Cytokine analysis of aqueous humor in patients with cytomegalovirus corneal endotheliitis.

PURPOSE: To evaluate cytokine levels of aqueous humor in patients with cytomegalovirus (CMV) corneal endotheliitis and their relationships with CMV DNA load. METHODS: 44 aqueous humor samples were obtained from 26 patients with CMV corneal endotheliitis at various stages of treatment. 33 samples obtained from cataract patients during the same period were selected as a control group. Each sample was used to measure the concentration of the CMV DNA load using real-time quantitative polymerase chain reaction, and to examine the levels of IL-6, IL-8, IL-10, MCP-1, VCAM-1, VEGF, IP-10, G-CSF, ICAM-1 and IFN-γ using a cytometric bead array. RESULTS: All 10 cytokines were found to have statistically significant differences between the CMV endotheliitis and cataract groups. The Spearman correlation test showed that the concentration of CMV DNA load was significantly associated with the levels of IL-6 (P = 0.005, r = 0.417), IL-8 (P < 0.001, r = 0.514), IL-10 (P < 0.001, r = 0.700), MCP-1 (P = 0.001, r = 0.487), VEGF (P < 0.001, r = 0.690), IP-10 (P = 0.001, r = 0.469), G-CSF (P < 0.001, r = 0.554) and ICAM-1 (P < 0.001, r = 0.635), but not significantly associated with VCAM-1 (P = 0.056) and IFN-γ (P = 0.219). CONCLUSIONS: There was a combined innate and adaptive immune response in aqueous humor in patients with CMV endotheliitis. Levels of multiple cytokines were significantly correlated with viral particle. Cytokines are potential indicators to help diagnose CMV endotheliitis, evaluate disease activity and assess treatment response.

Silica nanoparticles inhibit cadmium uptake by the protozoan Tetrahymena thermophila without the need for adsorption.

The simultaneous presence of nanoparticles (NPs) and heavy metals in the environment may affect their mutual biological uptake. Although previous studies showed that NPs could alter the cellular uptake of heavy metals by their adsorption of heavy metals, whether they could affect metal uptake without the need for adsorption is unknown. This study examined the effects of silica (SiO2) NPs on the uptake of Cd ion by the protozoan Tetrahymena thermophila. We found that, even with negligible levels of adsorption, SiO2 NPs at concentrations of 3 to 100 mg/L inhibited Cd uptake. This inhibitory effect decreased as the ambient Cd concentration increased from 1 to 100 µg/L, suggesting the involvement of at least two transporters with different affinities for Cd. The transporters were subsequently identified by the specific protein inhibitors amiloride and tariquidar as NCX and ABCB1, which are responsible for the uptake of Cd at low and high Cd levels, respectively. RT-qPCR and molecular dynamics simulation further showed that the inhibitory effects of SiO2 NPs were attributable to the down-regulated expression of the genes Ncx and Abcb1, steric hindrance of Cd uptake by NCX and ABCB1, and the shrinkage of the central channel pore of the transporters in the presence of SiO2 NPs. SiO2 NPs more strongly inhibited Cd transport by NCX than by ABCB1, due to the higher binding affinity of SiO2 NPs with NCX. Overall, our study sheds new light on a previously overlooked influence of NPs on metal uptake and the responsible mechanism.

Direct ammonia oxidation (Dirammox) is favored over cell growth in Alcaligenes ammonioxydans HO-1 to deal with the toxicity of ammonium.

Bacteria capable of direct ammonia oxidation (Dirammox) play important roles in global nitrogen cycling and nutrient removal from wastewater. Dirammox process, NH3 → NH2 OH → N2 , first defined in Alcaligenes ammonioxydans HO-1 and encoded by dnf gene cluster, has been found to widely exist in aquatic environments. However, because of multidrug resistance in Alcaligenes species, the key genes involved in the Dirammox pathway and the interaction between Dirammox process and the physiological state of Alcaligenes species remain unclear. In this work, ammonia removal via the redistribution of nitrogen between Dirammox and microbial growth in A. ammonioxydans HO-1, a model organism of Alcaligenes species, was investigated. The dnfA, dnfB, dnfC, and dnfR genes were found to play important roles in the Dirammox process in A. ammonioxydans HO-1, while dnfH, dnfG, and dnfD were not essential genes. Furthermore, an unexpected redistribution phenomenon for nitrogen between Dirammox and cell growth for ammonia removal in HO-1 was revealed. After the disruption of the Dirammox in HO-1, more consumed NH4 + was recovered as biomass-N via rapid metabolic response and upregulated expression of genes associated with ammonia transport and assimilation, tricarboxylic acid cycle, sulfur metabolism, ribosome synthesis, and other molecular functions. These findings deepen our understanding of the molecular mechanisms for Dirammox process in the genus Alcaligenes and provide useful information about the application of Alcaligenes species for ammonia-rich wastewater treatment.

Exploring the Molecular Mechanism of Niuxi-Mugua Formula in Treating Coronavirus Disease 2019 via Network Pharmacology, Computational Biology, and Surface Plasmon Resonance Verification.

BACKGROUND: In China, Niuxi-Mugua formula (NMF) has been widely used to prevent and treat coronavirus disease 2019 (COVID-19). However, the mechanism of NMF for treating COVID-19 is not yet fully understood. OBJECTIVE: This study aimed to explore the potential mechanism of NMF for treating COVID-19 by network pharmacology, computational biology, and surface plasmon resonance (SPR) verification. METHODS: The NMF-compound-target network was constructed to screen the key compounds, and the Molecular Complex Detection (MCODE) tool was used to screen the preliminary key genes. The overlapped genes (OGEs) and the preliminary key genes were further analyzed by enrichment analysis. Then, the correlation analysis of immune signatures and the preliminary key genes was performed. Molecular docking and molecular dynamic (MD) simulation assays were applied to clarify the interactions between key compounds and key genes. Moreover, the SPR interaction experiment was used for further affinity kinetic verification. RESULTS: Lipid and atherosclerosis, TNF, IL-17, and NF-kappa B signaling pathways were the main pathways of NMF in the treatment of COVID-19. There was a positive correlation between almost the majority of immune signatures and all preliminary key genes. The key compounds and the key genes were screened out, and they were involved in the main pathways of NMF for treating COVID-19. Moreover, the binding affinities of most key compounds binding to key genes were good, and IL1B-Quercetin had the best binding stability. SPR analysis further demonstrated that IL1B-Quercetin showed good binding affinity. CONCLUSION: Our findings provided theoretical grounds for NMF in the treatment of COVID19.

Identification of potential pathogenic targets and survival strategies of Vibrio vulnificus through population genomics.

Vibrio vulnificus, a foodborne pathogen, has a high mortality rate. Despite its relevance to public health, the identification of virulence genes associated with the pathogenicity of currently known clinical isolates of V. vulnificus is incomplete and its synergistic pathogenesis remains unclear. Here, we integrate whole genome sequencing (WGS), genome-wide association studies (GWAS), and genome-wide epistasis studies (GWES), along with phenotype characterization to investigate the pathogenesis and survival strategies of V. vulnificus. GWAS and GWES identified a total of six genes (purH, gmr, yiaV, dsbD, ramA, and wbpA) associated with the pathogenicity of clinical isolates related to nucleotide/amino acid transport and metabolism, cell membrane biogenesis, signal transduction mechanisms, and protein turnover. Of these, five were newly discovered potential specific virulence genes of V. vulnificus in this study. Furthermore, GWES combined with phenotype experiments indicated that V. vulnificus isolates were clustered into two ecological groups (EGs) that shared distinct biotic and abiotic factors, and ecological strategies. Our study reveals pathogenic mechanisms and their evolution in V. vulnificus to provide a solid foundation for designing new vaccines and therapeutic targets.

Spatial distribution pattern and correlation of dominant species in the arbor layer at a 25 hm2 forest plot in Lushan Mountain, China.

To explore the spatial pattern of zonal tree species in the subtropical subalpine mountain area on Lushan Mountain, a 25 hm2 forest plot was established in Yangtianping area of Lushan Mountain following the technical specification of CTFS in 2021. We classified these species into evergreen conifer species, deciduous broad-leaved species and evergreen broad-leaved species based on their leaf shape and deciduous or not to analyze the spatial pattern of dominant species of different types by spatial point pattern method. The results showed that Pinus taiwanensis, Cornus kousa subsp. chinensis, Platycarya strobilacea, Castanea henryi, Quercus serrata, Cornus controversa, Eurya muricata, Litsea elongata, and Eurya hebeclados were dominant species. Among these species, P. taiwanensis was the constructive one. The spatial pattern of dominant species was clustered at a certain scale, and gradually became to randomly distribution with the increases of scales. Evergreen conifer species was independent with deci-duous broad-leaved species and evergreen broad-leaved species at small scales, but was negatively correlated with them at large scales. Deciduous broad-leaved species and evergreen broad-leaved species were obviously negatively correlated with each other. Deciduous broad-leaved species were positively correlated or independent with each other at small scales, but were negatively correlated with each other at large scales. Evergreen broad-leaved species were positively correlated at small scales, independent at medium scales, and negatively correlated with each other at large scales.

A longitudinal resource for population neuroscience of school-age children and adolescents in China.

During the past decade, cognitive neuroscience has been calling for population diversity to address the challenge of validity and generalizability, ushering in a new era of population neuroscience. The developing Chinese Color Nest Project (devCCNP, 2013-2022), the first ten-year stage of the lifespan CCNP (2013-2032), is a two-stages project focusing on brain-mind development. The project aims to create and share a large-scale, longitudinal and multimodal dataset of typically developing children and adolescents (ages 6.0-17.9 at enrolment) in the Chinese population. The devCCNP houses not only phenotypes measured by demographic, biophysical, psychological and behavioural, cognitive, affective, and ocular-tracking assessments but also neurotypes measured with magnetic resonance imaging (MRI) of brain morphometry, resting-state function, naturalistic viewing function and diffusion structure. This Data Descriptor introduces the first data release of devCCNP including a total of 864 visits from 479 participants. Herein, we provided details of the experimental design, sampling strategies, and technical validation of the devCCNP resource. We demonstrate and discuss the potential of a multicohort longitudinal design to depict normative brain growth curves from the perspective of developmental population neuroscience. The devCCNP resource is shared as part of the "Chinese Data-sharing Warehouse for In-vivo Imaging Brain" in the Chinese Color Nest Project (CCNP) - Lifespan Brain-Mind Development Data Community ( https://ccnp.scidb.cn ) at the Science Data Bank.

Glucose metabolism profile recorded by flash glucose monitoring system in patients with hypopituitarism during prednisone replacement.

BACKGROUND: Commonly used glucocorticoids replacement regimens in patients with hypopituitarism have difficulty mimicking physiological cortisol rhythms and are usually accompanied by risks of over-treatment, with adverse effects on glucose metabolism. Disorders associated with glucose metabolism are established risk factors of cardiovascular events, one of the life-threatening ramifications. AIM: To investigate the glycometabolism profile in patients with hypopituitarism receiving prednisone (Pred) replacement, and to clarify the impacts of different Pred doses on glycometabolism and consequent adverse cardiovascular outcomes. METHODS: Twenty patients with hypopituitarism receiving Pred replacement [patient group (PG)] and 20 normal controls (NCs) were recruited. A flash glucose monitoring system was used to record continuous glucose levels during the day, which provided information on glucose-target-rate, glucose variability (GV), period glucose level, and hypoglycemia occurrence at certain periods. Islet ß-cell function was also assessed. Based on the administered Pred dose per day, the PG was then regrouped into Pred > 5 mg/d and Pred ≤ 5 mg/d subgroups. Comparative analysis was carried out between the PG and NCs. RESULTS: Significantly altered glucose metabolism profiles were identified in the PG. This includes significant reductions in glucose-target-rate and nocturnal glucose level, along with elevations in GV, hypoglycemia occurrence and postprandial glucose level, when compared with those in NCs. Subgroup analysis indicated more significant glucose metabolism impairment in the Pred > 5 mg/d group, including significantly decreased glucose-target-rate and nocturnal glucose level, along with increased GV, hypoglycemia occurrence, and postprandial glucose level. With regard to islet ß-cell function, PG showed significant difference in homeostasis model assessment (HOMA)-ß compared with that of NCs; a notable difference in HOMA-ß was identified in Pred > 5 mg/d group when compared with those of NCs; as for Pred ≤ 5 mg/d group, significant differences were found in HOMA-ß, and fasting glucose/insulin ratio when compared with NCs. CONCLUSION: Our results demonstrated that Pred replacement disrupted glycometabolic homeostasis in patients with hypopituitarism. A Pred dose of > 5 mg/d seemed to cause more adverse effects on glycometabolism than a dose of ≤ 5 mg/d. Comprehensive and accurate evaluation is necessary to consider a suitable Pred replacement regimen, wherein, flash glucose monitoring system is a kind of promising and reliable assessment device. The present data allows us to thoroughly examine our modern treatment standards, especially in difficult cases such as hormonal replacement mimicking delicate natural cycles, in conditions such as diabetes mellitus that are rapidly growing in worldwide prevalence.

Detection of Burkholderia pseudomallei with CRISPR-Cas12a based on specific sequence tags.

Melioidosis is a bacterial infection caused by Burkholderia pseudomallei (B. pseudomallei), posing a significant threat to public health. Rapid and accurate detection of B. pseudomallei is crucial for preventing and controlling melioidosis. However, identifying B. pseudomallei is challenging due to its high similarity to other species in the same genus. To address this issue, this study proposed a dual-target method that can specifically identify B. pseudomallei in less than 40 min. We analyzed 1722 B. pseudomallei genomes to construct large-scale pan-genomes and selected specific sequence tags in their core genomes that effectively distinguish B. pseudomallei from its closely related species. Specifically, we selected two specific tags, LC1 and LC2, which we combined with the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR associated proteins (Cas12a) system and recombinase polymerase amplification (RPA) pre-amplification. Our analysis showed that the dual-target RPA-CRISPR/Cas12a assay has a sensitivity of approximately 0.2 copies/reaction and 10 fg genomic DNA for LC1, and 2 copies/reaction and 20 fg genomic DNA for LC2. Additionally, our method can accurately and rapidly detect B. pseudomallei in human blood and moist soil samples using the specific sequence tags mentioned above. In conclusion, the dual-target RPA-CRISPR/Cas12a method is a valuable tool for the rapid and accurate identification of B. pseudomallei in clinical and environmental samples, aiding in the prevention and control of melioidosis.

Comparative Analysis of the Interfacial Structure and Properties of BiOX/BiOY (X, Y = F, Cl, Br, and I) Heterostructures through DFT Calculations.

This study focuses on the systematic investigation of the microstructure, interfacial energy, and electronic structure of six BiOX/BiOY heterostructures constructed using four bismuth oxyhalide materials. Utilizing density functional theory (DFT) calculations, the study provides fundamental insights into the interfacial structure and properties of these heterostructures. The results indicate that the formation energies of BiOX/BiOY heterostructures decrease in the order of BiOF/BiOI, BiOF/BiOBr, BiOF/BiOCl, BiOCl/BiOBr, BiOBr/BiOI, and BiOCl/BiOI. BiOCl/BiBr heterostructures were found to have the lowest formation energy and were the most easily formed. Conversely, the formation of BiOF/BiOY heterostructures was observed to be unstable and difficult to achieve. Furthermore, the interfacial electronic structure analysis revealed that BiOCl/BiOBr, BiOCl/BiOI, and BiOBr/BiOI displayed opposite electric fields that facilitated electron-hole pair separation. Therefore, these research findings provide a comprehensive understanding of the mechanisms underlying the formation of BiOX/BiOY heterostructures and present theoretical guidance for the design of innovative and efficient photocatalytic heterostructures, with an emphasis on BiOCl/BiOBr heterostructures. This study highlights the advantages of distinctively layered BiOX materials and their heterostructures, which offer a wide range of band gap values, and demonstrates their potential for various research and practical applications.

Endovascular repair of aortic pathologies involving the aortic arch using castor stent-graft combined with in-vitro fenestration technology.

BACKGROUND: Aortic arch pathologies are concerning clinical conditions with poor prognoses. The use of thoracic endovascular aortic repair (TEVAR) has been investigated to treat aortic arch pathologies. Nonetheless, cerebral blood flow regulation during endovascular aortic arch repair therapy remains challenging. Castor, a unique single-branched stent graft, has been proven effective for retaining the left subclavian artery (LSA). This study aimed to determine whether endovascular therapy for pathologies involving the aortic arch using Castor in combination with the in-vitro fenestration technique is promising, effective, and safe. METHODS: Eligible patients were enrolled between June 2018 and December 2021. All patients underwent TEVAR with an evaluated proximal landing zone for "Castor" located in Ishimaru zones 0-1. Moreover, the supra-aortic branches (SABs) were reconstructed using the Castor in combination with the in-vitro fenestration technique. RESULTS: Herein, 57 patients with aortic arch lesions were treated with Castor in combination with the in-vitro fenestration technique. Innominate artery and the left carotid artery (LCA) were reconstructed in 5 patients, LCA and left subclavian artery (LSA) were reconstructed in 22 patients, and the total SABs were effectively reconstructed in 30 patients (including a hybrid arch repair case). Among them (excluding a hybrid arch repair case) were in-vitro fenestration methodologies for LCA in 32 of 34 cases (2 switched to in-situ fenestration) and LSA in 51 of 56 cases (3 switched to in-situ fenestration and 2 converted to spring coil caulking); furthermore, LCA and LSA in-vitro fenestration were simultaneously successfully performed in 27 of 34 cases. There were no surgical-related neurological complications, and early mortality was estimated at 5.26%. At a mean follow-up of 3.75 months, computed tomography (CTA) images confirmed that each branch stent remained patent. There were no signs of endoleaks, migrative manifestations, or the need for secondary endovascular intervention or conversion to open surgical procedures. CONCLUSION: Castor, in combination with in-vitro fenestration, reflects a feasible, efficient procedure for re-developing SABs.

Effects of exergame and bicycle exercise intervention on blood pressure and executive function in older adults with hypertension: A three-group randomized controlled study.

Management of hypertension and prevention of cognitive decline are challenging public health problems. However, the effects of exergame intervention on blood pressure (BP) remain to be explored, and whether exergame intervention is an effective alternative to traditional physical exercise intervention for older adults with hypertension remains to be demonstrated. This study aimed to explore the effectiveness of moderate-intensity exergame intervention and bicycle exercise training on BP and executive function in older hypertensive patients. A total of 128 participants were randomly assigned to the exergame intervention group (n = 41), bicycle exercise intervention group (n = 44), and control group (n = 43). The intervention groups exercised for 60 min, 3 times per week, for 16 weeks, while the control group maintained their normal lifestyle. The results revealed that there were no significant differences between two intervention groups and control group in systolic BP and diastolic BP changes (ps > 0.05). Both intervention groups demonstrated significant improvements in working memory when compared with control group (exergame intervention group: -461.9 ms, p = 0.025; bicycle exercise intervention group: -470.1 ms, p = 0.021). There were no significant differences in systolic BP, diastolic BP, or working memory between the two intervention groups after 16 weeks of training (ps > 0.05). No difference in inhibition or cognitive flexibility was observed between the intervention and control groups (ps > 0.05). The current results showed that moderate-intensity exergame intervention did not produce significant benefits in reducing BP, but yielded similar beneficial effects in working memory to that of bicycle exercise intervention. More studies are needed on whether exergame intervention has the potential to be a promising supplemental therapeutic tool for older adults with hypertension.

Surgical site infection after intracorporeal anastomosis for left-sided colon cancer: study protocol for a non-inferiority multicenter randomized controlled trial (STARS).

BACKGROUND: Surgical site infection (SSI), as one of the most common hospital-acquired infection, is usually associated with increased morbidity, mortality, and health care burden. SSI is a significant perioperative complication after colon cancer surgery, particularly for left-sided colon cancer. This paper describes the background and design of the "Surgical Site Infection after intracorporeal anastomosis for Left-sided Colon Cancer: study protocol for a non-inferiority multicenter Randomized Controlled Trial (STARS)." The STARS trial aims to compare the incidence of SSI after intracorporeal anastomosis and extracorporeal anastomosis after radical resection of colon cancer and to explore the risk factors of SSI. METHODS: A total of 354 left colon cancer patients from 8 hospitals in China will be enrolled in this multi-center randomized controlled study. The primary outcome of this study is the incidence of SSI 30 days after left-sided colon cancer surgery. Secondary outcome measures include operation time, blood loss, conversion rate, incidence of perioperative complications, completeness of resection, number of lymph nodes collected and postoperative recovery characteristics, 3-year disease-free survival, and 5-year overall survival. The first patient was enrolled in January 2021. DISCUSSION: To our knowledge, this is the first prospective multicenter study to investigate whether there is a difference in the SSI incidence after intracorporeal and extracorporeal anastomosis for left-sided colon cancer in China. The results may provide more evidence that supports performing total laparoscopic left-sided colon cancer surgery. TRIAL REGISTRATION: The trial has been registered on ClinicalTrials.gov website (ID: NCT04201717). Registered on September 22, 2020.

Transcriptome-Wide Characterization of piRNAs during the Developmental Process of European Honey-Bee Larval Guts.

piRNAs play pivotal roles in maintaining genome stability, regulating gene expression, and modulating development and immunity. However, there are few piRNA-associated studies on honey-bees, and the regulatory role of piRNAs in the development of bee guts is largely unknown. Here, the differential expression pattern of piRNAs during the developmental process of the European honey-bee (Apis mellifera) larval guts was analyzed, followed by investigation of the regulatory network and the potential function of differentially expressed piRNAs (DEpiRNAs) in regulating gut development. A total of 843 piRNAs were identified in the larval guts of A. mellifera; among these, 764 piRNAs were shared by 4- (Am4 group), 5- (Am5 group), and 6-day-old (Am6 group) larval guts, while 11, 67, and one, respectively, were unique. The first base of piRNAs in each group had a cytosine (C) bias. Additionally, 61 up-regulated and 17 down-regulated piRNAs were identified in the "Am4 vs. Am5" comparison group, further targeting 9, 983 genes, which were involved in 50 GO terms and 142 pathways, while two up-regulated and five down-regulated piRNAs were detected in the "Am5 vs. Am6" comparison group, further targeting 1, 936 genes, which were engaged in 41 functional terms and 101 pathways. piR-ame-742536 and piR-ame-856650 in the "Am4 vs. Am5" comparison group as well as piR-ame-592661 and piR-ame-31653 in the "Am5 vs. Am6" comparison group were found to link to the highest number of targets. Further analysis indicated that targets of DEpiRNAs in these two comparison groups putatively regulate seven development-associated signaling pathways, seven immune-associated pathways, and three energy metabolism pathways. Moreover, the expression trends of five randomly selected DEpiRNAs were verified based on stem-loop RT-PCR and RT-qPCR. These results were suggestive of the overall alteration of piRNAs during the larval developmental process and demonstrated that DEpiRNAs potentially modulate development-, immune-, and energy metabolism-associated pathways by regulating the expression of corresponding genes via target binding, further affecting the development of A. mellifera larval guts. Our data offer a novel insight into the development of bee larval guts and lay a basis for clarifying the underlying mechanisms.

Detection and Quantification of Antimicrobial-Resistant Cells in Aquatic Environments by Bioorthogonal Noncanonical Amino Acid Tagging.

Aquatic environments are important reservoirs of antibiotic wastes, antibiotic resistance genes, and bacteria, enabling the persistence and proliferation of antibiotic resistance in different bacterial populations. To prevent the spread of antibiotic resistance, effective approaches to detect antimicrobial susceptibility in aquatic environments are highly desired. In this work, we adopt a metabolism-based bioorthogonal noncanonical amino acid tagging (BONCAT) method to detect, visualize, and quantify active antimicrobial-resistant bacteria in water samples by exploiting the differences in bacterial metabolic responses to antibiotics. The BONCAT approach can be applied to rapidly detect bacterial resistance to multiple antibiotics within 20 min of incubation, regardless of whether they act on proteins or DNA. In addition, the combination of BONCAT with the microscope enables the intuitive characterization of antibiotic-resistant bacteria in mixed systems at single-cell resolution. Furthermore, BONCAT coupled with flow cytometry exhibits good performance in determining bacterial resistance ratios to chloramphenicol and population heterogeneity in hospital wastewater samples. In addition, this approach is also effective in detecting antibiotic-resistant bacteria in natural water samples. Therefore, such a simple, fast, and efficient BONCAT-based approach will be valuable in monitoring the increase and spread of antibiotic resistance within natural and engineered aquatic environments.

[Effects of Trichoderma on nitrogen absorption and use efficiency in Lycium chinense roots under saline stress]. / æœ¨éœ‰å¯¹ç›æ¸é€†å¢ƒä¸‹æž¸æžæ ¹ç³»æ°®ç´ å¸æ”¶å’Œæ°®ç´ åˆ©ç”¨æ•ˆçŽ‡çš„å½±å“.

To clarify the mechanisms underlying the improvement of Trichoderma on Chinese wolfberry (Lycium chinense) growth under saline stress, we analyzed the effects of application of organic fertilizer, Trichoderma agent and fertilizer on nitrogen uptake, assimilation, accumulation and use efficiency in Chinese wolfberry, based on a pot experiment with coastal saline soil. The organic fertilizer was the sterilization substance of Trichoderma fertilizer without viable Trichoderma, without any difference in the content of nutrients (such as nitrogen, phosphorus and potassium) between them. The results showed that the application of organic fertilizer, Trichoderma agent and ferti-lizer significantly increased NO3- and NH4+ influx rate in meristematic zone and NO3- influx rate in maturation zone of roots. The magnitude of such enhancement was greater in the application with Trichoderma fertilizer than organic fertilizer. Compared with the control, the application of Trichoderma agent and fertilizer significantly increased root, stem and leaf biomass and nitrogen content as well as plant nitrogen accumulation, strengthened root and leaf nitrate reductase, nitrite reductase and glutamine synthetase activities, and elevated nitrogen uptake efficiency, photosynthetic rate, stable carbon isotope abundance and photosynthetic nitrogen use efficiency. For all those variables, the beneficial effect was obviously stronger in the application with Trichoderma fertilizer than organic fertilizer. Therefore, Trichoderma facilitated nitrogen uptake, assimilation and accumulation in Chinese wolfberry under saline stress, improved photosynthetic carbon fixation ability and nitrogen use efficiency, and ultimately promoted plant growth.

Heat stress in broilers of liver injury effects of heat stress on oxidative stress and autophagy in liver of broilers.

This study aimed to investigate the effect of chronic heat stress on oxidative stress in liver of broilers. In our study, chickens were randomly allocated to control 1 group (control 7 d), heat stress 1 group (HS1, 7 d), control 2 group (control 14 d) and heat stress 2 group (HS2, 14 d), with 30 replicates in each group. Broilers in heat stress groups exposed 8 h/day heat stress (35 ± 2°C) for 7 or 14 consecutive days, and the rest of time per day were kept at 23 ± 2℃ the same as control group broilers. Growth performance and the liver tissues were collected for histological observation and detection of organ index and liver redox status. The serum indicators (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) related to liver injury were determined. Moreover, Nrf2-related genes and protein expression levels in liver were measured. The results showed that in heat stress group broilers the body weight gain, feed conversion ratio, liver weight, and liver index were decreased, inflammatory cells infiltration in liver, and serum AST level was enhanced, compared with control group broilers. Moreover, the hepatic malondialdehyde (MDA) and superoxide dismutase (SOD) level were increased after 1 wk of heat stress. Nrf2, Sqstm1/p62, HO-1, and NQO1 mRNA expressions in the liver of broilers were decreased by heat stress. P62 and p-p62 protein expressions were significantly up-regulated, but Nrf2 and keap1 protein level was decreased in heat stress group broilers as compared to control group. The mRNA expression levels of Beclin1, LC3-I, LC3-II were down-regulated significantly with heat stress for 1 wk. The mRNA expression level of mTOR up-regulated after 2 wk of heat stress. In conclusion, heat stress induced liver injury of broilers by down-regulating Nrf2-keap1 signaling pathway and autophagy.

Leonurine Attenuates Obesity-Related Vascular Dysfunction and Inflammation.

Oxidative stress in adipose tissue is a crucial pathogenic mechanism of obesity-associated cardiovascular diseases. Chronic low-grade inflammation caused by obesity increases ROS production and dysregulation of adipocytokines. Leonurine (LEO) is an active alkaloid extracted from Herba Leonuri and plays a protective role in the cardiovascular system. The present study tested whether LEO alleviates inflammation and oxidative stress, and improves vascular function in an obese mouse model. Here, we found that obesity leads to inflammation and oxidative stress in epididymal white adipose tissue (EWAT), as well as vascular dysfunction. LEO significantly improved inflammation and oxidative stress both in vivo and in vitro. Obesity-induced vascular dysfunction was also improved by LEO as evidenced by the ameliorated vascular tone and decreased mesenteric artery fibrosis. Using mass spectrometry, we identified YTHDF1 as the direct target of LEO. Taken together, we demonstrated that LEO improves oxidative stress and vascular remodeling induced by obesity and targets YTHDF1, raising the possibility of LEO treating other obesity-related metabolic syndromes.

Dexmedetomidine Attenuates Ferroptosis-Mediated Renal Ischemia/Reperfusion Injury and Inflammation by Inhibiting ACSL4 via α2-AR.

Ischemia-reperfusion (I/R) injury is a serious clinical pathology associated with acute kidney injury (AKI). Ferroptosis is non-apoptotic cell death that is known to contribute to renal I/R injury. Dexmedetomidine (Dex) has been shown to exert anti-inflammatory and organ protective effects. This study aimed to investigate the detailed molecular mechanism of Dex protects kidneys against I/R injury through inhibiting ferroptosis. We established the I/R-induced renal injury model in mice, and OGD/R induced HEK293T cells damage in vitro. RNA-seq analysis was performed for identifying the potential therapeutic targets. RNA-seq analysis for differentially expressed genes (DEGs) reported Acyl-CoA synthetase long-chain family member 4 (ACSL4) related to ferroptosis and inflammation in I/R mice renal, which was validated in rodent renal. Liproxstatin-1, the specific small-molecule inhibitor of ferroptosis, significantly attenuated ferroptosis-mediated renal I/R injury with decreased LPO, MDA, and LDH levels, and increased GSH level. Inhibiting the activity of ACSL4 by the Rosiglitazone (ROSI) resulted in the decreased ferroptosis and inflammation, as well as reduced renal tissue damage, with decreasing LPO, MDA and LDH level, increasing GSH level, reducing COX2 and increasing GPx4 protein expression, and suppressing the TNF-α mRNA and IL-6 mRNA levels. Dex as a α2-adrenergic receptor (α2-AR) agonist performed renal protective effects against I/R-induced injury. Our results also revealed that Dex administration mitigated tissue damage, inhibited ferroptosis, and downregulated inflammation response following renal I/R injury, which were associated with the suppression of ACSL4. In addition, ACSL4 overexpression abolishes Dex-mediated protective effects on OGD/R induced ferroptosis and inflammation in HEK293T cells, and promotion of ACSL4 expression by α2-AR inhibitor significantly reversed the effects on the protective role of Dex. This present study indicated that the Dex attenuates ferroptosis-mediated renal I/R injury and inflammation by inhibiting ACSL4 via α2-AR.

A N7-Methylguanine-Related Gene Signature Applicable for the Prognosis and Microenvironment of Prostate Cancer.

Background: Despite the constant iteration of small-molecule inhibitors and immune checkpoint inhibitors, PRAD (prostate adenocarcinoma) patients with distant metastases and biochemical recurrence maintain a poor survival outcome along with an increasing morbidity in recent years. N7-Methylguanine, a new-found type of RNA modification, has demonstrated an essential role in tumor progression but has hardly been studied for its effect on prostate carcinoma. The current study aimed to seek m7G (N7-methylguanosine) related prognostic biomarkers and potential targets for PRAD treatment. Methods: 42 genes related to m7G were collected from former literatures and GSEA (Gene Set Enrichment Analysis) website. Then, RNA-seq (RNA sequencing) and clinical data from TCGA-PRAD (The Cancer Genome Atlas-Prostate) cohort were retrieved to screen the differentially expressed m7G genes to further construct a multivariate Cox prognostic model for PRAD. Next, GSE116918, a prostate cancer cohort acquired from GEO (Gene Expression Omnibus) database, was analyzed for the external validation group to assess the ability to predict BFFS (biochemical failure-free survival) of our m7G prognostic signature. Kaplan-Meier, ROC (receiver operator characteristic), AUC (areas under ROC curve), and calibration curves were adopted to display the performance of this prognostic signature. In addition, immune infiltration analysis was implemented to evaluate the effect of these m7G genes on immunoinfiltrating cells. Correlation with drug susceptibility of the m7G signature was also analyzed by matching drug information in CellMiner database. Results: The m7G-related prognostic signature, including three genes (EIF3D, EIF4A1, LARP1) illustrated superior prognostic ability for PRAD in both training and validation cohorts. The 5-year AUC were 0.768 for TCGA-PRAD and 0.608 for GSE116918. It can well distinguish patients into different risk groups of biochemical recurrence (p =1e-04 for TCGA-PRAD and p =0.0186 for GSE116918). Immune infiltration analysis suggested potential regulation of m7G genes on neutrophils and dendritic cells in PRAD. Conclusions: A m7G-related prognostic signature was constructed and validated in the current study, giving new sights of m7G methylation in predicting the prognostic and improving the treatment of PRAD.