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IntroductionLow temperature inhibits the growth of most microorganisms. However, some microbes can grow well in a low temperature, even a freezing temperature.MethodsIn this study, the mechanisms conferring cold resistance in the cryophylactic yeast Metschnikowia (M.) pulcherrima MS612, an isolate of the epidermis of ice grapes, were investigated based on comparative transcriptome analysis.ResultsA total of 6018 genes and 374 differentially expressed genes (> 2-fold, p < 0.05) were identified using RNA-Seq. The differentially expressed genes were mainly involved in carbohydrate and energy metabolism, transport mechanisms, antifreeze protection, lipid synthesis, and signal transduction. M. pulcherrima MS612 maintained normal growth at low temperature (5°C) by enhancing energy metabolism, sterol synthesis, metal ion homeostasis, amino acid and MDR transport, while increased synthesis of glycerol and proline transport to improve its resistance to the freezing temperature (−5°C). Furthermore, cAMP-PKA and ERAD signaling pathways contribute to resist the low temperature and the freezing temperature, respectively.ConclusionThis study provides new insights into cold resistance in cryophylactic microorganisms for maneuvering various metabolism to resist different cold environment.

Background: Guishaozichuan (GSZC) granules are a traditional Chinese medicine formulation created by Professor Li (Chinese–Japanese Friendship Hospital, Beijing, China) we studied the effect of GSZC granules in rats suffering from asthma.Methods: Specific pathogen-free Sprague–Dawley rats were divided randomly into seven groups. Ovalbumin (OVA) and Al (OH)3 gel were used to create an asthma model. On day 1, rats were injected with OVA (10 mg) and an Al(OH)3 gel suspension (100 mg). One week later, rats were sensitized again. On day 15, rats were given aerosolized OVA (1%) for 30 min/day for 10 days. Gastric administration of OVA was 1 h before nebulization. At 24 h after the last stimulation, changes in airway resistance (RI) and dynamic compliance (Cdyn) in rat lungs were measured after challenge with methacholine at increasing concentrations. The contents of immunoglobulin (Ig)E, interleukin (IL)-4, IL-5, IL-13, and IL-17 in serum were measured by enzyme-linked immunosorbent assays. The percentage of eosinophils (EOS) and the white blood cell (WBC) count in bronchoalveolar lavage fluid (BALF) were counted under an optical microscope. Pathologic alterations in lung tissue were evaluated by optical microscopy, and lung injury score calculated. Expression of mucin 5AC, oligomeric mucus/gel-forming (MUC5AC) and epidermal growth factor receptor (EGFR) in lung tissue was measured by immunohistochemistry. mRNA expression of MUC5AC and EGFR in lung tissue was measured by real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR).Results: GSZC granules reduced RI markedly and improved Cdyn, decreased serum levels of IgE, IL-4, IL-5, IL-13, IL-17, %EOS and the WBC count in BALF. GSZC granules alleviated lung-tissue damage, diminished the Inflammation Score, and reduced mRNA and protein expression of MUC5AC and EGFR in lung tissue.Conclusion: GSZC granules could improve bronchial hyperresponsiveness, bronchial inflammation, and histopathologic damage in the lungs of rats suffering from asthma. This phenomenon may be related to its regulation of cytokine levels and the MUC5AC/EGFR signaling pathway.

We present new LA-ICP-MS detrital zircon U-Pb age and trace element data of the Late Mesozoic sedimentary sequences from the western Shandong and Tanlu fault zone, with the aim to constrain the depositional ages and sedimentary sources. The samples from the western Shandong have similar U-Pb age spectra, which can be divided into three major age groups, peaking age at circa 2,475–2,540 Ma, 1820–1870 Ma and 257–285 Ma, with minor Mesoproterozoic, Neoproterozoic and Paleozoic detrital zircon grains. The sample JN recovered from the Tanlu fault zone has an overwhelming majority of the Early Cretaceous detrital zircons with the age peak at circa 125 Ma, whereas the Archean and Paleoproterozoic detrital zircons are subordinate. The weighted average age of the youngest zircons show that the Santai Formation probably had begun deposition at circa 158 Ma and terminated deposition at circa 150 Ma, and the Tianjialou Formation of the Dasheng Group had begun deposition at circa 122 Ma. Our study indicates that the activity of the dinosaurs might occur during the Late Jurassic rather than the Cretaceous in the Shandong province. In addition, most detrital zircons of the studied samples are characterized by the high Th/U ratios and left-inclined REE patterns, revealing a magmatic origin. Morphologically, most detrital zircon grains characterized by angular to sub-rounded shapes indicate a middle-short distance transport from the source regions, whereas minor detrital zircon grains show rounded shapes, indicating a long-distance transport or multiphase recycling. According to detrital age populations in this study, combined with previously published data, we conclude that depositional provenances of the Santai Formation were mainly derived from the western Shandong and Jiao-Liao Belt, and minor detritus were derived from the northern part of the North China Craton and Xing-Meng orogenic belt. The sediments deposited in the Tanlu fault zone were mainly derived from the volcanic and subvolcanic rocks of the Qingshan period in the eastern Shandong, and subordinate depositional sources were from the Jiao-Liao and the basement uplift of the western Shandong, with minor supplier being derived from the Yinshan-Yanshan orogenic belt. The detrital provenance of the Santai Formation indicates that extension of the eastern NCC occurred during the Late Jurassic. The Neoproterozoic detrital zircons play a minor role in the studied strata, indicating that the large sinistral movement of the Tanlu fault zone might have occurred at the Early-Middle Jurassic and formed a paleogeographic separation of the western Shandong and eastern Shandong (Sulu orogenic belt).

The Gangdese magmatic belt of southern Tibet is an ideal place to study Neo-Tethyan subduction, continental crustal growth and reworking. However, there are still controversies with regard to the evolution of the Neo-Tethys Ocean, the magma source and the detailed diagenetic processes of igneous rocks in the Gangdese belt. The Early Cretaceous magmatic exposures are sporadic in the Gangdese magmatic belt. Thus the finding of the new exposure is key to understanding the scenarios of the Neo-Tethys Ocean and geological background of southern Tibet during the Early Cretaceous. In this contribution, we undertook systematic geochronology, whole-rock geochemistry and zircon Lu-Hf isotopic studies on a newly identified granitic pluton in the middle Gangdese belt (Quesang area), southern Tibet. The results show that zircon U-Pb dating of three representative samples yielded a weighted age of 120 ± 1.4 Ma, 117.3 ± 2.5 Ma and 114.0 ± 1.3 Ma, respectively, which indicate the emplacement and crystallization age belonging to the Aptian stage of the Early Cretaceous in response to the northward subduction of the Neo-Tethyan oceanic lithosphere beneath the Lhasa terrane. In situ zircon Lu-Hf isotopic analyses indicate that ƐHf(t) values of the studied granitic pluton are predominantly positive ranging from 7.2 to 11.4, and one zircon shows negative ƐHf(t) value (−6.26), implying that a small amount of ancient continental crustal materials might have participated in the magma evolution. Geochemically, the granite samples are enriched in large ion lithophile elements (LILE) and light rare earth elements (LREE), but depleted in heavy rare earth elements (HREE), indicating arc-type geochemical characteristics or subduction-related tectonic setting. In addition, combined with mineral assemblages, zircon Lu-Hf isotopic features and low molar Al2O3/(CaO+Na2O+K2O) (A/CNK) ratios of 0.91–1.10, the studied samples show a close affinity with I-type granites. Moreover, zircon oxygen fugacity results show that Ce4+/Ce3+ values range from 185 to 12, with a mean value of 78, indicating a low oxygen fugacity setting similar to the Chile ore-barren granitic plutons. In combination with published data, we argue that the Gangdese magmatic belt may have developed continuous magmatism (145–105 Ma), and the notion of magmatic lull might deserve more consideration during the Early Cretaceous. In this study, the Early Cretaceous granitic pluton might be the result of the northward subduction of Neo-Tethys oceanic lithosphere beneath the Lhasa terrane at a normal angle.

Background and AimFew non-invasive models were established to identify patients with non-alcoholic steatohepatitis (NASH). Liver biopsy remains the gold standard in the clinic. Decreased serum ceruloplasmin (CP) is reported in patients with non-alcoholic fatty liver disease (NAFLD). We aimed to develop a non-invasive model incorporating CP for identifying NASH from NAFLD without type 2 diabetes mellitus (T2DM).MethodsA total of 138 biopsy-proven patients with NAFLD without T2DM were enrolled. The CP ratio was calculated for standardization as the CP value divided by the lower limit of normal. The clinical, anthropometric, biochemical, and histological parameters were compared between the low and high CP ratio groups divided by the median value. Multivariate logistic regression analysis was performed to develop a model for identifying NASH in patients with NAFLD.ResultsThe medians of the high (n = 69) and low (n = 69) CP ratio groups were 1.43 (1.28–1.61) and 1.03 (0.94–1.12), respectively. A comparison of the two groups showed that the severity of steatosis, hepatocellular ballooning, inflammation activity, fibrosis, and liver iron deposition decreased along with the CP ratio (p < 0.05). The median CP ratio of patients with NASH was significantly lower than those with NAFL [1.15 (1.01–1.41) vs. 1.33 (1.24–1.54), p = 0.001]. A novel model which consists of the CP ratio, BMI, and aspartate aminotransferase (AST) was developed. The AUCs of the model in discriminating NASH from NAFLD was 0.796 (0.694–0.899) and 0.849 (0.713–0.984) in the training and validation groups, and 0.836 (0.659–1.000), 0.833 (0.705–0.962), and 0.821 (0.612–1.000) in patients with normal serum alanine aminotransferase, AST, and both levels, respectively.ConclusionsDecreased CP ratio is associated with more severe histological activity, a diagnosis of NASH, and hepatic iron deposition among patients with NAFLD without T2DM. The CP ratio model could be served as a non-invasive approach to identifying patients with NASH, which might reduce the need for liver biopsy.

Gut microbiota dysbiosis plays an important role in the progression of non-alcoholic fatty liver disease (NAFLD), and no approved drugs are available for NAFLD treatment. In this study, we aimed to explore the dynamic changes of gut microbiota at the different stages of NAFLD and determine whether ursodeoxycholic acid (UDCA) could improve liver histopathological features of non-alcoholic steatohepatitis (NASH) mice induced by a high-fat high-cholesterol (HFHC) diet and its impact on gut microbiota. 6-week-old male C57BL/6 mice were fed with a HFHC or normal diet for 12, 18, and 24 weeks, respectively, to simulate the different stages of NAFLD. 16s ribosomal RNA genes from mice fecal samples at the different time points were sequenced to evaluate the dynamic changes of the gut microbiota. Then, C57BL/6 mice were fed with a HFHC diet for 24 weeks to establish the NASH model. Different doses of UDCA were administered intragastrically for additional 4 weeks. Normal diet–fed mice were taken as control. Serum samples, liver, and intestine tissues were harvested for biochemical tests and histopathological examinations. 16s ribosomal RNA genes from mice fecal samples were sequenced to assess the structural changes of gut microbiota. HFHC diet–fed mice developed simple steatosis, steatohepatitis, and fibrosis at 12, 18, and 24 weeks, respectively. The profile of gut microbiota dynamically changed with the different stages of NAFLD. NASH mice had significantly higher abundance of Fecalibaculum, Coriobacteriaceae_UCG-002, and Enterorhabdus, and lower abundance of norank_f_Muribaculaceae, Bacteroides, and Alistipes, which were partially restored by UDCA treatment. UDCA treatment significantly attenuated hepatic inflammation of NASH mice as indicated by the sum of ballooning and lobular inflammation of the NALFD activity score (3.2 ± 0.8 vs 1.8 ± 0.8, p = 0.029), and partially restored gut microbiota dysbiosis, and increased the expression of Claudin-1 and ZO-1 in the intestine, but did not activate the suppressed Farnesoid X receptor signal pathway. Conclusions: The gut microbiota dynamically changes with the different stages of NAFLD. UDCA treatment (120 mg/kg) could partially restore gut microbiota, repair gut barrier integrity, and attenuate hepatic inflammation in the NASH mouse model.