Hsa_circ_0006010 and hsa_circ_0002903 in peripheral blood serve as novel diagnostic, surveillance and prognostic biomarkers for disease progression in chronic myeloid leukemia.

BACKGROUND: In the era of tyrosine kinase inhibitor (TKI) treatment, the progression of chronic myeloid leukemia (CML) remains a significant clinical challenge, and genetic biomarkers for the early identification of CML patients at risk for progression are limited. This study explored whether essential circular RNAs (circRNAs) can be used as biomarkers for diagnosing and monitoring CML disease progression and assessing CML prognosis. METHODS: Peripheral blood (PB) samples were collected from 173 CML patients (138 patients with chronic phase CML [CML-CP] and 35 patients with accelerated phase/blast phase CML [CML-AP/BP]) and 63 healthy controls (HCs). High-throughput RNA sequencing (RNA-Seq) was used to screen dysregulated candidate circRNAs for a circRNA signature associated with CML disease progression. Quantitative real-time PCR (qRT-PCR) was used for preliminary verification and screening of candidate dysregulated genes, as well as subsequent exploration of clinical applications. Receiver operating characteristic (ROC) curve analysis, Spearman's rho correlation test, and the Kaplan-Meier method were used for statistical analysis. RESULTS: The aberrant expression of hsa_circ_0006010 and hsa_circ_0002903 during CML progression could serve as valuable biomarkers for differentiating CML-AP/BP patients from CMP-CP patients or HCs. In addition, the expression levels of hsa_circ_0006010 and hsa_circ_0002903 were significantly associated with the clinical features of CML patients but were not directly related to the four scoring systems. Furthermore, survival analysis revealed that high hsa_circ_0006010 expression and low hsa_circ_0002903 expression indicated poor progression-free survival (PFS) in CML patients. Finally, PB hsa_circ_0006010 and hsa_circ_0002903 expression at diagnosis may also serve as disease progression surveillance markers for CML patients but were not correlated with PB BCR-ABL1/ABL1IS. CONCLUSIONS: Our study demonstrated that PB levels of hsa_circ_0006010 and hsa_circ_0002903 may serve as novel diagnostic, surveillance, and prognostic biomarkers for CML disease progression and may contribute to assisting in the diagnosis of CML patients at risk for progression and accurate management of advanced CML patients.

Practical chemoselective aromatic substitution: the synthesis of N-(4-halo-2-nitrophenyl)benzenesulfonamide through the efficient nitration and halogenation of N-phenylbenzenesulfonamide.

A novel route involving the metal-promoted tandem nitration and halogenation of N-phenylbenzenesulfonamide to synthesize N-(4-halo-2-nitrophenyl)benzenesulfonamide derivatives has been developed. The method shows highly practical chemoselective and functional group compatibility. In addition, it employs insensitive and inexpensive Cu(NO3)2·3H2O, Fe(NO3)3·9H2O, and NH4NO3 as the nitration reagents, and it provides a direct approach for the preparation of 4-halo-2-nitroaniline, which is a crucial intermediate for the synthesis of benzimidazoles and quinoxaline derivatives.

Combination of PhI(OAc)2 and 2-Nitropropane as the Source of Methyl Radical in Room-Temperature Metal-Free Oxidative Decarboxylation/Cyclization: Construction of 6-Methyl Phenanthridines and 1-Methyl Isoquinolines.

A room-temperature metal-free method for generating highly unstable methyl radical was realized from the combination of PhI(OAc)2 and 2-nitropropane, which provides an efficient approach to methylated phenanthridines and isoquinolines. The strategy was also extended to the generation of other alkyl radicals and a concise synthesis of Roxadustat.

Closely related NAC transcription factors of tomato differentially regulate stomatal closure and reopening during pathogen attack.

To restrict pathogen entry, plants close stomata as an integral part of innate immunity. To counteract this defense, Pseudomonas syringae pv tomato produces coronatine (COR), which mimics jasmonic acid (JA), to reopen stomata for bacterial entry. It is believed that abscisic acid (ABA) plays a central role in regulating bacteria-triggered stomatal closure and that stomatal reopening requires the JA/COR pathway, but the downstream signaling events remain unclear. We studied the stomatal immunity of tomato (Solanum lycopersicum) and report here the distinct roles of two homologous NAC (for NAM, ATAF1,2, and CUC2) transcription factors, JA2 (for jasmonic acid2) and JA2L (for JA2-like), in regulating pathogen-triggered stomatal movement. ABA activates JA2 expression, and genetic manipulation of JA2 revealed its positive role in ABA-mediated stomatal closure. We show that JA2 exerts this effect by regulating the expression of an ABA biosynthetic gene. By contrast, JA and COR activate JA2L expression, and genetic manipulation of JA2L revealed its positive role in JA/COR-mediated stomatal reopening. We show that JA2L executes this effect by regulating the expression of genes involved in the metabolism of salicylic acid. Thus, these closely related NAC proteins differentially regulate pathogen-induced stomatal closure and reopening through distinct mechanisms.

Silver-catalyzed C2-selective direct alkylation of heteroarenes with tertiary cycloalkanols.

A silver-catalyzed regioselective C2-alkylation of heteroarenes with tertiary cycloalkanols under radical conditions was developed. This tandem process, which includes selective C-H activation, C(sp3)-C(sp3) bond cleavage, and C(sp3)-C(sp2) bond formation, affords a novel and environmentally friendly approach for the production of carbonyl-containing alkyl-substituted heteroarenes with moderate to good yields.

Selective remote esterification of 8-aminoquinoline amides via copper(ii)-catalyzed C(sp2)-O cross-coupling reaction.

The remote C-O coupling of quinoline amides at the C5 position has been established using cheap and readily available copper catalyst under mild conditions. The positionally selective esterification protocol afforded C-O coupling products in moderate to excellent yields. Most importantly, this method may provide a potential alternative to the existing ways to build functionalized 5-hydroxyquinoline derivatives, which are utilized as pivotal intermediates in the synthesis of drug candidates.

Copper/silver-mediated cascade reactions for the construction of 2-sulfonylbenzo[b]furans from trans-2-hydroxycinnamic acids and sodium sulfinates.

Efficient construction of 2-sulfonylbenzo[b]furans is achieved from readily available trans-2-hydroxycinnamic acids and sodium sulfinates mediated by the CuCl2·2H2O/AgTFA system under mild conditions. This unprecedented synthetic protocol provides expedient access to a series of products in one step via a protodecarboxylation/C-S bond formation/C-O bond formation cascade.

Inheritance of chlorantraniliprole resistance and fitness costs in a field population of Cnaphalocrocis medinalis (Lepidoptera: Pyralidae) in China.

BACKGROUND: Cnaphalocrocis medinalis is one of the major rice insect pests in Asia. Chlorantraniliprole is one of the most important insecticides for the control of C. medinalis. In this study, a field-resistant population and a susceptible strain of C. medinalis were used to evaluate the inheritance of chlorantraniliprole resistance and fitness costs in the field. RESULTS: The field-resistant population (Cm-RR) showed 128.4-fold resistance to chlorantraniliprole compared with the susceptible strain (Cm-SS). The dose-response of reciprocal cross progeny (F1 and F1') showed no significant difference, which indicated the inheritance of resistance to chlorantraniliprole in C. medinalis was autosomal. The degrees of dominance (D) of resistance for F1 and F1' were -0.19 and -0.05, respectively, indicating that the chlorantraniliprole resistance of C. medinalis was incompletely recessive inheritance. At the same time, significant differences between observed and expected mortalities of self-cross (F2 and F2') and backcross (BC and BC') progenies suggested chlorantraniliprole resistance is controlled by multiple genes. Furthermore, the Cm-RR population had a relative fitness of 0.32 with a substantially decreased pupation rate, emergence rate, fecundity, and substantially increased developmental time of larval and pupa stages. CONCLUSION: Current research showed that the inheritance of chlorantraniliprole resistance to C. medinalis was autosomal, incompletely recessive and multigene. The field-resistant population had a relative fitness of 0.32 when compared with the susceptible strain. This study provided valuable information for facilitating the development of chlorantraniliprole resistance management strategies. © 2024 Society of Chemical Industry.

Research trends and hot spots in global nanotechnology applications in liver cancer: a bibliometric and visual analysis (2000-2022).

Background: Liver cancer (LC) is one of the most common malignancies. Currently, nanotechnology has made great progress in LC research, and many studies on LC nanotechnology have been published. This study aims to discuss the current status, hot spots, and research trends in this field through bibliometric analysis. Methods: The Web of Science Core Collection (WoSCC) database was searched for papers related to hepatocellular carcinoma (HCC) included from January 2000 to November 2022, and its research hotspots and trends were visualized and analyzed with the help of VOSviewer. In addition, a search was conducted to find LC papers related to nanotechnology. Then we used the visual analysis software VOSviewer and CiteSpace to evaluate the contributions of countries/regions, authors, and journals related to the topic and analyze keywords to understand the research priorities and hot spots in the field as well as the development direction. Results: There are 1908 papers in the highly cited literature on LC, and its research hotspots are pathogenesis, risk factors, and survival rate. The literature on the application of nanotechnology in LC had 921 papers. Among them, China (n=560, 60.8%) and the United States (n=170, 18.5%) were the countries with the highest number of published papers. Wang Yan (n=11) and Llovet JM (n=131) were the first authors and co-cited authors, respectively. The International Journal of Nanomedicine was the most prolific academic journal (n=41). In addition to "hepatocellular carcinoma" and "nanoparticles", the most frequent keyword was "drug delivery". In recent years, "metastasis" and "diagnosis" appeared in the keyword bursts. This indicates that the application of nanoparticles in the early diagnosis and drug delivery of LC (including liver metastasis) has a good prospect. Conclusion: Nanotechnology has received more and more attention in the medical field in recent years. As nanoparticles are easily localized in organelles and cells, they can increase drug permeability in tumor tissues, improve drug delivery efficiency and reduce drug toxicity. Our research results were the first scientific evaluation of the application of nanotechnology in LC, providing scholars with research hotspots and development trends.

Experimental and Numerical Study on the Compressive Failure of Composite Laminates with Fiber Waviness Defects.

Fiber waviness defects are found in the inner surface of the hat-shaped stringers manufactured by a process system. In order to establish the acceptance criterion for the stringers with the fiber waviness defects, experimental testing and numerical simulation were carried out in this study. Specially induced fiber waviness defects of four pre-defined severity levels were manufactured and tested. A maximum of a 58.1% drop in compressive failure load is observed for the most severe level in the experimental results. A finite element model with progressive damage method and cohesive zone technique was developed to simulate the failure process and the impact of fiber waviness defects. The numerical simulation results of compressive failure load have a good agreement with experimental results qualitatively and quantitatively. In addition, two simple parameters, i.e., aspect ratio A/H and the number of plies with fiber waviness, are proposed to characterize the influence of the fiber waviness on the compressive failure load for the purpose of fast engineering quality checks.

A one-pot synthesis of AgBr/Ag3PO4 composite photocatalysts.

In this study, an AgBr/Ag3PO4 (ABAP) photocatalyst has been prepared via a facile one-pot anion-exchange method. SEM, XRD, XPS and UV-Vis DRS characterization techniques are carried out to study the structural and physicochemical characteristics of the AgBr/Ag3PO4 composites. The ABAP photocatalyst exhibited outstanding photocatalytic capability for the photodegradation of rhodamine B (RhB) under visible light irradiation. The optimal ABAP-48% composite displayed the highest photocatalytic activity; a complete degradation was attained in 25 min under visible light irradiation. The excellent stability and reusability of ABAP catalysts were examined by five subsequent runs. A probable degradation mechanism of ABAP composites was carefully surveyed. Furthermore, radical trapping experiments confirmed that the ˙O2 - radical was the main active species in the photodegradation reaction.

Rhodium-Catalyzed Regioselective Formal Hydroacylation of Vinyl Epoxides toward Esters Involving ß-Carbon Cleavage.

Herein we disclose the first example of the formal hydroacylation reactions of vinyl epoxides with chelating aldehydes enabled by rhodium catalysis for the efficient construction of functionalized esters. Detailed investigations of the mechanistic pathway reveal that the presence of a 2-vinyl group is essential in contributing to the success of this regioselective reaction, which might proceed through ß-carbon cleavage as the key procedure.

The synthesis of N,N'-disulfanediyl-bis(N'-((E)-benzylidene)acetohydrazide) from (E)-N'-benzylideneacetohydrazide and S8.

Herein we report an oxidative coupling reaction for N-S/S-S bond formation from (E)-N'-benzylideneacetohydrazide and S8 to furnish substituted N,N'-disulfanediyl-bis(N'-((E)-benzylidene) acetohydrazide). It provides a direct approach for the synthesis of disulfides with good yields.

Rhodium-Catalyzed Ring-Opening Hydroacylation of Alkylidenecyclopropanes with Chelating Aldehydes for the Synthesis of γ,δ-Unsaturated Ketones.

The first intermolecular ring-opening hydroacylation of alkylidenecyclopropanes with chelating aldehydes through a rhodium-catalyzed acrylamide-promoted protocol is reported. This highly efficient catalytic system enables the direct synthesis of a diverse range of linear γ,δ-unsaturated ketones. Good functional group compatibility is demonstrated for the completely atom-economical and remarkably selective proximal C-C bond cleavage process. Mechanistic studies reveal that the bidentate coordination of N,N-dimethylmethacrylamide (L1) to the acylrhodium intermediates might facilitate the cyclopropane ring fragmentation and isomerization.

Derivatives of Natural Product Agrimophol as Disruptors of Intrabacterial pH Homeostasis in Mycobacterium tuberculosis.

This article reports the rational medicinal chemistry of a natural product, agrimophol (1), as a new disruptor of intrabacterial pH (pHIB) homeostasis in Mycobacterium tuberculosis (Mtb). Through the systematic investigation of the structure-activity relationship of 1, scaffold-hopping of the diphenylmethane scaffold, pharmacophore displacement strategies, and studies of the structure-metabolism relationship, a new derivative 5a was achieved. Compound 5a showed 100-fold increased potency in the ability to reduce pHIB to pH 6.0 and similarly improved mycobactericidal activity compared with 1 against both Mycobacterium bovis-BCG and Mtb. Compound 5a possessed improved metabolic stability in human liver microsomes and hepatocytes, lower cytotoxicity, higher selectivity index, and similar pKa value to natural 1. This study introduces a novel scaffold to an old drug, resulting in improved mycobactericidal activity through decreasing pHIB, and may contribute to the critical search for new agents to overcome drug resistance and persistence in the treatment of tuberculosis.

Rhodium-Catalyzed Synthesis of α,ß-Unsaturated Ketones through Sequential C-C Coupling and Redox Isomerization.

A novel Rh(I)-catalyzed sequential C-C coupling and redox isomerization between allylic alcohols and 1,3-dienes has been accomplished. This versatile protocol provides expeditious access to a broad range of polysubstituted α,ß-unsaturated ketones with excellent atom economy and regioselectivity.

Functional Characterization of Two Elongases of Very Long-Chain Fatty Acid from Tenebrio molitor L. (Coleoptera: Tenebrionidae).

The elongases of very long chain fatty acid (ELOVL or ELO) are essential in the biosynthesis of fatty acids longer than C14. Here, two ELO full-length cDNAs (TmELO1, TmELO2) from the yellow mealworm (Tenebrio molitor L.) were isolated and the functions were characterized. The open reading frame (ORF) lengths of TmELO1 and TmELO2 were 1005 bp and 972 bp, respectively and the corresponding peptide sequences each contained several conserved motifs including the histidine-box motif HXXHH. Phylogenetic analysis demonstrated high similarity with the ELO of Tribolium castaneum and Drosophila melanogaster. Both TmELO genes were expressed at various levels in eggs, 1st and 2nd instar larvae, mature larvae, pupae, male and female adults. Injection of dsTmELO1 but not dsTmELO2 RNA into mature larvae significantly increased mortality although RNAi did not produce any obvious changes in the fatty acid composition in the survivors. Heterologous expression of TmELO genes in yeast revealed that TmELO1 and TmELO2 function to synthesize long chain and very long chain fatty acids.

Combined subacute toxicity of copper and antiparasitic albendazole to the earthworm (Eisenia fetida).

Copper (Cu) is one of the most common metal contaminants, and albendazole (ABZ) is a veterinary drug with a high efficacy against helminthes. It is believed that the two may co-exist in soil. In this study, the combined subacute toxicity of Cu exposure (0, 80, 120, 160 mg kg(-1)) and ABZ exposure (0, 3, 9 mg kg(-1)) in earthworms (Eisenia fetida) were observed using three approaches, namely chronic growth and reproduction, antioxidant enzyme activity, and earthworm Cu residue. The results have shown that the toxicity of Cu on cocoon hatching success and biomass was alleviated by presence of low concentrations of ABZ (3 mg kg(-1)) during a 56-day exposure period. However, the sensitivity of the earthworms' reproduction to Cu increased with the presence of high concentrations of ABZ (9 mg kg(-1)), indicating a reduction beginning at a Cu concentration of 80 mg kg(-1), in the cocoon number, hatching success, and biomass. In addition, the three enzyme activities exhibited different responsive patterns, indicating inducement in the catalase and glutathione peroxidase, and inhibition in the superoxide dismutase, which were dependent on the exposure times and concentrations. In regard to the earthworm Cu residue, when increasing Cu exposure concentrations, the internal Cu concentrations tended to level off, exhibited a linear pattern at the Cu concentration range of 40 to 120 mg kg(-1), and showed a stable trend above 120 mg kg(-1). The results of the present study can potentially provide important information regarding the combined toxicity of the veterinary drugs and the heavy metals in soil.

[Transformation of Populus tomentosa with anti-PLD gene].

Antisense Phospholipase Dgamma( PLDgamma) gene was introduced into Populus tomentosa mediated by Agrobactrium tumefaciens. The young leaves of triploid populus were used as the material and the regeneration system of high frequency has been established. We have developed the traditional transgene method by Agrobactrium trmefaciens and obtained many transgenic plants of anti-PLDgamma gene. Tests showed that the transgenic plants can grow well on the culture medium with 0.7% NaCl.