Lattice Strain Engineering on Metal-Organic Frameworks by Ligand Doping to Boost the Electrocatalytic Biomass Valorization.

As an efficient and environmental-friendly strategy, electrocatalytic oxidation can realize biomass lignin valorization by cleaving its aryl ether bonds to produce value-added chemicals. However, the complex and polymerized structure of lignin presents challenges in terms of reactant adsorption on the catalyst surface, which hinders further refinement. Herein, NiCo-based metal-organic frameworks (MOFs) are employed as the electrocatalyst to enhance the adsorption of reactant molecules through π-π interaction. More importantly, lattice strain is introduced into the MOFs via curved ligand doping, which enables tuning of the d-band center of metal active sites to align with the reaction intermediates, leading to stronger adsorption and higher electrocatalytic activity toward bond cleavage within lignin model compounds and native lignin. When 2'-phenoxyacetophenone is utilized as the model compound, high yields of phenol (76.3%) and acetophenone (21.7%) are achieved, and the conversion rate of the reactants reaches 97%. Following pre-oxidation of extracted poplar lignin, >10 kinds of phenolic compounds are received using the as-designed MOFs electrocatalyst, providing ≈12.48% of the monomer, including guaiacol, vanillin, eugenol, etc., and p-hydroxybenzoic acid dominates all the products. This work presents a promising and deliberately designed electrocatalyst for realizing lignin valorization, making significant strides for the sustainability of this biomass resource.

The FAcilitates Chromatin Transcription complex regulates the ratio of glycolysis to oxidative phosphorylation in neural stem cells.

Defects in the FAcilitates Chromatin Transcription (FACT) complex, a histone chaperone composed of SSRP1 and SUPT16H, are implicated in intellectual disability. Here, we reveal that the FACT complex promotes glycolysis and sustains the correct cell fate of neural stem cells/neuroblasts in the Drosophila 3rd instar larval central brain. We show that the FACT complex binds to the promoter region of the estrogen-related receptor (ERR) gene and positively regulates ERR expression. ERR is known to act as an aerobic glycolytic switch by upregulating the enzymes required for glycolysis. Dysfunction of the FACT complex leads to the downregulation of ERR transcription, resulting in a decreased ratio of glycolysis to oxidative phosphorylation (G/O) in neuroblasts. Consequently, neuroblasts exhibit smaller cell sizes, lower proliferation potential, and altered cell fates. Overexpression of ERR or suppression of mitochondrial oxidative phosphorylation in neuroblasts increases the relative G/O ratio and rescues defective phenotypes caused by dysfunction of the FACT complex. Thus, the G/O ratio, mediated by the FACT complex, plays a crucial role in neuroblast cell fate maintenance. Our study may shed light on the mechanism by which mutations in the FACT complex lead to intellectual disability in humans.

Hydrogen-transfer strategy in lignin refinery: Towards sustainable and versatile value-added biochemicals.

Lignin, the most prevalent natural source of polyphenols on Earth, offers substantial possibilities for the conversion into aromatic compounds, which is critical for attaining sustainability and carbon neutrality. The hydrogen-transfer method has garnered significant interest owing to its environmental compatibility and economic viability. The efficacy of this approach is contingent upon the careful selection of catalytic and hydrogen-donating systems that decisively affect the yield and selectivity of the monomeric products resulting from lignin degradation. This paper highlights the hydrogen-transfer technique in lignin refinery, with a specific focus on the influence of hydrogen donors on the depolymerization pathways of lignin. It delineates the correlation between the structure and activity of catalytic hydrogen-transfer arrangements and the gamut of lignin-derived biochemicals, utilizing data from lignin model compounds, separated lignin, and lignocellulosic biomass. Additionally, the paper delves into the advantages and future directions of employing the hydrogen-transfer approach for lignin conversion. In essence, this concept investigation illuminates the efficacy of the hydrogen-transfer paradigm in lignin valorization, offering key insights and strategic directives to maximize lignin's value sustainably.

Electrocatalytic Lignin Valorization into Aromatic Products via Oxidative Cleavage of Cα-Cß Bonds.

Lignin is the most promising candidate for producing aromatic compounds from biomass. However, the challenge lies in the cleavage of C-C bonds between lignin monomers under mild conditions, as these bonds have high dissociation energy. Electrochemical oxidation, which allows for mild cleavage of C-C bonds, is considered an attractive solution. To achieve low-energy consumption in the valorization of lignin, the use of highly efficient electrocatalysts is essential. In this study, a meticulously designed catalyst consisting of cobalt-doped nickel (oxy)hydroxide on molybdenum disulfide heterojunction was developed. The presence of molybdenum in a high valence state promoted the adsorption of tert-butyl hydroperoxide, leading to the formation of critical radical intermediates. In addition, the incorporation of cobalt doping regulated the electronic structure of nickel, resulting in a lower energy barrier. As a result, the heterojunction catalyst demonstrated a selectivity of 85.36% for cleaving the Cα-Cß bond in lignin model compound, achieving a substrate conversion of 93.69% under ambient conditions. In addition, the electrocatalyst depolymerized 49.82 wt% of soluble fractions from organosolv lignin (OL), resulting in a yield of up to 13 wt% of aromatic monomers. Significantly, the effectiveness of the prepared electrocatalyst was also demonstrated using industrial Kraft lignin (KL). Therefore, this research offers a practical approach for implementing electrocatalytic oxidation in lignin refining.

Hydrogen-Transfer Reductive Catalytic Fractionation of Lignocellulose: High Monomeric Yield with Switchable Selectivity.

Lignin solubilization and in situ hydrogenolysis are crucial for reductive catalytic fractionation (RCF) of lignocellulose to aromatic monomers. In this study, we reported a typical hydrogen bond acceptor of choline chloride (ChCl) to tailor the hydrogen-donating environment of the Ru/C-catalyzed hydrogen-transfer RCF of lignocellulose. The ChCl-tailored hydrogen-transfer RCF of lignocellulose was conducted under mild temperature and low-pressure (<1 bar) conditions, which was applicable to other lignocellulosic biomass sources. We obtained an approximate theoretical yield of propylphenol monomer of 59.2 wt % and selectivity of 97.3 % using an optimal content of ChCl (10 wt %) in ethylene glycol at 190 °C for 8 h. When the content of ChCl in ethylene glycol was increased to 110 wt %, the selectivity of propylphenol switched toward propylenephenol (yield of 36.2 wt % and selectivity of 87.6 %). The findings in this work provide valuable information for transforming lignin from lignocellulose into value-added products.

HR repair pathway plays a crucial role in maintaining neural stem cell fate under irradiation stress.

Environmental stress can cause mutation or genomic instability in stem cells which, in some cases, leads to tumorigenesis. Mechanisms to monitor and eliminate these mutant stem cells remain elusive. Here, using the Drosophila larval brain as a model, we show that X-ray irradiation (IR) at the early larval stage leads to accumulation of nuclear Prospero (Pros), resulting in premature differentiation of neural stem cells (neuroblasts, NBs). Through NB-specific RNAi screenings, we determined that it is the Mre11-Rad50-Nbs1 complex and the homologous recombination (HR) repair pathway, rather than non-homologous end-joining pathway that plays, a dominant role in the maintenance of NBs under IR stress. The DNA damage sensor ATR/mei-41 is shown to act to prevent IR-induced nuclear Pros in a WRNexo-dependent manner. The accumulation of nuclear Pros in NBs under IR stress, leads to NB cell fate termination, rather than resulting in mutant cell proliferation. Our study reveals an emerging mechanism for the HR repair pathway in maintaining neural stem cell fate under irradiation stress.

One-Pot Protolignin Extraction by Targeted Unlocking Lignin-Carbohydrate Esters via Nucleophilic Addition-Elimination Strategy.

Protolignin extraction can facilitate structure elucidation and valorization of lignin in biorefinery, but is rather challenging due to the complex chemical bonds present. Here, we developed the in situ generated NH3-reline (IGNR) system to realize one-pot protolignin extraction from lignocellulose. In the IGNR system, reline consisting of choline chloride and urea acted as both a solvent and a nucleophile generator, and the nucleophilic addition-elimination mechanism was verified by model compound studies. The in situ generated NH3 could precisely cleave the lignin-carbohydrate esters in lignocellulose with a near-quantitative retention of carbohydrates. The extracted IGNR-Protolignin exhibited native lignin substructure with high molecular weight and high ß-O-4' content (41.5 per 100 aromatic units). In addition, the up-scaled kilogram reaction demonstrated the feasibility of the IGNR system for potential industrial application in a green and sustainable pathway. This work represents a breakthrough toward protolignin extraction in practice with the future goal of achieving total biorefinery.

Co-dependent regulation of p-BRAF and potassium channel KCNMA1 levels drives glioma progression.

BRAF mutations have been found in gliomas which exhibit abnormal electrophysiological activities, implying their potential links with the ion channel functions. In this study, we identified the Drosophila potassium channel, Slowpoke (Slo), the ortholog of human KCNMA1, as a critical factor involved in dRafGOF glioma progression. Slo was upregulated in dRafGOF glioma. Knockdown of slo led to decreases in dRafGOF levels, glioma cell proliferation, and tumor-related phenotypes. Overexpression of slo in glial cells elevated dRaf expression and promoted cell proliferation. Similar mutual regulations of p-BRAF and KCNMA1 levels were then recapitulated in human glioma cells with the BRAF mutation. Elevated p-BRAF and KCNMA1 were also observed in HEK293T cells upon the treatment of 20 mM KCl, which causes membrane depolarization. Knockdown KCNMA1 in these cells led to a further decrease in cell viability. Based on these results, we conclude that the levels of p-BRAF and KCNMA1 are co-dependent and mutually regulated. We propose that, in depolarized glioma cells with BRAF mutations, high KCNMA1 levels act to repolarize membrane potential and facilitate cell growth. Our study provides a new strategy to antagonize the progression of gliomas as induced by BRAF mutations.

Brain-gut-liver axis: Chronic psychological stress promotes liver injury and fibrosis via gut in rats.

Background: The effect of chronic psychological stress on hepatitis and liver fibrosis is concerned. However, its mechanism remains unclear. We investigated the effect and mechanism of chronic psychological stress in promoting liver injury and fibrosis through gut. Methods: Sixty male SD rats were randomly assigned to 6 groups. Rat models of chronic psychological stress (4 weeks) and liver fibrosis (8 weeks) were established. The diversity of gut microbiota in intestinal feces, permeability of intestinal mucosa, pathologies of intestinal and liver tissues, collagen fibers, protein expressions of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor kappa ß (NF-κß), tumor necrosis factor α (TNF-α) and interleukin 1 (IL-1) in liver tissue, liver function and coagulation function in blood and lipopolysaccharide (LPS) in portal vein blood were detected and analyzed. Results: The diversities and abundances of gut microbiota were significant differences in rats among each group. The pathological lesions of intestinal and liver tissues, decreased expression of occludin protein in intestinal mucosa, deposition of collagen fibers and increased protein expression of TLR4, MyD88, NF-κß, TNF-α and IL-1 in liver tissue, increased LPS level in portal vein blood, and abnormalities of liver function and coagulation function, were observed in rats exposed to chronic psychological stress or liver fibrosis. There were significant differences with normal rats. When the dual intervention factors of chronic psychological stress and liver fibrosis were superimposed, the above indicators were further aggravated. Conclusion: Chronic psychological stress promotes liver injury and fibrosis, depending on changes in the diversity of gut microbiota and increased intestinal permeability caused by psychological stress, LPS that enters liver and acts on TLR4, and active LPS-TLR4 pathway depend on MyD88. It demonstrates the possibility of existence of brain-gut-liver axis.

Correlation analysis between physicians' evaluations of doctor-patient relationship and their preferences for shared decision-making in China.

Shared decision-making (SDM) is a scientific and reasonable decision-making model. However, whether physicians choose SDM is usually influenced by many factors. It is not clear whether the strained doctor-patient relationship will affect physicians' willingness to choose SDM. Through a survey by questionnaire, 304 physicians' evaluations of doctor-patient relationship (DPR) were quantified by the difficult DPR questionnaire-8. Their preferences for SDM and the reasons were also evaluated. The correlation between physicians' evaluations of DPR and their preferences for SDM were analyzed. 84.5% physicians perceived DPR as poor or strained, 53.3% physicians preferred SDM, mainly because of the influences of medical ethics and social desirability bias. Their preferences for SDM were not significantly correlated with their evaluations of DPR (P > 0.05). Physicians with different evaluations of DPR (good, poor, and strained) all had similar preferences for SDM (42.6, 56.4, and 42.9%), with no significant difference (P > 0.05). There was no correlation between physicians' evaluations of DPR and their preferences for SDM. Physicians' evaluations of poor DPR did not affect their preferences for SDM. This may be influenced by the medical ethics and social desirability bias.

Mxc, a Drosophila homolog of mental retardation-associated gene NPAT, maintains neural stem cell fate.

BACKGROUND: Mental retardation is a complex neurodevelopmental disorder. NPAT, a component of the histone locus body (HLB), has been implicated as a candidate gene for mental retardation, with a mechanism yet to be elucidated. RESULTS: We identified that mxc, the Drosophila ortholog of NPAT, is required for the development of nervous system. Knockdown of mxc resulted in a massive loss of neurons and locomotion dysfunction in adult flies. In the mxc mutant or RNAi knockdown larval brains, the neuroblast (NB, also known as neural stem cell) cell fate is prematurely terminated and its proliferation potential is impeded concurrent with the blocking of the differentiation process of ganglion mother cells (GMCs). A reduction of transcription levels of histone genes was shown in mxc knockdown larval brains, accompanied by DNA double-strand breaks (DSBs). The subsidence of histone transcription levels leads to prematurely termination of NB cell fate and blockage of the GMC differentiation process. Our data also show that the increase in autophagy induced by mxc knockdown in NBs could be a defense mechanism in response to abnormal HLB assembly and premature termination of NB cell fate. CONCLUSIONS: Our study demonstrate that Mxc plays a critical role in maintaining neural stem cell fate and GMC differentiation in the Drosophila larval brain. This discovery may shed light on the understanding of the pathogenesis of NPAT-related mental retardation in humans.

Transcriptome-Based Analysis Reveals Therapeutic Effects of Resveratrol on Endometriosis in aRat Model.

INTRODUCTION: Endometriosis (EMs) is associated with severe chronic pelvic pain and infertility and the development of improved EMs treatment options is an ongoing focus. In this study, we investigated the effects of resveratrol on EMs and analyzed transcriptional changes in the lesions of model rats before and after resveratrol treatment. METHODS: We established arat model of endometriosis through the trans-implantation of endometrial fragments to the peritoneal wall and then used resveratrol as treatment. We then analyzed the results using RNA sequencing of the lesion tissues of each of the model rats before resveratrol treatment and the reduced lesion tissues after the treatment. Examinations of anatomy, biochemistry, immunohistochemical staining and flow cytometry examinations were also conducted. Other trans-implanted rats were also given sham treatments as sham-treatment control and other untrans-implanted rats served as sham-operation controls. RESULTS: In addition to the obvious lesions observed in the model rats, there were significant differences in the glucose tolerance, macrophage M1/M2 polarization, and adipocyte sizes between the treated model rats and sham (control) rats. Resveratrol treatment in the model rats showed significant efficacy and positive therapeutic effect. Transcriptional analysis showed that the effects of resveratrol on the endometriosis model rats were manifested by alterations in the PPAR, insulin resistance, MAPK and PI3K/Akt signaling pathways. Correspondingly, changes in PPARγ activation, M1/M2 polarization and lipid metabolism were also detected after resveratrol treatment. DISCUSSION: Our study revealed that resveratrol treatment displayed efficient therapeutic effects for EMs model rats, probably through its important roles in anti-inflammation, immunoregulation and lipid-related metabolism regulation.