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Previously reported wearable systems for people with Parkinson’s disease (PD) have been focused on the detection of abnormal gait. They suffered from limited accuracy, large latency, poor durability, comfort, and convenience for daily use. Herewith we report an intelligent wearable system (IWS) that can accurately detect abnormal gait in real-time and provide timely cueing for PD patients. The system features novel sensitive, comfortable and durable plantar pressure sensing insoles with a highly compressed data set, an accurate and fast gait algorithm, and wirelessly controlled timely sensory cueing devices. A total of 29 PD patients participated in the first phase without cueing for developing processes of the algorithm, which achieved an accuracy of over 97% for off-line detection of freezing of gait (FoG). In the second phase with cueing, the evaluation of the whole system was conducted with 16 PD subjects via trial and a questionnaire survey. This system demonstrated an accuracy of 94% for real-time detection of FoG and a mean latency of 0.37 s between the onset of FoG and cueing activation. In questionnaire survey, 88% of the PD participants confirmed that this wearable system could effectively enhance walking, 81% thought that the system was comfortable and convenient, and 70% overcame the FoG. Therefore, the IWS makes it an effective, powerful, and convenient tool for enhancing the mobility of people with PD.
Membrane transporters including glucose transporters (GLUTs) are involved in cellular energy supplies, cell metabolism and other vital biological activities. They have also been implicated in cancer proliferation and metastasis, thus they represent an important target in combatting cancer. However, membrane transporters are very difficult to study due to their multispan transmembrane properties. The new computational tool, AlphaFold2, offers highly accurate predictions of three-dimensional protein structures. The glutamine, threonine and tyrosine (QTY) code provides a systematic method of rendering hydrophobic sequences into hydrophilic ones. Here, we present computational studies of native integral membrane GLUTs with 12 transmembrane helical segments determined by X-ray crystallography and CryoEM, comparing the AlphaFold2-predicted native structure to their water-soluble QTY variants predicted by AlphaFold2. In the native structures of the transmembrane helices, there are hydrophobic amino acids leucine (L), isoleucine (I), valine (V) and phenylalanine (F). Applying the QTY code, these hydrophobic amino acids are systematically replaced by hydrophilic amino acids, glutamine (Q), threonine (T) and tyrosine (Y) rendering them water-soluble. We present the superposed structures of native GLUTs and their water-soluble QTY variants. The superposed structures show remarkable similar residue mean square distance values between 0.47 and 3.6 Å (most about 1–2 Å) despite >44% transmembrane amino acid differences. We also show the differences of hydrophobicity patches between the native membrane transporters and their QTY variants. We explain the rationale why the membrane protein QTY variants become water-soluble. Our study provides insight into the differences between the hydrophobic helices and hydrophilic helices, and offers confirmation of the QTY method for studying multispan transmembrane proteins and other aggregated proteins through their water-soluble variants.
Environmental hypoxia exposure causes fertility problems in human and animals. Compelling evidence suggests that chronic hypoxia impairs spermatogenesis and reduces sperm motility. However, it is unclear whether paternal hypoxic exposure affects fertilization and early embryo development. In the present study, we exposed male mice to high altitude (3200 m above sea level) for 7 or 60 days to evaluate the effects of hypoxia on sperm quality, zygotic DNA methylation and blastocyst formation. Compared with age-matched controls, hypoxia-treated males exhibited reduced fertility after mating with normoxic females as a result of defects in sperm motility and function. Results of in vitro fertilization (IVF) experiments revealed that 60 days’ exposure significantly reduced cleavage and blastocyst rates by 30% and 70%, respectively. Immunohistochemical staining of pronuclear formation indicated that the pronuclear formation process was disturbed and expression of imprinted genes was reduced in early embryos after paternal hypoxia. Overall, the findings of this study suggested that exposing male mice to hypoxia impaired sperm function and affected key events during early embryo development in mammals.
Nowadays, automated essay evaluation (AEE) systems play an important role in evaluating essays and have been successfully used in large-scale writing assessments. However, existing AEE systems mostly focus on grammar or shallow content measurements rather than higher-order traits such as ideas. This paper proposes a new formulation of graph-based features for concept maps using word embeddings to evaluate the quality of ideas for Chinese compositions. The concept map derived from the student’s composition is composed of the concepts appearing in the essay and the co-occurrence relationship between the concepts. By utilizing real compositions written by eighth-grade students from a large-scale assessment, the scoring accuracy of the computer evaluation system (named AECC-I: Automated Evaluation for Chinese Compositions—Ideas) is higher than the baselines. The results indicate that the proposed method deepens the construct-relevant coverage of automatic ideas evaluation in compositions and that it can provide constructive feedback for students.
A closed Quaternary saline paleolake, currently still a lake and named Dalangtan after one of its largest sub-basins, has widely distributed sediments in the western Qaidam Basin, NE Tibetan Plateau. Lacustrine salt minerals and fine sediments from this paleolake provide an environmental record for investigating paleoclimatic evolution in the Asian interior. However, detailed continuous Pliocene–Quaternary paleoclimatic records are broadly lacking from the NE Tibetan Plateau owing to poor exposure of the outcrops in section. For this study, we performed a detailed magnetostratigraphic dating and rock magnetic analysis on a 590-m-long core from the SG-5 borehole in the western Qaidam Basin. The results demonstrate that the lacustrine sediments in the SG-5 borehole were deposited more than ~3.0 Ma. Saline minerals began to increase at 1.2 Ma, and the magnetic susceptibility (χ) also changed at that time; the percentage frequency-dependent magnetic susceptibility was relatively low and uniform throughout the whole core. These observations, combined with the χ, pollen, salt ion, and grain-size records from other boreholes, indicate that the western Qaidam Basin and the greater Asian interior had a significant climate transition at 1.2 Ma during an extreme drought.
Coronavirus disease 2019 (COVID-19) is a newly emerged disease with various clinical manifestations and imaging features. The diagnosis of COVID-19 depends on a positive nucleic acid amplification test by real-time reverse transcription-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the clinical manifestations and imaging features of COVID-19 are non-specific, and nucleic acid test for SARS-CoV-2 can have false-negative results. It is presently believed that detection of specific antibodies to SARS-CoV-2 is an effective screening and diagnostic indicator for SARS-CoV-2 infection. Thus, a combination of nucleic acid and specific antibody tests for SARS-CoV-2 will be more effective to diagnose COVID-19, especially to exclude suspected cases.
In present study, we explored the effects and the underlying mechanisms of phospholipase C (PLC) mediating glucose-induced changes in intestinal glucose transport and lipid metabolism by using U-73122 (a PLC inhibitor). We found that glucose incubation activated the PLC signal and U-73122 pre-incubation alleviated the glucose-induced increase in plcb2, plce1 and plcg1 mRNA expression. Meanwhile, U-73122 pre-treatment blunted the glucose-induced increase in sodium/glucose co-transporters 1/2 mRNA and protein expressions. U-73122 pre-treatment alleviated the glucose-induced increase in TAG content, BODIPY 493/503 fluorescence intensity, lipogenic enzymes (glucose 6-phospate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), malic enzyme and fatty acid synthase (FAS)) activity and the mRNA expressions of lipogenic genes and related transcription factors (6pgd, g6pd, fas, acca, srebp1 and carbohydrate response element-binding protein (chrebp)) in intestinal epithelial cells of yellow catfish. Further research found that U-73122 pre-incubation mitigated the glucose-induced increase in the ChREBP protein expression and the acetylation level of ChREBP in HEK293T cells. Taken together, these data demonstrated that the PLC played a major role in the glucose-induced changes of glucose transport and lipid metabolism and provide a new perspective for revealing the molecular mechanism of glucose-induced changes of intestinal glucose absorption, lipid deposition and metabolism.
Narrowband microwave generation with tuneable frequency is demonstrated by illuminating a photoconductive semiconductor switch (PCSS) with a burst-mode fibre laser. The whole system is composed of a high-power linearly polarized burst-mode pulsed fibre laser and a linear-state PCSS. To obtain a high-performance microwave signal, a desired envelope of burst is necessary and a pulse pre-compensation technique is adopted to avoid envelope distortion induced by the gain-saturation effect. Resulting from the technique, homogenous peak power distribution in each burst is ensured. The maximum energy of the laser burst pulse reaches 200 μJ with a burst duration of 100 ns at the average power of 10 W, corresponding to a peak power of 4 kW. When the PCSS is illuminated by the burst-mode fibre laser, narrowband microwave generation with tuneable frequency (0.80–1.12 GHz) is obtained with a power up to 300 W. To the best of the authors’ knowledge, it is the first demonstration of frequency-tuneable narrowband microwave generation based on a fibre laser. The high-power burst-mode fibre laser reported here has great potential for generating high-power arbitrary microwave signals for a great deal of applicable demands such as smart adaptive radar and intelligent high-power microwave systems.
Volcanic tuffs are important in determining the stratigraphic age of sedimentary sequences, which is closely related to the tectonic, sedimentological, geomorphological, palaeoclimatic, and palaeo-ecological evolution of the sequences. However, it may be difficult practically to identify tuffs in stratigraphic sections, especially when they are altered after deposition. In this study, a series of petrographic, mineralogical, and geochemical analyses was deployed in the tuff layers cropping out in the Lunpola Basin of the central Tibetan Plateau, which is a crucial site for studying the dynamics and processes of the Cenozoic uplift of the Tibetan Plateau and its environmental impacts. In these pyroclastic layers, authigenic analcime is the main volcanic glass alteration product. The analcime-bearing samples are Na-enriched, in contrast to the K-abundant magmatic rocks in the central Tibetan Plateau. The distribution patterns of the rare earth elements (REEs) of the bulk analcime-bearing samples are similar to those of the magmatic rocks but different from those of the analcime-poor sediments and analogues of well-mixed upper continental material (e.g. the upper continental crust and post-Archaean Australian average shales). The distinct distributions of Na and REEs among analcime-bearing samples, analcime-poor sediments, and volcanic rocks reveal that analcime formed both from alteration of volcanic material and from mixing processes with non-volcanic sediments. It is proposed, therefore, that the discrimination plot of Na2O/Al2O3-(La/Yb)N may be used to distinguish the analcime-related pyroclastic rocks from the basin sedimentary sequence, and thus it may provide a means of discriminating between various volcanic material and of supporting age dating by tephrochronology in the central Tibetan Plateau.
During the COVID-19 pandemic, the use of telemedicine as a way to reduce COVID-19 infections was noted and consequently deregulated. However, the degree of telemedicine regulation varies from country to country, which may alter the widespread use of telemedicine. This study aimed to clarify the telepsychiatry regulations for each collaborating country/region before and during the COVID-19 pandemic.
We used snowball sampling within a global network of international telepsychiatry experts. Thirty collaborators from 17 different countries/regions responded to a questionnaire on barriers to the use and implementation of telepsychiatric care, including policy factors such as regulations and reimbursement at the end of 2019 and as of May 2020.
Thirteen of 17 regions reported a relaxation of regulations due to the pandemic; consequently, all regions surveyed stated that telepsychiatry was now possible within their public healthcare systems. In some regions, restrictions on prescription medications allowed via telepsychiatry were eased, but in 11 of the 17 regions, there were still restrictions on prescribing medications via telepsychiatry. Lower insurance reimbursement amounts for telepsychiatry consultations v. in-person consultations were reevaluated in four regions, and consequently, in 15 regions telepsychiatry services were reimbursed at the same rate (or higher) than in-person consultations during the COVID-19 pandemic.
Our results confirm that, due to COVID-19, the majority of countries surveyed are altering telemedicine regulations that had previously restricted the spread of telemedicine. These findings provide information that could guide future policy and regulatory decisions, which facilitate greater scale and spread of telepsychiatry globally.
To evaluate the effects of dietary Ca intake and Ca supplementation during pregnancy on low birth weight (LBW) and small for gestational age (SGA) infants.
A birth cohort study was conducted in 2010–2012 at the Gansu Provincial Maternity and Child Care Hospital in Lanzhou, China.
A birth cohort study.
Totally, 9595 pregnant women who came to the hospital for delivery at 20 weeks of gestation or more, and who were 18 years of age or older.
Compared with non-users, Ca supplement users had a reduced risk of LBW infants (OR = 0·77, 95 % CI: 0·63, 0·95) and a reduced risk of nulliparous women giving birth to LBW infants (OR = 0·75, 95 % CI: 0·58, 0·98) (P < 0·05). More specifically, both the use of Ca supplement before conception and during pregnancy (OR = 0·44, 95 % CI: 0·19, 0·99) and during pregnancy only (OR = 0·80, 95 % CI: 0·65, 0·99) had the main effect of reducing risk of nulliparous women giving birth to LBW infants (P < 0·05). There was no association between Ca supplementation and SGA (OR = 0·87, 95 % CI: 0·75, 1·01) (P > 0·05). However, higher dietary Ca intake during pregnancy decreases the risk of both LBW (quartile 2: OR = 0·72, 95 % CI: 0·55, 0·94; quartile 3: OR = 0·68, 95 % CI: 0·50, 0·62) and SGA infants (quartile 2: OR = 0·77, 95 % CI: 0·63, 0·95; quartile 3: OR = 0·71, 95 % CI: 0·57, 0·88, quartile 4: OR = 0·71, 95 % CI: 0·57, 0·88) (P < 0·05).
Ca supplementation and adequate dietary intake of Ca during pregnancy are associated with a decreased risk of LBW infants born to nulliparous women.
Understanding the patterns of treatment response is critical for the treatment of patients with schizophrenia; one way to achieve this is through using a longitudinal dynamic process study design.
This study aims to explore the response trajectory of antipsychotics and compare the treatment responses of seven different antipsychotics over 6 weeks in patients with schizoprenia (trial registration: Chinese Clinical Trials Registry Identifier: ChiCTR-TRC-10000934).
Data were collected from a multicentre, randomised open-label clinical trial. Patients were evaluated with the Positive and Negative Syndrome Scale (PANSS) at baseline and follow-up at weeks 2, 4 and 6. Trajectory groups were classified by the method of k-means cluster modelling for longitudinal data. Trajectory analyses were also employed for the seven antipsychotic groups.
The early treatment response trajectories were classified into a high-trajectory group of better responders and a low-trajectory group of worse responders. The results of trajectory analysis showed differences compared with the classification method characterised by a 50% reduction in PANSS scores at week 6. A total of 349 patients were inconsistently grouped by the two methods, with a significant difference in the composition ratio of treatment response groups using these two methods (χ2 = 43.37, P < 0.001). There was no differential contribution of high- and low trajectories to different drugs (χ2 = 12.52, P = 0.051); olanzapine and risperidone, which had a larger proportion in the >50% reduction at week 6, performed better than aripiprazole, quetiapine, ziprasidone and perphenazine.
The trajectory analysis of treatment response to schizophrenia revealed two distinct trajectories. Comparing the treatment responses to different antipsychotics through longitudinal analysis may offer a new perspective for evaluating antipsychotics.
In this paper, CuCr–Zr alloys prepared by vacuum melting with adding La and Ni elementswere heat-treated and aged, followed by plastic deformation using low-energy cyclic impact tests, to simultaneously improve their mechanical and electrical properties. Results showed that the grain size of the casted Cu–Cr–Zr alloys was significantly reduced after the solid-solution aging and plastic deformation process. There were a lot of dispersed Cr and Cu5Zr precipitates formed in the alloys, and the numbers of dislocations were significantly increased. Accordingly, the hardness was increased from 78 to 232 HV, and the tensile strength was increased from 225 to 691 MPa. Electrical conductivity has not been significantly affected after these processes. The enhancement of overall performance is mainly attributed to the combined effects of solid-solution hardening, fine grain hardening, and precipitation/dislocation strengthening.
Corona Virus Disease 2019 (COVID-19) has presented an unprecedented challenge to the health-care system across the world. The current study aims to identify the determinants of illness severity of COVID-19 based on ordinal responses. A retrospective cohort of COVID-19 patients from four hospitals in three provinces in China was established, and 598 patients were included from 1 January to 8 March 2020, and divided into moderate, severe and critical illness group. Relative variables were retrieved from electronic medical records. The univariate and multivariate ordinal logistic regression models were fitted to identify the independent predictors of illness severity. The cohort included 400 (66.89%) moderate cases, 85 (14.21%) severe and 113 (18.90%) critical cases, of whom 79 died during hospitalisation as of 28 April. Patients in the age group of 70+ years (OR = 3.419, 95% CI: 1.596–7.323), age of 40–69 years (OR = 1.586, 95% CI: 0.824–3.053), hypertension (OR = 3.372, 95% CI: 2.185–5.202), ALT >50 μ/l (OR = 3.304, 95% CI: 2.107–5.180), cTnI >0.04 ng/ml (OR = 7.464, 95% CI: 4.292–12.980), myohaemoglobin>48.8 ng/ml (OR = 2.214, 95% CI: 1.42–3.453) had greater risk of developing worse severity of illness. The interval between illness onset and diagnosis (OR = 1.056, 95% CI: 1.012–1.101) and interval between illness onset and admission (OR = 1.048, 95% CI: 1.009–1.087) were independent significant predictors of illness severity. Patients of critical illness suffered from inferior survival, as compared with patients in the severe group (HR = 14.309, 95% CI: 5.585–36.659) and in the moderate group (HR = 41.021, 95% CI: 17.588–95.678). Our findings highlight that the identified determinants may help to predict the risk of developing more severe illness among COVID-19 patients and contribute to optimising arrangement of health resources.
Dysregulation in hepatic lipid synthesis by excess dietary carbohydrate intake is often relevant with the occurrence of fatty liver; therefore, the thorough understanding of the regulation of lipid deposition and metabolism seems crucial to search for potential regulatory targets. In the present study, we examined TAG accumulation, lipid metabolism-related gene expression, the enzyme activities of lipogenesis-related enzymes, the protein levels of transcription factors or genes involving lipogenesis in the livers of yellow catfish fed five dietary carbohydrate sources, such as glucose, maize starch, sucrose, potato starch and dextrin, respectively. Generally speaking, compared with other carbohydrate sources, dietary glucose promoted TAG accumulation, up-regulated lipogenic enzyme activities and gene expressions, and down-regulated mRNA expression of genes involved in lipolysis and small ubiquitin-related modifier (SUMO) modification pathways. Further studies found that sterol regulatory element binding protein 1 (SREBP1), a key transcriptional factor relevant to lipogenic regulation, was modified by SUMO1. Mutational analyses found two important sites for SUMOylation modification (K254R and K264R) in SREBP1. Mutant SREBP lacking lysine 264 up-regulated the transactivation capacity on an SREBP-responsive promoter. Glucose reduced the SUMOylation level of SREBP1 and promoted the protein expression of SREBP1 and its target gene stearoyl-CoA desaturase 1 (SCD1), indicating that SUMOylation of SREBP1 mediated glucose-induced hepatic lipid metabolism. Our study elucidated the molecular mechanism of dietary glucose increasing hepatic lipid deposition and found that the SREBP-dependent transactivation was regulated by SUMO1 modification, which served as a new target for the transcriptional programmes governing lipid metabolism.
Data on average iodine requirements for the Chinese population are limited following implementation of long-term universal salt iodisation. We explored the minimum iodine requirements of young adults in China using a balance experiment and the ‘iodine overflow’ hypothesis proposed by our team. Sixty healthy young adults were enrolled to consume a sequential experimental diet containing low, medium and high levels of iodine (about 20, 40 and 60 μg/d, respectively). Each dose was consumed for 4 d, and daily iodine intake, excretion and retention were assessed. All participants were in negative iodine balance throughout the study. Iodine intake, excretion and retention differed among the three iodine levels (P < 0·01 for all groups). The zero-iodine balance derived from a random effect model indicated a mean iodine intake of 102 μg/d, but poor correlation coefficients between observed and predicted iodine excretion (r 0·538 for μg/d data) and retention (r 0·304 for μg/d data). As iodine intake increased from medium to high, all of the increased iodine was excreted (‘overflow’) through urine and faeces by males, and 89·5 % was excreted by females. Although the high iodine level (63·4 μg/d) might be adequate in males, the corresponding level of 61·6 μg/d in females did not meet optimal requirements. Our findings indicate that a daily iodine intake of approximately half the current recommended nutrient intake (120 μg/d) may satisfy the minimum iodine requirements of young male adults in China, while a similar level is insufficient for females based on the ‘iodine overflow’ hypothesis.