The carbonate-hosted Pb–Zn deposits in the Sichuan–Yunnan–Guizhou (SYG) triangle region are important Indosinian deposits in South China. The Tianbaoshan deposit is a typical large Pb–Zn deposit in the SYG area and occurs as pipe-like type, hosted by Sinian dolostone. It contains ∼26 Mt Zn–Pb ore (7.76–10.09 % Zn, 1.28–1.50 % Pb and 93.6 g t−1 Ag) and >0.1 Mt Cu ore (2.55 % Cu). In this study, the detailed mineral textures, mineral chemical and sulphur isotopic compositions of the various sulphides have been analysed to constrain the abnormal enrichment mechanism and mineralization relationship. Four mineralization stages have been recognized: Stage 1, minor early pyrite (Py1) with relics and infill of intergranular dolomite or quartz grains; Stage 2, Cu mineralization with coarse-grained, elliptical crystal chalcopyrite (Cp1); (3) Stage 3, Zn mineralization with dark fine-grained sphalerite (Sph1) and light coarse-grained sphalerite (Sph2); and (4) Stage 4, as represented by a quartz–calcite assemblage with galena, minor pyrite (Py2) and chalcopyrite (Cp2). The petrography of the sulphide minerals (Py1, Cp1, Sph1 and Sph2) demonstrates a mutual inclusion relationship. The nature of this relationship from core to rim and their similar sulphur isotope values (5.5–8.3 ‰) indicates a single sulphur source, suggesting that the different mineralization types are the result of different stages of a continuous hydrothermal system. Sphalerite geothermometer study suggests that sphalerite in the Tianbaoshan deposit formed in a low-temperature (<200 °C) hydrothermal system. The low concentrations of Mn and In, low In/Ge ratios and high Fe/Cd ratios in the sphalerite are consistent with those of Mississippi Valley-type (MVT) deposits, but different from those of magmatism-related deposits (e.g. epithermal, skarn and VMS deposits). The positive δ34S values for Py1 (5.1–7.9 ‰), Cp1 (5.1–7.2 ‰), Sph1 (4.7–7.4 ‰), Sph2 (3.9–8.7 ‰), Py2 (4.4–9.3 ‰) and Cp2 (5.0–6.8 ‰) indicate a sulphur source from thermochemical reduction of coeval seawater sulphate. Widely developed dissolved textures (caverns and breccias) with massive sulphide infillings and deformed host rock remnants suggest that replacement of host dolostones by ore fluids was volumetrically significant and the ore formed nearly simultaneously with the cavities. The Tianbaoshan deposit is a typical MVT deposit, which resulted from mixing of a H2S-rich fluid and a metal-rich fluid, with thermochemical sulphate reduction occurring before ore precipitation rather than during ore precipitation.

This study is performed to figure out how the presence of diabetes affects the infection, progression and prognosis of 2019 novel coronavirus disease (COVID-19), and the effective therapy that can treat the diabetes-complicated patients with COVID-19. A multicentre study was performed in four hospitals. COVID-19 patients with diabetes mellitus (DM) or hyperglycaemia were compared with those without these conditions and matched by propensity score matching for their clinical progress and outcome. Totally, 2444 confirmed COVID-19 patients were recruited, from whom 336 had DM. Compared to 1344 non-DM patients with age and sex matched, DM-COVID-19 patients had significantly higher rates of intensive care unit entrance (12.43% vs. 6.58%, P = 0.014), kidney failure (9.20% vs. 4.05%, P = 0.027) and mortality (25.00% vs. 18.15%, P < 0.001). Age and sex-stratified comparison revealed increased susceptibility to COVID-19 only from females with DM. For either non-DM or DM group, hyperglycaemia was associated with adverse outcomes, featured by higher rates of severe pneumonia and mortality, in comparison with non-hyperglycaemia. This was accompanied by significantly altered laboratory indicators including lymphocyte and neutrophil percentage, C-reactive protein and urea nitrogen level, all with correlation coefficients >0.35. Both diabetes and hyperglycaemia were independently associated with adverse prognosis of COVID-19, with hazard ratios of 10.41 and 3.58, respectively.

Metabolically healthy obesity (MHO) might be an alternative valuable target in obesity treatment. We aimed to assess whether alternative Mediterranean (aMED) diet and Dietary Approaches to Stop Hypertension (DASH) diet were favourably associated with obesity and MHO phenotype in a Chinese multi-ethnic population. We conducted this cross-sectional analysis using the baseline data of the China Multi-Ethnic Cohort study that enrolled 99 556 participants from seven diverse ethnic groups. Participants with self-reported cardiometabolic diseases were excluded to eliminate possible reverse causality. Marginal structural logistic models were used to estimate the associations, with confounders determined by directed acyclic graph (DAG). Among 65 699 included participants, 11·2 % were with obesity. MHO phenotype was present in 5·7 % of total population and 52·7 % of population with obesity. Compared with the lowest quintile, the highest quintile of DASH diet score had 23 % decreased odds of obesity (OR = 0·77, 95 % CI 0·71, 0·83, Ptrend < 0·001) and 27 % increased odds of MHO (OR = 1·27, 95 % CI 1·10, 1·48, Ptrend = 0·001) in population with obesity. However, aMED diet showed no obvious favourable associations. Further adjusting for BMI did not change the associations between diet scores and MHO. Results were robust to various sensitivity analyses. In conclusion, DASH diet rather than aMED diet is associated with reduced risk of obesity and presents BMI-independent metabolic benefits in this large population-based study. Recommendation for adhering to DASH diet may benefit the prevention of obesity and related metabolic disorders in Chinese population.

The mechanisms of leading-edge vortex (LEV) formation and its stable attachment to revolving wings depend highly on Reynolds number ($\textit {Re}$). In this study, using numerical methods, we examined the $\textit {Re}$ dependence of LEV formation dynamics and stability on revolving wings with $\textit {Re}$ ranging from 10 to 5000. Our results show that the duration of the LEV formation period and its steady-state intensity both reduce significantly as $\textit {Re}$ decreases from 1000 to 10. Moreover, the primary mechanisms contributing to LEV stability can vary at different $\textit {Re}$ levels. At $\textit {Re} <200$, the LEV stability is mainly driven by viscous diffusion. At $200<\textit {Re} <1000$, the LEV is maintained by two distinct vortex-tilting-based mechanisms, i.e. the planetary vorticity tilting and the radial–tangential vorticity balance. At $\textit {Re}>1000$, the radial–tangential vorticity balance becomes the primary contributor to LEV stability, in addition to secondary contributions from tip-ward vorticity convection, vortex compression and planetary vorticity tilting. It is further shown that the regions of tip-ward vorticity convection and tip-ward pressure gradient almost overlap at high $\textit {Re}$. In addition, the contribution of planetary vorticity tilting in LEV stability is $\textit {Re}$-independent. This work provides novel insights into the various mechanisms, in particular those of vortex tilting, in driving the LEV formation and stability on low-$\textit {Re}$ revolving wings.

This study aimed to evaluate the performance of Cobas human papillomavirus (HPV) test in cervical cancer screening. A total of 3442 women aged ⩾20 years used Cobas HPV and hybrid capture 2 (HC2) tests were included in this study. Women with any positive result were examined by liquid-based cytology (LBC) test. Then subjects with abnormal LBC or positive Cobas HPV16/18 were further checked by colposcopy to observe the visible lesions to perform the pathological examination. Of these 3442 women, 328 cases were Cobas HPV positive, and the positive rate was 9.53% (95% confidence interval (CI) 8.50–10.53). The positive rate of HPV16, HPV18, and other 12 types of high-risk HPV were 1.54% (95% CI 1.12–1.95), 0.55% (95% CI 0.30–0.80), and 7.44% (95% CI 6.56–8.32), respectively. The coincidence rate of Cobas HPV test and HC2 test was 90% (95% CI 89.00–91.00; Kappa = 0.526) in the primary screening. Age had a non-linear relationship with Cobas HPV positive rate (χ2 = 4.240, P = 0.040) and HPV16/18 typing positive rate (χ2 = 6.610, P = 0.010). Compared with the LBC test, the Cobas HPV test had higher sensitivity when detecting patients with high cervical intraepithelial neoplasia (CIN2+ and CIN3+).

DNA methylation is one of the most important epigenetic modifications in breast cancer (BC) development, and long-term dietary habits can alter DNA methylation. Cadherin-4 (CDH4, a member of the cadherin family) encodes Ca2+-dependent cell–cell adhesion glycoproteins. We conducted a case–control study (380 newly diagnosed BC and 439 cancer-free controls) to explore the relationship of CDH4 methylation in peripheral blood leukocyte DNA (PBL DNA), as well as its combined and interactive effects with dietary factors on BC risk. A case-only study (335 newly diagnosed BC) was conducted to analyse the association between CDH4 methylation in breast tissue DNA and dietary factors. CDH4 methylation was detected using quantitative methylation-specific PCR. Unconditional logistic regressions were used to analyse the association of CDH4 methylation in PBL DNA and BC risk. Cross-over analysis and unconditional logistic regression were used to calculate the combined and interactive effects between CDH4 methylation in PBL DNA and dietary factors in BC. CDH4 hypermethylation was significantly associated with increased BC risk in PBL DNA (ORadjusted (ORadj) = 2·70, (95 % CI 1·90, 3·83), P < 0·001). CDH4 hypermethylation also showed significant combined effects with the consumption of vegetables (ORadj = 4·33, (95 % CI 2·63, 7·10)), allium vegetables (ORadj = 7·00, (95 % CI 4·17, 11·77)), fish (ORadj = 7·92, (95 % CI 3·79, 16·53)), milk (ORadj = 6·30, (95 % CI 3·41, 11·66)), overnight food (ORadj = 4·63, (95 % CI 2·69, 7·99)), pork (ORadj = 5·59, (95 % CI 2·94, 10·62)) and physical activity (ORadj = 4·72, (95 % CI 2·87, 7·76)). Moreover, consuming milk was significantly related with decreased risk of CDH4 methylation (OR = 0·61, (95 % CI 0·38, 0·99)) in breast tissue. Our findings may provide direct guidance on the dietary intake for specific methylated carriers to decrease their risk for developing BC.

The prevalence of workplace deviance has become an urgent issue for managers. Although increasing research has investigated the detriments of workplace deviance on other employees and organizations, limited research has studied the harm of workplace deviance on perpetrators themselves. This research drew from appraisal theories of emotion and sought to understand perpetrators' affective and behavioral consequences of engaging in deviance. Using a diary method, a survey consisting of 92 employees with 918 observations was conducted. The results reveal that employees' deviance is positively related to their feeling of fear and that fear overrides feelings of guilt, ultimately decreasing work engagement and organizational citizenship behavior (OCB). Importantly, perceived benevolent leadership weakens the effects of deviance on perpetrators themselves by relieving fear associated with past deviance and mitigating the negative influences of fear on OCB.

The current epidemic of type 2 diabetes mellitus (T2DM) significantly affects human health worldwide. Activation of brown adipocytes and browning of white adipocytes are considered as a promising molecular target for T2DM treatment. Mulberry leaf, a traditional Chinese medicine, has been demonstrated to have multi-biological activities, including anti-diabetic and anti-inflammatory effects. Our experimental results showed that mulberry leaf significantly alleviated the disorder of glucose and lipid metabolism in T2DM rats. In addition, mulberry leaf induced browning of inguinal white adipose tissue (IWAT) by enhancing the expressions of brown-mark genes as well as beige-specific genes, including uncoupling protein-1 (UCP1), peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), peroxisome proliferator-activated receptor alpha (PPARα), PRD1-BF-1-RIZ1 homologous domain containing protein 16 (PRDM16), cell death inducing DFFA-like effector A (Cidea), CD137 and transmembrane protein 26 (TMEM26). Mulberry leaf also activated brown adipose tissue (BAT) by increasing the expressions of brown-mark genes including UCP1, PGC-1α, PPARα, PRDM16 and Cidea. Moreover, mulberry leaf enhanced the expression of nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM) genes that are responsible for mitochondrial biogenesis in IWAT and BAT. Importantly, mulberry leaf also increased the expression of UCP1 and carnitine palmitoyl transferase 1 (CPT-1) proteins in both IWAT and BAT via a mechanism involving AMP-activated protein kinase (AMPK) and PGC-1α pathway. In conclusion, our findings identify the role of mulberry leaf in inducing adipose browning, indicating that mulberry leaf may be used as a candidate browning agent for the treatment of T2DM.

High-resolution direct numerical simulations are performed to study the turbulent shear flow of liquid metal in a cylindrical container. The flow is driven by an azimuthal Lorentz force induced by the interaction between the radial electric currents injected through electrodes placed at the bottom wall and a magnetic field imposed in the axial direction. All physical parameters, are aligned with the experiment by Messadek & Moreau (J. Fluid Mech. vol. 456, 2002, pp. 137–159). The simulations recover the variations of angular momentum, velocity profiles, boundary layer thickness and turbulent spectra found experimentally to a very good precision. They further reveal a transition to small scale turbulence in the wall side layer when the Reynolds number based on Hartmann layer thickness $R$ exceeds 121, and a separation of this layer for $R \geq 145.2$. Ekman recirculations significantly influence these quantities and determine global dissipation. This phenomenology well captured by the 2-D PSM model (Pothérat, Sommeria & Moreau, J. Fluid Mech. vol. 424, 2000, pp. 75–100) until small-scale turbulence appears and incurs significant extra dissipation only captured by 3-D simulations. Secondly, we recover the theoretical law for the cutoff scale separating large quasi-two-dimensional (Q2-D) scales from small three-dimensional ones (Sommeria & Moreau, J. Fluid Mech. vol. 118, 1982, pp. 507–518), and thus establish its validity in sheared magnetohydrodynamics (MHD) turbulence. We further find that three-componentality and three-dimensionality appear concurrently and that both the frequency corresponding to the Q2-D cutoff scale and the mean energy associated with he axial component of velocity scale with the true interaction parameter $N_t$, respectively, as $0.063 N_t^{0.37}$ and $0.126N_t^{-0.92}$.

ABSTRACT IMPACT: By assessing function of mutant (patient-specific) tp53 in zebrafish embryonal rhabdomyosarcoma will inform clinicians of the severity of mutant tp53 alleles. OBJECTIVES/GOALS: This study aims to define loss- and gain-of-function TP53 mutations by comparing effects in tp53-null and wild-type tumors. In addition, it aims to generate a rapid in vivo analysis platform to assign function to patient specific TP53 mutations in the clinic METHODS/STUDY POPULATION: To define tp53 function in ERMS pathogenesis, we previously generated a new tp53-null mutant (tp53-/-) in zebrafish by deleting the entire tp53 genomic locus using TALEN mutagenesis. tp53-/- zebrafish spontaneously develop a spectrum of tumors including sarcomas, leukemia and germ cell tumors (Ignatius…Baxi et. al., eLife) reminiscent of tumors observed in Trp53-null mice. Using the tp53-/- mutants to generate kRASG12D-induced ERMS, we discovered that tp53 is a potent repressor of metastases but rather surprisingly had no effect on self-renewal (Ignatius…Baxi et. al., eLife). Here, using tp53-/- zebrafish, we assessed effects of wild-type and mutant (patient specific) tp53 on tumor initiation, proliferation and apoptosis. RESULTS/ANTICIPATED RESULTS: ERMS tumor initiation in the tp53-/- background is observed in > 97% of animals whereas only <40% of wild-type animals develop ERMS. Additionally, tp53 is a potent suppressor of ERMS proliferation and its effect on apoptosis is minor. Next, we expressed either WT zebrafish or human TP53 in tp53-/- animals along with kRASG12D and both genes suppressed tumor initiation and growth. We co-expressed TP53C176F (found in two ERMS patients) and TP53P153del (identified in a patient with osteosarcoma in our clinic) in zebrafish ERMS, and find that the TP53C176F allele significantly suppressed tumor initiation with effects predominantly on enhanced apoptosis. However, the TP53P153del allele initiated tumors at similar frequency compared to tp53-/- animals but increased the initiation of tumors in the head musculature. DISCUSSION/SIGNIFICANCE OF FINDINGS: Different TP53 alleles identified in patient tumors have very different effects on tumorigenesis in vivo and can respond differently to potentially therapeutic compounds. Thus, the type of precision modeling demonstrated here promises to help further define patient-specific TP53 biology and improve clinical strategies in the future.

The global dairy sector is facing the challenge of reducing greenhouse gas (GHG) emissions whilst increasing productivity to feed a growing population. Despite the importance of this challenge, many developing countries do not have the required resources, specifically funding, expertise and facilities, for quantifying GHG emissions from dairy production and research. This paper aims to address this challenge by discussing the magnitude of the issue, potential mitigation approaches and benefits in quantifying GHG emissions in a developing country context. Further, the paper explores the opportunities for developing country dairy scientists to leverage resources from developed countries, such as using existing relevant GHG emission estimation models. It is clear that further research is required to support developing countries to quantify and understand GHG emissions from dairy production, as it brings significant benefits including helping to identify and implement appropriate mitigation strategies for local production systems, trading carbon credits and achieving the nationally determined contribution obligations of the Paris Agreement.

Cost-effective sampling design is a problem of major concern in some experiments especially when the measurement of the characteristic of interest is costly or painful or time-consuming. In this article, we investigate ratio-type estimators of the population mean of the study variable, involving either the first or the third quartile of the auxiliary variable, using ranked set sampling (RSS) and extreme ranked set sampling (ERSS) schemes. The properties of the estimators are obtained. The estimators in RSS and ERSS are compared to their counterparts in simple random sampling (SRS) for normal data. The numerical results show that the estimators in RSS and ERSS are significantly more efficient than their counterparts in SRS.

The aim of this study was to explore the effects and mechanisms of different starvation treatments on the compensatory growth of Acipenser dabryanus. A total of 120 fish (60·532 (sem 0·284) g) were randomly assigned to four groups (fasting 0, 3, 7 or 14 d and then refed for 14 d). During fasting, middle body weight decreased significantly with prolonged starvation. The whole-body and muscle composition, serum biochemical indexes, visceral indexes and digestive enzyme activities had been effected with varying degrees of changes. The growth hormone (GH) level in serum was significantly increased in 14D; however, insulin-like growth factor-1 (IGF-1) showed the opposite trend. The neuropeptide Y (npy) mRNA level in brain was significantly improved in 7D; peptide YY (pyy) mRNA level in intestine was significantly decreased during fasting. After refeeding, the final body weight, percentage weight gain, specific growth rate, feed intake, feed efficiency and protein efficiency ratio showed no difference between 0D and 3D. The changes of whole-body and muscle composition, serum biochemical indexes, visceral indexes and digestive enzyme activities had taken place in varying degrees. GH levels in 3D and 7D were significantly higher than those in the 0D; the IGF-1 content decreased significantly during refeeding. There was no significant difference in npy and pyy mRNA levels. These results indicated that short-term fasting followed by refeeding resulted in full compensation and the physiological and biochemical effects on A. dabryanus were the lowest after 3 d of starvation and 14 d of refeeding. Additionally, compensation in A. dabryanus may be mediated by appetite genes and GH, and the degree of compensation is also affected by the duration of starvation.

Studies have suggested an association between metabolic and cerebrocardiovascular diseases and major depressive disorder (MDD). However, the risk of metabolic and cerebrocardiovascular diseases in the unaffected siblings of patients with MDD remains uncertain. Using the Taiwan National Health Insurance Research Database, 22,438 unaffected siblings of patients with MDD and 89,752 age-/sex-matched controls were selected and followed up from 1996 to the end of 2011. Individuals who developed metabolic and cerebrocardiovascular diseases during the follow-up period were identified. Compared with the controls, the unaffected siblings of patients with MDD had a higher prevalence of metabolic diseases, such as hypertension (5.0% vs. 4.5%, p = 0.007), dyslipidemia (5.6% vs. 4.8%, p < 0.001), and obesity (1.7% vs. 1.5%, p = 0.028), and cerebrocardiovascular diseases, such as ischemic stroke (0.6% vs. 0.4%, p < 0.005) and ischemic heart disease (2.1% vs. 1.7%, p < 0.001). Logistic regression analyses revealed that the unaffected siblings of patients with MDD were more likely to develop hypertension, dyslipidemia, ischemic stroke, and ischemic heart diseases during the follow-up period than the controls. Our study revealed a familial coaggregation between MDD and metabolic and cerebrocardiovascular diseases. Additional studies are required to investigate the shared pathophysiology of MDD and metabolic and cerebrocardiovascular diseases.

This study aimed to evaluate associations between toxoplasmosis and psychiatric disorders in Taiwan based on the National Health Insurance Research Database, Taiwan (1997–2013). Patients newly diagnosed with toxoplasmosis formed the case group (n = 259), and the control group included propensity-score matched patients without toxoplasmosis (n = 1036). The primary outcome was incidence of psychiatric disorders. Cox proportional hazards regression and stratified analyses were performed to examine risk of developing specific psychiatric disorders between patients with and without toxoplasmosis. Patients with toxoplasmosis had significantly higher incidence of psychiatric disorders than those without toxoplasmosis (P = 0.016). A significant difference was found in numbers of psychiatric disorders between the two groups during 14 years of follow-up (log-rank P < 0.001). Those with toxoplasmosis had significantly higher risk of bipolar disorder [adjusted hazard ratio (aHR = 3.60, 95% confidence interval (CI) = 2.07, 7.26), depression (aHR = 4.94, 95% CI = 2.15, 11.80) and anxiety (aHR = 5.36, 95% CI = 2.98, 25.88), but no significant between-group differences were found for schizophrenia and other psychiatric disorders. In conclusion, the present nationwide population-based analysis revealed that Toxoplasma gondii infection in Taiwan significantly increases the risk for developing bipolar disorder, depression and anxiety, but not for schizophrenia and other psychiatric disorders.

A higher dietary intake or serum concentration of betaine has been associated with greater lean body mass in middle-aged and older adults. However, it remains unknown whether betaine intake is associated with age-related loss of skeletal muscle mass (SMM). We assessed the association between dietary betaine intake and relative changes in SMM after 3 years in middle-aged adults. A total of 1242 participants aged 41–60 years from the Guangzhou Nutrition and Health Study 2011–2013 and 2014–2017 with body composition measurements by dual-energy X-ray absorptiometry were included. A face-to-face questionnaire was used to collect general baseline information. After adjustment for potential confounders, multiple linear regression found that energy-adjusted dietary betaine intake was significantly and positively associated with relative changes (i.e. percentage loss or increase) in SMM of legs, limbs and appendicular skeletal mass index (ASMI) over 3 years of follow-up (β 0·322 (se 0·157), 0·309 (se 0·142) and 0·303 (se 0·145), respectively; P < 0·05). The ANCOVA models revealed that participants in the highest betaine tertile had significantly less loss in SMM of limbs and ASMI and more increase in SMM of legs over 3 years of follow-up, compared with those in the bottom betaine tertile (all Ptrend < 0·05). In conclusion, our findings suggest that elevated higher dietary betaine intake may be associated with less loss of SMM of legs, limbs and ASMI in middle-aged adults.