Self-Stigma and Mental Health in Divorced Single-Parent Women: Mediating Effect of Self-Esteem.

Numerous studies have addressed the issue of "self-stigma" among divorced single-parent women. However, there is a scarcity of quantitative data available on this subject. Moreover, while self-esteem is a crucial factor throughout life, it has been extensively studied in the context of "children" from single-parent families, but not from the perspective of parents themselves. To address this gap, the present study aimed to explore the relationship between self-stigma, self-esteem, and mental health in 347 divorced, single-parent women. The online survey recruited participants randomly, with a specific focus on single mothers who were divorced and had more than one child under the age of 18. The analysis involved utilizing SPSS 25.0 (IBM Co., Armonk, NY, USA) and PROCESS Macro Version 4.1 (Model 4) to conduct descriptive statistics, frequency analysis, reliability assessment, correlation analysis, and mediating analysis. The findings revealed that self-esteem played a partial mediating role in the relationship between self-stigma and mental health. In other words, higher levels of self-stigma among divorced, single-parent women were associated with poorer mental health outcomes. Additionally, the study discovered that engaging in more self-stigma was linked to lower self-esteem and increased mental health distress. These results underscore the significance of internal factors, such as self-stigma and self-esteem, and highlight their relevance in formulating policies aimed at supporting divorced single-parent women. Policymakers should take these factors into account to develop effective strategies to aid this specific group.

ITC-6102RO, a novel B7-H3 antibody-drug conjugate, exhibits potent therapeutic effects against B7-H3 expressing solid tumors.

BACKGROUND: The B7-H3 protein, encoded by the CD276 gene, is a member of the B7 family of proteins and a transmembrane glycoprotein. It is highly expressed in various solid tumors, such as lung and breast cancer, and has been associated with limited expression in normal tissues and poor clinical outcomes across different malignancies. Additionally, B7-H3 plays a crucial role in anticancer immune responses. Antibody-drug conjugates (ADCs) are a promising therapeutic modality, utilizing antibodies targeting tumor antigens to selectively and effectively deliver potent cytotoxic agents to tumors. METHODS: In this study, we demonstrate the potential of a novel B7-H3-targeting ADC, ITC-6102RO, for B7-H3-targeted therapy. ITC-6102RO was developed and conjugated with dHBD, a soluble derivative of pyrrolobenzodiazepine (PBD), using Ortho Hydroxy-Protected Aryl Sulfate (OHPAS) linkers with high biostability. We assessed the cytotoxicity and internalization of ITC-6102RO in B7-H3 overexpressing cell lines in vitro and evaluated its anticancer efficacy and mode of action in B7-H3 overexpressing cell-derived and patient-derived xenograft models in vivo. RESULTS: ITC-6102RO inhibited cell viability in B7-H3-positive lung and breast cancer cell lines, inducing cell cycle arrest in the S phase, DNA damage, and apoptosis in vitro. The binding activity and selectivity of ITC-6102RO with B7-H3 were comparable to those of the unconjugated anti-B7-H3 antibody. Furthermore, ITC-6102RO proved effective in B7-H3-positive JIMT-1 subcutaneously xenografted mice and exhibited a potent antitumor effect on B7-H3-positive lung cancer patient-derived xenograft (PDX) models. The mode of action, including S phase arrest and DNA damage induced by dHBD, was confirmed in JIMT-1 tumor tissues. CONCLUSIONS: Our preclinical data indicate that ITC-6102RO is a promising therapeutic agent for B7-H3-targeted therapy. Moreover, we anticipate that OHPAS linkers will serve as a valuable platform for developing novel ADCs targeting a wide range of targets.

Effect of a ZrO2 Seed Layer on an Hf0.5Zr0.5O2 Ferroelectric Device Fabricated via Plasma Enhanced Atomic Layer Deposition.

In this study, a ferroelectric layer was formed on a ferroelectric device via plasma enhanced atomic layer deposition. The device used 50 nm thick TiN as upper and lower electrodes, and an Hf0.5Zr0.5O2 (HZO) ferroelectric material was applied to fabricate a metal-ferroelectric-metal-type capacitor. HZO ferroelectric devices were fabricated in accordance with three principles to improve their ferroelectric properties. First, the HZO nanolaminate thickness of the ferroelectric layers was varied. Second, heat treatment was performed at 450, 550, and 650 °C to investigate the changes in the ferroelectric characteristics as a function of the heat-treatment temperature. Finally, ferroelectric thin films were formed with or without seed layers. Electrical characteristics such as the I-E characteristics, P-E hysteresis, and fatigue endurance were analyzed using a semiconductor parameter analyzer. The crystallinity, component ratio, and thickness of the nanolaminates of the ferroelectric thin film were analyzed via X-ray diffraction, X-ray photoelectron spectroscopy, and transmission electron microscopy. The residual polarization of the (20,20)*3 device heat treated at 550 °C was 23.94 µC/cm2, whereas that of the D(20,20)*3 device was 28.18 µC/cm2, which improved the characteristics. In addition, in the fatigue endurance test, the wake-up effect was observed in specimens with bottom and dual seed layers, which exhibited excellent durability after 108 cycles.

Polymer-flooding produced water treatment using an electro-hybrid ozonation-coagulation system with novel cathode membranes targeting alternating filtration and in situ self-cleaning.

Polymer-flooding produced water is more difficult to treat for reinjection compared with normal produced water because of the presence of residual hydrolyzed polyacrylamide (HPAM). A novel cathode membrane integrated electro-hybrid ozonation-coagulation (CM-E-HOC) process was proposed for the treatment of polymer-flooding produced water. This process achieved in situ self-cleaning by generated microbubbles in the cathode membrane. The CM-E-HOC process achieved a higher suspended solid (SS), turbidity and PAM removal efficiency than the CM-EC process. The SS in the CM-E-HOC effluent was ≤ 20 mg/L SS, which met the reinjection requirements of Longdong, Changqing Oilfield, China (Q/SYCQ 08,011-2019) at different current densities (3, 5 and 10 mA/cm2). The CM-E-HOC process greatly mitigated both reversible and irreversible membrane fouling. Therefore, excellent flux recovery was obtained at different in situ self-cleaning intervals during the CM-E-HOC process. Furthermore, alternating filtration achieved continuous water production during the CM-E-HOC process. On one hand, the effective removal of aromatic protein-like substances and an increase in oxygen-containing functional groups were achieved due to the enhanced oxidation ability of the CM-E-HOC process, which decreased membrane fouling. On the other hand, the CM-E-HOC process showed improved coagulation performance because of the increased oxygen-containing functional groups and polymeric Fe species. Therefore, larger flocs with higher fractal dimensions were generated, and a looser and more porous cake layer was formed on the membrane surface during the CM-E-HOC process. Consequently, the CM-E-HOC process exhibited better in situ self-cleaning performance and lower filtration resistance than the CM-EC process.

Removal effect of trihalomethanes (THMs) and halogenated acetic acids (HAAs) precursors in reclaimed water by polyaluminum chloride (PACl) coagulation.

This study analyzed the removal effect of various doses of polyaluminum chloride (PACI) on wastewater treatment plants at pH 7. The sewage plant's secondary effluent organic matter (EfOM) separates into four components: hydrophobic base (HOB), hydrophilic (HI), hydrophobic acid (HOA), and hydrophobic neutral (HON). The removal effect for various forms of organic waste is optimum at 16 mg/L and that halogenated acetic acids (HAAs) and trihalomethanes (THMs) are formed simultaneously. After PACI treatment, hydrophobic organic compounds were converted to humic acid (HA), fulvic acid (FA), soluble microbial products (SMPs), and other HI organic compounds, increasing the amount of HAAs produced by HI fractions. Removal rate of hydrophobic organic compounds, particularly HON, is 92.8% when using PAC. Moreover, after EfOM coagulation, most HAAs are trichloroacetic acid (TCAA), followed by bromochloroacetic acid (BCAA) and bromodichloroacetic acid (BDCAA). Only HOB can produce monochloroacetic acid (MCAA), whereas HA and SMPs with HOA are primary components of dichloroacetic acid (DCAA). The toughest removable byproduct of THMs is CHBr3, and after condensation of each THM component, only HOA and HON produce CHBr3, while HI produces only a minimal quantity of CHBrCl2 and CHCl3.This finding is critical for understanding how disinfection byproducts are produced after chlorinating EfOM.

Unraveling the over-oxidation inhibition mechanism during the hybrid ozonation-coagulation process: Immediate entrapment and complexation between intermediate organic matter and coagulants.

Pre-ozonation coagulation process had a very low and narrow range of ozone dosages for enhancing the dissolved organic matter (DOC) removal efficiency, in which over-oxidation may occur if the ozone dosage was not strictly controlled. In contrast, the proposed hybrid ozonation-coagulation (HOC) process with higher oxidation ability notably inhibited over-oxidation in this study, and exhibited improved DOC removal efficiency compared with coagulation at a much wider range of ozone dosages at different initial pH for the treatment of WWTP effluent. The HOC process also had a higher DOC removal efficiency than pre-ozonation coagulation. According to zeta potential analysis, a rising trend indicated that complexation between organic matter and metal coagulants persisted throughout the HOC process. However, the zeta potential remained almost unchanged during subsequent coagulation after pre-ozonation at high ozone dosages. Synchronous fluorescence spectroscopy analysis revealed that immediate entrapment and complexation between hydrolysed coagulants and oxidized intermediate organic matter occurred in the HOC process. Furthermore, FT-IR analysis showed that more oxygen-containing functional groups were generated, which were effectively trapped by metal coagulants and readily flocculated. To further prove the immediate entrapment and complexation during the HOC process, UPLC-Q-TOF-MS was applied to analyze the intermediate organic matter in the supernatant and flocs. The results implied that C21- organic matter was oxidized and decomposed into C11-C20, and C11-C20 intermediate organic matter was trapped and complexed by metal coagulants once formed, which led to the increase of C11-C20 in the flocs. Nevertheless, the catalytic ozonation process (γ-Al2O3/O3) with the same oxidation ability as the HOC process decomposed the organic matter into C1-C10. XPS analysis further confirmed the immediate entrapment and removal of aliphatic/aromatic carbon and oxygen-containing functional groups during the HOC process. Therefore, over-oxidation can be effectively inhibited, and wide range of ozone dosages was obtained during the HOC process, which facilitate the application of the HOC process.

Changes in the structural characteristics of EfOM during coagulation by aluminum chloride and the effect on the formation of disinfection byproducts.

The effects of coagulation on the removal efficiency of different fractions of effluent organic matter (EfOM) from wastewater treatment plants were investigated to identify changes in their structural characteristics and the influences on trihalomethane formation potential (THMFP) and haloacetic acid formation potential (HAAFP). The results indicated that coagulation performed better for the removal of hydrophobic base (HOB) and hydrophobic neutral (HON) fractions than hydrophilic (HI) and hydrophobic acid (HOA) fractions. The removal efficiency was higher under neutral than under acidic conditions for all fractions. As a result, lower levels of THMFP and HAAFP were detected at pH7. The excitation-emission matrix spectra indicated that the HI fraction contained humic acid-like substances that reacted with chlorine to form THMs. The HON fraction contained soluble microbial byproduct-like substances with a higher potential to create HAAs. The results of Fourier transform infrared (FT-IR) spectroscopy, X-ray photoelectron spectroscopy (XPS), and high-pressure size exclusion chromatography (HP-SEC) of the raw and coagulated water indicated that a higher molecular weight, α-carbon, COOH, aromatic structures, and polysaccharides were associated with a higher production of disinfection byproducts (DBP). These results elucidate the coagulation efficiencies of EfOM fractions associated with different mechanisms and facilitate the prediction of DBP formation by each fraction based on specific structural characteristics.

Pharmacological Intervention Targeting FAF1 Restores Autophagic Flux for α-Synuclein Degradation in the Brain of a Parkinson's Disease Mouse Model.

α-Synuclein accumulation is implicated in the pathogenesis of neurodegenerative diseases, including Parkinson's disease (PD). Previously, we reported that Fas-associated factor 1 (FAF1), which plays a role in PD pathogenesis, potentiates α-synuclein accumulation through autophagy impairment in dopaminergic neurons. In this study, we show that KM-819, a FAF1-targeting compound, which has completed phase I clinical trials, interferes with α-synuclein accumulation in the mouse brain, as well as in human neuronal cells (SH-SY5Ys). KM-819 suppressed the accumulation of monomeric, oligomeric, and aggregated forms of α-synuclein in neuronal cells. Furthermore, KM-819 restored the turnover rate of α-synuclein in FAF1-overexpressing SH-SY5Y cells, implicating KM-819-mediated reconstitution of the α-synuclein degradative pathway. In addition, KM-819 reconstituted autophagic flux in FAF1-transfected SH-SY5Y cells, also suppressing α-synuclein-induced mitochondrial dysfunction. Moreover, oral administration of KM-819 also interfered with α-synuclein accumulation in the midbrain of mice overexpressing FAF1 via an adeno-associated virus system. Consistently, KM-819 reduced α-synuclein accumulation in both the hippocampus and the midbrain of human A53T α-synuclein transgenic mice. Collectively, these data imply that KM-819 may have therapeutic potential for patients with PD.

Trellis for efficient data and task management in the VA Million Veteran Program.

Biomedical studies have become larger in size and yielded large quantities of data, yet efficient data processing remains a challenge. Here we present Trellis, a cloud-based data and task management framework that completely automates the process from data ingestion to result presentation, while tracking data lineage, facilitating information query, and supporting fault-tolerance and scalability. Using a graph database to coordinate the state of the data processing workflows and a scalable microservice architecture to perform bioinformatics tasks, Trellis has enabled efficient variant calling on 100,000 human genomes collected in the VA Million Veteran Program.

Enzyme Complexes of Ptr4CL and PtrHCT Modulate Co-enzyme A Ligation of Hydroxycinnamic Acids for Monolignol Biosynthesis in Populus trichocarpa.

Co-enzyme A (CoA) ligation of hydroxycinnamic acids by 4-coumaric acid:CoA ligase (4CL) is a critical step in the biosynthesis of monolignols. Perturbation of 4CL activity significantly impacts the lignin content of diverse plant species. In Populus trichocarpa, two well-studied xylem-specific Ptr4CLs (Ptr4CL3 and Ptr4CL5) catalyze the CoA ligation of 4-coumaric acid to 4-coumaroyl-CoA and caffeic acid to caffeoyl-CoA. Subsequently, two 4-hydroxycinnamoyl-CoA:shikimic acid hydroxycinnamoyl transferases (PtrHCT1 and PtrHCT6) mediate the conversion of 4-coumaroyl-CoA to caffeoyl-CoA. Here, we show that the CoA ligation of 4-coumaric and caffeic acids is modulated by Ptr4CL/PtrHCT protein complexes. Downregulation of PtrHCTs reduced Ptr4CL activities in the stem-differentiating xylem (SDX) of transgenic P. trichocarpa. The Ptr4CL/PtrHCT interactions were then validated in vivo using biomolecular fluorescence complementation (BiFC) and protein pull-down assays in P. trichocarpa SDX extracts. Enzyme activity assays using recombinant proteins of Ptr4CL and PtrHCT showed elevated CoA ligation activity for Ptr4CL when supplemented with PtrHCT. Numerical analyses based on an evolutionary computation of the CoA ligation activity estimated the stoichiometry of the protein complex to consist of one Ptr4CL and two PtrHCTs, which was experimentally confirmed by chemical cross-linking using SDX plant protein extracts and recombinant proteins. Based on these results, we propose that Ptr4CL/PtrHCT complexes modulate the metabolic flux of CoA ligation for monolignol biosynthesis during wood formation in P. trichocarpa.

Common and rare variant analyses combined with single-cell multiomics reveal cell-type-specific molecular mechanisms of COVID-19 severity.

The determinants of severe COVID-19 in non-elderly adults are poorly understood, which limits opportunities for early intervention and treatment. Here we present novel machine learning frameworks for identifying common and rare disease-associated genetic variation, which outperform conventional approaches. By integrating single-cell multiomics profiling of human lungs to link genetic signals to cell-type-specific functions, we have discovered and validated over 1,000 risk genes underlying severe COVID-19 across 19 cell types. Identified risk genes are overexpressed in healthy lungs but relatively downregulated in severely diseased lungs. Genetic risk for severe COVID-19, within both common and rare variants, is particularly enriched in natural killer (NK) cells, which places these immune cells upstream in the pathogenesis of severe disease. Mendelian randomization indicates that failed NKG2D-mediated activation of NK cells leads to critical illness. Network analysis further links multiple pathways associated with NK cell activation, including type-I-interferon-mediated signalling, to severe COVID-19. Our rare variant model, PULSE, enables sensitive prediction of severe disease in non-elderly patients based on whole-exome sequencing; individualized predictions are accurate independent of age and sex, and are consistent across multiple populations and cohorts. Risk stratification based on exome sequencing has the potential to facilitate post-exposure prophylaxis in at-risk individuals, potentially based around augmentation of NK cell function. Overall, our study characterizes a comprehensive genetic landscape of COVID-19 severity and provides novel insights into the molecular mechanisms of severe disease, leading to new therapeutic targets and sensitive detection of at-risk individuals.

Down-regulation of Fra a 1.02 in strawberry fruits causes transcriptomic and metabolic changes compatible with an altered defense response.

The strawberry Fra a 1 proteins belong to the class 10 Pathogenesis-Related (PR-10) superfamily. In strawberry, a large number of members have been identified, but only a limited number is expressed in the fruits. In this organ, Fra a 1.01 and Fra a 1.02 are the most abundant Fra proteins in the green and red fruits, respectively, however, their function remains unknown. To know the function of Fra a 1.02 we have generated transgenic lines that silence this gene, and performed metabolomics, RNA-Seq, and hormonal assays. Previous studies associated Fra a 1.02 to strawberry fruit color, but the analysis of anthocyanins in the ripe fruits showed no diminution in their content in the silenced lines. Gene ontology (GO) analysis of the genes differentially expressed indicated that oxidation/reduction was the most represented biological process. Redox state was not apparently altered since no changes were found in ascorbic acid and glutathione (GSH) reduced/oxidized ratio, but GSH content was reduced in the silenced fruits. In addition, a number of glutathione-S-transferases (GST) were down-regulated as result of Fra a 1.02-silencing. Another highly represented GO category was transport which included a number of ABC and MATE transporters. Among the regulatory genes differentially expressed WRKY33.1 and WRKY33.2 were down-regulated, which had previously been assigned a role in strawberry plant defense. A reduced expression of the VQ23 gene and a diminished content of the hormones JA, SA, and IAA were also found. These data might indicate that Fra a 1.02 participates in the defense against pathogens in the ripe strawberry fruits.

Sulfonate Version of OHPAS Linker Has Two Distinct Pathways of Breakdown: Elimination Route Allows Para-Hydroxy-Protected Benzylsulfonate (PHP-BS) to Serve as an Alternative Self-Immolative Group.

Recently we have reported that the ortho-hydroxy-protected aryl sulfate (OHPAS) system can be exploited as a new self-immolative group (SIG) for phenolic payloads. We extended the system to nonphenolic payloads by simply introducing a para-hydroxy benzyl (PHB) spacer. As an additional variation of the system, we explored a benzylsulfonate version of the OHPAS system and found that it has two distinct breakdown pathways, cyclization and 1,4-elimination, the latter of which implies that para-hydroxy-protected (PHP) benzylsulfonate (BS) can also be used as an alternative SIG. The PHP-BS system was found to be stable chemically and in mouse and human plasma, having payload release rates comparable to those of the original OHPAS conjugates.

Preferential binding properties of carboxyl and hydroxyl groups with aluminium salts for humic acid removal.

To systematically elucidate the removal characteristics of humic acid (HA), which are highly dependent on the molecular structure of HA, a series of representative HA model compounds containing different numbers and positions of carboxyl and hydroxyl groups were selected, and the chemical reaction behaviour between HA and aluminium coagulants was investigated. The results indicated that the number of carboxyl groups in the benzene ring and binding environment had great effects on the Al-binding properties of HA molecules. Under weakly acidic conditions, coordination occurred between carboxyl and Al ions, and the complexing capacity was restricted by the substituted position of hydroxyl groups. Under neutral conditions or at higher coagulant dosages, sweep coagulation occurred by surface complexation of aluminium hydroxide by carboxyl groups and hydrogen bonding between the hydroxyl group and aluminium hydroxide; this process was dependent on the substitutive pattern of the functional groups. Moreover, increased aliphatic chain length and benzene ring size could enhance hydrophobicity, and hence resulted in higher coagulation efficiency. This study provided new insight into the mechanism of the interaction between HA and aluminium coagulants.

Tracking the reactivity of ozonation towards effluent organic matters from WWTP using two-dimensional correlation spectra.

The characteristics of effluent organic matter (EfOM) from a wastewater treatment plant (WWTP) during ozonation were investigated using excitation and emission matrix (EEM) spectra, Fourier transform infrared spectroscopy (FT-IR) and high-performance size exclusion chromatography (HPSEC) at different ozone dosages. The selectivity of ozonation towards different constituents and functional groups was analysed using two-dimensional correlation spectra (2D-COS) probed by FT-IR, synchronous fluorescence spectra and HPSEC. The results indicated that ozonation can destroy aromatic structures of EfOM and change its molecular weight distribution (MWD). According to 2D-COS analysis, microbial humic-like substances were preferentially removed, and then the protein-like fractions. Terrestrial humic-like components exhibited inactivity towards ozonation compared with the above two fractions. Protein-like substances with small molecular weight were preferentially reacted during ozonation based on 2D-COS probed by HPSEC. In addition, the selectivity of ozone towards different functional groups of EfOM exhibited the following sequence: phenolic and alcoholic CO groups > aromatic structures containing CC double bonds > aliphatic CH. X-ray photoelectron spectroscopy (XPS) further elucidated the preferential reaction of aromatic structures in EfOM during ozonation.

Synergistic effects of various in situ hydrolyzed aluminum species for the removal of humic acid.

Due to the diversity of in situ hydrolyzed aluminum species and discrepancy in the binding sites of humic acid (HA), the mechanisms involved in HA removal were significantly different in inorganic particle removal. Based on the background, the coagulation behavior of in situ and performed hydrolyzed aluminum species for the removal of HA was investigated. For AlCl3, the maximum HA removal reached at weak acidic conditions, where various in situ hydrolyzed Al species containing Al1 to Al20 cores with different amounts of water molecules were present. Various Al species could meet the demand for different binding sites and enhance the complexing probability for weak binding sites. Meanwhile, most of the binding sites are occupied by the aluminum ion, which brought about better complexation capacity with the Al species. Therefore, the synergistic effects of various in situ hydrolyzed aluminum species played important roles in the removal of HA. Compared with AlCl3, preformed Al13 had less efficient in HA removal because the Zeta potential of HA formed by preformed Al13 with uniform Al species increased from negative to positive with increase in Al13 dosage. This study provided new insight into the interaction between HA and various hydrolyzed Al species.

Apolipoprotein A-IV binds αIIbß3 integrin and inhibits thrombosis.

Platelet αIIbß3 integrin and its ligands are essential for thrombosis and hemostasis, and play key roles in myocardial infarction and stroke. Here we show that apolipoprotein A-IV (apoA-IV) can be isolated from human blood plasma using platelet ß3 integrin-coated beads. Binding of apoA-IV to platelets requires activation of αIIbß3 integrin, and the direct apoA-IV-αIIbß3 interaction can be detected using a single-molecule Biomembrane Force Probe. We identify that aspartic acids 5 and 13 at the N-terminus of apoA-IV are required for binding to αIIbß3 integrin, which is additionally modulated by apoA-IV C-terminus via intra-molecular interactions. ApoA-IV inhibits platelet aggregation and postprandial platelet hyperactivity. Human apoA-IV plasma levels show a circadian rhythm that negatively correlates with platelet aggregation and cardiovascular events. Thus, we identify apoA-IV as a novel ligand of αIIbß3 integrin and an endogenous inhibitor of thrombosis, establishing a link between lipoprotein metabolism and cardiovascular diseases.

Pinosylvin enhances leukemia cell death via down-regulation of AMPKα expression.

Resveratrol at high concentrations (50-100 µmol/L) is known to induce cell death in leukemia cells. Here, we investigated whether pinosylvin, a resveratrol analogue, induced cell death in leukemia cells. Cell death was found to be markedly elevated by 50- to 100-µmol/L pinosylvin in THP-1 and U937 cells. It was also shown that pinosylvin induced caspase-3 activation, flip-flop of phosphatidylserine, LC3-II accumulation, LC3 puncta, and p62 degradation in both THP-1 and U937 cells. These data indicate that pinosylvin-induced cell death may occur through apoptosis and autophagy. In addition, we showed that pinosylvin down-regulates AMP-activated protein kinase α1 (AMPKα1) in leukemia cells. Therefore, we correlated AMPKα1 down-regulation and leukemia cell death. AMPKα1 inhibition appeared to decrease pinosylvin-induced apoptosis and autophagy in leukemia cells, implying that AMPK is a key regulator of leukemia cell death. Moreover, we found that both pinosylvin-induced autophagy and apoptotic progress were reduced in AMPKα1-overexpressed leukemia cells, when compared with vector-transfected cells. Cell death was elevated by AMPKα1 overexpression, whereas pinosylvin-induced cell death was markedly decreased by caspase-3 inhibitors or autophagy inhibitors. These results suggest that pinosylvin-induced depletion of AMPKα1 enhances cell death via apoptosis and autophagy in leukemia cells.

Improving wood properties for wood utilization through multi-omics integration in lignin biosynthesis.

A multi-omics quantitative integrative analysis of lignin biosynthesis can advance the strategic engineering of wood for timber, pulp, and biofuels. Lignin is polymerized from three monomers (monolignols) produced by a grid-like pathway. The pathway in wood formation of Populus trichocarpa has at least 21 genes, encoding enzymes that mediate 37 reactions on 24 metabolites, leading to lignin and affecting wood properties. We perturb these 21 pathway genes and integrate transcriptomic, proteomic, fluxomic and phenomic data from 221 lines selected from ~2000 transgenics (6-month-old). The integrative analysis estimates how changing expression of pathway gene or gene combination affects protein abundance, metabolic-flux, metabolite concentrations, and 25 wood traits, including lignin, tree-growth, density, strength, and saccharification. The analysis then predicts improvements in any of these 25 traits individually or in combinations, through engineering expression of specific monolignol genes. The analysis may lead to greater understanding of other pathways for improved growth and adaptation.

Two-dimensional correlation spectroscopic analysis on the interaction between humic acids and aluminum coagulant.

In this study, two-dimensional correlation spectroscopy integrated with synchronous fluorescence and infrared absorption spectroscopy was employed to investigate the interaction between humic acids and aluminum coagulant at slightly acidic and neutral pH. Higher fluorescence quenching was produced for fulvic-like and humic-like fractions at pH5. At pH5, the humic-like fractions originating from the carboxylic acid, carboxyl and polysaccharide compounds were bound to aluminum first, followed by the fulvic-like fractions originating from the carboxyl and polysaccharide compounds. This finding also demonstrated that the activated functional groups of HA were involved in forming the Al-HA complex, which was accompanied by the removal of other groups by co-precipitation. Meanwhile, at pH7, almost no fluorescence quenching occurred, and surface complexation was observed to occur, in which the activated functional groups were absorbed on the amorphous Al(OH)3. Two-dimensional FT-IR correlation spectroscopy indicated the sequence of HA structural change during coagulation with aluminum, with IR bands affected in the order of COOH>COO->NH deformation of amide II>aliphatic hydroxyl COH at pH5, and COO->aliphatic hydroxyl COH at pH7. This study provides a promising pathway for analysis and insight into the priority of functional groups in the interaction between organic matters and metal coagulants.