ERK pathway factors were determined via western blot analysis. RESULTS: We found that CCI decreased PWT and PWL, increased the lifting number and frequency, and upregulated SPP1 levels. The loss of SPP1 reversed these CCI-induced effects. Additionally, CCI upregulated IL-1ß, TNF-α, IL-6, EGF, and VEGF levels, downregulated TGF-ß levels, and activated the ERK pathway, while silencing of SPP1 abrogated these CCI-induced effects. Moreover, IGF-1 treatment reversed the effects of SPP1 loss. CONCLUSIONS: The data indicate that silencing SPP1 attenuates NP via inactivation of the ERK pathway, suggesting that SPP1 may be a promising target for NP treatment.

Neuroprotective effects of exosomes derived from bone marrow mesenchymal stem cells treated by Musk Ketone on ischemic stroke rats.

OBJECTIVES: Ischemic stroke (IS) is a leading cause of morbidity and mortality globally. This study aimed to investigate the role of exosomes (Exo) derived from bone marrow mesenchymal stem cells (BMSCs) treated with Musk Ketone (Mus treated-Exo) in the development of IS injury. METHODS: BMSCs were pretreated with 10 µM Mus for 36 hours, and Exo derived from these Mus-treated BMSCs (Mus-treated Exo) were extracted. Rats with middle cerebral artery occlusion (MCAO) were administered either 2 mg/kg of control Exo (Ctrl-Exo), 2 mg/kg of Mus treated-Exo, or 10 µM Mus. Neurological deficit and cerebral infarction in the MCAO rats were assessed utilizing neurological scores and TTC staining. Neuronal apoptosis, activation of microglia/macrophages, and inflammation were evaluated through TUNEL staining, immunofluorescence staining, and western blot analysis, respectively. RESULTS: Our findings revealed that Mus-treated Exo possessed a more pronounced neuroprotective effect on MCAO rats when compared to Ctrl-Exo and Mus treatment alone. Specifically, Mus treated-Exo effectively ameliorated neurological function, reduced the volume of cerebral infarction, and diminished hemispheric swelling in MCAO rats. Moreover, it inhibited neuronal apoptosis and activation of microglia/macrophages, promoted the expression of the anti-apoptotic protein Bcl-2 while decreasing the expression of pro-apoptotic protein Bax, Cleaved-caspase 3, and pro-inflammatory factors IL-6 and COX-2. CONCLUSIONS: The findings imply that Mus treated-Exo could confer neuroprotection in rats affected by IS, potentially by attenuating apoptosis and neuroinflammation. The underlying mechanisms, however, warrant further investigation. Mus treated-Exo shows potential as a new therapeutic strategy for IS.

Osteopontin Promotes Angiogenesis in the Spinal Cord and Exerts a Protective Role Against Motor Function Impairment and Neuropathic Pain after Spinal Cord Injury.

STUDY DESIGN: Basic science study using a hemi-section spinal cord injury (SCI) model. OBJECTIVE: We sought to assess the effect of blocking Osteopontin (OPN) up-regulation on motor function recovery and pain behavior after SCI and to further investigate the possible downstream target of OPN in the injured spinal cord. SUMMARY OF BACKGROUND DATA: OPN is a noncollagenous extracellular matrix protein widely expressed across different tissues. Its expression substantially increases following SCI. A previous study suggested that this protein might contribute to locomotor function recovery after SCI. However, its neuroprotective potential was not fully explored, nor were the underlying mechanisms. METHODS: We constructed a SCI mouse model and analyzed the expression of OPN at different time points, and the particular cell distribution in the injured spinal cord. Then, we blocked OPN up-regulation with lentivirus delivering siRNA targeting OPN specifically and examined its effect on motor function impairment and neuropathic pain after SCI. The underlying mechanisms were explored in the OPN-knockdown mice model and cultured vascular endothelial cells. RESULTS: The proteome study revealed that OPN was the most dramatically increased protein following SCI. OPN in the spinal cord was increased significantly 3 weeks after SCI. Suppressing the OPN up-regulation via siRNA exacerbated motor function impairment and neuropathic pain. Additionally, SCI resulted in an increase in the vascular endothelial growth factor (VEGF), AKT phosphorylation, and angiogenesis within the spinal cord, all of which were curbed by OPN reduction. Similarly, OPN knockdown suppressed VEGF expression, AKT phosphorylation, cell migration, invasion, and angiogenesis in cultured vascular endothelial cells. CONCLUSION: OPN demonstrates a protective influence against motor function impairment and neuropathic pain following SCI. This phenomenon may result from the pro-angiogenetic effect of OPN, possibly due to activation of the VEGF and/or AKT pathways.

Adipose-derived stem cells in immune-related skin disease: a review of current research and underlying mechanisms.

Adipose-derived stem cells (ASCs) are a critical adult stem cell subpopulation and are widely utilized in the fields of regenerative medicine and stem cell research due to their abundance, ease of harvest, and low immunogenicity. ASCs, which are homologous with skin by nature, can treat immune-related skin diseases by promoting skin regeneration and conferring immunosuppressive effects, with the latter being the most important therapeutic mechanism. ASCs regulate the immune response by direct cell-cell communication with immune cells, such as T cells, macrophages, and B cells. In addition to cell-cell interactions, ASCs modulate the immune response indirectly by secreting cytokines, interleukins, growth factors, and extracellular vesicles. The immunomodulatory effects of ASCs have been exploited to treat many immune-related skin diseases with good therapeutic outcomes. This article reviews the mechanisms underlying the immunomodulatory effects of ASCs, as well as progress in research on immune-related skin diseases.

Low-intensity ultrasound-assisted adaptive laboratory evolution of Bacillus velezensis for enhanced production of peptides.

This work aimed to explore low-intensity ultrasound-assisted adaptive laboratory evolution (US-ALE) of Bacillus velezensis and fermentation performance of mutant strains were investigated by nitrogen transformation metabolism. Results showed ultrasound accelerated the process of adaptive evolution and enhanced cell dry weight, amylase and protease activity of mutant strains, accompanied with the improved transformation abilities of NO-3-N to NH4+-N. Compared with original strain, the total peptide-N, peptide-N (<3 kDa) and autolytic peptide-N of mutant strains increased by the maximum 23.17%, 66.07% and 30.30%, respectively, based on ideal fermentation medium. According to the actual liquid-state fermentation of soybean meal and corn gluten meal with mutant strains, the highest peptide yields of 50.63% and 23.67% were noticed in mutant strain US-ALE-BV3, accompanied with the improved amino acid composition by bacterial autolysis technology. Thus, this study showed that low-intensity ultrasound could accelerate the process of adaptive evolution and US-ALE will provide more possibilities for modifying fermentation strains.