Giant modulation of optical nonlinearity by Floquet engineering.

Strong periodic driving with light offers the potential to coherently manipulate the properties of quantum materials on ultrafast timescales. Recently, strategies have emerged to drastically alter electronic and magnetic properties by optically inducing non-trivial band topologies1-6, emergent spin interactions7-11 and even superconductivity12. However, the prospects and methods of coherently engineering optical properties on demand are far less understood13. Here we demonstrate coherent control and giant modulation of optical nonlinearity in a van der Waals layered magnetic insulator, manganese phosphorus trisulfide (MnPS3). By driving far off-resonance from the lowest on-site manganese d-d transition, we observe a coherent on-off switching of its optical second harmonic generation efficiency on the timescale of 100 femtoseconds with no measurable dissipation. At driving electric fields of the order of 109 volts per metre, the on-off ratio exceeds 10, which is limited only by the sample damage threshold. Floquet theory calculations14 based on a single-ion model of MnPS3 are able to reproduce the measured driving field amplitude and polarization dependence of the effect. Our approach can be applied to a broad range of insulating materials and could lead to dynamically designed nonlinear optical elements.

Electrostatic Gating of Spin Dynamics of a Quasi-2D Kagome Magnet.

Electrostatic gating has emerged as a powerful technique for tailoring the magnetic properties of two-dimensional (2D) magnets, offering exciting prospects including enhancement of magnetic anisotropy, boosting Curie temperature, and strengthening exchange coupling effects. Here, we focus on electrical control of the ferromagnetic resonance of the quasi-2D Kagome magnet Cu(1,3-bdc). By harnessing an electrostatic field through ionic liquid gating, significant shifts are observed in the ferromagnetic resonance field in both out-of-plane and in-plane measurements. Moreover, the effective magnetization and gyromagnetic ratios display voltage-dependent variations. A closer examination reveals that the voltage-induced changes can modulate magnetocrystalline anisotropy by several hundred gauss, while the impact on orbital magnetization remains relatively subtle. Density functional theory (DFT) calculations reveal varying d-orbital hybridizations at different voltages. This research unveils intricate physics within the Kagome lattice magnet and further underscores the potential of electrostatic manipulation in steering magnetism with promising implications for the development of spintronic devices.

Pemigatinib, a selective FGFR inhibitor overcomes ABCB1-mediated multidrug resistance in cancer cells.

P: -glycoprotein (P-gp/ABCB1) overexpression is one of the primary causes of multidrug resistance (MDR). Therefore, it is crucial to discover effective pharmaceuticals to combat multidrug resistance mediated by ABCB1. Pemigatinib is a selective the fibroblast growth factor receptor (FGFR) inhibitor that is used to treat a variety of solid tumors, Clinical Trials for Urothelial Carcinoma (NCT02872714) completed its research on Pemigatinib. This study aimed to determine whether Pemigatinib can reverse ABCB1-mediated multidrug resistance, as well as its mechanism of action. Pemigatinib substantially reversed ABCB1-mediated multidrug resistance, as determined by a CCK8 assay, and immunofluorescence experiments revealed that Pemigatinib had no effect on the intracellular localization of ABCB1. Pemigatinib was discovered to increase intracellular drug accumulation, thereby reversing multidrug resistance. In addition, Docking analysis revealed that Pemigatinib and ABCB1 have a high affinity for one another. This study concludes that Pemigatinib is capable of reversing the multidrug resistance mediated by ABCB1, offering ideas and references for the clinical application of Pemigatinib.

Auranofin inhibits the occurrence of colorectal cancer by promoting mTOR-dependent autophagy and inhibiting epithelial-mesenchymal transformation.

Colorectal cancer (CRC) is one of the world's most common and deadly cancers. According to GLOBOCAN2020's global incidence rate and mortality estimates, CRC is the third main cause of cancer and the second leading cause of cancer-related deaths worldwide. The US Food and Drug Administration has approved auranofin for the treatment of rheumatoid arthritis. It is a gold-containing chemical that inhibits thioredoxin reductase. Auranofin has a number of biological activities, including anticancer activity, although it has not been researched extensively in CRC, and the mechanism of action on CRC cells is still unknown. The goal of this research was to see how Auranofin affected CRC cells in vivo and in vitro . The two chemical libraries were tested for drugs that make CRC cells more responsive. The CCK-8 technique was used to determine the cell survival rate. The invasion, migration, and proliferation of cells were assessed using a transwell test and a colony cloning experiment. An electron microscope was used to observe autophagosome formation. Western blotting was also used to determine the degree of expression of related proteins in cells. Auranofin's tumor-suppressing properties were further tested in a xenograft tumor model of human SW620 CRC cells. Auranofin dramatically reduced the occurrence of CRC by decreasing the proliferation, migration, and invasion of CRC cells, according to our findings. Through a mTOR-dependent mechanism, auranofin inhibits the epithelial-mesenchymal transition (EMT) and induces autophagy in CRC cells. Finally, in-vivo tests revealed that auranofin suppressed tumor growth in xenograft mice while causing no harm. In summary, auranofin suppresses CRC cell growth, invasion, and migration. Auranofin inhibits the occurrence and progression of CRC by decreasing EMT and inducing autophagy in CRC cells via a mTOR-dependent mechanism. These findings suggest that auranofin could be a potential chemotherapeutic medication for the treatment of human CRC.

Coping with groundwater pollution in high-nitrate leaching areas: The efficacy of denitrification.

The Ningxia Yellow River irrigation area, characterized by an arid climate and high leaching of NO3--N, exhibits complex and unique groundwater nitrate (NO3--N) pollution, with denitrification serving as the principal mechanism for NO3--N removal. The characteristics of N leaching from paddy fields and NO3--N removal by groundwater denitrification were investigated through a two-year field observation. The leaching losses of total nitrogen (TN) and NO3--N accounted for 10.81-27.34% and 7.59-12.74%, respectively, of the N input. The linear relationship between NO3--N leaching and N input indicated that the fertilizer-induced emission factor (EF) of NO3--N leaching in direct dry seeding and seedling-raising and transplanting paddy fields was 8.2% (2021, R2 = 0.992) and 6.7% (2022, R2 = 0.994), respectively. The study highlighted that the quadratic relationship between the NO3--N leaching loss and N input (R2 = 0.999) significantly outperformed the linear relationship. Groundwater denitrification capacity was characterized by monitoring the concentrations of dinitrogen (N2) and nitrous oxide (N2O). The results revealed substantial seasonal fluctuations in excess N2 and N2O concentrations in groundwater, particularly following fertilization and irrigation events. The removal efficiency of NO3--N via groundwater denitrification ranged from 42.70% to 74.38%, varying with depth. Groundwater denitrification capacity appeared to be linked to dissolved organic carbon (DOC) concentration, redox conditions, fertilization, irrigation, and soil texture. The anthropogenic-alluvial soil with limited water retention accelerated the leaching of NO3--N into groundwater during irrigation. This process enhances the groundwater recharge capacity and alters the redox conditions of groundwater, consequently impacting groundwater denitrification activity. The DOC concentration emerged as the primary constraint on the groundwater denitrification capacity in this region. Hence, increasing carbon source concentration and enhancing soil water retention capacity are vital for improving the groundwater denitrification capacity and NO3--N removal efficiency. This study provides practical insights for managing groundwater NO3--N pollution in agricultural areas, optimizing fertilization strategies and improving groundwater quality.

Fatigue and sleep quality in Chinese adults with connective tissue disease: A cross-sectional study.

OBJECTIVES: This study aims to evaluate fatigue and sleep quality among adults with connective tissue disease (CTD), and the interrelationship. METHODS: From April 2020 to February 2021, adult CTD patients hospitalized were invited to complete sociodemographic and disease-related data, Fatigue Severity Scale (FSS), and Pittsburgh Sleep Quality Index (PSQI), as well as laboratory detection through computer query. Statistical analysis was performed using SPSS 22.0. RESULTS: A total of 363 patients with CTD were included in the study. Of which, 313 patients were accompanied by single CTD (systemic lupus erythematosus (SLE) = 109, Sjogren's syndrome (SS) = 51, rheumatoid arthritis (RA) = 44, idiopathic inflammatory myopathies (IIM) = 36, Vasculitis = 17, systemic sclerosis (SSc) = 14, other = 42, respectively), and 50 patients had CTD ≥ 2. Compared with CTD = 1, patients with CTD ≥ 2 had longer disease duration, higher erythrocyte sedimentation rate, and higher IgG level (all P < 0.05). The prevalence of poor sleep quality in 363 CTD patients was 61.2%, among which, 59.1% for CTD = 1 and 74.0% for CTD ≥ 2, with significant difference (P = 0.045). Additionally, 75.5% experienced fatigue, and 75.4% for CTD = 1, 76.0% for CTD ≥ 2 (P = 0.927). Fatigue and sleep quality interacted in CTD patients (r = 0.236, P < 0.01; χ2 = 11.302, P = 0.001). Interestingly, no significant differences were found in the prevalence of fatigue and poor sleep quality among CTD subgroups, as well as the FSS score, the seven components of sleep quality and total PSQI score (P > 0.05). CONCLUSIONS: More than 3/5 CTD patients experience fatigue and poor sleep quality, and not different among CTD subgroups. Targeted interventions are needed to reduce fatigue, improve sleep quality, and ultimately improve the prognosis of patients with CTD.

ERECTA1 Acts Upstream of the OsMKKK10-OsMKK4-OsMPK6 Cascade to Control Spikelet Number by Regulating Cytokinin Metabolism in Rice.

Grain number is a flexible trait that strongly contributes to grain yield. In rice (Oryza sativa), the OsMKKK10-OsMKK4-OsMPK6 cascade, which is negatively regulated by the dual-specificity phosphatase GSN1, coordinates the trade-off between grain number and grain size. However, the specific components upstream and downstream of the GSN1-MAPK module that regulate spikelet number per panicle remain obscure. Here, we report that ERECTA1 (OsER1), a negative regulator of spikelet number per panicle, acts upstream of the OsMKKK10-OsMKK4-OsMPK6 cascade and that the OsER1-OsMKKK10-OsMKK4-OsMPK6 pathway is required to maintain cytokinin homeostasis. OsMPK6 directly interacts with and phosphorylates the zinc finger transcription factor DST to enhance its transcriptional activation of CYTOKININ OXIDASE2 (OsCKX2), indicating that the OsER1-OsMKKK10-OsMKK4-OsMPK6 pathway shapes panicle morphology by regulating cytokinin metabolism. Furthermore, overexpression of either DST or OsCKX2 rescued the spikelet number phenotype of the oser1, osmkkk10, osmkk4, and osmpk6 mutants, suggesting that the DST-OsCKX2 module genetically functions downstream of the OsER1-OsMKKK10-OsMKK4-OsMPK6 pathway. These findings reveal specific crosstalk between a MAPK signaling pathway and cytokinin metabolism, shedding light on how developmental signals modulate phytohormone homeostasis to shape the inflorescence.

[Structural characterization of PCP-â from Poria as vaccine adjuvant and its hydrolytic oligosaccharide].

Poria is an important medical herb in clinic. The authors isolated a polysaccharide(PCP-Ⅰ) from Poria in previous studies, which is composed of galactose, mannose, fucose and glucose. PCP-Ⅰ exhibited significant adjuvant effects on H1N1 influenza vaccine, hepatitis B surface antigen and anthrax protective antigen, and its adjuvant activity was stronger than aluminium adjuvant. However, little is known about the chemical structure of PCP-Ⅰ at present. In this study, weak acid hydrolysis was used to obtain the backbone oligosaccharide of PCP-Ⅰ. Then periodate oxidation, Smith degradation, methylation analysis, Fourier transform infrared spectroscopy(FT-IR), nuclear magnetic resonance(NMR) and gas chromatography-mass spectrometry(GC-MS) were performed to investigate the chemical structural features of PCP-Ⅰ and its hydrolytic oligosaccharide(PCP-Ⅰ-hy-1). These results suggested that the backbone of PCP-Ⅰ was composed of galactose with α anomeric carbon and ß anomeric carbon. The linking residues of galactan are(1→),(l→6) and(1→2,6).

Clinical value of contrast-enhanced ultrasound enhancement patterns for differentiating solid pancreatic lesions.

OBJECTIVES: To explore the diagnostic value of contrast-enhanced ultrasound (CEUS) enhancement patterns for differentiating solid pancreatic lesions and compare them with conventional ultrasound (US) and enhanced computed tomography (CT). METHODS: A total of 210 patients with solid pancreatic lesions who had definite pathological or clinical diagnoses were enrolled. Six CEUS enhancement patterns were proposed for solid pancreatic lesions. Two US doctors blindly observed the CEUS patterns of solid pancreatic lesions and the interrater agreement was analyzed. The diagnostic value of CEUS enhancement patterns for differentiating solid pancreatic lesions was evaluated, and the diagnostic accuracy was compared with that of US and enhanced CT. RESULTS: There was good concordance for six CEUS enhancement patterns of solid pancreatic lesions between the two doctors, with a kappa value of 0.767. Hypo-enhancement (Hypo-E) or centripetal enhancement (Centri-E) as the diagnostic criteria for pancreatic carcinoma had an accuracy of 87.62%; hyper-enhancement (Hyper-E) for neuroendocrine tumors had an accuracy of 92.89%; capsular enhancement with low or uneven enhancement inside the tumor (Capsular-E) for solid pseudopapillary tumors had an accuracy of 97.63%; and iso-enhancement (Iso-E) or iso-enhancement with focal hypo-enhancement (Iso-fhypo-E) for focal pancreatitis had an accuracy of 89.10%. The diagnostic accuracy of CEUS was significantly different from that of US for 210 cases of solid pancreatic lesions (p < 0.05) and was not significantly different from that of enhanced CT for 146 cases of solid pancreatic lesions (p > 0.05). CONCLUSIONS: The different enhancement patterns of solid pancreatic lesions on CEUS were clinically valuable for differentiation. KEY POINTS: • Six CEUS enhancement (E) patterns, including Hyper-E, Iso-E, Iso-fhypo-E, Hypo-E, Centri-E, and Capsular-E, are proposed for the characterization of solid pancreatic lesions. • Using Hypo-E or Centri-E as the diagnostic criteria for pancreatic carcinoma, Hyper-E for neuroendocrine tumors, Capsular-E for solid pseudopapillary tumors, and Iso-E or Iso-fhypo-E for focal pancreatitis on CEUS had relatively high diagnostic accuracy. • The diagnostic accuracy of CEUS was greatly increased over that of US and was not different from that of enhanced CT.

Conversion from rice fields to vegetable fields alters product stoichiometry of denitrification and increases N2O emission.

Information about effects of conversion from rice fields to vegetable fields on denitrification process is still limited. In this study, denitrification rate and product ratio (i.e., N2O/(N2O + N2) ratio) were investigated by soil-core incubation based N2/Ar technique in one rice paddy field (RP) and two vegetable fields (VF4 and VF7, 4 and 7 years vegetable cultivating after conversion from rice fields, respectively). Genes related to denitrification and bacterial community composition were quantified to investigate the microbial mechanisms behind the effects of land-use conversion. The results showed that conversion of rice fields to vegetable fields did not significantly change denitrification rate although the abundance of denitrification related genes was significantly reduced by 79.22%-99.84% in the vegetable soils. Whereas, compared with the RP soil, N2O emission rate was significantly (P < 0.05) increased by 53.5 and 1.6 times in the VF4 and VF7 soils, respectively. Correspondingly, the N2O/(N2O + N2) ratio increased from 0.18% (RP soil) to 5.65% and 0.65% in the VF4 and VF7 soils, respectively. These changes were mainly attributed to the lower pH, higher nitrate content, and the altered bacterial community composition in the vegetable soils. Overall, our results showed that conversion of rice fields to vegetable fields increased the N2O emission rate and altered the product ratio of denitrification. This may increase the contribution of land-use conversion to global warming and stratospheric ozone depletion.

Multimodal imaging of the course of retinal changes in acute posterior multifocal placoid pigment epitheliopathy with bilateral retinal detachment: a case report.

BACKGROUND: To report a rare case of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) with a combination of serous retinal detachment, papilledema, and retinal vasculitis. CASE PRESENTATION: A 19-year-old male complained of floaters in both eyes with decreased vision for 4 days. The best corrected visual acuity of the right eye and the left eye were 1.1 and 0.9 (logMAR), respectively. In both eyes, inflammatory cells can be seen suspended within the vitreous, multiple yellow/white lesions can be seen near the macula, and retinal neuroepithelial detachment. Swelling of the optic disc with blurring of the disc margins, in the left eye. Optical coherence tomography (OCT): showed retinal detachment in both eyes. The patient received oral prednisone treatment. 1 week later, OCT showed absorption of subretinal fluid in the macula of both eyes his binocular vision improved to 0.1 (logMAR). During the subsequent 28-month follow-up, fundus fluorescein angiography and OCT revealed extensive and progressive pigment epithelial atrophy in both eyes, and abnormal retinal vascular perfusion in the right eye due to persistent retinal vasculitis. Although the patient's binocular visual acuity remained at 0.1 (logMAR). CONCLUSIONS: In the present case of APMPPE with a combination of serous retinal detachment, papilledema, and retinal vasculitis, through the multimodal imaging, further confirming that the lesions were located in the choroid, while the pigment epithelial lesions were secondary changes.

Machine Learning Assisted Doppler Features for Enhancing Thyroid Cancer Diagnosis: A Multi-Cohort Study.

BACKGROUND: This pilot study aims at exploiting machine learning techniques to extract color Doppler ultrasound (CDUS) features and to build an artificial neural network (ANN) model based on these CDUS features for improving the diagnostic performance of thyroid cancer classification. METHODS: A total of 674 patients with 712 thyroid nodules (TNs) (512 from internal dataset and 200 from external dataset) were randomly selected in this retrospective study. We used ANN to build a model (TDUS-Net) for classifying malignant and benign TNs using both the automatically extracted quantitative CDUS features (whole ratio, intranodular ratio, peripheral ratio, and number of vessels) and gray-scale ultrasound (US) features defined by the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS). Then, we compared the diagnostic performance of the model, the performance of another ANN model based on the gray-scale US features alone (TUS-Net), and that of radiologists. RESULTS: The TDUS-Net (0.898, 95% CI: 0.868-0.922) achieved a higher area under the curve (AUC) than that of TUS-Net (0.881, 95% CI: 0.850-0.908) in the internal tests. Compared with radiologists, TDUS-Net (AUC: 0.925, 95% CI: 0.880-0.958) performed better than radiologists (AUC: 0.810, 95% CI: 0.749-0.862) in the external tests. CONCLUSIONS: Applying a machine learning model by combining both gray-scale US features and CDUS features can achieve comparable or even higher performance than radiologists in classifying TNs.

A quantitative trait locus GW6 controls rice grain size and yield through the gibberellin pathway.

Grain size is one of the essential components determining rice yield and is a target for both domestication and artificial breeding. Gibberellins (GAs) are diterpenoid phytohormones that influence diverse aspects of plant growth and development. Several quantitative trait loci (QTLs) have been identified that control grain size through phytohormone regulation. However, little is known about the role of GAs in the control of grain size. Here we report the cloning and characterization of a QTL, GW6 (GRAIN WIDTH 6), which encodes a GA-regulated GAST family protein and positively regulates grain width and weight. GW6 is highly expressed in the young panicle and increases grain width by promoting cell expansion in the spikelet hull. Knockout of GW6 exhibits reduced grain size and weight, whereas overexpression of GW6 results in increased grain size and weight. GW6 is induced by GA and its knockout downregulates the expression of GA biosynthesis genes and decreases GA content in the young panicle. We found that a natural variation in the cis element CAAT-box in the promoter of GW6 is associated with its expression level and grain width and weight. Furthermore, introduction of GW6 to Oryza indica variety HJX74 can lead to a 10.44% increase in rice grain yield, indicating that GW6 has great potential to improve grain yield in rice.

A SAC Phosphoinositide Phosphatase Controls Rice Development via Hydrolyzing PI4P and PI(4,5)P2.

Phosphoinositides (PIs) as regulatory membrane lipids play essential roles in multiple cellular processes. Although the exact molecular targets of PI-dependent modulation remain largely elusive, the effects of disturbed PI metabolism could be employed to identify regulatory modules associated with particular downstream targets of PIs. Here, we identified the role of GRAIN NUMBER AND PLANT HEIGHT1 (GH1), which encodes a suppressor of actin (SAC) domain-containing phosphatase with unknown function in rice (Oryza sativa). Endoplasmic reticulum-localized GH1 specifically dephosphorylated and hydrolyzed phosphatidylinositol 4-phosphate (PI4P) and phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. Inactivation of GH1 resulted in massive accumulation of both PI4P and PI(4,5)P2, while excessive GH1 caused their depletion. Notably, superabundant PI4P and PI(4,5)P2 could both disrupt actin cytoskeleton organization and suppress cell elongation. Interestingly, both PI4P and PI(4,5)P2 inhibited actin-related protein2 and -3 (Arp2/3) complex-nucleated actin-branching networks in vitro, whereas PI(4,5)P2 showed more dramatic effects in a dose-dependent manner. Overall, the overaccumulation of PI(4,5)P2 resulting from dysfunction of SAC phosphatase possibly perturbs Arp2/3 complex-mediated actin polymerization, thereby disordering cell development. These findings imply that the Arp2/3 complex might be the potential molecular target of PI(4,5)P2-dependent modulation in eukaryotes, thereby providing insights into the relationship between PI homeostasis and plant growth and development.

GRAIN SIZE AND NUMBER1 Negatively Regulates the OsMKKK10-OsMKK4-OsMPK6 Cascade to Coordinate the Trade-off between Grain Number per Panicle and Grain Size in Rice.

Grain number and size are interactive agronomic traits that determine grain yield. However, the molecular mechanisms responsible for coordinating the trade-off between these traits remain elusive. Here, we characterized the rice (Oryza sativa) grain size and number1 (gsn1) mutant, which has larger grains but sparser panicles than the wild type due to disordered localized cell differentiation and proliferation. GSN1 encodes the mitogen-activated protein kinase phosphatase OsMKP1, a dual-specificity phosphatase of unknown function. Reduced expression of GSN1 resulted in larger and fewer grains, whereas increased expression resulted in more grains but reduced grain size. GSN1 directly interacts with and inactivates the mitogen-activated protein kinase OsMPK6 via dephosphorylation. Consistent with this finding, the suppression of mitogen-activated protein kinase genes OsMPK6, OsMKK4, and OsMKKK10 separately resulted in denser panicles and smaller grains, which rescued the mutant gsn1 phenotypes. Therefore, OsMKKK10-OsMKK4-OsMPK6 participates in panicle morphogenesis and acts on a common pathway in rice. We confirmed that GSN1 is a negative regulator of the OsMKKK10-OsMKK4-OsMPK6 cascade that determines panicle architecture. The GSN1-MAPK module coordinates the trade-off between grain number and grain size by integrating localized cell differentiation and proliferation. These findings provide important insights into the developmental plasticity of the panicle and a potential means to improve crop yields.

Beyond denitrification: The role of microbial diversity in controlling nitrous oxide reduction and soil nitrous oxide emissions.

Many biotic and abiotic processes contribute to nitrous oxide (N2 O) production in the biosphere, but N2 O consumption in the environment has heretofore been attributed primarily to canonical denitrifying microorganisms. The nosZ genes encoding the N2 O reductase enzyme, NosZ, responsible for N2 O reduction to dinitrogen are now known to include two distinct groups: the well-studied Clade I which denitrifiers typically possess, and the novel Clade II possessed by diverse groups of microorganisms, most of which are non-denitrifiers. Clade II N2 O reducers could play an important, previously unrecognized role in controlling N2 O emissions for several reasons, including: (1) the consumption of N2 O produced by processes other than denitrification, (2) hypothesized non-respiratory functions of NosZ as an electron sink or for N2 O detoxification, (3) possible differing enzyme kinetics of Clade II NosZ compared to Clade I NosZ, and (4) greater nosZ gene abundance for Clade II compared to Clade I in soils of many ecosystems. Despite the potential ecological significance of Clade II NosZ, a census of 800 peer-reviewed original research articles discussing nosZ and published from 2013 to 2019 showed that the percentage of articles evaluating or mentioning Clade II nosZ increased from 5% in 2013 to only 22% in 2019. The census revealed that the slowly spreading awareness of Clade II nosZ may result in part from disciplinary silos, with the percentage of nosZ articles mentioning Clade II nosZ ranging from 0% in Agriculture and Agronomy journals to 32% in Multidisciplinary Sciences journals. In addition, inconsistent nomenclature for Clade I nosZ and Clade II nosZ, with 17 different terminologies used in the literature, may have created confusion about the two distinct groups of N2 O reducers. We provide recommendations to accelerate advances in understanding the role of the diversity of N2 O reducers in regulating soil N2 O emissions.

Genetic variation in the SIM1 locus is associated with erectile dysfunction.

Erectile dysfunction affects millions of men worldwide. Twin studies support the role of genetic risk factors underlying erectile dysfunction, but no specific genetic variants have been identified. We conducted a large-scale genome-wide association study of erectile dysfunction in 36,649 men in the multiethnic Kaiser Permanente Northern California Genetic Epidemiology Research in Adult Health and Aging cohort. We also undertook replication analyses in 222,358 men from the UK Biobank. In the discovery cohort, we identified a single locus (rs17185536-T) on chromosome 6 near the single-minded family basic helix-loop-helix transcription factor 1 (SIM1) gene that was significantly associated with the risk of erectile dysfunction (odds ratio = 1.26, P = 3.4 × 10-25). The association replicated in the UK Biobank sample (odds ratio = 1.25, P = 6.8 × 10-14), and the effect is independent of known erectile dysfunction risk factors, including body mass index (BMI). The risk locus resides on the same topologically associating domain as SIM1 and interacts with the SIM1 promoter, and the rs17185536-T risk allele showed differential enhancer activity. SIM1 is part of the leptin-melanocortin system, which has an established role in body weight homeostasis and sexual function. Because the variants associated with erectile dysfunction are not associated with differences in BMI, our findings suggest a mechanism that is specific to sexual function.

Longibramides A-E, Peptaibols Isolated from a Mushroom Derived Fungus Trichoderma longibrachiatum Rifai DMG-3-1-1.

Five new peptaibols, longibramides A-E (1-5) with 11 amino acid residues, were isolated from a fungus Trichoderma longibrachiatum Rifai DMG-3-1-1, which was isolated from a mushroom Clitocybe nebularis (Batsch) P. Kumm collected from coniferous forest in the subboreal area of northeast China. The structures of longibramides A-E were determined by their spectroscopic data (NMR and MS-MS spectra), their absolute configurations were determined by X-ray diffractions and Marfey's analyses. The X-ray diffractions of longibramides A, B, and the similar CD spectra of A-E showed that they all had α-helix conformations. Longibramides B and E showed moderate cytotoxicities against BV2 and MCF-7 cells and also showed some inhibitory effects against methicillin-resistant Staphylococcus aureus MRSA T144. L-trans-Hyp was not commonly found in natural peptaibols, which was the 6th or 10th amino acid residue in longibramides C-E. The X-ray diffractions of longibramides A and B afforded the accuracy conformations of their secondary structures, which maybe help to interpret the structure-activity relationships of the family of peptaibols in the future.

[The level of the stress biomarker salivary alpha amylase is correlated with semen quality in infertile young men].

Objective: To investigate the relationship between the level of the stress biomarker salivary alpha amylase (SAA) and semen quality in infertile young men. METHODS: Totally, 313 infertile and 96 normal healthy men, aged 20－40 years old, were enrolled in this study. The SAA levels and semen parameters of the subjects were measured and compared between the two groups. RESULTS: Compared with the normal healthy controls, the young infertility patients showed a significantly higher SAA level (ï¼»141.04 ± 44.13ï¼½ vs ï¼»151.48 ± 38.42ï¼½ µmol/L, P < 0.05) and percentage of immotile sperm (IMS) (ï¼»39.98 ± 14.53ï¼½% vs ï¼»64.48 ± 26.32ï¼½%, P < 0.05), but lower sperm concentration (ï¼»44.23 ± 21.63ï¼½ vs ï¼»32.42 ± 23.07ï¼½ ×106/ml, P < 0.05) and percentage of progressively motile sperm (PMS) (ï¼»52.13 ± 15.42ï¼½% vs ï¼»27.91 ± 21.22ï¼½%, P < 0.05). Sperm concentration (ï¼»26.33 ± 31.83ï¼½ vs ï¼»35.28 ± 27.70ï¼½ ×106/ml, P < 0.05) and the percentage of PMS were remarkably lower in the infertile men with a high than in those with a low SAA level (ï¼»19.85 ± 21.55ï¼½% vs ï¼»31.70 ± 20.02ï¼½%, P < 0.05), while the percentage of IMS was higher in the former than in the latter group (ï¼»74.19 ± 26.84ï¼½% vs ï¼»59.92 ± 24.85ï¼½%, P < 0.05). The SAA level in the young infertility patients was correlated positively with the percentage of IMS (r = 0.170, P < 0.01), but negatively with sperm concentration (r = －0.227, P < 0.01) and the percentage of PMS (r = －0.468, P < 0.01). CONCLUSIONS: The stress biomarker salivary alpha amylase level in infertile young men is negatively correlated with semen quality, and therefore semen parameters can be improved by reducing the stress level.