D-histidine combated biofilm formation and enhanced the effect of amikacin against Pseudomonas aeruginosa in vitro.

Pseudomonas aeruginosa is an opportunistic gram-negative pathogenic microorganism that poses a significant challenge in clinical treatment. Antibiotics exhibit limited efficacy against mature biofilm, culminating in an increase in the number of antibiotic-resistant strains. Therefore, novel strategies are essential to enhance the effectiveness of antibiotics against Pseudomonas aeruginosa biofilms. D-histidine has been previously identified as a prospective anti-biofilm agent. However, limited attention has been directed towards its impact on Pseudomonas aeruginosa. Therefore, this study was undertaken to explore the effect of D-histidine on Pseudomonas aeruginosa in vitro. Our results demonstrated that D-histidine downregulated the mRNA expression of virulence and quorum sensing (QS)-associated genes in Pseudomonas aeruginosa PAO1 without affecting bacterial growth. Swarming and swimming motility tests revealed that D-histidine significantly reduced the motility and pathogenicity of PAO1. Moreover, crystal violet staining and confocal laser scanning microscopy demonstrated that D-histidine inhibited biofilm formation and triggered the disassembly of mature biofilms. Notably, D-histidine increased the susceptibility of PAO1 to amikacin compared to that in the amikacin-alone group. These findings underscore the efficacy of D-histidine in combating Pseudomonas aeruginosa by reducing biofilm formation and increasing biofilm disassembly. Moreover, the combination of amikacin and D-histidine induced a synergistic effect against Pseudomonas aeruginosa biofilms, suggesting the potential utility of D-histidine as a preventive strategy against biofilm-associated infections caused by Pseudomonas aeruginosa.

In Situ Infrared Spectroscopic Evidence of Enhanced Electrochemical CO2 Reduction and C-C Coupling on Oxide-Derived Copper.

The reaction mechanism of CO2 electroreduction on oxide-derived copper has not yet been unraveled even though high C2+ Faradaic efficiencies are commonly observed on these surfaces. In this study, we aim to explore the effects of copper anodization on the adsorption of various CO2RR intermediates using in situ surface-enhanced infrared absorption spectroscopy (SEIRAS) on metallic and mildly anodized copper thin films. The in situ SEIRAS results show that the preoxidation process can significantly improve the overall CO2 reduction activity by (1) enhancing CO2 activation, (2) increasing CO uptake, and (3) promoting C-C coupling. First, the strong *COO- redshift indicates that the preoxidation process significantly enhances the first elementary step of CO2 adsorption and activation. The rapid uptake of adsorbed *COatop also illustrates how a high *CO coverage can be achieved in oxide-derived copper electrocatalysts. Finally, for the first time, we observed the formation of the *COCHO dimer on the anodized copper thin film. Using DFT calculations, we show how the presence of subsurface oxygen within the Cu lattice can improve the thermodynamics of C2 product formation via the coupling of adsorbed *CO and *CHO intermediates. This study advances our understanding of the role of surface and subsurface conditions in improving the catalytic reaction kinetics and product selectivity of CO2 reduction.

Targeting proteasomal deubiquitinases USP14 and UCHL5 with b-AP15 reduces 5-fluorouracil resistance in colorectal cancer cells.

5-Fluorouracil (5-FU) is the first-line treatment for colorectal cancer (CRC) patients, but the development of acquired resistance to 5-FU remains a big challenge. Deubiquitinases play a key role in the protein degradation pathway, which is involved in cancer development and chemotherapy resistance. In this study, we investigated the effects of targeted inhibition of the proteasomal deubiquitinases USP14 and UCHL5 on the development of CRC and resistance to 5-FU. By analyzing GEO datasets, we found that the mRNA expression levels of USP14 and UCHL5 in CRC tissues were significantly increased, and negatively correlated with the survival of CRC patients. Knockdown of both USP14 and UCHL5 led to increased 5-FU sensitivity in 5-FU-resistant CRC cell lines (RKO-R and HCT-15R), whereas overexpression of USP14 and UCHL5 in 5-FU-sensitive CRC cells decreased 5-FU sensitivity. B-AP15, a specific inhibitor of USP14 and UCHL5, (1-5 µM) dose-dependently inhibited the viability of RKO, RKO-R, HCT-15, and HCT-15R cells. Furthermore, treatment with b-AP15 reduced the malignant phenotype of CRC cells including cell proliferation and migration, and induced cell death in both 5-FU-sensitive and 5-FU-resistant CRC cells by impairing proteasome function and increasing reactive oxygen species (ROS) production. In addition, b-AP15 inhibited the activation of NF-κB pathway, suppressing cell proliferation. In 5-FU-sensitive and 5-FU-resistant CRC xenografts nude mice, administration of b-AP15 (8 mg·kg-1·d-1, intraperitoneal injection) effectively suppressed the growth of both types of tumors. These results demonstrate that USP14 and UCHL5 play an important role in the development of CRC and resistance to 5-FU. Targeting USP14 and UCHL5 with b-AP15 may represent a promising therapeutic strategy for the treatment of CRC.

A dual-cycle regeneration to recover high-value and high-purity FePO4 from real wastewater for Li-battery application.

The recovery of high-purity and high-value FePO4 raw materials from wastewater has great prospects in LiFePO4 battery industry due to the huge demand for new energy vehicle. However, the conventional in-situ FePO4 precipitation, as well as ex-situ PO43- adsorption-alkali regeneration, was incapable of efficiently obtaining high-purity products. To solve these problems, a dual-cycle regeneration method of Fe-NH2-polyacrylonitrile (PAN) adsorbent and H2SO4 desorbing solution was proposed to ex-situ FePO4 recovery from wastewater for Li-battery application. Benefitted from coordination interaction and electrostatic attraction, the maximum PO43- adsorption capacity of Fe-NH2-PAN reached 73.1 ± 0.4 mg/g. The average PO43- removal rate of continuous flow devices were 88.5% and 91.3% when treating low-P-concentration (0.22 mg/L) municipal wastewater (MW) and high-P-concentration (48.9 mg/L) slaughterhouse wastewater (SW) respectively. Furthermore, high-purity FePO4 analyzed by XRD spectra was achieved from the desorption solution at pH ∼1.6, resulting in the ultrahigh P recovery efficiencies of 91.4 ± 3.2%-96.3 ± 2.5% for SW and 82.7 ± 3.5% for MW. Besides, the LiFePO4/C electrodes made of recycled FePO4 exhibited a better discharge capacity (37.3 - 55.8 mAh/g) than that of commercial FePO4 agent (32.2 - 35.1 mAh/g) from 80 to 132 cycles, which showed the promising feasibility of recovering FePO4 from wastewater for Li-battery application.

Anti-Biofilm Enzymes-Assisted Antibiotic Therapy against Burn Wound Infection by Pseudomonas aeruginosa.

Pseudomonas aeruginosa can form biofilms at the site of burn wound, leading to infection and the failure of treatment regimens. The previous in vitro study demonstrated that a combination of the quorum-quenching enzyme AidHA147G and the extracellular matrix hydrolase PslG was effective in inhibiting biofilm and promoting antibiotic synergy. The aim of the present study was to evaluate the efficacy of this combination of enzymes in conjunction with tobramycin in treating burn wound infected with P. aeruginosa. The results showed that this treatment was effective in quorum-quenching and biofilm inhibition on infected wounds. Compared with the tobramycin treatment only, simultaneous treatment with the enzymes and antibiotics significantly reduced the severity of tissue damage, decreased the bacterial load, and reduced the expression of the inflammatory indicators myeloperoxidase (MPO) and malondialdehyde (MDA). Topical application of the enzymes also reduced the bacterial load and inflammation to some extent. These results indicate that the combined-enzyme approach is a potentially effective treatment for P. aeruginosa biofilm infections of burn wounds.

Piperlongumine overcomes imatinib resistance by inducing proteasome inhibition in chronic myelogenous leukemia cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Piper longum L., an herbal medicine used in India and other Asian countries, is prescribed routinely for a range of diseases, including tumor. Piperlongumine, a natural product isolated from Piper longum L., has received widespread attention due to its various pharmacological activities, such as anti-inflammatory, antimicrobial, and antitumor effects. AIM OF THE STUDY: Chronic myelogenous leukemia (CML) is a hematopoietic disease caused by Bcr-Abl fusion gene, with an incidence of 15% in adult leukemias. Targeting Bcr-Abl by imatinib provides a successful treatment approach for CML. However, imatinib resistance is an inevitable issue for CML treatment. In particular, T315I mutant is the most stubborn of the Bcr-Abl point mutants associated with imatinib resistance. Therefore, it is urgent to find an alternative approach to conquer imatinib resistance. This study investigated the role of a natural product piperlongumine in overcoming imatinib resistance in CML. MATERIALS AND METHODS: Cell viability and apoptosis were evaluated by MTS assay and Annexin V/propidium iodide counterstaining assay, respectively. Levels of intracellular signaling proteins were assessed by Western blots. Mitochondrial membrane potential was reflected by the fluorescence intensity of rhodamine-123. The function of proteasome was detected using 20S proteasomal activity assay, proteasomal deubiquitinase activity assay, and deubiquitinase active-site-directed labeling. The antitumor effects of piperlongumine were assessed with mice xenografts. RESULTS: We demonstrate that (i) Piperlongumine inhibits proteasome function by targeting 20S proteasomal peptidases and 19S proteasomal deubiquitinases (USP14 and UCHL5) in Bcr-Abl-WT and Bcr-Abl-T315I CML cells; (ii) Piperlongumine inhibits the cell viability of CML cell lines and primary CML cells; (iii) Proteasome inhibition by piperlongumine leads to cell apoptosis and downregulation of Bcr-Abl; (iv) Piperlongumine suppresses the tumor growth of CML xenografts. CONCLUSIONS: These results support that blockade of proteasome activity by piperlongumine provides a new therapeutic strategy for treating imatinib-resistant CML.

Occurrence and risk assessment of typical PPCPs and biodegradation pathway of ribavirin in wastewater treatment plants.

A large number of pharmaceuticals and personal care products (PPCPs) persist in wastewater, and the consumption of PPCPs for COVID-19 control and prevention has sharply increased during the pandemic. This study investigated the occurrence, removal efficiency, and risk assessment of six typical PPCPs commonly used in China in two wastewater treatment plants (WWTPs). Ribavirin (RBV) is an effective pharmaceutical for severely ill patients with COVID-19, and the possible biodegradation pathway of RBV by activated sludge was discovered. The experimental results showed that PPCPs were detected in two WWTPs with a detection rate of 100% and concentrations ranging between 612 and 2323 ng L-1. The detection frequency and concentrations of RBV were substantially higher, with a maximum concentration of 314 ng L-1. Relatively high pollution loads were found for the following PPCPs from influent: ibuprofen > ranitidine hydrochloride > RBV > ampicillin sodium > clozapine > sulfamethoxazole. The removal efficiency of PPCPs was closely related to adsorption and biodegradation in activated sludge, and the moving bed biofilm reactor (MBBR) had a higher removal capacity than the anoxic-anaerobic-anoxic-oxic (AAAO) process. The removal efficiencies of sulfamethoxazole, ampicillin sodium, ibuprofen, and clozapine ranged from 92.21% to 97.86% in MBBR process and were relatively low, from 61.82% to 97.62% in AAAO process, and the removal of RBV and ranitidine hydrochloride were lower than 42.96% in both MBBR and AAAO processes. The discrepancy in removal efficiency is caused by temperature, hydrophilicity, and hydrophobicity of the compound, and acidity and alkalinity. The transformation products of RBV in activated sludge were detected and identified, and the biodegradation process of RBV could be speculated as follows: first breaks into TCONH2 and an oxygen-containing five-membered heterocyclic ring under the nucleosidase reaction, and then TCONH2 is finally formed into TCOOH through amide hydrolysis. Aquatic ecological risks based on risk quotient (RQ) assessment showed that PPCPs had high and medium risks in the influent, and the RQ values were all reduced after MBBR and AAAO treatment. Ranitidine hydrochloride and clozapine still showed high and medium risks in the effluent, respectively, and thus presented potential risks to the aquatic ecosystem.

Inhibition of proteasomal deubiquitinases USP14 and UCHL5 overcomes tyrosine kinase inhibitor resistance in chronic myeloid leukaemia.

BACKGROUND: Chronic myeloid leukaemia (CML) is a haematological cancer featured by the presence of BCR-ABL fusion protein with abnormal tyrosine kinase activation. Classical tyrosine kinase inhibitor (TKI)-based therapies are available to patients with CML. However, acquired resistance to TKI has been a challenging obstacle, especially stubborn T315I mutation is the most common cause. Therefore, it is especially urgent to find more effective targets to overcome TKI resistance induced by BCR-ABLT315I . Proteasomal deubiquitinases (USP14 and UCHL5) have fundamental roles in the ubiquitin-proteasome system and possess multiple functions during cancer progression. METHODS: The human peripheral blood mononuclear cells were collected to measure the mRNA expression of USP14 and UCHL5, as well as to detect the toxicity effect of b-AP15. We explored the effect of b-AP15 on the activity of proteasomal deubiquitinases. We detected the effects of b-AP15 on BCR-ABLWT and BCR-ABLT315I CML cells in vitro and in the subcutaneous tumour model. We knocked down USP14 and/or UCHL5 by shRNA to explore whether these proteasomal deubiquitinases are required for cell proliferation of CML. RESULTS: In this study, we found that increased expression of the proteasomal deubiquitinase USP14 and UCHL5 in primary cancer cells from CML patients compared to healthy donors. b-AP15, an inhibitor of USP14 and UCHL5, exhibited potent tumour-killing activity in BCR-ABLWT and BCR-ABLT315I CML cell lines, as well as in CML xenografts and primary CML cells. Mechanically, pharmacological or genetic inhibition of USP14 and UCHL5 induced cell apoptosis and decreased the protein level of BCR-ABL in CML cells expressing BCR-ABLWT and BCR-ABLT315I . Moreover, b-AP15 synergistically enhanced the cytotoxic effect caused by TKI imatinib in BCR-ABLWT and BCR-ABLT315I CML cells. CONCLUSION: Collectively, our results demonstrate targeting USP14 and UCHL5 as a potential strategy for combating TKI resistance in CML.

Estrogen normalizes maternal HFD-induced vascular dysfunction in offspring by regulating ATR.

Previous studies have shown that female offspring are resistant to fetal high-fat diet (HFD)-induced programming of heightened vascular contraction; however, the underlying mechanisms remain unclear. The present study tested the hypothesis that estrogen plays a key role in protecting females from fetal programming of increased vascular contraction induced by maternal HFD exposure. Pregnant rats were fed a normal diet (ND) or HFD (60% kcal from fat). Ovariectomy (OVX) and 17ß-estradiol (E2) replacement were performed on 8-week-old female offspring. Aortas were isolated from adult female offspring. Maternal HFD exposure increased angiotensin II (Ang II)-induced contractions of the aorta in adult OVX offspring, which was abrogated by E2 replacement. The AT1 receptor (AT1R) antagonist losartan (10 µM), but not the AT2 receptor (AT2R) antagonist PD123319 (10 µM), completely blocked Ang II-induced contractions in both ND and HFD offspring. In addition, HFD exposure caused a decrease in endothelium-dependent relaxations induced by acetylcholine (ACh) in adult OVX but not OVX-E2 offspring. However, it had no effect on sodium nitroprusside (SNP)-induced endothelium-independent aorta relaxation in any of the six groups. Maternal HFD feeding increased AT1R, but not AT2R, leading to an increased AT1R/AT2R ratio in HFD-exposed OVX offspring, associated with selective decreases in DNA methylation at the AT1aR promoter, which was ameliorated by E2 replacement. Our results indicated that estrogen play a key role in sex differences of maternal HFD-induced vascular dysfunction and development of hypertensive phenotype in adulthood by differently regulating vascular AT1R and AT2R gene expression through a DNA methylation mechanism.

Cyclin-dependent kinase 7/9 inhibitor SNS-032 induces apoptosis in diffuse large B-cell lymphoma cells.

Approximately 40% of patients with diffuse large B-cell lymphoma (DLBCL) are refractory or relapse to standard chemotherapy, and most of them are activated B cell-like DLBCLs (ABC-DLBCL) and germinal center B cell-like DLBCLs (GCB-DLBCL). SNS-032, a novel and selective CDK7/9 inhibitor, that the first phase clinical trials approved by US FDA for cancer treatment have been completed. In this study, we investigated the anti-tumor effect of SNS-032 in ABC- and GCB-DLBCL subtypes. We report that SNS-032 induced growth inhibition and cell apoptosis in both DLBCL cells in vitro, and inhibited the growth of both DLBCL xenografts in nude mice. Mechanistically, SNS-032 inhibited RNA polymerase II, which led to transcriptional-dependent suppression of NF-κB signaling pathway and its downstream targets involved in cell survival; SNS-032 also downregulates BCL-2 and c-MYC in both mRNA and protein levels. Significantly, these findings provide pre-clinical evidence for application of targeting the CDK7/9 in DLBCL.

Superhydrophobic and deacidified cellulose/CaCO3-derived granular coating toward historic paper preservation.

Deacidification and surface self-cleaning are of great significance for the long-term preservation of historic literature. Herein, a superhydrophobic self-cleaning coating, derived from nanocellulose coated with CaCO3 particles is constructed via chemical vapor deposition (CVD) for the first time for the preservation of historic paper. The static contact angle of superhydrophobic paper reached more than 150° and the minimum sliding angle was 6.4°. Deacidification effect was achieved with a desired pH value in the range from 7.50 to 7.77 and the maximum alkali storage was up to 1.235 mol/kg. It is found that the low-cost CaCO3 nanoparticles can not only remove the acid substances, but also gave the paper function of self-cleaning, which is very great significant for the protection of paper-based relics.

Noninvasive prenatal testing of Duchenne muscular dystrophy in a twin gestation.

PURPOSE: Haplotype-based assay has been proved efficient in noninvasive prenatal testing for various monogenic disorders in singleton pregnancies. However, its application in twin pregnancies is still blank. Here we provide a novel algorithmic approach to noninvasively assess fetal genotypes in a dizygotic twin pregnancy at risk for Duchenne muscular dystrophy (DMD). METHODS: One pregnant woman carrying a dizygotic twin gestation was recruited as she was a heterozygote of DMD gene duplication and has delivered an affected son. Construction of parental haplotypes was achieved by target sequencing of DNA samples from the parent and the proband. Single nucleotide polymorphisms within target regions were classified into six categories according to parental haplotypes. Individual fetal fractions were calculated using paternal heterozygous. Maternal-inherited haplotype was deduced using relative haplotype dosage through a two-step Bayesian model. RESULTS: One male fetus with a lower fetal fraction of 4.6% and one female fetus with a higher fetal fraction of 10.1% were observed. The male fetus was predicted to be a DMD pathogenic variant carrier, while the female fetus was predicted to be homozygous normal. Noninvasive prenatal testing (NIPT) results were concordant with the findings of invasive prenatal diagnosis. CONCLUSIONS: This study is the first report of the use of NIPT for the assessment of DMD in a twin pregnancy. The algorithm provided could expand the use of NIPT to monogenic disorders in dizygotic twin pregnancies.

The effective removal of Congo Red using a bio-nanocluster: Fe3O4 nanoclusters modified bacteria.

A bio-nanocluster (Fe3O4@bacteria) was prepared by simply mixture using the bacterial suspension and Fe3O4 nanoclusters to remove Congo red (CR) contamination from water resources. The bio-nanocluster was characterized by SEM, TEM and XPS. Adsorption efficiency, adsorption process and adsorption mechanism were comprehensively investigated. The maximum adsorption capacity (Qm) of CR dye onto the Fe3O4@bacteria peaked at 320.1 mg/g, which was 2.88 times that of Fe3O4 under the same condition. Based on the equilibrium and kinetic studies, the Langmuir isotherm theory and pseudo-first-order model is appropriate to describe the adsorption process. The adsorption of CR is spontaneous and exothermic according to the thermodynamics parameters (ΔGθ, ΔHθ and ΔSθ). The adsorption force dominated the Van der Waals force, biofloculation and chemisorption. The Fe3O4@bacteria could be applied potentially as an absorbent with high efficiency and environmentally friendly remediation of dyeing wastewater.

Haplotype-Based Noninvasive Prenatal Diagnosis of 21 Families With Duchenne Muscular Dystrophy: Real-World Clinical Data in China.

Noninvasive prenatal diagnosis (NIPD) of single-gene disorders has recently become the focus of clinical laboratories. However, reports on the clinical application of NIPD of Duchenne muscular dystrophy (DMD) are limited. This study aimed to evaluate the detection performance of haplotype-based NIPD of DMD in a real clinical environment. Twenty-one DMD families at 7-12 weeks of gestation were prospectively recruited. DNA libraries of cell-free DNA from the pregnant and genomic DNA from family members were captured using a custom assay for the enrichment of DMD gene exons and spanning single-nucleotide polymorphisms, followed by next-generation sequencing. Parental haplotype phasing was based on family linkage analysis, and fetal genotyping was inferred using the Bayes factor through target maternal plasma sequencing. Finally, the entire experimental process was promoted in the local clinical laboratory. We recruited 13 complete families, 6 families without paternal samples, and 2 families without probands in which daughter samples were collected. Two different maternal haplotypes were constructed based on family members in all 21 pedigrees at as early as 7 gestational weeks. Among the included families, the fetal genotypes of 20 families were identified at the first blood collection, and a second blood collection was performed for another family due to low fetal concentration. The NIPD result of each family was reported within 1 week. The fetal fraction in maternal cfDNA ranged from 1.87 to 11.68%. In addition, recombination events were assessed in two fetuses. All NIPD results were concordant with the findings of invasive prenatal diagnosis (chorionic villus sampling or amniocentesis). Exon capture and haplotype-based NIPD of DMD are regularly used for DMD genetic diagnosis, carrier screening, and noninvasive prenatal diagnosis in the clinic. Our method, haplotype-based early screening for DMD fetal genotyping via cfDNA sequencing, has high feasibility and accuracy, a short turnaround time, and is inexpensive in a real clinical environment.

Deconstruction of biomass into lignin oil and platform chemicals over heteropoly acids with carbon-supported palladium as a hybrid catalyst under mild conditions.

In this work, near-complete conversion of lignocellulosic biomass and high products yields were achieved through catalytic transfer hydrogenolysis (CTH) in isopropanol using a heteropoly acid SiW12 synergistic with Pd/C catalyst at a relatively mild condition. The performances of various heteropoly acids and catalytic conditions were extensively examined. The results confirmed that SiW12 exhibited the highest activity on disrupting C-C linkages and C-O linkages than H2WO4, PW12, and PMo12. 34.91 wt% and 43.55 wt% monophenols were achieved for hydrogenolysis of bagasse and eucalyptus, respectively, at their optimal temperature for 5 h. Characterization studies on the lignin oil revealed that the notable structural changes were observed including the breaking of the side chain alkyl-aryl ether bonds and glycosidic bonds, while methoxyl groups were retained. Additionally, particle size of feedstock also has significant impact on the distribution and yields of the monophenols.

Synergy coordination of cellulose-based dialdehyde and carboxyl with Fe3+ recoverable conductive self-healing hydrogel for sensor.

A novel dual ionic network cellulose-based composite conductive self-healing hydrogel was fabricated with high elongation, rapid recoverability, high conductive sensitivity, self-healing ability and good biocompatibility. The hydrogel was constructed by the synergistic complexations of new-fashioned bidentate aldehyde groups on dialdehyde cellulose nanofibers (DACNFs) and carboxyl groups of acrylic acid (AA) with Fe3+. The elongation (~1300%) of the hydrogel containing 1 wt% DACNFs was approximate 13-fold of the pure PAA hydrogel and can recover to original state within 2 min after 80% compression. The self-healing efficiency increased with the addition of DACNFs in the dual ionic network cellulose-based composite conductive self-healing hydrogel. The hydrogel configured for a wearable test and showed high stretching sensitivity with a gauge factor of 13.82 at strain within 1.6%. The gauge factor (GF) decrease with the incremental strain within 20%. GF were 0.696 between 20% and 300% strain, 0.837 within 300% and 500%. Meanwhile, the current had a good linear relationship with the bending angles of hydrogels and pressure on hydrogels, which may provide a great potential in monitor both minor variations and large movements.

Estrogen normalizes maternal HFD-induced cardiac hypertrophy in offspring by regulating AT2R.

Our previous study has demonstrated maternal high-fat diet (HFD) caused sex-dependent cardiac hypertrophy in adult male, but not female offspring. The present study tested the hypothesis that estrogen normalizes maternal HFD-induced cardiac hypertrophy by regulating angiotensin II receptor (ATR) expression in adult female offspring. Pregnant rats were divided into the normal diet (ND) and HFD (60% kcal fat) groups. Ovariectomy (OVX) and 17ß-estradiol (E2) replacement were performed on 8-week-old female offspring. Maternal HFD had no effect on left ventricular (LV) wall thickness, cardiac function and molecular markers of cardiac hypertrophy function in sham groups. However, maternal HFD caused cardiac hypertrophy of offspring in OVX groups, which was abrogated by E2 replacement. In addition, maternal HFD had no effect on ERα and ERß in sham groups. In contrast, HFD significantly decreased ERα, but not ERß in OVX groups. In sham groups, there was no difference in the cardiac ATR type 1 (AT1R) and ATR type 2 (AT2R) between ND and HFD offspring. HFD significantly increased AT2R, but not AT1R in OVX groups. Furthermore, maternal HFD resulted in decreased glucocorticoid receptors (GRs) binding to the glucocorticoid response elements at the AT2R promoter, which was due to decreased GRs in hearts from OVX offspring. These HFD-induced changes in OVX groups were abrogated by E2 replacement. These results support a key role of estrogen in the sex difference of maternal HFD-induced cardiac hypertrophy in offspring, and suggest that estrogen protects female offspring from cardiac hypertrophy in adulthood by regulating AT2R.

Advances in Versatile Nanoscale Catalyst for the Reductive Catalytic Fractionation of Lignin.

In the past five years, biomass-derived biofuels and biochemicals were widely studied both in academia and industry as promising alternatives to petroleum. In this Review, the latest progress of the synthesis and fabrication of porous nanocatalysts that are used in catalytic transformations involving hydrogenolysis of lignin is reviewed in terms of their textural properties, catalytic activities, and stabilities. A particular emphasis is made with regard to the catalyst design for the hydrogenolysis of lignin and/or lignin model compounds. Furthermore, the effects of different supports on the lignin hydrogenolysis/hydrogenation are discussed in detail. Finally, the challenges and future opportunities of lignin hydrogenolysis over nanomaterial-supported catalysts are also presented.

Maternal high-fat diet increases vascular contractility in adult offspring in a sex-dependent manner.

A maternal high-fat diet (HFD) is a risk factor for cardiovascular diseases in offspring. The aim of the study was to determine whether maternal HFD causes the epigenetic programming of vascular angiotensin II receptors (ATRs) and leads to heightened vascular contraction in adult male offspring in a sex-dependent manner. Pregnant rats were treated with HFD (60% kcal fat). Aortas were isolated from adult male and female offspring. Maternal HFD increased phenylephrine (PE)-and angiotensin II (Ang II)-induced contractions of the aorta in male but not female offspring. NG-nitro-L-arginine (ʟ-NNA; 100 µM) abrogated the maternal HFD-induced increase in PE-mediated contraction. HFD caused a decrease in endothelium-dependent relaxations induced by acetylcholine in male but not female offspring. However, it had no effect on sodium nitroprusside-induced endothelium-independent relaxations of aortas regardless of sex. The AT1 receptor (AT1R) antagonist losartan (10 µM), but not the AT2 receptor (AT2R) antagonist PD123319 (10 µM), blocked Ang II-induced contractions in both control and HFD offspring in both sexes. Maternal HFD increased AT1R but decreased AT2R, leading to an increased ratio of AT1R/AT2R in HFD male offspring, which was associated with selective decreases in DNA methylation at the AT1aR promoter and increases in DNA methylation at the AT2R promoter. The vascular ratio of AT1R/AT2R was not significantly different in HFD female offspring compared with the control group. Our results indicated that maternal HFD caused a differential regulation of vascular AT1R and AT2R gene expression through a DNA methylation mechanism, which may be involved in HFD-induced vascular dysfunction and the development of a hypertensive phenotype in adulthood in a sex-dependent manner.

Selective hydrodeoxygenation of lignin model compound (3,4-dimethoxybenzyl alcohol) by Pd/CNX catalyst.

Upgrading of lignin derived bio-oil is an essential step for producing sustainable bio-based chemicals and fuel. Taken into account that α hydroxyl is the abundant functional group in lignin, high effective and selective catalytic alcoholysis for cleaving the Cα-OH linkages would be desirable. However, an in-depth understanding of the reaction mechanisms involved in the cleavage of Caromatic-Cα and Cα-O bonds over a novel catalyst is still needed. Herein, we report an efficient liquid-phase hydrogen transfer strategy for the selective hydrodeoxygenation of a non-phenolic lignin model compound, 3,4-dimethoxybenzyl (veratryl) alcohol, under mild conditions. By employing iso-propanol as solvent and H-donor, and palladium nanoparticles immobilized on nitrogen-doped carbon (Pd/CNX) as efficient multifunctional catalyst, veratryl alcohol dehydroxylation exhibited almost 100% conversion along with very high selectivity for 1,2-dimethoxy-benzene (46%) and 3,4-dimethoxytoluene (54%). Compared with other Pd catalysis, the Pd/CNX has excellent catalytic performances and exhibits higher selectivity for 3,4-dimethoxytoluene under incorporation with 1% HCOOH at 220 °C. The proportion of Pd (0) significantly increases in Pd/CNX catalyst when introduced into N precursor because of its highly dispersed Pd NPs and preventing the reoxidation of Pd (0). The dehydrogenation reaction occurred through the hydrogen generation of a secondary alcohol. Then, the Cα-OH and Caromatic-Cα bonds of veratryl alcohol were selectively cleaved by catalytic transfer hydrogenolysis. The alcoholysis mechanism is supported by dispersion-corrected density functional theory computations.