Search

Abstract Background The optimal treatment method for managing unstable Pauwels III femoral neck fractures remains undetermined. The aim of this study was to compare the biomechanical properties of two types of Femoral Neck Anti-rotation and Support System (FNAS) and a Femoral Neck System (FNS) in unstable Pauwels III femoral neck fractures. Methods Eighteen synthetic femoral models were implanted with one of three fixation devices: FNS, FNAS I, or FNAS II. An unstable Pauwels III (OTA/AO 31-B2.3) femoral neck fracture was simulated using a custom-made needle and osteotomy guide. Torsion and axial compression loading tests were conducted, and the torque, torsion angle, load to failure, displacement, and stiffness values were recorded. Results FNAS II exhibited significantly higher torsional stiffness (0.67 ± 0.10 Nm/°) compared to FNAS I (0.52 ± 0.07 Nm/°, P = 0.01) and FNS (0.54 ± 0.07 Nm/°, P = 0.005). FNS demonstrated significantly greater mean axial stiffness (239.24 ± 11.38 N/mm) than both FNAS I (179.33 ± 31.11 N/mm, P = 0.005) and FNAS II (190.07 ± 34.11 N/mm, P = 0.022). FNAS I (302.37 ± 33.88 N/mm, P = 0.001) and FNAS II (319.59 ± 50.10 N/mm, P

Abstract Background Imbalance in energy regulation is a major cause of insulin resistance and diabetes. Melanocortin-4 receptor (MC4R) signaling at specific sites in the central nervous system has synergistic but non-overlapping functions. However, the mechanism by which MC4R in the arcuate nucleus (ARC) region regulates energy balance and insulin resistance remains unclear. Methods The MC4Rflox/flox mice with proopiomelanocortin (POMC) -Cre mice were crossed to generate the POMC-MC4Rflox/+ mice. Then POMC-MC4Rflox/+ mice were further mated with MC4Rflox/flox mice to generate the POMC-MC4Rflox/flox mice in which MC4R is selectively deleted in POMC neurons. Bilateral injections of 200 nl of AAV-sh-Kir2.1 (AAV-sh-NC was used as control) were made into the ARC of the hypothalamus. Oxygen consumption, carbon dioxide production, respiratory exchange ratio and energy expenditure were measured by using the CLAMS; Total, visceral and subcutaneous fat was analyzed using micro-CT. Co-immunoprecipitation assays (Co-IP) were used to analyze the interaction between MC4R and Kir2.1 in GT1-7 cells. Results POMC neuron-specific ablation of MC4R in the ARC region promoted food intake, impaired energy expenditure, leading to increased weight gain and impaired systemic glucose homeostasis. Additionally, MC4R ablation reduced the activation of POMC neuron, and is not tissue-specific for peripheral regulation, suggesting the importance of its central regulation. Mechanistically, sequencing analysis and Co-IP assay demonstrated a direct interaction of MC4R with Kir2.1. Knockdown of Kir2.1 in POMC neuron-specific ablation of MC4R restored the effect of MC4R ablation on energy expenditure and systemic glucose homeostasis, indicating by reduced body weight and ameliorated insulin resistance. Conclusion Hypothalamic POMC neuron-specific knockout of MC4R affects energy balance and insulin sensitivity by regulating Kir2.1. Kir2.1 represents a new target and pathway that could be targeted in obesity.

AbstractCOPD is an inflammatory lung disease that limits airflow and remodels the pulmonary vascular system. This study delves into the therapeutic potential and mechanistic underpinnings of Panax notoginseng Saponins (PNS) in alleviating inflammation and pulmonary vascular remodeling in a COPD rat model. Symmap and ETCM databases provided Panax notoginseng-related target genes, and the CTD and DisGeNET databases provided COPD-related genes. Intersection genes were subjected to protein-protein interaction analysis and pathway enrichment to identify downstream pathways. A COPD rat model was established, with groups receiving varying doses of PNS and a Roxithromycin control. The pathological changes in lung tissue and vasculature were examined using histological staining, while molecular alterations were explored through ELISA, RT-PCR, and Western blot. Network pharmacology research suggested PNS may affect the TLR4/NF-κB pathway linked to COPD development. The study revealed that, in contrast to the control group, the COPD model exhibited a significant increase in inflammatory markers and pathway components such as TLR4, NF-κB, HIF-1α, VEGF, ICAM-1, SELE mRNA, and serum TNF-α, IL-8, and IL-1β. Treatment with PNS notably decreased these markers and mitigated inflammation around the bronchi and vessels. Taken together, the study underscores the potential of PNS in reducing lung inflammation and vascular remodeling in COPD rats, primarily via modulation of the TLR4/NF-κB/HIF-1α/VEGF pathway. This research offers valuable insights for developing new therapeutic strategies for managing and preventing COPD.

BackgroundSishen Pill (SSP) has good efficacy in diarrhea with deficiency kidney-yang syndrome (DKYS), but the mechanism of efficacy involving intestinal microecology has not been elucidated.ObjectiveThis study investigated the mechanism of SSP in regulating intestinal microecology in diarrhea with DKYS.MethodsAdenine combined with Folium sennae was used to construct a mouse model of diarrhea with DKYS and administered with SSP. The behavioral changes and characteristics of gut content microbiota and short-chain fatty acids (SCFAs) of mice were analyzed to explore the potential association between the characteristic bacteria, SCFAs, intestinal inflammatory and kidney function-related indicators.ResultsAfter SSP intervention, the body weight and anal temperature of diarrhea with DKYS gradually recovered and approached the normal level. Lactobacillus johnsonii was significantly enriched, and propionic, butyric, isobutyric and isovaleric acids were elevated. Serum creatinine (Cr), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) levels of the mice were reduced, while serum blood urea nitrogen (BUN) and secretory immunoglobulin A (sIgA) in the colonic tissues were increased. Moreover, there were correlations between L. johnsonii, SCFAs, intestinal inflammatory, and kidney function.ConclusionSSP might suppress the intestinal inflammation by regulating the “L. johnsonii-propionic acid” pathway, thus achieving the effect of treating diarrhea with DKYS.

To investigate the effects of Pseudomonas monteilii SX001 on various parameters of cucumber plants under salt stress, the salt-sensitive cucumber variety “Jinyou No. 4” was used as the test material, and coconut bran was used to simulate salt stress by applying NaCl solution. The results indicated that salt stress significantly reduced the morphological structure, relative growth rate, root morphology, and photosynthetic parameters of the cucumber plants. Leaf starch, soluble sugar, and sucrose contents significantly increased, whereas their levels in roots decreased. Cell membrane damage leads to the accumulation of reactive oxygen species and malondialdehyde, with notable increases in the activities of major antioxidant enzymes such as SOD, CAT, and POD. Nitrogen metabolism was disrupted, as evidenced by a significant decrease in nitrate nitrogen content and an increase in ammonium nitrogen content, as well as a significant reduction in the activity of NR enzymes involved in nitrogen metabolism. The enzyme activity in the cucumber rhizosphere soil decreased. However, Pseudomonas monteilii SX001 significantly enhanced the growth of cucumber seedlings under salt stress, improved photosynthetic efficiency, and facilitated sugar transformation and transport via glucose metabolism. Additionally, Pseudomonas monteilii SX001 reduced the reactive oxygen content and increased antioxidant enzyme activity. It also increased the activity of substrate enzymes and decreased the diversity of rhizosphere soil microorganisms but also increased the abundance of Asticcacaulis, Acinetobacter, Brevundimonas, Pseudomonas, and Enterobacter. These findings demonstrate that Pseudomonas monteilii SX001 is a promising bioinoculant for alleviating salt stress in cucumber production and improving soil health.

Abstract Background To investigate the correlation between computed tomography (CT) radiomic characteristics and key genes for cervical lymph node metastasis (LNM) in oral squamous cell carcinoma (OSCC). Methods The region of interest was annotated at the edge of the primary tumor on enhanced CT images from 140 patients with OSCC and obtained radiomic features. Ribonucleic acid (RNA) sequencing was performed on pathological sections from 20 patients. the DESeq software package was used to compare differential gene expression between groups. Weighted gene co‐expression network analysis was used to construct co‐expressed gene modules, and the KEGG and GO databases were used for pathway enrichment analysis of key gene modules. Finally, Pearson correlation coefficients were calculated between key genes of enriched pathways and radiomic features. Results Four hundred and eighty radiomic features were extracted from enhanced CT images of 140 patients; seven of these correlated significantly with cervical LNM in OSCC (p

Abstract Objective It was reported fatigue or a high-fat diet triggers diarrhea, and intestinal microbiota may play central roles in diarrhea. Therefore, we investigated the association between the intestinal mucosal microbiota and the intestinal mucosal barrier from fatigue combined with a high-fat diet. Method This study divided the Specific pathogen-free (SPF) male mice into the normal group (MCN) and the standing united lard group (MSLD). The MSLD group stood on water environment platform box for 4 h/day for 14 days, and 0.4 mL lard was gavaged from day 8, twice daily for 7 days. Result After 14 days, Mice in the MSLD group showed diarrhea symptoms. The pathological analysis showed structural damage to the small intestine in the MSLD group, with an increasing trend of interleukin-6 (IL-6) and IL-17, and inflammation accompanied by structural damage to the intestine. Fatigue combined with a high-fat diet considerably decreased Limosilactobacillus vaginalis and Limosilactobacillus reuteri, and among them, Limosilactobacillus reuteri positively associated with Muc2 and negatively with IL-6. Conclusion The interactions between Limosilactobacillus reuteri and intestinal inflammation might be involved in the process of intestinal mucosal barrier impairment in fatigue combined with high-fat diet-induced diarrhea.

This study explored the effects of different doses of adenine intake on mice in terms of kidney function, oxidative stress and gut content microbiota to elucidate interactions between adenine-induced kidney function impairment and gut content microbiota disorder. Mice were gavaged with low-dosage adenine suspension (NML), middle-dosage adenine suspension (NMM), high-dosage adenine suspension (NMH) and sterile water (NC). Behaviour, kidney structure and function, colonic structure, oxidative stress and gut content microbiota were detected. Mice in NML, NMM, and NMH groups had significantly lower body weight, anal temperature and food intake, increased water intake, the mice had loose and deformed feces with obvious water stains through the paper. NMM mice presented significantly structural damage to kidney and colonic tissues, considerably higher BUN and Cr, MDA and lower SOD. MDA and SOD levels in NMM and NMH groups were closely associated with Cr and BUN. Moreover, different doses of adenine intake effected the mice gut content microbiota, and enriched the different characteristic bacteria. Characteristic bacteria Lactobacillus and Bifidobacterium presented significant correlations with MDA. Eventually, Lactobacillus and Bifidobacterium mediated oxidative stress pathway involved in the process of adenine-induced kidney injure in mice.

(1) Background: Low-calcium stress can have adverse effects on the rhizosphere environment of cucumber, subsequently impacting cucumber growth. However, plant-growth-promoting rhizobacteria can directly or indirectly enhance plant growth and induce plant tolerance, thereby mitigating the detrimental effects of low-calcium stress on cucumber growth. This study aims to elucidate the role of Bacillus amyloliquefaciens QST713 in the rhizosphere environment of cucumber under low-calcium stress, providing a theoretical basis for the application and promotion of Bacillus amyloliquefaciens. (2) Methods: This study used the ‘JinYou NO.4′ cucumber variety as test material, setting four treatments of CK, CK+Q, LCa, LCa+Q. We conducted measurements of plant height and stem diameter for four groups of cucumber plants: before treatment (0 d), and at 10 d, 20 d, 30 d, and 60 d after treatment. Additionally, we determined the biomass of cucumber plants under different treatments during the peak fruiting period. Inter-root matrix samples of cucumber were collected during the fruiting late period, and the physical and chemical properties and nutrient contents of the inter-root matrix of cucumber were determined, and bacterial microbial diversity and bacterial microbial communities were analysed using Illumina-MiSeq high-throughput sequencing technology. (3) Results: Low-calcium stress significantly inhibits the growth of cucumber plants. However, the application of Bacillus amyloliquefaciens QST713 effectively mitigates the inhibitory effects of low-calcium stress on cucumber growth. The application of Bacillus amyloliquefaciens QST713 was able to improve the physicochemical environment of the matrix and enhanced the absorption and utilisation of matrix nutrients in cucumber. The high-throughput sequencing analysis showed that the richness and diversity of bacterial communities and the number of bacteria decreased significantly under low-calcium stress, and increased significantly after the application of Bacillus amyloliquefaciens QST713. The composition of the dominant bacterial groups of the inter-root matrix of cucumber was basically the same among the four treatments, and the main difference was in the abundance of bacteria. The application of Bacillus amyloliquefaciens QST713 increased the relative abundance of bacteria that decreased under low-calcium stress, and decreased the relative abundance of bacteria that increased under low-calcium stress. (4) Conclusions: The results of this study elucidated the positive effects of Bacillus amyloliquefaciens QST713 on the growth and inter-root environment of cucumber under low-calcium stress, and provided a theoretical basis for in-depth research on the resistance of Bacillus amyloliquefaciens and its popularised application.

The performance of silicone rubber gel elastomers is affected by the composition and structure of the crosslinker. In this work, a two-component addition liquid silicone rubber gel material was developed, and the effects of the contents of two methyl hydro-silicone oils on the compression modulus and breakdown strength of the silicone rubber gel insulating material, as well as the performance change after hot air aging at different times (24 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 h), were studied. The results showed that the breakdown strength and compression modulus exhibited an upward trend with the increase in the hydrogen silicone oil content. The best performance was achieved in the silicone rubber gel with Si-H:Si-Vi = 1.4:1. Moreover, with the increase in aging time, the breakdown strength decreased and the compression modulus increased.

This study aims to investigate the effect of Sishen Pill on the characteristics of gut mucosal microbiota in diarrhea mice with deficiency kidney-yang syndrome. Fifteen Kunming male mice were randomly divided into Normal control group (C), Model self-healing group (X) and Sishen Pill group (S), with 5 mice/cages. Hematoxylin eosin (HE) staining was used to observe the kidney structure. Serum Na+-K+-ATP-ase and Ca2+-Mg2+-ATP-ase were detected by enzyme-linked immunosorbent assay (ELISA), Analysis of intestinal mucosal flora using third-generation high-throughput sequencing. The relative abundance results in the three groups revealed that the dominant bacterial genera: Lactobacillus, Muribaculum and Candidatus-Arthromitus; bacterial species: Lactobacillus johnsonii, Lactobacillus reuteri, Lactobacillus murinus, and Lactobacillus intestinalis, and differences in the presence of major microbiota between the X and S groups. A positive correlation between Lactobacillus johnsonii and both Ca2+-Mg2+-ATP-ase and Na+-K+-ATP-ase was found via correlation analysis. Sishen Pill also changed the manufacture of other secondary metabolites, as well as the metabolism of carbohydrates, glycans, energy, lipids, and other amino acids, and xenobiotics biodegradation and metabolism. In conclusion, Sishen Pill improved kidney structure, energy metabolism and the diversity and structure of intestinal mucosal flora. In addition, Lactobacillus johnsonii may be a characteristic species of Sishen Pill in treating diarrhea with kidney-yang deficiency syndrome.

Abstract In chronic kidney disease, ferric citrate has been shown to be an effective phosphate binder and source of enteral iron; however, the effects of ferric citrate on the kidney have been less well-studied. Here, in Col4α3 knockout mice—a murine model of progressive chronic kidney disease, we evaluated the effects of five weeks of 1% ferric citrate dietary supplementation. As expected, ferric citrate lowered serum phosphate concentrations and increased serum iron levels in the Col4α3 knockout mice. Consistent with decreased enteral phosphate absorption and possibly improved iron status, ferric citrate greatly reduced circulating fibroblast growth factor 23 levels. Interestingly, ferric citrate also lessened systemic inflammation, improved kidney function, reduced albuminuria, and decreased kidney inflammation and fibrosis, suggesting renoprotective effects of ferric citrate in the setting of chronic kidney disease. The factors mediating possible ferric citrate renoprotection, the mechanisms by which they may act, and whether ferric citrate affects chronic kidney disease progression in humans deserves further study.

Extracellular vesicles (EVs), important components of paracrine secretion, are involved in various pathological and physiological processes of the body. In this study, we researched the benefits of EVs secreted by human gingival mesenchymal stem cells (hGMSC-derived EVs) in promoting bone regeneration, thereby providing new ideas for EVs-based bone regeneration therapy. Here, we successfully demonstrated that hGMSC-derived EVs could enhance the osteogenic ability of rat bone marrow mesenchymal stem cells and the angiogenic capability of human umbilical vein endothelial cells. Then, femoral defect rat models were created and treated with phosphate-buffered saline, nanohydroxyapatite/collagen (nHAC), a grouping of nHAC/hGMSCs, and a grouping of nHAC/EVs. The results of our study indicated that the combination of hGMSC-derived EVs and nHAC materials could significantly promote new bone formation and neovascularization with a similar effect to that of the nHAC/hGMSCs group. Our outcomes provide new messages on the role of hGMSC-derived EVs in tissue engineering, which exhibit great potential in bone regeneration treatment.

BackgroundEnvironment, diet, and emotion may trigger diarrhea, but the mechanism is unclear. Dietary habits or environmental factors affect the composition of gut microbiota. This study aimed to investigate the effects of improper diet combined with high humidity and temperature (HTH) environment on the intestinal mucosal microbiota.Materials and methodsKunming mice were randomly assigned to two equal groups of five mice, namely the control (ccm) group and the model (cmm) group. Diarrhea mice with dampness-heat (DSH) were established by improper diet combined with HTH environments. We used 16S rRNA gene amplicon sequencing to analyze the characteristics of intestinal mucosal microbiota and the interaction relationship of function.ResultsOur study shows that the intestinal mucosal microbiota of mice changed significantly after an improper diet combined with the HTH environments. The abundance of Fusobacteria and Haemophilus increased dramatically in the cmm group compared to the ccm group (P

Magnesium (Mg) and its alloys have attracted attention as potential biodegradable materials in orthopedics due to their mechanical and physical properties, which are compatible with those of human bone. However, the effect of the mismatch between the rapid material degradation and fracture healing caused by the adverse effect of hydrogen (H2), which is generated during degradation, on surrounding bone tissue has severely restricted the application of Mg and its alloys. Thus, the development of new Mg alloys to achieve ideal degradation rates, H2 evolution and mechanical properties is necessary. Herein, a novel Mg–1Zn–1Sn-xSr (x = 0, 0.2, 0.4, and 0.6 wt%) quaternary alloy was developed, and the microstructure, mechanical properties, corrosion behavior and biocompatibility in vitro/vivo were investigated. The results demonstrated that a minor amount of strontium (Sr) (0.2 wt %) enhanced the corrosion resistance and mechanical properties of Mg–1Zn–1Sn alloy through grain refinement and second phase strengthening. Simultaneously, due to the high hydrogen overpotential of tin (Sn), the H2 release of the alloys was significantly reduced. Furthermore, Sr-containing Mg–1Zn–1Sn-based alloys significantly enhanced the viability, adhesion and spreading of MC3T3-E1 cells in vitro due to their unique biological activity and the ability to spontaneously form a network structure layer with micro/nanotopography. A low corrosion rate and improved biocompatibility were also maintained in a rat subcutaneous implantation model. However, excessive Sr (>0.2 wt %) led to a microgalvanic reaction and accelerated corrosion and H2 evolution. Considering the corrosion resistance, H2 evolution, mechanical properties and biocompatibility in vitro and in vivo, Mg–1Zn–1Sn-0.2Sr alloy has tremendous potential for clinical applications.

Based on the analysis of earthquakes with M≥5 in Huayingshan fault zone and the present moderate and small seismicity, the background and regional seismicity characteristics in this area are discussed. It is considered that the southern section of the fault zone is the main seismicity area, especially in Yibin, followed by the middle and northern sections. The distribution characteristics of “quiet-active” period of earthquakes with M≥5, the law of “weak activity-enhancement” of earthquakes with M≥3, and the acceleration of strain energy release rate after Changning MS6.0 earthquake in 2019 provide references for the prediction of earthquakes with M≥5 in this area.

In recent years, sweeteners have gained massive popularity under the trend of limiting sugar intake. Our previous study found that Qiweibaizhu Powder (QWBZP) could improve gut microbiota dysbiosis and has good efficacy in treating antibiotic-associated diarrhea (AAD). In this study, we investigated the effects of sucrose, sorbitol, xylitol, and saccharin on the intestinal mucosal microbiota of AAD mice treated with QWBZP. When the AAD model was constructed by being gavaged mixed antibiotic solution, Kunming mice were randomly assigned to seven groups: the control (mn) group, the ADD (mm) group, the QWBZP (mq) group, the saccharin + QWBZP (mc) group, the sucrose + QWBZP (ms) group, the xylito + QWBZP (mx) group, and the sorbitol + QWBZP (msl) group. Subsequently, 16S rRNA gene amplicon sequencing was used to analyze the intestinal mucosal microbiota composition and abundance. The results showed that feces from AAD mice were diluted and wet and improved diarrhea symptoms with QWBZP and sorbitol. In contrast, the addition of sucrose, saccharin, and xylitol delayed the healing of diarrhea. The relative abundance of intestinal mucosal microbiota showed Glutamicibacter, Robinsoniella, and Blautia were characteristic bacteria of the mx group, Candidatus Arthromitus, and Bacteroidales_S24-7_group as the typical bacteria of the mn group, Clostridium_innocuum_group as the distinct bacteria of the mm group. Mycoplasma and Bifidobacterium as the characteristic bacteria of the ms group. Correlation analysis of typical bacterial genera with metabolic functions shows that Blautia negatively correlates with D-Glutamine and D-glutamate metabolism. Bacteroidales_S24-7_group has a significant negative correlation with the Synthesis and degradation of ketone bodies. The study confirmed that sucrose, sorbitol, xylitol, and saccharin might further influence metabolic function by altering the intestinal mucosal microbiota. Compared to the other sweetener, adding sorbitol to QWBZP was the best therapeutic effect for AAD and increased the biosynthesis and degradation activities. It provides the experimental basis for applying artificial sweeteners in traditional Chinese medicine (TCM) as a reference for further rational development and safe use of artificial sweeteners.

A growing body of evidence suggests that the disturbance of intestinal microbiota induced by high-fat diet is the main factor causing many diseases. Dendrobium officinale (DO), a medicinal and edible homologous Chinese herbal medicine, plays essential role in regulating intestinal microbiota. However, the extent of DO on the intestinal contents microbiota in mice fed with a high-fat diet still remains unclear. Therefore, this study explored the role of intestinal contents microbiota in the regulation of adverse effects caused by high-fat diet by DO from the perspective of intestinal microecology. Twenty-four mice were randomly distributed into the normal saline-treated basal diet (bcn), normal saline-treated high-fat diet (bmn), 2.37 g kg−1 days−1 DO traditional decoction-treated high-fat diet (bdn) and 1.19 g kg−1 days−1 lipid-lowering decoction-treated high-fat diet (bjn) groups for 40 days. Subsequently, we assessed the changes in body weight, serum total cholesterol (TC), total triacylglycerol (TG), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C) levels, and the characteristics of intestinal contents microbiota. Results demonstrated that DO exerted the modulating effect on the changes in body weight, TG, TC, LDL-C, and HDL-C levels. Besides, DO decreased the richness and diversity of intestinal contents microbiota, and altered the structure as a whole. Dominant bacteria, Ruminococcus and Oscillospira, varied significantly and statistically. Moreover, DO influenced the carbohydrate, amino acid, and energy metabolic functions. Furthermore, Ruminococcus and Oscillospira presented varying degrees of inhibition/promotion of TG, TC, LDL-C, and HDL-C. Consequently, we hypothesized that Ruminococcus and Oscillospira, as dominant bacteria, played key roles in the treatment of diseases associated with a high-fat diet DO.

ObjectiveThe etiology of apical diseases is diverse, and most are due to incomplete root canal therapy. The common clinical manifestations include gingival abscess, fistula and bone destruction. The currently existing limitation of procedures is that surgeons cannot visually evaluate the surgical areas. We sought to combine mixed reality (MR) technology with a 3-dimensional (3D) printed surgical template to achieve visualization in apical surgery. Notably, no reports have described this application.MethodsWe created visual 3D (V3D) files and transferred them into the HoloLens system. We explained the surgical therapy plan to the patient using a mixed reality head-mounted display (MR-HMD). Then, the 3D information was preliminarily matched with the operative area, and the optimal surgical approach was determined by combining this information with 3D surgical guide plate technology.ResultsWe successfully developed a suitable surgical workflow and confirmed the optimal surgical approach from the buccal side. We completely exposed the apical lesion and removed the inflammatory granulation tissue.ConclusionWe are the first group to use the MR technique in apical surgery. We integrated the MR technique with a 3D surgical template to successfully accomplish the surgery. Desirable outcomes using minimally invasive therapy could be achieved with the MR technique.

Chronic obstructive pulmonary disease (COPD) is one of the most common pulmonary diseases. Evidence suggests that dysbiosis of pulmonary microbiota leads to the COPD pathological process. Yifei Sanjie Formula (YS) is widely used to treat diseases in respiratory systems, yet little is known about its mechanisms. In the present study, we first established the fingerprint of YS as the background for UHPLC-QTOF-MS. Components were detected, including alkaloids, amino acid derivatives, phenylpropanoids, flavonoids, terpenoids, organic acids, phenols, and the like. The therapeutic effect of YS on COPD was evaluated, and the pulmonary function and ventilatory dysfunction (EF50, TV, and MV) were improved after the administration of YS. Further, the influx of lymphocytes was inhibited in pulmonary parenchyma, accompanied by down-regulation of inflammation cytokines via the NLRP3/caspase-1/IL-1β signaling pathway. The severity of pulmonary pathological damage was reversed. Disturbed pulmonary microbiota was discovered to involve an increased relative abundance of Ralstonia and Mycoplasma and a decreased relative abundance of Lactobacillus and Bacteroides in COPD animals. However, the subversive effect was shown. The abundance and diversity of pulmonary microflora were remodeled, especially increasing beneficial genua Lactobacillus and Bacteroides, as well as downregulating pathogenic genua Ralstonia and Mycoplasma in the YS group. Environmental factor correlation analysis showed that growing pulmonary microbiota was positively correlated with the inflammatory factor, referring to Ralstonia and Mycoplasma, as well as negatively correlated with the inflammatory factor, referring to Lactobacillus and Bacteroides. These results suggest that the effects of YS involved remodeling lung microbes and anti-inflammatory signal pathways, revealing that intervention microbiota and an anti-inflammatory may be a potential therapeutic strategy for COPD.

Abstract Background Faster, easier, more economical and more effective versions of the minimally invasive reduction procedure for femoral shaft fractures need to be developed for use by orthopaedic surgeons. In this study, a fracture table was used to restore limb length, and long, curved haemostatic forceps and the lever principle were utilized to achieve minimally invasive reduction and intramedullary nail fixation of femoral shaft fractures. Methods A retrospective analysis involving 20 patients with femoral shaft fractures reduced with a fracture table; long, curved haemostatic forceps; and the lever principle was conducted. The operative effect was evaluated on the basis of the operative time, reduction time, fluoroscopy time, and intraoperative blood loss. Results All 20 cases were reduced in a closed fashion, and no conversions to open reduction were needed. The average operative time and fracture reduction time for all patients were 69.1 ± 13.5 min (range, 50–100 min) and 6.7 ± 1.9 min (range, 3–10 min), respectively. The fluoroscopy exposure time during the reduction process was 5–15 s, with an average time of 8.7 ± 2.7 s. The average intraoperative blood loss was 73.5 ± 22.5 mL (range, 50–150 mL). The patients exhibited excellent alignment in the injured limb after intramedullary nailing. Seventeen patients successfully completed a follow-up after fracture healing. The healing time ranged from 4 to 6 months. Conclusions Displaced femoral shaft fractures in adults can be treated by a labour-saving lever technique involving fragments, 2 haemostatic forceps and soft tissue envelope-assisted closed reduction and intramedullary nail fixation. This technique is easy to perform; reduces blood loss, the fluoroscopy time and the surgical time for intraoperative reduction; and leads to excellent fracture healing.

Silicone rubber (SIR) has been widely used in electrical insulation fields, and the introduction of new materials is very important for the performance improvement of SIR composites. In this work, four different fillers, including aluminium hydroxide (ATH), yimonite (YMT), boron nitride (BN) and mica-filled SIR composites were prepared, and the vulcanization behavior, mechanical properties, insulation performance and hydrophobicity of the SIR composites were investigated and compared. Both BN- and mica-filled SIR composites showed excellent insulation performance, while the ATH-filled SIR composite exhibited the best mechanical properties with an elongation at break of 230% and a tensile strength of 2.9 MPa. The SIR/BN composite showed a breakdown strength of 29.2 kV/mm with a 5% failure rate. The addition of YMT deteriorated the insulation performance of SIR but improved the elongation at break and hydrophobicity, with an elongation at break increasing from 115% to 410% and the static contact angle improving from 109.8° to 115.6°.

Abstract The video request service of users in 5G network will explode, and adaptive bit rate technology can provide users with reliable video response. Placing video resources on edge servers close to users can overcome the problem of excessive network load similar to traditional centralized cloud platform solutions. Moreover, multiple edge servers can provide caching and transcoding support by collaboration mechanisms, which further improves users’ Quality of Experience (QoE). However, the design difficulty of video caching and content distribution strategies is increased due to the diversity of collaboration mechanisms and the competition between local and collaborative services of edge servers for computing and storage resources. In order to solve this problem, video cache and content distribution problem is modeled as random integer programming problem in the multi-edge server at most two-hop collaboration scenario. In order to improve the security of video data transmission, the video stream is encrypted using an encryption algorithm based on Logistic chaotic-Quantum-dot Cellular Automata (QCA). For improving the efficiency of solving integer programming problems, this paper uses a pyramid intelligent evolution algorithm based on optimal cooperation strategy to solve this problem. Simulation experiments show that our proposed method can obtain higher QoE value compared with several newer methods. In addition, the average access delay of proposed method is shortened by more than 27.98%, which verifies its reliability.

To meet the growing demand for antibacterial implants for bone-implant-associated infection therapy and avoid the adverse effects of secondary surgery, a degradable platform with pH responsiveness and ion-associated antibacterial properties was constructed. A small amount of Sn added to Mg-1Zn alloy reduces the biocorrosion rate, which can be attributed to Sn participation in outer-layer film formation, significantly reducing the biocorrosion rate and hydrogen evolution rate after implantation in vivo. These Mg alloys, which are susceptible to degradation in the acidic bacterial microenvironment, degrade by releasing Mg, Zn and Sn, producing favorably alkaline and antibacterial conditions. Samples with the composition of Mg-1Zn-0.5Sn were found to be beneficial for promoting initial cell adhesion and proliferation, resulting in improved biocompatibility and biosafety. The biocompatibility of this alloy was confirmed by the healthy behavior of animals and the absence of acute or chronic toxicity in the liver, spleen, and kidneys. Our results demonstrate that Mg-1Zn-0.5Sn is safe for biological systems, enabling its efficacious use in biomedical applications.

Abstract The utilization of mixed cations is beneficial for taking the advantages of cations and achieving highly efficient perovskite solar cells (PSCs). Herein, the precisely small incorporation of CH(NH2)2 (FA) cations in methyl ammonium lead iodide (MAPbI3) enables the formation of compact, smooth perovskite film with high crystallinity. Consequently, the short-circuit current and the fill factor of the PSCs based on FA x MA1-x PbI3 perovskite are greatly improved, leading to the enhanced device efficiency. The champion PSC based on FA0.1MA0.9PbI3 exhibits a remarkably high efficiency of 22.02%. Furthermore, the PSCs based on FA0.1MA0.9PbI3 perovskite also show improved device stability. This work provides a simple approach to fabricate high-quality perovskite films and high-performance PSCs with better stability.

Background: Several clinical trials have recently been conducted to elucidate the effectiveness of photofunctionalization. The aim of this review was to systematically analyze the clinical effects of photofunctionalization on implant stability and marginal bone loss (MBL). Methods: An electronic search in four databases and a manual search were conducted in September 2022. Randomized controlled trials (RCTs), clinical controlled trials (CCTs), and cohort and case-control studies evaluating the effects of photofunctionalization on implant stability or marginal bone loss (MBL) in humans were included. The methodological quality assessment using RoB 2.0 and the ROBINS-I tool was performed based on different study designs. Results: Seven studies were included for a qualitative analysis, and five of them were chosen for a meta-analysis. The meta-analysis revealed that photofunctionalization significantly improved the stability of the implant 2 months after implantation (p = 0.04; MD = 3.48; 95% CI = −0.23 to 6.73) and increased the osseointegration speed index (OSI) (p = 0.007; MD = 2.13; 95% CI = 0.57 to 3.68). However, no significant improvements of implant stability were observed 2 weeks (p = 0.62), 4 weeks (p = 0.31), nor 4 months (p = 0.24) after implantation. The evaluation presented no significant reductions in MBL. Conclusions: Based on the positive effect of photofunctionalization on the rate of establishing implant stability, photofunctionalization may provide an effective and practical strategy to achieve faster osseointegration and reduce the overall healing time. Photofunctionalization appears to improve the implant stability. However, the clinical effect of photofunctionalization on MBL remains unclear due to the shortage of available studies.

Background: Extensive evidence suggests that gut microbiota may interact with the kidneys and play central roles in the pathogenesis of disease. However, the association of gut microbiota-kidneys in diarrhea remains unclear. Methods: A diarrhea mouse model was constructed by combining adenine with Folium sennae. We analyzed the characteristics of the gut content microbiota and short chain fatty acids (SCFAs); and explored the potential link between gut content microbiota, SCFAs, intestinal inflammatory response and kidney function. Results: Characteristic bacteria Lactobacillus intestinalis and Bacteroides acidifaciens were enriched in the gut contents of mice. The productions of SCFAs were remarkably inhibited. Model mice presented an increased trend of creatinine (Cr), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), a decreased trend of blood urea nitrogen (BUN) and secretory immunoglobulin A (SIgA). The pathological analysis proved obvious damage to the kidney structure. Lactobacillus intestinalis and Bacteroides acidifaciens exisited in the correlations with acetic acid, intestinal inflammatory response and kidney function. Conclusions: Adenine combined with Folium sennae-induced diarrhea, altered the structure and function of the gut content microbiota in mice, causing the enrichment of the characteristic bacteria Lactobacillus intestinalis and Bacteroides acidifaciens. The interactions between Lactobacillus intestinalis, Bacteroides acidifaciens and acetic acid, intestinal inflammation, and kidney function might be involved in the process of gut-kidney impairment in adenine, combined with Folium sennae-induced diarrhea.

Oral squamous cell carcinoma (OSCC) is the most common malignant epithelial tumor in the oral cavity. Emerging evidence has demonstrated the important function roles of long noncoding RNAs (lncRNAs) in human cancers. LncRNA promoter of CDKN1A antisense DNA damage activated RNA (PANDAR) functions as an oncogene in multiple carcinomas, whereas its function in OSCC has not been investigated yet. The aim of our study is to investigate the possible regulatory mechanism of PANDAR in OSCC. First of all, PANDAR was highly expressed in OSCC cells and loss-of-function assays mediated by CRISPR-dCas9 observed that PANDAR silencing restrained cell proliferation and promoted cell apoptosis. Then we found and confirmed the interaction between PANDAR and serine and arginine rich splicing factor 7 (SRSF7). Subsequently, serine/threonine-protein kinase pim-1 (PIM1) was proved to be regulated by PANDAR in SRSF7-dependant way. Rescue experiments validated that PANDAR modulated the proliferation and apoptosis in OSCC through PIM1. In conclusion, PANDAR bound with SRSF7 to increase PIM1 expression, hence promoting the development of OSCC. These data shed new lights into the seeking for effective diagnostic biomarkers and therapeutic targets for OSCC patients.

The tumor microenvironment (TME) plays a critical role in the initiation and progression of cancer. However, the specific mechanism of its regulation in head and neck squamous cell carcinoma (HNSCC) remains unclear. In this study, we first applied the ESTIMATE method to calculate the immune and stromal scores in patients’ tumor tissues from The Cancer Genome Atlas (TCGA) database. GSE41613, GSE30784, and GSE37991 data sets from the Gene Expression Omnibus (GEO) database were recruited for further validation. Differentially expressed genes (DEGs) were identified and then analyzed by Cox regression analysis and protein-protein interaction (PPI) network construction. DEGs significantly associated with prognosis and TME will be identified as hub genes. These genes were also validated at the protein level by immunohistochemical analysis of 10 pairs of primary tumor tissues and the adjacent normal tissues from our institution. The relationship between hub genes expression and immune cell fraction estimated by CIBERSORT software was also examined. 275 DEGs were significantly associated with TME. CCR4, CCR8, and P2RY14 have then identified as hub genes by intersection Cox and PPI analysis. Further investigation revealed that the expression of CCR4, CCR8, and P2RY14 was negatively correlated with clinicopathological characteristics (clinical stage, T stage) and positively associated with survival in HNSCC patients, especially in male patients. The expression of CCR8 and P2RY14 was lower in males than in females. CCR8 and P2RY14 were differentially expressed in tumor tissues than normal tissues, and the results were validated at the protein level by immunohistochemistry experiments. Gene set enrichment analysis (GSEA) showed that the high expression groups’ hub genes were mainly enriched for immune-related activities. In the low-expression groups, genes were primarily enriched in metabolic pathways. CIBERSORT results showed that the expression of these genes was all negatively correlated with the fraction of memory B cells and positively correlated with the fraction of the other four cells, including naive B cells, resting T cells CD4 memory, T cells follicular helper, and T cells regulatory (Tregs). The results suggest that CCR4, CCR8, and P2RY14 may be responsible for maintaining the immune dominance of TME, thus leading to a better prognosis.

The mitigation of interfacial charge accumulation in solution-processed organic light-emitting diodes (s-OLEDs) is an effective method to improve device performance. In this study, the polar solvent vapor annealing (PSVA) method was used to treat two layers in s-OLED, PEDOT:PSS and mCP:DMAC-DPS emitting layers, separately, to optimize the carrier transmission and balance. After the double-layer PSVA treatment, the current efficiency increased, the lifetime of the device is improved, the efficiency roll-off alleviated from 33.3% to 26.6%, and the maximum brightness increased by 31.3%. It is worth mentioning that the work function of the EML interface reduced by 0.36 eV, and the initial injection voltage of the electrons also reduced. Simulating the solubility of the LUMO and HOMO molecule parts of the mCP and DMAC-DPS, it was found that the LUMO parts had stronger polarity and higher solubility in polar solution than the HOMO parts. By comparing the untreated luminescent layer films, it was found that the PSVA treatment improved the uniformity of the film morphology. We may infer that a more ordered molecular arrangement enhances carrier transport as the LUMO parts tend to be close to the surface and the reduced local state traps on the EML surface promote electron injection. According to the experimental results, the injection of holes and electrons is enhanced from both sides of the EML, respectively, and the charge accumulated at the interface of s-OLEDs is significantly reduced due to the improvement of carrier-transported characteristics.

Self-assembled peptide scaffolds based on D-RADA16 are an important matrix for controlled drug release and three-dimensional cell culture. In this work, D-RADA16 peptide hydrogels were coated on artificial bone composed of nano-hydroxyapatite/polyamide 66 (nHA/PA66) to obtain a porous drug-releasing structure for treating bone defects. The developed materials were characterized via transmission electron microscopy and scanning electron microscopy. The proliferation and adhesion of bone mesenchymal stem cells (BMSCs) were examined by confocal laser microscopy and CCK-8 experiments. The osteogenic ability of the porous materials towards bone BMSCs was examined in vitro by staining with Alizarin Red S and alkaline phosphatase, and bioactivity was evaluated in vivo. The results revealed that nHA/PA66/D-RADA16/bFGF reduces the degradation rate of D-RADA16 hydrogels and prolongs sustained release of bFGF, which would promote BMSCs proliferation, adhesion and osteogenesis in vitro and bone repair in vivo. Thus, it deserves more attention and is worthy of further research.

Castration-resistant prostate cancer (CRPC) is a progressed stage of prostate cancer, which requires better understanding of the mechanisms and remains an unmet clinical need. As a common oncogene, K-Ras is associated with malignant behavior in different types of tumors but its role in CRPC is unknown. The present study aims to find the mechanism of K-Ras in CRPC and whether it can be used as a crucial molecule for the treatment of CRPC. For this purpose, tissue samples from primary prostate cancer (PPC) and CRPC patients were analyzed by immunohistochemistry and the data showed that K-Ras was elevated in CRPC. More importantly, higher K-Ras expression was related to a shorter recurrence-free survival time in patients with CRPC. In addition, K-Ras promoted the invasion, migration, and drug resistance of CRPC cells by activation of PLCε/PKCε signaling pathway. Meanwhile, the inhibitor of K-RasG12C mutants was able to inhibit malignant behavior of CRPC cells in vitro and in vivo. Inhibitors of K-RasG12C mutants have entered clinical trials. Taken together, the study shows that K-Ras may activate PKCε through PLCε, resulting in the alterations of malignant behavior of CRPC. Inhibitor 9, an inhibitor of the K-RasG12C mutant, has a strong anti-tumor effect in CRPC, which potentially suggests that inhibitors of this nature may serve as a promising treatment for CRPC.

Ferroportin (Fpn) is essential for mammalian iron homeostasis as it exports iron from cells into blood circulation, but the molecular mechanisms of Fpn-mediated iron transport remain obscure. Here the authors use biophysical approaches to reveal that Ca2+ is a required cofactor for Fpn transport activity.

Although reported ternary polymer solar cells have higher power conversion efficiency than binary polymers, the mechanism of exciton separation and charge transport in this complex ternary system is still unclear. Herein, based on PM6:Y6:ITIC-M ternary solar cells, we combine the technique of luminescence spectroscopy, including electroluminescence (EL) and photoluminescence (PL) with photovoltaic measurements, to understand clearly the detailed roles of ITIC-M as the third component in the contribution of device performance. The results show that ITIC-M can form the alloy-like composite with Y6 but leave individual Y6 acceptor to conduct charge transfer with PM6 donor, which improves Voc but decreases Jsc because of poor charge transfer capacity of ITIC-M. Meanwhile, the energy transfer from PM6 to ITIC-M exists in the active layers; small IE suppresses exciton dissociation. Deteriorating performance of solar cells demonstrates that, except for complementary absorption spectrum and suitable energy levels in PM6:Y6:ITIC-M system, the synergetic effects of carrier dynamics among different organic materials play an important role in influencing the performance of ternary solar cells.

Background/aimPatients with polycystic ovary syndrome (PCOS), characterized by anovulation, hyperandrogenemia and polycystic ovaries, are still vulnerable to undergo recurrent pregnancy loss and premature labor even though the ovulatory process is pharmacologically recovered. However, its potential mechanism remains unknown. Thus, our aim was to investigate the effect and mechanism of hyperandrogenemia and flutamide (a non-steroidal anti-androgen) on the embryo implantation and pregnancy during mid-pregnancy.MethodsWe used a mouse model in which PCOS-like hyperandrogenemia was induced by subcutaneous injection of testosterone propionate. In this model, we observed the effect of hyperandrogenemia and flutamide on the decidualization, angiogenesis and uNK cells by methods of immunohistochemistry, quantitative PCR, western blotting and Dolichos biflorus agglutinin (DBA) lectin staining.ResultsTestosterone and flutamide treatment did not significantly influence the numbers of implanted embryo compared with the control group. However, different doses of testosterone significantly increased the ratio of resorbed /implanted embryo, decreased the level of prl8a2 mRNA and cyclin D3 protein, inhibited the uterine angiogenesis and reduced the numbers of uNK cells, but combined treatment with flutamide markedly decreased the resorbed embryos, increased expressions of prl8a2 mRNA and cyclin D3 protein and angiogenesis and numbers of uNK cells.ConclusionFlutamide treatment can efficiently ameliorate the hyperandrogenemia-induced the disorders in aspects of decidualization, angiogenesis and uNK cells, which further improve the poor endometrial receptivity in PCOS patients.

Nowadays, most blue organic light emitting diodes (OLEDs) are fabricated by using sky-blue emitters which are more easily synthesized when compared with other deep blue emitters. Herein, we put forward a new idea of using an optical micro-cavity based on metal electrodes to regulate electroluminance (EL) spectra of sky-blue organic light emitting diodes to obtain a saturated deep blue emission with a narrowed full-width at half-maximum (FWHM). First, we simulate micro-cavity OLEDs and find that the transmission of the anode plays an important role in the forward emission. Meanwhile, the optical path of micro-cavity OLEDs as well as the phase shifting from electrodes influence the EL spectra and induce the extra intensity enhancement. The results show that when the resonant cavity optical path is regulated by changing the thickness of emitting layer (EML) from 25 nm to 75 nm in the micro-cavity, the EL peak of blue OLEDs has a redshift from 479 nm to 493 nm with FWHM shifting from 69.8 nm to 83.2 nm, when compared to the device without the micro-cavity, whose approximate EL peak and FWHM are 487 nm and 87 nm, respectively. However, the efficiency of electroluminescence decreases in micro-cavity OLEDs. We speculate that this is on account of the ohmic contact between ITO and Ag, the surface plasma effect and the rough morphology induced by Ag electrodes.

At present, most high-performance non-fullerene materials are centered on fused rings. With the increase in the number of fused rings, production costs and production difficulties increase. Compared with other non-fullerenes, small molecule INTIC has the advantages of easy synthesis and strong and wide infrared absorption. According to our previous report, the maximum power conversion efficiency (PCE) of an organic solar cell using PTB7-Th:INTIC as the active layer was 7.27%. In this work, other polymers, PTB7, PBDB-T and PBDB-T-2F, as the donor materials, with INTIC as the acceptor, are selected to fabricate cells with the same structure to optimize their photovoltaic performance. The experimental results show that the optimal PCE of PBDB-T:INTIC based organic solar cells is 11.08%, which, thanks to the open voltage (VOC) increases from 0.80 V to 0.84 V, the short circuit current (JSC) increases from 15.32 mA/cm2 to 19.42 mA/cm2 and the fill factor (FF) increases from 60.08% to 67.89%, then a 52.4% improvement in PCE is the result, compared with the devices based on PTB7-Th:INTIC. This is because the PBDB-T:INTIC system has better carrier dissociation and extraction, carrier transportation and higher carrier mobility.

In inverted perovskite solar cells (PSCs), high-quality perovskite film grown on hole-transporting material (HTM) with pinhole-free coverage and a large grain size is crucial for high efficiency. Here, we report on the growth of pinhole-free and large grain CH3NH3PbI3 crystals favored by a hydrophobic small molecular HTM, namely, 4,4′-Bis(4-(di-p-toyl)aminostyryl)biphenyl (TPASBP). The hydrophobic surface induced by TPASBP suppressed the density of the perovskite nuclei and heterogeneous nucleation, thus promoting the perovskite to grow into a dense and homogeneous film with a large grain size. The CH3NH3PbI3 deposited on the TPASBP exhibited better crystallization and a lower trap density than that on the hydrophilic surface of indium tin oxide (ITO), resulting in a significant reduction in carrier recombination. Combined with the efficient hole extraction ability of TPASBP, a high efficiency of 18.72% in the inverted PSCs fabricated on TPASBP was achieved.

Hepcidin, the iron-regulatory hormone and acute phase reactant, is proposed to contribute to the pathogenesis of atherosclerosis by promoting iron accumulation in plaque macrophages, leading to increased oxidative stress and inflammation in the plaque (the “iron hypothesis”). Hepcidin and iron may thus represent modifiable risk factors in atherosclerosis. We measured hepcidin expression in Apoe−/− mice with varying diets and ages. To assess the role of macrophage iron in atherosclerosis, we generated Apoe−/− mice with macrophage-specific iron accumulation by introducing the ferroportin ffe mutation. Macrophage iron loading was also enhanced by intravenous iron injection. Contrary to the iron hypothesis, we found that hepatic hepcidin expression was not increased at any stage of the atherosclerosis progression in Apoe−/− or Apoe/ffe mice and that the atherosclerotic plaque size was not increased in mice with elevated macrophage iron. Our results strongly argue against any significant role of macrophage iron in atherosclerosis progression in mice.

Small molecule organic solar cells (SMOSCs) have attracted extensive attention in recent years. Squaraine (SQ) is a kind of small molecule material for potential use in high-efficiency devices, because of its high extinction coefficient and low-cost synthesis. However, the charge carrier mobility of SQ-based film is much lower than other effective materials, which leads to the pretty low fill factor (FF). In this study, we improve the performance of SQ derivative-based solar cells by incorporating PCDTBT into LQ-51/PC71BM host binary blend film. The incorporation of PCDTBT can not only increase the photon harvesting, but also provide an additional hole transport pathway. Through the charge carrier mobility and transient photovoltage measurement, we find that the hole mobility and charge carrier lifetime increase in the ternary system. Also, we carefully demonstrate that the charge carrier transport follows a parallel-like behavior.

Cerebral small vessel disease (CSVD) is a leading cause of stroke and vascular cognitive impairment and dementia. Studying monogenic CSVD can reveal pathways that are dysregulated in common sporadic forms of the disease and may represent therapeutic targets. Mutations in collagen type IV alpha 1 (COL4A1) and alpha 2 (COL4A2) cause highly penetrant CSVD as part of a multisystem disorder referred to as Gould syndrome. COL4A1 and COL4A2 form heterotrimers [a1α1α2(IV)] that are fundamental constituents of basement membranes. However, their functions are poorly understood and the mechanism(s) by which COL4A1 and COL4A2 mutations cause CSVD are unknown. We used histological, molecular, genetic, pharmacological, and in vivo imaging approaches to characterize central nervous system (CNS) vascular pathologies in Col4a1 mutant mouse models of monogenic CSVD to provide insight into underlying pathogenic mechanisms. We describe developmental CNS angiogenesis abnormalities characterized by impaired retinal vascular outgrowth and patterning, increased numbers of mural cells with abnormal morphologies, altered contractile protein expression in vascular smooth muscle cells (VSMCs) and age-related loss of arteriolar VSMCs in Col4a1 mutant mice. Importantly, we identified elevated TGFβ signaling as a pathogenic consequence of Col4a1 mutations and show that genetically suppressing TGFβ signaling ameliorated CNS vascular pathologies, including partial rescue of retinal vascular patterning defects, prevention of VSMC loss, and significant reduction of intracerebral hemorrhages in Col4a1 mutant mice aged up to 8 months. This study identifies a novel biological role for collagen α1α1α2(IV) as a regulator of TGFβ signaling and demonstrates that elevated TGFβ signaling contributes to CNS vascular pathologies caused by Col4a1 mutations. Our findings suggest that pharmacologically suppressing TGFβ signaling could reduce the severity of CSVD, and potentially other manifestations associated with Gould syndrome and have important translational implications that could extend to idiopathic forms of CSVD.

High efficiency, solution-processed, organic light emitting devices (OLEDs), using a thermally-activated delayed fluorescent (TADF) emitter, 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN), are fabricated, and the transient electroluminescence (EL) decay of the device with a structure of [ITO/PEDOT: PSS/4CzIPN 5 wt % doped 4,40-N,N0-dicarbazolylbiphenyl(CBP)/bis-4,6-(3,5-di-4-pyridylphenyl)-2-methylpyrimidine (B4PyMPM)/lithium fluoride (LiF)/Al], is systematically studied. The results shed light on the dominant operating mechanism in TADF-based OLEDs. Electroluminescence in the host–guest system is mainly produced from the 4CzIPN emitter, rather than the exciplex host materials.

In this study, we prepared nano-hydroxyapatite/polyamide 66/glass fibre (n-HA/PA66/GF) bioactive bone screws. The microstructure, morphology and coating of the screws were characterised, and the adhesion, proliferation and viability of MC3T3-E1 cells on n-HA/PA66/GF scaffolds were determined using scanning electron microscope, CCK-8 assays and cellular immunofluorescence analysis. The results confirmed that n-HA/PA66/GF scaffolds were biocompatible and had no negative effect on MC3T3-E1 cells in vitro. To investigate the in vivo biocompatibility, internal fixation properties and osteogenesis of the bioactive screws, both n-HA/PA66/GF screws and metallic screws were used to repair intercondylar femur fractures in dogs. General photography, CT examination, micro-CT examination, histological staining and biomechanical assays were performed at 4, 8, 12 and 24 weeks after operation. The n-HA/PA66/GF screws exhibited good biocompatibility, high mechanical strength and extensive osteogenesis in the host bone. Moreover, 24 weeks after implantation, the maximum push-out load of the bioactive screws was greater than that of the metallic screws. As shown by their good cytocompatibility, excellent biomechanical strength and fast formation and ingrowth of new bone, n-HA/PA66/GF screws are thus suitable for orthopaedic clinical applications.