Synthesis and antitumor activity of three novel ginsenoside M1 derivatives with 3'-ester modifications.

Ginsenoside M1 (M1) was considered to be the main antitumor component of ginsenoside metabolites in the body. In order to enhance its potency on antitumor effect, three novel M1 3'-ester derivatives (1c, 2c, 3c) were synthesized and evaluated. The yield of these derivatives was between 41% and 69%. Compared with M1, 2c and 3c can improve the efficacy of the inhibition on breast cancer MCF-7 and MDA-MB-231 cells, especially for MCF-7 (fold: 0.7-4.2, p < 0.0001). Further study suggested that 2c and 3c may cause cell autophagy and promote apoptosis in MCF-7 cells. The results indicated the 3'-ester modified M1 derivatives 2c and 3c possess higher abilities of inhibition growth towards triple-positive breast cancer and provided a new source for synthesis of potential anti-breast cancer drugs.

Copper-Catalyzed Dimerization/Cyclization of Itaconates.

A copper-catalyzed domino reaction between itaconate esters and diethyl zinc (or silane) is developed, affording itaconate dimerization products, multi-ester-substituted cyclopentanones, in moderate to high yields.

Copper-catalyzed cascade reactions of α,ß-unsaturated esters with keto esters.

A copper-catalyzed cascade reaction of α,ß-unsaturated esters with keto esters is reported. It features a copper-catalyzed reductive aldolization followed by a lactonization. This method provides a facile approach to prepare γ-carboxymethyl-γ-lactones and δ-carboxymethyl-δ-lactones under mild reaction conditions.

Analysis of the effects of early screening combined with blood lactate on the severity of patients with sepsis.

This work aimed to investigate the adoption value of blood lactic acid (BLA) combined with the National Early Warning Score (NEWS) in the early screening of sepsis patients and assessing their severity. The data and materials utilized in this work were obtained from the electronic medical record system of 537 anonymized sepsis patients who received emergency rescue in the emergency rescue area of Liuzhou People's Hospital, Guangxi, from July 1, 2020, to December 26, 2020. Based on the 28-day outcomes of sepsis patients, the medical records were rolled into Group S (407 survival cases) and Group D (130 dead cases). Basic information such as the mode of hospital admission, initial management, use of emergency ventilator within 24 h of admission, NEWS score, arterial oxygen pressure/alveolar oxygen pressure ratio (PaO2/PAO2), alveolar-arterial oxygen difference (A-aDO2), serum creatinine (SCr), blood urea nitrogen (BUN), oxygenation index (OI), Glasgow Coma Scale (GCS), D-dimer, use of vasoactive drugs within 24 h of admission, C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), N-terminal pro-B-type natriuretic peptide (NT-proBNP), quick Sequential Organ Failure Assessment (qSOFA) score, SOFA score, BLA level, NEWS with lactate (NEWS-L) score, SOFA score including lactate level (SOFA-L) score, Intensive Care Unit (ICU) length of stay, total hospital stay, ICU stay/total hospital stay, and septic shock condition were compared between groups. Logistic regression analysis was performed to assess the impact of various predictive factors on prognosis and to plot the receiver operating characteristic (ROC) curve. The results suggested marked differences between Group S and Group D in terms of mean age (t = -5.620; OR = -9.96, 95 % CI: -13.44∼-6.47; P < 0.001). Group S showed drastic differences in terms of mode of hospital admission (χ2 = 9.618, P < 0.01), method of initial management (χ2 = 51.766, P < 0.001), use of emergency ventilator within 24 h of admission (χ2 = 98.564, P < 0.001), incidence of septic shock (χ2 = 77.545, P < 0.001), use of vasoactive drugs within 24 h of admission (χ2 = 102.453, P < 0.001), heart rate (t = -4.063, P < 0.001), respiratory rate (t = -4.758, P < 0.001), oxygenation status (χ2 = 20.547, P < 0.001), NEWS score (t = -6.120, P < 0.001), PaO2/PAO2 ratio (t = 2.625, P < 0.01), A-aDO2 value (Z = -3.581, P < 0.001), OI value (Z = -3.106, P < 0.01), PLT value (Z = -2.305, P < 0.05), SCr value (Z = -3.510, P < 0.001), BUN value (Z = -3.170, P < 0.01), D-dimer (Z = -4.621, P < 0.001), CRP level (Z = -4.057, P < 0.001), PCT value (Z = -2.783, P < 0.01), IL-6 level (Z = -2.904, P < 0.001), length of hospital stay (Z = -4.138, P < 0.001), total hospital stay (Z = -8.488, P < 0.001), CCU/total hospital stay (Z = -9.118, P < 0.001), NEWS score (t = -6.120, P < 0.001), SOFA score (t = -6.961, P < 0.001), SOFA-L score (Z = -4.609, P < 0.001), NEWS-L score (Z = -5.845, P < 0.001), BLA level (Z = -6.557, P < 0.001), and GCS score (Z = 6.909, P < 0.001) when compared to Group D. The use of ventilators, septic shock, PCT, NEWS score, GCS score, SOFA score, SOFA-L score, NEWS-L score, and BLA level were identified as independent risk factors for predicting the prognosis of sepsis patients (P < 0.001). The areas under ROC curve (AUC) of blood lactic acid, PCT, NEWS, NEWS-L, GCS, SOFA, and SOFA-L were 0.695, 0.665, 0.692, 0.698, 0.477, 0.700, and 0.653, respectively. These findings indicate that the combination of BLA with NEWS (NEWS-L) score and SOFA score has certain advantages in assessing the prognosis of sepsis.

Enhancing Mechanical Properties of Graphene/Aluminum Nanocomposites via Microstructure Design Using Molecular Dynamics Simulations.

This study explores the mechanical properties of graphene/aluminum (Gr/Al) nanocomposites through nanoindentation testing performed via molecular dynamics simulations in a large-scale atomic/molecular massively parallel simulator (LAMMPS). The simulation model was initially subjected to energy minimization at 300 K, followed by relaxation for 50 ps under the NPT ensemble, wherein the number of atoms (N), simulation temperature (T), and pressure (P) were conserved. After the model was fully relaxed, loading and unloading simulations were performed. This study focused on the effects of the Gr arrangement with a brick-and-mortar structure and incorporation of high-entropy alloy (HEA) coatings on mechanical properties. The findings revealed that Gr sheets (GSs) significantly impeded dislocation propagation, preventing the dislocation network from penetrating the Gr layer within the plastic zone. However, interactions between dislocations and GSs in the Gr/Al nanocomposites resulted in reduced hardness compared with that of pure aluminum. After modifying the arrangement of GSs and introducing HEA (FeNiCrCoAl) coatings, the elastic modulus and hardness of the Gr/Al nanocomposites were 83 and 9.5 GPa, respectively, representing increases of 21.5% and 17.3% compared with those of pure aluminum. This study demonstrates that vertically oriented GSs in combination with HEA coatings at a mass fraction of 3.4% significantly enhance the mechanical properties of the Gr/Al nanocomposites.

Synthesis of esters of ginsenoside metabolite M1 and their cytotoxicity on MGC80-3 cells.

Monoesters of ginsenoside metabolite M1 at the 3-OH, 4-OH and 6-OH positions of the glucose moiety at M1 were synthesized via the reaction of M1 with acyl chloride, or acid-N,N'-diisopropylcarbodiimide in the presence of DMAP. Their structures were fully characterized by spectral methods. The cytotoxicity of these compounds against then MGC80-3 human gastric cancer cell line was also assessed. High inhibitory effects were found at a concentration of 100 µg/mL.

Methylprednisolone or dexamethasone? How should we choose to respond to COVID-19?: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Methylprednisolone (MP) and dexamethasone (DXM) are commonly prescribed hormone drugs for treating coronavirus pandemic disease 2019 (COVID-19) patients, but conflicting results from previous studies and meta-analyses on their efficacy and safety necessitate further investigation. Therefore, in this study, we conducted a systematic review and meta-analysis of randomized controlled trials to enhance the level of evidence and compare the efficacy and safety of MP and DXM in COVID-19 patients. METHODS: We conducted a comprehensive search of PubMed, Web of Science, Embase, and Cochrane Library databases to retrieve randomized clinical trials. Our primary outcome measure was all-cause mortality, with secondary outcomes including admission to the intensive care unit, length of hospital stay, mechanical ventilation, and adverse events. RESULTS: This study analyzed six randomized controlled trials involving 1403 patients (MP group: 704; DXM group: 699). The results of the analysis showed no significant differences in mortality rates, admission to intensive care units, hospitalization time, mechanical ventilation, or adverse events between the MP and DXM groups (P > .05). However, a significant difference was observed in the incidence of hyperglycemia between these 2 groups (RR = 1.78, 95% CI [1.09, 2.89], P = .02, I2 = 78%). CONCLUSION: The results of this meta-analysis showed that there was no difference in mortality, ICU admission rate, hospital stay, mechanical ventilation, or adverse events between MP and DXM in the treatment of COVID-19. The incidence of hyperglycemia with methylprednisolone was higher than that with dexamethasone.

Suzuki-Miyaura reactions catalyzed by C2-symmetric Pd-multi-dentate N-heterocyclic carbene complexes.

Suzuki-Miyaura coupling reactions are promoted by Pd complexes ligated with C2-symmetric multi-dentate N-heterocyclic carbenes derived in situ from Pd(OAc)2 and imidazolium salts. Good to excellent yields were obtained for aryl bromides as substrates. Turnover numbers of up to 105 could be achieved with 5 × 10⁻4 mol% of Pd(OAc)2/1 × 10⁻³ mol% NHC precatalyst in 24 h.

Aerosol Inhalation of Heat-Killed Clostridium butyricum CGMCC0313-1 Alleviates Allergic Airway Inflammation in Mice.

Epidemiological studies have shown that exposure to beneficial microorganisms can reduce the risk of asthma, but the clinical use of live probiotics is controversial due to the risk of infection. As heat-killed probiotics can also exhibit immunomodulatory activity, this study is aimed at investigating whether heat-killed Clostridium butyricum (HKCB) CGMCC0313-1 could reduce allergic airway inflammation in an ovalbumin-induced mouse model. Mice received aerosol inhalation of HKCB, oral administration of HKCB, or oral administration of live Clostridium butyricum (CB) during sensitization. Bronchoalveolar lavage fluid cell number, histology, and levels of the cytokines interferon-gamma and IL-4, the autophagy-related proteins LC3B, Beclin1, and p62, and members of the nuclear factor kappa B (NF-κB)/NLRP3 inflammasome signaling pathway were examined. Our results demonstrated that aerosol inhalation of HKCB, oral HKCB administration, and oral live CB administration alleviated allergic airway inflammation and mucus secretion in allergic mice. Aerosol inhalation of HKCB was the most effective method; it restored the Th1/Th2 balance, ameliorated autophagy, and inhibited the NF-κB/NLRP3 inflammasome signaling pathway in the lungs of allergic mice. Thus, aerosol inhalation of HKCB could be a promising strategy for the prevention or treatment of asthma.

Hydrophilic/Hydrophobic Heterogeneity Anti-Biofouling Hydrogels with Well-Regulated Rehydration.

Hydrogels, as a representative of soft and biocompatible materials, have been widely used in biosensors, biomedical devices, soft robotics, and the marine industry. However, the ir-recoverability of hydrogels after dehydration, which causes the loss of original mechanical, optical, and wetting properties, has severely restricted their practical applications. At present, this critical challenge of maintaining hydrogels' accurate character has attracted less attention. To address this, here we report a hydrogel based on synergistic effects to achieve both well-regulated rehydration and deswelling properties. The hydrogel after dehydration can quickly restore its original state both on the macro- and microscale. In addition, the hydrogel has excellent mechanical stability after several dehydration-rehydration cycles. All of these properties offer a possibility of water condition endurance and increase the service life. The robust property is attributed to the hydrophilic-hydrophobic and ionic interactions induced by the synergy of hydrophilic/oleophilic heteronetworks. Moreover, zwitterionic segments as hydrophilic network play a vital role in fabricating anti-biofouling hydrogels. The durable and reusable hydrogel may have promising applications for biomedical materials, flexible devices, and the marine industry.

Design of hierarchical comb hydrophilic polymer brush (HCHPB) surfaces inspired by fish mucus for anti-biofouling.

Anti-biofouling surfaces are of high importance owing to their crucial roles in biosensors and biomedical devices, especially in the marine industry. However, traditional anti-biofouling surfaces based on either the release of biocidal compounds or surface peeling will contaminate the environment. The outstanding performances of natural anti-biofouling surfaces motivate the development of new bioinspired antifouling surfaces. Herein, a universal strategy inspired by the special performance of fish skin mucus is proposed for rationally designing anti-biofouling surfaces using grafted hierarchical comb hydrophilic polymer brushes (HCHPBs) on plastics and elastomers. The results show that the plastic substrate surface grafted PAA (polyacrylic acid)-g-PEG (polyethylene glycol) (MW 2000, 6000, and 11 000 Da) exhibits excellent hydrophilic and underwater oleophobic properties, and also shows good performance in terms of lubricity and drag reduction in water, which can be attributed to the HCHPB and the nanostructure on plastic surfaces. In addition, the modified substrate shows superior and long-lasting anti-biofouling properties to resist the adhesion of algae compared to the initial substrate. This comprehensive investigation is of great importance to understand the physicochemical properties of hierarchical comb hydrophilic polymer brushes and the mechanism against the adhesion of marine microorganisms.

Experimental Investigation of Compression Properties of Composites with Printed Braiding Structure.

A kind of composite was designed and additive manufacturing (AM) technology was utilized in the braiding structure fabrication. The printed polylactic acid (PLA) braiding structures were integrated with two types of resins (Epon 828 resin and urethane dimethacrylate/triethylene glycol dimethacrylate (UDMA/TEDGMA) resin) used as the matrix to make composite specimens. The compression test of the composite specimens showed that the printed PLA braiding structures had the effect of varying the compression properties of pure resins: it decreased the compression properties of Epon 828 resin, but increased those of UDMA/TEGDMA resin. Observing scanning electron microscope (SEM) images, it was noted that the decreasing and increasing in the compression properties of the specimens were related to the bonding compactness between the printed braiding structure and resins. Our results may suggest a new methods for the fast manufacturing of AM-based composites, further research directions, and potential applications of this kind of composites.

Rearrangements of α-Diazo-ß-hydroxyketones for the Synthesis of Bicyclo[m.n.1]alkanones.

Rhodium-catalyzed decomposition of fused bicyclic α-diazo-ß-hydroxyketones results in good yields of bridged bicyclo[m.n.1]ketones via a rearrangement pathway.

A novel stereoselective one-pot conversion of alcohols into alkyl halides mediated by N,N'-diisopropylcarbodiimide.

Alcohols can be converted in high yields to the corresponding alkyl halides in a one-pot procedure via the corresponding O-alkylisourea; very short reaction times are possible when microwave irradiation is used.

Crystalline amidocerium(IV) oxides and a side-on bridging dioxygen complex.

Complexes [Ce(NR(2))(3)] (1) or [Ce(NR''(2))(3)] (2) were cerium(III) precursors to the X-ray characterised crystalline oligomeric oxygen-containing amidocerium(IV) compounds [{Ce(NR(2))(2)(mu-O)}(n)] (3, n = 2; 4, n = 3), [{Ce(NR''(2))(2)(mu-O)}(4)] (5), [{(R(2)N)(3)Ce}(2)(mu-[upper bond 1 start]OMOM[upper bond 1 end])] (6, M = Na; 7, M = K), [{(R(2)N)(3)CeOCe(NR(2))(2)}(2)(mu-[upper bond 1 start]OKOK[upper bond 1 end])] (8), and [{Ce(NR(2))(3)}(2)(mu-eta(2):eta(2)-O(2))].2C(n)H(2n+2) (9, n = 6; 9', n = 5) [R = SiMe(3), NR''(2) = TMP = [upper bond 1 start]NC(Me)(2)(CH(2))(3)C[upper bond 1 end]Me(2)]. Each was isolated in low, or for 5 very low, yield. Except for 4, the oxidising agent was O(2) at -27 degrees C in hexane (3, 6, 7, 8, 9), pentane (9'), or toluene (5), and a co-reagent for the alkali metal bis(trimethylsilyl)amido(oxy)cerate(iv)s was NaNR(2) (8) or KNR(2) (7, 8). From 1 and an equivalent portion of 2,6-(t)Bu(2)-benzoquinone after 5 weeks in pentane there was obtained the bis(amido)cyclotricer(IV)oxane 4. The NMR spectral solution chemical shifts for NR(2) groups of 3, 4, and 6-9 were consistent with each sample being diamagnetic and hence a Ce(IV) species. A transient amidocerium(IV) superoxide Ce(NR(2))(3)(eta(2)-O(2)) (J), or its TMP analogue, is considered to be the common first-formed intermediate in each case, while 4 is believed to have arisen from the adventitious hydrolysis of [{Ce(NR(2))(3)O}(2)((t)Bu(2)C(6)H(2)-1,4)].

Nicotinamide overload may play a role in the development of type 2 diabetes.

AIM: To investigate whether nicotinamide overload plays a role in type 2 diabetes. METHODS: Nicotinamide metabolic patterns of 14 diabetic and 14 non-diabetic subjects were compared using HPLC. Cumulative effects of nicotinamide and N(1)-methylnicotinamide on glucose metabolism, plasma H(2)O(2) levels and tissue nicotinamide adenine dinucleotide (NAD) contents of adult Sprague-Dawley rats were observed. The role of human sweat glands and rat skin in nicotinamide metabolism was investigated using sauna and burn injury, respectively. RESULTS: Diabetic subjects had significantly higher plasma N(1)-methylnicotinamide levels 5 h after a 100-mg nicotinamide load than the non-diabetic subjects (0.89 +/- 0.13 micromol/L vs 0.6 +/- 0.13 micromol/L, P < 0.001). Cumulative doses of nicotinamide (2 g/kg) significantly increased rat plasma N(1)-methylnicotinamide concentrations associated with severe insulin resistance, which was mimicked by N(1)-methylnicotinamide. Moreover, cumulative exposure to N(1)-methylnicotinamide (2 g/kg) markedly reduced rat muscle and liver NAD contents and erythrocyte NAD/NADH ratio, and increased plasma H(2)O(2) levels. Decrease in NAD/NADH ratio and increase in H(2)O(2) generation were also observed in human erythrocytes after exposure to N(1)-methylnicotinamide in vitro. Sweating eliminated excessive nicotinamide (5.3-fold increase in sweat nicotinamide concentration 1 h after a 100-mg nicotinamide load). Skin damage or aldehyde oxidase inhibition with tamoxifen or olanzapine, both being notorious for impairing glucose tolerance, delayed N(1)-methylnicotinamide clearance. CONCLUSION: These findings suggest that nicotinamide overload, which induced an increase in plasma N(1)-methylnicotinamide, associated with oxidative stress and insulin resistance, plays a role in type 2 diabetes.

Cerium(III) dialkyl dithiocarbamates from [Ce[N(SiMe3)2]3] and tetraalkylthiuram disulfides, and [Ce(kappa2-S2CNEt2)4] from the Ce(III) precursor; Tb(III) and Nd(III) analogues.

The synthesis and characterisation of the first neutral cerium dialkyl dithiocarbamate complexes, using a novel oxidative displacement of the amido ligands of [Ce[N(SiMe3)2]3] by tetraalkylthiuram disulfides [R2NC(S)S]2(R = Me, Et) in thf solution, are reported. In the absence of other donors, the complexes [Ce(kappa2-S2CNMe2)3(thf)2] and Ce(kappa2-S2CNEt2)3) 3 were obtained. The addition of a polypyridyl ligand allowed easy access to a range of complexes of general formula [Ce(kappa2-S2CNR2)3(L[intersection]L)][R = Me and L([intersection])L = 2,2'-bipy (4), or 4,7-diphenyl-1,10-phenanthroline (6); or R = Et and L[intersection]L = 2,2'-bipy (5)]. Brief exposure of the Ce(III) dithiocarbamate to oxygen gas afforded in high yield the diamagnetic, crystalline Ce(IV) dithiocarbamate [Ce(kappa2-S2CNEt2)4)] 7. The neodymium (8) and terbium (10) complexes, isoleptic with 2, were prepared from the appropriate 4f metal (Ln) bis(trimethylsilyl)amide [Ln[pN(SiMe3)2]3][Ln = Nd or Tb (9)] and [Me2NC(S)S]2. The structures of the crystalline complexes, 2, 4, 6, 7, 9 and 10 have been determined by X-ray crystallography. Some evidence has been obtained for the formation of the cerium(IV) complex Ce[N(SiMe3)2]2(kappa2-S2CNMe2)2. The cerium(IV) complex 7 has the metal coordinated to eight sulfur atoms of four planar chelating S2CNC2 moities and its geometry is intermediate between dodecahedral and square prismatic; the mean Ce-S bond length of 2.803 A in 7 compares with the 2.950 A in the Ce(III) complex 2.

Synthetic and structural experiments on yttrium, cerium and magnesium trimethylsilylmethyls and their reaction products with nitriles; with a note on two cerium beta-diketiminates.

The yttrium, cerium and magnesium bis(trimethylsilyl)methyls [Ln[CH(SiMe3)2]3][Ln = Y (1), Ce (2)], and the known compound Mg[[CH(SiMe3)2]2 (C) and [Mg(mu-Br)[CH(SiMe3)2](OEt2)]2 (D) formed the crystalline nitrile adducts [1(NCBut)2] (5), [2(NCPh)] (6), [C(NCR)2][R = But (8), Ph (9), C6H3Me2-2,6 (10)] and [Mg(mu-Br)[CH(SiMe3)2](NCR)]2 [R = But (11), Ph (12), C6H3Me2-2,6 (13)], rather than beta-diketiminato-metal insertion products. The beta-diketiminato-cerium complex [Ce[(N(SiMe3)C(C6H4But-4))2CH][N(SiMe3)2]2] (16) was obtained from [Ce[N(SiMe3)2]3] and the beta-diketimine H[[N(SiMe3)C(C6H4But-4)]2CH]]. The cerium alkyl 2 and [Ln[CH(SiMe3)(SiMe2OMe)]3][Ln = Y (3), Ce (4)] were obtained from the appropriate lithium alkyl precursor and [Ce(OC6H2But2-2,6-Me-4)3] or LnCl3, respectively. Heating complex 3 with benzonitrile in toluene afforded 2,2-dimethyl-4,6-diphenyl-5-trimethylsilyl-1,3-diaza-2-silahexa-1,3-diene (7), a member of a new class of heterocycles. The X-ray structures of the crystalline compounds, D, [Mg[CH(SiMe3)2]2(OEt2)2], the known [Ce(Cl)[(N(SiMe3)C(Ph))2CH]2] (E) and 16 are reported. The cerium alkyl (like 1) has one close Ce...C contact for each ligand, attributed to a gamma-C-Ce agostic interaction. The Ln alkyls and have a trigonal prismatic arrangement of the chelating ligands (each of the same chirality at Calpha) around the metal. In an arene solution at 313 K exists as two isomers, as evident from detailed NMR spectroscopic experiments.