Preliminary efficacy and safety of YSCH-01 in patients with advanced solid tumors: an investigator-initiated trial.

OBJECTIVE: To evaluate the safety and preliminary efficacy of YSCH-01 (Recombinant L-IFN adenovirus) in subjects with advanced solid tumors. METHODS: In this single-center, open-label, investigator-initiated trial of YSCH-01, 14 patients with advanced solid tumors were enrolled. The study consisted of two distinct phases: (1) the dose escalation phase and (2) the dose expansion phase; with three dose groups in the dose escalation phase based on dose levels (5.0×109 viral particles (VP)/subject, 5.0×1010 VP/subject, and 5.0×1011 VP/subject). Subjects were administered YSCH-01 injection via intratumoral injections. The safety was assessed using National Cancer Institute Common Terminology Criteria for Adverse Events V.5.0, and the efficacy evaluation was performed using Response Evaluation Criteria in Solid Tumor V.1.1. RESULTS: 14 subjects were enrolled in the study, including 9 subjects in the dose escalation phase and 5 subjects in the dose expansion phase. Of the 13 subjects included in the full analysis set, 4 (30.8%) were men and 9 (69.2%) were women. The most common tumor type was lung cancer (38.5%, 5 subjects), followed by breast cancer (23.1%, 3 subjects) and melanoma (23.1%, 3 subjects). During the dose escalation phase, no subject experienced dose-limiting toxicities. The content of recombinant L-IFN adenovirus genome and recombinant L-IFN protein in blood showed no trend of significant intergroup changes. No significant change was observed in interleukin-6 and interferon-gamma. For 11 subjects evaluated for efficacy, the overall response rate with its 95% CI was 27.3% (6.02% to 60.97%) and the disease control rate with its 95% CI was 81.8% (48.22% to 97.72%). The median progression-free survival was 4.97 months, and the median overall survival was 8.62 months. In addition, a tendency of decrease in the sum of the diameters of target lesions was observed. For 13 subjects evaluated for safety, the overall incidence of adverse events (AEs) was 92.3%, the overall incidence of adverse drug reactions (ADRs) was 84.6%, and the overall incidence of >Grade 3 AEs was 7.7%, while no AEs/ADRs leading to death occurred. The most common AEs were fever (69.2%), nausea (30.8%), vomiting (30.8%), and hypophagia (23.1%). CONCLUSIONS: The study shows that YSCH-01 injections were safe and well tolerated and exhibited preliminary efficacy in patients with advanced solid tumors, supporting further investigation to evaluate its efficacy and safety. TRIAL REGISTRATION NUMBER: NCT05180851.

HIF-1α regulates DcR3 to promote the development of endometriosis.

OBJECTIVE: The aim of this study was to investigate the expression and clinical significance of HIF-1α and DcR3 in endometriosis by analysing clinical case data. Tissue samples were collected for tissue chip analysis and staining, and human endometrial stromal cells were isolated and cultured for cell experiments. Additionally, experiments were conducted on collected peritoneal fluid to explore the association and role of HIF-1α and DcR3 in endometriosis. STUDY DESIGN: Patients who visited the Department of Obstetrics and Gynaecology at Central Hospital in Fengxian District, Shanghai, from January 2018 to December 2021 were recruited for this controlled study. Clinical data and tissue chip staining results were collected for multiple regression analysis on the clinical significance of HIF-1α and DcR3. Endometrial tissue, ovarian cysts, and pelvic fluid were collected, and human endometrial stromal cells were cultured. The impact of HIF-1α on DcR3 in different oxygen environments and its role in endometriosis were investigated through PCR, Western blotting, enzyme-linked immunosorbent assay, as well as adhesion and migration assays. RESULTS: In patients with endometriosis, the expression of DcR3 and HIF-1α was found to be upregulated and correlated in ectopic endometrium. The expression of DcR3 served as an indicator of the severity of endometriosis. Hypoxia induced the expression of DcR3, which was regulated by HIF-1α and promoted migration and adhesion. CONCLUSION: DcR3 can be used as a clinical indicator to assess the severity of endometriosis. The hypoxic environment in endometriosis enhances disease progression by regulating DcR3 through HIF-1α.

Transmission of sub-terahertz signals over a fiber-FSO-5†G NR hybrid system with an aggregate net bit rate of 227.912 Gb/s.

Transmission of sub-terahertz (sub-THz) signals over a fiber-free-space optical (FSO)-fifth-generation (5 G) new radio (NR) hybrid system is successfully realized. It is a promising system that utilizes multiple media of optical fiber, optical wireless, and 5 G NR wireless to achieve a 227.912-Gb/s record-high aggregate net bit rate. The system concurrently transmits a 59.813-Gb/s net bit rate in the 150-GHz sub-THz frequency, 74.766-Gb/s in the 250-GHz sub-THz frequency, and 93.333-Gb/s in the 325-GHz sub-THz frequency through the fiber-FSO-wireless convergence, including 25-km single-mode fiber, 100-m FSO, and 30-m/25-m/20-m sub-THz-wave transmissions. This system achieves sufficiently low bit error rates (< hard-decision forward error correction (FEC) threshold of 3.8 × 10-3 at 16 and 20 Gbaud symbol rates; < soft-decision FEC threshold of 2 × 10-2 at 28 Gbaud symbol rate) and clear and distinct constellation diagrams, meeting the demands of 5 G NR communications in the sub-THz band. The development of fiber-FSO-5 G NR hybrid system represents a substantial development in the field of advanced communications. It has the ability to enhance the way we communicate in the future.

A 400-Gb/s WDM-PAM4 OWC system through the free-space transmission with a water-air-water link.

A 400-Gb/s wavelength-division-multiplexing (WDM) four-level pulse amplitude modulation (PAM4) optical wireless communication (OWC) system through a 200-m free-space transmission with either an 8.8-m piped water-air-piped water link or a 6.5-m turbid water-air-turbid water link is successfully constructed. Incorporating PAM4 modulation with an 8-wavelength WDM scheme greatly increases the total transmission rate of the WDM-PAM4 OWC system to 400 Gb/s (50 Gb/s/λ × 8 λs). By adopting doublet lenses in free-space transmission, a laser beam reducer/expander and a reflective spatial light modulator (SLM) with an angle expander through the water-air-water link, good bit error rate performance and acceptable PAM4 eye diagrams are obtained. Using a reflective SLM with an angle expander not only adaptively adjusts the laser beam, but also effectively solves the oceanic engineering problems. This demonstrates WDM-PAM4 OWC system outperforms existing OWC systems through the free-space transmission with an air-water-air link because it can solve the practical engineering problems in actual oceanic environments.

800 Gb/s/200 m FSO link with a WDM-PAM4 scheme and SLM-based beam tracking technology.

An 800 Gb/s/200 m free-space optical (FSO) link with a wavelength-division multiplexing (WDM)-four-level pulse amplitude modulation (PAM4) scheme and spatial light modulator (SLM)-based beam tracking technology is constructed. To the best of our knowledge, this is the first one that adopts a WDM-PAM4 scheme and an SLM-based beam tracking technology to simultaneously afford a high transmission capacity of 800 Gb/s and resolve the laser beam misalignment problem due to target device movement. By adopting a 16-wavelength WDM-PAM4 scheme, the transmission capacity of the FSO link is considerably enhanced with an 800 Gb/s (50Gb/sPAM4/λ×16λ) total capacity. By deploying an SLM-based beam tracking technology, the laser beam misalignment problem is practically resolved for providing an FSO link with high link accessibility. This demonstrated WDM-PAM4 FSO link fully meets the requirements of high-speed, long-reach, and high-reliability transmissions.

Dysregulation of miRNA-21 and their potential as biomarkers for the diagnosis of cervical cancer.

OBJECTIVE: This study aimed to characterize the miR-21 and evaluated its clinical significance. METHODS: Total RNA was extracted from 30 pairs of fresh specimens of cervical cancer and normal tissues. The expression levels of the miR-21-3p and miR-21-5p were detected by quantitative reverse transcriptase polymerase chain reaction, with U6 as the internal reference gene. We compared the expression of miR-21-3p and miR-21-5p between study group and control groups, the association between miRNA expression level and clinicopathological factors was investigated. RESULTS: The expression of miR-21-3p and miR-21-5p in HPV positive cervical cancer samples was significantly upregulated compared to that in the paired normal samples (P < 0.05); A multivariate analysis demonstrated that the expression of miR-21 was associated with clinicopathological parameters, including depth of invasion and lymph node metastasis. CONCLUSIONS: MiR-21 upregulation is associated with aggressive progression and poor prognosis in cervical cancer, which suggests that miR-21 might be identified as an independent marker for predicting the clinical outcome of cervical cancer patients.