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There is still controversy about optimal dietary iodine intake as the Universal Salt Iodization (USI) policy enforcement in China. A modified iodine balance study was thus conducted to explore the suitable iodine intake in Chinese adult males using the iodine overflow hypothesis. In this study, 38 apparently healthy males (19.1±0.6 years) were recruited and provided with designed diets. After the 14-days iodine depletion, daily iodine intake gradually increased in the 30-days iodine supplementation, consisting of 6 stages and each of 5-days. All foods and excreta (urine, faeces) were collected to examine daily iodine intake, iodine excretion and the changes of iodine increment in relation to those values at stage 1. The dose-response associations of iodine intake increment with excretion increment were fitted by the mixed effects models (MEMs), as well as with retention increment. Daily iodine intake and excretion were 16.3 and 54.3 μg/day at stage 1, and iodine intake increment increased from 11.2 μg/day at stage 2 to 118.0 μg/day at stage 6, whilst excretion increment elevated from 21.5 to 95.0 μg/day. A zero iodine balance was dynamically achieved as 48.0 μg/day of iodine intake. The estimated average requirement (EAR) and recommended nutrient intake (RNI) were severally 48.0 and 67.2 μg/day, which could be corresponded to a daily iodine intake of 0.74 and 1.04 μg/kg/day. The results of our study indicate that roughly half of current iodine intakes recommendation could be enough in Chinese adult males, which would be beneficial for the revision of dietary reference intakes (DRIs).
Coastal eutrophication and hypoxia remain a persistent environmental crisis despite the great efforts to reduce nutrient loading and mitigate associated environmental damages. Symptoms of this crisis have appeared to spread rapidly, reaching developing countries in Asia with emergences in Southern America and Africa. The pace of changes and the underlying drivers remain not so clear. To address the gap, we review the up-to-date status and mechanisms of eutrophication and hypoxia in global coastal oceans, upon which we examine the trajectories of changes over the 40 years or longer in six model coastal systems with varying socio-economic development statuses and different levels and histories of eutrophication. Although these coastal systems share common features of eutrophication, site-specific characteristics are also substantial, depending on the regional environmental setting and level of social-economic development along with policy implementation and management. Nevertheless, ecosystem recovery generally needs greater reduction in pressures compared to that initiated degradation and becomes less feasible to achieve past norms with a longer time anthropogenic pressures on the ecosystems. While the qualitative causality between drivers and consequences is well established, quantitative attribution of these drivers to eutrophication and hypoxia remains difficult especially when we consider the social economic drivers because the changes in coastal ecosystems are subject to multiple influences and the cause–effect relationship is often non-linear. Such relationships are further complicated by climate changes that have been accelerating over the past few decades. The knowledge gaps that limit our quantitative and mechanistic understanding of the human-coastal ocean nexus are identified, which is essential for science-based policy making. Recognizing lessons from past management practices, we advocate for a better, more efficient indexing system of coastal eutrophication and an advanced regional earth system modeling framework with optimal modules of human dimensions to facilitate the development and evaluation of effective policy and restoration actions.
The association between time to positivity (TTP) of blood culture and the clinical prognosis of patients with Klebsiella pneumoniae bloodstream infection (BSI) remains unclear. A retrospective study of 148 inpatients with BSI caused by K. pneumoniae was performed at Shanghai Tongji Hospital, China, from October 2016–2020. The total in-hospital fatality rate was 32%. The median TTP was 11.0 (7.7–16.1) h and the optimal cutoff for prediction of in-hospital mortality was 9.4 h according to the ROC curve. Early TTP (<9.4 h) was a risk factor for in-hospital mortality by univariate analysis (OR = 2.5, 95% CI 1.2–5.0, P = 0.01), but not by multivariate analysis (OR = 2.7, 95% CI 1.0–7.4, P = 0.06). Old age, serum creatinine, white blood cells, and C-reactive protein values were risk factors for in-hospital mortality by multivariate analysis. Early TTP was not a risk factor for septic shock (OR = 1.8, 95% CI 0.6–5.1, P = 0.27) or ICU admission (OR = 1.0, 95% CI 1.0–1.0, P = 0.32). In conclusion, the in-hospital fatality rate of patients with K. pneumoniae BSI was relatively high and associated with an early TTP of blood cultures. However, no increased risk of mortality, septic shock or ICU admission was evident in early TTP patients.
High-power continuous-wave single-frequency Er-doped fiber amplifiers at 1560 nm by in-band and core pumping of a 1480 nm Raman fiber laser are investigated in detail. Both co- and counter-pumping configurations are studied experimentally. Up to 59.1 W output and 90% efficiency were obtained in the fundamental mode and linear polarization in the co-pumped case, while less power and efficiency were achieved in the counter-pumped setup for additional loss. The amplifier performs indistinguishably in terms of laser linewidth and relative intensity noise in the frequency range up to 10 MHz for both configurations. However, the spectral pedestal is raised in co-pumping, caused by cross-phase modulation between the pump and signal laser, which is observed and analyzed for the first time. Nevertheless, the spectral pedestal is 34.9 dB below the peak, which has a negligible effect for most applications.
With the disease spectrum changing in China, type 2 diabetes mellitus (T2DM) has become the main chronic disease which affects people’s health severely, bring patients serious economic burden of disease. For T2DM patients, reliable quality of evidence in decision-making are significant, improving the efficiency of the adjustment of the National Reimbursement Drug List (NRDL). Based on the Consolidated Health Economic Evaluation Reporting Standards (CHEERS), we aimed to evaluate the quality of all published pharmacoeconomic evaluations on T2DM drugs in 2020 NRDL.
Because the 2020 NRDL came into effect on 1 March 2021, we searched all published pharmacoeconomic evaluations about T2DM drugs in 2020 NRDL before March 2021 in China National Knowledge Infrastructure (CNKI), Wan fang Data, China Science and Technology Journal Database (VIP), PubMed, and Web of Science. According to the criterion of inclusion and exclusion, all documents were screened and then relevant basic information of targeted documents was extracted. The quality was evaluated by calculating the final scores based on CHEERS. Two reviewers assessed each publication’s quality using the CHEERS instrument and summarized study quality.
A total of 910 papers were searched, and 24 papers were included. These involved six T2DM drugs, specifically IDegAsp, exenatide, liraglutide, lixisenatide, dapagliflozin and empagliflozin. The average score was 18.31, the standard deviation was 3.67, and the average scoring rate was 77.41 percent. Among all items, “characterizing heterogeneity” scored 0.04, least satisfied with requirements. “Setting and location”, “choice of health outcomes” and “assumptions” scored one, most satisfied with requirements. Among the average scores of all parts, “results” scored lowest at 0.55, and “methods” scored highest at 0.85. The Wilcoxon sum-rank tests showed that score rate which represented reporting quality of economic evaluation (EE) was significantly related to “journal type”, “EEs type”, “model choice” and “study perspective”.
The methodological quality of pharmacoeconomic evaluations about T2DM drugs in 2020 NRDL needs to be improved. Improving the quality of literature is the basic guarantee of scientific decision-making in national medical insurance negotiation.
Genetic mutations of fused in sarcoma (FUS) causing amyotrophic lateral sclerosis (ALS) may disrupt mRNA splicing events. For example, the FUS c.1394-2delA variant was reported in two western ALS patients, but its molecular mechanism is unclear. In this study, we aim to investigate FUS splice site mutations in Chinese ALS patients.
Sanger sequencing was used to identify FUS splicing mutations in Chinese ALS patients. We combined a deep learning tool (SpliceAI), RNA sequencing, and RT-PCR/RT-qPCR to analyze the effect of FUS c.1394-2delA mutation on RNA splicing and expression. AlphaFold was used to predict the protein structure of mutant FUS. In transfected cell lines, we used immunofluorescence to assess cytoplasmic mislocalization of mutant FUS protein.
We identified a de novo FUS splice acceptor site mutation (c.1394-2delA, p. Gly466Valfs*14) in one Chinese sporadic ALS patient, which is linked to exon 14 skipping, and upregulated total FUS mRNA expression. The FUS splice site mutation was predicted to be translated into a truncated protein product at C-terminal. In vitro studies revealed that the FUS mutation increased cytoplasmic mislocalization in both HEK293T and SH-SY5Y cells.
We identified a de novo FUS splicing mutation (c.1394-2delA, p. Gly466Valfs*14) in 1 out of 233 Chinese ALS patients. It caused abnormal RNA splicing, upregulated gene expression, truncated FUS translation, and cytosolic mislocalization. Our findings suggested that FUS splice site mutation is rare in Chinese ALS patients and extended our knowledge of molecular mechanisms of the FUS c.1394-2delA mutation.
Many protected areas worldwide have been established to protect the last natural refuges of flagship animal species. However, long-established protected areas do not always match the current distributions of target species under changing environmental conditions. Here we present a case study of the Asian elephant Elephas maximus in Xishuangbanna, south-west China, to evaluate whether the established protected areas match the species’ current distribution and to identify key habitat patches for Asian elephant conservation. Our results show that currently only 24.5% of the predicted Asian elephant distribution in Xishuangbanna is located within Xishuangbanna National Nature Reserve, which was established for elephant conservation. Based on the predicted Asian elephant distribution, we identified the most important habitat patches for elephant conservation in Xishuangbanna. The three most important patches were outside Xishuangbanna National Nature Reserve and together they contained 43.3% of the estimated food resources for Asian elephants in all patches in Xishuangbanna. Thus, we identified a spatial mismatch between immobile protected areas and mobile animals. We recommend the inclusion of the three identified key habitat patches in a new national park currently being planned by the Chinese authorities for the conservation of the Asian elephant.
In this work, a confined-doped fiber with the core/inner-cladding diameter of 40/250 μm and a relative doping ratio of 0.75 is fabricated through a modified chemical vapor deposition method combined with the chelate gas deposition technique, and subsequently applied in a tandem-pumped fiber amplifier for high-power operation and transverse mode instability (TMI) mitigation. Notably, the impacts of the seed laser power and mode purity are preliminarily investigated through comparative experiments. It is found that the TMI threshold could be significantly affected by the seed laser mode purity. The possible mechanism behind this phenomenon is proposed and revealed through comprehensive comparative experiments and theoretical analysis. Finally, a maximum output power of 7.49 kW is obtained with the beam quality factor of approximately 1.83, which is the highest output power ever reported in a forward tandem-pumped confined-doped fiber amplifier. This work could provide a good reference and practical solution to improve the TMI threshold and realize high-power high-brightness fiber lasers.
Using one-dimensional branching Brownian motion in a periodic environment, we give probabilistic proofs of the asymptotics and uniqueness of pulsating traveling waves of the Fisher–Kolmogorov–Petrovskii–Piskounov (F-KPP) equation in a periodic environment. This paper is a sequel to ‘Branching Brownian motion in a periodic environment and existence of pulsating travelling waves’ (Ren et al., 2022), in which we proved the existence of the pulsating traveling waves in the supercritical and critical cases, using the limits of the additive and derivative martingales of branching Brownian motion in a periodic environment.
High-molecular-weight glutenin subunits (HMW-GS) contribute to dough elasticity and bread baking quality in wheat. In this study, wheat varieties were classified based on their HMW-GS composition into three groups: 1Dx5 (5 + 10, Gaoyou 8901, Xinmai 28, Xinmai 19, Xinmai 26 and Jinbaoyin), 1Dx2 (2 + 12, Zhoumai 24, Xinmai 9 and Yumai) and 1Dx4 (4 + 12, Aikang 58). Sequence analysis showed that 1Dx-GY8901, 1Dx-XM28, 1Dx-XM19 and 1Dx-XM26 were similar to the 1Dx5 gene and clustered on the same branch, while 1Dx-AK58, 1Dx-ZM24, 1Dx-JBY, 1Dx-YM, 1Dx-XM9 and 1Dx-JBY were more similar to the 1Dx2 gene and clustered on the same branch with 1Dx.2.2. There was a mutation of Ser to Cys at position S2, for an extra Cys in the repeat regions of 1Dx-XM19, 1Dx-XM26, 1Dx-XM28 and 1Dx-GY8901. The wheat HMW-GS genes exhibited similar percentages of α-helix, extended strand, β-turn and random coil structure, with ranges of 13.33–13.59, 4.77–5.78, 7.08–9.18 and 72.3–73.94%, respectively. Sequence conservation and the composition of HMW-GS subunits were also analysed for a series of strong gluten wheat varieties, Xinmai 9 (1, 7 + 8, 2 + 12), Xinmai 19 (1, 7 + 9, 5 + 10), Xinmai 26 (1, 7 + 8, 5 + 10) and Xinmai 28 (1, 7 + 9, 5 + 10). The results of this work should facilitate future breeding efforts and provide the theoretical basis for wheat quality improvement.
Enstrophy production and flow topology are numerically investigated for statistically stationary compressible isotropic turbulence in vibrational non-equilibrium with a large-scale thermal forcing. The net enstrophy production term is decomposed into solenoidal, dilatational and isotropic dilatational terms based on the Helmholtz decomposition. From the full flow field perspective, the net enstrophy production mainly stems from the solenoidal term. For the dilatational and isotropic dilatational terms, although their local magnitudes can be considerable, the positive values in the compression region and the negative values in the expansion region cancel out on average. For the solenoidal component of the deviatoric strain-rate tensor, the statistical properties of its eigenvalues and alignments between vorticity and its eigenvectors are nearly independent of the local dilatation and vibrational relaxation. The solenoidal components of enstrophy production along three eigendirections are thus mainly affected by the vorticity. For the dilatational component of deviatoric strain-rate tensor, the statistical properties of its eigenvalues and alignments between vorticity and its eigenvectors closely relate to the local dilatation and vibrational relaxation. The dilatational components of enstrophy production along three eigendirections are therefore affected by the vorticity, eigenvalues and alignments between the vorticity and eigenvectors. The topological classification proposed by Chong et al. (Phys. Fluids, vol. 2, issue 5, 1990, pp. 765–777) is employed to decompose the flow field into various flow topologies. In the strong compression and strong expansion regions, the relaxation effects on the volume fractions of flow topologies and their relative contributions to the local enstrophy production are significant.
A method is presented for configuration selection to obtain the best tip-over stability of a modular reconfigurable mobile manipulator (MRMM) under various application situations. The said MRMM consists of a modular reconfigurable robot (MRR) mounted on a mobile platform. The MRR in different configurations creates different wrenches onto the mobile platform, leading to different tip-over moments of the MRMM, even though the joint speeds or tip speeds remain the same. The underlying problem pertains to selecting one configuration of MRR for reconfiguration that would obtain the best tip-over stability under a given application. First, all the permissible configurations are identified through an enumeration method. Then, the feasible configurations are determined based on application-oriented workspace classifications. At last, two workspace indices, vertical reach and horizontal reach, are used to select an optimal configuration. The tip-over stability analysis and evaluation of MRMM are carried out for verification for three cases including vertical, horizontal, and general 3D space applications. The results demonstrate the effectiveness of the proposed method.
Aberrations in how people form expectations about rewards and how they respond to receiving rewards are thought to underlie major depressive disorder (MDD). However, the underlying mechanism linking the appetitive reward system, specifically anticipation and outcome, is still not fully understood. To examine the neural correlates of monetary anticipation and outcome in currently depressed subjects with MDD, we performed two separate voxel-wise meta-analyses of functional neuroimaging studies using the monetary incentive delay task. During reward anticipation, the depressed patients exhibited an increased response in the bilateral middle cingulate cortex (MCC) extending to the anterior cingulate cortex, the medial prefrontal cortex, the left inferior frontal gyrus (IFG), and the postcentral gyrus, but a reduced response in the mesolimbic circuit, including the left striatum, insula, amygdala, right cerebellum, striatum, and IFG, compared to controls. During the outcome stage, MDD showed higher activity in the left inferior temporal gyrus, and lower activity in the mesocortical pathway, including the bilateral MCC, left caudate nucleus, precentral gyrus, thalamus, cerebellum, right striatum, insula, IFG, middle frontal gyrus, and temporal pole. Our findings suggest that cMDD may be characterised by state-dependent hyper-responsivity in cortical regions during the anticipation phase, and hypo-responsivity of the mesocortico-limbic circuit across the two phases of the reward response. Our study showed dissociable neural circuit responses to monetary stimuli during reward anticipation and outcome, which help to understand the dysfunction in different aspects of reward processing, particularly motivational v. hedonic deficits in depression.
Pharmacological treatment of major depressive disorder is often inefficient, and multiple strategies are used for inadequate response to antidepressants. Second-generation antipsychotics are used as augmentation measures in clinical practice; evidence of their efficacy and acceptability is insufficient, and it remains confusing as to which drug should be selected first. In this systematic review and network meta-analysis, we included randomised controlled trials of second-generation antipsychotics used as adjunctive treatment in patients with suboptimal responses. Outcome measures were efficacy (response and remission) and acceptability (dropout due to any reason and adverse events). Thirty-three trials comprising 10 602 participants were included. Regarding efficacy, response rates indicated that all antipsychotics except for ziprasidone were more efficacious than the placebo, with the odds ratios (ORs) ranging from 1.34 for olanzapine and cariprazine [95% credible interval (CrI) 1.04–1.73 and 1.07–1.67, respectively] to 2.17 for risperidone (95% CrI 1.38–3.42). When considering remission, cariprazine was not effective (OR 1.21, 95% CrI 0.96–1.54). For acceptability, quetiapine (OR 0.68, 95% CrI 0.50–0.91), brexpiprazole (OR 0.69, 95% CrI 0.55–0.86), and cariprazine (OR 0.61, 95% CrI 0.46–0.82) were worse than the placebo. With regards to tolerability, only olanzapine (OR 0.51, 95% CrI 0.25–1.07) and risperidone (OR 0.48, 95% CrI 0.10–2.21) showed no significant differences compared with placebo. The administration of adjunctive antipsychotics is associated with high effectiveness and low acceptability. Risperidone and aripiprazole are more efficacious and accepted than other atypical antipsychotics.
Late Palaeozoic igneous rock associations in response to subduction, accretion, and final closure of the eastern Palaeo-Asian Ocean play a significant role in understanding the geodynamic evolution of the southeastern Central Asian Orogenic Belt. Previous studies have identified a Permian arc magmatic belt associated with the southward-dipping subduction of the eastern Palaeo-Asian Ocean along the Solonker–Changchun suture zone. The genetic mechanism and associated geodynamic settings are of great importance in deciphering the evolution of the eastern Palaeo-Asian Ocean. This paper presents zircon U–Pb–Hf isotope and whole-rock geochemical analyses for a suite of magmatic rocks including the early Permian diorite porphyrites (ca. 281.0 Ma), andesites (ca. 276 Ma) and rhyolites (ca. 275 Ma) in the Kulun region. The diorite porphyrites and andesites have high SiO2 and total alkali contents, and low MgO contents and Mg no. values, with enrichments in large ion lithophile elements and depletions in high-field-strength elements. These geochemical characteristics, together with low-Sr and high-Yb contents, a weak concave-upward shape of middle rare earth elements and negative Eu anomalies, suggest that these intermediate igneous rocks were generated by partial melting of amphibolitic lower crust at a crustal depth of 30–40 km. The rhyolites have heterogeneous isotopic compositions, with ϵHf(t) values and TDM2 ages of –20.8 to +0.5 and 3578∼1494 Ma, implying that they were likely derived from partial melting of a mixed source dominated by recycled ancient crust with minor juvenile crustal materials. The rhyolites show potassic affinity with relatively high K2O and very low Na2O, which was attributed to liquid immiscibility of felsic magma and subsequent limited fractional crystallization of plagioclase. The regional igneous associations, metamorphic events, and coeval sedimentary rocks along the Solonker–Changchun suture zone indicate that the early Permian igneous rocks were formed in an active continental arc environment in response to southward subduction of the eastern Palaeo-Asian Ocean.
The aging population is now a global challenge, and impaired walking ability is a common feature in the elderly. In addition, some occupations such as military and relief workers require extra physical help to perform tasks efficiently. Robotic hip exoskeletons can support ambulatory functions in the elderly and augment human performance in healthy people during normal walking and loaded walking by providing assistive torque. In this review, the current development of robotic hip exoskeletons is presented. In addition, the framework of actuation joints and the high-level control strategy (including the sensors and data collection, the way to recognize gait phase, the algorithms to generate the assist torque) are described. The exoskeleton prototypes proposed by researchers in recent years are organized to benefit the related fields realizing the limitations of the available robotic hip exoskeletons, therefore, this work tends to be an influential factor with a better understanding of the development and state-of-the-art technology.