Enantiospecific Analysis of Carboxylic Acids Using Cinchona Alkaloid Dimers as Chiral Solvating Agents.

Cinchona alkaloid derivatives as Brønsted base catalysts have attracted considerable attention in the field of asymmetric catalysis. However, their potential application as chiral solvating agents has not been described. In this research, we investigated the use of the Cinchona alkaloid dimer, namely, (DHQ)2PHAL, as a chiral solvating agent for discerning various mandelic acid derivatives through 1H NMR spectroscopy. The addition of catalytic amounts of DMAP facilitated this process. Our experimental results demonstrate that dimeric (DHQ)2PHAL exhibits remarkable chiral discrimination properties regarding the diagnostic split protons of 1H NMR signals (including 24 examples, up to 0.321 ppm). Furthermore, it serves as an excellent chiral discriminating agent and provides good resolution for racemic chiral phosphoric acid as determined by 31P NMR spectroscopy. The quality of enantiodifferentiation has also been evaluated by means of the parameter "resolution (Rs)". Significantly, this class of CSAs based on (alkaloid)2linker systems with an azaaromatic linker can be directly employed, which is commercially available in an enantiopure form at very low cost and exhibits promising potential in determining the enantiopurity of α-hydroxy acids by chemoselective and biocatalytic reactions.

Enantioselective synthesis of 4-aryl-3,4-dihydrocoumarins via N-heterocyclic carbene catalyzed ß-arylation/cyclization of α-bromoenals.

4-Aryl-3,4-dihydrocoumarins are one of the most important structural motifs. Herein, we disclose an enantioselective N-heterocyclic carbene catalyzed ß-arylation/cyclization of α-bromoenals with 3-aminophenols under mild conditions. The protocol allows for the rapid preparation of 4-aryl-3,4-dihydrocoumarins in acceptable yields with good enantioselectivities. The products of this reaction could be converted into chiral diarylpropanoic acid derivatives without erosion of the enantioselectivity.

Ginsenoside Rg1 attenuates cerebral ischemia-reperfusion injury through inhibiting the inflammatory activation of microglia.

It is recognized that the cerebral ischemia/reperfusion (I/R) injury triggers inflammatory activation of microglia and supports microglia-driven neuronal damage. Our previous studies have shown that ginsenoside Rg1 had a significant protective effect on focal cerebral I/R injury in middle cerebral artery occlusion (MCAO) rats. However, the mechanism still needs further clarification. Here, we firstly reported that ginsenoside Rg1 effectively suppressed the inflammatory activation of brain microglia cells under I/R conditions depending on the inhibition of Toll-likereceptor4 (TLR4) proteins. In vivo experiments showed that the ginsenoside Rg1 administration could significantly improve the cognitive function of MCAO rats, and in vitro experimental data showed that ginsenoside Rg1 significantly alleviated neuronal damage via inhibiting the inflammatory response in microglia cells co-cultured under oxygen and glucose deprivation/reoxygenation (OGD/R) condition in gradient dependent. The mechanism study showed that the effect of ginsenoside Rg1 depends on the suppression of TLR4/MyD88/NF-κB and TLR4/TRIF/IRF-3 pathways in microglia cells. In a word, our research shows that ginsenoside Rg1 has great application potential in attenuating the cerebral I/R injury by targeting TLR4 protein in the microglia cells.

Comparison of instrumented and stand-alone lateral lumbar interbody fusion for lumbar degenerative disease: a systematic review and meta-analysis.

BACKGROUND: Both instrumented and stand-alone lateral lumbar interbody fusion (LLIF) have been widely used to treat lumbar degenerative disease. However, it remains controversial as whether posterior internal fixation is required when LLIF is performed. This meta-analysis aims to compare the radiographic and clinical results between instrumented and stand-alone LLIF. METHODS: PubMed, EMBASE and Cochrane Collaboration Library up to March 2023 were searched for studies that compared instrumented and stand-alone LLIF in the treatment of lumbar degenerative disease. The following outcomes were extracted for comparison: interbody fusion rate, cage subsidence rate, reoperation rate, restoration of disc height, segmental lordosis, lumbar lordosis, visual analog scale (VAS) scores of low-back and leg pain and Oswestry Disability Index (ODI) scores. RESULTS: 13 studies involving 1063 patients were included. The pooled results showed that instrumented LLIF had higher fusion rate (OR 2.09; 95% CI 1.16-3.75; P = 0.01), lower cage subsidence (OR 0.50; 95% CI 0.37-0.68; P < 0.001) and reoperation rate (OR 0.28; 95% CI 0.10-0.79; P = 0.02), and more restoration of disc height (MD 0.85; 95% CI 0.18-1.53; P = 0.01) than stand-alone LLIF. The ODI and VAS scores were similar between instrumented and stand-alone LLIF at the last follow-up. CONCLUSIONS: Based on this meta-analysis, instrumented LLIF is associated with higher rate of fusion, lower rate of cage subsidence and reoperation, and more restoration of disc height than stand-alone LLIF. For patients with high risk factors of cage subsidence, instrumented LLIF should be applied to reduce postoperative complications.

Ratiometric electrochemical determination of hydroxyl radical based on graphite paper modified with metal-organic frameworks and impregnated with salicylic acid.

Hydroxyl radical (•OH) detection is pivotal in medicine, biochemistry and environmental chemistry. Yet, electrochemical method-specific detection is challenging because of hydroxyl radicals' high reactivity and short half-life. In this study, we aimed to modify the electrode surface with a specific recognition probe for •OH. To achieve this, we conducted a one-step hydrothermal process to fabricate a CoZnMOF bimetallic organic framework directly onto conductive graphite paper (Gp). Subsequently, we introduced salicylic acid (SA) and methylene blue (MB), which easily penetrated the pores of CoZnMOF. By selectively capturing •OH by SA and leveraging the electrochemical signal generated by the reaction product, we successfully developed an electrochemical sensor Gp/CoZnMOF/SA + MB. The prepared sensor exhibited a good linear relationship with •OH concentrations ranging from 1.25 to 1200 nM, with a detection limit of 0.2 nM. Additionally, the sensor demonstrated excellent reproducibility and accuracy due to the incorporation of an internal reference. It exhibited remarkable selectivity for •OH detection, unaffected by other electrochemically active substances. The establishment of this sensor provides a way to construct MOF-modified sensors for the selective detection of other reactive oxygen species (ROS), offering a valuable experimental basis for ROS-related disease research and environmental safety investigations.

Polyarylisocyanides Derived from an Alkyne-Pd(II) Catalyst as Robust Alignment Media with Excellent Enantiodiscimination.

The development of chiral alignment media for measuring anisotropic NMR parameters provides an opportunity to determine the absolute configuration of chiral molecules without the need for derivatization. However, chiral alignment media with a high and robust enantiodiscriminating property for a wide range of chiral molecules are still scarce. In this study, we synthesized cholesterol-end-functionalized helical polyisocyanides from a chiral monomer using a cholesterol-based alkyne-Pd(II) initiator. These stereoregular polyisocyanides form stable and weak anisotropic lyotropic liquid crystals (LLCs) in dichloromethane systems, exhibiting highly optical activities in both single left- and right-handed helices. The preparation process of the media was straightforward, and the aligning property of the LLCs could be controlled by adjusting the concentration and temperature. Using the chiral polyisocyanides, we extracted the residual dipolar coupling for an enantiomeric pair of isopinocampheol (IPC), as well as a number of pharmaceutical molecules, demonstrating excellent enantiodiscriminating properties for a broad range of chiral compounds.

Utilizing Ultra-homogeneous SiOx and Defects to Achieve Interlayer Protection for Lithium Metal Anodes.

The uncontrollable growth and uneven nucleation of lithium metal can be addressed by utilizing spatial confinement structures in conjunction with lithiophilic sites. However, their complex fabrication technique and the inhomogeneous dispersion of lithiophilic sites make the application ineffective. In this work, ultra-uniformly dispersed SiOx seeds and defects are produced in situ to achieve the spatially restricted protection within the reduced graphene oxide (rGO) layer. The in situ formed SiOx and defects during annealing double constrain lithium nucleation and growth behaviors thanks to the superlithiophilic characteristic, while both provide the fast Li+ transport channel to utilize the interlayer protection of rGO in limiting lithium dendrite growth. Furthermore, XANES and XPS analyze the SiOx seeds that are dominated by various valence states, and theoretical calculations further verify the control on the nucleation of lithium atoms. Benefiting from the optimum average valence of three for the "control site", the host realizes steady circulation. In asymmetric cells, the host demonstrates excellent coulombic efficiency of 99.1% and stable lifespans over 1250 h at 1 mA cm-2 . When assembled in LiFePO4 full cells, it retains a favorable capacity of 116.2 mA h g-1 after 170 cycles.

PRMT5 Prevents Dilated Cardiomyopathy via Suppression of Protein O-GlcNAcylation.

[Figure: see text].

Brønsted Acid-Catalyzed Reaction of N-arylnaphthalen-2-amines with Quinone Esters for the Construction of Carbazole and C-N Axially Chiral Carbazole Derivatives.

We demonstrated here an efficient synthetic method of carbazole derivatives from readily available N-arylnaphthalen-2-amines and quinone esters catalyzed by Brønsted acid. With this strategy, a series of carbazole derivatives were obtained in good to excellent yields (76 to >99) under mild conditions. Large scale reaction illustrated the synthetic utility of this protocol. Meanwhile, a series of C-N axially chiral carbazole derivatives were also constructed in moderate to good yields (36-89% yield) with moderate to excellent atroposelectivities (44-94% ee) by using chiral phosphoric acid as a catalyst, which provides a novel strategy for the atroposelective construction of C-N axially chiral compounds and a new member of the C-N atropisomers.

Finite element analysis of the knee joint stress after partial meniscectomy for meniscus horizontal cleavage tears.

OBJECTIVE: To establish a finite element model of meniscus horizontal cleavage and partial resection, to simulate the mechanical changes of knee joint under 4 flexion angles, and to explore what is the optimal surgical plan. METHODS: We used Mimics Research, Geomagic Wrap, and SolidWorks computer software to reconstruct the 3D model of the knee joint, and then produced the horizontal cleavage tears model of the internal and lateral meniscus, the suture model, and the partial meniscectomy model. These models were assembled into a complete knee joint in SolidWorks software, and corresponding loads and boundary constraints were added to these models in ANSYS software to simulate the changing trend of pressure and shear force on femoral condylar cartilage, meniscus, and tibial cartilage under the flexion angles of 0°, 10°, 20°, 30° and 40° of the knee joint. At the same time, the difference of force area between medial interventricular and lateral interventricular of knee joint under four states of bending the knee was compared, to explore the different effects of different surgical methods on knee joint after horizontal meniscus tear. RESULTS: Within the four medial meniscus injury models, the lowest peak internal pressure and shear force of the knee joint was observed in the meniscal suture model; the highest values were found in the bilateral leaflet resection model and the inferior leaflet resection model; the changes of pressure, shear force and stress area in the superior leaflet resection model were the most similar to the changes of the knee model with the meniscal suture model. CONCLUSION: Suture repair is the best way to maintain the force relationship in the knee joint. However, resection of the superior leaflet of the meniscus is also a reliable choice when suture repair is difficult.

A Convex Optimization Approach to Multi-Robot Task Allocation and Path Planning.

In real-world applications, multiple robots need to be dynamically deployed to their appropriate locations as teams while the distance cost between robots and goals is minimized, which is known to be an NP-hard problem. In this paper, a new framework of team-based multi-robot task allocation and path planning is developed for robot exploration missions through a convex optimization-based distance optimal model. A new distance optimal model is proposed to minimize the traveled distance between robots and their goals. The proposed framework fuses task decomposition, allocation, local sub-task allocation, and path planning. To begin, multiple robots are firstly divided and clustered into a variety of teams considering interrelation and dependencies of robots, and task decomposition. Secondly, the teams with various arbitrary shape enclosing intercorrelative robots are approximated and relaxed into circles, which are mathematically formulated to convex optimization problems to minimize the distance between teams, as well as between a robot and their goals. Once the robot teams are deployed into their appropriate locations, the robot locations are further refined by a graph-based Delaunay triangulation method. Thirdly, in the team, a self-organizing map-based neural network (SOMNN) paradigm is developed to complete the dynamical sub-task allocation and path planning, in which the robots are dynamically assigned to their nearby goals locally. Simulation and comparison studies demonstrate the proposed hybrid multi-robot task allocation and path planning framework is effective and efficient.

Construction of N-Ferrocene Substituted Benzodihydrooxazoles via a Catalyst-Free Aza-Michael Addition/C(sp3)-O Bond Formation Tandem Reaction.

A catalyst-free aza-Michael addition/C(sp3)-O bond formation tandem reaction of substituted amino ferrocenes with quinone esters was developed, which provided a green and efficient strategy for the construction of a C(sp3)-O bond from C(sp3)-H, and a series of N-ferrocene-substituted benzodihydrooxazoles were smoothly produced in moderate to excellent yields (up to >99% yield). The mechanism experiments showed that quinone esters performed as both substrate and oxidant. The salient features of this transformation include good functional group tolerance, broad substrate scope and mild conditions.

TBAI-Catalyzed S-H and N-H Insertion Reactions of α-Diazoesters with Thiophenols and Amines under Metal-Free Conditions.

Mild, convenient, and effective TBAI-catalyzed S-H and N-H insertion reactions of α-diazoesters with thiophenols and aromatic amines under metal-free conditions have been described, furnishing a straightforward and general platform for the synthesis of various thioethers and 2-amino-2-oxoacetates in moderate to excellent yields. Moreover, this strategy features simple operation, mild conditions, broad substrate scope, and easy scale-up.

Copper-Catalyzed Regio- and Stereoselective Sulfonylation of Alkynyl Imines with Sulfonyl Hydrazides: Access to (E)-ß-Sulfonyl Enones.

A copper-catalyzed sulfonylation of alkynyl imines with sulfonyl hydrazides has been developed, which exhibited excellent regio- and stereoselectivity and furnished a series of (E)-ß-sulfonyl enones in moderate to good yields. Mechanistic studies suggest that this strategy goes through a radical process.

A palladium-catalyzed sequential Heck coupling/C-C bond activation approach to oxindoles with all-carbon-quaternary centers.

Catalytic construction of oxindoles bearing all-carbon-quaternary centers attracts wide attention from the synthetic chemistry community. Herein, we report a palladium-catalyzed sequential Heck coupling/C-C bond activation of aryl halide-tethered alkenes with benzocyclobutenols affording a series of oxindole-derived compounds in good to excellent yields, as well as the preliminary enantioselectivity results.

Comparison of denosumab and oral bisphosphonates for the treatment of glucocorticoid-induced osteoporosis: a systematic review and meta-analysis.

BACKGROUND: Both denosumab and bisphosphonates have been demonstrated effective for glucocorticoid-induced osteoporosis. However, evidence-based medicine is still lacking to prove the clinical results between denosumab and bisphosphonates. This meta-analysis aims to compare the efficacy and safety between denosumab and oral bisphosphonates for the treatment of glucocorticoid-induced osteoporosis through evidence-based medicine. METHODS: MEDLINE, EMBASE, and the Cochrane library databases were searched up to June 2022 for randomized controlled trials that compared denosumab and oral bisphosphonates in the treatment of glucocorticoid-induced osteoporosis. The following outcomes were extracted for comparison: percentage change in bone mineral density from baseline at the lumbar spine, total hip, femoral neck, and ultra-distal radius; percentage change from baseline in serum concentration of bone turnover markers; and incidence of treatment-emergent adverse events. RESULTS: Four randomized controlled trials involving 714 patients were included. The pooled results showed that denosumab was superior to bisphosphonates in improving bone mineral density in lumbar spine (mean difference (MD) 1.70; 95% confidence interval (CI) 1.11-2.30; P < 0.001) and ultra-distal radius (MD 0.87; 95% CI 0.29-1.45; P = 0.003), and in suppressing C-terminal telopeptide of type 1 collagen (MD -34.83; 95% CI -67.37--2.28; P = 0.04) and procollagen type 1 N-terminal propeptide (MD -14.29; 95% CI -23.65- -4.94; P = 0.003) at 12 months. No significant differences were found in percentage change in total hip or femoral neck bone mineral density at 12 months, or in the incidence of treatment-emergent adverse events or osteoporosis-related fracture. CONCLUSIONS: Compared with bisphosphonates, denosumab is superior in improving bone mineral density in lumbar spine and ultra-distal radius for glucocorticoid-induced osteoporosis. Further studies are needed to prove the efficacy of denosumab.

PBN protects NP cells from AAPH-induced degenerative changes by inhibiting the ERK1/2 pathway.

Aim: Intervertebral disc (IVD) degeneration (IDD) is one of the main causes for spinal degenerative diseases, such as disk herniation, spinal canal stenosis, and spinal deformities. Growing evidence has highlighted the contribution of oxidative stress in pathogenesis of IDD, and antioxidant treatment is thus considered to be a promising therapeutic strategy for IDD. The aim of this study was to investigate whether N-tert-butyl-α-phenylnitrone (PBN), a free radical scavenger, could attenuate the pathological changes of IDD by alleviating oxidative stress.Materials and Methods: Nucleus pulposus (NP) cells were isolated from rabbit lumbar disks. MTT assay, real-time PCR and western blotting were employed to evaluate the effects of PBN on oxidative damages induced by 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) in NP cells.Results: AAPH induced oxidative stress and the subsequent degenerative changes in NP cells via the ERK/MAPK pathway. On the contrary, the oxidative stress induced by AAPH was significantly ameliorated by PBN. Moreover, PBN also attenuated AAPH-induced expression of matrix degradation proteases and apoptosis. PBN suppresses AAPH-induced activation of ERK/MAPK pathway, which may be the underlying mechanism for the protective effects of PBN.Conclusions: Our study for the first time identified a novel role and mechanism for PBN in protecting the IVD against oxidative stress, matrix catabolism and apoptosis, which may have implications for its further application in combating IVD degenerative diseases.Abbreviations: AAPH: 2,2'-azobis(2-methylpropanimidamidine) dihydrochloride; ADAMTS: a disintegrin and metalloproteinase with thrombospondin motifs; AF: annulus fibrosus; CEP: cartilage endplate; DCF: 2'7'-dichlorofluorescein; IDD: intervertebral disc degeneration; IVD: intervertebral disc; LPS: lipopolysaccharide; MMP: matrix metalloproteinase; MTT: methyl-thiazolyl-tetrazolium; NP: nucleus pulposus; PBN: N-tert-butyl-alfa-phenylnitrone; PGs: proteoglycans; ROS: reactive oxygen species; SDS: sodium dodecyl sulfate.

An organophotoredox-catalyzed C(sp2)-N cross coupling reaction of cyclic aldimines with cyclic aliphatic amines.

An organophotocatalyzed C(sp2)-H/N-H cross-dehydrogenative coupling of cyclic aldimines with aliphatic amines has been developed, which represents the first example of visible-light-induced C-H amination of N-sulfonylated imines. This methodology enables the streamline assembly of amine derivatives via radical mediated C-N bond formation. The current protocol features transition-metal-free, mild conditions, good functional group tolerance and good yields.

Clinical verification of vimentin/EpCAM immunolipid magnetic sorting system in monitoring CTCs in arterial and venous blood of advanced tumor.

BACKGROUND: Circulating tumor cells (CTCs) are the dominant factor leading to tumor metastasis. This study aims to investigate the effect of disparate sources of CTCs on the treatment and prognosis of patients with advanced tumors by analyzing the number and gene mutations change of CTCs in arterial and venous blood in patients with advanced tumors. RESULTS: A CTCs sorting system was constructed based on Vimentin-immunolipid magnetic balls (Vi-IMB) and EpCAM immunolipid magnetic balls (Ep-IMB). Results showed that the prepared Ep-IMB and Vi-IMB had lower cytotoxicity, better specificity and sensitivity. The number of arterial CTCs was higher than that of venous CTCs, with a statistically significant difference (P < 0.05). Moreover, the prognosis of the low positive group of total CTCs in arterial blood and venous blood was higher than that of the high positive group, with a statistical significance (P < 0.05). The genetic testing results showed that the targeted drug gene mutations in tissues, arterial CTCs and venous CTCs showed a complementary trend, indicating that there was heterogeneity among different tumor samples. CONCLUSIONS: CTCs in blood can be efficiently captured by the CTCs sorting system based on Vi-LMB/Ep-LMB, and CTCs detection in arterial blood can be utilized to more accurately evaluate the prognosis and predict postoperative progress. It is further confirmed that tumor samples from disparate sources are heterogeneous, providing a reference basis for gene mutation detection before clinical targeted drug treatment, and the detection of CTCs in arterial blood has more potential clinical application value. TRIAL REGISTRATION: The Ethics Committee of Putuo Hospital, PTEC-A-2019-18-1. Registered 24 September 2019.

Facile Synthesis of Sulfonyl Chlorides/Bromides from Sulfonyl Hydrazides.

A simple and rapid method for efficient synthesis of sulfonyl chlorides/bromides from sulfonyl hydrazide with NXS (X = Cl or Br) and late-stage conversion to several other functional groups was described. A variety of nucleophiles could be engaged in this transformation, thus permitting the synthesis of complex sulfonamides and sulfonates. In most cases, these reactions are highly selective, simple, and clean, affording products at excellent yields.