Twin-field quantum key distribution without optical frequency dissemination

Twin-field (TF) quantum key distribution (QKD) has rapidly risen as the most viable solution to long-distance secure fibre communication thanks to its fundamentally repeater-like rate-loss scaling. However, its implementation complexity, if not successfully addressed, could impede or even prevent its advance into real-world. To satisfy its requirement for twin-field coherence, all present setups adopted essentially a gigantic, resource-inefficient interferometer structure that lacks scalability that mature QKD systems provide with simplex quantum links. Here we introduce a novel technique that can stabilise an open channel without using a closed interferometer and has general applicability to phase-sensitive quantum communications. Using locally generated frequency combs to establish mutual coherence, we develop a simple and versatile TF-QKD setup that does not need service fibre and can operate over links of 100 km asymmetry. We confirm the setup's repeater-like behaviour and obtain a finite-size rate of 0.32 bit/s at a distance of 615.6 km.Comment: 14 pages, 7 figure

Tumor microenvironment in pancreatic ductal adenocarcinoma: Implications in immunotherapy

Pancreatic ductal adenocarcinoma is one of the most aggressive and lethal cancers. Surgical resection is the only curable treatment option, but it is available for only a small fraction of patients at the time of diagnosis. With current therapeutic regimens, the average 5-year survival rate is less than 10% in pancreatic cancer patients. Immunotherapy has emerged as one of the most promising treatment options for multiple solid tumors of advanced stage. However, its clinical efficacy is suboptimal in most clinical trials on pancreatic cancer. Current studies have suggested that the tumor microenvironment is likely the underlying barrier affecting immunotherapy drug efficacy in pancreatic cancer. In this review, we discuss the role of the tumor microenvironment in pancreatic cancer and the latest advances in immunotherapy on pancreatic cancer

Experimental Quantum Communication Overcomes the Rate-loss Limit without Global Phase Tracking

Secure key rate (SKR) of point-point quantum key distribution (QKD) is fundamentally bounded by the rate-loss limit. Recent breakthrough of twin-field (TF) QKD can overcome this limit and enables long distance quantum communication, but its implementation necessitates complex global phase tracking and requires strong phase references which not only add to noise but also reduce the duty cycle for quantum transmission. Here, we resolve these shortcomings, and importantly achieve even higher SKRs than TF-QKD, via implementing an innovative but simpler measurement-device-independent QKD which realizes repeater-like communication through asynchronous coincidence pairing. Over 413 and 508 km optical fibers, we achieve finite-size SKRs of 590.61 and 42.64 bit/s, which are respectively 1.80 and 4.08 times of their corresponding absolute rate limits. Significantly, the SKR at 306 km exceeds 5 kbit/s and meets the bitrate requirement for live one-time-pad encryption of voice communication. Our work will bring forward economical and efficient intercity quantum-secure networks.Comment: 29 pages, 10 figures, 3 table

SATB2 shows different profiles between appendiceal adenocarcinomas ex goblet cell carcinoids and appendiceal/colorectal conventional adenocarcinomas: An immunohistochemical study with comparison to CDX2

Background: Special AT-rich sequence-binding protein 2 (SATB2) is a novel marker for colorectal adenocarcinomas but little is known about its expression in appendiceal adenocarcinomas. We aim to investigate SATB2 in these tumors and colorectal adenocarcinomas with comparison to CDX2. Methods: Immunohistochemical stains for SATB2 and CDX2 were performed in 49 appendiceal adenocarcinomas (23 conventional, 26 adenocarcinoma ex goblet cell carcinoids (AdexGCCs)) and 57 colorectal adenocarcinomas. Their expression was correlated with tumor differentiation and growth patterns. Results: SATB2 staining was positive in 26/26 (100%) appendiceal AdexGCCs and 15/23 (65%) appendiceal conventional adenocarcinomas (P = 0.001). Their mean percentage of SATB2-positive cells was 93% and 34%, respectively (P \u3c 0.0001). CDX2 staining was seen in 26/26 (100%) AdexGCCs and 22/23 (96%) appendiceal conventional adenocarcinomas (P = 0.4694). SATB2 and CDX2 showed similar staining in AdexGCCs but CDX2 labeled more tumor cells than SATB2 in conventional adenocarcinomas (mean 84% vs. 34%, P \u3c 0.0001). SATB2 and CDX2 staining was seen in 82% (47/57) and 96% (55/57) colorectal adenocarcinomas, respectively (P = 0.01). The mean percentage of cells positive for SATB2 and CDX2 was 48% and 91%, respectively (P \u3c 0.00001). Decreased SATB2 immunoreactivity was associated with non-glandular differentiation particularly signet ring cells in colorectal (P = 0.001) and appendiceal conventional adenocarcinomas (P = 0.04) but not in appendiceal AdexGCCs. Conclusions: SATB2 is a highly sensitive marker for appendiceal AdexGCCs with similar sensitivity as CDX2. In colorectal and appendiceal conventional adenocarcinomas, SATB2 is not as sensitive as CDX2 and its immunoreactivity is dependent on tumor differentiation

A facile and general approach for the synthesis of fluorescent silica nanoparticles doped with inert dyes

A general and facile approach was developed for the synthesis of almost monodisperse fluorescent silica nanoparticles (NPs) doped with inert dyes, which are organic fluorophores that are strongly fluorescent but are hydrophobic or lack a covalent binding group. The prepared NPs were mesoporous and the dye molecules were encapsulated in the pores via hydrophobic interaction with the CTAB template. The NPs were stable and highly fluorescent in aqueous solution, and have potential applications in bioanalysis and fluorescence encoding.National Natural Science Foundation of China[20875079, 20835005]; Planned Science and Technology Project of Xiamen, China[3502z20080011]; Specialized Research Fund for the Doctoral Program of Higher Education of China[200803840007

Molecule-scale controlled-release system based on light-responsive silica nanoparticles

We report a molecule-scale controlled-release system based on silica nanoparticles bearing a photoactive o-nitrobenzyl bromide linkage, which allows cage and release of drug or biologically active molecules by light

Light-responsive nanogated ensemble based on polymer grafted mesoporous silica hybrid nanoparticles

Mesoporous silica nanoparticles grafted with light-responsive polymer on the outer surface were developed as novel nanogated ensembles, which allow encapsulation and release of drug and biological molecules under light irradiation.National Natural Science Foundation of China [20875079, 20835005]; Planned Science and Technology Project of Xiamen, China [3502z20080011]; Specialized Research Fund for the Doctoral Program of Higher Education of China [200803840007

Light-triggered covalent assembly of gold nanoparticles in aqueous solution

UV light irradiation triggers Au NPs that are respectively functionalized on the surface by o-nitrobenzyl alcohol and benzylamine to proceed with a covalent ligation reaction, which leads to assembling of Au NPs into anisotropic one-dimensional (1D) arrays in aqueous solution via indazolone linkages.National Natural Science Foundation of China[20875079, 20835005]; The Planned Science and Technology Project of Xiamen, China[3502z20080011]; Specialized Research Fund for Doctoral Program of Higher Education of China[200803840007

Fluorescent core-shell silica nanoparticles as tunable precursors: towards encoding and multifunctional nano-probes

Core-shell silica nanoparticles comprised of a RuBpy doped silica core and a Pas-DTPA doped silica shell were synthesized and post-functionalized with an encoding fluorescence combination and multiplex imaging function

A Randomized, Double-Blind, Phase 2b Proof-of-Concept Clinical Trial in Early Alzheimer’s Disease With Lecanemab, an Anti-aβ Protofibril Antibody

Background: Lecanemab (BAN2401), an IgG1 monoclonal antibody, preferentially targets soluble aggregated amyloid beta (Aβ), with activity across oligomers, protofibrils, and insoluble fibrils. BAN2401-G000-201, a randomized double-blind clinical trial, utilized a Bayesian design with response-adaptive randomization to assess 3 doses across 2 regimens of lecanemab versus placebo in early Alzheimer’s disease, mild cognitive impairment due to Alzheimer’s disease (AD) and mild AD dementia. Methods: BAN2401-G000-201 aimed to establish the effective dose 90% (ED90), defined as the simplest dose that achieves ≥90% of the maximum treatment effect. The primary endpoint was Bayesian analysis of 12-month clinical change on the Alzheimer’s Disease Composite Score (ADCOMS) for the ED90 dose, which required an 80% probability of ≥25% clinical reduction in decline versus placebo. Key secondary endpoints included 18-month Bayesian and frequentist analyses of brain amyloid reduction using positron emission tomography; clinical decline on ADCOMS, Clinical Dementia Rating-Sum-of-Boxes (CDR-SB), and Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog14); changes in CSF core biomarkers; and total hippocampal volume (HV) using volumetric magnetic resonance imaging. Results: A total of 854 randomized subjects were treated (lecanemab, 609; placebo, 245). At 12 months, the 10-mg/kg biweekly ED90 dose showed a 64% probability to be better than placebo by 25% on ADCOMS, which missed the 80% threshold for the primary outcome. At 18 months, 10-mg/kg biweekly lecanemab reduced brain amyloid (−0.306 SUVr units) while showing a drug-placebo difference in favor of active treatment by 27% and 30% on ADCOMS, 56% and 47% on ADAS-Cog14, and 33% and 26% on CDR-SB versus placebo according to Bayesian and frequentist analyses, respectively. CSF biomarkers were supportive of a treatment effect. Lecanemab was well-tolerated with 9.9% incidence of amyloid-related imaging abnormalities-edema/effusion at 10 mg/kg biweekly. Conclusions: BAN2401-G000-201 did not meet the 12-month primary endpoint. However, prespecified 18-month Bayesian and frequentist analyses demonstrated reduction in brain amyloid accompanied by a consistent reduction of clinical decline across several clinical and biomarker endpoints. A phase 3 study (Clarity AD) in early Alzheimer’s disease is underway. Trial registration: Clinical Trials.govNCT01767311