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IntroductionFacing Mount Tai in the south and the Yellow River in the north, Zibo District is an important petrochemical base in China. The effect of air pollution on cardiovascular diseases (CVDs) in Zibo was unclear.MethodsDaily outpatient visits of common CVDs including coronary heart disease (CHD), stroke, and arrhythmia were obtained from 2019 to 2022 in Zibo. Air pollutants contained fine particulate matter (PM2.5), inhalable particulate matter (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), and carbon monoxide (CO). Distributed lag non-linear models (DLNM) including single-pollutant model in single-day (lag0-lag7) and cumulative-days (lag01-lag07), concentration-response curve, subgroup analysis, and double-pollutant model were utilized to examine the relationships of daily air pollutants on CHD, stroke, and arrhythmia. Meteorological factors were incorporated to control confounding.ResultsIn single-pollutant model, NO2 was positively associated with CHD, stroke and arrhythmia, with the strongest excess risks (ERs) of 4.97% (lag07), 4.71% (lag07) and 2.16% (lag02), respectively. The highest ERs of PM2.5 on CHD, stroke and arrhythmia were 0.85% (lag01), 0.59% (lag0) and 0.84% (lag01), and for PM10, the ERs were 0.37% (lag01), 0.35% (lag0) and 0.39% (lag01). SO2 on CHD was 0.92% (lag6), O3 on stroke was 0.16% (lag6), and CO on CHD, stroke, and arrhythmia were 8.77% (lag07), 5.38% (lag01), 4.30% (lag0). No threshold was found between air pollutants and CVDs. The effects of ambient pollutants on CVDs (NO2&CVDs, PM2.5&stroke, PM10&stroke, CO&stroke, CO&arrhythmia) were greater in cold season than warm season. In double-pollutant model, NO2 was positively associated with CHD and stroke, and CO was also positively related with CHD.ConclusionAmbient pollutants, especially NO2 and CO were associated with CVDs in Zibo, China. And there were strong relationships between NO2, PM2.5, PM10, CO and CVDs in cold season.

Abstract Programmed death‐ligand 1 (PD‐L1) is a critical immune checkpoint protein that facilitates tumor immune evasion. While antibody‐based PD‐1/PD‐L1 inhibitors have shown promise, their limitations necessitate the development of alternative therapeutic strategies. This work addresses these challenges by developing a hexapeptide, KFM (Lys‐Phe‐Met‐Phe‐Met‐Lys), capable of both directly downregulating PD‐L1 and self‐assembling into a ROS‐responsive supramolecular hydrogel. This dual functionality allows Gel KFM to function as a localized drug delivery system and a PD‐L1 inhibitor. Loading the hydrogel with mitoxantrone (MTX) and metformin (MET) further enhances the therapeutic effect by combining chemotherapy with PD‐L1 downregulation. In vitro and in vivo studies demonstrate significant tumor growth inhibition, increased CD8+ T cell infiltration, and reduced intratumoral PD‐L1 expression following peritumoral administration. Mechanistically, KFM promotes PD‐L1 degradation via a ubiquitin‐dependent pathway. This “carrier‐free” delivery system expands the role of supramolecular hydrogels beyond passive carriers to active immunotherapeutic agents, offering a promising new strategy for cancer therapy.

Abstract In certain cloud Electronic Medical Records (EMRs) applications, the data ownership may need to be transferred. In practice, not only the data but also the auditing ability should be transferred securely and efficiently. However, we investigate and find that most of the existing data ownership transfer protocols only work well between two individuals, and they become inefficient when dealing between two communities. The proposals for transferring tags between communities are problematic as well since, they require all members get involved or a fully trusted aggregator facilitates ownership transfer, which are unrealistic in certain scenarios. To alleviate these problems, in this paper we develop a secure auditing protocol with decentralized (t, n)-threshold ownership transfer for cloud EMRs. This protocol is designed to operate efficiently without requiring the mandatory participation of every user or the involvement of any trusted third-party. It is achieved by employing the threshold signature. Rigorous security analyses and comprehensive performance evaluations illustrate the security and practicality of our protocol. Specifically, according to the evaluations and comparisons, the communication and computational consumption is independent of the file size, i.e., it is constant in our protocol for both communities.

Depression imposes a heavy burden on patients and society, and current antidepressants often cause side effects such as dryness in the mouth and constipation. The explorations about aromatic plant essential oils provide a new method for the treatment of depression, but the mechanisms of antidepressant effect of these oils are not deeply enough. Here, the rosemary essential oil analyzed by GC-O and GC-MS techniques, whose main aromatic compounds are determined as 1,8-cineole (OAV = 1869.27, AI = 9.4), linalool (OAV = 1668.90, AI = 5.4), and ethyl decanoate (OAV = 1169.09, AI = 6.9). The network pharmacology was employed to investigate the possible pathway of action for antidepressant effects of the rosemary essential oil, and Gface software that can capture facial expressions was used to harmony the aroma to make the oil more pleasant. Then, the harmonious essential oil was proved to have antidepressant effects. For addressing issues of strong volatility and oxidation susceptibility of essential oil, dendrimer-like γ-cyclodextrin was prepared and encapsulate the essential oil. The obtained microcapsule prolonged fragrance duration and presented good stability, which are applied in aromatherapy and daily care products. This study lays a theoretical and methodological foundation for essential oil efficacy research and provides new strategies for designing and producing functional products related to essential oils.

Transition metal sulfides have drawn increasing attention as anode materials for sodium-ion batteries (SIBs) due to their high theoretical capacities. However, their practical application is still hindered by the rapid decay of capacity and severe volume variation during cycling. Herein, we constructed a hollow microspheres material composed of Co9S8-modified CoS nanosheets with the heterostructured interface through a one-step solvothermal method. When applied as the anode for SIBs, CoS/Co9S8 exhibited a superior specific capacity of 600 mAh g−1 after 100 cycles at 0.5 A g−1, and a remarkable cycling performance of 456 mAh g−1 after 1500 cycles at 5 A g−1. The outstanding electrochemical performance can be owed to the unique three-dimensional hollow hierarchical structure, which can effectively alleviate volume expansion during cycling. Moreover, density functional theory calculation further verified the improved electronic conductivity and structural stability because of the CoS/Co9S8 heterostructure.

Reducing agricultural carbon emissions (ACEs) is essential to China’s overall carbon-emission-reduction target and agricultural sustainable development. This paper analyzes the impact of agricultural technology progress (ATP) and financial support for agriculture on ACEs from a theoretical level, and empirically tests the effect of ATP on ACEs by spatial econometric model, using China’s provincial data from 2001 to 2019. The regulatory effect model is used to examine the moderating effect of financial support policies on ATP and ACEs. The sample was divided according to natural geographical environment, economic development level and agricultural production structure to study the regional heterogeneity from the spatial perspective. The main conclusions are as follows: Overall, ATP has an inhibitory effect on ACEs, and this effect has a spatial spillover effect. In terms of regulation effect, fiscal support for agriculture policy has an enhanced regulatory effect in the impact of ATP on reducing ACEs. In addition, there is obvious regional heterogeneity in the carbon emission reduction effect of ATP in the west or east of the Hu Huanyong line, western or non-western, major or non-major grain-producing regions. This paper draws the following policy implications: First, increase agricultural technology research and development and expand technology spillover channels; second, establish regional collaborative emissions reduction mechanisms and strengthen regional technical cooperation; third, improve the financial support system for agriculture; Fourth, implement regional heterogeneous agricultural policies in accordance with local conditions.

Mitotic anaphase onset is a key cellular process tightly regulated by multiple kinases. The involvement of mitogen-activated protein kinases (MAPKs) in this process has been established in Xenopus egg extracts. However, the detailed regulatory cascade remains elusive, and it is also unknown whether the MAPK-dependent mitotic regulation is evolutionarily conserved in the single-cell eukaryotic organisms such as fission yeast (Schizosaccharomyces pombe). Here, we show that two MAPKs in S. pombe indeed act in concert to restrain anaphase-promoting complex/cyclosome (APC/C) activity upon activation of the spindle assembly checkpoint (SAC). One MAPK, Pmk1, binds to and phosphorylates Slp1Cdc20, the co-activator of APC/C. Phosphorylation of Slp1Cdc20 by Pmk1, but not by Cdk1, promotes its subsequent ubiquitylation and degradation. Intriguingly, Pmk1-mediated phosphorylation event is also required to sustain SAC under environmental stress. Thus, our study establishes a new underlying molecular mechanism of negative regulation of APC/C by MAPK upon stress stimuli, and provides a previously unappreciated framework for regulation of anaphase entry in eukaryotic cells.

BackgroundChina's rapidly aging population necessitates effective strategies for ensuring older adults' quality of life (QOL). While individual factors (IF) and family factors (FF) are known to influence QOL, existing research often examines these factors in isolation or focuses on specific subpopulations, overlooking potential interactions and mediating pathways. ObjectiveThis study aims to examine both direct and indirect pathways connecting IF and FF to older adults’ QOL, focusing on the mediating roles of health risks (HR) and health care service demand (HSD). MethodsThis study uses structural equation modeling (SEM) to analyze cross-sectional data from 8600 older participants in the 2015 China Health and Retirement Longitudinal Study (CHARLS), a nationally representative study using a multistage probability proportional to size sampling method. ResultsAmong the 8600 participants, the majority (5586/8502, 65.7%) were aged 60-70 years, with a near-equal distribution of males and females at around 50%. The average PCS score was 76.77, while the MCS score averaged 59.70. Both IF (β=0.165, P

Abstract Background pOsNAR2.1:OsNAR2.1 expression could significantly increase nitrogen uptake efficiency and grain yield of rice. Result This study reported the effects of overexpression of OsNAR2.1 by OsNAR2.1 promoter on physiological and agronomic traits associated with drought tolerance. In comparison to the wild-type (WT), the pOsNAR2.1:OsNAR2.1 transgenic lines exhibited a significant improvement in survival rate when subjected to drought stress and then irrigation. Under limited water supply conditions, compared with WT, the photosynthesis and water use efficiency (WUE) of transgenic lines were increased by 39.2% and 28.8%, respectively. Finally, the transgenic lines had 25.5% and 66.4% higher grain yield than the WT under full watering and limited water supply conditions, respectively. Compared with the WT, the agronomic nitrogen use efficiency (NUE) of transgenic lines increased by 25.5% and 66.4% under full watering and limited water supply conditions, and the N recovery efficiency of transgenic lines increased by 29.3% and 50.2%, respectively. The interaction between OsNAR2.1 protein and OsPLDα1 protein was verified by yeast hybrids. After drought treatment, PLDα activity on the plasma membrane of the transgenic line increased 85.0% compared with WT. Conclusion These results indicated that pOsNAR2.1:OsNAR2.1 expression could improve the drought resistance of rice by increasing nitrogen uptake and regulating the expression of OsPLDα1.

Xixia amber from Henan Province in China has undergone a thorough examination utilizing microscopic observation, infrared spectroscopy, and three-dimensional (3D) fluorescence spectroscopy. This systematic analysis has revealed that there are primarily two varieties of Xixia amber: a light-colored type and a dark-colored type. These can be differentiated based on their coloration, infrared spectra, and distinctive fluorescence attributes. Notably, the infrared spectral profile of Xixia amber features a prominent peak at 1023 cm−1, accompanied by less pronounced peaks at 1088 and 974 cm−1. These spectral characteristics set it apart from amber originating from the Baltic regions, Myanmar, and Fushun. Further distinction is achieved through 3D fluorescence spectra, where Xixia amber exhibits similarities to Burmese and Fushun ambers. Chemical classification via pyrolysis gas chromatography-mass spectrometry (Py-GC-MS) identifies Xixia amber as belonging to Class Ib, characterized by its ordered structure and the absence of succinic acid. This comprehensive study delineates the coloration, infrared spectral properties, photoluminescent behavior, and chemical compositions of Xixia amber, clearly differentiating it from ambers sourced from other geographical locations.

Abstract Background Gliomas are recognized as the most frequent type of malignancies in the central nervous system, and efficacious prognostic indicators are essential to treat patients with gliomas and improve their clinical outcomes. The chemokine (C‐C motif) ligand 2 (CCL2) is a promising predictor for glioma malignancy and progression. However, at present, the methods to evaluate CCL2 expression level are invasive and operator‐dependent. Objective It was expected to noninvasively predict CCL2 expression levels in malignant glioma tissues by magnetic resonance imaging (MRI)‐based radiomics and assess the association between the developed radiomics model and prognostic indicators and related genes. Methods MRI‐based radiomics was used to predict CCL2 expression level using data obtained from The Cancer Imaging Archive (TCIA) and The Cancer Genome Atlas (TCGA) databases. A support vector machine (SVM)‐based radiomics model and a logistic regression (LR)‐based radiomics model were used to predict the radiomics score, and its correlation with CCL2 expression level was analyzed. Results The results revealed that there was an association between CCL2 expression level and the overall survival of cases with gliomas, and bioinformatics correlation analysis showed that CCL2 expression level was highly correlated with disease‐related pathways, such as mTOR signaling pathway, cGMP‐PKG signaling pathway, and MAPK signaling pathway. Both SVM‐ and LR‐based radiomics data robustly predicted CCL2 expression level, and radiomics scores could also be used to predict the overall survival of patients. Moreover, the high/low radiomics scores were highly correlated with the known glioma‐related genes, including CD70, CD27, and PDCD1. Conclusion An MRI‐based radiomics model was successfully developed, and its clinical benefits were confirmed, including the prediction of CCL2 expression level and patients' prognosis.

Summary: Background: Macrophages are innate immune cells whose phagocytosis function is critical to the prognosis of stroke and peritonitis. cis-aconitic decarboxylase immune-responsive gene 1 (Irg1) and its metabolic product itaconate inhibit bacterial infection, intracellular viral replication, and inflammation in macrophages. Here we explore whether itaconate regulates phagocytosis. Methods: Phagocytosis of macrophages was investigated by time-lapse video recording, flow cytometry, and immunofluorescence staining in macrophage/microglia cultures isolated from mouse tissue. Unbiased RNA-sequencing and ChIP-sequencing assays were used to explore the underlying mechanisms. The effects of Irg1/itaconate axis on the prognosis of intracerebral hemorrhagic stroke (ICH) and peritonitis was observed in transgenic (Irg1flox/flox; Cx3cr1creERT/+, cKO) mice or control mice in vivo. Findings: In a mouse model of ICH, depletion of Irg1 in macrophage/microglia decreased its phagocytosis of erythrocytes, thereby exacerbating outcomes (n = 10 animals/group, p

Accumulation of reactive oxygen species (ROS), especially on lipids, induces massive cell death in neurons and oligodendrocyte progenitor cells (OPCs) and causes severe neurologic deficits post stroke. While small compounds, such as deferoxamine, lipostatin-1, and ferrostatin-1, have been shown to be effective in reducing lipid ROS, the mechanisms by which endogenously protective molecules act against lipid ROS accumulation and subsequent cell death are still unclear, especially in OPCs, which are critical for maintaining white matter integrity and improving long-term outcomes after stroke. Here, using mouse primary OPC cultures, we demonstrate that interleukin-10 (IL-10), a cytokine playing roles in reducing neuroinflammation and promoting hematoma clearance, significantly reduced hemorrhage-induced lipid ROS accumulation and subsequent ferroptosis in OPCs. Mechanistically, IL-10 activated the IL-10R/STAT3 signaling pathway and upregulated the DLK1/AMPK/ACC axis. Subsequently, IL-10 reprogrammed lipid metabolism and reduced lipid ROS accumulation. In addition, in an autologous blood injection intracerebral hemorrhagic stroke (ICH) mouse model, deficiency of the endogenous Il-10, specific knocking out Il10r or Dlk1 in OPCs, or administration of ACC inhibitor was associated with increased OPC cell death, demyelination, axonal sprouting, and the cognitive deficits during the chronic phase of ICH and vice versa. These data suggest that IL-10 protects against OPC loss and white matter injury by reducing lipid ROS, supporting further development of potential clinical applications to benefit patients with stroke and related disorders.

Promoting equal access to public services and improving people's well-being is a key link in building a modern national governance system in China. However, under the Chinese-style fiscal decentralization system, local governments face the “dilemma” of economic growth goals and the improvement of people's livelihoods. China's basic public services still have the problems of insufficient supply quantity, unbalanced structure and low efficiency. This paper aims to explore the impact of fiscal decentralization and local government competition on basic public services, and provide a theoretical and practical basis for deepening the reform of China's fiscal and taxation system, perfecting the transfer payment system, and improving the public service provision at the present stage. Under the premise of theoretical hypothesis, based on the panel data of 178 prefecture-level cities in China from 2008 to 2019, which is obtained from the Statistical Yearbook and the Work report of prefecture-level governments, the fixed effect model and threshold model are used for the empirical test. The results show that: first, the increase of fiscal decentralization has a negative impact on supply of basic public services in prefecture-level cities; second, the local government competition aiming at economic growth will intensify the negative impact, and make the relationship between fiscal decentralization and basic public services show nonlinear characteristics; Third, compared with developed areas, the strengthening regulatory effect of local government competition is more obvious in less-developed areas, such as western and northeastern regions, and third-tier, fourth-tier, and fifth-tier cities. Based on these findings, this paper draws the following policy implications: strengthen the reform of the fiscal and taxation system below the provincial level, promote the construction of a direct transfer payment mechanism, adjust the standards and methods of performance appraisal, and use modern information technology to improve the public service demand and interest expression mechanisms.

Eukaryotic cells are constantly exposed to various environmental stimuli. It remains largely unexplored how environmental cues bring about epigenetic fluctuations and affect heterochromatin stability. In the fission yeast Schizosaccharomyces pombe, heterochromatic silencing is quite stable at pericentromeres but unstable at the mating-type (mat) locus under chronic heat stress, although both loci are within the major constitutive heterochromatin regions. Here, we found that the compromised gene silencing at the mat locus at elevated temperature is linked to the phosphorylation status of Atf1, a member of the ATF/CREB superfamily. Constitutive activation of mitogen-activated protein kinase (MAPK) signaling disrupts epigenetic maintenance of heterochromatin at the mat locus even under normal temperature. Mechanistically, phosphorylation of Atf1 impairs its interaction with heterochromatin protein Swi6HP1, resulting in lower site-specific Swi6HP1 enrichment. Expression of non-phosphorylatable Atf1, tethering Swi6HP1 to the mat3M-flanking site or absence of the anti-silencing factor Epe1 can largely or partially rescue heat stress-induced defective heterochromatic maintenance at the mat locus.

IntroductionAlzheimer’s disease (AD) is the most prevalent neurodegenerative disease characterized by extracellular senile plaques including amyloid-β peptides and intracellular neurofibrillary tangles consisting of abnormal Tau. Depression is one of the most common neuropsychiatric symptoms in AD, and clinical evidence demonstrates that depressive symptoms accelerate the cognitive deficit of AD patients. However, the underlying molecular mechanisms of depressive symptoms present in the process of AD remain unclear.MethodsDepressive-like behaviors and cognitive decline in hTau mice were induced by chronic restraint stress (CRS). Computational prediction and molecular experiments supported that an asparagine endopeptidase (AEP)-derived Tau fragment, Tau N368 interacts with peroxisome proliferator-activated receptor delta (PPAR-δ). Further behavioral studies investigated the role of Tau N368-PPAR-δ interaction in depressive-like behaviors and cognitive declines of AD models exposed to CRS.ResultsWe found that mitochondrial dysfunction was positively associated with depressive-like behaviors and cognitive deficits in hTau mice. Chronic stress increased Tau N368 and promoted the interaction of Tau N368 with PPAR-δ, repressing PPAR-δ–mediated transactivation in the hippocampus of mice. Then we predicted and identified the binding sites of PPAR-δ. Finally, inhibition of AEP, clearance of Tau N368 and pharmacological activation of PPAR-δ effectively alleviated CRS-induced depressive-like behaviors and cognitive decline in mice.ConclusionThese results demonstrate that Tau N368 in the hippocampus impairs mitochondrial function by suppressing PPAR-δ, facilitating the occurrence of depressive-like behaviors and cognitive decline. Therefore, our findings may provide new mechanistic insight in the pathophysiology of depression-like phenotype in mouse models of Alzheimer’s disease.

Introduction There are limited data on the management of bone health, including bone mineral density (BMD) evaluation and osteoporosis (OP) treatment, in patients undergoing elective orthopaedic surgeries. Methods This was a retrospective cohort study using administrative claims data from Symphony Health, PatientSource for patients aged ≥50 years with documented kyphoplasty/vertebroplasty (KP/VP), total knee arthroplasty (TKA), and total hip arthroplasty (THA). Risk stratification to identify patients at very high risk for fracture (VHRFx) was based on clinical practice guideline recommendations to the extent information on variables of interest were available from the claims database. Results A total of 251 919 patients met inclusion criteria: KP/VP (31 018), TKA (149 849), and THA (71 052). The majority were female (80.3%) with a mean (SD) age of 68.5 (7.5) years. Patients undergoing KP/VP were older and had a greater comorbidity burden associated with risk for falls, mobility issues, muscle weakness, and respiratory and cardiovascular diseases. In the 6 months before surgery, 11.8% of patients were tested and/or received treatment for OP. Patients undergoing KP/VP were more likely to be tested and/or treated (17.5%) than patients undergoing TKA (11.0%) or THA (10.9%). Overall, men had a lower rate of testing and/or treatment than women (4.6% vs 13.5%). In the 12 months before surgery, patients with an OP diagnosis and at VHRFx (30.8%) had a higher rate of treatment and/or testing than those without OP (11.5%), or those without OP but with a fracture in the year preceding surgery (10.2%). Conclusions Bone health management is suboptimal in patients undergoing elective orthopaedic surgeries and is worse in men than in women. Proper management of OP before and after surgery may improve outcomes.

Identifying loci for root system architecture (RSA) traits and developing available markers are crucial for wheat breeding. In this study, RSA-related traits, including total root length (TRL), total root area (TRA), and number of root tips (NRT), were evaluated in the Doumai/Shi4185 recombinant inbred line (RIL) population under hydroponics. In addition, both the RILs and parents were genotyped using the wheat 90K single-nucleotide polymorphism (SNP) array. In total, two quantitative trait loci (QTLs) each for TRL (QTRL.caas-4A.1 and QTRL.caas-4A.2), TRA (QTRA.caas-4A and QTRA.caas-4D), and NRT (QNRT.caas-5B and QNRT.caas-5D) were identified and each explaining 5.94%–9.47%, 6.85%–7.10%, and 5.91%–10.16% phenotypic variances, respectively. Among these, QTRL.caas-4A.1 and QTRA.caas-4A overlapped with previous reports, while QTRL.caas-4A.2, QTRA.caas-4D, QNRT.caas-5B, and QNRT.caas-5D were novel. The favorable alleles of QTRL.caas-4A.1, QTRA.caas-4A, and QTRA.caas-5B were contributed by Doumai, whereas the favorable alleles of QTRL.caas-4A.2, QTRA.caas-4D, and QTRA.caas-5D originated from Shi 4185. Additionally, two competitive allele-specific PCR (KASP) markers, Kasp_4A_RL (QTRA.caas-4A) and Kasp_5D_RT (QNRT.caas-5D), were developed and validated in 165 wheat accessions. This study provides new loci and available KASP markers, accelerating wheat breeding for higher yields.

The Meso-Cenozoic tectonic activities of the Central Asian Orogenic Belt (CAOB) played an important role in controlling the present-day topography of Central Asia. The Altai orogenic belt is a key component in the southern CAOB; so far, there is still a lack of sufficient constraints on the time and mechanism of its tectonic reactivation since the Mesozoic. In this contribution, we present new zircon and apatite (U-Th)/He and apatite fission track thermochronological data from granitoid samples in the Habahe area, western Altai orogenic belt. Therein zircon (U-Th)/He ages range from ~230 to ~238 Ma, apatite fission track central ages are ~140–157 Ma, and apatite (U-Th)/He ages vary from ~134 to ~149 Ma. Based on the associated thermal history modeling results, the Habahe area underwent a moderate cooling during the Late Triassic to Middle Jurassic (~230–170 Ma) with a cooling rate of ~0.8–1.1℃/Ma and a subsequent moderate to slightly rapid cooling stage during the Middle Jurassic to Early Cretaceous (170–130 Ma) with a cooling rate of ~1.5–2.3℃/Ma. We propose that this prolonged cooling stage occurred under a long-lasting contractional tectonism in the western Altai throughout the early Mesozoic, which was produced by multiplate convergence in East Asia during this period, mainly including the consumption of the Mongol-Okhotsk Ocean in the northeast and the Meso-Tethys Ocean in the south. The region experienced rather limited Late Cretaceous-Cenozoic cooling and exhumation due to insufficient reactivation and weak surficial erosion.

The microtubule plus-end tracking protein Tip1 regulates microtubule dynamics and polar growth in fission yeast. Here the authors link the ubiquitination of Tip1 by ubiquitin ligase Dma1 to polarized growth inhibition upon DNA replication stress.

Germplasm conserved in gene banks is underutilized, owing mainly to the cost of characterization. Genomic prediction can be applied to predict the genetic merit of germplasm. Germplasm utilization could be greatly accelerated if prediction accuracy were sufficiently high with a training population of practical size. Large-scale resequencing projects in rice have generated high quality genome-wide variation information for many diverse accessions, making it possible to investigate the potential of genomic prediction in rice germplasm management and exploitation. We phenotyped six traits in nearly 2000 indica (XI) and japonica (GJ) accessions from the Rice 3K project and investigated different scenarios for forming training populations. A composite core training set was considered in two levels which targets used for prediction of subpopulations within subspecies or prediction across subspecies. Composite training sets incorporating 400 or 200 accessions from either subpopulation of XI or GJ showed satisfactory prediction accuracy. A composite training set of 600 XI and GJ accessions showed sufficiently high prediction accuracy for both XI and GJ subspecies. Comparable or even higher prediction accuracy was observed for the composite training set than for the corresponding homogeneous training sets comprising accessions only of specific subpopulations of XI or GJ (within-subspecies level) or pure XI or GJ accessions (across-subspecies level) that were included in the composite training set. Validation using an independent population of 281 rice cultivars supported the predictive ability of the composite training set. Reliability, which reflects the robustness of a training set, was markedly higher for the composite training set than for the corresponding homogeneous training sets. A core training set formed from diverse accessions could accurately predict the genetic merit of rice germplasm.

Wood is a naturally porous material prone to microbial erosion and degradation in outdoor environments. Therefore, the development of an environmentally friendly wood preservative with excellent antibacterial effects and low toxicity is urgently needed. In this study, nitrogen-doped carbon quantum dots (N-CQDs) with excellent antifungal performance and fluorescent properties were synthesized using a one-step hydrothermal method with chitosan quaternary ammonium salt (HACC) as the raw material. The fluorescence characteristics of N-CQD preservatives can help track their position and distribution in wood. The minimum inhibitory concentration (MIC) of N-CQDs is 1.8 mg/mL, which was nearly 22 times lower than that of HACC (40.0 mg/mL) in the PDA medium. The decay resistance test demonstrated that wood treated with N-CQDs showed a considerably reduced decay degree and its mass loss rate decreased from 46 ± 0.5% to 3.8 ± 0.5%. Biological transmission electron microscopy revealed that N-CQDs effectively destroyed fungal cell structures, thereby hindering the growth of Coriolus versicolor. N-CQDs synthesized using the one-step hydrothermal method can be used as an efficient wood preservative that can effectively improve the utilization and service life of wood.

Mesocotyl is an essential organ of rice for pushing buds out of soil and plays a crucial role in seeding emergence and development in direct-seeding. Thus, identify the loci associated with mesocotyl length (ML) could accelerate breeding progresses for direct-seeding cultivation. Mesocotyl elongation was mainly regulated by plant hormones. Although several regions and candidate genes governing ML have been reported, the effects of them in diverse breeding populations were still indistinct. In this study, 281 genes related to plant hormones at the genomic regions associated with ML were selected and evaluated by single-locus mixed linear model (SL-MLM) and multi-locus random-SNP-effect mixed linear model (mr-MLM) in two breeding panels (Trop and Indx) originated from the 3K re-sequence project. Furthermore, superior haplotypes with longer mesocotyl were also identified for marker assisted selection (MAS) breeding. Totally, LOC_Os02g17680 (explained 7.1-8.9% phenotypic variations), LOC_Os04g56950 (8.0%), LOC_Os07g24190 (9.3%) and LOC_Os12g12720 (5.6-8.0%) were identified significantly associated with ML in Trop panel, whereas LOC_Os02g17680 (6.5-7.4%), LOC_Os04g56950 (5.5%), LOC_Os06g24850 (4.8%) and LOC_Os07g40240 (4.8-7.1%) were detected in Indx panel. Among these, LOC_Os02g17680 and LOC_Os04g56950 were identified in both panels. Haplotype analysis for the six significant genes indicated that haplotype distribution of the same gene varies at Trop and Indx panels. Totally, 8 (LOC_Os02g17680-Hap1 and Hap2, LOC_Os04g56950-Hap1, Hap2 and Hap8, LOC_Os07g24190-Hap3, LOC_Os12g12720-Hap3 and Hap6) and six superior haplotypes (LOC_Os02g17680-Hap2, Hap5 and Hap7, LOC_Os04g56950-Hap4, LOC_Os06g24850-Hap2 and LOC_Os07g40240-Hap3) with higher ML were identified in Trop and Indx panels, respectively. In addition, significant additive effects for ML with more superior haplotypes were identified in both panels. Overall, the 6 significantly associated genes and their superior haplotypes could be used to enhancing ML through MAS breeding and further promote direct-seedling cultivation.

Rice bran is a high-quality and renewable livestock feed material rich in nutrients and bioactive substances. To investigate the effects of dietary supplementation with fermented heat-treated rice bran on the performance, apparent digestibility of nutrients, cecal microbiota and metabolites in laying hens, a total of 128 18-week-old Hy-Line brown layers were randomly assigned to four treatment groups: 2.5% HRB (basal diet contained 2.5% heat-treated rice bran), 5.0% HRB (5.0% heat-treated rice bran), 2.5% FHRB (2.5% fermented heat-treated rice bran), 5.0% FHRB (5.0% fermented heat-treated rice bran). Results showed that FHRB supplementation significantly increased the average daily feed intake (ADFI) during 25–28 weeks, and improved apparent digestibility of dry matter (DM), crude protein (CP), ether extract (EE) and crude fiber (CF) in laying hens. Moreover, feeding 5.0% of HRB and FHRB resulted higher egg production (EP) and average egg weight (AEW) during the feeding period, and decreased the feed conversion ratio (FCR) during 21 to 28 weeks. The alpha and beta diversity indices indicated that FHRB altered the cecal microbiota. In particular, dietary supplementation with FHRB significantly increased the relative abundances of Lachnospira and Clostridium. Compared with the 2.5% level of supplementation, supplementing 5.0% HRB and 5.0% FHRB increased the relative abundances of Firmicutes, Ruminococcus and Peptococcus, and lowered the relative abundance of Actinobacteria. Furthermore, dietary FHRB supplementation significantly increased the concentration of short-chain fatty acids in cecum and changed the overall metabolome. The results of correlation analysis showed a close interaction between cecal microbiota, metabolites and apparent digestibility of nutrients. Taken together, we revealed that FHRB supplementation can induce characteristic structural and metabolic changes in the cecal microbiome, which could potentially promote nutrient digestion and absorption, and improve the production performance of laying hens.

Abstract Oligodendrocyte progenitor cells (OPCs) differentiate to myelin-producing mature oligodendrocytes and enwrap growing or demyelinated axons during development and post central nervous diseases. Failure of remyelination owing to cell death or undifferentiation of OPCs contributes to severe neurologic deficits and motor dysfunction. However, how to prevent the cell death of OPCs is still poorly understood, especially in hemorrhagic diseases. In the current study, we injected autologous blood into the mouse lateral ventricular to study the hemorrhage-induced OPC cell death in vivo. The integrity of the myelin sheath of the corpus callosum was disrupted post intraventricular hemorrhage (IVH) assessed by using magnetic resonance imaging, immunostaining, and transmission electron microscopy. Consistent with the severe demethylation, we observed massive cell death of oligodendrocyte lineages in the periventricular area. In addition, we found that ferroptosis is the major cell death form in Hemin-induced OPC death by using RNA-seq analysis, and the mechanism was glutathione peroxidase 4 activity reduction-resulted lipid peroxide accumulation. Furthermore, inhibition of ferroptosis rescued OPC cell death in vitro, and in vivo attenuated IVH-induced white matter injury and promoted recovery of neurological function. These data demonstrate that ferroptosis is an essential form of OPC cell death in hemorrhagic stroke, and rescuing ferroptotic OPCs could serve as a therapeutic target for stroke and related diseases.

Plant-derived preservatives exhibit excellent antifungal effects. However, their antifungal active ingredients can easily leach out. A properly designed functional response system can help realize the responsive release of preservatives and reduce leaching. Herein, the pH-responsive preservatives delivery system was designed and synthesized. The preservative (Forsythia) was encapsulated with hollow mesoporous organosilica nanoparticles (HMONs), and carbon quantum dots (CQDs) were employed as mesoporous plugging agents. Forsythia’s release was achieved by grafting pH-sensitive chemical bonds on the surface of the carrier. X-ray photoelectron spectroscopy and antifungal results showed that the pH-responsive switch was successfully broken. After 12 weeks of soil-jar incubation, the weight loss rate of treated wood was 2 % ± 0.5 %. The leaching of Forsythia–HMON–CQDs was lower than that of Forsythia under the same concentration. The design of the system reduced the leaching of Forsythia and extended the service life of wood. In addition, the system was also applicable to ammoniacal copper quat (ACQ). Forsythia–HMON–CQDs showed an outstanding fixation effect and antifungal ability, and its fluorescence can be used to track distribution in wood. This system can be extensively employed in protecting antifungal active ingredients and demonstrates an effective strategy for developing potential bio-based wood preservatives.

Abstract Background Panax notoginseng (Burk.) F. H. Chen (P. notoginseng) is a medicinal plant. Cytochrome P450 (CYP450) monooxygenase superfamily is involved in the synthesis of a variety of plant hormones. Studies have shown that CYP450 is involved in the synthesis of saponins, which are the main medicinal component of P. notoginseng. To date, the P. notoginseng CYP450 family has not been systematically studied, and its gene functions remain unclear. Results In this study, a total of 188 PnCYP genes were identified, these genes were divided into 41 subfamilies and clustered into 9 clans. Moreover, we identified 40 paralogous pairs, of which only two had Ka/Ks ratio greater than 1, demonstrating that most PnCYPs underwent purification selection during evolution. In chromosome mapping and gene replication analysis, 8 tandem duplication and 11 segmental duplication events demonstrated that PnCYP genes were continuously replicating during their evolution. Gene ontology (GO) analysis annotated the functions of 188 PnCYPs into 21 functional subclasses, suggesting the functional diversity of these gene families. Functional divergence analyzed the members of the three primitive branches of CYP51, CYP74 and CYP97 at the amino acid level, and found some critical amino acid sites. The expression pattern of PnCYP450 related to nitrogen treatment was studied using transcriptome sequencing data, 10 genes were significantly up-regulated and 37 genes were significantly down-regulated. Combined with transcriptome sequencing analysis, five potential functional genes were screened. Quantitative real-time PCR (qRT-PCR) indicated that these five genes were responded to methyl jasmonate (MEJA) and abscisic acid (ABA) treatment. Conclusions These results provide a valuable basis for comprehending the classification and biological functions of PnCYPs, and offer clues to study their biological functions in response to nitrogen treatment.

Depression, one of the most common causes of disability, has a high prevalence rate in patients with metabolic syndrome. Type 2 diabetes patients are at an increased risk for depression. However, the molecular mechanism coupling diabetes to depressive disorder remains largely unknown. Here we found that the neuroinflammation, associated with high-fat diet (HFD)-induced diabetes and obesity, activated the transcription factor CCAAT/enhancer binding protein β (C/EBPβ) in hippocampal neurons. This factor repressed brain-derived neurotrophic factor (BDNF) expression and caused depression-like behaviors in male mice. Besides, the loss of C/EBPβ expression in C/EBPβ heterozygous knockout male mice attenuated HFD-induced depression-like behaviors, whereas Thy1-C/EBPβ transgenic male mice (overexpressing C/EBPβ) showed depressive behaviors after a short-term HFD. Furthermore, HFD impaired synaptic plasticity and decreased surface expression of glutamate receptors in the hippocampus of wild-type (WT) mice, but not in C/EBPβ heterozygous knockout mice. Remarkably, the anti-inflammatory drug aspirin strongly alleviated HFD-elicited depression-like behaviors in neuronal C/EBPβ transgenic mice. Finally, the genetic delivery of BDNF or the pharmacological activation of the BDNF/TrkB signaling pathway by 7,8-dihydroxyflavone reversed anhedonia in a series of behavioral tests on HFD-fed C/EBPβ transgenic mice. Therefore, our findings aim to demonstrate that the inflammation-activated neuronal C/EBPβ promotes HFD-induced depression by diminishing BDNF expression.

The eukaryotic multisubunit Elongator complex has been shown to perform multiple functions in transcriptional elongation, histone acetylation and tRNA modification. However, the Elongator complex plays different roles in different organisms, and the underlying mechanisms remain unexplored. Moreover, the biological functions of the Elongator complex in human fungal pathogens remain unknown. In this study, we verified that the Elongator complex of the opportunistic fungal pathogen Aspergillus fumigatus consists of six subunits (Elp1-6), and the loss of any subunit results in similarly defective colony phenotypes with impaired hyphal growth and reduced conidiation. The catalytic subunit-Elp3 of the Elongator complex includes a S-adenosyl methionine binding (rSAM) domain and a lysine acetyltransferase (KAT) domain, and it plays key roles in the hyphal growth, biofilm-associated exopolysaccharide galactosaminogalactan (GAG) production, adhesion and virulence of A. fumigatus; however, Elp3 does not affect H3K14 acetylation levels in vivo. LC-MS/MS chromatograms revealed that loss of Elp3 abolished the 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U) modification of tRNA wobble uridine (U34), and the overexpression of tRNAGlnUUG and tRNAGluUUC, which normally harbor mcm5s2U modifications, mainly rescues the defects of the Δelp3 mutant, suggesting that tRNA modification rather than lysine acetyltransferase is responsible for the primary function of Elp3 in A. fumigatus. Strikingly, global proteomic comparison analyses showed significantly upregulated expression of genes related to amino acid metabolism in the Δelp3 mutant strain compared to the wild-type strain. Western blotting showed that deletion of elp3 resulted in overexpression of the amino acid starvation-responsive transcription factor CpcA, and deletion of CpcA markedly reversed the defective phenotypes of the Δelp3 mutant, including attenuated virulence. Therefore, the findings of this study demonstrate that A. fumigatus Elp3 functions as a tRNA-modifying enzyme in the regulation of growth, GAG production, adhesion and virulence by maintaining intracellular amino acid homeostasis. More broadly, our study highlights the importance of U34 tRNA modification in regulating cellular metabolic states and virulence traits of fungal pathogens.

Brain derived neurotrophic factor (BDNF) has multiple biological functions which are mediated by the activation of two receptors, tropomyosin receptor kinase B (TrkB) receptor and the p75 neurotrophin receptor, involving in physiological and pathological processes throughout life. The diverse presence and activity of BDNF indicate its potential role in the pathogenesis, progression and treatment of both neurological and psychiatric disorders. This review is to provide a comprehensive assessment of the current knowledge and future directions in BDNF-associated research in the central nervous system (CNS), with an emphasis on the physiological and pathological functions of BDNF as well as its potential treatment effects in CNS diseases, including depression, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, multiple sclerosis, and cerebral ischemic stroke.

The activated spindle assembly checkpoint (SAC) potently inhibits the anaphase-promoting complex/cyclosome (APC/C) to ensure accurate chromosome segregation at anaphase. Early studies have recognized that the SAC should be silenced within minutes to enable rapid APC/C activation and synchronous segregation of chromosomes once all kinetochores are properly attached, but the underlying silencers are still being elucidated. Here, we report that the timely silencing of SAC in fission yeast requires dnt1+, which causes severe thiabendazole (TBZ) sensitivity and increased rate of lagging chromosomes when deleted. The absence of Dnt1 results in prolonged inhibitory binding of mitotic checkpoint complex (MCC) to APC/C and attenuated protein levels of Slp1Cdc20, consequently slows the degradation of cyclin B and securin, and eventually delays anaphase entry in cells released from SAC activation. Interestingly, Dnt1 physically associates with APC/C upon SAC activation. We propose that this association may fend off excessive and prolonged MCC binding to APC/C and help to maintain Slp1Cdc20 stability. This may allow a subset of APC/C to retain activity, which ensures rapid anaphase onset and mitotic exit once SAC is inactivated. Therefore, our study uncovered a new player in dictating the timing and efficacy of APC/C activation, which is actively required for maintaining cell viability upon recovery from the inhibition of APC/C by spindle checkpoint.

Abstract Background Elacestrant is an oral selective estrogen receptor (ER) degrader. This phase 1b open-label, non-randomized study (RAD1901-106) was initiated to determine the effect of elacestrant on the availability of ER in lesions from postmenopausal women with ER+ advanced breast cancer (ABC) using 16α-18F-fluoro-17β-estradiol positron emission tomography with low-dose computed tomography (FES-PET/CT). Methods Eligible patients were postmenopausal women with ER+, HER2− ABC; tumor progression after ≥ 6 months of 1–3 lines of endocrine treatment for ABC; and measurable or evaluable disease. Two 8-patient cohorts were enrolled: one treated with 400 mg elacestrant once daily (QD) and one treated with 200 mg elacestrant QD with dose escalation to 400 mg QD after 14 days. Elacestrant was dosed continuously until progressive disease, toxicity, or withdrawal. FES-PET/CT was performed pre-dose at baseline and 4 h post-dose on day 14. The primary endpoint was the percentage difference in FES uptake in tumor lesions (maximum 20) after 14 days of treatment compared to baseline. Overall response was investigator-assessed by Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1. Results Patients (n = 16; median age, 53.5 years) had ABC with a median 2.5 prior lines of endocrine therapy. Median reduction in tumor FES uptake from baseline to day 14 was 89.1% (Q1, Q3: 75.1%, 94.1%) and was similar in both cohorts (89.1% [Q1, Q3: 67.4%, 94.2%], 200/400 mg and 88.7% [Q1, Q3: 79.5%, 94.1%], 400 mg). Residual ER availability (> 25% persistence in FES uptake) on day 14 was observed in 3 patients receiving 200/400 mg (3/78, 37.5%) and 1 patient receiving 400 mg (1/8, 12.5%). The overall response rate (ORR) was 11.1% (1 partial response), and clinical benefit rate (CBR) was 30.8%. Median percentage change in FES uptake did not correlate with ORR or CBR. Adverse events occurring in > 20% of the patients were nausea (68.8%), fatigue (50.0%), dyspepsia (43.8%), vomiting (37.5%), and decreased appetite, dysphagia, and hot flush (31.3% each). Most events were grade 2 in severity. Conclusion Elacestrant 200 mg and 400 mg QD greatly reduced ER availability measured by FES-PET/CT. In a heavily pretreated population, elacestrant was associated with antitumor activity. Trial registration ClinicalTrials.gov, NCT02650817 . Registered on 08 January 2016

ABSTRACT Fungal diseases have become a major public health issue worldwide. Increasing drug resistance and the limited number of available antifungals result in high morbidity and mortality. Metal-based drugs have been reported to be therapeutic agents against major protozoan diseases, but knowledge of their ability to function as antifungals is limited. In this study, we found that calcium supplementation combined with iron deficiency causes dramatic growth inhibition of the human fungal pathogens Aspergillus fumigatus, Candida albicans, and Cryptococcus neoformans. Calcium induces the downregulation of iron uptake-related genes and, in particular, causes a decrease in the expression of the transcription factor HapX, which tends to transcriptionally activate siderophore-mediated iron acquisition under iron-deficient conditions. Iron deficiency causes calcium overload and the overproduction of intracellular reactive oxygen species (ROS), and perturbed ion homeostasis suppresses fungal growth. These phenomena are consistently identified in azole-resistant A. fumigatus isolates. The findings here imply that low iron availability lets cells mistakenly absorb calcium as a substitute, causing calcium abnormalities. Thus, there is a mutual effect between iron and calcium in fungal pathogens, and the combination of calcium with an iron chelator could serve to improve antifungal therapy. IMPORTANCE Millions of immunocompromised people are at a higher risk of developing different types of severe fungal diseases. The limited number of antifungals and the emergence of antimicrobial resistance highlight an urgent need for new strategies against invasive fungal infections. Here, we report that calcium can interfere with iron absorption of fungal pathogens, especially in iron-limited environments. Thus, a combination of calcium supplementation with an iron chelator inhibits the growth of human fungal pathogens, including Aspergillus fumigatus, Candida albicans, and Cryptococcus neoformans. Moreover, we demonstrate that iron deficiency induces a nonspecific calcium uptake response, which results in toxic levels of metal. Findings in this study suggest that a microenvironment with excess calcium and limited iron is an efficient strategy to curb the growth of fungal pathogens, especially for drug-resistant isolates.

Diabetic hyperglycemia aggravates the prognosis of intracerebral hemorrhagic stroke (ICH) in the clinic. In addition to hematoma expansion and increased inflammation, how diabetic hyperglycemia affects the outcomes of ICH is still unclear. We found that streptozotocin-induced diabetic hyperglycemia not only increased neutrophil infiltration, but also changed the gene expression profile of neutrophils, including lactoferrin (Ltf) encoding gene Ltf. Peroxisome proliferator-activated receptor γ (PPARγ) transcribed Ltf and the lack of neutrophilic Ltf transcription and secretion exacerbated neuronal ferroptosis by accumulating intraneuronal iron. Furthermore, the administration of recombinant Ltf protected against neuronal ferroptosis and improved neurobehavior in hyperglycemic ICH mice, and vice versa. These results indicate that supplementing Ltf or inhibiting neuronal ferroptosis are promising potential strategies to improve the acute outcomes of diabetic ICH in the clinic.

ABSTRACT Previous subgroup analyses from the ACTIVE trial in women with postmenopausal osteoporosis (NCT01343004) using three‐dimensional (3D)‐processing of dual X‐ray absorptiometry (DXA) scans indicated greater increases in total hip cortical volumetric bone mineral density (Ct.vBMD) and estimated indices of hip strength following 18 months of abaloparatide (ABL) versus placebo or teriparatide. The current post hoc analyses describe hip 3D‐DXA data for ACTIVExtend (NCT01657162), in which 18 months of ABL followed by 24 months of alendronate (ABL/ALN) increased hip and spine areal BMD (aBMD) and reduced fracture risk versus placebo (PBO) followed by ALN (PBO/ALN). In an ACTIVExtend subgroup (ABL/ALN, n = 204; PBO/ALN, n = 202), hip DXA scans retrospectively underwent 3D modeling via 3D‐Shaper software. Changes from baseline in cortical and trabecular compartments were calculated for total hip and hip subregions (femoral neck, trochanter, and shaft). Estimated strength indices comprising cross‐sectional moment of inertia, section modulus, and buckling ratio were calculated for each hip subregion. Correlations between bone turnover marker levels at the time of alendronate initiation and subsequent BMD gains with alendronate were also investigated within each group. Total hip trabecular and cortical 3D‐DXA parameters increased from baseline in both groups (all p

Though miniscrews are widely used as a temporary anchorage device, research focusing on the primary stability of miniscrew loading torque force is limited. This study is aimed to design a novel torque-resistant miniscrew used as orthodontic anchorage (TRO-screws) and to compare the difference of primary stability between TRO-screws and commercial miniscrew anchorage (COM-screws) using torque tests and resonance frequency analysis (RFA). Fresh swine ribs were cut into pieces of 20 mm × 13 mm × 11 mm, and each piece was implanted with one screw after a 1.5 mm-deep hole with a diameter of 1.0 mm was pre-drilled. There were 20 TRO-screws and 20 COM-screws. Maximum insertion torque (MIT) and maximum removal torque (MRT) were measured. The implant stability quotient (ISQ) was recorded parallel to and perpendicular to the long axis of teeth respectively. The measurement was repeated three times for each direction, and the ISQ values were averaged and recorded as the ISQpar, ISQper, and ISQm. The mean values of MIT for TRO-screws and COM-screws were 11.86±1.58 N cm and 10.36±1.42 N cm. The mean values of MRT for TRO-screws and COM-screws were 8.45±2.24 N cm and 6.76±1.78 N cm. The mean values of ISQ for TRO-screws and COM-screws were 61.80±2.9 and 58.15±2.98. These indicated that TRO-screws were more stable than COM-screws. We found that the primary stability of the TRO-screw was better than that of the COM-screw.

MiR156/SQUAMOSA PROMOTER BINDING-LIKEs (SPLs) module is the key regulatory hub of juvenile-to-adult phase transition as a critical flowering regulator. In this study, a miR156-targeted PvSPL6 was identified and characterized in switchgrass (Panicum virgatum L.), a dual-purpose fodder and biofuel crop. Overexpression of PvSPL6 in switchgrass promoted flowering and reduced internode length, internode number, and plant height, whereas downregulation of PvSPL6 delayed flowering and increased internode length, internode number, and plant height. Protein subcellular localization analysis revealed that PvSPL6 localizes to both the plasma membrane and nucleus. We produced transgenic switchgrass plants that overexpressed a PvSPL6-GFP fusion gene, and callus were induced from inflorescences of selected PvSPL6-GFPOE transgenic lines. We found that the PvSPL6-GFP fusion protein accumulated mainly in the nucleus in callus and was present in both the plasma membrane and nucleus in regenerating callus. However, during subsequent development, the signal of the PvSPL6-GFP fusion protein was detected only in the nucleus in the roots and leaves of plantlets. In addition, PvSPL6 protein was rapidly transported from the nucleus to the plasma membrane after exogenous GA3 application, and returned from the plasma membrane to nucleus after treated with the GA3 inhibitor (paclobutrazol). Taken together, our results demonstrate that PvSPL6 is not only an important target that can be used to develop improved cultivars of forage and biofuel crops that show delayed flowering and high biomass yields, but also has the potential to regulate plant regeneration in response to GA3.

Clinical indicators do not adequately predict the long-term prognosis of patients with ST-segment elevation myocardial infarction (STEMI) following percutaneous coronary intervention (PCI). The low-density lipoprotein (LDL)/high-density lipoprotein (HDL) ratio is expected to be a reliable predictor of the long-term prognosis of these patients. This study aimed to explore the correlation between the LDL/HDL ratio and long-term prognosis in STEMI patients undergoing PCI. Patients with confirmed STEMI who underwent PCI in 7 hospitals in China from January 2009 to December 2011 were enrolled. Information about clinical endpoints, including all-cause death and major adverse cardiovascular events, was collected. Overall, 915 patients were included for analysis, the average follow-up time was 112.2 months. According to the LDL/HDL ratio, the patients were divided into 3 groups using the three-quantile method: low (LDL/HDL≤1.963), medium (1.963

Overuse of nitrogen fertilizer in fields has raised production costs, and caused environmental problems. Improving nitrogen use efficiency (NUE) of rice is essential for sustainable agriculture. Here we report the cloning, characterization and roles for rice of OsNPF7.6, a member of the nitrate transporter 1/peptide transporter family (NPF). The OsNPF7.6 protein is located in the plasma membrane, expressed in each tissue at all stages and is significantly regulated by nitrate in rice. Our study shows that the overexpression of OsNPF7.6 can increase the nitrate uptake rate of rice. Additionally, field experiments showed that OsNPF7.6 overexpression increased the total tiller number per plant and the grain weight per panicle, thereby improving grain yield and agronomic NUE in rice. Thus, OsNPF7.6 can be applied to be a novel target gene for breeding rice varieties with high NUE, and provide a reference for breeding higher yielding rice.

Fe–based metallic microwires possess unique microstructure and size effects, exhibiting favorable mechanical, electrical, and magnetic properties, thus distinguishing them as a possible agents for use as microwave absorbing materials. In this paper, the absorbing properties of Ni–doped Fe–based metallic microwires optimized by orthogonal experiments were investigated, and based on the optimal parameters, the influencing mechanism of the Ni doping amount on the absorbing properties was further analyzed. It was noted that at the frequency f = 8.36 GHz, the maximum reflection loss RL and electromagnetic wave absorption efficiency Aeff can reach −54.89 dB and 99.999%, respectively. Moreover, the Ni doping amount could result in the improved wave-absorbing properties of composites, obtain the corresponding optimal parameters, and even change the position of the maximum absorption peak, which are all of great significance for practical engineering applications.

This study synthesized the Forsythia@carbon quantum dots (CQDs) in one-pot method with a natural anti-wood rot fungus activity. Chinese herbal medicine-Forsythia was used as a raw material, and the environmental-friendly fluorescent Forsythia@CQDs was prepared through microwave treatment. The antifungal test against two fungi (G. trabeum, C. versicolor) demonstrated that the Minimum Inhibition Concentration (MIC) of Forsythia@CQDs was about 1% of the MIC of Forsythia suspense extract. The weight loss rate of wood samples treated by Forsythia@CQDs was as low as 1 (±0.5)%. The antifungal property was equivalent to that of the traditional chemical preservative Ammoniacal Copper Quats (ACQ). The leachability test results of wood preservatives showed that Forsythia@CQDs had a higher fixation rate in wood than Forsythia, and even exceeded ACQ preservatives. Also, its easily-detectable fluorescence effect could track the distribution of preservatives in the wood. This research indicates that Chinese herbal medicine@CQDs-derived environmentally-protective wood preservatives can be an improvement of standard chemical preservatives.

AbstractUsing genetic mutations to study protein functions in vivoSchizosaccharomyces pombein vivo

Mesocotyl is a crucial organ for pushing buds out of soil, which plays a vital role in seedling emergence and establishment in direct-seeded rice. Thus, the identification of quantitative trait loci (QTL) associated with mesocotyl length (ML) could accelerate genetic improvement of rice for direct seeding cultivation. In this study, QTL sequencing (QTL-seq) applied to 12 F2 populations identified 14 QTL for ML, which were distributed on chromosomes 1, 3, 4, 5, 6, 7, and 9 based on the Δ(SNP-index) or G-value statistics. Besides, a genome-wide association study (GWAS) using two diverse panels identified five unique QTL on chromosomes 1, 8, 9, and 12 (2), respectively, explaining 5.3–14.6% of the phenotypic variations. Among these QTL, seven were in the regions harboring known genes or QTLs, whereas the other 10 were potentially novel. Six of the QTL were stable across two or more populations. Eight high-confidence candidate genes related to ML were identified for the stable loci based on annotation and expression analyses. Association analysis revealed that two PCR gel-based markers for the loci co-located by QTL-seq and GWAS, Indel-Chr1:18932318 and Indel-Chr7:15404166 for loci qML1.3 and qML7.2 respectively, were significantly associated with ML in a collection of 140 accessions and could be used as breeder-friendly markers in further breeding.

Introduction Myelodysplastic syndromes (MDS) are a group of heterogeneous bone marrow clonal diseases characterized by the abnormal differentiation and development of bone marrow cells. Src homology region 2 domain-containing phosphatase (SHP)-1 is an important tumor suppressor gene that regulates the signal transducer and activator of transcription (STAT) pathway. Methods Survival analysis was performed to evaluate the function of decitabine (5-Aza) in treating MDS patients with and without SHP-1 methylation. The effects of 5-Aza treatment on SHP-1 expression and methylation and STAT3 phosphorylation were investigated in MDS cells by methylation-specific PCR, reverse transcription PCR, and western blotting. Cell viability and apoptosis were similarly evaluated by MTT assay and flow cytometry. Results High-risk MDS patients showed significant SHP-1 hypermethylation compared with low-risk patients, and patients with no SHP-1 methylation had longer overall survival. SHP-1 expression was significantly increased at mRNA and protein levels following 5-Aza treatment, while the phosphorylation of STAT3 protein was significantly decreased. Apoptosis increased significantly in MDS cells treated with higher doses of 5-Aza while cell viability decreased significantly. Conclusion SHP-1 hypermethylation was associated with poor prognosis in HR patients with MDS, suggesting it could be used as a prognostic indicator.

ABSTRACT Despite the availability of various osteoporosis treatments, adherence remains suboptimal. One contributing factor may be patient experience with therapy. This US, multicenter, combined retrospective chart review and patient questionnaire study included postmenopausal women at high risk for fracture and is the first study to describe real‐world patient experience with abaloparatide (ABL) injection. Eight geographically diverse secondary care sites in the United States participated (n = 193). Mean ± SD age was 67.4 ±8.62 years. Most patients (86%) were satisfied with the ABL regimen, especially with ease of preparation (82%), ease of storage (87%), and storage convenience (89%), an attribute 83% of the patients thought was important. The majority of patients reported complete satisfaction with the ABL regimen allowing for their ability to conduct daily activities (85%) and convenience to fit into their daily schedule (84%). All reported taking ABL as directed, by injection in the lower abdomen, and 83% of patients reported medium or high adherence. Patients were satisfied with the needle size (76% completely satisfied), and 93% reported never deliberately missing a dose. Although injecting medication (18%) and higher out‐of‐pocket costs (17%) were deemed the most bothersome attributes, the majority (69%) noted their healthcare team understands how osteoporosis impacts their lives. In multivariable analyses, ease of preparation (OR = 2.62; 95% CI, 1.01–6.81; p = 0.048) and fracture history (OR = 1.72; 95% CI, 1.03–2.86; p = 0.037) were significantly associated with overall satisfaction. Ease of preparation was a predictor of higher satisfaction with treatment convenience (coefficient = 13.60; 95% CI, 8.08–19.12; p = 0.00). Remembering to take the medication was a significant predictor of self‐reported adherence (OR = 16.66; 95% CI, 3.30–84.24; p = 0.001). In conclusion, the majority of patients were satisfied with ABL and found it convenient/easy to prepare and store. High self‐reported adherence may be associated with positive patient experience including ease of use and adequate support from healthcare providers. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

The number of osteoporosis-related fractures in the United States is no longer declining. Existing risk-based assessment tools focus on long-term risk. Payers and prescribers need additional tools to identify patients at risk for imminent fracture. We developed and validated a predictive model for secondary osteoporosis fractures in the year following an index fracture using administrative medical and pharmacy claims from the Optum Research Database and Symphony Health, PatientSource. Patients ≥50 years with a case-qualifying fracture identified using a validated claims-based algorithm were included. Logistic regression models were created with binary outcome of a second fracture versus no second fracture within a year of index fracture, with the goal of predicting second fracture occurrence. In the Optum Research Database, 197,104 patients were identified with a case-qualifying fracture (43% commercial, 57% Medicare Advantage). Using Symphony data, 1,852,818 met the inclusion/exclusion criteria. Average patient age was 70.09 (SD = 11.09) and 71.28 (SD = 14.24) years in the Optum Research Database and Symphony data, respectively. With the exception of history of falls (41.26% vs 18.74%) and opioid use (62.80% vs 46.78%), which were both higher in the Optum Research Database, the two populations were mostly comparable. A history of falls and steroid use, which were previously associated with increased fracture risk, continue to play an important role in secondary fractures. Conditions associated with bone health (liver disease), or those requiring medications that impact bone health (respiratory disease), and cardiovascular disease and stroke-which may share etiology or risk factors with osteoporosis fractures-were also predictors of imminent fractures. The model highlights the importance of assessment of patient characteristics beyond bone density, including patient comorbidities and concomitant medications associated with increased fall and fracture risk, in alignment with recently issued clinical guidelines for osteoporosis treatment.

ABSTRACT Type 2 diabetes mellitus (T2DM) increases fracture risk despite normal or increased BMD. Abaloparatide reduces fracture risk in patients with postmenopausal osteoporosis (PMO); however, its efficacy in women with T2DM is unknown. This post hoc analysis evaluated the efficacy and safety of abaloparatide in patients with T2DM. The analysis included patients with T2DM from the Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE), a phase 3, double‐blind, randomized, placebo‐ and active‐controlled trial. In ACTIVE, participants were randomized 1:1:1 to daily s.c. injections of placebo, abaloparatide (80 μg), or open‐label teriparatide (20 μg) for 18 months. A total of 198 women with PMO and T2DM from 21 centers in 10 countries were identified from ACTIVE through review of their medical records. The main outcomes measured included effect of abaloparatide versus placebo on BMD and trabecular bone score (TBS), with secondary outcomes of fracture risk and safety, in patients from ACTIVE with T2DM. Significant (p