Americanin B inhibits pyroptosis in lipopolysaccharide-induced septic encephalopathy mice through targeting NLRP3 protein.

BACKGROUND: Sepsis is considered as a severe illness due to its high mortality. Sepsis can cause septic encephalopathy, thus leading to brain injury, behavioral and cognitive dysfunction. Pyroptosis is a type of regulated cell death (RCD) and takes a crucial part in occurrence and development of sepsis. Americanin B (AMEB) is a lignan compounds, which is extracted from Vernicia fordii. In our previous study, AMEB could inhibit microglial activation in inflammatory cell model. However, the function of AMEB in septic encephalopathy mice is uncertain. It would be worthwhile to ascertain the role and mechanism of AMEB in sepsis. PURPOSE: Current study designs to certify the relationship between pyroptosis and septic encephalopathy, and investigate whether AMEB can restrain NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome activation and restrict pyroptosis by targeting NLRP3 in septic mice model. STUDY DESIGN: C57BL/6 mice were utilized to perform sepsis model in vivo experiments. BV-2 cell lines were used for in vitro experiments. METHODS: In vivo sepsis model was established by lipopolysaccharide (LPS) intraperitoneal injection in male C57BL/6 J mice and in vitro model was exposed by LPS plus ATP in BV-2 cells. The survival rate was monitored on the corresponding days. NLRP3, apoptosis associated Speck-like protein (ASC), caspase-1, GasderminD (GSDMD), interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) level were detected by western blotting and immunofluorescence analysis. Molecular docking, cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS) experiments, RNAi transfection and quantitative real-time PCR were applied to confirm the potential target of AMEB. RESULTS: The results suggested that AMEB could rise survival percentage and lighten brain injury in LPS-induced sepsis mice. In addition, AMEB could inhibit pyroptosis and the activiation of NLRP3 inflammasome. The inhibiting function of AMEB on the activiation of NLRP3 inflammasome is weakened following si-NLRP3 transfection. Moreover, AMEB exerted anti-pyroptosis effect via targeting NLRP3 protein. CONCLUSIONS: Our findings first indicate NLRP3 is an effective druggable target for septic encephalopathy related brain injury, and also provide a candidate-AMEB for the treatment of septic encephalopathy. These emerging findings on AMEB in models of sepsis suggest an innovative approach that may be beneficial in the prevention of septic encephalopathy.

High SERS performance of functionalized carbon dots in the detection of dye contaminants.

INTRODUCTION: The long-term overuse of malachite green (MG) has potential carcinogenic, teratogenic, and mutagenic effects. The functional nanocomposite is novel and challenging to construct and implement through surface enhanced Raman scattering (SERS) strategy to reveal the contributions in application. OBJECTIVES: The novel Ag-CDs (carbon dots)-PBA (phenyl boric acid) nanocomposite was constructed by a facile route to detect toxic MG molecule with high SERS sensitivity and good uniformity. METHODS: The enhanced substrate used for the detection of MG has been successfully constructed using PBA modulated Ag-CDs on a structured surface with rich binding sites. RESULTS: The fabricated Ag-CDs-PBA substrate can be used to analyze various probe molecules exhibiting high sensitivity, good signal reproducibility, and excellent stability. The mechanism between components has been proved by calculations originating from the plasmonic Ag and active electronic transmission among the bridging CDs and PBA via the close spatial π-π effect. In addition, the accelerated separation of electron-hole pairs was triggered to further improve the SERS activity of the hybrid via a bidirectional charge transfer (CT) process. Significantly, the Ag-CDs-PBA system shows distinctive selectivity, in which PBA can hinder the interference of other species without specific hydroxyl groups. CONCLUSION: Based on this deeper insight on plasmon-mediated mechanism, the SERS substrate was successfully practiced for quantitative determination in real water and fish samples. The strategy developed promises to be a new sensor technology and has great potential for environmental and food safety applications.

p53-dependent HIF-1α /autophagy mediated glycolysis to support Cr(VI)-induced cell growth and cell migration.

Cr(VI) is known to be seriously toxic and carcinogenic. Hypoxia-inducible factor-1α (HIF-1α) is a crucial regulator to promote tumor development. In this study, we found that Cr(VI) significantly increased the expression of HIF-1α in A549 cells and in lung of BALB/c mice but not in HELF cells. Treatment with Lificiguat (YC-1), HIF-1α inhibitor, or CoCl2, HIF-1α inducer, could alter Cr(VI)-induced autophagy, glycolysis, and cell growth in A549 cells but not in HELF cells, validating the involvement of HIF-1α in these effects of Cr(VI) in A549 cells. Co-treatments of pcATG4B with YC-1, or siATG4B with CoCl2 demonstrated the role of HIF-1α / autophagy axis in inducing glycolysis and cell growth in A549 cells. In HELF cells, however, only autophagy but not HIF-1α played a role in inducing glycolysis. The protein level of p53 was significantly lower in A549 cells than in HELF cells. RITA, a p53 inducer, attenuated Cr(VI)-induced HIF-1α and LC3-II in A549 cells, suggesting that p53 might be the mechanism underlying the different effects of Cr(VI) on HIF-1α in A549 and HELF cells. Thus, p53-dependent HIF-1α / autophagy-mediated glycolysis plays a role in facilitating Cr(VI)-induced carcinogenesis.

De Novo Generation and Identification of Novel Compounds with Drug Efficacy Based on Machine Learning.

One of the main challenges in small molecule drug discovery is finding novel chemical compounds with desirable activity. Traditional drug development typically begins with target selection, but the correlation between targets and disease remains to be further investigated, and drugs designed based on targets may not always have the desired drug efficacy. The emergence of machine learning provides a powerful tool to overcome the challenge. Herein, a machine learning-based strategy is developed for de novo generation of novel compounds with drug efficacy termed DTLS (Deep Transfer Learning-based Strategy) by using dataset of disease-direct-related activity as input. DTLS is applied in two kinds of disease: colorectal cancer (CRC) and Alzheimer's disease (AD). In each case, novel compound is discovered and identified in in vitro and in vivo disease models. Their mechanism of actionis further explored. The experimental results reveal that DTLS can not only realize the generation and identification of novel compounds with drug efficacy but also has the advantage of identifying compounds by focusing on protein targets to facilitate the mechanism study. This work highlights the significant impact of machine learning on the design of novel compounds with drug efficacy, which provides a powerful new approach to drug discovery.

Effect of hot electron induced charge transfer generated by surface plasmon resonance on Ag@Au/ITO/PNTP systems.

The present study discusses the fabrication of a bimetallic material consisting of silver nanorods and gold nanospheres (designated Ag@Au), and its surface modification with 4-nitrothiophenol (PNTP) after deposition on an indium tin oxide (ITO) glass sheet, followed by laser irradiation at various wavelengths. The results indicate that the reduction of PNTP is more complete under irradiation at 532 nm due to the surface plasmon resonance (SPR) effects of the gold and silver nanomaterials. Moreover, the surface enhanced Raman scattering (SERS) of the PNTP adsorbed on the Ag@Au/ITO is found to be significantly stronger than that of PNTP adsorbed on Ag@Au alone, due to charge transfer (CT) at the interface. In addition, the SERS enhancement effect of the PNTP molecules on the Ag@Au/ITO substrate is optimal under 532 nm laser irradiation due to the hot electron-induced CT generated by the SPR effect. Thus, the system constructed herein combines the effects of SPR and CT, thereby assisting in a further understanding of the enhancement mechanism of SERS and, hence, the further development SERS research in metal-semiconductor-molecular systems.

Melatonin Protects Injured Spinal Cord Neurons From Apoptosis by Inhibiting Mitochondrial Damage via the SIRT1/Drp1 Signaling Pathway.

Spinal cord injuries (SCIs) often result in limited prospects for recovery and a high incidence of disability. Melatonin (Mel), a hormone, is acknowledged for its neuroprotective attributes. Mel was examined in this study to discover if it alleviates SCIs via the sirtuin1/dynamin-related protein1 (SIRT1/Drp1) signaling pathway. SCIs were simulated in mice by inducing cord contusion at the T9-T10 vertebrae and causing inflammation in primary spinal neurons using lipopolysaccharide (LPS). The findings of our study demonstrated that Mel treatment effectively promoted neuromotor recovery through multiple mechanisms, including the reduction of neuronal death, suppression of astrocyte and microglia activation, and attenuation of neuroinflammation. Moreover, Mel therapy significantly upregulated the expression of SIRT1 in both spinal cord tissues and spinal neurons of mice. Additionally, Mel exhibited the potential to mitigate neuronal mitochondrial dysfunction by modulating the levels of Drp1 and TOMM20, thereby addressing the underlying factors contributing to this dysfunction. Furthermore, when SIRT1 was downregulated, it reversed the positive effects of Mel. Overall, our present study suggests that Mel has the capacity to modulate the SIRT1/Drp1 pathway, thereby ameliorating mitochondrial dysfunction, attenuating inflammation and apoptosis, and enhancing neural function subsequent to SCIs.

Crebanine ameliorates ischemia-reperfusion brain damage by inhibiting oxidative stress and neuroinflammation mediated by NADPH oxidase 2 in microglia.

BACKGROUND: The urgent challenge for ischemic stroke treatment is the lack of effective neuroprotectants that target multiple pathological processes. Crebanine, an isoquinoline-like alkaloid with superior pharmacological activities, presents itself as a promising candidate for neuroprotection. However, its effects and mechanisms on ischemic stroke remain unknown. METHODS: The effects of crebanine on brain damage following ischemic stroke were evaluated using the middle cerebral artery occlusion and reperfusion (MCAO/R) model. Mechanism of action was investigated using both MCAO/R rats and lipopolysaccharide (LPS)-activated BV-2 cells. RESULTS: We initially demonstrated that crebanine effectively ameliorated the neurological deficits in MCAO/R rats, while also reducing brain edema and infarction. Treatment with crebanine resulted in the up-regulation of NeuN+ fluorescence density and down-regulation of FJB+ cell count, and mitigated synaptic damage. Crebanine attenuated the hyperactivation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) by downregulating NADP+ and NADPH levels, suppressing gp91phox and p47phox expressions, and reducing p47phox membrane translocation in Iba-1+ cells. Additionally, crebanine reduced the quantity of Iba-1+ cells and protein expression. Correlation analysis has demonstrated that the inhibition of NOX2 activation in microglia is beneficial for mitigating I/R brain injuries. Moreover, crebanine exhibited significant antioxidant properties by down-regulating the expression of superoxide anion and intracellular reactive oxygen species in vivo and in vitro, and reducing lipid and DNA peroxidation. Crebanine exerted anti-inflammatory effect, as evidenced by the reduction in the expressions of nitric oxide, interleukin 1ß, tumor necrosis factor α, interleukin 6, and inducible nitric oxide synthase. The effect of crebanine was achieved through the suppression of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPK) signaling pathway. This is supported by evidence showing reduced NF-κB p65 promoter activity and nucleus translocation, as well as suppressed IκBα phosphorylation and degradation. Additionally, it inhibited the phosphorylation of ERK, JNK, and p38 MAPKs. Importantly, the anti-oxidative stress and neuroinflammation effects of crebanine were further enhanced after silencing gp91phox and p47phox. CONCLUSION: Crebanine alleviated the brain damages of MCAO/R rats by inhibiting oxidative stress and neuroinflammation mediated by NOX2 in microglia, implying crebanine might be a potential natural drug for the treatment of cerebral ischemia.

Data-Knowledge-Driven Modeling and Operational Adjustment for the Pharmaceutical Tablet Manufacturing Process via Wet Granulation.

In the context of Pharma 4.0, pharmaceutical quality control (PQC) is beset by issues such as uncertainties from ever-changing critical material attributes and strong coupling between variables in the multi-unit pharmaceutical tablet manufacturing process (PTMP), and how to timely adjust the operational variables to deal with such challenges has become a key problem in PQC. In this study, we propose a novel data-knowledge-driven modeling and operational adjustment framework for PTMP by integrating Bayesian network (BN) and case-based reasoning (CBR). At the modeling level, first, a distributed concept is introduced, i.e., the BN model for each subunit of PTMP is established in accordance with the operation process sequence, and the transition variables are given by the BN model established first and retrieved as the new query for the next unit. Once the BN models of all subunits are built, they are integrated into a global BN model. At the operational adjustment level, by taking the expected critical quality attributes (CQAs) and related prior information as evidence, the operational adjustment is achieved through global BN reasoning. Finally, the case study in a sprayed fluidized-bed granulation-based PTMP demonstrates the feasibility and effectiveness in improving the terminal CQAs of the proposed method, which is also compared with other methods to showcase its efficacy and merits.

1H NMR-guided isolation of hasubanan alkaloids from the alkaloidal extract of Stephania longa.

1H NMR-guided fractionation led to the isolation of 16 alkaloids from the alkaloidal extract of Stephania longa, including 11 new hasubanan alkaloids (1-11) and five known alkaloids (12-16). Interestingly, compounds 2 and 11 are typically considered protonated tertiary amine compounds, whereas compounds 1 and 10 are regarded as oxidized versions of the corresponding compounds. Their gross structures were determined through an extensive analysis of spectroscopic data (NMR (nuclear magnetic resonance) and HRESIMS (high resolution electrospray ionization mass spectroscopy)), and their absolute configurations were established by comparing their experimental and calculated electronic circular dichroism (ECD) spectra. The new (3) and a known (12) compounds in all isolates displayed stronger antineuroinflammatory effects (IC50 values of 1.8 and 11.1 µM, respectively) than minocycline (IC50 value of 15.5 µM) against NO production on LPS-activated BV2 cells.

Cbl induced ubiquitination of HER2 mediate immune escape from HER2-targeted CAR-T.

Breast cancer (BC) with high HER2 expression has higher recurrence rate and worse prognosis, and its immunotherapy is promising. Based on the high expression of HER2, develop Chimeric Antigen Receptor T-cell (CAR-T) and PDL-1 immunotherapy, and study the molecular pathways of related immune cells and recurrence. HER2-CAR-T cells were constructed using retroviruses, and their specific recognition and immune effects on HER2+ BC cells were verified by in vivo and in vitro experiments. PDL-1 was used as adjuvant immunotherapy, knocking down PDL-1 in tumor cells or dendritic cells, or depleted macrophages to study immune pathways. The negative regulation of HER2 by cbl was determined by IP, ubiquitination experiments, and segmented plasmids, elucidating the molecular mechanism of HER2+ BC recurrence after immunotherapy. HER2-CAR-T specifically recognizes HER2-positive tumor cells and inhibits tumor growth in vivo and in vitro, and anti-PDL1 treatment enhances the therapeutic effect of HER2-CAR-T on tumors. HER2-CART therapy eradicated solid tumors after PDL1 knockdown in dendritic cells. Immunotherapy of relapsed tumors lost HER2 expression by upregulating cbl. HER2-CAR-T shows specific recognition of HER2+ cells and can mediate immune response therapy with the cooperation of PDL-1.

Isoamericanin A improves lipopolysaccharide-induced memory impairment in mice through suppression of the nicotinamide adenine dinucleotide phosphateoxidase-dependent nuclear factor kappa B signaling pathway.

Alzheimer's disease (AD) is the most frequent cause of dementia in the elderly. Isoamericanin A (ISOA) is a natural lignan possessing great potential for AD treatment. This study investigated the efficacy of ISOA on memory impairments in the mice intrahippocampal injected with lipopolysaccharide (LPS) and the underlying mechanism. Y-maze and Morris Water Maze data suggested that ISOA (5 and 10 mg/kg) ameliorated short- and long-term memory impairments, and attenuated neuronal loss and lactate dehydrogenase activity. ISOA exerted anti-inflammatory effect demonstrating by the reduction of ionized calcium-binding adapter molecule 1 positive cells and suppression of marker protein and pro-inflammation cytokines expressions induced by LPS. ISOA suppressed the nuclear factor kappa B (NF-κB) signaling pathway by inhibiting IκBα phosphorylation and NF-κB p65 phosphorylation and nuclear translocation. ISOA inhibited superoxide and intracellular reactive oxygen species accumulation by reducing nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation, demonstrating by suppressing NADP+ and NADPH contents, gp91phox expression, and p47phox expression and membrane translocation. These effects were enhanced in combination with NADPH oxidase inhibitor apocynin. The neuroprotective effect of ISOA was further proved in the in vitro models. Overall, our data revealed a novel pharmacological activity of ISOA: ameliorating memory impairment in AD via inhibiting neuroinflammation.

Complexation of a Nitrilotriacetate-Derived Triamide Ligand with Trivalent Lanthanides: A Thermodynamic and Crystallographic Study.

Non-heterocyclic N-donor nitrilotriacetate-derived triamide ligands are one of the most promising extractants for the selective extraction separation of trivalent actinides over lanthanides, but the thermodynamics and mechanism of the complexation of this kind of ligand with actinides and lanthanides are still not clear. In this work, the complexation behaviors of N,N,N',N',N″,N″-hexaethylnitrilotriacetamide (NTAamide(Et)) with four representative trivalent lanthanides (La3+, Nd3+, Eu3+, and Lu3+) were systematically investigated by using 1H nuclear magnetic resonance (1H NMR), ultraviolet-visible (UV-vis) and fluorescence spectrophotometry, microcalorimetry, and single-crystal X-ray diffractometry. 1H NMR spectroscopic titration of La3+ and Lu3+ indicates that two species of 1:2 and 1:1 metal-ligand complexes were formed in NO3- and ClO4- media. The stability constants of NTAamide(Et) with Nd3+ and Eu3+ obtained by UV-vis and fluorescence titration show that the complexing strength of NTAamide(Et) with Nd3+ is lower than that with Eu3+ in the same anionic medium, while that of the same lanthanide complex is higher in ClO4- medium than in NO3- medium. Meanwhile, the formation reactions for all metal-ligand complexes are driven by both enthalpy and entropy. The structures of lanthanide complexes in the single ClO4- and NO3- medium and the mixed one were determined to be [LnL2(MeOH)](ClO4)3 (Ln = La, Nd, Eu, and Lu), [LaL2(EtOH)2][La(NO3)6], and [LaL2(NO3)](ClO4)2, separately. The average bond lengths of lanthanide complexes decrease gradually with the decrease in ionic radii of Ln3+, indicating that heavier lanthanides form stronger complexes due to the lanthanide contraction effect, which coincides with the trend of the complexing strength obtained by spectroscopic titration. This work not only reveals the thermodynamics and mechanism of the complexation between NTAamide ligands and lanthanides but also obtains the periodic tendency of complexation between them, which may facilitate the separation of trivalent lanthanides from actinides.

Efficacy and safety of novel carbapenem-ß-lactamase inhibitor combinations: imipenem-cilastatin/relebactam results from randomized controlled trials.

Background: Gram-negative bacteria is a global public health problem. Treatment options include novel beta-lactamase inhibitors. Objectives: The objective of this study was to collect information on the efficacy and safety of novel ß-lactamase inhibitor combinations such as imipenem-cilastatin/relebactam (IMI/REL). Methods: In order to comprehensively evaluate the clinical, microbiological, and adverse events outcomes, a meta-analysis was conducted on clinical trials comparing novel ß-lactamase inhibitor combinations with existing comparator therapies. Results: Four studies comprising 948 patients were included in the analysis. IMI/REL therapy demonstrated similar clinical responses to comparators across various treatment visits, including discontinuation of intravenously administered therapy visits [DCIV, RR = 1.00 (0.88, 1.12)], early follow-up visits [EFU, RR = 1.00 (0.89, 1.14)], late follow-up visits [LFU, RR = 1.00 (0.88, 1.13)]. Moreover, no significant difference in the microbiologic response of MITT patients was observed between IMI/REL and comparators across DCIV [RR = 0.99 (0.89, 1.11)], EFU [RR = 1.01 (0.95, 1.07)], and LFU visits [RR = 1.00 (90.94, 1.07)]. In terms of safety, therapy with IMI/REL and comparators exhibited similar risks of at least one adverse event (AE), drug-related AEs, and discontinuation due to AEs. The incidence of serious AEs (SAEs) was significantly lower in the IMI/REL group compared to the comparison groups. The predominant AEs were gastrointestinal disorders, with no significant difference observed between the IMI/REL group and comparators. Conclusion: The clinical and microbiologic response to IMI/REL in the treatment of bacterial infection was comparable to that of the comparator. Furthermore, the incidence of AEs and the tolerability of IMI/REL were similar among the comparators. Based on these findings, IMI/REL can be considered as a viable alternative treatment option.

Insights into the spontaneous multi-scale supramolecular assembly in an ionic liquid-based extraction system.

Herein, we report a four-step mechanism for the spontaneous multi-scale supramolecular assembly (MSSA) process in a two-phase system concerning an ionic liquid (IL). The complex ions, elementary building blocks (EBBs), [EBB]n clusters and macroscopic assembly (MA) sphere are formed step by step. The porous large-sized [EBB]n clusters in the glassy state can hardly stay in the IL phase and they transfer to the IL-water interface due to both electroneutrality and amphiphilicity. Then, the clusters undergo random collision in the interface driven by the Marangoni effect and capillary force thereafter. Finally, a single MA sphere can be formed owing to supramolecular interactions. To our knowledge, this is the first example realizing spontaneous whole-process supramolecular assembly covering microscopic, mesoscopic and macroscopic scales in extraction systems. The concept of multi-scale selectivity (MSS) is therefore suggested and its mechanism is revealed. The selective separation and solidification of metal ions can be realized in a MSSA-based extraction system depending on MSS. In addition, insights into the physicochemical characteristics of ILs from microscopic, mesoscopic to macroscopic scales are provided, and especially, the solvation effect of ILs on the large-sized clusters leading to the phase-splitting is examined. It is quite important that the polarization of uranyl in its complex, the growing of uranyl clusters in an IL as well as the glassy material of uranyl are investigated systematically on the basis of both experiment and theoretical calculations in this work.

Comparative analysis of the endophytic bacteria inhabiting the phyllosphere of aquatic fern Azolla species by high-throughput sequencing.

BACKGROUND: Azolla is a small floating fern living in symbiosis with nitrogen-fixing cyanobacteria and provides a variety of important ecosystem benefits. Previous studies have presented that Azolla harbors diverse bacteria that may play a key role in host fitness and productivity. However, the characteristics of endophytic bacteria inhabiting the phyllosphere of different species of Azolla have not yet been fully understood. RESULTS: In this study, the 16S ribosomal DNA (rDNA) V5-V7 region of bacteria was determined by Illumina high-throughput sequencing platform to study the diversity and richness of endophytic bacterial communities in the phyllosphere of five Azolla species collected from different countries. A total of 1150 operational taxonomic units (OTUs) were detected for the endophytic bacteria community. According to the α diversity indices, the diversity of bacteria was ordered as Azolla imbricata > A. pinnata > A. filiculoides > A. mexicana > A. caroliniana. The PCoA results displayed that the bacterial communities of A. mexicana and A. caroliniana shared the highest similarity, followed by the similarity between A. pinnata and A. imbricata, and they were significantly distinct from the community of A. filiculoides. The dominant bacteria of Azolla mainly belonged to the phylum of Proteobacteria, followed by Actinobacteria, Chlorobillobacteria, and Firmicutes. In detail, the relative abundance of Proteobacteria in A. imbricata was 52.23%, whereas it was more than 80.00% in the other four species of Azolla. Notably, Herbaspirillum (45.91%, 44.08%) and Methylophilus (29.97%, 37.96%) were the main genera inhabiting A. mexicana and A. caroliniana respectively. Ferrovibrio (18.54%) and Rhizobium (16.68%) were the dominant genera inhabiting A. filiculoides. The group of unidentified genera (41.63%, 44.92%) consisted most of the bacteria in A. imbricata and A. pinnata respectively. Further analysis suggested that the significant different bacteria identified in LDA Effect Size analysis existed Azolla species-specific patterns. CONCLUSIONS: In summary, all results suggested that the diversity and composition of the endophytic bacterial communities were different in Azolla species.

The IPGA1-ANGUSTIFOLIA module regulates microtubule organisation and pavement cell shape in Arabidopsis.

Plant cells continuously experience mechanical stress resulting from the cell wall that bears internal turgor pressure. Cortical microtubules align with the predicted maximal tensile stress direction to guide cellulose biosynthesis and therefore results in cell wall reinforcement. We have previously identified Increased Petal Growth Anisotropy (IPGA1) as a putative microtubule-associated protein in Arabidopsis, but the function of IPGA1 remains unclear. Here, using the Arabidopsis cotyledon pavement cell as a model, we demonstrated that IPGA1 forms protein granules and interacts with ANGUSTIFOLIA (AN) to cooperatively regulate microtubule organisation in response to stress. Application of mechanical perturbations, such as cell ablation, led to microtubule reorganisation into aligned arrays in wild-type cells. This microtubule response to stress was enhanced in the IPGA1 loss-of-function mutant. Mechanical perturbations promoted the formation of IPGA1 granules on microtubules. We further showed that IPGA1 physically interacted with AN both in vitro and on microtubules. The ipga1 mutant alleles exhibited reduced interdigitated growth of pavement cells, with smooth shape. IPGA1 and AN had a genetic interaction in regulating pavement cell shape. Furthermore, IPGA1 genetically and physically interacted with the microtubule-severing enzyme KATANIN. We propose that the IPGA1-AN module regulates microtubule organisation and pavement cell shape.

Factors associated with psychological resilience in patients with chronic heart failure and efficacy of psycho-cardiology intervention.

OBJECTIVE: To explore the value of psycho-cardiology intervention on psychological resilience in patients with chronic heart failure (CHF) and investigate the associated factors. METHODS: A retrospective study of 142 patients with CHF was carried out. These patients were admitted to the Department of Cardiology, Provincial Clinical Medical College of Fujian Medical University from January 2017 to January 2021. They were grouped according to intervention method, including 74 patients with psycho-cardiology intervention and 68 with conventional intervention. The psychological resilience and the levels of anxiety and depression before and after intervention were assessed with the Connor-Davidson resilience scale (CD-RISC), self-rating anxiety scale (SAS), and self-rating depression scale (SDS), respectively. The factors associated with psychological resilience in patients with CHF were observed. The relationship between psychological resilience and SAS scores before intervention was studied. RESULTS: Using multivariate logistic regression analysis, we found that age (OR (95% CI): 3.452 (0.862-4.872), P=0.015), gender (OR, (95% CI): 3.389 (0.872-5.023), P=0.035), SAS score (OR (95% CI) 5.433 (1.543-14.333), P=0.027) and SDS score (OR (95% CI): 5.654 (1.572-15.823), P=0.021) were factors associated with psychological resilience in patients with CHF (all P<0.05). The average CD-RISC scores were 56.55±8.89 points in patients with CHF. The psychological resilience was inversely correlated with SAS score (r=-0.450, P<0.001) and SDS scores (r=-0.401, P<0.001). The CD-RISC scores of the observation group after intervention were higher than before intervention and higher than the control group, while SAS and SDS scores were decreased (all P<0.05). CONCLUSION: Age, gender, SAS, and SDS scores are factors associated with psychological resilience in patients with CHF. Psychological resilience was inversely associated with both anxiety and depression. Psycho-cardiology intervention can improve patients' psychological resilience, and reduce their anxiety and depression.

Plasmonic Ag decorated AlOOH for highly sensitive SERS detection of affinity OH groups molecules enriched in hotspots.

Significant breakthroughs have been made in the development of surface-enhanced Raman scattering (SERS) substrates constructed by depositing plasmonic Ag onto nanostructured platforms. AlOOH is widely fabricated using hydrothermal, microwave, and microemulsion methods. Among these, the high catalytic activity of AlOOH prepared by the microemulsion method is derived from its high specific surface area, more active surface OH groups, and multi-active adsorption sites. And nanomaterials with such excellent properties have not yet been fabricated on a SERS-based platform to improve the Raman-enhanced properties of Ag achieving high-sensitivity detection of probe molecules especially with affinity for OH groups. The precious metal Ag has long been known to serve as traps to capture electrons and holes generated by plasmon resonance, reducing electron-hole recombination and exhibiting high activity in photocatalytic processes. In this work, to demonstrate the SERS substrate activity of the AlOOH@Ag complex, it has been successfully applied to identify congo red (CR) molecules with high sensitivity, methyl blue (MB) and methyl orange (MO), enabling trace-level detection with enhanced performance much stronger than Ag substrate.

Lignanamides from the stems of Piper hancei maxim. and their anti-inflammatory and cytotoxic activities.

Four new lignanamides, hancamides A - D (1-4), together with four known analogs (5-8), were isolated from the stems of Piper hancei Maxim. Their structures were determined based on 1D and 2D NMR, IR, UV, and HR-ESIMS spectroscopic analysis as well as by comparison with the reported data. All the isolates exhibited potential inhibitory effects on NO production in LPS-induced BV-2 microglial cells, with IC50 values of 4.26-40.68 µM. Moreover, compounds 2 and 8 displayed moderate cytotoxic activities against MGC-803, HepG2, SKOV-3, T24, and HeLa cells, with IC50 values ranging from 13.57 to 34.20 µM, respectively.

Probing the Difference in the Complexation of Trivalent Actinides and Lanthanides with a Tridentate N,O-Hybrid Ligand: Spectroscopy, Thermodynamics, and Coordination Modes.

Comparatively revealing the complexation behavior of trivalent actinides and lanthanides with functional ligands in aqueous solution is of great importance to enrich our knowledge on the fundamental coordination chemistry of trivalent f-block elements and to control the fate of minor actinides in nuclear fuel cycles. In this work, the complexation of Am(III) and Nd(III), representatives for trivalent actinides and lanthanides, respectively, with a N,O-hybrid ligand 6-(dimethylcarbamoyl)picolinic acid (DMAPA, denoted as HL) was investigated by absorption spectroscopy, calorimetry, X-ray crystallography, and density functional theory (DFT) calculations. Successive formation of 1:1, 1:2, and 1:3 (metal/ligand) complexes of Am(III) and Nd(III) with DMAPA was identified, and the corresponding thermodynamic parameters were determined. The binding strength of Am(III) with DMAPA is slightly stronger than that of Nd(III), and the complexation of Nd(III) with DMAPA is mainly entropy-driven. The crystal structure of the 1:2 Nd(III)/DMAPA complex and the DFT calculation shed additional light on the coordination and structural characteristics of the complexes. In contrast to the Nd-N bond in the Nd(III)/DMAPA complex, the Am-N bond in the Am(III)/DMAPA complex exhibits more covalency, which contributes to the slightly stronger complexation of Am(III) with DMAPA.