A Controlled Release Aptasensor Utilizing AIE-Active MOFs as High-Efficiency ECL Nanoprobe for the Sensitive Detection of Adenosine Triphosphate.

Improving the sensitivity in electrochemiluminescence (ECL) detection systems necessitates the integration of robust ECL luminophores and efficient signal transduction. In this study, we report a novel ECL nanoprobe (Zr-MOF) that exhibits strong and stable emission by incorporating aggregation-induced emission ligands into Zr-based metal-organic frameworks (MOFs). Meanwhile, we designed a high-performance signal modulator through the implementation of a well-designed controlled release system with a self-on/off function. ZnS quantum dots (QDs) encapsulated within the cavities of aminated mesoporous silica nanoparticles (NH2-SiO2) serve as the ECL quenchers, while adenosine triphosphate (ATP) aptamers adsorbed on the surface of NH2-SiO2 through electrostatic interaction act as "gatekeepers." Based on the target-triggered ECL resonance energy transfer between Zr-MOF and ZnS QDs, we establish a coreactant-free ECL aptasensor for the sensitive detection of ATP, achieving an impressive low detection limit of 0.033 nM. This study not only demonstrates the successful combination of ECL with controlled release strategies but also opens new avenues for developing highly efficient MOFs-based ECL systems.

Optical feedback frequency locking: impact of directly reflected field and responding strategies.

The challenges presented by the directly reflected field in optical feedback cavity-enhanced spectroscopy systems serve as substantial obstacles, introducing additional complexity to existing systems and compromising their sensitivity, as the underlying mechanisms of its adverse effects remain not fully understood. This study aims to address this issue by introducing a comprehensive analytical model. Additionally, frequency locking can be achieved by decreasing the feedback rate, the laser's linewidth enhancement factor, and the directly reflected field, and by increasing the refractive index of the gain medium, the length of the laser's resonant cavity, the electric field reflectivity of the laser's output facet, and the resonant field. These parameters can affect the feedback coupling rate pre-factor, and for a resonant cavity with a length of 0.394 m, optical feedback can only be established when the feedback coupling rate pre-factor is less than 1.05 × 109. Through experimental validation, we successfully confirm the effectiveness of the proposed solution in eliminating the detrimental effects of the directly reflected field. Importantly, this suppression is achieved without compromising other aspects of the system's performance. The research findings not only offer the potential to optimize various cavity-enhanced spectroscopy systems that rely on optical feedback but also show promising applications in advancing the development of high-purity spectrum diode lasers utilizing optical feedback from an external high-finesse cavity.

Characterization of the Clinical Significance and Immunological Landscapes of a Novel TMEMs Signature in Hepatocellular Carcinoma and the Contribution of TMEM201 to Hepatocarcinogenesis.

Aberrant transmembrane protein (TMEM) expression is implicated in tumor progression, but its functional role in hepatocellular carcinoma (HCC) is unclear. Thus, we aim to characterize the functional contributions of TMEM in HCC. In this study, four novel TMEM-family genes (TMEMs), TMEM106C, TMEM201, TMEM164, and TMEM45A, were screened to create a TMEMs signature. These candidate genes are distinguished between patients with varying survival statuses. High-risk HCC patients had a significantly worse prognosis and more advanced clinicopathological characteristics in both the training and validation groups. The GO and KEGG analyses unveiled that the TMEMs signature might play a crucial role in cell-cycle-relevant and immune-related pathways. We found that the high-risk patients had lower stromal scores and a more immunosuppressive tumor microenvironment with massive infiltration of macrophages and Treg cells, whereas the low-risk group had higher stromal scores and gamma delta T-cell infiltration. Moreover, the expression level of suppressive immune checkpoints increased as the TMEM-signature scores increased. Furthermore, the in vitro experiments validated TMEM201, one feature of the TMEMs signature, and facilitated HCC proliferation, survival, and migration. The TMEMs signature provided a more precise prognostic evaluation of HCC and reflected the immunological status of HCC. Of the TMEMs signature studied, TMEM201 was found to significantly promote HCC progression.

Combined analysis of imaging tumor capsule with imaging tumor size guides the width of resection margin for solitary hepatocellular carcinoma.

BACKGROUND: The optimal width of resection margin (RM) for hepatocellular carcinoma (HCC) remains controversial. This study aimed to investigate the value of imaging tumor capsule (ITC) and imaging tumor size (ITS) in guiding RM width for patients with HCC. METHODS: Patients who underwent hepatectomy for HCC in our center were retrospectively reviewed. ITC (complete/incomplete) and ITS (≤ 3 cm/> 3 cm) were assessed by preoperative magnetic resonance imaging (MRI). Using subgroup analyses based on ITC and ITS, the impact of RM width [narrow RM (< 5 mm)/wide RM (≥ 5 mm)] on recurrence-free survival (RFS), overall survival (OS), and RM recurrence was analyzed. RESULTS: A total of 247 patients with solitary HCC were included. ITC and ITS were independent predictors for RFS and OS in the entire cohort. In patients with ITS ≤ 3 cm, neither ITC nor RM width showed a significant impact on prognosis, and the incidence of RM recurrence was comparable between the narrow RM and wide RM groups (15.6% vs. 4.3%, P = 0.337). In patients with ITS > 3 cm and complete ITC, the narrow RM group exhibited comparable RFS, OS, and incidence of RM recurrence with the wide RM group (P = 0.606, 0.916, and 0.649, respectively). However, in patients with ITS > 3 cm and incomplete ITC, the wide RM group showed better RFS and OS and a lower incidence of RM recurrence compared with the narrow RM group (P = 0.037, 0.018, and 0.046, respectively). CONCLUSIONS: As MRI-based preoperative markers, conjoint analysis of ITC with ITS aids in determining RM width for solitary HCC patients. Narrow RM is applicable in patients with ITS ≤ 3 cm regardless of ITC status and in those with ITS > 3 cm and complete ITC. Wide RM is preferred in those with ITS > 3 cm and incomplete ITC.

Unimolecular Helix-Based Transmembrane Nanochannel with a Smallest Luminal Cavity of 1 Å Expressing High Proton Selectivity and Transport Activity.

Natural protein channels have evolved with exquisite structures to transport ions selectively and rapidly. Learning from nature to construct biomimetic artificial channels is always challenging. Herein we present a unimolecular transmembrane proton channel by quinoline-derived helix, which exhibited highly selective and ultrafast proton transport behaviors. This helix-based channel possesses a small luminal cavity of 1 Å in diameter, which could efficiently reject the permeation of cations, anions or water molecules but only permits the translocation of protons owing to the size effect. The proton flow rate exceeded 107 H+ s-1 channel-1 and reached the same magnitude with gramicidin A. Mechanism investigation revealed that the directionally arrayed NH-chain inside the synthetic channel played a pivotal role during the proton flux. This work not only presented a helix-based channel with the smallest observable nanopore, but also unveiled an unexplored pathway for realizing efficient transport of protons via the consecutive NH-chain.

Flexible Single-Chain-Heteropolymer-Derived Transmembrane Ion Channels with High K+ Selectivity and Tunable pH-Gated Characteristics.

A series of single-chain random heteropolymer (RHP)-derived artificial ion channels with both high K+ selectivity and controllable pH-gated behaviors were fabricated by a facile "one-pot" polymerization method. The benzo-18-crown-6 moieties appended on lateral chains of RHPs can form ion-permeable nanopores and transport K+ over Na+ through the lipid bilayers. The ion permeation selectivity was significantly enhanced by incorporating a cholesterol group to serve as a membrane anchor. Interestingly, similar to natural gated protein channels, on-off switchable characteristics were also realized by integrating an additional acid-sensitive alkylamine group into the RHP-derived channel. The unique design strategies have endowed the RHP-derived ion channels with facile synthetic procedures, desirable membrane compatibility, high K+ selectivity, and tunable pH-gated properties. This work provides an entry point for future design of novel functional nanochannels.

Template-Free Self-Assembly of Two-Dimensional Polymers into Nano/Microstructured Materials.

In the past few decades, enormous efforts have been made to synthesize covalent polymer nano/microstructured materials with specific morphologies, due to the relationship between their structures and functions. Up to now, the formation of most of these structures often requires either templates or preorganization in order to construct a specific structure before, and then the subsequent removal of previous templates to form a desired structure, on account of the lack of "self-error-correcting" properties of reversible interactions in polymers. The above processes are time-consuming and tedious. A template-free, self-assembled strategy as a "bottom-up" route to fabricate well-defined nano/microstructures remains a challenge. Herein, we introduce the recent progress in template-free, self-assembled nano/microstructures formed by covalent two-dimensional (2D) polymers, such as polymer capsules, polymer films, polymer tubes and polymer rings.

Biomimetic Cascade Polymer Nanoreactors for Starvation and Photodynamic Cancer Therapy.

The selective disruption of nutritional supplements and the metabolic routes of cancer cells offer a promising opportunity for more efficient cancer therapeutics. Herein, a biomimetic cascade polymer nanoreactor (GOx/CAT-NC) was fabricated by encapsulating glucose oxidase (GOx) and catalase (CAT) in a porphyrin polymer nanocapsule for combined starvation and photodynamic anticancer therapy. Internalized by cancer cells, the GOx/CAT-NCs facilitate microenvironmental oxidation by catalyzing endogenous H2O2 to form O2, thereby accelerating intracellular glucose catabolism and enhancing cytotoxic singlet oxygen (1O2) production with infrared irradiation. The GOx/CAT-NCs have demonstrated synergistic advantages in long-term starvation therapy and powerful photodynamic therapy (PDT) in cancer treatment, which inhibits tumor cells at more than twice the rate of starvation therapy alone. The biomimetic polymer nanoreactor will further contribute to the advancement of complementary modes of spatiotemporal control of cancer therapy.

Bioplasmonic paper-based assay for perilipin-2 non-invasively detects renal cancer.

Renal cell carcinoma (RCC) has poor survival prognosis because it is asymptomatic at an early, more curative stage. Recently, urine perilipin-2 (PLIN-2) was demonstrated to be a sensitive and specific biomarker for the noninvasive, early detection of RCC and an indispensable indicator to distinguish cancer from a benign renal mass. However, current Western blot or ELISA PLIN-2 assays are complicated, expensive, time-consuming or insensitive, making them unsuitable for routine analysis in clinical settings. Here we developed a plasmonic biosensor based on the high refractive index sensitivity of gold nanorattles for the rapid detection of PLIN-2 in patient urine. The paper-based plasmonic assay is highly sensitive and has a dynamic range of 50 pg/ml to 5 µg/ml PLIN-2. The assay is not compromised by variations in urine pH or high concentrations of interfering proteins such as albumin and hemoglobin, making it an excellent candidate for routine clinical applications. The urine PLIN-2 assay readily distinguished patients with pathologically proven clear cell carcinomas of various size, stage and grade (55.9 [39.5, 75.8] ng/ml, median [1st and 3rd quartile]) from age-matched controls (0.3 [0.3, 0.5] ng/ml), patients with bladder cancer (0.5 [0.4, 0.6] ng/ml) and patients with diabetic nephropathy (0.6 [0.4, 0.7] ng/ml). Urine PLIN-2 concentrations were roughly proportional to tumor size (Pearson coefficient 0.59). Thus, this cost-effective and label-free method represents a novel approach to conduct a non-invasive population screen or rapid differential diagnosis of imaged renal masses, significantly facilitating the early detection and diagnosis of RCC.

Catalytically Active Bacterial Nanocellulose-Based Ultrafiltration Membrane.

Large quantities of highly toxic organic dyes in industrial wastewater is a persistent challenge in wastewater treatment processes. Here, for highly efficient wastewater treatment, a novel membrane based on bacterial nanocellulose (BNC) loaded with graphene oxide (GO) and palladium (Pd) nanoparticles is demonstrated. This Pd/GO/BNC membrane is realized through the in situ incorporation of GO flakes into BNC matrix during its growth followed by the in situ formation of palladium nanoparticles. The Pd/GO/BNC membrane exhibits highly efficient methylene orange (MO) degradation during filtration (up to 99.3% over a wide range of MO concentrations, pH, and multiple cycles of reuse). Multiple contaminants (a cocktail of 4-nitrophenol, methylene blue, and rhodamine 6G) can also be effectively treated by Pd/GO/BNC membrane simultaneously during filtration. Furthermore, the Pd/GO/BNC membrane demonstrates stable flux (33.1 L m-2 h-1 ) under 58 psi over long duration. The novel and robust membrane demonstrated here is highly scalable and holds a great promise for wastewater treatment.

miR-4775 promotes colorectal cancer invasion and metastasis via the Smad7/TGFß-mediated epithelial to mesenchymal transition.

BACKGROUND: Despite advancements in the diagnosis and treatment of colorectal cancer (CRC), many patients die because of tumor metastasis or recurrence. Therefore, identifying new prognostic markers and elucidating the mechanisms of CRC metastasis and recurrence will help to improve the prognosis of the disease. As dysregulation of microRNAs is strongly related to cancer progression, the aim of this study was to identify the role of miR-4775 in the prognosis of CRC patients and the underling mechanisms involved in CRC progression. METHODS: qPCR and in situ hybridization were used to evaluate the expression of miR-4775 in 544 pairs of paraffin-embedded normal and CRC tissues. Kaplan-Meier analysis with the log-rank test was used for survival analyses. Immunohistochemical staining was applied to investigate the expression of miR-4775-regulated Smad7/TGFß pathway-associated markers. In vitro and in vivo invasion and metastasis assays were used to explore the function of miR-4775 in the progression of CRC. RESULTS: miR-4775 was identified as a high-risk factor for CRC metastasis and recurrence, with high levels predicting poor survival among the 544 studied CRC patients. Furthermore, high miR-4775 expression promoted the invasion of CRC cells as well as metastasis and the epithelial to mesenchymal transition (EMT) via Smad7-mediated activation of TGFß signaling both in vitro and in vivo. Downregulating miR-4775 or overexpressing Smad7 reversed the tumor-promoting roles of miR-4775/Smad7/TGFß in vitro and in vivo. CONCLUSION: miR-4775 promotes CRC metastasis and recurrence in a Smad7/TGFß signaling-dependent manner, providing a new therapeutic target for inhibiting the metastasis or recurrence of the disease.

Silicon photonic physical unclonable function.

Physical unclonable functions (PUFs) serve as a hardware source of private information that cannot be duplicated and have applications in hardware integrity and information security. Here we demonstrate a photonic PUF based on ultrafast nonlinear optical interactions in a chaotic silicon micro-cavity. The device is probed with a spectrally-encoded ultrashort optical pulse, which nonlinearly interacts with the micro-cavity. This interaction produces a highly complex and unpredictable, yet deterministic, ultrafast response that can serve as a unique "fingerprint" of the cavity and as a source of private information for the device's holder. Experimentally, we extract 17.1-kbit binary keys from six different photonic PUF designs and demonstrate the uniqueness and reproducibility of these keys. Furthermore, we experimentally test exact copies of the six photonic PUFs and demonstrate their unclonability due to unavoidable fabrication variations.

Wavelength multicasting through four-wave mixing with an optical comb source.

Based on four-wave mixing (FWM) with an optical comb source (OCS), we experimentally demonstrate 26-way or 15-way wavelength multicasting of 10-Gb/s differential phase-shift keying (DPSK) data in a highly-nonlinear fiber (HNLF) or a silicon waveguide, respectively. The OCS provides multiple spectrally equidistant pump waves leading to a multitude of FWM products after mixing with the signal. We achieve error-free operation with power penalties less than 5.7 dB for the HNLF and 4.2 dB for the silicon waveguide, respectively.

Four-wave mixing Bragg scattering in hydrogenated amorphous silicon waveguides.

We demonstrate 15% on-chip conversion efficiency of four-wave mixing Bragg scattering in a hydrogenated amorphous silicon waveguide with only 55 and 194 mW peak pump powers in the waveguide. The lightwaves can be maintained in the telecommunication band, and the operational bandwidth is measured to be larger than 4 nm.

Pump-degenerate phase-sensitive amplification in amorphous silicon waveguides.

We demonstrate phase-sensitive amplification in hydrogenated amorphous silicon photonic waveguides based on pump-degenerate four-wave mixing at continuous-wave (CW) operation, as well as at repetition rates of both 90 MHz and 10 GHz. At 90 MHz pulsed operation, an 11.7 dB phase-sensitive extinction ratio (ER) is achieved with a peak pump power of 1.6 W. At 10 GHz pulsed operation, a 6.6 dB phase-sensitive ER is achieved with a peak pump power of 0.5 W. At CW operation, a 1.6 dB ER is achieved with a pump power of 38 mW.

Construction of a smart temperature-responsive GPx mimic based on the self-assembly of supra-amphiphiles.

Glutathione peroxidase (GPx) is a major defense against hydroperoxides as a kind of seleno-enzyme that protects cells from oxidative damage. A supramolecular vesicle with controllable GPx activity and morphology has been successfully constructed by the self-assembly of supra-amphiphiles formed by host-guest recognition between cyclodextrin and adamantane derivatives. By introducing thermosensitive poly(N-isopropylacrylamide) (PNIPAM) scaffolds and the catalytic moiety selenium into adamantane and cyclodextrin, respectively, the complex of catalysis-functionalized cyclodextrin with thermosensitivity-functionalized adamantane directed the formation of a supramolecular vesicle which acted as a GPx mimic at 37 °C. The self-assembled nanoenzyme exhibited an obvious temperature responsive characteristic and high GPx-like catalytic activity promoting the reduction of hydrogen peroxide (H2O2) with glutathione (GSH) as the reducing substrate at 37 °C. However, the vesicle disassembled when the temperature decreased to 25 °C due to the transition of PNIPAM between the coil and the globule. Interestingly, the catalytic activity changed along with the transformation of morphologies. The vesicle structure self-assembled at 37 °C provided the favorable microenvironment for the enzymatic reaction, hence we successfully developed a temperature-responsive nanoenzyme model. Moreover, the catalytic activity of the thermosensitive GPx mimic exhibited excellent reversibility and typical saturation kinetics behaviour similar to a natural enzyme catalyst. It is assumed that the proposed GPx model not only has remarkable advantages such as easy functionalization and facile preparation but also provided a new way to develop intelligent responsive materials.

PANoptosis-related molecule CASP2 affects the immune microenvironment and immunotherapy response of hepatocellular carcinoma.

Background: The involvement of molecules associated with PANoptosis in hepatocellular carcinoma (HCC) is still not well understood. Methods: Various R packages were utilized to analyze within the R software. Data that was freely accessible was obtained from the databases of The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC). Results: Here, we comprehensively explored the role of PANoptosis-related genes in HCC. The caspase 2 (CASP2) was identified as the interest gene for further analysis. We found that CASP2 is related to the poor prognosis and worse clinical features of HCC patients. Moreover, we explored the biological pathway CASP2 is involved in and found that CASP2 is associated with multiple carcinogenic pathways. Also, we noticed that CASP2 can significantly reshape the HCC immune microenvironment and affect the response rate of immunotherapy. Analysis of drug sensitivity suggested that individuals exhibiting elevated CASP2 levels may display increased susceptibility to doxorubicin and vorinostat while demonstrating resistance towards erlotinib, lapatinib, sunitinib, and temsirolimus. Meanwhile, we explored the single-cell distribution of CASP2 in the HCC microenvironment. To enhance the clinical application of CASP2 in HCC, we constructed a prognosis model using the molecules derived from CASP2, which demonstrated good efficiency in predicting patients prognosis. Moreover, in vitro experiments indicated that CASP2 can significantly inhibits cell proliferation, invasion and migration ability of HCC cells. Conclusions: Our study comprehensively explored the role of PANoptosis-related molecule CASP2 in HCC, which can provide directions for future studies.

Fighting bacteria with bacteria: A biocompatible living hydrogel patch for combating bacterial infections and promoting wound healing.

Bacterial infections are among the most critical global health challenges that seriously threaten the security of human. To address this issue, a biocompatible engineered living hydrogel patch was developed by co-embedding engineered photothermal bacteria (EM), photosensitizer (porphyrin) and reactive oxygen species amplifier (laccase) in a protein hydrogel. Remarkably, the genetice engineered bacteria can express melanin granules in vivo and this allows them to exhibit photothermal response upon being exposed to NIR-II laser (1064 nm) irradiation. Besides, electrostatically adhered tetramethylpyridinium porphyrin (TMPyP) on the bacterial surface and encapsulated laccase (Lac) in protein gel can generate highly toxic singlet oxygen (1O2) and hydroxyl radical (·OH) in the presence of visible light and lignin, respectively. Interestingly, the engineered bacteria hydrogel patch (EMTL@Gel) was successfully applied in synergistic photothermal, photodynamic and chemodynamic therapy, in which it was able to efficiently treat bacterial infection in mouse wounds and enhance wound healing. This work demonstrates the concept of "fighting bacteria with bacteria" combining bacterial engineering and material engineering into an engineered living hydrogel path that can synergistically boost the therapeutic outcome. STATEMENT OF SIGNIFICANCE: Genetically engineered bacteria produce melanin granules in vivo, exhibiting remarkable photothermal properties. These bacteria, along with a photosensitizer (TMPyP) and a reactive oxygen species amplifier (laccase), are incorporated into a biocompatible protein hydrogel patch. Under visible light, the patch generates toxic singlet oxygen (1O2) and hydroxyl radical (·OH), demonstrates outstanding synergistic effects in photothermal, photodynamic, and chemodynamic therapy, effectively treating bacterial infections and promoting wound healing in mice.

Liquid-Liquid Phase Separation-Mediated Photocatalytic Subcellular Hybrid System for Highly Efficient Hydrogen Production.

Plant chloroplasts have a highly compartmentalized interior, essential for executing photocatalytic functions. However, the construction of a photocatalytic reaction compartment similar to chloroplasts in inorganic-biological hybrid systems (IBS) has not been reported. Drawing inspiration from the compartmentalized chloroplast and the phenomenon of liquid-liquid phase separation, herein, a new strategy is first developed for constructing a photocatalytic subcellular hybrid system through liquid-liquid phase separation technology in living cells. Photosensitizers and in vivo expressed hydrogenases are designed to coassemble within the cell to create subcellular compartments for synergetic photocatalysis. This compartmentalization facilitates efficient electron transfer and light energy utilization, resulting in highly effective H2 production. The subcellular compartments hybrid system (HM/IBSCS) exhibits a nearly 87-fold increase in H2 production compared to the bare bacteria/hybrid system. Furthermore, the intracellular compartments of the photocatalytic reactor enhance the system's stability obviously, with the bacteria maintaining approximately 81% of their H2 production activity even after undergoing five cycles of photocatalytic hydrogen production. The research brings forward visionary prospects for the field of semi-artificial photosynthesis, offering new possibilities for advancements in areas such as renewable energy, biomanufacturing, and genetic engineering.

Prognostic Value of Combined Neutrophil-to-Lymphocyte Ratio and Imaging Tumor Capsule in Solitary Hepatocellular Carcinoma Patients after Narrow-Margin Hepatectomy.

BACKGROUND: The study aimed to investigate the clinical value and prognostic patterns of the neutrophil-to-lymphocyte ratio (NLR) and imaging tumor capsule (ITC) in solitary hepatocellular carcinoma (HCC) patients undergoing narrow-margin hepatectomy. METHODS: Data for solitary HCC patients treated with narrow-margin surgery were extracted from Shanghai General Hospital. Clinical features of recurrence-free survival (RFS), overall survival (OS), and early recurrence were investigated by Cox/logistic regression. The significant variables were subsequently incorporated into the nomogram pattern. Survival analysis stratified by NLR and ITC was also performed. RESULTS: The study included a cohort of 222 patients, with median RFS and OS of 24.083 and 32.283 months, respectively. Both an NLR ≥ 2.80 and incomplete ITC had a significant impact on prognosis. NLR and ITC independently affected RFS and OS, whereas alpha-fetoprotein (AFP) and ITC were identified as independent factors for early relapse. The RFS and OS nomogram, generated based on the Cox model, demonstrated good performance in validation. The combination of NLR and ITC showed greater predictive accuracy for 5-year RFS and OS. Subgroups with an NLR ≥ 2.80 and incomplete ITC had the worst prognosis. CONCLUSIONS: Both NLR and ITC significantly affected RFS, OS, and early recurrence among solitary HCC patients who underwent narrow-margin hepatectomy. The combination of NLR and ITC has the potential to guide rational clinical treatment and determine the prognosis.