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Seed vigor is a crucial indicator of seed quality. Variations in seed vigor are closely associated with seed properties and storage conditions. The vigor of mature seeds progressively declines during storage, which is called seed deterioration or aging. Seed aging induces a cascade of cellular damage, including impaired subcellular structures and macromolecules, such as lipids, proteins, and DNA. Reactive oxygen species (ROS) act as signaling molecules during seed aging causing oxidative damage and triggering programmed cell death (PCD). Mitochondria are the main site of ROS production and change morphology and function before other organelles during aging. The roles of other small redox-active molecules in regulating cell and seed vigor, such as nitric oxide (NO) and hydrogen sulfide (H 2 S), were identified later. ROS, NO, and H 2 S typically regulate protein function through post-translational modifications (PTMs), including carbonylation, S-glutathionylation, S-nitrosylation, and S-sulfhydration. These signaling molecules as well as the PTMs they induce interact to regulate cell fate and seed vigor. This review was conducted to describe the physiological changes and underlying molecular mechanisms that in seed aging and provides a comprehensive view of how ROS, NO, and H 2 S affect cell death and seed vigor., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: Meningeal lymphatic vessels (mLVs) have great potential to be the therapeutic target for β Amyloid protein (Aβ) clearing in Alzheimer's disease (AD), but the regulatory methods of the mLVs are limited. The lymphatic valve, marked by FOXC2, is the fundamental structure for maintaining stable lymphatic drainage function. Preliminary evidence suggested that borneol (BO) as the classical phytochemicals could enhance the expression of FOXC2 in the mLVs of healthy mice., Purpose: This study aims to explore the regulatory ability of BO on lymphatic valves of mLVs in the AD model mice., Study Design: We used the intracerebroventricular injection of Aβ42 oligomers to construct the AD-like symptoms model induced by toxic protein deposition. We administered BO nano micelles(BO-Ms) orally before and after to simulate the AD prevention and treatment strategy., Methods: Herein, this study characterized the efficacy and pathways of BO-Ms for regulating mLVs in AD model by Rt-PCR, WB and confocal microscopy, and determined the effects of BO-Ms on Aβ clearance, behavior and safety of AD mice., Results: The AD modeling process severely impaired the expression of lymphatic valves. However, after oral administering BO-Ms for prevention and treatment, an increase in the lymphatic valves of the transverse sinus was observed, which derived from the up-regulation of the transcription factor (FOXC2 and Akt) and the down-regulation of the transcription inhibitors (FOXO1 and PRDM1). Furthermore, the effects of BO-Ms on the lymphatic valves could enhance the lymphatic drainage of the mLVs in AD-like mice, promoting the clearance of toxicity aggregates, protecting neurons, and alleviating AD-like symptoms. Simultaneously, continuous oral BO-Ms for 30 days didn't show any significant organ toxicity. The most important thing was that the preventive effect of BO administration was superior to therapeutic administration in all data., Conclusion: In summary, our research indicated that BO is a promoter of lymphatic valve formation in the mLVs, and could prevent or repair damage caused by toxic Aβ42. BO was the only bioactive natural product with the ability to regulate mLVs valves. Thus, BO has the potential to become phytochemicals for alleviating AD symptoms by enhancing the drainage function of mLVs., Competing Interests: Declaration of competing interest The authors declared no potential conflicts of interest with respect to the research, author- ship, and/or publication of this article., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Drought and heat are major abiotic stresses frequently coinciding to threaten rice production. Despite hundreds of stress-related genes being identified, only a few have been confirmed to confer resistance to multiple stresses in crops. Here we report ONAC023, a hub stress regulator that integrates the regulations of both drought and heat tolerance in rice. ONAC023 positively regulates drought and heat tolerance at both seedling and reproductive stages. Notably, the functioning of ONAC023 is obliterated without stress treatment and can be triggered by drought and heat stresses at two layers. The expression of ONAC023 is induced in response to stress stimuli. We show that overexpressed ONAC23 is translocated to the nucleus under stress and evidence from protoplasts suggests that the dephosphorylation of the remorin protein OSREM1.5 can promote this translocation. Under drought or heat stress, the nuclear ONAC023 can target and promote the expression of diverse genes, such as OsPIP2;7, PGL3, OsFKBP20-1b, and OsSF3B1, which are involved in various processes including water transport, reactive oxygen species homeostasis, and alternative splicing. These results manifest that ONAC023 is fine-tuned to positively regulate drought and heat tolerance through the integration of multiple stress-responsive processes. Our findings provide not only an underlying connection between drought and heat responses, but also a promising candidate for engineering multi-stress-resilient rice., (© 2024. The Author(s).)

WRKY transcription factors play a central role in controlling plant organ senescence; however, it is unclear whether and how they regulate petal senescence in the widely grown ornamental plant tulip (Tulipa gesneriana). In this study, we report that TgWRKY75 promotes petal senescence by enhancing the synthesis of both abscisic acid (ABA) and salicylic acid (SA) in tulip and in transgenic Arabidopsis. The expression level of TgWRKY75 was up-regulated in senescent petals, and exogenous ABA or SA treatment induced its expression. The endogenous contents of ABA and SA significantly increased during petal senescence and in response to TgWRKY75 overexpression. Two SA synthesis-related genes, TgICS1 and TgPAL1, were identified as direct targets of TgWRKY75, which binds to their promoters. In parallel, TgWRKY75 activated the expression of the ABA biosynthesis-related gene TgNCED3 via directly binding to its promoter region. Site mutation of the W-box core motif located in the promoters of TgICS1, TgPAL1, and TgNCED3 eliminated their interactions with TgWRKY75. In summary, our study demonstrates a dual regulation of ABA and SA biosynthesis by TgWRKY75, revealing a synergistic process of tulip petal senescence through feedback regulation between TgWRKY75 and the accumulation of ABA and SA., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Drought stress significantly impacts global rice production, highlighting the critical need to understand the genetic basis of drought resistance in rice. Here, through a genome-wide association study, we reveal that natural variations in DROUGHT RESISTANCE GENE 9 (DRG9), encoding a double-stranded RNA (dsRNA) binding protein, contribute to drought resistance. Under drought stress, DRG9 condenses into stress granules (SGs) through liquid-liquid phase separation via a crucial α-helix. DRG9 recruits the mRNAs of OsNCED4, a key gene for the biosynthesis of abscisic acid, into SGs and protects them from degradation. In drought-resistant DRG9 allele, natural variations in the coding region, causing an amino acid substitution (G267F) within the zinc finger domain, increase DRG9's binding ability to OsNCED4 mRNA and enhance drought resistance. Introgression of the drought-resistant DRG9 allele into the elite rice Huanghuazhan significantly improves its drought resistance. Thus, our study underscores the role of a dsRNA-binding protein in drought resistance and its promising value in breeding drought-resistant rice., (© 2024. The Author(s).)

Herein, a novel biosorbent was successfully fabricated through a two-step process employing Pinus massoniana pollen as raw material. The efficacy of this biosorbent in eliminating methylene blue (MB), a typical organic cationic dye, from highly concentrated industrial wastewater was investigated. The results demonstrated that by adjusting the wettability of pollen microcarriers, it is possible to significantly increase their adsorption capacity for cationic dyes, resulting in a remarkable 25-fold improvement. The modified Pinus massoniana pollen microcarriers (MPPMC) exhibited an optimal adsorption capacity (585 mg/g) under specific conditions and a rapid equilibrium (97.6% in 5 min, uptake 487.8 mg/g) even at room temperature, showing excellent performance in removing MB efficiently and quickly. It is worth noting that the modified microcarriers could be regenerated via a simple pH-controlled adsorption-desorption cycle, maintaining their superior efficiency (> 99%) even after undergoing five cycles, indicating their excellent reproducibility. The MB adsorption process on MPPMC obeyed the pseudo-second-order kinetic model and followed the Langmuir model. Through the introduced modifications, the substantial deprotonation of carboxyl groups notably augmented electrostatic and hydrogen bonding interactions between MPPMC and MB. Overall, this study offers a sustainable, eco-friendly biological adsorbent, and the MPPMC exhibit the considerable potential for efficient and rapid removal of organic cationic dyes in wastewater., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: Diastasis recti abdominis (DRA) is a condition in which the linea alba is stretched and widened, and the abdominal muscles are separated from each other. DRA typically occurs in pregnant and postpartum women. We aimed to determine the risk factors and patient-reported outcomes (PROs) of DRA in Chinese postpartum women., Methods: This observational study was conducted in Hangzhou Hospital of Traditional Chinese Medicine, and involved 534 women who filled out the following risk-factor and PRO questionnaires: SF-MPQ-2, SF-ICIQ, LDQ, EPDS, MBIS, HerQles, and SF-36 (all Chinese versions). The inter-recti distance was measured by palpation. Statistical analyses were performed using SPSS v25.0 software and the Mann-Whitney U -test, chi-square test, binary logistic regression analysis (for risk factors of DRA), and the Kendall and Spearman tests (for correlation analysis)., Results: After childbirth, 78.1% (417/534) of the enrolled women had DRA. Abdominal surgery ( P = 0.002), number of pregnancies ( P = 0.035), parity ( P = 0.012), number of births ( P = 0.02), fetal birth weight ( P = 0.014), and waist-to-hip ratio in the supine position ( P = 0.045) significantly differed between the DRA and non-DRA groups. Caesarean delivery was an independent risk factor for DRA. The PROs were significantly worse in the DRA group than in the non-DRA group., Conclusion: Caesarean delivery was an independent risk factor for DRA. Women with DRA are more likely to have limited physical activity or function after childbirth, lower self-confidence, and a decreased quality of life., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Zhu et al.)

Gibberellins (GAs) play a pivotal role in modulating plant growth and development. Glucose-conjugated gibberellins (Glc-GAs), a prevalent conjugated form of GAs, regulate intracellular GA levels by the coupling and decoupling of glucose groups. However, the diversity of Glc-GAs identified within individual species remains limited, hinting at a multitude of yet undiscovered gibberellin metabolites. This lacuna poses considerable impediments to research efforts dedicated to comprehensively delineating the GA metabolic pathway. In this study, we developed a structure-oriented screening and identification method for Glc-GAs in plant species by employing LC-MS/MS coupled with chemical derivatization. Through the application of chemical derivatization technique, carboxyl groups on Glc-GAs were labeled which effectively enhanced the sensitivity and selectivity of mass spectrometry detection for these compounds. Concurrently, the integration of mass spectrometry fragmentation and chromatographic retention behavior facilitated the efficient screening and identification of potential Glc-GAs. With this strategy, we screened and identified 12 potential Glc-GAs from six plant species. These findings expand the Glc-GA diversity in plants and contribute to understanding GA metabolic pathways.

Matrix-variable optimization is a generalization of vector-variable optimization and has been found to have many important applications. To reduce computation time and storage requirement, this article presents two matrix-form recurrent neural networks (RNNs), one continuous-time model and another discrete-time model, for solving matrix-variable optimization problems with linear constraints. The two proposed matrix-form RNNs have low complexity and are suitable for parallel implementation in terms of matrix state space. The proposed continuous-time matrix-form RNN can significantly generalize existing continuous-time vector-form RNN. The proposed discrete-time matrix-form RNN can be effectively used in blind image restoration, where the storage requirement and computational cost are largely reduced. Theoretically, the two proposed matrix-form RNNs are guaranteed to be globally convergent to the optimal solution under mild conditions. Computed results show that the proposed matrix-form RNN-based algorithm is superior to related vector-form RNN and matrix-form RNN-based algorithms, in terms of computation time.

Odor emission from the soil of pesticide-contaminated sites is a prominent environmental problem in China, but there are very few researches about the component and spatial distribution of odorous substances in the soil of contaminated sites. In this paper, to investigate the odor pollution condition of an organophosphorus pesticide production site in a city of South China, the odor pollutants in the soil and soil gas were analyzed and the key odor-contributing substances were identified. Besides, the correlation between the concentrations of odorous substances in soil and soil gas was analyzed, and the measured results were compared with the predicted results by the linear model and DED model. An off-line soil gas sampling device was designed to collect the gas emitted from soil because the groundwater level in the site was too shallow to build a soil gas well. The key odor substances were screened from the detection results of soil gas via odor activity value (OAV) analysis, which revealed that the key odorous substances included benzene, ethylbenzene, ammonia, toluene, m,p-xylene, methyl sulfide, dimethyl disulfide, and formaldehyde. Furthermore, the spatial distribution of the odor substances in the soil of the pesticide-contaminated site was closely related to the layout and geologic structure of the site. The odor pollutants in soil were mainly distributed near the phosmet production workshop and the drainage ditch network. As for the deep distribution, the odorous substances were mainly enriched in the silty clay or clay layer (5.6-11 m), followed by the sludge layer (1-3.6 m). Finally, the predicted model (linear model and DED model) analysis suggested that the linear model was more suitable for predicting the concentration of odorous substances in the soil gas with the detection data of soil in this pesticide-contaminated site., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Docetaxel (DTX) is an artificial semi-synthetic second-generation taxane anti-tumor drug, which is suitable for the treatment of various cancers such as lung cancer. The route of administration of DTX formulations has been extended to oral, intravenous, and rectal, with few studies on pulmonary administration being reported. Here, we had developed DTX liposomes (DTX-lips) for pulmonary inhalation administration. The particle size of the preparation was 125 nm, the encapsulation efficiency was 94.4 ± 0.14%, and the drug loading capacity was 1.26 ± 0.01%. It had good stability. The fine particle fraction with aerodynamic diameter less than 6.4 μm accounts for 64.63 ± 0.12%, showed excellent aerosolization performance. DTX-lips were slow to release in simulated lung fluid. The fluorescence distribution experimented in mice and tissues showed that the fluorescence of the inhaled liposome group was mainly distributed in the lung, and the retention time was significantly prolonged as compared with those of the other two groups. No significant fluorescence was observed in other tissues, which was conducive to the full effect of the drug in the lung tissue. DTX-lips had no damage to respiratory system and whole body. These results indicated that the inhaled DTX-lips had good lung targeting, reduced accumulation in other organs, and improved the safety and effectiveness of the drug.

Introduction: Seeds are the most important carrier of germplasm preservation. However, an irreversible decrease in vigor can occur after the maturation of seeds, denoted as seed aging. Mitochondrion is a crucial organelle in initiation programmed cell death during seed aging. However, the underlying mechanism remains unclear., Methods: Our previous proteome study found that 13 mitochondria proteins underwent carbonylation modification during the aging of Ulmus pumila L. (Up) seeds. This study detected metal binding proteins through immobilized metal affinity chromatography (IMAC), indicating that metal binding proteins in mitochondria are the main targets of carbonization during seed aging. Biochemistry, molecular and cellular biology methods were adopted to detect metal-protein binding, protein modification and subcellular localization. Yeast and Arabidopsis were used to investigate the biological functions in vivo ., Results and Discussion: In IMAC assay, 12 proteins were identified as Fe 2 +/Cu 2 +/Zn 2 + binding proteins, including mitochondrial voltage dependent anion channels (VDAC). UpVDAC showed binding abilities to all the three metal ions. His204Ala (H204A) and H219A mutated UpVDAC proteins lost their metal binding ability, and became insensitive to metal-catalyzed oxidation (MCO) induced carbonylation. The overexpression of wild-type UpVDAC made yeast cells more sensitive to oxidative stress, retarded the growth of Arabidopsis seedlings and accelerated the seed aging, while overexpression of mutated UpVDAC weakened these effects of VDAC. These results reveal the relationship between the metal binding ability and carbonylation modification, as well as the probable function of VDAC in regulating cell vitality, seedling growth and seed aging., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Liu, Qi, Ye, Kang, Wang, Wang and Xue.)

After maturity, seed vigor irreversibly decreases. Understanding the underlying mechanism is important to germplasm preservation. MicroRNAs (miRNAs) play vital regulatory roles in plants. However, little is known about how miRNAs regulate seed aging. Here, elm ( Ulmus pumila L.) seeds of three aging stages were subjected to a multi-omics analysis including transcriptome, small RNAome and degradome, to find regulators of seed aging. In the small RNAome, 119 miRNAs were identified, including 111 conservative miRNAs and eight novel miRNAs specific to elm seeds, named upu-miRn1-8. A total of 4900 differentially expressed genes, 22 differentially expressed miRNAs, and 528 miRNA-target pairs were identified during seed ageing. The target genes were mainly involved in the processing of proteins in the endoplasmic reticulum, metabolism, plant hormone signal transduction, and spliceosome. The expression of several DEGs and miRNAs were verified by qRT-PCR. The degradome data showed the exact degradation sites of upu-miR399a on ABCG25 , and upu-miR414a on GIF1 , etc. The dual-luciferase assay verified the negative regulation of upu-miR399a on ABCG25 and upu-miR414a on GIF1 in tobacco leaves. This study outlined the regulation network of mRNA, miRNA and miRNA-target genes during seed aging, which is helpful in integrating the regulation mechanisms of seed vigor at the transcriptional and post-transcriptional levels.

Summary: HiCube is a lightweight web application for interactive visualization and exploration of diverse types of genomics data at multiscale resolutions. Especially, HiCube displays synchronized views of Hi-C contact maps and 3D genome structures with user-friendly annotation and configuration tools, thereby facilitating the study of 3D genome organization and function., Availability and Implementation: HiCube is implemented in Javascript and can be installed via NPM. The source code is freely available at GitHub (https://github.com/wmalab/HiCube)., (© The Author(s) 2023. Published by Oxford University Press.)

Rationale: The accumulation and clearance of amyloid-β (Aβ) peptides play a crucial role in the pathogenesis of Alzheimer's disease (AD). The (re)discovery of meningeal lymphatic vessels in recent years has focused attention on the lymphatic clearance of Aβ and has become a promising therapeutic target for such diseases. However, there is a lack of small molecular compounds that could clearly regulate meningeal lymphatic drainage to remove Aβ from the brain. Methods: We investigated the effect of borneol on meningeal lymphatic clearance of macromolecules with different molecular weights (including Aβ) in the brain. To further investigate the mechanism of borneol regulating meningeal lymphatic drainage, immunofluorescence staining, western blotting, ELISA, RT-qPCR, and Nitric Oxide assay kits were used. The cognitive function of AD mice after borneol treatment was evaluated using two behavioral tests: open field (OF) and Morris water maze (MWM). Results: This study discovered that borneol could accelerate the lymphatic clearance of Aβ from the brain by enhancing meningeal lymphatic drainage. Preliminary mechanism analysis revealed that borneol could improve the permeability and inner diameter of lymphatic vessels, allowing macromolecules to drain into the cervical lymph nodes (CLNS) and then be transported to the lymphatic circulation. To speed up the clearance of macromolecules, borneol also stimulated lymphatic constriction by lowering the level of nitric oxide in the meninges. In addition, borneol stimulated lymphangiogenesis by increasing the levels of FOXC2, VEGFC, and LYVE-1 in the meninges, which promoted the clearance rates of macromolecules. Borneol improved meningeal lymphatic clearance not only for Aβ but also for other macromolecular polymers (molecular weight in the range of 2 KD - 45 KD. Borneol ameliorated cognitive deficits and alleviated brain Aβ burden in Aβ-injected mice. Conclusions: Our findings not only provide a strategy to regulate lymphatic clearance pathways of macromolecules in the brain, but also new targets and ideas for treating neurodegenerative diseases like AD. Furthermore, our findings indicate that borneol is a promising therapeutic drug for AD., Competing Interests: Competing Interests: T.T.Y., Y.W., and S.J.W. are inventors on a patent related to this work (filed under number 202210358538.4). The other authors declare that they have no other competing interests., (© The author(s).)

Exudate management remains a major concern in slow or non-healing wound management. Therefore, there is a need to devise a massive exudate-absorbing, exudate-locking, and stable extracellular matrix structure-maintaining functional wound dressing. Inspired by metal-organic frameworks, we chemically introduced sandwich ferrocene (Fc) into hyaluronic acid (HA) to fabricate an innovative metal Fc-HA organic copolymer (FHoC) as the skeleton material for in situ gelation, which was then gently compressed into a pre-hydrogel patch (FHoCP). Fc promoted the rearrangement of polymer chains to form additional microcrystalline and hydrophobic regions, which improved hydrogel transition and the exudate-locking ability. Thus, the simple composition FHoCP(5) absorbed 150 times its weight of water and maintained a firm three-dimensional network, which contributed to reducing inflammation and acted as a physical barrier against hemostasis and anti-bacterial invasion. Meanwhile, multi-modal processes, including fibroblast migration, angiogenesis, and antibacterial effects, were integrated into the gelled FHoCP(5) guided by Fe to promote wound healing. This study suggested that FHoC biomaterial could accelerate the closure of chronic wounds. We believe that this unique FHoCP(5)-based in situ gelation strategy could provide a solid drug-loaded scaffold for cell or adjunctive drug therapies, which holds great potential for the development of multifunctional biomaterials. STATEMENT OF SIGNIFICANCE: Hydrogels that absorb excessive exudates while maintaining stable ECM-like network as well as exert multimodal wound healing activities are ideal dressings for accelerating chronic wound contraction. Herein, we reported an innovative metal ferrocene-hyaluronic acid organic copolymer patch (FHoCP) and FHoCP-mediated in situ gelation strategy. Ferrocene (Fc) induced in situ gelation by promoting polymer chain rearrangement, acting as a physical barrier for hemostasis and anti-bacterial invasion, and absorbing massive exudates, resulting in reducing delayed inflammation. As the structural core, rigid Fc enhanced the stability of the hydrogel backbone, and hydrophobic Fc improved fibroblast migration. In addition, Fe 2+ chemically inhibited bacteria and increased angiogenesis. These results indicated the potential of FHoCP-based hydrogel for application in clinical skin reconstruction., Competing Interests: Declaration of Competing Interest The authors reported no declarations of interest., (Copyright © 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Menthol, a cyclic terpene alcohol, plays a critical role in overcoming the blood-brain barrier and stratum corneum barrier. Herein, we innovatively propose a menthol nanoliposome (Men-nanoLips) that can dramatically increase lymph node accumulation of the dendritic cell (DC)-based anti-tumor vaccines. Specifically, Men-nanoLips efficiently enhanced lymphatic endothelial cell (EC) barrier permeability by reducing the expression of tight junction proteins. And interestingly, Men-nanoLips not only up-regulated the expression of CCR7 in DCs but also increased the secretion of CCL21 in lymphatic ECs. Moreover, Men-nanoLips promoted DC vaccine maturation as evidenced by increasing the expression of costimulatory molecules and up-regulating the pseudopodia-like protein. With those complementary mechanisms provided by Men-nanoLips, the number of the B16 whole-tumor cell lysate-loaded DCs that target the draining LN enhanced remarkably and significantly boosted the treatment efficacy of DC anti-tumor vaccines. Therefore, we concluded that Men-nanoLips could be instructive for increasing LN homing of DC vaccines., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflicts of interest regarding this article., (Copyright © 2022 Elsevier Inc. All rights reserved.)

To bear harsh environmental threats, plants have developed complex protection mechanisms involving phytohormones, counting abscisic acid (ABA). The function of the F-Box family containing the Domain of Unknown Function 295 (DUF295) has not yet been comprehensively characterized in Arabidopsis (Arabidopsis thaliana). In this study, we evaluated the function of a putative member of the F-Box/DUF295 family in Arabidopsis, F-box/DUF295 Brassiceae specific 2 (FDB2). We found that FDB2 expression was suppressed by ABA and abiotic stresses. FDB2 overexpression (OE) reduced ABA sensitivity during seed germination and seedling growth, but enhanced ABA-sensitivity of seed germination and seedling growth in fdb2 mutants was scored. When treated with ABA, expressions of ABI3, ABI4 and ABI5 showed decreased in OE lines but increased in fdb2 mutants. In addition, ABA-induced FDB2 degradation exhibited sensitive to MG132, suggesting that FDB2 degradation by ABA might be mediated by the ubiquitin-26S proteasome system. Moreover, ABA-induced significant over-accumulation of reactive oxygen species (ROS) at the root tips of fdb2 mutants was observed, this phenomenon was correlated to reduced activities of a set of ROS scavengers in fdb2 mutants relative to Col-0. In summary, our results suggest that Arabidopsis FDB2 is involved in ABA-mediated inhibition of seed germination, seedling growth including modulation of ROS homeostasis in roots., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Abscisic acid (ABA) hydroxylation is an important pathway for ABA inactivation and homeostasis maintenance. Here, we discover a new downstream catabolite of neophaseic acid (neoPA) in the ABA 9'-hydroxyl pathway and identify it as epi-neodihydrophaseic acid (epi-neoDPA) by comparing its accurate mass, retention time, and MS n spectra with those of our chemically synthesized epi-neoDPA. Analyses of Arabidopsis seed germination and ABA-related gene expression reveal that neoPA rather than epi-neoDPA possesses ABA-like hormonal activity. In vitro enzyme activity tests of prokaryotic recombinant protein reveal that NeoPAR1 (neoPA reductase 1) identified from Arabidopsis converts neoPA into epi-neoDPA. Site-directed mutation at Tyr163 in the conserved motif of NeoPAR1 abolishes the catalytic activity of NeoPAR1. Accelerated seed germination was observed in NeoPAR1 knockdown and knockout mutants, whereas retarded seed germination and the accumulation of epi-neoDPA and ABA were observed in NeoPAR1 overexpression lines, suggesting that NeoPAR1 is involved in seed germination and maintenance of ABA homeostasis., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to explore the impact of extreme precipitation on the risk of outpatient visits for depression and to further explore its associated disease burden and vulnerable population., Methods: A quasi-Poisson generalized linear regression model combined with distributed lag non-linear model (DLNM) was used to investigate the exposure-lag-response relationship between extreme precipitation (≥95th percentile) and depression outpatient visits from 2017 to 2019 in Suzhou city, Anhui Province, China., Results: Extreme precipitation was positively associated with the outpatient visits for depression. The effects of extreme precipitation on depression firstly appeared at lag4 [relative risk (RR): 1.047, 95% confidence interval (CI): 1.005-1.091] and lasted until lag7 (RR = 1.047, 95% CI: 1.009-1.087). Females, patients aged ≥65 years and patients with multiple outpatient visits appeared to be more sensitive to extreme precipitation. The attributable fraction (AF) and numbers (AN) of extreme precipitation on outpatient visits for depression were 5.00% (95% CI: 1.02-8.82%) and 1318.25, respectively., Conclusions: Our findings suggested that extreme precipitation may increase the risk of outpatient visits for depression. Further studies on the burden of depression found that females, aged ≥65 years, and patients with multiple visits were priority targets for future warnings. Active intervention measures against extreme precipitation events should be taken to reduce the risk of depression outpatient visits., (© 2022. The Author(s).)

Arsenic is known to be a notorious human carcinogen and rice consumption is becoming the primary human exposure route for As, especially in many Asian countries. As one of redox-sensitive elements in soil, sulfur plays an indisputable role in controlling As behaviors. However, information on the effects of persulfe (PS) on the toxicity and accumulation of As in rice plant under flooded conditions is limited. Therefore, a pot experiment was conducted to investigate the effects of PS amendment on the growth and accumulation of As species in rice plants grown in As-contaminated paddy soil. Results revealed that PS application increased the As, Fe, and Mn in porewater at the early stage, and then declined. Application of PS increased the biomass of stem and root, while inhibited the formation of iron plaque on the root surface. The As translocation from root to rice above tissues and accumulation of As species in brown rice were declined by amendment with PS. The inorganic arsenic (iAs) and DMA were the two main species in brown rice, and decreased by 13~26% and 40~60% respectively upon PS application. The results suggested that amendment with PS might be feasible for reducing the accumulation of As in rice grains grown in As-contaminated paddy soil. However, further detailed studies on the potential soil biogeochemical and physiological mechanisms are recommended., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In eukaryotic organisms, genetic information is usually carried on multiple chromosomes. Whether and how the number and configuration of chromosomes affect organismal fitness and speciation remain unclear. Here, we have successfully established several single-chromosome fission yeast Schizosaccharomyces pombe strains, in which the three natural chromosomes have been fused into one giant chromosome in different orders. Chromosome fusions accompanied by the deletions of telomeres and centromeres result in the loss of chromosomal interactions and a drastic change of global chromosome organization, but alter gene expression marginally. The single-chromosome strains display little defects in cell morphology, mitosis, genotoxin sensitivity, and meiosis. Crosses between a wild-type strain and a single-chromosome strain or between two single-chromosome strains with different fusion orders suffer defective meiosis and poor spore viability. We conclude that eukaryotic genomes are robust against dramatic chromosomal reconfiguration, and stochastic changes in chromosome number and genome organization during evolution underlie reproductive isolation and speciation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

In this study, a screening strategy was established based on ultrahigh-performance liquid chromatography coupled with high-resolution mass spectrometry assisted by chemical isotope labeling (CIL-UPLC-HRMS) for screening and identifying abscisic acid (ABA) catabolites. Based on the structures of known ABA catabolites, this strategy first proposed the structures of catabolites to be discovered. Afterward, a pair of isotope reagents N , N -2-dimethylaminoethylamine (DMED) and d 4 -DMED were used as labeling reagents to label the carboxyl groups in ABA and its catabolites. Then, the mass-to-charge ratio ( m / z ) of DMED- and d 4 -DMED-labeled ABA catabolites was calculated based on the labeling schema. In light of the characteristic fragmentation patterns of the DMED-labeled standards of ABA and its catabolites, screening criteria were formulated. Using our strategy, ABA, t- ABA, and 18 ABA catabolites were identified from seven plant samples. Of the identified catabolites, 16 were known, and to our knowledge, 2 were previously unidentified. Our findings contribute to ABA catabolic network improvement.

Rapid and large-scale estimation of soil salt content (SSC) and organic matter (SOM) using multi-source remote sensing is of great significance for the real-time monitoring of arable land quality. In this study, we simultaneously predicted SSC and SOM on arable land in the Yellow River Delta (YRD), based on ground measurement data, unmanned aerial vehicle (UAV) hyperspectral imagery, and Landsat-8 multispectral imagery. The reflectance averaging method was used to resample UAV hyperspectra to simulate the Landsat-8 OLI data (referred to as fitted multispectra). Correlation analyses and the multiple regression method were used to construct SSC and SOM hyperspectral/fitted multispectral estimation models. Then, the best SSC and SOM fitted multispectral estimation models based on UAV images were applied to a reflectance-corrected Landsat-8 image, and SSC and SOM distributions were obtained for the YRD. The estimation results revealed that moderately salinized arable land accounted for the largest proportion of area in the YRD (48.44%), with the SOM of most arable land (60.31%) at medium or lower levels. A significant negative spatial correlation was detected between SSC and SOM in most regions. This study integrates the advantages of UAV hyperspectral and satellite multispectral data, thereby realizing rapid and accurate estimation of SSC and SOM for a large-scale area, which is of great significance for the targeted improvement of arable land in the YRD.

Melatonin is known to involve multiple physiological actions in plants. Herein, we found that exogenous melatonin inhibited the Arabidopsis seedling growth through the elevated abscisic acid (ABA) levels, and the elevated ABA was ascribed to the upregulation of 9-cis-epoxycarotenoid dioxygenase genes (NCEDs) in the ABA biosynthesis pathway. We also found that the overexpression lines of the melatonin receptor gene PMTR1 (also known as Cand2) yielded smaller seeds and germinated slower than the wild type, whereas PMTR1-knockout mutants produced larger seeds and germinated faster than the wild type. During the seed development, the accumulation peak of ABA was higher in the PMTR1-knockout mutant, while it was lower in the PMTR1-overexpression line than that in the wild type. In the dry seeds and imbibed seeds, the PMTR1-overexpression line accumulated higher ABA levels, while the PMTR1-knockout contained less ABA than the wild type. In summary, our findings suggest that PMTR1 is involved in ABA-mediated seed development and germination in Arabidopsis., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Gasdermin E (GSDME) is one of the main members of the GSDM family and is originally involved in hereditary hearing loss. Recent studies have reported that GSDME expression is epigenetically silenced by methylation in several common tumours, thereby enhancing tumour proliferation and metastasis. GSDME is also downregulated in cancer tissues compared with normal tissues, which suggests that GSDME can be considered a tumour suppressor. Furthermore, GSDME is the effector protein of caspase-3 and granzyme B in pyroptosis, and it plays a significant role in innate immunity, tissue damage, cancer, and hearing loss, thus revealing potential novel therapeutic avenues. A great deal of evidence reveals that GSDME can be implemented as a biomarker in cancer diagnosis and monitoring, chemotherapy, immunotherapy, and chemoresistance. Based on the current knowledge of GSDME, this review is focussed on its mechanism of action and the most recent advances in its role in cancer and normal physiology., (Copyright © 2021. Published by Elsevier Inc.)

Phaseic acid (PA), a main catabolite of abscisic acid (ABA), is structurally related to ABA and possesses ABA-like hormonal activity. However, the comprehensive metabolism pathway and roles of PA are not well understood. Here, using homologous alignment and expression pattern analysis, we identified in Arabidopsis the previously named CRL1 (Cinnamoyl coA: NADP oxidoreductase-like 1) as a PA reductase that catalyses PA to dihydrophaseic acid. The function of CRL1 and the potential role of PA were studied in transgenic CRL1 plants. Overexpression of CRL1 resulted in decreased ABA sensitivity in seed germination and attenuated drought tolerance. In contrast, increased ABA sensitivity and elevated drought tolerance was observed in down-regulated and loss-of-function crl1 mutants. Tyr162 in the conserved motif is the key residue in CRL1 to catalyse PA. Accelerated seed germination and earlier flowering phenotype were also observed in overexpressing lines, while retarded seed germination and delayed flowering occurred in crl1 mutants which accumulated more PA, but less dihydrophaseic acid than the wild type. This study demonstrates that PA plays diverse functions in drought tolerance, seed germination and flowering in an ABA-like manner, which may increase the adaptive plasticity of plants., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Activation is an effective method to improve adsorption capacity of coal gangue, however, most activated gangues reported have limited adsorption capacity for phosphate because of the electronegativity, affecting their use in agricultural production and environmental protection. In order to enhance the phosphate absorption capacity of coal gangue through alkali-activation, three alkali-activated silicate coal gangue according to fine-size (AS-FCG 1 ), medium-size (AS-MCG 2 ), and large-size (AS-LCG 3 ) were prepared through grinding, calcining (800 °C) and stimulating with Ca(OH) 2 solution (0.1 M), and raw coal gangue (RCG 4 ) was used as control. The results revealed that AS-FCG has the best modified effects, its maximum phosphate adsorption capacity, according to Langmuir model, was 11.796 mg g -1 , which was 4.41, 8.16 and 73.73 times higher than that of AS-MCG, AS-LCG and RCG, respectively. The adsorption penetration time of AS-FCG packed column was over 30 h, which was longer than that of other samples. Besides, when the AS-FCG packed column loaded with phosphate was desorbed with distilled water, the phosphate concentration of filtrate was low and rapidly tended to 0 mg L -1 , while when it was desorbed with NaHCO 3 solution, the concentration remained high sustainably. The best adsorption performance of AS-FCG were associated with generation of calcium silicate hydrate gel and ettringite, which provided more Ca 2+ , Al 3+ , hydroxyl and larger specific surface area. It is suggested that alkali-activation is able to truly realize the recycling of solid waste, AS-FCG is an inexpensive, durable and eco-friendly material, which could not only be used to hold phosphate, but also release it slowly as fertilizer., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Meloxicam is an enolate nonsteroidal anti-inflammatory agent. This trial investigated the pharmacokinetics, safety, and bioequivalence of single oral doses of Aomei meloxicam (15 mg) and Mobic meloxicam (15 mg) in healthy volunteers under fasting and fed conditions. A single-site, single-dose, randomized, open, 2-period, 2-sequence, crossover bioequivalence study was performed: 24 healthy volunteers were enrolled in each of the fasting and fed arms. Each HV was randomly assigned to receive the Aomei drug (test) in one period and the Mobic drug (reference) in the other period. The concentration of meloxicam in plasma was detected using liquid chromatography-tandem mass spectrometry. The primary pharmacokinetic parameters were calculated using a noncompartmental model. In the fasting arm, the 90% confidence interval of the geometric mean ratios of maximum plasma concentration, area under the concentration-time curve from time 0 to the last measurable plasma concentration, and area under the concentration-time curve from time 0 to infinity between the test and reference products were 99.5% to 111.7%, 101.2% to 106.8%, and 101.8% to 108.3%, respectively. In the fed arm, the 3 parameters were 94.1% to 102.4%, 97.6% to 103.0%, and 97.5% to 103.7%, respectively. These parameters were in the range of 80% to 125%, and the 2 products were considered bioequivalent in both the fasting and fed states and were well tolerated. The severity of all adverse events was mild. Aomei meloxicam tablets and Mobic meloxicam tablets were bioequivalent in healthy Chinese volunteers., (© 2021, The American College of Clinical Pharmacology.)

Allisartan isoproxil (AI) is a blocker of the angiotensin II type 1 receptor. We evaluated the safety and pharmacokinetics of single- and multiple-dose AI in healthy Chinese individuals. Participants were assigned to receive AI or placebo. Plasma concentration of EXP3174 (carboxylic acid derivative) was measured using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were determined by noncompartmental methods. Twelve subjects were enrolled, and the ratio of men to women was 5:1. Main pharmacokinetic parameters of EXP3174 after single and multiple doses of AI were a mean maximum concentration in plasma (C max ) of 2242 ± 1037 ng/mL and median time to reach C max (T max ) of 3.5 hours (2.5-8 hours). The median T max, at steady state was 4.0 hours (1.5-8 hours). The mean C max at steady state (C max, SS ) was 2047 ± 1050 ng/mL. In terms of EXP3174, there was no significant difference in the C max, SS , area under the curve from time zero to 24 hours of quantifiable concentration at steady state (AUC 0-24 SS ), and AUC 0-72 after multiple doses of AI. Serious adverse events did not occur. These data suggest that AI is safe and well tolerated in healthy Chinese individuals at a single dose of 480 or 480 mg once daily for 7 days., (© 2021, The American College of Clinical Pharmacology.)

Background: Diastasis rectus abdominis (DRA) is one of the common complications during pregnancy and post-partum, which has psychological and physical effects on post-partum women. Acupuncture, a worldwide alternative therapy, has attracted wide attention in preventing and treating diseases related to pregnancy and childbirth. This study aims to evaluate the efficacy of acupuncture combined with physical training in treating post-partum rectus muscle dissociation. Methods: This is a randomized, controlled trial of DRA in post-partum conducted at Hangzhou Hospital of Traditional Chinese Medicine Affiliated with Zhejiang University of Chinese Medicine. The primary purpose is to evaluate the effectiveness of acupuncture and physical training on DRA in post-partum women. The study will be conducted from March 2022 to March 2023. The acupuncture group received acupuncture and physical training ( n = 48), the sham acupuncture group received sham acupuncture and physical training ( n = 48), and the physical training group received physical training ( n = 48). These experiments perform once/day, five times a week for 2 weeks, followed up for half a year after the end of the course of treatment. Our tests perform a course of treatment, which includes a total of 10 consecutive treatments. Furthermore, the patient will be followed up for half a year after the treatment. Primary and secondary indicators, including inter recti distance (IRD), linea alba (LA) tension, the MOS item short-form health survey (SF-36), short-form McGill pain questionnaire-2 (SF-MPQ-2), body mass index (BMI), waist-to-hip ratio (WHR), leeds dyspepsia questionnaire (LDQ), menstrual distress questionnaire (MDQ), 10 items of edinburgh post-natal depression scale (EPDS-10), the modified body self-image scale (MBIS), international consultation incontinence questionnaire short-form (ICIQ-SF) and hernia-related quality-of-life survey (HerQles), which will be evaluated before and after treatment and half a year after treatment. Adverse events and side effects during each treatment will be collected and recorded. Discussion: There is evidence that acupuncture and physical training can treat DRA in post-partum. In this study, we evaluate the effectiveness of acupuncture in post-partum with DRA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Zhu, Jiang, Lu, Xiao, Chen, Wang, Deng, Zhang, Shi, Zheng, Feng, Ye and Wang.)

Seed aging is the gradual decline in seed vigor, during which programmed cell death (PCD) occurs. The functions of nitric oxide (NO) are exerted through protein S-nitrosylation, a reversible post-translational modification. During seed aging, more than 80 proteins are S-nitrosylated, but the particular role of individual proteins is unknown. Here, we showed that the S-nitrosylation level of glyceraldehyde 3-phosphate dehydrogenase (UpGAPDH) in elm (Ulmus pumila L.) seeds increased after controlled deterioration treatment. UpGAPDH was S-nitrosylated at Cys154 during S-nitrosoglutathione (GSNO) treatment, and its oligomerization was triggered both in vitro and in elm seeds. Interestingly, UpGAPDH interacted with the mitochondrial voltage-dependent anion channel in an S-nitrosylation-dependent way. Some UpGAPDH-green fluorescent protein in Arabidopsis protoplasts co-localized with mitochondria during the GSNO treatment, while the S-nitrosylation-defective UpGAPDH C154S-GFP protein did not. Seeds of oxUpGAPDH lines showed cell death and lost seed vigor rapidly during controlled deterioration treatment-triggered seed aging, while those overexpressing S-nitrosylation-defective UpGAPDH-Cys154 did not. Our results suggest that S-nitrosylation of UpGAPDH may accelerate cell death and seed deterioration during controlled deterioration treatment. These results provide new insights into the effects of UpGAPDH S-nitrosylation on protein interactions and seed aging., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: An artificial intelligence (AI)-assisted contouring system benefits radiation oncologists by saving time and improving treatment accuracy. Yet, there is much hope and fear surrounding such technologies, and this fear can manifest as resistance from health care professionals, which can lead to the failure of AI projects., Objective: The objective of this study was to develop and test a model for investigating the factors that drive radiation oncologists' acceptance of AI contouring technology in a Chinese context., Methods: A model of AI-assisted contouring technology acceptance was developed based on the Unified Theory of Acceptance and Use of Technology (UTAUT) model by adding the variables of perceived risk and resistance that were proposed in this study. The model included 8 constructs with 29 questionnaire items. A total of 307 respondents completed the questionnaires. Structural equation modeling was conducted to evaluate the model's path effects, significance, and fitness., Results: The overall fitness indices for the model were evaluated and showed that the model was a good fit to the data. Behavioral intention was significantly affected by performance expectancy (β=.155; P=.01), social influence (β=.365; P<.001), and facilitating conditions (β=.459; P<.001). Effort expectancy (β=.055; P=.45), perceived risk (β=-.048; P=.35), and resistance bias (β=-.020; P=.63) did not significantly affect behavioral intention., Conclusions: The physicians' overall perceptions of an AI-assisted technology for radiation contouring were high. Technology resistance among Chinese radiation oncologists was low and not related to behavioral intention. Not all of the factors in the Venkatesh UTAUT model applied to AI technology adoption among physicians in a Chinese context., (©Huiwen Zhai, Xin Yang, Jiaolong Xue, Christopher Lavender, Tiantian Ye, Ji-Bin Li, Lanyang Xu, Li Lin, Weiwei Cao, Ying Sun. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 30.09.2021.)

Objectives: As a rare malformation of the female reproductive system, Herlyn-Werner-Wunderlich syndrome (HWWS) was categorized into 3 classifications. It was recommended recently that, on the basis of the past classification, cervicovaginal atresia without communicating uteri should be newly added as classification 4. The surgical intervention will differ by type. To better optimize patient counseling as well as the preoperative evaluation and planning, our objective was to describe the ultrasound characteristics of each type of HWWS, including the new type., Methods: From January 1995 to November 2015, 37 cases of HWWS in with complete ultrasound information confirmed by surgery in the Peking Union Medical College Hospital were reviewed. We analyzed their ultrasound features, including hematometra, hematocervix, hematocolpos, and an ovarian chocolate cyst., Results: All of the ultrasound images of the 37 patients showed uterus didelphys with ipsilateral renal agenesis. Compared with the other 3 types, classification 4 showed distinctive ultrasound characteristics. Most cases of classification 4 showed hematometra (5 of 7 [71.4%]) and an ipsilateral ovarian chocolate cyst (6 of 7 [85.7%]), which was significantly higher than in the other 3. A rudimentary uterine horn was also a distinctive characteristic in this type. Meanwhile none of the classification 4 cases showed hematocervix or hydrocolpos, which were common signs of the other 3., Conclusions: According to this new classification criteria for HWWS, ultrasound characteristics of the new classification 4 differ from the others. As classification 4 was suggested to have a different surgical option, we should pay attention to its ultrasound characteristics, which might help in providing more information about the treatment and prognosis to the gynecologist., (© 2020 American Institute of Ultrasound in Medicine.)

Fosaprepitant dimeglumine (FD) is a precursor of aprepitant. FD can be metabolized into aprepitant. This randomized, single-center, open, 2-cycle, single-dose, crossover bioequivalence study compared the pharmacokinetics (PK) and safety of intravenously FD of test and reference products in healthy volunteers (HVs). HVs were assigned to the test group or reference group randomly and given FD intravenously. The plasma concentration of FD and aprepitant was measured using liquid chromatography-tandem mass spectrometry. PK parameters were ascertained based on a noncompartmental model. Data for 29 HVs were obtained. The geometric mean and 90% confidence intervals of maximum plasma concentration (C max ), area under the concentration-time curve from time 0 to time of last measurable plasma concentration (AUC 0-t ), and area from the last datum point to time infinity (AUC 0-∞ ) of test and reference groups were 101.69% (95.06%, 108.77%), 103.52% (99.15%, 108.09%), and 105.58% (99.51%, 112.01%), respectively. These 3 parameters were within the acceptance range of 80.0% to 125.00%, and the test product was bioequivalent to the reference product. The coefficient of variation (CV) of C max , AUC 0-t , and AUC 0-∞ was 15.14%, 9.67%, and 11.89%, respectively. Intravenously administered FD provided by 2 sponsors achieved bioequivalence. FD values from test and reference products were bioequivalent. All adverse events were mild and serious adverse events absent in HVs. This study indicated that FD may provide a safer alternative to aprepitant for chemotherapy-induced nausea and vomiting., (© 2020, The American College of Clinical Pharmacology.)

Over the past five years, oxygen-based nanocarriers (NCs) to boost anti-tumor therapy attracted tremendous attention from basic research and clinical practice. Indeed, tumor hypoxia, caused by elevated proliferative activity and dysfunctional vasculature, is directly responsible for the less effectiveness or ineffective of many conventional therapeutic modalities. Undeniably, oxygen-generating NCs and oxygen-carrying NCs can increase oxygen concentration in the hypoxic area of tumors and have also been shown to have the ability to decrease the expression of drug efflux pumps (e.g., P-gp); to increase uptake by tumor cells; to facilitate the generation of cytotoxic reactive oxide species (ROS); and to evoke systematic anti-tumor immune responses. However, there are still many challenges and limitations that need to be further improved. In this review, we first discussed the mechanisms of tumor hypoxia and how it severely restricts the therapeutic efficacy of clinical treatments. Then an up-to-date account of recent progress in the fabrications of oxygen-generating NCs and oxygen-carrying NCs are systematically introduced. The improved physicochemical and surface properties of hypoxia alleviating NCs for increasing the targeting ability to hypoxic cells are also elaborated with special attention to the latest nano-technologies. Finally, the future directions of these NCs, especially towards clinical translation, are proposed. Therefore, we expect to provide some valued enlightenments and proposals in engineering more effective oxygen-based NCs in this promising field in this comprehensive overview., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Wu, Zhang, Bai, Ye and Wang.)

Gibberellins (GAs) play crucial roles in plant growth and development, and their regulatory functions rely on complex metabolic networks and signaling pathways. Therefore, the exploration of GAs metabolic network is of great importance. However, limited GAs have been found in given plant species, which makes it difficult to comprehensively study the GAs metabolic network. Herein, a structure-guided strategy for GAs screening based on liquid chromatography-mass spectrometry analysis assisted by chemical isotope labeling (CIL-LC-MS) was developed. In the proposed strategy, N,N-dimethyl ethylenediamine (DMED) and its isotopologue d 4 -DMED were used to label GAs. In light of the characteristic fragmentation patterns exhibited by the labeled GAs, four principles were summarized to screen the potential GAs from plant tissues. Subsequently, the MS/MS fragmentation behavior and quantitative structure-retention relationship (QSRR) model were employed to assist in deciphering structures of GA candidates. With this strategy, thirty potential GAs were screened out and identified from five plant species. Seven of them were confirmed by the authentic standards. Twenty-two of them have not been reported before in the five plant species used in this study, including thirteen that have been reported in other plant species and nine that have never been reported in any plant species. Noteworthily, a total of nine potential GAs were speculated to be novel 16, 17-double hydrated GAs, which indicated that the 16, 17-double hydration may be a ubiquitous metabolic pathway of GAs in plants. This study was the first attempt to establish a structure-guided screening strategy for GAs. Our findings have enriched the GA species in plants and expanded the GAs family, which may be helpful for study of the metabolic pathway and physiological function of GAs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Bermudagrass (Cynodon dactylon) is a widely used warm-season turfgrass species with superior stress tolerance except for cold. In this study, a comparative analysis of the responses to alkali stress in bermudagrass at the physiological and metabolomic levels were performed. Mild alkali with relatively low pH slightly inhibited growth of bermudagrass as evidenced by lower electrolyte leakage, more rapid growth and higher survival rate when compared to moderate and severe alkali treatments. Moreover, the amount of 37 metabolites including amino acids, organic acids, sugars and sugar alcohols were modulated by the alkali treatments. Among them, 15 metabolites were involved in carbon and amino acid metabolic pathways. Under mild alkali stress, bermudagrass possibly slowed down metabolisms to maintain basic growth. However, moderate and severe alkali-stressed plants accumulated significantly higher amount of carbohydrates which might result in carbon starvation. Taken together, alkali stress had severely inhibitory effect partially due to combined ionic stress and high pH stress. These results suggested that bermudagrass employed different strategies in response to alkali stresses with different pH and ionic values., (© 2020 Scandinavian Plant Physiology Society.)

Blind image deblurring has been a challenging issue due to the unknown blur and computation problem. Recently, the matrix-variable optimization method successfully demonstrates its potential advantages in computation. This paper proposes an effective matrix-variable optimization method for blind image deblurring. Blur kernel matrix is exactly decomposed by a direct SVD technique. The blur kernel and original image are well estimated by minimizing a matrix-variable optimization problem with blur kernel constraints. A matrix-type alternative iterative algorithm is proposed to solve the matrix-variable optimization problem. Finally, experimental results show that the proposed blind image deblurring method is much superior to the state-of-the-art blind image deblurring algorithms in terms of image quality and computation time.

The recently developed Hi-C technique has been widely applied to map genome-wide chromatin interactions. However, current methods for analyzing diploid Hi-C data cannot fully distinguish between homologous chromosomes. Consequently, the existing diploid Hi-C analyses are based on sparse and inaccurate allele-specific contact matrices, which might lead to incorrect modeling of diploid genome architecture. Here we present ASHIC, a hierarchical Bayesian framework to model allele-specific chromatin organizations in diploid genomes. We developed two models under the Bayesian framework: the Poisson-multinomial (ASHIC-PM) model and the zero-inflated Poisson-multinomial (ASHIC-ZIPM) model. The proposed ASHIC methods impute allele-specific contact maps from diploid Hi-C data and simultaneously infer allelic 3D structures. Through simulation studies, we demonstrated that ASHIC methods outperformed existing approaches, especially under low coverage and low SNP density conditions. Additionally, in the analyses of diploid Hi-C datasets in mouse and human, our ASHIC-ZIPM method produced fine-resolution diploid chromatin maps and 3D structures and provided insights into the allelic chromatin organizations and functions. To summarize, our work provides a statistically rigorous framework for investigating fine-scale allele-specific chromatin conformations. The ASHIC software is publicly available at https://github.com/wmalab/ASHIC., (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Loss of Hippo tumor-suppressor activity and hyperactivation of YAP are commonly observed in cancers. Inactivating mutations of Hippo kinases MST1/2 are uncommon, and it remains unclear how their activity is turned off during tumorigenesis. We identified STRN3 as an essential regulatory subunit of protein phosphatase 2A (PP2A) that recruits MST1/2 and promotes its dephosphorylation, which results in YAP activation. We also identified STRN3 upregulation in gastric cancer correlated with YAP activation and poor prognosis. Based on this mechanistic understanding and aided by structure-guided medicinal chemistry, we developed a highly selective peptide inhibitor, STRN3-derived Hippo-activating peptide, or SHAP, which disrupts the STRN3-PP2Aa interaction and reactivates the Hippo tumor suppressor, inhibits YAP activation, and has antitumor effects in vivo., Competing Interests: Declaration of Interests Z.Z., S.J., Y.T., G.F., W.W., and Y.Z. have filed a patent (CN111100189A) for the SHAP in China., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purposes: Parathyroid cancer (PC) is rare, but fatal condition. Preoperative prediction of PC remains challenging but meaningful. The aim of this study was to determine an effective model to predict PC in patients with parathyroid lesions >1.5 cm., Methods: In this retrospective case-control study, we enrolled 30 patients with PC matched to 60 patients with parathyroid adenoma or hyperplasia by admission year. All patients were diagnosed with primary hyperparathyroidism (pHPT) and had parathyroid lesions >1.5 cm. Ultrasonic features of the two patient groups, as well as demographic, clinical, and biochemical characteristics were retrospectively compared. Best subset selection and multivariate logistic regression analysis were conducted to identify the independent risk factors of PC. ROC curve and decision curve analysis were developed to evaluate the applicability of the new model., Results: The best subset selection method and multiple logistic regression analysis showed that ultrasonic features of DR (two diameters' ratio of the lesion) and tumor infiltration in conjunction with intact parathyroid hormone (iPTH) level (collective model) were independent predictors of malignancy. Meanwhile, DR, shape, and tumor infiltration (ultrasound model) were found to be risk factors when only ultrasonic features were included in the multivariate analysis. The decision curve analysis showed that collective model outperforms ultrasound model with a better net benefit and a wider range of threshold probabilities., Conclusions: Ultrasonic features in combination with iPTH level may be an applicable model for predicting PC and has a better potential to facilitate decision-making preoperatively.

Purpose: Testicular adrenal rests tumor (TART) is a rare kind of benign tumor in the testis. It usually occurred secondary to congenital adrenal hyperplasia (CAH), a hormonal disorder caused by hydroxylase deficiency. As the first-line examination method, ultrasound provides crucial diagnostic information for TART, although misdiagnosis to malignancy is quite common because of its rare prevalence. We aimed to summarize the sonographic manifestations of TART to improve the diagnostic accuracy and specificity., Methods: Eight CAH patients with TART identified by ultrasound in our medical center were retrospectively reviewed. Clinical and hormonal profile, semen analysis and treatment choices were collected. Sonographic examinations were performed at the first evaluation and interpreted by experienced radiologists individually. All patients received regular follow-up, and 5 patients undertook repeated scrotal ultrasound. A literature review of TART in CAH patients was conducted, with 123 patients from 23 articles since 1990 included., Results: A total of 8 patients aged between 4 to 27 years old were enrolled. 7 of 8 (87.5%) patients exhibited bilateral testicular lesions. The sizes of the testicular lesions were between 0.18 ml to 5.68 ml, and all showed a clear boundary. 10/15 (66.7%) lesions were homogenously hypoechoic, 4/15 (26.7%) were heterogeneously iso-hypoechoic, and 1/15 (6.7%) were homogenously isoechoic. 10/15 (66.7%) lesions were hyper-vascular. The longitudinal follow-up of 5 patients showed testicular lesions changed in terms of size, echogenicity, and vascularity after steroid treatment. A potential correlation may exist between ACTH levels and tumor size (p = 0.066). From the literature review, 100/123 (81%) patients got bilateral lesions, and 95% of them were located near the mediastinum. 80/103 (78%) lesions exhibited a clear boundary, and predominant lesions (74%) were hypoechogenic. Vascularity was with great diversity. Seventy-nine lesions of 44 patients were followed-up by scrotal ultrasound, among which 29 (37%) remained unchanged, 29(37%) shrank, and 21(27%) disappeared., Conclusions: Key sonographic characteristics of TART are: resembled lesions on both testes, located near the mediastinum, clear boundary, and changed in size or echogenicity after steroid treatment. These features can help radiologists to make an accurate diagnosis of TART.

Background: Poor quality primary health care is a major issue in China, particularly in blindness prevention. Artificial intelligence (AI) could provide early screening and accurate auxiliary diagnosis to improve primary care services and reduce unnecessary referrals, but the application of AI in medical settings is still an emerging field., Objective: This study aimed to investigate the general public's acceptance of ophthalmic AI devices, with reference to those already used in China, and the interrelated influencing factors that shape people's intention to use these devices., Methods: We proposed a model of ophthalmic AI acceptance based on technology acceptance theories and variables from other health care-related studies. The model was verified via a 32-item questionnaire with 7-point Likert scales completed by 474 respondents (nationally random sampled). Structural equation modeling was used to evaluate item and construct reliability and validity via a confirmatory factor analysis, and the model's path effects, significance, goodness of fit, and mediation and moderation effects were analyzed., Results: Standardized factor loadings of items were between 0.583 and 0.876. Composite reliability of 9 constructs ranged from 0.673 to 0.841. The discriminant validity of all constructs met the Fornell and Larcker criteria. Model fit indicators such as standardized root mean square residual (0.057), comparative fit index (0.915), and root mean squared error of approximation (0.049) demonstrated good fit. Intention to use (R 2 =0.515) is significantly affected by subjective norms (beta=.408; P<.001), perceived usefulness (beta=.336; P=.03), and resistance bias (beta=-.237; P=.02). Subjective norms and perceived behavior control had an indirect impact on intention to use through perceived usefulness and perceived ease of use. Eye health consciousness had an indirect positive effect on intention to use through perceived usefulness. Trust had a significant moderation effect (beta=-.095; P=.049) on the effect path of perceived usefulness to intention to use., Conclusions: The item, construct, and model indicators indicate reliable interpretation power and help explain the levels of public acceptance of ophthalmic AI devices in China. The influence of subjective norms can be linked to Confucian culture, collectivism, authoritarianism, and conformity mentality in China. Overall, the use of AI in diagnostics and clinical laboratory analysis is underdeveloped, and the Chinese public are generally mistrustful of medical staff and the Chinese medical system. Stakeholders such as doctors and AI suppliers should therefore avoid making misleading or over-exaggerated claims in the promotion of AI health care products., (©Tiantian Ye, Jiaolong Xue, Mingguang He, Jing Gu, Haotian Lin, Bin Xu, Yu Cheng. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 17.10.2019.)

The APETALA1 (AP1)/FRUITFULL (FUL)-like transcription factor OsMADS18 plays diverse functions in rice development, but the underlying molecular mechanisms are far from fully understood. Here, we report that down-regulation of OsMADS18 expression in RNAi lines caused a delay in seed germination and young seedling growth, whereas the overexpression of OsMADS18 produced plants with fewer tillers. In targeted OsMADS18 genome-edited mutants (osmads18-cas9), an increased number of tillers, altered panicle size, and reduced seed setting were observed. The EYFP-OsMADS18 (full-length) protein was localized to the nucleus and plasma membrane but the EYFP-OsMADS18-N (N-terminus) protein mainly localized to the nucleus. The expression of OsMADS18 could be stimulated by abscisic acid (ABA), and ABA stimulation triggered the cleavage of HA-OsMADS18 and the translocation of OsMADS18 from the plasma membrane to the nucleus. The inhibitory effect of ABA on seedling growth was less effective in the OsMADS18-overexpressing plants. The expression of a set of ABA-responsive genes was significantly reduced in the overexpressing plants. The phenotypes of transgenic plants expressing EYFP-OsMADS18-N resembled those observed in the osmads18-cas9 mutants. Analysis of the interaction of OsMADS18 with OsMADS14, OsMADS15, and OsMADS57 strongly suggests an essential role for OsMADS18 in rice development., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

Background: The invasive method for intracranial pressure measurement is 'gold standard' but not always feasible because the intraventricular catheter/ intraparenchymal micro transducer used in the measurement of intracranial pressure measurement may cause complications. Imaging modalities with clinical examination protocol have a lack of specificity and accuracy. The objective of the study was to compare the accuracy of diagnostic parameters of ultrasound measurements in patients with brain injury underwent invasive intracranial pressure measurement method., Methods: Data of invasive intracranial pressure measurement method and ultrasound measurements of 185 patients with brain injury who required admission diagnosis were included in the analysis. Pearson correlation was tested for diagnostic parameters. Logistical regression analysis was performed for diagnostic parameters of death patients to evaluate independent parameter of mortality., Results: Straight sinus flow velocities, middle cerebral artery flow velocities, and optic nerve sheath diameter were correlated with intracranial pressure (p < 0.0001 for all). Arterial blood pressure (p = 0.127) and middle cerebral artery pulsatility index (p = 0.06) were not correlated with intracranial pressure. A total of 47 patients died during the study period. Intracranial pressure (p = 0.015) and optic nerve sheath diameter (p = 0.035) were found to be independent predictor of mortality., Conclusions: Ultrasound measurement especially optic nerve sheath diameter can be successfully used instead of invasive intracranial pressure measurement method in patients with brain injury., Level of Evidence: III.

The objective of this study was to determine whether endophytic fungi, isolated from Kadsura angustifolia produce nigranoic acid and its highly oxygenated derivatives. From the 426 endophytic fungi screened, Trichoderma harzianum SWUKD3.1610 was detected to have a component with the same TLC R f value and HPLC retention time as authentic nigranoic acid. This component was further confirmed as nigranoic acid by investigating the chemical composition of the fungal extracts. Besides ( 1 ), one new triterpenoid, 7 β - schinalactone C ( 2 ), and two known minor compounds were isolated and characterized by HRESIMS, 1D and 2D NMR spectroscopic methods. Our study indicates that endophytic fungus may play an important role in increasing the quality of the crude drugs from Chinese medicinal plant K. angustifolia . This study is the first to isolate, characterize, and identify schitriterpenes-producing Trichoderma spp .

Nine phosphatidylinositol-specific phospholipases C (PLCs) have been identified in the Arabidopsis genome; among the importance of PLC2 in reproductive development is significant. However, the role of PLC2 in vegetative development such as in root growth is elusive. Here, we report that plc2 mutants displayed multiple auxin-defective phenotypes in root development, including short primary root, impaired root gravitropism, and inhibited root hair growth. The DR5:GUS expression and the endogenous indole-3-acetic acid (IAA) content, as well as the responses of a set of auxin-related genes to exogenous IAA treatment, were all decreased in plc2 seedlings, suggesting the influence of PLC2 on auxin accumulation and signalling. The root elongation of plc2 mutants was less sensitive to the high concentration of exogenous auxins, and the application of 1-naphthaleneacetic acid or the auxin transport inhibitor N-1-naphthylphthalamic acid could rescue the root hair growth of plc2 mutants. In addition, the PIN2 polarity and cycling in plc2 root epidermis cells were altered. These results demonstrate a critical role of PLC2 in auxin-mediated root development in Arabidopsis, in which PLC2 influences the polar distribution of PIN2., (© 2018 John Wiley & Sons Ltd.)