Immunomodulatory effects of calcium phosphate microspheres: influences of particle size on macrophage polarization and secretion patterns.

This study investigated the immunomodulatory effects of calcium phosphate (CaP) microspheres, focusing on how particle size influenced macrophage polarization and cytokine secretion patterns. SEM analysis revealed that HA microspheres predominantly exhibited a spherical shape with distinct sizes and sub-micro-sized pores. The average particle sizes for the S1, S2, and S3 groups were 17.

Collagen-based hydrogels induce hyaline cartilage regeneration by immunomodulation and homeostasis maintenance.

Type I collagen (Col I) and hyaluronic acid (HA), derived from the extracellular matrix (ECM), have found widespread application in cartilage tissue engineering. Nevertheless, the potential of cell-free collagen-based scaffolds to induce in situ hyaline cartilage regeneration and the related mechanisms remain undisclosed. Here, we chose Col I and HA to construct Col I hydrogel and Col I-HA composite hydrogel with similar mechanical properties, denoted as Col and ColHA, respectively.

Phytopathogenic Fungicidal Activity and Mechanism Approach of Three Kinds of Triphenylphosphonium Salts.

The triphenylphosphonium (TPP) cation has been widely used as a carrier for mitochondria-targeting molecules. We synthesized two commonly employed targeting systems, namely, ω-triphenylphosphonium fatty acids (group 2) and ω-triphenylphosphonium fatty alcohols (group 3), to assess the impact of the TPP module on the biological efficacy of mitochondria-targeting molecules. We evaluated their fungicidal activities against nine plant pathogenic fungi in comparison to alkyl-1-triphenylphosphonium compounds (group 1).

Structure driven bio-responsive ability of injectable nanocomposite hydrogels for efficient bone regeneration.

Injectable hydrogels are promising for treatment of bone defects in clinic owing to their minimally invasive procedure. Currently, there is limited emphasis on how to utilize injectable hydrogels to mobilize body's regenerative potential for enhancing bone regeneration. Herein, an injectable bone-mimicking hydrogel (BMH) scaffold assembled from nanocomposite microgel building blocks was developed, in which a highly interconnected microporous structure and an inorganic/organic (methacrylated hydroxyapatite and methacrylated gelatin) interweaved nano structure were well-designed.

Effects of an Early Intensive Blood Pressure-lowering Strategy Using Remifentanil and Dexmedetomidine in Patients with Spontaneous Intracerebral Hemorrhage: A Multicenter, Prospective, Superiority, Randomized Controlled Trial.

Background: Although it has been established that elevated blood pressure and its variability worsen outcomes in spontaneous intracerebral hemorrhage, antihypertensives use during the acute phase still lacks robust evidence. A blood pressure-lowering regimen using remifentanil and dexmedetomidine might be a reasonable therapeutic option given their analgesic and antisympathetic effects. The objective of this superiority trial was to validate the efficacy and safety of this blood pressure-lowering strategy that uses remifentanil and dexmedetomidine in patients with acute intracerebral hemorrhage.

Synthesis and Biological Activities of Novel Pyrazole Carboxamides Containing an Aryloxypyridyl Ethylamine Module.

Pyrazole carboxamide is widely utilized in agricultural crop protection. In this research, we synthesized two classes of compounds, namely, pyrazole-5-carboxamide () and pyrazole-4-carboxamide (), which are distinguished by the inclusion of the -1-(6-aryloxypyridin-3-yl) ethylamine skeleton. This design was inspired by the frequent occurrence of diaryl ether modules in pesticide molecules.

4-Vinylbenzodioxinones as a new type of precursor for palladium-catalyzed (4+3) cycloaddition of azomethine imines.

In this paper, benzo-fused cyclic carbonates were designed and synthesized as a new type of precursor of π-allylpalladium zwitterionic intermediates, and were applied in Pd-catalyzed diastereo- and enantioselective (4+3) cycloaddition with ,-cyclic azomethine imines, leading to various biologically important 1,3,4-benzoxadiazepine derivatives in 43-99% yields with 6 : 1 to >20 : 1 dr and up to 95% ee.

Diastereoselective Synthesis of Allenes through Phosphine-Catalyzed Cascade Isomerization/Annulation.

Phosphine-catalyzed cascade isomerization/annulation has been developed to realize a diastereoselective synthesis of allenes installed on the hexahydropentalene skeleton, which contains five chiral centers (and one axial chirality). This reaction tolerated a broad range of allenoates and enynes. The allene products were transformed to various halogen-substituted fused-ring compounds.

Nanohybrid dual-network chitosan-based hydrogels: Synthesis, characterization, quicken infected wound healing by angiogenesis and immune-microenvironment regulation.

Infectious wounds are difficult to heal because of vascular damage and immune imbalance. The multi-functional hydrogel dressing can regulate vascular regeneration and immune microenvironment through continuous supply of bioactive ingredients to the wound site, which can effectively accelerate the healing speed of infected wounds. In this work, a multifunctional dual-network hydrogel (QCMOD) with good injectability, stability, self-healing and adhesion was designed by combining methacrylic anhydride-modified quaternized chitosan (QCM) with oxidized dextran (OD) via Schiff base reaction and photo-crosslinked polymerization.

Synthesis and Antiphytopathogenic Activity of Novel Oxazolidine-2,4-diones Bearing Phenoxypyridine Moiety.

In the present study, we conducted optimization of pyramoxadone and synthesized a series of novel oxazolidinediones. Antifungal assays showed that these compounds exhibited moderate to excellent antifungal activity against various pathogens. Further SAR analysis revealed that the introduction of substituents to the benzene ring of the phenoxy group or the inclusion of bulky groups, such as -butyl, on the aniline moiety, had a detrimental effect on the activity.

Functional injectable hydrogel with spatiotemporal sequential release for recruitment of endogenous stem cells and cartilage regeneration.

Articular cartilage is refractory to self-healing due to the absence of vascular, nervous, and lymphatic systems, and its repair remains a clinical challenge. Tissue regeneration through recruitment of stem cells cell-free scaffolds is a promising alternative strategy. Herein, a kind of functional injectable hydrogel system (Col-Apt@KGN MPs), which is a collagen-based and microsphere-embedded cell-free scaffold, was designed to achieve spatiotemporal regulation of endogenous mesenchymal stem cells (MSCs) recruitment and their chondrogenic differentiation by respective release of aptamer 19S (Apt19S) and kartogenin (KGN).

Discovery of triphenylphosphonium (TPP)-conjugated N-(1,1'-biphenyl)-2-yl aliphatic amides as excellent fungicidal candidates.

Background: Succinate dehydrogenase inhibitors (SDHIs) are the fastest growing agricultural fungicides at present, but their rapidly growing resistance is a serious problem for their application. Previously, we screened out a fungicidal lead compound CBUA-TPP (1) through triphenylphosphonium (TPP)-driven mitochondrial-targeting strategy. The targeting led to the rapid accumulation of 1 in mitochondria and the saturation inhibition of complex II in a short time, resulting in electron leakage and the explosion of reactive oxygen species (ROS).

Strategies of strengthening mechanical properties in the osteoinductive calcium phosphate bioceramics.

Calcium phosphate (CaP) bioceramics are widely applied in the bone repairing field attributing to their excellent biological properties, especially osteoinductivity. However, their applications in load-bearing or segmental bone defects are severely restricted by the poor mechanical properties. It is generally considered that it is challenging to improve mechanical and biological properties of CaP bioceramics simultaneously.

Triphenylphosphonium-Driven Targeting of Pyrimorph Fragment Derivatives Greatly Improved Its Action on Phytopathogen Mitochondria.

Pyrimorph is a carboxylic acid amide (CAA) fungicide, which shows excellent activity against oomycetes such as pepper , , and downy mildew of cucumber. It works mainly by inhibiting the biosynthesis of cell wall of oomycetes. However, pyrimorph also shows weak activity of inhibiting mitochondrial complex III, which is the first CAA fungicide found to act on mitochondria.

Design, synthesis, and insecticidal activity of a novel series of flupyrimin analogs bearing 1-aryl-1H-pyrazol-4-yl subunits.

To discover new potential insecticides to protect agricultural crops from damage, a series of novel flupyrimin derivatives containing an arylpyrazole core were designed and synthesized. Their structures were confirmed by H NMR, C NMR, and HRMS. Bioassays indicated that the 31 compounds synthesized possessed excellent insecticidal activity against .

Mitochondrion-Targeted Triphenylphosphonium-Based Kresoxim-Methyl Analogues: Synthesis, Fungicidal Activity, and Action Mechanism Approach.

β-Methoxyacrylate fungicides as complex III Q site inhibitors play a crucial role in the control of crop diseases. In this study, the triphenylphosphonium (TPP)-driven mitochondrion-targeting strategy was used to modify the kresoxim-methyl scaffold at the toxicophore or side chain to develop novel mitochondrion-targeted QI fungicides. These kresoxim-methyl analogues exhibited different fungicidal activities, depending on the position of TPP conjugation and the linker length.

Enhanced ectopic bone formation by strontium-substituted calcium phosphate ceramics through regulation of osteoclastogenesis and osteoblastogenesis.

To explore how strontium influences osteoclastogenesis and osteoblastogenesis during material-induced ectopic bone formation, porous strontium-substituted biphasic calcium phosphate (Sr-BCP) and BCP ceramics with equivalent pore structures and comparable grain size and porosity were prepared. results showed that compared with BCP, Sr-BCP inhibited the osteoclastic differentiation of osteoclast precursors by delaying cell fusion, down-regulating the expression of osteoclast marker genes, and reducing the activity of osteoclast specific proteins, possibly due to the activated ERK signaling pathway but the suppressed p38, JNK and AKT signaling pathways. Meanwhile, Sr-BCP promoted the osteogenic differentiation of mesenchymal stem cells (MSCs) by up-regulating the osteogenic gene expression.

Ventilator-associated pneumonia prevention in the Intensive care unit using Postpyloric tube feeding in China (VIP study): study protocol for a randomized controlled trial.

Background: Ventilator-associated pneumonia is a challenge in critical care and is associated with high mortality and morbidity. Although some consensuses on preventing ventilator-associated pneumonia are reached, it is still somewhat controversial. Meta-analysis has shown that postpyloric tube feeding may reduce the incidences of ventilator-associated pneumonia, which still desires high-quality evidence.

Pd-Catalyzed [4 + 2] cycloaddition of methylene cyclic carbamates with dihydropyrazolone-derived alkenes: synthesis of spiropyrazolones.

In this paper, a palladium-catalyzed [4 + 2] cycloaddition of 5-methylene-1,3-oxazinan-2-ones with 4-arylidene-2,4-dihydro-3-pyrazol-3-ones has been developed to produce spiropyrazolones in high yields with excellent diastereoselectivities in nearly all cases. The cycloaddition reaction was scaled-up without significant loss of yield, and its synthetic utility has been demonstrated by further transformations of the products. The reaction type of N-Ts cyclic carbamates under palladium catalysis was extended to include [4 + 2] cycloaddition for the first time.

Autologous Cytokine-Induced Killer Cell Immunotherapy Enhances Chemotherapy Efficacy against Multidrug-Resistant Tuberculosis.

Objective: Multidrug-resistant tuberculosis (MDR-TB) causes persistent infection and challenges tuberculosis control worldwide. T cell-mediated immunity plays a critical role in controlling (Mtb) infection, and therefore, enhancing Mtb-specific T cell immune responses represents a promising therapeutic strategy against TB. Cytokine-induced killer (CIK) immunotherapy is based on autologous infusion of in vitro expanded bulk T cells, which include both pathogen-specific and nonspecific T cells from patient peripheral blood mononuclear cells (PBMC) into TB patients.

A chitosan-based multifunctional hydrogel containing rapidly bioreduced silver nanoparticles for accelerating infected wound healing.

Generally, bacterial infection seriously hinders the wound healing process, so it is crucial to safeguard the wound from severe infection. Besides, multifunctional hydrogel dressings (self-healing, injectable, antibacterial and adaptable) seem to be conducive to meet the needs of wound healing. Here, a double-crosslinked multifunctional hydrogel (COC hydrogel) based on quaternized chitosan, methacrylate anhydride-modified collagen and oxidized dextran was developed.

Enhanced bone regenerative properties of calcium phosphate ceramic granules in rabbit posterolateral spinal fusion through a reduction of grain size.

Osteoinductivity is a crucial factor to determine the success and efficiency of posterolateral spinal fusion (PLF) by employing calcium phosphate (Ca-P) bioceramics. In this study, three kinds of Ca-P ceramics with microscale to nanoscale gain size (BCP-control, BCP-micro and BCP-nano) were prepared and their physicochemical properties were characterized. BCP-nano had the spherical shape and nanoscale gain size, BCP-micro had the spherical shape and microscale gain size, and BCP-control (BAM®) had the irregular shape and microscale gain size.