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Whereas chronological age (CA) cannot distinguish functional differences among individuals of the same age, the biological age (BA) may be used to reflect the functional state of the body. The purpose of this study was to construct an integral formula of the BA, by using principle component analysis (PCA). The vital organ function of 505 healthy individuals of Han origin (age 35–91 years) was examined. A total of 114 indicators of cardiovascular, pulmonary, and brain functions, and clinical, inflammatory, genetic, psychological, and life habit factors were assessed as candidate indicators of aging. Candidate indicators were submitted with CA to correlation and redundancy analyses. The PCA method was used to build an integral formula of the BA for the population. Seven biomarkers were selected in accordance with a certain load standard. These biomarkers included the trail making test (TMT), pulse pressure (PP), mitral valve annulus ventricular septum of the peak velocity of early filling (MVES), minimum carotid artery intimalmedial thickness (IMTmin), maximum internal diameter of the carotid artery (Dmax), maximal midexpiratory flow rate 75/25 (MMEF75/25), and Cystatin C (CysC). The formula for the BA was: BA = 0.0685 (TMT) + 0.267 (PP)–1.375 (MVES) + 22.443 (IMTmin) + 2.962 (Dmax)–2.332 (MMEF75/25) + 16.104 (CysC) + 0.137 (CA) + 0.492. Several genetic and lifestyle indicators were considered as candidate markers of aging. However, ultimately, only markers reflecting the function of the vital organs were included in the BA formula. This study represents a useful attempt to employ multiple indicators to build a comprehensive BA evaluation formula of aging populations.

Certain gene polymorphisms are associated with human aging. This study investigated polymorphisms of a metabolism-related gene, Klotho, and an inflammatory gene, IL6, for association with the aging process in a healthy Han Chinese population. A total of 482 healthy subjects were recruited and divided into aging and young groups according to chronological age and biological age. Snapshots were used to detect a Klotho gene tag SNP (rs571118) and the F-SNPs rs9536314 (F352V) and rs9527025 (C370S), and an interleukin 6 (IL-6) gene tag SNP (rs1524107) and the F-SNPs rs1800795 (−174G/C) and rs1800796 (−572G/C). Klotho F352V and IL-6-174G/C was G homozygous, C370S was T homozygous while IL-6-572G/C MAF less than 5%. There was a statistically significant difference in the Klotho rs571118 SNP between chronological age groups, but not biological age groups. However, other SNPs, including IL-6 gene SNPs, didn’t correlate with age in the Han Chinese population. Human aging is a complex process that includes chronological and biological aging. Our current data showed that Klotho gene rs571118 SNP was associated with chronological aging, but not biological aging, in a Han Chinese population. Further study will investigate genetic build up for the difference between chronological and biological aging.

A 3D direct numerical simulation (DNS) study of the evolution of a self-propagating interface in forced constant-density statistically stationary homogeneous isotropic turbulence was performed by solving Navier–Stokes and level-set equations under a wide range of conditions that cover various (from 0.1 to 2.0) ratios of the interface speed  $S_{L}$  to the r.m.s. turbulent velocity  $U^{\\prime }$  and various (50, 100 and 200) turbulent Reynolds numbers $\\mathit{Re}$ . By analysing computed data, the following issues were addressed: (i) dependence of the speed and thickness of the fully developed statistically planar mean front that envelops the interface on $U^{\\prime }/S_{L}$ and $\\mathit{Re}$ , (ii) dependence of the fully developed mean turbulent flux of a scalar $c$ that characterizes the state of the fluid ( $c=0$ and 1 ahead and behind the interface respectively) on $U^{\\prime }/S_{L}$ and $\\mathit{Re}$ , (iii) evolution of the mean front speed, its thickness, and the mean scalar flux during the front development after embedding a planar interface into the forced turbulence and (iv) relation between canonical and conditioned moments of the velocity, velocity gradient and pressure gradient fields.

Background:Progressive pseudo-pseudorheumatoid dysplasia (PPRD) is a rare autosomal recessive non-inflammatory joint disorder characterized by articular cartilage involvement, resulting in progressive joint stiffness and enlargement without inflammation [1]. The pathogenesis of PPRD remains elusive, although mutations in the cellular communication network factor 6 (CCN6) have been directly associated with this condition.Objectives:Revealing the molecular mechanism underlying PPRD triggered by CCN6 mutation.Methods:Exome sequencing was performed on a PPRD pedigree to identify potential mutations. A lentivirus-based expression vector containing the identified CCN6 mutation was constructed and utilized for chondrocyte infection to simulate the cellular pathology observed in PPRD. Co-immunoprecipitation, confocal imaging, Western blotting, and flow cytometry were employed to analyze changes in cellular function.Results:Both affected individuals within the pedigree, including the patient and her sister, were diagnosed with PPRD. Exome sequencing revealed that the most frequently reported CCN6 mutation site among published Chinese literature on PPRD was C223G. Subsequent cell transfection experiments demonstrated that wild-type CCN6 localized to chondrocyte mitochondria while CCN6 (C223G) remained cytoplasmic. Further investigation revealed impaired interaction between mutant CCN6-C223G and mitochondrial chaperone HSP60 compared to wild-type CCN6-HSP60 binding, leading to abnormal HSP60 function. This activation of mitochondrial unfolded protein response (mtUPR) disrupted cellular energy metabolism and resulted in altered gene expression within the nucleus.Conclusion:The identification of the CCN6-C223G mutation sheds light on its role in triggering mtUPR and subsequent aberrant chondrocyte function in PPRD patients. These findings provide valuable insights for potential drug development targeting this molecular pathway implicated in PPRD.REFERENCES:[1] Wynne-Davies R, Hall C, Ansell BM: Spondylo-epiphysial dysplasia tarda with progressive arthropathy. A “new” disorder of autosomal recessive inheritance. The Journal of bone and joint surgery British volume 1982, 64(4):442-445.Acknowledgements:NIL.Disclosure of Interests:None declared.

Elastic electron–proton scattering (e–p) and the spectroscopy of hydrogen atoms are the two methods traditionally used to determine the proton charge radius, r p . In 2010, a new method using muonic hydrogen atoms 1 found a substantial discrepancy compared with previous results 2 , which became known as the ‘proton radius puzzle’. Despite experimental and theoretical efforts, the puzzle remains unresolved. In fact, there is a discrepancy between the two most recent spectroscopic measurements conducted on ordinary hydrogen 3 , 4 . Here we report on the proton charge radius experiment at Jefferson Laboratory (PRad), a high-precision e–p experiment that was established after the discrepancy was identified. We used a magnetic-spectrometer-free method along with a windowless hydrogen gas target, which overcame several limitations of previous e–p experiments and enabled measurements at very small forward-scattering angles. Our result, r p  = 0.831 ± 0.007 stat  ± 0.012 syst  femtometres, is smaller than the most recent high-precision e–p measurement 5 and 2.7 standard deviations smaller than the average of all e–p experimental results 6 . The smaller r p we have now measured supports the value found by two previous muonic hydrogen experiments 1 , 7 . In addition, our finding agrees with the revised value (announced in 2019) for the Rydberg constant 8 —one of the most accurately evaluated fundamental constants in physics. A magnetic-spectrometer-free method for electron–proton scattering data reveals a proton charge radius 2.7 standard deviations smaller than the currently accepted value from electron–proton scattering, yet consistent with other recent experiments.

The mammalian target of rapamycin (mTOR) signaling pathway is upregulated in the pathogenesis of many cancers. Arachidonic acid (AA) and its metabolites play critical role in the development of breast cancer, but the mechanisms through which AA promotes mammary tumorigenesis and progression are poorly understood. We found that the levels of AA and cytosolic phospholipase A2 (cPLA2) strongly correlated with the signaling activity of mTORC1 and mTORC2 as well as the expression levels of vascular epithelial growth factor (VEGF) in human breast tumor tissues. In cultured breast cancer cells, AA effectively activated both mTOR complex 1 (mTORC1) and mTORC2. Interestingly, AA-stimulated mTORC1 activation was independent of amino acids, phosphatidylinositol 3-kinase (PI3-K) and tuberous sclerosis complex 2 (TSC2), which suggests a novel mechanism for mTORC1 activation. Further studies revealed that AA stimulated mTORC1 activity through destabilization of mTOR–raptor association in ras homolog enriched in brain (Rheb)-dependent mechanism. Moreover, we showed that AA-stimulated cell proliferation and angiogenesis required mTOR activity and that the effect of AA was mediated by lipoxygenase (LOX) but not cyclooxygenase-2 (COX-2). In animal models, AA-enhanced incidences of rat mammary tumorigenesis, tumor weights and angiogenesis were inhibited by rapamycin. Our findings suggest that AA is an effective intracellular stimulus of mTOR and that AA-activated mTOR plays critical roles in angiogenesis and tumorigenesis of breast cancer.

Objectives There currently lacks a noninvasive and accurate method to distinguish benign and malignant ovarian lesion prior to treatment. This study developed a deep learning algorithm that distinguishes benign from malignant ovarian lesion by applying a convolutional neural network on routine MR imaging. Methods Five hundred forty-five lesions (379 benign and 166 malignant) from 451 patients from a single institution were divided into training, validation, and testing set in a 7:2:1 ratio. Model performance was compared with four junior and three senior radiologists on the test set. Results Compared with junior radiologists averaged, the final ensemble model combining MR imaging and clinical variables had a higher test accuracy (0.87 vs 0.64, p  < 0.001) and specificity (0.92 vs 0.64, p  < 0.001) with comparable sensitivity (0.75 vs 0.63, p  = 0.407). Against the senior radiologists averaged, the final ensemble model also had a higher test accuracy (0.87 vs 0.74, p  = 0.033) and specificity (0.92 vs 0.70, p  < 0.001) with comparable sensitivity (0.75 vs 0.83, p  = 0.557). Assisted by the model’s probabilities, the junior radiologists achieved a higher average test accuracy (0.77 vs 0.64, Δ = 0.13, p  < 0.001) and specificity (0.81 vs 0.64, Δ = 0.17, p  < 0.001) with unchanged sensitivity (0.69 vs 0.63, Δ = 0.06, p  = 0.302). With the AI probabilities, the junior radiologists had higher specificity (0.81 vs 0.70, Δ = 0.11, p  = 0.005) but similar accuracy (0.77 vs 0.74, Δ = 0.03, p  = 0.409) and sensitivity (0.69 vs 0.83, Δ = -0.146, p  = 0.097) when compared with the senior radiologists. Conclusions These results demonstrate that artificial intelligence based on deep learning can assist radiologists in assessing the nature of ovarian lesions and improve their performance. Key Points • Artificial Intelligence based on deep learning can assess the nature of ovarian lesions on routine MRI with higher accuracy and specificity than radiologists. • Assisted by the deep learning model’s probabilities, junior radiologists achieved better performance that matched those of senior radiologists.

Polycyclic aromatic hydrocarbons (PAHs) are common organic pollutants that can be transferred long distances and tend to accumulate in marine sediments. However, less is known regarding the distribution of PAHs and their natural bioattenuation in the open sea, especially the Arctic Ocean. In this report, sediment samples were collected at four sites from the Chukchi Plateau to the Makarov Basin in the summer of 2010. PAH compositions and total concentrations were examined with GC-MS. The concentrations of 16 EPA-priority PAHs varied from 2.0 to 41.6 ng g−1 dry weight and decreased with sediment depth and movement from the southern to the northern sites. Among the targeted PAHs, phenanthrene was relatively abundant in all sediments. The 16S rRNA gene of the total environmental DNA was analyzed with Illumina high-throughput sequencing (IHTS) to determine the diversity of bacteria involved in PAH degradation in situ. The potential degraders including Cycloclasticus, Pseudomonas, Halomonas, Pseudoalteromonas, Marinomonas, Bacillus, Dietzia, Colwellia, Acinetobacter, Alcanivorax, Salinisphaera and Shewanella, with Dietzia as the most abundant, occurred in all sediment samples. Meanwhile, enrichment with PAHs was initiated onboard and transferred to the laboratory for further enrichment and to obtain the degrading consortia. Most of the abovementioned bacteria in addition to Hahella, Oleispira, Oceanobacter and Hyphomonas occurred alternately as predominant members in the enrichment cultures from different sediments based on IHTS and PCR-DGGE analysis. To reconfirm their role in PAH degradation, 40 different bacteria were isolated and characterized, among which Cycloclasticus Pseudomonas showed the best degradation capability under low temperatures. Taken together, PAHs and PAH-degrading bacteria were widespread in the deep-sea sediments of the Arctic Ocean. We propose that bacteria of Cycloclasticus, Pseudomonas, Pseudoalteromonas, Halomonas, Marinomonas and Dietzia may play the most important role in PAH mineralization in situ.

Background:The epidemic of coronavirus disease 2019 (COVID-19) has brought a heavy burden to the world. It is worth to note that it shares many clinical symptoms with systemic lupus erythematosus (SLE), but whether there is a similar pathological process between them is not clear.Objectives:In this study, we analyzed the potentially similar pathogenesis between SLE and COVID-19, and explored their possible pharmacotherapy options using bioinformatics and systems biology approaches.Methods:The common differentially expressed genes (DEGs) were extracted from the COVID-19 datasets and the SLE datasets for functional enrichment, pathway analysis and candidate drug analysis.Results:Based on the two transcriptome datasets between COVID-19 and SLE, 325 common DEGs were selected. Hub genes were identified by protein-protein interaction (PPI) analysis. few found a variety of similar functional changes between COVID-19 and SLE, which may be related to the pathogenesis of COVID-19. Besides, we explored the related regulatory networks. Then, through drug target matching, we found many candidate drugs for patients with COVID-19 only or COVID-19 combined with SLE.Conclusion:COVID-19 and SLE patients share many common hub genes, related pathways and regulatory networks. Based on these common targets, we found many potential drugs that could be used in treating patient with COVID-19 or COVID-19 combined with SLE.Figure 1.Figure 2.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

The focal plane camera is the core component of the Wide Field-of-view Cherenkov/fluorescence Telescope Array (WFCTA) of the Large High-Altitude Air Shower Observatory (LHAASO). Because of the capability of working under moonlight without aging, silicon photomultipliers (SiPM) have been proven to be not only an alternative but also an improvement to conventional photomultiplier tubes (PMT) in this application. Eighteen SiPM-based cameras with square light funnels have been built for WFCTA. The telescopes have collected more than 100 million cosmic ray events and preliminary results indicate that these cameras are capable of working under moonlight. The characteristics of the light funnels and SiPMs pose challenges (e.g. dynamic range, dark count rate, assembly techniques). In this paper, we present the design features, manufacturing techniques and performances of these cameras. Finally, the test facilities, the test methods and results of SiPMs in the cameras are reported here.