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.

Versatile photonic molecule switch in multimode microresonators.

Harnessing optical supermode interaction to construct artificial photonic molecules has uncovered a series of fundamental optical phenomena analogous to atomic physics. Previously, the distinct energy levels and interactions in such two-level systems were provided by coupled microresonators. The reconfigurability is limited, as they often require delicate external field stimuli or mechanically altering the geometric factors. These highly specific approaches also limit potential applications. Here, we propose a versatile on-chip photonic molecule in a multimode microring, utilizing a flexible regulation methodology to dynamically control the existence and interaction strength of spatial modes. The transition between single/multi-mode states enables the "switched-off/on" functionality of the photonic molecule, supporting wider generalized applications scenarios. In particular, "switched-on" state shows flexible and multidimensional mode splitting control in aspects of both coupling strength and phase difference, equivalent to the a.c. and d.c. Stark effect. "Switched-off" state allows for perfect low-loss single-mode transition (Qi ~ 10 million) under an ultra-compact bend size (FSR ~ 115 GHz) in a foundry-based silicon microring. It breaks the stereotyped image of the FSR-Q factor trade-off, enabling ultra-wideband and high-resolution millimeter-wave photonic operations. Our demonstration provides a flexible and portable solution for the integrated photonic molecule system, extending its research scope from fundamental physics to real-world applications such as nonlinear optical signal processing and sixth-generation wireless communication.

Ergonomic Design and Performance Evaluation of H-Suit for Human Walking.

A soft exoskeleton for the hip flexion, named H-Suit, is developed to improve the walking endurance of lower limbs, delay muscle fatigue and reduce the activation level of hip flexors. Based on the kinematics and biomechanics of the hip joints, the ergonomic design of the H-Suit system is clearly presented and the prototype was developed. The profile of the auxiliary forces is planned in the auxiliary range where the forces start at the minimum hip angle, reach the maximum (120 N) and end at 90% of each gait cycle. The desired displacements of the traction unit which consist of the natural and elastic displacements of the steel cables are obtained by the experimental method. An assistance strategy is proposed to track the profile of the auxiliary forces by dynamically adjusting the compensation displacement Lc and the hold time Δt. The influences of the variables Lc and Δt on the natural gaits and auxiliary forces have been revealed and analyzed. The real profile of the auxiliary forces can be obtained and is consistent with the theoretical one by the proposed assistance strategy. The H-Suit without the drive unit has little effect on the EMG signal of the lower limbs. In the powered condition, the H-Suit can delay the muscle fatigue of the lower limbs. The average rectified value (ARV) slope decreases and the median frequency (MNF) slope increases significantly. Wearing the H-Suit resulted in a significant reduction of the vastus lateralis effort, averaged over subjects and walking speeds, of 13.3 ± 2.1% (p = 2 × 10-5).

High-gain erbium silicate waveguide amplifier and a low-threshold, high-efficiency laser.

Erbium-doped materials have played an important role in the fabrication of light sources used in silicon photonics. Recent studies demonstrated that erbium silicate nanowire had a high net gain attributable to its high erbium concentration and excellent material quality. We establish a more accurate and comprehensive theoretical model of erbium silicate nanowire, analyze the modeled nanowire's properties, and optimize a high-gain erbium silicate waveguide amplifier and low-threshold, high-efficiency laser by considering upconversion, energy transfer, and amplified spontaneous emission. The simulation results and previous experimental data reported in reference showed some agreement. A proposed waveguide amplifier, based on the optimized design, displayed a gain greater than 20 dB/mm. Then, a 3.3 mW low-threshold laser with a maximum power-conversion efficiency of 50% was modeled by choosing the optimized resonator cavity and reflector. The results indicate that erbium silicate compound materials with large optical gains can serve as potential candidates for inclusion in scale-integrated amplifiers and other applications requiring lasers.

Preparation of doxycycline-imprinted magnetic microspheres by inverse-emulsion suspension polymerization for magnetic dispersion extraction of tetracyclines from milk samples.

A magnetic dispersion extraction method was developed based on a molecularly imprinted magnetic microsphere (MIMM) for the selective clean-up and enrichment of tetracycline antibiotics from milk samples. The MIMMs were prepared by inverse-emulsion suspension polymerization, using doxycycline, trimethylolpropane trimethacrylate, acrylamide, methacrylic acid, and surface-modified Fe3 O4 as a template molecule, crosslinker, functional monomer, and magnetic component, respectively. Synthesis and extraction conditions were optimized for obtaining excellent affinity and high selectivity. The magnetism, covering amount, and selectivity of the magnetic microspheres were characterized by a vibrating sample magnetometer, thermogravimetric analysis, and a competitive recognition experiment. The MIMMs were applied to separate tetracycline antibiotics from milk samples by magnetic dispersion extraction, and an enrichment factor of 9.28 and a good sample clean-up were obtained. The average recoveries of four tetracycline antibiotics were obtained in the range of 74.5-93.8% with a precision of 1.2-5.2%. The LODs and LOQs of the proposed method were in the range of 7.4-19.4 and 24.7-64.7 µg/kg, respectively. The results indicated that magnetic dispersion extraction using MIMMs is a powerful tool for food-sample pretreatment with high selectivity and a simplified procedure.

The complex influence of the oscillatory shear on the melt of linear diblock copolymers.

The phase morphologies of symmetric linear diblock copolymers subjected to the oscillatory shear are investigated with the aid of dissipative particle dynamics simulations. The frequency dependent reorientations of the lamellar phase (LAM) have been identified. We find that the parallel orientation of LAM (i.e., the lamellar normal is parallel to the velocity gradient) appears at high shear frequency, whereas the perpendicular orientation of LAM (the lamellar normal being perpendicular to the velocity gradient) takes place at low shear frequency. In both of the cases, the reorientations undergo similar processes: the original LAM phase prepared in equilibrium breaks down rapidly, and it takes a very long time for the perfectly oriented LAM being reformed. Moreover, the shear-induced isotropic to lamellar phase transitions are observed when the oscillatory shear amplitude is large enough. It indicates that the shear amplitude plays a dominant role in the order-disorder transition. The viscosity and the modulus of the melt are found to be dependent on the shear amplitude and the shear frequency in a complex way.