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Abstract Near miscibility widely exists in carbon dioxide (CO2) injection development projects. However, there is no existing approach to quantify the effect of near miscibility on oil recovery. In this paper, slim tube experiments were conducted to study near miscible region. The oil displacement efficiency curve is divided into immiscibility, near miscibility and miscibility. And three linear function is obtained, respectively. Then, the space between production well and CO2 injection well is discrete to characterize the effect of near miscibility on oil recovery. Then, a new approach is proposed to calculate oil recovery of CO2 displacement in tight oil reservoirs. This approach can calculate oil recovery considering near miscibility. It is found that minimum miscibility pressure (MMP) without considering near miscibility is 4 MPa lower than considering near miscibility. The near miscible pressure range is from 0.77 times to 1 time MMP considering near miscibility. Oil displacement efficiency difference reaches to be the maximum when the pressure is the minimum miscibility pressure without considering near miscibility. The maximum of the oil displacement efficiency difference is 3.4%. The optimal formation pressure considering near miscibility is 5 MPa larger than that without considering near miscibility. The oil recovery considering near miscibility is from 0.9 to 1.3% lower than that not considering near miscibility. It reaches to be the maximum when the pressure is the optimal formation pressure level without considering near miscibility. The maximum of the oil recovery difference is 1.3%.

Abstract Intestinal ischemia/reperfusion (I/R) injury is a typical pathological course in the clinic with a high morbidity rate. Recent research has pointed out the critical role of ubiquitination during the occurrence and development of intestinal I/R by precisely mediating protein quality control and function. Here, we conducted an integrated multiomic analysis to identify critical ubiquitination-associated molecules in intestinal I/R and identified endoplasmic reticulum-located HRD1 as a candidate molecule. During intestinal I/R, excessive ER stress plays a central role by causing apoptotic pathway activation. In particular, we found that ER stress-mediated apoptosis was mitigated by HRD1 knockdown in intestinal I/R mice. Mechanistically, TMEM2 was identified as a new substrate of HRD1 in intestinal I/R by mass spectrometry analysis, which has a crucial role in attenuating apoptosis and promoting non-canonical ER stress resistance. A strong negative correlation was found between the protein levels of HRD1 and TMEM2 in human intestinal ischemia samples. Specifically, HRD1 interacted with the lysine 42 residue of TMEM2 and reduced its stabilization by K48-linked polyubiquitination. Furthermore, KEGG pathway analysis revealed that TMEM2 regulated ER stress-mediated apoptosis in association with the PI3k/Akt signaling pathway rather than canonical ER stress pathways. In summary, HRD1 regulates ER stress-mediated apoptosis through a non-canonical pathway by ubiquitinating TMEM2 and inhibiting PI3k/Akt activation during intestinal I/R. The current study shows that HRD1 is an intestinal I/R critical regulator and that targeting the HRD1/TMEM2 axis may be a promising therapeutic approach.

TargetWe executed a Mendelian randomization (MR) investigation employing two distinct cohorts of genetic instrumental variables to elucidate the causal nexus between age at menarche (AAM) and the incidence of disparate breast cancer (BC) subtypes, in addition to the incidence of BC among first-degree kin.MethodsWe aggregated statistical data pertaining to AAM and BC from various consortia representing a homogenous population cohort. MR analysis was conducted employing inverse variance weighted (IVW) methodology as the principal approach, complemented by weighted median and MR-Egger regression techniques for an exhaustive evaluation. To evaluate the presence of pleiotropy, we applied the MR-Egger intercept test, MR-PRESSO, and leave-one-out sensitivity analysis.ResultsUpon exclusion of confounding SNP, an increment of one standard deviation in AAM was inversely correlated with the incidence of BC. (odds ratio [OR] 0.896, 95% confidence interval [CI] 0.831–0.968)/(OR 0.998, 95% CI 0.996–0.999) and estrogen receptor-positive (ER+) BC incidence (OR 0.895, 95% CI 0.814–0.983). It was also associated with reducing the risk of maternal BC incidence (OR 0.995, 95% CI 0.990–0.999) and sibling BC incidence (OR 0.997, 95% CI 0.994–0.999). No significant association was found between AAM and estrogen receptor-negative (ER-) BC incidence (OR 0.936, 95% CI 0.845–1.037).ConclusionOur study substantiated the causal relationship between a delayed AAM and a diminished risk of BC in probands, as well as in their maternal progenitors and siblings. Furthermore, the analysis suggests that AAM exerts a considerable potential causal influence on the risk of developing Luminal-a/b subtype of BC.

Abstract Background To evaluate the aqueous humor (AH) levels of cytokines in primary open-angle glaucoma (POAG) patients and cataract patients. Methods Thirty-eight POAG patients and 26 cataract patients were recruited. Peripheral blood (PB) was collected from each subject. The POAG group was divided into 2 subgroups according to the severity of visual field defects. The cutoff point of the mean deviation (MD) of the visual field was -12 dB. AH was obtained at the time of anterior chamber puncture during cataract or glaucoma surgery by using a 27-gauge needle attached to a microsyringe. AH and PB levels of interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta2 (TGF-β2) and IL-4 were assayed by enzyme-linked immunosorbent assay. Postoperative intraocular pressures (IOPs) of POAG patients were recorded during the follow-up period. Results TNF-α and TGF-β2 showed significantly higher AH levels in the POAG group than in the cataract group (P -12 dB and POAG patients with MD≤ -12 dB (P = 0.001). AH levels of TNF-α were significantly positively associated with IOP reduction after trabeculectomy (P = 0.025). AH and PB levels of cytokines were not related to the long-term success of trabeculectomy. Conclusion The levels of TNF-α and TGF-β2 showed different profiles in POAG patients and cataract patients. AH levels of TGF-β2 were correlated with the severity of glaucomatous neuropathy in POAG patients. The findings suggest possible roles for cytokines in the pathogenesis and development of POAG.

Background: Hearing loss is found in more than 5 % of cases worldwide. Hearing loss is divided into three types: Sensorineural hearing loss, Combined hearing loss and Conductive hearing loss. Among them, no less than 50 % of pediatric cases of sensorineural hearing loss are genetic. In Henan, China, there are no statistics on the allele frequency of deafness gene variants. Methods: We divided 2178 subjects enrolled at the Third Affiliated Hospital of Zhengzhou College from January 2019 to March 2021 into a hearing loss group and a normal control group. We performed array and pathogenicity classification for screening the 15 deafness gene variants, calculated and compared the allele frequency of the deafness gene variants, and then compared the hearing loss diagnosis rate between the hearing loss group and the normal control group. Results: We found that in the hearing loss group, the overall allele frequency of all detected variants was 16.6 %. Comparative analysis showed that the allele frequencies of GJB2 c.235delC variant, GJB3 c.538C > T variant and SLC26A4 c.919-2A > G variant were significantly higher than those of the East Asian population average in the gnomAD database. At the same time, our study confirmed that GJB3 c.538C > T variant may not be the disease-causing variant of hearing loss. Conclusions: These results support genetic counseling and rational prediction of risk for deafness.

Abstract Using the phase change characteristics of fixed points to trace the temperature of a spaceborne calibration blackbody is an important technical means to carry out the high-precision on-orbit calibration of thermal infrared remote sensors. In contrast to an experimental environment on the ground, a fixed point will produce radiation damage in the high-energy cosmic rays environment and may affect the phase change characteristics. This study investigates the effect of radiation damage caused by cosmic rays irradiation on the phase change characteristics of fixed points in a spaceborne calibration blackbody. In this research, the simulation method of molecular dynamics was used to simulate the irradiation damage effect of a strong cosmic rays environment on fixed-point indium (In). The experimental system was established to measure the phase change curves of samples with different irradiation doses, and then, the influence of irradiation on the phase change characteristics of the samples was analyzed. The results showed that most of the energy of irradiation was deposited on the In fixed point, resulting in the migration of 0.3% of the displacement atoms inside the In to the gap position to form the Frenkel pairs (FPs). The overcooling of the irradiated In fixed point was reduced by 0.3 $$^\circ \hbox {C}$$ ∘ C , the phase change temperature was increased by 30 mK, and the phase change plateau was more stable.

To evaluate the effectiveness of using airguns as seismic sources in inland waters to detect the regional crustal structure, a mobile large-capacity airgun excitation experiment was conducted in October 2015 in the Anhui section of the middle–lower Yangtze metallogenic belt. In this study, we extracted 1,957 first-arrival phases (Pg) and 2,179 Moho reflection phases (PmP) from the airgun seismic signals, and performed joint inversion of the traveltimes. The inversion results reveal the P-wave high-velocity anomalies above 7 km depth in the upper crust beneath the ore clustering areas, suggesting the source of mineralized materials. The crustal velocity structure characteristics substantially differed above and below a depth of 7 km, indicating the existence of a regional basement detachment surface. The velocity structure in the middle–lower crust, especially in the lower crust show lateral uniformity characteristic, which could be related to that the middle–lower Yangtze metallogenic belt had undergone a MASH metallization process. The Moho is 30–36 km deep, and its uplift zone extends from southwest to northeast in a “V” shape, which is consistent with the planar spreading characteristics of the metallogenic belt, indicating that the asthenosphere uplift and crustal thinning have had a controlling effect on the formation of the metallogenic belt. This study suggests the present-day crust in the region along the Yangtze River in Anhui retains the traces of lithosphere delamination-thinning and basaltic magma underplating during the Yanshan period. Our results indicates that airgun source detection in inland waters can effectively determine the continental crustal structure.

To understand the shallow structure and complex sedimentary environment of the 2017 Jinghe Ms6.6 earthquake focal area, we used one mouth of continuous sesimic data from a dense seismic array of 208 short period stations around the earthquake focal area, and applied the ambient noise tomography (ANT) method to image the three-dimensional Shear wave velocity structure at the depth less than 4 km. The shear wave velocity shown clear lateral variations and vertical variations from the surface to the deeper regions and has a tight correlation with surface geological and tectonic features in the study area. Obvious low-velocity anomalies has been presented throughout most of the Jinghe depression, whereas the Borokonu Mountains presented high-velocity anomalies. The thickness of the Cenozoic sedimentary basement in the study area is approximately 1–4 km, and the distribution of thickness is highly uneven. The crystalline basement in the study area has strong bending deformation, and the non-uniform Cenozoic sediments are related to the strong bending deformation of the crystalline basement. The Kusongmuchik piedmont fault is a high-angle thrust fault cutting through the base. There are also many medium low-angle faults, which do not penetrate the surface, which has indicated that they are in a concealed state at present. The results have provided a shallow high-resolution 3D velocity model that can be used in the simulation of strong ground motion and for evaluating potential seismic hazards.

In this work, we combine the CALYPSO method with DFT calculations to conduct a comprehensive structural search of Ta2Bn (n = 10 ∼ 20) clusters. Among all the candidate structures obtained by CALYPSO searching, the structures of ground state Ta2Bn clusters at each size are determined according to their total energy and symmetry. The relative stability analysis indicates that the ground state Ta2B16 and Ta2B18 clusters with the unique bicyclic boron ring and two Ta atoms as axes exhibit excellent stability in the studied range, with their HOMO-LUMO gaps of 2.374 and 2.640 eV, respectively. The bonding analyses reveal that the strong interaction between two Ta atoms and the outer B16/18 bicyclic ring dominates their significant stability, especially the interaction between Ta-d AOs and B-s/p AOs. It is confirmed that both Ta2B16 and Ta2B18 have strong aromaticity by examining the isochemical shielding surface (ICSS). Finally, the strong coupling between their outer boron rings (B16/18) and two Ta atoms inside the structures of Ta2B16 and Ta2B18 is further elucidated by the electronic absorption spectrum (UV–vis and CTS).

Vascular smooth muscle cells (VSMCs) are critical elements of the vascular wall and play a crucial role in the genesis and development of atherosclerosis (AS). Increasingly, studies have indicated that long noncoding RNAs (lncRNAs) regulate VSMC proliferation, apoptosis, and other biological processes. Nevertheless, the role of lncRNA NFIA-AS1 (hereinafter referred to as NFIA-AS1) in VSMCs and AS remains unclear. Quantitative real-time PCR (qRT-PCR) was performed to analyze the messenger RNA (mRNA) levels of NFIA-AS1 and miR-125a-3p. CCK-8 and EdU staining were performed to detect VSMC proliferation. VSMC apoptosis was evaluated by flow cytometry. The expression of various proteins was detected using western blotting. The levels of inflammatory cytokines secreted by VSMCs were measured by enzyme linked immunosorbent assay (ELISA). The binding sites of NFIA-AS1 and miR-125a-3p, as well as miR-125a-3p and AKT1, were analyzed using bioinformatics methods and validated using a luciferase reporter assay. The function of NFIA-AS1/miR-125a-3p/AKT1 in VSMCs was clarified through loss- and gain-of-functional experiments. We confirmed that NFIA-AS1 was highly expressed in AS tissues and VSMCs induced by oxidized low-density lipoprotein (Ox-LDL). Knockdown of NFIA-AS1 restrained the exceptional growth of Ox-LDL-induced VSMCs, promoted their apoptosis, and decreased the secretion of inflammatory factors and expression of adhesion factors. In addition, NFIA-AS1 regulated the proliferation, apoptosis, and inflammatory response of VSMCs through the miR-125a-3p/AKT1 axis, suggesting that NFIA-AS1 may be a potential therapeutic target for AS.

ObjectiveThis study aimed to investigate the feasibility of using indocyanine green (ICG) near-infrared (NIR) imaging during lymphadenectomy for oesophageal cancer.MethodsEighty-seven patients with primary oesophageal cancer were enrolled in this study. All the enrolled patients received an endoscopic injection of ICG between 40 min and 23 h before surgery. Nodal dissection during surgery was performed under fluorescence imaging visualisation, with the NIR signal shown in purple. ICG+ or ICG− nodes were recorded station by station and were microscopically evaluated.ResultsEndoscopic peritumoral ICG injection was successfully performed in all patients. Major post-surgery complications included wound infection, pleural effusion, dysphonia, pneumonia and anastomotic fistula. No patients experienced ICG-related adverse events. A total of 2,584 lymph nodes were removed, and the mean number of lymph nodes for each patient was 29.70 ± 9.24. Most of the removed nodes (97.83%) were ICG+, and 3.32% of the ICG+ nodes were metastatic. No metastatic nodes were ICG− or belonged to an ICG− lymph node station. The time from ICG injection to surgery did not affect the number of harvested lymph nodes.ConclusionsThe use of ICG-NIR imaging during oesophageal cancer surgery can enhance the visualisation of lymph nodes during surgery. It is a feasible, safe and helpful technique for lymphadenectomy.

BackgroundThe relationship between sarcopenia and surgery has attracted an increasing number of researchers in recent years. Our study aimed to identify the current research hotspot and status in this field by using bibliometric and visualization analysis.MethodsPublications about the relationship between sarcopenia and surgery that met the inclusion criteria were collected from the Science Citation Index Expanded. The bibliometric and visualized studies were performed using VOSviewer, and R.ResultsA total of 2,261 documents on the relationship between sarcopenia and surgery were included in our study. These articles were written by 13,757 authors from 2,703 institutions in 70 countries and were published in 772 journals. The USA is the most productive and influential country in this field (524 publications and 15,220 citations). The Udice French Research Universities was the most productive institution in this field (57 publications), and the University of Alberta had the largest number of citations. Annuals of Surgical Oncology published the most studies in this field. Shen Xian was the most productive author in this field (number of publications = 19), and Baracos Vickie was the most influential author, whose studies in this field had been cited 2,209 times. The cluster analysis was performed and visualized, and the keywords were classified into 6 clusters: Cluster 1 (body composition and nutrition), Cluster 2 (sarcopenia), Cluster 3 (malnutrition and cachexia), Cluster 4 (cancer surgery), Cluster 5 (elderly and frailty), Cluster 6 (neuromuscular scoliosis).ConclusionThe relationship between sarcopenia and surgery was still a controversial and well-discussed topic in recent years. Our study showed that the study in this field mainly focused on sarcopenia, oncology surgery, orthopedics, and nutrition.

Fourier transform infrared spectroscopy (FTIR) is widely used in gas detection of SF6 decomposition components. A gas cell is an important element in the detection system, which can directly affect the accuracy and sensitivity of detection. During the long-term use of the gas cell, SF6 decomposition components may be adsorbed on the inner wall of the gas cell, which affects the detection results and the life of the gas cell. Therefore, the study on the adsorption between the gas cell material and the SF6 decomposition component is of great significance for improving the accuracy of detection. In this paper, based on the density functional theory, the adsorption process and adsorption degree of SF6 decomposition components (SOF2, SO2F2, CO, SO2, and H2S) with three typical main gas cell materials (Al, Cu, and Fe) and two gas cell coating materials (Teflon and Au) were simulated. It was found that the adsorption of Teflon and Au with gas was weak in the five materials and that of Teflon was the weakest. The adsorption energy of the three main gas cell materials was 2.65–6.31 times that of Teflon. The simulation results were also verified by FTIR and the GC-Materials Studio (MS) method. FTIR results showed that Teflon and Au had the weakest influence on the infrared spectral absorption peak and the effect of the two materials on SOF2 and SO2F2 gas absorption peaks is only less than 0.1. The results of gas chromatograph-mass spectrometer (GC-MS) showed that the effects of Teflon materials and Au on gas concentration were 2%–9.41% and the effects of Cu, Fe, and Al on gas concentration were 4.48%–65.43%. Therefore, Au and Teflon are suitable as coating materials for gas cells, which can reduce the adsorption of gas and improve the accuracy of infrared spectroscopy measurement. The results of this paper provide a reference for the development of application of optical gas detection technology in SF6 decomposition component detection.

In order to achieve specific enrichment of target glycoproteins, double molecular recognition ligands functionalized surface solid-phase adsorption materials that can play a role under physiological pH conditions, have obvious advantages. In this work, a novel strategy was proposed for the synthesis of double molecular recognition functionalized magnetic graphene nanocomposites. Horseradish peroxidase was selected as the template proteins for evaluating the selectivity and binding capacity of the adsorption material. The bimolecular recognition was realized by introducing 4-carboxyphenylboronic acid (CPBA) and Suberic acid bis(3-sulfo-N-hydroxysuccinimide ester) sodium salt (Sulfo-DSS) as functional ligands. The abundant oxygen-containing groups in the complex (abbreviated as CPDS/CMCS/Fe3O4-rGO) were beneficial to reduce the pKa value of CPBA. Finally, CPDS/CMCS/Fe3O4-rGO realized the selective adsorption of glycoproteins in the neutral environment (pH 7.0). The resultant CPDS/CMCS/Fe3O4-rGO exhibited a high adsorption capacity of 1280.6 mg g−1 and excellent specificity toward glycoproteins compared to nonglycoproteins. Moreover, CPDS/CMCS/Fe3O4-rGO with strong magnetic responses (59.29 emu·g−1), could achieve rapid aggregation and separation under the external magnetic field. The results demonstrated the great potential of CPDS/CMCS/Fe3O4-rGO composites to separate and enrich glycoproteins from the complex biological sample for the glycoproteins analysis.

U-Mo alloys were considered to be the most promising candidates for high-density nuclear fuel. The uniaxial tensile behavior of nanocrystalline U-10Mo alloys with average grain sizes of 8–23 nm was systematically studied by molecular dynamics (MD) simulation, mainly focusing on the influence of average grain size on the mechanical properties and deformation mechanisms. The results show that Young’s modulus, yield strength and ultimate tensile strength follow as average grain size increases. During the deformation process, localized phase transitions were observed in samples. Grain boundary sliding and grain rotation, as well as twinning, dominated the deformation in the smaller and larger grain sizes samples, respectively. Increased grain size led to greater localized shear deformation, resulting in greater stress drop. Additionally, we elucidated the effects of temperature and strain rate on tensile behavior and found that lower temperatures and higher strain rates not only facilitated the twinning tendency but also favored the occurrence of phase transitions in samples. Results from this research could provide guidance for the design and optimization of U-10Mo alloys materials.

We previously found that inhibition of p66Shc confers protection against hepatic stellate cell (HSC) activation during liver fibrosis. However, the effect of p66Shc on HSC proliferation, as well as the mechanism by which p66Shc is modulated, remains unknown. Here, we elucidated the effect of p66Shc on HSC proliferation and evaluated microRNA (miRNA)-p66Shc-mediated reactive oxidative species (ROS) generation in liver fibrosis. An in vivo model of carbon tetrachloride (CCl4)-induced liver fibrosis in rats and an LX-2 cell model were developed. p66Shc expression was significantly upregulated in rats with CCl4-induced liver fibrosis and in human fibrotic livers. Additionally, p66Shc knockdown in vitro attenuated mitochondrial ROS generation and HSC proliferation. Interestingly, p66Shc promoted HSC proliferation via β-catenin dephosphorylation in vitro. MicroRNA (miR)-203a-3p, which was identified by microarray and bioinformatics analyses, directly inhibited p66Shc translation and attenuated HSC proliferation in vitro. Importantly, p66Shc was found to play an indispensable role in the protective effect of miR-203a-3p. Furthermore, carnosic acid (CA), the major antioxidant compound extracted from rosemary leaves, protected against CCl4-induced liver fibrosis through the miR-203a-3p/p66Shc axis. Collectively, these results suggest that p66Shc, which is directly suppressed by miR-203a-3p, is a key regulator of liver fibrosis. This finding may lead to the development of therapeutic targets for liver fibrosis.

Fatty acid β-oxidation is an essential pathogenic mechanism in nonalcoholic fatty liver disease (NAFLD), and TATA-box binding protein associated factor 9 (TAF9) has been reported to be involved in the regulation of fatty acid β-oxidation. However, the function of TAF9 in NAFLD, as well as the mechanism by which TAF9 is regulated, remains unclear. In this study, we aimed to investigate the signaling mechanism underlying the involvement of TAF9 in NAFLD and the protective effect of the natural phenolic compound Danshensu (DSS) against NAFLD via the HDAC1/TAF9 pathway. An in vivo model of high-fat diet (HFD)-induced NAFLD and a palmitic acid (PA)-treated AML-12 cell model were developed. Pharmacological treatment with DSS significantly increased fatty acid β-oxidation and reduced lipid droplet (LD) accumulation in NAFLD. TAF9 overexpression had the same effects on these processes both in vivo and in vitro. Interestingly, the protective effect of DSS was markedly blocked by TAF9 knockdown. Mechanistically, TAF9 was shown to be deacetylated by HDAC1, which regulates the capacity of TAF9 to mediate fatty acid β-oxidation and LD accumulation during NAFLD. In conclusion, TAF9 is a key regulator in the treatment of NAFLD that acts by increasing fatty acid β-oxidation and reducing LD accumulation, and DSS confers protection against NAFLD through the HDAC1/TAF9 pathway.

BackgroundParathyroid carcinoma (PC) is a rare malignancy, the incidence of which is less than 1/1 million per year. Sarcomatoid parathyroid carcinoma (SaPC) is an extremely peculiar subtype; only three cases have been reported internationally. It consists of both malignant epithelial components and sarcomatoid components (mesenchymal origin) simultaneously. This “confusing” cancer exhibits higher invasiveness, and traditional surgery does not appear to achieve the expectation, which differs significantly from that of general PC.ObjectiveTo characterize the clinicopathologic features of SaPC and explore similarities and differences between SaPC and general PC.Materials and MethodsWe collected clinical data of SaPC cases from our center and literature. The SaPC case in our center was presented. To better understand the characteristics of SaPC, we also reviewed clinical information in general PC cases from our center and literature within the last 5 years, and a systematic review was performed for further comparison.ResultsA 60-year-old woman was admitted for a neck mass and hoarseness. After the surgery, she was confirmed as SaPC and ultimately developed local recurrence at 3 months. Together with the reported cases from literature, four cases of SaPC (three cases from literature) and 203 cases of general PC (200 cases from literature) were reviewed. Both tumors showed obvious abnormalities in parathormone (PTH) level and gland size. Compared to general PC, SaPC has a later age of onset (60.50 ± 7.42 vs. 51.50 ± 8.29), relatively low levels of PTH (110.28 ± 59.32 vs. 1,156.07 ± 858.18), and a larger tumor size (6.00 ± 1.63 vs. 3.14 ± 0.70). For SaPC, all four cases were initially misdiagnosed as thyroid tumors (4/4). Spindle cell areas or transitional zones were common pathological features in SaPC cases (3/4).ConclusionSaPC is a very rare pathologic subtype of PC and appears to be much more easily misdiagnosed as a thyroid tumor. Spindle cell areas or transitional zones are highly possible to be pathological features in its sarcomatoid components. Despite many similarities, there are some differences between SaPC and general PC—SaPC does not show the obvious endocrine feature but stronger aggressiveness. Surgical treatment of SaPC does relieve life-threatening symptoms and improve quality of life even with recurrence in the short term.

Pyroptosis is a newly discovered form of cell death. Peroxiredoxin 3 (PRX3) plays a crucial role in scavenging reactive oxygen species (ROS), but its hepatoprotective capacity in acetaminophen (APAP)-induced liver disease remains unclear. The aim of this study was to assess the role of PRX3 in the regulation of pyroptosis during APAP-mediated hepatotoxicity. We demonstrated that pyroptosis occurs in APAP-induced liver injury accompanied by intense oxidative stress and inflammation, and liver specific PRX3 silencing aggravated the initiation of pyroptosis and liver injury after APAP intervention. Notably, excessive mitochondrial ROS (mtROS) was observed to trigger pyroptosis by activating the NLRP3 inflammasome, which was ameliorated by Mito-TEMPO treatment, indicating that the anti-pyroptotic role of PRX3 relies on its powerful ability to regulate mtROS. Overall, PRX3 regulates NLRP3-dependent pyroptosis in APAP-induced liver injury by targeting mitochondrial oxidative stress.

High-resolution imaging of fault zone structure and its temporal changes can not only advance our understanding of earthquake physics, but is also critical for better seismic hazard preparation and mitigation. In the past a few years, we deployed multi-scale dense arrays across the Chenghai fault system in Binchuan, Yunnan, China. The first array consisted of 381 intermediate-period three-component seismometers with an average station spacing of ∼2 ​km. The array has been deployed in the field for ∼3 months in 2017 and recorded numerous local and teleseismic earthquakes. Travel time analyses based on teleseismic earthquakes and an airgun source in the region indicated clear signature of low-velocity fault zones in the southern branch of the Chenghai fault system. In 2018 we deployed two other linear arrays using the same instruments with much smaller inter-station spacing, e.g. 30–50 ​m, across the southern branch the Chenghai fault. The profile lengths were 8 and 5 ​km, respectively. Record sections of the airgun source on the two linear arrays clearly marked a low-velocity zone (LVZ) within the southern array but no such signature in the northern array, suggesting along-strike variation of the LVZ. Although the instruments within our dense arrays had an intermediate frequency band, we demonstrated that they were capable of characterizing crustal structure with techniques commonly applied to broadband signals such as receiver functions. To our best knowledge, this was the first time to have multi-scale across-fault dense arrays with three-component seismometers in such apertures. These results lay out the pavement to comprehensively investigate fault zone structures as well as to derive subsurface structural changes using dense arrays and the airgun source.

Purpose. To analyze the epidemiological characteristics of inpatients who underwent surgery for glaucoma at Tianjin Eye Hospital from 2013 to 2017. Methods. All glaucoma inpatients who underwent surgery at Tianjin Eye Hospital from 2013 to 2017 were evaluated. The relationships of age and sex with different types of glaucoma were analyzed. The differences in the prevalence and family history of glaucoma among patients with different systemic diseases were compared. Additionally, the effects of different surgical methods for primary angle-closure glaucoma (PACG) and primary open-angle glaucoma (POAG) were compared. Results. A total of 4539 patients with glaucoma were retrospectively analyzed. The most prevalent type was PACG (60.15%), followed by secondary glaucoma (SG, 25.53%), POAG (7.6%), uncontrollable intraocular pressure (IOP) after antiglaucoma surgery (4.71%), mixed glaucoma (MG, 10%), and congenital glaucoma (CG, 0.9%). The main surgical methods were phacoemulsification (phaco), phacotrabeculectomy (phaco-trab), and trabeculectomy (trab). The rate of phaco-trab increased, while that of trab decreased. The proportion of women in the PACG group was higher than those in the POAG and SG groups, and there was a pronounced tendency for family clustering (P

Background: Hydrogen peroxide (H2O2)-induced mitochondrial oxidative damage is critical to intestinal ischemia/reperfusion (I/R) injury, and PRDX3 is an efficient H2O2 scavenger that protects cells from mitochondrial oxidative damage and apoptosis. However, the function of PRDX3 in intestinal I/R injury is unclear. The aim of this study was to investigate the precise mechanism underlying the involvement of PRDX3 in intestinal I/R injury. Methods: An intestinal I/R model was established in mice with superior mesenteric artery occlusion, and Caco-2 cells were subjected to hypoxia/reoxygenation (H/R) for the in vivo simulation of I/R. Results: PRDX3 expression was decreased during intestinal I/R injury, and PRDX3 overexpression significantly attenuated H/R-induced mitochondrial oxidative damage and apoptosis in Caco-2 cells. The level of acetylated PRDX3 was clearly increased both in vivo and in vitro. The inhibition of SIRTs by nicotinamide (NAM) increased the level of acetylated PRDX3 and impaired the antioxidative activity of PRDX3. Furthermore, NAM did not increase the acetylation of PRDX3 in sirtuin-3 (SIRT3)-knockdown Caco-2 cells. Importantly, PRDX3 acetylation was increased in mice lacking SIRT3, and this effect was accompanied by serious mitochondrial oxidative damage, apoptosis and remote organ damage after intestinal I/R injury. We screened potential sites of PRDX3 acetylation in the previously reported acetylproteome through immunoprecipitation (IP) experiments and found that SIRT3 deacetylates K253 on PRDX3 in Caco-2 cells. Furthermore, PRDX3 with the lysine residue K253 mutated to arginine (K253R) increased its dimerization in Caco-2 cells after subjected to 12 h hypoxia and followed 4 h reoxygenation. Caco-2 cells transfected with the K253R plasmid exhibited notably less mitochondrial damage and apoptosis, and transfection of the K253Q plasmid abolished the protective effect of PRDX3 overexpression. Analysis of ischemic intestines from clinical patients further verified the correlation between SIRT3 and PRDX3. Conclusions: PRDX3 is a key protective factor for intestinal I/R injury, and SIRT3-mediated PRDX3 deacetylation can alleviate intestinal I/R-induced mitochondrial oxidative damage and apoptosis. Keywords: PRDX3, SIRT3, Mitochondrial oxidative damage, Apoptosis, Intestinal ischemia reperfusion

Background/Aims: Ischemic postconditioning (iPoC) represents a promising strategy to mitigate ischemia/reperfusion (I/R) injury of the intestine, yet the mechanisms of this treatment remain to be elucidated. Circular RNAs (circRNAs), a novel class of endogenous non-coding RNAs, have recently been recognized as important regulators of gene expression and pathological processes. Here, we aimed to investigate the expression patterns of circRNAs after intestinal I/R with and without iPoC and, furthermore, to explore the potential mechanisms of iPoC in relation to the differentially expressed circRNAs. Methods: The global circRNA and mRNA expression profiles in mouse intestinal mucosa were initially screened by microarray (n = 3 per group) and quantitative real-time PCR was used to validate the expression pattern of circRNAs and mRNAs. Bioinformatics analysis including Gene ontology, KEGG pathway analysis, microRNA binding sites identification and circRNA-miRNA-mRNA network construction were utilized for in-depth mechanism exploration. Results: There were 4 up- and 58 downregulated circRNAs as well as 322 up- and 199 downregulated mRNAs in the intestinal I/R group compared with the sham group, whereas compared with I/R, iPoC treatment significantly upregulated 12 circRNAs and 129 mRNAs and downregulated 21 circRNAs and 174 mRNAs. The expression levels of a randomly selected set of 6 circRNAs and 5 mRNAs were successfully validated by qRT-PCR. Through a systematic comparison of the direction of circRNA expression changes in all groups, we identified two circRNAs, circRNA_012412 and circRNA_016863, that may be closely associated with the protective mechanisms of iPoC. Finally, four possible circRNA_012412/circRNA_016863-miRNA-mRNA pathways were predicted, which may play important roles in endogenous protective signaling in iPoC. Conclusions: This study was the first to comprehensively delineate the expression profiles of circRNAs in a mouse model of intestinal I/R and iPoC and provides novel clues for understanding the mechanisms of iPoC against intestinal I/R injury.

As a relatively new method of processing non-stationary signal with high time-frequency resolution, S transform can be used to analyze the time-frequency characteristics of seismic signals. It has the following characteristics: its time-frequency resolution corresponding to the signal frequency, reversible inverse transform, basic wavelet that does not have to meet the permit conditions. We combined the threshold method, proposed the S-transform threshold filtering on the basis of S transform time-frequency filtering, and processed airgun seismic records from temporary stations in “Yangtze Program” (the Anhui experiment). Compared with the results of the bandpass filtering, the S transform threshold filtering can improve the signal to noise ratio (SNR) of seismic waves and provide effective help for first arrival pickup and accurate travel time. The first arrival wave seismic phase can be traced farther continuously, and the Pm seismic phase in the subsequent zone is also highlighted. Keywords: S transform, Time-frequency filtering, Airgun data, Threshold filtering, De-noising

Molecular dynamics simulations were performed to investigate the uniaxial tensile properties of nanocrystalline U0.5Th0.5O2 solid solution with the Born–Mayer–Huggins potential. The results indicated that the elastic modulus increased linearly with the density relative to a single crystal, but decreased with increasing temperature. The simulated nanocrystalline U0.5Th0.5O2 exhibited a breakdown in the Hall–Petch relation with mean grain size varying from 3.0 nm to 18.0 nm. Moreover, the elastic modulus of U1-yThyO2 solid solutions with different content of thorium at 300 K was also studied and the results accorded well with the experimental data available in the literature. In addition, the fracture mode of nanocrystalline U0.5Th0.5O2 was inclined to be ductile because the fracture behavior was preceded by some moderate amount of plastic deformation, which is different from what has been seen earlier in simulations of pure UO2.

Background: Endoplasmic reticulum stress (ER stress) plays a critical role in the pathogenesis of liver fibrosis; thus, it can be a potential therapeutic target of fibrosis. However, the mechanism of ER stress regulation in fibrosis, particularly through sirtuin 1 (SIRT1), remains unclear. The objective of this study was to investigate the effect of SIRT1-mediated inhibition of ER stress in bile duct ligation (BDL)-induced liver fibrosis, and to explore the effect of salvianolic acid A (SalA) on BDL-induced liver fibrosis through SIRT1/heat shock factor 1 (HSF1) signaling.Materials and Methods: We explored the effects of SalA on liver fibrosis and ER stress in BDL-induced liver fibrosis in rats and the human hepatic stellate cell line LX2 cells. The LX2 cells were treated with 20 ng of platelet-derived growth factor-BB homodimer (PDGF-BB) for 24 h, and then incubated in the absence or presence of SalA (25 μM) for 24 h.Results:In vivo, SalA treatment alleviated BDL-induced liver injury and ER stress. Importantly, SalA treatment increased HSF1 expression and activity using a SIRT1-dependent mechanism. In LX2 cells, PDGF-BB induced ER stress and fibrosis were blocked by HSF1 overexpression. Furthermore, SIRT1 siRNA abrogated the SalA-mediated promotion of HSF1 deacetylation and expression, suggesting that SalA-mediated protection occurs by SIRT1 targeting HSF1 for deacetylation.Conclusion: This is the first study to identify the SIRT1/HSF1 pathway as a key therapeutic target for controlling BDL-induced liver fibrosis and to show that SalA confers protection against BDL- and PDGF-BB-induced hepatic fibrosis and ER stress through SIRT1-mediated HSF1 deacetylation.

Hydrogen-induced disproportionation (HID) during the cycles of absorption and desorption leads to a serious decline in the storage capacity of the ZrCo alloy, which has been recognized as the biggest obstacle to its application. Therefore, the prerequisite of a ZrCo application is to solve its anti-disproportionation problem in the field of rapid hydrogen isotope storage. Beyond surface modification and nanoball milling, this work systematically reviews the method of element substitution, which can obviously improve the anti-disproportionation. From a micro angle, as hydrogen atoms that occupy the 8e site in the ZrCoH3 lattice are instable and are considered to be the driving force of disproportionation, researchers believe that element substitution by changing the occupation of hydrogen atoms at the 8e site can improve the anti-disproportionation of the alloy. At present, Ti/Nb substitutions for the Zr terminal among substitute elements have an excellent anti-disproportionation performance. In this work, up-to-date research studies on anti-disproportionation and its disproportionation mechanism of the ZrCo alloy are introduced by combining experiments and simulations. Moreover, the optimization of the alloy based on the occupation mechanism of 8e sites is expected to improve the anti-disproportionation of the ZrCo alloy.

Fibrosis reflects a progression to liver cancer or cirrhosis of the liver. Recent studies have shown that high-mobility group box-1 (HMGB1) plays a major role in hepatic injury and fibrosis. Carnosic acid (CA), a compound extracted from rosemary, has been reported to alleviate alcoholic and non-alcoholic fatty liver injury. CA can also alleviate renal fibrosis. We hypothesized that CA might exert anti-liver fibrosis properties through an HMGB1-related pathway, and the results of the present study showed that CA treatment significantly protected against hepatic fibrosis in a bile duct ligation (BDL) rat model. CA reduced the liver expression of α-smooth muscle actin (α-SMA) and collagen 1 (Col-1). Importantly, we found that CA ameliorated the increase in HMGB1 and Toll-like receptor 4 (TLR4) caused by BDL, and inhibited NF-κB p65 nuclear translocation in fibrotic livers. In vitro, CA inhibited LX2 cell activation by inhibiting HMGB1/TLR4 signaling pathway. Furthermore, miR-29b-3p decreased HMGB1 expression, and a dual-luciferase assay validated these results. Moreover, CA down-regulated HMGB1 and inhibited LX2 cell activation, and these effects were significantly counteracted by antago-miR-29b-3p, indicating that the CA-mediated inhibition of HMGB1 expression might be miR-29b-3p dependent. Collectively, the results demonstrate that a miR-29b-3p/HMGB1/TLR4/NF-κB signaling pathway, which can be modulated by CA, is important in liver fibrosis, and indicate that CA might be a prospective therapeutic drug for liver fibrosis.

This study was conducted to investigate the effects of soil water deficit on insecticidal protein expression in boll shells of cotton transgenic for a Bt gene. In 2014, Bt cotton cultivars Sikang 1 (a conventional cultivar) and Sikang 3 (a hybrid cultivar) were planted in pots and five soil water content treatments were imposed at peak boll stage: 15% (G1), 35% (G2), 40% (G3), 60% (G4), and 75% field capacity (CK), respectively. Four treatments (G2, G3, G4, and CK) were repeated in 2015 in the field. Results showed that the insecticidal protein content of boll shells decreased with increasing water deficit. Compared with CK, boll shell insecticidal protein content decreased significantly when soil water content was below 60% of maximum water holding capacity for Sikang 1 and Sikang 3. However, increased Bt gene expression was observed when boll shell insecticidal protein content was significantly reduced. Activity assays of key enzymes in nitrogen metabolism showed that boll shell protease and peptidase increased but nitrogen reductase and glutamic-pyruvic transaminase (GPT) decreased. Insecticidal protein content exhibited significant positive correlation with nitrogen reductase and GPT activities; and significant negative correlation with protease and peptidase activities. These findings suggest that the decrease of insecticidal protein content associated with increasing water deficit was a net result of decreased synthesis and increased decomposition.

Background/Aims: MicroRNAs (miRNAs) have a key role in carcinogenesis and cancer development, but the role of miRNAs in the progression of esophageal cancer (EC) remains unclear. Methods: The TE-1 and Eca-109 EC cell lines were used. The expression of miR-491 and candidate gene TPX2 in EC samples (n=99) were detected by RT-PCR. The cells invasive ability was determined by transwell assay. The luciferase reporter assay was used to confirm the regulation mechanism. Results: A decreased expression of miR-491 was detected in the EC clinical samples compared with the corresponding adjacent tumor tissues. Aberrant expression of miR-491 regulated cells invasion and EMT markers. Furthermore, we verified that TPX2 was a target gene of miR-491. Conclusions: miR-491 may play a critical role in EC.

Acetaminophen (APAP) is used drugs worldwide for treating pain and fever. However, APAP overdose is the principal cause of acute liver failure in Western countries. Salvianolic acid B (SalB), a major water-soluble compound extracted from Radix Salvia miltiorrhiza, has well-known antioxidant and anti-inflammatory actions. We aimed to evaluate the ability of SalB to protect against APAP-induced acute hepatotoxicity by inducing nuclear factor-erythroid-2-related factor 2 (Nrf2) expression. SalB pretreatment ameliorated acute liver injury caused by APAP, as indicated by blood aspartate transaminase levels and histological findings. Moreover, SalB pretreatment increased the expression of Nrf2, Heme oxygenase-1 (HO-1) and glutamate-l-cysteine ligase catalytic subunit (GCLC). Furthermore, the HO-1 inhibitor zinc protoporphyrin and the GCLC inhibitor buthionine sulfoximine reversed the protective effect of SalB. Additionally, siRNA-mediated depletion of Nrf2 reduced the induction of HO-1 and GCLC by SalB, and SalB pretreatment activated the phosphatidylinositol-3-kinase (PI3K) and protein kinase C (PKC) signaling pathways. Both inhibitors (PI3K and PKC) blocked the protective effect of SalB against APAP-induced cell death, abolishing the SalB-induced Nrf2 activation and decreasing HO-1 and GCLC expression. These results indicated that SalB induces Nrf2, HO-1 and GCLC expression via activation of the PI3K and PKC pathways, thereby protecting against APAP-induced liver injury.

Intestinal ischemia-reperfusion (I/R) injury is a serious clinical pathophysiological process that may result in acute local intestine and remote liver injury. Protocatechuic acid (PCA), which has been widely studied as a polyphenolic compound, induces expression of antioxidative genes that combat oxidative stress and cell apoptosis. In this study, we investigated the effect of PCA pretreatment for protecting intestinal I/R-induced local intestine and remote liver injury in mice. Intestinal I/R was established by superior mesenteric artery occlusion for 45 min followed by reperfusion for 90 min. After the reperfusion period, PCA pretreatment markedly alleviated intestine and liver injury induced by intestinal I/R as indicated by histological alterations, decreases in serological damage parameters and nuclear factor-kappa B and phospho-foxo3a protein expression levels, and increases in glutathione, glutathione peroxidase, manganese superoxide dismutase protein expression, and Bcl-xL protein expression in the intestine and liver. These parameters were accompanied by PCA-induced adaptor protein p66shc suppression. These results suggest that PCA has a significant protective effect in the intestine and liver following injury induced by intestinal I/R. The protective effect of PCA may be attributed to the suppression of p66shc and the regulation of p66shc-related antioxidative and antiapoptotic factors.

Deformation mechanisms of the nanocrystalline body-centered cubic U-Mo alloy were investigated through molecular dynamics simulations, focusing on the influences of the grain size and Mo content. Strain-hardening behavior was only observed under small grain sizes. GB-mediated processes and grain rotation played an important part in the deformation of small-sized grains. Grain rotation competed against twinning in the superplastic area while the combination of twinning and grain rotation could promote merging between the grains. The heterogeneous and homogeneous mechanisms of microtwin nucleation were observed. In the small grain-sized system, twins were formed by the continuous emission of Shockley partials from the grain boundaries onto adjacent slip planes. Moreover, two additional twin nucleation mechanisms (including grain boundary splitting and dynamical overlap of the stacking faults) were also identified in larger-sized grains. Twin-GB interactions may lead to the generation of new twins. The increased Mo content in the U-Mo alloy could not only stabilize the bcc phase of γ-U but also promote grain rotation and coalescence. At ambient temperature, stress-induced phase transitions from bodycentered cubic (bcc) to face-centered cubic (fcc) and hexagonal close-packed (hcp) structures appeared locally, and the fcc and hcp phase transitions were reversible and irreversible for the applied stress, respectively. [ABSTRACT FROM AUTHOR]