Chemical Amplification-Enabled Topological Modification of Nucleic Acid Aptamers for Enhanced Cancer-Targeted Theranostics.

Site-specific chemical conjugation has long been a challenging endeavor in the field of ligand-directed modification to produce homogeneous conjugates for precision medicine. Here, we develop a chemical amplification-enabled topological modification (Chem-ATM) methodology to establish a versatile platform for the programmable modification of nucleic acid aptamers with designated functionalities. Differing from conventional conjugation strategies, a three-dimensional artificial base is designed in Chem-ATM as a chemical amplifier, giving access to structurally and functionally diversified conjugation of aptamers, with precise control over loading capacity but in a sequence-independent manner. Meanwhile, the sp3 hybridized atom-containing amplifier enables planar-to-stereo conformational transformation of the entire conjugate, eliciting high steric hindrance against enzymatic degradation in complex biological environments. The versatility of Chem-ATM is successfully demonstrated by its delivery of anticancer drugs and imaging agents for enhanced therapy and high-contrast noninvasive tumor imaging in xenograft and orthotopic tumor models. This study offers a different perspective for ligand-directed chemical conjugation to enrich the molecular toolbox for bioimaging and drug development.

Integrative conjugative elements mediate the high prevalence of tmexCD3-toprJ1b in Proteus spp. of animal source.

Integrative conjugative elements (ICEs) are important mobile elements that are associated with the dissemination of antibiotic resistance genes (ARGs) in Proteus. Recent studies demonstrated that the tigecycline resistance gene cluster tmexCD-toprJ has emerged in ICEs of Proteus. However, the prevalence of tmexCD-toprJ positive Proteus from animal sources is unclear. To cover the gap, a total of 762 Proteus spp. were isolated from animal source from six provinces of China to identify the tmexCD-toprJ positive isolates. Eight tmexCD-toprJ positive isolates were identified, with the tmexCD-toprJ positive rate of 1.05% against all Proteus spp. and 2.79% against ICE-bearing Proteus spp. The tmexCD-toprJ gene cluster in these Proteus spp. were tmexCD3-toprJ1b and all of them were carried by ICEs. Genetic structure analysis showed that tmexCD3-toprJ1b-bearing ICEs were complicated and plastic, but the tmexCD3-toprJ1b was specifically integrated into variable region III (VRIII) of ICEs with the help of integrases. Furthermore, we found that the umuC gene, which is presented in VRIII of ICEs and other genetic structures of many other bacterial genomes, was a hotspot for the integration of tmexCD-toprJ-bearing potential mobile elements. In summary, our results suggested that Proteus were important reservoirs for tmexCD-toprJ due to the high prevalence of ICEs. Therefore, continuous surveillance of ICEs-associated ARGs in Proteus is necessary and significant for controlling their future transmission. IMPORTANCE The emergence and spread of tmexCD-toprJ have greatly weakened the function of tigecycline. Although studies have demonstrated the significance of Proteus as carriers for tmexCD-toprJ, the epidemic mechanism and characteristics of tmexCD-toprJ in Proteus remain unclear. Herein, we deciphered that the umuC gene in VRIII of SXT/R391 ICEs was a hotspot for the integration of tmexCD3-toprJ1b-bearing mobile genetic elements by genomic analysis. The mobilization and dissemination of tmexCD3-toprJ1b in Proteus were mediated by highly prevalent ICEs. Furthermore, the co-occurrence of tmexCD3-toprJ1b-bearing ICEs with other chromosomally encoded multidrug resistance gene islands warned that the chromosomes of Proteus are significant reservoirs of ARGs. Overall, our results provide significant insights for the prevention and control of tmexCD3-toprJ1b in Proteus.

Long-term effects of vitamin D supplementation and maintaining sufficient vitamin D on knee osteoarthritis over 5 years.

OBJECTIVES: This study aimed to investigate the long-term effect of vitamin D supplementation compared to placebo over 5 years in participants with knee osteoarthritis (OA). We also aimed to describe the effect of maintaining sufficient serum vitamin D levels over five years in knee OA. METHODS: Participants (n = 173) from the Hobart centre of the Vitamin D Effects on Osteoarthritis (VIDEO) trial were extensively followed up 3 years after the cessation of 2-year investigational treatment. Participants were classified as maintaining sufficient vitamin D (n = 79) and not maintaining sufficient vitamin D (n = 61) groups. RESULTS: There was no significant difference in change in the knee symptoms, depression, and serum levels of IL6 and hs-CRP between both comparisons after 3 years of cessation of the clinical trial. However, among participants who reported no knee surgery (KS), there was a significant improvement in WOMAC function (ß: - 83.7, 95% CI: - 167.3, 0) and depression scores (ß: - 1.3, 95% CI: - 2.3, - 0.2) in vitamin D group compared to the placebo group. Similarly, those who maintained adequate vitamin D levels over 5 years had significantly less WOMAC knee pain (ß: - 33.9, 95% CI: - 65.7, - 2) and physical dysfunction (ß: - 105.5, 95% CI: - 198.2, - 12.8) than participants with vitamin D deficiency over 5 years. CONCLUSION: Vitamin D supplementation over 2 years or maintaining vitamin D sufficiency for 5 years was not associated with statistically significant differences in change in knee symptom scores over 5 years. However, among participants who did not report KS, 2-year vitamin D supplementation and maintaining sufficient vitamin D was linked to modest improvements in knee symptoms and depression scores in knee OA.

Characterisation of a Novel Tigecycline Resistance Gene tet(X22) and its Coexistence with blaNDM-1 in a Pseudomonas caeni Isolate.

OBJECTIVES: The emergence of pathogens that are resistant to both tigecycline and carbapenem poses a threat to public health globally. Continuous emergence of novel tet(X) variants accelerates the tigecycline resistance crisis. This study aimed to characterise the novel tigecycline resistance gene tet(X22) and its coexistence with carbapenem resistance gene blaNDM-1 in Pseudomonas caeni. METHODS: This P. caeni isolate co-harbouring tet(X22) and blaNDM-1 was systematically investigated using antimicrobial susceptibility testing, conjugation assays, genome sequencing, bioinformatic analyses, cloning of tet(X22) and functional analysis, and protein structure prediction. RESULTS: The carbapenem-resistant and tigecycline-resistant P. caeni isolate CE14 was obtained from chicken faeces in 2022. CE14 carried multiple antibiotic resistance genes, including the novel tet(X22) and blaNDM-1. Tet(X22) exhibited 64.72-90.48% amino acid identity with other variants [Tet(X) to Tet(X21)]. Cloning of the gene tet(X22) and protein structure prediction revealed that Tet(X22) confers resistance to tetracyclines, including tigecycline. tet(X22) and blaNDM-1 were located in two multidrug-resistant regions of the chromosome. CONCLUSIONS: The occurrence of the novel ISCR2-flanked tet(X22) in P. caeni suggests that the tet(X) variant has adapted to new hosts and may widely spread to further expand the host range. The future global spread of such pathogens co-harbouring tet(X) and blaNDM variants needs to be continuously monitored according to the One Health approach.

Optimized full CO2 photoreduction process by defective spinel atomic layers.

The impact of defects on the carbon dioxide (CO2) photoreduction property is sometimes contradictory. Herein, we employ two-dimensional materials, possessing high-density and high-uniformity active sites, as ideal models to thoroughly investigate the influence of defects on three main processes during CO2 photoreduction. As an example, oxygen-deficient ZnGa2O4 atomic layers are successfully fabricated, verified by the electron spin resonance spectra, X-ray photoelectron spectroscopy spectra and X-ray absorption near edge structure spectra. UV-vis diffuse reflectance spectra, photoluminescence spectra, surface photovoltage spectroscopy, N2 adsorption-desorption isotherm plots and density functional theory calculations indicate that the presence of oxygen defects helps to expand the photoabsorption, accelerate the carrier separation, and enhance the CO2 adsorption and protonation process. As a result, the carbon monoxide evolution rate of the defective ZnGa2O4 atomic layers was approximately 88 times higher than that of the ZnGa2O4 atomic layers under visible light irradiation. In other words, this work discloses that the introduction of defects on photocatalysts allows the optimization of the three primary processes, thus obtaining boosted CO2 photoreduction performance.

Clinicopathological features and differential diagnosis of gastric pleomorphic giant cell carcinoma.

The aim of this study was to investigate the clinicopathological features and differential diagnosis of gastric pleomorphic giant cell carcinoma. Histopathology, immunohistochemistry, and human epidermal growth factor receptor 2 (HER2) gene testing were conducted for seven cases of gastric pleomorphic giant cell carcinoma. In histomorphological terms, all seven cases involved pleomorphic giant cell carcinoma, accounting for more than 10% of the entire tumor, with pleomorphic spindle cells and giant cells mixed with various histomorphological structures of adenocarcinoma with high, intermediate, and low differentiation. There was large heterogeneity in the HER2 protein expression and HER2 gene amplification in the gastric pleomorphic giant cell carcinoma, and both levels of HER2 were focal in three cases, accounting for 42.9% (3/7). The mismatch repair gene proteins MLH1, MSH2, PMS2, and MSH6 were positive. Routine immunohistochemical markers, i.e., pan-cytokeratin, epithelial membrane antigen, villin, caudal-type homeobox 2, E-cadherin, and p53, were positive in the gastric pleomorphic giant cell carcinoma, while vimentin, calponin, smooth muscle actin, nestin, S-100, cluster of differentiation (CD) 99, desmin, and CD34 were focally expressed in both the spindle and the giant cells, with Ki-67-positive cells accounting for 70-80%. Gastric pleomorphic giant cell carcinoma presents multiple histomorphological features and is easily confused with various tumors. Clarifying the histopathological features of this type of tumor is important for differential diagnosis and precise treatment.

Dual-functional single-atomic Mo/Fe clusters-decorated C3N5 via three electron-pathway in oxygen reduction reaction for tandemly removing contaminants from water.

Inspired by the development of single-atom catalysts (SACs), the fabrication of multimetallic SACs can be a promising technical approach for the in situ electro-Fenton (EF) process. Herein, dual-functional atomically dispersed Mo-Fe sites embedded in carbon nitride (C3N5) (i.e., MoFe/C3N5) were synthesized via a facile SiO2 template method. The atomically isolated bimetallic configuration in MoFe/C3N5 was identified by combining the microscopic and spectroscopic techniques. The MoFe/C3N5 catalyst on the cathode exhibited a remarkable catalytic activity toward the three electron-dominated oxygen reduction reaction in sodium sulfate, leading to a highly effective EF reaction with a low overpotential for the removal of organic contaminants from wastewater. The new catalyst showed a superior performance over its conventional counterparts, owing to the dual functions of the dual-metal active sites. Density functional theory (DFT) analysis revealed that the dual-functional 50-MoFe/C3N5 catalyst enabled a synergistic action of the Mo-Fe dual single atomic centers, which can alter the adsorption/dissociation behavior and decrease the overall reaction barriers for effective organic oxidation during the EF process. This study not only sheds light on the controlled synthesis of atomically isolated catalyst materials but also provides deeper understanding of the structure-performance relationship of the nanocatalysts with dual active sites for the catalytic EF process. Additionally, the findings will promote the advanced catalysis for the treatment of emerging organic contaminants in water and wastewater.

Atomically Dispersed Mg-N-C Material Supported Highly Crystalline Pt3Mg Nanoalloys for Efficient Oxygen Reduction Reaction.

Single-atom or atomically dispersed metal materials have emerged as highly efficient catalysts, but their potential as excellent supports has rarely been reported. In this work, we prepared Mg-N-C materials derived from annealing of a Mg-based metal-organic framework (MOF). By introducing Pt, Mg-N-C not only serves as a platform for anchoring Pt nanoparticles but also facilitates the integration of Mg into the Pt face-centered cubic lattice, resulting in the formation of highly crystalline Pt3Mg nanoalloys via the metal-support interfacial interaction. Synchrotron radiation-based X-ray absorption spectroscopy (XAS) enables us to study the interfacial interaction and the surface electronic structure of this intricate system. The formation of Pt3Mg nanoalloys induces a downshift of the Pt d-band (gaining d-charge), as revealed by the decrease in the Pt L3-edge white-line (WL) area under the curve. This downshift can weaken the binding of oxygen reduction reaction (ORR) intermediates, hence improving the ORR performance.

The characteristics of mcr-bearing plasmids in clinical Salmonella enterica in Sichuan, China, 2014 to 2017.

Salmonella is one of the most important zoonotic pathogens and a major cause of foodborne illnesses, posing a serious global public health hazard. The emergence of plasmid-mediated mcr genes in Salmonella has greatly reduced the clinical choice of salmonellosis treatment. The aim of this study was to investigate the plasmid characteristics of mcr-positive Salmonella identified from patients in Sichuan, China during 2014 to 2017 by whole genomes sequencing. In this study, a total of 12 mcr-positive isolates (1.15%, ; mcr-1, n=10; mcr-3, n=2) were identified from 1046 Salmonella isolates using PCR. Further characterization of these isolates was performed through antimicrobial susceptibility testing, conjugation assays, whole genome sequencing, and bioinformatics analysis. The mcr-1 gene in these isolates were carried by three types of typical mcr-1-bearing plasmids widely distributed in Enterobacteriaceae (IncX4, IncI2 and IncHI2). Of note, two mcr-1-harboring IncHI2 plasmids were integrated into chromosomes by insertion sequences. Two mcr-3-bearing plasmids were IncC and IncFIB broad-host-range plasmids respectively. Genetic context analysis found that mcr-1 was mainly located in Tn6330 or truncated Tn6300, and mcr-3 shared a common genetic structure tnpA-mcr-3-dgkA-ISKpn40. Overall, we found that mcr gene in clinical Salmonella were commonly carried by broad-host plasmids and have potential to transfer into other bacteria by these plasmids. Continuous surveillance of MDR Salmonella in humans and investigation the underlying transmission mechanisms of ARGs are vital to curb the current severe AMR concern.

Comparative analysis of anchorage strength and histomorphometric changes after implantation of miniscrews in adults and adolescents: an experimental study in Beagles.

OBJECTIVES: This study aimed to explore the differences in anchorage strength and histomorphometric changes in orthodontic miniscrews between adult and adolescent beagles. MATERIAL AND METHOD: Six adult beagles and six young beagles were used as experimental subjects, and eight miniscrews were symmetrically placed in the posterior mandible of each dog. Measurement of the displacement (mm) of two adjacent miniscrews after load application was performed to compare the anchorage strength between the adult and adolescent groups. Three intravital bone fluorochromes (oxytetracycline, calcein green, xylenol orange) were administered postoperatively to mark the active bone-forming surface. Subsequently, the mineral apposition rate and bone-implant contact ratio were measured for dynamic and static histomorphometry. Finally, the expression levels of the RANKL/OPG ratio were evaluated by immunohistochemistry. RESULTS: The average displacement of miniscrews in the adult group was significantly less than that in the adolescent group after load application. For histomorphometry analysis, the mineral exposure rate in the adolescent group was higher than that in the adult group with or without force application. In addition, more fractures and new bone formation but deceased bone-implant contact ratios were observed in the adolescent group than in the adult group. The ratio of RANKL/OPG expression increased more in the adolescent group than in the adult group. CONCLUSION: Miniscrews do not remain in the same position as skeletal anchors, and the amount of displacement was higher in adolescent group than that in adult group, reflecting the weaker anchorage strength of miniscrews in adolescents due to the higher bone turnover rate and active bone remodelling. Therefore, it is feasible to apply orthodontic loading to the miniscrews in adult patients earlier, even immediately, but it is recommended to wait a period for the adolescents.

The influence of permeability and heterogeneity on chemical flooding efficiency and remaining oil distribution-based on NMR displacement imaging.

To investigate the impact of permeability and heterogeneity on oil displacement efficiency and remaining oil distribution of chemical flooding, three groups of high and ultrahigh permeability core samples from an ultrahigh water-cut oilfield in western China were selected as the research objects in this study. High-pressure mercury injection, scanning electron microscopy, wettability test, and other methods were used to characterize the reservoir properties of core samples. Six groups of experiments were performed using the nuclear magnetic resonance (NMR) displacement imaging technology to simulate the oilfield development process considering the economic benefits. The displacement stage with the best oil displacement effect in the process of waterflooding, chemical flooding and then waterflooding was defined, and the control effect of permeability and heterogeneity on the improvement of oil displacement efficiency by polymer-surfactant binary flooding was discussed. The distribution position of remaining oil in different displacement stages was quantitatively and visually displayed, and its control factors were revealed. The research shows that during the simulation process of first waterflooding followed by chemical flooding and then waterflooding in the oilfield, the T2 spectrum signal amplitude increases the most in the two stages, one is from saturated oil flooding to 50% water cut and the other one is from 95% water cut to the end of 1 PV polymer flooding. The oil displacement efficiency increases the most, and the oil is primarily discharged from pore throats larger than 90 ms (or with pore throat radius of 8.37 µm). Compared with heterogeneity, permeability plays a more obvious controlling role in improving the oil displacement efficiency of polymer-surfactant binary flooding. The influence of fingering phenomenon on the distribution of remaining oil is most obvious in the second waterflooding, and the distribution of remaining oil with polymer slug is more obviously affected by the fingering phenomenon than that with polymer-surfactant slug. The study results provide theoretical guidance for tapping the remaining oil potential of old oilfields with high to ultrahigh permeabilities.

Chemical recycling of polyolefins: a closed-loop cycle of waste to olefins.

The unsuitable disposal of plastic wastes has caused serious environmental pollution, and finding a green manner to address this problem has aroused wide concern. Plastic wastes, especially polyolefin wastes, are rich in carbon and hydrogen, and chemical recycling shows distinct advantages in their conversion into olefins and realizes a closed-loop cycling of plastic wastes. Plastic wastes should be labeled before disposal. The necessity for, and methods of, pretreatment are introduced in this paper and the whole recycling process of polyolefin wastes is also summarized. As the core technology pyrolysis, including thermal, catalytic and solvolysis processes, is introduced in detail due to its potential for future development. We also briefly describe the feasible strategies of pyrolytic oil refining and life cycle assessment of the chemical recycling process. In addition, suggestions and perspectives concerning the industrial improvement of polyolefin chemical recycling are proposed.

Dynamic risk assessment of urban flood disasters based on functional area division-A case study in Shenzhen, China.

The assessment of urban flood risk plays a vital role in disaster prevention and mitigation. This work aims to assess the dynamic risk of urban flood triggered by population movements through dividing urban functional zoning from the perspective of collective cognition. Firstly, the urban functional areas are identified using Points of Interest data and then the population movements mobile is detected based on functional areas using mobile signaling big data. Then, one-dimensional and two-dimensional hydrodynamic models are employed to simulate the 50-year flood scenario in Futian District, Shenzhen. Finally, a spatio-temporal dynamic assessment model for urban flood risk is constructed based on the extent of inundation, water depth, population density, and the disaster-bearing capacity of functional areas. The research findings are as follows: (1) Futian District's urban planning showcases harmonious integration of single-function and mixed-function areas. Utilizing the 50% perception standard efficiently identifies distinct functional types across diverse urban zones. The results are highly consistent with the actual situation. (2) During morning peak hours, the population exhibits a nuanced pattern of dispersal, concentration, and transition. Lunchtime witnesses multiple central clusters forming and gradually dispersing, while the evening peak witnesses population regrouping, covering broader geographical extents. Dynamic utilization of functional areas and mobile phone signaling data outperforms static population metrics, offering deeper insights into the complexities of human activity. (3) Between 12:00 and 13:00, lunchtime movements lead to a surge of 6 high-risk zones in the central area and 5 in the Meiling area. The dynamic flood risk assessment model, based on functional area delineation, effectively identifies disparities and fluctuations in flood risk across diverse functional areas during rainfall scenarios, ensuring heightened precision and accuracy in risk assessment.

Baseline and early changes in the neutrophil-lymphocyte ratio (NLR) predict survival outcomes in advanced colorectal cancer patients treated with immunotherapy.

BACKGROUND: Systemic inflammation plays a role in carcinogenesis and is related to overall survival in patients with different cancer types, including those treated with immune checkpoint blockade (ICB). The neutrophil-lymphocyte ratio (NLR) is calculated by circulating neutrophil to lymphocyte counts, which represents an indicator of the balance between the deleterious roles of neutrophilia and the beneficial roles of lymphocyte-mediated immunity. We hypothesized that the NLR may predict outcomes in metastatic colorectal cancer (mCRC) patients treated with immunotherapy. MATERIALS AND METHODS: This retrospective study included 110 mCRC patients who were treated with immunotherapy at Sun Yat-sen University Cancer Center. Several inflammatory biomarkers were measured at baseline and after two cycles of treatment. The X-tile program was used to obtain the cutoff values. We examined the impact of both baseline and posttreatment inflammatory index levels on overall survival (OS). RESULTS: In univariate analysis, both a low baseline NLR (P = 0.014) and a decreased NLR after 2 cycles of immunotherapy (P < 0.001) were considerably correlated with better OS. In multivariate analysis, age, liver metastasis, baseline lymphocyte-monocyte ratio (LMR), baseline NLR and early changes in NLR independently predicted OS. Patients with both a low baseline NLR and an early NLR reduction had the longest OS (median, 29.63 months). The best outcomes were remarkably observed in patients who had both an early NLR reduction and a high tumor mutational burden (TMB) (≥10 mut/Mb) (P < 0.0001). CONCLUSIONS: Both a low baseline NLR and an early NLR reduction are significantly associated with a better prognosis in mCRC patients treated with immunotherapy. Further analysis indicated that the combination of NLR and TMB could obtain additional predictive power.

Rapid chiral purity identification of mandelic acid by Raman spectra in the O-H stretching region.

Chiral molecules play a very important role in biological systems, and more and more chiral drugs are used in the treatment of diseases. Mandelic acid (MA) is an important chiral starting substance or the key intermediate of some chiral drugs, and the rapid detection of its chiral purity is very important in the synthesis, separation and detection of drugs. In this study, we developed a method for rapid determination of chiral purity of MA by Raman spectroscopy, and measured a series of Raman spectra of different chiral MA. Through the analysis, it is found that the OH stretching vibration peak can be used to identify the components of chiral molecules, and the enantiomeric excess (ee value) obtained is in good agreement with the real value, and the error is about 5%. The experimental detection speed is fast and the efficiency is high. Our work firstly provides a new idea for the purity detection of chiral molecules by the original Raman spectrum.

The characteristic of competitive adsorption of HCHO and C6H6 on activated carbon by molecular simulation.

To explore the characteristic of competitive adsorption of formaldehyde (HCHO) and benzene(C6H6) on activated carbon, the slit models of activated carbon with different pore sizes of 1 nm, 2 nm and 4 nm were constructed by using the Visualizer module of Materials Studio molecular simulation software. The adsorption of single-component C6H6 and HCHO at three different temperatures of 288.15K,293.15K and 323.15K were conducted by the method of grand canonical Monte Carlo. Experiments were carried out to verify the accuracy of simulation results. For the single-compound adsorption, the adsorption amount of C6H6 varied little at different temperature conditions, while the pore size had a significant effect on the adsorption amount of C6H6, and the adsorption capability increased as the pore size goes up. The adsorption capacity of HCHO decreased as the temperature goes up, and the adsorption capacity of both 1 nm and 4 nm pore size activated carbon was less than that of 2 nm pore size. As for the competitive adsorption, HCHO has a better adsorption effect by activated carbon when the pore is in small size like 1 nm, while the competitive adsorption ability of C6H6 is much better than HCHO as the pore size goes up to 2 nm or 4 nm.Implications: (1) Understanding the equilibrium process of activated carbon adsorption at the molecular level based on the co-existence of multi-component VOCs. (2) The effects of concentration, temperature and humidity factors on the coupling of the dynamic equilibrium of competing adsorption of benzene and formaldehyde were analyzed. (3) The accuracy of the molecular simulations was verified using an experimental approach.

Modulation of Radical Intermediates in Rechargeable Organic Batteries.

Organic materials have been considered as promising electrodes for next-generation rechargeable batteries in view of their sustainability, structural flexibility, and potential recyclability. The radical intermediates generated during the redox process of organic electrodes have profound effect on the reversible capacity, operation voltage, rate performance, and cycling stability. However, the radicals are highly reactive and have very short lifetime during the redox of organic materials. Great efforts have been devoted to capturing and investigating the radical intermediates in organic electrodes. Herein, this review summarizes the importance, history, structures, and working principles of organic radicals in rechargeable batteries. More importantly, challenges and strategies to track and regulate the radicals in organic batteries are highlighted. Finally, further perspectives of organic radicals are proposed for the development of next-generation high-performance rechargeable organic batteries. This article is protected by copyright. All rights reserved.

Simultaneous Quantification and Visualization of Photosynthetic Pigments in Lycopersicon esculentum Mill. under Different Levels of Nitrogen Application with Visible-Near Infrared Hyperspectral Imaging Technology.

Leaf photosynthetic pigments play a crucial role in evaluating nutritional elements and physiological states. In facility agriculture, it is vital to rapidly and accurately obtain the pigment content and distribution of leaves to ensure precise water and fertilizer management. In our research, we utilized chlorophyll a (Chla), chlorophyll b (Chlb), total chlorophylls (Chls) and total carotenoids (Cars) as indicators to study the variations in the leaf positions of Lycopersicon esculentum Mill. Under 10 nitrogen concentration applications, a total of 2610 leaves (435 samples) were collected using visible-near infrared hyperspectral imaging (VNIR-HSI). In this study, a "coarse-fine" screening strategy was proposed using competitive adaptive reweighted sampling (CARS) and the iteratively retained informative variable (IRIV) algorithm to extract the characteristic wavelengths. Finally, simultaneous and quantitative models were established using partial least squares regression (PLSR). The CARS-IRIV-PLSR was used to create models to achieve a better prediction effect. The coefficient determination (R2), root mean square error (RMSE) and ratio performance deviation (RPD) were predicted to be 0.8240, 1.43 and 2.38 for Chla; 0.8391, 0.53 and 2.49 for Chlb; 0.7899, 2.24 and 2.18 for Chls; and 0.7577, 0.27 and 2.03 for Cars, respectively. The combination of these models with the pseudo-color image allowed for a visual inversion of the content and distribution of the pigment. These findings have important implications for guiding pigment distribution, nutrient diagnosis and fertilization decisions in plant growth management.

Overexpression of ZEB1 and YAP1 is related to poor prognosis in patients with gliomas with different IDH1 status.

OBJECTIVE: Whether there is a correlation between zinc-finger E-box-binding homolog 1 (ZEB1) and Yes-associated protein 1 (YAP1) with clinical outcome in gliomas remains unclear. Hence, this study aimed to investigate the effects of ZEB1 and YAP1 on the prognosis of human gliomas and its relationship with the isocitrate dehydrogenase 1 (IDH1) gene state. METHODS: Immunohistochemical staining was used to record the expression levels of ZEB1, YAP1, and p-YAP1 in 122 cases of low-grade glioma (LGGs) and 69 cases of glioblastoma (GBMs). The correlations of ZEB1 and YAP1 with pathological data were determined by Pearson's Chi-square test. Spearman correlation analysis was then used for analyzing the relationship among YAP1, ZEB1, and IDH1 gene status. The effects of ZEB1 and YAP1 on prognosis were investigated through survival analysis. RESULTS: We detected high ZEB1 expression levels in 29 LGGs (23.8%) and 39 GBMs (56.5%), and high YAP1 expression levels in 22 LGGs (18.0%) and 44 of GBM (63.8%). These results revealed that the protein expression levels of ZEB1 and YAP1 were higher in GBM (P < 0.001). There was a significantly positive correlation between ZEB1 and YAP1 (P < 0.001; r = 0.533). High ZEB1 expression was related to tumor grade (P < 0.001) and Ki-67 (P = 0.0037). YAP1 overexpression was correlated with Ki-67 (P < 0.001), P53 (P = 0.009), tumor grade (P < 0.001), and tumor location (P = 0.018). Patients with ZEB1 and YAP1 high expression had worse overall survival (OS) (P < 0.001). The multivariate analysis showed that YAP1 was an independent prognostic factor for OS. In the LGG group, worse OS were observed in glioma patients with elevated YAP1 expression level. Spearman correlation analysis revealed no association between ZEB1 expression and IDH1 state (P = 0.360; r = -0.084), and YAP1 expression had a negative correlation with IDH1 mutation (P < 0.001, r = -0.364). CONCLUSIONS: Our study showed that ZEB1 and YAP1 were significantly activated in GBM, and patients with high ZEB1 and YAP1 expression had worse OS. ZEB1 expression was significantly correlated with YAP1 in glioma. ZEB1 and YAP1 coexpression may serve as a useful prognostic biomarker for glioma, and aberrant YAP1 expression may be associated with IDH1 gene state.

Structural-Activity Relationship-Inspired the Discovery of Saturated Fatty Acids as Novel Colistin Enhancers.

The emergence and prevalence of mobile colistin resistance gene mcr have dramatically compromised the clinical efficacy of colistin, a cyclopeptide antibiotic considered to be the last option for treating different-to-treat infections. The combination strategy provides a productive and cost-effective strategy to expand the lifespan of existing antibiotics. Structural-activity relationship analysis of polymyxins indicates that the fatty acyl chain plays an indispensable role in their antibacterial activity. Herein, it is revealed that three saturated fatty acids (SFAs), especially sodium caprate (SC), substantially potentiate the antibacterial activity of colistin against mcr-positive bacteria. The combination of SFAs and colistin effectively inhibits biofilm formation and eliminates matured biofilms, and is capable of preventing the emergence and spread of mobile colistin resistance. Mechanistically, the addition of SFAs reduces lipopolysaccharide (LPS) modification by simultaneously promoting LPS biosynthesis and inhibiting the activity of MCR enzyme, enhance bacterial membrane damage, and impair the proton motive force-dependent efflux pump, thereby boosting the action of colistin. In three animal models of infection by mcr-positive pathogens, SC combined with colistin exhibit an excellent therapeutic effect. These findings indicate the therapeutic potential of SFAs as novel antibiotic adjuvants for the treatment of infections caused by multidrug-resistant bacteria in combination with colistin.