ReProMSig: an integrative platform for development and application of reproducible multivariable models for cancer prognosis supporting guideline-based transparent reporting.

Adequate reporting is essential for evaluating the performance and clinical utility of a prognostic prediction model. Previous studies indicated a prevalence of incomplete or suboptimal reporting in translational and clinical studies involving development of multivariable prediction models for prognosis, which limited the potential applications of these models. While reporting templates introduced by the established guidelines provide an invaluable framework for reporting prognostic studies uniformly, there is a widespread lack of qualified adherence, which may be due to miscellaneous challenges in manual reporting of extensive model details, especially in the era of precision medicine. Here, we present ReProMSig (Reproducible Prognosis Molecular Signature), a web-based integrative platform providing the analysis framework for development, validation and application of a multivariable prediction model for cancer prognosis, using clinicopathological features and/or molecular profiles. ReProMSig platform supports transparent reporting by presenting both methodology details and analysis results in a strictly structured reporting file, following the guideline checklist with minimal manual input needed. The generated reporting file can be published together with a developed prediction model, to allow thorough interrogation and external validation, as well as online application for prospective cases. We demonstrated the utilities of ReProMSig by development of prognostic molecular signatures for stage II and III colorectal cancer respectively, in comparison with a published signature reproduced by ReProMSig. Together, ReProMSig provides an integrated framework for development, evaluation and application of prognostic/predictive biomarkers for cancer in a more transparent and reproducible way, which would be a useful resource for health care professionals and biomedical researchers.

Dual roles of ß-arrestin 1 in mediating cell metabolism and proliferation in gastric cancer.

ß-Arrestin 1 (ARRB1) has been recognized as a multifunctional adaptor protein in the last decade, beyond its original role in desensitizing G protein-coupled receptor signaling. Here, we identify that ARRB1 plays essential roles in mediating gastric cancer (GC) cell metabolism and proliferation, by combining cohort analysis and functional investigation using patient-derived preclinical models. Overexpression of ARRB1 was associated with poor outcome of GC patients and knockdown of ARRB1 impaired cell proliferation both ex vivo and in vivo. Intriguingly, ARRB1 depicted diverse subcellular localizations during a passage of organoid cultures (7 d) to exert dual functions. Further analysis revealed that nuclear ARRB1 binds with transcription factor E2F1 triggering up-regulation of proliferative genes, while cytoplasmic ARRB1 modulates metabolic flux by binding with the pyruvate kinase M2 isoform (PKM2) and hindering PKM2 tetramerization, which reduces pyruvate kinase activity and leads to cellular metabolism shifts from oxidative phosphorylation to aerobic glycolysis. As ARRB1 localization was shown mostly in the cytoplasm in human GC samples, therapeutic potential of the ARRB1-PKM2 axis was tested, and we found tumor proliferation could be attenuated by the PKM2 activator DASA-58, especially in ARRB1high organoids. Together, the data in our study highlight a spatiotemporally dependent role of ARRB1 in mediating GC cell metabolism and proliferation and implies reactivating PKM2 may be a promising therapeutic strategy in a subset of GC patients.

M2 macrophages regulate KDM6B/PFKFB2 metabolic reprogramming of cervical squamous cell carcinoma through CXCL1.

Macrophages in the tumor microenvironment can polarize into M1 or M2 forms, with M2 macrophages (M2φ) promoting tumor growth and metastasis in cervical squamous cell carcinoma (CESC). This study explored the effects of M2φ on CESC metabolic reprogramming both in vitro and in vivo. Results showed that M2φ secreted CXCL1, which significantly increased CESC migration and metabolic regulation. Further experiments revealed that CXCL1 upregulated KDM6B to enhance PFKFB2 transcriptional activity, thus regulating CESC glucose metabolism. Transcriptome sequencing screened 5 upregulated genes related to glycolysis, with PFKFB2 showing the most significant increase in cells treated with rCXCL1. Dual-luciferase reporter assay confirmed that rCXCL1 enhances PFKFB2 transcriptional activity. Bioinformatics analysis revealed a high correlation between expressions of KDM6B and PFKFB2 in CESC. Mechanistic experiments demonstrated that KDM6B inhibited H3K27me3 modification to activate PFKFB2 transcriptional expression. In conclusion, M2φ secreted CXCL1 to promote CESC cell migration and invasion, and CXCL1 activated KDM6B expression in CESC cells, inhibiting H3K27 protein methylation modification, and enhanced PFKFB2 transcriptional activity to regulate CESC glucose metabolism. These results provided new insights into the complex interplay between the immune system and cancer metabolism, which may have broader implications for understanding and treating other types of cancer.

In-Depth Comparison of Matrigel Dissolving Methods on Proteomic Profiling of Organoids.

Patient-derived organoids recently emerged as promising ex vivo 3D culture models recapitulating histological and molecular characteristics of original tissues, thus proteomic profiling of organoids could be valuable for function investigation and clinical translation. However, organoids are usually cultured in murine Matrigel (served as scaffolds and matrix), which brings an issue to separate organoids from Matrigel. Because of the complex compositions of Matrigel and thousands of identical peptides shared between Matrigel and organoids, insufficiently dissolved Matrigel could influence proteomic analysis of organoids in multiple ways. Thus, how to dissolve Matrigel matrix and recovery organoid cells efficiently is vital for sample preparation. Here, we comprehensively compared three popular Matrigel dissolving methods (cell recovery solution, dispase, and PBS-EDTA buffer) and investigated the effect of undissolved Matrigel proteins on proteomic profiles of organoids. By integrative analysis of label-free proteomes of Matrigel and stable isotope labeling by amino acids in cell culture proteomes of organoids collected by three methods, respectively, we found that dispase showed an optimal efficiency, with the highest peptide yield and the highest incorporation ratio of stable isotope labeling by amino acids in cell culture labels (97.1%), as well as with the least potential Matrigel contaminants. To help analysis of proteomic profiles of organoids collected by the other two methods, we identified 312 high-confidence Matrigel contaminants, which could be filtered out to attenuate Matrigel interference with minimal loss of biological information. Together, our study identifies bioinformatics and experimental approaches to eliminate interference of Matrigel contaminants efficiently, which will be valuable for basic and translational proteomic research using organoid models.

A Novel PMVK Variant Associated with Familial Porokeratosis.

BACKGROUND: Porokeratosis is a rare chronic progressive hypokeratotic skin disease, possibly related to the mevalonate pathway. Variations in four enzymes, including phosphomevalonate kinase (PMVK) may alter this pathway, ultimately leading to porokeratosis. OBJECTIVES: The aim of the study was to identify the causative gene variant of porokeratosis in a Chinese family and investigate its population frequency and pathogenicity. METHOD: In this study, Sanger sequencing was used to identify the gene variant causative of porokeratosis; its population frequency was investigated by polymerase chain reaction-restriction fragment length polymorphism in 4 patients and three normal individuals as well as in 100 normal unrelated controls; finally, the pathogenicity of the mutation and the associated structural changes were predicted. RESULTS: We identified a novel heterozygous missense variant, c.207G>T (p. Lys69Asn) in the PMVK gene. This variant was found in all patients but not in the normal individuals in this family or in the 100 controls. In silico analysis indicated that the variant was pathogenic; p.Lys69Asn changed the length of the α-helix and the hydrogen bond pattern compared with the wild-type protein. CONCLUSIONS: The novel variant c.207G>T (p. Lys69Asn) in the PMVK gene was the causative variant in this porokeratosis family. This finding provides further evidence for the genetic basis of this disease.

Prediction of outcomes after chemoradiotherapy for cervical cancer by neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio.

BACKGROUND: Cervical cancer ranks as the second most fatal tumour globally among females. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been widely applied to the diagnosis of cancers. METHODS: The clinicopathologic data of 180 patients with stage IB2-IIB cervical cancer who underwent radical concurrent chemoradiotherapy from January 2018 to December 2019 were retrospectively analysed. Receiver operating characteristic (ROC) curves were plotted to analyse the optimal cut-off values of NLR and PLR for predicting the therapeutic effects of concurrent chemoradiotherapy. The associations of PLR and other clinicopathological factors with 1-year survival rates were explored through univariate analysis and multivariate Cox regression analysis, respectively. RESULTS: NLR was significantly associated with the therapeutic effects of neoadjuvant therapy, with the optimal cut-off value of 2.89, area under the ROC curve (AUC) of 0.848 (95% confidence interval [CI]: 0.712-0.896), sensitivity of 0.892 (95% CI: 0.856-0.923) and specificity of 0.564 (95% CI: 0.512-0.592). PLR had a significant association with the therapeutic effects of neoadjuvant therapy, with the optimal cut-off value of 134.27, AUC of 0.766 (95% CI: 0.724-0.861), sensitivity of 0.874 (95% CI: 0.843-0.905) and specificity of 0.534 (95% CI: 0.512-0.556). Lymphatic metastasis ([95% CI: 1.435-5.461], [95% CI: 1.336-4.281], depth of invasion ([95% CI: 1.281-3.546], [95% CI: 1.183-3.359]) and tumour size ([95% CI: 1.129-3.451], [95% CI: 1.129-3.451]) were independent factors influencing the overall survival and disease-free survival (DFS) of patients with cervical cancer. NLR (95%CI: 1.256-4.039) and PLR (95%CI:1.281-3.546) were also independent factors affecting DFS. CONCLUSION: NLR and PLR in the peripheral blood before treatment may predict DFS of patients with stage IB2-IIB cervical cancer.

The clinicopathologic data of 180 patients with stage IB2-IIB cervical cancer who underwent radical concurrent chemoradiotherapy were retrospectively analysed. Receiver operating characteristic curves showed that neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were significantly associated with the therapeutic effects of neoadjuvant therapy. Univariate and multivariate regression analysis revealed that lymphatic metastasis, depth of invasion and tumour size were independent factors influencing the overall survival and disease-free survival (DFS) of patients with cervical cancer. NLR and PLR in the peripheral blood before treatment may predict the DFS of patients with stage IB2-IIB cervical cancer.

The hub genes and their potential regulatory mechanisms in chronic spontaneous urticaria revealed by integrated transcriptional expression analysis.

Chronic spontaneous urticaria (CSU) is a recurrent disease characterized by wheals and or angioedema, and its pathogenesis is still unclear. The microarray datasets of skin tissue from CSU patients and healthy controls were integrated and analysed in Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified using the NetworkAnalyst tool. Then, the Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Subsequently, a protein-protein interaction (PPI) network of DEGs was constructed by STRING and the related hub genes were identified through the MOCDE tool. The potential miRNAs targeting hub genes were predicted based on the intersection of three online databases, namely TargetScanHuman, TargetBase and miRNet. Differentially expressed lncRNAs (DElncRNAs) was performed using the GEO2R tool. The potential miRNAs targeting DElncRNAs were predicted through miRNet. Finally, the shared miRNAs targeting both hub genes and DElncRNAs were used to construct an mRNA/miRNA/lncRNA regulatory network. A total of 296 DEGs were obtained, which were mainly enriched in inflammatory and immune responses. Further, 14 hub genes were identified by the PPI network of DEGs. Clinical correlation analysis showed that the mRNA expressions of S100A7, S100A8, S100A9, S100A12, IL6 and SOCS3 in CSU were positively correlated with the 7-day urticaria activity score (UAS7), and their potential diagnostic value was supported by the receiver operating characteristic curve (ROC) analysis. Five up-regulated lncRNAs in the cytoplasm were obtained by DElncRNAs analysis. The ROC analysis showed that PVT1, SNHG3 and ZBTB20 - AS1 was of potential diagnostic value for CSU. Eight shared miRNAs targeting both hub genes and DElncRNAs were identified and used to construct a competing endogenous RNA (ceRNA) network. It was found that the IL-6/miR - 149 - 5p/ZBTB20 - AS1 axis might play an important role in the activation of mast cells in CSU. IL-6 and its related regulatory molecules may be used as potential diagnostic markers and therapeutic targets for CSU.

Saxagliptin reduces the injury of Alzheimer's disease cell model by down-regulating the expression of miR-483-5p.

This study aimed to investigate the effect of saxagliptin on the injury of Alzheimer's disease (AD) cell model and its possible mechanism. SK-N-SH cells were cultured in vitro and divided into CON group, AD group, AD+L-SAX group, AD+M-SAX group, AD+H-SAX group, AD+anti-miR-NC group, AD+anti-miR-483-5p group, AD+SAX+miR-NC group and AD+SAX+miR-483-5p group. Then the levels of MDA, SOD and GSH-Px in each group were detected by ELISA method; cell apoptosis was detected by flow cytometry; the protein expression levels of Bax and Bcl-2 were detected by Western Blot; the expression level of miR-483-5p was detected by RT-qPCR. Compared with the control group, MDA content, apoptosis rate, and the expression of Bax protein and miR-483-5p increased in the AD group (P<0.05), while the activity of SOD and GSH-Px and the expression of Bcl-2 protein decreased (P<0.05). Compared with the AD group, MDA content, apoptosis rate, and the expression of Bax protein and miR-483-5p decreased in the AD+L-SAX group, AD+M-SAX group and AD+H-SAX group (P<0.05), while the activity of SOD and GSH-Px and the expression of Bcl-2 protein increased (P<0.05). Compared with AD+anti-miR-NC group, MDA content, apoptosis rate, and the expression of Bax protein and miR-483-5p decreased in the AD+anti-miR-483-5p group (P<0.05), while the activity of SOD and GSH-Px and the expression of Bcl-2 protein increased (P<0.05). Compared with AD+SAX+miR-NC group, MDA content, apoptosis rate, and the expression of Bax protein and miR-483-5p increased in the AD+SAX+miR-483-5p group (P<0.05), while the activity of SOD and GSH-Px and the expression of Bcl-2 protein decreased (P<0.05). Saxagliptin may reduce the injury of Alzheimer's disease cell model by down-regulating the expression of miR-483-5p.

Efficacy evaluation of direct antiviral drugs against hepatitis B virus in improving the degree of liver fibrosis.

Introduction: The aim of the study was to find an ideal index reflecting inflammation and fibrosis for patients after antiviral treatment, and compare it with imaging examination (liver stiffness measurement - LSM) and traditional liver fibrosis models (APRI and FIB-4). Material and methods: A total of 77 chronic hepatitis B (CHB) patients who achieved a sustained virological response (SVR) after entecavir (ETV) treatment were included, and the changes of various clinical indicators before and after treatment were compared. Results: After 78 weeks of ETV treatment, WBC and PLT of 77 patients were significantly increased, while ALT, AST and total bilirubin were significantly decreased (p < 0.05). There was no significant difference in serum creatinine (Cr) or blood urea nitrogen (BUN) compared to the values before treatment (p > 0.05). The three non-invasive liver fibrosis indexes, namely, LSM, APRI and FIB-4, were significantly decreased in 77 patients compared to the values before treatment (p < 0.001). Conclusions: Acoustic radiation force impulse (ARFI), fibrosis-4 (FIB-4), aspartate aminotransferase-to-platelet ratio index (APRI) have a high consistency with the grading of liver fibrosis, and can be used to evaluate the severity of liver fibrosis. Among them, ARFI has good diagnostic value for the classification of different degrees of liver fibrosis and the best diagnostic accuracy.

A young patient with heart failure was diagnosed with extra-adrenal paraganglioma: a case report.

BACKGROUND: We present a case of pelvic paraganglioma that presented with heart failure as the primary symptom. CASE PRESENTATION: A 35-year-old man was admitted to hospital due to heart failure. Contrast-enhanced pelvic CT showed mass shadows in the posterior wall of the bladder and multiple enlarged lymph nodes in the retroperitoneal area. Ultrasound-guided puncture was performed, and the pathologic diagnosis was extra-adrenal paraganglioma. The patient refused any chemotherapy and died within six months of diagnosis. CONCLUSION: The possibility of neuroendocrine-related tumors, for example paragangliomas, should be considered in young patients with heart failure, especially those with concomitant hypertension and diabetes.

Design, synthesis and biological evaluation of dehydroabietic acid derivative as potent vasodilatory agents.

Using dehydroabietic acid as the lead compound for structural modification, 25 dehydroabietic acid derivatives were synthesized. Among them, compound D1 not only showed the strongest relaxation effect on the aortic vascular ring in vitro (Emax = 99.5 ± 2.1%, EC50 = 3.03 ± 0.96 µM), but also significantly reduced systolic and diastolic blood pressure in rats at a dose of 2.0 mg/kg in vivo. Next, the vascular protective effect of the best active D1 and its molecular mechanism were further investigated by HUVECs. The results showed that D1 induced endothelium-dependent diastole in the rat thoracic aorta in a concentration-dependent manner. Endothelium removal or aortic ring pretreatment with NG-nitro-l-arginine methylester (l-NAME), 1H-[1,2,4]-oxadiazolo-[4,3-a]-quinoxalin-1-one (ODQ), and tetraethylammonium (TEA) significantly inhibited D1-induced relaxation. In addition, wortmannin, KT5823, triciribine, diltiazem, BaCl2, 4-aminopyridine, indomethacin, propranolol, and atropine attenuated D1-induced vasorelaxation. D1 increased the phosphorylation of eNOS in HUVECs Furthermore, D1 attenuated the expression of TNF-α-induced cell adhesion molecules such as ICAM-1 and VCAM-1. However, this effect was attenuated by the eNOS inhibitors l-NAME and asymmetric dimethylarginine (ADMA). The findings suggest that D1-induced vasorelaxation through the PI3K/Akt/eNOS/NO/cGMP/PKG pathway by activating the KCa, Kir and KV channels or muscarinic and ß-adrenergic receptors, and inhibiting the l-type Ca2+ channels, which is closely related to the hypotensive action of the agent. Furthermore, D1 exhibits an inhibitory effect on vascular inflammation, which is associated with the observed vascular protective effects.

A novel variation in RANBP2 associated with infection-triggered familial acute necrotizing encephalopathy.

Acute necrotizing encephalopathy (ANE) is a rapidly progressive encephalopathy occurring in otherwise healthy children after common viral infections. The condition presents as a spectrum of symptoms ranging from infections to seizures and coma, with the potential to cause long-term neurocognitive impairment or death. Familial and recurrent ANE is referred to as ANE1. A four-generation Chinese family with ANE1 was recruited for genetic analysis. A novel missense variation, c.9041A > G, p.(Glu3014Gly) in RANBP2 was identified in this family. This study is the first to identify a novel variation in RANBP2 in a Chinese family with ANE1.

A novel variant in the ROR2 gene underlying brachydactyly type B: a case report.

BACKGROUND: Brachydactyly type B is an autosomal dominant disorder that is characterized by hypoplasia of the distal phalanges and nails and can be divided into brachydactyly type B1 (BDB1) and brachydactyly type B2 (BDB2). BDB1 is the most severe form of brachydactyly and is caused by truncating variants in the receptor tyrosine kinase-like orphan receptor 2 (ROR2) gene. CASE PRESENTATION: Here, we report a five-generation Chinese family with brachydactyly with or without syndactyly. The proband and her mother underwent digital separation in syndactyly, and the genetic analyses of the proband and her parents were provided. The novel heterozygous frameshift variant c.1320dupG, p.(Arg441Alafs*18) in the ROR2 gene was identified in the affected individuals by whole-exome sequencing and Sanger sequencing. The c.1320dupG variant in ROR2 is predicted to produce a truncated protein that lacks tyrosine kinase and serine/threonine- and proline-rich structures and remarkably alters the tertiary structures of the mutant ROR2 protein. CONCLUSION: The c.1320dupG, p.(Arg441Alafs*18) variant in the ROR2 gene has not been reported in any databases thus far and therefore is novel. Our study extends the gene variant spectrum of brachydactyly and may provide information for the genetic counselling of family members.

Acupuncture Attenuates Ototoxicity Induced by Gentamicin in Mice.

CONTEXT: Presbycusis is age-related, progressive, and symmetrical hearing loss in both ears. Acupuncture can play a vital role in the diagnosis and treatment of deafness, but its functional mechanism is still not entirely clear. OBJECTIVE: The study intended to explore acupuncture's protective effects and mechanism of treatment in addressing ototoxicity induced by gentamicin (GM) in aged mice. DESIGN: The research team designed an animal study, and a mouse model of ototoxicity induced by GM was established. SETTING: The study took place in Nanchong Central Hospital, Sichuan, China. ANIMALS: The animals were 48 male, Kunming mice, with sixteen being three months old and 32 being 18 month old. INTERVENTION: The three-month-old mice were randomly assigned to a control group (n = 8) and a GM group (n = 8). The 18-month-old mice were randomly divided into four groups with eight mice each: a positive control group; a negative control group, the GM group; and two intervention groups, the acupuncture + GM group and the drug + GM group. The GM groups were intraperitoneally injected with 100 mg/kg daily of GM for 10 consecutive days. The acupuncture + GM group received acupuncture, and the drug + GM group was injected intraperitoneally with Genadol. OUTCOME MEASURES: The effects of GM induction and treatment with acupuncture or a drug on the numbers of auditory cochlear hair cells were evaluated via an auditory test and cell staining. A real-time polymerase chain reaction (PCR) was performed for gene detection. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) were measured. RESULTS: The aged mice were susceptible to GM ototoxicity. After acupuncture, the threshold of the auditory brainstem response and the number of cochlear hair cells increased significantly. Acupuncture inhibited oxidative stress via the nuclear factor erythroid-derived factor 2-related factor 2 (NRF2) signaling pathway in the mice. CONCLUSIONS: The data demonstrated that acupuncture can alleviate GM ototoxicity via the NRF2 signaling pathway, providing important support for acupuncture in treatment of GM ototoxicity.

A Novel Method of Aircraft Detection under Complex Background Based on Circular Intensity Filter and Rotation Invariant Feature.

Aircraft detection in remote sensing images (RSIs) has drawn widespread attention in recent years, which has been widely used in the military and civilian fields. While the complex background, variations of aircraft pose and size bring great difficulties to the effective detection. In this paper, we propose a novel aircraft target detection scheme based on small training samples. The scheme is coarse-to-fine, which consists of two main stages: region proposal and target identification. First, in the region proposal stage, a circular intensity filter, which is designed based on the characteristics of the aircraft target, can quickly locate the centers of multi-scale suspicious aircraft targets in the RSIs pyramid. Then the target regions can be extracted by adding bounding boxes. This step can get high-quality but few candidate regions. Second, in the stage of target identification, we proposed a novel rotation-invariant feature, which combines rotation-invariant histogram of oriented gradient and vector of locally aggregated descriptors (VLAD). The feature can characterize the aircraft target well by avoiding the impact of its rotation and can be effectively used to remove false alarms. Experiments are conducted on Remote Sensing Object Detection (RSOD) dataset to compare the proposed method with other advanced methods. The results show that the proposed method can quickly and accurately detect aircraft targets in RSIs and achieve a better performance.

A Novel Fuzzy Controller for Visible-Light Camera Using RBF-ANN: Enhanced Positioning and Autofocusing.

To obtain high-precision for focal length fitting and improve the visible-light camera autofocusing speed, simultaneously, the backlash caused by gear gaps is eliminated. We propose an improved RBF (Radical Basis Function) adaptive neural network (ANN) FUZZY PID (Proportional Integral Derivative) position closed-loop control algorithm to achieve the precise positioning of zoom and focus lens groups. Thus, the Levenberg-Marquardt iterative algorithm is used to fit the focal length, and the improved area search algorithm is applied to achieve autofocusing and eliminate backlash. In this paper, we initially adopt an improved RBF ANN fuzzy PID control algorithm in the position closed-loop in the visible-light camera position and velocity double closed-loop control system. Second, a similar triangle method is used to calibrate the focal length of the visible-light camera system, and the Levenberg-Marquardt iterative algorithm is used to fit the relation of the zoom potentiometer code values and the focal length to achieve the zoom position closed-loop control. Finally, the improved area search algorithm is used to achieve fast autofocusing and acquire clear images. The experimental results show that the ITAE (integrated time and absolute error) performance index of the improved RBF ANN fuzzy PID control algorithm is improved by more than two orders of magnitude as compared with the traditional fuzzy PID control algorithm, and the settling time is 6.4 s faster than that of the traditional fuzzy PID control. Then, the Levenberg-Marquardt iterative algorithm has a fast convergence speed, and the fitting precision is high. The quintic polynomial fitting results are basically consistent with the sixth-degree polynomial. The fitting accuracy is much better than that of the quadratic polynomial and exponential. Autofocusing requires less than 2 s and is improved by more than double that of the traditional method. The improved area search algorithm can quickly obtain clear images and solve the backlash problem.

Recent Advancements in Natural Plant Colorants Used for Hair Dye Applications: A Review.

There is an on-going demand in recent years for safer and "greener" hair coloring agents with the global consumer awareness of the adverse effects of synthetic hair dyes. The belief in sustainability and health benefits has focused the attention of the scientific community towards natural colorants that serve to replace their synthetic toxic counterparts. This review article encompasses the historical applications of a vast array of natural plant hair dyes and summarizes the possible coloration mechanisms (direct dyeing and mordant dyeing). Current information on phytochemicals (quinones, tannins, flavonoids, indigo, curcuminoids and carotenoids) used for hair dyeing are summarized, including their botanical sources, color chemistry and biological/toxicological activities. A particular focus is given on research into new natural hair dye sources along with eco-friendly, robust and cost-effective technologies for their processing and applications, such as the synthetic biology approach for colorant production, encapsulation techniques for stabilization and the development of inorganic nanocarriers. In addition, innovative in vitro approaches for the toxicological assessments of natural hair dye cosmetics are highlighted.

Direct generation of relativistic isolated attosecond pulses in transmission from laser-driven plasmas.

Isolated attosecond pulses are useful to perform pump-probe experiments at a high temporal resolution, and provide a new tool for ultrafast metrology. However, it is still a challenging task to generate such pulses of high intensity, even for a few-cycle laser. Through particle-in-cell simulations, we show that it is possible to directly generate a giant isolated attosecond pulse in the transmission direction from relativistic laser-driven plasmas. Compared to attosecond pulse generation in the reflection direction, no further spectral filtering is needed. The underlying radiation mechanism is coherent synchrotron emission, and the transmitted isolated attosecond pulse can reach relativistic intensity. This provides a promising alternative to generate intense isolated attosecond pulses for ultrafast studies.

CircRNAs and LncRNAs in Osteoporosis.

Osteoporosis is a systemic bone disease with bone fragility and increased fracture risk. The non-coding RNAs (ncRNAs) have appeared as important regulators of cellular signaling and pertinent human diseases. Studies have demonstrated that circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) are involved in the progression of osteoporosis through a variety of pathways, and are considered as targets for the prophylaxis and treatment of osteoporosis. Based on an in-depth understanding of their roles and mechanisms in osteoporosis, we summarize the functions and molecular mechanisms of circRNAs and lncRNAs involved in the progression of osteoporosis and provide some new insights for the prognosis, diagnosis and treatment of osteoporosis.

AQP8 participates in oestrogen-mediated buffalo follicular development by regulating apoptosis of granulosa cells.

Aquaporins (AQPs), a family of small membrane-spanning proteins, are involved in fluid transport, cell signalling and reproduction. Regulating AQP8 expression influences apoptosis of granulosa cells (GCs), ovarian folliculogenesis, oogenesis and early embryonic development in mice, but its role has never been investigated in other species. The aim of the present study was to characterize the AQP8 function in buffalo follicular development. The expression pattern of AQP8 in buffalo follicle was analysed by immunohistochemistry method. 17ß-Estradiol (E2) or oestrogen receptor antagonist ICI182780 was used to treat GCs cultured in vitro, and the expression of AQP8 was detected using qRT-PCR. Its roles in apoptosis of buffalo GCs were investigated by shRNA technology. AQP8 was found to be expressed higher in secondary follicles (p < .05), and its mRNA level in GCs was upregulated by E2 via receptor-mediated mechanism in a dose-dependent manner. A 732-bp buffalo AQP8 coding region was obtained, which was highly conserved at the amino acid level among different species. AQP8-shRNA2 had more effective inhibition on target gene than AQP8-shRNA1 (66.49% vs. 58.31%) (p < .05). Knockdown of AQP8 induced GCs arrested at G2/M stage and occurred apoptosis. Compared with the control group, higher Caspase9 expression were observed in AQP8-shRNA2 lentivirus infected GCs (p < .05), while Bcl-2 and Bax expression levels had no obvious change (p > .05). Altogether, the above results indicate that AQP8 is involved in oestrogen-mediated regulation of buffalo follicular development by regulating cell cycle progression and apoptosis of GCs.