Media 1: Stabilized high-accuracy correction of ocular aberrations with liquid crystal on silicon spatial light modulator in adaptive optics retinal imaging system

Originally published in Optics Express on 01 August 2011 (oe-19-16-15026

Table1_Effectiveness and safety of pelareorep plus chemotherapy versus chemotherapy alone for advanced solid tumors: a meta-analysis.docx

Background: Pelareorep is an oncolytic virus that causes oncolytic effects in many solid tumors, and it has shown therapeutic benefits. However, few studies have compared pelareorep combined with chemotherapy to traditional chemotherapy alone in advanced solid tumors. Consequently, we intended to evaluate the effectiveness and safety of pelareorep plus chemotherapy in this paper.Methods: We searched four databases including PubMed, Embase, Cochrane Library and Web of Science comprehensively for studies comparing pelareorep combined with chemotherapy to chemotherapy alone in the treatment of advanced solid tumors. The outcomes measures were 1-year overall survival (OS), 2-year OS, 4-month progression-free survival (PFS), 1-year PFS, objective response rate (ORR), any-grade adverse events (any-grade AEs), and severe AEs (grade ≥ 3).Results: There were five studies involving 492 patients included in the study. Combination therapy did not significantly improve clinical outcomes in terms of 1-year OS [RR = 1.02, 95%CI = (0.82–1.25)], 2-year OS [RR = 1.00, 95%CI = (0.67–1.49)], 4-month PFS [RR = 1.00, 95%CI = (0.67–1.49)], 1-year PFS [RR = 0.79, 95%CI = (0.44–1.42)], and ORR [OR = 0.79, 95%CI = (0.49–1.27)] compared to chemotherapy alone, and the subgroup analysis of 2-year OS, 1-year PFS, and ORR based on countries and tumor sites showed similar results. In all grades, the incidence of AEs was greater with combination therapy, including fever [RR = 3.10, 95%CI = (1.48–6.52)], nausea [RR = 1.19, 95%CI = (1.02–1.38)], diarrhea [RR = 1.87, 95%CI = (1.39–2.52)], chills [RR = 4.14, 95%CI = (2.30–7.43)], headache [RR = 1.46, 95%CI = (1.02–2.09)], vomiting [RR = 1.38, 95%CI = (1.06–1.80)] and flu-like symptoms [RR = 4.18, 95%CI = (2.19–7.98)]. However, severe adverse events did not differ significantly between the two arms.Conclusion: Pelareorep addition to traditional chemotherapy did not lead to significant improvements in OS, PFS, or ORR in advanced solid tumor patients, but it did partially increase AEs in all grades, with no discernible differences in serious AEs. Therefore, the combination treatment is not recommended in patients with advanced solid tumors.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=400841, identifier CRD42023400841</p

An Updated Meta-Analysis of Fatal Adverse Events Caused by Bevacizumab Therapy in Cancer Patients

<div><p>Background</p><p>The risk of fatal adverse events (FAEs) due to bevacizumab-based chemotherapy has not been well described; we carried out an updated meta-analysis regarding this issue.</p><p>Methods</p><p>An electronic search of Medline, Embase and The Cochrane Central Register of Controlled Trials was conducted to investigate the effects of randomized controlled trials on bevacizumab treatment on cancer patients. Random or fixed-effect meta-analytical models were used to evaluate the risk ratio (RR) of FAEs due to the use of bevacizumab.</p><p>Results</p><p>Thirty-four trials were included. Allocation to bevacizumab therapy significantly increased the risk of FAEs; the RR was 1.29 (95% CI:1.05–1.57). This association varied significantly with tumor types (<i>P</i> = 0.002) and chemotherapeutic agents (<i>P</i> = 0.005) but not with bevacizumab dose (<i>P</i> = 0.90). Increased risk was seen in patients with non–small cell lung cancer, pancreatic cancer, prostate cancer, and ovarian cancer. However, FAEs were lower in breast cancer patients treated with bevacizumab. In addition, bevacizumab was associated with an increased risk of FAEs in patients who received concomitant agents of taxanes and/or platinum.</p><p>Conclusion</p><p>Compared with chemotherapy alone, the addition of bevacizumab was associated with an increased risk of FAEs among patients with special tumor types, particularly when combined with chemotherapeutic agents such as platinum.</p></div

Risk ratio of fatal adverse events by subgroup.

<p>NSCLC, non– small cell lung cancer; SCLC, small cell lung cancer; RR, risk ratio; PFS, progression-free survival; NA, not applicable.</p

Fatal adverse events by specific type.

<p>Fatal adverse events by specific type.</p

Greatly Enhanced Plasmon–Exciton Coupling in Si/WS₂/Au Nanocavities

A strong light–matter interaction is highly desirable from the viewpoint of both fundamental research and practical application. Here, we propose a dielectric–metal hybrid nanocavity composed of a silicon (Si) nanoparticle and a thin gold (Au) film and investigate numerically and experimentally the coupling between the plasmons supported by the nanocavity and the excitons in an embedded tungsten disulfide (WS2) monolayer. When a Si/WS2/Au nanocavity is excited by the surface plasmon polariton generated on the surface of the Au film, greatly enhanced plasmon–exciton coupling originating from the hybridization of the surface plasmon polariton, the mirror-image-induced magnetic dipole, and the exciton modes is clearly revealed in the angle- or size-resolved scattering spectra. A Rabi splitting as large as ∼240 meV is extracted by fitting the experimental data with a coupled harmonic oscillator model containing three oscillators. Our findings open new horizons for constructing nanoscale photonic devices by exploiting dielectric–metal hybrid nanocavities

Study flow diagram.

<p>Study flow diagram.</p

Characteristics of studies included in primary analysis.

<p>*Number of patients for safety analysis; NSCLC, non– small cell lung cancer; SCLC, small cell lung cancer.</p

Risk ratio of fatal adverse events in cancer participants treatment with bevacizumab compare with control.

<p>Risk ratio of fatal adverse events in cancer participants treatment with bevacizumab compare with control.</p

Engineered extracellular vesicles for delivering functional Cas9/gRNA to eliminate hepatitis B virus cccDNA and integration

The persistence of HBV covalently closed circular DNA (cccDNA) and HBV integration into the host genome in infected hepatocytes pose significant challenges to the cure of chronic HBV infection. Although CRISPR/Cas9-mediated genome editing shows promise for targeted clearance of viral genomes, a safe and efficient delivery method is currently lacking. Here, we developed a novel approach by combining light-induced heterodimerization and protein acylation to enhance the loading efficiency of Cas9 protein into extracellular vesicles (EVs). Moreover, vesicular stomatitis virus-glycoprotein (VSV-G) was incorporated onto the EVs membrane, significantly facilitating the endosomal escape of Cas9 protein and increasing its gene editing activity in recipient cells. Our results demonstrated that engineered EVs containing Cas9/gRNA and VSV-G can effectively reduce viral antigens and cccDNA levels in the HBV-replicating and infected cell models. Notably, we also confirmed the antiviral activity and high safety of the engineered EVs in the HBV-replicating mouse model generated by hydrodynamic injection and the HBV transgenic mouse model. In conclusion, engineered EVs could successfully mediate functional CRISPR/Cas9 delivery both in vitro and in vivo, leading to the clearance of episomal cccDNA and integrated viral DNA fragments, and providing a novel therapeutic approach for curing chronic HBV infection.</p