Inflammation-Responsive Mesoporous Silica Nanoparticles with Synergistic Anti-inflammatory and Joint Protection Effects for Rheumatoid Arthritis Treatment.

PURPOSE: Joint destruction is a major burden and an unsolved problem in rheumatoid arthritis (RA) patients. We designed an intra-articular mesoporous silica nanosystem (MSN-TP@PDA-GlcN) with anti-inflammatory and joint protection effects. The nanosystem was synthesized by encapsulating triptolide (TP) in mesoporous silica nanoparticles and coating it with pH-sensitive polydopamine (PDA) and glucosamine (GlcN) grafting on the PDA. The nano-drug delivery system with anti-inflammatory and joint protection effects should have good potency against RA. METHODS: A template method was used to synthesize mesoporous silica (MSN). MSN-TP@PDA-GlcN was synthesized via MSN loading with TP, coating with PDA and grafting of GlcN on PDA. The drug release behavior was tested. A cellular inflammatory model and a rat RA model were used to evaluate the effects on RA. In vivo imaging and microdialysis (MD) system were used to analyze the sustained release and pharmacokinetics in RA rats. RESULTS: TMSN-TP@PDA-GlcN was stable, had good biocompatibility, and exhibited sustained release of drugs in acidic environments. It had excellent anti-inflammatory effects in vitro and in vivo. It also effectively repaired joint destruction in vivo without causing any tissue toxicity. In vivo imaging and pharmacokinetics experiments showed that the nanosystem prolonged the residence time, lowered the Cmax value and enhanced the relative bioavailability of TP. CONCLUSIONS: These results demonstrated that MSN-TP@PDA-GlcN sustained the release of drugs in inflammatory joints and produced effective anti-inflammatory and joint protection effects on RA. This study provides a new strategy for the treatment of RA.

Endowing Polyetheretherketone Implants with Osseointegration Properties: In Situ Construction of Patterned Nanorod Arrays.

Polyetheretherketone (PEEK) is widely used in orthopedic and craniomaxillofacial surgeries as it exhibits excellent biocompatibility, mechanical property, and chemical stability. However, its clinical application is limited by the biological inertness of PEEK. Numerous efforts have been made to improve the bioactivity of this polymer over the years. However, modification methods that can not only promote osteogenesis but also maintain excellent properties are still limited. Hence, a facile hot die formation technique is developed for establishing patterned nanorod arrays on the PEEK surface in situ. This method can maintain the excellent properties of PEEK and can be used in implantation as it can facilitate osteogenic activity in the absence of any organic/inorganic differentiation-inducing factors. PEEK with 200-nm patterned nanorod arrays on the surface exhibits excellent osteogenic properties. This result is obtained by assessing the osteogenic differentiation properties of rat adipose-derived stem cells at the gene and protein levels in vitro. In vivo experimental results reveal that the surface-modified cylindrical PEEK 200 implants present with excellent osseointegration properties. Moreover, they can tightly bind with the surrounding bone tissue. A practical method for manufacturing single-component PEEK implants with excellent osseointegration properties is reported, and the materials can be possibly used as orthopedic implants.

Fiber Lateral Pressure Sensor Based on Vernier- Effect Improved Fabry-Perot Interferometer.

A fiber optic pressure sensor that can survive 2200 psi and 140 °C was developed. The sensor's pressure sensitivity was measured to be 14 times higher than bare FBG when tested inside stacks of ultra-high-molecular-weight polyethylene (UHMWPE) composite fabric. The sensitivity can be further improved 6-fold through the Vernier effect. Its tiny sensing length (hundreds of microns) and uniform outer diameter (125 µm) make it a suitable candidate for real-time point pressure monitoring under harsh environments with limited space, such as in composite-forming procedures.

Diagnostic value of loop-mediated isothermal amplification assay for hand, foot, and mouth disease.

BACKGROUND: Nowadays, hand, foot, and mouth disease (HFMD) has a significant negative impact on children's health, especially in the Asia-Pacific region. Loop-mediated isothermal amplification assay (LAMP) is a highly efficient and convenient novel tool. However, its diagnostic accuracy for HFMD is still not clear. Therefore, we conducted a meta-analysis in order to evaluate the potential of LAMP assay for the diagnosis of HFMD, in which the reference standard was polymerase chain reaction (PCR). METHODS: A protocol was predetermined (CRD42020212882) in PROSPERO. We retrieved seven databases including PubMed for relevant studies published before October 2020. Articles were included if they compared the diagnostic efficiency of LAMP with PCR for HFMD through detecting clinical samples which was more than 15. Statistical analysis was performed by STATA 15.1 software. Risk of bias and applicability were assessed using Quality Assessment of Diagnostic Accuracy Studies. No funding was used for the study. RESULTS: A total of 18 retrospective studies including 2495 samples from China were finally included. Reference standards of them included RT-PCR and non-RT-PCR. The merged sensitivity and specificity with 95% confidence interval (95% CI) were 1.00 (0.97-1.00) and 0.97 (0.88-0.99), respectively. The pooled PLR, NLR, and DOR with 95% CI were 11.17 (5.91-21.11), 0.05 (0.03-0.09), and 538.12 (183.17-1580.83), respectively. The AUC of SROC was 1.00 (95% CI: 0.99-1.00). CONCLUSION: In conclusion, our research revealed high sensitivity and specificity of LAMP in diagnosing HFMD. However, more high-quality research is required to prove this conclusion.

A stretchable conductive Polypyrrole Polydimethylsiloxane device fabricated by simple soft lithography and oxygen plasma treatment.

This paper reports a simple method used to fabricate a stretchable conductive polypyrrole (PPy) rough pore-shape polydimethylsiloxane (p-PDMS) device. An abrasive paper is first used to imprint rough micro-structures on the SU-8 micromold. The p-PDMS microchannel is then fabricated using a standard soft-lithography process. An oxygen plasma treatment is then applied to form an irreversible sealing between the microchannel and a blank cover PDMS. The conductive layer is formed by injecting the PPy mixture into the microchannel which polymerizes in the rough pore-shape micro-structures; The PPy/p-PDMS hybrid device shows good electrical property and stretchability. The electrical properties of different geometrical designs of the PPy/p-PDMS microchannel under stretching were investigated, including straight, curved, and serpentine. Mouse embryonic fibroblasts (NIH/3 T3) were also cultured inside the PPy/p-PDMS device to demonstrate good biocompatibility and feasibility using the conductive and stretchable microchannel in cell culture microfluidics applications. Finally, cyclic stretching and bending tests were performed to evaluate the reliability of PPy/p-PDMS microchannel.

A prospective study on the safety and effectiveness of using lauromacrogol for ablation of pancreatic cystic neoplasms with the aid of EUS.

BACKGROUND AND AIMS: With the development of imaging techniques, the detection rate of pancreatic cystic neoplasms (PCNs) has increased. The surgical morbidity and mortality rates of PCNs are quite high. This study is intended to evaluate the safety and effectiveness of a minimally invasive treatment, EUS-guided PCN ablation with lauromacrogol. METHODS: From April 2015 to May 2016, 120 patients with PCNs were enrolled to undergo EUS. We prospectively studied 29 of the 120 patients who underwent EUS-guided ablation with lauromacrogol. The follow-up contrast-enhanced CT or magnetic resonance image was conducted at 3 months and then 6 months after ablation. We determined the effectiveness of ablation by the changes in the volume of the cysts. RESULTS: Twenty-nine patients were enrolled in the study, and 7 of them underwent a second ablation; therefore, there were 36 treatments. The mean tumor diameter was 28.6 ± 14.5 mm preoperation, whereas the diameter postoperation was 13.4 ± 10.5 mm. Mild pancreatitis occurred in 2 patients and moderate fever in 1; they occurred in the cysts located in the head/uncinate. Among the 29 treatments with complete follow-up of 9 months (range, 3-15), 11 had complete response and 9 had partial response. The resolution rate was 37.9% (11/29) with 36.4% (8/22) in the cysts of the head/uncinate and 42.9% (3/7) in the body/tail (P > .05). CONCLUSIONS: EUS-guided PCN ablation with lauromacrogol is safe and efficient. Adverse event rates seem to be higher in the head/uncinate than in the body/tail, but their resolution rates are similar. Further studies involving larger populations and longer follow-ups are warranted.

High selectivity molecularly imprinted polymer based on short amylose as bio-based functional monomers for selective extraction of λ-cyhalothrin.

Nowadays, the development of sustainable molecularly imprinted polymers (MIPs) with high selectivity is still challenging due to the limitations of bio-based functional monomers. In this study, the highly selective and porous MIPs (LC-TMIPs) were designed and prepared on short amylose (SAM) as bio-based functional monomers, λ-cyhalothrin (LC) as a template molecule, and tetrafluoroterephthalonitrile as a rigid crosslinking agent. Static, dynamic, and selective adsorption experiments were conducted to investigate the adsorption performance. The results indicated that, compared to MIPs prepared using epichlorohydrin as flexible crosslinking agents, LC-TMIPs exhibited higher imprinting factor (3.93), selectivity (5.78), and adsorption capacity (35.79 mg g-1), as well as faster adsorption/desorption kinetics. The LC-TMIPs were used as sorbents for the selective determination of LC in both apple and cucumber samples by high-performance liquid chromatography. Under the optimal extraction conditions, the recoveries of the method reached 92.1-106.1 %, with a linear range of 1.5-30 ng g-1 and a detection limit of 0.5 ng g-1. The proposed preparation method of LC-TMIPs is expected to open a new way to prepare highly selective and sustainable MIPs for hydrophobic compounds.

Fractionated lignin as a polyol in polyurethane fabrication.

The main purpose of this paper was to systematically evaluate the effect of lignin, which was fractioned by green solvents into different molecular weights and used as polyol in the production of polyurethane foams (PUF). The results indicated that the foams prepared with the lower molecular weight lignin had uniform and complete pore structure and improved the mechanical strength. However, the higher molecular weight fraction lignin improved the density and thermal stability of the foam more significantly at the expense of inferior mechanical strength and pore structure deficiency. When the substitution degree of lignin in the PUF was 2 %-30 %, 99.13 % of the lowest molecular weight lignin was participated in the reaction to produce PUF, which improved the elongation at break (Eb) and tensile strength (Ts) of PUF to 834 % and 0.90 MPa, respectively. Also, thermal stability and the amount of unreacted lignin in PUF were increased at a higher substitution degree of lignin in PUF.

Highly Sensitive Flexible Capacitive Pressure Sensor Based on a Multicross-Linked Dual-Network Ionic Hydrogel for Blood Pressure Monitoring Applications.

Flexible capacitive pressure sensors based on ionic hydrogels (IHs) have garnered significant attention in the field of wearable technology. However, the vulnerability of traditional single-network hydrogels to mechanical damage and the complexity associated with preparing double-network hydrogels present challenges in developing a highly sensitive, easily prepared, and durable IH-based flexible capacitive pressure sensor. This study introduces a novel multicross-linked dual-network IH achieved through the physical and chemical cross-linking of polymers polyvinyl alcohol (PVA) and chitosan (CS), ionic solution H3PO4, and cross-linking agent gum arabic. Flexible capacitive pressure sensors, characterized by high sensitivity and a broad pressure range, are fabricated by employing mesh as templates to design cut-corner cube microstructures with high uniformity and controllability on the IHs. The sensor exhibits high sensitivity across a wide pressure range (0-290 kPa) and with excellent features such as high resolution (∼1.3 Pa), fast response-recovery time (∼11 ms), and repeatable compression stability at 25 kPa (>2000 cycles). The IHs as a dielectric layer demonstrate long-term water retention properties, enabling exposure to air for up to 100 days. Additionally, the developed sensor shows the ability to accurately measure the pulse wave within the small pressure range. By combining the pulse wave acquired by the sensor with a trained neural network model, we achieve successful blood pressure (BP) prediction, meeting the standards set by the Association for the Advancement of Medical Instrumentation and the British Hypertension Society. Ultimately, the sensor proposed in this study holds promising prospects for broad applications in high-precision wearable medical electronic devices.

Evaluating the hypolipidemic effect of garlic essential oil encapsulated in a novel double-layer delivery system.

The limited application of garlic essential oil (GEO) is attributed to its pungent taste, poor water solubility and low bioavailability. Liposomes are nontoxic, biodegradable and biocompatible, and ß-cyclodextrin can inhibit undesirable odors and improve the stability and bioavailability. Thus a promising dual-layer GEO ß-cyclodextrin inclusion compound liposome (GEO-DCL) delivery system with both advantages was designed and prepared in this study. Experimental results indicated that the encapsulation efficiency of GEO-DCLs was 5% higher than that of GEO liposomes (GEO-CLs), reaching more than 88%. In vitro release experiment showed that the release rate of GEO in GEO-DCLs was 40% lower than that of GEO-CLs after incubation in gastric juice for 6-h, indicating that the stability of GEO-DCLs was better than GEO-CLs. Evaluation of the effects of GEO-DCLs on lowering blood lipid levels in hypercholesterolemia mice. GEO-DCLs could reduce the weight and fat deposition in hypercholesterolemia mice. Inhibiting the increase of TC, LDL-C, and decrease of HDL-C in mice. The degree of liver injury was decreased, the number of round lipid droplets in liver cytoplasm was reduced, and the growth of fat cells was inhibited. The lipid-lowering effects of GEO-DCLs were dose-dependent. GEO-DCL can improve the bioavailability of GEO and improve dyslipidemia. Based on GEO's efficacy in lowering blood lipids, this study developed a kind of GEO-DCL compound pomegranate juice beverage with good taste, miscibility and double effect of reducing blood lipids. This study lays a foundation for the application of GEO in the field of functional food.

Coffee consumption and periodontitis: a Mendelian Randomization study.

BACKGROUND: Coffee is one of the most consumed beverages in the world, coffee consumption has been growing in the United States over the past 20 years. Periodontitis is defined by the pathologic loss of the periodontal ligament and destruction of the connective tissue attachment and alveolar bone loss and is related to different systemic diseases and conditions. However, the causality has remained unclarified, thus we regarded discovering the causal relationship between coffee consumption and the liability to periodontitis as the objective of the study. METHODS: Coffee consumption was subdivided into binary coffee consumption and continuous coffee consumption to refine the study design. Genetic instruments were stretched from the MRC-IEU's (MRC Integrative Epidemiology Unit) output from the GWAS pipeline using phesant-derived variables based on the UK Biobank, the Gene-Lifestyle Interactions in Dental Endpoints (GLIDE) project, and the joint meta-analysis of a recent GWAS. The IVW (Inverse Variance Weighted) was regarded as the primary method to estimate the causality, a scatter plot revealed the intuitive result, and tests for stability were also carried out. RESULTS: An effect of continuous coffee consumption on the risk of periodontitis was found, with per SD of coffee consumed increases, the risk of periodontitis rises by 1.04% (Odds Ratio of IVW is 1.0104), while the effect of binary coffee consumption on periodontitis did not meet the requirement of indicating a strong causal association, neither were the reverse causality analyses. CONCLUSIONS: The study indicated the causality of continuous coffee consumption to the risk of periodontitis with a relatively small scale of effect estimate and no strong evidence for an effect of binary coffee-consuming behavior on periodontitis. There was also no intensive evidence suggesting reverse causality.

Soft, bioresorbable coolers for reversible conduction block of peripheral nerves.

Implantable devices capable of targeted and reversible blocking of peripheral nerve activity may provide alternatives to opioids for treating pain. Local cooling represents an attractive means for on-demand elimination of pain signals, but traditional technologies are limited by rigid, bulky form factors; imprecise cooling; and requirements for extraction surgeries. Here, we introduce soft, bioresorbable, microfluidic devices that enable delivery of focused, minimally invasive cooling power at arbitrary depths in living tissues with real-time temperature feedback control. Construction with water-soluble, biocompatible materials leads to dissolution and bioresorption as a mechanism to eliminate unnecessary device load and risk to the patient without additional surgeries. Multiweek in vivo trials demonstrate the ability to rapidly and precisely cool peripheral nerves to provide local, on-demand analgesia in rat models for neuropathic pain.

A Poly-Chitosan and Cis-Platinum Conjugated Composite Nanoparticle System for Liver Cancer Therapy.

The aim of this study was to test an effective nano-pole capsule loaded cis-platinum (CP) transplantation device for liver cancer (LC) therapy. A novel nano-pole capsule was designed as a new vector for storing CP. HepG2 cells and a B6/J mouse model were used to test the efficiency of polyethyleneimine-cis-platinum (PEI-CP) and poly-chitosan-cis-platinum (PC-CP). Infiltration efficiency and transplantation efficiency tests were performed to study the performance of the delivery system, and fibroblast reactions and macrophage numbers were observed, to test for immune rejection and foreign body reactions. The apoptosis rate and tumor diameter of hepatocellular carcinoma cells were used to evaluate the effect of the tumor therapy. We also studied the functional mechanism of different CP delivery systems. The infiltration and transplantation efficiencies of PC-CP were higher than that of PEI-CP; Less foreign body reaction appeared in PC system, with less fibroblast reaction and lower macrophage reaction. The clinical efficacy of PC-CP in terms of tumor apoptosis and diameter reduction was superior to that of PEI-CP. We demonstrated that PC-CP had a more significant alteration effect on mTOR, P-Ak, LC3 and P53. The PC system can better deliver and release drugs than PEI-CP, and may be a better choice for LC therapy in the future.

[Effects on lymphangiogenesis and angiogenesis of lung cancer with antisense oligonucleotides of vascular endothelial growth factor C].

OBJECTIVE: To investigate the effects on lymphangiogenesis and angiogenesis of orthotopic implantation of lung cancer in nude mice with antisense oligonucleotides of VEGF-C. METHODS: The model in nude mice was established with orthotopic implantation for the human lung cancer cell line A549. Thirty nude mice were randomized into three groups: PBS control group, sense oligonucleotides control group and antisense oligonucleotides group (AODN group). After treatments were completed, the expression of VEGF-C and lymphatic microvessel density (LMVD) and microvessel density (MVD) of lung cancer were detected by RT-PCR,Western Blot and immunohistochemistry. RESULTS: The expression of VEGF-C in AODN group was inhibit significantly (P < 0.05). The LMVD in AODN group was decreased significantly (P < 0.1). Though the MVD in AODN group was also decreased, but there were no significant differences compared with control groups (P > 0.05). CONCLUSIONS: The antisense oligonucleotides of VEGF-C can inhibit the expression of VEGF-C in nude mice of orthotopic implantation of lung cancer. It could inhibit the lymphangiogenesis.

Bioinspired Ferroelectric Polymer Arrays as Photodetectors with Signal Transmissible to Neuron Cells.

A bioinspired photodetector with signal transmissible to neuron cells is fabricated. Photoisomerization of the dye molecules embedded in the ferroelectric polymer membrane achieves electric polarization change under visible light. The photodetector realizes high sensitivity, color recognition, transient response, and 3D visual detection with resolution of 25 000 PPI, and, impressively, directly transduces the signal to neuron cells.

NELL1 promotes bone regeneration in polyethylene particle-induced osteolysis.

We investigated the therapeutic effects of a craniosynostosis-associated molecule, NEL-like molecule-1 (NELL1; NEL [a protein strongly expressed in neural tissue encoding the epidermal growth factor-like domain]), on osteolysis induced by polyethylene (PE)-particle debris. We used a murine calvarial osteolysis model with in vivo adenovirus (Ad)-mediated gene transfer. In total, 76 female Balb/c mice were randomly assigned to four groups for treatment 1 day postoperation: SHAM (injected with 0.1 mL saline without implantation of particles); PE control (injected with 0.1 mL saline after implantation of particles); PE+(Ad-GFP-NELL1) (injected with 0.1 mL Ad-GFP-NELL1 in saline after implantation of particles); and PE+(Ad-GFP) group (injected with 0.1 mL Ad-GFP in saline after implantation of particles). Green fluorescent protein (GFP) and NELL1 delivery in vivo after the injection were validated by optical imaging at 10 day postop, and then, all mice were sacrificed for analysis by three-dimensional (3D) microcomputed tomography (micro-CT), real-time polymerase chain reaction (PCR), histology, and biomechanical testing. Exogenous NELL1 and GFP were expressed in the osteolysis area for at least 9 days after the Ad-GFP-NELL1 injection. Serial 3D micro-CT images and testing of bone volume, bone mineral density, trabecular thickness, bone surface density, and connectivity density revealed that the new bone promoted with the Ad-GFP-NELL1 injection could almost compensate the PE-induced osteolysis and regenerate significantly better than with the Ad-GFP treatment. The expression of osteopontin (OPN) was significantly higher with Ad-GFP-NELL1 transduction among all the samples. Real-time PCR examination confirmed the augmented expression of OPN, Runx-2, and receptor activator of nuclear factor-kappa B ligand (RANKL). The elastic modulus was significantly greater with Ad-GFP-NELL1 than with the PE and/or Ad-GFP group (p<0.01). We found no transgene-associated toxic effects. Ad-GFP-NELL1 gene transfer effectively reversed the calvarial osteolysis and could be considered a new treatment for osteolysis through promoting bone regeneration.