Cope Rearrangement of 1-Acyl-2-vinylcyclopropanes to Cyclohept-4-Enones.

Cycloheptenones are widespread in natural products and bioactive molecules. An efficient and convenient NaH-mediated Cope Rearrangement of doubly activated vinylcyclopropanes is reported for the synthesis of cyclohepten-4-ones. These flexible intramolecular reactions were applicable to a wide range of substrates and could be performed on gram scale. The derivatization of the product leads to short and highly efficient synthesis of some useful functional molecules.

Integrative Metabolome and Transcriptome Analyses Provide Insights into Carotenoid Variation in Different-Colored Peppers.

Carotenoids are important pigments in pepper fruits. The colors of each pepper are mainly determined by the composition and content of carotenoid. The 'ZY' variety, which has yellow fruit, is a natural mutant derived from a branch mutant of 'ZR' with different colors. ZY and ZR exhibit obvious differences in fruit color, but no other obvious differences in other traits. To investigate the main reasons for the formation of different colored pepper fruits, transcriptome and metabolome analyses were performed in three developmental stages (S1-S3) in two cultivars. The results revealed that these structural genes (PSY1, CRTISO, CCD1, CYP97C1, VDE1, CCS, NCED1 and NCED2) related to carotenoid biosynthesis were expressed differentially in the two cultivars. Capsanthin and capsorubin mainly accumulated in ZR and were almost non-existent in ZY. S2 is the fruit color-changing stage; this may be a critical period for the development of different color formation of ZY and ZR. A combination of transcriptome and metabolome analyses indicated that CCS, NCED2, AAO4, VDE1 and CYP97C1 genes were key to the differences in the total carotenoid content. These new insights into pepper fruit coloration may help to improve fruit breeding strategies.

Efficient entry point encoding and decoding algorithms on 2D Hilbert space filling curve.

The Hilbert curve is an important method for mapping high-dimensional spatial information into one-dimensional spatial information while preserving the locality in the high-dimensional space. Entry points of a Hilbert curve can be used for image compression, dimensionality reduction, corrupted image detection and many other applications. As far as we know, there is no specific algorithms developed for entry points. To address this issue, in this paper we present an efficient entry point encoding algorithm (EP-HE) and a corresponding decoding algorithm (EP-HD). These two algorithms are efficient by exploiting the m consecutive 0s in the rear part of an entry point. We further found that the outputs of these two algorithms are a certain multiple of a certain bit of s, where s is the starting state of these m levels. Therefore, the results of these m levels can be directly calculated without iteratively encoding and decoding. The experimental results show that these two algorithms outperform their counterparts in terms of processing entry points.

HI-MViT: A lightweight model for explainable skin disease classification based on modified MobileViT.

Objective: To develop an explainable lightweight skin disease high-precision classification model that can be deployed to the mobile terminal. Methods: In this study, we present HI-MViT, a lightweight network for explainable skin disease classification based on Modified MobileViT. HI-MViT is mainly composed of ordinary convolution, Improved-MV2, MobileViT block, global pooling, and fully connected layers. Improved-MV2 uses the combination of shortcut and depth classifiable convolution to substantially decrease the amount of computation while ensuring the efficient implementation of information interaction and memory. The MobileViT block can efficiently encode local and global information. In addition, semantic feature dimensionality reduction visualization and class activation mapping visualization methods are used for HI-MViT to further understand the attention area of the model when learning skin lesion images. Results: The International Skin Imaging Collaboration has assembled and made available the ISIC series dataset. Experiments using the HI-MViT model on the ISIC-2018 dataset achieved scores of 0.931, 0.932, 0.961, and 0.977 on F1-Score, Accuracy, Average Precision (AP), and area under the curve (AUC). Compared with the top five algorithms of ISIC-2018 Task 3, Marco's average F1-Score, AP, and AUC have increased by 6.9%, 6.8%, and 0.8% compared with the suboptimal performance model. Compared with ConvNeXt, the most competitive convolutional neural network architecture, our model is 5.0%, 3.4%, 2.3%, and 2.2% higher in F1-Score, Accuracy, AP, and AUC, respectively. The experiments on the ISIC-2017 dataset also achieved excellent results, and all indicators were better than the top five algorithms of ISIC-2017 Task 3. Using the trained model to test on the PH2 dataset, an excellent performance score is obtained, which shows that it has good generalization performance. Conclusions: The skin disease classification model HI-MViT proposed in this article shows excellent classification performance and generalization performance in experiments. It demonstrates how the classification outcomes can be applied to dermatologists' computer-assisted diagnostics, enabling medical professionals to classify various dermoscopic images more rapidly and reliably.

Characterization of Plant Homeodomain Transcription Factor Genes Involved in Flower Development and Multiple Abiotic Stress Response in Pepper.

Plant homeodomain (PHD) transcription factor genes are involved in plant development and in a plant's response to stress. However, there are few reports about this gene family in peppers (Capsicum annuum L.). In this study, the pepper inbred line "Zunla-1" was used as the reference genome, and a total of 43 PHD genes were identified, and systematic analysis was performed to study the chromosomal location, evolutionary relationship, gene structure, domains, and upstream cis-regulatory elements of the CaPHD genes. The fewest CaPHD genes were located on chromosome 4, while the most were on chromosome 3. Genes with similar gene structures and domains were clustered together. Expression analysis showed that the expression of CaPHD genes was quite different in different tissues and in response to various stress treatments. The expression of CaPHD17 was different in the early stage of flower bud development in the near-isogenic cytoplasmic male-sterile inbred and the maintainer inbred lines. It is speculated that this gene is involved in the development of male sterility in pepper. CaPHD37 was significantly upregulated in leaves and roots after heat stress, and it is speculated that CaPHD37 plays an important role in tolerating heat stress in pepper; in addition, CaPHD9, CaPHD10, CaPHD11, CaPHD17, CaPHD19, CaPHD20, and CaPHD43 were not sensitive to abiotic stress or hormonal factors. This study will provide the basis for further research into the function of CaPHD genes in plant development and responses to abiotic stresses and hormones.

Anti-GPIb/IX autoantibodies are associated with poor response to dexamethasone combined with rituximab therapy in primary immune thrombocytopenia patients.

This retrospective study aimed to evaluate whether anti-glycoproteins (GPs) autoantibodies can be used as predictors of response to high-dose dexamethasone combined with rituximab (DXM-RTX) in the treatment of primary immune thrombocytopenia (ITP) patients. One-hundred twenty-six ITP patients were included and retrospectively analyzed, 66.7% of anti-GPIb/IX and 65.9% of anti-GPIIb/IIIa autoantibodies. Results showed that overall response (OR) and complete response (CR) rates of patients without anti-GPIb/IX autoantibodies to DXM-RTX were significantly higher than those with anti-GPIb/IX autoantibodies at 4 weeks (OR: 73.8% vs. 47.6%, CR: 50.0% vs. 26.2%; P < 0.05) and 6 months (OR: 71.4% vs. 45.2%, CR: 42.9% vs. 25.0%; P < .05). Furthermore, patients with anti-GPIb/IX single-positivity exhibited higher resistance to DXM-RTX than patients with anti-GPIIb/IIIa single-positivity at 4 weeks (OR: 37.5% vs. 78.3%; P < .05) and 6 months (OR: 29.2% vs. 78.3%; P < .05). Multivariable logistic regression analysis revealed that anti-GPIb/IX autoantibodies and megakaryocytes were associated with the OR rate of patients at both 4 weeks and 6 months, and anti-GPIb/IX autoantibodies at 4 weeks represented the only significant factor affecting OR rate with DXM-RTX (F = 9.128, P = .003). Therefore, platelet anti-GPIb/IX autoantibodies might predict poor response to DXM-RTX in ITP patients.

What is the context?The safety and efficacy of high-dose dexamethasone combined with rituximab (DXM-RTX) in the treatment of primary immune thrombocytopenia (ITP) are gradually recognized; however, there still needs to be an adequate clinical trial to predict its efficacy. Autoantibodies against platelet glycoproteins (GPs) are proven to be associated with a variety of therapeutic responses in ITP. Such as anti-GPIb/IX autoantibodies predict poor response to intravenous immunoglobulin G therapy and rhTPO therapy in ITP patients. Therefore, a retrospective study was needed to verify whether anti-GP autoantibodies can expect a response to DXM-RTX therapy in ITP patients.What is new?This study identified that anti-GPIb/IX autoantibodies were a predictive factor for poor response to DXM-RTX in ITP patients. It mainly manifested in the following aspects: (1) Overall response (OR) and complete response (CR) rates of patients without anti-GPIb/IX autoantibodies to DXM-RTX were significantly higher than those with anti-GPIb/IX autoantibodies at four weeks and six months. (2) Multivariable logistic regression analysis revealed that anti-GPIb/IX autoantibodies at both four weeks and six months were associated with the OR rate of patients.What is the impact?Our study suggests that ITP patients with anti-GPIb/IX positive autoantibodies respond poorly to DXM-RTX therapy. Platelet anti-GPIb/IX autoantibodies might predict poor response to DXM-RTX therapy in ITP patients.

Anion Cascade Reactions. Part I: Synthesis of 3-Isoquinuclidones from a Nazarov-like Reagent.

A simple and atom-economical one-step protocol is described for the synthesis of biologically valuable 3-isoquinuclidones. The method proceeds from the simple starting materials, α-acyl N-arylcinnamamides, and can be performed under mild conditions in the presence of tBuOK. The key steps of this process are the double Michael addition reaction of a Nazarov-like reagent and the subsequent intramolecular hemiamination. These flexible intermolecular reactions could be performed on a gram scale.

Palladium-catalyzed intramolecular aza-Wacker-type cyclization of vinyl cyclopropanecarboxamides to access conformationally restricted aza[3.1.0]bicycles.

A palladium(ii)-catalyzed intramolecular oxidative aza-Wacker-type reaction of vinyl cyclopropanecarboxamides to access a series of conformationally restricted highly substituted aza[3.1.0]bicycles is reported. The transformation proceeded through a typical aza-Wacker reaction mechanism to forge a new C-N bond with oxygen as the terminal oxidant. The desired fused heterocycles were obtained in moderate yields. The process is tolerant of a range of functional aryl groups under mild conditions.

Highly Efficient Visible-Blind Ultraviolet Photodetector Based on Scalably Produced Titanium Dioxide Nanowire Arrays.

Here, we report a novel, feasible, and cost-effective method for the preparation of one-dimensional TiO2 nanowire arrays using a super-aligned carbon nanotube film as a template. Pure-anatase-phase TiO2 nanowires were scalably prepared in a suspended manner, and a high-performance ultraviolet (UV) photodetector was realized on a flexible substrate. The large surface area and one-dimensional nanostructure of the TiO2 nanowire array led to a high detectivity (1.35 × 1016 Jones) and an ultrahigh photo gain (2.6 × 104), respectively. A high photoresponsivity of 7.7 × 103 A/W was achieved under 7 µW/cm2 UV (λ = 365 nm) illumination at a 10 V bias voltage, which is much higher than those of commercial UV photodetectors. Additionally, by taking advantage of its anisotropic geometry, we found the TiO2 nanowire array showed polarized photodetection. The concept of using nanomaterial systems shows the potential for realization of nanostructured photodetectors for practical applications.

Base-Promoted Intramolecular Addition of Vinyl Cyclopropanecarboxamides to Access Conformationally Restricted Aza[3.1.0]bicycles.

3-Azabicyclo[3.1.0]hexanes are common structural components in natural products and bioactive compounds. Traditionally, the metal-mediated cyclopropanation domino reaction of chain enzymes is the most commonly used strategy for the construction of this type of aza[3.1.0]bicycle derivative. In this study, a base-promoted intramolecular addition of alkenes used to deliver conformationally restricted highly substituted aza[3.1.0]bicycles is reported. This reaction was tailor-made for saturated aza[3.1.0] bicycle-containing fused bicyclic compounds that may be applied in the development of concise and divergent total syntheses of bioactive compounds.

The mechanism of chronic intracellular infection with Brucella spp.

Globally, brucellosis is a widespread zoonotic disease. It is prevalent in more than 170 countries and regions. It mostly damages an animal's reproductive system and causes extreme economic losses to the animal husbandry industry. Once inside cells, Brucella resides in a vacuole, designated the BCV, which interacts with components of the endocytic and secretory pathways to ensure bacterial survival. Numerous studies conducted recently have revealed that Brucella's ability to cause a chronic infection depends on how it interacts with the host. This paper describes the immune system, apoptosis, and metabolic control of host cells as part of the mechanism of Brucella survival in host cells. Brucella contributes to both the body's non-specific and specific immunity during chronic infection, and it can aid in its survival by causing the body's immune system to become suppressed. In addition, Brucella regulates apoptosis to avoid being detected by the host immune system. The BvrR/BvrS, VjbR, BlxR, and BPE123 proteins enable Brucella to fine-tune its metabolism while also ensuring its survival and replication and improving its ability to adapt to the intracellular environment.

"Less is better-Full-incision double-eyelid blepharoplasty with rapid recovery".

SUMMARY: Full-incision double eyelid blepharoplasty is effective, but its postoperative complications, such as local trauma and persistent tissue swelling, are major concerns for patients. Since tissue swelling is caused by the obstruction of blood and lymphatic flow, the authors modified the conventional full-incision method by minimizing the trauma as much as possible. Twenty-five patients underwent the modified procedure. There was minor swelling immediately after the surgery, which subsided 1-5 days after the surgery. No patient reported loss of the double eyelid crease. Only 2 patients underwent a second operation due to a low crease. The satisfactory ratio was 92% (23 of 25). According to our understanding of this technique, LESS trauma is the key to obtaining BETTER results under certain conditions.

Earlobe reconstruction with an inferior pedicle flap.

OBJECTIVE: This article describes an inferior pedicle flap for earlobe reconstruction. METHODS: The inferior pedicle flap was designed and marked according to the shape and size of the normal earlobe. The required flap was raised and folded to constitute a new earlobe and then sutured to the incised inferior edge of the earlobe defect. The donor site was directly closed. RESULTS: The reconstructed earlobe featured reliable vascularization and resulted in a natural appearance. No skin graft was needed for the donor site. The postoperative scars are short and concealed. CONCLUSIONS: The inferior pedicle flap is expected to provide a new idea for earlobe reconstruction.

Preclinical studies of a factor X activator and a phase 1 trial for hemophilia patients with inhibitors.

BACKGROUND: Bleeding episodes in hemophiliacs with inhibitors are difficult to control. Staidson protein-0601 (STSP-0601), a specific factor (F)X activator purified from the venom of Daboia russelii siamensis, has been developed. OBJECTIVES: We aimed to investigate the efficacy and safety of STSP-0601 in preclinical and clinical studies. METHODS: In vitro and in vivo preclinical studies were performed. A phase 1, first-in-human, multicenter, and open-label trial was conducted. The clinical study was divided into parts A and B. Hemophiliacs with inhibitors were eligible for this study. Patients received a single intravenous injection of STSP-0601 (0.01 U/kg, 0.04 U/kg, 0.08 U/kg, 0.16 U/kg, 0.32 U/kg, or 0.48 U/kg) in part A or a maximum of 6 4-hourly injections (0.16 U/kg) in part B. The primary endpoint for each part was the number of adverse events (AEs) from baseline to 168 hours after administration. This study was registered at clinicaltrials.gov (NCT-04747964 and NCT-05027230). RESULTS: Preclinical studies showed that STSP-0601 could specifically activate FX in a dose-dependent manner. In the clinical study, 16 patients in part A and 7 patients in part B were enrolled. Eight (22.2%) AEs in part A and 18 (75.0%) AEs in part B were reported to be related to STSP-0601. Neither severe AEs nor dose-limiting toxicity events were reported. There were no thromboembolic event. The antidrug antibody of STSP-0601 was not detected. CONCLUSION: Preclinical and clinical studies showed that STSP-0601 had a good ability to activate FX and had a good safety profile. STSP-0601 could be used as a hemostatic treatment in hemophiliacs with inhibitors.

Organocatalytic Cloke-Wilson Rearrangement: Carbocation-Initiated Tandem Ring Opening/Cyclization of Cyclopropanes under Neutral Conditions.

We report a metal-, acid-, and base-free 2-(bromomethyl)naphthalene (2-BMN)-promoted organocatalytic Cloke-Wilson rearrangement of chain doubly activated cyclopropanes for the construction of 2,3-dihydrofurans via a carbocation-initiated tandem intramolecular ring-opening/recyclization process. The strategy is especially suitable for the construction of furan units in complex molecules, providing a solution to the problem of heavy-metal residues in dihydrofuran-containing drugs synthesized by traditional metal-based protocols. Thus, it is of potential interest in synthetic and medicinal chemistry.

Holographically Activatable Nanoprobe via Glutathione/Albumin-Mediated Exponential Signal Amplification for High-Contrast Tumor Imaging.

Glutathione (GSH)-activatable probes hold great promise for in vivo cancer imaging, but are restricted by their dependence on non-selective intracellular GSH enrichment and uncontrollable background noise. Here, a holographically activatable nanoprobe caging manganese tetraoxide is shown for tumor-selective contrast enhancement in magnetic resonance imaging (MRI) through cooperative GSH/albumin-mediated cascade signal amplification in tumors and rapid elimination in normal tissues. Once targeting tumors, the endocytosed nanoprobe effectively senses the lysosomal microenvironment to undergo instantaneous decomposition into Mn2+ with threshold GSH concentration of ≈ 0.12 mm for brightening MRI signals, thus achieving high contrast tumor imaging and flexible monitoring of GSH-relevant cisplatin resistance during chemotherapy. Upon efficient up-regulation of extracellular GSH in tumor via exogenous injection, the relaxivity-silent interstitial nanoprobe remarkably evolves into Mn2+ that are further captured/retained and re-activated into ultrahigh-relaxivity-capable complex by stromal albumin in the tumor, and simultaneously allows the renal clearance of off-targeted nanoprobe in the form of Mn2+ via lymphatic vessels for suppressing background noise to distinguish tiny liver metastasis. These findings demonstrate the concept of holographic tumor activation via both tumor GSH/albumin-mediated cascade signal amplification and simultaneous background suppression for precise tumor malignancy detection, surveillance, and surgical guidance.

Graphene Microheater Chips for In Situ TEM.

Low-dimensional materials are bringing significant innovations to in situ TEM characterization. Here a new graphene microheater chip for TEM was developed by stacking graphene on a suspended SiNx membrane as the Joule heating element. It could be heated up to 800 °C within 26.31 ms with a low power consumption of 0.025 mW/1000 µm2. The bulging was only ∼50 nm at 650 °C, which is 2 orders of magnitude smaller than those of conventional MEMS heaters at similar temperatures. The performances benefit from the employment of graphene, since its monolayer structure greatly reduces the heat capacity, and the vdW contact significantly reduces the interfacial interaction. The TEM observation on the Sn melting process verifies its great potential in resolving thermodynamic processes. Moreover, more multifunctional in situ chips could be developed by integrating other stimuli to such chips. This work opens a new frontier for both graphene and in situ characterization techniques.

Inflammatory Mechanism of Brucella Infection in Placental Trophoblast Cells.

Brucellosis is a severe zoonotic infectious disease caused by the infection of the Brucella, which is widespread and causes considerable economic losses in underdeveloped areas. Brucella is a facultative intracellular bacteria whose main target cells for infection are macrophages, placental trophoblast cells and dendritic cells. The main clinical signs of Brucella infection in livestock are reproductive disorders and abortion. At present, the pathogenesis of placentitis or abortion caused by Brucella in livestock is not fully understood, and further research on the effect of Brucella on placental development is still necessary. This review will mainly introduce the research progress of Brucella infection of placental trophoblast cells as well as the inflammatory response caused by it, explaining the molecular regulation mechanism of Brucella leading to reproductive system disorders and abortion, and also to provide the scientific basis for revealing the pathogenesis and infection mechanism of Brucella.