[3 + 2] Cycloaddition Reaction of Vinylsulfonium Salts with Hydrazonoyl Halides: Synthesis of Pyrazoles.

An efficient [3 + 2] cycloaddition reaction between in situ generated nitrile imines from hydrazonoyl halides and vinylsulfonium salts is developed. The nitrile imines are demonstrated to be a new class of reaction partner for vinylsulfonium salts to conduct the [3 + 2] cycloaddition reaction. The process provides a concise and efficient method for the construction of pyrazole derivatives under mild reaction conditions with broad substrate scope, good product yields, and high regioselectivity.

Attenuating midline thalamus bursting to mitigate absence epilepsy.

Advancing the mechanistic understanding of absence epilepsy is crucial for developing new therapeutics, especially for patients unresponsive to current treatments. Utilizing a recently developed mouse model of absence epilepsy carrying the BK gain-of-function channelopathy D434G, here we report that attenuating the burst firing of midline thalamus (MLT) neurons effectively prevents absence seizures. We found that enhanced BK channel activity in the BK-D434G MLT neurons promotes synchronized bursting during the ictal phase of absence seizures. Modulating MLT neurons through pharmacological reagents, optogenetic stimulation, or deep brain stimulation effectively attenuates burst firing, leading to reduced absence seizure frequency and increased vigilance. Additionally, enhancing vigilance by amphetamine, a stimulant medication, or physical perturbation also effectively suppresses MLT bursting and prevents absence seizures. These findings suggest that the MLT is a promising target for clinical interventions. Our diverse approaches offer valuable insights for developing next generation therapeutics to treat absence epilepsy.

Fluoride-Mediated Aryne 1,2-Difunctionalization Involving C═S Bond Heterolysis.

We have successfully synthesized a series of bidentate ligands by utilizing 2-(trimethylsilyl)phenyl trifluorosulfonate as a precursor for the benzyl group. This method proceeded by inserting a polythiourea into the C═S π-bond, intramolecular ring proton migration, and ring opening. Salient features of this strategy are mild reaction conditions, a novel product structure, excellent stereochemistry, and a good functional group tolerance. Furthermore, a series of density functional theory calculations were performed to gain insights into the transfer mechanism.

Jingqianshu granules mitigates premenstrual depression by regulating orexin signaling.

Introduction: Premenstrual dysphoric disorder (PMDD), a severe form of premenstrual syndrome (PMS), is a serious health disorder that affects patient moods. It is caused by cyclic psychological symptoms and its pathogenesis is still unclear. Abnormalities in the basolateral amygdala (BLA) orexin system, which are important causes of the development of depressive mood, have not been reported in PMDD, so exploring its intrinsic mechanisms is meaningful for enriching the pathomechanisms of PMDD. Methods: High performance liquid chromatography was used for the determination of the active ingredients of Jingqianshu granules. Developing a rat model of premenstrual depression using the forced swimming test (FST). The experiment consisted of two parts. In Part 1, the rats were divided into the control group, the model group, the model + Jingqianshu group, and the model + fluoxetine group. The FST, open field test, and elevated plus maze test, were used to assess the behavior of the rats as well as to evaluate the effect of drug intervention. Immunofluorescence and RT-qPCR were used to detect the expression of orexin and its receptors OX1R and OX2R genes and proteins. The expression of Toll-like receptor 4, nuclear factor kappa-B, tumor necrosis factor-α, interleukin 6, and interleukin-1ß in the BLA brain region was detected by Western-Blot. In part 2, the rats were injected intracerebrally with orexin-A. Observe the behavioral activities of rats in the control group, model group, and model+orexin-A group. Immunofluorescence was used to detect microglia in the BLA area of rats, and the expression levels of the above inflammatory factors were detected by Western-Blot. Results: The five components of Jingqianshu granules are: paeoniflorin, erulic acid, liquiritin, hesperidin, and paeonol. During the estrous cycle, rats exhibited depressive-like behavior during the non-receptive phase of the behavioral test, which disappeared during the receptive phase. Immunofluorescence and RT-qPCR showed reduced gene and protein expression of orexin, OX1R, and OX2R in the BLA region of rats in the model group.WB showed elevated levels of inflammatory factors. All returned to control levels after drug treatment. In part 2, injection of orexin-A into the BLA brain region of model rats resulted in reduced immunoreactivity of microglia and decreased expression levels of inflammatory factors. Discussion: Jianqianshu granules can achieve the purpose of treating premenstrual depression by regulating orexin-mediated inflammatory factors, which provides a new idea for further research on the pathogenesis of PMDD. However, the current study is still preliminary and the pathogenesis of PMDD is complex. Therefore, more in-depth exploration is needed.

TMEM16F scramblase regulates angiogenesis via endothelial intracellular signaling.

TMEM16F, a Ca2+-activated lipid scramblase (CaPLSase) that dynamically disrupts lipid asymmetry, plays a crucial role in various physiological and pathological processes such as blood coagulation, neurodegeneration, cell-cell fusion, and viral infection. However, the mechanisms through which it regulates these processes remain largely elusive. Using endothelial cell-mediated angiogenesis as a model, here we report a previously unknown intracellular signaling function of TMEM16F. We demonstrate that TMEM16F deficiency impairs developmental retinal angiogenesis in mice and disrupts angiogenic processes in vitro. Biochemical analyses indicate that the absence of TMEM16F enhances the plasma membrane association of activated Src kinase. This in turn increases VE-cadherin phosphorylation and downregulation, accompanied by suppressed angiogenesis. Our findings not only highlight TMEM16F's intracellular signaling role in endothelial cells but also open new avenues for exploring the regulatory mechanisms of membrane lipid asymmetry and their implications in disease pathogenesis.

Synthesis and Characterization of Emulsifiers Based on the Maillard Reaction and Its Application in Stabilized DHA Algal Oil Nanoemulsions.

The aim of this study was to optimize the formation of sodium caseinate (CS) and gum arabic (GA) complexes through the Maillard reaction and to evaluate their effectiveness in improving the emulsification properties and stability of docosahexaenoic acid (DHA) nanoemulsions. First, the best target polysaccharides were selected, and the best modification conditions were determined using orthogonal experiments. Secondly, the response surface experiments were used to optimize the preparation process of the emulsion. The stability, in vitro digestion characteristics, and rheological characteristics of the emulsion prepared by means of CS-GA were compared with the emulsion prepared using a whey protein isolate (WPI). After the orthogonal test, the optimal modification conditions were determined to be a reaction time of 96 h, a CS-GA mass ratio of 1:2, a reaction temperature of 60 °C, and a degree of grafting of 44.91%. Changes in the infrared (IR), Raman, ultraviolet (UV), and endogenous fluorescence spectra also indicated that the complex structure was modified. The response surface test identified the optimal preparation process as follows: an emulsifier concentration of 5 g/L, an oil-phase concentration of 5 g/L, and a homogenization frequency of five, and the emulsion showed good stability. Therefore, the use of a nanoemulsion as a nanoscale DHA algal oil delivery system is very promising for extending the shelf life and improving the stability of food.

Palladium-Catalyzed Three-Component Cascade Carbonylation Reaction to Construct Benzofuran Derivatives.

A novel three-component cyclization carbonylation reaction of iodoarene-tethered propargyl ethers with amine and CO is reported. This palladium-catalyzed cascade reaction undergoes a sequence of oxidative addition, unsaturated bond migration, carbonyl insertion, and nucleophilic attack to deliver the benzofuran skeleton. Both aromatic amines and aliphatic amines could proceed smoothly in this transformation under one atm of CO.

TRIM21-mediated ubiquitylation of TAT suppresses liver metastasis in gallbladder cancer.

Liver metastasis is common in patients with gallbladder cancer (GBC), imposing a significant challenge in clinical management and serving as a poor prognostic indicator. However, the mechanisms underlying liver metastasis remain largely unknown. Here, we report a crucial role of tyrosine aminotransferase (TAT) in liver metastasis of GBC. TAT is frequently up-regulated in GBC tissues. Increased TAT expression is associated with frequent liver metastasis and poor prognosis of GBC patients. Overexpression of TAT promotes GBC cell migration and invasion in vitro, as well as liver metastasis in vivo. TAT knockdown has the opposite effects. Intriguingly, TAT promotes liver metastasis of GBC by potentiating cardiolipin-dependent mitophagy. Mechanistically, TAT directly binds to cardiolipin and leads to cardiolipin externalization and subsequent mitophagy. Moreover, TRIM21 (Tripartite Motif Containing 21), an E3 ubiquitin ligase, interacts with TAT. The histine residues 336 and 338 at TRIM21 are essential for this binding. TRIM21 preferentially adds the lysine 63 (K63)-linked ubiquitin chains on TAT principally at K136. TRIM21-mediated TAT ubiquitination impairs its dimerization and mitochondrial location, subsequently inhibiting tumor invasion and migration of GBC cells. Therefore, our study identifies TAT as a novel driver of GBC liver metastasis, emphasizing its potential as a therapeutic target.

Efficacy and Safety of High-Viscosity Bone Cement in Percutaneous Vertebroplasty for Kummell's Disease.

Background: To analyze and evaluate the clinical outcomes of using high-viscosity bone cement compared to low-viscosity bone cement in percutaneous vertebroplasty (PVP) for treatment of Kummell's disease. Methods: From July 2017 to July 2019, 68 Kummell's disease patients who underwent PVP were chosen and separated into 2 groups: H group (n = 34), were treated with high-viscosity bone cement and L group (n = 34), treated with low-viscosity bone cement during treatment. The operation time, number of fluoroscopy tests done, and amount of bone cement perfusion were recorded for both groups. Clinical outcomes were compared, by measuring their Visual Analog Scale (VAS), Oswestry Disability Index (ODI), Kyphosis Cobb's angle, vertebral height compression rate, and other complications. Results: High-viscosity group showed less operation time and reduced number of fluoroscopy tests than the low-viscosity group (P < 0.05). When compared to preoperative period, both groups' VAS and ODI scores were significantly reduced at 1 day and 1 year postoperatively (P < 0.05). The vertebral height compression rate and Cobb's angle were significantly lower (P < 0.05) in both groups after surgery compared with those before surgery (P < 0.05). The cement leakage rate in group H was 26.5%, which was significantly lower than that in group L, which was 61.8% (P < 0.05). Conclusions: High-viscosity and low-viscosity bone cement in PVP have similar clinical efficacy in reducing pain in patients during the treatment, but in contrast, high-viscosity bone cement shortens the operative time, reduces number of fluoroscopy views and vertebral cement leakage and improves surgical safety.

Transareolar Video-Assisted Thoracoscopic Surgery in Females: A Novel Incision for Pulmonary Ground Glass Nodule Resection.

Purpose: Uniportal video-assisted thoracoscopic surgery (VATS) is recognized for its minimally invasive nature, widely adopted globally. However, the evident scarring it leaves often triggers psychological apprehension and resistance to surgery. Transareolar incision, known for its superior cosmetic outcome with no visible scars, poses challenges in women due to the risk of mammary gland damage. In this report, we present successful pulmonary ground glass nodule (GGN) resection using transareolar VATS in female patients, aiming to address these concerns. Materials and Methods: We retrospectively analyzed the clinical data of 35 female patients who underwent GGN resection through transareolar VATS between August 2020 and March 2022. Results: There were no serious complications or perioperative deaths in this cohort of 35 female patients undergoing GGN resection through transareolar VATS. The operations, including local resection or segmentectomy, had an average duration of 70.1 ± 26.4 minutes, with a tube duration of 4.7 ± 2.1 days and a hospitalization time of 7.2 ± 2.3 days. The surgical approach varied, with 21 cases using transareolar uniport, 8 cases assisted by a 3-mm tiny port, and 6 cases converted to two-port VATS. Scar outcomes varied, with 21 cases showing no scar, 8 cases displaying a microscar, and 6 cases presenting a dominant scar of 1.7 ± 0.5 cm. Postoperative pain scores at 1 week and 1 month were 1.9 ± 0.9 and 1.0 ± 0.9, respectively, and the wound numbness occurred in 2.86% (1/35) of cases. Regarding breast complications, 2 patients suffered delayed healing of the incision. No damage and inflammation of glands were detected by breast B-mode ultrasonography. Conclusions: The transareolar incision emerges as a novel approach for VATS in female patients, offering advantages in terms of pain management and cosmetic outcomes.

Characterization of Flavor Profile of Sauced Pork from Different Regions of China Based on E-Nose, E-Tongue and Gas Chromatography-Ion Mobility Spectroscopy.

This study aimed to investigate the volatile flavor compounds and tastes of six kinds of sauced pork from the southwest and eastern coastal areas of China using gas chromatography-ion mobility spectroscopy (GC-IMS) combined with an electronic nose (E-nose) and electronic tongue (E-tongue). The results showed that the combined use of the E-nose and E-tongue could effectively identify different kinds of sauced pork. A total of 52 volatile flavor compounds were identified, with aldehydes being the main flavor compounds in sauced pork. The relative odor activity value (ROAV) showed that seven key volatile compounds, including 2-methylbutanal, 2-ethyl-3, 5-dimethylpyrazine, 3-octanone, ethyl 3-methylbutanoate, dimethyl disulfide, 2,3-butanedione, and heptane, contributed the most to the flavor of sauced pork (ROAV ≥1). Multivariate data analysis showed that 13 volatile compounds with the variable importance in projection (VIP) values > 1 could be used as flavor markers to distinguish six kinds of sauced pork. Pearson correlation analysis revealed a significant link between the E-nose sensor and alcohols, aldehydes, terpenes, esters, and hetero-cycle compounds. The results of the current study provide insights into the volatile flavor compounds and tastes of sauced pork. Additionally, intelligent sensory technologies can be a promising tool for discriminating different types of sauced pork.

A case report: co-occurrence of probable Vogt-Koyanagi-Harada disease and diabetic retinopathy.

BACKGROUND: Bilateral retinal detachment and choroidal detachment in a patient are rare occurrences. The presence of bilateral diabetic retinopathy (DR) in such a case is even rarer and complicates the condition. CASE PRESENTATION: In this study, we document a case of unconventional VKH. Manifestations in this patient included intense peripheral retinal detachment and choroidal detachment, along with vitreous opacities akin to cotton wool spots, concurrent with DR. The diagnosis was considered as probable VKH with DR. Treatment according to VKH protocols, including high-dose corticosteroids, yielded positive results. CONCLUSIONS: VKH can co-occurrence with DR. VKH manifestations vary, and early, aggressive, and long-term treatment is essential. The complexity of treatment increases with concurrent DR, necessitating the use of immunosuppressants.

YOLOv8s-CGF: a lightweight model for wheat ear Fusarium head blight detection.

Fusarium head blight (FHB) is a destructive disease that affects wheat production. Detecting FHB accurately and rapidly is crucial for improving wheat yield. Traditional models are difficult to apply to mobile devices due to large parameters, high computation, and resource requirements. Therefore, this article proposes a lightweight detection method based on an improved YOLOv8s to facilitate the rapid deployment of the model on mobile terminals and improve the detection efficiency of wheat FHB. The proposed method introduced a C-FasterNet module, which replaced the C2f module in the backbone network. It helps reduce the number of parameters and the computational volume of the model. Additionally, the Conv in the backbone network is replaced with GhostConv, further reducing parameters and computation without significantly affecting detection accuracy. Thirdly, the introduction of the Focal CIoU loss function reduces the impact of sample imbalance on the detection results and accelerates the model convergence. Lastly, the large target detection head was removed from the model for lightweight. The experimental results show that the size of the improved model (YOLOv8s-CGF) is only 11.7 M, which accounts for 52.0% of the original model (YOLOv8s). The number of parameters is only 5.7 × 106 M, equivalent to 51.4% of the original model. The computational volume is only 21.1 GFLOPs, representing 74.3% of the original model. Moreover, the mean average precision (mAP@0.5) of the model is 99.492%, which is 0.003% higher than the original model, and the mAP@0.5:0.95 is 0.269% higher than the original model. Compared to other YOLO models, the improved lightweight model not only achieved the highest detection precision but also significantly reduced the number of parameters and model size. This provides a valuable reference for FHB detection in wheat ears and deployment on mobile terminals in field environments.

Pd(II)-Catalyzed 1,2-Oxyarylation of Alkenes with O-Acylhydroxylamines as the Oxygen Source.

O-Acylhydroxylamine has been widely employed as an electrophilic amination reagent in transition-metal-catalyzed C-N coupling reactions, but its use as an electrophilic oxygen source has not been disclosed. Here, we report a Pd-catalyzed 1,2-oxyarylation of alkenes with O-acylhydroxylamines as an oxidant and an oxygen source for the first time. With simple amide as the monodentate directing group, this method features a broad substrate scope, good functional group tolerance, and mild conditions.

Interaction between hydroxymethanesulfonic acid and several organic compounds and its atmospheric significance.

The interactions of the micro-mechanism of hydroxymethanesulfonic acid (HMSA) with the typical small organic molecule in atmospheric (X = methanol, formaldehyde, formic acid, methyl formate, dimethyl ether, acetone) has been investigated by density functional theory (DFT), quantum theory of atoms in molecules (QTAIM), Generalized Kohn-Sham Enery Decomposition Analysis (GKS-EDA) and the atmospheric clusters dynamic code (ACDC). The results of DFT show that the stable six- to eight-membered ring structures are easily formed in HMSA-X clusters. According to the topological analysis results of the AIM theory and the IRI method, a strong hydrogen bonding interaction is present in the complex. GKS-EDA results show that electrostatic energy is the main contributor to the interaction energy as it accounts for 51 %-55 % of the total attraction energy. The evaporation rates of HMSA-HMSA and HMSA-HCOOH clusters were much lower than those of the other HMSA complexes. In addition, the Gibbs energy of formation (ΔG) of HMSA-X dimers is investigated under atmosphere temperature T = 217-298 K and p = 0.19-1.0 atm, the ΔG decreased with decreasing of the atmosphere temperature and increased with the decrease of atmospheric pressure, indicating that the low temperature and high pressure may significantly facilitate to the formation of dimers.

Hydrazone Phosphaketene as a Synthetic Platform To Obtain Three Classes of 1,2,4-Diazaphosphol Derivatives by Switchable Chemoselectivity Strategies.

We introduce switchable chemoselectivity strategies based on the hydrazone phosphaketene intermediate to synthesize three classes of 1,2,4-diazaphosphol derivatives. First, the five-membered heterocyclic P and O anion intermediates acted as nucleophilic agents in the selective construction of C-P and C-O bonds. Second, the phosphinidene served as a phosphorus synthon, allowing for the formation of C-P and C-N bonds. Finally, a stepwise mechanism, supported by DFT calculations, was invoked to explain the reaction selectivity.

Acceptance of disability, attitudes toward disability, and coping in adolescents with visual impairments: A cross-lagged study.

PURPOSE/OBJECTIVE: This study aims to understand the reciprocal relationships among acceptance of disability, attitudes toward disability, and coping among Chinese adolescents with visual impairments. RESEARCH DESIGN: Adolescents with visual impairments (NT1 = 311, NT2 = 170) from four Chinese special education schools completed three questionnaires twice over 1 year. Cross-lagged panel modeling was carried out to analyze the questionnaire data. RESULTS: The findings revealed that attitudes toward disability and self-directed coping at Time 1 (T1) positively predicted acceptance of disability at Time 2 (T2). Self-directed coping at T1 positively predicted attitudes toward disability at T2, and attitudes toward disability at T1 negatively predicted relinquished-control coping at T2. CONCLUSION/IMPLICATIONS: Visually impaired adolescents' attitudes toward disability and coping serve as antecedents of their acceptance of disability. There is a positive reciprocal relationship between coping and attitudes toward disability. Psychological interventions aimed at optimizing psychosocial adjustment among students with visual impairments may benefit from targeting coping strategies and attitudes toward disability. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Hydrolysis reactivity reveals significant seasonal variation in the composition of organic peroxides in ambient PM2.5.

Atmospheric organic peroxides (POs) play a key role in the formation of O3 and secondary organic aerosol (SOA), impacting both air quality and human health. However, there still remain technical challenges in investigating the reactivity of POs in ambient aerosols due to the instability and lack of standards for POs, impeding accurate evaluation of their environmental impacts. In the present study, we conducted the first attempt to categorize and quantify POs in ambient PM2.5 through hydrolysis, which is an important transformation pathway for POs, thus revealing the reactivities of various POs. POs were generally categorized into hydrolyzable POs (HPO) and unhydrolyzable POs (UPO). HPO were further categorized into three groups: short-lifetime HPO (S-HPO), intermediate-lifetime HPO (I-HPO), and long-lifetime HPO (L-HPO). S-HPO and L-HPO are typically formed from Criegee intermediate (CI) and RO2 radical reactions, respectively. Results show that L-HPO are the most abundant HPO, indicating the dominant role of RO2 pathway in HPO formation. Despite their lower concentration compared to L-HPO, S-HPO make a major contribution to the HPO hydrolysis rate due to their faster rate constants. The hydrolysis of PM2.5 POs accounts for 19 % of the nighttime gas-phase H2O2 growth during the summer observation, constituting a noteworthy source of gas-phase H2O2 and contributing to the atmospheric oxidation capacity. Seasonal and weather conditions significantly impact the composition of POs, with HPO concentrations in summer being significantly higher than those in winter and elevated under rainy and nighttime conditions. POs are mainly composed of HPO in summer, while in winter, POs are dominated by UPO.

NK-cell-elicited gasdermin-D-dependent hepatocyte pyroptosis induces neutrophil extracellular traps that facilitate HBV-related acute-on-chronic liver failure.

BACKGROUND AND AIMS: HBV infection is a major etiology of acute-on-chronic liver failure (ACLF). At present, the pattern and regulation of hepatocyte death during HBV-ACLF progression are still undefined. Evaluating the mode of cell death and its inducers will provide new insights for developing therapeutic strategies targeting cell death. In this study, we aimed to elucidate whether and how immune landscapes trigger hepatocyte death and lead to the progression of HBV-related ACLF. APPROACH AND RESULTS: We identified that pyroptosis represented the main cell death pattern in the liver of patients with HBV-related ACLF. Deficiency of MHC-I in HBV-reactivated hepatocytes activated cytotoxic NK cells, which in turn operated in a perforin/granzyme-dependent manner to trigger GSDMD/caspase-8-dependent pyroptosis of hepatocytes. Neutrophils selectively accumulated in the pyroptotic liver, and HMGB1 derived from the pyroptotic liver constituted an important factor triggering the generation of pathogenic extracellular traps in neutrophils (NETs). Clinically, elevated plasma levels of myeloperoxidase-DNA complexes were a promising prognostic biomarker for HBV-related ACLF. More importantly, targeting GSDMD pyroptosis-HMGB1 release in the liver abrogates NETs that intercept the development of HBV-related ACLF. CONCLUSIONS: Studying the mechanisms that selectively modulate GSDMD-dependent pyroptosis, as well as its immune landscapes, will provide a novel strategy for restoring the liver function of patients with HBV-related ACLF.

Associations of Early Gut Microbiome and Metabolome with Growth and Body Composition of Preterm Infants Within the First 6 Months.

Objectives: This study aimed to explore the associations of growth and body composition with gut microbiome and metabolome in preterm infants. Materials and Methods: A prospective cohort study including 73 human milk-fed very preterm infants was conducted. During hospitalization, fecal samples were collected to detect microbes and metabolites using 16S rRNA gene sequencing and liquid chromatography-mass spectrometry. Growth and body composition indices were measured at term equivalent age (TEA) and 6 months of corrected age (CA). Associations of the fecal microbiome and metabolome profiles with growth and body composition indices, as well as their changes, were analyzed. Results: A higher abundance of Streptococcus was associated with a lower fat-free mass (FFM) z-score at 6 months of CA (p = 0.002) and a smaller increase in FFM z-score from TEA to 6 months of CA (p = 0.018). Higher levels of 3'-sialyllactose and 6'-sialyllactose (6'-SL) in feces were correlated with a lower z-score of percentage body fat (PBF) (p = 0.018 and 0.020, respectively) and a lower z-score of fat mass (p = 0.044 and 0.043, respectively) at 6 months of CA. A higher level of 6'-SL in feces was correlated with a greater increase in FFM z-score from TEA to 6 months of CA (p = 0.021). Conclusions: This study sheds light on the role of specific microbial-host interactions in metabolic changes in preterm infants, indicating the potential role of sialylated human milk oligosaccharides in optimizing body composition.