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Kazal-type serine protease inhibitors (KaSPI) play important roles in insect growth, development, digestion, metabolism and immune defence. In this study, based on the transcriptome of Mythimna separata, the cDNA sequence of MsKaSPI with Kazal domain was uploaded to GenBank (MN931651). Spatial and temporal expression analysis showed that MsKaSPI was expressed at different developmental stages and different tissues, and it was induced by 20-hydroxyecdysone in third-instar larvae of M. separata. After 24 h infection by Beauveria bassiana, the expression level of MsKaSPI and the corresponding MsKaSPI content were significantly up-regulated, being 6.42-fold and 1.91-fold to the control group, respectively, while the activities of serine protease, trypsin and chymotrypsin were inhibited. After RNA interference interfered with MsKaSPI for 6 h, the expression decreased by 73.44%, the corresponding content of MsKaSPI protein decreased by 55.66% after 12 h, and the activities of serine protease and trypsin were significantly enhanced. Meanwhile, both the larval and pupal stages of M. separata were prolonged, the weights were reduced and the number of eggs per female decreased by 181. Beauveria bassiana infection also increased the mortality of MsKaSPI-silenced M. separata by 18.96%. These prove MsKaSPI can not only result in slow growth and low fecundity of M. separata by regulating the activity of related protease, but also participate in the resistance to pathogenic fungi by regulating the serine protease inhibitor content and the activities of related serine protease.
Insulin-like growth factor 1 receptor (IGF1R) is a cell surface receptor, belonging to the tyrosine kinase receptor superfamily. IGF1R plays a role not only in normal cell development but also in malignant transformation, which has become a candidate therapeutic target for the treatment of human cancer. This study aimed to explore insertions and deletions (indels) in IGF1R gene and investigate their association with growth traits in four Chinese cattle breeds (Xianan cattle, Jinnan cattle, Qinchuan cattle and Nanyang cattle). The current paper identified a 28-bp indel by polymerase chain reaction within IGF1R gene. The analysis showed that there was a significant correlation between the locus and the hucklebone width of Nanyang cattle in four periods, in which it was highly correlated at 6, 12 and 18 months. At the age of 6 months, it was also significantly correlated with body height, body weight and body length. Association analysis showed that the locus in Jinnan cattle was extremely significantly correlated with body slanting length and body weight, and significantly correlated with chest circumference. There was no significant correlation between this locus and growth traits of Xianan cattle and Qinchuan cattle. The detected indel in the IGF1R gene was significantly associated with growth traits in Jinnan and Nanyang cattle, and could be used as a molecular marker for growth trait selection.
Based on hubs of neural circuits associated with addiction and their degree centrality (DC), this study aimed to construct the addiction-related brain networks for patients diagnosed with heroin dependence undertaking stable methadone maintenance treatment (MMT) and further prospectively identify the ones at high risk for relapse with cluster analysis.
Sixty-two male MMT patients and 30 matched healthy controls (HC) underwent brain resting-state functional MRI data acquisition. The patients received 26-month follow-up for the monthly illegal-drug-use information. Ten addiction-related hubs were chosen to construct a user-defined network for the patients. Then the networks were discriminated with K-means-clustering-algorithm into different groups and followed by comparative analysis to the groups and HC. Regression analysis was used to investigate the brain regions significantly contributed to relapse.
Sixty MMT patients were classified into two groups according to their brain-network patterns calculated by the best clustering-number-K. The two groups had no difference in the demographic, psychological indicators and clinical information except relapse rate and total heroin consumption. The group with high-relapse had a wider range of DC changes in the cortical−striatal−thalamic circuit relative to HC and a reduced DC in the mesocorticolimbic circuit relative to the low-relapse group. DC activity in NAc, vACC, hippocampus and amygdala were closely related with relapse.
MMT patients can be identified and classified into two subgroups with significantly different relapse rates by defining distinct brain-network patterns even if we are blind to their relapse outcomes in advance. This may provide a new strategy to optimize MMT.
Cognitive impairment is common in late-life depression, which may increase Alzheimer disease (AD) risk. Therefore, we aimed to investigate whether late-life major depressive disorder (MDD) has worse cognition and increases the characteristic AD neuropathology. Furthermore, we carried out a comparison between treatment-resistant depression (TRD) and non-TRD. We hypothesized that patients with late-life depression and TRD may have increased β-amyloid (Aβ) deposits in brain regions responsible for global cognition.
We recruited 81 subjects, including 54 MDD patients (27 TRD and 27 non-TRD) and 27 matched healthy controls (HCs). Neurocognitive tasks were examined, including Mini-Mental State Examination and Montreal Cognitive Assessment to detect global cognitive functions. PET with Pittsburgh compound-B and fluorodeoxyglucose were used to capture brain Aβ pathology and glucose use, respectively, in some patients.
MDD patients performed worse in Montreal Cognitive Assessment (p = 0.003) and had more Aβ deposits than HCs across the brain (family-wise error-corrected p < 0.001), with the most significant finding in the left middle frontal gyrus. Significant negative correlations between global cognition and prefrontal Aβ deposits existed in MDD patients, whereas positive correlations were noted in HCs. TRD patients had significantly more deposits in the left-sided brain regions (corrected p < 0.001). The findings were not explained by APOE genotypes. No between-group fluorodeoxyglucose difference was detected.
Late-life depression, particularly TRD, had increased brain Aβ deposits and showed vulnerability to Aβ deposits. A detrimental role of Aβ deposits in global cognition in patients with late-onset or non-late-onset MDD supported the theory that late-life MDD could be a risk factor for AD.
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.
No studies have reported on how to relieve distress or relax in medical health workers while wearing medical protective equipment in coronavirus disease 2019 (COVID-19) pandemic. The study aimed to establish which relaxation technique, among six, is the most feasible in first-line medical health workers wearing medical protective equipment.
This was a two-step study collecting data with online surveys. Step 1: 15 first-line medical health workers were trained to use six different relaxation techniques and reported the two most feasible techniques while wearing medical protective equipment. Step 2: the most two feasible relaxation techniques revealed by step 1 were quantitatively tested in a sample of 65 medical health workers in terms of efficacy, no space limitation, no time limitation, no body position requirement, no environment limitation to be done, easiness to learn, simplicity, convenience, practicality, and acceptance.
Kegel exercise and autogenic relaxation were the most feasible techniques according to step 1. In step 2, Kegel exercise outperformed autogenic relaxation on all the 10 dimensions among the 65 participants while wearing medical protective equipment (efficacy: 24 v. 15, no space limitation: 30 v. 4, no time limitation: 31 v. 4, no body position requirement: 26 v. 4, no environment limitation: 30 v. 11, easiness to learn: 28 v. 5, simplicity: 29 v. 7, convenience: 29 v. 4, practicality: 30 v. 14, acceptance: 32 v. 6).
Kegel exercise seems a promising self-relaxation technique for first-line medical health workers while wearing medical protective equipment among COVID-19 pandemic.
Flexible electrode is an indispensable component of emerging portable, flexible, and wearable electronic devices. Although various flexible electrodes with different dimensions and functions have been explored, developing a new electrode material with excellent mechanical reliability and superior electrical performance remains a challenge. Here, a graphene-covered Cu composite electrode film with a total thickness of ∼100 nm is successfully fabricated onto a flexible polyimide substrate by means of a series of assembly methods including physical vapor deposition, chemical vapor deposition, and transfer technique. The composite electrode film on the flexible substrate exhibits evidently enhanced tensile strength, monotonic bending, and repeatedly bending fatigue reliability as well as electrical performance compared with that of the bared Cu film electrode. Such excellent mechanical performances are attributed to the role of the graphene coating in suppressing fatigue damage formation and preventing crack advance. It is expected that the chemical vapor-deposited graphene-covered Cu composite electrode would extend the potential ultrathin metal film electrode as the innovative electrode material for the next-generation flexible electronic devices.
Oxidative stress is closely related to metabolic disorders, which can lead to various diseases. Nuclear factor E2-related factor 2 (Nrf2) is a central regulator of oxidative stress. Sodium butyrate (NaB) has been shown to alleviate oxidative stress and insulin resistance, yet how Nrf2 is involved in the action of NaB remains unclear. In the present study, rats were rendered obese by feeding a high-fat diet for 9 weeks. NaB (300 mg/kg), which was gavaged every 2 d for 7 weeks, significantly alleviated high-fat diet-induced oxidative stress and insulin resistance. Additionally, the insulin signalling pathway in the liver was activated by NaB, associated with significant activation of Nrf2, superoxide dismutase and glutathione. Furthermore, hepatic up-regulation of Nrf2 in NaB-treated rats was associated with reduced protein content of histone deacetylase 1 and increased histone H3 acetyl K9 (H3K9Ac) modification on the Nrf2 promoter. The actions of NaB were completely abolished when Nrf2 was knocked down in vitro. Taken together, NaB acts as a histone deacetylase inhibitor to up-regulate Nrf2 expression with enhanced H3K9Ac modification on its promoter. NaB-induced Nrf2 activation stimulates transcription of downstream antioxidant enzymes, thus contributing to the amelioration of high-fat diet-induced oxidative stress and insulin resistance.
Northeastern China is a region of high tick abundance, multiple tick-borne pathogens and likely human infections. The spectrum of diseases caused by tick-borne pathogens has not been objectively evaluated in this region for clinical management and for comparison with other regions globally where tick-transmitted diseases are common. Based on clinical symptoms, PCR, indirect immunofluorescent assay and (or) blood smear, we identified and described tick-borne diseases from patients with recent tick bite seen at Mudanjiang Forestry Central Hospital. From May 2010 to September 2011, 42% (75/180) of patients were diagnosed with a specific tick-borne disease, including Lyme borreliosis, tick-borne encephalitis, human granulocytic anaplasmosis, human babesiosis and spotted fever group rickettsiosis. When we compared clinical and laboratory features to identify factors that might discriminate tick-transmitted infections from those lacking that evidence, we revealed that erythema migrans and neurological manifestations were statistically significantly differently presented between those with and without documented aetiologies (P < 0.001, P = 0.003). Twelve patients (6.7%, 12/180) were co-infected with two tick-borne pathogens. We demonstrated the poor ability of clinicians to identify the specific tick-borne disease. In addition, it is necessary to develop specific laboratory assays for optimal diagnosis of tick-borne diseases.
Nacre-mimetic (PE/TiO2)4 nanolayered composites (NLCs) with the nanocrystalline TiO2 layer thickness less than 30 nm and different thickness ratios of inorganic/organic layers were successfully prepared by using layer-by-layer self-assembly and chemical bath deposition method. Mechanical properties, especially fatigue properties of the NLCs with different thickness ratios were evaluated. The elastic modulus, hardness and fracture toughness, strain amplitude to fatigue limits of the NLCs reached 27.78 ± 5.69 GPa, 1.33 ± 0.31 GPa, and 4.16 ± 0.20 MPa m1/2, respectively. Fatigue performance of the NLCs in the high and low cycle fatigue regimes was optimized by tailoring the thickness ratio of the TiO2/PE layers. The PE/TiO2 NLCs with the larger thickness ratio of ∼3 has the high fatigue limit (the critical strain amplitude of 0.0853%) in the high-cycle fatigue regime, while that with the smaller thickness ratio of ∼1 and ∼0.5 are of the good fatigue strength in the low-cycle fatigue regime. The basic mechanism for the enhanced fatigue performance is elucidated.
We report the utility of whole-genome sequencing (WGS) conducted in a clinically relevant time frame (ie, sufficient for guiding management decision), in managing a Streptococcus pyogenes outbreak, and present a comparison of its performance with emm typing.
A 2,000-bed tertiary-care psychiatric hospital.
Active surveillance was conducted to identify new cases of S. pyogenes. WGS guided targeted epidemiological investigations, and infection control measures were implemented. Single-nucleotide polymorphism (SNP)–based genome phylogeny, emm typing, and multilocus sequence typing (MLST) were performed. We compared the ability of WGS and emm typing to correctly identify person-to-person transmission and to guide the management of the outbreak.
The study included 204 patients and 152 staff. We identified 35 patients and 2 staff members with S. pyogenes. WGS revealed polyclonal S. pyogenes infections with 3 genetically distinct phylogenetic clusters (C1–C3). Cluster C1 isolates were all emm type 4, sequence type 915 and had pairwise SNP differences of 0–5, which suggested recent person-to-person transmissions. Epidemiological investigation revealed that cluster C1 was mediated by dermal colonization and transmission of S. pyogenes in a male residential ward. Clusters C2 and C3 were genomically diverse, with pairwise SNP differences of 21–45 and 26–58, and emm 11 and mostly emm120, respectively. Clusters C2 and C3, which may have been considered person-to-person transmissions by emm typing, were shown by WGS to be unlikely by integrating pairwise SNP differences with epidemiology.
WGS had higher resolution than emm typing in identifying clusters with recent and ongoing person-to-person transmissions, which allowed implementation of targeted intervention to control the outbreak.
Current approaches to food volume estimation require the person to carry a fiducial marker (e.g. a checkerboard card), to be placed next to the food before taking a picture. This procedure is inconvenient and post-processing of the food picture is time-consuming and sometimes inaccurate. These problems keep people from using the smartphone for self-administered dietary assessment. The current bioengineering study presents a novel smartphone-based imaging approach to table-side estimation of food volume which overcomes current limitations.
We present a new method for food volume estimation without a fiducial marker. Our mathematical model indicates that, using a special picture-taking strategy, the smartphone-based imaging system can be calibrated adequately if the physical length of the smartphone and the output of the motion sensor within the device are known. We also present and test a new virtual reality method for food volume estimation using the International Food Unit™ and a training process for error control.
Our pilot study, with sixty-nine participants and fifteen foods, indicates that the fiducial-marker-free approach is valid and that the training improves estimation accuracy significantly (P<0·05) for all but one food (egg, P>0·05).
Elimination of a fiducial marker and application of virtual reality, the International Food Unit™ and an automated training allowed quick food volume estimation and control of the estimation error. The estimated volume could be used to search a nutrient database and determine energy and nutrients in the diet.
In this paper we present new petrological and whole-rock geochemical data for the Palaeoproterozoic metasedimentary rocks in the upper part of the Ji'an Group within the Jiao–Liao–Ji Belt, China, as well as zircon U–Pb age dates and in situ Lu–Hf isotope data. The new data improve our understanding of the original nature of the metasedimentary rocks, further providing insights into their tectonic setting and the evolutionary history of the northern segment of the Jiao–Liao–Ji Belt. The zircons can be divided into two groups, viz., one of magmatic origin and the other of metamorphic origin. Zircon U–Pb dating gave mean or statistical peak ages for the magmatic zircons at 2035, 2082, 2178, 2343–2421, 2451–2545, 2643–2814 and 2923–3446 Ma, and mean peak ages for the metamorphic zircons at 1855 and 1912 Ma, which indicate a maximum depositional age of 2.03 Ga and two-stage metamorphic events at c. 1.91 and 1.85 Ga for the metasedimentary rocks. Geochemical data show that (1) the protoliths of these rocks were mainly sandstones, greywackes and claystones, together with some shales; (2) the main sources of the sedimentary material were Palaeoproterozoic granites and acid volcanic rocks, with minor contributions from Archaean granitic rocks; and (3) the sediments were deposited in an active continental margin setting. Moreover, along the northeastern margin of the Eastern Block of the North China Craton there is evidence of ancient crustal materials as old as 3.76 Ga, and multiple crustal growth events at 3.23–3.05, 2.80–2.65, 2.54–2.45 and 2.28–2.08 Ga.
We designed a clamped beam bending test using a nanoindentation holder with help of transmission electron microscopy (TEM) and focused ion beam specimen fabrication. The microstructure evolution and crack propagation in nanocrystalline TiN were studied by electron imaging and load–displacement measurements during mechanical loading. By measuring the loads under which the crack starts and stops propagating and the time, we obtained the film's fracture toughness using the finite element method and crack propagation speed. Among these, we identified three types of crack propagation pathways, namely bridging, intergranular and a mixed mode of transgranular and intergranular fracture, and the associated microstructure changes. The measured fracture toughness is in agreement with the reported values. Thus, our in situ TEM bending test provides the first direct measurement of fracture toughness in a TEM and a correlation of fracture toughness with fracture toughening mechanisms in nanocrystalline TiN. The method is general and can be applied to other nanocrystalline materials.
Previous studies support Beck's cognitive model of vulnerability to depression. However, the relationship between his cognitive triad and other clinical features and risk factors among those with major depression (MD) has rarely been systematically studied.
The three key cognitive symptoms of worthlessness, hopelessness and helplessness were assessed during their lifetime worst episode in 1970 Han Chinese women with recurrent MD. Diagnostic and other risk factor information was assessed at personal interview. Odds ratios (ORs) were calculated by logistic regression.
Compared to patients who did not endorse the cognitive trio, those who did had a greater number of DSM-IV A criteria, more individual depressive symptoms, an earlier age at onset, a greater number of episodes, and were more likely to meet diagnostic criteria for melancholia, postnatal depression, dysthymia and anxiety disorders. Hopelessness was highly related to all the suicidal symptomatology, with ORs ranging from 5.92 to 6.51. Neuroticism, stressful life events (SLEs) and a protective parental rearing style were associated with these cognitive symptoms.
During the worst episode of MD in Han Chinese women, the endorsement of the cognitive trio was associated with a worse course of depression and an increased risk of suicide. Individuals with high levels of neuroticism, many SLEs and high parental protectiveness were at increased risk for these cognitive depressive symptoms. As in Western populations, symptoms of the cognitive trio appear to play a central role in the psychopathology of MD in Chinese women.
Protein tyrosine phosphatase 1B (PTP1B) is implicated in the negative regulation of the insulin signalling pathway by dephosphorylating the insulin receptor (IR) and IR substrates. Ganodermalucidum has traditionally been used for the treatment of diabetes in Chinese medicine; however, its anti-diabetic potency and mechanism in vivo is still unclear. Our previously published study reported a novel proteoglycan PTP1B inhibitor, named Fudan-Yueyang-Ganoderma lucidum (FYGL) from G. lucidum, with a half-maximal inhibitory concentration (IC50) value of 5·12 (sem 0·05) μg/ml, a protein:polyglycan ratio of 17:77 and 78 % glucose in polysaccharide, and dominant amino acid residues of aspartic acid, glycine, glutamic acid, alanine, serine and threonine in protein. FYGL is capable of decreasing plasma glucose in streptozotocin-induced diabetic mice with a high safety of median lethal dose (LD50) of 6 g/kg. In the present study, C57BL/6 db/db diabetic mice were trialed further using FYGL as well as metformin for comparison. Oral treatment with FYGL in db/db diabetic mice for 4 weeks significantly (P < 0·01 or 0·05) decreased the fasting plasma glucose level, serum insulin concentration and the homeostasis model assessment of insulin resistance. FYGL also controlled the biochemistry indices relative to type 2 diabetes-accompanied lipidaemic disorders. Pharmacology research suggests that FYGL decreases the plasma glucose level by the mechanism of inhibiting PTP1B expression and activity, consequently, regulating the tyrosine phosphorylation level of the IR β-subunit and the level of hepatic glycogen, thus resulting in the improvement of insulin sensitivity. Therefore, FYGL is promising as an insulin sensitiser for the therapy of type 2 diabetes and accompanied dyslipidaemia.
BalB/C neonate mice and adult BalB/C mice were vaccinated using BCG (Bacille Calmette–Guerin). The pathogenic growth characteristics of BCG in in vitro culture on spleen cells (SPC) were observed and changes in induced expression of IFN (interferon)-γ and IL (interleukin)-4 in SPC were detected using the ELISPOT assay. The results showed that a low dose of BCG (2×103 cfu) exerted 100% immunoprotection on 7-day-old neonate mice and a high dose of BCG (4×104 cfu) exerted 75% immunoprotection. A low dose of BCG (2×103 cfu) exerted 67% immunoprotection on 35-day-old mice. It is also shown that Th1-type cell immunity dominated by IFN-γ was enhanced significantly in the neonate mice injected with a low dose of BCG (2×103 cfu), and Th2-type cell immunity dominated by IL-4 was depressed at the same time. IFN-γ and IL-4 induced by a high dosage of BCG (4×104 cfu) in neonate mice were both increased. IFN-γ and IL-4 induced by a low dose of BCG (2×103 cfu) in 35-day-old mice were also increased. The results indicate that there exists a marked correlation between immunoprotection by BCG in mice and both the immunizing dose and age of the immune animals, which might be relevant to the changes induced by BCG on Th1- and Th2-type cell immunity.
Two new high-resolution spectroscopic datasets of the active binary V711 Tau are analyzed here. Using the Least-Squares Deconvolution method, we have derived the time series profiles of V711 Tau with high signal-to-noise ratio, which have been used to reconstruct the starspot patterns for its two components by means of the Doppler imaging code DoTS. The results show that the high latitude spots are main features for the primary, the low latitude spots are clear for the secondary in both of two observing runs, and the starspot pattern changes obviously during one month. The lifetime of intermediate-low latitude spots is shorter than the high latitude spots for the primary, the low latitude spots of the secondary seem to have a longer lifetime.
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