Density Of Nuclei Research Articles

Trophoblast Proliferation is higher in Female than in Male Preeclamptic Placentas

IntroductionPreeclampsia (PE) is a pregnancy-specific hypertensive disorder with inflammatory complications. There are no known placental histopathological features, which are unique to PE. It is often pooled with the fetal growth restriction (FGR) under a single umbrella pathophysiology, the maternal vascular malperfusion (MVM). The aim of this study is to assess the villous trophoblast and the villous tree quantitatively in PE placentas and to identify morpholgical correlates unique to PE. Methods20 PE placentas (10 female and 10 male) and 20 Control placentas (10 female and 10 male) were included in the study. The villous trophoblast and the villous tree were assessed quantitatively by Stereology and 3D Microscopy. For Stereology measurements, the villous tree was classified in contractile and non-contractile parts based on immunohistochemical detection of perivascular myofibroblasts. ResultsThe density of proliferative trophoblast nuclei is increased, whereas the density of non-proliferative trophoblast nuclei is decreased in female PE placentas. The male PE placentas do not show this effect. Though no significant difference in the diffusion distance was observed, the non-contractile villi and the fetal vessels inside show a significantly reduced volume in PE placentas. The branching index of the villous tree is lower in PE placentas in general. However, in female PE placentas the deviation is accentuated. ConclusionIn PE, the villous trophoblast shows a sexually dimorphic alteration in the density of proliferative and non-proliferative nuclei, which is inherently different from FGR.

Supraspinatus Muscle Regeneration Following Rotator Cuff Tear: A Study of the Biomarkers Pax7, MyoD, and Myogenin.

The success of rotator cuff tendon repair relies on both tendon healing and muscle recovery. The objective of this descriptive study was to investigate the regenerative potential of the supraspinatus muscle in rotator cuff tear conditions by quantifying the expression of Pax7, MyoD, and myogenin, basic factors that regulate myogenesis. Muscle biopsies were collected from thirty-three patients aged 34 to 73 years who underwent surgery for a rotator cuff tear affecting the supraspinatus muscle. Among these patients, twenty-seven percent were women, and the age of the lesions ranged from 2 to 72 months post-initial trauma. Biopsies were harvested from the supraspinatus muscle at the end closest to the tendon, and control biopsies were harvested from the ipsilateral deltoid muscle. The densities of immunohistochemically stained Pax7+, MyoD+, and myogenin+ nuclei/mm2 were used to estimate the myogenic potential of the muscle. Adjustments were made for patient age and lesion age. We found increased density of MyoD+ and myogenin+ cells in supraspinatus muscles compared to deltoid muscles (p < 0.001 and p = 0.003, respectively). Regression analyses that combined the density of positive nuclei with patient age showed a continuous increase in Pax7 with age but also a reduction of MyoD and myogenin in older patients. When combined with lesion age, there was a decline in the density of all myogenic markers after an initial rise. Pax7 density continued to be higher in supraspinatus compared to the deltoid muscle, but the density of MyoD and myogenin terminally dropped to a density lower than in the deltoid. Our findings suggest that the supraspinatus muscle in tear conditions showed signs of initial activation of muscle regeneration. When compared to the unaffected deltoid muscle, an apparent reduction in capacity to progress to full muscle fiber maturity was also demonstrated. This pattern of inhibited myogenesis seemed to increase with both patient age and lesion age. Our results on muscle regenerative capacity indicate that younger patients with rotator cuff tears have better chances of muscle recovery and may benefit from early surgical reconstruction.

Entropies, level-density parameters and fission probabilities along the triaxially- and axially-symmetric fission paths in 296Lv

We investigate the variation of statistical properties of the fissile nucleus, especially entropy, and nuclear level density, along different fission paths. The calculations were focused on comparing axial and triaxial trajectories leading to fission of 296Lv. We observe that change of shell effects and their suppression rates with deformation can substantially influence fission dynamics. Furthermore, the fission process exhibits iso-entropic behavior at high excitation energies, while pronounced entropy variations are observed at lower energies. We derive a deformation-dependent level density parameter that plays a critical role in estimating the survival probability of a superheavy nucleus. The competition between different fission paths was further studied by employing a master equation approach, thereby demonstrating the critical role of entropy and thermodynamic properties in shaping fission dynamics within multidimensional deformation spaces.

Interferon-β-Induced Injury During Pediatric Muscle Differentiation: Insight Into Juvenile Dermatomyositis Pathogenesis.

Juvenile dermatomyositis (JDM) involves up-regulated type I interferons (IFNs), including IFNβ, yet pathologic mechanisms remain poorly understood. We aimed to characterize the functional and structural effects of IFNβ on in vitro human pediatric myoblast growth and differentiation in a three-dimensional skeletal muscle model (myobundles). Myobundles fabricated from myoblasts of a healthy pediatric donor were exposed to IFNβ at 0 to 5,600 IU/mL during growth (days 1-4), differentiation (days 4-11), and/or mature (days 11-18) periods. To assess myobundle structure and function, contractile force, kinetics, and fatigue were measured at day 18 with subsequent immunohistochemistry. Myobundles were not functionally affected by IFNβ exposure during growth period alone. However, when IFNβ exposure continued through differentiation, myobundles became dysfunctional (P < 0.0001). IFNβ during differentiation or mature periods alone resulted in dose-dependent decreases in contractility, with greater decrease in the differentiation alone group (P < 0.0001). Twitch kinetics and fatigue remained largely unchanged when myobundles were exposed to IFNβ only during growth, yet twitch time slowed (P < 0.005) and fatigue decreased (P < 0.002) when myobundles were exposed during differentiation or mature stages alone. Nuclei density and myofiber size and organization also decreased when IFNβ was added during differentiation period alone. IFNβ decreases pediatric myobundle contractile function most significantly during differentiation of myoblasts to myotubes. Function is not affected when IFNβ exposure is limited to myoblast proliferation alone. These findings implicate a pathologic role for IFNβ in JDM by impairing myoblast differentiation, leading to subsequent loss of function and ongoing need for muscle regeneration and repair.

Histological and photoacoustic evaluation of rectal cancer after neoadjuvant therapy using microvascular density.

As non-operative management of rectal cancer proliferates, re-staging and surveillance methods are critical in selecting appropriate patients for organ preservation versus proctectomy. In previous work, the authors have shown that transrectal acoustic resolution photoacoustic microscopy (ARPAM) co-registered with ultrasound can differentiate residual cancer from complete tumoural response to neoadjuvant therapy. We hypothesize that these findings are due to changes in microvascular density (MVD). Patients with rectal adenocarcinoma who underwent neoadjuvant therapy, transrectal photoacoustic imaging and resection were included. We first compared immunohistochemical staining with erythroblast transformation-specific-related gene (ERG) immunostain to standard CD31 to confirm adequate identification of endothelium. Tissue sections from identical blocks were stained with CD31 and ERG, and then a correlation was calculated between manually labelled CD31-stained vessels and ERG nuclei density. Second, representative tissue blocks from responders, partial responders and non-responders were stained with ERG. ERG nuclei density was quantified as a proxy for MVD. CD31 MVD and ERG nuclei density were strongly correlated (R2 = 0.87; P < 0.01). In the tumour bed of patients after neoadjuvant therapy, MVD of complete responders (599 nuclei/mm2; 95% CI 434-764) is significantly higher (P < 0.01) than that of partial responders (185 nuclei/mm2; 95% CI 64-306) and non-responders (117 nuclei/mm2; 95% CI 42-192). No significant difference was found between the partial responders and non-responders (P = 0.60). Microvascular density appears highest in cases of complete tumour response to neoadjuvant therapy, similar to normal rectal tissue. The histological microvascular patterns seen in treated tissue may explain the imaging patterns seen in photoacoustic microscopy.

Interfacial crystallization behavior and properties of T1100-grade carbon fiber reinforced PEEK composites

As a semi-crystalline resin, the crystallization behavior of Polyether ether ketone at the interface between carbon fiber and resin matrix profoundly affects the interfacial properties of carbon fiber-reinforced PEEK composite. Therefore, the research on the interfacial crystallization behavior of CF/PEEK composite is of great significance. Aiming at Chinese-made T1100-grade carbon fiber and PEEK resin matrix, the effects of cooling rate and sizing agent on the interfacial crystallization behavior of T1100-grade carbon fiber/PEEK were studied by POM and DSC, and the IFSS was tested by microdebond. The experimental results show that the increase of the cooling rate and the removal of the sizing agent can improve the nucleation ability of PEEK and promote the interfacial crystallization of PEEK. PEEK starts to form transcrystallization, when the nucleus density is increased to about 0.07/μm. The interfacial crystallization behavior has an effect on the interfacial properties. The IFSS increases with increasing cooling rate and removal of sizing agent.

Regulation of nucleation and crystallization for blade-coating large-area CsPbBr3 perovskite light-emitting diodes

Metal halide perovskite light-emitting diodes (PeLEDs) and large-area perovskite color conversion layers for liquid crystal display exhibit great potential in the field of illumination and display. Blade-coating method stands out as a highly suitable technique for fabricating large-scale films, albeit with challenges such as uneven nucleation coverage and non-uniformity crystallization process. In this work, we developed an in-situ characterization measurement system to monitor the perovskite nucleation, and crystallization process. By incorporating formamidine acetate (FAAc) into perovskite precursor solutions, the nucleation rate and nuclei density of perovskite were increased, leading to more uniform nucleation. In addition, we inserted a layer of [2-(9H-carbazol-9-yl)ethyl] phosphonic acid above the poly(9-vinylcarbazole) hole transport layer. This layer acts as an anchor for the perovskite nano-crystal nuclei formed in the precursor, enhancing the steric hindrance of the solute and subsequently slowing down the crystal growth rate, thereby improving crystal quality. Based on these improvements, large-area perovskite nano-polycrystalline films with significantly improved uniformity and enhanced photoluminescence quantum yield were obtained. A small-area PeLED (2 mm × 2 mm) with a maximum external quantum efficiency of 25.91% was realized, marking the highest record of PeLED prepared by blade-coating method to date. An ultra-large-area PeLED (5 cm × 7 cm) was also prepared, which is the largest PeLED prepared by the solution method reported so far.

Computing the QRPA level density with the finite amplitude method

We describe a new algorithm to calculate the vibrational nuclear level density of an atomic nucleus. Fictitious perturbation operators that probe the response of the system are generated by drawing their matrix elements from some probability distribution function. We use the Finite Amplitude Method to explicitly compute the response for each such sample. With the help of the Kernel Polynomial Method, we build an estimator of the vibrational level density and provide the upper bound of the relative error in the limit of infinitely many random samples. The new algorithm can give accurate estimates of the vibrational level density. Since it is based on drawing multiple samples of perturbation operators, its computational implementation is naturally parallel and scales like the number of available processing units.

A study of tin electrodeposition from ethaline: The electrode material effect

AbstractThis article studies the influence of electrode material on tin (Sn) electrodeposition from deep eutectic solvent. The Sn electrodeposition from ethaline‐based electrolyte onto glassy carbon (GC) and Pt substrates has been studied using cyclic voltammetry and chronoamperometry. The patterns and parameters of Sn nucleation and growth processes have been determined by means of Scharifker and Hills and Scharifker–Mostany models. Results show that Sn nucleation onto GCE follows instantaneous 3D nucleation, while in the case of PtE, it is controlled by adsorption, instantaneous 3D nucleation, and residual water reduction. The growth mechanism is diffusion‐controlled for both electrodes. The parameters of Sn electrodeposition onto GCE and PtE such as diffusion coefficient (D), nucleation rate (A), and active site density of Sn nuclei (No) are evaluated. The results showed that A and No increase linearly as the deposition potential is displaced towards more electronegative values while D is almost unchanged, regardless of the involved working electrode. The morphology and the structure of the electrodeposited Sn are also discussed based on scanning electron microscopy, X‐ray diffraction, and energy‐dispersive X‐ray spectroscopy investigations.

Alterations of Liver Morphology in Senescent Rats.

Age-related liver changes can have important implications for health and metabolic function. This study aimed to describe the morphoquantitative alterations of the liver in senescent rats compared to adult rats. Twelve male rats were used, divided into 6-month-old adults (group A) and 36-month-old senescent rats (group S). Morphometric and histopathological studies, quantification of collagen types I and III, and stereological analyses were performed to determine the volume density of mononucleated (VvhepM) and binucleated (VvhepB) hepatocyte nuclei, surface area density (SvhepM), and number density (NvhepM) of mononucleated hepatocyte nuclei. The findings reveal an alteration of the normal liver tissue architecture in senescent rats and the presence of inflammatory lesions and fibrosis. In addition, there was a decrease in body and liver mass and volume. Group S showed a significant reduction in VvhepM and NvhepM; however, SvhepM was significantly higher. No significant differences were noted in the percentage of binucleated hepatocytes between the two groups. This study reveals substantial morphological changes in the aging liver, with possible functional implications. More research is needed on the underlying mechanisms and their consequences at older ages.

Control nucleation for strong and tough crystalline hydrogels with high water content

Hydrogels, provided that they integrate strength and toughness at desired high content of water, promise in load-bearing tissues such as articular cartilage, ligaments, tendons. Many developed strategies impart hydrogels with some mechanical properties akin to natural tissues, but compromise water content. Herein, a strategy deprotonation-complexation-reprotonation is proposed to prepare polyvinyl alcohol hydrogels with water content as high as ~80% and favorable mechanical properties, including tensile strength of 7.4 MPa, elongation of around 1350%, and fracture toughness of 12.4 kJ m−2. The key to water holding yet improved mechanical properties lies in controllable nucleation for refinement of crystalline morphology. With nearly constant water content, mechanical properties of as-prepared hydrogels are successfully tailored by tuning crystal nuclei density via deprotonation degree and their distribution uniformity via complexation temperature. This work provides a nucleation concept to design robust hydrogels with desired water content, holding implications for practical application in tissue engineering.

Viscoelastic properties of colorectal liver metastases reflect tumour cell viability

BackgroundColorectal cancer is the third most common tumour entity in the world and up to 50% of the patients develop liver metastases (CRLM) within five years. To improve and personalize therapeutic strategies, new diagnostic tools are urgently needed. For instance, biomechanical tumour properties measured by magnetic resonance elastography (MRE) could be implemented as such a diagnostic tool. We postulate that ex vivo MRE combined with histological and radiological evaluation of CRLM could provide biomechanics-based diagnostic markers for cell viability in tumours.Methods34 CRLM specimens from patients who had undergone hepatic resection were studied using ex vivo MRE in a frequency range from 500 Hz to 5300 Hz with increments of 400 Hz. Single frequency evaluation of shear wave speed and wave penetration rate as proxies for stiffness and viscosity was performed, along with rheological model fitting based on the spring-pot model and powerlaw exponent α, ranging between 0 (complete solid behaviour) and 1 (complete fluid behaviour). For histological analysis, samples were stained with H&E and categorized according to the degree of regression. Quantitative histologic analysis was performed to analyse nucleus size, aspect ratio, and density. Radiological response was assessed according to RECIST-criteria.ResultsFive samples showed major response to chemotherapy, six samples partial response and 23 samples no response. For higher frequencies (> 2100 Hz), shear wave speed correlated significantly with the degree of regression (p ≤ 0.05) indicating stiffer properties with less viable tumour cells. Correspondingly, rheological analysis of α revealed more elastic-solid tissue properties at low cell viability and major response (α = 0.43 IQR 0.36, 0.47) than at higher cell viability and no response (α = 0.51 IQR 0.48, 0.55; p = 0.03). Quantitative histological analysis showed a decreased nuclear area and density as well as a higher nuclear aspect ratio in patients with major response to treatment compared to patients with no response (all p < 0.05).DiscussionOur results suggest that MRE could be useful in the characterization of biomechanical property changes associated with cell viability in CRLM. In the future, MRE could be applied in clinical diagnosis to support individually tailored therapy plans for patients with CRLM.

Sn nucleation and growth from Sn(II) dissolved in ethylene glycol: Electrochemical behavior and temperature effect

Thermodynamic and kinetic aspects of Sn nucleation and growth processes onto a glassy carbon electrode from SnCl2·2H2O dissolved in ethylene glycol solutions were studied. Typical reduction and oxidation peaks observed in voltammograms have demonstrated the capability of ethylene glycol solutions to electrodeposit Sn. The temperature-dependence of diffusion coefficient values derived from potentiodynamic and potentiostatic studies helped to determine and validate estimations of the activation energy for Sn(II) bulk diffusion. Chronoamperometric results have identified that, the suitable model to describe the early stage of Sn electrodeposition could be composed of Sn three-dimensional nucleation and diffusion-controlled growth and water reduction contributions, which was duly validated by theoretical and experimental approaches. From the model, typical kinetic parameters such as the nucleation frequency of Sn (A), number density of Sn nuclei (N0), and diffusion coefficient of Sn(II) ions (D), were determined. The presence of Sn nuclei with excellent quality and their structures were verified using SEM, EDX, and XRD techniques.

Multiline observations of hydrogen, helium, and carbon radio-recombination lines toward Orion A: A detailed dynamical study and direct determination of physical conditions

We present a study of hydrogen, helium, and carbon millimeter-wave radio-recombination lines (RRLs) toward 10 representative positions throughout the Orion Nebula complex, using the Yebes 40 m telescope in the Q band (31.3 GHz to 50.6 GHz) at an angular resolution of about 45″ (~0.09 pc). The observed positions include the Orion Nebula (M42) with the Orion Molecular Core 1, M43, and the Orion Molecular Core 3 bordering on NGC 1973, 1975, and 1977. While hydrogen and helium RRLs arise in the ionized gas surrounding the massive stars in the Orion Nebula complex, carbon RRLs stem from the neutral gas of the adjacent photo-dissociation regions (PDRs). The high velocity resolution (0.3 km s−1) enables us to discern the detailed dynamics of the RRL emitting neutral and ionized gas. We compare the carbon RRLs with SOFIA/upGREAT observations of the [C II] 158 µm line and IRAM 30 m observations of the 13CO (J = 2−1) line (the complete map is presented here for the first time). We observe small differences in peak velocities between the different tracers, which cannot always be attributed to geometry but potentially to shear motions. Using the far-infrared [C II] and [13C II] intensities with the carbon RRL intensities, we can infer physical conditions (electron temperature Te and electron density ne, converted to hydrogen nuclei density nH by dividing by the carbon gas-phase abundance 𝒜c ≃ 1.4 × 10−4) in the PDR gas using nonlocal thermal equilibrium excitation models. For positions in OMC1, we infer ne ≃ 20–40 cm−3 and Te ≃ 210–240 K. On the border between OMC1 and M43, we observe two gas components with ne ≃ 2 cm−3 and ne ≃ 8 cm−3, and Te ≃ 100 K and Te ≃ 150 K. In M43, we infer ne ≃ 2–3 cm−3 and Te ≃ 140 K. The Extended Orion Nebula southeast of OMC1 is characterized by ne ≃ 2 cm−3 and Te ≃ 180 K, while OMC3 has ne ≃ 1 cm−3 and Te ≃ 130 K. Our observations are sensitive enough to detect faint lines toward two positions in OMC1, in the BN/KL PDR and the PDR close to the Trapezium stars, that may be attributed to RRLs of C+ or O+. In general, the RRL line widths of both the ionized and neutral gas, as well as the [C II] and 13CO line widths, are broader than thermal, indicating significant turbulence in the interstellar medium, which transitions from super-Alfvénic and subsonic in the ionized gas to sub-Alfvénic and supersonic in the molecular gas. At the scales probed by our observations, the turbulent pressure dominates the pressure balance in the neutral and molecular gas, while in the ionized gas the turbulent pressure is much smaller than the thermal pressure.

Cholinergic nucleus degeneration and its association with gait impairment in Parkinson’s disease

BackgroundThe contribution of cholinergic degeneration to gait disturbance in Parkinson’s disease (PD) is increasingly recognized, yet its relationship with dopaminergic-resistant gait parameters has been poorly investigated. We investigated the association between comprehensive gait parameters and cholinergic nucleus degeneration in PD.MethodsThis cross-sectional study enrolled 84 PD patients and 69 controls. All subjects underwent brain structural magnetic resonance imaging to assess the gray matter density (GMD) and volume (GMV) of the cholinergic nuclei (Ch123/Ch4). Gait parameters under single-task (ST) and dual-task (DT) walking tests were acquired using sensor wearables in PD group. We compared cholinergic nucleus morphology and gait performance between groups and examined their association.ResultsPD patients exhibited significantly decreased GMD and GMV of the left Ch4 compared to controls after reaching HY stage > 2. Significant correlations were observed between multiple gait parameters and bilateral Ch123/Ch4. After multiple testing correction, the Ch123/Ch4 degeneration was significantly associated with shorter stride length, lower gait velocity, longer stance phase, smaller ankle toe-off and heel-strike angles under both ST and DT condition. For PD patients with HY stage 1–2, there were no significant degeneration of Ch123/4, and only right side Ch123/Ch4 were corrected with the gait parameters. However, as the disease progressed to HY stage > 2, bilateral Ch123/Ch4 nuclei showed correlations with gait performance, with more extensive significant correlations were observed in the right side.ConclusionsOur study demonstrated the progressive association between cholinergic nuclei degeneration and gait impairment across different stages of PD, and highlighting the potential lateralization of the cholinergic nuclei’s impact on gait impairment. These findings offer insights for the design and implementation of future clinical trials investigating cholinergic treatments as a promising approach to address gait impairments in PD.

Stabilizing Solution–Substrate Interaction of Perovskite Ink on PEDOT:PSS for Scalable Blade Coated Narrow Bandgap Perovskite Solar Modules by Gas Quenching

The development of scalable 1.25 eV mixed Pb–Sn perovskite solar modules by blade coating lags behind Pb‐based perovskites due to limited understanding of solution–substrate interaction of the perovskite ink on PEDOT:PSS and subsequent gas quenching. To address this challenge, the wet film deposition and quenching process to better understand narrow bandgap perovskite film formation on PEDOT:PSS are studied. It is found that the wetting of Pb–Sn perovskite ink on PEDOT:PSS is highly unstable over relevant coating time scales, causing the contact angles to decrease rapidly from 42° to 16° within seconds. This instability leads to localized irregularities in the wet film, resulting in uneven solvent extraction and inhomogeneous nuclei density. As a result, rough perovskite films with voids at the buried interface are obtained. To overcome this problem, a quasistatic wetting process by reducing the blade coating speed is developed, thereby stabilizing the wetting behavior of Pb–Sn perovskite precursor ink on PEDOT:PSS. This optimized process facilitates the deposition of high‐quality, void‐free Pb–Sn perovskite films with uniform thickness over 8 cm of coating length using moderate (1.4 bar) N2 quenching. 20% efficient narrow bandgap perovskite solar cells and minimodules with 15.8% active area efficiency on 15.9 cm2 are achieved.

Late gestation fetal hypothyroidism alters cell cycle regulation across multiple organ systems

BackgroundHypothyroidism is a common endocrine disruption observed in utero that adversely affects fetal growth and maturation leading to long-term impacts on health; however, the exact molecular mechanisms by which these deleterious effects occur are unknown. We hypothesize that fetal hypothyroidism during late gestation will disrupt cell cycle regulation in a tissue-specific manner. To evaluate this, eight pregnant gilts were dosed with either methimazole or an equivalent negative control during days 85–106 out of 114 days of gestation (n = 4/group). Following treatment, the gilts were humanely euthanized, and tissue samples of fetal heart, ileum, kidney, lung, liver, muscle, spleen, and thymus taken from two male and two female fetuses (n = 32) from each gilt.ResultsThe relative expression of three cell cycle promoters (CDK1, CDK2, and CDK4), and one cell cycle inhibitor (CDKN1A) was compared in each tissue to determine the effect of hypothyroidism on the developing fetus. All of the eight tissues examined experienced at least one significant up- or downregulation in the expression of the aforementioned genes as a result of treatment with methimazole. Substantial changes were observed in the liver and muscle, with the latter experiencing significant downregulations of CDK1, CDK2, and CDK4 as a result of treatment. In addition, all tissues were examined for changes in protein content, which further elucidated the impact of hypothyroidism on the fetal liver by the observation of a marked increase in protein content in the methimazole-treated group. Finally, the heart and liver were histologically examined for evidence of cellular hyperplasia and hypertrophy by measuring average nuclei density and size in each tissue, with the results showing a significant decrease in average nuclei size in the liver of hypothyroid fetuses.ConclusionsCollectively, these findings indicate the occurrence of organ-specific disruptions in cell cycle progression as a result of in utero hypothyroidism, which may explain the long term and widespread effects of hypothyroidism on fetal development.

Predictive model based on multiple immunofluorescence quantitative analysis for pathological complete response to neoadjuvant immunochemotherapy in lung squamous cell carcinoma.

This study aims to establish a prediction model for neoadjuvant immunochemotherapy (NICT) in lung squamous cell carcinoma to guide clinical treatment. This retrospective study included 50 patients diagnosed with lung squamous cell carcinoma who received NICT. The patients were divided into the pathological complete response (PCR) group and the non-PCR group. HE staining and multiple immunofluorescence (mIF) techniques were utilized to analyze the differences in the immune microenvironment between these groups. LASSO regression and optimal subset regression were employed to identify the most significant variables and construct a prediction model. The PCR group showed higher densities of lymphocyte nuclei and karyorrhexis based on HE staining. Furthermore, based on mIF analysis, the PCR group showed higher cell densities of CD8+, PD-L1+, and CD8+PD-L1+ in the tumor region, while showing lower cell densities of CD3+Foxp3+, Foxp3+, and CD163+. Logistic univariate analysis revealed CD8+PD-L1+, PD-L1+, CD8+, CD4+LAG-3+, lymphocyte nuclei, and karyorrhexis as significant factors influencing PCR. By using diverse screening methods, the three most relevant variables (CD8+, PD-L1+, and CD8+PD-L1+ in the tumor region) were selected to establish the prediction model. The model exhibited excellent performance in both the training set (AUC=0.965) and the validation set (AUC=0.786). In the validation set, In comparison to the conventional TPS scoring criteria, the model attained superior accuracy (0.85), specificity(0.67), and sensitivity (0.92). NICT treatment might induce anti-tumor effects by enriching immune cells and reactivating exhausted T cells. CD8+, PD-L1+, and CD8+PD-L1+ cell abundances within the tumor region have been closely associated with therapeutic efficacy. Incorporating these three variables into a predictive model allows accurate forecasting of treatment outcomes and provides a reliable basis for selecting NICT treatment strategies.

Intraperitoneal injection of mesenchymal stem cells-conditioned media (MSCS-CM) treated monocyte can potentially alleviate motor defects in experimental autoimmune encephalomyelitis female mice; An original experimental study

IntroductionMultiple sclerosis (MS), as a destructive pathology of myelin in central nervous system (CNS), causes physical and mental complications. Experimental autoimmune encephalomyelitis (EAE) is laboratory model of MS widely used for CNS-associated inflammatory researches. Cell therapy using macrophage M2 (MPM2) is a cell type with anti-inflammatory characteristics for all inflammatory-based neuropathies. This experimental study investigated the probable therapeutic anti-inflammatory effects of intraperitoneal (IP) injection of MPM2 on alleviation of motor defect in EAE-affected animals. Materials and methods24 C57/BL6 female mice were divided into four groups of EAE, EAE + Dexa, EAE + PBS, and EAE + MP2. EAE was induced through deep cervical injection of spinal homogenate of guinea pigs. MPM2 cells were harvested from bone marrow and injected (106cells/ml) in three days of 10, 13 and 16 post-immunizations (p.i). Clinical score (CS), anti-inflammatory cytokines (IL-4, IL-10), pro-inflammatory gene expression (TNF-α, IL-1β) and histopathological investigations (HE, Nissl and Luxol Fast Blue) were considered. Data were analyzed using SPSS software (v.19) and p < 0.05 was considered significant level. ResultsDuring EAE induction, the mean animal weight was decreased (p < 0.05); besides, following MPM2 injection, the weight gain was applied (p < 0.05) in EAE + MPM2 groups than control. Increased (p < 0.05) levels of CS was found during EAE induction in days 17–28 in EAE animals; besides, CS was decreased (p < 0.05) in EAE + MPM2 group than EAE animals. Also, in days 25–28 of experiment, the CS was decreased (p < 0.05) in EAE + MPM2 than EAE + Dexa. Histopathological assessments revealed low density of cell nuclei in corpus callosum, microscopically. LFB staining also showed considerable decrease in white matter density of corpus callosum in EAE group. Acceleration of white matter density was found in EAE + MPM2 group following cell therapy procedure. Genes expression of TNF-α, IL-1β along with IL-4 and IL-10 were decreased (p < 0.05) in EAE + MPM2 group. ConclusionIP injection of MPM2 to EAE-affected female mice can potentially reduce the CNS inflammation, neuronal death and myelin destruction. MPM2 cell therapy can improve animal motor defects.

SNCA and TPPP transcripts increase in oligodendroglial cytoplasmic inclusions in multiple system atrophy

Multiple system atrophy (MSA) is characterized by glial cytoplasmic inclusions (GCIs) containing aggregated α-synuclein (α-syn) in oligodendrocytes. The origin of α-syn accumulation in GCIs is unclear, in particular whether abnormal α-syn aggregates result from the abnormal elevation of endogenous α-syn expression in MSA or ingested from the neuronal source. Tubulin polymerization promoting protein (TPPP) has been reported to play a crucial role in developing GCI pathology. Here, the total cell body, nucleus, and cytoplasmic area density of SNCA and TPPP transcripts in neurons and oligodendrocytes with and without various α-syn pathologies in the pontine base in autopsy cases of MSA (n = 4) and controls (n = 2) were evaluated using RNAscope with immunofluorescence. Single-nucleus RNA-sequencing data for TPPP was evaluated using control frontal cortex (n = 3). SNCA and TPPP transcripts were present in the nucleus and cytoplasm of oligodendrocytes in both controls and diseased, with higher area density in GCIs and glial nuclear inclusions in MSA. Area densities of SNCA and TPPP transcripts were lower in neurons showing cytoplasmic inclusions in MSA. Indeed, TPPP transcripts were unexpectedly found in neurons, while the anti-TPPP antibody failed to detect immunoreactivity. Single-nucleus RNA-sequencing revealed significant TPPP transcript expression predominantly in oligodendrocytes, but also in excitatory and inhibitory neurons. This study addressed the unclear origin of accumulated α-syn in GCIs, proposing that the elevation of SNCA transcripts may supply templates for misfolded α-syn. In addition, the parallel behavior of TPPP and SNCA transcripts in GCI development highlights their potential synergistic contribution to inclusion formation. In conclusion, this study advances our understanding of MSA pathogenesis, offers insights into the dynamics of SNCA and TPPP transcripts in inclusion formation, and proposes regulating their transcripts for future molecular therapy to MSA.