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Abstract The recent surge in the plant-based protein market has resulted in high demands for soybean genotypes with improved grain yield, seed protein and oil content, and essential amino acids (EAAs). Given the quantitative nature of these traits, complex interactions among seed components, as well as between seed components and environmental factors and management practices, add complexity to the development of desired genotypes. In this study, the across-environment seed protein stability of 449 genetically diverse plant introductions was assessed, revealing that genotypes may display varying sensitivities to such environmental stimuli. The EAAs valine, phenylalanine, and threonine showed the highest variable importance toward the variation in stability, while both seed protein and oil contents were among the explanatory variables with the lowest importance. In addition, 56 single nucleotide polymorphism (SNP) markers were significantly associated with various seed components. Despite the strong phenotypic Pearson’s correlation observed among most seed components, many independent genomic regions associated with one or few seed components were identified. These findings provide insights for improving the seed concentration of specific EAAs and reducing the negative correlation between seed protein and oil contents.

Human adenoviruses (HAdVs) are major respiratory pathogens. Specifically, human adenovirus type 4 (HAdV4) and human adenovirus type 7 (HAdV7) are known for causing fever and pneumonia, with documented cases of fatalities among the population. In recent years, HAdV4/HAdV7 has been implicated in causing substantial outbreaks, leading to increased morbidity in multiple countries. Most HAdV4 and HAdV7 infections have been reported in North America, Asia, Europe, Africa, South America, Oceania, and the Middle East. Most fatalities occurred in North America (the United States) and Asia (China and Singapore). Engineered recombinant adenoviruses have played a crucial role as vaccine vectors. In this study, we constructed a recombinant adenovirus, Ad4ITRmut-Ad7E3, and evaluated it in vitro and in vivo. We observed that the replication rate of Ad4ITRmut-Ad7E3 was lower than that of the RI-67 strain, indicating that the mutation of inverted terminal repeats (ITRs) weakened the replication ability of HAdV4. Immunization of BALB/c mice with the bivalent Ad4ITRmut-Ad7E3 vaccine strain, administered by intraperitoneal injection and oral gavage, resulted in the elicitation of neutralizing antibodies targeting HAdV4 and HAdV7. This finding not only provides a novel method and technique for the efficient construction of a polyvalent recombinant adenovirus vaccine candidate against HAdV4 and HAdV7 but also against other prevalent adenovirus serotypes such as HAdV3, HAdV11, HAdV14, and HAdV55, from various regions.

The human JC polyomavirus (JCV) is a widespread, neurotropic, opportunistic pathogen responsible for progressive multifocal leukoencephalopathy (PML) as well as other diseases in immunosuppressed individuals, including granule cell neuronopathy, JCV-associated nephropathy, encephalitis, and meningitis in rare cases. JCV classification is still unclear, where the ICTV (International Committee on Taxonomy of Viruses) has grouped all the strains into human polyomavirus 2, with no classification on clade and subclade levels. Therefore, JCV strains were previously classified using different genomic regions, e.g., full-length, VP1, and the V-T intergenic region etc., and the strains were grouped into several types related to various geographic locations and human ethnicities. However, neither of these classifications and nomenclature contemplates all the groups described so far. Herein, we evaluated all the available full-length coding genomes, VP1, and large T antigen nucleotide sequences of JCV reported during 1993–2023 and classified them into four major phylogenetic clades, i.e., GI-GIV, where GI is further grouped into two types GI.1 and GI.2 with five sub-clades each (GI.1/GI.2 a-e), GII into three (GII a-c), GIII as a separate clade, and GIV into seven sub-clades (GIV a-g). Similarly, the phylogeographic network analysis indicated four major clusters corresponding to GI-GIV clades, each with multiple subclusters and mutational sub-branches corresponding to the subclades. GI and GIV clusters are connected via GI.1-e reported from Europe and America, GII, GIII and GIV clusters are connected by GII-b and GII-c strains reported from Africa, while GIV cluster strains are connected to the Russia-Italy JCV haplotype. Furthermore, we identified JCV-variant-GS/B-Germany-1997 (GenBank ID: AF004350.1) as an inter-genotype recombinant having major and minor parents in the GI.1-e and GII-a clades, respectively. Additionally, the amino acid variability analysis revealed high entropy across all proteins. The large T antigen exhibited the highest variability, while the small t antigen showed the lowest variability. Our phylogenetic and phylogeographic analyses provide a new approach to genotyping and sub-genotyping and present a comprehensive classification system of JCV strains based on their genetic characteristics and geographic distribution, while the genetic recombination and amino acid variability can help identify pathogenicity and develop effective preventive and control measures against JCV infections.

Summary: Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant disease with a poor prognosis due to inefficient diagnosis and tenacious drug resistance. Obg-like ATPase 1 (OLA1) is overexpressed in many malignant tumors. The molecular mechanism of OLA1 underlying gemcitabine (GEM)-induced drug resistance was investigated in this study. An enhanced expression of OLA1 was observed in a GEM acquired resistant pancreatic cancer cell lines and in patients with pancreatic cancer. Overexpressed OLA1 showed poor overall survival rates in patients with pancreatic cancer. Dysregulation of the OLA1 reduced expression of CD44+/CD133+, and improved the sensitivity of pancreatic cancer cells to GEM. OLA1 highly expression facilitated the formation of the OLA1/Sonic Hedgehog (SHH)/Hedgehog-interacting protein (HHIP) complex in nuclei, resulting in the inhibition of negative feedback of Hedgehog signaling induced by HHIP. This study suggests that OLA1 may be developed as an innovative drug target for an effective therapy of pancreatic cancer.

To break the high additional mass ratio requirement of traditional vibration absorbing materials/devices, and overcome the shortcoming of the narrow operating frequency band of conventional local resonance metamaterial dampers, this paper proposes a lightweight multi-scale material/structure integrated elastic metamaterial for broadband vibration absorption. By replacing the mass components in the macroscopic metamaterial vibration absorber with a composite mass body filled with microscopic particle materials, a multi-scale structure/material integrated design between the macroscopic oscillator and microscopic particle is realized. The macroscopic oscillator absorbs low-frequency vibration, while the microscopic particle cluster absorbs medium–high frequency vibration, thereby achieving a broadband vibration absorption covering the low-medium–high ranges. Based on the band gap theory and the multiphase flow theory of gas-particle, this paper systematically analyzes the band gap effect of multi-scale metamaterials and the dissipation capacity of medium–high frequency caused by particle damping. The structure exhibits commendable vibration damping performance. The multi-scale integrated vibration damper retains the lightweight and sub-wavelength characteristics of the traditional local resonance unit cells, while greatly broadening the working bandwidth, and having potential applications in low-frequency broadband vibration reduction of various mechanical equipment.