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Microplastics (MPs) are plastic fragments with particle sizes smaller than 5 mm that have potentially harmful effects on ecosystems and human health. The soil environment is not only the source but also the sink of MPs. Thus, it is necessary to fully understand the pollution and distribution of MPs in soils. In this study, Qinghai Province, northeast of the Qinghai–Tibet Plateau, was selected as the research area, and 22 soil samples were collected and analyzed to study the levels and distribution characteristics of MPs in grassland soils. MPs were obtained from the soils by using density separation, and a laser confocal micro Raman spectrometer was used for MP identification. The results showed that MPs were detected in all of the soil samples. The total abundances of MPs ranged from 1125 to 1329 items/kg, with a mean abundance of 1202 items/kg. Various types, shapes, sizes, and colors of MPs were observed. Polyethylene terephthalate (PET) was the dominant polymer in all the grassland soil samples. The size range of 10–50 μm accounted for 50% of all identified MPs. Pellets were the dominant MP shape, and colored MPs accounted for 64% of all MPs. The results revealed the presence of large quantities of MPs in the grassland soils of remote areas as well. This study can act as a reference for further studies of MPs in terrestrial systems. At the end of the paper, the prospects and suggestions for pollution control by soil MPs are given.

In recent years, single-cell or low-input multi-omics techniques have brought a revolution in the study of pre-implantation embryo development. However, single-cell or low-input proteome research in this field is relatively underdeveloped, due to the limited source of mammalian embryo samples, the objective reality of high abundance zona pellucida proteins, and the lack of hypersensitive proteome technology. Here, a comprehensive solution of ultrasensitive proteome technology was developed for single-cell or low-input mouse embryos. Both deep coverage route and high-throughput route could significantly reduce the starting material and enhance the proteomic depth without any customized instrument. Using the deep coverage route, an average of 2,665 or 4,585 protein groups can be identified from 1 or 20 mouse zygotes respectively. Using the high-throughput route, 300 single mouse zygotes can be analysis in 8 days with an average of 2,371 proteins identified. With its popularization, we believe researchers can choose deep coverage or high-throughput technology routes according to their own conditions.

Cortical neural dynamics mediate information processing for the cerebral cortex, implicated in fundamental biological processes, such as vision and olfaction, in addition to neurological and psychiatric diseases. Spontaneous pain is a key feature of human neuropathic pain. Whether spontaneous pain pushes cortical network into an aberrant state, and if so, whether it can be brought back to a 'normal' operating range to ameliorate pain are unknown. Using a clinically relevant mouse model of neuropathic pain with spontaneous pain-like behavior, we report that orofacial spontaneous pain activated a specific area within the primary somatosensory cortex (S1), displaying synchronized neural dynamics revealed by intravital two-photon calcium imaging. This synchronization was underpinned by local GABAergic interneuron hypoactivity. Pain-induced cortical synchronization could be attenuated by manipulating local S1 networks or clinically effective pain therapies. Specifically, both chemogenetic inhibition of pain-related c-Fos-expressing neurons, and selective activation of GABAergic interneurons, significantly attenuated S1 synchronization. Clinically effective pain therapies including carbamazepine and nerve root decompression could also dampen S1 synchronization. More importantly, restoring a 'normal' range of neural dynamics, through attenuating pain-induced S1 synchronization, alleviated pain-like behavior. These results suggest spontaneous pain pushes S1 regional network into a synchronized state, whereas reversal of this synchronization alleviates pain.

Motivation Cell label annotation is a challenging step in the analysis of single-cell RNA sequencing (scRNA-seq) data, especially for tissue types that are less commonly studied. The accumulation of scRNA-seq studies and biological knowledge leads to several well-maintained cell marker databases. Manually examining the cell marker lists against these databases can be difficult due to the large amount of available information. Additionally, simply overlapping the two lists without considering gene ranking might lead to unreliable results. Thus, an automated method with careful statistical testing is needed to facilitate the usage of these databases. Results We develop a user-friendly computational tool, EasyCellType, which automatically checks an input marker list obtained by differential expression analysis against the databases and provides annotation recommendations in graphical outcomes. The package provides two statistical tests, gene set enrichment analysis and a modified version of Fisher’s exact test, as well as customized database and tissue type choices. We also provide an interactive shiny application to annotate cells in a user-friendly graphical user interface. The simulation study and real-data applications demonstrate favorable results by the proposed method. Availability and implementation https://biostatistics.mdanderson.org/shinyapps/EasyCellType/; https://bioconductor.org/packages/devel/bioc/html/EasyCellType.html. Supplementary information Supplementary data are available at Bioinformatics Advances online.

Continuous biomarkers are common for disease screening and diagnosis. To reach a dichotomous clinical decision, a threshold would be imposed to distinguish subjects with disease from non-diseased individuals. Among various performance metrics for a continuous biomarker, specificity at a controlled sensitivity level (or vice versa) is often desirable for clinical utility since it directly targets where the clinical test is intended to operate. Covariates, such as age, race, and sample collection, could impact the controlled sensitivity level in subpopulations and may also confound the association between biomarker and disease status. Therefore, covariate adjustment is important in such biomarker evaluation. In this paper, we suggest to adopt a parsimonious quantile regression model for the diseased population, locally at the controlled sensitivity level, and assess specificity with covariate-specific control of the sensitivity. Variance estimates are obtained from a sample-based approach and bootstrap. Furthermore, our proposed local model extends readily to a global one for covariate adjustment for the receiver operating characteristic (ROC) curve over the sensitivity continuum. We demonstrate computational efficiency of this proposed method and restore the inherent monotonicity in the estimated covariate-adjusted ROC curve. The asymptotic properties of the proposed estimators are established. Simulation studies show favorable performance of the proposal. Finally, we illustrate our method in biomarker evaluation for aggressive prostate cancer., 28 pages, 2 figures

Research on workplace helping behavior highlights the need for a more balanced perspective that acknowledges both the positive and negative consequences of receiving help. The purpose of this study is to investigate how the mechanisms through which we receive autonomous and dependent help differentially impact recipient task performance, as well as the boundary condition for such effects. Drawing on social information theory, we examined the mediating role of task- and self-focused processes, and the moderating role of perceived prosocial motivation. Through a two-wave and two-source field survey, we collected matched data from 350 employees and their direct supervisors. We examined our hypothesized model with path analysis using Mplus 7.4. Results indicated that receiving autonomous help improved task performance by leading recipients into task-focused processes, and perceived prosocial motivation further strengthened this positive indirect relationship. In contrast, receiving dependent help reduced task performance by eliciting recipients to engage in self-focused processes, and perceived prosocial motivation further augmented this negative indirect relationship. Overall, we spotlight the differential consequences of receiving autonomous and dependent help on recipients and encourage further inquiry about the role of social information processing in the helping literature.

Background Alcohol use disorders result from repeated binge and chronic alcohol consumption followed by negative effects, such as anxiety, upon cessation. This process is associated with the activation of NLRP3 inflammasome-mediated responses. However, whether and how inhibition of the NLRP3 inflammasome alters alcohol intake and anxiety behavior remains unclear. Methods A combination of drinking-in-the-dark and gavage was established in NLRP3-knockout and control mice. Behavior was assessed by open-field and elevated plus maze tests. Binge alcohol drinking was measured at 2 h and 4 h. A 2 h/4 h/24 h voluntary drinking was determined by a two-bottle choice paradigm. Western blotting and ELISA were applied to examine the levels of the NLRP3 inflammasome and- inflammatory factors, such as IL-1β and TNF-α. Nissl staining was used to measure neuronal injury. The electrophysiological method was used to determine glutamatergic transmission in corticostriatal circuits. In vivo optogenetic LTP and LTD were applied to control the function of corticostriatal circuits on the behavior of mice. MCC950 was used to antagonize the NLRP3 inflammasome. Results The binge alcohol intake was decreased in NLRP3 KO mice compared to the control mice. During alcohol withdrawal, NLRP3 deficiency attenuated anxiety-like behavior and neuronal injury in the mPFC and striatum. Moreover, we discovered that glutamatergic transmission to striatal neurons was reduced in NLRP3 KO mice. Importantly, in vivo optogenetic induction of long-term potentiation (LTP) of corticostriatal circuits reversed the effects of NLRP3 deficiency on glutamatergic transmission and anxiety behavior. We also demonstrated that optogenetic induction of LTD decreased anxiety-like behavior and caused a reduction in glutamatergic transmission. Interestingly, NLRP3 deficiency or inhibition (MCC950 injection) attenuated the anxiety-like behavior, but it did not prevent DID + gavage paradigm-induced a persistent enhancement of drinking in a two-bottle choice at 2 and 4 days into withdrawal. Conclusion Our results demonstrate that NLRP3 deficiency decreases binge alcohol intake and anxiety-like behavior through downregulation of glutamatergic transmission in corticostriatal circuits, which may provide an anti-inflammatory target for treating alcohol use disorders.

To investigate the usefulness and effectiveness of a dual beam-current transformer (BCTs) design to monitor and record the beam dosimetry output and energy of pulsed electron FLASH (eFLASH) beams in real-time, and to inform on the usefulness of this design for future eFLASH beam control.Two BCTs are integrated into the head of a FLASH Mobetron system, one located after the primary scattering foil and the other downstream of the secondary scattering foil. The response of the BCTs was evaluated individually to monitor beam output as a function of dose, scattering conditions, and ability to capture physical beam parameters such as pulse width (PW), pulse repetition frequency (PRF), and dose per pulse (DPP), and in combination to determine beam energy using the ratio of the lower-to-upper BCT signal.A linear relationship was observed between the absorbed dose measured on Gafchromic film and the BCT signals for both the upper and lower BCT (RThe dual BCT system integrated within the FLASH Mobetron was shown to be a reliable monitoring system able to quantify accelerator performance and capture all essential physical beam parameters on a pulse-by-pulse basis, and the ratio between the two BCTs was strongly correlated with beam energy. The fast signal readout and processing enables the BCTs to provide real-time information on beam output and energy and is proposed as a system suitable for accurate beam monitoring and control of eFLASH beams.

BackgroundPhysical activity (PA) has been associated with decreased incidence of diabetes. However, few studies have evaluated the influence of occupational and domestic PA on the risk of diabetes with a long-term follow-up. We aimed to examine the association between occupational and domestic PA and the risk of diabetes in a long-term prospective cohort of Chinese adults.MethodsA total of 10,343 adults who were followed up in the China Health and Nutrition Survey from 1997 to 2015 were included in our analysis. Occupational and domestical PA were collected with detailed seven-day data and were converted into metabolic equivalents values. Total PA included occupational, domestic, transportation, and leisure time PA. Diabetes cases were identified by self-reported doctor/health professional diagnosis of diabetes, fasting blood glucose ≥7.0 mmol/L, and glycosylated hemoglobin (HbA1c) ≥6.5%. Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI).ResultsDuring up to 18 years of follow-up (median 10 years), there were 575 diabetes cases documented. Occupational PA accounted for the majority of total PA (68%) in Chinese population, followed by domestic PA (25%). With adjustments for possible covariates, the highest quartiles of total PA (HR, 0.728 [95% CI, 0.570–0.929]) and occupational PA (HR, 0.765 [95% CI, 0.596–0.982]) were significantly associated with a lower risk of diabetes compared with lowest quartiles. The association between domestic PA and the risk of diabetes was insignificant (P >0.05).ConclusionHigher levels of occupational PA were associated with a decreased risk of diabetes risk in the Chinese population. Domestic PA was not associated with the incidence of diabetes.

Skeletal dysplasia is mainly caused by genetic mutations or endocrine abnormality. In this study, a case of disproportionate dwarfism from the Iron Age Beishenjiaqiao cemetery in Xi'an, China is analyzed from the perspective of bioarchaeology. The individual shows disproportionately short stature, with reduced long-bone diaphyseal length especially of both humeri, unfused proximal humerus epiphyses, abnormal development of the shoulder and hip joints, left femoral head necrosis, and unusually gracile left femur and tibia shaft, demonstrating limited mobility and labor capacity. Hypothyroidism, pseudoachondroplasia, and multiple epiphyseal dysplasia are the most likely possible diagnoses although there are other possibilities. By combining the archaeological evidences and historical records, it is speculated that this individual lived a normal life and was well treated during her lifetime. Overall, this rare case concerning dwarfism not only enriches our knowledge of skeletal dysplasia among ancient Chinese in northern China but also demonstrates the humanitarian attitude of ancient society toward the disability. Nanyang Technological University This research is supported by the NAP Start-Up Grant from Nanyang Technological University; the sub-project of the Major Project of the National Social Science Fund of China (Grant No. 19ZDA227); China's national key R & D program (Grant No. 2020YFC1521607); Youth talent innovation team of Zhengzhou University (Grant No.2021-QNTD-05); the sub-project of the Central Plains Civilization Exploration Project in Henan Province (Grant No. 24220078); the research on the roots of Chinese Civilization of Zhengzhou University (Grant No. XKZDJC202006); the open research project of the Key Laboratory of the Ministry of Education of Cultural Heritage Research and Protection Technology of Northwestern University (Grant No. xbdx2019–5–18).

The manipulation of covalent bonds could be directed toward degradable, recyclable, and sustainable materials. However, there is an intrinsic conflict between properties of stability and degradability. Here we report light-controlled formation/scission of three types of covalent bonds (C-N, C-O, and C-S) through photoswitching between equilibrium and nonequilibrium states of dynamic covalent systems, achieving dual benefits of photoaddressable stability and cleavability. The photocyclization of dithienylethene fused aldehyde ring-chain tautomers turns on the reactivity, incorporating/releasing amines, alcohols, and thiols reversibly with high efficiency, respectively. Upon photocycloreversion the system is shifted to kinetically locked out-of-equilibrium form, enabling remarkable robustness of covalent assemblies. Reaction coupling allows remote and directional control of a diverse range of equilibria and further broadens the scope. Through locking and unlocking covalent linkages with light when needed, the utility is demonstrated with capture/release of bioactive molecules, modification of surfaces, and creation of polymers exhibiting tailored stability and degradability/recyclability. The versatile toolbox for photoswitchable dynamic covalent reactions to toggle matters on and off should be appealing to many endeavors.

Here we exquisitely fabricated Cu/ZrO2-dp catalysts with plentiful Cu-ZrO2 interfaces by depositing amorphous ZrO2 onto Cu nanoparticles for the hydrogenation of levulinic acid (LA) to γ-valerolactone (GVL). With the created plentiful Cu-ZrO2 interfaces, the optimal catalyst 3Cu/ZrO2-dp exhibited exceptional catalytic performance under mild reaction conditions, and achieved the highest GVL mass productivity of 266.0 mmol GVL·h−1·g−1 Cu, which was 12.5 and 2.3 times of Cu/ZrO2 catalysts with equivalent Cu loadings prepared by traditional impregnation (3Cu/ZrO2-im) or co-precipitation (3Cu/ZrO2-cp). As far as we know, this GVL mass productivity stood at the highest level compared with those obtained using non-noble metal catalysts under similar reaction conditions. By systematic investigation with multiple characterizations, density functional theory (DFT) calculations, and kinetic studies, it was found that interfacial active centers were created at Cu-ZrO2 interfaces, which contained oxygen vacancies (Ov), negatively charged Cuδ− and partially reduced Zr3+. The Ov favored the adsorption and activation of LA via its ketone group, while negatively charged Cuδ− was able to enhance heterolysis of H2, which resulted in the formation of H+-Cuδ− and Zr3+-H− active species via hydrogen spillover. Also, plentiful acid sites, which derived from coordinatively unsaturated and defective Zr species, generated at Cu-ZrO2 interfaces. With the cooperation of interfacial active centers (Cuδ−-Ov-Zr3+) and acid sites, the fabricated 3Cu/ZrO2-dp with plentiful Cu-ZrO2 interfaces achieved excellent catalytic performance for the hydrogenation of LA to GVL. Hence, the synergistic catalysis of Cu-ZrO2 interfaces provided an effective strategy for designing catalysts with a satisfactory performance for the hydrogenation of LA, which also can be expanded to other hydrodeoxygenation reactions.

Vapor deposition of perovskite solar cells (PSCs) has attracted considerable interest for its dry processing characteristics. However, a two-step sequential vapor deposition method suffers from ineffective conversion of PbI2 to perovskite with reasons still unclear. In this report, we carefully investigated the crystallization orientation of PbI2 films deposited by physical vapor deposition via synchrotron grazing-incidence wide-angle X-ray scattering (GIWAXS) and observed an asymmetric scattering pattern with respect to the qz-axis. The observed oriented morphology and texture hinder the diffusion of MAI molecules in the PbI2 films synthesized by vapor deposition, resulting in over 15% PbI2 remaining at the buried interface after reaction with MAI vapor. As a result, the MAPbI3 synthesized in this way was also highly oriented, especially in the surface layers. Surface fumigation (SF) step was introduced to decrease the orientational anisotropy of PbI2, which successfully breaks the diffusion barriers of MAI molecules by forming a complex layer on the PbI2 surface with polar solvent vapors, like dimethyl sulfoxide or 1,3-dimethyl-2-imidazolidinone. We infer that the SF treatment changes the vapor-solid reaction mechanism from reaction-crystallization to dissolution-recrystallization, which largely promotes the conversion of PbI2 to perovskite. Defects were reduced in perovskite synthesized in this way, and a p-i-n device with 19.56% efficiency was fabricated, which is among the highest efficiencies reported for sequential-vapor-deposited PSCs. Notably, this method enables the fabrication of conformal perovskite layers on uneven substrates. An exemplary PSC showing efficiency of 8.93% was fabricated on a precurved substrate. We believe that the method is applicable to the fabrication of tandem or curved PSCs that are compatible with wearable or building/autocar-integrated photovoltaics in the future.

Disulfiram (DSF), an old anti-alcoholism drug, has emerged as a candidate for drug repurposing in oncology. In exploratory studies on its therapeutic effects, we unexpectedly discovered that DSF increased the phosphorylation of SRC, a proto-oncogene tyrosine-protein kinase elevated in 70% of pancreatic ductal adenocarcinoma (PDAC) cases. This serendipitous and novel finding led to our hypothesis for the current study which proposes DSF may synergize with SRC inhibitors in suppressing PDAC. Human PDAC PANC-1 and BXPC-3 cells were incubated with DSF chelated with copper (Cu2+), SRC inhibitors (PP2 and dasatinib), or transfected with lentiviral short hairpin RNA (shRNA), and their proliferation and apoptosis were analyzed. A xenograft model was employed to verify the in vitro results. The expression of key molecules was detected. DSF significantly inhibited cell proliferation and induced cell apoptosis by increasing the cleavage of poly ADP ribose polymerase (PARP), downregulating Bcl-2 and upregulating p27 in concentration- and time-dependent manners. DSF had little effect on signal transducer and activator of transcription 3 (STAT3) expression but inhibited its phosphorylation. DSF did not alter SRC expression but significantly increased its phosphorylation through upregulating actin filament associated protein 1 like 2 (AFAP1L2). DSF exhibited a synergistic effect, as analyzed by drug coefficient interactions, with either PP2, or dasatinib, or SRC depletion in suppressing PDAC cells in vitro and/or in vivo. The present results indicate DSF is a potential therapeutic drug, particularly when it is combined with SRC inhibitors, and warrant further studies on the pharmacological utility of DSF as a promising adjunct therapy for the treatment of PDAC.

Circular RNA (circRNA), a type of non-coding RNA, has received a great deal of attention with regard to the initiation and progression of tumors. However, the molecular mechanism and function of circRNAs in breast cancer (BC) remain unclear. In the current study, we discovered that hsa_circ_0028899 (also called circRNF10) was significantly reduced in BC tissues, and a higher level of circRNF10 was markedly related to a favorable prognosis. The results of CCK8, colony formation, Transwell, ELISA, and NK cell-mediated cytotoxicity assays indicated that increased circRNF10 expression could significantly repress the proliferation, invasion, and migration of BC cells and enhance the killing efficiency of NK cells against BC cells. According to these biological functions, the possible role and molecular mechanism of circRNF10 in BC cells were further investigated. We used bioinformatics prediction tools to predict circRNF10-bound miRNAs, which were verified by many experimental studies, including FISH, luciferase reporter assays, RIP, and Western blots. These data suggest that circRNF10 serves as a molecular sponge for miR-934 to further regulate PTEN expression and PI3k/Akt/MICA signaling in vitro and tumor growth in vivo. Altogether, these findings reveal that circRNF10 functions as a novel anti-oncogene in BC via sponging miR-934 and suppressing the PI3K/Akt/MICA pathway.

Because of the wide use of information and communication technologies (ICT) in healthcare, medical students' knowledge and skills of modern ICT have been considered essential for their successful learning and future careers. According to Bandura's self-efficacy, enhancing ICT self-efficacy, which might be affected by technology experience, could be a pathway to improving ICT literacy and competence, which should be one focus of medical educationalists. However, there is a lack of suitable measurements of medical students' self-efficacy and a clear understanding of its relationship with technology experience.We conducted a literature review and direct consultation with an expert panel to identify potential items for the ICT self-efficacy scale. Based on the data collected in a survey of 486 first-year medical students in China, the exploratory factor analysis (EFA) was employed to confirm the structure of the final version. Furthermore, we used linear regressions to quantify the association between ICT self-efficacy and technology experience measured by the age of first access to the Internet, the age at first ownership of a personal computer (PC) or a laptop, and that of a smartphone.The EFA results derived 15 items of four factors, with 67.02% of the total variance explained:The ICT scale developed is a reliable and valid task-specific measure to assess ICT Self-Efficacy for medical students. In addition, enhancing students' technology experience might improve their ICT self-efficacy.

Transcription factors (TFs) have the potential function in regulating gene expression. Transcription factor TFAP2C plays important roles in the regulation of post-implantation embryonic development in mice, the reprogramming process, trophectoderm formation and carcinogenesis, but its role in porcine early embryo development remains unclear. This study was conducted to investigate the role of TFAP2C in porcine early embryo development using siRNA cytoplasmic injection. The RNAseq and immunofluorescence staining were performed to detect gene expression, and ChIP and dual luciferase reporter assays were used to elucidate the mechanism. The results showed that the deficiency of TFAP2C could lead to embryonic development disorder. The percentage of the blastocyst in theTFAP2Cknockdown (TFAP2C-KD) group (7.76±1.86%) was significantly decreased compared to the control group (22.92±1.97%) (P**P**etc. were significantly elevated inTFAP2C-KDgroup. Meanwhile, the modification levels of H3K4me3, H3K4me2 and H3K9me3 (P*P**P**TFAP2C-KD group. DNMT1 was mostly expressed in cytoplasm in the control group, while it was mainly expressed in nuclei in theTFAP2C-KD group. In addition, TFAP2C could bind to the promoter region ofSETD2, and the mutation of the TFAP2C binding site resulted in increased activity ofSETD2promoter (P**SETD2, KDM5B etc. and other genes, thereby inhibiting embryonic development. TFAP2C binds to the promoter region ofSETD2and acts as a hindrance protein. This study fills in the deficiency of TFAP2C in porcine early embryo development and provides theoretical support for animal husbandry production and biomedicine.Author SummaryThe correct activation of embryonic genes is required during early embryonic development, and the activation of these genes is subject to strict epigenetic regulation, such as DNA methylation, histone acetylation and methylation, with abnormalities in either leading to birth defects and developmental defects in individuals. TFs have specific binding motifs that regulate gene expression by binding to them. TFAP2C has been studied in post-implantation embryonic development and trophectoderm generation, however, the effect on early embryo development is unknown. Our findings suggest that TFAP2C deficiency disrupts gene expression patterns and leads to abnormal epigenetic modifications, resulting in abnormal embryo development. Furthermore, we found for the first time that TFAP2C can bind to the promoter region ofSETD2, thereby affecting early embryo development in pigs. This indicates the critical role of TFAP2C in early embryo development in pigs on one hand, and also provides theoretical support for livestock production and biomedicine.

GGC repeat expansions within NOTCH2NLC have been identified as the genetic cause of neuronal intranuclear inclusion disease (NIID). To understand the molecular pathogenesis of NIID, here, we established both a transgenic mouse model and a human neural progenitor cells (hNPCs) model. Expression of the NOTCH2NLC with expanded GGC repeats produced widespread intranuclear and perinuclear polyglycine (polyG), polyalanine (polyA), and polyarginine (polyR) inclusions, leading to behavioral deficits and severe neurodegeneration, which faithfully mimicked the clinical and pathological features associated with NIID. Furthermore, conserved alternative splicing events were identified between the NIID mouse and hNPC models, among which was the enrichment of the binding motifs of hnRNPM, an RNA binding protein known as alternative splicing regulator. Expanded NOTCH2NLC-polyG and NOTCH2NLC-polyA could interact with and sequester hnRNPM, while overexpression of hnRNPM could ameliorate the cellular toxicity. These results together suggested that dysfunction of hnRNPM could play an important role in the molecular pathogenesis of NIID.

Background The transcriptional changes around zygotic genome activation (ZGA) in preimplantation embryos are critical for studying mechanisms of embryonic developmental arrest and searching for key transcription factors. However, studies on the transcription profile of porcine ZGA are limited. Results In this study, we performed RNA sequencing in porcine in vivo developed (IVV) and somatic cell nuclear transfer (SCNT) embryo at different stages and compared the transcriptional activity of porcine embryos with mouse, bovine and human embryos. The results showed that the transcriptome map of the early porcine embryos was significantly changed at the 4-cell stage, and 5821 differentially expressed genes (DEGs) in SCNT embryos failed to be reprogrammed or activated during ZGA, which mainly enrichment to metabolic pathways. c-MYC was identified as the highest expressed transcription factor during ZGA. By treating with 10,058-F4, an inhibitor of c-MYC, the cleavage rate (38.33 ± 3.4%) and blastocyst rate (23.33 ± 4.3%) of porcine embryos were significantly lower than those of the control group (50.82 ± 2.7% and 34.43 ± 1.9%). Cross-species analysis of transcriptome during ZGA showed that pigs and bovines had the highest similarity coefficient in biological processes. KEGG pathway analysis indicated that there were 10 co-shared pathways in the four species. Conclusions Our results reveal that embryos with impaired developmental competence may be arrested at an early stage of development. c-MYC helps promote ZGA and preimplantation embryonic development in pigs. Pigs and bovines have the highest coefficient of similarity in biological processes during ZGA. This study provides an important reference for further studying the reprogramming regulatory mechanism of porcine embryos during ZGA.

Cyclobutane pyrimidine dimers (CPDs) are the main mutagenic DNA photoproducts caused by ultraviolet B (UVB) radiation and represent the major cause of photoaging and skin carcinogenesis. CPD photolyase can efficiently and rapidly repair CPD products. Therefore, they are candidates for the prevention of photodamage. However, these photolyases are not present in placental mammals. In this study, we produced a recombinant photolyase-thymine (rPHO) from Thermus thermophilus (T. thermophilus). The rPHO displayed CPD photorepair activity. It prevented UVB-induced DNA damage by repairing CPD photoproducts to pyrimidine monomers. Furthermore, it inhibited UVB-induced ROS production, lipid peroxidation, inflammatory responses, and apoptosis. UVB-induced wrinkle formation, epidermal hyperplasia, and collagen degradation in mice skin was significantly inhibited when the photolyase was applied topically to the skin. These results demonstrated that rPHO has promising protective effects against UVB-induced photodamage and may contribute to the development of anti-UVB skin photodamage drugs and cosmetic products.

Deficits in responding to joint attention (RJA) are early symptoms of autism spectrum disorder (ASD). Currently, no automated tools exist for identifying and quantifying RJA behaviors. A few eye tracking studies have investigated RJA in ASD children but have produced conflicting results. In addition, little is known about the trajectory of RJA development through developmental age. Here, a new video was designed including 12 clips of an actor pointing to or looking at an object. Eye tracking technology was used to monitor RJA in three groups: 143 ASD children assessed with the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) (4–7 years old), 113 age- and gender-matched typically developing children (TDC), and 43 typically developing adults (TDA) (19–32 years old). RJAfinder was developed in R and MATLAB to quantify RJA events from the eye tracking data. RJA events were compared among the three groups. Spearman correlation coefficients between total number of RJA events in ASD and the Social Responsiveness Scale (SRS) scores were calculated. A logistic regression model was built using the average valid sampling rate and the total number of RJA events as two predictive variables to classify ASD and TDC groups. ASD children displayed statistically significantly less RJA events than the TDC and TDA groups with medium-to-large-sized effects. ASD and TDC children both displayed more RJA events in response to pointing stimuli than to looking stimuli. Our logistic regression model predicted ASD tendency with 0.76 accuracy in the testing set. RJA ability improved more slowly between the ages of 4–7 years old in the ASD group than in the TDC group. In ASD children, RJA ability showed negative correlation with SRS total T-score as well as the scores of five subdomains. Our study provides an automated tool for quantifying RJA and insights for the study of RJA in ASD children, which may help improve ASD screening, subtyping, and behavior interventions.

Generation of non-stabilized β-ester diazos and their applications in carboxylic acid O-H insertion reactions have been reported, which afford β-acyloxy esters in excellent yield. Varieties of aryl- and alkyl-substituted diazos are well tolerated in this insertion reaction under mild and convenient conditions. Moreover, structural modification of the natural product and molecular drug can also be achieved in this reaction. This protocol not only realizes the reaction involving unstable β-ester diazos but also provides an efficient strategy for the synthesis of β-acyloxy esters.

Micro/nanoplastic (MNP) contamination in nonmarine waters has evolved into a notable ecotoxicological threat to the global ecosystem. However, existing strategies for MNP removal are typically limited to chemical flocculation or physical filtering that often fails to decontaminate plastic particulates with ultrasmall sizes or ultralow concentrations. Here, we report a self-driven magnetorobot comprising magnetizable ion-exchange resin sphere that can be used to dynamically remove or separate MNPs from nonmarine waters. As a result of the long-range electrophoretic attraction established by recyclable ion-exchange resin, the magnetorobot shows sustainable removal efficiency of >90% over 100 treatment cycles, with verified broad applicability to varying plastic compositions, sizes, and shapes as well as nonmarine water samples. Our work may facilitate industry-scale MNP removal with affordable cost and minimal secondary pollution and suggests an appealing strategy based on self-propelled micro/nanorobots to sample and assess nanoplastics in aqueous environment.

Melanoma is a high-grade malignant tumor. Melanoma and mole lesions are highly similar and have a very high mortality rate. Early diagnosis and treatment have an important impact on the patient’s condition. The results of dermoscopy are usually judged visually by doctors through long-term clinical experience, and the diagnostic results may be different under different visual conditions. Computer-aided examinations can help doctors improve efficiency and diagnostic accuracy. The purpose of this paper is to use an improved quantum Inception-ResNet-V1 model to classify multiple types of skin lesion images and improve the accuracy of melanoma identification. In this study, the FC layer of Inception-ResNet-V1 is removed, the average pooling layer is the last, SVM is used as the classifier, and the convolutional layer is quantized. The performance of the model was tested experimentally on the ISIC 2019 dataset. To prevent the imbalance of the sample data set from affecting the experiment, the sample data is sampled with weight. Experiments show that the method used shows excellent performance, and the classification accuracy rate reaches 98%, which provides effective help for the clinical diagnosis of melanoma.

Infrared images have good anti-environmental interference ability and can capture hot target information well, but their pictures lack rich detailed texture information and poor contrast. Visible image has clear and detailed texture information, but their imaging process depends more on the environment, and the quality of the environment determines the quality of the visible image. This paper presents an infrared image and visual image fusion algorithm based on deep learning. Two identical feature extractors are used to extract the features of visible and infrared images of different scales, fuse these features through specific fusion methods, and restore the features of visible and infrared images to the pictures through the feature restorer to make up for the deficiencies in the various photos of infrared and visible images. This paper tests infrared visual images, multi-focus images, and other data sets. The traditional image fusion algorithm is compared several with the current advanced image fusion algorithm. The experimental results show that the image fusion method proposed in this paper can keep more feature information of the source image in the fused image, and achieve excellent results in some image evaluation indexes.

Diagnostic tests usually need to operate at a high sensitivity or specificity level in practice. Accordingly, specificity at the controlled sensitivity, or vice versa, is a clinically sensible performance metric for evaluating continuous biomarkers. Meanwhile, the performance of a biomarker may vary across sub-populations as defined by covariates, and covariate-specific evaluation can be informative. In this article, we develop a novel modeling and estimation method for covariate-specific specificity at a controlled sensitivity level. Unlike existing methods which typically adopt elaborate models of covariate effects over the entire biomarker distribution, our approach models covariate effects locally at a specific sensitivity level of interest. We also extend our proposed model to handle the whole continuum of sensitivities via dynamic regression and derive covariate-specific ROC curves. We provide the variance estimation through bootstrapping. The asymptotic properties are established. We conduct extensive simulation studies to evaluate the performance of our proposed methods in comparison with existing methods, and further illustrate the applications in two clinical studies for aggressive prostate cancer.

Single-cell RNA sequencing is becoming an increasingly common tool to investigate the cellular population and patients' outcomes in cancer research. However, due to the sparse data and the complex tumor microenvironment, it is challenging to identify neoplastic cells that play important roles in tumor growth and disease progression. This challenge is exaggerated in the research of blood cancer patients, from whom the neoplastic cells can be highly similar to normal cells. Here, we present partCNV/partCNVH, a statistical framework for rapid and accurate detection of aneuploid cells with local copy number deletion or amplification. Our method uses an expectation–maximization (EM) algorithm with mixtures of Poisson distributions while incorporating cytogenetic information to guide the classification (partCNV). When applicable, we further improve the accuracy by integrating a hidden Markov model for feature selection (partCNVH). We evaluate the performance of the proposed methods using extensive simulation studies and three scRNA-seq datasets from patients with blood cancers. In these applications, our proposed methods demonstrate favorable accuracy and more interpretable results compared with existing methods. In the real data analysis, our results identify many biological processes that have or have not been previously validated, implying multiple biological processes involved in the oncogenesis of myelodysplastic syndromes and acute myeloid leukemia.

National Trail is an integral component of the system of natural reserves. China’s study on the creation of National Trail is scattered and lacks theory and policy at present. Here, the theoretical framework, technical procedure, and construction management of National Trail are examined based on the national conditions of China and the building experience of foreign National Trail. A research framework for National Trail is then established. The research framework encompasses a theoretical framework of policy and related theories, a technical process of analyzing National Trail resource management and public recreation, and construction management, which includes planning and management as well as laws and regulations. This research framework provides a theoretical foundation and policy basis for the future establishment of National Trail as well as general guidance for the planning and design of trails and facilitates the integration of diverse natural space resources.

BackgroundBody mass index (BMI) is a common indicator in clinical practice, but it is not sufficient to predict insulin resistance (IR). Other anthropometric methods supplement BMI in the assessment of body composition, which can be predicted more accurately. This cross-sectional study aimed to evaluate the association between mid-upper arm circumference (MUAC), triceps skinfold (TSF) thickness, mid-arm muscle circumference (MAMC) and IR in Chinese adults.MethodsThis cross-sectional study analyzed data from the 2009 China Health and Nutrition Survey database. The study population was divided into four groups according to the MUAC quartiles, and the homeostasis mode assessment was used to evaluate the degree of IR. Logistic regression analysis was performed to calculate odds ratios (ORs) with 95% confidence intervals (CIs), with adjustments for multiple covariates. Subgroup analyses stratified by age, sex, BMI, waist circumference (WC), smoking status, and alcohol consumption were performed.ResultsIn total, 8,070 participants were included in the analysis. As MUAC increased, BMI, TSF thickness, MAMC, and the proportion of IR tended to increase. However, we found that there was a significant negative association between MUAC and MAMC and IR in the logistic regression analysis, independent of BMI and WC, the ORs for the highest quartiles compared with the lowest quartiles were 0.662 (95%CI: 0.540-0.811) and 0.723 (95%CI: 0.609-0.860), respectively. There was no significant association was observed between the TSF thickness and IR (OR=1.035 [95%CI: 0.870-1.231]). The inverse associations were more pronounced among participants with lower BMI and WC. No significant age-specific differences were observed (P-heterogeneity > 0.05).ConclusionsAfter adjusting for BMI and WC, MUAC was negatively associated with IR in Chinese adults, and the association between MUAC and IR was derived from arm muscle instead of subcutaneous fat. MUAC could be an additional predictor of IR besides BMI and WC in clinical practice.

Heart failure (HF) is considered the clinical endpoint of all cardiovascular diseases (CVDs). Although a large number of HF drugs and therapies have been developed, it is still need to find therapies with better clinical efficacy and fewer side effects. The purpose of this systematic evaluation is to assess the efficacy and safety of Danshen decoction on HF and the improvement of cardiac function (CF).Four databases will be searched to identify any eligible studies, and this protocol does not require ethics committee review as the research is based on published articles. There are no restrictions set for the language, publication date, or status of the study. The clinical effective rate (CER) of HF treatment is considered to be the main result. CF, various serum inflammatory factors, and adverse events were defined as secondary outcomes. When more than 1 article is used to study the changes and results of the same index, we will conduct a meta-analysis. If the heterogeneity is not statistically significant (P .10 or I2 50%), a fixed-effect model will be established to estimate the overall intervention effect. Otherwise, random effect models will be used to provide more conservative results.The results of this meta-analysis will be submitted to a peer-reviewed journal for publication.This study will provide reliable evidence-based basis for the clinical application of Danshen decoction in the treatment of HF.

The study of preimplantation development is of great significance to reproductive biology and regenerative medicine. With the development of high-throughput deep sequencing technology, it has been found that lncRNAs play a very important role in the regulation of embryonic development. In this study, key lncRNAs that regulate embryonic development were screened by analyzing the expression pattern of lncRNAs in porcine in vivo fertilization (IVV) embryos. By knocking down lncRNA expression in in vitro fertilization (IVF) embryos, we investigated its function and mechanism of regulating embryonic development. The results showed that the expression pattern of lncRNA was consistent with the time of gene activation. The lncRNAs were highly expressed in the 4-cell to blastocyst stage but barely expressed in the oocytes and 2-cell stage. So we speculated this part of lncRNAs may regulate gene expression. The lncRNA LOC102165808 (named lncT because the gene near this lncRNA is TFAP2C) was one of them. The knockdown (KD) of lncT inhibited embryonic development, resulting in decreased H3K4me3, H3K4me2, and H3K9me3, and increased DNA methylation. Meanwhile, RNAseq showed SIN3A was the top decreased gene in lncT-KD embryos. There was a severe blastocyst formation defect in SIN3A-KD embryos. Both lncT and SIN3A could affect NANOG and induce more cell apoptosis. In conclusion, the knockdown of lncT inhibits embryonic development by regulating H3K4me3, H3K4me2, DNA methylation, pluripotency gene, and apoptosis, and SIN3A is one of the downstream genes of lncT in regulating embryonic development.

International audience; Agricultural N2O emission is a growing concern for climate change. Recent field evidence suggests that non-growing seasons (NGS) may contribute one-third to half of the annual N2O emissions, but implications on management adaptations remain unclear. Here we used an advanced process-based model, ecosys, to investigate the magnitude and drivers of NGS N2O emissions from the US Midwest. Results showed that simulated NGS N2O emissions accounted for 6–60% of the annual fluxes under continuous corn systems, peaking in counties with NGS precipitation (PNGS) around 300 mm. Divergent patterns of spatial-temporal correlations between NGS N2O emissions and environmental variables were shown in the southeast (PNGS > 300 mm) and the northwest (PNGS < 300 mm) of the study area by simulations. Causal analysis indicates that more intensive freezing caused by decreased air temperature (Ta) is the dominant driver that leads to NGS N2O emissions increasing within the southeast of the study area, while increased PNGS and increased Ta cooperatively result in soil moisture decreasing at soil thaws that enhances NGS N2O production within the northwest of the study area. Scenario simulations suggest that annual N2O emissions in the US Midwest are likely to reduce under climate change primarily due to the reduction of NGS N2O emissions. Our estimates on monetized social benefits inform the necessity to implement spatial-specific mitigation strategies, i.e. determining fertilizer timing and use of nitrification inhibitors (NI). Spring fertilizer application is more beneficial than fall fertilizer application for most counties, however, the latter can bring extra benefits to some counties in the west of the study area. Introducing NI with either spring or fall applications can greatly increase social benefits by reducing N2O emissions and N leaching. This study addresses possibly effective adaptations by providing seasonal- and spatial-explicit mitigation potentials.

A new reactivity mode of tert-butanesulfinamide has been developed, which proceeds through C-S and O-S bond cleavage of N-propargyl tert-butanesulfinylamide allowing rapid assembly of poly functionalized isothiazoles. This intramolecular cyclization reaction could be conducted under mild and convenient conditions and tolerates several fluoroalkyl and substituted phenyl groups with good chemical yields. This reaction not only represents a new reactivity of tert-butanesulfinamide but also provides an easy strategy for the synthesis of isothiazoles.

Fragile X syndrome (FXS) is caused by the loss of fragile X mental retardation protein (FMRP), an RNA-binding protein that can regulate the translation of specific mRNAs. In this study, we developed an FXS human forebrain organoid model and observed that the loss of FMRP led to dysregulated neurogenesis, neuronal maturation and neuronal excitability. Bulk and single-cell gene expression analyses of FXS forebrain organoids revealed that the loss of FMRP altered gene expression in a cell-type-specific manner. The developmental deficits in FXS forebrain organoids could be rescued by inhibiting the phosphoinositide 3-kinase pathway but not the metabotropic glutamate pathway disrupted in the FXS mouse model. We identified a large number of human-specific mRNAs bound by FMRP. One of these human-specific FMRP targets, CHD2, contributed to the altered gene expression in FXS organoids. Collectively, our study revealed molecular, cellular and electrophysiological abnormalities associated with the loss of FMRP during human brain development.

Evidence has demonstrated that miRNAs play an irreplaceable role in tumorigenesis and progression of a broad range of cancers, including gastric cancer. Among these miRNAs, miR-10a and miR-10b have been identified to critically participate in gastric carcinogenesis and malignant progression. In this review, we briefly describe the role of miR-10a and miR-10b in gastric cancer, especially in the regulation of cell proliferation, apoptosis, cell cycle, migration, invasion and metastasis, drug resistance, and cancer stem cells. Furthermore, we highlight several compounds that target the miR-10 family and exhibit antitumor activity in cancer cells. Moreover, we conclude that targeting the miR-10 family might be a promising approach for the treatment of gastric cancer.

The conversion of CO2 driven by solar energy into carbon-containing fuel has huge potential applications. However, most photocatalysts can only promote the two-electron reduction process to generate CO, and it is difficult to produce eight-electron CH4, which is more valuable and can store more solar energy. Herein, we prepared porous silver cyanamide nanocrystals with tunable morphologies via a facile synthesis strategy. Compared with ball/rectangular plate (RAP) and ball/leaf-like plate (SAP), the ball/porous leaf-like plate (LAP) can provide more internal reaction microenvironment, which is not only conducive to the transport of photoinduced charge carriers, but also can expand the active sites for photocatalytic CO2 reduction. Moreover, the suitable band gap of LAP sample can capture more visible light to provide more photoinduced electron-hole pairs to participate in the reduction reaction. Consequently, the LAP sample can convert CO2 to CH4 with remarkable activity and high selectivity (nearly 100%) without cocatalyst and photosensitizer under visible light irradiation. This work provides a promising way to design new photocatalysts for various applications in solar energy conversion.

Free metal particle can affect surface charge accumulation on epoxy insulator installed in gas-insulated transmission line (GIL) or gas-insulated switchgear (GIS), which results in reduction of surface flashover voltage thus threatening the safe operation of the power equipment. This article reports on the charge accumulation behavior on a real size epoxy insulator with bouncing metal particle under DC voltage. A coaxial electrode system was designed for the test under −30 kV, a metal particle-launching system was employed to inject the bouncing linear particle to the insulator surface. The charge distribution was measured by a Kelvin-type probe, and the influence of the particle on the charge accumulation was analyzed with the help of electric field simulation. The results showed that there were mainly two moving patterns of the bouncing particle: the charges were accumulated with speckle shape and the charged particle that hit the edge of electrode had more remarkable influence on the charge accumulation than other particles. It is suggested that the charge distribution feature is dependent upon the collision point and the trajectory of the bouncing particle.

A laboratory scale, 1.0 CMM (m3 min− 1) wet scrubber packed with water-absorbing honeycomb material (HWS) with a very large geometric surface area of 480 m2 m− 3 and a low pressure drop developed in our previous study was shown to achieve a very high removal efficiency for acidic gases but there were no long-term test data. In this study, the HWS scaled up to operate at a 100 CMM flow rate was tested for removing mixed acidic gases at a semiconductor fab for a very long period of 3.5 yr. Results showed that the removal efficiency for the mixed gases emitted from the fab always maintained as high as > 95% for HF, CH3COOH, HCl, HNO3, HNO2, and H2SO4 with the inlet concentrations ranging from supper-ppmv to sub-ppmv, during a 3.5-yr period. With water jet cleaning of the honeycomb modules once per year, the pressure drop of the HWS remained to be low at 0.5–0.8 cm H2O, indicating minimal scaling in the HWS. Additionally, the predicted height and removal efficiencies of the HWS were very close to the experimental data. The excellent long-term performance of the HWS warrants its potential applications in many areas in which liquid absorption is the preferred treatment method and the theoretical equations can facilitate the design of the HWS.

Walnut is a popular nut tree species and usually suffers from drought stress. However, little information is available on the mechanism of walnut responding to drought stress, resulting in lack of basic understanding for its resistance. In order to excavate more functional genes that can respond to stressors, and enrich the theoretical basis for walnut resistance, in this study, 5 MYB genes with complete ORFs were identified from J. regia and the basic bio-information as well as expression patterns in different tissues and response to drought and ABA stresses were confirmed using qRT-PCR assay. The results showed that 2 JrMYB genes belong to R1-MYB subfamily and 3 JrMYBs belong to R2R3-MYB, encoding the proteins from 212 to 362 aa in length. The phylogenetic analysis categorized proteins of 5 JrMYBs and 40 Arabidopsis AtMYBs into 10 subgroups. JrMYBs in the same subgroup exhibited significant similarities in the composition of conserved domains and motifs in amino acid sequences and exon/intron organization in DNA sequences. The results of qRT-PCR analysis revealed that JrMYB genes diversely expressed in various tissues. Moreover, the expression values of JrMYBs were upregulated or downregulated significantly under drought and ABA stresses. Most attractively, in contrast with suffering from drought stress alone, the treatments with drought and additional ABA greatly enhanced the transcript levels of JrMYBs. All these results suggested that JrMYB genes play a vital role in plant biological processes and drought as well as ABA stress response, and possibly perform as ABA-dependent drought response transcription factors in plant.

Summary Correctly annotating individual cell’s type is an important initial step in single-cell RNA sequencing (scRNA-seq) data analysis. Here, we present NeuCA web server, a neural network-based scRNA-seq cell annotation tool with web-app portal and graphical user interface, for automatically assigning cell labels. NeuCA algorithm is accurate and exhaustive, maximizing the usage of measured cells for downstream analysis. NeuCA web server provides over 20 ready-to-use pre-trained classifiers for commonly used tissue types. As the first web-app tool with neural-network infrastructure implemented, NeuCA web will facilitate the research community in analyzing and annotating scRNA-seq data. Availability and implementation NeuCA web server is implemented with R Shiny application online at https://statbioinfo.shinyapps.io/NeuCA/. Supplementary information Supplementary data are available at Bioinformatics online.