Catalytic enantioselective reductive alkynylation of amides enables one-pot syntheses of pyrrolidine, piperidine and indolizidine alkaloids.

The primary objective in synthetic organic chemistry is to develop highly efficient, selective, and versatile synthetic methodologies, which are essential for discovering new drug candidates and agrochemicals. In this study, we present a unified strategy for a one-pot, catalytic enantioselective synthesis of α-alkyl and α,α'-dialkyl pyrrolidine, piperidine, and indolizidine alkaloids using readily available amides and alkynes. This synthesis is enabled by the identification and development of an Ir/Cu/N-PINAP catalyzed highly enantioselective and chemoselective reductive alkynylation of α-unbranched aliphatic amides, which serves as the key reaction. This reaction is combined with Pd-catalyzed tandem reactions in a one-pot approach, enabling the collective, catalytic enantioselective total syntheses of eight alkaloids and an anticancer antipode with 90-98% ee. The methodology's enantio-divergence is exemplified by the one-step access to either enantiomer of alkaloid bgugaine.

The efficacy of ankle arthroplasty on motor function recovery in patients with orthopedic ankle injury: a systematic review and meta-analysis.

BACKGROUND: This study analyzed the effects of ankle arthroplasty on the recovery of motor function in patients with orthopedic ankle injury. METHODS: English databases including PubMed, Web of Science, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) examining the effects of ankle arthroplasty, ankle replacement, and joint prosthesis on motor function recovery in patients with orthopedic ankle injury. The outcome indicators included the American Orthopedic Foot and Ankle Society (AOFAS) score, the 36-item short form survey (SF-36) score, the Foot and Ankle Ability Measures (FAAM) score, and the visual analog scale (VAS) score. The quality of the included literature was evaluated using the Jadad tool, and meta-analysis of the experimental data was performed using the Review Manager 5.3 software. RESULTS: A total of 7 articles, including 443 patients, were analyzed. The meta-analysis showed significant improvement in AOFAS scores among patients in the experiment group (who underwent ankle replacement) compared with those in the control group (who did not undergo ankle replacement) [mean difference (MD) =-41.89, 95% confidence interval (CI): -51.29 to 32.49, Z=8.73, P<0.00001], VAS scores (MD =5.59, 95% CI: 4.84 to 6.34, Z=14.56, P<0.00001), SF-36 scores (MD =-13.89, 95% CI: -26.74 to 1.04, Z=2.12, P=0.03), and FAAM scores (MD =-25.78, 95% CI: -31.27 to 20.29, Z=9.20, P<0.00001) compared to patients in the control group. DISCUSSION: Ankle arthroplasty had a positive effect on the quality of life, daily activities, and motor function recovery of patients with orthopedic ankle injuries. While ankle arthroplasty has potential for clinical application, future high-quality, long-term studies with larger samples and more outcome indicators are warranted to verify these results.

[Analysis of Nitrogen Transformation Characteristics and Influencing Factors of Forestland Soil in the Qinghai-Tibet Plateau: A Case Study of the Qilian Mountains and Southeast Tibet].

Mineralization and nitrification, two important processes of the N cycle in forest ecosystems, play an important role in the maintenance of ecosystem function and soil environmental quality. The net mineralization rate and net nitrification rate are two common indexes for evaluation of the N supply and N loss risk in soil. In order to study the soil N transformation characteristics and their influencing factors in woodlands of the Qinghai-Tibet Plateau, the inorganic N concentrations, net N mineralization rates, and net nitrification rates of 327 soils sampled from the Qilian Mountains and Southeast Tibet were analyzed using indoor incubation experiments. The results showed that the inorganic N concentration, net N mineralization rate, and net nitrification rate of the woodland soil in Southeast Tibet ï¼»109.70 mg·kg-1, 3.08 mg·(kg·d)-1, and 2.19 mg·(kg·d)-1ï¼½ were significantly higher than those in the Qilian Mountains ï¼»49.47 mg·kg-1, 0.70 mg·(kg·d)-1, and 0.69 mg·(kg·d)-1ï¼½. The net mineralization rate of soil was positively correlated with the mean annual temperature (MAT), mean annual precipitation (MAP), moisture index, and soil organic matter concentrations (P<0.001). There were no significant positive relationships between the net nitrification rate and the MAT and MAP, but the net nitrification rate was positively correlated with the net N mineralization rate (P<0.001). These results indicated that the N supply ability of woodland soil in Southeast Tibet is significantly higher than that in the Qilian Mountains, and the hydrothermal conditions (MAT and MAP) are likely responsible for the difference in the net mineralization rate between the two studied regions. The net mineralization rate is the limiting factor for the net nitrification rate, which has an important influence on the spatial distribution of the forest soil nitrification process in the Qinghai-Tibet Plateau. These results emphasize the important roles of climatic and environmental factors, such as hydrothermal conditions, on the net N mineralization and nitrification rates of woodland soil in the Qinghai-Tibet Plateau, and will further deepen the understanding of the law of soil N transformation in woodlands in the Qinghai-Tibet Plateau.

MicroRNA-370 protects against myocardial ischemia/reperfusion injury in mice following sevoflurane anesthetic preconditioning through PLIN5-dependent PPAR signaling pathway.

Myocardial ischemia/reperfusion injury (IRI) has long been identified to be a contributor to adverse cardiovascular outcomes following myocardial ischemia, cardiac surgery or circulatory arrest. This study aims to investigate the effects of microRNA (miR-370) targeting perilipin-5 (PLIN5) in mice following sevoflurane anesthetic preconditioning (SAP). A mouse model of left ventricular myocardial IRI was established, followed by the evaluation of myocardial infarction size and cardiac function to determine the effects of SAP. The underlying regulatory mechanisms of miR-370 were analyzed in concert with the treatment of miR-370 mimic, miR-370 inhibitor, or siRNA against PLIN5 in cardiomyocytes isolated from mice with IRI. Also, cardiomyocyte proliferation, cell cycle distribution and apoptosis were evaluated following treatment. Lastly, SAP-treated I/R mice were injected with miR-370 inhibitor to verify the mechanism of SAP. The use of SAP conferred cardioprotective effects on myocardial IRI. MiR-370 was downregulated in mice that exhibited IRI, but SAP elevated the miR-370 expression. Functionally, miR-370 negatively targeted PLIN5 and activated the peroxisome proliferator activated-receptor (PPAR) signaling pathway, leading to decreased PPARγ expression but increased PPARα expression. The results also showed that elevation of miR-370 or the silencing of PLIN5 promoted cardiomyocyte proliferation. miR-370 also inhibited cardiomyocyte apoptosis as reflected by decreased caspase-3 expression and increased Bcl-2 expression. Additionally, SAP also alleviated I/R injury by inhibiting PPARγ. This study demonstrates that SAP induces miR-370 and exerts cardioprotective effects on myocardial IRI, where upregulation of miR-370 alleviates myocardial IRI via inhibiting the PLIN5-dependent PPAR signaling pathway.

Construction of the tetracyclic core of (±)-cycloclavine and 4-amino Uhle's ketone.

A rapid construction of the tetracyclic core (±)-2 of (±)-cycloclavine (1) was accomplished in seven steps and 24% overall yield from commercially available aldehyde 7. Key features include a domino Friedel-Crafts/nitro-Michael reaction to construct the C ring and an intramolecular ammonolysis of a diester to close the D ring. In addition, a versatile 4-amino Uhle's ketone (±)-3 was afforded rapidly in five steps and 43% overall yield.

A ratiometric mitochondria-targeting two-photon fluorescent probe for imaging of nitric oxide in vivo.

A two-photon ratiometric fluorescent probe (Mito-N) has been developed for monitoring mitochondrial nitric oxide (NO) in vivo. Mito-N exhibited excellent selectivity and sensitivity toward NO among various ROS/RNS. The successful two-photon imaging of mitochondrial NO proved that Mito-N is a powerful noninvasive imaging tool in living systems.

Asymmetric formal synthesis of (+)-cycloclavine.

The asymmetric synthesis of Szántay's amine (+)-2, the pivotal precursor for direct access to (+)-cycloclavine (1), is described for the first time in eleven steps with 19.7% overall yield from the commercially available 4-bromoindole. The strategy features an asymmetric induction by Ellman's sulfinimine and rhodium-catalysed isomerization of the C[double bond, length as m-dash]C bond.

[Fluorescence Properties of Single-Trp Peptide: Response to pH and Metal Ions].

Considering the important role of metal ions including copper ions are playing in human body, a novel single-Trp peptide WDAHSS was designed and synthesized in this study to achieve sensitive detection of copper ions via fluorescence spectroscopy. The intrinsic fluorescence of a tryptophan residue in WDAHSS, which was the only source of the molecular fluorescence, could be easily quenched with copper ions. By comparing fluorescence spectra of WDAHSS with those of tryptophan molecules at different pH values, the quenching mechanism of WDAHSS was explored in detail. Research showed that the histidine in WDAHSS bound copper ions with metal coordination. With participation of peptide bond, a square planar structure was formed. It was a consequent chelation of copper ions that caused the quenching of tryptophan residue. At the same time, this study discussed how pH conditions affected the fluorescence spectra of WDAHSS. Furthermore, association constants of copper ions towards WDAHSS were calculated through fluorescence measurements and fitting analyses. To enhance the anti-jamming ability to pH variation, the amino terminal of WDAHSS was intentionally acetylized, leading to a stable fluorescence emission under physiological pH conditions. Besides, WDAHSS was designed as a special structure to enhance the selectivity and biocompatibility of its sensitive detection of copper ions. Further studies on WDAHSS may help to improve the fluorescence imaging detection in vivo.

Abundance and diversity of archaeal accA gene in hot springs in Yunnan Province, China.

It has been suggested that archaea carrying the accA gene, encoding the alpha subunit of the acetyl CoA carboxylase, autotrophically fix CO2 using the 3-hydroxypropionate/4-hydroxybutyrate pathway in low-temperature environments (e.g., soils, oceans). However, little new information has come to light regarding the occurrence of archaeal accA genes in high-temperature ecosystems. In this study, we investigated the abundance and diversity of archaeal accA gene in hot springs in Yunnan Province, China, using DNA- and RNA-based phylogenetic analyses and quantitative polymerase chain reaction. The results showed that archaeal accA genes were present and expressed in the investigated Yunnan hot springs with a wide range of temperatures (66-96 °C) and pH (4.3-9.0). The majority of the amplified archaeal accA gene sequences were affiliated with the ThAOA/HWCG III [thermophilic ammonia-oxidizing archaea (AOA)/hot water crenarchaeotic group III]. The archaeal accA gene abundance was very close to that of AOA amoA gene, encoding the alpha subunit of ammonia monooxygenase. These data suggest that AOA in terrestrial hot springs might acquire energy from ammonia oxidation coupled with CO2 fixation using the 3-hydroxypropionate/4-hydroxybutyrate pathway.

Highly enantioselective aldol reactions between acetaldehyde and activated acyclic ketones catalyzed by chiral primary amines.

Highly enantioselective cross-aldol reactions between acetaldehyde and activated acyclic ketones are reported for the first time. Various acyclic ketones, such as saturated and unsaturated keto esters, reacted with acetaldehyde in the presence of a chiral primary amine and a Brønsted acid to afford optically enriched tertiary alcohols in good yields and with excellent enantioselectivities. Trifluoromethyl ketones were tolerable under the reaction conditions, thereby affording the trifluoromethyl carbinol in good-to-excellent yields and enantioselectivities. Structural modification of the chiral amines from the same chiral source switched the stereoselectivity of the products. The utility of aldol chemistry was demonstrated in the brief synthesis of functionally enriched δ-lactones. Theoretical calculations on the transition-state structure indicated that the protonated tertiary amine could effectively activate the carbonyl group of a keto ester to promote the addition process through hydrogen-bonding interaction and, simultaneously, provide an appropriate attacking pattern for the approach of the keto ester to the enamine, which is formed from acetaldehyde and the chiral catalyst, on a particular face, resulting in high enantioselectivity.

Bacterial and archaeal diversities in Yunnan and Tibetan hot springs, China.

Thousands of hot springs are located in the north-eastern part of the Yunnan-Tibet geothermal zone, which is one of the most active geothermal areas in the world. However, a comprehensive and detailed understanding of microbial diversity in these hot springs is still lacking. In this study, bacterial and archaeal diversities were investigated in 16 hot springs (pH 3.2-8.6; temperature 47-96°C) in Yunnan Province and Tibet, China by using a barcoded 16S rRNA gene-pyrosequencing approach. Aquificae, Proteobacteria, Firmicutes, Deinococcus-Thermus and Bacteroidetes comprised the large portion of the bacterial communities in acidic hot springs. Non-acidic hot springs harboured more and variable bacterial phyla than acidic springs. Desulfurococcales and unclassified Crenarchaeota were the dominated groups in archaeal populations from most of the non-acidic hot springs; whereas, the archaeal community structure in acidic hot springs was simpler and characterized by Sulfolobales and Thermoplasmata. The phylogenetic analyses showed that Aquificae and Crenarchaeota were predominant in the investigated springs and possessed many phylogenetic lineages that have never been detected in other hot springs in the world. Thus findings from this study significantly improve our understanding of microbial diversity in terrestrial hot springs.

Diethyl 4-meth-oxyoxalyl-3,5-diphenyl-pyrrolidine-2,2-dicarboxyl-ate.

In the title compound, C(25)H(27)NO(7), the pyrrolidine ring exhibits an envelope conformation and the benzene rings form a dihedral angle of 33.47 (11)°. In the crystal, pairs of N-H⋯O hydrogen bonds link the mol-ecules into centrosymmetric dimers. Weak C-H⋯O inter-actions link the dimers into layers parallel to the bc plane.

[Expressions of Sca-1, CD24 and Muc1 in quiescent mammary glands of female rats].

OBJECTIVE: To investigate the expressions of the stem cell antigen-1 (Sca-1), Mucin1 (Muc1) and CD24 in quiescent mammary glands of female rats. METHODS: The expressions of CD24 and Sca-1 were detected in 6- and 9-week-old female rat mammary gland by Western blotting. Sections (4 microm) of 6- and 9-week-old female SD rat mammary gland were prepared to observe the expressions of Sca-1, Muc1 and CD24 by immunohistochemical labeling and immunofluorescence labeling. RESULTS: CD24 and Sca-1 in the mammary glands were expressed at lower level in 6-week-old female rats than in 9-week-old female rats. Sca-1 expression was detected in the mammary gland ductus, branching ductus, and areas surrounding the gland alveolus; CD24 was expressed in the mammary gland branching ductus and fat pads, and also the regions surrounding the gland alveolus. Muc1 expression was localized in the mammary gland ductus and branching ductus. CONCLUSIONS: Sca-1-, CD24- and Muc1-positive cells may represent mammary gland progenitor cells, mammary gland stem cells, and mammary gland mature epithelium cells, respectively. This study provides some morphological evidences for identifying these cells, but they still need further verifications in cellular transplantation experiments.