Phase 1b study of first-line fuzuloparib combined with modified FOLFIRINOX followed by fuzuloparib maintenance monotherapy in pancreatic adenocarcinoma.

Background: Chemotherapy remains the standard first-line treatment for pancreatic adenocarcinoma, but with limited efficacy. We aimed to explore the feasibility of adding the PARP inhibitor fuzuloparib to mFOLFIRINOX in the locally advanced/metastatic (LA/M) setting.

Methods: This was the dose-escalation and -expansion, phase 1b portion of a phase 1b/2 study.

Final analysis of camrelizumab plus chemotherapy for untreated advanced or metastatic esophageal squamous cell carcinoma: The ESCORT-1st trial.

Background: The interim analysis of the randomized phase 3 ESCORT-1st study demonstrated significantly longer overall survival (OS) and progression-free survival (PFS) for camrelizumab-chemotherapy than placebo-chemotherapy in untreated advanced/metastatic esophageal squamous cell carcinoma (ESCC). Here, we present the final analysis of this study and investigate potential indicators associated with OS.

Methods: Patients were randomized 1:1 to receive camrelizumab (200 mg) or placebo, both in combination with up to six cycles of paclitaxel (175 mg/m) and cisplatin (75 mg/m).

Ultra-broadband on-chip power splitters for arbitrary ratios on silicon-on-insulator.

We propose and demonstrate on-chip power splitters based on adiabatic rib waveguide enabling arbitrary splitting ratios on a monolithic silicon photonic platform. The devices are elaborately engineered based on adiabatic directional couplers with a trapezoid-structure in the longitudinal direction in the mode evolution region. The measurement results indicate that the proposed devices can achieve over 150 nm bandwidth for arbitrary splitting ratios of 50%:50%, 70%:30% and 90%:10%.

Association between circHIPK3/miR-378a-3p/HDAC4 axis and osteoporotic fractures: A comprehensive investigation.

Background: Osteoporotic fractures (OFs) are a significant public health issue, which can lead to pain and impaired mobility. The underlying mechanisms of OFs remain unclear, but recent studies have suggested that the circRNA-miRNA-mRNA pathway may play a crucial role.

Purpose: This study aimed to investigate the potential involvement of the circHIPK3/miR-378a-3p/HDAC4 pathway in the pathogenesis of OFs.

X-Intersected Silicon Modulator of Well-Rounded Performance.

In silicon modulator design, implantation is always a key factor, significantly influencing the doping profile and carrier distribution. As waveguide doping is limited by the compact footprint of the modulator rib, three-dimensional complex optimization is a viable option to improve performance. This work proposes an X-intersected modulator based on two inversely slanted junctions using the effective 3D Monte Carlo method for junction generation.

CLDN18.2 and 4-1BB bispecific antibody givastomig exerts antitumor activity through CLDN18.2-expressing tumor-directed T-cell activation.

Background: Claudin18.2 (CLDN18.2) is a tight junction protein that has been identified as a clinically proven target in gastric cancer.

Compact, ultrabroadband and temperature-insensitive arbitrary ratio power splitter based on adiabatic rib waveguides.

We propose a compact, ultrabroadband and temperature-insensitive adiabatic directional coupler based on rib silicon waveguide-enabling arbitrary splitting ratios. Simulation results show that the device can achieve arbitrary splitting ratios from 1400 to 1600 nm, equal to 50%:50%, 60%:40%, 70%:30%, 80%:20%, and 90%:10% for the fundamental transverse electric mode. The designed device has an excess loss of less than 0.

Silicon modulator based on omni junctions by effective 3D Monte-Carlo method.

3D doping structure has significant advantages in modulation efficiency and loss compared with 2D modulator doping profiles. However, to the best of our knowledge, previous work on 3D simulation methods for interdigitated doping designs applied simplified models, which prohibited complex 3D doping. In this work, innovative omni junctions, based on the effective 3D Monte-Carlo method, are believed to be the first proposed for high-performance modulators.

Broadband and CMOS compatible polarization splitter-rotator based on a bi-level taper.

A silicon-on-insulator polarization diversity scheme is proposed. Based on an asymmetrical evanescent coupler, a broadband and compact polarization splitter-rotator comprising mode conversion tapers and mode sorting asymmetric Y junctions is optimized with silicon dioxide upper cladding and a silicon nitride waveguide. The simulation results show mode conversion loss is less than 0.

Probing Synergistic Targets by Natural Compounds for Hepatocellular Carcinoma.

Background: Designing combination drugs for malignant cancers has been restricted due to the scarcity of synergy-medicated targets, while some natural compounds have demonstrated potential to enhance anticancer effects.

Methods: We here explored the feasibility of probing synergy-mediated targets by Berberine (BER) and Evodiamine (EVO) in hepatocellular carcinoma (HCC). Using the genomics-derived HCC signaling networks of compound treatment, NF-κB and c-JUN were inferred as key responding elements with transcriptional activity coinhibited during the synergistic cytotoxicity induction in BEL-7402 cells.

Likelihood ratio test for genetic association study with case-control data under Probit model.

Probit and Logit models are the most popular for binary disease statusing in genetic association studies. They are equally used and nearly exchangeable in the analysis of prospectively collected data. However, no strong inferences were made based on Probit models for the retrospectively collected case-control data, especially in the presence of random effects.

Real-world emissions of construction mobile machines and comparison to a non-road emission model.

This study implemented real-world tests in Nanjing, China for measuring emission factors (EFs) of air pollutants, including Carbon Monoxide (CO), Hydrocarbon (HC), Nitrogen Oxides (NO), and Particulate Matter (PM) from ten construction machines in three operational modes (idling, moving, and working) with a Portable Emission Measurement System. The idling mode shows the least variation of EFs, and its average CO EFs can be higher than the moving and working modes by 43% and 34%, respectively. The working mode generates the highest emission for all other pollutants with the highest variation.

Foliar application of Zn reduces Cd accumulation in grains of late rice by regulating the antioxidant system, enhancing Cd chelation onto cell wall of leaves, and inhibiting Cd translocation in rice.

Paddy soil contaminated by cadmium (Cd) has attracted worldwide attention, while foliar spraying of zinc (Zn) could be considered a cost-effective and practical agronomic measure for reducing Cd accumulation in rice grain. However, the effects due to foliar spraying of Zn on different cultivars, as well as the mechanism of subsequent processes taking place are not fully understood up to now. To go a step ahead, a field experiment was conducted with the aim of studying the capability of foliar application of Zn (0.

Compact, broadband, and low-loss silicon photonic arbitrary ratio power splitter using adiabatic taper.

The arbitrary ratio power splitter is widely used in photonic integrated circuits (PICs), for signal monitoring, power equalization, signal feedback, and so on. Here we designed a fabrication-tolerant, compact, broadband, and low-loss arbitrary ratio power splitter. The proposed arbitrary ratio power splitter was realized with an adiabatically tapered silicon rib waveguide with 70 nm shallow etches and an waveguide.

Hsa-miRNA-23a-3p promotes atherogenesis in a novel mouse model of atherosclerosis.

Of the known regulators of atherosclerosis, miRNAs have been demonstrated to play critical roles in lipoprotein homeostasis and plaque formation. Here, we generated a novel animal model of atherosclerosis by knocking in in C57BL/6 mice, as the W483X mutation in is considered the most common newly identified pathogenic mutation in Chinese familial hypercholesterolemia (FH) individuals. Using the new in vivo mouse model combined with a well-established atherosclerotic in vitro human cell model, we identified a novel atherosclerosis-related miRNA, miR-23a-3p, by microarray analysis of mouse aortic tissue specimens and human aortic endothelial cells (HAECs).

Compact multimode waveguide based temperature-insensitive Mach-Zehnder interferometer.

A novel multimode waveguide based Mach-Zehnder interferometer (MZI) is demonstrated on an SOI platform with the properties of compact footprint and temperature-insensitive operation. The device can achieve a thermal dependence around 13pm/°C in a wavelength range of 40nm. Owing to the utilization of one single straight multimode waveguide, the device is naturally immune to local temperature distributions.

Switch-on fluorescent strategy based on crystal violet-functionalized CdTe quantum dots for detecting L-cysteine and glutathione in water and urine.

The concentration of L-cysteine (Cys) and glutathione (GSH) is closely related to the critical risk of various diseases. In our study, a new rapid method for the determination of Cys and GSH in water and urine samples has been developed using a fluorescent probe technique, which was based on crystal violet (CV)-functionalized CdTe quantum dots (QDs). The original QDs emitted fluorescence light, which was turned off upon adding CV.

Advances in computational approaches in identifying synergistic drug combinations.

Accumulated empirical clinical experience, supported by animal or cell line models, has initiated efforts of predicting synergistic combinatorial drugs with more-than-additive effect compared with the sum of the individual agents. Aiming to construct better computational models, this review started from the latest updated data resources of combinatorial drugs, then summarized the reported mechanism of the known synergistic combinations from aspects of drug molecular and pharmacological patterns, target network properties and compound functional annotation. Based on above, we focused on the main in silico strategies recently published, covering methods of molecular modeling, mathematical simulation, optimization of combinatorial targets and pattern-based statistical/learning model.

Routing light with ultrathin nanostructures beyond the diffraction limit.

An open nanostructure consisting of a periodic chain of subwavelength-nanoparticles for compressing and routing light beyond the diffraction limit is proposed. The open nanostructure is ultrathin and compact, with a size much smaller than the wavelength of light. We demonstrate that our ultrathin open nanostructure provides functions that can route and manipulate light at the subwavelength scale and can also sharply bend and split light beams below the diffraction limit while exhibiting broadband, incident-angle-tolerant, and robust against disorder.

Systemic inoculation of Escherichia coli causes emergency myelopoiesis in zebrafish larval caudal hematopoietic tissue.

Emergency granulopoiesis occurs in response to severe microbial infection. However, whether and how other blood components, particularly monocytes/macrophages and their progenitors, including hematopoietic stem/progenitor cells (HSPCs), participate in the process and the underlying molecular mechanisms remain unknown. In this study, we challenged zebrafish larvae via direct injection of Escherichia coli into the bloodstream, which resulted in systemic inoculation with this microbe.

In Silico Insight into Potential Anti-Alzheimer's Disease Mechanisms of Icariin.

Herbal compounds that have notable therapeutic effect upon Alzheimer's disease (AD) have frequently been found, despite the recent failure of late-stage clinical drugs. Icariin, which is isolated from Epimedium brevicornum, is widely reported to exhibit significant anti-AD effects in in vitro and in vivo studies. However, the molecular mechanism remains thus far unclear.

Functional Cross-Talking between Differentially Expressed and Alternatively Spliced Genes in Human Liver Cancer Cells Treated with Berberine.

Berberine has been identified with anti-proliferative effects on various cancer cells. Many researchers have been trying to elucidate the anti-cancer mechanisms of berberine based on differentially expressed genes. However, differentially alternative splicing genes induced by berberine might also contribute to its pharmacological actions and have not been reported yet.