Machine-Learning-Assisted Rational Design of Si─Rhodamine as Cathepsin-pH-Activated Probe for Accurate Fluorescence Navigation.

High-performance fluorescent probes stand as indispensable tools in fluorescence-guided imaging, and are crucial for precise delineation of focal tissue while minimizing unnecessary removal of healthy tissue. Herein, machine-learning-assisted strategy to investigate the current available xanthene dyes is first proposed, and a quantitative prediction model to guide the rational synthesis of novel fluorescent molecules with the desired pH responsivity is constructed. Two novel Si─rhodamine derivatives are successfully achieved and the cathepsin/pH sequentially activated probe Si─rhodamine─cathepsin-pH (SiR─CTS-pH) is constructed. The results reveal that SiR─CTS-pH exhibits higher signal-to-noise ratio of fluorescence imaging, compared to single pH or cathepsin-activated probe. Moreover, SiR─CTS-pH shows strong differentiation abilities for tumor cells and tissues and accurately discriminates the complex hepatocellular carcinoma tissues from normal ones, indicating its significant application potential in clinical practice. Therefore, the continuous development of xanthene dyes and the rational design of superior fluorescent molecules through machine-learning-assisted model broaden the path and provide more advanced methods to researchers.

Ultrasound-assisted extraction of polyphenols from lotus rhizome epidermis by alcohol/salt-based aqueous two-phase system: Optimization, extraction mechanism and antioxidant activities.

In this study, ultrasonic-assisted (UA) alcohol/salt-based aqueous two-phase system (ATPS) method was constructed to extract lotus rhizome epidermis (LRE) polyphenols. The extraction conditions were optimized as salt concentration 26.75 %, ethanol concentration 25.45 %, ultrasonic power 487 W and liquid-solid ratio 35.33 mL/g by comparing response surface methodology (RSM) and artificial neural network (ANN) models. Then, l-dopa (2.35 ± 0.036 mg/g dw), gallocatechin (1.66 ± 0.0035 mg/g dw) and epigallocatechin (1.37 ± 0.0035 mg/g dw) were determined as major polyphenols in LRE by using UA-ATPS method. Moreover, study showed that ultrasound, van der Waals force, hydrogen bond and salting out could accelerate the mass transfer and extraction of polyphenols in LRE cells. The high-pressure cavity and collapse effect of ultrasound could also accelerate the extraction of polyphenols. In vitro antioxidant experiments showed that LRE polyphenols have good antioxidant ability. In sum, this study developed a green and efficient extraction method to enhance the profitability of LRE in food and medicine industries.

Construction of a novel aminofluorene-based ratiometric near-infrared fluorescence probe for detecting carboxylesterase activity in living cells.

Herein, we constructed a novel aminofluorene-based fluorescence probe (FEN-CE) for the detection of carboxylesterase (CE) in living cells by a ratiometric near-infrared (NIR) fluorescence signal. FEN-CE with NIR emission (650 nm) could be hydrolyzed specifically by CE and transformed to FENH with the release of the self-immolative group, which exhibited a red-shifted emission peak of 680 nm. In addition, FEN-CE showed high selectivity for CE and was successfully used in the detection of CE activity in living cells through its ratiometric NIR fluorescence signals.

Mechanism for gel formation of pectin from mealy and crisp lotus rhizome induced by Na+ and D-glucono-d-lactone.

Lotus rhizome residue, a cell wall material produced during the production of lotus rhizome starch, has long been underutilized. This study aims to extract pectin-rich polysaccharides from the cell wall of lotus rhizome and investigate their gelation mechanism in order to improve their industrial applicability. The results indicated that both CP and MP (pectin extracted from crisp and mealy lotus rhizome) exhibited a highly linear low methoxyl pectin structure, with the primary linkage mode being →4)-GalpA-(1→. The pectin chains in MP were found to be more flexible than those in CP. Then the impact of Na+, D-glucono-d-lactone (GDL), urea, sodium dodecyl sulfate (SDS), either individually or in combination, on the rheological characteristics of gels was evaluated. The results indicated that gels induced by GDL exhibited favorable thermoreversible properties, whereas the thermoreversibility of Na+-induced gels is poor. In addition to hydrogen bonding and ionic interactions, hydrophobic interactions also play a significant role in the formation of pectin gels. This study offers theoretical guidance and methodologies to improve the utilization rate of lotus rhizome starch processing by-products, while also provides novel insights into the correlation between LMP structure and gelation mechanism.

Bibliometric and visualized analysis of applying tumor markers in lung cancer diagnosis from 2000 to 2022.

Background: Lung cancer (LC) is the leading cause of cancer-related deaths worldwide. Tumor marker (TM) detection can indicate the existence and growth of a tumor and has therefore been used extensively for diagnosing LC. Here, we conducted a bibliometric analysis to examine TM-related publications for LC diagnosis to illustrate the current state and future trends of this field, as well as to identify additional promising TMs with high sensitivity. Methods: Publications regarding TMs in LC diagnosis were downloaded from the Web of Science Core Collection. CiteSpace was applied to perform a bibliometric analysis of journals, cocitation authors, keywords, and references related to this field. VOSviewer was used to generate concise diagrams about countries, institutions, authors, and keywords. Changes in the TM research frontier were analyzed through citation burst detection. Results: A total of 990 studies were analyzed in this work. The collaboration network analysis revealed that the People's Republic of China, Yonsei University, and Molina R were the most productive country, institution, and scholar, respectively. Additionally, Molina R was the author with the most citations. The National Natural Science Foundation of China was the largest funding source. "Carcinoembryonic antigen (CEA) as tumor marker in lung cancer" was the top reference with the most citations, Lung Cancer was the core journal, and "serum tumor marker" experienced a citation burst over the past 5 years. Conclusion: This bibliometric analysis of TMs in LC diagnosis presents the current trends and frontiers in this field. We summarized the research status of this field and the methods to improve the diagnostic efficacy of traditional serum TMs, as well as provided new directions and ideas for improving the LC clinical detection rate. Priority should be given to the transformation of computer-assisted diagnostic technology for clinical applications. In addition, circulating tumor cells, exosomes, and microRNAs were the current most cutting-edge TMs.

Molecular Engineering of Sulfone-Xanthone Chromophore for Enhanced Fluorescence Navigation.

Enriching the palette of high-performance fluorescent dyes is vital to support the frontier of biomedical imaging. Although various rhodamine skeletons remain the premier type of small-molecule fluorophores due to the apparent high brightness and flexible modifiability, they still suffer from the inherent defect of small Stokes shift due to the nonideal fluorescence imaging signal-to-background ratio. Especially, the rising class of fluorescent dyes, sulfone-substituted xanthone, exhibits great potential, but low chemical stability is also pointed out as the problem. Molecular engineering of sulfone-xanthone to obtain a large Stokes shift and high stability is highly desired, but it is still scarce. Herein, we present the combination modification method for optimizing the performance of sulfone-xanthone. These redesigned fluorescent skeletons owned greatly improved stability and Stokes shift compared with the parent sulfone-rhodamine. To the proof of bioimaging capacity, annexin protein-targeted peptide LS301 was introduced to the most promising dyes, J-S-ARh, to form the tumor-targeted fluorescent probe, J-S-LS301. The resulting probe, J-S-LS301, can be an outstanding fluorescence tool for the orthotopic transplantation tumor model of hepatocellular carcinoma imaging and on-site pathological analysis. In summary, the combination method could serve as a basis for rational optimization of sulfone-xanthone. Overall, the chemistry reported here broadens the scope of accessible sulfone-xanthone functionality and, in turn, enables to facilitate the translation of biomedical research toward the clinical domain.

Emergent superconductivity in topological-kagome-magnet/metal heterostructures.

Itinerant kagome lattice magnets exhibit many novel correlated and topological quantum electronic states with broken time-reversal symmetry. Superconductivity, however, has not been observed in this class of materials, presenting a roadblock in a promising path toward topological superconductivity. Here, we report that novel superconductivity can emerge at the interface of kagome Chern magnet TbMn6Sn6 and metal heterostructures when elemental metallic thin films are deposited on either the top (001) surface or the side surfaces. Superconductivity is also successfully induced and systematically studied by using various types of metallic tips on different TbMn6Sn6 surfaces in point-contact measurements. The anisotropy of the superconducting upper critical field suggests that the emergent superconductivity is quasi-two-dimensional. Remarkably, the interface superconductor couples to the magnetic order of the kagome metal and exhibits a hysteretic magnetoresistance in the superconducting states. Taking into account the spin-orbit coupling, the observed interface superconductivity can be a surprising and more realistic realization of the p-wave topological superconductors theoretically proposed for two-dimensional semiconductors proximity-coupled to s-wave superconductors and insulating ferromagnets. Our findings of robust superconductivity in topological-Chern-magnet/metal heterostructures offer a new direction for investigating spin-triplet pairing and topological superconductivity.

Potential significance of changes in serum levels of IL-17, TNF-α and DKK-1 in the progression of the rheumatoid arthritis.

To detect the value of serum interleukin-17 (IL-17), tumour necrosis factor-α (TNF-α), and Dickkopf-1 (DKK-1) in rheumatoid arthritis (RA) at different disease stages. 141 RA patients were randomly obtained and diagnosed in a large tertiary first-class hospital in Jiangxi Province from November 2021 to January 2022. RA was divided into 38 low activity and remission phase (low remission patients), 72 moderate activity patients, 41 high activity patients, according to the disease activity score 28 (DAS28) of RA and 70 healthy controls. IL-17 and TNF-α in serum detected by flow cytometry; DKK-1by ELISA; rheumatoid factor (RF) and C-reactive protein (CRP) by rate scattering turbidimetry; erythrocyte sedimentation rate (ESR) by Widmanstat method; anti-cyclic citrullinated polypeptide antibody (Anti-CCP) by chemiluminescence. The changes among the groups were statistically analysed and evaluated their diagnostic value. ①Anti-CCP, CRP, and ESR levels in the moderate-to-high activity group were higher than controls, while IL-17, TNF-α, and DKK-1levels higher than low remission group, moderate activity group and controls (p < 0.05). ②IL-17, TNF-α and DKK-1 were positively correlated with RA disease activity, with the correlations of IL-17, TNF-α and DKK-1 all over 0.5 (p < 0.05). ③The ROC curve showed that among all indices the AUC of DKK-1 was the largest, 0. 922, and has the highest sensitivity and negative predictive value for RA, 0.965 and 0.953, respectively. The specificity and positive predictive value of TNF-α is highest, 0.918 and 0.921, respectively, combined them had the highest predictive value in moderate-to-high activity RA, with AUC of 0.968, and had the highest sensitivity of 0.965. The IL-17, TNF-α and DKK-1 levels were elevated in RA and positively correlated with disease activity, involved in the Wnt signalling pathway of inflammatory and joint destructive effects, combining them to monitor the RA disease process and biologically treat the cytokines in the pathogenesis of RA were valuable.

Effect of waste tire rubber crumb on impermeability of cement-stabilized soil.

To alleviate the application limitations of cement-stabilized soil in impermeable engineering and promote the recycling of waste rubber tires, crumb rubber produced from waste rubber tires was used to improve the engineering properties of the soil. The effect of crumb rubber on the permeability of the soil under different conditions was investigated using compression, compaction, and permeability tests. Crumb rubber can effectively improve the impermeability of cement-stabilized soil. The impermeability efficiency of crumb rubber is between 11% and 45%. Cleaning crumb rubber with water and Na2CO3 solution can reduce the hydraulic conductivity of rubberized cement-stabilized soil (RCSS) by 7.9%-63.6%. This, in turn, increases the unconfined compressive strength by 4.1%-25.5%. The hydraulic conductivity of the RCSS decreases with an increase in the cement content, curing duration, and void ratio. A crumb rubber concentration of 10%-20% is suitable for enhancing the impermeability of the RCSS and satisfying its strength requirements. The NOF of the equation used to predict the hydraulic conductivity of the RCSS by the rubber content, cement content, and curing duration is less than 0.35. The linear correlation between the predicted and measured values of hydraulic conductivity was determined to be 0.995 from the k-quc correlation model. The results show that the hydraulic conductivity of RCSS can be estimated reliably based on the mix ratio and compressive strength.

Effect of pulp cell wall polysaccharides on citrus fruit with different mastication traits.

Mastication trait is a primary quality attribute of citrus fruit, influencing consumer demands and industrial processing conditions. However, the underlying causes of differences in mastication traits of citrus remain unclear. In this study, microscopy, spectroscopy and diffraction techniques were applied to investigate the physicochemical properties of Hongmeiren (HMR), Satsuma (WM) and Nanfeng tangerine (NF) with superior, moderate and inferior mastication traits, respectively. Ultrastructure indicated that NF had more neatly arranged and regularly shaped cells than HMR and WM. The monosaccharide composition of NF revealed that multi-branched Na2CO3-soluble pectin (NSF) enhanced intercellular adhesion. Additionally, FT-IR analysis revealed more intense vibrations of O2-H····O6 intramolecular hydrogen bonds within NF cellulose, which resulted in a higher crystallinity of cellulose (73.75%) than HMR (32.53%) and WM (43.76%). Overall, the high content and crystallinity of cellulose, the multi-branched NSF and the high content of hemicellulose contributed to the inferior mastication trait of citrus fruit.

Pair density wave state in a monolayer high-Tc iron-based superconductor.

The pair density wave (PDW) is an extraordinary superconducting state in which Cooper pairs carry non-zero momentum1,2. Evidence for the existence of intrinsic PDW order in high-temperature (high-Tc) cuprate superconductors3,4 and kagome superconductors5 has emerged recently. However, the PDW order in iron-based high-Tc superconductors has not been observed experimentally. Here, using scanning tunnelling microscopy and spectroscopy, we report the discovery of the PDW state in monolayer iron-based high-Tc Fe(Te,Se) films grown on SrTiO3(001) substrates. The PDW state with a period of λ ≈ 3.6aFe (aFe is the distance between neighbouring Fe atoms) is observed at the domain walls by the spatial electronic modulations of the local density of states, the superconducting gap and the π-phase shift boundaries of the PDW around the vortices of the intertwined charge density wave order. The discovery of the PDW state in the monolayer Fe(Te,Se) film provides a low-dimensional platform to study the interplay between the correlated electronic states and unconventional Cooper pairing in high-Tc superconductors.

Rational Design of pH-Independent and High-Fidelity Near-Infrared Tunable Fluorescent Probes for Tracking Leucine Aminopeptidase In Vivo.

Accurate detection of target analytes and generation of high-fidelity fluorescence signals are particularly critical in life sciences and clinical diagnostics. However, the majority of current NIR-I fluorescent probes are vulnerable to pH effects resulting in signal distortion. In this work, a series of fluorescence-tunable and pH-independent probes are reported by combining optically tunable groups of unsymmetric Si-rhodamines and introducing the methoxy instead of the spiro ring on the benzene ring at position 9. To validate the concept, the leucine aminopeptidase response site was introduced into Si-2,6OMe-NH2 with the best optical properties to synthesize Si-LAP for monitoring the intrahepatic LAP in vivo. Therefore, the design approach may provide a new and practical strategy for designing innovative functional fluorescent probes and generating high-stability and high-fidelity fluorescent signals.

Analysis of pectin-cellulose interaction in cell wall of lotus rhizome with assistance of ball-milling and galactosidase.

The current study sought to depict the structural feature of polysaccharides extracted from Na2CO3 unextractable fraction (LUN) of lotus rhizome using galactosidase with assistance of ball milling. The extracted polysaccharides were a complex of cellulose microfibrils and the RG-I structural domain of pectin, and the top three monosaccharides were glucose, galactose and galactose uronic acid, which allowed to tune the properties of the enzyme-hydrolyzed polysaccharide from LUN after 15 and 45 min of ball milling. The data of XRD revealed that pectin has a masking effect on the diffraction peaks of cellulose components. The removing of the polysaccharides could increase the degree of crystallinity and the pectin-cellulose interaction mainly occured through the galactan side chain was speculated. Textural characterization by SEM exhibited a cross-linked rod-like structure, which is similar to the structure of cellulose microfibrils. The morphological analysis of AFM revealed that L15-P (enzyme-hydrolyzed polysaccharide from LUN after 15 min of ball milling) contained relatively ordered and uniform network structures. Overall, the present study provides an important insight into cell wall of lotus rhizome matrix polysaccharide.

Migration from Lysosome to Nucleus: Monitoring Lysosomal Alkalization-Related Biological Processes with an Aminofluorene-Based Probe.

Aberrant lysosomal alkalization is associated with various biological processes, such as oxidative stress, cell apoptosis, ferroptosis, etc. Herein, we developed a novel aminofluorene-based fluorescence probe named FAN to monitor the lysosomal alkalization-related biological processes by its migration from lysosome to nucleus. FAN possessed NIR emission, large Stokes shift, high pH stability, and high photostability, making it suitable for real-time and long-term bioimaging. As a lysosomotropic molecule, FAN can accumulate in lysosomes first and then migrate to the nucleus by right of its binding capability to DNA after lysosomal alkalization. In this manner, FAN was successfully used to monitor these physiological processes which triggered lysosomal alkalization in living cells, including oxidative stress, cell apoptosis, and ferroptosis. More importantly, at higher concentrations, FAN could also serve as a stable nucleus dye for the fluorescence imaging of the nucleus in living cells and tissues. This novel multifunctional fluorescence probe shows great promise for application in lysosomal alkalization-related visual research and nucleus imaging.

Acetic Acid Immersion Alleviates the Softening of Cooked Sagittaria sagittifolia L. Slices by Affecting Cell Wall Polysaccharides.

This study investigated the mechanism for acetic acid pretreatment to improve cell wall integrity and thereby enhance the hardness of cooked Sagittaria sagittifolia L. slices by affecting polysaccharides in the cell wall. Distilled water immersion and 0.6% acetic acid immersion (the solid/liquid ratio is 1:10) for 15 h at room temperature could result in the conversion of pectin through different reactions during thermal processing. Combined in situ and in vitro analysis demonstrated that acetic acid pretreatment could promote the interaction of cellulose microfiber or hemicellulose with RG-Ⅰ side chains during thermal processing of S. sagittifolia L. slices, promote the entanglement between linear pectin molecules and make hemicellulose show a lower molecular weight under cooking, making it easy to firmly bind to pectin, which resulted in texture changes. The findings may help improve the texture of thermally processed vegetables and fruits and deep processing of starchy vegetables.

γ-Glutamyltranspeptidase and pH based "AND" logic gate fluorescent probe for orthotopic breast tumor imaging.

An "AND" logic gate-based NIR fluorescent probe Si-NH2-Glu was developed based on novel meso-amine Si-Rhodamine, which combined γ-glutamyl transpeptidase and pH dual-responsive sites. The features of Si-NH2-Glu enable it to be applied in orthotopic tumor imaging and fluorescence-guided surgery.

Rational Design of Polymethine Dyes with NIR-II Emission and High Photothermal Conversion Efficiency for Multimodal-Imaging-Guided Photo-Immunotherapy.

Phototheranostics have emerged and flourished as a promising pattern for cancer theranostics owing to their precise photoinduced diagnosis and therapeutic to meet the demands of precision medicine. The diagnosis information and therapeutic effect are directly determined by the fluorescence imaging ability and photothermal conversion efficiency (PCE) of phototheranostic agents. Hence, how to balance the competitive radiative and nonradiative processes of phototheranostic agents is the key factor to evaluate the phototheranostic effect. Herein, molecules named ICRs with high photostaibility  are rationally designed, exhibiting fluorescence emission in the second near-infrared window (NIR-II, 1000-1700 nm) and high PCE, which are related to the strong donor-acceptor (D-A) interaction and high reorganization energy Noteworthily, ICR-Qu with stronger D-A interaction and a large-sized conjugated unit encapsulated in nanoparticles exhibits high PCE (81.1%). In addition, ICR-QuNPs are used for fluorescence imaging (FLI), photoacoustic imaging (PAI), and photothermal imaging (PTI) to guide deep-tissue photonic hyperthermia, achieving precise removal and inhibition of breast cancer. Furthermore, combined with α-PD-1, ICR-QuNPs show huge potential to be a facile and efficient tool for photo-immunotherapy. More importantly, this study not only reports an "all-in-one" polymethine-based phototheranostic agent, but also sheds light on the exploration of versatile organic molecules for future practical applications.

Discrete scale invariance of the quasi-bound states at atomic vacancies in a topological material.

Recently, log-periodic quantum oscillations have been detected in the topological materials zirconium pentatelluride (ZrTe5) and hafnium pentatelluride (HfTe5), displaying an intriguing discrete scale invariance (DSI) characteristic. In condensed materials, the DSI is considered to be related to the quasi-bound states formed by massless Dirac fermions with strong Coulomb attraction, offering a feasible platform to study the long-pursued atomic-collapse phenomenon. Here, we demonstrate that a variety of atomic vacancies in the topological material HfTe5 can host the geometric quasi-bound states with a DSI feature, resembling an artificial supercritical atom collapse. The density of states of these quasi-bound states is enhanced, and the quasi-bound states are spatially distributed in the "orbitals" surrounding the vacancy sites, which are detected and visualized by low-temperature scanning tunneling microscope/spectroscopy. By applying the perpendicular magnetic fields, the quasi-bound states at lower energies become wider and eventually invisible; meanwhile, the energies of quasi-bound states move gradually toward the Fermi energy (EF). These features are consistent with the theoretical prediction of a magnetic field-induced transition from supercritical to subcritical states. The direct observation of geometric quasi-bound states sheds light on the deep understanding of the DSI in quantum materials.

Tumor necrosis factor-alpha stimulated gene-6: A biomarker reflecting disease activity in rheumatoid arthritis.

BACKGROUND: To explore the serum tumor necrosis factor-alpha stimulated gene-6 (TSG-6) level and its association with disease activity in rheumatoid arthritis (RA) patients. METHODS: We recruited 176 RA patients, 178 non-RA patients (lupus erythematosus, osteoarthritis, ulcerative colitis, ankylosing spondylitis and psoriasis) and 71 healthy subjects. Serum TSG-6 levels were detected by enzyme-linked immunosorbent assay (ELISA). RA patients were divided into inactive RA and active RA groups by disease activity score of 28 joints based on C-reactive protein (DAS28-CRP). The receiver operating characteristic (ROC) curve and Spearman's rank correlation test analyzed the correlation between TSG-6 concentration and RA disease activity. RESULTS: Tumor necrosis factor-alpha stimulated gene-6 levels in the RA group were increased (p < 0.01). TSG-6 concentrations indicated an upward tendency with increased disease activity; The area under the curve (AUC) of TSG-6 for diagnosing RA and assessing the severity of RA were 0.78 and 0.80, respectively; The combination of TSG-6 and anti-mutated citrullinated vimentin antibodies (anti-MCV) (sensitivity:98.4%)improved the diagnostic accuracy of RA. Binary logistic regression analysis showed that TSG-6 was an independent risk factor related to the severity of RA, and OR (95% CI) was 1.2 (1.003-1.453). CONCLUSION: The TSG-6 levels in RA patients were elevated and related to disease activity. Therefore, TSG-6 may serve as a new potential biomarker for evaluating RA disease activity.

Sodium bicarbonate reduces the cooked hardness of lotus rhizome via side chain rearrangement and pectin degradation.

In this study, 0.1% (W/V) sodium bicarbonate (SB) solution was used to soften lotus rhizome, and the mechanism was characterized by monoclonal antibodies labeling (mAbs) and atomic force microscopy (AFM). The results showed that the cell wall of lotus rhizome was disintegrated under SB treatment. In addition, the mAbs results revealed that low-esterified homogalacturonan (HG) at the tricellular junction was degraded, the rearrangement of Ara and the interaction between Gal and cellulose may be related to the texture changes. Compared with distilled water treatment, SB treatment reduced the relative content of pectin from 34.1% to 19.1% while increased that of cellulose from 65.9% to 80.9%. AFM results revealed that the height of CSF skeleton decreased from about 32 nm to 1.5 nm. These results clearly demonstrate that cooking with 0.1% SB can soften lotus rhizome through degradation of pectin and arrangement of side chains of rhamnogalacturonan-Ⅰ (RG-Ⅰ).