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Keratoconus, a disorder characterized by corneal thinning and weakening, results in vision loss. Corneal crosslinking (CXL) can halt the progression of keratoconus. The development of accelerated corneal crosslinking (A-CXL) protocols to shorten the treatment time has been hampered by the rapid depletion of stromal oxygen when higher UVA intensities are used, resulting in a reduced cross-linking effect. It is therefore imperative to develop better methods to increase the oxygen concentration within the corneal stroma during the A-CXL process. Photocatalytic oxygen-generating nanomaterials are promising candidates to solve the hypoxia problem during A-CXL. Biocompatible graphitic carbon nitride (g-C3N4) quantum dots (QDs)-based oxygen self-sufficient platforms including g-C3N4 QDs and riboflavin/g-C3N4 QDs composites (RF@g-C3N4 QDs) have been developed in this study. Both display excellent photocatalytic oxygen generation ability, high reactive oxygen species (ROS) yield, and excellent biosafety. More importantly, the A-CXL effect of the g-C3N4 QDs or RF@g-C3N4 QDs composite on male New Zealand white rabbits is better than that of the riboflavin 5'-phosphate sodium (RF) A-CXL protocol under the same conditions, indicating excellent strengthening of the cornea after A-CXL treatments. These lead us to suggest the potential application of g-C3N4 QDs in A-CXL for corneal ectasias and other corneal diseases. NCOMMS-23-46799C Keratoconus can be effectively stabilized by corneal crosslinking (CXL), but the depletion of stromal oxygen limits the efficiency of CXL photochemical reactions. Here the authors address this issue by developing biocompatible graphitic carbon nitride quantum dots- based oxygen self-sufficient platforms. [ABSTRACT FROM AUTHOR]

Nanothermometers enable the detection of temperature changes at the microscopic scale, which is crucial for elucidating biological mechanisms and guiding treatment strategies. However, temperature monitoring of micron-scale structures in vivo using luminescent nanothermometers remains challenging, primarily due to the severe scattering effect of biological tissue that compromises the imaging resolution. Herein, a lanthanide luminescence nanothermometer with a working wavelength beyond 1500 nm is developed to achieve high-resolution temperature imaging in vivo. The energy transfer between lanthanide ions (Er3+ and Yb3+) and H2O molecules, called the environment quenching assisted downshifting process, is utilized to establish temperature-sensitive emissions at 1550 and 980 nm. Using an optimized thin active shell doped with Yb3+ ions, the nanothermometer’s thermal sensitivity and the 1550 nm emission intensity are enhanced by modulating the environment quenching assisted downshifting process. Consequently, minimally invasive temperature imaging of the cerebrovascular system in mice with an imaging resolution of nearly 200 μm is achieved using the nanothermometer. This work points to a method for high-resolution temperature imaging of micron-level structures in vivo, potentially giving insights into research in temperature sensing, disease diagnosis, and treatment development.The strong scattering of biological tissue causes challenges when monitoring temperature changes at the microscale. Here, the authors propose a nanothermometer based on lanthanide luminescence, enabling minimally invasive imaging of the cerebrovascular system of mice at nearly 200 μm resolution. [ABSTRACT FROM AUTHOR]

The dense stroma of desmoplastic tumor limits nanotherapeutic penetration and hampers the antitumor immune response. Here, we report a denaturation-and-penetration strategy and the use of tin monosulfide nanoparticles (SnSNPs) as nano-sonosensitizers that can overcome the stromal barrier for the management of desmoplastic triple-negative breast cancer (TNBC). SnSNPs possess a narrow bandgap (1.18 eV), allowing for efficient electron (e−)-hole (h+) pair separation to generate reactive oxygen species under US activation. More importantly, SnSNPs display mild photothermal properties that can in situ denature tumor collagen and facilitate deep penetration into the tumor mass upon near-infrared irradiation. This approach significantly enhances sonodynamic therapy (SDT) by SnSNPs and boosts antitumor immunity. In mouse models of malignant TNBC and hepatocellular carcinoma (HCC), the combination of robust SDT and enhanced cytotoxic T lymphocyte infiltration achieves remarkable anti-tumor efficacy. This study presents an innovative approach to enhance SDT and antitumor immunity using the denaturation-and-penetration strategy, offering a potential combined sono-immunotherapy approach for the cancer nanomedicine field. The dense stroma of desmoplastic tumor limits nanotherapeutic penetration and hampers the antitumor immune response. Here the authors use tin monosulfide nanoparticles as nano-sonosensitizers to overcome the stromal barrier in triple negative breast cancer and improve the efficacy of sonodynamic therapy and boost antitumor immunity. [ABSTRACT FROM AUTHOR]

An ultrasensitive luminol electrochemiluminescence (ECL) immunosensor was constructed for the detection of prostate specific antigen (PSA) using glucose oxidase–decorated hemin-graphene oxide-gold nanoflowers ternary nanocomposites as probes. Graphene oxide was first modified with hemin and then with gold nanoflowers through an in situ growth method, which has significantly boosted the catalytic activity of this graphene oxide–based peroxidase mimetics. The biocatalytical activity of this ECL immunosensor was thoroughly investigated to achieve selective recognition of the analyte molecules (PSA) by specific binding between antigens and antibodies. The limit of detection was calculated to be 0.32 pg mL−1 with a signal-to-noise ratio of 3. A broad linear range from 7.5 × 10−4 to 2.5 ng mL−1 was obtained. Such step-by-step assembled biosensor showed controlled nanostructure and exhibited promising application in analysis of human serum samples with a recovery range of 90.6–111.8% and a RSD range of 3.9–5.5%. [ABSTRACT FROM AUTHOR]

Sensors, as one of the crucial components of wearable electronics, have attracted much attention due to their extensive application in healthcare, human–machine interfaces, electronic skins (E-skins), rehabilitation, and internet of things. However, there is still a challenge to fabricate flexible strain sensors with both good sensitivity and large working strain range. Herein, a facile, scalable, and low-cost strategy is developed to prepare highly sensitive strain sensors based on natural rubber foam and Ti3C2Tx nanosheeets (MXene/NR) by dip-coating method. The fabricated MXene/NR composite exhibits excellent strain sensitivity and large strain range. The gage factor of the MXene/NR composite reaches 14 in the strain range of 0–5% with a low pressure limitation of detection (435 Pa). Additionally, the sensing range is as large as 0–80% of strain and shows good stability during the pressing and relaxing cycles. It is demonstrated that the MXene/NR composite could be used to detect motions, such as finger pressing and step monitoring, suggesting it is a promising candidate for fabricating wearable electronics. [ABSTRACT FROM AUTHOR]

The modulation of intracellular reactive oxygen species (ROS) levels is crucial for cellular homeostasis and determination of cellular fate. A sublethal level of ROS sustains cell proliferation, differentiation and promotes tumor metastasis, while a drastic ROS burst directly induces apoptosis. Herein, surface-oxidized arsenene nanosheets (As/AsxOy NSs) with type II heterojunction are fabricated with efficient ·O2− and 1O2 production and glutathione consumption through prolonging the lifetime of photo-excited electron-hole pairs. Moreover, the portion of AsxOy with oxygen vacancies not only catalyzes a Fenton-like reaction, generating ·OH and O2 from H2O2, but also inactivates main anti-oxidants to cut off the "retreat routes" of ROS. After polydopamine (PDA) and cancer cell membrane (M) coating, the engineered As/AsxOy@PDA@M NSs serve as an intelligent theranostic platform with active tumor targeting and long-term blood circulation. Given its narrow-band-gap-enabled in vivo fluorescence imaging properties, As/AsxOy@PDA@M NSs could be applied as an imaging-guided non-invasive and real-time nanomedicine for cancer therapy. Multifunctional materials with a number of effects are important for dealing with the complex environment in cancer therapy. Here, the authors report on surface-oxidized arsenene nanosheets coated with polydopamine and cancer cell membrane as a multi theranostic tumour targeting cancer therapy. [ABSTRACT FROM AUTHOR]

Clay-based nanomaterials, especially 2:1 aluminosilicates such as vermiculite, biotite, and illite, have demonstrated great potential in various fields. However, their characteristic sandwiched structures and the lack of effective methods to exfoliate two-dimensional (2D) functional core layers (FCLs) greatly limit their future applications. Herein, we present a universal wet-chemical exfoliation method based on alkali etching that can intelligently "capture" the ultrathin and biocompatible FCLs (MgO and Fe2O3) sandwiched between two identical tetrahedral layers (SiO2 and Al2O3) from vermiculite. Without the sandwich structures that shielded their active sites, the obtained FCL nanosheets (NSs) exhibit a tunable and appropriate electron band structure (with the bandgap decreased from 2.0 eV to 1.4 eV), a conductive band that increased from −0.4 eV to −0.6 eV, and excellent light response characteristics. The great properties of 2D FCL NSs endow them with exciting potential in diverse applications including energy, photocatalysis, and biomedical engineering. This study specifically highlights their application in cancer theranostics as an example, potentially serving as a prelude to future extensive studies of 2D FCL NSs. Clay-based nanomaterials are of wide interest but problems extracting the 2D functional core layers have limited potential applications. Here, the authors report on the wet exfoliation of vermiculite by alkali etching to obtain the core layers and explore the application of the materials in cancer theranostics. [ABSTRACT FROM AUTHOR]

Highlights: 2D Sn nanosheets (SnNSs) were prepared through the combination of cryogenic exfoliation and liquid-phase exfoliation. The functionalized 2D SnNSs have good stability, superior biocompatibility, high photothermal conversion efficiency, and multimode imaging capability.Stanene (Sn)-based materials have been extensively applied in industrial production and daily life, but their potential biomedical application remains largely unexplored, which is due to the absence of the appropriate and effective methods for fabricating Sn-based biomaterials. Herein, we explored a new approach combining cryogenic exfoliation and liquid-phase exfoliation to successfully manufacture two-dimensional (2D) Sn nanosheets (SnNSs). The obtained SnNSs exhibited a typical sheet-like structure with an average size of ~ 100 nm and a thickness of ~ 5.1 nm. After PEGylation, the resulting PEGylated SnNSs (SnNSs@PEG) exhibited good stability, superior biocompatibility, and excellent photothermal performance, which could serve as robust photothermal agents for multi-modal imaging (fluorescence/photoacoustic/photothermal imaging)-guided photothermal elimination of cancer. Furthermore, we also used first-principles density functional theory calculations to investigate the photothermal mechanism of SnNSs, revealing that the free electrons in upper and lower layers of SnNSs contribute to the conversion of the photo to thermal. This work not only introduces a new approach to fabricate 2D SnNSs but also establishes the SnNSs-based nanomedicines for photonic cancer theranostics. This new type of SnNSs with great potential in the field of nanomedicines may spur a wave of developing Sn-based biological materials to benefit biomedical applications. [ABSTRACT FROM AUTHOR]

Premature ovarian failure (POF) is a refractory disease for clinical treatment with the goal of restoring fertility. In this study, umbilical cord mesenchymal stem cells on a collagen scaffold (collagen/UC-MSCs) can activate primordial follicles in vitro via phosphorylation of FOXO3a and FOXO1. Transplantation of collagen/UC-MSCs to the ovaries of POF patients rescued overall ovarian function, evidenced by elevated estradiol concentrations, improved follicular development, and increased number of antral follicles. Successful clinical pregnancy was achieved in women with POF after transplantation of collagen/UC-MSCs or UC-MSCs. In summary, collagen/UC-MSC transplantation may provide an effective treatment for POF. [ABSTRACT FROM AUTHOR]

Paper-based chips (PB-chips; also referred to as lab-on-paper chips) are using patterned paper as a substrate in a lab-on-a-chip platform. They represent an outstanding technique for fabrication of analytical devices for multiplex analyte assays. Typical features include low-cost, portability, disposability and small sample consumption. This review (with 211 refs.) gives a comprehensive and critical insight into current trends in terms of materials and techniques for use in fabrication, modification and detection. Following an introduction into the principles of PB-chips, we discuss features of using paper in lab-on-a-chip devices and the proper choice of paper. We then discuss the versatile methods known for fabrication of PB-chips (ranging from photolithography, plasma treatment, inkjet etching, plotting, to printing including flexographic printing). The modification of PB-chips with micro- and nano-materials possessing superior optical or electronic properties is then reviewed, and the final section covers detection techniques (such as colorimetry, electrochemistry, electrochemiluminescence and chemiluminescence) along with specific (bio)analytical examples. A conclusion and outlook section discusses the challenges and future prospectives in this field. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Medroxyprogesterone (MP) is an anabolic steroid, and its use is forbidden in livestock production. To enforce this ban, it is necessary to develop a highly specific and accurate enzyme-linked immunosorbent assay (ELISA) to detect MP residue. Herein, we describe the first synthesis of a specific hapten which retains the specific structure of MP by replacing the hydroxy group of MP with bromoacetic acid. This MP hapten was conjugated with bovine serum albumin and used as the immunogen in ELISA. The monoclonal antibody was produced by cell fusion. An indirect competitive ELISA was developed based on the monoclonal antibody for the detection of MP, which had a half inhibition concentration of 0.06 ng/mL and a limit of detection of 0.01 ng/mL. No cross-reactivity was found with eight analogous compounds by this method, which showed high specificity for MP. Recoveries ranged from 81 to 88 %, indicating the suitability of this ELISA for MP analysis in food samples. [ABSTRACT FROM AUTHOR]

In this study, the modification of basal planes of highly oriented pyrolytic graphite (HOPG) electrodes with pyrene-functionalised biotin (PFB), via π-π stacking, and ethylene glycol antifouling molecules, via covalent bonding, for detection of streptavidin is presented. Biotin was first conjugated to the pyrene moieties by an esterification reaction in order to enable the self-assembly of biotin onto the surface of HOPG via non-covalent π-π stacking. The as-prepared biotinylated electrode was used as the sensing probe to analyze the concentration of streptavidin via the diminution in pyrene electrochemistry resulted from the desorption of pyrene from the surface that is mediated by the biotin-streptavidin recognition. X-ray photoelectron spectroscopy (XPS), cyclic voltammetry (CV), square wave voltammetry (SWV) measurements, and electrochemical impedance spectroscopy (EIS) were used to characterize the amount of surface bound pyrene modified biotin and the concentration of streptavidin. This simple strategy can be applied to the detection of other biomolecules via bio-recognition and the reversible π-π stacking process. [ABSTRACT FROM AUTHOR]

Deficiency or mutation in the p53 tumor suppressor gene commonly occurs in human cancer and can contribute to disease progression and chemotherapy resistance. Currently, although the pro-survival or pro-death effect of autophagy remains a controversial issue, increasing data seem to support the idea that autophagy facilitates cancer cell resistance to chemotherapy treatment. Here we report that 5-FU treatment causes aberrant autophagosome accumulation in HCT116 p53−/− and HT-29 cancer cells. Specific inhibition of autophagy by 3-MA, CQ or small interfering RNA treatment targeting Atg5 or Beclin 1 can potentiate the re-sensitization of these resistant cancer cells to 5-FU. In further analysis, we show that JNK activation and phosphorylation of Bcl-2 are key determinants in 5-FU-induced autophagy. Inhibition of JNK by the compound SP600125 or JNK siRNA suppressed autophagy and phosphorylation of c-Jun and Bcl-2 but increased 5-FU-induced apoptosis in both HCT116 p53−/− and HT29 cells. Taken together, our results suggest that JNK activation confers 5-FU resistance in HCT116 p53−/− and HT29 cells by promoting autophagy as a pro-survival effect, likely via inducing Bcl-2 phosphorylation. These results provide a promising strategy to improve the efficacy of 5-FU-based chemotherapy for colorectal cancer patients harboring a p53 gene mutation. [ABSTRACT FROM AUTHOR]

The Huangshui River, an important tributary in the upper reaches of the Yellow River, has been regarded as a mother river which gestates Qinghai civilization in China. This paper presents the results of hydrogen and oxygen isotopic and water chemical analyses for the summer and winter Huangshui River water to study its seasonal recharge and major dissolved solutes. Characteristics of hydrogen and oxygen isotopes suggest that precipitation in the Qilian Mountains is the original recharge of the Huangshui River. However, in winter, the basic flow of the Huangshui River only depends on spring recharge and spring water originates from melt and infiltration of bottom layer glaciers. In summer, besides spring water, much rainfall directly recharges the Huangshui River, thus making its flux increase greatly. Water chemistry shows that the processes affecting dissolved solutes in the Huangshui River are also different between summer and winter. In summer, major ions in the river water are dominantly derived from carbonate and evaporate dissolution and anthropogenic inputs. In winter, carbonate dissolution decreases greatly while anthropogenic inputs play a much more important role for dissolved solutes in the river. Hence, further measures should be taken to lay stress on the winter Huangshui River water in order to protect the environment of the Huangshui River and reduce effects of dissolved solutes on, or prevent their pollution toward the upper Yellow River. Moreover, some measures also need to be introduced to prevent the possibility of water eutrophication caused by agricultural activities or stock raising in summer. [ABSTRACT FROM AUTHOR]

Editor's Note: this Article has been retracted; the Retraction Note is available at https://doi.org/10.1038/s41598-021-82870-5. [ABSTRACT FROM AUTHOR]