Chemo-, Regio- and Stereoselective Preparation of (Z)-2-Butene-1,4-Diol Monoesters via Pd-Catalyzed Decarboxylative Acyloxylation.

(Z)-alkenes are useful synthons but thermodynamically less stable than their (E)-isomers and typically more difficult to prepare. The synthesis of 1,4-hetero-bifunctionalized (Z)-alkenes is particularly challenging due to the inherent regio- and stereoselectivity issues. Herein we demonstrate a general, chemoselective and direct synthesis of (Z)-2-butene-1,4-diol monoesters. The protocol operates within a Pd-catalyzed decarboxylative acyloxylation regime involving vinyl ethylene carbonates (VECs) and various carboxylic acids as the reaction partners under mild and operationally attractive conditions. The newly developed process allows access to a structurally diverse pool of (Z)-2-butene-1,4-diol monoesters in good yields and with excellent regio- and stereoselectivity. Various synthetic transformations of the obtained (Z)-2-butene-1,4-diol monoesters demonstrate how these synthons are of great use to rapidly diversify the portfolio of these formal desymmetrized (Z)-alkenes.

PBA-MoS2 nanoboxes with enhanced peroxidase activity for constructing a colorimetric sensor array for reducing substances containing the catechol structure.

Some nanoperoxidase-based colorimetric sensors have been used to detect only one molecule at a time. Thus, the simultaneous detection of various molecules coexisting in the same system is a great challenge. In this work, an excellent nanoperoxidase, nickel cobalt Prussian blue analogue-MoS2 nanoboxes (PBA-MoS2), have been successfully prepared by the hydrothermal method and used to construct a colorimetric sensing array to determine a series of reductive substances containing the catechol structure (such as catechol, epinephrine hydrochloride, procyanidin, caffeic acid and dopamine hydrochloride). The excellent peroxidase-like activity of PBA-MoS2 is verified by the chromogenic reaction of 3,3,5,5-tetramethylbenzidine (TMB) in the presence of H2O2 in 2 min. The catalytic mechanism of PBA-MoS2 is attributed to generated reactive species including holes (h+) and superoxide radicals (˙O2-) in the process of catalysis. The fast economic H2O2 colorimetric sensing array has been constructed based on the PBA-MoS2 nanoperoxidase. Due to the presence of different reducing substances, the catalytic oxidation of TMB can be restricted to different extents, accompanied by blue colour changes to varying degrees. Therefore, on combining PBA-MoS2 nanoperoxidase with H2O2 and TMB, five reductive substances can be quantitatively distinguished by linear discriminant analysis (LDA) at the 2 mM level.

Enhancement Strategy of Photoelectrocatalytic Activity of Cobalt-Copper Layer Double Hydroxide toward Methanol Oxidation: Cerium Doping and Modification with Porphyrin.

Designing durable, high-active, and low-cost noble-metal-free photoelectrocatalysts for methanol electrooxidation is highly demanded but remains a challenge. Herein, the photoelectrocatalytic activity of cobalt-copper layer double hydroxide (CoCu-LDH) for methanol oxidation reaction (MOR) in the alkaline media under light was remarkably enhanced by cerium (Ce) doping and further by 5,10,15,20-tetrakis(4-carboxylphenyl)porphyrin (TCPP) modification. TCPP/Ce-CoCu-LDH exhibits a remarkable mass activity of 1788.2 mA mg-1 in 1 mol L-1 KOH with 1 mol L-1 methanol under light, which is 2.3 and 1.8 times higher than that of CoCu-LDH (782.2 mA mg-1) and Ce-CoCu-LDH (987.4 mA mg-1). The UV-vis diffuse reflectance spectra and photoluminescence emission spectra reveal that TCPP/Ce-CoCu-LDH can effectively utilize the visible light and inhibit the electron-hole pairs' recombination because of the introduction of porphyrin. Furthermore, more active sites and the greater electrical conductivity of TCPP/Ce-CoCu-LDH also contributed to the high photoelectrocatalytic activity. Thus, TCPP/Ce-CoCu-LDH can be used as a low-cost alternative for Pt-based catalyst toward MOR.

CeO2/Co3O4@N-doped hollow carbon microspheres with improved peroxidase-like activity for the determination of quercetin.

Nanozymes, as substitutes for natural enzymes, have been used to construct some fast cheap sensing platforms by virtue of the high catalytic activity. Herein, we firstly study the peroxidase-like activity of CeO2/Co3O4@N-doped hollow carbon microspheres as nanozymes. In the presence of H2O2, CeO2/Co3O4@NCH exhibits high peroxidase-like activity evaluated by the catalytic oxidation of the chromogenic substrate, 3,3',5,5'-tetramethylbenzidine (TMB) into a blue oxTMB visually in 1 min. The larger surface area, pore-like structure, and oxygen vacancies contribute to the enhanced peroxidase-like activity of CeO2/Co3O4@NCH. The active species •O2- is detected during the catalytic process. Thus, based on the excellent peroxidase-like activity of CeO2/Co3O4@NCH, a facile and effective biosensor is fabricated for sensitive and selective determination of H2O2 and quercetin, respectively. CeO2/Co3O4@NCH shows high affinity towards H2O2 (Km = 4.001 mM) and TMB (Km = 0.086 mM). The detection limit of H2O2 and quercetin is as low as 0.086 mM and 1.19 µM (3σ/slope), respectively. This work remarkably extends the utilization of CeO2/Co3O4@NCH in designing a colorimetric sensing platform related to biosensing, food, and environmental monitoring. A fast colorimetric sensing platform for quercetin based on the excellent peroxidase-like activity of CeO2/Co3O4@NCH.

Photoelectrochemical thrombin biosensor based on perylene-3,4,9,10-tetracarboxylic acid and Au co-functionalized ZnO nanorods with signal-off quenching effect of Ag@Ag2S.

In this work, a thrombin photoelectrochemical aptasensor was reported based on a photoanode of perylene-3,4,9,10-tetracarboxylic acid (PTCA), Au nanoparticle co-functionalized ZnO nanorods (ZnO NRs) and the "signal-off" amplification effect of Ag@Ag2S. The photocurrent response of the ZnO NRs was improved greatly due to the excellent visible-light photoelectric performance of PTCA and the surface plasmon resonance (SPR) effect of Au nanoparticles. Due to the specific recognition between thrombin and aptamers, the non-conductive complex with a steric hindrance structure blocked the diffusion path of the electron donating ascorbic acid (AA) and then the "signal-off" Ag@Ag2S quencher was captured. The quencher blocked the irradiation light toward the ZnO NRs/PTCA/Au electrode and competitively consumed the electron donor AA that could have been involved in the oxidation reaction with photogenerated holes of PTCA, resulting in the further decrease of the photocurrent. Based on the evident photocurrent response of the photoanode and the superior quenching strategies, the detection limit of thrombin is as low as 33 fM with a wide linear detection range from 0.0001 nM to 50 nM. The prepared biosensor also exhibited good specificity, reproducibility and stability, suggesting potential application in thrombin specific detection.

5,10,15,20-tetrakis (4-carboxyl phenyl) porphyrin-functionalized urchin-like CuCo2O4 as an excellent artificial nanozyme for determination of dopamine.

Urchin-like peroxidase mimics 5,10,15,20-tetrakis (4-carboxyl phenyl) porphyrin-functionalized CuCo2O4 nanospheres (Por-CuCo2O4) has been fabricated as an excellent visual biosensor. X-ray diffractometry (XRD), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS) have been employed to characterize the composition, morphologies, and elemental analysis of the as-synthesized Por-CuCo2O4. The catalytic activity of Por-CuCo2O4 was evaluated by the chromogenic substrate 3,3',5,5'-tetramethylbenzidine (TMB) with the aid of H2O2, which exhibited a visual blue change with an absorption maximum at 652 nm for only 10 s. The peroxidase-like behaviors of Por-CuCo2O4 conformed to the Michaelis-Menten equation. Electrochemistry, radical scavenger, and fluorescence probe experiments verified that electron transfer, •O2- radicals, and holes (h+) are the important factors during the catalytic oxidation of TMB. Based on the inhibition of dopamine (DA) on TMB oxidation, the Por-CuCo2O4-based colorimetric biosensor has been successfully constructed for sensitive determination of DA witha detection limit (LOD) of 0.94 µΜ. In addition, colorimetry was validated to detect DA in serum samples with high sensitivity and good selectivity. 5,10,15,20-tetrakis (4-carboxyl phenyl) porphyrin-functionalized urchin-like CuCo2O4 (Por-CuCo2O4) with excellent peroxidase activity, ascribed to the synergistic effect between •O2- radicals and holes (h+). A fast colorimetric sensor on the basis of Por-CuCo2O4 has been constructed to quantitatively determine dopamine concentration in human serums.

Construction and validation of the CRISPR/dCas9-EZH2 system for targeted H3K27Me3 modification.

Cell phenotypes are closely related to the epigenome, which could be precisely regulated by the targeted manipulation of epigenetic marks. Here, we have successfully produced a targeted histone methylation system, which consists of nuclease-null dCas9 protein, the sgRNA fused with PP7 RNA aptamers and the Enhancer of Zeste Homolog 2 (EZH2) fused to PP7 coat protein (PCP). Guided by the dCas9/sgRNA-PP7, the PCP-EZH2 can specifically target gene loci to catalyze 3 methylation of histone H3 lysine 27, resulting in the inhibition of gene expression. This kind of gene inhibition system is supposed to be highly effective, specific and flexible. As a proof-of-concept study, sgRNA targeting C/ebpα promoter region was designed. In the cells co-infected with the dCas9, sgRNA/C/ebpα-PP7 and PCP-EZH2, the expression of C/ebpα gene was significantly reduced via induction of trimethylation to H3K27 on C/ebpα promoter, with the results epigenetically inherited in the daughter cells. In conclusion, our results successfully established a gene modification system consisting of dCas9/sgRNA-PP7 and PCP-EZH2, providing a robust tool for targeted manipulation of gene epigenetic modification and expression.

Pixelated Carrier Phase-Shifting Shearography Using Spatiotemporal Low-Pass Filtering Algorithm.

Shearography has been widely used in non-destructive testing due to its advantages in providing full-field, high precision, real-time measurement. The study presents a pixelated carrier phase-shifting shearography using a pixelated micropolarizer array. Based on the shearography, a series of shearograms are captured and phase maps corresponding to deformation are measured dynamically and continuously. Using the proposed spatiotemporal filtering algorithm in the complex domain, the set of phase maps are simultaneously low-pass filtered in the spatial and temporal domains, resulting in better phase quality than spatial low-pass filtering. By accumulating the temporally adjacent phase, the phase corresponding to large deformation can be evaluated; thus, large deformations can be accurately measured and protected from speckle noise, allowing internal defects to be easily identified. The capability of the proposed shearography is described by theoretical discussions and experiments.

Base-Mediated Defluorosilylation of C(sp2 )-F and C(sp3 )-F Bonds.

The ability to selectively forge C-heteroatom bonds by C-F scission is typically accomplished by metal catalysts, specialized ligands and/or harsh reaction conditions. Described herein is a base-mediated defluorosilylation of unactivated C(sp2 )-F and C(sp3 )-F bonds that obviates the need for metal catalysts. This protocol is characterized by its simplicity, mild reaction conditions, and wide scope, even within the context of late-stage functionalization, constituting a complementary approach to existing C-Si bond-forming protocols.

Acetaldehyde dehydrogenase 2 (ALDH2) deficiency exacerbates pressure overload-induced cardiac dysfunction by inhibiting Beclin-1 dependent autophagy pathway.

Mitochondrial aldehyde dehydrogenase 2 (ALDH2) was demonstrated to play cardioprotective roles in cardiovascular diseases. Nonetheless, little is known about the roles and mechanisms of ALDH2 in pressure overload-induced cardiac damages. In this study, we revealed that ALDH2 deficiency overtly exacerbated transverse aortic constriction (TAC)-induced cardiac dysfunction. Cardiomyocyte enlargement was observed in both WT and ALDH2-/- mice in HE-stained myocardial tissue samples at 8 weeks post TAC surgery. Mitochondrial morphology and structure were also significantly damaged post TAC surgery and the changes were aggravated in ALDH2-/- TAC hearts. ALDH2 deficiency also depressed myocardial autophagy in hearts at 8 weeks post TAC surgery with a potential mechanism of repressing the expression of Beclin-1 and promoting the interaction between Bcl-2 and Beclin-1. These data indicate that ALDH2 deficiency exacerbates the pressure overload induced cardiac dysfunction partly by inhibiting Beclin-1 dependent autophagy pathway. This article is part of a Special Issue entitled: Autophagy and protein quality control in cardiometabolic diseases.

Mitochondrial Aldehyde Dehydrogenase 2 Regulates Revascularization in Chronic Ischemia: Potential Impact on the Development of Coronary Collateral Circulation.

OBJECTIVE: Revascularization is an essential process to compensate for cardiac underperfusion and, therefore, preserves cardiac function in the face of chronic ischemic injury. Recent evidence suggested a vital role of aldehyde dehydrogenase 2 (ALDH2) in cardiac protection after ischemia. This study was designed to determine whether ALDH2 regulates chronic ischemia-induced angiogenesis and to explore the underlying mechanism involved. Moreover, the clinical impact of the ALDH2 mutant allele on the development of coronary collateral circulation (CCC) was evaluated. APPROACH AND RESULTS: Mice limb ischemia was performed. Compared with wild-type, ALDH2 deletion significantly reduced perfusion recovery, small artery and capillary density, and increased muscle atrophy in this ischemic model. In vitro, ALDH2-knockdown reduced proliferation, migration and hypoxia triggered endothelial tube formation of endothelial cells, the effects of which were restored by ALDH2 transfection. Further examination revealed that ALDH2 regulated angiogenesis possibly through hypoxia-inducible factor-1α/vascular endothelial growth factor pathways. To further discern the role of ALDH2 deficiency in the function of bone marrow stem/progenitor cells, cross bone marrow transplantation was performed between wild-type and ALDH2-knockout mice. However, there was no significant improvement for wild-type bone marrow transplantation into knockout mice. ALDH2 genotyping was screened in 139 patients with chronic total occlusion recruited to Zhongshan Hospital (2011.10-2014.4). Patients with poor CCC (Rentrop 0-1; n=51) exhibited a higher frequency of the AA genotype than those with enriched CCC (Rentrop 2-3; n=88; 11.76% versus 1.14%; P=0 0.01). However, the AA group displayed less enriched CCC frequency in Logistic regression model when compared with the GG group (odds ratio=0.08; 95% confidence interval, 0.009-0.701; P=0 0.026). Furthermore, serum vascular endothelial growth factor level tended to be lower in patients with ALDH2 mutation. CONCLUSIONS: This study demonstrated that ALDH2 possesses an intrinsic capacity to regulate angiogenesis via hypoxia-inducible factor-1α and vascular endothelial growth factor. Patients with ALDH2-deficient genotype displayed a higher risk of developing poor CCC. Therapeutic individualization based on ALDH2 allele distribution may thus improve the therapeutic benefit, especially in the East Asian decedents.

Trans-Fatty Acids Aggravate Obesity, Insulin Resistance and Hepatic Steatosis in C57BL/6 Mice, Possibly by Suppressing the IRS1 Dependent Pathway.

Trans-fatty acid consumption has been reported as a risk factor for metabolic disorders and targeted organ damages. Nonetheless, little is known about the roles and mechanisms of trans-fatty acids in obesity, insulin resistance (IR) and hepatic steatosis. Adult C57BL/6 male mice were fed with four different diets for 20 weeks: normal diet (ND), high fat diet (HFD), low trans-fatty acids diet (LTD) and high trans-fatty acid diet (HTD). The diet-induced metabolic disorders were assessed by evaluating body weight, glucose tolerance test, hepatic steatosis and plasma lipid profiles post 20-week diet. Histological (H&E, Oil-Red-O) staining and western blot analysis were employed to assess liver steatosis and potential signaling pathways. After 20-weeks of diet, the body weights of the four groups were 29.61 ± 1.89 g (ND), 39.04 ± 4.27 g (HFD), 34.09 ± 2.62 g (LTD) and 43.78 ± 4.27 g (HTD) (p < 0.05), respectively. HFD intake significantly impaired glucose tolerance, which was impaired further in the mice consuming the HTD diet. The effect was further exacerbated by HTD diet. Moreover, the HTD group exhibited significantly more severe liver steatosis compared with HFD group possibly through regulating adipose triglyceride lipase. The group consuming the HTD also exhibited significantly reduced levels of IRS1, phosphor-PKC and phosphor-AKT. These results support our hypothesis that consumption of a diet high in trans-fatty acids induces higher rates of obesity, IR and hepatic steatosis in male C57BL/6 mice, possibly by suppressing the IRS1dependent pathway.

Ni-Catalyzed Borylation of Aryl Fluorides via C-F Cleavage.

A Ni-catalyzed borylation via C-F activation is described. This protocol is distinguished by a wide scope, including unactivated fluoroarenes, without compromising its efficiency and scalability, thus representing a significant step-forward toward the implementation of C-F activation protocols.

Impact of chronic low to moderate alcohol consumption on blood lipid and heart energy profile in acetaldehyde dehydrogenase 2-deficient mice.

AIM: To investigate the roles of acetaldehyde dehydrogenase 2 (ALDH2), the key enzyme of ethanol metabolism, in chronic low to moderate alcohol consumption-induced heart protective effects in mice. METHODS: Twenty-one male wild-type (WT) or ALDH2-knockout (KO) mice were used in this study. In each genotype, 14 animals received alcohol (2.5%, 5% and 10% in week 1-3, respectively, and 18% in week 4-7), and 7 received water for 7 weeks. After the treatments, survival rate and general characteristics of the animals were evaluated. Serum ethanol and acetaldehyde levels and blood lipids were measured. Metabolomics was used to characterize the heart and serum metabolism profiles. RESULTS: Chronic alcohol intake decreased the survival rate of KO mice by 50%, and significantly decreased their body weight, but did not affect those of WT mice. Chronic alcohol intake significantly increased the serum ethanol levels in both WT and KO mice, but KO mice had significantly higher serum acetaldehyde levels than WT mice. Chronic alcohol intake significantly increased the serum HDL cholesterol levels in WT mice, and did not change the serum HDL cholesterol levels in KO mice. After chronic alcohol intake, WT and KO mice showed differential heart and serum metabolism profiles, including the 3 main energy substrate types (lipids, glucose and amino acids) and three carboxylic acid cycles. CONCLUSION: Low to moderate alcohol consumption increases HDL cholesterol levels and improves heart energy metabolism profile in WT mice but not in ALDH2-KO mice. Thus, preserved ALDH2 function is essential for the protective effect of low to moderate alcohol on the cardiovascular system.

Palladium-catalyzed C(sp(3))-H activation: a facile method for the synthesis of 3,4-dihydroquinolinone derivatives.

3,4-Dihydroquinolinones were synthesized by the palladium-catalyzed, oxidative-addition-initiated activation and arylation of inert C(sp(3) )H bonds. Pd(OAc)2 and P(o-tol)3 were used as the catalyst and ligand, respectively, to improve the efficiency of the reaction. A further advantage of this reaction is that it could be performed in air. A relatively rare seven-membered palladacycle was proposed as a key intermediate of the catalytic cycle.

Octadecyl-fibrous mesoporous silica nanospheres coated 96-blade thin-film microextraction for high-throughput analysis of phthalic acid esters in food and migration from food packages.

A high-throughput sample pre-treatment method combined with high-performance liquid chromatography (HPLC) was developed to analyze phthalates (PAEs) in food and food contact package samples. Thin film microextraction (TFME) in 96-blade format was used to pre-treat 96 samples simultaneously. Octadecyl groups functionalized fibrous mesoporous silica nanospheres, namely C18-FMSNs, were synthesized and used as TFME coating material. The coating was fabricated by spraying a slurry of C18-FMSNs and polyacrylontrile (PAN) mixture with a commercial portable spraypen. The prepared C18-FMSNs/PAN coatings exhibited good reproducibility, repeatability and reusability. The optimized TFME conditions for PAEs consisted of extraction at pH 4.0 for 50 min, and desorption by methanol/acetonitrile (25/75, V/V) for 40 min. The pretreatment time for each sample was approximately 1.3 min. This TFME-HPLC method showed good linearity for eight PAEs within the concentration range of 0.5-1000 ng mL-1, with the coefficients higher than 0.9972. The limits of detection and quantification were 0.096-0.26 ng mL-1 and 0.32-0.86 ng mL-1, respectively. The intra-day and inter-day RSD % were below 6.6 % and 8.4 %, respectively, indicating good precision. The PAEs analysis in real samples showed that dibutyl phthalate (DBP) of 2.3 ± 0.3 ng mL-1 and di-(2-ethylhexyl) phthalate (DEHP) of 5.5 ± 0.8 ng mL-1 in boxed milk, dimethyl phthalate (DMP) of 12.6 ± 0.8 ng mL-1, DBP of 3.2 ± 0.4 ng mL-1and DEHP of 14.3 ± 0.7 ng mL-1 in the simulated water migration of plastic box, as well as DMP of 19.0 ± 0.6 ng mL-1, DBP of 25.6 ± 0.9 ng mL-1 and DEHP of 49.5 ± 2.8 ng mL-1 in the simulated ethanol migration of plastic box were determined, respectively. In addition, the detection of PAEs in all the real samples showed good recovery ranging from 85.6 to 110 % and lower RSDs % (<7.2 %).

Comprehending the cuproptosis and cancer-immunity cycle network: delving into the immune landscape and its predictive role in breast cancer immunotherapy responses and clinical endpoints.

Background: The role of cuproptosis, a phenomenon associated with tumor metabolism and immunological identification, remains underexplored, particularly in relation to the cancer-immunity cycle (CIC) network. This study aims to rigorously examine the impact of the cuproptosis-CIC nexus on immune reactions and prognostic outcomes in patients with breast cancer (BC), striving to establish a comprehensive prognostic model. Methods: In the study, we segregated data obtained from TCGA, GEO, and ICGC using CICs retrieved from the TIP database. We constructed a genetic prognostic framework using the LASSO-Cox model, followed by its validation through Cox proportional hazards regression. This framework's validity was further confirmed with data from ICGC and GEO. Explorations of the tumor microenvironment were carried out through the application of ESTIMATE and CIBERSORT algorithms, as well as machine learning techniques, to identify potential treatment strategies. Single-cell sequencing methods were utilized to delineate the spatial distribution of key genes within the various cell types in the tumor milieu. To explore the critical role of the identified CICs, experiments were conducted focusing on cell survival and migration abilities. Results: In our research, we identified a set of 4 crucial cuproptosis-CICs that have a profound impact on patient longevity and their response to immunotherapy. By leveraging these identified CICs, we constructed a predictive model that efficiently estimates patient prognoses. Detailed analyses at the single-cell level showed that the significance of CICs. Experimental approaches, including CCK-8, Transwell, and wound healing assays, revealed that the protein HSPA9 restricts the growth and movement of breast cancer cells. Furthermore, our studies using immunofluorescence techniques demonstrated that suppressing HSPA9 leads to a notable increase in ceramide levels. Conclusion: This research outlines a network of cuproptosis-CICs and constructs a predictive nomogram. Our model holds great promise for healthcare professionals to personalize treatment approaches for individuals with breast cancer. The work provides insights into the complex relationship between the cuproptosis-CIC network and the cancer immune microenvironment, setting the stage for novel approaches to cancer immunotherapy. By focusing on the essential gene HSPA9 within the cancer-immunity cycle, this strategy has the potential to significantly improve the efficacy of treatments against breast cancer.

Analyzing psychological resilience in college students: A decision tree model.

In the evolving landscape of higher education, particularly in the post-pandemic era, it is crucial for college students to face societal challenges and achieve success by understanding and predicting psychological resilience. To deepen our understanding of psychological resilience, this study used a decision tree model to explore influencing factors. We surveyed 776 college students and collected data on demographic information, self-esteem, sense of school belonging, pro-environmental behavior, subjective well-being, internet game addiction, life autonomy, and academic procrastination using several scales. The decision tree model identified eight key predictors of psychological resilience, which are as follows in order of importance: self-esteem, sense of school belonging, pro-environmental behavior, subjective well-being, academic procrastination, life autonomy, internet game addiction, and academic achievement. This model's accuracy reached 73.985 %, emphasizing its potential utility in educational settings. The findings not only provide a novel and data-driven perspective to understand psychological resilience in college students compared to existing research but also provide practical guidance for educational practitioners and policymakers on how to develop psychological resilience in college students.

Short-term efficacy and safety of neoadjuvant pyrotinib plus taxanes for early HER2-positive breast cancer: a single-arm exploratory phase II trial.

Background: The effectiveness and safety of pyrotinib have been substantiated in human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (BC). However, the role of pyrotinib as a single HER2 blockade in neoadjuvant setting among BC patients has not been studied. The objective of this study was to evaluate the efficacy and tolerability of pyrotinib plus taxanes as a novel neoadjuvant regimen in patients with HER2-positive early or locally advanced BC. Methods: In this single-arm exploratory phase II trial, patients with treatment-naïve HER2-positive BC (stage IIA-IIIC) received pyrotinib 400 mg once daily and taxanes [docetaxel 75 mg/m2 or nanoparticle albumin-bound (nab)-paclitaxel 260 mg/m2 every 3 weeks, or paclitaxel 80 mg/m2 weekly] for a total of four 21-day cycles before surgery. Efficacy assessment was based on pathological and clinical measurements. The primary endpoint of this study was the total pathological complete response (tpCR) rate. The secondary endpoints included breast pCR (bpCR) rate, investigator-assessed objective response rate (ORR) and adverse events (AEs) profiles. Results: From 1 September 2021 to 30 December 2022, a total of 31 patients were enrolled. One patient was withdrawn due to unbearable skin rash after the second cycle of neoadjuvant therapy. The majority of the intention-to-treat (ITT) population was premenopausal (54.8%), had large tumors (90.3%) and metastatic nodes (58.1%) at diagnosis and hormone-receptor positive tumors (64.5%). Most participants used nab-paclitaxel (74.2%) and received mastectomy (67.7%) after neoadjuvant treatment. The tpCR and bpCR rates were 48.4% [95% confidence interval (CI): 30.8-66%] and 51.6% (95% CI: 34-69.2%), respectively. Grade ≥3 treatment-related AEs were observed in 16.1% (5/31) of the ITT population, including diarrhea (n=2, 6.5%), hand and foot numbness (n=1, 3.2%), loss of appetite (n=1, 3.2%), and skin rash (n=1, 3.2%). AE related dose reduction or pyrotinib interruption was not required. Conclusions: In female patients with HER2-positive non-metastatic BC, neoadjuvant pyrotinib monotherapy plus taxanes appears to show promising clinical benefit and controllable AEs [Chinese Clinical Trial Registry (ChiCTR2100050870)]. The long-term efficacy and safety of this regime warrant further verification.

An organocatalyst bearing stereogenic carbon and sulfur centers as an efficient promoter for enantioselective hydrosilylation of 1,4-benzooxazines.

The efficient and enantioselective hydrosilylation of 3-aryl-1,4-benzooxazines was achieved using an l-phenyl alanine derived new Lewis base catalyst bearing stereogenic carbon and sulfur centers. In the presence of 2 mol % of catalyst, a broad range of 3-aryl-1,4-benzooxazines were hydrosilylated to afford the corresponding chiral 3-aryl-3,4-dihydro-2H-1,4-benzooxazine products with good to high yields (66-98%) and enantioselectivities (70-99% ee). This method provides an alternative approach with great practical application potential to access chiral 3-aryl-3,4-dihydro-2H-1,4-benzooxazines.