[Real-time Detection Method for Motion Artifact of Photoplethysmography Signals Based on Decision Trees].

PPG (photoplethysmography) holds significant application value in wearable and intelligent health devices. However, during the acquisition process, PPG signals can generate motion artifacts due to inevitable coupling motion, which diminishes signal quality. In response to the challenge of real-time detection of motion artifacts in PPG signals, this study analyzed the generation and significant features of PPG signal interference. Seven features were extracted from the pulse interval data, and those exhibiting notable changes were filtered using the dual-sample Kolmogorov-Smirnov test. The real-time detection of motion artifacts in PPG signals was ultimately based on decision trees. In the experimental phase, PPG signal data from 20 college students were collected to formulate the experimental dataset. The experimental results demonstrate that the proposed method achieves an average accuracy of (94.07±1.14)%, outperforming commonly used motion artifact detection algorithms in terms of accuracy and real-time performance.

Metatranscriptomics and metabarcoding reveal spatiotemporal shifts in fungal communities and their activities in Chinese coastal waters.

Fungal communities are diverse and abundant in coastal waters, yet, their ecological roles and adaptations remain largely unknown. To address these gaps, ITS2 metabarcoding and metatranscriptomic analyses were used to capture the whole suite of fungal diversity and their metabolic potential in water column and sediments in the Yellow Sea during August and October 2019. ITS2 metabarcoding described successfully the abundance of Dikarya during August and October at the different examined habitats, but strongly underrepresented or failed to identify other fungal taxa, including zoosporic and early-diverging lineages, that were abundant in the mycobiome as uncovered by metatranscriptomes. Metatranscriptomics also revealed enriched expression of genes annotated to zoosporic fungi (e.g., chytrids) mainly in the surface water column in October. This enriched expression was correlated with the two-fold increase in chlorophyll-a intensity attributed to phytoplanktonic species which are known to be parasitized by chytrids. The concurrent high expression of genes related to calcium signalling and GTPase activity suggested that these metabolic traits facilitate the parasitic lifestyle of chytrids. Similarly, elevated expression of phagosome genes annotated to Rozellomycota, an early-diverging fungal phylum not fully detected with ITS2 metabarcoding, suggested that this taxon utilizes a suite of feeding modes, including phagotrophy in this coastal setting. Our data highlight the necessity of using combined approaches to accurately describe the community structure of coastal mycobiome. We also provide in-depth insights into the fungal ecological roles in coastal waters, and report potential metabolic mechanisms utilized by fungi to cope with environmental stresses that occur during distinct seasonal months in coastal ecosystems.

Klotho inhibits renal ox-LDL deposition via IGF-1R/RAC1/OLR1 signaling to ameliorate podocyte injury in diabetic kidney disease.

OBJECTIVE: Diabetic kidney disease (DKD) is characterized by the abnormal deposition of oxidized low-density lipoprotein (ox-LDL), which contributes to podocyte damage. Klotho, an aging suppressor that plays a critical role in protecting podocytes in DKD, is mainly expressed in kidney tubular epithelium and secreted in the blood. However, it has not been established whether Klotho can alleviate podocyte injury by inhibiting renal ox-LDL deposition, and the potential molecular mechanisms require further investigation. METHODS: We conducted a comprehensive analysis of serum and kidney biopsy samples obtained from patients diagnosed with DKD. Additionally, to explore the underlying mechanism of Klotho in the deposition of ox-LDL in the kidneys, we employed a mouse model of DKD with the Klotho genotype induced by streptozotocin (STZ). Furthermore, we conducted meticulous in vitro experiments on podocytes to gain further insights into the specific role of Klotho in the deposition of ox-LDL within the kidney. RESULTS: Our groundbreaking study unveiled the remarkable ability of the soluble form of Klotho to effectively inhibit high glucose-induced ox-LDL deposition in podocytes affected by DKD. Subsequent investigations elucidated that Klotho achieved this inhibition by reducing the expression of the insulin/insulin-like growth factor 1 receptor (IGF-1R), consequently leading to a decrease in the expression of Ras-related C3 botulinum toxin substrate 1 (RAC1) and an enhancement of mitochondrial function. Ultimately, this series of events culminated in a significant reduction in the expression of the oxidized low-density lipoprotein receptor (OLR1), thereby resulting in a notable decrease in renal ox-LDL deposition in DKD. CONCLUSION: Our findings suggested that Klotho had the potential to mitigate podocyte injury and reduced high glucose-induced ox-LDL deposition in glomerulus by modulating the IGF-1R/RAC1/OLR1 signaling. These results provided valuable insights that could inform the development of novel strategies for diagnosing and treating DKD.

Growth hormone treatment in pre-pubertal short Chinese children with chronic kidney disease prior to transplantation.

BACKGROUND: The effect of recombinant human GH (rhGH) in Chinese children with chronic kidney disease (CKD) is unclear. METHODS: This was a 52-week, multicenter, randomized, open-label, negative-controlled phase 3 study. Prepubertal subjects were randomized 1:1 to either daily subcutaneous injections of rhGH 0.05 mg/kg/day or no treatment for 52 weeks. RESULTS: A total of 68 subjects with a mean age of 7.8 ± 3.27 years were enrolled. At week 52, the height standard deviation score (HT-SDS) in the treated group increased by 0.75 ± 0.58, which was significantly higher compared with 0.17 ± 0.47 in the untreated group (least squares mean 0.58, 95% confidence interval, 0.32-0.84; P < 0.001). At week 52, significant improvements were observed in other growth parameters (height velocity [P < 0.001]), insulin-like growth factor 1 (IGF-1) SDS [P < 0.001], IFG-1/insulin-like growth factor binding protein-3 molar ratio [P < 0.001], and height [P < 0.001]) compared with the untreated control. Seven patients reported treatment-related adverse events (TRAEs) and most TRAEs were mild in severity. Most subjects recovered without further intervention. CONCLUSIONS: Daily rhGH for 52 weeks in children with CKD-induced growth retardation significantly improved HT-SDS and other growth parameters without compromising safety. IMPACT: The efficacy and safety of growth hormone (GH) therapy in Chinese children with chronic kidney disease (CKD) are unclear. This study found that giving short stature Chinese children with CKD daily recombinant human growth hormone (rhGH) for 52 weeks improved growth parameters without compromising safety. This study's information can give physicians the confidence to treat these patients in their clinical practice.

Interferon gamma regulates a complex pro-survival signal network in chronic lymphocytic leukemia.

BACKGROUND: It is known that the microenvironmental cytokine interferon gamma (IFN-γ) provides a survival advantage for chronic lymphocytic leukemia (CLL) cells. However, the mechanisms involved in this effect have not been properly investigated. METHODS: Herein, we conducted a comprehensive screening of the effects of IFN-γ on signaling pathways and gene expression profiles in CLL cells by using western blotting, real-time quantitative reverse transcription (RT-qPCR) and high-throughput RNA sequencing (RNA-seq). RESULTS: We found that IFN-γ not only activated the pro-survival signal transducer and activator of transcription 3 (STAT3), but also activated the protein kinase B and extracellular signal-regulated kinase signaling pathways. RNA-seq analysis showed that IFN-γ stimulation changed the expression profiles of more than 500 genes, with 391 being up-regulated and 123 down-regulated. These genes are involved in numerous biological processes, including anti-apoptosis, cell migration, and proliferation. IFN-γ significantly up-regulated the expression of CD38, BCL6, CXCL9, BCL2A1, SCOS3, IL-10, HGF, EGFR, THBS-1, FN1, and MUC1, which encode proteins potentially associated with disease progression, worse prognosis or poor response to treatment. Blocking janus kinases1/2 (JAK1/2) or STAT3 signal by specific inhibitors affected the expression of most genes, suggesting a pivotal role of the JAK1/2-STAT3 pathway in IFN-γ pro-survival effects in CLL. CONCLUSIONS: Our data demonstrate that IFN-γ regulates a complex pro-survival signal network in CLL through JAK1/2-STAT3, which provides a rational explanation for IFN-γ promoting CLL cells survival and drug resistance.

Safety and efficacy of jaktinib (a novel JAK inhibitor) in patients with myelofibrosis who are intolerant to ruxolitinib: A single-arm, open-label, phase 2, multicenter study.

Although ruxolitinib improves splenomegaly and constitutional symptoms in patients with myelofibrosis (MF), a substantial proportion of patients discontinue ruxolitinib because of intolerance. This phase 2 trial investigated the safety and efficacy of jaktinib, a novel JAK inhibitor in patients with ruxolitinib-intolerant MF. The primary endpoint was the proportion of patients with ≥35% reduction in spleen volume (SVR35) at week 24. The secondary endpoints included change of MF-related symptoms, anemic response, and safety profiles. Between December 18, 2019, and November 24, 2021, 51 patients were enrolled, 45 treated with jaktinib 100 mg bid (100 mg bid group) and six received non-100 mg bid doses (non-100 mg bid group). The SVR35 at week 24 in the 100 mg bid group was 43.2% (19/44, 95% CI 29.7%-57.8%). There were 41.9% (13/31) of transfusion-independent patients with hemoglobin (HGB) ≤100 g/L who had HGB elevation ≥20 g/L within 24 weeks. The proportion of patients with a ≥50% decrease in the total symptom score (TSS 50) at week 24 was 61.8% (21/34). The most commonly reported grade ≥3 treatment-emergent adverse events (TEAEs) in the 100 mg bid group were anemia 31.1%, thrombocytopenia 22.2%, and infectious pneumonia 17.8%. A total of 16 (35.6%) in the 100 mg bid group had serious adverse events, and 4 (8.9%) were considered possibly drug related. These results indicate jaktinib can provide a treatment option for patients with MF who are intolerant to ruxolitinib.

Safety and efficacy of jaktinib (a novel JAK inhibitor) in patients with myelofibrosis who are relapsed or refractory to ruxolitinib: A single-arm, open-label, phase 2, multicenter study.

Ruxolitinib has demonstrated efficacy in patients with myelofibrosis (MF). However, substantial number of patients may not respond after 3-6 months of treatment or develop resistance over time. In this phase 2 trial, patients with a current diagnosis of intermediate or high-risk MF who either had an inadequate splenic response or spleen regrowth after ruxolitinib treatment were enrolled. All patients received jaktinib 100 mg Bid. The primary endpoint was the proportion of patients with ≥35% reduction in spleen volume (SVR 35) at week 24. The secondary endpoints included change of MF-related symptoms, anemic response, and safety profile. From July 6, 2021, to January 24, 2022, 34 ruxolitinib-refractory or relapsed patients were enrolled, 52.9% (18 of 34) were DIPSS intermediate 2 or high risk. SVR 35 at week 24 was 32.4% (11 of 34, 95% CI 19.1%-49.2%) in all patients and 33.3% (6 of 18, 95% CI 16.3%-56.3%) in the intermediate 2 or high-risk group. A total of 50% (8 of 16) transfusion-independent patients with hemoglobin (HGB) <100 g/L at baseline had HGB elevation ≥20 g/L within 24 weeks. Furthermore, 46.4% (13 of 28) of patients had a ≥ 50% decrease in the total symptom score (TSS 50) at week 24. The most common grade ≥3 treatment-emergent adverse events (TEAEs) were thrombocytopenia (32.4%), anemia (32.4%), and leukocytosis (20.6%). In total, 13 (38.2%) of 34 patients had serious adverse events (SAE), of which drug-related SAEs were found in 5 patients (14.7%). These results indicate that jaktinib can be a promising treatment option for patients with MF who have either become refractory to or relapsed after ruxolitinib treatment.

Algae Pyrolysis in Molten NaOH-Na2CO3 for Hydrogen Production.

Biomass pyrolysis within the alkaline molten salt is attractive due to its ability to achieve high hydrogen yield under relatively mild conditions. However, poor contact between biomass, especially the biomass pellet, and hydroxide during the slow heating process, as well as low reaction temperatures, become key factors limiting the hydrogen production. To address these challenges, fast pyrolysis of the algae pellet in molten NaOH-Na2CO3 was conducted at 550, 650, and 750 °C. Algae were chosen as feedstock for their high photosynthetic efficiency and growth rate, and the concept of coupling molten salt with concentrated solar energy was proposed to address the issue of high energy consumption at high temperatures. At 750 °C, the pollutant gases containing Cl and S were completely removed, and the HCN removal rate reached 44.92%. During the continuous pyrolysis process, after a slight increase, the hydrogen yield remained stable at 71.48 mmol/g-algae and constituted 86.10% of the gas products, and a minimum theoretical hydrogen production efficiency of algae can reach 84.86%. Most importantly, the evolution of physicochemical properties of molten NaOH-Na2CO3 was revealed for the first time. Combined with the conversion characteristics of feedstock and gas products, this study provides practical guidance for large-scale application of molten salt including feedstock, operation parameters, and post-treatment process.

Value of the modified semiquantitative classification in predicting outcomes in children with Henoch-Schönlein purpura nephritis.

BACKGROUND: The modified semiquantitative classification (SQC) is a new pathological classification for Henoch-Schönlein purpura nephritis (HSPN), and its prognostic value with regard to the outcomes of HSPN is unclear. METHODS: We performed a retrospective review of 249 patients with biopsy-proven HSPN admitted to the Children's Hospital of Chongqing Medical University. In addition to the International Study of Kidney Disease in Children (ISKDC) classification, renal biopsy specimens were also reevaluated according to the SQC. RESULTS: During the follow-up period of 2.9 (1.0-6.9) years, 14 (5.6%) patients reached the poor outcome at the end of follow-up. The SQC activity and chronicity indexes were positively correlated with the clinical manifestations, conventional pathology grades, and 24-h urinary protein (24hUP). The difference in the areas under the curve between the total biopsy SQC scores and ISKDC classification was 0.12 (p = .001, 95% CI: 0.0485-0.192). In the receiver operating characteristic (ROC) curve analysis of 1-year, 3-year, and 5-year poor outcomes and total biopsy SQC scores, a total biopsy score ≥10 was associated with a higher risk of an adverse outcome. CONCLUSION: Our study suggests that the SQC indexes are clearly correlated with the clinical and pathological findings of HSPN. The SQC is more sensitive than ISKDC classification for the prediction of the long-term outcomes of HSPN in children.

The nitrogen and carbon footprints of ammonia synthesis in China based on life cycle assessment.

The global nitrogen (N) cycle has emerged as an earth system process with more serious artificial disruption than climate change. Artificially synthesized reactive nitrogen (Nr) already accounts for nearly 50% of the total Nr in the earth system. The massive anthropogenic conversion of inert nitrogen (N2) to Nr is a major driver of imbalance and disruption of the earth's N cycle, where the artificial ammonia (NH3) synthesis process is the main trigger. Existing studies on life cycle environmental impacts of ammonia synthesis mainly focused on the greenhouse effect but lacked or underestimated the interference with the nitrogen cycle due to currently incomplete nitrogen footprint frameworks. In addition, the comprehensive evaluation of the nexus between nitrogen and carbon footprint of NH3 synthesis systems is also insufficient. Attempting to solve the above-mentioned problems, life cycle assessment models of seven ammonia synthesis systems were established considering different raw material pathways and production technologies under China's context, assisted by the Brightway2 platform. The general framework of nitrogen footprint accounting (GFNFA) that was established by the authors previously was employed to assess the ammonia synthesis on nitrogen footprint covered all ecosphere. The performance and hotspots of the system nitrogen footprint, carbon footprint (CF) and nitrogen-carbon nexus were then systematically quantified and analyzed. Results indicated that electrolysis-based ammonia powered by renewable and nuclear energy had the lowest Nr emission (0.499-1.148 kg Nr/t NH3) and carbon emission (592.822-1045.494 kg CO2-eq/t NH3). Among the seven ammonia synthesis systems investigated, biomass-based ammonia had the largest Nr emission and system nitrogen accumulation, and it converts the most N2 to Nr per ton ammonia produced, due to the extensive resources consumption and emissions during straw growth and direct Nr emission in gasification process. Thus, it caused the most significant disturbance to the earth's nitrogen cycle. The nexus between nitrogen and carbon footprints was revealed that the system's energy consumption was found to be a common driver through hotspots and contribution analysis. NH3 synthesis efficiency was the most determining factor in the system's Nr and carbon emissions. With a 15% increase in synthesis efficiency, nitrogen and carbon footprints can be reduced by more than 12.5%. This study can help researchers better understand the life cycle impacts of ammonia synthesis systems on earth's nitrogen and carbon cycle from multidisciplinary ecological origins.

Novel pathogenic variants in CUBN uncouple proteinuria from renal function.

BACKGROUND: Proteinuria is an unfavorable clinical condition highly associated with a risk of renal and cardiovascular disease in chronic kidney disease (CKD). However, whether all proteinuria forms are linked to renal impairment are still unclear. Cubilin is an endocytic receptor highly expressed in renal proximal tubules mediating uptake of albumin, transferrin and α1-microglobulin. METHODS: Exome sequencing method initially identified candidate genes. With the application of exome sequencing combined with Sanger sequencing, we further focused on CUBN through bioinformatics analysis. The pathogenic effects of the potentially causative variants were verified utilizing complementary analysis of clinical data and systematic characterization of the variants' expression and function with clinical samples and in vitro experiments in HEK293T cell lines along with in vivo experiments in mice. RESULTS: In this study, we identified four novel variants locating after the vitamin B12 (vitB12)-binding domain of Cubilin (encoded by CUBN, NM_001081.3: c.4397G > A (p.C1466Y), c.6796C > T (p.R2266X), c.6821 + 3A > G and c.5153_5154delCT (p.S1718X)) in two families. Moreover, the variants severely affected the expression and function of Cubilin in renal proximal tubules and caused albuminuria, increasing levels in urine transferrin and α1-microglobulin, but without progressive glomerular filtration barrier (GFB) impairment, vitB12 deficiencies or abnormal blood levels of HDL and albumin. Further mechanistic insights showed that the variants after the vitB12-binding domain of CUBN merely disrupted the association with Amnionless (AMN) that exhibited aberrant localization in cell cytoplasm rather than membrane. CONCLUSIONS: Here, our findings suggested that different mutation types after the vitB12-binding domain of CUBN uncouple proteinuria from glomerular filtration barrier, that may be an unexpectedly common benign condition in humans and may not require any proteinuria-lowering treatment or renal biopsy.

Targeting CD33 for acute myeloid leukemia therapy.

BACKGROUND: The aim of this study was to analyze the level of CD33 expression in patients with newly diagnosed AML and determine its correlation with clinical characteristics. METHODS: Samples were collected for analysis from AML patients at diagnosis. We evaluated the level of CD33 expression by flow cytometry analysis of bone marrow. Chi-square or t- tests were used to assess the association between the high and low CD33 expression groups. Survival curves were generated by the Kaplan-Meier and Cox regression model method. RESULTS: In this study we evaluated the level of CD33 expression in de novo patients diagnosed from November 2013 until January 2019. The mean value of 73.4% was used as the cutoff for the two groups. Statistical analysis revealed that 53 of the 86 (61.2%) AML patients were above the mean. Although there was no statistical significance between CD33 expression level and gene mutation, FLT3 mutation (P = 0.002) and NPM1 mutation (P = 0.001) were more likely to be seen in the high CD33 group. The overall survival (OS) was worse in the high CD33 group (39.0 m vs. 16.7 m, x2 = 13.06, P < 0.001). The Cox survival regression display that the CD33 is independent prognostic marker (HR =0.233,p = 0.008). Univariate analysis showed that the high expression of CD33 was an unfavorable prognostic factor. Of the 86 patients, CD33-high was closely related to the patients with normal karyotype (x2 = 4.891,P = 0.027), high white blood cell count (WBC, t = 2.804, P = 0.007), and a high ratio of primitive cells (t = 2.851, P = 0.005). CONCLUSIONS: These findings provide a strong rationale for targeting CD33 in combination with chemotherapy, which can be considered a promising therapeutic strategy for AML.

Clinical manifestations, prognosis, and treat-to-target assessment of pediatric lupus nephritis.

BACKGROUND: Pediatric lupus nephritis (pLN) is one of the most refractory secondary kidney diseases in childhood. The treat-to-target (T2T) strategy has become the standard treatment for systemic lupus erythematosus (SLE). This study reviewed clinical features, overall remission status, and factors affecting prognosis, to guide pLN management according to T2T strategy. METHODS: This single-center retrospective study studied 220 children diagnosed with LN from January 2012 to December 2018, with > 6-month follow-up data on 173 and complete data on 137 patients. Primary outcome was treatment failure (deterioration or no response) at the latest follow-up. RESULTS: The most common pLN manifestation was proteinuria (81.36%). Females presented more often with rash (P<0.001) and alopecia (P=0.026) than males. Class IV LN (33.33%) was the most common grade on kidney biopsy. Median follow-up was 27.20 months (IQR, 15.78-44.45 months). One-, 3-, and 5-year cumulative overall survival rates were 93.5%, 87.8%, and 86.5%, respectively. The 5-year cumulative kidney survival rate was 97.1%. Regarding initial therapy, efficacy of corticosteroids combined with immunosuppressive agents was significantly better than corticosteroids alone (P=0.010). Factors with P<0.05 in univariate analysis, including hypoalbuminemia, higher SCr at diagnosis, lower eGFR at diagnosis, anti-dsDNA positivity, heavy proteinuria, hypertension, nervous-system involvement, treatment non-compliance, and SLEDAI-2K score, were used for logistic regression analysis. Logistic regression analysis showed hypertension (OR=0.845, P=0.011), nervous-system involvement (OR=4.240, P=0.005), treatment non-compliance (OR=6.433, P=0.001), and lower estimated glomerular filtration rate at diagnosis (OR=1.020, P=0.021) affected prognosis. At end of follow-up, 34.31% achieved varying levels of remission, and 8.76% were in low disease activity state (LDAS). CONCLUSIONS: pLN usually presented with proteinuria, and class IV LN was the dominant pathology. Hypertension, nervous-system involvement, treatment non-compliance, and lower eGFR at diagnosis were independent risk factors for poor prognosis of kidney outcomes. Compared with renal remission rate and cumulative overall survival rate, the proportion of targets achieved was not ideal, suggesting T2T strategy should be used to guide pLN management. A higher resolution version of the Graphical abstract is available as Supplementary information.

Enhanced Semantic Information Transfer of Multi-Domain Samples: An Adversarial Edge Detection Method Using Few High-Resolution Remote Sensing Images.

Edge detection of ground objects is a typical task in the field of remote sensing and has advantages in accomplishing many complex ground object extraction tasks. Although recent mainstream edge detection methods based on deep learning have significant effects, these methods have a very high dependence on the quantity and quality of samples. Moreover, using datasets from other domains in detection tasks often leads to degraded network performance due to variations in the ground objects in different regions. If this problem can be solved to allow datasets from other domains to be reused, the number of labeled samples required in the new task domain can be reduced, thereby shortening the task cycle and reducing task costs. In this paper, we propose a weakly supervised domain adaptation method to address the high dependence of edge extraction networks on samples. The domain adaptation is performed on the edge level and the semantic level, which prevents deviations in the semantic features that are caused by the overgeneralization of edge features. Additionally, the effectiveness of our proposed domain adaptation module is verified. Finally, we demonstrate the superior edge extraction performance of our method in the SEGOS edge extraction network in contrast to other edge extraction methods.

Combined use of interferon alpha-1b, interleukin-2, and thalidomide to reverse the AML1-ETO fusion gene in acute myeloid leukemia.

This study aims to explore the effect of the ITI (interferon alpha-1b, thalidomide, and interleukin-2) regimen on the AML1-ETO fusion gene in patients with t(8;21) acute myeloid leukemia (AML) who were in hematologic remission but positive for the AML1-ETO fusion gene. From September 2014 to November 2020; 20 patients with AML (15 from The Affiliated Cancer Hospital of Zhengzhou University, 4 from The First Affiliated Hospital; and College of Clinical Medicine of Henan University of Science and Technology, and 1 from Anyang District Hospital) with hematological remission but AML1-ETO fusion gene positivity were treated with different doses of the ITI regimen to monitor changes in AML1-ETO fusion gene levels. Twenty patients were treated with a routine dose of the ITI regimen, including 13 males and 7 females. The median patient age was 38 (14-70 years). The fusion gene was negative in 10 patients after 1 (0.5 ~ 8.6) month, significantly decreased in 4 patients after 2.8 (1 ~ 6) months, increased in 4 patients, and unchanged in 2 patients. The 4 patients with elevated levels of the fusion gene were treated with an increased dose of the ITI regimen, and all four patients became negative, for a total effective rate of 90%. The ITI regimen reduces AML1-ETO fusion gene levels in patients with AML who are in hematologic remission but are fusion gene-positive. Improvement was observed in patients' response to a higher dose administration, and patients tolerated the treatment well.

Design, synthesis and nematicidal activitives of trifluorobutene amide derivatives against Meloidogyne incognita.

Plant parasitic nematodes have always been a pressing problem in the field of plant protection. Well-established chemical nematicides, especially organophosphorus and carbamates are the most used products for nematode control worldwide. Due to long-term overuse, they have developed serious resistance and new innovative solutions are urgently required. In this study, thirty-one novel trifluorobutene amide derivatives were designed and synthesized, and their nematicidal activities were determined. Three different synthetic methods have been developed for the final amidation reaction enabling the successfully syntheses of the target compounds independently from the nucleophilicities of the substrate amino group. Most target compounds showed good nematicidal activity in our in vitro test. Among all the compounds, compounds A8 and A23 exhibited excellent nematicidal activity against Meloidogyne incognita, their LC50 values are 2.02 mg L-1 and 0.76 mg L-1, respectively. In particular, compound A23 has found to be almost as active as the commercial nematicide fluensulfone. Furthermore, most compounds gave full control (100% inhibition) of M. incognita at 40 mg L-1 in the in vivo tests in sandy soil, the best compounds were further investigated for in vivo activity in matrix soil. Among the compound tested, compound A8 showed excellent in vivo nematicidal activity. At a concentration of 5 mg L-1 still 56% inhibition was observed. The results of our study indicate that compound A8 possesses excellent in vitro and in vivo nematicidal activity, and can be considered as promising lead molecule for further modification.

Characteristics and Evolution of Nitrogen in the Heavy Components of Algae Pyrolysis Bio-Oil.

Algae pyrolytic bio-oil contains a large quantity of N-containing components (NCCs), which can be processed as valuable chemicals, while the harmful gases can also be released during bio-oil upgrading. However, the characteristics of NCCs in the bio-oil, especially the composition of heavy NCCs (molecular weight ≥200 Da), have not been fully studied due to the limitation of advanced analytical methods. In this study, three kinds of algae rich in lipids, proteins, and carbohydrates were rapidly pyrolyzed (10-25 °C/s) at different temperatures (300-700 °C). The bio-oil was analyzed using a Fourier transform ion cyclotron resonance mass spectrometer equipped with electrospray ionization, and the characteristics and evolution of nitrogen in heavy components were first obtained. The results indicated that the molecular weight of most heavy NCCs was distributed in the 200-400 Da range. N1-3 compounds account for over 60% in lipid and protein-rich samples, while N0 and N4 components are prominent in carbohydrate-rich samples. As temperature increases, most NCCs become more aromatic and contain less O due to the strong Maillard and deoxygenation reactions. Moreover, the heavier NCCs were promoted to form lighter compounds with more nitrogen atoms through decomposition (mainly denitrogenation and deoxygenation). Finally, some strategies to deal with the NCCs for high-quality bio-oil production were proposed.

Potential role of Candida albicans secreted aspartic protease 9 in serum induced-hyphal formation and interaction with oral epithelial cells.

INTRODUCTION: Candida albicans possesses the ability to switch rapidly between yeast to hyphal forms. Hyphal formation is a remarkable pathogenic characteristic, which allows C. albicans to invade into host cells. OBJECTIVES: This study was to investigate the role of the C. albicans SAP9 gene in hyphal formation and invasion ability. METHODS: The morphology of fungal cells in the hyphal-inducing liquid media (YPD+10% fetal bovine serum) was observed by the microscopy. And the morphology of the colony on solid agar plates of YPD+10% fetal bovine serum was photographed by the digital camera. The mRNA expressions of hypha-associated genes in serum medium were also analyzed by real time PCR. Then for the interaction between C. albicans and oral epithelial cells, endocytosis essay, invasion essay and damage assay were performed to compare the differences between the sap9Δ/Δ mutant strain and wild type strain. RESULTS: Compared with the wild type strain, the sap9Δ/Δ mutant strain exhibited a deficient yeast-to-hyphal morphological transition under serum hyphal-inducing conditions. Furthermore, the SAP9 knockout strain revealed a significant down-regulation of the expression of EFG1 (~40%), which is a transcription factor gene that mediates hyphae formation in C. albicans. Compared with the wild type strain, a 70% reduction in the endocytosis of the sap9Δ/Δ mutant strain by host cells was observed, as well as a 25% attenuation of active penetration and a 40% attenuation of host cell damage (P <0.05). CONCLUSIONS: Our data strongly suggests that C. albicans Sap9 is a potential hyphal-associated factor that responds to serum hyphal-inducing stimuli via a cAMP-protein kinase A pathway mediated by EFG1, and contributes to the process of invasion of Candida into the epithelial cells, leading to host cell damage.

[Development of a cell-based diagnostic system for vitamin K-dependent coagulation factor deficiency 1].

OBJECTIVE: To develop a cell-based system for the diagnosis of vitamin K-dependent coagulation factor deficiency 1 (VKCFD1). METHODS: In HEK293 cells stably expressing the reporter gene FIX-Gla-PC, the gamma-glutamyl carboxylase (GGCX) gene was knocked out by using CRISPR/Cas9 technology. Enzyme-linked immunosorbent assay (ELISA), DNA sequencing and Western blotting were used to identify the GGCX gene knockout cells. A quickchange point variant method was used to construct the GGCX variant. ELISA was used to assess the influence of GGCX variant on the activity of reporter gene. RESULTS: Two monoclonal cell lines with no reporter activity by ELISA was identified. Edition and knockout of the GGCX gene was confirmed by DNA sequencing and Western blotting. The activity of the reporter gene was recovered by transfection of the wild-type GGCX gene. Thereby two monoclonal cells with GGCX knockout were obtained. By comparing the wild-type and pathogenic GGCX variants, the reporter activity was decreased in the pathogenic variants significantly. CONCLUSION: A cell-based system for the detection of GGCX activity was successfully developed, which can be used for the diagnosis of VKCFD1 caused by GGCX variants.

A pilot study: a possible implication of Candida as an etiologically endogenous pathogen for oral lichen planus.

BACKGROUND: The aim of this study was to investigate the prevalence and genotypic profiles of Candida albicans in patients with oral lichen planus (OLP). MATERIALS AND METHODS: Positive rates and genotypic profiles of Candida albicans strains from OLP patients and healthy controls were analyzed. Random amplified polymorphic DNA and internal transcribed spacer of ribosome DNA polymerase chain reactions were used to sequence the DNA of these strains, and then their genetic similarity was measured using BLAST, UIV Band, and Vector NTI Suite Sequence Analyses Software. RESULTS: The prevalence of C. albicans strains detected from erosive-OLP, non-erosive OLP, and normal individuals was 18.87, 18.75, and 7.92%, respectively. Four different genotypes were revealed by the two methods. To be specific, type I was found only in the healthy subjects; type II a and II b were found in non-erosive OLP, and type III was identified in erosive OLP. Intragroup similarity coefficients, i.e. SAB were 100%, and inter-groups similarity coefficients, i.e. SAB were less than 30%. CONCLUSIONS: The genotypic results of C. albicans in OLP revealed an endogenous rather than exogenous infection of C. albicans. In addition, a possible pathogenic role of C. albicans in OLP, with the etiologic sense contributing to a more proper recognition on the pathogenesis, development, and progression of OLP, as well as some strategies for its diagnosis and treatment were identified.