Extracellular vesicle (EV) research has revealed EV involvement in a variety of biological processes, with potential applications in both fundamental research and therapeutic development. EVs of bacterial origin have been implicated in host-immune interactions in the development of a variety of diseases. Despite differences in the membranes of bacterial and mammalian cells, past studies on EV storage conditions have focused on mammalian EVs. In this work, we evaluated the effects of storage temperature on the properties of EVs derived from gram-positive (Bifidobacterium longum) and gram-negative (Escherichia coli) bacteria and stored for a period of 8 weeks. It was hypothesized that storage over time would impact the integrity of the EV samples, particularly at higher temperatures. B. longum EV identity was confirmed by western blotting for lipoteichoic acid, GroEL, and RecA, while E. coli EV identity was confirmed by western blotting for lipopolysaccharide, GroEL, and Flagellin. Using nanoparticle tracking analysis (NTA), we observed no effect of storage on E. coli EV size or concentration but found that storage at 4°C for 4-8 weeks led to increases in B. longum EV size. No significant changes in particle size or concentration after storage were observed with microfluidic resistive pulse sensing (MRPS). An apparent increase in macrophage activation by the EVs was observed after 4 weeks of storage, followed by an apparent decrease in macrophage activation after 8 weeks of storage. Although EV protein concentration was stable with storage, the intensity and definition of some protein bands in gel electrophoresis appeared to decrease over the storage period. Overall, even short-term storage of bacterial EVs led to changes in EV functionality, and size measurements alone were not necessarily indicative of EV stability.
Canada legalized non-medical cannabis in 2018, with marketing and promotion regulated under the Cannabis Act. However, little is known about the promotional practices of licensed cannabis retailers. This study analyzed the online content of Canadian cannabis retailer websites and assessed apparent violations of federal marketing regulations. A cross-sectional content analysis of cannabis retailer websites across all 13 Canadian provinces and territories. Of the 3599 operational licensed cannabis-retail retailers (3368 private and 231 government operated) in Canada in April 2025, we included each of the government-operated cannabis retailer websites (n = 8) and a random sub-sample of private retailer websites (n = 145). Retailer website content was extracted using a standardized codebook comprising 13 promotion-related categories derived from the Cannabis Act to identify apparent violations. One or more apparent marketing violations were identified on 97% of cannabis retailer websites. Apparent violations were somewhat less common among government-operated retailers (75%) than private retailers (97%). Age verification was absent on 8.5% of websites, all of which were privately operated. Inducement-related content was most common apparent violation (86%), followed by endorsements or testimonials (46%), lifestyle promotion (23%), youth-appealing content (23%), and health or cosmetic benefit claims (22%). Promotional content that may contravene the Cannabis Act was commonly observed on Canadian cannabis retailer websites. These findings suggest that gaps exist between regulatory standards and online retail practices within Canada's legal cannabis market. As more jurisdictions consider cannabis legalization, this evidence can help inform the development and enforcement of cannabis promotion-related regulations.
The reciprocal evolutionary processes among phytophagous insects and host plants involve host shift in the herbivorous insects in response to defense chemicals, such as plant-derived terpenoid compounds that comprise a key element for adaptive radiation, leading to chemosensory diversification. To reveal the multimodal chemosensory targets mediating avoidance behavior of insects in response to irritant stimuli, in this study, we explored multimodal target molecules toward (-)-α-thujone, a bicyclic monoterpenoid compound, focusing on the red flour beetle, Tribolium castaneum. The area-preference test revealed significant avoidance behavior in adult T. castaneum toward (-)-α-thujone. We applied systemic RNAi methodology to knock down hypothesized targets; knocking down the resistance to a dieldrin (Rdl) subunit comprising a γ-aminobutyric acid (GABA)-activated receptor significantly suppressed the avoidance behavior toward (-)-α-thujone, rather than l-menthol. Avoidance behaviors were significantly suppressed after knocking down thermo (TcTRPM) and non-thermo (TcTRPL) TRP channels. Subsequently, quantitative reverse transcription (qRT)-PCR-based spatial expression analysis of TcRdl and TcTRPL revealed high TcRdl transcript expression in the head, followed by the antenna, and prominent TcTRPL transcript expression in the head. Furthermore, the reduced avoidance behavior in antenna-dissected and knockdown of the olfactory receptor coreceptor (TcOrco) lines confirmed the involvement of antenna in the underlying mechanism. The results reflected potential molecular targets including non-thermo TRP channel involved in (-)-α-thujone-mediated avoidance behavior in T. castaneum and indicated multimodality, as exhibited by N,N-diethyl-3-methylbenzamide (DEET), the gold standard of repellent, providing useful insight for further research on the development of new repellents and excito-repellents. © 2026 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
CK18-M30 is an emerging biomarker to be used in patients who have liver damage from drugs or other causes and is now commonly used as a marker of liver apoptosis in patients with drug-induced liver damage. To investigate the effects of different storage conditions on the stability of human cytokeratin 18-M30 (CK18-M30) in serum, this study aims to provide data-driven evidence on sample stability for deferred laboratory testing of clinical specimens that cannot be analysed immediately. A total of 22 serum samples from individuals undergoing routine physical examination were collected and had different concentration levels of CK18-M30 in the Fourth Affiliated Hospital, Zhejiang University School. Baseline value from the immediate test. The remaining samples were distributed into five groups. Aliquots stored at -20°C in cryotubes for 3 days and 2-8°C separation gel tube samples for 3 days had >80% concordance with the baseline and were not different (P > 0.05). Conversely, 2-8°C cryotube aliquots stored for 3 or 7 days, as well as 2-8°C separation gel tubes stored for 7 days, had concordance rates below 80%, significantly discrepant from the baseline (P < 0.01). CK18-M30 is relatively stable at -20°C. Between 2 and 8°C, the separation gel tubes were more stable than the aliquot tubes for up to three days. Aliquot tubes stored at 2-8oC were suboptimal, as the CK18-M30 became unstable after 3 days. The demonstrated stability characteristics of serum CK18-M30 are crucial for ensuring trustworthy biomarker-based safety evaluation when immediate analysis is not possible, given its expanding use as a safety and pharmacodynamic biomarker in pharmaceutical research, especially for tracking drug-induced liver injury in clinical trials and pharmacovigilance programs.
Alongshan virus, a segmented RNA virus in the Jingmenvirus group of flaviviruses, was first identified in 2017 in China in patients with tick-borne encephalitis-like illness. Alongshan virus has since been detected in ticks and mammals in several European countries. In this study, we aimed to characterise the temporal and geographical distribution of Alongshan virus in Austria through nationwide tick surveillance combined with serological and molecular screening in individuals with suspected tick-borne encephalitis or tick exposure. In this nationwide molecular and serological observational study, we conducted a PCR-based screening of ticks collected across Austria in 2024, using flagging, animal hosts, and citizen submissions. We also collated genomic data from stored nucleic acid extracts from ticks collected in Austria in 2005 and 2013 in previous surveillance studies and stored extracts of paired tick-human samples collected between 2015 and 2018. Alongshan virus-positive tick samples were subjected to whole-genome sequencing and phylogenetic analysis. In addition to tick samples, blood samples from Austrian patients with reported tick bite or suspected tick-borne encephalitis, submitted to the National Reference Center for Human Arbovirus Infections, Austria, were screened for Alongshan virus infection and subjected to serological and molecular testing. 2952 ticks were collected between Feb 1, 2024, and Dec 6, 2024, from 29 (83%) of 35 NUTS-3 regions in Austria; the median detection rate for Alongshan virus was 1·2% (IQR 0·4-3·5). In addition, 1816 archived tick samples were analysed, with three testing positive for Alongshan virus. For the virus-positive samples, phylogenetic analysis showed that sequences from Austria grouped within the European clade, with Austrian sequences from the same region showing high sequence similarity. 1361 human serum samples collected between March 1, 2023, and May 16, 2025, were assessed for anti-Alongshan virus IgG antibodies. Two individuals had high antibody titres against Alongshan virus proteins VP1a and VP2. Our study shows detection of Alongshan virus in archived tick samples dating back to 2005, representing the earliest documented occurrence of the virus to date and suggesting that Alongshan virus has been circulating in Austria for at least two decades. The detection of Alongshan virus-specific antibody titres in two individuals suggests past infection and previously unrecognised exposure. These results highlight the need for continued molecular surveillance of tick populations and serological monitoring in humans to define the epidemiology and public health relevance of Alongshan virus in Europe. One Health surveillance and Vector monitoring for cross-border pathogens (OH SURVector) and UNITED4Surveillance.
To prolong the storage period of platelets, dimethyl sulfoxide (DMSO) has been used for platelet cryopreservation at -80 °C to prevent cold storage lesions. Nevertheless, it is important to note that DMSO is a toxic chemical agent that may cause adverse effects and potential safety concerns for clinical applications. Therefore, many studies have attempted to reduce the DMSO concentration used for platelet cryopreservation. Based on our previous findings regarding the stability of platelets in platelet-rich plasma stored at -80 °C for 1 month, it is imperative to explore the cryopreservation of platelets in plasma. This study aimed to evaluate the feasibility of storing apheresis platelets in plasma at -80 °C as a supplemental solution in the absence of cryoprotectants, such as DMSO. We used a comprehensive approach, analyzing platelet count, morphology, mitochondrial structure, and metabolomic and proteomic profiles to assess storage lesions. Our findings revealed that platelets stored at -80 °C in plasma maintained a stable cell count and procoagulant function, comparable with those stored with DMSO. Proteomic analysis showed that the fundamental protein composition essential for platelet clotting function was largely preserved, while metabolomic analysis suggested that metabolism had a minimal impact on platelet homeostasis. In vitro assessments showed no significant difference in platelet activation, and in vivo studies confirmed comparable bleeding times and platelet counts posttransfusion. These results demonstrate that storage in plasma at -80 °C effectively preserves platelet viability and functionality over a short period. This study highlights the potential for developing supplementary storage strategies as alternatives to conventional preservation methods, which could improve platelet availability in transfusion medicine.
Seasonal variability in water supply in tropical humid environments makes household water storage essential for reliable domestic access. This study examined water storage practices and determinants of storage behaviour in Iwo Township, Osun State, Nigeria. Using stratified random sampling, 756 households across 4 sections-Gidigbo, Molete, Oke-Oba I, and Oke-Oba II-were surveyed between February and November 2023, prioritising female household heads due to their central role in water management. Household sizes ranged from fewer than 5 members (32.3%) to more than 15 (12.3%), with most comprising 6 to 10 persons (34.0%). Educational levels were predominantly post-primary (57.7%) and tertiary (25.0%), while religious affiliation was split between Islam (51.9%) and Christianity (45.4%). Storage relied mainly on steel and plastic drums (44.2%), followed by buckets (29.5%) and overhead tanks (20.4%), with deep wells and boreholes serving 89.3% of households. Factor analysis identified 8 determinants of storage preferences, explaining 82.7% of the variance: age composition (17.8%), number of toilets (12.2%), water supply reliability (11.6%), religious activities (10.9%), beliefs about storage (9.0%), household assets (8.9%), storage method (6.8%), and alternative sources (5.7%). The Kaiser-Meyer-Olkin measure (0.827) and Bartlett's test (P < .005) confirmed data suitability. Findings indicate that socio-demographic characteristics and household assets influence storage behaviour more than water availability alone. To enhance water security and support SDG 6, interventions should provide affordable household storage, promote safe storage practices through community awareness, incentivise improved behaviours, and integrate storage considerations into urban planning. Effective implementation requires collaboration between local governments, water agencies, and communities to ensure context-sensitive, equitable, and sustainable water management. Understanding How Households Store Water for a Reliable Supply in Tropical Regions In many tropical regions, water supply is not always reliable, so people need to store water for daily use. This study looked at how households in Iwo, Osun State, Nigeria, manage water storage. Researchers surveyed 756 people from four areas between February and November 2023, focusing on women who handle household water. The study found that household factors, like income and family size, had a bigger impact on water storage than the actual availability of water. These factors accounted for 79.18% of the differences in how people stored water. The results show that policies should focus on helping households by providing affordable storage options, training, and awareness programmes. These efforts will improve access to safe water and support Sustainable Development Goal 6 (SDG 6), which aims for clean water and sanitation for all. Future research should explore how household characteristics influence storage choices and address gaps in gender and location representation.
To compare the effect of storage at 2-8°C and -40°C on temperature-sensitive serum complement protein levels, and to determine the optimal storage temperature that preserves sample integrity during transportation and storage. The comparative, laboratory-based, experimental study was conducted at the Immunology Laboratory, Indus Hospital and Health Network, Karachi, from August to November 2022. At the collection point, after centrifugation, a portion of each serum sample was transferred to a separate aliquot and frozen at -40°C, while the remaining serum was retained in the original tube at 2-8°C. Samples were transported to and stored in the laboratory at the same temperatures. They were assayed for temperature-sensitive serum complement proteins 3 and 4 by turbidimetry. Data was analysed using SPSS 21. There were 50 samples that were analysed. Coefficient of variation at the two temperatures was within 8% for 47(94%) C3 (p=0.730) and 46(92%) C4 (p=0.964) levels. Kappa coefficient value was 0.90 for C3, indicating near-perfect agreement, and it was 1.0 for C4, indicating perfect agreement. C3 and C4 levels did not differ significantly between samples stored at 2-8°C and -40°C (C3: mean difference 0.01 g/L; p=0.73; C4: mean difference 0.00 g/L; p=0.96). Values for complement proteins 3 and 4 were not significantly different for samples stored at 2-8°C or -40°C.
What is this review about? This review provides an overview of a medication called survodutide. Survodutide is not yet approved for use but is currently being tested to treat people living with obesity, as well as those living with MASH (metabolic dysfunction-associated steatohepatitis). Obesity is a long-term disease in which extra energy stored as fat by the body begins to have harmful effects on health. MASH is an advanced form of a condition commonly called "fatty liver disease", or MASLD (metabolic dysfunction-associated steatotic liver disease). MASLD causes abnormal amounts of fat to build up in the liver. Obesity and MASH are linked diseases. Both involve problems related to metabolism, that is, the way that the body uses and stores energy. People living with obesity and those living with MASH often have other related health conditions at the same time. Improvements in dietary nutrition and increased physical activity are recommended treatments for people living with obesity and MASH. However, interventions such as medication and bariatric surgery are also effective treatments for metabolic dysfunction for those living with these diseases. Such therapies can help people reach their health goals. This review provides an overview of how survodutide works to help treat obesity and MASH. It also describes the key improvements in health status and the side effects experienced by people who took survodutide in clinical trials.
Traumatic dental injuries (TDIs) represent an important public health problem, and immediate access to accurate information is critical for their effective management. With the growing use of smartphones, mobile applications may serve as accessible tools for providing guidance during dental emergencies. This study aimed to evaluate the content and quality of smartphone applications available for the management of TDIs. A systematic search was performed in the Google Play Store and Apple App Store using relevant keywords related to dental trauma and dental emergencies. Applications providing information on the management or prevention of TDIs were included. The quality and content of the applications were assessed using the Mobile Application Rating Scale (MARS) and recommendations from the International Association of Dental Traumatology guidelines. Out of 124 identified applications, seven met the inclusion criteria (four iOS and three Android). All applications were free and mainly targeted patients. Most apps focused on the management of traumatic injuries to permanent teeth and provided guidance for various dental trauma emergencies. Among the evaluated applications, ToothSOS demonstrated the highest quality scores and the greatest adherence to IADT guidelines. Smartphone applications related to dental trauma management show variability in their content and educational value. Among the available applications, ToothSOS was identified as the most comprehensive and reliable resource for managing traumatic dental injuries.
Penile prosthesis surgery (PPS) has advanced significantly over the past decade with a wealth of research published, yet the key studies shaping contemporary clinical practice remain unclear. To identify and analyze the 50 most-cited primary research articles on PPS, published between 2014 and 2024, examining bibliometric characteristics, authorship networks, and thematic trends. A bibliometric analysis using the Web of Science Core Collection identified the most-cited PPS research articles within the study period. Data were extracted, stored, and analyzed using Microsoft Excel. VOSviewer (v1.8) generated authorship networks and keyword co-occurrence maps to visualize collaborations and thematic clusters. Bibliometric data on authorship, year, journal, study design, level of evidence, and keywords were extracted, stored, and analyzed. The 50 most-cited articles accrued 2283 citations (median 39). The most-cited study, by MS Gross, received 128 citations. MS Gross also authored the most first author publications (n = 3). Most studies were observational in nature. Over half were published in The Journal of Sexual Medicine (n = 26), followed by The Journal of Urology (n = 7), Urology (n = 5), and BJU International (n = 5). Thematic analysis identified dominant focuses: surgical outcomes (n = 27), complications (n = 26), devices (n = 17), infection (n = 16), special populations such as transgender or post-radical prostatectomy patients (n = 12), surgical techniques (n = 12), and predictors/risk factors (n = 7). This bibliometric analysis identifies the research domains shaping contemporary PPS, while highlighting a predominance of retrospective, U.S.-centered evidence and the need for future international, coordinated, prospective multicenter research to advance the field. This study benefits from a transparent methodology and validated bibliometric tools. Limitations include the use of a single database, reliance on citation metrics, dominance of high-volume centers, and the absence of altmetric analysis, which may restrict assessment of quality, generalizability, and contemporary research impact. This bibliometric analysis highlights the most influential PPS publications over the past decade. A concentration of output from U.S.-based authors and high-volume centers, as well as a tendency toward observational designs, underscores the current research landscape. Future work with thematic and geographic diversity as well as prospective and multicenter studies may further advance the field.
Carbon stocks and stock changes in harvested wood products (HWPs) are an important part of land sector greenhouse gas (GHG) estimation and reporting. HWPs broadly categorized as products in-use (e.g., solid wood and paper products) and in solid waste disposal sites (SWDS; e.g., landfills), store carbon transferred from harvested trees. In the United States (US), estimates of carbon in HWPs have historically been reported in the US GHG Inventory and included in submissions to the United Nations Framework Convention on Climate Change. These data have been obtained from national and international statistics on production and consumption of forest products and incorporated into a compilation system to estimate carbon in products in-use and in SWDS. In contrast, estimates of carbon in forest ecosystems have been obtained from nationwide forest inventory (NFI) data collected and maintained by the US Forest Service, Forest Inventory and Analysis (FIA) program. Here we describe a case study for the northern Lake States region of the US (Michigan, Minnesota, Wisconsin) where harvest data from the FIA program were integrated into HWP compilation systems. This advance improves consistency and continuity with forest ecosystem from NFI plots with estimates of HWPs. Over the 1900-2024 time period, total estimated net accumulation (i.e., balance of additions from transfers of harvested wood from forest ecosystems and losses from decay of wood harvested in the past) of carbon stored in products in-use was 277.0 ± 17.5 Million Metric Tons (MMT) Carbon (C) and in SWDS was 155.2 ± 9.8 MMT C. We estimate that HWPs from the region represent a carbon sink of 4.9 ± 0.1 MMT C in 2024. These estimates include HWPs produced in the region and exported domestically or internationally, as well as any HWPs produced and retained in the region, but not imports. The proposed methodology enables disaggregation with coarse national and state-level FIA data, and allows for integration of more specific, entity-level data to improve precision and reduce uncertainty in HWPs estimates in the US and improves consistency and continuity with forest ecosystem estimates across spatial and temporal scales.
Unstable angina (UA) represents a critical condition within the broader context of acute coronary syndromes, characterized by episodes of sudden chest pain resulting from insufficient blood flow to the myocardium. The pathophysiological mechanisms underlying UA remain complex and poorly understood, necessitating further investigation into the metabolic alterations associated with this condition. Identifying specific biomarkers for UA is crucial for improving diagnostic accuracy and facilitating timely therapeutic interventions. The present study was designed to elucidate the metabolic profile of UA by enrolling 60 patients diagnosed with UA, alongside 60 healthy controls. Participants were stratified into discovery and validation cohorts, with each group comprising 30 UA patients and 30 controls. The diagnosis of UA was performed in accordance with the 2020 European Society of Cardiology guidelines and the 2019 Chinese clinical pathway for UA management. Blood samples were meticulously collected following an overnight fast, processed, and subsequently stored at -80 °C. A comprehensive lipidomic analysis was executed utilizing ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), with compound identification referenced from the Metware Database. Data analysis involved advanced multivariate statistical techniques, including principal component analysis and orthogonal partial least squares-discriminant analysis. The analysis revealed significant metabolic discrepancies between the UA and control groups, identifying a total of 193 differential metabolites, of which 67 were notably upregulated in the UA cohort. Pathway enrichment analysis highlighted critical alterations in glycerophospholipid metabolism and necroptosis pathways. Furthermore, the application of machine learning algorithms, specifically neural networks and random forests, enabled the identification of key metabolic biomarkers, including TxB3, LPC(16:0/0:0), and DL-Carnitine, which exhibited robust diagnostic potential. In summary, our findings indicate that these metabolites may serve as promising candidate diagnostic biomarkers for UA, providing valuable insights into its pathophysiology.
Boreal forests are critical carbon sinks increasingly threatened by climate change. More than two-thirds of this boreal carbon is stored in soil and litter, highlighting the crucial role of litterfall for carbon and nutrient cycling. Boreal forests have stands of different plant functional types (deciduous, evergreen, and mixed), and we lack information on their contributions to litterfall production. This hinders our understanding of spatiotemporal variations in boreal litterfall production, and thus predictions under future climate scenarios. Here, we synthesized boreal litterfall data from published studies and applied generalized additive models to (1) examine stand age- and temperature-related litterfall dynamics across plant functional types and (2) project future trends under climate change, using two climate scenarios [CMIP6 climate scenarios (SSP2-4.5 and SSP5-8.5)]. Mean litterfall production was 1959 kg ha-1 year-1, with deciduous forests showing the greatest litterfall production. Litterfall production increased with stand age, then declined, peaking at 60 years for evergreen forests and 150 years for mixed forests. Deciduous forests showed no significant age-related trends in litterfall. Critical temperatures may affect litterfall production; for evergreen forests, the threshold is 5°C, above which litterfall production stabilized, with no threshold for deciduous nor mixed forests. The two CMIP6 climate scenarios predicted widespread declines in boreal litterfall production by the end of the 21st century. The decline in litterfall production was pronounced under SSP5-8.5, with 70% of boreal forests projected to experience litterfall declines exceeding -20%. Synthesis: Our study highlights the importance of incorporating specific plant functional types and stand age dynamics in predictive models of litterfall production. The findings provide a robust foundation for predicting future changes in boreal litterfall production, thereby advancing the understanding of vegetation-climate interactions in these forest ecosystems.
Strawberries (Fragaria × ananassa) are highly perishable due to their delicate texture, high respiration rate, and susceptibility to microbial spoilage. This study evaluated the effects of edible coatings chitosan (CH), Aloe vera gel (AVG), and coconut oil (CO), applied individually and in combinations, on postharvest quality of strawberries stored under ambient conditions (26°C ± 2°C; 65%-70% RH). Among all treatments, CH + AVG was the most effective, reducing weight loss by 37.98%, preserving firmness by 91.58%, and lowering total plate count by 44.98% compared to the control. This combination also better maintained pH, titratable acidity, TSS, color, phenolic content, and antioxidant activity. AVG alone effectively reduced weight loss and firmness loss, while CH better suppressed microbial growth. CO alone showed limited efficacy but improved when combined with CH or AVG. Overall, uncoated strawberries retained quality for 2 days, whereas CH + AVG extended shelf life to 4 days under ambient storage conditions.
The National Danish Injury Cohort (NDIC) is a nationwide, register-based cohort established to examine the incidence of total and specific injuries in Denmark and to provide insights into causes and consequences. Comprehensive individual-level information for this cohort is stored in the NDIC dataset, serving as a foundation for analyses of injury determinants and supporting the planning and evaluation of preventive measures aimed at reducing injury-related harm. Individuals registered in the Danish National Patient Register with an injury from 2010 onwards are included in the dataset. Additionally, it comprises persons in the Cause of Death Register whose deaths was attributed to accidents, violence, or suicide. The cohort is currently updated through 2022 and contains information on more than 7.2 million primary injury contacts and 26 thousand accident-related deaths. Analyses based on NDIC demonstrated substantial demographic and geographical disparities in the incidence rates of injuries. Overall, men exhibited higher rates of both injury incidents and injury‑related mortality compared with women. Marked differences were observed when stratifying by sex and age, as well as by region of residence. NDIC offers a solid data foundation facilitating research into injury trends, causes, and impacts, including disparities across social groups and geographic areas. It presents unique opportunities to explore novel research ideas to boost injury prevention, improve targeting of interventions, and reduce health inequalities. Strengthening this research area will help further reinforce NDIC's role in injury surveillance and evidence‑based policymaking.
In real-world clinical and biomedical settings, data distributions continuously evolve as new cases emerge in limited numbers. Traditional neural networks typically suffer severe knowledge forgetting when adapting to new classes unless retrained from scratch, which demands substantial resources. Moreover, biomedical datasets commonly exhibit imbalanced or long-tailed distributions where newly emerging classes have fewer samples, leading to classification bias toward established classes. However, the biomedical field currently lacks effective class-incremental learning methods to address this challenge of recognizing new diseases while preserving knowledge of previously learned ones. To address this gap, we introduce the first class-incremental learning method specifically designed for limited biomedical samples, featuring three key innovations: 1) a fine-grained semantic expansion module that employs diverse augmentation techniques to create compact feature distributions while accommodating new class generalization; 2) a cumulative entropy-based selection module that identifies and stores highly informative samples as exemplars for model review; and 3) a dynamic cosine classifier that mitigates classification bias from imbalanced datasets. Experiments across three datasets with different resolutions demonstrate superior performance under both imbalanced and long-tailed distributions, achieving up to 36.52% accuracy improvement over state-of-the-art methods.
Lipid droplets (LDs), intracellular organelles characterized by a phospholipid monolayer shell enclosing a neutral lipid core, serve as ideal reservoirs for lipophilic drugs. By exploiting the β-oxidation pathway, lipids stored in LDs can be transported to mitochondria, enabling targeted drug delivery. Notably, by altering the culture conditions, the particle size of LDs within cells can be regulated, demonstrating their suitability for development as drug carriers. Curcumin (CUR), a natural lipophilic photosensitizer, exhibits considerable potential for applications in photodynamic therapy (PDT). We confirmed that exogenous LDs can be taken up by cells and effectively localized around mitochondria. Then we exploited LDs as drug carriers to develop curcumin-loaded LDs (CUR-LDs) that capitalize on the intrinsic interplay between LDs and mitochondria to enable targeted mitochondrial delivery for photodynamic therapy. In vitro, CUR-LDs irradiated with 450 nm light (100 mW/cm2, 5 min) significantly increased intracellular reactive oxygen species (ROS) levels (5.2-fold), together with inactivation of mitochondrial cytochrome oxidase and reduced mitochondrial membrane potential (JC-1 red/green ratio: from 26.50 ± 4.81 to 1.76 ± 0.04), and ultimately promoted apoptotic cell death. These results highlight LDs as promising mitochondria-targeted drug carriers and demonstrate an effective curcumin formulation with potential applications in cancer therapy.
To obtain comprehensive insight into metabolic changes in potato seed tubers during storage and to identify patterns associated with physiological ageing, we analysed tuber metabolite composition using untargeted metabolomics based on gas and liquid chromatography-mass spectrometry (GC-MS and LC-MS). During two seasons, seed tubers of four contrasting cultivars (Agria, Festien, Innovator, and Lady Claire) were produced in a single field and after harvest, stored at different temperatures. During storage, the number of detected secondary metabolites increased progressively, particularly at higher temperatures (7-17 ˚C). Principal component analysis (PCA) revealed clear cultivar-specific metabolic profiles, with the starch cultivar Festien distinctly separated from the consumption cultivars, primarily caused by different amino acid composition. PCA further highlighted the impact of cold storage (4 ˚C) on primary metabolism, especially the accumulation of reducing sugars, as well as the combined effects of storage duration and elevated temperature on secondary metabolites, notably glycoalkaloids. Factor analysis (FA) supported these findings, with most metabolites strongly associated with the factor distinguishing cv. Festien from the other cultivars. Additionally, the leading factors captured cultivar-specific patterns and diverse trajectories reflecting the effects of storage duration and temperature. Together, these results provide a comprehensive overview of metabolic dynamics during storage and contribute to understanding the functional roles of metabolites in tuber physiological ageing. The online version contains supplementary material available at 10.1007/s11540-026-10083-2.
Serious adverse drug reactions, including anaphylaxis and hypersensitivity reactions to proton pump inhibitors (PPIs), have been reported and are expected to rise as a result of their widespread use and over-the-counter availability. Relevant physicochemical stability information of PPIs for use in drug hypersensitivity evaluation is virtually unavailable. Appropriate shelf life determination of PPIs for skin testing will improve patient safety and streamline allergy testing procedures. We studied the physicochemical stability of PPIs in plastic syringes. PPIs' chemical stability was determined as a function of percentage of initial concentration remaining by a validated stability-indicating high-performance liquid chromatography method. Physical stability was monitored for the presence of precipitation, haziness, and color change by visible spectrophotometry and pH shift. At refrigerated temperature, esomeprazole and omeprazole at 40 mg/mL and 4 mg/mL were stable for up to 7 days, while pantoprazole was stable for 7 and 2 days at 40 mg/mL and 4 mg/mL, respectively. At room temperature, esomeprazole and omeprazole at 40 mg/mL and 4 mg/mL, and pantoprazole at 4 mg/mL were stable for up to 2 days. Rabeprazole 20 mg/mL and 2 mg/mL were unstable at room temperature. Aseptically prepared 40 mg/mL and 4 mg/mL esomeprazole and omeprazole, and 40 mg/mL pantoprazole have a maximum shelf life of 7 days when stored at 2°C to 8°C. At room temperature, aseptically prepared 40 mg/mL and 4 mg/mL esomeprazole and omeprazole, and 4 mg/mL pantoprazole can be used within 2 days of preparation, while 20 mg/mL and 2 mg/mL rabeprazole should be prepared fresh and used within 24 hours.