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Gastric cancer (GC) has become the first malignant tumor with highest incidence rate and mortality of cancer in China, finding therapeutic targets for gastric cancer is of great significant for improving the survival rate of patients with GC. Recently, many of studies have shown that LncRNAs is involved in multiple biological progresses in the development of GC. This study, we screened for abnormally high expression of LncSHANK3 in GC through the TCGA database, and found that LncSHANK3 sponge adsorbs miR-4530, further competing with MNX1 and binding to miR-4530. We demonstrated the interaction between LncSHANK3 and miR-4530 through luciferase reporting analysis, with miR-4530 negatively regulating MNX1.Through CCK8, colony formation, transwell, and wound healing assays, it was found that LncSHANK3 affects the occurrence of GC through cell proliferation, migration and invasion. In conclusion, LncSHANK3/miR-4530/MNX1 axis is a potential mechanism for the treatment of GC.

Sex determination in plants gives rise to unisexual flowers. A better understanding of the regulatory mechanism underlying the production of unisexual flowers will help to clarify the process of sex determination in plants and allow researchers and farmers to harness heterosis. Androecious cucumber (Cucumis sativus L.) plants can be used as the male parent when planted alongside a gynoecious line to produce heterozygous seeds, thus reducing the cost of seed production. The isolation and characterization of additional androecious genotypes in varied backgrounds will increase the pool of available germplasm for breeding. Here, we discovered an androecious mutant in a previously generated ethyl methanesulfonate (EMS)-mutagenized library of the cucumber inbred line ‘406’. Genetic analysis, whole-genome resequencing, and molecular marker-assisted verification demonstrated that a nonsynonymous mutation in the ethylene biosynthetic gene 1-AMINOCYCLOPROPANE-1-CARBOXYLATE SYNTHASE 11 (ACS11) conferred androecy. The mutation caused an amino acid change from serine (Ser) to phenylalanine (Phe) at position 301 (S301F). In vitro enzyme activity assays revealed that this S301F mutation leads to a complete loss of enzymatic activity. This study provides a new germplasm for use in cucumber breeding as the androecious male parent, and it offers new insights into the catalytic mechanism of ACS enzymes.

Combined application of chemical fertilizers with organic amendments was recommended as a strategy for improving yield, soil carbon storage, and nutrient use efficiency. However, how the long-term substitution of chemical fertilizer with organic manure affects rice yield, carbon sequestration rate (CSR), and nitrogen use efficiency (NUE) while ensuring environmental safety remains unclear. This study assessed the long-term effect of substituting chemical fertilizer with organic manure on rice yield, CSR, and NUE. It also determined the optimum substitution ratio in the acidic soil of southern China. The treatments were: (i) NPK0, unfertilized control; (ii) NPK1, 100% chemical nitrogen, phosphorus, and potassium fertilizer; (iii) NPKM1, 70% chemical NPK fertilizer and 30% organic manure; (iv) NPKM2, 50% chemical NPK fertilizer and 50% organic manure; and (v) NPKM3, 30% chemical NPK fertilizer and 70% organic manure. Milk vetch and pig manure were sources of manure for early and late rice seasons, respectively. The result showed that SOC content was higher in NPKM1, NPKM2, and NPKM3 treatments than in NPK0 and NPK1 treatments. The carbon sequestration rate increased by 140, 160, and 280% under NPKM1, NPKM2, and NPKM3 treatments, respectively, compared to NPK1 treatment. Grain yield was 86.1, 93.1, 93.6, and 96.5% higher under NPK1, NPKM1, NPKM2, and NPKM3 treatments, respectively, compared to NPK0 treatment. The NUE in NPKM1, NPKM2, and NPKM3 treatments was higher as compared to NPK1 treatment for both rice seasons. Redundancy analysis revealed close positive relationships of CSR with C input, total N, soil C:N ratio, catalase, and humic acids, whereas NUE was closely related to grain yield, grain N content, and phenol oxidase. Furthermore, CSR and NUE negatively correlated with humin acid and soil C:P and N:P ratios. The technique for order of preference by similarity to ideal solution (TOPSIS) showed that NPKM3 treatment was the optimum strategy for improving CSR and NUE. Therefore, substituting 70% of chemical fertilizer with organic manure could be the best management option for increasing CSR and NUE in the paddy fields of southern China.

Fertilization is an effective technique to improve soil fertility and increase crop yield. The long-term effects of different fertilizers on soil considerably vary. Over 38 consecutive years of different fertilization positioning experiments in a double cropping rice field of Qiyang Red Soil Experimental Station, seven different fertilization treatments including CK (no fertilization), NPK (nitrogen, phosphorus, and potassium fertilizer), M (cow manure), NPKM (nitrogen, phosphorus, and potassium with cow manure), NPM (nitrogen and phosphorus with cow manure), NKM (nitrogen and potassium with cow manure), and PKM (phosphorus and potassium with cow manure) were applied to study the effects on rice yield, soil fertility, and nutrient apparent balance in a paddy field. The results showed that the annual average yields of rice in NPKM, NPM, NKM, PKM, M, NPK and CK treatments ranged from 6 214 to 11 562 kg ha–1. Yields under long-term organic and inorganic treatments (NPKM, NPM, NKM and PKM) were 22.58, 15.35, 10.53 and 4.41%, respectively, greater than under the NPK treatment. Soil organic carbon (SOC), total nitrogen (TN), available nitrogen (AN) and available potassium (AK) concentration with long-term organic and inorganic treatment (NPKM, NPM, NKM and PKM) were significantly higher than in inorganic fertilizer (NPK) treatments. Soil total phosphorus (TP) and available phosphorus (AP) contentration with organic fertilizer combined with inorganic N and P fertilizer treatment (NPKM, NPM and PKM) were significantly higher than with inorganic fertilizer alone (NPK treatments). The average annual rice yield (11 562 kg ha–1), SOC (20.88 g kg–1), TN (2.30 g kg–1), TP (0.95 g kg–1), TK (22.50 g kg–1) and AP (38.94 mg kg–1) concentrations were the highest in the NPKM treatment. The soil AN concentration (152.40 mg kg–1) and AK contentration (151.00 mg kg–1) were the highest in the NKM treatment. N and P application led to a surplus of nitrogen and phosphorus in the soil, but NPKM treatment effectively reduced the surplus compared with other treatments. Soils under all treatments were deficient in potassium. Correlation analysis showed that SOC, TN, AN, TP, and AP contentration was significantly correlated with rice yield; the correlation coefficients were 0.428, 0.496, 0.518, 0.501, and 0.438, respectively. This study showed that the combined application of N, P, and K with cow manure had important effects on rice yield and soil fertility, but balanced application of N, P, and K with cow manure was required.

In situ mRNA hybridization (ISH) is a powerful tool for examining the spatiotemporal expression of genes in shoot apical meristems and flower buds of cucumber. The most common ISH protocol uses paraffin wax; however, embedding tissue in paraffin wax can take a long time and might result in RNA degradation and decreased signals. Here, we developed an optimized protocol to simplify the process and improve RNA sensitivity. We combined embedding tissue in low melting-point Steedman's wax with processing tissue sections in solution, as in the whole-mount ISH method in the optimized protocol. Using the optimized protocol, we examined the expression patterns of the CLAVATA3 (CLV3) and WUSCHEL (WUS) genes in shoot apical meristems and floral meristems of Cucumis sativus (cucumber) and Arabidopsis thaliana (Arabidopsis). The optimized protocol saved 4–5 days of experimental period compared with the standard ISH protocol using paraffin wax. Moreover, the optimized protocol achieved high signal sensitivity. The optimized protocol was successful for both cucumber and Arabidopsis, which indicates it might have general applicability to most plants.

Abstract Aldolase A (ALDOA), an important metabolic enzyme in the glycolytic pathway, plays an important role in regulating tumour metabolism. In this study, we investigated the expression pattern of ALDOA in hepatocellular carcinoma (HCC) and its biological role in tumour progression. Bioinformatics analysis, western blot (WB) and RT-qPCR were performed to detect the relative expression of ALDOA in HCC tissues and cell lines. A loss-of-function approach was used to investigate the biological function of ALDOA. The role of ALDOA on glycolysis was assessed by WB, glucose and lactate assay kits and a nude mouse xenograft model. Luciferase reporter experiment, chromatin immunoprecipitation and WB were performed to elucidate the underlying molecular. The expression level of ALODA was up-regulated in HCC tissues and cell lines. High ALDOA levels were associated with poorer patient overall survival. Mechanistic studies suggest that ALDOA is a direct target of miR-34a-5p, which can inhibit glycolysis in hepatocellular carcinoma cells by targeting the 3′UTR of ALDOA. PINK1 antisense RNA (PINK1-AS) competitively sponged miR-34a-5p to increase ALDOA expression by antagonizing miR-34a-5p-mediated ALDOA inhibition. MKL-1 acted as a transcription factor to promote the expression of PINK1-AS and ALDOA, thus promoting the deterioration of HCC cells. This study shows that high expression of ALDOA contributes to the development and poor prognosis of hepatocellular carcinoma and will be a target and potential prognostic biomarker for the treatment of HCC.

Abstract Background Long non-coding RNAs (lncRNAs) are closely related to the occurrence and development of cancer. Abnormally expressed lncRNA can be used as a diagnostic marker for cancer. In this study, we aim to investigate the clinical significance of MIR99AHG expression in lung adenocarcinoma (LUAD), and its biological roles in LUAD progression. Methods The relative expression of MIR99AHG in LUAD tissues and cell lines was analyzed using public databases and RT-qPCR. The biological functions of MIR99AHG were investigated using a loss-of-function approach. The effect of MIR99AHG on lung fibrosis was assessed by scratch assay, invasion assay and lung fibrosis rat model. FISH, luciferase reporter assay and immunofluorescence were performed to elucidate the underlying molecular mechanisms. Results LncRNA MIR99AHG expression level was downregulated in LUAD tissues and cell lines. Low MIR99AHG levels were associated with poorer patient overall survival. Functional analysis showed that MIR99AHG is associated with the LUAD malignant phenotype in vitro and in vivo. Further mechanistic studies showed that, MIR99AHG functions as a competitive endogenous RNA (ceRNA) to antagonize miR-136-5p-mediated ubiquitin specific protease 4 (USP4) degradation, thereby unregulated the expression of angiotensin-converting enzyme 2 (ACE2), a downstream target gene of USP4, which in turn affected alveolar type II epithelial cell fibrosis and epithelial–mesenchymal transition (EMT). In summary, the MIR99AHG/miR-136-5p/USP4/ACE2 signalling axis regulates lung fibrosis and EMT, thus inhibiting LUAD progression. Conclusion This study showed that downregulated MIR99AHG leads to the development of pulmonary fibrosis. Therefore, overexpression of MIR99AHG may provide a new approach to preventing LUAD progression.

Understanding the impact of biological activities on the soil phosphorus (P) distribution under long-term fertilizer application can facilitate better soil P fertility management. Therefore, the primary objectives of this study were to investigate the effect of long-term (since 1981) fertilizer application on the soil P fractions and microbial community and to evaluate correlations between the microbial community structure and P distribution. The following treatments were implemented in a long-term field trial: no fertilization (CK), inorganic N and K (NK), inorganic P and K (PK), inorganic N, P and K (NPK) and manure+NPK (MNPK) fertilization. The study showed that the soil pH, soil organic carbon and total and available N and P concentrations were considerably higher in the MNPK treatment than in the CK treatment. The soil microbial biomass C, N and P concentrations were also significantly higher in the MNPK treatment than in the CK treatment. Among fertilization treatments, the β-1,4-glucosidase, α-1,4-glucosidase, urease, acid phosphatase and phosphodiesterase activities were the highest in the MNPK treatment. Compared to inorganic fertilization, the MNPK treatment increased the labile soil P fractions and decreased the residual soil P concentration. Continuous fertilization significantly affected the soil microbial composition. The total phospholipid fatty acid (PLFA) concentrations in the NK, PK, NPK and MNPK treatments were 23.3, 43.1, 48.7 and 87.7% higher, respectively, than in the CK treatment. A significant correlation was observed between the microbial community and soil P fractions. Moreover, the aggregated boosted tree (ABT) model showed that among the various soil biochemical properties, the total PLFA concentration was the factor that most influenced the active P pool, accounting for 35.4% of the relative influence of all soil biochemical properties examined. These findings reveal that combined manure and inorganic fertilizer application is a better approach than applying inorganic fertilizer alone for sustaining long-term P fertility by mediating soil biological activity.

Currently, it is most economical to transport hydrogen with the existing natural gas pipelines by blending it into the natural gas among the storage and transportation technologies of hydrogen energy, and thus the transportation technology of hydrogen-blended natural gas is widely concerned by research institutes at home and abroad. However, hydrogen embrittlement may be caused to the pipeline steel due to the contact of hydrogen with base metal during hydrogen transportation, which further leads to the deterioration of mechanical properties of pipeline steel, threatening the safe operation of pipelines. Therefore, the change law of the mechanical properties of X52 and X80 steel typically used for natural gas pipelines under the actual hydrogen-blended conditions was studied through in-situ tensile testing and fracture morphology analysis under the environment of high-pressure gas-phase hydrogen. Meanwhile, the influence of hydrogen partial pressure on yield strength, tensile strength, percentage reduction of area and hydrogen embrittlement index of material was analyzed. The study results show that, the ductility of X52 and X80 steel is declined and the hydrogen embrittlement is intensified with the increasing of hydrogen partial pressure. Compared with X80 steel, X52 steel is more suitable for the hydrogen-blended natural gas transportation. Generally, the study results could provide reference to the material selection and safe operation of hydrogen-blended natural gas pipelines in the future.

Abstract Background Orosomucoid (ORM) is a positive acute phase protein verified to be upregulated in various forms of exercise-induced fatigued (EIF) rodents. However, its association with EIF among human beings remained unknown. This study aimed to explore the association between serum ORM and EIF triggered by military basic combat training (BCT). Methods The degree of EIF were measured by Borg’s Rating of Perceived Exertion Scale (Borg-RPE-Scale®) as RPE score after BCT. Fifty-three male recruits were classified into three groups according to the RPE score: (1) group 1 (slight fatigue group): RPE score after BCT 14. The levels of blood ORM, lactate (LAC), cortisol and C-reactive protein (CRP) were determined before and after BCT. The diagnostic value of ORM was evaluated by receiver operating characteristic (ROC) curve analysis and logistic regression. Results After BCT, the level of LAC, CRP, and cortisol increased among all groups, but the changes had no significant between-group difference (all p > 0.05). The level of ORM had a specific significant increase in group 3 (p = 0.039), and the changes of ORM (ΔORM) had significant difference among groups (p = 0.033). ROC curve analysis showed that the estimated area under ROC curve for ΔORM was 0.724 (p = 0.009) with the recommended optimal cut-off value as 0.2565 mg/mL. Logistic analysis showed that recruits with ΔORM ≥ 0.2565 mg/mL had higher odds for suffering from severe EIF, 5.625 times (95% CI 1.542–20.523, p = 0.009) as large as those with ΔORM

Soil organic carbon (SOC) and nitrogen (N) are two of the most important indicators for agricultural productivity. The primary objective of this study was to investigate the changes in SOC and N in the deep soil profile (up to 100 cm) and their relationships with crop productivity under the influence of long-term (since 1990) fertilization in the wheat-maize cropping system. Treatments included CK (control), NP (inorganic N and phosphorus (P) fertilizers), NPK (inorganic N, P and potassium fertilizers), NPKM (NPK plus manure), and M (manure). Crop yield and the properties of topsoil were measured yearly from 2001 to 2009. C and N contents were measured at five different depths in 2001 and 2009. The results showed that wheat and maize yields decreased between 2001 and 2009 under the inorganic fertilizer (NP and NPK) treatments. The average yield between 2001 and 2009 under the NP, NPK, NPKM, and M treatments (compared with the CK treatment) increased by 38, 115, 383, and 381%, respectively, for wheat and 348, 891, 2 738, and 1 845%, respectively, for maize. Different long-term fertilization treatments significantly changed coarse free particulate (cfPOC), fine free particulate (ffPOC), intramicroaggregate particulate (iPOC), and mineral-associated (mSOC) organic carbon fractions. In the experimental years of 2001 and 2009, soil fractions occurred in the following order for all treatments: mSOC>cfPOC>iPOC>ffPOC. All fractions were higher under the manure application treatments than under the inorganic fertilization treatments. Compared to the inorganic fertilization treatments, manure input enhanced the stocks of SOC and total N in the surface layer (0–20 cm) but decreased SOC and N in the deep soil layer (80–100 cm). This reveals the efficiency of manure in increasing yield productivity and decreasing risk of vertical loss of nutrients, especially N, compared to inorganic fertilization treatments. The findings provide opportunities for understanding deep soil C and N dynamics, which could help mitigate climate change impact on agricultural production and maintain soil health.

The soil-borne necrotrophic fungus Rhizoctonia solani is one of destructive fungi causing severe yield losses in various important crops. However, the host defense mechanisms against the invasion of this pathogen are poorly understood. In this study, we employed an iTRAQ-based quantitative proteomic approach to investigate host proteins responsive to R. solani using the resistant rice cultivar YSBR1. As a whole, we identified 319 differentially accumulated proteins (DAPs) after inoculation of rice plants with R. solani. Functional categorization analysis indicates that these DAPs cover a broad range of functions. Notably, a substantial portion of the DAPs are involved in cell redox homeostasis, carbohydrate metabolism, and phenylpropanoid biosynthesis, or belong to pathogenesis-related proteins, indicating that these processes/proteins play important roles in host defense against R. solani. Interestingly, all of the DAPs involved in photosynthesis and chlorophyll biosynthetic processes, and part of the DAPs involved in phenylpropanoid biosynthesis, show reduced accumulation after R. solani infection, suggesting that R. solani probably inhibits host photosynthetic system and phenylpropanoid biosynthesis to facilitate infection and colonization. In conclusion, our results provide both valuable resources and new insights into the molecular mechanisms underlying rice and R. solani interaction.

Crude sophorolipids (SLs) have been proven to perform varying degrees of inhibitory effects on different pathogenic bacteria. However, systematic comparative studies of pure lactonic sophorolipid (LSL) among different types of bacteria are few. In this study, the antibacterial effects and mechanisms of LSL on pathogenic bacteria of Staphylococcus aureus, Lactobacillus sp., Pseudomonas aeruginosa, and Escherichia coli were investigated. Bacteriostatic circle, antibacterial rate, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) of LSL on different pathogenic bacteria were measured. Then, the antibacterial mechanisms of LSL on S. aureus and P. aeruginosa were explored using ultrastructural observation, cell membrane permeability analysis, intracellular ATP content determination, and extracellular UV absorption detection. With the minimum MIC and MBC values of 0.05 and 0.20 mg/ml, LSL exhibited the best inhibitory effect against S. aureus, followed by P. aeruginosa. LSL showed no significant inhibitory effect on E. coli and Lactobacillus sp. For both S. aureus and P. aeruginosa, LSL achieved bacteriostatic and bactericidal effects by destroying the cell wall, increasing the permeability of the cell membrane and leading to the flow out of intracellular contents. However, the action mode and action intensity of LSL on the cell wall and membrane of these two bacteria were significantly different. LSL had a greater influence on the cell membrane of S. aureus by “leaking,” while it exhibited a stronger effect on the cell wall of P. aeruginosa by “blasting.” These results contributed to a better understanding of the relationship between LSL and different bacterial cell structures, further suggesting the conclusion that LSL might be used for the targeted treatment of special pathogenic bacteria.

Postmilking teat dip is an important tool used to prevent mastitis in the modern dairy industry. In this study, we evaluated the in vitro and in vivo efficacies of a barrier teat dip containing povidone-iodine and chitosan for the prevention of mastitis. In experiment 1, we evaluated the antibacterial effects of chitosans with different molecular weights against six mastitis-causing bacteria based on the minimal inhibitory concentration test. The results showed that 50 kDa chitosan had the maximum antibacterial activity compared with 5, 150 and 350 kDa chitosans. In experiment 2, the inhibition zone test indicated that the barrier teat dip with 4.0% povidone-iodine and 1.0% chitosan had higher (P0.05) in SCC, somatic cell score (SCS) or other milk quality indicators were observed between nonbarrier and barrier teat dip treatment teats throughout the experiment. At the end of experiment 4, compared with nonbarrier teat dip group, a reduction (P0.05) in milk qualities or clinical mastitis incidence were detected between groups. Bacteriological analysis demonstrated that the barrier product containing povidone-iodine and chitosan reduced the subclinical mastitis infection prevalence induced by mastitis pathogens. This effect was mainly due to the reductions in Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia fergusonii infections. Overall, the data indicated that a barrier teat dip containing 4% povidone-iodine and 1% chitosan was more effective than 10% povidone-iodine in preventing subclinical mastitis.

Cytochrome P450 genes are involved in the catalysis of various reactions, including growth, development and secondary metabolite biosynthetic pathways. However, little is known about the characteristics and functions of the P450 gene family in Chinese cabbage (Brassica rapa L. ssp. pekinensis). In this study, we identified 258 non-redundant members of the cytochrome P450 gene superfamily in Brassica. rapa from Brassica database (http://www.brassicadb.cn). We also did transcriptomic data mining derived from abiotic/biotic stresses and developmental related RNA-seq in Chinese cabbage. These differentially expressed genes (DEGs) were involved in cadmium (Cd) detoxification, salinity tolerance, calcium signaling transduction and homeostasis, pathogen triggered immunity and leafy head formation in Chinese cabbage. These P450 genes are essential candidates for a better understanding of the mechanism of P450 genes, which help Chinese cabbage adapt to environmental changes.

Introduction: Liddle syndrome (LS), an autosomal dominant and inherited monogenic hypertension syndrome caused by pathogenic mutations in the epithelial sodium channel (ENaC) genes SCNN1A, SCNN1B, and SCNN1G. Objective: This study was designed to identify a novel SCNN1B missense mutation in a Chinese family with a history of stroke, and to confirm that the identified mutation is responsible for LS in this family. Methods: DNA samples were collected from the proband and 11 additional relatives. Next-generation sequencing was performed in the proband to find candidate variants. In order to exclude genetic polymorphism, the candidate variantin SCNN1B was verified in other family members, 100 hypertensives, and 100 healthy controls by Sanger sequencing. Results: Genetic testing revealeda novel and rare heterozygous variant in SCNN1B in the proband. This variant resulted in a substitution of threonine instead of proline at codon 617, altering the PY motif of β-ENaC. The identified mutation was only verified in 5 relatives. In silico analyses indicated that this variant was highly pathogenic. In this family, phenotypic heterogeneity was present among 6 LS patients. Tailored medicine with amiloride was effective in controlling hypertension and improving the serum potassium concentration in patients with LS. Conclusions:We identified a novel SCNN1B mutation (c.1849C>A) in a family affected by LS. Patients with LS, especially those with severe hypertension, should be alert for the occurrence of premature stroke. Timely diagnosis using genetic testing and tailored treatment with amiloride can help LS patients to avoid severe complications.

Purpose: miR-5100 participates in the proliferation of lung cancer and pancreatic cancer cells, and participates in the differentiation of osteoblasts. However, the regulation of gastric cancer cells in gastric cancer cells remains unclear. Experimental design: The blood of patients was collected to detect the expression level of miR-5100, and the apoptosis and autophagy levels of cells were detected using western blot, flow cytometry, and confocal. At the same time, in vitro tumor formation experiments in nude mice were used to verify the results of in vitro experiments. Results: The expression of miR-5100 is related to the prognosis of gastric cancer, miR-5100 can enhance the apoptosis level of gastric cancer cells and inhibit the occurrence of autophagy by targeting CAAP1. MKL1 can inhibit the apoptosis of gastric cancer cells and promote the occurrence of autophagy by targeting CAAP1. At the same time, MKL1 can also increase the expression of miR-5100. Conclusions: Our research reveals the mechanism by which the MKL1/miR-5100/CAAP1 loop regulates apoptosis and autophagy levels in gastric cancer cells, and miR-5100 is expected to become a new potential target for gastric cancer treatment. Keywords: MKL1, miR-5100, CAAP1, Autophagy, Apoptosis, Gastric cancer

Soil productivity (SP) without external fertilization influence is an important indicator for the capacity of a soil to support crop yield. However, there have been difficulties in estimating values of SPs for soils after various long-term field treatments because the treatment without external fertilization is used but is depleted in soil nutrients, leading to erroneous estimation. The objectives of this study were to estimate the change of SP across different cropping seasons using pot experiments, and to evaluate the steady SP value (which is defined by the basal contribution of soil itself to crop yield) after various long-term fertilization treatments in soils at different geographical locations. The pot experiments were conducted in Jinxian of Jiangxi Province with paddy soil, Zhengzhou of Henan Province with fluvo-aquic soil, and Gongzhuling of Jilin Province with black soils, China. Soils were collected after long-term field fertilization treatments of no fertilizer (control; CK-F), chemical fertilizer (NPK-F), and combined chemical fertilizer with manure (NPKM-F). The soils received either no fertilizer (F0) or chemical fertilizer (F1) for 3–6 cropping seasons in pots, which include CK-P (control; no fertilizer from long-term field experiments for pot experiments), NPK-P (chemical fertilizer from long-term field experiments for pot experiments), and NPKM-P (combined chemical and organic fertilizers from long-term field experiments for pot experiments). The yield data were used to calculate SP values. The initial SP values were high, but decreased rapidly until a relatively steady SP was achieved at or after about three cropping seasons for paddy and fluvo-aquic soils. The steady SP values in the third cropping season from CK-P, NPK-P, and NPKM-P treatments were 37.7, 44.1, and 50.0% in the paddy soil, 34.2, 38.1, and 50.0% in the fluvo-aquic soil, with the highest value observed in the NPKM-P treatment for all soils. However, further research is required in the black soils to incorporate more than three cropping seasons. The partial least squares path mode (PLS-PM) showed that total N (nitrogen) and C/N ratio (the ratio of soil organic carbon and total N) had positive effects on the steady SP for all three soils. These findings confirm the significance of the incorporation of manure for attaining high soil productivity. Regulation of the soil C/N ratio was the other main factor for steady SP through fertilization management.

Thyroid cancer remains the most common endocrine malignancy worldwide, and its incidence has steadily increased over the past four years. Papillary Thyroid Cancer (PTC) is the most common differentiated thyroid cancer, accounting for 80–85% of all thyroid cancers. Mitochondrial proteins (MRPs) are an important part of the structural and functional integrity of the mitochondrial ribosomal complex. It has been reported that MRPL9 is highly expressed in liver cancer and promotes cell proliferation and migration, but it has not been reported in PTC. In the present study we found that MRPL9 was highly expressed in PTC tissues and cell lines, and lentivirus-mediated overexpression of MRPL9 promoted the proliferation and migration ability of PTC cells, whereas knockdown of MRPL9 had the opposite effect. The interaction between MRPL9 and GGCT (γ-glutamylcyclotransferase) was found by immunofluorescence and co-immunoprecipitation experiments (Co-IP). In addition, GGCT is highly expressed in PTC tissues and cell lines, and knockdown of GGCT/MRPL9 in vivo inhibited the growth of subcutaneous xenografts in nude mice and inhibited the formation of lung metastases. Mechanistically, we found that knockdown of GGCT/MRPL9 inhibited the MAPK/ERK signaling pathway. In conclusion, our study found that the interaction of GGCT and MRPL9 modulates the MAPK/ERK pathway, affecting the proliferation and migration of PTC cells. Therefore, GGCT/MRPL9 may serve as a potential biomarker for PTC monitoring and PTC treatment.

Gastric cancer (GC) is the fifth most common cancer and the third deadliest cancer in the world, and the occurrence and development of GC are influenced by epigenetics. Methyltransferase-like 3 (METTL3) is a prominent RNA n6-adenosine methyltransferase (m6A) that plays an important role in tumor growth by controlling the work of RNA. This study aimed to reveal the biological function and molecular mechanism of METTL3 in GC. The expression level of METTL3 in GC tissues and cells was detected by qPCR, Western blot and immunohistochemistry, and the expression level and prognosis of METTL3 were predicted in public databases. CCK-8, colony formation, transwell and wound healing assays were used to study the effect of METTL3 on GC cell proliferation and migration. In addition, the enrichment effect of METTL3 on DEK mRNA was detected by the RIP experiment, the m6A modification effect of METTL3 on DEK was verified by the MeRIP experiment and the mRNA half-life of DEK when METTL3 was overexpressed was detected. The dot blot assay detects m6A modification at the mRNA level. The effect of METTL3 on cell migration ability in vivo was examined by tail vein injection of luciferase-labeled cells. The experimental results showed that METTL3 was highly expressed in GC tissues and cells, and the high expression of METTL3 was associated with a poor prognosis. In addition, the m6A modification level of mRNA was higher in GC tissues and GC cell lines. Overexpression of METTL3 in MGC80-3 cells and AGS promoted cell proliferation and migration, while the knockdown of METTL3 inhibited cell proliferation and migration. The results of in vitro rescue experiments showed that the knockdown of DEK reversed the promoting effects of METTL3 on cell proliferation and migration. In vivo experiments showed that the knockdown of DEK reversed the increase in lung metastases caused by the overexpression of METTL3 in mice. Mechanistically, the results of the RIP experiment showed that METTL3 could enrich DEK mRNA, and the results of the MePIP and RNA half-life experiments indicated that METTL3 binds to the 3’UTR of DEK, participates in the m6A modification of DEK and promotes the stability of DEK mRNA. Ultimately, we concluded that METTL3 promotes GC cell proliferation and migration by stabilizing DEK mRNA expression. Therefore, METTL3 is a potential biomarker for GC prognosis and a therapeutic target.

Abstract Background Breast cancer is the leading cause of cancer death in women worldwide which is closely related to metastasis. But the exact molecular mechanism of ERα-36 and STAT3 on metastasis is still not fully understood. Methods MCF-7 and MDA-MB-231 human breast cancer cell lines and MCF-10A were overexpressioned or knockdown ERα-36 and STAT3 and tested for migration, invasion and proliferation assays. Direct interaction of STAT3 and ERα-36 were analyzed by coimmunoprecipitation assays. The effect of STAT3 and ERα-36 on MMP2/9 expression was analyzed by qPCR and western blotting. STAT3 phospholyation and acetylation by ERα-36 and p300 were observed and quantified by coimmunoprecipitation assays and western blotting. Results Cross-talk between ERα-36 and STAT3 was demonstrated to mediate through a direct physical association between the two proteins. Furthermore, the interaction between ERα-36 and STAT3 was demonstrated to give rise to functional changes in their signaling events. Both MMP2 and MMP9 expression require the binding of the newly identified protein complex, ERα-36-STAT3, to its promoter, the second phase, which is more robust, depends on ERα-mediated recruitment of p300 onto the complex and the subsequent acetylation of STAT3. In addition, STAT3 is tyrosine-phosphorylated in a biphasic manner, and the late phase requires ERα-36-mediated p300-dependent acetylation. Furthermore, interference with acetylation of STAT3 by overexpression of acetylation null STAT3 mutant led to the loss of MMP2 and MMP9 expression. ChIP analysis and reporter gene assays revealed that ERα-36-STAT3 complex binding to the MMP2 and MMP9 promoter led to an enhanceosome formation and facilitated MMP2 and MMP9 expression. Conclusions Our studies demonstrate for the first time that the function of MMP2 and MMP9 in breast cancer cell migration, which is mediated by interactions between ERα-36 and STAT3.

Background/Aims: Liddle syndrome (LS) is a rare autosomal dominant disease caused by mutations in genes coding for epithelial sodium channel (ENaC) subunits. The aim of this study was to identify the mutation responsible for the LS in an extended Chinese family. Methods: DNA samples from the proband with early-onset, treatment-resistant hypertension, and hypokalemia and 19 additional relatives were all sequenced for mutations in exon 13 of the β-ENaC and γ-ENaC genes, using amplification by polymerase chain reaction and direct DNA sequencing. Results: Genetic testing of exon 13 of SCNN1B revealed duplication of guanine into a string of 3 guanines located at codon 602. This frameshift mutation is predicted to generate a premature stop codon at position 607, resulting in truncated β-ENaC lacking the remaining 34 amino acids, including the crucial PY motif. Among a total of 9 participants with the identical mutation, different phenotypes were identified. Tailored treatment with amiloride was safe and effective in alleviating disease symptoms in LS. No mutation of SCNN1G was identified in any of the examined participants. Conclusions: We report here a family affected by LS harboring a frameshift mutation (c.1806dupG) with a premature stop codon deleting the PY motif of β-ENaC. Our study demonstrates that the earlier LS patients are diagnosed by genetic testing and treated with tailored medication, the greater the likelihood of preventing or minimizing complications in the vasculature and target organs.

There is limited information on carbon sequestration efficiency (CSE) of soil aggregates in upland and paddy soils under long-term fertilization regimes. In a red soil region of southern China, an upland soil experiment started in 1986 and a paddy soil experiment commenced in 1981. These experiments were conducted using different fertilization treatments. After 30 years, soil organic carbon (SOC) content and stock of different aggregate components were analyzed. The results showed that the SOC contents and stocks in upland soil were lower than in paddy soil. In both upland and paddy soils, the SOC contents and stocks of all aggregate components in NPKM (combined treatment with chemical nitrogen (N), phosphorus (P), potassium (K) fertilizers and manure) were the highest among all treatments. Compared with CK (no fertilizer), SOC content of all aggregate components in NPKM was increased by 13.21−63.11% and 19.13−73.33% in upland and paddy soils, respectively. Meanwhile, the change rates in SOC stock of all aggregate components in upland soil were lower than in paddy soil, although the change rate of SOC stock of all aggregate components in NPKM was higher than in other treatments. Furthermore, a linear equation could fit the relationships between carbon (C) input and change rate of SOC stock (P

Liddle syndrome (LS), a monogenetic autosomal dominant disorder, is mainly characterized by early-onset hypertension and hypokalemia. Clinically, misdiagnosis or missing diagnosis is common, since clinical phenotypes of LS are variable and nonspecific. We report a family with misdiagnosis of primary aldosteronism (PA), but identify as LS with a pathogenic frameshift mutation of the epithelial sodium channel (ENaC) β subunit. DNA samples were collected from a 32-year-old proband and 31 other relatives in the same family. A designed panel including 41 genes associated with monogenic hypertension was screened using next-generation sequencing. The best candidate disease-causing variants were verified by Sanger sequencing. Genetic analysis of the proband revealed a novel frameshift mutation c.1838delC (p.Pro613Glnfs*675) in exon 13 of SCNN1B. This heterozygous mutation involved the deletion of a cytosine from a string of three consecutive cytosines located at codons 612 to 613 and resulted in deletion of the crucial PY motif and elongation of the β-ENaC protein. The identical mutation was also found in 12 affected family members. Amiloride was effective in alleviating LS for patients. There were no SCNN1A or SCNN1G mutations in this family. Our study emphasizes the importance of considering LS in the differential diagnosis of early-onset hypertension. The identification of a novel frameshift mutation of SCNN1B enriches the genetic spectrum of LS and has allowed treatment of this affected family to prevent severe complications.

The macrophage-related immune response is an important component of the cochlear response to different exogenous stresses, including noise, ototoxic antibiotics, toxins, or viral infection. However, the role of the immune response in hereditary deafness caused by genetic mutations is rarely explored. GJB2, encoding connexin 26 (Cx26), is the most common deafness gene of hereditary deafness. In this study, two distinct Cx26-null mouse models were established to investigate the types and underlying mechanisms of immune responses. In a systemic Cx26-null model, macrophage recruitment was observed, associated with extensive cell degeneration of the cochlear epithelium. In a targeted-cell Cx26-null model, knockout of Cx26 was restricted to specific supporting cells (SCs), which led to preferential loss of local outer hair cells (OHCs). This local OHC loss can also induce a macrophage-related immune response. Common inflammatory factors, including TNF-α, IL-1β, Icam-1, Mif, Cx3cr1, Tlr4, Ccl2, and Ccr2, did not change significantly, while mRNA of Cx3cl1 was upregulated. Quantitative immunofluorescence showed that the protein expression of CX3CL1 in Deiters cells, a type of SC coupled with OHCs, increased significantly after OHC death. OHC loss caused the secondary death of spiral ganglion neurons (SGNs), while the remaining SGNs expressed high levels of CX3CL1 with infiltrated macrophages. Taken together, our results indicate that CX3CL1 signaling regulates macrophage recruitment and that enhancement of macrophage antigen-presenting function is associated with cell degeneration in Cx26-null mice.

Fc galactosylation is a critical quality attribute for anti-tumor recombinant immunoglobulin G (IgG)-based monoclonal antibody (mAb) therapeutics with complement-dependent cytotoxicity (CDC) as the mechanism of action. Although the correlation between galactosylation and CDC has been known, the underlying structure–function relationship is unclear. Heterogeneity of the Fc N-glycosylation produced by Chinese hamster ovary (CHO) cell culture biomanufacturing process leads to variable CDC potency. Here, we derived a kinetic model of galactose transfer reaction in the Golgi apparatus and used this model to determine the correlation between differently galactosylated species from CHO cell culture process. The model was validated by a retrospective data analysis of more than 800 historical samples from small-scale and large-scale CHO cell cultures. Furthermore, using various analytical technologies, we discovered the molecular basis for Fc glycan terminal galactosylation changing the three-dimensional conformation of the Fc, which facilitates the IgG1 hexamerization, thus enhancing C1q avidity and subsequent complement activation. Our study offers insight into the formation of galactosylated species, as well as a novel three-dimensional understanding of the structure–function relationship of terminal galactose to complement activation in mAb therapeutics.

Jervell and Lange-Nielsen syndrome (JLNS) is a rare but severe autosomal recessive disease characterized by profound congenital deafness and a prolonged QTc interval (greater than 500 milliseconds) in the ECG waveforms. The prevalence of JLNS is about 1/1000000 to 1/200000 around the world. However, exceed 25% of JLNS patients suffered sudden cardiac death with kinds of triggers containing anesthesia. Approximately 90% of JLNS cases are caused by KCNQ1 gene mutations. Here, using next-generation sequencing (NGS), we identified a compound heterozygosity for two mutations c.1741A>T (novel) and c.477+5G>A (known) in KCNQ1 gene as the possible pathogenic cause of JLNS, which suggested a high risk of cardiac events in a deaf child. The hearing of this patient improved significantly with the help of cochlear implantation (CI). But life-threatening arrhythmias occurred with a trigger of anesthesia after the end of the CI surgery. Our findings extend the KCNQ1 gene mutation spectrum and contribute to the management of deaf children diagnosed with JLNS for otolaryngologists (especially cochlear implant teams).

Waardenburg syndrome (WS), also known as auditory-pigmentary syndrome, is the most common cause of syndromic hearing loss. It is responsible for 2–5% of congenital deafness. WS is classified into four types depending on the clinical phenotypes. Currently, pathogenic mutation of PAX3, MITF, EDNRB, EDN3, SNAI2, or SOX10 can cause corresponding types of WS. Among them, SOX10 mutation is responsible for approximately 15% of type II WS or 50% of type IV WS. We report the case of a proband in a Chinese family who was diagnosed with WS type II. Whole exome sequencing (WES) of the proband detected a novel heterozygous spontaneous mutation: SOX10 c.246delC. According to analysis based on nucleic acid and amino acid sequences, this mutation may produce a truncated protein, with loss of the HMG structure domain. Therefore, this truncated protein may fail to activate the expression of the MITF gene, which regulates melanocytic development and plays a key role in WS. Our finding expands the database of SOX10 mutations associated with WS and provides more information regarding the molecular mechanism of WS.

Background: Liddle syndrome is an autosomal dominant form of monogenic hypertension. Phenotypic variability makes it difficult to identify patients with Liddle syndrome, resulting in misdiagnosis and severe complications at early age. Objectives: To identify mutation in SCNN1B and SCNN1G genes in an adolescent with suspicious Liddle syndrome and his family members and to explore the screening target subjects of Liddle syndrome. Methods: Genetic analysis of the C-terminus of SCNN1B and SCNN1G genes was conducted in an adolescent, with treatment-resistant hypertension and hypokalemia, who was suspected of having Liddle syndrome, and his family members. A Medline research of the reported cases with Liddle syndrome was also performed. Results: A recurrent SCNN1B mutation, c.1853C>A (p.P618H), was detected in the 19-year-old male patient, and family screening identified five additional members who were heterozygous for the mutation. The diagnosis of Liddle syndrome was made in all affected individuals. Despite the phenotypic variability, a systematic review of 54 reported index cases revealed the early-onset hypertension, aged no more than 30 years, as a common feature. Conclusions: Genetic screening for Liddle syndrome should be considered in hypertensive subjects with early penetrance, maybe no more than 30 years, after exclusion of common secondary causes of hypertension.

ISWI chromatin remodelers regulate DNA accessibility and have been implicated in DNA damage repair. Here, the authors uncover functions, in response to DNA damage, for the bromodomain of the ISWI subunit BAZ1B and for the non-canonical PHD and bromodomain modules of the paralog BAZ1A.

Auditory neuropathy spectrum disorder (ANSD), also called auditory neuropathy (AN), is a unique type of prelingual hearing impairment. Up to 10% of deaf infants and children are affected by this disease. Mutation of the OTOF gene which encodes otoferlin is the common cause of congenital nonsyndromic ANSD. To date, over 110 mutations have been identified in the OTOF gene according to the Human Gene Mutation Database (HGMD). Here, next-generation sequencing (NGS) revealed that the compound heterozygous mutations c.4748G>A/c.2523+1G>T and c.5248G>C/c.5098G>C of the OTOF gene were present in two Chinese ANSD patients. Each patient had a known pathogenic mutation (c.4748G>A or c.5098G>C) and a novel mutation (c.2523+1G>T or c.5248G>C). Comparative amino acid sequence analysis across different species revealed that the residues at these novel mutation sites are evolutionarily highly conservative. This indicated that the novel mutations were possible causes of the disorder in the patients. Our findings extend the OTOF mutation spectrum and further confirm the role of the OTOF gene in ANSD.

Background: Takayasu arteritis (TA) is a rare inflammatory arteriopathy of unknown etiology. The aim of this study was to investigate the genetic susceptibility to TA in a Chinese population. Methods: Four single nucleotide polymorphisms (SNPs) those locate in the IL12B region (rs56167332), the MLX region (rs665268), the FCGR2A/FCGR3A locus (rs10919543), and the HLA-B/MICA locus (rs12524487), associated with TA in different population, were genotyped in 123 Chinese TA patients and 147 healthy controls from January 2013 to August 2014. A Chi-square test was used to test for genotype/allele frequencies variants. Results: Among the four SNPs, rs10919543 was found to be significantly associated with TA in the studied population. The GG genotype of rs10919543 at the FCGR2A/FCGR3A locus is a high risk factor (odds ratio [OR] = 6.532, 95% confidence interval [CI] = 2.402 − 17.763, P < 0.001) for TA. Among TA patients, the level of eosinophil granulocytes (Eos) in the peripheral blood was observed to be higher in the GG group of rs10919543 (n = 23, Eos = 0.11 [0.08, 0.17] ×109/L) than the GA + AA group (n = 100, Eos = 0.08 [0.05, 0.13] ×109/L, P = 0.028). No correlation between the genotypes of the other three SNPs and TA patients was observed. Conclusions: Our findings revealed unique genetic pattern in Chinese TA patients that may be partly responsible for the higher risk of TA in this population. FCGR2A/FCGR3A-related immune disorder might contribute to the etiology of TA.

The improvement of soil productivity depends on a rational input of water and nutrients, optimal field management, and the increase of basic soil productivity (BSP). In this study, BSP is defined as the productive capacity of a farmland soil with its own physical and chemical properties for a specific crop season under local field management. Based on 19-yr data of the long-term agronomic experiments (1989–2008) on a fluvo-aquic soil in Zhengzhou, Henan Province, China, the decision support system for agrotechnology transfer (DSSAT ver. 4.0) crop growth model was used to simulate yields by BSP of winter wheat (Triticum aestivium L.) and summer maize (Zea mays L.) to examine the relationship between BSP and soil organic carbon (SOC) under long-term fertilization. Five treatments were included: (1) no fertilization (control), (2) nitrogen, phosphorus and potassium fertilizers (NPK), (3) NPK plus manure (NPKM), (4) 1.5 times of NPKM (1.5NPKM), and (5) NPK plus straw (NPKS). After 19 yr of treatments, the SOC stock increased 16.7, 44.2, 69.9, and 25.2% under the NPK, NPKM, 1.5NPKM, and NPKS, respectively, compared to the initial value. Among various nutrient factors affecting contribution percentage of BSP to winter wheat and summer maize, SOC was a major affecting factor for BSP in the fluvo-aquic soil. There were significant positive correlations between SOC stock and yields by BSP of winter wheat and summer maize (P

Silent information regulator protein 1(SIRT1)is one of the sirtuins and belongs to histone deacetyase. Its activity depends on nicotinamide adenine dinucleotide(NAD+)and is regulated by NAD+. Experimental and clinical studies have shown the neuro-protective effect of SIRT1 in the pathogenesis of age-related eye diseases. In this review, the relationship between SIRT1 activator and apoptosis in the retinal cells were discussed. The review also points to SIRT1 as a potential therapeutic target for the clinical management of age-related retinal disease.

Increasing basic farmland soil productivity has significance in reducing fertilizer application and maintaining high yield of crops. In this study, we defined that the basic soil productivity (BSP) is the production capacity of a farmland soil with its own physical and chemical properties for a specific crop season under local environment and field management. Based on 22-yr (1990–2011) long-term experimental data on black soil (Typic hapludoll) in Gongzhuling, Jilin Province, Northeast China, the decision support system for an agro-technology transfer (DSSAT)-CERES-Maize model was applied to simulate the yield by BSP of spring maize (Zea mays L.) to examine the effects of long-term fertilization on changes of BSP and explore the mechanisms of BSP increasing. Five treatments were examined: (1) no-fertilization control (control); (2) chemical nitrogen, phosphorus, and potassium (NPK); (3) NPK plus farmyard manure (NPKM); (4) 1.5 time of NPKM (1.5NPKM) and (5) NPK plus straw (NPKS). Results showed that after 22-yr fertilization, the yield by BSP of spring maize significantly increased 78.0, 101.2, and 69.4% under the NPKM, 1.5NPKM and NPKS, respectively, compared to the initial value (in 1992), but not significant under NPK (26.9% increase) and the control (8.9% decrease). The contribution percentage of BSP showed a significant rising trend (PNPKM>NPK≈NPKS, indicating that organic manure combined with chemical fertilizers (1.5NPKM and NPKM) could more effectively increase BSP compared with the inorganic fertilizer application alone (NPK) in the black soil. This study showed that soil organic matter (SOM) was the key factor among various fertility factors that could affect BSP in the black soil, and total N, total P and/or available P also played important role in BSP increasing. Compared with the chemical fertilization, a balanced chemical plus manure or straw fertilization (NPKM or NPKS) not only increased the concentrations of soil nutrient, but also improved the soil physical properties, and structure and diversity of soil microbial population, resulting in an iincrease of BSP. We recommend that a balanced chemical plus manure or straw fertilization (NPKM or NPKS) should be the fertilization practices to enhance spring maize yield and improve BSP in the black soil of Northeast China.

Soil organic carbon (SOC) and soil Olsen-P are key soil fertility indexes but information on their relationships is limited particularly under long-term fertilization. We investigated the relationships between SOC and the percentage of soil Olsen-P to total P (PSOPTP) under six different 15-yr (1990–2004) long-term fertilizations at two cropping systems in northern China. These fertilization treatments were (1) unfertilized control (control); (2) chemical nitrogen (N); (3) N plus chemical P (NP); (4) NP plus chemical potassium (NPK); (5) NPK plus animal manure (NPKM) and (6) high NPKM (hNPKM). Compared with their initial values in 1989 at both sites, during the 11th to 15th fertilization years annual mean SOC contents were significantly increased by 39.4–47.0% and 58.9–93.9% at Gongzhuling, Jilin Province, and Urumqi, Xinjiang, China, under the two NPKM fertilizations, respectively, while no significant changes under the no-P or chemical P fertilization. During the 11th to 15th fertilization years, annual mean PSOPTP was respectively increased by 2.6–4.2 and 5.8–14.1 times over the initial values under the two chemical P fertilizations and the two NPKM fertilizations, but was unchanged in their initial levels under the two no-P fertilizations at both sites. Over the 15-yr long-term fertilization SOC significantly positively correlated with PSOPTP (r2=0.55–0.79, P

Two new dimeric 1,4-benzoquinone derivatives, peniquinone A (1) and peniquinone B (2), a new dibenzofuran penizofuran A (3), and a new pyrazinoquinazoline derivative quinadoline D (4), together with 13 known compounds (5−17), were isolated from a marine-derived fungus Penicillium sp. L129. Their structures, including absolute configurations, were elucidated by extensive spectroscopic data and electronic circular dichroism calculations. Compound 1 exhibited cytotoxicity against the MCF-7, U87 and PC3 cell lines with IC50 values of 12.39 µM, 9.01 µM and 14.59 µM, respectively, while compound 2 displayed relatively weak cytotoxicity activities against MCF-7, U87 and PC3 cell lines with IC50 values of 25.32 µM, 13.45 µM and 19.93 µM, respectively. Furthermore, compound 2 showed weak quorum sensing inhibitory activity against Chromobacterium violaceum CV026 with an MIC value of 20 μg/well.

Long-term fertilization experiment provides the platform for understanding the proton budgets in nitrogen transformations of agricultural ecosystems. We analyzed the historical (1990–2005) observations on four agricultural long-term experiments in China (Changping, Chongqing, Gongzhuling and Qiyang) under four different fertilizations, i.e., no-fertilizer (control), sole chemical nitrogen fertilizer (FN), sole chemical phosphorous and potassium fertilizers (FPK) and chemical nitrogen, phosphorous and potassium fertilizers (FNPK). The significant decline in topsoil pH was caused not only by chemical N fertilization (0.29 and 0.89 ΔpH at Gongzhuling and Qiyang, respectively) but also by chemical PK fertilization (0.59 ΔpH at Gongzhuling). The enhancement of available nutrients in the topsoil due to long-term direct nutrients supply with chemical fertilizers was in the descending order of available P (168–599%)>available K (16–189%)>available N (9–33%). The relative rate of soil pH decline was lower under long-term judicious chemical fertilization (−0.036–0.034 ΔpH yr−1) than that under long-term sole N or PK fertilization (0.016–0.086 ΔpH yr−1). Long-term judicious chemical fertilization with N, P and K elements decreases the nutritional limitation to normal crop growth, under which more N output was distributed in biomass removal rather than the loss via nitrate leaching. We concluded that the N distribution percentage of nitrate leaching to biomass removal might be a suitable indicator to the sensitivity of agricultural ecosystems to acid inputs.

AIM: To examine choroidal thickness and its relationship with axial length and spherical equivalent by spectral domain optical coherence tomography(SD-OCT)in patients with myopic choroidal neovascularization(mCNV). METHODS: We prospectively recruited 30 cases of mCNV in Beijing Anzhen Hospital from October 2010 to December 2014. SD-OCT was used to measure choroidal thickness subfoveally and at 1.5mm superiorly, inferiorly, nasally and temporally(SFCT, SCT1.5mm, ICT1.5mm, NCT1.5mm, TCT1.5mm). Paired t-test was conducted to assess the difference of spherical equivalent, axial length and choroidal thickness between mCNV group and controls. Logistic regression analysis was performed to evaluate the correlation between spherical equivalent, axial length, choroidal thickness and mCNV. RESULTS: The difference of spherical equivalent and axial length between mCNV group and controls was not significant(P>0.05). Inferior was decreased in mCNV group compared with controls(140.85±33.46μm vs 168.95±45.36μm). The difference was significant(P=0.008). Logistic regression demonstrated that decreased choroidal thickness(ICT1.5mm)at inferior location was associated with mCNV(OR=2.12; 95%CI 1.35～3.28; P=0.02). CONCLUSION: The decrease of ICT1.5MM may be one of the risk factors of mCNV.

Thin-film ferroelectrics have been pursued for capacitive and nonvolatile memory devices. They rely on polarizations that are oriented in an out-of-plane direction to facilitate integration and addressability with complementary metal-oxide semiconductor architectures. The internal depolarization field, however, formed by surface charges can suppress the out-of-plane polarization in ultrathin ferroelectric films that could otherwise exhibit lower coercive fields and operate with lower power. Here, we unveil stabilization of a polar longitudinal optical (LO) mode in the n = 2 Ruddlesden-Popper family that produces out-of-plane ferroelectricity, persists under open-circuit boundary conditions, and is distinct from hyperferroelectricity. Our first-principles calculations show the stabilization of the LO mode is ubiquitous in chalcogenides and halides and relies on anharmonic trilinear mode coupling. We further show that the out-of-plane ferroelectricity can be predicted with a crystallographic tolerance factor, and we use these insights to design a room-temperature multiferroic with strong magnetoelectric coupling suitable for magneto-electric spin-orbit transistors. [ABSTRACT FROM AUTHOR]

We assessed the pharmacovigilance (PV), reporting rate, severity, and reaction outcomes of major adverse cardiovascular events (MACE) related to ARPI for prostate cancer reported to the United States Food and Drug Administration Adverse Event Reporting System (FAERS) between January 2014 and December 2022.Considering the MACE safety profile, enzalutamide may be a better choice for prostate cancer. This needs to be further confirmed by larger prospective studies and longer follow-up periods. Background: The potential cardiovascular adverse events associated with new-generation androgen receptor pathway inhibitors (ARPI) in the treatment of prostate cancer remain unclear. We aimed to assess the pharmacovigilance (PV), reporting rate, severity, and reaction outcomes of major adverse cardiovascular events (MACE) related to newgeneration ARPI for prostate cancer reported to the United States Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: We analyzed reports of cardiovascular adverse events associated with drug therapy for prostate cancer submitted to FAERS between January 2014 and December 2022. Three primary new-generation ARPIs were identified: abiraterone acetate, enzalutamide, and apalutamide. Our primary composite endpoint was the PV of MACE caused by ARPIs in the treatment of prostate cancer, and the secondary endpoint was PV of other cardiovascular events. The software implemented was STATA 17.0 MP. Results: A total of 278,031 suspected drug-adverse event pairs related to drug treatment in patients with prostate cancer were identified, of which 10,861 reports were cardiovascular events, including 5800 reports of MACE and 5061 reports of other cardiovascular events. The majority of these cardiovascular adverse event reports came from the United States (36.6%) and were mostly older men (age 76.0 ± 8.6 years). Compared with enzalutamide, the constituent ratio of MACE caused by abiraterone acetate and apalutamide was significantly increased, but the incidence of severe MACE decreased significantly. The PV signal regarding MACE was detected in abiraterone acetate and apalutamide but not in enzalutamide. Conclusion: Abiraterone acetate and apalutamide presumably are associated with a higher risk of MACE than enzalutamide in new-generation ARPI for prostate cancer. More extensive prospective studies and more extended follow-up periods need to confirm this further. [ABSTRACT FROM AUTHOR]