A Reactive Oxygen Species "Sweeper" Based on Hollow Mesopore Cerium Oxide Nanospheres for Targeted and Anti-Inflammatory Management of Osteoarthritis.

Osteoarthritis (OA) is a progressive joint disorder characterized by sustained oxidative stress, chronic inflammation, and the degradation of cartilage. Despite extensive research on nanocarrier treatment strategies, the therapeutic efficacy remains limited due to the lack of satisfactory vehicles that can simultaneously exhibit excellent ROS scavenging capabilities and high drug loading capacity for effective nonsurgical management of OA. In this work, we propose an innovative strategy utilizing hollow mesoporous cerium oxide nanospheres coated with membranes derived from apoptotic chondrocytes as a reactive oxygen species "sweeper" for targeted and anti-inflammatory therapy of OA. The developed DEX@HMCeNs@M demonstrates superior drug loading capacity, notable antioxidant properties, favorable biocompatibility, and controlled drug release. By leveraging the camouflage provided by apoptotic chondrocyte membranes, the engineered DEX@HMCeNs@M, which bear natural "eat me" signals, can effectively mimic chondrocyte apoptotic bodies within the joints, thereby enabling targeted delivery of the anti-inflammatory drug DEX and subsequent controlled release triggered by the acidic environment of OA. Both in vitro and in vivo experiments validate the enhanced therapeutic efficacy of our DEX@HMCeNs@M sweeper, which operates through a synergistic mechanism involving scavenging of ROS overproduction, inhibition of inflammation, restoration of mitochondrial damage, and reduction of chondrocyte apoptosis. These findings underscore the potential and efficiency of our developed DEX@HMCeNs@M strategy as an encouraging interventional approach for the progressive treatment of OA.

The potential therapeutic value and application prospect of engineered exosomes in human diseases.

Exosomes are tiny vesicles produced by a wide range of cells that contain complex RNA and protein. In the diagnosis, treatment, and prevention of illness, they offer great potential. In vitro engineering technique modifies exosomes to produce designed exosomes that include nucleic acids, proteins, and medicines, and are targeted to particular tissues or cells. Their applications range from tumor imaging and gene therapy to vaccine production and regenerative medicine to targeted medication delivery. Many disciplines have promising futures for using this technology. In this review, we'll look at the potential therapeutic usefulness and use of engineered exosomes in a variety of human illnesses with various systemic manifestations.

GTPBP4: A New Therapeutic Target Gene Promotes Tumor Progression in Non-Small Cell Lung Cancer via EMT.

Lung cancer has a complex etiology involving multiple regulatory systems. Uncertainty about the biology and evolution of lung cancer has made it difficult to improve its poor prognosis. To create efficient therapeutic targets and optimal molecular screening tools for lung cancer, the most important task seems to be to understand how it develops and progresses. The expression and regulation of GTPBP4 in non-small cell lung cancer (NSCLC) are not well understood. Using methods such as knocking down GTPBP4 in lung cancer cells and establishing a mouse lung cancer model, we found that the expression of GTPBP4 was upregulated in human lung adenocarcinoma cells and tissues, and that knocking down the expression of the GTPBP4 gene in A549 and Calu-1 lung adenocarcinoma cells can inhibit the proliferation of lung adenocarcinoma cells and reduce their invasion ability. The results of the mouse lung cancer model showed that the lung weight and the number of lung surface nodules decreased significantly in the LLC-GTPBP4 KO group. The mechanism by which GTPBP4 regulation affects the progression of lung adenocarcinoma may be related to the regulation of EMT. From this study, new research ideas emerge to explore GTPBP4 as a biomarker and therapeutic target for early diagnosis and treatment of lung cancer.

Double-Decker-Shaped Polyhedral Silsesquioxanes Reinforced Epoxy/Bismaleimide Hybrids Featuring High Thermal Stability.

In this study, we synthesized bismaleimide into a functionalized double-decker silsesquioxane (DDSQ) cage. This was achieved by hydrosilylation of DDSQ with nadic anhydride (ND), reacting it with excess p-phenylenediamine to obtain DDSQ-ND-NH2, and treating with maleic anhydride (MA), which finally created a DDSQ-BMI cage structure. We observed that the thermal decomposition temperature (Td) and char yield were both increased upon increasing the thermal polymerization temperature, and that these two values were both significantly higher than pure BMI without the DDSQ cage structure since the inorganic DDSQ nanoparticle could strongly enhance the thermal stability based on the nano-reinforcement effect. Based on FTIR, TGA, and DMA analyses, it was found that blending epoxy resin with the DDSQ-BMI cage to form epoxy/DDSQ-BMI hybrids could also enhance the thermal and mechanical properties of epoxy resin due to the organic/inorganic network formation created by the ring-opening polymerization of the epoxy group and the addition polymerization of the BMI group due to the combination of the inorganic DDSQ cage structure and hydrogen bonding effect. The epoxy/DDSQ-BMI = 1/1 hybrid system displayed high Tg value (188 °C), Td value (397 °C), and char yield (40.4 wt%), which was much higher than that of the typical DGEBA type epoxy resin with various organic curing agents.

[Experimental study on reconstruction of anterior labrum of shoulder joint by chemical extraction of allogeneic tendon and allogeneic chondrocytes].

OBJECTIVE: To study the effect of chemical extraction of allogeneic tendon and allogeneic chondrocytes for reconstruction of anterior labrum of shoulder joint in rabbits. METHODS: The body weight of 45 adult New Zealand white rabbits ranged from 2.5 to 3.0 kg. The Achilles tendons of 15 rabbits were taken and the allogeneic tendons were prepared by chemical extraction with antigen inactivation. The extracted tendons were compared with untreated tendons by HE and Masson stainings. Chondrocytes were isolated and cultured by trypsin method and identified by immunohistochemical staining of collagen type Ⅱ. The remaining 30 rabbits were used to prepare the model of anterior labrum defect of shoulder joint. After the allogeneic tendon was transplanted to the damaged labrum, the rabbits was randomly divided into two groups (15 in each group). In group A, the allogeneic chondrocytes were injected into the joint immediately after transplantation, while in group B, no treatment was made. At 4, 6, and 8 weeks after operation, 5 transplanted tendons of each group were taken. After general observation, HE staining was used to observe the number of nuclei, Masson staining was used to observe the expression of collagen fibers in muscle fiber tissues, and AB staining was used to detect the glycosaminoglycan level after transplantation, to evaluate the cell growth in the tissues of the two groups of allogeneic tendon. RESULTS: By HE and Masson stainings, the allogeneic tendon antigen prepared by chemical extraction method was inactivated and the fibrous tissue structure was intact; collagen type Ⅱ immunohisto-chemistry staining showed that the cultured cells were chondrocytes. After tendon transplantation, the content of glycosaminoglycan in group A was significantly higher than that in group B ( P<0.05). At 6 weeks after operation, HE staining showed that the nuclear in tendon tissue of group A was significantly more than that of group B ( t=20.043, P=0.000). Masson staining showed that the number of nuclei in tendon tissue of group A was significantly increased, the muscle fibers and collagen fibers were interlaced, the tissue structure was more compact, and the tendon tissue was mainly blue stained; while the number of nuclei in group B was less, mainly collagen fibers of the original graft. CONCLUSION: The allogeneic tendon inactivated by chemical extraction can be used to reconstruct the defect of anterior labrum of shoulder joint in rabbits, and the combination of allogeneic chondrocytes can promote the healing of tendon transplantation.

Allogenic Tendon-Autologous Cartilage Cells Transplantation Enhances Adhesive/Growth Ability and Promotes Chondrogenesis in a Rabbit Model of Glenoid Labrum Damage.

BACKGROUND Glenoid labrum injury of the shoulder commonly occurs in athletes, especially those who perform throwing motions. This study investigated the effects of the established allogenic tendon-autologous cartilage cells reconstruction approach in a rabbit model of glenoid labrum damage. MATERIAL AND METHODS The allogenic tendons were isolated and extracted using the chemical extraction method. Cartilage cells were isolated from New Zealand rabbits and identified by detecting type II collagenase. The allogenic tendon-autologous cartilage cells were transplanted to the damaged glenoid labrum. HE staining was used to observe inflammatory cells, Masson staining was used to observe muscle fibers, and scanning electron microscopy (SEM) was used to assess antigenicity of tendon tissues. PSA and AB staining were used to examine neutral protein mucopolysaccharide and acidic protein mucopolysaccharide, respectively. We assessed cartilage cell growth in autologous cartilage cells combined with allogenic tendon transplanted tissues. RESULTS Allogenic tendons were well prepared using chemical extraction method due to use of HE staining, Masson staining, and SEM. TGF-ß1 treatment induced cartilage cell formation and triggered expression of acidic and neutral protein mucopolysaccharides. HE staining, Masson staining, PAS staining, and AB staining methods showed that autologous cartilage cells combined with allogenic tendon transplanted tissues had better growth of cartilage cells. CONCLUSIONS This study establishes the allogenic tendon-autologous cartilage cells reconstruction and transplantation approach and illustrated higher adhesive ability and growth ability, and better chondrogenesis in a rabbit model of glenoid labrum damage.

The application of BMP-12-overexpressing mesenchymal stem cells loaded 3D-printed PLGA scaffolds in rabbit rotator cuff repair.

This study investigates if the application of bone marrow-derived mesenchymal stem cells (BM-MSCs) loaded 3D-printed scaffolds could improve rotator cuff repair. The polylactic-co-glycolic acid (PLGA) scaffolds were fabricated by 3D print technology. Rabbit BM-MSCs were transfected with a recombinant adenovirus encoding bone morphogenic protein 12 (BMP-12). The effect of BM-MSCs loaded PLGA scaffolds on tendon-bone healing was assessed by biomechanical testing and histological analysis in a rabbit rotator cuff repair model. We found that the PLGA scaffolds had good biocompatible and biodegradable property. Overexpression of BMP-12 increased the mRNA and protein expression of tenogenic genes in BM-MSCs cultured with DMEM medium and seeded in PLGA scaffolds. When BMP-12-overexpressing BM-MSCs-loaded PLGA scaffolds were implanted into the injured rabbit supraspinatus tendon-bone junctions, the tendon-bone healing was improved. Our results suggest that application of BMP-12 overexpressing BM-MSCs loaded 3D-printed PLGA scaffolds promote the healing of tendon-bone interface, improve collagen organization and increase fibrocartilage in the rabbit rotor cuff repair. Rotator cuff regeneration achieved by BMP-12-overexpressing BM-MSCs-loaded PLGA scaffolds may represent a novel approach for the management of rotator cuff defect.

Double-bundle revision anterior cruciate ligament reconstruction is effective in rescuing failed primary reconstruction and re-introducing patients to physical exercise.

The anterior cruciate ligament (ACL) is one of a pair of cruciate ligaments in the human knee and is critical for knee stability, as it limits anterior tibial translation on the femur, restrains rotation and resists varus and valgus joint forces. The present study aimed to assess the effect of double-bundle revision anterior cruciate ligament (ACL) reconstruction in improving the subjective and objective functions and re-introducing patients to physical activity after primary ACL reconstruction had failed. A total of 34 patients who underwent double-bundle ACL revision surgeries were included in the present retrospective study. Lysholm, Tegner and IKDC scores as well as KT-2000 arthrometry measures were obtained pre- and post-operatively. The follow-up time was at least 2 years. The results indicated that the IKDC, Lysholm and Tegner scores as well as KT-2000 flexion scores were significantly improved after revision ACL reconstruction. All patients resumed to performing physical exercise activities after revision surgeries, 65% of whom reached pre-injury levels. In conclusion, these results demonstrated that double-bundle revision ACL reconstruction was consistently effective in rescuing failed primary ACL reconstruction and re-introducing patients to physical exercise.

Melt-Processable Semicrystalline Polyimides Based on 1,4-Bis(3,4-dicarboxyphenoxy)benzene Dianhydride (HQDPA): Synthesis, Crystallization, and Melting Behavior.

It is a great challenge to develop semicrystalline polyimides exhibited significant recrystallization ability and fast crystallization kinetics from the melt. A series of semicrystalline polyimides based on 1,4-bis(3,4-dicarboxyphenoxy)benzene dianhydride (HQDPA) and different diamines, including 1,3-bis(4-aminophenoxy)benzene (TPER), 1,4-bis(4-aminophenoxy)benzene (TPEQ), 4,4'-oxydianiline (4,4'-ODA) and 4,4'-bis(4-aminophenoxy)biphenyl (BAPB), end capped with phthalic anhydride were synthesized. Crystallization and melting behaviors were investigated by differential scanning calorimetry (DSC). The polyimide derived from HQDPA/TPER (PI-1) exhibited a glass transition temperature (Tg) at 190 °C and double melting temperatures (Tms) at 331 °C and 350 °C, and the polyimide derived from HQDPA/TPEQ (PI-2) displayed a Tg at 214 °C and a Tm at 388 °C. PI-1 and PI-2 showed significant recrystallization ability from melt and high crystallization rate by isothermal crystallization kinetics study, while polyimides based on 4,4'-ODA and BAPB lost crystallizability once taken to the melt. These polyimides also exhibited excellent thermo-oxidative stability with 5% weight loss temperature higher than 500 °C and good mechanical properties with tensile moduli of 2.0⁻3.3 GPa, tensile strengths of 85⁻105 MPa and elongations at break of 5⁻18%. PI-1 also possessed outstanding melt flowability with less than 300 Pa·s around 370 °C by rheological measurements.

[SPECIFIC DIAGNOSTIC SIGNIFICANCE OF "RIPPLE SIGN" OF MEDIAL FEMORAL CONDYLE UNDER ARTHROSCOPE IN MEDIAL LONGITUDINAL MENISCAL TEARS].

OBJECTIVE: To investigate the reliability of the "ripple sign" on the upper surface of the medial femoral condyle in the diagnosis of medial longitudinal meniscal tears under arthroscope. METHODS: Between June 2013 and June 2014, 56 patients with knee injuries were included. There were 35 males and 21 females with an average age of 22.2 years (range, 12-38 years). The causes of injury were sports in 40 cases, falling in 10 cases, and traffic accident in 6 cases. The injury was located at the left knee in 22 cases and at the right knee in 34 cases. The disease duration was 10-40 days (mean, 20.2 days). Of 56 patients, 15 cases had simple medial meniscal injury; 41 cases had combined injuries, including anterior cruciate ligament injury in 38 cases, posterior cruciate ligament injury in 2 cases, and patellar dislocation in 1 case. The "ripple sign" was observed under arthroscope before operation. Repair of medial meniscal injury and reconstruction of cruciate ligament were performed. RESULTS: The positive "ripple sign" was seen under arthroscope in all patients, who were diagnosed to have longitudinal meniscal tears, including 23 cases of mild "ripple sign" , 28 cases of moderate "ripple sign", and 5 cases of severe "ripple sign". CONCLUSION: The "ripple sign" on the upper surface of the medial femoral condyle is a reliable diagnostic evidence of medial longitudinal meniscal tears.

Highly thermostable, flexible, transparent, and conductive films on polyimide substrate with an AZO/AgNW/AZO structure.

Flexible transparent conductive films (TCFs) are used in a variety of optoelectronic devices. However, their use is limited due to poor thermostability. We report hybrid TCFs incorporation in both aluminum-doped zinc oxide (AZO) and silver nanowires (AgNWs). The layered AZO/AgNWs/AZO structure was deposited onto a transparent polyimide (PI) substrate and displayed excellent thermostability. When heated to 250 °C for 1 h, the change in resistivity (Rc) was less than 10% (Rc of pure AgNW film > 500) while retaining good photoelectric properties (Rsh = 8.6 Ohm/sq and T = 74.4%). Layering the AgNW network between AZO films decreased the surface roughness (Rrms < 8 nm) and enhances the mechanical flexibility of the hybrid films. The combination of these characteristics makes the hybrid film an excellent candidate for substrates of novel flexible optoelectronic devices which require high-temperature processing.

Modeling of material orientation effects on AHSS crush and fracture behavior in axial crush tests.

OBJECTIVE: Due to the rolling manufacturing process, most advanced high-strength steels (AHSS) demonstrate in-plane anisotropic material behavior. This study investigates the effects of material orientation on the axial crush behavior and fracture of AHSS with axial crush tests and computer simulations. METHODS: Crush simulation models considering material anisotropy and damage evolution were developed in LS-DYNA based on the drop-tower crush test results and coupon characterization test data for DP780 steel. The modified Mohr-Coulomb (MMC) isotropic fracture model was employed in the crush simulation models for fracture prediction. RESULTS: The 12-sided components fabricated in the transverse (T) direction of the sheet exhibited slightly higher crush loads and reduced crush distances compared to those in the longitudinal (L) direction. The crush behavior in each direction was generally proportional to ultimate tensile strength. All of the materials investigated in this study showed some cracking in the crush tests for both component orientations, but only DP780 showed significant anisotropy in fracture behavior with more cracking for the T direction compared to the L direction. Overall, the amount of cracking observed in the tests had little or no significant effect on the axial crush performance. The MMC fracture loci in both the L and T directions were determined using a reverse engineering approach, and the stress-strain curves beyond the uniform elongation point were extended using an optimization method. Both material models MAT103 and MAT224 predicted the crush and fracture behavior with reasonably good accuracy. CONCLUSIONS: The predicted fracture mode and force-displacement curves agreed well with the test data for both the L and T directions in axial crush tests of the 12-sided components. The simple isotropic material model MAT224 is adequate for crush simulations to predict material orientation effects on AHSS component crush performance and fracture behavior.

A novel synthesis of oxazolidine-2,4-diones via an efficient fixation of CO2 with 3-aryl-2-alkynamides.

A very mild protocol for fixation of carbon dioxide with 2-alkynamides in DMSO at 30 °C using a CO(2) balloon in the presence of K(2)CO(3) has been developed, which leads to an efficient assembly of oxazolidine-2,4-diones. It is observed that the regioselectivity was controlled by the aryl group.

Magneto-structural relationships for radical cation and neutral pyridinophane structures with intrabridgehead nitrogen atoms. An integrated experimental and quantum mechanical study.

An integrated experimental and computational approach was used to compare the properties of representative molecules containing intrabridgehead nitrogen atoms with those of the corresponding radical cations issuing from one-electron oxidation with the aim of unraveling the characteristics of the three-electron sigma-bonds formed in the open-shell species. From a quantitative point of view, last-generation density functional methods coupled with proper basis sets and, when needed, continuum models for describing bulk solvent effects confirm their reliability for the computation of structures and magnetic properties of organic free radicals. From an interpretative point of view, different hybridizations of nitrogen atoms tuned by their chemical environment lead to markedly different magnetic properties that represent reliable and sensitive probes of structural and electronic characteristics.

A novel synthesis of 1,3-oxazine-2,4-diones via a simple and efficient reaction of CO2 with 2,3-allenamides.

A simple and efficient reaction of CO(2) with 2,3-allenamides under mild conditions (CO(2) balloon without any metal catalyst in the presence of K(2)CO(3) or Cs(2)CO(3)) leads to an efficient synthesis of 1,3-oxazine-2,4-diones. The high reactivity of the allene moiety is crucial for the success of this transformation since the corresponding reaction of alpha,beta-unsaturated alkenamides or alkynamides does not occur.

PtCl4-catalyzed cyclization reaction of beta-allenols in the presence of indoles.

The highly regioselective PtCl4-catalyzed reaction of indoles with beta-allenols in THF at room temperature afforded indole derivatives containing a six-membered ether ring at the 3-position in moderate isolated yields. On the basis of a D-labeling experiment, a mechanistic rationale was proposed.

Pd(OAc)2-catalyzed cyclization of 2,3-allenoic acids in the presence of terminal alpha,beta-unsaturated alkynones: a one-pot highly stereoselective synthesis of 4-(3'-oxo-1'(E)-alkenyl)-2(5H)-furanones.

The Pd(OAc) 2-catalyzed cyclization reaction of 2,3-allenoic acids in the presence of terminal alpha,beta-unsaturated alkynones afforded an E/ Z mixture of 4-(3'-oxo-1'-alkenyl)-2(5 H)-furanones. A subsequent complete isomerization of the Z-isomer to E-isomer was observed in DMSO at 90 degrees C, which led to a highly stereoselective synthesis of 4-(3'-oxo-1'( E)-alkenyl)-2(5 H)-furanones. A possible mechanism is proposed.

Electrophilic interaction of 2,3-allenoates with PhSeCl. An unexpected highly stereoselective synthesis of 3-phenylseleno-4-oxo-2(E)-alkenoates.

We have previously reported an efficient synthesis of beta-phenylselenium-substituted butenolides via electrophilic cyclization of 2,3-allenoates with PhSeCl in aqueous MeCN. However, when 2,3-allenoates were treated with PhSeCl in MeCN, 3-phenylseleno-4-oxo-2(E)-alkenoates were formed unexpectedly. The addition of Li2CO3 improved the yield and the selectivity of the reaction. A possible mechanism involving a decomposition of selenate esters was proposed.

Ring-opening cyclization of alkylidenecyclopropyl ketones with amines. An efficient synthesis of 2,3,4-trisubstituted pyrroles.

An efficient synthesis of 2,3,4-trisubstituted pyrroles via intermolecular cyclization of alkylidenecyclopropyl ketones with amines was observed. The addition of anhydrous MgSO4 improved the yields of the products 3. A possible mechanism involving the distal cleavage of the C-C bond of cyclopropane ring was proposed.