Metabolic landscape of human alveolar type II epithelial cells undergoing epithelial-mesenchymal transition induced directly by silica exposure.

Epithelial-mesenchymal transition (EMT) plays an irreplaceable role in the development of silicosis. However, molecular mechanisms of EMT induced by silica exposure still remain to be addressed. Herein, metabolic profiles of human alveolar type II epithelial cells (A549 cells) exposed directly to silica were characterized using non-targeted metabolomic approaches. A total of 84 differential metabolites (DMs) were identified in silica-treated A549 cells undergoing EMT, which were mainly enriched in metabolisms of amino acids (e.g., glutamate, alanine, aspartate), purine metabolism, glycolysis, etc. The number of DMs identified in the A549 cells obviously increased with the elevated exposure concentration of silica. Remarkably, glutamine catabolism was significantly promoted in the silica-treated A549 cells, and the levels of related metabolites (e.g., succinate) and enzymes (e.g., α-ketoglutarate (α-KG) dehydrogenase) were substantially up-regulated, with a preference to α-KG pathway. Supplementation of glutamine into the cell culture could substantially enhance the expression levels of both EMT-related markers and Snail (zinc finger transcription factor). Our results suggest that the EMT of human alveolar epithelial cells directly induced by silica can be essential to the development of silicosis.

HLA Awareness in tissue decellularization: A paradigm shift for enhanced biocompatibility, studied on the model of the human fascia lata graft.

Last twenties, tissue engineering has rapidly advanced to address the shortage of organ donors. Decellularization techniques have been developed to mitigate immune rejection and alloresponse in transplantation. However, a clear definition of effective decellularization remains elusive. This study compares various decellularization protocols using the human fascia lata model. Morphological, structural and cytotoxicity/viability analyses indicated that all the five tested protocols were equivalent and met Crapo's criteria for successful decellularization. Interestingly, only the in vivo immunization test on rats revealed differences. Only one protocol exhibited Human Leucocyte Antigen (HLA) content below 1% residual threshold, the only criterion preventing rat immunization with an absence of rat anti-human IgG switch after one month (N=4 donors for each of the 7 groups, added by negative and positive controls, n=28). By respecting a refined set of criteria, i.e. lack of visible nuclear material, <50ng DNA/mg dry weight of extracellular matrix, and <1% residual HLA content, the potential for adverse host reactions can be drastically reduced. In conclusion, this study emphasizes the importance of considering not only nuclear components but also major histocompatibility complex in decellularization protocols and proposes new guidelines to promote safer clinical development and use of bioengineered scaffolds.

Corneal stromal structure replicating humanized hydrogel patch for sutureless repair of deep anterior-corneal defect.

A critical shortage of donor corneas exists worldwide. Hydrogel patches with a biological architecture and functions that simulate those of native corneas have garnered considerable attention. This study introduces a stromal structure replicating corneal patch (SRCP) composed of a decellularized cornea-templated nanotubular skeleton, recombinant human collagen, and methacrylated gelatin, exhibiting a similar ultrastructure and transmittance (above 80 %) to natural cornea. The SRCP is superior to the conventional recombinant human collagen patch in terms of biomechanical properties and resistance to enzymatic degradation. Additionally, SRCP promotes corneal epithelial and stromal cell migration while preventing the trans-differentiation of stromal cells into myofibroblasts. When applied to an ocular surface (37 °C), SRCP releases methacrylated gelatin, which robustly binds SRCP to the corneal stroma after activation by 405 nm light. Compared to gelatin-based photocurable hydrogel, the SRCP better supports the restoration of normal corneal curvature and withstands deformation under an elevated intraocular pressure (100 mmHg). In an in vivo deep anterior-corneal defect model, SRCP facilitated epithelial healing and vision recovery within 2 weeks, maintained graft structural stability, and inhibited stromal scarring at 4 weeks post-operation. The ideal performance of the SRCP makes it a promising humanized corneal equivalent for sutureless clinical applications.

Gradient conducting polymer surfaces with netrin-1-conjugation promote axon guidance and neuron transmission of human iPSC-derived retinal ganglion cells.

Major advances have been made in utilizing human-induced pluripotent stem cells (hiPSCs) for regenerative medicine. Nevertheless, the delivery and integration of hiPSCs into target tissues remain significant challenges, particularly in the context of retinal ganglion cell (RGC) restoration. In this study, we introduce a promising avenue for providing directional guidance to regenerated cells in the retina. First, we developed a technique for construction of gradient interfaces based on functionalized conductive polymers, which could be applied with various functionalized ehthylenedioxythiophene (EDOT) monomers. Using a tree-shaped channel encapsulated with a thin PDMS and a specially designed electrochemical chamber, gradient flow generation could be converted into a functionalized-PEDOT gradient film by cyclic voltammetry. The characteristics of the successfully fabricated gradient flow and surface were analyzed using fluorescent labels, time of flight secondary ion mass spectrometry (TOF-SIMS), and X-ray photoelectron spectroscopy (XPS). Remarkably, hiPSC-RGCs seeded on PEDOT exhibited improvements in neurite outgrowth, axon guidance and neuronal electrophysiology measurements. These results suggest that our novel gradient PEDOT may be used with hiPSC-based technologies as a potential biomedical engineering scaffold for functional restoration of RGCs in retinal degenerative diseases and optic neuropathies.

Strategies for improving expression of recombinant human chorionic gonadotropin in Chinese Hamster Ovary (CHO) cells.

Optimizations of the gene expression cassette combined with the selection of an appropriate signal peptide are important factors that must be considered to enhance heterologous protein expression in Chinese Hamster Ovary (CHO) cells. In this study, we investigated the effectiveness of different signal peptides on the production of recombinant human chorionic gonadotropin (r-hCG) in CHO-K1 cells. Four optimized expression constructs containing four promising signal peptides were stably transfected into CHO-K1 cells. The generated CHO-K1 stable pool was then evaluated for r-hCG protein production. Interestingly, human serum albumin and human interleukin-2 signal peptides exhibited relatively greater extracellular secretion of the r-hCG with an average yield of (16.59 ± 0.02 µg/ml) and (14.80 ± 0.13 µg/ml) respectively compared to the native and murine IgGκ light chain signal peptides. The stably transfected CHO pool was further used as the cell substrate to develop an optimized upstream process followed by a downstream phase of the r-hCG. Finally, the biological activity of the purified r-hCG was assessed using in vitro bioassays. The combined data highlight that the choice of signal peptide can be imperative to ensure an optimal secretion of a recombinant protein in CHO cells. In addition, the stable pool technology was a viable approach for the production of biologically active r-hCG at a research scale with acceptable bioprocess performances and consistent product quality.

Profiles, exposure assessment and expanded screening of PAHs and their derivatives in one petroleum refinery facility of China.

This study investigated environmental distribution and human exposure of polycyclic aromatic hydrocarbons (PAHs) and their derivatives in one Chinese petroleum refinery facility. It was found that, following with high concentrations of 16 EPA PAHs (∑Parent-PAHs) in smelting subarea of studied petroleum refinery facility, total derivatives of PAHs [named as XPAHs, including nitro PAHs (NPAHs), chlorinated PAHs (Cl-PAHs), and brominated PAHs (Br-PAHs)] in gas (mean= 1.57 × 104 ng/m3), total suspended particulate (TSP) (mean= 4.33 × 103 ng/m3) and soil (mean= 4.37 × 103 ng/g) in this subarea had 1.76-6.19 times higher levels than those from other subareas of this facility, surrounding residential areas and reference areas, indicating that petroleum refining processes would lead apparent derivation of PAHs. Especially, compared with those in residential and reference areas, gas samples in the petrochemical areas had higher ∑NPAH/∑PAHs (mean=2.18), but lower ∑Cl-PAH/∑PAHs (mean=1.43 × 10-1) and ∑Br-PAH/∑PAHs ratios (mean=7.49 × 10-2), indicating the richer nitrification of PAHs than chlorination during petrochemical process. The occupational exposure to PAHs and XPAHs in this petroleum refinery facility were 24-343 times higher than non-occupational exposure, and the ILCR (1.04 × 10-4) for petrochemical workers was considered to be potential high risk. Furthermore, one expanded high-resolution screening through GC Orbitrap/MS was performed for soils from petrochemical area, and another 35 PAHs were found, including alkyl-PAHs, phenyl-PAHs and other species, indicating that profiles and risks of PAHs analogs in petrochemical areas deserve further expanded investigation.

Assessment of internal exposure risk from metals pollution of occupational and non-occupational populations around a non-ferrous metal smelting plant.

Non-ferrous metal smelting poses significant risks to public health. Specifically, the copper smelting process releases arsenic, a semi-volatile metalloid, which poses an emerging exposure risk to both workers and nearby residents. To comprehensively understand the internal exposure risks of metal(loid)s from copper smelting, we explored eighteen metal(loid)s and arsenic metabolites in the urine of both occupational and non-occupational populations using inductively coupled plasma mass spectrometry with high-performance liquid chromatography and compared their health risks. Results showed that zinc and copper (485.38 and 14.00 µg/L), and arsenic, lead, cadmium, vanadium, tin and antimony (46.80, 6.82, 2.17, 0.40, 0.44 and 0.23 µg/L, respectively) in workers (n=179) were significantly higher compared to controls (n=168), while Zinc, tin and antimony (412.10, 0.51 and 0.15 µg/L, respectively) of residents were significantly higher than controls. Additionally, workers had a higher monomethyl arsenic percentage (MMA%), showing lower arsenic methylation capacity. Source appointment analysis identified arsenic, lead, cadmium, antimony, tin and thallium as co-exposure metal(loid)s from copper smelting, positively relating to the age of workers. The hazard index (HI) of workers exceeded 1.0, while residents and control were approximately at 1.0. Besides, all three populations had accumulated cancer risks exceeding 1.0 × 10-4, and arsenite (AsIII) was the main contributor to the variation of workers and residents. Furthermore, residents living closer to the smelting plant had higher health risks. This study reveals arsenic exposure metabolites and multiple metals as emerging contaminants for copper smelting exposure populations, providing valuable insights for pollution control in non-ferrous metal smelting.

Generating ESC-Derived RGCs for Cell Replacement Therapy.

In several ocular diseases, degeneration of retinal neurons can lead to permanent blindness. Transplantation of stem cell (SC)-derived RGCs has been proposed as a potential therapy for RGC loss. Although there are reports of successful cases of SC-derived RGC transplantation, achieving long-distance regeneration and functional connectivity remains a challenge. To address these hurdles, retinal organoids are being used to study the regulatory mechanism of stem cell transplantation. Here we present a modified protocol for differentiating human embryonic stem cells (ESCs) into retinal organoids and transplanting organoid-derived RGCs into the murine eyes.

Estudo longitudinal de famílias / Longitudinal study of families / Estudio longitudinal de familias

Introdução: O desenvolvimento da família é influenciado por diversos fatores de sua organização interna e de ordem ambiental, social, cultural, econômica e política. Em contexto de pobreza os riscos são maiores. Fatores de proteção, como boa organização familiar e rede social de apoio podem diminuir as consequências negativas da pobreza. São escassas as pesquisas longitudinais sobre vulnerabilidade e resiliência nas famílias. Objetivo: Este artigo descreve o desenvolvimento de três famílias ao longo de 15 anos, estudadas por meio de entrevistas em casa, parte de uma coorte populacional de um bairro de Porto Alegre (RS). Buscaram-se associações entre a qualidade das relações nessas famílias e sua saúde física e mental, especialmente a do filho, foco da pesquisa. Métodos: Selecionaram-se no arquivo da pesquisa as três primeiras famílias (do total de 148) das quais se tinham os resultados completos das cinco visitas realizadas aos quatro meses e aos dois, quatro, nove e 15 anos de um filho. Realizou-se análise qualitativa dos registros em busca de categorias para compreender a vida e as relações interpessoais nas famílias. O estudo foi realizado em conjunto por duas pesquisadoras, médicas especialistas em desenvolvimento humano. As categorias identificadas na análise e estudadas nas cinco etapas foram: configuração familiar, situação socioeconômica, situações traumáticas, saúde física, saúde relacional e mental, evolução cognitiva e escolar do filho. Resultados: As três famílias, todas de classe C, com filhos sem problemas de saúde física, tiveram evolução suficientemente boa, apesar de todas enfrentarem múltiplos problemas, inclusive separações e mortes precoces. A relação com o sistema de saúde e escola era boa e similar para as três. A jovem com menos problemas de saúde mental foi aquela que sofreu perdas mais importantes: morte dos pais. Tinha uma estrutura familiar multigeracional sólida desde a primeira infância, com relações interpessoais predominantemente colaborativas e amorosas. Conclusões: O artigo busca avançar na compreensão da resiliência nas famílias em situações de vulnerabilidade. Concluímos que essas três famílias, uma delas mais que as outras, foram suficientemente saudáveis na tarefa de educar seus filhos sem desenvolverem problemas mentais graves. Propomos que o bom desenvolvimento se associa com a adequação e amorosidade dos cuidados com a etapa do ciclo vital, mesmo enfrentando situações problemáticas. Essas qualidades precisam estar associadas à estabilidade socioeconômica básica e a bons serviços de saúde e escola.

Introduction: Family development is influenced by it's internal organization and environmental factors, socioeconomic, cultural and political. In poor contexts there are more risks to development. Protection factors like good family organization and social network may decrease the risks. Longitudinal research about vulnerability and resilience in families is scarse. Objective: This article describes the development of three families over 15 years through interviews at home. The families were part of a populational cohort of a neighborhood in Porto Alegre (RS). We looked for links between the quality of relationships and the physical and mental health of these families, especially of the child focus of the research. Methods: We selected in the research archives the first three families (of a total of 148) for which we had full results of the five interviews at four months and two, four, nine and fifteen years of a child. We did a qualitative analysis of the records looking for parameters to understand the life and interpersonal relationships of these families. This study was done by two researchers, both experts in Human Development. The categories identified in the analysis of the five phases were: family structure, socioeconomic situation, traumatic experiences, physical, mental and relational health and cognitive evolution of the child. Results: All three families belonged to economical class C. The children were in good physical health and had sufficiently good general development, having faced multiple problems, including parental separation and early parental death. The relationship with the health and school systems was good in all of them. The youth with less mental health problems was the one who suffered the heaviest loss: early death of both parents. Her family had strong multigenerational ties since her early days, with predominant collaborative and loving relationships. Conclusions: This article aims to contribute to the comprehension of resilience in families in the context of vulnerability. We can say that these three families were healthy enough in the task of bringing up children without any serious mental health problem. We suggest that healthy development is associated with loving interfamily relationships adequate to each phase of development, notwithstanding dramatic events. This needs to be supported by basic economic stability and adequate school and health systems.

Introducción: El desarrollo de la familia es influenciado por su organización interna y factores ambientales, sociales, culturales, económicos y políticos. En contextos pobres los riesgos son mayores. Factores de protección como buena organización familiar y red social de apoyo pueden disminuir las consecuencias negativas de la pobreza. Son pocas las investigaciones longitudinales de vulnerabilidad y resiliencia de las familias. Objetivo: Este artículo describe el estudio del desarrollo de tres familias a lo largo de 15 años, a través de entrevistas en domicilio, parte de una cohorte poblacional de un barrio de Porto Alegre (RS). Se buscaron correlaciones entre la calidad de las relaciones de esas familias y su salud física y mental, especialmente la del hijo foco de la investigación. Métodos: Fueron seleccionadas en el archivo de la investigación las tres primeras familias (de un total de 148) de las cuales se tenían los resultados completos de las cinco visitas realizadas, a los 4 meses, y a los 2, 4, 9, y 15 años de un hijo. Fue realizado un análisis cualitativo de los registros en busca de categorías para comprender la vida y las relaciones interpersonales en las familias. El estudio fue hecho en conjunto por dos investigadoras, médicas especialistas en desarrollo humano. Las categorías identificadas en el análisis y estudiadas en las cinco etapas fueron: configuración familiar, situación socioeconómica, situaciones traumáticas, salud física, salud relacional y mental, evolución cognitiva y escolar del hijo. Resultados: Las tres familias, todas de clase C, con hijos sin problemas de salud física, tuvieron evolución suficientemente buena, a pesar de que todas enfrentaron múltiples problemas, incluso separaciones y muertes precoces. La relación con el sistema de salud y escuela era buena y similar para las tres. La joven con menos problemas de salud mental fue aquella que sufrió las mayores pérdidas: muerte de los padres. Tenía una estructura familiar multigeneracional sólida desde la primera infancia, con relaciones interpersonales predominantemente colaborativas y amorosas. Conclusiones: El artículo pretende avanzar en la comprensión de la resiliencia en las familias en situaciones de vulnerabilidad. Concluimos que esas tres familias, una de ellas más que las otras, fueron suficientemente saludables en la tarea de educar a sus hijos sin que desarrollaran problemas mentales graves. Proponemos que el buen desarrollo se asocia con el amor y adecuación de los cuidados a la etapa del ciclo vital, aun enfrentando situaciones problemáticas. Esas calidades necesitan estar asociadas a la estabilidad socioeconómica básica y buenos servicios de salud y escuela.

Habitat suitability and protected area coverage for an expanding cougar Puma concolor population in Canada.

Successful conservation of expanding large carnivore populations and management of human-wildlife conflict to promote coexistence requires sufficient spatiotemporal knowledge to inform appropriate action. In Canada, cougars (Puma concolor) are expanding their range eastwards and little research is available for use in decision making by land managers and conservation planners. To inform proactive management regarding expanding populations of cougars in Canada, we utilized open-source cougar presence and land-cover data in a maximum entropy habitat suitability model to determine potentially suitable habitat for cougars across the country. We then used a gap analysis to determine the effectiveness of existing formal protected areas to protect potential cougar habitat. Suitable habitat exists for range-expanding cougars dispersing eastwards through the central and eastern provinces to the Atlantic coast. While the habitat is highly fragmented, the highest suitability occurs in areas of medium road density, indicating that the potential for new human-cougar conflict will likely involve residents of exurban and rural areas. Protected areas offered 16% coverage of suitable habitat, although most protected areas that overlap predicted cougar habitat are not large enough to effectively conserve the large home range requirements of cougars. Synthesis and Applications: High fragmentation of suitable habitat and the potential for human-wildlife conflict requires proactive management to ensure appropriately sized and connected areas are maintained for the establishment of expanding cougar populations. Many of the management actions intended to aid in the conservation of cougars and their habitat can also serve to mitigate potential human-cougar conflict arising as a consequence of an expanding population, such as highway wildlife crossing structures and formal habitat protection.

Knowledge, Attitude, and Perception Regarding the Human Papillomavirus (HPV) Vaccine Among Parents at Al-Madinah Al-Munawwar: A Cross-Sectional Study.

BACKGROUND:  Human papillomavirus (HPV) is the leading cause of cervical cancer in reproductive-age Saudi women. Parents' understanding and attitude regarding HPV vaccination in young girls are vital to preventing cervical cancer. OBJECTIVE: This study aims to assess the knowledge, attitudes, and perceptions of parents in Al-Madinah Al-Munawwara towards the HPV vaccine and identify factors influencing their decision to vaccinate their children. METHODS: A cross-sectional survey was conducted among 500 parents in Al-Madinah Al-Munawwara. A structured questionnaire was used to collect data on demographics, knowledge about HPV and the HPV vaccine, attitudes towards vaccination, and perceptions of vaccine safety and efficacy. Data were analyzed using Statistical Product and Service Solutions (SPSS, version 21; IBM SPSS Statistics for Windows, Armonk, NY). RESULTS: Parents have 57.6% knowledge about HPV, 69.2% perceive it as dangerous, and 29.8% know its link to cervical cancer. Physicians are the primary source, and 81.2% believe the vaccine protects HPV. Key predictors of vaccine acceptance included higher educational levels, awareness of HPV-related health risks, and recommendations from healthcare professionals. CONCLUSION: The study reveals a lack of knowledge about HPV infection and vaccines among Saudi Arabian parents, with only 7.2% having vaccinated their children, emphasizing the need for education and screening programs.

Assessment of Hip and Lumbar Spine Range of Motion After Total Hip Arthroplasty Using a Single Camera Markerless System.

BACKGROUND: Total hip arthroplasty (THA) is one of the most cost-effective and successful procedures in orthopedics. However, assessing the post-operative range of motion (ROM) remains a challenge due to the limitations of traditional measurement methods. This study aimed to evaluate hip and spine ROM post-operatively and single-leg balance, using a single-camera markerless motion capture system, and compare outcomes with pre-operative ROM and with an age-matched healthy control group. METHODS: An interventional study was conducted from January 2018 to December 2021. Twenty patients with hip osteoarthritis underwent THA and were assessed using a single-camera markerless system (Kinetisense software). Measurements were taken one month pre-operatively and one year post-operatively. RESULTS: Significant improvements were observed in hip and lumbar spine ROM variables after THA. The most notable enhancements were in hip and spinal flexion. Compared to the control group, the THA group showed minor deficits in hip ROM, particularly in external rotation. Single-leg balance demonstrated improved stability post-operatively. CONCLUSIONS: The single-camera markerless motion capture system offers a promising alternative for assessing hip and lumbar spine ROM, presenting potential advantages over manual goniometry and traditional 3D motion capture systems. Using this system for the evaluation of patients after THA, it seems that THA significantly enhances hip and lumbar spine ROM. Future research should focus on validating the accuracy of markerless systems.

Bridging agro-science and human nutrition: zinc nanoparticles and biochar as catalysts for enhanced crop productivity and biofortification.

The integration of zinc nanoparticles (Zn NPs) with biochar offers a transformative approach to sustainable agriculture by enhancing plant productivity and human nutrition. This combination improves soil health, optimizes nutrient uptake, and increases resilience to environmental stressors, leading to superior crop performance. Our literature review shows that combining Zn NPs with biochar significantly boosts the crop nutrient composition, including proteins, vitamins, sugars, and secondary metabolites. This enhancement improves the plant tolerance to environmental challenges, crop quality, and shelf life. This technique addresses the global issue of Zn deficiency by biofortifying food crops with increased Zn levels, such as mung beans, lettuce, tomatoes, wheat, maize, rice, citrus, apples, and microgreens. Additionally, Zn NPs and biochar improve soil properties by enhancing water retention, cation exchange capacity (CEC), and microbial activity, making soils more fertile and productive. The porous structure of biochar facilitates the slow and sustained release of Zn, ensuring its bioavailability over extended periods and reducing the need for frequent fertilizer applications. This synergy promotes sustainable agricultural practices and reduces the environmental footprint of the traditional farming methods. However, potential ecological risks such as biomagnification, nanoparticle accumulation, and toxicity require careful consideration. Comprehensive risk assessments and management strategies are essential to ensure that agricultural benefits do not compromise the environmental or human health. Future research should focus on sustainable practices for deploying Zn NPs in agriculture, balancing food security and ecological integrity and positioning this approach as a viable solution for nutrient-efficient and sustainable agriculture.

A human embryonic stem cell-based model reveals the cell of origin of FOXR2-activated CNS neuroblastoma.

Background: FOXR2-activated central nervous system (CNS) neuroblastoma (CNS NB-FOXR2) is a recently identified subtype of brain tumor characterized by the elevated expression of the transcription factor FOXR2 mainly due to genomic rearrangements. However, the precise pathogenic mechanisms, including the cell type of origin, remain elusive. Methods: A gene expression analysis of patient tumors was performed to identify putative cell types of origin. Based on this prediction, a new human embryonic stem cell-based model was developed to validate the origin and to examine the molecular and cellular mechanisms underlying the formation of CNS NB-FOXR2. Results: Our data showed that CNS NB-FOXR2 tumors express a high level of lineage marker genes associated with the medial ganglionic eminence (MGE), a transient structure located in the developing ventral forebrain. Our model confirmed the cell-type-specific effect of FOXR2 on the proliferation and in vivo tumorigenicity. Additionally, we found that FOXR2 overexpression activated the MEK/ERK signaling pathway through a suppression of the endogenous RAS inhibitor DIRAS3. The MEK inhibitor trametinib suppressed the proliferation of FOXR2-expressing MGE progenitors more than nonexpressing cells. Conclusions: Our study collectively demonstrates that MGE progenitors are the cell of origin of CNS NB-FOXR2 and that FOXR2 activates the MEK/ERK signaling pathway, providing a potential therapeutic target.

Distribution characteristics of human herpes viruses in the lower respiratory tract and their impact on 30-day mortality in community-acquired pneumonia patients.

Human herpes viruses (HHVs) are commonly detected in community-acquired pneumonia (CAP) patients, particularly those with complex complications, attracting increased attention from clinical practitioners. However, the significance of detecting HHVs in bronchoalveolar lavage fluid (BALF) with CAP patients is still unclear. This study retrospectively analyzed BALF samples from 64 CAP patients at the Kunming Third People's Hospital between August 2021 and December 2023. Metagenomic next generation sequencing (mNGS) was conducted on BALF samples during CAP onset. Multivariate Cox regression models were used to identify independent risk factors for 30-day all-cause mortality in CAP. HHVs were found in 84.4% of CAP patients, which were the most common pathogens (45.1%), followed by bacteria (30.2%) and fungi (11.5%). Bacterial-viral co-infections were most common, occurring in 39 patients. Notably, there was no significant difference in HHV presence between severe and non-severe CAP patients (EBV: P = 0.431, CMV: P = 0.825), except for HHV-7 (P = 0.025). In addition, there was no significant difference in the 30-day mortality between HHV positive and HHV negative groups (P = 0.470), as well as between the HHV-7 positive and HHV-7 negative groups (P = 0.910). However, neither HHVs nor HHV-7 was independent risk factors for 30-day mortality in CAP patients (HHVs: HR 1.171, P = 0.888; HHV-7: HR 1.947, P = 0.382). In summary, among the prevalent presence of multiple HHVs, EBV and CMV were the most prevalent in CAP patients. Patients with sCAP were more susceptible to HHV-7 than those with non-sCAP. These results provide valuable insights for clinicians in guiding appropriate interventions for CAP treatment.

Basic human values and the adoption of cryptocurrency.

Cryptocurrency is an attempt to create an alternative to centralized financial systems using blockchain technology. However, our understanding of the psychological mechanisms that drive cryptocurrency adoption is limited. This study examines the role of basic human values in three stages of cryptocurrency adoption-awareness, intention to buy, and ownership-using the Theory of Planned Behavior (TPB). Logistic regression analysis was conducted on a quota sample of 714 German adults, and the results showed that openness-to-change values increased the likelihood of cryptocurrency awareness, while self-enhancement values increased the likelihood of intention to buy and ownership. These findings were consistent even after controlling for demographic characteristics, attitudinal beliefs, and perceived behavioral control, which are important factors in the TPB. The results suggest that basic human values may influence an individual's decision to adopt cryptocurrency, but the transition from awareness to ownership may be influenced by socio-economic opportunities available to interested individuals.

Relevant factors affecting nurse staffing: a qualitative study from the perspective of nursing managers.

Objective: To understand the current situation of nursing manpower allocation, explore the factors affecting nurse staffing, improve nurse staffing level, and provide reference for better formulation of nursing human resources staffing standards. Methods: A descriptive research method was used to conduct semi-structured interviews with 14 nursing managers. The data were analyzed and refined by content analysis. The sample size was subject to content saturation. Results: Nine themes and twenty sub-themes of influencing factors for nursing staffing were identified across four levels: hospital level, department level, patient level, and nurse level. Conclusion: Hospital and department managers need to comprehensively consider the factors of affecting nurse staffing. Adopting multidimensional optimization measures, improving relevant systems, optimizing nurse structure, and establishing flexible and mobile nurse database to cope with public emergencies, so as to effectively improve nurse staffing and nursing service quality.

An organotypic human melanoma-in-skin model as an in vitro tool for testing Vγ9Vδ2-T cell-based immunotherapy.

Background: Despite considerable advancements in cancer immunotherapy, advanced melanoma still presents a substantial clinical challenge. In an effort to explore treatment options, we examined the immunotherapeutic potential of effector Vγ9Vδ2-T cells in vitro in a three-dimensional (3D) human organotypic melanoma-in-skin (Mel-RhS) model. Materials and methods: Vγ9Vδ2-T cells were introduced into Mel-RhS via intradermal injection and cultured within the tissue microenvironment for up to 3 days. Results: Vγ9Vδ2-T cells remained viable for up to 3 days and were in close proximity to or within tumor nests. Upon Mel-RhS dissociation, a fraction was shown to be decorated by melanoma-associated chondroitin sulfate proteoglycan (MCSP), demonstrating their ability to actively navigate the tumor microenvironment and trogocytose cancer cells. Investigation into the apparent trogocytosis revealed an enhanced activated state of MCSP-decorated Vγ9Vδ2-T cells, evidenced by increased expression levels of 4-1BB, NKp44, programmed cell death protein-1 (PD-1), and programmed death-ligand 1 (PD-L1), compared with their MCSP- counterpart. These findings suggest that Vγ9Vδ2-T cells, upon successfully contacting melanoma cells, actively recognize and acquire MCSP from these malignant cells. Evidence of actual tumor cell elimination, although not significant, was only obtained after preincubation of Mel-RhS with pamidronate, a phosphoantigen-inducing agent, indicating the need for additional T cell receptor-mediated signaling for Vγ9Vδ2-T cells to reach their full oncolytic potential. Conclusions: This study highlights the viability and persistence of Vγ9Vδ2-T cells within the 3D microenvironment, their migratory and antitumor functionality, and the suitability of the model for testing T cell-based therapies, contributing both to the understanding of Vγ9Vδ2-T cell biology and their application in cancer immunotherapy.

Fabrication, sustainability, and key performance indicators of bioelectronics via fiber building blocks.

Bioelectronics provide efficient information exchange between living systems and man-made devices, acting as a vital bridge in merging the domains of biology and technology. Using functional fibers as building blocks, bioelectronics could be hierarchically assembled with vast design possibilities across different scales, enhancing their application-specific biointegration, ergonomics, and sustainability. In this work, the authors review recent developments in bioelectronic fiber elements by reflecting on their fabrication approaches and key performance indicators, including the life cycle sustainability, environmental electromechanical performance, and functional adaptabilities. By delving into the challenges associated with physical deployment and exploring innovative design strategies for adaptability, we propose avenues for future development of bioelectronics via fiber building blocks, boosting the potential of "Fiber of Things" for market-ready bioelectronic products with minimized environmental impact.

A multidisciplinary analysis of over 53,000 fascioliasis patients along the 1995-2019 countrywide spread in Vietnam defines a new epidemiological baseline for One Health approaches.

Fascioliasis, only foodborne trematodiasis of worldwide distribution, is caused by Fasciola hepatica and F. gigantica, liver flukes transmitted by freshwater snails. Southern and southeastern Asia is an emerging hot spot of F. gigantica, despite its hitherto less involvement in human infection. In Vietnam, increasing cases have been reported since 1995, whereas only sixteen throughout 1800-1994. A database was created to include epidemiological data of fascioliasis patients from the 63 Vietnam provinces throughout 1995-2019. Case profiles were based on serology, symptoms, eosinophilia, imaging techniques, stool egg finding, and post-specific-treatment recovery. Radio broadcasting about symptoms and costless diagnosis/treatment led patients to hospitals after symptom onset. Yearly case numbers were modelled and spatio-temporally analyzed. Missing data and confounders were assessed. The countrywide spread has no precedent. It started in the central coast, including 53,109 patients, mostly adults and females. Seasonality, linked to vegetable consumption, peaks in June, although the intensity of this peak differs according to relief/climatic zones. Incidence data and logistic regression curves are obtained for the first time in human fascioliasis. Fasciolid hybrids accompanying the spreading F. gigantica flukes, and climate change assessed by risk index correlations, are both ruled out as outbreak causes. Human-guided movements of livestock from an original area prove to be the way used by fasciolids and lymnaeid vectors to expand geographically. Radix viridis, a highly efficient transmitting and colonizing vector, played a decisive role in the spread. The use of irrigated crop fields, widely inhabited by R. viridis, for livestock grazing facilitated the transmission and spread of the disease. General physician awareness and diagnostic capacity improvement proved the successful impact of such knowledge transfer in facilitating and increasing patient infection detection. Information, education and communication to the public by radio broadcasting demonstrated to be very helpful. Fasciola gigantica is able to cause epidemic and endemic situations similar to F. hepatica. The magnitude of the human outbreak in Vietnam is a health wake-up call for southern and southeastern countries of Asia which present the highest human population densities with increasing food demands, uncontrolled livestock inter-country exchange, foreign import practices, and monsoon's increasing climate change impact.