MoS2@MWCNTs with Rich Vacancy Defects for Effective Piezocatalytic Degradation of Norfloxacin via Innergenerated-H2O2: Enhanced Nonradical Pathway and Synergistic Mechanism with Radical Pathway.

Molybdenum disulfide (MoS2)-based materials for piezocatalysis are unsatisfactory due to their low actual piezoelectric coefficient and poor electrical conductivity. Herein, 1T/3R phase MoS2 grown in situ on multiwalled carbon nanotubes (MWCNTs) was proposed. MoS2@MWCNTs exhibited the interwoven morphology of thin nanoflowers and tubes, and the piezoelectric response of MoS2@MWCNTs was 4.07 times higher than that of MoS2 via piezoresponse force microscopy (PFM) characterization. MoS2@MWCNTs exhibited superior activity with a 91% degradation rate of norfloxacin (NOR) after actually working 24 min (as for rhodamine B, reached 100% within 18 min) by pulse-mode ultrasonic vibration-triggered piezocatalysis. It was found that piezocatalysis for removing pollutants was attributed to the synergistic effect of free radicals (•OH and O2•-) and nonfree radical (1O2, key role) pathways, together with the innergenerated-H2O2 promoting the degradation rate. 1O2 can be generated by electron transfer and energy transfer pathways. The presence of oxygen vacancies (OVs) induced the transformation of O2 to 1O2 by triplet energy transfer. The fast charge transfer in MoS2@MWCNTs heterostructure and the coexistence of sulfur vacancies and OVs enhanced charge carrier separation resulting in a prominent piezoelectric effect. This work opens up new avenues for the development of efficient piezocatalysts that can be utilized for environmental purification.

Combined gestational age and serum fucose for early prediction of risk for bronchopulmonary dysplasia in premature infants.

OBJECTIVE: As the predominant complication in preterm infants, Bronchopulmonary Dysplasia (BPD) necessitates accurate identification of infants at risk and expedited therapeutic interventions for an improved prognosis. This study evaluates the potential of Monosaccharide Composite (MC) enriched with environmental information from circulating glycans as a diagnostic biomarker for early-onset BPD, and, concurrently, appraises BPD risk in premature neonates. MATERIALS AND METHODS: The study incorporated 234 neonates of ≤32 weeks gestational age. Clinical data and serum samples, collected one week post-birth, were meticulously assessed. The quantification of serum-free monosaccharides and their degraded counterparts was accomplished via High-performance Liquid Chromatography (HPLC). Logistic regression analysis facilitated the construction of models for early BPD diagnosis. The diagnostic potential of various monosaccharides for BPD was determined using Receiver Operating Characteristic (ROC) curves, integrating clinical data for enhanced diagnostic precision, and evaluated by the Area Under the Curve (AUC). RESULTS: Among the 234 neonates deemed eligible, BPD development was noted in 68 (29.06%), with 70.59% mild (48/68) and 29.41% moderate-severe (20/68) cases. Multivariate analysis delineated several significant risk factors for BPD, including gestational age, birth weight, duration of both invasive mechanical and non-invasive ventilation, Patent Ductus Arteriosus (PDA), pregnancy-induced hypertension, and concentrations of two free monosaccharides (Glc-F and Man-F) and five degraded monosaccharides (Fuc-D, GalN-D, Glc-D, and Man-D). Notably, the concentrations of Glc-D and Fuc-D in the moderate-to-severe BPD group were significantly diminished relative to the mild BPD group. A potent predictive capability for BPD development was exhibited by the conjunction of gestational age and Fuc-D, with an AUC of 0.96. CONCLUSION: A predictive model harnessing the power of gestational age and Fuc-D demonstrates promising efficacy in foretelling BPD development with high sensitivity (95.0%) and specificity (94.81%), potentially enabling timely intervention and improved neonatal outcomes.

Underestimated health risks: Dietary restriction magnify the intestinal barrier dysfunction and liver injury in mice induced by polystyrene microplastics.

Microplastics (MPs) have gained significant attention due to their widespread presence in the environment. While studies have been conducted to investigate the risks associated with MPs, the potential effects of MPs on populations with varying dietary habits, such as dietary restriction (DR), remain largely undefined. The sensitivity of the body to invasive contaminants may increase due to insufficient food intake. Here, we aimed to investigate whether dietary restriction could affect the toxicity of MPs in mice. Following a 5-week exposure to 200 µg/L polystyrene microplastics (PSMPs), DR-PSMPs treatment group exhibited significant intestinal barrier dysfunction compared to ND-PSMPs treatment group, as determined by histopathological and biochemical analysis. Dietary restriction worsened liver oxidative stress and bile acid disorder in mice exposed to PSMPs. 16S rRNA sequencing analysis revealed that DR-PSMPs treatment caused alterations in gut microbiota composition, including the downregulation of probiotics abundance and upregulation of pathogenic bacteria abundance. The negative effects caused by PSMPs in mice with dietary restriction could attribute to increased MPs bioaccumulation, declined water intake, reduced probiotics abundance, and elevated pathogenic bacteria abundance, as well as the susceptibility of the dietary restriction individual. Our findings hint that the biological effects of contaminants could be affected by dietary habits.

LINC01116 Regulates the Proliferation and Apoptosis of Nucleus Pulposus Cells through miR-9-5p-mediated ZIC5 and the Wnt Pathway and Affects the Progression of Intervertebral Disc Degeneration.

OBJECTIVE: Intervertebral disc degeneration (IDD) represents one of the leading causes of low back pain. Research suggests the participation of LINC01116 in IDD progression. Herein, the current study explored the underlying mechanism of LINC01116 in IDD. METHODS: The differential expression patterns of LINC01116 in IDD and normal tissues were analyzed using the GEO database. Human nucleus pulposus (NP) cells were provided and treated with IL-1ß to establish IDD models in vitro. LINC01116 expression was detected and intervened. Indices such as cell proliferation, apoptosis, and extracellular matrix (ECM)-related factor expression were determined using CCK-8 assay, flow cytometry, and Western blotting. LINC01116 sublocation was identified by means of nuclear/cytosol fractionation assay. The binding relationships between LINC01116 and miR-9-5p and miR-9-5p and ZIC5 were verified by bioinformatics analysis, dual-luciferase assays, RNA immunoprecipitation (RIP) assay, and RNA-pull-down. Western blotting was conducted to measure the levels of the Wnt pathway key factors. RESULTS AND DISCUSSION: LINC01116 was highly expressed in the degenerative NP cells. Silencing of LINC01116 critically promoted degenerative NP cell proliferation and inhibited apoptosis and ECM loss. LINC01116 was located in the cytoplasm. In degenerative NP cell models, LINC01116 could competitively bind to miR-9-5p to elevate ZIC5 expression. LINC01116 induced NP cell apoptosis and impeded NP cell proliferation and ECM synthesis by inhibiting miR-9-5p and miR-9-5p targeted ZIC5. ZIC5 could effectively increase the levels of the Wnt pathway-related factors. CONCLUSION: Silencing LINC01116 blocked its adsorption of miR-9-5p as a sponge to promote the miR-9- 5p expression and inhibit ZIC5/Wnt activation, thus impacting NP cell biological functions.

A comparative study in healthy and diabetic mice followed the exposure of polystyrene microplastics: Differential lipid metabolism and inflammation reaction.

Human exposure to microplastics (MPs) continues to occur due to ingestion of contaminated food, water and air. Intake of MPs can pose potential health risks by interfering with the production and circulation of nutrients, leading to physiological stress (such as immune responses and metabolic abnormalities). Toxicity data of MPs based on healthy individuals may not be applicable to large populations of patients with chronic diseases represented by diabetes. Therefore, in this study, the response of diabetic mice was compared with that of healthy mice after exposure to polystyrene microplastics (PS-MPs), and interesting differences were observed. PS-MPs exposure significantly increased liver tissue damage, abnormal lipid metabolism, inflammatory effect, liver metabolic disorder and changes of intestinal microbial composition in diabetic mice. Moreover, PS-MPs overstated abnormal lipid metabolism in diabetic mice. The difference between the increased inflammation after exposure to PS-MPs in healthy and diabetic mice involves that the former is mainly modulated by gut microbes, while diabetic mice seem to be more susceptible to lipid metabolism disturbances. In addition, the size effect of MPs was also observed in diabetic mice. These results suggested that individuals with chronic diseases may be more sensitive to pollution due to altered homeostasis, and therefore disease status should be fully considered when assessing the health risk of pollutants.

MiR-98 Protects Nucleus Pulposus Cells against Apoptosis by Targeting TRAIL in Cervical Intervertebral Disc Degeneration.

The excessive apoptosis of nucleus pulposus (NP) cells is a major risk factor in the progress of cervical intervertebral disc degeneration (IVDD). In this study, we investigated the impact of miR-98 on apoptosis of NP cells and the potential molecular mechanisms. Lipopolysaccharide (LPS) was used to establish an NP cell IVDD model. The sponging effect of miR-98 on TRAIL 3'UTR was predicted by ENCORI and assessed by the dual-luciferase reporter gene system. The expression levels of miR-98, TRAIL, and TRAIL pathway-related genes were tested by qRT-PCR, Western blot, and immunofluorescence analysis. Cell apoptosis was analyzed by Hoechst 33258 staining and flow cytometry. Cell viability was analyzed by MTT assay. It was found that the expression level of miR-98 was downregulated, while the level of TRAIL was upregulated in IVDD tissues, and their levels were negatively and positively associated with the clinical MRI grade, respectively. The LPS treatment resulted in a significant decrease of the miR-98 expression level and an increase of the TRAIL expression level in NP cells. miR-98 reduced NP cell apoptosis under LPS treatment in vitro. miR-98 directly targeted TRAIL. Moreover, the mRNA and protein levels of DR5, FADD, cleaved caspase8, cleaved caspase3, and cleaved PARP were downregulated by miR-98 overexpression. Overexpression of TRAIL partially reversed the suppressive roles of miR-98 on cell apoptosis and activation of the TRAIL pathway. We concluded that miR-98 inhibited apoptosis of NP cells by inactivating the TRAIL pathway via targeting TRAIL in IVDD NP cells. These results indicated that miR-98 might be a therapeutic target for IVDD.

Discovery of novel N-1 substituted pyrazolopyrimidinones as potent, selective PDE2 inhibitors.

A focused SAR study was conducted on a series of N1-substituted pyrazolopyrimidinone PDE2 inhibitors to reveal compounds with excellent potency and selectivity. The series was derived from previously identified internal leads and designed to enhance steric interactions with key amino acids in the PDE2 binding pocket. Compound 26 was identified as a lead compound with excellent PDE2 selectivity and good physicochemical properties.

GmbZIP1 negatively regulates ABA-induced inhibition of nodulation by targeting GmENOD40-1 in soybean.

BACKGROUND: Abscisic acid (ABA) plays an important role in plant growth and adaptation through the ABA signaling pathway. The ABA-responsive element binding (AREB/ABF) family transcriptional factors are central regulators that integrate ABA signaling with various signaling pathways. It has long been known that ABA inhibits rhizobial infection and nodule formation in legumes, but the underlying molecular mechanisms remain elusive. RESULTS: Here, we show that nodulation is very sensitive to ABA and exogenous ABA dramatically inhibits rhizobial infection and nodule formation in soybean. In addition, we proved that GmbZIP1, an AREB/ABF transcription factor, is a major regulator in both nodulation and plant response to ABA in soybean. GmbZIP1 was specifically expressed during nodule formation and development. Overexpression of GmbZIP1 resulted in reduced rhizobial infection and decreased nodule number. Furthermore, GmbZIP1 is responsive to ABA, and ectopic overexpression of GmbZIP1 increased sensitivity of Arabidopsis plants to ABA during seed germination and postgerminative growth, and conferred enhanced drought tolerance of plants. Remarkably, we found that GmbZIP1 directly binds to the promoter of GmENOD40-1, a marker gene for nodule formation, to repress its expression. CONCLUSION: Our results identified GmbZIP1 as a node regulator that integrates ABA signaling with nodulation signaling to negatively regulate nodule formation.

Kinetic Analysis for Reaction of Cyclopentadiene with Hydroperoxyl Radical under Low- and Medium-Temperature Combustion.

The kinetic data of cyclopentadiene C5H6 oxidation reactions are significant for the construction of aromatics oxidation mechanism because cyclopentadiene C5H6 has been proved to be an important intermediate in the aromatics combustion. Kinetics for the elementary reactions on the potential energy surface (PES) relevant for the C5H6 + HO2 reaction are studied in this work. Stationary points on the PES are calculated by employing the CCSD(T)/cc-pVTZ//B3LYP/6-311G(d,p) level of theory. High-pressure limit and pressure-dependent rate constants for elementary reactions on this PES are calculated using conventional transition state theory (TST), variational transition-state theory (VTST) and Rice-Ramsberger-Kassel-Marcus/master equation (RRKM/ME) theory. In this work, the reaction channels for the C5H6 + HO2 reaction, which include H-abstraction channels from C5H6 by HO2 to form the C5H5 + H2O2 and the addition channels through well-skipping pathways to form the bimolecular products C5H7 + O2 or C5H6O + OH, or through C5H7O2 stabilization and its unimolecular decomposition to form the bimolecular products C5H7 + O2 or C5H6O + OH, namely sequential pathways, are studied. Also, the consuming reaction channels for the compounds C5H6O and C5H7 in the addition products are studied. The dominant reaction channels for these reactions are unraveled through comparing the energy barriers and rate constants of all elementary reactions and it is found: (1) HO2 addition to cyclopentadiene C5H6 is more important than direct H-abstraction. (2) in the HO2 addition channels, the well-skipping pathways and sequential pathways are competing and the well-skipping pathways will be favor in the higher pressures and the sequential pathways will be favor in the higher temperature. (3) The major consumption reaction channel for the five-member-ring compound C5H6O is the reaction channel to form C4H6 + CO and the major consumption reaction channel for the five-member-ring compound C5H7 is the reaction channel to form C3H5 + C2H2. High-pressure limit rate constants and pressure-dependent rate constants for elementary reactions on the PES are calculated, which will be useful in modeling the oxidation of aromatic compounds at low- and medium-temperatures.

Counteraction of ABA-Mediated Inhibition of Seed Germination and Seedling Establishment by ABA Signaling Terminator in Arabidopsis.

Seed germination and seedling establishment are important for the reproductive success of plants, but seeds and seedlings typically encounter constantly changing environmental conditions. By inhibiting seed germination and post-germinative growth through the PYR1/PYL/RCAR ABA receptors and PP2C co-receptors, the phytohormone abscisic acid (ABA) prevents premature germination and seedling growth under unfavorable conditions. However, little is known about how the ABA-mediated inhibition of seed germination and seedling establishment is thwarted. Here, we report that ABA Signaling Terminator (ABT), a WD40 protein, efficiently switches off ABA signaling and is critical for seed germination and seedling establishment. ABT is induced by ABA in a PYR1/PYL/RCAR-PP2C-dependent manner. Overexpression of ABT promotes seed germination and seedling greening in the presence of ABA, whereas knockout of ABT has the opposite effect. We found that ABT interacts with the PYR1/PYL/RCAR and PP2C proteins, interferes with the interaction between PYR1/PYL4 and ABI1/ABI2, and hampers the inhibition of ABI1/ABI2 by ABA-bound PYR1/PYL4, thereby terminating ABA signaling. Taken together, our results reveal a core mechanism of ABA signaling termination that is critical for seed germination and seedling establishment in Arabidopsis.

GAI Functions in the Plant Response to Dehydration Stress in Arabidopsis thaliana.

DELLA (GAI/RGA/RGL1/RGL2/RGL3) proteins are key negative regulators in GA (gibberellin) signaling and are involved in regulating plant growth as a response to environmental stresses. It has been shown that the DELLA protein PROCERA (PRO) in tomato promotes drought tolerance, but its molecular mechanism remains unknown. Here, we showed that the gai-1 (gibberellin insensitive 1) mutant (generated from the gai-1 (Ler) allele (with a 17 amino acid deletion within the DELLA domain of GAI) by backcrossing gai-1 (Ler) with Col-0 three times), the gain-of-function mutant of GAI (GA INSENSITIVE) in Arabidopsis, increases drought tolerance. The stomatal density of the gai-1 mutant was increased but its stomatal aperture was decreased under abscisic acid (ABA) treatment conditions, suggesting that the drought tolerance of the gai-1 mutant is a complex trait. We further tested the interactions between DELLA proteins and ABF2 (abscisic acid (ABA)-responsive element (ABRE)-binding transcription factors) and found that there was a strong interaction between DELLA proteins and ABF2. Our results provide new insight into DELLA proteins and their role in drought stress tolerance.

Comparative Study of Single Molecular Junctions with Para-Phthalic Acid and Meta-Phthalic Acid Binding to Different Metal Electrodes.

In this paper, single molecular junctions of Para-phthalic acid and Meta-phthalic acid with Au electrodes were studied by STM break junction approach. Conductance values of 10-3.55 G0 and 10-3.70 G0 were found for Para-phthalic acid and Meta-phthalic acid, respectively. The conductance order between Para-phthalic acid and Meta-phthalic acid with Au is different from that with Cu, which can be contributed to the different coupling between molecules and electrodes; different through-space interaction is proposed for such phenomenon between Cu and Au electrodes. Furthermore, the breaking off distances can reflect the length of molecules. The current work presents the important role of electrode in single molecular junctions with different position anchoring groups.

Clinical observation of the application of autologous peripheral blood stem cell transplantation for the treatment of diabetic foot gangrene.

The aim of the present study was to investigate the optimal mobilization plan in autologous peripheral blood stem cell transplantation for the treatment of diabetic foot and to observe its clinical curative effect. A total of 127 patients with diabetic foot were treated with different doses of granulocyte colony stimulating factor (G-CSF) to mobilize their hematopoietic stem cells. Subsequently, the extracted stem cell suspension was injected into the ischemic lower extremities along the blood vessels in the areas presenting with pathological changes. Following the treatment, the intermittent claudication distance, skin temperature, ankle brachial index and pain scores of the patients were evaluated. In addition, the associations among the mobilization time, doses and peripheral blood CD34+ level were analyzed. The collection efficiency of the stem cells was associated with the dose of G-CSF and the mobilization time. Following the injection of the autologous peripheral blood stem cell suspension, the ischemic area of the patients was improved significantly. In conclusion, autologous peripheral blood stem cell transplantation can promote the establishment of collateral circulation in patients with diabetic foot, and the optimal time for gathering stem cells is closely correlated with the peripheral blood CD34+ level.

Correlation between Polymorphism of TRAIL Gene and Condition of Intervertebral Disc Degeneration.

BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been suggested to be related with the pathogenesis and progression of osteoarticular degenerations. This study therefore aimed to investigate the relationship between the polymorphism of the TRAIL gene and the pathogenesis and severity of intervertebral disc degeneration (IDD) via detection of serum TRAIL expression levels. MATERIAL AND METHODS: A total of 100 IDD patients in our hospital were recruited in the experimental group, while another cohort of 100 healthy individuals was employed as the control group. Blood samples collected from all people were quantified for TRAIL level using enzyme-linked immunosorbent assay (ELISA), in addition to allele and genotype frequency analysis via fluorescent PCR for TRAIL gene. RESULTS: At loci 1525 and 1529 in 3'-untranslated region (UTR) of 5th exon of TRAIL gene, 3 different genotypes were identified: experimental group had higher frequency of 1525CG/1595CC, 1525G and 1595C alleles, compared to the control group (p<0.05). Patients under Schneiderman grade IV had significantly higher allele frequency compared to those at grade II or III. Serum TRAIL level was also higher in the experimental group compared to the control group, and in grade IV patients compared to grade II or III patients (p<0.05). CONCLUSIONS: The G/C mutation at loci 1525/1595 of TRAIL gene may induce the progression of IDD, as the down-regulation of TRAIL can aggravate the severity of the disease.

Discovery and optimization of a highly efficacious class of 5-aryl-2-aminopyridines as FMS-like tyrosine kinase 3 (FLT3) inhibitors.

Based on a putative binding mode of quizartinib (AC220, 1), a potent FMS-like tyrosine kinase 3 (FLT3) inhibitor in Phase III clinical development, we have designed de novo a simpler aminopyridine-based hinge binding motif. Further optimization focusing on maximizing in vivo efficacy and minimizing CYP3A4 time-dependent inhibition resulted in a highly efficacious compound (6s) in tumor xenograft model for further preclinical development.

Synthesis of polyfunctionalized quinolines via the sequence of propargyl-allenyl isomerization and aza-electrocyclization.

Quinoline derivatives are important heterocyclic compounds because of their natural occurrence and applications in pharmaceutical fields. In this paper, a sequence of propargyl-allenyl isomerization and aza-electrocyclization for the synthesis of polyfunctionalized quinolines are described.

Discovery of highly potent and selective pan-Aurora kinase inhibitors with enhanced in vivo antitumor therapeutic index.

Serine/threonine protein kinases Aurora A, B, and C play essential roles in cell mitosis and cytokinesis. Currently a number of Aurora kinase inhibitors with different isoform selectivities are being evaluated in the clinic. Herein we report the discovery and characterization of 21c (AC014) and 21i (AC081), two structurally novel, potent, kinome-selective pan-Aurora inhibitors. In the human colon cancer cell line HCT-116, both compounds potently inhibit histone H3 phosphorylation and cell proliferation while inducing 8N polyploidy. Both compounds administered intravenously on intermittent schedules displayed potent and durable antitumor activity in a nude rat HCT-116 tumor xenograft model and exhibited good in vivo tolerability. Taken together, these data support further development of both 21c and 21i as potential therapeutic agents for the treatment of solid tumors and hematological malignancies.

Discovery and evaluation of 7-alkyl-1,5-bis-aryl-pyrazolopyridinones as highly potent, selective, and orally efficacious inhibitors of p38alpha mitogen-activated protein kinase.

The p38alpha mitogen-activated protein (MAP) kinase is a central signaling molecule in many proinflammatory pathways, regulating the cellular response to a multitude of external stimuli including heat, ultraviolet radiation, osmotic shock, and a variety of cytokines especially interleukin-1beta and tumor necrosis factor alpha. Thus, inhibitors of this enzyme are postulated to have significant therapeutic potential for the treatment of rheumatoid arthritis, inflammatory bowel disease, and Crohn's disease, as well as other diseases where aberrant cytokine signaling is the driver of disease. In this communication, we describe a novel class of 7-alkyl-1,5-bis-aryl-pyrazolopyridinone-based p38alpha inhibitors. In particular, compound 3f is highly potent in the enzyme and cell-based assays, selective in an Ambit kinase screen, and efficacious (ED(50) < or = 0.01 mg/kg) in the rat collagen induced arthritis (CIA) model.

Separation of ethanol/water azeotrope using compound starch-based adsorbents.

Comparing breakthrough cures of five starch-based materials experimentally prepared for ethanol dehydration, a compound adsorptive agent ZSG-1 was formulated with high adsorption capacity, low energy and material cost. The selective water adsorption was conducted in a fixed-bed absorber packed with ZSG-1 to find the optimum conditions yielding 99.7 wt% anhydrous ethanol with high efficiency. The adsorption kinetics is well described by Bohart-Adams equation. The adsorption heat, Delta H(abs), was calculated to be -3.16 x 10(4)J mol(-1) from retention data by inverse gas chromatography. Results suggested that water entrapment in ZSG-1 is a exothermic and physisorption process. Also, ZSG-1 is recyclable for on-site multiple-use and then adapt for upstream fermentation process after saturation, avoiding pollution through disposal.

Preparation and characterization of molecular weight fractions of glycosaminoglycan from sea cucumber Thelenata ananas using free radical depolymerization.

A glycosaminoglycan from sea cucumber Thelenata anana (THG) was isolated as a polymer of molecular weight of around 70 kDa. Its low molecular weight derivatives were first prepared by free radical depolymerization with hydrogen peroxide in the presence of copper(II) ion. The parameters of the process were investigated by a high-performance gel permeation chromatography. Analyses of chemical composition and molecular weight distribution indicated that the fragmentation of the main-chain of THG occurred randomly, obeyed pseudo first-order kinetics, and produced species with rather narrow and unimodal distribution of molar mass. The characterization of different molecular weight fractions was investigated by using viscometry and atomic force microscopy (AFM). Analysis of molecular weight and intrinsic viscosity in terms of the known theories for unperturbed wormlike cylinder yielded 1201+/-110 nm(-1), 15.3+/-1.5 nm, and 1.5+/-0.3 nm for molar mass per unit contour length M(L), persistence length q, and diameter d, respectively. The M(L) and d values were approximately consistent with those observed by AFM. The present data suggest that THG may dissolve in 0.1M aqueous NaCl as single-stranded helical chains.