Bis-benzylisoquinoline alkaloids inhibit African swine fever virus internalization and replication by impairing late endosomal/lysosomal function.

African swine fever (ASF), caused by the African swine fever virus (ASFV), is a highly infectious disease afflicting domestic pigs and wild boars. It exhibits an alarming acute infection fatality rate of up to 100%. Regrettably, no commercial vaccines or specific drugs for combating this disease are currently available. This study evaluated the anti-ASFV activities in porcine alveolar macrophages, 3D4/21 cells, and PK-15 cells of four bis-benzylisoquinoline alkaloids (BBAs): cepharanthine (CEP), tetrandrine, fangchinoline, and iso-tetrandrine. Furthermore, we demonstrated that CEP, which exhibited the highest selectivity index (SI = 81.31), alkalized late endosomes/lysosomes, hindered ASFV endosomal transport, disrupted virus uncoating signals, and thereby inhibited ASFV internalization. Additionally, CEP disrupted ASFV DNA synthesis, leading to the inhibition of viral replication. Moreover, berbamine was labeled with NBD to synthesize a fluorescent probe to study the cellular location of these BBAs. By co-staining with Lyso-Tracker and lysosome-associated membrane protein 1, we demonstrated that BBAs target the endolysosomal compartments for the first time. Our data together indicated that BBAs are a class of natural products with significant inhibitory effects against ASFV infection. These findings suggest their potential efficacy as agents for the prevention and control of ASF, offering valuable references for the identification of potential drug targets.IMPORTANCEThe urgency and severity of African swine fever (ASF) underscore the critical need for effective interventions against this highly infectious disease, which poses a grave threat to domestic pigs and wild boars. Our study reveals the potent anti-African swine fever virus (ASFV) efficacy of bis-benzylisoquinoline alkaloids (BBAs), particularly evident in the absence of progeny virus production under a 5 µM concentration treatment. The structural similarity among cepharanthine, tetrandrine, fangchinoline, and iso-tetrandrine, coupled with their analogous inhibitory stages and comparable selectivity indexes, strongly suggests a shared antiviral mechanism within this drug category. Further investigation revealed that BBAs localize to lysosomes and inhibit the internalization and replication of ASFV by disrupting the endosomal/lysosomal function. These collective results have profound implications for ASF prevention and control, suggesting the potential of the investigated agents as prophylactic and therapeutic measures. Furthermore, our study offers crucial insights into identifying drug targets and laying the groundwork for innovative interventions.

Bibliometric analysis of traditional Chinese medicine in the treatment of inflammatory bowel disease.

OBJECTIVE: This study conducts a bibliometric analysis of literature on the treatment of inflammatory bowel disease (IBD) with traditional Chinese medicine (TCM) to explore its research status, hotspots, and development trends, providing ideas and references for further research. METHOD: We screened literature for treating IBD with TCM from the Web of Science Core Collection (WOSCC), and used the VOSviewer software (1.6.18) to discover cooperation among countries, institutions, authors, and information on journals, keywords, etc. We use the CiteSpace software (6.2.R2) to analyze co-citation and burst discovery of references. RESULTS: In all, 440 relevant literature papers were searched and screened from the WOSCC database. The results showed that the number of publications concerning treating IBD with TCM has shown a significant growth in the past decade. China is far ahead in terms of article output, occupying a dominant position. The institution with the most published articles is Nanjing University of Traditional Chinese Medicine. The authors who have published most of the articles are Dai Yancheng, Shi Rui, and Zhou Lian. The Journal of Ethnopharmacology published maximum articles in this field, while Gastroenterology was the most cited journal. Ungaro et al.'s article entitled "Ulcerative colitis" (https://doi.org/10.1016/S0140-6736(16)32126-2), published in The Lancet in 2017 was the most cited study. The high-frequency keywords mainly include ulcerative colitis, inflammation, NF-κB, expression, traditional Chinese medicine, gut microbiota, activation, mice, cells, etc. CONCLUSIONS: The research heat for treating IBD with TCM has risen over the past decade, with studies focusing on three main aspects: clinical studies of TCM, basic pharmacology, and animal experimental research. The research hotspot shifted from pathogenesis, clinical study of TCM, basic pharmacology, and complementary therapies to the study of network pharmacology and the mechanism of action of TCM related to gut microbiota. Network pharmacology and gut microbiota are at the frontiers of research and turning to be the future research trends to provide new insights and ideas for further research for treating IBD with TCM.

Role of cspA on the Preparation of Escherichia coli Competent Cells by Calcium Chloride Method.

One of the fundamental techniques in genetic engineering is the creation of Escherichia coli competent cells using the CaCl2 method. However, little is known about the mechanism of E. coli competence formation. We have previously found that the cspA gene may play an indispensable role in the preparation of E. coli DH5α competent cells through multiomics analysis. In the present study, the cellular localization, physicochemical properties, and function of the protein expressed by the cspA gene were analyzed. To investigate the role of the cspA gene in E. coli transformation, cspA-deficient mutant was constructed by red homologous recombination. The growth, transformation efficiency, and cell morphology of the cspA-deficient strain and E. coli were compared. It was found that there were no noticeable differences in growth and morphology between E. coli and the cspA-deficient strain cultured at 37°C, but the mutant exhibited increased transformation efficiencies compared to E. coli DH5α for plasmids pUC19, pET-32a, and p1304, with enhancements of 2.23, 2.24, and 3.46 times, respectively. It was proved that cspA gene is an important negative regulatory gene in the CaCl2 preparation of competent cells.

Discharge coefficient of vertical sluice gates with broad crested weir under free-submerged orifice flows using best subset regression.

Accurate calculation of flow discharge for sluice gates is essential in irrigation, water supply, and structure safety. The measurement of discharge with the requirement of distinguishing flow regimes is not conducive to application. In this study, a novel approach that considers both free and submerged flow was proposed. The energy-momentum method was employed to derive the coefficient of discharge. Subsequently, the discharge coefficient was determined through the experiment which was performed on the physical model of a vertical sluice gate with a broad-crested weir. Feature engineering, incorporating dimensional analysis, feature construction, and correlation-based selection were performed. The best subset regression method was employed to develop regression equations of the discharge coefficient with the generated features. The derived formula was applied to compute the discharge coefficient in the vertical sluice gate and determine the flow discharge. The accuracy of adopted method was assessed by comparing it with recent studies on submerged flow, and the results demonstrate that the developed approach achieves a high level of accuracy in calculating flow discharge. The coefficient of determination for the calculated flow rate is 0.993, and the root mean square percentage error is 5.04%.

[Application Progress of Resting-State Functional Magnetic Resonance Imaging in Study of Default Mode Network in Patients with Vascular Cognitive Impairment].

Vascular cognitive impairment（VCI） is a group of syndromes ranging from mild cognitive impairment to dementia caused by cerebrovascular disease, due to the lack of sensitivity and specific biomarkers, it is difficult to identify and diagnose early. Abnormal connectivity is observed in brain regions of patients with vascular cognitive disorders, locates mainly in the default mode network（DMN）, and changes in their abnormal functional connectivity correlated with the degree of patients' cognitive impairment. Resting-state functional magnetic resonance imaging(rs-fMRI) is a commonly used method to detect the internal activity of the brain at resting state. The use of various rs-fMRI to study abnormal changes in the DMN in patients with VCI is useful to further investigate the pathogenesis of VCI and provide an objective basis for imaging. This article mainly reviews the application of rs-fMRI in the DMN in patients with VCI, bringing new perspectives for the correct diagnosis and assessment of VCI.

Renal clearable polyfluorophore nanosensors for early diagnosis of cancer and allograft rejection.

Optical nanoparticles are promising diagnostic tools; however, their shallow optical imaging depth and slow clearance from the body have impeded their use for in vivo disease detection. To address these limitations, we develop activatable polyfluorophore nanosensors with biomarker-triggered nanoparticle-to-molecule pharmacokinetic conversion and near-infrared fluorogenic turn-on response. Activatable polyfluorophore nanosensors can accumulate at the disease site and react with disease-associated proteases to undergo in situ enzyme-catalysed depolymerization. This disease-specific interaction liberates renal-clearable fluorogenic fragments from activatable polyfluorophore nanosensors for non-invasive longitudinal urinalysis and outperforms the gold standard blood and urine assays, providing a level of sensitivity and specificity comparable to those of invasive biopsy and flow cytometry analysis. In rodent models, activatable polyfluorophore nanosensors enable ultrasensitive detection of tumours (1.6 mm diameter) and early diagnosis of acute liver allograft rejection. We anticipate that our modular nanosensor platform may be applied for early diagnosis of a range of diseases via a simple urine test.

Unnatural tetradeoxy echinocandins produced by gene cluster design and heterologous expression.

The hydroxyl groups in the amino acid residues of echinocandin B were related to the biological activity, the instability, and the drug resistance. The modification of hydroxyl groups was expected to obtain the new lead compounds for next generation of echinocandin drug development. In this work one method for heterologous production of the tetradeoxy echinocandin was achieved. A reconstructed biosynthetic gene cluster for tetradeoxy echinocandins composed of ecdA/I/K and htyE was designed and successfully hetero-expressed in Aspergillus nidulans. The target product of echinocandin E (1) together with one unexpected derivative echinocandin F (2), were isolated from the fermentation culture of engineered strain. Both of compounds were unreported echinocandin derivatives and the structures were identified on the basis of mass and NMR spectral data analysis. Compared with echinocandin B, echinocandin E demonstrated superior stability and comparable antifungal activity.

The impact of metabolic diseases and their comorbidities for stroke in a middle-income area of China: a case-control study.

BACKGROUND: There are few studies on the comorbidity of hypertension (HTN), diabetes mellitus (DM) and dyslipidemia (DLP) associated with stroke. We aimed to explore the relationship between the number of metabolic diseases and stroke and its different subtypes, and to reveal whether metabolic diseases alone or coexist can significantly increase the risk of stroke. METHODS: We completed a multi-center case-control study in Jiangxi Province, China. Neuroimaging examination was done in all cases. Controls were stroke-free adults recruited from the community in the case concentration area and matched with the cases in 1:1 ratio by age and sex. Odds ratios (OR) were calculated by conditional logistic regression. RESULTS: We enrolled 11,729 case-control pairs. The estimated ORs among patients with 1, 2 and 3 metabolic diseases were 3.16 (2.78-3.60), 7.11 (6.16-8.20), 12.22 (9.73-15.36), respectively after adjusting age, body mass index, urban-rural areas, cardiac disease, smoking, alcohol intake, physically active, high intake of salt, meat-biased diet, high homocysteine. The coexistence of HTN and DM (OR: 7.67), the coexistence of HTN and DLP (OR:7.58), and the coexistence of DM and DLP (OR:3.64) can all significantly increase the risk of stroke. HTN alone or combined other metabolic diseases were significantly more strongly associated with intracerebral haemorrhage than ischemic stroke. CONCLUSIONS: The risk of stroke increased with the number of chronic metabolic diseases. It is necessary to regularly monitor blood pressure, blood sugar and blood lipids and strengthen lifestyle management and take appropriate drug interventions to prevent exposure to multiple metabolic diseases based on existing conditions.

High internal phase Pickering emulsions stabilised by ultrasound-induced soy protein-ß-glucan-catechin complex nanoparticles to enhance the stability and bioaccessibility of curcumin.

AIMS: To evaluate the potential applications of soy protein-glucan-catechin (SGC) complexes prepared with different ultrasound times in stabilising high internal phase Pickering emulsion (HIPPE) and delivering curcumin. METHODS: The SGC complexes were characterised by particle size, morphology, zeta potential, Fourier transform infra-red, and fluorescence spectroscopy. Formation and stability of curcumin emulsions were monitored by droplet size, microstructure, rheological property, lipid oxidation, and in vitro digestion. RESULTS: Short-time ultrasound-induced complexes (SGC-U15) exhibited a small size and wettability of ∼82.5°. The chemical stability and bioaccessibility of curcumin was greatly improved by SGC-U15-stabilised HIPPEs, even after 70 days of storage, heating at 100 °C for 30 min, ultraviolet irradiation for 120 min, and in vitro digestion, owing to the formation of elastic gel-like structure at the oil/water interfaces. CONCLUSION: Our findings may contribute to the design of emulsion-based delivery systems using ultrasound-induced protein-polysaccharide-polyphenol complexes.

First report of Botrytis cinerea causing gray mold on Prunella vulgaris in Hubei province, China.

Prunella vulgaris L. is a perennial herb plant of the Lamiaceae family, and its dried spicas have been widely used as medicine, health-promoting food or tea around the world. P. vulgaris is distributed all over the world, such as Europe, Asia, northwestern Africa and North America, as well as the Huaihe River Basin and the middle and lower Yangtze River Basin in China. In February 2022, a serious disease like gray mold occurred in planting fields of P. vulgaris in Wuhan, Hubei (N30°27'07″, E114°15'49″), causing approximately 20% of plants were diseased in the field. Early symptoms were characterized by small, round gray-brown lesions on the leaves of P. vulgaris. Later, a large number of stems and leaves are wilted or necrotic, associated with wet rot and waterlogged spots and covered with light gray or grayish white flocculent mildew layer. To determine the causal agent of disease, 10 plants with the typical symptoms were collected from fields. The stems and leaves of diseased plants were cut into pieces (2 to 3 mm×5 mm), disinfected with 75% ethanol for 3 minutes, rinsed 3 times with sterile water. Each lesion sample was isolated and purified using separate PDA petri dishes at 25°C, and ultimately all samples yielded morphologically consistent pure strain colonies. From the 10 isolates obtained, XKC-1 was chosen as a representative isolate for further study. XKC-1 colonies showed gray aerial mycelia, which were fast-growing and grew over the whole plate (9 cm) after 4 days. In addition, some black and hard sclerotia (1.88±0.94 mm, n=50) with round or irregular shape developed on the colonies after approximately 10 days of incubation at 25°C (Fig. 2A, B). XKC-1 showed branched conidiophores with enlarged apical cells and numerous conidia (Fig. 2C). Unicellular conidia were colorless or gray, ellipsoid or ovoid, smooth and 7.91-12.38 µm × 10.08-13.82 µm (n=30) in size (Fig. 2D). Based on morphological characteristics, the isolate was initially identified as Botrytis sp. (Ellis 1971). To further identify the species, the genomic DNA of XKC-1 was extracted, and the ITS, LSU and G3PDH genes were amplified with the primers ITS1/ITS4, LROR/LR5 (Zhou et al. 2022) and G3PDH-F/G3PDH-R (Jin et al. 2022), respectively. The results indicated that the ITS (ON090404), LSU (ON090417), and G3PDH (ON169893) sequences were 99.80%, 100% and 99.46% identical to the sequences of Botrytis cinerea Pers. strain (MK370693.1, MN148533.1, MN630267.1), respectively. A phylogenetic tree constructed based on a concatenated sequence (ITS, LSU, G3PDH) using the neighbor-joining method in MEGA7 (Tamura et al. 2013) revealed that XKC-1 grouped with concatenated sequences from three representative B. cinerea isolates in GenBank. Based on the morphological characteristics and molecular identification, the strain XKC-1 was identified as Botrytis cinerea. For pathogenicity tests on detached leaves, 5 mm PDA cakes prepared from XKC-1 were placed on the leaves obtained from healthy P. vulgaris after wounding with a needle (n=10), while PDA medium without mycelia were used as control (25 ± 2°C) (Li et al.2020). Mycelia began to germinate and infect plant tissues at 1 dpi. A large part of the leaves showed water soaked spots covered with mycelia on the surface at 4 dpi. For whole plant inoculations, stem bases of five P. vulgaris seedlings were pierced with sterile needle, and then inoculated with three XKC-1 mycelium PDA cakes. Five plants were inoculated with three PDA cakes without mycelia as a control. After 2-4 days, lesions appeared on the leaves and covered with a gray-white mycelial layer, similar to those observed in the field. However, controls remained symptom free. The pathogen was reisolated from the diseased tissues, the colonies, microscopic characteristics and molecular identification were consistent with those of XKC-1. To our knowledge, this is a first report of B. cinerea causing gray mold on P. vulgaris in Hubei, China. This report would provide resources and reference for controlling of the increased incidence and economic losses of gray mold on P. vulgaris.

Insights into the Structures, Inhibitors, and Improvement Strategies of Glucose Oxidase.

Glucose oxidase, which uses molecular oxygen as an electron acceptor to specifically catalyze the conversion of ß-d-glucose to gluconic acid and hydrogen peroxide (H2O2), has been considered an important enzyme in increasing environmental sustainability and food security. However, achieving the high yield, low price and high activity required for commercial viability remains challenging. In this review, we first present a brief introduction, looking at the sources, characteristics, catalytic process, and applications of glucose oxidase. Then, the predictive structures of glucose oxidase from two different sources are comparatively discussed. We summarize the inhibitors of glucose oxidase. Finally, we highlight how the production of glucose oxidase can be improved by optimizing the culture conditions and microbial metabolic engineering.

Targeting peripheral immune organs with self-assembling prodrug nanoparticles ameliorates allogeneic heart transplant rejection.

Organ transplantation has become a mainstay of therapy for patients with end-stage organ diseases. However, long-term administration of immunosuppressive agents, a scheme for improving the survival of transplant recipients, has been compromised by severe side effects and posttransplant complications. Therapeutic delivery targeting immune organs has the potential to address these unmet medical issues. Here, through screening of a small panel of mammalian target of rapamycin complex kinase inhibitor (TORKinib) compounds, a TORKinib PP242 is identified to be able to inhibit T cell function. Further chemical derivatization of PP242 using polyunsaturated fatty acids (i.e., docosahexaenoic acid) transforms this water-insoluble hydrophobic agent into a self-assembling nanoparticle (DHA-PP242 nanoparticle [DPNP]). Surface PEGylation of DPNP with amphiphilic copolymers renders the nanoparticles aqueously soluble for preclinical studies. Systemically administered DPNP shows tropism for macrophages within peripheral immune organs. Furthermore, DPNP regulates differentiation of adoptively transferred T cells in a macrophage-dependent manner in Rag1-/- mouse model. In an experimental model of heart transplantation, DPNP significantly extends the survival of grafts through inducing immune suppression, thus reducing the inflammatory response of the recipients. These findings suggest that targeted delivery of TORKinibs exploiting prodrug-assembled nanoparticle scaffolds may provide a therapeutic option against organ rejection.

Discovery and validation of FBLN1 and ANT3 as potential biomarkers for early detection of cervical cancer.

BACKGROUND: To validate markers for cervical carcinoma (CC) and precancerous lesions related with HPV infections. METHODS: Three different cervical cancer cell lines C-33A, SiHa and Caski were used for secretome profiling by label-free quantitative proteomics. Cervical exfoliated cells and matching serum samples were collected from 284 patients with normal control (n = 75, 26.41 %), precancerous lesions (n = 88, 30.99 %) and early stage cervical squamous carcinoma (n = 121, 42.61 %). HPV subtyping and quantification was performed by PCR and hybridization. 20 candidate proteins identified in previous screening studies (tissue, plasma, cells) were quantified by ELISA. Finally, highly quantitative parallel reaction monitoring mass spectrometry was used to assess the specificities and sensitivities of candidate serum markers. RESULTS: While CC was found to be associated with high-risk HPV subtypes, serum antibodies for high risk HPV were not significantly related to the progression of cervical cancer. Significant differences between patient groups were detected for the four proteins CLU, APOA4, APOE and MLH3, but none would allow clinical application due to insufficient sensitivity and specificity and large variability. Subsequent proteomic secretome analysis of cervical cancer cell lines identified a set of 729 common proteins. Cross referencing this dataset with ELISA measurements revealed six candidate proteins of which two, FBLN1 and ANT3, showed co-occurrence with HPV infection (75.7 % and 85 %, respectively) and had promising diagnostic ability in terms of sensitivity and specificity. After the loss of E6/E7 by using CRISPR/Cas9 gene editing, the content of ANT3 and FBLN1 in KoE6/E7 SiHa were downregulated, which indicated the expression of ANT3 and FBLN1 in cervical cancer may be affected by HPV infection. CONCLUSIONS: FBLN1 and ANT3 might be potential tumor- and HPV-associated serum markers.

Integrated Satellite, Unmanned Aerial Vehicle (UAV) and Ground Inversion of the SPAD of Winter Wheat in the Reviving Stage.

Chlorophyll is the most important component of crop photosynthesis, and the reviving stage is an important period during the rapid growth of winter wheat. Therefore, rapid and precise monitoring of chlorophyll content in winter wheat during the reviving stage is of great significance. The satellite-UAV-ground integrated inversion method is an innovative solution. In this study, the core region of the Yellow River Delta (YRD) is used as a study area. Ground measurements data, UAV multispectral and Sentinel-2A multispectral imagery are used as data sources. First, representative plots in the Hekou District were selected as the core test area, and 140 ground sampling points were selected. Based on the measured SPAD values and UAV multispectral images, UAV-based SPAD inversion models were constructed, and the most accurate model was selected. Second, by comparing satellite and UAV imagery, a reflectance correction for satellite imagery was performed. Finally, based on the UAV-based inversion model and satellite imagery after reflectance correction, the inversion results for SPAD values in multi-scale were obtained. The results showed that green, red, red-edge and near-infrared bands were significantly correlated with SPAD values. The modeling precisions of the best inversion model are R² = 0.926, Root Mean Squared Error (RMSE) = 0.63 and Mean Absolute Error (MAE) = 0.92, and the verification precisions are R² = 0.934, RMSE = 0.78 and MAE = 0.87. The Sentinel-2A imagery after the reflectance correction has a pronounced inversion effect; the SPAD values in the study area were concentrated between 40 and 60, showing an increasing trend from the eastern coast to the southwest and west, with obvious spatial differences. This study synthesizes the advantages of satellite, UAV and ground methods, and the proposed satellite-UAV-ground integrated inversion method has important implications for real-time, rapid and precision SPAD values collected on multiple scales.

Genome-wide survey by ChIP-seq reveals YY1 regulation of lincRNAs in skeletal myogenesis.

Skeletal muscle differentiation is orchestrated by a network of transcription factors, epigenetic regulators, and non-coding RNAs. The transcription factor Yin Yang 1 (YY1) silences multiple target genes in myoblasts (MBs) by recruiting Ezh2 (Enhancer of Zeste Homologue2). To elucidate genome-wide YY1 binding in MBs, we performed chromatin immunoprecipitation (ChIP)-seq and found 1820 specific binding sites in MBs with a large portion residing in intergenic regions. Detailed analysis demonstrated that YY1 acts as an activator for many loci in addition to its known repressor function. No significant co-occupancy was found between YY1 and Ezh2, suggesting an additional Ezh2-independent function for YY1 in MBs. Further analysis of intergenic binding sites showed that YY1 potentially regulates dozens of large intergenic non-coding RNAs (lincRNAs), whose function in myogenesis is underexplored. We characterized a novel muscle-associated lincRNA (Yam-1) that is positively regulated by YY1. Yam-1 is downregulated upon differentiation and acts as an inhibitor of myogenesis. We demonstrated that Yam-1 functions through in cis regulation of miR-715, which in turn targets Wnt7b. Our findings not only provide the first genome-wide picture of YY1 association in muscle cells, but also uncover the functional role of lincRNA Yam-1.

Production and in vitro evaluation of a lamotrigine extended release tablet based on a controlled-porosity osmotic pump system.

Osmotic pump delivery systems have made significant advances in the past decades for controlled drug release over a long period of time. Usually, osmotic pump products require sophisticated and expensive laser drill technology resulting in increase in production cost and decrease in production efficiency. In this study, a lamotrigine extended release tablet based on a controlled-porosity osmotic pump (CPOP) system was developed to circumvent laser drill technology in reference, Lamictal XR®. The tablet core was coated by a polymer blend of Acryl-EZE® and HPMC E5. Lactose and HPMC were added in the CPOP core to adjust the release profile. An orthogonal design was employed to optimize the formulation from factors, i.e., core composition, coating materials ratio and coating levels. Comparisons of in vitro drug release profiles were also conducted. The optimized formulation showed a satisfactory zero-order release profile (R2 = 0.9912). Similarity factor, f2 of 77 was obtained in larger scale. The lamotrigine extended release tablets based on the CPOP system showed ideal reproducibility and stability. The developed system has the ability to be an alternative production method for Lamictal XR®, which could circumvent the laser drill technology and promote the osmotic pump generalization.

[Health knowledge awareness in Guangzhou adult residents based on latent profile model].

OBJECTIVE: To explore the application of latent profile model in classification of health knowledge awareness in Guangzhou residents, and identify the characteristics of the heterogeneous population from multi dimensions. METHODS: By stratified cluster sampling, health knowledge and health behavior among 1179 residents in Guangzhou City were investigated. Latent profile model was used to population classification based on health knowledge scores, and compared with traditional clustering method, the demographic and health behaviors with different levels of health knowledge were analyzed. RESULTS: Community residents were divided into three classes of health knowledge awareness model crowd by latent profile model, which accounted for 62. 2%, 27. 4% and 10. 4%, respectively, was superior to the traditional cluster method. Therewere significant differences in the demographic characteristics of different health knowledge subgroups, people who is younger, low education, manual worker with weak health knowledge. And the result showed that the higher level of health knowledge awareness with the better health behavior. CONCLUSION: The application of latent profile model is extended to the field of health education. It can identify the heterogeneous subgroups of different health knowledge awareness effectively, which can indicate the key of health education programmes.

Effect of sports bra type and gait speed on breast discomfort, bra discomfort and perceived breast movement in Chinese women.

This study investigated the effect of sports bra type (encapsulation versus compression) and gait speed on perceptions of breast discomfort, bra discomfort and breast movement reported by Chinese women. Visual analogue scales were used to evaluate breast discomfort, bra component discomfort and perceived breast movement of 21 Chinese participants when they wore an encapsulation or a compression sports bra, while static and while exercising at three different gait speeds. Participants perceived less breast discomfort and breast movement when wearing a compression bra compared to an encapsulation bra at a high gait speed, suggesting that compression bras are likely to provide the most effective support for Chinese women. However, significantly higher bra discomfort was perceived in the compression bra compared to the encapsulation bra when static and at the lower gait speed, implying that ways to modify the design of sports bras, particularly the straps, should be investigated to provide adequate and comfortable breast support. PRACTITIONER SUMMARY: The compression sports bra provided more comfortable support than the encapsulation sports bra for these Chinese women when running on a treadmill. However, these women perceived higher bra discomfort when wearing the compression bra when stationary. Further research is needed to modify the design of sports bras, particularly the straps, to provide adequate and comfortable breast support.

Stimulation of somatic cell reprogramming by ERas-Akt-FoxO1 signaling axis.

Reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) shares much similarity to the cancer initiation process, and the molecular mechanisms underlying both processes remain to be elucidated. Here, we report that a tumor- or embryonic stem cell-specific Ras gene ERas, which encodes a constitutively active form of GTPase, and its downstream Phosphoinositide-3 kinase/Akt signaling pathway are important facilitators for the somatic reprogramming process. We found that overexpression of ERas retrovirally enhanced mouse iPSC induction while ERas knockdown repressed it. Modulation of Akt signaling by genetic or chemical means greatly impacted the reprogramming efficiency. Forced expression of a constitutively active Akt1 gene could rescue the reduced efficiency resulting from ERas knockdown, and point-mutation analyses further revealed that ERas is tightly coupled with Akt signaling to enhance reprogramming. Mechanistically, the forkhead transcription factor FoxO1 can function as a barrier to the iPSC induction, and the inactivation of FoxO1 by Akt-dependent phosphorylation largely accounts for the enhancing effect of ERas-Akt signaling on reprogramming. Collectively, these results unravel the significance of the ERas-Akt-FoxO1 signaling axis in iPSC generation, suggesting a possibly shared molecular basis for both somatic reprogramming and cancer initiation.

Advances in Ubiquitination and Proteostasis in Retinal Degeneration.

Retinal degeneration (RD) is a group of chronic blinding diseases characterised by progressive retinal cell death. As the disease progresses, vision deteriorates due to retinal cell death and impaired retinal integrity, eventually leading to complete loss of vision. Therefore, the function and environmental homeostasis of the retina have an important impact on the pathogenesis and treatment of RD. Ubiquitination, as a complex post-translational modification process, plays an essential role in maintaining retinal homeostasis and normal function. It covalently combines ubiquitin with protein through a series of enzyme-mediated reactions, and participates in cell processes such as gene transcription, cell cycle process, DNA repair, apoptosis and immune response. At the same time, it plays a central role in protein degradation. There are two major protein degradation systems in eukaryotic cells: the ubiquitin-proteasome system and the autophagy-lysosomal system. The protein degradation pathway maintains retinal protein homeostasis by reducing abnormal protein accumulation in the retina through two modes of degradation. Either dysregulation of ubiquitination or disruption of protein homeostasis may lead to the development of RD. This article aims to comprehensively review recent research progress on ubiquitin-related genes, proteins and protein homeostasis in the pathogenesis of RD, and to summarize the potential targeted therapy strategies for it. The review is expected to provide valuable guidance for further development and application of ubiquitination in RD.