Search

Abstract Background While measuring meniscal extrusion quantitatively is an early risk factor for knee osteoarthritis (KOA), the biomechanics involved in this process are not well understood. This study aimed to investigate the effects of varying degrees of medial and lateral meniscal extrusion and their material softening on knee osteoarthritis progression. Methods Finite element analysis (FEA) was utilized to simulate varying degrees of meniscal extrusion (1–5 mm) in 72 knee joint models, representing progressive meniscal degeneration and material softening due to injury. Changes in von Mises stress of the cartilage and menisci and the load distribution on the tibial plateau’s meniscus and cartilage were studied under balanced standing posture in both healthy and injured knees, and statistical analysis was performed using Spearman correlation. Results Compared to healthy knees, peak stress in medial compartment tissues increased by over 40% with 4 mm of medial meniscus extrusion, and in lateral compartment tissues with 2 mm of lateral meniscus extrusion. Meniscus extrusion reduced the contact load between the meniscus and femoral cartilage but increased it between the tibial and femoral cartilages, with a maximum increase up to fivefold. Spearman correlation analysis indicated that meniscal extrusion significantly affected peak stress and contact loads in the respective knee compartment (p

IntroductionAstrocytoma is a rare tumour of the central nervous system that often manifests with non-specific clinical symptoms and lacks distinct histological features. There is a pressing need for further understanding of the clinicopathological and molecular characteristics of astrocytoma. Identifying mutant genes can aid in reliable and early diagnosis, as well as provide insights for the development of targeted therapies.MethodsThis study aims to investigate the clinicopathologic and molecular characteristics of astroblastoma. A total of four patients diagnosed with astroblastoma were included in the analysis. Clinical features, histological findings, and immunohistochemistry results were reviewed and analyzed. Genetic alterations were identified using fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS), followed by patient follow-up.ResultsThe study included four female patients, ranging in age from 8 to 44 years. One patient had a tumour in the right parietal lobe, while the other three had tumours in the spinal cord. Histology is usually characterized by pseudorosettes of astroblasts and hyalinization of blood vessels. These tumors showed a growth pattern similar to traditional intracranial astroblastoma, and the histological manifestations of the four patients were all high-grade, showing features of high-density areas of tumor cells or necrosis. Immunohistochemical staining revealed that all four patients expressed OLIG2, EMA, and vimentin, while three patients also expressed GFAP and S-100. The Ki-67 positivity index was approximately 15% in three cases and 10% in one case. Fluorescence in situ hybridization (FISH) using break-apart probes showed EWRS1 breaks in three patients and MN1 breaks in one. Further DNA or RNA-targeted biallelic sequencing identified an EWSR1(Exon1-7)-BEND2(Exon2-14) fusion in case 1, and an EWSR1(Exon1-7)-BEND2(Intergenic) fusion in case 2. In case 3, an EWSR1(Exon1-7)-NUDT10(Intergenic) fusion was present, and in case 4, an MN1(Exon1)-BEND2(Exon2) fusion was identified. The EWSR1-NUDT10 gene fusion is a new fusion type in astroblastoma. The patients were followed up for 76.5, 17.6, 33.7, and 61.3 months, respectively. Three cases experienced tumour recurrences at the spinal cord site, with multiple recurrences in case 4.DiscussionOur study unveiled the distinctive clinicopathological and molecular mutational characteristics of astrocytoma, while also identifying rare mutated genes. Additionally, the detection of MN1 or EWSR1 gene fusion through FISH or next-generation sequencing can provide valuable insights into the molecular mechanisms and aid in the differential diagnosis of astrocytoma.

Climate change and human activities have led to frequent exchanges of sedimentary and aquatic microorganisms in lakes. However, the ability of these microorganisms to survive in their respective habitats between saline lake sediment and water remains unclear. In this study, we investigated microbial sources and community composition and metabolic functions in sediments and water in Yuncheng Salt Lake using a combination of source tracking and Illumina MiSeq sequencing. The results showed that 0.10–8.47% of the microbial communities in the sediment came from the corresponding water bodies, while 0.12–10.78% of the sedimentary microorganisms contributed to the aquatic microbial populations, and the microbial contributions depended on the salinity difference between sediment and water. Habitat heterogeneity and salinity variations led to the differences in microbial diversity, community composition, and assembly between sediment and water communities. The assembly of sedimentary communities was mainly controlled by stochastic processes (>59%), whereas the assembly of aquatic communities was mainly controlled by deterministic processes (>88%). Furthermore, sediments had a higher potential for metabolic pathways related to specific biogeochemical functions than lake water. These results provide insights into the survival ability of microorganisms and the mechanisms of microbial community assembly under frequent exchange conditions in saline lakes.

Bipartite graphs are widely used for modelling various real-world scenarios characterized with binary relations, such as, scholarly articles recommendation with author-paper relations, and product recommendation with user-product relations. Particularly, maximum butterfly as a special cohesive subgraph of bipartite graphs, is playing an critical role in many promising application such as recommendation systems and research groups detection. Enumerating maximal butterfly has been proved to be a NP-hard and suffers time and space complexity. To conquer this challenge, this paper pioneers a novel problem called maximal butterfly generators search (MBGS) for facilitating the detection of maximal butterflies. The MBGS problem is to find a subgraph B of G such that maximize the number of butterflies in B and it is mathematically proved to NP-Hard. To address this problem, an equivalence relation theorem between maximum butterfly generator and maximum butterfly concept is presented. Furthermore, an effective MBGS search algorithm is proposed. Extensive experiments on real-world networks with ground-truth communities and interesting case studies validated the effectiveness and efficiency of our MBGS model and algorithm.

Abstract This work aims to explore the long‐term prognosis of hepatitis B virus‐related acute‐on‐chronic liver failure (HBV‐ACLF). In this prospective study, eligible inpatients with HBV‐ACLF are enrolled and followed up from December 2012 to February 2023, for clinical events, laboratory tests at least every 6 months. Overall, the survival rates at 28 days, 90 days, 1 year, 5 years, and 8 years are 64.7%, 48.8%, 46.1%, 43.8%, and 42.2%, respectively. Among the 8‐year mortality and liver transplant cases, ACLF survivors (who survived over 90 days) accounted for 7.8% (9/115). Among 101 patients who survived for more than 90 days, 97.9% of patients achieve virologic response at 1 year. For HBeAg‐positive patients, the HBeAg seroconversion are 25.5%, 63.6%, and 76.9% at 1, 5, and 8 years, respectively. Alanine aminotransferase, aspartate aminotransferase, total bilirubin, INR, white blood cell count, and albumin levels gradually improve within the first year. Fibrosis biomarkers APRI, FIB‐4 and Chitinase‐3‐like protein 1 (CHI3L1) levels decreases within the first 5 years. The Cox proportional hazards regression reveal that high total bilirubin (HR = 1.008, p = 0.021) is the independent risk factor for 8‐year survival of ALCF survivors. The 90‐day period following of HBV‐ACLF represented a critical juncture for long‐term prognosis, revealing favorable outcomes beyond this timeframe.

Urbanization causes immense eutrophication pressure on small urban wetlands, which play a vital role in urban ecosystems. However, our comprehension of the prolonged impacts of eutrophication on these types of wetlands continues to be significantly limited. To address this knowledge gap, we analyzed monthly physical–chemical variables and seasonal phytoplankton and zooplankton communities at the Taipa-Coloane wetland in Macau, China, from 2013 to 2019. Through the generalized additive model (GAM) and principal component analysis (PCA), we found that the aquatic system mainly exhibited interannual variations instead of seasonal variations, with nutrient loads and river discharge (turbidity and salinity) being the most prominent features affected by anthropogenic activities and climate change. Over the years, the increasing turbidity and phytoplankton showed that bottom-up effects predominated the aquatic systems. Under the bottom-up effects of eutrophication and turbidity, the phytoplankton communities showed high adaptation that MP and S1 occupied more dominance after 2016, with higher abundance but lower diversity. Moreover, the bottom-up effects further affected the structure of zooplankton communities. The dominance of rotifers filter feeders (RF) decreased over the years while middle copepods and cladocerans filter feeders (MCF) increased, implying a trend of zooplankton toward large size over time. Overall, our result reveals the bottom-up control pattern in the aquatic systems of small urban wetlands. This research provides valuable insights into the dynamics and responses of plankton communities to environmental changes in small urban wetlands, providing valuable information for future conservation efforts.

Abstract Background Acute-on-chronic liver failure (ACLF) is a critical illness with high mortality. Herein, we developed and validated a new and simple prognostic nomogram to predict 90-day mortality in hepatitis B virus-related ACLF (HBV-ACLF) patients. Methods This single-center retrospective study collected data from 181 HBV-ACLF patients treated between June 2018 and March 2020. The correlation between clinical data and 90-day mortality in patients with HBV-ACLF was assessed using univariate and multivariate logistic regression analyses. Results Multivariate logistic regression analysis showed that age (p = 0.011), hepatic encephalopathy (p = 0.001), total bilirubin (p = 0.007), international normalized ratio (p = 0.006), and high-density lipoprotein cholesterol (p = 0.011) were independent predictors of 90-day mortality in HBV-ACLF patients. A nomogram was created to predict 90-day mortality using these risk factors. The C-index for the prognostic nomogram was calculated as 0.866, and confirmed to be 0.854 via bootstrapping verification. The area under the curve was 0.870 in the external validation cohort. The predictive value of the nomogram was similar to that of the Chinese Group on the Study of Severe Hepatitis B score, and exceeded the performance of other prognostic scores. Conclusion The prognostic nomogram constructed using the factors identified in multivariate regression analysis might serve as a beneficial tool to predict 90-day mortality in HBV-ACLF patients.

In the present paper, a modified Fourier series approach is developed for new precise flexural analysis of three different types of concrete plates in a rectangular sewage tank. The bending problems of the bottom plate, side-plate, and the fluid-guiding plate are not easily solved via using the traditional analytic approaches. Based on the Fourier series theory, the present approach provides a unified semi-inverse solving procedure for the above plates by means of choosing three different kinds of Fourier series as the trial functions. Although all the trial functions are quite similar to the classical Navier-form solution, new, precise analytic flexural solutions for plates without Navier-type edge conditions (all edges simply-supported) are achieved, which is mainly attributed to employing the Stoke’s transform technique. For each case, the plate-bending problems are finally altered to deal with linear algebra equations. Furthermore, owing to the orthogonality and completeness of the Fourier series, the obtained solutions perfectly satisfy both the edge conditions and the governing partial differential equation of plates, which paves an easily implemented and rational way for engineers and researchers to provide new, exact designs of plate structures. The main contribution of this study lies in the provision of a unified solution procedure for addressing complex plate-bending problems across diverse boundary conditions. By employing a range of Fourier series types, this approach offers a comprehensive solution framework that accommodates the complexities inherent in plate analysis. The correctness of the present analytic solutions is verified against precise finite element method (FEM) results and ones available in the literature. Finally, the influences of foundation, edge conditions, and aspect ratio on flexural behaviors of plates are discussed in detail.

Abstract Background Hepatocellular carcinoma (HCC) is one of the deadliest cancers and is mainly developed from chronic liver diseases such as hepatitis-B infection-associated liver cirrhosis (LC). The progression from LC to HCC makes the detection of diagnostic biomarkers to be challenging. Hence, there have been constant efforts to improve on identifying the critical and predictive changes accompanying the disease progression. Methods In this study, we looked to using the mass spectrometry mediated spatial metabolomics technique to simultaneous examine hundreds of metabolites in an untargeted fashion. Additionally, metabolic profiles were compared between six subregions within the HCC tissue to collect spatial information. Results Through those metabolites, altered metabolic pathways in LC and HCC were identified. Specifically, the amino acid metabolisms and the glycerophospholipid metabolisms experienced the most changes. Many of the altered metabolites and metabolic pathways were able to be connected through the urea cycle. Conclusions The identification of the key metabolites and pathways can expand our knowledge on HCC metabolic reprogramming and help us exam potential biomarkers for earlier detection of the malignant disease progression.

Abstract. End-stage liver disease (ESLD) is a life-threatening clinical syndrome that markedly increases mortality in patients with infections. In patients with ESLD, infections can induce or aggravate the occurrence of liver decompensation. Consequently, infections are among the most common complications of disease progression. There is a lack of working procedure for early diagnosis and appropriate management for patients with ESLD complicated by infections as well as local and international guidelines or consensus. This consensus assembled up-to-date knowledge and experience across Chinese colleagues, providing data on principles as well as working procedures for the diagnosis and treatment of patients with ESLD complicated by infections.

Light traps are a useful method for monitoring and controlling the important migratory pest, the fall armyworm, Spodoptera frugiperda. Studies have shown that S. frugiperda is sensitive to blue, green, or ultraviolet (UV) light, but the conclusions are inconsistent. Furthermore, conventional black light traps are less effective for trapping S. frugiperda. To improve the trapping efficiency of this pest, it is crucial to determine the specific wavelength to which S. frugiperda is sensitive and measure its flight capability under that wavelength. This study investigated the effects of light wavelength on the phototaxis and flight performance of S. frugiperda. The results showed that blue light was the most sensitive wavelength among the three different LED lights and was unaffected by gender. The flight capability of S. frugiperda varied significantly in different light conditions, especially for flight speed. The fastest flight speed was observed in blue light, whereas the slowest was observed in UV light compared to dark conditions. During a 12 h flight period, speed declined more rapidly in blue light and more slowly in UV, whereas speed remained stable in dark conditions. Meanwhile, the proportion of fast-flying individuals was highest under blue light, which was significantly higher than under UV light. Therefore, the use of light traps equipped with blue LED lights can improve the trapping efficiency of S. frugiperda. These results also provide insights for further research on the effects of light pollution on migratory insects.

Objective To investigate the effect of blood donation related self-efficacy on blood donation intention, in order to provide valuable reference for formulating the recruitment and service strategy for blood donors with different demographic characteristics. Methods A questionnaire was designed based on psychological self-efficacy theory, and respondents in Nanchong city were taken as the research objects. The data of demographic characteristics, blood donation related self-efficacy measurement and blood donation intention measurement of the respondents who were randomly selected by convenient sampling method were collected and analyzed by rank sum test. Results The number of previous blood donation was significantly correlated with blood donation related self-efficacy and blood donation intention, and there was a strong positive correlation between blood donation related self-efficacy and blood donation intention (r=0.618). There are significant differences in blood donation related self-efficacy or blood donation intention of respondents with different blood donation experiences (P0.05). Conclusion Blood donation intention can be increased by enhancing the blood donation related self-efficacy of respondents. We can focus on the recruitment of respondents with high self-efficacy in the areas covered by the survey during the practice of blood donor recruitment and service to achieve higher recruitment efficiency. In the meantime, special attention should also be paid to the people with relatively low self-efficacy and high-quality services should be provided t to expand blood donor team. Furthermore, blood donor recruitment and services can be appropriately expanded to the countryside as needed.

Obesity-induced metabolic cardiomyopathy (MC), characterized by lipotoxicity and excessive oxidative stress, emerges as the leading cause of heart failure in the obese patients. Yet, its therapy remains very limited. Here, we demonstrated that isoginkgetin (IGK), a bioactive biflavonoid isolated from medicinal herb Ginkgo Biloba, protected against obesity-induced cardiac diastolic dysfunction and adverse remodeling. Transcriptomics profiling revealed that IGK activated Nrf2 signaling in the heart tissues of the obese mice. Consistent with this observation, IGK treatment increased the nuclear translocation of Nrf2, which in turn trigger the activation of its downstream target genes (e. g. HO-1 and NQO1). In addition, IGK significantly rejuvenated mitochondrial defects in obese heart tissues as evidenced by enhancing mitochondrial respiratory capacity and resisting the collapse of mitochondrial potential and oxidative stress both in vitro and in vivo. Mechanistically, IGK stabilized Nrf2 protein via inhibiting the proteasomal degradation, independent of transcription regulation. Moreover, molecular docking and dynamics simulation assessment demonstrated a good binding mode between IGK and Nrf2/Keap1. Of note, the protective effects conferred by IGK against obesity-induced mitochondrial defects and cardiac dysfunction was compromised by Nrf2 gene silencing both in vitro and in vivo, consolidating a pivotal role of Nrf2 in IGK-elicited myocardial protection against MC. Thus, the present study identifies IGK as a promising drug candidate to alleviate obesity-induced oxidative stress and cardiomyocyte damage through Nrf2 activation, highlighting the therapeutic potential of IGK in ameliorating obesity-induced cardiomyopathy.

Jade perch (Scortum barcoo) is a freshwater fish with substantial economic value, which has been widely cultivated all over the world. However, with the intensification and expansion of farming, several bacterial and viral diseases have occurred in jade perch. To understand the immune response of jade perch against Streptococcus agalactiae (Group B Streptococcus, GBS), we performed a histopathological examination and transcriptome sequencing of jade perch spleen after artificial bacterial infection. GBS infection can cause structural changes and even necrosis of the jade perch spleen, which may affect the survival of infected individuals. A total of 144,458 unigenes were obtained through de novo assembly of spleen transcriptome. Among them, 1821 unigenes were identified as DEGs, including 1415 up-regulated and 406 down-regulated unigenes in the infection group. Moreover, the analysis of GO and KEGG revealed that many GO terms and pathways were involved in the host immune response, such as Toll-like receptor signaling pathway, Cytokine-cytokine receptor interaction, and TNF signaling pathway. In addition, according to transcriptome data and qRT-PCR analysis, the expression levels of many cytokines that participate in the inflammatory response changed a lot after GBS infection. Overall, this transcriptomic analysis provided valuable information for studying the immune response of jade perch against bacterial infection.

Abstract Artemisinin and its derivatives belong to a family of drugs approved for the treatment of malaria with known clinical safety and efficacy. In addition to its anti-malarial effect, artemisinin displays anti-viral, anti-inflammatory, and anti-cancer effects in vivo and in vitro. Recently, much attention has been paid to the therapeutic role of artemisinin in liver diseases. Several studies suggest that artemisinin and its derivatives can protect the liver through different mechanisms, such as those pertaining to inflammation, proliferation, invasion, metastasis, and induction of apoptosis and autophagy. In this review, we provide a comprehensive discussion of the underlying molecular mechanisms and signaling pathways of artemisinin and its derivatives in treating liver diseases. Further pharmacological research will aid in determining whether artemisinin and its derivatives may serve as promising medicines for the treatment of liver diseases in the future.

Due to the high meat yield and rich nutritional content, jade perch (Scortum barcoo) has become an important commercial aquaculture species in China. Jade perch has a slow growth rate, taking 3–4 years to reach sexual maturity, and has almost no difference in body size between males and females. However, the study of its gonad development and reproduction regulation is still blank, which limited the yield increase. Herein, the gonad transcriptomes of juvenile males and females of S. barcoo were identified for the first time. A total of 107,060 unigenes were successfully annotated. By comparing male and female gonad transcriptomes, a total of 23,849 differentially expressed genes (DEGs) were identified, of which 9517 were downregulated, and 14,332 were upregulated in the testis. In addition, a large number of DEGs involved in sex differentiation, gonadal development and differentiation and gametogenesis were identified, and the differential expression patterns of some genes were further verified using real-time fluorescence quantitative PCR. The results of this study will provide a valuable resource for further studies on sex determination and gonadal development of S. barcoo.

The nearshore and estuary are the main gathering areas of nanoparticles (NPs), and salinity change is a crucial characteristic in these marine areas. Moina mongolica Daday is an important open-ended bait in the nearshore aquaculture environment. Investigating the toxicity mechanism of NPs to M. mongolica under different salinity conditions is crucial to exploring the biological impact of NPs in the nearshore environment. Two typical metal oxide and metal NPs of TiO2 and Ag were used in this study to test the acute, chronic, and reproductive toxicities of M. mongolica (Cladocera) in marine environments of different salinity gradients. The toxic effects and mechanisms of the two NPs on M. mongolica were discussed by ecotoxicology and transcriptional analysis, respectively. A total of 27,274 genes were assembled, and 11,056 genes were successfully compared. Results suggested that TiO2 and Ag NPs showed particle toxicity with oxidation generation and immune emergencies on M. mongolica. Compared with TiO2, Ag NPs showed strong toxicity with reproductive toxicity due to the release of Ag+, resulting in a reduction in reproduction, which is a decrease in the number of offspring and the rm. Critical DEGs involved in carapace showed carapace damage of M. mongolica, due to adhesion and accumulation (approximately 40%–60% of all accumulation) on carapace, which was one of the toxic mechanisms of the two NPs. The salinity factor caused the aggregation of both NPs, and Ag+ release of Ag NPs. The toxicity of TiO2 NPs to M. mongolica increases with salinity, but that of Ag NPs decreases.

Abstract We aim to determine the impact of an artificial liver support system (ALSS) treatment before liver transplantation (LT), and identify the prognostic factors and evaluate the predictive values of the current commonly used ACLF prognostic models for short-term prognosis after LT. Data from 166 patients who underwent LT with acute-on-chronic liver failure (ACLF) were retrospectively collected from January 2011 to December 2018 from the First Affiliated Hospital of Zhejiang University School of Medicine. Patients were divided into two groups depending on whether they received ALSS treatment pre-LT. In the observation group, liver function tests and prognostic scores were significantly lower after ALSS treatment, and the waiting time for a donor liver was significantly longer than that of the control group. Both intraoperative blood loss and period of postoperative ICU care were significantly lower; however, there were no significant differences between groups in terms of total postoperative hospital stays. Postoperative 4-week and 12-week survival rates in the observation group were significantly higher than those of the control group. Similar trends were also observed at 48 and 96 weeks, however, without significant difference. Multivariate Cox regression analysis of the risk factors related to prognosis showed that preoperative ALSS treatment, neutrophil–lymphocyte ratio, and intraoperative blood loss were independent predicting factors for 4-week survival rate after transplantation. ALSS treatment combined with LT in patients with HBV-related ACLF improved short-term survival. ALSS treatment pre-LT is an independent protective factor affecting the 4-week survival rate after LT.

Background: Intramural pregnancy (IMP) is a special type of ectopic pregnancy. The cause of the disorder nor a uniform effective treatment plan, either pharmacological or surgical treatment, has been reported. Pharmacological treatments have been associated with poor clinical outcomes and a higher risk of bleeding during treatment. Laparoscopic surgery for intramural pregnancy has been reported and timely diagnosis and early treatment by laparoscopy can reduce the adverse impact on female fertility. However, the safety and efficacy of laparoscopic treatment of intramural pregnancy has not been adequately evaluated. Methods: To evaluate the effectiveness of laparoscopic therapy of intramural pregnancy, we retrospectively selected clinical data from 12 patients with IMP treated by laparoscopy in our gynecology department (From January 2010 to December 2021). We collected clinical data from medical records, including: maternal age, gestational sac location, duration of amenorrhea, clinical symptoms, previous surgical history, pregnancy history, serum β-HCG (human chorionic gonadotropin) level, intraoperative bleeding and time of postoperative hospital stay. Results: All patients with intramural pregnancy who underwent laparoscopic surgery had their uterus preserved. Serum β-hCG decreased significantly after the operation and the average intraoperative blood loss was (50.9 ± 5.5) mL. The average length of stay was (5.4 ± 0.6) days resulting in an average hospital cost of 10,487 ± 548 RMB. Conclusions: Laparoscopic surgery is an effective and beneficial method for treating early intramural pregnancy preserving women’s uterus and protecting her future fertility.

Aberrant expression of microRNAs (miRNAs) has been reported to play a role in tumorigenesis. Dysfunction of miR-1296 was found in a variety of cancers, however, the function of miR-1296 in the progression of glioma remains largely understood. Here, our results showed that miR-1296 was significantly down-regulated in glioma tissues and cell lines. Decreased expression of miR-1296 was associated with the tumor size, WHO grade and karnofsky performance scale (KPS) of glioma patients. Low expression of miR-1296 was significantly correlated with the shorter 5-year overall survival of glioma patients. Overexpression of miR-1296 inhibited the proliferation, colony formation, migration and induced apoptosis of glioma cells. MiR-1296 was found to bind the 3’-untranslated region (UTR) of ABL proto-oncogene 2 (ABL2) and subsequently repressed both the mRNA and protein expression of ABL2. ABL2 was overexpressed in glioma tissues and inversely correlated with that of miR-1296. Ectopic expressed ABL2 could reverse the inhibitory effects of miR-1296 on glioma cell proliferation. Our results illustrated the novel tumor-suppressive function of miR-1296 in glioma via repressing ABL2, suggesting a potential application of miR-1296 in the treatment of glioma.

Uncovering microbial response to salinization or desalinization is of great importance to understanding of the influence of global climate change on lacustrine microbial ecology. In this study, to simulate salinization and desalinization, sediments from Erhai Lake (salinity 0.3–0.8 g/L) and Chaka Lake (salinity 299.3–350.7 g/L) on the Qinghai–Tibetan Plateau were transplanted into different lakes with a range of salinity of 0.3–299.3 g/L, followed by in situ incubation for 50 days and subsequent geochemical and microbial analyses. Desalinization was faster than salinization in the transplanted sediments. The salinity of the transplanted sediment increased and decreased in the salinization and desalinization simulation experiments, respectively. The TOC contents of the transplanted sediments were lower than that of their undisturbed counterparts in the salinization experiments, whereas they had a strong negative linear relationship with salinity in the desalinization experiments. Microbial diversity decreased in response to salinization and desalinization, and microbial community dissimilarity significantly (P < 0.01) increased with salinity differences between the transplanted sediments and their undisturbed counterparts. Microbial groups belonging to Gammaproteobacteria and Actinobacteria became abundant in salinization whereas Bacteroidetes and Chloroflexi became dominant in desalinization. Among the predicted microbial functions, hydrogenotrophic methanogenesis, methanogenesis through CO2 reduction with H2, nitrate/nitrogen respiration, and nitrification increased in salinization; in desalinization, enhancement was observed for respiration of sulfur compounds, sulfate respiration, sulfur respiration, thiosulfate respiration, hydrocarbon degradation, chemoheterotrophy, and fermentation, whereas depressing was found for aerobic ammonia oxidation, nitrate/nitrogen respiration, nitrification, nitrite respiration, manganese oxidation, aerobic chemoheterotrophy, and phototrophy. Such microbial variations could be explained by changes of transplantation, salinity, and covarying variables. In summary, salinization and desalinization had profound influence on the geochemistry, microbial community, and function in lakes.

Background/Aims: Pseudomonas aeruginosa (PA) is one of the major opportunistic pathogens which can cause chronic lung infection of cystic fibrosis (CF). The formation of PA biofilm promotes CF development and restricts the antimicrobial efficacies of current antibiotics. Methods: The antimicrobial effects of azithromycin (AZM) and berberine (BER) alone and in combination were evaluated using microdilution method, checkerboard assay, time-kill test, qRT-PCR analysis and absorption method. The treatments of AZM and/or BER were further evaluated in an animal lung infection model via observing survival rate, bacterial burden and histopathology of lung, the levels of pro-/anti-inflammatory cytokines. Results: AZM-BER were demonstrated to be synergistic against ten clinical PA isolates as well as the standard reference PA ATCC27853, in which PA03 was the most susceptible isolate to AZM-BER with FICI of 0.13 and chosen for subsequent experiments. The synergism of AZM-BER was further confirmed against PA03 in time-kill test and scanning electron microscope (SEM) at their concentrations showing synergism. In PA03, we found that AZM-BER could significantly attenuate productions of a series of virulence factors including alginate, LasA protease, LasB protease, pyoverdin, pyocyanin, chitinase as well as extracellular DNA, and remarkably inhibit the levels of quorum sensing (QS) molecules and the expressions of lasI, lasR, rhlI, rhlR at 1/2×MIC, 1×MIC and 2×MIC. In the infection model, the mice survival were increased markedly, the inflammations of infected lungs were improved greatly along with reduced IL-6, IL-8 and ascended IL-10 at 0.8 mg/kg of AZM combined with 3.2 mg/kg of BER. Conclusion: BER might be a promising synergist to enhance the antimicrobial activity of AZM in vitro and in vivo.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

To escape or alleviate low temperatures in winter, insects have evolved many behavioral and physiological strategies. The purple stem borer, Sesamia inferens (Walker) is currently reported to be expanding their northern distributions and causing damage to summer maize in Xinxiang, China. However, their method of coping with the lower temperature in the new northern breeding area in winter is largely unknown. This paper investigates the overwinter site of S. inferens, and identifies the cold hardiness of larvae collected from a new breeding area in winter and explores a potential distribution based on low temperature threshold and on species distribution model MaxEnt. The results show that the overwintering location of the S. inferens population is more likely to be underground with increasing latitude and the population gradually moved down the corn stalk and drilled completely underground in later winter (February) in the north. The cold hardiness test shows the species is a moderate freeze-tolerant one, and Supercooling Points (SCP), Freezing Points (FP) and the incidence of mortality during the middle of winter (January, SCP: -7.653, FP: -6.596) were significantly lower than early winter (October) or late winter (March). Distribution in the new expansion area was predicted and the survival probability area was below N 35° for the Air Lower Lethal Temperature (ALLT50) and below N 40° for the Underground Lower Lethal Temperature (ULLT50). The suitable habitat areas for S. inferens with MaxEnt were also below N 40°. This study suggests the overwinter strategies of S. inferens have led to the colonization of up to a five degree more northerly overwintering latitude.

A chemiluminescent immunoassay for human serum osteocalcin, or bone Gla protein, was established using a double-antibody sandwich model. Examination of the hook effect revealed that it was significantly reduced, and no hook effect was observed at an osteocalcin concentration of 4000 ng/mL. The established method showed good analytical performance and thermal stability. The limit of detection was 0.03 ng/mL. The intra-assay coefficient of variation (CV) was 3.22%–5.64%, the interassay CV was 4.42%–7.25%, and the recovery rate was 93.22%–107.99%. Cross-reactivity (CR) was not observed with bovine, rat, mouse, rabbit, or porcine samples. The developed method showed a good correlation with the N-MID product from Roche. In total, 1069 clinical patient samples were measured using the reagent kit developed in this study.

Naringin palmitate is an acylated product of naringin with palmitic acid, which is an effective substance for enhancing naringin lipophilicity. Lysozyme has strong ability to carry drugs and functional compounds in mammals. Herein, the ability of lysozyme to carry naringin palmitate was investigated by fluorescence and UV spectroscopy, and the differences in affinities of naringin and naringin palmitate for lysozyme were compared. Naringin palmitate was found to quench the fluorescence of lysozyme via static quenching. The binding constant and number of binding sites of naringin palmitate–lysozyme were more sensitive to high temperature than naringin–lysozyme. van der Waals forces and hydrogen bond formation played a major role in stabilizing naringin palmitate–lysozyme. No significant change of the structure and microenvironment of lyzozyme were obtained by addition of naringin palmitate. Thus, transport of naringin palmitate by lysozyme was verified. These findings are of importance and are attractive for the practical applications of naringin palmitate.

Introduction. The application of nucleos(t)ide analogues in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) has not yet been widely accepted. Therefore, we conducted a meta-analysis of prospective and retrospective studies to examine the efficacy and safety of nucleos(t)ide analogues in treating HBV-related ACLF.Material and methods. Two independent reviewers identified eligible studies through electronic, and manual searches, and contact with experts. Three-month mortality was defined as the primary efficacy measure. ACLF reactivation and HBV DNA inhibition were secondary efficacy measures. Quantitative meta-analyses were performed to compare differences between nucleos(t)ide analogue and control groups.Results. Five eligible studies were identified. Antiviral treatment with nucleos(t)ide analogues led to significant reduction of HBV DNA [HBV DNA reduction > 2 log: 70.4 vs. 29%, RR = 2.29, 95%CI (1.49, 3.53), P < 0.01]. ACLF patients receiving nucleos(t)ide analogue had significantly lower 3-month mortality [44.8 vs. 73.3%, RR = 0.68, 95%CI (0.54, 0.84), P < 0.01] as well as incidence of reactivation [1.80 vs. 18.4%, RR = 0.11, 95%CI (0.03, 0.43), P < 0.01] compared to those who did not. There was no significant difference in the prognosis of patients treated with entecavir or lamivudine [36.4 vs. 40.5%, RR = 0.77, 95%CI (0.45, 1.32), P = 0.35]. No drug-related adverse events were reported during follow-up.Conclusion. Our findings suggest that nucleos(t)ide analogue treatment reduces short-term mortality as well as reactivation of HBV-related ACLF patients. Nucleos(t)ide analogues are well-tolerated during therapy, and suggestive evidence indicates that entecavir and lamivudine confer comparable short-term benefits in these patients. However, further studies are needed to clarify these observations.

OBJECTIVE: Previous studies regarding the association between parental smoking and the risk of childhood brain tumors (CBT) have reported inconsistent results. We performed a meta-analysis to summarize evidence on this association and to quantify the potential dose-response relationship. METHODS: A systematic literature search was conducted in the Medline and Embase databases. The summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated. Dose-response meta-analysis was also performed for studies that reported categorical risk estimates for a series of smoking exposure levels. RESULTS: A total of 17 studies fulfilled the inclusion criteria. In the meta-analyses, the summary RRs (95% CIs) of CBT for maternal smoking during pregnancy, paternal smoking during pregnancy, maternal smoking before pregnancy, and paternal smoking before pregnancy were 0.96 (0.86-1.07), 1.09 (0.97-1.22), 0.93 (0.85-1.00), and 1.09 (1.00-1.20), respectively. Dose-response meta-analysis also showed no significant association between parental smoking and the risk of CBT. CONCLUSIONS: Findings from our meta-analysis indicate that parental smoking may not be associated with a risk of CBT.

BackgroundBovine serum albumin (BSA) contains high affinity binding sites for several endogenous and exogenous compounds and has been used to replace human serum albumin (HSA), as these two compounds share a similar structure. Naringin palmitate is a modified product of naringin that is produced by an acylation reaction with palmitic acid, which is considered to be an effective substance for enhancing naringin lipophilicity. In this study, the interaction of naringin palmitate with BSA was characterised by spectroscopic and molecular docking techniques.Methodology/principal findingsThe goal of this study was to investigate the interactions between naringin palmitate and BSA under physiological conditions, and differences in naringin and naringin palmitate affinities for BSA were further compared and analysed. The formation of naringin palmitate-BSA was revealed by fluorescence quenching, and the Stern-Volmer quenching constant (KSV ) was found to decrease with increasing temperature, suggesting that a static quenching mechanism was involved. The changes in enthalpy (ΔH) and entropy (ΔS) for the interaction were detected at -4.11 ± 0.18 kJ·mol(-1) and -76.59 ± 0.32 J·mol(-1)·K(-1), respectively, which indicated that the naringin palmitate-BSA interaction occurred mainly through van der Waals forces and hydrogen bond formation. The negative free energy change (ΔG) values of naringin palmitate at different temperatures suggested a spontaneous interaction. Circular dichroism studies revealed that the α-helical content of BSA decreased after interacting with naringin palmitate. Displacement studies suggested that naringin palmitate was partially bound to site I (subdomain IIA) of the BSA, which was also substantiated by the molecular docking studies.Conclusions/significanceIn conclusion, naringin palmitate was transported by BSA and was easily removed afterwards. As a consequence, an extension of naringin applications for use in food, cosmetic and medicinal preparations may be clinically and practically significant, especially in the design of new naringin palmitate-inspired drugs.

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is one of the most deadly, prevalent, and costly diseases in Asia. However, no prognostic model has been developed that is based specifically on data gathered from Asian patients with ACLF. The aim of the present study was to quantify the survival time of ACLF among Asians and to develop a prognostic model to estimate the probability of death related to ACLF. METHODS: We conducted a retrospective observational cohort study to analyze clinical data from 857 patients with ACLF/pre-ACLF who did not undergo liver transplantation. Kaplan-Meier and Cox proportional hazards regression model were used to estimate survival rates and survival affected factors. The area under the receiver operating characteristic curve (auROC) was used to evaluate the performance of the models for predicting early mortality. RESULTS: The mortality rates among patients with pre-ACLF at 12 weeks and 24 weeks after diagnosis were 30.5% and 33.2%, respectively. The mortality rates among patients with early-stage ACLF at 12 weeks and 24 weeks after diagnosis were 33.9% and 37.1%, respectively. The difference in survival between pre-ACLF patients and patients in the early stage of ACLF was not statistically significant. The prognostic model identified 5 independent factors significantly associated with survival among patients with ACLF and pre-ACLF: the model for end-stage liver disease (MELD) score; age, hepatic encephalopathy; triglyceride level and platelet count. CONCLUSION: The findings of the present study suggest that the Chinese diagnostic criteria of ACLF might be broadened, thus enabling implementation of a novel model to predict ACLF-related death after comprehensive medical treatment.

BACKGROUND:The search for a strategy to provide temporary liver support and salvage the patients with acute-on-chronic liver failure (ACLF) remains an important issue. This study was designed to evaluate the experience in artificial liver support system (ALSS) combined with liver transplantation (LT) in the treatment of ACLF. METHODOLOGY/PRINCIPAL FINDINGS:One hundred and seventy one patients with HBV related ACLF undergoing LT between January 2001 and December 2009 were included. Of the 171 patients, 115 received 247 sessions of plasma exchange-centered ALSS treatment prior to LT (ALSS-LT group) and the other 56 received emergency LT (LT group). The MELD score were 31±6 and 30±7 in ALSS-LT group and LT group. ALSS treatment resulted in improvement of liver function and better tolerance to LT. The average level of serum total bilirubin before LT was lower than that before the first time of ALSS treatment. The median waiting time for a donor liver was 12 days (2-226 days) from the first run of ALSS treatment to LT. Compared to LT group, the beneficial influences of ALSS on intraoperative blood loss and endotracheal intubation time were also observed in ALSS-LT group. The 1-year and 5-year survival rates in the ALSS-LT group and LT group were 79.2% and 83%, 69.7% and 78.6%. CONCLUSIONS/SIGNIFICANCE:Plasma exchange-centered ALSS is beneficial in salvaging patients with ACLF when a donor liver is not available. The consequential LT is the fundamental treatment modality to rescue these patients and lead to a similar survival rate as those patients receiving emergency transplantation.

Protein phosphorylation is a complex regulatory event that is involved in the signaling networks that affect virtually every cellular process. The protein phosphorylation may be a novel source for discovering biomarkers and drug targets. However, a systematic analysis of the phosphoproteome in patients with SLE has not been performed. To clarify the pathogenesis of systemic lupus erythematosus (SLE), we compared phosphoprotein expression in PBMCs from SLE patients and normal subjects using proteomics analyses. Phosphopeptides were enriched using TiO₂ from PBMCs isolated from 15 SLE patients and 15 healthy subjects and then analyzed by automated LC-MS/MS analysis. Phosphorylation sites were identified and quantitated by MASCOT and MaxQuant. A total of 1035 phosphorylation sites corresponding to 618 NCBI-annotated genes were identified in SLE patients compared with normal subjects. Differentially expressed proteins, peptides and phosphorylation sites were then subjected to bioinformatics analyses. Gene ontology(GO) and pathway analyses showed that nucleic acid metabolism, cellular component organization, transport and multicellular organismal development pathways made up the largest proportions of the differentially expressed genes. Pathway analyses showed that the mitogen-activated protein kinase (MAPK) signaling pathway and actin cytoskeleton regulators made up the largest proportions of the metabolic pathways. Network analysis showed that rous sarcoma oncogene (SRC), v-rel reticuloendotheliosis viral oncogene homolog A (RELA), histone deacetylase (HDA1C) and protein kinase C, delta (PRKCD) play important roles in the stability of the network. These data suggest that aberrant protein phosphorylation may contribute to SLE pathogenesis.