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Although long-read single-cell RNA isoform sequencing (scISO-Seq) can reveal alternative RNA splicing in individual cells, it suffers from a low read throughput. Here, we introduce HIT-scISOseq, a method that removes most artifact cDNAs and concatenates multiple cDNAs for PacBio circular consensus sequencing (CCS) to achieve high-throughput and high-accuracy single-cell RNA isoform sequencing. HIT-scISOseq can yield >10 million high-accuracy long-reads in a single PacBio Sequel II SMRT Cell 8M. We also report the development of scISA-Tools that demultiplex HIT-scISOseq concatenated reads into single-cell cDNA reads with >99.99% accuracy and specificity. We apply HIT-scISOseq to characterize the transcriptomes of 3375 corneal limbus cells and reveal cell-type-specific isoform expression in them. HIT-scISOseq is a high-throughput, high-accuracy, technically accessible method and it can accelerate the burgeoning field of long-read single-cell transcriptomics.

As an aneuploidy, trisomy is associated with mammalian embryonic and postnatal abnormalities. Understanding the underlying mechanisms involved in mutant phenotypes is broadly important and may lead to new strategies to treat clinical manifestations in individuals with trisomies, such as trisomy 21 [Down syndrome (DS)]. Although increased gene dosage effects because of a trisomy may account for the mutant phenotypes, there is also the possibility that phenotypic consequences of a trisomy can arise because of the presence of a freely segregating extra chromosome with its own centromere, i.e. a ‘free trisomy’ independent of gene dosage effects. Presently, there are no reports of attempts to functionally separate these two types of effects in mammals. To fill this gap, here we describe a strategy that employed two new mouse models of DS, Ts65Dn;Df(17)2Yey/+ and Dp(16)1Yey/Df(16)8Yey. Both models carry triplications of the same 103 human chromosome 21 gene orthologs; however, only Ts65Dn;Df(17)2Yey/+ mice carry a free trisomy. Comparison of these models revealed the gene dosage-independent impacts of an extra chromosome at the phenotypic and molecular levels for the first time. They are reflected by impairments of Ts65Dn;Df(17)2Yey/+ males in T-maze tests when compared with Dp(16)1Yey/Df(16)8Yey males. Results from the transcriptomic analysis suggest the extra chromosome plays a major role in trisomy-associated expression alterations of disomic genes beyond gene dosage effects. This model system can now be used to deepen our mechanistic understanding of this common human aneuploidy and obtain new insights into the effects of free trisomies in other human diseases such as cancers.

In this paper, a spectral collocation method is developed to numerically approximate a class of stochastic differential equations driven by the fractional Brownian motion. The convergence of the proposed method is proved. Numerical simulations are conducted to illustrate the performance of the proposed method in different cases.

Electrochemical reduction of CO2 to value-added chemicals using renewable electricity provides a promising strategy to achieve sustainable fuel production and carbon neutrality. Along with the development of electrocatalysts, flow cells with gas-diffusion electrodes (GDEs) have been used to reach commercially viable current densities for CO2 electrolysis, while the local environment and CO2 mass transport in the electrodes remain to be elucidated. In this review article, we highlight some insights into the microenvironment in the catalyst layer for CO2 electrolysis, including typical mass transport models for CO2 reduction in H-type cells and GDE flow cells, the effect of a hydrophobic microenvironment on CO2 mass transport and catalytic performance, and the formation of a gas/liquid balance and solid–liquid–gas interfaces for CO2 electrolysis. The insights and discussions in this article can provide important guidelines on the design of catalysts, electrodes, and electrolyzers for CO2 electrolysis, as well as other gas-involving electrocatalytic reactions.

Pancreatic ductal adenocarcinoma (PDAC) is a malignancy with poor prognosis due to early metastasis. The aberrant N6-methyladenosine (m6A) RNA modification has emerged as an important mechanism in cancer progression and metastasis, but its role in PDAC remained largely unknown. Here, we demonstrated that an m6A regulator, heterogeneous nuclear ribonucleoprotein C (HNRNPC), modulated alternative splicing events to promote PDAC metastasis. In clinical PDAC tissues, high expression of HNRNPC was correlated with metastasis, resulting in poor prognosis in PDAC patients. Knockdown of HNRNPC significantly reduced PDAC cell invasion in vitro and metastasis in vivo. In contrast, overexpression of HNRNPC provoked malignant phenotypes of PDAC cells. Mechanistically, HNRNPC antagonized the anti-metastatic isoform of TAF8 (TAF8L) but increased the pro-metastatic alternative splicing isoform of TAF8 (TAF8S). Mutation of the m6A-site of TAF8 attenuated the interaction between HNRNPC and TAF8 transcript, leading to the decrease of TAF8S. Furthermore, experimental manipulation of the anti-metastasis splicing isoform TAF8L revealed that splice isoform switching of TAF8 is crucial for PDAC metastasis. In conclusion, our findings demonstrate the essentiality of HNRNPC-mediated alternative splicing events that impinges on metastatic PDAC.

Dielectric ceramics capacitors (DCC) with excellent energy storage performance (ESP) and charge-discharge performance (CDP) is very critical in the field of advanced electronics and power systems. A strategy that improves the ESP of 0.6Ba(Zr0.2Ti0.8)O3-0.4(Na0.5Bi0.5)TiO3 (BZT-NBT) ceramics was proposed via Sr2+ doping. XRD and SEM results confirmed that 0.6(Ba1-xSrx)(Zr0.2Ti0.8)O3-0.4(Na0.5Bi0.5)TiO3 (x = 0, 0.1, 0.2, 0.3, 0.4) (BSZT-NBT) ceramics formed dense and stable perovskite solid solutions. The relaxor ferroelectric (RFE) properties of BSZT-NBT ceramics were also well proved by dielectric behaviors. A large recoverable energy storage density (Wrec) and large efficiency (η) of 3.72 J cm−3 and 94.03 % (x = 0.3) can be simultaneously obtained at 289 kV cm-1. ESP of BSZT-NBT (x = 0.3) ceramics at 180 kV cm-1 exhibit good frequency (1−100 Hz) and temperature (room temperature (RT)-120 °C) stability. BSZT-NBT (x = 0.3) ceramics at 120 kV cm−1 exhibit a prominent power density (PD) and rapid discharge rate (t0.9) of of 37.62 MW cm−3 and 70.6 ns. All evidences confirm that introduction of Sr2+ into A-site of barium titanate-based ceramics could effectively improve ESP.

Forsythiasides are a kind of phenylethanol glycosides existing in Forsythia suspensa (Thunb.) Vahl, which possesses extensive pharmacological activities. According to the different groups connected to the nucleus, forsythiasides can be divided into A-K. In recent years, numerous investigations have been carried out on forsythiasides A, B, C, D, E, and I, which have the effects of cardiovascular protection, anti-inflammation, anti-oxidation, neuroprotection, et al. Mechanistically, forsythiasides regulate toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor kappaB (NF-κB), nuclear factor-erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) and other signaling pathways, as well as the expression of related cytokines and kinases. Further exploration and development may unearth more treatment potential of forsythiasides and provide more evidence for their clinical applications. In summary, forsythiasides have high development and application value.

Proliferative diabetic retinopathy (PDR) is one of the main complications of diabetes, mainly caused by the aberrant proliferation of retinal vascular endothelial cells and the formation of new blood vessels. Traditional Chinese medicines possess great potential in the prevention and treatment of PDR. Bie-Jia-Ruan-Mai-Tang (BJ), a Chinese medicine formula, has a good therapeutic effect on PDR clinically; however, the mechanism of action involved remains unclear. Therefore, we investigated the effect of BJ on PDR through in vitro and in vivo experiments. A diabetic mouse model with PDR was established by feeding a high-fat–high-glucose diet combined with an intraperitoneal injection of streptozotocin (STZ), while high-glucose-exposed human retinal capillary endothelial cells (HRCECs) were employed to mimic PDR in vitro. The in vivo experiments indicated that BJ inhibited the formation of acellular capillaries, decreased the expression of VEGF, and increased the level of ZO-1 in diabetic mice retina. In vitro experiments showed that high glucose significantly promoted cell viability and proliferation. However, BJ inhibited cell proliferation by cycle arrest in the S phase, thus leading to apoptosis; it also increased the production of ROS, decreased the mitochondrial membrane potential, reduced the ATP production, and also reduced the expressions of p-PI3K, p-AKT, and Bcl-xL, but increased the expressions of Bax and p-NF-κB. These results suggest that BJ induces the apoptosis of HRCECs exposed to high glucose through activating the mitochondrial death pathway by decreasing the PI3K/AKT signaling and increasing the NF-κB signaling to inhibit the formation of acellular capillaries in the retina, thus impeding the development of PDR.

Electroreduction of CO2 to formate on Bi-based catalyst is a promising route for CO2 recycling and sustainable fuel production. The use of gas-diffusion-electrode (GDE) flow cells has generally imp...

Using a simple solid-state mixed oxides method, dense La2Mo2O9 ceramics with a relative density higher than 94% were prepared at relatively low sintering temperatures (

Hematite is a prospective semiconductor in photoelectrochemical (PEC) water oxidation field due to its suitable bandgap for the solar spectrum absorption. Nevertheless, the low transfer and separation efficiency of the charge carriers are restricted by its diffusion length of hole which is 2–4 nm and further reduce the PEC performance. Here, we report an innovative method, by introducing nanocavities into the α-Fe2O3 nanorod arrays photoanodes through helium ions implantation, to improve the charge carriers' transfer and separation efficiency and further to enhance water oxidation performance. The result indicates that, the photocurrent density of nanocavities embedded α-Fe2O3 photoanode (S2-A sample) reaches 1.270 mA/cm2 at 1.6 V vs. RHE which is 1-fold higher than that of the pristine α-Fe2O3 (0.688 mA/cm2) and the photocurrent density of S2-A sample reaches 0.652 mA/cm2 at 1.23 V vs. RHE. In this work, the ion implantation combined with post annealing method is found to be a valid method to improve the photoelectrochemical performance, and it also can be further used to modify the other semiconductor photoelectrodes materials.

Electrochemical reduction of N2 to NH3 under ambient conditions can enable an alternative approach for sustainable, distributed production of NH3 when powered by renewable electricity. However, the...

Electrochemical reduction of nitrate (NO3-) to ammonia (NH3) provides a promising route for recycling nitrate from wastewater to balance the nitrogen cycle and sustainable production of ammonia. Among various catalytic materials for NO3- electroreduction, Cu shows a favorable selectivity to NH3. However, Cu can be easily oxidized, while the effect of the Cu oxidation state on NO3- reduction remains to be elucidated. Here, we report that oxidic Cu formed on a Cu electrode can enhance its activity and selectivity for NO3- reduction to NH3. We first used a polished Cu foil as a model catalyst for NO3- reduction and found that a brief exposure of the Cu electrode to air could increase its yield rate and Faradaic efficiency for NH3 production. The improved catalytic performance was attributed to the formed Cu+ sites that can reduce the energy barrier for NO3- reduction to NH3 and suppress the competing HER reaction. Based on this finding, an oxide-derived Cu (OD-Cu) electrode was prepared by annealing a Cu foil in O2 gas followed by electroreduction, which exhibited superior performance for NO3- reduction to NH3, with a Faradaic efficiency of 92% and a yield rate of 1.1 mmol h-1 cm-2 for NH3 production at -0.15 V versus reversible hydrogen electrode. Moreover, an OD-Cu foam electrode was similarly developed to demonstrate NO3- recycling from a low-concentration NO3- solution, which showed a nearly 100% conversion of NO3- to NH3 using a circulating flow cell.

Down syndrome (DS) is one of the most complex genetic disorders in humans and a leading genetic cause of developmental delays and intellectual disabilities. The mouse remains an essential model organism in DS research because human chromosome 21 (Hsa21) is orthologously conserved with three regions in the mouse genome. Recent studies have revealed complex interactions among different triplicated genomic regions and Hsa21 gene orthologs that underlie major DS phenotypes. Because we do not know conclusively which triplicated genes are indispensable in such interactions for a specific phenotype, it is desirable that all evolutionarily conserved Hsa21 gene orthologs are triplicated in a complete model. For this reason, the Dp(10)1Yey/+;Dp(16)1Yey/+;Dp(17)1Yey/+ mouse is the most complete model of DS to reflect gene dosage effects because it is the only mutant triplicated for all Hsa21 orthologous regions. Recently, several groups have expressed concerns that efforts needed to generate the triple compound model would be so overwhelming that it may be impractical to take advantage of its unique strength. To alleviate these concerns, we developed a strategy to drastically improve the efficiency of generating the triple compound model with the aid of a targeted coat color, and the results confirmed that the mutant mice generated via this approach exhibited cognitive deficits.

As one of the candidates of low-temperature cofired ceramics (LTCC), the sintering behavior, dielectric properties, and silver chemical compatibility of NaCaVO4 were studied. The bulk ceramic samples were densified well at a low sintering temperature of 720 oC with an optimal bulk density of 2.87 g/cm3. Excellent microwave dielectric properties with a low relative permittivity er ~ 9.9, a high quality factor Q × f ~ 31,600 GHz, and a temperature coefficient of resonance frequency τf ~ -66.5 ppm/°C were achieved at 11.5 GHz. The far infrared reflectivity spectra revealed the intrinsic dielectric properties (relative permittivity of 8.34 and dielectric loss of 2.7×10-4) are comparable to the measured values. The absence of chemical reaction between NaCaVO4 and silver at firing temperature, evidenced by X-ray diffraction and energy dispersive spectroscopy indicated the potential prospect for LTCC application. Furthermore, the very low density of NaCaVO4 opens up an avenue for its potential applications in light-weight devices.

Synthesis temperature is always playing a crucial role on the determination of dielectric properties of materials. In this letter, (Bi1.5Zn0.5)(Zn0.5Nb1.5)O7 (BZN) thin film was deposited onto quartz glass substrate by RF magnetron sputtering at room temperature and then post-annealed using rapid thermal processing. Film has been characterized with respect to crystalline phase and surface morphology, by means of X-ray diffraction and atomic force microscopy, suggesting no crystalline structure exists in annealed BZN film after post-annealing. Microwave dielectric properties were measured by split post dielectric resonator technique. After annealing at 150 °C, film showed excellent dielectric permittivity and low loss in microwave frequency range. This result indicates that the annealed BZN thin film has a great potential to be alternative of microwave materials fabricated at low temperature.

Synovial sarcoma is the most common pediatric non-rhabdomyosarcoma soft tissue sarcoma and accounts for about 8–10% of all soft tissue sarcoma in childhood and adolescence. The presence of a chromosomal translocation-associated SS18-SSX-fusion gene is causally linked to development of primary synovial sarcoma. Metastases occur in approximately 50–70% of synovial sarcoma cases with yet unknown mechanisms, which led to about 70–80% mortality rate in five years. To explore the possibilities to investigate metastatic mechanisms of synovial sarcoma, we carried out the first genome-wide search for potential genetic biomarkers and drivers associated with metastasis by comparative mutational profiling of 18 synovial sarcoma samples isolated from four patients carrying the primary tumors and another four patients carrying the metastatic tumors through whole exome sequencing. Selected from the candidates yielded from this effort, we examined the effect of the multiple missense mutations of ADAM17, which were identified solely in metastatic synovial sarcoma. The mutant alleles as well as the wild-type control were expressed in the mammalian cells harboring the SS18-SSX1 fusion gene. The ADAM17-P729H mutation was shown to enhance cell migration, a phenotype associated with metastasis. Therefore, like ADAM17-P729H, other mutations we identified solely in metastatic synovial sarcoma may also have the potential to serve as an entry point for unraveling the metastatic mechanisms of synovial sarcoma.