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The low utilization efficiency of nitrogen fertilizer in agricultural ecosystem has caused serious economic and environmental issues. Dicyandiamide (DCD) is a widely used nitrification inhibitor, which can inhibit nitrification via affecting ammonia oxidizing microorganisms with minimal influence on other soil microorganisms, thereby reducing the leaching of nitrate and emission of greenhouse gases. The factors influencing the efficiency of DCD in soil include soil temperature, pH, texture, organic matter, moisture, etc. Recently, the application of molecular methods in agricultural systems has shed new light on the microbial mechanism underlying nitrification inhibition by DCD. In this review, the enzymatic inhibition mechanism, the application effects and their influence factors of DCD were summarized, and the prospects of its application were discussed as well.

Objective: To explore differences in bone marrow angiogenesis seen in aplastic anemia (AA) patients presenting with differential Chinese medicine (CM) syndrome, and to correlate these differences with clinical pathology., Methods: Thirty-five patients were enrolled, including 18 with "yang deficiency syndrome" and 17 with "yin deficiency syndrome." Bone marrow biopsies and serum were collected. Microvessel density (MVD) and positive expression of vascular endothelial-derived growth factor (VEGF) were detected by immunohistochemisty. Hypoxia inducible factor -1α (HIF-1α), and VEGF expression were assayed by enzyme-linked immunoabsorbent assay (ELISA), serum lactate dehydrogenase (LDH) was tested by enzyme method and liquid chip technology was used to detected the expression of interleukin (IL)-2, IL-4, IL-6, IL-10, interferon (IFN)-γ and tumor necrosis factor (TNF)-α., Results: Counts for leukocytes, absolute neutrophils and platelets in "yin deficiency syndrome" were lower than those found in "yang deficiency syndrome" (P<0.05). MVD and VEGF expression, and the positive rate of CD34 and VEGF in bone marrow were lower in AA, especially in "yin deficiency syndrome" (P<0.01 or P<0.05). "Yin deficiency syndrome" displayed decreased VEGF and LDH expression, and enhanced expression of HIF-1α as compared to "yang deficiency syndrome" (P<0.05). Levels of IL-4 and IL-6 were higher in AA (P<0.01), but IL-10 was decreased (P<0.05). High TNF-α expression was seen in "yang deficiency syndrome" and IFN-γ expression was decreased in "yin deficiency syndrome" as compared with normals (P <0.01 and P<0.05, respectively)., Conclusion: AA patients have lower MVD than normals, especially in "yin deficiency syndrome." MVD might differentially correlate to disease severity, and could be dependent on bone marrow or serum VEGF expression and LDH. Additionally, IL-2, IL-10, IL-4 and IFN-γ were negatively associated while IL-6 and TNF-α were positively associated with MVD.

Background: Appendiceal mucinous neoplasms (AMNs) with disseminated disease (pseudomyxoma peritonei) are heterogeneous tumors with variable clinicopathologic behavior. Despite the development of prognostic systems, objective biomarkers are needed to stratify patients. With the advent of next-generation sequencing (NGS), it remains unclear if molecular testing can improve the evaluation of disseminated AMN patients., Methods: Targeted NGS was performed for 183 patients and correlated with clinicopathologic features to include American Joint Committee on Cancer/World Health Organization (AJCC/WHO) histologic grade, peritoneal cancer index (PCI), completeness of cytoreduction (CC) score, and overall survival (OS)., Results: Genomic alterations were identified for 179 (98%) disseminated AMNs. Excluding mitogen-activated protein kinase genes and GNAS due to their ubiquitous nature, collective genomic alterations in TP53, SMAD4, CDKN2A, and the mTOR genes were associated with older mean age, higher AJCC/WHO histologic grade, lymphovascular invasion, perineural invasion, regional lymph node metastasis, and lower mean PCI (p < 0.040). Patients harboring TP53, SMAD4, ATM, CDKN2A, and/or mTOR gene alterations were found to have lower OS rates of 55% at 5 years and 14% at 10 years, compared with 88% at 5 years and 88% at 10 years for patients without the aforementioned alterations (p < 0.001). Based on univariate and multivariate analyses, genomic alterations in TP53, SMAD4, ATM, CDKN2A, and/or the mTOR genes in disseminated AMNs were a negative prognostic factor for OS and independent of AJCC/WHO histologic grade, PCI, CC score, and hyperthermic intraperitoneal chemotherapy treatment (p = 0.006)., Conclusions: Targeted NGS improves the prognostic assessment of patients with disseminated AMNs and identifies patients who may require increased surveillance and/or aggressive management., (© 2023. Society of Surgical Oncology.)

Many forms of cancer have multiple subtypes with different causes and clinical outcomes. Somatic tumor genome sequences provide a rich new source of data for uncovering these subtypes but have proven difficult to compare, as two tumors rarely share the same mutations. Here we introduce network-based stratification (NBS), a method to integrate somatic tumor genomes with gene networks. This approach allows for stratification of cancer into informative subtypes by clustering together patients with mutations in similar network regions. We demonstrate NBS in ovarian, uterine and lung cancer cohorts from The Cancer Genome Atlas. For each tissue, NBS identifies subtypes that are predictive of clinical outcomes such as patient survival, response to therapy or tumor histology. We identify network regions characteristic of each subtype and show how mutation-derived subtypes can be used to train an mRNA expression signature, which provides similar information in the absence of DNA sequence.

Background: Dapsone is used in the treatment of infections and inflammatory diseases. The dapsone hypersensitivity syndrome, which is associated with a reported mortality of 9.9%, develops in about 0.5 to 3.6% of persons treated with the drug. Currently, no tests are available to predict the risk of the dapsone hypersensitivity syndrome., Methods: We performed a genomewide association study involving 872 participants who had received dapsone as part of multidrug therapy for leprosy (39 participants with the dapsone hypersensitivity syndrome and 833 controls), using log-additive tests of single-nucleotide polymorphisms (SNPs) and imputed HLA molecules. For a replication analysis, we genotyped 24 SNPs in an additional 31 participants with the dapsone hypersensitivity syndrome and 1089 controls and performed next-generation sequencing for HLA-B and HLA-C typing at four-digit resolution in an independent series of 37 participants with the dapsone hypersensitivity syndrome and 201 controls., Results: Genomewide association analysis showed that SNP rs2844573, located between the HLA-B and MICA loci, was significantly associated with the dapsone hypersensitivity syndrome among patients with leprosy (odds ratio, 6.18; P=3.84×10(-13)). HLA-B*13:01 was confirmed to be a risk factor for the dapsone hypersensitivity syndrome (odds ratio, 20.53; P=6.84×10(-25)). The presence of HLA-B*13:01 had a sensitivity of 85.5% and a specificity of 85.7% as a predictor of the dapsone hypersensitivity syndrome, and its absence was associated with a reduction in risk by a factor of 7 (from 1.4% to 0.2%). HLA-B*13:01 is present in about 2 to 20% of Chinese persons, 1.5% of Japanese persons, 1 to 12% of Indians, and 2 to 4% of Southeast Asians but is largely absent in Europeans and Africans., Conclusions: HLA-B*13:01 was associated with the development of the dapsone hypersensitivity syndrome among patients with leprosy. (Funded by the National Natural Science Foundation of China and others.).

Land use management, one of the most important aspects of anthropogenic disturbance to terrestrial ecosystems, has exerted overriding impacts on soil biogeochemical cycling and inhabitant microorganisms. However, the knowledge concerning response of different archaeal groups to long-term land use changes is still limited in terrestrial environments. Here we used quantitative polymerase chain reaction (qPCR) and denaturing gradient gel electrophoresis (DGGE) approaches to investigate the response of archaeal communities to four different land use practices, i.e. cropland, pine forest, restoration land and degradation land. qPCR analyses showed that expression of the archaeal amoA gene responds more sensitively to changes of land use. In particular, we observed, occurring at significantly lower numbers of archaeal amoA genes in degradation land samples, while the abundance of total archaea and Group 1.1c based on 16S rRNA gene copy numbers remained constant among the different treatments examined. Soil nitrate content is significantly correlated with archaeal amoA gene abundance, but not their bacterial counterparts. The percentage of archaea among total prokaryote communities increases with increasing depth, but has no significant relationship with total carbon, total nitrogen or pH. Soil pH was significantly correlated with total bacterial abundance. Based on results from PCR-DGGE, three land use practices (i.e. cropland, pine forest, restoration land) showed distinct dominant bands, which were mostly affiliated with Group 1.1a. Degradation land, however, was dominated by sequences belonging to Group 1.1c. Results from this study suggest that community structure of ammonia oxidizing archaea were significantly impacted by land use practices., (Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.)

Casein kinase I alpha (CK1α) is a member of serine/threonine protein kinase, generally present in all eukaryotes. In mammals, CK1α regulates the transition from interphase to metaphase in mitosis. However, little is known about its role in meiosis. Here we examined Ck1α mRNA and protein expression, as well as its subcellular localization in mouse oocytes from germinal vesicle to the late 1-cell stage. Our results showed that the expression level of CK1α was increased in metaphase. Immunostaining results showed that CK1α colocalized with condensed chromosomes during oocyte meiotic maturation and early embryo development. We used the loss-of-function approach by employing CK1α specific morpholino injection to block the function of CK1α. This functional blocking leads to failure of polar body 1 (PB1) extrusion, chromosome misalignment and MII plate incrassation. We further found that D4476, a specific and efficient CK1 inhibitor, decreased the rate of PB1 extrusion. Moreover, D4476 resulted in giant polar body extrusion, oocyte pro-MI arrest, chromosome congression failure and impairment of embryo developmental potential. In addition, we employed pyrvinium pamoate (PP), an allosteric activator of CK1α, to enhance CK1α activity in oocytes. Supplementation of PP induced oocyte meiotic maturation failure, severe congression abnormalities and misalignment of chromosomes. Taken together, our study for the first time demonstrates that CK1α is required for chromosome alignment and segregation during oocyte meiotic maturation and early embryo development.

Objective: To examine the relationship between sex hormone-binding globulin (SHBG) and the metabolic syndrome (MetS) in pre-elderly and elderly men in China., Methods: A cross-sectional study was done among 437 men, aged 45 to 94 years old. Early morning fasting sera were assayed for total testosterone (TT), SHBG and other biochemical markers. Free testosterone (FT) was calculated., Results: The SHBG level of the MetS group was significantly lower than those without MetS 35.70 (25.18, 47.10) nmol/L vs. 41.90 (31.80, 55.20) nmol/L; P < 0.001). As the number of MetS components increases, SHBG and TT levels became lower. SHBG correlated with age, as did TT and most of metabolic components. Body mass index (BMI), high density lipoprotein-cholesterol (HDL-C), triglyceride (TG), and TT remained independently associated with SHBG by multivariate regression analysis. In a logistic regression taking MetS as the dependent variable, SHBG (95% confidence interval (95% CI): 0.975-0.994, P = 0.018) and homeostasis model assessment for insulin resistance (HOMA-IR) (95%CI: 1.535-2.647, P < 0.001) were included in the final model., Conclusions: Lower SHBG is independently associated with MetS among pre-elderly and elderly men. SHBG may be an independent predictor of MetS, but the mechanism of how SHBG is involved in MetS requires further studied.

Cervical cancer ranks as the fourth most common and fatal cancer among women worldwide. Studies have demonstrated a strong association between purinergic platelet signaling and tumor progression in this type of cancer. The literature shows that neoplastic cells, when in the bloodstream, secrete adenosine triphosphate (ATP) and adenosine nucleotide diphosphate (ADP) that act on their corresponding platelet P2Y and P2X receptors. The interaction of these nucleotides with their receptors results in platelet activation and degranulation, ensuing several consequences, such as vascular endothelial growth factor (VEGF), platelet-derived growth factor, matrix metalloproteinases, ADP, and ATP. These molecules play essential roles in angiogenesis and tumor metastasis in cervical cancer. Several purinergic receptors are found in endothelial cells. Their activation, especially P2Y2, by the nucleotides released by platelets can induce relaxation of the endothelial barrier and consequent extravasation of tumor cells, promoting the development of metastases. Cancer cells that enter the bloodstream during the metastatic process are also subject to high shear stress and immune surveillance. In this context, activated platelets bind to circulating tumor cells and protect them against shear stress and the host's immune system, especially against natural killer cells, facilitating their spread throughout the body. Furthermore, activation of the P2Y12 receptor present on the platelet surface promotes the release of VEGF, the main inducer of angiogenesis in cervical cancer, in addition to increasing the concentration of several other pro-angiogenic molecules. Therefore, this review will address the role of platelet purinergic signaling in tumor progression of cervical cancer and propose possible therapeutic targets. [ABSTRACT FROM AUTHOR]

To modify the physical features and extend applications of the 3-nitro-1,2,4-triazol-5-one (NTO), we synthesized NTO with acridine (ACR) at a molar ratio of 1:1, a neutralization reaction. Through altering the chemical composition, it was possible to alter physical properties such as thermal stability, free space (voids), packing coefficient, crystal density, difference in pKa of co-formers, morphology, solubility, and impact sensitivity, and detonation parameters. It appears that physical attributes could be entirely altered. Single-crystal and powder X-ray diffraction methods, infrared spectroscopy, mass spectrometry, nuclear magnetic resonance spectroscopy (1H-NMR and 13C-NMR), and thermal analysis were utilized to comprehensively characterize and confirm the formation of the structure of NTO:ACR. The substantial hydrogen bond interactions and planar layered structures observed between the cations and anions generated a complex 3D network, providing insight into the structure–property interrelationship. One intriguing feature discovered is the layered structure present in NTO:ACR, which may be responsible for the low impact sensitivity. According to the experimental results, NTO:ACR showed good thermal stability (Td = 229 °C) and outstanding impact sensitivity (IS = 100 J). Detonation velocity and pressure were calculated using the EXPLO5 software program and found to be 7006 m·s−1 and 20.02 GPa, respectively. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of homoharringtonine (HHT) on leukemic stem-like cells (LSC) in human acute myeloid leukemia (AML) cell lines., Methods: The phenotypes of AML cell lines U937,Kasumi-1,and KG-1 cells were analyzed by flow cytometry (FACS). The effect of HHT on leukemia stem-like cells with immunophenotype of CD34(+)CD38(-)CD96(+) was detected with FACS. Cell growth was measured by MTT assay. Activation of Caspase pathway and expression of apoptosis-related regulator proteins were examined by Western blotting., Results: FACS demonstrated that the 69% of KG-1 cells expressed LSC phenotype CD34(+)CD38(-)CD96(+), while 26.7% on Kasumi-1 cells expressed this marker. In contrast,U937 cells showed CD96 negative. HHT significantly inhibited cell growth of KG-1 cells with an IC(50) of 16.9 ng/ml at 48 h. The ratio of CD34(+)CD38(-)CD96(+) cells decreased from 63.6% to 17.1% after HHT treatment. Enhanced apoptosis was demonstrated in HHT group evidenced by strong activation of Caspase-9,Caspase-3 and PARP.HHT treatment resulted in down-regulation of expression of anti-apoptotic protein BCL-2 and phosphorylated-Akt., Conclusion: HHT can effectively kill the leukemic stem-like cells in human AML cell line KG1 by inhibiting cell growth and inducing apoptosis which is associated with activation of Caspase pathway and down-regulation of anti-apoptotic proteins and phosphorylated-Akt.

Archaea, as the third life form distinct from bacteria and eukaryota, widely distribute in various kinds of habitats, and play important roles in the biogeochemical cycles of carbon and nitrogen and in ecosystem functioning. As the biomarker of archaea, archaeal membrane lipids can be used to investigate the archaeal community composition and its responses to the environment. This paper introduced the structural characteristics of archaeal membrane lipids and the differences in the membrane lipids composition among different archaeal communities, and discussed the feasibility of using archeal membrane lipids in depicting archaeal community composition. The abundance of archaeal membrane lipids in the environment could be used to characterize the biomass of archaea, and the related results could complement and ascertain each other with the DNA-based bio-molecular approaches on the accuracy, analysis efficiency, and cost. Based on the description of the difficulties and importance of using archaeal membrane lipids to analyze the composition and abundance of archaeal communities, and by linking to the environmental factors such as temperature and pH that affected the archaeal community composition, the relationships between archaea and their habitats were further expatiated, and the evolution process of archaeal communities and its application prospects in the studies of geochemistry and geological events were analyzed.

Ammonia (NH(3)) oxidation, the first and rate-limiting step of nitrification, is a key step in the global Nitrogen (N) cycle. Major advances have been made in recent years in our knowledge and understanding of the microbial communities involved in ammonia oxidation in a wide range of habitats, including Chinese agricultural soils. In this mini-review, we focus our attention on the distribution and community diversity of ammonia-oxidizing bacteria (AOB) and ammonia oxidizing archaea (AOA) in Chinese soils with variable soil properties and soil management practices. The niche differentiation of AOB and AOA in contrasting soils have been functionally demonstrated using DNA-SIP (stable isotope probing) methods, which have shown that AOA dominate nitrification processes in acidic soils, while AOB dominated in neutral, alkaline and N-rich soils. Finally, we discuss the composition and activity of ammonia oxidizers in paddy soils, as well as the mitigation of the greenhouse gas nitrous oxide (N(2)O) emissions and nitrate leaching via inhibition of nitrification by both AOB and AOA.

Calorie restriction (CR) is a simple method for delaying aging process, extending lifespan, and preventing the onset of aging-related diseases, such as diabetes. However, the mechanism, by which CR influences β-cell functions during the aging process, still remains unclear. In this study, sixteen 8-week-old male Sprague-Dawley rats were randomized to control group with food intake ad libitum and CR group fed with 70% of food intake of the control group. Twenty-four weeks later, the body weights of the rats with CR were significantly lower with the smaller amounts of perirenal and epididymal fats, compared to those of control rats. The β-cell activity, as judged by the early insulin secretion in the intraperitoneal glucose tolerance test, was significantly higher in the CR group than that in control animals. Moreover, CR animals showed the increased β-cell mass and proliferation of β-cells in pancreas. The plasma level of malondialdehyde was lower in CR rats than that in control rats, while the activities of superoxide dismutase, catalase and glutathione peroxidase in plasma were higher in CR rats than control rats. These results indicate that aging is associated with the increases in oxidative stress, which was, however, alleviated by CR. In conclusion, CR from a young age preserves the principal β-cell function of early insulin secretion in rats probably by stimulating the β-cell proliferation. Our observations provide the evidence for clinical significance of CR in preventing β-cell dysfunction during the aging process, which may delay the onset of aging-related disease, including diabetes in humans.

Increasing evidence demonstrated the involvement of ammonia-oxidizing archaea (AOA) in the global nitrogen cycle, but the relative contributions of AOA and ammonia-oxidizing bacteria (AOB) to ammonia oxidation are still in debate. Previous studies suggest that AOA would be more adapted to ammonia-limited oligotrophic conditions, which seems to be favored by protonation of ammonia, turning into ammonium in low-pH environments. Here, we investigated the autotrophic nitrification activity of AOA and AOB in five strongly acidic soils (pH<4.50) during microcosm incubation for 30 days. Significantly positive correlations between nitrate concentration and amoA gene abundance of AOA, but not of AOB, were observed during the active nitrification. (13)CO(2)-DNA-stable isotope probing results showed significant assimilation of (13)C-labeled carbon source into the amoA gene of AOA, but not of AOB, in one of the selected soil samples. High levels of thaumarchaeal amoA gene abundance were observed during the active nitrification, coupled with increasing intensity of two denaturing gradient gel electrophoresis bands for specific thaumarchaeal community. Addition of the nitrification inhibitor dicyandiamide (DCD) completely inhibited the nitrification activity and CO(2) fixation by AOA, accompanied by decreasing thaumarchaeal amoA gene abundance. Bacterial amoA gene abundance decreased in all microcosms irrespective of DCD addition, and mostly showed no correlation with nitrate concentrations. Phylogenetic analysis of thaumarchaeal amoA gene and 16S rRNA gene revealed active (13)CO(2)-labeled AOA belonged to groups 1.1a-associated and 1.1b. Taken together, these results provided strong evidence that AOA have a more important role than AOB in autotrophic ammonia oxidation in strongly acidic soils.

To understand the distribution and diversity of archaea in Chinese soils, the archaeal communities in a series of topsoils and soil profiles were investigated using quantitative PCR, T-RFLP combining sequencing methods. Archaeal 16S rRNA gene copy numbers, ranging from 4.96 × 10(6) to 1.30 × 10(8)  copies g(-1) dry soil, were positively correlated with soil pH, organic carbon and total nitrogen in the topsoils. In the soil profiles, archaeal abundance was positively correlated with soil pH but negatively with depth profile. The relative abundance of archaea in the prokaryotes (sum of bacteria and archaea) ranged from 0.20% to 9.26% and tended to increase along the depth profile. T-RFLP and phylogenetic analyses revealed that the structure of archaeal communities in cinnamon soils, brown soils, and fluvo-aquic soils was similar and dominated by Crenarchaeota group 1.1b and 1.1a. These were different from those in red soils, which were dominated by Crenarchaeota group 1.3 and 1.1c. Canonical correspondence analysis indicated that the archaeal community was primarily influenced by soil pH., (© 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.)

Objective: To probe the effects of qi-supplementing and yin-nourishing therapy (blood-increasing decoction and blood generating powder) on chronic thrombocytopenia., Methods: Two hundred patients with chronic thrombocytopenia were randomly divided into control (n = 100) and test groups (n = 100) with Amino-polypeptide as a basic treatment for both. Test group patients consumed a blood-increasing decoction and blood-generating powder for 1-3 months. Improvements in platelet counts and TCM syndrome were observed., Results: One hundred and sixty-four (80 in the test group and 84 in the control group) of 189 total participants were treated for 3 months. The total effective rate in improving TCM syndrome was 95.00% in the test group and 79.76% in the control group (P < 0.05). There was significant difference (P < 0.05) in the accumulated score of TCM syndrome between the two groups treated at different time points. The total effective rate of platelet counts was 86.25% in the test group and 59.52% in the control group (P < 0.05). There was a significant difference in platelet counts before and after treatment in the two groups (P < 0.05). There was no significant differences in platelet count between the two groups treated for 1-2 months; however, a significant difference was found between the two groups after treatment for 3 months (P < 0.05)., Conclusions: After a 3-month treatment of chronic thrombocytopenia patients with qi-supplementing and yin-nourishing therapy, TCM syndrome was improved and platelet counts increased with no obvious side effects, and the quality of life of the participants was enhanced with noticeable long-term curative effects.

Eukaryota, bacteria and archaea are the three domains of life. As the third domain of life, archaea has been found not only in extreme environments such as high-temperature, high-saline, and extremely acid habitats, but also in moderate environments including ocean, lake and soil, which implies that archaea may contribute greatly to various ecosystems. By targeting the 16S rRNA gene with real-time PCR approaches, this paper studied the abundance of archaea, crenarchaea and bacteria from two agricultural soil profiles and two long-term fertilization stations Qiyang (QY) and Fengqiu (FQ). The 16S rRNA gene copy number of crenarchaea was 1-2 orders of magnitude lower than that of archaea, and the order of these three groups was crenarchaea < archaea < bacteria. The ratios of both archaea and crenarchaea to bacteria increased with soil depth. The abundance of archaea and crenarchaea had significantly different responses to different fertilization treatments. In QY station, the copy numbers of archaeal and bacterial 16S rRNA gene had significant positive correlations with soil pH (r = 0.850, P < 0.01 and r = 0.676, P < 0.05, respectively); in FQ station, all the 16S rRNA gene copy numbers of archaea, crenarchaea and bacteria had no significant correlations with soil pH, but significantly correlated with soil organic matter (r = 0.783, P < 0.05; r = 0. 827, P < 0.05; r = 0.767, P < 0.05, respectively). To understand the distribution of archaea and crenarchaea in agricultural soil could provide important information to evaluate their ecological functions in soil ecosystem and element cycling.

Purpose: Denitrification is an important biochemical process in global nitrogen cycle, with a potent greenhouse gas product N(2)O. Wastewater irrigation can result in the changes of soil properties and microbial communities of agricultural soils. The purpose of this study was to examine how the soil denitrification genes responded to different irrigation regimes., Materials and Methods: Soil samples were collected from three rural districts of Beijing (China) with three different irrigation regimes: clean groundwater (CW), reclaimed water (RW), and wastewater (WW). The abundance and diversity of three denitrification microbial genes (nirS, nirK, and nosZ) were examined by real-time polymerase chain reaction (PCR) and denaturing gradient gel electrophoresis (DGGE) molecular approaches., Results and Discussion: The abundance of nirS in the WW treatment was higher than that in the CW treatment, and no significant difference was found between the RW and CW or WW treatments. The abundance of nirK gene of the RW and WW treatments was higher than that of the CW treatment. There was no difference for nosZ gene among the three treatments. Correspondence analysis based on the DGGE profiles showed that there was no obvious difference in the nosZ gene composition, but nirS and nirK genes changed with different irrigation regimes., Conclusions: Irrigation with unclean water sources enhanced the soil NO (3) (-) content and changed the abundance and composition of soil denitrifiers, and different functional genes had different responses. Irrigation with unclean water sources increased the abundance of nirK gene and changed the community structures of nirS and nirK genes, while nosZ gene was relatively stable in the soil. These results could be helpful to explore the mechanisms of the variation of denitrification processes under long-term wastewater irrigation and partially explain the reason of more N(2)O output in the field with wastewater irrigation.

Objective: To analyze the current situation and prevalence of leprosy in Wenshan district, Yunnan province., Methods: To collect various data on leprosy reported by the health workers at the county level., Results: The number of newly registered patients did not decrease significantly in 1989, 1999 and 2009, respectively. The mean age of patients at detection was 33 - 35 years old. Time of delay between the disease onset and being diagnosed was shortened from 35.2 months in 1989 to 15.9 months in 2009. However, the proportion of patients with more than 12 months of delay still accounted for nearly 50%. The proportion of Grade II disability fluctuated between 15.2% - 17.7% and the proportion of child cases increased from 8.1% in 1989 to 13.1% in 2009. Clinics for skin diseases were the main locations for case detection. The proportion of new cases detected through 'active case finding' program accounted for 44.3% in 1999 and 42.6% in 2009, both higher than 17.7% in 1989., Conclusion: The situation of leprosy in Wenshan district, Yunnan province, was still serious and the reason for the occurrence of new cases was related to the fact that the infectious source of leprosy had not been under full control.

Objective: To study the epidemiological characteristics of leprosy and to provide evidence for specific strategies development on leprosy control., Methods: Descriptive analysis of data from the national leprosy surveillance system was carried out in 2009., Results: A total number of 1597 new cases were detected in 2009 with a case detection rate of 0.120 per 100 000 population. The proportions of children under 15, multibacillary and disability grade 2 were 2.4%, 84.3% and 22.8% respectively. A total number of 148 relapse cases were reported in 2009, among which 69 cases were those relapsed after multi-drug therapy. The existing cases were 6603 by the end of 2009 with a prevalence rate of 0.049 per 10 000 populations, among which 3332 cases were on multi-drug therapy., Conclusion: The overall leprosy situation is considered to be at low endemic in China but the distribution is unequal, with pocket areas in Yunnan, Sichuan and Guizhou. In order to reach the target on leprosy elimination, which was considered as a public health and social problem, the input and efforts are needed for many years to come.

The worldwide burden of sickle cell disease is enormous, with over 200,000 infants born with the disease each year in Africa alone. Induction of fetal hemoglobin is a validated strategy to improve symptoms and complications of this disease. The development of targeted therapies has been limited by the absence of discrete druggable targets. We developed a unique bead-based strategy for the identification of inducers of fetal hemoglobin transcripts in primary human erythroid cells. A small-molecule screen of bioactive compounds identified remarkable class-associated activity among histone deacetylase (HDAC) inhibitors. Using a chemical genetic strategy combining focused libraries of biased chemical probes and reverse genetics by RNA interference, we have identified HDAC1 and HDAC2 as molecular targets mediating fetal hemoglobin induction. Our findings suggest the potential of isoform-selective inhibitors of HDAC1 and HDAC2 for the treatment of sickle cell disease.

Purpose: Experiments were conducted to examine the effects of mercury (Hg) on soil nitrification activities and the microbial communities of ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA)., Methods: The soil samples spiked with different Hg concentrations were incubated for a period of 1, 2, 4, and 8 weeks in triplicate and the potential nitrification rate (PNR) of the samples was determined. The abundance of AOB and AOA was measured after an 8-week incubation by real-time polymerase chain reaction (PCR) assay of the amoA genes, while the community compositions by cloning and sequencing approaches., Results: The soil PNR differed with different incubation periods. It tended to decrease with increasing soil Hg concentrations at week 1, basing on which the half-maximal effective concentration (EC50) was 1.59 mg kg(-1). There was no significant difference in the abundance of AOB or AOA among the treatments. The AOB community was dominated by Nitrosospira-like sequences and more than 70% of the obtained clones were affiliated with the cluster 3a.2. The percentage of cluster 3a.1 in AOB community appeared to a consistent trend of decreasing with ascending soil Hg concentrations. While all the AOA sequences in the clone libraries were grouped into cluster S (soil and sediment origin)., Conclusions: This study revealed that Hg could inhibit soil potential nitrification and the extent varied with incubation periods. Soil Hg pollution changed the composition of soil AOB to some extent. These findings will be helpful to recognize the effects of Hg on the activity and community composition of soil ammonia oxidizers.

Nitrification is a key process of the nitrogen (N) cycle in soil with major environmental implications. The recent discovery of ammonia-oxidizing archaea (AOA) questions the traditional assumption of the dominant role of ammonia-oxidizing bacteria (AOB) in nitrification. We investigated AOB and AOA growth and nitrification rate in two different layers of three grassland soils treated with animal urine substrate and a nitrification inhibitor [dicyandiamide (DCD)]. We show that AOB were more abundant in the topsoils than in the subsoils, whereas AOA were more abundant in one of the subsoils. AOB grew substantially when supplied with a high dose of urine substrate, whereas AOA only grew in the Controls without the urine-N substrate. AOB growth and the amoA gene transcription activity were significantly inhibited by DCD. Nitrification rates were much higher in the topsoils than in the subsoils and were significantly related to AOB abundance, but not to AOA abundance. These results suggest that AOB and AOA prefer different soil N conditions to grow: AOB under high ammonia (NH(3)) substrate and AOA under low NH(3) substrate conditions.

Objective: To study the therapeutic effect of combined therapy with Chinese drugs and immuno-suppressors, mainly anti-lymphocyte globulin/anti-thymus globulin (ALG/ATG), for the treatment of severe aplastic anemia (SAA), the efficacy associated factors and adverse effects as well., Methods: A retrospective analysis was conducted on 65 patients with SAA treated by combined therapy which was supplemented with cyclosporin A, androgen, hematopoietic growth factor, etc., Results: Of the 57 patients followed-up, 26 (45.6%) were basically cured, 15 (26.3%) remitted, and 8 (14.0%) improved markedly, the total effective rate being 85.9%. By separately comparing with a single item of clinical data, it was shown that the therapeutic effectiveness was correlated, to a certain extent, with age, illness duration, neutrophil count, and bone marrow proliferation in patients before treatment, as well as with infection that occurred in the follow-up period. It was obviously higher in patients with peripheral neutrophil count > 0.5 x 10 10(9)/L (P<0.05). Various degrees of serum sickness-like reactions occurred in the treatment of 36 patients, including fever in 36 (63.2%), skin rash in 8 (14.0%), and musculoskeletal pain in 5 (8.8%)., Conclusions: The therapeutic effect of combined therapy with Chinese drugs and ALG/ATG in treating SAA could be affirmed, showing some superiority as compared with Western medicine alone. The patients' age, duration of illness, neutrophil count, and bone marrow proliferation before treatment, and degree of infection that occurred could affect the therapeutic efficacy to a certain extent. Adverse reactions resulting from the combined therapy are less, showing the toxicity reducing and effect enhancing action of Chinese drugs.

Research on niche specialization in the microbial communities of ammonia oxidizers is important for assessing the consequences of vegetation shift on nitrogen (N) cycling. In this study, soils were sampled from three tree stands (needleleaf, mixed, and evergreen broadleaf) from the Hannam experimental forest in South Korea in spring (May 2019), summer (August 2019), autumn (November 2019), and winter (January 2020). Quantitative polymerase chain reaction (qPCR) and high-throughput sequencing were used to measure the abundance and community structure of various nitrifiers: ammonia-oxidizing archaea and bacteria (AOA and AOB, respectively) as well as complete ammonia oxidizers (comammox). Nitrification rates and total ammonia oxidizer abundance were significantly higher in needleleaf forest soil than those in other forest stands, and they were lowest in evergreen broadleaf forest soil. Comammox clade B was most abundant in needleleaf and evergreen broadleaf forest soils, while AOA were significantly more abundant in mixed forest soil. The abundances of comammox clade B and AOA were negatively correlated with dissolved organic carbon. Phylogenetic analysis showed that NT-alpha and NS-gamma-2.3.2 were the most abundant AOA lineages in all the samples. The seasonal of AOA, AOB, and comammox varied with the sites, suggesting the need to examine the combinations of environmental factors when considering the effects of seasonal changes in the environment. Overall, the results suggest that potential vegetation shifts in forest ecosystems might affect nitrification activities by regulating the abundance and community structure of ammonia oxidizers., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To understand the epidemiological characteristics of leprosy during the evolution of the disease, towards the goal of elimination for the past 50 years and longer, so as to provide experiences for accelerating eradication of leprosy in China., Methods: Data were collected from National Surveillance System of Leprosy which was composed annually of all the data from county-based leprosy unit reporting system. All the data were reviewed retrospectively., Results: A total number of 487 900 leprosy patients were reported from 1949 to 2007 in China. The case detection rate reduced from the highest of 5.56/100 000 in 1958 to the lowest of 0.12/100 000 in 2007. Leprosy patients mainly distributed in mountain areas in Yunnan, Guizhou, Sichuan, Guangdong Guangxi, Hunan and Jiangxi provinces with warm and damp climate and underdeveloped economy. After more than 50 years of leprosy control efforts, the case detection rate declined quickly in provinces in the eastern and the southern parts but very slowly in provinces in the western and the southwestern part of China. The ratio of relapsed patients to newly detected ones increased from 1:139 in 1960s' to 1:10 after 1980s', annually. The proportion of child cases among newly detected patients had been 3% - 4% since 1968. In the recent 20 years, the proportion of new patients with positive skin smear gradually increased and the rate of disability grade two reached 20% and more. The average age of new patients upon diagnosis was 45 years old in the east coastal provinces but only 38 years old in the southwest provinces. A new finding was that some new patients detected in the east coastal provinces were immigrants from the southwestern provinces., Conclusion: With continuous socio-economic development and active efforts on leprosy control, the prevalence of leprosy gradually declined despite the long evolution period. Some negative events seemed to have influenced the trend of case detection.

A sensitive, rapid liquid chromatographic-electrospray ionization mass spectrometric method for the determination of xanthinol in human plasma was developed and validated. Xanthinol nicotinate in plasma (0.5 mL) was pretreated with 20% trichloroacetic acid for protein precipitation. The samples were separated using a Lichrospher silica (5 microm, 250 mm x 4.6 mm i.d.). A mobile phase of methanol-water containing 0.1% formic acid (50: 50, v/v) was used isocratically eluting at a flow rate of 1 mL/min. Xanthinol and its internal standard (IS), acyclovir, were measured by electrospray ion source in positive selected reaction monitoring mode. The method demonstrated that good linearity ranged from 10.27 to 1642.8 ng/mL with r=0.9956. The limit of quantification for xanthinol in plasma was 10.27 ng/mL with good accuracy and precision. The mean plasma extraction recovery of xanthinol was in the range of 90.9-100.2%. The intra- and inter-batch variability values were less than 4.8% and 7.9% (relative standard deviation, R.S.D.), respectively. The established method has been successfully applied to a bioequivalence study of two xanthinol nicotinate tablets for 20 healthy volunteers.

The diversity (richness and community composition) of ammonia-oxidizing archaea (AOA) and bacteria (AOB) in paddy soil with different nitrogen (N) fertilizer amendments for 5 weeks were investigated using quantitative real-time polymerase chain reaction, denaturing gradient gel electrophoresis (DGGE) jand clone library analysis based on the ammonia monooxygenase alpha-subunit (amoA) gene. Ammonia-oxidizing archaea predominated among ammonia-oxidizing prokaryotes in the paddy soil, and the AOA:AOB DNA-targeted amoA gene ratios ranged from 1.2 to 69.3. Ammonia-oxidizing archaea were more abundant in the rhizosphere than in bulk soil. Rice cultivation led to greater abundance of AOA than AOB amoA gene copies and to differences in AOA and AOB community composition. These results show that AOA is dominant in the rhizosphere paddy soil in this study, and we assume that AOA were influenced more by exudation from rice root (e.g. oxygen, carbon dioxide) than AOB.

The abundance and composition of soil ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA) communities under different long-term (17 years) fertilization practices were investigated using real-time polymerase chain reaction and denaturing gradient gel electrophoresis (DGGE). A sandy loam with pH (H(2)O) ranging from 8.3 to 8.7 was sampled in years 2006 and 2007, including seven fertilization treatments of control without fertilizers (CK), those with combinations of fertilizer nitrogen (N), phosphorus (P) and potassium (K): NP, NK, PK and NPK, half chemical fertilizers NPK plus half organic manure (1/2OMN) and organic manure (OM). The highest bacterial amoA gene copy numbers were found in those treatments receiving N fertilizer. The archaeal amoA gene copy numbers ranging from 1.54 x 10(7) to 4.25 x 10(7) per gram of dry soil were significantly higher than those of bacterial amoA genes, ranging from 1.24 x 10(5) to 2.79 x 10(6) per gram of dry soil, which indicated a potential role of AOA in nitrification. Ammonia-oxidizing bacteria abundance had significant correlations with soil pH and potential nitrification rates. Denaturing gradient gel electrophoresis patterns revealed that the fertilization resulted in an obvious change of the AOB community, while no significant change of the AOA community was observed among different treatments. Phylogenetic analysis showed a dominance of Nitrosospira-like sequences, while three bands were affiliated with the Nitrosomonas genus. All AOA sequences fell within cluster S (soil origin) and cluster M (marine and sediment origin). These results suggest that long-term fertilization had a significant impact on AOB abundance and composition, while minimal on AOA in the alkaline soil.

Objective: To investigate the clinical effect of Chinese herbal medicine combined with auto-hemopoietic stem cell transplantation for refractory severe autoimmune disease (RSAID)., Methods: Auto-hemopoietic stem cell transplantation was conducted for the treatment of 7 patients with RSAID, including 4 cases of systemic lupus erythematosus (SLE), 2 myasthenia gravis (MG) and 1 polymyositis (PM) with the FAC program (consisting of fludarabine, antithymocyte globulin, and cyclophosphamide FAC) as for pretreatment. Traditional Chinese medicine (TCM) was given orally after transplantation to patients according to their syndrome type., Results: The hemopoiesis function was smoothly re-established in all patients, with their clinical symptoms and signs obviously improved, laboratory indexes negatively conversed or obviously decreased, and withdrawal or dose reducing of medicines., Conclusion: Combined use of TCM after auto-hemopoietic stem cell transplantation can accelerate patients' hemopoiesis function re-establishment, with significant effects in reducing complications, improving clinical symptoms and signs.

The abundance and composition of soil ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA) were investigated by using quantitative real-time polymerase chain reaction, cloning and sequencing approaches based on amoA genes. The soil, classified as agri-udic ferrosols with pH (H(2)O) ranging from 3.7 to 6.0, was sampled in summer and winter from long-term field experimental plots which had received 16 years continuous fertilization treatments, including fallow (CK0), control without fertilizers (CK) and those with combinations of fertilizer nitrogen (N), phosphorus (P) and potassium (K): N, NP, NK, PK, NPK and NPK plus organic manure (OM). Population sizes of AOB and AOA changed greatly in response to the different fertilization treatments. The NPK + OM treatment had the highest copy numbers of AOB and AOA amoA genes among the treatments that received mineral fertilizers, whereas the lowest copy numbers were recorded in the N treatment. Ammonia-oxidizing archaea were more abundant than AOB in all the corresponding treatments, with AOA to AOB ratios ranging from 1.02 to 12.36. Significant positive correlations were observed among the population sizes of AOB and AOA, soil pH and potential nitrification rates, indicating that both AOB and AOA played an important role in ammonia oxidation in the soil. Phylogenetic analyses of the amoA gene fragments showed that all AOB sequences from different treatments were affiliated with Nitrosospira or Nitrosospira-like species and grouped into cluster 3, and little difference in AOB community composition was recorded among different treatments. All AOA sequences fell within cluster S (soil origin) and cluster M (marine and sediment origin). Cluster M dominated exclusively in the N, NP, NK and PK treatments, indicating a pronounced difference in the community composition of AOA in response to the long-term fertilization treatments. These findings could be fundamental to improve our understanding of the importance of both AOB and AOA in the cycling of nitrogen and other nutrients in terrestrial ecosystems.

The objective of study was to investigate whether U937 cells-loaded dendritic cells (DCs) could induce anti-leukemic immune activity. The apoptosis of U937 cells was induced by artesunate (ART). DCs derived from peripheral blood mononuclear cells of health donors were loaded with apoptotic U937 cells, and induced to maturation in the presence of TNF-alpha. Matured DCs were cocultured with autologous T-lymphocytes, and combined with IL-2 in order to induce the leukemia-specific CTL. The phenotypes of DCs and T lymphocytes were tested by flow cytometry. The ability of DC capturing antigens was measured by Dextran-FITC endocytosis. The IL-12p70 level was assayed by ELISA kit. The proliferation of CTL and CTL activity were measured by MTT assay. The results showed that the apoptotic rate of the U937 cells was 51.2% when U937 cells were induced by 1 microg/ml ART for 48 hours in vitro. DCs had the most powerful ability of endocytosis in its immature phase. Apoptotic U937 cells could not induce the features of DC maturation, and apoptotic U937 cell-pulsed immature DCs could be matured with TNF-alpha. The IL-12p70 level secreded by apoptotic U937 cell-loaded mature DCs (mDC-(Apo)U937) was higher than that of non-loaded mDC. The proliferation of autologous T lymphocytes co-cultured with mDC-(Apo)U937 was significantly remarkable and the content of CD8(+) CTL was significantly higher in comparison with any other groups. CTL induced by mDC-(Apo)U937 had stronger killing effect on U937 cells than NB4 (p < 0.01). It is concluded that the mDC-(Apo)U937 can effectively generate T cell-mediated dendritic antileukemic responses in vitro.

Background: Although roxithromycin and ambroxol HCl were often administered concomitantly for the treatment of respiratory infections, the pharmacokinetic interactions between them have not been reported. We investigated the interactions between these drugs in health male Chinese volunteers by LC-MS/MS in human plasma., Methods: The pharmacokinetics were studied in 12 healthy male Chinese volunteers after an overnight fast by a single oral dose, 4-way crossover design with a period of 7-day washout. Each subjects was randomized to receive a single oral dose of 1 compound roxithromycin (150 mg) and ambroxol HCl (30 mg) dispersible tablet (test formulation, treatment A), one 150 mg roxithromycin dispersible tablet together with one 30 mg ambroxol HCl tablet (combined reference formulations, treatment B), one 150 mg roxithromycin dispersible tablet (reference formulation I, treatment C), or one 30 mg ambroxol HCl tablet (reference formulation II, treatment D) with 250 ml of water. Venous blood was collected at pre-dose (0 h) and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72 h after dosing. The plasma concentrations of roxithromycin and ambroxol HCl were simultaneously determined by using a validated internal standard LC-MS/MS method., Results: No significant differences were observed for the major pharmacokinetic parameters such as C(max), T(max), t(1/2) and AUC of both roxithromycin and ambroxol HCl between different treatments., Conclusion: The pharmacokinetics of both roxithromycin and ambroxol HCl are not affected by their concomitant oral administration. Therefore, there are no obvious pharmacokinetic interactions between roxithromycin and ambroxol HCl after oral administration. Roxithromycin and ambroxol HCl dispersible tablets were bioequivalent with reference to the roxithromycin dispersible tablets and ambroxol HCl tablets in combination usage.

Culturable microorganisms provide very limited information on soil microbial diversity, because only 0.1%-10% of soil microorganisms can be cultured under conventional laboratory conditions. A novel culture-independent approach, i.e., metagenomic methodology, has been developed as an effective tool for the discovery of new natural products and microbial functions. Soil metagenomic methods, comprising isolation of soil DNA and construction and screening of clone libraries, enable to peep at more complete scenario of soil microbial communities, and thus, to better understand their interactions. This methodology is of great potential for use in the studies of soil microbial communities and their functional genes, and in the discovery of new biocatalysts for industry and pharmacy. This review summarized some advances of soil metagenomic study.

Synthetic lethality (SL) and synthetic viability (SV) are commonly studied genetic interactions in the targeted therapy approach in cancer. In SL, inhibiting either of the genes does not affect the cancer cell survival, but inhibiting both leads to a lethal phenotype. In SV, inhibiting the vulnerable gene makes the cancer cell sick; inhibiting the partner gene rescues and promotes cell viability. Many low and high-throughput experimental approaches have been employed to identify SLs and SVs, but they are time-consuming and expensive. The computational tools for SL prediction involve statistical and machine-learning approaches. Almost all machine learning tools are binary classifiers and involve only identifying SL pairs. Most importantly, there are limited properties known that best describe and discriminate SL from SV. We developed MAGICAL (Multi-class Approach for Genetic Interaction in Cancer via Algorithm Learning), a multi-class random forest based machine learning model for genetic interaction prediction. Network properties of protein derived from physical protein-protein interactions are used as features to classify SL and SV. The model results in an accuracy of ~80% for the training dataset (CGIdb, BioGRID, and SynLethDB) and performs well on DepMap and other experimentally derived reported datasets. Amongst all the network properties, the shortest path, average neighbor2, average betweenness, average triangle, and adhesion have significant discriminatory power. MAGICAL is the first multi-class model to identify discriminatory features of synthetic lethal and viable interactions. MAGICAL can predict SL and SV interactions with better accuracy and precision than any existing binary classifier. Author summary: Targeted therapy aims to selectively target cancer cells without damaging the normal ones. Synthetic lethality is a negative genetic interaction in which alteration of both genes leads to cell death and mediates drug sensitivity. In contrast, synthetic viability is a positive genetic interaction in which gene alteration rescues the cell sickness induced by alteration in the vulnerable gene and promotes cell viability, leading to drug resistance. Hence, identifying these genetic interactions is crucial to fostering selective treatment and improving the patient's health. We have designed MAGICAL, a multi-class classifier for predicting genetic interactions, a machine-learning model that can predict SL and SV based on the network properties. We aim to address how these genetic interactions get affected when the placement of the nodes (genes) in the network changes. As genetic interaction in cancer has a key role in precision oncology/targeted therapy, this work would enable researchers to understand how these interactions foster better treatment. [ABSTRACT FROM AUTHOR]

Statistical characterizations of complex network structures can be obtained from both the Ihara Zeta function (in terms of prime cycle frequencies) and the partition function from statistical mechanics. However, these two representations are usually regarded as separate tools for network analysis, without exploiting the potential synergies between them. In this paper, we establish a link between the Ihara Zeta function from algebraic graph theory and the partition function from statistical mechanics, and exploit this relationship to obtain a deeper structural characterisation of network structure. Specifically, the relationship allows us to explore the connection between the microscopic structure and the macroscopic characterisation of a network. We derive thermodynamic quantities describing the network, such as entropy, and show how these are related to the frequencies of prime cycles of various lengths. In particular, the n-th order partial derivative of the Ihara Zeta function can be used to compute the number of prime cycles in a network, which in turn is related to the partition function of Bose–Einstein statistics. The corresponding derived entropy allows us to explore a phase transition in the network structure with critical points at high and low-temperature limits. Numerical experiments and empirical data are presented to evaluate the qualitative and quantitative performance of the resulting structural network characterisations. [ABSTRACT FROM AUTHOR]

This paper deals with the free and forced, linear and nonlinear vibration of functionally graded (along with thickness) nanotube, considering the non-uniform cross-section that made a two-dimensional functionally graded (2D-FG) structure. The bi-dimensional nanostructure-dependent governing equation is modeled based on the classic beam theory (Euler-Bernoulli), and they are derived by Hamilton's principle based on nonlocal gradient strain theory considering the von-Kármán nonlinear strain and the external harmonic load. To solve the general equations and calculate the results, the generalized differential quadrature method (GDQM) was used coupled with the numerical iteration method for the nonlinear response. The results are discussed for the different simply-supported and clamped boundary conditions. The 2D-FG nanotube's behavior is analyzed for different nonlinear amplitudes, nonlocal strain gradient parameters and nonlocal parameters, different rates of cross-sections, and different material distributions. [ABSTRACT FROM AUTHOR]

Irrigated and rain-fed rice fields are unique agroecosystems and anthropogenic wetlands whose main feature is seasonal flooding. Flooded soils are characterized by spatiotemporal shifts and oscillation of the oxygen status and redox potential, sustaining varieties of microbial metabolisms, where bacteria and methanogenic archaea play principal roles and thus have been the major research targets. In this review, we focus on the diversity and ecology of protists—often overlooked biological entities—in wetland rice field soils. Protists with different ecological functions, i.e., phagotrophs, phototrophs, saprotrophs, and parasites, inhabit a rice field soil with a community- and individual-level adaptation to the wide range of oxygen tensions and redox potential. Other agricultural managements like fertilization and char application also influence the protist community. They link to the material cycling in rice soil and affect the activities and community composition of the microorganisms involved in the biogeochemical cycles. Rice roots are the hot spot for protists, which control the rhizospheric bacterial community and could increase the plant productivity through enhancing nutrient release and altering bacterial activities. This review highlights the essential roles of protists in a wetland rice field soil and needs for further research to fill the gaps in knowledge regarding the diversity and functions of the protists in this unique agroecosystem. [ABSTRACT FROM AUTHOR]

The bacterial microbiome plays crucial role in plants' resistance to diseases, nutrient uptake and productivity. We examined the microbiome characteristics of healthy and unhealthy strawberry farms, focusing on soil (bulk soil, rhizosphere soil) and plant (roots and shoots). The relative abundance of most abundant taxa were correlated with the chemical soil properties and shoot niche revealed the least amount of significant correlations between the two. While alpha and beta diversities did not show differences between health groups, we identified a number of core taxa (16–59) and marker bacterial taxa for each healthy (Unclassified Tepidisphaerales, Ohtaekwangia, Hydrocarboniphaga) and dysbiotic (Udaeobacter, Solibacter, Unclassified Chitinophagales, Unclassified Nitrosomonadaceae, Nitrospira, Nocardioides, Tardiphaga, Skermanella, Pseudomonas, Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium, Curtobacterium) niche. We also revealed selective pressure of strawberry rhizosphere soil and roots plants in unhealthy plantations increased stochastic ecological processes of bacterial microbiome assembly in shoots. Our findings contribute to understanding sustainable agriculture and plant-microbiome interactions. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a highly prevalent and lethal cancer worldwide. Approximately 45% of CRC patients harbor a gain-in-function mutation in KRAS. KRAS is the most frequently mutated oncogene accounting for approximately 25% of all human cancers. Gene mutations in KRAS cause constitutive activation of the KRAS protein and MAPK/AKT signaling, resulting in unregulated proliferation and survival of cancer cells and other aspects of malignant transformation, progression, and metastasis. While KRAS has long been considered undruggable, the FDA recently approved two direct acting KRAS inhibitors, Sotorasib and Adagrasib, that covalently bind and inactivate KRASG12C. Both drugs showed efficacy for patients with non-small cell lung cancer (NSCLC) diagnosed with a KRASG12C mutation, but for reasons not well understood, were considerably less efficacious for CRC patients diagnosed with the same mutation. Thus, it is imperative to understand the basis for resistance to KRASG12C inhibitors, which will likely be the same limitations for other mutant specific KRAS inhibitors in development. This review provides an update on clinical trials involving CRC patients treated with KRASG12C inhibitors as a monotherapy or combined with other drugs. Mechanisms that contribute to resistance to KRASG12C inhibitors and the development of novel RAS inhibitors with potential to escape such mechanisms of resistance are also discussed. [ABSTRACT FROM AUTHOR]

Wheat straw returning is a common agronomic measure in the farmland. Understanding organic carbon transformation is of great significance for carbon budget under the premise of widespread distribution of cadmium (Cd) contaminated soils. An incubation experiment was conducted to assess the influence of Cd contamination on the decomposition and accumulation of total organic carbon (TOC) as well as the composition and abundance of bacterial communities in eight soil types with wheat straw addition. The results showed that inhibition of Cd contamination on microbially mediated organic carbon decomposition was affected by soil types. The lower cumulative C mineralization and higher TOC content could be observed in the acidic soils relative to that in the alkaline soils. The content of Cd in soil exhibits different effects on the inhibition in decomposition of TOC. The high dosage level of Cd had stronger inhibitory impact due to its high toxicity. The decomposition of TOC was restricted by a reduction in soil bacterial abundance and weakening of bacterial activities. Redundancy analysis (RDA) indicated that Proteobacteria and Gemmatimonadetes were abundant in alkaline Cd-contaminated soils with wheat straw addition, while Bacteroidetes dominated cumulative C mineralization in acidic Cd-contamination soils. Moreover, the abundance of predicted functional bacteria indicated that high-dose Cd-contamination and acid environment all inhibited the decomposition of TOC. The present study suggested that pH played an important role on carbon dynamics in the Cd-contaminated soils with wheat straw addition. [ABSTRACT FROM AUTHOR]

Forest fire is a major disturbance in mountainous ecosystems across the world. It impacts the composition, functioning, and structure of the forest ecosystem. Demographic pressure and the related climatic factors are thought to exacerbate the danger of forest fires, although there is a lack of statistical data to support this, particularly in South Asian countries with limited historical records. The study looks at how forest fires interact with their causative variables, such as population, topography, vegetation, and climate regimes, in the forests of Northern India. In order to do so, the paper presents a 15-year trend analysis of forest burn scars. This investigation confirmed the utility of principal component analysis using multisource spatial data and correlation matrices. The findings reveal that the occurrence and intensity of forest fires in mountainous locations are influenced by anthropogenic activities, forests near roads and settlements are extremely vulnerable. Based on the analysis, we emphasize the need for restructuring the existing policies like National Action Plan for forest fires and forest fire prevention and management scheme into more practical science-based policies. These findings may be utilized in planning effective fire control processes in time, and the technique provided in this study may be used to discover potential fire-risk zones in other areas. [ABSTRACT FROM AUTHOR]

: CRISPR/Cas12a‐based combinational screening has shown remarkable potential for identifying genetic interactions. Here, we describe an innovative method for combinational genetic screening with rapid construction of a dual‐CRISPR RNA (crRNA) library using gene splicing through overlap extension PCR (SOE PCR) and the adoption of CeCas12a, which we previously identified with strict PAM recognition and low off‐targeting to guarantee fidelity and efficiency. The custom‐pooled SOE crRNA array (SOCA) library for double‐knockout screening could be conveniently constructed in the laboratory for widespread use, and the CeCas12a‐mediated high‐fidelity screen displayed good performance even under a negative selection screen. By designing a SOCA dual‐crRNA library that covered most of the kinase and metabolism‐associated gene targets of FDA‐approved drugs implicated in hepatocellular carcinoma (HCC) tumourigenesis, novel cross‐talk between the two gene sets was negatively selected to inhibit HCC cell growth in vitro and in vivo and was validated using virtual double‐knockdown screening based on TCGA databases. Thus, this rapid, efficient and high‐fidelity double‐knockout screening system is promising for systemically identifying potential genetic interactions between multiple gene sets or combinations of FDA‐ approved drugs for clinical translational medicine in the future. [ABSTRACT FROM AUTHOR]

Increased alcohol intake over decades leads to progressive alcohol-related liver disease (ALD) and contributes to increased mortality. It is characterized by reduced platelet count. Platelets have a role in protecting vascular integrity and involved in liver regeneration. Alcohol affects the platelet count and its function. Platelet function is regulated by their proteins, released during pathophysiological conditions. Therefore, platelet proteome plays a vital role during ALD. This preliminary study consists of 10 patients with ALD. It includes the preparation of human platelets for the proteomic approach. We performed liquid chromatography-mass spectrometry for the samples. A total of 536 proteins were identified in patients with ALD of which 31 proteins were mentioned as a candidate based on their clinical significance. The advancement of diagnostic or therapeutic tools based on the application of platelet proteins in ALD is still far off. Platform for platelet and its proteome research may give diagnostic and prognostic insights into ALD. Platelet proteomes could possibly be concluded as therapeutic and potential diagnostic or prognostic markers in ALD. [ABSTRACT FROM AUTHOR]

Mesoporous silica nanoparticles (MSNPs) are inorganic nanoparticles that have been comprehensively investigated and are intended to deliver therapeutic agents. MSNPs have revolutionized the therapy for various conditions, especially cancer and infectious diseases. In this article, the viability of MSNPs' administration for lung cancer therapy has been reviewed. However, certain challenges lay ahead in the successful translation such as toxicology, immunology, large-scale production, and regulatory matters have made it extremely difficult to translate such discoveries from the bench to the bedside. This review highlights recent developments, characteristics, mechanism of action and customization for targeted delivery. This review also covers the most recent data that sheds light on MSNPs' extraordinary therapeutic potential in fighting lung cancer as well as future hurdles. Article highlights Background Lung cancer (LC) is one of the leading causes of cancer-related mortality worldwide. It has been estimated that 19.5 million novel tumor instances and 6.09 million fatalities happened in 2022. The conventional therapies are not successful in the treatment of LC, because of the resistance of LC cells against the usual chemotherapeutic agents. There is an urgent need for the development of innovative illness treatment techniques. This paper highlights the potential of mesoporous silica nanoparticles (MSNPs) in LC. Molecular mechanism of LC & inhibitory pathways LC is characterized by a neoplastic metamorphosis of epithelial cells of the lungs. LC is not only induced by mutations, but molecular alterations of the anaplastic lymphoma kinase gene are also the prevalent inducer of LC. The article highlights the mechanism and various inhibitory pathways in LC. Diagnosis & treatment methods for LC The article highlights various diagnosis strategies including physical evaluation, analysis of blood and urine samples, x-ray, MRI, computed tomography scan, positron emission tomography (PET) scan, etc. The multifactorial treatments including surgery, chemotherapy, radiotherapy, radiosurgery, and immunotherapy for LC have also been discussed in the article. Two potential targeting strategies, i.e., passive targeting and active targeting are employed as a potential approach to anticancer therapy. Emergence of nanomaterials & role of MSNPs in LC MSNPs have revolutionized the therapy for various conditions, especially cancer and infectious diseases. MSNPs are excellent and unique carriers for drug delivery and cancer therapy owing to their suitable features. The surface functionalization of MSNPs is extremely crucial to increase their effectiveness in vivo while lowering their toxicity. MSNPs are typically employed in pulmonary drug-delivery systems through the process of passive diffusion. Advantages & disadvantages of MSNPs MSNPs possess an ordered structure which is very appropriate for packing high amounts of drug moieties. The toxicology of MSNPs toward specific cell lines may be due to the presence of surface silanolates and/or the formation of silica reactive oxygen species. The structural modifications of MSNPs minimize their toxicities and influence the accumulation and biodegradation rate. Conclusion & Future Perspective MSNPs have demonstrated significant benefits over other nanocarriers in terms of anticancer drug delivery. Employing MSNPs and the EPR effect, neoteric therapeutic strategies can be used to alleviate LC. Prior to clinical trials, it is also essential to standardize any exterior functionalization approaches. [ABSTRACT FROM AUTHOR]

Background: Among the 10% of pancreatic cancers that occur in a familial context, around a third carry a pathogenic variant in a cancer predisposition gene. Genetic studies of pancreatic cancer predisposition are limited by high mortality rates amongst index patients and other affected family members. The genetic risk for pancreatic cancer is often shared with breast cancer susceptibility genes, most notably BRCA2, PALB2, ATM and BRCA1. Therefore, we hypothesized that additional shared genetic etiologies might be uncovered by studying families presenting with both breast and pancreatic cancer. Methods: Focusing on a multigene panel of 276 DNA Damage Repair (DDR) genes, we performed next-generation sequencing in a cohort of 41 families with at least three breast cancer cases and one pancreatic cancer. When the index patient with pancreatic cancer was deceased, close relatives (first or second-degree) affected with breast cancer were tested (39 families). Results: We identified 27 variants of uncertain significance in DDR genes. A splice site variant (c.1605 + 2T > A) in the RAD17 gene stood out, as a likely loss of function variant. RAD17 is a checkpoint protein that recruits the MRN (MRE11-RAD50-NBS1) complex to initiate DNA signaling, leading to DNA double-strand break repair. Conclusion: Within families with breast and pancreatic cancer, we identified RAD17 as a novel candidate predisposition gene. Further genetic studies are warranted to better understand the potential pathogenic effect of RAD17 variants and in other DDR genes. [ABSTRACT FROM AUTHOR]