Exploring the role of ITGB6: fibrosis, cancer, and other diseases.

Integrin ß6 (ITGB6), a member of the integrin family of proteins, is only present in epithelial tissues and frequently associates with integrin subunit αv to form transmembrane heterodimers named integrin αvß6. Importantly, ITGB6 determines αvß6 expression and availability. In addition to being engaged in organ fibrosis, ITGB6 is also directly linked to the emergence of cancer, periodontitis, and several potential genetic diseases. Therefore, it is of great significance to study the molecular-biological mechanism of ITGB6, which could provide novel insights for future clinical diagnosis and therapy. This review introduces the structure, distribution, and biological function of ITGB6. This review also expounds on ITGB6-related diseases, detailing the known biological effects of ITGB6.

Core-shell magnetic covalent organic polymer nanocomposites as an adsorbent for the extraction of flavonoids.

A novel 3D magnetic nanocomposite material based on covalent organic polymers was successfully synthesized and utilized as an efficient sorbent for magnetic solid-phase extraction. It exhibited a regular core-shell structure, large specific surface area, superior stability, and paramagnetism. To evaluate its extraction efficiency, six flavonoids were tested, demonstrating maximum adsorption capacities ranging from 90 to 218 mg/g. Additionally, the material exhibited remarkable reusability and mechanical stability, maintaining its original state over eight cycles with consistent recovery. An analytical strategy combining magnetic solid-phase extraction with high performance liquid chromatography and tandem mass spectrometry was developed for the determination of flavonoids in orange, honey, soybean, and Dioscorea bulbifera L. samples. The low limits of detection (0.01-0.1 ng/mL) and limits of quantification (0.05-0.5 ng/mL), as well as satisfactory recovery (80.4-114.8%), were obtained. The linear range started from the limits of quantification to 500 ng/mL with R2 ≥ 0.9929. These results suggest that the prepared adsorbent possesses excellent adsorption capabilities for flavonoids, highlighting its significant potential for detecting these compounds in complex sample matrices.

Casein phosphopeptide calcium chelation: preparation optimization, in vitro gastrointestinal simulated digestion, and peptide fragment exploration.

BACKGROUND: Calcium is important in the formation of bones and teeth, cell metabolism, and other physiological activities. In this work, casein phosphopeptide-calcium chelate (CPP-Ca) was synthesized and the optimal process parameters for the chelation reaction were obtained. The bioavailability of calcium in CPP-Ca was investigated by in vitro gastrointestinal simulated digestion. The existence of phytic acid and oxalic acid in the digestion system was evaluated to clarify the calcium holding ability of casein phosphopeptide (CPP). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to identify oligopeptides from CPP-Ca. RESULTS: The optimal process parameters for the chelation reaction were: peptide concentration 7.76 mgmL-1 , pH 8.54, and reaction temperature 43.3 °C. The digestion in vitro results indicated that the calcium release rate of CPP-Ca in the stomach for 2 h reached 85%, and about 50% of the ionized calcium was re-chelated with CPP in the intestine. Phytic acid and oxalic acid could lead to a sharp decrease in soluble calcium but around 50% of the calcium was still retained in the form of chelates in the presence of CPP. The LC-MS/MS identified 19 casein-derived oligopeptides after digestion, and calcium modifications were found on eight peptides derived from ß-casein and αs2 -casein. CONCLUSIONS: This study clarified the excellent calcium holding capacity of CPP in the presence of phytic acid and oxalic acid. Liquid chromatography-tandem mass spectrometry also revealed peptide changes, and identified peptides that chelate with calcium. These findings provided significant insights that could be relevant to the further utilization and product development of peptide-calcium chelate in the food industry. © 2023 Society of Chemical Industry.

Preparation of silk fibroin/hyaluronic acid composite hydrogel based on thiol-ene click chemistry. / 基于巯基-çƒ¯ç‚¹å‡»åŒ–å­¦åˆ¶å¤‡ä¸ç´ è›‹ç™½/é€æ˜Žè´¨é ¸å¤åˆæ°´å‡èƒ¶.

OBJECTIVES: To design and prepare silk fibroin/hyaluronic acid composite hydrogel. METHODS: The thiol modified silk fibroin and the double-bond modified hyaluronic acid were rapidly cured into gels through thiol-ene click polymerization under ultraviolet light condition. The grafting rate of modified silk fibroin and hyaluronic acid was characterized by 1H NMR spectroscopy; the gel point and the internal microstructure of hydrogels were characterized by rheological test and scanning electron microscopy; the mechanical properties were characterized by compression test; the swelling rate and degradation rate were determined by mass method. The hydrogel was co-cultured with the cells, the cytotoxicity was measured by the lactate dehydrogenase method, the cell adhesion was measured by the float count method, and the cell growth and differentiation on the surface of the gel were observed by scanning electron microscope and fluorescence microscope. RESULTS: The functional group substitution degrees of modified silk fibroin and hyaluronic acid were 17.99% and 48.03%, respectively. The prepared silk fibroin/hyaluronic acid composite hydrogel had a gel point of 40-60 s and had a porous structure inside the gel. The compressive strength was as high as 450 kPa and it would not break after ten cycles. The water absorption capacity of the composite hydrogel was 4-10 times of its own weight. Degradation experiments showed that the hydrogel was biodegradable, and the degradation rate reached 28%-42% after 35 d. The cell biology experiments showed that the cytotoxicity of the composite gel was low, the cell adhesion was good, and the growth and differentiation of the cells on the surface of the gel were good. CONCLUSIONS: The photocurable silk fibroin/hyaluronic acid composite hydrogel can form a gel quickly, and has excellent mechanical properties, adjustable swelling rate and degradation degree, good biocompatibility, so it has promising application prospects in biomedicine.

Synchronous Reconstruction of the Jaw Using a "One and a Half"-Barrel Fibular Bone Graft for Ossifying Fibroma Patients.

BACKGROUND: Ossifying fibroma is one of the common benign tumors that affect the appearance and functions of the jaw. Ossifying fibroma may exhibit a wide range of biological behaviors, leading to deformities involving the jaw and other secondary facial deformities. Hence, to improve the function of the jaw and the patient's general facial appearance (bearing in mind each patient's facial shape and, or appearance), the authors thus, however, used a ''one and a half"-barrel fibular bone graft to achieve the ideal height and radian of the bone graft. CASE PRESENTATION: Between July 2017 and January 2021, the authors retrospectively collected and analyzed clinical and surgical data from 39 patients who had undergone operations in our hospital. Twenty patients were operated on using our new surgical method, whereas 19 patients received conventional or debulking operation. Clinical factors associated with the operation were assessed, including classification of the jaw defects, perioperative complications, and postoperative outcomes. RESULTS: All the flaps ultimately survived. According to the postoperative satisfaction survey, patients who underwent reconstruction were satisfied with their postoperative facial appearance, with an average of 8.5 out of 10. Based on the preoperative clinical data, 26 patients had suitable bone grafts for dentures to improve their oral function. CONCLUSIONS: A ''one and a half''-barrel fibular bone graft effectively improves the facial appearance of patients and as well as provides an appropriate height and radian for the bone graft.

Rapid and mass production of biopesticide Trichoderma Brev T069 from cassava peels using newly established solid-state fermentation bioreactor system.

Converting agricultural waste into value-added biopesticides to replace chemical pesticides for plant protection is a good alternative for environmental sustainability and resource recycling. In this study, five tropical wastes (cassava peels, banana pseudostem, coconut shell, sugarcane bagasse, and pineapple peels) were screened as substrates for the rapid production of biopesticide Trichoderma Brev T069. Five single tests and a Box-Behnken design (BBD) with response surface methodology were used to optimize the culture conditions to improve the spore yield. The results showed that cassava peel was the optimal solid fermentation substrate, and the optimization enabled a spore yield of 9.31 × 109 spores/g at 3rd day, which was equal to 93.19% of spore yield obtained at 5th day (9.99 × 109 spores/g). A newly packed-bed bioreactor with agitation and ventilation system was developed and used to expand the production that 250 kg of biopesticide (2.89 × 109 spores/g) could be available on the 3rd day. A pot experiment indicated that the biopesticide T. Brev T069 obtained under this production system, when applied at 1 × 107 spores/g of soil had a 64.65% biocontrol efficiency on banana fusarium wilt. This study provides a practical solution for turning a tropical waste into an effective biopesticide which can prevent banana wilt disease, thereby helping to reduce disease management cost and overcome environmental hazards caused by synthetic pesticides.

In vitro evaluation of nanoplastics using human lung epithelial cells, microarray analysis and co-culture model.

Nanoplastics, including polystyrene nanoplastics (PS-NPs), are widely existed in the atmosphere, which can be directly and continuously inhaled into the human body, posing a serious threat to the respiratory system. Therefore, it is urgent to estimate the potential pulmonary toxicity of airborne NPs and understand its underlying mechanism. In this research, we used two types of human lung epithelial cells (bronchial epithelium transformed with Ad12-SV40 2B, BEAS-2B) and (human pulmonary alveolar epithelial cells, HPAEpiC) to investigate the association between lung injury and PS-NPs. We found PS-NPs could significantly reduce cell viability in a dose-dependent manner and selected 7.5, 15 and 30 µg/cm2 PS-NPs as the exposure dosage levels. Microarray detection revealed that 770 genes in the 7.5 µg/cm2 group and 1951 genes in the 30 µg/cm2 group were distinctly altered compared to the control group. Function analysis suggested that redox imbalance might play central roles in PS-NPs induced lung injury. Further experiments verified that PS-NPs could break redox equilibrium, induce inflammatory effects, and triggered apoptotic pathways to cause cell death. Importantly, we found that PS-NPs could decrease transepithelial electrical resistance by depleting tight junctional proteins. Result also demonstrated that PS-NPs-treated cells increased matrix metallopeptidase 9 and Surfactant protein A levels, suggesting the exposure of PS-NPs might reduce the repair ability of the lung and cause tissue damage. In conclusion, nanoplastics could induce oxidative stress and inflammatory responses, followed by cell death and epithelial barrier destruction, which might result in tissue damage and lung disease after prolonged exposure.

Effect of Side Chain Substituent Volume on Thermoelectric Properties of IDT-Based Conjugated Polymers.

A p-type thermoelectric conjugated polymer based on indacenodithiophene and benzothiadiazole is designed and synthesized by replacing normal aliphatic side chains (P1) with conjugated aromatic benzene substituents (P2). The introduced bulky substituent on P2 is detrimental to form the intensified packing of polymers, therefore, it hinders the efficient transporting of the charge carriers, eventually resulting in a lower conductivity compared to that of the polymers bearing aliphatic side chains (P1). These results reveal that the modification of side chains on conjugated polymers is crucial to rationally designed thermoelectric polymers with high performance.

Correlation of skull morphology and bite force in a bird-eating bat (Ia io; Vespertilionidae).

BACKGROUND: Genetic and ecological factors influence morphology, and morphology is compatible with function. The morphology and bite performance of skulls of bats show a number of characteristic feeding adaptations. The great evening bat, Ia io (Thomas, 1902), eats both insects and birds (Thabah et al. J Mammal 88: 728-735, 2007), and as such, it is considered to represent a case of dietary niche expansion from insects to birds. How the skull morphology or bite force in I. io are related to the expanded diet (that is, birds) remains unknown. We used three-dimensional (3D) geometry of the skulls and measurements of bite force and diets from I. io and 13 other species of sympatric or closely related bat species to investigate the characteristics and the correlation of skull morphology and bite force to diets. RESULTS: Significant differences in skull morphology and bite force among species and diets were observed in this study. Similar to the carnivorous bats, bird-eaters (I. io) differed significantly from insectivorous bats; I. io had a larger skull size, taller crania, wider zygomatic arches, shorter but robust mandibles, and larger bite force than the insectivores. The skull morphology of bats was significantly associated with bite force whether controlling for phylogeny or not, but no significant correlations were found between diets and the skulls, or between diets and residual bite force, after controlling for phylogeny. CONCLUSIONS: These results indicated that skull morphology was independent of diet, and phylogeny had a greater impact on skull morphology than diet in these species. The changes in skull size and morphology have led to variation in bite force, and finally different bat species feeding on different foods. In conclusion, I. io has a larger skull size, robust mandibles, shortened dentitions, longer coronoid processes, expanded angular processes, low condyles, and taller cranial sagittal crests, and wider zygomatic arches that provide this species with mechanical advantages; their greater bite force may help them use larger and hard-bodied birds as a dietary component.

Magnetic solid phase extraction sorbents using methyl-parathion and quinalphos dual-template imprinted polymers coupled with GC-MS for class-selective extraction of twelve organophosphorus pesticides.

A novel magnetic dual-template molecularly imprinted polymer (DMIP) was prepared with methyl-parathion and quinalphos as templates. For comparison, a series of single-template polymers with only methyl-parathion (MPMIP) or quinalphos (QPMIP) as template as well as a non-imprinted polymer (NIP) in the absence of the template, were synthesized using the same procedure of DMIP. The obtained MIPs were characterized by scanning electron microscopy(SEM), Fourier transform infrared (FT-IR) spectroscopy, vibrating sample magnetometer (VSM), and X-ray diffraction (XRD). The properties including kinetic effect, thermodynamic effect, selectivity, and reusability of MIPs were investigated . Only DMIP possessed high affinity and good recognition for all twelve OPPs including quinalphos, isazophos, chlorpyrifos-methyl, chlorpyrifos, methidathion, triazophos, profenofos, fenthion, fenitrothion, methyl-parathion, parathion, and paraoxon in comparison to MPMIP, QPMIP, or NIP. Moreover, DMIP was used as magnetic solid phase extraction (MSPE) sorbent for the pre-concentration of twelve OPPs in cabbage samples. The developed DMIP-MSPE-GC-MS method showed high sensitivity, low LODs (1.62-13.9 ng/g), fast adsorption equilibrium (10 min), and acceptable spiked recoveries (81.5-113.4%) with relative standard deviations (RSD) in the range 0.05-7.0% (n = 3). The calibration plots were linear in the range 10-800 ng/mL with coefficients of determination (R2) better 0.99 for all twelve compounds. These results suggest that the DMIP is applicable for rapid determination and high throughput analysis of multi-pesticide residues. Graphical abstract.

Alendronate-Modified Polymeric Micelles for the Treatment of Breast Cancer Bone Metastasis.

Although the prognosis of patients with breast cancer continues to improve, breast cancer metastasis to bones remains high in incidence and challenging to manage. Here, we report the development of bone-homing alendronate (ALN)-anchored biodegradable polymeric micelles for the targeted treatment of metastatic cancer to bone. These micelles exhibited bone protective capacity including the recruitment, differentiation, and resorption activity of the osteoclasts. Encapsulation of docetaxel (DTX), the first-line chemotherapeutic for treatment of metastatic breast cancer, in ALN-modified micelles results in a sustained release, enhanced cytotoxicity, and improved pharmacokinetics. In the syngeneic animal model of late-stage disseminated breast cancer bone metastasis, the treatment with targeted DTX-loaded micelles attenuated the tumorigenesis and significantly improved animal lifespan compared to the conventional surfactant-based formulation (free DTX). These findings indicate potential applications of the osteotropic nanomedicines for bone metastasis treatment.

Engineering self-assembly of giant molecules in the condensed state based on molecular nanoparticles.

In biological systems, it is well-known that the activities and functions of biomacromolecules are dictated not only by their primary chemistries, but also by their secondary, tertiary, and quaternary hierarchical structures. Achieving control of similar levels in synthetic macromolecules is yet to be demonstrated. Most of the critical molecular parameters associated with molecular and hierarchical structures, such as size, composition, topology, sequence, and stereochemistry, are heterogenous, which impedes the exploration and understanding of structure formation and manipulation. Alternatively, in the past few years we have developed a unique giant molecule system based on molecular nanoparticles, in which the above-mentioned molecular parameters, as well as interactions, are precisely defined and controlled. These molecules could self-assemble into a myriad of unconventional and unique structures in the bulk, thin films, and solution. Giant molecules thus offer a robust platform to manipulate the hierarchical structures via precise and modular assemblies of building blocks in an amplified size level compared with small molecules. It has been found that they are not only scientifically intriguing, but also technologically relevant.

Sensitive Western-Blot Analysis of Azide-Tagged Protein Post Translational Modifications Using Thermoresponsive Polymer Self-Assembly.

Western-blot (WB) is a powerful analytical technique for protein identification in complex biological samples and has been widely used in biological studies for decades. Detection specificity and sensitivity of WB largely relies on quality of the antibodies and performance of the conjugated HRP. However, the application of WB analysis for the detection of protein post-translational modifications (PTMs) is hampered by the low abundance of protein PTMs and by the limited availability of antibodies that specifically differentiate various kinds of PTMs from their protein substrates. Therefore, new recognition mechanisms and signal amplification strategies for WB analysis of protein PTMs is in high demand. In this work, we prepared a soluble polymer that detects various azide-tagged PTM proteins in WB analysis using triarylphosphine and HRP modified thermoresponsive polymer. Specific and efficient detection of azide-tagged PTM protein is achieved via the bioorthogonal reaction between azide and triarylphosphine. More importantly, the chemiluminiscent signal in the WB analysis is largely amplified by the temperature induced self-assembly of numerous thermoresponsive polymer chains carrying multiple HRPs. As a result, approximately 100 times more sensitive detection than commercial antibodies is achieved by this method using standard PTM proteins. Though, this new reagent does not directly detect native PTMs in cell, tissue or blood samples, it still has important application potential in protein PTM studies, considering the wide availability of azide-tagging techniques to a variety of PTMs.

Potential protein biomarkers for burning mouth syndrome discovered by quantitative proteomics.

Burning mouth syndrome (BMS) is a chronic pain disorder characterized by severe burning sensation in normal looking oral mucosa. Diagnosis of BMS remains to be a challenge to oral healthcare professionals because the method for definite diagnosis is still uncertain. In this study, a quantitative saliva proteomic analysis was performed in order to identify target proteins in BMS patients' saliva that may be used as biomarkers for simple, non-invasive detection of the disease. By using isobaric tags for relative and absolute quantitation labeling and liquid chromatography-tandem mass spectrometry to quantify 1130 saliva proteins between BMS patients and healthy control subjects, we found that 50 proteins were significantly changed in the BMS patients when compared to the healthy control subjects ( p ≤ 0.05, 39 up-regulated and 11 down-regulated). Four candidates, alpha-enolase, interleukin-18 (IL-18), kallikrein-13 (KLK13), and cathepsin G, were selected for further validation. Based on enzyme-linked immunosorbent assay measurements, three potential biomarkers, alpha-enolase, IL-18, and KLK13, were successfully validated. The fold changes for alpha-enolase, IL-18, and KLK13 were determined as 3.6, 2.9, and 2.2 (burning mouth syndrome vs. control), and corresponding receiver operating characteristic values were determined as 0.78, 0.83, and 0.68, respectively. Our findings indicate that testing of the identified protein biomarkers in saliva might be a valuable clinical tool for BMS detection. Further validation studies of the identified biomarkers or additional candidate biomarkers are needed to achieve a multi-marker prediction model for improved detection of BMS with high sensitivity and specificity.

Crosslink Density Is Reduced and Oxidation Is Increased in Retrieved Highly Crosslinked Polyethylene TKA Tibial Inserts.

BACKGROUND: The wear resistance of highly crosslinked polyethylene depends on crosslink density, which may decrease with in vivo loading, leading to more wear and increased oxidation. The relationship among large and complex in vivo mechanical stresses, breakdown of the polyethylene crosslinks, and oxidative degradation is not fully understood in total knee arthroplasty (TKA). We wished to determine whether crosslink density is reduced at the articular surfaces of retrieved tibial inserts in contact areas exposed to in vivo mechanical stress. QUESTIONS/PURPOSES: (1) Does polyethylene crosslink density decrease preferentially in regions of the articular surface of thermally stabilized crosslinked polyethylene tibial components exposed to mechanical stress in vivo; and (2) what is the ramification of decreased crosslink density in TKA in terms of accompanying oxidation of the polyethylene? METHODS: From May 2011 to January 2014, 90 crosslinked polyethylene tibial components were retrieved during revision surgery as a part of a long-standing implant retrieval program. Forty highly crosslinked polyethylene tibial inserts (27 posterior-stabilized designs and 13 cruciate-retaining designs) retrieved for instability (15 cases), stiffness (11), infection (six), aseptic loosening (four), pain (two), and malposition (two) after a mean time of 18 months were inspected microscopically to identify loaded (burnished) and unloaded (unburnished) regions on the articular surfaces. Swell ratio testing was done according to ASTM F2214 to calculate crosslink density and infrared spectroscopy was used according to ASTM F2102 to measure oxidation. RESULTS: The region of the tibial insert influenced crosslink density. Loaded surface regions had a mean crosslink density of 0.19 (95% confidence interval [CI], 0.18-0.19) mol/dm3, lower than the other three regions (loaded subsurface, unloaded surface, and unloaded subsurface), which had crosslink densities of 0.21 (95% CI, 0.21-0.22; p < 0.01) mol/dm3. Peak oxidation levels were higher in loaded regions with a mean oxidation index (OI) of 0.67 (95% CI, 0.56-0.78) versus unloaded regions with a mean OI of 0.36 (95% CI, 0.27-0.45; p < 0.01). Peak oxidation levels were higher in annealed samples with a mean OI of 0.66 (95% CI, 0.52-0.81) versus remelted samples with a mean OI of 0.40 (95% CI, 0.34-0.47; p < 0.01). CONCLUSIONS: The results suggest that the crosslink density decreases and accompanying oxidation is driven predominantly by contact stress conditions. If crosslink density continues to decrease with continued loading over time, crosslinked polyethylene may not provide a clinical advantage over conventional polyethylene in the long term for TKA. Therefore, we will continue to collect longer term retrievals to evaluate mechanical property changes in crosslinked polyethylenes. CLINICAL RELEVANCE: Although we found a decrease in crosslink density and increase in oxidation in the tibial inserts, the degree of oxidation does not suggest, for now, a reason for concern in these early retrievals. The OI values of the tibial inserts in this study were lower than the critical oxidation level (OI > 3) reported in the literature where polyethylene may lose mechanical properties and have the compromised ability to withstand mechanical loading.

Effects of Structural Changes in Subchondral Bone on Articular Cartilage in a Beagle Dog Model.

OBJECTIVE: Using MR T2-mapping and histopathologic score for articular cartilage to evaluate the effect of structural changes in subchondral bone on articular cartilage. METHODS: Twenty-four male Beagle dogs were randomly divided into a subchondral bone defect group (n = 12) and a bone cement group (n = 12). Models of subchondral bone defectin the medial tibial plateau and subchondral bone filled with bone cement were constructed. In all dogs, the left knee joint was used as the experimental sideand the right knee as the sham side. The T2 value for articular cartilage at the medial tibial plateau was measured at postoperative weeks 4, 8, 16, and 24. The articular cartilage specimens were stained with hematoxylin and eosin, and evaluated using the Mankin score. RESULTS: There was a statistically significant difference (P < 0.05) in Mankin score between the bone defect group and the cement group at postoperative weeks 16 and 24. There was a statistically significant difference in the T2 values between the bone defect group and its sham group (P < 0.05) from week 8, and between the cement group and its sham group (P < 0.05) from week 16. There was significant difference in T2 values between the two experimental groups at postoperative week 24 (P < 0.01). The T2 value for articular cartilage was positively correlated with the Mankin score (ρ = 0.758, P < 0.01). CONCLUSION: Structural changes in subchondral bone can lead to degeneration of the adjacent articular cartilage. Defects in subchondral bone cause more severe degeneration of cartilage than subchondral bone filled with cement. The T2 value for articular cartilage increases with the extent of degeneration. MR T2-mapping images and the T2 value for articular cartilage can indicate earlycartilage degeneration.

Surface Damage Is Not Reduced With Highly Crosslinked Polyethylene Tibial Inserts at Short-term.

BACKGROUND: Highly crosslinked ultrahigh-molecular-weight polyethylene (XLPE) has been shown to reduce wear in hip arthroplasty, but the advantages over conventional polyethylene (PE) in total knee arthroplasty (TKA), if any, remain unclear. QUESTIONS/PURPOSES: Do differences exist in (1) surface damage as measured by damage score and percent area affected; and (2) extent and location of dimensional changes between XLPE and conventional PE observed on retrieved TKA tibial inserts? METHODS: In this study of components retrieved at the time of revision surgery, we matched 44 XLPE to 44 conventional PE inserts from four manufacturers; the matching approach considered implant design (exact match), insert size (exact match), and length of implantation (matched ± 6 months). Surface damage on the articular surfaces was subjectively graded and digitally mapped to determine the percent damaged area of each damage mode. Three-dimensional changes that had occurred as a result of implantation were determined by comparing laser scans of the retrieved inserts with size-matched pristine inserts. RESULTS: The differences of damage scores and percent damaged areas between the matched XLPE and conventional PE inserts were not large enough to be clinically significant with low corresponding levels of statistical significance (scores: 42 ± 13; 95% confidence interval [CI], 38-46 versus 45 ± 13; 95% CI, 41-49; p = 0.4; percent areas: 54% ± 38%; 95% CI, 44%-64% versus 54% ± 32%; 95% CI, 42%-65%; p = 0.9). However, XLPE inserts showed greater articular surface dimensional changes with high significance (root mean square of the distance: 0.16 ± 0.06 mm; 95% CI, 0.13-0.18 mm versus 0.14 ± 0.05 mm; 95% CI, 0.11-0.16 mm; p = 0.03). Within the same design, deviation patterns were consistent between the two materials; however, as expected, the location of the dimensional changes differed among designs: the negative deviations on the plateaus were centrally located in Zimmer PS inserts, were located on the perimeter in Smith & Nephew PS inserts, and were across the entire surface in DePuy PS inserts. CONCLUSIONS: We found no difference in surface damage between matched XLPE and conventional PE inserts of the same designs. However, increased dimensional changes in TKAs with XLPE may reflect larger contact areas and potentially explain improved performance of XLPE in published simulator studies. CLINICAL RELEVANCE: The lack of meaningful differences between the two polyethylene materials suggests caution in adopting a new, more expensive bearing material over another material that has a long track record of excellent behavior. A possible advantage is the greater dimensional changes, which could be the result of the lower creep resistance of XLPE, but this advantage awaits long-term results.

Differential accessibility of a rotavirus VP6 epitope in trimers comprising type I, II, or III channels as revealed by binding of a human rotavirus VP6-specific antibody.

Previous human antibody studies have shown that the human VH1-46 antibody variable gene segment encodes much of the naturally occurring human B cell response to rotavirus and is directed to virus protein 6 (VP6). It is currently unknown why some of the VH1-46-encoded human VP6 monoclonal antibodies inhibit viral transcription while others do not. In part, there are affinity differences between antibodies that likely affect inhibitory activity, but we also hypothesize that there are differing modes of binding to VP6 that affect the ability to block the transcriptional pore on double-layered particles. Here, we used a hybrid method approach for antibody epitope mapping, including single-particle cryo-electron microscopy (cryo-EM) and enhanced amide hydrogen-deuterium exchange mass spectrometry (DXMS) to determine the location and mode of binding of a VH1-46-encoded antibody, RV6-25. The structure of the RV6-25 antibody-double-layered particle (DLP) complex indicated a very complex binding pattern that revealed subtle differences in accessibility of the VP6 epitope depending on its position in the type I, II, or III channels. These subtle variations in the presentation or accessibility of the RV VP6 capsid layer led to position-specific differences in occupancy for binding of the RV6-25 antibody. The studies also showed that the location of binding of the noninhibitory antibody RV6-25 on the apical surface of RV VP6 head domain does not obstruct the transcription pore upon antibody binding, in contrast to binding of an inhibitory antibody, RV6-26, deeper in the transcriptional pore.

[Preliminarily analysis on traditional Chinese medicine advices in Treatise on Febrile Diseases].

To make a systematic analysis on literatures concerning traditional Chinese medicine (TCM) advices in Treatise on Febrile Diseases, and summarize the main connotations of traditional Chinese medicine advices, relevant TCM advices in Treatise on Febrile Diseases were collected, screened, compared, summarized and analyzed according to TCM dosage form preparation methods, TCM administration methods, medication contraindications and nursing after TCM administration. The literatures concerning medications in Treatise on Febrile Diseases were consulted, summarized and compared to standardize medicine advices and facilitate rational clinical application of TCMs. The standard medicine advices were as follows. The boiling water for TCMs shall be tap water and well water. The decoctions that have effects in promoting blood and meridians can be boiled with wine. The decoctions containing toxic components can be boiled with honey. Some TCMs shall be boiled with special methods, e. g. Herba Ephedra that could be boiled before other medicine and skimmed. Japonica rice could be added in decoctions to measure the duration of decoctions. Different dosages were required for different forms (litre, pill, medicine spoon). Administration times, temperature and frequency shall be adjusted according to target positions, functions and stage of illness. As for dietary contraindications during medication, thick porridges are recommended, where foods impacting medicine efficacy are prohibited. Regarding nursing after medication is important to recover physical functions, particularly warm porridges can go with diaphoretic recipes, while thick porridges can go with purgative recipes. And drug efficacies shall be defined by observing urine and excrements, and blood form. In conclusion, Treatise on Febrile Diseases is the first book that discusses TCM advices and records them in details. In this study, new standard medicine advices were proposed to provide important basis for improving clinical advices of TCMs and supports for developing the TCM dispensing technology.

Mechanical property of Ti6Al4V cylindrical porous structure for dental implants fabricated by selective laser melting.

The commonly used titanium alloy dental implants currently apply solid structures. However, issues such as stress shielding and stress concentration may arise due to the significant difference in elastic modulus between the implant and host. In order to address these problems, this paper proposes five porous structures based on the Gibson-Ashby theoretical model. We utilized selective laser melting technology to shape a porous structure using Ti-6Al-4V material precisely. The mechanical properties of the porous structure were verified through simulation and compression experiments. The optimal porous structure, which best matched the human bone, was a circular ring structure with a pillar diameter of 0.6 mm and a layer height of 2 mm. The stress and strain of the porous implant on the surrounding cortical and cancellous bone under different biting conditions were studied to verify the effectiveness of the optimal circular ring porous structure in alleviating stress shielding in both standard and osteoporotic bone conditions. The results confirm that the circular ring porous structure meets implant requirements and provides a theoretical basis for clinical dental implantation.