Local Response Research Articles

Study of defect mode characteristics in acoustic metamaterials

The development of novel material architectures incorporating unconventional geometric designs (e.g., microstructural instabilities, multi-length scale geometries), or adaptive constituent elements (e.g., piezo electrics) has created a powerful tool to design metamaterials for efficient dispersion manipulation and precise control of acoustic waves. Various aspects of the acoustic dispersion (e.g., wave speed, damping ratio, band gap position and widths) have been investigated with a primary focus on wave characteristics in the acoustic pass bands, promoting their utility in applications, e.g., wave guiding, energy harvesting. However, recent studies on topological waves, truncation and bandgap resonances have highlighted potential benefits of leveraging acoustic waves in the bandgap, e.g., signal propagation, passive flow control. Motivated by this, we explore the dispersion behavior of finite mass-spring-damper acoustic metamaterial models with material defects. The eigen analysis reveals a (defect) resonance in the acoustic band gap, producing a highly localized defect mode. The dependence of this resonance frequency, the degree of localization and phase response of the eigenmode, on the defect parameters are explored. Subsequently, the potential utility of these defect modes in flow control applications is also explored and presented.

Combination of intrahepatic TARE and extrahepatic TACE to treat HCC patients with extrahepatic artery supply: A case series

PurposeThe aim of this study was to report the safety and tumor response rate of combined transarterial radioembolization (TARE) through the intrahepatic arteries and transarterial chemoembolization (TACE) through the extrahepatic feeding arteries (EHFA) in patients with hepatocellular carcinoma (HCC). MethodsPatients with HCC, who had both intrahepatic and extrahepatic arterial supply visible on preinterventional multiphase CT and were treated between 2016 and 2021 with a combination of TACE and TARE on the same nodule, were retrospectively included. Epidemiological, clinical, biological, and radiological characteristics were recorded. Safety and tumor response were assessed at 6 months. ResultsNine patients (8 men, median age 62 years [IQR: 54–72 years]) were included. Seven patients had previous treatments on the target nodule (TARE: 5; TACE: 2). The median longest axis (LA) of the lesion was 70 mm (IQR: 60–79 mm). Three patients had portal vein invasion (VP3). The EHFA originated from the right diaphragmatic artery (n = 6), the right adrenal artery (n = 2), and the left gastric artery (n = 1). The LA of the tumor portion treated with TACE was 47 mm (range: 35–64 mm). The ratio between the LA of the entire lesion and the LA treated with TACE was 1.44 (range: 1.27–1.7). One major complication occurred: acute on chronic liver failure. Median follow-up was 23 months (range: 16–29 months). Seven patients underwent further treatment: on the same lesion (n = 2), on newly appeared nodules (n = 2), and systemic treatment (n = 3). At 6-month follow-up, seven patients showed a local objective response. Time-to-progression was 13 (3.5–19) months. ConclusionThe combination of TARE and extrahepatic TACE for HCC with both intrahepatic and extrahepatic arterial supplies seems feasible and safe. Further studies are needed to validate the effectiveness of these preliminary results.

Multifunctional metasurface for ultrafast all-optical efficient modulation of terahertz wave

Metasurfaces have been widely used to terahertz (THz) modulators due to their unique electromagnetic (EM) modulation properties. However, to realize ultrafast and efficient control of the active metasurfaces remains a critical challenge. Herein, we first demonstrate a multifunctional metasurface modulator based on metal square rings, which have central rotational symmetry with local asymmetry. The former captures more EM energy to achieve strong enhancement of the local EM responses, and the latter generates high quality factor (Q-factor) Fano resonance. By scaling the unit structure, the resonant frequency shifts in an ultra-wideband range of ∼0.29-10 THz, which shows a linear relation between the Q-factor and the scaling factor, and an exponential variation between the full width at half maximum (FWHM) and the scaling factor. The results provide an effective approach to predict the frequency selection characteristics of the modulators in the THz regime. More importantly, by embedding the silicon into the specific position of the metasurface, external optical control results in the unit structure is constructed from meta-atom to molecularization model, the shifting of resonant frequency and the multi-level modulation of amplitude are realized, and the maximum modulation depth (MD) reaches ∼100 %. By systematically studying the dynamics of frequency and amplitude regulation, benefiting from the ultra-short relaxation time of the photo-carriers in silicon bridge, an ultrafast full recovery time of 2000 ps is achieved. Combined with the local field characteristics, the scaled unit structure achieves efficient modulation of the resonant frequency and amplitude under optical pumping, which provides a promising approach for the development of active metasurface modulator suitable for the whole THz band. This work demonstrates the viability of optical control molecularization of specific meta-atoms is applicable to the entire THz band, which has great potential use for future state-of-the-art THz modulators.

The impact of policy and policy communication on COVID-19 vaccination inequalities among Venezuelan refugees and migrants in Colombia: a comparative cross-sectional interrupted time-series analysis

IntroductionEquitable access to vaccines for migrants and refugees is necessary to ensure their right to health and to achieve public health goals of reducing vaccine-preventable illness. Public health policies require...

Magnetically driven capsules with multimodal response and multifunctionality for biomedical applications

Untethered capsules hold clinical potential for the diagnosis and treatment of gastrointestinal diseases. Although considerable progress has been achieved recently in this field, the constraints imposed by the narrow spatial structure of the capsule and complex gastrointestinal tract environment cause many open-ended problems, such as poor active motion and limited medical functions. In this work, we describe the development of small-scale magnetically driven capsules with a distinct magnetic soft valve made of dual-layer ferromagnetic soft composite films. A core technological advancement achieved is the flexible opening and closing of the magnetic soft valve by using the competitive interactions between magnetic gradient force and magnetic torque, laying the foundation for the functional integration of both drug release and sampling. Meanwhile, we propose a magnetic actuation strategy based on multi-frequency response control and demonstrate that it can achieve effective decoupled regulation of the capsule’s global motion and local responses. Finally, through a comprehensive approach encompassing ideal models, animal ex vivo models, and in vivo assessment, we demonstrate the versatility of the developed magnetic capsules and their multiple potential applications in the biomedical field, such as targeted drug delivery and sampling, selective dual-drug release, and light/thermal-assisted therapy.

Involvement of the Gut Microbiome in the Local and Systemic Immune Response to Pancreatic Ductal Adenocarcinoma.

The systemic and local immunosuppression exhibited by pancreatic ductal adenocarcinoma (PDAC) contributes significantly to its aggressive nature. There is a need for a greater understanding of the mechanisms behind this profound immune evasion, which makes it one of the most challenging malignancies to treat and thus one of the leading causes of cancer death worldwide. The gut microbiome is now thought to be the largest immune organ in the body and has been shown to play an important role in multiple immune-mediated diseases. By summarizing the current literature, this review examines the mechanisms by which the gut microbiome may modulate the immune response to PDAC. Evidence suggests that the gut microbiome can alter immune cell populations both in the peripheral blood and within the tumour itself in PDAC patients. In addition, evidence suggests that the gut microbiome influences the composition of the PDAC tumour microbiome, which exerts a local effect on PDAC tumour immune infiltration. Put together, this promotes the gut microbiome as a promising route for future therapies to improve immune responses in PDAC patients.

SDF-1 involvement in orthodontic tooth movement after tooth extraction

The stromal cell-derived factor 1 (SDF-1)/chemokine receptor type 4 (CXCR4) axis plays a key role in alveolar bone metabolism during orthodontic tooth movement (OTM). Herein, the effects of the SDF-1/CXCR4 axis on the regional acceleratory phenomenon (RAP) in OTM velocity and on changes in the surrounding periodontium after adjacent tooth extraction in rats were investigated. Six-week-old male Wistar/ST rats underwent left maxillary first molar (M1) extraction and mesial OTM of the left maxillary second molar (M2) with a 10-g force closed-coil spring. Phosphate-buffered saline, immunoglobulin G (IgG) isotype control antibody, or anti-SDF-1 neutralizing monoclonal antibody were injected at the M1 and M2 interproximal areas (10 μg/0.1 mL) for the first three days. Analyses were performed after 1, 3, and 7 days (n = 7). The results demonstrated a significant increase in SDF-1 expression from day 1, which was effectively blocked via anti-SDF-1 neutralizing monoclonal antibody injection. On day 3, the M2 OTM distance and the number of positively stained osteoclasts significantly reduced alongside a reduction in inflammatory markers in the experimental group. Our results demonstrated that serial local injection of the anti-SDF-1 neutralizing monoclonal antibody reduces M2 OTM, osteoclast accumulation, and localized inflammatory responses in an OTM model with tooth extraction-induced RAP.

The effect of combining an inhaled corticosteroid and a long-acting muscarinic antagonist on human airway epithelial cells in vitro

BackgroundAirway epithelial cells (AECs) are a major component of local airway immune responses. Direct effects of type 2 cytokines on AECs are implicated in type 2 asthma, which is driven by epithelial-derived cytokines and leads to airway obstruction. However, evidence suggests that restoring epithelial health may attenuate asthmatic features.MethodsWe investigated the effects of passive sensitisation on IL-5, NF-κB, HDAC-2, ACh, and ChAT in human bronchial epithelial cells (HBEpCs) and the effects of fluticasone furoate (FF) and umeclidinium (UME) alone and in combination on these responses.ResultsIL-5 and NF-κB levels were increased, and that of HDAC-2 reduced in sensitised HEBpCs. Pretreatment with FF reversed the effects of passive sensitisation by concentration-dependent reduction of IL-5, resulting in decreased NF-κB levels and restored HDAC-2 activity. Addition of UME enhanced these effects. Sensitized HEBpCs also exhibited higher ACh and ChAT levels. Pretreatment with UME significantly reduced ACh levels, and addition of FF caused a further small reduction.ConclusionThis study confirmed that passive sensitisation of AECs results in an inflammatory response with increased levels of IL-5 and NF-κB, reduced levels of HDAC-2, and higher levels of ACh and ChAT compared to normal cells. Combining FF and UME was found to be more effective in reducing IL-5, NF-κB, and ACh and restoring HDAC-2 compared to the individual components. This finding supports adding a LAMA to established ICS/LABA treatment in asthma and suggests the possibility of using an ICS/LAMA combination when needed.

Coordinated inflammatory responses dictate Marburg virus control by reservoir bats

Bats are increasingly recognized as reservoirs of emerging zoonotic pathogens. Egyptian rousette bats (ERBs) are the known reservoir of Marburg virus (MARV), a filovirus that causes deadly Marburg virus disease (MVD) in humans. However, ERBs harbor MARV asymptomatically, likely due to a coadapted and specific host immunity-pathogen relationship. Recently, we measured transcriptional responses in MARV-infected ERB whole tissues, showing that these bats possess a disease tolerant strategy that limits pro-inflammatory gene induction, presumably averting MVD-linked immunopathology. However, the host resistant strategy by which ERBs actively limit MARV burden remains elusive, which we hypothesize requires localized inflammatory responses unresolvable at bulk-tissue scale. Here, we use dexamethasone to attenuate ERB pro-inflammatory responses and assess MARV replication, shedding and disease. We show that MARV-infected ERBs naturally mount coordinated pro-inflammatory responses at liver foci of infection, comprised of recruited mononuclear phagocytes and T cells, the latter of which proliferate with likely MARV-specificity. When pro-inflammatory responses are diminished, ERBs display heightened MARV replication, oral/rectal shedding and severe MVD-like liver pathology, demonstrating that ERBs balance immunoprotective tolerance with discreet MARV-resistant pro-inflammatory responses. These data further suggest that natural ERB immunomodulatory stressors like food scarcity and habitat disruption may potentiate viral shedding, transmission and therefore outbreak risk.

Identifying Spatial Determinants of Rice Yields in Main Producing Areas of China Using Geospatial Machine Learning

Rice yield is essential to global food security under increasingly frequent and severe climate change events. Spatial analysis of rice yields becomes more critical for regional action to ensure yields and reduce climate impacts. However, the understanding of the spatially varied geographical, climate, soil, and environmental factors of rice yields needs to be improved, leading to potentially biased local rice yield prediction and responses to climate change. This study develops a spatial machine learning-based approach that integrates machine learning and spatial stratified heterogeneity models to identify the determinants and spatial interactions of rice yields in the main rice-producing areas of China, the world’s largest rice-producing nation. A series of satellite remote sensing-derived variables are collected to characterize varied geographical, climate, soil, and environmental conditions and explain the spatial disparities of rice yields. The first step is to explore the spatial clustering patterns of the rice yield distributions using spatially global and local autocorrelation models. Next, a Geographically Optimal Zones-based Heterogeneity (GOZH) model, which integrates spatial stratified heterogeneity models and machine learning, is employed to explore the power of determinants (PD) of individual spatial variables in influencing the spatial disparities of rice yields. Third, geographically optimal zones are identified with the machine learning-derived optimal spatial overlay of multiple geographical variables. Finally, the overall PD of various variables affecting rice yield distributions is calculated using the multiple variables-determined geographically optimal zones and the GOZH model. The comparison between the developed spatial machine learning-based approach and previous related models demonstrates that the GOZH model is an effective and robust approach for identifying the spatial determinants and their spatial interactions with rice yields. The identified spatial determinants and their interactions are essential for enhancing regional agricultural management practices and optimizing resource allocation within diverse main rice-producing regions. The comprehensive understanding of the spatial determinants and heterogeneity of rice yields of this study has a broad impact on agricultural strategies and food security.

Effect of high-frequency (5Hz) rTMS stimulating left DLPFC combined with galantamine on cognitive impairment after ischemic stroke and serum homocysteine and neuron-specific enolase.

To investigate the efficacy of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) combined with galantamine in patients with cognitive impairment after stroke and its effect on serum homocysteine (Hcy) and neuron-specific enolase (NSE) levels. A total of 90 patients with cognitive impairment after the first ischemic stroke were enrolled. They were randomly divided into rTMS+ cognitive rehabilitation group, Galantamine + cognitive rehabilitation group, and rTMS+ Galantamine + cognitive rehabilitation group. All groups received routine medical treatment and limb rehabilitation treatment. The rTMS stimulation site was the left dorsolateral prefrontal cortex (left DLPFC), the magnetic stimulation frequency was 5 Hz, the magnetic stimulation intensity was 80% of the motor threshold level, and 3,000 pulses were given every day. The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Fugl-Meyer scale, and modified Barthel index, as well as rehabilitation scale and serum NSE and Hcy were evaluated before and after treatment (after 4 weeks). After 4 weeks of treatment, the scores of MMSE, MoCa scale, Fugl-Meyer scale, and modified Barthel index in the three groups were significantly higher than those before treatment (all p < 0.05), while the serum NSE and Hcy levels of the three groups were decreased. rTMS+ Galantamine + cognitive rehabilitation group had higher scale scores, and the difference between the three groups was statistically significant compared with the other two groups (all p < 0.05). Cognitive rehabilitation combined with HF-rTMS and galantamine could improve the cognitive function of patients to the greatest extent, promote the recovery of physical activity, improve the self-care ability of daily life, and effectively reduce the serum HCY and NSE levels in patients with cognitive impairment after stroke. No randomized controlled trials of similar combination treatments have been reported. The better therapeutic effect may be related to the fact that galantamine combined with repetitive transcranial magnetism can activate the brain cholinergic system more extensively, promote brain neural remodeling through long-term potentiation and inhibit local neuroinflammatory responses in brain injury.

Paraspinal muscle oxygenation and mechanical efficiency are reduced in individuals with chronic low back pain

This study aimed to compare the systemic and local metabolic responses during a 5-min trunk extension exercise in individuals with chronic low back pain (CLBP) and in healthy individuals. Thirteen active participants with CLBP paired with 13 healthy participants performed a standardised 5-min trunk extension exercise on an isokinetic dynamometer set in continuous passive motion mode. During exercise, we used near-infrared spectroscopy to measure tissue oxygenation (TOI) and total haemoglobin-myoglobin (THb). We used a gas exchange analyser to measure breath-by-breath oxygen consumption (V̇O2) and carbon dioxide produced (V̇CO2). We also calculated mechanical efficiency. We assessed the intensity of low back pain sensation before and after exercise by using a visual analogue scale. In participants with CLBP, low back pain increased following exercise (+ 1.5 units; p < 0.001) and THb decreased during exercise (− 4.0 units; p = 0.043). Paraspinal muscle oxygenation (65.0 and 71.0%, respectively; p = 0.009) and mechanical efficiency (4.7 and 5.3%, respectively; p = 0.034) were both lower in participants with CLBP compared with healthy participants. The increase in pain sensation was related to the decrease in tissue oxygenation (R2 = − 0.420; p = 0.036). Decreases in total haemoglobin-myoglobin and mechanical efficiency could involve fatigability in exercise-soliciting paraspinal muscles and, therefore, exacerbate inabilities in daily life. Given the positive correlation between tissue oxygenation and exercise-induced pain exacerbation, muscle oxygenation may be related to persisting and crippling low back pain.

Gonadal androgens are associated with decreased type I interferon production by plasmacytoid dendritic cells and increased IgG titres to BNT162b2 following co-vaccination with live attenuated influenza vaccine in adolescents.

mRNA vaccine technologies introduced following the SARS-CoV-2 pandemic have highlighted the need to better understand the interaction of adjuvants and the early innate immune response. Type I interferon (IFN-I) is an integral part of this early innate response that primes several components of the adaptive immune response. Women are widely reported to respond better than men to tri- and quadrivalent influenza vaccines. Plasmacytoid dendritic cells (pDCs) are the primary cell type responsible for IFN-I production, and female pDCs produce more IFN-I than male pDCs since the upstream pattern recognition receptor Toll-like receptor 7 (TLR7) is encoded by X chromosome and is biallelically expressed by up to 30% of female immune cells. Additionally, the TLR7 promoter contains several putative androgen response elements, and androgens have been reported to suppress pDC IFN-I in vitro. Unexpectedly, therefore, we recently observed that male adolescents mount stronger antibody responses to the Pfizer BNT162b2 mRNA vaccine than female adolescents after controlling for natural SARS-CoV-2 infection. We here examined pDC behaviour in this same cohort to determine the impact of IFN-I on anti-spike and anti-receptor-binding domain IgG titres to BNT162b2. Through flow cytometry and least absolute shrinkage and selection operator (LASSO) modelling, we determined that serum-free testosterone was associated with reduced pDC IFN-I, but contrary to the well-described immunosuppressive role for androgens, the most bioactive androgen dihydrotestosterone was associated with increased IgG titres to BNT162b2. Also unexpectedly, we observed that co-vaccination with live attenuated influenza vaccine boosted the magnitude of IgG responses to BNT162b2. Together, these data support a model where systemic IFN-I increases vaccine-mediated immune responses, yet for vaccines with intracellular stages, modulation of the local IFN-I response may alter antigen longevity and consequently improve vaccine-driven immunity.

STING inhibition alleviates bone resorption in apical periodontitis.

The goal of this study was to investigate the potential effects of an immunotherapeutic drug targeting STING to suppress the overreactive innate immune response and relieve the bone defect in apical periodontitis. We established an apical periodontitis mouse model in Sting-/- and WT mice in vivo. The progression of apical periodontitis was analysed by micro-CT analysis and H&E staining. The expression level and localization of STING in F4/80+ cells were identified by IHC and immunofluorescence staining. RANKL in periapical tissues was tested by IHC staining. TRAP staining was used to detect osteoclasts. To clarify the effect of STING inhibitor C-176 as an immunotherapeutic drug, mice with apical periodontitis were treated with C-176 and the bone loss was identified by H&E, TRAP, RANKL staining and micro-CT. Bone marrow-derived macrophages (BMMs) were isolated from Sting-/- and WT mice and induced to osteoclasts in a lipopolysaccharide (LPS)-induced inflammatory environment in vitro. Moreover, WT BMMs were treated with C-176 to determine the effect on osteoclast differentiation by TRAP staining. The expression levels of osteoclast-related genes were tested using qRT-PCR. Compared to WT mice, the bone resorption and inflammatory cell infiltration were reduced in exposed Sting-/- mice. In the exposed WT group, STING was activated mainly in F4/80+ macrophages. Histological staining revealed the less osteoclasts and lower expression of osteoclast-related factor RANKL in Sting-/- mice. The treatment of the STING inhibitor C-176 in an apical periodontitis mice model alleviated inflammation progression and bone loss, similar to the effect observed in Sting-/- mice. Expression of RANKL and osteoclast number in periapical tissues were also decreased after C-176 administration. In vitro, TRAP staining showed fewer positive cells and qRT-PCR reflected decreased expression of osteoclastic marker, Src and Acp5 were detected during osteoclastic differentiation in Sting-/- and C-176 treated BMMs. STING was activated and was proven to be a positive factor in bone loss and osteoclastogenesis in apical periodontitis. The STING inhibitor C-176 administration could alleviate the bone loss via modulating local immune response, which provided immunotherapy to the treatment of apical periodontitis.

Prebiotic effect of galacto-N-biose on the intestinal lactic acid bacteria as enhancer of acetate production and hypothetical colonization.

Specific members of lactic acid bacteria, which are commonly used as probiotics, possess therapeutic properties that are vital for human health enhancement by producing immunomodulatory metabolites such as exopolysaccharides, short-chain fatty acids, and bacteriocins. The long residence time of probiotic lactic acid bacteria in the GI tract prolongs their beneficial health effects. Moreover, the colonization property is also desirable for the application of probiotics in mucosal vaccination to provoke a local immune response. In this study, we found that GNB could enhance the beneficial properties of intestinal lactic acid bacteria that inhabit the human GI tract, stimulating acetate production and promoting intestinal colonization. Our findings provide a rationale for the addition of GNB to lactic acid bacteria-based functional foods. This has also led to the development of therapeutics supported by more rational prebiotic and probiotic selection, leading to an improved healthy lifestyle for humans.

Uncovering the Bronchoalveolar Single-Cell Landscape of Patients With Pulmonary Tuberculosis With Human Immunodeficiency Virus Type 1 Coinfection.

Coinfection of human immunodeficiency virus type 1 (HIV-1) is the most significant risk factor for tuberculosis (TB). The immune responses of the lung are essential to restrict the growth of Mycobacterium tuberculosis and avoid the emergence of the disease. Nevertheless, there is still limited knowledge about the local immune response in people with HIV-1-TB coinfection. We employed single-cell RNA sequencing (scRNA-seq) on bronchoalveolar lavage fluid from 9 individuals with HIV-1-TB coinfection and 10 with pulmonary TB. A total of 19 058 cells were grouped into 4 major cell types: myeloid cells, T/natural killer (NK) cells, B cells, and epithelial cells. The myeloid cells and T/NK cells were further divided into 10 and 11 subsets, respectively. The proportions of dendritic cell subsets, CD4+ T cells, and NK cells were lower in the HIV-1-TB coinfection group compared to the TB group, while the frequency of CD8+ T cells was higher. Additionally, we identified numerous differentially expressed genes between the CD4+ and CD8+ T-cell subsets between the 2 groups. HIV-1 infection not only affects the abundance of immune cells in the lungs but also alters their functions in patients with pulmonary TB.

Gender disparities in thermal responses under vertical air temperature differences

The effects of vertical temperature differences (VTD) on human thermal comfort have attracted growing attention from researchers when utilizing split air conditioners for winter heating. This study underscores the need to investigate the influences of gender disparities in the context of significant vertical temperature variations, a critical aspect that has not yet been comprehensively explored. Twenty gender-balanced subjects were exposed to a variety of stratified thermal environments created by a split air-conditioner. Their overall and local perceptual and physiological responses were measured at various operative temperatures and VTD. Results show that females have lower thermal sensation vote (TSV) and mean skin temperature under the same environments compared to males. Neutral operative temperatures of females and males are 23.7 ˚C and 20.8 ˚C, respectively. On the cold side, lower leg and foot thermal sensations are dominant whereas chest and back are dominant on the warm side. When females rated “slightly warm” (TSV equaled 1) or “warm” (TSV equaled 2), or males rated “slightly cool” (TSV equaled −1), increased VTD can lower thermal acceptability. The research findings have significant implications for the understanding of gender requirements of stratified heating environments and for maximizing the thermal comfort of the two genders.

A comprehensive exploration of diverse skin cell types in the limb of the desert tortoise (Testudo graeca) through light, transmission, scanning electron microscopy, and immunofluorescence techniques

The Greek tortoise, inhabiting harsh desert environments, provides a compelling case for investigating skin adaptations to extreme conditions. We have utilized light microscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and immunofluorescence analysis to describe the structure of the arid-adapted limb skin in the Greek tortoise. Our aim was to identify the cell types that reflect the skin adaptation of this tortoise to arid conditions. Utilizing seven antibodies, we localized and elucidated the functions of various skin cells, shedding light on how the tortoise adapts to adverse environmental conditions. Our findings unveiled numerous scales on the limbs, varying in size and color, acting as protective armor against abrasions, bites, and other potential threats in their rocky habitats. The epidermis comprises four layers: stratum basalis, stratum spinosum, peri-corneous layer, and stratum corneum. Cytokeratin 14 (CK14) was explicitly detected in the basal layer of the epidermis, suggesting a role in maintaining epidermal integrity and cellular function. Langerhans cells were observed between epidermal cells filled with ribosomes and Birbeck granules. Numerous dendritic-shaped Langerhans cells revealed through E-Cadherin signify strong immunity in tortoises' skin. Melanophores were identified using the Melan-A antibody, labeling the cytoplasm, and the SOX10 antibody, labeling the nucleus, providing comprehensive insights into melanophores morphology and distribution. Two types of melanophores were found: dendritic below the stratum basalis of the epidermis and clustered oval melanophores in the deep dermal layer. Varied melanophores distribution resulted in a spotted skin pattern, potentially offering adaptive camouflage and protection against environmental challenges. Numerous myofibroblasts were discerned through alpha-smooth actin (α-SMA) expression, indicating that the Greek tortoise's skin possesses a robust tissue repair and remodeling capacity. B-cell lymphocytes detected via CD20 immunostaining exhibited sporadic distribution in the dermis, concentrating in lymphoid aggregates and around vessels, implying potential roles in local immune responses and inflammation modulation. Employing Tom20 to identify skin cells with abundant mitochondria revealed a notable presence in melanophores and the basal layer of the epidermis, suggesting high metabolic activity in these cell types and potentially influencing cellular functions. These findings contribute to our comprehension of tortoise skin anatomy and physiology, offering insights into the remarkable adaptations of this species finely tuned to their specific environmental habitats.

Representative bureaucracy and COVID‐19 among local emergency response professionals

AbstractThis article considers the opinions of local emergency management professionals with regard to the response of the US federal government to the COVID‐19 pandemic. The responses to a survey from May/June 2020 demonstrate that these feelings, ranging from highly successful to extremely poor, are reflective of the culture at large in the nation. The study will examine whether the feelings expressed by local officials are reflective of prevailing political leanings of their constituency, measured as the presidential voting habits from 2000 to 2020 in the respondent's jurisdiction. This will extend Hildebrand's (2020) testing which linked the emergency management field to the theory of “representative bureaucracy.” This theory surmises that government actors will be reflective of their body politic in their behavior and attitudes toward federal initiatives. The findings suggest that those who represent “Strong Republican” jurisdictions have greater odds in rating the federal response as being effective, and that those from “Strong Democrat” locations will have greater odds in rating the federal response as not effective at all. Statistical testing also suggests that as the population of the jurisdiction increases, the less likely the respondent was to consider the federal response to COVID‐19 effective.

Dual Role of Alchemilla vulgaris L. Extract in Breast Cancer Regression: Reestablishment of Effective Immune Response.

Ethnomedicinal records have long mentioned the historical usage of Alchemilla vulgaris L. in folk medicine, particularly for the treatment of gynecological issues. Building on this ethnomedicinal knowledge regarding female illnesses, the aim of this research was to evaluate the impact of ethanolic extract of A. vulgaris on mouse breast cancer cells (4T1) in vitro and in vivo, in addition to its effect on the immune compartment in the tumor microenvironment. Behind viability decrease of 4T1 cells induced by treatment with A. vulgaris extract was strong inhibition of cell proliferation accompanied by caspase-dependent apoptosis and autophagic cell death. Observed changes in 4T1 cell culture after treatment were well orchestrated and led to a reduction in metastatic potential through weakened adhesion, invasion, migration, and colony-forming abilities in vitro. Enhanced intracellular production of reactive oxygen and nitrogen species promoted by the treatment might interfere with all the observed effects. Apart from the direct effect on tumor cells, the A. vulgaris extract significantly reduced tumor growth in the solid orthotropic mammary carcinoma model through restitution of efficient local and systemic immune response reflected in enhanced antigen-presenting potential of dendritic cells (DCs) as well as the extent and activity of effector T cells.