Ultrasmall copper nanoclusters as an efficient antibacterial agent for primary peritonitis therapy.

The urgent need to develop biocompatible, non-resistant antibacterial agents to effectively combat Gram-negative bacterial infections, particularly for the treatment of peritonitis, presents a significant challenge. In this study, we introduce our water-soluble Cu30 nanoclusters (NCs) as a potent and versatile antibacterial agent tailored for addressing peritonitis. The as-synthesized atomically precise Cu30 NCs demonstrate exceptional broad-spectrum antibacterial performance, and especially outstanding bactericidal activity of 100% against Gram-negative Escherichia coli (E. coli). Our in vivo experimental findings indicate that the Cu30 NCs exhibit remarkable therapeutic efficacy against primary peritonitis caused by E. coli infection. Specifically, the treatment leads to a profound reduction of drug-resistant bacteria in the peritoneal cavity of mice with peritonitis by more than 5 orders of magnitude, along with the resolution of pathological features in the peritoneum and spleen. Additionally, comprehensive in vivo biosafety assessment underscores the remarkable biocompatibility, low biotoxicity, as well as efficient hepatic and renal clearance of Cu30 NCs, emphasizing their potential for in vivo application. This investigation is poised to advance the development of novel Cu NC-based antibacterial agents for in vivo antibacterial treatment and the elimination of abdominal inflammation.

Vascular smooth muscle-specific LRRC8A knockout ameliorates angiotensin II-induced cerebrovascular remodeling by inhibiting the WNK1/FOXO3a/MMP signaling pathway.

Hypertensive cerebrovascular remodeling involves the enlargement of vascular smooth muscle cells (VSMCs), which activates volume-regulated Cl- channels (VRCCs). The leucine-rich repeat-containing family 8 A (LRRC8A) has been shown to be the molecular identity of VRCCs. However, its role in vascular remodeling during hypertension is unclear. In this study, we used vascular smooth muscle-specific LRRC8A knockout (CKO) mice and an angiotensin II (Ang II)-induced hypertension model. The results showed that cerebrovascular remodeling during hypertension was ameliorated in CKO mice, and extracellular matrix (ECM) deposition was reduced. Based on the RNA-sequencing analysis of aortic tissues, the level of matrix metalloproteinases (MMPs), such as MMP-9 and MMP-14, were reduced in CKO mice with hypertension, which was further verified in vivo by qPCR and immunofluorescence analysis. Knockdown of LRRC8A in VSMCs inhibited the Ang II-induced upregulation of collagen I, fibronectin, and matrix metalloproteinases (MMPs), and overexpression of LRRC8A had the opposite effect. Further experiments revealed an interaction between with-no-lysine (K)-1 (WNK1), which is a "Cl--sensitive kinase", and Forkhead transcription factor O3a (FOXO3a), which is a transcription factor that regulates MMP expression. Ang II induced the phosphorylation of WNK1 and downstream FOXO3a, which then increased the expression of MMP-2 and MMP-9. This process was inhibited or potentiated when LRRC8A was knocked down or overexpressed, respectively. Overall, these results demonstrate that LRRC8A knockout in vascular smooth muscle protects against cerebrovascular remodeling during hypertension by reducing ECM deposition and inhibiting the WNK1/FOXO3a/MMP signaling pathway, demonstrating that LRRC8A is a potential therapeutic target for vascular remodeling-associated diseases such as stroke.

A near-infrared fluorescent probe based FRET for ratiometric sensing of H2O2 and viscosity in live cells.

Hydrogen peroxide (H2O2) and viscosity play vital roles in the cellular environment as signaling molecule and microenvironment parameter, respectively, and are associated with many physiological and pathological processes in biological systems. We developed a near-infrared fluorescent probe, CQ, which performed colorimetric and ratiometric detection of H2O2 and viscosity based on the FRET mechanism, and was capable of monitoring changes in viscosity and H2O2 levels simultaneously through two different channels. Based on the specific reaction of H2O2 with borate ester, CQ exhibited a significant ratiometric response to H2O2 with a large Stokes shift of 221 nm, a detection limit of 0.87 µM, a near-infrared emission wavelength of 671 nm, a response time of 1 h, a wide detection ranges of 0.87-800 µM and a high energy transfer efficiency of 99.9 %. CQ could also recognize viscosity by the TICT mechanism, and efficiently detect viscosity changes caused by food thickeners. More importantly, CQ could successfully detect endogenous/exogenous H2O2 and viscosity in live HeLa cells, which was expected to be a practical tool for detecting H2O2 and viscosity in live cells.

A highly sensitive ratiometric fluorescent probe for detecting HSO3-/SO32- and viscosity change based on FRET/TICT mechanism.

BACKGROUND: Sulfur dioxide (SO2) is a significant gas signaling molecule in organisms, and viscosity is a crucial parameter of the cellular microenvironment. They are both involved in regulating many physiological processes in the human body. However, abnormalities in SO2 and viscosity levels are associated with various diseases, such as cardiovascular disease, lung cancer, respiratory diseases, neurological disorders, diabetes and Alzheimer's disease. Hence, it is essential to explore novel and efficient fluorescent probes for simultaneously monitoring SO2 and viscosity in organisms. RESULTS: We selected quinolinium salt with good stability, high fluorescence intensity, good solubility and low cytotoxicity as the fluorophore and developed a highly sensitive ratiometric probe QQD to identify SO2 and viscosity changes based on Förster resonance energy transfer/twisted intramolecular charge transfer (FRET/TICT) mechanism. Excitingly, compared with other probes for SO2 detection, QQD not only identified HSO3-/SO32- with a large Stokes shift (218 nm), low detection limit (1.87 µM), good selectivity, high energy transfer efficiency (92 %) and wide recognition range (1.87-200 µM), but also identified viscosity with a 26-fold fluorescence enhancement and good linearity. Crucially, QQD was applied to detect HSO3-/SO32- and viscosity in actual water and food samples. In addition, QQD had low toxicity and good photostability for imaging HSO3-/SO32- and viscosity in cells. These results confirmed the feasibility and reliability of QQD for HSO3-/SO32- and viscosity imaging and environmental detection. SIGNIFICANCE: We reported a unique ratiometric probe QQD for detecting HSO3-/SO32- and viscosity based on the quinolinium skeleton. In addition to detecting HSO3-/SO32- and viscosity change in actual water and food samples, QQD could also monitor the variations of HSO3-/SO32- and viscosity in cells, which provided an experimental basis for further exploration of the role of SO2 derivatives and viscosity in biological systems.

Functional differentiation and genetic diversity of rice cation exchanger (CAX) genes and their potential use in rice improvement.

Cation exchanger (CAX) genes play an important role in plant growth/development and response to biotic and abiotic stresses. Here, we tried to obtain important information on the functionalities and phenotypic effects of CAX gene family by systematic analyses of their expression patterns, genetic diversity (gene CDS haplotypes, structural variations, gene presence/absence variations) in 3010 rice genomes and nine parents of 496 Huanghuazhan introgression lines, the frequency shifts of the predominant gcHaps at these loci to artificial selection during modern breeding, and their association with tolerances to several abiotic stresses. Significant amounts of variation also exist in the cis-regulatory elements (CREs) of the OsCAX gene promoters in 50 high-quality rice genomes. The functional differentiation of OsCAX gene family were reflected primarily by their tissue and development specific expression patterns and in varied responses to different treatments, by unique sets of CREs in their promoters and their associations with specific agronomic traits/abiotic stress tolerances. Our results indicated that OsCAX1a and OsCAX2 as general signal transporters were in many processes of rice growth/development and responses to diverse environments, but they might be of less value in rice improvement. OsCAX1b, OsCAX1c, OsCAX3 and OsCAX4 was expected to be of potential value in rice improvement because of their associations with specific traits, responsiveness to specific abiotic stresses or phytohormones, and relatively high gcHap and CRE diversity. Our strategy was demonstrated to be highly efficient to obtain important genetic information on genes/alleles of specific gene family and can be used to systematically characterize the other rice gene families.

Anti-Inflammatory and α-Glucosidase Inhibitory Triterpenoid with Diverse Carbon Skeletons from the Fruits of Rosa roxburghii.

The fruits of Rosa roxburghii Tratt. are edible nutritional food with high medicinal value and have been traditionally used as Chinese folk medicine for a long time. In this study, 26 triterpenoids including four new pentacyclic triterpenoids, roxbuterpenes A-D (1, 4, 5, and 24), along with 22 known analogues (2, 3, 6-23, 25, and 26), were isolated from the fruits of R. roxburghii. Their chemical structures were determined on the basis of extensive spectroscopic analyses (including IR, HRESIMS and NMR spectroscopy). The absolute configuration of roxbuterpene A (1) was determined by an X-ray crystallographic analysis. This is the first report of the crystal structure of 5/6/6/6/6-fused system pentacyclic triterpenoid. Notably, roxbuterpenes A and B (1 and 4) possessed the A-ring contracted triterpenoid and nortriterpenoid skeletons with a rare 5/6/6/6/6-fused system, respectively. Compounds 1-7, 11, 13-15, 18-20, 24, and 25 exhibited moderate or potent inhibitory activities against α-glucosidase. Compounds 2, 4, 6, 11, and 14 showed strong activities against α-glucosidase with IC50 values of 8.4 ± 1.6, 7.3 ± 2.2, 13.6 ± 1.4, 0.9 ± 0.4, and 12.5 ± 2.4 µM, respectively (positive control acarbose, 10.1 ± 0.8 µM). Compounds 13, 14, and 16 moderately inhibited the release of NO (nitric oxide) with IC50 values ranging from 25.1 ± 2.0 to 51.4 ± 3.1 µM. Furthermore, the expressions of TNF-α (tumor necrosis factor-α) and IL-6 (interleukin-6) were detected by ELISA (enzyme-linked immunosorbent assay), and compounds 13, 14, and 16 exhibited moderate inhibitory effects on TNF-α and IL-6 release in a dose-dependent manner ranging from 12.5 to 50 µM.

Proteomic study of vitreous in proliferative diabetic retinopathy patients after treatment with aflibercept: a quantitative analysis based on 4D label-free technique.

AIM: To identify different metabolites, proteins and related pathways to elucidate the causes of proliferative diabetic retinopathy (PDR) and resistance to anti-vascular endothelial growth factor (VEGF) drugs, and to provide biomarkers for the diagnosis and treatment of PDR. METHODS: Vitreous specimens from patients with diabetic retinopathy were collected and analyzed by Liquid Chromatography-Mass Spectrometry (LC-MS/MS) analyses based on 4D label-free technology. Statistically differentially expressed proteins (DEPs), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway representation and protein interactions were analyzed. RESULTS: A total of 12 samples were analyzed. The proteomics results showed that a total of 58 proteins were identified as DEPs, of which 47 proteins were up-regulated and 11 proteins were down-regulated. We found that C1q and tumor necrosis factor related protein 5 (C1QTNF5), Clusterin (CLU), tissue inhibitor of metal protease 1 (TIMP1) and signal regulatory protein alpha (SIRPα) can all be specifically regulated after aflibercept treatment. GO functional analysis showed that some DEPs are related to changes in inflammatory regulatory pathways caused by PDR. In addition, protein-protein interaction (PPI) network evaluation revealed that TIMP1 plays a central role in neural regulation. In addition, CD47/SIRPα may become a key target to resolve anti-VEGF drug resistance in PDR. CONCLUSION: Proteomic analysis is an approach of choice to explore the molecular mechanisms of PDR. Our data show that multiple proteins are differentially changed in PDR patients after intravitreal injection of aflibercept, among which C1QTNF5, CLU, TIMP1 and SIRPα may become targets for future treatment of PDR and resolution of anti-VEGF resistance.

Narrow-linewidth and low RIN Tm/Ho co-doped fiber laser based on self-injection locking.

A narrow-linewidth and low relative intensity noise (RIN) Tm/Ho co-doped fiber laser based on a saturable absorber and self-injection locking was demonstrated for the first time. Utilizing self-injection locking technology, the frequency noise power spectral density is remarkably reduced by more than 17.1 dB from 1.21 × 106 Hz2/Hz to 7.30 × 103 Hz2/Hz when the frequency is approximately 1 kHz. Furthermore, a laser with a linewidth compressed to a quarter of the original linewidth from 44.386 kHz to 2.850 kHz, a RIN of less than -127.74 dB/Hz, and an optical signal-to-noise ratio of more than 71.6 dB can be obtained. Using a delay fiber, the relaxation oscillation peak frequencies move to lower frequencies, from 27.9 kHz to 15.8 kHz. The proposed laser is highly competitive in advanced coherent light detection fields, including coherent Doppler wind lidar, high-speed coherent optical communication, and precise absolute distance coherent measurement.

Modulation of Nucleation and Growth Kinetics of Perovskite Nanocrystals Enables Efficient and Spectrally Stable Pure-Red Light-Emitting Diodes.

Perovskite light-emitting diodes (PeLEDs) based on CsPb(Br/I)3 nanocrystals (NCs) usually suffer from severe spectral instability under operating voltage due to the poor-quality PeNCs. Herein, zeolite was utilized to prepare high-quality CsPb(Br/I)3 NCs via promoting the homogeneous nucleation and growth and suppressing the Ostwald ripening of PeNCs. In addition, the decomposed zeolite interacted strongly with PeNCs through Pb-O bonds and hydrogen bonds, which inhibited the formation of defects and suppressed halide ion migration, leading to an improved photoluminescence quantum yield (PLQY) and enhanced stability of PeNCs. Moreover, the strong binding affinity of decomposed zeolite to PeNCs contributed to the formation of homogeneous perovskite films with high PLQY. As a result, pure-red PeLEDs with Commission International de I'Eclairage (CIE) coordinates of (0.705, 0.291) were fabricated, approaching the Rec. 2020 red primary color. The devices achieved a peak external quantum efficiency of 23.0% and outstanding spectral stability.

Lipase in-situ immobilized in covalent organic framework: Enzymatic properties and application in the preparation of 1, 3-dioleoyl-2-palmitoylglycerol.

In this study, the critical importance of designing an appropriate immobilized carrier and method for free lipase to ensure exceptional biological catalytic activity and stability was emphasized. Covalent organic frameworks (COF-1) were synthesized as a novel porous carrier with an azine structure (-CN-NC-) through the condensation of hydrazine hydrate and benzene-1,3,5-tricarbaldehyde at room temperature. Simultaneously, Rhizomucor miehei lipase (RML) was immobilized within the COF-1 carrier using an in-situ aqueous phase method. Characterization of the carrier and RML@COF-1 and evaluation of the lipase properties of RML and RML@COF-1 through p-Nitrophenyl palmitate hydrolysis were conducted. Additionally, application in the synthesis of 1, 3-dioleoyl-2-palmitoylglycerol (OPO) was explored. The results showed that RML@COF-1 exhibited a high enzymatic loading of 285.4 mg/g. Under 60℃ conditions, the activity of RML@COF-1 was 2.31 times higher than that of free RML, and RML@COF-1 retained 77.25% of its original activity after 10 cycles of repeated use, indicating its excellent thermal stability and repeatability. Under the optimal conditions (10%, 1:8 PPP/OA, 45℃, 5 h), the yield of OPO reached 47.35%, showcasing the promising application prospects of the novel immobilized enzyme synthesized via in-situ aqueous phase synthesis for OPO preparation.

Metabolomics-Guided Discovery of New Dimeric Xanthones from Co-Cultures of Mangrove Endophytic Fungi Phomopsis asparagi DHS-48 and Phomopsis sp. DHS-11.

The co-culture strategy, which mimics natural ecology by constructing an artificial microbial community, is a useful tool for the activation of biosynthetic gene clusters (BGCs) to generate new metabolites, as well as to increase the yield of respective target metabolites. As part of our project aiming at the discovery of structurally novel and biologically active natural products from mangrove endophytic fungi, we selected the co-culture of a strain of Phomopsis asparagi DHS-48 with another Phomopsis genus fungus DHS-11, both endophyted in mangrove Rhizophora mangle considering the impart of the taxonomic criteria and ecological data. The competition interaction of the two strains was investigated through morphology observation and scanning electron microscopy (SEM), and it was found that the mycelia of the DHS-48 and DHS-11 compacted and tangled with each other with an interwoven pattern in the co-culture system. A new approach that integrates HPLC chromatogram, 1HNMR spectroscopy, UPLC-MS-PCA, and molecular networking enabled the targeted isolation of the induced metabolites, including three new dimeric xanthones phomoxanthones L-N (1-3), along with six known analogs (4-9). Their planar structures were elucidated by an analysis of their HRMS, MS/MS, and NMR spectroscopic data and the absolute configurations based on ECD calculations. These metabolites showed broad cytotoxic activity against the cancer cells assessed, of which compounds 7-9 displayed significant cytotoxicity towards human liver cells HepG-2 with IC50 values ranging from 4.83 µM to 12.06 µM. Compounds 1-6 exhibited weak immunosuppressive activity against the proliferation of ConA-induced (T-cell) and LPS-induced (B-cell) murine splenic lymphocytes. Therefore, combining co-cultivation with a metabolomics-guided strategy as a discovery tool will be implemented as a systematic strategy for the quick discovery of target bioactive compounds.

Simultaneous photoacoustic and ultrasound imaging: A review.

Photoacoustic imaging (PAI) is an emerging biomedical imaging technique that combines the advantages of optical and ultrasound imaging, enabling the generation of images with both optical resolution and acoustic penetration depth. By leveraging similar signal acquisition and processing methods, the integration of photoacoustic and ultrasound imaging has introduced a novel hybrid imaging modality suitable for clinical applications. Photoacoustic-ultrasound imaging allows for non-invasive, high-resolution, and deep-penetrating imaging, providing a wealth of image information. In recent years, with the deepening research and the expanding biomedical application scenarios of photoacoustic-ultrasound bimodal systems, the immense potential of photoacoustic-ultrasound bimodal imaging in basic research and clinical applications has been demonstrated, with some research achievements already commercialized. In this review, we introduce the principles, technical advantages, and biomedical applications of photoacoustic-ultrasound bimodal imaging techniques, specifically focusing on tomographic, microscopic, and endoscopic imaging modalities. Furthermore, we discuss the future directions of photoacoustic-ultrasound bimodal imaging technology.

Erythrocyte Membrane Camouflaged Nanotheranostics for Optical Molecular Imaging-Escorted Self-Oxygenation Photodynamic Therapy.

Hypoxic tumor microenvironment (TME) hampers the application of oxygen (O2 )-dependent photodynamic therapy (PDT) in solid tumors. To address this problem, a biomimetic nanotheranostics (named MMCC@EM) is developed for optical molecular imaging-escorted self-oxygenation PDT. MMCC@EM is synthesized by encapsulating chlorin e6 (Ce6) and catalase (CAT) in metal-organic framework (MOF) nanoparticles with erythrocyte membrane (EM) camouflage. Based on the biomimetic properties of EM, MMCC@EM efficiently accumulates in tumor tissues. The enriched MMCC@EM achieves TME-activatable drug release, thereby releasing CAT and Ce6, and this process can be monitored through fluorescence (FL) imaging. In addition, endogenous hydrogen peroxide (H2 O2 ) will be decomposed by CAT to produce O2 , which can be reflected by the measurement of intratumoral oxygen concentration using photoacoustic (PA) imaging. Such self-oxygenation nanotheranostics effectively mitigate tumor hypoxia and improve the generation of singlet oxygen (1 O2 ). The 1 O2 disrupts mitochondrial function and triggers caspase-3-mediated cellular apoptosis. Furthermore, MMCC@EM triggers immunogenic cell death (ICD) effect, leading to an increased infiltration of cytotoxic T lymphocytes (CTLs) into tumor tissues. As a result, MMCC@EM exhibits good therapeutic effects in 4T1-tumor bearing mice under the navigation of FL/PA duplex imaging.

Synthesis and pharmacological activity of vinpocetine derivatives.

Vinpocetine and its derivatives were extensively employed in the treatment of ischemic stroke, serving as effective cerebrovascular vasodilators. They could also be utilized for neuroprotection, anti-inflammatory purposes, anti-aging interventions, insomnia treatment, and antidepressant effects. However, due to issues such as hepatic first-pass effect, low bioavailability, and poor patient compliance with multiple dosing, the secondary development of Vinpocetine to address these limitations became a prominent area of research. Five primary methodologies were employed for the synthesis of Vinpocetine derivatives. These included substitution on the A ring to modify the 14-ester group, alteration of the 16-ethyl group, simplification of the D and E rings, and modification of the conformation of Vinpocetine. This paper summarized the current synthesis and activity studies of Vinpocetine and its derivatives, with the aim of providing a reference for the discovery of more potent derivatives of Vinpocetine.

Curcumin and silver nanoparticles loaded antibacterial multifunctional pectin/gelatin films for food packaging applications.

Renewable biomass-based materials have a huge potential to replace petroleum-based products in food packaging. Herein, pectin/gelatin films loaded with curcumin and silver nanoparticles (AgNPs) are prepared by solution-pouring technology to serve as antimicrobial multifunctional food packaging films. AgNPs and curcumin are found to equally distribute in the films. Fourier transform infrared spectroscopy (FT-IR) reveal the hydrogen bonding and electrostatic interaction among curcumin, AgNPs, pectin and gelatin. The composite films show good antioxidant activity, mechanical performance, hydrophobicity and antibacterial ability. The films of P-GCA 0.5 showed 99.57 ± 0.16 % and 100 % inhibition against E. coli and S. aureus, respectively. The films also demonstrate excellent water vapor barrier qualities. In addition, the composite films possess pH-responsive color change behaviors from yellow (pH 3-8) to light red (pH 8-9) to dark red (pH 11-12), which is suitable for monitoring the freshness of shrimp packaging based on pH changes during deterioration process. As sustainable biomass-based materials, the multifunctional composite films are promising in intelligent food packaging applications.

Local-field engineering in slot waveguide for fabricating on-chip Bragg grating filters with high reflectivity across a flat broadband.

On-chip Bragg gratings with high reflectivities have been found to have widespread applications in filters, resonators, and semiconductor lasers. However, achieving strong Bragg reflections with flat response across a broad bandwidth on the popular 220 nm silicon-on-insulator (SOI) platform still remains a challenge. In this paper, such a high performance device is proposed and fabricated, which is based on a slot waveguide with gratings etched on the inner sidewalls of the slot. By manipulating the local field in the slot region using a chirped and tapered grating-based mode transition, the device achieves a flat response with ultra-high reflection and low transmission for the TE mode across a broad operating bandwidth. Leveraging the ultra-high birefringence of the SOI waveguide, the device functions both as a TE slot waveguide reflector and a TM pass polarizer. Simulation results demonstrate that the device exhibits an ultra-high rejection of more than 50 dB and a reflectivity exceeding 0.99 for the TE mode across a 91 nm wavelength range, while maintaining a high transmittance of larger than 0.98 for the TM mode. Experimental results validate that the device performance is consistent with the simulation results. A fabricated device based on such a gratings exhibits a low insertion loss (<0.8 dB) and high polarization extinction ratio (>30 dB) over 100 nm bandwidth (1484 nm-1584 nm), demonstrating that the performance of the present design is competitive with that of the state-of-the-art SOI Bragg gratings.

Human chorionic gonadotrophin indirectly activates peripheral γδT cells to produce interleukin-10 during early pregnancy.

BACKGROUNDS: The immunomodulatory properties of human chorionic gonadotrophin (hCG) have been identified to be critical for successful pregnancy. However, the effects of hCG on peripheral γδT cells during early pregnancy have not been reported previously. METHODS: We cocultured the purified γδT cells and peripheral blood mononuclear cells (PBMCs) with early pregnancy-relevant hCG concentrations and investigated the changes in the immune functional characteristics of γδT cells via flow cytometry assays. RESULTS: The ratios of CD69+ and IL-10+ γδT cells were increased in early pregnant women compared to nonpregnant women. γδT cells expressed low levels of the mannose receptor (CD206) instead of the classical hCG/LH receptor for hCG. The direct treatment of purified γδT cells with early pregnancy-relevant hCG concentrations may have no significant effects on their immune functions. Interestingly, when PBMCs were treated with the same broad range of hCG concentrations, the ratios of CD69+ and IL-10+ γδT cells to total γδT cells were significantly increased. CONCLUSION: Certain early pregnancy-relevant hCG concentrations could enhance the ratios of peripheral CD69+ and IL-10+ γδT cells, contributing to the activation of γδT cells and immunological tolerance during early pregnancy. However, these affects may not be strongly mediated by direct ligand-receptor interactions and they may highly depend on immune microenvironment. Our novel observations propose a perspective into the endocrine-immune dialog that exists between the fetus and maternal immune cells.

A ratiometric fluorescent probe based on the FRET platform for the detection of sulfur dioxide derivatives and viscosity.

BACKGROUND: Sulfur dioxide (SO2) is a common gaseous pollutant that significantly threatens environmental pollution and human health. Meanwhile, viscosity is an essential parameter of the intracellular microenvironment, manipulating many physiological roles such as nutrient transport, metabolism, signaling regulation and apoptosis. Currently, most of the fluorescent probes used for detecting SO2 derivatives and viscosity are single-emission probes or probes based on the ICT mechanism, which suffer from short emission wavelengths, small Stokes shifts or susceptibility to environmental background. Therefore, the development of powerful high-performance probes for real-time monitoring of sulfur dioxide derivatives and viscosity is of great significance for human health. RESULTS: In this research, we designed the fluorescent probe QQC to detect SO2 derivatives and viscosity based on FRET platform with quinolinium salt as donor and quinolinium-carbazole as acceptor. QQC exhibited a ratiometric fluorescence response to SO2 with a low detection limit (0.09 µM), large Stokes shift (186 nm) and high energy transfer efficiency (95 %), indicating that probe QQC had good sensitivity and specificity. In addition, QQC was sensitive to viscosity, with an 9.10-folds enhancement of orange fluorescence and an excellent linear relationship (R2 = 0.98) between the logarithm of fluorescence intensity at 592 nm and viscosity. Importantly, QQC could not only recognize SO2 derivatives in real water samples and food, but also detect viscosity changes caused by food thickeners and thereby had broad market application prospects. SIGNIFICANCE: We have developed a ratiometric fluorescent probe based on the FRET platform for detecting sulfur dioxide derivatives and viscosity. QQC could not only successfully detect SO2 derivatives in food and water samples, but also be made into test strips for detecting HSO3-/SO32- solution. In addition, the probe was also used to detect viscosity changes caused by food thickeners. Therefore, this novel probe had significant value in food and environmental detection applications.

CFATransUnet: Channel-wise cross fusion attention and transformer for 2D medical image segmentation.

Medical image segmentation faces current challenges in effectively extracting and fusing long-distance and local semantic information, as well as mitigating or eliminating semantic gaps during the encoding and decoding process. To alleviate the above two problems, we propose a new U-shaped network structure, called CFATransUnet, with Transformer and CNN blocks as the backbone network, equipped with Channel-wise Cross Fusion Attention and Transformer (CCFAT) module, containing Channel-wise Cross Fusion Transformer (CCFT) and Channel-wise Cross Fusion Attention (CCFA). Specifically, we use a Transformer and CNN blocks to construct the encoder and decoder for adequate extraction and fusion of long-range and local semantic features. The CCFT module utilizes the self-attention mechanism to reintegrate semantic information from different stages into cross-level global features to reduce the semantic asymmetry between features at different levels. The CCFA module adaptively acquires the importance of each feature channel based on a global perspective in a network learning manner, enhancing effective information grasping and suppressing non-important features to mitigate semantic gaps. The combination of CCFT and CCFA can guide the effective fusion of different levels of features more powerfully with a global perspective. The consistent architecture of the encoder and decoder also alleviates the semantic gap. Experimental results suggest that the proposed CFATransUnet achieves state-of-the-art performance on four datasets. The code is available at https://github.com/CPU0808066/CFATransUnet.

Deep learning enables the discovery of a novel cuproptosis-inducing molecule for the inhibition of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common and deadly cancers in the world. The therapeutic outlook for HCC patients has significantly improved with the advent and development of systematic and targeted therapies such as sorafenib and lenvatinib; however, the rise of drug resistance and the high mortality rate necessitate the continuous discovery of effective targeting agents. To discover novel anti-HCC compounds, we first constructed a deep learning-based chemical representation model to screen more than 6 million compounds in the ZINC15 drug-like library. We successfully identified LGOd1 as a novel anticancer agent with a characteristic levoglucosenone (LGO) scaffold. The mechanistic studies revealed that LGOd1 treatment leads to HCC cell death by interfering with cellular copper homeostasis, which is similar to a recently reported copper-dependent cell death named cuproptosis. While the prototypical cuproptosis is brought on by copper ionophore-induced copper overload, mechanistic studies indicated that LGOd1 does not act as a copper ionophore, but most likely by interacting with the copper chaperone protein CCS, thus LGOd1 represents a potentially new class of compounds with unique cuproptosis-inducing property. In summary, our findings highlight the critical role of bioavailable copper in the regulation of cell death and represent a novel route of cuproptosis induction.