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The Luxi district presents an exceptional research area for the investigation of the significant role played by magma exsolution fluids in the mineralization process of Au–Cu deposits. A particularly noteworthy occurrence within this region is the Yi'nan Tongjing Au–Cu skarn deposit, situated in the central-southern part of the Luxi district. This deposit primarily occurs in the contact zone between the early Cretaceous Tongjing complex and the Proterozoic to Cambrian sequences. The ore formation process observed in this deposit can be categorized into three distinct stages: (I) thermal metamorphism, (II) prograde alteration, and (III) retrograde alteration. The retrograde alteration stage is further divided into four sub-stages: late skarn (III-1), oxide (III-2), sulfide (III-3), and late quartz-calcite (III-4). It is primarily during the III-3 sub-stage that gold mineralization occurs. Petrographic analysis has identified three types of fluid inclusions (FIs) within garnet, quartz, and calcite grains. These include liquid-rich two-phase aqueous FIs, vapor-rich two-phase aqueous FIs, and halite-bearing multi-phase FIs. The homogenization temperatures of fluid inclusions from stages II, III-3, and III-4 range between 430–457 °C, 341–406 °C, and 166–215 °C (first to third quartiles), respectively. The garnet samples from stage II exhibit hydrogen and oxygen isotope compositions (δ18OH2O = 6.8‰ and δD = −73‰) that are indicative of a typical magma source. However, the hydrogen and oxygen isotopes of sub-stages III-1, III-2, and III-3 (δ18OH2O = 7.32‰ to 9.74‰; δD = −107‰ to −81.9‰) fall below the magma water box while the hydrogen and oxygen isotope values of III-4 (δ18OH2O = −5.3‰ to −0.9‰ and δD = −103.8‰ to −67‰) tend to move towards the meteoric water line. Furthermore, the ore-forming fluid displays characteristics of a mixture between the crustal and mantle fluids. The Tongjing complex occurred along a weakened fault zone, initiating a process of thermal metamorphism upon contact with the wall rock. This thermal metamorphism resulted in the formation of diverse assemblages, including hornfels, reaction skarns, and skarnoids. Subsequently, the upward movement of ore-forming fluids triggered exsolution which led to the establishment of a high-temperature, medium-salinity NaCl–H2O system with a single phase at depths ranging from 1–3 km. This marked the formation of the prograde alteration stage. Afterward, the ore-forming fluid underwent water–rock interactions and the admixture of meteoric water at a depth of 1–2 km. These processes facilitated phase separation, commonly referred to as boiling, resulting in the transformation of the ore-forming fluid into higher salinity fluids and lower-density gases. This evolutionary transition ultimately induced the precipitation and liberation of gold and copper from the fluid. [ABSTRACT FROM AUTHOR]

The landscape of current cancer immunotherapy is dominated by antibodies targeting PD-1/PD-L1 and CTLA-4 that have transformed cancer therapy, yet their efficacy is limited by primary and acquired resistance. The blockade of additional immune checkpoints, especially TIGIT and LAG-3, has been extensively explored, but so far only a LAG-3 antibody has been approved for combination with nivolumab to treat unresectable or metastatic melanoma. Here we report the development of a PDL1 × TIGIT bi-specific antibody (bsAb) GB265, a PDL1 × LAG3 bsAb GB266, and a PDL1 × TIGIT × LAG3 tri-specific antibody (tsAb) GB266T, all with intact Fc function. In in vitro cell-based assays, these antibodies promote greater T cell expansion and tumor cell killing than benchmark antibodies and antibody combinations in an Fc-dependent manner, likely by facilitating T cell interactions (bridging) with cancer cells and monocytes, in addition to blocking immune checkpoints. In animal models, GB265 and GB266T antibodies outperformed benchmarks in tumor suppression. This study demonstrates the potential of a new generation of multispecific checkpoint inhibitors to overcome resistance to current monospecific checkpoint antibodies or their combinations for the treatment of human cancers. [ABSTRACT FROM AUTHOR]

In architectural design course of the SWJU Rim Wisdom City Hotel, the authors explored the innovation and business model of the maker space, analyzed the junctions between future needs of innovation and business activities and hotel functions, took the SWJU Rim Wisdom City as the design background, made the hotel design scheme based on research fruits and conceptual logic, and finished the coursework from research to design. [ABSTRACT FROM AUTHOR]

Objective: To investigate the potential association of DNMT3a's single nucleotide polymorphism with susceptibility to noise-induced hearing loss( NIHL) in Chinese noise-exposed workers., Methods: A case-control study was performed, and 998 noise-exposed workers from a chemical fibre factory and an energy company, who underwent occupational health examination in 2015, were enrolled as study subjects. Then, general information and noise exposure of the study subjects were obtained through questionnaire survey and on-site noise detection. According to the result of audiological evaluation, they were divided into case group( n = 498, high-frequency threshold shift >25 dB) and man-matched control group( n = 500, high-frequency threshold shift ≤25 dB). At last, genotyping of DNMT3a rs7590760 was conducted with TaqMan-PCR technique., Results: In the dominant model, the distribution of rs7590760 genotypes between the case group and the control group was statistically significant( P = 0. 001). The NIHL risk of subjects with CC/CG genotype is 1. 56 times the risk of those carrying GG genotype, with an adjusted OR = 1. 56( 95% CI 1. 22-2. 01). After the noise exposure period and noise exposure intensity were stratified, the adjusted OR values for noise exposure period ≤16 years, > 16 years and noise intensity ≤85, 86-92 and >92 dB were respectively 1. 67( 95% CI 1. 17-2. 38), 1. 52( 95% CI 1. 06-2. 17), 1. 56( 95% CI 1. 06-2. 30), 1. 67( 95% CI 0. 94-2. 99) and 1. 51( 95% CI 1. 01-2. 26)., Conclusion: The CC/CG genotype of rs7590760 in DNMT3a gene is a potential risk factor for noise-induced hearing loss in Chinese noise-exposed workers.