Search

Prehistoric settlement patterns on the Tibetan Plateau, particularly in the Qaidam Basin, have drawn significant scholarly interest. Yet, limited data have hindered a comprehensive understanding the Bronze Age chronology and landscape exploitation in this region. This paper presents 24 newly obtained radiocarbon dates from eight archaeological sites within the Qaidam Basin on the Tibetan Plateau. Integrated with existing 14 C data and spatial analysis, these findings reveal an overall continuous occupation of the basin from ca. 3600-2500 calBP, with a gradual shift from expansive lowland settlements to smaller, ephemeral high-altitude structures, identified around 3350 calBP. This change is consistent with demonstrated periods of climate degradation which likely drove strategic adaptations in landscape management and subsistence methods. Overall, this research not only establishes a more robust chronology for the Qaidam Basin's Bronze Age, but also advances the discussion on human-environment interactions in high-altitude areas during late prehistory., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

The emergence of Staphylococcus epidermidis as a significant nosocomial pathogen necessitates advancements in more efficient antimicrobial resistance profiling. However, existing culture-based and PCR-based antimicrobial susceptibility testing methods are far too slow or costly. This study combines machine learning with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to develop predictive models for various antibiotics using a comprehensive dataset containing thousands of S. epidermidis isolates. Optimized machine learning models utilized feature selection and achieved high AUROC scores ranging from 0.80 to 0.95 while maintaining AUPRC scores up to 0.97. Shapley Additive exPlanations were employed to analyze relevant features and assess the significance of corresponding protein biomarkers while also verifying that predictive power was derived from the detection of proteins rather than noise. Antimicrobial resistance models were validated externally to evaluate model performance outside the original data collection site. The approaches and findings in this study demonstrate a significant advancement in rapid, cost-effective antimicrobial resistance profiling, offering a promising solution for improving treatments for nosocomial infections and being potentially applicable to other microbial pathogens in the future., (© 2024. The Author(s).)

Sorghum is the world's fifth-largest cereal crop, and anthracnose (Colletotrichum sublineola) is the main disease affecting sorghum. However, systematic research on the cellular structure, physiological and biochemical, and genes related to anthracnose resistance and disease resistance evaluation in sorghum is lacking in the field. Upon inoculation with anthracnose (C. sublineola) spores, disease-resistant sorghum (gz93) developed a relative lesion area (RLA) that was significantly smaller than that of the disease-susceptible sorghum (gz234). The leaf thickness, length and profile area of leaf mesophyll cells, upper and lower epidermal cells decreased in the lesion area, with a greater reduction observed in gz234 than in gz93. The damage caused by C. sublineola resulted in a greater decrease in the net photosynthetic rate (Pn) in gz234 than in gz93, with early-stage reduction due to stomatal limitation and late-stage reduction caused by lesions. Overall, the activities of superoxide dismutase (SOD) and catalase (CAT), the content of proline (Pro), abscisic acid (ABA), jasmonic acid (JA), salicylic acid (SA), and gibberellic acid (GA 3 ), are higher in gz93 than in gz234 and may be positively correlated with disease resistance. While malondialdehyde (MDA) may be negatively correlated with disease resistance. Disease-resistant genes are significantly overexpressed in gz93, with significant expression changes in gz234, which is related to disease resistance in sorghum. Correlation analysis indicates that GA 3 , MDA, peroxidase (POD), and disease-resistance genes can serve as reference indicators for disease severity. The regression equation RLA = 0.029 + 8.02 × 10 -6 JA-0.016 GA 3 can predict and explain RLA. Principal component analysis (PCA), with the top 5 principal components for physiological and biochemical indicators and the top 2 principal components for disease-resistant genes, can explain 82.37% and 89.11% of their total variance, reducing the number of evaluation indicators. This study provides a basis for research on the mechanisms and breeding of sorghum with resistance to anthracnose., (© 2024. The Author(s).)

Rituximab occasionally induces reactivation of hepatitis C virus (HCV) in patients with resolved HCV infection, sometimes with fatal consequences. As rituximab has become one of the first-line therapies for the treatment of phospholipase A2 receptor (PLA2R)-associated membranous nephropathy (MN) and is more widely used, there is a lack of studies reporting the effectiveness and safety of rituximab in patients with PLA2R-associated MN and resolved HCV infection. A single-center retrospective study was conducted on PLA2R-associated membranous nephropathy (MN) patients who were HCVAb positive but HCV-RNA negative and treated with rituximab. A total of 598 adult patients with PLA2R-associated MN who underwent rituximab therapy were screened. General clinical information, including gender, age, pathological data, and previous treatment plans, was collected from medical records. Routine blood tests, liver and kidney function assessments, blood lipid profiles, 24-h urine protein levels, anti-PLA2R antibody titers, circulating B-cell counts, and HCV viral loads were measured at the time of rituximab infusion and repeated at intervals of 1-3 months post-rituximab administration. A total of 8 patients were enrolled, with a median follow-up period of 19.00 (range: 16.00-25.25) months. Among the 8 patients, 5 were male, and the mean age was 50.13 ± 4.29 years. Histological findings indicated that tubuloreticular inclusions, mesangial deposits, intramembranous deposits, and subendothelial deposits were not observed in any of the 8 patients. The overall 1-year remission rate for these patients was 75%, accompanied by a significant reduction in proteinuria. Additionally, blood albumin levels increased significantly, and renal function remained stable. No increase in HCV viral load and stable liver function tests were observed throughout the entire follow-up period. This study suggested that on the basis of successful eradication of HCV virus with antiviral drugs, rituximab can effectively induce clinical remission of patients with PLA2R associated MN and resolved HCV infection, and does not lead to a significant increase in HCV virus load. However, this finding is based on a very small sample size and should be confirmed in larger clinical trials., (© 2024. The Author(s).)

The impact of premade beef patty (BBP) with red onion skin powder (OSP) at 0, 1, 2, and 3% levels on color, lipid, and protein oxidative stability, and infection degree of microorganisms during cold storage was investigated. The objective was to determine the effect of color by L*, a*, b*, and the content of MetMb. The inhibitory effect of OSP on the oxidation of lipid and protein was studied based on TBARS and the carbonyl content of protein in samples at different storage times. TVB-N content was used to characterize the degree of infection of microorganisms and their effect on meat quality. The results showed that the addition of OSP reduced the pH, L *, a*, and b * values of BBP, and improved the hardness, springiness, gumminess, and cohesiveness of BBP, but had no significant effect on the chewiness of BBP (p > 0.05). After 12 days of storage, the carbonyl group and TBARS content in the BBP supplemented with 3%OSP was significantly lower than that in the control group (p < 0.05). Furthermore, the addition of OSP significantly inhibited the TVB-N increase during beef patty storage. These results indicated that OSP has a good research prospect as a natural antioxidant or preservative., (© 2024. The Author(s).)

Barth syndrome (BTHS) is a rare disorder caused by mutations in the TAFAZZIN gene. Previous studies from both patients and model systems have established metabolic dysregulation as a core component of BTHS pathology. In particular, features such as lactic acidosis, pyruvate dehydrogenase (PDH) deficiency, and aberrant fatty acid and glucose oxidation have been identified. However, the lack of a mechanistic understanding of what causes these conditions in the context of BTHS remains a significant knowledge gap, and this has hindered the development of effective therapeutic strategies for treating the associated metabolic problems. In the current study, we utilized tafazzin-knockout C2C12 mouse myoblasts (TAZ-KO) and cardiac and skeletal muscle tissue from tafazzin-knockout mice to identify an upstream mechanism underlying impaired PDH activity in BTHS. This mechanism centers around robust upregulation of pyruvate dehydrogenase kinase 4 (PDK4), resulting from hyperactivation of AMP-activated protein kinase (AMPK) and subsequent transcriptional upregulation by forkhead box protein O1 (FOXO1). Upregulation of PDK4 in tafazzin-deficient cells causes direct phospho-inhibition of PDH activity accompanied by increased glucose uptake and elevated intracellular glucose concentration. Collectively, our findings provide a novel mechanistic framework whereby impaired tafazzin function ultimately results in robust PDK4 upregulation, leading to impaired PDH activity and likely linked to dysregulated metabolic substrate utilization. This mechanism may underlie previously reported findings of BTHS-associated metabolic dysregulation., (© 2024. The Author(s).)

Ovarian cancer (OC) is one of the most prevalent and fatal malignant tumors of the female reproductive system. Our research aimed to develop a prognostic model to assist inclinical treatment decision-making.Utilizing data from The Cancer Genome Atlas (TCGA) and copy number variation (CNV) data from the University of California Santa Cruz (UCSC) database, we conducted analyses of differentially expressed genes (DEGs), gene function, and tumor microenvironment (TME) scores in various clusters of OC samples.Next, we classified participants into low-risk and high-risk groups based on the median risk score, thereby dividing both the training group and the entire group accordingly. Overall survival (OS) was significantly reduced in the high-risk group, and two independent prognostic factors were identified: age and risk score. Additionally, three genes-C-X-C Motif Chemokine Ligand 10 (CXCL10), RELB, and Caspase-3 (CASP3)-emerged as potential candidates for an independent prognostic signature with acceptable prognostic value. In Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, pathways related to immune responses and inflammatory cell chemotaxis were identified. Cellular experiments further validated the reliability and precision of our findings. In conclusion, necroptosis-related genes play critical roles in tumor immunity, and our model introduces a novel strategy for predicting the prognosis of OC patients., (© 2024. The Author(s).)

The IPv6 extension header mechanism, a new feature of the IPv6 protocol, enhances flexibility and scalability but introduces numerous security threats like firewall evasion and covert channels. Existing threat detection methods face limitations in detection types, universality, and speed. Hence, an adaptive detection model for IPv6 extension header threats (ADM-DDA6) is proposed. Firstly, standard rule sets are designed for common IPv6 extension headers, successfully detecting 70 types of threats from THC-IPv6 and ExtHdr tools using only 20 rules. Secondly, by parsing IPv6 extension headers, matching rules, establishing transition relationships, and deciding packet threat status based on final states (Normal or Abnormal), complex threats like header disorder and header repetition can be detected. Finally, an adaptive rule matching method is introduced, which dynamically selects rule sets based on IPv6 extension header types, effectively reducing rule matching time. Experimental results show that under different threat magnitudes, ADM-DDA6 is 32% faster than Suricata v6.0.12 and 21.2% faster than Snort v3.1.61.0 in detection speed. Additionally, as the number of threats increases, on commodity hardware, ADM-DDA6 incurs only a 0.7% increase in CPU overhead with no significant memory consumption increase, maintains maximum throughput, and exhibits minor performance changes under low and moderate network load conditions., (© 2024. The Author(s).)

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is associated with altered gut microbiota; however, there has been a focus on fecal samples, which are not representative of the entire digestive tract. Mucosal biopsies of the descending duodenum were collected. Five regions of the 16S rRNA gene were amplified and sequenced. Other assessments conducted on the study subjects included body mass index, transient elastography, liver enzymes, and lipid profile. Fifty-one subjects (36 with MASLD and 15 controls) were evaluated. There was no significant difference between the two groups regarding alpha- or beta-diversity of the duodenal mucosal microbiota. Linear discriminant analysis effect size (LEfSe) analysis showed that the genera Serratia and Aggregatibacter were more abundant in the duodenal mucosa of patients with MASLD, whereas the duodenal mucosal microbiota of the healthy controls was enriched with the genus Petrobacter. PICRUSt2 analysis revealed that genes associated with amino acid degradation and carboxylate degradation were significantly enriched in the duodenal mucosal microbiota of patients with MASLD. Our findings reveal the duodenal mucosal microbiota in patients with MASLD, which could contribute to future studies investigating the causal relationship between duodenal microbiota and MASLD., (© 2024. The Author(s).)

The use of titanium implants as fixed supports following fractures in patients with OP can often result in sterile loosening and poor osseointegration. Oxidative stress has been shown to play a particularly important role in this process. While TSA has been reported to facilitate in vivo osteogenesis, the underlying mechanisms remain to be clarified. It also remains unclear whether TSA can improve the osseointegration of titanium implants. This study investigated whether TSA could enhance the osseointegration of titanium rods by activating AKT/Nrf2 pathway signaling, thereby suppressing oxidative stress. MC3T3-E1 cells treated with CCCP to induce oxidative stress served as an in vitro model, while an OVX-induced OP rat model was employed for in vivo analysis of titanium rod implantation. In vitro, TSA treatment of CCCP-treated MC3T3-E1 cells resulted in the upregulation of osteogenic proteins together with increased AKT, total Nrf2, nuclear Nrf2, HO-1, and NQO1 expression, enhanced mitochondrial functionality, and decreased oxidative damage. Notably, the PI3K/AKT inhibitor LY294002 reversed these effects. In vivo, TSA effectively enhanced the microstructural characteristics of distal femur trabecular bone, increased BMSCs mineralization capacity, promoted bone formation, and improved the binding of titanium implants to the surrounding tissue. Finally, our results showed that TSA could reverse oxidative stress-induced cell damage while promoting bone healing and improving titanium rods' osseointegration through AKT/Nrf2 pathway activation., (© 2023. The Author(s).)

Necroptosis is a recently discovered apoptotic mechanism that has been linked to tumor formation, prognosis, and treatment response. However, the relationship between the TME and NRGs remains unclear. In this study, we analyzed the expression patterns of NRGs in 769 HNSCC cases from two distinct data sets. Our findings revealed distinct genetic groups and a correlation between patient clinical features, prognosis, TME cell infiltration characteristics, and NRG alterations. We then developed an NRG model to predict OS and confirmed its accuracy in predicting OS in HNSCC patients. Moreover, we have devised a precise nomogram that enhances the clinical utility of the NRG model substantially. The low-risk group had a better OS, and they were associated with immune suppression, more mutated genes, and higher TIDE scores. The risk score also had a significant correlation with the CSC index and susceptibility to anti-tumor agents. Our study provides insights into how NRGs affect prognosis, clinically significant features, TME, and immunotherapy response in HNSCC. With a better knowledge of NRGs in HNSCC, we could assess the prognosis and develop immunotherapy regimens that are more successful at opening up new doors., (© 2023. The Author(s).)

Human epidermal growth factor receptor 2 (HER2) gene amplification helps identify breast cancer patients who may respond to targeted anti-HER2 therapy. This study aims to develop an automated method for quantifying HER2 fluorescence in situ hybridization (FISH) signals and improve the working efficiency of pathologists. An Aitrox artificial intelligence (AI) model based on deep learning was constructed, and a comparison between the AI model and traditional manual counting was performed. In total, 918 FISH images from 320 consecutive invasive breast cancers were analysed and automatically classified into 5 groups according to the 2018 ASCO/CAP guidelines. The overall classification accuracy was 85.33% (157/184) with a mean average precision of 0.735. In Group 5, the most common group, the consistency was as high as 95.90% (117/122), while the consistency was low in the other groups due to the limited number of cases. The causes of this inconsistency, including clustered HER2 signals, coarse CEP17 signals and some section quality problems, were analysed. The developed AI model is a reliable tool for evaluating HER2 amplification statuses, especially for breast cancer in Group 5; additional cases from multiple centres could further improve the accuracy achieved for other groups., (© 2023. The Author(s).)

The detection precision of infrared seeker directly affects the guidance precision of infrared guidance system. To solve the problem of low target detection accuracy caused by the change of imaging scale, complex ground background and inconspicuous infrared target characteristics when infrared image seeker detects ground tank targets. In this paper, a You Only Look Once, Transform Head Squeeze-and-Excitation (YOLOv5s-THSE) model is proposed based on the YOLOv5s model. A multi-head attention mechanism is added to the backbone and neck of the network, and deeper target features are extracted using the multi-head attention mechanism. The Cross Stage Partial, Squeeze-and-Exclusion module is added to the neck of the network to suppress the complex background and make the model pay more attention to the target. A small object detection head is introduced into the head of the network, and the CIoU loss function is used in the model to improve the detection accuracy of small objects and obtain more stable training regression. Through these several improvement measures, the background of the infrared target is suppressed, and the detection ability of infrared tank targets is improved. Experiments on infrared tank target datasets show that our proposed model can effectively improve the detection performance of infrared tank targets under ground background compared with existing methods, such as YOLOv5s, YOLOv5s + SE, and YOLOV 5 s + Convective Block Attention Module., (© 2023. The Author(s).)

Mobile pastoralism was a key lifeway in the Late Bronze and Iron Age of Northwest China and played a crucial role in the regional socio-cultural development, as well as the formation of transregional networks. In this paper we analyse the complete faunal assemblage from House F2 in Shirenzigou, on the Eastern Tianshan Mountains, in combination with radiocarbon dating and spatial analysis, to explore local animal resources exploitation strategies and related socio-economic implications. Our results show an intensive multipurpose caprine management, while the exploitation of other domestic taxa, cattle, horses and dogs, was limited. This pastoral economy was supplemented with some hunting. The differentiated use of space in F2 indicates that basic domestic tasks were carried out in the structure, however its position within the landscape and the predominance of bone tools related to warfare and socialization activities, suggests that it was not an ordinary dwelling, it may also have served as a watch post for the summer encampment within the gully. Our findings constitute an important contribution on the discussion on animal resources exploitation strategies and their relationship with evolving socio-economic complexity in the Eastern Tianshan region in the late first millennium BCE., (© 2023. The Author(s).)

In present study, sodium salt of α-naphthalene acetic acid (NA), potassium salt of fulvic acid (KF) and their combinations were applied to the growth substrates of tomato seedlings (Solanum lycopersicum L.) under chilling stress. The changes in aboveground biomass, root attributes, pigment contents, chlorophyll fluorescence, photosynthesis, osmotic regulation substances, and antioxidant enzymes activity of the tomato seedlings in response to NA and KF were investigated. The application of NA, KF and their combination could promote the growth of plant height and stem diameter of tomato seedlings under chilling stress to varying degrees, and improve root characteristics by increasing root volume, root length and root activity, and increase dry matter accumulation. In addition, the combined use of NA and KF improved the seedling leaf chlorophyll content, qP, Fv/Fm, ΦPSII , Pn and increased the activity of antioxidant enzymes in the tomato plants. The above results suggested a synergistic effect between NA and KF to stimulate the seedlings growth and to enhance the ROS scavenging ability of tomato, which has never been reported in previous research before. However, further researches are needed to explore the physiological and molecular mechanism underlying the synergistic effect between NA and KF., (© 2023. The Author(s).)

Magnolia sinostellata is one of the endangered species in China and largely suffers light deficiency stress in the understory of forest. However, the weak light response molecular mechanism remains unclear. More importantly, hub genes in the molecular network have not been pinpointed. To explore potential regulators in the mechanism, weighted gene co-expression network analysis (WGCNA) was performed to analysis the trancriptome data of M. sinostellata leaves subjected to weak light with different time points. Gene co-expression analysis illustrated that module 1, 2 and 3 were closely associated with light deficiency treatment, which. Gene ontology and KEGG analyses showed that genes in module 1 mainly participated in amino and nucleotide metabolism, module 2 mostly involved in carbon fixation and module 3 mostly regulated photosynthesis related pathways, among which 6, 7 and 8 hub genes were identified, respectively. Hub genes isoform&#95;107196 in module 1 and isoform&#95;55976 in module 2 were unique to M. sinostellata. This study found that light deficiency inhibited photosynthesis and stress tolerance, while improved carbon metabolism and flowering related pathways in M. sinostellata, which can impact its accumulation reserves of growth and reproduction in the next season. In addition, key shade response regulators identified in this study have laid a firm foundation for further investigation of shade response molecular mechanism and protection of other shade sensitive plants., (© 2022. The Author(s).)

Lagovirus europaeus GI.1 belongs to Lagovirus in the Caliciviridae family. GI.1 causes an acute, septic, and highly lethal disease in rabbits. Lagovirus europaeus GI.2, a new variant of GI.1, has caused explosive mortality in rabbits of all ages in Sichuan Province, China. To explore the differences in pathogenicity of rabbits infected with GI.1/GI.2, we investigated the virulence and disease progression of a naturally occurring GI.1/GI.2 in 4-week-old, 13-week-old, and 25-week-old New Zealand White laboratory rabbits after GI.1/GI.2 infection. Objective measures of disease progression were recorded using continuous body-temperature monitoring. We observed the kittens were infected with GI.2 during the most urgent course of the disease, and GI.1 was not lethal to kittens. We found that the target organ of both GI.1 and GI.2 was the liver, but the disease course of the two viruses was differed. Our study enriches the research on the pathogenicity of GI.1 and GI.2 under the same conditions., (© 2022. The Author(s).)

This paper presents a microwave microfluidic biosensor for monitoring blood glucose levels. The glucose sensor is a triple ring microstrip patch antenna integrated with a biomimetic microfluidic device capable of measuring a fixed volume of glucose solution. The sensor was utilized to detect 50-500 mg/dL glucose solutions. The interaction of the glucose solution with the electromagnetic field on the patch's surface influences both the resonance frequency and the magnitude of reflection coefficient. The results indicate that the microfluidic device can reduce experimental error and enhance the correlation between glucose concentration, resonant frequency, and reflection coefficient. Finally, the microfluidic sensor had a sensitivity of 0.25 MHz/(mg/dL), a detection limit as low as 7.7 mg/dL, and correlation coefficients of resonance frequency and reflection coefficient with a glucose concentration of 0.996 and 0.984, respectively. The experiment on the sensor's stability verifies the sensor's excellent stability and rapid response (~ 150 ms). Consequently, the device can be used to differentiate the concentration of glucose solutions, as well as to detect blood glucose levels at an early stage., (© 2022. The Author(s).)

Transgenic technology played a crucial role in developing insect-resistant plants resulting in the reduced application of pesticides. This article reports the expression of two cry proteins (Cry3Bb1 and Cry3) in cotton for enhanced resistance against chewing insect pests. The aforementioned genes were synthetically developed and were cloned under appropriate regulatory sequences followed by transformation into Eagle-2 genotype (Gossypium hirsutum) of cotton through shoot apex-cut Agro-infiltration. The transgene integration was validated by polymerase chain reaction using primers flanking the aforementioned cry genes. Transgene expression was assessed by qRT-PCR using GADPH as a reference gene. The relative fold expression analyses revealed the highest expression of the transgene(s) in M1 plants, which is a 4.5-fold expression (Cry3 + Cry3Bb1) followed by M3 (fold expression, 3.0) (Cry3Bb1) and M2 (fold expression, 2.5) (Cry3) transformants of cotton. The confirmed transgenic plants were exposed to insect pests, pink bollworm (Pectinophora gossypiella), and army bollworm (Helicoverpa armigera). Bioassay results revealed that 60% mortality was observed against pink bollworm, and 75% mortality was observed against army bollworm in transgenic plants containing both Cry3Bb1 and Cry3 genes (M1 transgenic plants). In M2 transgenic plants containing only the Cry3Bb1 gene, the mortality was observed to be 40% in the pink bollworm population, whereas 45% mortality was observed in the army bollworm population. In the case of M3 transgenic plants containing single gene-Cry3, the mortality was 20% in the pink bollworm population, whereas 30% mortality was observed in the army bollworm population. Almost no mortality was observed in non-transgenic Eagle-2 control plants. Hence, the developed cotton transformants have improved resistance against chewing insect pests., (© 2022. The Author(s).)

We compared the efficacy and safety of ultrasound (US)-guided radiofrequency ablation (RFA) and parathyroidectomy (PTX) for the treatment of secondary hyperparathyroidism (SHPT). In this single-center retrospective study, we divided patients into PTX (n = 53) and RFA (n = 47) groups. The primary outcome was the proportion of patients who achieved the target intact parathyroid hormone (iPTH) concentration range (≤ 300 pg/mL). Secondary outcomes were the differences in the changes in iPTH, calcium, and phosphorus levels over time and prognosis. iPTH concentrations of 82.1% and 64.1% in the PTX and RFA groups, respectively, were within the recommended range at the endpoint (P = 0.07). iPTH concentrations in the PTX and RFA groups dropped sharply after treatment (82 ± 163 pg/mL and 280 ± 307 pg/mL, respectively, P < 0.001). There was no difference in the trends of iPTH, calcium, and phosphorus levels between the two groups (P > 0.05). Survival analysis revealed no differences in all-cause mortality and cumulative response rate between the two groups (P = 0.90, P = 0.14, respectively). Notably, the incidence of infection and length of the hospital stay in the RFA group were significantly lower. The preoperative bone-specific alkaline phosphatase concentration was a risk factor for postoperative hypocalcemia. US-guided RFA is minimally invasive and compared to PTX in terms of long-term efficacy and complications in the treatment of severe SHPT in maintenance dialysis patients. It may be used as an alternative technique to PTX; however, further studies are needed., (© 2022. The Author(s).)

To investigate the effect of radiation therapy (RT) after endometrial cancer (EC) diagnosis on the risk of occurring secondary bladder cancer (SBC) as well as on the survival outcome of those patients who suffered with SBC. Data was extracted from the Surveillance, Epidemiology, and End Results database between 1973 and 2015. Chi-squared test was utilized to compare clinicopathological characteristics among different groups. The Fine and Gray's competing risk model was utilized to assess cumulative incidence and risk of occurring SBC in EC survivors. The Kaplan-Meier method and the Cox regression model were used for survival analysis. As a result, a total of 108,060 EC patients were included, among which 37,118 (34.3%) patients received RT while others did not. The incidence of SBC was 1.31%, 1.76% and 0.96% among patients who received prior brachytherapy, external-beam radiotherapy (EBRT) and others, respectively. Both of the EBRT (standardized incidence ratio (SIR) = 2.24, 95% CI [1.94-2.58]) and brachytherapy (SIR = 1.76, 95% CI [1.44-2.13]) group had a higher incidence of SBC than the general population in USA. The competing risk analysis demonstrated that receiving EBRT (HR = 1.97, 95% CI [1.64-2.36]) or brachytherapy (HR = 1.46, 95% CI [1.14-1.87]) were all independent risk factors for developing SBC. A survival detriment was only observed in SBC patients who received prior EBRT after EC diagnosis, but not for brachytherapy, when compared with those who did not undergo RT. Additionally, there were no significant survival differences between primary bladder cancer and SBC with or without prior RT history. Patients who underwent RT after EC had an increased risk of developing bladder cancer as secondary primary cancer. The prognosis of these SBC patients varied depending on types of RT that received after EC diagnosis., (© 2022. The Author(s).)

A 75-day rearing trial was designed to study the response of juvenile Megalobrama amblycephala to dietary methionine (Met) levels. Three practical diets with graded Met levels (0.40%, 0.84% and 1.28% dry matter) were prepared to feed the juvenile fish. The results showed that the 0.84% Met diet significantly improved the growth compared with 0.40% diets. Compared with 0.84% and 1.28% Met, 0.40% Met significantly increased the hepatic lipid content, while decreasing the muscular lipid and glycogen contents. 0.40% Met decreased the protein levels of phospho-Eukaryotic initiation factor 4E binding protein-1 (p-4e-bp1), 4e-bp1 and Ribosomal protein S6 kinase 1 in the liver, compared with 0.84% diet, while an increasing trend was observed in the muscle. Met supplementation tended to decrease and increase lipid synthesis in the liver and muscle, respectively, via changing mRNA levels of sterol regulatory element-binding protein 1, fatty acid synthetase and acetyl-CoA carboxylase. 1.28% dietary Met promoted fatty acid β-oxidation and lipolysis in both the liver and muscle by increasing carnitine palmitoyl transferase 1, peroxisome proliferator activated receptor alpha, lipoprotein lipase and lipase mRNA levels. Compared with 0.40% and 0.84% dietary Met, 1.28% Met enhanced the mRNA levels of hepatic gluconeogenesis related genes phosphoenolpyruvate carboxykinase (pepck), and glucose-6-phosphatase, and muscular glycolysis related genes phosphofructokinase (pfk), and pyruvate kinase (pk). The mRNA levels of hepatic pfk, pk and glucokinase were markedly downregulated by 1.28% Met compared with 0.84% level. Muscular pepck, glycogen synthase, and hepatic glucose transporters 2 mRNA levels were induced by 1.28% Met. Generally, deficient Met level decreased the growth of juvenile Megalobrama amblycephala, and the different nutrient metabolism responses to dietary Met were revealed in the liver and muscle., (© 2021. The Author(s).)

The prevalence of coronary artery disease (CAD) in Tibetan Highlanders is lower than that in plain-living individuals, but the mechanism still unclear. Gut microbiota (GM) disorder is considered one of the potential factors involved in the pathogenesis of CAD, but the GM characteristics of Tibetan Highlanders suffering from CAD are unknown. We sequenced the V3-V4 region of the 16S ribosomal RNA of gut bacteria from fecal samples from Tibetan and Han CAD patients and healthy individuals inhabiting the Qinghai-Tibet Plateau, as well as from Han CAD patients and healthy individuals living at sea level, and we analyzed the GM characteristics of these subjects by bioinformatics analysis. The results showed that Tibetan Highlanders suffering from CAD had higher GM α-diversity, with differently distributed cluster compared with healthy Tibetan Highlanders and Han CAD patients living at high and low altitudes. Genera Catenibacterium, Clostridium&#95;sensu&#95;stricto, Holdemanella, and Ruminococcus 2 were enriched in Tibetan Highlanders suffering from CAD compared with healthy Tibetan Highlanders and Han CAD patients living at high- and low-altitudes. Prevotella was enriched in Tibetan Highlanders suffering from CAD compared with Han CAD patients living at high- and low-altitudes. Moreover, Catenibacterium was positively correlated with Prevotella. Additionally, Catenibacterium, Holdemanella, and Prevotella were positively correlated with fermented dairy product, carbohydrate and fiber intake by the subjects, while Clostridium&#95;sensu&#95;stricto was negatively correlated with protein intake by the subjects. In conclusion, our study indicated that Tibetan Highlanders suffering from CAD showed distinct GM, which was linked to their unique dietary characteristics and might associated with CAD., (© 2021. The Author(s).)

Fish has poor utilization capacity for glucose metabolism. The possible reasons are related to the core regulatory elements of glucose metabolism: transport proteins. Studies on the species and functions of Sglt1 in aquatic animals are scarce, therefore further studies are needed. In this study, the full length of blunt snout bream (Megalobrama amblycephala) sglt1 (Masglt1) was 2965 bp including 5'-UTR region of 168 bp and a 3'-UTR region of 820 bp. Masglt1 have a highest sequence homology in Cypriniformes fish. MaSglt1 protein was identified as a transmembrane protein with 14 α-helix structures locating plasma membrane by the methods of predicted tertiary structure and immunohistochemical staining. MaSglt1 protein has a hollow channel forms which could be specifically coupled with two Na + ions to recognize glucose and carry out transmembrane transport. High sglt1 mRNA was found in the intestine and kidney. The mRNA levels of intestinal sglt1 had a positive correlation with dietary starch levels at 3 h after feeding, and the mRNA was significantly higher than that at 24 h, however, the mRNA levels of renal sglt1 presented results opposite to those of intestinal sglt1. The mRNA levels of renal sglt1 had a positive correlation with dietary starch levels at 24 h after feeding, and the expression was significantly higher than that at 3 h. These results confirmed that Masglt11 was mainly found in the intestine and kidney and was located in the cell membrane, playing a role in glucose homeostasis.

Phytophthora nicotianae is highly pathogenic to Solanaceous crops and is a major problem in tobacco production. The tobacco cultivar Beihart1000-1 (BH) is resistant, whereas the Xiaohuangjin 1025 (XHJ) cultivar is susceptible to infection. Here, BH and XHJ were used as models to identify resistant and susceptible genes using RNA sequencing (RNA-seq). Roots were sampled at 0, 6, 12, 24, and 60 h post infection. In total, 23,753 and 25,187 differentially expressed genes (DEGs) were identified in BH and XHJ, respectively. By mapping upregulated DEGs to the KEGG database, changes of the rich factor of "plant pathogen interaction pathway" were corresponded to the infection process. Of all the DEGs in this pathway, 38 were specifically regulated in BH. These genes included 11 disease-resistance proteins, 3 pathogenesis-related proteins, 4 RLP/RLKs, 2 CNGCs, 7 calcium-dependent protein kinases, 4 calcium-binding proteins, 1 mitogen-activated protein kinase kinase, 1 protein EDS1L, 2 WRKY transcription factors, 1 mannosyltransferase, and 1 calmodulin-like protein. By combining the analysis of reported susceptible (S) gene homologs and DEGs in XHJ, 9 S gene homologs were identified, which included 1 calmodulin-binding transcription activator, 1 cyclic nucleotide-gated ion channel, 1 protein trichome birefringence-like protein, 1 plant UBX domain-containing protein, 1 ADP-ribosylation factor GTPase-activating protein, 2 callose synthases, and 2 cellulose synthase A catalytic subunits. qRT-PCR was used to validate the RNA-seq data. The comprehensive transcriptome dataset described here, including candidate resistant and susceptible genes, will provide a valuable resource for breeding tobacco plants resistant to P. nicotianae infections.

The nucleosome is the basic structural repeating unit of chromatin. DNA damage and cell apoptosis release nucleosomes into the blood circulatory system, and increased levels of circulating nucleosomes have been observed to be related to inflammation and autoimmune diseases. However, how circulating nucleosomes trigger immune responses has not been fully elucidated. cGAS (cGMP-AMP synthase) is a recently discovered pattern recognition receptor that senses cytoplasmic double-stranded DNA (dsDNA). In this study, we employed in vitro reconstituted nucleosomes to examine whether extracellular nucleosomes can gain access to the cytoplasm of mammalian cells to induce immune responses by activating cGAS. We showed that nucleosomes can be taken up by various mammalian cells. Additionally, we found that in vitro reconstituted mononucleosomes and oligonucleosomes can be recognized by cGAS. Compared to dsDNA, nucleosomes exhibit higher binding affinities to cGAS but considerably lower potency in cGAS activation. Incubation of monocytic cells with reconstituted nucleosomes leads to limited production of type I interferons and proinflammatory cytokines via a cGAS-dependent mechanism. This proof-of-concept study reveals the cGAS-dependent immunogenicity of nucleosomes and highlights the potential roles of circulating nucleosomes in autoimmune diseases, inflammation, and antitumour immunity.

Hepatocellular carcinoma (HCC) is a common malignant tumor in China. In the present study, we aimed to construct and verify a prediction model of recurrence in HCC patients using databases (TCGA, AMC and Inserm) and machine learning methods and obtain the gene signature that could predict early relapse of HCC. Statistical methods, such as feature selection, survival analysis and Chi-Square test in R software, were used to analyze and select mutant genes related to disease free survival (DFS), race and vascular invasion. In addition, whole-exome sequencing was performed on 10 HCC patients recruited from our center, and the sequencing results were compared with the databases. Using the databases and machine learning methods, the prediction model of recurrence was constructed and optimized, and the selected mutant genes were verified in the test group. The accuracy of prediction was 74.19%. Moreover, these 10 patients from our center were used to verify these mutant genes and the prediction model, and a success rate of 80% was achieved. Collectively, we discovered recurrence-related genes and established recurrence prediction model of recurrence for HCC patients, which could provide significant guidance for clinical prediction of recurrence.

Plasma trimethylamine N-oxide (TMAO) is associated with coronary atherosclerotic plaque and cardiovascular disease risk, but associations between gut microbes in acute coronary syndrome (ACS) and post-ST-segment elevation myocardial infarction (post-STEMI) events are unknown. We investigated associations between gut microbial taxa and systemic TMAO levels and the possible TMAO contribution to incident post-STEMI cardiovascular events., Patients and Methods: A total of 60 patients, including 30 with unstable angina pectoris (UAP), 30 post-STEMI and 30 healthy controls, were enrolled from June to November 2017. Metagenomic sequencing was performed and TMAO and IL-6 were detected., Results: Minimal discriminators of gut microbial taxa (top 40) distinguished ACS patients from controls. Serum TMAO levels were positively associated with increased abundance of Aerococcaceae, Ruminococcaceae&#95;UCG.005, Ruminococcaceae&#95;UCC.014 and X. Eubacterium&#95;fissicatena, and decreased abundance of Lachnospiraceae&#95;FCS020 (P < 0.05). Elevated serum TMAO levels correlated independently with ACS (P < 0.05). Risk stratification for incident major adverse cardiovascular events (MACE) improved at one year in patients with serum TMAO levels ≦2.19 µM. Serum interleukin-6 levels were not significantly increased in patients with ACS and post-STEMI MACE., Conclusions: ACS and incident post-STEMI MACE may be associated with the gut bacteria choline metabolite TMAO. The specific gut microbial taxa identified in association with serum TMAO levels may be potential predictive biomarkers for accurate diagnosis of ACS onset.

Long noncoding RNAs (lncRNAs) are critical gene expression regulators and are involved in several bone diseases. To explore the potential roles of lncRNAs in osteonecrosis of the femoral head (ONFH), we investigated for the first time the lncRNA expression profile of bone marrow mesenchymal stem cells (BMSCs) from patients with steroid-induced ONFH (SONFH) with microarray and bioinformatics analysis. A total of 1878 lncRNAs and 838 mRNAs were significantly up-regulated while 1842 lncRNAs and 1937 mRNAs were statistically down-regulated in the SONFH group compared with control group. The results validated by qRT-PCR were consistent with the microarray profiling data, especially involved in upregulation and downregulation of critical lncRNAs as well as mRNAs expression related to adipogenic and osteogenic differentiation. Pathway analyses revealed 40 signaling pathways with significant differences, especially the signaling pathways to regulate stem cell pluripotency. The CNC and ceRNA network indicated that lncRNA RP1-193H18.2, MALAT1 and HOTAIR were associated with abnormal osteogenic and adipogenic differentiation of BMSCs in the patients with SONFH. Our results suggest the lncRNA expression profiles were closely associated with the abnormal adipogenic and osteogenic transdifferentiation of BMSCs during the development of SONFH and explore a new insight into the molecular mechanisms of SONFH.

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.

Endothelial cell apoptosis induced by oxidative stress is an early event in the development of atherosclerosis. Several antioxidant enzymes which can cope with oxidative stress are up-regulated by the anti-atherogenic laminar blood flow often seen in straight or unbranched regions of blood vessels. However, the molecular mechanism responsible for flow-induced beneficial effects is incompletely understood. Here we report the role of glutaredoxin 1 (Grx1), an antioxidant enzyme, in flow-mediated protective effect in endothelial cells. Specifically, we found that Grx1 is markedly up-regulated by the steady laminar flow. Increasing Grx1 reduces the pro-apoptotic protein Bim expression through regulating Akt-FoxO1 signaling and also attenuates H 2 O 2 -induced Bim activation via inhibiting JNK phosphorylation, subsequently preventing the apoptosis of endothelial cells. Grx1 knockdown abolishes the inhibitory effect of steady laminar flow on Bim. The inhibitory effect of Grx1 on Bim is dependent on Grx1's thioltransferase activity. These findings indicate that Grx1 induction plays a key role in mediating the protective effect of laminar blood flow and suggest that Grx1 may be a potential therapeutic target for atherosclerosis.

Quantifying the distribution of specific neurons throughout the whole brain is crucial for understanding physiological actions, pathological alterations and pharmacological treatments. However, the precise cell number and density of specific neurons in the entire brain remain unknown because of a lack of suitable research tools. Here, we propose a pipeline to automatically acquire and analyse the brain-wide distribution of type-specific neurons in a mouse brain. We employed a Brain-wide Positioning System to collect high-throughput anatomical information with the co-localized cytoarchitecture of the whole brain at subcellular resolution and utilized the NeuroGPS algorithm to locate and count cells in the whole brain. We evaluated the data continuity of the 3D dataset and the accuracy of stereological cell counting in 3D. To apply this pipeline, we acquired and quantified the brain-wide distributions and somatic morphology of somatostatin-expressing neurons in transgenic mouse brains. The results indicated that this whole-brain cell counting pipeline has the potential to become a routine tool for cell type neuroscience studies.

This study observed the efficacy and safety of JinqiJiangtang tablets (JQJT tablets, a traditional Chinese patent medicine) for pre-diabetes. Four hundred patients with pre-diabetes at five centres were treated for 12months and followed for an additional 12months to investigate the preventative effects of JQJT tablets (Registration ID: ChiCTR-PRC-09000401). The incidence rate of diabetes mellitus was the primary endpoint. The risk of converting from pre-diabetes to diabetes was 0.58-fold less in the JQJT tablets group than in the placebo group [HR (95% CI): 0.58 (0.384, 0.876), P = 0.010]. Furthermore, the probability of achieving normalized blood glucose was 1.41-fold greater in the JQJT tablets group than in the placebo group [HR (95% CI): 1.41 (1.002, 1.996), P = 0.0049]. ITT analysis revealed that the incidence of diabetes upon treatment completion was 16.5% in the JQJT tablets group compared with 28.9% in the control group. The percentage of patients with normalized blood glucose upon 12-month intervention was 41.8% in the JQJT tablets group compared with 27.8% in the control group. JQJT tablets could be an effective intervention for preventative treatment of Type 2 diabetes mellitus.

Deregulated activity of Ras GTPases has been observed in many types of human cancers, and contributes to the diverse aspects of carcinogenesis. Although the significance in tumorigenesis has been widely accepted and many therapeutic drugs are under development, little attention has been dedicated to the development of sensors for the Ras activity in vivo. Therefore, based on the split firefly luciferase complementation strategy, we developed a monomolecular bioluminescent biosensor to image endogenous Ras activity in living subject. In this biosensor, two inactive luciferase fragments are sandwiched by Raf-1, whose conformation changes upon GTP-Ras binding. Thus, the Ras activity can be surrogated by the intensity of the complementary luciferase. The bioluminescence analyses demonstrated that this novel biosensor behaved the robust and sensitive reporting efficiency in response to the dynamical changes of Ras activity, both in living colorectal cancer cells and in vivo. Compared to the traditional method, such as the pull-down assay, the bioluminescent sensor is simply, noninvasive, faster and more sensitive for the analysis of the endogenous Ras activity. This innovative work opens up the way for monitoring the preclinical curative effect and high-throughput screening of therapeutic drugs targeting Ras pathways.

This study evaluated the mechanisms governing insulin resistance, glucose metabolism and lipogenesis in juvenile fish fed with graded levels of dietary arginine. The results showed that, compared with the control group (0.87%), 2.31% dietary arginine level resulted in the upregulation of the relative gene expression of IRS-1, PI3K and Akt in the insulin signaling pathway, while 2.70% dietary arginine level led to inhibition of these genes. 1.62% dietary arginine level upregulated glycolysis by increasing GK mRNA level; 2.70% dietary arginine level upregulated gluconeogenesis and resulted in high plasma glucose content by increasing PEPCK and G6P mRNA level. Furthermore, 2.70% dietary arginine level significantly lowered GLUT2 and increased PK mRNA levels. 1.62% dietary arginine level significantly upregulated ACC, FAS and G6PDH mRNA levels in the fat synthesis pathway and resulted in high plasma TG content. These results indicate that 1.62% dietary arginine level improves glycolysis and fatty acid synthesis in juvenile blunt snout bream. However, 2.70% dietary arginine level results in high plasma glucose, which could lead to negative feedback of insulin resistance, including inhibition of IRS-1 mRNA levels and activation of gluconeogenesis-related gene expression. This mechanism seems to be different from mammals at the molecular level.

Whether inhibition is a unitary or multifaceted construct is still an open question. To clarify the electrophysiological distinction among the different types of inhibition, we used a modified flanker paradigm, in which interference inhibition, rule inhibition, and response inhibition were compared to non-inhibition condition. The results indicated that, compared to the non-inhibition condition (1) the interference inhibition condition induced larger negativities during N2 epoch at the frontal region, (2) the rule inhibition condition elicited a larger N1 at the posterior region, followed by a larger P3a at the frontal region, reflecting the function of proactive cognitive control in the new stimulus-reaction (S-R) association, and (3) the response inhibition condition evoked a larger P3b at the posterior region, reflecting the process of suppressing the old response and reprogramming the new action. These findings provide new evidence that distinct neural mechanisms underlie different types of inhibition.

Corticofugal projection neurons are key components in connecting the neocortex and the subcortical regions. In the barrel field, these neurons have various projection targets and play crucial roles in the rodent whisker sensorimotor system. However, the projection features of corticofugal projection neurons at the single-axon level are far from comprehensive elucidation. Based on a brain-wide positioning system with high-resolution imaging for Thy1-GFP M-line mice brains, we reconstructed and analyzed more than one hundred corticofugal projection neurons in both layer V and VI of barrel cortex. The dual-color imaging made it possible to locate the neurons' somata, trace their corresponding dendrites and axons and then distinguish the neurons as L5 type I/II or L6 type. The corticofugal projection pattern showed significant diversity across individual neurons. Usually, the L5 type I neurons have greater multi-region projection potential. The thalamus and the midbrain are the most frequent projection targets among the investigated multidirectional projection neurons, and the hypothalamus is particularly unique in that it only appears in multidirectional projection situations. Statistically, the average branch length of apical dendrites in multi-region projection groups is larger than that of single-region projection groups. This study demonstrated a single-axon-level analysis for barrel corticofugal projection neurons, which could provide a micro-anatomical basis for interpreting whisker sensorimotor circuit function.

Oxidative stress is the major cause of skin aging that includes wrinkles, pigmentation, and weakened wound healing ability. Application of antioxidants in skin care is well accepted as an effective approach to delay the skin aging process. Methylene blue (MB), a traditional mitochondrial-targeting antioxidant, showed a potent ROS scavenging efficacy in cultured human skin fibroblasts derived from healthy donors and from patients with progeria, a genetic premature aging disease. In comparison with other widely used general and mitochondrial-targeting antioxidants, we found that MB was more effective in stimulating skin fibroblast proliferation and delaying cellular senescence. The skin irritation test, performed on an in vitro reconstructed 3D human skin model, indicated that MB was safe for long-term use, and did not cause irritation even at high concentrations. Application of MB to this 3D skin model further demonstrated that MB improved skin viability, promoted wound healing and increased skin hydration and dermis thickness. Gene expression analysis showed that MB treatment altered the expression of a subset of extracellular matrix proteins in the skin, including upregulation of elastin and collagen 2A1, two essential components for healthy skin. Altogether, our study suggests that MB has a great potential for skin care.

A novel turn-on two-photon fluorescent probe NS-N 2 H 4 was developed with the 2-benzothiazoleacetonitrile as a new recognition site for the detection of hydrazine (N 2 H 4 ). The two-photon probe exhibited favorable properties including high selectivity, low cytotoxicity and almost 16-fold fluorescence enhancement in the presence of N 2 H 4 in solution. The probe could be used to image hydrazine in the living cells. Notably, we also used the two-photon fluorescent probe to image hydrazine in the tissue imaging for the first time. Furthermore, by the way of probe-loaded TLC plate, we further monitored vapor of hydrazine. Therefore, the novel two-photon probe is expected to be employed to detect N 2 H 4 in biosamples and environmental pollution and the new recognition site will be widely applied to construct fluorescent probes for the detection of N 2 H 4 .

Spectral resolving and imaging surface plasmon modes in noble metal nanostructures are important for applications in nanophotonics. Here, we use cathodoluminescence (CL) spectroscopy to excite and probe quasi-dark plasmon modes of Au nanoring cavities. Numerical simulations of both the spectra and the electromagnetic field distribution are carried out by using boundary element method. Good agreement between the experimental and simulated results is obtained. Particularly, CL is shown as an efficient method to probe quadrupole modes, which is difficult for traditional optical means. Moreover, a high Purcell factor in excess of 100 is obtained for the dark quadrupole modes in gold ring cavities. Our work provides an efficient way to explore the initial nature of surface plasmon modes in metal nanostructures.

Although clustering of genes from the same metabolic pathway is a widespread phenomenon, the evolution of the polysaccharide biosynthetic gene cluster remains poorly understood. To determine the evolution of this pathway, we identified a scattered production pathway of the polysaccharide sanxan by Sphingomonas sanxanigenens NX02, and compared the distribution of genes between sphingan-producing and other Sphingomonadaceae strains. This allowed us to determine how the scattered sanxan pathway developed, and how the polysaccharide gene cluster evolved. Our findings suggested that the evolution of microbial polysaccharide biosynthesis gene clusters is a lengthy cyclic process comprising cluster 1 → scatter → cluster 2. The sanxan biosynthetic pathway proved the existence of a dispersive process. We also report the complete genome sequence of NX02, in which we identified many unstable genetic elements and powerful secretion systems. Furthermore, nine enzymes for the formation of activated precursors, four glycosyltransferases, four acyltransferases, and four polymerization and export proteins were identified. These genes were scattered in the NX02 genome, and the positive regulator SpnA of sphingans synthesis could not regulate sanxan production. Finally, we concluded that the evolution of the sanxan pathway was independent. NX02 evolved naturally as a polysaccharide producing strain over a long-time evolution involving gene acquisitions and adaptive mutations.

Target of rapamycin (TOR) acts as an important regulator of cell growth, development and stress responses in most examined diploid eukaryotes. However, little is known about TOR in tetraploid species such as cotton. Here, we show that TORC1-S6K-RPS6, the major signaling components, are conserved and further expanded in cotton genome. Though the cotton seedlings are insensitive to rapamycin, AZD8055, the second-generation inhibitor of TOR, can significantly suppress the growth in cotton. Global transcriptome analysis revealed that genes associated with jasmonic acid (JA) biosynthesis and transduction were significantly altered in AZD8055 treated cotton seedlings, suggesting the potential crosstalk between TOR and JA signaling. Pharmacological and genetic approaches have been employed to get further insights into the molecular mechanism of the crosstalk between TOR and JA. Combination of AZD8055 with methyl jasmonate can synergistically inhibit cotton growth, and additionally JA levels were significantly increased when cotton seedlings were subjected to AZD8055. JA biosynthetic and signaling mutants including jar1, coi1-2 and myc2-2 displayed TOR inhibitor-resistant phenotypes, whereas COI1 overexpression transgenic lines and jaz10 exhibited sensitivity to AZD8055. Consistently, cotton JAZ can partially rescue TOR-suppressed phenotypes in Arabidopsis. These evidences revealed that the crosstalk between TOR and JA pathway operates in cotton and Arabidopsis.

Metformin, an anti-diabetic drug commonly used for type 2 diabetes therapy, is associated with anti-angiogenic effects in conditions beyond diabetes. miR-21 has been reported to be involved in the process of angiogenesis. However, the precise regulatory mechanisms by which the metformin-induced endothelial suppression and its effects on miR-21-dependent pathways are still unclear. Bioinformatic analysis and identification of miR-21 and its targets and their effects on metformin-induced antiangiogenic activity were assessed using luciferase assays, quantitative real-time PCR, western blots, scratch assays, CCK-8 assays and tubule formation assays. In this study, miR-21 was strikingly downregulated by metformin in a time- and dose-dependent manner. miR-21 directly targeted the 3'-UTR of PTEN and SMAD7, and negatively regulated their expression. Overexpression of miR-21 abrogated the metformin-mediated inhibition of endothelial cells proliferation, migration, tubule formation and the TGF-β-induced AKT, SMAD- and ERK-dependent phosphorylations, and conversely, down-regulation of miR-21 aggravated metformin's action and revealed significant promotion effects. Our study broadens our understanding of the regulatory mechanism of miR-21 mediating metformin-induced anti-angiogenic effects, providing important implications regarding the design of novel miRNA-based therapeutic strategies against angiogenesis.

The target of Rapamycin (TOR) present in all eukaryotes is a multifunctional protein, regulating growth, development, protein translation, ribosome biogenesis, nutrient, and energy signaling. In the present study, ectopic expression of TOR gene of Arabidopsis thaliana in a widely cultivated indica rice resulted in enhanced plant growth under water-limiting conditions conferring agronomically important water-use efficiency (WUE) trait. The AtTOR high expression lines of rice exhibited profuse tillering, increased panicle length, increased plant height, high photosynthetic efficiency, chlorophyll content and low ∆ 13 C. Δ 13 C, which is inversely related to high WUE, was as low as 17‰ in two AtTOR high expression lines. These lines were also insensitive to the ABA-mediated inhibition of seed germination. The significant upregulation of 15 stress-specific genes in high expression lines indicates their contribution to abiotic stress tolerance. The constitutive expression of AtTOR is also associated with significant transcriptional upregulation of putative TOR complex-1 components, OsRaptor and OsLST8. Glucose-mediated transcriptional activation of AtTOR gene enhanced lateral root formation. Taken together, our findings indicate that TOR, in addition to its multiple cellular functions, also plays an important role in response to abiotic stress and potentially enhances WUE and yield related attributes.

This study aimed to establish a method for the selective amplification of cell-free fetal DNA (cffDNA) in maternal plasma and preserve the integrity of DNA fragments during amplification, thereby providing a sufficient amount of cffDNA to meet the requirement of routine non-invasive prenatal testing. We amplified DNA molecules in a one-reaction system without considering their particular sequences and lengths (overall amplification) by using PCR-based enrichment. We then modified PCR conditions to verify the effect of denaturation temperature on DNA amplification on various lengths of DNA (selective overall amplification). Finally, we used an optimum temperature range to amplify cffDNA selectively. Amplification results were validated by electrophoresis and real-time quantitative PCR. Our PCR-based enrichment efficiently amplified all DNA fragments with differing lengths within a single reaction system, as well as preserving the integrity of the DNA fragments. cffDNA was significantly amplified along with the selective amplification of small fragment maternal plasma DNA in an appropriate range of denaturation temperatures. We have established a PCR-based method for the simultaneous enrichment and amplification of cffDNA in order to meet the requirements of high cffDNA quantity for routine non-invasive prenatal testing.

Few studies have compared different methods when exploring the short-term effects of air pollutants on respiratory disease mortality in Wuhan, China. This study assesses the association between air pollutants and respiratory disease mortality with both time-series and time-stratified-case-crossover designs. The generalized additive model (GAM) and the conditional logistic regression model were used to assess the short-term effects of air pollutants on respiratory disease mortality. Stratified analyses were performed by age, sex, and diseases. A 10 μg/m 3 increment in SO 2 level was associated with an increase in relative risk for all respiratory disease mortality of 2.4% and 1.9% in the case-crossover and time-series analyses in single pollutant models, respectively. Strong evidence of an association between NO 2 and daily respiratory disease mortality among men or people older than 65 years was found in the case-crossover study. There was a positive association between air pollutants and respiratory disease mortality in Wuhan, China. Both time-series and case-crossover analyses consistently reveal the association between three air pollutants and respiratory disease mortality. The estimates of association between air pollution and respiratory disease mortality from the case-crossover analysis displayed greater variation than that from the time-series analysis.

Oxidative stress is a toxicological endpoint that correlates with the nutrition status of fish through cellular damage, inflammation, and apoptosis. In order to understand the antioxidant mechanism induced by dietary emodin in Megalobrama amblycephala liver, a comparative proteomic analysis was performed to investigate the proteome alteration under emodin administration. 27 altered protein spots were separated under 30 mg kg -1 emodin stimulation based on 2-DE, and were all successfully identified using MALDI-TOF/TOF, representing 17 unique proteins. These proteins were functionally classified into antioxidant, metabolism, cytoskeleton, chaperone, signal transduction and cofactor groups. Network interaction and Gene Ontology annotation indicated 10 unique proteins were closely related to antioxidation and directly regulated by each other. Compared with the control group, administration of 30 mg kg -1 emodin significantly increased the antioxidant-related mRNA expressions of GPx1, GSTm and HSP70, but decreased the mRNA expressions of GAPDH and Sord, which was consistent with the protein expression. Nevertheless, Pgk1 and Aldh8a1 were up- and down-regulated, and ALDOB was down- and up-regulated at the mRNA and protein levels, respectively. These results revealed that the altered proteins enhanced antioxidation via complex regulatory mechanisms, and 30 mg kg -1 emodin was a suitable immunostimulant for M. amblycephala.