A new SO2 surrogate is reported that is cheap, bench‐stable, and can be accessed in just two steps from bulk chemicals. Essentially complete SO2 release is achieved in 5 minutes. Eight established ...sulfonylation reactions proceeded smoothly by ex situ formation of SO2 by utilizing a two‐chamber system in combination with the SO2 surrogate. Furthermore, we report the first direct aminosulfonylation between aryl iodides and amines. Broad functional group tolerance is demonstrated, and the method is applicable to pharmaceutically relevant substrates, including heterocyclic substrates.
A SO2 surrogate (SOgen) is reported, which is cheap, bench‐stable, and accessible in just two steps from bulk chemicals. SOgen releases SO2 in just a few minutes when heated in the presence of a styrene. The compatibility of this gas‐releasing method with eight previously reported sulfonylation reactions was demonstrated in a two‐chamber system. Direct aminosulfonylation between aryl iodides and amines is reported.
Total knee arthroplasty is a commonly performed safe procedure and typically executed in severe knee arthritis, but it also triggers ischemia‐reperfusion injury (IRI). More recently, microRNAs (miRs) ...have been reported to play a contributory role in IRI through the key signaling pathway. Hence, the current study aimed to investigate the effect and specific mechanism of microRNA‐23b (miR‐23b), murine double minute 4 (MDM4), and the p53 signaling pathway in IRI rat models. First, the IRI model was established, and the expression pattern of miR‐23b, MDM4, and the p53 signaling pathway‐related genes was characterized in cartilaginous tissues. Then, miR‐23b mimics or inhibitors were applied for the elevation or the depletion of the miR‐23b expression and siRNA‐MDM4 for the depletion of the MDM4 expression in the articular chondrocytes. By means of immunohistochemistry, quantitative real‐time polymerase chain reaction, and Western blot analysis, IRI rats exhibited increased miR‐23b expression, activated p53 signaling pathway, and decreased MDM4 expression. MDM4 was verified as a target gene of miR‐23b through. Downregulated miR‐23b increased the expression of MDM4, AKT, and Bcl‐2, but decreased the expression of p53, p21, and Bax. In addition, a series of cell experiments demonstrated that downregulated miR‐23b promoted articular chondrocyte proliferation and cell cycle entry, but inhibited articular chondrocyte apoptosis. The absence of the effects of miR‐23b was observed after MDM4 knocked down. Our results indicate that silencing miR‐23b could act to attenuate IRI and reduce the apoptosis of articular chondrocytes through inactivation of the p53 signaling pathway by upregulating MDM4, which provide basic therapeutic considerations for a novel target against IRI.
Our results indicate that silencing microRNA‐23b could act to attenuate ischemia‐reperfusion injury (IRI) and reduce the apoptosis of articular chondrocytes through inactivation of the p53 signaling pathway by upregulating murine double minute 4, which provide basic therapeutic considerations for a novel target against IRI.
Comprehensive Summary
Carbonyl compounds have attracted considerable attention due to their extensive applications in drug discovery. Furthermore, they are important synthetic intermediates for the ...construction of carbon‐carbon and carbon‐heteroatom bonds. Transition‐metal‐catalyzed carbonylation via the insertion of CO is one of the most efficient and straightforward strategies to access carbonyl compounds. However, most of the transition‐metal‐catalyzed carbonylative reactions require expensive and toxic noble‐metal catalysts. Therefore, there is a growing demand for the exploration of nickel‐catalyzed carbonylative reactions via the insertion of CO due to the earth abundance and low cost of nickel. Compared with the well‐established palladium‐catalyzed carbonylative reactions, nickel‐catalyzed analogous transformations have been relatively underdeveloped. This is primarily because CO strongly binds to nickel, often resulting in catalyst poisoning. In recent years, some research groups have focused on using CO surrogates or NN2 pincer nickel catalyst to circumvent the formation of Ni(CO)4. Nickel‐catalyzed carbonylation has been applied in the construction of carbonyl‐containing compounds, such as ketones, carboxylic acids, thioesters, acyl chloride and carboxamides.
In this review, we provide a comprehensive overview of the advancements in the nickel catalyzed carbonylative reactions from 2017 to March 2023. The nickel catalyzed carbonylative reactions reported during this period have been categorized into four groups based on the source of CO: free CO gas, metal carbonyl complexes, organic CO surrogates, and ex‐situ generated CO from COgen. Additionally, we will also discuss the potential for further development in this field as well as the associated challenges.
Among all metathesis reactions known to date in organic chemistry, the metathesis of multiple bonds such as alkenes and alkynes has evolved into one of the most powerful methods to construct ...molecular complexity. In contrast, metathesis reactions involving single bonds are scarce and far less developed, particularly in the context of synthetically valuable ring‐closing reactions. Herein, we report an iron‐catalyzed ring‐closing metathesis of aliphatic ethers for the synthesis of substituted tetrahydropyrans and tetrahydrofurans, as well as morpholines and polycyclic ethers. This transformation is enabled by a simple iron catalyst and likely proceeds via cyclic oxonium intermediates.
Iron‐forged rings: An iron‐catalyzed ring‐closing metathesis of aliphatic ethers generates substituted tetrahydropyrans and tetrahydrofurans, as well as morpholines and polycyclic ethers. This transformation is enabled by a simple iron catalyst and likely proceeds via cyclic oxonium intermediates.
In locoregionally advanced nasopharyngeal carcinoma (LANPC) patients, variance of tumor response to induction chemotherapy (ICT) was observed. We developed and validated a novel imaging biomarker to ...predict which patients will benefit most from additional ICT compared with chemoradiotherapy (CCRT) alone.
All patients, including retrospective training (n = 254) and prospective randomized controlled validation cohorts (a substudy of NCT01245959, n = 248), received ICT+CCRT or CCRT alone. Primary endpoint was failure-free survival (FFS). From the multi-parameter magnetic resonance images of the primary tumor at baseline, 819 quantitative 2D imaging features were extracted. Selected key features (according to their interaction effect between the two treatments) were combined into an Induction Chemotherapy Outcome Score (ICTOS) with a multivariable Cox proportional hazards model using modified covariate method. Kaplan-Meier curves and significance test for treatment interaction were used to evaluate ICTOS, in both cohorts.
Three imaging features were selected and combined into ICTOS to predict treatment outcome for additional ICT. In the matched training cohort, patients with a high ICTOS had higher 3-year and 5-year FFS in ICT+CCRT than CCRT subgroup (69.3% vs. 45.6% for 3-year FFS, and 64.0% vs. 36.5% for 5-year FFS; HR = 0.43, 95% CI = 0.25-0.74, p = 0.002), whereas patients with a low ICTOS had no significant difference in FFS between the subgroups (p = 0.063), with a significant treatment interaction (p
< 0.001). This trend was also found in the validation cohort with high (n = 73, ICT+CCRT 89.7% and 89.7% vs. CCRT 61.8% and 52.8% at 3-year and 5-year; HR = 0.17, 95% CI = 0.06-0.51, p < 0.001) and low ICTOS (n = 175, p = 0.31), with a significant treatment interaction (p
= 0.019). Compared with 12.5% and 16.6% absolute benefit in the validation cohort (3-year FFS from 69.9 to 82.4% and 5-year FFS from 63.4 to 80.0% from additional ICT), high ICTOS group in this cohort had 27.9% and 36.9% absolute benefit. Furthermore, no significant survival improvement was found from additional ICT in both groups after stratifying low ICTOS patients into low-risk and high-risks groups, by clinical risk factors.
An imaging biomarker, ICTOS, as proposed, identified patients who were more likely to gain additional survival benefit from ICT+CCRT (high ICTOS), which could influence clinical decisions, such as the indication for ICT treatment.
ClinicalTrials.gov , NCT01245959 . Registered 23 November 2010.
Ten new (
-
) and 26 known (
-
) compounds were isolated from
MCCC 3A00225, a deep sea-derived fungus. The structures of the new compounds were determined by detailed analysis of the NMR and HRESIMS ...spectroscopic data. The absolute configurations were established by X-ray crystallography, Marfey's method, and the ICD method. All isolates were tested for in vitro anti-food allergic bioactivities in immunoglobulin (Ig) E-mediated rat basophilic leukemia (RBL)-2H3 cells. Compound
significantly decreased the degranulation release with an IC
value of 60.3 μM, compared to that of 91.6 μM of the positive control, loratadine.
A palladium‐catalyzed domino cyclization/direct aminosulfonylation of aryl iodides with amines via the insertion of SO2 (from SOgen) was presented. This method could produce a series of ...oxindole‐based sulfonamides in moderate‐to‐good yields. A scale‐up reaction and two synthetic applications demonstrated the robustness and practicality of this transformation.
Atherosclerosis (AS) is a chronic inflammatory disease of the vascular wall with multiple causes. AS is the primary pathological basis of cardiovascular disease and stroke. Moreover, carotid plaque ...rupture and thrombus formation are the main causes of ischemic stroke. Therefore, understanding the formation of carotid plaques may help improve the prediction and prevention of cardiovascular and cerebrovascular events. Endothelial cell dysfunction results in re‑endothelialization and angiogenesis in atherosclerotic plaques, thus promoting plaque destabilization. The aim of the present study was to evaluate the effect of circular RNA (circRNA) molecules in serum exosomes (serum‑Exos) from patients with stable plaque atherosclerosis (SA) and unstable/vulnerable plaque atherosclerosis (UA). Specifically, the effect of circRNA on human umbilical vein endothelial cell (HUVEC) behavior and the mechanisms underlying plaque destabilization in AS were evaluated. Serum‑Exos were isolated, then identified using transmission electron microscopy, nanoparticle tracking analysis and western blotting. The serum‑Exo‑circRNA expression profile of patients with SA or UA was investigated using a circRNA array. The relationship between circRNA‑006896 in serum‑Exos and biochemical parameters of patients with SA and UA were analyzed using Spearman's correlation. In addition, HUVECs were incubated with serum‑Exos for
functional assays. The present study demonstrated that circRNAs expression profiles in SA and UA serum‑Exos were significantly different, indicating a potential role for circRNAs in carotid plaque destabilization. The expression of circRNA‑0006896 was positively correlated with triglyceride, low‑density lipoprotein cholesterol (LDL‑C) and C‑reactive protein levels, and negatively correlated with albumin levels in patients with UA. However, circRNA‑0006896 expression was positively correlated with LDL‑C in patients with SA. Using bioinformatic analysis, a competing endogenous RNA (ceRNA) network was selected to study the regulatory roles of circRNA‑0006896 in serum‑Exos. Additionally, in HUVECs treated with serum‑Exos derived from patients with UA, the expression of circRNA‑0006896 in HUVECs was upregulated. This was accompanied by decreased expression of microRNA‑1264 and SOCS3, increased levels of DNMT1 and phosphorylated STAT3. HUVEC proliferation and migration were significantly increased in the UA group, compared with the mock and SA groups. This finding indicates that the circRNA‑0006896‑miR-1264‑DNMT1 axis plays an important role in carotid plaque destabilization by regulating the behavior of endothelial cells. Moreover, it suggests that circRNA‑0006896 may represent a therapeutic target for controlling JNK/STAT3 signaling in HUVECs. Thus, this study may provide insight on potential interventions against vulnerable plaque formation in patients with AS.
Summary
In this study, a hybrid system was prepared by mixing rice starch (RS) with different mass fractions (0%–10% dry weight) of soy protein isolate (SPI) to investigate its retrogradation ...characteristics during storage. The results showed that the addition of SPI led to an increase in pasting temperature and a decrease in setback (SB) and aging rate (P < 0.05). When the level of SPI was increased to 10%, the pasting temperature reached a peak of 75.28°C, resulting in a decrease of 16.52% in regrowth rate and 51.61% in aging rate. The analysis of hardness and secondary structure indicated that the inclusion of SPI resulted in a less robust starch gel structure in comparison to RS, leading to a decrease in gel hardness and the short‐range ordered structure of starch. The pore structure of the starch gel was observed to be smaller and more uniform following the addition of SPI. The presence of SPI hindered the recrystallisation of starch granules, consequently leading to a delay in starch retrogradation. The results of this study have validated the positive effect of incorporating SPI on the anti‐aging properties of starch during storage. This serves as a foundational basis for enhancing the processing attributes of RS and the overall quality of starchy food products.
Impact of soybean protein isolate on rice starch retrogradation.
PDF
