Search Results (664)

Introduction: Actinic cheilitis (AC) is a common precancerous condition affecting the lips, primarily caused by prolonged ultraviolet radiation exposure. Various treatment options are available. However, the optimal treatment approach remains a subject of debate. Objective: To summarize and compare practice-relevant interventions for AC. Materials and Methods: A pre-defined protocol was registered in PROSPERO (CRD42021225182). Systematic searches in Medline, Embase, and Central, along with manual trial register searches, identified studies reporting participant clearance rates (PCR) or recurrence rates (PRR). Quality assessment for randomized controlled trials (RCTs) was conducted using the Cochrane Risk of Bias tool 2. Uncontrolled studies were evaluated using the tool developed by the National Heart, Lung, and Blood Institute. The generalized linear mixed model was used to pool proportions for uncontrolled studies. A pairwise meta-analysis for RCTs was applied, using the odds ratio (OR) as the effect estimate and the GRADE approach to evaluate the quality of the evidence. Adverse events were analyzed qualitatively. Results: A comprehensive inclusion of 36 studies facilitated an evaluation of 614 participants for PCR, and 430 patients for PRR. Diclofenac showed the lowest PCR (0.53, 95% confidence interval (CI) [0.41; 0.66]), while CO₂ laser showed the highest PCR (0.97, 95% CI [0.90; 0.99]). For PRR, Er:YAG laser showed the highest rates (0.14, 95% CI [0.08; 0.21]), and imiquimod the lowest (0.00, 95% CI [0.00; 0.06]). In a pairwise meta-analysis, the OR indicated a lower recurrence rate for Er:YAG ablative fractional laser (AFL)-primed methyl-aminolevulinate photodynamic therapy (MAL-PDT) (Er:YAG AFL-PDT) compared to methyl-aminolevulinate photodynamic therapy (MAL-PDT) alone (OR = 0.22, 95% CI [0.06; 0.82]). The CO₂ laser showed fewer local side effects than the Er:YAG laser, while PDTs caused more skin reactions. Due to qualitative data, comparability was limited, highlighting the need for individualized treatment. Conclusions: This study provides a complete and up-to-date evidence synthesis of practice-relevant interventions for AC, identifying the CO₂ laser as the most effective treatment and regarding PCR and imiquimod as most effective concerning PRR. Full article

Lysosomal storage disorders (LSDs) are inherited metabolic conditions characterized by lysosomal enzyme deficiencies leading to substrate accumulation. As genetic diseases, LSDs can be treated with gene therapies (GT), including the CRISPR/Cas systems. The CRISPR/Cas systems enable precise and programmable genome editing, leading to targeted modifications at specific genomic loci. While the classical CRISPR/Cas9 system has been extensively used to generate LSD disease models and correct disease-associated genetic alterations through homologous recombination (HR), recently described Cas proteins as well as CRISPR/Cas9-derived strategies such as base editing, prime editing, and homology-independent targeted integration (HITI) offer a novel way to develop innovative treatments for LSDs. The direct administration of the CRISPR/Cas9 system remains the primary strategy evaluated in several LSDs; nevertheless, the ex vivo CRISPR/Cas9-based approach has been recently explored, primarily in central nervous system-affecting LSDs. Ex vivo approaches involve genetically modifying, in theory, any patient cells in the laboratory and reintroducing them into the patient to provide a therapeutic effect. This manuscript reviews the molecular aspects of the CRISPR/Cas technology and its implementation in ex vivo strategies for LSDs while discussing novel approaches beyond the classical CRISPR/Cas9 system. Full article

Hypertension (HTN) is a major contributor to global morbidity and manifests in several variants, including salt-sensitive hypertension (SSHTN). SSHTN is defined by an increase in blood pressure (BP) in response to high dietary salt, and is associated with heightened cardiovascular risk, renal damage, and immune system activation. However, the role of granulocyte-macrophage colony-stimulating factor (GM-CSF) has not yet been explored in the context of SSHTN. Previously, we reported that GM-CSF is critical in priming bone marrow-derived (BMD)-macrophages (BMD-Macs) and BMD-dendritic cells (BMD-DCs) to become activated (CD38+) in response to salt. Further exploration revealed these cells differentiated into BMD-M1 Macs, CD38+ BMD-M1 Macs, BMD-type-2 conventional DCs (cDC2s), and CD38+ BMD-cDC2s. Additionally, BMD-monocytes (BMDMs) grown with GM-CSF and injected into SSHTN mice traffic to the kidneys and differentiate into Macs, CD38+ Macs, DCs, and CD38+ DCs. In the current study, we treated SSHTN mice with an anti-GM-CSF antibody (aGM) and found that preventive aGM treatment mitigated BP, prevented renal inflammation, and altered renal immune cells. In mice with established SSHTN, aGM treatment attenuated BP, reduced renal inflammation, and differentially affected renal immune cells. Adoptive transfer of aGM-treated BMDMs into SSHTN mice resulted in decreased renal trafficking. Additionally, aGM treatment of BMD-Macs, CD38+ BMD-M1 Macs, BMD-DCs, and CD38+ BMD-cDC2s led to decreased pro-inflammatory gene expression. These findings suggest that GM-CSF plays a role in SSHTN and may serve as a potential therapeutic target. Full article

The priming effect (PE), a microbially mediated process, critically regulates the balance between carbon sequestration and mineralization. This study used soils from different soil depths (0–20 cm, 20–40 cm, and 40–60 cm) under Picea schrenkiana forest in the Tianshan Mountains as the research object. An indoor incubation experiment was conducted by adding three concentrations (1% SOC, 2% SOC, and 3% SOC) of ¹³C-labelled glucose. We applied ¹³C isotope probe-phospholipid fatty acid (PLFA-SIP) technology to investigate the influence of readily labile organic carbon inputs on soil priming effect (PE), microbial community shifts at various depths, and the mechanisms underlying soil PE. The results indicated that the addition of ¹³C-labeled glucose accelerated the mineralization of soil organic carbon (SOC); CO₂ emissions were highest in the 0–20 cm soil layer and decreased trend with increasing soil depth, with significant differences observed across different soil layers (p < 0.05). Soil depth had a positive direct effect on the cumulative priming effect (CPE); however, it showed negative indirect effects through physico-chemical properties and microbial biomass. The CPE of the 0–20 cm soil layer was significantly positively correlated with ¹³C-Gram-positive bacteria, ¹³C-Gram-negative bacteria, and ¹³C-actinomycetes. The CPE of the 20–40 cm and 40–60 cm soil layers exhibited a significant positive correlation with cumulative mineralization (CM) and microbial biomass carbon (MBC). Glucose addition had the largest and most significant positive effect on the CPE. Glucose addition positively affected PLFAs and particularly microbial biomass. This study provides valuable insights into the dynamics of soil carbon pools at varying depths following glucose application, advancing the understanding of forest soil carbon sequestration. Full article

Surfactants are widely utilized in agriculture as emulsifying, dispersing, anti-foaming, and wetting agents. In these adjuvant roles, the inherent biological activity of the surfactant is secondary to the active ingredients. Here, the hydrophilic non-ionic surface-active tri-block copolymer Pluronic^® F68 is investigated for direct biological activity in wheat. F68 binds to and inserts into lipid membranes, which may benefit crops under abiotic stress. F68’s interactions with Triticum aestivum (var Juniper) seedlings and a seed-borne Bacillus spp. endophyte are presented. At concentrations below 10 g/L, F68-primed wheat seeds exhibited unchanged emergence. Root-applied fluorescein-F68 (fF68) was internalized in root epidermal cells and concentrated in highly mobile endosomes. The potential benefit of F68 in droughted wheat was examined and contrasted with wheat treated with the osmolyte, glycine betaine (GB). Photosystem II activity of droughted plants dropped significantly below non-droughted controls, and no clear benefit of F68 (or GB) during drought or rehydration was observed. However, F68-treated wheat exhibited increased transpiration values (for watered plants only) and enhanced shoot dry mass (for watered and droughted plants), not observed for GB-treated or untreated plants. The release of seed-borne bacterial endophytes into the spermosphere of germinating seeds was not affected by F68 (for F68-primed seeds as well as F68 applied to roots), and the planktonic growth of a purified Bacillus spp. seed endophyte was not reduced by F68 applied below the critical micelle concentration. These studies demonstrated that F68 entered wheat root cells, concentrated in endosomes involved in transport, significantly promoted shoot growth, and showed no adverse effects to plant-associated bacteria. Full article

Emotion recognition is an essential social ability that continues to develop across adolescence, a period of critical socio-emotional changes. In the present study, we examine how signals from different sensory modalities, specifically touch and facial expressions, are integrated into a holistic understanding of another’s feelings. Adolescents (n = 30) and young adults (n = 30) were presented with dynamic faces displaying either a positive (happy) or a negative (sad) expression. Crucially, facial expressions were anticipated by a tactile stimulation, either positive or negative. Across two experiments, we use different tactile primes, both in first-person experience (experiment 1) and in the vicarious experience of touch (experiment 2). We measured accuracy and reaction times to investigate whether tactile stimuli affect facial emotional processing. In both experiments, results indicate that adolescents were more sensitive than adults to the influence of tactile primes, suggesting that sensory cues modulate adolescents’ accuracy and velocity in evaluating emotion facial expression. The present findings offer valuable insights into how tactile experiences might shape and support emotional development and interpersonal social interactions. Full article

American citizens are significantly more likely to experience property crime victimization than violent crime victimization. During a staffing crisis, police prioritize limited resources in combating serious crime; however, property crimes remain impactful to the community. Therefore, agencies need to consider innovative ways to control property crime, such as “super-cocooning” strategies that alert residents to recent offenses. These strategies intend to empower the community to implement guardianship and crime prevention measures. For these strategies to be effective, they require public buy-in and support. The present study implements a preregistered information provision survey experiment (N = 2412), similar to the strategy of super-cocooning, to assess whether the public is more likely to support such strategies to combat property crime. Although the sample held overall high support of this strategy, exposure to a super-cocooning door hanger prime produced no significant changes in perceived effectiveness. However, there was observed racial heterogeneity in the treatments: non-White respondents assigned to the treatment relative to White respondents experienced significantly increased support of super-cocooning strategies. Implications for light-footprint crime control strategies, particularly during a staffing crisis, are discussed. Full article

Long- or post-COVID-19 syndrome, which is also designated by WHO as Post COVID-19 Condition (PCC), is characterized by the persistent symptoms that remain after recovery from SARS-CoV-2 infection. A worldwide consortium of Long COVID-19 Host Genetics Initiative (Long COVID-19 HGI) identified an SNP rs9367106 (G>C; chr6:41,515,652, GRCh38, p = 1.76 × 10⁻¹⁰, OR = 1.63, 95% CI: 1.40–1.89) that is associated with PCC. Unraveling the functional significance of this SNP is of prime importance to understanding the development of the PCC phenotypes and their therapy. Here, in Silico, I explored how the risk allele of this SNP alters the functional mechanisms and molecular pathways leading to the development of PCC phenotypes. Bioinformatic methods include physical interactions using HI-C and Chia-PET analysis, Transcription Factors (TFs) binding ability, RNA structure modeling, epigenetic, and pathway analysis. This SNP resides within two long RNA genes, LINC01276 and FOXP4-AS1, and is located at ~31 kb upstream of a transcription factor FOXP4. This DNA region, including this SNP, physically interacts with FOXP4-AS1 and FOXP4, implying that this regulatory SNP could alter the normal cellular function of FOXP4-AS1 and FOXP4. Furthermore, rs9367106 is in eQTL with the FOXP4 gene in lung tissue. rs9367106 carrying DNA sequences act as distant enhancers and bind with several transcription factors (TFs) including YY1, PPAR-α, IK-1, GR-α, and AP2αA. The G>C transition extensively modifies the RNA structure that may affect the TF bindings and enhancer functions to alter the interactions and functions of these RNA molecules. This SNP also includes an ALU/SINE sequence and alteration of which by the G>C transition may prevent IFIH1/MDA5 activation, leading to suppression of host innate immune responses. LINC01276 targets the MED20 gene that expresses mostly in brain tissues, associated with sleep disorders and basal ganglia abnormalities similar to some of the symptoms of PCC phenotypes. Taken together, G>C transition of rs9367601 may likely alter the function of all three genes to explain the molecular basis of developing the long-term symptomatic abnormalities in the lungs and brain observed after COVID-19 recovery. Full article

Since water contamination has become a serious concern, more effective environmental remediation methods are required. Chitosan (CHT)-based adsorbents have demonstrated high efficacy in removing pollutants due to their unique chemical and structural properties. However, their utilization remains limited by low environmental stability and the absence of effective adsorption sites. The functional moieties of CHT can be altered to improve its performance via graft modification and crosslinking. Compared to conventional hydrogel synthesis techniques, ionizing radiation-induced fabrication, using gamma or electron-beam irradiation, offers a promising platform for innovation across diverse fields. The prime focus of this review is on ionizing radiation developed CHT-based hydrogels to remove toxic heavy metals, dyes, organic contaminants, radionuclides, and humic substances. The fabrication strategy, adsorption mechanism, and factors affecting the adsorption capacity of CHT-based hydrogels are presented. This review aims to underscore the transformative potential of ionizing radiation-induced CHT hydrogels in environmental remediation by examining current research trends and identifying future prospects. Full article

Taken together, cardiovascular diseases (CVDs) have become one of the prime causes of the global disease burden. Aging is closely related to CVDs and is considered to be one of the crucial factors in the incidence of CVDs. In the process of aging, cellular senescence is an important cause of CVDs such as atherosclerosis and atrial fibrillation. The treatment for CVDs by targeting senescent cells has been carried out in cellular models, animal experiments, and anti-aging clinical trials. Chemical approaches to regulate the fate of senescent cells by senolytics and senomorphics, which could selectively eliminate senescent cells or inhibit their senescence-associated secretory phenotype (SASP) secretion, have been increasingly explored. Importantly, many natural products with promising biological activity extracted from food or medicine–food homology have the above-mentioned effects. Furthermore, the identification of the target cells or target proteins of these natural products is of great significance for the indication of their mechanism of action, and it also lays a scientific foundation for the realization of precision nutrition intervention in the future. This review details how senescent cells affect CVDs, how natural products target senescent cells through nutritional intervention, and research methods for natural products in cardiovascular aging. Full article

The world is characterised by the growing volumes and flow of goods, which, amid benefits to economic development, result in negative externalities affecting the sustainability of cities. Although numerous studies have analysed the locational patterns of logistics facilities in cities, further research is required to examine their real estate patterns and trends. The aim of the paper is, therefore, to analyse the value of land accommodating logistics facilities in the City of Cape Town municipality, South Africa. Given the lack of dedicated geo-spatial data, logistics firms were searched on Google Maps, utilising a combination of aerial photography and street view imagery. Three main attributes of land parcels hosting logistics facilities were thereafter captured from the municipal cadastral information: property extent, street address, and property number. The latter two were used to extract the 2018 and 2022 property market values from the valuation rolls on the municipal website, followed by statistical, spatial, and geographically weighted regression (GWR) analyses. Zones near the central business district and seaport, as well as areas with prime road-based accessibility, had high market values, while those near the railway stations did not stand out. However, GWR yielded weak relationships between market values and the locational variables analysed, arguably showing a disconnect between spatial planning and logistics planning. Towards augmenting sustainable logistics, it is recommended that relevant stakeholders strategically integrate logistics into spatial planning, and particularly revitalise freight rail to attract investment to logistics hubs with direct railway access. Full article

Mycobacterium bovis is the causative pathogen of bovine tuberculosis (bTB), a disease that affects cattle and other mammals, including humans. Currently, there is no efficient vaccine against bTB, underscoring the need for novel immunization strategies. The M72 fusion protein, composed of three polypeptides derived from Mycobacterium tuberculosis and M. bovis, has demonstrated protective efficacy against M. tuberculosis in clinical trials when combined with the AS01E adjuvant. Given the established efficacy of nanocapsule formulations as vaccine delivery systems, this study evaluated a novel immunization strategy combining BCG with either full-length M72 or a truncated M72 fused to a streptococcal albumin-binding domain (ABDsM72). Both antigens were encapsulated in chitosan/alginate nanocapsules and assessed in a murine M. bovis challenge model. Priming with BCG followed by an M72 boost significantly improved splenic protection compared to BCG alone, but it did not enhance pulmonary protection. Notably, boosting with ABDsM72 further increased the proportion of CD4+KLRG1-CXCR3+ T cells in the lungs of M. bovis-challenged mice, a key correlate of protective immunity. These findings demonstrate that chitosan/alginate-encapsulated antigens enhance BCG-induced immunity, supporting their potential as next-generation vaccine candidates for bTB control. Full article

Epigenetic rearrangements can create a favorable environment for the intrinsic plasticity of brain cells, leading to cellular reprogramming into virtually any cell type through the induction of cell-specific transcriptional programs. In this study, we assessed how chromatin remodeling induced by broad-spectrum HDAC inhibitors affects cellular differentiation trajectories in rat primary neuron–glia cultures using a combination of transcriptomics, qPCR, and cytochemistry. We described the epigenetic regulation of transcriptional programs controlled by master transcription factors and neurotrophins in the context of neuronal and glial differentiation and evaluated the expression of representative cell-specific markers. The results obtained suggest that HDAC inhibitors reduce the proliferative potential of cultured cells and induce transcriptomic changes associated with cell differentiation and specialization. Particularly, we revealed a significant upregulation of genes typically expressed in neuromodulatory neurons and the downregulation of genes expressed in glia and inhibitory neurons. Transcriptional changes were accompanied by continuous elevation of histone serotonylation levels in both neurons and glia. Emerging shortly after HDAC inhibition, a complex chromatin remodeling, which includes histone serotonylation, persists over many hours in distinct brain cells. We assume that this sustained epigenetic mechanism likely helps to maintain transcriptional changes associated with cell fate commitment, possibly priming cells for long-term fate conversion. Full article

Obesity and its related comorbidities continue to be a primary public health concern, especially in the United States (US). Such comorbidities include the top two causes of death in the US: cardiovascular disease and cancer. Obesity is also associated with several other chronic conditions that affect millions of adults and children, including diabetes, kidney, and liver disease. Weight loss has long been considered the front-line treatment and prevention strategy for these conditions. Lifestyle approaches, including dietary modification and increasing physical activity, are typically recommended for individuals with obesity, although rates of achieving and maintaining clinically meaningful weight loss remain low. Understanding the root causes of minimal weight loss and weight regain has been a prime focus among many researchers over the past several decades. The present review addresses several advantages of prioritizing exercise as an obesity and chronic disease treatment. We discuss current challenges when exercise is the primary treatment strategy, including physiological parameters that may influence the efficacy of exercise in addition to behavioral and environmental factors that play a role in exercise adherence and adoption. We also explore strategies and principles that, although not commonly utilized in an obesity/chronic disease treatment setting, may be applied and adapted to fit this model. Full article

Background: Lower limb motor output contributes to determining functional performance in many motor tasks. This study investigated the effects of non-invasive spinal cord transcutaneous stimulation (scTS) applied during an exercise-based priming protocol on lower limb muscle force and power generation. Methods: Twelve young, physically active male volunteers (age: 22.7 ± 2.1 years) participated in this randomized crossover, sham-controlled study. The maximal voluntary contraction and low-level torque steadiness of knee extensors, as well as the maximal explosive extension of lower limbs, were assessed before and after the priming protocol with scTS or sham stimulation over a total of four experimental sessions. Further, characteristics of evoked potentials to scTS related to spinal circuitry excitability were assessed in the supine position before and after the scTS priming protocol. The exercise component of the ~25 min priming protocol consisted of low-volume, low- and high-intensity lower limb motor tasks. Results: scTS priming protocol tended to increase or maintain maximum isometric torque during knee extension (4.7%) as well as peak force (0.2%) and rate of force development (6.0%) during explosive lower limb extensions, whereas sham priming protocol tended to decrease them (−4.3%, −3.3%, and −15.1%, respectively). This resulted in significant interactions (p = 0.001 to 0.018) and medium–large differences between scTS and sham protocols. These findings were associated with meaningful trends of some neurophysiological variables. Conversely, priming protocols did not affect low-level torque steadiness. Conclusions: scTS counteracted the unexpected fatigue induced by the exercise-based priming protocol, supporting lower limb performance during maximal efforts. Future studies are warranted to assess the implementation of scTS with optimized exercise-based priming protocols during training and rehabilitation programmes that include high-intensity neuromuscular efforts. Full article