Mitochondrial Protease Oct1p Regulates Mitochondrial Homeostasis and Influences Pathogenicity through Affecting Hyphal Growth and Biofilm Formation Activities in Candida albicans.

Mitochondria, as the core metabolic organelles, play a crucial role in aerobic respiration/biosynthesis in fungi. Numerous studies have demonstrated a close relationship between mitochondria and Candida albicans virulence and drug resistance. Here, we report an octapeptide-aminopeptidase located in the mitochondrial matrix named Oct1p. Its homolog in the model fungus Saccharomyces cerevisiae is one of the key proteins in maintaining mitochondrial respiration and protein stability. In this study, we utilized evolutionary tree analysis, gene knockout experiments, mitochondrial function detection, and other methods to demonstrate the impact of Oct1p on the mitochondrial function of C. albicans. Furthermore, through transcriptome analysis, real-time quantitative PCR, and morphological observation, we discovered that the absence of Oct1p results in functional abnormalities in C. albicans, affecting hyphal growth, cell adhesion, and biofilm formation. Finally, the in vivo results of the infection of Galleria mellonella larvae and vulvovaginal candidiasis in mice indicate that the loss of Oct1p led to the decreased virulence of C. albicans. In conclusion, this study provides a solid theoretical foundation for treating Candida diseases, developing new targeted drugs, and serves as a valuable reference for investigating the connection between mitochondria and virulence in other pathogenic fungi.

Exercise-mediated macrophage polarization modulates the targeted therapeutic effect of NAFLD: a review.

PURPOSE: This review aims to explore the exercise-mediated hepatic macrophage polarization mechanism and its effect on improving and regulating non-alcoholic fatty liver disease (NAFLD) by analyzing the pathogenesis of NAFLD and the cause of the influence of hepatic macrophage polarization. In addition to exploring the varied effects of different exercise types on macrophage polarization regulation in NAFLD, to provide a direction and basis for the treatment of NAFLD. METHODS: The research methodology involved a comprehensive search of the PubMed database using specific keywords such as "NAFLD", "macrophage polarization", and "exercise", to retrieve relevant literature published. RESULTS: (1) The main factors inducing NAFLD were high-fat diet, obesity, insulin resistance (IR), changes in gut microbiota, and genetic variation in susceptibility. (2) Drug treatment, nutrient induction, microfactor induction, physiological environment induction, and other factors can induce the polarization of hepatic macrophages and affect NAFLD. (3) Different intensities, types, and frequencies of exercise have different effects on polarization macrophages, and may also differently effects improving liver inflammation, fibrosis, and NAFLD. Curently, regular moderate-intensity aerobic exercise is the most effective therapy for treating NAFLD. CONCLUSION: Approaches to ameliorate NAFLD with exercise involve strategies to alter macrophage polarization by inhibiting M1 or driving M2 activation. However, research on the different types of exercise-mediated macrophage polarization mechanisms and differences in therapeutic effects is not yet sufficient. Future research is necessary to explore the exact mechanisms and differences in the effects of different exercises on the treatment of NAFLD.

Gut microbiota contributes to lignocellulose deconstruction and nitrogen fixation of the larva of Apriona swainsoni.

Apriona swainsoni is a vital forest pest prevalent in China. The larvae of A. swainsoni live solely in the branches of trees and rely entirely on the xylem for nutrition. However, there is still a lack of in-depth research on the gut microbiota's use of almost nitrogen-free wood components to provide bio-organic macromolecular components needed for their growth. Thus, in this study, the metagenome, metaproteome, and metabolome of the A. swainsoni larvae in four gut segments (foregut; midgut; anterior hindgut; posterior hindgut) were analyzed by the multi-omics combined technology, to explore the metabolic utilization mechanism of the corresponding gut microbiota of A. swainsoni. Firstly, we found that the metagenome of different gut segments was not significantly different in general, but there were different combinations of dominant bacteria and genes in different gut segments, and the metaproteome and metabolome of four gut segments were significantly different in general. Secondly, the multi-omics results showed that there were significant gradient differences in the contents of cellulose and hemicellulose in different segments of A. swainsoni, and the expression of corresponding metabolic proteins was the highest in the midgut, suggesting the metabolic characteristics of these lignocellulose components in A. swainsoni gut segments. Finally, we found that the C/N ratio of woody food was significantly lower than that of frass, and metagenomic results showed that nitrogen fixation genes mainly existed in the foregut and two hindgut segments. The expression of the key nitrogen fixing gene nifH occurred in two hindgut parts, indicating the feature of nitrogen fixation of A. swainsoni. In conclusion, our results provide direct evidence that the larvae of A. swainsoni can adapt to the relatively harsh niche conditions through the highly organized gut microbiome in four gut segments, and may play a major role in their growth.

3D-printed mesoporous bioactive glass/GelMA biomimetic scaffolds for osteogenic/cementogenic differentiation of periodontal ligament cells.

Integrated regeneration of periodontal tissues remains a challenge in current clinical applications. Due to the tunable physical characteristics and the precise control of the scaffold microarchitecture, three-dimensionally (3D) printed gelatin methacryloyl (GelMA)-based scaffold has emerged as a promising strategy for periodontal tissue regeneration. However, the optimization of the printing biomaterial links the formulation and the relationship between the composition and structures of the printed scaffolds and their comprehensive properties (e.g. mechanical strength, degradation, and biological behaviors) remains unclear. Here, in this work, a novel mesoporous bioactive glass (BG)/GelMA biomimetic scaffold with a large pore size (∼300 µm) was developed by extrusion-based 3D printing. Our results showed that the incorporation of mesoporous bioactive glass nanoparticles (BG NPs) significantly improved shape fidelity, surface roughness, and bioactivity of 3D-printed macroporous GelMA scaffolds, resulting in the enhanced effects on cell attachment and promoting osteogenic/cementogenic differentiation in human periodontal ligament cells. The excellent maintenance of the macropore structure, the visibly improved cells spreading, the release of bioactive ions (Si4+, Ca2+), the upregulation of gene expressions of osteogenesis and cementogensis, and the increase in alkaline phosphatase (ALP) activity and calcium nodules suggested that BG NPs could endow GelMA-based scaffolds with excellent structural stability and the ability to promote osteogenic/cementogenic differentiation. Our findings demonstrated the great potential of the newly formulated biomaterial inks and biomimetic BG/GelMA scaffolds for being used in periodontal tissue regeneration and provide important insights into the understanding of cell-scaffold interaction in promoting the regeneration of functional periodontal tissues.

Sodium houttuyfonate effectively treats acute pulmonary infection of Pseudomonas aeruginosa by affecting immunity and intestinal flora in mice.

Introduction: Pseudomonas aeruginosa is a major nosocomial pathogen that frequently causes ventilator-associated pneumonia in specific populations. Sodium houttuyfonate (SH) has shown mild antibacterial activity against P. aeruginosa in vitro, but the mechanism of potent antimicrobial activity of SH against P. aeruginosa infection in vivo remains unclear. Methods: Here, using the mouse pneumonia model induced by P. aeruginosa nasal drip to explore the therapeutic effects of SH. Results: We found that SH exhibits dose-dependent therapeutic effects of reducing P. aeruginosa burden and systemic inflammation in pneumonia mice. SH ameliorates inflammatory gene expression and production of inflammatory proteins, such as interleukin-6 (IL-6), nuclear factor kappa-B (NF-κB) and toll-like receptor 4 (TLR4), associated with the TLR4/NF-κB pathway in mice with P. aeruginosa pneumonia. Furthermore, we analyzed the intestinal flora of mice and found that compared with the model group, the abundance and diversity of beneficial bacterial flora of SH treatment groups increased significantly, suggesting that SH can improve the intestinal flora disorder caused by inflammation. In addition, SH improves alpha and beta diversity index and reduces species abundance differences of intestinal flora in pneumonia mice. Discussion: Taken together, our presented results indicate that SH may effectively alleviate the acute pulmonary infection induced by P. aeruginosa by reducing the disturbance of regulating immunity and intestinal flora in mice.

[Regulatory effect of Bushenfang on the serum testosterone level of naturally aging rats and its mechanism].

OBJECTIVE: To study the regulatory effect of Bushenfang on the serum testosterone (T) level of naturally aging rats and its mechanism, in order to provide a theoretical and experimental basis for the clinical treatment of late onset hypogonadism (LOH) in males. METHODS: Thirty-two 18-month-old male SD rats were randomly divided into four groups of equal number, naturally aging model and low-, medium- and high-dose Bushenfang groups, and another eight 4-month-old rats were taken as normal controls. The rats of the aging model and normal control groups were treated with normal saline, while those of the low-, medium- and high-dose Bushenfang groups received intragastrically Bushenfang at 3.25, 7.50 and 15.00 g/kg, respectively, all for 3 weeks. Then the rats were sacrificed, the histomorphologic changes of the testis observed by HE staining, the serum T level measured by radioimmunoassay, and the expressions of the StAR protein, P450scc and 3beta-HSD I determined by RT-PCR. RESULTS: The number of Leydig cells was obviously increased after Bushenfang treatment. The levels of serum T were significantly higher in the low-, medium- and high-dose Bushenfang groups ([6.74 +/- 1.56] nmol/L, [8.50 +/- 1.99] nmol/L and [12.41 +/- 2.91] nmol/L) than in the model group ([3.48 +/- 0.75] nmol/L) (P < 0.05). The three Bushenfang groups also showed a remarkable elevation in the mRNA expressions of StAR (0.74 +/- 0.29, 0.83 +/- 0.32 and 1.35 +/- 0.50), P450scc (0.72 +/- 0.36, 1.023 +/- 0.30 and 1.41 +/- 0.37) and 3beta-HSD I (0.58 +/- 0.14, 0.72 +/- 0.07 and 0.85 +/- 0.18), as compared with the models (StAR: 0.44 +/- 0.09; P450scc: 0.33 +/- 0.05; 3beta-HSD I: 0.34 +/- 0.02), with significant differences in the StAR expression between the high-dose Bushenfang and the model groups, as well as in P450scc and 3beta-HSD I expressions between the medium- and high-dose Bushenfang and the model groups (P < 0.05). CONCLUSION: Bushenfang could improve the pathological status of testicular injury and increase the expression of testosterone synthetase, which might be the mechanism behind its regulatory effect on the serum T level of aging rats.

3D bioprinting of a biomimetic meniscal scaffold for application in tissue engineering.

Appropriate biomimetic scaffolds created via 3D bioprinting are promising methods for treating damaged menisci. However, given the unique anatomical structure and complex stress environment of the meniscus, many studies have adopted various techniques to take full advantage of different materials, such as the printing combined with infusion, or electrospining, to chase the biomimetic meniscus, which makes the process complicated to some extent. Some researchers have tried to tackle the challenges only by 3D biopringting, while its alternative materials and models have been constrained. In this study, based on a multilayer biomimetic strategy, we optimized the preparation of meniscus-derived bioink, gelatin methacrylate (GelMA)/meniscal extracellular matrix (MECM), to take printability and cytocompatibility into account together. Subsequently, a customized 3D bioprinting system featuring a dual nozzle + multitemperature printing was used to integrate the advantages of polycaprolactone (PCL) and meniscal fibrocartilage chondrocytes (MFCs)-laden GelMA/MECM bioink to complete the biomimetic meniscal scaffold, which had the best biomimetic features in terms of morphology and components. Furthermore, cell viability, mechanics, biodegradation and tissue formation in vivo were performed to ensure that the scaffold had sufficient feasibility and functionality, thereby providing a reliable basis for its application in tissue engineering.

A region-based lossless watermarking scheme for enhancing security of medical data.

This paper presents a lossless watermarking scheme in the sense that the original image can be exactly recovered from the watermarked one, with the purpose of verifying the integrity and authenticity of medical images. In addition, the scheme has the capability of not introducing any embedding-induced distortion in the region of interest (ROI) of a medical image. Difference expansion of adjacent pixel values is employed to embed several bits. A region of embedding, which is represented by a polygon, is chosen intentionally to prevent introducing embedding distortion in the ROI. Only the vertex information of a polygon is transmitted to the decoder for reconstructing the embedding region, which improves the embedding capacity considerably. The digital signature of the whole image is embedded for verifying the integrity of the image. An identifier presented in electronic patient record (EPR) is embedded for verifying the authenticity by simultaneously processing the watermarked image and the EPR. Combining with fingerprint system, patient's fingerprint information is embedded into several image slices and then extracted for verifying the authenticity.

Lossless watermarking for verifying the integrity of medical images with tamper localization.

Given the ease of alteration of digital data, integrity verification and tamper detection for medical images are becoming ever more important. In this paper, instead of using the conventional irreversible block-based watermarking approach to achieve tamper localization, we propose to incorporate such functionality into the region-based lossless watermarking scheme. This is achieved by partitioning an image into certain non-overlapping regions and appending the associated local authentication information directly into the watermark payload. A region of authentication, which can be flexibly specified by the user, is partitioned into small regions in a multilevel hierarchical manner. Such hierarchical structure allows the user to easily adjust the localization accuracy, and makes the tamper detection efficient. Experimental results demonstrate the effectiveness of tamper localization.

A grid-based model for integration of distributed medical databases.

Grid has emerged recently as an integration infrastructure for sharing and coordinated use of diverse resources in dynamic, distributed environment. In this paper, we present a prototype system for integration of heterogeneous medical databases based on Grid technology, which can provide a uniform access interface and efficient query mechanism to different medical databases. After presenting the architecture of the prototype system that employs corresponding Grid services and middleware technologies, we make an analysis on its basic functional components including OGSA-DAI, metadata model, transaction management, and query processing in detail, which cooperate with each other to enable uniform accessing and seamless integration of the underlying heterogeneous medical databases. Then, we test effectiveness and performance of the system through a query instance, analyze the experiment result, and make a discussion on some issues relating to practical medical applications. Although the prototype system has been carried out and tested in a simulated hospital information environment at present, the underlying principles are applicable to practical applications.

Effect of different ranges of systolic blood pressure on left ventricular structure and diastolic function in a Chinese population: a cross-sectional population-based Shunyi study.

OBJECTIVES: To evaluate the effect of different ranges of systolic blood pressure (SBP) on left ventricular (LV) geometry and diastolic function in Chinese population. DESIGN: Cross-sectional study. SETTING: Peking Union Medical College Hospital in Beijing, China. PARTICIPANTS: All inhabitants aged 35 years or older, living in five villages of Shunyi were invited. Exclusion criteria included individuals who declined participation, presence of moderate to severe valvular heart disease, persistent atrial fibrillation and suboptimal echocardiograms. INTERVENTIONS: The baseline data of 1051 participants were analysed. The relationship between SBP and LV geometric and diastolic function assessed by echocardiography was analysed after adjusting for conventional cardiac risk factors. RESULTS: The adjusted value of SBP was independently associated with LV hypertrophy (LVH) and LV diastolic dysfunction (LVDDF) (all p<0.01). Setting individuals with SBP <120 mm Hg as the reference group (group 1), those with SBP between 120 mm Hg and 140 mm Hg (group 2) had higher risk odds of LVH and those with SBP ≥140 mm Hg (group 3) had higher risk odds of LVH and LVDDF (all p<0.01). With the increase of SBP, LV mass index (LVMI) and E/e' stepwise increased and e' stepwise decreased significantly from group 1 to 3 (all p<0.05). In the whole population, SBP was independently correlated with LVMI, LVEDD, Left Atrial Volume Index, e', and E/e' (all p<0.01). CONCLUSIONS: SBP was independently related to LVH and LVDDF, SBP between 120 and 140 mm Hg was independently related to worse LV remodelling and diastolic function, these findings indicated the potential benefit of intensive SBP control.

[Approaching molecular imaging].

In this paper the concept of molecular imaging is introduced, and its importance is addressed. Besides, the key points of molecular imaging are briefly reviewed from a view of engineering. Particular emphasis is given to the analysis of the function and the position of traditional medical imaging modalities in the era of molecular imaging. Finally a discussion is made for the further development of medical imaging modalities along the line of molecular imaging.

[Identity recognition based on local registration of chest radiography].

In a PACS system, doctors can avoid the mistakes in filing chest radiographs by comparing the new image with the old ones from the same patient. An automatic method with digital image processing technology is introduced in the paper, which is realized by general location of anatomical structures, local image registration and BP artificial neural network, so as to achieve good results for identity recognition.

[Preliminary study on force feedback of acupuncture in virtual reality based on the visible human].

This paper discusses the application of virtual reality technology in the 3-D visible human body and acupuncture research. Based on the 3-D visible human fused with the localization information and hierarchy of acupoints, the paper analyzes the force against the needle and haptic rendering during the needle manipulation according to the physical properties of different tissues. A haptic model is constructed to demonstrate the force behaviors during acupuncture, and the force will be produced and passed to the manipulator by a force feedback device. It enriches the contents of 3-D visible human project, provides a dynamic simulation instrument for acupuncture teaching, and supplies a platform for acupuncture research.

[Development of DICOM software platfrom for medical image communication].

In this paper, we have brought forward the framework design of DICOM software platform, using the SUR-DICOM-Lib software and have completed the connection test with the RSNA-CTNT Test Node. PACS, DICOM, realize

[The study of associated reconstruction using MV linear accelerator and cone-beam CT].

In this paper, we proposed a new scan mode and image reconstruction method, which combines the data from both the linear accelerator and the cone-beam CT to reconstruct the volume with a limited rotation angle and low sampling rate. The classical filtered backprojection method and the iterative method are utilized to reconstruct the volume. The reconstruction results of the two methods are compared with each other with a relavant anlysis given here.

[Research on testing the robustness of DICOM-e-mail secure teleradiology systems].

DICOM-e-mail is a secure teleradiology protocol released by German Radiology Society and has already been applied clinically. To improve the robustness of the system, the protocol has been upgraded by adding some mechanisms such as system feedback. Moreover, a test method is also implemented by sending erroneous mails to application software that supports DICOM-e-mail. Through the tests for two different DICOM-e-mail teleradiology application, the validity of the new protocol is proved and at the same time some bugs are found. The implementation of the latest protocol and the general error tests can help to make the whole teleradiology system a better robustness. The implementation of DICOM-e-mail protocol in our country is also discussed in this paper.

[Research on the distributed PACS based on grid technology].

In this paper, we introduce the grid technology into the design of the distributed PACS. First, we analyse the architecture and functions of OGSA-DAI, and then, introduce a model of the distributed PACS based on OGSA-DAI, and give a detailed analysis on its basic components and workflow. Finally, we make a conclusion on the distributed PACS based on grid technology.

Association of Common Genetic Variants in Mitogen-activated Protein Kinase Kinase Kinase Kinase 4 with Type 2 Diabetes Mellitus in a Chinese Han Population.

BACKGROUND: A study has identified several novel susceptibility variants of the mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) gene for type 2 diabetes mellitus (T2DM) within the German population. Among the variants, five single nucleotide polymorphisms (SNPs) of MAP4K4 (rs1003376, rs11674694, rs2236935, rs2236936, and rs6543087) showed significant association with T2DM or diabetes-related quantitative traits. We aimed to evaluate whether common SNPs in the MAP4K4 gene were associated with T2DM in the Chinese population. METHODS: Five candidate SNPs were genotyped in 996 patients newly diagnosed with T2DM and in 976 control subjects, using the SNPscan™ method. All subjects were recruited from the Second Affiliated Hospital, Harbin Medical University from October 2010 to September 2013. We evaluated the T2DM risk conferred by individual SNPs and haplotypes using logistic analysis, and the association between the five SNPs and metabolic traits in the subgroups. RESULTS: Of the five variants, SNP rs2236935T/C was significantly associated with T2DM in this study population (odds ratio = 1.293; 95% confidence interval: 1.034-1.619, P= 0.025). In addition, among the controls, rs1003376 was significantly associated with an increased body mass index (P = 0.045) and homeostatic model assessment-insulin resistance (P = 0.037). CONCLUSIONS: MAP4K4 gene is associated with T2DM in a Chinese Han population, and MAP4K4 gene variants may contribute to the risk toward the development of T2DM.

Growth and development during early manhood as determinants of prostate size in later life.

BACKGROUND: Age and androgens are key determinants of benign prostate hyperplasia, but the mechanisms remain unclear. We examine the relationship between androgens and total, central, and peripheral prostate volume with a focus on early life factors. METHODS: We conducted a cross-sectional observational study of 406 community-dwelling Australian men aged 20-82 yr old without known prostate disease. Prostate zonal (total, central, and peripheral) volumes were measured by planimetric transrectal ultrasound. Participants completed questionnaires, underwent physical examination, and provided blood samples to measure total, free, and bioavailable testosterone, dihydrotestosterone, estradiol, SHBG, LH, FSH, and prostate-specific antigen. RESULTS: Prostate zonal volumes were positively associated with age, prostate-specific antigen, early onset of puberty, current height, body surface area, lean body mass, hip and waist circumference as well as recalled height and weight during puberty and adolescence but not current weight, fat mass, or body mass index. Stepwise multivariate regression modeling indicated that age and height were the only independent predictors of prostate zonal volumes. When adjusted for age and sampling time of day, the negative correlations of age-adjusted prostate zonal volumes with current blood total, free, and bioavailable testosterone and the positive correlation with blood SHBG were no longer significant. CONCLUSIONS: This study suggests that early and long-term androgen exposure may have long-acting effects on mature prostate zonal volumes, whereas relationships with current blood androgens and related hormones levels were mostly a result of confounding by age. Additional studies on the mechanism of androgen effects on late-life prostate diseases should consider lasting effects of early-life androgen exposure.