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A synthetic lethality-based strategy has been developed to identify therapeutic targets in cancer harboring tumor-suppressor gene mutations, as exemplified by the effectiveness of poly ADP-ribose polymerase (PARP) inhibitors in BRCA1/2-mutated tumors. However, many synthetic lethal interactors are less reliable due to the fact that such genes usually do not perform fundamental or indispensable functions in the cell. Here, we developed an approach to identifying the "essential lethality" arising from these mutated/deleted essential genes, which are largely tolerated in cancer cells due to genetic redundancy. We uncovered the cohesion subunit SA1 as a putative synthetic-essential target in cancers carrying inactivating mutations of its paralog, SA2. In SA2-deficient Ewing sarcoma and bladder cancer, further depletion of SA1 profoundly and specifically suppressed cancer cell proliferation, survival, and tumorigenic potential. Mechanistically, inhibition of SA1 in the SA2-mutated cells led to premature chromatid separation, dramatic extension of mitotic duration, and consequently, lethal failure of cell division. More importantly, depletion of SA1 rendered those SA2-mutated cells more susceptible to DNA damage, especially double-strand breaks (DSBs), due to reduced functionality of DNA repair. Furthermore, inhibition of SA1 sensitized the SA2-deficient cancer cells to PARP inhibitors in vitro and in vivo, providing a potential therapeutic strategy for patients with SA2-deficient tumors. [ABSTRACT FROM AUTHOR]

In addition to regulating growth and development, the most important function of microRNAs (miRNAs) in plants is the regulation of a variety of cellular processes underlying plant adaptation to environmental stresses. To gain a deep understanding of the mechanism of drought tolerance in rice, genome-wide profiling and analysis of miRNAs was carried out in drought-challenged rice across a wide range of developmental stages, from tillering to inflorescence formation, using a microarray platform. Among the 30 miRNAs identified as significantly down- or up-regulated under the drought stress, 11 down-regulated miRNAs (miR170, miR172, miR397, miR408, miR529, miR896, miR1030, miR1035, miR1050, miR1088, and miR1126) and eight up-regulated miRNAs (miR395, miR474, miR845, miR851, miR854, miR901, miR903, and miR1125) were revealed for the first time to be induced by drought stress in plants, and nine (miR156, miR168, miR170, miR171, miR172, miR319, miR396, miR397, and miR408) showed opposite expression to that observed in drought-stressed Arabidopsis. The most conserved down-regulated miRNAs were ath-miR170, the miR171 family, and ath-miR396, and the most conserved up-regulated miRNAs were ptc-miR474 and ath-miR854a. The identification of differentially expressed novel plant miRNAs and their target genes, and the analysis of cis-elements provides molecular evidence for the possible involvement of miRNAs in the process of drought response and/or tolerance in rice. [ABSTRACT FROM PUBLISHER]

Long-term antiviral treatment is necessary for chronic hepatitis B (CHB) patients, and treatment safety is imperative for these patients. Previous studies showed tenofovir alafenamide (TAF) has shown efficacy non-inferior to that of tenofovir disoproxil fumarate (TDF) with improved renal and bone safety. However, there is still a lack of a rapid and convenient method to identify CHB patients at high risk of osteoporosis before initiating antiviral treatment. The International Osteoporosis Foundation (IOF) recommended a one-minute osteoporosis risk test to identify early high-risk patients. Our aim was to evaluate the feasibility of the one-minute osteoporosis risk test, along with evaluating the effectiveness and safety for virologically suppressed CHB patients switching to TAF. Methods • In this multicenter, prospective study, patients with chronic HBV infection who had been receiving TDF or Entecavir (ETV) for 48 weeks or more with HBV DNA less than 20 IU/mL for longer than 6 months were screened by one-minute osteoporosis risk test. Patients with a high risk of osteoporosis and then diagnosed with osteopenia or osteoporosis by dual-energy X-ray absorptiometry (DEXA) were enrolled. Safety in bone and bone turnover markers and antiviral efficacy of TAF were assessed respectively at 24 and 48 weeks. Results • 84.95% (175/206) CHB patients screened by one-minute osteoporosis risk test were at risk of osteoporosis.85.71% (150/175) were diagnosed with osteopenia by DEXA. The analysis included a total of 138 patients, of whom 92(62.3%) were male and 46 (37.7%) were female, with a mean age of 45 years old. HBV DNA was suppressed at 48 weeks at 88% (35/40) in the prior ETV group and 90% (88/98) at 48 weeks group in the prior TDF group. Bone mineral density (BMD) of the lumbar spine (L1-L4) from TDF switching to TAF was improved at 24 weeks (1.03±0.11 vs. 0.97±0.12, P = .001) than baseline. Propeptides of type I procollagen (PINP) and beta-C-terminal telopeptides of type 1 collagen (CTX) in serum at 24 weeks after switching from TDF to TAF declined compared with baseline (50.35±18.90 vs. 63.65±19.17, P = .016 and 0.21±0.13 vs. 0.32±0.10, P = .017). BMD, PINP, and CTX in ETV to TAF group remained stable during treatment. Conclusion • Attention should be paid to osteoporosis risk during lone-term nucleot(s)ide analogue treatment. One minute test of osteoporosis risk could rapidly identify most CHB patients at risk of osteoporosis. Given its convenience, we recommend using this test for early screening in CHB patients prior to initiating antiviral treatment. Our results further demonstrated that an improvement in bone safety after switching to TAF in virologically suppressed CHB patients with osteoporosis. [ABSTRACT FROM AUTHOR]

Cu(OH)2and CuO nanoribbon arrays have been facilely fabricated on copper foil by silver-mediated oxidation in the mixed aqueous solution of Na2O2and AgNO3at room temperature. [ABSTRACT FROM AUTHOR]

Oncolytic virotherapy has emerged as a promising treatment for human cancers owing to an ability to elicit curative effects via systemic administration. Tumor cells often create an unfavorable immunosuppressive microenvironment that degrade viral structures and impede viral replication; however, recent studies have established that viruses altered via genetic modifications can serve as effective oncolytic agents to combat hostile tumor environments. Specifically, oncolytic vaccinia virus (OVV) has gained popularity owing to its safety, potential for systemic delivery, and large gene insertion capacity. This review highlights current research on the use of engineered mutated viruses and gene-armed OVVs to reverse the tumor microenvironment and enhance antitumor activity in vitro and in vivo, and provides an overview of ongoing clinical trials and combination therapies. In addition, we discuss the potential benefits and drawbacks of OVV as a cancer therapy, and explore different perspectives in this field. [ABSTRACT FROM AUTHOR]

An abstract of the article "Kaposi's Sarcoma-Associated Herpesvirus-Encoded MicroRNA miR-K12-11 Attenuates Transforming Growth Factor Beta Signaling through Suppression of SMAD5," by Rui Sun and colleagues is presented.

Replication and transcription activator (RTA) encoded by open reading frame 50 (ORF50) of Kaposi's sarcoma-associated herpesvirus (KSHV) is essential and sufficient to initiate lytic reactivation. RTA activates its target genes through direct binding with high affinity to its responsive elements or by interaction with cellular factors, such as RBP-Jκ, Ap-1, C/EBP-κ, and Oct-1. In this study, we identified transducin-like enhancer of split 2 (TLE2) as a novel RTA binding protein by using yeast two-hybrid screening of a human spleen cDNA library. The interaction between TLE2 and RTA was confirmed by glutathione S-transferase (GST) binding and coimmunoprecipitation assays. Immunofluorescence analysis showed that TLE2 and RTA were colocalized in the same nuclear compartment in KSHV-infected cells. This interaction recruited TLE2 to RTA bound to its recognition sites on DNA and repressed RTA auto-activation and transactivation activity. Moreover, TLE2 also inhibited the induction of lytic replication and virion production driven by RTA. We further showed that the Q (Gln-rich), SP (Ser-Pro-rich), and WDR (Trp-Asp repeat) domains of TLE2 and the Pro-rich domain of RTA were essential for this interaction. RBP-Jκ has been shown previously to bind to the same Pro-rich domain of RTA, and this binding can be subject to competition by TLE2. In addition, TLE2 can form a complex with RTA to access the cognate DNA sequence of the RTA-responsive element at different promoters. Intriguingly, the transcription level of TLE2 could be upregulated by RTA during the lytic reactivation process. In conclusion, we identified a new RTA binding protein, TLE2, and demonstrated that TLE2 inhibited replication and transactivation mediated by RTA. This provides another potentially important mechanism for maintenance of KSHV viral latency through interaction with a host protein. [ABSTRACT FROM AUTHOR]

The 12 May 2008 Wenchuan Ms8.0 earthquake produced surface displacements along the causative fault, the Yingxiu-Beichuan Fault, which are up to several meters near the fault. Because of the large gradient, satellite synthetic aperture radar (SAR) interferometric data are strongly incoherent; the usual SAR interferometry method does not allow such displacements to be measured. In the present study, we employed another approach, the technique based on pixel offset tracking, to solve this problem. The used image data of six tracks are from the Advanced Land Observing Satellite, Phased Array type L-band Synthetic Aperture Radar (ALOS/PALSAR) dataset of Japan. The results show that the entire surface rupture belt is 238 km long, extending almost linearly in a direction of 42° north-east. It is offset left laterally by a north-west-striking fault at Xiaoyudong, and turns at Gaochuan, where the rupture belt shifts toward the south by 5 km, largely keeping the original trend. In terms of the features of the rupture traces, the rupture belt can be divided into five sections and three types. Among them, the Beichuan-Chaping and Hongkou-Yingxiu sections are relatively complex, with large widths and variable traces along the trend. The Pingtong-Nanba and Qingping-Jingtang sections appear uniform, characterized by straight traces and small widths. West of Yingxiu, the rupture traces are not clear. North of the rupture belt, surface displacements are 2.95 m on average, mostly 2-3.5 m, with 7-9 m the maximum near Beichuan. South of the rupture belt, the average displacement is 1.75 m, dominated by 1-2 m, with 3-4 m at a few sites. In the north, the displacements in the radar line of sight are of subsidence, and in the south, they are uplifted, in accordance with a right-slip motion that moves the northern wall of the fault to the east, and the southern wall to the west, respectively. Along the Guanxian-Jiangyou Fault, there is a uplift zone in the radar line of sight, which is 66 km long, 1.5-6 km wide, and has vertical displacements of approximately 2 m, but no observable rupture traces. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) is a chronic disease causing severe impairment to the respiratory system and digestive tracts. Currently, CF is incurable. As an autosomal recessive disorder, the morbidity of CF is significantly higher among Caucasians of European descent, whereas it is less pervasive among African and Asian populations. The disease is caused by identical mutations (homozygosity) or different mutations (heterozygosity) of an autosomal recessive mutation at position 7q31.2‑q31.1 of chromosome 7. Diagnostic criteria and guidelines work concurrently with laboratory detection to facilitate precise CF detection. With technological advances, the understanding of CF pathogenesis has reached an unprecedented level, allowing for increasingly precise carrier screening, more effective early stage CF intervention and improved prognostic outcomes. These advances significantly increase the life quality and expectancy of patients with CF. Given the numerous improvements in the field of CF, the current review summarized the technical advances in the study of the molecular mechanisms underlying CF, as well as how these improvements facilitate the clinical outcomes of CF. Furthermore, challenges and obstacles to overcome are discussed. [ABSTRACT FROM AUTHOR]

We analyzed Sentinel-1A (S1A)/IW satellite descending data from multiple acquisitions to map coseismic and post-seismic deformation fields and invert the fault slip and afterslip models associated with the seismic moment magnitude (Mw)8.3 earthquake that occurred at Illapel, Chile, on September 16th, 2015. We generated one coseismic and four post-seismic interferograms to analyze temporal and spatial variations in the deformation field after the mainshock; we found that the coseismic deformation field has a semicircular shape and covers a 300-km long and 190-km wide area. The maximum displacement reaches ca. 1.33 m in the LOS subsidence direction, while post-seismic deformation derived from four interferograms with different time intervals is mainly distributed within a long narrow area approximately 65 km wide. Maximum displacement is ca. 8 cm, including two regions of line of sight (LOS) uplift and sinking. Major regions of deformation exhibit opposite directions to the mainshock just after the event, before reverting to consistency. We inverted the coseismic fault slip and afterslip models based on a shallow-dip single fault plane in a homogeneous elastic half space. Our inversion suggests that coseismic slip is mainly concentrated in a shallow region to the northwest of the source, and that rupture length along strike is close to 340 km, with a maximum slip of about 8.16 m to the trench. The estimated moment is 3.126 × 10 21 N m (Mw8.27), and the maximum rupture depth is 50 km. Inverted residual slip also shows just one region of slip in the shallow subsurface, which is shifted slightly to the south. In the early stage of deformation, the residual is along the down-dip direction, with a maximum value of ca. 32 cm, before turning into the up-dip direction, with a maximum value of ca. 23 cm. Finally, we present a preliminary analysis of these complex changes in space and time. [ABSTRACT FROM AUTHOR]

Oxidation of 5-methyl cytosine in DNA by ten-eleven translocation (Tet) family of enzymes has been demonstrated to play a significant role in epigenetic regulation in mammals. We found that Tet enzymes also possess the activity of catalyzing the formation of 5- hydroxymethylcytidine (5-hmrC) in RNA in vitro. In addition, the catalytic domains of all three Tet enzymes as well as full-length Tet3 could induce the formation of 5- hmrC in human cells. Moreover, 5-hmrC was present at appreciable levels (~1 per 5000 5-methylcytidine) in RNA of mammalian cells and tissues. Our results suggest the involvement of this oxidation in RNA biology. [ABSTRACT FROM AUTHOR]

Active DNA demethylation is an important part of epigenetic regulation in plants and animals. How active DNA demethylation is regulated and its relationship with histone modification patterns are unclear. Here, we report the discovery of IDM1, a regulator of DNA demethytation in Arabidopsis. IDM1 is required for preventing DNA hypermethylation of highly homologous multicopy genes and other repetitive sequences that are normally targeted for active DNA demethylation by Repressor of Silencing 1 and related 5-methytcytosine DNA glycosylases. IDM1 binds methylated DNA at chromatin sites lacking histone H3K4 di- or trimethylation and acetylates H3 to create a chromatin environment permissible for 5-methytcytosine DNA glycosylases to function. Our study reveals how some genes are indicated by multiple epigenetic marks for active DNA demethylation and protection from silencing. [ABSTRACT FROM AUTHOR]

On 21 March 2008, a Ms7.3 earthquake occurred at Quickbird, Yutian County, Xinjiang. We attempt to reveal the features of the causative fault of this shock and its coseismic deformation field. Our work is based on analysis and interpretation to high-resolution satellite images as well as differential interferometric synthetic aperture radar (D-InSAR) data from the satellite Envisat SAR, coupled with seismicity, focal mechanism solutions and active tectonics in this region. The result shows that the 40 km-long, nearly NS trending surface rupture zone by this event lies on a range-front alluvial platform in Qira County. It is characterized by distinct linear traces and simple structure with 1-3-m-wide individual seams and maximum 6.5 m width of a collapse fracture. Along the rupture zone many secondary fractures and fault-bounded blocks are seen, exhibiting remarkable extension. The coseismic deformation affected a large area 100 × 100 km2. D-InSAR analysis indicates that the interferometric deformation field is dominated by extensional faulting with a small strike-slip component. Along the causative fault, the western wall fell down and the eastern wall, that is the active unit, rose up, both with westerly vergence. Because of the big deformation gradients near the seismogenic fault, no interference fringes are seen on images, and what can be determined is a vertical displacement 70 cm or more between the two fault walls. According to the epicenter and differential occurrence times from the National Earthquake Information Center, China Earthquake Network Center, Harvard and USGS, it is suggested that the seismic fault ruptured from north to south. [ABSTRACT FROM AUTHOR]

The article focuses on findings of a study on analysis on preferred flowing path in shallow water delta front based on reservoir architecture. Topics include significance of identification of preferred flowing path in reducing the adverse effects on the oilfield development; role distribution of preferred flowing path in providing the basis for the prediction of residual oil distribution; and distributary channel based on deposition process.

We carry out an integrated study on coseismic and post-seismic deformation caused by 2010 Yushu earthquake sequence, including both mainshock and aftershocks, by using multi-scene ENVISAT/ASAR data on two adjacent tracks. We map the extended deformation region to the west of mainshock and show the westward extension of seismogenic fault of mainshock. Based on our whole deformation field derived from mosaic interferograms, the total length of seismogenic fault reaches ∼ 103 km longer than ∼ 71 km suggested by the previous report. Several coseismic interferograms with different time baselines have similar deformation patterns, which indicate that the influence of aftershocks and post-seismic slip on coseismic deformation field is limited. Also, we observe a clear and separate deformation area, ∼ 38 km to the west of the mainshock epicentre, with maximum displacement of ∼ 9 cm . The localised deformation is composed of two patches with opposite motion directions, where an aftershock cluster with at least 47 events ( > Ms 3.0 ) occurred. We infer that this localised deformation is caused by aftershocks ruptured on a blind active fault. While a weak post-seismic deformation band along main rupture zone near mainshock epicentre is likely attributable to short-term afterslip. [ABSTRACT FROM AUTHOR]