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Objective To prevent water leakage issues in large-diameter shield tunnel, ensure high-speed train operational safety and normal tunnel functionality, it is necessary to carry out analysis and research on tunnel segment joint deformation and waterproof performance under high-speed train vibration. Method Relying on the Zhanjiang Bay Subsea Tunnel project, a soil-tunnel three-dimensional model and a sealing gasket-groove two-dimensional refined model are established using finite element software. First, the dynamics response and deformation characteristics of segment joints under high-speed train vibration in large-diameter shield tunnel are studied, with longitudinal joints as example. Then, the waterproof performance of a sealing gasket is analyzed based on the most adverse joint deformation working condition. Result & Conclusion The research results indicate that under the vibration of a single high-speed train, the displacement response process of segment joints can be divided into three stages: deformation increase, deformation being danger, and deformation decline. During the second stage, significant joint opening and misalignment occur at the upper part and both ends of the segment ring, while adjacent joints experience reduced opening and misalignment due to compression from both adjacent side segments. There is almost no deformation at the joints below the track bed, as the tunnel track bed significantly mitigates the impact of train vibration on segment linings. The contact stress between sealing gaskets follows a U-shaped distribution, decreasing from the central contact area towards both edges between the sealing gasket and the segment groove. Leakage is more likely to occur at the contact surfaces between the sealing gaskets than along the contact path between the sealing gasket and the segment groove. Under the most adverse working condition of this project, a provided triangular perforated sealing gasket is found to meet the tunnel waterproof requirements.

Arteriovenous fistula (AVF) is currently the preferred vascular access for hemodialysis patients. However, the low maturation rate of AVF severely affects its use in patients. A more comprehensive understanding and study of the mechanisms of AVF maturation is urgently needed. In this study, we downloaded the publicly available datasets (GSE119296 and GSE220796) from the Gene Expression Omnibus (GEO) and merged them for subsequent analysis. We screened 84 differentially expressed genes (DEGs) and performed the functional enrichment analysis. Next, we integrated the results obtained from the degree algorithm provided by the Cytohubba plug-in, Molecular complex detection (MCODE) plug-in, weighted gene correlation network analysis (WGCNA), and Least absolute shrinkage and selection operator (LASSO) logistic regression. This integration allowed us to identify CTSG as a hub gene associated with AVF maturation. Through the literature search and Pearson's correlation analysis, the genes matrix metalloproteinase 2 (MMP2) and MMP9 were identified as potential downstream effectors of CTSG. We then collected three immature clinical AVF vein samples and three mature samples and validated the expression of CTSG using immunohistochemistry (IHC) and double-immunofluorescence staining. The IHC results demonstrated a significant decrease in CTSG expression levels in the immature AVF vein samples compared to the mature samples. The results of double-immunofluorescence staining revealed that CTSG was expressed in both the intima and media of AVF veins. Moreover, the expression of CTSG in vascular smooth muscle cells (VSMCs) was significantly higher in the mature samples compared to the immature samples. The results of Masson's trichrome and collagen I IHC staining demonstrated a higher extent of collagen deposition in the media of immature AVF veins compared to the mature. By constructing an in vitro CTSG overexpression model in VSMCs, we found that CTSG upregulated the expression of MMP2 and MMP9 while downregulating the expression of collagen I and collagen III. Furthermore, CTSG was found to inhibit VSMC migration. CTSG may promote AVF maturation by stimulating the secretion of MMP2 and MMP9 from VSMCs and reducing the extent of medial fibrosis in AVF veins by inhibiting the secretion of collagen I and collagen III. [ABSTRACT FROM AUTHOR]

Background and Aim: Fexuprazan is a novel potassium‐competitive acid blocker (P‐CAB). This study aimed to explore the noninferior efficacy and safety of fexuprazan to esomeprazole in treating erosive esophagitis (EE). Methods: This was a phase III, randomized, double‐blind multicenter study. Patients with endoscopically confirmed EE were randomized to receive fexuprazan 40 mg or esomeprazole 40 mg once a daily for 4–8 weeks. The healing rates of EE, symptom response, GERD‐health‐related quality life (GERD‐HRQL), and treatment‐emergent adverse events (TEAEs) were compared between fexuprazan group and esomeprazole group. Results: A total of 332 subjects were included in full analysis set (FAS) and 311 in per‐protocol set (PPS). The healing rates of fexuprazan and esomeprazole groups at 8 weeks were 88.5% (146/165) and 89.0% (145/163), respectively, in FAS and 97.3% (145/149) and 97.9% (143/146), respectively, in PPS. Noninferiority of fexuprazan compared with esomeprazole according to EE healing rates at 8 weeks was demonstrated in both FAS and PPS analysis. No significant difference was found between groups in EE healing rates at 4 weeks, symptom responses, and changes of GERD‐HRQL. The incidence of drug‐related AEs was 19.4% (32/165) in fexuprazan arm and 19.6% (32/163) in esomeprazole arm. Conclusion: This study demonstrated noninferior efficacy of fexuprazan to esomeprazole in treating EE. The incidence of TEAEs was similar between fexuprazan and esomeprazole. Trial registration number NCT05813561. [ABSTRACT FROM AUTHOR]

The Sand River area is in the northeastern part of the Central Zone (CZ) of the Limpopo Belt, and represents a key terrane to reveal early Precambrian tectonic processes in southern Africa. Based on petrology, U–Pb zircon ages, and major and trace element data of high-pressure (HP) mafic granulites from the Sand River area, the tectonic evolution of the Central Zone of the Limpopo Belt is re-evaluated here that allows revision of previous interpretations. The protoliths of the HP mafic granulites and amphibolites are sub-alkaline tholeiitic basalts similar to those formed at a mid-ocean ridge and intruded at 2.8 Ga. Based on the distinct mineral assemblages, three metamorphic stages (M1–M3) are recognized in the studied samples: (1) a peak HP granulite facies stage M1 (~1.17–1.32 GPa/~825–870°C), (2) a post-peak near-isothermal decompression stage M2 (~0.70–0.73 GPa/~835–880°C), and (3) a later, independent metamorphic stage M3 (~0.53–0.69 GPa/~793–801°C). M1 and M2 define together a clockwise P–T path. It reveals important information related to the Neoarchean collisional orogeny, and its later overprinted by an independent orogeny with subsequent exhumation and cooling. U–Pb zircon dating of two mafic granulites samples yielded protolith formation of the mafic granulites is prior to ~2.72 Ga, and the two metamorphic age peaks of ~2.72 (M1) and ~2.0 Ga (M3), which present the peak and post-peak cooling stages, respectively. The metamorphic evolution of HP mafic granulites in the Sand River area as reconstructed in this study suggests the Neoarchean collision of the Kaapvaal and Zimbabwe cratons and a discrete Paleoproterozoic orogenic overprint followed by post-orogenic exhumation and cooling. [ABSTRACT FROM AUTHOR]

Granulite facies rocks provide important keys to evaluating collisional metamorphism in orogenic belts. The mafic granulites of Baoding in the Fuping Complex of the North China Craton occur within the Trans-North China Orogen (TNCO), a major Paleoproterozoic collisional orogen. Here, we present results from detailed investigations on newly discovered garnet pyroxenite, garnet two-pyroxene granulite, and garnet-bearing-plagioclase amphibolite using petrographic, mineralogical, geochemical, and zircon U-Pb dating methods. Our results show that the Fuping Complex metamorphic evolution in this study evolved in four stages: prograde (M1), high-pressure granulite facies (M2), granulite facies (M3), and retrograde (M4) stages. The mineral assemblage of the prograde stage (M1) consists of Amp + Pl + Q within garnet cores. The mineral assemblage of high-pressure granulite facies at the peak stage (M2) consists of Gt + Cpx + Pl + Q ± Amp, forming the garnet pyroxenite. The granulite facies stage M3 is characterized by the occurrence of orthopyroxene, with a mineral assemblage of Gt + Cpx + Opx + Amp+ Pl + Q. The early retrograde stage M4-1 includes clinopyroxenes scattered inside amphiboles, following the breakdown of garnet and clinopyroxene. The mineral assemblage of this stage comprises Amp + Pl + Q + Ilm ± Cpx. Later, in the late retrograde stage M4-2, the composition of amphiboles changed to actinolite, and epidote and chlorite started to appear in the matrix. Traditional geothermobarometry yielded P-T conditions of 700~706 °C and 6.0~6.2 kbar for prograde stage M1, 854~920 °C and 13.0~13.8 kbar for high-pressure granulite facies stage M2, 912~939 °C and 8.1~9.9 kbar for M3, 661~784 °C and 3.1~4.4 kbar for M4-1, and 637~638 °C, 1.1~1.3 kbar for M4-2, along a clockwise P-T path with a nearly isothermal decompression (ITD) and slight heating. Zircon LA-ICP-MS U-Pb dating constrains the timing of the high-pressure granulite facies metamorphic event to be between 1.83 and 1.86 Ga. Geochemical features suggest that the protoliths of the high-pressure granulites may have formed in an island arc environment within a convergent margin setting. Together with results from previous studies, our data suggest that the ~1.85 Ga metamorphic age recorded in the Fuping Complex represents a regional metamorphism in the TNCO, associated with the subduction–collision and assembly of the Eastern and Western Blocks of the NCC. [ABSTRACT FROM AUTHOR]

To ascertain the Early-to-Middle Jurassic tectonic setting in the central Great Xing'an Range, this study investigated the Early and Middle Jurassic granitoids exposed in the Chaihe area in the central Great Xing'an Range based on isotopic chronology and petrogeochemistry. The results of this study show that the Early and Middle Jurassic granitoids have emplacement ages of 179–172 Ma. Moreover, the Early and Middle Jurassic granitoids are high-K calc-alkaline unfractionated I-type granitoids and high-K calc-alkaline fractionated I-type granitoids, respectively. The magma sources of the Early and Middle Jurassic granitoids both originated from the partial melting of newly accreted lower crustal basaltic rocks. Meanwhile, the Middle Jurassic magma sources were mixed with mantle-derived materials or ocean-floor sediments formed by the dehydration and metasomatism of subducted slabs. The Early and Middle Jurassic granitoids in the study area were formed in the subduction environment of the oceanic crust, in which the Mongol-Okhotsk oceanic plate was subducted southward beneath the Eerguna and Xing'an blocks. Moreover, the Siberian plate began to collide and converge with northeast China during the Middle Jurassic. [ABSTRACT FROM AUTHOR]

The Jiao-Liao-Ji Belt (JLJB) is the most representative Paleoproterozoic orogenic belt in the North China Craton (NCC). The sedimentation, metamorphism and magmatism of the Ji'an Group and associated granites provide significant insights into the tectonic evolution of the JLJB. In this study, we have synthesized published geochemistry and geochronology data on metasedimentary, metavolcanic and igneous rocks. According to the available data, the protoliths of the metasedimentary rocks are sets of shale, wacke, arkose, quartz sandstone and carbonate, while the protoliths of the metavolcanic rocks are calc-alkaline basalt, basaltic andesite, andesite, dacite and rhyolite. The rock assemblages indicate a transformation of the tectonic environment from a passive margin to an active continental margin following the onset of plate convergence and subduction. The A2-type gneissic granite (Qianzhuogou pluton) is formed in a subsequent back-arc basin extension setting at 2.20–2.14 Ga. The Ji'an Group was finally deposited in an active continental margin during the closure of a back-arc basin at 2.14–2.0 Ga. Then, the sediments were involved in a continent–arc–continent collision between the Longgang and Nangrim blocks at ~1.95 Ga. This process was accompanied by HP granulite-facies metamorphism at ~1.90 Ga. The subsequent exhumation and regional extension resulted in decompression melting during 1.90–1.86 Ga, producing metamorphism with an isothermal decompression clockwise P–T path. The resulting metapelites are characterized by perthite + sillimanite, and mafic granulites are characterized by orthopyroxene + clinopyroxene. The S-type porphyritic granite (Shuangcha pluton) is formed during the crustal anatexis. Meanwhile, extensive anatexis produced significant heating and triggered prograde to peak metamorphism with an anticlockwise P–T path. Cordierite-bearing symplectites around the garnet in the metapelites indicate a superposed isobaric cooling metamorphism. The ages of monazites and anatectic zircons suggest that the post-exhumation cooling occurred at 1.86–1.80 Ga. The Paleoproterozoic magmatism, sedimentation and metamorphism suggest a process of subduction back-arc basin extension and closure, collision and exhumation for the tectonic evolution of the JLJB. [ABSTRACT FROM AUTHOR]

The tectonic setting of the Jiamusi–Khanka Massif in the eastern sector of the Central Asian Orogenic Belt (CAOB) in NE China is still highly controversial. This review considers all existing data to evaluate the origin of the Jiamusi–Khanka Massif. The Precambrian basement in the Jiamusi–Khanka Massif is dominated by the Neoproterozoic orthogneisses (898–891 and 757–751 Ma), the Mashan Complex (peak metamorphism at 530–500 Ma), and syntectonically deformed early Palaeozoic granitoids (530–484 Ma) related to the metamorphism of the Mashan Complex. The Mashan Complex reveals a clockwise orogen-style P–T path with peak conditions of 850–870°C/8–9 kbar followed by isothermal decompression. It was intruded by syn- (530–500 Ma) and post-tectonic (490–476 Ma) granitic rocks. The Jiamusi–Khanka Massif cannot be directly derived from the North China, South China, or Tarim cratons. Instead, it may have originated in the Siberian Craton and formed once part of the Altai-Sayan and Baikal orogens at ~500 Ma. For the Jiamusi Massif, we developed a plate tectonic model, and relate the final granulite facies metamorphism to slab break-off after consumption of a branch of the Palaeo-Asian Ocean. [ABSTRACT FROM AUTHOR]

The inhibitory effects of vitamin D on colitis have been previously documented. Global vitamin D receptor (VDR) deletion exaggerates colitis, but the relative anticolitic contribution of epithelial and nonepithelial VDR signaling is unknown. Here, we showed that colonic epithelial VDR expression was substantially reduced in patients with Crohn's disease or ulcerative colitis. Moreover, targeted expression of human VDR (hVDR) in intestinal epithelial cells (IECs) protected mice from developing colitis. In experimental colitis models induced by 2,4,6-trinitrobenzenesulfonic acid, dextran sulfate sodium, or CD[4.sup.+]CD45R[B.sup.hi] T cell transfer, transgenic mice expressing hVDR in IECs were highly resistant to colitis, as manifested by marked reductions in clinical colitis scores, colonic histological damage, and colonic inflammation compared with WT mice. Reconstitution of Vdr-deficient IECs with the hVDR transgene completely rescued Vdr-null mice from severe colitis and death, even though the mice still maintained a hyperresponsive Vdr-deficient immune system. Mechanistically, VDR signaling attenuated PUMA induction in IECs by blocking NF-kB activation, leading to a reduction in IEC apoptosis. Together, these results demonstrate that gut epithelial VDR signaling inhibits colitis by protecting the mucosal epithelial barrier, and this anticolitic activity is independent of nonepithelial immune VDR actions., 10.1172/JCI65842. Introduction Ulcerative colitis (UC) and Crohn's disease (CD) are major chronic inflammatory bowel diseases (IBDs) in humans. Although the etiology and pathogenesis of IBD remain uncertain, it is believed [...]