[Biomechanical study of three-dimensional printed filler block design in open wedge high tibial osteotomy].

The use of a filling block can improve the initial stability of the fixation plate in the open wedge high tibial osteotomy (OWHTO), and promote bone healing. However, the biomechanical effects of filling block structures and materials on OWHTO remain unclear. OWHTO anatomical filling block model was designed and built. The finite element analysis method was adopted to study the influence of six filling block structure designs and four different materials on the stress of the fixed plate, tibia, screw, and filling block, and the micro-displacement at the wedge gap of the OWHTO fixation system. After the filling block was introduced in the OWHTO, the maximum von Mises stress of the fixation plate was reduced by more than 30%, the maximum von Mises stress of the tibia decreased by more than 15%, and the lateral hinge decreased by 81%. When the filling block was designed to be filled in the posterior position of the wedge gap, the maximum von Mises stress of the fixation system was 97.8 MPa, which was smaller than other filling methods. The minimum micro-displacement of osteotomy space was -2.9 µm, which was larger than that of other filling methods. Compared with titanium alloy and tantalum metal materials, porous hydroxyapatite material could obtain larger micro-displacement in the osteotomy cavity, which is conducive to stimulating bone healing. The results demonstrate that OWHTO with a filling block can better balance the stress distribution of the fixation system, and a better fixation effect can be obtained by using a filling block filled in the posterior position. Porous HA used as the material of the filling block can obtain a better bone healing effect.

Tn antigen promotes breast cancer metastasis via impairment of CASC4.

Breast cancer is one of the most serious and deadly cancers in women worldwide, with distant metastases being the leading cause of death. Tn antigen, a tumor-associated carbohydrate antigen, was frequently detected in breast cancer, but its exact role in breast cancer metastasis has not been well elucidated. Here we investigated the impact of Tn antigen expression on breast cancer metastasis and its underlying mechanisms. The expression of Tn antigen was induced in two breast cancer cell lines by deleting T-synthase or Cosmc, both of which are required for normal O-glycosylation. It showed that Tn-expressing cancer cells promoted epithelial-mesenchymal transition (EMT) and metastatic features as compared to Tn(-) control cells both in vitro and in vivo. Mechanistically, we found that cancer susceptibility candidate 4 (CASC4), a heavily O-glycosylated protein, was significantly downregulated in both Tn(+) cells. Overexpression of CASC4 suppressed Tn-induced activation of EMT and cancer metastasis via inhibition of Cdc42 signaling. Furthermore, we confirmed that O-glycosylation is essential for the functional role of CASC4 because defective O-glycosylated CASC4 (mutant CASC4, which lacks nine O-glycosylation sites) exerted marginal metastatic-suppressing effects in comparison with WT CASC4. Collectively, these data suggest that Tn-mediated aberrant O-glycosylation contributes to breast cancer metastasis via impairment of CASC4 expression and function.

[Origin, development, and modern application value of Chinese herbal lozenges].

Lozenge is one of the traditional dosage forms of Chinese medicine. It has been recorded in traditional Chinese medical classics of all dynasties since the Eastern Han Dynasty and has been developing and evolving continuously. The unique pharmaceutical methods and application scope are the driving force of its emergence, existence, and development. Up to now, lozenge has been included in the Chinese Pharmacopoeia as an independent dosage form. Lozenge has been endowed with new meaning by modern Chinese medicine pharmaceutics, which is worth tracing origin and exploring value. The present study reviewed the origin and development of lozenge, compared lozenge with other similar dosage forms, analyzed the characteristics of modern and ancient dosage forms of lozenge, and discussed the development prospect and potential of lozenge in combination with the demand development of modern Chinese medicine preparation, so as to provide references for expanding the modern application of lozenge.

[Textual research on medicinal blue herbs].

In this paper, through the collection and collation of ancient herbs, medical books and prescriptions, combined with modern literature, the historical changes of the name, origin, position, medicinal parts, collection, processing and processing of bluegrass were systematically combed and verified.It can be seen from the research that bluegrass was first used as medicine by the fruit, namely blueberry, which was originally Polygonum tinctorium. Since the Ming and Qing Dynasties, blueberry was rarely used, and it has been no longer used medicinally. In the Wei and Jin Dynasties, the medicinal parts extended to the stems and leaves, and most of them used juice as medicine.Since the Tang Dynasty, origin has been extended to Isatis indigotica, Baphicacanthus cusia, Indigofera tinctoria, Compositae plant Wulan, etc. In the Song Dynasty, the medicinal parts extended to the roots, and the "Banlangen" began to appear, and gradually became the main medicinal parts of blue medicinal materials, the main base of which was B. cusia. Since the Qing Dynasty, I. indigotica, a Cruciferae, has gradually become a genuine indigo root, while B. cusia has become a southern indigo root. It was the first mineral dye imported from abroad for thrush, and then used as medicine, also known as clam powder. Because it was found that it had the same effect with the extract of bluegrass, it was also named indigo naturalis in China, which has lasted till now. The main stream of Isatidis Folium in the past dynasties is the dry stem and leaf of Clerodendrum cyrtophylum. Since the Qing Dynasty, the stem and leaf of Isatis indigotica, P. tinctorium and other blue grasses have been gradually mixed as substitutes and gradually become the mainstream.

A first porphyrin liquid crystal with strong fluorescence in both solution and aggregated states based on the AIE-FRET effect.

Porphyrins are good near-infrared fluorescent materials, but the strong self-assembly stacking resulted in the aggregation-caused quenching (ACQ) effect, limiting their emissive performance in aggregated states. In this work, a novel diphenylacrylonitrile-porphyrin derivative with multiple polyglycol chains on the periphery was designed and synthesized as an excellent near-infrared-emissive liquid crystalline material in both solution and aggregated states, which was first observed for porphyrin liquid crystals. It exhibited a high self-assembly ability with the ordered hexagonal columnar mesophase between 70 and 120 °C approximately. The strong AIE-FRET effect was produced based on the overlap of the emission wavelength of diphenylacrylonitrile and the absorption wavelength of the porphyrin, resulting in the excellent near-infrared emission in both solution and aggregated states. The pseudo Stokes shift was as large as 210 nm and the fluorescence quantum yield reached 0.12 in the solid state. Moreover, this porphyrin liquid crystal displayed low biotoxicity and excellent fluorescence bio-imaging ability in living cells, opening a new application prospect for porphyrin liquid crystalline materials.

[Nasal submicron emulsion of Scutellariae Radix extract preparation technology research based on phase transfer of solute technology].

Based on the demand of nasal drug delivery high drug loadings, using the unique phase transfer of solute, integrating the phospholipid complex preparation and submicron emulsion molding process of Scutellariae Radix extract, the study obtained the preparation of the high drug loadings submicron emulsion of Scutellariae Radix extract. In the study of drug solution dispersion method, the uniformity of drug dispersed as the evaluation index, the traditional mixing method, grinding, homogenate and solute phase transfer technology were investigated, and the solute phase transfer technology was adopted in the last. With the adoption of new technology, the drug loading capacity reached 1.33% (phospholipid complex was 4%). The drug loading capacity was improved significantly. The transfer of solute method and timing were studied as follows,join the oil phase when the volume of phospholipid complex anhydrous ethanol solution remaining 30%, the solute phase transfer was completed with the continued recycling of anhydrous ethanol. After drug dissolved away to oil phase, the preparation technology of colostrum was determined with the evaluation index of emulsion droplet form. The particle size of submicron emulsion, PDI and stability parameters were used as evaluation index, orthogonal methodology were adopted to optimize the submicron emulsion ingredient and main influential factors of high pressure homogenization technology. The optimized preparation technology of Scutellariae Radix extract nasal submicron emulsion is practical and stable.

Tibial post loading increases the risk of aseptic loosening of posterior-stabilized tibial prosthesis.

Aseptic loosening is the primary cause of failure following posterior-stabilized total knee arthroplasty. It is unclear whether tibial post loading of posterior-stabilized prosthesis increases the risk of aseptic loosening of the tibial prosthesis. The purpose of this study is to investigate the biomechanical effects of tibial post loading on the tibial prosthesis fixation interface during level walking, squatting, stair descent, and standing up-sitting down activities. In this paper, finite element models with and without post were established to compare the effects of tibial post loading on the von Mises stress of the proximal tibia, shear stress of the cement, and the bone-prosthesis interface micromotion during four physiological activities. The tibial post loading had an insignificant influence on tibial biomechanics and bone-prosthesis interface micromotion during leveling walking activity. However, compared to the insert without post condition, tibial post loading significantly increased the maximum tibial von Mises stress, the maximum shear stress in the medial of cement, and the bone-prosthesis interface peak micromotion by 912.84%, 612.77%, and 921.09%, respectively, at the moment of the maximum flexion angle for the stair descent activity, and 637.92%, 351.43%, and 519.13%, respectively, at the moment of the maximum flexion angle for the standing up-sitting down activity. Tibial post loading increased the risk of postoperative aseptic loosening of tibial prosthesis in patients with posterior-stabilized total knee arthroplasty, and it was recommended that the post-cam contact mechanism of posterior-stabilized prosthesis should be optimized to reduce the biomechanical impact of tibial post loading on tibial prosthesis fixation.

Clinical relevance of RNA editing profiles in lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is the most frequently occurring lung cancer worldwide, with increasing death rates. It belongs to the non-small cell lung cancer (NSCLC) type and has a strong association with previous smoking history. Growing evidence has demonstrated the significance of adenosine-to-inosine RNA editing (ATIRE) dysregulation in cancer. The aim of the present study was to evaluate ATIRE events that might be clinically useful or tumorigenic. Methods: To explore survival-related ATIRE events in LUAD, its ATIRE profiles, gene expression data, and corresponding patients' clinical information were downloaded from the Cancer Genome Atlas (TCGA) and the synapse database. We evaluated 10441 ATIRE in 440 LUAD patients from the TCGA database. ATIRE profiles were merged with TCGA survival data. We selected prognostic ATIRE sites, using a univariate Cox analysis (p < 0.001). Cox proportional hazards regression and lasso regression analysis were used to determine survival-related ATIRE sites, create risk ratings for those sites, and build a prognostic model and a nomogram for assessing overall survival (OS). Six ATIRE sites were used in the prognostic model construction and patients were randomly divided into a validation cohort (n = 176) and a training cohort (n = 264). The "Pheatmap" program was used to create risk curves that included risk score, survival time, and expression of ATIRE sites. We also determined the clinical prediction model's discrimination. The decision curve analysis and the 1-, 2-, and 3-year corrective curves were simultaneously used to evaluate the nomogram. We also evaluated the relationship between the amount of ATIRE sites and host gene expression and the impact of ATIRE expression on transcriptome expression. Results: The pyroglutamyl-peptidase I (PGPEP1) chr19:18476416A > I, ankyrin repeat domain 36B pseudogene 1 (ANKRD36BP1) (dist = 3,795), T-box transcription factor (TBX19) (dist = 29815) chr1:168220463A > I, Syntrophin Beta 2 (SNTB2) chr16:69338598A > I, hook microtubule-tethering protein 3 (HOOK3) chr8:42883441A > I, NADH dehydrogenase flavoprotein 3 (NDUFV3) chr21:44329452A > I, and FK506-binding protein 11 (FKBP11) chr12:49316769A > I were used in the prognostic model construction. High levels of risk score were significantly associated with worse OS and progression-free survival. Tumour stage and risk score were related to OS in LUAD patients. The predictors were among the prognostic nomogram model's risk score, age, gender, and tumor stage. The calibration plot and C-index (0.718) demonstrated the significant accuracy of nomogram's predictions. ATIRE level was markedly elevated in tumor tissues and was highly variable between patients. Conclusion: Events involving ATIRE in LUAD were highly functional and clinically relevant. The RNA editing-based model provides a solid framework for further investigation of the functions of RNA editing in non-coding areas and may be used as a unique method for predicting LUAD survival.

Influence of plastic aggregate geometry on strength properties of cement-stabilized macadam.

In order to improve the toughness and flexibility of cement-stabilized macadam and inhibit crack formation and propagation, the influence of plastic aggregate geometry on the strength properties of cement-stabilized macadam is studied. The surface roughness of plastic aggregate was designed into Ra 12.5 and Ra 25. When the content of plastic coarse aggregate was gradually increased from 4 to 8%, 12%, 16%, 20%, and 24%, the compressive strength, splitting strength, and the tensile-compression ratio of the cement-stabilized macadam made of aggregate with rough surface texture were found higher than those of aggregate with smooth surface texture. The rough cylindrical, spherical, spindle, and dumbbell-shaped plastic coarse aggregates were designed and prepared for testing. The test results showed the maximum compressive strength, splitting strength, and tensile-compression ratio of cement-stabilized macadam with the dumbbell-shaped plastic coarse aggregate. The tensile-compression ratio increased by 15.2% compared to natural aggregate cement-stabilized macadam. The results show that under the same conditions, the plastic aggregate with different geometry can improve the compressive and splitting strengths of cement-stabilized macadam and significantly improve the toughness and flexibility, with dumbbell-shaped plastic coarse aggregate having the greatest improvement, especially compared with natural aggregate cement-stabilized crushed stone. This research provides insights for improving pavement engineering quality and new ideas for utilizing waste plastics.

Dysfunctional O-glycosylation exacerbates LPS-induced ARDS in mice through impairment of podoplanin expression on alveolar macrophages.

O-glycosylation is one of the most common post-translational modifications of proteins, which participates in immune cell recognition, activation, and surveillance. Alveolar macrophage (AM) is closely involved in the pathogenesis of acute respiratory distress syndrome (ARDS), which is associated with excessive, uncontrolled inflammatory response. It is unclear whether and how O-glycosylation affects AM activation as well as ARDS. Here, we administrated experimental mice with an O-glycosylation inhibitor (benzyl-α-GalNAc) at 5 or 10 mg/kg 24 h before intratracheal instillation of LPS (1 mg/kg). At 6 h and 12 h after LPS challenge, mice were sacrificed to collect samples for further analysis. The results showed that benzyl-α - GalNAc induced abundant expression of the Tn antigen, which is a typical marker for abnormal O-glycosylation. Benzyl-α-GalNAc pretreatment significantly exacerbated LPS-induced inflammatory damage in lungs, evidenced by more severe histological signs and drastic elevation of multiple inflammatory cytokines. Mechanistically, benzyl-α-GalNAc impaired podoplanin expression on AMs in mice, which is a heavily O-glycosylated protein that mediates anti-inflammation responses, whereas adoptive transfer of podoplanin-expressing macrophages alleviated LPS-induced ARDS in mice. This study demonstrated that benzyl-α-GalNAc-induced inhibition of O-glycosylation aggravated LPS-induced ARDS in mice, which may be due to down-regulation of podoplanin expression on AMs. We therefore suggest that podoplanin on AMs is essential for lung protection.

Scutellaria baicalensis Extract-phospholipid Complex: Preparation and Initial Pharmacodynamics Research in Rats.

BACKGROUND: Baicalin, a flavonoid glycoside compound present in Scutellaria baicalensis, has shown a wide spectrum of biological activities, but its liposolubility, water-solubility and mucosal permeability are all very poor, which leads to the low concentration in brain and poor bioavailability by oral or intravenous injective administration. OBJECTIVE: The primary objective of this study was to formulate the Scutellaria baicalensis extract (SBE) with phospholipid to yield Scutellaria baicalensis extract-phospholipid complex (SBEPC) , and to evaluate its pharmacodynamics in the middle cerebral artery occlusion (MCAO). METHODS: The optimal preparation technology of SBEPC was obtained through single-factor test and central composite design-response surface methodology (CCD-RSM), and was characterized with various analytical techniques including SEM, FT-IR and NMR. The storage conditions of SBEPC were established through stability study and the MCAO rat model was investigated through conducting pharmacodynamic studies to screen the appropriate administration and dose of SBEPC as well as to verify the neuroprotective effect of SBEPC on cerebral ischemia-reperfusion injury. RESULTS: The optimized preparation conditions of SBEPC were summarized as follows: the ratio of phospholipids to drug was 2:1, the drug concentration was 3.5 mg/ml, the reaction temperature was 50 °C, and the entrapment efficiency was over 93.00%. Stability studies have demonstrated that SBEPC should be stored under 40 °C in a dry and ventilated place away from light and below 37% humidity. Furthermore, pharmacodynamic studies have found that, compared with SBE, SBEPC could introduce drugs into the brain and better exert the neuroprotective effect on MCAO rats, and the optimal administration and dose concentration of SBEPC were nasal administration and 40 mg/ml, respectively. CONCLUSION: These findings demonstrate that SBEPC is successfully prepared by CCD-RSM. SBEPC can enhance drugs' ability to enter the brain and improve the bioavailability of drugs in brain, and can effectively exert the neuroprotective effect on cerebral ischemia-reperfusion injury as compared with SBE.

Targeting MDK Abrogates IFN-γ-Elicited Metastasis inCancers of Various Origins.

IFN-γ is a pleiotropic cytokine with immunomodulatory and tumoricidal functions. It has been used as an anti-tumor agent in adjuvant therapies for various cancers. Paradoxically, recent advances have also demonstrated pro-tumorigenic effects of IFN-γ, especially in promoting cancer metastasis, with the mechanism remains unclear. This will undoubtedly hinder the application of IFN-γ in cancer treatment. Here, we verified that IFN-γ treatment led to activation of the epithelial-to-mesenchymal transition (EMT) programme and metastasis in cell lines of various cancers, including the kidney cancer cell line Caki-1, the lung cancer cell line A549, the cervical carcinoma cell line CaSki, the breast cancer cell line BT549 and the colon cancer cell line HCT116. We further disclosed that midkine (MDK), an emerging oncoprotein and EMT inducer, is a common responsive target of IFN-γ in these cell lines. Mechanistically, IFN-γ upregulated MDK via STAT1, a principle downstream effector in the IFN-γ signalling. MDK is elevated in the majority of cancer types in the TCGA database, and its overexpression drove EMT activation and cancer metastasis in all examined cell lines. Targeting MDK using a specific MDK inhibitor (iMDK) broadly reversed IFN-γ-activated EMT, and subsequently abrogated IFN-γ-triggered metastasis. Collectively, our data uncover a MDK-dependent EMT inducing mechanism underlying IFN-γ-driven metastasis across cancers which could be attenuated by pharmacological inhibition of MDK. Based on these findings, we propose that MDK may be used as a potential therapeutic target to eliminate IFN-γ-elicited pro-metastatic adverse effect, and that combined MDK utilization may expand the application of IFN-γ in cancer and improve the clinical benefits from IFN-γ-based therapies.

S100A12 as Biomarker of Disease Severity and Prognosis in Patients With Idiopathic Pulmonary Fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) is one of interstitial lung diseases (ILDs) with poor prognosis. S100 calcium binding protein A12 (S100A12) has been reported as a prognostic serum biomarker in the IPF, but its correlation with IPF remains unclear in the lung tissue and bronchoalveolar lavage fluids (BALF). Methods: Datasets were collected from the Gene Expression Omnibus (GEO) database. Person correlation coefficient, Kaplan-Meier analysis, Cox regression analysis, functional enrichment analysis and so on were used. And single cell RNA-sequencing (scRNA-seq) analysis was also used to explore the role of S100A12 and related genes in the IPF. Results: S100A12 was mainly and highly expressed in the monocytes, and its expression was downregulated in the lung of patients with IPF according to scRNA-seq and the transcriptome analysis. However, S100A12 expression was upregulated both in blood and BALF of patients with IPF. In addition, 10 genes were found to interact with S100A12 according to protein-protein interaction (PPI) network, and the first four transcription factors (TF) targeted these genes were found according to hTFtarget database. Two most significant co-expression genes of S100A12 were S100A8 and S100A9. The 3 genes were significantly negatively associated with lung function and positively associated with the St. George's Respiratory Questionnaire (SGRQ) scores in the lung of patients with IPF. And, high expression of the 3 genes was associated with higher mortality in the BALF, and shorter transplant-free survival (TFS) and progression-free survival (PFS) time in the blood. Prognostic predictive value of S100A12 was more superior to S100A8 and S100A9 in patients with IPF, and the composited variable [S100A12 + GAP index (gender, age, and physiological index)] may be a more effective predictive index. Conclusion: These results imply that S100A12 might be an efficient disease severity and prognostic biomarker in patients with IPF.

CD247, a Potential T Cell-Derived Disease Severity and Prognostic Biomarker in Patients With Idiopathic Pulmonary Fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) has high mortality worldwide. The CD247 molecule (CD247, as known as T-cell surface glycoprotein CD3 zeta chain) has been reported as a susceptibility locus in systemic sclerosis, but its correlation with IPF remains unclear. Methods: Datasets were acquired by researching the Gene Expression Omnibus (GEO). CD247 was identified as the hub gene associated with percent predicted diffusion capacity of the lung for carbon monoxide (Dlco% predicted) and prognosis according to Pearson correlation, logistic regression, and survival analysis. Results: CD247 is significantly downregulated in patients with IPF compared with controls in both blood and lung tissue samples. Moreover, CD247 is significantly positively associated with Dlco% predicted in blood and lung tissue samples. Patients with low-expression CD247 had shorter transplant-free survival (TFS) time and more composite end-point events (CEP, death, or decline in FVC >10% over a 6-month period) compared with patients with high-expression CD247 (blood). Moreover, in the follow-up 1st, 3rd, 6th, and 12th months, low expression of CD247 was still the risk factor of CEP in the GSE93606 dataset (blood). Thirteen genes were found to interact with CD247 according to the protein-protein interaction network, and the 14 genes including CD247 were associated with the functions of T cells and natural killer (NK) cells such as PD-L1 expression and PD-1 checkpoint pathway and NK cell-mediated cytotoxicity. Furthermore, we also found that a low expression of CD247 might be associated with a lower activity of TIL (tumor-infiltrating lymphocytes), checkpoint, and cytolytic activity and a higher activity of macrophages and neutrophils. Conclusion: These results imply that CD247 may be a potential T cell-derived disease severity and prognostic biomarker for IPF.

Effect of Rotator Cuff Deficiencies on Muscle Forces and Glenohumeral Contact Force After Anatomic Total Shoulder Arthroplasty Using Musculoskeletal Multibody Dynamics Simulation.

Anatomic total shoulder arthroplasty (ATSA) is widely used to treat the diseases of the glenohumeral (GH) joint. However, the incidence of rotator cuff tears after ATSA increases during follow-up. The effects of rotator cuff deficiencies after ATSA on the biomechanics of the GH joint are to be investigated. In this study, a musculoskeletal multibody dynamics model of ATSA was established using a force-dependent kinematics (FDK) method. The biomechanical effects were predicted during arm abduction under different rotator cuff deficiencies. The deltoid forces were increased under the rotator cuff deficiencies, the maximum deltoid forces were increased by 36% under the subscapularis deficiency and by 53% under the supraspinatus, infraspinatus, subscapularis, and teres minor deficiencies. The maximum GH contact forces were decreased by 11.3% under supraspinatus and infraspinatus deficiencies but increased by 24.8% under subscapularis deficiency. The maximum subscapularis force was decreased by 17% under only infraspinatus tear during arm abduction. The results suggested that the changes in the biomechanics of the GH joint induced by rotator cuff deficiencies after ATSA increase the deltoid muscle energy expenditure and joint instability, which result in postoperative less satisfactory clinical outcomes. The changes in rotator cuff muscle forces deserve more attention for understanding the evolution of rotator cuff tear after ATSA.

SLC15A4 Serves as a Novel Prognostic Biomarker and Target for Lung Adenocarcinoma.

BACKGROUND: SLC15A family members are known as electrogenic transporters that take up peptides into cells through the proton-motive force. Accumulating evidence indicates that aberrant expression of SLC15A family members may play crucial roles in tumorigenesis and tumor progression in various cancers, as they participate in tumor metabolism. However, the exact prognostic role of each member of the SLC15A family in human lung cancer has not yet been elucidated. MATERIALS AND METHODS: We investigated the SLC15A family members in lung cancer through accumulated data from TCGA and other available online databases by integrated bioinformatics analysis to reveal the prognostic value, potential clinical application and underlying molecular mechanisms of SLC15A family members in lung cancer. RESULTS: Although all family members exhibited an association with the clinical outcomes of patients with NSCLC, we found that none of them could be used for squamous cell carcinoma of the lung and that SLC15A2 and SLC15A4 could serve as biomarkers for lung adenocarcinoma. In addition, we further investigated SLC15A4-related genes and regulatory networks, revealing its core molecular pathways in lung adenocarcinoma. Moreover, the IHC staining pattern of SLC15A4 in lung adenocarcinoma may help clinicians predict clinical outcomes. CONCLUSION: SLC15A4 could be used as a survival prediction biomarker for lung adenocarcinoma due to its potential role in cell division regulation. However, more studies including large patient cohorts are required to validate the clinical utility of SLC15A4 in lung adenocarcinoma.

Caffeine and dithiothreitol delay ovine oocyte ageing.

The intracellular glutathione levels and developmental competence of aged oocytes after parthenogenetic activation, somatic cell nuclear transfer and intracytoplasmic sperm injection in the presence or absence of caffeine or dithiothreitol (DTT) were examined. The following results were found: (1) ovine oocytes were fully aged 30 h post-onset of maturation culture; (2) the appropriate concentrations of caffeine and DTT for oocyte culture were 5 mM and 1 mM, respectively; (3) when nuclear transfer-reconstructed embryos were treated with caffeine or DTT following fusion, no increase in the frequency of development to blastocyst was observed (P > 0.05), but the cell numbers of blastocysts increased (P < 0.05); (4) both caffeine and DTT increased the blastocyst formation rates of intracytoplasmic sperm-injected embryos (P < 0.05); (5) caffeine increased the glutathione content of aged oocytes (P < 0.05). The glutathione content of DTT-treated aged oocytes was higher than that of oocytes matured for 36 h (P < 0.05). In conclusion, caffeine and dithiothreitol delay oocyte ageing but only to a limited extent.

Effects of Daily Activities and Position on Kinematics and Contact Mechanics of Dual Mobility Hip Implant.

Dual mobility hip implants have been widely introduced to overcome dislocation in recent years. However, the potential influence of different gaits on kinematics and contact mechanics for dual mobility hip implants is still unclear. Furthermore, a large range of motion coupling with the implant position, especially high inclination or anteversion angle, may result in poor kinematics and contact mechanics. A previously developed dynamic finite element method was adopted in this study to examine the kinematics and corresponding stability of dual mobility hip implants under different gaits coupling with different inclinations or anteversion angles. The results showed only inner relative sliding under knee-bending for dual mobility hip implants under moderate inclination and anteversion angles, whereas an anteversion angle of 25° induced both impingement and consequent relative sliding of the outer articulation. However, the impingement (between the stem neck and the liner inner rim) indeed happened under stair-climbing and sitting-down/stand-up as well as combined movements when inclination and anteversion angles were set as 45° and 0°, respectively, and this finally led to relative sliding at the outer articulation. A high inclination angle did not worsen both the impingement and related outer sliding compared to modest inclination and anteversion angles of the liner, but a high anteversion angle prolonged the period of both the impingement and the outer relative sliding. The extreme motions and high anteversion angles are hardly inevitable, and they indeed lead to motions at both articulations for dual mobility hip implants.

Achieving GWAS with homomorphic encryption.

BACKGROUND: One way of investigating how genes affect human traits would be with a genome-wide association study (GWAS). Genetic markers, known as single-nucleotide polymorphism (SNP), are used in GWAS. This raises privacy and security concerns as these genetic markers can be used to identify individuals uniquely. This problem is further exacerbated by a large number of SNPs needed, which produce reliable results at a higher risk of compromising the privacy of participants. METHODS: We describe a method using homomorphic encryption (HE) to perform GWAS in a secure and private setting. This work is based on a proposed algorithm. Our solution mainly involves homomorphically encrypted matrix operations and suitable approximations that adapts the semi-parallel GWAS algorithm for HE. We leverage upon the complex space of the CKKS encryption scheme to increase the number of SNPs that can be packed within a ciphertext. We have also developed a cache module that manages ciphertexts, reducing the memory footprint. RESULTS: We have implemented our solution over two HE open source libraries, HEAAN and SEAL. Our best implementation took 24.70 minutes for a dataset with 245 samples, over 4 covariates and 10643 SNPs. CONCLUSIONS: We demonstrate that it is possible to achieve GWAS with homomorphic encryption with suitable approximations.

An Experimental Study on the Precision Abrasive Machining Process of Hard and Brittle Materials with Ultraviolet-Resin Bond Diamond Abrasive Tools.

Ultraviolet-curable resin was introduced as a bonding agent into the fabrication process of precision abrasive machining tools in this study, aiming to deliver a rapid, flexible, economical, and environment-friendly additive manufacturing process to replace the hot press and sintering process with thermal-curable resin. A laboratory manufacturing process was established to develop an ultraviolet-curable resin bond diamond lapping plate, the machining performance of which on the ceramic workpiece was examined through a series of comparative experiments with slurry-based iron plate lapping. The machined surface roughness and weight loss of the workpieces were periodically recorded to evaluate the surface finish quality and the material removal rate. The promising results in terms of a 12% improvement in surface roughness and 25% reduction in material removal rate were obtained from the ultraviolet-curable resin plate-involved lapping process. A summarized hypothesis was drawn to describe the dynamically-balanced state of the hybrid precision abrasive machining process integrated both the two-body and three-body abrasion mode.