Atroposelective N-N Axes Synthesis via Electrochemical Cobalt Catalysis.

Here, we disclosed an unprecedented cobalt electrocatalyzed atroposelective C-H activation and annulation for the efficient construction of diversely functionalized N-N axes in an undivided cell. A broad range of allene substrates and benzamides bearing different functionalities are compatible with generating axially chiral products with good yields and excellent enantioselectivities (up to 92% yield and 99% ee). A series of synthetic applications and control experiments were also performed, which further expanded the practicality of this strategy.

Predictive value of Caprini risk assessment model, D-dimer, and fibrinogen levels on lower extremity deep vein thrombosis in patients with spontaneous intracerebral hemorrhage.

Introduction: Research indicates that individuals experiencing hemorrhagic stroke face a greater likelihood of developing lower extremity deep vein thrombosis (DVT) compared to those with ischemic stroke. This study aimed to assess the predictive capacity of the Caprini risk assessment model (RAM), D-dimer (D-D) levels, and fibrinogen (FIB) levels for lower extremity DVT in patients with spontaneous intracerebral hemorrhage (sICH). Methodology: This study involved a retrospective analysis of medical records from all sICH patients admitted to Shanghai General Hospital between June 2020 and June 2023. Within 48 h of admission, patients underwent routine screening via color Doppler ultrasonography (CDUS). Patients were categorized into the DVT and control groups based on the occurrence of lower extremity DVT during hospitalization. Differences in Caprini RAM, D-dimer, and FIB levels between the two groups were compared. The sensitivity and specificity of combined Caprini RAM, peripheral blood D-dimer, and FIB levels in predicting lower extremity DVT in sICH patients were analyzed. Receiver operating characteristic (ROC) curves assessed the overall predictive accuracy of Caprini RAM, D-D, and FIB levels. Results: The study involving 842 sICH patients revealed 225 patients with DVT and 617 patients without DVT. Caprini RAM, D-D, and FIB levels were significantly higher in the DVT group compared to the control group (P < 0.05). Sensitivity values for Caprini RAM, D-D, and FIB levels in predicting lower extremity DVT in sICH patients were 0.920, 0.893, and 0.680, respectively, while specificities were 0.840, 0.680, and 0.747, respectively. The ROC curve analysis demonstrated an area under the curve (AUC) of 0.947 for combined DVT prediction, with 97.33% sensitivity and 92.00% specificity, indicating superior predictive value compared to individual applications of Caprini RAM, D-D, and FIB levels. Conclusion: The combined utilization of Caprini RAM, D-D, and FIB levels holds significant clinical relevance in predicting lower extremity DVT in sICH patients.

Study on regulating AQP1, AQP3, AQP4, 5-HT, NOS1 in slow transit constipation rats by Liqi Tongbian mixture.

BACKGROUND: Liqi Tongbian is a traditional Chinese medicine (TCM) preparation that contains herbs that may treat slow transit constipation (STC). Atractylodes macrocephala, Astragalus membranaceus, Fructus aurantii, radish seed, uncooked Polygonum multiflorum, and Agastache rugosa were included in the formula for their unique qualities. The control of water transfer in the colon is greatly influenced by aquaporin 3 (AQP3). OBJECTIVES: Based on this, the Liqi Tongbian mixture was used to detect the concentrations of aquaporins (AQPs), 5-HT and nitrix oxide synthase 1 (NOS1) in STC rats, and explore its effect, in order to provide a theoretical basis for the remedy of STC with TCM. MATERIAL AND METHODS: Zhejiang University of Traditional Chinese Medicine provided 32 three-week-old Sprague Dawley rats of SPF-grade. The pairs licensed under SYXK (Zhejiang) 2021-0012 were kept at 20-25°C and humidity of 50-65%. The compound diphenoxylate caused constipation in the control, model, Liqi laxative (LQTB), and mosapride groups. The Liqi laxative rats were administered a mixture of traditional Chinese herbs after modeling, while mosapride was given to the other group. The levels of 5-HT, NOS1 and AQPs were tested in the feces and intestinal tissues. RESULTS: Comparing the condition of rat feces, it was found that the model group had significantly lower overall bulk, score and particles within 24 h compared to the control group. In comparison to mosapride, LQTB performed better. The model group had higher levels of 5-HT and NOS1 in intestinal tissue, while the LQTB and mosapride groups had decreased levels of these AQPs. LQTB had lower levels of AQP1, AQP3 and AQP4 than mosapride, while the model group had higher levels of these AQPs. CONCLUSIONS: Liqi Tongbian mixture works better than mosapride in improving constipation symptoms in rats with STC, and its mechanism is related to regulating the level of intestinal AQPs and neurotransmitters.

Extracellular vesicle-mediated communication between CD8+ cytotoxic T cells and tumor cells.

Tumors pose a significant global public health challenge, resulting in numerous fatalities annually. CD8+ T cells play a crucial role in combating tumors; however, their effectiveness is compromised by the tumor itself and the tumor microenvironment (TME), resulting in reduced efficacy of immunotherapy. In this dynamic interplay, extracellular vesicles (EVs) have emerged as pivotal mediators, facilitating direct and indirect communication between tumors and CD8+ T cells. In this article, we provide an overview of how tumor-derived EVs directly regulate CD8+ T cell function by carrying bioactive molecules they carry internally and on their surface. Simultaneously, these EVs modulate the TME, indirectly influencing the efficiency of CD8+ T cell responses. Furthermore, EVs derived from CD8+ T cells exhibit a dual role: they promote tumor immune evasion while also enhancing antitumor activity. Finally, we briefly discuss current prevailing approaches that utilize functionalized EVs based on tumor-targeted therapy and tumor immunotherapy. These approaches aim to present novel perspectives for EV-based tumor treatment strategies, demonstrating potential for advancements in the field.

High-Quality Solution-Processed Quasi-2D Perovskite for Low-Threshold Lasers.

Spin-coated quasi-two-dimensional halide perovskite films, which exhibit superior optoelectronic properties and environmental stability, have recently been extensively studied for lasers. Crystallinity is of great importance for the laser performance. Although some parameters related to the spin-coating process have been studied, the in-depth understanding and effective control of the acceleration rate on two-dimensional perovskite crystallization during spin-coating are still unknown. Here we investigate the effect of solvent evaporation on the microstructure of the final perovskite films during the spin-coating process. The crystallization quality of the film can be significantly improved by controlling solvent evaporation. As a result, the prepared quasi-2D perovskite film exhibits a stimulated emission threshold (pump: 343 nm, 6 kHz, 290 fs) of 550 nm as low as 16.2 µJ/cm2. Transient absorption characterization shows that the radiative biexciton recombination time is reduced from 738.5 to 438.3 ps, benefiting from the improved crystallinity. The faster biexciton recombination significantly enhanced the photoluminescence efficiency, which is critical for population inversion. This work could contribute to the development of low-threshold lasers.

High-Q two-dimensional perovskite topological laser.

Quasi-two-dimensional perovskites have attracted widespread interest in developing low-cost high-quality small lasers. The nano cavity based on topologically protected valley edge states can be robust against special defects. Here, we report a high-quality two-dimensional perovskite topological photonic crystal laser based on the quantum valley Hall effect. By adjusting the position of the air holes relative to the pillar, radiation leakage in topological edge states is reduced to a large extent, electric field distribution becomes more uniform and the quality factor can be as high as 3.6 × 104. Our findings could provide opportunities for the development of high-power, stable perovskite lasers with topological protection.

Investigating mobile persuasive design for mental wellness: A cross-domain analysis.

BACKGROUND: Global mental health issues have increased the demand for digital mental health support. Mobile apps with persuasive technology play a vital role in enhancing mental well-being. OBJECTIVE: Analysing and Comparing persuasive intervention design across various app categories, this study aims to inspire innovative design approaches for improving the persuasiveness of mental wellness apps during their development. METHODS: We retrieved a total of 100 mobile apps from five distinct categories (20 for each): Mental wellness, Social media, Entertainment, Fitness & Physical health and News & Information from Apple Store and Google Play. Two researchers examined and coded the apps to identify the persuasive features employed within each category using the Persuasive Systems Design (PSD) Framework, while a third researcher participated in discussions to resolve discrepancies. Kendall's Rank Correlation Coefficient was performed to determine the relationship between persuasive features and effectiveness. RESULTS: Trustworthiness (n = 81), Liking (n = 78), Surface credibility (n = 71), Reminders (n = 63), and Reduction (n = 57) were the most widely implemented persuasive features. Dialogue support and system credibility support features were heavily used across different app types, while social support features were less commonly employed, particularly in mental health apps. A positive correlation was found between Surface credibility, Trustworthiness, Liking, Reminders, Self-monitoring, Expertise features and apps' effectiveness. CONCLUSION: Through a cross-domain analysis using the PSD framework to investigate persuasive feature implementations, the findings from this study offer design suggestions to create innovative and effective mobile apps promoting mental well-being.

Regio- and Atroposelective Ring-Opening of 1H-Benzo[4,5]oxazolopyridinones.

The development of new methods for regio- and stereoselective activation of C-O bonds in ethers holds significant promise for synthetic chemistry, offering advantages in terms of environmental sustainability and economic efficiency. Moreover, the C-N atropisomers represent a fascinating and crucial chiral system, extensively found in natural products, pharmaceutical leads, and the frameworks of advanced materials. In this work, we have introduced a nickel-catalyzed regio- and enantioselective carbon-oxygen arylation reaction for atroposelective synthesis of N-arylisoquinoline-1,3(2H,4H)-diones. The high regioselectivity of C-O cleavage benefits from the high stability of the in situ formed (amido)ethenolate via oxidative addition. Additionally, the self-activation of the aryl C-O bond facilitates the reaction under mild conditions, leading to outstanding enantioselectivities. The diverse post-functionalizations of the axially chiral isoquinoline-1,3(2H,4H)-diones further highlighted the utility of this protocol in preparing valuable C-N atropisomers, including the chiral phosphine ligands.

Redox-Regulated Synthetic Channels: Enabling Reversible Ion Transport by Modulating the Ion-Permeation Pathway.

Natural redox-regulated channel proteins often utilize disulfide bonds as redox sensors for adaptive regulation of channel conformations in response to diverse physiological environments. In this study, we developed novel synthetic ion channels capable of reversibly switching their ion-transport capabilities by incorporating multiple disulfide bonds into artificial systems. X-ray structural analysis and electrophysiological experiments demonstrated that these disulfide-bridged molecules possess well-defined tubular cavities and can be efficiently inserted into lipid bilayers to form artificial ion channels. More importantly, the disulfide bonds in these molecules serve as redox-tunable switches to regulate the formation and disruption of ion-permeation pathways, thereby achieving a transition in the transmembrane transport process between the ON and OFF states.

Coaxial Bright and Dark Field Optical Coherence Tomography.

To improve the signal collection efficiency of Optical Coherence Tomography (OCT) for biomedical applications. A novel coaxial optical design was implemented, utilizing a wavefront-division beam splitter in the sample arm with a 45-degree rod mirror. This design allowed for the simultaneous collection of bright and dark field signals. The bright field signal was detected within its circular aperture in a manner similar to standard OCT, while the dark field signal passed through an annular-shaped aperture and was collected by the same spectrometer via a fiber array. This new configuration improved the signal collection efficiency by ∼3 dB for typical biological tissues. Dark-field OCT images were found to provide higher resolution, contrast and distinct information compared to standard bright-field OCT. By compounding bright and dark field images, speckle noise was suppressed by ∼ √2 . These advantages were validated using Teflon phantoms, chicken breast ex vivo, and human skin in vivo. This new OCT configuration significantly enhances signal collection efficiency and image quality, offering great potential for improving OCT technology with better depth, contrast, resolution, speckles, and signal-to-noise ratio. We believe that the bright and dark field signals will enable more comprehensive tissue characterization with the angled scattered light. This advancement will greatly promote the OCT technology in various clinical and biomedical research applications.

The synbiotic combination of probiotics and inulin improves NAFLD though modulating gut microbiota.

Prebiotics can promote the growth of probiotics, cocombine of these is called synbiotics, and synbiotics is powerful regulators of gut microbiota. Intestinal microbiota plays an important role in nonalcoholic fatty liver disease (NAFLD), so synbiotics could be a therapeutic alternative. This study aims to investigate the effect of synbiotics combination of probiotics (Streptococcus Bifidobacterium and Streptococcus thermophilus) and prebiotics (Inulin) in vivo model of early NAFLD using yogurt as carrier. The results demonstrate that the yogurt with synbiotics combination group (HS) improves the biochemical indicators related to total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and insulin resistance (IR) in mice (P< .01). HS improves the development of lipid metabolism and inflammation by activating the AMPK and NFκB signaling pathway. In addition, HS restores the intestinal barrier dysfunction and inflammation caused by a high-fat diet. The 16S rRNA demonstrates that the gut microbiota composition of mice treated with HS is significantly altered specifically, the Firmicutes/Bacteroidetes ratio is significantly lower than in HFD-fed mice (P< .01). Our findings suggest the applicability of HS in preventing obesity-related NAFLD via its antioxidant, anti-inflammatory, and improved lipid metabolism by the gut-liver axis and provide a solid theoretical foundation for developing prebiotics for the prevention of NAFLD.

Bifidobacterium longum promotes postoperative liver function recovery in patients with hepatocellular carcinoma.

Timely liver function recovery (LFR) is crucial for postoperative hepatocellular carcinoma (HCC) patients. Here, we established the significance of LFR on patient long-term survival through retrospective and prospective cohorts and identified a key gut microbe, Bifidobacterium longum, depleted in patients with delayed recovery. Fecal microbiota transfer from HCC patients with delayed recovery to mice similarly impacted recovery time post hepatectomy. However, oral gavage of B. longum improved liver function and repair in these mice. In a clinical trial of HCC patients, orally administering a probiotic bacteria cocktail containing B. longum reduced the rates of delayed recovery, shortened hospital stays, and improved overall 1-year survival. These benefits, attributed to diminished liver inflammation, reduced liver fibrosis, and hepatocyte proliferation, were associated with changes in key metabolic pathways, including 5-hydroxytryptamine, secondary bile acids, and short-chain fatty acids. Our findings propose that gut microbiota modulation can enhance LFR, thereby improving postoperative outcomes for HCC patients.

Tailored Water-Soluble Covalent Organic Cages for Encapsulation of Pyrene and Information Encryption.

Forming pyridine salts to construct covalent organic cages is an effective strategy for constructing covalent cage compounds. Covalent organic cages based on pyridine salt structures are prone to form water-soluble supramolecular compounds. Herein, we designed and synthesized a triangular prism-shaped hexagonal cage with a larger cavity and relatively flexible conformation. The supramolecular cage structure was also applied to the encapsulation of pyrene and information encryption.

Analysis of mRNA and MicroRNA Expression Profiles of Nervous Tissues and Reproductive Tissues in Male Procambarus clarkii After Silencing IAG.

The insulin-like androgenic gland hormone gene (IAG), primarily expressed in the androgenic gland (AG), plays a crucial role in controlling male sex differentiation and maintaining male secondary sexual characteristics in decapods. In this study, we investigated the mRNA and microRNA expression profiles of male Procambarus clarkii to understand the transcriptomic regulatory mechanism of IAG after the injection of an efficient siRNA (GsiRNA) designed based on IAG. The results revealed that several differentially expressed genes were enriched in reproduction-related pathways, such as the wnt signaling pathway, MAPK signaling pathway, and GnRH signaling pathway. In the testis (Te), the injection of GsiRNA led to the up-regulation of many ovary-related genes and down-regulation of testis-related genes. Moreover, the brain (Br) and abdominal nerve cord (AN) appeared to be involved in the regulation of IAG, with numerous differentially expressed genes found in Br and AN. Notably, the expression of five neuropeptide genes, Crustacean hyperglycemic hormone, pigment-dispersing hormone, red pigment concentrating hormone precursor, corazonin, and gonadotropin-releasing hormone II receptor isoform X1 in Br/AN, was significantly changed. Additionally, three ovary-related miRNAs (miR-263a, miR-263b, miR-133) highly expressed in Te/AG showed significant up-regulation after GsiRNA injection. Furthermore, the long-term interference of GsiRNA was found to inhibit the development of male external sexual characteristics during the juvenile stage and delay it during the adult stage. This research provides valuable insights into the molecular regulatory mechanism and function of IAG in P. clarkii.

C-N Axially Chiral Heterobiaryl Isoquinolinone Skeletons Construction via Cobalt-Catalyzed Atroposelective C-H Activation/Annulation.

Herein, the atroposelective construction of isoquinolinones bearing a C-N chiral axis has been successfully developed via a Co-catalyzed C-H bond activation and annulation process. This conversion can be effectively carried out in an environmentally friendly oxygen atmosphere to generate the target C-N axially chiral frameworks with excellent reactivities and enantioselectivities (up to >99% ee) in the absence of any additives. Additionally, the current protocol has proved to be an alternative approach for the C-N axial architectures fabrication under electrochemical conditions for cobalt/Salox catalysis, and this strategy allowed the efficient and atom-economical synthesis of various axially chiral isoquinolinones under mild reaction conditions.

Cobalt-catalyzed atroposelective C-H activation/annulation to access N-N axially chiral frameworks.

The N-N atropisomer, as an important and intriguing chiral system, was widely present in natural products, pharmaceutical lead compounds, and advanced material skeletons. The anisotropic structural characteristics caused by its special axial rotation have always been one of the challenges that chemists strive to overcome. Herein, we report an efficient method for the enantioselective synthesis of N-N axially chiral frameworks via a cobalt-catalyzed atroposelective C-H activation/annulation process. The reaction proceeds under mild conditions by using Co(OAc)2·4H2O as the catalyst with a chiral salicyl-oxazoline (Salox) ligand and O2 as an oxidant, affording a variety of N-N axially chiral products with high yields and enantioselectivities. This protocol provides an efficient approach for the facile construction of N-N atropisomers and further expands the range of of N-N axially chiral derivatives. Additionally, under the conditions of electrocatalysis, the desired N-N axially chiral products were also successfully achieved with good to excellent efficiencies and enantioselectivities.

Silk fibroin-based embolic agent for transhepatic artery embolization with multiple therapeutic potentials.

BACKGROUND: The excellent physicochemical and biomedical properties make silk fibroin (SF) suitable for the development of biomedical materials. In this research, the silk fibroin microspheres (SFMS) were customized in two size ranges, and then carried gold nanoparticles or doxorubicin to evaluate the performance of drug loading and releasing. Embolization efficiency was evaluated in rat caudal artery and rabbit auricular artery, and the in vivo distribution of iodinated SFMS (125I/131I-SFMS) after embolization of rat hepatic artery was dynamically recorded by SPECT. Transhepatic arterial radioembolization (TARE) with 131I-SFMS was performed on rat models with liver cancer. The whole procedure of selective internal radiation was recorded with SPECT/CT, and the therapeutic effects were evaluated with 18 F-FDG PET/CT. Lastly, the enzymatic degradation was recorded and followed with the evaluation of particle size on clearance of sub-micron silk fibroin. RESULTS: SFMS were of smooth surface and regular shape with pervasive pores on the surface and inside the microspheres, and of suitable size range for TAE. Drug-loading functionalized SFMS with chemotherapy or radio-sensitization, and the enhanced therapeutic effects were proved in treating HUH-7 cells as lasting doxorubicin release or more lethal radiation. For artery embolization, SFMS effectively blocked the blood supply; when 131I-SFMS serving as the embolic agent, the good labeling stability and embolization performance guaranteed the favorable therapeutic effects in treating in situ liver tumor. At the 5th day post TARE with 37 MBq/3 mg 131I-SFMS per mice, tumor activity was quickly inhibited to a comparable glucose metabolism level with surrounding normal liver. More importantly, for the fragments of biodegradable SFMS, smaller sized SF (< 800 nm) metabolized in gastrointestinal tract and excreted by the urinary system, while SF (> 800 nm) entered the liver within 72 h for further metabolism. CONCLUSION: The feasibility of SFMS as degradable TARE agent for liver cancer was primarily proved as providing multiple therapeutic potentials.

Effect of weekend admission on mortality risk in patients with sepsis and septic shock: A systematic review and meta-analysis.

BACKGROUND: There is an ongoing debate if weekend admissions of critically ill patients are associated with higher mortality rates. The current review aimed to specifically assess this effect in sepsis and septic shock patients by comparing mortality rates with weekend versus weekday admissions. METHODS: PubMed, CENTRAL, Scopus, Web of Science, and Embase were searched up to 20th February 2023 with an additional search of Google Scholar for gray literature. RESULTS: Nine studies were eligible. Meta-analysis of all nine studies with data from 1,134,417 patients demonstrated that sepsis or septic shock patients admitted on weekends don't have higher mortality as compared to those admitted on weekdays (OR: 1.04; 95% CI: 1.00, 1.09; p = 0.05; I2 = 93%). On subgroup analysis based on sample size (>2000 or <2000 patients) and timing of mortality, we noted no difference in the significance of the results. However, there was a small significant increased risk of mortality with weekend admission noted in studies on the Asian population and including septic shock patients. CONCLUSION: Weekend admission does not have an adverse impact on mortality rates of sepsis and septic shock patients. Results must be interpreted with caution owing to high interstudy heterogeneity and variation in confounders adjusted by individual studies.

C-N Axially Chiral Heterobiaryl Skeletons Construction via Cobalt-Catalyzed Atroposelective Annulation.

Herein, the atroposelective construction of five-six heterobiaryl skeleton-based C-N chiral axis has been successfully accomplished via a Co-catalyzed C-H bond activation and annulation process, in which the isonitrile was employed as the C1 source and the 8-aminoquinoline moiety served as both directing group and integral part of C-N atropisomers, respectively. This conversion can be effectively carried out in an environmentally friendly oxygen atmosphere, generating the target axial heterobiaryls with excellent reactivities and enantioselectivities (up to >99% ee) in the absence of any additives, and the obtained 3-iminoisoindolinone products with a five membered N-heterocycle exhibit high atropostability. Additionally, the C-N axially chiral monophosphine backbones derived from this protocol possess the potential to become an alternative ligand platform.