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Biology subjects

Vella, A.

Publications and source records attributed to Vella, A..

3 recordsLinked to original sources

Radiotherapy Enhancement by Gold Nanocluster-functionalized Nanoliposomes Using Polychromatic Orthovoltage X-ray Irradiation

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers, as the most effective chemoradiation therapies achieve unsatisfactory outcomes while associated with high toxicity. Nanoliposomal drug delivery systems are widely used to improve chemotherapy safety, yet passive release of amphiphilic drugs may still associate with adverse toxicity. To address this, we previously developed nanoliposomes functionalized with hydrophobic gold nanoclusters, demonstrating radiocatalytic activity and enhanced chemoradiotherapy effects in 3D PDAC microtumors under synchrotron irradiation. In this study, gold nanocluster-functionalized nanoliposomes (AuLPs) were optimized and evaluated under 220 kVp orthovoltage X-ray irradiation, widely used in preclinical irradiation systems. AuLPs containing 0.2 mol% gold nanoclusters produced 1.5-fold more reactive oxygen species than unloaded liposomes. However, higher molar ratios were necessary to improve radiotherapy outcomes in 3D PDAC microtumor models following 4 and 8 Gy irradiation. Pharmacokinetics and biodistribution evaluations showed a modest increase in tumor gold content 24 hours post-injection in orthotopic PDAC models. Altogether, these results underscore the potential of gold-radiotherapy-responsive liposomes while highlighting critical formulation challenges, which must be resolved for full therapeutic potential.

bioengineering↗

The genome sequence of the Violet Carpenter Bee, Xylocopa violacea (Linnaeus, 1785): a hymenopteran species undergoing range expansion.

We present a reference genome assembly from an individual male Violet Carpenter Bee (Xylocopa violacea, Linnaeus, 1758). The assembly is 1.02 gigabases in span. 48% of the assembly is scaffolded into 17 pseudo-chromosomal units. The mitochondrial genome has also been assembled and is 21.8 kilobases in length. The genome is highly repetitive, likely representing a highly heterochromatic architecture expected of bees from the genus Xylocopa. We also use an evidence-based methodology to annotate 10,152 high confidence coding genes. This genome was sequenced as part of the pilot project of the European Reference Genome Atlas (ERGA) and represents an important addition to the genomic resources available for Hymenoptera.

genomics↗

Macrophage scavenger receptor 1 controls Chikungunya virus infection through autophagy

Macrophage scavenger receptor 1 (MSR1) mediates the endocytosis of modified low-density lipoproteins and plays an important antiviral role. However, the molecular mechanism underlying MSR1 antiviral actions remains elusive. Herein, we report that MSR1 activates autophagy to restrict infection of Chikungunya virus (CHIKV), an arthritogenic alphavirus that causes acute and chronic crippling arthralgia. Msr1 expression was rapidly upregulated after CHIKV infection in mice. Msr1 knockout mice had elevated viral loads and increased susceptibility to CHIKV arthritis along with a normal type I IFN response. Induction of LC3 lipidation by CHIKV, a marker of autophagy, was reduced in Msr1-/- cells. Mechanistically, MSR1 interacted with ATG12 through its cytoplasmic tail and this interaction was enhanced by CHIKV nsP1 protein. MSR1 repressed CHIKV replication through ATG5-ATG12-ATG16L1 and this was dependent on the FIP200-and-WIPI2-binding domain, but not the WD40 domain of ATG16L1. Our results elucidate an antiviral role for MSR1 involving the autophagic function of ATG5-ATG12-ATG16L1.

microbiology↗