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The surface uplift history of the Tibetan Plateau and Himalaya is among the most interesting topics in geosciences because of its effect on regional and global climate during Cenozoic time, its influence on monsoon intensity, and its reflection of the dynamics of continental plateaus. Models of plateau growth vary in time, from pre-India-Asia collision (e.g., [almost equal to]100 Ma ago) to gradual uplift after the India-Asia collision (e.g., [almost equal to]55 Ma ago) and to more recent abrupt uplift (<7 Ma ago), and vary in space, from northward stepwise growth of topography to simultaneous surface uplift across the plateau. Here, we improve that understanding by presenting geologic and geophysical data from north-central Tibet, including magnetostratigraphy, sedimentology, paleocurrent measurements, and ⁴⁰Ar/³⁹Ar and fission-track studies, to show that the central plateau was elevated by 40 Ma ago. Regions south and north of the central plateau gained elevation significantly later. During Eocene time, the northern boundary of the protoplateau was in the region of the Tanggula Shan. Elevation gain started in pre-Eocene time in the Lhasa and Qiangtang terranes and expanded throughout the Neogene toward its present southern and northern margins in the Himalaya and Qilian Shan.

The lacustrine source rocks of the upper member of the lower Ganchaigou Formation ( E 3 2 ) in the Yingxi area are considered to be important source rocks in the Qaidam Basin in northwestern China. In this study, we investigated the organic geochemical characteristics of the source rocks by selecting representative samples of the Eocene lacustrine succession spanning 200 m. The results show that the source rock quality is at a fair to good level, and the organic matter (OM) is in the immature–low-maturity stage. The OM originated from plankton/algae and bacteria, with a fluctuating input of terrigenous plants. The source rocks were deposited in a reducing saline-hypersaline environment, with water-column stratification associated with a variable chemocline related to a fluctuating salinity. The vertical variability of the OM abundance is accompanied by simultaneous changes in the source of the OM and the lake water environment parameters, which is caused by the oscillations between drier and wetter conditions in inland Asia in the Late Eocene. The drier periods had strong evaporation and low fluvial input, which facilitated the formation of widespread water anoxia and enhanced OM preservation, while the wetter periods had higher fluvial input and moderate OM preservation conditions because the higher sedimentation rate led to a strong terrestrial dilution effect, which in turn limited the accumulation of OM.

Polypeptide N -Acetylgalactosaminyltransferase (GALNTs) are critical enzymes that initiate mucin type-O glycosylation, and are closely associated with the occurrence and development of multiple cancers. However, the significance of GALNT2 in clear cell renal cell carcinoma (ccRCC) progression remains largely undetermined. Based on public multi-omics analysis, GALNT2 was strongly elevated in ccRCC versus adjoining nontumor tissues, and it displayed a relationship with poor overall survival (OS) of ccRCC patients. In addition, GALNT2 over-expression accelerated proliferation of renal cancer cell (RCC) lines. In contrast, GALNT2 knockdown using shRNAs suppressed cell proliferation, and this was rescued by LATS2 knockdown. Similarly, GALNT2 deficiency enhanced p-LATS2/LATS2 expression. LATS2 is activated by phosphorylation (p-LATS2) and, in turn, phosphorylate the downstream substrate protein YAP. Phosphorylated YAP (p-YAP) stimulated its degradation and cytoplasmic retention, as it was unable to translocate to the nucleus. This resulted in reduced cell proliferation. Subsequently, we explored the upstream miRNAs of GALNT2. Using dual luciferase reporter assay, we revealed that miR-139-5p interacted with the 3ʹ UTR of GALNT2. Low miR-139-5p expression was associated with worse ccRCC patient outcome. Based on our experiments, miR-139-5p overexpression inhibited RCC proliferation, and this phenotype was rescued by GALNT2 overexpression. Given these evidences, the miR-139-5p-GALNT2-LATS2 axis is critical for RCC proliferation, and it is an excellent candidate for a new therapeutic target in ccRCC.

Triptolide (TP) is a diterpenoid compound extracted from the traditional Chinese medicinal herb Tripterygium wilfordii. It has antitumor and anti-inflammatory effects and stimulates immunity. However, its serious side effects, especially reproductive toxicity, limit its clinical application. This study employed a testicular injury model established by intraperitoneally injecting TP (0.2 mg/kg) in C57BL/6J male mice (age = 7–8 weeks) for 14 days. The control and TP mice’s testicular tissues were subjected to transcriptome sequencing to assess potential testicular damage mechanisms. Based on the transcriptome sequencing results and relevant literature reports, further experiments were performed. In addition, to alleviate triptolide-induced testicular damage, we treated the mice with N-acetyl-L-cysteine (NAC). The acquired data revealed that compared with the control mice, the TP-treated mice’s testes indicated severe damage. Transcriptome sequencing identified differentially expressed genes that showed enrichment in cell differentiation, apoptotic process, cell cycle, glutathione (GSH) metabolism, and the p53 signaling pathway. Furthermore, TUNEL assays and Western blot analysis showed that in the TP mice’s testicular tissues, the spermatocytes had mitochondrial pathway apoptosis as well as abnormal mitochondrial morphology and structure. Triptolide induces oxidative stress in testicular tissue by enhancing pro-oxidative systems and inhibiting antioxidant systems. NAC reduced testicular damage and apoptosis by alleviating TP-induced oxidative stress. This study also employed a GC2 cell line for in-vitro analyses, and the results were consistent with the in vivo experiments. This study provides evidence for alleviating TP’s adverse effects on the male reproductive system for better clinical application.

The organic-rich black shale in the Qiangtang Basin, northern Tibet, has long been the focus of petroleum geologists. This paper discusses the characteristics and maturity parameters of such biomarkers of the shale as n-alkanes, acyclic isoprenoids, terpenoids and steranes, using gas chromatographic (GS) and mass spectrometric (MS) techniques. n-Alkanes are characterized by a typical unimodal distribution, with dominant low carbon numbers of [nC.sub.16]-[nC.sub.19], which suggests that the organic matter sources are mainly algae and planktonic organisms along with terrestrial higher plants. Furthermore, acyclic isoprenoid alkanes pristane (Pr) and phytane (Ph) are the most abundant, the Pr/Ph ratio being 0.06-0.70. The phytane dominance indicates that organic matter deposited in a reducing environment. In addition, the [C.sub.31]22S/(22S + 22R) hopanes ratio is 0.58-0.59, that of [C.sub.29]20S/(20S + 20R) regular steranes 0.43-0.59, and [alpha][beta][beta]/([alpha][beta][beta] + [alpha][alpha][alpha]) 0.39-0.65. These maturity parameters show that organic matter is in the maturity stage, while it is slightly more mature in the Biluocuo (BLC) section of the Qiangtang Basin than in the Ganbeixiama (GB) section. As indicated by the biomarkers values, the Jurassic source rocks in the two researched sections have a certain hydrocarbon potential.

As a special sedimentary grain type, the coated grain （with an ooid model） has been known for two centuries due to its fasci- nating special fabric and genesis developments. The leading factors in forming the coated grain consist mainly of： （1） micro- organism movement field; （2） chemical sedimentary effect; （3） hydrodynamic force environment and topography condition; （4） abundant core material supply; （5） embedding condition; and （6） humic acids condition in water medium. With the devel- opment of the coated grain genesis, the single factor theory cannot reasonably explain the exact formation of the surface sedi- ment of coated grain. Here, we find a new way to study the coated grain on the basis of traditional research methods. The Wenquan area on the northeast edge of the Qiangtang Basin is one of the few areas where the coated grain is developing, and is a rare ＂natural laboratory＂ for the study of the coated grain and the thermal spring sediment. The oolitic sinter of the area has the triaxiality modality of pea polymer, and is obviously different from the karst travertine and the normal lacustrine ooid. We found that the hot spring water in the Wenquan area has higher partial pressure of CO2 （Pco2） and saturation index of the cal- cite （Sic） than normal. Macrocosmically, the oolitic sinter is shaped like a pea, and its grains and gap fillings are light yellow. Microcosmically, the sinter grain forms six types of fundamental lamina, and those six types are developed to be four grain types with different combinations. The C-axis of the mineral grain of sinter cement （calcite） is normal to the lamina face, and grows on it with distinct generation formations. In short, the grain type of oolitic sinter is the oncoid, with the grain develop- ment caused by the factors such as the shallow water of strong hydrodynamic force, the special hydrochemistry condition, and the extensive algae activities （diatom）.

The Devonian–Carboniferous boundary is one of the most important turning points in geological history, marked by the Late Paleozoic Ice Age and Late Devonian extinction. This study investigates the carbon isotope stratigraphy across the Devonian–Carboniferous boundary in Lhasa block, Tibet, China, which was part of the Gondwana continent during that time. The carbon isotope curves show a significant negative excursion trend, consistent with those of the South China block and other regions on the Laurentia continent. This global negative shift may be attributed to the burial of significant amounts of 12C-rich organic matter in strata, a consequence of the Late Devonian extinction event. Based on the carbon isotope curve and stratigraphic data of the Lhasa block, this study determined, for the first time, the specific horizon of the Devonian–Carboniferous boundary in Tibet, which is located between grayish white bioclastic limestone and yellowish-brown sandy limestone in the upper part of the Chaguoluoma Formation (D1C1ĉ). These findings provide a new reference for the international stratigraphic community to reconsider the position of GSSP on the Devonian–Carboniferous boundary, as well as study the Late Devonian mass extinction and Late Paleozoic glaciation.

The Upper Jurassic black rock series of the Amdo area of north-central Tibet have attracted attention because of its organic-rich matter and oil seepage in the rock series. Abundant ammonites of Aulacosphinctes and Virgatosphinctes as well as bivalves including Buchia and Chlamys, are well preserved in the Qiangmuleiqu Formation of the Middle to Late Tithonian (Late Jurassic). The total rare earth elements (ΣREE) abundance of the formation varies from 18.814 to 46.818 ppm and is lower than that of an average in marine shales. Inter-element correlations suggest that the shale-normalized REE patterns provide the information about the origin of sedimentary rocks (i.e., not affected by diagenesis), and can be used as a potential indicator for eustatic sea-level changes. The [Ce.sub.anom] values gradually increased from -0.015 to -0.238from the lower to middle part of the series, indicating a rise in sea level. The [Ce.sub.anom] then dropped to -0.081, suggesting a lowering of sea level. From the middle to upper part of the section, there are two more sea-level fluctuations indicated by variations of cerium anomaly values. Thus, sea-level fluctuations occurred three times in this Late Jurassic section, with major episodes of eustatic rise took place in the lower-middle part of this section. These episodic cycles show that the sediments in the Amdo area of north-central Qiangtang basin were deposited in continental shelf or deep-water continental slope environments, which is not in agreement with the previous views that there are no deep-water sediments in Qiangtang basin. Our results call for further studies to be undertaken on Jurassic stratigraphic framework and tectono-sedimentary evolution in Qiangtang basin, northern Tibet.

The Qinghai-Tibet Plateau is located in the east section of the Tethys region, which produces great amounts of oil and gas whose reserves are one of the most abundant in the world. The plateau includes two explora­tion areas: a Mesozoic marine basin and a Cenozoic continental facies. At pre­sent, the Qiangtang Basin in the Qinghai-Tibet Plateau is believed to be the marine basin with the most extensive oil and gas exploration prospects in the world; however, the thrust-nappe structure movement in the Cretaceous-Cenozoic Period caused massive surface exposure which damaged the oil reservoirs. In this paper, the paleo-oil reservoir exposure area was used as a window to reveal the massively exposed underground distribution of oil and gas reservoirs in the Southern Qiangtang Depression, and the reservoirs were analyzed in detail. The composition of biomarkers and the charac­teris­tics of carbon isotopes of crude oil in the reservoirs were identified via comparison of oil source rocks. Our findings indicated that the oil shale series source rock from the Biluocuo region of the Qiangtang Basin repre­sents the main source rocks of the paleo-oil reservoirs.

Copper ionophore NSC319726 has attracted researchers' attention in treating diseases, particularly cancers. However, its potential effects on male reproduction during medication are unclear. This study aimed to determine whether NSC319726 exposure affected the male reproductive system. The reproductive toxicity of NSC319726 was evaluated in male mice following a continuous exposure period of 5 weeks. The result showed that NSC319726 exposure caused testis index reduction, spermatogenesis dysfunction, and architectural damage in the testis and epididymis. The exposure interfered with spermatogonia proliferation, meiosis initiation, sperm count, and sperm morphology. The exposure also disturbed androgen synthesis and blood testis barrier integrity. NSC319726 treatment could elevate the copper ions in the testis to induce cuproptosis in the testis. Copper chelator rescued the elevated copper ions in the testis and partly restored the spermatogenesis dysfunction caused by NSC319726. NSC319726 treatment also decreased the level of retinol dehydrogenase 10 (RDH10), thereby inhibiting the conversion of retinol to retinoic acid, causing the inability to initiate meiosis. Retinoic acid treatment could rescue the meiotic initiation and spermatogenesis while not affecting the intracellular copper ion levels. The study provided an insight into the bio-safety of NSC319726. Retinoic acid could be a potential therapy for spermatogenesis impairment in patients undergoing treatment with NSC319726.