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Article
Biology and Life Sciences
Animal Science, Veterinary Science and Zoology

Ali Kiani

,

German Jurgens

,

Gemma Gonzalez Ortiz

,

Carrie L. Walk

,

Teemu Rinttilä

Abstract: The impact of dietary inert digestibility markers on gut microbiota and intestinal fermentation remains poorly understood. This study investigated the effects of titanium dioxide (TiO₂) supplementation at 4 kg/ton feed, representing a typical dose used in animal nutrition studies, on fermentation dynamics and microbial composition in broiler chickens using combined ex vivo and in vivo approaches. Ex vivo fermentations were conducted using ileal and caecal microbiota and substrates collected from 32-day-old broiler chickens, with direct TiO₂ supplementation, with gas production and volatile fatty acid (VFA) profiles as main measurements. In parallel, 392 broiler chickens were fed diets with or without TiO₂ for 32 days, and ileal and caecal digesta were analysed for fermentation end-products and microbial composition using shotgun metagenomic sequencing. A second ex vivo experiment was performed using microbiota adapted to dietary TiO₂. In the first ex vivo model, TiO₂ reduced gas production and acetic acid concentration in the ileum (p < 0.05), whereas in the caecum it increased gas production, total eubacterial counts, and branched-chain fatty acids (BCFA) (p < 0.05). In vivo, TiO₂ did not affect growth performance or organ development but significantly increased isobutyric acid and total BCFA concentrations in the caecum (p < 0.05). Metagenomic analysis revealed increased caecal alpha diversity (Shannon index) and enrichment of taxa associated with amino acid metabolism, including Massilicoli timonensis, Blautia merdavium, Rubneribacter badeniensis, and Mediterraneibacter caccavium. The second ex vivo experiment showed similar trends, with increased gas and BCFA production. Collectively, these findings indicate that TiO₂ can modulate intestinal fermentation and microbial composition in a segment-specific manner, suggesting that dietary markers may not be biologically inert.

Article
Biology and Life Sciences
Anatomy and Physiology

Beate Rassler

,

Charly Bambor

,

Sarah Daunheimer

,

Coralie Raffort

,

Aida Salameh

Abstract: Previous studies on rats showed a deterioration of left ventricular (LV) function and myocardial injury characterized by oxidative/nitrosative stress, PARylation, and apoptosis in the heart after three days of hypoxia. In the present study on rats, we investigated whether a three-day recovery period in normoxia can reverse myocardial injury and dysfunction. Further, we studied the effects of norepinephrine (NE) administration as a model of strong sympathetic activation on hypoxia-induced LV dysfunction and myocardial damage, as well as their reversibility. Three days of normobaric hypoxia (10% O2) significantly decreased LV systolic function. Contrary to our expectations, NE infusion even aggravated the depression in LV function. These dysfunctions were completely reversed after three days of normoxic recovery. In contrast, nitrotyrosine as a marker of oxidative/nitrosative stress receded only partially, and poly-ADP-ribose (PAR) increased even further during the recovery period. Apoptosis-inducing factor receded at least partially indicating that PAR-related apoptosis (parthanatos) is not a major cause of hypoxia-induced LV dysfunction. Additional administration of NE mildly aggravated oxidative/nitrosative stress but did not significantly intensify PARylation and consequently, parthanatos. The findings demonstrate that hypoxia-induced LV dysfunction is reversible suggesting that subchronic hypoxia and subsequent reoxygenation has a better prognosis for the LV than classical ischemia/reperfusion injury.

Article
Biology and Life Sciences
Aging

Keisuke Kakazu

,

Ryoji Yoshimura

,

Atsushi Fukunari

,

Madoka Kumai

,

Akira Tsujimura

,

Hiromitsu Tanaka

Abstract: 1) Background: Coumestrol is a bioactive compound that inhibits HASPIN activity and prevents tau and H3 phosphorylation. Oral ingestion of CBSs increases blood testosterone levels, which decline with age causing late-onset hypogonadism. Oral ingestion of coumestrol-rich bean sprouts (CBSs) has been shown to suppress the onset of Alzheimer’s disease in 5xFAD mice and the onset of colon cancer in APCmin/+ mice. 2) Methods: We investigated the effect of oral ingestion of CBSs on the progression of aging in male senescence-accelerated prone 1 (SAMP1) mice allowed voluntary exercise or no exercise. The SAMP1 mice were divided into two groups fed either a standard diet or a diet including bean sprouts from 12 to 18 weeks of age. Each group was divided into two groups with voluntary exercise or no exercise. 3) Results: Voluntary exercise accelerated aging-related declines in blood testosterone levels, nerve growth factor levels, and spatial working memory, and oral ingestion of CBSs suppressed these age-related phenotypes, regardless of exercise. 4) Conclusion: Ingestion of CBSs prevented aging-related phenotypes in the experimental mice. A detailed analysis of the molecular mechanisms of coumestrol will be useful for understanding aging and preventing age-related diseases such as cancer, Alzheimer’s disease, and LOH.

Article
Biology and Life Sciences
Food Science and Technology

Mio Matsuoka

,

Hiroko Shimaya

,

Yoshihito Iwanami

,

Shohei Iijima

Abstract: Background/Objectives: The semi-solid enteral nutrition method, in which semi-solid nutrients are administered through a gastrostoma rather than liquid nutrients, is a medical technology for nutritional management developed in Japan. This nutritional method has spread rapidly, and in 2018, the Home Semi-solid Enteral Nutrition Guidance and Management fee was newly established in the payment system for medical services. However, there are few studies evaluating this nutrition method in actual clinical practice. Methods: Using the DeSC medical claims database, we investigated patient characteristics, the number of fee calculations, and the length of hospital stay for all hospitalizations and for pneumonia during and after fee calculation. Results: Home semi-solid enteral nutrition guidance and management was received at least once by 3105 patients (mean age: 79.4 years). Cerebrovascular disease, nervous system disease, dementia, and pneumonia were the most common diseases at the start of guidance and management, and the mean number of sessions received was 7.7. The mean length of stay for any hospitalization was significantly shorter during the guidance and management period than after the last guidance and management session (8.2 vs. 29.1 days). Notably, the mean length of hospital stay for pneumonia was also significantly shorter during the guidance and management period than after the last guidance and management session (3.1 vs. 10.2 days). Conclusions: This study clarified the clinical status and outcomes of patients who received Home Semi-solid Enteral Nutrition Guidance and Management. The results suggested that application of the semi-solid enteral nutrition method can contribute to stable patient home care.

Article
Biology and Life Sciences
Animal Science, Veterinary Science and Zoology

Mohd Yasir Khan

,

Farah Maarfi

,

Abid Ullah Shah

,

Nithyadevi Duraisamy

,

Mohammed Cherkaoui

,

Maged Gomaa Hemida

Abstract: Background. The main protease (Mpro/3CLpro) of coronaviruses (CoVs) is an essential enzyme involved in viral replication and represents an attractive target for antiviral drug discovery. Based on the similar binding pocket residues within the Mpro of different CoVs, the study aimed to identify potential inhibitors of Mpro from PDB ID 6M2N, using inte-grated computational approaches. Methods. Structure-based pharmacophore modeling, virtual screening, molecular docking, MM-GBSA binding energy calculation, and molecu-lar dynamics (MD) simulation were performed using BIOVIA Discovery Studio. The vali-dated pharmacophore model was utilized to screen the ZINC database, followed by dock-ing and 100 ns MD simulation analyses of the top-ranked compounds. Results. The pharmacophore model 01 demonstrated favourable predictive performance (AUC = 0.781). Virtual screening identified 483 compounds, from which 21 compounds were selected for docking studies. Among them, ZINC95473654 (Lig-1), ZINC95473725 (Lig-2), and ZINC08792368 (Lig-3) exhibited strong binding affinity toward Mpro. Lig-1 demonstrated the best docking score and binding free energy along with stable interactions with key cat-alytic residues HIS41, CYS145, and GLU166. MD simulation analyses further confirmed that Lig-1 and Lig-2 maintained stable conformations and persistent intermolecular inter-actions throughout the 100 ns simulation period. Conclusion. The findings suggest that Lig-1, followed by Lig-2, may serve as promising CoVs Mpro inhibitors and warrant fur-ther experimental validation. Further experimental validation are required to consolidate the identified compounds as universal inhibitors of the CoVs-Mpro enzyme.

Article
Biology and Life Sciences
Immunology and Microbiology

Josh Walker

,

Akila Rekima

,

Andreea Cornelia Udrea

,

Katrine Bie Larsen

,

Adrian Schwarzenberg

,

Steffen Yde Bak

,

Niels Christensen

,

Svetlana Gerdes

,

Weiqing Zeng

,

Ashley Hibberd

+1 authors

Abstract: Effective canine gastrointestinal health depends on suppression of enteric pathogens and maintenance of epithelial barrier integrity. Limosilactobacillus reuteri ATCC PTA 6127 (Lr6127) is a dog‑derived probiotic, but evidence supporting its protective capacity remains limited. Here, we evaluated the antimicrobial and epithelial‑supportive effects of Lr6127 using a canine epithelial cell model. Cell‑free supernatant (CFS) from Lr6127 significantly inhibited the growth of canine‑relevant pathogens, including Escherichia coli (52.0 ± 1.3%), Clostridium perfringens (54.0 ± 2.7%), and Salmonella typhimurium (48.6 ± 1.2%), compared with the medium control (P <  0.0001). Pathogen inhibition increased in a dose‑dependent manner with increasing CFS concentrations. Untargeted metabolomic analysis revealed enrichment of multiple antimicrobial‑associated metabolites, indicating multi‑component pathogen suppression, with genomic analysis supporting the aromatic amino acid–derived metabolite findings. In addition, viable Lr6127 significantly reduced epithelial adhesion of all tested pathogens (P <  0.01). Beyond direct antimicrobial effects, Lr6127 CFS promoted epithelial wound healing at later time points, accompanied by coordinated modulation of proteins associated with cytoskeletal remodeling and barrier repair. Collectively, these findings suggest that Lr6127 is associated with pathogen suppression, reduced adhesion, and epithelial wound repair mechanisms.

Article
Biology and Life Sciences
Animal Science, Veterinary Science and Zoology

Yuyang Fan

,

Ge Gao

,

Xinyue Jiang

,

Dongxu Ming

,

Yanpin Li

,

Wenjuan Sun

,

Xilong Li

,

Yu Pi

Abstract: The objective of this study was to evaluate the effects of partially replacing wheat bran with poplar wood composite fiber (PWCF) on growth performance, immune status, apparent total tract digestibility (ATTD), and gut microbial composition in growing pigs. A total of 140 healthy crossbred (Duroc × Landrace × Yorkshire) growing pigs with an initial body weight of 47.25 ± 0.49 kg were randomly assigned to two dietary treatments, with five replicates per treatment and fourteen pigs per replicate. The control (CT) group was fed a corn–soybean meal–based diet, whereas the experimental group re-ceived the same diet in which 2% wheat bran was replaced by PWCF. The experiment lasted for 60 days. Compared with the CT group, replacing wheat bran with PWCF did not affect body weight, average daily feed intake, feed conversion ratio, or average daily gain on days 30 or 60 (P > 0.05). In addition, no negative effects were observed on ATTD of nutrients and serum immunoglobulin A (IgA), IgG, and IgM levels at either time point, indicating that PWCF can serve as a suitable partial substitute for wheat bran in growing pig diets. However, it could regulate nitrogen metabolism by reducing blood urea nitrogen (BUN) concentration and the BUN/creatinine ratio, as well as decreasing total free amino acids in serum (P < 0.05). In addition, the antioxidant capacity can be improved by increasing catalase activity. Gut microbiota analysis showed that the re-placement significantly increased the relative abundances of Treponema, Lachnospi-raceae_XPB1014_group, Prevotellaceae_UCG-001, Prevotellaceae_UCG-003, Prevotel-laceae_UCG-004, and norank_f_Oscillospiraceae (P < 0.05). These changes suggest that PWCF modulates gut microbiota and enriches fiber-degrading bacterial populations. Overall, substituting wheat bran with PWCF did not impair growth performance, im-munity, or digestibility, while altering microbial community composition. These find-ings support the potential application of PWCF as an alternative fiber source, contrib-uting to greater diversity in feed formulation.

Article
Biology and Life Sciences
Animal Science, Veterinary Science and Zoology

Soontaree Petchdee

,

Ying Xufeng

,

Suchada Huttayananont

,

Kotchapol Jaturanratsamee

,

Chattida Panprom

,

Wannisa Meepoo

,

Ratikorn Bootcha

Abstract: Transcatheter edge-to-edge repair (TEER) is a recent minimally invasive method of managing mitral regurgitation (MR) in dogs with myxomatous mitral valve disease (MMVD). The goal of interventions is to minimize MR severity. The objective of this study was to determine the association between reduced MR and changes in myocardial work indices after TEER in dogs. Client-owned dogs with moderate-to-severe MR were enrolled in the study. TEER performance was completed with multimodal imaging guidance in all 10 dogs. Before and after the procedure, myocardial work was analyzed. MR severity, transmitral pressure gradients, left atrial and ventricular measurements, and index of myocardial work (GWI, GCW, GWW, and GWE) were calculated. TEER significantly reduced MR severity in the majority of dogs. MR decrease was associated with a greater efficiency of myocardial work, more constructive work, and less wasted energy. No significant negative associations of moderate post-procedure gradients with short-term clinical outcomes emerged. TEER-mediated reduction of MR improves myocardial function in dogs. However, long-term studies are also needed to examine the effects of residual MR and transmitral gradients on cardiac function and clinical outcome.

Article
Biology and Life Sciences
Animal Science, Veterinary Science and Zoology

Andreea Cornelia Udrea

,

Katrine Bie Larsen

,

Steffen Yde Bak

,

Niels Christensen

,

Adrian Schwarzenberg

,

Akila Rekima

,

Ashley Hibberd

,

Chong Shen

Abstract: Coordinated responses of intestinal epithelial and immune cells are essential for maintaining barrier integrity and immune homeostasis in dogs, yet mechanistic understanding of probiotic‑derived metabolites remains limited due to reliance on non‑canine experimental models. Here, we investigated metabolites derived from Limosilactobacillus reuteri strain ATCC PTA6127 (Lr6127), delivered as cell-free supernatants (CFS), using canine epithelial MCA-B1 cells and macrophage-like DH82 cells subjected to lipopolysaccharide (LPS)–induced inflammatory stress. Lr6127 CFS significantly reduced epithelial permeability, decreasing FITC‑dextran leakage to 94.9 ± 1.9% relative to LPS-treated controls normalized to 100% (P < 0.001), despite no detectable transcriptional changes in tight junction, adherent junction, or mucin genes. Barrier effects were instead associated with changes in markers of cellular stress re-sponses, with heme oxygenase expression reduced from 0.9 ± 0.1 to 0.7 ± 0.1 (P < 0.05). In DH82 immune cells, Lr6127-derived metabolites suppressed LPS-induced stress and inflammatory signaling, enhanced anti-apoptotic responses as reflected by increased BCL2 expression (1.4 ± 0.1 vs. 1.0 ± 0.0; P < 0.01) and elevated BCL2/BAX ratios (P < 0.01), and reduced pro-inflammatory mediators including IL-6 and CCL2 (P < 0.05–0.001). Proteomic analysis corroborated reduced abundance of inflammatory and STAT-associated signaling proteins under LPS challenge while promoting immune readiness under resting conditions. Collectively, these results suggest that Lr6127‑derived metabolites may support epithelial barrier integrity and immune re-balancing potentially through modulation of cellular stress and inflammatory path-ways.

Concept Paper
Biology and Life Sciences
Aging

Peter Carey

Abstract: Dementia represents a growing global public health challenge, driving the rapid expansion of educational interventions aimed at improving awareness and promoting risk-reduction behaviours. Despite this growth, existing research demonstrates a persistent gap between knowledge acquisition and meaningful behavioural change. This paper presents a realist-informed conceptual analysis and proposes an integrative conceptual framework for evaluating the real-world effectiveness of digital dementia education. Integrating health literacy theory, the Capability–Opportunity–Motivation Behaviour (COM-B) model, and implementation science, the framework conceptualises dementia education as a dynamic, multi-component process involving resource availability, user engagement, interpretative engagement, behavioural readiness, contextual influences, and real-world outcomes. Particular emphasis is placed on interpretative engagement, grounded in constructivist and sensemaking perspectives, as a key mechanism linking exposure to educational content with behavioural intention and action. The paper identifies critical limitations in current evaluation approaches, including overreliance on knowledge-based outcomes and insufficient consideration of contextual, emotional, and implementation influences. By advancing a user-centred and context-sensitive framework, this study contributes to the development of more theoretically informed and implementation-oriented approaches for evaluating digital dementia risk-reduction education, particularly among midlife populations.

Review
Biology and Life Sciences
Immunology and Microbiology

Monthon Lertcanawanichakul

,

Attarat Pattanawongsa

,

Sueptrakool Wisessombat

Abstract: Endophytic fungi are microorganisms that reside asymptomatically within healthy plant tissues and establish complex symbiotic relationships with their host plants. In recent years, these microorganisms have gained increasing attention due to their remarkable ability to produce diverse secondary metabolites with significant biological and pharmacological activities. Numerous studies have demonstrated that endophytic fungi isolated from medicinal plants can synthesize bioactive compounds exhibiting antioxidant, antimicrobial, antiviral, anti-inflammatory, antidiabetic, and anticancer properties. Interestingly, some endophytes are capable of producing metabolites structurally similar or identical to those found in their host plants, including taxol, camptothecin, and various phenolic compounds. Compared with conventional plant extraction, endophytic fungi offer several advantages such as rapid growth, sustainable production, reduced environmental impact, and the potential for large-scale fermentation. These characteristics make endophytes promising alternative sources of natural products for pharmaceutical, cosmetic, agricultural, and industrial applications. This review summarizes the biological characteristics of endophytic fungi, methods for isolation and identification, and the major classes of bioactive compounds derived from fungal endophytes, with emphasis on their pharmacological significance and future biotechnological potential.

Review
Biology and Life Sciences
Plant Sciences

Delia Maria Luca

,

Marius-Nicuşor Grigore

,

Oscar Vicente

Abstract: Climate change is placing global agriculture under growing pressure, as plants must withstand extreme environmental conditions such as drought and high salinity, both inducing osmotic and oxidative stress. As part of their survival strategies, plants accumulate protective molecules (osmolytes), including the amino acid proline. For decades, plant biology has largely assumed that high proline accumulation under stress signals strong stress tolerance. However, this review challenges that “proline-centric” perspective. Analyses across a wide range of plant species reveal a more complex picture. Stress-induced proline accumulation is not universal: in some species, proline levels remain relatively unchanged, with other metabolites acting as functional osmolytes, or increase only in response to artificially applied severe stress conditions. Even when proline increases, its absolute concentrations may be too low to contribute significantly to osmotic adjustment. Nevertheless, proline may still be involved in stress tolerance mechanisms through its additional roles, detoxifying reactive oxygen species (ROS), directly stabilising proteins or acting as a stress signalling molecule. Comparative analyses of genetically related taxa with varying degrees of stress tolerance sometimes show negative correlations between proline accumulation and tolerance, with higher proline concentrations measured in the most sensitive genotypes. Overall, the evidence indicates that proline’s role in plant survival is highly context-dependent and strongly influenced by genetic background and must therefore be evaluated on a case-by-case basis. Distinguishing whether proline acts as an adaptive defence or merely as a biochemical marker of physiological strain is essential for accurately assessing plant stress tolerance.

Article
Biology and Life Sciences
Neuroscience and Neurology

Da-un Jung

,

Ahreum Lee

,

Dalnim Kim

,

Hyun-Jeong Yang

Abstract: Neuroinflammation, driven by microglial activation and oxidative stress, is a key pathological feature of various neurodegenerative diseases. Dendropanax morbifera Léveille (DM) is a medicinal plant known for its diverse pharmacological activities; how-ever, the influence of leaf developmental stage on its neuroprotective potential remains poorly understood. In this study, we compared the phytochemical profiles of young DM (YDM) and mature DM leaves and evaluated their effects on neuronal metabolism and microglia-mediated neuroinflammation. HPLC analysis revealed that YDM contained approximately 2.4-fold higher levels of chlorogenic acid than DM, while DM exhibited higher quercetin content. In differentiated N2A neuronal cells, YDM treatment significantly upregulated the expression of key metabolic and mitochondrial regulators, including PGC-1α, PPARγ, and CPT2, suggesting an enhanced capacity for mitochondrial biogenesis and fatty acid β-oxidation. Under inflammatory conditions, YDM more potently suppressed the secretion of pro-inflammatory cytokines (IL-6 and TNF-α) in LPS-stimulated BV2 microglia compared to DM. Further-more, in N2A cells treated with a BV2–conditioned medium, both extracts effectively mitigated reactive oxygen species production and restored brain-derived neurotrophic factor expression. These findings demonstrate that leaf age is a critical determinant of the phytochemical composition and biological activity of DM. Our results suggest that chlorogenic acid-rich YDM preparations may offer superior therapeutic advantages in targeting neuroinflammatory and metabolic dysregulation in the central nervous system.

Article
Biology and Life Sciences
Ecology, Evolution, Behavior and Systematics

Francesco Scarton

,

Mauro Bon

,

Roberto Valle

Abstract: Coastal lagoons are key wintering habitats for waders, yet long-term changes in their community structure remain poorly understood in Mediterranean systems. We analysed a 30-year dataset (1993–2022, excluding 2021) of wintering waders in the Venice Lagoon to assess trends in abundance, community structure, thermal composition and spatial patterns. Total abundance increased significantly (+3.5% yr⁻¹), while species richness ranged between 12–21 species per winter. Community structure changed markedly, with increasing dominance of a few species, particularly Dunlin, leading to reduced evenness. Species-level analyses showed a prevalence of increasing trends: nine of the 19 species analysed increased significantly, one declined, one was stable and eight showed uncer-tain trends. The Community Temperature Index (CTI) increased significantly (p = 0.001), suggesting a shift towards species with higher thermal affinities, but this pattern was not robust to the exclusion of Dunlin C. alpina, indicating dominance-driven dynamics. Spatial analyses revealed a strong increase in the open lagoon (p < 0.001) and a decline in fish farms (p = 0.008), indicating a shift towards natural tidal habitats. Overall, the assemblage is increasing but structurally simplified, highlighting the need to integrate species- and community-level approaches when interpreting ecological indicators.

Article
Biology and Life Sciences
Aging

Jon Stephen Yarbrough

,

Subramanya Pandruvada

,

William D. Hill

,

Hong Yu

Abstract: Old murine bone marrow-derived monocytes and macrophages (BMMs) display enhanced CD38 protein, a nicotinamide adenine dinucleotide (NAD+) glycohydrolase, and reduced NAD+ level after infection with oral pathogens compared with young controls. We aimed to determine whether treatment with a CD38-specific inhibitor (78c) in mice with experimental periodontitis could alleviate alveolar bone loss and enhance NAD+ levels in tissues compared with vehicle treatment. Twenty young (2-month-old) and twenty old (18-month-old) C57BL/6J mice with experimental periodontitis were treated with either vehicle or 78c twice daily via intraperitoneal injection for 4 weeks. The liver, spleen, and right maxillary tissues were harvested to analyze NAD+ levels. The left maxillary tissues were scanned by micro-CT, processed for tissue sectioning, and stained with hematoxylin and eosin (H&E) and tartrate-resistant acid phosphatase (TRAP). Treatment with 78c significantly enhanced NAD+ levels in the liver and spleen of both young and old mice, and significantly increased NAD+ in the right maxilla of old mice compared with vehicle treatment. Additionally, treatment with 78c alleviated alveolar bone loss in both young and old mice. Our results support the notion that 78c is a promising therapeutic strategy for treating periodontal disease associated with aging.

Article
Biology and Life Sciences
Life Sciences

Dias Permeisari

,

Dian Ermawati

Abstract: The sterility of injection pharmaceutical preparation is the most crucial requirement to achieve, as it is injected directly to human body, either intravenously, intramuscularly, or other injection routes and once drug is injected, it moves to other parts of the body through blood flow follows the rules of drug distribution and will have direct contact to all tissues and organ [1]. Theoretically, in order to prevent contamination of microbial by inhibiting the proliferation process, especially in multiple dose of injection drugs, in the final formulation of the drug may need special addition of suitable preservative agent in the preparation [2]. The first step to perform this experimental study was by preparing the sterile pharmaceutical preparation, Diphenhydramine Hydrochloride injection at Sterile Pharmaceutical Preparation Laboratory, of Universitas Muhammadiyah Malang, Indonesia. Once the injection drug was ready, the second step conducted sterility test. The most common method used for sterility test in injection drugs is named direct inoculation. It was conducted by preparing sample from diluted solution of the injection drug, and the concentration was divided into five groups of sample 1:1, 1:2, 1:3, 1:4, 1:5, and undiluted sample (with three times replications) has determined certain level of inactivation of benzyl alcohol as its preservative agent, that was undiluted sample in Thioglycolate medium and 1:1 in Casamino medium. The indicator of bacterial growth in the study was Bacillus subtilis for Thioglycolate medium on range of temperature 30°-35 °C, and Candida albicans as an indicator of fungal growth in Casamino medium on range of temperature 20°-25 °C, both of Thioglycolate and Casamino medium were observed for 14 days. Inactivation of preservative agent and sterility test were performed under LAFC condition and it required some controls of LAFC environment to ensure that experiment was conducted under optimum condition and to avoid false positive result. According to those results of our study, the sterility test has indicated that our Diphenhydramine Hydrochloride injection was sterile after over a period of 14 days of observation.

Review
Biology and Life Sciences
Life Sciences

Elizabeth Jones

,

Natalie Eppler

,

Forkan Ahamed

,

Yuxia Zhang

Abstract: Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide and remains therapeutically challenging owing to its marked inter- and intratumoral heterogeneity, diverse etiologies, and high rates of drug resistance. This review aims to summarize the current knowledge on the complexity of HCC and to evaluate emerging therapeutic strategies, with a particular focus on targeting the RNA-binding protein HuR as a novel approach to overcome treatment limitations. Methods: A narrative review was conducted of peer-reviewed publications focusing on HCC pathogenesis, tumor heterogeneity, resistance mechanisms, and therapeutic developments. Emphasis was placed on studies investigating the molecular drivers of HCC, tumor microenvironment interactions, and novel treatment strategies. Results: HCC progression is driven by complex interactions between genetic, epigenetic, and environmental factors, resulting in significant variability in treatment response. Tumor heterogeneity, cancer stem cell populations, and an immunosuppressive tumor microenvironment contribute to resistance to conventional therapies, including multikinase inhibitors and immune checkpoint inhibitors. Emerging strategies targeting these mechanisms, such as combination immunotherapies, metabolic targeting, and epigenetic modulation, show promise, but remain limited by incomplete efficacy. HuR is a central post-transcriptional regulator that stabilizes mRNAs encoding oncogenic and pro-survival factors. Preclinical studies have demonstrated that the pharmacological inhibition of HuR disrupts tumor-promoting pathways and enhances therapeutic sensitivity. Conclusions: The complexity of HCC necessitates multifaceted precision-based therapeutic approaches. Targeting HuR is a promising strategy for addressing tumor heterogeneity and drug resistance. Continued integration of molecular profiling, advanced technologies, and rational combination therapies is critical for translating these advances into improved clinical outcomes.

Article
Biology and Life Sciences
Life Sciences

Yuki Ueda

,

Shunsuke Hirabayashi

,

Satoshi Yamada

,

Sachiko Nakakubo

,

Midori Nakajima

,

Takeru Goto

,

Jutaro Abe

,

Yukayo Terashita

,

Atsushi Manabe

,

Torayuki Okuyama

+1 authors

Abstract: Enzyme replacement therapy (ERT) for central nervous system symptoms and newborn screening (NBS) are available in Japan for patients with mucopolysaccharidosis type II (MPS II). The participants were individuals referred to our facility through NBS who were suspected of having neuronopathic MPS II. We reviewed the clinical course of patients who received intracerebroventricular (ICV)-ERT, idursulfase beta (Hunterase®), followed by hematopoietic stem cell transplantation (HSCT) using umbilical cord blood. Longitudinal measurements of heparan sulfate (HS) in the cerebrospinal fluid (CSF) were performed as a therapeutic biomarker, and developmental age was evaluated. Three patients diagnosed and treated with ICV-ERT received cord blood transplantation (CBT). All patients achieved successful engraftment with no severe complications except for one patient with sinusoidal obstruction syndrome. The HS in the CSF showed a temporary increase during the ERT discontinuation period owing to CBT and a subsequent reduction after the resumption of ICV-ERT. The patients exhibited age-appropriate development. The pattern of change in HS suggests the importance of continuing ICV-ERT even after HSCT. The combination of ICV-ERT and CBT may yield promising outcomes in patients with neuronopathic MPS II and underscores the importance of early intervention through NBS.

Article
Biology and Life Sciences
Life Sciences

Kirill Nickolaevich Kornilov

Abstract: Production of a biodegradable, environmentally friendly polymer film material, composed of potato starch (PS), xanthan gum (XG), and plasticizers: glycerin, sorbitol, and citric acid, was carried out. The effect of these components on the structural and biopolymer composite mechanical properties, including elasticity and tensile strength, was investigated. The addition of XG significantly reduces the hardness for the film forming materials, thereby lowering the difficulty of gelatinization. It was demonstrated that increasing the plasticizers mass during composite blend preparation improved elasticity but reduced the mechanical strength of the films. It is assumed that these additives in the biopolymer disrupted hydrogen bonds and other intermolecular contacts between starch and gum macro chains. Glycerol influences the elasticity of the bioplastic, while sorbitol influences its strength. Taking various factors into account, the optimal combined concentration of glycerol, sorbitol and citric acid was determined in composite during film preparation. Based on the results of the new polymeric films’ flexibility study, it was concluded that they could be used as a replacement for traditional, non-biodegradable polymeric materials. At the optimal concentration of components, the strength of polymer films is 1.6 MPa, and the relative elongation is 45%.

Article
Biology and Life Sciences
Immunology and Microbiology

Wenya You

,

Mingyue Liu

,

Hongkuan Ji

,

Zixuan Zhao

,

Hao Li

,

Xiuling Wang

Abstract: Anaerobic bacteria are the dominant group in the animal intestinal microbiota, and most strains cannot grow or proliferate normally upon exposure to air. Blautia sp. AUH-JLD56 (KF374935) is a strictly anaerobic strain previously isolated by our research group from human feces. Under anaerobic conditions, this strain converts arctigenin to 3′-demethylarctigenin (3′-DMAG), reaching a maximum conversion concentration of 3.6 mM. To improve the oxygen tolerance of this wild-type strain, we performed long-term oxygen tolerance domestication and successfully obtained an oxygen-tolerant mutant. Phenotypic analysis showed that the growth of the oxygen-tolerant mutant under aerobic conditions (OD600 nm = 2.37) was slightly lower than that of the wild-type under strictly anaerobic conditions (OD600 nm = 2.82). Compared with the wild-type, the mutant exhibited an accelerated aerobic growth rate and enabled stable conversion of arctigenin. Notably, under aerobic conditions, the mutant achieved a maximum conversion concentration of 8.2 mM, which is significantly higher than the 3.6 mM obtained with the wild-type under anaerobic conditions. This study realizes, for the first time, efficient aerobic bioconversion of arctigenin to 3′-DMAG using an oxygen-tolerant derivative of a strict anaerobe, thereby overcoming the oxygen-dependent limitation of such strains. Our approach provides a new strategy and technical reference for the oxygen tolerance domestication and industrial application of other intestinal strict anaerobes with specific enzymatic functions.

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