Functional Dynamics Inside Nano- or Microscale Bio-Hybrid Systems

Soft nano- or microgels made by natural or synthetic polymers have been investigated intensively because of their board applications. Due to their porosity and biocompatibility, nano- or microgels can be integrated with various biologics to form a bio-hybrid system. They can support living cells as a scaffold; entrap bioactive molecules as a drug carrier or encapsulate microorganisms as a semi-permeable membrane. Especially, researchers have created various modes of functional dynamics into these bio-hybrid systems. From one side, the encapsulating materials can respond to the external stimulus and release the cargo. From the other side, cells can respond to physical, or chemical properties of the matrix and differentiate into a specific cell type. With recent advancements of synthetic biology, cells can be further programed to respond to certain signals, and express therapeutics or other functional proteins for various purposes. Thus, the integration of nano- or microgels and programed cells becomes a potential candidate in applications spanning from biotechnology to new medicines. This brief review will first talk about several nano- or microgels systems fabricated by natural or synthetic polymers, and further discuss their applications when integrated with various types of biologics. In particular, we will concentrate on the dynamics embedded in these bio-hybrid systems, to dissect their designs and sophisticated functions

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

Potential of Core-Collapse Supernova Neutrino Detection at JUNO

JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve

Detection of the Diffuse Supernova Neutrino Background with JUNO

As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO

CAR T cell therapy in advanced B‐ALL with heavy disease burden

Abstract In recent years, CD19‐directed chimeric antigen receptor (CAR) T cell therapy has exhibited significant potency for treating pediatric relapsed or refractory B‐cell acute lymphoblastic leukemia (r/r B‐ALL). Nonetheless, many patients with disease progressing rapidly may not benefit from this therapy. Actually, 10%–20% of these patients with rapidly progressive disease failed in CAR T cell manufacturing. Besides, some patients died of disease progression earlier than CAR T cells expanding in vivo. How to deal with the fast progressive disease and ensure successful manufacturing and expansion of CAR T cells are still very important questions for the clinicians. In this brief report, some clinical experience to handle these tough situations in our center will be introduced. Bridging chemotherapy and post‐CAR antitumor managements help to control progressive blasts and contribute to the success of CAR T cell therapy. The optimal timing of apheresis and adjusted protocol for manufacturing CAR T cells are critical for advanced patients. Optimal treatment options and how they should be applied to advanced B‐ALL with heavy disease burden still need to be discussed

Study on the Status, Problems and Suggestions of the Development of Aquatic Product Industry in Nine Mainland Cities of the Guangdong-Hong Kong-Macao Greater Bay Area

The Guangdong-Hong Kong-Macao Greater Bay Area is located at coastal area of the opening frontier in China, with the Pan-Pearl River Delta region as the vast development hinterland, which is an important support point for the country to implement the innovation-driven development strategy and promote the construction of "The Belt and Road Initiative". By analyzing the current situation and existing problems of aquatic product industry in nine mainland cities of the Guangdong-Hong Kong-Macao Greater Bay Area, the future development trend are judged and important development paths are put forward to promote the high-quality development of aquatic product industry in Greater Bay Area. Nine mainland cities in the Greater Bay Area are the dominant industrial agglomeration areas of aquaculture, especially the freshwater aquaculture in Guangdong Province, accounting for 49.58% and 42.28% of the province's output value and output, respectively, and accounting for more than 50% of the province's freshwater aquaculture area, with outstanding freshwater aquaculture capacity, which is the main area of pond aquaculture in Guangdong Province. Nine mainland cities in the Greater Bay Area have a complete chain of aquatic product industry, a high overall technical level, an advantage in aquatic seedling industry, and a relatively concentrated aquatic product processing and circulation industry. Relying on huge market consumption demand in the Guangdong-Hong Kong-Macao Greater Bay Area, the processing volume of freshwater products, the circulation of aquatic products and the total output value of service industry in nine mainland cities all exceed 50% of the whole province. From the perspective of industrial spatial layout, the aquatic product industry of nine mainland cities in the Greater Bay Area generally radiates from southwest to northeast. Jiangmen and Foshan have made outstanding contributions to the development of seawater and freshwater aquaculture in the Greater Bay Area respectively, while Guangzhou and Foshan are the polarization centers of aquatic fingerlings. At present, there are still some problems in the aquatic product industry of nine mainland cities in the Greater Bay Area, such as insufficient breeding technology, low level of production modernization, great constraints on resources and environment, less intensive processing, industrial supervision to be strengthened, and low degree of industrial integration. In order to promote the high-quality development of aquaculture in nine mainland cities in the Greater Bay Area, this study summarizes the basic path, necessary conditions and core motivation, that is, with optimizing the allocation of essential resources as a basis, improving industrial policy design and strengthening talent allocation and technological innovation to drive aquaculture modernization and green industrial development with science and technology. And concrete measures and suggestions on six aspects are put forward as follows: consolidating industrial foundation, improving supervision ability, promoting industrial integration and development, enhancing brand value, strengthening industrial digital construction and giving full play to the advantages of seedling industry

An atomistic study of copper extrusion in through-silicon-via using phase field crystal models

Three-dimensional system integration using Cu through-silicon-via (TSV) technology enables vertical interconnection of stacked dies. However, the large statistical distribution of plastic Cu extrusion, also known as Cu pumping, presents a serious reliability concern. Traditional finite element method (FEM) based thermo-mechanical modeling that neglects microstructure has been extensively attempted in order to identify the root cause of the extrusion, which yet remains unknown. This study utilizes recently developed phase field crystal (PFC) models, which resolve systems on atomic length scales and diffusive timescales, to capture the creation, destruction, and interaction of defects in polycrystalline Cu TSV structures and thereby elucidate the atomistic mechanisms of the Cu extrusion. The governing kinetic equation of the PFC model is first solved using FEM to generate Cu grains with an atomic resolution in TSVs by referring to experimental EBSD images. A shearing term is then added to the governing equation to simulate TSV deformation under shear strain. The solidification process at the atomistic scale is simulated to prepare polycrystalline TSV samples. Rotation and coalescence of grains with low mis-orientations are observed in solidification. The application of shear strain to the polycrystalline TSVs reveals the movement of defects at the atomistic scale. The defects diffuse through grain boundaries and aggregate at the edges of TSVs, where the defects become immobile. The process of rotation and coalescence of grains is found to be accelerated under the shear strain. The simulation results also suggest that the geometry of the TSVs is an important factor controlling the behavior of defect diffusion and microstructures in TSVs, and thus the mechanical behavior of TSVs

Relationship between patient-perceived quality of primary care and self-reported hospital utilisation in China: A cross-sectional study

AbstractBackground Reducing avoidable hospital admissions is a global healthcare priority, with optimal primary care recognised as pivotal for achieving this objective. However, in developing systems like China, where primary care is evolving without compulsory gatekeeping, the relationship between patient-perceived primary care quality and hospital utilisation remains underexplored.Objectives This study aimed to explore the association between patient-perceived primary care quality and self-reported hospital utilisation in China.Methods Data were collected from 16 primary care settings. Patient-perceived quality of primary care was measured using the Assessment Survey of Primary Care scale across six domains (first-contact care, continuity, comprehensiveness, accessibility, coordination, and patient-centredness). Hospital utilisation included patient self-reported outpatient visits, hospital admissions, and emergency department (ED) visits in the last six months. Logistic regression analyses were examined associations between self-reported hospital utilisation and perceived primary care quality adjusted for potential confounders.Results Of 1,185 patients recruited, 398 (33.6%) reported hospital utilisation. Logistic regression analyses showed that higher total scores for patient-perceived quality of primary care were associated with decreased odds of hospital utilisation (adjusted odds ratio(AOR): 0.417, 95% confidence interval (CI): 0.308–0.565), outpatient visits (AOR: 0.394, 95% CI: 0.275–0.566) and hospital admissions (AOR: 0.496, 95% CI: 0.276–0.891). However, continuity of care was positively associated with ED visits (AOR: 2.252, 95% CI: 1.051–4.825).Conclusion Enhanced patient-perceived quality of primary care in China is associated with a reduction in self-reported overall hospital utilisation, including outpatient visits and hospital admissions. However, better continuity of care may be associated with increased ED visits. Further research is warranted for precise insights and validation of these findings