Lithospheric Structure Underneath the Archean Tanzania Craton and Adjacent Regions from a Joint Inversion of Receiver Functions and Rayleigh-Wave Phase Velocity Dispersion

Lithospheric structure beneath the Archean Tanzania craton and adjacent regions, including segments of the East African rift system (EARS) and the Proterozoic-early Paleozoic orogenic belts between the EARS and the craton, is imaged by a joint inversion of receiver functions and Rayleigh wave dispersion measurements derived from ambient seismic noise for shorter periods and teleseismic data for longer periods. Our resulting crustal thickness, crustal VP= VS measurements and 3D shear-wave velocity model for the upper 120 km show a clear spatial correspondence with major surficial geological features. The new results suggest the presence of a mafic layer in the bottom of the crust of the entire Archean craton, which is previously only identified beneath the southern portion of the craton. High crustal VP= VS values measured in the Rungwe Volcanic Province and most areas of the Kenya and Tanganyika rift segments can be attributed to a combined result of basaltic sediments atop the crust, magmatic intrusion, and crustal partial melting. The Kivu Volcanic Province and parts of the Kenya rift segment are characterized by localized lower-than-normal crustal VP= VS values and shear velocities in the lower crust and uppermost mantle, which, given the presence of large volume of CO2 from surficial observations, can be best interpreted by CO2-filled fractures or conduits. Lower-than-normal shear velocities in the uppermost mantle are revealed beneath almost the entire study region with the lowest values found in all the three volcanic provinces. The lowvelocities are indicative of an underplated layer formed by mantle-derived magmatic materials trapped below the Moho. The relatively low velocities beneath the volcanic provinces might be caused by a higher degree of partial melting in the uppermost mantle

All-cause mortality in metabolically healthy individuals was not predicted by overweight and obesity

BACKGROUND Metabolically healthy obesity (MHO) and metabolically healthy overweight (MH-OW) have been suggested to be important and emerging phenotypes with an increased risk of cardiovascular disease (CVD). However, whether MHO and MH-OW are associated with all-cause mortality remains inconsistent. METHODS The association of MHO and MH-OW and all-cause mortality was determined in a Chinese community-based prospective cohort study (the Kailuan study), including 93,272 adults at baseline. Data were analyzed from 2006 to 2017. Participants were categorized into 6 mutually exclusive groups, according to BMI and metabolic syndrome (MetS) status. The primary outcome was all-cause death, and accidental deaths were excluded. RESULTS During a median follow-up of 11.04 years (interquartile range, 10.74-11.22 years), 8977 deaths occurred. Compared with healthy participants with normal BMI (MH-NW), MH-OW participants had the lowest risk of all-cause mortality (multivariate-adjusted HR [aHR], 0.926; 95% CI, 0.861-0.997), whereas there was no increased or decreased risk for MHO (aHR, 1.009; 95% CI, 0.886-1.148). Stratified analyses and sensitivity analyses further validated that there was a nonsignificant association between MHO and all-cause mortality. CONCLUSIONS Overweight and obesity do not predict increased risk of all-cause mortality in metabolic healthy Chinese individuals

EXPRESSION OF USP22 AND CPC IN ORAL CANCER

Oral cancer is a common cancer of the head and neck. Oral squamous cell carcinoma (OSCC) represents almost 90% of the total cases of head and neck cancer. Ubiquitin‑specific protease 22 (USP22) is a deubiquitinating hydrolase, and it is highly expressed in various types of cancer, which also typically have a poor prognosis. Aurora‑B and Survivin, which belong to the chromosomal passenger complex, are also highly expressed in a number of types of cancer. In the present study, USP22 expression and its associations with Aurora‑B and Survivin, and the clinicopathological features in OSCC were explored. USP22 is highly expressed in OSCC. Overexpression of USP22 is associated with lymph node metastasis and histological grade (P<0.01). Additionally, the expression of USP22 was positively associated with Aurora‑B (P<0.01), Survivin (P<0.01), and Ki‑67 (P<0.01). Furthermore, USP22 small interfering RNA inhibited cell growth and reduced the expression levels of Aurora‑B, Survivin and Cyclin B, together with the upregulation of cyclin‑dependent kinase inhibitor 1A (p21). These data suggest that USP22, Aurora‑B and Survivin promote the OSCC development and may represent novel targets for OSCC diagnosis and treatment in the future

Chemical composition of the volatile oil of Chenopodium ambrosioides L. from Mianyang in Sichuan Province of China and its sub-chronic toxicity in mice

Purpose: To determine the chemical constituents of the volatile oil of Chenopodium ambrosioides L. from Mianyang in Sichuan Province of China, and assess the sub-chronic toxicity of the volatile oil in mice.Methods: The volatile chemical components were analyzed by gas chromatography-mass spectrometry (GC-MS). Sixty Kunming mice were divided into six groups of ten mice each. One group served as control (no treatment), two groups were orally administered ρ-cymene at doses of 3 and 7 mg/kg, respectively, for 27 days, while three groups received the volatile oil at doses of 10, 25 and 40 mg/kg, respectively, for the same duration. Sub-chronic toxicity in the mice was evaluated by observing their general behavior, measuring serum levels of aspartate transaminase (AST) and alanine transaminase (ALT), evaluating liver, heart, kidney and thymus indices, and assessing the histological morphology of the organs.Results: The volatile oil contained 14 chemical components, of which α-terpinene and ρ-cymene accounted for 32.89 and 24.25 %, respectively. The volatile oil caused significant (p &lt; 0.05) increase in liver index, and serum AST and ALT levels, and also induced distinct morphological changes in mouse liver, heart and kidney.Conclusion: The main volatile components of the oil are α-terpinene and ρ-cymene. The volatile oil showed dose-dependent toxicity in mice, thus lending some support for the safe use of C. ambrosioides in traditional medicine. Keywords: Chenopodium ambrosioides, Volatile oil, Oral toxicity, AST and ALT, Histopathological change

HSPA12A Is Required for Adipocyte Differentiation and Diet-Induced Obesity Through a Positive Feedback Regulation With PPARγ

Obesity is one of the most serious public health problems. Peroxisome proliferator-activated receptor γ (PPARγ) plays the master role in adipocyte differentiation for obesity development. However, optimum anti-obesity drug has yet been developed, mandating more investigation to identify novel regulator in obesity pathogenesis. Heat shock protein 12A (HSPA12A) encodes a novel member of the HSP70 family. Here, we report that obese patients showed increased adipose HSPA12A expression, which was positively correlated with increase of body mass index. Intriguingly, knockout of HSPA12A (Hspa12a−/−) in mice attenuated high-fat diet (HFD)-induced weight gain, adiposity, hyperlipidemia, and hyperglycemia compared to their wild type (WT) littermates. Increased insulin sensitivity was observed in Hspa12a−/− mice compared to WT mice. The HFD-induced upregulation of PPARγ and its target adipogenic genes in white adipose tissues (WAT) of Hspa12a−/− mice were also attenuated. Loss- and gain-of-function studies revealed that the differentiation of primary adipocyte precursors, as well as the expression of PPARγ and target adipogenic genes during the differentiation, was suppressed by HSPA12A deficiency whereas promoted by HSPA12A overexpression. Importantly, PPARγ inhibition by GW9662 reversed the HSPA12A-mediated adipocyte differentiation. On the other hand, HSPA12A expression was downregulated by PPARγ inhibition but upregulated by PPARγ activation in primary adipocytes. A direct binding of PPARγ to the PPAR response element in the Hspa12a promoter region was confirmed by chromatin immunoprecipitation assay, and this binding was increased after differentiation of primary adipocytes. These findings indicate that HSPA12A is a novel regulator of adipocyte differentiation and diet-induced obesity through a positive feedback regulation with PPARγ. HSPA12A inhibition might represent a viable strategy for the management of obesity in humans

HSPA12A Attenuates Lipopolysaccharide-Induced Liver Injury Through Inhibiting Caspase-11-Mediated Hepatocyte Pyroptosis via PGC-1α-Dependent Acyloxyacyl Hydrolase Expression

Liver dysfunction is strongly associated with poor survival of sepsis patients. Cytosolic lipopolysaccharide (LPS) sensing by Caspase-4/5/11 for pyroptosis activation is a major driver of the development of sepsis. Studies in macrophages and endothelial cells have demonstrated that LPS is inactivated by acyloxyacyl hydrolase (AOAH) and leading to desensitizing Caspase-4/5/11 to LPS. However, little is known about the cytosolic LPS-induced pyroptosis in hepatocytes during sepsis. Heat shock protein 12A (HSPA12A) is a novel member of the HSP70 family. Here, we report that LPS increased HSPA12A nuclear translocation in hepatocytes, while knockout of HSPA12A (Hspa12a−/−) in mice promoted LPS-induced acute liver injury. We also noticed that the LPS-induced Caspase-11 activation and its cleavage of gasdermin D (GSDMD) to produce the membrane pore-forming GSDMDNterm (markers of pyroptosis) were greater in livers of Hspa12a−/− mice compared with its wild type controls. Loss- and gain-of-function studies showed that HSPA12A deficiency promoted, whereas HSPA12A overexpression inhibited, cytosolic LPS accumulation, Caspase-11 activation and GSDMDNterm generation in primary hepatocytes following LPS incubation. Notably, LPS-induced AOAH expression was suppressed by HSPA12A deficiency, whereas AOAH overexpression reversed the HSPA12A deficiency-induced promotion of LPS-evoked and Caspase-11-mediated pyroptosis of hepatocytes. In-depth molecular analysis showed that HSPA12A interacted directly with peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) and increased its nuclear translocation, thereby inducing AOAH expression for cytosolic LPS inactivation, which ultimately leading to inhibition of the Caspase-11 mediated pyroptosis of hepatocytes. Taken together, these findings revealed HSPA12A as a novel player against LPS-induced liver injury by inhibiting cytosolic LPS-induced hepatocyte pyroptosis via PGC-1α-mediated AOAH expression. Therefore, targeting hepatocyte HSPA12A represents a viable strategy for the management of liver injury in sepsis patients

Spin State Disproportionation in Insulating Ferromagnetic LaCoO3 Epitaxial Thin Films

The origin of insulating ferromagnetism in epitaxial LaCoO3 films under tensile strain remains elusive despite extensive research efforts have been devoted. Surprisingly, the spin state of its Co ions, the main parameter of its ferromagnetism, is still to be determined. Here, we have systematically investigated the spin state in epitaxial LaCoO3 thin films to clarify the mechanism of strain induced ferromagnetism using element-specific x-ray absorption spectroscopy and dichroism. Combining with the configuration interaction cluster calculations, we unambiguously demonstrate that Co3+ in LaCoO3 films under compressive strain (on LaAlO3 substrate) are practically a low spin state, whereas Co3+ in LaCoO3 films under tensile strain (on SrTiO3 substrate) have mixed high spin and low spin states with a ratio close to 1:3. From the identification of this spin state ratio, we infer that the dark strips observed by high-resolution scanning transmission electron microscopy indicate the position of Co3+ high spin state, i.e., an observation of a spin state disproportionation in tensile-strained LaCoO3 films. This consequently explains the nature of ferromagnetism in LaCoO3 films

The Role of PTHLH in Ovarian Follicle Selection, Its Transcriptional Regulation and Genetic Effects on Egg Laying Traits in Hens

In hens, follicle selection is an important process affecting egg laying traits. This study investigated the role of parathyroid hormone-like hormone (PTHLH) in chicken follicle selection, its transcriptional regulation and genetic effects on egg laying traits. PTHLH and its receptor PTH1R were mainly expressed in follicles of 6–8 mm in diameter, exhibits differential expression pattern in the theca and granulosa cells of pre- and hierarchal follicles. PTHLH stimulates the proliferation of follicular granulosa and theca cells, the expression of StAR and CYP11A1 mRNA and the production of progesterone (P4) in pre-hierarchal follicles. Treatment with FSH increased PTHLH mRNA expression in pre-hierarchal follicular theca cells and hierarchal follicular granulosa cells. Two critical regions regulating chicken PTHLH transcription were revealed, each of which harbored a SNP: C&gt;T (chr1: 72530014) for AP-1 and a SNP: A&gt;G (chr1: 72531676). Hens with diplotype AC/GT were younger at first laying and laid more eggs at 32 weeks. The haplotype (G-1827T-165) with double mutations had the greatest promoter activity of chicken PTHLH transcription. Collectively, PTHLH plays an important role in chicken follicle selection by stimulating cell proliferation and steroidogenesis. Polymorphisms in chicken PTHLH promoter region are associated with egg laying traits by affecting the binding of transcription factor AP-1

The Impacts of Emission Control and Regional Transport on PM2.5 Ions and Carbon Components in Nanjing during the 2014 Nanjing Youth Olympic Games

Highly time-resolved measurements of water soluble ions, organic and elemental carbon concentrations in the particle diameter size range D-p <2.5 mu m (PM2.5) were performed at a downwind urban site in Nanjing in the western part of the Yangtze River Delta (YRD) in eastern China during the 2014 Youth Olympic Games (YOG). In this study, we discuss the impacts of emission control in Nanjing and the surrounding areas during the YOG and regional/long-range transport on PM2.5 pollution in Nanjing. The average concentrations of NO3-, SO42-, NH4+ were 12.1 +/- 9.9, 16.5 +/- 9.2, 9.0 +/- 5.4 mu g m(-3) during the YOG, and increased 34.3%, 53.7%, 43.9% after the YOG, respectively. The control of construction or on-road soil dust and control of industry led to the decrease of Ca2+ concentration by 55% and SO2 concentration by 46%. However, SO42- concentrations remained at relatively high levels, suggesting a significant impact of regional pollution to secondary fine particles in Nanjing. Strong correlations between OC and EC were observed during and after the YOG. A higher percentage (41%) of secondary organic carbon in Nanjing during the YOG periods was consistent with high potential photochemistry and low contributions from coal combustion. Lagrangian dispersion modelling results proved that the city clusters along the Nanjing and Shanghai axis were the major source region for high PM2.5 pollution in upwind Nanjing. This work shows that short-term strict control measures could improve the air quality, especially that affected by the primary pollutants; however, regional collaborative control strategy across administrative borders in the YRD is needed for a substantial improvement of air quality.Peer reviewe

DPP-4 Inhibitors as Potential Candidates for Antihypertensive Therapy: Improving Vascular Inflammation and Assisting the Action of Traditional Antihypertensive Drugs

Dipeptidyl peptidase-4 (DPP-4) is an important protease that is widely expressed on the surface of human cells and plays a key role in immune-regulation, inflammation, oxidative stress, cell adhesion, and apoptosis by targeting different substrates. DPP-4 inhibitors (DPP-4i) are commonly used as hypoglycemic agents. However, in addition to their hypoglycemic effect, DPP-4i have also shown potent activities in the cardiovascular system, particularly in the regulation of blood pressure (BP). Previous studies have shown that the regulatory actions of DPP-4i in controlling BP are complex and that the mechanisms involved include the functional activities of the nerves, kidneys, hormones, blood vessels, and insulin. Recent work has also shown that inflammation is closely associated with the elevation of BP, and that the inhibition of DPP-4 can reduce BP by regulating the function of the immune system, by reducing inflammatory reactions and by improving oxidative stress. In this review, we describe the potential anti-hypertensive effects of DPP-4i and discuss potential new anti-hypertensive therapies. Our analysis indicated that DPP-4i treatment has a mild anti-hypertensive effect as a monotherapy and causes a significant reduction in BP when used in combined treatments. However, the combination of DPP-4i with high-dose angiotensin converting enzyme inhibitors (ACEI) can lead to increased BP. We suggest that DPP-4i improves vascular endothelial function in hypertensive patients by suppressing inflammatory responses and by alleviating oxidative stress. In addition, DPP-4i can also regulate BP by activating the sympathetic nervous system, interfering with the renin angiotensin aldosterone system (RAAS), regulating Na/H2O metabolism, and attenuating insulin resistance (IR)