Nano-Drug Delivery Systems Targeting CAFs: A Promising Treatment for Pancreatic Cancer.

Currently, pancreatic cancer (PC) is one of the most lethal malignant tumors. PC is typically diagnosed at a late stage, exhibits a poor response to conventional treatment, and has a bleak prognosis. Unfortunately, PC's survival rate has not significantly improved since the 1960s. Cancer-associated fibroblasts (CAFs) are a key component of the pancreatic tumor microenvironment (TME). They play a vital role in maintaining the extracellular matrix and facilitating the intricate communication between cancer cells and infiltrated immune cells. Exploring therapeutic approaches targeting CAFs may reverse the current landscape of PC therapy. In recent years, nano-drug delivery systems have evolved rapidly and have been able to accurately target and precisely release drugs with little or no toxicity to the whole body. In this review, we will comprehensively discuss the origin, heterogeneity, potential targets, and recent advances in the nano-drug delivery system of CAFs in PC. We will also propose a novel integrated treatment regimen that utilizes a nano-drug delivery system to target CAFs in PC, combined with radiotherapy and immunotherapy. Additionally, we will address the challenges that this regimen currently faces.

Characterization of the Protective Efficacy Against QX Strain of a Recombinant Infectious Bronchitis Virus With H120 Backbone and QX Spike Gene.

Infectious bronchitis virus (IBV) has been prevalent in chicken farms for many years, and its control relies on extensive vaccine administration. The continuous emergence of new variants and the low cross-protection efficiency prompt the development of new vaccines. In this study, we develop a reverse genetics technique based on the classical vaccine strain H120 genome, via in vitro ligation method. Using the H120 genome as the backbone, we constructed the recombinant virus rH120-QX(S) by replacing the H120 S gene with the QX S gene, a prevalent strain in China. Biological characteristics of the rH120-QX(S) virus, such as 50% egg lethal dose (ELD50), 50% egg infectious dose (EID50), dwarf embryo, growth curve, and genetic stability, are measured, which are comparable to the parental virus H120. There are no clinical symptoms and tissue lesions in the trachea and kidney in the rH120-QX(S)-infected specific-pathogen-free (SPF) chickens, demonstrating that this recombinant virus does not confer pathogenicity. Furthermore, protection studies show that there is 100% homologous protection of rH120-QX(S) to the virulent QX strain, as shown by the absence of clinical signs and no lethality. Taken together, our results demonstrate that swapping the S gene onto the H120 genetic backbone is a precise and effective way to produce genetically defined IBV vaccine candidates.

Implementation of field two-way quantum synchronization of distant clocks across a 7†km deployed fiber link.

The two-way quantum clock synchronization has been shown to provide femtosecond-level synchronization capability and security against symmetric delay attacks, thus becoming a prospective method to compare and synchronize distant clocks with enhanced precision and safety. In this letter, a field test of two-way quantum synchronization between a H-maser and a Rb clock linked by a 7 km-long deployed fiber is implemented by using time-energy entangled photon-pair sources. Limited by the intrinsic frequency stability of the Rb clock, the achieved time stability at 30 s is measured as 32 ps. By applying a fiber-optic microwave frequency transfer technology to build frequency syntonization between the separated clocks, the limit set by the intrinsic frequency stability of the Rb clock is overcome. A significantly improved time stability of 1.9 ps at 30 s is achieved, which is mainly restrained by the low number of acquired photon pairs due to the low sampling rate of the utilized coincidence measurement system. Such implementation demonstrates the high practicability of the two-way quantum clock synchronization method for promoting field applications.

A Compact Laser System for the Pulsed Optically Pumped Rubidium Cell Atomic Clock.

We describe the design and implementation of a compact laser system for the pulsed optically pumped (POP) rubidium (Rb) cell atomic clock. The laser system includes packaged optics for sub-Doppler absorption, acousto-optic modulation and light beam expansion, and dedicated electronics for laser diode reliable single-mode operation and laser frequency stabilization. With beat measurements between two identical laser systems, the laser frequency stability was found to be 3.0×10-12 for averaging times from 1 to 60 s and it reached 3.5×10-12 at 10 000 s averaging time. Based on the compact laser system, the short-term stability of the Rb cell atomic clock in pulsed regime was approximately [Formula: see text], which is in reasonable agreement with the estimated [Formula: see text]. The compact laser system is significant in terms of the development of transportable and high-performance Rb atomic clock prototypes.

The Interplay Between Coronavirus and Type I IFN Response.

In the past few decades, newly evolved coronaviruses have posed a global threat to public health and animal breeding. To control and prevent the coronavirus-related diseases, understanding the interaction of the coronavirus and the host immune system is the top priority. Coronaviruses have evolved multiple mechanisms to evade or antagonize the host immune response to ensure their replication. As the first line and main component of innate immune response, type I IFN response is able to restrict virus in the initial infection stage; it is thus not surprising that the primary aim of the virus is to evade or antagonize the IFN response. Gaining a profound understanding of the interaction between coronaviruses and type I IFN response will shed light on vaccine development and therapeutics. In this review, we provide an update on the current knowledge on strategies employed by coronaviruses to evade type I IFN response.

Microwave Pulse-Coherent Technique-Based Clock With a Novel Magnetron-Type Cavity.

We report a high-performance pulsed optically pumped (POP) Rb clock based on a novel magnetron-type microwave cavity. The cavity has a volume of 30 mL, enabling a highly homogenous microwave field distribution. With the laser frequency tuning to the ground-state hyperfine level F = 2 of the D2 line, we observe a Ramsey fringe contrast of 52% in terms of optical absorption detection. The resultant shot noise limit is estimated to be [Formula: see text]. The clock frequency stability is measured as [Formula: see text] (1-100 s), which is limited by the relative intensity noise of the light.

Quantitative Proteomic Analysis Uncovers the Mediation of Endoplasmic Reticulum Stress-Induced Autophagy in DHAV-1-Infected DEF Cells.

Autophagy is a tightly regulated catabolic process and is activated in cells in response to stress signals. Despite extensive study, the interplay between duck hepatitis A virus type 1 (DHAV-1) and the autophagy of host cells is not clear. In this study, we applied proteomics analysis to investigate the interaction mechanism between DHAV-1 and duck embryo fibroblast (DEF) cells. In total, 507 differentially expressed proteins (DEPs) were identified, with 171 upregulated proteins and 336 downregulated proteins. The protein expression level of heat shock proteins (Hsps) and their response to stimulus proteins and zinc finger proteins (ZFPs) were significantly increased while the same aspects of ribosome proteins declined. Bioinformatics analysis indicated that DEPs were mainly involved in the "response to stimulus", the "defense response to virus", and the "phagosome pathway". Furthermore, Western blot results showed that the conversion of microtubule-associated protein 1 light chain 3-I (LC3-I) to the lipidation form of LC3-II increased, and the conversion rate decreased when DEF cells were processed with 4-phenylbutyrate (4-PBA). These findings indicated that DHAV-1 infection could cause endoplasmic reticulum (ER) stress-induced autophagy in DEF cells, and that ER stress was an important regulatory factor in the activation of autophagy. Our data provide a new clue regarding the host cell response to DHAV-1 and identify proteins involved in the DHAV-1 infection process or the ER stress-induced autophagy process.

Identification and characterization of a novel nanobody against duck hepatitis A virus type 1.

Duck virus hepatitis (DVH) caused by duck hepatitis A virus type 1 (DHAV-1) is an acute and highly contagious disease affecting young ducklings. The VP1 protein is one of the major structural proteins of DHAV-1 carries critical epitopes responsible for the induction of neutralizing antibodies. In this study, we have successfully constructed an immune phage display VHHs library against DHAV-1 with the size of 6 × 106 colonies. A nanobody (Nb) against VP1 protein of DHAV-1, named Nb25, was identified from the immunized phage display library. Nb25 could react with the conserved linear B-cell epitope of 174PAPTST179 in DHAV-1 VP1, even though Nb25 showed no neutralizing activity to DHAV-1. To the best of our knowledge, this is the first report about preparation of anti-DHAV-1 Nbs and identification of the specific conserved linear B-cell epitope of DHAV-1 with Nb, which will facilitate the serologic diagnosis of DHAV-1 infection.