Rh(III)-catalyzed [4 + 1] annulation of 1-arylindazolones with alkynyl cyclobutanols: access to indazolo[1,2-a]indazolones.

A convenient and efficient synthesis of structurally diverse indazolo[1,2-a]indazolones via a Rh(III)-catalyzed [4 + 1] annulation of 1-arylindazolones with alkynyl cyclobutanols has been achieved by combining C-H and C-C bond cleavage. This cascade reaction features readily available starting materials, good functional group tolerance, broad substrate scope, and excellent atom-economy.

Four-Component Radical 1,2-Selenosulfonylation of Allenes.

Selenosulfones, as pivotal pharmaceutical molecule frameworks, have become a research hotspot in modern organic synthesis due to their vital need for efficient preparation. Herein, we have developed an iron-catalyzed four-component controllable radical tandem reaction of allenes involving cycloketone oxime esters, 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide) adduct (DABSO), and diphenyl diselenides for the synthesis of complex selenosulfones. This is the first case of achieving the 1,2-selenosulfonylation of allenes via a radical process, wherein precise control of radical rates and polarity matching enhance high regioselective conversion. The reaction conditions are ecofriendly and mild with step-efficiency by forming two new C-S bonds and one C-Se bond in one pot. Moreover, the 1,2-selenosulfonylation of allenes can be achieved by replacing cycloketone oxime esters with aryldiazonium tetrafluoroborates in this system.

Chi-miR-3880 mediates the regulatory role of interferon gamma in goat mammary gland.

A healthy mammary gland is a necessity for milk production of dairy goats. The role of chi-miR-3880 in goat lactation is illustrated in our previous study. Among the differentially expressed genes regulated by chi-miR-3880, one seventh were interferon stimulated genes, including MX1, MX2, IFIT3, IFI44L, and DDX58. As the inflammatory cytokine interferon gamma (IFNγ) has been identified as a potential marker of caseous lymphadenitis in lactating sheep, the interaction between IFNγ and immune-related microRNAs was explored in this study. Chi-miR-3880 was found to be one of the microRNAs downregulated by IFNγ in goat mammary epithelial cells (GMECs). The study illustrated that IFNγ/chi-miR-3880/DDX58 axis modulates GMEC proliferation and lipid formation through PI3K/AKT/mTOR pathway, and regulates apoptosis through Caspase-3 and Bcl-2/Bax pathways. The role of the axis in mammary involution was reflected by the expression of p53 and NF-κB. In conclusion, IFNγ/chi-miR-3880/DDX58 axis plays an important part in lactation.

Integrated Network Pharmacology and Proteomic Analyses of Targets and Mechanisms of Jianpi Tianjing Decoction in Treating Vascular Dementia.

Background: Vascular dementia (VD), associated with cerebrovascular injury, is characterized by severe cognitive impairment. Jianpi Tianjing Decoction (JTD) has been widely used to treat VD. However, its molecular targets and mechanisms of action in this treatment remain unclear. This study integrated network pharmacology and proteomics to identify targets and mechanisms of JTD in the treatment of VD and to provide new insights and goals for clinical treatments. Methods: Systematic network pharmacology was used to identify active chemical compositions, potential targets, and mechanisms of JTD in VD treatment. Then, a mouse model of VD was induced via transient bilateral common carotid artery occlusion to verify the identified targets and mechanisms of JTD against VD using 4D label-free quantitative proteomics. Results: By screening active chemical compositions and potential targets in relevant databases, 187 active chemical compositions and 416 disease-related compound targets were identified. In vivo experiments showed that JTD improved learning and memory in mice. Proteomics also identified 112 differentially expressed proteins in the model and sham groups and the JTD and model groups. Integrating the network pharmacology and proteomics results revealed that JTD may regulate expressions of cytochrome c oxidase subunit 7C, metabotropic glutamate receptor 2, Slc30a1 zinc transporter 1, and apolipoprotein A-IV in VD mice and that their mechanisms involve biological processes like oxidative phosphorylation, regulation of neuron death, glutamate secretion, cellular ion homeostasis, and lipoprotein metabolism. Conclusions: JTD may suppress VD development via multiple components, targets, and pathways. It may thus serve as a complementary treatment option for patients with VD.

Three-Component Synthesis of Isoquinolone Derivatives via Rh(III)-Catalyzed C-H Activation and Tandem Annulation.

A one-pot three-component synthesis of multifunctionalized isoquinolones from 2-oxazolines, iodonium ylides, and carboxylic acids via Rh(III)-catalyzed oxazolinyl-directed C-H activation and tandem annulation under redox-neutral conditions has been developed. This catalytic system is characterized by readily available starting materials, a wide tolerance of functional groups, a short reaction time, and high yields. The synthetic utility of the cascade reaction was further demonstrated by a gram-scale synthesis and derivatization of the obtained products.

Learning Curve and Complications of Unilateral Biportal Endoscopy: Cumulative Sum and Risk-Adjusted Cumulative Sum Analysis.

OBJECTIVE: The purpose of this study was to investigate the learning curve and complications of unilateral biportal endoscopy (UBE) in the treatment of lumbar disc herniation (LDH) and lumbar spinal stenosis (LSS). METHODS: This was a retrospective cohort analysis of 197 consecutive patients who received UBE unilateral laminotomy bilateral decompression (UBE-ULBD) or lumbar discectomy (UBE-LD) surgery, including 107 males and 90 females with an average age of 64.83 ± 14.29 years. Cumulative sum (CUSUM) and risk-adjusted cumulative sum analysis (RA-CUSUM) were used to evaluate the learning curve, with the occurrence of complications defined as surgical failure, and variables of different phase of the learning curve were compared. RESULTS: The cutoff point of learning curve of UBE surgery was 54 cases according to CUSUM analysis. The learning curve of UBE-ULBD and UBE-LD were divided into 3 phases. The first cutoff points were 31 and 12 cases, and the second cutoff point were 67 and 32 cases respectively. With the progress of the learning curve, the operation time and postoperative hospital stays decreased. The visual analogue scale and Oswestry Disability Index at the last follow-up were significantly lower than that before surgery. The incidence of surgical failure was 6.11% and began to decrease after the 89th case based on RA-CUSUM analysis. The surgical failure rate decreased from 10.11% to 2.78 after the 89th case with significant different. CONCLUSION: UBE surgery is effective in the treatment of LDH and LSS with low incidence of complications. But a learning curve of at least 54 cases still required for mastering UBE surgery.

Rhodium(III)-catalyzed oxidative annulation of isoquinolones with allyl alcohols: synthesis of isoindolo[2,1-b]isoquinolin-5(7H)-ones.

An efficient rhodium(III)-catalyzed direct C-H oxidative annulation of isoquinolones with allyl alcohols as C1 synthons has been successfully developed. This protocol enables the straightforward synthesis of structurally diverse isoindolo[2,1-b]isoquinolin-5(7H)-ones with high atom economy, tolerates a broad spectrum of functionalities, and is applicable to one-pot operation from readily available N-methoxybenzamides.

EGF-Induced miR-223 Modulates Goat Mammary Epithelial Cell Apoptosis and Inflammation via ISG15.

The health of mammary gland is essential for lactation. Epidermal growth factor (EGF) is reported to play an important role in lactation initiation and miR-223 is a conserved microRNA in anti-inflammation. In this study, EGF was found to induce a higher expression of miR-223 in goat mammary epithelial cell (gMEC). The downstream genes of miR-223 were screened by RNA sequencing, including Interferon-stimulated gene product 15 (ISG15), a pivotal immune responder, which was detected to be downregulated by EGF and miR-223. Due to the correlation between inflammation and apoptosis, the gMEC apoptosis modulated by EGF, miR-223, and ISG15 was investigated, and the protein expressions of Bcl-2/Bax, Caspase 3 and p53 were examined to evaluate the apoptosis of gMEC. The protein expressions of p-STAT3/STAT3, PR, FOXC1, and HOXA10, which had been shown to be related to inflammation, were detected to assess the inflammation of gMEC. This study provided a regulation axis, EGF/miR-223/ISG15, and illustrated its regulation to gMEC apoptosis and inflammation.

Rhodium(III)-Catalyzed Oxidative Cyclization of Oxazolines with Cyclopropanols: Synthesis of Isoindolinones.

The synthesis of C3-substituted isoindolin-1-ones from oxazolines and cyclopropanols has been achieved with oxazoline as a bifunctional nucleophilic directing group. The reaction proceeds by the cleavage of three chemical bonds and allows the formation of three new chemical bonds, a C-N bond, a C-C bond, and a C-O bond, in a single step.

Circ-140/chi-miR-8516/STC1-MMP1 Regulates αs1-/ß-Casein Secretion and Lipid Formation in Goat Mammary Epithelial Cells.

MicroRNAs play an essential role in mammary gland development, and involution is a factor that limits lactation. Chi-miR-8516 is one of the validated microRNAs that regulates the expression of STC1 and MMP1, which surge during the involution of the mammary gland. This study aims to explore the direct or indirect regulation of STC1 and MMP1 by chi-miR-8516 and the regulation of chi-miR-8516 by circ-140. In goat mammary epithelial cells, we found that chi-miR-8516 takes circ-140 as a sponge and regulates MMP1 expression by targeting STC1 and promoting the phosphorylation of MAPK. The examination of αs1-/ß-casein and lipid showed the modulation of the circ-140/chi-miR-8516/STC1-MMP1 axis in casein secretion and lipid formation, which was regulated by the phosphorylation of mTOR and STAT5. This study illustrates an axis that regulates the synthesis of milk components, and explores the pathways in which the axis participates.

Correction: Rhodium(iii)-catalyzed oxidative alkylation of N-aryl-7-azaindoles with cyclopropanols.

Correction for 'Rhodium(iii)-catalyzed oxidative alkylation of N-aryl-7-azaindoles with cyclopropanols' by Jidan Liu et al., Org. Biomol. Chem., 2021, DOI: .

Rhodium(III)-catalyzed oxidative alkylation of N-aryl-7-azaindoles with cyclopropanols.

An efficient Rh(iii)-catalyzed C-H oxidative alkylation of N-aryl-7-azaindoles with cyclopropanols by merging tandem C-H and C-C cleavage was developed. This transformation features mild reaction conditions, high regioselectivity, and excellent functional group compatibility. The resulting ß-aryl ketone derivatives can be readily transformed into 7-azaindole-containing π-extended polycyclic heteroarenes.

Effects of rhodioloside on the neurological functions of rats with total cerebral ischemia/reperfusion and cone neuron injury in the hippocampal CA1 region.

Rhodioloside, the main effective constituent of Rhodiola rosea, demonstrates antiaging and antioxidative stress functions and inhibits calcium overloading in cells. These functions imply that rhodioloside may exert protective effects on hippocampal neurons after total cerebral ischemia/reperfusion injury. In this study, male Wistar rat models of total cerebral ischemia were constructed and randomly divided into four groups: sham-operation, ischemia/reperfusion, low-dosage, and high-dosage groups. The result showed that rhodioloside treatment reduced the apoptosis rates of hippocampal neurons and the histological grades of cone cells in the hippocampal CA1 region, but neuronal density was significantly increased. Besides, the protein expressions of Bcl-2/Bax and p53 were measured and found Bcl-2/Bax was increased and p53 protein level was reduced. Therefore, rhodioloside might have protective effects on rats with ischemia/reperfusion brain injury.

A Regulatory Circuit Orchestrated by Novel-miR-3880 Modulates Mammary Gland Development.

Milk casein and triglyceride content are important production traits in goats. Studies on mechanisms in milk casein secretion and mammary gland development is essential for milk goat breeding. miRNAs play an important role in goat lactation. While novel-miR-3880 is highly expressed at goat peak lactation stage, its molecular mechanism has not been studied. The purpose of the present study was to explore the relationship between novel-miR-3880 and lactation, as well as to construct a network among novel-miR-3880, ciRNA13761, and E74 like ETS transcription factor 2 (ELF2), thus further exploring their potential roles in milk components and mammary gland development. ELF2 was previously proven to be important in cell survival and proliferation, and 3'-UTR of ELF2 was predicted to have binding sites of novel-miR-3880. Our study found that the overexpression of novel-miR-3880 exerted anti-apoptotic and proliferative roles in GMEC, induced a boost in triglyceride synthesis, and caused a decrease in α s1-, α s2-, and ß-casein, but an increase in κ-casein secretion. Furthermore, treatment in mice indicated that novel-miR-3880 could promote mammary gland development and extend the lactation period, while novel-miR-3880 expression was found to be suppressed by ciRNA13761 as a miRNA sponge. The present study explores a mechanism of triglyceride synthesis and casein secretion, and reveals a crosstalk between ciRNA13761/novel-miR-3880/ELF2 axis and PI3K/AKT/mTOR/S6K1 pathway, to gain a better understanding of lactation traits in dairy goats.

Copper-mediated tandem ring-opening/cyclization reactions of cyclopropanols with aryldiazonium salts: synthesis of N-arylpyrazoles.

A general method for the synthesis of structurally diverse N-arylpyrazoles from readily available cyclopropanols and aryldiazonium salts is disclosed. The reaction was conducted at room temperature within minutes with a broad substrate scope and excellent regioselectivity.

Synthesis of Multisubstituted 1-Naphthoic Acids via Ru-Catalyzed C-H Activation and Double-Alkyne Annulation under Air.

An efficient [2 + 2 + 2] benzannulation of phthalic acids/anhydrides with two alkynes was developed for synthesis of multisubstituted 1-naphthoic acids via Ru-catalyzed C-H activation. The reaction preceded well using atmospheric oxygen as the sole oxidant with high atom/step economies. Facilitated by the free carboxyl group, the products can be easily converted to diverse polycyclic molecules.

Metal-free synthesis of imidazo[1,5-a]pyridines via elemental sulfur mediated sequential dual oxidative Csp3-H amination.

A simple and efficient approach has been developed for the synthesis of imidazo[1,5-a]pyridines using the elemental sulfur mediated sequential dual oxidative Csp3-H amination of 2-pyridyl acetates and amines under metal- and peroxide-free conditions. Broad substrate scope, operational simplicity and gram-scale ability make this chemistry very practical.

Photocatalytic/Cu-Promoted C-H Activations: Visible-light-Induced ortho-Selective Perfluoroalkylation of Benzamides.

A visible-light-induced and copper-promoted perfluoroalkylation of benzamides was successfully developed under the assistance of an 8-aminoquinoline directing group. It provides a straightforward method for the synthesis of ortho-perfluoroalkyl-substituted benzoic acid derivatives. The reaction employs a cheap organic dye eosin Y as the photoredox catalyst and is run under the irradiation of a 26 W fluorescent LED light bulb.

Stereoselective synthesis of vinylphosphonates and phosphine oxides via silver-catalyzed phosphorylation of styrenes.

An efficient and stereoselective synthesis of vinylphosphonates and phosphine oxides was developed starting from styrenes using AgNO3 as the catalyst and K2S2O8 as the oxidant. The success of the reaction was found to be critically dependent on the use of TEMPO as the additive.

Copper-mediated ortho C-H sulfonylation of benzoic acid derivatives with sodium sulfinates.

Copper-mediated direct ortho C-H bond sulfonylation of benzoic acid derivatives with sodium sulfinates was achieved by employing an 8-aminoquinoline moiety as the bidentate directing group. Various aryl sulfones were synthesized in good yields with excellent regioselectivity.