Microfluidic fabrication of monodisperse microcapsules with gas cores.

A facile strategy for efficient and continuous fabrication of monodisperse gas-core microcapsules with controllable sizes and excellent ultrasound-induced burst performances is developed based on droplet microfluidics and interfacial polymerization. Monodisperse gas-in-oil-in-water (G/O/W) double emulsion droplets with a gas core and monomer-contained oil layer are fabricated in the upstream of a microfluidic device as templates, and then water-soluble monomers are added into the aqueous continuous phase in the downstream to initiate rapid interfacial polymerization at the O/W interfaces to prepare monodisperse gas-in-oil-in-solid (G/O/S) microcapsules with gas cores. The sizes of both microbubbles and G/O/W droplet templates can be precisely controlled by adjusting the gas supply pressure and the fluid flow rates. Due to the very thin shells of G/O/S microcapsules fabricated via interfacial polymerization, the sizes of the resultant G/O/S microcapsules are almost the same as those of the G/O/W droplet templates, and the microcapsules exhibit excellent deformable properties and ultrasound-induced burst performances. The proposed strategy provides a facile and efficient route for controllably and continuously fabricating monodisperse microcapsules with gas cores, which are highly desired for biomedical applications.

High-throughput screening carbon and nitrogen sources to promote growth and sporulation in Rhizopus arrhizus.

Rhizopus arrhizus is a saprotrophic, sometimes clinically- and industrially-relevant mold (Mucorales) and distributed worldwide, suggesting it can assimilate a broad spectrum of substrates. Here, 69 strains of R. arrhizus were investigated by using the Biolog FF MicroPlate for the profiles of utilizing 95 carbon and nitrogen substrates. The study showed that most R. arrhizus strains were similar in average well color development (AWCD) and substrate richness (SR). Nevertheless, 13 strains were unique in principal component analyses, heatmap, AWCD, and SR analyses, which may imply a niche differentiation within R. arrhizus. The species R. arrhizus was able to utilize all the 95 carbon and nitrogen substrates, consistent with the hypothesis of a great metabolic diversity. It possessed a substrate preference of alcohols, and seven substrates were most frequently utilized, with N-acetyl-D-galactosamine and L-phenylalanine ranking at the top of the list. Eight substrates, especially L-arabinose and xylitol, were capable of promoting sporulation and being applied for rejuvenating degenerated strains. By phenotyping R. arrhizus strains in carbon and nitrogen assimilation capacity, this study revealed the extent of intra-specific variability and laid a foundation for estimating optimum substrates that may be useful for industrial applications.

AOB Nitrosospira cluster 3a.2 (D11) dominates N2O emissions in fertilised agricultural soils.

Ammonia-oxidation process directly contribute to soil nitrous oxide (N2O) emissions in agricultural soils. However, taxonomy of the key nitrifiers (within ammonia oxidising bacteria (AOB), archaea (AOA) and complete ammonia oxidisers (comammox Nitrospira)) responsible for substantial N2O emissions in agricultural soils is unknown, as is their regulation by soil biotic and abiotic factors. In this study, cumulative N2O emissions, nitrification rates, abundance and community structure of nitrifiers were investigated in 16 agricultural soils from major crop production regions of China using microcosm experiments with amended nitrogen (N) supplemented or not with a nitrification inhibitor (nitrapyrin). Key nitrifier groups involved in N2O emissions were identified by comparative analyses of the different treatments, combining sequencing and random forest analyses. Soil cumulative N2O emissions significantly increased with soil pH in all agricultural soils. However, they decreased with soil organic carbon (SOC) in alkaline soils. Nitrapyrin significantly inhibited soil cumulative N2O emissions and AOB growth, with a significant inhibition of the AOB Nitrosospira cluster 3a.2 (D11) abundance. One Nitrosospira multiformis-like OTU phylotype (OTU34), which was classified within the AOB Nitrosospira cluster 3a.2 (D11), had the greatest importance on cumulative N2O emissions and its growth significantly depended on soil pH and SOC contents, with higher growth at high pH and low SOC conditions. Collectively, our results demonstrate that alkaline soils with low SOC contents have high N2O emissions, which were mainly driven by AOB Nitrosospira cluster 3a.2 (D11). Nitrapyrin can efficiently reduce nitrification-related N2O emissions by inhibiting the activity of AOB Nitrosospira cluster 3a.2 (D11). This study advances our understanding of key nitrifiers responsible for high N2O emissions in agricultural soils and their controlling factors, and provides vital knowledge for N2O emission mitigation in agricultural ecosystems.

Concomitant double-fusion of PLEKHA7-ALK and INPP5D-ALK reveals favorable alectinib sensitivity in lung adenocarcinoma: a case report and literature review.

Anaplastic lymphoma kinase (ALK) gene fusion is a classic driver mutation in non-small cell lung cancer (NSCLC); however, ALK double-fusion variants in NSCLC have rarely been reported. In this study, we reported a case with extremely uncommon ALK double-fusion variants. A 32-year-old female diagnosed with lung adenocarcinoma, who had developed multiple intrapulmonary and brain metastases, experienced worsening of her condition despite undergoing prior chemotherapy. Subsequent testing using next-generation sequencing (NGS) detected the presence of PLEKHA7-ALK and INPP5D-ALK double-fusion. The prescription of alectinib revealed potent efficacy and resulted in an increase in the survival rate. This case presented two uncommon and concomitant ALK fusion partners in NSCLC; more importantly, the INPP5D-ALK subtype has not been reported, therefore this study broadens the spectrum of ALK double-fusion variants and provides insight into the use of ALK inhibitors for the treatment of NSCLC in patients with double ALK fusions.

Dissolving microneedle system containing Ag nanoparticle-decorated silk fibroin microspheres and antibiotics for synergistic therapy of bacterial biofilm infection.

Most cases of delayed wound healing are associated with bacterial biofilm infections due to high antibiotic resistance. To improve patient compliance and recovery rates, it is critical to develop minimally invasive and efficient methods to eliminate bacterial biofilms as an alternative to clinical debridement techniques. Herein, we develop a dissolving microneedle system containing Ag nanoparticles (AgNPs)-decorated silk fibroin microspheres (SFM-AgNPs) and antibiotics for synergistic treatment of bacterial biofilm infection. Silk fibroin microspheres (SFM) are controllably prepared in an incompatible system formed by a mixture of protein and carbohydrate solutions by using a mild all-aqueous phase method and serve as biological templates for the synthesis of AgNPs. The SFM-AgNPs exert dose- and time-dependent broad-spectrum antibacterial effects by inducing bacterial adhesion. The combination of SFM-AgNPs with antibiotics breaks the limitation of the antibacterial spectrum and achieves better efficacy with reduced antibiotic dosage. Using hyaluronic acid (HA) as the soluble matrix, the microneedle system containing SFM-AgNPs and anti-Gram-positive coccus drug (Mupirocin) inserts into the bacterial biofilms with sufficient strength, thereby effectively delivering the antibacterial agents and realizing good antibiofilm effect on Staphylococcus aureus-infected wounds. This work demonstrates the great potential for the development of novel therapeutic systems for eradicating bacterial biofilm infections.

FAFuse: A Four-Axis Fusion framework of CNN and Transformer for medical image segmentation.

Medical image segmentation is crucial for accurate diagnosis and treatment in the medical field. In recent years, convolutional neural networks (CNNs) and Transformers have been frequently adopted as network architectures in medical image segmentation. The convolution operation is limited in modeling long-range dependencies because it can only extract local information through the limited receptive field. In comparison, Transformers demonstrate excellent capability in modeling long-range dependencies but are less effective in capturing local information. Hence, effectively modeling long-range dependencies while preserving local information is essential for accurate medical image segmentation. In this paper, we propose a four-axis fusion framework called FAFuse, which can exploit the advantages of CNN and Transformer. As the core component of our FAFuse, a Four-Axis Fusion module (FAF) is proposed to efficiently fuse global and local information. FAF combines Four-Axis attention (height, width, main diagonal, and counter diagonal axial attention), a multi-scale convolution, and a residual structure with a depth-separable convolution and a Hadamard product. Furthermore, we also introduce deep supervision to enhance gradient flow and improve overall performance. Our approach achieves state-of-the-art segmentation accuracy on three publicly available medical image segmentation datasets. The code is available at https://github.com/cczu-xiao/FAFuse.

Microfluidic Controllable Preparation of Iodine-131-Labeled Microspheres for Radioembolization Therapy of Liver Tumors.

Transcatheter arterial radioembolization (TARE) is of great significance for the treatment of advanced hepatocellular carcinoma (HCC). However, the existing radioembolic microspheres still have problems such as non-degradability, non-uniform size, and inability to directly monitor in vivo, which hinders the development of TARE. In this paper, a novel radioembolic agent, 131 I-labeled methacrylated gelatin microspheres (131 I-GMs), is prepared for the treatment of HCC. Water-in-oil (W/O) emulsion templates are prepared by a simple one-step microfluidic method to obtain methacrylated gelatin microspheres (GMs) after UV irradiation. A series of GMs with uniform and controllable size is obtained by adjusting the flow rate of each fluid. Both air-dried and freeze-dried GMs can quickly restore their original shape and size, and still have good monodispersity, elasticity, and biocompatibility. The radiolabeling experiments show that 131 I can efficiently bind to GMs by chloramine-T method, and the obtained 131 I-GMs have good radioactive stability in vitro. The results of in vivo TARE treatment in rats show that 131 I-GMs can be well retained in the hepatic artery and have a good inhibitory effect on the progression of liver cancer, showing the potential for the treatment of HCC.

Optimum fractionation of radiation to combine PD-1 blockade.

The optimum fractionation of radiation to combine with immune checkpoint blockade is controversial. This study aimed to investigate the fractionated radiation to maximize immunity during combination therapy. To evaluate the abscopal effect, C57BL/6 hPD-1 knock-in mice bearing two syngeneic contralateral MC38 murine colon cancer tumors were treated with four distinct regimens of radiotherapy. Three fractions of 8 Gy were chosen as the optimal fractionation to combine with anti-PD-1 as the optimal fractionation for maximizing immunity. Anti-PD-1 administration enhanced both local and systemic antitumor immunity in a cytotoxic T cell-dependent manner. Meanwhile, the spleen exhibited decreased myeloid-derived suppressor cells (MDSCs) under combination treatment. Furthermore, RNA-sequencing revealed significantly increased tumor necrosis factor (TNF) receptors and cytokines associated with lymphocyte infiltration in the combining group. Here we demonstrate that the hypofractionation of 8 Gy × 3f was the optimum-fractionated dosage to maximize immunity, and the combination of anti-PD-1 showed promising results in boosting abscopal effect. Underlying mechanisms may include the activation of T cells and the reduction of MDSCs, which is achieved through the action of TNF and related cytokines. This study indicates a radioimmunotherapy dosage painting method that can be developed to overcome present limitations in tumor immunosuppression.

Novel thermo and ion-responsive copolymers based on metallo-base pair directed host-guest complexation for highly selective recognition of Hg2+ in aqueous solution.

The development of materials with highly selective recognition towards Hg2+ is of great significance in environmental monitoring. Herein, a novel thermo-responsive copolymer with Hg2+ recognition property is prepared via thermally-initiated copolymerization of 5'-O-Acryloyl 5-methyl-uridine (APU) and N-isopropylacrylamide (NIPAM). The chemical structure and stimuli-sensitive properties of poly(N-isopropylacrylamide-co-5-methyl-uridine) (P(NIPAM-co-APU)) linear polymers and hydrogel are thoroughly investigated. At the supramolecular level, P(NIPAM-co-APU) linear polymers could respond to both temperature and Hg2+ stimuli with highly selective recognition towards Hg2+ over other 18 metal ion species (at least 5 fold difference) and common anions. Upon capturing Hg2+ by APU units as host metal receptors, the lower critical solution temperature (LCST) of P(NIPAM-co-APU, PNU-7 and PNU-11) linear polymers are significantly shifted more than 10 °C due to the formation of stable APU-Hg2+-APU directed host-guest complexes. Accordingly, at the macroscopic level, P(NIPAM-co-APU) hydrogel display selective and robust recognition of Hg2+ under optimum conditions, and its maximum Hg2+ uptake capacity was 33.1 mg g-1. This work provides a new option for Hg2+ recognition with high selectivity, which could be facilely integrated with other smart systems to achieve satisfactory detection of environmental Hg2+.

Relationship between the Depth of Acetabuloplasty and Outcomes of Hip Arthroscopy in Patients with Global Pincer Femoroacetabular Impingement: Study with a Minimum Follow-Up Period of 2 Years.

OBJECTIVE: There has been no definite consensus on the ideal depth of acetabuloplasty, especially in cases of global pincer femoroacetabular impingement (FAI). This study aims to determine whether the depth of acetabuloplasty influences postoperative outcomes in cases of global pincer FAI. METHODS: Data were retrospectively collected from patients with global pincer FAI who underwent hip arthroscopy with a minimum follow-up period of 2 years from May 2014 to December 2018. Patients with global pincer FAI were subdivided into low or high resection depth groups based on whether the intraoperative acetabular rim was resected by more than 3 mm. Radiographic measurements; arthroscopic procedures; preoperative and postoperative PROs were recorded. Achievement of MCID and PASS was compared for the VAS, mHHS, HOS-ADL, and iHOT-12. A paired Student t-test was used to evaluate the significance of preoperative and postoperative PROs and two-tailed unpaired Student t-test was used to compare demographic data and PROs between different groups. MCID and PASS were evaluated using the chi-square test or the Fisher's exact test. RESULTS: A total of 41 hips with global pincer FAI (15 and 26 patients in low or high resection depth groups, respectively) were included in this study. Both groups showed significant postoperative improvements in the scores of all PROs (p < 0.001). Compared to the low resection depth group, the high resection depth group had a lower degree of improvement through hip arthroscopy, which manifested as lower postoperative mHHS scores (94.29 vs. 85.08, p = 0.006), higher VAS scores (0.93 vs. 2.54, p = 0.002), and lower improvements in VAS (-5.00 vs. -3.35, p = 0.028), HOS-ADL (34.99 vs. 23.90, p = 0.017) and iHOT-12 (39.89 vs. 29.27, p = 0.036). Patients in high resection depth group were less likely to achieve the MCID for the VAS score compared to low resection depth group in significant (73.3 vs. 26.9%, p = 0.004). CONCLUSIONS: For patients with global pincer, the outcomes in high resection depth group were slightly worse than the the low resection depth group. It is indicated that excessive resection of the acetabular rim during the procedure should be avoided.

Controllable Fabrication of Highly Uniform Sub-10 nm Nanoparticles from Spontaneous Confined Nanoemulsification.

Sub-10 nm nanoparticles are known to exhibit extraordinary size-dependent properties for wide applications. Many approaches have been developed for synthesizing sub-10 nm inorganic nanoparticles, but the fabrication of sub-10 nm polymeric nanoparticles is still challenging. Here, a scalable, spontaneous confined nanoemulsification strategy that produces uniform sub-10 nm nanodroplets for template synthesis of sub-10 nm polymeric nanoparticles is proposed. This strategy introduces a high-concentration interfacial reaction to create overpopulated surfactants that are insoluble at the droplet surface. These overpopulated surfactants act as barriers, resulting in highly accumulated surfactants inside the droplet via a confined reaction. These surfactants exhibit significantly changed packing geometry, solubility, and interfacial activity to enhance the molecular-level impact on interfacial instability for creating sub-10 nm nanoemulsions via self-burst nanoemulsification. Using the nanodroplets as templates, the fabrication of uniform sub-10 nm polymeric nanoparticles, as small as 3.5 nm, made from biocompatible polymers and capable of efficient drug encapsulation is demonstrated. This work opens up brand-new opportunities to easily create sub-10 nm nanoemulsions and advanced ultrasmall functional nanoparticles.

Novel Double-Layer Dissolving Microneedles for Transmucosal Sequential Delivery of Multiple Drugs in the Treatment of Oral Mucosa Diseases.

The development of transmucosal drug delivery systems is a practical requirement in oral clinical practice, and controlled sequential delivery of multiple drugs is usually required. On the basis of the previous successful construction of monolayer microneedles (MNs) for transmucosal drug delivery, we designed transmucosal double-layer sequential dissolving MNs using hyaluronic acid methacryloyl (HAMA), hyaluronic acid (HA), and polyvinyl pyrrolidone (PVP). MNs have the advantages of small size, easy operation, good strength, rapid dissolution, and one-time delivery of two drugs. Morphological test results showed that the HAMA-HA-PVP MNs were small and intact in structure. The mechanical strength and mucosal insertion test results indicated the HAMA-HA-PVP MNs had appropriate strength and could penetrate the mucosal cuticle quickly to achieve transmucosal drug delivery. The in vitro and in vivo experiment results of the double-layer fluorescent dyes simulating drug release revealed that MNs had good solubility and achieved stratified release of the model drugs. The results of the in vivo and in vitro biosafety tests also indicated that the HAMA-HA-PVP MNs were biosafe materials. The therapeutic effect of drug-loaded HAMA-HA-PVP MNs in the rat oral mucosal ulcer model demonstrated that these novel HAMA-HA-PVP MNs quickly penetrated the mucosa, dissolved and effectively released the drug, and achieved sequential drug delivery. Compared to monolayer MNs, these HAMA-HA-PVP MNs can be used as double-layer drug reservoirs for controlled release, effectively releasing the drug in the MN stratification by dissolution in the presence of moisture. The need for secondary or multiple injections can be avoided, thus improving patient compliance. This drug delivery system can serve as an efficient, multipermeable, mucosal, and needle-free alternative for biomedical applications.

Four Patterns of Canine Wei Syndrome Treated with Traditional Chinese Medicine.

Atrophy and weakness of the limbs is a common condition in animals, especially dogs. It typically presents with flaccidity and weakness of the limbs, especially the hind legs, muscle atrophy, and the inability to walk. In Traditional Chinese Medicine (TCM) and Traditional Chinese Veterinary Medicine (TCVM), this is known as wei syndrome (WS). According to TCM, the etiology of WS can be (1) lung heat and fluid consumption; (2) insufficiency of the liver and kidneys; (3) dampness-heat invasion; (4) damage to the spleen and stomach, which are also the patterns of WS. This report aims to provide an alternative option for the treatment of canine paralysis. Four dogs with different WS patterns were treated with acupuncture, moxibustion, and Chinese herbs based on the guidelines of the TCM literature. Three patients recovered normal functioning. The fourth patient could walk normally after 2 weeks of treatment, but his hind limbs became weak again 3 months later. Weekly acupuncture treatment was resumed until his death 18 months later. TCM application of acupuncture, moxibustion, and Chinese herbs can be an effective treatment for canine WS. It is hoped that this case report will broaden the treatment options of other veterinarians when patients present with this condition.

Ultrasensitive hydrogel grating detector for real-time continuous-flow detection of trace threat Pb2.

Ultrasensitive real-time detection of trace Pb2+ in continuous flow is vital to effectively and timely eliminate the potential hazards to ecosystem health and sustainability. This work reports on a micro-structured smart hydrogel grating with ultra-sensitivity, high selectivity, good transparency and mechanical property for real-time detection of Pb2+ in continuous flow. The hydrogel grating possesses uniform surface relief microstructures with periodic nano-height ridges made of poly(acrylamide-co-benzo-18-crown-6-acrylamide) networks that crosslinked by tetra-arm star poly(ethylene glycol)acrylamide. The hydrogel grating with good optical transparency and mechanical property can change its height via selective host-guest complexation with Pb2+ to output a changed diffraction efficiency. Meanwhile, the periodic nano-ridges with large specific area benefit the contact with Pb2+ for fast Pb2+-induced height change. Thus, with such rationally designed molecular structures and surface relief microstructures, the hydrogel grating integrated in a glass-based mini-chip allows real-time detection of Pb2+ in continuous flow with ultra-sensitivity and high selectivity. The hydrogel grating detector can achieve ultralow detection limit (10-9 M Pb2+), fast response (2 min), and selective detection of Pb2+ from dozens of interfering ions even with high concentrations. This high-performance hydrogel grating detector is general and can be extended to detect many analytes due to the wide choice of responsive hydrogels, thus opening new areas for creating advanced smart detectors in analytical science.

Outcomes in Patients with Global Pincer Versus Focal Pincer Femoroacetabular Impingement Treated with Hip Arthroscopy: A Retrospective Study with a Minimum 2-Year Follow-Up.

OBJECTIVE: Global pincer is a relatively rare form of pincer deformity and is typically associated with technical challenges during surgery. So far, controversy remains whether patients with global pincer have equivalent surgical outcomes compared to patients with focal pincer. This study compares the clinical outcomes of arthroscopic treatment between patients with global pincer femoroacetabular impingement (FAI) and focal pincer FAI in the Chinese population. METHODS: Data were retrospectively collected from patients with global and focal pincer FAI who underwent hip arthroscopy with a minimum two-year follow-up between April 2016 and December 2018. Radiographic measurements, arthroscopic procedures, preoperative and postoperative patient-reported outcomes (PROs) including modified Harris hip score (mHHS), hip outcome score-activities of daily living (HOS-ADL), international hip outcome tool-12 (iHOT-12), and visual analogue scale (VAS) scores, rates of revision surgery and conversion to total hip arthroplasty (THA) were recorded. Achievement of minimal clinically important difference (MCID) and patient acceptable symptomatic state (PASS) was compared for the VAS, mHHS, HOS-ADL, and iHOT-12 scores between groups. RESULTS: The total of 33 and 167 patients were included in the global and focal group, respectively. There were no intergroup differences in age, gender, body mass index or follow-up times. Lateral center-edge angle (LCEA) was reduced in both groups postoperatively. Both groups demonstrated significant improvements in PROs compared with preoperative levels at the final follow-up. The preoperative scores showed significant differences in terms of mHHS (60.34 vs 62.90, P = 0.031) and HOS-ADL (61.45 vs 64.74, P = 0.022) scores between two groups, and the improvement of HOS-ADL score was significantly higher in global group (P = 0.027). However, the postoperative scores, including VAS, mHHS, HOS-ADL, and iHOT-12 scores, showed no significant differences between two groups. And there were no significant differences in the rate of meeting the PASS and MCID between groups. One (3.0%) in the global group and six (3.6%) patients in the focal group underwent revision arthroscopy respectively, with no significant difference (P = 0.876). There were no conversions to THA in both groups. CONCLUSIONS: Arthroscopic management of global pincer FAI can achieve excellent functional scores at minimum 2-year follow-up. The outcomes were similar to focal pincer FAI patients with a low rate of secondary procedure.

Composite Separable Microneedles for Transdermal Delivery and Controlled Release of Salmon Calcitonin for Osteoporosis Therapy.

A composite separable microneedles (MNs) system consisting of silk fibroin (SF) needle tips and hyaluronic acid (HA) base is developed for transdermal delivery of salmon calcitonin (sCT) for therapy of osteoporosis. Poly(ethylene glycol) (PEG) is used to modulate the conformation structure of SF to achieve controllable sustained release of sCT. The prepared MNs can effectively penetrate the skin stratum corneum. After application to the skin, the HA base is dissolved within 2 min, allowing these SF drug depots to be implanted into the skin for controllable sustained release of sCT. The release kinetics of sCT can be controlled by regulating the conformation of SF with PEG and the interaction between sCT peptide and SF proteins. Compared with traditional needle injection, delivery of sCT using optimized HA-PEG/SF MNs shows better trabecular bone repair for ovariectomized-induced osteoporosis in mice. The proposed MNs system provides a new noninjection strategy for therapy of osteoporosis.

A comparison between ultrasound-guided AIIS injection and radiography in the diagnosis of subspine impingement in patients with FAI.

BACKGROUND: Subspine impingement (SSI) does not have effective diagnostic criteria, especially in patients who also have femoroacetabular impingement (FAI). The classification of anterior inferior iliac spine (AIIS) morphology via three-dimensional CT is controversial. PURPOSE: To propose a method for ultrasound-guided AIIS injection as a way to diagnose SSI and evaluate the accuracy of radiography methods, including 3-D CT and MRI, as well as intraoperative findings. METHODS: Patients diagnosed with FAI between September 2020 and December 2021 were evaluated in this prospective study. Those who met the criteria were included in the ultrasound-guided AIIS injection test. Whether the pain was relieved after injection was recorded in the radiology report. Patients who experienced significant relief of the anterior groin pain (more than 50%) after the AIIS injection were considered positive responders. Among these patients, radiography materials, including AIIS morphology as measured by 3-D CT as well as superior capsular oedema on MRI, were compared. The presence of congestion or bruising on the capsule side of the labrum corresponding to the AIIS during hip arthroscopy was recorded. RESULTS: A total of 73 patients with FAI underwent the ultrasound-guided AIIS injection test. Prevalence rates of 13.70% (10/73), 58.90% (43/73), 23.29% (17/73) and 4.11% (3/73) were recorded for Type I, Type IIA, Type IIB and Type III AIISs, respectively. Thirty-six patients had positive responses to injection, and 37 patients had negative responses to injection. None of the patients with Type I, 23 (53.49%) patients with Type IIA, 11 (64.71%) patients with Type IIB and 2 (66.7%) patients with Type III AIISs had positive responses to the injection. A total of 57.14% of patients with Type II or Type III AIIS had positive responses to the injection. The proportions of patients with superior capsular oedema on MRI in the Type I, Type IIA, Type IIB, and Type III AIIS groups was 0, 30.23, 29.41 and 0%, respectively. Among non-Type I AIIS patients, those who reported positive responses to the injection had a higher incidence of superior capsular oedema (38.89% vs. 14.81%, P = 0.036), but they had no significant differences in the proportion of congestion or bruising of the labrum (47.22% vs. 37.04%, P = 0.419). The results showed that no pairs of methods-ultrasound-guided injection, MRI, and intraoperative findings-achieved good consistency (κ = 0.222, κ = 0.098 and κ = - 0.116). CONCLUSIONS: Radiographic methods including 3-D CT and MRI as well as the intraoperative findings of the labrum cannot be considered an accurate and reliable basis for the diagnosis and treatment of SSI in FAI patients. It is suggested that ultrasound-guided AIIS injections be combined with radiography to better diagnose SSI. LEVEL OF EVIDENCE: IV, case series.

Designable microfluidic ladder networks from backstepping microflow analysis for mass production of monodisperse microdroplets.

Controllable mass production of monodisperse droplets plays a key role in numerous fields ranging from scientific research to industrial application. Microfluidic ladder networks show great potential in mass production of monodisperse droplets, but their design with uniform microflow distribution remains challenging due to the lack of a rational design strategy. Here an effective design strategy based on backstepping microflow analysis (BMA) is proposed for the rational development of microfluidic ladder networks for mass production of controllable monodisperse microdroplets. The performance of our BMA rule for rational microfluidic ladder network design is demonstrated by using an existing analogism-derived rule that is widely used for the design of microfluidic ladder networks as the control group. The microfluidic ladder network designed by the BMA rule shows a more uniform flow distribution in each branch microchannel than that designed by the existing rule, as confirmed by single-phase flow simulation. Meanwhile, the microfluidic ladder network designed by the BMA rule allows mass production of droplets with higher size monodispersity in a wider window of flow rates and mass production of polymeric microspheres from such highly monodisperse droplet templates. The proposed BMA rule provides new insights into the microflow distribution behaviors in microfluidic ladder networks based on backstepping microflow analysis and provides a rational guideline for the efficient development of microfluidic ladder networks with uniform flow distribution for mass production of highly monodisperse droplets. Moreover, the BMA method provides a general analysis strategy for microfluidic networks with parallel multiple microchannels for rational scale-up.

Transcriptome sequencing analysis of the role of miR-499-5p and SOX6 in chicken skeletal myofiber specification.

MicroRNAs (miRNAs) might play critical roles in skeletal myofiber specification. In a previous study, we found that chicken miR-499-5p is specifically expressed in slow-twitch muscle and that its potential target gene is SOX6. In this study, we performed RNA sequencing to investigate the effects of SOX6 and miR-499-5p on the modulation and regulation of chicken muscle fiber type and its regulatory mechanism. The expression levels of miR-499-5p and SOX6 demonstrated opposing trends in different skeletal muscles and were associated with muscle fiber type composition. Differential expression analysis revealed that miR-499-5p overexpression led to significant changes in the expression of 297 genes in chicken primary myoblasts (CPMs). Myofiber type-related genes, including MYH7B and CSRP3, showed expression patterns similar to those in slow-twitch muscle. According to functional enrichment analysis, differentially expressed genes were mostly associated with muscle development and muscle fiber-related processes. SOX6 was identified as the target gene of miR-499-5p in CPM using target gene mining and luciferase reporter assays. SOX6 knockdown resulted in upregulation of the slow myosin genes and downregulation of fast myosin genes. Furthermore, protein-protein interaction network analysis revealed that MYH7B and RUNX2 may be the direct targets of SOX6. These results indicated that chicken miR-499-5p may promote slow-twitch muscle fiber formation by repressing SOX6 expression. Our study provides a dataset that can be used as a reference for animal meat quality and human muscle disease studies.

Dual-functional polyetheretherketone surface with programmed sequential drug release coating.

The poor bacteriostasis and osseointegration properties of bioinert polyetheretherketone (PEEK) hinder its clinical application. This work reports a simple and versatile strategy for fabricating dual-functional coating with programmed sequential drug release properties on porous PEEK surfaces. The dual-drug-loaded composite coating composed of drug-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles and drug-loaded polyvinyl alcohol (PVA) gel can be immobilized on the surface of sulfonated PEEK by a cyclic freeze-thaw method. Based on the swelling of PVA and the slow degradation of PLGA, the composite coating can realize rapid release of antibacterial drugs and sustained release of osteogenic drugs. The in vitro antibacterial evaluations show that the porous PEEK modified with drug-loaded composite gel coating exhibits an early effective fight against Staphylococcus aureus (S.aureus). The results of in vitro cell experiments show that the PEEK materials modified by the composite gel coating can well support the normal growth, adhesion and proliferation of cells. In addition, the PEEK material coated with the drug-loaded composite gel is found to have positive effects on the osteogenic differentiation of cells in detections of alkaline phosphatase (ALP) activity of cells and the amount of calcium deposition on the surface of the material. The results demonstrate that the proposed porous PEEK modified with dual-drug-loaded composite gel coating simultaneously exhibits excellent osseointegration and exerts early effective antibacterial activity. This dual-functional PEEK material has great application potential in clinical bone tissue repair.