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Objectives: To examine the correlation of apparent diffusion coefficient (ADC), diffusion weighted imaging (DWI), and T1 contrast enhanced (T1-CE) with Ki-67 in primary central nervous system lymphomas (PCNSL). And to assess the diagnostic performance of MRI radiomics-based machine-learning algorithms in differentiating the high proliferation and low proliferation groups of PCNSL., Methods: 83 patients with PCNSL were included in this retrospective study. ADC, DWI and T1-CE sequences were collected and their correlation with Ki-67 was examined using Spearman's correlation analysis. The Kaplan-Meier method and log-rank test were used to compare the survival rates of the high proliferation and low proliferation groups. The radiomics features were extracted respectively, and the features were screened by machine learning algorithm and statistical method. Radiomics models of seven different sequence permutations were constructed. The area under the receiver operating characteristic curve (ROC AUC) was used to evaluate the predictive performance of all models. DeLong test was utilized to compare the differences of models., Results: Relative mean apparent diffusion coefficient (rADCmean) (ρ=-0.354, p = 0.019), relative mean diffusion weighted imaging (rDWImean) (b = 1000) (ρ = 0.273, p = 0.013) and relative mean T1 contrast enhancement (rT1-CEmean) (ρ = 0.385, p = 0.001) was significantly correlated with Ki-67. Interobserver agreements between the two radiologists were almost perfect for all parameters (rADCmean ICC = 0.978, 95%CI 0.966-0.986; rDWImean (b = 1000) ICC = 0.931, 95% CI 0.895-0.955; rT1-CEmean ICC = 0.969, 95% CI 0.953-0.980). The differences in PFS (p = 0.016) and OS (p = 0.014) between the low and high proliferation groups were statistically significant. The best prediction model in our study used a combination of ADC, DWI, and T1-CE achieving the highest AUC of 0.869, while the second ranked model used ADC and DWI, achieving an AUC of 0.828., Conclusion: rDWImean, rADCmean and rT1-CEmean were correlated with Ki-67. The radiomics model based on MRI sequences combined is promising to distinguish low proliferation PCNSL from high proliferation PCNSL., Competing Interests: Declarations. Ethics approval and consent to participate: This retrospective study was approved by the Ethics Committee of the Shandong Provincial Hospital and written informed consent for the participants over 16 years of age was discarded because of the retrospective nature of this study. For participants less than 16 years of age, written informed consent has been obtained from their parents/guardians after a brief description of the purpose and objectives of the study has been given to them. We confirmed that the study was carried out in accordance with relevant guidelines and regulations of Helsinki Declaration. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Clinical trial number: Not applicable., (© 2025. The Author(s).)

As an important physiological indicator, wheat canopy temperature (CT) can be observed after flowering in an attempt to predict wheat yield and quality. However, the relationship between CT and wheat yield and quality is not clear. In this study, the CT, photosynthetic rate (Pn), filling rate, wheat yield, and wheat quality of 68 wheat lines were measured, in an attempt to establish a connection between CT and yield and quality and accelerate the selection of new varieties. This experiment used an infrared imaging camera to measure the CT of wheat materials planted in the field in 2022. Twenty materials with significant temperature differences were selected for planting in 2023. By comparing the temperature trends in 2022 and 2023, it is believed that materials 4 and 13 were cold-type materials, while materials 3 and 11 were warm-type materials. The main grain filling period of cold-type materials occurs in the middle and late stages of the grain filling period and the Pn and the thousand-grain weights of cold-type materials were higher than those of warm-type materials. Similarly, under continuous rainy conditions, cold-type materials had a higher protein and wet gluten contents, while warm-type materials had higher sedimentation values and shorter formation times.

It is vital to measure combustion temperature to define combustion models accurately. For single fuel particles in powder-fueled ramjets, their size distribution ranges from submicron to submillimeter, and their burn time is short to millisecond order. Moreover, the radiation intensity of different types of fuel particles significantly oscillated with several orders of magnitude. Current temperature measurement technology is facing this challenge. This paper proposes a highly spatiotemporal resolved pyrometry to measure the combustion temperature of fuel particles by coupling single-point photomultiplier tube (PMT)-based and two-dimensional complementary metal oxide semiconductor (CMOS)-based photoelectric devices. Both the offline calibration by blackbody furnace and online calibration by standard lamp confirmed the measurement accuracy of the pyrometry. Then, the pyrometry was used to measure the combustion temperature of fuel particles including micro-Al, nano-Al, micro-Mg, nano-B, and micro-B 4 C. The temperature evolution and distribution of burning fuel particles were complementarily obtained, especially the interfacial flame temperature near the particle surface. Based on the obtained combustion temperature, the combustion characteristics and the energy release efficiencies among these fuels were evaluated and compared in detail, which are helpful to recognize, in depth, the combustion behavior and reveal the combustion mechanism of fuel particles in powder-fueled ramjets.

Silk protein, as a natural polymer material with unique structures and properties, exhibits tremendous potential in the biomedical field. Given the limited production and restricted properties of natural silk proteins, molecular biotechnology has been extensively applied in silk protein genetic engineering to produce novel silk proteins with specific properties. This review outlines the roles of major model organisms, such as silkworms and spiders, in silk protein production, and provides a detailed introduction to the applications of gene editing technologies (eg, CRISPR-Cas9), transgenic expression technologies, and synthetic biology techniques in silk protein genetic engineering. By analyzing the genetic factors influencing silk protein expression, this review further elaborates on the innovative applications of silk proteins in drug delivery systems, tissue engineering and regenerative medicine (eg, skin, bone, cartilage, and vascular repair), as well as antibacterial immune strategies. Notably, modified silk proteins expressed by transgenic silkworms demonstrate significant advantages in enhancing drug bioavailability and promoting cell proliferation and differentiation. In conclusion, silk protein gene engineering, through continuous innovations in molecular biotechnology, has provided an effective pathway for the production of high-performance silk protein materials. The extensive applications of these modified silk proteins in the biomedical field have not only expanded the functionality of silk proteins but also offered new approaches to address medical challenges. In the future, the development of silk protein gene engineering will further rely on interdisciplinary integration to promote in-depth research and the expansion of industrial applications of silk proteins., Competing Interests: The authors declare no competing interests in this work., (© 2025 Ji et al.)

Freshwater fungi consist of a highly diverse group of organisms in freshwater habitats worldwide. During a survey of fungal diversity in freshwater habitats across different regions of Jiangxi Province, China, four freshwater fungi were collected. To study their phylogenetic relationships, the internal transcribed spacer (ITS1-5.8S-ITS2), large subunit (28S, LSU), small subunit (18S, SSU), and RNA polymerase II subunit ( RPB2 ) genes were selected for phylogenetic analyses. Based on morphology coupled with phylogenetic analysis, these strains were confirmed to belong to Phaeoisaria , Pleurothecium , and Pseudodactylaria . Among them, three fungi were confirmed as the new species, namely, Pleurothecium lignicola (Pleurotheciaceae), Pseudodactylaria jiangxiensis ( Pseudodactylariaceae ), and Ps. lignicola (Pseudodactylariaceae). One species was identified as Phaeoisaria filiformis (Pleurotheciaceae), a new record of this species in China. All species were compared with other similar species, and detailed descriptions, illustrations, and phylogenetic data were provided.

Background: Remimazolam is a benzodiazepine sedative that is indicated for induction and maintenance during general anaesthesia. Remimazolam is also used for sedation in outpatient surgery; however, most reports have focused on nonelderly patients, whereas only a few studies have reported the use of remimazolam for elderly patients when receiving regional nerve block anaesthesia., Aim: The aim of this study was to evaluate the effects of different doses of remimazolam in elderly patients when specifically related to regional nerve block anaesthesia., Methods: This study was conducted at a university hospital between February 2022 and March 2023. We included 80 patients aged 65 years or older under regional nerve block anaesthesia. After the effects of anaesthesia were determined, patients were intravenously administered different doses of the test drug, i.e. 4, 4.5, 5, 5.5, or 6 mg, which were named the R1, R2, R3, R4, and R5 groups, respectively. The primary outcome was the loss of consciousness time. The secondary outcomes included the maintenance time and the number of assisted ventilators needed. The exceptional response of patients in terms of loss of consciousness maintenance time, the mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), SpO 2 , and modified observers assessment of alertness/sedation (MOAA/S) scores were recorded at baseline (T0), 3 min after the injection of the test drug (T1), 6 min after the injection of the test drug (T2), 9 min after the injection of the test drug (T3), 12 min after the injection of the test drug (T4), 15 min after the injection of the test drug (T5), 18 min after the injection of the test drug (T6), 21 min after the injection of the test drug (T7), and 24 min after the injection of the test drug (T8)., Results: We included 80 patients according to the inclusion and exclusion criteria, with 16 patients in each group. There were no significant differences in sex, age, and BMI amongst the 5 groups. The loss of consciousness time was significantly greater in the R2 group than in the R3, R4, and R5 groups (p < 0.001), and the loss of consciousness maintenance time was significantly greater in the R5 group than in the R3 group (p < 0.05). The MAP was significantly lower in the R2 and R5 groups than in the R1 group at T4 (p = 0.004) and significantly lower in the R5 group than in the R1 group at T5 (p = 0.007). The HR was significantly lower in the R5 group than in the R3 group at T3 (p = 0.004) and T4 (p = 0.007). The RR was significantly lower in the R5 group than in the R4 group at T4 (p = 0.049) and significantly greater in the R4 group than in the R2 group at T5 (p = 0.024) and T6 (p = 0.020). The RR was significantly lower in the R5 group than in the R1, R3 and R4 groups at T7 (p = 0.001). The RR was significantly greater in the R1 group than in the R2 and R5 groups at T8 (p = 0.001). The RR was significantly greater in the R4 group than in the R2 group at T8 (p = 0.001). SpO 2 was significantly lower in the R3 group than in the R1 group at T3 (p = 0.003) and significantly lower in the R3 group than in the R1 and R5 groups at T4 (p = 0.002), T5 (p = 0.001), T6 (p = 0.000), and T7 (p = 0.000). The MOAA/S scores were significantly lower in the R4 and R5 groups than in the R1 and R2 groups at T1 (p = 0.000), significantly lower in the R5 group than in the R1 and R3 groups at T2 (p = 0.004), and significantly lower in the R5 group than in the R1 group at T3 (p = 0.036)., Conclusion: The results indicated that doses of 5-5.5 mg remimazolam are more suitable for sedation in elderly patients, and the loss of consciousness time and depth of sedation differed according to the remimazolam dosage. Doses of 5-5.5 mg remimazolam were associated with adequate levels of sedation in elderly patients and with a decreased risk of complications, whilst haemodynamic fluctuations occurred approximately 12-15 min after the administration of remimazolam., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Modeling molecular activity and quantitative structure-activity relationships of chemical compounds is critical in drug design. Graph neural networks, which utilize molecular structures as frames, have shown success in assessing the biological activity of chemical compounds, guiding the selection and optimization of candidates for further development. However, current models often overlook activity cliffs (ACs)-cases where structurally similar molecules exhibit different bioactivities-due to latent spaces primarily optimized for structural features. Here, we introduce AC-awareness (ACA), an inductive bias designed to enhance molecular representation learning for activity modeling. The ACA jointly optimizes metric learning in the latent space and task performance in the target space, making models more sensitive to ACs. We develop ACANet, an AC-informed contrastive learning approach that can be integrated with any graph neural network. Experiments on 39 benchmark datasets demonstrate that AC-informed representations of chemical compounds consistently outperform standard models in bioactivity prediction across both regression and classification tasks. AC-informed models show strong performance in predicting pharmacokinetic and safety-relevant molecular properties. ACA paves the way toward activity-informed molecular representations, providing a valuable tool for the early stages of lead compound identification, refinement, and virtual screening., Competing Interests: Competing interests The authors declare no competing interests.

Neurodegenerative diseases (NDDs), as a neurological disorder characterised by neuronal degeneration and death, are a serious threat to human health and have long attracted attention due to their complex pathogenesis and the ineffectiveness of therapeutic drugs. Existing studies have shown that Polygonatum Sibiricum polysaccharides (PSP) have immunoregulatory, antioxidant, anti-inflammatory and other pharmacological effects, and their neuroprotective effects have been demonstrated in several scientific studies. This paper reviews the main pharmacological effects and mechanisms of PSP in the protection and treatment of NDDs, to provide a reference for the clinical application and basic research of PSP in NDDs., Competing Interests: Declaration of competing interest Since 2016, Polygonatum sibiricum polysaccharides (PSP) as one of the most important active compounds in PS have gradually become a hot research topic of the moment, which has a sweet taste, low toxicity, rich bioactivity, is more suitable for long-term administration and is widely used in cardiovascular and diabetic treatments. Recent studies have demonstrated the great potential of PSP in neuroprotective effects and its obvious role in improving behavioral deficits caused by cerebral nerve damage, but the current state of knowledge in sorting out the progress and mechanisms of its intervention in Neurodegenerative Disease (NDDs) still lacks adequate theoretical support. This study reviews the pathogenesis of NDDs, the composition, safety and bioactivity of PSP, and the interventional effects and mechanisms of PSP on NDDs to provide a research basis for the discovery and development of potential neuroprotective agents and the clinical prevention and treatment of NDDs., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Metformin is known for its antioxidant properties and ability to ameliorate metabolic dysfunction-associated fatty liver disease (MAFLD) and is the focus of this study. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is linked to MAFLD risk. This study investigated the effects of metformin on ferroptosis in free fatty acid (FFA)-treated Huh7 hepatoma cells and its association with MAFLD risk. Using Western blot, immunofluorescence, and ELISA, this study revealed that FFA treatment led to increased intracellular fat and iron accumulation, heightened Lp-PLA2 expression, reduced levels of the cysteine transporter SLC7A11 and glutathione peroxidase 4 (GPX4), altered glutathione (GSH)/oxidized glutathione (GSSG) ratios, generation of reactive oxygen species (ROS), and initiation of lipid peroxidation, which ultimately resulted in cell ferroptosis. Importantly, metformin reversed FFA-induced iron accumulation, and this effect was attenuated by ferrostatin-1 but enhanced by erastin, RSL3, and si-GPX4. Additionally, metformin activated antioxidant and antiapoptotic mechanisms, which reduced lipid peroxidation and suppressed Lp-PLA2 expression in FFA-treated Huh7 cells. In conclusion, our findings indicate that metformin may protect against MAFLD by inhibiting iron accumulation and Lp-PLA2 expression through the ROS, ferroptosis, and apoptosis signaling pathways. This study highlights potential therapeutic strategies for managing MAFLD-related risks and emphasizes the diverse roles of metformin in maintaining hepatocyte balance.

Comparative proteomics and non-target metabolomics, together with physiological and microstructural analyses of wheat grains (at 15, 20, 25, and 30 days after anthesis) from two different quality wheat varieties (Gaoyou 5766 (strong-gluten) and Zhoumai 18) were performed to illustrate the grain filling material dynamics and to search for quality control genes. The differential expressions of 1541 proteins and 406 metabolites were found. They were mostly engaged in protein metabolism, stress/defense, energy metabolism, and amino acid metabolism, and the metabolism of stored proteins and carbohydrates was the major focus of the latter stages. The core proteins and metabolites in the growth process were identified, and the candidate genes for quality differences were screened. In conclusion, this study offers a molecular explanation for the establishment of wheat quality, and it aids in our understanding of the intricate metabolic network between different qualities of wheat at the filling stage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Sewage sludge (SS) is commonly used as agricultural fertilizer worldwide. However, the toxic metal(loid)s in SS raises concerns about soil contamination and the potential risks to human health. This study, conducted since 2007 on the North China Plain, examines the impact of SS use on crops. An experiment was designed with five treatments: conventional fertilization (CK) and four levels of SS application (W1, W2, W3, and W4: 4.5, 9.0, 18.0, and 36.0 t ha -1 , respectively). Soil concentrations of eight toxic metal(loid)s (Zn, Cu, Cr, Cd, Ni, Pb, As, and Hg) were analyzed to assess pollution risk using various indices. Health risks associated with maize and wheat grains were also evaluated. Additionally, the impact of long-term SS application on crop yield, soil quality, and human health within a wheat-maize rotation system was examined. SS application increased wheat and maize yields by 5.37 to 19.08 % and 6.97 to 17.94 %, respectively, across treatments W2 to W4. Despite the toxic metal(loid)s in the grains remaining within safe limits, their concentrations showed an upward trend, especially under the W4 treatment. Moreover, SS application significantly increased the soil Zn, Cu, Cr, Cd, Pb, and Hg levels (P < 0.05) without exceeding the national standards. The geo-accumulation index values revealed rising pollution levels for Zn, Cu, Cd, and Hg, which shifted from no contamination to moderate contamination and then to moderate-to-high contamination, yet the overall pollution level remained safe. Soil ecological risks increased from moderate to serious, with Hg posing the greatest risk, particularly under the W4 treatment. Long-term crop intake from the area significantly exposed children and adults to As, contributing 42.12 % and 34.62 % to hazard index (HI), respectively. The HI values for toxic metal(loid)s in these grains surpassed one in both age groups, suggesting health risks from long-term SS cultivated crops., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

During an investigation of fungal diversity from freshwater environments in different regions in Jiangxi Province, China, four interesting species were collected. Morphology coupled with combined gene analysis of an ITS, LSU, SSU, and rpb2 DNA sequence data showed that they belong to the family Pleurotheciaceae . Four new species, Pleurotheciella ganzhouensis , Pla. irregularis , Pla. verrucosa , and Pleurothecium jiangxiense are herein described. Pleurotheciella ganzhouensis is characterized by its capsule-shaped conidia and short conidiophores, while Pla. irregularis has amorphous conidiophores and 3-septate conidia. Pleurotheciella verrucosa has cylindrical or verrucolose conidiogenous cells, 1-septate, narrowly fusiform, meniscus or subclavate conidia. Pleurothecium jiangxiense characterized in having conidiogenous cells with dense cylindrical denticles and short conidiophores. Pleurothecium obovoideum was transferred to Neomonodictys based on phylogenetic evidence. All species are compared with other similar species and comprehensive descriptions, micrographs, and phylogenetic data are provided., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 He, Zhang, Zhai, Tennakoon, Cui, Zhou, Chen, Hu, Yin, Gao, Hu and Song.)

This article comprehensively reviews how cerebral hypoxia impacts the physiological state of neurons and dendritic spines through a series of molecular changes, and explores the causal relationship between these changes and neuronal functional impairment. As a severe pathological condition, cerebral hypoxia can significantly alter the morphology and function of neurons and dendritic spines. Specifically, dendritic spines, being the critical structures for neurons to receive information, undergo changes such as a reduction in number and morphological abnormalities under hypoxic conditions. These alterations further affect synaptic function, leading to neurotransmission disorders. This article delves into the roles of molecular pathways like MAPK, AMPA receptors, NMDA receptors, and BDNF in the hypoxia-induced changes in neurons and dendritic spines, and outlines current treatment strategies. Neurons are particularly sensitive to cerebral hypoxia, with their apical dendrites being vulnerable to damage, thereby affecting cognitive function. Additionally, astrocytes and microglia play an indispensable role in protecting neuronal and synaptic structures, regulating their normal functions, and contributing to the repair process following injury. These studies not only contribute to understanding the pathogenesis of related neurological diseases but also provide important insights for developing novel therapeutic strategies. Future research should further focus on the dynamic changes in neurons and dendritic spines under hypoxic conditions and their intrinsic connections with cognitive function., (© 2024. The Author(s).)

Introduction: In Northeast China, Dorper and Australian White rams are commonly crossbred with small-tailed Han (STH) ewes to improve the offspring's meat yield and quality. However, the differences in traits and the flavor between the crossbred sheep and STH sheep remain unclear. In addition, the candidate genes potentially influencing the meat quality in the three sheep breeds require further verification., Methods: A total of 18 2-month-old healthy rams were raised over a period of 5 months, which included 6 STH, 6 Dorper and small-tailed Han crossbred (Do × STH), and 6 Australian white and small-tailed Han crossbred (Au × STH) offspring. The differences in slaughter, meat quality traits, fatty acid and amino acid composition in the muscular longissimus dorsi (MLD), and volatile compounds in the semitendinosus muscle were compared between the sheep breeds. The candidate genes related to intramuscular fat (IMF) content and fatty acids were validated., Results: The results of this study revealed that the crossbred sheep had higher body weight, carcass weight, bone weight, net meat weight, and IMF content than the STH sheep ( p < 0.05). The Do × STH offspring had a higher pH value (24 h), moisture content, and cooking percentage; they also had redder and brighter meat color. The content of myristate, palmitic, and margaric acids in the crossbred sheep was higher than that in the STH sheep ( p < 0.05). The Do × STH offspring had the highest saturated fatty acid content ( p < 0.05). The Au × STH offspring had the highest protein content ( p < 0.05). The arachidonic acid and amino acid (Asp, Ala, Ile, Leu, Lys, Thr, and essential amino acid) contents were higher in the STH sheep than in the crossbred sheep ( p < 0.05). The odor activity value (OAV) analysis showed that most of the aldehydes in the Au × STH offspring had higher values. The PDK4 gene expression was positively associated with the IMF content and was negatively correlated with the linoleic acid content in the Do × STH sheep ( p < 0.05). The TMEM273 gene expression was positively associated with linoleic and arachidonic acid contents and was negatively correlated with oleic and palmitic acid contents in the Do × STH sheep ( p < 0.05)., Discussion: The results showed the differences between the crossbred sheep and STH sheep and provided the candidate genes related to meat quality in sheep., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xiao, Liu, Zhao, Liang, Cui, Yang, Fang, Miao, Yuan, Lin, Zhai, Zhao, Zhang, Ma, Jin and Cao.)

To investigate the effects of fertilization methods and types on wheat rhizosphere microorganisms, macroelement (N, K) and microelement (Zn) fertilizers were applied on wheat by foliar spraying (FS) and root irrigation (RI) methods in a field experiment. The results indicated that fertilization methods and types can have significant impacts on the diversity and structure of rhizospheric microorganisms in wheat. The application method produced more significant effects than the fertilizer type. RI-N played a more important role in improving the wheat yield and quality and affected the changes in some nitrogen-fixing bacterial communities. Finally, eight strains of bacteria belonging to Pseudomonas azotoformans and P. cedrina showed positive effects on the growth of wheat seedlings. Overall, our study provides a better understanding of the dynamics of wheat rhizosphere microbial communities and their relation to fertilization, yield, and quality, showing that plant growth-promoting rhizobacteria with nitrogen fixing may be a potential approach for more sustainable agriculture production.

Chloroplasts are green plastids in the cytoplasm of eukaryotic algae and plants responsible for photosynthesis. The plastid-encoded RNA polymerase (PEP) plays an essential role during chloroplast biogenesis from proplastids and functions as the predominant RNA polymerase in mature chloroplasts. The PEP-centered transcription apparatus comprises a bacterial-origin PEP core and more than a dozen eukaryotic-origin PEP-associated proteins (PAPs) encoded in the nucleus. Here, we determined the cryo-EM structures of Nicotiana tabacum (tobacco) PEP-PAP apoenzyme and PEP-PAP transcription elongation complexes at near-atomic resolutions. Our data show the PEP core adopts a typical fold as bacterial RNAP. Fifteen PAPs bind at the periphery of the PEP core, facilitate assembling the PEP-PAP supercomplex, protect the complex from oxidation damage, and likely couple gene transcription with RNA processing. Our results report the high-resolution architecture of the chloroplast transcription apparatus and provide the structural basis for the mechanistic and functional study of transcription regulation in chloroplasts., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In this study, the influence of the physicochemical properties and proportioning conditions of metakaolin on the mechanical properties of the synthesized metakaolin geopolymers was comprehensively evaluated, and the issue of the reaction control mechanism for the formation of mechanical properties during the synthesis of geopolymers was addressed. The reaction mechanism was analyzed by SEM and FTIR, and the kinetic analysis of the geopolymerization process was carried out using isothermal calorimetry combined with the Jander model. The test results show that the physicochemical properties of the metakaolin and the proportioning conditions together affect the mechanical properties of the geopolymer, with the correlation between the active aluminum content of the metakaolin and the strength of the geopolymer reaching over 0.87. The early stages of the geopolymerization reaction are all controlled by nucleation-growth mechanisms ( N < 1), and the variability in control mechanisms is mainly found in the later stages of the geopolymerization reaction. The low reactivity and slow exothermic hydration of metakaolin are more inclined to the nucleation-growth mechanism responsible for the hydration process due to the large amount of encapsulation.

Antimicrobial resistance (AMR) is a major threat to global public health, and antibiotic resistance genes (ARGs) are widely distributed across humans, animals, and environment. Farming environments are emerging as a key research area for ARGs and antibiotic resistant bacteria (ARB). While the skin is an important reservoir of ARGs and ARB, transmission mechanisms between farming environments and human skin remain unclear. Previous studies confirmed that swine farm environmental exposures alter skin microbiome, but the timeline of these changes is ill defined. To improve understanding of these changes and to determine the specific time, we designed a cohort study of swine farm workers and students through collected skin and environmental samples to explore the impact of daily occupational exposure in swine farm on human skin microbiome. Results indicated that exposure to livestock-associated environments where microorganisms are richer than school environment can reshape the human skin microbiome and antibiotic resistome. Exposure of 5 h was sufficient to modify the microbiome and ARG structure in workers' skin by enriching microorganisms and ARGs. These changes were preserved once formed. Further analysis indicated that ARGs carried by host microorganisms may transfer between the environment with workers' skin and have the potential to expand to the general population using farm workers as an ARG vector. These results raised concerns about potential transmission of ARGs to the broader community. Therefore, it is necessary to take corresponding intervention measures in the production process to reduce the possibility of ARGs and ARB transmission., Competing Interests: The authors have declared no competing interests., (© 2024 The Authors. iMeta published by John Wiley & Sons Australia, Ltd on behalf of iMeta Science.)

Myocardial ischemia‒reperfusion injury is a severe cardiovascular disease, and its treatment and prevention are crucial for improving patient prognosis and reducing the economic burden. This study aimed to explore the impact of hydrogen (H 2 ) on hypoxia/reoxygenation (H/R) injury in H9c2 cells (derived from rat embryonic heart tissue) induced by hydrogen peroxide (H 2 O 2 ) and to elucidate its underlying mechanism. An H/R injury model was established in H9c2 cells via exposure to 15 μM H 2 O 2 for 3 hours, followed by incubation in a 5% CO 2 atmosphere at 37°C for 24 hours. Then, the cells were treated with H 2 (50%) for 6, 12 or 24 hours. The results demonstrated that H9c2 cells exposed to H 2 O 2 and subjected to H/R injury presented a marked decrease in the cell survival rate, accompanied by severe morphological alterations, such as curling and wrinkling, and elevated lactate dehydrogenase levels. Notably, H 2 mitigated H/R injury induced by H 2 O 2 in a time-dependent manner, improving the morphological damage observed in H9c2 cells and decreasing lactate dehydrogenase levels. Compared with the model group, treatment with H 2 increased the activities of antioxidant enzymes, including catalase, superoxide dismutase, and glutathione peroxidase, while concurrently reducing the level of malondialdehyde, an indicator of cellular damage. Furthermore, H 2 treatment downregulated the expression of inflammatory cytokines and inflammatory-related factors, specifically interleukin-6, high-mobility group box 1, tumor necrosis factor-alpha, and Toll-like receptor 4, in H9c2 cells post-H/R injury. Furthermore, H 2 treatment resulted in a marked decrease in the expression levels of proteins associated with the Wnt/C-X3-C-motif receptor 1 signaling pathway, such as β-catenin, glycogen synthase kinase-3 beta, adenomatous polyposis coli, and Wnt and C-X3-C-motif receptor 1. This observation suggests a potential mechanism for its protective effects against H/R injury. Therefore, H 2 exerts a protective effect against H/R injury in H9c2 cells induced by H 2 O 2 , potentially by inhibiting the activated Wnt/C-X3-C-motif receptor 1 signaling pathway. This inhibition, in turn, prevents the generation of oxidative stress, inflammatory cytokines, and inflammation-associated factors., (Copyright © 2025 Medical Gas Research.)

Arthritis is a group of diseases characterized by joint pain, swelling, stiffness, and limited movement. Osteoarthritis, rheumatoid arthritis, and gouty arthritis are the most common types of arthritis. Arthritis severely affects the quality of life of patients and imposes a heavy financial and medical burden on their families and society at large. As a widely used traditional Chinese medicine, Herba siegesbeckiae has many pharmacological effects such as anti-inflammatory and analgesic, anti-ischemic injury, cardiovascular protection, and hypoglycemic. In addition, it has significant therapeutic effects on arthritis. The rich chemical compositions of H. siegesbeckiae primarily include diterpenoids, sesquiterpenoids, and flavonoids. As one of the main active components of H. siegesbeckiae, kirenol and quercetin play a vital role in reducing arthritis symptoms. In the present study, the research progress in arthritis treatment with the active components of H. siegesbeckiae is reviewed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Purpose: To investigate the inhibitory effect of paeoniflorin(PF) with different concentrations on CAL27 cells of tongue squamous cell carcinoma in vitro and its possible mechanism., Methods: CCK-8 technique and clone formation trial were used to detect the effect of PF on the proliferation and clone formation of CAL27 cells. Scratch test and Transwell method was used to detect the effects of PF on migration and invasion of CAL27 cells. Staining of Hoechst33342 was employed to evaluate the influence of PF on apoptosis of CAL27 cells, while Western blot was utilized to investigate the effect of PF on the expression of NF-κB pathway related proteins and EMT related proteins. The effect of PF on NO production in CAL27 cells was detected by nitric oxide detection kit. Statistical analysis was performed with SPSS 27.0 software package., Results: PF inhibited proliferation, migration, and invasion of CAL27 cells in vitro in a concentration-dependent way. Moreover, PF caused apoptosis of CAL27 cells. PF impeded NF-κB pathway activity, decreased the expression of P-P65, further reduced the expression of iNOS and MMP-9, suppressed the production of NO, and concurrently inhibited Vimentin,promoted E-cadherin., Conclusions: Paeoniflorin inhibits the proliferation, migration and invasion of CAL27 cells, which may play an anti-cancer role by inhibiting the activation of NF-κB pathway and EMT.

Heat stress is a major abiotic stress that can cause serious losses of a crop. Our previous work identified a gene involved in heat stress tolerance in wheat, TaPLC1-2B . To further investigate its mechanisms, in the present study, TaPLC1-2B RNAi-silenced transgenic wheat and the wild type were comparatively analyzed at both the seedling and adult stages, with or without heat stress, using transcriptome sequencing. A total of 15,549 differentially expressed genes (DEGs) were identified at the adult stage and 20,535 DEGs were detected at the seedling stage. After heat stress, an enrichment of pathways such as phytohormones and mitogen-activated protein kinase signaling was mainly found in the seedling stage, and pathways related to metabolism, glycerophospholipid metabolism, circadian rhythms, and ABC transporter were enriched in the adult stage. Auxin and abscisic acid were downregulated in the seedling stage and vice versa in the adult stage; and the MYB , WRKY , and no apical meristem gene families were downregulated in the seedling stage in response to heat stress and upregulated in the adult stage in response to heat stress. This study deepens our understanding of the mechanisms of TaPLC1-2B in regard to heat stress in wheat at the seedling and adult stages.

Developing a high-efficiency photoelectrochemical (PEC) electrode for the glycerol oxidation reaction (GOR) is important for producing valuable products. The PEC performance could be enhanced by rationally designing heterostructures with inhibited recombination of charge carriers. Nevertheless, the interface electronic structure of heterostructures has not been comprehensively analyzed. In this work, the PEC GOR performance of ZnIn 2 S 4 /TiO 2 heterostructure photoanode showed 1.7 folds enhancement than that of pure TiO 2 photoanode at 1.23 V vs. RHE. The ZnIn 2 S 4 /TiO 2 heterostructure was simulated by constructing ZnIn 2 S 4 on the TiO 2 single crystal, which was beneficial for investigating the interface electronic structure of heterostructure. Single-particle spectroscopy demonstrated a significantly increased lifetime of charge carriers. Combined with the in-situ X-ray photoelectron spectroscopy, Kelvin probe force microscopy, work function, and electron paramagnetic resonance, the interface electronic structure of the ZnIn 2 S 4 /TiO 2 heterostructure was proposed with a Z-scheme mechanism. This work provides a comprehensive strategy for analyzing the interface electronic structure of heterostructures., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Nitroxide (NO) spin radicals are effective in characterizing structures, interactions and dynamics of biomolecules. The EPR applications in cell lysates or intracellular milieu require stable spin labels, but NO radicals are unstable in such conditions. We showed that the destabilization of NO radicals in cell lysates or even in cells is caused by NADPH/NADH related enzymes, but not by the commonly believed reducing reagents such as GSH. Maleimide stabilizes the NO radicals in the cell lysates by consumption of the NADPH/NADH that are essential for the enzymes involved in destabilizing NO radicals, instead of serving as the solo thiol scavenger. The maleimide treatment retains the crowding properties of the intracellular components and allows to perform long-time EPR measurements of NO labeled biomolecules close to the intracellular conditions. The strategy of maleimide treatment on cell lysates for the EPR applications has been demonstrated on double electron-electron resonance (DEER) measurements on a number of NO labeled protein samples. The method opens a broad application range for the NO labeled biomolecules by EPR in conditions that resemble the intracellular milieu., (© 2023 Wiley-VCH GmbH.)

Visualization and quantification of important biomolecules like glutathione (GSH) in live cells are highly important. The existing methods are mostly from optical detection and lack of atomic resolution on the activity of GSH. Here, we present a sensitive 19 F-NMR method to quantify real-time variations of GSH in live cells in a reversible manner. This NMR method prevents extracellular leakage and irreversible consumption of intracellular GSH during the detection. The high performance of the reactive 19 F-probe enables accurate determination of intracellular GSH content at atomic resolution, from which information on GSH variations with respect to the extracellular and intracellular conditions can be inferred. In addition, we demonstrate the applicability of this NMR method to quantify the GSH levels between different live cell lines and to disclose the distinct differences between the intracellular environment and cell lysates. We foresee the application of 19 F-NMR to monitor real-time variations of intracellular GSH levels in relation to GSH-involved central cellular processes., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Antimicrobial photodynamic therapy (aPDT) is a non-pharmacological antimicrobial regimen based on light, photosensitizer and oxygen. It has become a potential method to inactivate multidrug-resistant bacteria. However, limited by the delivery of photosensitizer (PS) in biofilm, eradicating biofilm-associated infections by aPDT remains challenging. This study aimed to explore the feasibility of combining ultrasonic irradiation with aPDT to enhance the efficacy of aPDT against methicillin-resistant staphylococcus aureus (MRSA) biofilm. A cationic benzylidene cyclopentanone photosensitizer with much higher selectivity to bacterial cells than mammalian cells were applied at the concentration of 10 μM. 532 nm laser (40 mW/cm 2 , 10 min) and 1 MHz ultrasound (500 mW/cm 2 , 10 min, simultaneously with aPDT) were employed against MRSA biofilms in vitro. In addition to combined with ultrasonic irradiation and aPDT, MRSA biofilms were treated with laser irradiation only, photosensitizer only, ultrasonic irradiation only, ultrasonic irradiation and photosensitizer, and aPDT respectively. The antibacterial efficacy was determined by XTT assay, and the penetration depth of PS in biofilm was observed using a photoluminescence spectrometer and a confocal laser scanning microscopy (CLSM). In addition, the viability of human dermal fibroblasts (WS-1 cells) after the same treatments mentioned above and the uptake of P3 by WS-1 cells after ultrasonic irradiation were detected by CCK-8 and CLSM in vitro. Results showed that the percent decrease in metabolic activity resulting from the US + aPDT group (75.76%) was higher than the sum of the aPDT group (44.14%) and the US group (9.88%), suggesting synergistic effects. Meanwhile, the diffusion of PS in the biofilm of MRSA was significantly increased by 1 MHz ultrasonic irradiation. Ultrasonic irradiation neither induced the PS uptake by WS-1 cells nor reduced the viability of WS-1 cells. These results suggested that 1 MHz ultrasonic irradiation significantly enhanced the efficacy of aPDT against MRSA biofilm by increasing the penetration depth of PS. In addition, the antibacterial efficacy of aPDT can be enhanced by ultrasonic irradiation, the US + aPDT treatment demonstrated encouraging in vivo antibacterial efficacy (1.73 log 10 CFU/mL reduction). In conclusion, the combination of aPDT and 1 MHz ultrasound is a potential and promising strategy to eradicate biofilm-associated infections of MRSA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Competing Interests: Conflicts of interest: All authors have disclosed no conflicts of interest.

Drought and salt stress are important factors that affect plant growth and development and cause crop yield reductions worldwide. Phospholipase C is a class of enzymes that can hydrolyze phospholipids, and it has been shown to play an important role in plant growth regulation and stress response. We used rice as a model to investigate the function of the wheat TaPI-PLC1-2B gene in salt and drought tolerance. For this purpose, we heterologously expressed the TaPI-PLC1-2B gene in rice and studied the transcriptional differences in transgenic and wide-type rice plants in the presence and absence of drought and salt stress. Our results showed that 2130 and 1759 genes expressed differentially in the TaPI-PLC1-2B overexpression rice line under salt and drought stress, respectively. Gene ontology enrichment results showed that differentially expressed genes (DEGs) were significantly enriched in cellular process, metabolic process, stimulus-response, cell, organelle, catalytic activity, and other functional processes under salt and drought stress. In addition, the Kyoto Encyclopedia of Genes and Genomes pathway analysis showed DEG enrichment in plant-pathogen interaction, phosphoinositol, plant hormones, and other signaling pathways under the two stress treatments. Furthermore, the chromosomal localization of salt and drought stress-responsive DEGs showed a clear distribution pattern on specific rice chromosomes. For instance, the greatest number of drought stress-responsive genes mapped to rice chromosomes 1 and 6. The current analysis has built the basis for future explorations to decipher the TaPI-PLC1-2B-mediated plant stress response mechanism in the relatively challenging wheat system., (© 2022. The Author(s), under exclusive licence to The Genetics Society.)

Background: The turnover time of positive blood culture using traditional methods takes too long. This study aimed to evaluate rapid direct identification and drug sensitivity test methods for pathogens in positive blood cultures., Methods: A total of 403 blood culture bottles were used to compare the rapid identification methods and drug sensitivity tests for pathogens causing bloodstream infections. Bacteria were enriched using separator gel tubes and were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. In addition, bacteria were also identified using an established traditional method for comparison. The sensitivity of gram-negative bacilli against antibiotics was tested using Rapid Bacterial Test Strips or the VITEK 2 Compact system., Results: The accuracy was 81.8% in 403 bacteria, of which 71% (132/186) and 96.3% (209/217) were gram-positive and gram-negative bacteria, respectively. The gram-positive bacteria were primarily Staphylococcus aureus and coagulase-negative Staphylococcus. The gram-negative bacteria were primarily Escherichia coli and Klebsiella pneumonia. Compared with routine drug sensitivity testing methods, the coincidence rate of direct drug sensitivity testing for classifying the bacteria was 98.6% (1,325/1,344). The average rapid bacterial identification time was 1.5 hours, and the direct drug sensitivity test took - 8.5 hours., Conclusions: The present study showed that direct identification and rapid drug sensitivity testing can be performed on the same day and can be completed 1 or 2 days ahead of routine methods, thereby assisting in providing earlier drug options for anti-infective therapy.

Flag leaf senescence is an important determinant of wheat yield, as leaf senescence occurs in a coordinated manner during grain filling. However, the biological process of early senescence of flag leaves post-anthesis is not clear. In this study, early senescence in wheat was investigated using a high-throughput RNA sequencing technique. A total of 4887 differentially expressed genes (DEGs) were identified, and any showing drastic expression changes were then linked to particular biological processes. A hierarchical cluster analysis implied potential relationships between NAC genes and post-anthesis senescence in the flag leaf. In addition, a large set of genes associated with the synthesis; transport; and signaling of multiple phytohormones (JA, ABA, IAA, ET, SA, BR, and CTK) were expressed differentially, and many DEGs related to ABA and IAA were identified. Our results provide insight into the molecular processes taking place during the early senescence of flag leaves, which may provide useful information in improving wheat yield in the future.

The rapid dissemination of plasmid-mediated tet (X) genes in Acinetobacter species has compromised the clinical effectiveness of tigecycline, one of the last-resort antibiotics. However, the classification strategy and homology group of tet (X)-positive Acinetobacter spp. plasmids remain largely unknown. In this study, we classified them by genome-based replicon typing, followed by analyses of structural characteristics, transferability and in vivo effect. A total of 34 plasmids distributed in at least nine Acinetobacter species were collected, including three tet (X3)-positive plasmids and one tet (X6)-positive plasmid from our genome sequencing results. Among them, there were 28 plasmids carrying Rep&#95;3 superfamily replicase genes and classified into six homology groups, consisting of GR31 (82.1%), GR26 (3.6%), GR41 (3.6%), GR59 (3.6%), and novel groups GR60 (3.6%) and GR61 (3.6%). Our tet (X3)-positive plasmids pYH16040-1, pYH16056-1, and pYH12068-1 belonged to the dominant GR31 group, whereas the tet (X6)-positive plasmid pYH12068-2 was unclassified. Structurally, all tet (X)-positive GR31 plasmids shared similar plasmid replication ( repB ), stability ( parA and parB ) and accessory modules [ tet (X) and sul2 ], and 97.6% of plasmid-mediated tet (X) genes in Acinetobacter species were adjacent to IS CR2 . Conjugation and susceptibility testing revealed pYH16040-1, pYH16056-1, and pYH12068-2, carrying plasmid transfer modules, were able to mediate the mobilization of multiple antibiotic resistance. Under the treatment of tigecycline, the mortality rate of Galleria mellonella infected by pYH16040-1-mediated tet (X3)-positive Acinetobacter spp. isolate significantly increased when compared with its plasmid-cured strain ( p < 0.0001). The spread of such plasmids is of great clinical concern, more effects are needed and will facilitate the future analysis of tet (X)-positive Acinetobacter spp. plasmids., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Huang, Cui, He, Sun, Liu and Huang.)

Heterogeneous peroxymonosulfate (PMS)-based advanced oxidation processes (AOPs) have shown a great potential for pollutant degradation, but their feasibility for large-scale water treatment application has not been demonstrated. Herein, we develop a facile coprecipitation method for the scalable production (∼10 kg) of the Cu-Fe-Mn spinel oxide (CuFeMnO). Such a catalyst has rich oxygen vacancies and symmetry-breaking sites, which endorse it with a superior PMS-catalytic capacity. We find that the working reactive species and their contributions are highly dependent on the properties of target organic pollutants. For the organics with electron-donating group (e.g., -OH), high-valent metal species are mainly responsible for the pollutant degradation, whereas for the organics with electron-withdrawing group (e.g., -COOH and -NO 2 ), hydroxyl radical (•OH) as the secondary oxidant also plays an important role. We demonstrate that the CuFeMnO-PMS system is able to achieve efficient and stable removal of the pollutants in the secondary effluent from a municipal wastewater plant at both bench and pilot scales. Moreover, we explore the application prospect of this PMS-based AOP process for large-scale wastewater treatment. This work describes an opportunity to scalably prepare robust spinel oxide catalysts for water purification and is beneficial to the practical applications of the heterogeneous PMS-AOPs.

Objective: To explore the application value of nurse stratified management in nursing management., Methods: One hundred nurses who worked in our hospital from June 2019 to September 2021 were recruited and assigned via the random number table method to an observation group ( n  = 50) and the control group ( n  = 50). The control group received routine nursing management, and the experimental group received stratified nursing management. The nursing quality, practice happiness, error rate, patient complaint, and patient satisfaction were compared between the two groups., Results: The experimental group showed a significantly higher nursing quality than the control group ( P < 0.05). The experimental group had significantly higher practice happiness among nurses than the control group ( P < 0.05). Stratified nursing management mode resulted in a significantly lower error rate and patient complaint versus routine nursing management mode ( P < 0.05). Patients were more satisfied with stratified nursing management than with the routine nursing management ( P < 0.05)., Conclusion: The nurse stratified management method effectively improves the nursing quality and practice happiness of nurses, reduces the error rate of nursing and patient complaint, and increases nursing satisfaction., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Qing Liu et al.)

The Licha black pig, a popular indigenous Chinese pig breed, is known for its multi-vertebral trait and higher lean meat rate. Understanding the current conservation status, family structure, and degree of inbreeding of the Licha black pig population will be useful to maintain a sufficient level of genetic diversity in these animal resources. In the present study, the genetic diversity, population structure, and inbreeding coefficient of this conserved population were analyzed using SNP genotyping data from 209 Licha black pigs. Based on the genomic information, this population was divided into eight different families with boars. The effective population size (N e ), polymorphic marker ratio (P N ), expected heterozygosity (H e ), and observed heterozygosity (H o ) of this population were 8.7, 0.827, 0.3576, and 0.3512, respectively. In addition, a total of 5976 runs of homozygosity (ROHs) were identified, and most of the ROHs (54.9%) were greater than 5 Mb. The genomic inbreeding coefficient of each individual was estimated based on ROHs ( F ROH ) with an average inbreeding coefficient of 0.11 for the population. Five statistics (N e , P N , H o , H e , and F ROH ) showed a decrease in the level of genetic diversity and a high degree of inbreeding in this population. Thus, special preservation programs need to be implemented in the future, such as introducing new individuals or improving the mating plan. Altogether, our study provides the first genomic overview of the genetic diversity and population structure of Licha black pigs, which will be useful for the management and long-term preservation of this breed.

The emergence of novel plasmid-mediated high-level tigecycline resistance genes tet(X) in the Enterobacteriaceae has increased public health risk for treating severe bacterial infections. Despite growing reports of tet(X)-positive isolates detected in animal sources, the epidemiological association of animal- and environment-derived isolates with human-derived isolates remains unclear. Here, we performed a comprehensive analysis of tet(X4)-positive Escherichia coli isolates collected in a hospital in Guangdong province, China. A total of 48 tet(X4)-positive E. coli isolates were obtained from 1001 fecal samples. The tet(X4)-positive E. coli isolates were genetically diverse but certain strains that belonged to ST48, ST10, and ST877 etc. also have clonally transmitted. Most of the tet(X4) genes from these patient isolates were located on conjugative plasmids that were successfully transferred (64.6%) and generally coexisted with other antibiotic resistance genes including aadA, floR, bla TEM and qnrS. More importantly, we found the IncX1 type plasmid was a common vector for tet(X4) and was prevalent in these patient-derived strains (31.3%). This plasmid type has been detected in animal-derived strains from different species in different regions demonstrating its strong transmission ability and wide host range. Furthermore, phylogenetic analysis revealed that certain strains of patient and animal origin were closely related indicating that the tet(X4)-positive E. coli isolates were likely to have cross-sectorial clonal transmission between humans, animals, and farm environments. Our research greatly expands the limited epidemiological knowledge of tet(X4)-positive strains in clinical settings and provides definitive evidence for the epidemiological link between human-derived tet(X4)-positive isolates and animal-derived isolates., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)

Anaerobic digestion (AD) with hydrothermal (HT) pretreatment (sequential HT-AD treatment) is a novel technology for sludge management. HT-AD sludge is rich in functional groups and its applications as pollutant sorbents might be a win-win strategy. This study investigated the removal of uranium (VI) from water using HT-AD sludge as affected by solution pH, temperature, and ion strength. The reusability and heavy metal risk of HT-AD sludge were also assessed. The batch sorption experiments demonstrated that even at an acidic initial pH of 3.2, the maximum adsorption of HT-AD sludge for uranium (VI) reached 117.13 mg/g, higher than that of most carbon-based materials. The inner-sphere and out-sphere complexation between uranium (VI) and the HT-AD sludge dominated the adsorption when pH was in the range of 2-6 and 6-11, respectively. The FTIR and XPS analysis indicated that the primary mechanisms of uranium (VI) adsorption by the HT-AD sludge were the surface complexation and the electric attraction between uranium (VI) and the functional groups (e.g. -COO-) on HT-AD sludge. The removal rate of uranium (VI) by HT-AD sludge only decreased by ∼7% after 3 consecutive adsorption cycles. Leaching experiment showed that less than 5% of the total heavy metal were released from HT-AD sludge. Our research proved that HT-AD sludge can be used as an efficient uranium (VI) adsorbent with good reusability and environmental safety., (Copyright © 2021. Published by Elsevier Ltd.)

GSH, Cys, Hcy, and H 2 S are important biothiols and play important roles in the living systems. Quantitative and simultaneous determination of these biothiols under physiological conditions is still a challenge. Herein, we developed an effective 19 F-reactive tag that readily interacts with these four biothiols for the generation of stable thioether products that have distinguishable 19 F-chemical shifts. These thioester compounds encode the characteristic fingerprint profiles of each biothiols, allowing one to simultaneously quantify and determine these biothiols by 1D 19 F NMR spectroscopy. The intra-/extracellular GSH in live cells was assessed by the established strategy, and remarkable variations in the GSH stability were determined between the normal mammalian cells and cancer cells. It is notable that GSH hydrolyzes efficiently in the out-membrane of the cancer cells and the lysates. In contrast, GSH remains stable in the tested normal cells.

Tetracycline and its derivative tigecycline are clinical options against Gram-negative bacterial infections. The emergence of mobile Tet(X) enzymes that destruct tetracycline-type antibiotics is posing a big challenge to antibacterial therapy and food/environmental securities. Here, we present an update on a growing number of Tet(X) variants. We describe structure and action of Tet(X) enzyme, and discuss the evolutional origin. In addition, potential Tet(X) inhibitors are given. This mini-review might benefit better understanding of Tet(X)-mediated tigecycline resistance. This article is categorized under: Infectious Diseases > Genetics/Genomics/Epigenetics Infectious Diseases > Environmental Factors Infectious Diseases > Molecular and Cellular Physiology., (© 2021 Wiley Periodicals LLC.)

Cellular senescence, a process that arrests the cell cycle, is a cellular response mechanism for various stresses and is implicated in aging and various age-related diseases. However, the understanding of senescence in living organisms is insufficient, largely due to the scarcity of sensitive tools for the detection of cellular senescence in vivo . Herein, we describe the development of a self-immobilizing near-infrared (NIR) fluorogenic probe that can be activated by senescence-associated β - galactosidase (SA-β - Gal), the most widely used senescence marker. The NIR signal is turned on only in the presence of SA-β - Gal, and the fluorescence signal is retained to the site of activation via in situ labeling, significantly enhancing the sensitivity of the probe. We demonstrate its efficient noninvasive imaging of senescence in mice xenograft models.

The emergence of tet (X) genes has compromised the clinical use of the last-line antibiotic tigecycline. We identified 322 (1.21%) tet (X) positive samples from 12,829 human microbiome samples distributed in four continents (Asia, Europe, North America, and South America) using retrospective data from worldwide. These tet (X) genes were dominated by tet (X2)-like orthologs but we also identified 12 samples carrying novel tet (X) genes, designed tet (X45), tet (X46), and tet (X47), were resistant to tigecycline. The metagenomic analysis indicated these tet (X) genes distributed in anaerobes dominated by Bacteroidaceae (78.89%) of human-gut origin. Two mobile elements IS Bf11 and IS 4351 were most likely to promote the transmission of these tet (X2)-like orthologs between Bacteroidaceae and Riemerella anatipestifer. tet (X2)-like orthologs was also developed during transmission by mutation to high-level tigecycline resistant genes tet (X45), tet (X46), and tet (X47). Further tracing these tet (X) in single bacterial isolate from public repository indicated tet (X) genes were present as early as 1960s in R. anatipestifer that was the primary tet (X) carrier at early stage (before 2000). The tet (X2) and non- tet (X2) orthologs were primarily distributed in humans and food animals respectively, and non- tet (X2) were dominated by tet (X3) and tet (X4). Genomic comparison indicated these tet (X) genes were likely to be generated during tet (X) transmission between Flavobacteriaceae and E. coli/Acinetobacter spp., and IS CR2 played a key role in the transmission. These results suggest R. anatipestifer was the potential ancestral source of tet (X). In addition, Bacteroidaceae of human-gut origin was an important hidden reservoir and mutational incubator for the mobile tet (X) genes that enabled spread to facultative anaerobes and aerobes. IMPORTANCE The emergence of the tigecycline resistance gene tet (X) has posed a severe threat to public health. However, reports of its origin and distribution in human remain rare. Here, we explore the origin and distribution of tet (X) from large-scale metagenomic data of human-gut origin and public repository. This study revealed the emergency of tet (X) gene in 1960s, which has refreshed a previous standpoint that the earliest presence of tet (X) was in 1980s. The metagenomic analysis from data mining covered the unculturable bacteria, which has overcome the traditional bacteria isolating and purificating technologies, and the analysis indicated that the Bacteroidaceae of human-gut origin was an important hidden reservoir for tet (X) that enabled spread to facultative anaerobes and aerobes. The continuous monitoring of mobile tigecycline resistance determinants from both culturable and unculturable microorganisms is imperative for understanding and tackling the dissemination of tet (X) genes in both the health care and agricultural sectors.

Tetracycline antibiotics (TCs) are massively produced and consumed in various industries resulting in large quantities of residuals in the environment. In this study, to achieve safe and efficient removal of residual TCs, a Pichia pastoris (P. pastoris) was gained to stably express glycosylated TCs degrading enzyme Tet(X) followed codon and expression parameter optimization of tet(X4). As expected, glycosylated Tet(X) still maintains efficient capacity of degrading TCs. The expressed Tet(X) maintained efficient TCs degrading ability over a pH range of 6.5 - 9.5 and temperature range of 17 - 47 °C. We tested this recombinant protein for its ability to degrade tetracycline in pond water and sewage models of tetracycline removal at starting levels of 10 mg/L substrate. 80.5 ± 3.8% and 26.2 ± 2.6% of tetracycline was degraded within 15 min in the presence of 0.2 μM Tet(X) and 50 μM NADPH, respectively. More importantly, the direct use of a Tet(X) degrading enzymes reduces the risk of gene transmission during degradation. Thus, the Tet(X) degrading enzyme expressed by P. pastoris is an effective and safe method for treating intractable TCs residues., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A robust method to identify and quantify amino acids close to physiological conditions by 1D 19 F NMR was established. Each 19 F-derivatized amino acid has its characteristic chemical-shift profile that is readily identified in the mixture of amino acids or in biofluids including fetal bovine serum and cell lysates. The method shows great potential in metabolomics and biochemical analysis.

Site specific installation of a paramagnetic ion with magnetic anisotropy in a biomolecule generates valuable structural restraints, such as pseudocontact shifts (PCSs) and residual dipolar couplings (RDCs). These paramagnetic effects can be used to characterize the structures, interactions and dynamics of biological macromolecules and their complexes. Two single-armed DOTA-like tags, BrPSPy-DO3M(S)A-Ln and BrPSPy-6M-DO3M(S)A-Ln, each containing a thiol-specific reacting group, that is, a phenylsulfonyl pyridine moiety, are demonstrated as rigid, reactive and stable paramagnetic tags for protein modification by formation of a reducing resistant thioether bond between the protein and the tag. The two tags present high reactivity with the solvent exposed thiol group in aqueous solution at room temperature. The introduction of Br at the meta-position in pyridine enhances the reactivity of 4-phenylsulfonyl pyridine towards the solvent exposed thiol group in a protein, whereas the ortho-methyl group in pyridine increases the rigidity of the tag in the protein conjugates. The high performance of these two tags has been demonstrated in different cysteine mutants of ubiquitin and GB1. The high reactivity and rigidity of these two tags can be added in the toolbox of paramagnetic tags suitable for the high-resolution NMR measurements of biological macromolecules and their complexes., (© 2021 Wiley-VCH GmbH.)

Objectives: Carbapenems, colistin, and tigecycline are critically important antibiotics in clinics. After the global appearance of bla NDM and mcr mediating the resistance to carbapenems and colistin, respectively, tigecycline becomes the last-resort drug against severe human infections caused by multidrug-resistant bacteria. Recently, a mobile tigecycline resistance gene tet (X4) has been identified in Escherichia coli , Klebsiella pneumoniae , and Acinetobacter baumannii that causes high resistance to tigecycline and other tetracyclines. In this study, the prevalence of tet (X4) in E. coli isolates from duck and goose farms in Southeast China was identified and characterized., Methods: Feces, soil, sewage, and dust samples were collected from duck and goose farms along with the southeast coast provinces of China. Antimicrobial susceptibility testing and polymerase chain reaction screening were performed to investigate the phenotype and genotype of tigecycline resistance. Conjugation, S1 pulsed-field gel electrophoresis (PFGE), and whole-genome sequencing were used to determine the transferability, genetic location, and the genomic characteristics of tet (X4)., Results: In total, 1,716 samples were collected, and 16 isolates (0.9%) recovered from Guangdong, Shandong, and Jiangsu were positive for tet (X4) gene with tigecycline minimum inhibitory concentrations ≥16 mg/L. Notably, among these tet (X4)-positive E. coil isolates, seven of them were from the environment samples (soil and sewage). PFGE and multilocus sequence typing demonstrated that ST3997 was the most prevalent sequence type (eight isolates, 50%) in Jiangsu province. By conjugation assays, 11 isolates were able to transfer tet (X4) plasmid to E. coli C600 recipient, and these plasmids belonged to IncHI1 and IncX1 detected by sequence analysis. tet (X4) was found adjacent to an insertion sequence IS CR2 downstream and a cat D gene upstream for all isolates. In addition, multiple-drug resistance to tigecycline, chlortetracycline, ampicillin, florfenicol, ciprofloxacin, gentamicin, trimethoprim/sulfamethoxazole, and fosfomycin was profiled in most of the tet (X4)-positive isolates., Conclusion: The identification of tet (X4) harboring E. coli strains in duck farms and their surrounding environment enlarges our knowledge of the variety and prevalence of tigecycline resistance. The prevalence of tet (X4) raises concern for the use of tetracyclines in animal farming, and the tet (X4) gene should be listed as primary gene for resistance surveillance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yu, Cui, Kuang, Chen, Wang, Liao, Sun and Liu.)

In this study, we reported the occurrence of eight organophosphorus pesticides (OPPs) in the East China Sea. Forty samples were collected and analysed with a high volume solid phase extraction method (Hi-throat/Hi-volume SPE) in the early summer of 2020. All the target OPPs were detected in the surface water at one or more stations in the East China Sea, and the concentrations of ΣOPPs were in the range 0.0775-3.09 ng/L (mean: 0.862 ± 0.624 ng/L). Terbufos sulfone and fenthion were the main pollutants in this area, probably resulting from pesticide use in China and other countries. The off-shore input from coastal regions was suggested to be a major source of OPP pollution in the East China Sea, and the movement of ocean currents played an important role in their transportation because around 0.86 t OPPs passed through the Tsushima Strait from the East China Sea each month. An ecological risk assessment showed that these OPPs presented a high risk to species in the East China Sea, whereas they posed no health risk to humans under both the median and high exposure scenario., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The emergence of the plasmid-mediated high-level tigecycline resistance mechanism Tet(X) threatens the role of tigecycline as the "last-resort" antibiotic in the treatment of infections caused by carbapenem-resistant Gram-negative bacteria. Compared with that of the prototypical Tet(X), the enzymatic activities of Tet(X3) and Tet(X4) were significantly enhanced, correlating with high-level tigecycline resistance, but the underlying mechanisms remain unclear. In this study, we probed the key amino acid changes leading to the enhancement of Tet(X) function and clarified the structural characteristics and evolutionary path of Tet(X) based upon the key residue changes. Through domain exchange and site-directed mutagenesis experiments, we successfully identified five candidate residues mutations (L282S, A339T, D340N, V350I, and K351E), involved in Tet(X2) activity enhancement. Importantly, these 5 residue changes were 100% conserved among all reported high-activity Tet(X) orthologs, Tet(X3) to Tet(X7), suggesting the important role of these residue changes in the molecular evolution of Tet(X). Structural analysis suggested that the mutant residues did not directly participate in the substrate and flavin adenine dinucleotide (FAD) recognition or binding, but indirectly altered the conformational dynamics of the enzyme through the interaction with adjacent residues. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and UV full-wavelength scanning experiments confirmed that each mutation led to an increase in activity without changing the biochemical properties of the Tet(X) enzyme. Further phylogenetic analysis suggested that Riemerella anatipestifer served as an important incubator and a main bridge vector for the resistance enhancement and spread of Tet(X). This study expands the knowledge of the structure and function of Tet(X) and provides insights into the evolutionary relationship between Tet(X) orthologs. IMPORTANCE The newly emerged tigecycline-inactivating enzymes Tet(X3) and Tet(X4), which are associated with high-level tigecycline resistance, demonstrated significantly higher activities in comparison to that of the prototypical Tet(X) enzyme, threatening the clinical efficacy of tigecycline as a last-resort antibiotic to treat multidrug-resistant (MDR) Gram-negative bacterial infections. However, the molecular mechanisms leading to high-level tigecycline resistance remain elusive. Here, we identified 5 key residue changes that lead to enhanced Tet(X) activity through domain swapping and site-directed mutagenesis. Instead of direct involvement with substrate binding or catalysis, these residue changes indirectly alter the conformational dynamics and allosterically affect enzyme activities. These findings further broaden the understanding of the structural characteristics and functional evolution of Tet(X) and provide a basis for the subsequent screening of specific inhibitors and the development of novel tetracycline antibiotics., (Copyright © 2021 Cui et al.)

Phenylethynyl-terminated aromatic polyimides meet requirements of resin transfer molding (RTM) and exhibits high glass transition temperature (T g ) were prepared. Moreover, the relationship between the polyimide backbones structure and their melting stability was investigated. The phenylethynyl-terminated polyimides were based on 4,4'-(hexafluorosiopropylidene)-diphthalic anhydride (6FDA) and different diamines of 3,4'-oxydianiline (3,4'-ODA), m-phenylenediamine (m-PDA) and 2,2'-bis(trifluoromethyl)benzidine (TFDB) were prepared. These oligoimides exhibit excellent melting flowability with wide processing temperature window and low minimum melt viscosities (<1 Pa·s). Two of the oligoimides display good melting stability at 280-290 °C, which meet the requirements of resin transfer molding (RTM) process. After thermally cured, all resins show high glass transition temperatures (T g s, 363-391 °C) and good tensile strength (51-66 MPa). The cure kinetics studied by the differential scanning calorimetry (DSC), 13 C nuclear magnetic resonance ( 13 C NMR) characterization and density functional theory (DFT) definitely confirmed that the electron-withdrawing ability of oligoimide backbone can tremendously affect the curing reactivity of terminated phenylethynyl groups. The replacement of 3,4'-ODA units by m-PDA or TFDB units increase the electron-withdrawing ability of the backbone, which increase the curing rate of terminated phenylethynyl groups at processing temperatures, hence results in the worse melting stability.

The recent emergence of plasmid-mediated tigecycline resistance gene tet(X) has challenged the clinical effectiveness of tigecycline as a last-resort treatment option. During 2017-2018, 336 fecal samples from sick ducks, pigs, chickens and geese in Guangdong, China, were screened for tet(X)-positive Acinetobacter baumannii strains. Their activities on tetracyclines were determined by microbiological degradation and mass spectrometry, followed by susceptibility testing, sequence typing, gene transfer, molecular location and genomic DNA sequencing analyses. A total of 10 tet(X)-positive A. baumannii strains were isolated from ducks and chickens, including eight plasmid-borne tet(X5)-positive and two chromosomal tet(X6)-positive isolates. All of them exhibited good degradation activities on tetracyclines by hydroxylation at C11a and were multidrug-resistant to tigecycline, tetracycline, florfenicol, ciprofloxacin and trimethoprim/sulfamethoxazole. Genetically, they belonged to two sequence types (ST355, n = 8; ST1980, n = 2) that were consistent with their pulsotypes, revealing a clonal spread of ST355 A. baumannii. An ISCR2- or IS26-mediated tet(X) transposition structure, homologous to those of clinical A. baumannii strains, was also identified and ISCR2 could transfer tet(X5) into the recipient Acinetobacter baylyi ADP1 at a frequency of (1.8 ± 0.3)×10 -6 . Therefore, more efforts are needed to evaluate the clinical impact of these tigecycline resistance genes., (Copyright © 2020 Elsevier B.V. All rights reserved.)