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Lysyl oxidase-like 2 (LOXL2) mediates the crosslinking of extracellular collagen, reflecting qualitative changes in liver fibrosis. This study aimed to validate the utility of serum LOXL2 levels as a predictive biomarker for the development of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) infection who achieved a sustained virological response (SVR). This retrospective study included 137 patients with chronic HCV infection without history of HCC development and who achieved SVR via direct-acting antiviral therapy. Median LOXL2 levels decreased significantly after SVR achievement (pre-Tx, 2.33 ng/mL; post-Tx, 1.31 ng/mL, p < 0.001). Post-Tx LOXL2 levels, fibrosis-4 index, platelet counts, Wisteria floribunda agglutinin-positive human Mac-2 binding protein levels, and alpha-fetoprotein (AFP) levels were identified as independent predictive factors for post-SVR HCC development in the univariate analysis. The incidence of post-SVR HCC development was significantly higher in patients with post-Tx LOXL2 levels ≥ 2.08 ng/mL and AFP levels ≥ 5.0 ng/mL than in patients with elevated levels of either marker or with lower marker levels. Serum LOXL2 levels can serve as a predictive biomarker for HCC development after achieving SVR. The combination of serum LOXL2 and AFP levels provides robust risk stratification for HCC development after SVR, suggesting an enhanced surveillance strategy., (© 2024. The Author(s).)

Homologous recombination (HR) repairs DNA damage including DNA double-stranded breaks and alterations in HR-related genes results in HR deficiency. Germline alteration of HR-related genes, such as BRCA1 and BRCA2, causes hereditary breast and ovarian cancer (HBOC). Cancer cells with HR deficiency are sensitive to poly (ADP-ribose) polymerase (PARP) inhibitors and DNA-damaging agents. Thus, accurately evaluating HR activity is useful for diagnosing HBOC and predicting the therapeutic effects of anti-cancer agents. Previously, we developed an assay for site-specific HR activity (ASHRA) that can quantitatively evaluate HR activity and detect moderate HR deficiency. HR activity in cells measured by ASHRA correlates with sensitivity to the PARP inhibitor, olaparib. In this study, we applied ASHRA to lymphoblastoid cells and xenograft tumor tissues, which simulate peripheral blood lymphocytes and tumor tissues, respectively, as clinically available samples. We showed that ASHRA could be used to detect HR deficiency in lymphoblastoid cells derived from a BRCA1 pathogenic variant carrier. Furthermore, ASHRA could quantitatively measure the HR activity in xenograft tumor tissues with HR activity that was gradually suppressed by inducible BRCA1 knockdown. The HR activity of xenograft tumor tissues quantitatively correlated with the effect of olaparib. Our data suggest that ASHRA could be a useful assay for diagnosing HBOC and predicting the efficacy of PARP inhibitors., (© 2024. The Author(s).)

In order to reveal the relationship between new urbanization and carbon emission to provide reference opinions for the construction of low-carbon urbanization, an evaluation system between new urbanization and carbon emission was constructed. Then their matching degree relationship was analyzed by coupling coordination degree model based on the data from 2012 to 2021 in Anhui Province, and their development trend from 2023 to 2032 was predicted by gray prediction model. The results show that: (1) New urbanization and carbon emission have the co-trend effect, and the consistency of core impact factors is relatively significant. Among them, the level of new urbanization increases from 0.058 in 2012 to 0.699 in 2021 and carbon emission development increases from 0.023 in 2012 to 0.165 in 2021, which both showing an upward trend. Meanwhile, social urbanization and population carbon emission are the core influencing factors. (2) The coupling coordination degree between new urbanization and carbon emission is low, but the synergy trend is optimistic and there is a large room for improvement. Among them, the coupling coordination coefficient of the coupling system rises from 0.136 in 2012 to 1.412 in 2021 (antagonistic phase), and then reaches 0.820 by 2032 (highly coordinated phase) by forecast. It shows that their current development is unbalanced, but the development trend is good, and there is a chance for improvement. This paper deepens the understanding of the logical correlation between new urbanization and carbon emission, and the following views are formed: (1) Low-carbon development is still the mainstream of new urbanization; (2) The coordination development of new urbanization and carbon emission reduction should be strengthened., (© 2023. The Author(s).)

Chimonobambusa hirtinoda, a threatened species, is only naturally distributed in Doupeng Mountain, Duyun, Guizhou, China. Next-generation sequencing (NGS) is used to obtain the complete chloroplast (cp) genome sequence of C. hirtinoda. The sequence was assembled and analyzed for phylogenetic and evolutionary studies. Additionally, we compared the cp genome of C. hirtinoda with previously published Chimonobambusa species. The cp genome of C. hirtinoda has a total length of 139, 561 bp and 38.90% GC content. This genome included a large single -copy (LSC) region of 83, 166 bp, a small single-copy (SSC) region of 20, 811 bp and a pair of inverted repeats of 21,792 bp each. We discovered 130 genes in the cp genome, including 85 protein-coding genes, 37 tRNA, and 8 rRNA genes. A total of 48 simple sequence repeats (SSRs) were detected. The A/U preference of the third nucleotide in the cp genome of C. hirtinoda was obtained by measuring the codon usage frequency of amino acids. Furthermore, phylogenetic analysis using complete cp sequences and matK gene revealed a genetic relationship within the Chimonobambusa genus. This study reported the chloroplast genome of the C. hirtinoda., (© 2022. The Author(s).)

Plate bending-related normal faults (i.e. bend-faults) develop at the outer trench-slope of the oceanic plate incoming into the subduction zone. Numerous geophysical studies and numerical simulations suggest that bend-faults play a key role by providing pathways for seawater to flow into the oceanic crust and the upper mantle, thereby promoting hydration of the oceanic plate. However, deep penetration of seawater along bend-faults remains controversial because fluids that have percolated down into the mantle are difficult to detect. This report presents anomalously high helium isotope ( 3 He/ 4 He) ratios in sediment pore water and seismic reflection data which suggest fluid infiltration into the upper mantle and subsequent outflow through bend-faults across the outer slope of the Japan trench. The 3 He/ 4 He and 4 He/ 20 Ne ratios at sites near-trench bend-faults, which are close to the isotopic ratios of bottom seawater, are almost constant with depth, supporting local seawater inflow. Our findings provide the first reported evidence for a potentially large-scale active hydrothermal circulation system through bend-faults across the Moho (crust-mantle boundary) in and out of the oceanic lithospheric mantle.

A ship-based seismic survey was conducted close to a fiber-optic submarine cable, and 50 km-long distributed acoustic sensing (DAS) recordings with air-gun shots were obtained for the first time. We examine the acquired DAS dataset together with the co-located hydrophones to investigate the detection capability of underwater acoustic (hydroacoustic) signals. Here, we show the hydroacoustic signals identified by the DAS measurement characterizing in frequency-time space. The DAS measurement can be sensitive for hydroacoustic signals in a frequency range from [Formula: see text] to a few tens of Hz which is similar to the hydrophones. The observed phases of hydroacoustic signals are coherent within a few kilometers along the submarine cable, suggesting the DAS is suitable for applying correlation analysis using hydroacoustic signals. Although our study suggests that virtual sensor's self-noise of the present DAS measurement is relatively high compared to the conventional in-situ hydroacoustic sensors above a few Hz, the DAS identifies the ocean microseismic background noise along the entire submarine cable except for some cable sections de-coupled from the seafloor.

The excision of genomic sequences using paired CRISPR-Cas nucleases is a powerful tool to study gene function, create disease models and holds promise for therapeutic gene editing. However, our understanding of the factors that favor efficient excision is limited by the lack of a rapid, accurate measurement of DNA excision outcomes that is free of amplification bias. Here, we introduce ddXR (droplet digital PCR eXcision Reporter), a method that enables the accurate and sensitive detection of excisions and inversions independent of length. The method can be completed in a few hours without the need for next-generation sequencing. The ddXR method uncovered unexpectedly high rates of large (> 20 kb) excisions and inversions, while also revealing a surprisingly low dependence on linear distance, up to 170 kb. We further modified the method to measure precise repair of excision junctions and allele-specific excision, with important implications for disease modeling and therapeutic gene editing.

Homologous recombination (HR) contributes to the repair of DNA double-strand breaks (DSBs) and inter-strand crosslinks. The HR activity in cancer cells can be used to predict their sensitivity to DNA-damaging agents that cause these damages. To evaluate HR activity, we developed a system called Assay for Site-specific HR Activity (ASHRA), in which cells are transiently transfected with an expression vector for CRISPR/Cas9 and a HR donor sequence containing a marker gene. DSBs are created by Cas9 and then repaired by HR using donor vector sequences homologous to the target gene. The level of genomic integration of the marker gene is quantified by Western blotting, flowcytometry, or quantitative PCR (qPCR). ASHRA detected HR deficiency caused by BRCA1, BARD1, or RAD51 knockdown or introduction of BRCA1 variants. The influence of BRCA1 variants on HR, as determined by qPCR, was consistent with the chemosensitivities of the transfected cells. The qPCR format of ASHRA could measure HR activity in both transcribed and un-transcribed regions. Knockdown of BRCA1 nor BARD1 did not affect HR activity in a transcriptionally inactive site. ASHRA can evaluate HR activity and will be useful for predicting sensitivity to chemotherapy, screening drugs that affect HR, and investigating the mechanisms of HR.

The interactions of the lithospheric plates that form the Earth's outer shell provide much of the evidentiary basis for modern plate tectonic theory. Seismic discontinuities in the lithosphere arising from mantle convection and plate motion provide constraints on the physical and chemical properties of the mantle that contribute to the processes of formation and evolution of tectonic plates. Seismological studies during the past two decades have detected seismic discontinuities within the oceanic lithosphere in addition to that at the lithosphere-asthenosphere boundary (LAB). However, the depth, distribution, and physical properties of these discontinuities are not well constrained, which makes it difficult to use seismological data to examine their origin. Here we present new active-source seismic data acquired along a 1,130 km profile across an old Pacific plate (148-128 Ma) that show oceanic mid-lithosphere discontinuities (oceanic MLDs) distributed 37-59 km below the seafloor. The presence of the oceanic MLDs suggests that frozen melts that accumulated at past LABs have been preserved as low-velocity layers within the current mature lithosphere. These observations show that long-offset, high-frequency, active-source seismic data can be used to image mid-lithospheric structure, which is fundamental to understanding the formation and evolution of tectonic plates.

Microinjection is considered the gold standard technique for delivery of nucleic acids (NAs; transgenes or genome editing tools such as CRISPR/Cas9 systems) into embryos, for creating genetically modified organisms. It requires sophisticated equipment as well as well-trained and highly skilled personnel to perform the micro-injection technique. Here, we describe a novel and simple microinjection-independent technique, called Genome-editing via Oviductal Nucleic Acids Delivery (GONAD). Using GONAD, we show that NAs (e.g., eGFP mRNA or Cas9 mRNA/sgRNAs) can be effectively delivered to pre-implantation embryos within the intact mouse oviduct by a simple electroporation method, and result in the desired genetic modification in the embryos. Thus GONAD can bypass many complex steps in transgenic technology such as isolation of zygotes, microinjection of NAs into them, and their subsequent transfer to pseudo-pregnant animals. Furthermore, this method can potentially be used for genome editing in species other than mice.

The junctional epithelium (JE) is an epithelial component that is directly attached to the tooth surface and has a protective function against periodontal diseases. In this study, we determined the origin of the JE using a bioengineered tooth technique. We transplanted the bioengineered tooth germ into the alveolar bone with an epithelial component that expressed green fluorescence protein. The reduced enamel epithelium from the bioengineered tooth fused with the oral epithelium, and the JE was apparently formed around the bioengineered tooth 50 days after transplantation. Importantly, the JE exhibited green fluorescence for at least 140 days after transplantation, suggesting that the JE was not replaced by oral epithelium. Therefore, our results demonstrated that the origin of the JE was the odontogenic epithelium, and odontogenic epithelium-derived JE was maintained for a relatively long period.