KinomeMETA: a web platform for kinome-wide polypharmacology profiling with meta-learning.

Kinase-targeted inhibitors hold promise for new therapeutic options, with multi-target inhibitors offering the potential for broader efficacy while minimizing polypharmacology risks. However, comprehensive experimental profiling of kinome-wide activity is expensive, and existing computational approaches often lack scalability or accuracy for understudied kinases. We introduce KinomeMETA, an artificial intelligence (AI)-powered web platform that significantly expands the predictive range with scalability for predicting the polypharmacological effects of small molecules across the kinome. By leveraging a novel meta-learning algorithm, KinomeMETA efficiently utilizes sparse activity data, enabling rapid generalization to new kinase tasks even with limited information. This significantly expands the repertoire of accurately predictable kinases to 661 wild-type and clinically-relevant mutant kinases, far exceeding existing methods. Additionally, KinomeMETA empowers users to customize models with their proprietary data for specific research needs. Case studies demonstrate its ability to discover new active compounds by quickly adapting to small dataset. Overall, KinomeMETA offers enhanced kinome virtual profiling capabilities and is positioned as a powerful tool for developing new kinase inhibitors and advancing kinase research. The KinomeMETA server is freely accessible without registration at https://kinomemeta.alphama.com.cn/.

Construction of Ru Single-Atoms on Ceria to Reform the Products of CO2 Photoreduction.

Highly selective production of CH4 from photocatalytic CO2 reduction is still a great challenge which involves the kinetically unfavorable transfers of 8 protons and 8 electrons. Herein, CeO2 photocatalysts incorporated with isolated Ru single-atoms have been fabricated, which demonstrate dramatically elevated selectivity of CH4 from CO2 reduction. The introduced Ru single-atoms promote carrier separation and accelerate electron transfer, which efficiently enhances the photocatalytic activity. Density functional theory (DFT) calculations and in situ FT-IR analysis manifest that the Ru single-atom active sites play an indispensable role in strengthening the adsorption of *CO intermediate on the catalyst surface and promoting H2O oxidation to generate abundant protons, thus favoring *CO protonation into *CHxO (x = 1, 2, 3) species and final deoxygenation into CH4. This work provides an effective strategy by constructing single-atom active sites to modulate and stabilize the key intermediates of CO2 photoreduction to improve the selectivity of the target products.

B-cell specific Moloney murine leukemia virus insertion site 1 contributes to invasion, metastasis, and poor prognosis in salivary adenoid cystic carcinoma.

Background/purpose: Upregulation of B-cell specific Moloney murine leukemia virus insertion site 1 (BMI-1) has been involved in the invasion, metastasis, and poor prognosis of many cancers. The aim of this study was to evaluate the levels and clinical significance of BMI-1 in saliva of patients with salivary adenoid cystic carcinoma (SACC), and to analyze biological function and mechanism of BMI-1 in the invasion and metastasis of SACC. Materials and methods: The levels of BMI-1 in saliva and tumor tissues of SACC patients were determined. The correlation of salivary BMI-1 levels with clinicopathological parameters and clinical outcomes in patients with SACC was analyzed. Additionally, the effects of BMI-1 on wound-healing, transwell invasion, and epithelial-mesenchymal transition (EMT)-related protein expression in vitro as well as on tumorigenicity and experimental lung metastasis in vivo were investigated through exogenous overexpression and silencing of BMI-1 in SACC cells. Results: BMI-1 levels increased in saliva and tumor tissues in SACC patients with invasion or metastasis. High salivary BMI-1 levels were correlated with poor TNM stage, poor overall survival, and disease-free survival. Exogenous expression of BMI-1 in SACC-83 promoted its migration and invasion, while silencing BMI-1 in SACC-LM inhibited its migration and invasion in vitro and suppressed tumorigenesis and lung metastasis in vivo. Furthermore, BMI-1 regulated the expression of EMT-related proteins in SACC. Conclusion: Our study shows that BMI-1 can serve as a valuable biomarker to identify tumor invasion and metastasis in SACC, predict its prognosis, and act as a promising therapeutic target for SACC.

New strategy for reinforcing polylactic acid composites: Towards the insight into the effect of biochar microspheres.

Having even particle size and regular morphology of biochar microspheres (BM) provides the possibility for preparing polylactic acid (PLA) films. Hence, the novelty is proposing a strategy for reinforcing PLA by BM. It was found that BM exhibited regular morphology, higher thermal stability, even particle size, and better pore characteristics. Although adding BM decreased the toughness of PLA due to the poor compatibility between BM and PLA, the nucleation effect of BM facilitated the crystallization in the PLA system. The tensile strength and modulus of BM/PLA composite films increased first and then decreased with increasing BM content. The stress concentration formed by BM particle agglomeration was responsible for the tensile strength and modulus decreases of BM/PLA composite films under higher BM addition. 2% BM added and 3% added composite films exhibited the best tensile strength and modulus with 64.99 MPa and 1.59 GPa, which was mainly attributed to the proper proportion of BM to PLA and the uniform distribution of BM in PLA. The results of this study confirmed the positive reinforcing effect of BM in PLA and are expected to be available in the composite film field.

Recyclable detection of gefitinib in clinical sample mediated by multifunctional Ag-anchored g-C3N4/MoS2 composite substrate.

Surface-enhanced Raman scattering (SERS) technology enables to satisfy the increasing demand of clinical drug monitoring due to the superiority of fingerprint recognition, real-time response, and nondestructive collection. Here, a novel graphitic carbon nitride (g-C3N4)/ molybdenum disulfide (MoS2)/Ag composite substrate with a 3D surface structure was successfully developed for the recyclable detection of gefitinib in serum. Attributed to the uniform and dense "hotspots" on the shrubby active surfaces in conjunction with the potential synergistic chemical enhancement of g-C3N4/MoS2 heterosystem, a remarkable SERS sensitivity with an attractive enhancement factor value of 3.3 × 107 was demonstrated. Meanwhile, a type-II heterojunction between g-C3N4 and MoS2 enabled more efficient diffusion of photogenerated e--h+ pairs assisted by the localized surface plasmon resonance of Ag NPs, which contributed to the reliable recyclable detection of gefitinib. The ultra-low limit of detection at 10-5 mg/mL and high recycling rates of gefitinib beyond 90% in serum were successfully realized. The results demonstrated the as-prepared SERS substrate has tremendous potential to be untilized for in-situ drug diagnostics.

First Report of Fusarium denticulatum Causing Chlorotic Leaf Distortion of Sweetpotato in China.

Sweetpotato (Ipomoea batatas) is one of the most important crops in China. To gain a clearer picture of the occurrence of diseases on sweetpotato, 50 fields (100 plants/field) were randomly surveyed in prominent sweetpotato growing areas of Lulong county, Hebei Province in the years 2021-2022. Plants showing chlorotic leaf distortion with mildly twisted young leaves and stunted vines were observed frequently. It was similar to the symptoms of chlorotic leaf distortion of sweetpotato (Clark et al. 2013). The incidence of disease with patch pattern ranged from 15% to 30%. Ten symptomatic leaves were excised, surface disinfested with 2% sodium hypochlorite for 1 min, rinsed three times in sterilized ddH2O, and cultured on potato dextrose agar (PDA) at 25°C. Nine fungal isolates were obtained. A pure culture of representative isolate FD10 obtained after serial hyphal tip transfer was examined for morphological and genetic characters. Colonies of isolate FD10 on PDA at 25°C were slow growing (4±0.1mm/day) with aerial, white-to-pink mycelium. Lobed colonies had greyish-orange pigmentation in reverse and conidia aggegated in false heads. Conidiophores were prostrate and short. Phialides were mostly monophialidic but occasionally polyphialidic. Polyphialidic openings often denticulate in a rectangular arrangement. Microconidia were abundant, long, oval to allantoid, mostly none or one septate, and 4.79 to 9.53 × 2.08 to 3.22 µm (n = 20). Macroconidia were fusiform to falcate with a beaked apical cell and a footlike basal cell, 3 to 5 septate, and 25.03 to 52.92 × 2.56 to 4.49 µm. Chlamydospores were absent. All in agreement with the morphology of Fusarium denticulatum (Nirenberg and O'Donnell 1998). Genomic DNA of isolate FD10 was extracted. The EF-1α and ß-tubulin genes were amplified and sequenced (O'Donnell and Cigelnik 1997; O'Donnell et al. 1998). The obtained sequences were deposited in GenBank (accession nos. OQ555191 and OQ555192). BLASTn revealed that those sequences showed 99.86% (EF-1α) and 99.93% (ß-tubulin) homology with the relative sequences of F. denticulatum type strain CBS407.97 (accession nos. MT011002.1 and MT011060.1), respectively. Furthermore, a neighbor-joining phylogenetic tree based on the EF-1α and ß-tubulin sequences revealed that the isolate FD10 clustered with F. denticulatum. Based on morphological characteristics and sequence analysis, the isolate FD10 associated with chlorotic leaf distortion of sweetpotato was identified as F. denticulatum. Pathogenicity tests were performed by immersing ten 25-cm-long vine-tip cuttings of cultivar Jifen 1 origin from tissue culture in a conidial suspension (1 × 106 conidia per ml) of isolate FD10. Vines immersed in sterile distilled water used as a control. All inoculated plants in 25-cm plastic pots were incubated in a climate chamber at 28℃ and 80% RH for two and half months and the control were incubated in a separate climate chamber. Nine inoculated plants developed chlorotic terminals, moderate interveinal chlorosis and slight leaf distortion. No symptoms were observed on the control plants. The pathogen was reisolated from inoculated leaves and matched the morphological and molecular characteristics of the original isolates, thus fulfilling Koch's postulates. To our knowledge, this is the first report of F. denticulatum causing chlorotic leaf distortion of sweetpotato in China. Its identification will promote the management of this disease in China.

Monoterpene alcohols induced by sweet potato weevil larvae deter conspecific adults from feeding and oviposition.

BACKGROUND: Intraspecific competition is shared in the insect world, especially under the condition of limited food and space resources. To avoid intraspecific competition and increase offspring survival, insects have evolved various effective strategies. A widely-accepted tactic is employing chemical cues, which are frequently utilized as indicators of conspecific colonization. The sweet potato weevil (SPW), Cylas formicarius, is a destructive pest of sweet potatoes. Its larvae bore into sweet potatoes and alter the emission of odors. The present study aimed to investigate whether volatiles associated with SPW larvae feeding influence the behavioral preference of conspecific adults. RESULTS: Volatiles from SPW larvae-infested sweet potatoes were collected by a head-space method and analyzed using gas chromatography-electroantennogram detector (GC-EAD) and gas chromatography-mass spectrometry (GC-MS). Five compounds eliciting EAD responses from the antennae of both male and female adult SPW were identified from sweet potatoes with the third-instar larvae, including linalool, citronellol, nerol, geraniol, and ipomeamarone. Four monoterpene alcohols significantly repelled SPW adults from feeding and oviposition at higher doses in the behavioral preference bioassays. Among them, geraniol displayed the strongest repellent activities for SPW feeding and oviposition. These results suggested that SPW larvae could reduce colonization of adult SPWs by inducing monoterpene alcohols, thereby avoiding intraspecific competition. CONCLUSION: The present study demonstrated that volatile monoterpene alcohols induced by SPW larvae are chemical cues of larvae occupation for SPW adults to change their behavioral preference. Unveiling factors that mediate avoidance of intraspecific competition could help develop repellents or oviposition deterrents for SPW control. © 2023 Society of Chemical Industry.

SERS-based recyclable immunoassay mediated by 1T-2H mixed-phase magnetic molybdenum disulfide probe and 2D graphitic carbon nitride substrate.

Recently, non-metallic SERS-based immunoassay has attracted much attention due to its attractive chemical enhancement (CM), chemical stability, and biocompatibility. Herein, metallic (1T)-semiconductor (2H) mixed-phase magnetic molybdenum disulfide (MoS2) was rationally developed and combined with two-dimensional (2D) graphitic carbon nitride (g-C3N4) nanosheets to realize a SERS-based recyclable immunoassay of CA125. The Fe3O4 core promoted the reliable stacking of MoS2 nanoflakes into a flower-like shape with fully-exposed active surface. Particularly, the existence of 1T phase facilitated a noble-metal-comparable SERS activity due to the high electron density-induced charge transfer process with elevated efficiency. Moreover, a conversion from bulk to 2D nanosheet was swimmingly achieved for g-C3N4 via acid etching, whose large surface area full of active electrons and functional groups triggered an enhancement factor (EF) of 7.8 × 106. Based on a typical sandwich immunostructure, a limit of detection (LOD) as 4.96 × 10-4 IU/mL was demonstrated for CA125 in a recyclable process. Finally, such an immunosensor was employed to analyze clinical samples, indicating its prodigious potentiality in the early recognition and monitoring of cancer.

CoW Bimetallic Carbide Nanocatalysts: Computational Exploration, Confined Disassembly-Assembly Synthesis and Alkaline/Seawater Hydrogen Evolution.

Earth-abundant tungsten carbide exhibits potential hydrogen evolution reaction (HER) catalytic activity owing to its Pt-like d-band electronic structure, which, unfortunately, suffers from the relatively strong tungsten-hydrogen binding, deteriorating its HER performance. Herein, a catalyst design concept of incorporating late transition metal into early transition metal carbide is proposed for regulating the metal-H bonding strength and largely enhancing the HER performance, which is employed to synthesize CoW bi-metallic carbide Co6 W6 C by a "disassembly-assembly" approach in a confined environment. Such synthesized Co6 W6 C nanocatalyst features the optimal Gibbs free energy of *H intermediate and dissociation barrier energy of H2 O molecules as well by taking advantage of the electron complementary effect between Co and W species, which endows the electrocatalyst with excellent HER performance in both alkaline and seawater/alkaline electrolytes featuring especially low overpotentials, elevated current densities, and much-enhanced operation durability in comparison to commercial Pt/C catalyst. Moreover, a proof-of-concept Mg/seawater battery equipped with Co6 W6 C-2-600 as cathode offers a peak power density of 9.1 mW cm-2 and an open-circuit voltage of ≈1.71 V, concurrently realizing hydrogen production and electricity output.

A distinctive semiconductor-metalloid heterojunction: unique electronic structure and enhanced CO2 photoreduction activity.

Increasing the concentration and separation ability of charge carriers in photocatalysts has still been a crucial issue and challenge to achieve high CO2 photoreduction performance. Here, we construct a distinctive heterojunction between semiconductor (CeO2) and metalloid (CuS). It has been discovered that, different from conventional semiconductor and Schottky heterojunctions, in this system, electrons (esc-) located at the conduction band (CB) of CeO2 will transfer to the Fermi level in partially occupied band (CB) of CuS and accumulate there. Then, together with transition electrons (etr-) excited from the CB below Fermi level or fully filled band (B-1) of CuS, these esc- will further transfer to the lowest unoccupied band (B1) of CuS, finally participate in CO2 reduction reaction. Because the concentration and separation efficiency of charge carriers has been obviously increased, this heterojunction exhibits remarkably enhanced CO2 photoreduction performance. In-situ FTIR was conducted to explore the reaction process and the changes of intermediates on the surface of this catalyst during CO2 photoreduction. Given that this type of heterojunction can only be established between a semiconductor and a metalloid and exhibits special electron transfer behavior, this work really provides an unconventional strategy for the design of photocatalysts with superior CO2 photoreduction activity.

A real-time recombinase polymerase amplification assay for fast and accurate detection of Ditylenchus destructor.

Ditylenchus destructor is a plant-parasitic nematode that seriously infests sweet potato crop in China. Thus, fast and accurate detection of D. destructor in soil and plant tissue samples is of great significance. In this study, a real-time recombinase polymerase amplification (RPA) assay was developed for the rapid and accurate detection of D. destructor in various samples. The RPA assay could be easily operated and detected as low as 1/500 individual J4 nematode DNA per reaction in 20 min at 39 °C with high specificity. The assay meets the requirements of rapid detection prior to port quarantine as well as on-site real-time detection and can be applied to detect the parasite in soil and plant samples. The modified gDNA extraction method for a single nematode established in this study significantly reduced the time of detection and improved the applicability of the real-time RPA assay for on-site detection in different environments. The real-time RPA assay to detect D. destructor will be useful for epidemiological investigations in the field as well as for quarantine processes in the sweet potato and potato trade.

Bi-Sn Oxides for Highly Selective CO2 Electroreduction to Formate in a Wide Potential Window.

The electroreduction of CO2 into the highly value-added fuel formic acid (HCOOH) has been considered an ideal approach to convert renewable energy and mitigate environmental crisis. SnO2 electrode is one of the promising candidates to electrocatalytically convert CO2 to HCOOH, but its poor stability limits its future development and application. In this study, highly stable SnO2 /Bi2 O3 oxide catalysts are obtained by distributing SnO2 nanoparticles on the surface of Bi2 O3 sheets. The XPS spectra revealed an interfacial electronic transportation from Bi2 O3 sheets to SnO2 nanoparticles, which made SnO2 rich of electrons. The strong interfacial interaction protected the active sites of SnO2 from self-reduction in CO2 electroreduction reaction (CO2 RR), stabilizing SnO2 species in the composite catalyst even after long-term usage. Calculations based on density functional theory signified that the presence of Bi2 O3 favored the adsorption of HCOO* intermediate, improved the CO2 conversion into HCOOH on SnO2 /Bi2 O3 interface. As a result, the SnO2 /Bi2 O3 catalyst attained high performance on CO2 RR (the highest FE C 1 value of 90 % at -1.0 V vs. RHE), suppressing H2 evolution reaction (HER) at high potentials. In particular, the selectivity of HCOOH remained above 76 % in a wide potential window (from -1.0 to -1.4 V vs. RHE) and a long duration (12 h).

Chronic Neuroinflammation Induced by Lipopolysaccharide Injection into the Third Ventricle Induces Behavioral Changes.

The existence of Gram-negative bacteria in the brain, regardless of underlying immune status has been demonstrated by recent studies. The colocalization of lipopolysaccharide (LPS) with Aß1-40/42 in amyloid plaques supports the hypothesis that brain microbes may be the cause, triggering chronic neuroinflammation, leading to Alzheimer's disease (AD). To investigate the behavioral changes induced by infectious neuroinflammation, we chose the third ventricle as the site of a single LPS injection (20 µg or 80 µg) in male Wistar rats to avoid mechanical injury to forebrain structures while inducing widespread inflammation throughout the brain. Chronic neuroinflammation induced by LPS resulted in depressive-like behaviors and the impairment of spatial learning; however, there was no evidence of the development of pathological hallmarks (e.g., the phosphorylation of tau) for 10 months following LPS injection. The acceleration of cholesterol metabolism via CYP46A1 and the retardation of cholesterol synthesis via HMGCR were observed in the hippocampus of rats treated with either low-dose or high-dose LPS. The rate-limiting enzymes of cholesterol metabolism (CYP46A1) in SH-SY5Y cells and synthesis (HMGCR) in U251 cells were altered by inflammation stimulators, including LPS, IL-1ß, and TNF-α, through the TLR4/MyD88/NF-κB signaling pathway. The data suggest that chronic neuroinflammation provoked by the administration of LPS into the third ventricle may induce depressive-like symptoms and that the loss of cholesterol might be a biomarker of chronic neuroinflammation. The lack of pathological hallmarks of AD in our model indicates that Gram-negative bacteria infection might not be a single cause of AD.

The Inhibition of miR-873 Provides Therapeutic Benefit in a Lipopolysaccharide-Induced Neuroinflammatory Model of Parkinson's Disease.

Background and Purpose. Alterations in cholesterol homeostasis have been reported in cell and animal models of Parkinson's disease (PD), although there are inconsistent data about the association between serum cholesterol levels and risk of PD. Here, we investigated the effects of miR-873 on lysosomal cholesterol homeostasis and progressive dopaminergic neuron damage in a lipopolysaccharide-(LPS) induced model of PD. Experimental Approach. To evaluate the therapeutic benefit of the miR-873 sponge, rats were injected with a LV-miR-873 sponge or the control vector 3 days before the right-unilateral injection of LPS into the substantia nigra (SN) pars compacta, or 8 and 16 days after LPS injection. Normal SH-SY5Y cells or SH-SY5Y cells overexpressing α-synuclein were used to evaluate the distribution of α-synuclein and cholesterol in lysosomes and to assess the autophagic flux after miR-873 transfection or ABCA1 silencing. The inhibition of miR-873 significantly ameliorated the LPS-induced accumulation of α-synuclein and loss of dopaminergic neurons in the SN at the early stage. miR-873 mediated the inhibition of ABCA1 by LPS. miR-873 transfection or ABCA1 silencing increased the lysosomal cholesterol and α-synuclein levels, and decreased the autophagic flux. The knockdown of ABCA1 or A20, which are the downstream target genes of miR-873, exacerbated the damage to LPS-induced dopaminergic neurons. Conclusion and Implications. The results suggest that the inhibition of miR-873 may play a dual protective role by improving intracellular cholesterol homeostasis and neuroinflammation in PD. The therapeutic effects of the miR-873 sponge in PD may be due to the upregulation of ABCA1 and A20.

Transcriptome analyses of Ditylenchus destructor in responses to cold and desiccation stress.

The objective of this study was to identify molecular responses in Ditylenchus destructor to cold and desiccation by means of transcriptomes analyses. A total of 102,517 unigenes were obtained, with an average length of 1,076 bp, in which 58,453 (57%) had a functional annotation. A total of 1154 simple sequence repeats (SSRs) distributed over 1078 unigenes were detected. Gene expression profiles in response to cold and desiccation stress and the expression of specific stress-related genes were compared. Gene ontology analysis and pathway-based analysis were used to further investigate the functions of the differentially expressed genes. The reliability of the sequencing data was verified through quantitative real-time PCR analysis of 19 stress-related genes. RNA interference used to further assess the functions of the cold-related unigenes 15628 and 15596 showed that the knockdown of each of these genes led to decreased cold tolerance of D. destructor. Hence, this study revealed molecular processes and pathways active in cold- or dessication-treated nematodes. The transcriptome profiles presented in this study provide insight into the transcriptome complexity and will contribute to further understand stress tolerance in D. destructor.

Electron Configuration Modulation of Nickel Single Atoms for Elevated Photocatalytic Hydrogen Evolution.

The emerging metal single-atom catalyst has aroused extensive attention in multiple fields, such as clean energy, environmental protection, and biomedicine. Unfortunately, though it has been shown to be highly active, the origins of the activity of the single-atom sites remain unrevealed to date owing to the lack of deep insight on electronic level. Now, partially oxidized Ni single-atom sites were constructed in polymeric carbon nitride (CN), which elevates the photocatalytic performance by over 30-fold. The 3d orbital of the partially oxidized Ni single-atom sites is filled with unpaired d-electrons, which are ready to be excited under irradiation. Such an electron configuration results in elevated light response, conductivity, charge separation, and mobility of the photocatalyst concurrently, thus largely augmenting the photocatalytic performance.

Bisimidazole-based phosphorescent thiocyanatocadmates.

Simple room-temperature self-assemblies between Cd2+ salts, SCN- and bisimidazole molecules at pH = 2 created three new organically templated thiocyanatocadmates [H2(L1)][Cd(SCN)4]·H2O (L1 = 1,4-bis(1H-imidazol-1-yl)benzene) 1, [H2(L2)][Cd(SCN)4] (L2 = 1,3-bis(2-methylimidazol-1-yl)propane) 2, and [H2(L3)][Cd2(SCN)6] (L3 = 1,4-bis(2-methyl-1H-imidazol-1-yl)butane) 3. X-ray single-crystal diffraction analysis reveals that (i) in 1-3, the SCN- groups doubly bridge the Cd2+ centers to form different thiocyanatocadmates: a linear chain in 1; a zigzag chain in 2; and a 2-D layer network (63 net) in 3; and (ii) in 1, via Nbase-HNSCN interactions, the L1 molecules extend the thiocyanatocadmate chains into a 2-D supramolecular layer, whereas in 2, the zigzag thiocyanatocadmate chains self-assemble into a 3-D supramolecular network via weak SS interactions. Photoluminescence analysis indicates that the three title compounds all emit light: blue light for 1 and 2 and green light for 3. At low temperatures, the emission positions of the three compounds hardly change, but the emission intensities are largely enhanced. Interestingly, after turning off the UV lamp, 1 and 2 still briefly emit light (ca. 2 s), which means that 1 and 2 possess phosphorescence properties. Phosphorescence lifetimes at 77 K are 1619 ms for 1 and 247 ms for 2.

Nanocatalysts-Augmented and Photothermal-Enhanced Tumor-Specific Sequential Nanocatalytic Therapy in Both NIR-I and NIR-II Biowindows.

The tumor microenvironment (TME) has been increasingly recognized as a crucial contributor to tumorigenesis. Based on the unique TME for achieving tumor-specific therapy, here a novel concept of photothermal-enhanced sequential nanocatalytic therapy in both NIR-I and NIR-II biowindows is proposed, which innovatively changes the condition of nanocatalytic Fenton reaction for production of highly efficient hydroxyl radicals (•OH) and consequently suppressing the tumor growth. Evidence suggests that glucose plays a vital role in powering cancer progression. Encouraged by the oxidation of glucose to gluconic acid and H2 O2 by glucose oxidase (GOD), an Fe3 O4 /GOD-functionalized polypyrrole (PPy)-based composite nanocatalyst is constructed to achieve diagnostic imaging-guided, photothermal-enhanced, and TME-specific sequential nanocatalytic tumor therapy. The consumption of intratumoral glucose by GOD leads to the in situ elevation of the H2 O2 level, and the integrated Fe3 O4 component then catalyzes H2 O2 into highly toxic •OH to efficiently induce cancer-cell death. Importantly, the high photothermal-conversion efficiency (66.4% in NIR-II biowindow) of the PPy component elevates the local tumor temperature in both NIR-I and NIR-II biowindows to substaintially accelerate and improve the nanocatalytic disproportionation degree of H2 O2 for enhancing the nanocatalytic-therapeutic efficacy, which successfully achieves a remarkable synergistic anticancer outcome with minimal side effects.

Copper(i)-polymers and their photoluminescence thermochromism properties.

Under hydro(solvo)thermal conditions, four organic bidentate bridging N,N'-donor ligands 1,3-bis(2-methylimidazol-1-yl)propane (L1), 4,4'-di(1H-imidazol-1-yl)-1,1'-biphenyl (L2), 1,2-bis(2-methyl-1H-imidazol-1-ylmethyl)benzene (L3) and 5,6,7,8-tetrahydroquinoxaline (L4) were employed to react with CuBr/CuI, generating four 2-D layered copper(i)-polymer coordination polymer materials [Cu2Br2(L1)] 1, [CuI(L2)] 2, [CuI(L3)] 3 and [CuI(L4)0.5] 4. In 1-4, different Cu-X motifs are found: a cubic Cu4Br4 core in 1; a castellated Cu-I single chain in 2; a rhombic Cu2I2 core in 3; and a staircase-like Cu-I double chain in 4. The 2-D layer networks of 1-3 can all be simplified into a simple 44 topology (planar for 1 and 3; wave-like for 2), while the 2-D layer network of 4 has a 63 topology. The photoluminescence behaviors of 1-4 under a UV lamp suggest that 1 and 2 possess fluorescence thermochromism properties. Under the UV lamp, with the decrease in temperature, (i) 1 exhibits a yellow-to-red emission; (ii) 2 exhibits a yellow-to-green emission; (iii) 3 always emits green light; and (iv) 4 never emits light. These are further confirmed by their emission spectra. From 297 K to 77 K, the emission of 1 exhibits a large red shift from 561 nm to 623 nm; the emission of 2 exhibits a large blue shift from 571 nm to 515 nm; only a minor red shift is observed for the emission of 3; and no peaks appear in the emission spectra of 4. The crystal data of 1 and 2 at different temperatures have been collected for revealing the origination of their fluorescence thermochromism properties. Based on the above investigations, the effect of the rigidity/flexibility of the organic ligand on the fluorescence thermochromism properties of copper(i)-polymer coordination polymer materials is discussed. The quantum yields at 297 K and the photoluminescence lifetimes at 297 K and 77 K for 1-3 were also measured for better understanding their photoluminescence properties.

Transglutaminase 3 contributes to malignant transformation of oral leukoplakia to cancer.

Oral leukoplakia (OL) is the most common premalignancy in the oral cavity. The objective of this study was to investigate the biological role of transglutaminase 3 (TGM3) in malignant transformation of OL and its clinical value for predicting oral squamous cell carcinoma (OSCC) risk in patients with OL. Immunohistochemistry was used to measure TGM3 expression in OL samples from 98 patients. Patient clinicopathological and follow-up data were analyzed. The TGM3 biological role in OL cells was investigated in gain-of-function and loss-of-function assays, and the TGM3 downregulated mechanism in OLs was characterized. TGM3 mRNA and protein expressions were frequently downregulated in OL cells and samples. DNA hypermethylation was a mechanism of TGM3 downregulation. TGM3 overexpression and silencing affected the proliferation, colony formation, and apoptosis of OL cells through apoptosis-related protein dysregulations. Lower TGM3 levels were strongly associated with the grade of epithelial dysplasia and OSCC development. Multivariate analyses showed that TGM3 was the independent predictor for malignant transformation of OL. Collectively, these data indicated that TGM3 played an important role in OL malignant transformation and may serve as a predictor to identify OL with OSCC development.