Responses of soil and rhizosphere microbial communities to Cd-hyperaccumulating willows and Cd contamination.

BACKGROUND: The pollution of soil by heavy metals, particularly Cd, is constitutes a critical international environmental concern. Willow species are renowned for their efficacy in the phytoremediation of heavy metals owing to their high Cd absorption rate and rapid growth. However, the mechanisms underlying microbial regulation for high- and low-accumulating willow species remain poorly understood. Therefore, we investigated the responses of soil and rhizosphere microbial communities to high- and low-Cd-accumulating willows and Cd contamination. We analyzed soil properties were analyzed in bulk soil (SM) and rhizosphere soil (RM) planted with high-accumulating (H) and low-accumulating (L) willow species. RESULTS: Rhizosphere soil for different willow species had more NH4+ than that of bulk soil, and RM-H soil had more than RM-L had. The available phosphorus content was greater in hyper-accumulated species than it was in lower-accumulated species, especially in RM-H. Genome sequencing of bacterial and fungal communities showed that RM-L exhibited the highest bacterial diversity, whereas RM-H displayed the greatest richness than the other groups. SM-L exhibited the highest diversity and richness of fungal communities. Ralstonia emerged as the predominant bacterium in RM-H, whereas Basidiomycota and Cercozoa were the most enriched fungi in SM-H. Annotation of the N and C metabolism pathways revealed differential patterns: expression levels of NRT2, NarB, nirA, nirD, nrfA, and nosZ were highest in RM-H, demonstrating the effects of NO3-and N on the high accumulation of Cd in RM-H. The annotated genes associated with C metabolism indicated a preference for the tricarboxylic pathway in RM-H, whereas the hydroxypropionate-hydroxybutyrate cycle was implicated in C sequestration in SM-L. CONCLUSIONS: These contribute to elucidation of the mechanism underlying high Cd accumulation in willows, particularly in respect of the roles of microbes and N and C utilization. This will provide valuable insights for repairing polluted soil using N and employing organic acids to improve heavy metal remediation efficiency.

Soliton-like surface plasmon polaritons generated on the surface of a silver nanowire embedded in a Kerr nonlinear medium.

The behavior of surface plasmon polaritons (SPPs) generated on the surface of a silver nanowire by coaxial Gaussian beams in Kerr nonlinear mediums is studied numerically. Enhancement of the propagation of the SPPs is realized due to the introduction of the nonlinear effect. Further adjusting the nonlinearity or the beam's intensity results in a soliton-like propagation of SPPs. This can be explained by the nonlinear self-focusing effect transferring more light into SPP modes and counteracting the attenuation caused by the absorption of metal. This result may contribute to SPP-based applications where an enhanced propagation length is needed.

Mechanochemical Approach for Air-Tolerant and Extremely Fast Lithium-Based Birch Reductions in Minutes.

Birch reduction has been widely used in organic synthesis for over half a century as a powerful method to dearomatize arenes into 1,4-cyclohexadiene derivatives. However, the conventional Birch reduction reaction using liquid ammonia requires laborious procedures to ensure inert conditions and low temperatures. Although several ammonia-free modifications have been reported, the development of an operationally simple, efficient, and scalable protocol remains a challenge. Herein, we report an ammonia-free lithium-based Birch reduction in air without special operating conditions using a ball-milling technique. This method is characterized by its operational simplicity and an extremely short reaction time (within 1 min), probably owing to the in situ mechanical activation of lithium metal, broad substrate scope, and no requirement for dry bulk solvents. The potential of our flash Birch reaction is also demonstrated by the efficient reduction of bioactive target molecules and gram-scale synthesis.

Palladium-Catalyzed Living/Controlled Vinyl Addition Polymerization of Cyclopropenes.

Despite the various utilities of cyclopropenes (CPEs) in organic synthesis and ring-opening metathesis polymerization (ROMP), their vinyl addition polymerization has been sporadically explored, and the corresponding living/controlled polymerization remains a formidable challenge. The major obstacle is the intrinsic instability of the intermediate and the kinetic barrier for propagation. Herein a living/controlled vinyl addition polymerization of 3-methyl-3-carboxymethyl CPEs, catalyzed by [Pd(π-allyl)Cl]2 ligated by a sulfinamide bisphosphine ligand, is demonstrated. A plot of the number-average molecular weight (Mn) versus the conversion was found to be linear during the polymerization, with the molecular weight dispersity (Mw/Mn) remaining narrow. The Mn values increased linearly with the increase in the initial feed ratio of monomer to catalyst. Furthermore, controlled block copolymerization via sequential monomer addition was successful. All of these points corroborate the living nature of this polymerization. The synergistic coordination action of the catalyst ligand and the lateral carbonyl group in the cyclopropene moiety plays a key role in achieving the efficient polymerization in a living/controlled manner.

In Situ Laser Scattering Electrospray Ionization Mass Spectrometry and Its Application in the Mechanism Study of Photoinduced Direct C-H Arylation of Heteroarenes.

An in situ laser scattering electrospray ionization mass spectrometry (LS-ESI-MS) was developed, where the laser scattering was simply achieved through the laser radiation of the "media" modified on the capillary. The laser scattering extended the reaction window and powerfully promoted the reaction yield of the photoinduced organic reaction, which enables the trace intermediates to be efficiently tracked in real time. For instance, the key radical cation in the photoinduced direct C-H arylation of heteroarenes was captured inventively, which provided direct experimental evidence for the verification of the reaction mechanism. Together with the characterization of oxidative photocatalytic Ru(III) intermediate, the integral insight into the process of visible-light-mediated direct C-H arylation of heteroarenes was confirmed. This approach is facile, powerful, and promising in the mechanism study of organic reaction.

Methylenetetrahydrofolate reductase polymorphisms and colorectal cancer prognosis: A meta-analysis.

BACKGROUND: The present study focused on understanding the prognostic value of the methylenetetrahydrofolate reductase (MTHFR) single nucleotide polymorphisms rs1801133 (C667T) and rs1801131 (A1298C) in patients with colorectal cancer (CRC). METHODS: A systematic literature search was conducted in March 2016. Databases, including Medline, EMBASE, Cochrane and Chinese databases (including CNKI, Wanfang and VIP), were searched to identify the relevant articles describing MTHFR polymorphisms in patients with CRC. Data regarding overall survival (OS), progression-free survival (PFS) and disease-free survival (DFS) were collected and analysed. RESULTS: Twenty-four studies with 5423 patients with CRC were included. Significant differences in OS, PFS and DFS were not observed among the different comparisons of patients carrying different alleles of the MTHFR rs1801133 polymorphism (including TT versus CC, TT versus CT + CC, CT + TT versus CC and CT versus CC). Compared with patients with the rs1801131 CA + AA genotypes, patients with the CC genotype had a shorter OS (hazard ratio = 1.85; 95% confidence interval = 1.30-2.65) and DFS (hazard ratio = 2.16; 95% confidence interval= 1.19-3.93). Significant differences in OS, PFS and DFS were not observed among the other patient groups (including CC versus AA, CC + CA versus AA and CA versus AA). Subgroup analysis of rs1801133 and rs1801131 showed that patients with CRC from Asian regions and Western regions demonstrated similar results. CONCLUSIONS: The MTHFR rs1801133 polymorphism was not associated with the prognosis of patients with CRC; however, rs1801131 may be associated with the prognosis of patients with CRC. Well-designed prospective studies are necessary to obtain a better understanding of the prognostic value of rs1801133 and rs1801131.

Cu(I)-Catalyzed Coupling of Bis(trimethylsilyl)diazomethane with Terminal Alkynes: A Synthesis of 1,1-Disilyl Allenes.

A Cu(I)-catalyzed cross-coupling reaction of terminal alkynes and bis(trimethylsilyl)diazomethane is reported. Mechanistically, the reaction is based on the recently developed cross-coupling reactions through metal-carbene migratory insertion. This reaction provides an efficient synthetic method for 1,1-disilyl allenes. Subsequent transformations of 1,1-disilyl allenes are investigated, which show diverse reactivities of these allenes.

Palladium-Catalyzed Oxygenative Cross-Coupling of Ynamides and Benzyl Bromides by Carbene Migratory Insertion.

A palladium-catalyzed oxygenative cross-coupling of ynamides and benzyl bromides has been developed. After subsequent hydrogenation, α,α-disubstituted amide derivatives were obtained in good yields. Migratory insertion of α-oxo palladium carbene species, generated by intermolecular oxidation, is proposed as the key step in this reaction. The study demonstrates the potential of ynamides to serve as carbene precursors in palladium-catalyzed C-C bond-forming cross-coupling reactions.

Facile synthesis of spirooxindole-pyrazolines and spirobenzofuranone-pyrazolines and their fungicidal activity.

Novel spirooxindole-pyrazolines and spirobenzofuranone-pyrazolines have been synthesized in good to excellent yields via the annulation reactions of the corresponding 3-alkylideneoxindoles and 3-alkylidenebenzofuranones with Huisgen zwitterions. The preliminary bioassay demonstrated that some of the spiropyrazolines possess good in vitro fungicidal activity against several crop fungi at a concentration of 50 µg mL(-1).

ChIPr: accurate prediction of cohesin-mediated 3D genome organization from 2D chromatin features.

The three-dimensional genome organization influences diverse nuclear processes. Here we present Chromatin Interaction Predictor (ChIPr), a suite of regression models based on deep neural networks, random forest, and gradient boosting to predict cohesin-mediated chromatin interaction strength between any two loci in the genome. The predictions of ChIPr correlate well with ChIA-PET data in four cell lines. The standard ChIPr model requires three experimental inputs: ChIP-Seq signals for RAD21, H3K27ac, and H3K27me3 but works well with just RAD21 signal. Integrative analysis reveals novel insights into the role of CTCF motif, its orientation, and CTCF binding on cohesin-mediated chromatin interactions.

Polymerizable rotaxane of cucurbituril protecting dopamine based adhesive hydrogels.

The catechol moiety found within mussel proteins plays a pivotal role in enhancing their adhesive properties. Nonetheless, catechol compounds, such as dopamine (DOP) derivatives, are susceptible to oxidation, leading to the formation of quinone. This oxidation process poses a significant challenge in the development of DOP-based hydrogels, hampering their adhesion capabilities and hindering polymerization. To protect DOP moieties from oxidation, DOP and N-(3-aminopropyl)methacrylamide (AMA) moieties were grafted onto the side groups of biocompatible poly(glutamic acid) (PGA). Subsequently, the DOP unit, serving as a second guest, would be captured by a polymerizable rotaxane of cucurbituril (CB[n]), in which the host molecule CB[8] complexed with the first guest, polymerizable methyl viologen (MV), forming a protective function and dynamic cross-linking. Upon exposure to light curing, a composite network emerged through the synergy of covalent cross-linking and supramolecular host-guest complexation of DOP with CB[8]. The generated complexation between DOP and CB[8] could protect the DOP moieties, resulting in photocured hydrogels with exceptional adhesive strength and remarkable tensile capabilities. Moreover, 3D printing technology was used to create various models with these DOP-based hydrogels, demonstrating their promising applications in future.

PRMT5 is an actionable therapeutic target in CDK4/6 inhibitor-resistant ER+/RB-deficient breast cancer.

CDK4/6 inhibitors (CDK4/6i) have improved survival of patients with estrogen receptor-positive (ER+) breast cancer. However, patients treated with CDK4/6i eventually develop drug resistance and progress. RB1 loss-of-function alterations confer resistance to CDK4/6i, but the optimal therapy for these patients is unclear. Through a genome-wide CRISPR screen, we identify protein arginine methyltransferase 5 (PRMT5) as a molecular vulnerability in ER+/RB1-knockout breast cancer cells. Inhibition of PRMT5 blocks the G1-to-S transition in the cell cycle independent of RB, leading to growth arrest in RB1-knockout cells. Proteomics analysis uncovers fused in sarcoma (FUS) as a downstream effector of PRMT5. Inhibition of PRMT5 results in dissociation of FUS from RNA polymerase II, leading to hyperphosphorylation of serine 2 in RNA polymerase II, intron retention, and subsequent downregulation of proteins involved in DNA synthesis. Furthermore, treatment with the PRMT5 inhibitor pemrametostat and a selective ER degrader fulvestrant synergistically inhibits growth of ER+/RB-deficient cell-derived and patient-derived xenografts. These findings highlight dual ER and PRMT5 blockade as a potential therapeutic strategy to overcome resistance to CDK4/6i in ER+/RB-deficient breast cancer.

IFN-γ inhibits liver progenitor cell proliferation in HBV-infected patients and in 3,5-diethoxycarbonyl-1,4-dihydrocollidine diet-fed mice.

BACKGROUND & AIMS: Proliferation of liver progenitor cells (LPCs) is associated with inflammation and fibrosis in chronic liver diseases. However, how inflammation and fibrosis affect LPCs remains obscure. METHODS: We examined the role of interferon (IFN)-γ, an important pro-inflammatory and anti-fibrotic cytokine, in LPC expansion in HBV-infected patients and in mice challenged with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)- or choline-deficient, ethionine-supplemented (CDE) diet as well as in primary LPCs and LPC cell line. RESULTS: The CK19 staining scores correlated with inflammation and fibrosis grades in the livers from 110 HBV-infected patients. Nine-month IFN-γ treatment decreased LPC numbers, inflammation, and fibrosis in these HBV-infected patients. Similarly, a two-week IFN-γ treatment also decreased LPC activation in DDC-treated mice. Disruption of IFN-γ or its signaling components (e.g., IFNGR, STAT1, and IRF-1) increased LPC proliferation and liver fibrosis in DDC-fed mice. In contrast, deletion of IFN-γ did not increase, but rather slightly reduced LPC proliferation in CDE-fed mice. In vitro, IFN-γ attenuated proliferation of the LPC cell line BMOL and of primary LPCs from wild type mice, but not STAT1(-/-) or IRF-1(-/-) mice. Furthermore, co-culture assays suggest that IFN-γ can indirectly promote LPC proliferation via the activation of macrophages but attenuate it via the inhibition of hepatic stellate cells. CONCLUSIONS: IFN-γ inhibits LPC expansion via the direct inhibition of LPC proliferation and indirect attenuation of liver fibrosis in the DDC model, but it may also enhance LPC expansion via the promotion of inflammation in the CDE model; thereby playing dual roles in regulating LPC proliferation in vivo.

Altered Fractional Amplitude of Low-Frequency Fluctuation in Anxious Parkinson's Disease.

OBJECTIVE: Anxiety symptoms are persistent in Parkinson's disease (PD), but the underlying neural substrates are still unclear. In the current study, we aimed to explore the underlying neural mechanisms in PD patients with anxiety symptoms. METHODS: 42 PD-A patients, 41 PD patients without anxiety symptoms (PD-NA), and 40 healthy controls (HCs) were recruited in the present study. All the subjects performed 3.0T fMRI scans. The fractional amplitude of low-frequency fluctuation (fALFF) analysis was used to investigate the alterations in neural activity among the three groups. A Pearson correlation analysis was performed between the altered fALFF value of the PD-A group and anxiety scores. RESULTS: Compared with HCs, PD-A patients had higher fALFF values in the left cerebellum, cerebellum posterior lobe, bilateral temporal cortex, and brainstem and lower fALFF values in the bilateral inferior gyrus, bilateral basal ganglia areas, and left inferior parietal lobule. Moreover, between the two PD groups, PD-A patients showed higher fALFF values in the right precuneus and lower fALFF values in the bilateral inferior gyrus, bilateral basal ganglia areas, left inferior parietal lobule, and left occipital lobe. Furthermore, Pearson's correlation analysis demonstrated that the right precuneus and left caudate were correlated with the Hamilton Anxiety Rating Scale scores. CONCLUSION: Our study found that anxiety symptoms in PD patients may be related to alterations of neurological activities in multiple brain regions. Furthermore, these may be critical radiological biomarkers for PD-A patients. Therefore, these findings can improve our understanding of the pathophysiological mechanisms underlying PD-A.

Research on Deterioration Mechanism and High-Precision Modelling of the Core Loss for Amorphous Alloys after Wire-Cut Electric Discharge Machining.

Amorphous alloys (AAs) have the advantage of low core loss. Thus, they can be used in high-speed motor applications. However, compared with the nominal performances, the performance of the wire-cut electric discharge machine (W-EDM)-processed AA iron core changes significantly, which limits its popularization. This paper focuses on the performance degradation mechanism of the AA ribbon caused by W-EDM and establishes a modified core loss model after machining. First, a 308 × 15 mm ribbon-shaped AA sample machined by W-EDM was prepared. The characterization and analysis of the magnetic properties, phase, magnetic domain, nano-indentation, micro-morphology, and composition were carried out. In this paper, by analysing the variation in the magnetic domain distribution based on domain width and nano-mechanical properties, it is proposed that the performance degradation range of AA ribbons processed by W-EDM is within 1 mm from the edge. By comparing the microscopic morphology and chemical composition changes in the affected and the unaffected area, this paper presents a mechanism for the property deterioration of W-EDM-processed AA ribbons based on electrochemical corrosion. Finally, a modified loss model for W-EDM-processed AAs is established based on the division of the affected area. This model can significantly improve the accuracy of core loss estimation in the medium- and high-frequency bands commonly used in high-speed motors.

Main-Chain Cationic Bile Acid Polymers Mimicking Facially Amphiphilic Antimicrobial Peptides.

Antibiotic-resistant bacterial infections have led to an increased demand for antibacterial agents that do not contribute to antimicrobial resistance. Antimicrobial peptides (AMPs) with the facially amphiphilic structures have demonstrated remarkable effectiveness, including the ability to suppress antibiotic resistance during bacterial treatment. Herein, inspired by the facially amphiphilic structure of AMPs, the facially amphiphilic skeletons of bile acids (BAs) are utilized as building blocks to create a main-chain cationic bile acid polymer (MCBAP) with macromolecular facial amphiphilicity via polycondensation and a subsequent quaternization. The optimal MCBAP displays an effective activity against Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative Escherichia coli, fast killing efficacy, superior bactericidal stability in vitro, and potent anti-infectious performance in vivo using the MRSA-infected wound model. MCBAP shows the low possibility to develop drug-resistant bacteria after repeated exposure, which may ascribe to the macromolecular facial amphiphilicity promoting bacterial membrane disruption and the generation of reactive oxygen species. The easy synthesis and low cost of MCBAP, the superior antimicrobial performance, and the therapeutic potential in treating MRSA infection altogether demonstrate that BAs are a promising group of building blocks to mimic the facially amphiphilic structure of AMPs in treating MRSA infection and alleviating antibiotic resistance.

NLRP12 downregulates the Wnt/ß-catenin pathway via interaction with STK38 to suppress colorectal cancer.

Colorectal cancer (CRC) at advanced stages is rarely curable, underscoring the importance of exploring the mechanism of CRC progression and invasion. NOD-like receptor family member NLRP12 was shown to suppress colorectal tumorigenesis, but the precise mechanism was unknown. Here, we demonstrate that invasive adenocarcinoma development in Nlrp12-deficient mice is associated with elevated expression of genes involved in proliferation, matrix degradation, and epithelial-mesenchymal transition. Signaling pathway analysis revealed higher activation of the Wnt/ß-catenin pathway, but not NF-κB and MAPK pathways, in the Nlrp12-deficient tumors. Using Nlrp12-conditional knockout mice, we revealed that NLRP12 downregulates ß-catenin activation in intestinal epithelial cells, thereby suppressing colorectal tumorigenesis. Consistent with this, Nlrp12-deficient intestinal organoids and CRC cells showed increased proliferation, accompanied by higher activation of ß-catenin in vitro. With proteomic studies, we identified STK38 as an interacting partner of NLRP12 involved in the inhibition of phosphorylation of GSK3ß, leading to the degradation of ß-catenin. Consistently, the expression of NLRP12 was significantly reduced, while p-GSK3ß and ß-catenin were upregulated in mouse and human colorectal tumor tissues. In summary, NLRP12 is a potent negative regulator of the Wnt/ß-catenin pathway, and the NLRP12/STK38/GSK3ß signaling axis could be a promising therapeutic target for CRC.

Critical role of antioxidant programs in enzalutamide-resistant prostate cancer.

Therapy resistance to second-generation androgen receptor (AR) antagonists, such as enzalutamide, is common in patients with advanced prostate cancer (PCa). To understand the metabolic alterations involved in enzalutamide resistance, we performed metabolomic, transcriptomic, and cistromic analyses of enzalutamide-sensitive and -resistant PCa cells, xenografts, patient-derived organoids, patient-derived explants, and tumors. We noted dramatically higher basal and inducible levels of reactive oxygen species (ROS) in enzalutamide-resistant PCa and castration-resistant PCa (CRPC), in comparison to enzalutamide-sensitive PCa cells or primary therapy-naive tumors respectively. Unbiased metabolomic evaluation identified that glutamine metabolism was consistently upregulated in enzalutamide-resistant PCa cells and CRPC tumors. Stable isotope tracing studies suggest that this enhanced glutamine metabolism drives an antioxidant program that allows these cells to tolerate higher basal levels of ROS. Inhibition of glutamine metabolism with either a small-molecule glutaminase inhibitor or genetic knockout of glutaminase enhanced ROS levels, and blocked the growth of enzalutamide-resistant PCa. The critical role of compensatory antioxidant pathways in maintaining enzalutamide-resistant PCa cells was validated by targeting another antioxidant program driver, ferredoxin 1. Taken together, our data identify a metabolic need to maintain antioxidant programs and a potentially targetable metabolic vulnerability in enzalutamide-resistant PCa.

Protein arginine methyltransferase 5 (PRMT5) is an actionable therapeutic target in CDK4/6 inhibitor-resistant ER+/RB-deficient breast cancer.

CDK4/6 inhibitors (CDK4/6i) have improved survival of patients with estrogen receptor-positive (ER+) breast cancer. However, patients treated with CDK4/6i eventually develop drug resistance and progress. RB1 loss-of-function alterations confer acquired resistance to CDK4/6i, but the optimal therapy for these patients is unclear. Using a genome-wide CRISPR screen, we identified protein arginine methyltransferase 5 (PRMT5) as a molecular vulnerability in ER+/RB1-knockout (RBKO) breast cancer cells. PRMT5 inhibition blocked cell cycle G1-to-S transition independent of RB, thus arresting growth of RBKO cells. Proteomics analysis uncovered fused in sarcoma (FUS) as a downstream effector of PRMT5. Pharmacological inhibition of PRMT5 resulted in dissociation of FUS from RNA polymerase II (Pol II), Ser2 Pol II hyperphosphorylation, and intron retention in genes that promote DNA synthesis. Treatment with the PRMT5i inhibitor pemrametostat and fulvestrant synergistically inhibited growth of ER+/RB-deficient patient-derived xenografts, suggesting dual ER and PRMT5 blockade as a novel therapeutic strategy to treat ER+/RB-deficient breast cancer.

Efficient access to materials-oriented aromatic alkynes via the mechanochemical Sonogashira coupling of solid aryl halides with large polycyclic conjugated systems.

Sonogashira coupling represents an indispensable tool for the preparation of organic materials that contain C(sp)-C(sp2) bonds. Improving the efficiency and generality of this methodology has long been an important research subject in materials science. Here, we show that a high-temperature ball-milling technique enables the highly efficient palladium-catalyzed Sonogashira coupling of solid aryl halides that bear large polyaromatic structures including sparingly soluble substrates and unactivated aryl chlorides. In fact, this new protocol provides various materials-oriented polyaromatic alkynes in excellent yield within short reaction times in the absence of bulk reaction solvents. Notably, we synthesized a new luminescent material via the mechanochemical Sonogashira coupling of poorly soluble Vat Red 1 in a much higher yield compared to those obtained using solution-based conditions. The utility of this method was further demonstrated by the rapid synthesis of a fluorescent metal-organic framework (MOF) precursor via two sequential mechanochemical Sonogashira cross-coupling reactions. The present study illustrates the great potential of Sonogashira coupling using ball milling for the preparation of materials-oriented alkynes and for the discovery of novel functional materials.