Ruthenocenyl and 1-Adamantyl Paclitaxel Analogs Disrupt the Balance between βIII- and βIVa-Tubulin and Inhibit the Growth and Invasiveness of Colon Cancer.

Taxanes are widely used anticancer agents that stabilize microtubules and arrest cell division. However, their efficacy in colon cancer is limited by the chemoresistance associated with βIII-tubulin (TUBB3) upregulation. Herein, ferrocenyl, ruthenocenyl, and 1-adamantyl analogs of paclitaxel were synthesized and biologically evaluated.

The modified mRNA vaccine protects immunocompromised AG129 mice from lethal challenge and multi-tissue infection by Zika virus.

The multiple epidemics of Zika virus (ZIKV) posed a substantial threat to public health. Clinical evidence suggests that ZIKV could break through the blood-brain, blood-placenta, and blood-testis barriers, leading to severe outcomes such as congenital malformations in newborns and Guillain-Barré syndrome in adults. Currently, there are no specific treatments for ZIKV infection.

A fusion ORF3a-E subgenomic RNA involved in SARS-CoV-2 infection efficacy by influencing cellular protein synthesis.

Subgenomic RNAs (sgRNAs) are discontinuous transcription products of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that are involved in viral gene expression and replication, but their exact functions are still being studied. Here, we report the identification of a nested ORF3a-sgRNA, the fusion ORF3a-E-sgRNA, which is involved in the infection process of SARS-CoV-2. This sgRNA encodes both ORF3a and E and can be detected throughout the viral life cycle in SARS-CoV-2-infected cells with high copy numbers.

Multi-omics investigation of spontaneous T2DM macaque emphasizes gut microbiota could up-regulate the absorption of excess palmitic acid in the T2DM progression.

Although gut microbiota and lipid metabolites have been suggested to be closely associated with type 2 diabetes mellitus (T2DM), the interactions between gut microbiota, lipid metabolites, and the host in T2DM development remains unclear. Rhesus macaques may be the best animal model to investigate these relationships given their spontaneous development of T2DM. We identified eight spontaneous T2DM macaques and conducted a comprehensive study investigating the relationships using multi-omics sequencing technology.

A QS21+ CpG-Adjuvanted Rabies Virus G Subunit Vaccine Elicits Superior Humoral and Moderate Cellular Immunity.

Background: Rabies remains a fatal zoonotic disease caused by rabies virus (RABV), posing substantial global health challenges. Current vaccine production faces challenges in manufacturing efficiency and cost-effectiveness. The RABV glycoprotein (RABV-G) serves as the key antigen for eliciting protective immunity.

Systemic Inflammatory Burden Causes Liver Injury in H1N1-Infected Mice.

Clinical evidence has associated H1N1 influenza with liver impairment, yet the underlying mechanisms remain poorly understood. Here, we investigated H1N1-induced liver damage and its potential mechanisms using a BALB/c mouse infection model. Pathological examination and serum aspartate transaminase (AST) and alanine transaminase (ALT) were assessed.

Extracellular Vesicles Derived from Breast Cancer Cells: Emerging Biomarkers of Tumor Progression and Metastasis.

Breast cancer (BC) remains one of the most prevalent and life-threatening malignancies worldwide, marked by significant heterogeneity and complex mechanisms of progression. Despite major advances in understanding its molecular and cellular basis, the processes driving tumor progression and metastasis continue to challenge effective treatment. Among the emerging research areas, extracellular vesicles (EVs) have gained considerable attention for their key role in intercellular communication and their contribution to cancer biology.

Enhancement of immunogenicity of SARS-CoV-2 spike protein expressed in by fusion of the CRM197 functional domain.

As an immunogenic non-toxic mutant of diphtheria toxin (DT), cross-reacting material 197 (CRM197) exhibits a significant immunogenicity-enhancing effect on various pathogenic vaccines. However, its application in vaccines against highly pathogenic pathogens remains underexplored. In this study, we incorporated CRM197 into a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine, aiming to identify a molecular adjuvant capable of inducing broad-spectrum neutralizing antibodies and to develop a subunit vaccine with stronger cross-reactivity, improved safety, and greater accessibility.

Establishment and Characterization of Behavioral Changes in the Nuclear Localization Human α-Synuclein Transgenic Mice.

This study aimed to establish a transgenic mouse model expressing nucleus-localized human α-synuclein (α-syn) to investigate its impact on the central nervous system and behavior and the underlying mechanisms involved. A nuclear localization sequence (NLS) was added to the end of the human SNCA (hSNCA) gene. Subsequently, an empty vector and a mammalian lentiviral vector of the hSNCA-NLS were constructed.

Discovery of '-(1-(coumarin-3-yl)ethylidene)benzenesulfonohydrazide as a novel wound healing enhancer: synthesis, biological assessment, and molecular modeling.

Wound healing poses a considerable challenge in the domain of medical science. In modern clinical practice, there is a growing trend towards using herbal compounds to aid in the repair process. Among these, coumarin, a phytochemical recognized for its antibacterial and wound-healing properties, has attracted significant interest.

A preliminary bioinformatic screen to identify SRI SMC2 PSIP1 TLE4 and MSX1 as potential diagnostic and prognostic markers of osteoarthritis.

Osteoarthritis (OA) is the most common degenerative joint disease, leading to severe pain and functional disability for nearly 530 million people worldwide. OA is characterized by progressive loss of cartilage and synovial hyperplasia from the articulating surfaces of any diarthrodial joints, however, the majority of cases account for the hip and knee. Currently, regenerative therapy based on stem cells has emerged as one of the most promising and rapidly evolving strategies in OA.

Pearson syndrome with atypical presentation of short stature and atypical limb proportions - First reported case in Slovakia.

In this case report, we describe an individual with Pearson syndrome, representing the first reported case in Slovakia. The patient was 1.5-year-old boy with pancytopenia including macrocytic anemia, neutropenia and thrombocytopenia, pancreatic insufficiency, hepatopathy, psychomotor development delay, short stature and failure to thrive.

The Expression Pattern of the Splice Variants of Coxsackievirus and Adenovirus Receptor Impacts CV-B3-Induced Encephalitis and Myocarditis in Neonatal Mice.

Coxsackievirus B3 (CV-B3) infection causes inflammatory conditions such as viral myocarditis and meningitis, and incidence rates are rising annually. While children are more likely to be affected by severe manifestations, the molecular basis of this age-dependent susceptibility is poorly understood. In this study, we used young Balb/c mice at three developmental stages (7-, 14-, and 30-day-old mice) to investigate CV-B3 pathogenesis.

A Clinical Investigation Into the Effects of Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Vaccination in Children With Acute Lymphoblastic Leukemia.

This study systematically evaluated the humoral immune responses and cytokine profiles of 259 pediatric participants, comprising both healthy individuals and patients with Acute Lymphoblastic Leukemia (ALL), following either administration of an inactivated SARS-CoV-2 vaccine or natural infection. The data indicate that vaccination elicits measurable immune responses in both groups, supporting its relevance in immunocompromised pediatric populations. Although antigen-specific responses to the spike (S) protein and receptor-binding domain (RBD) were attenuated in the ALL cohort, levels of neutralizing antibodies and antibodies capable of inhibiting RBD-ACE2 binding were comparable to those in healthy controls, suggesting that functional antibody-mediated immunity can still be achieved in ALL patients.

Polymerase Chain Reaction-Based Diagnosis of Leishmaniasis Targeting Kinetoplast Minicircle DNA in Infants with Hemophagocytic Lymphohistiocytosis.

In this study, we aimed to assess the efficacy of polymerase chain reaction (PCR) targeting Leishmania kinetoplast minicircle DNA (kDNA) for diagnosing visceral leishmaniasis-associated hemophagocytic lymphohistiocytosis (VL-HLH). Three pediatric patients diagnosed with VL-HLH via the microscopic examination of bone marrow smears were selected to explore the diagnostic value of kDNA PCR in Leishmania species identification and parasite load quantification in three cases of visceral leishmaniasis. Total DNA was extracted from the bone marrow samples, and PCR testing targeting the Leishmania kDNA was conducted.

Characterisation of the Novel HLA-C*03:714 Allele by Next-Generation Sequencing.

HLA-C*03:714 differs from HLA-C*03:04:01:01 by one nucleotide substitution at position 685G>A in exon 4.

The Biological Characteristics and Mouse Model of Lassa Virus From the First Imported Case in China.

Lassa fever (LF) is a fatal hemorrhagic disease caused by the Lassa virus (LASV), which mainly spreads in Africa. As China's interactions with Africa become more frequent, the risk of LF being imported into China also rises, making the study of LASV increasingly urgent. In this study, the Lineage IV LASV strain was successfully isolated from the first imported case in China.

Establishment of Coala: a novel 3D and 2D cancer cell line derived from colorectal cancer liver metastasis.

Metastatic colorectal cancer is one of the most critical causes of cancer-related dead in patients suffering this type of malignancy. As the liver metastases are found in almost 25-50% of all colorectal cancer patients, there is an urgent need for suitable in vitro and in vivo models. To the best of our knowledge, only a limited number of well-described 2D or 3D organoid/spheroid cell lines originated from human liver metastases was reported for this type of malignancy and submitted to ATCC and other repository centers for general use.

Immunofocusing design of a fusion glycoprotein monomer vaccine for respiratory syncytial virus.

Respiratory syncytial virus (RSV) can cause severe lower respiratory tract infections in infants and the elderly. Previously, most RSV vaccine antigen design strategies have focused on the stability of the prefusion (PreF) protein trimer conformation. We hypothesized that the RSV monomer might serve as a vaccine candidate immunogen.

Single-cell analysis unravels the role of NK cells and monocytes in the control of SARS-CoV-2 breakthrough infections in vaccinated individuals.

Analyzing the antiviral response of natural killer (NK) cells and monocytes is essential to understanding vaccine protection in an immunized population facing SARS-CoV-2 variant breakthrough infections (BTIs). In this study, in peripheral blood mononuclear cells (PBMCs) from vaccinated individuals with SARS-CoV-2 infections, we observed an increase in adaptive CD57NKG2C NK cells and classical monocytes (CMs). Single-cell sequencing analysis showed that the transcriptomic profiles of IFN-induced IFIT3 and other IFN-stimulated genes exhibited marked upregulation in NK cells, defined as CD56CD57NKG2CIFIT3 NK cells.

Ambident reactivity of enolizable 5-mercapto-1-tetrazoles in trapping reactions with in situ-generated thiocarbonyl -methanides derived from sterically crowded cycloaliphatic thioketones.

The in situ-generated thiocarbonyl -methanides (thiocarbonyl ylides), derived from cycloaliphatic thioketones, are efficiently trapped by enolizable 1-substitued 5-mercapto-1-tetrazoles and formation of the corresponding N-H or S-H insertion products, i.e., thioaminals or dithioacetals, respectively, was observed.

In Vitro Investigation of Statin Effects on Genes Associated with Severe COVID-19 in Cancerous and Non-Cancerous Cells.

The progressive course of coronavirus disease 2019 (COVID-19) is more frequently observed in individuals with obesity, diabetes, pulmonary and cardiovascular disease, or arterial hypertension. Many patients with these conditions are prescribed statins to treat hypercholesterolaemia. However, statins exhibit additional pleiotropic effects.

Platelet-derived microparticles increase the interaction of colorectal cancer cells with the endothelium to promote metastatic events.

Background: The major challenge in colorectal cancer (CRC) therapy involves the formation of distant metastases, which represent the primary cause of treatment failure and patient death. To undergo metastasis, cancer cells of an invasive phenotype must intravasate and extravasate the blood or lymphatic vessels to reach distant sites. Platelet-derived microparticles (PMP) are considered important factors in various diseases, including CRC.

A >7-Year Feeding Study on the Long-Term Effects of Genetically Modified Maize Containing and Genes on Immune Status and Serum Metabolites in Two Generations of Cynomolgus Macaques.

A >7-year study was conducted using cynomolgus macaques () to evaluate the long-term effects of genetically modified (GM) maize on the immune status and serum metabolic profile across two generations. The GM insect-resistant and herbicide-tolerant maize line used carried the and genes. The macaques were maintained on GM maize-based, non-GM maize-based, or normal diet for >7 years, and their offspring received the corresponding diet postweaning.