Skin lamellar bodies (LBs) are crucial for forming and renewing the protective skin barrier, which regulates the body’s internal environment and integrity. LB dysfunction is associated with severe disease conditions such as atopic dermatitis, Netherton syndrome and Harlequin ichthyosis, among others. Despite its importance in human physiology, the intracellular origin and biogenesis mechanism of LBs remain largely unknown. LBs are lysosome-related organelles (LRO), a group of cell type-specific organelles having unique structures, cargo content, and function. Classical LROs such as melanosomes, lung lamellar bodies and Weibel-Palade bodies share overlapped molecular machinery/mechanisms and are co-affected in genetic disorders like Hermansky-Pudlak syndrome (HPS) or Chédiak-Higashi syndrome (CHS). In contrast, LBs contain a diverse array of protein and lipid cargo that are notably different from those found in other LROs, and LBs are not reported to be affected in HPS/CHS. LBs form in an advanced differentiation state of keratinocytes while cells are experiencing high ions and low nutrients in their exterior, the plasma membrane (PM) undergoing modifications, and intracellular organelles starting to disappear. This article discusses atypical conditions of LB biogenesis in comparison to classical LROs, which may potentially guide future research on LB biogenesis.
Kazi Mustafizur Rahman, Md Mushfiqur Rahman, Sadia Islam
et al.
The motivation is to develop a device for pacemaker-implanted patients that would automatically alert them in an intense magnetic field. Moreover, the employees working near any strong magnetic environment would benefit by avoiding high exposure. This research delves into a comprehensive process for the implementation and characterization of such a wearable based on the magnetoresistance effect, which is a function of the magnetic field. The program executes on the Arduino IDE platform. Samples are taken for varying magnetic flux density along each axis, for changes in distance of 2.5 mm. The calculations take place accordingly and provide outputs in microtesla units. Subsequently, the device is analyzed by plotting the responses, and it also helps to understand the working procedure. For a certain axis, the magnetic field is generally stronger than others. The goal is to determine the highest absolute value at any instance, including the Earth's geomagnetic field of 22–67 μT. Regulatory standards are followed to divide the magnetic flux density into four states: power saver (below 150 μT), safe (150–500 μT), unsafe (500–750 μT), and danger (over 750 μT). These values consist of ±20 μT error, which is quite insignificant. Depending on the state, the novel device generates different warning signals to mitigate risk from magnetic fields. From the error bar plot, it is realized that the percentage of error decreases while calculating higher magnetic flux. The errors could be reduced remarkably by ensuring better calibration and compensation techniques in the future.
Introduction: Hand hygiene is a cornerstone of infection prevention; however, the water and infrastructure used for handwashing can themselves become sources of microbial contamination. This study assessed the water quality and sanitary conditions of hand hygiene facilities in public and private hospitals in Addis Ababa, Ethiopia. Methods: A laboratory-based cross-sectional study was conducted from May to June 2025 in 10 hospitals. Forty samples were collected, including 20 tap water samples and 20 swab samples from tap handles. A sanitary survey evaluated water supply and hand hygiene stations, with onsite physicochemical measurements, and targeted microbial analyses performed. Data were recorded in an Excel spreadsheet and analyzed using SPSS, employing descriptive statistics and Chi-square tests, with significance defined at P < .05. Results: The sanitary survey showed that 62.5% of hospitals had continuous running water, with 75% of water systems free from leaks. Handwashing stations were accessible in 55% of facilities, primarily hand-operated (67.5%), followed by elbow-operated (25%) and foot-operated (7.5%). Maintenance deficiencies were noted in 37.5% of stations, with soap available at only 55%. Hand drying materials were present in 12.5% of hospitals, and only 45% of facilities reported regular cleaning of handwashing stations. Physicochemical water quality parameters were generally within acceptable limits. Microbiological analysis revealed high contamination: Escherichia coli was detected in 66.7% of all samples, found on 100% of tap handles compared to 31.6% of water samples ( P < .001). Other pathogens included Staphylococcus aureus (55%), Klebsiella (52.5%), Shigella (50%), and Salmonella (50%), all significantly prevalent on swabs than water samples ( P < .001), with no significant difference by hospital ownership. Conclusion: The study found significant microbial contamination in handwashing infrastructure. To reduce risks, facilities should install non-hand-operated stations, enhance routine cleaning and disinfection, and ensure proper maintenance. Regular water quality monitoring and infection control training are essential.
Environmental sciences, Public aspects of medicine
Minjae Kim, Stefano Cazzaniga, Junhwan Jang
et al.
Abstract Background Photosynthetic microalgae are known for their sustainable and eco-friendly potential to convert carbon dioxide into valuable products. Nevertheless, the challenge of self-shading due to high cell density has been identified as a drawback, hampering productivity in sustainable photoautotrophic mass cultivation. To address this issue, mutants with altered pigment composition have been proposed to allow a more efficient light diffusion but further study on the role of the different pigments is still needed to correctly engineer this process. Results We here investigated the Chlamydomonas reinhardtii Δzl mutant with zeaxanthin as the sole xanthophyll. The Δzl mutant displayed altered pigment composition, characterized by lower chlorophyll content, higher chlorophyll a/b ratio, and lower chlorophyll/carotenoid ratio compared to the wild type (Wt). The Δzl mutant also exhibited a significant decrease in the light-harvesting complex II/Photosystem II ratio (LHCII/PSII) and the absence of trimeric LHCIIs. This significantly affects the organization and stability of PSII supercomplexes. Consequently, the estimated functional antenna size of PSII in the Δzl mutant was approximately 60% smaller compared to that of Wt, and reduced PSII activity was evident in this mutant. Notably, the Δzl mutant showed impaired non-photochemical quenching. However, the Δzl mutant compensated by exhibiting enhanced cyclic electron flow compared to Wt, seemingly offsetting the impaired PSII functionality. Consequently, the Δzl mutant achieved significantly higher cell densities than Wt under high-light conditions. Conclusions Our findings highlight significant changes in pigment content and pigment–protein complexes in the Δzl mutant compared to Wt, resulting in an advantage for high-density photoautotrophic cultivation. This advantage is attributed to the decreased chlorophyll content of the Δzl mutant, allowing better light penetration. In addition, the accumulated zeaxanthin in the mutant could serve as an antioxidant, offering protection against reactive oxygen species generated by chlorophylls.
Abstract Immune checkpoint blockers (ICBs) have been applied for cancer therapy and achieved great success in the field of cancer immunotherapy. Nevertheless, the broad application of ICBs is limited by the low response rate. To address this issue, increasing studies have found that the induction of immunogenic cell death (ICD) in tumor cells is becoming an emerging therapeutic strategy in cancer treatment, not only straightly killing tumor cells but also enhancing dying cells immunogenicity and activating antitumor immunity. ICD is a generic term representing different cell death modes containing ferroptosis, pyroptosis, autophagy and apoptosis. Traditional chemotherapeutic agents usually inhibit tumor growth based on the apoptotic ICD, but most tumor cells are resistant to the apoptosis. Thus, the induction of non-apoptotic ICD is considered to be a more efficient approach for cancer therapy. In addition, due to the ineffective localization of ICD inducers, various types of nanomaterials have been being developed to achieve targeted delivery of therapeutic agents and improved immunotherapeutic efficiency. In this review, we briefly outline molecular mechanisms of ferroptosis, pyroptosis and autophagy, as well as their reciprocal interactions with antitumor immunity, and then summarize the current progress of ICD-induced nanoparticles based on different strategies and illustrate their applications in the cancer therapy. Graphical Abstract
Arjet Nievergeld, Judith Fonken, Esther Maas
et al.
Image-based patient-specific rupture risk analysis for abdominal aortic aneurysms (AAAs) has shown considerable promise. However, clinical translation has been hampered by the use of invasive and costly imaging modalities. Despite being a promising alternative, ultrasound (US) makes a full analysis, including intraluminal thrombus (ILT), not trivial. This study explored the feasibility of assessing AAA rupture risk parameters, e.g., peak wall stress (PWS) and peak wall rupture index (PWRI), using US-based models of the AAA wall, finally including ILT. Three-dimensional US data were segmented from a group of AAA patients whose CT data were available within 30 days. The segmented vessel wall and ILT boundaries were converted into a mesh including and excluding ILT to evaluate the effect of adding ILT on the model output. US-based rupture risk parameters (PWS and PWRI) were compared to CT-based results. The US-based PWS and PWRI, including ILT, showed good agreement with CT-based results, and the model excluding ILT showed no significant bias in wall stress or rupture index. When including ILT, a lower US-based wall stress and rupture index of 7.2% and 3.8% were found, respectively. The intraclass correlation coefficient (ICC) of PWS was 0.60. The highest ICC was found for the PWRI (ICC = 0.86), indicating good absolute agreement. This study showed that PWRI can be estimated with US when including the ILT, yielding comparable results to CT, and good absolute agreement. Future work should focus on improving the contrast of ILT in US, since this will be essential to performing large-scale studies in AAA cohorts.
The eggshell (ES) provides protection against pathogenic and physical insults while supplying essential metabolic and nutritional needs for the growing avian embryo. It is constituted mainly of calcium carbonate arranged as calcite crystals. The global chicken egg production in 2018 was over 76.7 million metric tons. In industrialized countries, about 30% of eggs are processed at breaker plants that produce liquid egg products and large quantities of solid ES waste. ES waste is utilized for a variety of low-value applications, or alternatively is disposed in landfill with associated economic and environmental burdens. The number of patents pertaining to ES applications has increased dramatically in recent years; of 673 patents granted in the last century, 536 (80%) were published in the last two decades. This review provides a snapshot of the most recent patents published between 2015 and 2020, with emphasis on different biotechnological applications of ES waste, and summarizes applications for biomedical, chemical, engineering, and environmental technologies. Biomedical technologies include the production of calcium lactate, calcium phosphate, and health-promoting products, while chemical technologies include plant growth promoters, food processing and production, and biodiesel oil catalysis along with active calcium, carbon, soluble proteins, organic calcium, and ultrafine calcium carbonate sources. Engineering technologies address material engineering and nanoparticle production, while environmental technologies pertain to production of biomass, solubilization of sludge as well as production of magnetic ES adsorbents and adsorption of heavy metals, organics, total nitrogen and fluoride, soil pollutants, and radioactive compounds. Although the number of ES-based patents has exponentially increased in the last decade, exploration of innovative top-down approaches and ES development as a physical platform are new endeavors that are expected to further increase the upscaling of ES waste exploitation.
Amycolatopsis is an important source of diverse valuable bioactive natural products. The CRISPR/Cas-mediated gene editing tool has been established in some Amycolatopsis species and has accomplished the deletion of single gene or two genes. The goal of this study was to develop a high-efficient CRISPR/Cas9-mediated genome editing system in vancomycin-producing strain A. keratiniphila HCCB10007 and enhance the production of vancomycin by deleting the large fragments of ECO-0501 BGC. By adopting the promoters of gapdhp and ermE*p which drove the expressions of scocas9 and sgRNA, respectively, the all-in-one editing plasmid by homology-directed repair (HDR) precisely deleted the single gene gtfD and inserted the gene eGFP with the efficiency of 100%. Furthermore, The CRISPR/Cas9-mediated editing system successfully deleted the large fragments of cds13-17 (7.7 kb), cds23 (12.7 kb) and cds22-23 (21.2 kb) in ECO-0501 biosynthetic gene cluster (BGC) with high efficiencies of 81%–97% by selecting the sgRNAs with a suitable PAM sequence. Finally, a larger fragment of cds4-27 (87.5 kb) in ECO-0501 BGC was deleted by a dual-sgRNA strategy. The deletion of the ECO-0501 BGCs revealed a noticeable improvement of vancomycin production, and the mutants, which were deleted the ECO-0501 BGCs of cds13-17, cds22-23 and cds4-27, all achieved a 30%–40% increase in vancomycin yield. Therefore, the successful construction of the CRISPR/Cas9-mediated genome editing system and its application in large fragment deletion in A. keratiniphila HCCB10007 might provide a powerful tool for other Amycolatopsis species.
Abstract Brewers’ spent grain (BSG) is the amplest by-product of the brewing process. The fresh BSG is currently used as low-cost cattle feed due to its microbiological instability and high perishability. While recent research looked at the effects of storage time and temperature on the characteristics of wet brewers grains (WBG) as ruminant feeds. Three storage temperatures (15, 20, and 25 °C) and periods (2, 4 and 6 days) were arranged in a 3 × 3 factorial design. Surface spoilage was not apparent at 15 °C throughout the storage periods. Deterioration was not also observed at 20 °C until the fourth day of storage where slight mold growth was apparent. Extensive mold growth was detected late in the sixth day at 20 °C and continued manifestations up until the last day of storage at 25 °C. Changes in major nutrients, DM losses, and yeast and mold colony count were significantly affected by the interaction of storage temperatures and durations (P < 0.05). Except for samples stored at 15 °C, nutrients contents decreased concomitantly (exceptions are ADF, lignin, and loss in DM) with prolonged storage times (p < 0.05) and increasing temperatures (p < 0.05). Contrast analysis indicated that it would be safe to store under aerobic storage conditions and feed the WBG for dairy cattle.
Stanisław Malicki, Barbara Pucelik, Edyta Żyła
et al.
Immune checkpoint targeting immunotherapy has revolutionized the treatment of certain cancers in the recent years. Determination of the status of immune checkpoint expression in particular cancers may assist decision making. Here, we describe the development of a single-stranded aptamer-based molecular probe specifically recognizing human PD-L1. Target engaging aptamers are selected by iterative enrichment from a random ssDNA pool and the binding is characterized biochemically. Specificity and dose dependence is demonstrated in vitro in the cell culture using human kidney tumor cells (786-0), human melanoma cells (WM115 and WM266.4) and human glioblastoma LN18 cancer cells. The utility of the probe in vivo is demonstrated using two mouse tumor models, where we show that the probe exhibits excellent potential in imaging. We postulate that further development of the probe may allow universal imaging of different types of tumors depending on their PD-L1 status, which may find utility in cancer diagnosis.
Janina Ličytė, Kotryna Kvederavičiūtė, Audronė Rukšėnaitė
et al.
The formation of three oxidative DNA 5-methylcytosine (5mC) modifications (oxi-mCs)—5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC)—by the TET/JBP family of dioxygenases prompted intensive studies of their functional roles in mammalian cells. However, the functional interplay of these less abundant modified nucleotides in other eukaryotic lineages remains poorly understood. We carried out a systematic study of the content and distribution of oxi-mCs in the DNA and RNA of the basidiomycetes Laccaria bicolor and Coprinopsis cinerea, which are established models to study DNA methylation and developmental and symbiotic processes. Quantitative liquid chromatography–tandem mass spectrometry revealed persistent but uneven occurrences of 5hmC, 5fC and 5caC in the DNA and RNA of the two organisms, which could be upregulated by vitamin C. 5caC in RNA (5carC) was predominantly found in non-ribosomal RNA, which potentially includes non-coding, messenger and small RNA species. Genome-wide mapping of 5hmC and 5fC using the single CG analysis techniques hmTOP-seq and foTOP-seq pointed at involvement of oxi-mCs in the regulation of gene expression and silencing of transposable elements. The implicated diverse roles of 5mC and oxi-mCs in the two fungi highlight the epigenetic importance of the latter modifications, which are often neglected in standard whole-genome bisulfite analyses.
Summary: Due to lack of the kernel awareness, some popular deep image reconstruction networks are unstable. To address this problem, here we introduce the bounded relative error norm (BREN) property, which is a special case of the Lipschitz continuity. Then, we perform a convergence study consisting of two parts: (1) a heuristic analysis on the convergence of the analytic compressed iterative deep (ACID) scheme (with the simplification that the CS module achieves a perfect sparsification), and (2) a mathematically denser analysis (with the two approximations: [1] AT is viewed as an inverse A-1 in the perspective of an iterative reconstruction procedure and [2] a pseudo-inverse is used for a total variation operator H). Also, we present adversarial attack algorithms to perturb the selected reconstruction networks respectively and, more importantly, to attack the ACID workflow as a whole. Finally, we show the numerical convergence of the ACID iteration in terms of the Lipschitz constant and the local stability against noise. The bigger picture: For deep tomographic reconstruction to realize its full potential in practice, it is critically important to address the instabilities of deep reconstruction networks, which were identified in a recent PNAS paper. Our analytic compressed iterative deep (ACID) framework has provided an effective solution to address this challenge by synergizing deep learning and compressed sensing through iterative refinement. Here, we provide an initial convergence analysis, describe an algorithm to attack the entire ACID workflow, and establish not only its capability of stabilizing an unstable deep reconstruction network but also its stability against adversarial attacks dedicated to ACID as a whole. Although our theoretical results are under approximations, they shed light on the converging mechanism of ACID, serving as a basis for further investigation.