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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.
Methods:
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.
Results:
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.
Conclusions:
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.
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 subduction model of the Neo-Tethys during the Early Cretaceous has always been a controversial topic, and the scarcity of Early Cretaceous magmatic rocks in the southern part of the Gangdese batholith is the main cause of this debate. To address this issue, this article presents new zircon U–Pb chronology, zircon Hf isotope, whole-rock geochemistry and Sr–Nd isotope data for the Early Cretaceous quartz diorite dykes with adakite affinity in Liuqiong, Gongga. Zircon U–Pb dating of three samples yielded ages of c. 141–137 Ma, indicating that the Liuqiong quartz diorite was emplaced in the Early Cretaceous. The whole-rock geochemical analysis shows that the Liuqiong quartz diorite is enriched in large-ion lithophile elements (LILEs) and light rare-earth elements (LREEs) and is depleted in high-field-strength elements (HFSEs), which are related to slab subduction. Additionally, the Liuqiong quartz diorite has high SiO2, Al2O3 and Sr contents, high Sr/Y ratios and low heavy rare-earth element (HREE) and Y contents, which are compatible with typical adakite signatures. The initial 87Sr/86Sr values of the Liuqiong adakite range from 0.705617 to 0.705853, and the whole-rock ϵNd(t) values vary between +5.78 and +6.24. The zircon ϵHf(t) values vary from +11.5 to +16.4. Our results show that the Liuqiong adakite magma was derived from partial melting of the Neo-Tethyan oceanic plate (mid-ocean ridge basalt (MORB) + sediment + fluid), with some degree of subsequent peridotite interaction within the overlying mantle wedge. Combining regional data, we favour the interpretation that the Neo-Tethyan oceanic crust was subducted at a low angle beneath the Gangdese during the Early Cretaceous.
Noncompressible torso hemorrhage (NCTH) is a major challenge in prehospital bleeding control and is associated with high mortality. This study was performed to estimate medical knowledge and the perceived barriers to information acquisition among health-care workers (HCWs) regarding NCTH in China.
Methods:
A self-administered and validated questionnaire was distributed among 11 WeChat groups consisting of HCWs engaged in trauma, emergency, and disaster rescue.
Results:
A total of 575 HCWs participated in this study. In the knowledge section, the majority (87.1%) denied that successful hemostasis could be obtained by external compression. Regarding attitudes, the vast majority of HCWs exhibited positive attitudes toward the important role of NCTH in reducing prehospital preventable death (90.4%) and enthusiasm for continuous learning (99.7%). For practice, fewer than half of HCWs (45.7%) had heard of NCTH beforehand, only a minority (14.3%) confirmed they had attended relevant continuing education, and 16.3% HCWs had no access to updated medical information. The most predominant barrier to information acquisition was the lack of continuing training (79.8%).
Conclusions:
Knowledge and practice deficiencies do exist among HCWs. Obstacles to update medical information warrant further attention. Furthermore, education program redesign is also needed.
Chronic inflammation exerts pleiotropic effects in the aetiology and progression of chronic obstructive pulmonary disease (COPD). Glucosamine is widely used in many countries and may have anti-inflammatory properties. We aimed to prospectively evaluate the association of regular glucosamine use with incident COPD risk and explore whether such association could be modified by smoking in the UK Biobank cohort, which recruited more than half a million participants aged 40–69 years from across the UK between 2006 and 2010. Cox proportional hazards models with adjustment for potential confounding factors were used to calculate hazard ratios (HR) as well as 95 % CI for the risk of incident COPD. During a median follow-up of 8·96 years (interquartile range 8·29–9·53 years), 9016 new-onset events of COPD were documented. We found that the regular use of glucosamine was associated with a significantly lower risk of incident COPD with multivariable adjusted HR of 0·80 (95 % CI, 0·75, 0·85; P < 0·001). When subgroup analyses were performed by smoking status, the adjusted HR for the association of regular glucosamine use with incident COPD were 0·84 (0·73, 0·96), 0·84 (0·77, 0·92) and 0·71 (0·62, 0·80) among never smokers, former smokers and current smokers, respectively. No significant interaction was observed between glucosamine use and smoking status (Pfor interaction = 0·078). Incident COPD could be reduced by 14 % to 84 % through a combination of regular glucosamine use and smoking cessation.
To assess changes in dietary patterns among youths in China after COVID-19 lockdown.
Design:
This study was based on the COVID-19 Impact on Lifestyle Change Survey (COINLICS), a national retrospective survey established in early May 2020. The questionnaire was distributed through social media platforms. The sociodemographic information and routine dietary patterns before and after lockdown of participants were investigated. t tests and χ2 tests were used to compare the differences in consumption patterns of twelve major food groups and beverages between sex and across educational levels before and after lockdown. Factor analysis was employed to obtain the main dietary patterns.
Settings:
China.
Participants:
A total of 10 082 youths.
Results:
A significant decrease was observed in the average weekly frequency of rice intake, while significant increases were observed in the frequency of intake of wheat products, other staple foods, fish, eggs, fresh vegetables, preserved vegetables, fresh fruit and dairy products (all P values < 0·01). Heterogeneities of average weekly frequency existed between sex and across educational levels to different extents. The three main dietary patterns derived were loaded most heavily on dairy products, rice and wheat products, separately; the rice pattern became more dominant than the wheat products pattern after lockdown. The frequency of sugar-sweetened beverage consumption had decreased, while the frequency of other beverages had increased.
Conclusions:
Our timely survey would inform policymakers and health professionals of these significant changes in youths’ dietary patterns after lockdown, with heterogeneities observed to different extents between sex and across educational levels, for better policy-making and public health practice.
The purpose of the current study was to investigate associations between spicy food intake and serum lipids levels in Chinese rural population.
Design:
Information on spicy food flavour and intake frequency was obtained using a two-item questionnaire survey. Dietary data were collected using a validated thirteen-item FFQ. Fasting blood samples were collected and measured for total cholesterol (TC), TAG, HDL-cholesterol and LDL-cholesterol. Multivariate linear and logistic regression models were employed to examine the relationship between spicy food and serum lipids levels according to the spicy food flavour and intake frequency, respectively.
Setting:
A cross-sectional study in Henan Province.
Participants:
38 238 participants aged 18–79 years old.
Results:
Spicy flavour and intake frequency were consistently associated with decreased TC and non-HDL-cholesterol levels but mildly associated with elevated TAG levels. Each level increment in spicy flavour was inversely associated with high TC (OR: 0·91; 95 % CI 0·88, 0·93) and high non-HDL-cholesterol (OR: 0·88; 95 % CI 0·85, 0·91) but positively associated with high TAG (OR: 1·04; 95 % CI 1·01, 1·07). Similarly, 1-d increment in spicy food intake frequency was also inversely associated with high TC (OR: 0·92; 95 % CI 0·91, 0·94) and high non-HDL-cholesterol (OR: 0·91; 95 % CI 0·89, 0·93) but positively associated with high TAG (OR: 1·04; 95 % CI 1·02, 1·06).
Conclusions:
Spicy food intake was mildly associated with increased risk of abnormal TAG level, significantly associated with decreased risk of abnormal TC and non-HDL levels. Spicy food intake may be contribute to the management of lipid levels.
Late Mesozoic igneous rocks are important for deciphering the Mesozoic tectonic setting of NE China. In this paper, we present whole-rock geochemical data, zircon U–Pb ages and Lu–Hf isotope data for Early Cretaceous volcanic rocks from the Tulihe area of the northern Great Xing’an Range (GXR), with the aim of evaluating the petrogenesis and genetic relationships of these rocks, inferring crust–mantle interactions and better constraining extension-related geodynamic processes in the GXR. Zircon U–Pb ages indicate that the rhyolites and trachytic volcanic rocks formed during late Early Cretaceous time (c. 130–126 Ma). Geochemically, the highly fractionated I-type rhyolites exhibit high-K calc-alkaline, metaluminous to weakly peraluminous characteristics. They are enriched in light rare earth elements (LREEs) and large-ion lithophile elements (LILEs) but depleted in high-field-strength elements (HFSEs), with their magmatic zircons ϵHf(t) values ranging from +4.1 to +9.0. These features suggest that the rhyolites were derived from the partial melting of a dominantly juvenile, K-rich basaltic lower crust. The trachytic volcanic rocks are high-K calc-alkaline series and exhibit metaluminous characteristics. They have a wide range of zircon ϵHf(t) values (−17.8 to +12.9), indicating that these trachytic volcanic rocks originated from a dominantly lithospheric-mantle source with the involvement of asthenospheric mantle materials, and subsequently underwent extensive assimilation and fractional crystallization processes. Combining our results and the spatiotemporal migration of the late Early Cretaceous magmatic events, we propose that intense Early Cretaceous crust–mantle interaction took place within the northern GXR, and possibly the whole of NE China, and that it was related to the upwelling of asthenospheric mantle induced by rollback of the Palaeo-Pacific flat-subducting slab.
This study aimed to evaluate to what extent the different interval times between trophectoderm (TE) biopsy and vitrification influence the clinical outcomes in preimplantation genetic testing (PGT) cycles. Patients who underwent frozen embryo transfer (FET) after PGT between 2015 and 2019 were recruited. In total, 297 cycles with single day 5 euploid blastocyst transfer were included. These cycles were divided into three groups according to the interval times: <1 h group, 1–2 h group, and ≥2 h group. Blastocyst survival, clinical pregnancy, miscarriage, and ongoing pregnancy rates were compared. The results showed that, in PGT-SR cycles, survival rate in the ≥2 h group (96.72%) was significantly lower than in the <1 h group (100%, P = 0.047). The clinical pregnancy rate in the ≥2 h group was 55.93%, significantly lower than in the <1 h group (74.26%, P = 0.017). The ongoing pregnancy rates in the 1–2 h group and the ≥2 h group were 48.28% and 47.46%, respectively, significantly lower than that in the <1 h group (67.33%, P < 0.05). The miscarriage rate in the 1–2 h group was 18.42%, significantly higher than that in the <1 h group (5.33%, P = 0.027). In PGT-A cycles, the clinical pregnancy and ongoing pregnancy rates in the <1 h group were 67.44% and 53.49%, respectively, higher than that in the 1–2 h group (52.94%, 47.06%, P > 0.05) and the ≥2 h group (52.63%, 36.84%, P > 0.05). In conclusion, vitrification of blastocysts beyond 1 h after biopsy significantly influences embryo survival and clinical outcomes and is therefore not recommended.
We carry out direct numerical simulations of turbulent Rayleigh–Bénard convection in a square box with rough conducting plates over the Rayleigh number range $10^7\leqslant Ra\leqslant 10^9$ and the Prandtl number range $0.01\leqslant Pr\leqslant 100$. In Zhang et al. (J. Fluid Mech., vol. 836, 2018, R2), it was reported that while the measured Nusselt number $Nu$ is enhanced at large roughness height $h$, the global heat transport is reduced at small $h$. The division between the two regimes yields a critical roughness height $h_c$, and we now focus on the effects of the Prandtl number ($Pr$) on $h_c$. Based on the variations of $h_c$, we identify three regimes for $h_c(Pr)$. For low $Pr$, thermal boundary layers become thinner with increasing $Pr$. This makes the boundary layers easier to be disrupted by rough elements, leading to the decrease of $h_c$ with increasing $Pr$. For moderate $Pr$, the corner-flow rolls become much more pronounced and suppress the global heat transport via the competition between the corner-flow rolls and the large-scale circulation (LSC). As a consequence, $h_c$ increases with increasing $Pr$ due to the intensification of the corner–LSC competition. For high $Pr$, the convective flow transitions to the plume-controlled regime. As the rough elements trigger much stronger and more frequent plume emissions, $h_c$ again decreases with increasing $Pr$.
The nitrogen-decorated CeO2/reduced graphene oxide nanocomposite (CeO2/N-rGO) was one-step synthesized by a facile hydrothermal technique and applied as counter electrode materials for dye-sensitized solar cells (DSSCs). For comparison, CeO2/rGO and rGO were also synthesized by adjusting corresponding reactants. It was found that the as-synthesized CeO2/N-rGO shows better electrocatalytic activity for triiodide/iodide reduction than that of pure rGO and CeO2/rGO, and a synergistic effect of nitrogen and CeO2 on the rGO sheets was observed. The photoelectric conversion efficiency of DSSCs based on CeO2/N-rGO counter electrode was 3.20%, which is higher than that of CeO2/rGO (2.45%) and rGO counter electrode (1.37%). Furthermore, the synergistic effect of nitrogen and CeO2 on the rGO sheets was also discussed in detail with different CeO2 amount levels. It is believed that this one-step synthetic method is a potential way to synthesize low-cost and efficient rGO-based multiple composited counter electrode materials to replace more expensive Pt.
The Arsenic (+3 oxidation state) methyltransferase (AS3MT) gene has been identified as a top risk gene for schizophrenia in several large-scale genome-wide association studies. A variable number tandem repeat (VNTR) of this gene is the most significant expression quantitative trait locus, but its role in brain activity in vivo is still unknown.
Methods
We first performed a functional magnetic resonance imaging (fMRI) scan of 101 healthy subjects during a memory span task, trained all subjects on an adaptive memory span task for 1 month, and finally performed another fMRI scan after the training. After excluding subjects with excessive head movements for one or more scanning sessions, data from 93 subjects were included in the final analyses.
Results
The VNTR was significantly associated with both baseline brain activation and training-induced changes in multiple regions including the prefrontal cortex and the anterior and posterior cingulate cortex. Additionally, it was associated with baseline brain activation in the striatum and the parietal cortex. All these results were corrected based on the family-wise error rate method across the whole brain at the peak level.
Conclusions
This study sheds light on the role of AS3MT gene variants in neural plasticity related to memory span training.
It is well-known that attention deficit hyperactivity disorder (ADHD) is associated with changes in the dopaminergic system. However, the relationship between central dopaminergic tone and the blood oxygen level-dependent (BOLD) signal during receipt of rewards and penalties in the corticostriatal pathway in adults with ADHD is unclear.
Methods
Single-photon emission computed tomography with [99mTC]TRODAT-1 was used to assess striatal dopamine transporter (DAT) availability. Event-related functional magnetic resonance imaging was conducted on subjects performing the Iowa Gambling Test.
Result
DAT availability was found to be associated with the BOLD response, which was a covariate of monetary loss, in the medial prefrontal cortex (r = 0.55, P = .03), right ventral striatum (r = 0.69, P = .003), and right orbital frontal cortex (r = 0.53, P = .03) in adults with ADHD. However, a similar correlation was not found in the controls.
Conclusions
The results confirmed that dopaminergic tone may play a different role in the penalty-elicited response of adults with ADHD. It is plausible that a lower neuro-threshold accompanied by insensitivity to punishment could be exacerbated by the hypodopaminergic tone in ADHD.
A kind of novel Ni–P gradient coating/stannate conversion film was deposited on AZ91D magnesium alloy (AZ91D alloy) by an integrative method involved stannate conversion and electroless plating. The results indicated that using sodium hypophosphite concentrations varied as 5, 10, 22, 46, and 60 g/L in the bath, the electroless Ni–P gradient coating with typical cell morphologies was successfully prepared, and the structures transited from crystalline → microcrystalline → amorphous were obtained as increasing P content from 3.31 to 12.58 wt%. Furthermore, the corrosion morphologies, polarization curves, and the electrochemical impedance spectroscopy result indicated that the corrosion resistance of AZ91D alloy substrate was significantly improved and the corrosion resistance of Ni–P gradient coating was superior than that of stannate conversion film, which might be attributed to the gradient structure and rising P content with unique function.
The lichen family Ophioparmaceae contains three genera: Boreoplaca, Hypocenomyce and Ophioparma. The genus Hypocenomyce is reported here for the first time for China, being represented by the species Hypocenomyce scalaris which is distributed in south-western China. For the genus Ophioparma, one new species is described in this paper, namely Ophioparma pruinosa Li S. Wang & Y. Y. Zhang sp. nov., which is characterized by a pruinose thallus and the presence of usnic acid. Ophioparma araucariae is also reported as new for the Chinese lichen biota. Previous reports of O. lapponica in China are recognized as misidentifications of O. ventosa. Descriptions, keys and phylograms are provided for these species.
High concentrations of non-esterified fatty acid (NEFA) and β-hydroxybutyrate (BHBA) in cows’ blood caused by ketosis are associated with inflammatory states. We hypothesised that ketosis in postparturient dairy cows would result in altered levels on inflammation-related proteins not only in plasma but also in the milk fat globule membranes (MFGM). Thirty cows were selected from a dairy farm in Heilongjiang, China. Inflammatory milk fat globule membrane proteins were detected using ELISA kits, and a fully automatic biochemical analyser was used to measure the concentrations of BHBA, NEFA, glucose (GLU) and triglyceride (TG) in plasma. MFGM protein from milk of ketotic cows contained significantly different concentrations of acute-phase response proteins (complement C3 (C3), prothrombin (F2), alpha-1-acid glycoprotein (ORM1), inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4), alpha-2-HS-glycoprotein (AHSG), complement C9 (C9), complement regulatory protein variant 4 (CD46)) in comparison with milk from non-ketotic cows. Blood concentrations of C3, complement C9 (C9), tumour necrosis factor α (TNFα), MFGM C3, monocyte differentiation antigen CD14 (CD14) and ORM1 levels were correlated with energy balance. ITIH4 and CD46 increased, and AHSG and ORM1 decreased before the onset of ketosis. These biomarkers offer potential as predictors and monitors of ketosis in at-risk cows.
This study aimed to investigate the impacts of dietary threonine on intestinal immunity and inflammation in juvenile grass carp. Six iso-nitrogenous semi-purified diets containing graded levels of threonine (3·99–21·66 g threonine/kg) were formulated and fed to fishes for 8 weeks, and then challenged with Aeromonas hydrophila for 14 d. Results showed that, compared with optimum threonine supplementation, threonine deficiency (1) decreased the ability of fish against enteritis, intestinal lysozyme activities (except in the distal intestine), acid phosphatase activities, complement 3 (C3) and C4 contents and IgM contents (except in the proximal intestine (PI)), and it down-regulated the transcript abundances of liver-expressed antimicrobial peptide (LEAP)-2A, LEAP-2B, hepcidin, IgZ, IgM and β-defensin1 (except in the PI) (P<0·05); (2) could up-regulate intestinal pro-inflammatory cytokines TNF-α, IL-1β, IL-6, IL-8 and IL-17D mRNA levels partly related to NF-κB signalling; (3) could down-regulate intestinal anti-inflammatory cytokine transforming growth factor (TGF)-β1, TGF-β2, IL-4/13A (not IL-4/13B) and IL-10 mRNA levels partly by target of rapamycin signalling. Finally, on the basis of the specific growth rate, against the enteritis morbidity and IgM contents, the optimum threonine requirements were estimated to be 14·53 g threonine/kg diet (4·48 g threonine/100 g protein), 15.05 g threonine/kg diet (4·64 g threonine/100 g protein) and 15·17 g threonine/kg diet (4·68 g threonine/100 g protein), respectively.
The morphology, chemistry and phylogenetic relationships of Chinese populations
of Bulbothrix are described. Nine species, including two new
species B. mammillaria Y. Y. Zhang & Li S. Wang sp.
nov. and B. lacinia Y. Y. Zhang & Li S. Wang sp.
nov., and two newly recorded for the flora, B. scortella and
B. meizospora, are reported. Bulbothrix
mammillaria can be recognized by the sparse cilia that are reduced to a
bulbate structure and the broad lobes (3–11 mm). Bulbothrix
lacinia differs from other species of the genus by dark brown,
spherical to short-cylindrical isidia and common lacinulae on the upper surface.
Phylogenetic relationships of currently known ITS sequences from
Bulbothrix were inferred to assess the affinities of the
new species. A key to all known species from China is presented.
The role of diffusion tensor tractography (DTT) has become increasingly important in the preoperative mapping of brain white matter. Recently, functional magnetic resonance imaging (fMRI) driven DTT has provided the ability to evaluate the spatial relationship between the corticospinal tract (CST) and motor resection tumor boundaries. The main objective of this study was improvement of the preoperative assessment of the CST in patients with gliomas involving the motor cortical areas.
Methods:
Seventeen patients with gliomas involving motor cortical areas underwent 3 dimensions (3D) T1-weighted imaging for anatomical referencing, using both fMRI and diffusion tensor imaging (DTI). We used the fast-marching tractography (FMT) algorithm to define the 3D connectivity maps within the whole brain using seed points selected in the white matter adjacent to the location of fMRI activation. The target region of interest (ROI) was placed in the cerebral peduncle. Karnofsky performance status (KPS) scores were evaluated for each patient before and after surgery.
Results:
The CST of a total seventeen patients were successfully tracked by choosing seed and target ROI on the path of the fibers. What is more, DTT can indicate preoperatively the possibility for total glioma removal or the maximum extent of surgical resection. The postoperative average KPS score for the seventeen patients enrolled increased by more than 10 points.
Conclusions:
Incorporation of fMRI driven DTT showed a maximum benefit in surgical treatment of gliomas. Our study of the assessment precision should enhance the accuracy of glioma operations with a resulting improvement in postoperative patient outcome.