Aliphatic Hydrosilanes via Nickel-Catalyzed Reductive Csp3-Si Coupling of Primary Alkyl Bromides and Chlorohydrosilanes.

The reductive C-Si coupling of chlorosilanes offers efficient access to organosilanes, but its potential for constructing aliphatic ones remains largely unexplored. This manuscript presents a nickel-catalyzed Csp3-Si coupling reaction of unactivated alkyl-Br and R2Si(H)Cl. This work establishes a new approach for synthesizing highly functionalized aliphatic hydrosilanes from readily available chemical feedstocks. The reaction is easily scalable and can accommodate various functional groups, including carboxylic acids, which are usually incompatible with basic conditions.

Targeting Ferroptosis as an Advance Strategy in Cancer Therapy.

Ferroptosis, triggered by the buildup of lipid peroxidation and reliance on iron, is crucial in maintaining cellular balance. Research related to ferroptosis has surged due to its distinct characteristics compared to other forms of controlled cell death, both in terms of mechanisms and appearance. Scientists believe that directing efforts towards targeting ferroptosis could pave the way for innovative precision cancer treatments, addressing challenges such as cancer recurrence and resistance. This review systematically outlines the molecular mechanisms behind ferroptosis, the substances that induce ferroptosis, and how different cancers respond to ferroptotic inducers. Also, the study further looks into the molecular basis of ferroptosis in tumor biology. It provides a conceptual framework illustrating its interaction with the tumor immune microenvironment, guiding treatment choices, predicting efficacy, exploring combination therapies, and identifying new therapeutic targets to overcome cancer resistance to standard treatments. Finally, it highlights key issues and obstacles in future research and clinical translation of ferroptosis as a potential strategy in cancer therapy.

Association between pretreatment emotional distress and immune checkpoint inhibitor response in non-small-cell lung cancer.

Emotional distress (ED), commonly characterized by symptoms of depression and/or anxiety, is prevalent in patients with cancer. Preclinical studies suggest that ED can impair antitumor immune responses, but few clinical studies have explored its relationship with response to immune checkpoint inhibitors (ICIs). Here we report results from cohort 1 of the prospective observational STRESS-LUNG study, which investigated the association between ED and clinical efficacy of first-line treatment of ICIs in patients with advanced non-small-cell lung cancer. ED was assessed by Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7-item scale. The study included 227 patients with 111 (48.9%) exhibiting ED who presented depression (Patient Health Questionnaire-9 score ≥5) and/or anxiety (Generalized Anxiety Disorder 7-item score ≥5) symptoms at baseline. On the primary endpoint analysis, patients with baseline ED exhibited a significantly shorter median progression-free survival compared with those without ED (7.9 months versus 15.5 months, hazard ratio 1.73, 95% confidence interval 1.23 to 2.43, P = 0.002). On the secondary endpoint analysis, ED was associated with lower objective response rate (46.8% versus 62.1%, odds ratio 0.54, P = 0.022), reduced 2-year overall survival rate of 46.5% versus 64.9% (hazard ratio for death 1.82, 95% confidence interval 1.12 to 2.97, P = 0.016) and detriments in quality of life. The exploratory analysis indicated that the ED group showed elevated blood cortisol levels, which was associated with adverse survival outcomes. This study suggests that there is an association between ED and worse clinical outcomes in patients with advanced non-small-cell lung cancer treated with ICIs, highlighting the potential significance of addressing ED in cancer management. ClinicalTrials.gov registration: NCT05477979 .

Zirconium and hafnium catalyzed C-C single bond hydroboration.

Selective cleavage and subsequent functionalization of C-C single bonds present a fundamental challenge in synthetic organic chemistry. Traditionally, the activation of C-C single bonds has been achieved using stoichiometric transition-metal complexes. Recently, examples of catalytic processes were developed in which use is made of precious metals. However, the use of inexpensive and Earth-abundant group IV metals for catalytic C-C single-bond cleavage is largely underdeveloped. Herein, the zirconium-catalyzed C-C single-bond cleavage and subsequent hydroboration reactions is realized using Cp2ZrCl2 as a catalytic system. A series of structures of various γ-boronated amines are readily obtained, which are otherwise difficult to obtain. Mechanistic studies disclose the formation of a N-ZrIV species, and then a ß-carbon elimination route is responsible for C-C single bond activation. Besides zirconium, hafnium exhibits a similar performance for this transformation.

Bioinformatics Analysis and Experimental Validation of Differential Genes and Pathways in Bone Nonunions.

Non-union fractures pose a significant clinical challenge, often leading to prolonged pain and disability. Understanding the molecular mechanisms underlying non-union fractures is crucial for developing effective therapeutic interventions. This study integrates bioinformatics analysis and experimental validation to unravel key genes and pathways associated with non-union fractures. We identified differentially expressed genes (DEGs) between non-union and fracture healing tissues using bioinformatics techniques. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were employed to elucidate the biological processes and pathways involved. Common DEGs were identified, and a protein-protein interaction (PPI) network was constructed. Fibronectin-1 (FN1), Thrombospondin-1 (THBS1), and Biglycan (BGN) were pinpointed as critical target genes for non-union fracture treatment. Experimental validation involved alkaline phosphatase (ALP) and Alizarin Red staining to confirm osteogenic differentiation. Our analysis revealed significant alterations in pathways related to cell behavior, tissue regeneration, wound healing, infection, and immune responses in non-union fracture tissues. FN1, THBS1, and BGN were identified as key genes, with their upregulation indicating potential disruptions in the bone remodeling process. Experimental validation confirmed the induction of osteogenic differentiation. The study provides comprehensive insights into the molecular mechanisms of non-union fractures, emphasizing the pivotal roles of FN1, THBS1, and BGN in extracellular matrix dynamics and bone regeneration. The findings highlight potential therapeutic targets and pathways for further investigation. Future research should explore interactions between these genes, validate results using in vivo fracture models, and develop tailored treatment strategies for non-union fractures, promising significant advances in clinical management.

Targeting the Epigenetic Reader ENL Inhibits Super-Enhancer-Driven Oncogenic Transcription and Synergizes with BET Inhibition to Suppress Tumor Progression.

Epigenetic alterations at cis-regulatory elements (CRE) fine-tune transcriptional output. Epigenetic readers interact with CREs and can cooperate with other chromatin regulators to drive oncogene transcription. Here, we found that the YEATS domain-containing histone acetylation reader ENL (eleven-nineteen leukemia) acts as a key regulator of super-enhancers (SE), which are highly active distal CREs, across cancer types. ENL occupied the majority of SEs with substantially higher preference over typical enhancers, and the enrichment of ENL at SEs depended on its ability to bind acetylated histones. Rapid depletion of ENL by auxin-inducible degron tagging severely repressed the transcription of SE-controlled oncogenes, such as MYC, by inducing the decommissioning of their SEs, and restoring ENL protein expression largely reversed these effects. Additionally, ENL was indispensable for the rapid activation of SE-regulated immediate early genes in response to growth factor stimulation. Furthermore, ENL interacted with the histone chaperone FACT complex and was required for the deposition of FACT over CREs, which mediates nucleosome reorganization required for transcription initiation and elongation. Proper control of transcription by ENL and ENL-associated FACT was regulated by the histone reader BRD4. ENL was overexpressed in colorectal cancer and functionally contributed to colorectal cancer growth and metastasis. ENL degradation or inhibition synergized with BET inhibitors that target BRD4 in restraining colorectal cancer progression. These findings establish the essential role of epigenetic reader ENL in governing SE-driven oncogenic transcription and uncover the potential of ENL intervention to increase sensitivity to BET inhibition. SIGNIFICANCE: ENL plays a key role in decoding epigenetic marks at highly active oncogenic super-enhancers and can be targeted in combination with BET inhibition as a promising synergistic strategy for optimizing cancer treatment.

[Effects of Nitrogen Speciation Transformation on Microbial Community Succession in Input Rivers of Miyun Reservoir].

The Miyun Reservoir is the major source of surface drinking water in Beijing. However, the total nitrogen (TN) concentrations in the Miyun Reservoir and inflowing rivers have recently been increasing. In this study, the Mangniu River, a typical inflow river in the upper reaches of the Miyun Reservoir, was selected as the study area to investigate the spatial distribution and transformation of various nitrogen forms from the perspective of microbial community composition and predicting function, aimimg at providing a scientific reference for nitrogen pollution control of the Miyun Reservoir. The results indicated that except for TN, all the other physical and chemical water quality indicators in the upper reaches of the Miyun Reservoir met the Class II criteria of the environmental quality standards for surface water in China (GB 3838-2002). Additionally, NO3--N was the primary constituent of TN, ranging from 77.7% to 92.9%. Banchengzi Reservoir has a certain self-purification ability because its high C/N ratio promotes denitrification. Significant differences in microbial community structure were observed between the water and sediments of Mangniu River along with spatial distribution. High NO3--N concentration was the major environmental factor affecting the succession of microbial community structure. Many nitrification and denitrification microorganisms existed in Mengniu River, and the relative abundance of denitrification bacteria (DNB) was higher than that of nitrification bacteria, and that in the sediments was slightly higher than that in the water. Nitrosopumilus and Pseudomonas were the dominant nitrification and denitrification bacteria in Mengniuhe River, respectively. The results of phylogenetic investigation of communities by the reconstruction of unobserved states (PICRUSt2) showed that NO3--N reduction module was the major nitrogen metabolism module, which primarily occurred in water. The abundance of the functional genes for nitrification (i.e., narGH) was the highest in water, and the major functional gene involved in NO3--N reduction was nirBD of DNRA, which was primarily present in the sediments; however, the main functional gene involved in denitrification was nirK.

Oscillator Strengths and Cross Sections of the Valence-Shell Excitations of HBr Studied by Fast Electron Impact.

The oscillator strengths and cross sections of the valence-shell excitations of HBr were determined by fast electron scattering with an incident electron energy of 1500 eV and an energy resolution of 80 meV. The momentum transfer dependence behaviors of the generalized oscillator strengths have been used to elucidate the transition characteristics. The present results show that the strong spin-orbital interaction results in the observation of some triplet states in the (Λ, S) coupling and the constant generalized oscillator strength ratios for the pair states with the same electronic configuration and quantum number Ω, and the quantitative spin-orbit coupling coefficients of b3Π1(v = 0) and C1Π(v = 0) are determined. The optical oscillator strengths of the valence-shell excitations were obtained by extrapolating the generalized oscillator strengths to the limit of zero squared momentum transfer. The present optical oscillator strengths give an independent cross-check of the previous experimental and theoretical results, and the comparison shows that the line-saturation effect is more severe for the high Rydberg states with large intensities and narrow natural widths. The integral cross sections of the valence-shell excitations of HBr were obtained from the excitation threshold to 5000 eV by the BE-scaling method. The present oscillator strengths and cross sections supplement the fundamental molecular database of HBr and can be used for modeling in the semiconductor industry, astrophysics, and atmospheric chemistry.

Boosting activity of γ-alumina-supported vanadium catalyst for isobutane non-oxidative dehydrogenation via pure V3.

The vanadium-based dehydrogenation (DH) catalyst is becoming a promise alternative to the industrial used Pt- and Cr-based catalysts, due to lower cost and less environmental threat. However, the low DH activity hampered the industrial application of vanadium-based catalysts. Herein, for the first time, we introduce a method to prepare high-efficiency vanadium-based catalyst by constructing pure V3+ species on γ-Al2O3 through treatment of as-prepared thiovanadate. The V3+ species contributes to not only enhancing the DH activity, but also fabricating the V3+-O/S acid-base pair with ideal strength and stability. The isobutene yield can reach as high as 56.9 wt%. Only Lewis acid is recognized on V3+/Al2O3 catalyst, while no Brønsted acid remains. The side-reactions are consequently inhibited, and the selectivity to isobutene is improved. Besides, with the increase of vanadium loadings, the Lewis acid content increases at first and then decreases, and the content of acid sites in middle strength keeps decreasing. Though the deposited coke on V3+/Al2O3 was just 2.5 wt% during 8.5 h consecutive DH reaction, the valence state of vanadium was still influenced and the fraction of inert V4+ species increased steadily. This study will improve the potential for industrial application of vanadium-based DH catalyst, and offer theoretical guidance for optimization of ideal DH catalysts.

[Inhibitory Effect of Resveratrol on the Proliferation of Multiple Myeloma Cells and the Underlying Mechanism].

OBJECTIVE: To investigate the effect of resveratrol (RSV) on the proliferation of multiple myeloma (MM) cells and its molecular mechanism. METHODS: MM cells (MM1.S, RPMI-8226 and U266) were treated with different concentrations of RSV for 24-72 h. The effect of RSV on the proliferation of MM cells was detected by CCK-8 (cell counting kit-8) assay. RPMI-8226 cells were divided into RSV, miR-21 mimic, RSV+miR-21 mimic, miR-21 inhibitor and RSV+miR-21 inhibitor groups, and transfected with corresponding plasmids. The cell cycle distribution of each group was detected by flow cytometry with propidium iodide (PI) single staining. The cell apoptosis of each group was detected by AnnexinV-FITC/PE-PI double staining. The expression of miR-21 in MM cells treated with RSV and the expression of KLF5 mRNA in each group were detected by qRT-PCR. The expression of KLF5 protein in each group was detected by Western blot. RESULTS: RSV inhibited the proliferation and induced apoptosis of MM cells in a time- and dose-dependent manner. After the MM cells were treated with RSV, the number of cells in sub-G1 phase was increased, and that in G2/M phase was decreased. Moreover, RSV significantly downregulated the expression of miR-21 in MM cells, and the inhibitory effect of miR-21 mimic on KLF5 expression in MM cells was counteracted by RSV. CONCLUSION: RSV may inhibit the proliferation and induce apoptosis of MM cells by inhibiting miR-21 and up-regulating KLF5 expression.

Plasma metabolome identifies potential biomarkers of gastric precancerous lesions and gastric cancer risk.

OBJECTIVES: Currently, metabolic biomarkers with great practicability of gastric cancer (GC) and gastric precancerous lesions (GPL) are scarce. Thus, we are devoted to determining the plasma metabolic profiles of patients with GPL or GC and validate candidate biomarkers for disease diagnosis. METHODS: In this hospital-based case-control study, 68 plasma samples from 27 non-atrophic gastritis (NAG, control), 31 GPL, and 10 GC patients were collected for targeted metabolomics analysis. Univariate and multivariate analyses were used for selecting the differential metabolites. A receiver operating characteristic curve combined with binary logistic regression analysis was performed to test the diagnostic performance of the differential metabolites. Dietary data were obtained using a semiquantitative food frequency questionnaire. RESULTS: Distinct metabolomic profiles were noted for NAG, GPL, and GC. Compared to the NAG patients, the levels of 5 metabolites in the GPL group and 4 metabolites in the GC group were found to significantly elevate. Compared with the model involving 9 traditional risk factors (AUC: 0.89, 95%CI: 0.78-1.00), Trimethylamine N-oxide, the most significant metabolite (P = 2.00 × 10-5, FDR = 0.003, FC > 2, VIP > 2), showed a good diagnostic performance for the patients with GC (AUC: 0.90, 95%CI: 0.78-1.00), and its diagnostic performance has been further improved with the integration of Rhamnose (AUC: 0.96, 95%CI: 0.89-1.00). CONCLUSION: In our study, 9 defined metabolites might serve as meaningful biomarkers for identifying the high-risk population of GPL and GC, possibly enhancing the prevention and control of GPL and GC.

Estrogen-Induced LncRNA, LINC02568, Promotes Estrogen Receptor-Positive Breast Cancer Development and Drug Resistance Through Both In Trans and In Cis Mechanisms.

Endocrine therapy is the frontline treatment for estrogen receptor (ER) positive breast cancer patients. However, the primary and acquired resistance to endocrine therapy drugs remain as a major challenge in the clinic. Here, this work identifies an estrogen-induced lncRNA, LINC02568, which is highly expressed in ER-positive breast cancer and functional important in cell growth in vitro and tumorigenesis in vivo as well as endocrine therapy drug resistance. Mechanically, this work demonstrates that LINC02568 regulates estrogen/ERα-induced gene transcriptional activation in trans by stabilizing ESR1 mRNA through sponging miR-1233-5p in the cytoplasm. Meanwhile, LINC02568 contributes to tumor-specific pH homeostasis by regulating carbonic anhydrase CA12 in cis in the nucleus. The dual functions of LINC02568 together contribute to breast cancer cell growth and tumorigenesis as well as endocrine therapy drug resistance. Antisense oligonucleotides (ASO) targeting LINC02568 significantly inhibits ER-positive breast cancer cell growth in vitro and tumorigenesis in vivo. Furthermore, combination treatment with ASO targeting LINC02568 and endocrine therapy drugs or CA12 inhibitor U-104 exhibits synergistic effects on tumor growth. Taken together, the findings reveal the dual mechanisms of LINC02568 in regulating ERα signaling and pH homeostasis in ER-positive breast cancer, and indicated that targeting LINC02568 might represent a potential therapeutic avenue in the clinic.

Nickel-Catalyzed Reductive [4 + 1] Sila-Cycloaddition of 1,3-Dienes with Dichlorosilanes.

Transition-metal-catalyzed sila-cycloaddition has been a promising tool for accessing silacarbocycle derivatives, but the approach has been limited to a selection of well-defined sila-synthons. Herein, we demonstrate the potential of chlorosilanes, which are industrial feedstock chemicals, for this type of reaction under reductive nickel catalysis. This work extends the scope of reductive coupling from carbocycle to silacarbocycle synthesis and from single C-Si bond formation to sila-cycloaddition reactions. The reaction proceeds under mild conditions and shows good substrate scope and functionality tolerance, and it offers new access to silacyclopent-3-enes and spiro silacarbocycles. The optical properties of several spiro dithienosiloles as well as structural variations of the products are demonstrated.

Revision total hip arthroplasty using a fluted, tapered, modular stem follow-up method for a mean of three years: A preliminary study.

Objective: This study aimed to evaluate the results and complications related to revision total hip arthroplasty within a short-to-medium follow up period. Methods: From January 2016 to January 2020, we reviewed 31 prosthetic hip arthroplasty stem revisions using a fluted, tapered modular stem with distal fixation. The median age of the patients was 74.55-79 years. The survival rate was 100%, and there were no re-revisions. The Harris hip score improved from an average of 36.5 ± 7.8 before surgery to 81.8 ± 6.2 at the final follow-up. Results: The average final follow-up was 36 (24-60) months. During this time, there was no periprosthetic infection, no prosthesis loosening or breakage, and no sciatic nerve injury. Complications included four (12.9%) intraoperative fractures and eight (25.8%) dislocations that had no stem fractures. The postoperative limb was lengthened by 17.8 ± 9.8 mm. In most cases, bone regeneration was an early and important finding. Three cases underwent extended trochanteric osteotomy, and bone healing was achieved by the final follow-up. Conclusion: The modular tapered stem reviewed in this study was very versatile, could be used in most femoral revision cases, and allowed for rapid bone reconstruction. However, a long-term follow-up study is needed to confirm these results.

Targeting cancer metabolic vulnerabilities for advanced therapeutic efficacy.

Cancer metabolism is how cancer cells utilize nutrients and energy to support their growth and proliferation. Unlike normal cells, cancer cells have a unique metabolic profile that allows them to generate energy and the building blocks they need for rapid growth and division. This metabolic profile is marked by an increased reliance on glucose and glutamine as energy sources and changes in how cancer cells use and make key metabolic intermediates like ATP, NADH, and NADPH. This script analyzes a comprehensive overview of the latest advances in tumor metabolism, identifying the key unresolved issues, elaborates on how tumor cells differ from normal cells in their metabolism of nutrients, and explains how tumor cells conflate growth signals and nutrients to proliferate. The metabolic interaction of tumorigenesis and lipid metabolism within the tumor microenvironment and the role of ROS as an anti-tumor agent by mediating various signaling pathways for clinical cancer therapeutic targeting are outlined. Cancer metabolism is highly dynamic and heterogeneous; thus, advanced technologies to better investigate metabolism at the unicellular level without altering tumor tissue are necessary for better research and clinical transformation. The study of cancer metabolism is an area of active research, as scientists seek to understand the underlying metabolic changes that drive cancer growth and to identify potential therapeutic targets.

[Effects of whole grains on insulin resistance in overweight and obese adults: a Meta-analysis].

OBJECTIVE: To conduct a Meta-analysis of the effects of whole grains on insulin resistance in overweight and obese adults in randomize controlled trials. METHODS: Data were retrieved from PubMed, EMBASE, MEDLINE, Cochrane Library, CBM, CNKI and other databases from the database establishment to August 9, 2021. Randomize controlled trials of the effects of whole grains on insulin resistance in overweight and obese adults were screened out. Data extraction and quality evaluation were conducted for the literatures meeting the inclusion criteria. The Meta-analysis was conducted using R4.1.2 software. RESULTS: A total of 10 randomized controlled trials were included. Among the overweight and obese adults, the whole grains intake decreased their fasting plasma glucose(FPG)(MD=-0.08, 95%CI-0.12, -0.04), homeostasis model assessment of insulin resistance(HOMA-IR)(MD=-0.37, 95%CI-0.60, -0.14) and quantitative insulin sensitivity index(QUICKI)(MD=0.006, 95%CI 0.005, 0.007). However, there were no statistically significant among fasting insulin(FINS), postprandial blood glucose(PG), postprandial insulin(PI), and triglycerides(TG) in overweight and obese adults. In subgroup analysis, FPG was statistically significant in German, quality score 4, 150-200 g intake of whole grain, and health subgroups of each population. There was no statistical significance of the QUICKI group. In sensitivity analysis and publication bias, FINS, PG, PI and TG became significant after one article was removed. However, HOMA-IR result were not statistically significant after the removal of one article. Meanwhile, the publication bias of each index was analyzed by Egger regression. Based on the results of subgroup analysis, a further dose-response analysis was conducted on the whole grains intake. The result showed that the FPG effects scale was better when the daily intake of whole grains was between 140 g and 160 g. CONCLUSION: Daily intake of 140 g to 160 g of whole grains improves FPG levels in overweight and obese adults.

A novel tumor suppressor encoded by a 1p36.3 lncRNA functions as a phosphoinositide-binding protein repressing AKT phosphorylation/activation and promoting autophagy.

Peptides/small proteins, encoded by noncanonical open reading frames (ORF) of previously claimed non-coding RNAs, have recently been recognized possessing important biological functions, but largely uncharacterized. 1p36 is an important tumor suppressor gene (TSG) locus frequently deleted in multiple cancers, with critical TSGs like TP73, PRDM16, and CHD5 already validated. Our CpG methylome analysis identified a silenced 1p36.3 gene KIAA0495, previously thought coding long non-coding RNA. We found that the open reading frame 2 of KIAA0495 is actually protein-coding and translating, encoding a small protein SP0495. KIAA0495 transcript is broadly expressed in multiple normal tissues, but frequently silenced by promoter CpG methylation in multiple tumor cell lines and primary tumors including colorectal, esophageal and breast cancers. Its downregulation/methylation is associated with poor survival of cancer patients. SP0495 induces tumor cell apoptosis, cell cycle arrest, senescence and autophagy, and inhibits tumor cell growth in vitro and in vivo. Mechanistically, SP0495 binds to phosphoinositides (PtdIns(3)P, PtdIns(3,5)P2) as a lipid-binding protein, inhibits AKT phosphorylation and its downstream signaling, and further represses oncogenic AKT/mTOR, NF-κB, and Wnt/ß-catenin signaling. SP0495 also regulates the stability of autophagy regulators BECN1 and SQSTM1/p62 through modulating phosphoinositides turnover and autophagic/proteasomal degradation. Thus, we discovered and validated a 1p36.3 small protein SP0495, functioning as a novel tumor suppressor regulating AKT signaling activation and autophagy as a phosphoinositide-binding protein, being frequently inactivated by promoter methylation in multiple tumors as a potential biomarker.

A distal super-enhancer activates oncogenic ETS2 via recruiting MECOM in inflammatory bowel disease and colorectal cancer.

Abnormal activities of distal cis-regulatory elements (CREs) contribute to the initiation and progression of cancer. Gain of super-enhancer (SE), a highly active distal CRE, is essential for the activation of key oncogenes in various cancers. However, the mechanism of action for most tumor-specific SEs still largely remains elusive. Here, we report that a candidate oncogene ETS2 was activated by a distal SE in inflammatory bowel disease (IBD) and colorectal cancer (CRC). The SE physically interacted with the ETS2 promoter and was required for the transcription activation of ETS2. Strikingly, the ETS2-SE activity was dramatically upregulated in both IBD and CRC tissues when compared to normal colon controls and was strongly correlated with the level of ETS2 expression. The tumor-specific activation of ETS2-SE was further validated by increased enhancer RNA transcription from this region in CRC. Intriguingly, a known IBD-risk SNP resides in the ETS2-SE and the genetic variant modulated the level of ETS2 expression through affecting the binding of an oncogenic transcription factor MECOM. Silencing of MECOM induced significant downregulation of ETS2 in CRC cells, and the level of MECOM and ETS2 correlated well with each other in CRC and IBD samples. Functionally, MECOM and ETS2 were both required for maintaining the colony-formation and sphere-formation capacities of CRC cells and MECOM was crucial for promoting migration. Taken together, we uncovered a novel disease-specific SE that distantly drives oncogenic ETS2 expression in IBD and CRC and delineated a mechanistic link between non-coding genetic variation and epigenetic regulation of gene transcription.

Nickel-Catalyzed Reductive Coupling of Chlorosilanes.

Organosilanes play essential roles in many important research areas. The use of readily available chlorosilanes to catalytically access these compounds is synthetically appealing but remains a long-standing challenge. Nickel-catalyzed reductive cross-coupling reaction has recently emerged as a promising protocol to arrive at this goal. This strategy allows the chlorosilanes to be coupled with various carbon electrophiles under mild conditions. These reactions afford organosilanes with improved molecular diversity, structural complexity, and functional group compatibility. This Concept article summarizes the recent advance on nickel-catalyzed reductive C-Si couplings of chlorosilanes.