Multiomics sequencing and immune microenvironment characteristics define three subtypes of small cell neuroendocrine carcinoma of the cervix.

Small cell cervical carcinoma (SCCC) is the most common neuroendocrine tumor in the female genital tract, with an unfavorable prognosis and lacking an evidence-based therapeutic approach. Until now, the distinct subtypes and immune characteristics of SCCC combined with genome and transcriptome have not been described. We performed genomic (n = 18), HPV integration (n = 18), and transcriptomic sequencing (n = 19) of SCCC samples. We assessed differences in immune characteristics between SCCC and conventional cervical cancer, and other small cell neuroendocrine carcinomas, through bioinformatics analysis and immunohistochemical assays. We stratified SCCC patients through non-negative matrix factorization and described the characteristics of these distinct types. We further validated it using multiplex immunofluorescence (n = 77) and investigated its clinical prognostic effect. We confirmed a high frequency of PIK3CA and TP53 alterations and HPV18 integrations in SCCC. SCCC and other small cell carcinoma had similar expression signatures and immune cell infiltration patterns. Comparing patients with SCCC to those with conventional cervical cancer, the former presented immune excluded or 'desert' infiltration. The number of CD8+ cells in the invasion margin of SCCC patients predicted favorable clinical outcomes. We identified three transcriptome subtypes: an inflamed phenotype with high-level expression of genes related to the MHC-II complex (CD74) and IFN-α/ß (SCCC-I), and two neuroendocrine subtypes with high-level expression of ASCL1 or NEUROD1, respectively. Combined with multiple technologies, we found that the neuroendocrine groups had more TP53 mutations and SCCC-I had more PIK3CA mutations. Multiplex immunofluorescence validated these subtypes and SCCC-I was an independent prognostic factor of overall survival. These results provide insights into SCCC tumor heterogeneity and potential therapies. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Hairpin-Empowered Invasive Reaction Combined with Catalytic Hairpin Assembly Cascade Amplification for the Specific Detection of Single-Nucleotide Polymorphisms.

Single-nucleotide polymorphism (SNP) is widely used in the study of disease-related genes and in the genetic study of animal and plant strains. Therefore, SNP detection is crucial for biomedical diagnosis and treatment as well as for molecular design breeding of animals and plants. In this regard, this article describes a novel technique for detecting SNP using flap endonuclease 1 (FEN 1) as a specific recognition element and catalytic hairpin assembly (CHA) cascade reaction as a signal amplification strategy. The mutant target (MT) was hybridized with a biotin-modified upstream probe and hairpin-type downstream probe (DP) to form a specific three-base overlapping structure. Then, FEN 1 was employed for three-base overlapping structure-specific recognition, namely, the precise SNP site identification and the 5' flap of DP dissociation. After dissociation, the hybridized probes were magnetically separated by a streptavidin-biotin complex. Especially, the ability to establish such a hairpin-type DP provided a powerful tool that could be used to hide the cut sequence (CS) and avoid false-positive signals. The cleaved CS initiated the CHA reaction and allowed superior fluorescence signal generation. Owing to the high specificity of FEN 1 for single base recognition, only the MT could be distinguished from the wild-type target and mismatched DNA. Owing to the dual signal amplification, as low as 0.36 fM MT and 1% mutation abundance from the mixtures could be detected, respectively. Furthermore, it could accurately identify SNPs from human cancer cells, as well as soybean leaf genome extracts. This strategy paves the way for the development of more precise and sensitive tools for diagnosing early onset diseases as well as molecular design breeding tools.

Rationally Designed Dual Base Pair Mismatch Enables Toehold-Mediated Strand Displacement to Efficiently Recognize Single-Nucleotide Polymorphism without Enzymes.

The efficiency of the enzyme-free toehold-mediated strand displacement (TMSD) technique is often insufficient to detect single-nucleotide polymorphism (SNP) that possesses only single base pair mismatch discrimination. Here, we report a novel dual base pair mismatch strategy enabling TMSD biosensing for SNP detection under enzyme-free conditions when coupled with catalytic hairpin assembly (CHA) and fluorescence resonance energy transfer (FRET). The strategy is based on a competitive strand displacement reaction mechanism, affected by the thermodynamic stability originating from rationally designed dual base pair mismatch, for the specific recognition of mutant-type DNA. In particular, enzyme-free nucleic acid circuits, such as CHA, emerge as a powerful method for signal amplification. Eventually, the signal transduction of this proposed biosensor was determined by FRET between streptavidin-coated 605 nm emission quantum dots (605QDs, donor) and Cy5/biotin hybridization (acceptor, from CHA) when incubated with each other. The proposed biosensor displayed high sensitivity to the mutant target (MT) with a detection concentration down to 4.3 fM and led to high discrimination factors for all types of mismatches in multiple sequence contexts. As such, the application of this proposed biosensor to investigate mechanisms of the competitive strand displacement reaction further illustrates the versatility of our dual base pair mismatch strategy, which can be utilized for the creation of a new class of biosensors.

Toward High-Quality Sulfide Solid Electrolytes: A Liquid-Phase Approach Featured with an Interparticle Coupled Unification Effect.

Sulfide solid electrolytes (SSEs) are highly wanted for solid-state batteries (SSBs). While their liquid-phase synthesis is advantageous over their solid-phase strategy in scalable production, it confronts other challenges, such as low-purity products, user-unfriendly solvents, energy-inefficient solvent removal, and unsatisfactory performance. This article demonstrates that a suspension-based solvothermal method using single oxygen-free solvents can solve those problems. Experimental observations and theoretical calculations together show that the basic function of suspension-treatment is "interparticle-coupled unification", that is, even individually insoluble solid precursors can mutually adsorb and amalgamate to generate uniform composites in nonpolar solvents. This anti-intuitive concept is established when investigating the origins of impurities in SSEs electrolytes made by the conventional tetrahydrofuran-ethanol method and then searching for new solvents. Its generality is supported by four eligible alkane solvents and four types of SSEs. The electrochemical assessments on the former three SSEs show that they are competitive with their counterparts in the literature. Moreover, the synthesized SSEs presents excellent battery performance, showing great potential for practical applications.

Metabolic engineering of Saccharomyces cerevisiae for de novo production of odd-numbered medium-chain fatty acids.

Odd-numbered fatty acids (FAs) have been widely used in nutrition, agriculture, and chemical industries. Recently, some studies showed that they could be produced from bacteria or yeast, but the products are almost exclusively odd-numbered long-chain FAs. Here we report the design and construction of two biosynthetic pathways in Saccharomyces cerevisiae for de novo production of odd-numbered medium-chain fatty acids (OMFAs) via ricinoleic acid and 10-hydroxystearic acid, respectively. The production of OMFAs was enabled by introducing a hydroxy fatty acid cleavage pathway, including an alcohol dehydrogenase from Micrococcus luteus, a Baeyer-Villiger monooxygenase from Pseudomonas putida, and a lipase from Pseudomonas fluorescens. These OMFA biosynthetic pathways were optimized by eliminating the rate-limiting step, generating heptanoic acid, 11-hydroxyundec-9-enoic acid, nonanoic acid, and 9-hydroxynonanoic acid at 7.83 mg/L, 9.68 mg/L, 9.43 mg/L and 13.48 mg/L, respectively. This work demonstrates the biological production of OMFAs in a sustainable manner in S. cerevisiae.

Accurate and Fast Prediction of Intrinsically Disordered Protein by Multiple Protein Language Models and Ensemble Learning.

Intrinsically disordered proteins (IDPs) play a vital role in various biological processes and have attracted increasing attention in the past few decades. Predicting IDPs from the primary structures of proteins offers a rapid and facile means of protein analysis without necessitating crystal structures. In particular, machine learning methods have demonstrated their potential in this field. Recently, protein language models (PLMs) are emerging as a promising approach to extracting essential information from protein sequences and have been employed in protein modeling to utilize their advantages of precision and efficiency. In this article, we developed a novel IDP prediction method named IDP-ELM to predict the intrinsically disordered regions (IDRs) as well as their functions including disordered flexible linkers and disordered protein binding. This method utilizes high-dimensional representations extracted from several state-of-the-art PLMs and predicts IDRs by ensemble learning based on bidirectional recurrent neural networks. The performance of the method was evaluated on two independent test data sets from CAID (critical assessment of protein intrinsic disorder prediction) and CAID2, indicating notable improvements in terms of area under the receiver operating characteristic (AUC), Matthew's correlation coefficient (MCC), and F1 score. Moreover, IDP-ELM requires solely protein sequences as inputs and does not entail a time-consuming process of protein profile generation, which is a prerequisite for most existing state-of-the-art methods, enabling an accurate, fast, and convenient tool for proteome-level analysis. The corresponding reproducible source code and model weights are available at https://github.com/xu-shi-jie/idp-elm.

Double base mismatches mediated catalytic hairpin assembly for enzyme-free single-base mutation detection: integrating signal recognition and amplification in one.

Single nucleotide polymorphism (SNP) biosensors are emerging rapidly for their promising applications in human disease prevention diagnosis, treatment, and prognosis. However, it remains a bottleneck in equipping simple and stable biosensors with the traits of high sensitivity, non-enzyme, and low cost. Double base mismatches mediated chain displacement reactions have attracted fascinating advantages of tailorable thermodynamics stability, non-enzyme, and excellent assembly compliance to involvement in SNP identification. As the base mismatch position and amount in DNA sequence can be artificially adjusted, it provides plenty of selectivity and specificity for exploring perfect biosensors. Herein, a biosensor with double base mismatches mediated catalytic hairpin assembly (CHA) is designed via one base mismatch in the toehold domain and the other base mismatch in the stem sequence of hairpin 1 (H1) by triggering CHA reaction to achieve selective amplification of the mutation target (MT) and fluorescence resonance energy transfer (FRET) effect that is composed of Cy3 and Cy5 terminally attached H1 and hairpin 2 (H2). Depending on the rationally designed base mismatch position and toehold length, the fabricated biosensors show superior SNP detection performance, exhibiting a good linearity with high sensitivity of 6.6 fM detection limit and a broad detection abundance of 1%. The proposed biosensor can be used to detect the KRAS mutation gene in real samples and obtain good recoveries between 106 and 116.99%. Remarkably, these extendible designs of base mismatches can be used for more types of SNP detection, providing flexible adjustment based on base mismatch position and toehold length variations, especially for their thermodynamic model for DNA-strand displacement reactions.

Characteristics of MK-801-induced locomotor sensitization.

Repeated administration of drugs of abuse leads to progressively greater behavioral responses; this phenomenon is referred to as behavioral sensitization. MK-801 blocks the N-methyl-d-aspartate (NMDA) receptor and elicits behavioral sensitization. Ketamine and phencyclidine, are also NMDA antagonists and have well-documented abuse potential. This study investigated the characteristics of MK-801-induced behavioral sensitization and found that it induced sensitization rapidly; only five consecutive treatments were required. The optimal dose for robust sensitization was also identified, which corresponded to the typical doses of abused NMDA antagonists (i.e., between the doses inducing antidepressant and anesthetic effects). Following MK-801-induced behavioral sensitization, changes were observed in the expression and/or phosphorylation of NMDA receptor subunits. While the expression of early growth response protein 1, which serves as a marker of neuronal activation, was affected by MK-801 sensitization, extracellular signal-regulated kinase phosphorylation was not associated with MK-801 treatment.

Triple Stimuli-Responsive Flexible Shape Memory Foams with Super-Amphiphilicity.

Highly porous multi-responsive shape memory foams have unique advantages in designing 3D materials with lightweight for varied applications. Herein, a facile and efficient approach to fabricating a thermo-, electro-, and photo-responsive shape memory composite foam is demonstrated. A specific multi-step carbonization protocol is adopted for transforming commercial melamine sponge (MS) to highly porous carbon foam (CF) with robust elastic resilience, efficient electrothermal/photothermal conversions, and super-amphiphilicity. It is a novel proposal for CF to take the dual role of the elastic supporting framework and 3D energy conversion/transmission network without any functional fillers. The composite foam cPCL@CF incorporates the CF skeleton with in situ crosslinked polycaprolactone (PCL) layers, which exhibits high conductivity (≈140 S m-1 ) and excellent light absorption (≈97.7%) in the range of 250-2500 nm. By triggering the crystalline transition of PCL, the composite foam displays sensitive electro- and photo-induced shape memory effect (SME) with outstanding shape fixation ratio (Rf ) and recovery ratio (Rr ). Thanks to the super-amphiphilicity and high electrical conductivity, the cPCL@CF composite foam can give rapid and distinguishable electric signals upon tiny drips of salt solutions or lithium-ion battery (LIB) electrolytes, making it a new type of sensor for detecting electrolyte leakage.

Infection of humanized mice with a novel phlebovirus presented pathogenic features of severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne emerging phlebovirus with high mortality rates of 6.0 to 30%. SFTSV infection is characterized by high fever, thrombocytopenia, leukopenia, hemorrhage and multiple organ failures. Currently, specific therapies and vaccines remain elusive. Suitable small animal models are urgently needed to elucidate the pathogenesis and evaluate the potential drug and vaccine for SFTSV infection. Previous models presented only mild or no pathogenesis of SFTS, limiting their applications in SFTSV infection. Therefore, it is an urgent need to develop a small animal model for the investigation of SFTSV pathogenesis and evaluation of therapeutics. In the current report, we developed a SFTSV infection model based on the HuPBL-NCG mice that recapitulates many pathological characteristics of SFTSV infection in humans. Virus-induced histopathological changes were identified in spleen, lung, kidney, and liver. SFTSV was colocalized with macrophages in the spleen and liver, suggesting that the macrophages in the spleen and liver could be the principle target cells of SFTSV. In addition, histological analysis showed that the vascular endothelium integrity was severely disrupted upon viral infection along with depletion of platelets. In vitro cellular assays further revealed that SFTSV infection increased the vascular permeability of endothelial cells by promoting tyrosine phosphorylation and internalization of the adhesion molecule vascular endothelial (VE)-cadherin, a critical component of endothelial integrity. In addition, we found that both virus infection and pathogen-induced exuberant cytokine release dramatically contributed to the vascular endothelial injury. We elucidated the pathogenic mechanisms of hemorrhage syndrome and developed a humanized mouse model for SFTSV infection, which should be helpful for anti-SFTSV therapy and pathogenesis study.

Engineering propionyl-CoA pools for de novo biosynthesis of odd-chain fatty acids in microbial cell factories.

Odd-chain fatty acids (OcFAs) and their derivatives have attracted great interest due to their wide applications in the food, pharmaceutical and petrochemical industries. Microorganisms can naturally de novo produce fatty acids (FAs), where mainly, even-chain with acetyl-CoA instead of odd-chain with propionyl-CoA is used as the primer. Usually, the absence of the precursor propionyl-CoA is considered the main reason that limits the efficient production of OcFAs. It is thus crucial to explore/evaluate/identify promising propionyl-CoA biosynthetic pathways to achieve large-scale biosynthesis of OcFAs. This review discusses the latest advances in microbial metabolism engineering toward producing propionyl-CoA and considers future research directions and challenges toward optimized production of OcFAs.

PPh3-Mediated Cascade Reaction of 2-Alkynylnitrobenzenes and Thioureas for the Construction of Imidazo[4,5-b]indole-2-thiones.

A simple method for the preparation of imidazo[4,5-b]indole-2-thiones from 2-alkynylnitrobenzenes and thioureas is described. In the reaction, a Wittig-like process was triggered by PPh3 and followed by a cyclization step. The products were afforded in yields of 70-98% under mild conditions. Additionally, the 2-alkynylnitrobenzenes were stable and could be prepared via a simple coupling step.

Total variation regularized expectation maximization reconstruction improves 68Ga-FAPI-04 PET/CT image quality as compared to ordered subset expectation maximization reconstruction.

BACKGROUND: This study aimed to investigate improvements in 68Ga-FAPI PET/CT image quality due to using total variation regularized expectation maximization (TVR-EM) and ordered subset expectation maximization (OS-EM) reconstruction. METHODS: Data from a total of 24 patients were retrospectively analyzed in this study. Positron emission tomography (PET) images were reconstructed using OS-EM and TVR-EM for 2 and 3 minutes-per-bed (min/bed) acquisition. The SUVmean of a region-of-interest on the liver, image noise, signal-to-noise ratios (SNR), the SUVmax of the lesions and the tumour-to-background ratios (TBR) were measured and compared between the 2 methods. Subjective image qualities were evaluated by two experienced radiologists using a 5-point score scale (5-excellent, 1-poor). RESULTS: In total, 132 lesions were analyzed. The image noise in TVR-EM reconstruction groups was lower than in the OS-EM groups (all P<0.05). The SNR, SUVmax of lesions and the TBR were higher for the TVR-EM reconstruction groups compared to OS-EM groups (all P<0.05). Also, the SUVmax of the lesions in the TVR-EM groups increased by at least 12% compared to OS-EM 3 min/bed group. The SUVmax for small (<10 mm) and large lesions (>10 mm) in the TVR-EM 2 min/bed group were significantly larger compared to the OS-EM 3 min/bed groups (all P<0.05). The highest image quality score resulted from the TVR-EM 3 min/bed group with a penalization factor of 0.25 (3.92±0.19). CONCLUSIONS: TVR-EM reduces image noise and improved the SNR, SUVmax and TBR of the lesions. It also enables fast acquisition without compromising image quality compared to standard OS-EM.

Multi-parametric Z-spectral MRI may have a good performance for glioma stratification in clinical patients.

OBJECTIVES: To comprehensively and noninvasively risk-stratify glioma grade, isocitrate dehydrogenase (IDH) genotype, and 1p/19q codeletion status using multi-contrast Z-spectral magnetic resonance imaging (MRI). METHODS: One hundred and thirteen patients with glioma were retrospectively included. Multiple contrasts contributing to Z-spectra, including direct saturation of water (DSW), semi-solid magnetization transfer contrast (MTC), amide proton transfer (APT) effect, aliphatic nuclear Overhauser effect, and the 2-ppm chemical exchange saturation transfer peak (CEST@2ppm), were fitted with five individual Lorentzian functions. Z-spectral contrasts were compared according to the three most important risk stratifications: tumor grade, IDH genotype, and 1p/19q codeletion status. We further investigated the differentiation of 1p/19q codeletion status within IDH mutant gliomas. The stratification performance of individual Z-spectral contrasts and their combination was quantified using receiver operating characteristic (ROC) analyses. RESULTS: DSW was significantly different within grade, IDH genotypes, and 1p/19q codeletion status. APT was significantly different with grade and IDH mutation, but not with 1p/19q subtypes. CEST@2ppm was only significantly different with 1p/19q codeletion subtypes. DSW and CEST@2ppm were the two Z-spectral contrasts able to differentiate 1p/19q codeletion subtypes within IDH mutant gliomas. For differentiating glioma grades using ROC analyses, DSW achieved the largest AUC. For differentiating IDH genotypes, DSW and APT achieved comparable AUCs. DSW was the best metric for differentiating 1p/19q codeletion status within all patients and within the IDH mutant patients. Combining all Z-spectral contrasts improved sensitivity and specificity for all risk stratifications. CONCLUSIONS: Multi-parametric Z-spectral MRI serves as a useful, comprehensive, and noninvasive imaging technique for glioma stratification in clinical patients. KEY POINTS: • Multiple contrasts contributing to Z-spectra were separately fitted with Lorentzian functions. • Z-spectral contrasts were compared within the three most important and common tumor risk stratifications for gliomas: tumor grade, IDH genotype, and 1p/19q codeletion status. • The stratification performance of individual Z-spectral contrasts and their combination was quantified using receiver operating characteristic analyses, which found Z-spectral MRI to be a useful and comprehensive imaging biomarker for glioma stratification.

Design, synthesis and biological evaluation of nitrofuran-1,3,4-oxadiazole hybrids as new antitubercular agents.

Three series of novel nitrofuran-1,3,4-oxadiazole hybrids were designed and synthesized as new anti-TB agents. The structure activity relationship study indicated that the linkers and the substituents on the oxadiazole moiety greatly influence the activity, and the substituted benzenes are more favoured than the cycloalkyl or heterocyclic groups. Besides, the optimal compound in series 2 was active against both MTB H37Rv strain and MDR-MTB 16883 clinical isolate and also displayed low cytotoxicity, low inhibition of hERG and good oral PK, indicating its promising potential to be a lead for further structural modifications.

Measurement of epicardial adipose tissue using non-contrast routine chest-CT: a consideration of threshold adjustment for fatty attenuation.

BACKGROUND: Epicardial adipose tissue (EAT) is known as an important imaging indicator for cardiovascular risk stratification. The present study aimed to determine whether the EAT volume (EV) and mean EAT attenuation (mEA) measured by non-contrast routine chest CT (RCCT) could be more consistent with those measured by coronary CT angiography (CCTA) by adjusting the threshold of fatty attenuation. METHODS: In total, 83 subjects who simultaneously underwent CCTA and RCCT were enrolled. EV and mEA were quantified by CCTA using a threshold of (N30) (- 190 HU, - 30 HU) as a reference and measured by RCCT using thresholds of N30, N40 (- 190 HU, - 40 HU), and N45 (- 190 HU, - 45 HU). The correlation and agreement of EAT metrics between the two imaging modalities and differences between patients with coronary plaques (plaque ( +)) and without plaques (plaque ( -)) were analyzed. RESULTS: EV obtained from RCCT showed very strong correlation with the reference (r = 0.974, 0.976, 0.972 (N30, N40, N45), P < 0.001), whereas mEA showed a moderate correlation (r = 0.516, 0.500, 0.477 (N30, N40, N45), P < 0.001). Threshold adjustment was able to reduce the bias of EV, while increase the bias of mEA. Data obtained by CCTA and RCCT both demonstrated a significantly larger EV in the plaque ( +) group than in the plaque ( -) group (P < 0.05). A significant difference in mEA was shown only by RCCT using a threshold of N30 (plaque ( +) vs ( -): - 80.0 ± 4.4 HU vs - 78.0 ± 4.0 HU, P = 0.030). The mEA measured on RCCT using threshold of N40 and N45 showed no significant statistical difference between the two groups (P = 0.092 and 0.075), which was consistent with the result obtained on CCTA (P = 0.204). CONCLUSION: Applying more negative threshold, the consistency of EV measurements between the two techniques improves and a consistent result can be obtained when comparing EF measurements between groups, although the bias of mEA increases. Threshold adjustment is necessary when measuring EF with non-contrast RCCT.

Applying a CT texture analysis model trained with deep-learning reconstruction images to iterative reconstruction images in pulmonary nodule diagnosis.

OBJECTIVE: To investigate the feasibility and accuracy of applying a computed tomography (CT) texture analysis model trained with deep-learning reconstruction images to iterative reconstruction images for classifying pulmonary nodules. MATERIALS AND METHODS: CT images of 102 patients, with a total of 118 pulmonary nodules (52 benign, 66 malignant) were retrospectively reconstructed with a deep-learning reconstruction (artificial intelligence iterative reconstruction [AIIR]) and a hybrid iterative reconstruction (HIR) technique. The AIIR data were divided into a training (n = 96) and a validation set (n = 22), and the HIR data were set as the test set (n = 118). Extracted texture features were compared using the Mann-Whitney U test and t-test. The diagnostic performance of the classification model was analyzed with the receiver operating characteristic curve (ROC), the area under ROC (AUC), sensitivity, specificity, and accuracy. RESULTS: Among the obtained 68 texture features, 51 (75.0%) were not influenced by the change of reconstruction algorithm (p > 0.05). Forty-four features were significantly different between benign and malignant nodules (p < 0.05) for the AIIR dataset, which were selected to build the classification model. The accuracy and AUC of the classification model were 92.3% and 0.91 (95% confidence interval [CI], 0.74-0.90) with the validation set, which were 80.0% and 0.80 (95% CI, 0.68-0.86) with the test set. CONCLUSION: With the CT texture analysis model trained with deep-learning reconstruction (AIIR) images showing favorable diagnostic accuracy in discriminating benign and malignant pulmonary nodules, it also has certain applicability to the iterative reconstruction (HIR) images.

Modular Assembly of Drug and Monodisperse SPIONs for Superior Magnetic and T2-Imaging Performance.

Development of superparamagnetic iron oxide nanoparticles (SPIONs) based theranostics has suffered due to its self-contradictory requirements on water dispersity and drug loadings. Generally well-dispersed SPIONs have excellent MRI performance but are insensitive to magnetism mediated delivery. Besides, loading hydrophobic drugs also hampers the stability of SPIONs which is critical for their biomedical applications. Considering these aspects, we employed curcumin as a cross-linking agent to facilitate the modular assembly of drug and monodisperse SPIONs (Cur/ALN-ß-CD-SPIONs). Interestingly, the saturation magnetization of Cur/ALN-ß-CD-SPIONs is higher than that of ALN-ß-CD-SPIONs, and the value of r2 indicating the negative contrast ability increases to 389.96 mM-1 s-1. Furthermore, the Cur/ALN-ß-CD-SPIONs are very stable in PBS buffer over 3 weeks. The mice treated with Cur/ALN-ß-CD-SPIONs by tail vein injection displayed a better tumor inhibition effect than that of free curcumin. This study provides a simple method for modular assembly of drug and monodisperse SPIONs, which is crucial to the design of SPIONs with superior T2-imaging performance and drug delivery.

Luminescence performance and vibronic behavior of Mn4+-activated Ca14-xKxAl10Zn6O35 deep-red phosphor.

In this study, a significant improvement of deep-red luminescence was successfully achieved via the substitution approach in the Mn4+-activated Ca14-xKxAl10Zn6O35 phosphor. The optimal Mn4+ doping level x was determined by studying luminescence concentration quenching behavior. The measured photoluminescence (PL) spectrum showed five distinct vibronic structures with the main peak centered at 712 nm. A theoretical simulation work was conducted for comparison, and the predominant phonon mode involving in the vibronic transition process was revealed. From the temperature-dependent PL spectra, an abnormal luminescence enhancement was observed at the temperature rising from T=100 to 340 K, and the underlying phonon-assisted luminescence mechanism was theoretically disclosed. Finally, we studied the temperature-dependent luminescence lifetime, and the primary phonon energy in the vibronic behavior was identified from the fitting work.

NSC23766 and Ehop016 Suppress Herpes Simplex Virus-1 Replication by Inhibiting Rac1 Activity.

Herpes simplex virus-1 (HSV-1) infection of the eyes leads to herpes simplex virus keratitis (HSK), the main cause of infectious blindness in the world. As the current therapeutics for HSV-1 infection are rather limited and prolonged use of acyclovir (ACV)/ganciclovir (GCV) and in immunocompromised patients lead to the rise of drug resistant mutants, it underlines the urgent need for new antiviral agents with distinct mechanisms. Our study attempted to establish ras-related C3 botulinum toxin substrate 1 (Rac1) as a new therapeutic target for HSV-1 infection by using Rac1-specific inhibitors to evaluate the in vitro inhibition of virus growth. Our results showed that increased Rac1 activity facilitated HSV-1 replication and inhibition of Rac1 activity by NSC23766 and Ehop016 significantly reduced HSV-1 replication. Thus, we identified NSC23766 and Ehop016 as possessing potent anti-HSV-1 activities by suppressing the Rac1 activity, suggesting that Rac1 is a potential target for treating HSV-1-related diseases.