Hydrogel-Coated SERS Microneedles for Drug Monitoring in Dermal Interstitial Fluid.

In vivo drug monitoring is crucial for evaluating the effectiveness and safety of drug treatment. Blood sampling and analysis is the current gold standard but needs professional skills and cannot meet the requirements of point-of-care testing. Dermal interstitial fluid (ISF) showed great potential to replace blood for in vivo drug monitoring; however, the detection was challenging, and the drug distribution behavior in ISF was still unclear until now. In this study, we proposed surface-enhanced Raman spectroscopy (SERS) microneedles (MNs) for the painless and real-time analysis of drugs in ISF after intravenous injection. Using methylene blue (MB) and mitoxantrone (MTO) as model drugs, the innovative core-satellite structured Au@Ag SERS substrate, hydrogel coating over the MNs, rendered sensitive and quantitative drug detection in ISF of mice within 10 min. Based on this technique, the pharmacokinetics of the two drugs in ISF was investigated and compared with those in blood, where the drugs were analyzed via liquid chromatography-mass spectrometry. It was found that the MB concentration in ISF and blood was comparable, whereas the concentration of MTO in ISF was 2-3 orders of magnitude lower than in blood. This work proposed an efficient tool for ISF drug monitoring. More importantly, it experimentally proved that the penetration ratio of blood to ISF was drug-dependent, providing insightful information into the potential of ISF as a blood alternative for in vivo drug detection.

Inflammatory bowel disease alters in vivo distribution of orally administrated nanoparticles: Revealing via SERS tag labeling technique.

Nanoparticles (NPs) could be uptake orally and exposed to digestive tract through various sources such as particulate pollutant, nanomedicine and food additive. Inflammatory bowel disease (IBD), as a global disease, induced disruption of the intestinal mucosal barrier and thus altered in vivo distribution of NPs as a possible consequence. However, related information was relatively scarce. Herein, in vivo distribution of typical silica (SiO2) and titania (TiO2) NPs was investigated in healthy and IBD models at cell and animal levels via a surface-enhanced Raman scattering (SERS) tag labeling technique. The labeled NPs were composed of gold SERS tag core and SiO2 (or TiO2) shell, demonstrating sensitive and characteristic SERS signals ideal to trace the NPs in vivo. Cell SERS mapping revealed that protein corona from IBD intestinal fluid decreased uptake of NPs by lipopolysaccharide-induced RAW264.7 cells compared with normal intestinal fluid protein corona. SERS signal detection combined with inductively coupled plasma mass spectrometry (ICP-MS) analysis of mouse tissues (heart, liver, spleen, lung and kidney) indicated that both NPs tended to accumulate in lung specifically after oral administration for IBD mouse (6 out of 20 mice for SiO2 and 4 out of 16 mice for TiO2 were detected in lung). Comparatively, no NP signals were detected in all tissues from healthy mice. These findings suggested that there might be a greater risk associated with the oral uptake of NPs in IBD patients due to altered in vivo distribution of NPs.

Molecular Imprinting-Based SERS Detection Strategy for the Large-Size Protein Quantitation and Curbing Non-Specific Recognition.

Molecular imprinting-based surface-enhanced Raman scattering (MI-SERS) sensors have shown remarkable potential from an academic standpoint. However, their practical applications, especially in the detection of large-size protein (≥10 nm), face challenges due to the lack of versatile sensing strategies and nonspecific fouling of matrix species. Herein, we propose a Raman reporter inspector mechanism (RRIM) implemented on a protein-imprinted polydopamine (PDA) layer coated on the SERS active substrate. In the RRIM, after large-size protein recognition, the permeability of the PDA imprinted cavities undergoes changes that are scrutinized by Raman reporter molecules. Target proteins can specifically bind and fully occupy the imprinted cavities, whereas matrix species cannot. Then, Raman reporter molecules with suitable size are introduced to serve as both inspectors of the recognition status and inducers of the SERS signal, which can only penetrate through the vacant and nonspecifically filled cavities. Consequently, changes in the SERS signal exclusively originate from the specific binding of target proteins, while the nonspecific recognition of matrix species is curbed. The RRIM enables reproducible quantitation of the large-size cyanobacteria-specific protein model (≥10 nm), phycocyanin, at the level down to 2.6 × 10-3 µg L-1. Finally, the practical applicability of the RRIM is confirmed by accurately analyzing crude urban waterway samples over 21 min without any pretreatment.

Comparison Between Intraoperative Target Area Cement-Enhanced Percutaneous Vertebroplasty and Conventional Percutaneous Vertebroplasty for Osteoporotic Thoracolumbar Non-Total Vertebral Fractures.

AIM: To compare the efficacy and feasibility of target area cement-enhanced percutaneous vertebroplasty (PVP) and conventional PVP in osteoporotic thoracolumbar non-total vertebral fractures. MATERIAL AND METHODS: Retrospective analysis of one hundred and two patients treated in our hospital from March 2020 to May 2021 and divided into groups A (targeted) and B (conventional PVP). The Visual Analogue Scale (VAS), Oswestry Disability Index (ODI), anterior vertebral height ratio, intraoperative bleeding, operative time, bone cement volume, complications, and refracture of the injured vertebra were evaluated in both groups. RESULTS: The 2 days and 1-year post-operative VAS and ODI scores improved significantly in both groups (p < 0.05). The 2 days post-operative VAS and ODI scores were better in group A (p < 0.05), and there was no significant difference in the scores between the groups at the last follow-up (p > 0.05). The anterior vertebral height ratios were significantly higher in both groups 2 days postoperatively (p < 0.05); however, there was no significant difference in the 2 days and 1-year post-operative ratios in group A (p > 0.05). The anterior vertebral height ratio reduced in group B after 1 year compared to the 2 days post-operative value (p < 0.05). There was no statistical difference in intraoperative bleeding and the operative time between the groups (p > 0.05), and the bone cement volume was lesser in group A (p < 0.05). Six patients in group A and four patients in group B demonstrated cement leakage, the difference was not statistically significant (p > 0.05). Three patients in group A and 11 patients in group B demonstrated refracture, the difference was statistically significant (p < 0.05). CONCLUSION: Target area cement-enhanced PVP can effectively relieve short-term pain and functional disability and reduce the long-term possibility of secondary collapse. Therefore, it is a technically feasible and efficacious method for the treatment of osteoporotic thoracolumbar non-total vertebral fractures.

Biomechanical study of different bone cement distribution on osteoporotic vertebral compression Fracture-A finite element analysis.

Purpose: This study aimed to compare the biomechanical effects of different bone cement distribution methods on osteoporotic vertebral compression fractures (OVCF). Patients and methods: Raw CT data from a healthy male volunteer was used to create a finite element model of the T12-L2 vertebra using finite element software. A compression fracture was simulated in the L1 vertebra, and two forms of bone cement dispersion (integration group, IG, and separation group, SG) were also simulated. Six types of loading (flexion, extension, left/right bending, and left/right rotation) were applied to the models, and the stress distribution in the vertebra and intervertebral discs was observed. Additionally, the maximum displacement of the L1 vertebra was evaluated. Results: Bone cement injection significantly reduced stress following L1 vertebral fractures. In the L1 vertebral body, the maximum stress of SG was lower than that of IG during flexion, left/right bending, and left/right rotation. In the T12 vertebral body, compared with IG, the maximum stress of SG decreased during flexion and right rotation. In the L2 vertebral body, the maximum stress of SG was the lowest under all loading conditions. In the T12-L1 intervertebral disc, compared with IG, the maximum stress of SG decreased during flexion, extension, and left/right bending and was basically the same during left/right rotation. However, in the L1-L2 intervertebral discs, the maximum stress of SG increased during left/right rotation compared with that of IG. Furthermore, the maximum displacement of SG was smaller than that of IG in the L1 vertebral bodies under all loading conditions. Conclusions: SG can reduce the maximum stress in the vertebra and intervertebral discs, offering better biomechanical performance and improved stability than IG.

Beyond the promise: Exploring the complex interactions of nanoparticles within biological systems.

The exploration of nanoparticle applications is filled with promise, but their impact on the environment and human health raises growing concerns. These tiny environmental particles can enter the human body through various routes, such as the respiratory system, digestive tract, skin absorption, intravenous injection, and implantation. Once inside, they can travel to distant organs via the bloodstream and lymphatic system. This journey often results in nanoparticles adhering to cell surfaces and being internalized. Upon entering cells, nanoparticles can provoke significant structural and functional changes. They can potentially disrupt critical cellular processes, including damaging cell membranes and cytoskeletons, impairing mitochondrial function, altering nuclear structures, and inhibiting ion channels. These disruptions can lead to widespread alterations by interfering with complex cellular signaling pathways, potentially causing cellular, organ, and systemic impairments. This article delves into the factors influencing how nanoparticles behave in biological systems. These factors include the nanoparticles' size, shape, charge, and chemical composition, as well as the characteristics of the cells and their surrounding environment. It also provides an overview of the impact of nanoparticles on cells, organs, and physiological systems and discusses possible mechanisms behind these adverse effects. Understanding the toxic effects of nanoparticles on physiological systems is crucial for developing safer, more effective nanoparticle-based technologies.

Emission and spatial variation characteristics of odorous pollutants in the aerobic tank of an underground wastewater treatment plant (UWWTP) in southern China.

In this study, the spatial concentration of odorous pollutants in the aerobic tank of an underground wastewater treatment plant (UWWTP) in southern China is monitored. The odour activity value, odour contribution rate, and chemical concentration contribution rate are used to evaluate the degree of contribution of odorous substances. Computational fluid dynamics (CFD) simulations of odorous pollutant diffusion are also established. The study shows that the odorous substances detected in the aerobic tank mainly included ammonia (NH3), hydrogen sulfide (H2S), trimethylamine (C3H9N), and methanethiol (CH3SH), and their concentrations are 1.160, 0.778, 0.022, and 0.0006 mg/m3, respectively. The total odour activity value of the aerobic tank is 450.72 (dimensionless), of which the odour activity value of H2S is 432.22, and the contribution rate reaches 95.9%. H2S is the main contributor to odour and a key controlled substance. The air inlets and exhaust outlets in the aerobic tank are cross-arranged at the top of the space, and the CFD model of odorous pollutant diffusion shows that the gas flow organization determines the odorous pollutant diffusion. The spatial distribution of gas flow and odorous substances in the aerobic tank is relatively uniform, and the odour collection efficiency is higher. The production flux and production coefficient of H2S in the aerobic tank are calculated as 25.831 mg/(m2·h) and 14.149 mg/t, respectively. This study determines the reasonable air supply and exhaust design of the aerobic tank, the number of odour pollutants, and the key controlled substances. These findings offer guidance and serve as useful references for the prevention and control of odour pollution in aerobic tanks of the same type of UWWTPs.

Self-assembled coating with a metal-polyphenolic network for intraocular lens modification to prevent posterior capsule opacification.

Posterior capsule opacification (PCO) is a main complication after cataract surgery and intraocular lens (IOLs) implantation and is attributed to residual lens epithelial cells (LECs) migrating to the IOL surface and posterior capsules. IOL surface modification has been a newly-developing research filed in recent years; however, the applicability and economical acquisition of modified materials remain unsolved. In this study, we first applied a metal-polyphenolic network coating with a self-assembly technique on the IOL surface by using tannic acid (TA) combined with AlCl3, which are easily acquire and applying on the IOL surface to solve the IOL transmittance affair. Using wound healing and Transwell assay to verify AZD0364 inhibits cell migration (P< 0.05), the lipopolysaccharide-induced macrophage inflammation model to verify pterostilbene (PTE) inhibits the inflammatory reaction (P< 0.01). By optimizes its self-assembly coating parameters and calculating its drug release kinetics, we successfully loaded these two drugs on the coating, named TA (AZD0364/PTE) IOL. Its surface morphology characteristics were analyzed by scanning electron microscope, x-ray photoelectron spectrometer and water contact angle. The optical performance was carefully investigated by optical instruments and equipment (n= 3). Thein vitroresults showed that TA (AZD0364/PTE) IOL can significantly inhibit cell adhesion and acute inflammation (n= 3,P< 0.0001). Importantly, afterin vivoimplantation for 28 d with eight rabbits PCO models in two groups, the TA (AZD0364/PTE) IOL group maintained clear refracting media and decreased the inflammatory reaction compared with the original IOL group (P< 0.05). This study provides a new applicable and economical strategy for preventing PCO and offers a reference for the next generation of IOLs that benefit cataract patients.

Erchen decoction alleviates the progression of NAFLD by inhibiting lipid accumulation and iron overload through Caveolin-1 signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: A combination of 6 different Chinese herbs known as Erchen decoction (ECD) has been traditionally used to treat digestive tract diseases and found to have a protective effect against nonalcoholic fatty liver disease (NAFLD). Despite its efficacy in treating NAFLD, the precise molecular mechanism by which Erchen Decoction regulated iron ion metabolism to prevent disease progression remained poorly understood. AIM OF STUDY: Our study attempted to confirm the specific mechanism of ECD in reducing lipid and iron in NAFLD from the perspective of regulating the expression of Caveolin-1 (Cav-1). STUDY DESIGN: In our study, the protective effect of ECD was investigated in Palmitic Acid + Oleic Acid-induced hepatocyte NAFLD model and high-fat diet-induced mice NAFLD model. To investigate the impact of Erchen Decoction (ECD) on lipid metabolism and iron metabolism via mediating Cav-1 in vitro, Cav-1 knockdown cell lines were established using lentivirus-mediated transfection techniques. MATERIALS AND METHODS: We constructed NAFLD model by feeding with high-fat diet for 12 weeks in vivo and Palmitic Acid + Oleic Acid treatment for 24 h in vitro. The regulation of Lipid and iron metabolism results by ECD were detected by serological diagnosis, immunofluorescent and immunohistochemical staining, and western blotting. The binding ability of 6 small molecules of ECD to Cav-1 was analyzed by molecular docking. RESULTS: We demonstrated that ECD alleviated the progression of NAFLD by inhibiting lipid accumulation, nitrogen oxygen stress, and iron accumulation in vivo and in vitro experiments. Furthermore, ECD inhibited lipid and iron accumulation in liver by up-regulating the expression of Cav-1, which indicated that Cav-1 was an important target for ECD to exert its curative effect. CONCLUSIONS: In summary, our study demonstrated that ECD alleviated the accumulation of lipid and iron in NAFLD through promoting the expression of Cav-1, and ECD might serve as a novel Cav-1 agonist to treat NAFLD.

Comparative Analysis of Therapeutic Outcomes Between Modified Loop Plate and Hook Plate for Treating Acute Acromioclavicular Joint Dislocation.

Objective: This study aimed to evaluate the clinical efficacy of an enhanced minimally invasive NICE joint technique combined with dual adjustable loop steel plate internal fixation for treating acute acromioclavicular joint dislocation. Methods: A retrospective analysis was conducted on 63 surgical patients treated with acute acromioclavicular joint dislocation from May 2017 to March 2022. Among them, 33 cases were treated with the clavicle hook plate, and 30 cases were treated with the minimally invasive loop plate. We compared hospitalization duration, incision length, surgical duration, intraoperative bleeding, visual analogue pain scale scores, shoulder joint Constant scores at 6 months before and after surgery, and the incidence of complications between the two groups. Results: The comparison between the two groups, including hospitalization duration, incision length, surgical duration, intraoperative bleeding volume, and shoulder joint Constant score at 6 months post-surgery, revealed statistically significant differences where the loop plate group had better results. One case (1/33) experienced postoperative complications in the hook plate group, including screw loosening and plate failure. Additionally, there were 8 cases (8/33) of subacromial osteolysis, 10 cases (10/33) of acromial impact, and 5 cases (5/33) of residual shoulder pain. Conversely, only 1 case (1/30) in the loop plate group had residual shoulder pain. Conclusions: The surgical technique involving the reconstruction of the coracoclavicular ligament using an enhanced minimally invasive NICE junction combined with double adjustable loop steel plate placement in the clavicular small bone canal is characterized by simplicity, safety, minimal invasiveness, excellent functional recovery, fewer complications, and superior clinical efficacy compared to clavicular hook steel plates.

Ultralow-background SERS substrates for reliable identification of organic pollutants and degradation intermediates.

Chemical methods for preparing SERS substrates have the advantages of low cost and high productivity, but the strong background signals from the substrate greatly limit their applications in characterization and identification of organic compounds. Herein, we developed a one-step synthesis method to prepare silver nanoparticle substrates with ultralow SERS background using anionic ligands as stabilizing agents and applied the SERS substrate for the reliable and reproducible identification of typical organic pollutants and corresponding degradation intermediates. The synthesis method shows excellent universality to different reducing agents cooperating with different anionic ligands (Cl-, Br-, I-, SCN-). As model applications, the machine learning algorithm can realize the precise prediction of six organophosphorus pesticides and eight sulfonamide antibiotics with 100% accuracy based on SERS training data. More importantly, the ultralow-background SERS substrate enables one to detect and identify the time-dependent degradation intermediates of organophosphorus pesticides by combining them with density functional theory (DFT) calculations. All the results indicate that the ultralow-background SERS substrate will greatly push the development of SERS characterization applications.

Prediction of hip joint function and analysis of risk factors for internal fixation failure after Femoral Neck System (FNS).

OBJECTIVE: Analysis of the risk factors affecting hip function and complications after femoral neck system (FNS) surgery for femoral neck fractures is of great significance for improving the procedure's efficacy. METHODS: The data of patients with femoral neck fractures who underwent FNS surgery in our hospital between October 2019 and October 2020 were retrospectively analyzed. Age, gender, time from injury to operation, fracture classification, operation time, fracture reduction, and postoperative weight-bearing time information were set as potential factors that may affect the results. Hip Harris scores were performed at 12 months postoperatively, and postoperative complication data (e.g., femoral head necrosis, nonunion, and femoral neck shortness) were collected. The risk factors affecting hip function and complications after FNS surgery were predicted using linear and logistic regression analyses. RESULTS: A total of 69 cases of femoral neck fracture were included, with an average age of 56.09 ± 11.50 years. The linear analysis demonstrated that the age and fracture type of the patients were the risk factors affecting the Harris score of the hip joint after FNS surgery. Older patients with displaced femoral neck fractures had an inferior postoperative hip function. In addition, fracture type, reduction of the femoral neck, and postoperative weight-bearing significantly impacted postoperative complications. Displaced fractures, negative fixation, and premature weight-bearing (< 6 weeks) were risk factors for postoperative complications. The Harris score of patients with a shortened femoral neck in the included cases was not significantly different from that of patients without shortening (P = 0.25). CONCLUSIONS: Advanced age and fracture type are important evaluation indicators of the Harris score after FNS internal fixation of femoral neck fractures in young patients. Fracture type, fracture reduction, and postoperative weight-bearing time are risk factors for complications after FNS.

Tough, adhesive biomimetic hyaluronic acid methacryloyl hydrogels for effective wound healing.

The development of cost-effective, biocompatible soft wound dressings is highly desirable; however, conventional dressings are only designed for flat wounds, which creates difficulty with promising healing efficiency in complex practical conditions. Herein, we developed a tough, adhesive biomimetic hyaluronic acid methacryloyl hydrogels composed of chemically crosslinked hyaluronic acid methacryloyl (HAMA) network and poly(N-hydroxyethyl acrylamide) (PHEAA) network rich in multiple hydrogen bonding. Due to the multiple chemical crosslinking sites (acrylamide groups) of HAMA; the bulk HEMA/PHEAA hydrogels presented significant enhancements in mechanical properties (∼0.45 MPa) than common hyaluronic acid hydrogels (<0.1 MPa). The abundant hydrogen bonding also endowed the resultant hydrogels with extremely high adhesiveness on many nonporous substrates, including glass and biological tissues (e.g., heart, liver, lung, kidney, stomach, and muscle), with a considerable interfacial toughness of ∼1432 J m-2. Accordingly, since both natural hyaluronic acid derivative polymers and hydrophilic PHEAA networks are highly biocompatible, the hydrogel matrix possesses good blood compatibility (<5% of hemolysis ratio) and satisfies the general dressing requirements (>99% of cell viability). Based on these physicochemical features, we have demonstrated that this adhesive hydrogel, administered in the form of a designed patch, could be applied to wound tissue healing by promoting epithelialization, angiogenesis, and collagen deposition. We believe that our proposed biomimetic hydrogel design holds great potential for wound repair and our developed HAMA/PHEAA hydrogels are extremely promising for the next-generation tissue healings in emergency situations.

Feasibility Analysis of the Bone Cement-Gelatine Sponge Composite Intravertebral Prefilling Technique for Reducing Bone Cement Leakage in Stage I and II Kümmell's Disease: A Prospective Randomized Controlled Trial.

OBJECTIVE: Bone cement leakage is a major complication of percutaneous vertebroplasty (PVP) while treating Kümmell's disease and it is a focus of close attention during the surgical procedure. The study aimed to investigate whether pre-injecting a composite of bone cement and gelatine sponge (the "bone cement-gelatine sponge composite") before injecting bone cement during PVP aids in lowering the leakage rate in stage I and II Kümmell's disease. METHODS: This prospective analysis evaluated 74 patients with stage I and II Kümmell's disease who underwent PVP treatment at our hospital from December 2019 to December 2021. The participants were divided randomly into groups based on whether the bone cement-gelatine sponge composite was used during the surgery. The two groups were the bone cement-gelatine sponge composite group (GS group, comprising 37 patients) and the no bone cement-gelatine sponge composite group (N-GS group, comprising 37 patients). The independent samples t-test and chi-square test were employed to compare general information, operative time, cement injection volume, intraoperative bleeding, and bone cement leakage between the two groups. Additionally, the visual analogue scale (VAS) score, Oswestry disability index (ODI), anterior vertebral height ratio (AVHR), and the kyphotic Cobb angle were compared between the two groups at the preoperative, 2 days postoperative, and 6 months postoperative stages using repeated measures analysis of variance. RESULTS: All patients were followed up for more than 6 months, with an average of (11.19 ± 2.21) months. No significant differences were observed in terms of the operative time, cement injection volume, and intraoperative bleeding between the two groups (P > 0.05). The incidence of bone cement leakage in the N-GS group (32.43%) was significantly higher than that in the GS group (5.41%), and the difference was statistically significant (P < 0.05). The VAS score and ODI of the two groups at postoperative 2 days and 6 months improved significantly (P < 0.05). The AVHR and kyphotic Cobb angle were corrected to a certain extent (P < 0.05); however, no significant difference was observed between the two groups (P > 0.05). CONCLUSION: The bone cement-gelatine sponge composite intravertebral prefilling technique can lower bone cement leakage in stage I and II Kümmell's disease and can also relieve pain and improve vertebral body height.

Metformin sensitises osteosarcoma to chemotherapy via the IGF-1R/miR-610/FEN1 pathway.

Metformin can enhance cancer cell chemosensitivity to anticancer drugs. IGF-1R is involved in cancer chemoresistance. The current study aimed to elucidate the role of metformin in osteosarcoma (OS) cell chemosensitivity modulation and identify its underlying mechanism in IGF-1R/miR-610/FEN1 signalling. IGF-1R, miR-610, and FEN1 were aberrantly expressed in OS and participated in apoptosis modulation; this effect was abated by metformin treatment. Luciferase reporter assays confirmed that FEN1 is a direct target of miR-610. Moreover, metformin treatment decreased IGF-1R and FEN1 but elevated miR-610 expression. Metformin sensitised OS cells to cytotoxic agents, while FEN1 overexpression partly compromised metformin's sensitising effects. Furthermore, metformin was observed to enhance adriamycin's effects in a murine xenograft model. Metformin enhanced OS cell sensitivity to cytotoxic agents via the IGF-1R/miR-610/FEN1 signalling axis, highlighting its potential as an adjuvant during chemotherapy.

Correlation analysis of larger side bone cement volume/vertebral body volume ratio with adjacent vertebral compression fractures during vertebroplasty.

Objective: To investigate the correlation analysis of larger side bone cement volume/vertebral body volume ratio (LSBCV/VBV%) with adjacent vertebral compression fracture (AVCF) in percutaneous vertebroplasty (PVP) for osteoporotic vertebral compression fracture (OVCF). Methods: A retrospective analysis of 245 OVCF patients who underwent PVP treatment from February 2017 to February 2021, including 85 males and 160 females. The age ranged from 60 to 92 years, with a mean of (70.72 ± 7.03) years. According to whether AVCF occurred after surgery, they were divided into 38 cases in the AVCF group (fracture group) and 207 cases in the no AVCF group (non-fracture group). The correlation between gender, age, bone mineral density (BMD), body mass index (BMI), thoracolumbar segment fracture, bone cement disc leakage, LSBCV, bone cement volume (BCV), VBV, LSBCV/VBV ratio (LSBCV/VBV%), and BCV/VBV% and AVCF were analyzed in both groups. Risk factors for AVCF after PVP were analyzed by multifactorial logistic regression, and then the receiver operating characteristic curves (ROC curves) were plotted to identify the critical value of LSBCV/VBV%. Results: 38 patients (15.5%) developed AVCF postoperatively. Univariate analysis showed that BMD, bone cement disc leakage, LSBCV, and LSBCV/VBV% were risk factors for AVCF after PVP (P<0.05), while gender, age, BMI, thoracolumbar segment fracture, BCV, VBV, and BCV/VBV% were not significantly different in both groups (P>0.05). Multifactorial logistic regression analysis revealed that BMD, bone cement disc leakage, and LSBCV/VBV% were independent risk factors for AVCF after PVP (P<0.05). According to the ROC curve, the LSBCV/VBV% had an area under the curve of 71.6%, a sensitivity and specificity of 89.5% and 51.7%, respectively, and a critical value of 13.82%. Conclusion: BMD, bone cement disc leakage and LSBCV/VBV% are independent risk factors for AVCF after PVP. With LSBCV/VBV at 13.82%, the incidence of AVCF significantly increased.

Synthetic biology for plant genetic engineering and molecular farming.

Many efforts have been put into engineering plants to improve crop yields and stress tolerance and boost the bioproduction of valuable molecules. Yet, our capabilities are still limited due to the lack of well-characterized genetic building blocks and resources for precise manipulation and given the inherently challenging properties of plant tissues. Advancements in plant synthetic biology can overcome these bottlenecks and release the full potential of engineered plants. In this review, we first discuss the recently developed plant synthetic elements from single parts to advanced circuits, software, and hardware tools expediting the engineering cycle. Next, we survey the advancements in plant biotechnology enabled by these recent resources. We conclude the review with outstanding challenges and future directions of plant synthetic biology.

Comparison of femoral neck system and three cannulated cancellous screws in the treatment of vertical femoral neck fractures: clinical observation and finite element analysis.

OBJECTIVE: The purpose of this study was to compare the biomechanical and clinical results of two surgical methods for the treatment of vertical femoral neck fractures: Femoral neck system (FNS) and traditional three cannulated cancellous screws (CCS). METHODS: First, we developed three different vertical femoral neck fracture models for the finite element analysis, with angles of 55°, 65°, and 75°, respectively. Two experimental groups were set up: the FNS group and the CCS group. Each fracture group was tested under axial loads of 2100 N to measure the femur's displacement, Von Mises stress (VMS), and its internal fixation components. Secondly, we retrospectively included the cases of vertical femoral neck fractures with FNS and CCS in our hospital from May 2019 to May 2021. In this study, we compared the duration of intraoperative fluoroscopy, operative time, hospital stay, fracture healing time, Hemoglobin loss, Harris score of hip joint function, and postoperative complications among patients undergoing hip joint replacement. RESULTS: In terms of finite element analysis, FNS has better anti-displacement stability than CCS at 55°and 65°, while FNS is greater than CCS in Von Mises stress. Clinically, we followed up on 87 patients for an average of 12 months. FNS was superior to traditional CCS in fracture healing time, operation time, fluoroscopy duration, fracture healing time, and Harris hip function score. CONCLUSION: FNS is superior to traditional CCS in biomechanical and clinical aspects of treating vertical femoral neck fractures. There is potential for FNS to become a new treatment option for vertical femoral neck fractures.

HNF4A Negatively Regulated Posterior Capsular Opacification via Transcriptional Inhibition of MMP2.

PURPOSE: Posterior capsular opacification is the most common complication after cataract surgery. Abnormal proliferation, migration, epithelial-mesenchymal transition, and extracellular matrix synthesis of residual lens epithelial cells are considered to be the main pathogenic mechanisms. Hepatocyte nuclear factor 4α has been reported to regulate epithelial-mesenchymal transition in different tumors. Our objective was to investigate the role and mechanism of hepatocyte nuclear factor 4α in posterior capsular opacification. METHODS: Hepatocyte nuclear factor 4α expression was tested in posterior capsular opacification rat lens capsules and cell models. Hepatocyte nuclear factor 4α was knocked down using small hairpin RNA. Cell viability was measured by Cell Counting Kit-8 assay. Cell migration ability was evaluated by wound healing and Transwell assays. Epithelial-mesenchymal transition markers were detected by Western blotting. Transcriptome sequencing was used to screen for downstream effectors of hepatocyte nuclear factor 4α. Chromatin immunoprecipitation and a dual luciferase reporter assay were used to determine the binding of hepatocyte nuclear factor 4α to the MMP2 promoter region. RESULTS: Hepatocyte nuclear factor 4α was downregulated in posterior capsular opacification tissue and cell models. In vitro studies showed that hepatocyte nuclear factor 4α deletion facilitated cell proliferation, migration, and epithelial-mesenchymal transition protein marker expression in lens epithelial cells. Hepatocyte nuclear factor 4α knockdown promoted epithelial-mesenchymal transition and migration of lens epithelial cells via MMP2. Mechanistically, hepatocyte nuclear factor 4α decreased MMP2 expression by binding to the MMP2 promoter region. Hepatocyte nuclear factor 4α deletion also promoted epithelial-mesenchymal transition in rat lens capsules. CONCLUSIONS: We demonstrated that hepatocyte nuclear factor 4α inhibited epithelial-mesenchymal transition of lens epithelial cells by directly binding to the MMP2 promoter region and inhibiting the expression of MMP2, thus leading to retardation of posterior capsular opacification formation and development, suggesting that hepatocyte nuclear factor 4α is a potential therapeutic target for posterior capsular opacification.