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There is no definitive approach for assessing mesenteric ischemia and determining the optimal timing for endovascular intervention in the management of spontaneous isolated dissection of the superior mesenteric artery (SISMAD). A 56-year-old male with acute abdominal pain was diagnosed with SISMAD. After evaluating mesenteric ischemia through mesenteric fractional flow reserve (FFR), FFR was 0.72, and the patient was recommended conservative treatment for SISMAD, which involves fasting, total parenteral nutrition, and anticoagulation. The patient's syndrome was relieved after conservative treatment for 14 days without stent implantation. Over the next 5 years, no recurrence of abdominal pain or worsening of SISMAD was observed in the patient. Assessing the severity of mesenteric ischemia can be done through mesenteric FFR. Upon confirmation of the exclusion of risks related to dilatation or rupture of SISMAD aneurysm, an approach in favor of conservative management for SISMAD may indeed be considered pragmatic when the FFR exceeds 0.72. [ABSTRACT FROM AUTHOR]

An order of addition experiment is an experiment to study how the order of addition of components affect the results, with the objective of predicting and determining the optimal order of addition of components. Order of addition experiment are also commonly used in the drug combination therapy, where experimenting with all drugs combinations is unaffordable. To solve this problem, we constructed a new design table, two-level component factorial design table (TLCF), which combine the component orthogonal array design table and the two-level partial factorial design table by matrix product. TLCF can explore the order and dosage effect of components on the results and can greatly reduce the number of experiments. We also prove that the relative D-efficiency of the TLCF can reach 100% and solve an explicit expression for the D-efficiency of the full design. In the simulation experiment, we compare the D-efficiency of the TLCF with the random design table to prove the superiority of TLCF. Finally, we give a treatment plan for the combination of three drugs for glioblastoma based on the TLCF, which provides a new perspective for the precision treatment of patients. [ABSTRACT FROM AUTHOR]

The increased volume of rumors and attention on related topics during the COVID-19 pandemic have had a significant negative social impact. To combat rumors, it is crucial to study the actors involved in their spread. In this study, we first introduce prospect theory and construct an evolutionary game model between network operators and government regulators. We investigate collusion between network operators and Internet rumormongers as well as the regulatory behavior of government agencies. Second, we use prospect value to replace traditional expected utility to construct a profit prospect matrix and apply the dynamic replicator equation to analyze the equilibrium stability of the model. The stability conditions of the game between the two parties are closely related to the government's regulatory costs, and the strength of government punishment after collusion is detected. Finally, we propose relevant countermeasures against collusion problems during the network rumor control period. [ABSTRACT FROM AUTHOR]

Let D be a non-trivial G-block-transitive 3-(v, k, 1) design, where T ≤ G ≤ Aut (T) for some finite non-abelian simple group T. It is proved that if T is a simple exceptional group of Lie type, then T is either the Suzuki group 2 B 2 (q) or G 2 (q) . Furthermore, if T = 2 B 2 (q) then the design D has parameters v = q 2 + 1 and k = q + 1 , and so D is an inverse plane of order q, and if T = G 2 (q) then the point stabilizer in T is either SL 3 (q). 2 or SU 3 (q). 2 , and the parameter k satisfies very restricted conditions. [ABSTRACT FROM AUTHOR]

Background: The metastasis accounts for most deaths from breast cancer (BRCA). Understanding the molecular mechanisms of BRCA metastasis is urgently demanded. Flap Endonuclease 1 (FEN1), a pivotal factor in DNA metabolic pathways, contributes to tumor growth and drug resistance, however, little is known about the role of FEN1 in BRCA metastasis. Methods and results: In this study, FEN1 expression and its clinical correlation in BRCA were investigated using bioinformatics, showing being upregulated in BRCA samples and significant relationships with tumor stage, node metastasis, and prognosis. Immunohistochemistry (IHC) staining of local BRCA cohort indicated that the ratio of high FEN1 expression in metastatic BRCA tissues rose over that in non-metastatic tissues. The assays of loss-of-function and gain-of-function showed that FEN1 enhanced BRCA cell proliferation, migration, invasion, xenograft growth as well as lung metastasis. It was further found that FEN1 promoted the aggressive behaviors of BRCA cells via Signal Transducer and Activator of Transcription 3 (STAT3) activation. Specifically, the STAT3 inhibitor Stattic thwarted the FEN1-induced enhancement of migration and invasion, while the activator IL-6 rescued the decreased migration and invasion caused by FEN1 knockdown. Additionally, overexpression of FEN1 rescued the inhibitory effect of nuclear factor-κB (NF-κB) inhibitor BAY117082 on phosphorylated STAT3. Simultaneously, the knockdown of FEN1 attenuated the phosphorylation of STAT3 promoted by the NF-κB activator tumor necrosis factor α (TNF-α). Conclusions: These results indicate a novel mechanism that NF-κB-driven FEN1 contributes to promoting BRCA growth and metastasis by STAT3 activation. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to translate and culturally adapt the standardized outcomes in nephrology–hemodialysis fatigue (SONG–HD fatigue) scale and to assess the psychometric properties of the Chinese version of the SONG–HD fatigue (C-SONG–HD fatigue) scale. Methods: Forward and back translations were used to translate the SONG–HD fatigue scale into Chinese. We used the C-SONG–HD fatigue scale to survey Chinese patients undergoing hemodialysis (HD) in China. We examined the distribution of responses and floor and ceiling effects. Cronbach's alpha and McDonald's omega coefficient, intraclass coefficients, and Spearman correlations were used to assess internal consistency reliability, test–retest reliability, and convergent validity, respectively. Responsiveness was also evaluated. Results: In total, 489 participants across southeast China, northwest China, and central China completed the study. The C-SONG–HD fatigue scale had good internal consistency (Cronbach's alpha coefficient 0.861, omega coefficient 0.916), test–retest reliability (intraclass correlation coefficient 0.695), and convergent validity (Spearman correlation 0.691). The analysis of all first-time HD patients did not show notable responsiveness, and only patients with temporary vascular access had good responsiveness with an effect size (ES) of 0.54, a standardized response mean (SRM) of 0.85, and a standard error of measurement (SEM) of 0.77. Conclusion: The Chinese version of the SONG–HD fatigue scale showed satisfactory reliability and validity in patients undergoing hemodialysis (HD) in China. It could be used as a tool to measure the fatigue of Chinese HD patients. [ABSTRACT FROM AUTHOR]

Background: Cyclic guanosine monophosphate (cGMP)-dependent protein kinase I (PKG-I), a serine/threonine kinase, is important in tumor development. The present study determines that the cGMP/PKG I pathway is essential for promoting cell proliferation and survival in human ovarian cancer cells, whereas cGMP analog has been shown to lead to growth inhibition and apoptosis of various cancer cells. The role of cGMP/PKG I pathway in epithelial ovarian cancer (EOC), therefore, remains controversial. We investigated the effect of cGMP/PKG I pathway and the underlying mechanism in EOC. Methods and results: The results showed that exogenous 8-Bromoguanosine-3′, 5′-cyclic monophosphate (8-Br-cGMP) (cGMP analog) could antagonize the effects by EGF, including suppressing proliferation, invasion and migration of EOC cells. In vivo, 8-Br-cGMP hampered the growth of the xenograft tumor. Additionally, the expressions of epidermal growth factor receptor (EGFR), matrix metallopeptidase 9 (MMP9), proliferating cell nuclear antigen and Ki67 in xenograft tumor were decreased after 8-Br-cGMP intervention. Further research demonstrated that 8-Br-cGMP decreased the phosphorylation of EGFR (Y992) and downstream proteins phospholipase Cγ1 (PLC γ1) (Y783), calmodulin kinase II (T286) and inhibited cytoplasmic Ca2+ release as well as PKC transferring to cell membrane. It's worth noting that the inhibition was 8-Br-cGMP dose-dependent and 8-Br-cGMP showed similar inhibitory effect on EOC cells compared with U-73122, a specific inhibitor of PLC γ1. Conclusions: The activation of endogenous PKG I by addition of exogenous 8-Br-cGMP could inhibit EOC development probably via EGFR/PLCγ1 signaling pathway. 8-Br-cGMP/PKG I provide a new insight and strategy for EOC treatment. [ABSTRACT FROM AUTHOR]

Nitrification inhibitors (NIs) are considered as an effective strategy for reducing nitrification rate and related environmental nitrogen (N) loss. However, whether plant-derived biological NIs had an advantage over chemical NIs in simultaneously inhibiting nitrification rate and N2O production remains unclear. Here, we conducted an aerobic 15N microcosmic incubation experiment to compare the effects of a biological NI (methyl 3-(4-hydroxyphenyl) propionate, MHPP) with three chemical NIs, 2-chloro-6-(trichloromethyl) pyridine (nitrapyrin), dicyandiamide (DCD), and 3,4-dimethylpyrazole phosphate (DMPP) on (i) gross N mineralization and nitrification rate and (ii) the relative importance of nitrification and denitrification in N2O emission in a calcareous soil. The results showed that DMPP significantly inhibited m_gross rate (P < 0.05), whereas DCD, nitrapyrin, and MHPP only numerically inhibited it. Gross N nitrification (n_gross) rates were inhibited by 9.48% in the DCD treatment to 51.5% in the nitrapyrin treatment. Chemical NIs primarily affected the amoA gene abundance of ammonia-oxidizing bacteria (AOB), whereas biological NIs affected the amoA gene abundance of ammonia-oxidizing archaea (AOA) and AOB. AOB's community composition was more susceptible to NIs than AOA, and NIs mainly targeted Nitrosospira clusters of AOB. Chemical NIs of DCD, DMPP, and nitrapyrin proportionally reduced N2O production from nitrification and denitrification. However, the biological NI MHPP stimulated short-term N2O emission and increased the proportion of N2O from denitrification. Our findings showed that the influence of NIs on gross N mineralization rate (m_gross) was dependent on the NI type. MHPP exhibited a moderate n_gross inhibitory capacity compared with the three chemical NIs. The mechanisms of chemical and biological NIs inhibiting n_gross can be partly attributed to changes in the abundance and community of ammonia oxidizers. A more comprehensive evaluation is needed to determine whether biological NIs have advantages over chemical NIs in inhibiting greenhouse gas emissions. [ABSTRACT FROM AUTHOR]

Purpose: This study intended to compare the difference between the anterior talofibular ligament (ATFL) and posterior talofibular ligament (PTFL) angle with chronic ankle instability (CAI) patients and healthy volunteers, and to confirm whether using the ATFL–PTFL angle could be a reliable assessment method for CAI, so as to improve the accuracy and specificity of clinical diagnosis. Methods: This retrospective study included 240 participants: 120 CAI patients and 120 healthy volunteers between 2015 and 2021. The ATFL–PTFL angle of the ankle region was gaged in the cross-sectional supine position on MRI between two groups. After participants undergoing a comprehensive MRI scanning, ATFL–PTFL angles were regarded as the main indicator of patients with the injured ATFLs and healthy volunteers to compare, and were measured by an experienced musculoskeletal radiologist. Moreover, other qualitative and quantitative indicators referring to anatomical and morphological characteristics of the AFTL were included in this study with MRI, such as the length, width, thickness, shape, continuity, and signal intensity of the ATFL, which can be used as secondary indicators. Results: In the CAI group, the ATFL–PTFL angle was 90.8° ± 5.7°, which was significantly different from the non-CAI group where the ATFL–PTFL angle for 80.0° ± 3.7° (p < 0.001). As for the ATFL-MRI characteristics, the length (p = 0.003), width (p < 0.001), and thickness (p < 0.001) in the CAI group were also significantly different from the non-CAI group. Over 90% of the cases, patients of the CAI group had injured ATFL with an irregular shape, non-continuous, and high or mixed signal intensity. Conclusion: Compared with healthy people, the ATFL–PTFL angle of most CAI patients is larger, which can be used as a secondary index to diagnose CAI. However, the MRI characteristic changes of ATFL may not relate to the increased ATFL–PTFL angle. [ABSTRACT FROM AUTHOR]

Objective: Chronic hepatitis B (CHB) and metabolic dysfunction-associated fatty liver disease (MAFLD) are the leading causes of hepatocellular carcinoma (HCC). We aim to explore the impact of concurrent MAFLD on the risk of HCC in CHB. Methods: Patients with CHB were consecutively recruited from 2006 to 2021. MAFLD was defined by steatosis and either obesity, diabetes mellitus, or other metabolic abnormalities. The cumulative incidence of HCC and associated factors were compared between the MAFLD and non-MAFLD groups. Results: 10,546 treatment-naïve CHB patients were included with a median follow-up of 5.1 years. CHB patients with MAFLD (n = 2212) had fewer hepatitis B e antigen (HBeAg)-positivity, lower HBV DNA levels, and Fibrosis-4 index compared with the non-MAFLD group (n = 8334). MAFLD was independently associated with a 58% reduced risk of HCC (adjusted hazard ratio [aHR] 0.42, 95% confidence interval [CI] 0.25–0.68, p < 0.001). Furthermore, steatosis and metabolic dysfunction had distinct effects on HCC. Steatosis was protective against HCC (aHR 0.45, 95% CI 0.30–0.67, p < 0.001), while a greater burden of metabolic dysfunction increased the risk (aHR 1.40 per dysfunction increase, 95% CI 1.19–1.66, p < 0.001). The protective effect of MAFLD was further confirmed in analysis with inverse probability of treatment weighting (IPTW), patients who had undergone antiviral therapy, those with probable MAFLD, and after multiple imputation for missing data. Conclusions: Concurrent hepatic steatosis is independently associated with a lower risk of HCC, whereas the increasing burden of metabolic dysfunction aggravates the risk of HCC in untreated CHB patients. [ABSTRACT FROM AUTHOR]

Let D be a nontrivial 3-(v, k, 1) design admitting a block-transitive group G of automorphisms. A recent work of Gan and the second author asserts that G is either affine or almost simple. In this paper, it is proved that if G is almost simple with socle an alternating group, then D is the unique 3-(10, 4, 1) design, and G = PGL (2 , 9) , M 10 or Aut (A 6) = S 6 : Z 2 , and G is flag-transitive. [ABSTRACT FROM AUTHOR]

Ferroptosis, a newly identified form of cell death, is characterized by iron overload and accumulation of lipid reactive oxygen species. Inactivation of pathways, such as glutathione/glutathione peroxidase 4, NAD(P)H/ferroptosis suppressor protein 1/ubiquinone, dihydroorotate dehydrogenase/ubiquinol, or guanosine triphosphate cyclohydrolase-1/6(R)-l-erythro-5,6,7,8-tetrahydrobiopterin pathways, have been found to induce ferroptosis. The accumulating data suggest that epigenetic regulation can determine cell sensitivity to ferroptosis at both the transcriptional and translational levels. While many of the effectors that regulate ferroptosis have been mapped, epigenetic regulation in ferroptosis is not yet fully understood. Neuronal ferroptosis is a driver in several central nervous system (CNS) diseases, such as stroke, Parkinson's disease, traumatic brain injury, and spinal cord injury, and thus, research on how to inhibit neuronal ferroptosis is required to develop novel therapies for these diseases. In this review, we have summarized epigenetic regulation of ferroptosis in these CNS diseases, focusing in particular on DNA methylation, non-coding RNA regulation, and histone modification. Understanding epigenetic regulation in ferroptosis will hasten the development of promising therapeutic strategies in CNS diseases associated with ferroptosis. [ABSTRACT FROM AUTHOR]

Tungsten-tin-(rare-metal) deposits are most commonly granite-related and an important source of critical metals. This study describes the fluid evolution in the Tiantangshan Rb-Sn-W deposit, Nanling Range, China, and discusses the implications for mineralizing processes. Mineralization at Tiantangshan is spatially zoned. The greisen roof hosts wolframite-cassiterite quartz veins. The surrounding volcanic rocks host biotite quartz veins (Rb mineralization) crosscut by cassiterite quartz veins and sphalerite-galena quartz veins. The earliest intermediate-density fluids are responsible for the early W-(Sn)-Rb mineralization and evolve towards decreasing homogenization temperature (Th) and ratios of W, Sn, Rb, Cs, Fe, and Mn to Na + K as the fluid migrated from the greisen to the volcanic rocks hosted veins (Th: 420 to 350 °C; salinity: 13 to 4 wt% NaCleq). The spatial distribution of mineralization and fluid paragenesis indicates that precipitation of wolframite, early cassiterite, and Rb-rich biotite was associated with a pH increase during fluid-rock interaction. Late cassiterite and intergrown quartz precipitated from a degassing fluid with lower Th (mainly 360 to 340 °C) and salinity (10 to 2 wt% NaCleq) and with distinctly lower Sn concentrations. Late cassiterite precipitation is therefore likely related with depressurization by brittle failure of the rock leading to simultaneous boiling and meteoric water input. Late Pb–Zn mineralization precipitated from low Th (< 320 °C) and salinity (0 to 2 wt% NaCleq) fluids through extensive mixing with meteoric water. The tempo-spatial development of Rb-Sn-W-Pb–Zn mineralization at Tiantangshan was controlled by a mixing fluid regime, where input of meteoric water gradually increased with time. [ABSTRACT FROM AUTHOR]

Purpose: Application of exogenous carbon (C) and nitrification inhibitors are common measures to regulate soil nitrogen cycling and mitigate greenhouse gas emissions. However, we lack knowledge on their direct effects on denitrification processes. Methods: A 15 N anaerobic microcosm experiment was conducted to investigate the effects of exogenous C and/or nitrification inhibitors on denitrification rate, N2O/(N2O + N2) product stoichiometry ratio, and nirS- and nirK-type denitrifiers in a calcareous soil. Exogenous C were wheat straw and wheat straw–derived biochar, and nitrification inhibitors were chemical nitrification inhibitor 3,4-dimethylpyrazole phosphate (DMPP) and biological nitrification inhibitor methyl 3-(4-hydroxyphenyl) propionate (MHPP). Results: Wheat straw, composite with much of liable C, significantly increased denitrification rate (3.96–4.19 times higher than control), N2O emission, and N2O/(N2O + N2) ratio (p < 0.05) by upregulating nirK and nirS genes of denitrifiers, and changing the community structure of nirS-type denitrifiers. By contrast, biochar, composite with much of recalcitrant organic C, increased the N2O/(N2O + N2) ratio but did not stimulate the denitrification rate (P > 0.05). One percent (w/w applied-N) DMPP, 1% MHPP, and 5% MHPP exhibited minor effects on denitrification rate, while 10% MHPP increased the denitrification rate by 1.32 times relative to control (p < 0.05). Wheat straw biochar applied with two nitrification inhibitors reshaped the community structure of nirK- and nirS-type denitrifiers, decreasing the denitrification rate compared with control, and the N2O/(N2O + N2) ratio compared with application of biochar alone (p < 0.05). Conclusions: The direct effects of exogenous C on denitrification and denitrification processes were dependent on the type of exogenous C applied. High dosage of MHPP (> 10% w/w) increased both denitrification rate and N2O/(N2O + N2) ratio. [ABSTRACT FROM AUTHOR]

Magnetic compression technique (MCT) is a popular new anastomosis method. In this paper, we aimed to explore the feasibility of use of MCT for performing cystotomy in rabbits. The parent magnets and daughter magnets for rabbit cystostomy were designed and manufactured according to the anatomical characteristics of rabbit lower urinary tract. Twelve female New Zealand rabbits were used as animal models. After anesthesia, a daughter magnet was inserted into the bladder through the urethra, and the parent magnet was placed on the body surface projection of the bladder over the abdominal wall. The two magnets automatically attract each other. Postoperatively, the state of magnets was monitored daily, and the time when the magnets fell off was recorded. Cystostomy with MCT was successfully performed in all twelve rabbits. The mean operation time was 4.46 ± 0.75 min. The magnets fell off from the abdominal wall after a mean duration of 10.08 ± 1.62 days, resulting in the formation of bladder fistula. Macroscopic and microscopic examination showed that the fistula was well formed and unobstructed. The junction between bladder and abdominal wall was tight and smooth. We provide preliminary experimental evidence of the safety and feasibility of cystostomy based on MCT. [ABSTRACT FROM AUTHOR]

An aerobic 15N microcosmic experiment was conducted to compare the inhibitory effects of the biological nitrification inhibitor (BNI), methyl 3-(4-hydroxyphenyl) propionate (MHPP) at rates of 500 and 1000 mg kg−1 with the synthetic nitrification inhibitor 3,4-dimethylpyrazole phosphate (DMPP) at 1% of applied NH4+, on the gross nitrification rate (n_gross) and on the abundance and community composition of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) of two contrasting soils (pH: 5.10 vs. 8.15, clay content 17.8 vs. 30.8). DMPP inhibited 56.6% of n_gross in the acidic soil and 50.3% in the calcareous soil, whereas MHPP inhibited 18.3–55.5% of n_gross in the acidic soil and 14.1–20.2% in the calcareous soil. MHPP used at the high rate showed the same inhibition on n_gross as DMPP in the acidic soil but not in the calcareous soil. DMPP and MHPP likely regulated n_gross by causing niche differentiation between AOA and AOB. Moreover, the community composition of AOB was more sensitive to nitrification inhibitor application than that of AOA, particularly in the acidic soil. However, the response of AOB community composition was less sensitive to the application of MHPP than to that of DMPP. MHPP mainly targeted Nitrosospira clusters 3a.2, 3b.2, and 9 of the AOB in the acidic soil. [ABSTRACT FROM AUTHOR]

Epigenetics, including histone modifications, play a significant role in central nervous system diseases, but the underlying mechanism remains to be elucidated. The aim of this study was to evaluate the role of H3K27me3 in regulating transcriptomic and pathogenic mechanisms following global ischemic stroke. Here, we found that in vivo ischemic/reperfusion (I/R) injury induced marked upregulation of H3K27me3 in the hippocampus. The administration of GSK-126 to rat brains decreased the levels of H3K27me3 in the hippocampus and reduced neuronal apoptosis after experimental stroke. Furthermore, ChIP-seq data demonstrated that the primary role of GSK-126 in the ischemic brain is to reduce H3K27me3 enrichment, mediating negative regulation of the execution phase of apoptosis and the MAPK signaling pathway. Further study suggested that the protective role of GSK-126 in ischemic rats was antagonized by U0126, an inhibitor of ERK1/2. Collectively, we demonstrated the potential of H3K27me3 as a novel stroke therapeutic target, and GSK-126 exerted a neuroprotective function in ischemic brain injury, which might be associated with activation of the MAPK/ERK pathway. [ABSTRACT FROM AUTHOR]

The results above showed that TaC9-ABE also gave rise to high editing efficiency and a controllable editing window in embryo level and could be an effective tool for generation of animals with point mutations at specific sites. We designed a novel base-editing system for efficient base editing on-target sites free of Cas9-dependent DNA off-targeting in human cells. 1 a The main components of TaC9-ABE and ABE7.10 vectors. b Schematic diagram of the base-editing principle of TaC9-ABE at the target and off-target sites. TaC9-ABE with 6 bp spacer showed high editing efficiency at A5 and A6 sites, and the effective editing window (>20%) was narrowed from A5 to A7 (~3 nt). [Extracted from the article]

MicroRNAs (miRNAs) play crucial roles in gene expression regulation through RNA cleavage or translation repression. Here, we report the identification of an evolutionarily conserved WD40 domain protein as a player in miRNA biogenesis in Arabidopsis thaliana. A mutation in the REDUCTION IN BLEACHED VEIN AREA (RBV) gene encoding a WD40 domain protein led to the suppression of leaf bleaching caused by an artificial miRNA; the mutation also led to a global reduction in the accumulation of endogenous miRNAs. The nuclear protein RBV promotes the transcription of MIR genes into pri-miRNAs by enhancing the occupancy of RNA polymerase II (Pol II) at MIR gene promoters. RBV also promotes the loading of miRNAs into AGO1. In addition, RNA-seq revealed a global splicing defect in the mutant. Thus, this evolutionarily conserved, nuclear WD40 domain protein acts in miRNA biogenesis and RNA splicing. MicroRNAs regulate gene expression through RNA cleavage or translation repression. Here the authors show that RBV, an evolutionarily conserved WD40 domain protein, acts to promote MIR transcription, pri-miRNA processing and miRNA loading into AGO1. [ABSTRACT FROM AUTHOR]

Reconstruction of a century-long historical population distribution on the regional scale is essential to understanding human–environment interactions and socio-environmental problems. This study uses a random forest regression method based on county-level census data, natural suitability, and socio-economic factors to reconstruct the spatiotemporal population distribution of the Tuojiang River Basin from 1911 to 2010 at a 1-km resolution. By comparing the reconstruction results with the actual 2010 population density at the township level, we found that the population spatialization results are congruent with the actual population density distribution, with a determination coefficient (R2) of 0.84. Compared with three widely used gridded population products, the WorldPop population dataset, the gridded population of the world (GPW), and the grid population dataset of china (CHP), our population map showed the highest accuracy. High population density areas, primarily distributed in the districts and counties in well-developed areas, were mainly centered around the Chengdu Plain and its lower reaches where the landscape meets the Yangtze River. Such areas are characterized by moderate elevations and ideal topographical and climatic conditions. In contrast, the high-altitude areas of the southern and southwestern of the Tuojiang River Basin have relatively low population density. Our reconstructive analysis has the potential to benefit regional socio-economic development and planning. [ABSTRACT FROM AUTHOR]

There are no optimal regimens for advanced thymic epithelial tumors (TETs) when frontline chemotherapy fails. In this study, we aimed to assess the activity of Bevacizumab in combination with a routine chemotherapeutic regimen. Patients with advanced TETs who had failed after previous chemotherapy were enrolled in this study. Paclitaxel (160 mg/m2) and cisplatin (70 mg/m2) or carboplatin (area under the curve, 6) plus Bevacizumab (7.5 mg/kg) were intravenously injected on day 1.The treatment was repeated every 3 weeks until the disease progressed or intolerable toxicities occurred. Between March 2018 and August 2020, a total of 49 patients (21 thymoma and 28 thymic carcinoma) received the new treatment. There were 28 men and 21 women with a median age of 50 years (range: 21-73 years). The median number of cycles was 3 (range: 1-6) per patient. The objective response rate (ORR) for all patients was 43% (21/49). The ORRs for thymoma and thymic carcinoma were 24% and 57%, respectively. The median progression-free survival for thymoma and thymic carcinoma was 6 and 8 months, respectively. Hematological toxicities were the main side effects. Paclitaxel and platinum plus Bevacizumab showed promising effects in refractory or relapsed advanced TETs without severe toxicity. Even when applied as salvage therapy, this regimen resulted in a better ORR than frontline chemotherapy. [ABSTRACT FROM AUTHOR]

Neuropathic pain is one of the most common conditions requiring treatment worldwide. Salidroside (SAL), a phenylpropanoid glucoside extracted from Rhodiola, has been suggested to produce an analgesic effect in chronic pain. However, whether SAL could alleviate pain hypersensitivity after peripheral nerve injury and its mode of action remains unclear. Several studies suggest that activation of the spinal NOD-like receptor protein 3 (NLRP3) inflammasome and its related proteins contribute to neuropathic pain's pathogenesis. This study investigates the time course of activation of spinal NLRP3 inflammasome axis in the development of neuropathic pain and also whether SAL could be an effective treatment for this type of pain by modulating NLRP3 inflammasome. In the chronic constriction injury (CCI) mice model, spinal NLRP3 inflammasome-related proteins and TXNIP, the mediator of NLRP3, were upregulated from the 14th to the 28th day after injury. The TXNIP and NLRP3 inflammasome-related proteins were mainly present in neurons and microglial cells in the spinal dorsal horn after CCI. Intraperitoneal injection of SAL at 200 mg/kg for 14 consecutive days starting from the 7th day of CCI injury could ameliorate mechanical and thermal hypersensitivity in the CCI model. Moreover, SAL inhibited the activation of the TXNIP/NLRP3 inflammasome axis and mitigated the neuronal loss of spinal dorsal horn induced by nerve injury. These results indicate that SAL could produce analgesic and neuroprotective effects in the CCI model of neuropathic pain. [ABSTRACT FROM AUTHOR]

DNA methylation and demethylation play an important role in neuropathic pain. In general, DNA methylation of CpG sites in the promoter region impedes gene expression, whereas DNA demethylation contributes to gene expression. Here, we evaluated the methylation status of CpG sites in genomic DNA promoter regions in dorsal root ganglions (DRGs) of diabetic neuropathic pain (DNP) mice. In our research, streptozotocin (STZ) was intraperitoneally injected into mice to construct DNP models. The DNP mice showed higher fasting blood glucose (above 11.1 mmol/L), lower body weight, and mechanical allodynia than control mice. Whole-genome bisulfite sequencing (WGBS) revealed an altered methylation pattern in CpG sites in the DNA promoter regions in DRGs of DNP mice. The results showed 376 promoter regions with hypermethylated CpG sites and 336 promoter regions with hypomethylated CpG sites. In addition, our data indicated that altered DNA methylation occurs primarily on CpG sites in DNA promoter regions. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that differentially methylated CpG sites annotated genes were involved in activities of the nervous and sensory systems. Enrichment analysis indicated that genes in these pathways contributed to diabetes or pain. In conclusion, our study enriched the role of DNA methylation in DNP. [ABSTRACT FROM AUTHOR]

The incidence of pediatric liposarcoma is rare and most published cases lack systematic genetic analyses. We present clinicopathologic and genetic features of 23 liposarcomas aged <22 years. The study cohort comprised 10 males and 13 females (M:F=1:1.3) aged 11–21 years (median 17 years). The tumors predominantly occurred at the extremities (16/23; 69.6%), followed by the head/neck (2/23; 8.7%), chest (2/23; 8.7%), waist (2/23, 8.7%), and retroperitoneum (1/23; 4.3%). The tumor subtypes were sixteen myxoid liposarcoma (ML), one well-differentiated liposarcoma (WDL), two dedifferentiated liposarcoma (DDL), one pleomorphic liposarcoma (PL), and three myxoid pleomorphic liposarcoma (MPL) cases. Fluorescence in situ hybridization analysis identified MDM2/CDK4 amplification in all WDL/DDL cases (3/3; 100%) and DDIT3 rearrangement in all ML cases (13/13; 100%). Whole-exome sequencing indicated that one PL case and one MPL case exhibited RB1 loss. The two tested MPL cases had TP53 mutation and one of them harbored a TP53 germline mutation. Follow-up information was available for 20 patients (20/23; 87.0%) with a median follow-up duration of 42.5 months (range, 13–120 months). Three patients exhibited tumor progression (3/20;15.0%). Seventeen patients (17/20; 85.0%) survived with no evidence of disease. One MPL case (1/20; 5.0%) died of the disease. In conclusion, despite some overlaps, the occurrence, distribution of subtype, and prognosis of liposarcoma are overall different in children and adults. Most MLs and ALT/WDL/DDLs showed similar genetic aberrations with adult counterparts. Molecular features of MPL overlapped with those of conventional PL. The genetic characteristics including Tp53 status of MPL need further investigation. [ABSTRACT FROM AUTHOR]

Controlled release fertilizer (CRF) has been shown to increase crop yield and N use efficiency (NUE) compared with traditional chemical fertilizer (TF). However, few studies examined the effects of CRF on CH4, N2O, and NO emissions simultaneously in alkaline paddy fields under rice–wheat rotation. In the present study, we conducted a 2-year field experiment to compare the effects of different CRF application strategies on these gas emissions with those of TF and explored the effects of CRF on global warming potential (GWP), crop yields, and greenhouse gas emission intensity (GHGI). Results showed that CRF can reduce 0.98–14.3%, 13.3–21.1%, and 8.22–16.3% of CH4, N2O, and NO emissions, respectively, in the studied alkaline paddy field. CRF reduce CH4 emission probably by regulating soil NH4+ concentration. CRF reduce N2O and NO emissions probably by regulating inorganic N content in the studied alkaline paddy soil. CRF had the same effect on annual crop yield as TF, especially when CRF was applied twice in each season and had the same N application rate as TF. Annual crop yields and the agronomic efficiency of N (AEN) increased by 8.24% and 21.6%, respectively. On the average of the two rice–wheat rotation cycles, GHGI significantly decreased by up to 14.1% after the application of CRF as relative to that after the application of TF (P < 0.05). These results suggest that CRF is an environment-friendly N fertilization strategy for mitigating GWP and ensuring high crop yield in an alkaline paddy field under rice–wheat rotation. [ABSTRACT FROM AUTHOR]

GSK-126 is recognized as an inhibitor of enhancer of zeste homolog-2 (EZH2) activity. Because of its inhibition of EZH2 activation, GSK-126 is considered a potential anti-tumor drug. EZH2 is a histone methyltransferase that catalyzes histone 3 tri-methylation at lysine 27 (H3K27me3), resulting in gene silencing. A previous report showed that decreased H3K27me3 levels in the hippocampus may promote seizure susceptibility, possibly restricting the clinical application of GSK-126. The role of GSK-126 in seizure susceptibility was investigated in this study. We first determined a critical concentration of pentamethazol (PTZ) under which mice exhibit no seizures. We then found that mice pretreated with GSK-126 and injected with the same concentration of PTZ experienced marked convulsions. Peripheral injections of GSK-126 decreased H3K27me3 levels in the hippocampus of mice, while some seizure-related genes (Oasl1, Sox7, armcx5, Ncx3, etc.) were found to be differentially expressed in the hippocampus of those mice. These differences in the expression levels might reflect the crucial role of these genes and related pathways in the promotion of seizure susceptibility. Our results suggest that GSK-126 promotes seizure susceptibility due to its role as an EZH2 inhibitor. These findings may provide evidence to support the development of GSK-126 as a clinical drug. [ABSTRACT FROM AUTHOR]

Summary: A new drug, Caba-780, was synthesized by chemical coupling of the heptamethyl phthalocyanine near-infrared fluorescent (NIRF) dye IR-780 and the paclitaxel-based chemotherapeutic drug cabazitaxel. Then, the potential value of Caba-780 in the diagnosis and treatment of castration-resistant prostate cancer (CRPC) was evaluated. The CRPC cell lines DU145 and PC-3, as well as the normal human prostate stromal cell line WPMY-1, were used to evaluate the uptake of Caba-780 and its antitumor effect in vitro. The distribution, antitumor effect, and safety of Caba-780 were also evaluated in tumor-bearing mouse xenograft models. Our results showed that Caba-780 was efficiently absorbed by DU145 and PC-3 cells and that the cytotoxicity of Caba-780 was significantly stronger than that of IR-780 and cabazitaxel. In addition, Caba-780 inhibited the migration and invasion of DU145 and PC-3 cells and promoted apoptosis by prolonging the G2 phase of the cell cycle. Further analysis indicated that Caba-780 could be used to effectively image tumor xenografts. At the same time, this drug inhibited the growth of tumors in vivo. Therefore, the new synthetic drug Caba-780 has potential applications in the diagnosis and treatment of CRPC. [ABSTRACT FROM AUTHOR]

Abnormal autonomic nervous system (ANS) function may result in poor outcomes in patients with schizophrenia. Altered cardio-respiratory coupling, which indicates suppression of vagal activity, was identified as an important trait in patients with schizophrenia and their unaffected relatives. Heart rate variability (HRV) in standardized bedside reflex tests has been studied, mostly in medicated patients with schizophrenia whose ANS function could be influenced by medication. Our study aimed to explore the autonomic function differences between drug-naïve patients with schizophrenia and healthy individuals during challenge tests combining respiration and HRV analysis. Forty-two drug-naïve patients with schizophrenia were matched with 42 healthy controls in terms of age and gender. Their beat-to-beat blood pressure and heart rate were monitored in the supine position as a survey of ANS function, and the mean heart rate range (MHRR) was measured under deep-breathing challenge. A decreased MHRR, a sensitive sign indicating an impaired parasympathetic response, during the deep-breathing challenge among the drug-naïve patients with schizophrenia was found. Drug-naïve patients with schizophrenia may have a parasympathetic dysfunction in the early stages of schizophrenia before medication is introduced, which could be considered a neurobiological marker in the pathophysiology of schizophrenia. [ABSTRACT FROM AUTHOR]

Aims: Nitrogen (N) application is often known to influence various properties in Chinese fir growth, but the regeneration failure and productivity decline in Chinese fir plantations are often affected by allelochemical compounds. Little is known about the interactive effect of allelochemicals and N sources on the plant growth in Chinese fir seedlings. Methods: Chinese fir seedlings were respectively subjected to the addition of ammonium (NH4+), nitrate (NO3−), p-hydroxybenzoic acid (pHBA) and their combined additions. Results: The pHBA addition alone promoted Chinese fir seedlings growth, but this effect was differentially affected by the interaction with NH4+ or NO3−. Both NH4+ and NO3− application improved plant growth, but the stimulatory effect of NO3− was weakened with addition of pHBA. Although NO3− addition combined with pHBA increased N accumulation in roots, the enzymes activities related to N assimilation were significantly decreased. These negative influences were also manifested through the decreased photosynthetic capacity, the reduction in photosynthates production and accumulation, and the destruction of chloroplast structural integrity. Moreover, the C/N ratio in root was obviously decreased and N assimilation was inhibited under the combined treatment of pHBA and NO3−, thereby aggravating C − N imbalance. Conclusions: The Chinese fir seedlings shifted their N uptake preference from NO3− to NH4+ when pHBA were added in soil. The dominant N source and allelochemicals interaction should be considered for Chinese fir growth. [ABSTRACT FROM AUTHOR]

Objective: To investigate the incidence of tubulointerstitial injury in lupus nephritis (LN) and to examine clinicopathological factors that could indicate the presence of tubulointerstitial injury. Methods: This study included 98 patients with LN. Clinical data and the pathological results of the initial renal biopsy were collected. Results: The frequency of each tubulointerstitial injury parameter was over 50%, except for the interstitial edema, in the 98 patients investigated in this study. The most frequently detected tubulointerstitial injury parameter was tubular atrophy in this study. Neutrophil infiltration/karyorrhexis, wire loop lesion, and arteriosclerosis were observed frequently in patients with tubulointerstitial injuries. High serum creatinine and blood urea nitrogen (BUN) were observed more frequently in patients with tubulointerstitial injuries except tubular degeneration. The multivariable regression analysis showed a relationship between neutrophil infiltration/karyorrhexis and interstitial fibrosis/tubular degeneration, a relationship between wire loop lesion and tubulointerstitial inflammation/edema, and a relationship between arteriosclerosis and tubulointerstitial injuries (except interstitial edema). Patients with tubular degeneration had lower D-Dimer levels compared with those without. Patients with interstitial fibrosis had higher blood leukocyte counts than those without. The rate of low response to therapy was 13% among those without tubulointerstitial inflammation, but 35% in those with interstitial inflammation (P = 0.03). Conclusion: Acute and chronic renal tubulointerstitial lesions are often found along with glomerular and vascular lesions. Immune and vascular factors are probably involved in tubulointerstitial injuries. Tubulointerstitial inflammation may be the initiator of chronic renal injury and may predict response to therapy. Key Points •To provide a theoretical basis for tubulointerstitial injury in LN. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to test the hypothesis that readily degradable Carbon (C) has contrasting effect on soil N autotrophic and heterotrophic nitrification, can stimulate nitrous oxide (N2O) emission. The knowledge can improve our understanding of the effect of readily degradable C on soil N nitrification and the related N2O emission. Materials and methods: 15N tracing technique along with acetylene inhibition was used to determine the effect of different doses of glucose-C addition on the rates of total nitrification (ntot), autotrophic nitrification (na), heterotrophic nitrification (nh), and N2O production in two soils. Soils were collected from Glenormiston (GN) and Terang (TR), Victoria, Australia and incubated at soil moisture content of 60% water-filled pore space (WFPS) and at 25 °C. Results and discussion: The addition of mixed C and N substrates with wide C/N ratio (> 25) promoted heterotrophic nitrification by 2.84- to 3.33-folds but inhibited autotrophic nitrification by 30.4–54.8%, thereby resulting in high ntot and NO3− accumulation compared with the soil samples under the control treatment. The mechanism of glucose inhibition of na might be caused by increasing the microbial immobilization of NH4+ and not by affecting the gene copy numbers of ammonia-oxidizing archea and ammonia-oxidizing bacteria. The glucose addition stimulated N2O production in soil, which might be caused by promoting heterotrophic nitrification and denitrification. Conclusions: The stimulating effect of degradable C application on the contribution of heterotrophic nitrification to total nitrification, NO3− accumulation, and N2O production should be considered, especially in soils with low pH and high organic C content. [ABSTRACT FROM AUTHOR]

Main conclusion: The 5-leaf-stage rape seedlings were more insensitive to Pi starvation than that of the 3-leaf-stage plants, which may be attributed to the higher expression levels of ethylene signaling and sugar-metabolism genes in more mature seedlings. Traditional suppression subtractive hybridization (SSH) and RNA-Seq usually screen out thousands of differentially expressed genes. However, identification of the most important regulators has not been performed to date. Here, we employed two methods, namely, a two-round SSH and two-factor transcriptome analysis derived from the two-factor ANOVA that is commonly used in the statistics, to identify development-associated inorganic phosphate (Pi) starvation-induced genes in Brassica napus. Several of these genes are related to ethylene signaling (such as EIN3, ACO3, ACS8, ERF1A, and ERF2) or sugar metabolism (such as ACC2, GH3, LHCB1.4, XTH4, and SUS2). Although sucrose and ethylene may counteract each other at the biosynthetic level, they may also work synergistically on Pi-starvation-induced gene expression (such as PT1, PT2, RNS1, ACP5, AT4, and IPS1) and root acid phosphatase activation. Furthermore, three new transcription factors that are responsive to Pi starvation were identified: the zinc-finger MYND domain-containing protein 15 (MYND), a Magonashi family protein (MAGO), and a B-box zinc-finger family salt-tolerance protein. This study indicates that the two methods are highly efficient for functional gene screening in non-model organisms. [ABSTRACT FROM AUTHOR]

Multi-level ditch area is a major component of the hydrographic net of plain area, China. Given the high concentration of nitrogen (N) in the surface water and vigorous biogeochemical interactions, ditch is likely to be the hot spots of N2O emission. However, N2O emission flux and emission factor (EF5r) of multi-level ditches have not been determined. To address this knowledge gap, a 1-year field work in three ditches with different levels in Chengdu Plain was conducted. It is found that the annual flux of N2O emission and EF5r was higher in the lateral (0.0020 and 83.94 μg m−2 h−1) and field ditches (0.0019 and 110.75 μg m−2 h−1) than in the branch ditch (0.0016 and 46.38 μg m−2 h−1, P < 0.05). It is found that parameters of groundwater level, discharge, precipitation, and NH4+ were the primary factors, and these parameters can model the N2O flux well. Furthermore, the content of NH4+ in the surface water of ditches presented better correlation with the emission of N2O than the content of NO3−. Therefore, controlling NH4+ emission and lessening fertilizer usage in summer may be key solutions for indirect reduction of N2O in Chengdu Plain. [ABSTRACT FROM AUTHOR]

We report a correlative study of strain distribution and grain structure in the Al matrix of a hot-extruded SiC particulate-reinforced Al composite (SiCp/2014 A1). Finite element method (FEM) simulation and microstructure characterization indicate that the grain structure of the Al matrix is affected by the interparticulate strain distribution in the matrix during the process. Both electron-backscattered diffraction (EBSD) and selected-area electron diffraction (SAED) indicated localized misorientation in the Al matrix after hot extrusion. Scanning transmission electron microscopy (STEM) revealed fine and recrystallized grains adjacent to the SiC particulate and elongated grains between the particulates. This result is explained in terms of recrystallization under an interparticulate strain distribution during the hot extrusion process. [ABSTRACT FROM AUTHOR]

Australian pasture soil for cattle and sheep industries constitutes the principal land use with considerable N fertilizer consumption, which is one of the causes of local environmental problems. Nitrification plays a key role in regulating soil inorganic N concentration and its environmental diffusion. The effects of different nitrification inhibitors (NIs) on gross N nitrification (ngross) rate and N2O production under different temperatures in pasture soils remain unclear. A laboratory incubation experiment was conducted to determine the effect of NIs (dicyandiamide [DCD], 3,4-dimethylpyrazole phosphate [DMPP], and 3-methylpyrazol and 1H-1,2,4-triazol [3MP + TZ]) on N2O emissions, ngross and net N nitrification (nnet) rates, and the abundance of ammonia oxidizers, namely, ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB), in two Australian pasture soils incubated at temperatures of 15, 25, and 35 °C. All NIs reduced both ngross and nnet rates and N2O production rate from the two pasture soils but to different extents. The inhibitory rates of NIs on ngross and nnet reached 6.80-63.8 and 5.91-62.3%, respectively, whereas that on N2O production rate totaled 4.5-41.4% in the tested soils. NIs reduced nitrification and N2O production by inhibiting the growth of AOB rather than AOA. The inhibitory effects of NIs were temperature-dependent, that is, decreasing with increasing temperature from 15 to 35 °C. In general, DMPP performed better than DCD and 3MP + TZ at 15 and 35 °C, whereas DCD performed more effectively than the other two NIs at 25 °C. Our results suggest that the utilization of NIs will depend on the conditions present, especially soil temperature. Additionally, AOB is the target of inhibition when mitigating nitrification and N2O emission by applying NIs in pasture soils. [ABSTRACT FROM AUTHOR]

CRISPR/Cpf1 features a number of properties that are distinct from CRISPR/Cas9 and provides an excellent alternative to Cas9 for genome editing. To date, genome engineering by CRISPR/Cpf1 has been reported only in human cells and mouse embryos of mammalian systems and its efficiency is ultimately lower than that of Cas9 proteins from Streptococcus pyogenes. The application of CRISPR/Cpf1 for targeted mutagenesis in other animal models has not been successfully verified. In this study, we designed and optimized a guide RNA (gRNA) transcription system by inserting a transfer RNA precursor (pre-tRNA) sequence downstream of the gRNA for Cpf1, protecting gRNA from immediate digestion by 3′-to-5′ exonucleases. Using this new gRNAtRNA system, genome editing, including indels, large fragment deletion and precise point mutation, was induced in mammalian systems, showing significantly higher efficiency than the original Cpf1-gRNA system. With this system, gene-modified rabbits and pigs were generated by embryo injection or somatic cell nuclear transfer (SCNT) with an efficiency comparable to that of the Cas9 gRNA system. These results demonstrated that this refined gRNAtRNA system can boost the targeting capability of CRISPR/Cpf1 toolkits. [ABSTRACT FROM AUTHOR]

Purpose: Better understanding of N transformations and the regulation of N2O-related N transformation processes in pasture soil contributes significantly to N fertilizer management and development of targeted mitigation strategies.Materials and methods: 15N tracer technique combined with acetylene (C2H2) method was used to measure gross N transformation rates and to distinguish pathways of N2O production in two Australian pasture soils. The soils were collected from Glenormiston (GN) and Terang (TR), Victoria, Australia, and incubated at a soil moisture content of 60% water-filled pore space (WFPS) and at temperature of 20 °C.Results and discussion: Two tested pasture soils were characterized by high mineralization and immobilization turnover. The average gross N nitrification rate (ntot) was 7.28 mg N kg−1 day−1 in TR soil () and 5.79 mg N kg−1 day−1 in GN soil. Heterotrophic nitrification rates (nh), which accounting for 50.8 and 41.9% of ntot, and 23.4 and 30.1% of N2O emissions in GN and TR soils, respectively, played a role similar with autotrophic nitrification in total nitrification and N2O emission. Denitrification rates in two pasture soils were as low as 0.003-0.004 mg N kg−1 day−1 under selected conditions but contributed more than 30% of N2O emissions.Conclusions: Results demonstrated that two tested pasture soils were characterized by fast N transformation rates of mineralization, immobilization, and nitrification. Heterotrophic nitrification could be an important NO3−-N production transformation process in studied pasture soils. Except for autotrophic nitrification, roles of heterotrophic nitrification and denitrification in N2O emission in two pasture soils should be considered when developing mitigation strategies. [ABSTRACT FROM AUTHOR]

Outdoor pot and field experiments were conducted to study the effect of controlled-release fertilizer (CRF) on nitrous oxide (N2O) and nitric oxide (NO) emissions and wheat yields during the 2011-2013. Three treatments, namely conventional N fertilizer (CF; urea and compound fertilizer, 300 kg N ha−1), CRF (210 kg N ha−1, which is 70% of the N applied in the CF treatment), and check (CK, 0 N), were applied in three replicates. The soil temperature, soil moisture, N uptake by wheat, wheat yield, and variations in NO3-N, NH4-N, N2O, and NO emissions were measured. Results showed that the average total N2O and NO emissions in the CRF treatment in the pot and field experiments decreased by 26.5 and 19.4%, respectively. The average N2O and NO emission factors decreased by 32.1 and 24.8%, respectively, compared with the CF treatment. However, the CRF wheat yields were insignificantly lower than those from the CF treatment. Results indicated that CRF could improve the efficiency of fertilizer N use, reduce labor cost, and increase economic benefit without sacrificing the yield. [ABSTRACT FROM AUTHOR]

The phenomenon of losing a green signal in synovial sarcoma (SS) using the SS18 break-apart probe by fluorescence in situ hybridization (FISH) has been poorly described. In this study, 12 SS with missing a green signal were identified. This series included 7 males and 5 females, aged 17 to 69 years (median, 38.5 years). The tumors involved the extremities (50%), mediastinum (16.7%), hypopharynx (8.3%), neck (8.3%), thyroid (8.3%), and retroperitoneum (8.3%). The tumors were classified as monophasic SS (58.3%) and poorly differentiated SS (41.7%). An anaplastic SS showing features of pleomorphic sarcoma was observed. Immunostaining for TLE1, BCL2, CD99, epithelial membrane antigen, cytokeratin (AE1/AE3), cytokeratin 7, S-100 protein, and CD34 was consistent with typical SS. In FISH, all the tumors showed the pattern of 1 to 3 fused signal(s) with 1 to 3 red signal(s), without corresponding a green signal. The fusion transcripts included SS18-SSX1 (8/10, 80%) and SS18-SSX2 (2/10, 20%) fusions. Median and 5-year overall survival were 19.1 months and 43.6%, respectively. In conclusion, we reported a series of SS losing a green signal in the SS18 FISH assay. We propose that this variant FISH pattern should be interpreted as a peculiar unbalanced rearrangement of the SS18 gene and subsequent SS18-SSX fusion test should be recommended. The cases in this study seem to show some unusual clinicopathological features, including unusual locations, higher proportions of poorly differentiated SS, and aggressive clinical course. However, whether this variant FISH pattern is associated with peculiar clinicopathologic features awaits larger series. [ABSTRACT FROM AUTHOR]

The NLRP3 inflammasome is an intracellular multiple-protein complex that controls the maturation and release of interleukin (IL)-1β and IL-18. Endogenous carbon monoxide (CO) is anti-inflammatory. The aim of this study was to assess the effects/mechanisms of CO-releasing molecule-3 (CORM-3)-dependent modulation of the NLRP3 inflammasome in cardiac fibroblasts (CF) and its effect on myocardial function in sepsis. CF were treated with CORM-3 or inactive CORM-3 (iCORM-3) before NLRP3 inflammasome priming with lipopolysaccharides (LPS) or following activation with adenosine triphosphate (ATP). In parallel, cardiomyocytes (CM) were challenged with supernatants of LPS/ATP-stimulated CF or a cytokine mixture (Cyto-mix) containing IL-1β, IL-18, and HMGB1. In vivo, mice were treated with CORM-3 before or after LPS to induce sepsis (endotoxemia). Pretreatment of CF with CORM-3 prevented an LPS-induced increase in NLRP3 and pro-IL-1β expression. Treatment of CF with CORM-3 before ATP prevented ATP-induced activation of the NLRP3 inflammasome. Challenging CF with LPS/ATP promoted NLRP3 interactions with adaptor ASC (apoptosis-associated speck-like protein containing a caspase-recruitment domain), which was prevented by CORM-3. Challenging CM with supernatants of CF with LPS/ATP or Cyto-mix (IL-1β, IL-18, and HMGB1) resulted in CM apoptosis, which was attenuated with either a CORM-3 or IL-1 receptor antagonist. Finally, myocardial NLRP3 inflammasome activation and myocardial dysfunction in septic mice were abolished by CORM-3. In NLRP3-deficient mice with sepsis, CORM-3 did not show additional benefits in improving myocardial function. Our results indicate that CORM-3 suppresses NLRP3 inflammasome activation by blocking NLRP3 interactions with the adaptor protein ASC and attenuates myocardial dysfunction in mice with sepsis. [ABSTRACT FROM AUTHOR]

Purpose: Cisplatin can cause a variety of DNA crosslink lesions including intra-strand and inter-strand crosslinks (ICLs), which are associated with the sensitivity of cancer cells to cisplatin. Here, we aimed to assess the contribution of the Fanconi anemia (FA), homologous recombination (HR) and nucleotide excision repair (NER) pathways to cisplatin resistance in non-small cell lung cancer (NSCLC)-derived cells. Methods: The expression of FA, HR and NER pathway-associated genes was assessed by RT-qPCR and Western blotting. siRNAs were used to knock down the expression of these genes. CCK-8 and flow cytometry assays were used to assess the viability and apoptotic rate of NSCLC-derived cells, respectively. Immunofluorescence and alkaline comet assays were used to assess the repair of ICLs. Results: We found that acquired cisplatin-resistant NSCLC-derived A549/DR cells exhibited markedly enhanced FA and HR repair pathway capacities compared to its parental A549 cells and another independent NSCLC-derived cell line, Calu-1, which possesses a moderate innate resistance to cisplatin. siRNA-mediated silencing of the FA-associated genes FANCL and RAD18 and the HR-associated genes BRCA1 and BRCA2 significantly potentiated the sensitivity of A549/DR cells to cisplatin compared to A549 and Calu-1 cells, suggesting that the acquired cisplatin resistance in A549/DR cells may be attributed to enhanced FA and HR pathway capacities responsible for ICL repair. Although we found that expression knockdown of the NER-associated genes XPA and ERCC1 sensitized the three NSCLC-derived cell lines to cisplatin, the sensitization effect was more significant in Calu-1 cells than in A549 and A549/DR cells, implying that the innate cisplatin resistance in Calu-1 cells may result from an increased NER activity. Conclusions: Our results indicate that the functional status of DNA repair pathways determine the sensitivity of NSCLC cells to cisplatin. Direct targeting of the pathway that is involved in cisplatin resistance may be an effective strategy to surmount cisplatin resistance in NSCLC. [ABSTRACT FROM AUTHOR]

A young male flower-derived embryogenic suspension cell population of AAA 'Pei Chiao', 'Dwarf Cavendish', and AAB 'Raja' was used for developing an acidogenic growth model . We hypothesized that a close relationship exists between the self-regulated pH medium and the corresponding changes in the growth phases. Studies have reported that a pH below 4.6 may prevent the embryogenic cells from undergoing polar growth. Controlling pH up to a level 4.6 within 2 days during the changes of pre-embryogenic cells (PECs) and proembryogenic masses into embryogenic determined cells (EDCs) uniformly resulted in unequal cell division. The hydrogen ion buffer 2-N-morpholino-ethanesulfonic acid at 10 g L was added to MA2 and MA3 media, showing the medium pH of MA3 up to 5.0, thus maintaining a relatively stable pH in AAA 'Pei-Chiao' and AAB 'Raja' cells that autoregulate acidification, significantly increasing the number of somatic embryos. When the proliferation and globularization phases were acidified to pH 3.5 ± 0.2, cells were released to free single cells of PECs and EDCs after 21 days. This study provides possible explanation that PECs deposit callose on their cell walls as a possible protector from strong acidic condition. Regulation at pH 5.0 ± 0.2 resulted the production efficiency achieved was 0.9 million somatic embryos per 1 mL of the settled cell volume. [ABSTRACT FROM AUTHOR]

Cisplatin (DDP) is the most widely used chemotherapy agent for treatment of malignancies including lung cancer. However, the effectiveness of DDP is often weakened by acquired resistance of tumor cells. DDP kills cancer cells primarily by creating intrastrand and interstrand DNA cross-links, which block DNA replication. The Fanconi anemia (FA)/BRCA pathway is a DNA cross-link damage repair pathway, which regulates cellular resistance to DNA cross-link agents, such as DDP. Some study has shown that natural compound curcumin sensitize human ovarian and breast cancer cells to DDP. However, whether curcumin may reverse resistance to DDP in DDP-resistant lung cancer cells has not been understood. In this study, we showed that curcumin enhanced the proliferation inhibitory effect of DDP and promote DDP-induced apoptosis in A549/DDP cells (DDP-resistant lung adenocarcinoma cells). Moreover, we observed that FA/BRCA pathway DNA damage repair processes, such as DDP-induced FANCD monoubiquitination and nuclear foci formation were downregulated in the presence of curcumin, suggesting that curcumin enhanced sensitivity to DDP in A549/DDP cells through the inhibition of FA/BRCA pathway. Furthermore, the calculation of q value and apoptosis analyses revealed that curcumin in combination with DDP could exert a synergistic cytotoxic effect in A549/DDP cells, further demonstrating that curcumin can reverse cisplatin resistance of A549/DDP cells. In conclusion, by suppressing the FA/BRCA pathway DNA repair, curcumin potentiates DDP-induced proliferation inhibitory effect and apoptosis in A549/DDP cell, indicating that curcumin may serve as a chemosensitizer to cross-link-inducing anticancer drugs DDP. [ABSTRACT FROM AUTHOR]

Purpose: In the rice soils, the alternate wetting and drying conditions and the leakage of O from rice roots provides a favorable environment for many N transformation processes, such as DNRA, nitrification, mineralization, and denitrification. Since nitrification is an inevitable process providing available NO for DNRA and other NO loss pathways, it is logical to hypothesize that a relationship exists between nitrification and DNRA. Thus, we quantified the specific gross N transformation rates occurring simultaneously to investigate the correlation among the N transformation rates in the rice soil. Material and methods: In this study, three rice soils with different pH values were selected. The combination of N tracing experiment and numerical modeling method was performed to quantify the specific gross N transformation rates (e.g., DNRA), to analyze the correlation between DNRA and the other N transformations, and to estimate the functional role of DNRA comparing to other N transformation in the rice soil. Results and discussion: The results showed that there were two NH production pathways, organic N mineralization and DNRA, in the neutral (pH 6.2) and alkaline (pH 8.2) soils, while the DNRA process was negligible in acidic soil (pH 4.7). The mineralization rate in the acidic soil (2.69 mg kgd) was significantly higher than that in neutral and alkaline soils. The DNRA rate was 0.48 and 1.09 mg kgd, which was almost equal to the mineralization rate, in the neutral (pH 6.2) and alkaline (pH 8.2) soils, offsetting efficiently the effect of low mineralization on N availability in ecosystems. The DNRA rate linearly increased with the increase in gross nitrification rate ( p < 0.05). This significant coupling relationship between DNRA and nitrification favors N conservation and availability for paddy growth in the rice ecosystem. Conclusions: DNRA plays an important role in soil N conservation and availability in neutral and alkaline but not acidic rice soil. [ABSTRACT FROM AUTHOR]

Denitrification and its products composition were evaluated in four typical Chinese paddy soils with pH (HO) ranging from 4.80 to 8.29 after application of 50 or 100 mg kg soil KNO and subsequent anaerobic incubation. Denitrification rates, which were indicated by nitric oxide (NO), nitrous oxide (NO), and dinitrogen gas (N) production, significantly varied among different paddy soils. The denitrification rates of the neutral and alkaline paddy soils were 2.6 to 16.6 times higher, respectively, than those of acidic paddies. Furthermore, denitrification in paddy soils could produce end products other than N, and the product composition depended on the paddy soil type. The percentage of total N gases (NO + NO + N) present as NO was negatively and linearly correlated with denitrification rate ( P < 0.05). Soil pH and C/N showed positive effects on denitrification rate ( r = 0.800 and r = 0.781, respectively, P < 0.05 for both), but negative effects on the percentage of total N gases present as NO ( r = −0.976, P < 0.01 and r = −0.781, P < 0.05, respectively). Denitrification rate and the percentage of total gases present as NO increased as the nitrate (NO) concentration increased. However, there was no effect of NO concentration on the percentage of total N gases present as NO. Our results indicate that the potential N loss through denitrification may be higher in alkaline paddies than that in neutral and acidic paddies. Moreover, the variation of the NO percentage in denitrification products of different paddy soils should be considered when estimating the denitrification-derived NO emission and when calculating the N budget in paddy soils. [ABSTRACT FROM AUTHOR]