Aβ as biomarker in Alzheimer’s disease (AD) drives the significant research efforts for developing different biosensors with different sensing strategies, materials, and mechanisms for Aβ detection.

T cell immunoglobulin and mucin domain-3 (TIM-3) is an immune checkpoint that regulates normal immune responses but can be exploited by tumor cells to evade immune surveillance. TIM-3 is primarily expressed on immune cells, particularly on dysfunctional and exhausted T cells, and engagement of TIM-3 with its ligands promotes TIM-3-mediated T cell inhibition. Antagonistic ligand-blocking anti-TIM-3 antibodies have the potential to abrogate T cell inhibition, activate antigen-specific T cells, and enhance anti-tumor immunity. Here we describe M6903, a fully human anti-TIM-3 antibody without effector function and with high affinity and selectivity to TIM-3. We demonstrate that M6903 blocks the binding of TIM-3 to three of its ligands, phosphatidylserine (PtdSer), carcinoembryonic antigen cell adhesionrelated molecule 1 (CEACAM1), and galectin 9 (Gal-9). These results are supported by an atomic resolution crystal structure and functional assays, which demonstrate that M6903 monotherapy enhanced T cell activation. This activation was further enhanced by the combination of M6903 with bintrafusp alfa, a bifunctional fusion protein that simultaneously blocks the transforming growth factorβ (TGF-β) and programmed death ligand 1 (PD-L1) pathways. M6903 and bintrafusp alfa combination therapy also enhanced anti-tumor efficacy in huTIM-3 knock-in mice, relative to either monotherapy. These in vitro and in vivo data, along with favorable pharmacokinetics in marmoset monkeys, suggest that M6903 as a monotherapy warrants further pre-clinical assessment and that M6903 and bintrafusp alfa may be a promising combination therapy in the clinic. ARTICLE HISTORY

The Fanniidae is one of four families in the superfamily Muscoidea (Diptera), including some important medical and hygienic flies. There is a paucity of reports on the ultrastructure of olfactory sensilla for the fanniid species. To provide more information on the morphology of the antennal and palpal sensilla of fanniid fly, Fannia hirticeps (Stein, 1892) has been studied using scanning electron microscopy. The first two antennal segments, scape and pedicel, are covered by microtrichiae and several chaetic sensilla. Six distinct morphological types of sensilla are recorded on the antennal funiculus, including one trichoid, two basiconic, two coeloconic sensilla, and one clavate sensilla. The measurement and density of each sensilla type are also provided. The trichoid sensilla tend to be longer and denser toward the apex of antennal funiculus. Basiconic sensilla spread all over the funicular surface. F. hirticeps bears two types of coeloconic sensilla, type 2 coeloconic sensilla distributed on the distal part of the anterior surface, whereas type 1 distributed on the rest of the funiculus. Clavate sensilla are found on the base of antennal funiculus. Only one large sensory pit is located on the posterior surface. Maxillary palps bear one type of basiconic sensilla. These results are compared with eight other muscid flies. Our findings provide a morphological basis for future investigations on olfactory-mediated behavior of this group.

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Background. There is evidence suggesting that genetic variants in the chondroitin sulfate proteoglycan2 (CSPG2, also known as versican) gene are involved in the pathogenesis of intracranial aneurysms (IAs). Some authors have demonstrated that single nucleotide polymorphisms (SNPs) rs173686 and rs251124 in the promoter region of the CSPG2 gene are associated with IAs. We performed a case-control study to investigate whether these SNPs might affect the development of IAs in Chinese Han nationality.Methods. The study group comprised 240 Chinese Han nationality patients with at least one intracranial aneurysm and 240 healthy Han nationality controls. Genomic DNA was isolated from blood leukocytes. The SNPs rs173686 and rs251124 were genotyped by PCR amplification and DNA sequencing. Differences in genotype and allele frequencies between patients and controls were tested by the chi-square method.Results. Genotype and allele frequencies of the SNPs rs173686 and rs251124 were both demonstrated to be in Hardy-Weinberg equilibrium. No significant difference in genotype or allele frequencies between case and control groups was detected at either of the two SNPs.Conclusions. The data do not support the hypothesis that the two SNPs (rs173686 and rs251124) in the promoter region of the CSPG2 gene influence the development of intracranial aneurysms in Chinese Han nationality.