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Abstract Using generalizability (G-) theory and qualitative feedback analysis, this study evaluated the role of ChatGPT in enhancing English-as-a-foreign-language (EFL) writing assessments in classroom settings. The primary objectives were to assess the reliability of the holistic scores assigned to EFL essays by ChatGPT versions 3.5 and 4 compared to college English teachers and to evaluate the relevance of the qualitative feedback provided by these versions of ChatGPT. The study analyzed 30 College English Test Band 4 (CET-4) essays written by non-English majors at a university in Beijing, China. ChatGPT versions 3.5 and 4, along with four college English teachers, served as raters. They scored the essays holistically following the CET-4 scoring rubric and also provided qualitative feedback on the language, content, and organization of these essays. The G-theory analysis revealed that the scoring reliability of ChatGPT3.5 was consistently lower than that of the teacher raters; however, ChatGPT4 demonstrated consistently higher reliability coefficients than the teachers. The qualitative feedback analysis indicated that both ChatGPT3.5 and 4 consistently provided more relevant feedback on the EFL essays than the teacher raters. Furthermore, ChatGPT versions 3.5 and 4 were equally relevant across the language, content, and organization aspects of the essays, whereas the teacher raters generally focused more on language but provided less relevant feedback on content and organization. Consequently, ChatGPT versions 3.5 and 4 could be useful AI tools for enhancing EFL writing assessments in classroom settings. The implications of adopting ChatGPT for classroom writing assessments are discussed.

Abstract Background Studies have shown that plant endophytic microbial communities are ubiquitous and closely related to plant growth and health. To clarify the mechanism of the melon varieties with high resistant to wilt, the endophytic microbial compositions and metabolites in roots of melon varieties with high resistant ability to wilt were analyzed. Results The results showed that the abundances of Firmicutes, Ascomycota, Bacillus, Bradyrhizobium, Amycolatopsis, Actinospica, and Catenulispora all increased in roots of wilt high resistant melon varieties (MT) which compared to wilt susceptible melon varieties (MS). Meanwhile, Ochrobactrum, Bordetella, Roseateles, Staphylococcus, Acidovorax, Amycolatopsis, Catenulispora, Promicromonospora, and Gymnopilus were the unique endophytic microbes in roots of MT. Moreover, in comparison with the MS varieties, the functions of Defense mechanisms, Secondary metabolites biosynthesis, transport and catabolism, Nucleotide transport and metabolism, Signal transduction mechanisms, Coenzyme transport and metabolism, Carbohydrate transport and metabolism and Amino acid transport and metabolism all increased in roots of MT varieties. Additionally, the nucleotide metabolism and biosynthesis of cofactors metabolic pathways were also significantly increased in roots of MT varieties. On the other hand, the untargeted metabolome results showed that Biosynthesis of various plant secondary metabolites, Nucleotide metabolism and Biosynthesis of cofactors metabolic pathways were significantly increased in the expression of MT varieties; and the content of metabolic compounds such as flavonoids, Cinnamic acid compounds, Organic acid compounds, and Nucleotides were increased. In addition, the correlation between microbiome and metabolome indicates a significant correlation between the two. Conclusions All above results suggested that higher abundant antagonistic microbes and metabolic functions of endophytes in roots of wilt high resistant melon varieties (MT) were the important mechanisms for their high resistance to wilt. Graphical Abstract

ObjectiveTo evaluate the impact of a health education intervention based on the protection motivation theory (PMT) on the prevention of falls in elderly hospitalized patients with orthostatic hypotension (OH). Methods A total of 400 elderly OH patients aged ≥ 65 years admitted to a tertiary grade A hospital in Nantong city from January 2019 to December 2022 were divided into an intervention group (n = 199) and a control group (n = 201). The control group received routine health education on fall prevention, while the intervention group received an additional health education intervention program based on PMT. The 36-Item Short Form Health Survey (SF-36), the Fall Risk Assessment Scale for the Elderly, and the Balance Test Scale for the Elderly were used to collect information on the two groups' fall risk, balance ability, and quality of life scores of before and 6 months after the intervention. Results The mean age of the 400 patients was 66.53 ± 7.51 years. There were no statistically significant differences in age, sex, education level, occupation, marital status, and monthly income between the intervention and control groups (all P > 0.05). Before the intervention, there were no statistically significant differences in balance test, fall risk assessment and SF-36 scores between the two groups (all P > 0.05). After 6 months of intervention, except for the health change dimension, the SF-36 scores of the intervention group were higher than those of the control group; the balance ability and fall risk scores of the intervention group were lower than those of the control group, and the differences were statistically significant (all P < 0.05). ConclusionThe PMT-based fall prevention health education intervention program can help reduce the risk of falls, improve balance, and improve the quality of life of elderly patients with OH.

Abstract Background The endothelial-to-hematopoietic transition (EHT) process during definitive hematopoiesis is highly conserved in vertebrates. Stage-specific expression of transposable elements (TEs) has been detected during zebrafish EHT and may promote hematopoietic stem cell (HSC) formation by activating inflammatory signaling. However, little is known about how TEs contribute to the EHT process in human and mouse. Results We reconstructed the single-cell EHT trajectories of human and mouse and resolved the dynamic expression patterns of TEs during EHT. Most TEs presented a transient co-upregulation pattern along the conserved EHT trajectories, coinciding with the temporal relaxation of epigenetic silencing systems. TE products can be sensed by multiple pattern recognition receptors, triggering inflammatory signaling to facilitate HSC emergence. Interestingly, we observed that hypoxia-related signals were enriched in cells with higher TE expression. Furthermore, we constructed the hematopoietic cis-regulatory network of accessible TEs and identified potential TE-derived enhancers that may boost the expression of specific EHT marker genes. Conclusions Our study provides a systematic vision of how TEs are dynamically controlled to promote the hematopoietic fate decisions through transcriptional and cis-regulatory networks, and pre-train the immunity of nascent HSCs.

BackgroundDiabetic foot ulcers (DFU) are a major complication associated with significant morbidity and mortality. While numerous studies have investigated risk factors for these ulcers in general, few have focused specifically on patients with Neurovascular Complications of Diabetes. This study aimed to evaluate the prevalence and risk factors for DFU in this specific population.MethodsWe analyzed data from the National Institutes of Health (NIS) database for the years 2017-2019, involving a cohort of 161,834 patients aged over 18 who were diagnosed with neurovascular complications of diabetes. Demographic characteristics (age, gender, ethnicity), hospital characteristics, comorbidities, and other relevant data were included for analysis. A binary logistic regression model was generated to identify independent risk factors for DFU.ResultsThe prevalence of DFU among patients with neurovascular complications of diabetes was 29.4% during the period from 2017 to 2019. Compared to patients without DFU, those with DFU had longer hospitalization times and higher costs. The multiple regression analysis revealed that Iron-deficiency anemia (OR, 1.10; 95% CI, 1.01-1.11; P=0.019), Hypertension (OR, 1.07; 95% CI, 1.03-1.11; P=0.001), Obesity (OR, 1.08; 95% CI, 1.06-1.11; P

Based on the objective evaluation of the regional ecological quality (Urban Cluster in Mid-inner Zhejiang) by Remote Sensing based Ecological Index (RSEI), it was proposed to study the spatial-temporal response of the regional ecological quality to the urban built-up areas, impervious surface, land use and “production-living-ecological” space under urban settlement change to quantitatively describe the mechanism of human activities’ influence on the regional ecology. The results showed that: (1) From 1985 to 2020, the RSEI of the Urban Cluster in Mid-inner Zhejiang was above 0.50 as a whole, showing a trend of first decreasing and then increasing with a slight decrease in some parts. (2) From the perspective of the urban built-up areas, it was dominated by ecological level 2–3, gradually changing from ecological level 3 to ecological level 2. (3) From the perspective of the impervious surface, it was dominated by ecological level 2–3, accounting for more than 75.00% of the total study area. (4) From the perspective of land use, the cropland, forestland, water and construction land were mainly ecological level 2–4, 3–4, 3–4 and 2–3. (5) From the perspective of “production-living-ecological” space, production space, ecological space and living space were dominated by ecological level 3, 3–4 and 2–3. The results can deepen the understanding of the impact of urban settlement development on the regional ecological quality, avoid the unbalanced situation of blindly pursuing socio-economic development while ignoring the ecological environment, which scientifically helps the sustainable construction and high-quality development of the Urban Cluster in Mid-inner Zhejiang.

Abstract Resistance to chemotherapy remains a formidable obstacle in acute myeloid leukemia (AML) therapeutic management, necessitating the exploration of optimal strategies to maximize therapeutic benefits. Venetoclax with 3+7 daunorubicin and cytarabine (DAV regimen) in young adult de novo AML patients is evaluated. 90% of treated patients achieved complete remission, underscoring the potential of this regimen as a compelling therapeutic intervention. To elucidate underlying mechanisms governing response to DAV in AML, quantitative phosphoproteomics to discern distinct molecular signatures characterizing a subset of DAV‐sensitive patients is used. Cluster analysis reveals an enrichment of phosphoproteins implicated in chromatin organization and RNA processing within DAV‐susceptible and DA‐resistant AML patients. Furthermore, kinase activity profiling identifies AURKB as a candidate indicator of DAV regimen efficacy in DA‐resistant AML due to AURKB activation. Intriguingly, AML cells overexpressing AURKB exhibit attenuated MCL‐1 expression, rendering them receptive to DAV treatment and maintaining them resistant to DA treatment. Moreover, the dataset delineates a shared kinase, AKT1, associated with DAV response. Notably, AKT1 inhibition augments the antileukemic efficacy of DAV treatment in AML. Overall, this phosphoproteomic study identifies the role of AURKB as a predictive biomarker for DA, but not DAV, resistance and proposes a promising strategy to counteract therapy resistance in AML.

Abstract Using generalizability (G-) theory as a theoretical framework and research methodology, this study examined the impact of the current one-rater holistic scoring practice on the rater variability and reliability of constructed response questions in New York State high-stakes tests of grades four and six English language arts (ELA) and grades four and five mathematics assessments. Following the New York State scoring rubrics, a total of 36 grades four and six ELA constructed response samples and 72 grades four and five mathematics constructed response samples were marked holistically by ten independent raters having current certifications as educators in the State of New York. The results indicated that the current single-rater holistic scoring practice would not be able to yield acceptable G-coefficients for the New York State grades four and six ELA and grades four and five mathematics assessments. Implications for assessment policy making at the local and state levels are discussed.

The exacerbation of safety risk levels in metro deep foundation pit construction is attributed to the interactive coupling of numerous risk factors. To comprehensively explore the underlying mechanisms of safety incidents, complex network theory is applied to analyze interactions among risk factors systemically. Initially, through the identification of safety risk factors, a risk factor system comprising six primary risk factors and 35 secondary risk factors is established. Subsequently, by utilizing coupling mechanism analysis and complex network theory, a coupling network model of safety risks in metro deep foundation pit construction with 42 nodes and 184 directed edges is constructed, with network topology indicators analysis revealing the evolutionary law of risk coupling. Finally, Python software is employed to simulate the network with single-node, random, and targeted immunization. Key risk factor nodes are identified using network efficiency measurement methods. The results indicate that all risk factors positively influence the connectivity of the coupling network, and the risk-coupling network presents small-world and scale-free characteristics. In comparison with different immunization strategies, targeted immunization is found to be more effective than random immunization, and prioritizing the control of risk factors with a high degree of centrality, such as “violation of operating regulations” and “inadequate safety supervision and hidden danger inspection”, proves more effective in alleviating risk coupling, underscoring the importance of prioritizing control of key risk nodes in the network. These findings provide a scientific basis for risk management and optimization in metro deep foundation pit construction.

Abstract Using the research ethics scale (Huang et al., 2021) and follow-up interviews, this study examined Chinese social sciences graduate students’ understanding of research ethics of empirical studies involving human subjects. The participants included 463 Chinese graduate students majoring in teacher education, English education, management, and economics. The quantitative findings suggested that these graduate students had a fairly good understanding of researchers’ ethical responsibilities and developed general human subjects’ ethical awareness; furthermore, there existed significant research experience and gender-by-research experience interaction effects on their understanding of researchers’ ethical responsibilities and human subjects’ ethical awareness, respectively. The qualitative results indicated that the participants had realized the importance of ethics reviews for social sciences research including human subjects; and they identified best ways to promote research ethics education for social sciences graduate students in Chinese higher education. Implications for Chinese university leaders, program developers, and research methods professors are discussed.

Abstract Despite advances in cancer treatment, immune checkpoint blockade (ICB) only achieves complete response in some patients, illustrating the need to identify resistance mechanisms. Using an ICB-insensitive tumor model, here we discover cisplatin enhances the anti-tumor effect of PD-L1 blockade and upregulates the expression of Ariadne RBR E3 ubiquitin-protein ligase 1 (ARIH1) in tumors. Arih1 overexpression promotes cytotoxic T cell infiltration, inhibits tumor growth, and potentiates PD-L1 blockade. ARIH1 mediates ubiquitination and degradation of DNA-PKcs to trigger activation of the STING pathway, which is blocked by the phospho-mimetic mutant T68E/S213D of cGAS protein. Using a high-throughput drug screen, we further identify that ACY738, less cytotoxic than cisplatin, effectively upregulates ARIH1 and activates STING signaling, sensitizing tumors to PD-L1 blockade. Our findings delineate a mechanism that tumors mediate ICB resistance through the loss of ARIH1 and ARIH1-DNA-PKcs-STING signaling and indicate that activating ARIH1 is an effective strategy to improve the efficacy of cancer immunotherapy.

Abstract Objective The coronavirus disease-19 (COVID-19) pandemic restricts rapid implementation of in-person delivery of cardiac rehabilitation (CR) at the center for coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI), thus enabling a cohort comparison of in-person vs. remote CR program. This study aims to investigate outcomes of exercise capacity, health-related quality of life (HRQL), mental health, and family burden of stable CAD patients undergoing PCI in low-to-moderate risk after different delivery models of CR program. Methods The study included a cohort of stable CAD patients undergoing PCI who had experienced two naturally occurring modes of CR program after hospital discharge at two time periods, January 2019 to December 2019 (in-person CR program) and May 2020 to May 2021 (remote CR program). The exercise capacity was assessed by means of 6-min walk test (6MWT), maximal oxygen uptake (VO2max) and the respiratory anaerobic threshold (VO2AT) before discharge, at the end of the 8-week and 12-week in-person or remote CR program after discharge. Results No adverse events occurred during the CR period. CAD patients had a longer distance walked in 6 min with a higher VO2max after 8-week and 12-week CR program whether in-person or remote model (p

Abstract The use of whole‐genome sequence (WGS) data is expected to improve genomic prediction (GP) power of complex traits because it may contain mutations that in strong linkage disequilibrium pattern with causal mutations. However, a few previous studies have shown no or small improvement in prediction accuracy using WGS data. Incorporating prior biological information into GP seems to be an attractive strategy that might improve prediction accuracy. In this study, a total of 6334 pigs were genotyped using 50K chips and subsequently imputed to the WGS level. This cohort includes two prior discovery populations that comprise 294 Landrace pigs and 186 Duroc pigs, as well as two validation populations that consist of 3770 American Duroc pigs and 2084 Canadian Duroc pigs. Then we used annotation information and genome‐wide association study (GWAS) from the WGS data to make GP for six growth traits in two Duroc pig populations. Based on variant annotation, we partitioned different genomic classes, such as intron, intergenic, and untranslated regions, for imputed WGS data. Based on GWAS results of WGS data, we obtained trait‐associated single‐nucleotide polymorphisms (SNPs). We then applied the genomic feature best linear unbiased prediction (GFBLUP) and genomic best linear unbiased prediction (GBLUP) models to estimate the genomic estimated breeding values for growth traits with these different variant panels, including six genomic classes and trait‐associated SNPs. Compared with 50K chip data, GBLUP with imputed WGS data had no increase in prediction accuracy. Using only annotations resulted in no increase in prediction accuracy compared to GBLUP with 50K, but adding annotation information into the GFBLUP model with imputed WGS data could improve the prediction accuracy with increases of 0.00%–2.82%. In conclusion, a GFBLUP model that incorporated prior biological information might increase the advantage of using imputed WGS data for GP.

Fruit shape is an important character of watermelon. And the compositions of rhizospheric and endophytic microorganisms of watermelon with different fruit shape also remains unclear. To elucidate the biological mechanism of watermelon fruit shape formations, the rhizospheric and endophytic microbial community compositions between oval (OW) and circular watermelons (CW) were analyzed. The results showed that except of the rhizospheric bacterial richness (P < 0.05), the rhizospheric and endophytic microbial (bacterial and fungal) diversity were not statistically significant between OW and CW (P > 0.05). However, the endophytic microbial (bacterial and fungal) compositions were significantly different. Firstly, Bacillus, Rhodanobacter, Cupriavidus, Luteimonas, and Devosia were the unique soil dominant bacterial genera in rhizospheres of circular watermelon (CW); In contrast, Nocardioides, Ensifer, and Saccharomonospora were the special soil dominant bacterial genera in rhizospheres of oval watermelons (OW); Meanwhile, Cephalotrichum, Neocosmospora, Phialosimplex, and Papulaspora were the unique soil dominant fungal genera in rhizospheres of circular watermelon (CW); By contrast, Acremonium, Cladosporium, Cryptococcus_f__Tremellaceae, Sodiomyces, Microascus, Conocybe, Sporidiobolus, and Acremonium were the unique soil dominant fungal genera in rhizospheres of oval watermelons (OW). Additionally, Lechevalieria, Pseudorhodoferax, Pseudomonas, Massilia, Flavobacterium, Aeromicrobium, Stenotrophomonas, Pseudonocardia, Novosphingobium, Melittangium, and Herpetosiphon were the unique dominant endophytic bacterial genera in stems of CW; In contrast, Falsirhodobacter, Kocuria, and Kineosporia were the special dominant endophytic genera in stems of OW; Moreover, Lectera and Fusarium were the unique dominant endophytic fungal genera in stems of CW; By contrast, Cercospora only was the special dominant endophytic fungal genus in stems of OW. All above results suggested that watermelons with different fruit shapes exactly recruited various microorganisms in rhizospheres and stems. Meanwhile, the enrichments of the different rhizosphric and endophytic microorganisms could be speculated in relating to watermelon fruit shapes formation.

This study examined Chinese EFL researchers’ English abstract writing in language education. Using open-ended questionnaires, it first investigated 24 Chinese EFL researchers’ perceptions of their challenges in writing English abstracts. Using generalizability theory and follow-up interviews, it then invited 16 experienced English journal reviewers to assess 27 published English abstracts written by Chinese EFL researchers to identify common errors and suggest improvement tips. Finally, it examined eight selected Chinese EFL researchers’ critical reflections on the English journal reviewers’ assessment of the 27 English abstracts. The results indicated that Chinese EFL researchers experienced several challenges in writing English abstracts. Further, the English reviewers’ assessment of the 27 abstracts was consistent and reliable. The common errors were associated with the accuracy, non-evaluative nature, coherence and readability, and conciseness of an English abstract. The English reviewers provided tips for improvement, and Chinese EFL researchers expressed their critical reflections on their assessment. Educational implications are discussed.

Summary: While a few works have shown that Mettl3 plays oncogenic roles in hepatocellular carcinoma (HCC), its function in early HCC tumorigenesis remains unclear. In Mettl3flox/flox; Alb-Cre knockout mice, Mettl3 loss leads to aberrant hepatocyte homeostasis and liver damage. Importantly, Mettl3 deletion dramatically accelerates liver tumorigenesis in various HCC mouse models. Depletion of Mettl3 in adult Mettl3flox/flox mice through TBG-Cre administration also enhances liver tumor development, while overexpression of Mettl3 inhibits hepatocarcinogenesis. Mechanistically, aggravated tumorigenesis upon Mettl3 deletion is a consequence of hepatocyte dedifferentiation and hyperproliferation via m6A-mediated modulation on Hnf4α and cell cycle genes. In contrast, by using Mettl3flox/flox; Ubc-Cre mice, depletion of Mettl3 in established HCC ameliorates tumor progression. Additionally, Mettl3 is overexpressed in HCC tumors compared with adjacent non-tumor tissues. The present findings define a tumor-suppressive role of Mettl3 in liver tumorigenesis, indicating its potentially opposite stage-dependent functions in HCC initiation versus progression.

RNA-binding proteins (RBP) have emerged as essential regulators that control gene expression and modulate multiple cancer traits. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy derived from transformation of T-cell progenitors that normally undergo discrete steps of differentiation in the thymus. The implications of essential RBP during T-cell neoplastic transformation remain largely unclear. Systematic evaluation of RBP identifies RNA helicase DHX15, which facilitates the disassembly of the spliceosome and release of lariat introns, as a T-ALL dependency factor. Functional analysis using multiple murine T-ALL models demonstrates the essential importance of DHX15 in tumor cell survival and leukemogenesis. Moreover, single-cell transcriptomics reveals that DHX15 depletion in T-cell progenitors hinders burst proliferation during the transition from doublenegative to double-positive cells (CD4-CD8- to CD4+CD8+). Mechanistically, abrogation of DHX15 perturbs RNA splicing and leads to diminished levels of SLC7A6 and SLC38A5 transcripts due to intron retention, thereby suppressing glutamine import and mTORC1 activity. We further propose a DHX15 signature modulator drug ciclopirox and demonstrate that it has prominent anti-T-ALL efficacy. Collectively, our data highlight the functional contribution of DHX15 to leukemogenesis through regulation of established oncogenic pathways. These findings also suggest a promising therapeutic approach, i.e., splicing perturbation by targeting spliceosome disassembly, may achieve considerable anti-tumor efficacy.

Abstract Background The differential signaling and outcome of patients with p190 or p210 transcripts of BCR-ABL1 have been systematically investigated in chronic myeloid leukemia rather than in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Methods We analyzed the outcomes and ABL1 mutation profiles in 305 consecutive adult patients with Ph+ ALL treated with chemotherapy plus tyrosine kinase inhibitors. We also studied transcriptome features in two newly diagnosed patients with p190 and p210 using single-cell RNA sequencing (scRNA-seq). Results P190 and p210 were found in 199 (65%) and 106 (35%) patients, respectively. Compared to patients with p190, a higher white blood cell count (p = 0.05), platelet count (p = 0.047), BCR-ABL1 transcript level (p

ABSTRACT To elucidate the biological mechanism of formation of the netted pattern in melons, the characteristics of the soil bacterial community structure in the rhizosphere and of the endophytic bacteria in the stems of netted melons were analyzed. High-throughput sequencing technology was used for the analysis of plant stem and soil samples collected from netted melons (NM) and oriental melons (OM). At the phylum level, Acidobacteria, Dependentiae, and Chloroflexi were the dominant endophytic bacteria in the stems of NM only. In addition, at the genus level, the soil bacteria enriched in the rhizospheres of NM and OM were different. Five unique dominant bacterial genera, including Gaiella, Actinoplanes, norank_f__Gemmatimonadaceae, Devosia, and Bradyrhizobium, were the dominant soil bacteria unique to the rhizosphere of NM. In contrast, Mycobacterium and unclassified_f__Acetobacteraceae were the dominant soil bacteria in the rhizosphere of OM. Moreover, Hyphomicrobium, Nocardioides, norank_f__norank_o__Gaiellales, Bryobacter, unclassified_f__Pseudonocardiaceae, Pseudolabrys, norank_f__Micropepsaceae, Ideonella, Mizugakiibacter, norank_f__Vermiphilaceae, unclassified_f__Xanthobacteraceae, Bacillus, and Pseudaminobacter were the dominant endophytic bacteria in the stems of NM. In contrast, Flavobacterium, Stenotrophomonas, unclassified_f__Burkholderiaceae, Paenibacillus, Bordetella, Hephaestia, and Ideonella were the dominant endophytic bacteria in the stems of OM. The specific substances (enzymes, proteins, endogenous hormones, etc.) secreted by unique rhizospheric and endophytic bacteria, such as Bacillus and Bradyrhizobium, may activate the promoters of genes. Therefore, the expression of genes can be regulated by unique rhizospheric and endophytic bacteria for formation or nonformation of netting in melons. IMPORTANCE The study of the differential structures and functions of rhizospheric and endophytic bacterial communities between netted melon and oriental melon treatments is investigated. Our findings make a significant contribution to the literature because they are the first step in coupling the study of rhizospheric and endophytic microbial community structure to reticulation formation in netted melon. Further, we believe that this research appears to be meaningful because it provides new insights into the mechanisms of reticulation formation in netted melon in modern agricultural production.

IntroductionHighly accomplished doctoral students may suffer when they cannot manage their performance due to the crippling effects of anxiety and stress. This is even more likely to occur in the highly charged setting of competitive research. Using a structural equation modeling approach, this study examined how anxiety and stress impact the performance of Chinese doctoral students through self-regulated learning.MethodsA total of 491 doctoral students and recent completers representing 112 universities in China participated in this study. A 42-item five-point Likert scale survey was used to measure participants’ perceived anxiety (emotional and physical reactions), stress (study- and research-related stress), self-regulated learning, and performance (task and contextual performance) in their doctoral studies. Specifically, the extent to which participants’ self-regulated learning mediated the influence of anxiety and stress on their task performance and contextual performance in their doctoral studies, as well as significant structural equation modeling differences across demographic variables of gender (i.e., male versus female), major (i.e., arts versus sciences), status (i.e., individuals pursuing a doctoral degree versus recent completers), and age (i.e., 30 and younger versus over 30) were examined.Results and DiscussionThe results indicated that self-regulated learning considerably affected task and contextual performance; stress had a considerable direct effect on task and contextual performance; the indirect influence of stress on task and contextual performance via self-regulated learning was significant; and there was a significant structural equation modeling difference between arts and sciences doctoral students. Educational implications are discussed.

Abstract Dynamic‐responsive self‐assembly is the process of ordered supramolecular structure formation or reversible decomposition from building blocks. This process is driven by non‐covalent interactions based on complex stimulus‐responsive systems comprising different components within a microenvironment. Furthermore, stimuli‐responsive assembly‐disassembly is an intrinsic interaction process in organisms, indispensable in maintaining life activities and functions. However, the dynamic interactions between dynamically responsive nano‐drug systems (DRNSs) and biological systems remain unpredictable, which are a challenge for the precisely targeted therapy and controlled drug release of DRNSs in vivo. This review highlights novel self‐assembling peptide‐based nano‐drug systems and their biological interactions. By precisely controlling the shape and size of self‐assembled peptide nanomaterials, biologically simulated components with diverse biological functions and precise transport at the subcellular level can be achieved. We have also summarized the limitations and challenges of responsive self‐assembling peptide nanomaterials in clinical translation. Additionally, we have discussed the future perspectives of supramolecular therapeutics using signaling molecule gradient concentrations and efficiencies and highlighted the direction for developing clinically translatable smart nanomedicines.

Abstract As a potential biodegradable implant material, zinc (Zn) alloys have attracted increasing attention due to their good biocompatibility and moderate degradation rate. Zn and its alloys are expected to become candidate materials for medical devices. The metals implanted in the human body will inevitably undergo friction in the human body before it is completely degraded. Friction and wear are essential factors which may cause medical devices’ service failure. However, there are still few studies on the friction and wear properties of biodegradable Zn-based alloys in the human body, and most studies just focus on the mechanical properties, degradation properties and biocompatibility of the alloys. Thus, it is crucial to study the friction and wear properties of Zn and its alloys. In the present work, we investigated the tribological properties of biodegradable pure Zn and Zn-X (Li, Cu, Ge) alloys. Our study found that under simulated body fluid and dry friction conditions, the addition of alloying elements Li and Cu can improve the friction properties of Zn. Among the four metals, Zn-0.5Li alloy has the lowest friction coefficient and the best wear resistance. Hank’s solution has lubricating and corrosive effects. That is to say, when the alloy is rubbed in Hank’s solution, it can not only be protected by the lubrication of the solution, but also tribocorrosion will occur as well.

IntroductionThis mixed-methods national study has a two-fold purpose: (a) to invite Chinese college students to rate their overall difficulties in the eight areas of English learning, i.e., listening, speaking, reading, writing, pronunciation, grammar, vocabulary, and culture; and (b) to invite them to identify their key challenges in learning EFL. Specifically, the following three research questions were asked: (a) what are their overall difficulties in the eight areas of learning EFL? (b) Are there significant differences in rating their overall difficulties in these eight areas across the demographic variables of gender (i.e., male versus female participants) and subject discipline (arts versus sciences versus English subject disciplines participants)? And (c) what are their key challenges in learning EFL?MethodsThe participants included a sample of 1,525 freshmen and sophomore students currently studying at seven universities across China. The instrument was a survey that consisted of a five-point Likert scale self-evaluation form and a major essay question addressing their key challenges. The qualitative data can help to probe deeply into the research setting to obtain in-depth understandings about Chinese college students’ English learning; and therefore, they can greatly enhance the quantitative data.Results and discussionThe quantitative results indicated that listening, speaking, and writing were their three key difficult areas in EFL learning; further, students’ subject discipline (arts versus sciences verse English subject disciplines) had significant effects on their perceived learning challenges in English listening and vocabulary. The qualitative results confirmed that listening, speaking, and writing were their three key challenging areas. Their specific learning challenges in each area were examined. Implications for Chinese college English teachers and administrators are discussed in terms of pedagogy and policy making, respectively.

IntroductionThis study examined the significant differences in Chinese college students’ learning perceptions and outcomes between the “quasi smart” and smart classrooms under the perspective of the community of inquiry (CoI) framework.MethodsThe participants were 275 freshmen students who took the “college physics” hybrid course in the spring of 2022 at a four-year university in central China. Data were collected from the CoI survey, a follow-up focus group interview with ten randomly selected student participants, and a semi-structured interview with the instructor.Results and discussionThe results indicated that the students’ perceptions of the teaching, social, and cognitive presences were significantly higher in the smart classroom than in the “quasi smart” classroom; further, students in the smart classroom achieved significantly higher course marks than those in the “quasi smart” classroom. The pros and cons of these two different classroom environments were identified by the participating students and their course instructor.

Abstract Background Abnormal alternative splicing is frequently associated with carcinogenesis. In B‐cell acute lymphoblastic leukemia (B‐ALL), double homeobox 4 fused with immunoglobulin heavy chain (DUX4/IGH) can lead to the aberrant production of E‐26 transformation‐specific family related gene abnormal transcript (ERGalt) and other splicing variants. However, the molecular mechanism underpinning this process remains elusive. Here, we aimed to know how DUX4/IGH triggers abnormal splicing in leukemia. Methods The differential intron retention analysis was conducted to identify novel DUX4/IGH‐driven splicing in B‐ALL patients. X‐ray crystallography, small angle X‐ray scattering (SAXS), and analytical ultracentrifugation were used to investigate how DUX4/IGH recognize double DUX4 responsive element (DRE)‐DRE sites. The ERGalt biogenesis and B‐cell differentiation assays were performed to characterize the DUX4/IGH crosslinking activity. To check whether recombination‐activating gene 1/2 (RAG1/2) was required for DUX4/IGH‐driven splicing, the proximity ligation assay, co‐immunoprecipitation, mammalian two hybrid characterizations, in vitro RAG1/2 cleavage, and shRNA knock‐down assays were performed. Results We reported previously unrecognized intron retention events in C‐type lectin domain family 12, member A abnormal transcript (CLEC12Aalt) and chromosome 6 open reading frame 89 abnormal transcript (C6orf89alt), where also harbored repetitive DRE‐DRE sites. Supportively, X‐ray crystallography and SAXS characterization revealed that DUX4 homeobox domain (HD)1‐HD2 might dimerize into a dumbbell‐shape trans configuration to crosslink two adjacent DRE sites. Impaired DUX4/IGH‐mediated crosslinking abolishes ERGalt, CLEC12Aalt, and C6orf89alt biogenesis, resulting in marked alleviation of its inhibitory effect on B‐cell differentiation. Furthermore, we also observed a rare RAG1/2‐mediated recombination signal sequence‐like DNA edition in DUX4/IGH target genes. Supportively, shRNA knock‐down of RAG1/2 in leukemic Reh cells consistently impaired the biogenesis of ERGalt, CLEC12Aalt, and C6orf89alt. Conclusions All these results suggest that DUX4/IGH‐driven DNA crosslinking is required for RAG1/2 recruitment onto the double tandem DRE‐DRE sites, catalyzing V(D)J‐like recombination and oncogenic splicing in acute lymphoblastic leukemia.

Using student and teacher open-ended questionnaires, and interviews with teachers and school principals and administrators, this study examined the bilingual learning difficulties faced by the Tibetan minority students in Qinghai Province, China, the challenges in meeting their needs, and the suggestions for coping with these challenges. The participants included 200 Tibetan minority students, 20 classroom teachers, and 10 school principals and administrators randomly selected from eight secondary schools located in eight different counties, where there are the most Tibetan minority students in Qinghai Province. The results showed that they experienced considerable difficulties in both spoken and written Chinese, which had prevented them from understanding the lectures, answering questions, interacting with peers in the classroom, and communicating with friends and classmates outside of classroom. The challenges in meeting their bilingual learning needs include: (a) a language choice dilemma for parents, (b) insufficient training of bilingual education teachers, (c) lack of bilingual education resources; (d) short of qualified teachers; (e) lack of parent-school communication; and (f) insufficient training of principals and administrators. Suggestions for coping with these challenges and educational implications are discussed.

Abstract One challenge facing omics association studies is the loss of statistical power when adjusting for confounders and multiple testing. The traditional statistical procedure involves fitting a confounder-adjusted regression model for each omics feature, followed by multiple testing correction. Here we show that the traditional procedure is not optimal and present a new approach, 2dFDR, a two-dimensional false discovery rate control procedure, for powerful confounder adjustment in multiple testing. Through extensive evaluation, we demonstrate that 2dFDR is more powerful than the traditional procedure, and in the presence of strong confounding and weak signals, the power improvement could be more than 100%.

The findings of a quantitative study about Chinese consumers regarding how cultural values, environmental awareness, and perceived consumer effectiveness (PCE) influence their green purchase intentions are presented in this article. This study aimed to explain these crucial factors’ direct and indirect effects on green purchases and the impact of cultural values and environmental awareness on PCE. Specifically, a conceptual model was suggested and empirically tested using survey information gathered from 371 customers from China, and the SmartPLS-SEM approach was applied. The results indicated that PCE significantly influences consumers’ intentions to make green purchases, and through environmental awareness and PCE, cultural values, directly and indirectly, influence Chinese consumers’ green buying intentions. This study offers novel perspectives on consumer behavior for purchasing environment-friendly products.

Abstract Background The rapidly increasing dimensionality and throughput of flow and mass cytometry data necessitate new bioinformatics tools for analysis and interpretation, and the recently emerging single-cell-based algorithms provide a powerful strategy to meet this challenge. Results Here, we present CytoTree, an R/Bioconductor package designed to analyze and interpret multidimensional flow and mass cytometry data. CytoTree provides multiple computational functionalities that integrate most of the commonly used techniques in unsupervised clustering and dimensionality reduction and, more importantly, support the construction of a tree-shaped trajectory based on the minimum spanning tree algorithm. A graph-based algorithm is also implemented to estimate the pseudotime and infer intermediate-state cells. We apply CytoTree to several examples of mass cytometry and time-course flow cytometry data on heterogeneity-based cytology and differentiation/reprogramming experiments to illustrate the practical utility achieved in a fast and convenient manner. Conclusions CytoTree represents a versatile tool for analyzing multidimensional flow and mass cytometry data and to producing heuristic results for trajectory construction and pseudotime estimation in an integrated workflow.

Phytosynthesis of silver nanoparticles (Ag NPs) has been progressively acquiring attractiveness. In this study, the root of Zanthoxylum nitidum was used to synthesize Ag NPs, and its pre-emergence herbicidal activity was tested. The synthesized Ag NPs by the aqueous extract from Z. nitidum were characterized by visual inspection, ultraviolet-visible spectroscopy, dynamic light scattering (DLS), X-ray diffraction (XRD), transmission electron microscopy (TEM), and energy dispersive X-ray spectroscopy (EDX). The plant-mediated synthesis was completed within 180 min and the Ag NPs exhibited a characteristic peak at around 445 nm. The results of the DLS measurement showed that the average hydrodynamic diameter was 96 nm with a polydispersity index (PDI) of 0.232. XRD results indicated the crystalline nature of the phytogenic Ag NPs. A TEM analysis revealed that the nanoparticles were spherical with an average particle size of 17 nm. An EDX spectrum confirmed the presence of an elemental silver signal. Furthermore, the Ag NPs exhibited a herbicidal potential against the seed germination and seedling growth of Bidens Pilosa L. The present work indicates that Ag NPs synthesized by plant extract could have potential for the development of a new nanoherbicide for weed prevention and control.

Runs of homozygosity (ROH) and heterozygosity (ROHet) are windows into population demographic history and adaptive evolution. Numerous studies have shown that deleterious mutations are enriched in the ROH of humans, pigs, cattle, and chickens. However, the relationship of deleterious variants to ROH and the pattern of ROHet in goats have been largely understudied. Here, 240 Guangfeng and Ganxi goats from Jiangxi Province, China, were genotyped using the Illumina GoatSNP50 BeadChip and genome-wide ROH, ROHet, and genetic load analyses were performed in the context of 32 global goat breeds. The classes with the highest percentage of ROH and ROHet were 0.5–2 Mb and 0.5–1 Mb, respectively. The results of inbreeding coefficients (based on SNP and ROH) and ROHet measurements showed that Guangfeng goats had higher genetic variability than most Chinese goats, while Ganxi goats had a high degree of inbreeding, even exceeding that of commercial goat breeds. Next, the predicted damaging homozygotes were more enriched in long ROHs, especially in Guangfeng goats. Therefore, we suggest that information on damaging alleles should also be incorporated into the design of breeding and conservation programs. A list of genes related to fecundity, growth, and environmental adaptation were identified in the ROH hotspots of two Jiangxi goats. A sense-related ROH hotspot (chromosome 12: 50.55–50.81 Mb) was shared across global goat breeds and may have undergone selection prior to goat domestication. Furthermore, an identical ROHet hotspot (chromosome 1: 132.21–132.54 Mb) containing two genes associated with embryonic development (STAG1 and PCCB) was detected in domestic goat breeds worldwide. Tajima’s D and BetaScan2 statistics indicated that this region may be caused by long-term balancing selection. These findings not only provide guidance for the design of conservation strategies for Jiangxi goat breeds but also enrich our understanding of the adaptive evolution of goats.

Summary: Background: Systemic Lupus Erythematosus (SLE) is a complex and heterogeneous autoimmune disease mediated by quantities of autoantibodies in which anti-double-stranded DNA (anti-dsDNA) antibodies are important. Besides, glycosylation is one of the most commonly post-translational modifications of antibodies. The association of anti-dsDNA antibodies glycosylation and SLE disease activity is still unknown. Methods: We enrolled 101 consecutive treatment-naïve SLE patients with positive anti-dsDNA antibodies from the Department of Rheumatology and Immunology at Ruijin Hospital, Shanghai, between 2017 and 2019. Serum samples were used in this study. We analysed the glycosylation of anti-dsDNA IgG and total IgG subclasses according to systemic lupus erythematosus disease activity index (SLEDAI) scores. Statistical analysis and machine learning were performed to assess the correlation between glycosylation of anti-dsDNA IgG and total IgG with disease activity. Findings: Serum samples from 86 patients could be detected with anti-dsDNA IgG glycopeptide and subclass of IgG glycoform. Cluster analysis showed that glycosylation of anti-dsDNA IgG and total IgG subclasses were different in SLE patients. Fucosylation, galactosylation, and sialylation levels of anti-dsDNA IgG1 were increased with SLEDAI scores (all p

Runs of homozygosity (ROH) are widely used to investigate genetic diversity, demographic history, and positive selection signatures of livestock. Commercial breeds provide excellent materials to reveal the landscape of ROH shaped during the intense selection process. Here, we used the GeneSeek Porcine 50K single-nucleotide polymorphism (SNP) Chip data of 3,770 American Duroc (AD) and 2,096 Canadian Duroc (CD) pigs to analyze the genome-wide ROH. First, we showed that AD had a moderate genetic differentiation with CD pigs, and AD had more abundant genetic diversity and significantly lower level of inbreeding than CD pigs. In addition, sows had larger levels of homozygosity than boars in AD pigs. These differences may be caused by differences in the selective intensity. Next, ROH hotspots revealed that many candidate genes are putatively under selection for growth, sperm, and muscle development in two lines. Population-specific ROHs inferred that AD pigs may have a special selection for female reproduction, while CD pigs may have a special selection for immunity. Moreover, in the overlapping ROH hotspots of two Duroc populations, we observed a missense mutation (rs81216249) located in the growth and fat deposition-related supergene (ARSB-DMGDH-BHMT) region. The derived allele of this variant originated from European pigs and was nearly fixed in Duroc pigs. Further selective sweep and association analyses indicated that this supergene was subjected to strong selection and probably contributed to the improvement of body weight and length in Duroc pigs. These findings will enhance our understanding of ROH patterns in different Duroc lines and provide promising trait-related genes and a functional-altering marker that can be used for genetic improvement of pigs.

Abstract Background A virus community is the spectrum of viral strains populating an infected host, which plays a key role in pathogenesis and therapy response in viral infectious diseases. However automatic and dedicated pipeline for interpreting virus community sequencing data has not been developed yet. Results We developed Quasispecies Analysis Package (QAP), an integrated software platform to address the problems associated with making biological interpretations from massive viral population sequencing data. QAP provides quantitative insight into virus ecology by first introducing the definition “virus OTU” and supports a wide range of viral community analyses and results visualizations. Various forms of QAP were developed in consideration of broader users, including a command line, a graphical user interface and a web server. Utilities of QAP were thoroughly evaluated with high-throughput sequencing data from hepatitis B virus, hepatitis C virus, influenza virus and human immunodeficiency virus, and the results showed highly accurate viral quasispecies characteristics related to biological phenotypes. Conclusions QAP provides a complete solution for virus community high throughput sequencing data analysis, and it would facilitate the easy analysis of virus quasispecies in clinical applications.

Abstract Background Epigenome-wide association studies (EWAS), which seek the association between epigenetic marks and an outcome or exposure, involve multiple hypothesis testing. False discovery rate (FDR) control has been widely used for multiple testing correction. However, traditional FDR control methods do not use auxiliary covariates, and they could be less powerful if the covariates could inform the likelihood of the null hypothesis. Recently, many covariate-adaptive FDR control methods have been developed, but application of these methods to EWAS data has not yet been explored. It is not clear whether these methods can significantly improve detection power, and if so, which covariates are more relevant for EWAS data. Results In this study, we evaluate the performance of five covariate-adaptive FDR control methods with EWAS-related covariates using simulated as well as real EWAS datasets. We develop an omnibus test to assess the informativeness of the covariates. We find that statistical covariates are generally more informative than biological covariates, and the covariates of methylation mean and variance are almost universally informative. In contrast, the informativeness of biological covariates depends on specific datasets. We show that the independent hypothesis weighting (IHW) and covariate adaptive multiple testing (CAMT) method are overall more powerful, especially for sparse signals, and could improve the detection power by a median of 25% and 68% on real datasets, compared to the ST procedure. We further validate the findings in various biological contexts. Conclusions Covariate-adaptive FDR control methods with informative covariates can significantly increase the detection power for EWAS. For sparse signals, IHW and CAMT are recommended.

Abstract An outbreak of clusters of viral pneumonia due to a novel coronavirus (2019-nCoV/SARS-CoV-2) happened in Wuhan, Hubei Province in China in December 2019. Since the outbreak, several groups reported estimated R 0 of Coronavirus Disease 2019 (COVID-19) and generated valuable prediction for the early phase of this outbreak. After implementation of strict prevention and control measures in China, new estimation is needed. An infectious disease dynamics SEIR (Susceptible, Exposed, Infectious, and Removed) model was applied to estimate the epidemic trend in Wuhan, China under two assumptions of R t . In the first assumption, R t was assumed to maintain over 1. The estimated number of infections would continue to increase throughout February without any indication of dropping with R t = 1.9, 2.6, or 3.1. The number of infections would reach 11,044, 70,258, and 227,989, respectively, by 29 February 2020. In the second assumption, R t was assumed to gradually decrease at different phases from high level of transmission (R t = 3.1, 2.6, and 1.9) to below 1 (R t = 0.9 or 0.5) owing to increasingly implemented public health intervention. Several phases were divided by the dates when various levels of prevention and control measures were taken in effect in Wuhan. The estimated number of infections would reach the peak in late February, which is 58,077–84,520 or 55,869–81,393. Whether or not the peak of the number of infections would occur in February 2020 may be an important index for evaluating the sufficiency of the current measures taken in China. Regardless of the occurrence of the peak, the currently strict measures in Wuhan should be continuously implemented and necessary strict public health measures should be applied in other locations in China with high number of COVID-19 cases, in order to reduce R t to an ideal level and control the infection.

Heterozygosity can effectively reflect the diverse models of population structure and demographic history. However, the genomic distribution of heterozygotes and the correlation between regions of heterozygosity (runs of heterozygosity, ROHet) and phenotypes are largely understudied in livestock. The objective of this study was to identify ROHet in the Duroc pig genome, and investigate the relationships between ROHet and eight important economic traits. Here, we genotyped 3,770 American Duroc (S21) and 2,096 Canadian Duroc (S22) pigs using 50 K single nucleotide polymorphism array to analyze heterozygosity. A total of 145,010 and 84,396 ROHets were characterized for S21 and S22 populations, respectively. ROHet segments were mostly enriched in 1–2 Mb length classification (75.48% in S21 and 72.25% in S22). The average genome length covered by ROHet was 66.53 ± 12.20 Mb in S21 and 73.32 ± 13.77 Mb in S22 pigs. Additionally, we detected 20 and 13 ROHet islands in S21 and S22 pigs. Genes in these genomic regions were mainly involved in the biological processes of immunity and reproduction. Finally, the genome-wide ROHet-phenotypes association analysis revealed that 130 ROHets of S21 and 84 ROHets of S22 were significantly associated with eight economic traits. Among the candidate genes in the significant ROHet regions, 16 genes related to growth, metabolism, and meat quality were considered as candidate genes for important economic traits of pigs. This work preliminarily explores the effect of heterozygosity-rich regions in the pig genome on production performance and provides new insights for subsequent research on pig genetic improvement.

This mixed-methods study examined the impact of the COVID-19 pandemic on 1493 Grades 7, 8, and 9 students’ self-perceived emotional states in Wuhan, China when it was locked down for the pandemic on January 23, 2020 and when the lockdown was lifted on April 8, 2020, as well as the changes of their emotional states over the 1-year period after the lockdown was lifted. A five-point Likert scale survey was administered to the participants between March 1 and April 1, 2020 when Wuhan was blocked down; and three focus group interviews were conducted between May 1 and May 31, 2021, 1 year after the lockdown was lifted. The results showed that these students in Wuhan experienced feelings of loss of control and negative emotions when the city was locked down and they were home quarantined; furthermore, there were significant differences for their self-perceived feelings of loss of control and negative emotions across demographic variables of gender, grade level, physical activity, social economic status, and family cohesion; finally, their emotional states changed substantially at different time nodes during this pandemic. Implications for students, parents, and schools are discussed.

The clinical and molecular characteristics of localized diffuse large B-cell lymphoma (DLBCL) with single nodal (SN) or single extranodal (SE) involvement remain largely elusive in the rituximab era. The clinical data of 181 patients from a retrospective cohort and 108 patients from a phase 3 randomized trial NHL-001 (NCT01852435) were reviewed. Meanwhile, genetic aberrations, gene expression pattern, and tumor immunophenotype profile were revealed by DNA and RNA sequencing of 116 and 53 patients, respectively. SE patients showed similar clinicopathological features as SN patients, except for an increased percentage of low-intermediate risk in the National Comprehensive Cancer Network–International Prognostic Index. According to the molecular features, increased MPEG1 mutations were observed in SN patients, while SE patients were associated with upregulation of TGF-β signaling pathway and downregulation of T-cell receptor signaling pathway. SE patients also presented immunosuppressive status with lower activity of killing of cancer cells and recruiting dendritic cells. Extranodal involvement had no influence on progression-free survival (PFS) or overall survival (OS) in localized DLBCL. Serum lactate dehydrogenase >3 upper limit of normal was an independent adverse prognostic factor for OS, and ATM mutations were related to inferior PFS. Although the overall prognosis is satisfactory, specific clinical, genetic, and microenvironmental factors should be considered for future personalized treatment in localized DLBCL.

Habitat quality is the key to regional ecological restoration and green development, and land use change is an essential factor affecting habitat quality. Studying the spatial and temporal evolution characteristics of land use change and habitat quality under multiple scenarios is significant for regional ecological restoration and management, and for preventing future ecological and environmental risks. We used the improved Logistic-CA-Markov (Logistic-Cellular Automata-Markov) and InVEST (Integrated Valuation of Ecosystem Services and Trade-offs) models to establish the spatial patterns of habitat quality in the Yellow River Basin from 2000 to 2040 and analyzed the characteristics of land use and habitat quality changes under scenarios of natural development (S1), ecological protection (S2), and urban expansion (S3). The results showed that in 2000, 2005, 2010, 2015, and 2020, the main land use types in the watershed were dryland and grassland, accounting for more than 72%. Paddy land, dryland, woodland, middle-coverage grassland, and unused land all showed decreasing trends, whereas all other land types showed increasing trends. Influenced by human activities and the environment, the watershed habitat quality was low, with 80% of the areas with middle to low grades, but the overall trend was rising. The spatial variability in habitat quality of the watershed was significant, with habitat quality improvements in the central and northern regions and continued deterioration around the cities in the southern and western parts. The spatial autocorrelation and aggregation of habitat quality in the watershed were strong, and future land use patterns in the study area had a significant relationship with human activities. Simulation of future scenarios revealed ecological conservation catalytic effects on habitat quality in the study area, whereas urban expansion deteriorated watershed habitat quality. This study could provide support for future ecological conservation decisions.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

In China, there are so many patients go to the highest-level hospitals to get medical treatment directly, it is essential to study how to guide patients to take the initiative to go to the basic medical institutions first in most cases. The information asymmetry theory and the game model are applied for rational analysis in this paper. We construct two models, a doctor-patient signaling game model to study the dynamic process of patients who seek medical treatment to hospitals that are trustworthy, and a two-level treatment game model to study how to achieve a hierarchical diagnosis and reasonable referral in the case of different types of patients (general and serious conditions), considering the knowledge spillover variables supported by big data to analyze the changes in the total utility of the medical market, hospitals, and patients. With the first model analysis, it points out that only when there are three preconditions, namely, high disguising cost, controlling the income of diagnosis and treatment, and reducing the losses caused by untrustworthy behaviors, can trust signals play a real role and achieve the coordination of the optimal market type. In addition to the second model analysis, it is found that the hierarchical medical system with optimizing the allocation of medical resources has a positive effect on the benefit of the medical system and the improvement of the total welfare of patients. It also shows that the full application of big data system can further enhance the total benefit of the medical system under this system. This paper gives management suggestions for strengthening information transmission, rational design of communication system, promotion and application of big data intelligent diagnosis, and treatment for medical management departments and medical institutions at all levels to make decisions.

B cell precursor acute lymphoblastic leukemia (BCP-ALL) is a blood cancer that originates from the abnormal proliferation of B-lymphoid progenitors. Cell population components and cell–cell interaction in the bone marrow microenvironment are significant factors for progression, relapse, and therapy resistance of BCP-ALL. In this study, we identified specifically expressed genes in B cells and myeloid cells by analyzing single-cell RNA sequencing data for seven BCP-ALL samples and four healthy samples obtained from a public database. Integrating 1356 bulk RNA sequencing samples from a public database and our previous study, we found a total of 57 significant ligand–receptor pairs (24 upregulated and 33 downregulated) in the autocrine crosstalk network of B cells. Via assessment of the communication between B cells and myeloid cells, another 29 ligand–receptor pairs were discovered, some of which notably affected survival outcomes. A score-based model was constructed with least absolute shrinkage and selection operator (LASSO) using these ligand–receptor pairs. Patients with higher scores had poorer prognoses. This model can be applied to create predictions for both pediatric and adult BCP-ALL patients.

Therapeutic agents for refractory prolactinomas that are resistant to dopamine agonists (DAs) are troublesome, and surgery often only removes a large part of the tumor without complete remission. Among the various second-line treatment regimens, the treatment effect of the alkylating agent temozolomide (TMZ) is only effective for approximately half of patients; however, complete remission is rare. Here we report a patient with prolactinoma who was resistant to high-dose cabergoline (CAB) treatment, demonstrating a continuous increase in both the tumor volume and the prolactin (PRL) level. Given that this case is a refractory prolactinoma, the patient underwent two transsphenoidal approach (TSA) surgeries. The pathological analysis indicated that the Ki-67 index increased significantly from 3% to 30%, and the expression levels of DRD2 and MGMT were low. Finally, TMZ treatment was recommended. A total of six cycles of TMZ standard chemotherapy shrank the tumor volume and the tumor disappeared completely. During the 6-month follow-up period, the tumor did not relapse again, and the PRL level was also normal. RNA sequencing and DNA whole genome sequencing were performed on this prolactinoma specimen, revealing 16 possible gene mutations, including a missense mutation of the PABPC1 gene. Additionally, the copy number variation analysis results showed that several chromosomes had copy number gains compared to the matched peripheral blood sample. In this case, low expression of DRD2 and high proliferation led to resistance to CAB, whereas low MGMT expression contributed to sensitivity to TMZ treatment. The results of genome sequencing still need further investigation at the molecular level to explain the tumor aggressiveness and high sensitivity to TMZ.

Behavioral strategies used in scent communication can reflect the adaptive capacity of animals. Signal detection theory and the principle of least effort posit that scent marking must be efficient and energy maximizing. The giant panda (Ailuropoda melanoleuca) is a solitary species that relies heavily on scent communication. There have been few studies on scent communication of wild pandas due to their elusive nature. To deepen the understanding of scent communication in this vulnerable species, we analyze a novel dataset obtained from integrating transect surveys on scent marked trees with infrared camera trapping of wild giant pandas performing scent marking and scent investigation behaviors. We found that pandas selected large coniferous trees for scent marking relative to what was available. Of the scent marked trees, trees that were more frequently marked than others were those of preferred species, high elevation, at topographical aspects conducive for odor transmission, with larger surrounding trees, and at gentle slopes. There were three peaks in the frequency of scent communication throughout the year in October, December, and March, the third period overlapping with the mating season. Scent communication occurred mainly during daytime hours, peaking at dusk (18:00–20:00). Frequency of anogenital gland secretion (AGS) markings were significantly greater than urine markings during the mating season but not during other times of year, which may reflect their stronger capacity to convey estrus state of females during mating season. The findings enrich the understanding of giant panda scent communication, and more broadly emphasize the importance of considering scent communication for conservation efforts such as corridor design for this vulnerable species.

Abstract Generation of hematopoietic stem/progenitor cells (HSPCs) via cell expansion or cell reprogramming has been widely achieved by overexpression of transcription factors. Herein, it is reported that without introducing exogenous genes, mouse fibroblasts can be reprogrammed into hemogenic cells based on lineage tracing analysis, which further develop into hematopoietic cells, by treatment of cocktails of chemical compounds. The chemical cocktails also reprogram differentiated hematopoietic cells back into HSPC‐like cells. Most importantly, the chemical cocktails enabling hematopoietic reprogramming robustly promote HSPC proliferation ex vivo. The expanded HSPCs acquire enhanced capacity of hematopoietic reconstruction in vivo. Single‐cell sequencing analysis verifies the expansion of HSPCs and the cell reprogramming toward potential generation of HSPCs at the same time by the chemical cocktail treatment. Thus, the proof‐of‐concept findings not only demonstrate that hematopoietic reprogramming can be achieved by chemical compounds but also provide a promising strategy for acquisition of HSPCs by chemical cocktail‐enabled double effects.

Abstract Background One problem that plagues epigenome-wide association studies is the potential confounding due to cell mixtures when purified target cells are not available. Reference-free adjustment of cell mixtures has become increasingly popular due to its flexibility and simplicity. However, existing methods are still not optimal: increased false positive rates and reduced statistical power have been observed in many scenarios. Methods We develop SmartSVA, an optimized surrogate variable analysis (SVA) method, for fast and robust reference-free adjustment of cell mixtures. SmartSVA corrects the limitation of traditional SVA under highly confounded scenarios by imposing an explicit convergence criterion and improves the computational efficiency for large datasets. Results Compared to traditional SVA, SmartSVA achieves an order-of-magnitude speedup and better false positive control. It protects the signals when capturing the cell mixtures, resulting in significant power increase while controlling for false positives. Through extensive simulations and real data applications, we demonstrate a better performance of SmartSVA than the existing methods. Conclusions SmartSVA is a fast and robust method for reference-free adjustment of cell mixtures for epigenome-wide association studies. As a general method, SmartSVA can be applied to other genomic studies to capture unknown sources of variability.

Chronic lymphocytic leukemia is a highly inheritable cancer. Here the authors conduct a metaanalysis of four genome-wide association studies and identify three novel loci located near EOMES, SERPINB6 and LPPassociated with risk of this disease.

The increase in bioinformatics resources such as tools/scripts and databases poses a great challenge for users seeking to construct interactive and reproducible biological data analysis applications. Here, we propose an open-source, comprehensive, flexible R package named BioInstaller that consists of the R functions, Shiny application, the HTTP representational state transfer application programming interfaces, and a docker image. BioInstaller can be used to collect, manage and share various types of bioinformatics resources and perform interactive and reproducible data analyses based on the extendible Shiny application with Tom’s Obvious, Minimal Language and SQLite format databases. The source code of BioInstaller is freely available at our lab website, http://bioinfo.rjh.com.cn/labs/jhuang/tools/bioinstaller, the popular package host GitHub, https://github.com/JhuangLab/BioInstaller, and the Comprehensive R Archive Network, https://CRAN.R-project.org/package=BioInstaller. In addition, a docker image can be downloaded from DockerHub (https://hub.docker.com/r/bioinstaller/bioinstaller).