Covalent Organic Framework-Based Theranostic Platforms for Restricting H1N1 Influenza Virus Infection.

Background: Influenza A (H1N1) virus is a highly contagious respiratory disease that causes severe illness and death. Vaccines and antiviral drugs are limited by viral variation and drug resistance, so developing efficient integrated theranostic options appears significant in anti-influenza virus infection. Methods: In this study, we designed and fabricated covalent organic framework (COF) based theranostic platforms (T705@DATA-COF-Pro), which was composed of an RNA polymerase inhibitor (favipiravir, T705), the carboxyl-enriched COF (DATA-COF) nano-carrier and Cy3-labeled single DNA (ssDNA) probe. Results: The multi-porosity COF core provided an excellent micro-environment and smooth delivery for T705. The ssDNA probe coating bound to the nucleic acids of H1N1 selectively, thus controlling drug release and allowing fluorescence imaging. The combination of COF and probe triggered the synergism, promoting drug further therapeutic outcomes. With the aid of T705@DATA-COF-Pro platforms, the H1N1-infected mouse models lightly achieved diagnosis and significantly prolonged survival. Conclusion: This research underscores the distinctive benefits and immense potential of COF materials in nano-preparations for virus infection, offering novel avenues for the detection and treatment of H1N1 virus infection.

Synthesis of covalent organic frameworks via Kabachnik-Fields reaction for water treatment.

Providing safe and clean domestic water for people is currently one of the greatest worldwide issues. In this context, heavy metal ions and pathogenic microbes are the two major factors in water pollution. The conventional water treatment methods, however, are generally high-energy and high-resource consumptive. Herein, we report, the first of its kind, the room-temperature synthesis of α-aminophosphonate-linked COFs via three-component one-pot in situ Kabachnik-Fields reaction (KF-3CR). Due to the coexistent bioactive α-aminophosphonate and photosensitive porphyrin, the obtained APCOF-1 exhibits highly efficient solar-powered bactericidal and heavy metal ion removal abilities, which allows it to be a promising COF-based multifunctional material for water treatment in an energy- and resource-saving way. Specifically, by incorporating APCOF-1 (up to 50 wt%) with eco-friendly and low-cost chitosan, an APCOF-1 @chitosan aerogel-based helical setup is fabricated via a facile templated freeze-drying approach and it can be a continuous flow-through water purifier model to achieve scaled-up water treatment through adsorptive removal of heavy metal ions and sunlight-driven sterilization. We believe that this research not only can significantly enrich the synthetic methodology of COFs, but also will hopefully bring COFs one step closer to the practical application.

Metalloporphyrin and Ionic Liquid-Functionalized Covalent Organic Frameworks for Catalytic CO2 Cycloaddition via Visible-Light-Induced Photothermal Conversion.

We report the construction of a porphyrin and imidazolium-ionic liquid (IL)-decorated and quinoline-linked covalent organic framework (COF, abbreviated as COF-P1-1) via a three-component one-pot Povarov reaction. After post-synthetic metallization of COF-P1-1 with Co(II) ions, the metallized COF-PI-2 is generated. COF-PI-2 is chemically stable and displays highly selective CO2 adsorption and good visible-light-induced photothermal conversion ability (ΔT = 26 °C). Furthermore, the coexistence of Co(II)-porphyrin and imidazolium-IL within COF-PI-2 has guaranteed its highly efficient activity for CO2 cycloaddition. Of note, the needed thermal energy for the reactions is derived from the photothermal conversion of the Co(II)-porphyrin COF upon visible-light irradiation. More importantly, the CO2 cycloaddition herein is a "window ledge" reaction, and it can proceed smoothly upon natural sunlight irradiation. In addition, a scaled-up CO2 cycloaddition can be readily achieved using a COF-PI-2@chitosan aerogel-based fixed-bed model reactor. Our research provides a new avenue for COF-based greenhouse gas disposal in an eco-friendly and energy- and source-saving way.

LncPVT1 promotes cartilage degradation in diabetic OA mice by downregulating miR-146a and activating TGF-ß/SMAD4 signaling.

INTRODUCTION: To investigate the role of LncRNA PVT1 (plasmacytoma variant translocation 1) in hyperglycemia-triggered cartilage damage using the diabetic osteoarthritis (OA) mice model. MATERIALS AND METHODS: Streptozotocin (STZ) was used to induce mouse diabetes. Knee OA model was induced through transection of anterior cruciate ligament (ACLT). Severity of arthritis was assessed histologically by Safranin O-Fast Green Staining using Mankin Scores. LncRNA PVT1 and miR-146a were detected by real-time polymerase chain reaction (PCR) in cartilage tissue. Moreover, the interaction among PVT1, miR-146a, and SMAD4 was examined by luciferase reporter assays. Mice were injected intra-articularly with ad-siRNA-PVT1 and ad-siRNA scramble control. Articular concentrations of TNF-α, IL-1, IL-6 and TGF-ß1 were determined using enzyme-linked immunosorbent assay. Levels of type II Collagen (COL2A1), TGF-ß1, p-SMAD2, SMAD2, p-SMAD3, SMAD3, SMAD4 and nuclear SMAD4 were detected by western blot analysis. RESULTS: PVT1 expression was significantly increased, whereas miR-146a was markedly decreased in diabetic OA mice than in non-diabetic OA and control. Increased PVT1 expression in diabetic OA mice was significantly associated with Mankin score and reduced miR-146a as well as Collagen alpha-1(II) (COL2A1) expressions. In vivo, intra-articular injection of ad-siRNA-PVT1 efficiently increased miR-146a and COL2A1 expressions, alleviated joint inflammation, decreased the expression of pro-inflammatory mediators, and suppressed TGF-ß/SMAD4 pathway in diabetic OA mice. CONCLUSIONS: Our results demonstrate LncRNA PVT1 is involved in cartilage degradation in diabetic OA and correlated with disease severity. Efficiency of ad-siRNA-PVT1 in controlling joint inflammation in diabetic OA mice is associated with the suppression of the expression of miR-146a, pro-inflammatory cytokines and activation of TGF-ß/SMAD4 pathway.

Sulfonic Acid and Ionic Liquid Functionalized Covalent Organic Framework for Efficient Catalysis of the Biginelli Reaction.

A quinoline-linked and ionic liquid-decorated covalent organic framework was prepared by incorporation of a multicomponent Povarov reaction and postsynthetic modification. The imidazolium and sulfonic acid-decorated COF-IM-SO3H can be a highly efficient Brønsted acid catalyst to promote the Biginelli reaction under solvent-free conditions in a heterogeneous way. In addition, a scaled-up Biginelli reaction has been readily realized over a COF-IM-SO3H@chitosan aerogel-based cup reactor.

Synergistic Antibacterial and Anti-Inflammatory Effects of a Drug-Loaded Self-Standing Porphyrin-COF Membrane for Efficient Skin Wound Healing.

Chronic wound infections resulting from severe bacterial invasion have become a major medical threat worldwide. Herein, we report a large-area, homogeneous, and self-standing porphyrin-covalent organic framework (COF)-based membrane with encapsulated ibuprofen (IBU) via an in situ interfacial polymerization and impregnation approach. The obtained IBU@DhaTph-membrane exhibits highly effective antibacterial and anti-inflammatory effects via synergistic light-induced singlet oxygen (1 O2 ) generation and controllable IBU release, which is well supported by in vitro experiments. In addition, the IBU@DhaTph-membrane-based biocompatible "band-aid" type dressing is fabricated, and its excellent anti-infection and tissue remodeling activities are fully evidenced by in vivo chronic wound-healing experiments. This study may inspire and promote the fabrication of many more new types of COF-based multifunctional biomaterials for various skin injuries in clinical medicine.

Decreased Synovial Fluid Biomarkers Levels Are Associated with Rehabilitation of Function and Pain in Rotator Cuff Tear Patients Following Electroacupuncture Therapy.

BACKGROUND The aim of this study was to assess inflammatory cytokines levels in synovial fluid (SF) before and after electroacupuncture (EA) treatment and to explore whether these biomarkers are associated with function of rotator cuff tear (RCT) patients. MATERIAL AND METHODS We recruited 54 patients with RCT and separated them into an EA group and a control group. The SF biomarker levels were detected at baseline and at 6-week and 6-month follow-up. The symptomatic severity was evaluated by visual analog scale (VAS), Constant-Murley score, and American Shoulder and Elbow Surgeons score (ASES). We also investigated the correlation between symptomatic severity and biomarker levels in SF of the shoulder joint. RESULTS The reductions in VAS and improved functional score (ASES and Constant-Murley score) were significantly different between the 2 groups, and SF biomarker concentrations were significantly lower in the EA group. IL-1ß levels were significantly negatively correlated with Constant-Murley score (r=-0.73, P=0.04) and ASES score (r=-0.59, P<0.001) and positively correlated with VAS scores (r=0.81, P=0.004). IL-6 levels were significantly negatively correlated with Constant-Murley score (r=-0.67, P=0.03) and positively correlated with VAS score (r=0.7, P=0.01). MMP-1 levels were significantly negatively correlated with ASES score (r=-0.57, P<0.001). CONCLUSIONS The biomarkers in SF were directly associated with shoulder pain and shoulder function in rotator cuff tear. EA, as a safe and effective conservative therapy, obviously decreased the level of inflammatory cytokines in RCT patients, accompanied by a reduction in shoulder pain and improved function.

[Effect of electroacupuncture on rehabilitation of knee joint movement after anterior cruciate ligament reconstruction].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on the rehabilitation of knee joint function after anterior cruciate ligament (ACL) reconstruction. METHODS: A total of 140 patients with ACL reconstruction were randomly divided into an observation group (58 cases recruited, 12 cases dropped out) and a control group (65 cases recruited, 5 cases dropped out). The patients in the control group were treated with routine rehabilitation treatment. The patients in the observation group, on the basis of the treatment in the control group, were treated with EA at Fengshi (GB 31), Futu (ST 32), Zusanli (ST 36), Shangjuxu (ST 37), Fenglong (ST 40), Xuanzhong (GB 39), Diji (SP 8) and Sanyinjiao (SP 6) on the affected side (2 Hz/100 Hz of dilatational wave, 2-5 mA). Each EA treatment lasted 20-30 min, twice a day for 7 days. The swelling degree (d), pain visual analogue scale (VAS), knee joint range of motion (ROM), scores of International Knee Documentation Committee (IKDC) subjective short form and scores of Lysholm were observed in the two groups 1 day, 1 month, 3 months, 6 months and 1 year after operation. RESULTS: One month and 3 months after operation, the swelling degree (d) and VAS scores in the observation group were lower than those in the control group (P<0.05); 6 months and 1 year after operation, there was no significant difference between the two groups on the swelling degree (d) and VAS scores (P>0.05). One month, 3 months, 6 months and 1 year after operation, the ROM of the knee joint in the observation group was higher than that in the control group (P<0.05), the IKDC score and Lysholm score were higher than those in the control group (P<0.05). Within one year, there were no relaxations, fractures and other related complications in the two groups. The pivot shift test, anterior drawer test and the Lachman test were all negative. CONCLUSION: EA combined with routine rehabilitation training could obviously reduce the pain of knee joint, improve the swelling degree, increase the ROM of knee joint, promote the functional recovery in patients with ACL reconstruction, which are superior to rehabilitation training alone.

Relationship between serum and synovial fluid CCL20 concentrations with disease severity in primary knee osteoarthritis.

OBJECTIVES: The current study was performed to examine serum and synovial fluid (SF) CCL20 levels and their correlations with disease severity in primary knee osteoarthritis patients. METHODS: A total of 99 patients diagnosed with primary knee OA were enrolled in the study, and 95 healthy individuals receiving regular medical examination were recruited as controls. Serum and SF CCL20 concentrations were determined using an enzyme-linked immunosorbent assay. The radiographic severity of OA was assessed by the Kellgren-Lawrence (K-L) classification system. The Lequesne algofunctional index and a visual analogue scale (VAS) were used to evaluate the clinical severity of knee OA in patients. RESULTS: The serum CCL20 levels were not significantly different between patients with knee OA and controls. Patients with a K-L grade of 4 had significantly higher SF CCL20 levels than those with K-L grades of 2 and 3. Knee OA patients with a K-L grade of 3 showed significantly higher levels of CCL20 in SF than those with a K-L grade of 2. In addition, SF CCL20 levels were significantly related to the Lequesne algofunctional index and VAS score. CONCLUSIONS: These findings suggest that local CCL20 levels may reflect the disease severity of knee OA.

Synovial fluid alpha-melanocyte-stimulating hormone may act as a protective biomarker for primary knee osteoarthritis.

OBJECTIVE: The current study was carried out to investigate the serum and synovial fluid (SF) alpha-melanocyte-stimulating hormone (α-MSH) levels in correlation with disease severity in primary knee osteoarthritis (OA). METHODS: This study comprised of 105 primary knee OA patients and 98 healthy controls. The radiographic severity was verified according to the Kellgren-Lawrence radiographic grading criteria. The symptomatic severity of knee OA was assessed by the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index. Serum α-MSH concentrations were measured by ELISA. The inflammation markers IL-6 and TNF-α, as well as cartilage damage markers MMP-3 (matrix metalloproteinase 3) and COMP (cartilage oligomeric matrix protein), were also measured. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value between α-MSH and other four markers with regard to the radiographic progression. RESULTS: SF α-MSH concentrations were negatively related to Kellgren-Lawrence grades and WOMAC index. SF α-MSH levels in knee OA patients were negatively associated with inflammation markers IL-6, TNF-α, and cartilage damage factors COMP and MMP-3. In addition, ROC analysis implied that attenuated α-MSH levels may serve as a favorable diagnostic marker for the radiographic progression. The difference of serum α-MSH concentration was not significant between knee OA patients and healthy controls. CONCLUSIONS: Reduced SF α-MSH expression may be a characteristic of OA patients. Attenuated α-MSH level in SF may serve as a potential biomarker for disease severity of knee OA, and further studies are needed to identify its potential application for monitoring the course of the disease and the efficacy of therapies in OA patients.

Pd NP-Loaded and Covalently Cross-Linked COF Membrane Microreactor for Aqueous CBs Dechlorination at Room Temperature.

We report an allyl-decorated and hydrazine-connected covalent organic framework (COF-AO, 1), which could support Pd nanoparticles (Pd NPs) to generate Pd@COF-AO, 2. The incorporation of 2 with thiol-functionalized polysiloxane (termed as PSI-SH) via thiol-ene click reaction provided the stand-alone and elastic membrane (3). The obtained COF-involved and Pd NP-loaded covalently linked membrane of 3 is robust, permanently porous, uniform, processable, and water permeable. Moreover, it can be used to construct highly efficient membrane-based microreactor for continuous-flow operation to catalyze chlorobenzenes (CBs) dechlorination in water at room temperature. The provided approach herein allows the processability and practical application of the powdered COF materials to be feasible.

Chemically Cross-Linked MOF Membrane Generated from Imidazolium-Based Ionic Liquid-Decorated UiO-66 Type NMOF and Its Application toward CO2 Separation and Conversion.

Carbon dioxide capture and transformation are of great importance to make cuts in greenhouse gas emissions. Nanometal-organic frameworks (NMOFs) could serve as ideal fillers for polymer membranes owing to their structural diversity and regulable microenvironment of the nanocage. Herein, a bifunctional, robust, and chemically cross-linked NMOF-based membrane was successfully constructed by the postsynthetic polymerization of imidazolium-based ionic liquid (IL)-decorated UiO-66 type nanoparticles (NPs) and the isocyanate-terminated polyurethane oligomer under mild conditions. The IL-modified MOF-polymer membranes exhibit a highly selective adsorption for CO2 over N2 and CH4. In addition, the obtained membrane can also be a highly active heterogeneous catalyst for CO2 transformation by cycloaddition with epoxide under an ambient pressure.

Smart pH-Responsive Polymer-Tethered and Pd NP-Loaded NMOF as the Pickering Interfacial Catalyst for One-Pot Cascade Biphasic Reaction.

A Pd nano particle (NP)-loaded and nano metal-organic framework (NMOF)-based Pickering emulsifier is reported. The poly[2-(diethylamino)ethyl methacrylate)] (PDEAEMA) chains were grafted onto UiO-66-type NPs via a postsynthetic approach to generate PDEAEMA-g-UiO-66 NMOF (termed as MOF-3). The Pd NPs-loaded Pd@MOF-3 was synthesized via solution impregnation. Stable toluene-in-water Pickering emulsion was prepared with emulsifier Pd@MOF-3. Notably, the obtained Pd@MOF-3 is pH-responsive, and it is able to trigger the emulsification (at neutral condition) and demulsification (at acidic condition) of toluene droplets. Furthermore, it can be a highly active interfacial catalyst to effectively promote one-pot Knoevenagel condensation-hydrogenation cascade reaction at ambient conditions. The pH-responsive property allowed it to be in situ separated and recycled by demulsifying via simply tuning the pH value at the end of the reaction. This smart Pickering emulsion catalytic system is robust, and it can be recycled at least five times without loss of its catalytic activity.

Bifunctional Imidazolium-Based Ionic Liquid Decorated UiO-67 Type MOF for Selective CO2 Adsorption and Catalytic Property for CO2 Cycloaddition with Epoxides.

A bifunctional robust and highly porous imidazolium-based ionic liquid decorated UiO-67 type MOF (UiO-67-IL, 1) was successfully constructed via solvothermal assembly of the imidazolium-based ligand and Zr(IV) ions. It exhibits a highly selective adsorption for CO2 over CH4 and N2. Furthermore, 1 herein can be used as a highly active heterogeneous catalyst for CO2 cycloaddition with epoxides under atmospheric pressure with or without cocatalyst TBAB (n-Bu4NBr).

A MOF-membrane based on the covalent bonding driven assembly of a NMOF with an organic oligomer and its application in membrane reactors.

A UiO-66-MOF-based membrane UiO-66-TEM (1) was prepared by the assembly of methacrylamide-decorated UiO-66-NH-Met with a thiol side chain-attached polysiloxane (PSI-SH) via a photoinduced thiol-ene click reaction. The obtained membrane 1 can be a platform to support Au nanoparticles (Au NPs) to generate an Au-MOF-polymer composite membrane Au@UiO-66-TEM (2). 1 and 2 can be used to build highly efficient continuous flow-through membrane reactors for Knoevenagel condensation of 4-nitrobenzaldehyde with malononitrile and 4-nitrophenol (4-NP) reduction at ambient temperature, respectively.

Possible Involvement of Serum and Synovial Fluid Resistin in Knee Osteoarthritis: Cartilage Damage, Clinical, and Radiological Links.

BACKGROUND: Resistin is an adipocytokine associated with inflammation and insulin resistance. Recent studies have shown that resistin plays an important role in the pathogenesis and progression in osteoarthritis (OA) patients. The current study was aimed at investigating the relationship between resistin in serum and synovial fluid (SF) and disease severity in patients with knee osteoarthritis. METHOD: Seventy-four patients diagnosed with knee OA and 79 healthy controls receiving regular body check in our hospital were recruited in the study. The Noyes score method was used to assess articular cartilage damage arthroscopically. The symptomatic severity was evaluated according to the Western Ontario McMaster University Osteoarthritis (WOMAC) scores. The radiographic disease severity of OA was assessed by the Kellgren-Lawrence (K-L) grading system. The resistin levels in serum and SF were determined by enzyme-linked immunosorbent assay. Cartilage degradation marker CTX-II in SF was also examined. RESULTS: SF but not serum resistin levels are positively associated with Noyes scores, K-L grading scores WOMAC pain scores, physical functional scores and WOMAC total scores. In addition, SF resistin correlated positively with CTX-II. CONCLUSION: Resistin in SF might serve as a potential biomarker for reflecting the disease severity and cartilage degenerative extent of knee OA.

Increased Synovial Fluid YKL-40 Levels are Linked with Symptomatic Severity in Knee Osteoarthritis Patients.

BACKGROUND: Elevated serum and synovial fluid (SF) YKL-40 levels have been detected in knee osteoarthritis (OA) patients. The current study was focused on the correlation between YKL-40 levels in serum or SF and symptomatic severity in patients with knee osteoarthritis. METHODS: 144 patients with knee OA and 151 healthy individuals were recruited into this study. Symptomatic severity was determined using Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores from OA patients. Serum and SF levels of YKL-40 were explored by enzyme-linked immunosorbent assay. RESULTS: We found that YKL-40 levels in SF but not serum were independently and positively related to WOMAC pain (r = 0.531, p = 0.001), physical disability (r = 0.380, p = 0.025), and total scores (r = 0.407, p = 0.01) in knee OA patients. CONCLUSIONS: YKL-40 in SF could represent a potential biomarker for assessing the symptomatic severity of OA.

Treatment of malignant liver tumors by radiofrequency ablation combined with low-frequency ultrasound radiation with microbubbles.

OBJECTIVE: To explore the therapeutic efficacy and safety of malignant liver tumor treatment by radiofrequency ablation (RA) combined with low frequency ultrasound radiation with microbubbles (LFURM). METHODS: Retrospective analysis of 25 patients with malignant hepatic tumors treated by RA/LFURM in the Department of Hepatobiliary Surgery of Kunming General Hospital affiliated to Chengdu Military District, PLA from January 2010 to June 2011. Ultrasound guided RA was performed, which was followed one week later by LFURM. Basal contrast ultrasound, liver function tests, and serum alpha fetoprotein (AFP) were obtained, and repeated 3 and 6 months after treatment. T-test and chi-square were used to compare parametric and non-parametric variables respectively. RESULTS: In 17 cases, gross tumor volume was significantly reduced 6 months after treatment while mean tumor showed a reduction of 50% compared to pre-treatment values. In 7 cases gross tumor volumes reduction was partial, but surrounding tumor tissue showed blood flow signals. One patient had no reduction in gross tumor volume. Levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), alpha fetoprotein (AFP) decreased significantly 6 months after treatment (all p<0.05). No tumor recurrence was seen during the 6 month follow-up. Quality of life scores (QOL) were good in 21 patients (84%), improved in 2 patients (8%), unchanged in 1 patient (4%) and got worst in 1 patient (4%). Karnofsky scores (KPS) improved in 19 patients (76%), remained unchanged in 5 patients (2%) and got worst in 1 patient (4%). Both QOL and KPS changes were statistically significant (P<0.05). CONCLUSION: RA/LFURM treatment of liver tumors is efficient and safe, and can reduce the gross tumor volumes and protect liver function.

[Acupuncture treatment of regulating spirit, activating blood and relieving pain for thalamic pain].

OBJECTIVE: To compare the clinical effect of acupuncture treatment and western medicine Carbamazepine for thalamic pain. METHODS: Crossover trial design was used, 11 cases diagnosed as thalamic pain were randomly divided into two groups according to the mini-unbalance-index method, group I (with 6 cases received acupuncture first and then western medicine) and group II (with 5 cases received western medicine first and then acupuncture). When the effects were evaluated, the two groups were named as acupuncture group and western medicine group, 11 cases in each group. The method of clearing away the heart fire, regulating the spirit, activating blood and relieving pain was adopted in acupuncture treatment, Ximen (PC 4), Yinxi (HT 6), Xuehai (SP 10) and Zhaohai (KI 6) were selected; the western medicine group was treated with oral administration of Carbamazepine, and one course as well as the eluting period were both 10 days. The effects were evaluated with visual analogue scale (VAS) and evaluation scale of Anderson Cancer Center pain in US (MD Pain Evaluation value) respectively. RESULTS: The VAS and MD value in two groups were obviously decreased after treatment (both P < 0.05), while there was no significant difference between two groups; the markedly effective rate of pain relieving in acupuncture group was 63.6% (7/11), which was higher than that of 36.4% (4/11) in western medicine group, but there was no significant difference between two groups. CONCLUSION: Acupuncture treatment of regulating spirit, activating blood and relieving pain has a better therapeutic effect for thalamic pain, and can reach to the same therapeutic effect with western medicine Carbamazepine.