Long QT syndrome (LQTS) is a detrimental arrhythmia syndrome mainly caused by dysregulated expression or aberrant function of ion channels. The major clinical symptoms of ventricular arrhythmia, palpitations and syncope vary among LQTS subtypes. Susceptibility to malignant arrhythmia is a result of delayed repolarisation of the cardiomyocyte action potential (AP). There are 17 distinct subtypes of LQTS linked to 15 autosomal dominant genes with monogenic mutations. However, due to the presence of modifier genes, the identical mutation may result in completely different clinical manifestations in different carriers. In this review, we describe the roles of various ion channels in orchestrating APs and discuss molecular aetiologies of various types of LQTS. We highlight the usage of patient-specific induced pluripotent stem cell (iPSC) models in characterising fundamental mechanisms associated with LQTS. To mitigate the outcomes of LQTS, treatment strategies are initially focused on small molecules targeting ion channel activities. Next-generation treatments will reap the benefits from development of LQTS patient-specific iPSC platform, which is bolstered by the state-of-the-art technologies including whole-genome sequencing, CRISPR genome editing and machine learning. Deep phenotyping and high-throughput drug testing using LQTS patient-specific cardiomyocytes herald the upcoming precision medicine in LQTS.

We firstly report a 2-μm all-fiber nonlinear pulse compressor based on two pieces of normal dispersion fiber (NDF), which enables a high-power scaling ability of watt-level and a high pulse compression ratio of 13.7. With the NDF-based all-fiber nonlinear pulse compressor, the 450-fs laser pulses with a repetition rate of 101.4 MHz are compressed to 35.1 fs, corresponding to a 5.2 optical oscillation cycle at the 2-μm wavelength region. The output average power reaches 1.28 W, which is believed to be the highest value never achieved from the previous 2-μm all-fiber nonlinear pulse compressors with a high pulse repetition rate above 100 MHz. The dynamic evolution of the ultrafast pulse inside the all-fiber nonlinear pulse compressor is numerically analyzed, matching well with the experimental results.

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.

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.

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.

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.

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.

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.