Single-cell landscape of the ecosystem in early-relapse hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has high relapse and low 5-year survival rates. Single-cell profiling in relapsed HCC may aid in the design of effective anticancer therapies, including immunotherapies. We profiled the transcriptomes of ∼17,000 cells from 18 primary or early-relapse HCC cases. Early-relapse tumors have reduced levels of regulatory T cells, increased dendritic cells (DCs), and increased infiltrated CD8+ T cells, compared with primary tumors, in two independent cohorts. Remarkably, CD8+ T cells in recurrent tumors overexpressed KLRB1 (CD161) and displayed an innate-like low cytotoxic state, with low clonal expansion, unlike the classical exhausted state observed in primary HCC. The enrichment of these cells was associated with a worse prognosis. Differential gene expression and interaction analyses revealed potential immune evasion mechanisms in recurrent tumor cells that dampen DC antigen presentation and recruit innate-like CD8+ T cells. Our comprehensive picture of the HCC ecosystem provides deeper insights into immune evasion mechanisms associated with tumor relapse.

Visible Light-Activated Ultralong-Lived Triplet Excitons of Carbon Dots for White-Light Manipulated Anti-Counterfeiting.

Room temperature phosphorescence (RTP) has emerged as an interesting but rare phenomenon with multiple potential applications in anti-counterfeiting, optoelectronic devices, and biosensing. Nevertheless, the pursuit of ultralong lifetimes of RTP under visible light excitation presents a significant challenge. Here, new phosphorescent materials that can be excited by visible light with record-long lifetimes are demonstrated, realized through embedding nitrogen doped carbon dots (N-CDs) into a poly(vinyl alcohol) (PVA) film. The RTP lifetime of the N-CDs@PVA film is remarkably extended to 2.1 s excited by 420 nm, representing the highest recorded value for visible light-excited phosphorescent materials. Theoretical and experimental studies reveal that the robust hydrogen bonding interactions can effectively reduce the non-radiative decay rate and radiative transition rate of triplet excitons, thus dramatically prolong the phosphorescence lifetime. Notably, the RTP emission of N-CDs@PVA film can also be activated by easily accessible low-power white-light-emitting diode. More significantly, the practical applications of the N-CDs@PVA film in state-of-the-art anti-counterfeiting security and optical information storage domains are further demonstrated. This research offers exciting opportunities for utilizing visible light-activated ultralong-lived RTP systems in a wide range of promising applications.

A prospective study on the wound healing and quality of life outcomes of patients with venous leg ulcers in Singapore-Interim analysis at 6 month follow up.

Venous leg ulceration results in significant morbidity. However, the majority of studies conducted are on Western populations. This study aims to evaluate the wound healing and quality of life for patients with venous leg ulcers (VLUs) in a Southeast Asian population. This is a multi-centre prospective cohort study from Nov 2019 to Nov 2021. All patients were started on 2- or 4-layer compression bandage and were reviewed weekly or fortnightly. Our outcomes were wound healing, factors predictive of wound healing and the EuroQol 5-dimensional 5-level (EQ-5D-5L) health states. Within our cohort, there were 255 patients with VLU. Mean age was 65.2 ± 11.6 years. Incidence of diabetes mellitus was 42.0%. Median duration of ulcer at baseline was 0.30 years (interquartile range 0.136-0.834). Overall, the median time to wound healing was 4.5 months (95% confidence interval [CI]: 3.77-5.43). The incidence of complete wound healing at 3- and 6-month was 47.0% and 60.9%, respectively. The duration of the wound at baseline was independently associated with worse wound healing (Hazard ratio 0.94, 95% CI: 0.89-0.99, P = .014). Patients with healed VLU had a significantly higher incidence of perfect EQ-5D-5L health states at 6 months (57.8% vs 13.8%, P < .001). We intend to present longer term results in subsequent publications.

Ferroelectric polarization effect on the photocatalytic activity of Bi0.9Ca0.1FeO3/CdS S-scheme nanocomposites.

BiFeO3 (BFO), as a kind of narrow band-gap semiconductor material, has gradually emerged advantages in the application of photocatalysis. In this paper, Ca doped BFO nanoparticles Bi0.9Ca0.1FeO3 (BCFO) were prepared by sol-gel method. And BCFO and CdS nanocomposites with two morphologies were obtained by controlling the time of loading CdS under a low temperature liquid phase process. It is found that the band gap becomes narrower after doping Ca into BFO, which is conducive to the absorption of visible light. Among all the samples, the composite of CdS nanowires and BCFO nanoparticles obtained by reaction time of 10 min has the best photocatalytic performance. The degradation rate of Methyl Orange solution was 94% after 90 min under visible light irradiation, which was much higher than that of pure BCFO and CdS. Furthermore, significant enhancement in the degradation rate (100% degradation in 60 min) can be achieved in poled samples after electric polarization process. The highest degradation rate is due to the promoted separation of photogenerated carriers induced by the internal polarization field and the formation of S-scheme heterostructure between BCFO and CdS. Such BCFO-CdS nanocomposites may bring new insights into designing highly efficient photocatalyst.

Spatially Resolved Organic Whispering-Gallery-Mode Hetero-Microrings for High-Security Photonic Barcodes.

Whispering-gallery-mode (WGM) microcavities featuring distinguishable sharp peaks in a broadband exhibit enormous advantages in the field of miniaturized photonic barcodes. However, such kind of barcodes developed hitherto are primarily based on microcavities wherein multiple gain medias were blended into a single matrix, thus resulting in the limited and indistinguishable coding elements. Here, a surface tension assisted heterogeneous assembly strategy is proposed to construct the spatially resolved WGM hetero-microrings with multiple spatial colors along its circular direction. Through precisely regulating the charge-transfer (CT) strength, full-color microrings covering the entire visible range were effectively acquired, which exhibit a series of sharp and recognizable peaks and allow for the effective construction of high-quality photonic barcodes. Notably, the spatially resolved WGM hetero-microrings with multiple coding elements were finally acquired through heterogeneous nucleation and growth controlled by the directional diffusion between the hetero-emulsion droplets, thus remarkably promoting the security strength and coding capacity of the barcodes. The results would be useful to fabricate new types of organic hierarchical hybrid WGM heterostructures for optical information recording and security labels.

Nitrobenzoxadiazole derivatives of the rat selective toxicant norbormide as fluorescent probes for live cell imaging.

Norbormide [5-(α-hydroxy-α-2-pyridylbenzyl)-7-(α-2-pyridylbenzylidene)-5-norbornene-2,3-dicarboximide] (NRB, 1), an existing but infrequently used rodenticide, is known to be uniquely toxic to rats, but relatively harmless to other rodents and mammals. As a vasoactive agent, NRB induces a species-specific vasocontractile effect that is restricted to the peripheral arteries of the rat. Despite the precise mechanisms behind this phenomenon having yet to be fully clarified, it is postulated that the molecular target of NRB could be located within the plasma membrane of rat peripheral artery myocytes (e.g. rat caudal artery myocytes). As such, the primary objective of this study was to develop a fluorescently labelled derivative of NRB to investigate its subcellular distribution/localization in both NRB-sensitive (freshly isolated rat caudal artery myocytes, FIRCAMs) and NRB-insensitive (human hepatic stellate, LX2) cells. Of the examples prepared, lead structure endo-NRB-NBD-bPA subsequently demonstrated retention of the parent toxicant's pharmacological profile (in terms of its ability to induce both a vasocontractile response in rat caudal artery rings in vitro, and a lethal end-point in rats in vivo). Endo-NRB-NBD-bPA was also shown to be significantly less permeable (an integral feature in the design of fluorescent probes targeting cell-surface receptors) to both LX2 cells and FIRCAMs. Disappointingly, no fluorescence could be observed on the plasma membrane of FIRCAMs stained with endo-NRB-NBD-bPA.

Gram-Scale Synthesis of Highly Efficient Rare-Earth-Element-Free Red/Green/Blue Solid-State Bandgap Fluorescent Carbon Quantum Rings for White Light-Emitting Diodes.

The negative impact of rare-earth elements (REEs) on the environment, limited supply and high cost prompt the need for REE-free phosphor-converted white light-emitting diodes (LEDs). Here, we report the gram-scale synthesis of red/green/blue solid-state bandgap fluorescent carbon quantum rings (R/G/B-SBF-CQRs) with high quantum yields up to 30-46 %. This was achieved using cyano-group-bearing p-phenyldiacetonitrile as precursor and forming carbon quantum rings of different diameters through the linkage of curved carbon quantum ribbons of different lengths. The results show the role of cyano groups in inducing the curvature of the carbon quantum ribbons for CQR formation and emission of stable solid-state bandgap fluorescence. R/G/B-SBF-CQRs-phosphor-based LEDs emitted warm white light with low CCT (3576 K), high CRI (96.6), and high luminous efficiency (48.7 lm W-1 ), comparable to REE-phosphor-based LEDs.

Topological-Distortion-Driven Amorphous Spherical Metal-Organic Frameworks for High-Quality Single-Mode Microlasers.

Metal-organic frameworks (MOFs) have recently emerged as appealing platforms to construct microlasers owing to their compelling characters combining the excellent stability of inorganic materials and processable characters of organic materials. However, MOF microstructures developed thus far are generally composed of multiple edge boundaries due to their crystalline nature, which consequently raises significant scattering losses that are detrimental to lasing performance. In this work, we propose a strategy to overcome the above drawback by designing spherically shaped MOFs microcavities. Such spherical MOF microstructures are constructed by amorphizing MOFs with a topological distortion network through introducing flexible building blocks into the growth environment. With an ultra-smooth surface and excellent circular boundaries, the acquired spherical microcavities possess a Q factor as high as ≈104 and can provide sufficient feedback for high-quality single-mode lasing oscillations. We hope that these results will pave an avenue for the construction of new types of flexible MOF-based photonic components.

Laterally Engineering Lanthanide-MOFs Epitaxial Heterostructures for Spatially Resolved Planar 2D Photonic Barcoding.

Metal-organic frameworks (MOFs) heterostructures with domain-controlled emissive colors have shown great potential for achieving high-throughput sensing, anti-counterfeit and information security. Here, a strategy based on steric-hindrance effect is proposed to construct lateral lanthanide-MOFs (Ln-MOFs) epitaxial heterostructures, where the channel-directed guest molecules are introduced to rebalance in-plane and out-of-plane growth rates of the Ln-MOFs microrods and eventually generate lateral MOF epitaxial heterostructures with controllable aspect ratios. A library of lateral Ln-MOFs heterostructures are acquired through a stepwise epitaxial growth procedure, from which rational modulation of each domain with specific lanthanide doping species allows for definition of photonic barcodes in a two-dimensional (2D) domain with remarkably enlarged encoding capacity. The results provide molecular-level insight into the use of modulators in governing crystallite morphology for spatially assembling multifunctional heterostructures.

Spatially Responsive Multicolor Lanthanide-MOF Heterostructures for Covert Photonic Barcodes.

Micro/nanoscale photonic barcodes based on multicolor luminescent segmented heterojunctions hold potential for applications in information security. However, such multicolor heterojunctions reported thus far are exclusively based on static luminescent signals, thus restricting their application in advanced confidential information protection. Reported here is a strategy to design responsive photonic barcodes with heterobimetallic (Tb3+ /Eu3+ ) metal-organic framework multicolor heterostructures. The spatial colors could be precisely controlled by thermally manipulating the energy-transfer process between the two lanthanides, thus achieving responsive covert photonic barcodes. Also demonstrated is that spatially resolved responsive barcodes with multi-responsive features could be created in a single heterostructure. These findings offer unique opportunities to purposely design highly integrated responsive microstructures and smart devices toward advanced anti-counterfeiting applications.

Technique for the measurement of picosecond optical pulses using a non-linear fiber loop mirror and an optical power meter.

A method for measuring picosecond pulse width by using only fiber components and optical power meters is presented. We have shown that the output power splitting ratio of a non-linear fiber loop mirror can be used to extract the full-width half maximum of the optical pulse, assuming a known slowly varying envelope shape and internal phase structure. Theoretical evaluation was carried out using both self-phase and cross-phase modulation approaches, with the latter showing a twofold sensitivity increase, as expected. In the experimental validation, pulses from an actively fiber mode-locked laser at the repetition rate of 10 GHz were incrementally temporally dispersed by using SMF-28 fiber, and then successfully measured over a pulse width range of 2-10 ps, with a resolution of 0.25 ps. This range can be easily extended from 0.25 to 40 ps by selecting different physical setup parameters.

Application of a 2-aryl indenylphosphine ligand in the Buchwald-Hartwig cross-coupling reactions of aryl and heteroaryl chlorides under the solvent-free and aqueous conditions.

An efficient solvent-free protocol for the Buchwald-Hartwig cross-coupling reaction of aryl and heteroaryl chlorides with primary and secondary amines using the Pd(dba)2/ligand 1 catalytic system has been developed. Notably, the catalytic system also efficiently catalyzed the reaction under aqueous conditions.

Promising dawn in tumor microenvironment therapy: engineering oral bacteria.

Despite decades of research, cancer continues to be a major global health concern. The human mouth appears to be a multiplicity of local environments communicating with other organs and causing diseases via microbes. Nowadays, the role of oral microbes in the development and progression of cancer has received increasing scrutiny. At the same time, bioengineering technology and nanotechnology is growing rapidly, in which the physiological activities of natural bacteria are modified to improve the therapeutic efficiency of cancers. These engineered bacteria were transformed to achieve directed genetic reprogramming, selective functional reorganization and precise control. In contrast to endotoxins produced by typical genetically modified bacteria, oral flora exhibits favorable biosafety characteristics. To outline the current cognitions upon oral microbes, engineered microbes and human cancers, related literatures were searched and reviewed based on the PubMed database. We focused on a number of oral microbes and related mechanisms associated with the tumor microenvironment, which involve in cancer occurrence and development. Whether engineering oral bacteria can be a possible application of cancer therapy is worth consideration. A deeper understanding of the relationship between engineered oral bacteria and cancer therapy may enhance our knowledge of tumor pathogenesis thus providing new insights and strategies for cancer prevention and treatment.

A Straightforward, Sensitive, and Reliable Strategy for Ethyl Carbamate Detection in By-Products from Baijiu Production by Enzyme-Linked Immunosorbent Assay.

Baijiu is a renowned Chinese distilled liquor, notable for its distinctive flavor profile and intricate production process, which prominently involves fermentation and distillation. Ethyl carbamate (EC), a probable human carcinogen, can be potentially formed during these procedures, thus prompting significant health concerns. Consequently, the contamination of EC during Baijiu production has become an increasingly pressing issue. In this study, we developed a rapid and easily operable immunoassay for determining EC in the fermented materials used in Baijiu production. The development of a high-quality antibody specific to EC facilitated a streamlined analytical procedure and heightened method sensitivity. Furthermore, we systematically evaluated other essential parameters. Following optimization, the method achieved an IC50 value of 11.83 µg/kg, with negligible cross-reactivity against EC analogs. The recovery study demonstrated the method's good accuracy and precision, with mean recovery rates ranging from 86.0% to 105.5% and coefficients of variation all below 10%. To validate the feasibility of the technique, we collected and analyzed 39 samples simultaneously using both the proposed immunoassay and confirmatory gas chromatography-mass spectrometry (GC-MS). A robust correlation was observed between the results obtained from the two methods (R2 > 0.99). The detected EC levels ranged from 2.36 µg/kg to 7.08 µg/kg, indicating an increase during the fermentation process.

Intelligent onsite dual-modal assay based on oxidase-like fluorescence carbon dots-driven competitive effect for ethyl carbamate detection.

Intelligent onsite accurate monitoring ethyl carbamate (EC, a group 2 A carcinogen) in environment is of great significance to safeguard environmental health and public safety. Herein, we reported an intelligent dual-modal point-of-care (POC) assay based on the bimetallic Mn and Ce co-doped oxidase-like fluorescence carbon dots (Ce&MnCDs) nanozyme-driven competitive effect. In brief, the oxidase-like activity of Ce&MnCDs was inhibited by thiocholine (TCh, originating from the hydrolysis of acetylcholinesterase (AChE) to acetylthiocholine (ATCh)), preventing the oxidation of o-phenylenediamine (OPD) to 2,3-diaminophenothiazine (DAP). However, with the aid of Br2 + NaOH, EC inactivated AChE to prevent TCh generation for re-launching the oxidase-like activity of Ce&MnCDs to trigger the oxidation of OPD into DAP, thereby outputting an EC concentration-dependent ratiometric fluorescence and colorimetric readouts by employing Ce&MnCDs and OPD as the optical signal reporters. Interestingly, these dual-modal optical signals could be transduced into the gray values that was linearly proportional to the residual levels of EC on a smartphone-based portable platform, with a detection limit down to 1.66 µg/mL, qualifying the requirements of analysis of EC residues in real samples. This opened up a new avenue for onsite assessment of the risk of residues of EC, safeguarding environmental health and public safety.

Achieving Bright and Long-Lived Aqueous Room-Temperature Phosphorescence of Carbon Nitrogen Dots Through In Situ Host-Guest Binding.

The development of bright and long-lived aqueous room-temperature phosphorescent (RTP) materials holds paramount importance in broadening the application scope of RTP material system. However, the conventional RTP materials usually exhibit low efficiency and short lifetime in aqueous solution. Herein, an in situ host-guest strategy is proposed to achieve cyanuric acid (CA)-derived phosphorescent carbon nitrogen dots (CNDs) composite (CNDs@CA) that demonstrates a significant enhancement of both quantum yield (QY) and lifetime mediated by water. Detailed investigations reveal that the robust hydrogen bonding networks between CNDs@CA and water effectively stabilize triplet excitons and suppress nonradiative decays, as well as facilitate efficient energy transfer from CA to CNDs, thereby prolonging the lifetime and enhancing the efficiency of RTP. The phosphorescent QY and lifetime of CNDs@CA can be increased to 26.89% (3.9-fold increase) and 951.25 ms (5.5-fold increase), respectively, with the incorporation of 50 wt% water under ambient conditions. Even in fully aqueous environments (with up to 400 wt% water added), CNDs@CA exhibits persistent water-boosted RTP properties, demonstrating exceptional stability. The robust water-boosted RTP property of CNDs@CA in aqueous solutions presents significant potential for high signal-to-noise ratio afterglow bioimaging as well as advanced information encryption.

Cardiovascular disease therapeutics via engineered oral microbiota: Applications and perspective.

Engineering bacteria are considered as a potential treatment for cardiovascular diseases and related risk factors. Oral bacteria are closely related to the occurrence and development of cardiovascular diseases, and their engineering has broad prospects and potential in the treatment of cardiovascular diseases. Oral pathogenic bacteria undergo protein and genetic engineering, including the incorporation of exogenous plasmids to yield therapeutic effects; genetically engineered oral probiotics can be harnessed to secrete cytokines and reactive oxygen species, offering novel therapeutic avenues for cardiovascular diseases.

A Nationwide Survey and Risk Assessment of Ethyl Carbamate Exposure Due to Daily Intake of Alcoholic Beverages in the Chinese General Population.

Ethyl carbamate (EC) is carcinogenic, and, in China, oral intake of EC mainly occurs as a result of the consumption of alcoholic beverages. To obtain the latest EC intake and risk analysis results for the general population in China, the China National Center for Food Safety Risk Assessment (CFSA) conducted the sixth total diet study (TDS) as a platform to analyze EC contents and exposure due to the intake of alcoholic beverages. A total of 100 sites in 24 provinces were involved in the collection and preparation of alcohol mixture samples for the sixth TDS. There were 261 different types of alcohol collected across the country, based on local dietary menus and consumption survey results. Ultimately, each province prepared a mixed sample by mixing their respective samples according to the percentage of local consumption. The EC levels of these twenty-four mixed samples were determined using our well-validated gas chromatography-mass spectrometry (GC-MS) method. The values ranged from 1.0 µg/kg to 33.8 µg/kg, with 10.1 µg/kg being the mean. China's EC daily intake ranged from 0.001 ng/kg bw/d to 24.56 ng/kg bw/d, with a mean of 3.23 ng/kg bw/d. According to the margin of exposure (MOE), virtually safe dose (VSD), and T25 risk assessments of the carcinogenicity of EC, the mean lifetime cancer risk for the Chinese population was 9.8 × 104, 1.5 × 10-7, and 8.6 × 10-8, respectively. These data show that the carcinogenicity of EC in the general Chinese population due to alcoholic intake is essentially minimal.

Facile Preparation of a Multifunctional Hydrogel Composite Dressing via Dual Self-Redox Mechanism for Accelerated Infected Wound Healing.

The management of infected wound healing remains a formidable challenge primarily due to the absence of an ideal wound dressing that can not only effectively inhibit persistent bacterial infection and mitigate excessive inflammation but also possess appropriate mechanical strength, moderate adhesiveness, and favorable self-healability to maintain its protective function and facilitate easy change. In this study, we present an effective strategy for the preparation of a novel composite hydrogel under mild conditions, without the need for additives. This is achieved by incorporating resveratrol (RSV)-loaded alkali lignin nanoparticles (ARNPs) into an advanced polyacrylamide-based hydrogel matrix. The utilization of ARNPs facilitated the sustained release of RSV, thereby enhancing its bioavailability. The polymerization of acrylamide was gently triggered by free radicals generated through a novel dual self-redox mechanism involving silver ions (Ag+), catechols, and ammonium persulfate in neutral and at room temperature, without the requirement of cross-linkers. The dual self-redox reactions played a dominant role in facilitating the gelation process and imparting the desired properties to the resulting hydrogels. The obtained product exhibited exceptional antibacterial properties, favorable anti-inflammatory activity, superior tensile strength, moderate adhesiveness, and reliable self-healability, thereby accelerating the closure of infected wounds. Collectively, this study synergistically integrated RSV-sustained release nanoparticles and a specially designed multifunctional hydrogel into a single system in a conveniently manipulable manner. This composite wound dressing material holds promise for promoting the healing of infected wounds and has potential applications in other complex wound treatments.

Solid-State Fluorescent Carbon Dots with Unprecedented Efficiency from Visible to Near-Infrared Region.

Developing solid-state luminescent materials with bright long-wavelength emissions is of considerable practical importance in light-emitting diodes (LEDs) but remains a formidable challenge. Here, a novel structure engineering strategy is reported to realize solid-state fluorescence (FL)-emitted carbon dots (CDs) from visible to near-infrared region. This is the first report of such an extended wavelength emission of self-quenching-resistant solid-state CDs. Notably, the quantum yields of these CDs are remarkably improved up to 67.7%, which is the highest value for solid-state CDs. The surface polymer chains of CDs can efficiently suppress the conjugated sp2 carbon cores from π-π stacking inducing aggregation caused FL quenching, and the redshift of FL emissions is attributed to narrowing bandgap caused by an enlarged sp2 carbon core. Using these CDs as conversion phosphors, the fabrication of white LEDs with adjustable correlated color temperatures of 1882-5019 K is achieved. Moreover, a plant growth LED device is assembled with a blue-LED chip and deep-red/near-infrared-emitted CDs. Compared with sunlight and white LEDs, the peanuts irradiated by plant growth LED lamp show higher growth efficiency in terms of branches and leaves. This work provides high-quality solid-state CD-based phosphors for LED lighting sources that are required for diverse optoelectronic applications.