Application Effects of Individualized Diet Nursing Combined with the Modified Glasgow-Blatchford Scoring System in Upper Gastrointestinal Bleeding.

Background: Upper gastrointestinal bleeding encompasses bleeding arising from esophageal, gastric, duodenal, or pancreaticobiliary lesions above the Treitz ligament. Research indicates a close association between improper diet and upper gastrointestinal bleeding. Objective: This study aims to investigate the application effects of individualized diet nursing combined with the modified Glasgow-Blatchford scoring system in patients with upper gastrointestinal bleeding. Design: A randomized controlled study was conducted. Setting: The study took place at the First Hospital of Hebei Medical University. Participants: From January 2021 to October 2022, 80 patients with upper gastrointestinal bleeding were selected at our hospital. Using a random number table, they were divided into a control group and an observation group, each comprising 40 cases. Interventions: The control group received routine nursing, while the observation group received individualized diet nursing based on the Glasgow-Blatchford score in addition to routine nursing. Primary Outcome Measures: (1) bleeding frequency, hemostasis time, and hospital stay; (2) re-bleeding rate; (3) Glasgow-Blatchford scores; (4) quality of life; and (5) nursing satisfaction. Results: In the observation group, bleeding frequency, hemostasis time, and hospital stay significantly reduced compared to the control (P < .05). Post-nursing, the observation group had a lower re-bleeding rate (χ2=11.25, P < .05). Before nursing, no statistical differences existed in Glasgow-Blatchford and quality of life scores between groups (P > .05). Post-nursing, both groups saw reduced Glasgow-Blatchford scores, more so in the observation group (P < .05). Quality of life scores increased in both, more notably in the observation group (P < .05). Overall nursing satisfaction was higher in the observation group (P < .05). Conclusions: Individualized diet nursing, based on the Glasgow-Blatchford score, improves cure rates and quality of life and warrants promotion.

Radical Three-Component Nitro Spiro-Cyclization of Unsaturated Sulfonamides/Amides to Access NO2-Featured 4-Azaspiro[4.5]decanes.

Free radical three-component nitration/spirocyclization of unsaturated sulfonamides/amides with tert-butyl nitrite was developed for the construction of diverse NO2-revised 4-azaspiro[4.5]decanes. This tandem system featured metal-free participation, simple operation, good selectivity/yields, and a green/low-cost O source. Meanwhile, one nitro-containing complex molecule and a scaled-up operation were performed well to test the synthetic potential of the cascade reaction. Isotopic labeling, radical inhibition experiments, and DFT analysis were carried out to gain insight into the reaction process.

Visible-Light-Mediated Three-Component Strategy for the Synthesis of Isoxazolines and Isoxazoles.

Isoxazolines and isoxazoles commonly serve as core structures of many therapeutic agents and natural products. However, the metal-free and catalysis-free strategy for the synthesis of these privileged motifs at room temperature remains a challenging task. Herein, we report a three-component strategy to afford diverse isoxazolines and isoxazoles via [3 + 2] cycloadditions of in situ-formed nitronates and olefins/alkynes under visible-light irradiation.

Acetone Serving as a Solvent and Interaction Partner Promotes the Direct Olefination of N-Tosylhydrazones under Visible Light.

The photochemistry of noncovalent interactions to promote organic transformations is an emerging approach to providing fresh opportunities in synthetic chemistry. Generally, the external substance is necessary to add as an interaction partner, thereby sacrificing the atom economy of the reaction. Herein, we describe a catalyst-free and noncovalent interaction-mediated strategy to access the olefination of N-tosylhydrazones using acetone as a solvent and an interaction partner. This protocol also features broad substrate scope, excellent functional group compatibility, and mild reaction conditions without transition metals. Moreover, the gram-scale synthesis of olefins and the generation of pharmaceutical intermediates highlighted its practical applicability. Lastly, mechanistic studies indicate that the reaction was initiated via noncovalent interactions between acetone and N-tosylhydrazone anion, which is also supported by density functional theory calculations.

Local delivery of stem cell spheroids with protein/polyphenol self-assembling armor to improve myocardial infarction treatment via immunoprotection and immunoregulation.

Stem cell therapies have shown great potential for treating myocardial infarction (MI) but are limited by low cell survival and compromised functionality due to the harsh microenvironment at the disease site. Here, we presented a Mesenchymal stem cell (MSC) spheroid-based strategy for MI treatment by introducing a protein/polyphenol self-assembling armor coating on the surface of cell spheroids, which showed significantly enhanced therapeutic efficacy by actively manipulating the hostile pathological MI microenvironment and enabling versatile functionality, including protecting the donor cells from host immune clearance, remodeling the ROS microenvironment and stimulating MSC's pro-healing paracrine secretion. The underlying mechanism was elucidated, wherein the armor protected to prolong MSCs residence at MI site, and triggered paracrine stimulation of MSCs towards immunoregulation and angiogenesis through inducing hypoxia to provoke glycolysis in stem cells. Furthermore, local delivery of coated MSC spheroids in MI rat significantly alleviated local inflammation and subsequent fibrosis via mediation macrophage polarization towards pro-healing M2 phenotype and improved cardiac function. In general, this study provided critical insight into the enhanced therapeutic efficacy of stem cell spheroids coated with a multifunctional armor. It potentially opens up a new avenue for designing immunomodulatory treatment for MI via stem cell therapy empowered by functional biomaterials.

Predicting sepsis in-hospital mortality with machine learning: a multi-center study using clinical and inflammatory biomarkers.

BACKGROUND: This study aimed to develop and validate an interpretable machine-learning model that utilizes clinical features and inflammatory biomarkers to predict the risk of in-hospital mortality in critically ill patients suffering from sepsis. METHODS: We enrolled all patients diagnosed with sepsis in the Medical Information Mart for Intensive Care IV (MIMIC-IV, v.2.0), eICU Collaborative Research Care (eICU-CRD 2.0), and the Amsterdam University Medical Centers databases (AmsterdamUMCdb 1.0.2). LASSO regression was employed for feature selection. Seven machine-learning methods were applied to develop prognostic models. The optimal model was chosen based on its accuracy, F1 score and area under curve (AUC) in the validation cohort. Moreover, we utilized the SHapley Additive exPlanations (SHAP) method to elucidate the effects of the features attributed to the model and analyze how individual features affect the model's output. Finally, Spearman correlation analysis examined the associations among continuous predictor variables. Restricted cubic splines (RCS) explored potential non-linear relationships between continuous risk factors and in-hospital mortality. RESULTS: 3535 patients with sepsis were eligible for participation in this study. The median age of the participants was 66 years (IQR, 55-77 years), and 56% were male. After selection, 12 of the 45 clinical parameters collected on the first day after ICU admission remained associated with prognosis and were used to develop machine-learning models. Among seven constructed models, the eXtreme Gradient Boosting (XGBoost) model achieved the best performance, with an AUC of 0.94 and an F1 score of 0.937 in the validation cohort. Feature importance analysis revealed that Age, AST, invasive ventilation treatment, and serum urea nitrogen (BUN) were the top four features of the XGBoost model with the most significant impact. Inflammatory biomarkers may have prognostic value. Furthermore, SHAP force analysis illustrated how the constructed model visualized the prediction of the model. CONCLUSIONS: This study demonstrated the potential of machine-learning approaches for early prediction of outcomes in patients with sepsis. The SHAP method could improve the interoperability of machine-learning models and help clinicians better understand the reasoning behind the outcome.

Insect cuticle-inspired design of sustainably sourced composite bioplastics with enhanced strength, toughness and stretch-strengthening behavior.

Insect cuticles that are mainly made of chitin, chitosan and proteins provide insects with rigid, stretchable and robust skins to defend harsh external environment. The insect cuticle therefore provides inspiration for engineering biomaterials with outstanding mechanical properties but also sustainability and biocompatibility. We herein propose a design of high-performance and sustainable bioplastics via introducing CPAP3-A1, a major structural protein in insect cuticles, to specifically bind to chitosan. Simply mixing 10w/w% bioengineered CPAP3-A1 protein with chitosan enables the formation of plastics-like, sustainably sourced chitosan/CPAP3-A1 composites with significantly enhanced strength (∼90 MPa) and toughness (∼20 MJ m -3), outperforming previous chitosan-based composites and most synthetic petroleum-based plastics. Remarkably, these bioplastics exhibit a stretch-strengthening behavior similar to the training living muscles. Mechanistic investigation reveals that the introduction of CPAP3-A1 induce chitosan chains to assemble into a more coarsened fibrous network with increased crystallinity and reinforcement effect, but also enable energy dissipation via reversible chitosan-protein interactions. Further uniaxial stretch facilitates network re-orientation and increases chitosan crystallinity and mechanical anisotropy, thereby resulting in stretch-strengthening behavior. In general, this study provides an insect-cuticle inspired design of high-performance bioplastics that may serve as sustainable and bio-friendly materials for a wide range of engineering and biomedical application potentials.

Organized assembly of chitosan into mechanically strong bio-composite by introducing a recombinant insect structural protein OfCPH-1.

Chitosan, known for its appealing biological properties in packaging and biomedical applications, faces challenges in achieving a well-organized crystalline structure for mechanical excellence under mild conditions. Herein, we propose a facile and mild bioengineering approach to induce organized assembly of amorphous chitosan into mechanically strong bio-composite via incorporating a genetically engineered insect structural protein, the cuticular protein hypothetical-1 from the Ostrinia furnacalis (OfCPH-1). OfCPH-1 exhibits high binding affinity to chitosan via hydrogen-bonding interactions. Simply mixing a small proportion (0.5 w/w%) of bioengineered OfCPH-1 protein with acidic chitosan precursor induces the amorphous chitosan chains to form fibrous networks with hydrated chitosan crystals, accompanied with a solution-to-gel transition. We deduce that the water shell destruction driven by strong protein-chitosan interactions, triggers the formation of well-organized crystalline chitosan, which therefore offers the chitosan with significantly enhanced swelling resistance, and strength and modulus that outperforms that of most reported chitosan-based materials as well as petroleum-based plastics. Moreover, the composite exhibits a stretch-strengthening behavior similar to the training living muscles on cyclic load. Our work provides a route for harnessing the OfCPH-1-chitosan interaction in order to form a high-performance, sustainably sourced bio-composite.

Enantioselective Tsuji-Trost α-Fluoroallylation of Amino Acid Esters with gem-Difluorinated Cyclopropanes.

A novel enantioselective Tsuji-Trost-type cross coupling reaction between gem-difluorinated cyclopropanes and N-unprotected amino acid esters enabled by synergistic Pd/Ni/chiral aldehyde catalysis is presented herein. This transformation streamlined the diversity-oriented synthesis (DOS) of optically active α-quaternary α-amino acid esters bearing a linear 2-fluoroallylic motif, which served as an appealing platform for the construction of other valuable enantioenriched compounds. The key intermediates were confirmed by HRMS detection, while DFT calculations revealed that the excellent enantioselectivity was attributed to the stabilizing non-covalent interactions between the Pd(II)-π-fluoroallyl species and the Ni(II)-Schiff base complex.

Coalescence-Induced Jumping of Nanodroplets in a Perpendicular Electric Field: A Molecular Dynamics Study.

Coalescence-induced jumping has promised a substantial reduction in the droplet detachment size and consequently shows great potential for heat-transfer enhancement in dropwise condensation. In this work, using molecular dynamics simulations, the evolution dynamics of the liquid bridge and the jumping velocity during coalescence-induced nanodroplet jumping under a perpendicular electric field are studied for the first time to further promote jumping. It is found that using a constant electric field, the jumping performance at the small intensity is weakened owing to the continuously decreased interfacial tension. There is a critical intensity above which the electric field can considerably enhance the stretching effect with a stronger liquid-bridge impact and, hence, improve the jumping performance. For canceling the inhibition effect of the interfacial tension under the condition of the weak electric field, a square-pulsed electric field with a paused electrical effect at the expansion stage of the liquid bridge is proposed and presents an efficient nanodroplet jumping even using the weak electric field.

Characterization of A π-π stacking cocrystal of 4-nitrophthalonitrile directed toward application in photocatalysis.

Photoexcitation of the electron-donor-acceptor complexes have been an effective approach to achieve radicals by triggering electron transfer. However, the catalytic version of electron-donor-acceptor complex photoactivation is quite underdeveloped comparing to the well-established utilization of electronically biased partners. In this work, we utilize 4-nitrophthalonitrile as an electron acceptor to facilitate the efficient π-stacking with electron-rich aromatics to form electron-donor-acceptor complex. The characterization and energy profiles on the cocrystal of 4-nitrophthalonitrile and 1,3,5-trimethoxybenzene disclose that the electron transfer is highly favorable under the light irradiation. This electron acceptor catalyst can be efficiently applied in the benzylic C-H bond photoactivation by developing the Giese reaction of alkylanisoles and the oxidation of the benzyl alcohols. A broad scope of electron-rich aromatics can be tolerated and a mechanism is also proposed. Moreover, the corresponding π-anion interaction of 4-nitrophthalonitrile with potassium formate can further facilitate the hydrocarboxylation of alkenes efficiently.

The microparticulate inks for bioprinting applications.

Three-dimensional (3D) bioprinting has emerged as a groundbreaking technology for fabricating intricate and functional tissue constructs. Central to this technology are the bioinks, which provide structural support and mimic the extracellular environment, which is crucial for cellular executive function. This review summarizes the latest developments in microparticulate inks for 3D bioprinting and presents their inherent challenges. We categorize micro-particulate materials, including polymeric microparticles, tissue-derived microparticles, and bioactive inorganic microparticles, and introduce the microparticle ink formulations, including granular microparticles inks consisting of densely packed microparticles and composite microparticle inks comprising microparticles and interstitial matrix. The formulations of these microparticle inks are also delved into highlighting their capabilities as modular entities in 3D bioprinting. Finally, existing challenges and prospective research trajectories for advancing the design of microparticle inks for bioprinting are discussed.

Multi-level chemical characterization and anti-inflammatory activity evaluation of the polysaccharides from Prunella vulgaris.

Prunella vulgaris (PV) is a medicine and food homologous plant, but its quality evaluation seldom relies on the polysaccharides (PVPs). In this work, we established the multi-level fingerprinting and in vitro anti-inflammatory evaluation approaches to characterize and compare the polysaccharides of P. vulgaris collected from the major production regions in China. PVPs prepared from 22 batches of samples gave the content variation of 5.76-24.524 mg/g, but displayed high similarity in the molecular weight distribution. Hydrolyzed oligosaccharides with degrees of polymerization 2-14 were characterized with different numbers of pentose and hexose by HILIC-MS. The tested 22 batches of oligosaccharides exhibited visible differences in peak abundance, which failed to corelate to their production regions. All the PVPs contained Gal, Xyl, and Ara, as the main monosaccharides. Eleven batches among the tested PVPs showed the significant inhibitory effects on NO production on LPS-induced RAW264.7 cells at 10 µg/mL, but the exerted efficacy did not exhibit correlation with the production regions. Conclusively, we, for the first time, investigated the chemical features of PVPs at three levels, and assessed the chemical and anti-inflammatory variations among the different regions of P. vulgaris samples.

Regio- and Enantioselective Synthesis of 1,2-Diamines by Formal Hydroamination of Enamines: Scope, Mechanism, and Asymmetric Synthesis of Orthogonally Protected Bis-Piperazines as a Privileged Scaffold.

We have previously reported the first formal hydroamination of enamines for the synthesis of chiral 1,2-diamines. Here, we describe: (i) the discovery, optimization, and substrate expansion of this reaction; (ii) a novel and straightforward protocol for the "click-type" synthesis of enamines in quantitative yield utilizing sodium sulfate in a dual role as an ancillary and dehydrating agent without the need for workup or purification; (iii) the application of this methodology to the first enantioselective synthesis of orthogonally protected 1,1'-(1-(4-fluorophenyl)ethane-1,2-diyl) piperazines, a scaffold for rapid lead optimization in drug discovery; (iv) a computational investigation into the mechanism and rationalization of the enantioselectivities of the reaction.

Benzyl Deuteriodifluoromethyl Sulfoxide: An Easily Accessible and Stable Reagent for Direct Deuterodifluoromethylthiolation.

A new, stable and scalable reagent based on a sulfoxide skeleton for direct deuteriodifluoromethylthiolation has been developed. The reagent displays excellent reactivities toward Tf2O promoted C-H deuteriodifluoromethylthiolation of electron-rich arenes, indoles, alkenes, and intramolecular lactonization of 2-alkynylbenzoates. Moreover, high deuteration rates and good to excellent yields were achieved under metal-free reaction conditions. As a result, a wide range of deuteriodifluoromethylthilolated compounds were prepared, enabling further applications in drug discovery.

Spatial-temporal shifting patterns and in situ conservation of spotted seal (Phoca largha) populations in the Yellow Sea ecoregion.

Understanding the habitat shifting pattern is a prerequisite for implementing in situ conservation of migratory species. Spotted seals (Phoca largha) inhabiting the Yellow Sea ecoregion (YSE) comprise a small population with independent genes and represent a charismatic flagship species in this region. However, this population has declined by 80% since the 1940s, and increased support from the countries around the YSE is urgently needed to address the potential local extinction risk. A time-series niche model and life-history weighted systematic conservation planning were designed on the basis of a satellite beacon tracking survey (2010-2020) of the YSE population. The results showed clustering and spreading shifting patterns during the breeding and migratory seasons, respectively. The closed-loop migration route formed in the YSE indicated that this population might be geographically isolated from populations in other breeding areas around the world. The conservation priority area (CPA), with an area of 19 632 km2 (3.58% of the total YSE area), was the most effective response to the potential in situ risk. However, nearly 80% of the CPA was exposed outside the existing marine protected areas (MPAs). Future establishment of MPAs in China should strategically consider the conservation gap identified herein, and it is recommended for Korea's closed fishing season to be spatially set in the western Korean Peninsula from May to August. This study also exemplified that the lack of temporal information would lead to the dislocation of niche modeling for migratory species represented by spotted seals. Attention should be paid to protecting small and migratory populations in marine biodiversity conservation planning.

Madecassoside alleviates acute kidney injury by regulating JNK-mediated oxidative stress and programmed cell death.

BACKGROUND: Acute kidney injury (AKI) has high morbidity and mortality, which is manifested by inflammation and apoptosis. Effective treatment methods for AKI are currently lacking. OBJECTIVE: This study demonstrated the protecting effects of Madecassoside (MA) in the cisplatin- and hypoxia-reoxygenation-induced renal tubular epithelial cells in vitro and AKI mice in vivo. METHODS: In vivo AKI mouse models were established by inducing them with cisplatin and renal ischemia-reperfusion. In vitro injury models of mouse renal tubular epithelial cells were established by inducing them with cisplatin and hypoxia and reoxygenation, respectively. The mechanism of MA effects was further explored using molecular docking and RNA-sequencing. RESULTS: MA could significantly reduce kidney injury in the cisplatin-and renal ischemia-reperfusion (IRI)-induced AKI. Further validation in the two cellular models also showed that MA had protect effects. MA can alleviate AKI in vitro and in vivo by inhibiting inflammation, cell apoptosis, and oxidative stress. MA exhibited high permeability across the Caco-2 cell, can enter cells directly. Through RNA-seq and molecular docking analysis, this study further demonstrated that MA inhibits its activity by directly binding to JNK kinase, thereby inhibiting c-JUN mediated cell apoptosis and improving AKI. In addition, MA has better renal protective effects compared to curcumin and JNK inhibitor SP600125. CONCLUSION: The results demonstrate that MA might be a potential drug for the treatment of AKI and act through the JNK/c-JUN signaling pathway.

Enantioselective Palladium(II)-Catalyzed Desymmetrizative Coupling of 7-Azabenzonorbornadienes with Alkynylanilines.

A PdII -catalyzed, domino enantioselective desymmetrizative coupling of 7-azabenzonorbornadienes with alkynylanilines is disclosed herein. This operationally simple transformation generates three covalent bonds and two contiguous stereocenters with excellent enantio- and diastereo-selectivity. The resulting functionalized indole-dihydronaphthalene-amine conjugates served as an appealing platform to streamline the diversity-oriented synthesis (DOS) of other valuable enantioenriched compounds. DFT calculations revealed that the two stabilizing non-covalent interactions contributed to the observed enantioselectivity.

Heterometallic AuI 6 AgI 6 Macrocyclic Cluster Templated by a Supramolecular Melamine Dimer.

The application of supramolecular templates in aligning atomically precise heterometal arrays is important for pursuing functional materials. Herein, we report that a bilayered supramolecular tri-deprotonated melamine dimer functions as an effective template in the construction of a heterometallic gold(I)-silver(I) macrocyclic cluster [µ6 -(C3 N6 H3 )3- ]2 -AuI 6 AgI 6 . X-ray single crystal structural analysis showed that a crown-like AuI 6 AgI 6 macrocycle is aligned around two parallelly stacked µ6 -(C3 N6 H3 )3- moieties hold together with π-π interactions. Theoretical calculations revealed that the [µ6 -(C3 N6 H3 )3- ]2 motif dominantly contributes to the near-occupied orbitals in the electronic structure, which is closely related to its luminescence properties. This work demonstrates that the supramolecular templates containing multiple symmetric binding sites may present a facile approach in the construction of functional metal clusters.