The Oncolytic virus VT1092M and an Anti-PD-L1 antibody synergize to induce systemic antitumor immunity in a murine bilateral tumor model.

This study investigated the synergistic potential of an oncolytic herpes simplex virus armed with interleukin 12 (VT1092M) in combination with immune checkpoint inhibitors for enhancing antitumor responses. The potential of this combination treatment to induce systemic antitumor immunity was assessed using bilateral subcutaneous tumor and tumor re-challenge mouse models. The antitumor efficacy of various OV and ICI treatment combinations and the underlying mechanisms were explored through diverse analytical techniques, including flow cytometry and RNA sequencing. Using VT1092M, either alone or in combination with an anti-PD-L1 antibody, significantly reduced the sizes of both the injected and untreated abscopal tumors in a bilateral tumor mouse model. The combination therapy demonstrated superior antitumor efficacy to the other treatment conditions tested, which was accompanied by an increase in T cell numbers and CD8+T cell activation. Results from the survival and tumor re-challenge experiments showed that the combination therapy elicited long-term, tumor-specific immune responses, which were associated with tumor clearance and prolonged survival. Immune cell depletion assays identified CD8+T cells as the crucial mediators of systemic antitumor immunity during combination therapy. In conclusion, the combination of VT1092M and PD-L1 blockade emerged as a potent inducer of antitumor immune responses, surpassing the efficacy of each monotherapy. This synergistic approach holds promise for achieving robust and sustained antitumor immunity, with potential implications for preventing tumor metastasis in patients with cancer.

Genome-Wide Identification of the Highly Conserved INDETERMINATE DOMAIN (IDD) Zinc Finger Gene Family in Moso Bamboo (Phyllostachys edulis).

INDETERMINATE DOMAIN (IDD) proteins, a family of transcription factors unique to plants, function in multiple developmental processes. Although the IDD gene family has been identified in many plants, little is known about it in moso bamboo. In this present study, we identified 32 PheIDD family genes in moso bamboo and randomly sequenced the full-length open reading frames (ORFs) of ten PheIDDs. All PheIDDs shared a highly conserved IDD domain that contained two canonical C2H2-ZFs, two C2HC-ZFs, and a nuclear localization signal. Collinearity analysis showed that segmental duplication events played an important role in expansion of the PheIDD gene family. Synteny analysis indicated that 30 PheIDD genes were orthologous to those of rice (Oryza sativa). Thirty PheIDDs were expressed at low levels, and most PheIDDs exhibited characteristic organ-specific expression patterns. Despite their diverse expression patterns in response to exogenous plant hormones, 8 and 22 PheIDDs responded rapidly to IAA and 6-BA treatments, respectively. The expression levels of 23 PheIDDs were closely related to the outgrowth of aboveground branches and 20 PheIDDs were closely related to the awakening of underground dormant buds. In addition, we found that the PheIDD21 gene generated two products by alternative splicing. Both isoforms interacted with PheDELLA and PheSCL3. Furthermore, both isoforms could bind to the cis-elements of three genes (PH02Gene17121, PH02Gene35441, PH02Gene11386). Taken together, our work provides valuable information for studying the molecular breeding mechanism of lateral organ development in moso bamboo.

Adsorption-Reaction Processes Between Gelatin and PDMS-E Emulsion Droplets.

In this work, the effects of droplet size and reaction time on the adsorption-reaction processes between gelatin and α-[3-(2,3-epoxypropoxy) propyl]-ω-butyl-polydimethylsiloxane (PDMS-E) emulsion droplets were studied. Gelatin molecules were only physically adsorbed on the surface of the PDMS-E droplet in the 0-75 min range, which was unrelated to the droplet size (100-1000 nm). For the small-size droplets (<410 nm), the physical adsorption proceeded over 75 min followed by agglomeration. For middle-size droplets (410-680 nm), the physical adsorption finished at 125 min; subsequently, the nucleophilic reaction between the primary amino group and the epoxy group began to happen, and globular-like or core-shell colloidal particles were formed. For large-size droplets (>680 nm), the nucleophilic reaction occurred at 75 min and produced core-shell or multi-layered colloidal particles. In a word, the physical absorption or nucleophilic reaction between gelatin and PDMS-E emulsion droplets could be controlled by controlling the droplet size and reaction time. Furthermore, the soft tissue paper coated with large-size droplets exhibited excellent resistance to water permeability and flame-resistant performance, which were carried out by water resistance and flammability tests.

C1q/TNF-related protein 9 improves the anti-contractile effects of perivascular adipose tissue via the AMPK-eNOS pathway in diet-induced obese mice.

The anti-contractile property of perivascular adipose tissue (PVAT) is abolished through an endothelium-dependent pathway in obesity. C1q/tumor necrosis factor-related protein (CTRP)9 improved endothelial function by promoting endothelium-dependent vasodilatation. The aims of this study were to investigate whether CTRP9 improves the anti-contractile effect of PVAT and protects against PVAT dysfunction in obese mice. The mice were treated with a high-fat diet with or without CTRP9 treatment. Thoracic aortas with or without PVAT (PVAT+ or PVAT-) were prepared, and concentration-dependent responses to phenylephrine were measured. Obese mice showed a significantly increased contractile response, which was suppressed by CTRP9 treatment both with and without PVAT. PVAT significantly reduced the anti-contractile effect in obese mice, which was partially restored by CTRP9 treatment. Treatment of the aortic rings (PVAT+) with inhibitors of AMP protein kinase (AMPK), Akt and endothelial nitric oxide synthase (eNOS) attenuated the beneficial effect of CTRP9 on PVAT. Similar results were observed when we pretreated the aortic rings with CTRP9 ex vivo. CTRP9 significantly enhanced the phosphorylation levels of AMPK, Akt and eNOS, and reduced superoxide production and TNF-α levels in PVAT from obese mice. Our study suggests that CTRP9 enhanced the anti-contractile effect of PVAT and improved PVAT function by activating the AMPK-eNOS pathway in obese mice.