Mutations of fibrillin‐1 (FBN1) have been associated with Marfan syndrome and pleiotropic connective tissue disorders, collectively termed as “type I fibrillinopathy”. However, few genotype–phenotype ...correlations are known in the ocular system. Patients with congenital ectopia lentis (EL) received panel‐based next‐generation sequencing, complemented with multiplex ligation‐dependent probe amplification. In a total of 125 probands, the ocular phenotypes were compared for different types of FBN1 mutations. Premature termination codons were associated with less severe EL and a thinner central corneal thickness (CCT) than the inframe mutations. The eyes of patients with mutations in the C‐terminal region had a higher incidence of posterior staphyloma than those in the middle and N‐terminal regions. Mutations in the TGF‐β‐regulating sequence had larger horizontal corneal diameters (white‐to‐white WTW), higher incidence of posterior staphyloma, but less severe EL than those with mutations in other regions. Mutations in the neonatal region were associated with thinner CCT. Longer axial length (AL) was associated with mutations in the C‐terminal region or TGF‐β regulating sequence after adjusting for age, EL severity, and corneal curvature radius. FBN1 genotype–phenotype correlations were established for some ocular features, including EL severity, AL, WTW, CCT, and so forth, providing novel perspectives and directions for further mechanistic studies.
Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats
. ...Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans
. Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor-angiotensin converting enzyme II (ACE2)-as SARS-CoV.
Fabricating a robust interfacial layer on the lithium metal anode to isolate it from liquid electrolyte is vital to restrain the rapid degradation of a lithium metal battery. Here, we report that the ...solution-processed metal chloride perovskite thin film can be coated onto the lithium metal surface as a robust interfacial layer to shield the lithium metal from liquid electrolyte. Via phase analysis and density functional theory calculations, we demonstrate that the perovskite layer can allow fast lithium ion shuttle under a low energy barrier of 0.45 eV without the collapse of framework. Such perovskite modification can realize stable cycling of LiCoO
|Li cells with an areal capacity of 2.8 mAh cm
using thin lithium metal foil (50 μm) and limited electrolyte (20 μl mAh
) for over 100 cycles at 0.5 C. The metal chloride perovskite protection strategy could open a promising avenue for advanced lithium metal batteries.
To evaluate the diagnostic yield of congenital ectopia lentis (EL) in a Chinese cohort by combining panel-based next-generation sequencing with clinical findings.
A cohort study.
In total, 175 ...patients with congenital EL and their available family members (n = 338) were enrolled. All patients with congenital EL underwent genetic testing. Genotype-phenotype analyses were conducted to assess the biometric and structural ocular manifestations of congenital EL.
In total, 175 patients with congenital EL and 338 of their relatives were included in this study. In these patients, 92.57% (162 of 175) of disease-related variants were detected in FBN1 (83.43%), CPAMD8 (1.71%), COL4A5 (0.57%), ADAMTSL4 (3.43%), LTBP2 (1.71%), and CBS (2.29%). Based on genetic and clinical findings, the primary diagnostic rate was increased to 40.57% from 19.43% with the exception of the 91 diagnoses of potential Marfan syndrome, with a new diagnostic strategy for congenital EL, thus having been developed. Within this group of patients harboring FBN1 mutations, 16.44% (19 of 141) probands were diagnosed with EL syndrome and 2.13% (3 of 141) were diagnosed with Marfan syndrome.
The results of this cohort study expand the genomic landscape associated with congenital EL in Chinese cohorts. FBN1 mutations represent the most common cause of congenital EL in this population, and we have developed a new diagnostic strategy for congenital EL subtypes via the use of a well-designed panel-based next-generation sequencing that can be used to efficiently and precisely diagnose patients with congenital EL in a cost-effective manner.
Pancreatic cancer (PC) represents a relatively rare but severe malignancy worldwide. Accumulated studies have emphasized the potential of long noncoding RNA (lncRNA) as therapeutic strategies for ...several human cancers. Thus, we aimed to investigate whether a novel non-coding RNA regulatory circuitry involved in PC. Aberrantly expressed lncRNAs and mRNAs were screened out of microarray database. Following the determination of RNA expression, PANC-1 and BxPC-3 PC cells were adopted, after which the expression of miR-330-5p, PAX8 and LINC00958 were subsequently altered. RNA crosstalk was validated by dual-luciferase reporter gene assay. In order to detect whether LINC00958 could act as ceRNA to competitively sponge miR-330-5p and regulate PAX8, subcellular location of LINC00958 and interaction between LINC00958 and miR-330-5p were measured by FISH and RNA pull down respectively. The epithelial mesenchymal transition (EMT) process, cell invasion, and tumor growth were determined in vitro and in vivo. LINC00958 and PAX8 were up-regulated, while miR-330-5p was down-regulated during PC. LINC00958 mainly expressed in the cytoplasm and LINC00958 competitively sponged miR-330-5p. Upregulated miR-330-5p or downregulated PAX8 inhibited the EMT process as well as the invasion and metastasis ability of the PC cells. Moreover, the results indicated that miR-330-5p negatively targeted PAX8, and LINC00958 ultimately showcasing its ability to bind to miR-330-5p through its interaction with AGO2. Therefore, silencing of LINC00958 may bind to miR-330-5p to inhibit PAX8 in a competitive fashion, thereby preventing the progression of PC.
•This study explores the effects of LINC00958 on PC via the miR-330-5p/PAX8 axis.•LINC00958 and PAX8 are highly expressed, yet miR-330-5p down-regulated in PC cells.•PAX8 is a target gene of miR-330-5p.•LINC00958 promotes PAX8 by binding with miR-330-5p in PC.•Down-regulated LINC00958 inhibits EMT, invasion, and metastasis of PC cells.
Lithospheric thinning and destruction of the North China Craton have been topics of active discussion throughout the last two decades, but the specific processes associated with lithospheric thinning ...remains controversial. Here we report co-occurrence of low-Ti (TiO2<1.1wt.%, Ti/Y<270) and high-Ti (TiO2>2wt.%, Ti/Y>370) types of lamprophyres in the Jiaodong Peninsula, eastern North China Craton in order to address this issue. Low-Ti lamprophyres are depleted in HFSE and enriched in Pb, both typical subduction signatures. We suggest they were derived from partial melting of an ancient and enriched lithospheric mantle, which was previously modified by slab-derived hydrous fluids. In contrast, the high-Ti lamprophyre has trace element patterns similar to many oceanic basalts with depletion of Pb but little or no HFSE depletion. We infer that they originated from partial melting of a convective asthenospheric mantle. Zircon U–Pb dating shows that both types of lamprophyres intruded the eastern North China Craton about 121Myr ago. Their indistinguishable ages thus appear to record a rapid transition from lithospheric to asthenospheric mantle source, suggesting further that the lithosphere beneath the eastern North China Craton was removed, potentially delaminated ca. 121Myr ago beneath Jiaodong Peninsula. The detachment of cratonic lithosphere is likely related to continental arc-rifting which resulted from Palaeo-Pacific plate subduction in the Mesozoic.
Abstract
The remarkable advances in next-generation sequencing technology have enabled the wide usage of sequencing as a clinical tool. To promote the advance of precision oncology for breast cancer ...in China, here we report a large-scale prospective clinical sequencing program using the Fudan-BC panel, and comprehensively analyze the clinical and genomic characteristics of Chinese breast cancer. The mutational landscape of 1,134 breast cancers reveals that the most significant differences between Chinese and Western patients occurred in the hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer subtype. Mutations in p53 and Hippo signaling pathways are more prevalent, and 2 mutually exclusive and 9 co-occurring patterns exist among 9 oncogenic pathways in our cohort. Further preclinical investigation partially suggests that
NF2
loss-of-function mutations can be sensitive to a Hippo-targeted strategy. We establish a public database (Fudan Portal) and a precision medicine knowledge base for data exchange and interpretation. Collectively, our study presents a leading approach to Chinese precision oncology treatment and reveals potentially actionable mutations in breast cancer.
A variety of nanomaterial‐based biosensors have been developed to sensitively detect biomolecules in vitro, yet limited success has been achieved in real‐time sensing in vivo. The application of ...microneedles (MN) may offer a solution for painless and minimally‐invasive transdermal biosensing. However, integration of nanostructural materials on microneedle surface as transdermal electrodes remains challenging in applications. Here, a transdermal H2O2 electrochemical biosensor based on MNs integrated with nanohybrid consisting of reduced graphene oxide and Pt nanoparticles (Pt/rGO) is developed. The Pt/rGO significantly improves the detection sensitivity of the MN electrode, while the MNs are utilized as a painless transdermal tool to access the in vivo environment. The Pt/rGO nanostructures are protected by a water‐soluble polymer layer to avoid mechanical destruction during the MN skin insertion process. The polymer layer can readily be dissolved by the interstitial fluid and exposes the Pt/rGO on MNs for biosensing in vivo. The applications of the Pt/rGO‐integrated MNs for in situ and real‐time sensing of H2O2 in vivo are demonstrated both on pigskin and living mice. This work offers a unique real‐time transdermal biosensing system, which is a promising tool for sensing in vivo with high sensitivity but in a minimally‐invasive manner.
Transdermal H2O2 electrochemical biosensors based on microneedles (MNs) integrated with nanohybrid consisting of reduced graphene oxide and Pt nanoparticles (Pt/rGO) are developed. The polyvinylpyrrolidone‐protected Pt/rGO significantly improves the detection sensitivity of the MN electrode, while the MNs are utilized as a painless transdermal tool to access the in vivo environment.
Abstract
We report the observations of FRB 20220912A using the Five-hundred-meter Aperture Spherical radio Telescope. We conducted 17 observations totaling 8.67 hr and detected a total of 1076 bursts ...with an event rate up to 390 hr
−1
. The cumulative energy distribution can be well described using a broken power-law function with the lower- and higher-energy slopes of −0.38 ± 0.02 and −2.07 ± 0.07, respectively. We also report the
L
-band (1–1.5 GHz) spectral index of the synthetic spectrum of FRB 20220912A bursts, which is −2.6 ± 0.21. The average rotation measure value of the bursts from FRB 20220912A is −0.08 ± 5.39 rad m
−2
, close to 0 rad m
−2
and was relatively stable over 2 months. Most bursts have nearly 100% linear polarization. About 45% of the bursts have circular polarization with Signal-to-Noise ratio > 3, and the highest circular polarization degree can reach 70%. Our observations suggest that FRB 20220912A is located in a relatively clean local environment with complex circular polarization characteristics. These various behaviors imply that the mechanism of circular polarization of FRBs likely originates from an intrinsic radiation mechanism, such as coherent curvature radiation or inverse Compton scattering inside the magnetosphere of the FRB engine source (e.g., a magnetar).
The utilization of dendritic cell (DC) vaccines is a promising approach in cancer immunotherapy, and the modification of DCs for the expression of tumor‐associated antigens is critical for successful ...cancer immunotherapy. A safe and efficient method for delivering DNA/RNA into DCs without inducing maturation is beneficial to achieve successful DC transformation for cell vaccine applications, yet remains challenging. This work presents a nanochannel electro‐injection (NEI) system for the safe and efficient delivery of a variety of nucleic acid molecules into DCs. The device is based on track‐etched nanochannel membrane as key components, where the nano‐sized channels localize the electric field on the cell membrane, enabling lower voltage (<30 V) for cell electroporation. The pulse conditions of NEI are examined so that the transfection efficiency (>70%) and biosafety (viability >85%) on delivering fluorescent dyes, plasmid DNA, messenger RNA, and circular RNA (circRNA) into DC2.4 are optimized. Primary mouse bone marrow DC can also be transfected with circRNA with 68.3% efficiency, but without remarkably affecting cellular viability or inducing DC maturation. These results suggest that NEI can be a safe and efficient transfection platform for in vitro transformation of DCs and possesses a promising potential for developing DC vaccines against cancer.
This work presents a nanochannel electro‐injection system for the safe and efficient delivery of a variety of nucleic acid molecules (DNA and RNA) into dendritic cells (DCs). The device is based on track‐etched nanochannel membrane as key components, where the nano‐sized channels localize the electric field on the cell membrane, enabling relatively low voltage (<30 V) for cell electroporation.
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