Genome-wide transcriptome analysis reveals key regulatory networks and genes involved in the determination of seed hardness in vegetable soybean.

Seed hardness is an important quality trait of vegetable soybean. To determine the factors underlying seed hardness, two landraces with contrasting seed hardness, Niumaohuang (low seed hardness) and Pixiansilicao (high seed hardness), were selected from 216 soybean accessions originating from 26 provinces in China. The contents of the main components in vegetable soybean seeds such as water, soluble sugar, starch, protein and oil were measured, and transcriptome analyses performed during five stages of seed developmental. Transcriptome analysis indicates that during the middle and late stages of seed development, a large number of genes involved in the synthesis or degradation of starch, storage protein, and fatty acids were differentially expressed, leading to differences in the accumulation of stored substances during seed maturation among Niumaohuang and Pixiansilicao. The activity of cell proliferation and the formation of cell walls in the middle and late stages of seed development may also affect the hardness of seeds to a certain extent. In addition, weighted gene co-expression network analysis (WGCNA) was undertaken to identify co-expressed gene modules and hub genes that regulate seed hardness. Overexpression of a candidate seed hardness regulatory hub gene, GmSWEET2, resulted in increased seed hardness. In this study, the important role of GmSWEET2 in regulating the hardness of vegetable soybean seeds was verified and numerous potential key regulators controlling seed hardness and the proportion of seed components were identified, laying the groundwork for improving the texture of vegetable soybean.

Poly-l-lysine modified MOF nanoparticles with pH/ROS sensitive CIP release and CUR triggered photodynamic therapy against drug-resistant bacterial infection.

The challenge of drug resistance in bacteria caused by the over use of biotics is increasing during the therapy process, which has attracted great attentions of the clinicians and scientists around the world. Recently, photodynamic therapy (PDT) triggered by photosensitizer (PS) has become a promising treatment method because of its high efficacy, easy operation, and low side effect. Herein, the poly-l-lysine (PLL) modified metal-organic framework (MOF) nanoparticles, ZIF/PLL-CIP/CUR, were synthesized to allow both reactive oxygen species (ROS) responsive drug release and photodynamic effect for synergistic therapy against drug resistant bacterial infections. The PLL was modified on the shell of the zeolite imidazole framework (ZIF) by the ROS-responsive thioketal linker for controllable CIP release. CUR were encapsulated in ZIF as the photosensitizer for blue light mediated photodynamic effect to produce singlet oxygen (1O2) and superoxide anion radical (O2-) for efficient inhibition towards methicillin-resistant Staphylococcus aureus (MRSA). The charge conversion from negative charge (-4.6 mV) to positive charge (2.6 mV) was observed at pH 7.4 and pH 5.5, and 70.9 % CIP was found released at pH 5.5 in the presence of H2O2, which suggests the good biosafety at physiological pH and ROS-responsive drug release of the as-prepared nanoparticle in the bacterial microenvironment. The as-prepared nanoparticles could effectively kill MRSA and disrupt bacterial biofilm by combination of chemo- and photodynamic therapy. In mice model, the as-prepared nanoparticles exhibited excellent biosafety and synergistic effect with 98.81 % healing rate in treatment of MRSA infection, which is considered as a promising candidate in combating drug resistant bacterial infection.

The role of ncRNAs in depression.

Depressive disorders have a significant impact on public health, and depression have an unsatisfactory recurrence rate and are challenging to treat. Non-coding RNAs (ncRNAs) are RNAs that do not code protein, which have been shown to be crucial for transcriptional regulation. NcRNAs are important to the onset, progress and treatment of depression because they regulate various physiological functions. This makes them distinctively useful as biomarkers for diagnosing and tracking responses to therapy among individuals with depression. It is important to seek out and summarize the research findings on the impact of ncRNAs on depression since significant advancements have been made in this area recently. Hence, we methodically outlined the findings of published researches on ncRNAs and depression, focusing on microRNAs. Above all, this review aims to improve our understanding of ncRNAs and provide new insights of the diagnosis and treatment of depression.

Regulation of the MCHergic Neural Circuit to Dorsal Raphe Nucleus on Emotion-Related Behaviors and Intestinal Dysfunction in Mice Model of Irritable Bowel Syndrome with Diarrhea.

INTRODUCTION: Irritable bowel syndrome with diarrhea (IBS-D) is frequently accompanied by depression and anxiety, resulting in a reduced quality of life and increased medical expenditures. Although psychological factors are known to play an important role in the genesis and development of IBS-D, an understanding of the central neural control of intestinal dysfunction remains elusive. Melanin-concentrating hormone (MCH) is a gut-brain peptide involved in regulating feeding, sleep-wake rhythms, and emotional states. METHODS: This study investigated the regulation of the MCHergic neural circuit from the lateral hypothalamic area (LHA) to the dorsal raphe nucleus (DRN) on anxiety- and depression-like behaviors, intestinal motility, and visceral hypersensitivity in a mice model of IBS-D. The models of IBS-D were prepared by inducing chronic unpredictable mild stress (CUMS). RESULTS: Chemogenetic activation of the MCH neurons in the LHA could excite serotonin (5-HT) neurons in the DRN and induce anxiety- and depression-like behaviors and IBS-D-like symptoms, which could be recovered by microinjection of the MCH receptor antagonist SNAP94847 into the DRN. The mice model of IBS-D showed a reduction of 5-HT and brain-derived neurotrophic factor (BDNF) expression in the DRN, while an elevation of 5-HT and BDNF was observed in the colon through immunofluorescent staining, ELISA, and western blot analysis. SNAP94847 treatment in the DRN alleviated anxiety- and depression-like behaviors, improved intestinal motility, and alleviated visceral hypersensitivity responses by normalizing the 5-HT and BDNF expression in the DRN and colon. CONCLUSION: This study suggests that the activation of MCH neurons in the LHA may induce IBS-D symptoms via the DRN and that the MCH receptor antagonist could potentially have therapeutic effects.

Broadening horizons: ferroptosis as a new target for traumatic brain injury.

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide, with ~50 million people experiencing TBI each year. Ferroptosis, a form of regulated cell death triggered by iron ion-catalyzed and reactive oxygen species-induced lipid peroxidation, has been identified as a potential contributor to traumatic central nervous system conditions, suggesting its involvement in the pathogenesis of TBI. Alterations in iron metabolism play a crucial role in secondary injury following TBI. This study aimed to explore the role of ferroptosis in TBI, focusing on iron metabolism disorders, lipid metabolism disorders and the regulatory axis of system Xc-/glutathione/glutathione peroxidase 4 in TBI. Additionally, we examined the involvement of ferroptosis in the chronic TBI stage. Based on these findings, we discuss potential therapeutic interventions targeting ferroptosis after TBI. In conclusion, this review provides novel insights into the pathology of TBI and proposes potential therapeutic targets.

A pilot study on the expression of circadian clock genes in the alveolar bone of mice with periodontitis.

This study aimed to investigate the expression of circadian clock genes in mouse alveolar bone, and the possible reasons for these changes. Fifty C57 mice were orally inoculated with P. gingivalis, establishing a model of periodontitis using healthy mice as controls. The alveolar bone of both groups was taken for micro-computed tomography scanning to measure the amount of attachment loss, and the relative expression of mRNA in each clock gene and periodontitis related inflammatory factor was detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). After the establishment of the mouse model, the height of alveolar bone in the periodontitis group was significantly lower than that in the normal group (p < 0.05). The relative transcriptional level of Bmal1, Per2, and Cry1 mRNA was in the circadian rhythm in the normal group (p ≤ 0.05), while in the periodontitis group, its circadian rhythm disappeared and the transcriptional level characteristics were changed. Interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and interferon (IFN-γ) mRNA transcriptional level were elevated in the periodontitis group compared to the normal group. In conclusion, the mRNA transcriptional level of Bmal1, Per2, and Cry1 in alveolar bone of normal mice has circadian rhythm, but the rhythm disappears under the condition of periodontitis, and the cause of its occurrence may be related to inflammatory cytokines.

Self-assembled soft alloy with Frank-Kasper phases beyond metals.

Soft building blocks, such as micelles, cells or soap bubbles, tend to adopt near-spherical geometry when densely packed together. As a result, their packing structures do not extend beyond those discovered in metallic glasses, quasicrystals and crystals. Here we report the emergence of two Frank-Kasper phases from the self-assembly of five-fold symmetric molecular pentagons. The µ phase, an important intermediate in superalloys, is indexed in soft matter, whereas the ϕ phase exhibits a structure distinct from known Frank-Kasper phases in metallic systems. We find a broad size and shape distribution of self-assembled mesoatoms formed by molecular pentagons while approaching equilibrium that contribute to the unique packing structures. This work provides insight into the manipulation of soft building blocks that deviate from the typical spherical geometry and opens avenues for the fabrication of 'soft alloy' structures that were previously unattainable in metal alloys.

Targeting ferroptosis and ferritinophagy: new targets for cardiovascular diseases. / 靶向铁死亡和铁自噬： å¿ƒè¡€ç®¡ç–¾ç— çš„æ–°é¶ç‚¹ï¼Ÿ.

Cardiovascular diseases (CVDs) are a leading factor driving mortality worldwide. Iron, an essential trace mineral, is important in numerous biological processes, and its role in CVDs has raised broad discussion for decades. Iron-mediated cell death, namely ferroptosis, has attracted much attention due to its critical role in cardiomyocyte damage and CVDs. Furthermore, ferritinophagy is the upstream mechanism that induces ferroptosis, and is closely related to CVDs. This review aims to delineate the processes and mechanisms of ferroptosis and ferritinophagy, and the regulatory pathways and molecular targets involved in ferritinophagy, and to determine their roles in CVDs. Furthermore, we discuss the possibility of targeting ferritinophagy-induced ferroptosis modulators for treating CVDs. Collectively, this review offers some new insights into the pathology of CVDs and identifies possible therapeutic targets.

Regulated necrosis pathways: a potential target for ischemic stroke.

Globally, ischemic stroke causes millions of deaths per year. The outcomes of ischemic stroke are largely determined by the amount of ischemia-related and reperfusion-related neuronal death in the infarct region. In the infarct region, cell injuries follow either the regulated pathway involving precise signaling cascades, such as apoptosis and autophagy, or the nonregulated pathway, which is uncontrolled by any molecularly defined effector mechanisms such as necrosis. However, numerous studies have recently found that a certain type of necrosis can be regulated and potentially modified by drugs and is nonapoptotic; this type of necrosis is referred to as regulated necrosis. Depending on the signaling pathway, various elements of regulated necrosis contribute to the development of ischemic stroke, such as necroptosis, pyroptosis, ferroptosis, pathanatos, mitochondrial permeability transition pore-mediated necrosis and oncosis. In this review, we aim to summarize the underlying molecular mechanisms of regulated necrosis in ischemic stroke and explore the crosstalk and interplay among the diverse types of regulated necrosis. We believe that targeting these regulated necrosis pathways both pharmacologically and genetically in ischemia-induced neuronal death and protection could be an efficient strategy to increase neuronal survival and regeneration in ischemic stroke.

Transcription Factor GmERF105 Negatively Regulates Salt Stress Tolerance in Arabidopsis thaliana.

The Ethylene Response Factor (ERF) transcription factors form a subfamily of the AP2/ERF family that is instrumental in mediating plant responses to diverse abiotic stressors. Herein, we present the isolation and characterization of the GmERF105 gene from Williams 82 (W82), which is rapidly induced by salt, drought, and abscisic acid (ABA) treatments in soybean. The GmERF105 protein contains an AP2 domain and localizes to the nucleus. GmERF105 was selectively bound to GCC-box by gel migration experiments. Under salt stress, overexpression of GmERF105 in Arabidopsis significantly reduced seed germination rate, fresh weight, and antioxidant enzyme activity; meanwhile, sodium ion content, malonic dialdehyde (MDA) content, and reactive oxygen species (ROS) levels were markedly elevated compared to the wild type. It was further found that the transcription levels of CSD1 and CDS2 of two SOD genes were reduced in OE lines. Furthermore, the GmERF105 transgenic plants displayed suppressed expression of stress response marker genes, including KIN1, LEA14, NCED3, RD29A, and COR15A/B, under salt treatment. Our findings suggest that GmERF105 can act as a negative regulator in plant salt tolerance pathways by affecting ROS scavenging systems and the transcription of stress response marker genes.

A Thiol-Michael Approach Towards Versatile Functionalized Cyclic Titanium-Oxo Clusters.

In expanding our research activities of superlattice engineering, designing new giant molecules is the necessary first step. One attempt is to use inorganic transition metal clusters as building blocks. Efficient functionalization of chemically precise transition metal clusters, however, remains a great challenge to material scientists. Herein, we report an efficient thiol-Michael addition approach for the modifications of cyclic titanium-oxo cluster (CTOC). Several advantages, including high efficiency, mild reaction condition, capability of complete addition, high atom economy, as well as high functional group tolerance were demonstrated. This approach can afford high yields of fully functionalized CTOCs, which provides a powerful platform for achieving versatile functionalization of precise transition metal clusters and further applications.

Pressure and temperature effects on the Raman spectra of LLM-105.

Currently, only one crystal structure of LLM-105 (2,6-diamino-3,5-dinitropyrazine-1-oxide) (P21/n) has been discovered, and there are still debates on its phase transition point and phase diagram. Based on previous work, we performed crystal structure, Raman spectra, and vibrational properties calculations on LLM-105 crystal. Our results indicate that the crystal structure of LLM-105 remains stable until compressed to 49 GPa, beyond which it may undergo two phase transitions at pressure intervals of 49.0-49.1 GPa and 51.4-51.5 GPa, respectively. Analysis of Raman shift results suggests that these two phase transitions may be reversible, with an intermediate phase possibly acting as a transition phase. Additionally, based on the quasi-harmonic approximation, we fitted the experimental data of LLM-105 lattice expansion state, obtaining the volume at zero pressure and using it for Raman spectra calculations. The results demonstrated the accuracy of this quasi-harmonic approximation method in describing the redshift of Raman peaks during the heating process and the excitation ratio of Raman peaks in different wavenumber ranges.

The microglial innate immune receptors TREM-1 and TREM-2 in the anterior cingulate cortex (ACC) drive visceral hypersensitivity and depressive-like behaviors following DSS-induced colitis.

Inflammatory bowel disease (IBD) is a chronic condition with a high recurrence rate. To date, the clinical treatment of IBD mainly focuses on inflammation and gastrointestinal symptoms while ignoring the accompanying visceral pain, anxiety, depression, and other emotional symptoms. Evidence is accumulating that bi-directional communication between the gut and the brain is indispensable in the pathophysiology of IBD and its comorbidities. Increasing efforts have been focused on elucidating the central immune mechanisms in visceral hypersensitivity and depression following colitis. The triggering receptors expressed on myeloid cells-1/2 (TREM-1/2) are newly identified receptors that can be expressed on microglia. In particular, TREM-1 acts as an immune and inflammatory response amplifier, while TREM-2 may function as a molecule with a putative antagonist role to TREM-1. In the present study, using the dextran sulfate sodium (DSS)-induced colitis model, we found that peripheral inflammation induced microglial and glutamatergic neuronal activation in the anterior cingulate cortex (ACC). Microglial ablation mitigated visceral hypersensitivity in the inflammation phase rather than in the remission phase, subsequently preventing the emergence of depressive-like behaviors in the remission phase. Moreover, a further mechanistic study revealed that overexpression of TREM-1 and TREM-2 remarkably aggravated DSS-induced neuropathology. The improved outcome was achieved by modifying the balance of TREM-1 and TREM-2 via genetic and pharmacological means. Specifically, a deficiency of TREM-1 attenuated visceral hyperpathia in the inflammatory phase, and a TREM-2 deficiency improved depression-like symptoms in the remission phase. Taken together, our findings provide insights into mechanism-based therapy for inflammatory disorders and establish that microglial innate immune receptors TREM-1 and TREM-2 may represent a therapeutic target for the treatment of pain and psychological comorbidities associated with chronic inflammatory diseases by modulating neuroinflammatory responses.

Multicenter Population Pharmacokinetics and Exposure-Efficacy Analysis of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis.

BACKGROUND AND OBJECTIVE: Pirfenidone is an antifibrotic agent that has been proven to slow down the progression of idiopathic pulmonary fibrosis (IPF). This study aimed to characterize the population pharmacokinetics (PK) and exposure-efficacy analysis of pirfenidone in patients with IPF. METHODS: Data from 10 hospitals with 106 patients were used to develop a population PK model. The annual decline in forced vital capacity (FVC) over 52 weeks was integrated with pirfenidone plasma concentration to characterize the exposure-efficacy relationship. RESULTS: A linear one-compartment model with first-order absorption and elimination processes and lag time best described the pirfenidone PK. The population estimates of clearance and central volume of distribution at steady-state were 13.37 L/h and 53.62 L, respectively. Bodyweight and food were statistically correlated with PK variability but had no significant influence on pirfenidone exposure. Annual decline in FVC with pirfenidone plasma concentration was described by a maximum drug effect (Emax) model. The typical EC50 was 1.73 mg/L (1.18-2.31 mg/L) and the corresponding EC80 was 2.18 mg/L (1.49-2.87 mg/L). Simulations showed that two dosing regimens of 500 and 600 mg three times daily were predicted to generate 80% of the Emax. CONCLUSIONS: In patients with IPF, covariates such as bodyweight and food might not be sufficient for dose adjustment, and a low dose of 1500 mg/day could also provide 80% of the Emax, as the standard dose (1800 mg/day).

Pharmacokinetic study of Strongylocentrotus nudus egg polysaccharide in rats and beagles using a 3H-labeling method.

Strongylocentrotus nudus egg polysaccharide (SEP) extracted from sea urchins has potential anticancer activity. However, little is known about its pharmacokinetic properties. To investigate the pharmacokinetics of SEP, it was radiolabeled with tritium. Furthermore, a sensitive, selective, and rapid liquid scintillation counter (LSC) method for quantifying 3H-SEP in biological matrix was validated. The lower quantification limit of the method was 4 Bq. The relative standard deviations (RSDs) of the intra- and inter-day precision were <3.0% and <3.9%, respectively. 3H-SEP was successfully applied to investigate the pharmacokinetics of SEP after intravenous administration of 20, 40, and 80 mg/kg (40 µCi/kg) in rats and 5, 10, and 20 mg/kg (6 µCi/kg) in beagles. The AUC(0-t) of SEP at three different doses was 487.81 ± 39.99 mg/L*h, 1,003.10 ± 95.94 mg/L*h, and 2,188.84 ± 137.73 mg/L*h in rats and 144.12 ± 3.78 mg/L*h, 322.62 ± 28.03 mg/L*h, and 754.17 ± 37.79 mg/L*h in beagles. The terminal elimination half-life (t1/2) of SEP was longer in beagles (204.29 ± 139.34 h) than in rats (35.48 ± 6.04 h). The concentration of SEP in plasma declined rapidly in both rats and beagles. All the study results provide detailed pharmacokinetic profiles of SEP in two kinds of animals, which will be helpful for further development.

Characterization and Antioxidant Evaluation of Four Kinds of Marine Oils in vitro.

The objective of this study was to characterize the lipid class and fatty acid composition of four kinds of marine oils including Phaeodactylum tricornutum oil (PO), Laminaria japonica oil (LO), krill oil (KO) and fish oil (FO), and evaluate their antioxidant capacities in vitro. The results indicated that compared to other three oils, PO showed the highest contents of total lipids and fucoxanthin (194.70 and 7.48 mg/g dry weight, respectively), the relatively higher content of long-chain polyunsaturated fatty acids including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (30.94 % in total fatty acids), and total phenolic content (675.88 mg gallic acid equivalent /100 g lipids), thereby contribute to great advantages in scavenging free radicals such as 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2-azino-bis (3-ethylbenzthiazoline)-6-sulfonic acid (ABTS), peroxyl radical, as well as reducing FRAP value. In conclusion, PO should be considered as a potential ingredient for dietary supplement with antioxidant capacity.

Characterization of volatile organic compounds with anti-atherosclerosis effects in Allium macrostemon Bge. and Allium chinense G. Don by head space solid phase microextraction coupled with gas chromatography tandem mass spectrometry.

Introduction: Allium macrostemon Bge. (AMB) and Allium chinense G. Don (ACGD) are both edible Allium vegetables and named officinal Xiebai (or Allii Macrostemonis Bulbus) in East Asia. Their medicinal qualities involve in lipid lowering and anti-atherosclerosis effects. And steroidal saponins, nitrogenous compounds and sulfur compounds are like the beneficial components responsible for medicinal functions. Sulfur compounds are the recognized main components both in the volatile oils of AMB and ACGD. Besides, few researches were reported about their holistic chemical profiles of volatile organic compounds (VOCs) and pharmacodynamic effects. Methods: In this study, we first investigated the lipid-lowering and anti-atherosclerotic effects of volatile oils derived from AMB and ACGD in ApoE -/- mice with high fat and high cholesterol diets. Results: The results showed the volatile oils of AMB and ACGD both could markedly reduce serum levels of TG, TC, and LDL-C (p < 0.05), and had no alterations of HDL-C, ALT, and AST levels (p > 0.05). Pathological results displayed they both could obviously improve the morphology of cardiomyocytes and the degree of myocardial fibrosis in model mice. Meanwhile, oil red O staining results also proved they could apparently decrease the lesion areas of plaques in the aortic intima (p < 0.05). Furthermore, head space solid phase microextraction coupled with gas chromatography tandem mass spectrometry combined with metabolomics analysis was performed to characterize the VOCs profiles of AMB and ACGD, and screen their differential VOCs. A total of 121 and 115 VOCs were identified or tentatively characterized in the volatile oils of AMB and ACGD, respectively. Relative-quantification results also confirmed sulfur compounds, aldehydes, and heterocyclic compounds accounted for about 85.6% in AMB bulbs, while approximately 86.6% in ACGD bulbs were attributed to sulfur compounds, ketones, and heterocyclic compounds. Multivariate statistical analysis showed 62 differentially expressed VOCs were observed between AMB and ACGD, of which 17 sulfur compounds were found to be closely associated with the garlic flavor and efficacy. Discussion: Taken together, this study was the first analysis of holistic chemical profiles and anti-atherosclerosis effects of AMB and ACGD volatile oils, and would benefit the understanding of effective components in AMB and ACGD.

A Fluorescent Probe Based on the Hydrazone Schiff Base for the Detection of Zn2+ and its Application on Test Strips.

A novel fluorescent probe SHK for Zn2+ detection was designed based on the hydrazone Schiff base, successfully synthesized by Suzuki coupling and condensation reactions. The probe SHK in DMSO/H2O showed extremely weak fluorescence. However, the solution exhibited an intensive yellow-green emission with the introduction of Zn2+. In contrast, negligible fluorescence change was observed when other metal ions were added, suggesting a high selectivity of SHK for Zn2+ detection. The Job's Plot analysis revealed that a 1:1 stoichiometric adduct SHK-Zn2+ formed during the Zn2+ sensing. The binding constant of the complex was determined to be 184 M- 1, and the detection limit for Zn2+ was calculated to be 112 µM. Moreover, the probe SHK achieved selective fluorescence sensing for Zn2+ on test strips, which guaranteed its practical application prospect.

Glutathione S-Transferases Mediate In Vitro and In Vivo Inactivation of Genipin: Implications for an Underlying Detoxification Mechanism.

Genipin (GP), the reactive metabolite of geniposide (GE), is responsible for GE-induced hepatotoxicity. As a potential detoxification pathway, the inactivation of GP by glutathione S-transferases (GSTs) has not yet been characterized. In this study, the thiol-GSH conjugates of GP, M532-1 and M532-2 were first identified and the catalytic activities of GSTs were investigated both in vitro and in vivo. GSTA1-1 and GSTA4-4 showed high activity in the formation of both thiol-GSH conjugates, whereas GSTA4-4 specifically catalyzed M532-2 formation in vitro. The active GST isoforms protect against alkylation of N-acetylcysteine (NAC), a classic model nucleophile. GST inhibition attenuated M532-1 formation in rat bile, confirming the in vivo catalytic role of GSTs. In conclusion, this study demonstrated the inactivation of GP by GSTs and implied that interindividual variability of GSTs may be a risk factor for susceptibility to GE-induced hepatotoxicity.