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Abstract Transcription elongation, especially RNA polymerase II (Pol II) pause-release, is less studied than transcription initiation in regulating gene expression during meiosis. It is also unclear how transcription elongation interplays with transcription initiation. Here, we show that depletion of NKAPL, a testis-specific protein distantly related to RNA splicing factors, causes male infertility in mice by blocking the meiotic exit and downregulating haploid genes. NKAPL binds to promoter-associated nascent transcripts and co-localizes with DNA-RNA hybrid R-loop structures at GAA-rich loci to enhance R-loop formation and facilitate Pol II pause-release. NKAPL depletion prolongs Pol II pauses and stalls the SOX30/HDAC3 transcription initiation complex on the chromatin. Genetic variants in NKAPL are associated with azoospermia in humans, while mice carrying an NKAPL frameshift mutation (M349fs) show defective meiotic exit and transcriptomic changes similar to NKAPL depletion. These findings identify NKAPL as an R-loop-recognizing factor that regulates transcription elongation, which coordinates the meiotic-to-postmeiotic transcriptome switch in alliance with the SOX30/HDAC3-mediated transcription initiation.

Hemihydrate phosphogypsum (HPG), obtained as a cementitious material from the dewatering of phosphogypsum, can be widely used in the preparation of construction materials owing to its low cost and environmental friendliness. However, current reports on HPG mainly focus on hydration behavior, mechanical properties, and durability, and there are few studies focusing on the enhancement of HPG toughness. In this work, glass fibers (GF) and fly ash (FA), as composite reinforcement, were mixed with HPG during its preparation to obtain eco-friendly, high-toughness gypsum. The workability, mechanical, microstructural, financial and environmental properties of the HPG-based composites with different GF volume dosages (0, 0.5, 1.0, and 1.5 vol%) and FA weight percentages (0, 10, 20, and 30 wt%) were comparatively investigated. The results show that the addition of an appropriate amount of FA can improve the interface transition zone between GF and the matrix and effectively increase the flexural strength and toughness of the composites. For the optimal mixture containing 1.5 vol% GF and 20 wt% FA, the flexural strength and toughness were 50.7% and 82.2% higher, respectively, than those of the mixture without FA and 99.2% and 675.3% higher, respectively, than those of the control sample (without GF and FA). Cost-benefit and environmental impact analyses also indicated that this composite was the most economical and environmentally friendly. Thus, this work provides an effective approach to achieve the high-value utilization of two major industrial by-products.

In this paper, a three-layer structure of silver particle (AgNP)-dielectric-metal is proposed and constructed based on the characteristics of AgNPs that can excite LSPR (Localized Surface Plasmon Resonance) in free space. In order to overcome the problem of AgNPs easily oxidizing in the air, this paper synthesizes AgNPs using the improved Tollens method and effectively suppresses the coffee-ring effect by changing the solution evaporation conditions, so that the distribution of AgNPs in the deposition area is relatively uniform. The structure proposed in this paper takes advantage of the flexibility of nanoparticle application. The AgNPs deposited on the dielectric layer can effectively localize energy and regulate the LSPR of the device well. The structure can not only achieve precise regulation of the LSPR resonance peak of AgNPs but also can be used as a SERS substrate.

Non-invasive/minimally invasive continuous monitoring of blood glucose and blood glucose administration have a high impact on chronic disease management in diabetic patients, but the existing technology is yet to achieve the above two purposes at the same time. Therefore, this study proposes a microfluidic microneedle patch based on 3D printing technology and an integrated control system design for blood glucose measurement, and a drug delivery control circuit based on a 555 chip. The proposed method provides an improved preparation of a PVA-PEG-MoS2 nanosheet hydrogel, making use of its dielectric properties to fabricate a microcapacitor and then embedding it in a microfluidic chip. When MoS2 nanosheets react with interstitial liquid glucose (and during the calibration process), the permittivity of the hydrogel is changed, resulting in changes in the capacitance of the capacitor. By converting the capacitance change into the square-wave period change in the output of the 555 chip with the control circuit design accordingly, the minimally invasive continuous measurement of blood glucose and the controlled release of hypoglycemic drugs are realized. In this study, the cross-linking structure of MoS2 nanosheets in hydrogel was examined using infrared spectroscopy and scanning electron microscopy (SEM) methods. Moreover, the critical doping mass fraction of MoS2 nanosheets was determined to be 2% via the measurement of the dielectric constant. Meanwhile, the circuit design and the relationship between the pulse cycle and glucose concentration is validated. The results show that, compared with capacitors in series, the microcapacitors embedded in microfluidic channels can be connected in parallel to obtain better linearized blood glucose measurement results.

In order to address the complexity of fracture damage behavior in metallic materials during service, the thermography technique was used to analyze the temperature evolution behavior of Q460 steel during cyclic deformation. The microscopic organization and microstructural mechanical properties of the crack tip (CT) region of the specimen were also examined to study the fatigue damage mechanism and crack propagation mechanism of Q460 steel from the perspectives of microstructure and energy evolution. The results showed that under the action of fatigue load, dislocation formation and motion occurred in the specimen, accompanied by energy release, which led to a change in surface temperature. The temperature of the fatigue failure area rapidly increased, leading to the formation of a large number of low-angle grain boundaries (LAGB). The nano-indentation results effectively studied the mechanical properties of the stress field area at the CT and revealed that the fatigue crack propagation process of Q460 steel is a result of the synergistic effect between the variation of grain orientation the crack region and the aggregation of a large number of micro-defects in the work-hardened zone. Based on the fatigue heat generation mechanism and entropy evolution mechanism, the study comprehensively analyzed consistency and differences in the damage mechanisms of Q460 steel under tensile load and fatigue load, employing temperature as a bridge. The research results ensure the safety and reliability of Q460 steel during its operation and provide new insights into the study of fatigue fracture behavior in metallic materials.

BackgroundSerum albumin plays a pivotal role in regulating plasma oncotic pressure and modulating fluid distribution among various body compartments. Previous research examining the association between maternal serum albumin levels and fetal growth yielded limited and inconclusive findings. Therefore, the specific influence of serum albumin on fetal growth remains poorly understood and warrants further investigation.MethodsA retrospective study involved 39200 women who had a singleton live birth at a tertiary-care academic medical center during the period from January 2017 to December 2020. Women were categorized into four groups according to the quartile of albumin concentration during early pregnancy: Q1 group, ≤41.0 g/L; Q2 group, 41.1-42.6 g/L; Q3 group, 42.7-44.3 g/L and Q4 group, >44.3 g/L. The main outcome measures were mid-term estimated fetal weight, birthweight and gestational age. Multivariate linear and logistic regression analysis were performed to detect the independent effect of maternal serum albumin level on fetal growth after adjusting for important confounding variables.ResultsIn the crude analysis, a significant inverse correlation was found between early pregnancy maternal serum albumin levels and fetal growth status, including mid-term ultrasound measurements, mid-term estimated fetal weight, birthweight, and gestational age. After adjustment for a number of confounding factors, mid-term estimated fetal weight, birthweight, and birth height decreased significantly with increasing albumin levels. Compared to the Q2 group, the Q4 group had higher rates of preterm birth (aOR, 1.16; 95% CI, 1.01–1.34), small-for-gestational-age (aOR, 1.27; 95% CI, 1.11–1.45) and low birthweight (aOR, 1.41; 95% CI, 1.18–1.69), and lower rate of large-for-gestational-age (aOR, 0.85; 95% CI, 0.78–0.94). Moreover, to achieve the optimal neonatal outcome, women with higher early pregnancy albumin levels required a greater reduction in albumin levels in later pregnancy stages.ConclusionsA higher maternal serum albumin level during early pregnancy was associated with poor fetal growth, with the detrimental effects becoming apparent as early as the mid-gestation period. These findings provided vital information for clinicians to predict fetal growth status and identify cases with a high risk of adverse neonatal outcomes early on.

Abstract Meteorological conditions and source emissions in grassland areas are quite different from those in urban areas, which significantly impacts the spatiotemporal characteristics of black carbon (BC). To obtain the characteristics of BC in the typical grassland environment in China, continuous observations of BC were carried out in Etuoke Banner, a typical grassland environment in Ordos, from September 8 to December 1, 2022. BC in Etuoke Banner in autumn is 22.4–4667.5 ng m−3, and the average concentration is 456.6 ng m−3, accounting for 2.20% of the mass fraction of PM2.5. BCliquid (BC generated from the combustion of liquid fuels) is the main component of BC (accounting for 79.2%); the average concentration is 361.7 ng m−3. The diurnal variations of BC, BCliquid, and BCsolid (BC generated from the combustion of solid fuels) are bimodal, with peaks at 08:00 and 18:00. The first peak is mainly related to traffic sources, cooking sources, and incomplete combustion of carbon‐containing substances; the second peak may be caused by emissions from residential cooking sources under the influence of meteorological conditions unfavorable to diffusion. The diurnal variation of absorption Ångström exponent (AAE) is unimodal, with the peak at 14:00. With the increase in BC mass concentration, AAE and visibility gradually decreased, wind speed first decreased and then increased, P and RH gradually increased, and the contribution of biomass combustion sources to BC decreased. In contrast, the contribution of traffic sources to BC increased. The evolution characteristics of atmospheric pollutants differed with the increase in BC concentration. The potential sources and affecting areas of BC and PM2.5 are mainly concentrated around Etuoke Banner and can affect the North China Plain after 48 h of transmission.

Abstract Mammalian spermatogenesis shows prominent chromatin and transcriptomic switches in germ cells, but it is unclear how such dynamics are controlled. Here we identify RNA helicase DDX43 as an essential regulator of the chromatin remodeling process during spermiogenesis. Testis-specific Ddx43 knockout mice show male infertility with defective histone-to-protamine replacement and post-meiotic chromatin condensation defects. The loss of its ATP hydrolysis activity by a missense mutation replicates the infertility phenotype in global Ddx43 knockout mice. Single-cell RNA sequencing analyses of germ cells depleted of Ddx43 or expressing the Ddx43 ATPase-dead mutant reveals that DDX43 regulates dynamic RNA regulatory processes that underlie spermatid chromatin remodeling and differentiation. Transcriptomic profiling focusing on early-stage spermatids combined with enhanced crosslinking immunoprecipitation and sequencing further identifies Elfn2 as DDX43-targeted hub gene. These findings illustrate an essential role for DDX43 in spermiogenesis and highlight the single-cell-based strategy to dissect cell-state-specific regulation of male germline development.

Background: Risk factors for invasive fungal infections (IFIs) after chimeric antigen receptor-modified T cells (CAR-T) treatment have been poorly studied. Here we are investigating the risk factors and prognosis of IFIs following CAR-T therapy. Material and Methods: A case-control study was conducted on the medical records of CAR-T patients admitted to our center between June 2018 and December 2020. The case group (32) consisted of patients who developed IFIs within 60 days after CAR-T infusion, while the control group (298) consisted of patients who did not develop IFIs. The Cox Proportional Hazard Regression model was utilized to analyze the risk factors for the occurrence of IFIs, as well as the factors affecting the 1-year survival rate of patients. Result: Cumulatively, 364 patients were included. Inflammatory cytokine release syndrome (CRS) grade (hazard ratio (HR) 2.34 confidential interval (CI)（1.03–5.30) P = 0.042), ventilation (HR 3.23 CI (1.20–8.71) P = 0.020) and lymphocyte deficiency duration (HR 1.06 CI (1.01–1.10) P = 0.015) were associated with IFIs. IFIs (HR 1.12 CI (0.52–2.41) P = 0.767) did not affect a patient's one-year survival, which was associated with lymphocyte deficiency (HR 1.04 CI (1.01–1.07) P = 0.004) and treatment with broad-spectrum antibacterial (HR 1.80 CI (1.03–3.11) P = 0.038) within 30 days prior to CAR-T infusion. Conclusion: There is an increased risk of IFIs in patients with hematologic malignancies due to ventilation, high-grade CRS, and prolonged lymphocyte deficiency within 60 days after CAR-T infusion. Invasive fungal infection was not a risk factor for death within 1 year of CAR-T therapy, while broad-spectrum antibacterial therapy prior to infusion and prolonged lymphocyte deficiency were risk factors.

The energy storage mechanism and manufacturing equipment of sodium-ion batteries (SIBs) and lithium-ion batteries (LIBs) are similar. However, SIBs offer several advantages, such as low cost, abundant resources, environmental friendliness, and high safety. Consequently, they have garnered significant attention. SIBs are poised to be potential replacements for LIBs and represent ideal candidates in the field of large-scale energy storage. Layered transition-metal oxides (TMOs) are considered highly promising cathode materials due to their high average voltage, high specific capacity, and ease of synthesis. This paper provides a review of recent advances in layered TMOs for SIBs, including NaxCoO2, NaxMnO2, NaxFeO2, and their derivatives. Furthermore, the challenges and prospects in the development of layered TMOs are also discussed. It is hoped that this review will assist in the design and preparation of SIBs with superior electrochemical performance and further facilitate their practical application.

Herein, a non-conventional fluorescent polymer (NCFP) was established by coupling in-situ Schiff base reaction with epoxy ring-open polymerization, which were constructed by hyperbranched polyamidoamine (HPAMAM) and bio-based vanillin epoxy monomer with an aldehyde group (MB). The resulting hybrid covalent adaptive networks (HP/MB) could emit strong intrinsic fluorescence due to the non-conjugated fluorescence derived from HPAMAM, and the fluorescence intensity shows a good linear correlation with the crosslink density. Meanwhile, owing to the epoxy-Schiff base hybrid covalent adaptive network, HP/MB exhibit excellent mechanical properties and self-healing that can be monitored in real time by fluorescence imaging. As a representative, HP/MB-3 exhibited a tensile strength up to 76.4 MPa, and achieved 100% repair of the crack within 4 min at 140 °C under 1.5 MPa pressure. Especially, HP/MB-3 also showed strong fluorescence quenching by Fe3+ ion. Based on the above unique properties, the application potential of HP/MB in responsive metal coating were further explored, and the coated sample could exhibit different degree of fluorescence quenching effect at different corrosion stages. Therefore, the NCFP-based HP/MB possesses great application potential in the areas of fluorescent sensors, anti-counterfeiting labels, self-detecting anticorrosive coatings and engineering damage assessment.

The South China Sea westbound typhoon is one of the major weather systems which affected the precipitation on the Yunnan plateau.The study of water vapor transport characteristics is the base to the prediction and analysis of precipitation.The study used 10-year's westbound typhoon cases from 2010 to 2019 and appropriate NCEP reanalysis data.The study showed that： （1） The water vapor transported to Yunnan by the westbound typhoon were mainly via three paths， Eastern path， Southern path and Northern path.The Eastern path contributed most of water vapor， less contributed by the Northern path.The water vapor contributed by the Southern path were mixed water vapor from the Bay of Bengal and South China Sea； （2） Themajority of water vapor were from the Eastern path and the Southern path.The westbound It's a little bit complicated for the Southwest side of the Southern path， as it mixed the water vapor from the Bay of Bengal and South China Sea.

ABSTRACT: Objectives: Bacterial strains that produce New Delhi metal-β-lactamase 1 (NDM-1) are a worldwide health threat. It remains a challenging task to find a potent NDM-1 inhibitor for clinical practice. Methods: Molecular docking and virtual screening of an in-house fungal natural product database for NDM-1 inhibitors were performed. Based on the screening results, the affinity and inhibition ability of potential NDM-1 inhibitors were determined using purified NDM-1. The efficacy of compounds in combination with four β-lactam antibiotics (meropenem, imipenem, ceftriaxone and ampicillin) was evaluated. Morphological changes in Klebsiella pneumoniae ATCC BAA-2146 after treatment with the compounds were visualised by transmission electron microscopy. Results: In silico screening led to the identification of four fungal products as potential NDM-1 inhibitors. Emerione A (1), a methylated polyketide with bicyclo[4.2.0]octene and 3,6-dioxabicyclo[3.1.0]hexane functionalities, has significant activity in cells (Kd = 11.8 ± 0.6 μM; IC50 = 12.1 ± 0.9 μM) and potentiates the activity of meropenem against two kinds of NDM-1-producing Enterobacteriaceae. To the best of our knowledge, emerione A (1) is the second fungal metabolite reported to exhibit NMD-1 inhibitory activity. According to the structural novelty of our database, we also found a new structural compound, asperfunolone A (2), with potential NMD-1 inhibitory activity. Conclusion: Considering the low toxicity of emerione A (1), it may represent a potential lead compound for anti-NDM-1 drug development.

Galls are products of the hyperplasia of host plant structures induced by gall-inducing organisms and have been considered as an extended phenotype of the inducers. There is little evidence regarding the effect of host plants on gall morphology. We hypothesised that the morphology and developmental pattern of galls are different because of the different location of their stimulation, even though two kinds of inducers are close relatives. We observed that horned galls and their leaflets of their host plant, Rhus chinensis required a longer rapid growth stage than fusiform galls and Rhus potaninii leaflets. The distribution of trichomes showed positional dependence. Molecular analysis showed that in the fusiform gall, the target genes that regulate the plastochron of leaflets and serration development were hardly expressed, and CUP-SHAPED COTYLEDON-2 may be a key gene that regulates the formation of the horns. In summary, horned and fusiform galls showed a developmental pattern similar to those of their host plant leaflets. We suggest that the inducing site is important in the morphology and development of galls.

CuZn-based catalysts are widely used in CO2 hydrogenation, which may effectively convert CO2 to methanol and alleviate CO2 emission issues. The precise design of a model catalyst with a clear atomic structure is crucial in studying the relationship between structure and catalytic activity. In this work, a one-pot strategy was used to synthesize CuZn@ZSM-5 catalysts with approximately two Cu atoms and one Zn atom per unit cell. Atomic Cu and Zn species are confirmed to be located in the [54.6.102] and [62.104] tilings, respectively, by using magic-angle spinning nuclear magnetic resonance spectroscopy (MAS NMR), synchrotron X-ray powder diffraction (SXRD) and high-signal-to-noise-ratio annular dark field scanning transmission electron microscopy (High SNR ADF-STEM). Catalytic hydrogenation of CO2 to methanol was used as a model reaction to investigate the activity of the catalyst with confined active species. Compared to the Cu@ZSM-5, Zn@ZSM-5 and their mixture, the CuZn@ZSM-5 catalyst with a close Cu–Zn distance of 4.5 Å achieves a comparable methanol space–time yield (STY) of 92.0 mgmethanol·gcatal−1·h−1 at 533 K and 4 MPa with high stability. This method is able to confine one to three metal atoms in the zeolite channel and avoid migration and agglomeration of the atoms during the reaction, which maintains the stability of the catalyst and provides an efficient way for adjustment of the type and number of metal atoms along with the distances between them in zeolites.

BackgroundStroke is the second leading cause of death worldwide, causing a considerable disease burden. Ischemic stroke is more frequent, but haemorrhagic stroke is responsible for more deaths. The clinical management and treatment are different, and it is advantageous to classify their risk as early as possible for disease prevention. Furthermore, retinal characteristics have been associated with stroke and can be used for stroke risk estimation. This study investigated machine learning approaches to retinal images for risk estimation and classification of ischemic and haemorrhagic stroke.Study designA case-control study was conducted in the Shenzhen Traditional Chinese Medicine Hospital. According to the computerized tomography scan (CT) or magnetic resonance imaging (MRI) results, stroke patients were classified as either ischemic or hemorrhage stroke. In addition, a control group was formed using non-stroke patients from the hospital and healthy individuals from the community. Baseline demographic and medical information was collected from participants' hospital medical records. Retinal images of both eyes of each participant were taken within 2 weeks of admission. Classification models using a machine-learning approach were developed. A 10-fold cross-validation method was used to validate the results.Results711 patients were included, with 145 ischemic stroke patients, 86 haemorrhagic stroke patients, and 480 controls. Based on 10-fold cross-validation, the ischemic stroke risk estimation has a sensitivity and a specificity of 91.0% and 94.8%, respectively. The area under the ROC curve for ischemic stroke is 0.929 (95% CI 0.900 to 0.958). The haemorrhagic stroke risk estimation has a sensitivity and a specificity of 93.0% and 97.1%, respectively. The area under the ROC curve is 0.951 (95% CI 0.918 to 0.983).ConclusionA fast and fully automatic method can be used for stroke subtype risk assessment and classification based on fundus photographs alone.

As an essential part of artificial intelligence, a knowledge graph describes the real-world entities, concepts and their various semantic relationships in a structured way and has been gradually popularized in a variety practical scenarios. The majority of existing knowledge graphs mainly concentrate on organizing and managing textual knowledge in a structured representation, while paying little attention to the multimodal resources (e.g., pictures and videos), which can serve as the foundation for the machine perception of a real-world data scenario. To this end, in this survey, we comprehensively review the related advances of multimodal knowledge graphs, covering multimodal knowledge graph construction, completion and typical applications. For construction, we outline the methods of named entity recognition, relation extraction and event extraction. For completion, we discuss the multimodal knowledge graph representation learning and entity linking. Finally, the mainstream applications of multimodal knowledge graphs in miscellaneous domains are summarized.

Introduction: Monoclonal antibody (mAb) is an important treatment option for cancer patients and has received widespread attention in recent years. In this context, a comparative safety evaluation of mAbs and traditional anticancer drugs in real-world is warranted.Methods: ADR reports submitted to Henan Adverse Drug Reaction Monitoring Center from 2016 to 2020 for individuals taking antineoplastic drugs were included. Data were analyzed with respect to demographic characteristics, disease types, polypharmacy, past history of ADRs, system organ class, name of suspected drugs per ADR report, severity, result, impact on the primary disease, and biosimilars.Results: A total of 15,910 ADR reports related to antineoplastic drugs were collected, 575 (3.61%) cases were related to mAbs. Female had more reports of ADRs than male. The ADRs of non-mAbs mainly occurred in 1–3 days after injection (4,929, 32.15%), whereas those of mAbs mainly occurred on the same day (297, 51.65%). Serious ADRs accounted for 30.26% (n = 174) of mAb-related reports and 34.46% (n = 5,285; four death cases) of non-mAb-related reports, respectively. A total of 495 (86.08%) reports were related to the branded drugs of mAbs. In general, our findings indicate that the female, the population aged 60–79 years, people with a single disease, people who have no ADRs in the past and people who have received treatment regimens were less likely to be affected by the primary disease after receiving mAbs therapy. The signal mining method produced 14 signals, only Sintilimab-Hepatic failure was off-label ADR.Conclusion: This study partly confirmed the safety profile of mAbs. It is unlikely to affect groups such as the female, the population aged 60-79 years, people with a single disease, people who have no ADRs in the past and people who have received treatment regimens. Combined drugs have little effect on the primary disease. By conducting signal mining method, 14 signals were produced, and only one of them was off-label ADR.

Triclosan (TCS) is an antimicrobial agent widely used in personal care products and a potential endocrine disruptor chemical (EDC). TCS can pass through the placental barrier. Any influence of EDCs on epigenetic changes of placenta and embryo may bring profound impact on later health. This study aimed to investigate the effects of TCS exposure on cell proliferation and migration, and the expression of imprinted genes IGF2/H19 and DNA methylation-related enzymes in human placental extravillous trophoblast cell line HTR-8/SVneo. After exposure to TCS levels of 0 (DMSO Control), 10−11, 10−10, 10−9, 10−8, 10−7, 10−6, 10−5, 3 × 10−5, 6 × 10−5, 10−4 M and incubated for up to 36 h, cell proliferation and migration were examined by CCK-8, EdU incorporation assay and wound healing assay; the mRNA levels of IGF2, H19, DNA methyltransferases (Dnmt3a, Dnmt3b and Dnmt1), ten-eleven translocation enzymes (Tet1, Tet2 and Tet3) and IGF2 Receptor (IGF2R) were analyzed by qRT-PCR. The protein levels of IGF2 were measured by Western blot and ELISA. The cell viability turned to decline at TCS treatment of 3 × 10−5 M and above (all p 0.05). TCS treatments below cytotoxicity doses (< 10−5 M) did not significantly alter the mRNA levels of IGF2, Dnmt1, Dnmt3a, Dnmt3b, Tet1, Tet2 and Tet3, compared to DMSO Control treatment (all p > 0.05). The transcription level of H19 was up-regulated by TCS at 3 × 10−5 M. TCS at 10−7 and 6 × 10−5 M increased the protein level of IGF2 in cell supernatant. Our data suggest that high TCS exposure may suppress HTR-8/SVneo cells viability and migration, increase H19 gene expressions and IGF2 protein secretion. The exact mechanism of TCS action in human trophoblast needs further studies.

IntroductionAdverse drug reactions (ADRs) in pediatric cancer patients have not yet received due attention in the world. Antineoplastic drugs are frequently related to ADRs. Few studies focus on the ADR and the intervention measures in pediatric cancer patients.MethodsADR reports submitted to Henan Adverse Drug Reaction Monitoring Center from 2016 to 2020 for individuals aged from birth to 17 years (including 17 years) were included. Data were analyzed with respect to gender, age, disease types, past history of ADR, occurrence time of ADR, polypharmacy, route of administration, off-label drug use, name of suspected drugs per ADR report, and severity of ADR reports.ResultsA total of 431 ADR reports related to antineoplastic drugs in pediatric patients were collected, 31.55% were serious ADRs (SADRs). The median age of patients was six years (inter quartile range, IQR: 3-11), the age groups with higher reporting rates were concentrated in 1-3-year-olds (130). Past history of ADR, occurrence time of ADR and polypharmacy were statistically associated with SADR. Myelosuppression was the most frequent ADR (15.55%), cytarabine was the most frequent drug (26.22%). The signal mining method produced 14 signals, three signals were off-label ADRs.ConclusionsThis study described the characteristics of ADRs in pediatric cancer patients. By conducting signal mining method, three off-label ADRs need further study. We should pay more attention to these ADRs and develop relative management strategies. More researches are needed to achieve a better understanding of the characteristics of ADRs in pediatric cancer patients of China.

Kerria lacca (Kerr) is an important lac insect extensively used in industrial products in the form of resin, wax and dye. The scarce knowledge on molecular markers for K. lacca is a barrier in elucidating genetic information. Our study identified a total of 16,921 single-nucleotide polymorphisms (SNPs), and 6231 insertions and deletions (InDels)—of which, intergenic variation accounted for 41.22% and 56.30%, and exonic variation accounted for 39.10% and 17.46%, of SNPs and InDels, respectively. Observation of SNPs suggested that nucleotide substitution frequency and transition to transversion (Ts/Tv) ratio were highest at the late adult stage, 3.97, compared to at the other stages, with a genome-wide Ts/Tv ratio of 2.95. The maximum number of SNPs, 2853 (16.86%), was identified in chromosome 8, while the lowest, 1126 (6.65%), was identified in chromosome 7. The maximum and minimum numbers of InDels were located on chromosome 1 and 7, with 834 (13.38%) and 519 (8.33%), respectively. Annotation showed that highest numbers of exonic and intergenic SNPs were present at the late adult stage, whereas the maximum number of InDels was found at the larval stage. On the basis of gene function, 47 gene variations were screened and 23 candidate genes were identified in associations with lac production. Concluding work will enhance knowledge on molecular markers to facilitate an increase in lac production in K. lacca as well as other lac insects.

Circular RNA (circRNA) is a novel regulatory non-coding RNA and participates in diverse physiological and pathological processes. However, the structures and molecular mechanisms of circRNAs remain unclear. In this study, taking advantage of openly databases and bioinformatics analysis, we observed lots of internal complementary base-pairing sequences (ICBPS) existed in plenty of circRNAs, especially in extremely long circRNAs (el-circRNAs, > 5,000 nt). The result indicated that circRNA may not be a simple circular structure. In addition, we put forward the hypothesis of “open-close effect” in the transition for specific circRNA from normal state to morbid state. Taken together, our results not only expand the knowledge of circRNAs, but also highlight the potential molecular mechanism of circRNAs.

Abstract Background Chiauranib is a novel orally active multi-target inhibitor that simultaneously inhibits the angiogenesis-related kinases (VEGFR2, VEGFR1, VEGFR3, PDGFRα, and c-Kit), mitosis-related kinase Aurora B, and chronic inflammation-related kinase CSF-1R. This phase I dose-escalation study was to determine the maximum tolerated dose (MTD), safety, pharmacokinetics, and preliminary antitumor activity of chiauranib in patients with refractory advanced solid tumor and lymphoma. Methods Eighteen patients were treated with continuous dosing of chiauranib from 10 to 65 mg once daily in a dose-escalation 3 + 3 design and evaluated in 28-day cycles. Pharmacokinetic profile of plasma chiauranib was analyzed in both single and multiple dose studies. Results Dose-limiting toxicity (DLT) as of grade 3 hypertension occurred in two patients at 65 mg/day, and one dose level below as MTD was 50 mg/day. The most common treatment-related adverse events included fatigue (61.1%), proteinuria (44.4%), hematuria (38.9%), hypothyroidism (38.9%), hypertriglyceridemia (33.3%), and hypertension (33.3%). A linear and dose-dependent pharmacokinetic profile of chiauranib was characterized with rapid absorption and slow elimination feature in both single and multiple dose studies. The accumulative exposure of chiauranib reached the steady state within 8 days and was approximately increased by twofold as those in the single dose study. No complete or partial response was observed, and 12 patients (66.7%) achieved stable disease (SD). Conclusions Chiauranib demonstrated an acceptable safety and favorable pharmacokinetic profile with potential antitumor activity. Several phase Ib/II clinical studies are currently under further investigation. Trial registration NCT, NCT02122809. Registered 25 April 2014

Fluorine-bearing refining slag (FBS) is used to produce axle steel for electric multiple unit vehicles. To avoid environmental pollution caused by fluorine, a fluorine-free ladle furnace slag (FFS) was designed based on an industrial FBS. The effects of main components on the physical and metallurgical properties of slag were investigated via theoretical analysis and laboratory tests. The composition range of components of the designed FFS are w(CaO) = 40–55 wt.%, w(SiO2) = 2–6 wt.%, w(Al2O3) = 30–40 wt.%, w(MgO) = 6–8 wt.%, and w(CaO)/w(Al2O3) = 1.25–1.50. Industrial-scale test results indicate that the FFS has similar deoxidation and desulfurization capabilities to industrial FBS.

Advances in developmental cardiology have increased our understanding of the early aspects of heart differentiation. However, understanding noncoding RNA (ncRNA) transcription and regulation during this process remains elusive. Here, we constructed transcriptomes for both long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) in four important developmental stages ranging from early embryonic to cardiomyocyte based on high-throughput sequencing datasets, which indicate the high stage-specific expression patterns of two ncRNA types. Additionally, higher similarities of samples within each stage were found, highlighting the divergence of samples collected from distinct cardiac developmental stages. Next, we developed a method to identify numerous lncRNA and circRNA regulators whose expression was significantly stage-specific and shifted gradually and continuously during heart differentiation. We inferred that these ncRNAs are important for the stages of cardiac differentiation. Moreover, transcriptional regulation analysis revealed that the expression of stage-specific lncRNAs is controlled by known key stage-specific transcription factors (TFs). In addition, circRNAs exhibited dynamic expression patterns independent from their host genes. Functional enrichment analysis revealed that lncRNAs and circRNAs play critical roles in pathways that are activated specifically during heart differentiation. We further identified candidate TF-ncRNA-gene network modules for each differentiation stage, suggesting the dynamic organization of lncRNAs and circRNAs collectively controlled cardiac differentiation, which may cause heart-related diseases when defective. Our study provides a foundation for understanding the dynamic regulation of ncRNA transcriptomes during heart differentiation and identifies the dynamic organization of novel key lncRNAs and circRNAs to collectively control cardiac differentiation.

This paper presents the design and simulation of a high conversion efficiency betavoltaic battery composed of multiple, alternately stacked layers of silicon p-n junction converters and 63Ni isotope sources. Self-absorption of β particles within sources of different thicknesses and β particle energy deposition in the converters are investigated via Monte Carlo simulation. Optimizing the source thickness and doping concentration in the converter significantly improves the conversion efficiency and maximum output power of the proposed battery in comparison to one with a simple two-layer structure but same volume and source activity. The proposed battery can achieve an overall conversion efficiency of 3.3% and output power of 17.48 nW/mm2 from 5.05 mCi of 63Ni.

Oncodostigma hainanense is an endangered species with extremely small populations due to human activities in China. This study presents the chloroplast genome of the plant by de novo assembly using the whole-genome sequencing data. The size of the complete chloroplast genome was 160,497 bp in length, comprising a large single copy region (LSC) of 89,424 bp, a small single copy region (SSC) 18,948 bp, and inverted repeat regions (IRS) of 26,061 bp. A total of 135 genes, including 85 protein-coding genes, 42 tRNA genes and eight rRNA genes, were predicted from the chloroplast genomes. Among them, 17 genes occur in IRS, containing six protein-coding genes, seven tRNA genes and four rRNA genes. The GC content of O. hainanense was 35.59%. Phylogenetic analysis with seven other species revealed that O. hainanense was clustered with Annona cherimola.

AISI M2 steel was smelted in a 150 kg medium-frequency induction furnace and cast to form round billets with a cross-section diameter of 100 mm via a vertical continuous caster and sand mold. The secondary dendrite arm spacing (λ2), cooling rates, permeability and size and distribution of grains and network carbides of the two billets were studied. The results show that the continuous casting process can effectively decrease the λ2 value, permeability and size of the grains and carbides and improve the distribution of the grains and carbides during solidification. The λ2 values of the billets cast with a sand mold and continuous caster are 37.34 μm and 21.14 μm, respectively, and the cooling rate is 3.6 K·s−1 and 12.0 K·s−1, respectively. The area fractions of carbides at the center of the billets cast with the sand mold and continuous caster are 0.24 and 0.16, respectively, and increase by 27.7% and 25.4%, respectively, compared with their average values. The average grain size of billets cast with the sand mold and continuous caster is 69.4 μm and 50.5 μm, respectively. Compared with the sand mold billet, the grain size at the center of the continuous casting billet is reduced by 25.5%. The relationship between the grain size and cooling rate is presented in this paper.

Transient pressure measurement system applied in an explosion field is usually characterized by non-real-time measurement due to the conflict between quick signal acquisition and limited communication bandwidth. The correct signal acquisition is launched by triggering, but the false triggering often leads to measurement failure due to the fact that the operating status of system cannot be real-time detected in an explosion condition. A distributed wireless measurement system with data extraction technology is proposed in this paper to improve the reliability of transient pressure measurement. A long-time signal acquisition is achieved by mass data storage to eliminate the trigger mode. On the other hand, an effective data segment is extracted by signal identification, which improves the efficiency of data transmission and data processing. A measurement system based on data extraction technology was designed and implemented in an explosion field, and the measurement node was characterized by sampling rate of 1 Msps, data storage of 128 Gb, effective data segment of 512 kW, and Wi-Fi wireless network coverage.

Hypericum japonicum (Guttiferae), a type of annual or perennial herb, has been historically applied to cure infectious hepatitis, acute and chronic hepatitis, gastrointestinal disorder, and internal hemorrhage. In our successive studies on the genus Hypericum, two new α-pyrones termed japopyrones A and B (1 and 2) were isolated from H. japonicum. Their structures and absolute configurations were established by the comprehensive analyses of spectroscopic data, the application of the Single-crystal X-ray diffraction structural analysis, and the experimental electronic circular dichroism (ECD) spectra. Bioactivity screenings suggested that compound 2 possessed the potential inhibition efficacy on lytic replication of Kaposi’s sarcoma associated herpesvirus (KSHV) with an IC50 29.46 μM and a selective index of higher than 6.79, respectively.

Zanthoxylum schinifolium Sieb. et Zucc. (Rutaceae), a dioecious shrub with hooked prickly branches, has been used as folk medicine for the treatment of the common cold, stomach ache, diarrhea, and jaundice in China, Korea, and Japan. In our phytochemical investigations on this genus, a new megastigmane sesquiterpenoid, which is referred to as schinifolenol A (1), was isolated from Z. schinifolium. The stereochemistry was characterized via the analyses of extensive spectra. The absolute configuration was established by the application of a modified Mosher’s experiment and assisted by a time-dependent density functional theory (TD-DFT) on calculated electronic circular dichroism (ECD). Bioactivity screenings showed that compound 1 exhibited a safe hypotoxicity and a better selectivity on anti-Kaposi’s sarcoma associated herpes virus (KSHV).