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An efficient borondipyrromethene based near-infrared semiconducting polymer dot with simultaneously narrow absorption and emission bands was designed, and successfully used for selective yellow laser excited cell imaging.

Cancer metastasis is an extremely complex process affected by many factors. An acidic microenvironment can drive cancer cell migration towards blood vessels while also hampering immune cell activity. Here, we identified a mechanism mediated by sialyltransferases that induces an acidic tumor permissive microenvironment (ATPME) in BRCA1-mutant and most BRCA1-low breast cancers. Hypersialylation mediated by ST8SIA4 perturbed the mammary epithelial bilayer structure and generated an ATPME and immunosuppressive microenvironment with increased PD-L1 and PD1 expression. Mechanistically, BRCA1 deficiency increased expression of VEGF-A and IL6 to activate TGFβ-ST8SIA4 signaling. High levels of ST8SIA4 led to accumulation of polysialic acid (PSA) on mammary epithelial membranes that facilitated escape of cancer cells from immunosurveillance, promoting metastasis and resistance to αPD1 treatment. The sialyltransferase inhibitor 3Fax-Peracetyl Neu5Ac neutralized the ATPME, sensitized cancers to immune checkpoint blockade by activating CD8 T cells, and inhibited tumor growth and metastasis. Together, these findings identify a potential therapeutic option for cancers with a high level of PSA.

A novel UiO-66-F4 nanosheet MOFs is reported for piezocatalytic water splitting, realizing a high H2 evolution rate of 178.5 μmol g−1 within 5 h under ultrasonic mechanical vibration (110 W, 40 kHz).

Ultrasound (US)-activated sonodynamic therapy (SDT) stands for a distinct antitumor modality because of its attractive characteristics including intriguing noninvasiveness, desirable safety, and high tissue penetration depth, which, unfortunately, suffers from compromised therapeutic efficacy due to cancer cell-inherent adaptive mechanisms, such as glutathione (GSH) neutralization response to reactive oxygen species (ROS), and glutamine addictive properties of tumors. In this work, we developed a biological sonosensitive platelet (PLT) pharmacytes for favoring US/GSH-responsive combinational therapeutic of glutamine deprivation and augmented SDT. The amino acid transporter SLC6A14 blockade agent α-methyl

The development of high-performance photosensitizers is the top priority in photodynamic therapy (PDT). Iridium complexes are widely used because of their many advantages such as high photostability, long T1 lifetime, high yield of singlet oxygen generation, and so on. Halogen-bridged binuclear complexes are often used as intermediates in the synthesis of photosensitizers but ignored in PDT applications. Here we found that halogen-bridged binuclear iridium complexes showed excellent performance in

Here, we developed a novel, multi-mode superresolution method to perform full-scale structural mapping and measure the energy landscape for single carrier transport along conjugated polymer nanowires. Through quenching of the local emission, the motion of a single photo-generated hole was tracked using blinking-assisted localization microscopy. Then, utilizing binding and unbinding dynamics of quenchers onto the nanowires, local emission spectra were collected sequentially and assembled to create a superresolution map of emission sites throughout the structure. The hole polaron trajectories were overlaid with the superresolution maps to correlate structures with charge transport properties. Using this method, we compared the efficiency of inter- and intra-chain hole transport inside the nanowires and for the first time directly measured the depth of carrier traps originated from torsional disorder and chemical defects.

Cancer phototheranostics in the second near-infrared window (NIR-II, 1000-1700 nm) has recently attracted much attention owing to its high efficacy and good safety compared with that in the first near-infrared window (NIR-I, 650-950 nm). However, the lack of theranostic nanoagents with active-targeting features limits its further application in cancer precision therapies. Herein, we constructed platelet-camouflaged nanoprobes with active-targeting characteristics for NIR-II cancer phototheranostics. The as-prepared biomimetic nanoprobes can not only escape phagocytosis by macrophages but also specifically bind to CD44 on the surface of most cancer cells. We evaluated the active-targeting performance of biomimetic nanoprobes in pancreatic cancer, breast cancer, and glioma mouse models and achieved NIR-II photoacoustic imaging with a high signal-to-background ratio and photothermal treatment with excellent tumor growth inhibition. Our results show the great potential of platelet-camouflaged nanoprobes with NIR-II active-targeting features for cancer precision diagnosis and efficient therapies.

Probe reactivity has long been considered to play a key role in artificial nanochannel sensors, but systematic studies of membrane wettability on detection performance are currently lacking. Inspired by biological aquaporins, we developed an effective strategy to regulate the hydrophilic/hydrophobic balance by the controllable in situ assembly of coordination polymers (CPs) using BDC-NH

Optical imaging and therapy have attracted intense attention due to their high spatial and temporal resolution and mini-invasive and selective features compared to traditional diagnosis and therapy...

Adsorption and photocatalysis are promising strategies to remove pollutants of dyes and antibiotics from wastewater. In this study, we demonstrate a rapid microwave-assisted hydrothermal route for the assembly of 2D copper-porphyrin Metal-Organic Frameworks (Cu-TCPP MOFs) within 1 h. The resulting 2D Cu-TCPP nanosheets with excellent crystallinity and a large surface area (342.72 m2/g) exhibited outstanding adsorption performance for typical dyes with adsorption capacities of about 185 mg/g for rhodamine B, 625 mg/g for methylene blue, and 290 mg/g for Congo red, respectively, as well as for representative antibiotics with adsorption capacities of about 130 mg/g for oxytocin, 150 mg/g for tetracycline, and 50 mg/g for norfloxacin, respectively. Meanwhile, the as-prepared 2D Cu-TCPP showed good photocatalytic degradation activity of pollutants after adsorption under irradiation by visible light, reaching removal efficiencies of 81.2 and 86.3% toward rhodamine B and norfloxacin, respectively. These results demonstrate the promising potential of 2D Cu-TCPP for use in the removal of contaminants from wastewater.

Fluorescence probes in the NIR-IIa region show drastically improved imaging owing to the reduced photon scattering and autofluorescence in biological tissues. Now, NIR-IIa polymer dots (Pdots) are developed with a dual fluorescence enhancement mechanism. First, the aggregation induced emission of phenothiazine was used to reduce the nonradiative decay pathways of the polymers in condensed states. Second, fluorescence quenching was minimized by different levels of steric hindrance to further boost the fluorescence. The resulting Pdots displayed a fluorescence QY of ca. 1.7 % in aqueous solution, suggesting an enhancement of ca. 21 times in comparison with the original polymer in tetrahydrofuran (THF) solution. Small-animal imaging by using the NIR-IIa Pdots exhibited a remarkable improvement in penetration depth and signal to background ratio, as confirmed by through-skull and through-scalp fluorescent imaging of the cerebral vasculature of live mice.

Recently, we discovered the H2S-mediated reductive cleavage of the CC bond, and applied this reaction to design probes for the detection of H2S. To extensively elucidate the structure–reactivity relationship, our current work further investigated the effect of substitutes that connected to the CC bond on the H2S-mediated reductive cleavage, wherein different kinds of electron-withdrawing groups (such as pyridine, bipyridine, terpyridine) and electron donating groups (such as carbazole, N,N-dimethylaniline and phenothiazine) were conjugated to the CC bond of interest. Experimental results and DFT calculations showed that the strength of the electron-donating and withdrawing substitutes could significantly affect the reductive cleavage of the CC bond. Unexpectedly, the reductive cleavage was not influenced by the change of the C(2) and C(3) positions in phenothiazine. On this basis, two probes (NPTZ-P1 and NPTZ-P2) with a C(3)-substituted phenothiazine were thus developed and successfully applied for sensing exogenous H2S in living HeLa cells, which implied their potential in bioimaging. This study provides further understanding on the structure–reactivity relationship of the H2S-mediated reductive cleavage of the CC bond, and is also valuable for exploring new reactions of the CC bond in organic synthesis.

International audience; Ferroptosis, characterized by the accumulation of reactive oxygen species and lipid peroxides, has emerged as an attractive strategy to reverse drug resistance. Of particular interest is the ferroptosis-apoptosis combination therapy for cancer treatment. Herein, we report a nanoplatform for effective co-delivery of the anticancer drug sorafenib (S) and the ferroptosis inducer hemin (H) toward synergistic ferroptosis-apoptosis therapy of advanced hepatocellular carcinoma (HCC) as a proof-of-concept study. Liposome is an excellent delivery system; however, it is not sufficiently responsive to the acidic tumor microenvironment (TME) for tumor-targeted drug delivery. We therefore developed pH-sensitive vesicles (SH-AD-L) by incorporating amphiphilic dendrimers (AD) into liposomes for controlled and pH-stimulated release of sorafenib and hemin in the acidic TME, thanks to the protonation of numerous amine functionalities in AD. Importantly, SH-AD-L not only blocked glutathione synthesis to disrupt the antioxidant system but also increased intracellular Fe2+ and •OH concentrations to amplify oxidative stress, both of which contribute to enhanced ferroptosis. Remarkably, high levels of •OH also augmented sorafenib-mediated apoptosis in tumor cells. This study demonstrates the power and efficacy of the effective ferroptosis-apoptosis combination therapy, as well as the promise of the AD-doped TME-responsive vesicles for drug delivery in combination therapy to treat advanced HCC.

Objectives: The present study assessed the risk factors for cytomegalovirus (CMV) corneal infection and compared the odds ratios.Methods: This study was a retrospective case-control study (2014.12–2021.1) over a 6-year period. We reviewed the medical record data and compared the differences between the CMV-positive and virus-negative groups with regard to sex, age, first diagnosis, and ocular complications to identify factors that may be associated with CMV corneal infections. The risk factors for CMV corneal infection were analysed using the chi-squared test and binary logistic regression models.Results: Ninety CMV-positive cases and 151 virus-negative controls were involved in this study. The risk factors for CMV corneal infection were Stevens-Johnson syndrome ocular complication (OR 12.851, 95%CI, 1.435–111.111; P=0.000), a penetrating keratoplasty (PKP) (OR 4.950, 95%CI, 2.632–9.346; P=0.024, and an anterior lamellar keratoplasty (DALK) (OR 5.290, 95%CI, 1.250–22.222; P=0.022).Conclusion: Severe corneal damage (PKP or DALK) and a severe corneal inflammatory response (SJS ocular complication) may be risk factors for CMV corneal infections.

Pulsed lasers were used extensively in material processing including cutting, drilling and marking. The temporal shape and duration of the pulse were important in optimizing the material processing quality. The flexible parameters of MOPA pulsed fiber laser can offer a broad range of material response characteristics. In this report, a MOPA pulsed fiber laser was configured with pulse duration from 2 to 500 ns and PRF that ranged from single shot to 4000kHz.Pulse energy up to 1mJ to investigate independently the contributions of each of these parameters on the marking process of Si wafer. Various experiments were presented to require the high quality marking on Si wafer. Topography evolution pictures of dot were taken and the depths were measured. Experimental results showed that single pulse energy had a significant influence on the threshold of the visible mark. Pulse numbers had more impact on the dot topography. Pulse energy and pulse duration had more influence on the mark depth. In order to control finely the mark depth, single pulse energy and pulse numbers should be optimized.

The silicon material is very sensitive to the change of the laser, and a small change in energy will cause a relatively large change in the morphology of the mark. Therefore, it is a great challenge to produce uniform and high-quality laser marks on silicon wafers. A new Master Oscillator Power-Amplifier (MOPA) fiber laser with independently adjustable pulse width and frequency have a wide adjustable parameter window. In this paper, a new type of MOPA fiber laser is used to study the marking process on silicon wafers. By changing average power (defined by the active current set point), pulse repetition frequency (PRF) and pulse duration of the laser (i.e., the number of pulses), dot matrix marking on the wafer, using the Keyence VHX-6000 optical microscope to determine the cleanliness and surface topography of the wafer surface to evaluate. Studies have shown that the influence of the output instability of the fiber laser on the marking quality can be reduced by increasing the number of pulses under the condition of stable and low power. At the same time, the resolution of the single pulse energy of the laser is improved by changing the laser PRF, and then the control precision of the energy is improved, so as to realize the high-quality silicon wafer laser marking process with uniform and stable marking morphology.

Peroxymonosulfate (PMS)-based Fenton-like reactions are widely used for wastewater remediation. Metal-free carbonaceous activators can avoid the secondary pollution caused by metal leaching but often suffer from insufficient activity due to limited active centers and mass transfer barriers. Here, we prepared a series of heteroatom (N, S, F)-doped, highly porous carbonaceous materials (UC-X, X = N, S, F) by pyrolyzing UiO-66 precursors assembled by various organic ligands. Density functional theory calculations showed that the heteroatoms modulated the electronic structures of the carbon plane. UC-X exhibited significantly enhanced PMS activation capability compared with the undoped counterpart, in the efficiency order of UC-N > UC-S > UC-F > UC. UC-N (calcined at 1000°C) showed the best PMS activation, exceeding that of commonly used carbocatalysts. The prominent performance of UC-N originated from its unique porous structure and homogeneously dispersed graphitic N moieties. Trapping experiments and electron spin resonance showed a nonradical degradation pathway in the UC-N/PMS system, through which organics were oxidized by donating electrons to UC-N/PMS* metastable complexes. This work not only reports a universal way to access high-performance, metal-free PMS activators but also provides insight into the underlying mechanism of the carbon-activated PMS process.

Three dimensional (3D), two dimensional (2D), and one dimensional (1D) BiOCl catalysts have previously been synthesized and investigated. In this work, for the first time, 6.3-nm or zero dimensional (0D) BiOCl nanoparticles (NPs) and a series of BiOCl samples with different ratios of (001) exposed crystal faces were synthesized via a self-developed vapor-thermal method. Compared with the other samples, the 0D BiOCl possesses a higher ratio of exposed (001) faces, more oxygen vacancies, co-existent Bi+3−x and Bi+3+x, and fewer hydroxyl groups adsorbed to the NPs surface. The surface states result in a red-shift of the light absorption edge, reduced recombination probability, and an increased in the transfer rate for the photo-generated charge carriers. This resulted in an enhanced photocatalytic degradation ability for Rhodamine B (RhB). In addition, the 0D BiOCl exhibits hydrophobicity, while the other samples exhibit hydrophilicity. The proposed method was utilized to synthesize a few different kinds of photocatalysts and their composites with a unique morphology, novel properties, and excellent photocatalytic performance. This method paves the way for further improvements in photocatalytic performances and provides for the possibility of finding novel properties.

Hereditary sensory and autonomic neuropathy Type 1 (HSAN1) is a rare autosomal dominantly inherited neuropathy, clinically characterized by a loss of distal peripheral sensory and motoneuronal function. Mutations in subunits of serine palmitoyltransferase (SPT) have been linked to the majority of HSAN1 cases. SPTs catalyze the condensation of l-serine with palmitoyl-CoA, the first committed and rate-limiting step in de novo sphingolipid biosynthesis. Despite extensive investigation, the molecular pathogenesis of HSAN1 remains controversial. Here, we established a Caenorhabditis elegans (C. elegans) model of HSAN1 by generating a sptl-1(c363g) mutation, encoding SPTL-1(C121W) and equivalent to human SPTLC1(C133W), at the C. elegans genomic locus through CRISPR. The sptl-1(c363g) homozygous mutants exhibited the same larval lethality and epithelial polarity defect as observed in sptl-1(RNAi) animals, suggesting a loss-of-function effect of the SPTL-1(C121W) mutation. sptl-1(c363g)/+ heterozygous mutants displayed sensory dysfunction with concomitant neuronal morphology and axon-dendrite polarity defects, demonstrating that the C. elegans model recapitulates characteristics of the human disease. sptl-1(c363g)-derived neuronal defects were copied in animals with defective sphingolipid biosynthetic enzymes downstream of SPTL-1, including ceramide glucosyltransferases, suggesting that SPTLC1(C133W) contributes to the HSAN1 pathogenesis by limiting the production of complex sphingolipids, including glucosylceramide. Overexpression of SPTL-1(C121W) led to similar epithelial and neuronal defects and to reduced levels of complex sphingolipids, specifically glucosylceramide, consistent with a dominant-negative effect of SPTL-1(C121W) that is mediated by loss of this downstream product. Genetic interactions between SPTL-1(C121W) and components of directional trafficking in neurons suggest that the neuronal polarity phenotype could be caused by glycosphingolipid-dependent defects in polarized vesicular trafficking. SIGNIFICANCE STATEMENT The symptoms of inherited metabolic diseases are often attributed to the accumulation of toxic intermediates or byproducts, no matter whether the disease-causing enzyme participates in a biosynthetic or a degradation pathway. By showing that the phenotypes observed in a C. elegans model of HSAN1 disease could be caused by loss of a downstream product (glucosylceramide) rather than the accumulation of a toxic byproduct, our work provides new insights into the origins of the symptoms of inherited metabolic diseases while expanding the repertoire of sphingolipid functions, specifically, of glucosylceramides. These findings not only have their most immediate relevance for neuroprotective treatments for HSAN1, they may also have implications for a much broader range of neurologic conditions.

Bright long-wavelength-excitable (green and beyond) semiconducting polymer dots (LWE-Pdots) are highly desirable for in vivo fluorescent imaging, as well as applications of multiple- wavelength-excitation based in vitro bioassays. Conventional LWE-Pdots have been obtained previously by incorporating a small amount of near-infrared (NIR) emitter into the backbone of a polymer host to develop a binary donor-acceptor (D-A) system. They usually suffer from severe concentration quenching and a trade-off between fluorescence quantum yield (Φ(f)) and absorption cross-section (σ), limiting the improvement in brightness. In this communication, we describe a ternary component (D(1)/D(2)-A) strategy to achieve ultrabright, green laser (532 nm)-excitable Pdots with narrow-band NIR emission by introducing a BODIPY-based assistant polymer donor as D(1). The novel use of BODIPY as predominant absorber in a Pdot allows strong, narrow-band absorption at 532 nm. The D(1)/D(2)-A Pdots possess simultaneously improved Φ(f) and σ compared to corresponding binary D(2)-A Pdots. Their Φ(f) is as high as 40.2%, one of the most efficient NIR Pdots reported. The ternary D(1)/D(2)-A Pdots show ultrahigh single-particle brightness, ~83 times brighter than Qdot 705 when excited by a 532 nm laser. Intravenously injected Pdots accumulate in implanted tumors in mice through the enhanced permeability and retention effect. Higher contrast in vivo tumor imaging was achieved using the ultrabright ternary Pdots versus the binary D-A Pdots. What’s more, this D(1)/D(2)-A design strategy supplies us a promising way to pursue ultrabright Pdots with even longer absorption and emission.