Iron-Catalyzed Aminoalkylative Carbonylative Cyclization of Alkenes toward α-Tetralones.

Carbonylative multifunctionalization of alkenes is an efficient approach to introduce multiple functional groups into one molecule from easily available materials. Herein, we developed an iron-catalyzed radical relay carbonylative cyclization of alkenes with acetamides. Various α-tetralones can be constructed in moderate yields from readily available substrates with an earth-abundant iron salt as the catalyst.

Bioinspired Bottlebrush Polymers Effectively Alleviate Frictional Damage Both In Vitro and In Vivo.

Bottlebrush polymers (BB) have emerged as compelling candidates for biosystems to face tribological challenges, including friction and wear. This study provides a comprehensive assessment of an engineered triblock BB polymer's affinity, cell toxicity, lubrication, and wear protection in both in vitro and in vivo settings, focusing on applications for conditions like osteoarthritis and dry eye syndrome. Results show that the designed polymer rapidly adheres to various surfaces (e.g., cartilage, eye, and contact lens), forming a robust, biocompatible layer for surface lubrication and protection. The tribological performance and biocompatibility are further enhanced in the presence of hyaluronic acid (HA) both in vitro and in vivo. The exceptional lubrication performance and favorable interaction with HA position the synthesized triblock polymer as a promising candidate for innovative treatments addressing deficiencies in bio-lubricant systems.

Direct C-H Sulfuration: Synthesis of Disulfides, Dithiocarbamates, Xanthates, Thiocarbamates and Thiocarbonates.

In light of the important biological activities and widespread applications of organic disulfides, dithiocarbamates, xanthates, thiocarbamates and thiocarbonates, the continual persuit of efficient methods for their synthesis remains crucial. Traditionally, the preparation of such compounds heavily relied on intricate multi-step syntheses and the use of highly prefunctionalized starting materials. Over the past two decades, the direct sulfuration of C-H bonds has evolved into a straightforward, atom- and step-economical method for the preparation of organosulfur compounds. This review aims to provide an up-to-date discussion on direct C-H disulfuration, dithiocarbamation, xanthylation, thiocarbamation and thiocarbonation, with a special focus on describing scopes and mechanistic aspects. Moreover, the synthetic limitations and applications of some of these methodologies, along with the key unsolved challenges to be addressed in the future are also discussed. The majority of examples covered in this review are accomplished via metal-free, photochemical or electrochemical approaches, which are in alignment with the overraching objectives of green and sustainable chemistry. This comprehensive review aims to consolidate recent advancements, providing valuable insights into the dynamic landscape of efficient and sustainable synthetic strategies for these crucial classes of organosulfur compounds.

Recent advances in selective mono-/dichalcogenation and exclusive dichalcogenation of C(sp2)-H and C(sp3)-H bonds.

Organochalcogen compounds are prevalent in numerous natural products, pharmaceuticals, agrochemicals, polymers, biological molecules and synthetic intermediates. Direct chalcogenation of C-H bonds has evolved as a step- and atom-economical method for the synthesis of chalcogen-bearing compounds. Nevertheless, direct C-H chalcogenation severely lags behind C-C, C-N and C-O bond formations. Moreover, compared with the C-H monochalcogenation, reports of selective mono-/dichalcogenation and exclusive dichalcogenation of C-H bonds are relatively scarce. The past decade has witnessed significant advancements in selective mono-/dichalcogenation and exclusive dichalcogenation of various C(sp2)-H and C(sp3)-H bonds via transition-metal-catalyzed/mediated, photocatalytic, electrochemical or metal-free approaches. In light of the significance of both mono- and dichalcogen-containing compounds in various fields of chemical science and the critical issue of chemoselectivity in organic synthesis, the present review systematically summarizes the advances in these research fields, with a special focus on elucidating scopes and mechanistic aspects. Moreover, the synthetic limitations, applications of some of these processes, the current challenges and our own perspectives on these highly active research fields are also discussed. Based on the substrate types and C-H bonds being chalcogenated, the present review is organized into four sections: (1) transition-metal-catalyzed/mediated chelation-assisted selective C-H mono-/dichalcogenation or exclusive dichalcogenation of (hetero)arenes; (2) directing group-free selective C-H mono-/dichalcogenation or exclusive dichalcogenation of electron-rich (hetero)arenes; (3) C(sp3)-H dichalcogenation; (4) dichalcogenation of both C(sp2)-H and C(sp3)-H bonds. We believe the present review will serve as an invaluable resource for future innovations and drug discovery.

From bonds to interactions: comprehensive molecular characterization via polarizable bond-dipole approach.

Accurately characterizing molecular interactions stands as a pivotal requirement for ensuring the reliability of molecular dynamics simulations. In line with our bond-dipole-based interaction model proposed by Gao et al. [X.-C. Gao, Q. Hao and C.-S. Wang, J. Chem. Theory Comput., 2017, 13, 2730-2741.], we have implemented an efficient and concise approach to compute electrostatic potential. This methodology capitalizes on the polarizable nature of chemical bond dipoles, resulting in a model of remarkable simplicity. In this study, we have revised the polarizable bond-dipole-based force field (PBFF) through the meticulous curation of quantum chemical data sets. These data sets encompass a comprehensive collection of 40 000 conformations, including those of water, methylamine, methanol, and N-methylacetamide. Additionally, we incorporate 520 hydrogen-bonded dimers into our data sets. In pursuit of enhanced accuracy in molecular dynamics simulations and a more faithful representation of potential energy landscapes, we undertook the re-optimization of the nonbonded parameters within the PBFF framework. Concurrently, we intricately fine-tuned the bonded parameters. The results of our comprehensive evaluation denote that this newly optimized force field method adeptly and efficiently computes structural characteristics, harmonic frequencies, and interaction energies. Overall, this study provides further validation for the applicability of PBFF in molecular dynamics simulations.

Cobalt-Catalyzed Carbonylative Synthesis of 4-Oxobutanoates from Formamide and Ethylene.

The direct concurrent installation of amide and ester groups across olefin motifs represents a powerful and promising functionalization tool in organic chemistry. Herein, a ligand-free cobalt-catalyzed four-component radical relay carbonylative difunctionalization of ethylene for the synthesis of 4-oxobutanoates has been developed. Valuable C4 building blocks were produced in a highly atom-economical fashion.

Rice GA3ox1 modulates pollen starch granule accumulation and pollen wall development.

The rice GA biosynthetic gene OsGA3ox1 has been proposed to regulate pollen development through the gametophytic manner, but cellular characterization of its mutant pollen is lacking. In this study, three heterozygotic biallelic variants, "-3/-19", "-3/-2" and "-3/-10", each containing one null and one 3bp-deletion allele, were obtained by the CRISPR/Cas9 technique for the functional study of OsGA3ox1. The three homozygotes, "-19/-19", "-2/-2" and "-10/-10", derived from heterozygotic variants, did not affect the development of most vegetative and floral organs but showed a significant reduction in seed-setting rate and in pollen viability. Anatomic characterizations of these mutated osga3ox1 pollens revealed defects in starch granule accumulation and pollen wall development. Additional molecular characterization suggests that abnormal pollen development in the osga3ox1 mutants might be linked to the regulation of transcription factors OsGAMYB, OsTDR and OsbHLH142 during late pollen development. In brief, the rice GA3ox1 is a crucial gene that modulates pollen starch granule accumulation and pollen wall development at the gametophytic phase.

Cobalt-Catalyzed Hydroxymethylation of Alkyl Halides with CO as the C1 Source.

Herein, we developed an effective strategy for the synthesis of one-carbon-extended alcohols through cobalt-catalyzed hydroxymethylation of alkyl halides with carbon monoxide as the C1 source and cheap and environmentally friendly PMHS as the hydride source. This procedure also features a ligand-free cobalt catalyst and a broad range of functional group tolerance.

Merging C-H Bond Activation, Alkyne Insertion, and Rearrangements by Rh(III)-Catalysis: Oxindole Synthesis from Nitroarenes and Alkynes.

We report a Rh(III)-catalyzed ortho-C-H bond functionalization of nitroarenes with 1,2-diarylalkynes and carboxylic anhydrides. The reaction unpredictably affords 3,3-disubstituted oxindoles with the formal reduction of the nitro group under redox-neutral conditions. Besides good functional group tolerance, this transformation allows the preparation of oxindoles with a quaternary carbon stereocenter using nonsymmetrical 1,2-diarylalkynes. This protocol is facilitated by the use of a functionalized cyclopentadienyl (CpTMP*)Rh(III) [CpTMP* = 1-(3,4,5-trimethoxyphenyl)-2,3,4,5-tetramethylcyclopentadienyl] catalyst we developed, which combines an electron-rich character with an elliptical shape. Mechanistic investigations, including the isolation of three rhodacyle intermediates and extensive density functional theory calculations, indicate that the reaction proceeds through nitrosoarene intermediates via a cascade of C-H bond activation─O-atom transfer─[1,2]-aryl shift─deoxygenation─N-acylation.

A scheme for rapid evaluation of the intermolecular three-body polarization effect in water clusters.

The ability to accurately and rapidly evaluate the intermolecular many-body polarization effect of the water system is very important for computer simulations of biomolecule in aqueous. In this paper, a scheme is proposed based on the polarizable dipole-dipole interaction model and used to rapidly estimate the intermolecular many-body polarization effect in water clusters. We use a bond-dipole-based polarization function to evaluate the polarization energy. We regard two OH bonds of a water molecule as two bond-dipoles and set the permanent OH bond-dipole moment of a water molecule to be 1.51 Debye. We estimate the induced OH bond-dipole moment via a simple formula in which only one correction factor is needed. This scheme is then applied to tens of water clusters to calculate the three- and four-body interaction energies. The three-body interaction energies of 93 water clusters produced by our scheme are compared with those produced by the counterpoise-corrected CCSD(T)/aug-cc-pVDZ, MP2/aug-cc-pVDZ, M06-2X/jul-cc-pVTZ methods, by the AMOEBApro13, iAMOEBA, AMOEBA+, AMOEBA+(CF) methods, and by the MB-pol method. The four-body interaction energies of 47 water clusters yielded by our scheme are compared with those yielded by the counterpoise-corrected MP2/aug-cc-pVDZ and M06-2X/ jul-cc-pVTZ methods, by the AMOEBApro13, AMOEBA+, AMOEBA+(CF) methods, and by the MB-pol method. The comparison results show that the scheme proposed in this paper can reproduce the counterpoise-corrected CCSD(T)/aug-cc-pVDZ three-body interaction energies and reproduce the counterpoise-corrected MP2/aug-cc-pVDZ four-body interaction energies both accurately and efficiently. We anticipate the scheme proposed here can be useful for computer simulations of liquid water and aqueous solutions.

Transition-metal free C-N bond formation from alkyl iodides and diazonium salts via halogen-atom transfer.

Construction of C-N bond continues to be one part of the most significant goals in organic chemistry because of the universal applications of amines in pharmaceuticals, materials and agrochemicals. However, E2 elimination through classic SN2 substitution of alkyl halides lead to generation of alkenes as major side-products. Thus, formation of a challenging C(sp3)-N bond especially on tertiary carbon center remains highly desirable. Herein, we present a practical alternative to prepare primary, secondary and tertiary alkyl amines with high efficiency between alkyl iodides and easily accessible diazonium salts. This robust transformation only employs Cs2CO3 promoting halogen-atom transfer (XAT) process under transition-metal-free reaction conditions, thus providing a rapid method to assemble diverse C(sp3)-N bonds. Moreover, diazonium salts served as alkyl radical initiator and amination reagent in the reaction. Mechanism studies suggest this reaction undergo through halogen-atom transfer process to generate active alkyl radical which couples with diazonium cations to furnish final products.

NBR2/miR-561-5p/DLC1 axis inhibited the development of multiple myeloma by activating the AMPK/mTOR pathway to repress glycolysis.

Long non-coding RNA NBR2 exerts a tumor-suppressive effect in a variety of cancers, but its role in multiple myeloma (MM) is unclear. This article will elucidate the role of NBR2 in MM. The expressions of NBR2, miR-561-5p, and deleted in liver cancer 1 (DLC1) in MM cell lines were determined by quantitative real time polymerase chain reaction (qRT-PCR). The regulatory relationship of the NBR2/miR-561-5p/DLC1 axis was predicted by bioinformatics and confirmed via a dual-luciferase reporter assay. The effect of NBR2 on the biological behavior of MM cells was verified by loss- and gain-of-function experiments (cell counting kit-8, colony formation, flow cytometry, extracellular acidification rate, and lactate production measurement). The effects of the NBR2/miR-561-5p axis on the biological behavior of MM cells, the activation of the AMPK/mTOR signaling pathway (western blot), and DLC1 expression (western blot) were verified by rescue experiments. The upregulation of NBR2 in MM cell lines induced a decrease in the viability, proliferation capacity, glycolysis, and lactic acid production, and an increase in apoptosis of MM cells. NBR2 regulated the biological behavior of MM cells and the activation of the AMPK/mTOR signaling pathway by targeting miR-561-5p. DLC1 was the target gene of miR-561-5p and the protein expression of DLC1 was regulated by the NBR2/miR-561-5p axis. Collectively, NBR2/miR-561-5p/DLC1 axis inhibits the development of MM by activating the AMPK/mTOR pathway to repress glycolysis.

Identifying mutations in sd1, Pi54 and Pi-ta, and positively selected genes of TN1, the first semidwarf rice in Green Revolution.

BACKGROUND: Taichung Native 1 (TN1) is the first semidwarf rice cultivar that initiated the Green Revolution. As TN1 is a direct descendant of the Dee-geo-woo-gen cultivar, the source of the sd1 semidwarf gene, the sd1 gene can be defined through TN1. Also, TN1 is susceptible to the blast disease and is described as being drought-tolerant. However, genes related to these characteristics of TN1 are unknown. Our aim was to identify and characterize TN1 genes related to these traits. RESULTS: Aligning the sd1 of TN1 to Nipponbare sd1, we found a 382-bp deletion including a frameshift mutation. Sanger sequencing validated this deleted region in sd1, and we proposed a model of the sd1 gene that corrects errors in the literature. We also predicted the blast disease resistant (R) genes of TN1. Orthologues of the R genes in Tetep, a well-known resistant cultivar that is commonly used as a donor for breeding new blast resistant cultivars, were then sought in TN1, and if they were present, we looked for mutations. The absence of Pi54, a well-known R gene, in TN1 partially explains why TN1 is more susceptible to blast than Tetep. We also scanned the TN1 genome using the PosiGene software and identified 11 genes deemed to have undergone positive selection. Some of them are associated with drought-resistance and stress response. CONCLUSIONS: We have redefined the deletion of the sd1 gene in TN1, a direct descendant of the Dee-geo-woo-gen cultivar, and have corrected some literature errors. Moreover, we have identified blast resistant genes and positively selected genes, including genes that characterize TN1's blast susceptibility and abiotic stress response. These new findings increase the potential of using TN1 to breed new rice cultivars.

Two genomic regions of a sodium azide induced rice mutant confer broad-spectrum and durable resistance to blast disease.

Rice blast, one of the most destructive epidemic diseases, annually causes severe losses in grain yield worldwide. To manage blast disease, breeding resistant varieties is considered a more economic and environment-friendly strategy than chemical control. For breeding new resistant varieties, natural germplasms with broad-spectrum resistance are valuable resistant donors, but the number is limited. Therefore, artificially induced mutants are an important resource for identifying new broad-spectrum resistant (R) genes/loci. To pursue this approach, we focused on a broad-spectrum blast resistant rice mutant line SA0169, which was previously selected from a sodium azide induced mutation pool of TNG67, an elite japonica variety. We found that SA0169 was completely resistant against the 187 recently collected blast isolates and displayed durable resistance for almost 20 years. Linkage mapping and QTL-seq analysis indicated that a 1.16-Mb region on chromosome 6 (Pi169-6(t)) and a 2.37-Mb region on chromosome 11 (Pi169-11(t)) conferred the blast resistance in SA0169. Sequence analysis and genomic editing study revealed 2 and 7 candidate R genes in Pi169-6(t) and Pi169-11(t), respectively. With the assistance of mapping results, six blast and bacterial blight double resistant lines, which carried Pi169-6(t) and/or Pi169-11(t), were established. The complementation of Pi169-6(t) and Pi169-11(t), like SA0169, showed complete resistance to all tested isolates, suggesting that the combined effects of these two genomic regions largely confer the broad-spectrum resistance of SA0169. The sodium azide induced mutant SA0169 showed broad-spectrum and durable blast resistance. The broad resistance spectrum of SA0169 is contributed by the combined effects of two R regions, Pi169-6(t) and Pi169-11(t). Our study increases the understanding of the genetic basis of the broad-spectrum blast resistance induced by sodium azide mutagenesis, and lays a foundation for breeding new rice varieties with durable resistance against the blast pathogen.

Regio- and Stereoselective Synthesis of Enol Carboxylate, Phosphate, and Sulfonate Esters via Iodo(III)functionalization of Alkynes.

ß-Iodo(III)enol carboxylates, phosphates, and tosylates can be efficiently synthesized through regio- and stereoselective iodo(III)functionalization of alkynes. The combination of chlorobenziodoxole and silver salt has proven to generate a versatile cationic iodine(III) electrophile to activate alkynes and engage various carboxylic acids, triethyl phosphate, and p-toluenesulfonic acid as nucleophiles. The ß-iodo(III)enol esters serve as starting materials for the synthesis of multisubstituted alkenes through sequential cross-coupling of the C-I(III) and C-O bonds.

Understanding the Effect of Conformational Rigidity on Rheological Behavior and Formation of Polysaccharide-Based Hybrid Hydrogels.

The importance of conformational rigidity on macroscopic rheological properties was revealed using two model polysaccharides, namely, xanthan gum and hyaluronic acid. Xanthan gum has a rigid tertiary conformation due to its ordered double-helical structure, and the interactions between the tertiary structures result in the formation of a network/quaternary structure. In comparison, hyaluronic acid possesses a relatively flexible tertiary conformation due to its secondary random coil structure. Xanthan gum exhibits a much stronger shear thinning and more solidlike behavior compared to hyaluronic acid, owing to its network/quaternary structure. The rigid tertiary structure and the presence of a network/quaternary structure also endow xanthan gum with better resistance against environmental changes (e.g., salt and/or urea addition, temperature change) compared to hyaluronic acid. The network/quaternary structure allows xanthan gum to form gels with chitosan via electrostatic interactions when using the vapor-induced gelation technique, which is not possible for hyaluronic acid due to its flexible tertiary conformation under similar conditions.

Chromosomal-level genome assembly of the semi-dwarf rice Taichung Native 1, an initiator of Green Revolution.

Here we report the 409.5 Mb chromosome-level assembly of the first bred semi-dwarf rice, the Taichung Native 1 (TN1), which served as the template for the development of the Green Revolution (GR) cultivar IR8 "miracle rice". We sequenced the TN1 genome utilizing multiple platforms and produced PacBio long reads, Illumina paired-end reads, Illumina mate-pair reads and 10x Genomics linked reads. We used a hybrid approach to assemble the 226× coverage of sequences by a combination of de novo and reference-guided approaches. The assembled TN1 genome has an N50 scaffold size of 33.1 Mb with the longest measuring 45.5 Mb. We annotated 37,526 genes, in which 24,102 (64.23%) were assigned Blast2GO annotations. The genome has 4672 or 95.4% complete BUSCOs and a repeat content of 51.52%. We developed our own method of creating a GR pangenome using the orthologous relationships of the proteins of TN1, IR8, MH63 and IR64, identifying 16,999 core orthologue groups of Green Revolution. From the pangenome, we identified a set of shared and unique gene ontology terms for the accessory clusters, characterizing TN1, IR8, MH63 and IR64. This TN1 genome assembly and GR pangenome will be a resource for new genomic discoveries about Green Revolution, and for improving the disease and insect resistances and the yield of rice.

Point-of-care ultrasound for the early diagnosis of emphysematous pyelonephritis: A case report and literature review.

BACKGROUND: Emphysematous pyelonephritis (EPN) is a rare but fatal necrotic infection of the kidney, which usually leads to septic shock. Therefore, early diagnosis and optimized therapy are of paramount importance. In the past two decades, point-of-care ultrasound (POCUS) has been widely used in clinical practice, especially in emergency and critical care settings, and helps to rapidly identify the source of infection in sepsis. We report a rare case in which a "falls" sign on POCUS played a pivotal role in the early diagnosis of EPN. CASE SUMMARY: A 57-year-old man presented with fever and lumbago for 3 d prior to admission. He went to the emergency room, and the initial POCUS detected gas bubbles in the hepatorenal space showing a hyperechoic focus with dirty shadowing and comet-tail artifacts. This imaging feature was like a mini waterfall. His blood and urine culture demonstrated Escherichia coli bacteremia, and EPN associated with septic shock was diagnosed. The patient did not respond to broad-spectrum antibiotic treatment and a perirenal abscess developed. He subsequently underwent computed tomography-guided percutaneous catheter drainage, and fully recovered. We also review the literature on the sonographic features of POCUS in EPN. CONCLUSION: This case indicates that a "falls" sign on POCUS facilitates the rapid diagnosis of severe EPN at the bedside.

Robust Cobalt Catalyst for Nitrile/Alkyne [2+2+2] Cycloaddition: Synthesis of Polyarylpyridines and Their Mechanochemical Cyclodehydrogenation to Nitrogen-Containing Polyaromatics*.

The transition-metal-catalyzed [2+2+2] cycloaddition of nitriles and alkynes is an established synthetic approach to pyridines; however, these cycloadditions often rely on the use of tethered diynes or cyanoalkynes as one of the reactants. Thus, examples of efficient, fully intermolecular catalytic [2+2+2] pyridine synthesis, especially those employing unactivated nitriles and internal alkynes leading to pentasubstituted pyridines, remain scarce. Herein, we report on simple and inexpensive catalytic systems based on cobalt(II) iodide, 1,3-bis(diphenylphosphino)propane, and Zn that promote [2+2+2] cycloaddition of various nitriles and diarylacetylenes for the synthesis of a broad range of polyarylated pyridines. DFT studies support a reaction pathway involving oxidative coupling of two alkynes, insertion of the nitrile into a cobaltacyclopentadiene, and C-N reductive elimination. The resulting tetra- and pentaarylpyridines serve as precursors to hitherto unprecedented nitrogen-containing polycyclic aromatic hydrocarbons via mechanochemically assisted multifold reductive cyclodehydrogenation.

Cobalt/Lewis Acid Catalysis for Hydrocarbofunctionalization of Alkynes via Cooperative C-H Activation.

A catalytic system comprising a cobalt-diphosphine complex and a Lewis acid (LA) such as AlMe3 has been found to promote hydrocarbofunctionalization reactions of alkynes with Lewis basic and electron-deficient substrates such as formamides, pyridones, pyridines and related azines, imidazo[1,2-a]pyridines, and azole derivatives through site-selective C-H activation. Compared with known Ni/LA catalytic systems for analogous transformations, the present catalytic systems not only feature convenient setup using inexpensive and bench-stable precatalyst and ligand such as Co(acac)3 and 1,3-bis(diphenylphosphino)propane (dppp) but also display distinct site-selectivity toward C-H activation of pyridone and pyridine derivatives. In particular, a completely C4-selective alkenylation of pyridine has been achieved for the first time. Meanwhile, the present catalytic system proved to promote exclusively C5-selective alkenylation of imidazo[1,2-a]pyridine derivatives. Mechanistic studies including DFT calculations on the Co/Al-catalyzed addition of formamide to alkyne have suggested that the reaction involves cleavage of the carbamoyl C-H bond as the rate-limiting step, which proceeds through a ligand-to-ligand hydrogen transfer (LLHT) mechanism leading to an alkenyl(carbamoyl)cobalt intermediate.